FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bystrom, J Dyer, KD Ravin, SSTD Naumann, N Stephany, DA Foster, PS Wynn, TA Rosenberg, HF AF Bystrom, Jonas Dyer, Kimberly D. Ting-De Ravin, Suk See Naumann, Nora Stephany, David A. Foster, Paul S. Wynn, Thomas A. Rosenberg, Helene F. TI Interleukin-5 does not influence differential transcription of transmembrane and soluble isoforms of IL-5R alpha in vivo SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE granulocytes; hematopoiesis; interleukin-5 ID RECEPTOR-ALPHA-CHAIN; HUMAN IL-5 RECEPTOR; MESSENGER-RNA; ANGIOSTRONGYLUS-CANTONENSIS; ANTISENSE OLIGONUCLEOTIDE; MOLECULAR-CLONING; SUBUNIT GENE; IN-VITRO; EXPRESSION; EOSINOPHILIA AB Interleukin-5 (IL-5) promotes signal transduction and expansion of eosinophil colonies in bone marrow via interactions with its heterodimeric receptor (IL-5R). Two variants encoding soluble forms of the alpha subunit (sIL-5R alpha) have been described, although the signals promoting and/or limiting differential transcription remain to be clarified. Objectives: Our intent was to explore the role of IL-5 in regulating differential transcription of these splice variants in vivo. Methods: We have designed a quantitative reverse transcriptase-polymerase chain reaction assay to detect transcripts encoding the transmembrane, soluble 1 and 2 forms of IL-5R alpha in two strains of wild-type (BALB/c and C57BL/6) and corresponding IL-5 gene-deleted mice. Wild-type mice respond to S. mansoni infection with a gradual increase in serum IL-5 and eosinophilia, which is not observed in IL-5 gene-deleted mice. Results and conclusions: We find that IL-5 is not necessary for differential splicing to occur in vivo, as all three forms of the IL-5R alpha are detected in both strains of IL-5 gene-deleted mice, with ratios of transcript expression (transmembrane : soluble 1 : soluble 2) that were indistinguishable from their wild-type counterparts. Differential splicing does vary markedly between strains, potentially because of local effects of strain-specific polymorphisms. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Flow Cytometry Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Newcastle, Newcastle, NSW 2308, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; Foster, Paul/G-5057-2013 FU Intramural NIH HHS NR 42 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD SEP PY 2006 VL 77 IS 3 BP 181 EP 190 DI 10.1111/j.1600-0609.2006.00699.x PG 10 WC Hematology SC Hematology GA 070HB UT WOS:000239510800001 PM 16856933 ER PT J AU Doan, BQ Sorant, AJM Frangakis, CE Bailey-Wilson, JE Shugart, YY AF Doan, Betty Q. Sorant, Alexa J. M. Frangakis, Constantine E. Bailey-Wilson, Joan E. Shugart, Yin Y. TI Covariate-based linkage analysis: application of a propensity score as the single covariate consistently improves power to detect linkage SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE covariate; affected relative pairs; linkage analysis; simulation; propensity score; LODPAL ID RELATIVE-PAIR LINKAGE; GENETIC-HETEROGENEITY; GENOME SCAN; LOCUS; MODEL AB Successful identification of genetic risk loci for complex diseases has relied on the ability to minimize disease and genetic heterogeneity to increase the power to detect linkage. One means to account for disease heterogeneity is by incorporating covariate data. However, the inclusion of each covariate will add one degree of freedom to the allele sharing based linkage test, which may in fact decrease power. We explore the application of a propensity score, which is typically used in causal inference to combine multiple covariates into a single variable, as a means of allowing for multiple covariates with the addition of only one degree of freedom. In this study, binary trait data, simulated under various models involving genetic and environmental effects, were analyzed using a nonparametric linkage statistic implemented in LODPAL. Power and type I error rates were evaluated. Results suggest that the use of the propensity score to combine multiple covariates as a single covariate consistently improves the power compared to an analysis including no covariates, each covariate individually, or all covariates simultaneously. Type I error rates were inflated for analyses with covariates and increased with increasing number of covariates, but reduced to nominal rates with sample sizes of 1000 families. Therefore, we recommend using the propensity score as a single covariate in the linkage analysis of a trait suspected to be influenced by multiple covariates because of its potential to increase the power to detect linkage, while controlling for the increase in the type I error. C1 Johns Hopkins Bloomberg Sch Pub Hlth, Dept Epidemiol, Baltimore, MD USA. NHGRI, NIH, Stat Genet Sect, Inherited Dis Res Branch, Baltimore, MD USA. NHGRI, NIH, Genometr Sect, Inherited Dis Res Branch, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Doan, BQ (reprint author), Johns Hopkins Sch Med, Inst Med Genet, Broadway Res Bldg,733 N Broadway,Room 572, Baltimore, MD 21205 USA. EM bdoan@jhmi.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [RR03655] NR 24 TC 5 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD SEP PY 2006 VL 14 IS 9 BP 1018 EP 1026 DI 10.1038/sj.ejhg.5201650 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 076ZG UT WOS:000239996600008 PM 16736037 ER PT J AU Gadoth, N Slor, H Avraham, D Orgal, S Kraemer, KH AF Gadoth, N. Slor, H. Avraham, D. Orgal, S. Kraemer, K. H. TI A familial adult onset dementia-spinocerebellar complex due to a new mutation in the XPF DNA repair gene SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 Meir Hosp, Dept Neurol, Kefar Sava, Israel. Tel Aviv Univ, Dept Human Genet, IL-69978 Tel Aviv, Israel. Meir Hosp, Dept Dermatol, Kefar Sava, Israel. Natl Canc Inst, Basic Res Lab, Ctr Canc Res, Bethesda, MD USA. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2006 VL 13 SU 2 BP 41 EP 41 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 084HE UT WOS:000240523200132 ER PT J AU Muraro, PA AF Muraro, P. A. TI Reconstitution of the immune repertoire and immune tolerance after HSCT SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2006 VL 13 SU 2 BP 307 EP 308 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 084HE UT WOS:000240523200992 ER PT J AU Windels, F Kiyatkin, EA AF Windels, Francois Kiyatkin, Eugene A. TI Dopamine action in the substantia nigra pars reticulata: iontophoretic studies in awake, unrestrained rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dendritic release; freely moving rats; iontophoresis; presynaptic modulation; single-unit recording ID STRIATAL NEURONAL-ACTIVITY; GAMMA-AMINOBUTYRIC-ACID; VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; BASAL GANGLIA; IMMUNOCYTOCHEMICAL LOCALIZATION; GLUTAMATE RECEPTORS; SUBTHALAMIC NUCLEUS; BEHAVING RATS AB Dopamine (DA) neurons located in the substantia nigra pars compacta release DA not only via axonal terminals, affecting neurotransmission within the striatum, but also via dendrites, some of which densely protrude into the substantia nigra pars reticulata (SNr). Although the interaction of dendritically released DA with somatodendritic autoreceptors regulates DA cell activity, released DA may also affect SNr neurons. These cells, however, lack postsynaptic DA receptors, making it unclear how locally released DA modulates their activity. Although previous work in brain slices suggests that DA might modulate the activity of GABA inputs, thus affecting SNr neurons indirectly, it remains unclear how increased or decreased DA release might affect these cells exposed to normal afferent inputs. To explore this issue, we examined the effects of iontophoretic DA and amphetamine on SNr neurons in awake, unrestrained rats. DA had no consistent effects on SNr cells but amphetamine, known to induce DA release, dose-dependently inhibited most of them. This effect was blocked by SCH23390, a selective D1 receptor blocker, which itself strongly increased neuronal discharge rate. As GABA input is a major factor regulating the activity of SNr neurons, our data suggest that dendritically released DA, by interacting with D1 receptors on striato-nigral and pallido-nigral afferents, is able to decrease this input, thus releasing SNr neurons from tonic, GABA-mediated inhibition. Surprisingly, a full DA receptor blockade (SCH23390 + eticlopride) did not result in the expected increase in SNr discharge rate, suggesting that other mechanisms are responsible for behavioral abnormalities following acute disruption of DA transmission. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov RI Windels, Francois/G-5432-2010 FU Intramural NIH HHS NR 62 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2006 VL 24 IS 5 BP 1385 EP 1394 DI 10.1111/j.1460-9568.2006.05015.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 084XG UT WOS:000240567100016 PM 16987223 ER PT J AU Cravens, CJ Vargas-Pinto, N Christian, KM Nakazawa, K AF Cravens, Catherine J. Vargas-Pinto, Noelia Christian, Kimberly M. Nakazawa, Kazu TI CA3 NMDA receptors are crucial for rapid and automatic representation of context memory SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE avoidance learning; conditioning; fear; hippocampus; knockout mouse ID SHOCK FREEZING DEFICIT; HIPPOCAMPAL-LESIONS; DORSAL HIPPOCAMPUS; LATENT INHIBITION; CONJUNCTIVE REPRESENTATIONS; DEFENSIVE REACTIONS; EPISODIC MEMORY; SPATIAL MEMORY; FEAR; RATS AB It is argued that the hippocampus contributes to acquisition of context-specific memory although neural mechanisms have not been clarified. To evaluate the role of CA3 in context-specific memory, we developed one-trial context discrimination tasks to test acquisition and retrieval of contextual memory in CA3 pyramidal cell-restricted N-methyl-d-aspartate (NMDA) receptor knockout mice. Mutants were unable to discriminate conditioned and no-shock contexts 3 h after one-trial avoidance training. These phenotypes were not evident 24 h after one-trial training or 3 h after multi-trial training. Following one-trial contextual fear conditioning, mutants showed a selective deficit in context discrimination during a retention test 3 h after acquisition, although overall freezing levels were similar to those of the control mice. As in the avoidance task, this context discrimination impairment was not observed 24 h after initial conditioning. Interestingly, extending the post-shock period to 3 min during the one-trial fear conditioning task eliminated the discrimination deficit observed at the 3 h retention interval. These results suggest that: (i) impaired rapid context discrimination during the recall test is dependent on the duration of post-shock period during conditioning; (ii) CA3 NMDA receptors are critically involved in rapid and automatic formation of a unified context memory representation from the sensory information; (iii) CA3 NMDA receptors support contextual pattern separation; (iv) fear memory to foot-shock is acquired without CA3 NMDA receptors. It appears that rapid and automatic context memory representations from one-time experience are mediated, at least in part, by CA3 NMDA receptors. C1 NIMH, Unit Genet Cognit & Behav, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RP Nakazawa, K (reprint author), NIMH, Unit Genet Cognit & Behav, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. EM nakazawk@mail.nih.gov RI Nakazawa, Kazutoshi/J-6195-2015 OI Nakazawa, Kazutoshi/0000-0001-5699-9093 FU Intramural NIH HHS NR 60 TC 36 Z9 36 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 2006 VL 24 IS 6 BP 1771 EP 1780 DI 10.1111/j.1460-9568.2006.05044.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 086GC UT WOS:000240660800027 PM 17004940 ER PT J AU Mamede, M Abreu-E-Lima, P Gandler, W Nose, V Gerbaudo, VH AF Mamede, M. Abreu-e-Lima, P. Gandler, W. Nose, V. Gerbaudo, V. H. TI Estimation of esophageal tumor length by FDG-PET with surgical pathology confirmation: relationship to metabolic tumor volume SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Natl Inst Hlth, Ctr Informat Technol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2006 VL 33 SU 2 BP S165 EP S165 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V43XI UT WOS:000202967400390 ER PT J AU Schou, M Zoghbi, SS Shetty, H Shchukin, E Liow, J Hong, J Andree, A Gulyas, B Farde, L Innis, RB Pike, VW Halldin, C AF Schou, M. Zoghbi, S. S. Shetty, H. Shchukin, E. Liow, J. Hong, J. Andree, A. Gulyas, B. Farde, L. Innis, R. B. Pike, V. W. Halldin, C. TI Investigation of the metabolites of (S, S)-[11C] MeNER in humans, monkeys and rats SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract C1 Karolinska Inst, Stockholm, Sweden. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD SEP PY 2006 VL 33 SU 2 BP S212 EP S212 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V43XI UT WOS:000202967400609 ER PT J AU Salihu, HM Emusu, D Sharma, PP Aliyu, ZY Oyelese, Y Druschel, CM Kirby, RS AF Salihu, Hamisu M. Emusu, Donath Sharma, Puza P. Aliyu, Zakari Y. Oyelese, Yinka Druschel, Charlotte M. Kirby, Russell S. TI Parity effect on preterm birth and growth outcomes among infants with isolated omphalocele SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY LA English DT Article DE omphalocele; fetal morbidity; nulliparity; multiparity ID ABDOMINAL-WALL DEFECTS; GASTROSCHISIS; RISK AB Objective: To assess the association between parity and fetal morbidity outcomes among omphalocele-affected fetuses. Study design: We carried out a retrospective study of 498 cases of isolated omphalocele (210 born to nulliparous and 288 to multiparous mothers) in New York State from 1983 through 1999. Infants of nulliparous mothers were compared to those of multiparous gravidas using adjusted odds ratios generated from a logistic regression. Results: Omphalocele-affected fetuses of nulliparous mothers had a lower risk of being delivered preterm (odds ratio (OR) = 0.49; 95% CI = 0.27-0.90) but comparable risks for low birth weight (OR = 1.01; 95% CI = 0.60-1.72), very low birth weight (OR = 0.33; 95% CI = 0.09-1.20), very preterm birth (OR = 0.42; 95% CI = 0.15-1.16), and small size for gestational age (SGA) [OR = 0.61; 95% CI = 0.23-1.63]. Conclusion: Omphalocele-affected fetuses of multiparous mothers have double the risk for preterm birth compared to their nulliparous counterparts. This information is potentially useful in counseling parents whose fetuses have omphaloceles. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, New Brunswick, NJ 08901 USA. Univ Alabama, Dept Maternal & Child Hlth, Birmingham, AL USA. NIH, Bethesda, MD 20892 USA. New York State Dept Hlth, Congenital Malformat Registry, Troy, NY USA. RP Salihu, HM (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, 125 Paterson St, New Brunswick, NJ 08901 USA. EM hsalihu@uab.edu NR 16 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0301-2115 J9 EUR J OBSTET GYN R B JI Eur. J. Obstet. Gynecol. Reprod. Biol. PD SEP-OCT PY 2006 VL 128 IS 1-2 BP 91 EP 96 DI 10.1016/j.ejogrb.2005.11.009 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 089VI UT WOS:000240909100017 PM 16337727 ER PT J AU Lieberman, JA Stroup, TS McEvoy, JP Swartz, MS Keefe, R Perkins, DO Davis, S Davis, CE Lebowitz, B Hsiao, J AF Lieberman, J. A. Stroup, T. S. McEvoy, J. P. Swartz, M. S. Keefe, R. Perkins, D. O. Davis, S. Davis, C. E. Lebowitz, B. Hsiao, J. TI CATIE trial results SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol ID CHRONIC-SCHIZOPHRENIA; RISPERIDONE; OLANZAPINE; QUETIAPINE C1 Columbia Univ, New York, NY USA. Univ N Carolina, Durham, NC USA. Duke Univ, Durham, NC 27706 USA. Yale Univ, New Haven, CT 06520 USA. NIMH, NIH, Bethesda, MD 20892 USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S184 EP S185 DI 10.1016/S0924-977X(06)70072-4 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771300062 ER PT J AU Pezawas, LP Goldman, AL Verchinski, BA Mattay, VA Callicott, JH Kolachana, BS Straub, RE Egan, MF Meyer-Lindenberg, A Weinberger, DR AF Pezawas, L. P. Goldman, A. L. Verchinski, B. A. Mattay, V. A. Callicott, J. H. Kolachana, B. S. Straub, R. E. Egan, M. F. Meyer-Lindenberg, A. Weinberger, D. R. TI Biologic epistasis between SERT and BDNF: complex genetic mechanisms of depression SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol ID VAL66MET POLYMORPHISM C1 Med Univ Vienna, Dept Gen Psychiat, Vienna, Austria. NIMH, NIH, GCAP, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S310 EP S311 DI 10.1016/S0924-977X(06)70331-5 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771300321 ER PT J AU Rapoport, J AF Rapoport, J. TI Very early onset schizophrenia SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 NIH, Child Psychiat Branch, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S196 EP S197 DI 10.1016/S0924-977X(06)70108-0 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771300098 ER PT J AU Vitiello, B AF Vitiello, B. TI Is there place for pharmacology in the treatment of childhood anxiety disorders? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 19th Congress of the European-College-of-Neuropsychopharmacology CY SEP 16-20, 2006 CL Paris, FRANCE SP European Coll Neuropsychopharmacol C1 NIMH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2006 VL 16 SU 4 BP S190 EP S190 DI 10.1016/S0924-977X(06)70087-6 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 087VQ UT WOS:000240771300077 ER PT J AU Murta-Nascimento, C Real, FX Kogevinas, M Garcia-Closas, M Rothman, N Lloreta, J Tardon, A Serra, C Dosemeci, M Silverman, D Carrato, A Malats, N AF Murta-Nascimento, C. Real, F. X. Kogevinas, M. Garcia-Closas, M. Rothman, N. Lloreta, J. Tardon, A. Serra, C. Dosemeci, M. Silverman, D. Carrato, A. Malats, N. TI N-acetyl transferase and glutathione S-transferase genetic variants and outcome of bladder cancer SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 CREAL, IMIM, Barcelona, Spain. URBCM, IMIM, Barcelona, Spain. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. Hosp del Mar, Barcelona, Spain. Univ Oviedo, Oviedo, Spain. Univ Pompeu Fabra, Barcelona, Spain. Hosp Univ Elche, Serv Oncol Med, Elche, Spain. RI Murta-Nascimento, Cristiane/G-3738-2012; Serra, C/E-6879-2014; Lloreta, J/I-2112-2014; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; Lloreta, J/0000-0003-1644-9470; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD SEP PY 2006 VL 5 IS 14 MA 73 BP 805 EP 805 DI 10.1016/S1569-9056(06)61323-7 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 085TW UT WOS:000240628300074 ER PT J AU Laureti, P Moret, L Zhang, YC Yu, YK AF Laureti, P. Moret, L. Zhang, Y. -C. Yu, Y. -K. TI Information filtering via iterative refinement SO EUROPHYSICS LETTERS LA English DT Article ID COMPLEX NETWORKS; SYSTEMS AB With the explosive growth of accessible information, expecially on the Internet, evaluation-based filtering has become a crucial task. Various systems have been devised aiming to sort through large volumes of information and select what is likely to be more relevant. In this letter we analyse a new ranking method, where the reputation of information providers is determined self-consistently. C1 Univ Fribourg, Dept Phys, CH-1700 Fribourg, Switzerland. NIH, Natl Biotechnol Ctr, Bethesda, MD 20894 USA. RP Laureti, P (reprint author), Univ Fribourg, Dept Phys, CH-1700 Fribourg, Switzerland. NR 13 TC 49 Z9 51 U1 1 U2 8 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0295-5075 J9 EUROPHYS LETT JI Europhys. Lett. PD SEP PY 2006 VL 75 IS 6 BP 1006 EP 1012 DI 10.1209/epl/i2006-10204-8 PG 7 WC Physics, Multidisciplinary SC Physics GA 098AE UT WOS:000241491200025 ER PT J AU Athar, M Tang, XW Lee, JL Kopelovich, L Kim, AL AF Athar, Mohammad Tang, Xiuwei Lee, Juliette L. Kopelovich, Levy Kim, Arianna L. TI Hedgehog signalling in skin development and cancer SO EXPERIMENTAL DERMATOLOGY LA English DT Review DE BCC; cancer; development; skin; sonic hedgehog; stem cell ID BASAL-CELL CARCINOMA; HAIR FOLLICLE MORPHOGENESIS; SONIC-HEDGEHOG; ORNITHINE-DECARBOXYLASE; TRANSPLANT RECIPIENTS; CYCLE PROGRESSION; INDIAN HEDGEHOG; MOUSE SKIN; PATHWAY; CHEMOPREVENTION AB Basal cell carcinoma (BCC) is the most common human malignancy, affecting 750 000 Americans each year. The understanding of mutations that are known to activate hedgehog (Hh) signalling pathway genes, including PATCHED (PTCH), sonic hedgehog (Shh) and smoothened (Smo), has substantially expanded our current understanding of the genetic basis of BCC development. The Hh signalling pathway is one of the most fundamental signal transduction pathways in embryonic development. In skin, the Shh pathway is crucial for maintaining stem cell population, and for regulating hair follicle and sebaceous gland development. This pathway plays a minimal role in adult tissues, but is known to be activated in many neoplasms, including those arising in the skin. In this review, we attempt to summarize the results of published studies on some important aspects of the Shh pathway and its involvement in skin development and carcinogenesis. We also provide a description of various animal models that have been developed, based on our knowledge of the Shh pathway in human skin cancers. Additionally, we include a brief description of studies conducted in our laboratory and by others on the chemoprevention of BCCs. This review therefore provides a current understanding of the role of the Shh pathway in skin development and neoplasia. It also provides a basis for the molecular target-based chemoprevention and therapeutic management of skin cancer. C1 Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. Stanford Univ, Dept Dermatol, Stanford, CA 94305 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Athar, M (reprint author), Columbia Univ Coll Phys & Surg, Dept Dermatol, 630 W 168th St,VC15-204, New York, NY 10032 USA. EM ma493@columbia.edu FU NCI NIH HHS [N01-CN-15011-72, CA-10106-01, N01-CN-15109, N01-CN-35006-72, N01-CN-35105, N01-CN-43300, R01 CA-97249, R03 CA-101061, U19 CA 81888] NR 65 TC 105 Z9 106 U1 0 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD SEP PY 2006 VL 15 IS 9 BP 667 EP 677 DI 10.1111/j.0906-6705.2006.00473.x PG 11 WC Dermatology SC Dermatology GA 068JZ UT WOS:000239371200003 PM 16881963 ER PT J AU Karlsson, G Blank, U Moody, JL Ehinger, M Singbrant, S Deng, CX Karlsson, S AF Karlsson, G. Blank, U. Moody, J. L. Ehinger, M. Singbrant, S. Deng, C. X. Karlsson, S. TI A critical role for Smad4 in the self-renewal of hematopoietic stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Univ Lund Hosp, Stem Cell Ctr, S-22185 Lund, Sweden. NIDDK, NIH, Bethesda, MD USA. Dept Pathol, Helsingborgs Lasarett, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 27 BP 41 EP 41 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500028 ER PT J AU Chen, J Young, NS AF Chen, J. Young, N. S. TI Lymphocytes expansion, V-beta shifting, and regulatory T cell suppression in immune-mediated bone marrow failure SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 40T78 BP 45 EP 45 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500041 ER PT J AU Baerlocher, GM Alter, BP Calado, RT Chanock, SJ Yamaguchi, H Young, NS Goldman, F Klingelhutz, AJ Vulto, I Lansdorp, M AF Baerlocher, G. M. Alter, B. P. Calado, R. T. Chanock, S. J. Yamaguchi, H. Young, N. S. Goldman, F. Klingelhutz, A. J. Vulto, I. Lansdorp, M. TI Telomere length and stem cell maintenance SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 BCCRC, Terry Fox Lab, Vancouver, BC, Canada. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA USA. Univ Bern, Dept Hematol, Bern, Switzerland. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 61 BP 51 EP 51 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500062 ER PT J AU Gause, BL Cohen, CM Katz, LM Watson, TM Arikian, S Stergiou, AM AF Gause, B. L. Cohen, C. M. Katz, L. M. Watson, T. M. Arikian, S. Stergiou, A. M. TI Biovaxid vaccine therapy of follicular lymphoma in first remission: Long-term follow-up of a phase II trial and status of a controlled, randomized phase III trial SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 NCI, Bethesda, MD 20892 USA. Bioinvest Int, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 76T16 BP 54 EP 54 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500075 ER PT J AU Albanese, J Schreyer, SK Fostel, J Dainiak, N AF Albanese, J. Schreyer, S. K. Fostel, J. Dainiak, N. TI Examination of gene expression data using dimensional reduction methodology: A comparative study between principal component analysis and projection pursuit SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Yale New Haven Ctr Emergency Preparedness & Disas, New Haven, CT USA. Chem Comp Grp, Montreal, PQ, Canada. NIH, Bethesda, MD USA. Bridgeport Hosp, Bridgeport, CT USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 141T31 BP 70 EP 71 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500138 ER PT J AU Erie, EA Ellison, FM Young, NS Chen, J AF Erie, E. A. Ellison, F. M. Young, N. S. Chen, J. TI Stromal injury in mouse models of infusion-induced bone marrow failure and the role of regulatory T cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Society-for-Experimental-Hematology CY SEP 27-30, 2006 CL Minneapolis, MN SP Int Soc Expert Hemat C1 Natl Inst Hlth, Natl Heart Lung & Blood Inst, Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2006 VL 34 IS 9 SU 1 MA 161T77 BP 76 EP 76 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 085RG UT WOS:000240621500158 ER PT J AU Lepore, AC Walczak, P Rao, MS Fischer, I Bulte, JWM AF Lepore, A. C. Walczak, P. Rao, M. S. Fischer, I. Bulte, J. W. M. TI MR imaging of lineage-restricted neural precursors following transplantation into the adult spinal cord SO EXPERIMENTAL NEUROLOGY LA English DT Article DE neural progenitors; migration; magnetic resonance imaging; transplantation; superparamagnetic iron oxide ID MAGNETIC-RESONANCE TRACKING; NEUROEPITHELIAL STEM-CELLS; IN-VIVO TRACKING; RAT-BRAIN; PROGENITOR CELLS; IRON; CNS; DIFFERENTIATION; MIGRATION; NEURONS AB Neural precursor cell (NPC) transplantation is a promising strategy for treatment of CNS injuries and neurodegenerative disorders because of potential for cell replacement. An important element of future clinical applications is development of a non-invasive procedure to follow NPC fate. We show that neuronal-restricted precursors (NRPs) and glial-restricted precursors (GRPs), NPCs with lineage restrictions for neurons and glia, respectively, can be labeled in vitro with the superparamagnetic iron oxide contrast agent Feridex. Following engraftment into intact adult spinal cord, labeled cells robustly survived in white and gray matter and migrated selectively along white matter tracts up to 5 turn. Localization of cells was reliably established using ex vivo magnetic resonance imaging of spinal cords. Imaging coincided with histological detection of iron and the human alkaline phosphatase transgene in most grafting sites, including the stream of migrating cells. Following transplantation, magnetically labeled cells exhibited mature morphologies and differentiated into neurons, astrocytes, and oligodendrocytes, similar to grafts of unlabeled NRPs and GRPs. Interestingly, Feridex-labeled cells, but not unlabeled cells, induced influx of ED1-positive macrophages/microglia. Small numbers of these phagocytic cells took LIP iron from grafted cells, while the majority of Feridex label was found in transplanted cells. We conclude that Feridex labeling does not inhibit NPC differentiation and can be used to reliably localize NPCs by MRI following engraftment into adult CNS, with the possible exception of areas of rapidly proliferating cells. The present results are relevant for MR-guided clinical application of transplantation strategies in treatment of spinal cord injury and other CNS pathologies. (c) 2006 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Russel H Morgan Dept Radiol & Radiol Sci, Div MR Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Bulte, JWM (reprint author), Johns Hopkins Univ, Sch Med, Russel H Morgan Dept Radiol & Radiol Sci, Div MR Res, 217 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM jwmbulte@mri.jhu.edu RI Bulte, Jeff/A-3240-2008; Walczak, Piotr/B-8707-2008; Fischer, Itzhak/D-1080-2012; OI Bulte, Jeff/0000-0003-1202-1610; Fischer, Itzhak/0000-0003-3187-8740; Walczak, Piotr/0000-0002-3733-3322 FU NINDS NIH HHS [NS 024707, NS 037515, NS 045062] NR 44 TC 56 Z9 63 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2006 VL 201 IS 1 BP 49 EP 59 DI 10.1016/j.expneurol.2006.03.032 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 079CC UT WOS:000240152100006 PM 16764862 ER PT J AU Banerjee, HN Verma, M AF Banerjee, Hirendra Nath Verma, Mukesh TI Use of nanotechnology for the development of novel cancer biomarkers SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE microarray; nanomedicine; raman spectroscopy; surface enhanced laser desorption/ionization ID MOLECULAR DIAGNOSTICS; PROTEIN MICROARRAYS; CLASSIFICATION; SUBTYPE; CELLS AB Novel nanotechnologies can complement and augment existing genomic and proteomic techniques employed to analyze variations across different tumor types, thus offering the potential to distinguish between normal and malignant cells. Sensitive biosensors constructed out of nanoscale components (e.g., nanocantilevers, nanowires and nanochannels) can recognize genetic and molecular events and have reporting capabilities, thereby offering the potential to detect rare molecular signals associated with malignancy. Such signals may then be collected for analysis by nanoscale harvesters that selectively isolate cancer-related molecules from tissues. Another area with near-term potential for the early detection of cancer is the identification of mutations and genomic instability. C1 Univ N Carolina, Dept Biol Sci & Pharmaceut Sci, Div Math Sci Technol & Pharmaceut Sci, Elizabeth City State Univ, Elizabeth City, NC 27909 USA. NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Banerjee, HN (reprint author), Univ N Carolina, Dept Biol Sci & Pharmaceut Sci, Div Math Sci Technol & Pharmaceut Sci, Elizabeth City State Univ, Room 425,Jenkins Sci Bldg,1704 Weeksville Rd, Elizabeth City, NC 27909 USA. EM bhirendranath@mail.ecsu.edu NR 25 TC 7 Z9 8 U1 0 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD SEP PY 2006 VL 6 IS 5 BP 679 EP 683 DI 10.1586/14737159.6.5.679 PG 5 WC Pathology SC Pathology GA 093AA UT WOS:000241138300003 PM 17009903 ER PT J AU Bjork, K Saarikoski, ST Arlinde, C Kovanen, L Osei-Hyiaman, D Ubaldi, M Reimers, M Hyytia, P Heilig, M Sommer, WH AF Bjork, K. Saarikoski, S. T. Arlinde, C. Kovanen, L. Osei-Hyiaman, D. Ubaldi, M. Reimers, M. Hyytia, P. Heilig, M. Sommer, W. H. TI Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity SO FASEB JOURNAL LA English DT Article DE alcoholism; aging; animal model; microarray; haplotype ID ALCOHOL-NONPREFERRING RATS; ANTIOXIDANT SYSTEM; OXIDATIVE STRESS; MICROARRAY DATA; ANIMAL-MODELS; GENETIC MODEL; ANA RATS; DETOXICATION; CONSUMPTION; ASSOCIATION AB Identification of genes that are differentially expressed in rats bidirectionally selected for alcohol preference might reveal biological mechanisms underlying alcoholism or related phenotypes. Microarray analysis from medial prefrontal cortex (mPFC), a key brain region for drug reward, indicated increased expression of glutathione-S-transferases of the alpha (Gsta4) and mu (Gstm1-5) classes in ethanol-preferring AA rats compared with nonpreferring ANA rats. Real-time RT polymerase chain reaction (RT-PCR) analysis demonstrated similar to 2-fold higher Gsta4 transcript levels in several brain regions of ethanol-naive AA compared with ANA rats. Differences in mRNA levels were accompanied by differential levels of GSTA4 protein. We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3. Allele frequencies of var3 were markedly different between AA and ANA rats, 52% and 100%, respectively. Gsta4 expression was strongly correlated with the gene dose of var3, with similar to 60% of the variance in expression accounted for by genotype at this locus. The contribution of glutathione S-transferase expression to the ethanol-preferring phenotype is presently unclear. It could, however, underlie observed differences in life span between AA and ANA lines, prompting a utility of this animal model in aging research. - Bjork, K., Saarikoski, S. T., Arlinde, C., Kovanen, L., Osei-Hyiaman, D., Ubaldi, M., Reimers, M., Hyytia, P., Heilig, M. Sommer, W. H. Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity. C1 NIAAA, Lab Clin & Translat Studies, NCI, NIH, Bethesda, MD USA. NIAAA, Lab Physiol Studies, NCI, NIH, Bethesda, MD USA. NIAAA, Mol Pharmacol Lab, NCI, NIH, Bethesda, MD USA. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. Natl Publ Hlth Inst, Dept Mental Hlth & Alcohol Res, Helsinki, Finland. Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Italy. RP Sommer, WH (reprint author), NIAAA, Lab Clin & Translat Studies, NCI, NIH, 10 Center Dr,B 10,R 15330, Bethesda, MD USA. EM wolfgang.sommer@mail.nih.gov OI Kovanen, Leena/0000-0002-3552-124X; Ubaldi, Massimo/0000-0002-4089-2483; Hyytia, Petri/0000-0002-0284-1298 FU Intramural NIH HHS NR 58 TC 23 Z9 23 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2006 VL 20 IS 11 BP 1826 EP 1835 DI 10.1096/fj.06-5896com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RZ UT WOS:000240267000010 PM 16940154 ER PT J AU Movafagh, S Hobson, JP Spiegel, S Kleinman, HK Zukowska, Z AF Movafagh, Sharareh Hobson, John P. Spiegel, Sarah Kleinman, Hynda K. Zukowska, Zofia TI Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors SO FASEB JOURNAL LA English DT Article DE bimodal dose-response curve; chemotaxis; mitogenesis; oligomerization; GPCRs ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; THERAPEUTIC IMPLICATIONS; ISCHEMIC ANGIOGENESIS; MOLECULAR-MECHANISMS; NPY; SUBTYPES; HORMONE; NEURONS; NEOVASCULARIZATION AB sPreviously we discovered that NPY induces ischemic angiogenesis by activating Y2 and Y5 receptors. The receptors that mediate specific steps of the complex process of angiogenesis are unknown. Here, we studied in vitro NPY receptors subtypes involved in migration, proliferation, and differentiation of human endothelial cells. In cells that expressed Y1, Y2, and Y5 receptors, NPY bimodally stimulated migration and proliferation with a 2-fold increase at 10(-12) M and 10(-8) M (high- and low-affinity peaks, respectively). Preincubation of cells with NPY up-regulated the Y5 receptor and markedly enhanced endothelial cell migration and proliferation. NPY-induced endothelial cell migration was mimicked by agonists and fully blocked by antagonists for any specific NPY receptors (Y1, Y2, or Y5), while proliferation was blocked by any two antagonists (Y1 + Y2, Y1 + Y5, or Y2 + Y5), and capillary tube formation on Matrigel was blocked by all three (Y1 + Y2 + Y5). Thus, NPY-induced angiogenesis requires participation of Y1, Y2, and Y5 receptor subtypes, with the Y5 receptor acting as an enhancer. We propose that these receptors form heteromeric complexes, and the Y1/ Y2/ Y5 receptor oligomer may be the uncloned Y3 receptor. C1 Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Zukowska, Z (reprint author), Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20057 USA. EM zzukow01@georgetown.edu FU NHLBI NIH HHS [HL67357, HL0553] NR 55 TC 70 Z9 77 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2006 VL 20 IS 11 BP 1924 EP + DI 10.1096/fj.05-4770fje PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RZ UT WOS:000240267000032 PM 16891622 ER PT J AU Rouzaud, F Costin, GE Yamaguchi, Y Valencia, JC Berens, WF Chen, KG Hoashi, T Bohm, M Abdel-Malek, ZA Hearing, VJ AF Rouzaud, Francois Costin, Gertrude-E. Yamaguchi, Yuji Valencia, Julio C. Berens, Werner F. Chen, Kevin G. Hoashi, Toshihiko Boehm, Markus Abdel-Malek, Zalfa A. Hearing, Vincent J. TI Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms SO FASEB JOURNAL LA English DT Article DE splice variant; melanocyte; UVR ID STIMULATING-HORMONE-RECEPTOR; PROTEIN-COUPLED RECEPTORS; ULTRAVIOLET-RADIATION; HUMAN MELANOCYTES; MSH RECEPTOR; RED HAIR; AFRICAN-AMERICANS; CYTOPLASMIC TAIL; COAT COLOR; GENE AB Melanin synthesized by epidermal melanocytes protects the skin against UVR-induced DNA damage and skin cancer. Exposure to UVR increases the synthesis of the photoprotective eumelanin on activation of MC1R, a melanoma susceptibility gene. We studied the expression of MC1R under UVR and alpha-MSH stimulation in skin of different ethnic origins and in melanocytes of various pigmentary levels. This study identifies and characterizes a novel MC1R isoform (MC1R350) generated by alternative splicing of the classically known MC1R (MC1R317). We demonstrate that the melanin content of melanocytes shows a significant positive correlation with MC1R317 levels but correlates inversely with the amount of MC1R350, suggesting that this latter isoform could act as a negative regulator of melanin synthesis. We confirmed that hypothesis by showing that while MC1R317 signaling significantly increases the expression of MITF and tyrosinase, two key factors in the melanin synthesis pathway, MC1R350 dramatically hampers their expression. In the skin, we show that UVR does not increase MC1R350 expression but does significantly increase MC1R317. Taken together, our results strongly suggest that MC1R350 acts as a negative regulator of skin pigmentation and demonstrate for the first time that MC1R isoform-specific expression is closely related to skin pigmentation and photoprotection. C1 Univ Florida, Dept Med Chem, Gainesville, FL 32610 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Munster, Dept Dermatol, D-4400 Munster, Germany. Univ Munster, Ludwig Boltzmann Inst Cell Biol & Immunobiol Skin, D-4400 Munster, Germany. Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH USA. RP Rouzaud, F (reprint author), Univ Florida, Dept Med Chem, Rm P5-26,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM frouzaud@ufl.edu RI Yamaguchi, Yuji/B-9312-2008; Chen, Kevin/D-6769-2011 OI Chen, Kevin/0000-0003-2983-6330 FU Intramural NIH HHS [Z99 NS999999]; NIEHS NIH HHS [R01 ES009110] NR 58 TC 25 Z9 28 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2006 VL 20 IS 11 BP 1927 EP + DI 10.1096/fj.06.5922fje PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 080RZ UT WOS:000240267000033 PM 16877522 ER PT J AU Parker, JD Leondires, M Sinaii, N Premkumar, A Nieman, LK Stratton, P AF Parker, Jason D. Leondires, Mark Sinaii, Ninet Premkumar, Ahalya Nieman, Lynnette K. Stratton, Pamela TI Persistence of dysmenorrhea and nonmenstrual pain after optimal endometriosis surgery may indicate adenomyosis SO FERTILITY AND STERILITY LA English DT Article DE adenomyosis; endometriosis; chronic pelvic pain; magnetic resonance imaging; junctional zone thickness; visual analog scale ID UTERINE JUNCTIONAL ZONE; CHRONIC PELVIC PAIN; TRANSVAGINAL SONOGRAPHY; PRIMARY-CARE; UTERUS; PREVALENCE; DIAGNOSIS; US; DIFFERENTIATION; ULTRASONOGRAPHY AB Objective: To evaluate whether persistence of pelvic pain after excision of endometriosis was associated with adenomyosis as defined by a thickened uterine junctional zone (JZ) on magnetic resonance (MR) imaging. Design: Prospective clinical trial. Setting: Government research hospital. Patients(s): Fifty-three women with chronic pelvic pain. Intervention(s): Preoperative MR imaging to measure uterine JZ thickness, surgical excision, and pathological diagnosis of endometriosis. Those with biopsy-proven endometriosis were randomised to raloxifene or placebo. Visual analog scale (VAS) was used to rate dysmenorrhea and nonmenstrual pain severity before and 3 months later. Main Outcome Measure(s): Comparison of JZ thickness and pain severity before and 3 months after surgery in women with endometriosis controlling for medical treatment. Results(s): Forty of the 53 patients had biopsy proven endometriosis, and 6 of these 40 women with endometriosis had a thickened JZ. Overall, dysmenorrhea at 3 months was positively correlated with preoperative JZ thickness (r=0.47, P=.01). Dysmenorrhea pain severity showed no significant decrease in those patients whose JZ measured >= 11 mm compared with those with JZ < 8mm (P <.0001; VAS decreased 4.3 +/- 0.6), or >= 8 and < 11 mm (P <.02 VAS decreased 4.8 +/- 1.3). Nonmenstrual pain severity was correlated with JZ thickness (r=0.51, P=.004) at 3 months with a significant decrease in nonmenstrual pain only in woman with a JZ < 8 mm (VAS decreased 4.0 +/- 0.7, P <.0001). The associated between dysmenorrhea and nonmenstual pain reduction and thinner JZ remained after controlling for medical treatment. Conclusion(s): Following surgical excision of endometriosis, chronic pelvic pain was significantly more likely to persist with JZ thickness > 11mm on preoperative MR imaging. This suggests that mymometrial JZ abnormalities or adenomyosis may contribute to chronic pelvic pain in women with endometriosis. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Walter Reed Army Med Ctr, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Reprod Med Assoc Connecticut, Norwalk, CT USA. NIH, Ctr Clin, Dept Radiol, Bethpage, MD USA. RP Stratton, P (reprint author), NICHD, RBMB, NIH, 10 Ctr Dr,Bldg 10 CRC,1 E-3140, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural NIH HHS NR 36 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 IS 3 BP 711 EP 715 DI 10.1016/j.fertnstert.2006.01.030 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091AN UT WOS:000240998000037 PM 16782099 ER PT J AU Parker, J Sinaii, N Segars, J Godoy, H Winkel, C Stratton, P AF Parker, Jason Sinaii, Ninet Segars, James Godoy, Heidi Winkel, Craig Stratton, Pamela TI Dissecting and temporarily resuspending the adherent ovary - Reply SO FERTILITY AND STERILITY LA English DT Letter ID LAPAROSCOPIC EXCISION; ENDOMETRIOSIS C1 Natl Naval Med Ctr, Walter Reed Army Med Ctr, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Dept Obstet & Gynecol, Bethesda, MD USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Parker, J (reprint author), Natl Naval Med Ctr, Walter Reed Army Med Ctr, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 IS 3 BP 772 EP 773 DI 10.1016/j.fertnstert.2006.07.1465 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091AN UT WOS:000240998000061 ER PT J AU Alvero, R Segars, J Catherino, W Armstrong, A AF Alvero, R. Segars, J. Catherino, W. Armstrong, A. TI Endometrial patterns in African American and Caucasian women in the presence and absence of fibroids. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Univ Colorado Denver & Hlth Sci Ctr, Reprod Biol & Med Branch, Aurora, CO USA. NICHD, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S50 EP S51 DI 10.1016/j.fertnstert.2006.07.138 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500118 ER PT J AU Blocker, W Nansel, T Potlog-Nahari, C Armstrong, A Nieman, L AF Blocker, W. Nansel, T. Potlog-Nahari, C. Armstrong, A. Nieman, L. TI Correlation of subjective symptoms in women with symptomatic leiomyoma with hematocrit and uterine size. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Reproduct Biol & Med Branch, Bethesda, MD USA. NICHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S91 EP S92 DI 10.1016/j.fertnstert.2006.07.245 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500214 ER PT J AU Browne, HN Robinson, N Sherry, R Stratton, P AF Browne, H. N. Robinson, N. Sherry, R. Stratton, P. TI Obturator hernia presenting as a cause of recurrent pain in a patient with previously diagnosed endometriosis. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD USA. NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Ob Gyn, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S303 EP S303 DI 10.1016/j.fertnstert.2006.07.812 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501219 ER PT J AU Catherino, WH Malik, M Payson, M Segars, JH Britten-Webb, J AF Catherino, W. H. Malik, M. Payson, M. Segars, J. H. Britten-Webb, J. TI Human leiomyomas minimize retinoic acid exposure by altering transport and metabolism gene expression. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S41 EP S41 DI 10.1016/j.fertnstert.2006.07.111 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500096 ER PT J AU Elizondo, J Raygada, MJ Mcconkie-Rosell, A Vanderhoof, VH Calis, KA Nelson, LM AF Elizondo, J. Raygada, M. J. Mcconkie-Rosell, A. Vanderhoof, V. H. Calis, K. A. Nelson, L. M. TI Genetic testing for the fMR1 premutation in young women with spontaneous premature ovarian failure. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, Bethesda, MD USA. NIH, NICHHD, Lab Clin Genom, Bethesda, MD USA. Duke Univ, Med Ctr, Dept Pediat & Med Genet, Durham, NC USA. NIH, Mark O Hatfield Clin Res Ctr, Dept Pharm, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S47 EP S47 DI 10.1016/j.fertnstert.2006.07.128 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500110 ER PT J AU Feinberg, EC Gustofson, RL Levens, ED Larsen, FW Decherney, AH AF Feinberg, E. C. Gustofson, R. L. Levens, E. D. Larsen, F. W. Decherney, A. H. TI Pre-cycle screening with saline sonography minimizes cycle cancellation due to endometrial polyps. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S151 EP S151 DI 10.1016/j.fertnstert.2006.07.404 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500356 ER PT J AU Feinberg, EC Larsen, FW Wah, RM Alvero, RJ Armstrong, AY AF Feinberg, E. C. Larsen, F. W. Wah, R. M. Alvero, R. J. Armstrong, A. Y. TI Economics cannot always explain minority underutilization of assisted reproductive technologies. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Walter Reed Army Med Ctr, ART Program, Washington, DC USA. NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Div Reprod Endocrinol & Infertil, Washington, DC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S35 EP S35 DI 10.1016/j.fertnstert.2006.07.097 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500083 ER PT J AU Hammond, CT Aziz, N Syrjala, K AF Hammond, C. T. Aziz, N. Syrjala, K. TI Correlates of conception and fertility related concern in 10 year adult henatopoetic stem cell transplant recipients. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Off Canc Survivorship, Bethesda, MD USA. Natl Canc Inst, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S192 EP S192 DI 10.1016/j.fertnstert.2006.07.510 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500459 ER PT J AU Leppert, PC Abu-Asab, M Rogers, RE Catherino, WH Tsokos, M Segars, JH AF Leppert, P. C. Abu-Asab, M. Rogers, R. E. Catherino, W. H. Tsokos, M. Segars, J. H., Jr. TI The ultrastructural organization of myofibroblasts within uterine fibroids suggests alteration of tensional homeostasis. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Duke Univ, Durham, NC USA. NIH, NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. USUHS, Dept Obstet & Gynecol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S344 EP S344 DI 10.1016/j.fertnstert.2006.07.934 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501328 ER PT J AU Levens, ED Gustofson, RL Feinberg, EC Larsen, FW AF Levens, E. D. Gustofson, R. L. Feinberg, E. C. Larsen, F. W. TI The ultrasonographic endometrial thickness and pattern of patients with fibroids is not significantly different than controls at the time of hCG administration in art cycles. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. Walter Reed Army Med Ctr, ART Program, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S344 EP S345 DI 10.1016/j.fertnstert.2006.07.936 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501330 ER PT J AU Levens, ED Gustofson, RL Hennessy, S James, AN Wiemer, KE Larsen, FW AF Levens, E. D. Gustofson, R. L. Hennessy, S. James, A. N. Wiemer, K. E. Larsen, F. W. TI Implantation rate and pregnancy outcomes are significantly improved in cryopreserved blastocyst transfers when frozen at day 5 compared to day 6. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, NICHD, Walter Reed Army Med Ctr, Reprod Biol & Med Branch ART Program, Bethesda, MD USA. ART Inst Washington Inc, Washington, DC USA. Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S256 EP S257 DI 10.1016/j.fertnstert.2006.07.682 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501096 ER PT J AU Mahoney, SF Zarate, C AF Mahoney, S. F. Zarate, C. TI A case of persistent sexual arousal syndrome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S494 EP S494 DI 10.1016/j.fertnstert.2006.07.1367 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038502234 ER PT J AU Payson, M Malik, M Segars, J Catherino, W AF Payson, M. Malik, M. Segars, J. Catherino, W. TI Activating Transcription Factor 3: A link between stress, apoptosis, and leiomyoma development. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, NICHHD, Reprod Biol & Med Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S41 EP S41 DI 10.1016/j.fertnstert.2006.07.112 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500097 ER PT J AU Robinson, N Feinberg, EC Gustofson, RL Neithardt, AB McKeeby, JL Segars, J AF Robinson, N. Feinberg, E. C. Gustofson, R. L. Neithardt, A. B. McKeeby, J. L. Segars, J., Jr. TI The 'afterload' method of embryo transfer reduces the incidence of retained embryos following embryo transfer and may be superior to the direct insertion method of embryo transfer. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, ART Program, Washington, DC USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S253 EP S254 DI 10.1016/j.fertnstert.2006.07.673 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501089 ER PT J AU Rogers, RE Williams, S Chen, FH Leppert, PC Catherino, WH Segars, JH AF Rogers, R. E. Williams, S. Chen, F. H. Leppert, P. C. Catherino, W. H. Segars, J. H., Jr. TI Is mechanical tension-homeostasis altered in uterine leiomyoma cells? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NIH, NIAMS, Bethesda, MD 20892 USA. Duke Univ, Durham, NC USA. USUHS, Dept Obstet & Gynecol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S342 EP S343 DI 10.1016/j.fertnstert.2006.07.931 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501325 ER PT J AU Sinaii, N Cleary, SD Younes, N Knoff, D Ballweg, ML Stratton, P AF Sinaii, N. Cleary, S. D. Younes, N. Knoff, D. Ballweg, M. L. Stratton, P. TI Treatment utilization for endometriosis symptoms: A cross-sectional survey study of lifetime experience. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Natl Inst Hlth, Bethesda, MD USA. George Washington Univ, Washington, DC USA. Endometriosis Assoc, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S264 EP S265 DI 10.1016/j.fertnstert.2006.07.704 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038501117 ER PT J AU Sproul, K Deugarte, CM Decherney, A AF Sproul, K. Deugarte, C. M. Decherney, A. TI A comparison of pre-pregnancy to postpartum sexual function. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 Univ Calif Los Angeles, Los Angeles, CA USA. Henry Ford Hosp, Detroit, MI 48202 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S31 EP S31 DI 10.1016/j.fertnstert.2006.07.085 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500073 ER PT J AU Stegmann, BJ Henne, MB Neithardt, AB Catherino, WH Kao, TC Segars, JH AF Stegmann, B. J. Henne, M. B. Neithardt, A. B. Catherino, W. H. Kao, T. C. Segars, J. H. TI Cost analysis of a successful art cycle in women with an elevated day 3 FSH. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, ART Program, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S35 EP S36 DI 10.1016/j.fertnstert.2006.07.098 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500084 ER PT J AU Ventura, JL Davis, MC Calis, KA Koziol, DE Covington, SN Nelson, LM AF Ventura, J. L. Davis, M. C. Calis, K. A. Koziol, D. E. Covington, S. N. Nelson, L. M. TI Symptoms of depression and their impact on daily functioning in women with spontaneous premature ovarian failure. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NICHD, Sect Womens Hlth Res DEB, NIH, Bethesda, MD USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. NIH, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA. NIH, Biostat Serv, Clin Res Ctr, Bethesda, MD 20892 USA. NIH, Clin Epidemiol Serv, Clin Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S54 EP S54 DI 10.1016/j.fertnstert.2006.07.149 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500128 ER PT J AU Wittenberger, MD Larsen, FW Segars, JH AF Wittenberger, M. D. Larsen, F. W. Segars, J. H. TI Response to superovulation does not predict pre-term delivery in pregnancies resulting from ART SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 21-25, 2006 CL New Orleans, LA SP Amer Soc Reprod Med C1 NIH, NICHD, Reprod Biol & Med Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2006 VL 86 SU 2 BP S112 EP S113 DI 10.1016/j.fertnstert.2006.07.301 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 091OP UT WOS:000241038500263 ER PT J AU Rubin, JS Barshishat-Kupper, M Feroze-Merzoug, F Xi, ZF AF Rubin, JS Barshishat-Kupper, M Feroze-Merzoug, F Xi, ZF TI Secreted WNT antagonists as tumor suppressors: pro and con SO FRONTIERS IN BIOSCIENCE LA English DT Review DE sFRP; Dickkopf; WIF-1; Wnt; tumor suppressor; review ID FRIZZLED-RELATED PROTEIN; BETA-CATENIN PATHWAY; INHIBITORY FACTOR-I; CHROMOSOME ARM 8P; PROMOTER-HYPERMETHYLATION; WNT/BETA-CATENIN; DICKKOPF PROTEINS; SIGNALING PATHWAY; DOWN-REGULATION; GENE FAMILY AB Dysregulation of Wnt signaling is common in a variety of human malignancies. Activation of the canonical Wnt or beta-catenin pathway has been especially well documented in cancer, although other non-canonical Wnt signaling pathways also have been implicated in neoplasia. In most instances, constitutive signaling through the beta-catenin pathway involves activation of effector molecules or loss of tumor suppressor function downstream of Wnt binding to its cell surface receptors. Nonetheless, in recent years increasing evidence suggests that secreted Wnt antagonists act as tumor suppressors, with their expression often silenced by promoter hypermethylation. This implies that maximal constitutive signaling in cancer requires unimpaired Wnt stimulation at the cell surface as well as enhanced signal propagation within the cell. However, an understanding of the role secreted Wnt antagonists may play in cancer is complicated by the multiplicity of these proteins, their potential Wnt-independent activities and observations indicating that sometimes they may promote tumor growth. Just as the particular function of Wnt signaling in development and homeostasis varies with the setting, the impact of secreted Wnt antagonists on neoplasia depends on the molecular, cellular and tissue context. C1 Natl Canc Inst, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Rubin, JS (reprint author), Natl Canc Inst, Cellular & Mol Biol Lab, Bldg 37,Room 2042,37 Convent Dr, Bethesda, MD 20892 USA. EM rubinj@mail.nih.gov FU Intramural NIH HHS NR 113 TC 56 Z9 60 U1 0 U2 5 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2006 VL 11 BP 2093 EP 2105 DI 10.2741/1952 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 040ML UT WOS:000237382800011 PM 16720296 ER PT J AU Zheng, ZM Baker, CC AF Zheng, ZM Baker, CC TI Papillomavirus genome structure, expression, and post-transcriptional regulation SO FRONTIERS IN BIOSCIENCE LA English DT Review DE papillomaviruses; gene expression; RNA splicing; RNA polyadenylation; posttranscriptional regulation; review ID EXONIC SPLICING SUPPRESSOR; PRE-MESSENGER-RNA; HUMAN-IMMUNODEFICIENCY-VIRUS; CAPSID GENE-EXPRESSION; CERVICAL-CANCER CELLS; 3 UNTRANSLATED REGION; TYPE-16 E2 PROTEIN; OPEN READING FRAME; VIRAL LIFE-CYCLE; L2 CODING REGION AB Papillomaviruses are a group of small non-enveloped DNA tumor viruses whose infection usually causes benign epithelial lesions ( warts). Certain types of HPVs, such as HPV- 16, HPV- 18, and HPV- 31, have been recognized as causative agents of cervical cancer and anal cancer and their infections, which arise via sexual transmission, are associated with more than 95% of cervical cancer. Papillomaviruses infect keratinocytes in the basal layer of stratified squamous epithelia and replicate in the nucleus of infected keratinocytes in a differentiation-dependent manner. Viral gene expression in infected cells depends on cell differentiation and is tightly regulated at the transcriptional and post- transcriptional levels. A noteworthy feature of all papillomavirus transcripts is that they are transcribed as a bicistronic or polycistronic form containing two or more ORFs and are polyadenylated at either an early or late poly( A) site. In the past ten years, remarkable progress has been made in understanding how this complex viral gene expression is regulated at the level of transcription ( such as via DNA methylation) and particularly post- transcription ( including RNA splicing, polyadenylation, and translation). Current knowledge of papillomavirus mRNA structure and RNA processing has provided some clues on how to control viral oncogene expression. However, we still have little knowledge about which mRNAs are used to translate each viral protein. Continuing research on post- transcriptional regulation of papillomavirus infection will remain as a future focus to provide more insights into papillomavirus-host interactions, the virus life- cycle, and viral oncogenesis. C1 NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), 10 Ctr Dr Rm 10S255, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 SC010357-06] NR 153 TC 160 Z9 179 U1 4 U2 34 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2006 VL 11 BP 2286 EP 2302 DI 10.2741/1971 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 040ML UT WOS:000237382800030 PM 16720315 ER PT J AU Lee, JS Kim, IH Kim, SY AF Lee, JS Kim, IH Kim, SY TI Changes in gene expression with increased transglutaminase 2 in a SH-SY5Y cell line SO FRONTIERS IN BIOSCIENCE LA English DT Article DE inflammation; SH-SY5Y; neuroblastoma; transglutaminase 2; NF kappa B; microarray ID NF-KAPPA-B; VASOACTIVE-INTESTINAL-PEPTIDE; INCLUSION-BODY MYOSITIS; EPIDERMAL-GROWTH-FACTOR; TISSUE TRANSGLUTAMINASE; CROSS-LINKING; NITRIC-OXIDE; HUNTINGTON-DISEASE; BV-2 MICROGLIA; ACTIVATION AB Previously we showed that the overexpression of transglutaminase 2 (TGase 2) resulted in activation of NF-kappa B through polymerization of I-kappa alpha. To explore the pathway of TGase 2-mediated NF-kappa B activation, a transcriptomic microarray analysis was performed. In a SH-SY5Y cell line transfected with TGase 2, 24 genes were up-regulated at least 1.6-fold and 26 genes were downregulated, as compared to the wild-type cell line. Detailed analysis resulted in the identification of target genes involved in regulating inflammation, including tribbles homolog 3, peroxiredoxin 4, neuropeptide Y, galanin, and vasoactive intestinal peptide. Our data demonstrate that the increase in TGase 2 in the neuroblastoma causes functional changes in transcriptional regulation, especially in genes associated with inflammation. These changes in gene expression caused by increases in TGase 2 activity may contribute to the pathophysiologic processes of inflammatory diseases. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Inst Res, Goyang, Kyonggido, South Korea. RP Kim, SY (reprint author), 809 Madudong,Ilsandonggu, Goyang 410351, Kyonggido, South Korea. EM kimsooyoul@gmail.com NR 44 TC 5 Z9 5 U1 2 U2 4 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP 1 PY 2006 VL 11 BP 2774 EP 2781 DI 10.2741/2007 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 040ML UT WOS:000237382800066 PM 16720350 ER PT J AU Mannon, PJ Fuss, IJ Dill, S Friend, J Groden, C Hornung, R Yang, ZQ Yi, CL Quezado, M Brown, M Strober, W AF Mannon, Peter J. Fuss, Ivan J. Dill, Susie Friend, Julia Groden, Catherine Hornung, Ron Yang, Zhiqiong Yi, Chuli Quezado, Martha Brown, Margaret Strober, Warren TI Excess IL-12 but not IL-23 accompanies the inflammatory bowel disease associated with common variable immunodeficiency SO GASTROENTEROLOGY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; ACTIVE CROHNS-DISEASE; T-CELLS; GRANULOMATOUS-DISEASE; DENDRITIC CELLS; DEFICIENCY; ANTIBODY; HYPOGAMMAGLOBULINEMIA; ACTIVATION; DEFECTS AB Background & Aims: Common variable immunodeficiency (CVID) patients can develop an idiopathic inflammatory bowel disease resulting in chronic diarrhea and life-threatening malabsorption. This study was designed to assess the status of the gastrointestinal tract and to define the mucosal immune abnormalities in patients with and without symptomatic gut inflammatory disease. Methods: CVID patients underwent tests of gut absorption, peripheral blood mononuclear cell phenotyping, and upper and lower endoscopy for histology and lamina propria mononuclear cell (LPMC) cytokine production. Results: CVID patients with gastrointestinal symptoms differed from asymptomatic CVID patients by having significantly longer duration of disease and lower body mass index, D-xylose absorption, serum albumin, CD4/CD45RA cells, CD3/CD25 cells, and natural killer cells. Symptomatic CVID patients showed diffuse histologic inflammatory changes in the duodenal and colonic mucosa including villus blunting, increased lamina propria and intraepithelial lymphocytes, and epithelial apoptosis, less frequently seen in asymptomatic patients. LPMCs from symptomatic CVID patients produced significantly higher T-helper (Th) 1 cytokines, interleukin-12, and interferon-gamma. Compared with the Th1 cytokines produced by LPMCs from Crohn's disease, CVID patients did not produce excess amounts of interleukin-23, interleukin-17, or tumor necrosis factor-alpha. Conclusions: The idiopathic inflammatory bowel disease associated with gastrointestinal symptoms in CVID is a unique combination of diverse histologic findings accompanied by excessive Th1 cytokine production, distinct from that in Crohn's disease. These data show that human gut mucosal inflammatory disease can occur with excess interleukin-12 and interferon-gamma production alone and provide a rationale for developing targeted therapies for this complication of CVID. C1 NIA, Mucosal Immunity Sect, Host Def Lab, Clin Invest Lab,NIH,NIAID, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI Frederick, Clin Serv Program, Frederick, MD USA. NCI, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Mannon, PJ (reprint author), NIA, Mucosal Immunity Sect, Host Def Lab, Clin Invest Lab,NIH,NIAID, Bldg 10-CRC,Room 6-3742,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pmannon@niaid.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 56 TC 43 Z9 43 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2006 VL 131 IS 3 BP 748 EP 756 DI 10.1053/j.gastro.2006.06.022 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 084VF UT WOS:000240561800013 PM 16952544 ER PT J AU Fried, MW Kroner, BL Preiss, LR Wilhelmsen, K Goedert, JJ AF Fried, Michael W. Kroner, Barbara L. Preiss, Liliana R. Wilhelmsen, Kirk Goedert, James J. CA Multicenter Hemophilia Cohort TI Hemophilic siblings with chronic hepatitis C: Familial aggregation of spontaneous and treatment-related viral clearance SO GASTROENTEROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOGENEOUS PATIENT POPULATION; LIVER FIBROSIS PROGRESSION; NATURAL-HISTORY; UNITED-STATES; CLINICAL-OUTCOMES; GENE-EXPRESSION; HCV INFECTION; POLYMORPHISMS; DISEASE AB Background & Aims: Hemophilic siblings provide a unique population to explore the natural history of chronic hepatitis C. Methods: From 3993 hemophilic patients with hepatitis C, 257 sibling pairs, of which both members had evidence of hepatitis C infection, were studied to evaluate the genetic contribution to spontaneous and treatment-induced clearance of hepatitis C infection and progression of liver disease. Familial aggregation was assessed by comparing observed probabilities of concordance for these disease characteristics within sibling pairs to those expected for randomly paired hemophilic subjects. Additional measures of familial aggregation, heritability, and sibling relative risk were also calculated. Results: Among human immunodeficiency virus-negative subjects, concordance for spontaneous viral clearance was 2-fold higher in siblings compared with randomly paired subjects (8.8% vs 4.3%, respectively, P = .04). Similarly, the concordance rate for treatment-related viral clearance was over twice that among sibling pairs than among randomly paired hemophiliacs (31.3% vs 13.3%, respectively, P = ns). Heritability estimates for spontaneous and treatment-induced viral clearance were 0.24 +/- 0.14 (P = .04) and 0.43 +/- 0.42 (P = .10), respectively. The sibling relative risks for these respective characteristics were 1.6 and 1.7. Concordance for advanced liver disease was higher among siblings but did not reach statistical significance (4.0% vs 2.3%, respectively, P = ns). The heritability estimate was 0.29 +/- 0.13 (P = .02). Conclusions: Concordance rates and heritability estimates for spontaneous and treatment-related viral clearance indicate that genetic factors have a modest influence on the outcome of hepatitis C, although shared environmental factors cannot be excluded. Investigations to map candidate disease-susceptibility genes associated with these characteristics must be approached with caution. C1 Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA. Res Triangle Inst, Rockville, MD USA. Univ N Carolina, Dept Human Genet & Neurol, Chapel Hill, NC 27599 USA. Natl Canc Inst, Viral Epidemiol Branch, Rockville, MD USA. RP Fried, MW (reprint author), Univ N Carolina, Div Gastroenterol & Hepatol, CB 7584,Room 8015,Burnett Womck Bldg, Chapel Hill, NC 27599 USA. EM mfried@med.unc.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CP-01004]; NHLBI NIH HHS [R01 HL064817-02S1, R01 HL064817-01, R01 HL064817-03, R01 HL 64817-01, R01 HL064817, R01 HL064817-04, R01 HL064817-02]; NIDDK NIH HHS [K24 DK06614] NR 56 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2006 VL 131 IS 3 BP 757 EP 764 DI 10.1053/j.gastro.2006.07.001 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 084VF UT WOS:000240561800014 PM 16952545 ER PT J AU Young, MR Colburn, NH AF Young, Matthew R. Colburn, Nancy H. TI Fra-1 a target for cancer prevention or intervention SO GENE LA English DT Review DE AP-1; fosl1; TAM67; tumor promotion; invasion ID FOS-RELATED ANTIGEN-1; SQUAMOUS-CELL CARCINOMA; NEGATIVE C-JUN; GENE-EXPRESSION PROFILES; PROSTATE-CANCER; BETA-CATENIN; CYCLIN D1; TRANSCRIPTION FACTORS; INDUCED TRANSFORMATION; ACTIVATOR PROTEIN-1 AB The transcription factor activator protein-1 (AP-1) has been implicated as a driver of carcinogenesis since its original characterization. Oncogenic transcription factors like AP-1 are becoming new targets for cancer intervention. Inhibitors of AP-1 have been shown to block tumor promotion, transformation, progression and invasion. The Fos related antigen-1 (Fra-1) is activated in multiple cancers and gene ablation can suppress the invasive phenotypes of many tumor cell lines. This review focuses on the regulation of fosII expression, stabilization and activation of the Fra-1 polypeptide and on Fra-1-mediated tumorigenesis. Published by Elsevier B.V. C1 NCI Frederick, Lab Canc Prevent, Frederick, MD 21702 USA. RP Young, MR (reprint author), NCI Frederick, Lab Canc Prevent, Frederick, MD 21702 USA. EM youngm@ncifcrf.gov FU Intramural NIH HHS NR 107 TC 70 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 1 PY 2006 VL 379 BP 1 EP 11 DI 10.1016/j.gene.2006.05.001 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 086TI UT WOS:000240695500001 PM 16784822 ER PT J AU Datta, S Costantino, N Court, DL AF Datta, Simanti Costantino, Nina Court, Donald L. TI A set of recombineering plasmids for gram-negative bacteria SO GENE LA English DT Article DE recombination; bacteriophage lambda; gap-repair; functional genomics; gene knockouts; BAC engineering ID HOST-RANGE PLASMID; ESCHERICHIA-COLI; PHAGE-LAMBDA; HOMOLOGOUS RECOMBINATION; GENETIC-CHARACTERIZATION; BETA-PROTEIN; DNA; OLIGONUCLEOTIDES; CHROMOSOME; INTERMEDIATE AB We have constructed a set of plasmids that can be used to express recombineering functions in some gram-negative bacteria, thereby facilitating in vivo genetic manipulations. These plasmids include an origin of replication and a segment of the bacteriophage lambda genome comprising the red genes (exo, bet and gam) under their native control. These constructs do not require the anti-termination event normally required for Red expression, making their application more likely in divergent species. Some of the plasmids have temperature-sensitive replicons to simplify curing. In creating these vectors we developed two useful recombineering applications. Any gene linked to a drug marker can be retrieved by gap-repair using only a plasmid origin and target homologies. A plasmid origin of replication can be changed to a different origin by targeted replacement, to potentially alter its copy number and host range. Both these techniques will prove useful for manipulation of plasmids in vivo. Most of the Red plasmid constructs catalyzed efficient recombination in E. coli with a low level of uninduced background recombination. These Red plasmids have been successfully tested in Salmonella, and we anticipate that that they will provide efficient recombination in other related gram-negative bacteria. Published by Elsevier B.V. C1 NCI Frederick, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Court, DL (reprint author), NCI Frederick, Gene Regulat & Chromosome Biol Lab, Bldg 539,Room 243,POB B, Frederick, MD 21702 USA. EM court@ncifcrf.gov FU Intramural NIH HHS NR 31 TC 149 Z9 157 U1 4 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 1 PY 2006 VL 379 BP 109 EP 115 DI 10.1016/j.gene.2006.04.018 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 086TI UT WOS:000240695500012 PM 16750601 ER PT J AU Hippe, A Bylaite, M Chen, M von Mikecz, A Wolf, R Ruzicka, T Walz, M AF Hippe, Andreas Bylaite, Matilda Chen, Min von Mikecz, Anna Wolf, Ronald Ruzicka, Thomas Walz, Markus TI Expression and tissue distribution of mouse Hax1 SO GENE LA English DT Article DE gene expression; immunohistochemistry; apoptosis; cell motility ID POLYCYSTIC KIDNEY-DISEASE; MEDIATED ACTIN POLYMERIZATION; CELL MOTILITY; TYROSINE KINASE; PROTEIN HAX-1; CORTACTIN; APOPTOSIS; GENE; IDENTIFICATION; CYTOSKELETON AB HAX1 is an ubiquitously expressed human gene. Though a number of cellular and viral proteins are known to interact with HAX1, its function is still not completely understood. On the basis of these identified interaction partners, HAXI seems to play a role in apoptosis and the organization of the cytoskeleton. The cDNAs for human and mouse Hax1 share 86% identity and 80% identity at the protein level, suggesting a similar functional importance. To date, no conclusive data on the tissue specific expression of the murine Hax1 are available and only one interaction partner has been identified. Here, we show a detailed expression analysis for the murine ortholog by RT-PCR, Northern and Western blot. Furthermore, the distribution of Hax1 within different mouse tissues was studied by immunohistochemistry (IHC). In general, we found a good correlation between the results obtained from different detection techniques. Similar to its human counterpart, mouse Hax1 seems to be ubiquitously expressed. At the RNA level, we found the highest expression of Hax1 in liver, kidney and testis. In sharp contrast to the human HAX1 which is highly expressed in skeletal muscle, the mouse ortholog was detected only at very low levels. Using a specific antibody, we detected Hax1 in the majority of mouse tissues by IHC. Interestingly, the most prominent expression of Hax1 was found in epithelial, endothelial and muscle cells. Surprisingly, thymus, spleen and pancreas did not show detectable immunostaining. Furthermore, we have studied the subcellular localisation of Hax1 in a keratinocyte and a neuronal cell line by immunofluorescence. We found Hax1 to be localised mainly in the cytoplasm and detected a partial colocalisation with mitochondria. The results presented here summarize for the first time the expression of the murine Hax1 in different tissues and two cell lines. Further studies will elucidate the functional importance of this protein in individual cell types with respect to structural aspects, cell mobility and apoptosis. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Dusseldorf, Dept Dermatol, D-40225 Dusseldorf, Germany. Vilnius State Univ, Dept Dermatovenereol, Vilnius, Lithuania. Univ Dusseldorf, Inst Umweltmed Forsch, D-40225 Dusseldorf, Germany. NCI, Canc Res Ctr, NIH, Bethesda, MD USA. Univ Munich, Dept Dermatol & Allergy, Munich, Germany. RP Hippe, A (reprint author), Univ Dusseldorf, Dept Dermatol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM hippe@med.uni-duesseldorf.de NR 48 TC 15 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 1 PY 2006 VL 379 BP 116 EP 126 DI 10.1016/j.gene.2006.04.027 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 086TI UT WOS:000240695500013 PM 16814492 ER PT J AU Chen, QR Bilke, S Wei, JS Greer, BT Steinberg, SM Westermann, F Schwab, M Khan, J AF Chen, Qing-Rong Bilke, Sven Wei, Jun S. Greer, Braden T. Steinberg, Seth M. Westermann, Frank Schwab, Manfred Khan, Javed TI Increased WSB1 copy number correlates with its over-expression which associates with increased survival in neuroblastoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID AGGRESSIVE NEUROBLASTOMA; GENOMIC ALTERATIONS; PREDICTION; AMPLIFICATION; TUMORS; MODEL AB Gain of chromosome 17 is the most prevalent genetic abnormality identified in neuroblastoma (NB) and distal 17q gain has prognostic significance in NIB. In this report, we have combined array-based comparative genomic hybridization (A-CGH) and gene expression analysis to investigate gene copy number changes and its impact on the gene expression level as well as their association with prognosis genes located on chromosome 17 in NB tumors. We observed differential gains of chromosome 17 between Stages 4- and 4S tumors. We found that WSB1, mapping to 17q11.1, which was frequently gained in 4S- tumors and not changed in 4- tumors, showed strong correlations between expression level and copy number. Furthermore, the increase of WSB1 gene expression is associated with good outcome in patients with NB of all stages. WSB1 also enhances the prognostic prediction when combined with other current prognostic factors in NB. Our results demonstrate that WSB1 copy number correlates with its expression level and that its high expression associates with good prognosis suggesting a possible role of this gene in the biology of favorable outcome NB. This article contains Supplementary Material available at http://www. interscience.wiIey.com/jpages/1045-2257/suppmat. Published 2006 Wiley-Liss, Inc. C1 Natl Canc Inst, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD 20877 USA. SAIC Frederick Inc, NCI, Adv Biomed Comp Ctr, Frederick, MD USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. German Canc Res Ctr, Dept Tumor Genet, D-6900 Heidelberg, Germany. RP Khan, J (reprint author), Natl Canc Inst, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 FU NCI NIH HHS [N01 CO 12400] NR 22 TC 21 Z9 21 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 2006 VL 45 IS 9 BP 856 EP 862 DI 10.1002/gcc.20349 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 068CM UT WOS:000239349500008 PM 16804916 ER PT J AU Guillier, M Gottesman, S Storz, G AF Guillier, Maude Gottesman, Susan Storz, Gisela TI Modulating the outer membrane with small RNAs SO GENES & DEVELOPMENT LA English DT Review DE Hfq; OmpC; OmpA; sigma(E); OmpR ID SMALL NONCODING RNAS; OMPA MESSENGER-RNA; SMALL REGULATORY RNA; MICF ANTISENSE RNA; ESCHERICHIA-COLI; PROTEIN-A; DEPENDENT REGULATION; GLOBAL ANALYSIS; CELL-ENVELOPE; HFQ AB MicF, one of the first chromosomally encoded regulatory small RNAs (sRNAs) to be discovered, was found to modulate the expression of OmpF, an abundant outer membrane protein. Several recent papers have now shown that this is not an isolated case. At least five other sRNAs also regulate the synthesis of outer membrane porins, and additional sRNAs modulate the expression of other outer membrane proteins. Here we review what is known about these sRNAs and discuss the implications of this regulation. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM susang@helix.nih.gov; storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 NR 62 TC 119 Z9 124 U1 1 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 2006 VL 20 IS 17 BP 2338 EP 2348 DI 10.1101/gad.1457506 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 081FU UT WOS:000240303400003 PM 16951250 ER PT J AU Chen, BSE Sakoda, LC Hsing, AW Rosenberg, PS AF Chen, Bingshu E. Sakoda, Lori C. Hsing, Ann W. Rosenberg, Philip S. TI Resampling-based multiple hypothesis testing procedures for genetic case-control association studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE case-control studies; haplotypes; single nucleotide polymorphsim; permutation test; biliary tract neoplasms; prostaglandin-endoperoxide synthase 2 ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HAPLOTYPE FREQUENCIES; MAXIMUM-LIKELIHOOD; ALZHEIMERS-DISEASE; LINKAGE PHASE; EPIDEMIOLOGY; REPLICATION; POPULATION; FUTURE; POWER AB In case-control studies of unrelated subjects, gene-based hypothesis tests consider whether any tested feature in a candidate gene single nucleotide polymorphisms (SNPs), haplotypes, or both-are associated with disease. Standard statistical tests are available that control the false-positive rate at the nominal level over all polymorphisms considered. However, more powerful tests can be constructed that use permutation resampling to account for correlations between polymorphisms and test statistics. A key question is whether the gain in power is large enough to justify the computational burden. We compared the computationally simple Simes Global Test to the min P test, which considers the permutation distribution of the minimum p-value from marginal tests of each SNP. In simulation studies incorporating empirical haplotype structures in 15 genes, the min P test controlled the type I error, and was modestly more powerful than the Simes test, by 2.1 percentage points on average. When disease susceptibility was conferred by a haplotype, the min P test sometimes, but not always, under-performed haplotype analysis. A resampling-based omnibus test combining the min P and haplotype frequency test controlled the type I error, and closely tracked the more powerful of the two component tests. This test achieved consistent gains in power (5.7 percentage points on average), compared to a simple Bonferroni test of Simes and haplotype analysis. Using data from the Shanghai Biliary Tract Cancer Study, the advantages of the newly proposed omnibus test were apparent in a population-based study of bile duct cancer and polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) gene. Genet. Epidemiol. 30:495-507, 2006. Published 2006 Wiley-Liss, Inc. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. RP Chen, BSE (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,Execut Plaza S,Room 8089, Rockville, MD 20852 USA. EM cheneric@mail.nih.gov OI Chen, Bingshu/0000-0001-6139-0696 FU Intramural NIH HHS NR 32 TC 51 Z9 51 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2006 VL 30 IS 6 BP 495 EP 507 DI 10.1002/gepi.20162 PG 13 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 074ZR UT WOS:000239851900004 PM 16755536 ER PT J AU Valencia-Burton, M Oki, M Johnson, J Seier, TA Kamakaka, R Haber, JE AF Valencia-Burton, Maria Oki, Masaya Johnson, Jean Seier, Tracey A. Kamakaka, Rohinton Haber, James E. TI Different mating-type-regulated genes affect the DNA repair defects of Saccharomyces RAD51, RAD52 and RAD55 mutants SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAK; END-JOINING REPAIR; REPLICATION PROTEIN-A; RECA HOMOLOGS RAD51; CELL-CYCLE; MEIOTIC RECOMBINATION; CLEAVABLE COMPLEXES; ATP HYDROLYSIS; HIGH COPY; CEREVISIAE AB Saccharomyces cerevisiae cells expressing both a- and alpha-mating-type (MAT) genes (termed mating-type heterozygosity) exhibit higher rates of spontaneous recombination and greater radiation resistance than cells expressing only MATa or MAT alpha. MAT heterozygosity suppresses recombination defects of four mutations involved in homologous recombination: complete deletions of RAD55 or RAD57 an ATPase-defective Rad51 mutation (rad51-K191R), and a C-terminal truncation of Rad52, rad52-Delta 327 We investigated the genetic basis of MAT-dependent suppression of these mutants by deleting genes whose expression is controlled by the Mata1-Mat alpha 2 repressor and scoring resistance to both campothecin (CPT) and phleomycin. Haploid rad55 Delta strains became more damage resistant after deleting genes required for nonhomologous end joining (NHEJ), a process that is repressed in MATa/MAT alpha cells. Surprisingly, NHEJ mutations do not suppress CPT sensitivity of rad51-K191R or rad52-Delta 327. However, rad51-K191R is uniquely suppressed by deleting the RME1 gene encoding a repressor of meiosis or its coregulator SIN4; this effect is independent of the meiosis-specific homolog, Dmc1. Sensitivity of rad52-Delta 327 to CPT was unexpectedly increased by the MATa/MAT alpha-repressed gene YGL193C, emphasizing the complex ways in which MAT regulates homologous recombination. The rad52-Delta 327mutation is suppressed by deleting the prolyl isomerase Fpr3, which is not MATregulated. rad55 Delta is also suppressed by deletion of PST2 and/or YBR052C (RFS1, rad55 suppressor), two members of a three-gene family of flavodoxin-fold proteins that associate in a nonrandom fashion with chromatin. All three recombination-defective mutations are made more sensitive by deletions of Rad6 and of the histone deacetylases Rpd3 and Ume6, although these mutations are not themselves CPT or phleomycin sensitive. C1 Brandeis Univ, Rosenstiel Ctr, Waltham, MA 02254 USA. Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. NIH, Unit Chromatin & Transcript, Bethesda, MD 20892 USA. RP Haber, JE (reprint author), Brandeis Univ, Rosenstiel Ctr, 415 S St,Mailstop 029, Waltham, MA 02254 USA. EM haber@brandeis.edu OI Haber, James/0000-0002-1878-0610 FU NIGMS NIH HHS [R37 GM020056, T32 GM007122, R01 GM020056-32, R01 GM020056-33, GM20056, R01 GM020056] NR 65 TC 21 Z9 23 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2006 VL 174 IS 1 BP 41 EP 55 DI 10.1534/genetics.106.058685 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 092YT UT WOS:000241134400005 PM 16782999 ER PT J AU Bibikova, M Chudin, E Wu, B Zhou, LX Garcia, EW Liu, Y Shin, S Plaia, TW Auerbach, JM Arking, DE Gonzalez, R Crook, J Davidson, B Schulz, TC Robins, A Khanna, A Sartipy, P Hyllner, J Vanguri, P Savant-Bhonsale, S Smith, AK Chakravarti, A Maitra, A Rao, M Barker, DL Loring, JF Fan, JB AF Bibikova, Marina Chudin, Eugene Wu, Bonnie Zhou, Lixin Garcia, Eliza Wickham Liu, Ying Shin, Soojung Plaia, Todd W. Auerbach, Jonathan M. Arking, Dan E. Gonzalez, Rodolfo Crook, Jeremy Davidson, Bruce Schulz, Thomas C. Robins, Allan Khanna, Aparna Sartipy, Peter Hyllner, Johan Vanguri, Padmavathy Savant-Bhonsale, Smita Smith, Alan K. Chakravarti, Aravinda Maitra, Anirban Rao, Mahendra Barker, David L. Loring, Jeanne F. Fan, Jian-Bing TI Human embryonic stem cells have a unique epigenetic signature SO GENOME RESEARCH LA English DT Article ID HUMAN BLASTOCYSTS; DNA METHYLATION; IN-VITRO; SPONTANEOUS DIFFERENTIATION; LINES; DERIVATION; MAINTENANCE; GENOME; HYPERMETHYLATION; EPIGENOME AB Human embryonic stem (hES) cells originate during an embryonic period of active epigenetic remodeling. DNA methylation patterns are likely to be critical for their self- renewal and pluripotence. We compared the DNA methylation status of 1536 CpG sites (from 371 genes) in 14 independently isolated hES cell lines with five other cell types: 24 cancer cell lines, four adult stem cell populations, four lymphoblastoid cell lines, five normal human tissues, and an embryonal carcinoma cell line. We found that the DNA methylation profile clearly distinguished the hES cells from all of the other cell types. A subset of 49 CpG sites from 40 genes contributed most to the differences among cell types. Another set of 25 sites from 23 genes distinguished hES cells from normal differentiated cells and can be used as biomarkers to monitor differentiation. Our results indicate that hES cells have a unique epigenetic signature that may contribute to their developmental potential. C1 Illumina Inc, San Diego, CA 92121 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Amer Type Culture Collect, Stem Cell Ctr, Manassas, VA 20108 USA. Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Burnham Inst Med Res, La Jolla, CA 92037 USA. ES Cell Int, Singapore 117610, Singapore. BresaGen Inc, Athens, GA 30605 USA. Reliance Life Sci Pvt Ltd, Bombay 400701, Maharashtra, India. Cellartis AB, S-41346 Gothenburg, Sweden. Theradigm Inc, Baltimore, MD 21227 USA. Cognate Therapeut Inc, Baltimore, MD 21227 USA. RP Fan, JB (reprint author), Illumina Inc, San Diego, CA 92121 USA. EM jfan@illumina.com RI Barker, David/A-5671-2013 FU NCI NIH HHS [R44 CA097851, R44-CA097851] NR 41 TC 183 Z9 197 U1 1 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2006 VL 16 IS 9 BP 1075 EP 1083 DI 10.1101/gr.5319906 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 080HN UT WOS:000240238600001 PM 16899657 ER PT J AU Fyfe, JC Menotti-Raymond, M David, VA Brichta, L Schaffer, AA Agarwala, R Murphy, WJ Wedemeyer, WJ Gregory, BL Buzzell, BG Drummond, MC Wirth, B O'Brien, SJ AF Fyfe, John C. Menotti-Raymond, Marilyn David, Victor A. Brichta, Lars Schaffer, Alejandro A. Agarwala, Richa Murphy, William J. Wedemeyer, William J. Gregory, Brittany L. Buzzell, Bethany G. Drummond, Meghan C. Wirth, Brunhilde O'Brien, Stephen J. TI An similar to 140-kb deletion associated with feline spinal muscular atrophy implies an essential LIX1 function for motor neuron survival SO GENOME RESEARCH LA English DT Article ID RADIATION HYBRID MAP; SINGLE NUCLEOTIDE; CAT GENOME; GENE SMN1; PROTEIN; MUTATION; DISEASE; SMA; IDENTIFICATION; PREDICTION AB The leading genetic cause of infant mortality is spinal muscular atrophy ( SMA), a clinically and genetically heterogeneous group of disorders. Previously we described a domestic cat model of autosomal recessive, juvenile-onset SMA similar to human SMA type III. Here we report results of a whole-genome scan for linkage in the feline SMA pedigree using recently developed species-specific and comparative mapping resources. We identified a novel SMA gene candidate, LIX1, in an similar to 140-kb deletion on feline chromosome A1q in a region of conserved synteny to human chromosome 5q15. Though LIX1 function is unknown, the predicted secondary structure is compatible with a role in RNA metabolism. LIX1 expression is largely restricted to the central nervous system, primarily in spinal motor neurons, thus offering explanation of the tissue restriction of pathology in feline SMA. An exon sequence screen of 25 human SMA cases, not otherwise explicable by mutations at the SMN1 locus, failed to identify comparable LIX1 mutations. Nonetheless, a LIX1-associated etiology in feline SMA implicates a previously undetected mechanism of motor neuron maintenance and mandates consideration of LIX1 as a candidate gene in human SMA when SMN1 mutations are not found. C1 Michigan State Univ, Lab Comparat Med Genet, Dept Microbiol & Mol Genet, Coll Vet Med, E Lansing, MI 48824 USA. NCI, Lab Gen Divers, Ft Detrick, MD 21702 USA. Univ Cologne, Inst Human Genet, Inst Genet, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Texas A&M Univ, Coll Stn, Coll Vet Med & Biomed Sci, Dept Vet Integrated Biosci, College Stn, TX 77843 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. RP Fyfe, JC (reprint author), Michigan State Univ, Lab Comparat Med Genet, Dept Microbiol & Mol Genet, Coll Vet Med, E Lansing, MI 48824 USA. EM fyfe@cvm.msu.edu RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS; NICHD NIH HHS [HD39888] NR 43 TC 30 Z9 30 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2006 VL 16 IS 9 BP 1084 EP 1090 DI 10.1101/gr.5268806 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 080HN UT WOS:000240238600002 PM 16899656 ER PT J AU Setzu, A Lathia, JD Zhao, C Wells, K Rao, MS Ffrench-Constant, C Franklin, RJM AF Setzu, Anna Lathia, Justin D. Zhao, Chao Wells, Karen Rao, Mahendra S. Ffrench-Constant, Charles Franklin, Robin J. M. TI Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells SO GLIA LA English DT Article DE remyelination; inflammation; multiple sclerosis; oligodendrocyte; precursor cell; retina; transplantation ID CENTRAL-NERVOUS-SYSTEM; COMMITTED PROGENITOR CELLS; CNS AGGREGATE CULTURES; MULTIPLE-SCLEROSIS; GENE-EXPRESSION; SPINAL-CORD; TGF-BETA; CHRONIC DEMYELINATION; SCHWANN-CELLS; OPTIC-NERVE AB Inflammation associated with CNS demyelination provides an important stimulus for the activation of endogenous oligodendrocyte precursor cells (OPCs) and subsequent remyelination. This view is largely based on "loss-of-function" studies, whereby remyelination is impaired following depletion of inflammatory cells or mediators. However, "gain-of-function" approaches, asking whether inflammation directly enhances remyelination, have received less attention. We have addressed this issue using a model in which OPCs transplanted into the adult rat retina myelinate retinal ganglion cell axons around the point of injection. Inflammation (characterized by increased expression of the macrophage marker ED1 and the astrocyte marker GFAP, and the up-regulation of multiple cytokines) was induced in the retina by the administration of the TLR-2 ligand zymosan. Myelination, revealed by MBP+ myelin sheaths, was substantially increased when OPCs were injected into the inflamed retina compared to that achieved following transplantation into the normal, noninflamed retina. Our results have important implications for the development of immunomodulatory treatments for acute demyelinating disease and for the therapeutic creation of proremyelination environments in chronic demyelinating disease. (c) 2006 Wiley-Liss, Inc. C1 Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England. Univ Cambridge, Ctr Brain Repair, Cambridge, England. Univ Cambridge, MS Soc Cambridge Ctr Myelin Repair, Cambridge, England. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. NIA, Neurosci Lab, NIH, Baltimore, MD USA. RP Franklin, RJM (reprint author), Univ Cambridge, Dept Vet Med, Madingley Rd, Cambridge CB3 0ES, England. EM rjf1000@cam.ac.uk FU Multiple Sclerosis Society [689] NR 57 TC 113 Z9 114 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2006 VL 54 IS 4 BP 297 EP 303 DI 10.1002/glia.20371 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 070QC UT WOS:000239537300005 PM 16856149 ER PT J AU Tunis, SR Pearson, SD AF Tunis, Sean R. Pearson, Steven D. TI Coverage options for promising technologies: Medicare's 'coverage with evidence development' SO HEALTH AFFAIRS LA English DT Article ID PRACTICAL CLINICAL-TRIALS; DECISION-MAKING; HEALTH-CARE; THERAPY; SUPPORT AB In April 2005 the Centers for Medicare and Medicaid Services (CMS) posted on its Web site a draft guidance document describing a new approach to coverage policy called "coverage with evidence development" (CED). CED offered an option for coverage of promising drugs, biologics, devices, diagnostics, and procedures that would not otherwise meet Medicare's evidentiary standards for being "reasonable and necessary." An updated guidance was posted 12 July 2006, clarifying several key statutory, regulatory, and operational issues. This paper traces the history of this policy approach, explains the rationale behind the policy, and describes the major challenges that will need to be addressed for CED to become an important advance in evidence-based coverage decision making. C1 Ctr Med Technol Policy, San Francisco, CA USA. NIH, Bethesda, MD 20892 USA. RP Tunis, SR (reprint author), Ctr Med Technol Policy, San Francisco, CA USA. EM sean.tunis@netzero.net NR 35 TC 140 Z9 141 U1 0 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SEP-OCT PY 2006 VL 25 IS 5 BP 1218 EP 1230 DI 10.1377/hlthaff.25.5.1218 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 087MJ UT WOS:000240746200004 PM 16966717 ER PT J AU Reynolds, KD Buller, DB Yaroch, AL Maloy, JA Cutter, GR AF Reynolds, Kim D. Buller, David B. Yaroch, Amy L. Maloy, Julie A. Cutter, Gary R. TI Mediation of a middle school skin cancer prevention program SO HEALTH PSYCHOLOGY LA English DT Article DE sun safety; mediation; skin cancer; prevention ID PHYSICAL-ACTIVITY; SUN PROTECTION; VARIABLES; ADOLESCENTS; CHILDREN; INTERVENTIONS; BELIEFS; PROJECT; POPULATION; SUNSCREEN AB This study tested potential mediators of a school-based skin cancer prevention intervention for middle school children (6th-8th grades; N = 1,788). Ten variables were tested on 4 criteria to establish mediation, including (a) intervention related to outcome, (b) intervention related to mediators, (c) mediators related to outcome, and (d) mediated effect statistically significant. Sun-safe behaviors (e.g., sunscreen use) and potential mediators were measured with a self-report questionnaire. All criteria were met for Barriers-Sunscreen, Perceived Self-Efficacy, and Knowledge when the mediators were tested separately. In multiple mediator analyses, barriers to sunscreen use and self-efficacy satisfied Criteria 1-3 but were not statistically significant (Criterion 4). Barriers to sunscreen use, perceived self-efficacy for sun-safe behavior, and knowledge may serve as mediators. C1 Univ So Calif, Inst Hlth Promot & Dis Prevent Res, Alhambra, CA 91803 USA. Cooper Inst, Ctr Hlth Res, Denver, CO USA. Natl Canc Inst, Div Canc Control & Populat Sci, Rockville, MD USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. RP Reynolds, KD (reprint author), Univ So Calif, Inst Hlth Promot & Dis Prevent Res, 1000 S Freemont Ave,Unit 8, Alhambra, CA 91803 USA. EM kdreynol@usc.edu FU NCI NIH HHS [R01 CA079701] NR 59 TC 13 Z9 13 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2006 VL 25 IS 5 BP 616 EP 625 DI 10.1037/0278-6133.25.5.616 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 093BC UT WOS:000241141200009 PM 17014279 ER PT J AU Barth, H Liang, TJ Baumert, TF AF Barth, Heidi Liang, T. Jake Baumert, Thomas F. TI Hepatitis C virus entry: Molecular biology and clinical implications SO HEPATOLOGY LA English DT Review ID ENVELOPE GLYCOPROTEIN E2; B TYPE-I; DENSITY-LIPOPROTEIN RECEPTOR; HUMAN MONOCLONAL-ANTIBODIES; HUMAN HEPATOMA-CELLS; SCAVENGER RECEPTOR; NEUTRALIZING ANTIBODIES; HEPARAN-SULFATE; DC-SIGN; MEMBRANE-FUSION AB With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. A vaccine protecting against HCV infection is not available, and current antiviral therapies are characterized by limited efficacy, high costs, and substantial side effects. Binding of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between virus and the target cell that is required for the initiation of infection. Because this step represents a critical determinant of tissue tropism and pathogenesis, it is a major target for host cell responses such as antibody-mediated virus-neutralization-and a promising target for new antiviral therapy. The recent development of novel tissue culture model systems for the study of the first steps of HCV infection has allowed rapid progress in the understanding of the molecular mechanisms of HCV binding and entry. This review summarizes the impact of recently identified viral and host cell factors for HCV attachment and entry. Clinical implications of this important process for the pathogenesis of HCV infection and novel therapeutic interventions are discussed. C1 Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Strasbourg 1, INSERM U748, F-67070 Strasbourg, France. RP Barth, H (reprint author), Univ Freiburg, Dept Med 2, Hugstetter Str 55, D-79106 Freiburg, Germany. EM Thomas.Baumert@uniklinik-freiburg.de RI Acorsi, Rayanne/H-6066-2016; Lopes Lera, Daniele/H-6081-2016; Vieira Teixeira, Jorge Juarez/H-6495-2016; MOREIRA NETO, LUIZ JORGE/H-6588-2016; OLIVEIRA, WELLINGTON/H-6591-2016; Borges Padilha Ferreira, Fabiana/H-6597-2016; Beletini, Lucimara Fatima/H-6083-2016; Cristina Ferreira, Erika /H-6607-2016 OI MOREIRA NETO, LUIZ JORGE/0000-0002-7407-4120; FU Intramural NIH HHS NR 103 TC 83 Z9 91 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2006 VL 44 IS 3 BP 527 EP 535 DI 10.1002/hep.21321 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080IU UT WOS:000240241900002 PM 16941688 ER PT J AU Yim, SH Shah, Y Tomita, S Morris, HD Gavrilova, O Lambert, G Ward, JM Gonzalez, FJ AF Yim, Sun Hee Shah, Yatrik Tomita, Shuhei Morris, H. Douglas Gavrilova, Oksana Lambert, Gilles Ward, Jerrold M. Gonzalez, Frank J. TI Disruption of the Arnt gene in endothelial cells causes hepatic vascular defects and partial embryonic lethality in mice SO HEPATOLOGY LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; INDUCIBLE FACTOR 1-ALPHA; AH RECEPTOR; CONDITIONAL DISRUPTION; DEFICIENT MICE; PROTEIN ARNT; IN-VIVO; EXPRESSION; MOUSE; HIF-1-ALPHA AB Vascular endothelial cells (ECs) play a critical role in angiogenesis and organogenesis, especially in embryonic liver development. Hypoxia-inducible transcription factors (Hifs) are a key trigger of hypoxic signals, a primary stimulus of angiogenesis. The aryl hydrocarbon receptor nuclear translocator (Arnt), also called Hif-1 beta, serves as an obligate heterodimerization partner of Hif-1 alpha and Hif-2 alpha. Using Cre-Lox technology, the mouse Arnt gene was specifically disrupted in endothelial cells. The resulting mice, designated Arnt(Delta EC), developed impaired hepatic vasculature, liver necrosis, and degenerative lesions in cardiac myocytes at the late embryonic stage (E16.5-E18.5), leading to approximately 90% neonatal lethality. Low serum glucose, downregulation of glucose transporter-1 and glucose-6-phosphatase mRNA, and hepatocyte proliferation were observed in Arnt(Delta EC) embryos. Magnetic resonance imaging on E16.5 embryonic livers revealed that Arnt(Delta EC) mice had a significant volume of avascular region. Arnt(Delta EC) mice that survived to the adult stage were fertile, showed normal behavioral activity, but had smaller livers with mild portal fibrosis, dilated blood vessels, abnormal collagen accumulation, and remarkable iron deposition. Arnt(Delta EC) mice had reduced adiposity, impaired serum lipid homeostasis, and a higher respiratory exchange ratio, indicating they utilized relatively more carbohydrates than their Arnt(F/F) counterparts. In conclusion, endothelial Arnt plays a pivotal role in embryonic liver development. Adult Arnt(Delta EC) mice carrying embryonic hepatic defects developed what was possibly an early stage of cirrhosis with consequences of limited oxygen availability and altered lipid metabolism. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NINDS, NMR Facil, NIH, Bethesda, MD 20892 USA. NIDDKD, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. INSERM, U539, Nantes, France. Univ Tokushima, Inst Genome Res, Div Expt Immunol, Tokushima 770, Japan. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005708-14] NR 33 TC 29 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2006 VL 44 IS 3 BP 550 EP 560 DI 10.1002/hep.21284 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080IU UT WOS:000240241900005 PM 16941684 ER PT J AU Puig, M Mihalik, K Tilton, JC Williams, O Merchlinsky, M Connors, M Feinstone, SM Major, ME AF Puig, Montserrat Mihalik, Kathleen Tilton, John C. Williams, Ollie Merchlinsky, Michael Connors, Mark Feinstone, Stephen M. Major, Marian E. TI CD4+ immune escape and subsequent T-cell failure following chimpanzee immunization against hepatitis C virus SO HEPATOLOGY LA English DT Article ID VIRAL CLEARANCE; NONSTRUCTURAL PROTEIN-3; RECOVERED CHIMPANZEES; NEUTRALIZING ANTIBODY; PLUS RIBAVIRIN; INFECTION; RESPONSES; HCV; PERSISTENCE; CD4(+) AB Hepatitis C is a major cause of chronic liver disease, with 170 million individuals infected worldwide and no available vaccine. We analyzed the effects of an induced T-cell response in 3 chimpanzees, targeting nonstructural proteins in the absence of neutralizing antibodies. In all animals the specific T-cell response modified the outcome of infection, producing a 10- to 1,000-fold reduction in peak virus titers. The challenge of 2 immunized animals that had been previously exposed to hepatitis C virus resulted in subclinical infections. Immune responses in the third animal, naive prior to immunization, limited viral replication immediately, evidenced by a 30-fold reduction in virus titer by week 2, declining to a nonquantifiable level by week 6. After 10 weeks of immunological control, we observed a resurgence of virus, followed by progression to a persistent infection. Comparing virus evolution with T-cell recognition, we demonstrated that: (i) resurgence was concomitant with the emergence of new dominant viral populations bearing single amino acid changes in the NS3 and NS5A regions, (ii) these mutations resulted in a loss of CD4+ T-cell recognition, and (iii) subsequent to viral resurgence and immune escape a large fraction of NS3-specific T cells became impaired in their ability to secrete IFN-gamma and proliferate. In contrast, NS3-specific responses were sustained in the recovered/immunized animals presenting with subclinical infections. In conclusion, viral escape from CD4+ T cells can result in the eventual failure of an induced T-cell response that initially controls infection. Vaccines that can induce strong T-cell responses prior to challenge will not necessarily prevent persistent HCV infection. C1 US FDA, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Viral Dis Lab, Bethesda, MD USA. RP Major, ME (reprint author), US FDA, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bldg 29A-Room 1D10-HFM,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marian.major@fda.hhs.gov FU NCI NIH HHS [CA85883] NR 50 TC 47 Z9 48 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2006 VL 44 IS 3 BP 736 EP 745 DI 10.1002/hep.21319 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080IU UT WOS:000240241900025 PM 16941702 ER PT J AU LaRusso, NF Shneider, BL Black, D Gores, GJ James, SP Doo, E Hoofnagle, JH AF LaRusso, Nicholas F. Shneider, Benjamin L. Black, Dennis Gores, Gregory J. James, Stephen P. Doo, Edward Hoofnagle, Jay H. TI Primary sclerosing cholangitis: Summary of a workshop SO HEPATOLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; INFLAMMATORY-BOWEL-DISEASE; ORTHOTOPIC LIVER-TRANSPLANTATION; SINGLE-CENTER EXPERIENCE; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; DIFFERENT IMMUNOSUPPRESSIVE REGIMENS; DOSE URSODEOXYCHOLIC ACID; PLACEBO-CONTROLLED TRIAL; BILE-DUCT STRICTURES; TOLL-LIKE RECEPTOR-3 AB Primary sclerosing cholangitis (PSC) is a rare but important liver disease that leads to cirrhosis and need for liver transplantation in a high proportion of cases. The disease occurs in approximately I per 100,000 population per year, usually presents in adulthood, and affects men more often than women. Typical serum biochemical results, autoantibodies and liver biopsy are suggestive but not diagnostic of PSC, the diagnosis requiring cholangiographic demonstration of stricturing and dilatation of the intra- and/or extra-hepatic bile ducts. The natural history of PSC is variable, the average survival being 12 to 17 years. The cause of PSC is stiff unknown. Although considered an autoimmune disease, PSC has several atypical features and a strong genetic component. The therapy of PSC is unsatisfactory. Standard doses of ursodeoxycholic acid (LTDCA) lead to improvements in biochemical abnormalities but not in histology, cholangiographic appearance or survival. Several innovative therapies have been tried in PSC, but with scant evidence of benefit. For patients with high grade strictures, endoscopic dilatation is beneficial. Liver transplantation is successful for end-stage liver disease due to PSC and improves survival. PSC may recur after transplantation but is rarely progressive. The most dreaded complication of PSC is cholangiocarcinoma. Diagnosis of this highly malignant tumor is difficult, and there are no biomarkers for its early detection. Liver transplantation for cholangiocarcinoma has an exceedingly poor outcome, although transplantation with neoadjuvant chemoirradiation holds promise in selected patients. Thus, significant opportunities remain for basic and clinical research into the cause, natural history, and therapy of PSC. C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Internal Med, Rochester, MN USA. Mt Sinai Sch Med, Div Pediat Hepatol, New York, NY USA. Univ Tennessee, Hlth Sci Ctr, Childrens Fdn Res Ctr, Memphis, TN USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A27A,31 Ctr Dr, Bethesda, MD 20892 USA. EM hoofnaglej@extra.niddk.nih.gov NR 197 TC 139 Z9 144 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2006 VL 44 IS 3 BP 746 EP 764 DI 10.1002/hep.21337 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 080IU UT WOS:000240241900026 PM 16941705 ER PT J AU Wang, SS Cozen, W Severson, RK Hartge, P Cerhan, JR Davis, S Welch, R Rothman, N Chanock, SJ AF Wang, Sophia S. Cozen, Wendy Severson, Richard K. Hartge, Patricia Cerhan, James R. Davis, Scott Welch, Robert Rothman, Nathaniel Chanock, Stephen J. TI Cyclin D1 splice variant and risk for non-Hodgkin lymphoma SO HUMAN GENETICS LA English DT Article ID POLYMORPHISM; GENE AB To investigate the role of cell cycle gene variations in lymphomagenesis, we evaluated associations (odds ratios [OR] and 95% confidence intervals [CI]) in polymorphisms from seven candidate genes in 1,172 non-Hodgkin lymphoma (NHL) cases and 982 population-based controls. The cyclin D1 (CCND1) splice variant G870A (rs603965) increased NHL risk (ORAA = 1.4, 95% CI = 1.1-1.8, P-trend = 0.021), which was consistent for four B-cell subtypes. As CCND1 expression indicates poor NHL prognosis, our results, if true, would support its potentially dual importance in NHL etiology and survival. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. NCI, Adv Technol Ctr, Core Genotyping Facil, Gaithersburg, MD USA. Univ Iowa, Iowa City, IA USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Executive Blvd,EPS MSC 7234, Rockville, MD 20892 USA. EM wangso@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [N01-PC-65064, N01-PC-67008, N02-PC-71105, N01-PC-67009, N01-PC-67010] NR 10 TC 18 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 2006 VL 120 IS 2 BP 297 EP 300 DI 10.1007/s00439-006-0212-3 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 073GF UT WOS:000239730300017 PM 16783567 ER PT J AU Li, YH Grupe, A Rowland, C Nowotny, P Kauwe, JSK Smemo, S Hinrichs, A Tacey, K Toombs, TA Kwok, S Catanese, J White, TJ Maxwell, TJ Hollingworth, P Abraham, R Rubinsztein, DC Brayne, C Wavrant-De Vrieze, F Hardy, J O'Donovan, M Lovestone, S Morris, JC Thal, LJ Owen, M Williams, J Goate, A AF Li, Yonghong Grupe, Andrew Rowland, Charles Nowotny, Petra Kauwe, John S. K. Smemo, Scott Hinrichs, Anthony Tacey, Kristina Toombs, Timothy A. Kwok, Shirley Catanese, Joseph White, Thomas J. Maxwell, Taylor J. Hollingworth, Paul Abraham, Richard Rubinsztein, David C. Brayne, Carol Wavrant-De Vrieze, Fabienne Hardy, John O'Donovan, Michael Lovestone, Simon Morris, John C. Thal, Leon J. Owen, Michael Williams, Julie Goate, Alison TI DAPK1 variants are associated with Alzheimer's disease and allele-specific expression SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENETIC ASSOCIATION; HAPLOTYPE RECONSTRUCTION; GENOME SCREEN; ONSET; DEATH; APOPTOSIS; LINKAGE; ABCA1; SCAN; SUSCEPTIBILITY AB Genetic factors play an important role in the etiology of late-onset Alzheimer's disease (LOAD). We tested gene-centric single nucleotide polymorphisms (SNPs) on chromosome 9 and identified two SNPs in the death-associated protein kinase, DAPK1, that show significant association with LOAD. SNP rs4878104 was significantly associated with LOAD in our discovery case-control sample set (WU) and replicated in each of two initial validation case-control sample sets (P < 0.05, UK1, SD). The risk-allele frequency of this SNP showed a similar direction in three other case-control sample sets. A meta-analysis of the six sample sets combined, totaling 2012 cases and 2336 controls, showed an allelic P-value of 0.0016 and an odds ratio (OR) of 0.87 (95%CI: 0.79-0.95). Minor allele homozygotes had a consistently lower risk than major allele homozygotes in the discovery and initial two replication sample sets, which remained significant in the meta-analysis of all six sample sets (OR=0.7, 95%CI: 0.58-0.85), whereas the risk for heterozygous subjects was not significantly different from that of major allele homozygotes. A second SNP, rs4877365, which is in high linkage disequilibrium with rs4878104 (r(2)=0.64), was also significantly associated with LOAD (meta P=0.0017 in the initial three sample sets). Furthermore, DAPK1 transcripts show differential allelic gene expression, and both rs4878104 and rs4877365 were significantly associated with DAPK1 allele-specific expression (P=0.015 to < 0.0001). These data suggest that genetic variation in DAPK1 modulates susceptibility to LOAD. C1 Celera Diagnost, Alameda, CA 94502 USA. Washington Univ, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Dept Genet & Biol, St Louis, MO 63110 USA. Cardiff Univ, Wales Coll Med, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales. Cardiff Univ, Wales Coll Med, Biostat & Bioinformat Unit, Cardiff CF14 4XN, S Glam, Wales. Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2XY, England. Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. Inst Psychiat, Univ London Kings Coll, MRC Ctr Neurodegenerat Res, Dept Old Age Psychiat, London SE5 8AF, England. Inst Psychiat, Univ London Kings Coll, MRC Ctr Neurodegenerat Res, Dept Neurosci, London SE5 8AF, England. Natl Inst Aging, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Li, YH (reprint author), Celera Diagnost, 1401 Harbor Bay Pkwy, Alameda, CA 94502 USA. EM yonghong.li@celeradiagnostics.com RI Lovestone, Simon/E-8725-2010; Kauwe, John/B-2034-2009; turton, miranda/F-4682-2011; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; OI Kauwe, John/0000-0001-8641-2468; O'Donovan, Michael/0000-0001-7073-2379 FU Intramural NIH HHS; Medical Research Council [G0300429, G0701075]; NHGRI NIH HHS [T32 HG00045]; NIA NIH HHS [P01 AG03991, P50 AG05131, P50 AG05681, R01 AG16208]; NIGMS NIH HHS [GM065509] NR 48 TC 76 Z9 76 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2006 VL 15 IS 17 BP 2560 EP 2568 DI 10.1093/hmg/ddl178 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 075RB UT WOS:000239901800003 PM 16847012 ER PT J AU Wang, LX Lin, CM Lopreiato, JO Aladjem, MI AF Wang, Lixin Lin, Chii Mei Lopreiato, Joseph O. Aladjem, Mirit I. TI Cooperative sequence modules determine replication initiation sites at the human beta-globin locus SO HUMAN MOLECULAR GENETICS LA English DT Article ID DNA-UNWINDING ELEMENT; ORIGIN; TRANSCRIPTION; BINDING; CHROMOSOME; CELLS AB The human beta globin locus contains two adjacent replicators, each capable of initiating DNA replication when transferred from its native locus to ectopic sites. Here, we report a detailed analysis of the sequence requirements for replication initiation from these replicators. In both replicators, initiation required a combination of an asymmetric purine:pyrimidine sequence and several AT-rich stretches. Modules from the two replicators could combine to initiate replication. AT-rich sequences were essential for replicator activity: a low frequency of initiation was observed in DNA fragments that included a short stretch of AT-rich sequences, whereas inclusion of additional AT-rich stretches increased initiation efficiency. By contrast, replication initiated at a low level without the asymmetric purine:pyrimidine modules but they were required in synergy to achieve efficient initiation. These data support a combinatorial model for replicator activity and suggest that the initiation of DNA replication requires interaction between at least two distinct sequence modules. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Aladjem, MI (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, 37 Convent Dr, Bethesda, MD 20892 USA. EM aladjemm@mail.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU Intramural NIH HHS NR 30 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2006 VL 15 IS 17 BP 2613 EP 2622 DI 10.1093/hmg/ddl187 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 075RB UT WOS:000239901800007 PM 16877501 ER PT J AU Goudeau, B Rodrigues-Lima, F Fischer, D Casteras-Simon, M Sambuughin, N de Visser, M Laforet, P Ferrer, X Chapon, F Sjoberg, G Kostareva, A Sejersen, T Dalakas, MC Goldfarb, LG Vicart, P AF Goudeau, Bertrand Rodrigues-Lima, Fernando Fischer, Dirk Casteras-Simon, Monique Sambuughin, Nyamkhishig de Visser, Marianne Laforet, Pascal Ferrer, Xavier Chapon, Francoise Sjoberg, Gunnar Kostareva, Anna Sejersen, Thomas Dalakas, Marinos C. Goldfarb, Lev G. Vicart, Patrick TI Variable pathogenic potentials of mutations located in the desmin alpha-helical domain SO HUMAN MUTATION LA English DT Article DE myofibrillar myopathy; MFM; distal myopathy; desmin-related myopathy; DRM; desminopathy; cardiomyopathy; desmin gene mutations; DES ID INTERMEDIATE-FILAMENT CHAINS; SKELETAL MYOPATHY; SEQUENCE; PROTEINS; GENE; MITOCHONDRIA; CYTOSKELETON; DISEASE; MUSCLE; MODEL AB Mutations in the desmin gene have been recognized as a cause of desminopathy, a familial or sporadic disorder characterized by skeletal muscle weakness, often associated with cardiomyopathy or respiratory insufficiency. Distinctive histopathologic features include aberrant intracytoplasmic accumulation of desmin (DES). We present here comparative phenotypic, molecular, and functional characteristics of four novel and three previously reported, but not fully characterized, desmin mutations localized in desmin alpha-helical domain. The results indicate that the c.638C > T (p.A213V), c.1178A > T (p.N393I), and to some extent the c.1078G > C (p.A360P) mutations exhibit pathogenic potentials only if combined with other mutations in desmin or other genes and should therefore be considered conditionally pathogenic. The c.1009G > C (p.A337P), c.1013T > G (p.L338R), c.1195G > T (p.D399Y), and c.1201G > A (p.E401K) mutations make desmin filaments dysfunctional and are capable of causing disease. The pathogenic potentials of desmin mutations correlate with the type and location of the disease-associated mutations in the relatively large and structurally and functionally complex desmin molecule. Mutations within the highly conserved alpha-helical structures are especially damaging since the integrity of the alpha-helix is critical for desmin filament assembly and stability. C1 Univ Paris 07, UFR Biochim, F-75005 Paris, France. Univ Paris 07, EA1553, F-75005 Paris, France. Univ Paris 07, EA300, F-75005 Paris, France. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. Univ Amsterdam, Dept Neurol, Med Ctr, Amsterdam, Netherlands. Grp Hosp Pitie Salpetriere, INSERM, U582, Inst Myol, F-75634 Paris, France. Univ Victor Segalen, Serv Neuropathol, Bordeaux, France. CHU Caen, Lab Neuropathol, F-14000 Caen, France. Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden. Karolinska Inst, Ctr Mol Med, Stockholm, Sweden. Pavlov Med Univ, Dept Internal Med, St Petersburg, Russia. RP Vicart, P (reprint author), Univ Paris 07, UFR Biochim, Tour 42,4eme Etage,Case 7006,7 Denis Diderot,2 Pl, F-75005 Paris, France. EM patrick.vicart@paris7.jussieu.fr OI Kostareva, Anna/0000-0002-9349-6257; Sejersen, Thomas/0000-0001-5961-7097 NR 36 TC 30 Z9 32 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD SEP PY 2006 VL 27 IS 9 BP 906 EP 913 DI 10.1002/humu.20351 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 076PK UT WOS:000239970000007 PM 16865695 ER PT J AU Abrahams, VM Schaefer, TM Fahey, JV Visintin, I Wright, JA Aldo, PB Romero, R Wira, CR Mor, G AF Abrahams, Vikki M. Schaefer, Todd M. Fahey, John V. Visintin, Irene Wright, Jacqueline A. Aldo, Paulomi B. Romero, Roberto Wira, Charles R. Mor, Gil TI Expression and secretion of antiviral factors by trophoblast cells following stimulation by the TLR-3 agonist, Poly(I : C) SO HUMAN REPRODUCTION LA English DT Article DE antimicrobial; infection; placenta; pregnancy; Toll-like receptor ID TOLL-LIKE RECEPTORS; INTERFERON-PRODUCTION; 2',5'-OLIGOADENYLATE SYNTHETASE; DIFFERENTIAL REGULATION; PLACENTAL TISSUES; INNATE IMMUNITY; CUTTING EDGE; TRIMESTER; PREGNANCY; VIRUS AB BACKGROUND: During pregnancy, the placenta may become exposed to micro-organisms, such as viruses, which may pose a substantial threat to the embryo/fetus well-being. Recent insight into the immunological capabilities of the trophoblast suggests that the placenta may function as an active barrier by recognizing and responding to pathogens through Toll-like receptors (TLRs). METHODS: The objective of this study was to determine whether the engagement of TLR-3 with viral dsRNA by first-trimester trophoblast could induce the production of factors necessary to generate an antiviral response. Therefore, trophoblast cells were exposed to the TLR-3 agonist, Poly(I : C). RESULTS: We report that following stimulation with Poly(I : C), first-trimester trophoblast cells produce interferon beta (IFN beta) and secretory leukocyte protease inhibitor (SLPI), as well as the intracellular factors 2',5'-oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). This response is TLR-3 specific because the TLR-4 ligand, lipopolysaccharide (LPS), had no effect on the production of these antimicrobial factors. Furthermore, we describe a positive feedback mechanism in which IFN beta enhances the antiviral response by promoting the production of OAS, MxA and APOBEC3G. CONCLUSIONS: These findings suggest that trophoblast cells are able to recognize and specifically respond to viral products in a highly regulated fashion and that the placenta may be pivotal in the control of viral infections at the maternal-fetal interface. C1 Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. Dartmouth Coll Sch Med, Dept Physiol, Lebanon, NH USA. NICHHD, Perinatol Res Branch, Bethesda, MD USA. NICHHD, Perinatol Res Branch, Detroit, MI USA. RP Abrahams, VM (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. EM vikki.abrahams@yale.edu; gil.mor@yale.edu FU Intramural NIH HHS; NIAID NIH HHS [AI51877]; NICHD NIH HHS [2N01HD23342, R01HD049446-01] NR 42 TC 60 Z9 67 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD SEP PY 2006 VL 21 IS 9 BP 2432 EP 2439 DI 10.1093/humrep/del178 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 083CH UT WOS:000240433000036 PM 16751646 ER PT J AU Leenen, FHH Nwachuku, CE Black, HR Cushman, WC Davis, BR Simpson, LM Alderman, MH Atlas, SA Basile, JN Cuyjet, AB Dart, R Felicetta, JV Grimm, RH Haywood, LJ Jafri, SZA Proschan, MA Thadani, U Whelton, PK Wright, JT AF Leenen, Frans H. H. Nwachuku, Chuke E. Black, Henry R. Cushman, William C. Davis, Barry R. Simpson, Lara M. Alderman, Michael H. Atlas, Steven A. Basile, Jan N. Cuyjet, Aloysius B. Dart, Richard Felicetta, James V. Grimm, Richard H. Haywood, L. Julian Jafri, Syed Z. A. Proschan, Michael A. Thadani, Udho Whelton, Paul K. Wright, Jackson T. CA ALLHAT Collaborative Res Grp TI Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial SO HYPERTENSION LA English DT Article DE antihypertensive therapy; hypertension, detection and control; calcium channel blockers; angiotensin-converting enzyme; cardiovascular diseases; stroke; heart failure ID BLOOD-PRESSURE; CARDIOVASCULAR EVENTS; ELDERLY-PATIENTS; OLDER ADULTS; MORTALITY; DISEASE; ALLHAT; MORBIDITY; OUTCOMES; HEALTH AB The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker-initiated therapy in older hypertensive individuals. Patients were randomized to amlodipine (n=9048) or lisinopril (n=9054). The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infarction, analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (CVD), end-stage renal disease ( ESRD), cancer, and gastrointestinal bleeding. Mean follow-up was 4.9 years. Blood pressure control was similar in nonblacks, but not in blacks. No significant differences were found between treatment groups for the primary outcome, all-cause mortality, ESRD, or cancer. Stroke rates were higher on lisinopril in blacks (RR=1.51, 95% CI 1.22 to 1.86) but not in nonblacks (RR=1.07, 95% CI 0.89 to 1.28), and in women (RR=1.45, 95% CI 1.17 to 1.79), but not in men (RR=1.10, 95% CI 0.92 to 1.31). Rates of combined CVD were higher (RR=1.06, 95% CI 1.00 to 1.12) because of higher rates for strokes, peripheral arterial disease, and angina, which were partly offset by lower rates for heart failure (RR=0.87, 95% CI 0.78 to 0.96) on lisinopril compared with amlodipine. Gastrointestinal bleeds and angioedema were higher on lisinopril. Patients with and without baseline coronary heart disease showed similar outcome patterns. We conclude that in hypertensive patients, the risks for coronary events are similar, but for stroke, combined CVD, gastrointestinal bleeding, and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy. Some, but not all, of these differences may be explained by less effective blood pressure control in the lisinopril arm. C1 Univ Ottawa, Hypertens Unit, Inst Heart, Ottawa, ON K1Y 4W7, Canada. NHLBI, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Vet Affairs Med Ctr, Memphis, TN USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Vet Affairs Med Ctr, Bronx, NY USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Univ Med & Dent New Jersey, Newark, NJ USA. Carl T Hayden VA Med Ctr, Phoenix, AZ USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. Vet Affairs Med Ctr, Fargo, ND USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Leenen, FHH (reprint author), Univ Ottawa, Hypertens Unit, Inst Heart, H-360,40 Ruskin St, Ottawa, ON K1Y 4W7, Canada. EM fleenen@ottawaheart.ca FU NHLBI NIH HHS [N01-HC-35130] NR 33 TC 73 Z9 84 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2006 VL 48 IS 3 BP 374 EP 384 DI 10.1161/01.HYP.0000231662.77359.de PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 124ZN UT WOS:000243411400012 PM 16864749 ER PT J AU Li, J Manry, MT Narasimha, PL Yu, CH AF Li, Jiang Manry, Michael T. Narasimha, Pramod L. Yu, Changhua TI Feature selection using a piecewise linear network SO IEEE TRANSACTIONS ON NEURAL NETWORKS LA English DT Article DE feature selection; regression; piecewise linear network (PLN); orthonormal least squares (OLS); floating search ID FEATURE SUBSET-SELECTION; FEEDFORWARD NEURAL-NETWORKS; ORTHOGONAL LEAST-SQUARES; INDEPENDENT COMPONENT ANALYSIS; VARIABLE SELECTION; HIDDEN UNITS; ALGORITHM; REGRESSION; INFORMATION; IDENTIFICATION AB We present an efficient feature selection algorithm for the general regression problem, which utilizes a piecewise linear orthonormal least squares (OLS) procedure. The algorithm 1) determines an appropriate piecewise linear network (PLN) model for the given data set, 2) applies the OLS procedure to the PLN model, and 3) searches for useful feature subsets using a floating search algorithm. The floating search prevents the "nesting effect." The proposed algorithm is computationally very efficient because only one data pass is required. Several examples are given to demonstrate the effectiveness of the proposed algorithm. C1 Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. Univ Texas, Dept Elect Engn, Arlington, TX 76019 USA. Fastvdo LLC, Columbia, MD 21046 USA. RP Li, J (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM li@wcn.uta.edu; manry@uta.edu NR 57 TC 26 Z9 26 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1045-9227 J9 IEEE T NEURAL NETWOR JI IEEE Trans. Neural Netw. PD SEP PY 2006 VL 17 IS 5 BP 1101 EP 1115 DI 10.1109/TNN.2006.877531 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 084DH UT WOS:000240511600001 PM 17001973 ER PT J AU Watanabe, T Kitani, A Murray, PJ Wakatsuki, Y Fuss, IJ Strober, W AF Watanabe, Tomohiro Kitani, Atsushi Murray, Peter J. Wakatsuki, Yoshio Fuss, Ivan J. Strober, Warren TI Nucleotide binding oligomerization domain 2 deficiency leads to dysregulated TLR2 signaling and induction of antigen-specific colitis SO IMMUNITY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; CROHNS-DISEASE; T-CELLS; MEDIATED-IMMUNITY; ESCHERICHIA-COLI; LEISHMANIA-MAJOR; KAPPA-B; NOD2; MICE AB In this study, we determined conditions leading to the development of colitis in mice with nucleotide binding oligomerization domain 2 (NOD2) deficiency, a susceptibility factor in Crohn's disease. We found that NOD2-deficient antigen-presenting cells (APCs) produced increased amounts of interleukin (IL)-12 in the presence of ovalbumin (OVA) peptide and peptidoglycan or recombinant E. coli that express OVA peptide (ECOVA). Furthermore, these APCs elicited heightened interferon-gamma (IFN-gamma) responses from cocultured OVA-specific CD4(+) T cells. We then demonstrated that NOD2-deficient mice adoptively transferred OVA-specific CD4(+) T cells and that administered intrarectal ECOVA developed colitis associated with the expansion of OVA-specific CD4(+) T cells producing IFN-gamma. Importantly, this colitis was highly dependent on Toll-like receptor 2 (TLR2) function since it was suppressed in NOD2 and TLR2 double-deficient mice. Thus, NOD2-deficient mice become susceptible to colitis as a result of increased TLR2 responses when they have the capacity to respond to an antigen expressed by mucosal bacteria. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Kyoto Univ, Grad Sch Med, Dept Clin Bioregulatory Sci, Sakyo Ku, Kyoto 6068507, Japan. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bldg 10-CRC,Room 5W3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 38 TC 143 Z9 146 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2006 VL 25 IS 3 BP 473 EP 485 DI 10.1016/j.immuni.2006.06.018 PG 13 WC Immunology SC Immunology GA 089ED UT WOS:000240862200015 PM 16949315 ER PT J AU Yim, JJ Adams, AA Kim, JH Holland, SM AF Yim, Jae-Joon Adams, Amelia A. Kim, Ju Han Holland, Steven M. TI Evolution of an intronic microsatellite polymorphism in Toll-like receptor 2 among primates SO IMMUNOGENETICS LA English DT Article DE Toll-like receptor 2; microsatellite polymorphism; evolution; primates ID TOLL-LIKE RECEPTOR-2; CELL WALL COMPONENTS; INNATE IMMUNITY; MYCOBACTERIUM-TUBERCULOSIS; SEQUENCE EVOLUTION; CUTTING EDGE; RECOGNITION; FAMILY; GENE; DNA AB Nonhuman primates express varying responses to Mycobacterium tuberculosis: New World monkeys appear to be resistant to tuberculosis (TB) while Old World monkeys seem to be particularly susceptible. The aim of this study was to elucidate the presence of the regulatory guanine-thymine (GT) repeat polymorphisms in intron 2 of Toll-like receptor 2 (TLR2) associated with the development of TB in humans and to determine any variations in these microsatellite polymorphisms in primates. We sequenced the region encompassing the regulatory GT repeat microsatellites in intron 2 of TLR2 in 12 different nonhuman primates using polymerase chain reaction amplification, TA cloning, and automatic sequencing. The nonhuman primates included for this study were as follows: chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), Celebes ape (Macaca nigra), rhesus monkey (Macaca mulatta), pigtail macaque (Macaca nemestrina), patas monkey (Erythrocebus patas), spider monkey (Ateles geoffroyi), Woolly monkey (Lagothrix lagotricha), tamarin (Saguinus labiatus), and ring-tailed lemur (Lemur catta). Nucleotide sequences encompassing the regulatory GT repeat region are similar across species and are completely conserved in great apes. However, Old World monkeys lack GT repeats altogether, while New World monkeys and ring-tailed lemurs have much more complex structures around the position of the repeats. In conclusion, the genetic structures encompassing the regulatory GT repeats in intron 2 of human TLR2 are similar among nonhuman primates. The sequence is most conserved in New World monkeys and less in Old World monkeys. C1 NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, SNUBI, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Internal Med, Div Pulm & Crit Care Med, Seoul 151, South Korea. Seoul Natl Univ, Coll Med, Lung Inst Med Res Ctr, Seoul, South Korea. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bldg 10,CRC B3-4141,10 Ctr Dr,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov RI Kim, Ju Han/E-5983-2012; Yim, Jae Joon/J-2783-2012 NR 36 TC 7 Z9 8 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 2006 VL 58 IS 9 BP 740 EP 745 DI 10.1007/s00251-006-0141-2 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 081KT UT WOS:000240317200004 PM 16912902 ER PT J AU Donohue, KB Grant, JM Tewalt, EF Palmer, DC Theoret, MR Restifo, NP Norbury, CC AF Donohue, Keri B. Grant, Jean M. Tewalt, Eric F. Palmer, Douglas C. Theoret, Marc R. Restifo, Nicholas P. Norbury, Christopher C. TI Cross-priming utilizes antigen not available to the direct presentation pathway SO IMMUNOLOGY LA English DT Article DE antigen presentation; antigen processing; cytotoxic T cells; major histocompatibility complex; transgenic mice ID HEAT-SHOCK PROTEINS; CD8(+) T-CELLS; NEWLY SYNTHESIZED PROTEINS; MINOR H-ANTIGENS; DENDRITIC CELLS; IN-VIVO; GLUCOCORTICOID-RECEPTOR; CHAPERONE MACHINERY; PRESENTING CELLS; APOPTOTIC CELLS AB CD8(+) T cells play a crucial role in protective immunity to viruses and tumours. Antiviral CD8(+) T cells are initially activated by professional antigen presenting cells (pAPCs) that are directly infected by viruses (direct-priming) or following uptake of exogenous antigen transferred from virus-infected or tumour cells (cross-priming). In order to efficiently target each of these antigen-processing pathways during vaccine design, it is necessary to delineate the properties of the natural substrates for either of these antigen-processing pathways. In this study, we utilized a novel T-cell receptor (TCR) transgenic mouse to examine the requirement for both antigen synthesis and synthesis of other cellular factors during direct or cross-priming. We found that direct presentation required ongoing synthesis of antigen, but that cross-priming favoured long-lived antigens and did not require ongoing antigen production. Even after prolonged blockade of protein synthesis in the donor cell, cross-priming was unaffected. In contrast, direct-presentation was almost undetectable in the absence of antigen neosynthesis and required ongoing protein synthesis. This suggests that the direct- and cross-priming pathways may utilize differing pools of antigen, an observation that has far-reaching implications for the rational design of vaccines aimed at the generation of protective CD8(+) T cells. C1 Penn State Univ, Milton S Hershey Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Norbury, CC (reprint author), Penn State Univ, Milton S Hershey Coll Med, Dept Microbiol & Immunol, 500 Univ Dr H107, Hershey, PA 17033 USA. EM ccn1@psu.edu RI Palmer, Douglas/B-9454-2008; Restifo, Nicholas/A-5713-2008; OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCRR NIH HHS [C06 RR-15428-01, C06 RR015428]; NIAID NIH HHS [R01 AI056094, AI056094, R56 AI056094] NR 43 TC 25 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2006 VL 119 IS 1 BP 63 EP 73 DI 10.1111/j.1365-2567.2006.02406.x PG 11 WC Immunology SC Immunology GA 072FV UT WOS:000239660200008 PM 16764686 ER PT J AU Ribot, WJ Panchal, RG Brittingham, KC Ruthel, G Kenny, TA Lane, D Curry, B Hoover, TA Friedlander, AM Bavari, S AF Ribot, Wilson J. Panchal, Rekha G. Brittingham, Katherine C. Ruthel, Gordon Kenny, Tara A. Lane, Douglas Curry, Bob Hoover, Timothy A. Friedlander, Arthur M. Bavari, Sina TI Anthrax lethal toxin impairs innate immune functions of alveolar macrophages and facilitates Bacillus anthracis survival SO INFECTION AND IMMUNITY LA English DT Article ID DENDRITIC CELLS; IN-VITRO; SPORES; SUSCEPTIBILITY; PATHOGENESIS; INFECTION; STRAIN; LINES; FATE AB Alveolar macrophages (AM) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses. Although several factors contribute to inhalational anthrax, we hypothesized that unimpeded infection of Bacillus anthracis is directly linked to disabling the innate immune functions contributed by AM. Here, we investigated the effects of lethal toxin (LT), one of the binary complex virulence factors produced by B. anthracis, on freshly isolated nonhuman primate AM. Exposure of AM to doses of LT that killed susceptible macrophages had no effect on the viability of AM, despite complete MEK1 cleavage. Intoxicated AM remained fully capable of B. anthracis spore phagocytosis. However, pretreatment of AM with LT resulted in a significant decrease in the clearance of both the Sterne strain and the fully virulent Ames strain of B. anthracis, which may have been a result of impaired AM secretion of proinflammatory cytokines. Our data imply that cytolysis does not correlate with MEK1 cleavage, and this is the first report of LT-mediated impairment of nonhuman primate AM bactericidal activity against B. anthracis. C1 USA, Med Res Inst Infect Dis, Target Identificat & Translat Res, Frederick, MD 21702 USA. SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, NCI, Frederick, MD 21702 USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Target Identificat & Translat Res, 1425 Porter St, Frederick, MD 21702 USA. EM sina.bavari@amedd.army.mil FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 27 TC 46 Z9 49 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2006 VL 74 IS 9 BP 5029 EP 5034 DI 10.1128/IAI.00275-06 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 081DC UT WOS:000240296400008 PM 16926394 ER PT J AU Lemaitre, N Sebbane, F Long, D Hinnebusch, BJ AF Lemaitre, Nadine Sebbane, Florent Long, Daniel Hinnebusch, B. Joseph TI Yersinia pestis YopJ suppresses tumor necrosis factor alpha induction and contributes to apoptosis of immune cells in the lymph node but is not required for virulence in a rat model of bubonic plague SO INFECTION AND IMMUNITY LA English DT Article ID NF-KAPPA-B; ACTIVATED PROTEIN-KINASES; DOWN-REGULATION; III SECRETION; MACROPHAGES; INFECTION; INHIBITION; PSEUDOTUBERCULOSIS; PATHOGENESIS; RESPONSES AB The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system that transfers six Yop effector proteins into host cells. One of these proteins, YopJ, has been shown to disrupt host cell signaling pathways involved in proinflammatory cytokine production and to induce macrophage apoptosis in vitro. YopJ-dependent apoptosis in mesenteric lymph nodes has also been demonstrated in a mouse model of Yersinia pseudotuberculosis infection. These results suggest that YopJ attenuates the host innate and adaptive immune response during infection, but the role of YopJ during bubonic plague has not been completely established. We evaluated the role of Yersinia pestis YopJ in a rat model of bubonic plague following intradermal infection with a fully virulent Y. pestis strain and an isogenic yopJ mutant. Deletion of yopJ resulted in a twofold decrease in the number of apoptotic immune cells in the bubo and a threefold increase in serum tumor necrosis factor alpha levels but did not result in decreased virulence, systemic spread, or colonization levels in the spleen and blood. Our results indicate that YopJ is not essential for bubonic plague pathogenesis, even after peripheral inoculation of low doses of Y. pestis. Instead, the effects of YopJ appear to overlap and augment the immunomodulatory effects of other Y. pestis virulence factors. C1 NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. INSERM, U801, F-50921 Lille, France. Univ Lille 2, Fac Med Henri Warembourg, F-59045 Lille, France. Inst Pasteur, F-59021 Lille, France. RP Hinnebusch, BJ (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov RI Sebbane, Florent/D-4213-2009 FU Intramural NIH HHS NR 33 TC 56 Z9 58 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2006 VL 74 IS 9 BP 5126 EP 5131 DI 10.1128/IAI.00219-06 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 081DC UT WOS:000240296400018 PM 16926404 ER PT J AU Lehmann, T Dalton, R Kim, EH Dahl, E Diabate, A Dabire, R Dujardin, JP AF Lehmann, Tovi Dalton, Ryan Kim, Eun Hea Dahl, Erica Diabate, Abdoulaye Dabire, Roch Dujardin, Jean Pierre TI Genetic contribution to variation in larval development time, adult size, and longevity of starved adults of Anopheles gambiae SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE anopheles; fitness; heritability; life-history traits; malaria; quantitative genetics; vectorial capacity ID PITCHER-PLANT MOSQUITO; BODY-SIZE; WYEOMYIA-SMITHII; MALARIA VECTORS; MOLECULAR-FORMS; BURKINA-FASO; DNA ANALYSIS; CULICIDAE; DIPTERA; FECUNDITY AB The variation in mosquito life-history traits such as adult size has been studied with respect to environmental factors, but the genetic contribution to such variation has received almost no consideration. Using a full-sib design of F1s produced by wild caught Anopheles gambiae (M molecular form) females, we estimated broad-sense heritability of larval developmental time, adult size (based on dry weight and wing length), and longevity of starved adults. These traits were correlated (at the phenotypic level) with each other in females and mates (vertical bar r(p)vertical bar > 0.5, P < 0.001). Longevity of starved adults increased with adult size, and both traits (adult longevity and size) decreased with longer larval development. Genetic correlations were lower (vertical bar r(g)vertical bar > 0.45, P < 0.05) but provided consistent evidence against a trade off between adult size and larval development time predicting that a mosquito can develop faster into a smaller adult or be a larger adult by a longer development. Estimates of heritability of the three traits were moderate to high (range: 0.05-0.48) and statistically significant (P < 0.05), indicating substantial genetic contribution to the phenotypic variation in these traits. These results suggest that adaptive differences are likely to be found in these traits between A. gambiae populations. (c) 2006 Elsevier B.V. All rights reserved. C1 Ctr Dis Control & Prevent, Div Parasit Dis, Entomol Branch, Chamblee, GA 30041 USA. Emory Univ, Dept Biol, Atlanta, GA 30322 USA. CNRS, Inst Rech Dev, UMR, Montpellier, France. RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2W13A, Rockville, MD 20852 USA. EM TLehmann@niaid.nih.gov FU Intramural NIH HHS NR 35 TC 37 Z9 37 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD SEP PY 2006 VL 6 IS 5 BP 410 EP 416 DI 10.1016/j.meegid.2006.01.007 PG 7 WC Infectious Diseases SC Infectious Diseases GA 068IQ UT WOS:000239367500009 PM 16524787 ER PT J AU Steinbach, WJ Walsh, TJ AF Steinbach, William J. Walsh, Thomas J. TI Mycoses in pediatric patients SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; B LIPID COMPLEX; LIPOSOMAL AMPHOTERICIN-B; CHRONIC GRANULOMATOUS-DISEASE; PULMONARY ASPERGILLOSIS; FLUCONAZOLE PROPHYLAXIS; CONTROLLED TRIAL; ORAL SOLUTION; BIRTH-WEIGHT; RISK-FACTORS AB This article provides a brief overview of some of the unique differences in invasive fungal infections in children compared with those of adults and then focuses on the key differences in antifungal pharmacology and use in children. The specific pathogens are covered in greater detail elsewhere in this issue. C1 Duke Univ, Med Ctr, Dept Pediat, Div Pediat Infect Dis, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Steinbach, WJ (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Pediat Infect Dis, Box 3499, Durham, NC 27710 USA. EM stein022@mc.duke.edu NR 75 TC 27 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 2006 VL 20 IS 3 BP 663 EP + DI 10.1016/j.idc.2006.06.006 PG 17 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 095JV UT WOS:000241304900010 PM 16984874 ER PT J AU Mansky, P Sannes, T Wallerstedt, D Ge, A Ryan, M Johnson, LL Chesney, M Gerber, L AF Mansky, Patrick Sannes, Tim Wallerstedt, Dawn Ge, Adeline Ryan, Mary Johnson, Laura Lee Chesney, Margaret Gerber, Lynn TI Tai chi chuan: Mind-body practice or exercise intervention? Studying the benefit for cancer survivors SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE Thi chi chuan; cancer survivors; quality of life; exercise; physical fitness; well-being ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; LONG-TERM SURVIVORS; BREAST-CANCER; OLDER-ADULTS; METABOLIC SYNDROME; STRESS-MANAGEMENT; CHILDHOOD-CANCER AB Tai chi chuan (TCC) has been used as a mind-body practice in Asian culture for centuries to improve wellness and reduce stress and has recently received attention by researchers as an exercise intervention. A review of the English literature on research in TCC published from 1989 to 2006 identified 20 prospective, randomized, controlled clinical trials in a number of populations, including elderly participants (7 studies), patients with cardiovascular complications (3 studies), patients with chronic disease (6 studies), and patients who might gain psychological benefit from TCC practice (2 studies). However, only the studies of TCC in the elderly and 2 studies of TCC for cardiovascular disease had adequate designs and size to allow conclusions about the efficacy of TCC. Most (11 studies) were small and provided limited information on the benefit of TCC in the settings tested. There is growing awareness that cancer survivors represent a population with multiple needs related to physical deconditioning, cardiovascular disease risk, and psychological stress. TCC as an intervention may provide benefit to cancer survivors in these multiple areas of need based on its characteristics of combining aspects of meditation and aerobic exercise. However, little research has been conducted to date to determine the benefit of TCC in this population. We propose a model to study the unique characteristics of TCC compared to physical exercise that may highlight characteristic features of this mind-body intervention in cancer survivors. C1 NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS, Bethesda, MD 20892 USA. NIH Lib, Bethesda, MD USA. George Mason Univ, Fairfax, VA 22030 USA. RP Mansky, P (reprint author), NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS, 10 Ctr Dr,CRC,Room 4-1730,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov NR 92 TC 18 Z9 20 U1 5 U2 24 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1534-7354 J9 INTEGR CANCER THER JI Integr. Cancer Ther. PD SEP PY 2006 VL 5 IS 3 BP 192 EP 201 DI 10.1177/1534735406291590 PG 10 WC Oncology; Integrative & Complementary Medicine SC Oncology; Integrative & Complementary Medicine GA 072LP UT WOS:000239675200003 PM 16880423 ER PT J AU Kolobow, T Bassi, GL Curto, F Zanella, A AF Kolobow, Theodor Bassi, Gianluigi Li Curto, Francesco Zanella, Alberto TI The Mucus Slurper: a novel tracheal tube that requires no tracheal tube suctioning. A preliminary report SO INTENSIVE CARE MEDICINE LA English DT Article DE tracheal suctioning; Mucus Slurper; Mucus Shaver; intratracheal intubation; endotracheal tube AB its internal volume. We devised the Mucus Slurper as an integral part of the tracheal tube to aspirate all mucus automatically at its distal tip. Design and setting: In vitro, and in vivo studies in sheep at the National Institutes of Health, NHLBI, PCCMB. Subjects: Six sheep, sedated, paralyzed, and mechanically ventilated Interventions: We evaluated the Mucus Slurper in vitro, and we evaluated its efficacy and safety in three healthy sheep during 24 h on volume-controlled mechanical ventilation in comparison to three sheep managed with open tracheal tube suctioning. Measurements and results: In vitro: with the Mucus Slurper connected to a source of vacuum of 450-500 mmHg the total volume of a single suction lasting 0.1, 0.2, and 0.3 s was, respectively, 75.4 +/- 7.9, 114.5 +/- 4.6, and 143.4 +/- 8.7 ml; with the measured vacuum within the lumen of the Mucus Slurper ring of 37 cmH(2)O. In vivo: during mechanical ventilation we aspirated through the Mucus Slurper 13.4 +/- 3.3 cc mucus/24 h. During the course of single aspiration the Mucus Slurper never affected the level of applied PEEP. The tracheal tube was free of tracheal secretions in the Mucus Slurper group while thin secretions were found within the ETT in the control group. Conclusion: The Mucus Slurper is a novel device designed to keep the tracheal tube and proximal trachea free of mucus. In studies in sheep lasting 24 h the Mucus Slurper was safe and prevented all mucus accumulation within the ETT. C1 NHLBI, Pulm Crit Care Med Branch, Sect Pulm & Cardiac Assist Devices, NIH, Bethesda, MD 20892 USA. RP Kolobow, T (reprint author), NHLBI, Pulm Crit Care Med Branch, Sect Pulm & Cardiac Assist Devices, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kolobowt@nhlbi.nih.gov OI zanella, Alberto/0000-0002-2967-2527 NR 7 TC 21 Z9 22 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2006 VL 32 IS 9 BP 1414 EP 1418 DI 10.1007/s00134-006-0268-5 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 113VR UT WOS:000242626600020 PM 16826389 ER PT J AU Sa-Nunes, A Rogerio, AP Medeiros, AI Fabris, VE Andreu, GP Rivera, DG Delgado, R Faccioli, LH AF Sa-Nunes, Anderson Rogerio, Alexandre P. Medeiros, Alexandra I. Fabris, Viciany E. Andreu, Gilberto P. Rivera, Dagmar G. Delgado, Ren Faccioli, Lucia H. TI Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang (R)) SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE anti-inflammatory activity; eosinophils; Toxocara canis; Mangifera indica; dexamethasone ID GUINEA-PIG MODEL; BONE-MARROW; HISTOPLASMA-CAPSULATUM; AIRWAY EOSINOPHILIA; PROTEIN-SYNTHESIS; MURINE MODEL; CELL-LINES; IN-VITRO; MICE; INFLAMMATION AB The effects of Vimang((R)), an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaccae), on cell migration in an experimental model of asthma was investigated. In vivo treatment of Toxocara canis-infected BALB/c mice for 18 days with 50 mg/kg Vimang((R)) reduced eosinophil migration into the bronchoalveolar space and peritoneal cavity. Also, eosinophil generation in bone marrow and blood eosinophilia were inhibited in infected mice treated with Vimang((R)). This reduction was associated with inhibition of IL-5 production in serum and eotaxin in lung homogenates. In all these cases the effects of Vimang((R)) were more selective than those observed with dexamethasone. Moreover, Virnang((R)) treatment is not toxic for the animals, as demonstrated by the normal body weight increase during infection. These data confirm the potent anti-inflammatory effect of Vimang R and support its potential use as an alternative therapeutic drug to the treatment of eosinophilic disorders including those caused by nematodes and allergic diseases. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, Brazil. Univ Estadual Paulista, Fac Med, BR-18618917 Botucatu, SP, Brazil. Ctr Quim Farmaceut, Dept Invest Biomed, Havana, Cuba. RP Sa-Nunes, A (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Twinbrook 3,Room 2E-28, Rockville, MD 20852 USA. EM anunes@mail.nih.gov RI Sa-Nunes, Anderson/D-8667-2012; Ivo de Medeiros, Alexandra/J-6103-2012; Lucia , Faccioli/G-8976-2015; de Paula Rogerio, Alexandre/K-8866-2013 OI Sa-Nunes, Anderson/0000-0002-1859-4973; Lucia , Faccioli/0000-0002-4999-8305; de Paula Rogerio, Alexandre/0000-0001-5913-3703 NR 54 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD SEP PY 2006 VL 6 IS 9 BP 1515 EP 1523 DI 10.1016/j.intimp.2006.04.008 PG 9 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 072LD UT WOS:000239674000016 PM 16846846 ER PT J AU Akbari, MR Malekzadeh, R Nasrollahzadeh, D Amanian, D Sun, P Islami, F Sotoudeh, M Semnani, S Boffeta, P Dawsey, SM Ghadirian, P Narod, SA AF Akbari, Mohammad Reza Malekzadeh, Reza Nasrollahzadeh, Dariush Amanian, Dayan Sun, Ping Islami, Farhad Sotoudeh, Masoud Semnani, Shahriar Boffeta, Paolo Dawsey, Sanford M. Ghadirian, Parviz Narod, Steven A. TI Familial risks of esophageal cancer among the Turkmen population of the Caspian littoral of Iran SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE esophageal cancer; hereditary; familial; genetic; Turkmen; Iran ID REPUBLIC-OF-CHINA; SHANXI-PROVINCE; GASTRIC CARDIA; LINXIAN; AGGREGATION; COHORT; TRIAL; OPIUM AB In northeastern Iran, there is an area of high incidence of esophageal cancer, which is populated by residents of Turkmen ancestry. Several environmental risk factors for esophageal cancer have been proposed, but the roles of familial and genetic factors have not been studied extensively in the Turkmen population. We evaluated the importance of familial risk factors for esophageal cancer by performing a case-control study of 167 cases of esophageal squamous cell carcinoma and 200 controls of Turkmen ethnicity. Detailed family pedigrees of the cases and controls were constructed, which documented all cancers in first- and second-degree relatives. The actuarial risk of cancer was then estimated in 2,097 first-degree relatives of cases and 2,783 first-degree relatives of the controls. A hazard ratio was constructed, based on a comparison of the 2 cumulative incidence curves. The risk to age 75 of esophageal cancer in the first-degree relatives of Turkmen patients with esophageal cancer was 34% versus 14% for the first-degree relatives of the controls (hazard ratio = 2.3; p = 3 x 10(-8)). Cases (9.6%) reported that their parents were related, versus 2.5% of the controls who reported this. (odds ratio = 4.1; p value = 0.006). Familial factors are important in the etiology of esophageal cancer among the Turkmen residents of Iran. The hazard ratio of 2.3 for cancer among first-degree relatives is consistent with an important contribution of heritable factors. It will be of interest to perform marker studies to establish which genes are responsible. (c) 2006 Wiley-Liss, Inc. C1 Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON, Canada. Univ Toronto, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. Golestan Univ Med Sci, Dept Internal Med, Gorgan, Iran. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada. RP Malekzadeh, R (reprint author), Univ Toronto, Ctr Res Womens Hlth, 7th Floor,790 Bay St, Toronto, ON M5G 1N8, Canada. EM malek@ams.ac.ir; steven.narod@sw.ca RI Semnani, Shahryar/N-2270-2016; OI Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 NR 30 TC 38 Z9 40 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2006 VL 119 IS 5 BP 1047 EP 1051 DI 10.1002/ijc.21906 PG 5 WC Oncology SC Oncology GA 067FR UT WOS:000239287800010 PM 16570268 ER PT J AU van Wijngaarden, E Dosemeci, M AF van Wijngaarden, Edwin Dosemeci, Mustafa TI Brain cancer mortality and potential occupational exposure to lead: Findings from the National Longitudinal Mortality Study, 1979-1989 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lead; occupation; brain neoplasms; cohort studies ID POISSON REGRESSION-MODELS; SMELTER WORKERS; UNITED-STATES; RISK-FACTORS; NERVOUS-SYSTEM; LUNG-CANCER; NORTHEAST CHINA; BATTERY PLANTS; BONE LEAD; TUMORS AB We evaluated the association between potential occupational lead exposure and the risk of brain cancer mortality in the National Longitudinal Mortality Study (NLMS), which is a prospective census-based cohort study of mortality among the noninstitutionalized United States population (1979-1989). The present study was limited to individuals for whom occupation and industry were available (n = 317,968). Estimates of probability and intensity of lead exposure were assigned using a job-exposure matrix (JEM). Risk estimates for the impact of lead on brain cancer mortality were computed using standardized mortality ratio (SMR) and proportional hazards and Poisson regression techniques, adjusting for the effects of age, gender and several other covariates. Brain cancer mortality rates were greater among individuals in jobs potentially involving lead exposure as compared to those unexposed (age- and gender-adjusted hazard ratio (HR) = 1.5; 95% confidence interval (CI) = 0.9-2.3) with indications of an exposure-response trend (probability: low HR = 0.7 (95% CI = 0.22.2), medium HR = 1.4 (95% CI 0.8-2.5), high HR = 2.2 (95% CI = 1.2-4.0); intensity: low HR 1.2 (95% CI = 0.7-2.1), medium/high HR = 1.9 (95% CI = 1.0-3.4)). Brain cancer risk was greatest among individuals with the highest levels of probability and intensity (HR = 2.3; 95% CI = 1.3-4.2). These findings provide further support for an association between occupational lead exposure and brain cancer mortality, but need to be interpreted cautiously due to the consideration of brain cancer as one disease entity and the absence of biological measures of lead exposure. (c) 2006 Wiley-Liss, Inc. C1 Univ Rochester, Sch Med & Dent, Dept Community & Prevent Med, Div Epidemiol, Rochester, NY 14642 USA. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP van Wijngaarden, E (reprint author), Univ Rochester, Sch Med & Dent, Dept Community & Prevent Med, Div Epidemiol, 601 Elmwood Ave,Box 644, Rochester, NY 14642 USA. EM edwin_van_wijngaarden@urmc.rochester.edu FU Intramural NIH HHS NR 90 TC 33 Z9 35 U1 7 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2006 VL 119 IS 5 BP 1136 EP 1144 DI 10.1002/ijc.21947 PG 9 WC Oncology SC Oncology GA 067FR UT WOS:000239287800022 PM 16570286 ER PT J AU Bulliard, JL Sasieni, P Klabunde, C De Landtsheer, JP Yankaskas, BC Fracheboud, J AF Bulliard, Jean-Luc Sasieni, Peter Klabunde, Carrie De Landtsheer, Jean-Pierre Yankaskas, Bonnie C. Fracheboud, Jacques TI Methodological issues in international comparison of interval breast cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE mammography; mass screening; interval cancer; international collaboration; comparative study ID MAMMOGRAPHIC SCREENING-PROGRAM; NETHERLANDS; SENSITIVITY; CENTERS; TRIALS AB International comparisons of interval cancers (IC) are important to better understand the relationship between programmes' performance and screening practices. In this respect, differences in (i) definition, (ii) identification and (iii) quantification of IC have received little attention. To examine these 3 comparability issues and activities involving IC, an assessment was conducted among member countries of the International Breast Cancer Screening Network, and the impact of accuracy of identification and quantification practices was estimated using 1996-98 data from the Dutch breast cancer screening programme. Information was obtained from 19 screening programmes in 18 countries, 16 of which acknowledged the coexistence of opportunistic screening. IC data were collected to evaluate performance of the screening programme (100% of programmes) and the radiologists (89%); 53% of programmes had a designated review process for IC. Most programmes (84%) agreed with the European Guidelines definition of IC, but a case situation exercise evidenced substantial discrepancy in classification of cancers that occurred after a positive screen. Completeness of identification of IC appears to contribute most to international variation, and cannot be easily controlled for in methodologically rigorous comparisons. Statistically significant differences of about 4% were measured between quantification methods for IC. An operational definition of IC is proposed to enhance international comparability. Valid comparisons of IC are possible with careful attention to the definition but true differences in IC frequency across screening programmes should exceed 10% to be possibly indicative of real differences between programmes. (c) 2006 Wiley-Liss, Inc. C1 Inst Univ Med Sociale & Prevent, Unite Epidemiol Canc, CH-1005 Lausanne, Switzerland. Wolfson Inst Prevent Med, London, England. NCI, Bethesda, MD 20892 USA. Breast Canc Screening Fdn, Lausanne, Switzerland. Univ N Carolina, Dept Radiol, Chapel Hill, NC 27515 USA. Univ Med Ctr, Erasmus MC, Rotterdam, Netherlands. RP Bulliard, JL (reprint author), Inst Univ Med Sociale & Prevent, Unite Epidemiol Canc, Bugnon 17, CH-1005 Lausanne, Switzerland. EM Jean-Luc.Bulliard@chuv.ch NR 32 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2006 VL 119 IS 5 BP 1158 EP 1163 DI 10.1002/ijc.21941 PG 6 WC Oncology SC Oncology GA 067FR UT WOS:000239287800025 PM 16570280 ER PT J AU Popkov, M Rader, C Gonzalez, B Sinha, SC Barbas, CF AF Popkov, Mikhail Rader, Christoph Gonzalez, Beatriz Sinha, Subhash C. Barbas, Carlos F., III TI Small molecule drug activity in melanoma models may be dramatically enhanced with an antibody effector SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE melanoma; angiogenesis; integrins; antibodies; tumor models ID ALPHA-V-INTEGRINS; TUMOR ANGIOGENESIS; BREAST-CANCER; ALPHA(V)BETA(5) INTEGRIN; ALPHA-V-BETA-3 INTEGRIN; ADAPTER IMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; MALIGNANT-MELANOMA; HUMAN SKIN; VITRONECTIN AB Monoclonal antibody (mAb) 38C2 belongs to a group of catalytic antibodies that were generated by reactive immunization and contains a reactive lysine. 38C2 catalyzes aldol and retro-aldol reactions, using an enamine mechanism, and mechanistically mimics natural aldolase enzymes. In addition, mAb 38C2 can be redirected to target integrins alpha(v)beta(3) and alpha(v)beta(5) through the formation of a covalent bond between a beta-diketone derivative of an arginine-glycine-aspartic acid (RGD) peptidomimetic and the reactive lysine residue in the antibody combining site to provide the chemically programmed mAb cp38C2. In this study, we investigated the potential of enhancing the activity of receptor-binding small molecule drug (SCS-873) through antibody conjugation. Using a M21 human melanoma xenograft model in nude mice, cp38C2 inhibited the growth of the tumor by similar to 81%. The chemically programmed antibody was shown to be highly active at a low concentration while SCS-873 alone was ineffective even at dosages similar to 1,000-fold higher than those used for the chemically programmed antibody. In vitro programming of the catalytic antibody was shown to be as effective as in vivo programming. In an experimental metastasis assay, treatment with mAb cp38C2 significantly prolonged overall survival of tumor-bearing severe combined immuno-deficient (SCID) mice when compared to treatment with unprogrammed mAb 38C2, SCS-873 alone or the integrin-specific monoclonal antibody LM609. In vitro, cp38C2 inhibited human and mouse endothelial and human melanoma cell adhesion, migration and invasion. Additionally, cp38C2 inhibited human and mouse endothelial cell proliferation and was active in complement-dependent cytotoxicity assays. These studies establish the potential of chemically programmed monoclonal antibodies as a novel and effective class of immunotherapeutics that combine the merits of traditional small molecule drug design with immunotherapy. (c) 2006 Wiley-Liss, Inc. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Barbas, CF (reprint author), Scripps Res Inst, Dept Mol Biol, BCC-550,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM carlos@scripps.edu RI Gonzalez, Beatriz /G-5158-2011 FU NCI NIH HHS [R01-CA104045] NR 48 TC 28 Z9 28 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 2006 VL 119 IS 5 BP 1194 EP 1207 DI 10.1002/ijc.21924 PG 14 WC Oncology SC Oncology GA 067FR UT WOS:000239287800029 PM 16570283 ER PT J AU Shroff, H Reba, L Thornton, LM Tozzi, F Klump, KL Berrettini, WH Brandt, H Crawford, S Crow, S Fichter, MM Goldman, D Halmi, KA Johnson, C Kaplan, AS Keel, P Lavia, M Mitchell, J Rotondo, A Strober, M Treasure, J Woodside, DB Kaye, WH Bulik, CM AF Shroff, Hernal Reba, Lauren Thornton, Laura M. Tozzi, Federica Klump, Kelly L. Berrettini, Wade H. Brandt, Harry Crawford, Steven Crow, Scott Fichter, Manfred M. Goldman, David Halmi, Katherine A. Johnson, Craig Kaplan, Allan S. Keel, Pamela LaVia, Maria Mitchell, James Rotondo, Alessandro Strober, Michael Treasure, Janet Woodside, D. Blake Kaye, Walter H. Bulik, Cynthia M. TI Features associated with excessive exercise in women with eating disorders SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE anorexia nervosa; activity; exercise; anxiety ID ANOREXIA-NERVOSA; PHYSICAL-ACTIVITY; BULIMIA-NERVOSA; SAMPLE DESCRIPTION; LONGITUDINAL DATA; ADOLESCENTS; RECOVERY; ANXIETY; MODELS; SCALE AB Objective: Excessive exercise and motor restlessness are observed in a substantial number of patients with eating disorders. This trait has been studied extensively among animal models of activity anorexia nervosa (AN) and may hold particular interest as an endophenotype for AN. We explored features associated with excessive exercise across subtypes of eating disorders. Method: Participants were female pro-bands and affected female relatives from the multi-site international Price Foundation Genetic Studies with diagnoses of AN, bulimia nervosa (BN), and both AN and BN or eating disorder not otherwise specified (ED-NOS) (N = 1,857). Excessive exercise was defined based on responses to the Structured Interview for Anorexic and Bulimic Disorders (SIAB). Results: Among the eating disorder diagnostic groups, excessive exercise was most common among the purging subtype of AN. individuals who reported excessive exercise also reported lower minimum BMI, younger age at interview, higher scores on anxiety, perfectionism, and eating disorder symptom measures, more obsessions and compulsions, and greater persistence. Conclusion: Excessive exercise may be associated particularly with the purging subtype of AN as well as with a constellation of anxious/obsessional temperament and personality characteristics among women with eating disorders. (c) 2006 by Wiley Periodicals, Inc. C1 Univ N Carolina, Dept Psychiat, Neurosci Hosp, Chapel Hill, NC 27599 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Michigan State Univ, Dept Psychol, E Lansing, MI USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Sheppard & Enoch Pratt Hosp, Ctr Eating Disorders, Towson, MD USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. Univ Munich, Roseneck Hosp Behav Med, Prien Am Chiemsee, Germany. NIAAA, Rockville, MD 20852 USA. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Westchester Div, White Plains, NY 10605 USA. Laureate Psychiat Clin & Hosp, Tulsa, OK USA. Toronto Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Univ Iowa, Dept Psychol, Ames, IA USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ Pisa, Dept Psychiat Pharmacol & Biotechnol, Pisa, Italy. Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Los Angeles, CA USA. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Bulik, CM (reprint author), Univ N Carolina, Dept Psychiat, Neurosci Hosp, 1st Floor,101 Manning Dr,CB 7160, Chapel Hill, NC 27599 USA. EM cbulik@med.unc.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Tozzi, Federica/0000-0002-3536-2920; Treasure, Janet/0000-0003-0871-4596 FU NIMH NIH HHS [MH66117] NR 38 TC 117 Z9 122 U1 4 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2006 VL 39 IS 6 BP 454 EP 461 DI 10.1002/eat.20247 PG 8 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 074HE UT WOS:000239802500003 PM 16637047 ER PT J AU Braga-Basaria, M Muller, DC Carducci, MA Dobs, AS Basaria, S AF Braga-Basaria, M. Muller, D. C. Carducci, M. A. Dobs, A. S. Basaria, S. TI Lipoprotein profile in men with prostate cancer undergoing androgen deprivation therapy SO INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH LA English DT Article DE androgen deprivation therapy; hypogonadism; hyperlipidemia; cardiovascular disease ID ARTERIAL STIFFNESS; BODY-COMPOSITION; TESTOSTERONE; DISEASE; DEATH AB Sex steroids are known to modulate serum lipoproteins. Studies have suggested that serum testosterone levels are associated with a beneficial lipid profile. Androgen deprivation therapy (ADT) is employed in the treatment of recurrent and metastatic prostate cancer (PCa), resulting in profound hypogonadism. As male hypogonadism unfavorably influences lipid profile and men with PCa have high cardiovascular mortality, we evaluated the effects of long-term ADT on fasting lipids. This Cross-sectional study was conducted in a university-based research institution. We evaluated 44 men, 16 undergoing ADT for at least 12 months before the study (ADT group), 14 age-matched eugonadal men with non-metastatic PCa who were status post prostatectomy and/or radiotherapy and not on ADT (non-ADT group) and 14 age-matched eugonadal controls (Control group). None of the men had known history of diabetes or dyslipidemia. Mean age was similar in the three groups (P = 0.37). Serum total (P < 0.01) and free (P < 0.01) testosterone levels were lower in the ADT group compared to the other groups. Men on ADT had higher body mass index (BMI) compared to the other groups (P < 0.01). Men in the ADT group had significantly higher levels of total cholesterol compared to the other two groups (P = 0.03). After adjustment for BMI, men on ADT continued to have significantly higher fasting levels of total cholesterol (P = 0.02), LDL cholesterol (P = 0.04) and non-HDL cholesterol (P = 0.03) compared to the control group. No significant differences were seen in the levels of other lipoproteins between the three groups. These data show that men undergoing long-term ADT have higher total and LDL cholesterol than age-matched controls. Long-term prospective studies are needed to determine the time of onset of changes in these lipoproteins while on ADT and the influence of these changes on cardiovascular mortality. C1 Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Med,Div Endocrinol & Metab, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Kimmel Canc Ctr, Dept Urol,Prostate Canc Res Program, Baltimore, MD USA. RP Basaria, S (reprint author), Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Dept Med,Div Endocrinol & Metab, 4940 Eastern Ave,Suite B-114, Baltimore, MD 21224 USA. EM sbasari1@jhmi.edu NR 15 TC 47 Z9 48 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0955-9930 J9 INT J IMPOT RES JI Int. J. Impot. Res. PD SEP PY 2006 VL 18 IS 5 BP 494 EP 498 DI 10.1038/sj.ijir.3901471 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 083LX UT WOS:000240458500014 PM 16617314 ER PT J AU Truesdale, KP Stevens, J Lewis, CE Schreiner, PJ Loria, CM Cai, J AF Truesdale, K. P. Stevens, J. Lewis, C. E. Schreiner, P. J. Loria, C. M. Cai, J. TI Changes in risk factors for cardiovascular disease by baseline weight status in young adults who maintain or gain weight over 15 years: the CARDIA study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body weight changes; glucose; blood pressure; cholesterol; triglycerides ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN-CHOLESTEROL; BLOOD-PRESSURE; BODY-WEIGHT; OBESITY; MEN; OVERWEIGHT; WOMEN; LIFE; US AB Objectives: To examine whether changes in cardiovascular disease (CVD) risk factors differ by baseline weight status among young adults who maintained or gained weight. Design: Longitudinal cohort study. Subjects: White and African Americans who either maintained (+/- 5 pounds; n = 488) or gained (> 5 pounds; n = 2788) weight over 15 years. Measurements: Anthropometrics and CVD risk factors were measured at baseline (1985-1986) and follow-up. Participants were classified as normal weight (body mass index (BMI) 18.5-24.9 kg/m(2)) or overweight (BMI >= 25 kg/m(2)) at baseline. Multivariable models were stratified by ethnicity and weight change category. Results: Normal weight maintainers tended to have more favorable risk factors at baseline and follow-up than overweight maintainers. Size and direction of 15-year changes in risk factors were similar by weight status, except that in white normal weight maintainers changes in high-density lipoprotein (HDL)-cholesterol (3.3 mg/dl (95% confidence interval (CI): 0.4, 6.3)) and triglycerides (-14.7 mg/dl (-25.8,-3.7)) were more favorable. Weight gain was associated with unfavorable changes in risk factors. Weight gainers normal weight at baseline had less adverse changes in glucose, blood pressure, HDL-cholesterol (whites only) and triglycerides (African Americans only) than overweight gainers. However, normal weight African-American weight gainers had more adverse changes in total (3.1 mg/dl (0.2, 6.1)) and low-density lipoprotein-cholesterol (3.4 mg/dl (0.6, 6.3)). Conclusions: Baseline weight status does not appear to influence the size or direction of risk factor changes among adults who maintained their weight over 15 years. In contrast, weight gain was associated with changes in some risk factors differentially by baseline weight status. C1 Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Epidemiol, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Epidemiol, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Truesdale, KP (reprint author), Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, 208 N Columbia St,CB 7456, Chapel Hill, NC 27599 USA. EM Kim_Truesdale@unc.edu FU NHLBI NIH HHS [N01 HC048050, N01 HC048047, N01 HC048049, N01 HC095095, N01 HC048048]; NIDDK NIH HHS [F32 DK061831-02, F32 DK061831] NR 39 TC 67 Z9 69 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 2006 VL 30 IS 9 BP 1397 EP 1407 DI 10.1038/sj.ijo.0803307 PG 11 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 077WU UT WOS:000240063200012 PM 16534519 ER PT J AU Acharya, MR Karp, JE Sausville, EA Hwang, K Ryan, Q Gojo, I Venitz, J Figg, WD Sparreboom, A AF Acharya, MR Karp, JE Sausville, EA Hwang, K Ryan, Q Gojo, I Venitz, J Figg, WD Sparreboom, A TI Factors affecting the pharmacokinetic profile of MS-275, a novel histone deacetylase inhibitor, in patients with cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE MS-275; histone deacetylation; pharmacokinetics; dosing strategy ID BODY-SURFACE AREA; VIVO ANTITUMOR-ACTIVITY; ANTICANCER AGENTS; DOSE CALCULATION; IN-VITRO; ADULTS; MASS; METABOLISM; WEIGHT; TUMORS AB Aims: To evaluate elimination pathways of the histone deacetylase inhibitor MS-275 in vitro and screen for relationships between demographic factors that may affect its pharmacokinetics in vivo. Patients and Methods: Substrate specificity of MS-275 for the liver-specific organic anion transporting polypeptides (OATPs) was assessed using Xenopus laevis oocytes, and in vitro metabolism was evaluated using human liver microsomes. In vivo pharmacokinetic data were obtained from 64 adult patients (36 male/28 female; median age, 57 years) receiving MS-275 orally (dose range, 2 to 12 mg/m(2)). Results: Accumulation of [G-H-3]MS-275 by oocytes expressing OATP1B1 or OATP1B3 was not significantly different from water-injected controls (p = 0.82). Furthermore, no metabolites could be detected after incubation of MS-275 in human liver microsomes, suggesting that hepatic metabolism is a minor pathway of elimination. The mean (+/- SD) apparent oral clearance of MS-275 was 38.5 +/- 18.7 L/h, with a coefficient of variation (%CV) of 48.7%. When clearance was adjusted for body-surface area (BSA), the inter-individual variability was similar (%CV = 50.1%). In addition, in a linear-regression analysis, except for adjusted ideal body weight (p = 0.02, |r| = 0.29), none of the studied measures (BSA, lean-body mass, ideal body weight, body-mass index, height, weight, age, and sex) was a significant covariate (p > 0.13; |r| < 0.11) for oral clearance. Conclusions: The current analysis has eliminated a number of candidate covariates from further consideration as important determinants of MS-275 absorption and disposition. Furthermore, MS-275 can be added to the list of cancer drugs where BSA-based dosing is not more accurate than fixed dosing. C1 NCI, Clin Pharmacol Res Ctr, Bethesda, MD 20892 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Ctr, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 33 TC 17 Z9 19 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD SEP PY 2006 VL 24 IS 5 BP 367 EP 375 DI 10.1007/s10637-005-5707-6 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 051HC UT WOS:000238151200001 PM 16583304 ER PT J AU Knowling, M Blackstein, M Tozer, R Bramwell, V Dancey, J Dore, N Matthews, S Eisenhauer, E AF Knowling, M Blackstein, M Tozer, R Bramwell, V Dancey, J Dore, N Matthews, S Eisenhauer, E TI A phase II study of perifosine (D-21226) in patients with previously untreated metastatic or locally advanced soft tissue sarcoma: A National Cancer Institute of Canada Clinical Trials Group trial SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE acetylphospholipid; advanced soft tissue sarcoma; perifosine; phase II; protein kinase C; MAP kinase; SAPK/JNK pathway; Akt ID GASTROINTESTINAL STROMAL TUMORS; DERMATOFIBROSARCOMA PROTUBERANS; IMATINIB MESYLATE; SOLID TUMORS; PATHWAY; TARGET AB Background/Patients and methods: 16 adult patients with untreated measurable locally advanced or metastatic inoperable soft tissue sarcoma were treated with oral perifosine, a synthetic alkylphospholipid, believed to inhibit MAP kinase (MAP-K), protein kinase C (PKC), Akt and other regulatory proteins. Perifosine was administered orally in cycles for 21 days out of 28. Loading doses were given day 1 each cycle (900 mg cycle 1, 300 mg cycle 2+) and 150 mg daily was given days 2-21 of each cycle. Cycles were repeated until disease progression, unacceptable toxicity or patient refusal. Results: Seventeen patients were enrolled; 16 and 15 were evaluable for toxicity and response, respectively. A total of 30 cycles of perifosine were administered. Most toxic effects were grade 1 or 2 and commonly included nausea, vomiting, diarrhea, and fatigue (>= 40%). Hematologic toxicity was generally mild. There were no significant biochemical abnormalities due to the drug reported. There were 4 serious adverse events (SAE)-none of which was related to perifosine. No objective responses were seen; 4 patients had stable disease for 1.3 to 8.2 months and the remainder of the patients had progressive disease.Conclusions: Perifosine when given according to this dosing schedule does not show evidence of activity in a mixed population of adult soft tissue sarcoma patients. C1 British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Tom Baker Canc Clin, Calgary, AB, Canada. NCI, CTEP, US, Bethesda, MD 20892 USA. NCIC Clin Trials Grp, Kingston, ON, Canada. RP Knowling, M (reprint author), British Columbia Canc Agcy, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM mknowling@bccancer.bc.ca NR 21 TC 52 Z9 54 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD SEP PY 2006 VL 24 IS 5 BP 435 EP 439 DI 10.1007/s10637-006-6406-7 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 051HC UT WOS:000238151200009 PM 16528479 ER PT J AU Adachi, W Ulanovsky, H Li, Y Norman, B Davis, J Piatigorsky, J AF Adachi, Wakako Ulanovsky, Hagit Li, Yan Norman, Barbara Davis, Janine Piatigorsky, Joram TI Serial analysis of gene expression (SAGE) in the rat limbal and central corneal epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OCULAR SURFACE EPITHELIA; HEPATOCYTE GROWTH-FACTOR; EPIDERMAL STEM-CELLS; HAIR FOLLICLE BULGE; ALDEHYDE DEHYDROGENASE; MURINE CORNEAL; MOUSE CORNEA; K12 KERATIN; DIFFERENTIATION; CANCER AB PURPOSE. To identify genes preferentially expressed in the stem-cell-rich limbal epithelium of the rat cornea. METHODS. The limbal and central corneal epithelial cells of 6-week-old rats were isolated by microdissection. Serial analysis of gene expression ( SAGE) libraries were constructed and analyzed, and in situ hybridization, reverse transcription-polymerase chain reaction ( RT-PCR) and cDNA cloning were conducted by conventional procedures. RESULTS. The rat limbal and central corneal epithelial SAGE libraries consisted of 41,894 and 40,691 tags, respectively. After annotation, this was reduced to 759 transcripts specific for the limbal library and 844 transcripts specific for the central corneal library; 2292 transcripts overlapped. Transcripts encoding proteins with metabolic functions comprised the major functional category in both libraries. In situ hybridization and/or RT-PCR results of 12 of the most abundant, highly enriched transcripts in the limbal epithelium were in general agreement with the SAGE data and showed that these proteins are also expressed in the conjunctival epithelium. Interesting limbal-enriched transcripts encode WDNM1-like protein ( similar to WDNM1/Expi, a putative secreted proteinase and inhibitor of metastasis), mesothelin ( a cancer marker), marapsin ( a trypsin-like serine protease that may control cell growth and migration), K4 and K15 ( both cytokeratins), and membrane-spanning four-domain subfamily A member 8B. WDNM1-like protein was cloned and confirmed as a member of the four-disulfide core family. CONCLUSIONS. The SAGE results extend the database of genes expressed in the rodent cornea and suggest an association between several genes preferentially expressed in the limbal epithelium with cellular proliferation and migration. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Haifa, Inst Evolut, Int Grad Ctr Evolut, IL-31999 Haifa, Israel. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, 7 Mem Dr,Bldg 7,Room 100, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov FU Intramural NIH HHS NR 99 TC 20 Z9 20 U1 4 U2 10 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2006 VL 47 IS 9 BP 3801 EP 3810 DI 10.1167/iovs.06-0216 PG 10 WC Ophthalmology SC Ophthalmology GA 077SP UT WOS:000240050700018 PM 16936091 ER PT J AU Oh, DJ Martin, JL Williams, AJ Russell, P Birk, DE Rhee, DJ AF Oh, Dong-Jin Martin, Jonathan L. Williams, Adrienne J. Russell, Paul Birk, David E. Rhee, Douglas J. TI Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AQUEOUS-HUMOR DYNAMICS; CYNOMOLGUS MONKEY EYES; SMOOTH-MUSCLE-CELLS; INTRAOCULAR-PRESSURE; EXTRACELLULAR-MATRIX; OCULAR HYPERTENSION; CATALYTIC DOMAIN; PROGELATINASE-A; GENE-EXPRESSION; CILIARY MUSCLE AB PURPOSE. To determine the effect of latanoprost on the expression of human matrix metalloproteinases ( MMPs) and tissue inhibitors of metalloproteinases ( TIMPs) in the trabecular meshwork ( TM). METHODS. Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS. The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 ( in four of five cultures), MMP-3 ( in four of five cultures), MMP-17 ( in three of five cultures), MMP-24 ( in all five cultures), TIMP-2, -3, and -4 expression ( in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS. Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Thomas Jefferson Univ, Wills Eye Hosp, Lab Mol Ophthalmol, Philadelphia, PA 19107 USA. NEI, Sect Aging & Ocular Dis, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com RI Birk, David/I-4072-2012 OI Birk, David/0000-0002-4865-9088 FU NEI NIH HHS [EY 13997] NR 64 TC 42 Z9 42 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2006 VL 47 IS 9 BP 3887 EP 3895 DI 10.1167/iovs.06-0036 PG 9 WC Ophthalmology SC Ophthalmology GA 077SP UT WOS:000240050700028 PM 16936101 ER PT J AU Tang, JS Choy, G Bernardo, M Thomasson, D Libutti, SK Choyke, PL AF Tang, Jin Shan Choy, Garry Bernardo, Marcelino Thomasson, David Libutti, Steven K. Choyke, Peter L. TI Dynamic contrast-enhanced magnetic resonance imaging in the assessment of early response to tumor necrosis factor alpha in a colon carcinoma model SO INVESTIGATIVE RADIOLOGY LA English DT Article DE DCE MRI; tumor; general kinetic model; angiogenic inhibitor; antivascular therapy TNF alpha; coefficients of variation ID DIFFERENT MOLECULAR-WEIGHTS; MICROVASCULAR CHANGES; CLINICAL-TRIALS; MRI; ANGIOGENESIS; AGENTS; MEDIA AB Objective: We describe the effects of tumor necrosis factor alpha (TNF alpha) on tumor microvasculature in a murine colon carcinoma model using serial dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Material and Methods: Mice with subcutaneous murine colon carcinomas (MC-38) were imaged at 4.7 T after administration of 0.2 mmol/kg gadolinium-DTPA. Both treated and control mice (each group, n = 4), were scanned at baseline and 2, 4, 6, and 96 hours. A 2-compartment pharmacokinefic model generated parameters such as tc ns, k,p, and initial area under the gadolinium concentration curve (IAUC). Results: The treatment group revealed significant differences in K-trans at all time points after TNFa. k,P and IAUC were significantly reduced at 2, 6, and 96 hours. The coefficient of variation in control animals ranged from 0.13 for IAUC to 0.30 for K-trans. Mild histologic changes were observed at 2 to 6 hours, but considerable central necrosis with a vascular tumor rim was seen at 96 hours. Conclusion: DCE MRI can be used to detect early effects of TNFa. Serial DCE MRI is a promising tool in assessing the early effects of antivascular therapies. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM pchoyke@nih.gov FU Intramural NIH HHS NR 12 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD SEP PY 2006 VL 41 IS 9 BP 691 EP 696 DI 10.1097/01.rli.0000233882.83800.fb PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 077TZ UT WOS:000240054600006 PM 16896304 ER PT J AU Brock, MV Hooker, CM Engels, EA Moore, RD Gillison, ML Alberg, AJ Keruly, JC Yang, SC Heitmiller, RF Baylin, SB Herman, JG Brahmer, JR AF Brock, Malcolm V. Hooker, Craig M. Engels, Eric A. Moore, Richard D. Gillison, Maura L. Alberg, Anthony J. Keruly, Jeanne C. Yang, Stephen C. Heitmiller, Richard F. Baylin, Stephen B. Herman, James G. Brahmer, Julie R. TI Delayed diagnosis and elevated mortality in an urban population with HIV and lung cancer: Implications for patient care SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE lung cancers; surveillance; mortality; survival; AIDS; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; BRONCHOGENIC-CARCINOMA; INFECTED PATIENTS; CHEST RADIOGRAPHS; POSITIVE PATIENTS; KAPOSIS SARCOMA; CT SCANS; AIDS; ERA AB Objective: Lung cancer is more common in HIV-infected patients than in the general population. We examined how effectively lung cancer was being diagnosed in our HIV-infected patients. Methods: Retrospective study assessing clinical diagnosis of lung cancer in HIV-infected patients at Johns Hopkins Hospital between 1986 and 2004. Results: Ninety-two patients were identified. Compared to HIV-indeterminate patients (n = 4973), HIV-infected individuals were younger with more advanced cancer. CD4 counts and HIV-1 RNA levels indicated preserved immune function. Mortality was higher in HIV-infected patients, with 92% dying of lung cancer (hazard ratio, 1.57; 95% confidence interval, 1.25-1.96), compared to HIV-uninfected patients. Advanced stage and black race were associated with worse survival. After adjustment for these factors, HIV infection was not associated with increased mortality (hazard ratio, 1.04; 95% confidence interval, 0.83-1.32). Of 32 patients followed in our HIV clinic, 60% of chest radiographs had no evidence of neoplasm within 1 year of diagnosis compared to only 1 (4%) of 28 chest computed tomography scans. Nonspecific infiltrates were observed in 9 patients in the same area that cancer was subsequently diagnosed. Conclusions: HIV-infected lung cancer patients have shortened survival mainly due to advanced stage. Low clinical suspicion and overreliance on chest radiographs hindered earlier detection. Aggressive follow-up of nonspecific pulmonary infiltrates in these patients is warranted. C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Union Mem Hosp, Baltimore, MD USA. RP Brock, MV (reprint author), Johns Hopkins Med Inst, 600 N Wolfe,Blalock 240, Baltimore, MD 21287 USA. EM mabrock@jhmi.edu FU Intramural NIH HHS; NCI NIH HHS [CA058184-10, 5U01CA086308, CA117820-01]; NIAID NIH HHS [P30-AI42855] NR 34 TC 67 Z9 68 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP PY 2006 VL 43 IS 1 BP 47 EP 55 DI 10.1097/01.qai.0000232260.95288.93 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 080YK UT WOS:000240284200008 PM 16936558 ER PT J AU Sateren, WB Foglia, G Renzullo, PO Elson, L Wasunna, M Bautista, CT Birx, DL AF Sateren, Warren B. Foglia, Ginamarie Renzullo, Philip O. Elson, Lynne Wasunna, Monique Bautista, Christian T. Birx, Deborah L. TI Epidemiology of HIV-1 infection in agricultural plantation residents in Kericho, Kenya: Preparation for vaccine feasibility studies SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN SP Univ N Carolina, Gen Clin Res Ctr, UNC Ctr AIDS Res, Natl Inst Hlth, Swiss Natl AIDS Res Program, Bristol-Myers Squibb Co, Boehringer Ingelheim, GlaxoWellcome Res & Dev, HIV Antiviral Res DE HIV; prevalence; risk factors; vaccine; Kericho; Kenya ID IMMUNODEFICIENCY-VIRUS TYPE-1; MALE CIRCUMCISION; GENETIC DIVERSITY; WOMEN; AFRICA; RISK; MEN; RECOMBINANTS; METAANALYSIS; ASSOCIATION AB A cross-sectional study was performed to determine the prevalence and risk factors for HIV-1 infection among agricultural plantation residents in Kericho, Kenya. Volunteers were recruited, interviewed, and phlebotomized for HIV-1 serologic testing. Sex-specific adjusted odds ratios were estimated using logistic regression. The overall HIV-1 prevalence was 9.9% (81/820), with prevalence in women more than twice that in men (17.4% vs 8.0%, P = 0.001). Among men, elevated HIV-1 prevalence was seen with increasing age, peaking in those older than 30 years (10.3%), marriage (10.4%), Luo tribe affiliation (23.5%), employment (8.9%), travel (11.0%), and being uncircumcised (29.2%). Among women, elevated HIV-1 prevalence was seen in those with no formal education (36.8%) and those who received goods in exchange for sex (36.0%). More than 97% of volunteers expressed a willingness to participate in future HIV-1 studies requiring semiannual visits. HIV prevention efforts have been implemented, along with further research to characterize this population for future cohort feasibility studies and HIV-1 vaccine efficacy trials. C1 Walter Reed Army Inst Res, Div Retrovirol, US Mil HIV Res Program, Rockville, MD 20850 USA. Henry M Jackson Fdn Advancement Mil Med, Rockville, MD USA. USAMRUK, Nairobi, Kenya. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. US Mil, HIV Res Program, Walter Reed Project, Kericho, Kenya. Kenya Govt Med Res Ctr, Nairobi, Kenya. RP Sateren, WB (reprint author), Walter Reed Army Inst Res, Div Retrovirol, US Mil HIV Res Program, 1 Taft Court,Suite 250, Rockville, MD 20850 USA. EM wsateren@hivresearch.org RI Bautista, Christian/B-2812-2011 NR 25 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD SEP PY 2006 VL 43 IS 1 BP 102 EP 106 DI 10.1097/01.qai.0000226795.61957.40 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 080YK UT WOS:000240284200017 PM 16885773 ER PT J AU Gabler, M Scheiblhofer, S Kern, K Leitner, WW Stoecklinger, A Hauser-Kronberger, C Alinger, B Lechner, B Prinz, M Vrtala, S Valenta, R Thalhamer, J Weiss, R AF Gabler, Maximilian Scheiblhofer, Sandra Kern, Kerstin Leitner, Wolfgang W. Stoecklinger, Angelika Hauser-Kronberger, Cornelia Alinger, Beate Lechner, Berta Prinz, Monika Vrtala, Susanne Valenta, Rudolf Thalhamer, Josef Weiss, Richard TI Immunization with a low-dose replicon DNA vaccine encoding Phl p 5 effectively prevents allergic sensitization SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE type I allergy; DNA vaccine; genetic immunization; replicase; alphavirus; Phl p 5; IgE; bronchoalveolar lavage; eosinophils; lung pathology ID IMMUNOGLOBULIN-E SYNTHESIS; IGE ANTIBODY-FORMATION; BIRCH-POLLEN ALLERGEN; IMMUNE-RESPONSES; DENDRITIC CELLS; TH1 RESPONSES; IN-VIVO; GENETIC IMMUNIZATION; AIRWAY INFLAMMATION; MAJOR ALLERGEN AB Background: Replicase-based DNA vaccines stimulate T(H)1-biased immune responses at ultralow doses and induce self-removal of transfected cells through apoptosis. Both aspects are important requirements for efficient and safe DNA-based immunotherapy of type I allergies. Objective: A Sindbis virus replicon-based DNA vaccine encoding the major timothy grass pollen allergen Phi p 5 was evaluated for its antiallergic potential compared with a conventional DNA vaccine in a BALB/c mouse model of allergy. Methods: Mice were intradermally prevaccinated with plasmid DNA, followed by sensitization and intranasal allergen provocation with recombinant Phi p 5. In vitro proliferation and cytokine secretion was measured in splenocyte cultures. Distribution of IgG1, IgG2a, and IgE antibody subclasses was determined by means of ELISA. IgE-mediated degranulation was measured with the basophil release assay. Bronchoalveolar lavage fluid was analyzed for eosinophils, IL-4, IL-5, IL-13, and IFN-gamma. Mucus production, inflammatory infiltrates, and epithelial damage were determined in lung sections. Results: Both vaccines induced T(H)1-biased immune responses, resulting in suppression of functional IgE, reduction of eosinophilia in bronchoalveolar lavage fluid, and alleviation of lung pathology. However, immunization with the replicon DNA vaccine elicited these effects at a 100-fold lower dose compared with the conventional DNA vaccine. Conclusions: The increased immunogenicity of replicon-based DNA vaccines allows for application of extremely low doses, thereby eliminating the concerns associated with conventional DNA vaccines, which have to be administered at milligram amounts to induce immune reactions in human subjects. Clinical implications: Their high safety profile makes replicon-based DNA vaccines promising candidates for treatment of type I allergies in the clinic. C1 Salzburg Univ, Dept Mol Biol, Div Allergy & Immunol, Christian Doppler Lab Allergy Diagnost & Therapy, A-5020 Salzburg, Austria. Natl Canc Inst, Dermatol Branch, NIH, Bethesda, MD USA. Gen Hosp & Paracelsus Univ Salzburg, Dept Pathol, Salzburg, Austria. Med Univ Vienna, Dept Pathophysiol, Ctr Physiol & Pathophysiol, Vienna, Austria. RP Thalhamer, J (reprint author), Salzburg Univ, Dept Mol Biol, Div Allergy & Immunol, Christian Doppler Lab Allergy Diagnost & Therapy, Hellbrunnerstasse 34, A-5020 Salzburg, Austria. EM Josef.Thalhamer@sbg.ac.at RI Leitner, Wolfgang/F-5741-2011; Weiss, Richard/N-7279-2013; Thalhamer, Josef/E-5787-2011 OI Leitner, Wolfgang/0000-0003-3125-5922; Weiss, Richard/0000-0003-3185-7253; Thalhamer, Josef/0000-0003-2285-6400 FU Austrian Science Fund FWF [L 181] NR 48 TC 26 Z9 30 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2006 VL 118 IS 3 BP 734 EP 741 DI 10.1016/j.jaci.2006.04.048 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 086BV UT WOS:000240649000031 PM 16950295 ER PT J AU Launso, L Drageset, BJ Fonnebo, V Jacobson, JS Haahr, N White, JD Salamonsen, A Horneber, M Egeland, E AF Launso, Laila Drageset, Brit J. Fonnebo, Vinjar Jacobson, Judith S. Haahr, Niels White, Jeffrey D. Salamonsen, Anita Horneber, Markus Egeland, Else TI Exceptional disease courses after the use of CAM: Selection, registration, medical assessment, and research. An international perspective SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ALTERNATIVE MEDICINE; UNITED-STATES; THERAPIES; ACUPUNCTURE; PATTERNS; CANCER AB Objectives: To describe the different approaches that investigators in several countries have used to obtain, register, assess, and research exceptional case histories after the use of complementary and alternative medicine (CAM). Methods: Searches have been carried out currently in the databases PubMed and MEDLINE(R) using the keywords: exceptional disease course/best and worst cases/best-case series + use of CAM. We have only found a few papers limited to best-case series and cancer. Furthermore, we have used the "snowball method" by contacting researchers in different countries starting with with the National Cancer Institute in the United States in order to get information about ongoing approaches to obtain, register, assess, and research exceptional case histories after the use of CAM. Results: There appears to be a gap between "evidence-based" knowledge drawn from randomized controlled trials, systematic reviews, and meta-analyses and experience-based knowledge of treatment outcomes reported by patients and CAM providers. Several research groups in different countries have initiated studies on patients experiencing exceptional treatment outcomes after the use of CAM. Four different approaches to collecting and assessing such case histories have been identified. Three of the approaches collect histories from the treatment providers, whereas the fourth recruits case histories mainly from patients themselves. The medical assessments are generally similar, and seek to document whether the course of disease is different than would have been expected in a conventional treatment situation. Conclusions: Given differences in the current procedures, the establishment of an international formal collaboration for the recruitment, assessment, and study of exceptional patients is likely to take time. Comparative studies may, however, generate new knowledge about exceptional disease courses across disease categories, cultural contexts, and national boundaries. Our recommendations are that therapeutic approaches that show promising results should warrant prospective study and randomized clinical trials. In addition we recommend that there be (1) agreement on the definition of an exceptional patient, (2) agreement on the interpretation of treatment results, (3) agreement on content requirements of medical records, (4) more consideration of worst cases, (5) more international exchange of experience with registration procedures, and (6) more international exchange of experience with medical assessment procedures. C1 Univ Tromso, NAFKAM, N-9037 Tromso, Norway. Columbia Univ, New York, NY USA. Danish Multiple Sclerosis Soc, Copenhagen, Denmark. NCI, Off Canc Complimentary & Alternat Med, NIH, Bethesda, MD 20892 USA. Klinikum Nuernberg, Dept Internal Med Oncol & Hematol, Nurnberg, Germany. RP Drageset, BJ (reprint author), Univ Tromso, NAFKAM, N-9037 Tromso, Norway. EM brit.drageset@fagmed.uit.no NR 22 TC 12 Z9 12 U1 2 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2006 VL 12 IS 7 BP 607 EP 613 DI 10.1089/acm.2006.12.607 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 085MK UT WOS:000240608000004 PM 16970530 ER PT J AU Tweedie, D Brossi, A Chen, DM Ge, YW Bailey, J Yu, QS Kamal, MA Sambamurti, K Lahiri, DK Greig, NH AF Tweedie, David Brossi, Arnold Chen, DeMoa Ge, Yuan-Wen Bailey, Jason Yu, Qian-sheng Kamal, Mohammad A. Sambamurti, Kumar Lahiri, Debomoy K. Greig, Nigel H. TI Neurine, an acetylcholine autolysis product, elevates secreted amyloid-beta protein precursor and amyloid-beta peptide levels, and lowers neuronal cell viability in culture: A role in Alzheimer's disease? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; neurine; amyloid-beta protein precursor; amyloid-beta peptide; acetylcholine; ptomaine ID CENTRAL CHOLINERGIC NEURONS; LONG-TERM POTENTIATION; OXIDATIVE STRESS; CORTICAL-NEURONS; OLIGOMERS; TARGETS; TOXICITY AB Classical hallmarks of Alzheimer's disease (AD) are a synaptic loss, cholinergic neuron death, and abnormal protein deposition, particularly of toxic amyloid-beta peptide (A beta) that is derived from amyloid-beta protein precursor (AOPP) by the action of beta- and gamma-secretases. The trigger(s) initiating the biochemical cascades that underpin these hallmarks have yet to be fully elucidated. The typical forebrain cholinergic cell demise associated with AD brain results in a loss of presynaptic cholinergic markers and acetylcholine (ACh). Neurine (vinyl-trimethyl-ammonium hydroxide) is a breakdown product of ACh, consequent to autolysis and is an organic poison found in cadavre brain. The time- and concentration-dependent actions of neurine were assessed in human neuroblastoma (NB, SK-N-SH) cells in culture by quantifying cell viability by lactate dehydrogenase (LDH) and MTS assay, and A beta PP and A beta levels by Western blot and ELISA. NB cells displayed evidence of toxicity to neurine at >= 3 mg/ml, as demonstrated by elevated LDH levels in the culture media and a reduced cell viability shown by the MTS assay. Using subtoxic concentrations of neurine, elevations in A beta PP and A beta 1-40 peptide levels were detected in conditioned media samples. C1 NIA, Drug Design & Dev Sect, Gerontol Res Ctr, Neurosci Lab,Intramural Res Program, Baltimore, MD 21224 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. Enzymoics, Habersham, NSW 2770, Australia. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29464 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Gerontol Res Ctr, Neurosci Lab,Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Greign@grc.nia.nih.gov RI Kamal, Mohammad/H-9643-2012; OI Kamal, Mohammad/0000-0003-1862-173X; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU Intramural NIH HHS; NIA NIH HHS [R01AG023055] NR 38 TC 4 Z9 5 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD SEP PY 2006 VL 10 IS 1 BP 9 EP 16 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 107FC UT WOS:000242155100002 PM 16988475 ER PT J AU Savory, J Herman, MM Ghribi, O AF Savory, John Herman, Mary M. Ghribi, Othman TI Supplementation of the diet with silicic acid to reduce body burden of aluminum: A miracle cure or useless treatment for Alzheimer's disease? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Editorial Material ID DEMENTIA; WATER C1 Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22903 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. Univ N Dakota, Sch Med, Dept Pharamcol Physiol & Therapeut, Grand Forks, ND 58201 USA. RP Savory, J (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Pathol, POB 800214, Charlottesville, VA 22903 USA. EM js2r@virginia.edu NR 13 TC 1 Z9 1 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD SEP PY 2006 VL 10 IS 1 BP 25 EP 27 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 107FC UT WOS:000242155100004 PM 16988477 ER PT J AU Kamal, MA Klein, P Yu, QS Tweedie, D Li, YZ Holloway, HW Greig, NH AF Kamal, Mohammad A. Klein, Peter Yu, Qian-sheng Tweedie, David Li, Yazhou Holloway, Harold W. Greig, Nigel H. TI Kinetics of human serum butyrylcholinesterase and its inhibition by a novel experimental Alzheimer therapeutic, bisnorcymserine SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; bisnorcymserine; butyrylcholinesterase; acetylcholinesterase; anticholinesterases; enzyme kinetics; phenserine; physostigmine; cholinergic ID ACETYLCHOLINESTERASE INHIBITION; CHOLINESTERASE-INHIBITORS; SENILE DEMENTIA; DISEASE; PHENSERINE; PLAQUES; PROTEIN; ROLES AB An explosion in the incidence of neurodegenerative diseases, particularly Alzheimer's disease (AD), is predicted in coming decades. Hence, the need to devise and assess new treatment strategies has never been more acute. AD, although an irreversible and progressive disorder, is currently treated with palliative, symptomatic therapy: primarily with acetylcholinesterase (AChE) inhibitors to amplify remaining cholinergic activity. New agents that, additionally, affect disease progression are sorely needed. Inhibition of brain butyrylcholinesterase (BuChE) represents a new drug target for AD treatment. Therefore, hand-in-hand with the development of selective ligands to inhibit BuChE in brain, it is fundamental to optimize assay conditions for kinetic studies of human BuChE. Kinetic analysis of serum BuChE, which is structurally similar to brain enzyme, was performed at dual substrate (butyrylthiocholine iodide) concentration ranges: 3-80 mu M (low) and 25-800 mu M (optimal) by use of the Ellman technique. Interaction of BuChE with a novel experimental AD therapeutic, bisnorcymserine (BNC; 0.06-2.0 nM) was also studied ex vivo. The IC50 and other key kinetic constants were determined for human serum BuChE inhibition by BNC, which proved to be a highly potent inhibitor in comparison to its structural analogue, cymserine. BNC may, additionally, lower the amyloid plaque-associated protein, amyloid-beta peptide. In synopsis, the characterization of the kinetic parameters of BuChE and BNC, described herein, is both aiding in the design of novel agents and optimizing their translation toward clinical use. C1 NIA, Drug Design & Dev Sect, Gerontol Res Ctr, Lab Neurosci,Intramural Res Program,NIH, Baltimore, MD 21224 USA. TAFE, Ultimo, NSW 2007, Australia. Enzymoics, Hebersham, NSW 2770, Australia. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Gerontol Res Ctr, Lab Neurosci,Intramural Res Program,NIH, Room 2C13,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM makamal@optusnet.com.au; Greign@grc.nia.nih.gov RI Kamal, Mohammad/H-9643-2012; Kamal, Mohammad/J-4622-2013; OI Kamal, Mohammad/0000-0003-1862-173X; Kamal, Mohammad Amjad/0000-0003-0088-0565 FU Intramural NIH HHS NR 44 TC 26 Z9 31 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD SEP PY 2006 VL 10 IS 1 BP 43 EP 51 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 107FC UT WOS:000242155100008 PM 16988481 ER PT J AU Vong, QP Li, YM Lau, YFC Dym, M Rennert, OM Chan, WY AF Vong, Queenie P. Li, Yunmin Lau, Yun-Fai Chris Dym, Martin Rennert, Owen M. Chan, Wai-Yee TI Structural characterization and expression studies of Dby and its homologs in the mouse SO JOURNAL OF ANDROLOGY LA English DT Article DE Ddx3; D1Pas1; 3 '-UTR; gonad; spermatogonia; spermatocytes; spermatids ID HUMAN Y-CHROMOSOME; DEHYDROGENASE E1-ALPHA SUBUNIT; HUMAN AZFA REGION; INTRACHROMOSOMAL RECOMBINATION; MALE-INFERTILITY; A-SPERMATOGONIA; SERTOLI-CELLS; GENE; PROTEIN; SPERMATOGENESIS AB In spite of recent evidence showing the importance of DBY(DEAD-box RNA helicase Y) in spermatogenesis in human, the biologic role of its homolog Dby (also known as Ddx3y) in the mouse is less clear. The present study aims at characterizing the molecular structure of Dby and comparing its expression with its X- and autosome-linked homologs in embryonic gonads and developing germ cells in mice. Molecular cloning by rapid amplification of 3'-cDNA ends showed that the Dby gene in the mouse gives rise to 2 transcripts that differ only in the length of the 3'-untranslated region as a consequence of the use of alternative polyadenylation signals. Measurement by quantitative real-time polymerase chain reaction showed that both transcripts were ubiquitously expressed and were present in male germ cells and Sertoli cells. They were more abundant in type A spermatogonia compared with pachytene spermatocytes and round spermatids. Expression of Dby in the embryonic gonad increased from day 10.5 and reached a peak at day 17.5. The expression level of Dby decreased after birth and remained low in adult male gonads. Although the level of expression of Dby was much lower than its X chromosome homolog, Ddx3 (also known as Ddx3x) in all samples examined, the pattern of expression of the 2 genes was comparable. In contrast, their autosomal homolog, D1Pas1(also known as PL10), was predominantly expressed in pachytene spermatocytes and round spermatids. This result is in accord with meiotic sex chromosome inactivation in that Dby and Ddx are replaced in pachytene spermatocytes by their autosomal retroposon. These observations indicate that unlike DBY in humans, the role of Dby in spermatogenesis is less obvious in the mouse and its biologic activity may be replaced by that of Ddx3 and D1Pas1. C1 NICHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94143 USA. Georgetown Univ, Dept Cell Biol, Washington, DC USA. Georgetown Univ, Dept Pediat, Washington, DC 20057 USA. RP Chan, WY (reprint author), NICHD, Lab Clin Genom, NIH, Bldg 49,Room 2A08,49 Convent Dr,MSC 4429, Bethesda, MD 20892 USA. EM chanwy@mail.nih.gov OI Lau, Yun-Fai /0000-0002-9119-7050 FU Intramural NIH HHS; NICHD NIH HHS [HD33728, HD36483, HD38117] NR 37 TC 18 Z9 20 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD SEP-OCT PY 2006 VL 27 IS 5 BP 653 EP 661 DI 10.2164/jandrol.106.000471 PG 9 WC Andrology SC Endocrinology & Metabolism GA 085MM UT WOS:000240608200006 PM 16728723 ER PT J AU Saint-Joanis, B Demangel, C Jackson, M Brodin, P Marsollier, L Boshoff, H Cole, ST AF Saint-Joanis, Brigitte Demangel, Caroline Jackson, Mary Brodin, Priscille Marsollier, Laurent Boshoff, Helena Cole, Stewart T. TI Inactivation of Rv2525c, a substrate of the twin arginine translocation (Tat) system of Mycobacterium tuberculosis, increases beta-lactam susceptibility and virulence SO JOURNAL OF BACTERIOLOGY LA English DT Article ID INDEPENDENT PROTEIN EXPORT; PATHWAY; SECRETION; GROWTH; MUTAGENESIS; SMEGMATIS; SEQUENCE AB The twin arginine translocation (Tat) system is used by many bacteria to export fully folded proteins containing cofactors. Here, we show genetically that this system is essential for Mycobacterium tuberculosis, as the tatAC operon and tatB genes could be inactivated only in partially diploid strains. Using comparative genomics, the rv2525c gene of M. tuberculosis was identified as encoding a histidine-rich protein, with a twin arginine signal peptide, and orthologous genes were shown to be present in several but not all actinobacterial species. Conservation of this gene by Mycobacterium leprae, which has undergone reductive evolution, suggested an important role for rv2525c. An rv2525c knockout mutant was constructed, and biochemical analysis indicated that the mature Rv2525c protein is secreted. Upon exposure to antituberculous drugs, rv2525c expression is significantly up-regulated together with those of other genes involved in cell wall biogenesis. Phenotypic comparison of the mutant with the parental strain revealed an increase in susceptibility to some beta-lactam antibiotics and, despite slower growth in vitro, enhanced virulence in both cellular and murine models of tuberculosis. The Tat system thus contributes in multiple ways to survival of the tubercle bacillus. C1 Inst Pasteur, Unite Genet Mol Bacterienne, F-75724 Paris, France. Inst Pasteur, Unite Genet Mycobacterienne, F-75724 Paris, France. NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. RP Cole, ST (reprint author), Inst Pasteur, Unite Genet Mol Bacterienne, 28 Rue Dr Roux, F-75724 Paris, France. RI Demangel, Caroline/H-9570-2014; Marsollier, Laurent/P-6178-2015; Brodin, Priscille/E-5802-2014; Jackson, Mary/D-5345-2017 OI Brodin, Priscille/0000-0003-0991-7344; NR 30 TC 49 Z9 56 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2006 VL 188 IS 18 BP 6669 EP 6679 DI 10.1128/JB.00631-06 PG 11 WC Microbiology SC Microbiology GA 083RM UT WOS:000240475900026 PM 16952959 ER PT J AU Hur, GM Kim, YS Won, M Choksi, S Liu, ZG AF Hur, Gang Min Kim, You-Sun Won, Minho Choksi, Swati Liu, Zheng-Gang TI The death domain kinase RIP has an important role in DNA damage-induced, p53-independent cell death SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B ACTIVATION; RECEPTOR-INTERACTING PROTEIN; JNK ACTIVATION; P53; NECROSIS; STRESS; RESISTANCE; APOPTOSIS; RESPONSES; PATHWAY AB Tumor suppressor p53 plays a critical role in cellular responses, such as cell cycle arrest and apoptosis following DNA damage. DNA damage-induced cell death can be mediated by a p53-dependent or p53-independent pathway. Although p53-mediated apoptosis has been well documented, little is known about the signaling components of p53-independent cell death. Here we report that the death domain kinase, RIP (receptor-interacting protein), is important for DNA damage-induced, p53-independent cell death. DNA damage induces cell death in both wild-type and p53(-/-) mouse embryonic fibroblast cells. We found that RIP-/- mouse embryonic fibroblast cells, which have a mutant form of the p53 protein, are resistant to DNA damage-induced cell death. The reconstitution of RIP protein expression in RIP-/- cells restored the sensitivity of cells to DNA damage-induced cell death. We also found that RIP mediates this process through activating mitogen-activated protein kinase, JNK1. Furthermore, knocking down the expression of RIP blocked DNA damage-induced cell death in the human colon cancer cell line, p53 null HCT 116. Taken together, our study demonstrates that RIP is one of the critical components involved in mediating DNA damage-induced, p53-independent cell death. C1 NCI, Cell & Canc Biol Branch, NIH, Canc Res Ctr, Bethesda, MD 20892 USA. Chungnam Natl Univ, Dept Pharmacol, Coll Med, Taejon, South Korea. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, NIH, Canc Res Ctr, 37 Convent Dr,Rm 1066A, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov NR 27 TC 14 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25011 EP 25017 DI 10.1074/jbc.M605577200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300003 PM 16825191 ER PT J AU Helle, F Wychowski, C Vu-Dac, N Gustafson, KR Voisset, C Dubuisson, J AF Helle, Francois Wychowski, Czeslaw Vu-Dac, Ngoc Gustafson, Kirk R. Voisset, Cecile Dubuisson, Jean TI Cyanovirin-N inhibits hepatitis C virus entry by binding to envelope protein glycans SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM; INACTIVATING PROTEIN; GLYCOPROTEIN E2; PSEUDOTYPE PARTICLES; CELL-CULTURE; GP120; HIV; GLYCOSYLATION; LOCALIZATION; COMPLEXES AB Inhibition of viruses at the stage of viral entry provides a route for therapeutic intervention. Because of difficulties in propagating hepatitis C virus (HCV) in cell culture, entry inhibitors have not yet been reported for this virus. However, with the development of retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recent progress in amplification of HCV in cell culture (HCVcc), studying HCV entry is now possible. In addition, these systems are essential for the identification and the characterization of molecules that block HCV entry. The lectin cyanovirin-N (CV-N) has initially been discovered based on its potent activity against human immunodeficiency virus. Because HCV envelope glycoproteins are highly glycosylated, we sought to determine whether CV-N has an antiviral activity against this virus. CV-N inhibited the infectivity of HCVcc and HCVpp at low nanomolar concentrations. This inhibition is attributed to the interaction of CV-N with HCV envelope glycoproteins. In addition, we showed that the carbohydrate binding property of CV-N is involved in the anti-HCV activity. Finally, CV-N bound to HCV envelope glycoproteins and blocked the interaction between the envelope protein E2 and CD81, a cell surface molecule involved in HCV entry. These data demonstrate that targeting the glycans of HCV envelope proteins is a promising approach in the development of antiviral therapies to combat a virus that is a major cause of chronic liver diseases. Furthermore, CV-N is a new invaluable tool to further dissect the early steps of HCV entry into host cells. C1 Inst Pasteur, Ctr Natl Rech Sci, Inst Biol, Unite Mixt Rech 8161,Hepatitis C Lab,UMR8161, F-59021 Lille, France. NCI, Mol Targets Dev Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Dubuisson, J (reprint author), Inst Pasteur, Ctr Natl Rech Sci, Inst Biol, Unite Mixt Rech 8161,Hepatitis C Lab,UMR8161, 1 Rue Calmette,BP447, F-59021 Lille, France. EM jean.dubuisson@ibl.fr RI HELLE, Francois/G-7427-2011; OI HELLE, Francois/0000-0001-6884-2456; Dubuisson, Jean/0000-0003-1626-7693 NR 48 TC 113 Z9 120 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25177 EP 25183 DI 10.1074/jbc.M602431200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300018 PM 16809348 ER PT J AU Hu, L Wada, K Mores, N Krsmanovic, LZ Catt, KJ AF Hu, Lian Wada, Keiko Mores, Nadia Krsmanovic, Lazar Z. Catt, Kevin J. TI Essential role of G protein-gated inwardly rectifying potassium channels in gonadotropin-induced regulation of GnRH neuronal firing and pulsatile neurosecretion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; HYPOTHALAMIC NEURONS; RAT HYPOTHALAMUS; RHESUS-MONKEY; GIRK CHANNELS; 5-HYDROXYTRYPTAMINE1A RECEPTORS; PRESYNAPTIC INHIBITION; SIGNALING PATHWAYS; ADENYLYL-CYCLASE; PULSE-GENERATOR AB Activation of the luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor (LHR) in cultured hypothalamic cells and immortalized GnRH ( gonadotropin-releasing hormone) neurons (GT1-7 cells) transiently stimulates and subsequently inhibits cAMP production and pulsatile GnRH release. The marked and delayed impairment of cAMP signaling and episodic GnRH release in GT1-7 cells is prevented by pertussis toxin (PTX). This, and the LH-induced release of membrane-bound G alpha(s) and G alpha(i3) subunits, are indicative of differential G protein coupling to the LHR. Action potential (AP) firing in identified GnRH neurons also initially increased and then progressively decreased during LH treatment. The inhibitory action of LH on AP firing was also prevented by PTX. Reverse transcriptase-PCR analysis of GT1-7 neurons revealed the expression of G protein-gated inwardly rectifying potassium (GIRK) channels in these cells. The LH-induced currents were inhibited by PTX and were identified as GIRK currents. These responses indicate that agonist stimulation of endogenous LHR expressed in GnRH neurons activates GIRK channels, leading to suppression of membrane excitability and inhibition of AP firing. These findings demonstrate that regulation of GIRK channel function is a dominant factor in gonadotropin-induced abolition of pulsatile GnRH release. Furthermore, this mechanism could contribute to the suppression of pituitary function during pregnancy. C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Mores, N (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A-36, Bethesda, MD 20892 USA. EM lazar@mail.nih.gov OI MORES, Nadia/0000-0002-4197-0914 FU Intramural NIH HHS NR 59 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25231 EP 25240 DI 10.1074/jbc.M603768200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300024 PM 16825187 ER PT J AU Vazquez, G Bird, GSJ Mori, Y Putney, JW AF Vazquez, Guillermo Bird, Gary St. J. Mori, Yasuo Putney, James W., Jr. TI Native TRPC7 channel activation by an inositol trisphosphate receptor-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DT40 B-LYMPHOCYTES; TRANSIENT RECEPTOR; 1,4,5-TRISPHOSPHATE RECEPTORS; CATION CHANNELS; PROTEIN; CELLS; ENTRY; EXPRESSION AB In DT40 B lymphocytes, Canonical Transient Receptor Potential 7 (TRPC7) functions as a diacylglycerol-activated non-selective cation channel. However, previous work indicated that the non-store-operated Ca2+ entry in this cell type depends upon inositol trisphosphate receptors ( IP3R). With the cell-attached configuration oleyl-acetyl-glycerol (OAG) induced single channel activity ( 75 pS) that was not observed in TRPC7(-/-) cells but was rescued by expression of TRPC7 under conditions expected to produce relatively low levels of expression ((LowT7)TRPC7(-/-)). A DT40 cell line lacking IP3R (IP3R-/- cells) showed no OAG-induced single channel activity, but this activity was rescued by transient expression of an IP3R ((IP3R-/-)-I-IP3R). Single channel properties in (LowT7)TRPC7(-/-) or (IP3R-/-)-I-IP3R DT40 cells were indistinguishable from one another and from wildtype cells. Thus, TRPC7 forms, or is part of, the channel underlying endogenous diacylglycerol-activated currents in DT40 B lymphocytes, and this activity of native TRPC7 requires IP3R. However, with conditions expected to produce greater expression levels, TRPC7 functioned independently of the presence of IP3R. This finding may serve to resolve previously conflicting reports from expression studies of TRPC channels. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Mol Biol Lab, Kyoto 6158510, Japan. RP Vazquez, G (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM vazquez1@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 26 TC 29 Z9 30 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25250 EP 25258 DI 10.1074/jbc.M604994200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300026 PM 16822861 ER PT J AU Nitto, T Dyer, KD Czapiga, M Rosenberg, HF AF Nitto, Takeaki Dyer, Kimberly D. Czapiga, Meggan Rosenberg, Helene F. TI Evolution and function of leukocyte RNase A ribonucleases of the avian species, Gallus gallus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EOSINOPHIL-DERIVED NEUROTOXIN; AMINO-ACID-SEQUENCE; SALMONELLA-ENTERITIDIS; ANTIMICROBIAL PROTEIN; MOLECULAR RECOGNITION; CHICKEN HETEROPHILS; CATIONIC PROTEIN; RANA-CATESBEIANA; RAPID EVOLUTION; IGUANA-IGUANA AB In this study, we explore the evolution and function of two closely related RNase A ribonucleases from the chicken, Gallus gallus. Separated by similar to 10 kb on chromosome 6, the coding sequences of RNases A-1 and A-2 are diverging under positive selection pressure (d(N) > d(S)) but remain similar to one another ( 81% amino acid identity) and to the mammalian angiogenins. Immunoreactive RNases A-1 and A-2 ( both similar to 16 kDa) were detected in peripheral blood granulocytes and bone marrow. Recombinant proteins are ribonucleolytically active (k(cat) = 2.6 and 0.056 s(-1), respectively), and surprisingly, both interact with human placental ribonuclease inhibitor. RNase A-2, the more cationic (pI 11.0), is both angiogenic and bactericidal; RNase A-1 ( pI 10.2) has neither activity. We demonstrated via point mutation of the catalytic His(110) that ablation of ribonuclease activity has no impact on the bactericidal activity of RNase A-2. We determined that the divergent domains II ( amino acids 71 - 76) and III ( amino acids 89 - 104) of RNase A-2 are both important for bactericidal activity. Furthermore, we demonstrated that these cationic domains can function as independent bactericidal peptides without the tertiary structure imposed by the RNase A backbone. These results suggest that ribonucleolytic activity may not be a crucial constraint limiting the ongoing evolution of this gene family and that the ribonuclease backbone may be merely serving as a scaffold to support the evolution of novel, non-ribonucleolytic proteins. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov FU NIAID NIH HHS [AI000942] NR 56 TC 41 Z9 46 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25622 EP 25634 DI 10.1074/jbc.M604313200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300065 PM 16803891 ER PT J AU Lammerding, J Fong, LG Ji, JY Reue, K Stewart, CL Young, SG Lee, RT AF Lammerding, Jan Fong, Loren G. Ji, Julie Y. Reue, Karen Stewart, Colin L. Young, Stephen G. Lee, Richard T. TI Lamins A and C but not lamin B1 regulate nuclear mechanics SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; GILFORD-PROGERIA-SYNDROME; DILATED CARDIOMYOPATHY; BUILDING-BLOCKS; HUMAN-DISEASE; PRELAMIN-A; ENVELOPE; CELLS; LAMINOPATHIES; MUTATIONS AB Mutations in the nuclear envelope proteins lamins A and C cause a broad variety of human diseases, including Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, and Hutchinson-Gilford progeria syndrome. Cells lacking lamins A and C have reduced nuclear stiffness and increased nuclear fragility, leading to increased cell death under mechanical strain and suggesting a potential mechanism for disease. Here, we investigated the contribution of major lamin subtypes (lamins A, C, and B1) to nuclear mechanics by analyzing nuclear shape, nuclear dynamics over time, nuclear deformations under strain, and cell viability under prolonged mechanical stimulation in cells lacking both lamins A and C, cells lacking only lamin A (i.e. "lamin C-only" cells), cells lacking wild-type lamin B1, and wild-type cells. Lamin A/C-deficient cells exhibited increased numbers of misshapen nuclei and had severely reduced nuclear stiffness and decreased cell viability under strain. Lamin C-only cells had slightly abnormal nuclear shape and mildly reduced nuclear stiffness but no decrease in cell viability under strain. Interestingly, lamin B1-deficient cells exhibited normal nuclear mechanics despite having a significantly increased frequency of nuclear blebs. Our study indicates that lamins A and C are important contributors to the mechanical stiffness of nuclei, whereas lamin B1 contributes to nuclear integrity but not stiffness. C1 Harvard Univ, Sch Med, Div Cardiovasc, Dept Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02139 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angelese Healthcare Syst, Los Angeles, CA 90073 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Lammerding, J (reprint author), Partners Res Facil, Rm 283,65 Landsdowne St, Cambridge, MA 02139 USA. EM jlammerding@rics.bwh.harvard.edu RI Lammerding, Jan/A-9498-2016 OI Lammerding, Jan/0000-0003-4335-8611 FU NCI NIH HHS [CA099506]; NHLBI NIH HHS [HL073809, HL64858, R01 HL082792]; NIAID NIH HHS [AI05438]; NIAMS NIH HHS [AR050200] NR 42 TC 199 Z9 203 U1 1 U2 29 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2006 VL 281 IS 35 BP 25768 EP 25780 DI 10.1074/jbc.M513511200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077LQ UT WOS:000240031300079 PM 16825190 ER PT J AU Tang, C Clore, GM AF Tang, Chun Clore, G. Marius TI A simple and reliable approach to docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE protein docking; sparse NOE data; reverse isotope labeling; deuteration; 'reduced' radius of gyration; rigid body minimization ID PHOSPHORYL TRANSFER COMPLEX; POTATO CARBOXYPEPTIDASE INHIBITOR; MANNITOL TRANSPORTER IIMANNITOL; SUGAR PHOSPHOTRANSFERASE SYSTEM; RESIDUAL DIPOLAR COUPLINGS; NUCLEAR-MAGNETIC-RESONANCE; 3-DIMENSIONAL STRUCTURE; MOLECULAR-DYNAMICS; TERMINAL DOMAIN; CROSS-LINKING AB A simple and reliable approach for docking protein-protein complexes from very sparse NOE-derived intermolecular distance restraints (as few as three from a single point) in combination with a novel representation for an attractive potential between mapped interaction surfaces is described. Unambiguous assignments of very sparse intermolecular NOEs are obtained using a reverse labeling strategy in which one the components is fully deuterated with the exception of selective protonation of the delta-methyl groups of isoleucine, while the other component is uniformly C-13-labeled. This labeling strategy can be readily extended to selective protonation of Ala, Leu, Val or Met. The attractive potential is described by a 'reduced' radius of gyration potential applied specifically to a subset of interfacial residues (those with an accessible surface area >= 50% in the free proteins) that have been delineated by chemical shift perturbation. Docking is achieved by rigid body minimization on the basis of a target function comprising the sparse NOE distance restraints, a van der Waals repulsion potential and the 'reduced' radius of gyration potential. The method is demonstrated for two protein-protein complexes (EIN-HPr and IIA(Glc)-HPr) from the bacterial phosphotransferase system. In both cases, starting from 100 different random orientations of the X-ray structures of the free proteins, 100% convergence is achieved to a single cluster (with near identical atomic positions) with an overall backbone accuracy of similar to 2 angstrom. The approach described is not limited to NMR, since interfaces can also be mapped by alanine scanning mutagenesis, and sparse intermolecular distance restraints can be derived from double cycle mutagenesis, cross-linking combined with mass spectrometry, or fluorescence energy transfer. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 43 TC 25 Z9 25 U1 3 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2006 VL 36 IS 1 BP 37 EP 44 DI 10.1007/s10858-006-9065-2 PG 8 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 088HN UT WOS:000240802900004 PM 16967193 ER PT J AU Woldemichael, GM Vasselli, JR Gardella, RS McKee, TC Linehan, WM McMahon, JB AF Woldemichael, Girma M. Vasselli, James R. Gardella, Roberta S. McKee, Tawnya C. Linehan, W. Marston McMahon, James B. TI Development of a cell-based reporter assay for screening of inhibitors of hypoxia-inducible factor 2-induced gene expression SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE HIF-2; cell-based assay; reporter assay; hypoxia response element; VHL disease ID TUMOR-SUPPRESSOR GENE; SMALL-MOLECULE INHIBITORS; HIPPEL-LINDAU PROTEIN; FACTORS HIF-1-ALPHA; RENAL-CARCINOMA; GROWTH; IDENTIFICATION; HIF-2-ALPHA; PATHWAY; VHL AB Reporter cell lines have been developed for the identification of inhibitors of gene expression enhanced by hypoxia-inducible factor 2, which has been implicated as a transcription factor involved in the tumorigenesis of clear cell renal carcinoma. Stably transformed reporter clones of the human renal clear cell carcinoma cell line 786-O were generated by transfection or retroviral infection. Luciferase reporter expression in the vectors used was driven by either the natural human vascular endothelial growth factor (VEGF) promoter-enhancer or by the VEGF and the human endothelial nitric oxide synthase enhancers modulating minimal human cytomegalovirus promoter. Utility of the generated reporter cell lines was validated by introducing the von Hippel-Lindau protein complex and testing for reporter inducibility by hypoxia. The dynamic range in reporter activity under hypoxic stress was found to be at least 30- to 40-fold, with a signal-to-noise ratio of 60:1. Properties of the cell lines such as tolerance to up to 3% DMSO, signal stability with multiple in vitro passages, and utility in both 96- and 384-well plate formats indicated their suitability for use in a high-throughput screen. In addition, the potential use of these reporter lines in the evaluation of high-throughput screening hits in vivo in various mice models has been demonstrated. C1 NCI, Mol Targets Dev Program, Canc Res Ctr, Ft Detrick, MD 21702 USA. NCI, Clin Res Ctr, Urol Oncol Branch, Bethesda, MD USA. NCI Frederick, SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. RP McKee, TC (reprint author), NCI, Mol Targets Dev Program, Canc Res Ctr, Ft Detrick, MD 21702 USA. EM mckee@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N02-CO-12400] NR 29 TC 17 Z9 18 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD SEP PY 2006 VL 11 IS 6 BP 678 EP 687 DI 10.1177/1087057106289234 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 084XT UT WOS:000240568400011 PM 16858007 ER PT J AU Barnes, AM Chang, W Morello, R Cabral, WA Weis, MA Eyre, DR Makareeva, E Kouznetsova, N Leikin, S Uveges, TE Mulvihill, JJ Wilson, PL Sundaram, UT Lee, B Marini, JC AF Barnes, A. M. Chang, W. Morello, R. Cabral, W. A. Weis, M. A. Eyre, D. R. Makareeva, E. Kouznetsova, N. Leikin, S. Uveges, T. E. Mulvihill, J. J. Wilson, P. L. Sundaram, U. T. Lee, B. Marini, J. C. TI Recessive lethal form of osteogenesis imperfecta caused by null mutations in CRTAP. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NICHD, BEMB, NIH, Bethesda, MD USA. Baylor Coll Med, Waco, TX USA. Univ Washington, Seattle, WA 98195 USA. NICHD, SPB, NIH, Bethesda, MD USA. Univ Hosp Oklahoma, HSC, Norman, OK USA. VCU, MCV, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S45 EP S45 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300165 ER PT J AU Barsony, J Sagimura, Y Tian, Y Carter, EA Resnick, HE Verbalis, JG AF Barsony, J. Sagimura, Y. Tian, Y. Carter, E. A. Resnick, H. E. Verbalis, J. G. TI Chronic hyponatremia causes severe osteoporosis by increasing osteoclastic bone resorption. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. Georgetown Univ, Div Endocrinol & Metab, Washington, DC 20057 USA. MedStar Res Inst, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S110 EP S110 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300418 ER PT J AU Beck, GR Yi, M Camalier, CE Lucas, DA Zhou, M Hood, BL Veenstra, TD Stephens, RM Conrads, TP AF Beck, G. R. Yi, M. Camalier, C. E. Lucas, D. A. Zhou, M. Hood, B. L. Veenstra, T. D. Stephens, R. M. Conrads, T. P. TI A systems biology approach to understanding inorganic phosphate signaling in osteoblast. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Emory Univ, Sch Med, Atlanta, GA USA. NCI, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21701 USA. NCI, Lab Proteom & Analyt Technol, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S332 EP S332 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302407 ER PT J AU Bi, Y Kilts, T Inkson, C Shi, S Young, MF AF Bi, Y. Kilts, T. Inkson, C. Shi, S. Young, M. F. TI Identification of tendon stem cells and the implications for understanding ectopic ossification. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S133 EP S133 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301070 ER PT J AU Black, DM Bouxsein, ML McGowan, JA Ireland, C Majumdar, S Rosen, E Garnero, P Newitt, DC Palermo, L Rosen, CJ AF Black, D. M. Bouxsein, M. L. McGowan, J. A. Ireland, C. Majumdar, S. Rosen, E. Garnero, P. Newitt, D. C. Palermo, L. Rosen, C. J. TI PTH once weekly increases BMI and is mildly anabolic in postmenopausal osteopenic women: Results from the PTH once weekly research (POWR) study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIAMS, NIH, Bethesda, MD USA. Synarc, Lyon, France. St Josephs Hosp, Bangor, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S43 EP S43 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300159 ER PT J AU Boskey, A Kulkarni, AB Ling, Y Lukashova, L Spevak, L Haruyama, N Sreenath, T van der Meulen, MCH AF Boskey, A. Kulkarni, A. B. Ling, Y. Lukashova, L. Spevak, L. Haruyama, N. Sreenath, T. van der Meulen, M. C. H. TI Bone changes in the dentin sialophosphoprotein knockout mouse. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Hosp Special Surg, Musculoskeletal Integr Program, New York, NY 10021 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD USA. Cornell Univ, Ithaca, NY 14853 USA. RI Haruyama, Naoto/D-1993-2011; van der Meulen, Marjolein/D-1549-2010 OI Haruyama, Naoto/0000-0001-6225-5816; van der Meulen, Marjolein/0000-0001-6637-9808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S133 EP S133 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301071 ER PT J AU Cepollaro, C Lauretani, F Gozzini, A Masi, L Falchetti, A Del Monte, F Sala, SC Tanini, A Corsi, A Bandinelli, S Ferrucci, L Brandi, M AF Cepollaro, C. Lauretani, F. Gozzini, A. Masi, L. Falchetti, A. Del Monte, F. Sala, S. Carbonell Tanini, A. Corsi, A. Bandinelli, S. Ferrucci, L. Brandi, M. TI Relationship of volumetric BMD and structural parameters with ERalpha polymorphisms in men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Florence, Dept Internal Med, I-50121 Florence, Italy. Tuscany Hlth Reg Agcy, Florence, Italy. Azienda Sanit Firenze, Rehabil Unit, Florence, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S242 EP S242 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302051 ER PT J AU Chang, W Nou, D Marini, J AF Chang, W. Nou, D. Marini, J. TI Increased cell surface TGF-beta receptor on osteoblastic cells from Brtl mouse model for osteogenesis imperfecta. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NICHD, BEMB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S369 EP S369 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303100 ER PT J AU Cho, YK Demissie, S Karasik, D Dupuis, J Cupples, LA Kiel, DP AF Cho, Y. K. Demissie, S. Karasik, D. Dupuis, J. Cupples, L. A. Kiel, D. P. TI Polymorphisms in the endothelial nitric oxide synthase (NOS3) gene and bone mass in humans. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Boston Univ, Boston, MA 02215 USA. Harvard Univ, Sch Med, NHLBI, Program Genom Applicat, Boston, MA USA. Hebrew SeniorLife, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S242 EP S242 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302052 ER PT J AU Farhat, GN Newman, AB Sutton-Tyrrell, K Matthews, KA Boudreau, R Schwartz, AV Harris, T Tylavsky, F Visser, M Cauley, JA AF Farhat, G. N. Newman, A. B. Sutton-Tyrrell, K. Matthews, K. A. Boudreau, R. Schwartz, A. V. Harris, T. Tylavsky, F. Visser, M. Cauley, J. A. TI Bone mineral density and incident cardiovascular disease in older men and women: The health, aging, and body composition study (Health ABC). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN 38163 USA. Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015 OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S8 EP S8 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300025 ER PT J AU Funari, A Spica, E Michienzi, S Di Domenico, M Castellucci, A Robey, P Bianco, P Riminucci, M AF Funari, A. Spica, E. Michienzi, S. Di Domenico, M. Castellucci, A. Robey, P. Bianco, P. Riminucci, M. TI Differential modulation of GNAS transcripts and Gs alpha isoforms during growth and differentiation of bone marrow stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Aquila, I-67100 Laquila, Italy. Fdn Parco S Raffaele, Rome, Italy. NIDCR, NIH, DHHS, Bethesda, MD USA. Univ Roma La Sapienza, Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S391 EP S391 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303185 ER PT J AU Guo, X Yang, Y AF Guo, X. Yang, Y. TI Wnt/beta-catenin signaling controls chondrocyte hypertryphy by inhibiting PTHrP signaling. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S78 EP S78 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300299 ER PT J AU Inkson, CA Kuznetsov, S Robey, PG Young, MA AF Inkson, C. A. Kuznetsov, S. Robey, P. G. Young, M. A. TI Co-operative regulation of osteoblast function by wnt-induced secreated protein (WISP-1) and TGF-beta 1. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NIDCR, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S256 EP S256 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866302108 ER PT J AU Ishijima, M Arikawa-Hirasawa, E Matsunobu, T Yamada, Y AF Ishijima, M. Arikawa-Hirasawa, E. Matsunobu, T. Yamada, Y. TI Perlecan modulates FGF/FGFR signaling in development of the growth plate. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S12 EP S12 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300039 ER PT J AU Islam, MS Jiang, X Li, H Kronenberg, MS Adams, DJ Morasso, MM Lichtler, AC AF Islam, M. S. Jiang, X. Li, H. Kronenberg, M. S. Adams, D. J. Morasso, M. M. Lichtler, A. C. TI Characterization of a tissue-directed Dlx3 knock-out mouse. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Connecticut, Ctr Hlth, Dept Orthopaed, Farmington, CT USA. NIAMS, Dev Skin Biol Unit, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S154 EP S154 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301151 ER PT J AU Kalkwarf, H Zemel, B Lappe, J Shepherd, J Huange, X Frederic, M Oberfield, S Winer, K Gilsanz, V AF Kalkwarf, H. Zemel, B. Lappe, J. Shepherd, J. Huange, X. Frederic, M. Oberfield, S. Winer, K. Gilsanz, V. TI Tracking of bone mass and density during growth and maturation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Cincinnati Childrens Hosp, Cincinnati, OH USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Creighton Univ, Omaha, NE 68178 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Clin Trials & Survey Corp, Baltimore, MD USA. Columbia Univ, New York, NY 10027 USA. NICHD, Bethesda, MD USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S124 EP S124 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301036 ER PT J AU Kamiya, N Ward, T Ye, L Kobayashi, T Atsawasuwan, P Joiner, DM Waldorff, EI Kronenberg, HM Yamauchi, M Goldstein, S Feng, JQ Mishina, Y AF Kamiya, N. Ward, T. Ye, L. Kobayashi, T. Atsawasuwan, P. Joiner, D. M. Waldorff, E. I. Kronenberg, H. M. Yamauchi, M. Goldstein, S. Feng, J. Q. Mishina, Y. TI BMP signaling through type 1a receptor (BMPR1a/ALK3) regulates trabecular and cortical bone properties in an age, sex, and skeletal site dependent manner in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NIEHS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Univ Missouri, Sch Dent, Kansas City, MO 64110 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ N Carolina, Dent Res Ctr, Chapel Hill, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S77 EP S77 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300295 ER PT J AU Lang, TF Cauley, J Tylavsky, F Chen, H Harris, T AF Lang, T. F. Cauley, J. Tylavsky, F. Chen, H. Harris, T. TI Thigh muscle attenuation is associated with incident hip fracture: the health, aging and body composition (Health ABC) study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Tennessee, Memphis, TN 38163 USA. NIA, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S35 EP S35 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300129 ER PT J AU Lappe, J Gilsanz, V Kalkwarf, H Mahboubi, S Oberfield, S Shepherd, J Zemel, B Frederick, M Winer, K Haynatzki, G AF Lappe, J. Gilsanz, V. Kalkwarf, H. Mahboubi, S. Oberfield, S. Shepherd, J. Zemel, B. Frederick, M. Winer, K. Haynatzki, G. TI Physical activity and bone density in a large cohort of US children. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Creighton Univ, Osteoporosis Res Ctr, Omaha, NE 68178 USA. Childrens Hosp, Los Angeles, CA 90027 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NICHD, Rockville, MD USA. Clin Trials & Survey Corp, Baltimore, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S104 EP S104 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300398 ER PT J AU Samelson, EJ Broe, KE Lu, M Hannan, MT Cupples, LA O'Donnell, CJ Kiel, DP AF Samelson, E. J. Broe, K. E. Lu, M. Hannan, M. T. Cupples, L. A. O'Donnell, C. J. Kiel, D. P. TI Vascular calcification and risk of hip fracture: The Framingham study. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 HSL, Inst Aging Res, Boston, MA USA. BUSPH, Boston, MA USA. NHLBI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S69 EP S69 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300263 ER PT J AU Shepherd, JA Lu, Y Zhao, S Gilsanz, V Kalkwarf, H Lappe, J Oberfield, S Zemel, B Fan, B Wren, T Fredrick, M Winer, K AF Shepherd, J. A. Lu, Y. Zhao, S. Gilsanz, V. Kalkwarf, H. Lappe, J. Oberfield, S. Zemel, B. Fan, B. Wren, T. Fredrick, M. Winer, K. TI Fracture risk is associated with race, height, and bone mineral density in healthy children. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Cincinnati Childrens Med Ctr, Cincinnati, OH USA. Creighton Univ, Omaha, NE 68178 USA. Columbia Univ, New York, NY 10027 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. CTASC, Baltimore, MD USA. NICHD, Bethesda, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S20 EP S20 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300069 ER PT J AU Sugimura, Y Verbalis, JG Barsony, J AF Sugimura, Y. Verbalis, J. G. Barsony, J. TI Effects of hyponatremia alone and combined hyponatremia and hypoosmolarity to increase osteoclast formation and resorptive activity in RAW264.7 cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Georgetown Univ, Div Endocrinol & Metab, Washington, DC 20057 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S167 EP S167 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301202 ER PT J AU Wickerham, DL Costantino, JP Vogel, V Cronin, W Cecchini, R Ford, L Wolmark, N AF Wickerham, D. L. Costantino, J. P. Vogel, V. Cronin, W. Cecchini, R. Ford, L. Wolmark, N. TI Fracture results from the study of tamoxifen and raloxifene (STAR). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NSABP Operat Ctr, Pittsburgh, PA USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S350 EP S350 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866303028 ER PT J AU Xiao, Z Camalier, CE Nagashima, K Chan, KC Lucas, DA de la Cruz, MJ Gignac, M Lockett, S Issaq, HJ Veenstra, TD Conrads, TP Beck, GR AF Xiao, Z. Camalier, C. E. Nagashima, K. Chan, K. C. Lucas, D. A. de la Cruz, M. J. Gignac, M. Lockett, S. Issaq, H. J. Veenstra, T. D. Conrads, T. P. Beck, G. R. TI Analysis of the extracellular matrix vesicle proteome in mineralizing osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 NCI, SAIC, Lab Proteom & Analyt Technol, Frederick, MD 21701 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. NCI, SAIC, Image Anal Lab, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S127 EP S127 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866301049 ER PT J AU Zemel, B Mahboubi, S Kalkwarf, H Gilsanz, V Shepherd, J Oberfield, S Lappe, J Frederick, M Winer, K AF Zemel, B. Mahboubi, S. Kalkwarf, H. Gilsanz, V. Shepherd, J. Oberfield, S. Lappe, J. Frederick, M. Winer, K. TI Bone age deviates from chronological age in contemporary US children. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 28th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 15-19, 2006 CL Philadelphia, PA SP Amer Soc Bone & Mineral Res C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Cincinnati Childrens Med Ctr, Cincinnati, OH USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Columbia Univ, New York, NY 10027 USA. Creighton Univ, Omaha, NE 68178 USA. Clin Trials & Survey Corp, Baltimore, MD USA. NICHD, Bethesda, MD USA. RI Zemel, Babette/D-1117-2009 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2006 VL 21 SU 1 BP S21 EP S21 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 089FS UT WOS:000240866300073 ER PT J AU Kellen, JC Schron, EB Milne, J Chandler, ML Berg, CM Ritchie, DA Paterson, D Sweeney, PA Nelson, JD Mickel, M AF Kellen, Joyce C. Schron, Eleanor B. Milne, Jill Chandler, Mary L. Berg, Claire M. Ritchie, Deborah A. Paterson, Diana Sweeney, Patricia A. Nelson, Joy D. Mickel, Mary CA AFFIRM Investigators Coordinators TI Perceived effects on patients' health of participation in the atrial fibrillation follow-up investigation of rhythm management study SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE AFFIRM; atrial fibrillation; clinical trial; patient satisfaction; survey ID CLINICAL-TRIAL; SATISFACTION; ATTITUDES; THERAPY; AFFIRM; PERCEPTIONS; DISEASE; STROKE AB Background: Patients' views about participation in clinical trials have been explored using end-of-study questionnaires for various disease entities. However, little is known about why individuals with atrial fibrillation (AF) choose to participate in clinical trials or how they view their research experience. Understanding these perceptions should provide valuable information for future studies in developing methods to enhance enrollment, optimize adherence to therapies, and maximize patient retention. Methods: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study was a randomized trial of rate-control versus rhythm-control for the management of AF. This descriptive ancillary study used a 7-item questionnaire comprising closed and open-ended items that explored: (1) perceptions of benefits from participation, (2) motivation for enrolling, and (3) satisfaction with research staff and operations. Results: A total of 741/1,032 participants (72%) at 34 of 213 participating AFFIRM sites responded, representing 18% of the 4,060 patients enrolled. The mean follow-up of these respondents was 3.8 +/- 1.1 years. Most respondents (91%) felt that they received enough information about AFFIRM before enrolling and that the results would benefit themselves (88%) and others (91%). Most respondents felt study participation improved awareness about AF (90%) and facilitated coordination of their healthcare (89%). Virtually all were satisfied with information received from AFFIRM personnel (96%), and most (98%) reported that they had received "good care." Responses were similar between randomization groups (rate-control or rhythm-control) and between those younger than 65 years and those 65 years or older. Participants in sinus rhythm at last follow-up were more likely to believe that their medical care in AFFIRM was better than what they would otherwise have received, and were more likely to perceive their treatment course as entailing fewer emergency room visits, hospitalizations, and doctor visits. Regularly scheduled appointments and ongoing availability of staff to answer questions appeared to increase participants' confidence and reduce anxiety. Conclusions: Patients enrolled in a long-term clinical trial for management of AF were overwhelmingly satisfied with participation. C1 NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Div Cardiovasc Dis, Bethesda, MD 20892 USA. Univ Calgary, Fac Med, Cardiovasc Res Grp, Calgary, AB, Canada. Axio Res Corp, Seattle, WA USA. Maine Med Ctr, Portland, ME 04102 USA. Cleveland Med Ctr, Cleveland, OH USA. RP Schron, EB (reprint author), NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Div Cardiovasc Dis, 6701 Rockledge Dr,Room 8144,MSC 7936, Bethesda, MD 20892 USA. EM schrone@nih.gov FU NHLBI NIH HHS [N01-HC-55139] NR 31 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD SEP-OCT PY 2006 VL 21 IS 5 BP 388 EP 396 PG 9 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 083QE UT WOS:000240472500013 PM 16966916 ER PT J AU Lee, DW Wu, XF Eisenberg, E Greene, LE AF Lee, Dong-won Wu, Xufeng Eisenberg, Evan Greene, Lois E. TI Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis SO JOURNAL OF CELL SCIENCE LA English DT Article DE GAK; auxilin; clathrin; dynamin; TIRF ID AP-2 ADAPTER COMPLEX; MEDIATED ENDOCYTOSIS; UNCOATING ATPASE; PHOSPHOINOSITIDE METABOLISM; PLASMA-MEMBRANE; LIVING CELLS; PROTEIN; VESICLES; EXCHANGE; INVAGINATION AB Cyclin G-associated kinase (GAK), the ubiquitous form of the neuronal-specific protein auxilin 1, is an essential cofactor for Hsc70-dependent uncoating of clathrin-coated vesicles. Total internal reflectance microscopy was used to determine the timing of GAK binding relative to dynamin and clathrin binding during invagination of clathrin-coated pits. Following transient recruitment of dynamin to the clathrin puncta, large amounts of GAK are transiently recruited. GAK and clathrin then disappear from the evanescent field as the pit invaginates from the plasma membrane and finally these proteins disappear from the epifluorescence field, probably as the clathrin is uncoated from the budded vesicles by Hsc70. The recruitment of GAK is dependent on its PTEN-like domain, which we found binds to phospholipids. This suggests that interaction with phospholipids is essential for recruitment of GAK and, in turn, Hsc70, but Hsc70 recruitment alone might not be sufficient to induce irreversible clathrin uncoating. When budding of clathrin-coated pits is inhibited by actin depolymerization, there is repeated flashing of GAK on the clathrin-coated pit but neither scission nor irreversible uncoating occur. Therefore, budding as well as synchronous recruitment of GAK might be required for irreversible clathrin uncoating. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov NR 37 TC 66 Z9 67 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP 1 PY 2006 VL 119 IS 17 BP 3502 EP 3512 DI 10.1242/jcs.03092 PG 11 WC Cell Biology SC Cell Biology GA 082JS UT WOS:000240383500004 PM 16895969 ER PT J AU Messner, DJ Romeo, C Boynton, A Rossie, S AF Messner, Donald J. Romeo, Charles Boynton, Alton Rossie, Sandra TI Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE okadaic acid; ser/thr protein phosphatase; PP2A; PP5; p53; tumor promotion ID PROTEIN PHOSPHATASE 2A; SMALL-T-ANTIGEN; INDUCED GROWTH SUPPRESSION; DNA-DAMAGE RESPONSE; WILD-TYPE P53; GLUCOCORTICOID RECEPTOR; TUMOR-SUPPRESSOR; SERINE/THREONINE PHOSPHATASES; ADENOVIRUS VECTORS; CYCLE PROGRESSION AB The microbial toxin okadaic acid (OA) specifically inhibits PPP-type ser/thr protein phosphatases. OA is an established tumor promoter with numerous cellular effects that include p53-mediated cell cycle arrest. In T51 B rat liver epithelial cells, a model useful for tumor promotion studies, p53 activation is induced by tumor-promoting (low nanomolar) concentrations of OA. Two phosphatases sensitive to these concentrations of OA, PP2A and protein phosphatase 5 (PP5), have been implicated as negative regulators of p53. In this study we examined the respective roles of these phosphatases in p53 activation in non-neoplastic T51 B cells. Increases in p53 activity were deduced from levels of p21 (cip1) and/or the rat orthologue of mdm2, two p53-regulated gene products whose induction was blocked by siRNA-mediated knockdown of p53. As observed with 10 nM OA, both phospho-ser15-p53 levels and p53 activity were increased by 10 mu M fostriecin or SV40 small t-antigen. Both of these treatments selectively inhibit PP2A but not PP5. siRNA-mediated knockdown of PP2A, but not PP5, also increased p53 activity. Finally, adenoviral-mediated overexpression of an OA-resistant form of PP5 did not prevent increased phospho-ser15-p53, p53 protein, or p53 activity caused by 10 nM OA. Together these results indicate that PP5 blockade is not responsible for OA-induced p53 activation and G, arrest in T51 B cells. In contrast, specific blockade of PP2A mimics p53-related responses to OA in T51 B cells, suggesting that PP2A is the target for this response to OA. C1 Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. NW Biotherapeut, Bothell, WA USA. RP Rossie, S (reprint author), Purdue Univ, Dept Biochem, 175 S Univ St, W Lafayette, IN 47907 USA. EM rossie@purdue.edu FU NCI NIH HHS [CA039745]; NINDS NIH HHS [NS031221] NR 62 TC 13 Z9 15 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 2006 VL 99 IS 1 BP 241 EP 255 DI 10.1002/jcb.20919 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 077TE UT WOS:000240052400023 PM 16598789 ER PT J AU Lambert, JR Kelly, JA Shim, M Huffer, WE Nordeen, SK Baek, SJ Eling, TE Lucia, MS AF Lambert, James R. Kelly, Julie A. Shim, Minsub Huffer, William E. Nordeen, Steven K. Baek, Seung Joon Eling, Thomas E. Lucia, M. Scott TI Prostate derived factor in human prostate cancer cells: Gene induction by vitamin D via a p53-dependent mechanism and inhibition of prostate cancer cell growth SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BETA SUPERFAMILY MEMBER; BONE MORPHOGENETIC PROTEIN; DRUG-ACTIVATED GENE; EPITHELIAL-CELLS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; RETINOIC ACID; TUMOR-CELLS; EXPRESSION; CYTOKINE-1; P53 AB The secosteroid hormone 1 alpha, 25-dihydroxyvitamin D-3 (1,25D) has been shown to regulate the growth and differentiation of human prostate cancer (PCa) cells, although the precise molecular mechanisms mediating these effects have not been defined. Previous studies in our laboratory demonstrated that the anti proliferative effects of 1,25D on PCa cells are mediated through the nuclear vitamin D receptor (VDR). In the present study, we performed gene profiling of LNCaP human PCa cells following 1,25D treatment and identified the antitumorigenic gene, prostate derived factor (PDF), as being highly induced by 1,25D. PDF is a member of the TGF-beta superfamily and has been implicated in a variety of functions directly related to tumorigenicity including antiproliferative and pro-apoptotic effects. Gene expression studies using 1,25D analogs and a VDR antagonist demonstrate that 1,25D-mediated induction of PDF message and protein in PCa cells is dependent on VDR action. PDF is a transcriptional target of the tumor suppressor, p53. Here we show that the expression of PDF in nine PCa cell lines is dependent on functional p53. Additionally, transfection of p53-null ALVA-31 PCa cells with a p53 expression plasmid, and expression of dominant negative p53 in LNCaP PCa cells, show that the ability of VDR to induce PDF requires functional p53. Importantly, forced PDF expression in PC-3 cells results in decreased cell proliferation, soft agar cloning, and xenograft tumor size. These data demonstrate that PDF exerts antitumorigenic properties on PCa cells and its regulation by 1,25D may provide insights into the action of 1,25D in PCa. C1 Univ Colorado, Hlth Sci Ctr, Dept Pathol, Aurora, CO 80045 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37901 USA. RP Lambert, JR (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pathol, Mail Stop 8104,RC-1 S,12801 E 17th Ave,Room L18-5, Aurora, CO 80045 USA. EM jim.lambert@uchse.edu OI Baek, Seung/0000-0001-7866-7778 FU Intramural NIH HHS NR 46 TC 45 Z9 45 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2006 VL 208 IS 3 BP 566 EP 574 DI 10.1002/jcp.20692 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 068YW UT WOS:000239412300010 PM 16741990 ER PT J AU Neithardt, A Farshori, MP Shah, FB Catt, KJ Shah, BH AF Neithardt, Adrienne Farshori, M. Parvaiz Shah, Farzana B. Catt, Kevin J. Shah, Bukhtiar H. TI Dependence of GnRH-induced phosphorylation of CREB and BAD on EGF receptor transactivation in GT1-7 neuronal cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; EPIDERMAL-GROWTH-FACTOR; SIGNALING PATHWAYS; PHOSPHOINOSITIDE 3-KINASE; KINASE ACTIVATION; TYROSINE KINASES; PROTEIN-KINASES; ANGIOTENSIN-II; CANCER-CELLS; C-FOS AB The hypothalamic neuropeptide, gonadotropin releasing hormone (GnRH), is a primary regulatory factor in the neuroendocrine control of reproduction. The GnRH decapeptide is released in an episodic manner from hypothalamic GnRH neurons, which are known to express GnRH receptors. Here we examined the signaling pathways by which autocrine GnRH stimulation generates cell survival and proliferative signals in hypothalamic GT1-7 cells. Both GnRH and epidermal growth factor (EGF) caused rapid phosphorylation of cyclic AMP response element binding protein (CREB) and BAD. The selective epidermal growth factor receptor (EGF-R) antagonist, AG1478, attenuates the phosphorylation of these proteins by GnRH and EGF. Inhibition of PKC and Src abolished the stimulatory effects of GnRH, but not that of EGF, consistent with a critical role of these signaling molecules upstream of the EGF-R. All of these effects of GnRH were mimicked by phorbol 12 myristate 13'-acetate (PMA). Consistent with the prosurvival and mitogenic effects of phosphoinositide 3-kinase/Akt (Pl3-K/Akt) downstream of the EGF-R, inhibition of Pl3-K diminished the activation of these proteins following stimulation with GnRH, EGF, and PMA. Overexpression of dominant negative Akt attenuated agonist-induced phosphorylation of BAD, but not that of ERK1/2 and CREB. Moreover, overexpression of wild-type RSK-1 resulted in enhanced basal as well as agonist-induced phosphorylation of CREB and BAD, indicating a critical role of RSK-1 in activating cytosolic as well as nuclear proteins. These data reveal novel signaling mechanisms of GnRH-induced phosphorylation of CREB and BAD in GT1-7 neurons through transactivation of the EGF-R. C1 NICHHD, Sect Hormonal Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHHD, Sect Hormonal Regulat, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov FU Intramural NIH HHS NR 51 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2006 VL 208 IS 3 BP 586 EP 593 DI 10.1002/j.jcp.20697 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 068YW UT WOS:000239412300012 PM 16741954 ER PT J AU Schwartz, AV Sellmeyer, DE Vittinghoff, E Palermo, L Lecka-Czernik, B Feingold, KR Strotmeyer, ES Resnick, HE Carbone, L Beamer, BA Park, SW Lane, NE Harris, TB Cummings, SR AF Schwartz, Ann V. Sellmeyer, Deborah E. Vittinghoff, Eric Palermo, Lisa Lecka-Czernik, Beata Feingold, Kenneth R. Strotmeyer, Elsa S. Resnick, Helaine E. Carbone, Laura Beamer, Brock A. Park, Seok Won Lane, Nancy E. Harris, Tamara B. Cummings, Steven R. CA Hlth Aging Body Composition Hlth A TI Thiazolidinedione use and bone loss in older diabetic adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-COMPOSITION; MINERAL DENSITY; ADIPOSE-TISSUE; INCREASED RISK; FRACTURE RISK; ROSIGLITAZONE; TROGLITAZONE; WOMEN; MELLITUS; THERAPY AB Context: Activation of peroxisome proliferator-activated receptor-gamma by thiazolidinediones (TZDs) results in lower bone mass in mice. Objective: The objective of the study was to determine whether TZD use is associated with changes in bone mineral density (BMD) in older adults with type 2 diabetes. Design: We analyzed 4-yr follow-up data from the Health, Aging, and Body Composition observational study. Setting: The study was conducted in a general community. Patients: White and black, physically able men and women, aged 70-79 yr at baseline with diabetes defined by self-report, use of hypoglycemic medication, elevated fasting glucose (>= 126 mg/dl), or elevated 2-h glucose tolerance test (>= 200 mg/dl) participated in the study. Main Outcome Measures: Whole-body, lumbar spine (derived from whole body), and hip BMD were measured by dual-energy x-ray absorptiometry at 2-yr intervals. Results: Of 666 diabetic participants, 69 reported TZD use at an annual visit, including troglitazone (n = 22), pioglitazone (n = 30), and/or rosiglitazone (n = 31). Those with TZD use had higher baseline hemoglobin A(1c) and less weight loss over 4 yr but similar baseline BMD and weight than others with diabetes. In repeated-measures models adjusted for potential confounders associated with TZD use and BMD, each year of TZD use was associated with greater bone loss at the whole body [additional loss of -0.61% per year; 95% confidence interval (CI) -1.02, -0.21% per year], lumbar spine (-1.23% per year; 95% CI -2.06, -0.40% per year), and trochanter (-0.65% per year; 95% CI -1.18, -0.12% per year) in women, but not men, with diabetes. Conclusion: These observational results suggest that TZDs may cause bone loss in older women. These results need to be tested in a randomized trial. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94107 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94107 USA. Univ Arkansas Med Sci, Dept Geriatr, Reynolds Inst Aging, Little Rock, AR 72202 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. MedStar Res Inst, Dept Epidemiol, Landover, MD 20785 USA. Univ Tennessee, Div Rheumatol, Dept Med, Memphis, TN 38163 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Pochon CHA Univ, Dept Med, Seoul 135081, South Korea. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94120 USA. RP Schwartz, AV (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Lobby 4,Suite 5700, San Francisco, CA 94107 USA. EM aschwartz@psg.ucsf.edu RI Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036 FU Intramural NIH HHS; NIA NIH HHS [R01 AG17482, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01 AG017482]; NIDDK NIH HHS [P50 DK064538] NR 30 TC 257 Z9 280 U1 0 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2006 VL 91 IS 9 BP 3349 EP 3354 DI 10.1210/jc.2005-2226 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 082AL UT WOS:000240358600017 PM 16608888 ER PT J AU El-Gharbawy, AH Adler-Wailes, DC Mirch, MC Theim, KR Ranzenhofer, L Tanofsky-Kraff, M Yanovski, JA AF El-Gharbawy, Areeg H. Adler-Wailes, Diane C. Mirch, Margaret C. Theim, Kelly R. Ranzenhofer, Lisa Tanofsky-Kraff, Marian Yanovski, Jack A. TI Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID AIR-DISPLACEMENT PLETHYSMOGRAPHY; BINGE-EATING DISORDER; BODY-COMPOSITION; MENTAL-RETARDATION; DEPRESSED-PATIENTS; HUMAN PLATELETS; ENERGY-BALANCE; OBESITY; BDNF; PSYCHOPATHOLOGY AB Context: Brain-derived neurotrophic factor (BDNF) and its receptor appear to be important components of the leptin-signaling cascade involved in energy homeostasis, and mice with BDNF or TrkB gene haploinsufficiency have excessive adiposity. Little is known about the relationship between adiposity and BDNF, particularly in children. Objective: The objective of the study was to study the association of serum BDNF with measures of adiposity in children. Design/Setting/Patients: BDNF was determined by a sandwich-type ELISA after an overnight fast in convenience sample of 328 subjects, aged 3-19 yr enriched for extreme obesity. In 43, BDNF was also measured before, and again 1 h after, consuming a high-energy content (787 kcal) milkshake. Main Outcome Measures: Measures included associations between BDNF and measures of adiposity. Results: There were no significant univariate associations between log BDNF and adiposity measured by body mass index (BMI), BMI-Z score, or fat mass. However, in an analysis of covariance accounting for age, sex, race, pubertal status, and platelet count, BDNF was lower in overweight children (mean +/- SD, 39.8 +/- 24.8 vs. 47.0 +/- 25.4 ng/dl, P = 0.03); in multiple regression analyses with log BDNF as the dependent variable, BMI (P = 0.03), BMI-Z (P = 0.01), and body fat (P < 0.02) were all negatively associated with BDNF once age, pubertal status, and platelet count were included in the model. Ingestion of a meal did not significantly alter serum BDNF 1 h later (P = 0.26). Conclusions: Serum BDNF is lower in extremely overweight children and adolescents than those of normal weight. It remains to be determined whether obese individuals with low serum BDNF for age and platelet count have mutations that alter BDNF function. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,DHHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NIH, Unit Growth & Obes, Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [HD-000641, Z01 HD000641] NR 41 TC 48 Z9 49 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2006 VL 91 IS 9 BP 3548 EP 3552 DI 10.1210/jc.2006-0658 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 082AL UT WOS:000240358600050 PM 16787984 ER PT J AU Bourdeau, I Matyakhina, L Stergiopoulos, SG Sandrini, F Boikos, S Stratakis, CA AF Bourdeau, Isabelle Matyakhina, Ludmila Stergiopoulos, Sotirios G. Sandrini, Fabiano Boikos, Sosipatros Stratakis, Constantine A. TI 17q22-24 Chromosomal losses and alterations of protein kinase A subunit expression and activity in adrenocorticotropin-independent macronodular adrenal hyperplasia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MCCUNE-ALBRIGHT-SYNDROME; ABNORMAL HORMONE-RECEPTORS; STIMULATORY G-PROTEIN; CARNEY COMPLEX; CUSHINGS-SYNDROME; REGULATORY SUBUNIT; ACTIVATING MUTATIONS; CYCLIC-AMP; PRKAR1A GENE; I-ALPHA AB Context: Primary adrenocortical hyperplasias leading to Cushing syndrome include primary pigmented nodular adrenocortical disease and ACTH-independent macronodular adrenal hyperplasia (AIMAH). Inactivating mutations of the 17q22-24-located PRKAR1A gene, coding for the type 1A regulatory subunit of protein kinase A (PKA), cause primary pigmented nodular adrenocortical disease and the multiple endocrine neoplasia syndrome Carney complex. PRKAR1A mutations and 17q22-24 chromosomal losses have been found in sporadic adrenal tumors and are associated with aberrant PKA signaling. Objective: The objective of the study was to examine whether somatic 17q22-24 changes, PRKAR1A mutations, and/ or PKA abnormalities are present in AIMAH. Patients: We studied fourteen patients with Cushing syndrome due to AIMAH. Methods: Fluorescent in situ hybridization with a PRKAR1A-specific probe was used for investigating chromosome 17 allelic losses. The PRKAR1A gene was sequenced in all samples, and tissue was studied for PKA activity, cAMP responsiveness, and PKA subunit expression. Results: We found 17q22-24 allelic losses in 73% of the samples. There were no PRKAR1A-coding sequence mutations. The RII beta PKA subunit was overexpressed by mRNA, whereas the RI alpha, RI beta, RII alpha, and C alpha PKA subunits were underexpressed. These findings were confirmed by immunohistochemistry. Total PKA activity and free PKA activity were higher in AIMAH than normal adrenal glands, consistent with the up-regulation of the RII beta PKA subunit. Conclusions: PRKAR1A mutations are not found in AIMAH. Somatic losses of the 17q22-24 region and PKA subunit and enzymatic activity changes show that PKA signaling is altered in AIMAH in a way that is similar to that of other adrenal tumors with 17q losses or PRKAR1A mutations. C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. CHU Montreal, Hotel Dieu, Dept Med, Div Endocrinol, Montreal, PQ H2W 1T8, Canada. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Levesque, Isabelle/A-1899-2012 FU Intramural NIH HHS NR 33 TC 31 Z9 32 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2006 VL 91 IS 9 BP 3626 EP 3632 DI 10.1210/jc.2005-2608 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 082AL UT WOS:000240358600061 PM 16772351 ER PT J AU Porter, FD AF Porter, Forbes D. TI Cholesterol precursors and facial clefting SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID LEMLI-OPITZ-SYNDROME; SONIC HEDGEHOG; BIOSYNTHESIS; DEFICIENCY; PROTEINS; MICE AB Iborn errors of cholesterol synthesis cause human malformation syndromes, including Smith-Lemli-Opitz syndrome, lathosterolosis, desmosterolosis, X-linked dominant chondrodysplasia punctata type 2, and congenital hemidysplasia with ichthyosiform erythroderma and limb defects. Because adequate cholesterol is not transported across the placenta, low cholesterol and elevated sterol precursor levels are present during embryogenesis. It has been debated whether the malformations result from low cholesterol or the buildup of sterol precursors. In this issue of the JCI, Engelking et al. provide evidence that sterol precursor accumulation plays a pivotal role in the genesis of facial malformations (see the related article beginning on page 2356). C1 NICHD, HDB, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Porter, FD (reprint author), NICHD, HDB, NIH, Dept Hlth & Human Serv, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov FU Intramural NIH HHS NR 17 TC 18 Z9 23 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2006 VL 116 IS 9 BP 2322 EP 2325 DI 10.1172/JCI29872 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082IT UT WOS:000240380700005 PM 16955133 ER PT J AU Gladwin, MT AF Gladwin, Mark T. TI Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SICKLE-CELL-DISEASE; NITRIC-OXIDE BIOAVAILABILITY; ARGININE METABOLISM; RELAXING FACTOR; BLOOD-VESSELS; HEMOGLOBIN; CIRCULATION; RELAXATION; MOUSE AB In this issue of the JCI, Stasch and colleagues suggest that a novel drug, BAY 58-2667, potently activates a pool of oxidized and heme-free soluble guanylyl cyclase (sGC; see the related article beginning on page 2552). The increased vasodilatory potency of BAY 58-2667 the authors found in a number of animal models of endothelial dysfunction and in human blood vessels from patients with diabetes suggests that there exists a subphenotype of endothelial dysfunction characterized by receptor-level NO resistance. Diseases associated with NO resistance would appear to be ideally suited for therapies directed at restoring redox homeostasis, sGC activity, and NO sensitivity. C1 NHLBI, Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 22 TC 41 Z9 46 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2006 VL 116 IS 9 BP 2330 EP 2332 DI 10.1172/JCI29807 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082IT UT WOS:000240380700008 PM 16955136 ER PT J AU Knollmann, BC Chopra, N Hlaing, T Akin, B Yang, T Ettensohn, K Knollmann, BEC Horton, KD Weissman, NJ Holinstat, I Zhang, W Roden, DM Jones, LR Franzini-Armstrong, C Pfeifer, K AF Knollmann, Bjorn C. Chopra, Nagesh Hlaing, Thinn Akin, Brandy Yang, Tao Ettensohn, Kristen Knollmann, Barbara E. C. Horton, Kenneth D. Weissman, Neil J. Holinstat, Izabela Zhang, Wei Roden, Dan M. Jones, Larry R. Franzini-Armstrong, Clara Pfeifer, Karl TI Casq2 deletion causes sarcoplasmic reticulum volume increase, premature Ca2+ release, and catecholaminergic polymorphic ventricular tachycardia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; CHANNEL RYANODINE RECEPTOR; CANINE CARDIAC CALSEQUESTRIN; CALCIUM-RELEASE; TRANSGENIC MICE; OVEREXPRESSING CALSEQUESTRIN; FAILING HEARTS; SUDDEN-DEATH; MUSCLE; MYOCYTES AB Cardiac calsequestrin (Casq2) is thought to be the key sarcoplasmic reticulum (SR) Ca2+ storage protein essential for SR Ca2+ release in mammalian heart. Human CASQ2 mutations are associated with catecholaminergic ventricular tachycardia. However, homozygous mutation carriers presumably lacking functional Casq2 display surprisingly normal cardiac contractility. Here we show that Casq2-null mice are viable and display normal SR Ca2+ release and contractile function under basal conditions. The mice exhibited striking increases in SR volume and near absence of the Casq2-binding proteins triadin-1 and junctin; upregulation of other Ca2+-binding proteins was not apparent. Exposure to catecholamines in Casq2-null myocytes caused increased diastolic SR Ca2+ leak, resulting in premature spontaneous SR Ca2+ releases and triggered beats. In vivo, Casq2-null mice phenocopied the human arrhythmias. Thus, while the unique molecular and anatomic adaptive response to Casq2 deletion maintains functional SR Ca2+ storage, lack of Casq2 also causes increased diastolic SR Ca2+ leak, rendering Casq2-null mice susceptible to catecholaminergic ventricular arrhythmias. C1 Vanderbilt Univ, Med Ctr, Oates Inst Expt Therapeut, Div Clin Pharmacol,Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Dept Med, Indianapolis, IN 46202 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. RP Knollmann, BC (reprint author), Vanderbilt Univ, Med Ctr, Oates Inst Expt Therapeut, Div Clin Pharmacol,Dept Med, 1265 Med Res Bldg 4, Nashville, TN 37232 USA. EM bjorn.knollmann@vanderbilt.edu OI Knollmann, Bjorn/0000-0003-4956-9735; Pfeifer, Karl/0000-0002-0254-682X FU Intramural NIH HHS; NHLBI NIH HHS [HL 48093, HL071670, HL28556, HL46681, P01 HL046681, R01 HL028556, R01 HL048093, R01 HL071670, R37 HL048093] NR 58 TC 238 Z9 244 U1 3 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2006 VL 116 IS 9 BP 2510 EP 2520 DI 10.1172/JCI29128 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 082IT UT WOS:000240380700027 PM 16932808 ER PT J AU Souza, IE Allen, JB Xiang, J Klinzman, D Diaz, R Zhang, S Chaloner, K Zdunek, D Hess, G Williams, CF Benning, L Stapleton, JT AF Souza, I. E. Allen, J. B. Xiang, J. Klinzman, D. Diaz, R. Zhang, S. Chaloner, K. Zdunek, D. Hess, G. Williams, C. F. Benning, L. Stapleton, J. T. TI Effect of primer selection on estimates of GB virus C (GBV-C) prevalence and response to antiretroviral therapy for optimal testing for GBV-C viremia SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEPATITIS-G VIRUS; HIV-INFECTED INDIVIDUALS; C/HEPATITIS-G VIRUS; QUALITY-CONTROL; VERTICAL TRANSMISSION; RNA; SURVIVAL; ASSOCIATION; COINFECTION; PROTEIN AB GB virus C (GBV-C; also called hepatitis G virus) is a common cause of infection associated with prolonged survival among HIV-infected individuals. The prevalences of GBV-C viremia vary widely in different studies, and there has been poor agreement among different laboratories performing GBV-C RNA detection in quality control studies. To determine the optimal method of measuring GBV-C RNA in clinical samples, samples obtained from 939 HIV-infected subjects were studied using reverse transcription (RT)-PCR methods amplifying four separate regions of the GBV-C genome. Primers amplifying the E2 coding region were 100% specific; however, their sensitivity was only 76.6%. In contrast, primers amplifying three additional conserved regions of the GBV-C genome (the 5' nontranslated region and the nonstructural protein-coding regions 3 and 5A) were more sensitive but produced higher rates of false-positive results. Using low-specificity primer sets influenced the significance of association between GBV-C viremia and response to antiretroviral therapy. Using a quantitative GBV-C RNA method, the GBV-C RNA concentration did not correlate with baseline or set point HIV RNA levels; however, a correlation between negative, low, and high GBV-C RNA levels and increasing reduction in HIV RNA following antiretroviral therapy was observed. Subjects with both GBV-C E2 antibody and viremia had significantly lower GBV-C RNA levels than did viremic subjects without E2 antibody. These studies demonstrate that accurate detection of GBV-C RNA by nested RT-PCR requires the use of primers representing multiple genome regions. Analyses based on testing with single primers do not lead to reliable conclusions about the association between GBV-C infection and clinical outcomes. C1 Univ Iowa, Roy & Lucille Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Iowa City Vet Adm Med Ctr, Iowa City, IA USA. Univ Fed Sao Paulo, Paulista Sch Med, Div Infect Dis, Sao Paulo, Brazil. Univ Iowa, Coll Publ Hlth, Dept Biostat, Iowa City, IA USA. Roche Diagnost GmbH, Penzberg, Germany. Roche Diagnost GmbH, Mannheim, Germany. NIAID, Epidemiol Branch, Div AIDS, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Stapleton, JT (reprint author), Univ Iowa, Roy & Lucille Carver Coll Med, Dept Internal Med, SW54-15,GH,200 Hawkins Dr, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu RI Chaloner, Kathryn/B-5090-2013 FU NCRR NIH HHS [M01 RR000083, M01 RR000071, M01-RR-00079, M01 RR000079, M01-RR-00071, M01-RR-00083]; NIAID NIH HHS [AI587401, U01 AI034989, U01 AI035004, U01-AI-34994, U01-AI-42590, U01-AI-31834, U01 AI034994, U01-AI-34993, U01 AI042590, U01-AI-35004, U01-AI-34989, U01 AI034993, U01 AI031834, AI50478]; OID CDC HHS [U01-CH-32632] NR 39 TC 26 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2006 VL 44 IS 9 BP 3105 EP 3113 DI 10.1128/JCM.02663-05 PG 9 WC Microbiology SC Microbiology GA 086YB UT WOS:000240708000007 PM 16954234 ER PT J AU Welzel, TM Miley, WJ Parks, TL Goedert, JJ Whitby, D Ortiz-Conde, BA AF Welzel, Tania M. Miley, Wendell J. Parks, Thomas L. Goedert, James J. Whitby, Denise Ortiz-Conde, Betty A. TI Real-time PCR assay for detection and quantification of hepatitis B virus genotypes A to G SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HBV MONITOR TEST; TAQMAN PCR; SURFACE-ANTIGEN; QUANTITATIVE-ANALYSIS; DETECTION SYSTEM; DNA; AMPLIFICATION; RELATEDNESS; EXTRACTION; STANDARD AB The detection and quantification of hepatitis B virus (HBV) DNA play an important role in diagnosing and monitoring HBV infection as well as assessing therapeutic response. The great variability among HBV genotypes and the enormous range of clinical HBV DNA levels present challenges for PCR-based amplification techniques. In this study, we describe the development, evaluation, and validation of a novel real-time PCR assay designed to provide accurate quantification of DNA from all eight HBV genotypes in patient plasma specimens. A computer algorithm was used to design degenerate real-time PCR primers and probes based upon a large number (n = 340) of full-length genomic sequences including HBV genotypes A to H from Europe, Africa, Asia, and North and South America. Genotype performance was tested and confirmed using 59 genotype A to G specimens from two commercially available worldwide genotype panels. This assay has a dynamic range of at least 8 log,0 without the need for specimen dilution, good clinical intra- and interassay precision, and excellent correlation with the Bayer Diagnostics VERSANT HBV DNA 3.0 (branched DNA) assay (r = 0.93). Probit analysis determined the 95% detection level was 56 IU/ml, corresponding to 11 copies per PCR well. The high sensitivity, wide linear range, good reproducibility, and genotype inclusivity, combined with a small sample volume requirement and low cost, make this novel quantitative HBV real-time PCR assay particularly well suited for application to large clinical and epidemiological studies. C1 NCI, Viral Epidemiol Sect, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Ortiz-Conde, BA (reprint author), NCI, Viral Epidemiol Sect, AIDS Vaccine Program, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM conde@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 37 TC 26 Z9 28 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2006 VL 44 IS 9 BP 3325 EP 3333 DI 10.1128/JCM.00024-06 PG 9 WC Microbiology SC Microbiology GA 086YB UT WOS:000240708000041 PM 16954268 ER PT J AU Cornett, WR McCall, LM Petersen, RP Ross, MI Briele, HA Noyes, RD Sussman, JJ Kraybill, WG Iii, JMK Alexander, HR Lee, JE Mansfield, PF Pingpank, JF Winchester, DJ White, RL Chadaram, V Herndon, JE Fraker, DL Tyler, DS AF Cornett, Wendy R. McCall, Linda M. Petersen, Rebecca P. Ross, Merrick I. Briele, Henry A. Noyes, R. Dirk Sussman, Jeffrey J. Kraybill, William G. III, John M. Kane Alexander, H. Richard Lee, Jeffrey E. Mansfield, Paul F. Pingpank, James F. Winchester, David J. White, Richard L., Jr. Chadaram, Vijaya Herndon, James E., II Fraker, Douglas L. Tyler, Douglas S. TI Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group trial Z0020 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 58th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 03-06, 2005 CL Atlanta, GA SP Soc Surg Oncol ID TRANSIT MELANOMA METASTASES; ADVANCED MALIGNANT-MELANOMA; ALPHA TNF-ALPHA; GAMMA IFN-GAMMA; INTERFERON-GAMMA; PROGNOSTIC FACTORS; EXTREMITIES; CANCER; CHEMOTHERAPY AB Purpose To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. Patients and Methods Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. Results The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). Conclusion In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ Illinois, Chicago, IL USA. Evanston NW Healthcare, Evanston, IL USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Warren Grant Magnuson Clin Ctr, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RP Tyler, DS (reprint author), Duke Univ, Med Ctr, Box 3118, Durham, NC 27710 USA. EM tyler002@acpub.duke.edu FU NCI NIH HHS [U10 CA076001] NR 30 TC 121 Z9 124 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2006 VL 24 IS 25 BP 4196 EP 4201 DI 10.1200/JCO.2005.05.5152 PG 6 WC Oncology SC Oncology GA 081LV UT WOS:000240320000025 PM 16943537 ER PT J AU Siluk, D Oliveira, RV Rodriguez-Rosas, ME Ling, S Bos, A Ferrucci, L Wainer, IW AF Siluk, D. Oliveira, R. V. Rodriguez-Rosas, M. E. Ling, S. Bos, A. Ferrucci, L. Wainer, I. W. TI Application of an HPLC method to determine vitamin A and vitamin E isomers concentrations in human plasma SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 17-19, 2006 CL Cambridge, MA SP Amer Coll Clin Pharmacol C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Med Univ, Dept Biopharmaceut & Pharmacodynam, Gdansk, Poland. RI Oliveira, Regina/I-9547-2012 NR 0 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2006 VL 46 IS 9 MA 56 BP 1074 EP 1074 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078HE UT WOS:000240092500066 ER PT J AU Gupta, P Venitz, J Ramchandani, VA AF Gupta, Pankaj Venitz, J. rgen Ramchandani, Vijay A. TI In-vivo and in-vitro interspecies pharmacokinetic (PK) scaling for ethanol (EtOH) and propylene glycol (PG) SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 17-19, 2006 CL Cambridge, MA SP Amer Coll Clin Pharmacol C1 Virginia Commonwealth Univ, Richmond, VA USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2006 VL 46 IS 9 MA 97 BP 1084 EP 1084 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078HE UT WOS:000240092500106 ER PT J AU Hon, YY Sun, H Gonzalez, F Minneci, P Arai, A Gladwin, M AF Hon, Yuen Yi Sun, He Gonzalez, Felix Minneci, Peter Arai, Andrew Gladwin, Mark TI Population pharmacokinetics of sodium nitrite in dogs. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 17-19, 2006 CL Cambridge, MA SP Amer Coll Clin Pharmacol C1 NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Suntech Res Inst, Rockville, MD USA. Tasly Pharmaceut Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2006 VL 46 IS 9 MA 104 BP 1086 EP 1086 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 078HE UT WOS:000240092500113 ER PT J AU Metz, AE Fuemmeler, BF Brown, RT AF Metz, Arnold E. Fuemmeler, Bernard F. Brown, Ronald T. TI Implementation and assessment of an empirically validated intervention program to prevent tobacco use among African-American middle-school youth SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE prevention; tobacco; communication skills ID BEHAVIOR OUTCOMES; RISK-FACTORS; PROJECT; SMOKING; ADOLESCENT; CESSATION; HEALTH; TRIAL AB Evaluated Project Towards No Tobacco Use (TNT), a tobacco-use prevention program delivered in schools with primarily African-American students. Students were assigned randomly by classroom to either the intervention (n=58) or to a no-treatment control group (n=40). Students in the intervention group received a curriculum-based program over the course of 10 sessions. Pre-and post-assessments of tobacco knowledge, attitudes, communication, peer refusal, and smoking tendency were gathered. Students in the intervention group differed from their peers in the control group by evidencing greater knowledge and communication skills. We found this tobacco-use prevention program useful for African-American students. C1 Temple Univ, Coll Hlth Profess, Dept Publ Hlth, Philadelphia, PA 19140 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Temple Univ, Dept Psychol, Philadelphia, PA 19140 USA. Temple Univ, Dept Pediat, Philadelphia, PA 19140 USA. RP Brown, RT (reprint author), Temple Univ, Coll Hlth Profess, Dept Publ Hlth, 300 Jones Hall,3307 N Broad St, Philadelphia, PA 19140 USA. EM rtbrown@temple.edu NR 31 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD SEP PY 2006 VL 13 IS 3 BP 229 EP 238 DI 10.1007/s10880-006-9031-x PG 10 WC Psychology, Clinical SC Psychology GA 077UL UT WOS:000240056100003 ER PT J AU Taylor-Fishwick, DA Bowman, A Hamblet, N Bernard, P Harlan, DM Vinik, AI AF Taylor-Fishwick, David A. Bowman, Angela Hamblet, Natasha Bernard, Paul Harlan, David M. Vinik, Aaron I. TI Islet neogenesis associated protein transgenic mice are resistant to hyperglycernia induced by streptozotocin SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PANCREATIC-ISLETS; BETA-CELLS; POLY(ADP-RIBOSE) SYNTHETASE; IN-VIVO; INGAP; GENE; PENTADECAPEPTIDE; EXPRESSION; HAMSTERS; ENHANCER AB Islet neogenesis associated protein (INGAP) is a protein factor that can stimulate new islet mass from adult pancreatic progenitor cells. In models of islet neogenesis, INGAP expression is elevated in pancreatic acinar cells. Using a transgenic model to drive a sustained expression of INGAP in pancreatic acinar cells, we have identified a protection to chemical-induced hyperglycemia. A sustained expression of INGAP during development did not perturb islet development or basal blood glucose homeostasis, although beta-cell mass and pancreatic insulin content were significantly increased in the INGAP transgenic mice. When challenged with a diabetogenic dose of streptozotocin (STZ), mice carrying the INGAP transgene did not become hyperglycemic. In contrast, wild-type mice became and remained hyperglycemic, blood glucose > 550 mg/dl. The serum insulin levels and islet morphology were preserved in the transgenic mice after STZ treatment. These data suggest that the sustained expression of INGAP in the acinar pancreas confers resistance to a diabetogenic insult. The INGAP transgenic mouse provides a new model to uncover factors that are protective to diabetes onset and biomarkers to track beta-cell pathology. C1 Eastern Virginia Med Sch, Strelitz Diabet Res Inst, Dept Internal Med, Norfolk, VA 23510 USA. Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23510 USA. Eastern Virginia Med Sch, Dept Anat & Pathol, Norfolk, VA 23510 USA. NIDDK, DHHS, Mark O Hatfield Clin Res Ctr, NIH, Bethesda, MD 20892 USA. RP Taylor-Fishwick, DA (reprint author), Eastern Virginia Med Sch, Strelitz Diabet Res Inst, Dept Internal Med, Rm 215 Suite B,855 W Brambleton Ave, Norfolk, VA 23510 USA. EM taylord@evms.edu NR 42 TC 24 Z9 27 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 2006 VL 190 IS 3 BP 729 EP 737 DI 10.1677/joe.1.06698 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 095QY UT WOS:000241324000018 PM 17003274 ER PT J AU Shavers, VL Fagan, P Alexander, LAJ Clayton, R Doucet, J Baezconde-Garbanati, L AF Shavers, Vickie L. Fagan, Pebbles Jouridine Alexander, Linda A. Clayton, Richard Doucet, Jennifer Baezconde-Garbanati, Lourdes TI Workplace and home smoking restrictions and racial/ethnic variation in the prevalence and intensity of current cigarette smoking among women by poverty status, TUS-CPS 1998-1999 and 2001-2002 SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; RESTAURANT WORKERS; EXPOSURE; CONSUMPTION; OCCUPATION; HEALTH; ASTHMA; IMPACT; INCOME; BANS AB Study objective: Recognition of the health consequences of exposure to environmental tobacco smoke has led government agencies and many employers to establish policies that restrict cigarette smoking in public and workplaces. This cross sectional study examines the association of workplace smoking policies and home smoking restrictions with current smoking among women. Design: Participants were employed US women ages 18-64 who were self respondents to the 1998-1999 or 2000-2001 tobacco use supplement to the current population survey supplements. Cross tabulations and multivariate logistic regression analyses examine the association of selected demographic characteristics, occupation, income, workplace and home smoking policies/restrictions with current smoking, consumption patterns, and quit attempts among women by poverty level for five race/ethnic groups. Main results: The prevalence of either having an official workplace or home smoking policy that completely banned smoking increased with increased distance from the poverty level threshold. A complete ban on home smoking was more frequently reported by African American and Hispanic women although Hispanic women less frequently reported an official workplace smoking policy. In general, policies that permitted smoking in the work area or at home were associated with a higher prevalence of current smoking but this varied by poverty level and race/ethnicity. Home smoking policies that permitted smoking were associated with lower adjusted odds of having a least one quit attempt for nearly all poverty level categories but there was no association between having one quit attempt and workplace policies. Conclusion: Home smoking policies were more consistently associated with a lower prevalence of current smoking irrespective of poverty status or race/ethnicity than workplace policies. These findings underscore the importance of examining tobacco control policies in multiple domains (work and home) as well as by race/etknicity and socioeconomic position. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. Univ Kentucky, Coll Publ Hlth, Lexington, KY USA. Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. Univ So Calif, Keck Sch Med, Alhambra, CA USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, 6130 Execut Blvd,MSC-7344,EPN Room 4005, Bethesda, MD 20892 USA. EM shaversv@mail.nih.gov NR 37 TC 33 Z9 33 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD SEP PY 2006 VL 60 SU 2 BP 34 EP 43 DI 10.1136/jech.2006.046979 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 079VQ UT WOS:000240206400008 PM 17708009 ER PT J AU Heredia-Moya, J Hayakawa, Y Kirk, KL AF Heredia-Moya, Jorge Hayakawa, Yoshio Kirk, Kenneth L. TI Syntheses of 7-fluoro- and 6,7-difluoroserotonin and 7-fluoro- and 6,7-difluoromelatonin SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE serotonin; melatonin; Fischer indole synthesis ID SLEEP DISORDERS; HUMAN-PLATELETS; SEROTONIN; MELATONIN AB The Abramovitch adaption of the Fischer indole synthesis gave low yields of 7-fluoro-5-methoxytryptamine due in part to decomposition during the required decarboxylation step. Therefore, 7-fluoro- and 6,7-difluoro-5-methoxytryptamines were prepared by reaction of aminobutyr-aldehyde (generated in situ from the diethyl acetal) with 2-fluoro- and 2,3-difluoro-4-methoxyphenylhydrazine, and the products converted to the corresponding serotonins. The melatonins were prepared by a one-pot reaction that involved in situ acetylation of the ammobutyraldehyde. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM kennethk@intra.niddk.nih.gov NR 17 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD SEP PY 2006 VL 127 IS 9 BP 1256 EP 1260 DI 10.1016/j.jfluchem.2006.06.015 PG 5 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 089KQ UT WOS:000240879900015 ER PT J AU Schwilke, EW dos Santos, MIS Logan, BK AF Schwilke, Eugene W. Sampaio dos Santos, Maria Isabel Logan, Barry K. TI Changing patterns of drug and alcohol use in fatally injured drivers in Washington State SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; toxicology; drug impaired driving; demographics ID DRIVING IMPAIRMENT; TRAFFIC ACCIDENTS; METHAMPHETAMINE; PERFORMANCE; CRASHES; PREVALENCE; MARIJUANA; SMOKING; SPAIN; MDMA AB We have previously reported on patterns of drug and alcohol use in fatally injured drivers in Washington State. Here we revisit that population to examine how drug use patterns have changed in the intervening 9 years. Blood and serum specimens from drivers who died within 4 h of a traffic accident between February 1, 2001, and January 31, 2002, were analyzed for illicit and therapeutic drugs and alcohol. Drugs when present were quantitated. Samples suitable for testing were obtained from 370 fatally injured drivers. Alcohol was detected above 0.01 g/100 mL in 41% of cases. The mean alcohol concentration for those cases was 0.17 g/100 mL (range 0.02-0.39 g/100 mL). Central nervous system (CNS) active drugs were detected in 144 (39%) cases. CNS depressants including carisoprodol, diazepam, hydrocodone, diphenhydramine, amitriptyline, and others were detected in 52 cases (14.1%), cannabinoids were detected in 47 cases (12.7%), CNS stimulants (cocaine and amphetamines) were detected in 36 cases (9.7%), and narcotic analgesics (excluding morphine which is often administered iatrogenically in trauma cases) were detected in 12 cases (3.2%). For those cases which tested positive for alcohol c. 40% had other drugs present which have the potential to cause or contribute to the driver's impairment. Our report also considers the blood drug concentrations in the context of their interpretability with respect to driving impairment. The data reveal that over the past decade, while alcohol use has declined, some drug use, notably methamphetamine, has increased significantly (from 1.89% to 4.86% of fatally injured drivers) between 1992 and 2002. Combined drug and alcohol use is a very significant pattern in this population and is probably overlooked in DUI enforcement programs. C1 Washington State Toxicol Lab, Forens Lab Serv Bur, Seattle, WA 98134 USA. Natl Inst Drug Abuse, Baltimore, MD 21224 USA. Univ Fed Rio de Janeiro, Fac Farm, Dept Prod Nat Alimentos, BR-21941591 Rio De Janeiro, Brazil. RP Logan, BK (reprint author), Washington State Toxicol Lab, Forens Lab Serv Bur, Washington State Patrol,2203 Airport Way S, Seattle, WA 98134 USA. EM barry.logan@wsp.wa.gov NR 31 TC 47 Z9 47 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 2006 VL 51 IS 5 BP 1191 EP 1198 DI 10.1111/j.1556-4029.2006.00239.x PG 8 WC Medicine, Legal SC Legal Medicine GA 087WO UT WOS:000240773700039 PM 17018108 ER PT J AU Thorsen, F Afione, S Huszthy, PC Tysnes, BB Svendsen, A Bjerkvig, R Kotin, RM Lonning, PE Hoover, F AF Thorsen, Frits Afione, Sandra Huszthy, Peter C. Tysnes, Berit B. Svendsen, Agnete Bjerkvig, Rolf Kotin, Robert M. Lonning, Per Eystein Hoover, Frank TI Adeno-associated virus (AAV) serotypes 2, 4 and 5 display similar transduction profiles and penetrate solid tumor tissue in models of human glioma SO JOURNAL OF GENE MEDICINE LA English DT Article DE gene therapy; glioblastoma multiforme; viral transduction; tumor spheroids; AAV2; AAV4; AAV5 ID CENTRAL-NERVOUS-SYSTEM; GENE-THERAPY; VIRAL VECTORS; SIALIC-ACID; IN-VIVO; MALIGNANT GLIOMAS; LIMITED EFFICACY; HEMOPHILIA-B; HUMAN BRAIN; RAT-BRAIN AB Background Adeno-associated viral (AAV) vectors are potent delivery vehicles for gene transfer strategies. directed at the central nervous system (CNS), muscle and liver. However, comparatively few studies have described AAV-mediated gene transfer to tumor tissues. We have previously demonstrated that while AAV2 and Adenoviral (Ad) 5 vectors have similar broad host ranges in tumor-derived cell lines, AAV2 was able to penetrate human glioblastoma biopsy spheroids and xenografts more efficiently than Ad 5 vectors. These results suggested that AAV vectors could be suitable for therapeutic gene delivery to solid tumor tissue. In the present work, the transduction efficacy of AAV serotypes 4 and 5 were compared to AAV2, both in vitro and in intracranial GBM xenografts derived from patient biopsies implanted into nude rats. Methods AAV vector serotypes 2, 4, and 5 containing either the green fluorescent protein (GFP) or the bacterial beta-galactosidase (lacZ) reporter gene were added to five different human glioma cell lines, to multicellular spheroids generated from glioblastoma patient biopsies, and to spheroids xenografted intracranially in nude rats. Transduction efficiency was assessed by fluorescence imaging, histochemistry, immunohistochemistry and flow cytometry. Results While all three AAV serotypes were able to transduce the glioma cell lines when added individually or when they were administered in concert, AAV2 transduced the glioma cells most effectively compared to AAV4 or AAV5. Upon infecting glioblastoma spheroids in vitro, all three AAV serotypes efficiently transduced cells located at the surface as well as within deeper layers of the spheroids. In addition, similarly to what was observed for AAV2 [16], both AAV4 and AAV5 were able to transduce human glioblastoma xenografts implanted intracranially. Conclusions In addition to the widely used AAV2 serotype, AAV4 and AAV5 serotypes may also be used to transduce biologically diverse glioma cell lines. They also penetrate and transduce solid human tumor tissue derived from patient biopsies. Therefore, the data presented here provide a proof of principle for developing AAV4 and AAV5 as treatment vehicles for human malignant gliomas. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Univ Bergen, Dept Biomed, Sect Anat & Cell Biol, N-5009 Bergen, Norway. Haukeland Univ Hosp, Dept Oncol & Med Phys, N-5021 Bergen, Norway. NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. Univ Bergen, Haukeland Univ Hosp, Dept Internal Med, Sect Oncol, N-5009 Bergen, Norway. Univ Bergen, Haukeland Univ Hosp, Hosp Program Genet Therapy, N-5009 Bergen, Norway. Ctr Rech Publ, Luxembourg, Luxembourg. Univ Bergen, Dept Biomed, NorLux Neurooncol, N-5020 Bergen, Norway. RP Thorsen, F (reprint author), Univ Bergen, Dept Biomed, Sect Anat & Cell Biol, Jonas Lies Vei 91, N-5009 Bergen, Norway. EM frits.thorsen@biomed.uib.no RI kotin, robert/B-8954-2008; Huszthy, Peter Csaba/H-1414-2016 OI Huszthy, Peter Csaba/0000-0003-0184-8989 FU Intramural NIH HHS NR 61 TC 16 Z9 21 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP PY 2006 VL 8 IS 9 BP 1131 EP 1140 DI 10.1002/jgm.939 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 093MN UT WOS:000241172500006 PM 16810631 ER PT J AU Sunderland, T AF Sunderland, Trey TI Modern diagnostic approaches in dementia: On the cusp of change SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Editorial Material C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2006 VL 19 IS 3 BP 123 EP 124 DI 10.1177/0891988706291077 PG 2 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 077HW UT WOS:000240020900001 PM 16880352 ER PT J AU Sunderland, T Hampel, H Takeda, M Putnam, KT Cohen, RM AF Sunderland, Trey Hampel, Harald Takeda, Masatoshi Putnam, Karen T. Cohen, Robert M. TI Biomarkers in the diagnosis of Alzheimer's disease: Are we ready? SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT Meeting on Diagnostic Issues in Dementia - Future of Psychiatric Diagnosis - Refinding the Research Agenda CY SEP 15-17, 2005 CL Geneva, SWITZERLAND SP Amer Psychiat Assoc, US Natl Inst Hlth, World Hlth Org DE biomarkers; Alzheimer's disease; cerebrospinal fluid; sensitivity and specificity; diagnosis ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID-TAU; APOLIPOPROTEIN-E GENOTYPE; CSF PHOSPHORYLATED TAU; TEMPORAL-LOBE ATROPHY; DIFFERENTIAL-DIAGNOSIS; CLINICAL-DIAGNOSIS; NATIONAL-INSTITUTE; BIOLOGICAL MARKERS; LUMBAR PUNCTURE AB Although clinical manifestations of cognitive dysfunction and impairments of activities of daily living are the current standard measures for the diagnosis of Alzheimer's disease, biomarkers are receiving increasing attention in research centers as possible early diagnostic measures or as surrogate measures of the ongoing pathology. In preparation for the upcoming development of the Diagnostic and Statistical Manual of Mental Disorders (5th ed; DSM-V) nosology, the American Psychiatric Association has sponsored an effort to reassess the current approaches to diagnosis in dementia in general and Alzheimer's disease in particular. This article focuses on the potential use of biomarkers in the diagnosis of Alzheimer's disease, in the monitoring of mild cognitive impairment, and as possible prognostic markers in normal controls at risk for dementia. Most advanced information is available with the biomarkers found in the cerebrospinal. fluid, but there are many other potential biomarkers using blood, brain imaging, or a combination. The current biomarker approaches to diagnosis are reviewed along with a special emphasis on near-term recommendations and further research directions. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Univ Munich, Dept Psychiat, Munich, Germany. Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka, Japan. N Shore LIJ Hlth Syst, Litwin Zucker Res Ctr, New York, NY USA. Cedars Sinai Med Ctr, Dept Psychiat, Los Angeles, CA 90048 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, CRC Bldg,Room 2-5360, Bethesda, MD 20892 USA. EM trey@mail.nih.gov FU NIMH NIH HHS [Z01 MH00330-14] NR 85 TC 39 Z9 41 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SEP PY 2006 VL 19 IS 3 BP 172 EP 179 DI 10.1177/0891988706291088 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 077HW UT WOS:000240020900008 PM 16880359 ER PT J AU Li, DS An, D Zhou, YS Liu, J Waalkes, MP AF Li, Dasheng An, Dong Zhou, Yunsu Liu, Jie Waalkes, Michael P. TI Current status and prevention strategy for coal-arsenic poisoning in Guizhou, China SO JOURNAL OF HEALTH POPULATION AND NUTRITION LA English DT Review DE arsenic; arsenicosis; coal-arsenic exposure; health effects; neoplasms; health education; nutrition; drug therapy; review literature; China ID CONTAMINATION; BANGLADESH AB Arsenic exposure from burning coal with high arsenic contents occurs in southwest Guizhou, China. Coal in this region contains extremely high concentrations of inorganic arsenic. Arsenic exposure from coal-burning is much higher than exposure from arsenic-contaminated water in other areas of China. The current status and prevention strategies for arsenic poisoning from burning high-arsenic coal in southwest Guizhou, China, is reported here. Over 3,000 arsenic-intoxicated patients were diagnosed based on skin lesions and urinary arsenic excretion. Non-cancerous toxicities and malignancies were much more common and severe in these patients than in other arsenic-affected populations around the world. The high incidence of cancer and arsenic-related mortality in this cohort is alarming. Chelation therapy was performed but the long-term therapeutic effects are not satisfactory. The best prevention strategy is to eliminate arsenic exposure. Funds from the Chinese Government are currently available to solve this arsenic exposure problem. Strategies include the installation of vented stoves, the use of marsh gas to replace coal, health education, the improvement of nutritional status, and the use of various therapies to treat arsenic-induced skin and liver diseases. C1 Ctr Dis Control Guizhou, Guiyang 550004, Peoples R China. NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC USA. RP Li, DS (reprint author), Ctr Dis Control Guizhou, 73 Ba Ge Yan Rd, Guiyang 550004, Peoples R China. EM cdcdbs@gzcdc.gov.cn FU Intramural NIH HHS NR 14 TC 8 Z9 8 U1 2 U2 18 PU I C D D R B-CENTRE HEALTH POPULATION RESEARCH PI DHAKA PA MOHAKHALI, 1212 DHAKA, BANGLADESH SN 1606-0997 J9 J HEALTH POPUL NUTR JI J. Heatlh Popul. Nutr. PD SEP PY 2006 VL 24 IS 3 BP 273 EP 276 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 148RE UT WOS:000245091500004 PM 17366768 ER PT J AU Bellizzi, KM Blank, TO Oakes, CE AF Bellizzi, Keith M. Blank, Thomas O. Oakes, Claudia E. TI Social comparison frocessesin autobiographies of adult cancer survivors SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Article DE cancer; free narratives; social comparison ID DOWNWARD EVALUATION; BREAST-CANCER; ADJUSTMENT; THREAT AB Cancer survivors often compare their situations to other survivors' situations. However, types of social comparison processes used and resulting outcomes are not clearly delineated. This study explores usage and consequences of three social comparison styles (downward, upward and parallel) of adult cancer survivors in free narratives, using content analysis of 30 autobiographical books by survivors ranging in age from 30-70 (M = 54, SD = 10.04); 43 percent prostate cancer, 17 percent breast cancer and 40 percent other cancers. Overall, cancer survivors used more parallel comparisons than directional comparisons, followed by upward comparisons. Each type of comparison was associated with different kinds of positive and negative consequences. C1 Univ Connecticut, Sch Family Studies, Storrs, CT 06269 USA. NCI, Bethesda, MD 20892 USA. RP Blank, TO (reprint author), Univ Connecticut, Sch Family Studies, Storrs, CT 06269 USA. EM thomas.blank@uconn.edu FU NIA NIH HHS [R03AG17728] NR 32 TC 17 Z9 17 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD SEP PY 2006 VL 11 IS 5 BP 777 EP 786 DI 10.1177/1359105306066637 PG 10 WC Psychology, Clinical SC Psychology GA 087VR UT WOS:000240771400010 PM 16908472 ER PT J AU Davis, LM Pei, ZT Trush, MA Cheskin, LJ Contoreggi, C McCullough, K Watkins, PA Moran, TH AF Davis, Lisa M. Pei, Zhengtong Trush, Michael A. Cheskin, Lawrence J. Contoreggi, Carlo McCullough, Karen Watkins, Paul A. Moran, Timothy H. TI Bromocriptine reduces steatosis in obese rodent models SO JOURNAL OF HEPATOLOGY LA English DT Article DE bromocriptine; dopamine D2 agonist; obesity; nonalcoholic fatty liver disease; NAFLD ID BODY-FAT STORES; MESOCRICETUS-AURATUS; GLUCOSE-TOLERANCE; OXIDATIVE STRESS; ZUCKER RATS; DOPAMINE; WEIGHT; INSULIN; REWARD; MICE AB Background/Aims: Obesity is a risk factor for glucose intolerance, steatosis, and oxidative stress, characteristics of nonalcoholic fatty liver disease. Bromocriptine may have anti-obesity, insulin-sensitizing, lipolytic, and antioxidant properties. We, therefore, hypothesized that bromocriptine would improve markers of nonalcoholic fatty liver disease in obese rodent models. Methods: We performed a randomized, controlled experiment in genetically obese fatty Zucker rats and diet-induced obese rats to assess for behavioral and peripheral anti-obesity actions of bromocriptine (10 mg/kg) that would improve nonalcoholic fatty liver disease. Results: Behaviorally, food intake decreased and locomotor activity increased in bromocriptine-treated fatty Zucker and dietary-induced obese rats. Peripherally, liver triglycerides were significantly reduced and hepatic manganese superoxide dismutase significantly increased in bromocriptine-treat, d fatty Zucker and diet-induced obese rats compared to controls. Blood glucose was significantly lower in bromocriptine-treated Zucker rats compared to fatty controls and was no different than that of lean controls. Conclusions: Improvements in obesigenic behaviors, glucose tolerance, hepatic lipid accumulation, and mitochondrial oxidative stress observed in genetically obese and diet-induced obese rodents indicate that bromocriptine may be promising as a broad-based therapy for nonalcoholic fatty liver disease. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD 21205 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Davis, LM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Human Nutr, Baltimore, MD 21205 USA. EM ldavismc@jhsph.edu FU Intramural NIH HHS; NIDDK NIH HHS [DK19302] NR 33 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2006 VL 45 IS 3 BP 439 EP 444 DI 10.1016/j.jhep.2006.03.019 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 084KF UT WOS:000240531100015 PM 16780999 ER PT J AU Fernandez-Manjarres, JF Idol, J Sork, VL AF Fernandez-Manjarres, Juan F. Idol, Jacquelyn Sork, Victoria L. TI Mating patterns of black oak Quercus velutina (Fagaceae) in a Missouri oak-hickory forest SO JOURNAL OF HEREDITY LA English DT Article ID POLLEN FLOW; 2-GENERATION ANALYSIS; HETEROGENEITY; DISPERSAL; POPULATIONS; LANDSCAPE; DISTANCE; POOL AB Wind-pollinated forest trees usually have high outcrossing rates, but allogamy does not necessarily translate into high pollen movement. The goal of this study was to determine the outcrossing rates, pollen pool genetic structure, and the size of the effective pollination neighborhood in a population of black oak, Quercus velutina, in a Missouri oak-hickory forest. Based on 6 allozyme loci, 12 maternal trees, and 439 progenies sampled along a transect of 1300 m, we found complete outcrossing (t(m) = 1.000, P < 0.001) and small amounts of biparental inbreeding. Using a TwoGener analysis of the pollen gene pool, we found significant structure across maternal plants (Phi(FT) = 0.078, P < 0.001), which when corrected for adult inbreeding translates into Phi(FT) = 0.066 that corresponds to an effective number of pollen donors of 7.5 individuals. Assuming a bivariate normal distribution and an adult density of 16.25 trees ha(-1), we estimated that the effective pollination neighborhood area had a radius of 41.9 m. Even assuming that our estimates may be conservative, these findings join a growing body of evidence that suggest that the local neighborhood of wind-pollinated forest tree populations may be relatively small creating opportunities for local selection and genetic drift. C1 Univ Paris 11, Lab Ecol Systemat & Evolut, F-91405 Orsay, France. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. RP Fernandez-Manjarres, JF (reprint author), Univ Paris 11, Lab Ecol Systemat & Evolut, Bat 360, F-91405 Orsay, France. EM juan.fernandez@ese.u-psud.fr NR 23 TC 14 Z9 14 U1 1 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 2006 VL 97 IS 5 BP 451 EP 455 DI 10.1093/jhered/es1022 PG 5 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 101QS UT WOS:000241756100005 PM 16985080 ER PT J AU Mehta, S Pavana, RK Yogeeswari, P Sriram, D Stables, J AF Mehta, Shalini Pavana, Roheeth Kumar Yogeeswari, Perumal Sriram, Dharmarajan Stables, James TI Heteroaryl-substuted semicarbazones: synthesis and anticonvulsant activity of N-(3-methylpyridin-2-yl)-substituted semicarbazones SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID ANTIEPILEPTIC DRUG DEVELOPMENT; ARYL SEMICARBAZONES AB A series of substituted N-(3-methylpyridin-2-yl) semicarbazones was designed and synthesized to meet the structural requirements essential for anticonvulsant activity. The structures of all the synthesized compounds were confirmed by means of spectral and elemental analysis. All the compounds were evaluated for their anticonvulsant activity by maximal electroshock seizures (MES) test, subcutaneous pentylenetetrazole (scPTZ) screen, subcutaneous strychnine (scSTY) pattern test and subcutaneous picrotoxin (scPIC) seizure threshold test along with the behavioral, and neurotoxicity evaluation. A number of N-(3-methylpyridin-2-yl) semicarbazone derivatives exhibited significant protection after intraperitoneal administration at the dose of 100 and 300 mg/kg. Compound N-1-(3-methylpyridin-2-yl)-N-4-(isatin) semicarbazone (19) emerged as the most active analogue of the series, being more effective in most of the test models than ethosuximide and sodium valporate. C1 Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. RI Pavana, Roheeth/F-5839-2017 OI Pavana, Roheeth/0000-0001-6256-3683 NR 27 TC 1 Z9 1 U1 0 U2 1 PU HETERO CORPORATION PI PROVO PA PO BOX 170, PROVO, UT 84603-0170 USA SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD SEP-OCT PY 2006 VL 43 IS 5 BP 1287 EP 1293 PG 7 WC Chemistry, Organic SC Chemistry GA 098SA UT WOS:000241541900022 ER PT J AU Chen, J Fujimoto, C Vistica, BP Wawrousek, EF Kelsall, B Gery, I AF Chen, Jun Fujimoto, Chiaki Vistica, Barbara P. Wawrousek, Eric F. Kelsall, Brian Gery, Igal TI Active participation of antigen-nonspecific lymphoid cells in immune-mediated inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; DENDRITIC CELLS; T-CELLS; OCULAR INFLAMMATION; DOWN-REGULATION; DISEASE; LYMPHOCYTES; INDUCTION; EXTRAVASATION; RECRUITMENT AB The pathogenic process of tissue-specific autoimmune disease depends to a large extent on recruitment of Ag-nonspecific cells into the target tissue. Little is known, however, about the recruitment process and the features that characterize the recruited cells. In this study, we analyzed the recruitment of Ag-nonspecific lymphoid cells into an inflammatory site by using an experimental system in which TCR-transgenic Th1 cells are adoptively transferred to induce ocular inflammation in recipient mice that express the target Ag in their eyes. A sharp increase in number of all host cell populations was observed in the recipient spleen, reaching a peak on day 4 postcell transfer and declining thereafter. A large portion of the host's spleen CD4 cells underwent phenotypic changes that facilitate their migration into the target organ, the eye. These changes included increased expression of the chemokine receptor CXCR3, and the adhesion molecule CD49d, as well as a decline in expression of CD62L. The host lymphocytes migrated into the recipient mouse eye more slowly than the donor cells, but became the great majority of the infiltrating cells at the peak of inflammation on day 7 postcell injection. Interestingly, the mass migration of host T cells was preceded by an influx of host dendritic cells, that reached their peak on day 4 postcell injection. The eye-infiltrating host CD4 lymphocytes underwent additional changes, acquiring a profile of activated lymphocytes, i.e., up-regulation of CD25 and CD69. Our results thus provide new information about the active participation of Ag-nonspecific lymphoid cells in immune-mediated inflammation. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov RI Wawrousek, Eric/A-4547-2008 FU Intramural NIH HHS NR 26 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2006 VL 177 IS 5 BP 3362 EP 3368 PG 7 WC Immunology SC Immunology GA 077BN UT WOS:000240002800073 PM 16920977 ER PT J AU Maloney, EM Yamano, Y VanVeldhuisen, PC Sawada, T Kim, N Cranston, B Hanchard, B Jacobson, S Hisada, M AF Maloney, Elizabeth Margaret Yamano, Yoshihisa VanVeldhuisen, Paul C. Sawada, Takashi Kim, Norma Cranston, Beverley Hanchard, Barrie Jacobson, Steven Hisada, Michie TI Natural history of viral markers in children infected with human T lymphotropic virus type I in Jamaica SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; HTLV-I; CELL LEUKEMIA; PLACENTAL-TRANSFER; PRETERM INFANTS; PROVIRAL LOAD; FULL-TERM; DERMATITIS; ANTIBODIES; CARRIERS AB Purpose. We conducted a longitudinal analysis of human T lymphotropic virus type I (HTLV-I) viral markers in 28 Jamaican mothers and their children, who were monitored for a median of 6.2 years after the birth of the children. Methods. The HTLV-I provirus DNA load was measured using the Taqman system (PE Applied Biosystems). The HTLV-I antibody titer was determined using the Vironstika HTLV-I/II Microelisa System (Organon Teknika). The HTLV-I Tax-specific antibody titers were measured using an enzyme-linked immunosorbent assay. Generalized estimating equations were used to describe the associations of exposure variables with sequentially measured levels of HTLV-I viral markers in children. Results. The HTLV-I antibody titer increased significantly up to 1 year after infection, reaching equilibrium at a median titer of 1:7786. The prevalence of Tax-specific antibody reached 80% at 2 years after infection. The provirus load increased up to 2 years after infection, reaching equilibrium at a median of 6695 copies/100,000 peripheral blood mononuclear cells. The increase in the provirus load was significant only among children with eczema, but not among children without eczema. Conclusions. The provirus loads in children increased for an additional year after their antibody titers had stabilized, possibly as a result of the expansion of HTLV-I-infected clones. This effect was significant only for children with eczema. Among HTLV-I-infected children, eczema may be a cutaneous marker of the risk of HTLVI-associated diseases developing in adulthood. C1 Ctr Dis Control & Prevent, Viral Exanthems & Herpesvirus Branch, Div Viral & Rickettsial Dis, Nat Ctr Infect Dis,Dept Hlth & Human Serv, Atlanta, GA 30333 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Dept Hlth & Human Derv, Bethesda, MD USA. EMMES Corp, Rockville, MD USA. Res Triangle Inst, Rockville, MD USA. Kagoshima City Hosp, Kagoshima, Japan. Clin Res Ctr, Depp Clin Res & Dev, Eisai, Tokyo, Japan. Univ W Indies, Mona Kingston, Jamaica. RP Maloney, EM (reprint author), Ctr Dis Control & Prevent, Viral Exanthems & Herpesvirus Branch, Div Viral & Rickettsial Dis, Nat Ctr Infect Dis,Dept Hlth & Human Serv, 1600 Clifton Rd,MS A-15, Atlanta, GA 30333 USA. EM evm3@cdc.gov FU NCI NIH HHS [N01-CP33043-21, N01-CP31006, N01-CP-40548, N01-CP-21121] NR 35 TC 8 Z9 8 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2006 VL 194 IS 5 BP 552 EP 560 DI 10.1086/506365 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 078HH UT WOS:000240092800004 PM 16897651 ER PT J AU Jacobson, JM Bucy, RP Spritzler, J Saag, MS Eron, JJ Coombs, RW Wang, R Fox, L Johnson, VA Cu-Uvin, S Cohn, SE Mildvan, D O'Neill, D Janik, J Purdue, L O'Connor, DK Di Vita, C Frank, I AF Jacobson, Jeffrey M. Bucy, R. Pat Spritzler, John Saag, Michael S. Eron, Joseph J., Jr. Coombs, Robert W. Wang, Rui Fox, Lawrence Johnson, Victoria A. Cu-Uvin, Susan Cohn, Susan E. Mildvan, Donna O'Neill, Dorothy Janik, Jennifer Purdue, Lynette O'Connor, Deborah K. Di Vita, Christine Frank, Ian CA Natl Inst Allergy Infectious AIDS Clinical Trials Grp TI Evidence that intermittent structured treatment interruption, but not immunization with ALVAC-HIV vCP 1452, promotes host control of HIV replication: The results of AIDS Clinical Trials Group 5068 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT AIDS Vaccine 2005 Conference CY SEP, 2005 CL Montreal, CANADA ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CLASS-I MOLECULES; CANARYPOX VACCINE; IMMUNE-RESPONSES; GENOTYPING KIT; INFECTION; COMBINATION; PROTEIN; DISCONTINUATION AB Background. The ability to control human immunodeficiency virus (HIV) replication in vivo in the absence of antiretroviral therapy (ART) is a measure of the efficiency of antiviral immunity. In a study of patients with chronic, ART-suppressed HIV infection, AIDS Clinical Trials Group 5068 investigated the effects of immunization with an exogenous HIV vaccine and pulse exposure to the subject's unique viral epitopes, by means of structured treatment interruptions (STIs), on the dynamics of viral rebound during a subsequent analytical treatment interruption (ATI). Methods. Ninety-seven subjects receiving stable ART with an HIV-1 RNA load < 50 copies/mL and CD4+ T lymphocyte count > 400 cells/mm(3) were randomized to undergo continued ART, STIs, ALVAC-HIV vCP1452 immunization, or STIs and ALVAC-HIV vCP1452 immunization. Results. Subjects in the 2 STI arms had a significantly longer median doubling time in the period of the initial rise of viral load, a significantly lower median peak viral load, a significantly lower median end-of-ATI viral load set point, and a greater proportion of subjects with an end-of-ATI viral load set point < 1000 copies/mL, compared with the subjects in the 2 arms without STIs. With an immunization schedule of 3 sets of 3 weekly injections, ALVAC-HIV vCP1452 did not affect viral load measures. Conclusions. In this randomized, controlled study of intermittent STI as a therapeutic autoimmunization strategy, evidence of enhanced immunologic control of HIV replication was demonstrated. C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, New York, NY 10003 USA. Albert Einstein Coll Med, New York, NY USA. Univ Rochester, Rochester, NY USA. Frontier Sci, Amherst, NY USA. Univ Alabama, Tuscaloosa, AL 35487 USA. Birmingham Veterans Adm Med Ctr, Birmingham, AL USA. Harvard Sch Publ Hlth, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Univ Washington, Seattle, WA 98195 USA. NIAID, Bethesda, MD 20892 USA. Social & Sci Syst, Silver Spring, MD USA. Brown Univ, Providence, RI 02912 USA. Indiana Univ, Indianapolis, IN 46204 USA. Sanofe Pasteur, Lyon, France. Univ Penn, Philadelphia, PA USA. RP Jacobson, JM (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 1st Ave 16th St,19BH14, New York, NY 10003 USA. EM jjacobson@chpnet.org FU NCRR NIH HHS [RR00096, RR00046, RR00044, RR00040, RR00032]; NIAID NIH HHS [AI25868, AI32783, AI27664, AI25903, AI25879, AI38855, U01AI38858, P30 AI27767, AI50410, AI46381, AI46370, AI38858, AI27665, AI27658, AI25924] NR 32 TC 46 Z9 47 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2006 VL 194 IS 5 BP 623 EP 632 DI 10.1086/506364 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 078HH UT WOS:000240092800014 PM 16897661 ER PT J AU Affara, NI Schanbacher, BL Pei, P Mallery, SR Trempus, CS Bauer, JA Robertson, FM AF Affara, Nesrine I. Schanbacher, Brandon L. Pei, Ping Mallery, Susan R. Trempus, Carol S. Bauer, John A. Robertson, Fredika M. TI Similarities of akt activation in cutaneous wound repair and skin carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Meeting Abstract C1 [Affara, Nesrine I.; Robertson, Fredika M.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Schanbacher, Brandon L.] Columbus Childrens Res Inst, Ctr Cardiovasc Pharmacol, Columbus, OH USA. [Pei, Ping; Mallery, Susan R.] Ohio State Univ, Dept Oral & Maxillofacial Surg Oral Pathol & Peri, Columbus, OH 43210 USA. [Trempus, Carol S.] Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD SEP PY 2006 VL 11 IS 1 BP 142 EP 142 PG 1 WC Dermatology SC Dermatology GA 265JV UT WOS:000253355800021 ER PT J AU Grady, C Horstmann, E Sussman, JS Hull, SC AF Grady, Christine Horstmann, Elizabeth Sussman, Jefftey S. Hull, Sara Chandros TI The limits of disclosure: What research subjects want to know about investigator financial interests SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID CONFLICTS-OF-INTEREST; BIOMEDICAL-RESEARCH; INDUSTRY; FACULTY AB Research participants' views about investigator financial interests were explored. Reactions ranged from concern to acceptance, indifference, and even encouragement. Although most wanted such information, some said it did not matter, was private, or was burdensome, and other factors were more important to research decisions. Very few said it would affect their research decisions, and many assumed that institutions managed potential conflicts of interest. Although disclosure of investigator financial interest information to research participants is often recommended, its usefulness is limited, especially when participation is desired because of illness. C1 NIH, Sect Human Subjects Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. NIH, Off Evaluat, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Sect Human Subjects Res, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. NR 25 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 2006 VL 34 IS 3 BP 592 EP + DI 10.1111/j.1748-720X.2006.00073.x PG 9 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 080EM UT WOS:000240230700016 PM 17144183 ER PT J AU Resnik, DB AF Resnik, David B. TI Compensation for research-related injuries - Ethical and legal issues SO JOURNAL OF LEGAL MEDICINE LA English DT Article ID LITIGATION; LIABILITY; BOARDS 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 NR 50 TC 16 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0194-7648 J9 J LEGAL MED JI J. Legal Med. PD SEP PY 2006 VL 27 IS 3 BP 263 EP 287 DI 10.1080/01947640600870866 PG 25 WC Law; Social Sciences, Biomedical SC Government & Law; Biomedical Social Sciences GA 081YD UT WOS:000240352600001 PM 16959652 ER PT J AU Rosenberg, HF Griebel, P AF Rosenberg, Helene F. Griebel, Philip TI Interview with Dr. Philip Griebel regarding Pivotal Advance: Passively acquired membrane proteins alter the functional capacity of bovine polymorphonuclear cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2006 VL 80 IS 3 BP 479 EP 480 DI 10.1096/jlb.1306078 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MF UT WOS:000243015700004 ER PT J AU Takase, H Yu, CR Ham, DI Chan, CC Chen, J Vistica, BP Wawrousek, EF Durum, SK Egwuagu, CE Gery, I AF Takase, Hiroshi Yu, Cheng-Rong Ham, Don-Il Chan, Chi-Chao Chen, Jun Vistica, Barbara P. Wawrousek, Eric F. Durum, Scott K. Egwuagu, Charles E. Gery, Igal TI Inflammatory processes triggered by TCR engagement or by local cytokine expression: differences in profiles of gene expression and infiltrating cell populations SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE immune-mediated inflammation; eye; experimental autoimmune uveitis (EAU); transgenic mice ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; IL-1-ALPHA TRANSGENIC MICE; IFN-GAMMA; IMMUNE PATHOLOGY; LENS; CHEMOKINES; INDUCTION; APOPTOSIS; ENDOTOXIN; DISEASE AB Immune cell-mediated inflammatory responses are triggered by TCR engagement with the target antigen, the initial event that brings about the complex sequence of events of the inflammatory process. Another form of inflammation is induced by local expression of certain cytokines. Unlike the former form of inflammation, little is known about the basic features of the cytokine-induced responses. Here, we analyzed tissue morphology, the infiltrating cells, and up-regulated, inflammation-related genes in mouse eyes in which inflammation is triggered by local transgenic (Tg) expression of cytokines and compared these features with those in eyes with experimental autoimmune uveitis (EAU), in which inflammation is initiated by engagement of TCR on sensitized T cells with their target antigen, followed by the well-defined, subsequent cytokine production. Eyes of IFN-gamma Tg mice exhibited severe, morphological changes but essentially no inflammation, and intense inflammation was found in eyes of interleukin (IL)- or IL-7 Tg mice. The cellular infiltration in eyes of these latter two lines of Tg mice resembled that in eyes with EAU by including many CD4 cells, but unlike in EAU, the infiltration in Tg eyes contained large proportions of B cells and only small numbers of macrophages. Real-time PCR analysis of eye RNA revealed differences among the disease models in the expression profiles of various inflammation-related genes. It is interesting that a bias toward T helper cell type I immunity (high IFN-gamma, RANTES/CCL5, MIG/CXCL9, and T-bet but low IL-4, IL-5, and GATA-3 transcripts) was found in EAU eyes but not in eyes of IL- and IL-7 Tg mice. The results thus show that similar to TCR engagement, local expression of certain cytokines triggers a complex, subsequent production of numerous inflammation-related molecules, but features of the ensued inflammatory process are determined by the triggering mechanism. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21701 USA. Tokyo Med & Dent Univ, Dept Ophthalmol & Visual Sci, Grad Sch, Tokyo, Japan. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N208,10 Ctr Dr, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov RI Wawrousek, Eric/A-4547-2008 FU Intramural NIH HHS NR 26 TC 9 Z9 9 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2006 VL 80 IS 3 BP 538 EP 545 DI 10.1189/jlb.1205719 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MF UT WOS:000243015700011 PM 16793919 ER PT J AU Pessach, I Shmelzer, Z Leto, TL Dinauer, MC Levy, R AF Pessach, Itai Shmelzer, Zeev Leto, Thomas L. Dinauer, Mary C. Levy, Rachel TI The C-terminal flavin domain of gp91(phox) bound to plasma membranes of granulocyte-like X-CGD PLB-985 cells is sufficient to anchor cytosolic oxidase components and support NADPH oxidase-associated diaphorase activity independent of cytosolic phospholipase A(2) regulation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE FAD; arachidonic acid; cPLA(2) ID CHRONIC GRANULOMATOUS-DISEASE; HUMAN NEUTROPHILS; ESSENTIAL REQUIREMENT; PHENYLARSINE OXIDE; RESPIRATORY BURST; OPSONIZED ZYMOSAN; FLAVOCYTOCHROME-B; CYTOCHROME B(558); NUCLEAR-ENVELOPE; ARACHIDONIC-ACID AB We have previously established a model of cytosolic phospholipase A(2) (cPLA(2))-deficient PLB-985 cells and demonstrated that cPLA(2)-generated arachidonic acid (AA) is essential for reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and NADPH-dependent diaphorase activity. The present study focuses on the C-terminal cytoplasmic domain of gp91(phox) (residues 283-570), which contains the NADPH binding and flavin adenine dinucleotide-reducing center, to determine if this portion is regulated by AA. The gp91(phox) C-terminal reductase domain was expressed in X-CGD PLB-985 cells lacking normal gp91(phox) (X-CGD PLB 91CT cells) and was detected in the plasma membrane. It appears to be bound electrostatically to the plasma membrane, as it is eluted by high salt. Permeabilized, granulocyte-like X-CGD PLB 91CT cells lacking cPLA(2) protein and activity, as well as AA release after stimulation, supported NADPH-dependent diaphorase activity after stimulation, similar to granulocyte-like X-CGD PLB 91CT cells. Normal translocation of p47(phox) and p67(phox) to the membrane fractions of both stimulated cell types indicated that the gpq1(phox) C-terminal region is sufficient to anchor the cytosolic oxidase components to the membranes. cPLA(2) translocated to membranes and bound the assembled oxidase in granulocyte-like X-CGD PLB 91CT cells after stimulation. Therefore, the assembled membrane-bound oxidase complex encompassing the flavin domain of gp91(phox) provides a docking site for cPLA(2) but is not the site of AA-based regulation of oxidase activity. . C1 Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, Infect Dis Lab, IL-84105 Beer Sheva, Israel. Soroka Med Ctr, IL-84101 Beer Sheva, Israel. NIAID, Host Def Lab, NIH, Rockville, MD USA. Indiana Univ, Sch Med, James Whitcomb Riley Hosp Children, Dept Pediat Hematol Oncol, Indianapolis, IN USA. Indiana Univ, Sch Med, James Whitcomb Riley Hosp Children, Herman B Wells Ctr Pediat Res, Indianapolis, IN USA. RP Levy, R (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Biochem, Infect Dis Lab, IL-84105 Beer Sheva, Israel. EM ral@bgumail.bgu.ac.il NR 56 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 2006 VL 80 IS 3 BP 630 EP 639 DI 10.1189/jlb.1105684 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119MF UT WOS:000243015700021 PM 16844764 ER PT J AU Koay, CG Chang, LC Carew, JD Pierpaoli, C Basser, PJ AF Koay, Cheng Guan Chang, Lin-Ching Carew, John D. Pierpaoli, Carlo Basser, Peter J. TI A unifying theoretical and algorithmic framework for least squares methods of estimation in diffusion tensor imaging SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Newton's method; Levenberg-Marquardt; DTI; diffusion tensor; tensor estimation; Hessian ID NOISE; MRI; FEATURES; TISSUES; FIELD AB A unifying theoretical and algorithmic framework for diffusion tensor estimation is presented. Theoretical connections among the least squares (LS) methods, (linear least squares (LLS), weighted linear least squares (WLLS), nonlinear least squares (NLS) and their constrained counterparts), are established through their respective objective functions, and higher order derivatives of these objective functions, i.e., Hessian matrices. These theoretical connections provide new insights in designing efficient algorithms for NLS and constrained NLS (CNLS) estimation. Here, we propose novel algorithms of full Newton-type for the NLS and CNLS estimations, which are evaluated with Monte Carlo simulations and compared with the commonly used Levenberg-Marquardt method. The proposed methods have a lower percent of relative error in estimating the trace and lower reduced chi(2) value than those of the Levenberg-Marquardt method. These results also demonstrate that the accuracy of an estimate, particularly in a nonlinear estimation problem, is greatly affected by the Hessian matrix. In other words, the accuracy of a nonlinear estimation is algorithm-dependent. Further, this study shows that the noise variance in diffusion weighted signals is orientation dependent when signal-to-noise ratio (SNR) is low (<= 5). A new experimental design is, therefore, proposed to properly account for the directional dependence in diffusion weighted signal variance. Published by Elsevier Inc. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. RP Koay, CG (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM guankoac@mail.nih.gov RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 FU Intramural NIH HHS NR 30 TC 121 Z9 121 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 2006 VL 182 IS 1 BP 115 EP 125 DI 10.1016/j.jmr.2006.06.020 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 085MZ UT WOS:000240609500013 PM 16828568 ER PT J AU Oh, SY Romero, R Shim, SS Park, JS Jun, JK Yoon, BH AF Oh, Soo-Young Romero, Roberto Shim, Soon-Sup Park, Joong Shin Jun, Jong Kwan Yoon, Bo Hyun TI Fetal plasma cortisol and dehydroepiandrosterone sulfate concentrations in pregnancy and term parturition SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE human parturition; term; cordocentesis; cortisol; DHEAS; cortisol/DHEAS ratio ID PRETERM LABOR; HUMAN FETUSES; DISEASE; STRESS; SERUM; BIRTH; PROGESTERONE; ENDOCRINE; DELIVERY; INCREASE AB Objective. To examine if changes in fetal plasma concentrations of cortisol or dehydroepiandrosterone sulfate (DHEAS) levels are associated with human term parturition. Methods. Umbilical cord plasma cortisol and DHEAS concentrations were measured in 374 singleton pregnancies that delivered at term in the following six groups: group 1, cordocentesis for clinical indications before 36 weeks of gestation (n = 93); group 2, cordocentesis for clinical indications after 36 weeks of gestation (n = 9); group 3, cord blood sampling after elective cesarean section (CS) at term without labor (n = 140); group 4, cord blood sampling after CS at term with early labor (cervical dilatation <= 3 cm, n = 18); group 5, cord blood sampling after CS at term with active labor (cervical dilatatio 4 cm or greater, n = 26); group 6, cord blood sampling after vaginal delivery at term (n = 88). Corticosteroids were not administered before blood collection. Results. (1) Fetal plasma cortisol remained unchanged until 36 weeks of gestation and increased thereafter to term; (2) active labor was associated with a significant increase in fetal plasma cortisol; (3) fetal plasma DHEAS increased at term gestation (>36 weeks) but did not increase during active labor; (4) the cortisol/DHEAS ratio (stress index) increased with advancing gestation and with active labor at term. Conclusions. Human parturition at term is associated with an increase in fetal plasma cortisol and in the cortisol/DHEAS ratio, but not in DHEAS. C1 Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. Seoul Natl Univ, Lab Fetal Med Res, Clin Res Inst, Seoul 110744, South Korea. Sungkyunkwan Univ, Dept Obstet & Gynecol, Samsung Med Ctr, Sch Med, Suwon, South Korea. NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM Yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011; Jun, Jong Kwan/D-5776-2012; OI Jun, Jong Kwan/0000-0002-0242-1736; Park, Joong Shin/0000-0002-5246-0477 NR 37 TC 12 Z9 12 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD SEP PY 2006 VL 19 IS 9 BP 529 EP 536 DI 10.1080/14767050600853179 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 089JA UT WOS:000240875400002 PM 16966120 ER PT J AU Yaro, AS Dao, A Adamou, A Crawford, E Traore, SF Toure, AM Gwadz, R Lehmann, T AF Yaro, A. S. Dao, A. Adamou, A. Crawford, E. Traore, S. F. Toure, A. M. Gwadz, R. Lehmann, T. TI Reproductive output of female Anopheles gambiae (Diptera : Culicidae): Comparison of molecular forms SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Anopheles gambiae; body size; egg batch size; egg size; fecundity ID WEST-AFRICA; INCIPIENT SPECIATION; MALARIA VECTOR; BODY-SIZE; POPULATION-STRUCTURE; GEOGRAPHIC-VARIATION; LARVAL DEVELOPMENT; DNA ANALYSIS; ADULT SIZE; GENE FLOW AB Knowledge of ecological differences between the molecular forms of Anopheles gambiae Giles (Diptera: Culicidae) might lead to understanding of their unique contribution to disease transmission, to better vector control, and to identification of the forces that have separated them. We compared female fecundity measured as egg batch size in relation to body size between the molecular forms in Mali and contrasted them with their sibling species, Anopheles arabiensis Patton. To determine whether eggs of different egg batches are of similar "quality," we compared the total protein content of first-stage larvae (Lls), collected < 2 h after hatching in deionized water. Egg batch size significantly varied between An. gambiae and An. arabiensis and between the molecular forms of An. gambiae (mean batch size was 186.3, 182.5, and 162.0 eggs in An. arabiensis and the M and the S molecular form of An. gambiae, respectively). After accommodating female body size, however, the difference in batch size was not significant. In the S molecular form, egg protein content was not correlated with egg batch size (r = -0.08, P > 0.7) nor with female body size (r = -0.18, P > 0.4), suggesting that females with more resources invest in more eggs rather than in higher quality eggs. The mean total protein in eggs of the M form (0.407 mu g per L1) was 6% higher than that of the S form (0.384 mu g per L1), indicating that the M form invests a greater portion of her resources into current (rather than future) reproduction. A greater investment per offspring coupled with larger egg batch size may reflect an adaptation of the M form to low productivity larval sites as independent evidence suggests. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Malaria Res & Training Ctr, Bamako, Mali. RP Yaro, AS (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM tlehmann@niaid.nih.gov FU Intramural NIH HHS NR 46 TC 14 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-2585 EI 1938-2928 J9 J MED ENTOMOL JI J. Med. Entomol. PD SEP PY 2006 VL 43 IS 5 BP 833 EP 839 DI 10.1603/0022-2585(2006)43[833:ROOFAG]2.0.CO;2 PG 7 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 085LI UT WOS:000240605200009 PM 17017216 ER PT J AU Pithukpakorn, M Wei, MH Toure, O Steinbach, PJ Glenn, GM Zbar, B Linehan, WM Toro, JR AF Pithukpakorn, M. Wei, M-H Toure, O. Steinbach, P. J. Glenn, G. M. Zbar, B. Linehan, W. M. Toro, J. R. TI Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID ESCHERICHIA-COLI; MUTATIONS; FH; PARAGANGLIOMA; DEFICIENCY; IMPORT; YEAST; GENE; SITE AB Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the autosomal dominant heritable syndrome with predisposition to development of renal cell carcinoma and smooth muscle tumours of the skin and uterus. Objective: To measure the fumarate hydratase (FH) enzyme activity in lymphoblastoid cell lines and fibroblast cell lines of individuals with HLRCC and other familial renal cancer syndromes. Methods: FH enzyme activity was determined in the whole cell, cytosolic, and mitochondrial fractions in 50 lymphoblastoid and 16 fibroblast cell lines including cell lines from individuals with HLRCC with 16 different mutations. Results: Lymphoblastoid cell lines (n = 20) and fibroblast cell lines (n = 11) from individuals with HLRCC had lower FH enzyme activity than cells from normal controls (p < 0.05). The enzyme activity in lymphoblastoid cell lines from three individuals with mutations in R190 was not significantly different from individuals with other missense mutations. The cytosolic and mitochondrial FH activity of cell lines from individuals with HLRCC was reduced compared with those from control cell lines (p < 0.05). There was no significant difference in enzyme activity between control cell lines (n = 4) and cell lines from affected individuals with other hereditary renal cancer syndromes (n = 22). Conclusions: FH enzyme activity testing provides a useful diagnostic method for confirmation of clinical diagnosis and screening of at- risk family members. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Program Div Canc Epidemiol & Genet, Frederick, MD USA. NCI, Urol Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S,Room 7012, Bethesda, MD 20892 USA. EM toroj@mail.nih.gov RI Pithukpakorn, Manop/K-9825-2013 OI Pithukpakorn, Manop/0000-0003-3611-5718 FU Intramural NIH HHS NR 27 TC 28 Z9 28 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2006 VL 43 IS 9 BP 755 EP 762 DI 10.1136/jmg.2006.041087 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 080HV UT WOS:000240239400009 PM 16597677 ER PT J AU Stewart, CL AF Stewart, Colin L. TI One gene- many diseases. The Lamins and the functional architecture of the nucleus SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT British Human Genetics Conference CY SEP 18-20, 2006 CL Univ York, York, ENGLAND HO Univ York C1 NCI, Frederick Canc Res & Dev Ctr, Mammalian Develop Sect, Frederick, MD 21702 USA. EM stewartc@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2006 VL 43 SU 1 BP S22 EP S22 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 090NK UT WOS:000240957800022 ER PT J AU Wong, LJC Yim, D Bai, RK Kwon, H Vacek, MM Zane, J Hoppel, CL Kerr, DS AF Wong, L-J C. Yim, D. Bai, R-K Kwon, H. Vacek, M. M. Zane, J. Hoppel, C. L. Kerr, D. S. TI A novel mutation in the mitochondrial tRNA (Ser(AGY)) gene associated with mitochondrial myopathy, encephalopathy, and complex I deficiency SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; QUANTITATIVE PCR ANALYSIS; LACTIC-ACIDOSIS; OXIDATIVE-PHOSPHORYLATION; DIAGNOSTIC-CRITERIA; DNA MUTATIONS; DISEASE; DISORDERS; ENCEPHALOMYOPATHY; QUANTIFICATION AB Purpose: To identify molecular defects in a girl with clinical features of MELAS (mitochondrial encephalomyopathy and lactic acidosis) and MERRF (ragged-red fibres) syndromes. Methods: The enzyme complex activities of the mitochondrial respiratory chain were assayed. Temporal temperature gradient gel electrophoresis was used to scan the entire mitochondrial genome for unknown mitochondrial DNA (mtDNA) alterations, which were then identified by direct DNA sequencing. Results: A novel heteroplasmic mtDNA mutation, G12207A, in the tRNA(Ser(AGY)) gene was identified in the patient who had a history of developmental delay, feeding difficulty, lesions within her basal ganglia, cerebral atrophy, proximal muscle weakness, increased blood lactate, liver dysfunction, and fatty infiltration of her muscle. Muscle biopsy revealed ragged red fibres and pleomorphic mitochondria. Study of skeletal muscle mitochondria revealed complex I deficiency associated with mitochondrial proliferation. Real time quantitative PCR analysis showed elevated mtDNA content, 2.5 times higher than normal. The tRNASer(AGY) mutation was found in heteroplasmic state (92%) in the patient's skeletal muscle. It was not present in her unaffected mother's blood or in 200 healthy controls. This mutation occurs at the first nucleotide of the 59 end of tRNA, which is involved in the formation of the stem region of the amino acid acceptor arm. Mutation at this position may affect processing of the precursor RNA, the stability and amino acid charging efficiency of the tRNA, and overall efficiency of protein translation. Conclusion: This case underscores the importance of comprehensive mutational analysis of the entire mitochondrial genome when a mtDNA defect is strongly suggested. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. Kaiser Permanente Med Grp, Honolulu, HI USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Ctr Inherited Disorders Energy Metab, Cleveland, OH 44106 USA. RP Wong, LJC (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza,NAB 2015, Houston, TX 77030 USA. EM ljwong@bcm.edu NR 35 TC 16 Z9 17 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2006 VL 43 IS 9 AR e46 DI 10.1136/jmg.2005.040626 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 080HV UT WOS:000240239400011 PM 16950817 ER PT J AU Pietruchinski, E Benati, F Lauretti, F Kisielius, J Ueda, M Volotao, EM Soares, CC Hoshino, Y Linhares, REC Nozawa, C Santos, N AF Pietruchinski, Eduardo Benati, Fabricio Lauretti, Flavio Kisielius, Jonas Ueda, Marli Volotao, Eduardo M. Soares, Caroline C. Hoshino, Yasutaka Linhares, Rosa Elisa C. Nozawa, Carlos Santos, Norma TI Rotavirus diarrhea in children and adults in a southern city of Brazil in 2003: Distribution of G/P types and finding of a rare G12 strain SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE rotavirus; G12; genotyping; gastroenteritis ID GROUP-A ROTAVIRUS; POLYMERASE CHAIN-REACTION; RIO-DE-JANEIRO; SAO-PAULO; ACUTE GASTROENTERITIS; ANTIGENIC VARIATION; MIXED INFECTIONS; NUCLEIC-ACID; IDENTIFICATION; GENOTYPE AB Between May and August in 2003, a total of 251 fecal samples were collected from children and adults with diarrhea (5 inpatients and 246 outpatients) at a private hospital in the city of Ponta Grossa, the state of Parana, Brazil. Group A rotavirus was detected in 71 of 251 (28.3%) specimens: 55 (77.5%) from children under 5 years of age and 16 (22.5%) from individuals aged 6-72 years. All 71 strains exhibited a "long" RNA pattern when analyzed by PAGE. Sixty-one positive samples that yielded enough RNA were submitted to PCR genotyping. The most frequent G/P genotype combination detected was G1P[8] (86.9%; 53/61) followed by G9P[8](3.3%; 2/61) and G12P[9](1.6%; 1/61). Rotaviruses with G2, G3, G4, P[4], or P[6] specificity were not detected. For three strains (4.9%) bearing G1 genotype, the VP4 specificity could no be determined, and two specimens (3.3%) remained G/P non-typeable. One rotavirus strain (HC91) bearing G12P[9] genotype with a "long" electropherotype was isolated from an 11-month-old boy with diarrhea for the first time in Brazil. The cell-culture grown HC91 strain was shown to belong to serotype G12 by neutralization. C1 Fed Univ Rio De Janeiro, Dept Virol, Inst Microbiol, BR-21941590 Rio De Janeiro, Brazil. Univ Estadual Londrina, Dept Microbiol, Ctr Ciencias Biol, Londrina, PR USA. Inst Adolfo Lutz Registro, Secao Microscopia Elect, Sao Paulo, Brazil. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Fed Univ Rio De Janeiro, Dept Virol, Inst Microbiol, Cidade Univ,CCS Bl 1, BR-21941590 Rio De Janeiro, Brazil. EM nsantos@micro.ufrj.br RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU Intramural NIH HHS NR 67 TC 46 Z9 46 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 2006 VL 78 IS 9 BP 1241 EP 1249 DI 10.1002/jmv.20686 PG 9 WC Virology SC Virology GA 068WE UT WOS:000239404400014 PM 16847962 ER PT J AU McDonald, MD Smith, CP Walsh, PJ AF McDonald, M. D. Smith, C. P. Walsh, P. J. TI The physiology and evolution of urea transport in fishes SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE facilitated diffusion; active transport; UT-A; gill; kidney; excretion ID TOADFISH OPSANUS-BETA; MEDULLARY COLLECTING DUCT; TROUT ONCORHYNCHUS-MYKISS; NITROGENOUS WASTE EXCRETION; DOGFISH SQUALUS-ACANTHIAS; WATER RAINBOW-TROUT; LAKE MAGADI TILAPIA; EARLY-LIFE STAGES; EARTHWORM LUMBRICUS TERRESTRIS; EXTREMELY ALKALINE ENVIRONMENT AB This review summarizes what is currently known about urea transporters in fishes in the context of their physiology and evolution within the vertebrates. The existence of urea transporters has been investigated in red blood cells and hepatocytes of fish as well as in renal and branchial cells. Little is known about urea transport in red blood cells and hepatocytes, in fact, urea transporters are not believed to be present in the erythrocytes of elasmobranchs nor in teleost fish. What little physiological evidence there is for urea transport across fish hepatocytes is not supported by molecular evidence and could be explained by other transporters. In contrast, early findings on elasmobranch renal urea transporters were the impetus for research in other organisms. Urea transport in both the elasmobranch kidney and gill functions to retain urea within the animal against a massive concentration gradient with the environment. Information on branchial and renal urea transporters in teleost fish is recent in comparison but in teleosts urea transporters appear to function for excretion and not retention as in elasmobranchs. The presence of urea transporters in fish that produce a copious amount of urea, such as elasmobranchs and ureotelic teleosts, is reasonable. However, the existence of urea transporters in ammoniotelic fish is curious and could likely be due to their ability to manufacture urea early in life as a means to avoid ammonia toxicity. It is believed that the facilitated diffusion urea transporter (UT) gene family has undergone major evolutionary changes, likely in association with the role of urea transport in the evolution of terrestriality in the vertebrates. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Manchester, Fac Life Sci, Manchester M13 9PT, Lancs, England. Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada. RP McDonald, MD (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM dmcdonald@rsmas.miami.edu NR 127 TC 41 Z9 43 U1 4 U2 38 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 2006 VL 212 IS 2 BP 93 EP 107 DI 10.1007/s00232-006-0869-5 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 136BZ UT WOS:000244198900004 PM 17264987 ER PT J AU Fenton, RA Smith, CP Knepper, MA AF Fenton, R. A. Smith, C. P. Knepper, M. A. TI Role of collecting duct urea transporters in the kidney - Insights from mouse models SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE UT-A; urinary concentrating mechanism; countercurrent multiplication ID URINE CONCENTRATING ABILITY; RAT-KIDNEY; UT-A; MAMMALIAN KIDNEY; VASA-RECTA; GLOMERULAR-FILTRATION; WATER TRANSPORT; KNOCKOUT MICE; INNER MEDULLA; COUNTERCURRENT MULTIPLICATION AB Urea movement across plasma membranes is modulated by specialized urea transporter proteins. These proteins are proposed to play key roles in the urinary concentrating mechanism and fluid homeostasis. To date, two urea-transporter genes have been cloned; UT-A (Slc14a2), encoding at least five proteins and UT-B (Slc14a1) encoding a single protein isoform. Recently we engineered mice that lack the inner medullary collecting duct (IMCD) urea transporters, UT-A1 and UT-A3 (UT-A1/3(-/-) mice). This article includes 1) a historical review of the role of renal urea transporters in renal function; 2) a review of our studies utilizing the UT-A1/3(-/-) mice; 3) description of an additional line of transgenic mice in which beta-galactosidase expression is driven by the alpha-promoter of the UT-A gene, which is allowing better physiological definition of control mechanisms for UT-A expression; and 4) a discussion of the implications of the studies in transgenic mice for the teaching of kidney physiology. C1 Univ Aarhus, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Fenton, RA (reprint author), Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Bldg 123, DK-8000 Aarhus, Denmark. EM ROFE@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 91 TC 10 Z9 10 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 2006 VL 212 IS 2 BP 119 EP 131 DI 10.1007/s00232-006-0871-y PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 136BZ UT WOS:000244198900006 PM 17264985 ER PT J AU Maeng, JS Bae, KS Kwak, J AF Maeng, Jin-Soo Bae, Kyung-Sook Kwak, Jangyul TI Gene disruption using in vivo and in vitro methylation in Streptomyces griseus SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE transformation; methylation; gene disruption; Streptomyces griseus; homologous recombination ID A-FACTOR; RESTRICTION SYSTEM; BIOSYNTHETIC GENES; ESCHERICHIA-COLI; BALD MUTANTS; SPORULATION; IDENTIFICATION; TRANSFORMATION; REPLACEMENT; COELICOLOR AB Previous study demonstrated that the restriction barrier of Streptomyces griseus is almost completely bypassed by the Streptomyces-E coli shuttle vectors passed through the E coli GM161 strain and methylated with AluI and HpaII methyltransferases. ne same DNA methylation of the genomic DNA fragments cloned the nonreplicative vectors generated integrative transformation and gene disruption of their chromosomal counterparts at high efficiencies in S. griseus. This result indicated that the efficiency of gene disruption depends on the efficient transfer of the incoming DNA into bacterial hosts. C1 Korea Res Inst Biosci & Biotechnol, Lab Insect Resources, Taejon 305333, South Korea. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kwak, J (reprint author), Korea Res Inst Biosci & Biotechnol, Lab Insect Resources, Taejon 305333, South Korea. EM jkwak@kribb.re.kr NR 31 TC 0 Z9 0 U1 1 U2 1 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 EI 1738-8872 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD SEP PY 2006 VL 16 IS 9 BP 1472 EP 1476 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 089PG UT WOS:000240892200023 ER PT J AU Tong, W Kulaeva, OI Clark, DJ Lutter, LC AF Tong, Wilbur Kulaeva, Olga I. Clark, David J. Lutter, Leonard C. TI Topological analysis of plasmid chromatin from yeast and mammalian cells SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE chromatin; DNA topology; nucleosome; nucleosome repeat length; supercoiling ID NUCLEOSOME CORE PARTICLE; TRANSCRIPTION ELONGATION COMPLEX; CEREVISIAE LINKER HISTONE; LINKING NUMBER CHANGE; SIMIAN VIRUS 40; SACCHAROMYCES-CEREVISIAE; TRANSCRIBING CHROMATIN; NUCLEASE DIGESTION; SUPERHELICAL TURNS; DNA AB Yeast has proven to be a powerful system for investigation of chromatin structure. However, the extent to which yeast chromatin can serve as a model for mammalian chromatin is limited by the significant number of differences that have been reported. To further investigate the structural relationship between the two chromatins, we have performed a DNA topological analysis of pRSSVO, a 5889 base-pair plasmid that can replicate in either yeast or mammalian cells. When grown in mammalian cells, pRSSVO contains an average of 33 negative supercoils, consistent with one nucleosome per 181 bp. This is close to the measured nucleosome repeat length of 190 bp. However, when grown in yeast cells, pRSSVO contains an average of only 23 negative supercoils, which is indicative of only one nucleosome per 256 bp. This is dramatically different from the measured nucleosome repeat length of 165 bp. To account for these observations, we suggest that yeast chromatin is composed of relatively short ordered arrays of nucleosomes with a repeat of 165 bp, separated by substantial gaps, possibly corresponding to regulatory regions. (c) 2006 Elsevier Ltd. All rights reserved. C1 Henry Ford Hosp, Mol Biol Res Program, Detroit, MI 48202 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Lutter, LC (reprint author), Henry Ford Hosp, Mol Biol Res Program, Floor 5D,1 Ford Pl, Detroit, MI 48202 USA. EM llutter1@hfhs.org RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 FU Intramural NIH HHS; NIGMS NIH HHS [GM-49988, GM-56216] NR 46 TC 10 Z9 10 U1 1 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 1 PY 2006 VL 361 IS 5 BP 813 EP 822 DI 10.1016/j.jmb.2006.07.015 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082CZ UT WOS:000240365600001 PM 16890953 ER PT J AU Burroughs, AM Allen, KN Dunaway-Mariano, D Aravind, L AF Burroughs, A. Maxwell Allen, Karen N. Dunaway-Mariano, Debra Aravind, L. TI Evolutionary genomics of the HAD superfamily: Understanding the structural adaptations and catalytic diversity in a superfamily of phosphoesterases and allied enzymes SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Review DE Rossmann fold; catalytic diversity; lateral gene transfer; substrate specificity; domain mobility ID RNA-POLYMERASE-II; P-TYPE ATPASE; MULTIPLE SEQUENCE ALIGNMENT; TERMINAL-DOMAIN-PHOSPHATASE; PHOSPHONOACETALDEHYDE HYDROLASE CATALYSIS; HALOACID DEHALOGENASE SUPERFAMILY; METHIONINE SALVAGE PATHWAY; SITE-DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI AB The HAD (haloacid dehalogenase) superfamily includes phosphoesterases, ATPases, phosphonatases, dehalogenases, and sugar phosphomutases acting on a remarkably diverse set of substrates. The availability of numerous crystal structures of representatives belonging to diverse branches of the HAD superfamily provides us with a unique opportunity to reconstruct their evolutionary history and uncover the principal determinants that led to their diversification of structure and function. To this end we present a comprehensive analysis of the HAD superfamily that identifies their unique structural features and provides a detailed classification of the entire superfamily. We show that at the highest level the HAD superfamily is unified with several other superfamilies, namely the DHH, receiver (CheY-like), von Willebrand A, TOPRIM, classical histone deacetylases and PIN/FLAP nuclease domains, all of which contain a specific form of the Rossmannoid fold. These Rossmannoid folds are distinguished from others by the presence of equivalently placed acidic catalytic residues, including one at the end of the first core beta-strand of the central sheet. The HAD domain is distinguished from these related Rossmannoid folds by two key structural signatures, a "squiggle" (a single helical turn) and a "flap" (a beta hairpin motif) located immediately downstream of the first beta-strand of their core Rossmanoid fold. The squiggle and the flap motifs are predicted to provide the necessary mobility to these enzymes for them to alternate between the "open" and "closed" conformations. In addition, most members of the HAD superfamily contains inserts, termed caps, occurring at either of two positions in the core Rossmannoid fold. We show that the cap modules have been independently inserted into these two stereotypic positions on multiple occasions in evolution and display extensive evolutionary diversification independent of the core catalytic domain. The first group of caps, the C1 caps, is directly inserted into the flap motif and regulates access of reactants to the active site. The second group, the C2 caps, forms a roof over the active site, and access to their internal cavities might be in part regulated by the movement of the flap. The diversification of the cap module was a major factor in the exploration of a vast substrate space in the course of the evolution of this superfamily. We show that the HAD superfamily contains 33 major families distributed across the three superkingdoms of life. Analysis of the phyletic patterns suggests that at least five distinct HAD proteins are traceable to the last universal common ancestor (LUCA) of all extant organisms. While these prototypes diverged prior to the emergence of the LUCA, the major diversification in terms of both substrate specificity and reaction types occurred after the radiation of the three superkingdoms of life, primarily in bacteria. Most major diversification events appear to correlate with the acquisition of new metabolic capabilities, especially related to the elaboration of carbohydrate metabolism in the bacteria. The newly identified relationships and functional predictions provided here are likely to aid the future exploration of the numerous poorly understood members of this large superfamily of enzymes. Published by Elsevier Ltd. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. Univ New Mexico, Dept Chem, Albuquerque, NM 87131 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov OI Allen, Karen/0000-0001-7296-0551 FU Intramural NIH HHS; NIGMS NIH HHS [GM61099] NR 196 TC 195 Z9 198 U1 2 U2 25 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 1 PY 2006 VL 361 IS 5 BP 1003 EP 1034 DI 10.1016/j.jmb.2006.06.049 PG 32 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 082CZ UT WOS:000240365600016 PM 16889794 ER PT J AU Costanzi, S Vincenzetti, S Cristalli, G Vita, A AF Costanzi, Stefano Vincenzetti, Silvia Cristalli, Gloria Vita, Alberto TI Human cytidine deaminase: A three-dimensional homology model of a tetrameric metallo-enzyme inferred from the crystal structure of a distantly related dimeric homologue SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE cytidine deaminase; homology modeling; sequence alignment; phylogenetic analysis; evolution ID MULTIPLE SEQUENCE ALIGNMENT; PURIFICATION; STRATEGIES; EXPRESSION; CLONING AB Cytidine deaminase (CDA) is a cytosolic metalloprotein whose functional unit can be either a homotetramer (T-CDA) or a homodimer (DCDA), depending on the species. In 1994, the first crystal structure of the dimeric Escherichia coli CDA has been published. However, a crystal structure of a tetrameric CDA was not determined until 2002. Prior to the disclosure of the experimentally elucidated structure of a tetrameric CDA, we derived a homology model of the-human T-CDA employing the crystal structure of the dimeric E. coli CDA as a template. The comparison of our theoretical model with the crystal structure of the human T-CDA, subsequently published in 2004, validates our prediction: not only of the structural features of the monomer and the details of the binding site, but also the multimeric arrangement of the subunits were determined with high accuracy in our model. By means of a phylogenetic analysis conducted on CDAs from various organisms, we demonstrate that the E. coli CDA is one of the furthest known homologues of the human enzyme. Nonetheless, despite the evolutionary distance and, more importantly, the different multimeric arrangement of their functional units, the E. coli CDA proved to have all the necessary information to accurately infer the structure of its human homologue. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDDKD, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. Univ Camerino, Dipartimento Sci Vet, I-62032 Camerino, Italy. Univ Camerino, Dipartimento Sci Chim, I-62032 Camerino, Italy. RP Costanzi, S (reprint author), NIDDKD, Computat Chem Core Lab, NIH, 12A Ctr Dr Rm 4051 MSC 5646, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov RI Costanzi, Stefano/G-8990-2013; OI Costanzi, Stefano/0000-0003-3183-7332 NR 22 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD SEP PY 2006 VL 25 IS 1 BP 10 EP 16 DI 10.1016/j.jmgm.2005.10.008 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA 094YO UT WOS:000241275500002 PM 16303324 ER PT J AU Floriano, WB Hall, S Vaidehi, N Kim, U Drayna, D Goddard, WA AF Floriano, Wely B. Hall, Spencer Vaidehi, Nagarajan Kim, Unkyung Drayna, Dennis Goddard, William A., III TI Modeling the human PTC bitter-taste receptor interactions with bitter tastants SO JOURNAL OF MOLECULAR MODELING LA English DT Article DE phenylthiocarbamide; bitter; protein structure; G protein-coupled receptor; taste perception ID PROTEIN-COUPLED RECEPTORS; CONFORMATIONAL-CHANGES; RANDOM MUTAGENESIS; ACTIVATION; RHODOPSIN; SENSITIVITY; PERCEPTION; PHENYLTHIOCARBAMIDE; INDIVIDUALS; PREDICTION AB We employed the first principles computational method MembStruk and homology modeling techniques to predict the 3D structures of the human phenylthiocarbamide (PTC) taste receptor. This protein is a seven-transmembrane-domain G protein-coupled receptor that exists in two main forms worldwide, designated taster and nontaster, which differ from each other at three amino-acid positions. 3D models were generated with and without structural similarity comparison to bovine rhodopsin. We used computational tools (HierDock and ScanBindSite) to generate models of the receptor bound to PTC ligand to estimate binding sites and binding energies. In these models, PTC binds at a site distant from the variant amino acids, and PTC binding energy was equivalent for both the taster and nontaster forms of the protein. These models suggest that the inability of humans to taste PTC is due to a failure of G protein activation rather than decreased binding affinity of the receptor for PTC. Amino-acid substitutions in the sixth and seventh transmembrane domains of the nontaster form of the protein may produce increased steric hindrance between these two alpha-helices and reduce the motion of the sixth helix required for G protein activation. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. CALTECH, Mat & Proc Simulat Ctr, Pasadena, CA 91125 USA. Kyungpook Natl Univ, Dept Biol, Taegu 702701, South Korea. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU NIAID NIH HHS [R29AI40567]; NICHD NIH HHS [HD36385]; NIGMS NIH HHS [R01-GM625523]; PHS HHS [Z01-000046-04] NR 44 TC 40 Z9 43 U1 3 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1610-2940 J9 J MOL MODEL JI J. Mol. Model. PD SEP PY 2006 VL 12 IS 6 BP 931 EP 941 DI 10.1007/s00894-006-0102-6 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science GA 089SJ UT WOS:000240900700022 PM 16607493 ER PT J AU Goldstein, RB Grant, BF Ruan, WJ Smith, SM Saha, TD AF Goldstein, Rise B. Grant, Bridget F. Ruan, W. June Smith, Sharon M. Saha, Tulshi D. TI Antisocial personality disorder with childhood- vs adolescence-onset conduct disorder - Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE antisocial personality disorder; conduct disorder; age at onset; comorbidity ID AGE-OF-ONSET; SUBSTANCE-USE DISORDERS; LIFE-COURSE-PERSISTENT; DRUG-USE DISORDERS; AXIS-II DISORDERS; ANXIETY DISORDERS; UNITED-STATES; PSYCHIATRIC COMORBIDITY; MAJOR DEPRESSION; BIPOLAR DISORDER AB This study, based on a nationally representative, epidemiologic sample (N = 43,093, response rate 81%), compared sociodemographic and family history correlates, antisocial personality disorder (ASPD) symptom patterns, and Axis I and Axis 11 comorbidity, among adults with DSM-IV ASPD who reported onset of conduct disorder (CD) in childhood (< age 10) versus adolescence (>= age 10). Prevalence of each ASPD diagnostic criterion and comorbid lifetime disorder was estimated. Logistic regression was used to examine associations of childhood-onset CD with ASPD symptom patterns and comorbid disorders. Among the 1422 respondents with ASPD, 447 reported childhood-onset CD. Childhood-onset respondents were more likely than adolescence-onset respondents to endorse CD criteria involving aggression against persons, animals, and property before age 15, and to endorse more childhood criteria and lifetime violent behaviors. Childhood-onset respondents displayed significantly elevated odds of lifetime social phobia, generalized anxiety disorder, drug dependence, and paranoid, schizoid, and avoidant personality disorders, but significantly decreased odds for lifetime tobacco dependence. Childhood-onset CD appears to identify a more polysymptomatic and violent form of ASPD, associated with greater lifetime comorbidity for selected Axis I and Axis 11 disorders, in nonclinical populations. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3068, Bethesda, MD 20892 USA. OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS NR 63 TC 40 Z9 40 U1 15 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 2006 VL 194 IS 9 BP 667 EP 675 DI 10.1097/01.nmd.0000235762.82264.a1 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 084HY UT WOS:000240525200006 PM 16971818 ER PT J AU Chiba, S Hashimoto, R Hattori, S Yohda, M Lipska, B Weinberger, DR Kunugi, H AF Chiba, S. Hashimoto, R. Hattori, S. Yohda, M. Lipska, B. Weinberger, D. R. Kunugi, H. TI Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE antipsychotic; DISC1; dysbindin; schizophrenia; gene expression ID GENE DTNBP1; PREFRONTAL CORTEX; NEURITE OUTGROWTH; RAT HIPPOCAMPUS; RISK HAPLOTYPE; 6P22.3 GENE; SCHIZOPHRENIA; ASSOCIATION; DISRUPTED-IN-SCHIZOPHRENIA-1; PROTEIN AB Altered expression of Disrupted-In-Schizophrenia-1 (DISC1) and dysbindin (DTNBP1), susceptibility genes for schizophrenia, in schizophrenic brain has been reported; however, the possible effect of antipsychotics on the expression levels of these genes has not yet been studied. We measured the mRNA expression levels of these genes in frontal cortex and hippocampus of mice chronically treated with typical and atypical antipsychotics by a real-time quantitative RT-PCR method. We found that atypical antipsychotics, olanzapine and risperidone, in a clinically relevant dose increased DISC1 expression levels in frontal cortex, while a typical antipsychotic, haloperidol, did not. No significant effect on dysbindin expression levels was observed in either brain region. These data suggest that prior evidence of decreased expression of dysbindin in postmortem brain of schizophrenics is not likely to be a simple artifact of antemortem drug treatment. Our results also suggest a potential role of DISC1 in the therapeutic mechanisms of certain atypical antipsychotics. C1 Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorders Res, Kodaira, Tokyo 1878502, Japan. Tokyo Univ Agr & Technol, Dept Biotechnol & Life Sci, Koganei, Tokyo, Japan. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chiba, S (reprint author), Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorders Res, 4-1-1 Ogawahigashi, Kodaira, Tokyo 1878502, Japan. EM rhashimo@ncnp.go.jp RI Yohda, Masafumi/A-5149-2013; Hashimoto, Ryota/P-8572-2014; OI Yohda, Masafumi/0000-0001-8307-9671; Hashimoto, Ryota/0000-0002-5941-4238; Kunugi, Hiroshi/0000-0002-7209-3790 NR 34 TC 36 Z9 38 U1 0 U2 3 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD SEP PY 2006 VL 113 IS 9 BP 1337 EP 1346 DI 10.1007/s00702-005-0414-1 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 078IZ UT WOS:000240097500021 PM 16463116 ER PT J AU Kapadia, R Tureyen, K Bowen, KK Kalluri, H Johnson, PF Vemuganti, R AF Kapadia, Ramya Tureyen, Kudret Bowen, Kellie K. Kalluri, Haviryaji Johnson, Peter F. Vemuganti, Raghu TI Decreased brain damage and curtailed inflammation in transcription factor CCAAT/enhancer binding protein beta knockout mice following transient focal cerebral ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE gene expression; infarction; interleukin-6; microarray; silencer factor-B; stroke ID INTERCELLULAR-ADHESION MOLECULE-1; INDUCIBLE FACTOR-I; FACTOR-KAPPA-B; GENE-EXPRESSION; C/EBP-BETA; MICROARRAY ANALYSIS; NUCLEAR-FACTOR; RAT-BRAIN; ARTERY OCCLUSION; TARGET GENES AB CCAAT/enhancer binding protein beta (C/EBP beta) is a leucine-zipper transcription factor that regulates cell growth and differentiation in mammals. Expression of many pro-inflammatory genes including the cytokine interleukin-6 is known to be controlled by C/EBP beta. We report that focal cerebral ischemia induced by transient middle cerebral artery occlusion (MCAO) significantly increases C/EBP beta gene expression in mouse brain at between 6 and 72 h of reperfusion. To understand the functional significance of C/EBP beta in postischemic inflammation and brain damage, we induced transient MCAO in cohorts of adult C/EBP beta null mice and their wild-type littermates. At 3 days of reperfusion following transient MCAO, C/EBP beta null mice showed significantly smaller infarcts, reduced neurological deficits, decreased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, decreased intercellular adhesion molecule 1 (ICAM1) immunopositive vessels, decreased extravasated neutrophils and fewer activated microglia/macrophages, compared with their wild-type littermates. Furthermore, GeneChip analysis showed that postischemic induction of many transcripts known to promote inflammation and neuronal damage was less pronounced in the brains of C/EBP beta-/- mice compared with C/EBP beta+/+ mice. These results suggest a significant role for C/EBP beta in postischemic inflammation and brain damage. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. Univ Wisconsin, Neurosci Training Program, Madison, WI 53792 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI 53792 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Vemuganti, R (reprint author), Univ Wisconsin, Dept Neurol Surg, K4-8 Mail Stop Code CSC-8660,600 Highland Ave, Madison, WI 53792 USA. EM vemugant@neurosurg.wisc.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NIGMS NIH HHS [T32 GM07507]; NINDS NIH HHS [R01 NS044173, R01 NS049448] NR 57 TC 55 Z9 57 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2006 VL 98 IS 6 BP 1718 EP 1731 DI 10.1111/j.1471-4159.2006.04056.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 077MN UT WOS:000240033600003 PM 16899075 ER PT J AU Rapaka, R Khalsa, J Gendelman, H AF Rapaka, Rao Khalsa, Jag Gendelman, Howard TI Welcome SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Editorial Material C1 [Rapaka, Rao; Khalsa, Jag] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Gendelman, Howard] Univ Nebraska Med Ctr, Omaha, NE 68182 USA. RP Rapaka, R (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5213, Bethesda, MD 20892 USA. EM rrapaka@nida.nih.gov NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2006 VL 1 IS 3 BP 193 EP 194 DI 10.1007/s11481-006-9033-3 PG 2 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA V04MW UT WOS:000207063500001 ER PT J AU Wakita, H Hallenbeck, JM AF Wakita, Hideaki Hallenbeck, John M. TI Protective effect of mucosal tolerance to E-selectin against memory impairment and white matter injury in a rat model of vascular dementia SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Natl Ctr Geriat & Gerontol, Natl Inst Longev Sci, Dept Vasc Dementia Res, Obu, Japan. NIMH, NINCDS, Stroke Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 20 EP 20 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100035 ER PT J AU Cunningham, MW Cox, CJ Swedo, SE Kirvan, CA AF Cunningham, M. W. Cox, C. J. Swedo, S. E. Kirvan, C. A. TI Molecular mimicry, autoimmunity, and infection SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 34 EP 35 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100089 ER PT J AU Carr, DJJ Wuest, T Welner, R Pelayo, R Farber, J Luster, A Kincade, P AF Carr, D. J. J. Wuest, T. Welner, R. Pelayo, R. Farber, J. Luster, A. Kincade, P. TI CXCL10 but not CXCL9 deficient mice are highly sensitive to herpes simplex virus type 1 infection SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. NIH, NIAID, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 42 EP 42 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100106 ER PT J AU Bielekova, B Catalfamo, M Reichert-Scrivner, S Packer, A Cerna, M Waldmann, TA McFarland, H Henkart, P Martin, R AF Bielekova, B. Catalfamo, M. Reichert-Scrivner, S. Packer, A. Cerna, M. Waldmann, T. A. McFarland, H. Henkart, P. Martin, R. TI Successful therapy of multiple sclerosis (MS) targeting high-affinity IL-2 receptor reveals regulatory role of CD56(bright) NK cells on T cell responses in humans SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 NIH, NINDS, Neuroimmunol Branch, Bethesda, MD USA. Univ Cincinnati, Waddell Ctr MS, Dept Neurol, Cincinnati, OH USA. NIH, NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIH, NCI, Metabolism Branch, Bethesda, MD 20892 USA. Hosp Universitari Vall D Hebron, Catalan Inst Res & Advanced Studies, Unit Neuroimmunol, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 54 EP 54 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100131 ER PT J AU Bangham, CRM Jacobson, S AF Bangham, Charles R. M. Jacobson, Steven TI Immune containment and cell to cell spread of the human leukemia virus HTLV-1 SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Univ London Imperial Coll Sci & Technol, Wright Fleming Inst, Dept Immunol, London, England. Natl Inst Hlth, Bethesda, MD USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 72 EP 72 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100166 ER PT J AU Schmidt, J Raju, R Salajegheh, M Rakocevic, G Dalakas, MC AF Schmidt, J. Raju, R. Salajegheh, M. Rakocevic, G. Dalakas, M. C. TI Molecular interactions between inflammation and beta-amyloid-associated degeneration in sporadic Inclusion Body Myositis (sIBM) muscle SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 NIH, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Univ Gottingen, Dept Neuroimmunol & Neurol, D-3400 Gottingen, Germany. RI Raju, Raghavan/E-9219-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 96 EP 96 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100211 ER PT J AU Ahlqvist, J Hammarstedt, M Jacobson, S Garoff, H Fogdell-Hahn, A AF Ahlqvist, J. Hammarstedt, M. Jacobson, S. Garoff, H. Fogdell-Hahn, A. TI Identification of host cell proteins in purified infectious humanherpesvirus 6A (HHV-6A) viral particles SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Karolinska Inst, Huddinge, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 114 EP 114 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100238 ER PT J AU Harry, GJ d'Hellencourt, CL Wine, R Aoyama, M AF Harry, G. J. d'Hellencourt, C. Lefebvre Wine, R. Aoyama, M. TI Differential vulnerability of hippocampal neurons: Relationship of tumor necrosis factor and glia in chemical-induced injury SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Natl Inst Environm Hlth Sci, NIH, DHHS, Neurobiol Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 129 EP 129 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633100262 ER PT J AU Zhang, N Oppenheim, J AF Zhang, Ning Oppenheim, Joost TI Crosstalk between chemokine, opioid, and vanilloid receptors SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Natl Canc Inst, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Peking Univ, Coll Chem, State Key Lab Mol Dynam & Stable Struct, Beijing 100871, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 171 EP 171 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633101117 ER PT J AU Aoyama, M Grissom, SF Gohlke, J Harry, GJ AF Aoyama, Mineyoshi Grissom, Sherry F. Gohlke, Julia Harry, G. Jean TI Age and injury-related molecular profiling of the subgranular zone (SGZ) in CD1 mice: Contribution to hippocampal injury-induced neurogenesis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 8th International Conference of Neuroimmunology CY OCT 15-19, 2006 CL Nagoya, JAPAN C1 Natl Inst Hlth, DHHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. Natl Inst Hlth, DHHS, Res Triangle Pk, NC 27709 USA. Natl Inst Hlth, Natl Inst Environm Hlth Sci, Microarray Grp, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2006 VL 178 SU 1 BP 268 EP 268 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 099YG UT WOS:000241633101401 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. TI Role of IVIg in autoimmune, neuroinflammatory and neurodegenerative disorders of the central nervous system: present and future prospects SO JOURNAL OF NEUROLOGY LA English DT Article DE autoimmune disorders; IVIg; neuroinflammation; neurodegeneration ID GLUTAMIC-ACID DECARBOXYLASE; STIFF-MAN-SYNDROME; INTRAVENOUS IMMUNOGLOBULIN THERAPY; PERSON SYNDROME; INFLAMMATORY MYOPATHIES; ALZHEIMERS-DISEASE; POSTPOLIO SYNDROME; NEUROMUSCULAR DISEASES; LEUKOCYTE RECRUITMENT; CONTROLLED-TRIAL AB Introduction Although IVIg is highly effective in several autoimmune neuromuscular disorders (neuropathies, myopathies and neuromuscular junction disorders), its effectiveness in autoimmune or neuroinflammatory CNS diseases, with the exception of multiple sclerosis, has not been explored. Emerging data suggest that IVIg may have a role not only in certain antibody-mediated CNS diseases but also in some neurodegenerative disorders associated with "neuroinflammation" mediated by proinflammatory cytokines. Methods Data from a previously reported controlled study conducted in patients with stiff person syndrome (SPS) are presented as a paradigm of a CNS disorder associated with specific autoantibodies responding to IVIg. Emerging data using IVIg in various neuroinflammatory and neurodegenerative conditions such as Alzheimers disease, postpolio syndrome (PPS), fibrotic disorders, chronic painful conditions and narcoplepsy are summarized. Results On the basis of a double-blind placebo-controlled trial conducted in SPS patients with high anti-GAD antibodies, IVIg was shown to be effective resulting in improvement of stiffness and heightened sensitivity scores and increasing the patients' ability to carry out daily activities. In SPS, IVIg also suppressed the anti-GAD antibodies titers probably via an anti-idiotypic effect. A controlled study in patients with PPS, showed reduction in cytokines in serum and CSF with concomitant improvement in the patients' strength and ability to carry out their daily activities. The effect of IVIg in a small number of patients with Alzheimer's disease was promising by reducing the ADAS-cog scores, suggesting a reversal of disease progression. IVIg has been shown to have an effect on tissue fibrosis and in certain subacute painful conditions by suppressing cytokines that mediate fibrosis or pain. In another uncontrolled study, IVIg reduced the number of cataplectic attacks in narcolepsy patients. Conclusions IVIg is effective in anti-GAD-positive patients with SPS. Whether it is also effective in other GAD-positive CNS disorders such as epilepsies, cerebellar degenerations or Batten's disease need to be studied in control trials. Emerging data suggest that IVIg, by suppressing proinflammatory cytokines, may exert a beneficial effect in patients with Alzheimer's disease, postpolio syndrome, chronic pain syndromes, fibrotic disorders and narcolepsy. Controlled studies are being planned or conducted to substantiate the benefit of IVIg in neurodegenerative disorders. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 55 TC 9 Z9 9 U1 1 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD SEP PY 2006 VL 253 SU 5 BP 25 EP 32 DI 10.1007/s00415-006-5004-0 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 093UV UT WOS:000241196700005 ER PT J AU Rucker, JC Sheliga, BM FitzGibbon, EJ Miles, FA Leigh, RJ AF Rucker, Janet C. Sheliga, Boris M. FitzGibbon, Edmond J. Miles, Frederick A. Leigh, R. John TI Contrast sensitivity, first-order motion and initial ocular following in demyelinating optic neuropathy SO JOURNAL OF NEUROLOGY LA English DT Article DE optic neuritis; multiple sclerosis; saccades; pursuit ID NEURITIS TREATMENT TRIAL; VERGENCE EYE-MOVEMENTS; MULTIPLE-SCLEROSIS; BINOCULAR DISPARITY; RESPONSE FUNCTION; EVOKED-RESPONSES; VISUAL FUNCTION; HUMANS; DEPENDENCE; MONKEY AB The ocular following response (OFR) is a measure of motion vision elicited at ultra-short latencies by sudden movement of a large visual stimulus. We compared the OFR to vertical sinusoidal gratings (spatial frequency 0.153 cycles/degrees or 0.458 cycles/degrees) of each eye in a subject with evidence of left optic nerve demyelination due to multiple sclerosis (MS). The subject showed substantial differences in vision measured with stationary low-contrast Sloan letters (20/63 OD and 20/200 OS at 2.5% contrast) and the Lanthony Desaturated 15-hue color test (Color Confusion Index 1.11 OD and 2.14 OS). Compared with controls, all of the subject's OFR to increasing contrast showed a higher threshold. The OFR of each of the subject's eyes were similar for the 0.153 cycles/degrees stimulus, and psychophysical measurements of his ability to detect these moving gratings were also similar for each eye. However, with the 0.458 cycles/degrees stimulus, the subject's OFR was asymmetric and the affected eye showed decreased responses (smaller slope constant as estimated by the Naka-Rushton equation). These results suggest that, in this case, optic neuritis caused a selective deficit that affected parvocellular pathways mediating higher spatial frequencies, lower-contrast, and color vision, but spared the field-holding mechanism underlying the OFR to lower spatial frequencies. The OFR may provide a useful method to study motion vision in individuals with disorders affecting anterior visual pathways. C1 Univ Hosp, Dept Neurol, Cleveland, OH 44106 USA. Vet Affairs Med Ctr, Cleveland, OH USA. Case Western Reserve Univ, Univ Hosp, Cleveland, OH USA. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Leigh, RJ (reprint author), Univ Hosp, Dept Neurol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM rjl4@case.edu FU Intramural NIH HHS [Z01 EY000153-24]; NEI NIH HHS [EY06717, R01 EY006717] NR 36 TC 5 Z9 7 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD SEP PY 2006 VL 253 IS 9 BP 1203 EP 1209 DI 10.1007/s00415-006-0200-5 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 092QT UT WOS:000241113100013 PM 16649097 ER PT J AU Plaza, A Bewley, CA AF Plaza, Alberto Bewley, Carole A. TI Largamides A-H, unusual cyclic peptides from the marine cyanobacterium Oscillatoria sp. SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CONSTITUENT AMINO-ACIDS; COUPLING-CONSTANTS; ABSOLUTE-CONFIGURATION; CHYMOTRYPSIN INHIBITOR; NATURAL-PRODUCTS; CYANOPEPTOLIN; LC/MS AB Seven new depsipeptides, termed largamides A-G (1-7), and one new cyclic peptide, largamide H ( 8), have been isolated from the marine cyanobacterium Oscillatoria sp. Their structures were determined by NMR and ESI-MS techniques. The absolute configurations were assigned using LC-MS, chiral HPLC, and combined analysis of homonuclear and heteronuclear (2,3)J couplings, along with ROE data. Largamides, isolated from a single homogeneous cyanobacterial collection, represent three different structural classes of peptides. Largamides A-C (1-3) are characterized by the unusual occurrence of a senecioic acid unit, while largamides B ( 2) and C ( 3) possess in addition the rare 2-amino-5-(4'-hydroxyphenyl) pentanoic acid (Ahppa) and the novel 2-amino-6-(4'-hydroxyphenyl) hexanoic acid ( Ahpha), respectively. Largamides D-G (4-7) are the first 3-amino-6-hydroxy-2-piperidone acid (Ahp)-containing depsipeptides reported with the rare Ahppa unit. Largamide H (8) is a unique cyclic peptide displaying a new 2,5-dihydroxylated beta-amino acid moiety, a methoxylated derivative of Ahppa, and two residues of the nonstandard 2,3-dehydro-2-aminobutanoic acid (Dab). Largamides D-G (4-7) inhibited chymotrypsin with IC50 values ranging between 4 and 25 mu M. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU Intramural NIH HHS NR 21 TC 57 Z9 57 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD SEP 1 PY 2006 VL 71 IS 18 BP 6898 EP 6907 DI 10.1021/jo061044e PG 10 WC Chemistry, Organic SC Chemistry GA 077HO UT WOS:000240020100025 PM 16930043 ER PT J AU Glasker, S Tran, M Shively, SB Ikejin, B Lonser, RR Maxwell, PH Zhuang, Z Oldfield, EH Vortmeyer, AO AF Glaesker, S. Tran, M. G. B. Shively, S. B. Ikejin, B. Lonser, R. R. Maxwell, P. H. Zhuang, Z. Oldfield, E. H. Vortmeyer, A. O. TI Epididymal cystadenomas and epithelial tumourlets: effects of VHL deficiency on the human epididymis SO JOURNAL OF PATHOLOGY LA English DT Article DE von Hippel-Lindau disease; epididymis cystadenoma; tumour suppressor gene; hypoxia-inducible factor ID HIPPEL-LINDAU-DISEASE; HYPOXIA-INDUCIBLE FACTORS; PAPILLARY CYSTADENOMA; SUPPRESSOR GENE; CLEAR-CELL; BILATERAL PAPILLARY; RENAL-CARCINOMA; FACTORS HIF-1-ALPHA; PROTEIN; SAC AB Although epididymal cystadenomas (ECAs) are among the most frequent VHL disease-associated tumours, fundamental questions about their pathogenesis have remained unanswered. Classification of ECAs is controversial, and the cell of origin is unknown. It is also unknown whether ECAs - like other VHL disease-associated tumours - arise as a result of VHL gene inactivation, and whether ECAs exhibit subsequent activation of hypoxia-inducible factor HIF. Moreover, the morphological spectrum of earliest ECA formation is unknown. In a detailed molecular pathological analysis of a series of epididymides collected from VHL patients at autopsy, we found that ECAs are true neoplasms that arise secondary to inactivation of the wild-type copy of the VHL gene, followed by early and simultaneous activation of HIFI and HIF2 associated with up-regulation of downstream targets, including CAIX and GLUT-1. The observations also indicate that ECA formation evolves from a variety of microscopic epithelial tumourlets, and that these tumourlets are confined to the efferent ductular system. Although genetic and immunohistocheMical analysis of precursor structures consistently revealed VHL gene inactivation and activation of HIF in the precursor lesions, only a small subset appears to progress into frank cystadenoma. Thus, ECA tumorigenesis in VHL disease shares fundamental principles with tumorigenesis in other affected organ systems. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Neurochirurg Univ Klin, Freiburg, Germany. Univ London Imperial Coll Sci Technol & Med, Renal Sect, Hammersmith Hosp, London W12 0NN, England. George Washington Univ, Mol & Cellular Oncol, Inst Biomed Sci, Washington, DC USA. RP Vortmeyer, AO (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM vortmeyera@ninds.nih.gov RI Maxwell, Patrick/C-5557-2008 OI Maxwell, Patrick/0000-0002-0338-2679 FU Intramural NIH HHS NR 56 TC 21 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 2006 VL 210 IS 1 BP 32 EP 41 DI 10.1002/path.2029 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 077OZ UT WOS:000240040800006 PM 16841375 ER PT J AU Godwin, SC Shawker, T Chang, B Kaler, SG AF Godwin, Sarah C. Shawker, Thomas Chang, Benjamin Kaler, Stephen G. TI Brachial artery aneurysms in Menkes disease SO JOURNAL OF PEDIATRICS LA English DT Article ID CANDIDATE GENE; PATIENT; PROTEIN; ENCODES AB Generalized vascular tortuosity caused by deficiency of the copper enzyme lysyl oxidase is frequently noted in Menkes disease, but reported examples of peripheral aneurysms are rare. We describe bilateral brachial artery aneurysms in a 10-month-old infant with classical Menkes disease. C1 NICHHD, Unit Pediat Genet, Lab Clin Genet, Dept Diagnost Imaging,Clin Ctr,NIH, Bethesda, MD 20892 USA. Univ Penn, Childrens Hosp Philadelphia, Dept Plast Surg, Philadelphia, PA 19104 USA. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Lab Clin Genet, Dept Diagnost Imaging,Clin Ctr,NIH, Bldg 10,Room 5-2571,10 Ctr Dr MSC 1832, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov NR 17 TC 21 Z9 23 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2006 VL 149 IS 3 BP 412 EP 415 DI 10.1016/j.jpeds.2006.05.041 PG 4 WC Pediatrics SC Pediatrics GA 085OB UT WOS:000240612300029 PM 16939759 ER PT J AU Moody, TW Sun, LC Mantey, SA Pradhan, T Mackey, LV Gonzales, N Fuselier, JA Coy, DH Jensen, RT AF Moody, Terry W. Sun, Li-Chun Mantey, Samuel A. Pradhan, Tapas Mackey, L. Vienna Gonzales, Nieves Fuselier, Joseph A. Coy, David H. Jensen, Robert T. TI In vitro and in vivo antitumor effects of cytotoxic camptothecin-bombesin conjugates are mediated by specific interaction with cellular bombesin receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTRIN-RELEASING-PEPTIDE; LUNG-CANCER; MESSENGER-RNA; SOMATOSTATIN; GROWTH; ANALOGS; CELLS; SCINTIGRAPHY; EXPRESSION; CARCINOMA AB Most human tumors overexpress or ectopically express peptide hormone/ neurotransmitter receptors, which are being increasingly studied as a means to selectively deliver cytotoxic agents. Although a number of peptide ligand-constructs demonstrate tumor cytotoxicity, the role of specific tumoral receptor interaction in its mediation is unclear. To address this question, we synthesized camptothecin ( CPT) bombesin ( Bn) analogs, in which CPT was coupled via a novel carbamate linker, L2 [ N-( N-methylamino-ethyl)-glycine carbamate], that were chemically similar but differed markedly in their potency/affinity for human Bn receptors. We then examined their ability to interact with Bn receptors and cause in vitro and in vivo tumor cytotoxicity. CPT-L2-[D-Tyr(6), beta-Ala(11), D-Phe(13), Nle(14)] Bn ( 6-14) ( BA3) bound with high affinity and had high potency for all three human Bn receptor subtypes, whereas CPT-L2-[ D-Tyr(6), beta-Ala(11), D-Phe(13), Nle(14)] Bn ( 6-14) [ D-Phe-CPT-L2-BA3] had > 1400-fold lower affinity/potency. I-125-CPT-L2-BA3 but not I-125-D-Phe-CPT-L2-BA3 was internalized by Bn receptor subtype-containing cells. CPT-L2- BA3 displayed significantly more cytotoxicity than D-Phe-CPT-L2-BA3 toward NCI-H1299 lung cancer cells in both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and clonogenic assays and more potently inhibited H1299 xenograft growth in nude mice. CPT-L2- BA3 was also metabolically more stable than its parent peptide and inhibited growth of a number of other tumor cell lines in vitro and in vivo. These results demonstrate that specific tumoral receptor interaction is important in mediating the ability of peptide ligand-cytotoxic constructs to cause cytotoxicity. Because many tumors overexpress Bn receptors, these results also demonstrate that CPT-L2- BA3 will be a useful agent for delivering receptor-mediated cytotoxicity to many different human tumors. C1 NCI, US Dept HHS, NIH, Off Director,Ctr Canc Res, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Tulane Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA USA. RP Moody, TW (reprint author), NCI, US Dept HHS, NIH, Off Director,Ctr Canc Res, Bldg 31,Room 4A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM moodyt@mail.nih.gov FU Intramural NIH HHS NR 40 TC 28 Z9 31 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2006 VL 318 IS 3 BP 1265 EP 1272 DI 10.1124/jpet.106.104141 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075IT UT WOS:000239878900039 PM 16766720 ER PT J AU Chen, C Meng, LH Ma, XC Krausz, KW Pommier, Y Idle, JR Gonzalez, FJ AF Chen, Chi Meng, Linghua Ma, Xiaochao Krausz, Kristopher W. Pommier, Yves Idle, Jeffrey R. Gonzalez, Frank J. TI Urinary metabolite profiling reveals CYP1A2-mediated metabolism of NSC686288 (aminoflavone) SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PHENACETIN O-DEETHYLASE; AROMATIC-AMINES; ANTITUMOR AGENT; HETEROCYCLIC AMINES; MASS-SPECTROMETRY; LIVER-MICROSOMES; BREAST-CANCER; CYP1A2; MICE; ACTIVATION AB NSC686288 [aminoflavone (AF)], a candidate chemotherapeutic agent, possesses a unique antiproliferative profile against tumor cells. Metabolic bioactivation of AF by drug-metabolizing enzymes, especially CYP1A monooxygenases, has been implicated as an underlying mechanism for its selective cytotoxicity in several cell culture-based studies. However, in vivo metabolism of AF has not been investigated in detail. In this study, the structural identities of 13 AF metabolites ( 12 of which are novel) in mouse urine or from microsomal incubations, including three monohydroxy-AFs, two dihydroxy-AFs and their sulfate and glucuronide conjugates, as well as one N-glucuronide, were determined by accurate mass measurements and liquid chromatography-tandem mass spectrometry fragmentation patterns, and a comprehensive map of the AF metabolic pathways was constructed. Significant differences between wild-type and Cyp1a2-null mice, within the relative composition of urinary metabolites of AF, demonstrated that CYP1A2-mediated regioselective oxidation was a major contributor to the metabolism of AF. Comparisons between wild-type and CYP1A2-humanized mice further revealed interspecies differences in CYP1A2-mediated catalytic activity. Incubation of AF with liver microsomes from all three mouse lines and with pooled human liver microsomes confirmed the observations from urinary metabolite profiling. Results from enzyme kinetic analysis further indicated that in addition to CYP1A P450s, CYP2C P450s may also play some role in the metabolism of AF. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Charles Univ, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Chen, Chi/B-4618-2008; OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005562-18] NR 29 TC 46 Z9 46 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2006 VL 318 IS 3 BP 1330 EP 1342 DI 10.1124/jpet.106.105213 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075IT UT WOS:000239878900048 PM 16775196 ER PT J AU Zmudzka, BZ Hearing, VJ Beer, JZ AF Zmudzka, Barbara Z. Hearing, Vincent J. Beer, Janusz Z. TI Photobiologic role of melanin distribution in the epidermis SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Letter ID SKIN C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zmudzka, BZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM barbara.zmudzka@fda.hhs.gov NR 3 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD SEP 1 PY 2006 VL 84 IS 3 BP 231 EP 231 DI 10.1016/j.jphotobiol.2006.05.008 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 079YA UT WOS:000240212600010 PM 16857378 ER PT J AU Woodard, GE Zhao, J Rosado, JA AF Woodard, G. E. Zhao, J. Rosado, J. A. TI Inhibitory effect of Ca2+ on ATP-mediated stimulation of NPR-A-coupled guanylyl cyclase in renal glomeruli from spontaneously hypertensive and normotensive rats SO JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE ANP(1-28); NPR-A; ATP Ca2+; renal glomeruli; hypertension; cGMP production ID NATRIURETIC-PEPTIDE RECEPTOR; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; DOWN-REGULATION; CGMP PRODUCTION; ACTIVATION; CALCIUM; BINDING; PROTEINS; DISEASES AB Atrial natriuretic peptide (ANP) regulates blood pressure mainly through the occupation of the guanylyl cyclase-coupled receptor NPR-A, which requires ATP interaction for maximal activation. This study investigates the effect of extracellular Ca2+ on ATP-mediated regulation of NPR-A-coupled guanylyl cyclase activity in glomerular membranes from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). ATP induced a significant increase in basal and ANP(1.28)-stimulated guanylyl cyclase activity that was greater in SHR than in WKY. Extracellular Ca2+ inhibited ATP-stimulated guanylyl cyclase activity in a concentration-dependent manner, but did not modify basal and ANP(1-28)-stimulated guanylyl cyclase activity. In the presence of ATP, NPR-A showed higher affinity for ANP(1-28) and lower Bmax. Call did not modify NPR-A-ANP(1-28) binding properties. The different effects of extracellular Ca2+ on ANP(1-28)- or ATP-mediated guanylyl cyclase activation suggest that these events are differentially regulated. Addition of extracellular Ca2+ induced similar effects in hypertensive and normotensive rats, suggesting that it is not responsible for the elevated cGMP production observed in SHR. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England. Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIDDKD, NIH, 10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. EM GeoffreyW@intra.niddk.nih.gov RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 41 TC 0 Z9 0 U1 0 U2 0 PU POLISH PHYSIOLOGICAL SOC PI GRZEGORZECKA PA JAGIELLONIAN UNIV SCHOOL MED, INST PHYSIOLOGY, 31-531 KRAKOW, 16 GRZEGORZECKA, POLAND SN 0867-5910 J9 J PHYSIOL PHARMACOL JI J. Physiol. Pharmacol. PD SEP PY 2006 VL 57 IS 3 BP 359 EP 373 PG 15 WC Physiology SC Physiology GA 090BZ UT WOS:000240926900004 PM 17033090 ER PT J AU McBain, CJ Traynelis, SF AF McBain, Chris J. Traynelis, Stephen F. TI Malevolent lurkers no more: NMDA receptors come of age SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID D-ASPARTATE RECEPTORS; MOUSE CENTRAL NEURONS; RAT HIPPOCAMPUS; RESPONSES C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. RP McBain, CJ (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. EM strayne@emory.edu NR 11 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2006 VL 575 IS 2 BP 317 EP 318 DI 10.1113/jphysiol.2006.114629 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 077DD UT WOS:000240007000001 PM 16809360 ER PT J AU Chuaychoo, B Lee, MG Kollarik, M Pullmann, R Undem, BJ AF Chuaychoo, Benjamas Lee, Min-Goo Kollarik, Marian Pullmann, Rudolf, Jr. Undem, Bradley J. TI Evidence for both adenosine A(1) and A(2A) receptors activating single vagal sensory C-fibres in guinea pig lungs SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SMOOTH-MUSCLE CELLS; INDUCED BRONCHOCONSTRICTION; ANESTHETIZED RATS; ASTHMATIC SUBJECTS; INHALED ADENOSINE; AIRWAYS; 5'-MONOPHOSPHATE; A1-ADENOSINE; CONTRACTION; MECHANISM AB We addressed the hypothesis that single vagal afferent C-fibres can be stimulated via either the adenosine A(1) or A(2A) receptor subtypes. The effect of adenosine on the nerve terminals of vagal sensory nerve subtypes was evaluated in an ex vivo perfused guinea pig lung preparation using extracellular recording techniques. Adenosine (10 mu m) consistently evoked action potential discharge in lung C-fibre terminals arising from the nodose ganglia, but failed to evoke action potential discharge in most jugular ganglion C-fibres. Adenosine also failed to activate stretch-sensitive nodose A-fibres in the lungs. The selective A(1) antagonist DPCPX (0.1 mu m) or the selective A(2A) antagonist SCH 58261 (0.1 mu m) partially inhibited the nodose C-fibre activation by adenosine, and the combination of both antagonists almost completely inhibited the response. The adenosine-induced action potential discharge in nodose C-fibres was mimicked by either the selective A(1) agonist CCPA (1 mu m) or the selective A(2A) agonist CGS 21680 (1 mu m). Single cell PCR techniques revealed that adenosine A(1) and A(2A) receptor mRNA was expressed in individual nodose neurons retrogradely labelled from the lungs. The gramicidin-perforated patch clamp technique on neurons retrogradely labelled from the lungs was employed to study the functional consequence of adenosine receptor agonists directly on neuronal membrane properties. Both the selective A(1) agonist CCPA (1 mu m) and the selective A(2A) agonist CGS 21680 (1 mu m) depolarized the airway-specific, capsaicin-sensitive, nodose neurons to action potential threshold. The data support the hypothesis that adenosine selectively depolarizes vagal nodose C-fibre terminals in the lungs to action potential threshold, by stimulation of both adenosine A(1) and A(2A) receptor subtypes located in the neuronal membrane. C1 Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. RP Undem, BJ (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM bundem@jhmi.edu NR 38 TC 43 Z9 48 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2006 VL 575 IS 2 BP 481 EP 490 DI 10.1113/j.physiol.2006.109371 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 077DD UT WOS:000240007000021 PM 16793905 ER PT J AU Lu, T Ye, D Wang, XL Seubert, JM Graves, JP Bradbury, JA Zeldin, DC Lee, HC AF Lu, Tong Ye, Dan Wang, Xiaoli Seubert, John M. Graves, Joan P. Bradbury, J. Alyce Zeldin, Darryl C. Lee, Hon-Chi TI Cardiac and vascular K(ATP) channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PIG VENTRICULAR MYOCYTES; ARACHIDONIC-ACID; GUINEA-PIG; SMOOTH-MUSCLE; 11,12-EPOXYEICOSATRIENOIC ACID; POTASSIUM CHANNELS; CORONARY-ARTERIES; ANTISENSE OLIGONUCLEOTIDES; HYPERPOLARIZING FACTOR; MOLECULAR-CLONING AB We have reported that epoxyeicosatrienoic acids (EETs), the cytochrome P450 (CYP) epoxygenase metabolites of arachidonic acid (AA), are potent sarcolemmal ATP-sensitive K(+) (K(ATP)) channel activators. However, activation of cardiac and vascular K(ATP) channels by endogenously produced EETs under physiological intracellular conditions has not been demonstrated and direct comparison of the mechanisms whereby EETs activate the K(ATP) channels in cardiac myocytes versus vascular smooth muscle cells has not been made. In this study, we examined the effects of AA on K(ATP) channels in freshly isolated cardiac myocytes from rats, wild-type (WT) and transgenic mice overexpressing CYP2J2 cDNA, and mesenteric arterial smooth muscle cells from rats. We also compared the activation of cardiac and vascular K(ATP) channels by extracellularly and intracellularly applied 11,12-EET. We found that 1 mu m AA enhanced K(ATP) channel activities in both cardiac and vascular smooth muscle cells, and the AA effects were inhibited by preincubation with CYP epoxygenase inhibitors. Baseline cardiac K(ATP) current densities in CYP2J2 transgenic mice were 190% higher than those of WT mice, and both were reduced to similar levels by CYP epoxygenase inhibition. Western blot analysis showed that expression of Kir6.2 and SUR2A was similar between WT and CYP2J2 transgenic hearts. 11,12-EET (5 mu m) applied intracellularly enhanced the K(ATP) currents by 850% in cardiac myocytes, but had no effect in vascular smooth muscle cells. In contrast, 11,12-EET (5 mu m) applied extracellularly increased K(ATP) currents by 520% in mesenteric arterial smooth muscle cells, but by only 209% in cardiac myocytes. Preincubation with 100 mu m m-iodobenzylguanidine or 5 mu m myristoylated PKI amide did not alter the activation of cardiac K(ATP) channels by 5 mu m 11,12-EET, but significantly inhibited activation of vascular K(ATP) channels. Moreover, EET only enhanced the inward component of cardiac K(ATP) currents, but activated both the inward and outward components of vascular K(ATP) currents. Our results indicate that endogenously derived CYP metabolites of AA potently activate cardiac and vascular K(ATP) channels. EETs regulate cardiac electrophysiology and vascular tone by K(ATP) channel activation, albeit through different mechanisms: the cardiac K(ATP) channels are directly activated by EETs, whereas activation of the vascular K(ATP) channels by EETs is protein kinase A dependent. C1 Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA. Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Lee, HC (reprint author), Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA. EM lee.honchi@mayo.edu RI Lu, Tong/A-7745-2009 OI Lu, Tong/0000-0002-2393-7643 FU NHLBI NIH HHS [R56 HL074180, HL-63754, HL-74180, R01 HL063754, R01 HL074180] NR 70 TC 52 Z9 53 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP 1 PY 2006 VL 575 IS 2 BP 627 EP 644 DI 10.1113/jphysiol.2006.113985 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 077DD UT WOS:000240007000031 PM 16793897 ER PT J AU Zhou, M Prieto, DA Lucas, DA Chan, KC Issaq, HJ Veenstra, TD Conrads, TP AF Zhou, Ming Prieto, DaRue A. Lucas, David A. Chan, King C. Issaq, Haleem J. Veenstra, Timothy D. Conrads, Thomas P. TI Identification of the SELDI ProteinChip human serum retentate by microcapillary liquid chromatography-tandem mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE SELDI; biomarker; serum proteomics; multidimensional fractionation; mass spectrometry ID OVARIAN-CANCER; PROSTATE-CANCER; BREAST-CANCER; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; PROTEOMIC PATTERNS; BINDING GLOBULIN; MYOCARDIAL-INFARCTION; PROGNOSTIC MARKER; LUNG-CANCER AB Surface-enhanced laser desorption/ionization (SELDI) time-of-flight (TOF) mass spectrometry ( MS) has been widely applied for conducting biomarker research with the goal of discovering patterns of proteins and/or peptides from biological samples that reflect disease status. Many diseases, ranging from cancers of the colon, breast, and prostate to Alzheimer's disease, have been studied through serum protein profiling using SELDI-based methods. Although the results from SELDI-based diagnostic studies have generated a great deal of excitement and skepticism alike, the basis of the molecular identities of the features that underpin the diagnostic potential of the mass spectra is still largely unexplored. A detailed investigation has been undertaken to identify the compliment of serum proteins that bind to the commonly used weak cation exchange (WCX-2) SELDI protein chip. Following incubation and washing of a standard serum sample on the WCX-2 sorbent, proteins were harvested, digested with trypsin, fractionated by strong cation exchange liquid chromatography (LC), and subsequently analyzed by microcapillary reversed-phase LC coupled online with an ion-trap mass spectrometer. This analysis resulted in the identification of 383 unique proteins in the WCX-2 serum retentate. Among the proteins identified, 50 (13%) are documented clinical biomarkers with 36 of these (72%) identified from multiple peptides. C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, Ft Detrick, MD 21702 USA. RP Conrads, TP (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Lab Proteom & Analyt Technol, POB B, Ft Detrick, MD 21702 USA. EM conrads@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 91 TC 13 Z9 14 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP 1 PY 2006 VL 5 IS 9 BP 2207 EP 2216 DI 10.1021/pr060061h PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 079TL UT WOS:000240200700017 PM 16944932 ER PT J AU Abu-Asab, M Chaouchi, M Amri, H AF Abu-Asab, Mones Chaouchi, Mohamed Amri, Hakima TI Phyloproteomics: What phylogenetic analysis reveals about serum proteomics SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE cancer; dichotomous development; mass spectrometry; phylogenetics; phyloproteomics; proteomics; serum; transitional clades ID LASER-DESORPTION/IONIZATION-TIME; FLIGHT-MASS-SPECTROMETRY; OVARIAN-CANCER DETECTION; PROSTATE-CANCER; PATTERNS; CARCINOGENESIS; PATHWAYS; MEN AB Phyloproteomics is a novel analytical tool that solves the issue of comparability between proteomic analyses, utilizes a total spectrum-parsing algorithm, and produces biologically meaningful classification of specimens. Phyloproteomics employs two algorithms: a new parsing algorithm (UNIPAL) and a phylogenetic algorithm (MIX). By outgroup comparison, the parsing algorithm identifies novel or vanished MS peaks and peaks signifying up or down regulated proteins and scores them as derived or ancestral. The phylogenetic algorithm uses the latter scores to produce a biologically meaningful classification of the specimens. C1 NCI, Pathol Lab, NIH, Bethesda, MD USA. Natl Ocean & Atmospher Adm, Natl Ocean Serv, CO OPS Informat Syst Div, Silver Spring, MD USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. RP Abu-Asab, M (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD USA. EM mones@mail.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 24 TC 10 Z9 11 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP 1 PY 2006 VL 5 IS 9 BP 2236 EP 2240 DI 10.1021/pr0504485 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 079TL UT WOS:000240200700020 PM 16944935 ER PT J AU Go, EP Wikoff, WR Shen, ZX O'Maille, G Morita, H Conrads, TP Nordstrom, A Trauger, SA Uritboonthai, W Lucas, DA Chan, KC Veenstra, TD Lewicki, H Oldstone, MB Schneemann, A Siuzdak, G AF Go, Eden P. Wikoff, William R. Shen, Zhouxin O'Maille, Grace Morita, Hirotoshi Conrads, Thomas P. Nordstrom, Anders Trauger, Sunia A. Uritboonthai, Wilasinee Lucas, David A. Chan, King C. Veenstra, Timothy D. Lewicki, Hanna Oldstone, Michael B. Schneemann, Anette Siuzdak, Gary TI Mass spectrometry reveals specific and global molecular transformations during viral infection SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE virus; protein regulation; viral infection; metabolites; isotope labeling; mass spectrometry ID FLOCK HOUSE VIRUS; CATALYZED O-16-TO-O-18 EXCHANGE; BLACK BEETLE VIRUS; TIME TAG APPROACH; QUANTITATIVE PROTEOMICS; ACCURATE MASS; SACCHAROMYCES-CEREVISIAE; ANTIVIRAL RESPONSE; GENE-EXPRESSION; ANIMAL VIRUS AB Mass spectrometry analysis was used to target three different aspects of the viral infection process: the expression kinetics of viral proteins, changes in the expression levels of cellular proteins, and the changes in cellular metabolites in response to viral infection. The combination of these methods represents a new, more comprehensive approach to the study of viral infection revealing the complexity of these events within the infected cell. The proteins associated with measles virus (MV) infection of human HeLa cells were measured using a label-free approach. On the other hand, the regulation of cellular and Flock House Virus ( FHV) proteins in response to FHV infection of Drosophila cells was monitored using stable isotope labeling. Three complementary techniques were used to monitor changes in viral protein expression in the cell and host protein expression. A total of 1500 host proteins was identified and quantified, of which over 200 proteins were either up- or down- regulated in response to viral infection, such as the up- regulation of the Drosophila apoptotic croquemort protein, and the down- regulation of proteins that inhibited cell death. These analyses also demonstrated the up-regulation of viral proteins functioning in replication, inhibition of RNA interference, viral assembly, and RNA encapsidation. Over 1000 unique metabolites were also observed with significant changes in over 30, such as the down-regulated cellular phospholipids possibly reflecting the initial events in cell death and viral release. Overall, the cellular transformation that occurs upon viral infection is a process involving hundreds of proteins and metabolites, many of which are structurally and functionally uncharacterized. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Ctr Mass Spectrometry, La Jolla, CA 92037 USA. Mass Consortium Corp, San Diego, CA 92019 USA. SAIC Frederick Inc, Natl Canc Inst, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Infectol, La Jolla, CA 92037 USA. RP Schneemann, A (reprint author), Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. EM aschneem@scripps.edu; siuzdak@scripps.edu FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [R01 AI036222, AI036222]; NIGMS NIH HHS [R01 GM055775, R01 GM055775-02, GM55775] NR 59 TC 37 Z9 40 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP 1 PY 2006 VL 5 IS 9 BP 2405 EP 2416 DI 10.1021/pr060215t PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 079TL UT WOS:000240200700038 PM 16944953 ER PT J AU Vitiello, MV Foley, DJ Bliwise, DL Ancoli-Israel, S Monjan, AA Walsh, JK AF Vitiello, M. V. Foley, D. J. Bliwise, D. L. Ancoli-Israel, S. Monjan, A. A. Walsh, J. K. TI Frequent napping in older adults is associated with excessive daytime sleepiness, depression, pain and nocturia SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 18th Congress of the European-Sleep-Research-Society CY SEP 12-16, 2006 CL Innsbruck, AUSTRIA SP European Sleep Res Soc C1 Univ Washington, Seattle, WA 98195 USA. SAMHSA, Rockville, MD USA. Emory Univ, Atlanta, GA 30322 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NIA, Bethesda, MD 20892 USA. St Lukes Hosp, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD SEP PY 2006 VL 15 SU 1 BP 130 EP 130 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 076NW UT WOS:000239966000345 ER PT J AU O'Brien, SM Kupper, LL Dunson, DB AF O'Brien, SM Kupper, LL Dunson, DB TI Performance of tests of association in misspecified generalized linear models SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE asymptotic power; degrees of freedom; generalized linear model; model misspecification; parsimony; test of association ID MEASUREMENT ERROR; SCORE TESTS; EFFICIENCY AB We examine the effects of modelling errors, such as underfitting and overfitting, on the asymptotic power of tests of association between an explanatory variable x and an outcome in the setting of generalized linear models. The regression function for x is approximated by a polynomial or another simple function, and a chi-square statistic is used to test whether the coefficients of the approximation are simultaneously equal to zero. Adding terms to the approximation increases asymptotic power if and only if the fit of the model increases by a certain quantifiable amount. Although a high degree of freedom approximation offers robustness to the shape of the unknown regression function, a low degree of freedom approximation can yield much higher asymptotic power even when the approximation is very poor. In practice, it is useful to compute the power of competing test statistics across the range of alternatives that are plausible a priori. This approach is illustrated through an application in epidemiology. (c) 2005 Elsevier B.V. All rights reserved. C1 Duke CLin Res Inst, Dept Biostat & Bioinformat, Durham, NC 27715 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIEHS, Biostat Branch MD A3 03, Res Triangle Pk, NC 27709 USA. RP O'Brien, SM (reprint author), Duke CLin Res Inst, Dept Biostat & Bioinformat, POB 17969, Durham, NC 27715 USA. EM obric027@dcri.duke.edu; kupper@bios.unc.edu; dunson1@niehs.nih.gov RI O'Brien, Sean/H-6268-2013 NR 11 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD SEP 1 PY 2006 VL 136 IS 9 BP 3090 EP 3100 DI 10.1016/j.jspi.2004.12.004 PG 11 WC Statistics & Probability SC Mathematics GA 053LQ UT WOS:000238307000012 ER PT J AU Vexler, A AF Vexler, A TI Guaranteed testing for epidemic changes of a linear regression model SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE change point; CUSUM statistics; epidemic alternative; invariant statistics; martingale structure; maximum likelihood; segmented linear regression; Shiryayev-Roberts statistics AB The objective of this paper is to propose and examine a class of generalized maximum likelihood asymptotic power one tests for detection of various types of changes in a linear regression model. The proposed retrospective tests are based on martingales structures Shiryayev-Roberts statistics. This approach is widely known in a sequential analysis of change point problems as an optimal method of detecting a change in distribution. Guaranteed non-asymptotic upper bounds for the significance levels of the considered tests are presented. Simulated data sets are used to demonstrate that the proposed tests can give good results in practice. (c) 2005 Elsevier B.V. All rights reserved. C1 Hebrew Univ Jerusalem, IL-91905 Jerusalem, Israel. RP Vexler, A (reprint author), NICHHD, US Dept HHS, NIH, 6100 Execut Blvd,Rm 7B05L, Rockville, MD 20852 USA. EM vexlera@mail.nih.gov NR 23 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD SEP 1 PY 2006 VL 136 IS 9 BP 3101 EP 3120 DI 10.1016/j.jspi.2004.11.010 PG 20 WC Statistics & Probability SC Mathematics GA 053LQ UT WOS:000238307000013 ER PT J AU Guyer, AE Kaufman, J Hodgdon, HB Masten, CL Jazbec, S Pine, DS Ernst, M AF Guyer, Amanda E. Kaufman, Joan Hodgdon, Hilary B. Masten, Carrie L. Jazbec, Sandra Pine, Daniel S. Ernst, Monique TI Behavioral alterations in reward system function: The role of childhood maltreatment and psychopathology SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; decision-making; risk-taking; motivation; depression ID POSTTRAUMATIC-STRESS-DISORDER; DECISION-MAKING; DEPRESSION; EXPERIENCE; RESPONSES; CHILDREN; RISK; NEUROBIOLOGY; ADOLESCENTS; AMYGDALA AB Objective: To examine in children the influence of maltreatment and associated psychiatric sequelae on behavioral responses to reward stimuli. Method: A computerized two-choice decision-making task involving probabilistic monetary gains was used to probe elemental processes of goal-directed actions. Using different risk contingencies, the authors examined decision-making, expectations of outcomes, and affective responses to rewards in 38 maltreated children and 21 demographically matched controls (8-14 years old). Results: Maltreated children selected risk options faster than controls; however, whereas controls responded more quickly as the chance of winning increased, maltreated children did not vary in response speed as a function of the likelihood of winning. When choosing between high- and low-risk options, maltreated children with depressive disorders more frequently selected safe over risky choices than did controls. No group differences emerged in self-report ratings of positive or negative reactions to winning or not winning, respectively. Conclusions: This initial experimental study of responses to reward lays the groundwork for subsequent research on neurodevelopmental aspects of reward processes in relationship to maltreatment and psychopathology. Clinical applications of these data may be relevant for developing treatment plans for maltreated children, particularly those with depression. C1 NIMH, Mood & Anxiety Program, Emot Dev & Affect Neurosci Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Zurich, Dept Psychol, CH-8006 Zurich, Switzerland. RP Guyer, AE (reprint author), NIMH, Mood & Anxiety Program, Emot Dev & Affect Neurosci Branch, NIH, 15K N Dr,Room 208,MSC 2670, Bethesda, MD 20892 USA. EM amandaguyer@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [1R01MH65519-01] NR 44 TC 46 Z9 46 U1 6 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2006 VL 45 IS 9 BP 1059 EP 1067 DI 10.1097/01.chi.0000227882.50404.11 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 078NO UT WOS:000240110700005 PM 16926613 ER PT J AU Bruno, DA Xu, H Hale, D D Kirk, A AF Bruno, David A. Xu, He Hale, Douglas D Kirk, Allan TI xuALG-A polyclonal antibody that depletes memory T-cells SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 NIDDK, DHHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S92 EP S92 DI 10.1016/j.jamcollsurg.2006.05.241 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800199 ER PT J AU Dhanireddy, KK Bruno, DA Zhang, X Leopardi, FV Johnson, LB Kirk, AD AF Dhanireddy, Kiran K. Bruno, David A. Zhang, Xiaojie Leopardi, Frank V. Johnson, Lynt B. Kirk, Allan D. TI Alefacept (LFA3-1g), portal venous donor specific transfusion (PVDST), and sirolimus prolong renal allograft survival in non-human primates SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 NIDDK, DHHS, NIH, Transplantat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S92 EP S92 DI 10.1016/j.jamcollsurg.2006.05.240 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800198 ER PT J AU Dhanireddy, KK Bruno, DA Shiva, S Leopardi, FV Zhang, X Gladwin, M Kirk, AD AF Dhanireddy, Kiran K. Bruno, David A. Shiva, Sruti Leopardi, Frank V. Zhang, Xiaojie Gladwin, Mark Kirk, Allan D. TI Nitrite, a hypoxia selective nitric oxide donor, limits renal ischemia-reperfusion injury in non-human primates SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 NIDDK, US Dept HHS, NIH, Transplanatat Branch, Bethesda, MD USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S31 EP S31 DI 10.1016/j.jamcollsurg.2006.05.076 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800050 ER PT J AU Tsai, S Mixon, A Farid, S Dudly, M Topalian, S AF Tsai, Susan Mixon, Arnold Farid, Shawn Dudly, Mark Topalian, Suzanne TI Co-stimulatory signals upregulate PD-1 expression on human T lymphocytes: Implications for cancer immunotherapy SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 61st Annual Session of the Surgical Forum 2006 Clinical Congress CY OCT 08-12, 2006 CL Chicago, IL C1 NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2006 VL 203 IS 3 SU S BP S81 EP S81 DI 10.1016/j.jamcollsurg.2006.05.211 PG 1 WC Surgery SC Surgery GA 082SF UT WOS:000240406800171 ER PT J AU Guenther, PM Dodd, KW Reedy, J Krebs-Smith, SM AF Guenther, Patricia M. Dodd, Kevin W. Reedy, Jill Krebs-Smith, Susan M. TI Most Americans eat much less than recommended amounts of fruits and vegetables SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID INTAKE DISTRIBUTIONS AB Objective To estimate the proportions of the population meeting recommendations for fruit and vegetable intake, we first estimated the usual intake distributions of total fruits. and vegetables and then compared the results to the 5 A Day recommendation and to the recommendations for fruits and vegetables combined, found in the new US Department of Agriculture food guide, MyPyramid. Design/subjects The primary dataset was created from one 24-hour recall from each of 8,070 respondents in the 1999-2000 National Health and Nutrition Examination Survey. Variances were estimated using one or two 24-hour recalls from 14,963 respondents in the 1994-1996 Continuing Survey of Food Intakes by Individuals. Statistical analysis The statistical method developed at Iowa State University was used for estimating distributions of usual intake of dietary components that are consumed daily. It was modified to allow the adjustment of heterogeneous within-person variances using an external estimate of heterogeneity. Results In 1999-2000, only 40% of Americans ate an average of five or more 1/2-cup servings of fruits and vegetables per day. The proportions of sex-age groups meeting the new US Department of Agriculture recommendations ranged from 0.7% of boys aged 14 to 18 years, whose combined recommendation is 5 cups, to 48% of children aged 2 to 3 years, whose combined recommendation is 2 cups. Conclusions Americans need to consume more fruits and vegetables, especially dark green and orange vegetables and legumes. Nutritionists must help consumers realize that, for everyone older than age 3 years, the new recommendations for fruit and vegetable intakes are greater than the familiar five servings a day. C1 USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Guenther, PM (reprint author), USDA, Ctr Nutr Policy & Promot, 3101 Pk Ctr Dr,Ste 1034, Alexandria, VA 22302 USA. EM Patricia.Guenther@cnpp.usda.gov NR 28 TC 327 Z9 333 U1 2 U2 38 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2006 VL 106 IS 9 BP 1371 EP 1379 DI 10.1016/j.jada.2006.06.002 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 081MV UT WOS:000240322600015 PM 16963342 ER PT J AU Kaplan, RC Tirschwell, DL Longstreth, WT Manolio, TA Heckbert, SR LeValley, AJ Lefkowitz, D El-Saed, A Psaty, BM AF Kaplan, Robert C. Tirschwell, David L. Longstreth, W. T., Jr. Manolio, Teri A. Heckbert, Susan R. LeValley, Aaron J. Lefkowitz, David El-Saed, Aiman Psaty, Bruce M. TI Blood pressure level and outcomes in adults aged 65 and older with prior ischemic stroke SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE stroke; blood pressure; prognosis ID SECONDARY PREVENTION; CARDIOVASCULAR HEALTH; VASCULAR EVENTS; REDUCTION; RISK; ASSOCIATION; MORTALITY; ATENOLOL; THERAPY; DISEASE AB OBJECTIVES: To examine the association between blood pressure (BP) levels and long-term stroke outcomes in elderly stroke survivors. DESIGN: Observational study. SETTING: The Cardiovascular Health Study (CHS) of 5,888 community-dwelling adults. PARTICIPANTS: Two hundred fifty-four adults aged 65 and older (mean age 78.6) who sustained a nonfatal first ischemic stroke. MEASUREMENTS: BP levels assessed at prestroke and poststroke CHS visits were examined as predictors of stroke recurrence, coronary heart disease (CHD), combined vascular events (CVEs), and mortality. RESULTS: Higher poststroke BP level, assessed 261.6 days (mean) after stroke, was associated with higher risk of stroke recurrence over 5.4 years (mean) of follow-up. The multivariate-adjusted hazard ratio for stroke recurrence was 1.42 (95% confidence interval (CI)=1.03-1.99) per standard deviation (SD) of systolic BP (P=.04) and 1.39 (95% CI=1.01-1.91) per SD of diastolic BP (P=.04). Mortality was significantly greater in patients with low or high poststroke BP than in those with intermediate BP. Poststroke BP was not associated with risk of CHD or CVE, although further analyses suggested that high systolic BP predicted CHD and CVE in younger but not older subjects. Prestroke BP did not predict poststroke outcomes. CONCLUSION: In this observational study of adults aged 65 and older assessed approximately 8 months after stroke, low BP was associated with favorable risk of recurrent stroke, although high and low poststroke BP levels were associated with greater mortality. Long-term antihypertensive trials in older stroke survivors would increase knowledge about the benefits of lowering BP in this population. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. NHLBI, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27109 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Kaplan, RC (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Belfer Bldg,Room 1306C,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM rkaplan@aecom.yu.edu RI Kaplan, Robert/A-2526-2011 FU NHLBI NIH HHS [N01-HC-35129, N01 HC-15103, N01-HC-85079, N01-HC-85086, R01 HL43201]; NIA NIH HHS [5R01AG009556-08] NR 19 TC 11 Z9 12 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2006 VL 54 IS 9 BP 1309 EP 1316 DI 10.1111/j.1532-5415.2006.00838.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 081LN UT WOS:000240319200001 PM 16970636 ER PT J AU McNeill, AM Katz, R Girman, CJ Rosamond, WD Wagenknecht, LE Barzilay, JI Tracy, RP Savage, PJ Jackson, SA AF McNeill, Ann Marie Katz, Ronit Girman, Cynthia J. Rosamond, Wayne D. Wagenknecht, Lynne E. Barzilay, Joshua I. Tracy, Russell P. Savage, Peter J. Jackson, Sharon A. TI Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; cardiovascular diseases; epidemiology; metabolic syndrome ID CORONARY-HEART-DISEASE; CHOLESTEROL EDUCATION-PROGRAM; IMPAIRED FASTING GLUCOSE; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS; ALL-CAUSE; MORTALITY; RISK; DIAGNOSIS; ADULTS AB OBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD. DESIGN: Prospective cohort study. SETTING: Four field centers in U.S. communities. PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62% female, 14% black). MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (>= 3 of the following: large waist circumference (women > 88 cm, men > 102 cm), elevated triglycerides (>= 1.70 mmol/L), low high-density lipoprotein cholesterol (men < 1.04 mmol/L, women < 1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (>= 130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L). RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95% confidence interval (CI)=1.07-1.57), 0.94 (95% CI=0.73-1.21), and 1.40 (95% CI=1.12-1.76) for women and 1.35 (95% CI=1.10-1.66), 1.51 (95% CI=1.08-2.12), and 1.47 (95% CI=1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20% to 30% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16% to 46%) and an additional 9% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD. CONCLUSIONS: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. Merck Sharp & Dohme Ltd, Res Labs, Dept Epidemiol, West Point, PA 19486 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Kaiser Permanente, Div Endocrinol, Atlanta, GA USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Vermont, Coll Med, Lab Clin Biochem Res, Burlington, VT USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP McNeill, AM (reprint author), Univ N Carolina, Dept Epidemiol, 137 E Franklin St, Chapel Hill, NC 27514 USA. EM am_mcneill@alumni.unc.edu FU NHLBI NIH HHS [N01-HC-35129, 5-T32-HL07055, N01 HC-15103, N01-HC-85079, N01-HC-85086] NR 27 TC 95 Z9 99 U1 4 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2006 VL 54 IS 9 BP 1317 EP 1324 DI 10.1111/j.1532-5415.2006.00862.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 081LN UT WOS:000240319200002 PM 16970637 ER PT J AU Thorpe, RJ Simonsick, EM Brach, JS Ayonayon, H Satterfield, S Harris, TB Garcia, M Kritchevsky, SB AF Thorpe, Roland J., Jr. Simonsick, Eleanor M. Brach, Jennifer S. Ayonayon, Hilsa Satterfield, Suzanne Harris, Tamara B. Garcia, Melissa Kritchevsky, Stephen B. CA Hlth Aging Body Composition Study TI Dog ownership, walking behavior, and maintained mobility in late life SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat DE dog ownership; mobility; physical activity; dog walking; older adults ID TIME PHYSICAL-ACTIVITY; OLDER-ADULTS; COMPANION ANIMALS; PET OWNERSHIP; RISK-FACTORS; ELDERLY-PEOPLE; HEALTH-STATUS; EPIDEMIOLOGY; EXERCISE; POPULATION AB OBJECTIVES: To examine dog walking among dog owners and the relationship between walking behavior of dog owners and non-dog owners and maintained gait speed over 3 years. DESIGN: Cross-sectional and longitudinal analyses of a prospective cohort study. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand five hundred thirty-three community-dwelling adults aged 71 to 82 at 36 months of the Health, Aging and Body Composition Study. MEASUREMENTS: Dog ownership, reported walking behavior, change in walking behavior, and usual and rapid gait speed over 3 years. RESULTS: Of 394 dog owners, only 36% walked their dogs at least three times per week. Cross-sectionally, dog walkers were more likely to achieve 150 minutes of walking per week and had faster usual and rapid walking speeds (1.20 vs 1.14 m/s and 1.62 vs 1.52 m/s, respectively; P <.01 for both) than non-dog owners who did not walk at least three times per week and similar speeds as non-dog owners who walked at least 150 minutes per week (P >.50). Three years later, subjects who had been dog walkers at baseline were approximately twice as likely as any other group to achieve recommended walking levels, independent of covariates. Dog walkers experienced similar declines in usual and rapid walking speed as non-dog owners who walked at least three times per week but maintained their initial mobility advantage. CONCLUSION: Although dog ownership appears to facilitate walking behavior, only a minority of older dog owners walk their dogs. The mobility advantage of dog ownership was seen only in dog walkers and was similar to that associated with any walking. Given suboptimal walking activity in older adults, examining the degree to which dog ownership promotes walking activity in persons who do little walking on their own appears worth pursuing. C1 John Hopkins Bayview Care Ctr, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. RP Thorpe, RJ (reprint author), John Hopkins Bayview Care Ctr, Div Geriatr Med & Gerontol, Dept Med, 5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM rthorpe3@jhmi.edu OI Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, F31-AG-020507, N01-AG-6-2103, N01-AG-6-2106, T32-AG-000120] NR 30 TC 56 Z9 57 U1 1 U2 22 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2006 VL 54 IS 9 BP 1419 EP 1424 DI 10.1111/j.1532-5415.2006.00856.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 081LN UT WOS:000240319200017 PM 16970652 ER PT J AU Chaves, PHM Carlson, MC Ferrucci, L Guralnik, JM Semba, R Fried, LP AF Chaves, Paulo H. M. Carlson, Michelle C. Ferrucci, Luigi Guralnik, Jack M. Semba, Richard Fried, Linda P. TI Association between mild anemia and executive function impairment in community-dwelling older women: The Women's Health and Aging Study II SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Gerontological-Society-of-America CY NOV, 2005 CL Orlando, FL SP Gerontol Soc Amer DE anemia; elderly; executive function; Trail Making Test ID COGNITIVE FUNCTION; HEMOGLOBIN CONCENTRATION; CARDIOVASCULAR-DISEASE; MOBILITY DIFFICULTY; RISK; PERFORMANCE; FITNESS; ADULTS AB OBJECTIVES: To evaluate the relationship between mild anemia and executive function in community-dwelling older women. DESIGN: Cross-sectional. SETTING: Community-based. PARTICIPANTS: High-functioning subjects participating in the baseline assessment of the Women's Health and Aging Study (WHAS) II, Baltimore, Maryland, 1994 to 1996. WHAS II eligibility criteria included aged 70 to 80, a Mini-Mental State Examination score of 24 or greater, and absence of advanced disability (difficulty in no more than 1 domain of physical function). Included in this study were 364 subjects with a hemoglobin concentration 10 g/dL or greater and known executive function status. MEASUREMENTS: Trail Making Test (TMT) Parts B and A. Tertiles of time to complete each test were used to define best (bottom), intermediate, and worst (top) performance. Tertiles of the difference TMT-B minus TMT-A were calculated. Anemia defined as hemoglobin concentration less than 12 g/dL. RESULTS: The percentage of subjects in the worst TMT-B, TMT-A, and TMT-B minus TMT-A performance tertile was highest for those with anemia. Prevalent anemia substantially increased the likelihood of performing worst (as opposed to best) on the TMT-B (odds ratio (OR)=5.2, 95% confidence interval (CI)=1.3-20.5), TMT-A (OR=4.8, 95% CI=1.5-15.6), and TMT-B minus TMT-A (OR= 4.2, 95% CI=1.0-17.2), even after controlling for age, education, race, prevalent diseases, and relevant physiological and functional parameters. CONCLUSION: This study provides preliminary evidence in support of the hypothesis that mild anemia might be an independent risk factor for executive function impairment in community-dwelling older adults. Whether such an association is causal or noncausal remains to be determined. C1 Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD 21205 USA. Univ Estado Rio De Janeiro, Open Univ 3rd Age, Rio De Janeiro, Brazil. NIA, Clin Invest Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Chaves, PHM (reprint author), Johns Hopkins Univ, Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. EM pchaves@jhsph.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000052, M01-RR000052]; NIA NIH HHS [P30 AG021334, R01 AG011703, R01 AG11703] NR 31 TC 50 Z9 52 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2006 VL 54 IS 9 BP 1429 EP 1435 DI 10.1111/j.1532-5415.2006.00863.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 081LN UT WOS:000240319200019 PM 16970654 ER PT J AU Asada-Kamiguchi, J Jones, M Greenberg, NL Popovic, ZB Tsujino, H Zetts, AD Qin, JX Garcia, MJ Thomas, JD Shiota, T AF Asada-Kamiguchi, Junko Jones, Michael Greenberg, Neil L. Popovic, Zoran B. Tsujino, Hiroyuki Zetts, Arthur D. Qin, Jian Xin Garcia, Mario J. Thomas, James D. Shiota, Takahiro TI Intraventricular pressure gradients in left ventricular aneurysms determined by color M-mode Doppler method: An animal study SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID ACUTE MYOCARDIAL-ISCHEMIA; DIASTOLIC FUNCTION; ECHOCARDIOGRAPHY; INFARCTION AB Background: Left ventricular aneurysm (LVA) may affect diastolic intraventricular blood flow. Color M-mode (CMM) Doppler flow propagation patterns are abnormal in the presence of apical aneurysms. The aim of this study was to validate the accuracy of CMM echocardiography for assessing the existence and size of LVA and to determine the intraventricular pressure gradient in LVA. Methods. CMM of the transmitral inflow in early diastole was obtained from the apical 4-chamber view in 19 sheep. The presence of the break point where the velocity decreased abruptly in the mitral inflow (point D) was determined and the distance between the apex and point D was measured. The intraventricular pressure difference between the base and the apex was measured by a catheter while it was calculated using CMM with the Euler equation. Results. The presence of the break point D showed 84% sensitivity and 100% specificity for determining the existence of an LVA. Distance between the apex and point D correlated well with scar size. Catheter- and CMM-derived intraventricular pressure difference correlated and agreed well (y = 1.0 X -0.2, r = 0.94). Conclusions. The point of abrupt decrease in propagation velocity of the CMM recording indicated the presence and size of LVA. Intraventricular pressure gradients were determined noninvasively by CMM echocardiography with reasonable accuracy. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. NHLBI, Bethesda, MD 20892 USA. RP Shiota, T (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Desk F15,9500 Euclid Ave, Cleveland, OH 44195 USA. EM shiotat@ccf.org NR 10 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD SEP PY 2006 VL 19 IS 9 BP 1112 EP 1118 DI 10.1016/j.echo.2006.04.015 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 085DS UT WOS:000240584100005 PM 16950465 ER PT J AU Price, PM Yu, F Kaldis, P Aleem, E Nowak, G Safirstein, RL Megyesi, J AF Price, Peter M. Yu, Fang Kaldis, Philipp Aleem, Eiman Nowak, Grazyna Safirstein, Robert L. Megyesi, Judit TI Dependence of cisplatin-induced cell death in vitro and in vivo on cyclin-dependent kinase 2 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; KINASE INHIBITORS; PROTEIN-KINASES; CDK INHIBITORS; TUBULE CELLS; APOPTOSIS; ACTIVATION; CYCLE; IDENTIFICATION; EXPRESSION AB Cisplatin is one of the most effective chemotherapeutics, but its usefulness is limited by its toxicity to normal tissues, including cells of the kidney proximal tubule. The purpose of these studies was to determine the mechanism of cisplatin cytotoxicity. It was shown in vivo that cisplatin administration induces upregulation of the gene for the p21 cyclin-dependent kinase (cdk) inhibitor in kidney cells. This protein is a positive effector on the fate of cisplatin-exposed renal tubule cells in vivo and in vitro; adenoviral transduction of p21 completely protected proximal tubule cells from cisplatin toxicity. Herein is reported that cdk2 inhibitory drugs protect kidney cells in vivo and in vitro, that transduction of kidney cells in vitro with dominant-negative cdk2 also protected, and that cdk2 knockout cells were resistant to cisplatin. The cdk2 knockout cells regained cisplatin sensitivity after transduction with wild-type cdk2. It is concluded that cisplatin cytotoxicity depends on cdk2 activation and that the mechanism of p21 protection is by directly inhibition of cdk2. This demonstrated the involvement of a protein that previously was associated with cell-cycle progression with pathways of apoptosis. It also was demonstrated that this pathway of cisplatin-induced cell death can be interceded in vivo to prevent nephrotoxicity. C1 Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Physiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Price, PM (reprint author), Univ Arkansas Med Sci, VA Med Ctr, Dept Med, Res Sect, 4300 W 7th St,Room GC 147, Little Rock, AR 72205 USA. EM PricePeterM@uams.edu RI Kaldis, Philipp/G-2714-2010; OI Kaldis, Philipp/0000-0002-7247-7591; Aleem, Eiman/0000-0002-9215-8213 FU NIDDK NIH HHS [P01 DK058324, R01 DK054471, R01 DK55471] NR 53 TC 49 Z9 51 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2006 VL 17 IS 9 BP 2434 EP 2442 DI 10.1681/ASN.2006020162 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 078OP UT WOS:000240113400013 PM 16914540 ER PT J AU Wang, SN de Caestecker, M Kopp, J Mitu, G LaPage, J Hirschberg, R AF Wang, Shinong de Caestecker, Mark Kopp, Jeffrey Mitu, Grace LaPage, Janine Hirschberg, Raimund TI Renal bone morphogenetic protein-7 protects against diabetic nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; PHOSPHOENOLPYRUVATE CARBOXYKINASE; TRANSGENIC MICE; FUSION GENES; CELLS; BMP-7; LOCALIZATION; ACTIVATION; EXPRESSION AB Longstanding diabetes causes renal injury with early dropout of podocytes, albuminuria, glomerular and tubulointerstitial fibrosis, and progressive renal failure. The renal pathology seems to be driven, in part, by TGF-beta and is associated with a loss of renal bone morphogenic protein-7 (BMP-7) expression. Here, the hypothesis that maintenance of renal (especially podocyte) BMP-7 by transgenic expression reduces diabetic renal injury was tested. Diabetic mice that expressed the phosphoenolpyruvate carboxykinase promoter-driven BMP-7 transgene and nondiabetic, transgenic mice as well as diabetic and nondiabetic wild-type controls were studied for up to 1 yr. Transgenic expression of BMP-7 in glomerular podocytes and proximal tubules prevents podocyte dropout and reductions in nephrin levels in diabetic mice. Maintenance of BMP-7 also reduces glomerular fibrosis and interstitial collagen accumulation as well as collagen I and fibronectin expression. Diabetic wild-type mice develop progressive albuminuria, which is substantially reduced in transgenic mice. These effects of the BMP-7 transgene occur without changing renal TGF-beta levels. It is concluded that maintenance of renal BMP-7 during the evolution of diabetic nephropathy reduces diabetic renal injury, especially podocyte dropout. The findings also establish a role for endogenous glomerular BMP-7 as an autocrine regulator of podocyte integrity in vivo. C1 LA Biomed Res Inst, Torrance, CA 90502 USA. Vanderbilt Univ, Div Nephrol, Nashville, TN USA. NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hirschberg, R (reprint author), LA Biomed Res Inst, C-1-A,1124 W Carson St, Torrance, CA 90502 USA. EM rhirschberg@labiomed.org OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS; NIDDK NIH HHS [DK63360] NR 24 TC 108 Z9 129 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2006 VL 17 IS 9 BP 2504 EP 2512 DI 10.1681/ASN.2006030278 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 078OP UT WOS:000240113400020 PM 16899516 ER PT J AU Hemachandra, AH Klebanoff, MA Furth, SL AF Hemachandra, Anusha H. Klebanoff, Mark A. Furth, Susan L. TI Racial disparities in the association between birth weight in the term infant and blood pressure at age 7 years: Results from the Collaborative Perinatal Project SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; ADOLESCENT BODY-SIZE; CARDIOVASCULAR RISK; AFRICAN-AMERICANS; ADULT DISEASE; FETAL ORIGINS; CHILDREN; GROWTH; HYPERTENSION; CHILDHOOD AB BP has been inversely associated with birth weight in studies worldwide, but few studies have included black individuals. The US National Collaborative Perinatal Project followed 58,960 pregnant women and their resultant offspring for 7 yr. In this post hoc analysis, all term white or black children without kidney or heart disease were included (n = 29,710). The effect of birth weight and other risk factors on systolic (SBP) and diastolic BP (DBP) was evaluated at 7 yr. Mean birth weight and body mass index at 7 yr were slightly lower for black compared with white children (birth weight 3.14 +/- 0.48 versus 3.32 +/- 0.46 kg [P < 0.001]; body mass index 15.8 +/- 2.0 versus 16.3 +/- 2.0 [P < 0.001]). Compared with white mothers, black mothers were less likely to smoke (41 versus 52%), were more anemic (23 versus 7%), and were more likely to live in poverty (72 versus 39%). In linear regression, there was significant interaction between race and birth weight in predicting SBP (P = 0.002). In bivariate analysis, birth weight was positively associated with SBP (beta = 0.87) and DBP (beta = 1.14) in black children (P < 0.001) but not associated with either in white children. With maternal poverty, educational level, and anemia during pregnancy added to the model, birth weight remained a significant positive predictor of SBP (beta = 0.89, P < 0.001) in black but not in white children (beta = 0.02, P = 0.17). The association between birth weight and SBP differs between black and white children. The cause of intrauterine growth restriction-associated hypertension seems to be race sensitive; therefore, future studies of racial disparities in the "Barker hypothesis" may help in the understanding of the mechanism of fetal programming of hypertension. C1 Johns Hopkins Univ, Sch Med, Div Neonatol, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Div Pediat Nephrol, Dept Pediat, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hemachandra, AH (reprint author), Johns Hopkins Univ, Sch Med, Div Neonatol, Dept Pediat, 600 N Wolfe St,NH 2-133, Baltimore, MD 21287 USA. EM ahemach@jhmi.edu FU Intramural NIH HHS; NIDDK NIH HHS [U01DK66174] NR 33 TC 16 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2006 VL 17 IS 9 BP 2576 EP 2581 DI 10.1681/ASN.2005090898 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 078OP UT WOS:000240113400028 PM 16870709 ER PT J AU Menon, V Li, LJ Wang, XL Greene, T Balakrishnan, V Madero, M Pereira, AA Beck, GJ Kusek, JW Collins, AJ Levey, AS Sarnak, MJ AF Menon, Vandana Li, Lijun Wang, Xuelei Greene, Tom Balakrishnan, Vaidyanathapuram Madero, Magdalena Pereira, Arema A. Beck, Gerald J. Kusek, John W. Collins, Allan J. Levey, Andrew S. Sarnak, Mark J. TI Adiponectin and mortality in patients with chronic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; TYPE-1 DIABETIC-PATIENTS; ADIPOSE-SPECIFIC PROTEIN; BODY-MASS INDEX; PLASMA ADIPONECTIN; CARDIOVASCULAR EVENTS; INSULIN-RESISTANCE; ARTERY-DISEASE; RENAL-FUNCTION; SERUM ADIPONECTIN AB Adiponectin is presumed to possess antiatherogenic and cardioprotective properties. Limited data exist on the relationship between adiponectin and mortality in the earlier stages of chronic kidney disease. The Modification of Diet in Renal Disease study was a randomized, controlled trial that was conducted between 1989 and 1993. Adiponectin was measured in frozen samples that were obtained at baseline (N = 820). Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of adiponectin with all-cause and cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m(2). Eighty-five percent of participants were white, and 60% were male. Mean +/- SD adiponectin was 12.8 +/- 8.0 mu g/ml. Triglycerides, insulin resistance, glucose, body mass index, GFR, C-reactive protein, and albumin were inversely related and proteinuria and HDL cholesterol were directly related to adiponectin. During the 10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%) from cardiovascular disease. In multivariable adjusted Cox models, a 1-mu g/ml increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95% confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6% (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased risk for cardiovascular mortality. High, rather than low, adiponectin is associated with increased mortality in this cohort of patients with chronic kidney disease stages 3 to 4. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms. C1 Tufts Univ, New England Med Ctr, Div Nephrol, Dept Med, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. RP Menon, V (reprint author), Tufts Univ, New England Med Ctr, Div Nephrol, Dept Med, 750 Washington St,NEMC 391, Boston, MA 02111 USA. EM vmenon@tufts-nemc.org FU NIDDK NIH HHS [K23 DK02904, K23 DK67303, U01 DK35073] NR 41 TC 158 Z9 161 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2006 VL 17 IS 9 BP 2599 EP 2606 DI 10.1681/ASN.2006040331 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 078OP UT WOS:000240113400031 PM 16885405 ER PT J AU Rotnitzky, A Faraggi, D Schisterman, E AF Rotnitzky, Andrea Faraggi, David Schisterman, Enrique TI Doubly robust estimation of the area under the receiver-operating characteristic curve in the presence of verification bias SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE diagnostic test; marker; nonignorable; sensitivity; sensitivity analysis; specificity ID PATTERN-MIXTURE MODELS; 2 DIAGNOSTIC-TESTS; ROC CURVES; SEMIPARAMETRIC REGRESSION; DISEASE VERIFICATION; SCREENING-TESTS; INCOMPLETE DATA; SELECTION BIAS; U-PROCESSES; NONRESPONSE AB The area under the receiver operating characteristic curve (AUC) is a popular summary measure of the efficacy of a medical diagnostic test to discriminate between healthy and diseased subjects. A frequently encountered problem in studies that evaluate a new diagnostic test is that not all patients undergo disease verification because the verification test is expensive, invasive, or both. Furthermore, the decision to send patients to verification often depends on the new test and on other predictors of true disease status. In such cases, usual estimators of the AUC based on verified patients only are biased. In this article we develop estimators of the AUC of markers measured on any scale that adjust for selection to verification. These estimators adjust for measured patient covariates and diagnostic test results and also for an assumed degree of residual selection bias. They can then be used in a sensitivity analysis to examine how the AUC estimates change when different plausible degrees of residual association are assumed. As with other missing-data problems, due to the curse of dimensionality, a model for disease or a model for selection is needed to obtain well-behaved estimators of the AUC when the marker and/or the measured covariates are continuous. We describe a doubly robust estimator that has the attractive feature of being consistent and asymptotically normal if either the disease or the selection model (but not necessarily both) is correct. C1 Di Tella Univ, Buenos Aires, DF, Argentina. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Haifa, IL-31905 Haifa, Israel. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, DHHS, Rockville, MD 20852 USA. RP Rotnitzky, A (reprint author), Di Tella Univ, Buenos Aires, DF, Argentina. EM aromitzky@utdt.edu; Jaraggi@stat.haifa.ac.il; schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X NR 46 TC 19 Z9 19 U1 2 U2 10 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2006 VL 101 IS 475 BP 1276 EP 1288 DI 10.1198/016214505000001339 PG 13 WC Statistics & Probability SC Mathematics GA 079EQ UT WOS:000240158700041 ER PT J AU Sudheendra, D Dromi, S Wood, BJ AF Sudheendra, Deepak Dromi, Sergio Wood, Bradford J. TI Subdermal fluid for skin protection during superficial palliative thermal ablation SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID RADIOFREQUENCY ABLATION; INJURY; COMPLICATIONS; TUMORS C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Sudheendra, D (reprint author), NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C660, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2006 VL 17 IS 9 BP 1545 EP 1547 DI 10.1097/01.RVI.0000232496.73682.00 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 089LW UT WOS:000240883100021 PM 16990478 ER PT J AU Lee, SJ Locklin, JK Wood, BJ AF Lee, S. Justin Locklin, Julia K. Wood, Bradford J. TI Renal vein thrombosis alters treatment times and temperatures in renal tumor Radiofrequency ablation SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter ID CARCINOMA C1 NCI, Dept Diagnost Radiol, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Lee, SJ (reprint author), NCI, Dept Diagnost Radiol, Ctr Clin, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CL999999] NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2006 VL 17 IS 9 BP 1547 EP 1548 DI 10.1097/01.RVI.0000233498.52712.B9 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 089LW UT WOS:000240883100022 PM 16990479 ER PT J AU Jones, KS Fugo, K Petrow-Sadowski, C Huang, Y Bertolette, DC Lisinski, I Cushman, SW Jacobson, S Ruscetti, FW AF Jones, Kathryn S. Fugo, Kazunori Petrow-Sadowski, Cari Huang, Ying Bertolette, Daniel C. Lisinski, Ivonne Cushman, Samuel W. Jacobson, Steven Ruscetti, Francis W. TI Human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 use different receptor complexes to enter T cells SO JOURNAL OF VIROLOGY LA English DT Article ID UBIQUITOUS GLUCOSE-TRANSPORTER; HEPARAN-SULFATE PROTEOGLYCANS; RAT ADIPOSE-CELLS; IMMUNODEFICIENCY-VIRUS; IN-VIVO; CONFERS SUSCEPTIBILITY; ENVELOPE GLYCOPROTEINS; BINDING DOMAIN; TROPISM; LYMPHOCYTES AB Studies using adherent cell lines have shown that glucose transporter-1 (GLUT-1) can function as a receptor for human T-cell leukemia virus type 1 (HTLV). In primary CD4(+) T cells, heparan sulfate proteoglycans (HSPGs) are required for efficient entry of HTLV-1. Here, the roles of HSPGs and GLUT-1 in HTLV-1 and HTLV-2 Env-mediated binding and entry into primary T cells were studied. Examination of the cell surface of activated primary T cells revealed that CD4(+) T cells, the primary target of HTLV-1, expressed significantly higher levels of HSPGs than CD8(+) T cells. Conversely, CD8(+) T cells, the primary target of HTLV-2, expressed GLUT-1 at dramatically higher levels than CD4(+) T cells. Under these conditions, the HTLV-2 surface glycoprotein (SU) binding and viral entry were markedly higher on CD8(+) T cells while HTLV-1 SU binding and viral entry were higher on CD4(+) T cells. Binding studies with HTLV-1/HTLV-2 SU recombinants showed that preferential binding to CD4' T cells expressing high levels of HSPGs mapped to the C-terminal portion of SU. Transfection studies revealed that overexpression of GLUT-1 in CD4(+) T cells increased HTLV-2 entry, while expression of HSPGs on CD8(+) T cells increased entry of HTLV-1. These studies demonstrate that HTLV-1 and HTLV-2 differ in their T-cell entry requirements and suggest that the differences in the in vitro cellular tropism for transformation and in vivo pathobiology of these viruses reflect different interactions between their Env proteins and molecules on CD4' and CD8(+) T cells involved in entry. C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Jones, KS (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Bldg 567,Rm 253, Frederick, MD 21702 USA. EM joneska@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 55 TC 50 Z9 53 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2006 VL 80 IS 17 BP 8291 EP 8302 DI 10.1128/JVI.00389-06 PG 12 WC Virology SC Virology GA 076CL UT WOS:000239934500001 PM 16912281 ER PT J AU Townsley, AC Weisberg, AS Wagenaar, TR Moss, B AF Townsley, Alan C. Weisberg, Andrea S. Wagenaar, Timothy R. Moss, Bernard TI Vaccinia virus entry into cells via a low-pH-dependent endosomal pathway SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR MATURE VIRIONS; SURFACE HEPARAN-SULFATE; MEMBRANE-PROTEIN; ENVELOPE PROTEIN; FUSION; GENE; NEUTRALIZATION; ADSORPTION; POXVIRUSES; COMPLEX AB Previous studies established that vaccinia virus could enter cells by fusion with the plasma membrane at neutral pH. However, low pH triggers fusion of vaccinia virus-infected cells, a hallmark of viruses that enter by the endosomal route. Here, we demonstrate that entry of mature vaccinia virions is accelerated by brief low-pH treatment and severely reduced by inhibitors of endosomal acidification, providing evidence for a predominant low-pH-dependent endosomal pathway. Entry of vaccinia virus cores into the cytoplasm, measured by expression of firefly luciferase, was increased more than 10-fold by exposure to a pH of 4.0 to 5.5. Furthermore, the inhibitors of endosomal acidification bafilomycin A1, concanamycin A, and monensin each lowered virus entry by more than 70%. This reduction was largely overcome by low-pH-induced entry through the plasma membrane, confirming the specificities of the drugs. Entry of vaccinia virus cores with or without brief low-pH treatment was visualized by electron microscopy of thin sections of immunogold-stained cells. Although some virus particles fused with the plasma membrane at neutral pH, 30 times more fusions and a greater number of cytoplasmic cores were seen within minutes after low-pH treatment. Without low-pH exposure, the number of released cores lagged behind the number of virions in vesicles until 30 min post-treatment, when they became approximately equal, perhaps reflecting the time of endosome acidification and virus fusion. C1 NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Lab Viral Dis, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS NR 39 TC 93 Z9 93 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2006 VL 80 IS 18 BP 8899 EP 8908 DI 10.1128/JVI.01053-06 PG 10 WC Virology SC Virology GA 082KF UT WOS:000240384800006 PM 16940502 ER PT J AU Chertova, E Chertov, O Coren, LV Roser, JD Trubey, CM Bess, JW Sowder, RC Barsov, E Hood, BL Fisher, RJ Nagashima, K Conrads, TP Veenstra, TD Lifson, JD Ott, DE AF Chertova, Elena Chertov, Oleg Coren, Lori V. Roser, James D. Trubey, Charles M. Bess, Julian W., Jr. Sowder, Raymond C., II Barsov, Eugene Hood, Brian L. Fisher, Robert J. Nagashima, Kunio Conrads, Thomas P. Veenstra, Timothy D. Lifson, Jeffrey D. Ott, David E. TI Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMISSION ELECTRON-MICROSCOPY; APOLIPOPROTEIN-E; CELLULAR-PROTEINS; ENVELOPE GLYCOPROTEIN; MEMBRANE-VESICLES; MULTIVESICULAR BODIES; TRANSPORT PROTEIN; T-LYMPHOCYTES; HOST ICAM-1; HIV-1 AB Human immunodeficiency virus type I (HIV-1) infects CD4(+) T lymphocytes and monocytes/macrophages, incorporating host proteins in the process of assembly and budding. Analysis of the host cell proteins incorporated into virions can provide insights into viral biology. We characterized proteins in highly purified HIV-1 virions produced from human monocyte-derived macrophages (MDM), within which virus buds predominantly into intracytoplasmic vesicles, in contrast to the plasmalemmal budding of HIV-1 typically seen with infected T cells. Liquid chromatography-linked tandem mass spectrometry of highly purified virions identified many cellular proteins, including 33 previously described proteins in HIV-1 preparations from other cell types. Proteins involved in many different cellular structures and functions were present, including those from the cytoskeleton, adhesion, signaling, intracellular trafficking, chaperone, metabolic, ubiquitin/proteasomal, and immune response systems. We also identified annexins, annexin-binding proteins, Rab proteins, and other proteins involved in membrane organization, vesicular trafficking, and late endosomal function, as well as apolipoprotein E, which participates in cholesterol transport, immunoregulation, and modulation of cell growth and differentiation. Several tetraspanins, markers of the late endosomal compartment, were also identified. MDM-derived HIV contained 26 of 37 proteins previously found in exosomes, consistent with the idea that HIV uses the late endosome/multivesicular body pathway during virion budding from macrophages. C1 NCI, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, AIDS Vaccine Program, Basic Res Program, Frederick, MD 21702 USA. RP Chertova, E (reprint author), NCI, AIDS Vaccine Res Prog, SAIC Frederick Inc, Frederick, MD 21702 USA. EM chertova@ncifcrf.gov RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 79 TC 263 Z9 274 U1 3 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2006 VL 80 IS 18 BP 9039 EP 9052 DI 10.1128/JVI.01013-06 PG 14 WC Virology SC Virology GA 082KF UT WOS:000240384800020 PM 16940516 ER PT J AU Zhang, JC Zhang, GH Guo, R Shapiro, BA Simon, AE AF Zhang, Jiuchun Zhang, Guohua Guo, Rong Shapiro, Bruce A. Simon, Anne E. TI A pseudoknot in a preactive form of a viral RNA is part of a structural switch activating minus-strand synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID TURNIP-CRINKLE-VIRUS; PARALLEL GENETIC ALGORITHM; 3' END; CONFORMATIONAL SWITCH; SATELLITE RNA; REPLICATION REPRESSOR; IN-VITRO; POLYMERASE; SEQUENCE; ELEMENTS AB RNA can adopt different conformations in response to changes in the metabolic status of cells, which can regulate processes such as transcription, translation, and RNA cleavage. We previously proposed that an RNA conformational switch in an untranslated satellite RNA (satC) of Turnip crinkle virus (TCV) regulates initiation of minus-strand synthesis (G. Zhang, J. Zhang, A. T. George, T. Baumstark, and A. E. Simon, RNA 12:147-162, 2006). This model was based on the lack of phylogenetically inferred hairpins or a known pseudoknot in the "preactive" structure assumed by satC transcripts in vitro. We now provide evidence that a second pseudoknot (Psi(2)), whose disruption reduces satC accumulation in vivo and enhances transcription by the TCV RNA-dependent RNA polymerase in vitro, stabilizes the preactive satC structure. Alteration of either AV, partner caused nearly identical structural changes, including single-stranded-specific cleavages in the pseudoknot sequences and strong cleavages in a distal element previously proposed to mediate the conformational switch. These results indicate that the preactive structure identified in vitro has biological relevance in vivo and support a requirement for this alternative structure and a conformational switch in high-level accumulation of satC in vivo. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. RP Simon, AE (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, Microbiol Bldg, College Pk, MD 20742 USA. EM simona@umd.edu RI Zhang, Jiuchun/C-7021-2012; Simon, Anne/B-8713-2014 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM061515, GM 61515-01] NR 43 TC 28 Z9 29 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2006 VL 80 IS 18 BP 9181 EP 9191 DI 10.1128/JVI.00295-06 PG 11 WC Virology SC Virology GA 082KF UT WOS:000240384800033 PM 16940529 ER PT J AU Golbreich, C Zhang, SM Bodenreider, O AF Golbreich, Christine Zhang, Songmao Bodenreider, Olivier TI The foundational model of anatomy in OWL: Experience and perspectives SO JOURNAL OF WEB SEMANTICS LA English DT Article DE anatomy; Foundational Model of Anatomy (FMA); ontology; protege; Web Ontology Language ( OWL); semantic web AB We present the method developed for migrating the Foundational Model of Anatomy ( FMA) from its representation with frames in Prot e eg e to its logical representation in OWL and our experience in reasoning with it. Despite the extensive use of metaclasses in Protege, it proved possible to convert the FMA from Protege into OWL DL, while capturing most of its original features. The conversion relies on a set of translation and enrichment rules implemented with flexible options. Unsurprisingly, reasoning with the FMA in OWL proved to be a real challenge, due to its sheer size and complexity, and raised significant inference problems in terms of time and memory requirements. However, various smaller versions have been successfully handled by Racer. Some inconsistencies were identified and several classes reclassified. The results obtained so far show the advantage of OWL DL over frames and, more generally, the usefulness of DLs reasoners for building and maintaining the large- scale biomedical ontologies of the future Semantic Web. (C) 2006 Elsevier B. V. All rights reserved. C1 Univ Rennes 1, LIM, F-35043 Rennes, France. Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100080, Peoples R China. US Natl Lib Med, Bethesda, MD 20894 USA. RP Golbreich, C (reprint author), Univ Rennes 1, LIM, F-35043 Rennes, France. EM Christine.Golbreich@univ-rennes1.fr; smzhang@math.ac.cn; olivier@nlm.nih.gov NR 16 TC 47 Z9 49 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-8268 J9 J WEB SEMANT JI J. Web Semant. PD SEP PY 2006 VL 4 IS 3 BP 181 EP 195 DI 10.1016/j.websem.2006.05.007 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA 176AB UT WOS:000247054000004 ER PT J AU Cappola, AR Xue, QL Walston, JD Leng, SX Ferrucci, L Guralnik, J Fried, LP AF Cappola, Anne R. Xue, Qian-Li Walston, Jeremy D. Leng, Sean X. Ferrucci, Luigi Guralnik, Jack Fried, Linda P. TI DHEAS levels and mortality in disabled older women: The Women's Health and Aging Study I SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PLASMA DEHYDROEPIANDROSTERONE-SULFATE; RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; RANCHO-BERNARDO; BREAST-CANCER; SEX-HORMONES; MEN; MUSCLE; POPULATION AB Background. Dehydroepiandrosterone sulfate (DHEAS) is an endogenously produced sex steroid that has been hypothesized to have anti-aging effects. Low DHEAS levels are associated with mortality in older men, but the relationship between DHEAS levels and mortality in women is not clearly defined. Methods. The relationship between serum DHEAS level and 5-year mortality was analyzed in a cohort of 539 disabled women aged 65-100 years enrolled in the Women's Health and Aging Study I (WHAS I). Using Cox proportional hazard models, we calculated multivariate-adjusted mortality risks by DHEAS quartiles and by DHEAS continuously, allowing for a nonlinear relationship. We also examined cause-specific mortality. Results. We found a U-shaped relationship between DHEAS level and mortality. After adjusting for multiple covariates, women in the top and bottom DHEAS quartiles had a more than 2-fold higher 5-year mortality than did those in the middle quartiles (hazard ratio, 2.15; 95% confidence interval [CI], 1.17-3.98 for the top quartile and 2.05; 95% CI, 1.27-3.32 for the bottom quartile, each compared to the third quartile). Women with higher DHEAS levels tended to have greater cancer mortality, whereas those with lower DHEAS tended to have greater cardiovascular mortality. Conclusion. Disabled older women with either low or high levels of DHEAS are at greater risk for death than are those with intermediate levels. More research is needed to determine if targeted dehydroepiandrosterone supplementation would provide clinical benefit to disabled older women. C1 Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Johns Hopkins Med Inst, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA. NIA, Clin Res Branch, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. RP Cappola, AR (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Ctr Clin Epidemiol & Biostat, 718 Blockley,423 Guardian Dr, Philadelphia, PA 19104 USA. EM acappola@cceb.med.upenn.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [K23 AG019161, K23 AG19161, N01-AG-1-2112, R01 AG011703, R01-AG11703, R37 AG019905, R37-AG19905] NR 38 TC 26 Z9 27 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2006 VL 61 IS 9 BP 957 EP 962 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 085CP UT WOS:000240581100010 PM 16960027 ER PT J AU Sassen, MC Kim, SW Kwon, TH Knepper, MA T Miller, R Frokiaer, J Nielsen, S AF Sassen, M. C. Kim, S. W. Kwon, T-H Knepper, M. A. T Miller, R. Frokiaer, J. Nielsen, S. TI Dysregulation of renal sodium transporters in gentamicin-treated rats SO KIDNEY INTERNATIONAL LA English DT Article DE renal magnesium wasting; sodium transport; NKCC2; calcium-sensing receptor; nephrotoxicity; concentrating defect ID CALCIUM-SENSING RECEPTOR; DISTAL CONVOLUTED TUBULE; THICK ASCENDING LIMB; STIMULATED MG2+ UPTAKE; K-CL COTRANSPORTER; NA-K-2CL COTRANSPORTER; MAGNESIUM HOMEOSTASIS; PROXIMAL TUBULE; COLLECTING DUCT; KIDNEY AB We aimed to investigate the molecular mechanisms underlying the renal wasting of Na+, K+, Ca2+, and Mg2+ in gentamicin (GM)-treated rats. Male Wistar rats were injected with GM (40 or 80 mg/kg/day for 7 days, respectively; GM-40 or GM-80). The expression of NHE3, Na-K-ATPase, NKCC2, ROMK, NCC, alpha-, beta- and gamma-ENaC, and CaSR was examined in the kidney by immunoblotting and immunohistochemistry. Urinary fractional excretion of Na+, K+, Ca2+, and Mg2+ was increased and urinary concentration was decreased in both GM-40 and GM-80 rats. In cortex and outer stripe of outer medulla (cortex) in GM-80 rats, the expression of NHE3, Na-K-ATPase, and NKCC2 was decreased; NCC expression was unchanged; and CaSR was upregulated compared to controls. In the inner stripe of outer medulla (ISOM) in GM-80 rats, NKCC2 and Na-K-ATPase expression was decreased, whereas CaSR was upregulated, and NHE3 and ROMK expression remained unchanged. In GM-40 rats, NKCC2 expression was decreased in the cortex and ISOM, whereas NHE3, Na-K-ATPase, CaSR, ROMK, and NCC abundance was unchanged in both cortex and ISOM. Immunoperoxidase labeling confirmed decreased expression of NKCC2 in the thick ascending limb (TAL) in both GM-80- and GM-40-treated rats. Immunoblotting and immunohistochemical analysis revealed increased expression of alpha-, beta-, and gamma-ENaC in cortex in GM-80 rats, but not in GM-40 rats. These findings suggest that the decrease in NKCC2 in TAL seen in response to low-dose (40 mg/kg/day) gentamicin treatment may play an essential role for the increased urinary excretion of Mg2+ and Ca2+, and play a significant role for the development of the urinary concentrating defect, and increased urinary excretion of Na+ and K+. At high-dose gentamicin, both proximal and TAL sodium transporter downregulation is likely to contribute to this. C1 Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Univ Aarhus, Inst Anat, Aarhus C, Denmark. Univ Marburg, Marburg, Germany. Chonnam Natl Univ, Med Sch, Dept Internal Med, Kwangju, South Korea. Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu, South Korea. Natl Heart Lung & Blood Inst, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD USA. Case Western Reserve Univ, Louis Stokes VAMC, Nephrol Sect, Cleveland, OH USA. Aarhus Univ Hosp, Inst Clin Med, Aarhus N, Denmark. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Bldg 233-234, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 60 TC 19 Z9 20 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2006 VL 70 IS 6 BP 1026 EP 1037 DI 10.1038/sj.ki.5001654 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 082EU UT WOS:000240370300016 PM 16850027 ER PT J AU Young, O Williams, M AF Young, Owen Williams, Melissa TI Contract support - Melissa Williams discusses her role as senior deputy program manager at the NIH SO LAB ANIMAL LA English DT Editorial Material C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Young, O (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2006 VL 35 IS 8 BP 42 EP 42 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 182QF UT WOS:000247518400010 ER PT J AU Hortin, GL AF Hortin, Glen L. TI Homocysteine: Clinical significance and laboratory measurement SO LABMEDICINE LA English DT Review ID PLASMA TOTAL HOMOCYSTEINE; ENZYMATIC CYCLING ASSAY; DISEASE; RISK; QUANTIFICATION; SERUM AB Increased plasma homcysteine concentrations are associated with increased risk of myocardial infarction, stroke, and venous thrombosis. Potential benefits of homcysteine lowering therapy are stimulating clinical interest in measuring homocysteine. Many methods are now available including some new options. However, homocysteine testing and interpretation present challenges to clinical laboratories. Future demand for homocysteine testing likely will depend on the outcome of ongoing trials of homocysteine-lowering therapy. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD SEP PY 2006 VL 37 IS 9 BP 551 EP 553 DI 10.1309/93G5JG1BF44N65BQ PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 076QN UT WOS:000239972900021 ER PT J AU Buffalo, EA Bellgowan, PSF Martin, A AF Buffalo, Elizabeth A. Bellgowan, Patrick S. F. Martin, Alex TI Distinct roles for medial temporal lobe structures in memory for objects and their locations SO LEARNING & MEMORY LA English DT Article ID EVENT-RELATED FMRI; RECOGNITION MEMORY; PERIRHINAL CORTEX; PARAHIPPOCAMPAL CORTICES; ENTORHINAL CORTEX; BRAIN ACTIVITY; LESIONS; ASSOCIATIONS; HIPPOCAMPAL; REGION AB The ability to learn and retain novel information depends on a system of structures in the medial temporal lobe (MTL) including the hippocampus and the surrounding entorhinal, perirhinal, and parahippocampal cortices. Damage to these structures produces profound memory deficits; however, the unique contribution to memory of each of these structures remains unclear. Here we have used functional magnetic resonance imaging (fMRI) to determine whether the perirhinal and parahippocampal cortices show differential memory-related activity. Based on the distinct patterns of cortical input to these two areas, we reasoned that these structures might show differential activity for spatial and object recognition memory. In each of 11 subjects, we found that the perirhinal cortex was active during both spatial and object memory encoding, while the anterior parahippocampal cortex was active only during spatial encoding. These data support the idea that MTL structures make distinct contributions to recognition memory performance. C1 Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30329 USA. Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Buffalo, EA (reprint author), Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30329 USA. EM elizabeth.buffalo@emory.edu RI martin, alex/B-6176-2009 NR 32 TC 73 Z9 74 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD SEP-OCT PY 2006 VL 13 IS 5 BP 638 EP 643 DI 10.1101/lm.251906 PG 6 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 090FV UT WOS:000240937000023 PM 16980544 ER PT J AU Sconocchia, G del Principe, D Barrett, AJ AF Sconocchia, G. del Principe, D. Barrett, A. J. TI Non-classical antileukemia activity of early recovering NK cells after induction chemotherapy and HLA-identical stem cell transplantation in myeloid leukemias SO LEUKEMIA LA English DT Letter ID CHRONIC MYELOGENOUS LEUKEMIA; NATURAL-KILLER-CELLS; MONOCYTE; BLASTS C1 CNR, Inst Organ Transplantat & Immunocitol, Rome, Italy. Univ Roma Tor Vergata, Sch Med, Dept Pediat, I-00173 Rome, Italy. NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Sconocchia, G (reprint author), CNR, Inst Organ Transplantat & Immunocitol, Rome, Italy. EM giuseppe.sconocchia@itoi.cnr.it NR 12 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2006 VL 20 IS 9 BP 1632 EP 1633 DI 10.1038/sj.leu.2404300 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 077GB UT WOS:000240015800029 PM 16810198 ER PT J AU Dunleavy, K Wilson, WH AF Dunleavy, Kieron Wilson, Wyndham H. TI Primary intraocular lymphoma: Current and future perspectives SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID NERVOUS-SYSTEM LYMPHOMA; B-CELL LYMPHOMA; RADIATION-THERAPY; METHOTREXATE; INVOLVEMENT; MANAGEMENT; DIAGNOSIS; SURVIVAL; DISEASE C1 NCI, Canc Res Ctr, Bethesda, MD USA. RP Wilson, WH (reprint author), NCI, Canc Res Ctr, Bldg 10,Room 4N115,9000 Rockville Pike, Bethesda, MD USA. EM wilsonw@mail.nih.gov NR 15 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2006 VL 47 IS 9 BP 1726 EP 1727 DI 10.1080/10428190600674339 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 099MX UT WOS:000241600200003 PM 17064977 ER PT J AU Neri, M Cesario, A Granone, P Dominioni, L Puntoni, R D'Angelillo, RM Russo, P AF Neri, Monica Cesario, Alfredo Granone, Pierluigi Dominioni, Lorenzo Puntoni, Riccardo D'Angelillo, Rolando Maria Russo, Patrizia TI Prognostic role of K-Ras mutations in non-small cell lung cancer: Still an issue for open debate SO LUNG CANCER LA English DT Letter DE lung cancer; K-Ras ID PLASMA DNA; CHEMOTHERAPY; EXPRESSION; SURVIVAL AB We herein comment a recently published experience on circulating K-ras DNA in lung cancer patients. (C) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Sacred Heart, Div Gen Thorac Surg, Dept Surg Sci, I-00168 Rome, Italy. Natl Canc Inst, Translat Res Lung Canc Unit B, Genoa, Italy. IRCCS San Raffaele, Clin Resp & Pathol Translat Lab, Rome, Italy. Insubria Univ, Dept Thorac Surg, Varese, Italy. Dept Radiotherapy, Rome, Italy. RP Cesario, A (reprint author), Univ Sacred Heart, Div Gen Thorac Surg, Dept Surg Sci, Largo A Gemelli 8, I-00168 Rome, Italy. EM alfcesario@rm.unicatt.it RI CESARIO, Alfredo/O-4215-2015; Neri, Monica/J-6308-2012; OI CESARIO, Alfredo/0000-0003-4687-0709; Neri, Monica/0000-0003-4796-3675; D'Angelillo, Rolando M./0000-0003-3636-6429 NR 10 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD SEP PY 2006 VL 53 IS 3 BP 393 EP 395 DI 10.1016/j.lungcan.2006.06.009 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 082YG UT WOS:000240422500019 PM 16887233 ER PT J AU Nezafat, R Thompson, RB Derbyshire, JA McVeigh, ER AF Nezafat, Reza Thompson, Richard B. Derbyshire, J. Andrew McVeigh, Elliot R. TI Partial field-of-view spiral phase-contrast imaging using complex difference processing SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; flow; rapid imaging; complex difference; spiral ID MAGNETIC-RESONANCE; MR ANGIOGRAPHY; FLOW; RECONSTRUCTION AB Rapid flow imaging was achieved with a partial field of view (pFOV) spiral motion-encoded technique. The FOV and the acquisition time were reduced by a factor of 2 by undersampling k-space. The pFOV spiral k-space trajectory aliased signals from outside a circular ring whose radius was inversely proportional to the distance between adjacent spirals in k-space, In this study the FOV was adjusted so that all of the moving spins were located inside the inner half circle of the full FOV. Complex subtraction of two differentially flow-encoded images was used to remove the spurious phase sources and provide an accurate measurement of flow. The complex subtraction process also serves to eliminate aliasing artifacts that are generated by static tissue from outside the reduced FOV. Experiments in a flow phantom and volunteers showed that the flow estimates obtained by pFOV spiral motion encoding are in good agreement with the estimates reconstructed using complex difference processing. C1 Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. Univ Alberta, Dept Biomed Engn, Edmonton, AB, Canada. RP Nezafat, R (reprint author), 10 Ctr Dr MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM nezafatr@nih.gov RI Thompson, Richard/E-9821-2011 FU Intramural NIH HHS [Z01 HL004608-08] NR 20 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2006 VL 56 IS 3 BP 676 EP 680 DI 10.1002/mrm.20975 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 080KD UT WOS:000240245600026 PM 16804920 ER PT J AU Brozova, E Simeckova, K Kostrouch, Z Rall, JE Kostrouchova, M AF Brozova, Eva Simeckova, Katerina Kostrouch, Zdenek Rall, Joseph Edward Kostrouchova, Marta TI NHR-40, a Caenorhabditis elegans supplementary nuclear receptor, regulates embryonic and early larval development SO MECHANISMS OF DEVELOPMENT LA English DT Article DE nuclear hormone receptors; Caenorhabditis elegans; transcription; development ID CONSTITUTIVE ANDROSTANE RECEPTOR; RETINOID-X-RECEPTOR; C-ELEGANS; HORMONE-RECEPTOR; GENE-EXPRESSION; LIGAND-BINDING; MESSENGER-RNA; HOMOLOG HLH-1; MUSCLE; NEMATODES AB Nuclear hormone receptors (NHRs) are important regulators of development and metabolism in animal species. They are characterized by the ability to regulate gene expression in response to the binding of small hydrophobic molecules, hormones, metabolites, and xenobiotics. The Caenorhabditis elegans genome contains 284 sequences that share homology to vertebrate and insect NHRs, a surprisingly large number compared with other species. The majority of C elegans NHRs are nematode-specific and are referred to as supplementary nuclear receptors (supnrs) that are thought to have originated by duplications of an ancient homolog of vertebrate HNF4. Here, we report on the function of NHR-40, a member of a subgroup of 18 Caenorhabditis elegans supnrs that share DNA-binding domain sequence CNGCKT. NHR-40 is expressed from at least two promoters, generates at least three transcripts, and is detectable in pharyngeal, body wall, and sex muscles as well as in a subset of neurons. The downregulation of nhr-40 by RNAi, or a mutant with an intronic region deletion, results in late embryonic and early larval arrest with defects in elongation and morphogenesis. The nhr-40 loss of function phenotype includes irregular development of body wall muscle cells and impaired movement and coordination resembling neuromuscular affection. NHR-40 joins the list of C elegans NHRs that regulate development and suggests that members of extensive nematode supnr family have acquired varied and novel functions during evolution. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Biol & Genet, CZ-12801 Prague 2, Czech Republic. Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Pathol, CZ-12801 Prague 2, Czech Republic. NIDDK, NIH, Bethesda, MD USA. RP Kostrouchova, M (reprint author), Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Biol & Genet, Ke Karlovu, CZ-12801 Prague 2, Czech Republic. EM marta.kostrouchova@lfl.cuni.cz FU Intramural NIH HHS NR 61 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 EI 1872-6356 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 2006 VL 123 IS 9 BP 689 EP 701 DI 10.1016/j.mod.2006.06.006 PG 13 WC Developmental Biology SC Developmental Biology GA 098HR UT WOS:000241512100004 PM 16920335 ER PT J AU Kantarcioglu, AS Yucel, A Nagao, K Sato, T Inci, E Ogreden, S Kaytaz, A Alan, S Bozdag, Z Edali, N Sar, M Kepil, N Oz, B Altas, K AF Kantarcioglu, A. Serda Yucel, Ayhan Nagao, Keisuke Sato, Tomotaka Inci, Ender Ogreden, Sahin Kaytaz, Asim Alan, Saadet Bozdag, Zehra Edali, Naci Sar, Mehmet Kepil, Nuray Oz, Buge Altas, Kemal TI A Rhizopus oryzae strain isolated from resected bone and soft tissue specimens from a sinonasal and palatal mucormycosis case. Report of a case and in vitro experiments of yeastlike cell development SO MEDICAL MYCOLOGY LA English DT Article DE Rhizopus oryzae (Rhizopus arrhizus); yeast-like cells of Rhizopus oryzae; Rhizopus oryzae sinonasal infection; sinonasal mucormycosis ID COKEROMYCES-RECURVATUS; MUCOR; MORPHOGENESIS; DIMORPHISM AB We report a histologically and mycologically proven sinonasal mucormycosis case causing palatal necrosis in a nondiabetic patient with renal failure. Mycological examination of Giemsa stained imprinted tissue preparations revealed abundant yeast-like cells besides the typical mucoraceous hyphae. The fungus was isolated from surgical specimens and identified as Rhizopus oryzae by phenotypic and genotypic tests. Laboratory studies were performed to investigate the association of the yeast-like cells observed in tissue specimens and the fungus recovered in culture. In vitro induced yeast-like cell development of the case isolate was found under certain growth conditions and documented by photomicrographs. C1 Univ Istanbul, Dept Microbiol & Clin Microbiol, Cerrahpasa Med Fac, TR-34303 Cerrahpasa, Turkey. NIH, Dermatol Branch, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan. Istanbul Univ, Dept Otorhinolaryngol, Cerrahpasa Med Fac, Istanbul, Turkey. Inonu Univ, Div Pathol Lab, Turgut Ozal Med Ctr, Malatya, Turkey. Istanbul Univ, Dept Pathol, Cerrahpasa Med Fac, Istanbul, Turkey. RP Kantarcioglu, AS (reprint author), Univ Istanbul, Dept Microbiol & Clin Microbiol, Cerrahpasa Med Fac, TR-34303 Cerrahpasa, Turkey. EM s.kantarcioglu@superonline.com RI Nagao, Keisuke/J-5116-2013 OI Nagao, Keisuke/0000-0002-7005-3138 NR 29 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD SEP PY 2006 VL 44 IS 6 BP 515 EP 521 DI 10.1080/13693780600764973 PG 7 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 083YG UT WOS:000240494600004 PM 16966168 ER PT J AU Bennett, JE AF Bennett, John E. TI The debate: A case for randomized controls in invasive aspergillosis SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT 2nd Advances against Aspergillosis Conference CY FEB 22-25, 2006 CL Athens, GREECE DE aspergillosis; trials; antifungal ID LIPOSOMAL AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; FUNGAL-INFECTIONS; THERAPY; VORICONAZOLE; TRIAL AB Randomized trials in invasive aspergillosis have evolved over the past decade. Definitions of disease now include specifics of the underlying disease and how this affects interpretation of certain tests, including high resolution computed tomography and smears or cultures of sputum and bronchoalveolar lavage. Study hypotheses have changed from underpowered superiority trials to adequately powered noninferioirty trials. Consensus building between Europe and North America has allowed trials to be conducted with the same protocol in both regions, thereby increasing study enrollment. In aggregate, the following outcomes can be drawn from randomized trials: (i) Liposomal amphotericin B is possibly superior to conventional amphotericin B at 14 days and less toxic. Whether the dose of liposomal amphotericin is 1 or 4 mg/kg daily is not as important as other factors in determining outcome of possible aspergillosis; (ii) amphotericin B colloidal dispersion is less nephrotoxic but has more acute infusion-related reactions than conventional amphotericin B; (iii) starting treatment with voriconazole is superior to starting with conventional amphotericin B. In an era of increasing cost containment, it will be the randomized trials that provide the clinician with the information needed to avoid inappropriate use of expensive drugs and drug combinations. C1 NIAID, Clin Mycol Sect, LCID, Clin Ctr,Lab Clin Invest,NIH, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, LCID, Clin Ctr,Lab Clin Invest,NIH, Room 11C304, Bethesda, MD 20892 USA. EM jbennett@niaid.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD SEP PY 2006 VL 44 SU 1 BP S305 EP S308 DI 10.1080/13693780600835708 PG 4 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 113MG UT WOS:000242601400047 PM 17050456 ER PT J AU Stein, DJ Arya, M Pietrini, P Rapoport, JL Swedo, SE AF Stein, Dan J. Arya, Monisha Pietrini, Pietro Rapoport, Judith L. Swedo, Susan E. TI Neurocircuitry of disgust and anxiety in obsessive-compulsive disorder: A positron emission tomography study SO METABOLIC BRAIN DISEASE LA English DT Article; Proceedings Paper CT Psychiatric and Neurosciences Congress CY APR, 2005 CL Cape Town, SOUTH AFRICA ID ANTICIPATORY ANXIETY; FACIAL EXPRESSIONS; BASIC EMOTIONS; TRAIT ANXIETY; NEURAL BASIS; FEAR; RESPONSES; BRAIN; AMYGDALA; FMRI AB Background: Disgust and fear are basic emotions that have different elicitors and expressions, and that appear to be mediated by different neurocircuits. Although obsessive-compulsive disorder (OCD) is classified as an anxiety disorder, disgust may be involved in its pathogenesis. Functional magnetic resonance imaging (fMRI) studies of disgust-inducing visual stimuli in OCD have suggested disorder specific alterations in brain activation during these tasks. Methods: Subjects with OCD and healthy controls (HQ underwent positron emission tomography (PET) brain scanning after injection of (H2O)-O-15. During PET, subjects either watched slides designed to evoke feelings of disgust (OCD = 5, HC 11), expected the delivery of an electrical shock (OCD = 11, HC = 13), or rested (OCD 11, HC = 14). After the anticipatory anxiety and resting tasks, anxiety ratings, heart rate, and electrodermal measures were obtained. Statistical parametric mapping (SPM) was used to analyze regional cerebral blood flow (rCBF) data. Results: Comparison of OCD subjects with controls on differences in rCBF across the disgust-inducing and resting tasks showed that OCD was characterized by greater rCBF in the left insula. In OCD the disgust-inducing task increased right lateral orbitofrontal cortex rCBF compared to resting, whereas in controls there was no difference in rCBF between these tasks. Anxiety ratings, heart rate, and electrodermal activity increased during anticipatory anxiety in both groups, and comparison of rCBF in OCD subjects with controls in anticipatory anxiety versus resting state also found no significant differences. Conclusions: OCD may be characterized by a disruption in disgust processing, such that there is a decrease in appropriate disgust (such as that evoked by observing disgust in others) and an increase in inappropriate disgust (such as that evoked by contamination stimuli). The insula may play a particularly important role in mediating such putative disruptions. The sample studied here was small, and further work is required to determine whether disgust-induced activation patterns in OCD are more apparent in specific subtypes of this disorder, whether they are specific to OCD, and whether they are normalized by treatment. C1 Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. NIMH, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Stein, DJ (reprint author), Univ Cape Town, Dept Psychiat, ZA-7925 Cape Town, South Africa. EM dan.stein@curie.uct.ac.za RI Stein, Dan/A-1752-2008 OI Stein, Dan/0000-0001-7218-7810 NR 47 TC 29 Z9 30 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD SEP PY 2006 VL 21 IS 2-3 BP 267 EP 277 DI 10.1007/s11011-006-9021-6 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 104IR UT WOS:000241952600018 PM 16850255 ER PT J AU Cabral, E Aurbach, A Killian, JK Barrett, T Cassarino, D AF Cabral, Erik Aurbach, Aaron Killian, J. Keith Barrett, Terry Cassarino, David TI Distinction of benign sebaceous proliferations from sebaceous carcinomas by immunohistochemistry SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Stanford Univ, Med Ctr, Mountain View, CA USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NCI, Bethesda, MD 20892 USA. UT SW Med Ctr, Dallas, TX USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 171 BP 40 EP 40 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400172 ER PT J AU Lugassy, C Kleinman, H Vernon, S Welch, D Barnhill, R AF Lugassy, Claire Kleinman, Hynda Vernon, Stephen Welch, Danny Barnhill, Raymond TI C16 laminin peptide increases melanoma angiotropism and extravascular migration in the shell-less chick CAM assay SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Univ Miami, Miller Sch Med, Miami, FL 33152 USA. NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 185 BP 43 EP 43 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400186 ER PT J AU Harle, LK Elghetany, MT Bryant, BJ Alter, BP AF Harle, Lindsey K. Elghetany, M. Tarek Bryant, Barbara J. Alter, Blanche P. TI Survivin staining of bone marrow biopsies distinguishes inherited from acquired cytopenias: A study of 212 patients SO MODERN PATHOLOGY LA English DT Meeting Abstract CT 26th International Congress of the International-Academy-of-Pathology CY SEP 16-21, 2006 CL Montreal, CANADA SP Int Acad Pathol, United States & Canadian Acad Pathol C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 SU 3 MA 526 BP 115 EP 115 PG 1 WC Pathology SC Pathology GA 077AF UT WOS:000239999400527 ER PT J AU Fountaine, TJ Wincovitch, SM Geho, DH Garfield, SH Pittaluga, S AF Fountaine, Thomas J. Wincovitch, Stephen M. Geho, David H. Garfield, Susan H. Pittaluga, Stefania TI Multispectral imaging of clinically relevant cellular targets in tonsil and lymphoid tissue using semiconductor quantum dots SO MODERN PATHOLOGY LA English DT Article DE immunofluorescence; quantum dots; immunohistochemistry; multiplexing; multispectral; confocal microscopy ID CENTER B-CELLS; IN-VIVO; PLASMA-CELLS; FLUORESCENCE; PROTEIN; MICROSCOPY; DIFFERENTIATION; NANOCRYSTALS; EXPRESSION; PROBES AB Determination of the expression and spatial distribution of molecular epitopes, or antigens, in patient tissue specimens has substantially improved the pathologist's ability to classify disease processes. Certain disease pathophysiologies are marked by characteristic increased or decreased expression of developmentally controlled antigens, defined as Cluster of Differentiation markers, that currently form the foundation for understanding lymphoid malignancies. While chromogens and organic fluorophores have been utilitized for some time in immunohistochemical analyses, developments in synthetic, inorganic fluorophore semiconductors, namely quantum dots, offer a versatile alternative reporter system. Quantum dots are stable fluorophores, are resistant to photobleaching, and are attributed with wide excitation ranges and narrow emission spectra. To date, routinely processed, formalin-fixed tissues have only been probed with two quantum dot reporters simultaneously. In the present study, streptavidin-conjugated quantum dots with distinct emission spectra were tested for their utility in identifying a variety of differentially expressed antigens (surface, cytoplasmic, and nuclear). Slides were analyzed using confocal laser scanning microscopy, which enabled with a single excitation wavelength (488 nm argon laser) the detection of up to seven signals (streptavidin-conjugated quantum dots 525, 565, 585, 605, 655, 705 and 805 nm) plus the detection of 4'6-DiAmidino-2-Phenyllndole with an infra-red laser tuned to 760 nm for two photon excitation. Each of these signals was specific for the intended morphologic immunohistochemical target. In addition, five of the seven streptavidin-conjugated quantum dots tested (not streptavidin-conjugated quantum dots 585 or 805 nm) were used on the same tissue section and could be analyzed simultaneously on routinely processed formalin-fixed, paraffin-embedded sections. Application of this multiplexing method will enable investigators to explore the clinically relevant multidimensional cellular interactions that underlie diseases, simultaneously. C1 NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt Carcinogenesis, CCR Confocal Microscopy Core Facil, Bethesda, MD USA. George Mason Univ, Ctr Appl Proteonom & Mol Med, Manassas, VA USA. RP Pittaluga, S (reprint author), NCI, Lab Pathol, NIH, Bldg 10,Room 2N109,10 Ctr Dr, Bethesda, MD 20892 USA. EM stefpitt@mail.nih.gov FU Intramural NIH HHS NR 31 TC 90 Z9 100 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 IS 9 BP 1181 EP 1191 DI 10.1038/modpathol.3800628 PG 11 WC Pathology SC Pathology GA 077FZ UT WOS:000240015600005 PM 16778828 ER PT J AU Zlobec, I Steele, R Michel, RP Compton, CC Lugli, A Jass, JR AF Zlobec, Inti Steele, Russell Michel, Rene P. Compton, Carolyn C. Lugli, Alessandro Jass, Jeremy R. TI Scoring of p53, VEGF, Bcl-2 and APAF-1 immunohistochemistry and interobserver reliability in colorectal cancer SO MODERN PATHOLOGY LA English DT Article DE interobserver reliability; rectal cancer; immunohistochemistry; scoring system; p53; VEGF ID ENDOTHELIAL GROWTH-FACTOR; RECTAL TUMOR RESPONSE; PREOPERATIVE RADIOTHERAPY; EXPRESSION; CARCINOMA; BRACHYTHERAPY; VALIDATION; APOPTOSIS; SURVIVAL; MARKER AB Molecular tumor markers are often studied in colorectal cancer using immunohistochemistry to determine their prognostic or predictive value. Protein expression is typically assigned a 'positive' score based on a predetermined cutoff. A semiquantitative scoring method that evaluates the percentage of positive tumor cells (0-100%) may provide a better understanding of the prognostic or predictive significance of these markers. The aim of this study was to assess and compare the interobserver agreement of immunohistochemistry scores using a percentage scoring method and three categorical scoring systems. Immunohistochemistry for p53, Bcl-2, vascular endothelial growth factor (VEGF) and apoptotic protease activating factor-1 (APAF-1) was performed on 87 tumor biopsies from patients with rectal carcinoma and scored independently by four pathologists as the percentage of positive tumor cells. Interobserver agreement was assessed by the intraclass correlation coefficient. The intraclass correlation coefficients for p53 and VEGF (40.6) indicate substantial agreement between observers. The distribution of Bcl-2 and APAF-1 scores in addition to weaker interobserver agreement by percentage scoring suggest that this approach may not be appropriate for these proteins. In conclusion, p53 and VEGF protein expression assessed by immunohistochemistry in colorectal cancer and scored as a percentage of positive tumor cells may be a viable alternative scoring method. C1 McGill Univ, Dept Pathol, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Math & Stat, Montreal, PQ, Canada. McGill Univ, Hlth Ctr, Dept Pathol, Montreal, PQ, Canada. NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD USA. RP Zlobec, I (reprint author), McGill Univ, Dept Pathol, 3775 Univ St,Room B22, Montreal, PQ H3A 2B4, Canada. EM inti.zlobec@mail.mcgill.ca NR 30 TC 51 Z9 52 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2006 VL 19 IS 9 BP 1236 EP 1242 DI 10.1038/modpathol.3800642 PG 7 WC Pathology SC Pathology GA 077FZ UT WOS:000240015600011 PM 16741523 ER PT J AU Shi, CS Huang, NN Harrison, K Han, SB Kehrl, JH AF Shi, Chong-Shan Huang, Ning-Na Harrison, Kathleen Han, Sang-Bae Kehrl, John H. TI The mitogen-activated protein kinase kinase kinase kinase GCKR positively regulates canonical and noncanonical Wnt signaling in B lymphocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID N-TERMINAL KINASE; BETA-CATENIN; C-JUN; VERTEBRATE GASTRULATION; PLANAR POLARITY; CONVERGENT EXTENSION; TUMOR-SUPPRESSOR; XENOPUS EMBRYOS; AXIS FORMATION; I-EPSILON AB Wnt ligands bind receptors of the Frizzled (Fz) family to control cell fate, proliferation, and polarity. Canonical Wnt/Fz signaling stabilizes beta-catenin by inactivating GSK3 beta, leading to the translocation of P-catenin to the nucleus and the activation of Wnt target genes. Noncanonical Wnt/Fz signaling activates RhoA and Rac, and the latter triggers the activation of c-Jun N-terntinal kinase (JNK). Here, we show that exposure of B-lymphocytes to Wnt3a-conditioned media activates JNK and raises cytosolic beta-catenin levels. Both the Rac guanine nucleotide exchange factor Asef and the mitogen- activated protein kinase kinase kinase kinase germinal center kinase-related enzyme (GCKR) are required for Wnt-mediated JNK activation in B cells. In addition, we show that GCKR positively affects the R-catenin pathway in B cells. Reduction of GCKR expression inhibits Wnt3a-induced phosphorylation of GSK3 beta at serine 9 and decreases the accumulation of cytosolic beta-catenin. Furthermore, Wnt signaling induces an interaction between GCKR and GSK3 beta. Our findings demonstrate that GCKR facilitates both canonical and noncanonical Wnt signaling in B lymphocytes. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 54 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 17 BP 6511 EP 6521 DI 10.1128/MCB.00209-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074YP UT WOS:000239848800017 PM 16914735 ER PT J AU Chung, HJ Liu, JH Dundr, M Nie, ZQ Sanford, S Levens, D AF Chung, Hye-Jung Liu, Juhong Dundr, Miroslav Nie, Zuqin Sanford, Suzanne Levens, David TI FBPs are calibrated molecular tools to adjust gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FAR UPSTREAM ELEMENT; PROTEIN-PROTEIN INTERACTIONS; TRANSFER-RNA SYNTHETASES; C-MYC TRANSCRIPTION; SINGLE-STRANDED-DNA; MESSENGER-RNA; BINDING-PROTEIN; IN-VIVO; REGULATORY PROTEIN; KH DOMAINS AB The three far-upstream element (FUSE) binding protein (FBP) family members have been ascribed different functions in gene regulation. They were therefore examined with various biochemical, molecular biological, and cell biological tests to evaluate whether their sequence differences reflect functional customization or neutral changes at unselected residues. Each FBP displayed a characteristic profile of intrinsic transcription activation and repression, binding with protein partners, and subeellular trafficking. Although some differences, such as weakened FBP3 nuclear localization, were predictable from primary sequence differences, the unexpected failure of FBP3 to bind the FBP-interacting repressor (FIR) was traced to seemingly conservative substitutions within a small patch of an N-terminal alpha-helix. The transactivation strength and the FIR-binding strength of the FBPs were in the opposite order. Despite their distinguishing features and differential activities, the FBP`s traffic to shared subnuclear sites and regulate many common target genes, including c-myc. Though a variety of functions have been attributed to the FBPs, based upon their panel of shared and unique features, we propose that they constitute a molecular regulatory kit that tunes the expression of shared targets through a common mechanism. C1 NCI, Pathol Lab, CCR, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Rosalind Franklin Univ Med & Sci, Dept Cell Biol & Anat, Abbott Pk, IL 60064 USA. RP Levens, D (reprint author), NCI, Pathol Lab, CCR, Bldg 10,Rm 2N106, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU Intramural NIH HHS NR 48 TC 40 Z9 41 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 17 BP 6584 EP 6597 DI 10.1128/MCB.00754-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074YP UT WOS:000239848800023 PM 16914741 ER PT J AU Yonekura, S Ting, CY Neves, G Hung, K Hsu, SN Chiba, A Chess, A Lee, CH AF Yonekura, Shinichi Ting, Chun-Yuan Neves, Guilherme Hung, Kimberly Hsu, Shu-ning Chiba, Akira Chess, Andrew Lee, Chi-Hon TI The variable transmembrane domain of Drosophila N-cadherin regulates adhesive activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-ADHESION; IN-VIVO; LATERAL DIMERIZATION; CLASSIC CADHERIN; DN-CADHERIN; ORGANIZATION; DIVERSITY; RECEPTOR; GENES; CNS AB Drosophila N-cadherin (CadN) is an evolutionarily conserved classic cadherin which has a large, complex extracellular domain and a catenin-binding cytoplasmic domain. The CadN locus contains three modules of alternative exons (7a/b, 13a/b, and 18a/b) and undergoes alternative splicing to generate multiple isoforms. Using quantitative transcript analyses and green fluorescent protein-based cell sorting, we found that during development CadN alternative splicing is regulated in a temporal but not cell-type-specific fashion. In particular, exon 18b is predominantly expressed during early developmental stages, while exon 18a is prevalent at the late developmental and adult stages. All CadN isoforms share the same molecular architecture but have different sequences in their extracellular and transmembrane domains, suggesting functional diversity. In vitro quantitative cell aggregation assays revealed that all CadN isoforms mediate homophilic interactions, but the isoforms encoded by exon 18b have a higher adhesive activity than those by its alternative, 18a. Domain-swapping experiments further revealed that the different sequences in the transmembrane domains of isoforms are responsible for their differential adhesive activities. CadN alternative splicing might provide a novel mechanism to fine-tune its adhesive activity at different developmental stages or to restrict the use of high-affinity 18b-type isoforms at the adult stage. C1 NICHHD, Lab Gene Regulat & Dev, Unit Neuronal Connect, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Illinois, Dept Cell & Struct Biol, Urbana, IL 61801 USA. RP Lee, CH (reprint author), NICHHD, Lab Gene Regulat & Dev, Unit Neuronal Connect, NIH, Bldg 18T,Room 106,MSC 5431, Bethesda, MD 20892 USA. EM leechih@mail.nih.gov RI Neves, Guilherme/G-8957-2011; Lee, Chi-Hon/G-9190-2012; Ting, chun-yuan/F-6448-2013 OI Neves, Guilherme/0000-0001-6463-6997; FU Intramural NIH HHS; NICHD NIH HHS [HD008748-03, Z01 HD008748] NR 48 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 17 BP 6598 EP 6608 DI 10.1128/MCB.00241-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074YP UT WOS:000239848800024 PM 16914742 ER PT J AU Watford, WT Li, D Agnello, D Durant, L Yamaoka, K Yao, ZJ Ahn, HJ Cheng, TP Hofmann, SR Cogliati, T Chen, A Hissong, BD Husa, MR Schwartzberg, P O'Shea, JJ Gadina, M AF Watford, Wendy T. Li, Denise Agnello, Davide Durant, Lydia Yamaoka, Kunihiro Yao, Zheng Ju Ahn, Hyun-Jong Cheng, Tammy P. Hofmann, Sigrun R. Cogliati, Tiziana Chen, Amy Hissong, Bruce D. Husa, Matthew R. Schwartzberg, Pamela O'Shea, John J. Gadina, Massimo TI Cytohesin binder and regulator (Cybr) is not essential for T- and dendritic-cell activation and differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTORS; PROTEIN; INTERACTS; ADHESION; RECEPTOR; TAMALIN; FAMILY; DOMAIN; JAK3 AB Cybr (also known as Cytip, CASP, and PSCDBP) is an interleukin-12-induced gene expressed exclusively in hematopoietic cells and tissues that associates with Arf guanine nucleotide exchange factors known as cytohesins. Cybr levels are dynamically regulated during T-cell development in the thymus and upon activation of peripheral T cells. In addition, Cybr is induced in activated dendritic cells and has been reported to regulate dendritic cell (DC)-T-cell adhesion. Here we report the generation and characterization of Cybr-deficient mice. Despite the selective expression in hematopoietic cells, there was no intrinsic defect in T- or B-cell development or function in Cybr-deficient mice. The adoptive transfer of Cybr-deficient DCs showed that they migrated efficiently and stimulated proliferation and cytokine production by T cells in vivo. However, competitive stein cell repopulation experiments showed a defect in the abilities of Cybr-deficient T cells to develop in the presence of wild-type precursors. These data suggest that Cybr is not absolutely required for hematopoietic cell development or function, but stem cells lacking Cybr are at a developmental disadvantage compared to wild-type cells. Collectively, these data demonstrate that despite its selective expression in hematopoietic cells, the role of Cybr is limited or largely redundant. Previous in vitro studies using overexpression or short interfering RNA inhibition of the levels of Cybr protein appear to have overestimated its immunological role. C1 NIAMS, MIIB, LCBS, NIH, Bethesda, MD 20892 USA. NCI, Dept Genet, Bethesda, MD 20892 USA. HNGRI, NIH, Bethesda, MD 20892 USA. RP Watford, WT (reprint author), NIAMS, MIIB, LCBS, NIH, Bldg 10,Room 9N256,MSC-1820,10 Ctr Dr, Bethesda, MD 20892 USA. EM watfordw@mail.nih.gov RI Husa, Matthew/G-4850-2012 FU Intramural NIH HHS NR 20 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 17 BP 6623 EP 6632 DI 10.1128/MCB.02460-05 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 074YP UT WOS:000239848800026 PM 16914744 ER PT J AU Zhang, Y Liao, MJ Dufau, ML AF Zhang, Ying Liao, Mingjuan Dufau, Maria L. TI Phosphatidylinositol 3-kinase/protein kinase Q-induced phosphorylation of Sp1 and p107 repressor release have a critical role in histone deacetylase inhibitor-mediated depression of transcription of the luteinizing hormone receptor gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-ZETA; PROTEIN-KINASES; ERYTHROID-DIFFERENTIATION; REGULATE TRANSCRIPTION; LEUKEMIA-CELLS; RAT ADIPOCYTES; PROMOTER; ACTIVATION; EXPRESSION; BUTYRATE AB We have demonstrated that silencing of luteinizing hormone receptor (LHR) gene transcription is mediated via a proximal Sp1 site at its promoter. Trichostatin A (TSA) induced histone acetylation and gene activation in JAR cells that prevailed in the absence of changes in Sp1/Sp3 expression, their binding activity, disassociation of the histone deacetylase/mSin3A complex from the Sp1 site, or demethylation of the promoter. This indicated a different mechanism involved in TSA-induced derepression. The present studies have revealed that phosphatidylinositol 3-kinase/protein kinase C zeta (PI3K/PKC zeta)-mediated Sp1 phosphorylation accounts for Sp1 site-dependent LHR gene activation. TSA caused marked phosphorylation of Sp1 at serine 641 in JAR and MCF-7 cells. Blockade of PI3K or PKC zeta activity by specific inhibitors, kinase-deficient mutants, or small interfering RNA abolished the effect of TSA on the LHR gene and Sp1 phosphorylation. PKC zeta was shown to associate with Sp1, and this association was enhanced by TSA. Sp1 phosphorylation at serine 641 was required for the release of the pRb homologue p107 from the LHR gene promoter, while p107 acted as a repressor of the LHR gene. Inhibition of PKC zeta activity blocked the dissociation of p107 from the LHR gene promoter and markedly reduced Sp1 phosphorylation and transcription. These results have demonstrated that phosphorylation of Sp1 by PI3K/PKC zeta is critical for TSA-activated LHR gene expression. These studies have revealed a novel mechanism of TSA action through derecruitment of a repressor from the LHR gene promoter in a PI3K/PKC zeta-induced Sp1 phosphorylation-dependent manner. C1 NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A-36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov FU Intramural NIH HHS NR 60 TC 43 Z9 44 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 18 BP 6748 EP 6761 DI 10.1128/MCB.00560-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 084BB UT WOS:000240505400002 PM 16943418 ER PT J AU Chao, C Wu, ZQ Mazur, SJ Borges, H Rossi, M Lin, TX Wang, JYJ Anderson, CW Appella, E Xu, Y AF Chao, Connie Wu, Zhiqun Mazur, Sharlyn J. Borges, Helena Rossi, Matteo Lin, Tongxiang Wang, Jean Y. J. Anderson, Carl W. Appella, Ettore Xu, Yang TI Acetylation of mouse p53 at lysine 317 negatively regulates p53 apoptotic activities after DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RADIATION-INDUCED APOPTOSIS; C-TERMINAL DOMAIN; TRANSCRIPTIONAL REPRESSION; TUMOR-SUPPRESSOR; POSTTRANSLATIONAL MODIFICATIONS; BINDING SITES; TARGET GENES; IN-VIVO; ACTIVATION; DEATH AB Posttranslational modifications of p53, including phosphorylation and acetylation, play important roles in regulating p53 stability and activity. Mouse p53 is acetylated at lysine 317 by PCAF and at multiple lysine residues at the extreme carboxyl terminus by CBP/p300 in response to genotoxic and some nongenotoxic stresses. To determine the physiological roles of p53 acetylation at lysine 317, we introduced a Lys317-to-Arg (K317R) missense mutation into the endogenous p53 gene of mice. p53 protein accumulates to normal levels in p53(K317R) mouse embryonic fibroblasts (MEFs) and thymocytes after DNA damage. While p53-dependent gene expression is largely normal in p53(K317R) MEFs after various types of DNA damage, increased p53-dependent apoptosis was observed in p53(K317R) thymocytes, epithelial cells from the small intestine, and cells from the retina after ionizing radiation (IR) as well as in E1A/Ras-expressing MEFs after doxorubicin treatment. Consistent with these findings, p53-dependent expression of several proapoptotic genes was significantly increased in p53(K317R) thymocytes after IR. These findings demonstrate that acetylation at lysine 317 negatively regulates p53 apoptotic activities after DNA damage. C1 Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Xu, Y (reprint author), Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM yangxu@ucsd.edu RI Borges, Helena/E-5044-2013; Lin, Tongxiang/I-4695-2013 OI Borges, Helena/0000-0003-2866-4223; Lin, Tongxiang/0000-0001-7033-6982 FU NCI NIH HHS [R01 CA094254, CA 94254, R01 CA043054] NR 55 TC 66 Z9 68 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 18 BP 6859 EP 6869 DI 10.1128/MCB.00062-06 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 084BB UT WOS:000240505400011 PM 16943427 ER PT J AU Warming, S Rachel, RA Jenkins, NA Copeland, NG AF Warming, Soren Rachel, Rivka A. Jenkins, Nancy A. Copeland, Neal G. TI Zfp423 is required for normal cerebellar development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ZINC-FINGER PROTEIN; B-CELL LYMPHOMAS; RETROVIRAL INTEGRATION; NEURONAL DEVELOPMENT; ESCHERICHIA-COLI; MOUSE CEREBELLUM; GENE; EFFICIENT; EBF; DNA AB Zinc finger protein 423 (also known as Ebf-associated zinc finger protein, Ebfaz) binds to and negatively regulates Ebf1, a basic helix-loop-helix transcription factor required for B-cell lineage commitment and olfactory epithelium development. Zfp423 also binds to Smad1/Smad4 in response to Bmp2 signaling. Zfp423 contains 30 Kruppel-like zinc fingers that are organized into discrete clusters; some zinc fingers are used to bind DNA, while others mediate Zfp423's interaction with other signaling proteins such as Ebf1 and Smad1/Smad4. Previously, we showed that Zfp423 is an oncogene whose upregulation following retroviral integration in murine B cells leads to an arrest in B-cell differentiation and the subsequent development of B-cell lymphomas. To study the biological functions of Zfp423 in vivo, we used recombineering and gene targeting to generate mice that carry conditional as well as null alleles of Zfp423. Homozygous Zfp423 null mice are runted and ataxic, the cerebellum is underdeveloped, and the vermis is severely reduced. In the remaining cerebellar structures, the Purkinje cells are poorly developed and mislocalized. In mice carrying a hypomorphic Zfp423 gene trap allele, lacZ expression in the cerebellum correlates with the Purkinje cell layer, suggesting that these phenotypes are a result of a Purkinje cell-intrinsic defect. C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Ft Detrick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, 1050 Boyles St,Bldg 539,Room 229, Ft Detrick, MD 21702 USA. EM copeland@ncifcrf.gov FU Intramural NIH HHS NR 28 TC 51 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 18 BP 6913 EP 6922 DI 10.1128/MCB.02255-05 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 084BB UT WOS:000240505400016 PM 16943432 ER PT J AU Kim, SS Cao, L Lim, SC Li, CL Wang, RH Xu, XL Bachelier, R Deng, CX AF Kim, Sang Soo Cao, Liu Lim, Sung-Chul Li, Cuiling Wang, Rui-Hong Xu, Xiaoling Bachelier, Richard Deng, Chu-Xia TI Hyperplasia and spontaneous tumor development in the gynecologic system in mice lacking the BRCA1-Delta 11 isoform SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FULL-LENGTH ISOFORM; DNA-DAMAGE REPAIR; BREAST-CANCER; CYCLIN-E; CENTROSOME DUPLICATION; GENETIC INSTABILITY; CELL-CYCLE; BRCA1; EXPRESSION; SUSCEPTIBILITY AB Alternative splicing in the BRCA1 locus generates multiple protein products including BRCA1-Delta 11, which is identical to the BRCA1 full-length isoform (BRCA1-FL) except for the absence of exon 11. Mutation analysis using gene targeting to create null mutations or disrupt BRCA-FL has provided much of our understanding of BRCA1 functions; however, targeted mutation of specific short forms of BRCA1 has not been reported. To understand the physiologic functions of BRCA1-Delta 11, we used a knock-in approach that blocks alternative splicing between exons 10 and 12 to prevent the formation of this form of BRCA1 We showed that homozygous mutant mice (Brca1(FL/FL))were born at a Mendelian ratio without obvious developmental defects. However, the majority of Brca1(FL/FL) female mice showed mammary gland abnormalities and uterine hyperplasia after one year of age with spontaneous tumor formation. Cultured Brca1(FL/FL) cells exhibited abnormal centrosome amplification and reduction of G, population that was accompanied by accumulation of cyclin E and cyclin A. Accumulation of cyclin E was also found in epithelial layers of dilated ducts and hyperproliferative lobular regions in the mammary glands of Brca1(FL/FL) mice. These observations provide evidence that BRCA1 splicing variants are involved in BRCA1 functions in modulating G Delta(1)/S transition, centrosome duplication, and repressing tumor formation. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Chosun Univ, Dept Pathol, Coll Med, Kwangju 501759, South Korea. Natl Canc Ctr, Div Radiol & Nucl Med, Goyang 411769, Gyeonggi, South Korea. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM ChuxiaD@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 44 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2006 VL 26 IS 18 BP 6983 EP 6992 DI 10.1128/MCB.00796-06 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 084BB UT WOS:000240505400022 PM 16943438 ER PT J AU McCroskery, S Chaudhry, A Lin, L Daniels, MP AF McCroskery, Seumas Chaudhry, Amal Lin, Lin Daniels, Mathew P. TI Transmembrane agrin regulates filopodia in rat hippocampal neurons in culture SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; SYNAPSE FORMATION; RECOMBINANT AGRIN; CORTICAL-NEURONS; DEFICIENT MICE; AXONAL GROWTH; IN-VIVO; PROTEIN; EXPRESSION; DYNAMICS AB Filopodia mediate axon guidance, neurite branching and synapse formation, but the membrane molecules that regulate neuronal filopodia in response to extracellular cues are largely unknown. The transmembrane isoform of the proteoglycan agrin, expressed predominantly in the CNS, may regulate neurite outgrowth, synapse formation and excitatory signaling. Here we demonstrate that agrin positively regulates neuronal filopodia. Over-expression of TM-agrin caused the formation of excess filopodia on neurites of hippocampal neurons cultured 1-6 days. Conversely, suppression of agrin expression by siRNA reduced the number of filopodia. Time lapse analysis indicated that endogenous TM-agrin regulates filopodia by increasing their stability and initiation. The N-terminal half of agrin was necessary for induction of filopodia, and over-expression of TM-agrin in a neuronal cell line increased Cdc42 activation, suggesting a role for Cdc42 downstream of agrin. By positively regulating filopodia in developing neurons, TM-agrin may influence the pattern of neurite outgrowth and synapse formation. (c) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Daniels, MP (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Dr,Bldg 50,Rm 3318, Bethesda, MD 20892 USA. EM danielsm2@mail.nih.gov NR 48 TC 38 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD SEP PY 2006 VL 33 IS 1 BP 15 EP 28 DI 10.1016/j.mcn.2006.06.004 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 084AL UT WOS:000240503800002 PM 16860570 ER PT J AU Mood, K Saucier, C Bong, YS Lee, HS Park, M Daar, IO AF Mood, Kathleen Saucier, Caroline Bong, Yong-Sik Lee, Hyun-Shik Park, Morag Daar, Ira O. TI Gab1 is required for cell cycle transition, cell proliferation, and transformation induced by an oncogenic Met receptor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; GRB2 BINDING-SITE; EPITHELIAL MORPHOGENESIS DOWNSTREAM; PHOSPHOLIPASE C-GAMMA; DOCKING PROTEIN GAB1; TYROSINE KINASE; XENOPUS-OOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; PATHWAYS DOWNSTREAM; BRANCHING TUBULOGENESIS AB We have shown previously that either Grb2- or Shc-mediated signaling from the oncogenic Met receptor Tpr-Met is sufficient to trigger cell cycle progression in Xenopus oocytes. However, direct binding of these adaptors to Tpr-Met is dispensable, implying that another Met binding partner mediates these responses. In this study, we show that overexpression of Grb2-associated binder 1 (Gab1) promotes cell cycle progression when Tpr-Met is expressed at suboptimal levels. This response requires that Gab1 possess an intact Met-binding motif, the pleckstrin homology domain, and the binding sites for phosphatidylinositol 3-kinase and tyrosine phosphatase SHP-2, but not the Grb2 and CrkIl/phospholipase C gamma binding sites. Importantly, we establish that Gab1-mediated signals are critical for cell cycle transition promoted by the oncogenic Met and fibroblast growth factor receptors, but not by progesterone, the natural inducer of cell cycle transition in Xenopus oocytes. Moreover, Gab1 is essential for Tpr-Met-mediated morphological transformation and proliferation of fibroblasts. This study provides the first evidence that Gab1 is a key binding partner of the Met receptor for induction of cell cycle progression, proliferation, and oncogenic morphological transformation. This study identifies Gab1 and its associated signaling partners as potential therapeutic targets to impair proliferation or transformation of cancer cells in human malignancies harboring a deregulated Met receptor. C1 Natl Canc Inst, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. McGill Univ, Ctr Hlth, Mol Oncol Grp, Montreal, PQ H3A 1A1, Canada. McGill Univ, Ctr Hlth, Dept Biochem, Montreal, PQ H3A 1A1, Canada. McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Ctr Hlth, Dept Oncol, Montreal, PQ H3A 1A1, Canada. RP Daar, IO (reprint author), Natl Canc Inst, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM daar@ncifcrf.gov RI Lee, Hyun-Shik/G-3555-2011; OI Daar, Ira/0000-0003-2657-526X FU Intramural NIH HHS NR 58 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 2006 VL 17 IS 9 BP 3717 EP 3728 DI 10.1091/mbc.E06-03-0244 PG 12 WC Cell Biology SC Cell Biology GA 078SZ UT WOS:000240125000001 PM 16775003 ER PT J AU Orjalo, AV Arnaoutov, A Shen, ZX Boyarchuk, Y Zeitlin, SG Fontoura, B Briggs, S Dasso, M Forbes, DJ AF Orjalo, Arturo V. Arnaoutov, Alexei Shen, Zhouxin Boyarchuk, Yekaterina Zeitlin, Samantha G. Fontoura, Beatriz Briggs, Steven Dasso, Mary Forbes, Douglass J. TI The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID NUCLEAR-PORE COMPLEX; XENOPUS EGG EXTRACTS; MESSENGER-RNA EXPORT; GTP-BOUND RAN; MITOTIC SPINDLE; IMPORTIN-BETA; IN-VIVO; POLY(A)(+) RNA; FUNCTIONALLY INTERACTS; CHECKPOINT PROTEINS AB The Nup107-160 complex is a critical subunit of the nuclear pore. This complex localizes to kinetochores in mitotic mammalian cells, where its function is unknown. To examine Nup107-160 complex recruitment to kinetochores, we stained human cells with antisera to four complex components. Each antibody stained not only kinetochores but also prometaphase spindle poles and proximal spindle fibers, mirroring the dual prometaphase localization of the spindle checkpoint proteins Mad1, Mad2, Bub3, and Cdc20. Indeed, expanded crescents of the Nup107-160 complex encircled unattached kinetochores, similar to the hyperaccumulation observed of dynamic outer kinetochore checkpoint proteins and motors at unattached kinetochores. In mitotic Xenopus egg extracts, the Nup107-160 complex localized throughout reconstituted spindles. When the Nup107-160 complex was depleted from extracts, the spindle checkpoint remained intact, but spindle assembly was rendered strikingly defective. Microtubule nucleation around sperm centrosomes seemed normal, but the microtubules quickly disassembled, leaving largely unattached sperm chromatin. Notably, Ran-GTP caused normal assembly of microtubule asters in depleted extracts, indicating that this defect was upstream of Ran or independent of it. We conclude that the Nup107-160 complex is dynamic in mitosis and that it promotes spindle assembly in a manner that is distinct from its functions at interphase nuclear pores. C1 Univ Calif San Diego, Sch Med, Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA. NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. RP Forbes, DJ (reprint author), Univ Calif San Diego, Sch Med, Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. EM DForbes@UCSD.edu OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06]; NIGMS NIH HHS [R01 GM033279, R01 GM033279-23, R01 GM-33279] NR 85 TC 91 Z9 97 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 2006 VL 17 IS 9 BP 3806 EP 3818 DI 10.1091/mbc.E05-11-1061 PG 13 WC Cell Biology SC Cell Biology GA 078SZ UT WOS:000240125000008 PM 16807356 ER PT J AU Melillo, G AF Melillo, Giovanni TI Inhibiting hypoxia-inducible factor 1 for cancer therapy SO MOLECULAR CANCER RESEARCH LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; SMALL-MOLECULE INHIBITOR; FACTOR 1-ALPHA; TUMOR-GROWTH; MAMMALIAN TARGET; SOLID TUMORS; EXPRESSION; PATHWAY; ANGIOGENESIS; HIF-1-ALPHA AB Hypoxia has long been recognized as a common feature of solid tumors and a negative prognostic factor for response to treatment and survival of cancer patients. The discovery of hypoxia-inducible factor 1 (HIF-1), a molecular determinant of the response of mammalian cells to hypoxia, has led to the identification of a ''molecular target" of hypoxia suitable for the development of cancer therapeutics. Early controversy about whether or not HIF-1 is a good target for therapy has not discouraged academic groups and pharmaceutical companies from actively engaging in the discovery of small-molecule inhibitors of HIF. However, what. is the best strategy to inhibit HIF and how HIF inhibitors should be developed for treatment of human cancers is still poorly defined. In this review, aspects related to the identification and early development of novel HIF inhibitors are discussed. Identification and validation of pharmacodynamic end points relevant to the HIF-1 pathway is essential for a rational development of HIF inhibitors. Integration of these biomarkers in early clinical trials may provide valuable information to determine the contribution of HIF inhibitors to response to therapy. Finally, HIF inhibitors should be incorporated in combination strategies to effectively target multiple cellular components of the tumor microenvironment and redundant signaling pathways frequently deregulated in human cancer. C1 NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Melillo, G (reprint author), NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Sci Applicat Int Corp, Room 218,Bldg 432, Frederick, MD 21702 USA. EM melillog@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 59 TC 109 Z9 122 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2006 VL 4 IS 9 BP 601 EP 605 DI 10.1158/1541-7786.MCR-06-0235 PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 084UF UT WOS:000240559200001 PM 16940159 ER PT J AU Mimnaugh, EG Xu, WP Vos, M Yuan, XT Neckers, L AF Mimnaugh, Edward G. Xu, Wanping Vos, Michele Yuan, Xitong Neckers, Len TI Endoplasmic reticulum vacuolization and valosin-containing protein relocalization result from simultaneous Hsp90 inhibition by geldanamycin and proteasome inhibition by Velcade SO MOLECULAR CANCER RESEARCH LA English DT Article ID HEAT-SHOCK RESPONSE; AAA-ATPASE; CELL-DEATH; IN-VIVO; MOLECULAR CHAPERONES; ELEVATED EXPRESSION; AGGRESOME FORMATION; MYELOMA CELLS; DNA-DAMAGE; ER STRESS AB Geldanamycin and Velcade, new anticancer drugs with novel mechanisms of action, are currently undergoing extensive clinical trials. Geldanamycin interrupts Hsp90 chaperone activity and causes down-regulation of its many client proteins by the ubiquitin-proteasome pathway; Velcade is a specific proteasome inhibitor. Misfolded Hsp90 clients within the endoplasmic reticulum (ER) lumen are cleared by ER-associated protein degradation, a sequential process requiring valosin-containing protein (VCP)-dependent retrotranslocation followed by ubiquitination and proteasomal proteolysis. Cotreatment of cells with geldanamycin and Velcade prevents destruction of destabilized, ubiquitinated Hsp90 client proteins, causing them to accumulate. Here, we report that misfolded protein accumulation within the ER resulting from geldanamycin and Velcade exposure overwhelms the ability of the VCP-centered machine to maintain the ER secretory pathway, causing the ER to distend into conspicuous vacuoles. Overexpression of dominant-negative VCP or the "small VCP-interacting protein" exactly recapitulated the vacuolated phenotype provoked by the drugs, associating loss of VCP function with ER vacuolization. In cells transfected with a VCP-enhanced yellow fluorescent protein fluorescent construct, geldanamycin plus Velcade treatment redistributed VCP-enhanced yellow fluorescent protein from the cytoplasm and ER into perinuclear aggresomes. In further support of the view that compromise of VCP function is responsible for ER vacuolization, small interfering RNA interference of VCP expression induced ER vacuolization that was markedly increased by Velcade. VCP knockdown by small interfering RNA eventually deconstructed both the ER and Golgi and interdicted protein trafficking through the secretory pathway to the plasma membrane. Thus, simultaneous geldanamycin and Velcade treatment has far-reaching secondary cytotoxic consequences that likely contribute to the cytotoxic activity of this anticancer drug combination. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Rm 1-5940, Bethesda, MD 20892 USA. EM len@helix.nih.gov FU Intramural NIH HHS NR 99 TC 51 Z9 51 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2006 VL 4 IS 9 BP 667 EP 681 DI 10.1158/1541-7786.MCR-06-0019 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 084UF UT WOS:000240559200007 PM 16966435 ER PT J AU Huang, RL Wallqvist, A Covell, DG AF Huang, Ruili Wallqvist, Anders Covell, David G. TI Targeting changes in cancer: assessing pathway stability by comparing pathway gene expression coherence levels in tumor and normal tissues SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID INSTITUTES ANTICANCER SCREEN; SYSTEMS BIOLOGY; DRUG DISCOVERY; LIFE; IDENTIFICATION; INHIBITION; PREDICTION; MECHANISM; DIAGNOSIS; NETWORKS AB The purpose of this study is to examine gene expression changes occurring in cancer from a pathway perspective by analyzing the level of pathway coherence in tumor tissues in comparison with their normal counterparts. Instability in pathway regulation patterns can be considered either as a result of or as a contributing factor to genetic instability and possibly cancer. Our analysis has identified pathways that show a significant change in their coherence level in tumor tissues, some of which are tumor type specific, indicating novel targets for cancer type-specific therapies. Pathways are found to have a general tendency to lose their gene expression coherence in tumor tissues when compared with normal tissues, especially for signaling pathways. The selective growth advantage of cancer cells over normal cells seems to originate from their preserved control over vital pathways to ensure survival and altered signaling, allowing excessive proliferation. We have additionally investigated the tissue-related instability of pathways, providing valuable clues to the cellular processes underlying the tumorigenesis and/or growth of specific cancer types. Pathways that contain known cancer genes (i.e., "cancer pathways") show significantly greater instability and are more likely to become incoherent in tumor tissues. Finally, we have proposed strategies to target instability (i.e., pathways that are prone to changes) by identifying compound groups that show selective activity against pathways with a detectable coherence change in cancer. These results can serve as guidelines for selecting novel agents that have the potential to specifically target a particular pathway that has relevance in cancer. C1 Natl Canc Inst Frederick, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. Natl Canc Inst Frederick, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. RP Covell, DG (reprint author), Natl Canc Inst Frederick, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. EM covell@ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 50 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2006 VL 5 IS 9 BP 2417 EP 2427 DI 10.1158/1535-7163.MCT-06-0239 PG 11 WC Oncology SC Oncology GA 086RX UT WOS:000240691800031 PM 16985076 ER PT J AU Stern, MC Conway, K Li, Y Mistry, K Taylor, JA AF Stern, Mariana C. Conway, Kathleen Li, Yu Mistry, Kusum Taylor, Jack A. TI DNA repair gene polymorphisms and probability of p53 mutation in bladder cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE p53; epidemiology; bladder cancer; polymorphism ID XRCC1 POLYMORPHISMS; 399GLN POLYMORPHISM; LUNG-CANCER; XPD; SMOKING; RISK; ADDUCTS; FREQUENCY; CELLS; EXPOSURE AB We investigated if the presence of single nucleotide polymorphisms (SNPs) in the XRCC1, XRCC3, and XPD genes were associated with the type and frequency of p53 mutations in bladder cancer. Using a hospital-based case-control study we have previously reported risks for the XRCC1 codon 194, XRCC1 codon 399, XRCC3 codon 241, and XPD codon 751 SNPs [1-3]. We have also previously reported mutation data for 149 cases from this study who were screened for mutations in exons 4 through 9 of the p53 gene [4]. Here we investigate possible associations between the DNA repair SNPs mentioned above and the presence of p53 mutations by comparing the frequency of each genotype between p53 mutation positive and negative cases. We also considered different classes of p53 mutations, including any mutation (nonsense, missense or silent), transversions and transitions and estimated odds ratios (ORs) and 95% confidence intervals (Cl) for these associations. Cases with the XRCC1 codon 399 GIn/GIn genotype were positively associated with the presence of p53 transversions (OR= 4.8; 94% Cl=0.8-30). Cases with the XPD codon 751 Gln/Gln genotype were positively associated with the presence of p53 transitions (OR=2.8; 95% Cl=0.8-9.3), in particular G:C-A:T transitions (OR=3.7; 95% Cl=1.1-13). Our data provide some limited support for the hypothesis that mutations in the p53 gene in bladder cancer may differ according to the presence or absence of certain DNA repair gene variants. Published 2006 Wiley-Liss, Inc.(dagger) C1 Natl Inst Environm Hlth Sci, Mol & Genet Epidemiol Grp, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Taylor, JA (reprint author), Natl Inst Environm Hlth Sci, Mol & Genet Epidemiol Grp, Mol Carcinogenesis Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS NR 27 TC 20 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 2006 VL 45 IS 9 BP 715 EP 719 DI 10.1002/mc.20210 PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 081OL UT WOS:000240326800010 PM 16652373 ER PT J AU Shreeram, S Demidov, ON Hee, WK Yamaguchi, H Onishi, N Kek, C Timofeev, ON Dudgeon, C Fornace, AJ Anderson, CW Minami, Y Appella, E Bulavin, DV AF Shreeram, Sathyavageeswaran Demidov, Oleg N. Hee, Weng Kee Yamaguchi, Hiroshi Onishi, Nobuyuki Kek, Calvina Timofeev, Oleg N. Dudgeon, Crissy Fornace, Albert J. Anderson, Carl W. Minami, Yasuhiro Appella, Ettore Bulavin, Dmitry V. TI Wip1 phosphatase modulates ATM-dependent signaling pathways SO MOLECULAR CELL LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CELL-CYCLE CHECKPOINTS; ATAXIA-TELANGIECTASIA; CHROMOSOMAL IMBALANCES; PROTEIN PHOSPHATASE; BREAST-CANCER; UV-RADIATION; PPM1D; ACTIVATION; KINASE AB Deletion of Ppm1d, the gene encoding the Wip1 phosphatase, renders cells resistant to transformation and mice resistant to tumor development. Here, we report that deficiency of Wip1 resulted in activation of the ataxia-telangiectasia mutated (ATM) kinase. In turn, overexpression of Wip1 was sufficient to reduce activation of the ATM-dependent signaling cascade after DNA damage. Wip1 dephosphorylated ATM Ser1981, a site critical for ATM monomerization and activation, and was critical for resetting ATM phosphorylation as cells repaired damaged DNA. We propose that the Wip1 phosphatase is an integral component of an ATM-dependent signaling pathway. C1 Inst Mol & Cell Biol, Singapore 138673, Singapore. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Kobe Univ, Dept Genome Sci, Fac Med Sci, Chuo Ku, Kobe, Hyogo 6500017, Japan. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Bulavin, DV (reprint author), Inst Mol & Cell Biol, 61 Boplis Dr, Singapore 138673, Singapore. EM dvbulavin@imcb.a-star.edu.sg RI Fornace, Albert/A-7407-2008; ASTAR, IMCB/E-2320-2012; ONISHI, Nobuyuki/L-6296-2013; OI Fornace, Albert/0000-0001-9695-085X; Sathyavageeswaran, Shreeram/0000-0002-6111-1818; Demidov, Oleg/0000-0003-4323-7174 FU Intramural NIH HHS NR 33 TC 178 Z9 187 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP 1 PY 2006 VL 23 IS 5 BP 757 EP 764 DI 10.1016/j.molcel.2006.07.010 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 086HC UT WOS:000240663400014 PM 16949371 ER PT J AU Wu, SL Kim, J Bandle, RW Liotta, L Petricoin, E Karger, BL AF Wu, Shiaw-Lin Kim, Jeongkwon Bandle, Russell W. Liotta, Lance Petricoin, Emanuel Karger, Barry L. TI Dynamic profiling of the post-translational modifications and interaction partners of epidermal growth factor receptor signaling after stimulation by epidermal growth factor using extended range proteomic analysis (ERPA) SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PHASE PROTEIN MICROARRAYS; TANDEM MASS-SPECTROMETRY; GRB2 ADAPTER PROTEIN; SACCHAROMYCES-CEREVISIAE; EXCHANGE FACTOR; LUNG-CANCER; GLYCOSYLATION; COMPLEX; KINASE; PHOSPHORYLATION AB In a recent report, we introduced Extended Range Proteomic Analysis ( ERPA), an intermediate approach between top-down and bottom-up proteomics, for the comprehensive characterization at the trace level ( fmol level) of large and complex proteins. In this study, we extended ERPA to determine quantitatively the temporal changes that occur in the tyrosine kinase receptor, epidermal growth factor receptor ( EGFR), upon stimulation. Specifically A 431 cells were stimulated with epidermal growth factor after which EGFR was immunoprecipitated at stimulation times of 0, 0.5, 2, and 10 min as well as 4 h. High sequence coverage was obtained ( 96%), and methods were developed for label-free quantitation of phosphorylation and glycosylation. A total of 13 phosphorylation sites were identified, and the estimated stoichiometry was determined over the stimulation time points, including Thr( P) and Ser( P) sites in addition to Tyr( P) sites. A total of 10 extracellular domain N-glycan sites were also identified, and major glycoforms at each site were quantitated. No change in the extent of glycosylation with stimulation was observed as expected. Finally potential binding partners to EGFR were identified based on changes in the amount of protein pulled down with EGFR as a function of time of stimulation. Many of the 19 proteins identified are known binding partners of EGFR. This work demonstrates that comprehensive characterization provides a powerful tool to aid in the study of important therapeutic targets. The detailed molecular information will prove useful in future studies in tissue. C1 Northeastern Univ, Barnett Inst, Boston, MA 02125 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA. RP Karger, BL (reprint author), Northeastern Univ, Barnett Inst, Boston, MA 02125 USA. EM b.karger@neu.edu RI Kim, Jeongkwon/C-6230-2012 OI Kim, Jeongkwon/0000-0002-0087-1151 FU Intramural NIH HHS; NIGMS NIH HHS [GM 15847] NR 52 TC 66 Z9 69 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2006 VL 5 IS 9 BP 1610 EP 1627 DI 10.1074/mcp.M600105-MCP200 PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 084RJ UT WOS:000240551800006 PM 16799092 ER PT J AU Pollard, HB Eidelman, O Jozwik, C Huang, W Srivastava, M Ji, XD McGowan, B Norris, CF Todo, T Darling, T Mogayzel, PJ Zeitlin, PL Wright, J Guggino, WB Metcalf, E Driscoll, WJ Mueller, G Paweletz, C Jacobowitz, DM AF Pollard, Harvey B. Eidelman, Ofer Jozwik, Catherine Huang, Wei Srivastava, Meera Ji, Xia D. McGowan, Brighid Norris, Christine Formas Todo, Tsuyoshi Darling, Thomas Mogayzel, Peter J. Zeitlin, Pamela L. Wright, Jerry Guggino, William B. Metcalf, Eleanore Driscoll, William J. Mueller, Greg Paweletz, Cloud Jacobowitz, David M. TI De novo biosynthetic profiling of high abundance proteins in cystic fibrosis lung epithelial cells SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; 2-DIMENSIONAL GEL-ELECTROPHORESIS; NF-KAPPA-B; MASS-SPECTROMETRY; PLASMA-MEMBRANE; CFTR; GENE; IDENTIFICATION; EXPRESSION; PROTEOMICS AB In previous studies with cystic fibrosis ( CF) IB3-1 lung epithelial cells in culture, we identified 194 unique high abundance proteins by conventional two-dimensional gel electrophoresis and mass spectrometry ( Pollard, H. B., Ji, X.-D., Jozwik, C. J., and Jacobowitz, D. M. ( 2005) High abundance protein profiling of cystic fibrosis lung epithelial cells. Proteomics 5, 2210 - 2226). In the present work we compared the IB3-1 cells with IB3-1/S9 daughter cells repaired by gene transfer with AAV-( wild type) CFTR. We report that gene transfer resulted in significant changes in silver stain intensity of only 20 of the 194 proteins. However, simultaneous measurement of de novo biosynthetic rates with [ S-35] methionine of all 194 proteins in both cell types resulted in the identification of an additional 31 CF-specific proteins. Of the 51 proteins identified by this hybrid approach, only six proteins changed similarly in both the mass and kinetics categories. This kinetic portion of the high abundance CF proteome, hidden from direct analysis of abundance, included proteins from transcription and signaling pathways such as NF kappa B, chaperones such as HSC70, cytoskeletal proteins, and others. Connectivity analysis indicated that similar to 30% of the 51-member hybrid high abundance CF proteome interacts with the NF kappa B signaling pathway. In conclusion, measurement of biosynthetic rates on a global scale can be used to identify disease-specific differences within the high abundance cystic fibrosis proteome. Most of these kinetically defined proteins are unaffected in expression level when using conventional silver stain analysis. We anticipate that this novel hybrid approach to discovery of the high abundance CF proteome will find general application to other proteomic problems in biology and medicine. C1 Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Sch Med, Dept Dermatol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Sch Med, Dept Microbiol, Bethesda, MD 20814 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Merck & Co Inc, Whitehouse Stn, NJ 08889 USA. RP Pollard, HB (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM hpollard@usuhs.mil OI Darling, Thomas/0000-0002-5161-1974 FU Intramural NIH HHS; NHLBI NIH HHS [N01-HV 28187]; NIDDK NIH HHS [R01-DK 53051-07]; NIMH NIH HHS [Z01-MH 00388-29] NR 42 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD SEP PY 2006 VL 5 IS 9 BP 1628 EP 1637 DI 10.1074/mcp.M600091-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 084RJ UT WOS:000240551800007 PM 16829594 ER PT J AU Gonzalez-Iglesias, AE Jiang, YH Tomic, M Kretschmannova, K Andric, SA Zemkova, H Stojilkovic, SS AF Gonzalez-Iglesias, Arturo E. Jiang, Yonghua Tomic, Melanija Kretschmannova, Karla Andric, Silvana A. Zemkova, Hana Stojilkovic, Stanko S. TI Dependence of electrical activity and calcium influx-controlled prolactin release on adenylyl cyclase signaling pathway in pituitary lactotrophs SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RAT ANTERIOR-PITUITARY; ACTIVATED CATION CURRENTS; NUCLEOTIDE-GATED CHANNELS; CAPACITATIVE CA2+ ENTRY; PROTEIN-KINASE-C; CYCLIC-AMP; HORMONE SECRETION; INOSITOL 1,4,5-TRISPHOSPHATE; INTRACELLULAR CALCIUM; FEEDBACK INHIBITION AB Pituitary lactotrophs in vitro fire extracellular Ca2+-dependent action potentials spontaneously through still unidentified pacemaking channels, and the associated voltage-gated Ca2+ influx (VGCI) is sufficient to maintain basal prolactin (PRL) secretion high and steady. Numerous plasma membrane channels have been characterized in these cells, but the mechanism underlying their pacemaking activity is still not known. Here we studied the relevance of cyclic nucleotide signaling pathways in control of pacemaking, VGCI, and PRL release. In mixed anterior pituitary cells, both VGCI-inhibitable and -insensitive adenylyl cyclase (AC) subtypes contributed to the basal cAMP production, and soluble guanylyl cyclase was exclusively responsible for basal cGMP production. Inhibition of basal AC activity, but not soluble guanylyl cyclase activity, reduced PRL release. In contrast, forskolin stimulated cAMP and cGMP production as well as pacemaking, VGCI, and PRL secretion. Elevation in cAMP and cGMP levels by inhibition of phosphodiesterase activity was also accompanied with increased PRL release. The AC inhibitors attenuated forskolin-stimulated cyclic nucleotide production, VGCI, and PRL release. The cell-permeable 8-bromo-cAMP stimulated firing of action potentials and PRL release and rescued hormone secretion in cells with inhibited ACs in an extracellular Ca2+-dependent manner, whereas 8-bromo-cGMP and 8-(4-chlorophenyltio)-2'-O-methyl-cAMP were ineffective. Protein kinase A inhibitors did not stop spontaneous and forskolin-stimulated pacemaking, VGCI, and PRL release. These results indicate that cAMP facilitates pacemaking, VGCI, and PRL release in lactotrophs predominantly in a protein kinase A- and Epac cAMP receptor-independent manner. C1 NICHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016 FU Intramural NIH HHS NR 66 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2006 VL 20 IS 9 BP 2231 EP 2246 DI 10.1210/me.2005-0363 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 078SI UT WOS:000240123300020 PM 16645040 ER PT J AU Chandler, RJ Aswani, V Tsai, MS Falk, M Wehrli, N Stabler, S Allen, R Sedensky, M Kazazian, HH Venditti, CP AF Chandler, Randy J. Aswani, Vijay Tsai, Matthew S. Falk, Marni Wehrli, Natasha Stabler, Sally Allen, Robert Sedensky, Margaret Kazazian, Haig H. Venditti, Charles P. TI Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: Evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE propionate metabolism; methylmalonic acidemia; methylmalonyl-CoA epimerase; methylmalonyl-CoA mutase; cobalamin; C. elegans; methylmalonyl-CoA racemase; mass spectrometry; RNA interference; bioinformatics ID PROKARYOTIC GENE ARRANGEMENTS; SACCHAROMYCES-CEREVISIAE; COMPLEMENTATION GROUP; IDENTIFICATION; ACIDEMIA; ACIDURIA; DEFICIENCY; EXPRESSION; COENZYME; MUTASE AB We have utilized Caenorhabditis elegans to study human methylmalonic acidemia. Using bioinformatics, a full complement of mammalian homologues for the conversion of propionyl-CoA to succinyl-CoA in the genome of C. elegans, including propionyl-CoA carboxylase subunits A and B (pcca-1, pccb-1), methylmalonic acidemia cobalamin A complementation group (mmaa-1), co(I)balamin adenosyltransferase (mmab-1), MMACHC (cblc-1), methylmalonyl-CoA epimerase (mce-1) and methylmalonyl-CoA mutase (mmcm-1) were identified. To verify predictions that the entire intracellular adenosylcobalamin metabolic pathway existed and was functional, the kinetic properties of the C. elegans mmcm-1 were examined. RNA interference against mmcm-1, mmab-1, mmaa-1 in the presence of propionic acid revealed a chemical phenotype of increased methylmalonic acid; deletion mutants of mmcm-1, mmab-1 and mce-1 displayed reduced 1-[C-14]-propionate incorporation into macromolecules. The mutants produced increased amounts of methylmalonic acid in the culture medium, proving that a functional block in the pathway caused metabolite accumulation. lentiviral delivery of the C elegans mmcm-1 into fibroblasts derived from a patient with mut degrees class methylmalonic acidemia could partially restore propionate flux. The C elegans mce-1 deletion mutant demonstrates for the first time that a lesion at the epimerase step of methylmalonyl-CoA metabolism can functionally impair flux through the methylmalonyl-CoA mutase pathway and suggests that malfunction of MCEE may cause methylmalonic acidemia in humans. The C. elegans system we describe represents the first lower metazoan model organism of mammalian propionate spectrum disorders and demonstrates that mass spectrometry can be employed to study a small molecule chemical phenotype in C. elegans RNAi and deletion mutants. (c) 2006 Elsevier Inc. All rights reserved. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. CASE Sch Med, Dept Genet, Cleveland, OH 44106 USA. CASE Sch Med, Dept Pediat, Cleveland, OH 44106 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19114 USA. Univ Colorado, Sch Med, Dept Med, Denver, CO 80206 USA. Univ Hosp Cleveland, Dept Anesthesiol, Cleveland, OH 44106 USA. RP Venditti, CP (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov FU Intramural NIH HHS [Z01 HG200318-04, Z99 HG999999]; NIDDK NIH HHS [K08 DK073545, K08 DK073545-01]; NIGMS NIH HHS [R01 GM058881, GM58881] NR 35 TC 15 Z9 25 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2006 VL 89 IS 1-2 BP 64 EP 73 DI 10.1016/j.ymgme.2006.06.001 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 084KT UT WOS:000240532500008 PM 16843692 ER PT J AU Lichter-Konecki, U Farber, LW Cronin, JS Suchy, SF Nussbaum, RL AF Lichter-Konecki, U. Farber, L. W. Cronin, J. S. Suchy, S. F. Nussbaum, R. L. TI The effect of missense mutations in the RhoGAP-homology domain on ocrl1 function SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Lowe syndrome; GTPase activating protein; phosphatidylinositol-4,5-bisphosphate 5-phosphatase ID INOSITOL POLYPHOSPHATE 5-PHOSPHATASE; SYNDROME PROTEIN OCRL1; LOWE-SYNDROME PATIENTS; TRANS-GOLGI NETWORK; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; OCULOCEREBRORENAL SYNDROME; GTPASE; GENE; ARF; DEFICIENCY AB Lowe syndrome is a rare X-linked disease characterized by congenital cataracts, defects in renal tubule cell function, and mental retardation. Mutations in the OCRL1 gene, which encodes ocrl1, a phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P-2) 5-phosphatase, are the cause of Lowe syndrome. PtdIns(4,5)P-2, a substrate of ocrl1, is an important signaling molecule within the cell. OCRL1 is ubiquitously expressed and co-localizes with the trans-Golgi network (TGN) and endosomal proteins. The ocrl1 protein contains two recognizable domains, one a conserved Ptd(4,5)P-2 5-phosphatase domain and the other with homology to Rho GTPase activating proteins (RhoGAPs). The objective of our study was to further characterize the ocrl1 RhoGAP-homology domain by analyzing the effect of two missense mutations in this domain, I751N and A780P, which were previously reported in Lowe syndrome patients. Both mutant proteins were expressed at levels similar to wild-type but their enzyme activity was reduced by 85-90%, indicating that the RhoGAP-homology domain is important for the enzymatic function of ocrl1. Study of a C-terminal region of wild-type ocrl1 containing this domain detected no GAP activity, eliminating the possibility of an effect by mutations in this domain on GTPase activation. Because members of the Arf family of small G-proteins are directly involved in (Ptd(4,5)P2) signaling and localize to the TGN like ocrl1, we analyzed by immunoprecipitation the interaction of ocrl1 with Arf1 and Arf6 via its RhoGAP-homology domain. Wild-type ocrl1, but not the I751N mutant protein, co-immunoprecipitated with these two Arf proteins. These results indicate that wild-type ocrl1 and Arf proteins can interact and that this interaction is disrupted by the mutation. It remains unknown whether a disrupted interaction between Arf and ocrl1 plays a role in the Lowe syndrome phenotype. (c) 2006 Elsevier Inc. All rights reserved. C1 Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, 111 Michigan Ave, Washington, DC 20010 USA. EM nussbaumr@humgen.ucsf.edu FU Intramural NIH HHS NR 31 TC 29 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2006 VL 89 IS 1-2 BP 121 EP 128 DI 10.1016/j.ymgme.2006.04.005 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 084KT UT WOS:000240532500016 PM 16777452 ER PT J AU Kulakova, L Singer, SM Conrad, J Nash, TE AF Kulakova, Liudmila Singer, Steven M. Conrad, John Nash, Theodore E. TI Epigenetic mechanisms are involved in the control of Giardia lamblia antigenic variation SO MOLECULAR MICROBIOLOGY LA English DT Article ID SURFACE PROTEIN VSP; INFECTED ERYTHROCYTE; PRIMITIVE EUKARYOTE; GENE FAMILY; IDENTIFICATION; EXPRESSION; PROMOTER; ELEMENTS; GENOME AB Giardia lamblia, an intestinal dwelling protozoan parasite, undergoes surface antigenic variation where only one of an estimated 150 variant-specific surface proteins (VSPs) is expressed and present on the surface at any one time. Transcriptional switching between VSPs results in replacement of one VSP by another. The mechanisms that control antigenic variation are poorly understood and difficult to study because there are multiple copies of each VSP and strong similarity with other VSPs. In order to study transcriptional regulation of one specific vsp, a haemagglutinin (HA) epitope-tagged h7 was integrated into the G. lamblia GS genome. We show that HA-tagged H7 undergoes antigenic variation in the same manner as native H7, also present in the GS genome. Control of expression of both HA-tagged H7 and native H7 is independent of each other even though the genes and their surrounding 5' and 3' flanking sequences are virtually identical. Analysis of expressing and non-expressing clones revealed an absence of HA-tagged h7 gene rearrangements upon switching and acetylation of histone lysine residues within the 167 nucleotides 5' to the expressed HA-tagged h7 gene. Lack of vsp rearrangements and acetylation of expressed immediate upstream regions implicates involvement of epigenetic mechanisms in antigenic variation. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Biol, Washington, DC 20057 USA. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov OI Singer, Steven/0000-0001-5719-7535 NR 32 TC 41 Z9 46 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2006 VL 61 IS 6 BP 1533 EP 1542 DI 10.1111/j.1365-2958.2006.05345.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 082DX UT WOS:000240368000016 PM 16968226 ER PT J AU Kikuchi, R Kusuhara, H Hattori, N Shiota, K Kim, I Gonzalez, FJ Sugiyama, Y AF Kikuchi, Ryota Kusuhara, Hiroyuki Hattori, Naka Shiota, Kunio Kim, Insook Gonzalez, Frank J. Sugiyama, Yuichi TI Regulation of the expression of human organic anion transporter 3 by hepatocyte nuclear factor 1 alpha/beta and DNA methylation SO MOLECULAR PHARMACOLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; GENE-EXPRESSION; CHOROID-PLEXUS; RENAL UPTAKE; KIDNEY; MOUSE; RAT; PROMOTER; SLC22A8; HNF1 AB Human organic anion transporter 3 (hOAT3/SLC22A8) is predominantly expressed in the proximal tubules of the kidney and plays a major role in the urinary excretion of a variety of organic anions. The promoter region of hOAT3 was characterized to elucidate the mechanism underlying the tissue-specific expression of hOAT3. The minimal promoter of hOAT3 was identified to be located approximately 300 base pairs upstream of the transcriptional start site, where there are canonical TATA and hepatocyte nuclear factor (HNF1) binding motifs, which are conserved in the rodent Oat3 genes. Transactivation assays revealed that HNF1 alpha and HNF1 beta markedly increased hOAT3 promoter activity, where the transactivation potency of HNF1 beta was lower than that of HNF1 alpha. Mutations in the HNF1 binding motif prevented the transactivation. Electrophoretic mobility shift assays demonstrated binding of the HNF1 alpha/HNF1 alpha homodimer or HNF1 alpha/HNF1 beta heterodimer to the hOAT3 promoter. It was also demonstrated that the promoter activity of hOAT3 is repressed by DNA methylation. Moreover, the expression of hOAT3 was activated de novo by forced expression of HNF1 alpha alone or both HNF1 alpha and HNF1 beta together with the concomitant DNA demethylation in human embryonic kidney 293 cells that lack expression of endogenous HNF1 alpha and HNF1 beta, whereas forced expression of HNF1 beta alone could not activate the expression of hOAT3. This suggests a synergistic action of the HNF1 alpha/HNF1 beta homodimer or HNF1 alpha/HNF1 beta heterodimer and DNA demethylation for the constitutive expression of hOAT3. These results indicate that the tissue-specific expression of hOAT3 might be regulated by the concerted effect of genetic (HNF1 alpha and HNF1 beta) and epigenetic (DNA methylation) factors. C1 Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Bunkyo Ku, Tokyo 1130033, Japan. Univ Tokyo, Lab Cellular Biochem, Dept Anim Resource Sci Vet Med Sci, Tokyo 1130033, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Sugiyama, Y (reprint author), Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM sugiyama@mol.f.u-tokyo.ac.jp NR 36 TC 62 Z9 66 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2006 VL 70 IS 3 BP 887 EP 896 DI 10.1124/mol.106.025494 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075YA UT WOS:000239922300013 PM 16793932 ER PT J AU Byun, HS Park, KA Won, M Yang, KJ Shin, S Piao, L Kwak, JY Lee, ZW Park, J Seok, JH Liu, ZG Hur, GM AF Byun, Hee Sun Park, Kyeong Ah Won, Minho Yang, Keum-Jin Shin, Sanghee Piao, Longzhen Kwak, Jin Young Lee, Zee-Won Park, Jongsun Seok, Jeong Ho Liu, Zheng-Gang Hur, Gang Min TI Phorbol 12-myristate 13-acetate protects against tumor necrosis factor (TNF)-induced necrotic cell death by modulating the recruitment of TNF receptor 1-associated death domain and receptor-interacting protein into the TNF receptor 1 signaling complex: Implication for the regulatory role of protein kinase C SO MOLECULAR PHARMACOLOGY LA English DT Article ID NF-KAPPA-B; LIGAND-INDUCED APOPTOSIS; FACTOR-ALPHA; POLY(ADP-RIBOSE) POLYMERASE; ISCHEMIA-REPERFUSION; MEDIATED APOPTOSIS; L929 CELLS; T-CELLS; ACTIVATION; INHIBITION AB Protein kinase C (PKC) triggers cellular signals that regulate proliferation or death in a cell- and stimulus-specific manner. Although previous studies have demonstrated that activation of PKC with phorbol 12-myristate 13-acetate (PMA) protects cells from apoptosis induced by a number of mechanisms, including death receptor ligation, little is known about the effect or mechanism of PMA in the necrotic cell death. Here, we demonstrate that PMA-mediated activation of PKC protects against tumor necrosis factor (TNF)-induced necrosis by disrupting formation of the TNF receptor (TNFR) 1 signaling complex. Pretreatment with PMA protected L929 cells from TNF-induced necrotic cell death in a PKC-dependent manner, but it did not protect against DNA-damaging agents, including doxorubicin (Adriamycin) and camptothecin. Analysis of the upstream signaling events affected by PMA revealed that it markedly inhibited the TNF-induced recruitment of TNFR1-associated death domain TRADD) and receptor-interacting protein (RIP) to TNFR1, subsequently inhibiting TNF-induced activation of nuclear factor-kappa B and c-Jun NH2-terminal kinase (JNK). However, JNK inhibitors do not significantly affect TNF-induced necrosis, suggesting that the inhibition of JNK activation by PMA is not part of the antinecrotic mechanism. In addition, PMA acted as an antagonist of TNF-induced reactive oxygen species (ROS) production, thereby suppressing activation of ROS-mediated poly(ADP-ribose) polymerase (PARP), and thus inhibiting necrotic cell death. Furthermore, during TNF-induced necrosis, PARP was significantly activated in wild-type mouse embryonic fibroblast (MEF) cells but not in RIP-/- or TNFR-associated factor 2-/- MEF cells. Taken together, these results suggest that PKC activation ensures effective shutdown of the death receptor-mediated necrotic cell death pathway by modulating formation of the death receptor signaling complex. C1 Chungnam Natl Univ, Coll Med, Dept Pharmacol, Taejon 301131, South Korea. Chungnam Natl Univ, Coll Med, Inst Canc Res, Taejon 301131, South Korea. Korea Basic Sci Inst, Div Proteome Res, Glycom Team, Taejon, South Korea. Natl Canc Inst, Cell & Cellular Biol Branch, Canc Res Ctr, NIH, Bethesda, MD USA. RP Hur, GM (reprint author), Chungnam Natl Univ, Coll Med, Dept Pharmacol, 6 Munhwa Dong,Jung Gu, Taejon 301131, South Korea. EM gmhur@cnu.ac.kr NR 40 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2006 VL 70 IS 3 BP 1099 EP 1108 DI 10.1124/mol.106.025452 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075YA UT WOS:000239922300034 PM 16798936 ER PT J AU Antony, S Agama, KK Miao, ZH Hollingshead, M Holbeck, SL Wright, MH Varticovski, L Nagarajan, M Morrell, A Cushman, M Pommier, Y AF Antony, Smitha Agama, Keli K. Miao, Ze-Hong Hollingshead, Melinda Holbeck, Susan L. Wright, Mollie H. Varticovski, Lyuba Nagarajan, Muthukaman Morrell, Andrew Cushman, Mark Pommier, Yves TI Bisindenoisoquinoline bis-1,3-{(5,6-dihydro-5,11-diketo-11H-indeno[1,2-c] isoquinoline)-6-propylamino}propane bis(trifluoroacetate) (NSC 727357), a DNA intercalator and topoisomerase inhibitor with antitumor activity SO MOLECULAR PHARMACOLOGY LA English DT Article ID DIOL EPOXIDE ADDUCTS; BREAST-CANCER CELLS; I INHIBITORS; CLEAVAGE COMPLEXES; BIOLOGICAL EVALUATION; MJ-III-65 NSC-706744; ANTICANCER AGENTS; COVALENT COMPLEX; CARCINOMA-CELLS; G(2) ARREST AB Indenoisoquinolines are topoisomerase (Top) I inhibitors developed to overcome some of the limitations of camptothecins and expand their anticancer spectrum. Bis-1,3-{(5,6-dihydro5,11-diketo-11H-indeno[1,2-c] isoquinoline)-6-propylamino}propane bis(trifluoroacetate) (NSC 727357) is a novel dimeric indenoisoquinoline derivative with potent antiproliferative activity in the NCI-60 cell line panel, promising hollow fiber activity (score of 32) and activity against xenografts. Submicromolar concentrations of the bisindenoisoquinoline NSC 727357 induce Top1 cleavage complexes at specific sites in biochemical assays. At higher concentrations, inhibition of Top1 catalytic activity and DNA intercalation is observed. NSC 727357 also induces a limited number of Top2-DNA cleavage complexes. In contrast to the effect of other Top1 inhibitors, cells treated with the bisindenoisoquinoline NSC 727357 show an arrest of cell cycle progression in G 1 with no significant inhibition of DNA synthesis after a short exposure to the drug. Moreover, unlike camptothecin and the indenoisoquinoline MJ-III-65 (NSC 706744, 6-[3-(2-hydroxyethyl) aminopropyl]-5,6-dihydro-5,11-diketo-2,3-dimethoxy-(methylenedioxy)-11H-indeno[1,2c] isoquinoline hydrochloride), the cytotoxicity of bisindenoisoquinoline NSC 727357 is only partially dependent on Top1 and p53, indicating that this drug has additional targets besides Top1 and Top2. C1 NCI, Canc Res Ctr, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Informat Technol Branch, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. RP Pommier, Y (reprint author), NCI, Canc Res Ctr, Mol Pharmacol Lab, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, ST32-CA09634-12, U01-CA89566]; PHS HHS [C06-14499] NR 51 TC 32 Z9 32 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2006 VL 70 IS 3 BP 1109 EP 1120 DI 10.1124/mol.106.024372 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075YA UT WOS:000239922300035 PM 16798938 ER PT J AU Wendland, JR Kruse, MR Murphy, DL AF Wendland, J. R. Kruse, M. R. Murphy, D. L. TI Functional SLITRK1 var321, varCDfs and SLC6A4 G56A variants and susceptibility to obsessive-compulsive disorder SO MOLECULAR PSYCHIATRY LA English DT Letter ID SEQUENCE VARIANTS; TRANSPORTER; SUPPORT; AUTISM; LOCI C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Wendland, JR (reprint author), NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. EM wendlandj@mail.nih.gov RI Wendland, Jens/A-1809-2012 FU Intramural NIH HHS NR 13 TC 39 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2006 VL 11 IS 9 BP 802 EP 804 DI 10.1038/sj.mp.4001848 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 077PW UT WOS:000240043100004 PM 16936762 ER PT J AU Ducci, F Newman, TK Funt, S Brown, GL Virkkunen, M Goldman, D AF Ducci, F. Newman, T. K. Funt, S. Brown, G. L. Virkkunen, M. Goldman, D. TI A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index SO MOLECULAR PSYCHIATRY LA English DT Article DE MAOA; BMI; HVA; dopamine; alcoholism; ASPD ID MONOAMINE-OXIDASE-A; DEFICIT HYPERACTIVITY DISORDER; CEREBROSPINAL-FLUID; HOMOVANILLIC-ACID; 5-HYDROXYINDOLEACETIC ACID; METABOLITE CONCENTRATIONS; REGULATORY POLYMORPHISM; AGGRESSIVE-BEHAVIOR; SEROTONIN FUNCTION; SUICIDAL-BEHAVIOR AB Variation in brain monoaminergic activity is heritable and modulates risk of alcoholism and other addictions, as well as food intake and energy expenditure. Monoamine oxidase A deaminates the monoamine neurotransmitters serotonin, dopamine (DA), and noradrenalin. The monoamine oxidase A (MAOA) gene (Xp11.5) contains a length polymorphism in its promoter region (MAOA-LPR) that putatively affects transcriptional efficiency. Our goals were to test (1) whether MAOA-LPR contributes to interindividual variation in monoamine activity, assessed using levels of cerebrospinal fluid (CSF) monoamine metabolites; and (2) whether MAOA-LPR genotype influences alcoholism and/ or body mass index (BMI). Male, unrelated criminal alcoholics (N = 278) and controls (N = 227) were collected from a homogeneous Finnish source population. CSF concentration of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were available from 208 participants. Single allele, hemizygous genotypes were grouped according to inferred effect of the MAOA alleles on transcriptional activity. MAOA-LPR genotypes had a significant effect on CSF HVA concentration (P = 0.01) but explained only 3% of the total variance. There was a detectable but nonsignificant genotype effect on 5-HIAA and no effects on MHPG. Specifically, the genotype conferring high MAOA activity was associated with lower HVA levels in both alcoholics and controls, a finding that persisted after accounting for the potential confounds of alcoholism, BMI, height, and smoking. MAOA-LPR genotype predicted BMI (P < 0.005), with the high-activity genotype being associated with lower BMI. MAOA-LPR genotypes were not associated with alcoholism or related psychiatric phenotypes in this data set. Our results suggest that MAOA-LPR allelic variation modulates DA turnover in the CNS, but does so in a manner contrary to our prior expectation that alleles conferring high activity would predict higher HVA levels in CSF. Our results are consistent with an emerging literature that suggests greater complexity in how variation in MAOA expression alters monoaminergic function. Finally, our work suggests that MAOA may be involved in the regulation of BMI. Independent samples are necessary to confirm this preliminary finding. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Univ Virginia, Charlottesville, VA USA. Univ Helsinki, Helsinki, Finland. RP Ducci, F (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S-32, Rockville, MD 20852 USA. EM ducci@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 51 TC 38 Z9 41 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2006 VL 11 IS 9 BP 858 EP 866 DI 10.1038/sj.mp.4001856 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 077PW UT WOS:000240043100009 PM 16770335 ER PT J AU Meyer-Lindenberg, A Nichols, T Callicott, JH Ding, J Kolachana, B Buckholtz, J Mattay, VS Egan, M Weinberger, DR AF Meyer-Lindenberg, A. Nichols, T. Callicott, J. H. Ding, J. Kolachana, B. Buckholtz, J. Mattay, V. S. Egan, M. Weinberger, D. R. TI Impact of complex genetic variation in COMT on human brain function SO MOLECULAR PSYCHIATRY LA English DT Article DE COMT; n-back; haplotypes; prefrontal cortex; schizophrenia; fMRI ID O-METHYLTRANSFERASE COMT; PREFRONTAL CORTEX; WORKING-MEMORY; LINKAGE DISEQUILIBRIUM; RESPONSE-INHIBITION; PROMOTER REGION; GENOTYPE DATA; HUMAN GENOME; SCHIZOPHRENIA; ASSOCIATION AB Catechol-O-methyltransferase (COMT) has been shown to be critical for prefrontal dopamine flux, prefrontal cortex-dependent cognition and activation. Several potentially functional variants in the gene have been identified, but considerable controversy exists regarding the contribution of individual alleles and haplotypes to risk for schizophrenia, partly because clinical phenotypes are ill-defined and preclinical studies are limited by lack of adequate models. Here, we propose a neuroimaging approach to overcome these limitations by characterizing the functional impact of ambiguous haplotypes on a neural system-level intermediate phenotype in humans. Studying 126 healthy control subjects during a workingmemory paradigm, we find that a previously described risk variant in a functional Val158Met (rs4680) polymorphism interacts with a P2 promoter region SNP (rs2097603) and an SNP in the 30 region (rs165599) in predicting inefficient prefrontal working memory response. We report evidence that the nonlinear response of prefrontal neurons to dopaminergic stimulation is a neural mechanism underlying these nonadditive genetic effects. This work provides an in vivo approach to functional validation in brain of the biological impact of complex genetic variations within a gene that may be critical for its clinical association. C1 NIMH, Neuroimaging Core Facil, NIH, DHHS, Bethesda, MD 20892 USA. NIMH, Unit Syst Neurosci Psychiat, NIH, DHHS, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, DHHS,Cognit & Psychosis Program, Bethesda, MD 20892 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Neuroimaging Core Facil, NIH, DHHS, 10-3C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov RI Ding, Jun/G-3918-2011; Buckholtz, Joshua /E-7299-2010; Callicott, Joseph/C-9102-2009; OI Buckholtz, Joshua /0000-0002-9418-8686; Callicott, Joseph/0000-0003-1298-3334; Nichols, Thomas/0000-0002-4516-5103; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 49 TC 205 Z9 208 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2006 VL 11 IS 9 BP 867 EP 877 DI 10.1038/sj.mp.4001860 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 077PW UT WOS:000240043100010 PM 16786032 ER PT J AU Misamore, MJ Stein, KK Lynn, JW AF Misamore, Michael J. Stein, Katheryn K. Lynn, John W. TI Sperm incorporation and pronuclear development during fertilization in the freshwater bivalve Dreissena polymorpha SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE bivalve; sperm; flagellum; pronucleus; mitochondria ID PLASMA-MEMBRANE COMPONENTS; ZEBRA MUSSEL; MEIOTIC MATURATION; ALPHA-TUBULIN; CHROMATIN DECONDENSATION; NUCLEAR TRANSFORMATIONS; PATERNAL MITOCHONDRION; ELECTRON-MICROSCOPY; EARLY EMBRYOGENESIS; MIDDLE-PIECE AB The invasive zebra mussel, Dreissena polymorpha (D. polymorpha), is proving to be a valuable model for understanding general mechanisms of fertilization, particularly regarding sperm incorporation. In the present study, we tracked the various components of the fertilizing sperm of D. polymorpha during sperm incorporation. During fertilization the sperm membrane remains associated with the egg surface as a distinct patch that disperses over time. This patch marked the site of sperm entry that occurs predominately on the CD blastomere. Taking advantage of the relatively unpigmented cytoplasm, real-time observations were made of the incorporated sperm nucleus as it decondensed and reformed as a developing pronucleus. Pronuclear enlargement occurred progressively and at rates comparable with previously reported fixed-time point observations. Sperm mitochondria were. incorporated and separated from the sperm along the leading edge of the decondensing nucleus. Sperm mitochondria labeled with Mitotracker Green((R)) remained predominately associated with the CD blastomere following first cleavage and could be tracked to the 16-cell stage before the fluorescence was too faint to detect. Additionally, the demembranated sperm axoneme was incorporated, separated during nuclear decondensation, and remained visible in the egg cytoplasm up to 30 min postinsemination (PI). The present study provides one of the most complete descriptions of incorporation on multiple sperm components into the egg and coordinates fixed-time point observations with real-time observations of sperm within the remarkably transparent egg cytoplasm of zebra mussels. C1 Texas Christian Univ, Dept Biol, Ft Worth, TX 76129 USA. NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Misamore, MJ (reprint author), Texas Christian Univ, Dept Biol, TCU Box 298930, Ft Worth, TX 76129 USA. EM m.misamore@tcu.edu RI Lynn, John/B-3126-2013 NR 61 TC 5 Z9 5 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD SEP PY 2006 VL 73 IS 9 BP 1140 EP 1148 DI 10.1002/mrd.20415 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 068BX UT WOS:000239347800008 PM 16736529 ER PT J AU Hansen, L Yao, WL Eiberg, H Funding, M Riise, R Kjaer, K Hejtmancik, J Rosenberg, T AF Hansen, Lars Yao, Wenliang Eiberg, Hans Funding, Mikkel Riise, Ruth Kjaer, Klaus Wilbrandt Hejtmancik, James Fielding Rosenberg, Thomas TI The congenital "ant-egg" cataract phenotype is caused by a missense mutation in connexin46 SO MOLECULAR VISION LA English DT Article ID NUCLEAR PULVERULENT CATARACT; GENE; LINKAGE AB PURPOSE: "Ant-egg" cataract is a rare, distinct variety of congenital/infantile cataract that was reported in a large Danish family in 1967. This cataract phenotype is characterized by ant-egg-like bodies embedded in the lens in a laminar configuration and is inherited as an autosomal dominant trait. We retrieved the family and performed linkage analysis to determine the disease locus and identify the mutated gene. METHODS: The family (CC00103) was identified in a National Register of Hereditary Eye Diseases and updated based on The Danish Civil Register System. Genome wide linkage analysis and haplotyping using STS marker systems were carried out to achieve a LOD score above 3. The disease-causing candidate gene was sequenced and the mutation was identified and verified by restriction enzyme digestion of genomic DNA from all individuals in family CC00103 and 60 healthy controls. RESULTS: Linkage analysis resulted in a LOD score of 3.91 for marker D13S1275 located close to the known cataract gene GJA3. A novel missense mutation c.32T > C (L11S), was found by sequencing DNA from two affected members. The mutation was present in all affected individuals and was neither found in unaffected family members nor in 60 healthy individuals by restriction enzyme digests. CONCLUSIONS: The congenital "ant-egg" cataract phenotype is caused by a L11S mutation in connexin46 (Cx46) located in the signal peptide domain. Further studies are needed to unravel the mechanism leading to the formation of the "ant-eggs". C1 Kennedy Inst Natl Eye Clin, Gordon Norrie Ctr Genet Eye Dis, DK-2900 Hellerup, Denmark. Univ Copenhagen, Inst Med Biochem & Genet, Wilhelm Johannsen Ctr Funct Genome Res, DK-1168 Copenhagen, Denmark. Univ Copenhagen, Panum Inst, Inst Med Biochem & Genet, Dept G, DK-1168 Copenhagen, Denmark. NEI, Sect Ophthalm Mol Genet, NIH, Bethesda, MD 20892 USA. Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus, Denmark. Univ Hosp, Rikshosp, Dept Med Genet, Oslo, Norway. RP Rosenberg, T (reprint author), Kennedy Inst Natl Eye Clin, Gordon Norrie Ctr Genet Eye Dis, 1 Rymarksvej, DK-2900 Hellerup, Denmark. EM roseeye@visaid.dk NR 23 TC 34 Z9 35 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD SEP 1 PY 2006 VL 12 IS 116 BP 1033 EP 1039 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 083ON UT WOS:000240468200001 PM 16971895 ER PT J AU Bara-Jimenez, W Dimitrova, TD Sherzai, A Aksu, M Chase, TN AF Bara-Jimenez, William Dimitrova, Tzvetelina D. Sherzai, Abdullah Aksu, Murat Chase, Thomas N. TI Glutamate release inhibition ineffective in levodopa-induced motor complications SO MOVEMENT DISORDERS LA English DT Article DE glutamate; riluzole; dopamine; Parkinson's disease; dyskinesias; levodopa; striatum ID ADVANCED PARKINSONS-DISEASE; INDUCED DYSKINESIAS; PRIMATE MODEL; DOUBLE-BLIND; RILUZOLE; RATS; ANTAGONIST; MECHANISMS; RECEPTORS; NEURONS AB Reported benefits of various glutamatergic receptor antagonists in Parkinson's disease (PD) prompted an evaluation of the antidyskinetic effect of a putative glutamate release inhibitor in 15 moderately advanced patients. In a 3-week, double-blind, proof-of-concept study, riluzole (200 mg/day) failed to alter parkinsonian or levodopa-induced motor complication severity. Opposing effects of a generalized inhibition of glutamate-mediated synaptic transmission may limit the usefulness of this approach to treat PD. (c) 2006 Movement Disorder Society. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Bara-Jimenez, W (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C103, Bethesda, MD 20892 USA. EM baraw@ninds.nih.gov FU Intramural NIH HHS NR 21 TC 18 Z9 18 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2006 VL 21 IS 9 BP 1380 EP 1383 DI 10.1002/mds.20976 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 091AO UT WOS:000240998100013 PM 16758479 ER PT J AU Calabrese, M Morra, A Romualdi, C Bernardi, V Atzori, M Rinaldi, L McAuliffe, M Reynolds, R Barachino, L Perini, P Fischl, B Gallo, P AF Calabrese, M. Morra, A. Romualdi, C. Bernardi, V. Atzori, M. Rinaldi, L. McAuliffe, M. Reynolds, R. Barachino, L. Perini, P. Fischl, B. Gallo, P. TI Cortical atrophy is relevant in multiple sclerosis at clinical onset SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 Multiple Sclerosis Ctr, Padua, Italy. Euganea Med, Padua, Italy. CRIBI, Padua, Italy. NIH, Biomed Imaging Res Serv Sect, Bethesda, MD USA. NIH, NIMH, Bethesda, MD USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. RI Romualdi, Chiara/K-1132-2016 OI Romualdi, Chiara/0000-0003-4792-9047 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S172 EP S173 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400570 ER PT J AU Calabrese, M Bernardi, V Atzori, M Rinaldi, L Morra, A Romualdi, C McAuliffe, M Barachino, L Perini, P Fischl, B Gallo, P AF Calabrese, M. Bernardi, V. Atzori, M. Rinaldi, L. Morra, A. Romualdi, C. McAuliffe, M. Barachino, L. Perini, P. Fischl, B. Gallo, P. TI Cortical lesions appear early, are frequent and clinically relevant in multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 Multiple Sclerosis Ctr, Padua, Italy. Eugenea Med, Padua, Italy. CRIBI, Padua, Italy. NIH, Biomed Imaging Res Serv Sect, Bethesda, MD USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. RI Romualdi, Chiara/K-1132-2016 OI Romualdi, Chiara/0000-0003-4792-9047 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S2 EP S3 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400007 ER PT J AU Chiu, AW Ehrmantraut, M Richert, N Ohayon, J Cantor, F Frank, J McFarland, H Bagnato, F AF Chiu, A. W. Ehrmantraut, M. Richert, N. Ohayon, J. Cantor, F. Frank, J. McFarland, H. Bagnato, F. TI A longitudinal 36 monthly imaging study on the effect of NAb in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 NINDS NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S201 EP S202 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400662 ER PT J AU Chiu, AW Auh, S Calabrese, M Cao, M Ohayon, J Tovar-Moll, F Ostuni, J Cantor, F McFarland, H Bagnato, F AF Chiu, A. W. Auh, S. Calabrese, M. Cao, M. Ohayon, J. Tovar-Moll, F. Ostuni, J. Cantor, F. McFarland, H. Bagnato, F. TI Does an anatomical gradient of cortical disease exist in patients with relapsing-remitting multiple sclerosis? SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 NIH, NINDS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S177 EP S178 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400585 ER PT J AU Durastanti, V Pellegrini, S Ostuni, J Tovar-Moll, F Chiu, AW Ohayon, J Ehrmantraut, M Auh, S McFarland, H Bagnato, F AF Durastanti, V. Pellegrini, S. Ostuni, J. Tovar-Moll, F. Chiu, A. W. Ohayon, J. Ehrmantraut, M. Auh, S. McFarland, H. Bagnato, F. TI Grey matter disease in patients with multiple sclerosis imaged at high field: correlation between cortical and subcortical pathology SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S44 EP S45 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400144 ER PT J AU Lovas, G Nielsen, J Hudson, L AF Lovas, G. Nielsen, J. Hudson, L. TI Neuronal response to experimental demyelination and axonal transection - A microarray study SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 Jahn Ferenc Hosp, Budapest, Hungary. Natl Inst Hlth, Bethesda, MD USA. RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S48 EP S49 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400156 ER PT J AU Riva, M Ikonomidou, VN Ostuni, J van Gelderen, P Tasciyan, T Tovar-Moll, F Chiu, AW Ohayon, JM Ehrmantraut, M Duyn, JH McFarland, HF Bagnato, F AF Riva, M. Ikonomidou, V. N. Ostuni, J. van Gelderen, P. Tasciyan, T. Tovar-Moll, F. Chiu, A. W. Ohayon, J. M. Ehrmantraut, M. Duyn, J. H. McFarland, H. F. Bagnato, F. TI 3T tissue specific imaging to characterise in vivo chronic black holes in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 22nd Congress of the European-Committee-for-the-Treatment-and-Resarch-in-Multiple-Sclerosis CY SEP 27-30, 2006 CL Madrid, SPAIN SP European Comm Treatment & Res Multiple Sclerosis C1 Natl Inst Hlth, Bethesda, MD USA. RI Duyn, Jozef/F-2483-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2006 VL 12 SU 1 BP S44 EP S44 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 103XV UT WOS:000241921400143 ER PT J AU Bischoff, JF Rehner, SA Humber, RA AF Bischoff, Joseph F. Rehner, Stephen A. Humber, Richard A. TI Metarhizium frgidum sp nov.: a cryptic species of M-anisopliae and a member of the M-flavoviride complex SO MYCOLOGIA LA English DT Article DE biocontrol; Clavicipitaceae; Cordyceps; cryptic species; entomopathogen ID EVOLUTION AB The anamorph genus Metarhizium is composed of arthropod pathogens, several with broad geographic and host ranges. Members of the genus, including "M. anisopliae var. frigidum" nomen nudum and Metarhizium flavoviride, have been used as biological insecticides. In a recent revision of the genus the variety "M. anisopliae var. frigidum" was suggested to be a synonym of M. flavoviride based largely on ITS sequence phylogenetic analysis. In this study we conducted morphological evaluations and multigene phylogenetic analyses with EF-1 alpha, RPB1 and RPB2 for strains of M. flavoviride and "M. anisopliae var. frigidum." Included in these evaluations were the ex-type of ill. flavoviride var. flavoviride and what likely would be considered the "ex-type" of the invalidly published taxon "M. anisopliae var. frigidum". Based on morphological and molecular evidence we conclude that "M. anisopliae var. frigidum" is distinct from M. flavoviride and the taxon M. frigidum sp. nov. is described. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. USDA, ARS, Insect Biocontrol Lab, BARC W, Beltsville, MD 20705 USA. USDA, ARS, Plant Soil & Nutrit Lab, Ithaca, NY 14853 USA. RP Bischoff, JF (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20894 USA. EM bischoff@ncbi.nlm.nih.gov NR 21 TC 40 Z9 42 U1 0 U2 7 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD SEP-OCT PY 2006 VL 98 IS 5 BP 737 EP 745 DI 10.3852/mycologia.98.5.737 PG 9 WC Mycology SC Mycology GA 125JP UT WOS:000243438500008 PM 17256577 ER PT J AU Khanna, C Lindblad-Toh, K Vail, D London, C Bergman, P Barber, L Breen, M Kitchell, B McNeil, E Modiano, JF Niemi, S Comstock, KE Ostrander, E Westmoreland, S Withrow, S AF Khanna, Chand Lindblad-Toh, Kerstin Vail, David London, Cheryl Bergman, Philip Barber, Lisa Breen, Matthew Kitchell, Barbara McNeil, Elizabeth Modiano, Jaime F. Niemi, Steven Comstock, Kenine E. Ostrander, Elaine Westmoreland, Susan Withrow, Stephen TI The dog as a cancer model SO NATURE BIOTECHNOLOGY LA English DT Letter C1 NCI, Ctr Canc Res, Comparat Oncol Program, Rockville, MD 20815 USA. MIT, Cambridge, MA 02141 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. Colorado State Univ, Anim Canc Ctr, Ft Collins, CO 80523 USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. Anim Med Ctr, New York, NY 10021 USA. Tufts Univ, Sch Vet Med, Dept Clin Sci, North Grafton, MA 01536 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Michigan State Univ, Ctr Comparat Oncol, E Lansing, MI 48824 USA. Univ Minnesota, Dept Vet Clin Sci, St Paul, MN 55108 USA. Univ Colorado, Integrated Dept Immunol, Denver, CO 80214 USA. Univ Colorado, AMC Canc Res Ctr, Denver, CO 80214 USA. Hlth Sci Ctr, Denver, CO 80214 USA. Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA 02129 USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, Comparat Oncol Program, 9610 Med Ctr Dr,Room 315, Rockville, MD 20815 USA. EM khannac@mail.nih.gov; kersli@broad.mit.edu RI London, Cheryl/E-6561-2012 NR 2 TC 143 Z9 147 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1065 EP 1066 DI 10.1038/nbt0906-1065b PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200014 PM 16964204 ER PT J AU Patterson, TA Lobenhofer, EK Fulmer-Smentek, SB Collins, PJ Chu, TM Bao, WJ Fang, H Kawasaki, ES Hager, J Tikhonova, IR Walker, SJ Zhang, LA Hurban, P de Longueville, F Fuscoe, JC Tong, WD Shi, LM Wolfinger, RD AF Patterson, Tucker A. Lobenhofer, Edward K. Fulmer-Smentek, Stephanie B. Collins, Patrick J. Chu, Tzu-Ming Bao, Wenjun Fang, Hong Kawasaki, Ernest S. Hager, Janet Tikhonova, Irina R. Walker, Stephen J. Zhang, Liang Hurban, Patrick de Longueville, Francoise Fuscoe, James C. Tong, Weida Shi, Leming Wolfinger, Russell D. TI Performance comparison of one-color and two-color platforms within the MicroArray Quality Control (MAQC) project SO NATURE BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE MICROARRAYS; COMPARABILITY; TECHNOLOGIES; PATTERNS AB Microarray-based expression profiling experiments typically use either a one-color or a two-color design to measure mRNA abundance. The validity of each approach has been amply demonstrated. Here we provide a simultaneous comparison of results from one- and two-color labeling designs, using two independent RNA samples from the MicroArray Quality Control (MAQC) project, tested on each of three different microarray platforms. The data were evaluated in terms of reproducibility, specificity, sensitivity and accuracy to determine if the two approaches provide comparable results. For each of the three microarray platforms tested, the results show good agreement with high correlation coefficients and high concordance of differentially expressed gene lists within each platform. Cumulatively, these comparisons indicate that data quality is essentially equivalent between the one- and two-color approaches and strongly suggest that this variable need not be a primary factor in decisions regarding experimental microarray design. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cogenics, Morrisville, NC 27560 USA. Agilent Technol, Integrated Biol Solut, Santa Clara, CA 95052 USA. SAS Inst Inc, Cary, NC 27513 USA. US FDA, Natl Ctr Toxicol Res, ZTech Corp, Jefferson, AR 72079 USA. NCI, Adv Technol Ctr, Bethesda, MD 20892 USA. Yale Univ, WM Keck Biotechnol Resource Lab, New Haven, CT 06511 USA. Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27101 USA. CapitalBio Corp, Beijing 102206, Peoples R China. EAT, Gene Express Chips, B-5000 Namur, Belgium. RP Patterson, TA (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tucker.patterson@fda.hhs.gov NR 24 TC 322 Z9 360 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1140 EP 1150 DI 10.1038/nbt1242 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200035 PM 16964228 ER PT J AU Shi, LM Reid, LH Jones, WD Shippy, R Warrington, JA Baker, SC Collins, PJ de Longueville, F Kawasaki, ES Lee, KY Luo, YL Sun, YMA Willey, JC Setterquist, RA Fischer, GM Tong, WD Dragan, YP Dix, DJ Frueh, FW Goodsaid, FM Herman, D Jensen, RV Johnson, CD Lobenhofer, EK Puri, RK Scherf, U Thierry-Mieg, J Wang, C Wilson, M Wolber, PK Zhang, L Amur, S Bao, WJ Barbacioru, CC Lucas, AB Bertholet, V Boysen, C Bromley, B Brown, D Brunner, A Canales, R Cao, XXM Cebula, TA Chen, JJ Cheng, J Chu, TM Chudin, E Corson, J Corton, JC Croner, LJ Davies, C Davison, TS Delenstarr, G Deng, XT Dorris, D Eklund, AC Fan, XH Fang, H Fulmer-Smentek, S Fuscoe, JC Gallagher, K Ge, WG Guo, L Guo, X Hager, J Haje, PK Han, J Han, T Harbottle, HC Harris, SC Hatchwell, E Hauser, CA Hester, S Hong, HX Hurban, P Jackson, SA Ji, HL Knight, CR Kuo, WP LeClerc, JE Levy, S Li, QZ Liu, CM Liu, Y Lombardi, MJ Ma, YQ Magnuson, SR Maqsodi, B McDaniel, T Mei, N Myklebost, O Ning, BT Novoradovskaya, N Orr, MS Osborn, TW Papallo, A Patterson, TA Perkins, RG Peters, EH Peterson, R Philips, KL Pine, PS Pusztai, L Qian, F Ren, HZ Rosen, M Rosenzweig, BA Samaha, RR Schena, M Schroth, GP Shchegrova, S Smith, DD Staedtler, F Su, ZQ Sun, HM Szallasi, Z Tezak, Z Thierry-Mieg, D Thompson, KL Tikhonova, I Turpaz, Y Vallanat, B Van, C Walker, SJ Wang, SJ Wang, YH Wolfinger, R Wong, A Wu, J Xiao, CL Xie, Q Xu, J Yang, W Zhang, L Zhong, S Zong, YP Slikker, W AF Shi, Leming Reid, Laura H. Jones, Wendell D. Shippy, Richard Warrington, Janet A. Baker, Shawn C. Collins, Patrick J. de Longueville, Francoise Kawasaki, Ernest S. Lee, Kathleen Y. Luo, Yuling Sun, Yongming Andrew Willey, James C. Setterquist, Robert A. Fischer, Gavin M. Tong, Weida Dragan, Yvonne P. Dix, David J. Frueh, Felix W. Goodsaid, Federico M. Herman, Damir Jensen, Roderick V. Johnson, Charles D. Lobenhofer, Edward K. Puri, Raj K. Scherf, Uwe Thierry-Mieg, Jean Wang, Charles Wilson, Mike Wolber, Paul K. Zhang, Lu Amur, Shashi Bao, Wenjun Barbacioru, Catalin C. Lucas, Anne Bergstrom Bertholet, Vincent Boysen, Cecilie Bromley, Bud Brown, Donna Brunner, Alan Canales, Roger Cao, Xiaoxi Megan Cebula, Thomas A. Chen, James J. Cheng, Jing Chu, Tzu-Ming Chudin, Eugene Corson, John Corton, J. Christopher Croner, Lisa J. Davies, Christopher Davison, Timothy S. Delenstarr, Glenda Deng, Xutao Dorris, David Eklund, Aron C. Fan, Xiao-hui Fang, Hong Fulmer-Smentek, Stephanie Fuscoe, James C. Gallagher, Kathryn Ge, Weigong Guo, Lei Guo, Xu Hager, Janet Haje, Paul K. Han, Jing Han, Tao Harbottle, Heather C. Harris, Stephen C. Hatchwell, Eli Hauser, Craig A. Hester, Susan Hong, Huixiao Hurban, Patrick Jackson, Scott A. Ji, Hanlee Knight, Charles R. Kuo, Winston P. LeClerc, J. Eugene Levy, Shawn Li, Quan-Zhen Liu, Chunmei Liu, Ying Lombardi, Michael J. Ma, Yunqing Magnuson, Scott R. Maqsodi, Botoul McDaniel, Tim Mei, Nan Myklebost, Ola Ning, Baitang Novoradovskaya, Natalia Orr, Michael S. Osborn, Terry W. Papallo, Adam Patterson, Tucker A. Perkins, Roger G. Peters, Elizabeth H. Peterson, Ron Philips, Kenneth L. Pine, P. Scott Pusztai, Lajos Qian, Feng Ren, Hongzu Rosen, Mitch Rosenzweig, Barry A. Samaha, Raymond R. Schena, Mark Schroth, Gary P. Shchegrova, Svetlana Smith, Dave D. Staedtler, Frank Su, Zhenqiang Sun, Hongmei Szallasi, Zoltan Tezak, Zivana Thierry-Mieg, Danielle Thompson, Karol L. Tikhonova, Irina Turpaz, Yaron Vallanat, Beena Van, Christophe Walker, Stephen J. Wang, Sue Jane Wang, Yonghong Wolfinger, Russ Wong, Alex Wu, Jie Xiao, Chunlin Xie, Qian Xu, Jun Yang, Wen Zhang, Liang Zhong, Sheng Zong, Yaping Slikker, William, Jr. CA MAQC Consortium TI The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements SO NATURE BIOTECHNOLOGY LA English DT Article ID EXTERNAL RNA CONTROLS; PLATFORM CONSISTENCY; PERFORMANCE; CANCER; COMPARABILITY; GENOMICS AB Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Express Anal Inc, Durham, NC 27713 USA. GE Healthcare, Tempe, AZ 85284 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Illuminia Inc, San Diego, CA 92121 USA. Agilent Technol, Santa Clara, CA 95051 USA. Eppendorf Array Technol, B-5000 Namur, Belgium. NCI, Ctr Adv Technol, Bethesda, MD 20892 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. Panomics Inc, Fremont, CA 94555 USA. Med Univ Ohio, Toledo, OH 43614 USA. Ambion, Austin, TX 78744 USA. Stratagene Corp, La Jolla, CA 92130 USA. US EPA, Off Res & Dev, Res Triangle Pk, NC 27711 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ Massachusetts, Boston, MA 02125 USA. Asuragen Inc, Austin, TX 78744 USA. Cogenics, Morrisville, NC 27560 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Los Angeles, CA 90048 USA. Solexa Inc, Hayward, CA 94545 USA. SAS Inst Inc, Cary, NC 27513 USA. ViaLogy Corp, Altadena, CA 91001 USA. Operon Biotechnol, Huntsville, AL 35805 USA. Z Tech Corp, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. CapitalBio Corp, Beijing 102206, Peoples R China. Biogen Idec Inc, San Diego, CA 92122 USA. US EPA, Off Sci Advisor, Washington, DC 20460 USA. Yale Univ, WM Keck Biotechnol Resource Lab, New Haven, CT 06511 USA. TeleChem Arraylt, Sunnyvale, CA 94089 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Cold Spring Harbor Lab, Woodbury, NY 11797 USA. Burnham Inst, La Jolla, CA 92037 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Gene Express Inc, Toledo, OH 43614 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Vanderbilt Univ, Nashville, TN 37232 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Univ Texas, Dept Comp Sci, Richardson, TX 75083 USA. GenUs BioSyst Inc, Northbrook, IL 60062 USA. Natl Hosp Norway, Radium Hosp Hlth Ctr, Norwegian Microarray Consortium, N-0310 Oslo, Norway. Novartis, Cambridge, MA 02139 USA. MD Anderson Canc Ctr, Breast Med Oncol Dept, Unit 1354, Houston, TX 77230 USA. Luminex Corp, Austin, TX 78727 USA. Harvard Univ, Sch Med, Childrens Hosp, Informat Program,Harvard MIT Div Hlth Sci & Tech, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. Full Moon Biosyst Inc, Sunnyvale, CA 94085 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov RI Guo, Lei/E-9232-2011; Myklebost, Ola/E-9335-2010; mei, nan/E-8915-2011; Su, Zhenqiang/H-3914-2012; THIERRY-MIEG, Jean/F-1975-2017; OI Johnson, Charles/0000-0003-3892-7082; Myklebost, Ola/0000-0002-2866-3223; mei, nan/0000-0002-3501-9014; THIERRY-MIEG, Jean/0000-0002-0396-6789; Szallasi, Zoltan/0000-0001-5395-7509; Eklund, Aron Charles/0000-0003-0861-1001; Croner, Lisa/0000-0002-3921-1484 FU Intramural NIH HHS [Z99 LM999999] NR 41 TC 1187 Z9 1242 U1 7 U2 84 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1151 EP 1161 DI 10.1038/nbt1239 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200036 PM 16964229 ER PT J AU Guo, L Lobenhofer, EK Wang, C Shippy, R Harris, SC Zhang, L Mei, N Chen, T Herman, D Goodsaid, FM Hurban, P Phillips, KL Xu, J Deng, XT Sun, YMA Tong, WD Dragan, YP Shi, LM AF Guo, Lei Lobenhofer, Edward K. Wang, Charles Shippy, Richard Harris, Stephen C. Zhang, Lu Mei, Nan Chen, Tao Herman, Damir Goodsaid, Federico M. Hurban, Patrick Phillips, Kenneth L. Xu, Jun Deng, Xutao Sun, Yongming Andrew Tong, Weida Dragan, Yvonne P. Shi, Leming TI Rat toxicogenomic study reveals analytical consistency across microarray platforms SO NATURE BIOTECHNOLOGY LA English DT Article ID PYRROLIZIDINE SENECIO ALKALOIDS; BIG BLUE RATS; GENE-EXPRESSION; ARISTOLOCHIC ACID; VITAMIN-A; COPPER; METABOLISM; LIVER; MUTAGENICITY; RIDDELLIINE AB To validate and extend the findings of the MicroArray Quality Control (MAQC) project, a biologically relevant toxicogenomics data set was generated using 36 RNA samples from rats treated with three chemicals (aristolochic acid, riddelliine and comfrey) and each sample was hybridized to four microarray platforms. The MAQC project assessed concordance in intersite and cross-platform comparisons and the impact of gene selection methods on the reproducibility of profiling data in terms of differentially expressed genes using distinct reference RNA samples. The real-world toxicogenomic data set reported here showed high concordance in intersite and cross-platform comparisons. Further, gene lists generated by fold-change ranking were more reproducible than those obtained by t-test P value or Significance Analysis of Microarrays. Finally, gene lists generated by fold-change ranking with a nonstringent P-value cutoff showed increased consistency in Gene Ontology terms and pathways, and hence the biological impact of chemical exposure could be reliably deduced from all platforms analyzed. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cogenics, Div Clin Data A, Morrisville, NC 27560 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, David Geffen Sch Med, Transcript Genom Core, Los Angeles, CA 90048 USA. GE Healthcare, Tempe, AZ 85284 USA. Solexa, Hayward, CA 94545 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Appl Biosyst Inc, Foster City, CA 94404 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov; leming.shi@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 30 TC 272 Z9 287 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2006 VL 24 IS 9 BP 1162 EP 1169 DI 10.1038/nbt1238 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 083YK UT WOS:000240495200037 PM 17061323 ER PT J AU Wang, CG Chen, LH Hou, XH Li, ZY Kabra, N Ma, YH Nemoto, S Finkel, T Gu, W Cress, WD Chen, JD AF Wang, Chuangui Chen, Lihong Hou, Xinghua Li, Zhenyu Kabra, Neha Ma, Yihong Nemoto, Shino Finkel, Toren Gu, Wei Cress, W. Douglas Chen, Jiandong TI Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage SO NATURE CELL BIOLOGY LA English DT Article ID LIFE-SPAN EXTENSION; CELL-SURVIVAL; SACCHAROMYCES-CEREVISIAE; CALORIE RESTRICTION; P53; TRANSCRIPTION; DEACETYLASE; EXPRESSION; INDUCTION; CYCLE AB The nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 (silent information regulator 2) regulates gene silencing in yeast and promotes lifespan extension during caloric restriction. The mammalian homologue of Sir2 (SirT1) regulates p53, NF-kappa B and Forkhead transcription factors, and is implicated in stress response. This report shows that the cell-cycle and apoptosis regulator E2F1 induces SirT1 expression at the transcriptional level. Furthermore, SirT1 binds to E2F1 and inhibits E2F1 activities, forming a negative feedback loop. Knockdown of SirT1 by small interference RNA (siRNA) increases E2F1 transcriptional and apoptotic functions. DNA damage by etoposide causes E2F1-dependent induction of SirT1 expression and knockdown of SirT1 increases sensitivity to etoposide. These results reveal a mutual regulation between E2F1 and SirT1 that affects cellular sensitivity to DNA damage. C1 H Lee Moffit Canc Ctr & Res Inst, Mol Oncol Program, Tampa, FL 33612 USA. Columbia Univ, Coll Phys & Surg, Inst Canc Genet, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. RP Chen, JD (reprint author), H Lee Moffit Canc Ctr & Res Inst, Mol Oncol Program, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM jchen@moffitt.usf.edu NR 30 TC 234 Z9 255 U1 6 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2006 VL 8 IS 9 BP 1025 EP U109 DI 10.1038/ncb1468 PG 11 WC Cell Biology SC Cell Biology GA 080IS UT WOS:000240241700020 PM 16892051 ER PT J AU De Piccoli, G Cortes-Ledesma, F Ira, G Torres-Rosell, J Uhle, S Farmer, S Hwang, JY Machin, F Ceschia, A McAleenan, A Cordon-Preciado, V Clemente-Blanco, A Vilella-Mitjana, F Ullal, P Jarmuz, A Leitao, B Bressan, D Dotiwala, F Papusha, A Zhao, XL Myung, K Haber, JE Aguilera, A Aragon, L AF De Piccoli, Giacomo Cortes-Ledesma, Felipe Ira, Gregory Torres-Rosell, Jordi Uhle, Stefan Farmer, Sarah Hwang, Ji-Young Machin, Felix Ceschia, Audrey McAleenan, Alexandra Cordon-Preciado, Violeta Clemente-Blanco, Andres Vilella-Mitjana, Felip Ullal, Pranav Jarmuz, Adam Leitao, Beatriz Bressan, Debra Dotiwala, Farokh Papusha, Alma Zhao, Xiaolan Myung, Kyungjae Haber, James E. Aguilera, Andres Aragon, Luis TI Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination SO NATURE CELL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; YEAST; COHESIN; REGIONS; GENES AB DNA double-strand breaks (DSB) can arise during DNA replication, or after exposure to DNA-damaging agents, and their correct repair is fundamental for cell survival and genomic stability. Here, we show that the Smc5-Smc6 complex is recruited to DSBs de novo to support their repair by homologous recombination between sister chromatids. In addition, we demonstrate that Smc5-Smc6 is necessary to suppress gross chromosomal rearrangements. Our findings show that the Smc5-Smc6 complex is essential for genome stability as it promotes repair of DSBs by error-free sisterchromatid recombination (SCR), thereby suppressing inappropriate non-sister recombination events. C1 Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Cell Cycle Grp, London W12 0NN, England. Univ Sevilla, Fac Biol, Dept Genet, E-41012 Seville, Spain. Brandeis Univ, Rosenstiel Ctr, Waltham, MA 02454 USA. Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA. Natl Human Genome Res Inst, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10021 USA. RP Haber, JE (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Cell Cycle Grp, Du Cane Rd, London W12 0NN, England. EM haber@brandeis.edu; aguilo@us.es; luis.aragon@csc.mrc.ac.uk RI Ira, Grzegorz/B-7912-2010; Torres-Rosell, Jordi/A-4213-2010; Dotiwala, Farokh/C-7068-2009; Clemente Blanco, Andres/D-4255-2014; Cortes Ledesma, Felipe/F-4803-2014; OI Torres-Rosell, Jordi/0000-0003-1308-6926; Clemente Blanco, Andres/0000-0002-3674-0671; Cortes Ledesma, Felipe/0000-0002-0440-6783; Zhao, Xiaolan/0000-0002-8302-6905; Hwang, Ji-Young/0000-0001-8044-1989; Haber, James/0000-0002-1878-0610; Aguilera, Andres/0000-0003-4782-1714 FU Medical Research Council [MC_U120074328]; NIGMS NIH HHS [GM20056, R01 GM020056, R01 GM080600, R01 GM080670, R37 GM020056] NR 18 TC 104 Z9 104 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2006 VL 8 IS 9 BP 1032 EP U118 DI 10.1038/ncb1466 PG 12 WC Cell Biology SC Cell Biology GA 080IS UT WOS:000240241700021 PM 16892052 ER PT J AU Shiva, S Wang, X Ringwood, LA Xu, XY Yuditskaya, S Annavajjhala, V Miyajima, H Hogg, N Harris, ZL Gladwin, MT AF Shiva, Sruti Wang, Xunde Ringwood, Lorna A. Xu, Xueying Yuditskaya, Susan Annavajjhala, Vidhya Miyajima, Hiroaki Hogg, Neil Harris, Zena Leah Gladwin, Mark T. TI Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis SO NATURE CHEMICAL BIOLOGY LA English DT Article ID IN-VIVO; LIPID-PEROXIDATION; NITROSOTHIOL FORMATION; ISCHEMIA-REPERFUSION; SERUM CERULOPLASMIN; VASCULAR CONTROL; GENE-EXPRESSION; S-NITROSOTHIOLS; FATTY-ACIDS; ACERULOPLASMINEMIA AB Nitrite represents a bioactive reservoir of nitric oxide ( NO) that may modulate vasodilation, respiration and cytoprotection after ischemia-reperfusion injury. Although nitrite formation is thought to occur via reaction of NO with oxygen, this third-order reaction cannot compete kinetically with the reaction of NO with hemoglobin to form nitrate. Indeed, the formation of nitrite from NO in the blood is limited when plasma is substituted with physiological buffers, which suggests that plasma contains metal-based enzymatic pathways for nitrite synthesis. We therefore hypothesized that the multicopper oxidase, ceruloplasmin, could oxidize NO to NO+, with subsequent hydration to nitrite. Accordingly, plasma NO oxidase activity was decreased after ceruloplasmin immunodepletion, in ceruloplasmin knockout mice and in people with congenital aceruloplasminemia. Compared to controls, plasma nitrite concentrations were substantially reduced in ceruloplasmin knockout mice, which were more susceptible to liver infarction after ischemia and reperfusion. The extent of hepatocellular infarction normalized after nitrite repletion. These data suggest new functions for the multicopper oxidases in endocrine NO homeostasis and nitrite synthesis, and they support the hypothesis that physiological concentrations of nitrite contribute to hypoxic signaling and cytoprotection. C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Dept Anaesthesia & Crit Care Med, Baltimore, MD 21287 USA. Sch Med, Baltimore, MD 21287 USA. Hamamatsu Univ Sch Med, Dept Med 1, Hamamatsu, Shizuoka 4313192, Japan. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 52 TC 192 Z9 202 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD SEP PY 2006 VL 2 IS 9 BP 486 EP 493 DI 10.1038/nchembio813 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 075XO UT WOS:000239920900012 PM 16906150 ER PT J AU Hawk, ET Viner, JL AF Hawk, Ernest T. Viner, Jaye L. TI Do statins prevent cancer? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE cancer; HMG-CoA reductase inhibitor; incidence; statin; survival ID RISK; PRAVASTATIN; TRIALS C1 NCI, Off Ctr Training & Resources, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, Off Ctr Training & Resources, Suite 700,6116 Execut Blvd, Bethesda, MD 20892 USA. EM hawke@mail.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD SEP PY 2006 VL 3 IS 9 BP 478 EP 479 DI 10.1038/ncponc0586 PG 2 WC Oncology SC Oncology GA 079TJ UT WOS:000240200500006 PM 16955084 ER PT J AU Mittleman, BB Lipsky, PE AF Mittleman, Barbara B. Lipsky, Peter E. TI Patient-centered outcomes: a bridge too far? SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Editorial Material C1 NIH, Off Sci Policy, Program Publ Private Partnerships, Bethesda, MD 20892 USA. RP Mittleman, BB (reprint author), NIH, Off Sci Policy, Program Publ Private Partnerships, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD SEP PY 2006 VL 2 IS 9 BP 457 EP 457 DI 10.1038/ncprheum0289 PG 1 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 079TI UT WOS:000240200400001 PM 16951695 ER PT J AU Hu, KP Nan, XS Bird, A Wang, WD AF Hu, Keping Nan, Xinsheng Bird, Adrian Wang, Weidong TI Testing for association between MeCP2 and the brahma-associated SWI/SNF chromatin-remodeling complex SO NATURE GENETICS LA English DT Letter C1 NIA, Genet Lab, NIH, Triad Technol Ctr, Baltimore, MD 21224 USA. Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Hu, KP (reprint author), NIA, Genet Lab, NIH, Triad Technol Ctr, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov NR 10 TC 23 Z9 25 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2006 VL 38 IS 9 BP 962 EP 964 DI 10.1038/ng0906-962 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 078OC UT WOS:000240112100003 PM 16940996 ER PT J AU Ghosh, MC Ollivierre-Wilson, H Cooperman, S Rouault, TA AF Ghosh, Manik C. Ollivierre-Wilson, Hayden Cooperman, Sharon Rouault, Tracey A. TI Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse - Reply SO NATURE GENETICS LA English DT Letter ID TARGETED DELETION; MICE; METABOLISM C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ghosh, MC (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM trou@helix.nih.gov NR 10 TC 9 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2006 VL 38 IS 9 BP 969 EP 970 DI 10.1038/ng0906-969 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 078OC UT WOS:000240112100006 ER PT J AU Stumhofer, JS Laurence, A Wilson, EH Huang, E Tato, CM Johnson, LM Villarino, AV Huang, QL Yoshimura, A Sehy, D Saris, CJM O'Shea, JJ Hennighausen, L Ernst, M Hunter, CA AF Stumhofer, Jason S. Laurence, Arian Wilson, Emma H. Huang, Elaine Tato, Cristina M. Johnson, Leanne M. Villarino, Alejandro V. Huang, Qiulong Yoshimura, Akihiko Sehy, David Saris, Christiaan J. M. O'Shea, John J. Hennighausen, Lothar Ernst, Matthias Hunter, Christopher A. TI Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system SO NATURE IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; I CYTOKINE RECEPTOR; TOXOPLASMIC ENCEPHALITIS; KLEBSIELLA-PNEUMONIAE; JOINT INFLAMMATION; IL-2 PRODUCTION; DEFICIENT MICE; CUTTING EDGE; BONE EROSION; IFN-GAMMA AB Studies have focused on the events that influence the development of interleukin 17 (IL-17)-producing T helper cells (T-H-17 cells) associated with autoimmunity, such as experimental autoimmune encephalitis, but relatively little is known about the cytokines that antagonize T-H-17 cell effector responses. Here we show that IL-27 receptor-deficient mice chronically infected with Toxoplasma gondii developed severe neuroinflammation that was CD4(+) T cell dependent and was associated with a prominent IL-17 response. In vitro, treatment of naive primary T cells with IL-27 suppressed the development T-H-17 cells induced by IL-6 and transforming growth factor-beta, which was dependent on the intracellular signaling molecule STAT1 but was independent of inhibition of IL-6 signaling mediated by the suppressor protein SOCS3. Thus IL-27, a potent inhibitor of T-H-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells. C1 Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. eBiosci, New Technol Dept, San Diego, CA 92121 USA. Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Fukuoka 8128582, Japan. Amgen Corp, Dept Inflammat Res, Newbury Pk, CA 91320 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, Melbourne, Vic 3050, Australia. RP Hunter, CA (reprint author), Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. EM chunter@vet.upenn.edu RI Laurence, Arian/A-8770-2009; Hunter, Christopher/H-1970-2011; Ernst, Matthias/D-5111-2012; Yoshimura, Akihiko/K-5515-2013; OI Laurence, Arian/0000-0003-0942-8292; Villarino, Alejandro/0000-0001-8068-2176 FU NIAID NIH HHS [1-T32-AI-055428, AI41158, AI42334, R01 AI041158]; NINDS NIH HHS [R01 NS072298] NR 60 TC 570 Z9 624 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2006 VL 7 IS 9 BP 937 EP 945 DI 10.1038/ni1376 PG 9 WC Immunology SC Immunology GA 076FL UT WOS:000239942300012 PM 16906166 ER PT J AU Kinjo, Y Tupin, E Wu, D Fujio, M Garcia-Navarro, R Benhnia, MREI Zajonc, DM Ben-Menachem, G Ainge, GD Painter, GF Khurana, A Hoebe, K Behar, SM Beutler, B Wilson, IA Tsuji, M Sellati, TJ Wong, CH Kronenberg, M AF Kinjo, Yuki Tupin, Emmanuel Wu, Douglass Fujio, Masakazu Garcia-Navarro, Raquel Benhnia, Mohammed Rafii-El-Idrissi Zajonc, Dirk M. Ben-Menachem, Gil Ainge, Gary D. Painter, Gavin F. Khurana, Archana Hoebe, Kasper Behar, Samuel M. Beutler, Bruce Wilson, Ian A. Tsuji, Moriya Sellati, Timothy J. Wong, Chi-Huey Kronenberg, Mitchell TI Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria SO NATURE IMMUNOLOGY LA English DT Article ID BORRELIA-BURGDORFERI; NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; CHOLESTERYL GALACTOSIDE; CRYSTAL-STRUCTURE; CD1D TETRAMERS; IDENTIFICATION; GLYCOSPHINGOLIPIDS; ACTIVATION; INFECTION AB Natural killer T ( NKT) cells recognize glycosphingolipids presented by CD1d molecules and have been linked to defense against microbial infections. Previously defined foreign glycosphingolipids recognized by NKT cells are uniquely found in nonpathogenic sphingomonas bacteria. Here we show that mouse and human NKT cells also recognized glycolipids, specifically a diacylglycerol, from Borrelia burgdorferi, which causes Lyme disease. The B. burgdorferi-derived, glycolipid- induced NKT cell proliferation and cytokine production and the antigenic potency of this glycolipid was dependent on acyl chain length and saturation. These data indicate that NKT cells recognize categories of glycolipids beyond those in sphingomonas and suggest that NKT cell responses driven by T cell receptor-mediated glycolipid recognition may provide protection against diverse pathogens. C1 La Jolla Inst Allergy & Immunol, Div Dev Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, HIV & Malaria Vaccine Program, New York, NY 10016 USA. Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA. Scripps Res Inst, Dept Biol Mol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. Gracefield Res Ctr, Carbohydrate Chem Team, Lower Hutt 6008, New Zealand. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kronenberg, M (reprint author), La Jolla Inst Allergy & Immunol, Div Dev Immunol, La Jolla, CA 92037 USA. EM mitch@liai.org RI Tsuji, Moriya/B-1471-2008; rafii el idrissi benhnia, mohammed/F-3019-2015; OI rafii el idrissi benhnia, mohammed/0000-0001-7405-9476; Hoebe, Kasper/0000-0002-3626-8098; Tsuji, Moriya/0000-0001-8587-277X; Behar, Samuel/0000-0002-3374-6699 FU NCI NIH HHS [CA58896]; NIAID NIH HHS [R01 AI054546, R37 AI071922, AI054546, AI45053, AI71922, AI062842]; NIGMS NIH HHS [GM44154, GM62116] NR 50 TC 399 Z9 411 U1 3 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2006 VL 7 IS 9 BP 978 EP 986 DI 10.1038/ni1380 PG 9 WC Immunology SC Immunology GA 076FL UT WOS:000239942300017 PM 16921381 ER PT J AU Rivera, J AF Rivera, Juan TI Snake bites and bee stings: the mast cell strikes back SO NATURE MEDICINE LA English DT Editorial Material ID MODEL AB Mast cells are thought to contribute to anaphylaxis and damage after snake bites and bee stings. But it now seems that these cells instead mount a defense against venom and inactivate toxins. C1 Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), Natl Inst Arthritis & Musculoskeletal & Skin Dis, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM juan_rivera@nih.gov NR 12 TC 11 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2006 VL 12 IS 9 BP 999 EP 1000 DI 10.1038/nm0906-999 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 082GE UT WOS:000240373900014 PM 16960571 ER PT J AU Wunder, C Churin, Y Winau, F Warnecke, D Vieth, M Lindner, B Zahringer, U Mollenkopf, HJ Heinz, E Meyer, TF AF Wunder, Christian Churin, Yuri Winau, Florian Warnecke, Dirk Vieth, Michael Lindner, Buko Zaehringer, Ulrich Mollenkopf, Hans-Joachim Heinz, Ernst Meyer, Thomas F. TI Cholesterol glucosylation promotes immune evasion by Helicobacter pylori SO NATURE MEDICINE LA English DT Article ID CAG PATHOGENICITY ISLAND; LIPID RAFTS; STEROL BIOSYNTHESIS; INFECTION; PROFILES; PROTEIN; PHAGOCYTOSIS; MACROPHAGES; GLUCOSIDES; MEMBRANES AB Helicobacter pylori infection causes gastric pathology such as ulcer and carcinoma. Because H. pylori is auxotrophic for cholesterol, we have explored the assimilation of cholesterol by H. pylori in infection. Here we show that H. pylori follows a cholesterol gradient and extracts the lipid from plasma membranes of epithelial cells for subsequent glucosylation. Excessive cholesterol promotes phagocytosis of H. pylori by antigen-presenting cells, such as macrophages and dendritic cells, and enhances antigen-specific T cell responses. A cholesterol-rich diet during bacterial challenge leads to T cell-dependent reduction of the H. pylori burden in the stomach. Intrinsic alpha-glucosylation of cholesterol abrogates phagocytosis of H. pylori and subsequent T cell activation. We identify the gene hp0421 as encoding the enzyme cholesterol-alpha-glucosyltransferase responsible for cholesterol glucosylation. Generation of knockout mutants lacking hp0421 corroborates the importance of cholesteryl glucosides for escaping phagocytosis, T cell activation and bacterial clearance in vivo. Thus, we propose a mechanism regulating the host - pathogen interaction whereby glucosylation of a lipid tips the scales towards immune evasion or response. C1 Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany. Univ Hamburg, Biozentrum Klein Flottbeck, D-22609 Hamburg, Germany. Otto Von Guericke Univ, Inst Pathol, D-39120 Magdeburg, Germany. Leibniz Ctr Med & Biosci, Res Ctr Borstel, D-23845 Borstel, Germany. Max Planck Inst Infect Biol, Core Facil Microarray, D-10117 Berlin, Germany. Max Planck Inst Infect Biol, Dept Biol Mol, D-10117 Berlin, Germany. RP Wunder, C (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM wunderc@mail.nih.gov; meyer@mpiib-berlin.mpg.de RI Meyer, Thomas F./J-2485-2013; Lindner, Buko/G-9731-2014; OI Meyer, Thomas F./0000-0002-6120-8679; Wunder, Christian/0000-0001-9091-0080 NR 47 TC 127 Z9 128 U1 5 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2006 VL 12 IS 9 BP 1030 EP 1038 DI 10.1038/nm1480 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 082GE UT WOS:000240373900027 PM 16951684 ER PT J AU Gaszner, M Felsenfeld, G AF Gaszner, Miklos Felsenfeld, Gary TI Insulators: exploiting transcriptional and epigenetic mechanisms SO NATURE REVIEWS GENETICS LA English DT Review ID ENHANCER-BLOCKING ACTIVITY; GYPSY CHROMATIN INSULATOR; BETA-GLOBIN INSULATOR; WING MARGIN ENHANCER; DROSOPHILA-MELANOGASTER; SACCHAROMYCES-CEREVISIAE; CHROMOSOMAL DOMAINS; BOUNDARY-ELEMENT; X-INACTIVATION; PROMOTER COMMUNICATION AB Insulators are DNA sequence elements that prevent inappropriate interactions between adjacent chromatin domains. One type of insulator establishes domains that separate enhancers and promoters to block their interaction, whereas a second type creates a barrier against the spread of heterochromatin. Recent studies have provided important advances in our understanding of the modes of action of both types of insulator. These new insights also suggest that the mechanisms of action of both enhancer blockers and barriers might not be unique to these types of element, but instead are adaptations of other gene-regulatory mechanisms. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. EM garyf@intra.niddk.nih.gov NR 84 TC 389 Z9 399 U1 1 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD SEP PY 2006 VL 7 IS 9 BP 703 EP 713 DI 10.1038/nrg1925 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 076FH UT WOS:000239941900015 PM 16909129 ER PT J AU Houtman, JCD Yamaguchi, H Barda-Saad, M Braiman, A Bowden, B Appella, E Schuck, P Samelson, LE AF Houtman, Jon C. D. Yamaguchi, Hiroshi Barda-Saad, Mira Braiman, Alex Bowden, Brent Appella, Ettore Schuck, Peter Samelson, Lawrence E. TI Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-PROTEIN INTERACTIONS; TERMINAL SH3 DOMAIN; TYROSINE KINASE; EGF RECEPTOR; ACTIVATION; SEDIMENTATION; TRANSDUCTION; AFFINITY; RAS AB Receptor oligomerization is vital for activating intracellular signaling, in part by initiating events that recruit effector and adaptor proteins to sites of active signaling. Whether these distal molecules themselves oligomerize is not well appreciated. In this study, we examined the molecular interactions of the adaptor protein GRB2. In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL. Using biochemical and biophysical techniques in conjunction with confocal microscopy, we observed that the simultaneous association of GRB2, via its SH2 and SH3 domains, with multivalent ligands led to the oligomerization of these ligands, which affected signaling. These data suggest that multipoint binding of distal adaptor proteins mediates the formation of oligomeric signaling clusters vital for intracellular signaling. C1 NCI, Biol Cellulaire & Mol Lab, US Natl Inst Hlth, ORD OD, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, US Natl Inst Hlth, ORD OD, Bethesda, MD 20892 USA. NCI, Prot Biophys Resource, US Natl Inst Hlth, ORD OD,Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Biol Cellulaire & Mol Lab, US Natl Inst Hlth, ORD OD, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov RI Braiman, Alex/F-2179-2012; OI Braiman, Alex/0000-0003-2802-1148; Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS NR 39 TC 106 Z9 108 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD SEP PY 2006 VL 13 IS 9 BP 798 EP 805 DI 10.1038/nsbm1133 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 092MY UT WOS:000241102400015 PM 16906159 ER PT J AU Squarize, CH Castilho, RM Sriuranpong, V Pinto, DS Gutkind, JS AF Squarize, Cristiane H. Castilho, Rogerio M. Sriuranpong, Virote Pinto, Decio S., Jr. Gutkind, Jorge Silvio TI Molecular cross-talk between the NF kappa B and STAT3 signaling pathways in head and neck squamous cell carcinoma SO NEOPLASIA LA English DT Article DE oral cancer; IL-6; cytokine; gene expression regulation; transcription factor ID GROWTH-FACTOR RECEPTOR; CONSTITUTIVE ACTIVATION; CYTOKINE EXPRESSION; LIVER DEGENERATION; PROSTATE-CANCER; IN-VIVO; SURVIVAL; INTERLEUKIN-6; KINASE; PROLIFERATION AB The development of head and neck squamous cell carcinoma (HNSCC) involves the accumulation of genetic and epigenetic alterations in tumor-suppressor proteins, together with the persistent activation of growth-promoting signaling pathways. The activation of epidermal growth factor receptor (EGFR) is a frequent event in HNSCC. However, EGFR-independent mechanisms also contribute to the activation of key intracellular signaling routes, including signal transducer and activator of transcription- 3 (STAT3), nuclear factor kappa B (NF kappa B), and Akt. Indeed, the autocrine activation of the gp130 cytokine receptor in HNSCC cells by tumor-released cytokines, such as IL-6, can result in the EGFR-independent activation of STAT3. In this study, we explored the nature of the molecular mechanism underlying enhanced IL-6 secretion in HNSCC cells. We found that HNSCC cells display an increased activity of the IL-6 promoter, which is dependent on the presence of an intact NF kappa B site. Furthermore, NF kappa B inhibition downregulated IL-6 gene and protein expression, and decreased the release of multiple cytokines. Interestingly, interfering with NF kappa B function also prevented the autocrine/paracrine activation of STAT3 in HNSCC cells. These findings demonstrate a cross-talk between the NF kappa B and the STAT3 signaling systems, and support the emerging notion that HNSCC results from the aberrant activity of a signaling network. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Sch Dent, Dept Oral Pathol, Sao Paulo, Brazil. Chulalongkorn Univ, Dept Med, Med Oncol Unit, Bangkok, Thailand. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Castilho, Rogerio/E-4987-2010; Pinto, Decio/B-6041-2011 OI Pinto, Decio/0000-0001-6198-5155 NR 65 TC 97 Z9 100 U1 0 U2 3 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD SEP PY 2006 VL 8 IS 9 BP 733 EP 746 DI 10.1593/neo.06274 PG 14 WC Oncology SC Oncology GA 083MV UT WOS:000240460900006 PM 16984731 ER PT J AU Di Iorio, A Cherubini, A Volpato, S Sparvieri, E Lauretani, F Franceschi, C Senin, U Abate, G Paganelli, R Martin, A Andres-Lacueva, C Ferrucci, L AF Di Iorio, Angelo Cherubini, Antonio Volpato, Stefano Sparvieri, Eleonora Lauretani, Fulvio Franceschi, Claudio Senin, Umberto Abate, Giuseppe Paganelli, Roberto Martin, Antonio Andres-Lacueva, Cristina Ferrucci, Luigi TI Markers of inflammation, Vitamin E and peripheral nervous system function - The InCHIANTI study SO NEUROBIOLOGY OF AGING LA English DT Article DE inflammation; Vitamin E; peripheral nervous system; aging ID DIABETIC RATS; OXIDATIVE STRESS; ALPHA-TOCOPHEROL; WOMENS HEALTH; REGENERATION; CONDUCTION; BRAIN; AGE; SUPPLEMENTATION; ESTROGEN AB Background:: Aging of the peripheral nervous system is associated with several morphologic and functional changes, including a decrease of the nerve conduction velocity. There is evidence that these changes contribute to age-related-decline in muscle strength, sensory discrimination, and autonomic responses. The aim of this study was to characterize the decline in nerve conduction velocity in the peripheral nervous system over the aging process and to identify factors that, independent of age, affect nerve conduction velocity. Methods:: We measured motor nerve conduction velocity of the right superficial peroneal nerve using a standard neurophysiologic technique in a population-based sample of subjects aged between 20 and 103 years old enrolled in the InCHIANTI study. Results:: Average conduction velocities in the peripheral nerve decreased linearly with age in both sexes. We found that diabetes, cognitive impairment, uric acid, sIL-6R and alpha-tocopherol were significant predictors of nerve conduction velocity independently of the potential confounding effect of age, sex, sex x age interaction term, height, lymphocytes, neutrophils number, alpha 1 and alpha 2-globulin serum protein. Conclusions:: Our findings are consistent with the hypothesis that inflammation and inadequate antioxidant defenses are associated with accelerated decline of nerve conduction velocity over the aging process. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ G DAnnunzio, Dept Med & Sci Aging, Lab Clin Epidemiol, I-66013 Chieti, Italy. Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Tuscany Reg Hlth Agcy, Lab Clin Epidemiol, Florence, Italy. Univ Bologna, Dept Expt Pathol, Bologna, Italy. Univ G DAnnunzio, Dept Med & Sci Aging, Lab Immunol & Allergy, Chieti, Italy. Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Barcelona, Dept Nutr & Food Sci, CeRTA, Barcelona, Spain. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Di Iorio, A (reprint author), Univ G DAnnunzio, Med & Aging Geriatr Unit & Epidemiol, Via Vestini 5, I-66100 Chieti, Italy. EM a.diiorio@unich.it RI Andres-Lacueva, Cristina/J-3377-2012; VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016; OI Andres-Lacueva, Cristina/0000-0002-8494-4978; VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z99 AG999999]; NIMHD NIH HHS [263MD821336, 263MD916413, R01 MD009164] NR 34 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2006 VL 27 IS 9 BP 1280 EP 1288 DI 10.1016/j.neurobiolaging.2005.07.004 PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 073AB UT WOS:000239713400011 PM 16112778 ER PT J AU Li, TQ van Gelderen, P Merkle, H Talagala, L Koretsky, AP Duyn, J AF Li, Tie-Qiang van Gelderen, Peter Merkle, Hellmut Talagala, Lalith Koretsky, Alan P. Duyn, Jeff TI Extensive heterogeneity in white matter intensity in high-resolution T-2(*)-weighted MRI of the human brain at 7.0 T SO NEUROIMAGE LA English DT Article ID 8 TESLA; VASCULAR ANATOMY; CEREBRAL-CORTEX; OCCIPITAL LOBE; CONTRAST; SIGNAL; IRON; COIL; OXYGENATION; ARRAY AB MRI at high magnetic field strength potentially allows for an increase in resolution and image contrast. The gains are particularly dramatic for T-2(*)-weighted imaging, which is sensitive to susceptibility effects caused by a variety of sources, including deoxyhemoglobin, iron concentration, and tissue microstructure. On the other hand, the acquisition of high quality whole brain MRI at high field is hampered by the increased inhomogeneity in B-0 and B-1 fields. In this report, high-resolution gradient echo MRI was performed using an 8-channel detector to obtain T-2(*)-weighted images over large brain areas. The high SNR achieved with the multi-channel array enabled T-2(*)-weighted images of the brain with an unprecedented spatial resolution of up to 0.2 x 0.2 x 0.5 mm(3). This high resolution greatly facilitated the detection of microscopic susceptibility effects. In addition to the expected contrast between gray, white matter, cerebral spinal fluid, and veins, a large degree of heterogeneity in contrast was observed throughout the white matter of normal brain. The measured T-2(*) values in white matter varied as much as 30% with some of the variation apparently correlating with the presence of large fiber bundles. Published by Elsevier Inc. C1 Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Duyn, J (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Room 10-B1D724, Bethesda, MD 20892 USA. EM jhd@helix.nih.gov RI Duyn, Jozef/F-2483-2010; Koretsky, Alan/C-7940-2015; OI Koretsky, Alan/0000-0002-8085-4756; Li, Tieqiang/0000-0002-6636-8938; Li, Tie-Qiang/0000-0002-4866-5904 FU Intramural NIH HHS [Z01 NS002989-08] NR 38 TC 93 Z9 93 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2006 VL 32 IS 3 BP 1032 EP 1040 DI 10.1016/j.neuroimage.2006.05.053 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 083PI UT WOS:000240470300007 PM 16854600 ER PT J AU Shapiro, EM Gonzalez-Perez, O Garcia-Verdugo, JM Alvarez-Buylla, A Koretsky, AP AF Shapiro, Erik M. Gonzalez-Perez, Oscar Garcia-Verdugo, Jose Manuel Alvarez-Buylla, Arturo Koretsky, Alan P. TI Magnetic resonance imaging of the migration of neuronal precursors generated in the adult rodent brain SO NEUROIMAGE LA English DT Article DE MRI; iron oxide; stem cells; neurons; contrast agents ID NEURAL STEM-CELLS; IRON-OXIDE PARTICLES; IN-VIVO TRACKING; SUBVENTRICULAR ZONE; MAMMALIAN BRAIN; CHAIN MIGRATION; CELLULAR MRI; SINGLE CELLS; RAT; FOREBRAIN AB Neural progenitor cells (NPCs) reside within the subventricular zone (SVZ) in rodents. These NPCs give rise to neural precursors in adults that migrate to the olfactory bulb (OB) along a well-defined pathway, the rostral migratory stream (RMS). Here we demonstrate that these NPCs can be labeled, in vivo, in adult rats with fluorescent, micronsized iron oxide particles (MPIOs), and that magnetic resonance imaging (MRI) can detect migrating neural precursors carrying MPIOs along the RMS to the OB. Immunohistochemistry and electron microscopy indicated that particles were inside GFAP(+) neural progenitor cells in the SVZ, migrating PSA-NCAM(+) and Doublecortin(+) neural precursors within the RMS and OB, and Neu-N+ mature neurons in the OB. This work demonstrates that in vivo cell labeling of progenitor cells for MRI is possible and enables the serial, non-invasive visualization of endogenous progenitor/precursor cell migration. (c) 2006 Elsevier Inc. All rights reserved. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Radiol, Ctr Biomed Imaging, New York, NY 10016 USA. Univ Calif San Francisco, Dept Neurol Surg, Dev & Stem Cell Biol Program, San Francisco, CA 94143 USA. Univ Valencia, Inst Cavanilles, E-46100 Valencia, Spain. RP Shapiro, EM (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. EM erik.shapiro@yale.edu RI Gonzalez-Perez, Oscar/B-3680-2008; Koretsky, Alan/C-7940-2015; OI Gonzalez-Perez, Oscar/0000-0002-6527-485X; Koretsky, Alan/0000-0002-8085-4756; Garcia-Verdugo, Jose Manuel/0000-0001-9872-6499 FU Intramural NIH HHS [Z01 NS002989-08]; NINDS NIH HHS [R01 NS028478] NR 32 TC 111 Z9 121 U1 1 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2006 VL 32 IS 3 BP 1150 EP 1157 DI 10.1016/j.neuroimage.2006.04.219 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 083PI UT WOS:000240470300021 PM 16814567 ER PT J AU Yang, J Shen, J AF Yang, Jehoon Shen, Jun TI Increased oxygen consumption in the somatosensory cortex of alpha-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla SO NEUROIMAGE LA English DT Article DE focal activation; cerebral oxygen consumption rate; magnetic resonance spectroscopy ID HUMAN VISUAL-CORTEX; CEREBRAL-BLOOD-FLOW; MAGNETIC-RESONANCE-SPECTROSCOPY; CORTICAL GABA TURNOVER; IN-VIVO LACTATE; OXIDATIVE-METABOLISM; GLUCOSE CONSUMPTION; RELATIVE CMRO2; HUMAN BRAIN; C-13 NMR AB The significance of changes in cerebral oxygen consumption in focally activated brain tissue is still controversial. Since the rate of cerebral oxygen consumption is tightly coupled to that of tricarboxylic acid cycle which can be measured from the turnover kinetics of [4-C-13]glutamate using in vivo H-1{C-13} magnetic resonance spectroscopy, changes in tricarboxylic acid cycle flux rate were assessed in primary somatosensory cortex of a-chloralose anesthetized rats during electrical forepaw stimulation. With markedly improved H-1{C-13} magnetic resonance spectroscopy technique and the use of high magnetic field strength of 11.7 T accessible to the current study, [4-C-13]glutamate at 2.35 ppm was spectrally resolved from overlapping resonances of [4-C-13] glutamine at 2.46 ppm and [2-C-13]GABA at 2.28 ppm as well as the more distal [3-C-13]glutamate and [3-C-13]glutamine. The results showed a significantly increased V-TCA in focally activated primary somatosensory cortex during forepaw stimulation, corresponding to approximately 51 +/- 27% (n = 6, mean +/- SD) increase in cerebral oxygen consumption rate. Considering the high efficiency in producing adenosine triphosphate by oxidative metabolism of glucose, the results demonstrate that aerobic oxidative metabolism provides the majority of energy required for cerebral focal activation in a-chloralose anesthetized rats subjected to forepaw stimulation. (c) 2006 Elsevier Inc. All rights reserved. C1 NIMH, Mood & Anxiety Disorders Program, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mood & Anxiety Disorders Program, Mol Imaging Branch, Bldg 10 Rm,2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 52 TC 13 Z9 13 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2006 VL 32 IS 3 BP 1317 EP 1325 DI 10.1016/j.neuroimage.2006.05.010 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 083PI UT WOS:000240470300042 PM 16797191 ER PT J AU Doyon, WM Howard, EC Shippenberg, TS Gonzales, RA AF Doyon, William M. Howard, Elaina C. Shippenberg, Toni S. Gonzales, Rueben A. TI kappa-Opioid receptor modulation of accumbal dopamine concentration during operant ethanol self-administration SO NEUROPHARMACOLOGY LA English DT Article DE ethanol self-administration; operant; microdialysis; nucleus accumbens; nor-binaltorphimine ID VENTRAL TEGMENTAL AREA; RAT NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; NOR-BINALTORPHIMINE; REINFORCED BEHAVIOR; RHESUS-MONKEYS; ANTAGONISTS; ALCOHOL; RELEASE; AGONISTS AB Our study examined ethanol self-administration and accumbal dopamine concentration during K-opioid receptor (KOPr) blockade. Long-Evans rats were trained to respond for 20 min of access to 10% ethanol (with sucrose) over 7 days. Rats were injected s.c. with the long-acting KOPr antagonist, nor-binaltorphimine (NOR-BNI; 0 or 20 mg/kg) 15-20 h prior to testing. Microdialysis revealed a transient elevation in dopamine concentration within 5 min of ethanol access in controls. NOR-BNI-treated rats did not exhibit this response, but showed a latent increase in dopamine concentration at the end of the access period. The rise in dopamine levels correlated positively with dialysate ethanol concentration but not in controls. NOR-BNI did not alter dopamine levels in rats self-administering 10% sucrose. The transient dopamine response during ethanol acquisition in controls is consistent with previous results that were attributed to ethanol stimulus cues. The altered dopamine response to NOR-BNI during ethanol drinking suggests that KOPr blockade temporarily uncovered a pharmacological stimulation of dopamine release by ethanol. Despite these neurochemical changes, NOR-BNI did not alter operant responding or ethanol intake, suggesting that the KOPr is not involved in ethanol-reinforced behavior under the limited conditions we studied. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Texas, Coll Pharm, Div Pharmacol, Austin, TX 78712 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Natl Inst Drug Abuse, Intramural Res Program, Integrat Neurosci Sect, Behab Neurosci Branch, Baltimore, MD 21224 USA. RP Gonzales, RA (reprint author), Univ Texas, Coll Pharm, Div Pharmacol, 1 Univ Stn A1915, Austin, TX 78712 USA. EM rgonzales@mail.utexas.edu FU NIAAA NIH HHS [AA11852, 5F31AA014849-02, AA U01 13486-INIA, F31 AA014849, R01 AA011852, R37 AA011852, U01 AA013486] NR 46 TC 32 Z9 34 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2006 VL 51 IS 3 BP 487 EP 496 DI 10.1016/j.neuropharm.2006.04.005 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 088KZ UT WOS:000240811900009 PM 16781738 ER PT J AU Ide, S Minami, M Ishihara, K Uhl, GR Sora, I Ikeda, K AF Ide, Soichiro Minami, Masabumi Ishihara, Kumatoshi Uhl, George R. Sora, Ichiro Ikeda, Kazutaka TI Mu opioid receptor-dependent and independent components in effects of tramadol SO NEUROPHARMACOLOGY LA English DT Article DE opioid receptor; knockout mice; tramadol; antinociception; reward; adrenaline ID CONDITIONED PLACE PREFERENCE; MORPHINE-INDUCED ANALGESIA; KNOCKOUT MICE; ANTINOCICEPTIVE INTERACTION; RATS; PAIN; WITHDRAWAL; REWARD; GENE; BUPRENORPHINE AB Tramadol is thought to induce analgesia via both opioid and non-opioid pathways, although the precise mechanisms remain to be elucidated. In this study, we investigated the roles of the p-opioid receptor (MOP) in analgesic and rewarding effects of tramadol by using MOP knockout (KO) mice. Tramadol-induced antinociception, assessed by hot-plate and tail-flick tests, was significantly reduced in heterozygous and homozygous MOP-KO mice when compared with that in wild-type mice. Interestingly, however, tramadol retained its ability to induce significant antinociception in homozygous MOP-KO mice. The tramadol-induced antinociception remaining in homozygous MOP-KO mice was not significantly affected by methysergide, a serotonin receptor antagonist, but was partially blocked by yohimbine, an adrenaline alpha 2 receptor antagonist, and both naloxone, a non-selective opioid receptor antagonist, and yohimbine. In addition, antinociceptive effects of an active tramadol metabolite M1 were abolished or remarkably reduced in MOP-KO mice. On the other hand, neither wild-type nor homozygous MOP-KO mice showed significant place preference for tramadol in a conditioned place preference test, although there were slight tendencies toward preference in wild-type mice and avoidance in homozygous MOP-KO mice. These results strongly support the idea suggested in the previous pharmacological studies that MOP and the adrenaline alpha 2 receptor mediate most of the analgesic properties of tramadol. (c) 2006 Elsevier Ltd. All rights reserved. C1 Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, Tokyo 1568585, Japan. Hiroshima Int Univ, Fac Pharmaceut Sci, Neuropharmacol Lab, Kure 7370112, Japan. Hokkaido Univ, Dept Pharmacol, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan. NIDA, Baltimore, MD 21224 USA. Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 9808574, Japan. RP Ikeda, K (reprint author), Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM ikedak@prit.go.jp RI Ide, Soichiro/D-5472-2012; Minami, Masabumi/A-3883-2012; Ikeda, Kazutaka/I-4694-2013 OI Minami, Masabumi/0000-0002-0144-0679; Ikeda, Kazutaka/0000-0001-8342-0278 NR 34 TC 75 Z9 77 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2006 VL 51 IS 3 BP 651 EP 658 DI 10.1016/j.neuropharm.2006.05.008 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 088KZ UT WOS:000240811900026 PM 16793069 ER PT J AU Goldberg, TE Straub, RE Callicott, JH Hariri, A Mattay, VS Bigelow, L Coppola, R Egan, MF Weinberger, DR AF Goldberg, Terry E. Straub, Richard E. Callicott, Joseph H. Hariri, Ahmad Mattay, Venkata S. Bigelow, Llewellyn Coppola, Richard Egan, Michael F. Weinberger, Daniel R. TI The G72/G30 gene complex and cognitive abnormalities in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE G72; cognition; fMRI; gene; glutamate; schizophrenia ID BIPOLAR-AFFECTIVE-DISORDER; AMINO-ACID OXIDASE; WORKING-MEMORY; KETAMINE; BRAIN; RISK; ASSOCIATION; DISEASE; PATHOPHYSIOLOGY; SUSCEPTIBILITY AB A recently discovered gene complex, G72/G30 (hereafter G72, but now termed DAOA), was found to be associated with schizophrenia and with bipolar disorder, possibly because of an indirect effect on NMDA neurotransmission. In principle, if G72 increases risk for psychosis by this mechanism, it might impact with greater penetrance those cortically based cognitive and neurophysiological functions associated with NMDA signaling. We performed two independent family-based association studies (one sample contained more than 200 families and the other more than 65) of multiple SNPs in the G72 region and of multiple SNPs in the gene for (D)amino acid oxidase (DAAO), which may be modulated by G72. We examined the relationship between select cognitive measures in attention, working memory, and episodic memory and a restricted set of G72 SNPs in over 600 normal controls, schizophrenic patients, and their nonpsychotic siblings using mixed model ANOVAs. We also determined genotype effects on neurophysiology measures in normal controls using the fMRI BOLD response obtained during activation procedures involving either episodic memory or working memory. There were no significant single G72 SNP associations and clinical diagnosis in either sample, though one approached significance (p = 0.06). Diagnosis by genotype interaction effects for G72 SNP 10 were significant for cognitive variables assessing working memory and attention (p = 0.05), and at the trend level for episodic memory, such that in the schizophrenia group an exaggerated allele load effect in the predicted directions was observed. In the fMRI paradigms, a strong effect of G72 SNP 10 genotype was observed on BOLD activation in the hippocampus during the episodic memory paradigm. Tests of association with DAAO were consistently nonsignificant. We present evidence that SNP variations in the G72 gene region increase risk of cognitive impairment in schizophrenia. SNP variations were not strongly associated with clinical diagnosis in family-based analyses. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD USA. RP Goldberg, TE (reprint author), Hillside Hosp, Div Psychiat Res, 75 59 263rd St, Glen Oaks, NY 11004 USA. EM tgoldber@nshs.edu RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 NR 47 TC 95 Z9 96 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2006 VL 31 IS 9 BP 2022 EP 2032 DI 10.1038/sj.npp.1301049 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 075XJ UT WOS:000239920400019 PM 16554747 ER PT J AU Buchsbaum, MS Buchsbaum, BR Chokron, S Tang, C Wei, TC Byne, W AF Buchsbaum, Monte S. Buchsbaum, Bradley R. Chokron, Sylvie Tang, Cheuk Wei, Tse-Chung Byne, William TI Thalamocortical circuits: fMRI assessment of the pulvinar and medial dorsal nucleus in normal volunteers SO NEUROSCIENCE LETTERS LA English DT Article DE attention; blood oxygen level; cerebral blood flow; flanker task ID POSITRON-EMISSION-TOMOGRAPHY; ATTENTIONAL CONTROL; EFFECTIVE CONNECTIVITY; MEDIODORSAL NUCLEUS; GLUCOSE-METABOLISM; PREFRONTAL CORTEX; RHESUS-MONKEY; FRONTAL-LOBE; HUMAN BRAIN; SCHIZOPHRENIA AB This fMRI study investigates the activation of the thalamic nuclei in a spatial focusing-of-attention task previously shown to activate the pulvinar with FDG-PET and assesses the connectivity of the thalamic nuclei with cortical areas. Normal right-handed subjects (eight men, eight women, average age=32 years) viewed four types of stimuli positioned to the right or left of the central fixation point (left hemifield-large letter, left hemitield-small letter display with flanking letters; fight hemifield-large letter, fight hemifield-small letter display with flankers). BOLD responses to small letters surrounded by flankers were compared with responses to large isolated letters. To examine maximum functional regional connectivity, we modeled "subject" as a random effect and attained fixed effect parameter estimates and t-statistics for functional connectivity between each of the thalamic nuclei (pulvinar, medial dorsal, and anterior) as the seed region and each non-seed voxel. Greater BOLD activation for letters surrounded by flankers than for large letters was observed in the pulvinar as anticipated and was also marked in the medial dorsal nucleus (MDN), anterior and superior cingulate (BA24 and BA24' dorsolateral prefrontal cortex, and frontal operculum and insula. For the MDN, maximal functional connectivity was with the dorsolateral prefrontal cortex; correlations with left superior temporal, parietal, posterior frontal, and occipital regions were also observed. For the pulvinar, maximal functional connectivity was with parietal BA39; for anterior thalamus, with anterior cingulate. (c) 2006 Published by Elsevier Ireland Ltd. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. CNRS, Expt Psychol Lab, UMR 5105, Grenoble, France. Fdn Ophthalmol Rothschild, Neurol Serv, Paris, France. Mt Sinai Sch Med, Dept Radiol, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Buchsbaum, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. EM monte.buchsbaum@mssm.edu FU NIMH NIH HHS [MH-60023] NR 38 TC 29 Z9 29 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 1 PY 2006 VL 404 IS 3 BP 282 EP 287 DI 10.1016/j.neulet.2006.05.063 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 079GM UT WOS:000240163800008 PM 16860474 ER PT J AU Kutty, RK Samuel, W Chen, S Vijayasarathy, C Dun, Y Mysona, B Wiggert, B Smith, SB AF Kutty, R. Krishnan Samuel, William Chen, Shanyi Vijayasarathy, Camasamudram Dun, Ying Mysona, Barbara Wiggert, Barbara Smith, Sylvia B. TI Immunofluorescence analysis of the expression of Norpeg (Rai14) in retinal Muller and ganglion cells SO NEUROSCIENCE LETTERS LA English DT Article DE Rai14; Norpeg; retina; Muller cells; ganglion cells; immunofluorescence AB Novel retinal pigment epithelial cell gene (Norpeg, Rai14), a developmentally regulated mouse gene, encodes a protein containing six ankyrin repeats and a coiled-coil domain. The objective of the present study was to characterize the Norpeg protein and to analyze its expression in mouse retina using an antibody preparation that we developed. The similar to 110 kDa Norpeg was immunoprecipitated and characterized by mass spectrometry. Primary cultures of Miller and ganglion cells isolated from the mouse retina were found to express Norpeg when analyzed by immunoblotting and immunofluorescence microscopy. Immunofluorescence analysis of normal mouse retina sections demonstrated that Norpeg is expressed in cells of the ganglion cell layer, inner nuclear layer as well as in the retinal pigment epithelium. Immunoreactivity was also evident in the radial glial (Muller) cell fibers. Published by Elsevier Ireland Ltd. C1 NEI, Biochem Sect, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. RP Kutty, RK (reprint author), NEI, Biochem Sect, Lab Retinal Cell & Mol Biol, NIH, 7-329,7 Mem Dr, Bethesda, MD 20892 USA. EM kuttyk@nei.nih.gov FU Intramural NIH HHS NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 1 PY 2006 VL 404 IS 3 BP 294 EP 298 DI 10.1016/j.neulet.2006.06.006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 079GM UT WOS:000240163800010 PM 16806700 ER PT J AU Harry, GJ Lawler, C Brunssen, SH AF Harry, G. Jean Lawler, Cindy Brunssen, Susan H. TI Maternal infection and white matter toxicity SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE microglia; white matter damage; inflammation; oligodendrocyte ID CENTRAL-NERVOUS-SYSTEM; LOW-BIRTH-WEIGHT; AMNIOTIC-FLUID INTERLEUKIN-6; FETAL INFLAMMATORY RESPONSE; MESSENGER-RNA EXPRESSION; NEONATAL INTENSIVE-CARE; MULTIPLE BRAIN-REGIONS; NECROSIS-FACTOR-ALPHA; DOUBLE-STRANDED-RNA; PRETERM INFANTS AB Studies examining maternal infection as a risk factor for neurological disorders in the offspring have suggested that altered maternal immune status during pregnancy can be considered as an adverse event in prenatal development. Infection occurring in the mother during the gestational period has been implicated in multiple neurological effects. The current manuscript will consider the issue of immune/inflammatory conditions during prenatal development where adverse outcomes have been linked to maternal systemic infection. The discussions will focus primary on white matter and oligodendrocytes as they have been identified as target processes. This white matter damage occurs in very early preterm infants and in various other human diseases currently being examined for a linkage to maternal or early developmental immune status. The intent is to draw attention to the impact of altered immune status during pregnancy on the offspring for the consideration of such contributing factors to the general assessment of developmental neurotoxicology. C1 NIEHS, NIH, Neurotoxicol Grp, Lab Neurobiol ,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Div Extramural Res & Training, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Nursing, Chapel Hill, NC USA. Univ N Carolina, Neurodev Disorders Res Ctr, Chapel Hill, NC USA. RP Harry, GJ (reprint author), NIEHS, NIH, Neurotoxicol Grp, Lab Neurobiol ,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov FU NIEHS NIH HHS [Z01 ES021164-09] NR 192 TC 6 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 658 EP 670 DI 10.1016/j.neuro.2006.05.004 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800003 PM 16787664 ER PT J AU Li, GJ Choi, LS Wang, X Liu, J Waalkes, MP Zheng, W AF Li, G. Jane Choi, Lyung-Sun Wang, Xueqian Liu, Jie Waalkes, Michael P. Zheng, Wei TI Molecular mechanism of distorted iron regulation in the blood-CSF barrier and regional blood-brain barrier following in vivo subchronic manganese exposure SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE Manganese (Mn); Iron (Fe); brain-barrier system; Iron Regulatory Protein (IRP); Iron Responsive Element (IRE); Transferrin Receptor(TfR); oral administration; Choroid Plexus (CP); Blood-CSF Barrier (BCB); Blood-brain barrier; Ferritin (Ft) ID TRANSFERRIN RECEPTOR; PARKINSONS-DISEASE; CEREBROSPINAL-FLUID; GENE-EXPRESSION; H-FERRITIN; SUBUNIT; CELLS; RATS; OVEREXPRESSION; HOMEOSTASIS AB Previous studies in this laboratory indicated that manganese (Mn) exposure in vitro increases the expression of transferrin receptor (TfR) by enhancing the binding of iron regulatory proteins (IRPs) to iron responsive element-containing RNA. The current study further tested the hypothesis that in vivo exposure to Mn increased TfR expression at both blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (BCB), which contributes to altered iron (Fe) homeostasis in the CSF. Groups of rats (10-11 each) received oral gavages at doses of 5 mg Mn/kg or 15 mg Mn/kg as MnCl2 once daily for 30 days. Blood, CSF, and choroid plexus were collected and brain capillary fractions were separated from the regional parenchyma. Metal analyses showed that oral Mn exposure decreased concentrations of Fe in serum (-66%) but increased Fe in the CSF (+167%). Gel shift assay showed that Mn caused a dose-dependent increase of binding of IRP1 to iron responsive element-containing RNA in BCB in the choroid plexus (+70%), in regional BBB of capillaries of striatum (+39%), hippocampus (+56%), frontal cortex (+49%), and in brain parenchyma of striatum (+67%), hippocampus (+39%) and cerebellum (+28%). Real-time RT-PCR demonstrated that Mn exposure significantly increased the expression of TfR mRNA in choroid plexus and striatum with concomitant reduction in the expression of ferritin (Ft) mRNA. Collectively, these data indicate that in vivo Mn exposure results in Fe redistribution in body fluids through regulating the expression of TfR and ferritin at BCB and selected regional BBB. The disrupted Fe transport by brain barriers may underlie the distorted Fe homeostasis in the CSF. (C) 2006 Elsevier Inc. All rights reserved. C1 Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. NIEHS, NCI, Ctr Canc Res, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC 27709 USA. RP Zheng, W (reprint author), Purdue Univ, Sch Hlth Sci, 550 Stadium Mall Dr,CIVL 1163D, W Lafayette, IN 47907 USA. EM wzheng@purdue.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES 08146, R01 ES008146, R56 ES008146] NR 42 TC 22 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 737 EP 744 DI 10.1016/j.neuro.2006.02.003 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800011 PM 16545456 ER PT J AU Johnson, K Ryan, L Davis, J Elmore, A Guenther, B Marcus, J Maronpot, RR AF Johnson, Kennita Ryan, Linda Davis, Jeffrey Elmore, Amy Guenther, Brett Marcus, Jill Maronpot, Robert R. TI Application of magnetic resonance imaging in developmental neurotoxicity testing: A pilot study SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE MRI; methylazoxymethanol acetate (MAM); stereology ID PRENATAL EXPOSURE; BRAIN; METHYLAZOXYMETHANOL; NEUROPATHOLOGY; MICROSCOPY; MODEL; RAT AB In a pilot developmental neurotoxicity study, a protocol was designed to utilize three-dimensional magnetic resonance (MR) images for linear and volumetric measurements of the developing rat brain. MR imaging, because of its non-destructive nature, provides a complement to traditional optical microscopy. Sprague-Dawley dams received 0, 1.25, 4.0 or 7.5 mg/kg methylazoxy methanol acetate (MAM) by intraperitoneal injection during gestation days 13-15. At postnatal days (PND) 23 and 60, brains from representative male and female rats from two dams in each dose group were fixed with 10% neutral buffered formalin by transcardial perfusion for in situ MR imaging. A 7 T small animal magnet system was used to obtain isotropic images at 100 mu m resolution for PND 23 and 150 mu m resolution for PND 60. Data from a rapid screening method based on midpoint MR slices of whole brain, cerebrum, cerebellum, and hippocampus showed a dose-related decreased volume of whole brain, cerebrum, and hippocampus in treated rats. Subsequent volumetric estimates using the Cavalieri method confirmed these findings. The brains were subsequently removed and processed for conventional histologic examination of hematoxylin and eosin-stained sections. It is concluded that MR imaging in rat developmental neurotoxicity studies offers the advantages of in situ volumetric measurements of brain structures while preserving the samples for conventional optical microscopy. C1 NIEHS, NIH, DHHS, Lab Expt Pathol,RTP, Res Triangle Pk, NC 27709 USA. MRPath Inc, Durham, NC 27703 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. RP Johnson, K (reprint author), NIEHS, NIH, DHHS, Lab Expt Pathol,RTP, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM johnso58@niehs.nih.gov FU Intramural NIH HHS NR 15 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 846 EP 851 DI 10.1016/j.neuro.2006.06.005 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800023 PM 16860869 ER PT J AU Gohlke, M AF Gohlke, M. TI Computational tools for comparisons across stages of neurodevelopment. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res C1 NIEHS, Environm Syst Biol Grp, Lab Mol Toxicol, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 878 EP 879 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800034 ER PT J AU Crawley, JN AF Crawley, Jacqueline N. TI Defining mouse behaviors related autism. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res C1 NIMH, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 892 EP 892 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800070 ER PT J AU Kimmel, CA AF Kimmel, Carole A. TI Update on the national children's study. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res C1 NICHHD, NIH, DHHS, Natl Childrens Study Program Off, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 894 EP 895 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800077 ER PT J AU Gohlke, JM Parham, FM Portier, CJ AF Gohlke, Julia M. Parham, Fredrick M. Portier, Christopher J. TI A direct comparison of algorithm-based and literature-based systems biology approaches: Applications in neurodevelopment. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE computational; microarray and forebrain C1 NIEHS, Mol Toxicol Lab, Syst Biol Grp, Res Triangle Pk, NC 27709 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 908 EP 908 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800102 ER PT J AU Johnson, K Ryan, L Davis, J Elmore, A Guenther, B Marcus, J Maronpot, R AF Johnson, K. Ryan, L. Davis, J. Elmore, A. Guenther, B. Marcus, J. Maronpot, R. TI Application of magnetic resonance imaging in developmental neurotoxicity testing: A pilot study. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE MR imaging; stereology; methylazoxymethanol acetate C1 NIEHS, Lab Expt Pathol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. MRPath Inc, Durham, NC USA. Integrated Lab Syst Inc, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 909 EP 909 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800105 ER PT J AU McPherson, CA Wine, RN d'Hellencourt, CL Harry, GJ AF McPherson, C. A. Wine, R. N. d'Hellencourt, C. L. Harry, G. J. TI Micgroglia activation and fate following TMT-induced neurodegeration in the mouse hippocampus. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE neurodegeneration; microglia; mouse C1 NIEHS, NIH, DHHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 919 EP 919 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800131 ER PT J AU Brunssen, SH Moy, SS Harry, GJ AF Brunssen, S. H. Moy, S. S. Harry, G. J. TI Behavioral effects of direct exposure of CNS to hyper-IL-6 in the perinatal CD-1 mouse. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE neuroinflammation; development; behavior C1 NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 926 EP 926 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800149 ER PT J AU Wine, RN d'Hellencourt, CL McPherson, CA Harry, GJ AF Wine, Robert N. d'Hellencourt, Christian Lefebvre McPherson, Christopher A. Harry, G. Jean TI Cytokine receptor expression and glial contact following acute hippocampal injury. SO NEUROTOXICOLOGY LA English DT Meeting Abstract CT 22nd International Neurotoxicology Conference CY SEP 11-14, 2005 CL Res Triangle Park, NC SP Natl Inst Environm Hlth Sci, USA Med Res & Mat Command, USA Res Inst Environm Med, Ctr Hlth Res, Res Fdn Hlth & Environm Effect, Aurism Soc Amer, CDC/Natl Ctr Environm Hlth & ATSDR, BUG/NIEHS Superfund Basic Res Program, NIH/Natl Inst Neurol Disorder & Stroke, March Dimes Birth Defects Fdn, Manganese Hlth Res Program, Elsevier Sci, Elect Power Res Inst, US Tuna Fdn, Amer Chem Council, Polychlorinated Biphenyls Panel, Ctr Toxicol & Environm Hlth, Charles River DDS, Argus Div, NIH/Natl Inst Child Hlth & Human Dev, Soc Toxicol, Arkansas Childrens Hosp, FDA/Natl Ctr Toxicol Res DE glial contact; cytokines; neurodegeneration C1 NIEHS, Neurobiol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2006 VL 27 IS 5 SI SI BP 927 EP 928 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 082SZ UT WOS:000240408800153 ER PT J AU Bradfield, JY West, JR Maier, SE AF Bradfield, James Y. West, James R. Maier, Susan E. TI Uptake and elimination of ethanol by young zebrafish embryos SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE embryonic development; fetal alcohol syndrome; alcohol; teratogenesis; metabolism ID ALCOHOL; RATS; PERMEABILITY; EXPOSURE; MICE AB Among animal models being explored to understand ethanol-induced teratogenesis, the zebrafish (Danio rerio) is attracting attention because its embryonic development is well characterized and readily visualized. Despite the potential of the zebrafish embryo in research on developmental anomalies produced by ethanol exposure, little is known about the relationship between embryonic ethanol content and the nature/severity of ethanol-mediated deficits. Here, using gas chromatography and radiometry of labeled ethanol carbon, we examine accumulation and clearance of ethanol by dechorionated zebrafish embryos during blastulation/gastrulation. Our data indicate that: (a) rates of uptake and loss of ethanol are directly proportional to the extra-/intra-embryonic ethanol concentration gradient and (b) ethanol in the water fraction of embryos reaches near equimolarity with ethanol in the exposure medium. It appears that, within a wide range of exposure concentrations, embryonic ethanol content can be predicted accurately according to exposure time. Furthermore, it appears that embryonic ethanol can be adjusted rapidly to and maintained at a targeted concentration. circle dot 2006 Elsevier Inc. All rights reserved. C1 Texas A&M Univ, Coll Med, Syst Hlth Sci Sci, Dept Human Anat & Med Neurobiol, College Stn, TX 77843 USA. RP Maier, SE (reprint author), NIAAA, Off Director, NIH, 5635 Fishers Lane,Suite 2017, Bethesda, MD 20892 USA. EM maiers@mail.nih.gov FU PHS HHS [10090] NR 19 TC 17 Z9 17 U1 0 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 2006 VL 28 IS 5 BP 629 EP 633 DI 10.1016/j.ntt.2006.06.004 PG 5 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 115OG UT WOS:000242743000013 PM 16916596 ER PT J AU Jeang, KT Yedavalli, V AF Jeang, Kuan-Teh Yedavalli, Venkat TI Role of RNA helicases in HIV-1 replication SO NUCLEIC ACIDS RESEARCH LA English DT Article; Proceedings Paper CT Meeting on Helicases and NTP-Driven Nucleic Acid Machines CY JUL, 2005 CL Arolla, SWITZERLAND ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEAD-BOX PROTEIN; HEPATITIS-C VIRUS; EXPANDED FAT NUCLEOSIDE; NUCLEAR-PORE COMPLEX; VIRAL MESSENGER-RNA; WEST-NILE VIRUS; REV PROTEIN; TARGET SEQUENCE; TRANSCRIPTIONAL REGULATION AB Viruses are replication competent genomes which are relatively gene-poor. Even the largest viruses (i.e. Herpesviruses) encode only slightly > 200 open reading frames (ORFs). However, because viruses replicate obligatorily inside cells, and considering that evolution may be driven by a principle of economy of scale, it is reasonable to surmise that many viruses have evolved the ability to co-opt cell-encoded proteins to provide needed surrogate functions. An in silico survey of viral sequence databases reveals that most positive-strand and double-stranded RNA viruses have ORFs for RNA helicases. On the other hand, the genomes of retroviruses are devoid of virally-encoded helicase. Here, we review in brief the notion that the human immunodeficiency virus (HIV-1) has adopted the ability to use one or more cellular RNA helicases for its replicative life cycle. C1 NIAID, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 95 TC 36 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2006 VL 34 IS 15 BP 4198 EP 4205 DI 10.1093/nar/gkl398 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 090DB UT WOS:000240929700019 PM 16935887 ER PT J AU Fortune, JM Stith, CM Kissling, GE Burgers, PMJ Kunkel, TA AF Fortune, John M. Stith, Carrie M. Kissling, Grace E. Burgers, Peter M. J. Kunkel, Thomas A. TI RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase delta SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CELL NUCLEAR ANTIGEN; REPLICATION FACTOR-C; SACCHAROMYCES-CEREVISIAE; ACCESSORY PROTEINS; BASE SUBSTITUTION; III HOLOENZYME; CALF THYMUS; FIDELITY; PROCESSIVITY; MUTATIONS AB In fulfilling its biosynthetic roles in nuclear replication and in several types of repair, DNA polymerase delta (pol delta) is assisted by replication protein A (RPA), the single-stranded DNA-binding protein complex, and by the processivity clamp proliferating cell nuclear antigen (PCNA). Here we report the effects of these accessory proteins on the fidelity of DNA synthesis in vitro by yeast pol delta. We show that when RPA and PCNA are included in reactions containing pol delta, rates for single base errors are similar to those generated by pol delta alone, indicating that pol delta itself is by far the prime determinant of fidelity for single base errors. However, the rate of deleting multiple nucleotides between directly repeated sequences is reduced by similar to 10-fold in the presence of either RPA or PCNA, and by >= 90-fold when both proteins are present. We suggest that PCNA and RPA suppress large deletion errors by preventing the primer terminus at a repeat from fraying and/or from relocating and annealing to a downstream repeat. Strong suppression of deletions by PCNA and RPA suggests that they may contribute to the high replication fidelity needed to stably maintain eukaryotic genomes that contain abundant repetitive sequences. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Struct Biol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Washington Univ, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Kunkel, TA (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM32431, R01 GM032431] NR 40 TC 42 Z9 42 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2006 VL 34 IS 16 BP 4335 EP 4341 DI 10.1093/nar/gkl403 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094ZE UT WOS:000241277200008 PM 16936322 ER PT J AU Koska, J de Courten, B Wake, DJ Nair, S Walker, BR Bunt, JC Permana, PA Lindsay, RS Tataranni, PA AF Koska, Juraj de Courten, Barbora Wake, Deborah J. Nair, Saraswathy Walker, Brian R. Bunt, Joy C. Permana, Paska A. Lindsay, Robert S. Tataranni, P. Antonio TI 11 beta-hydroxysteroid dehydrogenase type 1 in adipose tissue and prospective changes in body weight and insulin resistance SO OBESITY LA English DT Article DE adipocytes; glucocorticoids; homeostasis; model assessment of insulin resistance; Pima Indians; adipose tissue ID OBESE ZUCKER RATS; CORTISOL METABOLISM; VISCERAL OBESITY; FAT DISTRIBUTION; ADIPOCYTE SIZE; PIMA-INDIANS; EXPRESSION; MICE; GLUCOCORTICOIDS; DIFFERENTIATION AB Objective: Increased mRNA and activity levels of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11 beta HSD1 expression or activity in abdominal subcutaneous AT of non-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]. Research Methods and Procedures: Prospective analyses were performed in 20 subjects (two whites and 18 Pima Indians) who had baseline measurements of 11 beta HSD1 mRNA and activity in whole AT (follow-up, 0.3 to 4.9 years) and in 47 Pima Indians who had baseline assessments of 11 beta HSD1 mRNA in isolated adipocytes (follow-up, 0.8 to 5.3 years). Results: In whole AT, although 11 beta HSD1 mRNA levels showed positive associations with changes in weight and HOMA-IR, 11 beta HSD1 activity was associated with changes in HOMA-IR but not in body weight. 11 beta HSD1 mRNA levels in isolated adipocytes were not associated with follow-up changes in any of the anthropometric or metabolic variables. Discussion: Our results indicate that increased expression of 11 beta HSD1 in subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin resistance. This prospective relationship does not seem to be mediated by increased 11 beta HSD1 expression in adipocytes. C1 NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA. Univ Edinburgh, Western Gen Hosp, Endocrinol Unit, Div Med Sci, Edinburgh, Midlothian, Scotland. RP Koska, J (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, NIH, 4212 N 16th St,Room 5-41, Phoenix, AZ 85016 USA. EM jkoska@mail.nih.gov FU Intramural NIH HHS NR 36 TC 14 Z9 14 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD SEP PY 2006 VL 14 IS 9 BP 1515 EP 1522 DI 10.1038/oby.2006.175 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 097QG UT WOS:000241462500008 PM 17030962 ER PT J AU Guo, Y Ma, LJ Enriori, PJ Koska, J Franks, PW Brookshire, T Cowley, MA Salbe, AD DelParigi, A Tataranni, PA AF Guo, Yan Ma, Lijun Enriori, Pablo J. Koska, Juraj Franks, Paul W. Brookshire, Thomas Cowley, Michael A. Salbe, Arline D. DelParigi, Angelo Tataranni, P. Antonio TI Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans SO OBESITY LA English DT Article DE peptide YY; body weight; energy homeostasis ID INHIBITS FOOD-INTAKE; RESPIRATORY CHAMBER; PLASMA GHRELIN; NEUROPEPTIDE-Y; GUT HORMONE; RECEPTOR; PYY3-36; OBESITY; WEIGHT; EXPENDITURE AB Objective: To explore the potential role of the endogenous peptide YY (PYY) in the long-term regulation of body weight and energy homeostasis. Research Methods and Procedures: Fasting and postprandial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21 men/8 women) non-diabetic subjects, 16 of whom had a follow-up visit 10.8 +/- 1.4 months later. Ratings of hunger and satiety were collected using visual analog scales. Resting metabolic rate (RMR) (15-hour RMR) and respiratory quotient (RQ) were assessed using a respiratory chamber. Results: Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15-hour RMR (r = -0.46, p = 0.01). Postprandial changes in PYY (area under the curve) were positively associated with postprandial changes in ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved after the meal (peak PYY) were negatively associated with 24-hour RQ (r = -0.41, p = 0.03). Prospectively, the peak PYY concentrations were negatively associated with changes in body weight (r = -0.58, p = 0.01). Discussion: Our data indicate that the endogenous PYY may be involved in the long-term regulation of body weight. It seems that this long-term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism. C1 NIDDKD, Obes & Diabet Clin Res Sect, NIH, US Dept HHS, Phoenix, AZ 85016 USA. Oregon Hlth Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR USA. Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Med, Inst Publ Hlth & Clin Med, S-90185 Umea, Sweden. RP Guo, Y (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, NIH, US Dept HHS, 4212 N 16th St, Phoenix, AZ 85016 USA. EM yanguo@phx.niddk.nih.gov RI Cowley, Michael/B-9428-2008 OI Cowley, Michael/0000-0001-7811-134X FU Intramural NIH HHS NR 35 TC 55 Z9 55 U1 1 U2 3 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD SEP PY 2006 VL 14 IS 9 BP 1562 EP 1570 DI 10.1038/oby.2006.180 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 097QG UT WOS:000241462500013 PM 17030967 ER PT J AU Tsutsui, TW Inaba, T Fisher, LW Robey, PG Tsutsui, T AF Tsutsui, Takeo W. Inaba, Tomohiro Fisher, Larry W. Robey, Pamela Gehron Tsutsui, Takeki TI In vitro chromosome aberration tests using human dental pulp cells to detect the carcinogenic potential of chemical agents SO ODONTOLOGY LA English DT Article DE human dental pulp cells; chromosome aberrations; genetic toxicity; mitomycin C; cyclophosphamide ID HAMSTER EMBRYO CELLS; SISTER-CHROMATID EXCHANGES; UNSCHEDULED DNA-SYNTHESIS; MITOMYCIN-C; TRANSFORMATION; ACTIVATION; CYCLOPHOSPHAMIDE; GENOTOXICITY; INDUCTION; CULTURES AB To examine if human dental pulp cells are useful for assessing the carcinogenic potential of chemical agents, we cultured human dental pulp cells from adults and studied the ability of chemical agents known to be carcinogenic to induce chromosome aberrations in these cells. We confirmed that human dental pulp cells in primary or secondary cultures had the capability of accumulating calcium in vitro as detected by Alizarin red staining and generating dentin-like tissue in immunocompromised mice. These phenotypes were maintained even in cells at seven passages. Next, we examined if chromosome aberrations were induced by exposure of human dental pulp cells (designated here as D824 cells) at seven to nine passages to chemical agents with carcinogenic activity. Statistically significant increases in the frequencies of chromosome aberrations were induced in D824 cells treated with a direct-acting carcinogen, mitomycin C, for 3 h. Chromosome aberrations were also induced at statistically significant levels in D824 cells treated with an indirect-acting carcinogen, cyclophosphamide, for 2 h in the presence of exogenous metabolic activation with rat liver postmitochondrial supernatant. Cyclophosphamide failed to induce chromosome aberrations in the absence of exogenous metabolic activation. Although the reliability of chromosome aberration tests using human dental pulp cells remains to be validated by studying the ability of various other chemical agents with or without carcinogenic activity to induce chromosome aberrations, this chromosome aberration test system may be useful for carcinogenic risk assessment in the target cells. C1 Nippon Dent Univ Tokyo, Dept Pharmacol, Sch Life Dent Tokyo, Chiyoda Ku, Tokyo 1028159, Japan. Nippon Dent Univ Hosp Tokyo, Tokyo, Japan. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, US Dept HHS, Bethesda, MD USA. RP Tsutsui, T (reprint author), Nippon Dent Univ Tokyo, Dept Pharmacol, Sch Life Dent Tokyo, Chiyoda Ku, 1-9-20 Fujimi, Tokyo 1028159, Japan. EM takeki@tokyo.ndu.ac.jp RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 29 TC 13 Z9 16 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1618-1247 J9 ODONTOLOGY JI Odontology PD SEP PY 2006 VL 94 IS 1 BP 44 EP 50 DI 10.1007/s10266-006-0065-1 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 112OT UT WOS:000242536500006 PM 16998617 ER PT J AU Karakas, B Weeraratna, A Abukhdeir, A Blair, BG Konishi, H Arena, S Becker, K Wood, W Argani, P De Marzo, AM Bachman, KE Park, BH AF Karakas, B. Weeraratna, A. Abukhdeir, A. Blair, B. G. Konishi, H. Arena, S. Becker, K. Wood, W., III Argani, P. De Marzo, A. M. Bachman, K. E. Park, B. H. TI Interleukin-1 alpha mediates the growth proliferative effects of transforming growth factor-beta in p21 null MCF-10A human mammary epithelial cells SO ONCOGENE LA English DT Article DE p21; TGF-beta; IL-1alpha; breast cancer ID BREAST-CANCER CELLS; TGF-BETA; CYCLE ARREST; EXPRESSION; BINDING; GENE; REPRESSION; TGF-BETA-1; LINES; CDK AB Transforming growth factor-beta type 1 (TGF-beta) has been implicated as both a tumor suppressor and a tumor promoter in many solid epithelial cancers. We have previously demonstrated that the cyclin dependent kinase (CDK) inhibitor p21 acts as a molecular switch in determining a growth inhibitory versus growth proliferative response to TGF-beta in the spontaneously immortalized human mammary epithelial cell line MCF-10A. We now demonstrate that this proliferative effect of TGF-beta is mediated through the proinflammatory cytokine, interleukin-1 alpha (IL-1 alpha). Using gene expression array analysis, we identified IL-1 alpha as a cytokine specifically upregulated only in cells lacking p21 and only upon TGF-beta stimulation. Cell proliferation assays verified that recombinant IL-1 alpha was capable of inducing a growth proliferative response in p21 null MCF-10A cells, while neutralizing antibodies against IL-1 alpha prevented the growth proliferative effects of TGF-beta. Mechanistically, both the CDK and proliferating cell nuclear antigen (PCNA) inhibitory functions of p21 were responsible for preventing TGF-beta induced cell proliferation, but only PCNA inhibition by p21 regulated IL-1 alpha gene expression. These studies demonstrate a novel role for IL-1 alpha in mediating a proliferative response to TGF-beta signaling, and suggest that therapies directed against IL-1 alpha could abate the growth proliferative effects of TGF-beta without compromising its tumor suppressive function. C1 Johns Hopkins Univ, Dept Oncol, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. NIA, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Pathol, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21231 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Park, BH (reprint author), Johns Hopkins Univ, Dept Oncol, Sch Med, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, 1650 Orleans St,Room 1M42, Baltimore, MD 21231 USA. EM bpark2@jhmi.edu RI arena, sabrina/H-4985-2012; OI Konishi, Hiroyuki/0000-0003-1131-4905; Becker, Kevin/0000-0002-6794-6656; ARENA, Sabrina/0000-0002-1318-2494 FU Intramural NIH HHS; NCI NIH HHS [P50 CA88843, R01CA109274-01A2] NR 23 TC 13 Z9 13 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 2006 VL 25 IS 40 BP 5561 EP 5569 DI 10.1038/sj.onc.1209540 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 082EV UT WOS:000240370400009 PM 16619041 ER PT J AU Baid, SK Nieman, LK AF Baid, S. K. Nieman, L. K. TI Therapeutic doses of glucocorticoids: implications for oral medicine SO ORAL DISEASES LA English DT Review DE glucocorticoids; adrenal insufficiency; inhaled corticosteroids; steroid supplementation; hypothalamic-pituitary-adrenal axis ID CORTISOL PRODUCTION-RATE; ADRENAL INSUFFICIENCY; MASS-SPECTROMETRY; CORTICOSTEROIDS; DISEASE; ACTH AB Glucocorticoids can cause adverse systemic side-effects ranging from iatrogenic Cushing's syndrome during treatment, to hypothalamic-pituitary-adrenal axis suppression and clinically significant adrenal insufficiency when the agents are discontinued. While the oral route of administration is most often implicated, it is now becoming more apparent that inhaled and topical administration also can cause these effects. Given the high therapeutic value of glucocorticoids, the ability to prescribe these agents while maintaining a low risk-to-benefit ratio for patients is critical. The aim of this review is to provide oral healthcare practitioners with a practical guide to commonly used glucocorticoids, their adverse effects, and perioperative use. C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. RP Nieman, LK (reprint author), Bldg 10,CRC 1E-3140 MSC 1109,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@nih.gov FU Intramural NIH HHS NR 32 TC 17 Z9 17 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD SEP PY 2006 VL 12 IS 5 BP 436 EP 442 DI 10.1111/j.1601-0825.2006.01290.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 073YJ UT WOS:000239778400002 PM 16910913 ER PT J AU Grandis, JR Battey, JF Califf, RM Chole, RA Gantz, BJ Gates, GA Gorelic, L Hannley, MT Hardwick, KS Harris, JP Kapoor, WN Lai, SY Lalwani, AK Minor, LB Nadol, JP Post, JC Roland, PS Schechter, AM Schuller, DE Sklare, DA Wackym, PA Weber, RS Weymuller, EA Wolf, GT Woodson, GE AF Grandis, Jennifer R. Battey, James F. Califf, Robert M. Chole, Richard A. Gantz, Bruce J. Gates, George A. Gorelic, Lester Hannley, Maureen T. Hardwick, Kevin S. Harris, Jeffrey P. Kapoor, Wishwa N. Lai, Stephen Y. Lalwani, Anil K. Minor, Lloyd B. Nadol, Joseph P. Post, J. Christopher Roland, Peter S. Schechter, Alan M. Schuller, David E. Sklare, Daniel A. Wackym, P. Ashley Weber, Randal S. Weymuller, Ernest A., Jr. Wolf, Gregory T. Woodson, Gayle E. TI Research education and training in otolaryngology: Meeting summary and research opportunities SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID RESIDENCY C1 Univ Pittsburgh, Inst Canc, Dept Otolaryngol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Inst Canc, Dept Pharmacol, Pittsburgh, PA 15260 USA. NIDCD, Bethesda, MD USA. Duke Univ, Duke Clin Res Inst, Dept Otolaryngol, Durham, NC USA. Washington Univ, St Louis, MO USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. Univ Washington, Dept Otolaryngol, Seattle, WA 98195 USA. NCI, Canc Training Branch, Bethesda, MD 20892 USA. Amer Acad Otolaryngol Head & Neck Surg Fdn, Alexandria, VA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Calif San Diego, Dept Otolaryngol, San Diego, CA 92103 USA. Univ Pittsburgh, Dept Internal Med, Pittsburgh, PA 15260 USA. NYU, Dept Otolaryngol, New York, NY 10016 USA. NYU, Dept Physiol, New York, NY USA. NYU, Dept Neurosci, New York, NY USA. Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21218 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Drexel Univ, Coll Med, Dept Otolaryngol, Philadelphia, PA 19104 USA. Drexel Univ, Coll Med, Ctr Genom Sci, Philadelphia, PA 19104 USA. Univ Texas SW, Dept Otolaryngol, Dallas, TX USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Otolaryngol, Columbus, OH 43210 USA. Med Coll Wisconsin, Dept Otolaryngol, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Commun Sci & Physiol, Milwaukee, WI 53226 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Univ Michigan, Dept Otorhinolaryngol, Ann Arbor, MI 48109 USA. So Illinois Univ, Div Otolaryngol, Dept Surg, Springfield, IL 62794 USA. Univ Pittsburgh, Ctr Canc, Dept Otolaryngol, Pittsburgh, PA 15213 USA. RP Grandis, JR (reprint author), Univ Pittsburgh, Ctr Canc, Dept Otolaryngol, Suite 500,Eye & Ear Inst Bldg,200 Lothrop St, Pittsburgh, PA 15213 USA. EM jgrandis@pitt.edu OI Woodson, Gayle/0000-0002-0315-5329; Roland, Peter/0000-0003-4152-7346 NR 5 TC 9 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2006 VL 135 IS 3 BP 361 EP 367 DI 10.1016/j.otohns.2006.05.014 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 082FF UT WOS:000240371400004 PM 16949965 ER PT J AU O'Meara, WP Remich, S Ogutu, B Lucas, M Mtalib, R Obare, P Oloo, F Onoka, C Osoga, J Ohrt, C McKenzie, FE AF O'Meara, Wendy Prudhomme Remich, Shon Ogutu, Bernhards Lucas, Martin Mtalib, Ramadan Obare, Peter Oloo, Frederick Onoka, Caroline Osoga, Joseph Ohrt, Colin McKenzie, F. Ellis TI Systematic comparison of two methods to measure parasite density from malaria blood smears SO PARASITOLOGY RESEARCH LA English DT Article ID MICROSCOPY AB This study was designed to directly compare the accuracy, reproducibility, and efficiency of three methods commonly used to measure blood-stage malaria parasite density from Giemsa-stained blood films. Parasites and white blood cells (WBCs) were counted in 154 thick films by two independent microscopists. Forty-six slides were read by counting parasitized red blood cells (RBCs) in the thin film. Using these same slides, parasites were again counted by two independent microscopists using an ocular grid. Overall, parasite densities were significantly lower and discrepancy between readers was higher when using the grid method compared to the WBC method, but there was no difference when compared to the RBC method. When one reader who had difficulty with the grid method was excluded, the discrepancy between readers was equivalent for the three methods. Densities and discrepancy between readers were indistinguishable when parasites were counted until 200 or 500 WBCs. Counting beyond 200 WBCs may not significantly improve parasite density measurements. Using an ocular grid directly measures parasites per volume rather than using a WBC per microliter conversion factor and eliminates the need to switch from the thick film to the thin film for high parasitemias. However, significant differences in densities measured by the grid method and the WBC method need to be evaluated. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Kenya Govt Med Res Ctr, Med Res Unti Kenya, Clin Res Ctr, USA,Walter Reed Project,Malaria Micrsocopy Ctr Ex, Kisumu, Kenya. Kenya Govt Med Res Ctr, Ctr Dis Control, Kisumu, Kenya. Walter Reed Army Inst Res, Silver Spring, MD USA. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM prudhomw@mail.nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 9 TC 17 Z9 17 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0932-0113 J9 PARASITOL RES JI Parasitol. Res. PD SEP PY 2006 VL 99 IS 4 BP 500 EP 504 DI 10.1007/s00436-006-0135-x PG 5 WC Parasitology SC Parasitology GA 084SQ UT WOS:000240555100032 PM 16572338 ER PT J AU Linet, MS Hauptmann, M Freedman, DM Alexander, BH Miller, J Sigurdson, AJ Doody, MM AF Linet, Martha S. Hauptmann, Michael Freedman, D. Michal Alexander, Bruce H. Miller, Jeremy Sigurdson, Alice J. Doody, Michele Morin TI Interventional radiography and mortality risks in US radiologic technologists SO PEDIATRIC RADIOLOGY LA English DT Article; Proceedings Paper CT 3rd ALARA Conference CY FEB 11-12, 2006 CL Orlando, FL SP Soc Pediat Radiol, NCI DE radiologic technologists; interventional radiography; occupational radiation exposure; mortality ID X-RAY WORKERS; CANCER INCIDENCE; UNITED-STATES; BRITISH RADIOLOGISTS; RADIATION EXPOSURE; DISEASE; FOLLOW; HEALTH; DEATH; CHINA AB With the exponential increase in minimally invasive fluoroscopically guided interventional radiologic procedures, concern has increased about the health effects on staff and patients of radiation exposure from these procedures. There has been no systematic epidemiologic investigation to quantify serious disease risks or mortality. To quantify all-cause, circulatory system disease and cancer mortality risks in U.S. radiologic technologists who work with interventional radiographic procedures, we evaluated mortality risks in a nationwide cohort of 88,766 U.S. radiologic technologists (77% female) who completed a self-administered questionnaire during 1994-1998 and were followed through 31 December 2003. We obtained information on work experience, types of procedures (including fluoroscopically guided interventional procedures), and protective measures plus medical, family cancer history, lifestyle, and reproductive information. Cox proportional hazards regression models were used to compute relative risks (RRs) with 95% confidence intervals (CIs). Between completion of the questionnaire and the end of follow-up, there were 3,581 deaths, including 1,209 from malignancies and 979 from circulatory system diseases. Compared to radiologic technologists who never or rarely performed or assisted. with fluoroscopically guided interventional procedures, all-cause mortality risks were not increased among those working on such procedures daily. Similarly, there was no increased risk of mortality resulting from all circulatory system diseases combined, all cancers combined, or female breast cancer among technologists who daily performed or assisted with fluoroscopically guided interventional procedures. Based on small numbers of deaths (n=151), there were non-significant excesses (40%-70%) in mortality from cerebrovascular disease among technologists ever working with these procedures. The absence of significantly elevated mortality risks in radiologic technologists reporting the highest frequency of interventional radiography procedures must be interpreted cautiously in light of the small number of deaths during the relatively short follow-up. The present study cannot rule out increased risks of cerebrovascular disease, specific cancers, and diseases with low case-fatality rates or a long latency period preceding death. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. Informat Management Serv Inc, Rockville, MD USA. RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7048, Bethesda, MD 20892 USA. EM linetm@mail.nih.gov FU NCI NIH HHS [N01-CP-51016, N01-CP-15673, N02-CP-81121] NR 40 TC 7 Z9 7 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2006 VL 36 SU 2 BP 113 EP 120 DI 10.1007/s00247-006-0224-0 PG 8 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 088IJ UT WOS:000240805100003 PM 16862404 ER PT J AU Kleinerman, RA AF Kleinerman, Ruth A. TI Cancer risks following diagnostic and therapeutic radiation exposure in children SO PEDIATRIC RADIOLOGY LA English DT Article; Proceedings Paper CT 3rd ALARA Conference CY FEB 11-12, 2006 CL Orlando, FL SP Soc Pediat Radiol, NCI DE radiation risks; carcinogenesis; diagnostic radiation; therapeutic radiation ID INDUCED THYROID-CANCER; 2 SWEDISH COHORTS; X-RAY TREATMENT; BREAST-CANCER; IONIZING-RADIATION; SKIN HEMANGIOMA; POOLED ANALYSIS; CARDIAC-CATHETERIZATION; FLUOROSCOPIC EXAMINATIONS; CHILDHOOD LEUKEMIA AB The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, EPS 7044,6120 Execut Blvd, Rockville, MD 20852 USA. EM kleinerr@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 FU Intramural NIH HHS NR 32 TC 214 Z9 222 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2006 VL 36 SU 2 BP 121 EP 125 DI 10.1007/s00247-006-0191-5 PG 5 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 088IJ UT WOS:000240805100004 PM 16862418 ER PT J AU Thierry-Chef, I Simon, SL Miller, DL AF Thierry-Chef, Isabelle Simon, Steven L. Miller, Donald L. TI Radiation dose and cancer risk among pediatric patients undergoing interventional neuroradiology procedures SO PEDIATRIC RADIOLOGY LA English DT Article; Proceedings Paper CT 3rd ALARA Conference CY FEB 11-12, 2006 CL Orlando, FL SP Soc Pediat Radiol, NCI DE brain radiation exposure; neurointerventional procedures; lifetime risk radiation-induced carcinogenesis ID RADIOLOGY PROCEDURES; RAD-IR; DIAGNOSTIC-RADIOLOGY; BRAIN; HEAD AB Background: During interventional neuroradiology procedures, patients can be exposed to moderate to high levels of radiation. Special considerations are required to protect children, who are generally more sensitive to the short- and long-term detrimental effects of radiation exposure. Estimates of dose to the skin of children from certain interventional procedures have been published elsewhere, but we are not aware of data on dose to the brain or on the long-term risk of cancer from brain radiation. Objectives: Our goals were to estimate radiation doses to the brain in 50 pediatric patients who had undergone cerebral embolization and to assess their lifetime risks of developing radiation-related brain cancer. Materials and methods: Entrance-peak skin dose and various assumptions on conditions of exposure were used as input for dosimetric calculations to estimate the spatial pattern of dose within the brain and the average dose to the whole brain for each child. The average dose and the age of the child at time of exposure were used to estimate the lifetime risk of developing radiation-related brain cancer. Results: Among the 50 patients, average radiation doses to the brain were estimated to vary from 100 mGy to 1,300 mGy if exposed to non-collimated fields and from 20 mGy to 160 mGy for collimated, moving fields. The lifetime risk of developing brain cancer was estimated to be increased by 2% to 80% as a result of the exposure. Given the very small lifetime background risk of brain tumor, the excess number of cases will be small even though the relative increase might be as high as 80%. Conclusion: ALARA principles of collimation and dose optimization are the most effective means to minimize the risk of future radiation-related cancer. C1 NCI, Radiat Epidemiol Branch, Div Epidemiol & Genet, Rockville, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20814 USA. RP Thierry-Chef, I (reprint author), 18 Domaine Cote, F-69530 Brignais, France. EM thierrychef@hotmail.com NR 9 TC 28 Z9 30 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD SEP PY 2006 VL 36 SU 2 BP 159 EP 162 DI 10.1007/s00247-006-0206-2 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 088IJ UT WOS:000240805100010 PM 16862414 ER PT J AU Emons, JAM Marino, R Nilsson, O Barnes, KM Even-Zohar, N Andrade, AC Chatterjee, NA Wit, JM Karperien, M Baron, J AF Emons, Joyce A. M. Marino, Rose Nilsson, Ola Barnes, Kevin M. Even-Zohar, Naomi Andrade, Anenisia C. Chatterjee, Neal A. Wit, Jan M. Karperien, Marcel Baron, Jeffrey TI The role of p27Kip1 in the regulation of growth plate chondrocyte proliferation in mice SO PEDIATRIC RESEARCH LA English DT Article ID CELL-CYCLE; P27(KIP1)-DEFICIENT MICE; BONE-GROWTH; EXPRESSION; P27(KIP1); HORMONE; DIFFERENTIATION; P21(CIP1/WAF1); ACTIVATION; INHIBITORS AB p27/Kip1, a cyclin-dependent kinase inhibitor, negatively regulates proliferation of multiple cell types. The goal of this study was to assess the role of p27 in the spatial, temporal, and conditional regulation of growth plate chondrocyte proliferation. p27 mRNA expression was detected by real-time RT-PCR in all zones of the mouse growth plate at levels approximately 2-fold lower than in the surrounding bone. To determine whether this expression is physiologically important, we studied skeletal growth in 7-wk-old mice lacking a functional p27 gene. In these mice, body length was modestly increased and proliferation of proximal tibial growth plate chondrocytes was increased, but tibia length was not significantly greater than in controls. p27 ablation had no measurable effect on growth plate morphology. Treatment with dexamethasone inhibited longitudinal bone growth similarly in p27-deficient mice and controls, indicating that p27 is not required for the inhibitory effects of glucocorticoids on longitudinal growth. p27-deficient mice had increased width of the femoral diaphysis, suggesting that p27 acts normally to inhibit periosteal bone growth. In conclusion, our findings suggest that p27 has modest inhibitory effects on growth plate chondrocyte proliferation but is not required for the spatial or temporal regulation of proliferation or the conditional regulation by glucocorticoid. C1 NICHHD, Dev Endocrinol Branch, NIH, Gaithersburg, MD 20899 USA. Leiden Univ, Med Ctr, Dept Pediat, NL-2300 WB Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Endocrinol & Metab Dis, NL-2300 WB Leiden, Netherlands. RP Emons, JAM (reprint author), Willem Alexander Kinder Jeugdcent, Postzone 16-S,POB 9600, NL-2300 RG Leiden, Netherlands. EM j.emons@lumc.nl OI Nilsson, Ola/0000-0002-9986-8138 FU Intramural NIH HHS NR 30 TC 9 Z9 9 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2006 VL 60 IS 3 BP 288 EP 293 DI 10.1203/01.pdr.0000232790.53527.c6 PG 6 WC Pediatrics SC Pediatrics GA 075CW UT WOS:000239861300009 PM 16857774 ER PT J AU Pawlosky, RJ Lin, YH Llanos, A Mena, P Uauy, R Salem, N AF Pawlosky, Robert J. Lin, Yu Hong Llanos, Adolfo Mena, Patricia Uauy, Ricardo Salem, Norman, Jr. TI Compartmental analyses of plasma C-13- and H-2-labeled n-6 fatty acids arising from oral administrations of C-13-U-18 : 2n-6 and 2h5-20 : 3n-6 in newborn infants SO PEDIATRIC RESEARCH LA English DT Article ID TERM INFANTS; DOCOSAHEXAENOIC ACIDS; ARACHIDONIC-ACID; VISUAL-ACUITY; HUMAN-MILK; METABOLISM; CONVERSION; FORMULAS; HUMANS; GROWTH AB Efficacy of C-13-U-18:2n-6 and H-2(5)-20:3n-6 toward synthesis of labeled-20:4n-6 was studied in newborn infants utilizing compartmental models of plasma labeled n-6 fatty acids (FA). Ten infants received oral doses of C-13-U-18:2n-6 and H-2(5)-20:3n-6 ethyl esters (100 and 2 mg/kg, respectively). Rate constant coefficients and half-lives (t(2)/(1)) of n-6 FA were determined from the time-course concentrations of labeled-FA. Plasma n-6 FA values approximated steady state concentrations. Synthetic and utilization rates were calculated. Eight percent (range, 2-21%) of plasma (CU)-C-13-18:2n-6 was used for synthesis of C-13-18:3n-6, -20:2n-6, and -20:3n-6. Seventy percent of C-13-20:3n-6 (mean, CV: 0.26) was available for synthesis of C-13-20:4n-6. The percentage of (2)H(5)20:3n-6 converted to H-2(5)-20:4n-6 was lower (mean: 26%, p < 0.02) than the 13 C-labeled analogue. Turnover of 18:2n-6 in subjects and of 20:4n-6 in plasma was 4.2 g/kg/d (CV: 0.58) and 4.3 mg/kg/d (CV: 0.81), respectively. Intake of 18:2n-6 and 20:4n-6 were estimated to be 3.0 g/kg/d (+/- 1.7) and 2.8 mg/kg/d (+/- 2.2), respectively. Infants required additional 18:2n-6 and 20:4n-6 (mean: 1.2 g and 1.5 mg/kg/d) above predicted intake amounts to maintain plasma concentrations of 18:2n-6 and 20:4n-6, in order to spare FA from fat stores. C1 NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. INTA, Santiago 11, Chile. Hosp Dr Sotero del Rio, Neonatol Unit, Santiago 8207257, Chile. Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. RP Pawlosky, RJ (reprint author), Room 1S-22,5625 Fishers Lane, Bethesda, MD 20892 USA. EM bpawl@mail.nih.gov FU Intramural NIH HHS NR 24 TC 14 Z9 14 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2006 VL 60 IS 3 BP 327 EP 333 DI 10.1203/01.pdr.0000232782.09352.ef PG 7 WC Pediatrics SC Pediatrics GA 075CW UT WOS:000239861300016 PM 16857777 ER PT J AU Ries, M Clarke, JTR Whybra, C Timmons, M Robinson, C Schlaggar, BL Pastores, G Lien, YH Kampmann, C Brady, RO Beck, M Schiffmann, R AF Ries, Markus Clarke, Joe T. R. Whybra, Catharina Timmons, Margaret Robinson, Chevalia Schlaggar, Bradley L. Pastores, Gregory Lien, Y. Howard Kampmann, Christoph Brady, Roscoe O. Beck, Michael Schiffmann, Raphael TI Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease SO PEDIATRICS LA English DT Article DE lysosomal storage disease; therapy; stroke; pediatric; cardiac disease ID CLINICAL-MANIFESTATIONS; CARDIAC MANIFESTATIONS; OUTCOME SURVEY; RENAL-DISEASE; GALACTOSIDASE; SAFETY; VARIABILITY; DEFICIENCY; CHILDHOOD; INFUSION AB CONTEXT. Fabry disease is an X-linked multisystem disorder. Enzyme-replacement therapy in adults has limited efficacy in treating major sequelae of advanced Fabry disease, such as kidney failure or stroke. This prompted a study of the safety and efficacy of enzyme replacement at an earlier stage of Fabry disease. OBJECTIVES. Our purpose with this work was to evaluate safety and to explore efficacy of enzyme treatment with agalsidase alfa in pediatric patients with Fabry disease.METHODS. We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5 - 18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies. METHODS. We conducted a 6-month open-label study at 3 tertiary care centers with 24 children (19 boys and 5 girls) with a mean age of 11.8 (range: 6.5-18) years, to examine safety parameters, including infusion reactions and antiagalsidase alfa antibodies. RESULTS. Agalsidase alfa was well tolerated, and all of the patients completed the study. Six boys and 1 girl had mild-to-moderate infusion reactions. One boy developed transient immunoglobulin G antibodies against agalsidase alfa. The boys showed a significant reduction in plasma globotriaosylceramide on treatment. Mean estimated glomerular filtration rate, cardiac structure, and function were normal and did not change over 26 weeks. Heart rate variability, as determined by 2-hour ambulatory monitoring, was decreased in the boys compared with the girls at baseline. All indices of heart rate variability improved significantly in the boys. Three patients with anhidrosis, as determined by quantitative sudomotor axon reflex testing, developed sweating. Six of 11 patients could reduce or cease their use of antineuropathic analgesics. CONCLUSIONS. Enzyme replacement with agalsidase alfa was safe in this study. The exploratory efficacy analysis documented increased clearance of globotriaosylceramide and improvement of autonomic function. Prospective long-term studies are needed to assess whether enzyme replacement initiated early in patients with Fabry disease is able to prevent major organ failure in adulthood. C1 Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Mainz, Childrens Hosp, Ctr Lysomal Storage Dis, D-6500 Mainz, Germany. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. NYU, Dept Neurol, New York, NY 10016 USA. NYU, Dept Pediat, New York, NY 10016 USA. Univ Arizona, Dept Med, Tucson, AZ 85721 USA. RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM RS4e@nih.gov OI Ries, Markus/0000-0002-5054-5741 FU Intramural NIH HHS NR 53 TC 111 Z9 121 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 924 EP 932 DI 10.1542/peds.2005-2895 PG 9 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100009 PM 16950982 ER PT J AU Smith, LM LaGasse, LL Derauf, C Grant, P Shah, R Arria, A Huestis, M Haning, W Strauss, A Della Grotta, S Liu, J Lester, BM AF Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Grant, Penny Shah, Rizwan Arria, Amelia Huestis, Marilyn Haning, William Strauss, Arthur Della Grotta, Sheri Liu, Jing Lester, Barry M. TI The infant development, environment, and lifestyle study: Effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth SO PEDIATRICS LA English DT Article DE body weight; substance exposure; neonatal; prenatal; methamphetamine ID LOW-BIRTH-WEIGHT; FETAL-GROWTH; AMPHETAMINE ADDICTION; SOCIOECONOMIC-STATUS; GESTATIONAL-AGE; NEWBORN-INFANT; COCAINE USE; PREGNANCY; ALCOHOL; DETERMINANTS AB OBJECTIVE. Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development, Environment and Lifestyle study. DESIGN/ METHOD. The Infant Development, Environment and Lifestyle study screened 13 808 subjects at 4 clinical centers: 1618 were eligible and consented, among which 84 were methamphetamine exposed, and 1534 were unexposed. Those who were methamphetamine exposed were identified by self-report and/ or gas chromatography-mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Those who were unexposed denied amphetamine use and had a negative meconium screen. Both groups included prenatal alcohol, tobacco, or marijuana use, but excluded use of opiates, LSD, PCP or cocaine only. Neonatal parameters included birth weight and gestational age in weeks. One-way analysis of variance and linear-regression analyses were conducted on birth weight by exposure. The relationship of methamphetamine exposure and the incidence of small for gestational age was analyzed using multivariate logistic-regression analyses. RESULTS. The methamphetamine exposed group was 3.5 times more likely to be small for gestational age than the unexposed group. Mothers who used tobacco during pregnancy were nearly 2 times more likely to have small-for-gestational-age infants. In addition, less maternal weight gain during pregnancy was more likely to result in a small-for-gestational-age infant. Birthweight in the methamphetamine exposed group was lower than the unexposed group. CONCLUSIONS. These findings suggest that prenatal methamphetamine use is associated with fetal growth restriction after adjusting for covariates. Continued follow-up will determine if these infants are at increased risk for growth abnormalities in the future. C1 Harbor UCLA Med Ctr, Martin Res Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Torrance, CA USA. Women & Infants Hosp Rhode Isl, Brown Med Sch, Brown Ctr Study Children Risk, Providence, RI USA. Univ Hawaii, Dept Pediat, Honolulu, HI 96822 USA. Univ Hawaii, Dept Psychiat, John A Burns Sch Med, Honolulu, HI 96822 USA. Univ Oklahoma, Dept Pediat, Norman, OK 73019 USA. Blank Childrens Hosp Iowa Hlth, Dept Pediat, Des Moines, IA USA. Univ Maryland, Ctr Subst Abuse Res, College Pk, MD 20742 USA. Natl Inst Drug Abuse, Sect Chem & Drug Metab, Bethesda, MD USA. Long Beach Mem Med Ctr, Dept Pediat, Long Beach, CA USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Martin Res Ctr, Los Angeles Biomed Res Inst, 1124 W Carson St, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU NCRR NIH HHS [3 M01 RR00425, P20 RR11091]; NIDA NIH HHS [1R01DA014918, R01 DA014948] NR 45 TC 123 Z9 125 U1 1 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 1149 EP 1156 DI 10.1542/peds.2005-2564 PG 8 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100037 PM 16951010 ER PT J AU Raju, TNK Higgins, RD Stark, AR Leveno, KJ AF Raju, Tonse N. K. Higgins, Rosemary D. Stark, Ann R. Leveno, Kenneth J. TI Optimizing care and outcome for late-preterm (near-term) infants: A summary of the workshop sponsored by the National Institute of Child Health and Human Development SO PEDIATRICS LA English DT Article DE prematurity; low birth weight; preterm birth; near-term infant; late-preterm infant; seizures; kernicterus; respiratory distress syndrome; apnea; sudden infant death ID GESTATIONAL-AGE; BIRTH-WEIGHT; UNITED-STATES; RESPIRATORY-DISTRESS; NEONATAL MORBIDITY; RISK-FACTORS; MORTALITY; NEWBORNS; PREMATURE; BRAIN AB In 2003, 12.3% of births in the United States were preterm (< 37 completed weeks of gestation). This represents a 31% increase in the preterm birth rate since 1981. The largest contribution to this increase was from births between 34 and 36 completed weeks of gestation (often called the "near term" but referred to as "late preterm" in this article). Compared with term infants, late-preterm infants have higher frequencies of respiratory distress, temperature instability, hypoglycemia, kernicterus, apnea, seizures, and feeding problems, as well as higher rates of rehospitalization. However, the magnitude of these morbidities at the national level and their public health impact have not been well studied. To address these issues, the National Institute of Child Health and Human Development of the National Institutes of Health invited a multidisciplinary team of experts to a workshop in July 2005 entitled "Optimizing Care and Outcome of the Near-Term Pregnancy and the Near-Term Newborn Infant." The participants discussed the definition and terminology, epidemiology, etiology, biology of maturation, clinical care, surveillance, and public health aspects of late-preterm infants. Knowledge gaps were identified, and research priorities were listed. This article provides a summary of the meeting. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Pediat, Div Neonatol, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Obstet Gynecol, Dallas, TX 75235 USA. RP Raju, TNK (reprint author), 6100 Execut Blvd,4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 54 TC 313 Z9 341 U1 3 U2 17 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 1207 EP 1214 DI 10.1542/peds.2006-0018 PG 8 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100044 PM 16951017 ER PT J AU Twery, MJ AF Twery, Michael J. TI The cartoon character Garfield and the "sleep well. Do well. Star sleeper" campaign SO PEDIATRICS LA English DT Editorial Material C1 NHLBI, Natl Ctr Sleep Disorders Res, Two Rockledge Ctr, Bethesda, MD 20892 USA. NHLBI, US Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Twery, MJ (reprint author), NHLBI, Natl Ctr Sleep Disorders Res, Two Rockledge Ctr, Room 10181,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM twery@nih.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 1259 EP 1259 DI 10.1542/peds.2006-1433 PG 1 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100050 PM 16951023 ER PT J AU Shannon, MW Best, D Binns, HJ Forman, JA Johnson, CL Karr, CJ Kim, JJ Mazur, LJ Roberts, JR Rennels, MB Meissner, HC Baker, CJ Baltimore, RS Bocchini, JA Dennehy, PH Frenck, RW Hall, CB Long, SS McMillan, JA Powell, KR Rubin, LG Saari, TN AF Shannon, Michael W. Best, Dana Binns, Helen J. Forman, Joel A. Johnson, Christine L. Karr, Catherine J. Kim, Janice J. Mazur, Lynnette J. Roberts, James R. Rennels, Margaret B. Meissner, H. Cody Baker, Carol J. Baltimore, Robert S. Bocchini, Joseph A., Jr. Dennehy, Penelope H. Frenck, Robert W., Jr. Hall, Caroline B. Long, Sarah S. McMillan, Julia A. Powell, Keith R. Rubin, Lorry G. Saari, Thomas N. CA Comm Env Hlth Comm Infect Dis TI Chemical-biological terrorism and its impact on children SO PEDIATRICS LA English DT Article DE chemical terrorism; biological terrorism; emergency preparedness ID SUBWAY SARIN ATTACK; SMALLPOX-VACCINATION; SYNDROMIC SURVEILLANCE; PSYCHOSOCIAL IMPLICATIONS; EMERGENCY PHYSICIANS; GLYCOSIDASE ACTIVITY; DISASTER MANAGEMENT; SEPTEMBER 11TH; PEDIATRICIANS; BIOTERRORISM AB Children remain potential victims of chemical or biological terrorism. In recent years, children have even been specific targets of terrorist acts. Consequently, it is necessary to address the needs that children would face after a terrorist incident. A broad range of public health initiatives have occurred since September 11, 2001. Although the needs of children have been addressed in many of them, in many cases, these initiatives have been inadequate in ensuring the protection of children. In addition, public health and health care system preparedness for terrorism has been broadened to the so-called all-hazards approach, in which response plans for terrorism are blended with plans for a public health or health care system response to unintentional disasters (eg, natural events such as earthquakes or pandemic flu or manmade catastrophes such as a hazardous-materials spill). In response to new principles and programs that have appeared over the last 5 years, this policy statement provides an update of the 2000 policy statement. The roles of both the pediatrician and public health agencies continue to be emphasized; only a coordinated effort by pediatricians and public health can ensure that the needs of children, including emergency protocols in schools or child care centers, decontamination protocols, and mental health interventions, will be successful. C1 US EPA, Washington, DC 20460 USA. Ctr Dis Control & Prevent, Agcy Toxic Subst & Dis Registry, Atlanta, GA USA. NCI, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Shannon, MW (reprint author), US EPA, Washington, DC 20460 USA. OI Dennehy, Penelope/0000-0002-2259-5370 NR 52 TC 8 Z9 9 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP 1267 EP 1278 DI 10.1542/peds.2006-1700 PG 12 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100052 ER PT J AU Gafni, RI Hazra, R Maldarelli, F Tullio, AN DeCarlo, E Worrell, CJ Flaherty, JF Yale, K Kearney, BP Zeichner, SL AF Gafni, Rachel I. Hazra, Rohan Maldarelli, Frank Tullio, Antonella N. DeCarlo, Ellen Worrell, Carol J. Flaherty, John F. Yale, Kitty Kearney, Brian P. Zeichner, Steven L. TI Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: Impact on bone mineral density in HIV-infected children SO PEDIATRICS LA English DT Article DE bone mineral density; HIV; bone mineralization; antiretroviral therapies ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONKEYS MACACA-MULATTA; INFANT RHESUS MACAQUES; PUBERTAL CHANGES; METABOLISM; DENSITOMETRY; EFFICACY; PATTERN; SAFETY AB OBJECTIVE. Tenofovir disoproxil fumarate, a nucleotide analog HIV reverse transcriptase inhibitor with demonstrated activity against nucleoside-resistant HIV, is approved for use in adults but not children. Metabolic bone abnormalities have been seen in young animals given high-dose tenofovir and HIV-infected adults that were treated with oral tenofovir disoproxil fumarate. However, tenofovir disoproxil fumarate is being used in children despite a lack of bone safety data. We hypothesized that, given the higher rate of bone turnover that is associated with normal skeletal growth, the potential for TDF-related bone toxicity may be greater in children than in adults. METHODS. Fifteen highly antiretroviral-experienced HIV-infected children who were 8 to 16 years of age (mean +/- SD: 12 +/- 2) and required a change in therapy received tenofovir disoproxil fumarate 175 to 300 mg/m(2) per day (adult dose equivalent) as part of highly active antiretroviral therapy for up to 96 weeks. Bone mineral density of the lumbar spine, femoral neck, and total hip by dual-energy x-ray absorptiometry and blood and urine markers of bone metabolism were measured at 0, 24, 48, 72, and 96 weeks. RESULTS. Median z score (SD score compared with age, gender, and ethnicity-matched control subjects) of the lumbar spine, femoral neck, and total hip were decreased from baseline at 24 weeks and 48 weeks and then stabilized. Lumbar spine bone mineral apparent density (which estimates volumetric bone mineral density independent of bone size) z scores also decreased at 24 weeks. Absolute decreases in bone mineral density were observed in 6 children; the mean age of these children was significantly younger than the bone mineral density stable group (10.2 +/- 1.1 vs 13.2 +/- 1.8 years). The change in lumbar spine bone mineral density correlated with decreases in HIV plasma RNA during treatment. Metabolic markers of bone formation and resorption were variable. Two children in whom tenofovir disoproxil fumarate was discontinued because of bone loss that exceeded protocol allowances demonstrated partial or complete recovery of bone mineral density by 96 weeks. CONCLUSIONS. Tenofovir disoproxil fumarate use in children seems to be associated with decreases in bone mineral density that, in some children, stabilize after 24 weeks. Increases in bone markers and calcium excretion suggest that tenofovir disoproxil fumarate may stimulate bone resorption. Bone turnover is higher in children than in older adolescents and adults because of skeletal growth, potentially explaining the greater effect seen in young children. Decreases in bone mineral density correlate with decreases in viral load and young age, suggesting that young responders may be at greater risk for bone toxicity. C1 George Washington Univ, Childrens Natl Med Ctr, Sch Med,Div Canc & Immunol Res, Childrens Res Inst,Dept Pediat & Microbiol, Washington, DC 20010 USA. George Washington Univ, Childrens Natl Med Ctr, Sch Med,Div Canc & Immunol Res, Childrens Res Inst,Dept Immunol, Washington, DC 20010 USA. George Washington Univ, Childrens Natl Med Ctr, Sch Med,Div Canc & Immunol Res, Childrens Res Inst,Dept Trop Med, Washington, DC 20010 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Div Pediat Endocrinol, Dept Pediat, Baltimore, MD 21201 USA. Gilead Sci Inc, Foster City, CA 94404 USA. RP Zeichner, SL (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med,Div Canc & Immunol Res, Childrens Res Inst,Dept Pediat & Microbiol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM zeichner@gwu.edu FU Intramural NIH HHS NR 27 TC 91 Z9 96 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP E711 EP E718 DI 10.1542/peds.2005-2525 PG 8 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100098 PM 16923923 ER PT J AU Nader, PR O'Brien, M Houts, R Bradley, R Belsky, J Crosnoe, R Friedman, S Mei, ZG Susman, EJ AF Nader, Philip R. O'Brien, Marion Houts, Renate Bradley, Robert Belsky, Jay Crosnoe, Robert Friedman, Sarah Mei, Zuguo Susman, Elizabeth J. CA Natl Inst Child Hlth Human Dev TI Identifying risk for obesity in early childhood SO PEDIATRICS LA English DT Article DE BMI; childhood obesity; longitudinal growth ID ADOLESCENT OBESITY; FOLLOW-UP; OVERWEIGHT; CHILDREN; ADULTHOOD; LIFE; RECOMMENDATIONS; PREVALENCE AB OBJECTIVES. Our aim with this study was to assist clinicians by estimating the predictive value of earlier levels of BMI status on later risk of overweight and obesity during the middle childhood and early adolescent years. METHODS. We present growth data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, a longitudinal sample of 1042 healthy US children in 10 locations. Born in 1991, their growth reflects the secular trend of increasing overweight/obesity in the population. Height and weight of participating children in the study were measured at 7 time points. We examined odds ratios for overweight and obesity at age 12 years comparing the frequency with which children did versus did not reach specific BMI percentiles in the preschool- and elementary-age periods. To explore the question of whether and when earlier BMI was predictive of weight status at age 12 years, we used logistic regression to obtain the predicted probabilities of being overweight or obese (BMI >= 85%) at 12 years old on the basis of earlier BMI. RESULTS. Persistence of obesity is apparent for both the preschool and elementary school period. Children who were ever overweight (> 85th percentile), that is, >= 1 time at ages 24, 36, or 54 months during the preschool period were > 5 times as likely to be overweight at age 12 years than those who were below the 85th percentile for BMI at all 3 of the preschool ages. During the elementary school period, ages 7, 9, and 11 years, the more times a child was overweight, the greater the odds of being overweight at age 12 years relative to a child who was never overweight. Sixty percent of children who were overweight at any time during the preschool period and 80% of children who were overweight at any time during the elementary period were overweight at age 12 years. Follow-up calculations showed that 2 in 5 children whose BMIs were >= 50th percentile by age 3 years were overweight at age 12 years. No children who were < 50th percentile for BMI at all points during elementary school were overweight at age 12 years. Children who have higher range BMIs earlier, but not at the 85th percentile, are also more likely to be overweight at age 12 years. Even at time points before and including age 9 years, children whose BMIs are between the 75th and 85th percentile have an similar to 40% to 50% chance of being overweight at age 12 years. Children at 54 months old whose BMIs are between the 50th and 75th percentile are 4 times more likely to be overweight at age 12 years than their contemporaries who are < 50th percentile, and those whose BMIs are between the 75th and 85th percentile are > 6 times more likely to be overweight at age 12 years than those < 50th percentile. CONCLUSIONS. The data from this study indicate that children with BMIs > 85th percentile, as well as with BMIs in the high reference range are more likely than children whose BMI is < 50th percentile to continue to gain weight and reach overweight status by adolescence. Pediatricians can be confident in counseling parents to begin to address the at-risk child's eating and activity patterns rather than delaying in hopes that overweight and the patterns that support it will resolve themselves in due course. Identifying children at risk for adolescent obesity provides physicians with an opportunity for earlier intervention with the goal of limiting the progression of abnormal weight gain that results in the development of obesity-related morbidity. C1 NICHD, CRMC, Early Child Care & Youth Dev Res Network, CDB, Rockville, MD 20852 USA. Univ Calif San Diego, Div Community Pediat, San Diego, CA 92103 USA. Univ N Carolina, Dept Human Dev & Family Studies, Greensboro, NC 27412 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ Arkansas, Ctr Appl Studies Educ, Little Rock, AR 72204 USA. Univ London Birkbeck Coll, Inst Study Children Families & Social Issues, London WC1E 7HX, England. Univ Texas, Dept Sociol, Austin, TX 78712 USA. Univ Texas, Populat Res Ctr, Austin, TX 78712 USA. Ctr Dis Control & Prevent, Div Nutr & Phys Activ, Atlanta, GA USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. RP Nader, PR (reprint author), NICHD, CRMC, Early Child Care & Youth Dev Res Network, CDB, 6100 Execut Blvd,Suite 4B05, Rockville, MD 20852 USA. EM pnader@ucsd.edu OI Belsky, Jay/0000-0003-2191-2503 NR 31 TC 296 Z9 298 U1 6 U2 27 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP E594 EP E601 DI 10.1542/peds.2005-2801 PG 8 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100083 PM 16950951 ER PT J AU Prokhorov, AV Winickoff, JP Ahluwalia, JS Ossip-Klein, D Tanski, S Lando, HA Moolchan, ET Muramoto, M Klein, JD Weitzman, M Ford, KH AF Prokhorov, Alexander V. Winickoff, Jonathan P. Ahluwalia, Jasjit S. Ossip-Klein, Deborah Tanski, Susanne Lando, Harry A. Moolchan, Eric T. Muramoto, Myra Klein, Jonathan D. Weitzman, Michael Ford, Kentya H. CA Tobacco Consortium, Amer Acad Pedi TI Youth tobacco use: A global perspective for child health care clinicians SO PEDIATRICS LA English DT Review DE youth; smoking; tobacco ID FAGERSTROM TOLERANCE QUESTIONNAIRE; ADDRESSING PARENTAL SMOKING; WATER-PIPE SMOKING; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; ADOLESCENT SMOKERS; ADVISING PARENTS; MATERNAL SMOKING; BIDI CIGARETTES; STOP SMOKING AB Tobacco dependence, responsible for similar to 4 million annual deaths worldwide, is considered to be a "pediatric disease." The smoking epidemic is spreading rapidly in developing countries. Factors contributing to youth smoking in developing countries include cultural traditions, tobacco's easy accessibility and moderate pricing, peer and family influences, and tobacco companies' advertisements and promotional activities. Secondhand tobacco smoke exposure is a substantial problem that causes increased rates of pneumonia, otitis media, asthma, and other short- and long-term pediatric conditions. Parental tobacco use results in children's deprivation of essential needs such as nutrition and education. In this article we review contemporary evidence with respect to the etiology of nicotine dependence among youth, the forms of youth tobacco products worldwide, global youth tobacco-control efforts to date, medical education efforts, and child health care clinicians' special role in youth tobacco-control strategies. In addition, we provide a review of currently available funding opportunities for development and implementation of youth tobacco-control programs. C1 Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Massachusetts Gen Hosp, Gen Pediat Div, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Univ Kansas, Sch Med, Dept Prevent Med, Kansas City, KS 66103 USA. Univ Rochester, Sch Med, Dept Community & Prevent Med, Rochester, NY 14627 USA. Univ Rochester, Med Ctr, Dept Pediat, Ctr Child Hlth Res, Rochester, NY 14627 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Natl Inst Drug Abuse, Teen Tobacco Addict Treatment Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Arizona, Hlth Sci Ctr, Dept Family & Community Med, Tucson, AZ 85721 USA. Univ Rochester, Dept Pediat, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. Univ Rochester, Ctr Child Hlth Res, Dept Pediat, Rochester, NY 14627 USA. RP Prokhorov, AV (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, 1515 Holcombe Blvd,POB 301439, Houston, TX 77030 USA. EM aprokhor@mdanderson.org NR 130 TC 41 Z9 45 U1 3 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2006 VL 118 IS 3 BP E890 EP E903 DI 10.1542/peds.2005-0810 PG 14 WC Pediatrics SC Pediatrics GA 090NX UT WOS:000240959100118 PM 16950972 ER PT J AU Marczak, ED Ohinata, K Lipkowski, AW Yoshikawa, M AF Marczak, Ewa D. Ohinata, Kousaku Lipkowski, Andrzej W. Yoshikawa, Masaaki TI Arg-Ile-Tyr (RIY) derived from rapeseed protein decreases food intake and gastric emptying after oral administration in mice SO PEPTIDES LA English DT Article DE rapeseed; food intake; gastric emptying; CCK1 receptor ID CHOLECYSTOKININ; RAT; SECRETION; INTESTINE; PEPTIDES AB We previously reported that a bioactive tripeptide Arg-Ile-Tyr,(RIY), which has been isolated as an inhibitor for angiotensin I-converting enzyme from the subtilisin digest of rapeseed protein, decreased blood pressure. In this study, we also found that RIY dose-dependently decreased food intake at a dose of 150 mg/kg after oral administration in fasted ddY male mice. The anorexigenic action of RIY was blocked by a cholecystokinin-1 CCK1 receptor antagonist, lorglumide. RIY also decreased the gastric emptying rate at a dose of 150 mg/kg and the RIY-induced delay of gastric emptying was blocked by lorglumide. However, RIY had no affinity for CCK1 receptor. Taken together, RIY decreased food intake and gastric emptying by stimulating CCK release. (c) 2006 Elsevier Inc. All rights reserved. C1 Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Kyoto 6110011, Japan. NIEHS, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. Polish Acad Sci, Med Res Ctr, PL-02106 Warsaw, Poland. RP Yoshikawa, M (reprint author), Kyoto Univ, Grad Sch Agr, Div Food Sci & Biotechnol, Kyoto 6110011, Japan. EM yosikawa@kais.kyoto-u.ac.jp NR 15 TC 21 Z9 21 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD SEP PY 2006 VL 27 IS 9 BP 2065 EP 2068 DI 10.1016/j.peptides.2006.03.019 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 082IL UT WOS:000240379800003 PM 16647789 ER PT J AU Jozwiak, K Moaddel, R Yamaguchi, R Maciuk, A Wainer, IW AF Jozwiak, Krzysztof Moaddel, Ruin Yamaguchi, Rika Maciuk, Alexandre Wainer, Irving W. TI Non-competitive inhibitory activities of morphinan and morphine derivatives at the alpha 3 beta 4 neuronal nicotinic acetylcholine receptor determined using nonlinear chromatography and chemometric techniques SO PHARMACEUTICAL RESEARCH LA English DT Article DE affinity chromatography; functional assays; luminal binding site; molecular modeling; quinacrine binding site ID STATIONARY-PHASE; BINDING-SITES; DEXTROMETHORPHAN; AGONIST; TARGETS AB Purpose. A series of morphine and morphinan derivatives were chromatographed on a column containing immobilized cellular membranes from a cell line expressing the alpha 3 beta 4 neuronal nicotinic acetylcholine receptor (alpha 3 beta 4 nAChR). Methods. The results were analyzed using chemometric and molecular modeling techniques in order to predict the noncompetitive inhibitory (NCI) activity of these compounds, the molecular basis for the predicted activity and the binding sites of the inhibitors. Results. The data demonstrated that seven of seven morphinans were NCIs and bound in the central lumen of the nAChR while only 2 of 13 morphine derivatives had NCI activity and these compounds most likely bound at the quinacrine binding site on the nAChR. The predicted activities were confirmed using functional inhibition studies. Conclusions. The results indicate that this approach can be used to rapidly assess pharmacological activity and to guide new drug design. C1 NIA, Gerontol Res Ctr, NIH, Bioanalyt & Drug Discovery Unit, Baltimore, MD 21224 USA. Med Univ Lublin, Dept Chem, Lublin, Poland. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, Bioanalyt & Drug Discovery Unit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov NR 22 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD SEP PY 2006 VL 23 IS 9 BP 2175 EP 2182 DI 10.1007/s11095-006-9088-0 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 081IN UT WOS:000240310700024 PM 16952007 ER PT J AU Moslehi, R Chatterjee, N Church, TR Chen, J Yeager, M Weissfeld, J Hein, DW Hayes, RB AF Moslehi, Roxana Chatterjee, Nilanjan Church, Timothy R. Chen, Jinbo Yeager, Meredith Weissfeld, Joel Hein, David W. Hayes, Richard B. TI Cigarette smoking, N-acetyltransferase genes and the risk of advanced colorectal adenoma SO PHARMACOGENOMICS LA English DT Article DE cancer precursor; cigarette smoking; colorectal adenoma; N-acetyltransferases; NATI; NAT2 ID MOLECULAR-GENETICS; POLYADENYLATION POLYMORPHISM; CHROMOSOMAL LOCALIZATION; EPIDEMIOLOGIC EVIDENCE; METABOLIC-ACTIVATION; INCREASES RISK; NAT2 ALLOZYMES; CANCER-RISK; WILD-TYPE; N-ACETYLTRANSFERASE-1 AB Background: Cigarette use is associated with greater risk for colorectal adenoma, a colorectal cancer precursor. N-acetyltransf erases, NAT1 and NAT2, are important enzymes involved in the metabolism of aromatic amine carcinogens present in cigarette smoke. Our interest is in the polymorphisms within the NAT1 and NAT2 genes that influence the tobacco-colorectal tumor relationship by impacting on the metabolic activation and cletoxification of tobacco smoke-derived carcinogens. Methods: In the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, we compared NAT1 and NAT2 gene variant distributions for 772 cases with left-sided advanced adenoma and 777 gender and age-matched controls. Individual NAT1 and NAT2 diplotypes were assigned and NAT2 acetylator phenotypes were derived. Results: Risks for advanced colorectal adenoma were significantly increased among recent smokers (current smokers or those who quit less than 10 years ago) (odds ratio [OR] = 2.3, 95% confidence interval [Cl]: 1.7-3.1) and among those who smoked more than 20 cigarettes per day (OR = 1.7, 95% Cl: 1.3-2.2), compared with nonsmokers. Risk decreased with increasing NAT2 phenotypic activity (0: slow, 1: intermediate, and 2: rapid) (OR trend: 0.8; 95% Cl: 0.7-1.0, p-trend = 0.04) overall. When stratified by smoking status, significant phenotype-associated trends were observed among recent smokers (OR trend = 0.4, 95% Cl: 0.3-0.7, p trend < 0.001) (p-interaction = 0.02), but not among past or nonsmokers. Diplotypes most strongly associated with lower risks in smokers were NAT2*4/*5B (OR = 0.3, 95% Cl: 0.1-0.8, p = 0.01) and NAT2*4/*4 (OR = 0.2, 95% Cl: 0.04-0.7, p = 0.02), categorized as intermediate and rapid acetylators, respectively. One NAT1 diplotype, NAT1*4/*10 (OR = 0.5, 95% Cl: 0.3-0.9, p = 0.03), was also associated with a decreased risk in smokers. Conclusions: Our study indicated that NAT2 gene variants associated with a slow acetylator phenotype were more susceptible to the effects of tobacco smoking with respect to adenoma risk, providing leads for disease prevention. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Natl Canc Inst, Core Genotyping Facil, Ctr Adv Technol, Frederick, MD USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Moslehi, R (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8047, Rockville, MD 20852 USA. EM moslehir@mail.nih.gov RI Hein, David/A-9707-2008; OI Hayes, Richard/0000-0002-0918-661X; Church, Timothy R./0000-0003-3292-5035 FU Intramural NIH HHS; NCI NIH HHS [CA-34627, R01 CA034627, R01 CA034627-21] NR 38 TC 35 Z9 36 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD SEP PY 2006 VL 7 IS 6 BP 819 EP 829 DI 10.2217/14622416.7.6.819 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 091IH UT WOS:000241020000006 PM 16981843 ER PT J AU Alesci, S Manoli, I Michopoulos, VJ Brouwers, FM Le, H Gold, PW Blackman, MR Rennert, OM Su, YA Chrousos, GP AF Alesci, S. Manoli, I. Michopoulos, V. J. Brouwers, F. M. Le, H. Gold, P. W. Blackman, M. R. Rennert, O. M. Su, Y. A. Chrousos, G. P. TI Development of a human mitochondria-focused cDNA microarray (hMitChip) and validation in skeletal muscle cells: implications for pharmaco- and mitogenomics SO PHARMACOGENOMICS JOURNAL LA English DT Article DE mitochondria; microarray; glucocorticoid; skeletal muscle; myopathy; oxidative stress ID NUCLEAR GENE DEFECTS; MONOAMINE-OXIDASE-A; NEURODEGENERATIVE DISORDERS; CORTICOSTEROID MYOPATHY; TRANSCRIPTION FACTOR; HUMAN GENOME; EXPRESSION; PROTEIN; GLUCOCORTICOIDS; IDENTIFICATION AB Mitochondrial research has influenced our understanding of human evolution, physiology and pathophysiology. Mitochondria, intracellular organelles widely known as 'energy factories' of the cell, also play fundamental roles in intermediary metabolism, steroid hormone and heme biosyntheses, calcium signaling, generation of radical oxygen species, and apoptosis. Mitochondria possess a distinct DNA ( mitochondrial DNA); yet, the vast majority of mitochondrial proteins are encoded by the nuclear DNA. Mitochondria-related genetic defects have been described in a variety of mostly rare, often fatal, primary mitochondrial disorders; furthermore, they are increasingly reported in association with many common morbid conditions, such as cancer, obesity, diabetes and neurodegenerative disorders, although their role remains unclear. This study describes the creation of a human mitochondria-focused cDNA microarray (hMitChip) and its validation in human skeletal muscle cells treated with glucocorticoids. We suggest that hMitChip is a reliable and novel tool that will prove useful for systematically studying the contribution of mitochondrial genomics to human health and disease. C1 NIMH, CNE, NIH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NICCAM, Clin Invest Lab, NIH, Bethesda, MD USA. Univ Athens, Dept Pediat 1, Athens, Greece. NICHD, Lab Clin Genom, NIH, Bethesda, MD USA. Loyola Univ, Dept Pathol, Maywood, IL 60153 USA. RP Alesci, S (reprint author), NIMH, CNE, NIH, Clin Neuroendocrinol Branch, Bldg 10,Room 2D46,10 Ctr Dr,MSC-1284, Bethesda, MD 20892 USA. EM alescisa@mail.nih.gov RI Michopoulos, Vasiliki/C-7342-2014; OI Michopoulos, Vasiliki/0000-0003-2531-923X; Manoli, Irini/0000-0003-1543-2941 FU Intramural NIH HHS NR 65 TC 12 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD SEP-OCT PY 2006 VL 6 IS 5 BP 333 EP 342 DI 10.1038/sj.tpj.6500377 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 096NK UT WOS:000241383900006 PM 16534508 ER PT J AU Jamroziak, K Balcerczak, E Smolewski, P Robey, RW Cebula, B Panczyk, M Kowalczyk, M Szmigielska-Kaplon, A Mirowski, M Bates, SE Robak, T AF Jamroziak, Krzysztof Balcerczak, Ewa Smolewski, Piotr Robey, Robert W. Cebula, Barbara Panczyk, Mariusz Kowalczyk, Monika Szmigielska-Kaplon, Anna Mirowski, Marek Bates, Susan E. Robak, Tadeusz TI MDMR1 (ABCB1) gene poly m-orphism C3435T is associated with P-glycoprotein activity in B-cell chronic lymphocytic leukemia SO PHARMACOLOGICAL REPORTS LA English DT Article DE B-CLL; genetic susceptibility; MDR1; ABCB1; polymorphism; multidrug resistance ID TRANSPORTER MDR1 GENE; MULTIDRUG-RESISTANCE; PARKINSONS-DISEASE; POLISH POPULATION; ALLELIC VARIANTS; POLYMORPHISM; EXPRESSION; SUSCEPTIBILITY; CYCLOPHOSPHAMIDE; FLUDARABINE AB Functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the MDR1 (ABCB1) gene encoding the xenobiotic transporter P-glycoprotein (P-gp, MDR1, ABCB1) may influence susceptibility to several diseases as well as clinical outcome of treatment with P-gp substrates. Exposure to environmental chemicals is thought to be involved in the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) and P-gp-transported drugs are used in its treatment; however, little is known about the impact of the C3435T MDR1 SNP in B-CLL. In this study, I 10 Caucasian B-CLL patients and 201 healthy controls were genotyped for the MDR1 C3435T SNP. Additionally, P-gp activity was assessed in malignant lymphocytes of 22 untreated B-CLL patients. We observed a higher frequency of carriers of at least one 3435T allele (3435CT and 3435TT genotypes) among B-CLL patients as compared to normal individuals (76% vs. 63%, p = 0.027). The genotypes 3435CT and 3435TT were associated with B-CLL, (odds ratio = 1.8, 95% confidence interval = 1.1-3.0). Moreover, P-gp activity in B-CLL cells depended on MDR1 genotype, with the highest P-gp activity in 3435CC homozygotes, intermediate in 3435CT heterozygotes and the lowest in 3435TT homozygotes (p = 0.042). P-gp activity was also significantly lower in carriers of the T-allele (3435CT/TT genotype) as compared to the non-carriers (3435CC genotype), (p = 0.029). Taken together, these data indicate that the MDR1 C3435T SNP may carry an increased risk of developing B-CLL, possibly by virtue of decreased protection against P-gp-substrate carcinogens. The differences in P-gp activity in B-CLL tumor cells related to MDR1 genotype may have implications to the response to chemotherapy with P-gp transported anticancer agents. C1 Med Univ Lodz, Dept Hematol, PL-93510 Lodz, Poland. Med Univ Lodz, Mol Biol Lab, Dept Pharmaceut Biochem, PL-90151 Lodz, Poland. NCI, Dev Therapeut Dept, NIH, Bethesda, MD 20892 USA. RP Robak, T (reprint author), Med Univ Lodz, Dept Hematol, Ciolkowskiego 2, PL-93510 Lodz, Poland. EM robaktad@csk.umed.lodz.pl RI Szmigielska, Katarzyna/S-9216-2016; Balcerczak, Ewa/S-9838-2016 NR 44 TC 39 Z9 41 U1 1 U2 2 PU POLISH ACAD SCIENCES INST PHARMACOLOGY PI KRAKOW PA SMETNA 12, 31-343 KRAKOW, POLAND SN 1734-1140 J9 PHARMACOL REP JI Pharmacol. Rep. PD SEP-OCT PY 2006 VL 58 IS 5 BP 720 EP 728 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 102IP UT WOS:000241804500014 PM 17085864 ER PT J AU Abbracchio, MP Burnstock, G Boeynaems, JM Barnard, EA Boyer, JL Kennedy, C Knight, GE Fumagalli, M Gachet, C Jacobson, KA Weisman, GA AF Abbracchio, Maria P. Burnstock, Geoffrey Boeynaems, Jean-Marie Barnard, Eric A. Boyer, Jose L. Kennedy, Charles Knight, Gillian E. Fumagalli, Marta Gachet, Christian Jacobson, Kenneth A. Weisman, Gary A. TI International union of pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy SO PHARMACOLOGICAL REVIEWS LA English DT Review ID SMOOTH-MUSCLE-CELLS; TRANSMEMBRANE CONDUCTANCE REGULATOR; PLATELET ADP RECEPTOR; VASCULAR ENDOTHELIAL-CELLS; INDUCED ATP RELEASE; N-TYPE CA2+; RAT SYMPATHETIC NEURONS; GROWTH-FACTOR RECEPTOR; BETA-GAMMA-SUBUNITS; HUMAN MAST-CELLS AB There have been many advances in our knowledge about different aspects of P2Y receptor signaling since the last review published by our International Union of Pharmacology subcommittee. More receptor subtypes have been cloned and characterized and most orphan receptors deorphanized, so that it is now possible to provide a basis for a future subdivision of P2Y receptor subtypes. More is known about the functional elements of the P2Y receptor molecules and the signaling pathways involved, including interactions with ion channels. There have been substantial developments in the design of selective agonists and antagonists to some of the P2Y receptor subtypes. There are new findings about the mechanisms underlying nucleotide release and ectoenzymatic nucleotide breakdown. Interactions between P2Y receptors and receptors to other signaling molecules have been explored as well as P2Y-mediated control of gene transcription. The distribution and roles of P2Y receptor subtypes in many different cell types are better understood and P2Y receptor-related compounds are being explored for therapeutic purposes. These and other advances are discussed in the present review. C1 UCL Royal Free & Univ Coll Med Sch, Auton Neurosci Ctr, London NW3 2PF, England. Univ Milan, Dept Pharmacol Sci, Milan, Italy. Univ Libre Bruxelles, Erasme Hosp, Inst Rech Interdisciplinaire & Biol Humanie & Mol, Brussels, Belgium. Univ Libre Bruxelles, Erasme Hosp, Dept Med Chem, Brussels, Belgium. Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England. Inspire Pharmaceut Inc, Mol Pharmacol, Durham, NC USA. Univ Strathclyde, Dept Physiol & Pharmacol, Strathclyde, Scotland. Etabl Francais Sang Alsace, INSERM, U 311, Strasbourg, France. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Missouri, Dept Biochem, Columbia, MO USA. RP Burnstock, G (reprint author), UCL Royal Free & Univ Coll Med Sch, Auton Neurosci Ctr, Rowland Hill St, London NW3 2PF, England. EM g.burnstock@ucl.ac.uk RI Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014; Gachet, Christian/H-9156-2016; OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388; Fumagalli, Marta/0000-0002-0158-842X FU Intramural NIH HHS [Z01 DK031116-20]; NINDS NIH HHS [R01 NS050589] NR 603 TC 695 Z9 718 U1 7 U2 45 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD SEP PY 2006 VL 58 IS 3 BP 281 EP 341 DI 10.1124/pr.58.3.3 PG 61 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 083NW UT WOS:000240465500001 PM 16968944 ER PT J AU Pacher, P Batkai, S Kunos, G AF Pacher, Pal Batkai, Sandor Kunos, George TI The endocannabinoid system as an emerging target of pharmacotherapy SO PHARMACOLOGICAL REVIEWS LA English DT Review ID CANNABINOID CB1 RECEPTOR; ACID AMIDE HYDROLASE; TRAUMATIC BRAIN-INJURY; FOCAL CEREBRAL-ISCHEMIA; MESSENGER-RNA LEVELS; CLOSED-HEAD INJURY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; CONDITIONED PLACE PREFERENCE AB The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy. C1 NIAAA, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, NIH, Lab Physiol Studies, 5625 Fishers Lane,Room 2S-24, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z01 AA000375-02] NR 1334 TC 894 Z9 921 U1 27 U2 201 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD SEP PY 2006 VL 58 IS 3 BP 389 EP 462 DI 10.1124/pr.58.3.2 PG 74 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 083NW UT WOS:000240465500004 PM 16968947 ER PT J AU Winhusen, T Somoza, E Singal, BM Haffer, J Apparaju, S Mezinskis, J Desai, P Elkashef, A Chiang, CN Horn, P AF Winhusen, Theresa Somoza, Eugene Singal, Bonita M. Haffer, Judy Apparaju, Sandhya Mezinskis, Juris Desai, Pankaj Elkashef, Ahmed Chiang, C. Nora Horn, Paul TI Methylphenidate and cocaine: A placebo-controlled drug interaction study SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; methyphenidate; cardiovascular effects; subjective effects; cocaine pharmacokinetics ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DEPENDENT PATIENTS; MASS-SPECTROMETRY; DOUBLE-BLIND; ABUSERS; ADULTS; CHILDREN; PLASMA; ADHD AB Up to thirty percent of cocaine addicted individuals may meet diagnostic criteria for Aftention-Deficit/Hyperactivity Disorder (ADHD). Methylphenidate (MPH) is a highly effective and commonly used treatment for ADHD but, like cocaine, is a cardiovascular and central nervous system stimulant with the potential to cause toxicity at high doses. The present study was undertaken to investigate the likelihood of a toxic reaction in individuals who use cocaine while concurrently taking MPH. Seven non-treatment seeking cocaine-dependent individuals completed this placebo-controlled, crossover study with two factors: Medication (placebo, 60 mg MPH, 90 mg MPH) and Infusion (saline, 20 mg cocaine, 40 mg cocaine). Physiological measures included vital signs, adverse events, and electrocardiogram. Subjective response was measured with visual analog scale (VAS) ratings of craving and drug effect. Cocaine pharmacokinetic parameters were calculated for each participant at each drug combination, using a non-compartmental model. MPH was well tolerated, did not have a clinically significant impact on cocaine's physiological effects, and decreased some of the positive subjective effects of cocaine. MPH did not significantly alter the pharmacokinetics of cocaine. The study results suggest that MPH at the doses studied can likely be used safely in an outpatient setting with active cocaine users. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Vet Affairs Med Ctr, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Pharm, Cincinnati, OH 45267 USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Math, Cincinnati, OH 45221 USA. RP Winhusen, T (reprint author), Univ Cincinnati, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM winhusen@mdru.uc.edu OI Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [Y01 DA 50038-00] NR 28 TC 27 Z9 27 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 2006 VL 85 IS 1 BP 29 EP 38 DI 10.1016/j.pbb.2006.06.023 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 113ZH UT WOS:000242636000004 PM 16916538 ER PT J AU Heilig, M Egli, M AF Heilig, Markus Egli, Mark TI Pharmacological treatment of alcohol dependence: Target symptoms and target mechanisms SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE pharmacological treatment; alcohol dependence; target symptoms; target mechanisms ID CORTICOTROPIN-RELEASING-FACTOR; RANDOMIZED CONTROLLED-TRIAL; ANXIETY-LIKE BEHAVIOR; METABOTROPIC GLUTAMATE RECEPTORS; NEUROPEPTIDE-Y NPY; ETHANOL-SEEKING BEHAVIOR; PREFERRING P RATS; BIOLOGICALLY PREDISPOSED ALCOHOLICS; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; TESTING COMBINED PHARMACOTHERAPIES AB Alcoholism is a major public health problem and resembles, in many ways, other chronic relapsing medical conditions. At least 2 separate dimensions of its symptomatology offer targetable pathophysiological mechanisms. Systems that mediate positive reinforcement by alcohol are likely important targets in early stages of the disease, particularly in genetically susceptible individuals. In contrast, long term neuroadaptive changes caused by chronic alcohol use primarily appear to affect systems mediating negative affective states, and gain importance following a prolonged history of dependence. Feasibility of pharmacological treatment in alcoholism has been demonstrated by a first wave of drugs which consists of 3 currently approved medications, the aldehyde dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the functional glutamate antagonist acamprosate (ACM). The treatment toolkit is likely to be expanded in the near future. This will improve overall efficacy and allow individualized treatment, ultimately taking in account the patient's genetic makeup. In a second wave, early human efficacy data are available for the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the anticonvulsant topiramate. The third wave is comprised of compounds predicted to be effective based on a battery of animal models. Using such models, a short list of additional targets has accumulated sufficient preclinical validation to merit clinical development. These include the cannabinoid CBI receptor, receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors for stress-related neuropeptides corticotropin releasing factor (CRF), neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the field faces a major challenge to assure their delivery to patients. Published by Elsevier Inc. C1 NIAAA, DHHS, NIH, Bethesda, MD 20892 USA. RP Heilig, M (reprint author), NIAAA, DHHS, NIH, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov NR 218 TC 211 Z9 218 U1 8 U2 35 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD SEP PY 2006 VL 111 IS 3 BP 855 EP 876 DI 10.1016/j.pharmthera.2006.02.001 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075BD UT WOS:000239856100016 PM 16545872 ER PT J AU Horne, MK McCloskey, DJ Calis, K Wesley, R Childs, R Kasten-Sportes, C AF Horne, McDonald K., III McCloskey, Donna Jo Calis, Karim Wesley, Robert Childs, Richard Kasten-Sportes, Claude TI Use of heparin versus lepirudin flushes to prevent withdrawal occlusion of central venous access devices SO PHARMACOTHERAPY LA English DT Article DE lepirudin; heparin; venous access device; catheter function; withdrawal occlusion ID INDUCED THROMBOCYTOPENIA; CATHETERS; HIRUDIN; COMPLICATIONS; METAANALYSIS; TRIALS; APTT AB Study Objective. To determine whether lepirudin flushes are more effective than heparinized saline in preventing withdrawal occlusion of central venous access devices. Design. Randomized, double-blind clinical trial. Setting. Research institution-tertiary referral center. Patients. Forty-nine adults undergoing bone marrow transplantation for hematologic malignancies or metastatic solid tumors. Intervention. Twenty-four patients received heparin and 25 received lepirudin flushes. The heparin dose was 3 ml of porcine heparin 100 U/ml (300 U) per catheter lumen at least once/day; the lepirudin dose was 3 ml of lepirudin 100 mu g/ml (300 mu g) per catheter lumen at least once/day After 3-4 weeks, all 49 patients received the heparin flushes. Measurements and Main Results. Efficacy was assessed by the frequency with which the patients were treated with alteplase instillations for withdrawal occlusion of their central venous access devices during the first 4 months of catheterization. Three (12.5%) patients treated with heparin alone and five (20%) treated initially with lepirudin required afteplase instillations for an estimated relative risk with lepirudin versus heparin of 1.6 (95% confidence interval [CI] 0.40-13.86, p=0.70). Conclusion. Lepirudin was not more effective than heparin, which may have been related to the conservative dose of lepirudin administered. However, higher lepirudin doses are likely to incur an unacceptable risk of systemic anticoagulation. C1 NIH, Bethesda, MD 20892 USA. WG Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA. WG Magnuson Clin Ctr, Dept Pharm, Bethesda, MD USA. WG Magnuson Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Bldg 10,Room 2C306, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov FU Intramural NIH HHS NR 24 TC 14 Z9 14 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD SEP PY 2006 VL 26 IS 9 BP 1262 EP 1267 DI 10.1592/phco.26.9.1262 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 080XF UT WOS:000240281100007 PM 16945048 ER PT J AU Perry, JL Goldsmith, MR Williams, TR Radack, KP Christensen, T Gorham, J Pasquinelli, MA Toone, EJ Beratan, DN Simon, JD AF Perry, Jennifer L. Goldsmith, Michael R. Williams, T. Richard Radack, Kyle P. Christensen, Trine Gorham, Justin Pasquinelli, Melissa A. Toone, Eric J. Beratan, David N. Simon, John D. TI Binding of warfarin influences the acid-base equilibrium of H242 in sudlow site I of human serum albumin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID 2 LARGE FRAGMENTS; OCHRATOXIN-A; PROTEIN-BINDING; RECOMBINANT FRAGMENTS; DYNAMICS; ENERGY AB Sudlow Site I of human serum albumin (HSA) is located in subdomain IIA of the protein and serves as a binding cavity for a variety of ligands. In this study, the binding of warfarin (W) is examined using computational techniques and isothermal titration calorimetry (ITC). The structure of the docked warfarin anion (W-) to Site I is similar to that revealed by X-ray crystallography, with a calculated binding constant of 5.8 X 10(5) M-1. ITC experiments (pH 7.13 and I = 0.1) carried out in three different buffers (MOPs, phosphate and Tris) reveal binding of W- is accompanied by uptake of 0.30 +/- 0.02 protons from the solvent. This measurement suggests that the binding of W- is stabilized by an ion-pair interaction between protonated H242 and the phenoxide group of W-. C1 Duke Univ, Dept Chem, Durham, NC 27706 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Simon, JD (reprint author), Duke Univ, Dept Chem, Durham, NC 27706 USA. EM jsimon@duke.edu RI Beratan, David/C-5098-2011; OI Pasquinelli, Melissa/0000-0001-5815-2558 FU NIGMS NIH HHS [5T32-GM08487] NR 34 TC 19 Z9 19 U1 0 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2006 VL 82 IS 5 BP 1365 EP 1369 DI 10.1562/2006-02-23-RA-811 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 097DK UT WOS:000241426600029 PM 16563025 ER PT J AU Zheng, J Ma, BY Nussinov, R AF Zheng, Jie Ma, Buyong Nussinov, Ruth TI Consensus features in amyloid fibrils: sheet-sheet recognition via a (polar or nonpolar) zipper structure SO PHYSICAL BIOLOGY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; CROSS-BETA-SPINE; FORMING PEPTIDE; EARLY STEPS; AGGREGATION; KINETICS; OLIGOMERIZATION; CONFORMATIONS; STABILITIES; SEQUENCES AB Amyloid fibrils characterized as highly intractable thread-like species are associated with many neurodegenerative diseases. Although neither the mechanism of amyloid formation nor the origin of amyloid toxicity is currently completely understood, the detailed three-dimensional atomic structures of the yeast protein Sup35 and A beta amyloid protein determined by recent experiments provide the first and important step towards the comprehension of the pathogenesis and aggregation mechanisms of amyloid diseases. By analyzing these two amyloid peptides which have available crystal structures and other amyloid sequences with proposed structures using computational simulations, we delineate three common features in amyloid organizations and amyloid structures. These could contribute to an improved understanding of the molecular mechanism of amyloid formation, the nature of the aggregation driving forces that stabilize these structures and the development of potential therapeutic agents against amyloid diseases. C1 NCI, Basic Res Program, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Zheng, J (reprint author), NCI, Basic Res Program, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RI Ma, Buyong/F-9491-2011; Zheng, Jie/B-5057-2013 OI Ma, Buyong/0000-0002-7383-719X; Zheng, Jie/0000-0003-1547-3612 FU NCI NIH HHS [N01-CO-12400] NR 31 TC 27 Z9 27 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD SEP PY 2006 VL 3 IS 3 BP P1 EP P4 DI 10.1088/1478-3975/3/3/P01 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 111XT UT WOS:000242489900001 PM 17021379 ER PT J AU Tomic, S Vuletic, T Dolanski Babic, S Podgornik, R Krca, S Ivankovic, D Griparic, L Podgornik, R AF Tomic, S. Vuletic, T. Sanja, Dolanski Babic Podgornik, Rudi Krca, Sanja Ivankovic, Dusica Griparic, Lorena Podgornik, Rudi TI Screening and fundamental length scales in semidilute Na-DNA aqueous solutions SO PHYSICAL REVIEW LETTERS LA English DT Article ID POLYELECTROLYTE SOLUTIONS AB The fundamental length scales in semidilute Na-DNA aqueous solutions have been investigated by dielectric spectroscopy. The low- and the high-frequency relaxation modes are studied in detail. The length scale of the high-frequency relaxation mode at high DNA concentrations can be identified with the de Gennes-Pfeuty-Dobrynin correlation length of polyelectrolytes in semidilute solution, whereas at low DNA concentrations and in the low added salt limit the length scale shows an unusual exponent reminiscent of semidilute polyelectrolyte chains with hydrophobic backbone. The length scale of the low-frequency relaxation mode corresponds to a Gaussian chain composed of correlation blobs in the low added salt limit, and to the Odijk-Skolnick-Fixman value of the single chain persistence length in the high added salt limit. C1 Inst Fiz, Zagreb 10000, Croatia. Rudjer Boskovic Inst, Zagreb 10000, Croatia. Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. Univ Ljubljana, Dept Phys, Ljubljana 1000, Slovenia. Jozef Stefan Inst, Ljubljana 1000, Slovenia. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Zagreb, Sch Med, Dept Phys & Biophys, Zagreb 10000, Croatia. RP Tomic, S (reprint author), Inst Fiz, Zagreb 10000, Croatia. EM stomic@ifs.hr RI Tomic, Silvia/D-5466-2011; Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 18 TC 18 Z9 18 U1 2 U2 12 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD SEP 1 PY 2006 VL 97 IS 9 AR 098303 DI 10.1103/PhysRevLett.97.098303 PG 4 WC Physics, Multidisciplinary SC Physics GA 080HR UT WOS:000240239000066 PM 17026409 ER PT J AU Centlow, M Carcini, P Inman, J Larsson, J Brownstein, MJ Hansson, SR AF Centlow, M. Carcini, P. Inman, J. Larsson, J. Brownstein, M. J. Hansson, S. R. TI Placenta gene expression analysis of preeclampsia using a unique preeclampsia specific gene set. SO PLACENTA LA English DT Meeting Abstract CT 12th Meeting of the International-Federation-of-Placenta-Association CY SEP 06-09, 2006 CL Kobe, JAPAN SP Int Federat Placenta Assoc C1 Lund Univ, Dept Obstet & Gynecol, S-22100 Lund, Sweden. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD SEP-OCT PY 2006 VL 27 IS 9-10 BP A16 EP A16 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 081IX UT WOS:000240312200068 ER PT J AU Miller, RK Wilson, D Salafia, CM Ornoy, A Yacobi, S Richards, S Adair, D Lin, ZQ Plessinger, MA Polliotti, BM Hashem, M Asai, M Ozcan, T Woodall, A D'Gregorio, RP Camerio, M Malek, A Genbacev, O Mattison, DR Panigel, M AF Miller, R. K. Wilson, D. Salafia, C. M. Ornoy, A. Yacobi, S. Richards, S. Adair, D. Lin, Z. Q. Plessinger, M. A. Polliotti, B. M. Hashem, M. Asai, M. Ozcan, T. Woodall, A. D'Gregorio, R. Perez Camerio, M. Malek, A. Genbacev, O. Mattison, D. R. Panigel, M. TI Environmental impact on placental function in diseases of pregnancy SO PLACENTA LA English DT Meeting Abstract CT 12th Meeting of the International-Federation-of-Placenta-Association CY SEP 06-09, 2006 CL Kobe, JAPAN SP Int Federat Placenta Assoc C1 Univ Rochester, Rochester, NY USA. Columbia Univ, New York, NY USA. Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91010 Jerusalem, Israel. Univ Tennessee, Chattanooga, TN USA. So Illinois Univ, Edwardsville, IL 62026 USA. Aichi Med Univ, Nagoya, Aichi, Japan. Matern Hosp Concepcion Palacios, Caracas, Venezuela. Univ Bern, Bern, Switzerland. UCSF, San Francisco, CA USA. NIH, Bethesda, MD 20892 USA. U Paris VL, Paris, France. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD SEP-OCT PY 2006 VL 27 IS 9-10 BP A6 EP A6 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 081IX UT WOS:000240312200032 ER PT J AU Than, NG Magenheim, R Rahman, OA Nagy, B Hargitai, B Fule, T Sammar, M Szabo, G Hupuczi, P Sailer, I Kovalszk, I Bohn, H Mein, H Papp, Z AF Than, N. G. Magenheim, R. Rahman, O. A. Nagy, B. Hargitai, B. Fule, T. Sammar, M. Szabo, G. Hupuczi, P. Sailer, I. Kovalszk, I. Bohn, H. Mein, H. Papp, Z. TI Diagnostic value of placenta protein 13 (PP13) in the third trimester SO PLACENTA LA English DT Meeting Abstract CT 12th Meeting of the International-Federation-of-Placenta-Association CY SEP 06-09, 2006 CL Kobe, JAPAN SP Int Federat Placenta Assoc C1 Semmelweis Univ, Dept Obstet & Gynecol 1, Budapest, Hungary. Semmelweis Univ, Dept Pathol & Expt Canc Res 1, Budapest, Hungary. Wayne State Univ, Perinatol Res Branch, NICHD, NIH, Detroit, MI USA. Diagnost Technol Ltd, Haifa, Israel. Behringwerke AG, D-3550 Marburg, Germany. RI Nagy, Balint/F-6943-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD SEP-OCT PY 2006 VL 27 IS 9-10 BP A14 EP A14 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 081IX UT WOS:000240312200063 ER PT J AU Ferrari, PF Visalberghi, E Paukner, A Fogassi, L Ruggiero, A Suomi, SJ AF Ferrari, Pier F. Visalberghi, Elisabetta Paukner, Annika Fogassi, Leonardo Ruggiero, Angela Suomi, Stephen J. TI Neonatal imitation in rhesus macaques SO PLOS BIOLOGY LA English DT Article ID CHIMPANZEES PAN-TROGLODYTES; MACACA-NEMESTRINA; TONGUE PROTRUSION; FACIAL GESTURES; NEWBORN-INFANTS; PREMOTOR CORTEX; MIRROR NEURONS; MONKEYS; RECOGNITION; MECHANISMS AB The emergence of social behaviors early in life is likely crucial for the development of mother - infant relationships. Some of these behaviors, such as the capacity of neonates to imitate adult facial movements, were previously thought to be limited to humans and perhaps the ape lineage. Here we report the behavioral responses of infant rhesus macaques (Macaca mulatta) to the following human facial and hand gestures: lip smacking, tongue protrusion, mouth opening, hand opening, and opening and closing of eyes (control condition). In the third day of life, infant macaques imitate lip smacking and tongue protrusion. On the first day of life, the model's mouth openings elicited a similar matched behavior (lip smacking) in the infants. These imitative responses are present at an early stage of development, but they are apparently confined to a narrow temporal window. Because lip smacking is a core gesture in face-to-face interactions in macaques, neonatal imitation may serve to tune infants' affiliative responses to the social world. Our findings provide a quantitative description of neonatal imitation in a nonhuman primate species and suggest that these imitative capacities, contrary to what was previously thought, are not unique to the ape and human lineage. We suggest that their evolutionary origins may be traced to affiliative gestures with communicative functions. C1 Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy. Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. CNR, Ist Sci & Tecnol Cogniz, Rome, Italy. NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. Univ Parma, Dipartimento Psicol, I-43100 Parma, Italy. RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy. EM ferrari@biol.unipr.it OI Visalberghi, Elisabetta/0000-0001-7407-5468 NR 50 TC 151 Z9 155 U1 2 U2 23 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD SEP PY 2006 VL 4 IS 9 BP 1501 EP 1508 AR e302 DI 10.1371/journal.pbio.0040302 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 087KI UT WOS:000240740900002 PM 16953662 ER PT J AU Spencer, CCA Deloukas, P Hunt, S Mullikin, J Myers, S Silverman, BW Donnelly, P Bentley, D McVean, G AF Spencer, Chris C. A. Deloukas, Panos Hunt, Sarah Mullikin, Jim Myers, Simon Silverman, Bernard W. Donnelly, Peter Bentley, David McVean, Gil TI The influence of recombination on human genetic diversity SO PLOS GENETICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; HUMAN GENOME; PSEUDOAUTOSOMAL REGION; MEIOTIC RECOMBINATION; MAMMALIAN GENOMES; MUTATION-RATES; GC-CONTENT; EVOLUTION; SCALE; CONVERSION AB In humans, the rate of recombination, as measured on the megabase scale, is positively associated with the level of genetic variation, as measured at the genic scale. Despite considerable debate, it is not clear whether these factors are causally linked or, if they are, whether this is driven by the repeated action of adaptive evolution or molecular processes such as double-strand break formation and mismatch repair. We introduce three innovations to the analysis of recombination and diversity: fine-scale genetic maps estimated from genotype experiments that identify recombination hotspots at the kilobase scale, analysis of an entire human chromosome, and the use of wavelet techniques to identify correlations acting at different scales. We show that recombination influences genetic diversity only at the level of recombination hotspots. Hotspots are also associated with local increases in GC content and the relative frequency of GC-increasing mutations but have no effect on substitution rates. Broad-scale association between recombination and diversity is explained through covariance of both factors with base composition. To our knowledge, these results are the first evidence of a direct and local influence of recombination hotspots on genetic variation and the fate of individual mutations. However, that hotspots have no influence on substitution rates suggests that they are too ephemeral on an evolutionary time scale to have a strong influence on broader scale patterns of base composition and long-term molecular evolution. C1 Univ Oxford, Dept Stat, Oxford OX1 2JD, England. Wellcome Trust Sanger Inst, Hinxton, England. NHGRI, NIH, Bethesda, MD 20892 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Solexa Ltd, Saffron Walden, England. RP McVean, G (reprint author), Univ Oxford, Dept Stat, S Parks Rd, Oxford OX1 2JD, England. EM mcvean@stats.ox.ac.uk RI Silverman, Bernard/K-6417-2012; Deloukas, Panos/B-2922-2013; Myers, Simon/A-6792-2015; OI Silverman, Bernard/0000-0002-4059-2376; Deloukas, Panos/0000-0001-9251-070X; Myers, Simon/0000-0002-2585-9626; Hunt, Sarah/0000-0002-8350-1235 FU Wellcome Trust NR 54 TC 134 Z9 136 U1 0 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2006 VL 2 IS 9 BP 1375 EP 1385 AR e148 DI 10.1371/journal.pgen.0020148 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 089GF UT WOS:000240867700011 PM 17044736 ER PT J AU Jessop, L Rockmill, B Roeder, GS Lichten, M AF Jessop, Lea Rockmill, Beth Roeder, G. Shirleen Lichten, Michael TI Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of Sgs1 SO PLOS GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; RECOMBINATION INITIATION SITE; SACCHAROMYCES-CEREVISIAE; SYNAPTONEMAL COMPLEX; CROSSING-OVER; HOLLIDAY JUNCTIONS; BUDDING YEAST; KINASE CDC5; MEIOSIS-I; HELICASE AB Sgs1, the budding yeast homolog of the mammalian BLM helicase, has been implicated in preventing excess recombination during both vegetative growth and meiosis. Most meiotic crossover (CO) recombination requires full function of a set of yeast proteins (Zip1, Zip2, Zip3, Zip4/Spo22, Mer3, Msh4, and Msh5, termed the SIC or ZMM proteins) that are also required for homologous chromosome synapsis. We report here genetic and molecular assays showing that sgs1 single mutants display relatively modest increases in CO recombination (less than 1.6-fold relative to wild-type). In contrast, a much greater CO increase is seen when an sgs1 mutation is introduced into the CO- and synapsis-deficient zip1, zip2, zip3, mer3, or msh4 mutants (2- to 8-fold increase). Furthermore, close juxtaposition of the axes of homologous chromosomes is restored. CO restoration in the mutants is not accompanied by significant changes in noncrossover (NCO) recombinant frequencies. These findings show that Sgs1 has potent meiotic anti-CO activity, which is normally antagonized by SIC/ZMM proteins. Our data reinforce previous proposals for an early separation of meiotic processes that form CO and NCO recombinants. C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. Yale Univ, Dept Genet, New Haven, CT USA. Yale Univ, Howard Hughes Med Inst, New Haven, CT 06511 USA. RP Lichten, M (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. EM lichten@helix.nih.gov RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 FU Intramural NIH HHS NR 56 TC 97 Z9 99 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2006 VL 2 IS 9 BP 1402 EP 1412 AR e155 DI 10.1371/journal.pgen.0020155 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 089GF UT WOS:000240867700014 PM 17002499 ER PT J AU Suguitan, AL McAuliffe, J Mills, KL Jin, H Duke, G Lu, B Luke, CJ Murphy, B Swayne, DE Kemble, G Subbarao, K AF Suguitan, Amorsolo L., Jr. McAuliffe, Josephine Mills, Kimberly L. Jin, Hong Duke, Greg Lu, Bin Luke, Catherine J. Murphy, Brian Swayne, David E. Kemble, George Subbarao, Kanta TI Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets SO PLOS MEDICINE LA English DT Article ID COLD-ADAPTED INFLUENZA; AVIAN INFLUENZA; VIRUS-VACCINES; MF59-ADJUVANTED INFLUENZA; PANDEMIC INFLUENZA; REVERSE GENETICS; HONG-KONG; A/DUCK/SINGAPORE/97 VACCINE; TEMPERATURE SENSITIVITY; HEMAGGLUTININ CLEAVAGE AB Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin ( HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6) 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. MedImmune Vaccines, Mountain View, CA USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 187 Z9 200 U1 2 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD SEP PY 2006 VL 3 IS 9 BP 1541 EP 1555 AR e360 DI 10.1371/journal.pmed.0030360 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 103YT UT WOS:000241923800022 PM 16968127 ER PT J AU Longo, DL AF Longo, Dan L. TI Preoperative and postoperative chemotherapy improves outcome in gastric and esophagogastric junction adenocarcinoma SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 NIA, Bethesda, MD 20892 USA. RP Longo, DL (reprint author), NIA, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU JTE MULTIMEDIA PI BERWYN PA 1235 WESTLAKES DR, STE 220, BERWYN, PA 19312 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD SEP-OCT PY 2006 VL 119 IS 2 BP 54 EP 55 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA V44DS UT WOS:000202984000009 ER PT J AU Polozova, A Gionfriddo, E Salem, N AF Polozova, Alla Gionfriddo, Elisa Salem, Norman, Jr. TI Effect of docosahexaenoic acid on tissue targeting and metabolism of plasma lipoproteins SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 7th Fatty Acid and Cell Signaling Workshop CY SEP 28-30, 2005 CL Paris, FRANCE ID POLYUNSATURATED FATTY-ACIDS; LOW-DENSITY LIPOPROTEINS; LDL RECEPTOR ACTIVITY; BLOOD-BRAIN-BARRIER; APOLIPOPROTEIN-A-I; DIETARY FISH OIL; ARTERIAL PROTEOGLYCANS; CARDIOVASCULAR-DISEASE; CYNOMOLGUS MONKEYS; LIPID-COMPOSITION AB We examined the effect of the docosahexaenoic acid (DHA) content of lipoproteins on their metabolism in vivo by a radioisotope labeling and tracking method. Purified HDL and LDL were labeled with (3)H-cholesteryl oleate tracer. To mimic dietary-related changes in fatty acid composition of lipoproteins, we incorporated lipids acylated with either DHA, arachidonic (AA) or oleic (OA) acid to phosphatidylcholine (didocosahexaenoylphosphatidylcholine (di22:6-PC), diarachidonoylphosphatidylcholine (di20:4-PC) and dioleoylphosphatidylcholine (di18:0-PC), respectively) into the purified particles. The lipids, at the amount added, did not cause detectable alterations in the morphology of the lipoproteins. Levels of radiotracers in blood and in several target tissues such as brain, heart, liver, muscle and adipose were determined at 1.5, 3 and 24h after intravenous injection into C57BL/6J mice. No statistically significant differences were detected in the tissue distribution of tracers introduced into HDL enriched in DHA, compared to particles enriched with OA. In contrast, we found a significantly higher proportion of radiolabel associated with LDL enriched in DHA in heart, brown adipose and brain tissues. The uptake of labels associated with DHA containing LDL nearly doubled for heart and brown adipose tissues at 1.5 and 3 h, and it was 30% higher for brain tissues at 24 h. The tissue distribution of labels from the same particles enriched in AA or OA did not show a statistically significant difference from unaltered control lipoproteins. These findings point to the possible role of DHA in the regulation of LDL metabolism and involvement of the lipoproteins in transport of n-3 PUFA to target organs. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIAAA, LMBB, Bethesda, MD 20892 USA. RP Salem, N (reprint author), NIAAA, LMBB, 5625 Fishers Lane,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov NR 55 TC 21 Z9 21 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD SEP PY 2006 VL 75 IS 3 BP 183 EP 190 DI 10.1016/j.plefa.2006.05.009 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 086TW UT WOS:000240696900009 PM 16837179 ER PT J AU Nanda, NK Birch, L Greenberg, NM Prins, GS AF Nanda, Navreet K. Birch, Lynn Greenberg, Norman M. Prins, Gail S. TI MHC class I and class II molecules are expressed in both human and mouse prostate tumor microenvironment SO PROSTATE LA English DT Article DE HLA; immunotherapy; T cells ID MONOCLONAL-ANTIBODIES; ANTITUMOR RESPONSES; INTERFERON-GAMMA; TRANSGENIC MOUSE; W6/32 ANTIBODY; CANCER; ANTIGEN; RECOGNITION; TRANSPORT; DETERMINANTS AB BACKGROUND. There has been a determined search for therapies specifically aimed at eradicating tumor cells while leaving normal host cells unaffected. This goal can potentially be accomplished by engaging tumor antigen-specific T-cell repertoire to attack the tumor. A prerequisite for a successful T-cell-mediated attack against tumors or pathogens is that the target tissues express major histocompatibility complex (MHC) molecules. Using newer anti-MHC class I and MHC class II antibody reagents, we re-examined the expression of MHC in both human and mouse prostate tumors and their microenvironments. METHODS. Using immunocytochemistry, we examined the expression of MHC class I, class II, and CD3 molecules on cryopreserved human and mouse prostate tumor samples. RESULTS. MHC class I molecules are expressed by the entire spectrum of different stages of both human and mouse prostate tumor cells. Additionally, cells of the hematopoietic lineage, dispersed in the tumor microenvironment, showed significant expression of MHC class II molecules. Human prostate tumors also show a significant infiltrate of CD3(+) T cells. CONCLUSIONS. Expression of MHC class I and class II molecules within the prostate tumor microenvironment are consequential for T-cell-mediated immunotherapeutic approaches against prostate cancer. C1 Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC USA. Univ Illinois, Dept Urol, Chicago, IL USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Nanda, NK (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room 431,4 Ctr Dr,MSC 0420, Bethesda, MD 20892 USA. EM nandan@niaid.nih.gov FU NIDDK NIH HHS [R01 DK040890-17, DK-40890, R01 DK040890] NR 35 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 0270-4137 J9 PROSTATE JI Prostate PD SEP 1 PY 2006 VL 66 IS 12 BP 1275 EP 1284 DI 10.1002/pros.20432 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 073JP UT WOS:000239739300006 PM 16741922 ER PT J AU Park, SK Sakoda, LC Kang, D Chokkalingam, AP Lee, E Shin, HR Ahn, YO Shin, MH Lee, CW Lee, DH Blair, A Devesa, SS Hsing, AW AF Park, Sue Kyung Sakoda, Lori C. Kang, Daehee Chokkalingam, Anand P. Lee, Eunsik Shin, Hai-Rim Ahn, Yoon-Ok Shin, Myung-Hee Lee, Choong-Won Lee, Duk-Hee Blair, Aaron Devesa, Susan S. Hsing, Ann W. TI Rising prostate cancer rates in South Korea SO PROSTATE LA English DT Article DE prostate neoplasm; incidence; mortality; westernization; prostate-specific antigen; South Korea ID SRD5A2 GENE; UNITED-STATES; RISK; NUTRITION; COHORT; FRUIT AB BACKGROUND. Prostate cancer incidence and mortality rates in South Korea are relatively low, but rising steadily. METHODS. We examined age-standardized incidence and mortality trends of prostate cancer in South Korea to gain further insight into prostate cancer etiology. RESULTS. Although prostate cancer incidence has been low (7.9 per 100,000 man-years), it has increased up to 28.2% between 1996-1998 and 1999-2001. Prostate cancer mortality increased 12.7-fold over a 20-year period. Despite the increase in prostate cancer incidence and mortality rates, marked differences in rates remain for Koreans, Korean Americans, and Caucasian Americans. CONCLUSIONS. The rising rates of prostate cancer in South Korea cannot be attributed entirely to PSA screening due to the low PSA screening prevalence; this trend is most likely related to increased westernization among Koreans. Interdisciplinary epidemiological studies incorporating the collection of biological samples are needed to clarify the extent to which lifestyle and genetic factors contribute to the observed racial disparity. C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA USA. Seoul Natl Univ, Coll Med, Dept Urol, Seoul, South Korea. Korea Natl Canc Ctr, Res Inst Natl Canc Control & Evaluat, Goyang, South Korea. Sungkyunkwan Univ, Sch Med, Dept Social & Prevent Med, Suwon, South Korea. Keimyung Univ, Sch Med, Dept Prevent Med, Taegu, South Korea. Kyungpook Univ, Coll Med, Dept Prevent Med, Taegu, South Korea. RP Park, SK (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yeongeon Dong, Seoul 110799, South Korea. EM suepark@snu.ac.kr RI Kang, Dae Hee/E-8631-2012; Ahn, Yoon-Ok/J-5530-2012; Lee, Eunsik/J-5593-2012; Park, Sue Kyung/J-2757-2012 FU Intramural NIH HHS NR 36 TC 62 Z9 63 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP 1 PY 2006 VL 66 IS 12 BP 1285 EP 1291 DI 10.1002/pros.20419 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 073JP UT WOS:000239739300007 PM 16741923 ER PT J AU Pazgier, M Lubkowski, J AF Pazgier, Marzena Lubkowski, Jacek TI Expression and purification of recombinant human alpha-defensins in Escherichia coli SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE human alpha-defensins; expression; fusion protein; purification; antibacterial activity ID HIGH-LEVEL EXPRESSION; ANTIMICROBIAL CATIONIC PEPTIDES; MULTIPLE JOINED GENES; HUMAN BETA-DEFENSIN-2; HOST-DEFENSE; HUMAN-NEUTROPHILS; INNATE IMMUNITY; DISULFIDE ARRAY; PANETH CELLS; FUSION AB Different strategies have been developed to produce small antimicrobial peptides (AMPs) using recombinant techniques. Up to now, all efforts to obtain larger quantities of active recombinant human alpha-defensins have been only moderately successful. Here we report an effective method of biosynthesis of human alpha-defensins (hNP-1 to hNP-3 and hD-5 and hD-6) in the Escherichia coli. All the peptides, expressed as insoluble fusions with the peptide encoded by a portion of E. coli tryptophan operon (trp Delta LE 1413 polypeptide), were isolated from the inclusion bodies by immobilized metal affinity chromatography (IMAC) and separated from the fusion leader by chemical cleavage. Fully reduced peptides that were purified according to a straightforward protocol were subsequently folded, oxidized, and subjected to functional and structural analyses. With the exception of hD-6, all recombinant alpha-defensins exhibit expected anti-E. coli activity, as measured by the colony counting method. The method described in this report is a low-cost, efficient way of generating alpha-defensins in quantities ranging from milligrams to grams. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Mol Crystallog Lab, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Mol Crystallog Lab, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI Pazgier, Marzena/B-7295-2012 FU Intramural NIH HHS NR 69 TC 42 Z9 50 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD SEP PY 2006 VL 49 IS 1 BP 1 EP 8 DI 10.1016/j.pep.2006.05.004 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 085CJ UT WOS:000240580500001 PM 16839776 ER PT J AU Krepkiy, D Wong, K Gawrisch, K Yeliseev, A AF Krepkiy, Dmitriy Wong, Karen Gawrisch, Klaus Yeliseev, Alexel TI Bacterial expression of functional, biotinylated peripheral cannabinoid receptor CB2 SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE peripheral cannabinoid receptor CB2; biotinylation; GPCR; affinity purification; expression tag removal ID MALTOSE-BINDING PROTEIN; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI; HOLOENZYME SYNTHETASE; FUSION PROTEINS; IN-VIVO; PURIFICATION; NEUROTENSIN; SUBSTRATE; AVIDIN AB A biotin-protein ligase recognition site (BRS) was inserted into a polypeptide comprised of the maltose-binding protein, the peripheral cannabinoid receptor (CB2), thioredoxin A, and a polyhistidine tag at the carboxy terminus. Expression levels of the recombinant receptor in Escherichia coli BL21 (DE3) cells were similar to 1 mg per liter of bacterial culture. The biotinylated CB2-fusion fully retained its ligand-binding capacity. Introduction of the BRS at the C-terminus of the CB2 fusion protein (construct CB2-109) resulted in its complete in vivo biotinylation; the biotinylated protein was streptavidin-binding competent. Positioning of the BRS near the N-terminus of CB2 (CB2-112) resulted in a very low level of biotinylation in vivo. However, the detergent solubilized and purified CB2-112 fusion protein were successfully biotinylated in vitro by action of a BirA biotin-protein ligase. The biotinylated CB2-112 fusion protein was cleaved by the tobacco etch virus protease at specifically inserted sites, and deposited onto monomeric avidin agarose beads. Biotinylation of the recombinant CB2 receptor enabled not only purification but also immobilization of the GPCR on a solid support in homogeneous orientation which is beneficial for subsequent structural characterization. Published by Elsevier Inc. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Yeliseev, A (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM yeliseeva@mail.nih.gov RI Yeliseev, Alexei/B-3143-2009 FU Intramural NIH HHS NR 30 TC 23 Z9 23 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD SEP PY 2006 VL 49 IS 1 BP 60 EP 70 DI 10.1016/j.pep.2006.03.002 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 085CJ UT WOS:000240580500009 PM 16621595 ER PT J AU del Sol, A Fujihashi, H Amoros, D Nussinov, R AF del Sol, Antonio Fujihashi, Hirotomo Amoros, Dolors Nussinov, Ruth TI Residue centrality, functionally important residues, and active site shape: Analysis of enzyme and non-enzyme families SO PROTEIN SCIENCE LA English DT Article DE network; closeness centrality; characteristic path length; conserved central positions; active sites ID PROTEIN STRUCTURES; HIV-1 PROTEASE; RESISTANCE; MUTATIONS; SEQUENCES; NETWORKS; PATHWAYS; DYNAMICS; SURFACES; DATABASE AB The representation of protein structures as small-world networks facilitates the search for topological determinants, which may relate to functionally important residues. Here, we aimed to investigate the performance of residue centrality, viewed as a family fold characteristic, in identifying functionally important residues in protein families. Our study is based on 46 families, including 29 enzyme and 17 non-enzyme families. A total of 80% of these central positions corresponded to active site residues or residues in direct contact with these sites. For enzyme families, this percentage increased to 91%, while for non-enzyme families the percentage decreased substantially to 48%. A total of 70% of these central positions are located in catalytic sites in the enzyme families, 64% are in hetero-atom binding sites in those families binding hetero-atoms, and only 16% belong to protein -protein interfaces in families with protein -protein interaction data. These differences reflect the active site shape: enzyme active sites locate in surface clefts, hetero-atom binding residues are in deep cavities, while protein -protein interactions involve a more planar configuration. On the other hand, not all surface cavities or clefts are comprised of central residues. Thus, closeness centrality identifies functionally important residues in enzymes. While here we focus on binding sites, we expect to identify key residues for the integration and transmission of the information to the rest of the protein, reflecting the relationship between fold and function. Residue centrality is more conserved than the protein sequence, emphasizing the robustness of protein structures. C1 Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, Hachioji, Tokyo 1920031, Japan. SAIC Frederick Inc, Basic Res Program, Ctr Canc Res Nanobiol Program, NCI, Frederick, MD 21702 USA. Tel Aviv Univ, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP del Sol, A (reprint author), Fujirebio Inc, Div Res & Dev, Bioinformat Res Unit, 51 Komiya Cho, Hachioji, Tokyo 1920031, Japan. EM ao-mesa@fujirebio.co.jp FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 33 TC 65 Z9 66 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 2006 VL 15 IS 9 BP 2120 EP 2128 DI 10.1110/ps.062249106 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079DT UT WOS:000240156400009 PM 16882992 ER PT J AU Hamacher, M Apweiler, R Arnold, G Becker, A Bluggel, M Carrette, O Colvis, C Dunn, MJ Frohlich, T Fountoulakis, M van Hall, A Herberg, F Ji, J Kretzschmar, H Lewczuk, P Lubec, G Marcus, K Martens, L Bustamante, NP Park, YM Pennington, SR Robben, J Stuhler, K Reidegeld, KA Riederer, P Rossier, J Sanchez, JC Schrader, M Stephan, C Tagle, D Thiele, H Wang, J Wiltfang, J Yoo, JS Zhang, CG Klose, J Meyer, HE AF Hamacher, Michael Apweiler, Rolf Arnold, Georg Becker, Albert Blueggel, Martin Carrette, Odile Colvis, Christine Dunn, Michael J. Froehlich, Thomas Fountoulakis, Michael van Hall, Andre Herberg, Friedrich Ji, Juango Kretzschmar, Hans Lewczuk, Piotr Lubec, Gert Marcus, Katrin Martens, Lennart Bustamante, Nadine Palacios Park, Young Mok Pennington, Stephen R. Robben, Johan Stuehler, Kai Reidegeld, Kai A. Riederer, Peter Rossier, Jean Sanchez, Jean-Charles Schrader, Michael Stephan, Christian Tagle, Danilo Thiele, Herbert Wang, Jing Wiltfang, Jens Yoo, Jong Shin Zhang, Chenggang Klose, Joachim Meyer, Helmut E. TI HUPO Brain Proteome Project: Summary of the pilot phase and introduction of a comprehensive data reprocessing strategy SO PROTEOMICS LA English DT Editorial Material DE Brain Proteome Project; human; Human Proteome Organisation; mouse; pilot study ID IDENTIFICATIONS; PEPTIDE; GUIDELINES; EPILEPSY; PRIDE AB The Human Proteome Organisation (HUPO) initiated several projects focusing on the proteome analysis of distinct human organs. The Brain Proteome Project (BPP) is the initiative dedicated to the brain, its development and correlated diseases. Two pilot studies have been performed aiming at the comparison of techniques, laboratories and approaches. With the help of the results gained, objective data submission, storage and reprocessing workflow have been established. The biological relevance of the data will be drawn from the inter-laboratory comparisons as well as from the re-calculation of all data sets submitted by the different groups. in the following, results of the single groups as well as the centralised reprocessing effort will be summarised and compared, showing the added value of this concerted work. C1 Ruhr Univ Bochum, Med Proteom Ctr, D-44801 Bochum, Germany. European Bioinformat Inst, EMBL Outstn, Cambridge, England. Univ Munich, Gene Ctr, Lab Funct Genome Anal LAFUGA, Munich, Germany. Univ Klinikum Bonn, Inst Neuropathol, Bonn, Germany. Protagen AG, Dortmund, Germany. Univ Geneva, Fac Med, CMU, Biomed Prote Res Grp, Geneva, Switzerland. NIDA, Div Basic Neurosci & Behav Res, Bethesda, MD 20892 USA. Univ Coll Dublin, Conway Inst, Proteome Res Ctr, Dublin 2, Ireland. Acad Athens, Fdn Biomed Res, Div Biotechnol, GR-10673 Athens, Greece. Univ Kassel, Biochem Abt, Inst Biol, D-3500 Kassel, Germany. Peking Univ, Natl Lab Prot Engn & Plant Genet Engn, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China. Univ Munich, Zentrum Neuropathol & Prionforsch, Munich, Germany. Univ Erlangen Nurnberg, Klin & Poliklin Psychiat & Psychotherapie, Labor Mol Neurobiol, Poliklin & Inst Ambulanz, Erlangen, Germany. Med Univ Vienna, Dept Pediat, Div Neuroprot, Vienna, Austria. Univ Ghent, Fac Med & Hlth Sci, Dept Biochem, B-9000 Ghent, Belgium. Korea Basic Sci Inst, Taejon, South Korea. Univ Hasselt, Biomed Onderzoeksinst, Diepenbeek, Belgium. Univ Wurzburg, Dept Clin Neurochem, Clin & Policlin Psychiat & Psychotherapy, Wurzburg, Germany. Ecole Super Phys & Chim Ind Ville Paris, CNRS, UMR7637, Paris, France. Fachhsch Weihenstephan, Fachbereich Biotechnol, Freising Weihenstephan, Germany. RP Hamacher, M (reprint author), Ruhr Univ Bochum, Med Proteom Ctr, ZKF E-143,Univ Str 150, D-44801 Bochum, Germany. EM Michael.Hamacher@rub.de RI Zhang, Chenggang/B-1480-2009; Martens, Lennart/E-8816-2010; Becker, Albert/F-6248-2012; Herberg, Friedrich/B-5572-2015; Frohlich, Thomas/C-6735-2011; OI Wiltfang, Jens/0000-0003-1492-5330; Zhang, Chenggang/0000-0002-4521-3304; Lubec, Gert/0000-0002-6333-9461; Martens, Lennart/0000-0003-4277-658X; Herberg, Friedrich/0000-0001-7117-7653; Apweiler, Rolf/0000-0001-7078-200X NR 25 TC 42 Z9 42 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD SEP PY 2006 VL 6 IS 18 BP 4890 EP 4898 DI 10.1002/pmic.200600295 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 089JB UT WOS:000240875500002 PM 16927433 ER PT J AU Seneca, N Gulyas, B Varrone, A Schou, M Airaksinen, A Tauscher, J Vandenhende, F Kielbasa, W Farde, L Innis, RB Halldin, C AF Seneca, Nicholas Gulyas, Balazs Varrone, Andrea Schou, Magnus Airaksinen, Anu Tauscher, Johannes Vandenhende, Francois Kielbasa, William Farde, Lars Innis, Robert B. Halldin, Christer TI Atomoxetine occupies the norepinephrine transporter in a dose-dependent fashion: a PET study in nonhuman primate brain using (S,S)-[F-18]FMeNER-D-2 SO PSYCHOPHARMACOLOGY LA English DT Article DE atomoxetine; norepinephrine transporter occupancy; PET; nonhuman primate brain; (S,S)-[F-18]FMeNER-D-2 ID POSITRON-EMISSION-TOMOGRAPHY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; REBOXETINE ANALOGS; H-3 NISOXETINE; BINDING-SITES; RAT-BRAIN; AUTORADIOGRAPHY; MICE; RADIOTRACERS; RADIOLIGAND AB Rationale Atomoxetine is a potent and selective norepinephrine transporter (NET) reuptake inhibitor acting as a nonstimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Previous positron emission tomography (PET) studies had failed to demonstrate the feasibility of measuring a dose-dependent and saturable NET occupancy in human brain using [C-11]MeNER. Objective To determine if atomoxetine occupies NET in a dose-dependent fashion using (S,S)-[F-18]FMeNER-D-2 in nonhuman primate brain. Methods A total of eight PET measurements were performed in two cynomolgus monkeys. Each monkey was examined four times with PET: under baseline conditions and after steady-state infusion with 0.03, 0.06, or 0.12 mg/kg/h of atomoxetine. A prolonged intravenous (i.v.) infusion design was developed rather than an i.v. bolus to better mimic an oral absorption profile and to reach plasma steady state. Results During baseline conditions, (S,S)-[F-18]FMeNER-D-2 uptake was highest in the locus coeruleus, thalamus, mesencephalon, and the cingulate gyrus, whereas the radioactivity in the caudate was low. Peak equilibrium measurements were achieved using (S,S)-[F-18]FMeNER-D-2 in contrast to the previously reported data for [C-11]MeNER. After administration of atomoxetine, a dose-dependent occupancy from 38 to 82% was observed for various brain regions known to contain high densities of NET. Conclusions This is the first in vivo PET study to successfully demonstrate the ability to measure a dose-dependent change in NET occupancy in brain using (S,S)-[F-18]FMeNER-D-2. Furthermore, an asymptotic relationship between N-desmethylatomoxetine plasma concentration and NET occupancy was established. In total, these data encourage further PET studies using (S,S)-[F-18]FMeNER-D-2 in humans. C1 NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychol Sect, S-17176 Stockholm, Sweden. CNR, Biostruct & Bioimaging Inst, Naples, Italy. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Lilly Res Labs, Mont St Guibert, Belgium. RP Seneca, N (reprint author), NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. EM Nicholasseneca@mail.nih.gov RI Gulyas, Balazs/F-9508-2015; Tauscher, Johannes/M-5976-2016; Airaksinen, Anu/N-9070-2014 OI Airaksinen, Anu/0000-0002-5943-3105 FU Intramural NIH HHS NR 37 TC 53 Z9 56 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2006 VL 188 IS 1 BP 119 EP 127 DI 10.1007/s00213-006-0483-3 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 077HG UT WOS:000240019300013 PM 16896954 ER PT J AU Boyce-Rustay, JM Holmes, A AF Boyce-Rustay, Janel M. Holmes, Andrew TI Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit SO PSYCHOPHARMACOLOGY LA English DT Article DE NMDA receptor; NR2A KO; ethanol; sensitivity; rotarod; reward ID D-ASPARTATE ANTAGONISTS; LONG-TERM POTENTIATION; EPSILON-1 SUBUNIT; MOTOR INCOORDINATION; SENSITIVITY; RATS; DOPAMINE; SUBSTITUTION; ADAPTATIONS; CEREBELLUM AB Rationale The ionotropic NMDA glutamate receptor is composed of NR1 and NR2 (NR2A-D) subunits. While there is compelling evidence that NMDA receptors modulate behavioral effects of ethanol, there is little understanding of how the subunit composition of the NMDA receptor mediates these effects. Objectives In the current study, we assessed the relative roles of NMDA subunits via phenotypic assessment of ethanol-related behaviors in NR2A knockout (KO) mice. Results Results demonstrated that NR2A KO and heterozygous mice failed to show evidence of ethanol-induced conditioned place preference. As compared to wild-type (WT) controls, KO mice showed impaired motor coordination at baseline and, in some instances, following ethanol treatment on the accelerating rotarod, balance beam, and wire-hang tests. By contrast, open field locomotor-stimulant, sedative/hypnotic, and hypothermic responses to ethanol were not different between genotypes, nor was voluntary ethanol consumption and preference in a two-bottle choice paradigm. Blood ethanol concentrations were lower in KO than WT mice following intraperitoneal ethanol injection. Conclusions Results suggest that the loss of NR2A subunit-containing NMDA receptors impairs the ability to form or express learned reward-related responses to ethanol and causes deficits in motor coordination. However, the loss of NR2A does not alter other measures of acute ethanol intoxication or ethanol consumption, possibly implicating other NMDA subunits in these effects. These data provide novel insight into the role of NMDA receptors in modulating the behavioral effects of ethanol. C1 Abbott Labs, Abbott Pk, IL 60064 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Boyce-Rustay, JM (reprint author), Abbott Labs, R4CY 13A-2,100 Abbott Pk Rd, Abbott Pk, IL 60064 USA. EM janel.boyce-rustay@abbott.com NR 44 TC 41 Z9 41 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2006 VL 187 IS 4 BP 455 EP 466 DI 10.1007/s00213-006-0448-6 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 072IE UT WOS:000239666300007 PM 16835771 ER PT J AU Cornwell, BR Echiverri, AM Grillon, C AF Cornwell, Brian R. Echiverri, Aileen M. Grillon, Christian TI Attentional blink and prepulse inhibition of startle are positively correlated SO PSYCHOPHYSIOLOGY LA English DT Article DE attentional blink; prepulse inhibition; startle reflex; inhibitory processes; attention ID PERCEPTUAL PROCESSING DEMANDS; SERIAL VISUAL PRESENTATION; EYEBLINK MODIFICATION; OBJECT SUBSTITUTION; BACKWARD-MASKING; SCHIZOPHRENIA; REFLEX; CONSOLIDATION; HABITUATION; SUPPRESSION AB Although a link between the attentional blink and prepulse startle inhibition has been considered, no evidence of this relationship has been reported. We delivered acoustic startle probes during rapid serial visual presentations in which the relative positions of two targets (targets 1 and 2) was varied within a stream of distractors. Startle probes were presented at 100 ms lead intervals relative to onset of a target or distractor. We found positive correlations between visual prepulse inhibition and attentional blink effects across participants. As the magnitude of prepulse inhibition with target and distractor lead stimuli increased, deficits in identifying target 2 during the attentional blink increased, suggesting similar processes underlying these phenomena. Whereas prepulse inhibition may reveal the strength of inhibition to protect stimulus processing, attentional blink may index the rate of recovery from similar inhibitory processes. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Cornwell, BR (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM cornwellb@mail.nih.gov FU Intramural NIH HHS NR 46 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2006 VL 43 IS 5 BP 504 EP 510 DI 10.1111/j.1469-8986.2006.00421.x PG 7 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 082EB UT WOS:000240368400011 PM 16965613 ER PT J AU Davidson, KW Kupfer, DJ Bigger, JT Califf, RM Carney, RM Coyne, JC Czajkowski, SM Frank, E Frasure-Smith, N Freedland, KE Froelicher, ES Glassman, AH Katon, WL Kaufmann, PG Kessler, RC Kraemer, HC Krishnan, KRR Lesperance, F Rieckmann, N Sheps, DS Suls, JM AF Davidson, Karina W. Kupfer, David J. Bigger, J. Thomas Califf, Robert M. Carney, Robert M. Coyne, James C. Czajkowski, Susan M. Frank, Ellen Frasure-Smith, Nancy Freedland, Kenneth E. Froelicher, Erika S. Glassman, Alexander H. Katon, Wayne L. Kaufmann, Peter G. Kessler, Ronald C. Kraemer, Helena C. Krishnan, K. Ranga R. Lesperance, Francois Rieckmann, Nina Sheps, David S. Suls, Jerry M. TI Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute working group report SO PSYCHOSOMATIC MEDICINE LA English DT Article DE depression; cardiovascular diseases; assessment; treatment; consensus; recommendations ID MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; PLATELET/ENDOTHELIAL BIOMARKERS; ENHANCING RECOVERY; COLLABORATIVE CARE; UNITED-STATES; SERTRALINE; EVENTS; COMORBIDITY; SENSITIVITY AB Objective: The National Heart, Lung, and Blood Institute convened an interdisciplinary working group of experts to develop recommendations for the assessment and treatment of depression in patients with coronary heart disease (CHD). Method: Consensus of experts. Results: Our current recommendations are that the Beck Depression Inventory-I be employed for epidemiological studies of depression and CHD, that the Patient Health Questionnaire 2-item version be employed for screening for trial eligibility, that the Depression Interview and Structured Hamilton (DISH) be employed for diagnostic ascertainment for trial inclusion, and that the Hamilton rating scale, which is part of the DISH, be employed for both depression symptom reduction and the remission criterion in any trial. We further recommend that a randomized controlled trial be undertaken to determine whether selective serotonin reuptake inhibitors, psychotherapy, or combined treatment can reduce the risk of CHD events and mortality associated with depression in CHD patients. Conclusions: This report summarizes the recommendations made by the working group and discusses the rationale for each recommendation, the strengths and weaknesses of alternative approaches to assessment and treatment, and the implications for future research in this area. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Mt Sinai Sch Med, Cardiovasc Inst, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst, Dept Psychiat, Pittsburgh, PA 15260 USA. NHLBI, Behav Med & Prevent Res Grp, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Clin Res Inst, Durham, NC 27706 USA. Washington Univ, Sch Med, Behav Med Ctr, Dept Psychiat, St Louis, MO 63130 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. McGill Univ, Dept Psychiat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Sch Nursing, Montreal, PQ H3A 2T5, Canada. Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. Univ Montreal, Ctr Hosp, Res Ctr, Montreal, PQ H3C 3J7, Canada. Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. Univ Florida, Div Cardiovasc Med, Gainesville, FL 32611 USA. Malcom Randall VA Med Ctr, Gainesville, FL USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Davidson, KW (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 622 W 168th St,PH9 Ctr,Room 941, New York, NY 10032 USA. EM kd2124@columbia.edu RI Lesperance, Francois/C-4716-2015 OI Lesperance, Francois/0000-0003-4604-2823 NR 25 TC 108 Z9 111 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 2006 VL 68 IS 5 BP 645 EP 650 DI 10.1097/01.psy.0000233233.48738.22 PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 093YH UT WOS:000241205700001 PM 17012516 ER PT J AU Coryell, W Dindo, L Fyer, A Pine, DS AF Coryell, William Dindo, Lilian Fyer, Abby Pine, Daniel S. TI Onset of spontaneous panic attacks: A prospective study of risk factors SO PSYCHOSOMATIC MEDICINE LA English DT Article DE panic disorder; carbon dioxide; trait marker; follow-up; neuroticism ID 35-PERCENT CO2 CHALLENGE; CARBON-DIOXIDE; ANXIETY DISORDERS; HYPERSENSITIVITY; SENSITIVITY; ADOLESCENTS; INHALATION; RELATIVES; CHILDREN; MARKER AB Objective: Earlier analyses have shown that, among currently well individuals with no history of panic attacks, a family history of panic disorder is associated with a greater likelihood of panic symptoms after exposure to 35% CO2 and of ventilatory-response abnormalities during inhalation of 5% CO2 An association of those features with a subsequent onset of panic attacks would compose additional evidence that they are trait markers for panic disorder. Methods: Subjects who were free of current Axis I disorders other than simple or social phobia and who had a first-degree relative with panic disorder (high risk) and subjects who had no first-degree relatives with panic disorder or major depressive disorder (low-risk) underwent two challenge procedures. The first measured anxiety responses to a single breath of 35% CO2, and the second measured ventilatory responses to a 3-minute exposure to 5% CO2. After a mean interval of 4 years, 66 high-risk (48 female; mean age = 23.0 years) and 24 low-risk subjects (15 female; mean age = 23.1 years) were questioned by telephone about the occurrence of any spontaneous panic attack in the interval. Results: Sixteen (23.9%) of the high-risk and one (4.2%) of low-risk subjects had experienced at least one spontaneous panic attack; Cox regression analyses revealed a significant relationship between abnormal ventilatory responses to 5% CO2 and the later onset of panic attacks. Subjective responses to 35% CO2 were not predictive. Neuroticism scores were not associated with abnormal ventilatory responses to CO2 but were also predictive of later panic attacks. Conclusions: High neuroticism scores and abnormal ventilatory responses to 5% CO2 appear to be additive trait markers for panic disorder. C1 Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. Columbia Univ, Sch Med, New York, NY 10027 USA. NIMH, Bethesda, MD 20892 USA. RP Coryell, W (reprint author), Univ Iowa, Carver Coll Med, Dept Psychiat, 2-205 MEB, Iowa City, IA 52242 USA. EM william-coryell@uiowa.edu FU NIMH NIH HHS [R01-MH56132] NR 28 TC 11 Z9 11 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 2006 VL 68 IS 5 BP 754 EP 757 DI 10.1097/01.psy.0000232268.00327.b4 PG 4 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 093YH UT WOS:000241205700016 PM 17012529 ER PT J AU O'Fallon, LR AF O'Fallon, Liam R. TI Fostering the relationship between environmental health and nursing SO PUBLIC HEALTH NURSING LA English DT Editorial Material C1 Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. RP O'Fallon, LR (reprint author), Natl Inst Environm Hlth Sci, Div Extramural Res & Training, POB 12233,MD EC-21, Res Triangle Pk, NC 27709 USA. EM ofallon@niehs.nih.gov NR 10 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD SEP-OCT PY 2006 VL 23 IS 5 BP 377 EP 380 DI 10.1111/j.1525-1446.2006.00576.x PG 4 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 081LQ UT WOS:000240319500001 PM 16961557 ER PT J AU Backus, ASN Hewitt, JB Chalupka, SM AF Backus, Ann S. N. Hewitt, Jeanne Beauchamp Chalupka, Stephanie M. TI Using a site visit to a contaminated location as a focus for environmental health education for academic and public health nurses SO PUBLIC HEALTH NURSING LA English DT Article; Proceedings Paper CT 130th Annual Meeting of the American-Public-Health-Association CY NOV 09-13, 2002 CL PHILADELPHIA, PA SP Amer Public Hlth Assoc DE community case study; competencies; environmental health nursing education; environmental health; Institute of Medicine competencies; nursing faculty; public health nursing education ID NURSING-EDUCATION; MASSACHUSETTS; WOBURN; WATER AB We describe a conference initiative that is distinguished by the use of a "community case study" to increase the knowledge and skills of nursing faculty and public health nurses in environmental health and to provide networking support to facilitate infusion of environmental health into nursing curricula and public health nursing practice. The Institute of Medicine's (1995) general environmental health competencies for nurses provided the conference framework. Woburn, Massachusetts, a Superfund site, served as the community case study to illustrate a complex environmental health problem. Over an extended period of time, Woburn was contaminated with multiple chemicals that eventually contaminated the drinking water supply; a cluster of childhood leukemia cases was linked subsequently to the Superfund site contaminants. A 6-hr interpreted walking and bus tour of the Superfund site enabled us to visit the premises of responsible parties, the vapor extraction fields, the capped Well H in the wooded wetlands, and to tour the affected neighborhood. This intensive, hands-on approach to learning environmental health content and skills that incorporated multiple learning strategies serves as a model for developing future conferences for public health nurses and nursing faculty. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Outreach Community Outreach & Educ Program,NIEHS, Boston, MA 02115 USA. Univ Wisconsin, Community Outreach & Educ Programs, Milwaukee, WI 53201 USA. Univ Massachusetts, Sch Hlth & Environm, Lowell, MA USA. RP Backus, ASN (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Outreach Community Outreach & Educ Program,NIEHS, Room 1-1402,665 Huntington Ave, Boston, MA 02115 USA. EM abackus@hohp.harvard.edu FU NIEHS NIH HHS [P30 ES004184, P30 ES000002] NR 42 TC 4 Z9 4 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0737-1209 J9 PUBLIC HEALTH NURS JI Public Health Nurs. PD SEP-OCT PY 2006 VL 23 IS 5 BP 410 EP 432 DI 10.1111/j.1525-1446.2006.00580.x PG 23 WC Public, Environmental & Occupational Health; Nursing SC Public, Environmental & Occupational Health; Nursing GA 081LQ UT WOS:000240319500005 PM 16961561 ER PT J AU Justus, BL Falkenstein, P Huston, AL Plazas, MC Ning, H Miller, RW AF Justus, Brian L. Falkenstein, Paul Huston, Alan L. Plazas, Maria C. Ning, Holly Miller, Robert W. TI Elimination of Cerenkov interference in a fibre-optic-coupled radiation dosemeter SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID PLASTIC SCINTILLATION DOSIMETRY; LUMINESCENCE DOSIMETRY; LIGHT AB An optical fibre point dosemeter based on the gated detection of the luminescence from a Cu1+-doped fused quartz detector effectively eliminated errors due to Cerenkov radiation and native fibre fluorescence. The gated optical fibre dosemeter overcomes serious problems faced by scintillation and optically stimulated luminescence approaches to optical fibre point dosimetry. The dosemeter was tested using an external beam radiotherapy machine that provided pulses of 6 MV X rays. Gated detection was used to discriminate the signal collected during the radiation pulses, which included contributions from Cerenkov radiation and native fibre fluorescence, from the signal collected between the radiation pulses, which contained only the long-lived luminescence from the Cu1+-doped fused quartz detector. Gated detection of the luminescence provided accurate, real-time dose measurements that were linear with absorbed dose, independent of dose rate and that were accurate for all field sizes studied. C1 USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20784 USA. Univ Nacl Colombia, Bogota, Colombia. RP Justus, BL (reprint author), USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. EM justus@nrl.navy.mil NR 9 TC 10 Z9 10 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD SEP PY 2006 VL 120 IS 1-4 BP 20 EP 23 DI 10.1093/rpd/nci525 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 086RZ UT WOS:000240692000004 PM 16717108 ER PT J AU Sholom, S Chumak, V Desrosiers, M Bouville, A AF Sholom, S. Chumak, V. Desrosiers, M. Bouville, A. TI A transferability study of the EPR-tooth-dosimetry technique SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID ELECTRON-PARAMAGNETIC-RESONANCE; ENAMEL AB The transferability of a measurement protocol from one laboratory to another is an important feature of any mature, standardised protocol. The electron paramagnetic resonance (EPR)-tooth dosimetry technique that was developed in Scientific Center for Radiation Medicine, AMS, Ukraine (SCRM) for routine dosimetry of Chernobyl liquidators has demonstrated consistent results in several inter-laboratory measurement comparisons. Transferability to the EPR dosimetry laboratory at the National Institute of Standards and Technology (NIST) was examined. Several approaches were used to test the technique, including dose reconstruction of SCRM-NIST inter-comparison samples. The study has demonstrated full transferability of the technique and the possibility to reproduce results in a different laboratory environment. C1 Sci Ctr Radiat Med, Kiev, Ukraine. Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA. RP Sholom, S (reprint author), Sci Ctr Radiat Med, Melnikova St,53, Kiev, Ukraine. EM sergey_sholom@yahoo.com RI Chumak, Vadim/N-6960-2015 OI Chumak, Vadim/0000-0001-6045-9356 NR 11 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD SEP PY 2006 VL 120 IS 1-4 BP 210 EP 215 DI 10.1093/rpd/nci678 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 086RZ UT WOS:000240692000044 PM 16731688 ER PT J AU Skopec, M Loew, M Price, JL Guardala, N Moscovitch, M AF Skopec, M. Loew, M. Price, J. L. Guardala, N. Moscovitch, M. TI Discrimination of photon from proton irradiation using glow curve feature extraction and vector analysis SO RADIATION PROTECTION DOSIMETRY LA English DT Article AB Two types of thermoluminescence dosemeters (TLDs), the Harshaw LiF:Mg,Ti (TLD-100) and CaF2:Tm (TLD-300) were investigated for their glow curve response to separate photon and proton irradiations. The TLDs were exposed to gamma irradiation from a Cs-137 source and proton irradiation using a positive ion accelerator. The glow curve peak structure for each individual TLD exposure was deconvolved to obtain peak height, width, and position. Simulated mixed-field glow curves were obtained by superposition of the experimentally obtained single field exposures. Feature vectors were composed of two kinds of features: those from deconvolution and those taken in the neighbourhood of several glow curve peaks. The inner product of the feature vectors was used to discriminate among the pure photon, pure proton and simulated mixed-field irradiations. In the pure cases, identification of radiation types is both straightforward and effective. Mixed-field discrimination did not succeed using deconvolution features, but the peak-neighbourhood features proved to discriminate reliably. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. USN, Ctr Surface Warfare, Carderock Div, Bethesda, MD USA. Georgetown Univ, Washington, DC USA. RP Skopec, M (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM marskopec@yahoo.com NR 3 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD SEP PY 2006 VL 120 IS 1-4 BP 268 EP 272 DI 10.1093/rpd/nci533 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 086RZ UT WOS:000240692000055 PM 16614091 ER PT J AU Glaser, V AF Glaser, Vicki TI National Institute on Aging SO REJUVENATION RESEARCH LA English DT Editorial Material C1 NIA, Res Program, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1549-1684 J9 REJUV RES JI Rejuv. Res. PD FAL PY 2006 VL 9 IS 3 BP 419 EP 422 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 074TN UT WOS:000239834800009 ER PT J AU Falco, G Stanghellini, I Ko, MSH AF Falco, Geppino Stanghellini, Ilaria Ko, Minoru S. H. TI Use of Chuk as an internal standard suitable for quantitative RT-PCR in mouse preimplantation embryos SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article DE gene expression; internal standard; mouse preimplantation; normalization; Q-PCR ID GENE-EXPRESSION AB Analysis of gene expression changes during preimplantation development by quantitative reverse transcription-polymerase chain reaction (Q-PCR) requires appropriate internal standards. Ideally, such a gene should show a constant level of transcripts per embryo across all preimplantation stages from unfertilized eggs to blastocysts. By analysing the microarray-based gene expression profiles of preimplantation embryos, it was found that a conserved helix-loop-helix ubiquitous kinase gene (Chuk, also known as I kappa B kinase alpha, IKK alpha or IKK1) satisfied this criterion. To test the utility of this gene as an internal standard for Q-PCR, the expression levels of two known genes (Nalp5/Mater, Pou5f1/Oct3/Oct4) were normalized by Chuk and other housekeeping genes (Actb, Gapdh, Eef1a1, and H2afz) and demonstrated that the former was more consistent with the expression patterns obtained by a whole-mount in-situ hybridization than those reported previously with the latter. It is concluded that Chuk, unlike other commonly used normalization controls, is a reliable and suitable internal standard for measuring gene expression levels by Q-PCR in mouse oocytes and preimplantation embryos. C1 NIA, Dev Genom & Ageing Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Ageing Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM KoM@mail.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS NR 19 TC 10 Z9 10 U1 0 U2 0 PU REPRODUCTIVE HEALTHCARE LTD PI CAMBRIDGE PA DUCK END FARM, DRY DRAYTON, CAMBRIDGE, CB3 8DB, ENGLAND SN 1472-6483 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD SEP PY 2006 VL 13 IS 3 BP 394 EP 403 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 082QE UT WOS:000240401000021 PM 16984773 ER PT J AU Renesto, P Samson, L Ogata, H Azza, S Fourquet, P Gorvel, JP Heinzen, RA Raoult, D AF Renesto, Patricia Samson, Laurent Ogata, Hiroyuki Azza, Said Fourquet, Patrick Gorvel, Jean-Pierre Heinzen, Robert A. Raoult, Didier TI Identification of two putative rickettsial adhesins by proteomic analysis SO RESEARCH IN MICROBIOLOGY LA English DT Article DE rickettsiae; adhesin; rOmpB ID OUTER-MEMBRANE PROTEIN; MOUNTAIN-SPOTTED-FEVER; MULTIPLE SEQUENCE ALIGNMENTS; GREEN FLUORESCENT PROTEIN; MONOCLONAL-ANTIBODIES; BACTERIAL ADHERENCE; MASS-SPECTROMETRY; GENOME SEQUENCE; GUINEA-PIGS; HOST-CELLS AB The rickettsial membrane proteins that promote their uptake by eukaryotic host cells are unknown. To identify rickettsial ligand(s) that bind host cell surface proteins, biotinylated epithelial cells were used to probe a nitrocellulose membrane containing rickettsial extracts separated by SDS-PAGE. This overlay assay revealed that two close rickettsial ligands of approximately 32-30 kDa were recognized by host cells. Both proteins were identified using high resolution 2D-PAGE coupled with mass spectrometry analysis. One protein was identified as the C-terminal extremity of rOmpB called the beta-peptide. The second interacting protein was identified as a protein of unknown function encoded by RC 1281 and RP828 in Rickettsia conorii and in Rickettsia prowazekii, respectively, that shares strong similarities with other bacterial adhesins. Both proteins are highly conserved within the Rickettsia genus and might play a critical role in their pathogenicity. These data may have important implications for the development of future vaccines against rickettsial infections. (c) 2006 Elsevier SAS. All rights reserved. C1 Fac Med Marseille, IFR48, UMR 6020, CNRS,Unite Rickettsies, F-13385 Marseille, France. IBSM, CNRS, UPR 2589, Informat Genom & Struct, F-13288 Marseille, France. CIMI, F-13288 Marseille, France. NIAID, Lab Intracellular Parasites, NIH, Hamilton, MO USA. RP Renesto, P (reprint author), Fac Med Marseille, IFR48, UMR 6020, CNRS,Unite Rickettsies, 27 Blvd Jean Moulin, F-13385 Marseille, France. EM patricia.renesto@medecine.univ-mrs.fr RI Renesto, patricia/M-6105-2014; OI Gorvel, Jean-Pierre/0000-0002-2829-9804 NR 51 TC 42 Z9 49 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0923-2508 EI 1769-7123 J9 RES MICROBIOL JI Res. Microbiol. PD SEP PY 2006 VL 157 IS 7 BP 605 EP 612 DI 10.1016/j.resmic.2006.02.002 PG 8 WC Microbiology SC Microbiology GA 084WH UT WOS:000240564600001 PM 16574381 ER PT J AU Cusick, M Charles, MK Agron, E Sangiovanni, JP Ferris, FL Charles, S AF Cusick, Michael Charles, Marci K. Agron, Elvira Sangiovanni, John Paul Ferris, Frederick L., III Charles, Steve TI Anatomical and visual results of vitreoretinal surgery for stage 5 retinopathy of prematurity SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE retinopathy of prematurity; total retinal detachment; vitreoretinal surgery ID OPEN-SKY VITRECTOMY; RETROLENTAL FIBROPLASIA; CLOSED VITRECTOMY; V RETINOPATHY; FOLLOW-UP; VISION; ACUITY; CRYOTHERAPY; TRIAL; EYES AB Purpose: To provide a historical perspective on outcomes of surgery for infants with stage 5 retinopathy of prematurity (ROP) as perforned by a single surgeon over a 24-year period. Design: Retrospective observational cohort study. Methods: Setting: Clinical practice of the Charles Retina Institute. Patients: The 601 infants with stage 5 ROP in at least one eye who were referred for surgery between 1977 and 2001. Charts were reviewed for demographic data and postoperative anatomical and visual acuity outcomes in eyes that underwent surgery. Main Outcome Measures: The postoperative anatomical status of the retina and visual function were assessed after surgery. Anatomical outcome was categorized as success (macula attached), partial success (macula detached), failure (total retinal detachment), or lost eye (opaque cornea, secluded pupil, or phthisis). Visual function was classified as>20/ 200, 20/200 - 5/200, hand movement, light perception, or no light perception. Multivariable logistic regression was used to explore relationships between outcomes and baseline characteristics. Results: Only a minority of eyes had prior cryotherapy (15%) or laser photocoagulation (7%) therapy. The mean follow-up was 44 months for the 956 eyes treated surgically. The 608 eyes with available follow-up data were classified as follows: 28% success, 5% partial success, 55% failure, and 11 % lost eye. Visual function of light perception or better was achieved in 74% of the 183 eyes with data on visual acuity. Controlling for other baseline factors, early postpartum age at the time of surgery was a statistically significant predictor of failure/lost eye (OR = 2.08, 95% CI 1.09-3.97) and no light perception (OR = 5.13, 95% CI 1.45-18.14). Surgery for stage 5 ROP on the fellow eye was also a predictor of failure/lost eye (OR = 2.38, 95% CI 1.39-4.08). Conclusions: Surgery resulted in anatomical success for approximately one third of infant eyes with stage 5 ROP, and only a minority of eyes (8 of 183) achieved visual acuity better than 5/200. However, some initially successfully attached retinas redetached. Although this study is limited by follow-up and may represent a group of patients with a more vascularly active disease state due to the low proportion of patients with prior peripheral ablation, this cohort of infants provides results against which future interventions may be compared. C1 NEI, Div Epidemiol & Clin Res, NIH, CRC, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Univ Tennessee, Dept Ophthalmol, Memphis, TN USA. RP Cusick, M (reprint author), NEI, Div Epidemiol & Clin Res, NIH, CRC, Bldg 10,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM mxc@nei.nih.gov RI SanGiovanni, John Paul/A-7605-2008 NR 26 TC 18 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2006 VL 26 IS 7 BP 729 EP 735 DI 10.1097/01.iae.0000244268.21514.f7 PG 7 WC Ophthalmology SC Ophthalmology GA 180TQ UT WOS:000247389300003 PM 16963843 ER PT J AU Prenner, JL Capone, A Ciaccia, S Takada, Y Sieving, PA Trese, MT AF Prenner, Jonathan L. Capone, Antonio, Jr. Ciaccia, Stefano Takada, Yuichiro Sieving, Paul A. Trese, Michael T. TI Congenital x-linked retinoschisis classification system SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT Conference of the Pediatric-Retinal-Study-Group CY JAN 27-30, 2005 CL Hawks Cay, FL SP Pediat Retinal Study Grp ID JUVENILE RETINOSCHISIS; CELLS AB Purpose: To establish a classification system for congenital X-linked retinoschisis (CXLRS) using clinical examination and optical coherence tomography (OCT). Methods: Thirty-eight eyes of 19 patients who carried a clinical diagnosis of CXLRS were examined with OCT and clinical examination. Eyes were classified into one of four types based on a combination of clinical examination and OCT. Results: All patients had bilateral OCT scanning performed at an average age of 8.64 years (range 2.24-17.4 years). Review of OCT scans revealed that 37 of 38 eyes had foveal schisis (97%) while 31 of 38 (82%) eyes had macular schisis deeper than the nerve fiber layer in areas of ophthalmoscopically normal macular retina. The authors termed this flat schisis phenomenon lamellar schisis. Thirty of 38 (79%) had peripheral bullous schisis cavities present. Conclusions: OCT examinations of patients with CXLRS reveal lamellar schisis in areas of ophthalmoscopically normal macular retina in 82% of eyes with the clinical diagnosis of CXLRS. Using both clinical examination and OCT, the authors were able to identify foveal, lamellar, and peripheral schisis, lamellar schisis only identifiable by OCT. These findings allow the authors to propose a classification system. The authors hope this classification system will allow a better understanding of the natural history of CXLRS disease and allow testing of therapeutic options. C1 William Beaumont Hosp, Royal Oak, MI 48072 USA. NEI, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD 20892 USA. RP Prenner, JL (reprint author), 632 Wm Beaumont Med Bldg,3535 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM mgjt46@aol.com NR 9 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD SEP PY 2006 VL 26 IS 7 SU S BP S61 EP S64 DI 10.1097/01.iae.0000244290.09499.c1 PG 4 WC Ophthalmology SC Ophthalmology GA 176LK UT WOS:000247086400014 PM 16946682 ER PT J AU Ryu, OH Atkinson, JC Hoehn, GT Illei, GG Hart, TC AF Ryu, O. H. Atkinson, J. C. Hoehn, G. T. Illei, G. G. Hart, T. C. TI Identification of parotid salivary biomarkers in Sjogren's syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis SO RHEUMATOLOGY LA English DT Article DE Sjogren's syndrome; saliva; proteomics; 2D-DIGE; SELDI-TOF-MS ID PROTEOMIC PATTERNS; PANCREATIC-CANCER; GLAND BIOPSIES; PROTEINS; BETA-2-MICROGLOBULIN; LACTOFERRIN; DIAGNOSIS; DISEASE; EXPRESSION; MORTALITY AB Objectives. To identify the most significant salivary biomarkers in Sjogren's syndrome (SS) using proteomic methods. Methods. Parotid saliva from 20 non-SS subjects and 41 primary SS patients was analysed. Protein expression profiles for each sample were generated by surface-enhanced laser desorption/ionization time-of-flight-mass spectrometry (SELDI-TOF-MS). Mean peak intensities of SS patients and non-SS subjects were compared by univariate analyses. Samples pooled by diagnosis (SS and non-SS) and labelled with different Cy dyes were compared by two-dimensional difference gel electrophoresis (2D-DIGE). Two protein levels that were most significantly different by SELDI-TOF-MS and 2D-DIGE were validated by enzyme-linked immunosorbent assay in individual samples. Results. SELDI-TOF-MS of 10-200 kDa peaks revealed eight peaks with > 2-fold changes in the SS group that differed from non-SS at P < 0.005. Peaks of 11.8, 12.0, 14.3, 80.6 and 83.7 kDa were increased, while 17.3, 25.4, and 35.4 kDa peaks were decreased in SS samples. 2D-DIGE identified significant increases of beta-2-microglobulin, lactoferrin, immunoglobulin (Ig) kappa light chain, polymeric Ig receptor, lysozyme C and cystatin C in all stages of SS. Two presumed proline-rich proteins, amylase and carbonic anhydrase VI, were reduced in the patient group. Three of these ten biomarkers have not been associated previously with SS. Conclusions. The salivary proteomic profile of SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with non-SS. Future studies will test the ability of these biomarker levels, alone and in combination, to diagnose the salivary component of SS. C1 NIDCR, Human Craniofacial Genet Sect, NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIDCR, Clin Res Core, NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIDCR, Sjogrens Syndrome Clin, NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Hart, TC (reprint author), 10 Ctr Dr,Bldg 10,Room 5-2351, Bethesda, MD 20892 USA. EM thart@mail.nih.gov FU Intramural NIH HHS NR 50 TC 114 Z9 120 U1 4 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD SEP PY 2006 VL 45 IS 9 BP 1077 EP 1086 DI 10.1093/rheumatology/kei212 PG 10 WC Rheumatology SC Rheumatology GA 090BU UT WOS:000240926400005 PM 16522680 ER PT J AU Aletaha, D Machold, KP Nell, VPK Smolen, JS AF Aletaha, D. Machold, K. P. Nell, V. P. K. Smolen, J. S. TI The perception of rheumatoid arthritis core set measures by rheumatologists. Results of a survey SO RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; disease activity measures; clinical perception ID ERYTHROCYTE SEDIMENTATION-RATE; ACUTE-PHASE REACTANTS; C-REACTIVE PROTEIN; DISEASE-ACTIVITY; CLINICAL-TRIALS; RADIOLOGIC DAMAGE; ACTIVITY SCORE; CRITERIA; PROGRESSION; VALIDATION AB Objective. To investigate the perception of values of individual core set measures by rheumatologists, and how it differs across measures and across physicians. Methods. We designed a survey in which 44 international expert rheumatologists explicitly marked positions on the scales of seven core-set measures that in their opinion corresponded to cut-points between remission, low, moderate and high disease activity. The measures comprised swollen and tender joint counts (SJC, TJC), CRP, ESR, patient and evaluator global assessments of activity (PGA, EGA), and the Health Assessment Questionnaire Disability Index (HAQ). Results. The interpretation of measures across physicians was most consistent for ESR and PGA, while for CRP and joint counts there was most variation. Joint counts and CRP implied active disease at lower relative values (using normalized scales) than did PGA, EGA or ESR (P < 0.01 for most comparisons; Bonferroni-adjusted Wilcoxon signed rank test), and most physicians tended to tolerate higher numbers of tender joints than swollen joints to de. ne similar levels of disease activity. Given these cut-points, more RA patients in a typical cross-sectional cohort would be regarded as being in remission according to joint counts (SJC, 35%; TJC, 55%) than to global scores (PGA, 18%; EGA, 9%), and fewer patients would be regarded as being in remission by physician-derived or laboratory measures than by patient-derived ones. Conclusion. These data give insights into the integrative process of activity evaluation and will be informative for future survey designs, studies using physician opinion as the gold standard for criterion validity of disease activity, and allow 'activity mapping' of values on different scales based on expert opinion. C1 Med Univ Vienna, Dept Rheumatol, A-1090 Vienna, Austria. Lainz Hosp, Dept Med 2, A-1130 Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Aletaha, D (reprint author), Med Univ Vienna, Dept Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM daniel.aletaha@meduniwien.ac.at NR 29 TC 30 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD SEP PY 2006 VL 45 IS 9 BP 1133 EP 1139 DI 10.1093/rheumatology/kel074 PG 7 WC Rheumatology SC Rheumatology GA 090BU UT WOS:000240926400016 PM 16522674 ER PT J AU Mattai, AA Tossell, J Greenstein, DK Addington, A Clasen, LS Gornick, MC Seal, J Inoff-Germain, G Gochman, PA Lenane, M Rapoport, JL Gogtay, N AF Mattai, Anand A. Tossell, Julia Greenstein, Deanna K. Addington, Anjene Clasen, Liv S. Gornick, Michele C. Seal, Jeffrey Inoff-Germain, Gale Gochman, Peter A. Lenane, Marge Rapoport, Judith L. Gogtay, Nitin TI Sleep disturbances in childhood-onset schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE childhood-onset schizophrenia; sleep; disturbance ID AFFECTIVE-DISORDERS; K-SADS; CHILDREN; POLYMORPHISMS; METAANALYSIS; RELIABILITY; SCHEDULE; BEHAVIOR; QUALITY; G72/G30 AB Sleep disturbances in psychiatric disease have long been reported. However, research on sleep disturbances in child and adolescent psychiatric disorders is limited. We examined the relationship of sleep disturbance to clinical severity and co-morbid diagnoses (e.g. anxiety), for a population with childhood-onset schizophrenia (COS). Sixty-one COS patients underwent a medication-free inpatient observation period as part of an NIMH study of COS. Sleep quantity during the last 5-7 days of a patient's medication-firee period was measured using safety records and daily nursing notes. Subjects were divided into two groups: "good sleepers" (> 6 h) and "poor sleepers" (< 6 h) based on the average of total hours slept per night. Comparisons between groups were made with respect to clinical ratings at both admission and during washout period, co-morbid diagnosis of generalized anxiety disorder (GAD) and a susceptibility gene (G72) for COS. The median average sleep score for the entire group was 6.1 (S.D.= 2.01) h. The good and poor sleep groups differed significantly in terms of severity of positive symptoms (SAPS) and negative symptoms at admission (SANS) both on admission and during the medication-free period. There was no significant relationship between G72 genotypes and a past and/or present diagnosis of GAD. COS patients suffer from significant sleep disturbances and the sleep disturbance is highly related to the symptom severity. As there are numerous health implications of poor sleep, clinicians should have a low threshold for treating sleep disturbances in this population. (c) 2006 Elsevier B.V. All rights reserved. C1 NIMH, Child Psychiat Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, IRP, NIH, 10 Ctr Dr,Bldg 10,Room 3N-202, Bethesda, MD 20892 USA. EM gogtayn@intra.nimh.nih.gov RI Gogtay, Nitin/A-3035-2008 NR 38 TC 9 Z9 10 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2006 VL 86 IS 1-3 BP 123 EP 129 DI 10.1016/j.schres.2006.04.020 PG 7 WC Psychiatry SC Psychiatry GA 130BV UT WOS:000243775100015 PM 16730952 ER PT J AU Kozikowski, AP Roth, B Tropsha, A AF Kozikowski, Alan P. Roth, Bryan Tropsha, Alexander TI Why academic drug discovery makes sense SO SCIENCE LA English DT Letter C1 Univ Illinois, Drug Discovery Program, Chicago, IL 60612 USA. Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Case Western Reserve Univ, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Oncol, Cleveland, OH 44106 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Kozikowski, AP (reprint author), Univ Illinois, Drug Discovery Program, 833 S Wood St, Chicago, IL 60612 USA. EM kozikowa@uic.edu; bryan.roth@case.edu; alex_tropsha@unc.edu RI Tropsha, Alexander/G-6245-2014 NR 4 TC 19 Z9 19 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD SEP 1 PY 2006 VL 313 IS 5791 BP 1235 EP 1236 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 081JI UT WOS:000240313500014 PM 16946051 ER PT J AU Vodovotz, Y Chow, CC Bartels, J Lagoa, C Prince, JM Levy, RM Kumar, R Day, J Rubin, J Constantine, G Illiar, TR Fink, MP Clermont, G AF Vodovotz, Yoram Chow, Carson C. Bartels, John Lagoa, Claudio Prince, Jose M. Levy, Ryan M. Kumar, Rukmini Day, Judy Rubin, Jonathan Constantine, Greg Illiar, Timothy R. Fink, Mitchell P. Clermont, Gilles TI In silico models of acute inflammation in animals SO SHOCK LA English DT Review DE sepsis; trauma; mathematical model; inflammation; mouse; rat ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE PRODUCTION; TRANSFORMING GROWTH FACTOR-BETA-1; ESCHERICHIA-COLI ENDOTOXEMIA; HEMORRHAGIC-SHOCK; RESPONSE SYNDROME; BACTERIAL TRANSLOCATION; SYSTEMIC INFLAMMATION; CLINICAL-TRIALS; TRAUMA PATIENTS AB Trauma and hemorrhagic shock elicit an acute inflammatory response, predisposing patients to sepsis, organ dysfunction, and death. Few approved therapies exist for these acute inflammatory states, mainly due to the complex interplay of interacting inflammatory and physiological elements working at multiple levels. Various animal models have been used to simulate these phenomena, but these models often do not replicate the clinical setting of multiple overlapping insults. Mathematical modeling of complex systems is an approach for understanding the interplay among biological interactions. We constructed a mathematical model using ordinary differential equations that encompass the dynamics of cells and cytokines of the acute inflammatory response, as well as global tissue dysfunction. The model was calibrated in C57BI/6 mice subjected to (1) various doses of lipopolysaccharide (LPS) alone, (2) surgical trauma, and (3) surgery + hemorrhagic shock. We tested the model's predictive ability in scenarios on which it had not been trained, namely, (1) surgery +/- hemorrhagic shock + LPS given at times after the beginning of surgical instrumentation, and (2) surgery + hemorrhagic shock + bilateral femoral fracture. Software was created that facilitated fitting of the mathematical model to experimental data, as well as for simulation of experiments with various inflammatory challenges and associated variations (gene knockouts, inhibition of specific cytokines, etc.). Using this software, the C57Bl/6-specific model was recalibrated for inflammatory analyte data in CD14(-/-) mice and was used to elucidate altered features of inflammation in these animals. In other experiments, rats were subjected to surgical trauma LPS or to bacterial infection via fibrin clots impregnated with various inocula of Escherichia coli. Mathematical modeling may provide insights into the complex dynamics of acute inflammation in a manner that can be tested in vivo using many fewer animals than has been possible previously. C1 Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Math, Pittsburgh, PA 15213 USA. NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. Immunetrics Inc, Pittsburgh, PA USA. Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. RP Vodovotz, Y (reprint author), Univ Pittsburgh, Dept Surg, W1542 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. EM vodovotzy@upmc.edu RI Chow, Carson/A-7970-2009 FU Intramural NIH HHS; NHLBI NIH HHS [R01-HL-76157-02, R01-HL-080926]; NIGMS NIH HHS [1201-GM-67240-04, P50-GM-53789-09, R01-GM-67240-02, P50-GM-53789-08] NR 100 TC 55 Z9 58 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD SEP PY 2006 VL 26 IS 3 BP 235 EP 244 DI 10.1097/01.shk.0000225413.13866.fo PG 10 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 076HO UT WOS:000239947800003 PM 16912648 ER PT J AU Robertson, SJ Hasenkrug, KJ AF Robertson, Shelly J. Hasenkrug, Kim J. TI The role of virus-induced regulatory T cells in immunopathology SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; MIXED CRYOGLOBULINEMIA VASCULITIS; TRANSCRIPTION FACTOR FOXP3; IN-VITRO PROLIFERATION; AFRICAN-GREEN MONKEYS; HIV-INFECTED PATIENTS; DENDRITIC CELLS; TGF-BETA; IMMUNE ACTIVATION AB In recent years, regulatory T cells have received increased attention for their role in immune responses to microbial infections. The list of microbial pathogens associated with regulatory T cell responses is growing rapidly and includes bacteria, viruses, parasites, and fungi. As the biology of regulatory T cells is revealed, we are discovering that their induction during infection is a normal aspect of immunity, necessary to limit collateral damage from inflammatory responses and aggressive immunological effectors. Thus, these cells play a critical role in maintaining the delicate balance between preventing immunopathology and allowing the immune response to clear infections. While generally successful, there are notable exceptions where regulatory T cell-mediated suppression appears to be responsible for allowing certain viruses to establish and maintain a persistent state. In this review, we will discuss our current understanding of what virus-induced regulatory T cells are, how they are induced, and what mechanisms they use to suppress immunity. The complex role of Tregs in regulating immunity to viral infections, and the consequences their activity has on disease is illustrated by a review of specific viral infections including hepatitis C virus and human immunodeficiency virus. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Hasenkrug, KJ (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM KHasenkrug@nih.gov NR 148 TC 38 Z9 40 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD SEP PY 2006 VL 28 IS 1 BP 51 EP 62 DI 10.1007/s00281-006-0019-2 PG 12 WC Immunology; Pathology SC Immunology; Pathology GA 076KT UT WOS:000239957400007 PM 16841143 ER PT J AU Hall, PE Lathia, JD Miller, NGA Caldwell, MA Ffrench-Constant, C AF Hall, Peter E. Lathia, Justin D. Miller, Nigel G. A. Caldwell, Maeve A. Ffrench-Constant, Charles TI Integrins are markers of human neural stem cells SO STEM CELLS LA English DT Article DE fluorescence-activated cell sorting; neurosphere; prominin; laminin; extracellular matrix ID HEPATIC PROGENITOR CELLS; CENTRAL-NERVOUS-SYSTEM; SURFACE-MARKERS; PRECURSOR CELLS; LONG-TERM; MOUSE; EXPRESSION; PROTEIN; BETA-1-INTEGRINS; IDENTIFICATION AB The identification of markers for the isolation of human neural stem cells (hNSCs) is essential for studies of their biology and therapeutic applications. This study investigated expression of the integrin receptor family by hNSCs as potential markers. Selection of alpha 6(hi) beta 1(hi) cells by fluorescence-activated cell sorting led to an enrichment of human neural precursors, as shown by both neurosphere forming assays and increased expression of prominin-1, sox2, sox3, nestin, bmi1 and musashi1 in the beta 1(hi) population. Cells expressing high levels of beta 1(hi) integrin also expressed prominin-1 (CD133), a marker previously used to isolate hNSCs, and selection using integrin beta 1(hi) cells or prominin-1(hi) cells was found to be equally effective at enriching for hNSCs from neurospheres. Therefore, integrin subunits alpha 6 and beta 1 are highly expressed by human neural precursors and represent convenient markers for their prospective isolation. C1 Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 1QP, England. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Ffrench-Constant, C (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM cfc@mole.bio.cam.ac.uk FU Multiple Sclerosis Society [598]; Wellcome Trust NR 43 TC 89 Z9 93 U1 0 U2 12 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 2006 VL 24 IS 9 BP 2078 EP 2084 DI 10.1634/stemcells.2005-0595 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085YG UT WOS:000240639700010 PM 16690778 ER PT J AU Wiese, C Rolletschek, A Kania, G Navarrete-Santos, A Anisimov, SV Steinfarz, B Tarasov, KV Brugh, SA Zahanich, I Ruschenschmidt, C Beck, H Blyszczuk, P Czyz, J Heubach, JF Ravens, U Horstmann, O St-Onge, L Braun, T Brustle, O Boheler, KR Wobus, AM AF Wiese, Cornelia Rolletschek, Alexandra Kania, Gabriela Navarrete-Santos, Anne Anisimov, Sergey V. Steinfarz, Barbara Tarasov, Kirill V. Brugh, Sheryl A. Zahanich, Ihor Rueschenschmidt, Christiane Beck, Heinz Blyszczuk, Przemyslaw Czyz, Jaroslaw Heubach, Juergen F. Ravens, Ursula Horstmann, Olaf St-Onge, Luc Braun, Thomas Bruestle, Oliver Boheler, Kenneth R. Wobus, Anna M. TI Signals from embryonic fibroblasts induce adult intestinal epithelial cells to form nestin-positive cells with proliferation and multilineage differentiation capacity in vitro SO STEM CELLS LA English DT Article DE intestinal epithelium; mouse; nestin; embryonic fibroblasts; in vitro differentiation; Wnt; bone morphogenetic protein ID INTERMEDIATE-FILAMENT PROTEIN; NEURONAL PRECURSOR CELLS; STEM-CELLS; PROGENITOR CELLS; SKELETAL-MUSCLE; BETA-CATENIN; DOPAMINERGIC-NEURONS; GROWTH-FACTOR; SELF-RENEWAL; BONE-MARROW AB The intestinal epithelium has one of the greatest regenerative capacities in the body; however, neither stem nor progenitor cells have been successfully cultivated from the intestine. In this study, we applied an "artificial niche" of mouse embryonic fibroblasts to derive multipotent cells from the intestinal epithelium. Cocultivation of adult mouse and human intestinal epithelium with fibroblast feeder cells led to the generation of a novel type of nestin-positive cells (intestinal epithelium-derived nestin-positive cells [INPs]). Transcriptome analyses demonstrated that mouse embryonic fibroblasts expressed relatively high levels of Wnt/bone morphogenetic protein (BMP) transcripts, and the formation of INP's was specifically associated with an increase in Left, Wnt4, Wnt5a, and Wnt/BMP-responsive factors, but a decrease of BMP4 transcript abundance. In vitro, INPs showed a high but finite proliferative capacity and readily differentiated into cells expressing neural, pancreatic, and hepatic transcripts and proteins; however, these derivatives did not show functional properties. In vivo, INPs failed to form chimeras following injection into mouse blastocysts but integrated into hippocampal brain slice cultures in situ. We conclude that the use of embryonic fibroblasts seems to reprogram adult intestinal epithelial cells by modulation of Wnt/BMP signaling to a cell type with a more primitive embryonic-like stage of development that has a high degree of flexibility and plasticity. C1 Inst Plant Genet & Crop Plant Res, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany. Univ Halle Wittenberg, Inst Anat & Cell Biol, Halle, Germany. NIA, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Univ Bonn, Inst Reconstruct Neurobiol, Life & Brain Ctr, D-5300 Bonn, Germany. Hertie Fdn, D-5300 Bonn, Germany. Dresden Univ Technol, Dept Pharmacol & Toxicol, D-8027 Dresden, Germany. Max Planck Inst Heart & Lung Res, Bad Nauheim, Germany. Univ Gottingen, Fac Med, Surg Univ Clin, D-3400 Gottingen, Germany. DeveloGen AG, Gottingen, Germany. Univ Bonn, Dept Epileptol, D-5300 Bonn, Germany. RP Wobus, AM (reprint author), Inst Plant Genet & Crop Plant Res, In Vitro Differentiat Grp, Corrensstr 3, D-06466 Gatersleben, Germany. EM wobusam@ipk-gatersleben.de RI Braun, Thomas/B-2310-2008; OI Braun, Thomas/0000-0002-6165-4804 FU Intramural NIH HHS NR 65 TC 16 Z9 17 U1 1 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 2006 VL 24 IS 9 BP 2085 EP 2097 DI 10.1634/stemcells.2006-0008 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085YG UT WOS:000240639700011 PM 16741226 ER PT J AU Mankani, MH Kuznetsov, SA Wolfe, RM Marshall, GW Robey, PG AF Mankani, Mahesh H. Kuznetsov, Sergei A. Wolfe, Raymond M. Marshall, Grayson W. Robey, Pamela Gehron TI In vivo bone formation by human bone marrow stromal cells: Reconstruction of the mouse calvarium and mandible SO STEM CELLS LA English DT Article DE bone marrow stromal cells; xenogeneic stem cell transplantation; osteoprogenitor; long-term survival; long-term engraftment; culture; cellular therapy ID MEDIATED GENE-THERAPY; STEM-CELLS; SKULL DEFECTS; AGE; CRANIOPLASTY; REPAIR; REGENERATION; FIBROBLASTS; CAPACITY; MICE AB Bone marrow stromal cells (BMSCs) contain a subset of multipotent cells with the potential to repair hard-tissue defects. Mouse BMSCs, combined with a collagen carrier, can close critical-sized homologous mouse calvarial defects, but this new bone has a poor union with the adjacent calvarium. When human BMSCs are transplanted for the purpose of engineering new bone, best results can be achieved if the cells are combined with hydroxyapatite/ tricalcium phosphate (HA/TCP) particles. Here, we demonstrate that transplantation of cultured human BMSCs in conjunction with HA/TCP particles can be used successfully to close mouse craniofacial bone defects and that removal of the periosteum from the calvarium significantly enhances union with the transplant. Transplants were followed for up to 96 weeks and were found to change in morphology but not bone content after 8 weeks; this constitutes the first description of human BMSCs placed long-term to heal bone defects. New bone formation continued to occur in the oldest transplants, confirmed by tetracycline labeling. Additionally, the elastic modulus of this engineered bone resembled that of the normal mouse calvarium, and our use of atomic force microscopy (AFM)-based nanoindentation offered us the first opportunity to compare these small transplants against equally minute mouse bones. Our results provide insights into the long-term behavior of newly engineered orthotopic bone from human cells and have powerful implications for therapeutic human BMSC transplantation. C1 Univ Calif San Francisco, Dept Surg, Div Plast Surg, San Francisco, CA 94143 USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Mankani, MH (reprint author), Univ Calif San Francisco, Dept Surg, Div Plast Surg, 1001 Potrero Ave,Box 0807, San Francisco, CA 94143 USA. EM mmankani@sfghsurg.ucsf.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 34 TC 87 Z9 93 U1 0 U2 15 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD SEP PY 2006 VL 24 IS 9 BP 2140 EP 2149 DI 10.1634/stemcells.2005-0567 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085YG UT WOS:000240639700016 PM 16763200 ER PT J AU Hachinski, V Iadecola, C Petersen, RC Breteler, MM Nyenhuis, DL Black, SE Powers, WJ DeCarli, C Merino, JG Kalaria, RN Vinters, HV Holtzman, DM Rosenberg, GA Dichgans, M Marler, JR Leblanc, GG AF Hachinski, Vladimir Iadecola, Costantino Petersen, Ron C. Breteler, Monique M. Nyenhuis, David L. Black, Sandra E. Powers, William J. DeCarli, Charles Merino, Jose G. Kalaria, Raj N. Vinters, Harry V. Holtzman, David M. Rosenberg, Gary A. Dichgans, Martin Marler, John R. Leblanc, Gabrielle G. TI National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards SO STROKE LA English DT Review DE Binswangers disease; CADASIL; syndrome; cerebral infarction; cerebrovascular disorders; dementia; genetics; ischemia; lacunar infarction; leukoaraiosis; neuropsychology; stroke; vascular dementia ID WHITE-MATTER CHANGES; BOSTON NAMING TEST; TRANSGENIC MOUSE MODEL; BRAIN-BARRIER FUNCTION; VERBAL-LEARNING TEST; SPONTANEOUSLY HYPERTENSIVE RATS; AUTOSOMAL-DOMINANT ARTERIOPATHY; AMYLOID-BETA DEPOSITS; SMALL-VESSEL DISEASE; MINI-MENTAL STATE AB Background and Purpose-One in 3 individuals will experience a stroke, dementia or both. Moreover, twice as many individuals will have cognitive impairment short of dementia as either stroke or dementia. The commonly used stroke scales do not measure cognition, while dementia criteria focus on the late stages of cognitive impairment, and are heavily biased toward the diagnosis of Alzheimer disease. No commonly agreed standards exist for identifying and describing individuals with cognitive impairment, particularly in the early stages, and especially with cognitive impairment related to vascular factors, or vascular cognitive impairment. Methods-The National Institute for Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network (CSN) convened researchers in clinical diagnosis, epidemiology, neuropsychology, brain imaging, neuropathology, experimental models, biomarkers, genetics, and clinical trials to recommend minimum, common, clinical and research standards for the description and study of vascular cognitive impairment. Results-The results of these discussions are reported herein. Conclusions-The development of common standards represents a first step in a process of use, validation and refinement. Using the same standards will help identify individuals in the early stages of cognitive impairment, will make studies comparable, and by integrating knowledge, will accelerate the pace of progress. C1 Natl Inst Neurol Disorders & Stroke, NIH, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. London Hlth Sci Ctr, London, ON, Canada. Weill Cornell Med Coll, Div Neurobiol, Dept Neurol & Neurosci, New York, NY USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Univ Illinois, Dept Neurol & Rehabil, Chicago, IL 60680 USA. Sunnybrook & Womens Coll, Div Neurol, Hlth Sci Ctr, Toronto, ON, Canada. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63130 USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. Natl Inst Neurol Disorders & Stroke, Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Newcastle Gen Hosp, Wolfson Ctr Neuropathol, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Calif Los Angeles, Dept Pathol & Lab Med, Sect Neuropathol, Los Angeles, CA 90024 USA. Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 USA. Univ Munich, Klinikum Grosshadern, Neurol Klin, D-8000 Munich, Germany. RP Leblanc, GG (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Sect Stroke Diagnost & Therapeut, 6001 Execut Blvd,Room 2136, Bethesda, MD 20892 USA. EM leblancg@ninds.nih.gov RI DeCarli, Charles/B-5541-2009; crona, malin/B-7085-2012; Breteler, Monique /J-5058-2014; OI Black, Sandra/0000-0001-7093-8289; Merino, Jose/0000-0002-6676-0008 FU Medical Research Council [G0500247] NR 178 TC 592 Z9 693 U1 11 U2 59 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2006 VL 37 IS 9 BP 2220 EP 2241 DI 10.1161/01.STR.0000237236.88823.47 PG 22 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 101CG UT WOS:000241715900021 PM 16917086 ER PT J AU Powell, CL Kosyk, O Ross, PK Schoonhoven, R Boysen, G Swenberg, JA Heinloth, AN Boorman, GA Cunningham, ML Paules, RS Rusyn, I AF Powell, Christine L. Kosyk, Oksana Ross, Pamela K. Schoonhoven, Robert Boysen, Gunnar Swenberg, James A. Heinloth, Alexandra N. Boorman, Gary A. Cunningham, Michael L. Paules, Richard S. Rusyn, Ivan TI Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profiles in rat liver SO TOXICOLOGICAL SCIENCES LA English DT Article DE toxicogenomics; acetaminophen; nitrotyrosine; 8-hydroxy-deoxyguanosine; oxidative stress; lipid peroxidation ID INDUCED HEPATOTOXICITY; LIPID-PEROXIDATION; NITRIC-OXIDE; IN-VIVO; PROTEIN ADDUCTS; MICE; INHIBITION; TOXICOLOGY; TOXICITY; RADICALS AB Toxicogenomics provides the ability to examine in greater detail the underlying molecular events that precede and accompany toxicity, thus allowing prediction of adverse events at much earlier times compared to classical toxicological end points. Acetaminophen (APAP) is a pharmaceutical that has similar metabolic and toxic responses in rodents and humans. Recent gene expression profiling studies with APAP found an oxidative stress signature at a subtoxic dose that we hypothesized can be phenotypically anchored to conventional biomarkers of oxidative stress. Liver tissue was obtained from experimental animals used to generate microarray data, where male rats were given APAP at subtoxic (150 mg/kg) or overtly toxic (1500 and 2000 mg/kg) doses and sacrificed at 6, 24, or 48 h. Oxidative stress in liver was evaluated by a diverse panel of markers that included assessing expression of base excision repair (BER) genes, quantifying oxidative lesions in genomic DNA, and evaluating protein and lipid oxidation. A subtoxic dose of APAP produced significant accumulation of nitrotyrosine protein adducts. Both subtoxic and toxic doses caused a significant increase in 8-hydroxy-deoxyguanosine (8-OH-dG) as well as a significant decrease in glutathione (GSH) content. Only toxic doses of APAP significantly induced expression levels of BER genes. None of the doses examined resulted in a significant increase in the number of abasic sites or in the amount of lipid peroxidation. The accumulation of nitrotyrosine and 8-OH-dG adducts along with reduced GSH content in the liver phenotypically anchors the oxidative stress gene expression signature observed with a subtoxic dose of APAP, lending support to the validity of gene expression studies as a sensitive and biologically meaningful end point in toxicology. C1 Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, CB 7431, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU Intramural NIH HHS; NIEHS NIH HHS [U19 ES011391, K22 ES011660, K22-ES16660, P30 ES010126, P30-ES10126, P42 ES005948, P42-ES05948, R42 ES011746, R42-ES11746, T32 ES007126, T32-ES07126, U19-ES11391] NR 38 TC 56 Z9 60 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2006 VL 93 IS 1 BP 213 EP 222 DI 10.1093/toxsci/kfl030 PG 10 WC Toxicology SC Toxicology GA 074VI UT WOS:000239839500024 PM 16751229 ER PT J AU Barr, VA Balagopalan, L Barda-Saad, M Polishchuk, R Boukari, H Bunnell, SC Bernot, KM Toda, Y Nossal, R Samelson, LE AF Barr, Valarie A. Balagopalan, Lakshmi Barda-Saad, Mira Polishchuk, Roman Boukari, Hacene Bunnell, Stephen C. Bernot, Kelsie M. Toda, Yoko Nossal, Ralph Samelson, Lawrence E. TI T-cell antigen receptor-induced signaling complexes: Internalization via a cholesterol-dependent endocytic pathway SO TRAFFIC LA English DT Article DE adapter proteins; confocal microscopy; endocytosis; lipid rafts; signaling complexes; T-cell activation; ubiquitin ID CLATHRIN-INDEPENDENT ENDOCYTOSIS; GPI-ANCHORED PROTEINS; ADAPTER PROTEIN; MEMBRANE-PROTEIN; TYROSINE PHOSPHORYLATION; LYMPHOCYTE-ACTIVATION; NEGATIVE REGULATION; ACTIN CYTOSKELETON; PLASMA-MEMBRANE; LAT AB T-cell antigen receptor engagement causes the rapid assembly of signaling complexes. The adapter protein SLP-76, detected as SLP-yellow fluorescent protein, initially clustered with the TCR and other proteins, then translocated medially on microtubules. As shown by total internal reflection fluorescence microscopy and the inhibition of SLP-76 movement at 16 degrees C, this movement required endocytosis. Immunoelectron microscopy showed SLP-76 staining of smooth pits and tubules. Cholesterol depletion decreased the movement of SLP-76 clusters, as did coexpression of the ubiquitin-interacting motif domain from eps15. These data are consistent with the internalization of SLP-76 via a lipid raft-dependent pathway that requires interaction of the endocytic machinery with ubiquitinylated proteins. The endocytosed SLP-76 clusters contained phosphorylated SLP-76 and phosphorylated LAT. The raft-associated, transmembrane protein LAT likely targets SLP-76 to endocytic vesicles. The endocytosis of active SLP-76 and LAT complexes suggests a possible mechanism for downregulation of signaling complexes induced by TCR activation. C1 NCI, Cellular & Mol Biol Lab, Dept Hlth & Human Serv, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, CH, Italy. NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Tufts Univ, Dept Pathol, Boston, MA 02111 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Dept Hlth & Human Serv, Ctr Canc Res,NIH, Bldg 37, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU Intramural NIH HHS NR 68 TC 49 Z9 50 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-9219 J9 TRAFFIC JI Traffic PD SEP PY 2006 VL 7 IS 9 BP 1143 EP 1162 DI 10.1111/j.1600-0854.2006.00464.x PG 20 WC Cell Biology SC Cell Biology GA 072TE UT WOS:000239695100003 PM 16919152 ER PT J AU Grais, RF Ferrari, MJ Dubray, C Bjornstad, ON Grenfell, BT Djibo, A Fermon, F Guerin, PJ AF Grais, R. F. Ferrari, M. J. Dubray, C. Bjornstad, O. N. Grenfell, B. T. Djibo, A. Fermon, F. Guerin, P. J. TI Estimating transmission intensity for a measles epidemic in Niamey, Niger: lessons for intervention SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE measles; vaccination; epidemic modelling; reproductive ratio; Niger ID IMMUNIZATION STRATEGIES; DEVELOPING-COUNTRIES; DYNAMICS; VACCINATION; PATTERNS; IMPACT; PERSISTENCE; EFFICACY; MODEL AB The objective of this study is to estimate the effective reproductive ratio for the 2003-2004 measles epidemic in Niamey, Niger. Using the results of a retrospective and prospective study of reported cases within Niamey during the 2003-2004 epidemic, we estimate the basic reproductive ratio, effective reproductive ratio (RE) and minimal vaccination coverage necessary to avert future epidemics using a recent method allowing for estimation based on the epidemic case series. We provide these estimates for geographic areas within Niamey, thereby identifying neighbourhoods at high risk. The estimated citywide RE was 2.8, considerably Lower than previous estimates, which may help explain the long duration of the epidemic. Transmission intensity varied during the course of the epidemic and within different neighbourhoods (RE range: 1.4-4.7). Our results indicate that vaccination coverage in currently susceptible children should be increased by at least 67% (vaccine efficacy 90%) to produce a citywide vaccine coverage of 90%. This research highlights the importance of local differences in vaccination coverage on the potential impact of epidemic control measures. The spatial-temporal spread of the epidemic from district to district in Niamey over 30 weeks suggests that targeted interventions within the city could have an impact. (C) 2005 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. C1 Epicentre, F-75011 Paris, France. Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Minist Hlth, Niamey, Niger. Med Sans Frontieres, F-75011 Paris, France. RP Grais, RF (reprint author), Epicentre, 8 Rue St Sabin, F-75011 Paris, France. EM rebecca.grais@epicentre.msf.org RI Bjornstad, Ottar/I-4518-2012; OI Guerin, Philippe/0000-0002-6008-2963 NR 22 TC 20 Z9 20 U1 1 U2 6 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON W1N 1EY, ENGLAND SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD SEP PY 2006 VL 100 IS 9 BP 867 EP 873 DI 10.1016/j.trstmh.2005.10.014 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 072BW UT WOS:000239648600012 PM 16540134 ER PT J AU Fadeyi, EA Muniz, M Klein, H Leitman, SF Stroncek, D Wayne, A AF Fadeyi, E. A. Muniz, M. Klein, H. Leitman, S. F. Stroncek, D. Wayne, A. TI Neutropenia and pulmonary dysfunction associated with neutrophil specific antibody (HNA-2a) as a sign of TRALI: Report of a clinical look-back investigation SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 NIH, Bethesda, MD 20892 USA. EM fadeyie@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 14A EP 14A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100041 ER PT J AU Bernardin, F Stramer, SL Rehermann, B Tobler, LH Busch, MP Delwart, EL AF Bernardin, F. Stramer, S. L. Rehermann, B. Tobler, L. H. Busch, M. P. Delwart, E. L. TI High levels of truncated HCV genomes in NAT-yield blood donors with sero-silent infections SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 Blood Syst Res Inst, San Francisco, CA USA. Amer Red Cross, Natl Testing & Reference Labs, Gaithersburg, MD USA. NIDDKD, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. EM MBusch@bloodsystems.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 16A EP 16A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100047 ER PT J AU Spencer, BR Custer, B Kakaiya, RM Hillyer, KL Wilkinson, SL Gottschall, JL Steele, WR AF Spencer, B. R. Custer, B. Kakaiya, R. M. Hillyer, K. L. Wilkinson, S. L. Gottschall, J. L. Steele, W. R. TI Low risk for malaria transmission from presenting blood donors excluded for travel to Mexico SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 Amer Red Cross, Dedham, MA USA. Blood Ctr Pacific, Blood Syst Res Inst, San Francisco, CA USA. Inst Transfus Med, LifeSource Blood Serv, Glenview, IL USA. Amer Red Cross, Atlanta, GA USA. Hoxworth Blood Ctr, Cincinnati, OH USA. Blood Ctr Wisconsin, Milwaukee, WI USA. Westat Corp, Rockville, MD USA. NHLBI, Reds Study Grp 2, Rockville, MD USA. EM spencerb@usa.redcross.org NR 0 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 27A EP 27A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100080 ER PT J AU Bolan, CD Yau, Y Carter, CS Rehak, N Gladden, D Klein, HG Read, EJ Leitman, SF AF Bolan, C. D. Yau, Y. Carter, C. S. Rehak, N. Gladden, D. Klein, H. G. Read, E. J. Leitman, S. F. TI Optimization of peripheral blood progenitor cell (PBPC) collection by large volume leukapheresis (LVL): A 10 year history of continuous quality improvement SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM cbolan@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 30A EP 30A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100087 ER PT J AU Muniz, M Fadeyi, EA Gladden, SD Malech, H Pavletic, S Cecco, S Rehak, N Leitman, SF Bolan, CD AF Muniz, M. Fadeyi, E. A. Gladden, S. D. Malech, H. Pavletic, S. Cecco, S. Rehak, N. Leitman, S. F. Bolan, C. D. TI Symptomatic hypercalcemia due to intravenous (IV) calcium (Ca) prophylaxis during peripheral blood progenitor cell (PBPC) collection in patients with renal dysfunction SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. NCI, NIH, Graft Versus Host & Autoimmun Unit, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. EM munizm@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 49A EP 49A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100146 ER PT J AU Bryant, BJ Conry-Cantilena, C Stroncek, DF Ahlgren, AD Gibble, JW Leitman, SF AF Bryant, B. J. Conry-Cantilena, C. Stroncek, D. F. Ahlgren, A. D. Gibble, J. W. Leitman, S. F. TI Pasteurella multocida bacteremia in asymptomatic plateletpheresis donors SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Reston Hosp, Reston, VA USA. Greater Chesapeake & Potomac Amer Red Cross, Blood Serv, Baltimore, MD USA. EM bryantb2@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 50A EP 50A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100149 ER PT J AU Tran, M Fan, Y Carter, C Chau, QV Read, EJ AF Tran, M. Fan, Y. Carter, C. Chau, Q. V. Read, E. J. TI Quality of stored PBSC declines more rapidly at room temperature than 4 degrees C SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 NIH, Bethesda, MD 20892 USA. EM tranmh@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 60A EP 60A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100180 ER PT J AU Golding, H Park, S Nemo, G Todd, DS Busch, MP Khurana, S AF Golding, H. Park, S. Nemo, G. Todd, D. S. Busch, M. P. Khurana, S. TI Evaluation of a new immunoassay for differential diagnosis of HIV infections in the face of vaccine-induced antibodies SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Blood Syst & Res Inst, San Francisco, CA USA. EM hana.golding@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 104A EP 104A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100321 ER PT J AU Halverson, GR Tossas, E Velliquette, RW Reid, ME Frame, TH Castilho, L Baleotti, W Lee, AH AF Halverson, G. R. Tossas, E. Velliquette, R. W. Reid, M. E. Frame, T. H. Castilho, L. Baleotti, W., Jr. Lee, A. H. TI Production and characterization of murine anti-s monoclonal antibodies SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 New York Blood Ctr, New York, NY 10021 USA. Immucor Gamma, Houston, TX USA. Univ Estadual Campinas, Hemoctr, Campinas, SP, Brazil. NIH, Bethesda, MD 20892 USA. EM ghalverson@nybloodcenter.org RI Baleotti, Wilson Jr/C-3558-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 131A EP 131A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100407 ER PT J AU Smith, JD Procter, JL Read, EJ AF Smith, J. D. Procter, J. L. Read, E. J. TI Minimizing the Chaos: Organizing before the cellular therapy product arrives SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 NIH, Bethesda, MD 20892 USA. EM jsmith@mai1.cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 190A EP 191A PG 2 WC Hematology SC Hematology GA 084SG UT WOS:000240554100595 ER PT J AU Schlumpf, KS Glynn, SA Schreiber, GB Wright, DJ Tu, Y Reds, F AF Schlumpf, K. S. Glynn, S. A. Schreiber, G. B. Wright, D. J. Tu, Y. Reds, F. TI Predictors of donor return SO TRANSFUSION LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-of-Blood-Banks (AABB 2006) CY OCT 21-24, 2006 CL Miami Beach, FL SP Amer Assoc Blood Banks C1 Westat Corp, Rockville, MD USA. NHLBI, Bethesda, MD 20892 USA. EM karenschlumpf@westat.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 SU S BP 206A EP 206A PG 1 WC Hematology SC Hematology GA 084SG UT WOS:000240554100645 ER PT J AU Kurlander, RJ Tawab, A Fan, Y Carter, CS Read, EJ AF Kurlander, Roger J. Tawab, Abdul Fan, Yong Carter, Charles S. Read, Elizabeth J. TI A functional comparison of mature human dendritic cells prepared in fluorinated ethylene-propylene bags or polystyrene flasks SO TRANSFUSION LA English DT Article ID CLINICAL-SCALE GENERATION; MESSENGER-RNA; T-CELLS; CANCER-IMMUNOTHERAPY; SIGNAL-TRANSDUCTION; BLOOD MONOCYTES; CLOSED-SYSTEM; IN-VITRO; KAPPA-B; ANTIGEN AB BACKGROUND: Fluorinated ethylene-propylene (FEP) bags have been used instead of polystyrene (PS) flasks for ex vivo clinical-scale production of human dendritic cells (DCs) to facilitate closed-system recovery of these highly adherent cells. To assess the impact of DC culture on this nonadherent surface, the function of DCs generated in FEP and PS was compared. STUDY DESIGN AND METHODS: Cell yield, phenotype, cytokine production, migration, and antigen-presenting activity were measured in DCs prepared from peripheral blood monocytes in FEP bags or PS flasks with medium supplemented with serum, interleukin (IL)-4, and granulocyte-macrophage-colony-stimulating factor for 5 days to induce DC differentiation and CD40L or poly(I:C) plus interferon-gamma to promote maturation. RESULTS: DCs cultured in FEP or PS had comparable cell yield, viability, and CD83 and CCR7 expression. DCs generated in FEP, however, produced significantly less IL-12 and IL-10 during maturation, and differences persisted on rechallenge after harvest. FEP-cultured DCs migrated spontaneously or in response to CCR7 ligand more actively than PS-cultured DCs, but this difference was not significant. Mature DCs prepared in FEP and PS were equipotent in stimulating peptide-specific CD8 T-cell expansion in vitro. CONCLUSOINS: FEP- and PS-cultured DCs are similar in phenotype and in some functional measures, but FEP markedly reduces DC production of IL-12 and IL-10. This phenomenon presumably reflects intracellular changes linked to the absence of a surface for firm cell adherence. Given the importance of these cytokines in the immune response, these changes could have a significant impact on DC function in vivo. C1 NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Kurlander, RJ (reprint author), NIH, Ctr Clin, Dept Lab Med, Bldg 10,Room 2C373,10 Ctr Dr, Bethesda, MD 20892 USA. EM rkurlander@nih.gov NR 44 TC 13 Z9 13 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 BP 1494 EP 1504 DI 10.1111/j.1537-2995.2006.00940.x PG 11 WC Hematology SC Hematology GA 079AD UT WOS:000240147000008 PM 16965575 ER PT J AU Renoud, KJ Barracchini, K Byrne, KM Adams, S Pickett, A Caruccio, L Stroncek, DF AF Renoud, Keli J. Barracchini, Kathleen Byrne, Karen M. Adams, Sharon Pickett, Angela Caruccio, Lorraine Stroncek, David F. TI KEL6 and KEL7 genotyping with sequence-specific primers SO TRANSFUSION LA English DT Article ID BLOOD-GROUP PROTEIN; MOLECULAR-BASIS; PHENOTYPE; CELL AB BACKGROUND: Although antibodies to Js(a) and Js(b) are clinically significant, reagent-quality anti-Js(a) and anti-Js(b) are not readily available. A sequence-specific primer-polymerase chain reaction (SSP-PCR) genotyping assay was tested that makes use of two single-nucleotide polymorphisms (SNPs) at positions 1910 and 2019 of KEL. These SNPs distinguish the gene encoding Js(a), KEL6; and Js(b), KEL7. STUDY DESIGN AND METHODS: Four primer sets that selectively amplified KEL6 and KEL7 from genomic DNA were developed. Two sets detected the SNP at bp 1910 and two sets detected the bp 2019 SNP. KEL6 and KEL7 genotyping and Js(a) and Js(b) phenotyping results were compared among 64 subjects. RESULTS: The SSP-PCRs were specific for KEL6 and KEL7 when testing DNA for three donors of known Js phenotype: Js(a+b-), Js(a-b+), and Js(a+b+). Genotyping results for the 1910 SNP were identical to the phenotyping results in all 64 subjects, but for the 2019 SNP, the genotyping and phenotyping results were identical for only 49 subjects. In 12 subjects with the Js(a-b+) phenotype, the 2019 SNP was heterozygous KEL6, KEL7; in 2 with Js(a-b+) and in 1 with Js(a+b+), the 2019 SNP was homozygous KEL6. CONCLUSION: KEL 2019-bp SNP does not always correlate with the Js phenotype owing to the presence of an atypical KEL gene with a KEL7 polymorphism at 1910 and a KEL6 polymorphism at 2019. The KEL polymorphism at 2019 is silent and this allele yields a Js(a-b+) phenotype. Only analysis of the 1910-bp SNP can be used to genotype KEL6 and KEL7. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711,10 Ctr Dr MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@dtm.cc.nih.gov NR 12 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2006 VL 46 IS 9 BP 1510 EP 1514 DI 10.1111/j.1537-2995.2006.00937.x PG 5 WC Hematology SC Hematology GA 079AD UT WOS:000240147000010 PM 16965577 ER PT J AU Kamhawi, S AF Kamhawi, Shaden TI Phlebotomine sand flies and Leishmania parasites: friends or foes? SO TRENDS IN PARASITOLOGY LA English DT Review ID VECTOR LUTZOMYIA-LONGIPALPIS; TARGETED GENE DELETION; MACROPHAGES IN-VITRO; MAJOR INFECTIONS; MOLECULAR CHARACTERIZATION; METACYCLIC PROMASTIGOTES; LIPOPHOSPHOGLYCAN LPG; VIANNIA BRAZILIENSIS; FLY INTERACTIONS; MESSENGER-RNAS AB Leishmania parasites need phlebotomine sand flies to complete their life cycle and to propagate. This review looks at Leishmania-sand fly interactions as the parasites develop from amastigotes to infectious metacyclics, highlighting recent findings concerning the evolutionary adaptations that ensure survival of the parasites. Such adaptations include secretion of phosphoglycans, which protect the parasite from digestive enzymes; production of chitinases that degrade the stomodeal valve of the sand fly; secretion of a neuropeptide that arrests midgut and hindgut peristalsis; and attaching to the midgut to avoid expulsion. C1 NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kamhawi, S (reprint author), NIAID, Intracellular Parasite Biol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM skamhawi@niaid.nih.gov NR 60 TC 131 Z9 136 U1 1 U2 27 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD SEP PY 2006 VL 22 IS 9 BP 439 EP 445 DI 10.1016/j.pt.2006.06.012 PG 7 WC Parasitology SC Parasitology GA 082GU UT WOS:000240375500008 PM 16843727 ER PT J AU Lee, W Deter, RL McNie, B Powell, M Balasubramaniam, M Goncalves, LF Espinoza, J Romero, R AF Lee, W. Deter, R. L. McNie, B. Powell, M. Balasubramaniam, M. Goncalves, L. F. Espinoza, J. Romero, R. TI Quantitative and morphological assessment of early gestational sacs using three-dimensional ultrasonography SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE first trimester; sac volume; three-dimensional ultrasonography; VOCAL ID 1ST TRIMESTER; ULTRASOUND VOLUMETRY; NORMAL PREGNANCIES; IMPLANTATION; GROWTH; REPRODUCIBILITY; BLASTOCYST; DEFECTS; EMBRYO; SONAR AB Objective Our main objective was to determine the value of three-dimensional ultrasonograpby (3DUS) and Virtual Organ Computer-aided AnaLysis (VOCAL (TM)) in the evaluation of gestational sac volume and morphology during early pregnancy. Methods Twenty-eight normal early pregnancies were scanned approximately every 2 weeks using transabdominal (TAS) and transvaginal (TVS) sonography. The VOCAL technique was used to create computerized surface models to classify gestational sac shapes as discoid or ellipsoid. Serial sac volume changes were analyzed using repeated measures ANOVA. Bland-Altman plots determined examiner bias and limits of agreement (LOA) for sac volume measurements. Gestational sac volumes were compared between the two-dimensional (2D) ellipsoid and VOCAL techniques. Differences between volume measurements were tested using the two-tailed paired t-test witb statistical significance at the P < 0.05 level. Results Each subject was examined at a mean SD menstrual age of 7.9 +/- 0.6 weeks (Scan 1), 9.9 +/- 0.6 weeks (Scan 2), and 11.9 +/- 0.6 weeks (Scan 3). Sac volumes significantly increased over time from 22 +/- 11 mL at Scan 1, to S7 +/- 21 mL at Scan 2 and 116 +/- 3SmL at Scan 3 (P < 0.001). Predominant sac shapes were classified as ellipsoid (76.2%) or discoid (23.8%). Additional descriptors included: concave (60.7%), irregular (53.6%), or smooth (7.1%), with 19% of the overall group having more than one additional shape attribute. Clinically acceptable volume measurement bias and agreement were found for the following comparisons: (1) TAS versus TVS; (2) interobserver volume measurements; and (3) intraobserver volume measurements. The VOCAL technique yielded slightly greater sac volumes (64 +/- 45.4 mL) when compared to the 2D ellipsoid model (48.6 +/- 36.8 mL) (28.9 +/- 24.3% (95% limit of agreement range, -18.7 to 76.5%), P < 0.001). Conclusions Reproducible sac volume measurements can be obtained using VOCAL with either TAS or TVS. Early gestational sacs variably appear as discoid or ellipsoid structures with a concave indentation from the placenta. Sac volumes can be underestimated if an ellipsoid shape is assumed. Morphological and quantitative analysis-of the gestational sac may provide baseline parameters for studying patients at risk for early pregnancy failure. Copyright (c) 2006 ISUOG. Published by John Wiley & Sons, Ltd. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. NICHD, DHHS, Perinatol Res Branch, NIH, Bethesda, MD USA. NICHD, DHHS, Perinatol Res Branch, NIH, Detroit, MI USA. Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. William Beaumont Hosp, Res Inst, Div Biostat, Royal Oak, MI USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu FU Intramural NIH HHS NR 33 TC 16 Z9 16 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD SEP PY 2006 VL 28 IS 3 BP 255 EP 260 DI 10.1002/uog.2840 PG 6 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 087QV UT WOS:000240758100005 PM 16937412 ER PT J AU Reeve, BB Potosky, AL Willis, GB AF Reeve, Bryce B. Potosky, Arnold L. Willis, Gordon B. TI Should function and bother be measured and reported separately for prostate cancer quality-of-life domains? SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; SEXUAL FUNCTION; MEN; OUTCOMES; THERAPY; RADIATION; CAPSURE; INDEX AB Objectives. To evaluate the psychometric properties of the three domains bowel, urinary, and sexual function as they were measured in the Prostate Cancer Outcomes Study and examine their use in different research and practice settings. Leading prostate cancer health-related quality-of-life questionnaires include questions that measure patients' bowel, urinary, and sexual function and their perceived annoyance (or bother) caused by limited functioning. The published results are mixed on reporting function and bother independently or together as a single domain. Methods. Statistical tools from classical measurement theory and factor analytic methods were used to evaluate the psychometric properties of the Prostate Cancer Outcomes Study disease-specific scales. The findings from studies of other prostate cancer outcomes scales and clinical input were included to formulate the conclusions. Results. Factor analysis results uncovered a multidimensional structure within two of the three domains. The urinary domain consisted of items measuring two factors: incontinence and urinary obstructive symptoms. Sexual dysfunction consisted of two dimensions: interest in sexual activity and erectile function. Conclusions. These empirical results suggest that bowel dysfunction and urinary incontinence can each be combined with measures of bother to produce overall measures of function; however, evidence was present for the need for separate measures of sexual function, sexual interest, and perceived bother with sexual function. For informing patient-doctor communications, function and bother on all three domains should be reported separately, because treatment decisions or symptom management may vary depending on a patient's perceived concern about their health-related quality-of-life. (c) 2006 Elsevier Inc. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Reeve, BB (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,MSC 7344,EPN Room 4005, Bethesda, MD 20892 USA. EM reeveb@mail.nih.gov NR 17 TC 14 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD SEP PY 2006 VL 68 IS 3 BP 599 EP 603 DI 10.1016/j.urology.2006.003.037 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 101EL UT WOS:000241721600033 PM 16979720 ER PT J AU Hoenerhoff, MJ Starost, MF Ward, JM AF Hoenerhoff, M. J. Starost, M. F. Ward, J. M. TI Eosinophilic crystalline pneumonia as a major cause of death in 129S4/SvJae mice SO VETERINARY PATHOLOGY LA English DT Article DE acidophilic macrophage pneumonia; crystalline pneumonitis; eosinophilic crystalline pneumonia; transgenic mice; Ym1 protein ID EXPRESSION; YM1; CHITINASE; IDENTIFICATION; INFLAMMATION; INFECTION; PATHOLOGY; PROTEIN; LECTIN; LUNGS AB Eosinophilic crystalline pneumonia is an idiopathic disease that occurs in many strains and stocks of mice, more commonly in strains on a C57BL/6 background. The disease occurs sporadically in most strains of mice and varies from mild and subclinical to severe and fulminating, sometimes resulting in respiratory distress and death. In this study, 94 aged male and female 129S4/SvJae mice were evaluated for eosinophilic crystalline pneumonia lesions. There was an 87% incidence, with females overrepresented. Histologically, there were multifocal to coalescing inflammatory infiltrates composed of numerous large eosinophilic macrophages and multinucleate cells admixed with eosinophils, neutrophils, lymphocytes, and plasma cells within alveolar and bronchiolar spaces, associated with refractile, brightly eosinophilic, angular crystals. Alveolar macrophages and multinucleate cells contained fine needlelike to rectangular intracytoplasmic crystalline material. Similar crystals were often free within alveoli and conducting airways, often associated with mucous metaplasia of bronchiolar epithelium. This disease may occur spontaneously or in concert with other pulmonary lesions, such as pulmonary adenomas, lymphoproliferative disease, allergic pulmonary disease, and parasitic or fungal infections. The characteristic crystals morphologically resemble Charcot-Leyden crystals, which represent eosinophil breakdown products in humans with eosinophil-related disease. However, crystals in eosinophilic crystalline pneumonia are composed predominantly of Ym1 protein, a chitinase-like protein associated with neutrophil granule products and secreted by activated macrophages. The function of Ym1 protein is not fully understood but is believed to be involved in host immune defense, eosinophil recruitment, and cell-cell and cell-matrix interactions consistent with tissue repair. The mechanism of induction of eosinophilic crystalline pneumonia with Ym1 crystal formation is unknown. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Off Res Serv, Div Vet Resources, Bethesda, MD USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Hoenerhoff, MJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, 41 Lib Dr,Bldg 41,Room C619, Bethesda, MD 20892 USA. EM hoenerhm@mail.nih.gov FU Intramural NIH HHS NR 19 TC 31 Z9 31 U1 0 U2 2 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD SEP PY 2006 VL 43 IS 5 BP 682 EP 688 DI 10.1354/vp.43-5-682 PG 7 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 086VU UT WOS:000240701900009 PM 16966445 ER PT J AU Robinson, HL Montefiori, DC Villinger, F Robinson, JE Sharma, S Wyatt, LS Earl, PL McClure, HM Moss, B Amara, RR AF Robinson, Harriet L. Montefiori, David C. Villinger, Francois Robinson, James E. Sharma, Sunita Wyatt, Linda S. Earl, Patricia L. McClure, Harold M. Moss, Bernard Amara, Rama Rao TI Studies on GM-CSF DNA as an adjuvant for neutralizing Ab elicited by a DNA/MVA immunodeficiency virus vaccine SO VIROLOGY LA English DT Article DE immunodeficiency virus vaccine; DNA/MVA vaccine; GM-CSF DNA adjuvant; neutralizing Ab; avidity of Ab; re-emergent virus protection ID COLONY-STIMULATING FACTOR; T-CELL RESPONSES; CXC CHEMOKINE RECEPTOR-5; RHESUS-MONKEYS; IN-VIVO; IMMUNE-RESPONSES; ANTIBODY-RESPONSES; DENDRITIC CELLS; ENVELOPE GLYCOPROTEIN; MUCOSAL CHALLENGE AB Here, we use a vaccine consisting of DNA priming followed by MVA boosting in rhesus macaques to investigate the ability of GM-CSF DNA to serve as an adjuvant for the elicitation of neutralizing Ab against an HIV-1 Env. The trial used Gag, Pol, and Env sequences from SHIV-89.6 in the immunogens and a neutralization escape variant of SHIV-89.6, SHIV-89.6P, for challenge. Co-delivery of GM-CSF and vaccine DNAs enhanced the temporal appearance of neutralizing Ab and broadened the specificity of the neutralizing activity to include SHIV-89.6P. Two long-term SHIV-89.6 infections elicited neutralizing activity for SHIV-89.6 but not SHIV-89.6P. Studies on the avidity of the anti-Env antisera revealed that the GM-CSF-adjuvanted vaccine had elicited higher avidity Ab than the non-adjuvanted vaccine or the infection. The GM-CSF-adjuvanted group showed a trend towards better control of the challenge infection and had better control of re-emergent virus (P < 0.01) than the nonadjuvanted group. (c) 2006 Elsevier Inc. All rights reserved. C1 Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Duke Univ, Ctr Med, Dept Surg, Durham, NC 27710 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Robinson, HL (reprint author), Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. EM hrobins@nny.emory.edu FU NCRR NIH HHS [P51 RR00165]; NIAID NIH HHS [AI 85343, AI46275, P01 AI43045, R01 AI046275, P01 AI043045]; NIDA NIH HHS [P30 DA12121] NR 57 TC 41 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2006 VL 352 IS 2 BP 285 EP 294 DI 10.1016/j.virol.2006.02.011 PG 10 WC Virology SC Virology GA 080CV UT WOS:000240225400003 PM 16740288 ER PT J AU Oh, SK Stegman, B Pendleton, CD Ota, MO Pan, CH Griffin, DE Burke, DS Berzofsky, JA AF Oh, SangKon Stegman, Brian Pendleton, C. David Ota, Martin O. Pan, Chien-Hsiung Griffin, Diane E. Burke, Donald S. Berzofsky, Jay A. TI Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus SO VIROLOGY LA English DT Article DE measles; vaccines; CDS; cytotoxic T lymphocytes; epitopes ID CYTOTOXIC T-LYMPHOCYTES; COMPLETE NUCLEOTIDE-SEQUENCE; CLASS-I; VACCINIA VIRUS; MATERNAL ANTIBODIES; ENCODING MEASLES; RHESUS MACAQUES; NATURAL MEASLES; CELL RESPONSES; HUMORAL-IMMUNE AB Natural infection and vaccination with a live-attenuated measles virus (NW) induce CD8(+) T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8(+) T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (119-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K(b) and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection. Published by Elsevier Inc. C1 Baylor Univ, Ctr Med, Baylor Inst Immunol Res, Dallas, TX 75204 USA. NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Oh, SK (reprint author), Baylor Univ, Ctr Med, Baylor Inst Immunol Res, 3434 Live Oak, Dallas, TX 75204 USA. EM sangkono@baylorhealth.edu; berzofsk@helix.nih.gov RI Pan, Chien-Hsiung/E-3857-2010; Pan, Chien-Hsiung/K-6922-2013; OI /0000-0002-5704-8094 FU Intramural NIH HHS NR 60 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2006 VL 352 IS 2 BP 390 EP 399 DI 10.1016/j.virol.2006.04.040 PG 10 WC Virology SC Virology GA 080CV UT WOS:000240225400013 PM 16781760 ER PT J AU Sanders, JM Lebetkin, EH Chen, LJ Burka, LT AF Sanders, J. M. Lebetkin, E. H. Chen, L. -J. Burka, L. T. TI Disposition of 2,2',4,4,5,5'-hexabromodiphenyl ether (BDE153) and its interaction with other polybrominated diphenyl ethers (PBDEs) in rodents SO XENOBIOTICA LA English DT Article DE polybrominated diphenyl ethers (PBDEs); metabolism and disposition; persistent organic pollutants ID BROMINATED FLAME RETARDANTS; EXPOSURE; RATS; MICE; ENVIRONMENT; METABOLISM; COMPONENTS; SINGLE; TREND AB The disposition of the C-14-labelled polybrominated diphenyl ether (PBDE) 2,2',4,4',5,5'-hexaBDE (BDE153) was investigated in rodents following single and multiple doses and in a mixture with radiolabelled 2,2,4,4-tetraBDE (BDE47) and 2,2',4,4',5-pentaBDE (BDE99). In single exposure studies there was little or no effect of dose on BDE153 disposition in male rats in the range 1-100 mu mol kg(-1). No major sex or species differences in the in vivo fate of BDE153 were detected. BDE153 was absorbed in rats or mice following gavage by approximately 70%; retained in tissues; and poorly metabolized and slowly excreted. Mixture studies indicated that, relative to each other, more BDE47 was distributed to adipose tissue, more BDE153 accumulated in the liver, and BDE99 was metabolized to the greatest extent. BDE153 was probably retained in the liver due to minimal metabolism and elimination after 'first-pass' distribution to the tissue following gavage. C1 NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Sanders, JM (reprint author), NIEHS, Lab Pharmacol & Chem, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM sander10@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 20 TC 24 Z9 24 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD SEP PY 2006 VL 36 IS 9 BP 824 EP 837 DI 10.1080/00498250600815906 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 093FT UT WOS:000241154200007 PM 16971346 ER PT J AU Kim, DJ Chung, JH Ryu, EK Rhim, JH Ryu, YS Park, SH Kim, KT Kang, HS Chung, HK Park, SC AF Kim, Dong-Jo Chung, Jun-Ho Ryu, Eun-Kyeong Rhim, Jung-Hyo Ryu, Yoon-Sic Park, So-Hyun Kim, Kyung Tae Kang, Heun-Soo Chung, Hong-Keun Park, Sang Chul TI Metabolic loading of guanosine induces chondrocyte apoptosis via the Fas pathway SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE apoptosis; chondrocytes; ossification; Fas; ligand; guanosine ID ADENOSINE-INDUCED APOPTOSIS; CELLS; CARTILAGE; CULTURE; LIGAND AB Although the apoptosis of chondrocytes plays an important role in endochondral ossification, its mechanism has not been elucidated. In this study, we show that guanosine induces chondrocyte apoptosis based on the results of acridine orange/ ethidium bromide staining, caspase-3 activation, and sub-G1 fraction analysis. The potent inhibitory effect of dipyridamole, a nucleoside transporter blocker, indicates that extracellular guanosine must enter the chondrocytes to induce apoptosis. We found that guanosine promotes Fas-Fas ligand interaction which, in turn, leads to chondrocyte apoptosis. These findings indicate a novel mechanism for endochondral ossification via metabolic regulation. C1 Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Metab Engn Lab Inc, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Xenotransplantat Res Ctr, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Aging & Apoptosis Res Ctr, Seoul 110799, South Korea. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Park, SC (reprint author), Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 110799, South Korea. EM scpark@snu.ac.kr NR 17 TC 0 Z9 2 U1 0 U2 0 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD AUG 31 PY 2006 VL 38 IS 4 BP 401 EP 407 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 082FQ UT WOS:000240372500008 PM 16953119 ER PT J AU Ballas, SK Barton, FB Waclawiw, MA Swerdlow, P Eckman, JR Pegelow, CH Koshy, M Barton, BA Bonds, DR AF Ballas, Samir K. Barton, Franca B. Waclawiw, Myron A. Swerdlow, Paul Eckman, James R. Pegelow, Charles H. Koshy, Mabel Barton, Bruce A. Bonds, Duane R. TI Hydroxyurea and sickle cell anemia: effect on quality of life SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MEDICAL OUTCOMES; RISK-FACTORS; DISEASE; PAIN; HEMOGLOBIN; GABAPENTIN; NEUROPATHY AB Background: The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell ( SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals. Methods: The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of llife (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit perceptible to the patients. HQOL was assessed with the Profile of Mood States, the Health Status Short Form 36 (SF-36), including 4-week pain recall, and the Ladder of Life, self-administered twice 2-weeks apart pre-treatment and every 6 months during the two-year, randomized, double-blind, treatment phase. The effects of factors including randomized treatment, age, gender, pre-treatment crises frequency, Hb-F level mean, daily pain from 4-week pre-treatment diaries, and 2-year Hb-F response level ( low or high) were investigated. Results: Over two years of treatment, the benefit of HU treatment on QOL, other than pain scales, was limited to those patients taking HU who maintained a high HbF response, compared to those with low HbF response or on placebo. These restricted benefits occurred in social function, pain recall and general health perception. Stratification according to average daily pain prior to treatment showed that responders to HU whose average daily pain score was 5 - 9 ( substantial pain) achieved significant reduction in the tension scale compared to the placebo group and to non-responders. HU had no apparent effect on other QOL measures. Conclusion: Treatment of SS with HU improves some aspects of QOL in adult patients who already suffer from moderate-to-severe SS. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Cardeza Fdn, Philadelphia, PA 19107 USA. Maryland Med Res Inst, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI USA. Emory Univ, Atlanta, GA 30322 USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Illinois Chicago Hosp, Chicago, IL USA. RP Ballas, SK (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Cardeza Fdn, Philadelphia, PA 19107 USA. EM samir.ballas@jefferson.edu; fbb8@georgetown.edu; mw4t@nih.gov; swerdlow@karmanos.org; james_eckman@emoryhealthcare.org; cpegelow@miami.edu; mabelkoshy@hotmail.com; bbarton@mmri.org; db56g@nih.gov OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [U01 HL 45696, N01HB67129, N01-HB-67129, U01 HL 45692] NR 26 TC 45 Z9 47 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD AUG 31 PY 2006 VL 4 AR 59 DI 10.1186/1477-7525-4-59 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 091NN UT WOS:000241035700001 PM 16942629 ER PT J AU Marques-Deak, A Cizza, G Eskandari, F Torvik, S Christie, IC Sternberg, EM Phillips, TM AF Marques-Deak, Andrea Cizza, Giovanni Eskandari, Farideh Torvik, Sara Christie, Israel C. Sternberg, Esther M. Phillips, Terry M. CA The P O W E R Study Group TI Measurement of cytokines in sweat patches and plasma in healthy women: Validation in a controlled study SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cytokines; chemokines; eccrine gland; recycling immunoaffinity chromatography ID RECYCLING IMMUNOAFFINITY CHROMATOGRAPHY; MAJOR DEPRESSIVE DISORDER; INFLAMMATORY MARKERS; TNF-ALPHA; ANTIINFLAMMATORY CYTOKINES; PROINFLAMMATORY CYTOKINES; CEREBROSPINAL-FLUID; LINEAR-REGRESSION; OLDER-ADULTS; SERUM-LEVELS AB Cytokines have been detected by ELISA in a variety of body fluids. Recycling immunoaffinity chromatography (RIC) coupled with laser-induced fluorescence detection is a highly sensitive and specific method, which allows simultaneous measurements of many analytes in small volumes of biological fluids. This method has been applied to plasma, cervical secretions and other body fluids, but has not previously been applied to sweat. The aim of this study was to validate the RIC methodology in sweat for measurements of IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, IL-8 and TGF-beta. Two sweat patches were applied for 24 h on the torso, and blood was collected atone time point during this period in nine healthy women. Cytokines were measured in paired samples of plasma and sweat. Cytokines were detected in sweat in similar concentrations to plasma. Linear regression analysis confirmed that sweat levels of these cytokines accounted fora large percentages of variance in plasma levels: IL-1 alpha (R-2 = 0.70, p = 0.005), IL-1 beta (R-2 = 0.79, p = 0.003), IL-6 (R-2 = 0.52, p = 0.03), TNF-alpha (R-2 = 0.95, p < 0.0001), IL-8 (R-2 = 0.81, p = 0.001) and TGF-beta (R-2 = 0.94, p = 0.0003). These findings indicate that cytokine levels measured in sweat are informative of circulating levels and that sweat patches combined with RIC represents a viable non-invasive method to measure cytokines in ambulatory settings over time. This method is unobtrusive and requires minimal active compliance on the part of the subjects being studied, without pain or stress. This approach can open a new generation of studies to address the effects of environmental factors on immune responses in a wide range of different settings. Published by Elsevier B.V. C1 NIMH, Sect Neuroendocrine Immunol, NIH, Rockville, MD 20852 USA. NIMH, Behav Integrat Neural Immune Program, NIH, Rockville, MD 20852 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NIH, Ultramicro Analyt Immunochem Resource, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol, NIH, 5625 Fishers Lane,MSC-9401, Rockville, MD 20852 USA. EM sternbee@mail.nih.gov FU Intramural NIH HHS NR 58 TC 23 Z9 23 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 31 PY 2006 VL 315 IS 1-2 BP 99 EP 109 DI 10.1016/j.jim.2006.07.011 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 095ER UT WOS:000241291500012 PM 16942779 ER PT J AU Bogner, P Capua, I Cox, NJ Lipman, DJ AF Bogner, Peter Capua, Ilaria Cox, Nancy J. Lipman, David J. TI A global initiative on sharing avian flu data SO NATURE LA English DT Letter C1 Bogner Org, Santa Monica, CA 90403 USA. Ist Zooprofilatt Sperimentale Venezie, OFFLU OIE FAO Network, Sci Comm, I-35020 Padua, Italy. Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Bogner, P (reprint author), Bogner Org, 927 15th St, Santa Monica, CA 90403 USA. NR 3 TC 47 Z9 49 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 31 PY 2006 VL 442 IS 7106 BP 981 EP 981 DI 10.1038/442981a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 078YF UT WOS:000240142000024 ER PT J AU Bertagnolli, MM Eagle, CJ Zauber, AG Redston, M Solomon, SD Kim, KM Tang, J Rosenstein, RB Wittes, J Corle, D Hess, TM Woloj, GM Boisserie, F Anderson, WF Viner, JL Bagheri, D Burn, J Chung, DC Dewar, T Foley, TR Hoffman, N Macrae, F Pruitt, RE Saltzman, JR Salzberg, B Sylwestrowicz, T Gordon, GB Hawk, ET AF Bertagnolli, Monica M. Eagle, Craig J. Zauber, Ann G. Redston, Mark Solomon, Scott D. Kim, KyungMann Tang, Jie Rosenstein, Rebecca B. Wittes, Janet Corle, Donald Hess, Timothy M. Woloj, G. Mabel Boisserie, Frederic Anderson, William F. Viner, Jaye L. Bagheri, Donya Burn, John Chung, Daniel C. Dewar, Thomas Foley, T. Raymond Hoffman, Neville Macrae, Finlay Pruitt, Ronald E. Saltzman, John R. Salzberg, Bruce Sylwestrowicz, Thomas Gordon, Gary B. Hawk, Ernest T. CA APC Study Investigators TI Celecoxib for the prevention of sporadic colorectal adenomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HIGH-FIBER DIET; RANDOMIZED-TRIAL; VITAMIN-D; LOW-FAT; CANCER; RECURRENCE; ASPIRIN; SUPPLEMENTATION; POLYPS; RISK AB Background: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. Methods: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. Results: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P < 0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P < 0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). Conclusions: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. C1 Brigham & Womens Hosp, Div Surg Oncol, Boston, MA 02115 USA. Pfizer, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Wisconsin, Madison, WI USA. Stat Collaborat, Washington, DC USA. NCI, Bethesda, MD 20892 USA. CCS Associates, Mountain View, CA USA. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harris Methodist Hosp Ft Worth, Ft Worth, TX USA. Reg Gastroenterol Associates Lancaster, Lancaster, PA USA. Sir Charles Gairdner Hosp, Perth, WA, Australia. Royal Melbourne Hosp, Melbourne, Vic, Australia. Nashville Med Res Inst, Nashville, TN USA. Atlanta Gastroenterol Associates, Atlanta, GA USA. Univ Saskatchewan, St Pauls Hosp, Saskatoon, SK, Canada. GD Searle & Co, Skokie, IL 60077 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, Div Surg Oncol, 75 Francis St, Boston, MA 02115 USA. EM mbertagnolli@partners.org RI Solomon, Scott/I-5789-2013; Zavoral, Miroslav/D-9174-2017 OI Zavoral, Miroslav/0000-0001-7883-7431 FU NCI NIH HHS [N01-CN-95015] NR 25 TC 626 Z9 645 U1 2 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 31 PY 2006 VL 355 IS 9 BP 873 EP 884 DI 10.1056/NEJMoa061355 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 078OM UT WOS:000240113100005 PM 16943400 ER PT J AU White, JD Smits, H Hamel, E AF White, James D. Smits, Helmars Hamel, Ernest TI Synthesis of cryptothilone 1, the first cryptophycin-epothilone hybrid SO ORGANIC LETTERS LA English DT Article ID CONFORMATIONAL-ANALYSIS; ARENASTATIN; ESTERIFICATION; GSV-224; ANALOGS AB A hybrid structure was synthesized in which one portion is characteristic of a cryptophycin and a second sector bears the signature of an epothilone. The hybrid, in contrast to parent cryptophycin and epothilone systems, showed no effect on the tubulin assembly reaction. C1 Oregon State Univ, Dept Chem, Corvallis, OR 97331 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Ft Detrick, MD 21702 USA. RP White, JD (reprint author), Oregon State Univ, Dept Chem, Gilbert Hall 153, Corvallis, OR 97331 USA. EM james.white@oregonstate.edu FU NIGMS NIH HHS [GM 50574] NR 22 TC 10 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD AUG 31 PY 2006 VL 8 IS 18 BP 3947 EP 3950 DI 10.1021/ol0614020 PG 4 WC Chemistry, Organic SC Chemistry GA 076XE UT WOS:000239990900015 PM 16928045 ER PT J AU Moscicki, AB Schiffman, M Kjaer, S Villa, LL AF Moscicki, Anna-Barbara Schiffman, Mark Kjaer, Susanne Villa, Luisa L. TI Updating the natural history of HPV and anogenital cancer SO VACCINE LA English DT Article DE natural history; HPV; anogenital cancer ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL INTRAEPITHELIAL NEOPLASIA; COSTA-RICA; CHLAMYDIA-TRACHOMATIS; ADOLESCENT WOMEN; IMMUNE-RESPONSES; POSITIVE WOMEN; ABSOLUTE RISK; YOUNG-WOMEN; CONDOM USE AB The major steps in cervical carcinogenesis include infection of the metaplastic epithelium of the cervical transformation zone with one or more of the 12-18 carcinogenic types of human papillomavirus (HPV) infection, viral persistence, clonal progression of the persistently-infected epithelium to cervical precancer, and invasion. Although these fundamental steps are established, several new epidemiologic studies have shed light on the factors that influence each of these transitions. The importance of the transformation zone in cervical cancer has been extended to other HPV-induced cancers such as anal or tonsillar cancers. Natural history studies show that HPV with normal cervical cytology and cervical intraepithelial neoplasia (CIN) grade I behave similarly, with the majority of both showing regression. Although these studies have demonstrated the importance of HPV persistence in the development of precancer CIN-3, the timing from infection to evidence of CIN-3 varies from I to 10 years. Whether equivalent lesions diagnosed later differ in their natural history remains unknown. Several factors have been implicated in enhancing persistence and/or progression. However, none are consistently associated with both except age: young women are less likely to show persistence and older women with persistence are more likely to be at risk of invasive cancer. Recent studies have also underscored the importance of the host immune response in clearance of established infections. Finally, data on non-cervical HPV infections, such as penile infections are limited to date compared to cervical infections. Several ongoing cohort studies should give us further insight into mate infections in the near future. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, Dept Pediat, Div Adolescent Med, San Francisco, CA 94143 USA. NCI, Hormonoal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD USA. Inct Canc Epidemiol, Copenhagen, Denmark. Ludwig Inst Canc Res, Dept Virol, Sao Paulo, Brazil. RP Moscicki, AB (reprint author), Univ Calif San Francisco, Dept Pediat, Div Adolescent Med, 3333 Calif Ave Suite 245, San Francisco, CA 94143 USA. EM moscickia@peds.ucsf.edu NR 45 TC 128 Z9 137 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 42 EP 51 DI 10.1016/j.vaccine.2006.06.018 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000007 ER PT J AU Kitchener, HC Castle, PE Cox, JT AF Kitchener, Henry C. Castle, Philip E. Cox, J. Thomas TI Achievements and limitations of cervical cytology screening SO VACCINE LA English DT Article DE cervical; screening; cytology ID SQUAMOUS INTRAEPITHELIAL LESIONS; HUMAN-PAPILLOMAVIRUS; UNDETERMINED SIGNIFICANCE; MANAGEMENT STRATEGIES; CONTROLLED-TRIAL; SMEAR TEST; FOLLOW-UP; CANCER; WOMEN; RISK AB This chapter reviews the contribution of cervical cytology, what makes it successful, the management of screen positives and how technological advances may affect its use in the future. Cervical screening has saved hundreds of thousands of lives but has not been available to women in the poorest countries. In countries where wide coverage has been achieved and quality assurance is in place, incidence and death rates have fallen by over 50% even though cervical cytology is logistically complex. The management of high-grade cervical intraepithelial neoplasia (CIN) is very effective, but low-grade cytological abnormalities require care to avoid over-treatment. The increasing rate of human papillomavirus (HPV) testing and the prospect of prophylactic vaccination will change the way cervical cytology is used, possibly giving way to HPV testing as the primary test in secondary prevention. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Manchester, St Marys Hosp, Unit Obstet & Gynaecol, Manchester M13 0JH, Lancs, England. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Calif Santa Barbara, Gynecol Clin, Hlth Serv, Santa Barbara, CA 93106 USA. RP Kitchener, HC (reprint author), Univ Manchester, St Marys Hosp, Unit Obstet & Gynaecol, Whitworth Pk, Manchester M13 0JH, Lancs, England. EM henry.kitchener@cmmc.nhs.uk NR 34 TC 67 Z9 72 U1 4 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 63 EP 70 DI 10.1016/j.vaccine.2006.05.113 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000009 ER PT J AU Stanley, M Lowy, DR Frazer, I AF Stanley, Margaret Lowy, Douglas R. Frazer, Ian TI Prophylactic HPV vaccines: Underlying mechanisms SO VACCINE LA English DT Article DE HPV; L1 VLP vaccines; neutralising antibody; immune correlates; genotype replacement; protection; epitope mapping; cross-protection ID VIRUS-LIKE PARTICLES; HUMAN-PAPILLOMAVIRUS TYPE-16; COTTONTAIL RABBIT PAPILLOMAVIRUS; RANDOMIZED CONTROLLED-TRIAL; NEUTRALIZING ANTIBODIES; YOUNG-WOMEN; INFECTION; EPITOPES; EFFICACY; IMMUNOGENICITY AB Human papillomavirus virus-like particles (HPV VLP) can be generated by the synthesis and self-assembly in vitro of the major virus capsid protein L1. HPV L1 VLPs are morphologically and antigenically almost identical to native virions, and this technology has been exploited to produce HPV L1 VLP subunit vaccines. The vaccines elicit high titres of anti-L I VLP antibodies that persist at levels 10 times that of natural infections for at least 48 months. At present the assumption is that the protection achieved by these vaccines against incident HPV infection and HPV-associated ano-genital pathology is mediated via serum neutralising Immunoglobulin G (IgG). However, since there have been very few vaccine failures thus far, immune correlates of protection have not been established. The available evidence is that the immunodominant neutralising antibodies generated by L1 VLPs are type-specific and are not cross-neutralising, although highly homologous HPV pairs share minor cross-neutralisation epitopes. Important issues remaining to be addressed include the duration of protection and genotype replacement. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. Natl Canc Inst, Cellular Oncol Lab, Bethesda, MD USA. Univ Queensland, Ctr Immunol & Canc Res, St Lucia, Qld 4067, Australia. RP Stanley, M (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM mas1001@cam.ac.uk NR 32 TC 77 Z9 86 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 106 EP 113 DI 10.1016/j.vaccine.2006.05.110 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000014 ER PT J AU Schiller, JT Nardelli-Haefliger, D AF Schiller, John T. Nardelli-Haefliger, Denise TI Second generation HPV vaccines to prevent cervical cancer SO VACCINE LA English DT Article DE prophylactic vaccines; therapeutic vaccines; DNA vaccines; bacterial vectors; viral vectors; mucosal vaccines ID VIRUS-LIKE PARTICLES; IMMUNE-RESPONSES; DELIVERY-SYSTEMS; PAPILLOMAVIRUS TYPES; HEALTHY-VOLUNTEERS; ESCHERICHIA-COLI; PROTEIN VACCINE; L1 PROTEIN; RECOMBINANT; MUCOSAL AB Prophylactic human papillomavirus (HPV) vaccines based on intramuscular injection of non-infectious L1 virus-like particles (VLPs) are undergoing intense clinical evaluation. As documented in preceding chapters of this monograph, clinical trials of these vaccines have demonstrated their safety and high efficacy at preventing type-specific persistent cervical HPV infection and the development of type-specific cervical intraepithelial neoplasia (CIN) cervical neoplasia. There is widespread optimism that VLP vaccines will become commercially available within the next few years. The prospects for development of alternative HPV vaccines must be considered in light of the likelihood that a safe and effective prophylactic HPV vaccine will soon be available. Three questions need to be addressed: (1) Is there sufficient need for a second generation vaccine? (2) Are there sufficiently attractive candidates for clinical trials? (3) Is there a realistic development/commericialization path? Published by Elsevier Ltd. C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. CHU Vaudois, Inst Microbiol, CH-1011 Lausanne, Switzerland. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov NR 35 TC 23 Z9 24 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 147 EP 153 DI 10.1016/j.vaccine.2006.05.123 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000019 ER PT J AU Franco, EL Cuzick, J Hildesheim, A de Sanjose, S AF Franco, Eduardo L. Cuzick, Jack Hildesheim, Allan de Sanjose, Silvia TI Issues in planning cervical cancer screening in the era of HPV vaccination SO VACCINE LA English DT Article DE cervical cancer; HPV; vaccines; screening; cytology; prevention ID HUMAN-PAPILLOMAVIRUS TYPE-16; RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; CYTOLOGIC ABNORMALITIES; YOUNG-WOMEN; FOLLOW-UP; EFFICACY; PRECURSORS; PROGRAMS; HEALTH AB uHuman Papillomavirus (HPV) vaccines will likely have an impact as a preventive strategy for cervical cancer. Screening for precancerous lesions cannot be discontinued because vaccination will not protect against HPV types not included in the first generation of vaccines. Moreover, protection for the target types, 16 and 18, which are responsible for most cases of cervical precancerous lesions and cancer, and 6 and 11, which are responsible for a substantial proportion of low-grade lesions, cannot be expected to be absolute, and the likely implementation of HPV vaccination in young women will not impact older groups initially. Cervical cancer control programs will need to be re-evaluated because the addition of HPV vaccination will make the existing approach of high-frequency screening by cytology too costly and inefficient for most public health budgets. Simply making cytology screening less frequent may not be a viable strategy in light of potential problems that may plague cytology performance in conditions of low lesion prevalence. HPV testing has the performance characteristics that would make it an ideal primary screening test in such conditions. Cytology should be reserved for triage of HPV-positive cases because it is more likely to perform with sufficient accuracy in high-prevalence conditions. Another advantage of using HPV testing as a primary screening tool is the opportunity to create infection registries that can link test results from the same women over time, thus allowing an efficient and low-cost strategy to monitor long-term protection among vaccinated women. (c) 2006 Elsevier Ltd. All rights reserved. C1 McGill Univ, Dept Oncol, Div Canc Epidemiol, Montreal, PQ H2W 1S6, Canada. McGill Univ, Dept Epidemiol & Biostat, Div Canc Epidemiol, Montreal, PQ H2W 1S6, Canada. Canc Res UK, Ctr Epidemiol Mathemat & Stat, Wolfson Inst Prevent Med, London, England. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. IDIBELL, Canc Epidemiol & Registrat Unit, Inst Catala Oncol, Barcelona, Spain. RP Franco, EL (reprint author), McGill Univ, Dept Oncol, Div Canc Epidemiol, 546 Pine Ave W, Montreal, PQ H2W 1S6, Canada. EM eduardo.franco@mcgill.ca RI de Sanjose Llongueras, Silvia/H-6339-2014; OI Franco, Eduardo/0000-0002-4409-8084 NR 21 TC 65 Z9 67 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 171 EP 177 DI 10.1016/j.vaccine.2006.05.061 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000022 ER PT J AU Hildesheim, A Markowitz, L Avila, MH Franceschi, S AF Hildesheim, Allan Markowitz, Lauri Avila, Mauricio Hernandez Franceschi, Silvia TI Research needs following initial licensure of virus-like particle HPV vaccines SO VACCINE LA English DT Article DE human papillomavirus; post-licensure; vaccine; evaluation; review ID CANCER; EFFICACY; NEOPLASIA; TRIALS; SAFETY AB Human papillomavirus virus-like particle (HPV VLP) HPV vaccines currently evaluated for licensing are likely to be available soon. Licensure will be based on evidence that the vaccine is well tolerated and provides near complete type-specific protection against HPV infections and their resulting lesions in the first few years after vaccination. Several important questions will remain to be answered after licensure to guide vaccine implementation and to permit the rational evaluation of vaccination in cancer prevention programs. These include the long-term safety and efficacy of vaccination, the optimal ages for vaccination, efficacy against HPV types not included in the vaccine and against existing infections, and efficacy in males. Modulators of vaccine efficacy (e.g., HIV infection) and immune mechanisms of long-term protection also remain to be defined. The real-world effectiveness of vaccination programs will need to be assessed. Issues related to the implementation of a vaccine that targets pre-adolescents and early adolescents and to the acceptability of a cancer vaccine targeted against a sexually transmitted infection will need to be understood before vaccination programs can be successful. It is hoped that continued improvements to the current HPV vaccines will lead to the introduction in future years of second generation vaccines that simplify delivery and/or expand its coverage. Finally, the natural history of HPV types not covered in the candidate vaccines will need to be carefully studied following vaccination. Public health authorities in various countries will play a pivotal role in determining if these questions are answered in a timely manner. Published by Elsevier Ltd. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Ctr Dis Control & Prevent, Div STD Prevent, Atlanta, GA USA. Inst Nacl Salud Publ, Ctr Invest Salud Poblac, Cuernavaca, Morelos, Mexico. Int Agcy Res Canc, Infect & Canc Epidemiol Grp, F-69372 Lyon, France. RP Hildesheim, A (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7062, Rockville, MD USA. EM hildesha@exchange.nih.gov NR 15 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 227 EP 232 DI 10.1016/j.vaccine.2006.05.102 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000029 ER PT J AU Franco, EL Bosch, FX Cuzick, J Schiller, JT Garnett, GP Meheus, A Wright, TC AF Franco, Eduardo L. Bosch, F. Xavier Cuzick, Jack Schiller, John T. Garnett, Geoffrey P. Meheus, Andre Wright, Thomas C. TI Knowledge gaps and priorities for research on prevention of HPV infection and cervical cancer SO VACCINE LA English DT Article DE cervical cancer; human papillomavirus; vaccine; screening; cytology; prevention; health economics; models AB The recognition that human papillomavirus (HPV) infection is the necessary cause of cervical cancer brought new prevention paradigms in screening and HPV immunization. We now face many questions about how to implement an ambitious evidence-based agenda for cervical cancer prevention. Much is known about the epidemiology and natural history of HPV infection but several key variables remain to be elucidated. Research on HPV transmission requires new study designs to provide useful insights into preventive strategies. HPV testing has carved a niche in clinical practice but to consolidate its role in screening still requires evidence of long-term benefit. The rapidly evolving field of HPV diagnostics has contributed useful information concerning the value of HPV typing. Other screening methods hold promise in specific settings. The decade-long process that brought HPV vaccines to the doorstep of public health application is over. Many questions remain concerning long-term efficacy, correlates of protection, age of vaccination, and delivery. As vaccination makes inroads as a cancer control strategy, screening practices must be reformulated to maximize the synergy between primary and secondary prevention. Research on how to achieve an efficient combination of these modalities is yet to begin, but mathematical models have provided a useful road map for field-testing of promising algorithms. Daunting questions loom large concerning delivery of vaccines to those populations that need it the most. The field of HPV and cervical cancer prevention has never been so multi-disciplinary. A new era has begun and the challenges are many. (c) 2006 Elsevier Ltd. All rights reserved. C1 McGill Univ, Div Canc Epidemiol, Dept Oncol, Montreal, PQ H2W 1S6, Canada. McGill Univ, Div Canc Epidemiol, Dept Epidemiol & Biostat, Montreal, PQ H2W 1S6, Canada. IBIDELL, Canc Epidemiol & Registry Unit, Inst Catala Oncol, Barcelona, Spain. Canc Res UK, Ctr Epidemiol Math & Stat, Wolfson Inst Prevent Med, London, England. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England. Univ Antwerp, Dept Epidemiol & Social Med, B-2020 Antwerp, Belgium. Columbia Univ, Dept Pathol, New York, NY USA. RP Franco, EL (reprint author), McGill Univ, Div Canc Epidemiol, Dept Oncol, 546 Pine Ave W, Montreal, PQ H2W 1S6, Canada. EM eduardo.franco@mcgill.ca RI Garnett, Geoffrey/A-9312-2008; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012; OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Franco, Eduardo/0000-0002-4409-8084 NR 3 TC 8 Z9 9 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 242 EP 249 DI 10.1016/j.vaccine.2006.06.038 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000031 ER PT J AU Wright, TC Bosch, FX Franco, EL Cuzick, J Schiller, JT Garnett, GP Meheus, A AF Wright, Thomas C. Bosch, F. Xavier Franco, Eduardo L. Cuzick, Jack Schiller, John T. Garnett, Geoffrey P. Meheus, Andre TI HPV vaccines and screening in the prevention of cervical cancer; conclusions from a 2006 workshop of international experts SO VACCINE LA English DT Article DE cervical cancer; human papillomavirus; vaccine; screening; cytology; prevention; health economics; models ID HUMAN-PAPILLOMAVIRUS INFECTION; RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; YOUNG-WOMEN; FOLLOW-UP; EFFICACY; TYPE-18; LESIONS; RISK; METAANALYSIS AB The finding that cervical cancer only occurs in women infected with specific, "high-risk" types of the human papillomavirus (HPV) has led to the development of novel, non-cytology-based cervical cancer prevention strategies. We now have sensitive molecular methods for detecting HPV that dramatically improve our ability to detect high-grade cervical cancer precursor lesions. Perhaps more importantly, prophylactic HPV vaccines have been developed that are protective against cervical cancer precursors caused by HPV 16 and 18. In the Spring of 2006, over 100 experts in HPV, cervical cancer screening, and vaccination worked together to define how best to incorporate HPV DNA testing and the HPV vaccines into cervical cancer prevention efforts. In this summary, we summarize the opinions of this expert group on how these advances can be introduced to provide the maximum benefit to women and to reduce the global burden of cervical cancer. (c) 2006 Published by Elsevier Ltd. C1 Columbia Univ, Dept Pathol, New York, NY 10032 USA. IDIBELL, Canc Epidemiol & Registry Unit, Inst Catala Oncol, Barcelona, Spain. McGill Univ, Dept Oncol, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ H3A 2T5, Canada. Canc Res UK, Ctr Epidemiol Math & Stat, Wolfson Inst Prevent Med, London, England. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis Epidemiol, London, England. Univ Antwerp, Dept Epidemiol & Social Med, B-2020 Antwerp, Belgium. RP Wright, TC (reprint author), Columbia Univ, Dept Pathol, Room 16-404,P&S Bldg,630 W 168th St, New York, NY 10032 USA. EM tcw1@columbia.edu RI Garnett, Geoffrey/A-9312-2008; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012 OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412 NR 46 TC 23 Z9 25 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 31 PY 2006 VL 24 SU 3 BP 251 EP 261 DI 10.1016/j.vaccine.2006.06.064 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 083PF UT WOS:000240470000032 ER PT J AU Yu, X Munge, B Patel, V Jensen, G Bhirde, A Gong, JD Kim, SN Gillespie, J Gutkind, JS Papadimitrakopoulos, F Rusling, JF AF Yu, Xin Munge, Bernard Patel, Vyomesh Jensen, Gary Bhirde, Ashwin Gong, Joseph D. Kim, Sang N. Gillespie, John Gutkind, J. Silvio Papadimitrakopoulos, Fotios Rusling, James F. TI Carbon nanotube amplification strategies for highly sensitive immunodetection of cancer biomarkers SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; LASER CAPTURE MICRODISSECTION; ELECTROCHEMICAL DETECTION; ANALYTICAL PERFORMANCE; SYSTEMS BIOLOGY; HEALTH-CARE; IMMUNOASSAY; FUNCTIONALIZATION; IMMUNOSENSORS; PEROXIDASE AB We describe herein the combination of electrochemical immunosensors using single-wall carbon nanotube (SWNT) forest platforms with multi-label secondary antibody-nanotube bioconjugates for highly sensitive detection of a cancer biomarker in serum and tissue lysates. Greatly amplified sensitivity was attained by using bioconjugates featuring horseradish peroxidase (HRP) labels and secondary antibodies (Ab(2)) linked to carbon nanotubes (CNT) at high HRP/Ab(2) ratio. This approach provided a detection limit of 4 pg mL(-1) (100 amol mL(-1)), for prostate specific antigen (PSA) in 10 mu L of undiluted calf serum, a mass detection limit of 40 fg. Accurate detection of PSA in human serum samples was demonstrated by comparison to standard ELISA assays. PSA was quantitatively measured in prostate tissue samples for which PSA could not be differentiated by the gold standard immunohistochemical staining method. These easily fabricated SWNT immunosensors show excellent promise for clinical screening of cancer biomarkers and point-of-care diagnostics. C1 Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06032 USA. Salve Regina Univ, Dept Chem, Newport, RI 02840 USA. Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 USA. NCI, Pathogenet Unit, Ctr Adv Technol, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Rusling, JF (reprint author), Univ Connecticut, Dept Chem, 55 N Eagleville Rd, Storrs, CT 06269 USA. EM james.rusling@uconn.edu RI Gutkind, J. Silvio/A-1053-2009 FU Intramural NIH HHS; NIEHS NIH HHS [ES013557, R01 ES013557, R01 ES013557-01A2] NR 43 TC 466 Z9 478 U1 27 U2 177 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 30 PY 2006 VL 128 IS 34 BP 11199 EP 11205 AR JA062117E DI 10.1021/ja062117e PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 076BR UT WOS:000239932500049 PM 16925438 ER PT J AU Igarashi, H Ito, T Yoshinaga, M Sakai, H Muto, Y Takayanagi, R Coy, DH Jensen, RT AF Igarashi, Hisato Ito, Tetsuhide Yoshinaga, Masahiro Sakai, Hironori Muto, Yoichi Takayanagi, Ryoichi Coy, David H. Jensen, Robert T. TI Elucidation of the VIP pharmacophore for human VPAC1 and VPAC2 and development of simplified VIP analogs with receptor selectivity and stability SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 16th International Symposium on Regulatory Peptides CY AUG 31-SEP 02, 2006 CL Hakone, JAPAN C1 Beppu Med Ctr, Div Gastroenterol, Beppu, Oita, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan. Tulane Univ, Ctr Hlth Sci, Peptide Res Labs, Dept Med, New Orleans, LA 70118 USA. NIDDK, NIH, Digest Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 30 PY 2006 VL 135 IS 3 BP 131 EP 131 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 083ZB UT WOS:000240499800071 ER PT J AU Vaudry, D Ravni, A Au, R Chan, P Piquenot, J Chow, B Fournier, A Vaudry, H Eiden, LE AF Vaudry, D. Ravni, A. Au, R. Chan, P. Piquenot, J. Chow, B. Fournier, A. Vaudry, H. Eiden, L. E. TI The PC12 cell line as a model to identify genes involved in the neurotrophic activities of PACAP SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 16th International Symposium on Regulatory Peptides CY AUG 31-SEP 02, 2006 CL Hakone, JAPAN C1 Univ Rouen, INSERM, U413, IFRMP 23, F-76821 Mont St Aignan, France. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. INRS, IAF, Pointe Claire, PQ, Canada. NIMH, Mol Neurosci Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 30 PY 2006 VL 135 IS 3 BP 166 EP 167 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 083ZB UT WOS:000240499800177 ER PT J AU Vaudry, D Bourgault, S Botia, B Galas, L Raoult, E Jolivel, V Basille, M Aubert, N Benard, M Eiden, LE Komuro, H Gonzalez, BJ Fournier, A Vaudry, H AF Vaudry, D. Bourgault, S. Botia, B. Galas, L. Raoult, E. Jolivel, V Basille, M. Aubert, N. Benard, M. Eiden, L. E. Komuro, H. Gonzalez, B. J. Fournier, A. Vaudry, H. TI PACAP: from neurodevelopment to neuroprotection SO REGULATORY PEPTIDES LA English DT Meeting Abstract CT 16th International Symposium on Regulatory Peptides CY AUG 31-SEP 02, 2006 CL Hakone, JAPAN C1 Univ Rouen, INSERM, U413, IFRMP 23, F-76821 Mont St Aignan, France. INRS, IAF, Pointe Claire, PQ, Canada. CIT, Evreux, France. NIMH, Mol Neurosci Sect, Bethesda, MD 20892 USA. Lerner Res Inst, Cleveland, OH USA. RI galas, ludovic/A-2500-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD AUG 30 PY 2006 VL 135 IS 3 BP 191 EP 191 PG 1 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 083ZB UT WOS:000240499800192 ER PT J AU Shaw, LJ Merz, NB Pepine, CJ Reis, SE Bittner, V Kip, KE Kelsey, SF Olson, M Johnson, BD Mankad, S Sharaf, BL Rogers, WJ Pohost, GM Sopko, G AF Shaw, Leslee J. Merz, Noel Bairey Pepine, Carl J. Reis, Steven E. Bittner, Vera Kip, Kevin E. Kelsey, Sheryl F. Olson, Marian Johnson, B. Delia Mankad, Sunil Sharaf, Barry L. Rogers, William J. Pohost, Gerald M. Sopko, George CA WISE Investigators TI The economic burden of angina in women with suspected ischemic heart disease - Results from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation SO CIRCULATION LA English DT Article DE coronary disease; angina; women; angiography; cost-benefit analysis; prognosis ID SYNDROME EVALUATION WISE; FUTURE-RESEARCH DIRECTIONS; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR MEDICINE; FUNCTIONAL-CAPACITY; COST-EFFECTIVENESS; OCTOBER 2-4; CHEST-PAIN; GENDER; CARE AB Background-Coronary angiography is one of the most frequently performed procedures in women; however, nonobstructive (ie, < 50% stenosis) coronary artery disease (CAD) is frequently reported. Few data exist regarding the type and intensity of resource consumption in women with chest pain after coronary angiography. Methods and Results -A total of 883 women referred for coronary angiography were prospectively enrolled in the National Institutes of Health -National Heart, Lung, and Blood Institute -sponsored Women's Ischemia Syndrome Evaluation (WISE). Cardiovascular prognosis and cost data were collected. Direct (hospitalizations, office visits, procedures, and drug utilization) and indirect (out-of-pocket, lost productivity, and travel) costs were estimated through 5 years of follow-up. Among 883 women, 62%, 17%, 11%, and 10% had nonobstructive and 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Five-year cardiovascular death or myocardial infarction rates ranged from 4% to 38% for women with nonobstructive to 3-vessel CAD (P < 0.0001). Five-year rates of hospitalization for chest pain occurred in 20% of women with nonobstructive CAD, increasing to 38% to 55% for women with 1-vessel to 3-vessel CAD (P < 0.0001). The volume of repeat catheterizations or angina hospitalizations was 1.8-fold higher in women with nonobstructive versus 1-vessel CAD after 1 year of follow-up (P < 0.0001). Drug treatment was highest for those with nonobstructive or 1-vessel CAD (P < 0.0001). The proportion of costs for anti-ischemic therapy was higher for women with nonobstructive CAD (15% versus 12% for 1-vessel to 3-vessel CAD; P = 0.001). For women with nonobstructive CAD, average lifetime cost estimates were $ 767 288 (95% CI, $ 708 480 to $ 826 097) and ranged from $ 1 001 493 to $ 1 051 302 for women with 1-vessel to 3-vessel CAD (P = 0.0003). Conclusions -Symptom-driven care is costly even for women with nonobstructive CAD. Our lifetime estimates for costs of cardiovascular care identify a significant subset of women who are unaccounted for within current estimates of the economic burden of coronary heart disease. C1 Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL 32611 USA. Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Allegheny Univ Hlth Sci, Dept Med, Div Cardiol, Pittsburgh, PA USA. Rhode Isl Hosp, Div Cardiol, Providence, RI 02903 USA. Univ Alabama Birmingham, Dept Med, Div Cardiovasc Dis, Birmingham, AL USA. Univ So Calif, Div Cardiol, Los Angeles, CA 90089 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Suite 1-N,1256 Briarcliff Rd NE, Atlanta, GA 30306 USA. EM leslee.shaw@emory.edu RI Reis, Steven/J-3957-2014; OI Bittner, Vera/0000-0001-9456-850X FU NCRR NIH HHS [MO1-RR00425]; NHLBI NIH HHS [N01-HV-68162, N01-HV-68161, N01-HV-68163, N01-HV-68164, U01 HL649141, U01 HL649241]; PHS HHS [U0164829] NR 47 TC 112 Z9 115 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD AUG 29 PY 2006 VL 114 IS 9 BP 894 EP 904 DI 10.1161/CIRCULATIONAHA.105.609990 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 078BI UT WOS:000240075700005 PM 16923752 ER PT J AU Esser, L Gong, X Yang, SQ Yu, L Yu, CA Xia, D AF Esser, Lothar Gong, Xing Yang, Shaoqing Yu, Linda Yu, Chang-An Xia, Di TI Surface-modulated motion switch: Capture and release of iron-sulfur protein in the cytochrome bc(1) complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE crystal structures; electron transfer; inhibitor binding; mechanism ID UBIQUINOL OXIDATION; ELECTRON-TRANSFER; BOVINE HEART; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; DOMAIN MOVEMENT; SITE INHIBITORS; BINDING; SPHAEROIDES; OXIDOREDUCTASE AB In the cytochrome bc(1) complex, the swivel motion of the iron-sulfur protein (ISP) between two redox sites constitutes a key component of the mechanism that achieves the separation of the two electrons in a substrate molecule at the quinol oxidation (Q(0)) site. The question remaining is how the motion of ISP is controlled so that only one electron enters the thermodynamically favorable chain via ISP. An analysis of eight structures of mitochondrial bc(1) with bound Q(0) site inhibitors revealed that the presence of inhibitors causes a bidirectional repositioning of the cd1 helix in the cytochrome b subunit. As the cd1 helix forms a major part of the ISP binding crater, any positional shift of this helix modulates the ability of cytochrome b to bind ISP. The analysis also suggests a mechanism for reversal of the ISP fixation when the shape complementarity is significantly reduced after a positional reorientation of the reaction product quinone. The importance of shape complementarity in this mechanism was confirmed by functional studies of bc(1) mutants and by a structure determination of the bacterial form of bc(1). A mechanism for the high fidelity of the bifurcated electron transfer is proposed. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. RP Yu, CA (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Bldg 37,Room 2122C, Bethesda, MD 20892 USA. EM cayuq@okstate.edu; dixia@helix.nih.gov RI yang, shaoqing/C-9761-2012 FU Intramural NIH HHS; NIGMS NIH HHS [GM 30721, R01 GM030721, R37 GM030721] NR 32 TC 68 Z9 84 U1 2 U2 10 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 AUG 29 PY 2006 VL 103 IS 35 BP 13045 EP 13050 DI 10.1073/pnas.0601149103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 082IU UT WOS:000240380800020 PM 16924113 ER PT J AU Mulkidjanian, AY Koonin, EV Makarova, KS Mekhedov, SL Sorokin, A Wolf, YI Dufresne, A Partensky, F Burd, H Kaznadzey, D Haselkorn, R Galperin, MY AF Mulkidjanian, Armen Y. Koonin, Eugene V. Makarova, Kira S. Mekhedov, Sergey L. Sorokin, Alexander Wolf, Yuri I. Dufresne, Alexis Partensky, Frederic Burd, Henry Kaznadzey, Denis Haselkorn, Robert Galperin, Michael Y. TI The cyanobacterial genome core and the origin of photosynthesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cyanobacteria; protein families; lateral gene transfer ID SYNECHOCYSTIS SP PCC-6803; SEQUENCE-ANALYSIS; EARLY EVOLUTION; PHOTOSYSTEM-I; OXYGENIC PHOTOSYNTHESIS; HELIOBACILLUS-MOBILIS; SULFUR METABOLISM; PURPLE BACTERIA; GENE-CLUSTER; EARLY-LIFE AB Comparative analysis of 15 complete cyanobacterial genome sequences, including "near minimal" genomes of five strains of Prochlorococcus spp., revealed 1,054 protein families [core cyanobacterial clusters of orthologous groups of proteins (core CyOGs)] encoded in at least 14 of them. The majority of the core CyOGs are involved in central cellular functions that are shared with other bacteria; 50 core CyOGs are specific for cyanobacteria, whereas 84 are exclusively shared by cyanobacteria and plants and/or other plastid-carrying eukaryotes, such as diatoms or apicomplexans. The latter group includes 35 families of uncharacterized proteins, which could also be involved in photosynthesis. Only a few components of cyanobacterial photosynthetic machinery are represented in the genomes of the anoxygenic phototrophic bacteria Chlorobium tepidum, Rhodopseudomonas palustris, Chloroflexus aurantiacus, or Heliobacillus mobilis. These observations, coupled with recent geological data on the properties of the ancient phototrophs, suggest that photosynthesis originated in the cyanobacterial lineage under the selective pressures of UV light and depletion of electron donors. We propose that the first phototrophs were anaerobic ancestors of cyanobacteria ("procyanobacteria") that conducted anoxygenic photosynthesis using a photosystem I-like reaction center, somewhat similar to the heterocysts of modern filamentous cyanobacteria. From procyanobacteria, photosynthesis spread to other phyla by way of lateral gene transfer. C1 Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. Moscow MV Lomonosov State Univ, AN Belozersky Inst PhysicoChem Biol, Moscow 119899, Russia. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. CNRS, Biol Stn, UMR 7144, F-29682 Roscoff, France. Univ Paris 06, F-29682 Roscoff, France. Integrated Genom Inc, Chicago, IL 60612 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de; r-haselkorn@uchicago.edu; galperin@ncbi.nim.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013; OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064; Dufresne, Alexis/0000-0001-8231-9098; Partensky, Frederic/0000-0003-1274-4050 FU Intramural NIH HHS [Z99 LM999999] NR 70 TC 148 Z9 154 U1 0 U2 36 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 AUG 29 PY 2006 VL 103 IS 35 BP 13126 EP 13131 DI 10.1073/pnas.0605709103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 082IU UT WOS:000240380800034 PM 16924101 ER PT J AU Ohta, A Gorelik, E Prasad, SJ Ronchese, F Lukashev, D Wong, MKK Huang, XJ Caldwell, S Liu, KB Smith, P Chen, JF Jackson, EK Apasov, S Abrams, S Sitkovsky, M AF Ohta, Akio Gorelik, Elieser Prasad, Simon J. Ronchese, Franca Lukashev, Dmitriy Wong, Michael K. K. Huang, Xiaojun Caldwell, Sheila Liu, Kebin Smith, Patrick Chen, Jiang-Fan Jackson, Edwin K. Apasov, Sergey Abrams, Scott Sitkovsky, Michail TI A2A adenosine receptor protects tumors from antitumor T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; cancer; therapy; hypoxia; inflammation ID INFILTRATING LYMPHOCYTES; ANTIGEN-4 BLOCKADE; CANCER REGRESSION; DEFICIENT MICE; IFN-GAMMA; IN-VIVO; MELANOMA; EXPRESSION; REVEALS; INHIBITION AB The A2A adenosine receptor (A2AR) has been shown to be a critical and nonredundant negative regulator of immune cells in protecting normal tissues from inflammatory damage. We hypothesized that A2AR also protects cancerous tissues by inhibiting incoming antitumor T lymphocytes. Here we confirm this hypothesis by showing that genetic deletion of A2AR in the host resulted in rejection of established immunogenic tumors in approximate to 60% of A2AR-deficient mice with no rejection observed in control WT mice. The use of antagonists, including caffeine, or targeting the A2 receptors by siRNA pretreatment of T cells improved the inhibition of tumor growth, destruction of metastases, and prevention of neovascularization by antitumor T cells. The data suggest that effects of A2AR are T cell autonomous. The inhibition of antitumor T cells via their A2AR in the adenosine-rich tumor microenvironment may explain the paradoxical coexistence of tumors and antitumor immune cells in some cancer patients (the "Hellstrom paradox"). We propose to target the hypoxia -> adenosine -> ASAR pathway as a cancer immumotherapy strategy to prevent the inhibition of antitumor T cells in the tumor microenvironment. The same strategy may prevent the premature termination of immune response and improve the vaccine-induced development of antitumor and antiviral T cells. The observations of autoimmunity during melanoma rejection in A2AR-deficient mice suggest that A2AR in T cells is also important in preventing autoimmunity. Thus, although using the hypoxia -> adenosine -> A2AR pathway inhibitors may improve antitumor immunity, the recruitment of this pathway by selective drugs is expected to attenuate the autoimmune tissue damage. C1 Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Malaghan Inst Med Res, Wellington, New Zealand. Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Univ Pittsburgh, Inst Canc, Ctr Clin Pharmacol, Univ Pittsburgh Canc Inst,Dept Pharmacol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Ctr Clin Pharmacol, Univ Pittsburgh Canc Inst,Dept Med, Pittsburgh, PA 15213 USA. RP Sitkovsky, M (reprint author), Northeastern Univ, New England Inflammat & Tissue Protect Inst, 360 Huntington Ave,113 Mugar Life Sci Bldg, Boston, MA 02115 USA. EM m.sitkovsky@neu.edu RI Lukashev, Dmitriy/F-8133-2010; OI Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS; NCI NIH HHS [1 R01 CA112561 1-NIH, R01 CA112561] NR 46 TC 276 Z9 279 U1 2 U2 29 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 AUG 29 PY 2006 VL 103 IS 35 BP 13132 EP 13137 DI 10.1073/pnas.0605251103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 082IU UT WOS:000240380800035 PM 16916931 ER PT J AU Atkins, KA Jeronimo, J Stoler, MH AF Atkins, Kristen A. Jeronimo, Jose Stoler, Mark H. CA ALTS Grp TI Description of patients with squamous cell carcinoma in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intralepithelial Lesion Triage Study SO CANCER CYTOPATHOLOGY LA English DT Article DE squamous cell carcinoma; cervical cancer; Atypical Squamous cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study; atypical squamous cells of undetermined significance; low-grade squamous intraepithelial lesion ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ASCUS-LSIL TRIAGE; HUMAN-PAPILLOMAVIRUS; MANAGEMENT STRATEGIES; CYTOLOGY; WOMEN AB BACKGROUND. The Atypical Squamous Cells of Undetermined Significance/LowGrade Squamous Intraepithelial Lesion Triage Study (ALTS) accumulated information regarding conventional and liquid-based Papanicolaou (Pap) cytology, 2 kinds of human papillomavirus (HPV) DNA testing, cervicography, and colposcopically directed biopsy. The prevalence of squamous cell carcinoma in these women, the efficacy of tests, and the time to detection were reviewed. METHODS. The ALTS data base was reviewed for all women with invasive carcinoma. All results of colposcopy, HPV testing, cytology, biopsies, and cervigrams were reviewed for all women in the ALTS trial who were diagnosed with squamous cell carcinoma. RESULTS. There were 7 diagnoses of invasive cancer (all squamous cell) during the 2 years of the ALTS trial. Although the enrollment studies isolated many high-grade lesions, none of those results were diagnostic of the underlying carcinoma. CONCLUSIONS. The prevalence of squamous cell carcinoma in the setting of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion cytology interpretation appears to be low (approximately I per 1000 women in the ALTS trial). Many of the carcinomas were not visible on the ectocervix by cervicography or colposcopy, which may explain in part the paucity of atypical cells detected on the Pap tests and the finding that the presenting cytology, although abnormal, was never diagnostic of cancer. HPV DNA tests were positive in all 7 cancers. Type-specific testing identified HPV type 16 in 6 of 7 cancers and HPV type 18 in I of 7 cancers. Cancer (Cancer Cytopathol) 2006; 108:212-21. (c) 2006 American Cancer Society. C1 Univ Virginia Hlth Syst, Dept Pathol, Charlottesville, VA 22908 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. RP Atkins, KA (reprint author), Univ Virginia Hlth Syst, Dept Pathol, 1215 Lee St,Off 3028, Charlottesville, VA 22908 USA. EM kaa2p@virginia.edu FU NCI NIH HHS [CN-55159, CN-55154, CN-55156, CN-55158, CN-55152, CN-55105, CN-55157, CN-55155] NR 16 TC 12 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD AUG 25 PY 2006 VL 108 IS 4 BP 212 EP 221 DI 10.1002/cncr.21940 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 076IB UT WOS:000239949200003 PM 16680733 ER PT J AU Even-Ram, S Artym, V Yamada, KM AF Even-Ram, Sharona Artym, Vira Yamada, Kenneth M. TI Matrix control of stem cell fate SO CELL LA English DT Editorial Material ID MORPHOGENESIS C1 NIH, Craniofacial Dev Biol & Regenerat Branch, Natl Inst Dental & Craniofacial Res, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. RP Yamada, KM (reprint author), NIH, Craniofacial Dev Biol & Regenerat Branch, Natl Inst Dental & Craniofacial Res, Bldg 10, Bethesda, MD 20892 USA. EM kyamada@mail.nih.gov OI Even-Ram, Sharona/0000-0002-5540-3822; Yamada, Kenneth/0000-0003-1512-6805 NR 9 TC 112 Z9 116 U1 3 U2 32 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 25 PY 2006 VL 126 IS 4 BP 645 EP 647 DI 10.1016/j.cell.2006.08.008 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 080VN UT WOS:000240276700010 PM 16923382 ER PT J AU Sakamoto, K Ito, Y Mori, T Sugimura, K AF Sakamoto, Kotaro Ito, Yuji Mori, Toshiyuki Sugimura, Kazuhisa TI Interaction of human lactoferrin with cell adhesion molecules through RGD motif elucidated by lactoferrin-binding epitopes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSFERRIN RECEPTOR; PROTEIN; LIPOPOLYSACCHARIDE; ANGIOGENESIS; ACTIVATION; COMPLEX; CLONING; ARG(4); FAMILY AB Lactoferrin (LF) is an iron-binding secretory protein, which is distributed in the secondary granules of polynuclear lymphocytes as well as in the milk produced by female mammals. Although it has multiple functions, for example antimicrobial, immunomodulatory, antiviral, and anti-tumor metastasis activities, the receptors responsible for these activities are not fully understood. In this study, the binding epitopes for human LF were first isolated from a hexameric random peptide library displayed on T7 phage. Interestingly, two of the four isolated peptides had a representative cell adhesion motif, Arg-Gly-Asp (RGD), implying that human LF interacts with proteins with the RGD motif. We found that human LF bound to the RGD-containing human extracellular matrix proteins, fibronectin and vitronectin. Furthermore, human LF inhibited cell adhesion to these matrix proteins in a concentration-dependent manner but not to the RGD-independent cell adhesion molecule like laminin or collagen. These results indicate that a function of human LF is to block the various interactions between the cell surface and adhesion molecules. This may explain the multifunctionality of LF. C1 Kagoshima Univ, Fac Engn, Kagoshima 8900065, Japan. NCI, Mol Targets Dev Program, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Ito, Y (reprint author), Kagoshima Univ, Fac Engn, Kagoshima 8900065, Japan. EM yito@be.kagoshima-u.ac.jp FU Intramural NIH HHS NR 24 TC 28 Z9 29 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24472 EP 24478 DI 10.1074/jbc.M604974200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800042 PM 16787913 ER PT J AU Bhattacharyya, N Pechhold, K Shahjee, H Zappala, G Elbi, C Raaka, B Wiench, M Hong, J Rechler, MM AF Bhattacharyya, Nisan Pechhold, Klaus Shahjee, Hanief Zappala, Giovanna Elbi, Cem Raaka, Bruce Wiench, Malgorzata Hong, Jiang Rechler, Matthew M. TI Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; HORMONE-RELATED PEPTIDE; TGF-BETA RECEPTOR; FACTOR-I; SURFACE BINDING; LUNG-CANCER; FACTOR BINDING-PROTEIN-3; TARGETED DISRUPTION; CELLULAR GROWTH; INHIBITION AB Insulin-like growth factor binding protein-3 (IGFBP-3), a secreted protein, has the intrinsic ability to induce apoptosis directly without binding insulin-like growth factors. Previous studies suggested that IGFBP-3 must be secreted to exert its biological functions. IGFBP-3 contains a nuclear localization signal (NLS), and exogenous IGFBP-3 is translocated into the nucleus, suggesting that both secretion and nuclear localization may play important roles in IGFBP-3 action. To address these questions, we fused yellow fluorescent protein (YFP) to mature IGFBP-3 lacking its signal peptide so that it would remain intracellular and mutated the C-terminal NLS of IGFBP-3, 228KGRKR232, to MDGEA. Following transfection of PC-3 human prostate cancer cells with these constructs, Western blots indicated that YFP-IGFBP-3 lacking a signal peptide was cell-associated and not present in the extracellular media. Moreover, the fusion protein was not N- glycosylated, indicating that it had not entered the secretory pathway. Confocal imaging showed that intracellular YFP-MDGEA-IGFBP-3 was predominantly cytoplasmic. Transient transfection of nonsecreted YFP-wild-type IGFBP-3 decreased cell viability, as assessed by staining with annexin V followed by flow cytometry. Induction of cell death was caspase-dependent, indicative of apoptosis. Apoptosis also was induced by the nonsecreted NLS mutant (YFP-MDGEA-IGFBP-3) alone and when the IGF-binding site also had been mutated. These results indicate that IGFBP-3 can induce apoptosis in an IGF-independent manner without being secreted or concentrated in the nucleus. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Islet Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Rechler, MM (reprint author), NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM mrechler@helix.nih.gov FU Intramural NIH HHS NR 86 TC 48 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24588 EP 24601 DI 10.1074/jbc.M509463200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800054 PM 16793770 ER PT J AU Guo, MX Wang, D Shao, HJ Qiu, HL Xue, L Zhao, ZZ Zhu, CG Shi, YB Li, WX AF Guo, Ming-Xiong Wang, Di Shao, Huan-Jie Qiu, Hong-Ling Xue, Lu Zhao, Zhou-Zhou Zhu, Chen-Gang Shi, Yun-Bo Li, Wen-Xin TI Transcription of human zinc finger ZNF268 gene requires an intragenic promoter element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-PROTEIN; CANDIDATE GENE; NUCLEAR FACTOR; HUMAN EMBRYO; CYCLIC-AMP; DNA; CREB; LEUKEMIA; IDENTIFICATION; CAMP AB Human ZNF268 gene is a typical Kruppel-associated box/C2H2 zinc finger gene whose homolog has been found only in higher mammals and not in lower mammals such as mouse. Its expression profiles have suggested that it plays a role in the differentiation of blood cells during early human embryonic development and the pathogenesis of leukemia. To gain additional insight into the molecular mechanisms controlling the expression of the ZNF268 gene and to provide the necessary tools for further genetic studies of leukemia, we have mapped the 5'-end of the human ZNF268 mRNA by reverse transcription-PCR and primer extension assays. We then cloned the 5'-flanking genomic-DNA-containing the putative ZNF268 gene promoter and analyzed its function in several different human and mouse tissue culture cell lines. Interestingly, our studies show that the ZNF268 gene lacks a typical eukaryotic promoter that is present upstream of the transcription start site and directs a basal level of transcription. Instead, the functional promoter requires an essential element that is located within the first exon of the gene. Deletion and mutational analysis reveals the requirement for a cAMP response-element-binding protein (CREB)-binding site within this element for promoter function. Gel mobility shift and chromatin immunoprecipitation assays confirm that CREB-2 binds to the site in vitro and in vivo. Furthermore, overexpression of CREB-2 enhances the promoter activity. These results demonstrate that the human ZNF268 gene promoter is atypical and requires an intragenic element located within the first exon that mediates the effect of CREB for its activity. C1 Wuhan Univ, Coll Life Sci, State Key Virol, Wuhan 430072, Peoples R China. NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Li, WX (reprint author), Wuhan Univ, Coll Life Sci, State Key Virol, Wuhan 430072, Peoples R China. EM Liwxlab@whu.edu.cn RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 NR 54 TC 14 Z9 18 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24623 EP 24636 DI 10.1074/jbc.M602753200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800057 PM 16787922 ER PT J AU Jana, SS Kawamoto, S Adelstein, RS AF Jana, Siddhartha S. Kawamoto, Sachiyo Adelstein, Robert S. TI A specific isoform of nonmuscle myosin II-C is required for cytokinesis in a tumor cell line SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RHO-DEPENDENT KINASE; HEAVY-CHAIN ISOFORMS; CLEAVAGE FURROW; EXPRESSION; GENE; CLONING; PHOSPHORYLATION; IDENTIFICATION; SEQUENCES; ADHESION AB Nonmuscle myosin IIs play an essential role during cytokinesis. Here, we explore the function of an alternatively spliced isoform of nonmuscle myosin heavy chain(NMHC) II-C, called NMHCII-C1, in the A549 human lung tumor cell line during cytokinesis. NMHC II-C1 contains an insert of 8 amino acids in the head region of NMHCII-C. First, we show that there is a marked increase in both the mRNA encoding NMHC II-C1 and protein in tumor cell lines compared with nontumor cell lines derived from the same tissue. Quantification of the amount of myosin II isoforms in the A549 cells shows that the amounts of NMHCII-A and II-C1 protein are about equal and substantially greater than NMHCII-B. Using specific siRNAs to decrease NMHC II-C1 in cultured A549 cells resulted in a 5.5-fold decrease in the number of cells at 120 h, whereas decreasing NMHC II-A with siRNA does not affect cell proliferation. This decreased proliferation can be rescued by reintroducing NMHCII-C1 but not NMHCII-A or II-B into A549 cells, although noninserted NMHCII-C does rescue to a limited extent. Time lapse video microscopy revealed that loss of NMHC II-C1 leads to a delay in cytokinesis and prolongs it from 2 to 8-10 h. These findings are consistent with the localization of NMHCII-C1 to the intercellular bridge that attaches the two dividing cells during the late phases of cytokinesis. The results suggest a specific function for NMHC II-C1 in cytokinesis in the A549 tumor cell line. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. EM adelster@nhlbi.nih.gov OI Adelstein, Robert/0000-0002-8683-2144 NR 37 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24662 EP 24670 DI 10.1074/jbc.M604606200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800061 PM 16790446 ER PT J AU Wally, J Halbrooks, PJ Vonrhein, C Rould, MA Everse, SJ Mason, AB Buchanan, SK AF Wally, Jeremy Halbrooks, Peter J. Vonrhein, Clemens Rould, Mark A. Everse, Stephen J. Mason, Anne B. Buchanan, Susan K. TI The crystal structure of iron-free human serum transferrin provides insight into inter-lobe communication and receptor binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED CONFORMATIONAL-CHANGE; CARBOXYL-TERMINAL LOBES; PH-SENSITIVE TRIAD; N-LOBE; C-LOBE; ANION-BINDING; ANGSTROM RESOLUTION; HEN OVOTRANSFERRIN; DUCK OVOTRANSFERRIN; MUTATIONAL ANALYSIS AB Serum transferrin reversibly binds iron in each of two lobes and delivers it to cells by a receptor-mediated, pH-dependent process. The binding and release of iron result in a large conformational change in which two subdomains in each lobe close or open with a rigid twisting motion around a hinge. We report the structure of human serum transferrin (hTF) lacking iron (apo-hTF), which was independently determined by two methods: 1) the crystal structure of recombinant non-glycosylated apo-hTF was solved at 2.7-angstrom resolution using a multiple wavelength anomalous dispersion phasing strategy, by substituting the nine methionines in hTF with selenomethionine and 2) the structure of glycosylated apo-hTF (isolated from serum) was determined to a resolution of 2.7 angstrom by molecular replacement using the human apo-N-lobe and the rabbit holo-C1-subdomain as search models. These two crystal structures are essentially identical. They represent the first published model for full-length human transferrin and reveal that, in contrast to family members (human lactoferrin and hen ovotransferrin), both lobes are almost equally open: 59.4 degrees and 49.5 degrees rotations are required to open the N- and C-lobes, respectively (compared with closed pig TF). Availability of this structure is critical to a complete understanding of the metal binding properties of each lobe of hTF; the apo-hTF structure suggests that differences in the hinge regions of the N- and C-lobes may influence the rates of iron binding and release. In addition, we evaluate potential interactions between apo-hTF and the human transferrin receptor. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Global Phasing Ltd, Cambridge CB3 0AX, England. Univ Vermont, Coll Med, Dept Mol Physiol & Biophys, Burlington, VT 05405 USA. RP Buchanan, SK (reprint author), NIDDK, Mol Biol Lab, NIH, 50 S Dr,Rm 4503, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK021739, R01 DK21739, Z01 DK011003-04] NR 89 TC 120 Z9 121 U1 4 U2 20 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24934 EP 24944 DI 10.1074/jbc.M604592200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800086 PM 16793765 ER PT J AU Mercer, JC DeHaven, WI Smyth, JT Wedel, B Boyles, RR Bird, GS Putney, JW AF Mercer, Jason C. DeHaven, Wayne I. Smyth, Jeremy T. Wedel, Barbara Boyles, Rebecca R. Bird, Gary S. Putney, James W., Jr. TI Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHANNEL FUNCTION; PLASMA-MEMBRANE; CA2+ INFLUX; ARACHIDONIC-ACID; PORE PROPERTIES; ENTRY; RELEASE; CELLS; CRAC; POTENTIATION AB The molecular nature of store-operated Ca2+-selective channels has remained an enigma, due largely to the continued inability to convincingly demonstrate Ca2+-selective store-operated currents resulting from exogenous expression of known genes. Recent findings have implicated two proteins, Stim1 and Orai1, as having essential roles in store-operated Ca2+ entry across the plasma membrane. However, transient overexpression of these proteins on their own results in little or no increase in store-operated entry. Here we demonstrate dramatic synergism between these two mediators; co-transfection of HEK293 cells with Stim1 and Orai1 results in an approximate 20-fold increase in store-operated Ca2+ entry and Ca2+-selective current. This demonstrates that these two proteins are limiting for both the signaling and permeation mechanisms for Ca2+-selective store-operated Ca2+ entry. There are three mammalian homologs of Orai1, and in expression experiments they all produced or augmented store-operated Ca2+ entry with efficacies in the order Orai1 > Orai2 > Orai3. Stim1 apparently initiates the signaling process by acting as a Ca2+ sensor in the endoplasmic reticulum. This results in rearrangement of Stim1 within the cell and migration toward the plasma membrane to regulate in some manner Orai1 located in the plasma membrane. However, we demonstrate that Stim1 does not incorporate in the surface membrane, and thus likely regulates or interacts with Orai1 at sites of close apposition between the plasma membrane and an intracellular Stim1-containing organelle. C1 NIEHS, NIH, Lab Signal Transduct, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, Lab Signal Transduct, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov OI Boyles, Rebecca/0000-0003-0073-6854 FU Intramural NIH HHS [Z99 ES999999] NR 37 TC 338 Z9 357 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 25 PY 2006 VL 281 IS 34 BP 24979 EP 24990 DI 10.1074/jbc.M604589200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074YF UT WOS:000239847800090 PM 16807233 ER PT J AU Strober, W AF Strober, Warren TI Unraveling gut inflammation SO SCIENCE LA English DT Editorial Material ID BOWEL-DISEASE; CELLS; DEFENSINS; INTESTINE; BACTERIA C1 NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIH, Host Def Lab, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 14 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 25 PY 2006 VL 313 IS 5790 BP 1052 EP 1054 DI 10.1126/science.1131997 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076ZT UT WOS:000239998200024 PM 16931742 ER PT J AU Klar, AJS Armakolas, A AF Klar, Amar J. S. Armakolas, Athanasios TI Response to comment on "Cell type regulates selective segregation of mouse chromosome 7 DNA strands in mitosis" SO SCIENCE LA English DT Editorial Material AB To explain how all chromosome recombinants can become homozygous for a marker located distal to the crossover point, we proposed that mitotic recombination must be restricted to two specific chromatids and that the selective chromatid segregation process follows recombination. We refute Haber's contention that our results can be explained by the conventional X-segregation process if recombination of all possible combinations of chromatids is considered. C1 Natl Canc Inst, Lab Gene Express & Choromsome Biol, Frederick, MD 21702 USA. Hippokraeteion Hosp Athens, Surg Res Lab, Athens 11527, Greece. RP Klar, AJS (reprint author), Natl Canc Inst, Lab Gene Express & Choromsome Biol, POB B, Frederick, MD 21702 USA. EM klar@ncifcrf.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 25 PY 2006 VL 313 IS 5790 DI 10.1126/science.1128552 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076ZT UT WOS:000239998200054 ER PT J AU Nagarajan, M Morrell, A Antony, S Kohlhagen, G Agama, K Pommier, Y Ragazzon, PA Garbett, NC Chaires, JB Hollingshead, M Cushman, M AF Nagarajan, Muthukaman Morrell, Andrew Antony, Smitha Kohlhagen, Glenda Agama, Keli Pommier, Yves Ragazzon, Patricia A. Garbett, Nichola C. Chaires, Jonathan B. Hollingshead, Melinda Cushman, Mark TI Synthesis and biological evaluation of bisindenoisoquinolines as topoisomerase I inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID POTENTIAL ANTITUMOR AGENTS; DNA-BINDING PROPERTIES; BIFUNCTIONAL INTERCALATORS; COVALENT COMPLEX; DIACRIDINES; CAMPTOTHECIN; MECHANISM; CELLS; TOPOTECAN; DIMERS AB The indenoisoquinolines represent a class of non-camptothecin topoisomerase I (Top1) inhibitors that exert cytotoxicity by trapping the covalent complex formed between DNA and Top1 during relaxation of DNA supercoils. As an ongoing evaluation of Top1 inhibition and anticancer activity, indenoisoquinolines were linked via their lactam side chains to provide polyamines end-capped with intercalating motifs. The resulting bisindenoisoquinolines were evaluated for cytotoxicity in the National Cancer Institute's human cancer cell screen and for Top1 inhibition. Preliminary findings suggested that the 2-3-2and 3-3-3 linkers, referring to the number of carbons between nitrogen atoms, were optimal for both potent Top1 inhibition and cytotoxicity. Using optimized linkers, bisindenoisoquinolines were synthesized with nitro and methoxy substituents on the aromatic rings. The biological results for substituted compounds revealed a disagreement between the structure-activity relationships of monomeric indenoisoquinolines and bisindenoisoquinolines as Top1 inhibitors, but cytotoxicity was maintained for both series of compounds. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmcol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. Ctr Canc Res, Lab Mol Pharmacol, NCI, Bethesda, MD 20892 USA. Univ Louisville, Hlth Sci Ctr, Dept Med, James Graham Brown Canc Ctr, Louisville, KY 40202 USA. NCI, Div Canc Treatment & Diagnost, Dev Therapeut Program, Biol Testing Branch,Fairview Ctr,NIH, Frederick, MD 21701 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmcol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu OI Ragazzon, Patricia/0000-0003-0374-4569 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, ST32 CA09634-12, U01 CA89566]; PHS HHS [C06-14499] NR 48 TC 30 Z9 31 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 24 PY 2006 VL 49 IS 17 BP 5129 EP 5140 DI 10.1021/jm060046o PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 074ND UT WOS:000239818200010 PM 16913702 ER PT J AU Ghosh, AK Sridhar, PR Leshchenko, S Hussain, AK Li, JF Kovalevsky, AY Walters, DE Wedekind, JE Grum-Tokars, V Das, D Koh, Y Maeda, K Gatanaga, H Weber, IT Mitsuya, H AF Ghosh, Arun K. Sridhar, Perali Ramu Leshchenko, Sofiya Hussain, Azhar K. Li, Jianfeng Kovalevsky, Andrey Yu. Walters, D. Eric Wedekind, Joseph E. Grum-Tokars, Valerie Das, Debananda Koh, Yasuhiro Maeda, Kenji Gatanaga, Hiroyuki Weber, Irene T. Mitsuya, Hiroaki TI Structure-based design of novel HIV-1 protease inhibitors to combat drug resistance SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 PROTEASE; RESOLUTION CRYSTAL-STRUCTURES; ACTIVE-SITE; DERIVATIVES; MECHANISMS; MUTATIONS; DISCOVERY; SELECTION; INSIGHTS; TMC114 AB Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino) sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b] furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 angstrom resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance. C1 Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. Georgia State Univ, Dept Biol Mol Basis Dis, Atlanta, GA 30303 USA. Rosalind Franklin Univ Med & Sci, Dept Biochem & Mol Biol, Abbott Pk, IL 60064 USA. Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan. Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu RI Walters, D. Eric/C-9626-2010; Li, Jianfeng/F-5057-2014; OI Walters, D. Eric/0000-0002-1513-3522; Li, Jianfeng/0000-0002-8838-3872; Kovalevsky, Andrey/0000-0003-4459-9142 FU Intramural NIH HHS; NIGMS NIH HHS [GM62920, R01 GM062920, GM 53386] NR 41 TC 73 Z9 75 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 24 PY 2006 VL 49 IS 17 BP 5252 EP 5261 DI 10.1021/jm060561m PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 074ND UT WOS:000239818200022 PM 16913714 ER PT J AU Martin, W Koonin, EV AF Martin, William Koonin, Eugene V. TI A positive definition of prokaryotes SO NATURE LA English DT Letter C1 Univ Dusseldorf, Inst Bot, D-40225 Dusseldorf, Germany. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Martin, W (reprint author), Univ Dusseldorf, Inst Bot, D-40225 Dusseldorf, Germany. RI Martin, William/C-5680-2008; Martin, William /O-5446-2015 OI Martin, William /0000-0003-1478-6449 NR 4 TC 23 Z9 24 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 24 PY 2006 VL 442 IS 7105 BP 868 EP 868 DI 10.1038/442868c PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076LT UT WOS:000239960500015 PM 16929275 ER PT J AU Schlacher, K Cox, MM Woodgate, R Goodman, MF AF Schlacher, Katharina Cox, Michael M. Woodgate, Roger Goodman, Myron F. TI RecA acts in trans to allow replication of damaged DNA by DNA polymerase V SO NATURE LA English DT Article ID ESCHERICHIA-COLI; TRANSLESION SYNTHESIS; BIOCHEMICAL BASIS; UV-MUTAGENESIS; LESION BYPASS; IN-VITRO; POL V; PROTEIN; COMPLEX; REPAIR AB The DNA polymerase V (pol V) and RecA proteins are essential components of a mutagenic translesion synthesis pathway in Escherichia coli designed to cope with DNA damage. Previously, it has been assumed that RecA binds to the DNA template strand being copied. Here we show, however, that pol-V-catalysed translesion synthesis, in the presence or absence of the beta-processivity-clamp, occurs only when RecA nucleoprotein filaments assemble or RecA protomers bind on separate single-stranded ( ss) DNA molecules in trans. A 3'-proximal RecA filament end on trans DNA is essential for stimulation; however, synthesis is strengthened by further pol V - RecA interactions occurring elsewhere along a trans nucleoprotein filament. We suggest that trans-stimulation of pol V by RecA bound to ssDNA reflects a distinctive regulatory mechanism of mutation that resolves the paradox of RecA filaments assembled in cis on a damaged template strand obstructing translesion DNA synthesis despite the absolute requirement of RecA for SOS mutagenesis. C1 Univ So Calif, Dept Biol Sci & Chem, Los Angeles, CA 90089 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci & Chem, Univ Pk, Los Angeles, CA 90089 USA. EM mgoodman@usc.edu FU Intramural NIH HHS NR 31 TC 61 Z9 61 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 24 PY 2006 VL 442 IS 7105 BP 883 EP 887 DI 10.1038/nature05042 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076LT UT WOS:000239960500029 PM 16929290 ER PT J AU Huang, AL Chen, XK Hoon, MA Chandrashekar, J Guo, W Trankner, D Ryba, NJP Zuker, CS AF Huang, Angela L. Chen, Xiaoke Hoon, Mark A. Chandrashekar, Jayaram Guo, Wei Trankner, Dimitri Ryba, Nicholas J. P. Zuker, Charles S. TI The cells and logic for mammalian sour taste detection SO NATURE LA English DT Article ID RECEPTOR-CELLS; DIPHTHERIA-TOXIN; CELLULAR SENSORS; BITTER TASTE; UMAMI TASTE; SWEET; FAMILY; TRANSDUCTION; CHANNELS; NEURONS AB Mammals taste many compounds yet use a sensory palette consisting of only five basic taste modalities: sweet, bitter, sour, salty and umami ( the taste of monosodium glutamate)(1,2). Although this repertoire may seem modest, it provides animals with critical information about the nature and quality of food. Sour taste detection functions as an important sensory input to warn against the ingestion of acidic ( for example, spoiled or unripe) food sources(1-3). We have used a combination of bioinformatics, genetic and functional studies to identify PKD2L1, a polycystic-kidney-disease-like ion channel(4), as a candidate mammalian sour taste sensor. In the tongue, PKD2L1 is expressed in a subset of taste receptor cells distinct from those responsible for sweet, bitter and umami taste. To examine the role of PKD2L1-expressing taste cells in vivo, we engineered mice with targeted genetic ablations of selected populations of taste receptor cells. Animals lacking PKD2L1-expressing cells are completely devoid of taste responses to sour stimuli. Notably, responses to all other tastants remained unaffected, proving that the segregation of taste qualities even extends to ionic stimuli. Our results now establish independent cellular substrates for four of the five basic taste modalities, and support a comprehensive labelled-line mode of taste coding at the periphery(5-10). Notably, PKD2L1 is also expressed in specific neurons surrounding the central canal of the spinal cord. Here we demonstrate that these PKD2L1-expressing neurons send projections to the central canal, and selectively trigger action potentials in response to decreases in extracellular pH. We propose that these cells correspond to the long-sought components of the cerebrospinal fluid chemosensory system(11). Taken together, our results suggest a common basis for acid sensing in disparate physiological settings. C1 Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurobiol & Neurosci, La Jolla, CA 92093 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Zuker, CS (reprint author), Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. EM charles@flyeye.ucsd.edu RI chen, xiaoke/E-5385-2011 FU NIDCD NIH HHS [R01 DC004861] NR 31 TC 364 Z9 381 U1 18 U2 163 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 24 PY 2006 VL 442 IS 7105 BP 934 EP 938 DI 10.1038/nature05084 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076LT UT WOS:000239960500041 PM 16929298 ER PT J AU Jordan, IK Kondrashov, FA Adzhubei, IA Wolf, YI Koonin, EV Kondrashov, AS Sunyaev, S AF Jordan, I. K. Kondrashov, F. A. Adzhubei, I. A. Wolf, Y. I. Koonin, E. V. Kondrashov, A. S. Sunyaev, S. TI Causes of trends in amino-acid gain and loss - Reply SO NATURE LA English DT Letter ID PROTEIN EVOLUTION; HUMAN GENOME C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Calif Davis, Sect Evolut & Ecol, Davis, CA 95616 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. RP Jordan, IK (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM ssunyaev@rics.bwh.harvard.edu RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 8 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 24 PY 2006 VL 442 IS 7105 BP E12 EP E12 DI 10.1038/nature05138 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 076LT UT WOS:000239960500028 ER PT J AU Adams, KF Schatzkin, A Harris, TB Kipnis, V Mouw, T Ballard-Barbash, R Hollenbeck, A Leitzmann, MF AF Adams, Kenneth F. Schatzkin, Arthur Harris, Tamara B. Kipnis, Victor Mouw, Traci Ballard-Barbash, Rachel Hollenbeck, Albert Leitzmann, Michael F. TI Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BODY-MASS INDEX; MIDDLE-AGED MEN; EXCESS DEATHS; US ADULTS; FOLLOW-UP; WEIGHT; UNDERWEIGHT; GUIDELINES; ACCURACY; CANCER AB Background: Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. Methods: We prospectively examined BMI in relation to the risk of death from any cause in 527,265 U.S. men and women in the National Institutes of Health-AARP cohort who were 50 to 71 years old at enrollment in 1995-1996. BMI was calculated from self-reported weight and height. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. We also conducted alternative analyses to address potential biases related to preexisting chronic disease and smoking status. Results: During a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40 percent among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated. Conclusions: Excess body weight during midlife, including overweight, is associated with an increased risk of death. C1 NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. AARP, Washington, DC USA. RP Adams, KF (reprint author), Nutr Epidemiol Branch, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM adamske@mail.nih.gov FU Intramural NIH HHS NR 37 TC 1022 Z9 1047 U1 7 U2 73 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 24 PY 2006 VL 355 IS 8 BP 763 EP 778 DI 10.1056/NEJMoa055643 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 076KA UT WOS:000239955200005 PM 16926275 ER PT J AU Masumi, A Fukazawa, H Shimazu, T Yoshida, M Ozato, K Komuro, K Yamaguchi, K AF Masumi, A. Fukazawa, H. Shimazu, T. Yoshida, M. Ozato, K. Komuro, K. Yamaguchi, K. TI Nucleolin is involved in interferon regulatory factor-2-dependent transcriptional activation SO ONCOGENE LA English DT Article DE IRF-2; nucleolin; acetylation ID HISTONE ACETYLTRANSFERASES P300; H4 GENE-TRANSCRIPTION; HIV-1 TAT; P300/CBP-ASSOCIATED FACTOR; BINDING PROTEIN; ACETYLASE PCAF; FACTOR FAMILY; FACTOR IRF-2; DNA-BINDING; COMPLEX AB We have previously shown that interferon regulatory factor-2 (IRF-2) is acetylated in a cell growth-dependent manner, which enables it to contribute to the transcription of cell growth-regulated promoters. To clarify the function of acetylation of IRF-2, we investigated the proteins that associate with acetylated IRF-2. In 293T cells, the transfection of p300/CBP-associated factor (PCAF) enhanced the acetylation of IRF-2. In cells transfected with both IRF-2 and PCAF, IRF-2 associated with endogenous nucleolin, while in contrast, minimal association was observed when IRF-2 was transfected with a PCAF histone acetyl transferase (HAT) deletion mutant. In a pull-down experiment using stable transfectants, acetylation-defective mutant IRF-2 (IRF-2K75R) recruited nucleolin to a much lesser extent than wild-type IRF-2, suggesting that nucleolin preferentially associates with acetylated IRF-2. Nucleolin in the presence of PCAF enhanced IRF-2-dependent H4 promoter activity in NIH3T3 cells. Nucleolin knock-down using siRNA reduced the IRF-2/PCAF-mediated promoter activity. Chromatin immunoprecipitation analysis indicated that PCAF transfection increased nucleolin binding to IRF-2 bound to the H4 promoter. We conclude that nucleolin is recruited to acetylated IRF-2, thereby contributing to gene regulation crucial for the control of cell growth. C1 Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, Tokyo 2080011, Japan. Natl Inst Infect Dis, Dept Bioact Mol, Tokyo, Japan. RIKEN, Chem Genet Lab, Wako, Saitama, Japan. NICHHD, Lab Mol Growth & Regulat, NIH, Bethesda, MD 20892 USA. RP Masumi, A (reprint author), Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, 4-7-1,Gakuen, Tokyo 2080011, Japan. EM amasumi@nih.go.jp RI Yoshida, Minoru/C-8049-2014 NR 52 TC 24 Z9 24 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 24 PY 2006 VL 25 IS 37 BP 5113 EP 5124 DI 10.1038/sj.onc.1209522 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 077WZ UT WOS:000240063700004 PM 16582966 ER PT J AU Barsoum, MJ Yuan, H Gerencser, AA Liot, G Kushnareva, YE Graber, S Kovacs, I Lee, WD Waggoner, J Cui, JK White, AD Bossy, B Martinou, JC Youle, RJ Lipton, SA Ellisman, MH Perkins, GA Bossy-Wetzel, E AF Barsoum, Mark J. Yuan, Hua Gerencser, Akos A. Liot, Geraldine Kushnareva, Yulia E. Graeber, Simone Kovacs, Imre Lee, Wilson D. Waggoner, Jenna Cui, Jiankun White, Andrew D. Bossy, Blaise Martinou, Jean-Claude Youle, Richard J. Lipton, Stuart A. Ellisman, Mark H. Perkins, Guy A. Bossy-Wetzel, Ella TI Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons SO EMBO JOURNAL LA English DT Article DE Alzheimer's disease; dynamin related protein 1; mitofusin 1; Parkinson's disease; stroke ID CELL-DEATH; NEURODEGENERATIVE DISEASES; ULTRASTRUCTURAL-CHANGES; ELECTRON-TRANSPORT; S-NITROSYLATION; APOPTOSIS; PROTEIN; AUTOPHAGY; DIVISION; FUSION AB Mitochondria are present as tubular organelles in neuronal projections. Here, we report that mitochondria undergo profound fission in response to nitric oxide (NO) in cortical neurons of primary cultures. Mitochondrial fission by NO occurs long before neurite injury and neuronal cell death. Furthermore, fission is accompanied by ultrastructural damage of mitochondria, autophagy, ATP decline and generation of free radicals. Fission is occasionally asymmetric and can be reversible. Strikingly, mitochondrial fission is also an early event in ischemic stroke in vivo. Mitofusin 1 (Mfn1) or dominant-negative Dynamin related protein 1 (Drp1(K38A)) inhibits mitochondrial fission induced by NO, rotenone and Amyloid-beta peptide. Conversely, overexpression of Drp1 or Fis1 elicits fission and increases neuronal loss. Importantly, NO-induced neuronal cell death was mitigated by Mfn1 and Drp1(K38A). Thus, persistent mitochondrial fission may play a causal role in NO-mediated neurotoxicity. C1 Burnham Inst Med Res, Apoptosis & Cell Death Program, La Jolla, CA 92037 USA. Univ Calif San Francisco, Natl Ctr Microscopy & Imaging Res, Sch Med, La Jolla, CA USA. Univ Geneva, Dept Cell Biol, Geneva, Switzerland. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD USA. Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. RP Bossy-Wetzel, E (reprint author), Burnham Inst Med Res, Apoptosis & Cell Death Program, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ebossy-wetzel@burnham.org FU NCRR NIH HHS [P41 RR004050, P41RR04050]; NEI NIH HHS [R01 EY005477, R01 EY009024, R01 EY016164, R01 EY05477, R01 EY09024]; NIAID NIH HHS [P01 AI055789]; NICHD NIH HHS [P01 HD029587, P01 HD29587]; NINDS NIH HHS [R01 NS43242, R01 NS014718, R01 NS043242, R01 NS044314, R01 NS044326, R01 NS046994, R01 NS047456, R01 NS047456-S3, R01 NS047973, R01 NS14718, R01 NS44314] NR 55 TC 366 Z9 373 U1 0 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 23 PY 2006 VL 25 IS 16 BP 3900 EP 3911 DI 10.1038/sj.emboj.7601253 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 087SW UT WOS:000240763700017 PM 16874299 ER PT J AU Pearson, SD Miller, FG Emanuel, EJ AF Pearson, Steven D. Miller, Franklin G. Emanuel, Ezekiel J. TI Medicare's requirement for research participation as a condition of coverage - Is it ethical? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID QUALITY IMPROVEMENT; CLINICAL-RESEARCH; DECISION-MAKING; TRIALS; CRITERIA C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Pearson, SD (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118 6th Floor, Bethesda, MD 20892 USA. EM spearson99@yahoo.com NR 19 TC 35 Z9 35 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 23 PY 2006 VL 296 IS 8 BP 988 EP 991 DI 10.1001/jama.296.8.988 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 076AL UT WOS:000239929300029 PM 16926358 ER PT J AU Ban, H Yamamoto, H Fukunaga, M Nakagoshi, A Umeda, M Tanaka, C Ejima, Y AF Ban, Hiroshi Yamamoto, Hiroki Fukunaga, Masaki Nakagoshi, Asuka Umeda, Masahiro Tanaka, Chuzo Ejima, Yoshimichi TI Toward a common circle: Interhemispheric contextual modulation in human early visual areas SO JOURNAL OF NEUROSCIENCE LA English DT Article DE visual cortex; retinotopy; contextual modulation; interhemispheric integration; object/shape perception; fMRI ID FUNCTIONAL MRI; DISTINCT MODES; GLOBAL SHAPES; CORTEX V1; ORGANIZATION; VISION; REPRESENTATION; SYMMETRY; MONKEY; FIELD AB Humans can readily and effortlessly perceive a rich, stable, and unified visual world from a complex visual scene. Yet our internal representation of a visual object appears to be sparse and fragmented. How and where in the brain are such fragmented representations organized into a whole percept? Recent studies have accumulated evidence that some global feature integration is mediated at the early stage of visual processing. However, the spatial operating range of the integration still remains unclear. The present human functional magnetic resonance imaging study provides support that the global integration process in early visual areas, including even the primary visual area V1, is mediated beyond the separated projection of visual hemifields from right and left sides of the fixation to the visual cortex of the contralateral cerebral hemisphere. Retinotopic neural responses corresponding to a visual target were significantly enhanced when another target was simultaneously presented at the point-symmetrical position in the nonassociated visual field quadrant. The result makes a convincing case that the contextual effects involve feedback from higher areas, because there are no direct callosal connections that allow such interhemispheric contextual modulation. This enhancement from the ipsilateral hemifield may help rapid position-and-size-invariant detection of a circular pattern, which may be special among visual structures because of its ubiquity in natural scenes. Early visual areas as well as higher ones may play a more essential role in perceiving the unity of the real world than previously thought. C1 Kyoto Univ, Grad Sch Human & Environm Studies, Dept Cognit & Behav Sci, Sakyo Ku, Kyoto 6068501, Japan. Japan Soc Promot Sci, Tokyo 1028472, Japan. NIH, Lab Funct Mol Imaging, Bethesda, MD 20892 USA. Meiji Univ Oriental Med, Fac Med Informat, Kyoto 6290392, Japan. Kyoto Inst Technol, Kyoto 6068585, Japan. RP Ban, H (reprint author), Kyoto Univ, Grad Sch Human & Environm Studies, Dept Cognit & Behav Sci, Sakyo Ku, Yoshida Nihonmatsu Cho, Kyoto 6068501, Japan. EM ban@cv.jinkan.kyoto-u.ac.jp RI Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 29 TC 19 Z9 20 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 23 PY 2006 VL 26 IS 34 BP 8804 EP 8809 DI 10.1523/JNEUROSCI.1765-06.2006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 077CV UT WOS:000240006200018 PM 16928869 ER PT J AU Zhang, Y Qu, DB Morris, EJ O'Hare, MJ Callaghan, SM Slack, RS Geller, HM Park, DS AF Zhang, Yi Qu, Dianbo Morris, Erick J. O'Hare, Michael J. Callaghan, Steven M. Slack, Ruth S. Geller, Herbert M. Park, David S. TI The Chk1/Cdc25A pathway as activators of the cell cycle in neuronal death induced by camptothecin SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Chk1; Cdc25A; DNA damage; cell cycle; apoptosis; neurons ID DEPENDENT KINASE INHIBITORS; SINGLE-STRAND BREAKS; OXIDATIVE DNA-DAMAGE; TYROSINE PHOSPHATASE; ALZHEIMERS-DISEASE; SYMPATHETIC NEURONS; POSTMITOTIC NEURONS; PARKINSONS-DISEASE; CEREBRAL-ISCHEMIA; CORTICAL-NEURONS AB Cell cycle regulators appear to play a paradoxical role in neuronal death. We have shown previously that cyclin-dependent kinases (CDKs), along with their downstream effectors, Rb (retinoblastoma) and E2F/DP1 (E2 promoter binding factor/deleted in polyposis 1), regulate neuronal death evoked by the DNA damaging agent camptothecin. However, the mechanism by which CDKs are activated in this model is unclear. The cell division cycle 25A (Cdc25A) phosphatase is a critical regulator of cell cycle CDKs in proliferating cells. In cortical neurons, we presently show that expression of Cdc25A promotes death even in the absence of DNA damage. Importantly, Cdc25A activity is rapidly increased during DNA damage treatment. Inhibition of Cdc25A blocks death and reduces cyclin D1-associated kinase activity and Rb phosphorylation. This indicates that endogenous Cdc25A activity is important for regulation of cell cycle-mediated neuronal death. We also examined how Cdc25A activity is regulated after DNA damage. Cultured embryonic cortical neurons have a significant basal activity of checkpoint kinase 1 (Chk1), a kinase that regulates cell cycle arrest. During camptothecin treatment of neurons, this activity is rapidly downregulated with a concomitant increase in Cdc25A activity. Importantly, expression of wild-type Chk1, but not kinase-dead Chk1, inhibits the camptothecin-induced increase in Cdc25A activity. In addition, Chk1 expression also promotes survival in the presence of the DNA-damaging agent. Together, our data suggest that a Chk1/Cdc25A activity participates in activation of a cell cycle pathway-mediated death signal in neurons. These data also define how a proliferative signal may be abnormally activated in a postmitotic environment. C1 Univ Ottawa, Ottawa Hlth Res Inst, Neurosci Grp, Ottawa, ON K1H 8M5, Canada. NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. RP Park, DS (reprint author), Univ Ottawa, Ottawa Hlth Res Inst, Neurosci Grp, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM dpark@uottawa.ca RI Qu, Dianbo/C-5121-2011; OI Geller, Herbert/0000-0002-7048-6144 NR 81 TC 40 Z9 41 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 23 PY 2006 VL 26 IS 34 BP 8819 EP 8828 DI 10.1523/JNEUROSCI.2593-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 077CV UT WOS:000240006200020 PM 16928871 ER PT J AU Schmitz, S Smith-Palmer, J Sakamoto, T Sellers, JR Veigel, C AF Schmitz, Stephan Smith-Palmer, Jayne Sakamoto, Takeshi Sellers, James R. Veigel, Claudia TI Walking mechanism of the intracellular cargo transporter myosin V SO JOURNAL OF PHYSICS-CONDENSED MATTER LA English DT Article; Proceedings Paper CT Meeting on Molecular Nanomachines CY JAN 17-21, 2005 CL Les Houches, FRANCE ID HAND-OVER-HAND; LOAD-DEPENDENT KINETICS; PROCESSIVE MYOSIN; STEPPING KINETICS; OPTICAL TWEEZERS; STRUCTURAL BASIS; MUSCLE MYOSIN; NECK LENGTH; LEVER-ARM; MOTOR AB Motor proteins of the myosin, kinesin and dynein families transport vesicles and other cargo along tracks of actin filaments or microtubules through the cytoplasm of cells. The mechanism by which myosin V, a motor involved in several types of intracellular transport, moves processively along actin filaments, has recently been the subject of many single molecule biophysical studies. Details of the molecular mechanisms by which this molecular motor operates are starting to emerge. C1 Natl Inst Med Res, London NW7 1AA, England. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Schmitz, S (reprint author), Natl Inst Med Res, The Ridgeway,Mill Hill, London NW7 1AA, England. EM sschmit@nimr.mrc.ac.uk; sellersj@nhlbi.nih.gov; cveigel@nimr.mrc.ac.uk NR 57 TC 3 Z9 3 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0953-8984 J9 J PHYS-CONDENS MAT JI J. Phys.-Condes. Matter PD AUG 23 PY 2006 VL 18 IS 33 SI SI BP S1943 EP S1956 DI 10.1088/0953-8984/18/33/S12 PG 14 WC Physics, Condensed Matter SC Physics GA 070XD UT WOS:000239558800013 ER PT J AU Barlic, J Zhang, Y Foley, JF Murphy, PM AF Barlic, Jana Zhang, Yuan Foley, John F. Murphy, Philip M. TI Oxidized lipid-driven chemokine receptor switch, CCR2 to CX3CR1, mediates adhesion of human macrophages to coronary artery smooth muscle cells through a peroxisome proliferator-activated receptor gamma-dependent pathway SO CIRCULATION LA English DT Article DE atherosclerosis; lipids; leukocytes; receptors; signal transduction ID LOW-DENSITY-LIPOPROTEIN; FRACTALKINE CX3CL1; TNF-ALPHA; LESION FORMATION; GENE-EXPRESSION; MICE REVEALS; PPAR-GAMMA; DISEASE; ATHEROSCLEROSIS; MONOCYTES AB Background - Recent genetic data in mouse and humans suggest that the chemokine receptors CCR2 and CX3CR1 are involved in atherogenesis; however, detailed molecular and cellular mechanisms have not been fully delineated. Methods and Results - Here, we show that oxidized linoleic acid metabolites, which are components of oxidized LDL found in large amounts in atherosclerotic plaque, were able to specifically induce differentiation of human monocytes to macrophages with decreased expression of CCR2, confirming a previous report, and increased expression of CX3CR1. These macrophages acquired the ability to adhere to coronary artery smooth muscle cells. The adhesion was mediated directly and predominantly by CX3CR1. Reciprocal effects of these lipids on CCR2 and CX3CR1 expression were mediated by the nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma, and targeting the PPAR gamma gene with sRNAi dramatically reduced macrophage adhesion to coronary artery smooth muscle cells. Conclusions - These data suggest that in atherogenesis oxidized lipid-driven activation of macrophage PPAR gamma in the intima may result in a proadhesive chemokine receptor switch - CCR2 off, CX3CR1 on -causing cessation of CCR2-dependent migration and activation of CX3CR1-dependent retention mechanisms, which together promote macrophage accumulation in vessel wall. Our results may explain at the molecular and cell biology levels the genetic link between CX3CR1 and atherosclerosis. Moreover, they identify macrophage binding to coronary artery smooth muscle cells as the first primary cell setting in which CX3CR1 functions as the major adhesion system. C1 NIAID, Mol Signalling Sect, NIH, Bethesda, MD 20892 USA. NIAID, Inflammat Biol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signalling Sect, NIH, 9000 Rockvillel Pike,Blsg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov NR 42 TC 67 Z9 71 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 22 PY 2006 VL 114 IS 8 BP 807 EP 819 DI 10.1161/CIRCULATIONHA.105.602359 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 075XF UT WOS:000239920000012 PM 16908772 ER PT J AU Bidere, N Snow, AL Sakai, K Zheng, LX Lenardo, MJ AF Bidere, Nicolas Snow, Andrew L. Sakai, Keiko Zheng, Lixin Lenardo, Michael J. TI Caspase-8 regulation by direct interaction with TRAF6 in T cell receptor-induced NF-kappa B activation SO CURRENT BIOLOGY LA English DT Article ID LYMPHOCYTE-ACTIVATION; ANTIGEN RECEPTOR; IMMUNE-SYSTEM; CARMA1; PHOSPHORYLATION; TCR; PROTEIN; KINASE; DEATH; BCL10 AB Triggering of lymphocyte antigen receptors is the critical first step in the adaptive immune response against pathogens. T cell receptor (TCR) ligation assembles a large membrane signalosome, culminating in NF-kappa B activation [1, 2]. Recently, caspase-8 was found to play a surprisingly prominent role in lymphocyte activation in addition to its well-known role in apoptosis [3]. Caspase-8 is activated after TCR stimulation and nucleates a complex with B cell lymphoma 10 (BCL10), paracaspase MALT1, and the inhibitors of kappa B kinase (IKK) complex [4]. We now report that the ubiquitin ligase TRAF6 binds to active caspase-8 upon TCR stimulation and facilitates its movement into lipid rafts. We identified in silico two putative TRAF6 binding motifs in the caspase-8 sequence [5] and found that mutation of critical residues within these sites abolished TRAF6 binding and diminished TCR-induced NF-kappa B activation. Moreover, RNAi-mediated silencing of TRAF6 abrogated caspase-8 recruitment to the lipid rafts. Protein kinase C theta (PKC theta), CARMA1, and BCL10 are also required for TCR-induced caspase-8 relocation, but only PKC theta and BCL10 control caspase-8 activation. Our results suggest that PKC theta independently controls CARMA1 phosphorylation and BCL10-dependent caspase-8 activation and unveil an essential role for TRAF6 as a critical adaptor linking these two convergent signaling events. C1 NIAID, NIH, Mol Dev Sect, Immunol Lab, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, NIH, Mol Dev Sect, Immunol Lab, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI sakai, Keiko/F-5807-2013; bidere, nicolas/K-8887-2015 OI bidere, nicolas/0000-0001-9177-0008 FU Intramural NIH HHS NR 29 TC 58 Z9 62 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 22 PY 2006 VL 16 IS 16 BP 1666 EP 1671 DI 10.1016/j.cub.2006.06.062 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 079DJ UT WOS:000240155400032 PM 16920630 ER PT J AU Colton, CA Vitek, MP Wink, DA Xu, Q Cantillana, V Previti, ML Van Nostrand, WE Weinberg, B Dawson, H AF Colton, C. A. Vitek, M. P. Wink, D. A. Xu, Q. Cantillana, V. Previti, M. L. Van Nostrand, W. E. Weinberg, B. Dawson, H. TI NO synthase 2 (NOS2) deletion promotes multiple pathologies in a mouse model of Alzheimer's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid; chronic neurodegeneration; inducible nitric oxide synthase; nitric oxide; tau ID NITRIC-OXIDE SYNTHASE; TG2576 TRANSGENIC MICE; AMYLOID-BETA PROTEIN; NEUROFIBRILLARY TANGLES; TAU-PROTEIN; A-BETA; ABERRANT EXPRESSION; CASPASE-CLEAVAGE; SENILE PLAQUES; BRAIN-INJURY AB Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between amyloid and tau aggregates is of intense interest, but mouse models have yet to reveal a direct interrelationship. We now show that NO may be a key factor that connects amyloid and tau pathologies. Genetic removal of NO synthase 2 in mice expressing mutated amyloid precursor protein results in pathological hyperphosphorylation of mouse tau, its redistribution to the somatodendritic compartment in cortical and hippocampal neurons, and aggregate formation. Lack of NO synthase 2 in the amyloid precursor protein Swedish mutant mouse increased insoluble beta-amyloid peptide levels, neuronal degeneration, caspase-3 activation, and tau cleavage, suggesting that NO acts at a junction point between beta-amyloid peptides, caspase activation, and tau aggregation. C1 Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. RP Colton, CA (reprint author), Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. EM glia01@aol.com FU NIA NIH HHS [AG19740, AG19780, R01 AG019740, R01 AG019780] NR 59 TC 80 Z9 85 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 AUG 22 PY 2006 VL 103 IS 34 BP 12867 EP 12872 DI 10.1073/pnas.0601075103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077NI UT WOS:000240035900041 PM 16908860 ER PT J AU Michaud, J Kohno, M Proia, RL Hla, T AF Michaud, Jason Kohno, Masataka Proia, Richard L. Hla, Timothy TI Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice SO FEBS LETTERS LA English DT Article DE sphingosine kinase; sphingolipids; inflammation; arthritis ID COLLAGEN-INDUCED ARTHRITIS; PROTEIN-KINASE-C; N-METHYL DERIVATIVES; HUMAN-NEUTROPHILS; IN-VIVO; CYTOKINE PRODUCTION; OXIDATIVE BURST; INHIBITION; RECEPTOR; SPHINGOSINE-1-PHOSPHATE AB Sphingosine-1-phosophate, generated from the phosphorylation of sphingosine by sphingosine kinase enzymes, is suggested to function as an intracellular second messenger for inflammatory mediators, including formyl peptide, C5a, and Fc. More recently, a role for sphingosine kinases during inflammation has also been proposed. Here we show that sphingosine kinase 1 knockout mice exhibit normal inflammatory cell recruitment during thioglycollate-induced peritonitis and that sphingosine kinase 1-null neutrophils respond normally to formyl peptide. In the collagen-induced arthritis model of rheumatoid arthritis, sphingosine kinase 1 knockout mice developed arthritis with normal incidence and severity. Our findings show that sphingosine kinase 1 is dispensable for inflammatory responses and support the need for more extensive studies of sphingosine kinases in inflammation. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, Farmington, CT 06030 USA. Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kyoto 6028566, Japan. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hla, T (reprint author), Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, 263 Farmington Ave, Farmington, CT 06030 USA. EM hla@nso2.uchc.edu RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 FU NHLBI NIH HHS [HL70694, HL67330] NR 31 TC 53 Z9 56 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 21 PY 2006 VL 580 IS 19 BP 4607 EP 4612 DI 10.1016/j.febslet.2006.07.035 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 077YT UT WOS:000240068400009 PM 16876794 ER PT J AU Bash, R Wang, H Anderson, C Yodh, J Hager, G Lindsay, SM Lohr, D AF Bash, R. Wang, H. Anderson, C. Yodh, J. Hager, G. Lindsay, S. M. Lohr, D. TI AFM imaging of protein movements: Histone H2A-H2B release during nucleosome remodeling SO FEBS LETTERS LA English DT Article DE chromatin; nucleosome; remodeling; Swi-Snf; histones; SPM; AFM ID ATOMIC-FORCE MICROSCOPY; GLUCOCORTICOID-RECEPTOR; CHROMATIN; DNA; DISPLACEMENT; COMPLEXES; PROMOTER; BINDING; ARRAYS AB Being able to follow assembly/disassembly reactions of biomolecular complexes directly at the single molecule level would be very useful. Here, we use an AFM technique that can simultaneously obtain topographic images and identify the locations of a specific type of protein within those images to monitor the histone H2A component of nucleosomes acted on by human Swi-Snf, an ATP-dependent nucleosome remodeling complex. Activation of remodeling results in significant H2A release from nucleosomes, based on recognition imaging and nucleosome height changes, and changes in the recognition patterns of H2A associated directly with hSwi-Snf complexes. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. Midwestern Univ, Arizona Coll Osteopath Med, Div Basic Sci, Glendale, AZ 85308 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. RP Lindsay, SM (reprint author), Arizona State Univ, Biodesign Inst, Tempe, AZ 85287 USA. EM Stuart.Lindsay@asu.edu FU NCI NIH HHS [R01 CA085990-03] NR 20 TC 37 Z9 39 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 21 PY 2006 VL 580 IS 19 BP 4757 EP 4761 DI 10.1016/j.febslet.2006.06.101 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 077YT UT WOS:000240068400032 PM 16876789 ER PT J AU Kalueff, AV Gallagher, PS Murphy, DL AF Kalueff, Allan V. Gallagher, Pamela S. Murphy, Dennis L. TI Are serotonin transporter knockout mice 'depressed'?: hypoactivity but no anhedonia SO NEUROREPORT LA English DT Article DE anhedonia; depression; C57BL/6 genetic background; hedonic behavior; knockout mice; serotonin transporter; sucrose preference ID STRESS-INDUCED ANHEDONIA; CHRONIC MILD STRESS; MAJOR DEPRESSION; DEFICIENT MICE; 5-HTT GENE; LACKING; MODELS; PREFERENCE; SUCROSE; MOUSE AB Although the serotonin transporter is a key target for antidepressants, its exact role in depression etiology remains unclear. While serotonin transporter knockout mice are a potential model to examine this problem, their depression profile is unclear in several 'despair' tests, and may be confounded by their hypoactivity phenotype (confirmed here by marble-burying and bedding tests). To assess depression in these mice, we evaluated wild-type, heterozygous, and serotonin transporter knockout C57BL/6 male mice on a well-validated, anhedonia-based depression paradigm, the sucrose preference test. Overall, all three genotypes showed similar sucrose preference, indicating an unaltered hedonic state. These results demonstrate that depression-like behavior (unlike hypoactivity) is not a baseline phenotypic feature of serotonin transporter knockout mice, suggesting anew that these mice do not represent a genetic model of depression. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10,Room 3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. EM kalueva@mail.nih.gov FU Intramural NIH HHS NR 29 TC 40 Z9 40 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD AUG 21 PY 2006 VL 17 IS 12 BP 1347 EP 1351 DI 10.1097/01.wnr.0000230514.08962.76 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 080VW UT WOS:000240277600024 PM 16951583 ER PT J AU Scharf, O Colevas, AD AF Scharf, Orit Colevas, A. Dimitrios TI Adverse event reporting in publications compared with sponsor database for cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGRAM AB Purpose Prospectively planned collection and analysis of adverse event (AE) data are essential parts of well-conducted clinical trials. The AE data in a trial sponsor's database should be comparable with what is stipulated in the protocol and with the AE data published. We examined whether the published AE data differ from those in the sponsor's database and from the data collection requirements stated in study protocols. Methods We searched the National Cancer Institute (NCI) Clinical Data Update System (CDUS) for studies that used the Common Toxicity Criteria version 2.0 and for which a final study publication was available. We extracted from the protocols information pertaining to AE collection and reporting methods and compared it with the methods cited in the article. We also compared the AE data in the trial publication with the AE data submitted by the investigators to CDUS. Results We identified 22 studies meeting the criteria for this review. There was considerable inconsistency between AE collection and reporting methods cited in the protocols versus final publications. AE data in the article and CDUS were not identical. Twenty-seven percent of article high-grade AEs could not be matched to agent-attributable AEs in the CDUS. Twenty-eight percent of CDUS high-grade AEs could not be matched to AEs in the corresponding article. In 14 of 22 articles, the number of high-grade AEs in CDUS differed from the number in the articles by 20% or more. Conclusion Lack of consistency in and reporting of AEs are associated with NCI database and trial publication AE data discrepancy. C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. PSI Int Inc, Fairfax, VA USA. RP Colevas, AD (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Execut Plaza N Room 7131,6130 Execut Blvd, Rockville, MD 20852 USA. EM colevasd@ctep.nci.nih.gov NR 11 TC 55 Z9 58 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2006 VL 24 IS 24 BP 3933 EP 3938 DI 10.1200/JCO.2005.05.3959 PG 6 WC Oncology SC Oncology GA 077TD UT WOS:000240052300020 PM 16921045 ER PT J AU Braga-Basaria, M Dobs, AS Muller, DC Carducci, MA John, M Egan, J Basaria, S AF Braga-Basaria, Milena Dobs, Adrian S. Muller, Denis C. Carducci, Michael A. John, Majnu Egan, Josephine Basaria, Shehzad TI Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MIDDLE-AGED MEN; HORMONE-BINDING GLOBULIN; CORONARY-ARTERY-DISEASE; INSULIN-RESISTANCE; BODY-COMPOSITION; SEX-HORMONES; RISK-FACTORS; ELDERLY-MEN; TESTOSTERONE; HYPOGONADISM AB Purpose Prostate cancer (PCa) is one of the most common cancers in men. Men with recurrent or metastatic PCa are treated with androgen-deprivation therapy (ADT), resulting in profound hypogonadism. Because male hypogonadism is a risk factor for metabolic syndrome and men with PCa have high cardiovascular mortality, we evaluated the prevalence of metabolic syndrome in men undergoing long-term ADT. Patients and Methods This was a cross-sectional study. We evaluated 58 men, including 20 with PCa undergoing ADT for at least 12 months (ADT group), 18 age-matched men with nonmetastatic PCa who had received local treatment and were recently found to have an increasing prostate-specific antigen (non-ADT group), and 20 age-matched controls (control group). Men in the non-ADT and control groups were eugonadal. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Results Mean age was similar among the groups. Men on ADT had significantly higher body mass index and lower total and free testosterone levels. The prevalence of metabolic syndrome was higher in the ADT group compared with the non-ADT (P < .01) and control (P = .03) groups. Among the components of metabolic syndrome, men on ADT had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated triglycerides compared with controls (P = .02). The prevalence of hypertension and low high-density lipoprotein levels were similar. Conclusion These data suggest that metabolic syndrome was present in more than 50% of the men undergoing long-term ADT, predisposing them to higher cardiovascular risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence. We recommend prospective studies to further delineate this association. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab,Bayview Med Ctr, Baltimore, MD 21224 USA. Johns Hopkins, Kimmel Canc Ctr, Prostate Canc Res Program, Dept Oncol, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. RP Basaria, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab,Bayview Med Ctr, 4940 Eastern Ave,Ste B-114, Baltimore, MD 21224 USA. EM sbasari1@jhmi.edu FU NCRR NIH HHS [M01RR00052] NR 28 TC 285 Z9 289 U1 1 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2006 VL 24 IS 24 BP 3979 EP 3983 DI 10.1200/JCO.2006.05.9741 PG 5 WC Oncology SC Oncology GA 077TD UT WOS:000240052300027 PM 16921050 ER PT J AU Lisk, G Desai, SA AF Lisk, Godfrey Desai, Sanjay A. TI Improved perfusion conditions for patch-clamp recordings on human erythrocyte SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE patch-clamp; erythrocyte; malaria; PSAC; perfusion; electrophysiology; Plasmodium falciparum ID SURFACE ANION CHANNEL; FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; PLASMODIUM-FALCIPARUM; MALARIA PARASITES; MEMBRANE; PERMEABILITY; TRANSPORT; CURRENTS AB Various configurations of the patch-clamp method are powerful tools for examining the transport of charged solutes across biological membranes. Originally developed for the study of relatively large cells which adhere to solid surfaces under in vitro culture, these methods have been increasingly applied to small cells or organelles in suspension. Under these conditions, a number of significant technical problems may arise as a result of the smaller geometry. Here, we examined these problems using human erythrocytes infected with the malaria parasite, Plasmodium falciparum, a system where experimental differences and the technical difficulty of erythrocyte patch-clamp have hindered universal agreement on the properties of the induced ion channels. We found that patch-clamp recordings on infected erythrocytes are especially susceptible to artifacts from mechanical perturbations due to solution flow around the cell. To minimize these artifacts, we designed a new perfusion chamber whose geometry allows controlled solution flow around the fragile erythrocyte. Not only were recordings acquired in this chamber significantly less susceptible to perfusion artifacts, but the chamber permitted rapid and reversible application of known inhibitors with negligible mechanical agitation. Electrophysiological recordings then faithfully reproduced several findings made with more traditional methods. The new perfusion chamber should also be useful for patch-clamp recordings on blood cells, protoplasts, and organelles. Published by Elsevier Inc. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009 FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI000882-05] NR 30 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 18 PY 2006 VL 347 IS 1 BP 158 EP 165 DI 10.1016/j.bbrc.2006.06.058 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 065ZC UT WOS:000239198000022 PM 16806068 ER PT J AU Josephson, R Sykes, G Liu, Y Ording, C Xu, WN Zeng, XM Shin, S Loring, J Maitra, A Rao, MS Auerbach, JM AF Josephson, Richard Sykes, Gregory Liu, Ying Ording, Carol Xu, Weining Zeng, Xianmin Shin, Soojung Loring, Jeanne Maitra, Anirban Rao, Mahendra S. Auerbach, Jonathan M. TI A molecular scheme for improved characterization of human embryonic stem cell lines SO BMC BIOLOGY LA English DT Article ID NUCLEOTIDE POLYMORPHISM ARRAYS; GENE-EXPRESSION SIGNATURES; HUMAN BLASTOCYSTS; RETINOIC ACID; COPY NUMBER; IN-VITRO; DIFFERENTIATION; MICROARRAY; DERIVATION; CULTURE AB Background: Human embryonic stem cells (hESC) offer a renewable source of a wide range of cell types for use in research and cell-based therapies to treat disease. Inspection of protein markers provides important information about the current state of the cells and data for subsequent manipulations. However, hESC must be routinely analyzed at the genomic level to guard against deleterious changes during extensive propagation, expansion, and manipulation in vitro. Results: We found that short tandem repeat (STR) analysis, human leukocyte antigen (HLA) typing, single nucleotide polymorphism (SNP) genomic analysis, mitochondrial DNA sequencing, and gene expression analysis by microarray can be used to fully describe any hESC culture in terms of its identity, stability, and undifferentiated state. Conclusion: Here we describe, using molecular biology alone, a comprehensive characterization of 17 different hESC lines. The use of amplified nucleic acids means that for the first time full characterization of hESC lines can be performed with little time investment and a minimum of material. The information thus gained will facilitate comparison of lines and replication of results between laboratories. C1 ATCC, Stem Cell Ctr, Manassas, VA USA. ATCC, Dept Cell Biol, Manassas, VA USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. Buck Inst Age Res, Novato, CA USA. Burnham Inst, La Jolla, CA 92037 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Genet Med, Baltimore, MD 21218 USA. Invitrogen Corp, Carlsbad, CA USA. RP Josephson, R (reprint author), ATCC, Stem Cell Ctr, Manassas, VA USA. EM rjosephson@globalstem.com; gsykes@atcc.org; ying.liu1@invitrogen.com; ordingcj@aol.com; wxu@globalstem.com; xzeng@buckinstitute.org; soojung.shin@invitrogen.com; jloring@burnham.org; amaitra1@jhmi.edu; mahendra.rao@invitrogen.com; jauerbach@globalstem.com FU NIA NIH HHS [N01AG40002] NR 41 TC 30 Z9 31 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD AUG 18 PY 2006 VL 4 AR 28 DI 10.1186/1741-7007-4-28 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 095CV UT WOS:000241286700001 PM 16919167 ER PT J AU Ansari, R Mahdavinia, M Sadjadi, A Nouraie, M Kamangar, F Bishehsari, F Fakheri, H Semnani, S Arshi, S Zahedi, MJ Darvish-Moghadam, S Mansour-Ghanaei, F Mosavi, A Malekzadeh, R AF Ansari, Reza Mahdavinia, Mahboobeh Sadjadi, Ahreza Nouraie, Mehdi Kamangar, Farin Bishehsari, Faraz Fakheri, Hafez Semnani, Shahriar Arshi, Shahnam Zahedi, Mohammad-Javad Darvish-Moghadam, Sodeif Mansour-Ghanaei, Fariborz Mosavi, Alireza Malekzadeh, Reza TI Incidence and age distribution of colorectal cancer in Iran: Results of a population-based cancer registry SO CANCER LETTERS LA English DT Article DE colorectal cancer; incidence; Iran ID PATIENTS LESS; ADENOCARCINOMA; CARCINOMA; COLON; RECTUM AB Epidemiologic patterns of colorectal cancer (CRC) in Iran have not been studied adequately. In a recent cancer registry and active cancer surveillance, we collected data on the incidence of colorectal tumors in five provinces of Iran from 1996 to 2000. In total, 2055 were registered in this study. Age-adjusted rates of CRC in Iranian males and females were 8.2 and 7.0/100,000, respectively. Seventeen percent of the cases were younger than 40 years of age at the time of diagnosis. This proportion was similar to proportions seen in many other Middle-Eastern countries, but much higher than those seen in Western countries. A comparison of age-specific rates between Iran and the US showed similar rates in young (< 40 years) Iranians and Americans, but much lower rates in older (>= 40) Iranians. We conclude that Iran is still a country with low-risk of CRC, particularly for older individuals. The high proportions of young CRC cases seen in Iran, and probably many neighboring countries, are due to the young age-structure of these countries and relatively low rates of CRC in older individuals. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran 14114, Iran. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Mazandaran Univ Med Sci, Sari, Iran. Golestan Univ Med Sci, Gorgan, Iran. Ardabil Univ Med Sci, Ardabil, Iran. Kerman Univ Med Sci, Kerman, Iran. Gilan Univ Med Sci, Gastrointestinal & Liver Res Ctr, Rasht, Iran. Univ Tehran Med Sci, Inst Canc, Tehran 14114, Iran. RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, N Kargar Ave, Tehran 14114, Iran. EM malek@ams.ac.ir RI Semnani, Shahryar/N-2270-2016; Mansour-Ghaanei, Fariborz/P-7240-2016; OI Semnani, Shahryar/0000-0002-8768-6142; mansour-ghanaei, fariborz/0000-0002-6264-0025; Malekzadeh, Reza/0000-0003-1043-3814 NR 19 TC 63 Z9 64 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD AUG 18 PY 2006 VL 240 IS 1 BP 143 EP 147 DI 10.1016/j.canlet.2005.09.004 PG 5 WC Oncology SC Oncology GA 077SX UT WOS:000240051600017 PM 16288832 ER PT J AU Seubert, JM Sinal, CJ Graves, J DeGraff, LM Bradbury, JA Lee, CR Goralski, K Carey, MA Luria, A Newman, JW Hammock, BD Falck, JR Roberts, H Rockman, HA Murphy, E Zeldin, DC AF Seubert, John M. Sinal, Christopher J. Graves, Joan DeGraff, Laura M. Bradbury, J. Alyce Lee, Craig R. Goralski, Kerry Carey, Michelle A. Luria, Ayala Newman, John W. Hammock, Bruce D. Falck, John R. Roberts, Holly Rockman, Howard A. Murphy, Elizabeth Zeldin, Darryl C. TI Role of soluble epoxide hydrolase in postischemic recovery of heart contractile function SO CIRCULATION RESEARCH LA English DT Article DE arachidonic acid; cytochrome P450; eicosanoid; ischemia/reperfusion ID EPOXYEICOSATRIENOIC ACID METABOLISM; PERMEABILITY TRANSITION PORE; CA2+-ACTIVATED K+ CHANNELS; RAT VENTRICULAR MYOCYTES; ARACHIDONIC-ACID; CORONARY-ARTERIES; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; CYTOCHROME-P450; INHIBITION AB Cytochrome P450 epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) which are converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (Ephx2, sEH). To examine the functional role of sEH in the heart, mice with targeted disruption of the Ephx2 gene were studied. Hearts from sEH null mice have undetectable levels of sEH mRNA and protein and cannot convert EETs to DHETs. sEH null mice have normal heart anatomy and basal contractile function, but have higher fatty acid epoxide: diol ratios in plasma and cardiomyocyte cell culture media compared with wild type (WT). sEH null hearts have improved recovery of left ventricular developed pressure (LVDP) and less infarction compared with WT hearts after 20 minutes ischemia. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid ( 10 to 100 nmol/L) before ischemia abolishes this cardioprotective phenotype. Inhibitor studies demonstrate that perfusion with phosphatidylinositol-3 kinase (PI3K) inhibitors wortmannin (200 nmol/L) or LY294002 (5 mu mol/ L), the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide (1 mu mol/ L), the mitochondrial KATP (mitoKATP) inhibitor 5-hydroxydecanoate (100 to 200 mu mol/L), or the Ca2+-sensitive K+ channel (KCa) inhibitor paxilline (10 mu mol/ L) abolishes the cardioprotection in sEH null hearts. Consistent with increased activation of the PI3K cascade, sEH null mice exhibit increased cardiac expression of glycogen synthase kinase-3 beta(GSK-3 beta) phospho-protein after ischemia. Together, these data suggest that targeted disruption of sEH increases the availability of cardioprotective EETs that work by activating PI3K signaling pathways and K+ channels. C1 Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB, Canada. Dalhousie Univ, Dept Pharmacol, Halifax, NS, Canada. Univ Calif Davis, Dept Entomol & Canc Res Ctr, Davis, CA 95616 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX USA. Duke Univ, Ctr Med, Dept Med, Durham, NC USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Falck, John/0000-0002-9219-7845; Lee, Craig/0000-0003-3595-5301 FU Intramural NIH HHS [Z01 ES025034-13]; NIEHS NIH HHS [F32 ES012856-01, ES012856, ES04699, F32 ES012856, F32 ES012856-02, F32 ES012856-03, P42 ES004699] NR 42 TC 118 Z9 123 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 18 PY 2006 VL 99 IS 4 BP 442 EP 450 DI 10.1161/01.RES.0000237390.92932.37 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 074RL UT WOS:000239829400018 PM 16857962 ER EF