FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Dunson, DB AF Dunson, DB TI Special issue of statistical methods in medical research on reproductive studies SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Editorial Material C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niebs.nib.gov NR 0 TC 1 Z9 1 U1 1 U2 2 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD APR PY 2006 VL 15 IS 2 BP 91 EP 92 DI 10.1191/0962280206sm432ed PG 2 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 030YD UT WOS:000236670400001 ER PT J AU Louis, GB Dukic, V Heagerty, PJ Louis, TA Lynch, CD Ryan, LM Schisterman, EF Trumble, A AF Louis, GB Dukic, V Heagerty, PJ Louis, TA Lynch, CD Ryan, LM Schisterman, EF Trumble, A CA Pregnancy Modeling Working Grp TI Analysis of repeated pregnancy outcomes SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID LOW-BIRTH-WEIGHT; CORRELATED RESPONSE DATA; LONGITUDINAL DATA; GESTATIONAL-AGE; CAUTIONARY NOTE; MODELS; RISK; RECURRENCE; INFERENCE; DEFECTS AB Women tend to repeat reproductive outcomes, with past history of an adverse outcome being associated with an approximate two-fold increase in subsequent risk. These observations support the need for statistical designs and analyses that address this clustering. Failure to do so may mask effects, result in inaccurate variance estimators, produce biased or inefficient estimates of exposure effects. We review and evaluate basic analytic approaches for analysing reproductive outcomes, including ignoring reproductive history, treating it as a covariate or avoiding the clustering problem by analysing only one pregnancy per woman, and contrast these to more modern approaches such as generalized estimating equations with robust standard errors and mixed models with various correlation structures. We illustrate the issues by analysing a sample from the Collaborative Perinatal Project dataset, demonstrating how the statistical model impacts summary statistics and inferences when assessing etiologic determinants of birth weight. C1 NICHHD, Germaine Buck Louis Div Epidemiol Stat & Prevent, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Louis, GB (reprint author), NICHHD, Germaine Buck Louis Div Epidemiol Stat & Prevent, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM louisg@mail.nih.gov RI Ryan, Louise/A-4562-2009; OI Ryan, Louise/0000-0001-5957-2490; Dukic, Vanja/0000-0002-0348-0834; Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural NIH HHS NR 37 TC 42 Z9 43 U1 0 U2 6 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD APR PY 2006 VL 15 IS 2 BP 103 EP 126 DI 10.1191/0962270206sm434oa PG 24 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 030YD UT WOS:000236670400003 PM 16615652 ER PT J AU Bryja, V Bonilla, S Cajanek, L Parish, CL Schwartz, CM Luo, YQ Rao, MS Arenas, E AF Bryja, Vitezslav Bonilla, Sonia Cajanek, Lukas Parish, Clare L. Schwartz, Catherine M. Luo, Yongquan Rao, Mahendra S. Arenas, Ernest TI An efficient method for the derivation of mouse embryonic stem cells SO STEM CELLS LA English DT Article DE mouse embryonic stem cells; derivation from blastocyst; efficient protocol; serum-free media ID IMPROVED GENERATION; HUMAN BLASTOCYSTS; LINES; CULTURE; MICE AB Mouse embryonic stem cells (mESCs) represent a unique tool for many researchers; however, the process of ESC derivation is often very inefficient and requires high specialization, training, and expertise. To circumvent these limitations, we aimed to develop a simple and efficient protocol based on the use of commercially available products. Here, we present an optimized protocol that we successfully applied to derive ESCs from several knockout mouse strains (Wnt-1, Wnt-5a, Lrp6, and parkin) with 50%-75% efficiency. The methodology is based on the use of mouse embryonic fibroblast feeders, knockout serum replacement (SR), and minimal handling of the blastocyst. In this protocol, all centrifugation steps (as well as the use of trypsin inhibitor) were avoided and replaced by an ESC medium containing fetal calf serum (FCS) after the trypsinizations. We define the potential advantages and disadvantages of using SR and FCS in individual steps of the protocol. We also characterize the ESCs for the expression of ESC markers by immunohistochemistry, Western blot, and a stem cell focused microarray. In summary, we provide a simplified and improved protocol to derive mESCs that can be useful for laboratories aiming to isolate transgenic mESCs for the first time. C1 Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Lab, S-17177 Stockholm, Sweden. NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Lab Neurosci,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Arenas, E (reprint author), Karolinska Inst, Dept Med Biochem & Biophys, Mol Neurobiol Lab, S-17177 Stockholm, Sweden. EM ernest.arenas@ki.se RI Parish, Clare/A-3380-2014; Bryja, Vit?zslav/H-1925-2014; OI Bryja, Vit?zslav/0000-0002-9136-5085; Cajanek, Lukas/0000-0003-2914-8589; Arenas, Ernest/0000-0003-0197-6577 NR 22 TC 51 Z9 66 U1 0 U2 8 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 APR PY 2006 VL 24 IS 4 BP 844 EP 849 DI 10.1634/stemcells.2005-0444 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WY UT WOS:000240636300007 PM 16339993 ER PT J AU Luo, YQ Schwartz, C Shin, S Zeng, XM Chen, N Wang, Y Yu, X Rao, MS AF Luo, Yongquan Schwartz, Catherine Shin, Soojung Zeng, Xianmin Chen, Nong Wang, Yue Yu, Xiang Rao, Mahendra S. TI A focused microarray to assess dopaminergic and glial cell differentiation from fetal tissue or embryonic stem cells SO STEM CELLS LA English DT Article DE human embryonic stem cells; differentiation; oligodendrocytes; astrocytes; dopamienrgic neurons ID NEUROLOGICAL DISORDERS; TARGETED DISRUPTION; ADULT NEUROGENESIS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; NEURONS; MIDBRAIN; PROLIFERATION; NURR1; FATE AB We designed oligonucleotide gene-specific probes to develop a focused array that can be used to discriminate between neural phenotypes, identify biomarkers, and provide an overview of the process of dopaminergic neuron and glial differentiation. We have arrayed approximately 100 genes expressed in dopaminergic neurons, oligodendrocytes, and astrocytes, an additional 200 known cytokines, chemokines, and their respective receptors, as well as markers for pluripotent and progenitor cells. The gene-specific 60-mer 3' biased oligonucleotides for these 281 genes were arrayed in a 25 x 12 format based on function. Using human adult brain substantia nigra, human embryonic stem cells (ESCs), and the differentiated progeny of pluripotent cells, we showed that this array was capable of distinguishing dopaminergic neurons, glial cells, and pluripotent cells by their gene expression profiles in a concentration-dependent manner. Using linear correlation coefficients of input RNA with output intensity, we identified a list of genes that can serve as reporting genes for detecting dopaminergic neurons, glial cells, and contaminating ESCs and progenitors. Finally, we monitored NTera2 differentiation toward dopaminergic neurons and have shown the ability of this array to distinguish stages of differentiation and provide important clues to factors regulating differentiation, the degree of contaminating populations, and stage of cell maturity. We suggest that this focused array will serve as a useful complement to other large-scale arrays in routine assessment of cell properties prior to their therapeutic use. C1 Invitrogen Corp, Carlsbad, CA 92008 USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. SuperArray Biosci Corp, Frederick, MD USA. Buck Inst Age Res, Novato, CA USA. Karolinska Inst, Retzius Lab, Lab Mol Neurobiol Med Biochem & Biophys, Stockholm, Sweden. NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Neurosci Lab,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Rao, MS (reprint author), Invitrogen Corp, 1600 Faraday Rd, Carlsbad, CA 92008 USA. EM mahendra.rao@invitrogen.com FU Intramural NIH HHS NR 25 TC 15 Z9 16 U1 0 U2 0 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 APR PY 2006 VL 24 IS 4 BP 865 EP 875 DI 10.1634/stemcells.2005-0392 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WY UT WOS:000240636300010 PM 16357341 ER PT J AU Aiba, K Sharov, AA Carter, MG Foroni, C Vescovi, AL Ko, MSH AF Aiba, Kazuhiro Sharov, Alexei A. Carter, Mark G. Foroni, Chiara Vescovi, Angelo L. Ko, Minoru S. H. TI Defining a developmental path to neural fate by global expression profiling of mouse embryonic stem cells and adult neural stem/progenitor cells SO STEM CELLS LA English DT Article DE embryonic stem cells; principal component analysis; neural commitment; neural differentiation; microarray ID GENE-EXPRESSION; MICROARRAY DATA; NEURONAL DIFFERENTIATION; NERVOUS-SYSTEM; IN-VITRO; TOOL; PLURIPOTENCY; GENERATION; ONTOLOGY; GENMAPP AB To understand global features of gene expression changes during in vitro neural differentiation, we carried out the microarray analysis of embryonic stem cells (ESCs), embryonal carcinoma cells, and adult neural stem/progenitor (NS) cells. Expression profiling of ESCs during differentiation in monolayer culture revealed three distinct phases: undifferentiated ESCs, primitive ectoderm-like cells, and neural progenitor cells. Principal component (PC) analysis revealed that these cells were aligned on PC1 over the course of 6 days. This PC1 represents approximately 4,000 genes, the expression of which increased with neural commitment/differentiation. Furthermore, NS cells derived from adult brain and their differentiated cells were positioned along this PC axis further away from undifferentiated ESCs than embryonic stem-derived neural progenitors. We suggest that this PC1 defines a path to neural fate, providing a scale for the degree of commitment/differentiation. C1 NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. Osped San Raffaele, Inst Stem Cell Res, Milan, Italy. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS NR 36 TC 49 Z9 50 U1 0 U2 2 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 APR PY 2006 VL 24 IS 4 BP 889 EP 895 DI 10.1634/stemcells.2005-0332 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WY UT WOS:000240636300012 PM 16357342 ER PT J AU Miura, M Miura, Y Padilla-Nash, HM Molinolo, AA Fu, BJ Patel, V Seo, BM Sonoyama, W Zheng, JJ Baker, CC Chen, WJ Ried, T Shi, ST AF Miura, Masako Miura, Yasuo Padilla-Nash, Hesed M. Molinolo, Alfredo A. Fu, Baojin Patel, Vyomesh Seo, Byoung-Moo Sonoyama, Wataru Zheng, Jenny J. Baker, Carl C. Chen, Wanjun Ried, Thomas Shi, Songtao TI Accumulated chromosomal instability in murine bone marrow mesenchymal stem cells leads to malignant transformation SO STEM CELLS LA English DT Article DE bone marrow-derived mesenchymal stem cell; malignant transformation chromosomal instability; fibrosarcoma ID ACUTE MYELOID-LEUKEMIA; TELOMERASE EXPRESSION; STROMAL CELLS; IN-VIVO; CANCER; IDENTIFICATION; MOUSE; DIFFERENTIATION; TRANSPLANTATION; SENESCENCE AB Despite recent emerging evidence suggesting that cancer stem cells subsist in a variety of tumors, it is not yet fully elucidated whether postnatal stem cells are directly involved in tumorigenesis. We used murine bone marrow-derived mesenchymal stem cells (BMMSCs) as a model to test a hypothesis that tumorigenesis may originate from spontaneous mutation of stem cells. In this study, we demonstrated that murine BMMSCs, after numerous passages, obtained unlimited population doublings and proceeded to a malignant transformation state, resulting in fibrosarcoma formation in vivo. Transformed BMMSCs colonized to multiple organs when delivered systemically through the tail vein. Fibrosarcoma cells formed by transformed BMMSCs contained cancer progenitors, which were capable of generating colony clusters in vitro and fibrosarcoma in vivo by the second administration. The mechanism by which BMMSCs transformed to malignant cells was associated with accumulated chromosomal abnormalities, gradual elevation in telomerase activity, and increased c-myc expression. Moreover, BMMSCs and their transformed counterpart, fibrosarcoma-forming cells, demonstrated different sensitivity to anti-cancer drugs. BMMSCs/fibrosarcoma transformation system may provide an ideal system to elucidate the mechanism of how stem cells become cancer cells and to screen anti-sarcoma drugs. C1 Natl Inst Dent & Craniofacial Res, Dent Biol Unit, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Food & Drug Adm, Rockville, MD 20857 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD USA. RP Shi, ST (reprint author), Natl Inst Dent & Craniofacial Res, Dent Biol Unit, NIH, Bldg 30,Room 131,30 Convent Dr MSC4320, Bethesda, MD 20892 USA. EM sshi@mail.nih.gov FU Intramural NIH HHS NR 30 TC 334 Z9 367 U1 1 U2 11 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 APR PY 2006 VL 24 IS 4 BP 1095 EP 1103 DI 10.1634/stemcells.2005-0403 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 085WY UT WOS:000240636300032 PM 16282438 ER PT J AU Tibbitts, D Rao, RR Shin, S West, FD Stice, SL AF Tibbitts, D Rao, RR Shin, S West, FD Stice, SL TI Uniform adherent neural progenitor populations from rhesus embryonic stem cells SO STEM CELLS AND DEVELOPMENT LA English DT Article ID GENE-EXPRESSION; IN-VITRO; EXTRACELLULAR-MATRIX; MOLECULAR SIGNATURE; DIFFERENTIATION; MOUSE; CULTURE; TROPHOBLAST; PRECURSORS; RECEPTORS AB Rhesus and human embryonic stem cells (ESCs) are similar, making rhesus ESCs an appropriate preclinical allograft model for refining stem cell therapies. Use of rhesus ESC-derived neural progenitors (NPs) in preclinical applications will be enhanced if the neural derivation process is scalable and free from contaminating ESCs or nonneural cells. In this study, we have quantified temporal gene expression changes of rhesus ESC differentiated to uniform NPs using simple feeder-free adherent cultures. NPs exhibited a significant up-regulation of neural-specific genes and a down-regulation of pluripotency genes. Additionally, expression of Hu, MAP2, and Tuj1, shows that NPs can form post-mitotic neurons. This study represents a simple and scalable means of producing adherent primate NPs for preclinical testing of neural cell-based therapy. C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. Virginia Commonwealth Univ, Dept Chem & Life Sci Engn, Richmond, VA 23284 USA. NIA, Stem Cell Biol Sect, Neurosci Lab, Baltimore, MD 21224 USA. Univ Georgia, Regenerat Biosci Ctr, Athens, GA 30602 USA. RP Stice, SL (reprint author), Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. EM sstice@uga.edu FU NINDS NIH HHS [NS44208-2] NR 45 TC 5 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD APR PY 2006 VL 15 IS 2 BP 200 EP 208 DI 10.1089/scd.2006.15.200 PG 9 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 040YG UT WOS:000237416700006 PM 16646666 ER PT J AU Cai, JL Shin, S Wright, L Liu, Y Zhou, DX Xue, HP Khrebtukova, I Mattson, MP Svendsen, CN Rao, MS AF Cai, JL Shin, S Wright, L Liu, Y Zhou, DX Xue, HP Khrebtukova, I Mattson, MP Svendsen, CN Rao, MS TI Massively parallel signature sequencing profiling of fetal human neural precursor cells SO STEM CELLS AND DEVELOPMENT LA English DT Article ID GENE-EXPRESSION; STEM-CELLS; PROGENITOR CELLS AB We have examined gene expression in multipotent neural precursor cells (NPCs) derived from human fetal (f) brain tissue and compared its expression profiles with embryonic stem (ESC) cells, embryoid body cell (EBC), and astrocyte precursors using the technique of massively parallel signature sequencing (MPSS). Gene expression profiles show that fNPCs express core neural stem cells markers and share expression profiles with astrocyte precursor cells (APCs) rather than ESC or EBC. Gene expression analysis shows that fNPCs differ from other adult stem and progenitor cells in their marker expression and activation of specific functional networks such as the transforming growth factor beta (TGF beta) and Notch signaling pathways. In addition, our results allow us to identify novel genes expressed in fNPCs and provide a detailed profile of fNPCs. C1 NIA, Stem Cell Biol Unit, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA. Invitrogen Corp, Corp Res Labs, Carlsbad, CA 92008 USA. Johns Hopkins Sch Med, Baltimore, MD 21287 USA. Solexa Inc, Hayward, CA 94545 USA. RP Shin, S (reprint author), NIA, Stem Cell Biol Unit, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM shinso@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 18 TC 14 Z9 15 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD APR PY 2006 VL 15 IS 2 BP 232 EP 244 DI 10.1089/scd.2006.15.232 PG 13 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 040YG UT WOS:000237416700009 PM 16646669 ER PT J AU Kruit, MC Launer, LJ Ferrari, MD van Buchem, MA AF Kruit, MC Launer, LJ Ferrari, MD van Buchem, MA TI Brain stem and cerebellar hyperintense lesions in migraine SO STROKE LA English DT Article DE cerebellum; cerebral ischemia; cerebrovascular disorders; magnetic resonance imaging; migraine; Pons ID PREVALENCE AB Background and Purpose - Migraineurs are at increased risk of cerebellar infarcts and supratentorial white matter lesions. The prevalence, frequency, and distribution of infratentorial hyperintense lesions in migraine are unknown. Methods - Migraineurs with aura ( n = 161), without aura ( n = 134), and controls ( n = 140) from a population-based sample of adults ( 30 to 60 years of age) were evaluated with MRI. Results - Infratentorial hyperintensities were identified in 13 of 295 (4.4%) migraineurs and in 1 of 140 (0.7%) controls ( P = 0.04). Twelve cases had hyperintensities, mostly bilaterally, in the dorsal basis pontis. Those with infratentorial hyperintensities also had supratentorial white matter lesions more often. Conclusion - We found an increased prevalence of infratentorial ( mostly pontine) hyperintensities in migraineurs from the general population. This extends the knowledge about vulnerable brain regions and type of lesions in migraine brains. A hemodynamic ischemic pathogenesis is likely, but further research is needed. C1 Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Neurol, NL-2300 RC Leiden, Netherlands. Natl Inst Publ Hlth & Environm, Dept Chron Dis & Environm Epidemiol, NL-3720 BA Bilthoven, Netherlands. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Kruit, MC (reprint author), Leiden Univ, Med Ctr, Dept Radiol, POB 9600, NL-2300 RC Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X FU Intramural NIH HHS NR 13 TC 89 Z9 93 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2006 VL 37 IS 4 BP 1109 EP 1112 DI 10.1161/01.STR.0000206446.26702.e9 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 025UJ UT WOS:000236292100040 PM 16497982 ER PT J AU Batra, VK Beard, WA Shock, DD Krahn, JM Pedersen, LC Wilson, SH AF Batra, VK Beard, WA Shock, DD Krahn, JM Pedersen, LC Wilson, SH TI Magnesium-induced assembly of a complete DNA polymerase catalytic complex SO STRUCTURE LA English DT Article ID INDUCED-FIT MECHANISM; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; STRUCTURAL BASIS; REVERSE-TRANSCRIPTASE; PROTEIN STRUCTURES; TERNARY COMPLEXES; BETA; FIDELITY; TEMPLATE AB The molecular details of the nucleotidyl transferase reaction have remained speculative, as strategies to trap catalytic intermediates for structure determination utilize substrates lacking the primer terminus 3'-OH and catalytic Mg2+, resulting in an incomplete and distorted active site geometry. Since the geometric arrangement of these essential atoms will impact chemistry, structural insight into fidelity strategies has been hampered. Here, we present a crystal structure of a precatalytic complex of a DNA polymerase with bound substrates that include the primer 3'-OH and catalytic Mg2+. This catalytic intermediate was trapped with a northydrolyzable deoxynucleotide analog. Comparison with two new structures of DNA polymerase beta-lacking the 3'-OH or catalytic Mg2+ is described. These structures provide direct evidence that both atoms are required to achieve a proper geometry necessary for an in-line nucleophilic attack of L3' on the alpha P of the incoming nucleotide. C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999]; NCI NIH HHS [1U19CA105010, U19 CA105010] NR 46 TC 155 Z9 155 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD APR PY 2006 VL 14 IS 4 BP 757 EP 766 DI 10.1016/j.str.2006.01.011 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 034KP UT WOS:000236928200018 PM 16615916 ER PT J AU Seneca, N Finnema, SJ Farde, L Gulyas, B Wikstrom, HV Halldin, C Innis, RB AF Seneca, N Finnema, SJ Farde, L Gulyas, B Wikstrom, HV Halldin, C Innis, RB TI Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain: A comparison of the agonist radioligand [(11C)]MNPA and antagonist [C-11]raclopride SO SYNAPSE LA English DT Article DE dopaminergic agonist; positron emission tomography; central nervous system stimulant; D-2 receptor; [C-11]MNPA ID POSITRON-EMISSION-TOMOGRAPHY; C-11 RACLOPRIDE BINDING; HIGH-AFFINITY STATES; BASE-LINE OCCUPANCY; IN-VIVO; STRIATAL DOPAMINE; ENDOGENOUS DOPAMINE; SYNAPTIC DOPAMINE; PARKINSONS-DISEASE; INVIVO BINDING AB PET measurements of stimulant-induced dopamine (DA) release are typically performed with antagonist radioligands that bind to both the high- and low-affinity state of the receptor. In contrast, an agonist radioligand binds preferentially to the high-affinity state and is expected to have greater sensitivity to DA, which is the endogenous agonist. [C-11]MNPA, (R)-2-CH3O-N-n-propylnorapomorphine (MNPA), is a D-2 agonist radioligand with subnanomolar affinity to the D-2 receptor. The aim of the present study is to assess and compare the sensitivity of the agonist radioligand [C-11]MNPA and antagonist radioligand [C-11]raclopride to synaptic DA levels. Four cynomolgus monkeys were examined with [C-11]MNPA and [C-11]raclopride (16 PET measurements with each tracer) at baseline and after pretreatment with various doses of amphetamine. The effect of amphetamine was calculated by the change in binding potential (BP) analyzed with the multilinear reference tissue model (MRTM2). Amphetamine caused a reduction in [C-11]MNPA BP of 4% at 0.1, 23% at 0.2, 25% at 0.5, and 46% at 1.0 mg/kg. [C-11]Raclopride BP was reduced to a lesser extent by 2% at 0.1, 16% at 0.2, 15% at 0.5, and 23% at 1.0 mg/kg. The data were used to estimate the in vivo percentage of high-affinity state receptors to be similar to 60%. These results demonstrate that [C-11]MNPA is more sensitive than [C-11]raclopride to displacement by endogenous DA, and that it may provide additional information about the functional state of the D-2 receptor in illnesses such as schizophrenia and Parkinson's disease. C1 Karolinska Hosp, Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, S-17176 Stockholm, Sweden. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Univ Groningen, Ctr Pharm, Dept Med Chem, NL-9713 AW Groningen, Netherlands. RP Seneca, N (reprint author), Karolinska Hosp, Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, S-17176 Stockholm, Sweden. EM Nick.Seneca@cns.ki.se RI Gulyas, Balazs/F-9508-2015 FU Intramural NIH HHS NR 59 TC 74 Z9 74 U1 3 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2006 VL 59 IS 5 BP 260 EP 269 DI 10.1002/syn.20238 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 013TJ UT WOS:000235432100002 PM 16416444 ER PT J AU Halladay, AK Wagner, GC Sekowski, A Rothman, RB Baumann, MH Fisher, H AF Halladay, AK Wagner, GC Sekowski, A Rothman, RB Baumann, MH Fisher, H TI Alterations in alcohol consumption, withdrawal seizures, and monoamine transmission in rats treated with phentermine and 5-hydroxy-L-tryptophan SO SYNAPSE LA English DT Article DE dopamine; serotonin; alcohol consumption; alcohol withdrawal; animal model; neurochemistry; microdialysis ID SEROTONIN-RELEASING AGENTS; ETHANOL WITHDRAWAL; DECARBOXYLASE INHIBITOR; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; NONPREFERRING RATS; PREFERRING RATS; DEPENDENT RATS; BRAIN; MICRODIALYSIS AB We have previously shown that coadministration of the dopamine (DA) agonist phentermine plus the serotonergic agonist fenfluramine suppresses alcohol intake and withdrawal seizures in rats. In the present study, phentermine and the serotonin (5-HT) precursor, 5-hydrOXY-L-tryptophan (5-HTP), were administered alone, or in combination, to rats fed on a 6% alcohol-containing diet or an isocaloric control diet. Following a 9-h withdrawal period from the alcohol-containing diet, phentermine enhanced the effects of 5-HTP on both reduction of alcohol withdrawal seizures as well as changes in striatal serotonin. Food intake was monitored for 24 h after drug treatment, and neurochemical measures were examined at various time points. Phentermine alone reduced food intake in all diet conditions, but this anorectic effect was followed by hyperphagia in control rats. Phentermine plus 5-HTP reduced the consumption of the alcohol-containing diet, while its effects on consumption of control diets were mixed. In vivo microdialysis in rat nucleus accumbens revealed that phentermine increased extracellular DA, whereas 5-HTP caused marked elevations in extracellular 5-HT. Coadministration of phentermine and 5-HTP evoked simultaneous elevations in extracellular DA and 5-HT that mirrored the effects of each drug alone. Collectively, these findings show that coadministered phentermine plus 5-HTP is effective in reducing alcohol intake and suppressing alcohol withdrawal seizures. These therapeutic actions may be related to elevations in synaptic DA and 5-HT in critical brain regions. C1 Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08901 USA. Rutgers State Univ, Dept Pharmacol & Toxicol, New Brunswick, NJ 08901 USA. Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08901 USA. NIDA, Clin Psychopharmacol Sect, IRP, DHHS,NIH, Baltimore, MD 21224 USA. RP Fisher, H (reprint author), Rutgers State Univ, Dept Nutr Sci, Thompson Hall, New Brunswick, NJ 08901 USA. EM fisher@aesop.rutgers.edu FU Intramural NIH HHS; NIEHS NIH HHS [ES11259/EPA82939101, ES05022, ES11729]; NINDS NIH HHS [NS43981] NR 54 TC 10 Z9 10 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2006 VL 59 IS 5 BP 277 EP 289 DI 10.1002/syn.20239 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 013TJ UT WOS:000235432100004 PM 16416445 ER PT J AU Hoffmann, J Alt, A Lin, JH Lochnit, G Schubert, U Schleicher, E Chavakis, T Brownlee, M Van der Woude, FJ Preissner, KT Hammes, HP AF Hoffmann, J Alt, A Lin, JH Lochnit, G Schubert, U Schleicher, E Chavakis, T Brownlee, M Van der Woude, FJ Preissner, KT Hammes, HP TI Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE experimental diabetic retinopathy; pericytes; endothelial survivaI; VEGF; tenilsetam ID ENDOTHELIAL GROWTH-FACTOR; PROTEIN CROSS-LINKING; RETINAL METABOLISM; IN-VITRO; AMINOGUANIDINE; CELLS; COMPLICATIONS; ANGIOGENESIS; INHIBITION; SYSTEM AB Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species leads to the activation of different biochemical pathways involved in endothelial damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is a dicarbonyl scavenger in the millimolar range and a transition metal ion chelator in the micromolar range. We tested its effect on experimental diabetic retinopathy, and on endothelial cell characteristics in vitro. Streptozotocin diabetic male Wistar rats (60 mg/ kg BW) received 50 mg/kg BW tenilsetam (D-T) for 36 weeks, or no treatment (D). The impact of tenilsetam (0-30 mM) on endothelial proliferation, apoptosis, sprouting, cytokine-induced leucocyte-endothelial interaction, and VEGF expression was tested in vitro. Tenilsetam did not affect glycemic control or body weight in diabetic animals. The 3.7 fold increase in acellular capillaries in diabetic rats [p < 0.001 vs. non-diabetic controls (N)] was reduced by 70% (p < 0.001) through treatment, but pericyte loss (D vs. N -33%; p < 0.001) remained unaffected. In vitro, tenilsetam inhibited endothelial proliferation at lower doses,while inducing apoptosis at high doses. Leucocyte adhesion was only inhibited at high doses. Sprouting angiogenesis of bovine retinal endothelial cells was promoted at lower doses (<= 10 mM). At micromolar concentrations, endothelial VEGF expression was upregulated by 100%. Long-term treatment with the AGE-inhibitor and iron-chelating compound tenilsetam inhibits the formation of acellular capillaries without correcting pericyte loss. The compound has dose-dependent effects on endothelial cell function. These data suggest that, independent of known properties, tenilsetam shows important rescue functions on endothelial cells which could be useful for the treatment of early diabetic retinopathy. C1 Univ Heidelberg, Fac Clin Med, Dept Med 5, D-68167 Mannheim, Germany. Univ Giessen, Dept Med 3, Giessen, Germany. Univ Giessen, Inst Biochem, Giessen, Germany. Univ Tubingen, Dept Internal Med 4, D-72074 Tubingen, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Hammes, HP (reprint author), Univ Heidelberg, Univ Hosp, Fac Clin Med, Dept Med 5, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM hans-peter.hammes@med5.ma.uni-heidelberg.de NR 45 TC 8 Z9 8 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2006 VL 95 IS 4 BP 689 EP 695 DI 10.1160/TH05-11-0725 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 035TW UT WOS:000237025600015 PM 16601840 ER PT J AU Peraza, MA Burdick, AD Marin, HE Gonzalez, FJ Peters, JM AF Peraza, MA Burdick, AD Marin, HE Gonzalez, FJ Peters, JM TI The toxicology of ligands for peroxisome proliferator-activated receptors (PPAR) SO TOXICOLOGICAL SCIENCES LA English DT Review DE peroxisome proliferator-activated receptors (PPAR); toxicity; carcinogenesis; receptor-mediated toxicology ID COLON-CANCER CELLS; HEPATIC STELLATE CELLS; ACUTE-RENAL-FAILURE; HUMAN BREAST-CANCER; NF-KAPPA-B; LOW-DENSITY-LIPOPROTEIN; HUMAN PANCREATIC-CANCER; LUNG-CARCINOMA-CELLS; RETINOID-X-RECEPTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS AB Peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors that modulate target gene expression in response to endogenous and exogenous ligands. Ligands for the PPARs have been widely developed for the treatment of various diseases including dyslipidemias and diabetes. While targeting selective receptor activation is an established therapeutic approach for the treatment of various diseases, a variety of toxicities are known to occur in response to ligand administration. Whether PPAR ligands produce toxicity via a receptor-dependent and/or off-target-mediated mechanism(s) is not always known. Extrapolation of data derived from animal models and/or in vitro models, to humans, is also questionable. The different toxicities and mechanisms associated with administration of ligands for the three PPARs will be discussed, and important data gaps that could increase our current understanding of how PPAR ligands lead to toxicity will be highlighted. C1 Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU NCI NIH HHS [CA89607, CA97999] NR 339 TC 152 Z9 161 U1 3 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2006 VL 90 IS 2 BP 269 EP 295 DI 10.1093/toxsci/kfj062 PG 27 WC Toxicology SC Toxicology GA 023DQ UT WOS:000236106000001 PM 16322072 ER PT J AU Jackson, MA Lea, I Rashid, A Peddada, SD Dunnick, JK AF Jackson, MA Lea, I Rashid, A Peddada, SD Dunnick, JK TI Genetic alterations in cancer knowledge system: Analysis of gene mutations in mouse and human liver and lung tumors SO TOXICOLOGICAL SCIENCES LA English DT Review DE genetic alteration; mutation; lung tumor; liver tumor; environmental exposure; database ID K-RAS MUTATIONS; HUMAN HEPATOCELLULAR-CARCINOMA; BETA-CATENIN MUTATIONS; CONFORMATION POLYMORPHISM ANALYSIS; DNA ADDUCT FORMATION; FEMALE B6C3F1 MICE; HONG-KONG CHINESE; STRAIN A/J MICE; P53 GENE; HA-RAS AB Mutational incidence and spectra for genes examined in both human and mouse lung and liver tumors were analyzed using the National Institute of Environmental Health Sciences (NIEHS) Genetic Alterations in Cancer (GAC) knowledge system. GAC is a publicly available, web-based system for evaluating data obtained from peer-reviewed studies of genetic changes in tumors associated with exposure to chemical, physical, or biological agents, as well as spontaneous tumors. In mice, mutations in Kras2 and Hras-1 were the most common events reported for lung and liver tumors, respectively, whether chemically induced or spontaneous. There was a significant difference in Kras2 mutation incidence for spontaneous versus induced mouse lung tumors and in Hras-1 mutation incidence and spectrum for spontaneous versus induced mouse liver tumors. The major gene changes reported for human lung and liver tumors were in KRAS2 (lung only) and TP53. The KRAS2 mutation incidence was similar for spontaneous and asbestos-induced human lung tumors, while the TP53 mutation incidence differed significantly. Aflatoxin B1, hepatitis B virus, hepatitis C virus, and vinyl chloride all caused TP53 mutations in human liver tumors, but the mutation spectrum for each agent differed. The incidence of KRAS2 mutations in human compared to mouse lung tumors differed significantly, as did the incidence of Hras and p53 gene mutations in human compared to mouse liver tumors. Differences observed in the mutation spectra for agent-induced compared to spontaneous tumors and similarities in spectra for structurally similar agents support the concept that mutation spectra can serve as a "fingerprint" of exposure based on chemical structure. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Alpha Gamma Technol Inc, Raleigh, NC 27609 USA. RP Dunnick, JK (reprint author), NIEHS, MD EC-35,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS; NIEHS NIH HHS [N43-ES-15477] NR 214 TC 28 Z9 30 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2006 VL 90 IS 2 BP 400 EP 418 DI 10.1093/toxsci/kfj101 PG 19 WC Toxicology SC Toxicology GA 023DQ UT WOS:000236106000015 PM 16410370 ER PT J AU Moroff, G Eichler, H Brand, A Kekomaki, R Kurtz, J Letowska, M Pamphilon, D Read, EJ Lecchi, LPL Reems, JA Sacher, R Seetharaman, S Takahashi, TA AF Moroff, G Eichler, H Brand, A Kekomaki, R Kurtz, J Letowska, M Pamphilon, D Read, EJ Lecchi, LPL Reems, JA Sacher, R Seetharaman, S Takahashi, TA CA BEST Collaborative TI Multiple-laboratory comparison of in vitro assays utilized to characterize hematopoietic cells in cord blood SO TRANSFUSION LA English DT Article ID NUCLEATED CELL; CD34(+) CELL; TRANSPLANTATION; ENUMERATION; BANKING; ENGRAFTMENT; SURVIVAL; GRAFT; STEM AB BACKGROUND: Understanding the variability in results obtained by multiple laboratories is important because cord blood units are distributed worldwide for transplantation. STUDY DESIGN AND METHODS: Four exercises were conducted by multiple laboratories to assess assay variability on nucleated cell (NC), mononuclear cell (MNC) by hematology analyzers [HAs], and CD34+ cell (flow cytometry) measurements. Exercise 1 was an intralaboratory exercise in which the reproducibility of cell measurements was determined. Exercises 2 and 3 involved the shipment of identical processed cord blood samples. In Exercise 2, laboratory-specific methods were utilized. In Exercise 3, two commercial CD34+ cell methods (Stem-Kit and TruCOUNT) were used. In Exercise 4, CD34+ cell levels were determined on repetitive regating of identical list-mode files. RESULTS: Intralaboratory reproducibility was highest for NC measurements and lowest for CD34+ cell measurements. In Exercise 2, all laboratories except one utilized HA with an impedance technology and determined comparable results for NC and MNC levels, whereas the other laboratory utilized a HA with an optical counting method. Substantial variation was observed on measuring CD34+ cells with ranges of 32 to 141, 32 to 66, and 25 to 116 CD34+ cells per mu L for the three identical samples. In Exercise 3, on the use of one specific commercial assay, the ranges of CD34+ levels were 214 to 411 and 62 to 178 cells per mu L for the two identical samples. Nearly all participating laboratories determined comparable CD34+ levels on the use of identical list-mode files. CONCLUSION: These studies indicate that substantial variability in CD34+ cell levels were determined with flow cytometry. The variability in NC and MNC levels was minimal with HA methodology. C1 Amer Red Cross, Jerome H Holland Lab Biomed Sci, Rockville, MD 20855 USA. Univ Heidelberg, Inst Transfus Med & Immunol Mannheim, Heidelberg, Germany. Sanquin Blood Bank, SW Reg, Leiden, Netherlands. Finnish Res Cross Blood Serv, Helsinki, Finland. Inst Hematol & Transfus Med, Warsaw, Poland. Univ Bristol, Inst Transfus Sci, Bristol, Avon, England. Natl Blood Serv, Bristol, Avon, England. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD USA. IRCCS, Fdn Policlin Mangiagalli & Regina Elena, Dept Transfus Med & Transplant Immunol, Milan, Italy. Puget Sound Blood Ctr, Seattle, WA 98104 USA. Univ Cincinnati, Med Ctr, Hoxworth Blood Ctr, Cincinnati, OH 45267 USA. Univ Tokyo, Inst Med Sci, Div Cell Proc, Tokyo, Japan. RP Moroff, G (reprint author), Amer Red Cross, Jerome H Holland Lab Biomed Sci, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM moroff@usa.redcross.org RI Porretti, Laura/J-6748-2015 OI Porretti, Laura/0000-0001-8100-4262 NR 20 TC 20 Z9 20 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 APR PY 2006 VL 46 IS 4 BP 507 EP 515 DI 10.1111/j.1537-2995.2006.00758.x PG 9 WC Hematology SC Hematology GA 026HD UT WOS:000236329100005 PM 16584425 ER PT J AU Stevens, WT Bolan, CD Oblitas, JM Stroncek, DF Bennett, JE Leitman, SF AF Stevens, WT Bolan, CD Oblitas, JM Stroncek, DF Bennett, JE Leitman, SF TI Streptococcus agalactiae sepsis after transfusion of a plateletpheresis concentrate: benefit of donor evaluation SO TRANSFUSION LA English DT Article ID BACTERIAL-CONTAMINATION; SEPTICEMIA AB BACKGROUND: Bacterial contamination of platelet (PLT) components is an important cause of transfusion reactions. Recent efforts have focused on heightened surveillance to detect contamination before transfusion to limit recipient morbidity and mortality. Although identifying the cause of contamination is most often viewed in the context of recipient safety, this case illustrates the importance of a thorough evaluation on donor safety. CASE REPORT: A 68-year-old woman experienced a severe febrile reaction after a plateletpheresis transfusion. Blood cultures from the patient and from the plateletpheresis component were both positive for the presence of Streptococcus agalactiae. No abnormalities were identified on review of collection and processing records. The donor was asymptomatic and had a negative review of systems, a normal physical exam, normal laboratory values, and negative blood and urine cultures. One of three stool samples was positive for the presence of occult blood. Colonoscopy revealed a Dukes Stage B colonic adenocarcinoma. Fifteen months after surgical resection and adjuvant chemotherapy, the donor had no evidence of recurrent tumor. CONCLUSION: Identification of bacteria in blood components should trigger a comprehensive donor evaluation, particularly if donor bacteremia is suspected. Organisms that may be associated with an enteric source should prompt a thorough gastrointestinal evaluation. Because the primary reservoir of S. agalactiae in the human body is the gastrointestinal tract, and because no findings suggested an alternate portal of entry in our male donor, a gastrointestinal source was suspected. In this case, an evaluation for organism-specific pathology led to early identification of a potentially curable large bowel lesion. C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RP Leitman, SF (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C711,MSC 1184, Bethesda, MD 20892 USA. EM sleitman@mail.cc.nih.gov NR 15 TC 10 Z9 10 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 APR PY 2006 VL 46 IS 4 BP 649 EP 651 DI 10.1111/j.1537-2995.2006.00760.x PG 3 WC Hematology SC Hematology GA 026HD UT WOS:000236329100023 PM 16584443 ER PT J AU Miskin, R Masos, T Shoham, Z Williams-Simons, L AF Miskin, R Masos, T Shoham, Z Williams-Simons, L TI Urokinase-type plasminogen activator mRNA is expressed in normal developing teeth and leads to abnormal incisor enamel in alpha MUPA transgenic mice SO TRANSGENIC RESEARCH LA English DT Article DE enamel; proteolysis; teeth; development; uPA mRNA; urokinase-type plasminogen activator; alpha MUPA transgenic mice ID HEPATOCYTE GROWTH-FACTOR; TRANSFORMING GROWTH-FACTOR-BETA-1; EXTRACELLULAR PROTEOLYSIS; TOOTH MORPHOGENESIS; DEFICIENT MICE; CELL-SURFACE; MOUSE; MATRIX; SYSTEM; LOCALIZATION AB The urokinase-type plasminogen activator (uPA) is a secreted, inducible serine protease implicated in extracellular proteolysis and tissue remodeling. Here we detected uPA mRNA through in situ hybridization in developing molar and incisor teeth of normal mice at multiple sites of the cap and bell developmental stages. The mRNA was confined to epithelial cells, however, was undetectable in ameloblasts or their progenitor preameloblasts and the inner enamel epithelium. Furthermore, mice of five lines of previously described alpha MUPA transgenic mice, carrying a transgene consisting of the uPA cDNA linked downstream from the alpha A-crystallin promoter, overexpressed uPA mRNA in the same epithelial sites. In addition, alpha MUPA mice showed remarkably high levels of uPA mRNA in ameloblasts, however, exclusively in two specific sites late in incisor development. First, at the late secretory stage, but only on sides of the ameloblast layer. Second, in a limited zone of ameloblasts near the incisal end, coinciding with a striking morphological change of the ameloblast layer and the enamel matrix. In adult alpha MUPA mice, the incisor teeth displayed discoloration and tip fragility, and reduction of the outer enamel as determined by scanning electron microscopy. These results suggest that balanced uPA activity could play a role in normal tooth development. The alpha MUPA tooth phenotype demonstrates a remarkable sensitivity to excessive extracellular proteolysis at the incisor maturation stage of amelogenesis. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Miskin, R (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. EM ruth.miskin@weizmann.ac.il NR 52 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 J9 TRANSGENIC RES JI Transgenic Res. PD APR PY 2006 VL 15 IS 2 BP 241 EP 254 DI 10.1007/s11248-006-0006-3 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 031EB UT WOS:000236685800010 PM 16604464 ER PT J AU Garcia-Diaz, M Kunkel, TA AF Garcia-Diaz, M Kunkel, TA TI Mechanism of a genetic glissando: structural biology of indel mutations SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID HUMAN DNA-POLYMERASE; BASE-PAIR SUBSTITUTION; REPAIR PROTEIN MUTS; MISMATCH REPAIR; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; FRAMESHIFT MUTATIONS; REPLICATION FIDELITY; CRYSTAL-STRUCTURES; ACTIVE-SITE AB Insertions and deletions of bases in DNA (collectively termed 'indels') are both common and biologically relevant, being associated with different human pathologies including cancer and diseases associated with expansions of repeats. Four decades of research have resulted in several hypotheses regarding how indels are generated during DNA synthesis and how they subsequently undergo or escape correction. Recent structural studies of DNA polymerases bound to mutagenic substrates have increased our understanding of how DNA polymerases cope with abnormal substrates. These structures provide insight into the molecular mechanisms underlying indel generation. C1 NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Intramural NIH HHS NR 70 TC 87 Z9 88 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 2006 VL 31 IS 4 BP 206 EP 214 DI 10.1016/j.tibs.2006.02.004 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 038WG UT WOS:000237259600004 PM 16545956 ER PT J AU Hariri, AR Holmes, A AF Hariri, AR Holmes, A TI Genetics of emotional regulation: the role of the serotonin transporter in neural function SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID STRESSFUL LIFE EVENTS; 5-HT1A RECEPTOR-BINDING; ANXIETY-LIKE BEHAVIOR; DORSAL RAPHE NUCLEUS; MAJOR DEPRESSION; PROMOTER-POLYMORPHISM; PREFRONTAL CORTEX; HUMAN AMYGDALA; KNOCKOUT MICE; PSYCHIATRIC-DISORDERS AB Identifying biological mechanisms through which genes lead to individual differences in emotional behavior is paramount to our understanding of how such differences confer risk for neuro psychiatric illness. The emergence of techniques such as in vivo imaging of brain function in humans and genetic engineering in rodents has provided important new insights into the impact of serotonin (5-HT), a key modulator of emotional behavior, on neural systems subserving anxiety and depression. A major finding has been the discovery of genetic variation in a crucial regulatory molecule within the 5-HT system, the 5HT transporter (5-HTT), and its influence on emotional traits. The study of the 5-HTT provides a new foundation for understanding the neurobiological and genetic basis of emotional regulation and affective illness. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15213 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Hariri, AR (reprint author), Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. EM haririar@upmc.edu RI Hariri, Ahmad/D-5761-2011 NR 89 TC 397 Z9 407 U1 5 U2 68 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD APR PY 2006 VL 10 IS 4 BP 182 EP 191 DI 10.1016/j.tics.2006.02.011 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 037KG UT WOS:000237145000011 PM 16530463 ER PT J AU Margulies, EH Chen, CW Green, ED AF Margulies, EH Chen, CW Green, ED TI Differences between pair-wise and multi-sequence alignment methods affect vertebrate genome comparisons SO TRENDS IN GENETICS LA English DT Article ID INSIGHTS; DNA; IDENTIFICATION; DISCOVERY; ELEMENTS; BROWSER; REGIONS; TOOLS; UCSC AB Producing complete and accurate alignments of multiple genomic sequences is complex and prone to errors, especially with sequences generated from highly diverged species. In this article, we show that multi-sequence (as opposed to pair-wise) alignment methods are substantially better at aligning (or 'capturing') all of the available orthologous sequence from phylogenetically diverse vertebrates (i.e. those separated by relatively long branch lengths). Maximum gains are obtained only when sequences from many species are aligned. Such multi-sequence alignments contain significant amounts of exonic and highly conserved non-exonic sequences that are not captured in pair-wise alignments, thus illustrating the importance of the alignment method used for performing comparative genome analyses. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP Margulies, EH (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM elliott@nhgri.nih.gov; egreen@nhgri.nih.gov FU Intramural NIH HHS NR 25 TC 30 Z9 30 U1 2 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 2006 VL 22 IS 4 BP 187 EP 193 DI 10.1016/j.tig.2006.02.005 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 037KI UT WOS:000237145200002 PM 16499991 ER PT J AU Wahl, SM Wen, J Moutsopoulos, NM AF Wahl, SM Wen, J Moutsopoulos, NM TI The kiss of death: interrupted by NK-cell close encounters of another kind SO TRENDS IN IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; NATURAL-KILLER-CELLS; GROWTH-FACTOR-BETA; TGF-BETA; IMMUNOSUPPRESSION; INDUCTION; TOLERANCE; IMMUNITY; DISEASE AB An intimate but deadly encounter between natural killer (NK) cells and transformed cells results in the delivery of cytotoxic molecules into tumor cells. New evidence reveals another intimate association, this time between NK cells and regulatory T cells, but this encounter opposes NK-cell tumoricidal activity. Through a contact-dependent mechanism involving transforming growth factor-beta, regulatory T cells provide an escape mechanism from INK-cell-mediated tumor surveillance. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM srawahl@dir.nidcr.nih.gov FU Intramural NIH HHS NR 19 TC 15 Z9 17 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD APR PY 2006 VL 27 IS 4 BP 161 EP 164 DI 10.1016/J.IT.2006.02.002 PG 4 WC Immunology SC Immunology GA 037KN UT WOS:000237145700001 PM 16504582 ER PT J AU Meshorer, E Soreq, H AF Meshorer, E Soreq, H TI Virtues and woes of AChE alternative splicing in stress-related neuropathologies SO TRENDS IN NEUROSCIENCES LA English DT Review ID STRIATAL CHOLINERGIC INTERNEURONS; MESSENGER-RNA; ALZHEIMERS-DISEASE; HEAT-SHOCK; READTHROUGH ACETYLCHOLINESTERASE; GENE-EXPRESSION; CELL-NUCLEUS; IN-VIVO; BRAIN; GLUTAMATE AB The ACh hydrolyzing enzyme acetylcholinesterase (AChE) is a combinatorial series of proteins with variant N and C termini generated from alternate promoter usage and 3' alternative splicing. Neuronal AChE variants show indistinguishable enzymatic activity yet differ in their expression, multimeric assembly and membrane-association patterns. Differentially induced under stress, they show distinct non-hydrolytic properties and interact with different protein partners. Recent findings suggest that transcriptional and post-transcriptional regulation of AChE pre-mRNA is a neuroprotection strategy but might involve long-term damage. Specifically, variant-specific causal involvement of AChE in the progression of both neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) and neuromuscular syndromes (e.g. myasthenia gravis) raises the possibility that future therapeutic drugs might target specific AChE variant(s) or the corresponding RNA transcripts. C1 NCI, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, IL-91904 Jerusalem, Israel. Israel Ctr Neuronal Computat, Dept Biol Chem, IL-91904 Jerusalem, Israel. RP Meshorer, E (reprint author), NCI, NIH, Bldg 41,41 Lib Dr, Bethesda, MD 20892 USA. EM meshoree@mail.nih.gov; soreq@cc.huji.ac.il NR 79 TC 116 Z9 119 U1 1 U2 12 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD APR PY 2006 VL 29 IS 4 BP 216 EP 224 DI 10.1016/j.tins.2006.02.005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 037KE UT WOS:000237144800006 PM 16516310 ER PT J AU Miller, DL Taylor, SK Rotstein, DS Pough, MB Barr, MC Baldwin, CA Cunningham, M Roelke, M Ingram, D AF Miller, DL Taylor, SK Rotstein, DS Pough, MB Barr, MC Baldwin, CA Cunningham, M Roelke, M Ingram, D TI Feline immunodeficiency virus and puma lentivirus in Florida panthers (Puma concolor coryi): Epidemiology and diagnostic issues SO VETERINARY RESEARCH COMMUNICATIONS LA English DT Article DE cougar; feline immunodeficiency virus; FIV; Florida panther; KELA; puma lentivirus; PLV; peptide ELISA ID LINKED-IMMUNOSORBENT-ASSAY; CORONAVIRUS ANTIBODIES; SEQUENCE-ANALYSIS; INFECTION; CATS; ORGANIZATION; PREVALENCE; LEUKEMIA; IMMUNITY AB This study documents the seroprevalence of feline immunodeficiency virus (FIV) and puma lentivirus (PLV) in free-ranging and captive Florida panthers (Puma concolor coryi) (n = 51) and translocated Texas cougars (P. concolor stanleyana) (n = 10) from 1985 to 1998. The sera were tested for anti-FIV antibodies by enzyme-linked immunosorbent assay (ELISA) and Western blot tests. The ELISAs were read kinetically (KELA) and the sera were retrospectively examined by PLV peptide ELISA. Eleven panthers and one cougar were positive by KELA; 4 panthers and 4 cougars were equivocal; 35 panthers and 5 cougars were negative; and 1 panther had no data. Seven of the 11 KELA-positive panthers were also positive by Western blot tests and all but one were positive by PLV peptide ELISA. Ten KELA-negative and Western blot-negative cats, were positive by PLV peptide ELISA. KELA results varied within cats from one sample period to the next, but PLV peptide ELISA results were consistent. Territorial sympatry and mating behaviour, noted from radiotelemetry location data on the cats, may have contributed to viral transmission between seropositive animals. These findings suggest that Florida panthers and the introduced Texas cougars have been exposed to FIV and/or PLV. C1 Univ Georgia, Coll Vet Med, Vet Diagnost & Invest Lab, Tifton, GA 31793 USA. Florida Fish & Wildlife Conservat Commiss, Gainesville, FL USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN USA. Cornell Univ, Coll Vet Med, Dev Serol Diagnost Lab, Ithaca, NY 14853 USA. Western Univ Hlth Sci, Coll Vet Med, Pamona, CA USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Miller, DL (reprint author), Univ Georgia, Coll Vet Med, Vet Diagnost & Invest Lab, Tifton, GA 31793 USA. EM millerdl@uga.edu OI Miller, Debra/0000-0002-8544-174X NR 23 TC 2 Z9 2 U1 0 U2 12 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-7380 J9 VET RES COMMUN JI Vet. Res. Commun. PD APR PY 2006 VL 30 IS 3 BP 307 EP 317 DI 10.1007/s11259-006-3167-x PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 006VL UT WOS:000234925600010 PM 16437306 ER PT J AU Koonin, EV Dolja, VV AF Koonin, EV Dolja, VV TI Evolution of complexity in the viral world: The dawn of a new vision SO VIRUS RESEARCH LA English DT Article ID VIRUSES; ORIGIN AB Recent sequencing of the genomes of numerous large viruses provide for unprecedented opportunities to Study the emergence and evolution of complexity in the virus world. This special issue of Virus Research explores trends in the evolution of complex genomes in most major classes of viruses. Published by Elsevier B.V. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; doljav@science.oregonstate.edu NR 21 TC 33 Z9 35 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD APR PY 2006 VL 117 IS 1 BP 1 EP 4 DI 10.1016/j.virusres.2006.01.018 PG 4 WC Virology SC Virology GA 032AJ UT WOS:000236746000001 PM 16497406 ER PT J AU Prangishvill, D Garrett, RA Koonin, EV AF Prangishvill, D Garrett, RA Koonin, EV TI Evolutionary genomics of archaeal viruses: Unique viral genomes in the third domain of life SO VIRUS RESEARCH LA English DT Review DE crenarchacal viruses; virus evolution; hyperthermophiles; horizontal gene transfer ID PHAGE-PHI-H; INFECTING HALOBACTERIUM-CUTIRUBRUM; COMPLETE NUCLEOTIDE-SEQUENCE; HYPERTHERMOPHILIC ARCHAEA; STRUCTURAL PROTEINS; DNA RECOGNITION; TRANSCRIPTION REGULATION; HALOARCULA-HISPANICA; THERMOPROTEUS-TENAX; CRYSTAL-STRUCTURE AB In terms of virion morphology, the known viruses of archaea fall into two distinct classes: viruses of mesophilic and moderately thermophilic Eueryarchaeota closely resemble head-and-tail bacteriophages whereas viruses of hyperthermophilic Crenarchaeota show a variety of unique morphotypes. In accord with this distinction, the sequenced genomes of euryarchaeal viruses encode many proteins homologous to bacteriophage capsid proteins. In contrast. initial analysis of the crenarchaeal viral genomes revealed no relationships with bacteriophages and, generally, very few proteins with detectable homologs. Here we describe a re-analysis of the proteins encoded by archacal viruses, with an emphasis on comparative genomics of the unique viruses of Crenarchaeota. Detailed examination of conserved domains and motifs uncovered a significant number of previously unnoticed homologous relationships among the proteins of crenarchaeal viruses and between viral proteins and those from cellular life forms and allowed functional predictions for some of these conserved genes. A small pool of genes is shared by overlapping subsets of crenarchaeal viruses, in a general analogy with the metagenorne structure of bacteriophages. The proteins encoded by the genes belonging to this pool include predicted transcription regulators, ATPases implicated in viral DNA replication and packaging, enzymes of DNA precursor metabolism, RNA modification enzymes, and glycosylases. In addition, each of the crenarchaeal viruses encodes several proteins with prokaryotic but not viral homologs, some of which, predictably, seem to have been scavenged front the crenarchaeal hosts, but others might have been acquired from bacteria. We conclude that crenarchaeal viruses are, in general, evolutionarily unrelated to other known viruses and, probably, evolved via independent accretion of genes derived from the hosts and, through more complex routes of horizontal gene transfer, from other prokaryotes. Published by Elsevier B.V. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Inst Pasteur, Unite Biol Mol Gene Extremophiles, F-75724 Paris 15, France. Univ Copenhagen, Danish Archaea Ctr, Inst Mol Biol & Physiol, DK-1307 Copenhagen, Denmark. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Garrett, Roger/M-2450-2014 FU Intramural NIH HHS NR 127 TC 128 Z9 131 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD APR PY 2006 VL 117 IS 1 BP 52 EP 67 DI 10.1016/j.virusres.2006.01.007 PG 16 WC Virology SC Virology GA 032AJ UT WOS:000236746000005 PM 16503363 ER PT J AU Iyer, LA Balaji, S Koonin, EV Aravind, L AF Iyer, LA Balaji, S Koonin, EV Aravind, L TI Evolutionary genomics of nucleo-cytoplasmic large DNA viruses SO VIRUS RESEARCH LA English DT Review DE DNA viruses; evolution; poxvirus; capping enzyme; triphosphatase; iridovirus; coccolithovirus; phycodnavirus; primase; origin of viruses; DNA replication; origin of DNA replication; papain-like peptidase; sugar metabolism; ubiqutin signaling; growth factors; cytokine signaling; apoptosis ID HOLLIDAY JUNCTION RESOLVASES; MOLLUSCUM CONTAGIOSUM VIRUS; HORIZONTAL GENE-TRANSFER; HERPES-SIMPLEX VIRUS; NF-KAPPA-B; VACCINIA-VIRUS; TRANSCRIPTION FACTORS; GROUPER IRIDOVIRUS; UBIQUITIN LIGASE; MAMMALIAN-CELLS AB A previous comparative-genomic study of large nuclear and cytoplasmic DNA viruses (NCLDVs) of eukaryotes revealed the monophyletic origin of four viral families: poxviruses, asfarviruses, iridoviruses, and phycodnaviruses [Iyer, L.M., Aravind, L., Koonin, E.V., 2001. Common origin of four diverse families of large eukaryotic DNA viruses. J. Virol. 75 (23), 11720-11734]. Here we update this analysis by including the recently sequenced giant genome of the mimiviruses and several additional genomes of iridoviruses, phycodnaviruses, and poxviruses. The parsimonious reconstruction of the gene complement of the ancestral NCLDV shows that it was a complex virus with at least 41 genes that encoded the replication machinery, up to four RNA polymerase subunits, at least three transcription factors, capping and polyadenylation enzymes, the DNA packaging apparatus, and structural components of an icosahedral capsid and the viral membrane. The phylogeny of the NCLDVs is reconstructed by cladistic analysis of the viral gene complements, and it is shown that the two principal lineages of NCLDVs are comprised of poxviruses grouped with asfarviruses and iridoviruses grouped with phycodnaviruses-mimiviruses. The phycodna-mimivirus grouping was strongly supported by several derived shared characters, which seemed to rule out the previously suggested basal position of the mimivirus [Raoult, D., Audic, S., Robert, C., Abergel, C., Renesto, P., Ogata, H., La Scola, B., Suzan, M., Claverie, J.M. 2004. The 1.2-megabase genome sequence of Mimivirus. Science 306 (5700), 1344-1350]. These results indicate that the divergence of the major NCLDV families Occurred at an early stage of evolution, prior to the divergence of the major eukaryotic lineages. It is shown that subsequent evolution of the NCLDV genomes involved lineage-specific expansion of paralogous gene families and acquisition of numerous genes via horizontal gene transfer from the eukaryotic hosts, other viruses, and bacteria (primarily, endosymbionts and parasites). Amongst the expansions, there are multiple families of predicted virus-specific signaling and regulatory domains. Most NCLDVs have also acquired large arrays of genes related to ubiquitin signaling, and the animal viruses in particular have independently evolved several defenses against apoptosis and immune response, including growth factors and potential inhibitors of cytokine signaling. The mimivirus displays an enormous array of genes of bacterial provenance, including a representative of a new class of predicted papain-like peptidases. It is further demonstrated that a significant number of genes found in NCLDVs also have homologs in bacteriophages, although a vertical relationship between the NCLDVs and a particular bacteriophage group could not be established. On the basis of these observations, two alternative scenarios for the origin of the NCLDVs and other groups of large DNA viruses of eukaryotes are considered. One of these scenarios posits an early assembly of an already large DNA virus precursor from which various large DNA viruses diverged through an ongoing process of displacement of the original genes by xenologous or non-orthologous genes from various sources. The second scenario posits convergent emergence, on multiple occasions, of large DNA viruses from small plasmid-like precursors through independent accretion of similar sets of genes due to strong selective pressures imposed by their life cycles and hosts. Published by Elsevier B.V. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 148 TC 295 Z9 309 U1 10 U2 58 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD APR PY 2006 VL 117 IS 1 BP 156 EP 184 DI 10.1016/j.virusres.2006.01.009 PG 29 WC Virology SC Virology GA 032AJ UT WOS:000236746000013 PM 16494962 ER PT J AU Nguyen, HTT Amine, AB Lafitte, D Waheed, AA Nicoletti, C Villard, C Letisse, M Deyris, V Roziere, M Tchiakpe, L Danielle, CD Comeau, L Hiol, A AF Nguyen, HTT Amine, AB Lafitte, D Waheed, AA Nicoletti, C Villard, C Letisse, M Deyris, V Roziere, M Tchiakpe, L Danielle, CD Comeau, L Hiol, A TI Proteomic characterization of lipids rafts markers from the rat intestinal brush border SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE intestine; brush border; lipid rafts; proteomic; marker; GP2 ID GRANULE MEMBRANE-PROTEIN; GPI-ANCHORED PROTEINS; EPITHELIAL-CELLS; APICAL MEMBRANE; MICRODOMAINS; PURIFICATION; SECRETION; ENTEROCYTES; INVOLVEMENT; TRANSPORT AB To assess intestinal lipid rafts functions through the characterization of their protein markers, we have isolated lipid rafts of rat mucosa either from the total membrane or purified brush-border membrane (BBM) by sucrose gradient fractionation after detergent treatment. In both membrane preparations, the floating fractions (4-5) were enriched in cholesterol, ganglioside GM1, and N aminopeptidase (NAP) known as intestinal lipid rafts markers. Based on MALDI-TOF/MS identification and simultaneous detection by immunoblotting, 12 proteins from BBM cleared from contaminants were selected as rafts markers. These proteins include several signaling/trafficking proteins belonging to the G protein family and the annexins as well as GPI-anchored proteins. Remarkably GP2, previously described as the pancreatic granule GPI-anchored protein, was found in intestinal lipid rafts. The proteomic strategy assayed on the intestine leads to the characterization of known (NAP, alkaline phosphatase, dipeptidyl aminopeptidase, annexin II, and galectin-4) and new (GP2, annexin IV, XIIIb, G alpha(q), G alpha(11), glutamate receptor, and GPCR 7) lipid rafts markers. Together our results indicate that some digestive enzymes, trafficking and signaling proteins may be functionally distributed in the intestine lipid rafts. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Paul Cezanne, Fac Sci & Tech St Jerome, Inst Mediterraneen Rech Nutr, UMR INRA 1111,LCA LBBN, F-13397 Marseille 20, France. Univ Mediterranee, Fac Pharm, Lab Nutr & Dietet, Plateau Proteom UMR FRE 2727,27 Av J Moulin, F-13385 Marseille, France. Natl Canc Inst Frederick, HIV Drug Resistance Program, Virus Cell Interact Sect, Ft Detrick, MD 21702 USA. RP Hiol, A (reprint author), Univ Paul Cezanne, Fac Sci & Tech St Jerome, Inst Mediterraneen Rech Nutr, UMR INRA 1111,LCA LBBN, F-13397 Marseille 20, France. EM a.hiol@univ.u-3mrs.fr NR 36 TC 31 Z9 33 U1 1 U2 3 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 MAR 31 PY 2006 VL 342 IS 1 BP 236 EP 244 DI 10.1016/j.bbrc.2006.01.14 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 018VV UT WOS:000235793800032 PM 16480947 ER PT J AU Acker, MG Shin, BS Dever, TE Lorsch, JR AF Acker, MG Shin, BS Dever, TE Lorsch, JR TI Interaction between eukaryotic initiation factors 1A and 5B is required for efficient ribosomal subunit joining SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID START-SITE SELECTION; TRANSLATION INITIATION; PROTEIN-SYNTHESIS; ESCHERICHIA-COLI; TRANSFER-RNA; FACTOR IF2; FACTOR-II; IN-VIVO; BINDING; COMPLEX AB Eukaryotic initiation factor 5B ( eIF5B) is aGTPase that facilitates joining of the 60 S ribosomal subunit to the 40 S ribosomal subunit during translation initiation. Formation of the resulting 80 S initiation complex triggers eIF5B to hydrolyze its bound GTP, reducing the affinity of the factor for the complex and allowing it to dissociate. Here we present a kinetic analysis of GTP hydrolysis by eIF5B in the context of the translation initiation pathway. Our data indicate that stimulation of GTP hydrolysis by eIF5B requires the completion of early steps in translation initiation, including the eIF1- and eIF1A- dependent delivery of initiator methionyl- tRNA to the 40 S ribosomal subunit and subsequent GTP hydrolysis by eIF2. Full activation of GTP hydrolysis by eIF5B requires the extreme C terminus of eIF1A, which has previously been shown to interact with the C terminus of eIF5B. Disruption of either isoleucine residue in the eIF1A C- terminal sequence DIDDI reduces the rate constant for GTP hydrolysis by similar to 20- fold, whereas changing the aspartic acid residues has no effect. Changing the isoleucines in the C terminus of eIF1A also disrupts the ability of eIF5B to facilitate subunit joining. These data indicate that the interaction of the C terminus of eIF1A with eIF5B promotes ribosomal subunit joining and possibly provides a checkpoint for correct complex formation, allowing full activation of GTP hydrolysis only upon formation of a properly organized 80 S initiation complex. C1 Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Lorsch, JR (reprint author), Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, 725 N Wolfe St, Baltimore, MD 21205 USA. EM jlorsch@jhmi.edu OI Dever, Thomas/0000-0001-7120-9678; Lorsch, Jon/0000-0002-4521-4999 FU Intramural NIH HHS NR 34 TC 48 Z9 49 U1 0 U2 3 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 MAR 31 PY 2006 VL 281 IS 13 BP 8469 EP 8475 DI 10.1074/jbc.M600210200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100022 PM 16461768 ER PT J AU Fritz, TA Raman, J Tabak, LA AF Fritz, TA Raman, J Tabak, LA TI Dynamic association between the catalytic and lectin domains of human UDP-GalNAc : polypeptide alpha-N-acetylgalactosaminyltransferase-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACETYL-D-GALACTOSAMINE; N-ACETYLGALACTOSAMINYLTRANSFERASE FAMILY; O-LINKED GLYCOSYLATION; MUCIN TANDEM REPEAT; CRYSTAL-STRUCTURE; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; SUBSTRATE-SPECIFICITY; SEQUENCE ALIGNMENT; PEPTIDE SEQUENCE AB The family of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAcTs) is unique among glycosyltransferases, containing both catalytic and lectin domains that we have previously shown to be closely associated. Here we describe the x-ray crystal structures of human ppGalNAcT-2 (hT2) bound to the product UDP at 2.75 angstrom resolution and to UDP and an acceptor peptide substrate EA2 (PTTDSTTPAPTTK) at 1.64 angstrom resolution. The conformations of both UDP and residues Arg(362) - Ser(372) vary greatly between the two structures. In the hT2-UDP-EA2 complex, residues Arg(362) - Ser(373) comprise a loop that forms a lid over UDP, sealing it in the active site, whereas in the hT2-UDP complex this loop is folded back, exposing UDP to bulk solvent. EA2 binds in a shallow groove with threonine 7 positioned consistent with in vitro data showing it to be the preferred site of glycosylation. The relative orientations of the hT2 catalytic and lectin domains differ dramatically from that of murine ppGalNAcT-1 and also vary considerably between the two hT2 complexes. Indeed, in the hT2-UDP-EA2 complex essentially no contact is made between the catalytic and lectin domains except for the peptide bridge between them. Thus, the hT2 structures reveal an unexpected flexibility between the catalytic and lectin domains and suggest a new mechanism used by hT2 to capture glycosylated substrates. Kinetic analysis of hT2 lacking the lectin domain confirmed the importance of this domain in acting on glycopeptide but not peptide substrates. The structure of the hT2-UDP-EA2 complex also resolves long standing questions regarding ppGalNAcT acceptor substrate specificity. C1 NIDDK, Sect Biol Chem, NIH, Bethesda, MD 20892 USA. RP Tabak, LA (reprint author), NIDCR, NIH, Bldg 31,Room 2C39,31 Ctr Dr,MSC 2290, Bethesda, MD 20892 USA. EM tabakl@mail.nih.gov FU Intramural NIH HHS NR 49 TC 80 Z9 83 U1 1 U2 3 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 MAR 31 PY 2006 VL 281 IS 13 BP 8613 EP 8619 DI 10.1074/jbc.M513590200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100038 PM 16434399 ER PT J AU Wang, XL Ye, YH Lencer, W Hansen, TH AF Wang, XL Ye, YH Lencer, W Hansen, TH TI The viral E3 ubiquitin ligase mK3 uses the derlin/p97 endoplasmic reticulum-associated degradation pathway to mediate down-regulation of major histocompatibility complex class I proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-I; PEPTIDE-LOADING COMPLEX; ER-ASSOCIATED DEGRADATION; MEMBRANE-PROTEIN; IMMUNE EVASION; MISFOLDED PROTEINS; AAA-ATPASE; ANTIGEN PRESENTATION; FINGER PROTEIN; HEAVY-CHAINS AB Ubiquitin E3 ligases are important cellular components for endoplasmic reticulum (ER)- associated degradation due to their role in substrate-specific ubiquitination, which is required for retrotranslocation ( dislocation) of most unwanted proteins from the ER to the cytosol for proteasome degradation. However, our understanding of the molecular mechanisms of how E3 ligases confer substrate-specific recognition, and their role in substrate retrotranslocation is limited especially in mammalian cells. mK3 is a type III ER membrane protein encoded by murine gamma herpesvirus 68. As conferred by its N-terminal RING-CH domain, mK3 has E3 ubiquitin ligase activity. In its role as an immune evasion protein, mK3 specifically targets nascent major histocompatibility complex class I heavy chains (HC) for rapid degradation. The mechanism by which mK3 extracts HC from the ER membrane into the cytosol for proteasome-mediated degradation is unknown. Evidence is presented here that HC down-regulation by mK3 is dependent on the p97 AAA-ATPase. By contrast, the kK5 protein of Kaposi's sarcoma-associated herpesvirus is p97-independent despite the fact that it is highly homologous to mK3. mK3 protein was also found in physical association with Derlin1, an ER protein recently implicated in the retrotranslocation of HC by immune evasion protein US11, but not US2, of human cytomegalovirus. The mechanistic implications of these findings are discussed. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Ctr Digest Dis, Boston, MA 02115 USA. RP Hansen, TH (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM hansen@immunology.wustl.edu FU NIAID NIH HHS [AI19687] NR 51 TC 32 Z9 37 U1 0 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 MAR 31 PY 2006 VL 281 IS 13 BP 8636 EP 8644 DI 10.1074/jbc.M513920200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100041 PM 16446359 ER PT J AU Xu, Y Huang, S Liu, ZG Han, JH AF Xu, Y Huang, S Liu, ZG Han, JH TI Poly(ADP-ribose) polymerase-1 signaling to mitochondria in necrotic cell death requires RIP1/TRAF2-mediated JNK1 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; N-TERMINAL KINASE; APOPTOSIS-INDUCING FACTOR; RECEPTOR-INTERACTING PROTEIN; PERMEABILITY TRANSITION; CEREBRAL-ISCHEMIA; DNA-DAMAGE; PATHWAY; BCL-2; RIP AB Poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation-induced necrosis has been implicated in several pathophysiological conditions. Although mitochondrial dysfunction and apoptosis-inducing factor translocation from the mitochondria to the nucleus have been suggested to play very important roles in PARP-1-mediated cell death, the signaling events downstream of PARP-1 activation in initiating mitochondria dysfunction are not clear. Here we used the DNA alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine, a potent PARP-1 activator, to study PARP-1 activation-mediated cell death. We found, based on genetic knockouts and pharmacological inhibition, that c-Jun N-terminal kinase (JNK), especially JNK1, but not the other groups of mitogen-activated protein kinase, is required for PARP-1-induced mitochondrial dysfunction, apoptosis-inducing factor translocation, and subsequent cell death. We reveal that receptor-interacting protein 1 (RIP1) and tumor necrosis factor receptor-associated factor 2 (TRAF2), are upstream of JNK in PARP-1 hyperactivated cells, because PARP-1-induced JNK activation was attenuated in RIP1-/- and TRAF2-/- mouse embryonic fibroblast cells. Consistently, knockouts of RIP1 and TRAF2 caused a resistance to PARP-1-induced cell death. Therefore, our study uncovers that RIP1, TRAF2, and JNK comprise a pathway to mediate the signaling from PARP-1 overactivation to mitochondrial dysfunction. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Xu, Y (reprint author), Scripps Res Inst, Dept Immunol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM mcbxuyue@scripps.edu RI Han, J/G-4671-2010 FU NIAID NIH HHS [AI054796, AI41637]; NIGMS NIH HHS [GM37696, GM67101] NR 50 TC 160 Z9 164 U1 1 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 31 PY 2006 VL 281 IS 13 BP 8788 EP 8795 DI 10.1074/jbc.M508135200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100058 PM 16446354 ER PT J AU Peloponese, JM Jeang, KT AF Peloponese, JM Jeang, KT TI Role for Akt/protein kinase B and activator protein-1 in cellular proliferation induced by the human T-cell leukemia virus type 1 tax oncoprotein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTION FACTOR AP-1; I TAX; SIGNALING PATHWAY; GROWTH-FACTOR; HUMAN CANCER; C-FOS; PHOSPHATIDYLINOSITOL 3'-KINASE; TRANSGENIC MICE; TRANSFORMATION AB Human T-cell leukemia virus type 1 is an oncogenic retrovirus etiologically causal of adult T-cell leukemia. The virus encodes a Tax oncoprotein, which functions in transcriptional regulation, cell cycle control, and transformation. Because adult T-cell leukemia is a highly virulent cancer that is resistant to numerous chemotherapeutic treatments, to understand better this disease it is important to comprehend how human T-cell leukemia virus type 1 promotes cellular growth and survival. Most of the existing data point to Tax activation of NF-kappa B as important for cellular proliferation and transformation. We show here that Tax, in the absence of NF-kappa B signaling, can activate activator protein-1 to promote cellular proliferation and survival. Tax is shown to activate activator protein-1 through the phosphatidylinositol 3-kinase/Akt pathway. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 80 TC 60 Z9 60 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 MAR 31 PY 2006 VL 281 IS 13 BP 8927 EP 8938 DI 10.1074/jbc.M510598200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100073 PM 16436385 ER PT J AU Suh, JY Cai, ML Williams, DC Clore, GM AF Suh, JY Cai, ML Williams, DC Clore, GM TI Solution structure of a post-transition state analog of the phosphotransfer reaction between the A and B cytoplasmic domains of the mannitol transporter IIMannitol of the Escherichia coli phosphotransferase system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYL TRANSFER COMPLEX; POTATO CARBOXYPEPTIDASE INHIBITOR; NMR STRUCTURES; 3-DIMENSIONAL STRUCTURE; MOLECULAR-DYNAMICS; BACILLUS-SUBTILIS; DIPOLAR COUPLINGS; PROTEIN COMPLEXES; ACTIVE-SITE; ENZYME IIB AB The solution structure of the post-transition state complex between the isolated cytoplasmic A (IIA(Mtl)) and phosphorylated B (phospho-IIBMtl) domains of the mannitol transporter of the Escherichia coli phosphotransferase system has been solved by NMR. The active site His-554 of IIA(Mtl) was mutated to glutamine to block phosphoryl transfer activity, and the active site Cys-384 of IIBMtl ( residues of IIBMtl are denoted in italic type) was substituted by serine to permit the formation of a stable phosphorylated form of IIBMtl. The two complementary interaction surfaces are predominantly hydrophobic, and two methionines on IIBMtl, Met-388 and Met-393, serve as anchors by interacting with two deep pockets on the surface of IIA(Mtl). With the exception of a salt bridge between the conserved Arg-538 of IIA(Mtl) and the phosphoryl group of phospho-IIBMtl, electrostatic interactions between the two proteins are limited to the outer edges of the interface, are few in number, and appear to be weak. This accounts for the low affinity of the complex (K-d similar to 3.7 mM), which is optimally tuned to the intact biological system in which the A and B domains are expressed as a single polypeptide connected by a flexible 21-residue linker. The phosphoryl transition state can readily be modeled with no change in protein-protein orientation and minimal perturbations in both the backbone immediately adjacent to His-554 and Cys-384 and the side chains in close proximity to the phosphoryl group. Comparison with the previously solved structure of the IIA(Mtl)-HPr complex reveals how IIA(Mtl) uses the same interaction surface to recognize two structurally unrelated proteins and explains the much higher affinity of IIA(Mtl) for HPr than IIBMtl. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm B1-301, 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 51 TC 24 Z9 24 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 MAR 31 PY 2006 VL 281 IS 13 BP 8939 EP 8949 DI 10.1074/jbc.M513466200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100074 PM 16443929 ER PT J AU Thilo, C Berglund, P Applequist, SE Yewdell, JW Ljunggren, HG Achour, A AF Thilo, C Berglund, P Applequist, SE Yewdell, JW Ljunggren, HG Achour, A TI Dissection of the interaction of the human cytomegalovirus-derived US2 protein with major histocompatibility complex class I molecules - Prominent role of a single arginine residue in human leukocyte antigen-A2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL INHIBITORY RECEPTOR; GENE-PRODUCTS US2; HLA CLASS-I; CRYSTAL-STRUCTURE; HEAVY-CHAINS; ENDOPLASMIC-RETICULUM; BINDING-SITE; HOT-SPOTS; 3-DIMENSIONAL STRUCTURE; MEMBRANE-PROTEIN AB Human cytomegalovirus encodes several proteins that interfere with expression of major histocompatibility complex (MHC) class I molecules on the surface of infected cells. The unique short protein 2 (US2) binds to many MHC class I allomorphs in the endoplasmic reticulum, preventing cell surface expression of the class I molecule in question. The molecular interactions underlying US2 binding to MHC class I molecules and its allele specificity have not been fully clarified. In the present study, we first compared the sequences and the structures of US2 retained versus non-retained human leukocyte antigen (HLA) class I allomorphs to identify MHC residues of potential importance for US2 binding. On the basis of this analysis, 18 individual HLA-A2 mutants were generated and the ability of full-length US2 to bind wild-type and mutated HLA-A2 complexes was assessed. We demonstrate that Arg(181) plays a critical role in US2-mediated inhibition of HLA-A2 cell surface expression. The structural comparison of all known crystal structures of HLA-A2 either alone, or in complex with T cell receptor or the CD8 coreceptor, indicates that binding of US2 to HLA-A2 results in a unique, large conformational change of the side chain of Arg(181). However, although the presence of Arg(181) seems to be a prerequisite for US2 binding to HLA-A2, it is not sufficient for binding to all MHC class I alleles. C1 Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Achour, A (reprint author), Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden. EM adnane.achour@medhs.ki.se RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 64 TC 9 Z9 9 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 MAR 31 PY 2006 VL 281 IS 13 BP 8950 EP 8957 DI 10.1074/jbc.M507121200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 025EC UT WOS:000236247100075 PM 16452487 ER PT J AU Schwieters, CD Kuszewski, JJ Clore, GM AF Schwieters, CD Kuszewski, JJ Clore, GM TI Using Xplor-NIH for NMR molecular structure determination SO PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY LA English DT Review DE structure determination; NMR restraints; optimization; computational toolbox; proteins; nucleic acids ID NUCLEAR-MAGNETIC-RESONANCE; MACROMOLECULAR STRUCTURE DETERMINATION; PROTEIN-STRUCTURE DETERMINATION; PROTON DISTANCE CONSTRAINTS; RESIDUAL DIPOLAR COUPLINGS; COMPLETE CROSS-VALIDATION; STRUCTURE REFINEMENT; CHEMICAL-SHIFTS; MEAN-FORCE; X-RAY C1 NIH, Div COmputat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Schwieters, CD (reprint author), NIH, Div COmputat Biosci, Ctr Informat Technol, Bldg 12A, Bethesda, MD 20892 USA. EM charles.schwieters@nih.gov; mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 77 TC 370 Z9 377 U1 3 U2 59 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6565 J9 PROG NUCL MAG RES SP JI Prog. Nucl. Magn. Reson. Spectrosc. PD MAR 31 PY 2006 VL 48 IS 1 BP 47 EP 62 DI 10.1016/j.pnmrs.2005.10.001 PG 16 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Chemistry; Physics; Spectroscopy GA 035JL UT WOS:000236997000003 ER PT J AU Kaleeba, JAR Berger, EA AF Kaleeba, JAR Berger, EA TI Kaposi's sarcoma-associated herpesvirus fusion-entry receptor: Cystine transporter xCT SO SCIENCE LA English DT Article ID SURFACE HEPARAN-SULFATE; TARGET-CELLS; GENE-EXPRESSION; HUMAN-HERPESVIRUS-8; VIRUS; TAT; INDUCTION; PROTEIN; INFECTIVITY; DEPLETION AB Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is the causative agent of Kaposi's sarcoma and other lymphoproliferative syndromes often associated with HIV/AIDS. Functional complementary DNA selection for a receptor mediating KSHV cell fusion identified xCT, the 12-transmembrane light chain of the human cystine/glutamate exchange transporter system x(c)(-). Expression of recombinant xCT rendered otherwise not susceptible target cells permissive for both KSHV cell fusion and virion entry. Antibodies against xCT blocked KSHV fusion and entry with naturally permissive target cells. KSHV target cell permissiveness correlated closely with endogenous expression of xCT messenger RNA and protein in diverse human and nonhuman cell types. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM edward_berger@nih.gov FU Intramural NIH HHS NR 30 TC 85 Z9 91 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 MAR 31 PY 2006 VL 311 IS 5769 BP 1921 EP 1924 DI 10.1126/science.1120878 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 027BD UT WOS:000236387800044 PM 16574866 ER PT J AU Moaddel, R Wainer, IW AF Moaddel, R Wainer, IW TI Development of immobilized membrane-based affinity columns for use in the online characterization of membrane bound proteins and for targeted affinity isolations SO ANALYTICA CHIMICA ACTA LA English DT Article DE nicotinic receptors; drug transporters; affinity chromatography; displacement chromatography ID CHROMATOGRAPHIC STATIONARY PHASES; NICOTINIC ACETYLCHOLINE-RECEPTORS; P-GLYCOPROTEIN; NONCOMPETITIVE INHIBITORS; CONFORMATIONAL MOBILITY; COUPLED RECEPTOR; DRUG DISCOVERY; LIPID-MEMBRANE; BINDING; ALPHA-3-BETA-4 AB Membranes obtained from cell lines that express or do not express a target membrane bound protein have been immobilized on a silica-based liquid chromatographic Support or on the surface of an activated glass capillary. The resulting chromatographic Columns have been placed in liquid chromatographic systems and used to characterize the target proteins and to identify small molecules that bind to the target. Membranes containing ligand gated ion channels, G-protein Coupled receptors and drug transporters have been prepared and characterized. If a marker ligand has been identified for the target protein, frontal or zonal displacement chromatographic techniques can be used to determine binding affinities (K-d values) and non-linear chromatography can be used to assess the association (k(on)) and dissociation (k(off)) rate constants and the thermodynamics of the binding process. Membrane-based affinity Columns have been created using membranes from a cell line that does not express the target protein (control) and the same cell line that expresses the target protein (experimental) after genomic transfection. The resulting columns can be placed in a parallel chromatography system and the differential retention between the control and experimental columns can be used to identify small molecules and protein that bind to the target protein. These applications will be illustrated using columns created using cellular membranes containing nicotinic acetylcholine receptors and the drug transporter P-glycoprotein. (c) 2005 Elsevier B.V. All rights reserved. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov NR 36 TC 29 Z9 29 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD MAR 30 PY 2006 VL 564 IS 1 BP 97 EP 105 DI 10.1016/j.aca.2005.09.020 PG 9 WC Chemistry, Analytical SC Chemistry GA 030MZ UT WOS:000236640100013 PM 17723367 ER PT J AU Topol, IA Nemukhin, AV Salnikow, K Cachau, RE Abashkin, YG Kasprzak, KS Burt, SK AF Topol, IA Nemukhin, AV Salnikow, K Cachau, RE Abashkin, YG Kasprzak, KS Burt, SK TI Quantum chemical modeling of reaction mechanism for 2-oxoglutarate dependent enzymes: Effect of substitution of iron by nickel and cobalt SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR; NONHEME IRON; HIF-ALPHA; HYDROXYLATION; DIOXYGENASE; CLEAVAGE; PATHWAY; COMPLEX AB Enzymatic hydroxylation reactions carried Out by 2-oxoglutarate (2OG) dependent iron-containing oxygenases were recently implicated in oxyzgen sensing. In addition to oxygen depletion, two metals. cobalt and nickel, are capable of inducing hypoxic stress ill cells by inhibiting oxygenase activity. Two possible scenarios have been proposed for the explanation of the hypoxic effects of cobalt and nickel: oxidation of enzyme-bound iron following cobalt or nickel exposure, and substitution of iron by cobalt or nickel. Here. by using density functional theory calculations, we modeled the reaction route from the reaction components to the high-spin metal-oxide intermediate in the activation of oxygen molecule by 2OG-dependent enzymes for three metal ions Fe(II), Ni(II), and Co(II) in the active site. An initial molecular model was constructed based on the crystal structure of iron-containing asparaginyl hydroxylase (FIH-1). Nickel- and cobalt-containing enzymes were modeled by a consequent replacement of the iron in the active center. The energy profiles connecting stationary points on the potential surfaces were computed by using the intrinsic reaction coordinate (IRC) technique from the located transition states. The results of calculations show that the substitution of iron by nickel or cobalt modifies the reaction energy profile- however, qualitatively, the reaction mechanism remains essentially the same. Thus, we would postulate that if the iron ion in the active site were substitutable by nickel and/or cobalt ions enzyme activity Would be considerably altered due to high activation barriers. C1 NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. Russian Acad Sci, Inst Biochem Phys, Moscow 119997, Russia. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Topol, IA (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. RI Nemukhin, Alexander/P-9662-2015 FU NCI NIH HHS [N01-CO-12400] NR 21 TC 20 Z9 20 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD MAR 30 PY 2006 VL 110 IS 12 BP 4223 EP 4228 DI 10.1021/jp055633k PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 027HW UT WOS:000236407000010 PM 16553373 ER PT J AU Shaw, P Greenstein, D Lerch, J Clasen, L Lenroot, R Gogtay, N Evans, A Rapoport, J Giedd, J AF Shaw, P Greenstein, D Lerch, J Clasen, L Lenroot, R Gogtay, N Evans, A Rapoport, J Giedd, J TI Intellectual ability and cortical development in children and adolescents SO NATURE LA English DT Article ID FALSE DISCOVERY RATE; GENERAL INTELLIGENCE; CEREBRAL-CORTEX; HUMAN-BRAIN; MRI DATA; THICKNESS; POPULATION; CHILDHOOD; PEOPLE; VOLUME AB Children who are adept at any one of the three academic 'R's ( reading, writing and arithmetic) tend to be good at the others, and grow into adults who are similarly skilled at diverse intellectually demanding activities(1-3). Determining the neuroanatomical correlates of this relatively stable individual trait of general intelligence has proved difficult, particularly in the rapidly developing brains of children and adolescents. Here we demonstrate that the trajectory of change in the thickness of the cerebral cortex, rather than cortical thickness itself, is most closely related to level of intelligence. Using a longitudinal design, we find a marked developmental shift from a predominantly negative correlation between intelligence and cortical thickness in early childhood to a positive correlation in late childhood and beyond. Additionally, level of intelligence is associated with the trajectory of cortical development, primarily in frontal regions implicated in the maturation of intelligent activity(4,5). More intelligent children demonstrate a particularly plastic cortex, with an initial accelerated and prolonged phase of cortical increase, which yields to equally vigorous cortical thinning by early adolescence. This study indicates that the neuroanatomical expression of intelligence in children is dynamic. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20182 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, Bethesda, MD 20182 USA. EM shawp@mail.nih.gov RI Shaw, Philip/A-1129-2008; Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Staff, Roger/G-1826-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Staff, Roger/0000-0003-0620-8673; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS NR 30 TC 695 Z9 710 U1 17 U2 115 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 30 PY 2006 VL 440 IS 7084 BP 676 EP 679 DI 10.1038/nature04513 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 026OY UT WOS:000236350400045 PM 16572172 ER PT J AU Zarin, DA Tse, T Ide, NC AF Zarin, DA Tse, T Ide, NC TI Clinical trials report card - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20894 USA. RP Zarin, DA (reprint author), NIH, Bethesda, MD 20894 USA. EM dzarin@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 30 PY 2006 VL 354 IS 13 BP 1428 EP 1428 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 026KO UT WOS:000236338000029 ER PT J AU Zucker, DM Yang, S AF Zucker, DM Yang, S TI Inference for a family of survival models encompassing the proportional hazards and proportional odds models SO STATISTICS IN MEDICINE LA English DT Article DE survival analysis; transformation family (Box-Cox); frailty ID EFFICIENCY-ROBUST-TESTS; TRANSFORMATION MODELS; NUISANCE PARAMETER; REGRESSION-MODELS; CENSORED-DATA; TABLES AB For survival data regression, the Cox proportional hazards model is the most popular model, but in certain situations the Cox model is inappropriate. Various authors have proposed the proportional odds model as an alternative. Yang and Prentice recently presented a number of easily implemented estimators for the proportional odds model. Here we show how to extend the methods of Yang and Prentice to a family of survival models that includes the proportional hazards model and proportional odds model as special cases. The model is defined in terms of a Box-Cox transformation of the survival function, indexed by a transformation parameter rho. This model has been discussed by other authors, and is related to the Harrington-Fleming G(rho) family of tests and to frailty models. We discuss inference for the case where rho is known and the case where rho must be estimated. We present a simulation study of a pseudo-likelihood estimator and a martingale residual estimator. We find that the methods perform reasonably. We apply our model to a real data set. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Hebrew Univ Jerusalem, Dept Stat, IL-91905 Jerusalem, Israel. NHLBI, Rockledge Ctr 2, Off Biostat Res, Bethesda, MD 20892 USA. RP Zucker, DM (reprint author), Hebrew Univ Jerusalem, Dept Stat, Mt Scopus, IL-91905 Jerusalem, Israel. EM mszucker@mscc.huji.ac.il NR 27 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2006 VL 25 IS 6 BP 995 EP 1014 DI 10.1002/sim.2255 PG 20 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 020MY UT WOS:000235914800007 PM 16220492 ER PT J AU Ai, XJ Zhou, Z Bai, YW Choy, WY AF Ai, XJ Zhou, Z Bai, YW Choy, WY TI N-15 NMR spin relaxation dispersion study of the molecular crowding effects on protein folding under native conditions SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID STABILITY; KINETICS C1 Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. Natl Canc Inst, Lab Biochem, Bethesda, MD USA. RP Choy, WY (reprint author), Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. EM jchoy4@uwo.ca NR 12 TC 59 Z9 59 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 29 PY 2006 VL 128 IS 12 BP 3916 EP 3917 DI 10.1021/ja057832n PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 027GD UT WOS:000236401600034 PM 16551092 ER PT J AU Pan, YP Ma, BY Levine, AJ Nussinov, R AF Pan, YP Ma, BY Levine, AJ Nussinov, R TI Comparison of the human and worm p53 structures suggests a way for enhancing stability SO BIOCHEMISTRY LA English DT Article ID 2ND-SITE SUPPRESSOR MUTATIONS; DAMAGE-INDUCED APOPTOSIS; TUMOR-SUPPRESSOR; DNA-DAMAGE; CORE DOMAIN; MUTANT P53; CRYSTAL-STRUCTURE; GENE EVOLUTION; WILD-TYPE; PROTEIN AB Maintaining, the native conformation is essential for the proper function of tumor suppressor protein p53. However, p53 is a low-stability protein that can easily lose its function upon structural perturbations such as those resulting from missense Mutations, leading to the development of cancer. Therefore, it is important to develop strategies to design stable p53 which still maintains its normal function. Here, we compare the stabilities of the human and worm p53 core domains using molecular dynamics simulations. We find that the worm p53 is significantly more stable than the human form. Detailed analysis of the structural fluctuations shows that the stability difference lies in the peripheral structural motifs that contrast in their structural features and flexibility. The most dramatic difference in stability originates C from loop L1, from the turn between helix H1 and beta-strand S5, and from the turn that connects beta-strands S7 and S8. Structural analysis shows significant differences for these motifs between the two proteins. Loop L1 lacks secondary Structure, and the turns between helix H I and strand S5 and between strands S7 and S8 are much longer in the human form p53. On the basis of these differences, we designed a mutant by shortening the turn between strands S7 and S8 to enhance the stability. Surprisingly, this mutant was very stable when probed by molecular dynamics Simulations. In addition, the stabilization was not localized in the turn region. Loop L1 was also significantly stabilized. Our results show that stabilizing peripheral structural motifs can greatly enhance the stability of the p53 core domain and therefore is likely to be a viable alternative in the development of stable p53. In addition, loop- or turn-related mutants with different stabilities may also be used to probe the relationship between function, a particular structural motif, and its flexibility. C1 NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. Inst Adv Study, Princeton, NJ 08540 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 36 TC 18 Z9 18 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 28 PY 2006 VL 45 IS 12 BP 3925 EP 3933 DI 10.1021/bi052242n PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 028NT UT WOS:000236495400008 PM 16548519 ER PT J AU Padayatty, SJ Riordan, HD Hewitt, SM Katz, A Hoffer, LJ Levine, M AF Padayatty, SJ Riordan, HD Hewitt, SM Katz, A Hoffer, LJ Levine, M TI Intravenously administered vitamin C as cancer therapy: three cases SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID ASCORBIC-ACID THERAPY; RECOMMENDED DIETARY ALLOWANCE; TRANSITIONAL-CELL CARCINOMA; TERMINAL HUMAN CANCER; ALTERNATIVE MEDICINE; ORTHOMOLECULAR TREATMENT; SUPPLEMENTAL ASCORBATE; SUPPORTIVE TREATMENT; SURVIVAL TIMES; BLADDER-CANCER AB Early clinical studies showed that high-dose vitamin C, given by intravenous and oral routes, may improve symptoms and prolong life in patients with terminal cancer. Double-blind placebo-controlled studies of oral vitamin C therapy showed no benefit. Recent evidence shows that oral administration of the maximum tolerated dose of vitamin C (18 g/d) produces peak plasma concentrations of only 220 mu mol/L, whereas intravenous administration of the same dose produces plasma concentrations about 25-fold higher. Larger doses (50 - 100 g) given intravenously may result in plasma concentrations of about 14 000 mu mol/L. At concentrations above 1000 mu mol/L, vitamin C is toxic to some cancer cells but not to normal cells in vitro. We found 3 well-documented cases of advanced cancers, confirmed by histopathologic review, where patients had unexpectedly long survival times after receiving high-dose intravenous vitamin C therapy. We examined clinical details of each case in accordance with National Cancer Institute (NCI) Best Case Series guidelines. Tumour pathology was verified by pathologists at the NCI who were unaware of diagnosis or treatment. In light of recent clinical pharmacokinetic findings and in vitro evidence of anti-tumour mechanisms, these case reports indicate that the role of high-dose intravenous vitamin C therapy in cancer treatment should be reassessed. C1 NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. McGill Univ, Lady Davis Inst Med Res, Montreal, PQ H2W 1S4, Canada. Biocommun Res Inst, Wichita, KS USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, Natl Inst Hlth, Bldg 10,Rm 4D52-MSC 1372, Bethesda, MD 20892 USA. EM MarkL@mail.nih.gov RI Padayatty, Sebastian/A-8581-2012; OI Padayatty, Sebastian/0000-0001-8758-3170; Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK054506] NR 50 TC 99 Z9 104 U1 2 U2 19 PU CMA MEDIA INC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD MAR 28 PY 2006 VL 174 IS 7 BP 937 EP 942 DI 10.1503/cmaj.050346 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 023YB UT WOS:000236161000012 PM 16567755 ER PT J AU Lo, PHY Leung, ACC Xiong, WJ Law, S Duh, FM Lerman, MI Stanbridge, EJ Lung, ML AF Lo, PHY Leung, ACC Xiong, WJ Law, S Duh, FM Lerman, MI Stanbridge, EJ Lung, ML TI Expression of candidate chromosome 3p21.3 tumor suppressor genes and down-regulation of BLU in some esophageal squamous cell carcinomas SO CANCER LETTERS LA English DT Article DE 3p21.3; BLU; esophageal squamous cell carcinoma; tumorigenicity ID HOMOZYGOUS DELETION REGION; NASOPHARYNGEAL CARCINOMA; EPIGENETIC INACTIVATION; MICROCELL HYBRIDS; FREQUENT LOSS; LUNG-CANCER; SCID MICE; RASSF1A; 3P; HUMAN-CHROMOSOME-3 AB dThe expression of six chromosome 3p21.3 candidate tumor suppressor genes (BLU, FUS2, HYAL2, NPRL2, RASSF1A, and SEMA3B) in esophageal squamous cell carcinoma (ESCC) has been investigated. Reduced expression of BLU was detected in some ESCC cell lines and tumor tissues and the difference was quantitated by real-time quantitative polymerase chain reaction. Methylation specific-PCR revealed the down-regulation of BLU by epigenetic inactivation. However, exogeneous expression of BLU did not functionally suppress tumofigenicity in nude mice. These results suggest that over-expression of BLU alone is not sufficient to inhibit tumorigenicity. Further studies on BLU interacting proteins are required to elucidate the possible role of BLU in the development of ESCC. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Hong Kong Univ Sci & Technol, Dept Biol, Kowloon, Hong Kong, Peoples R China. Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China. SAIC Frederick Inc, NCI, Basic Res Program, Frederick, MD USA. NCI, Immunobiol Lab, Frederick, MD 21701 USA. Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. RP Lung, ML (reprint author), Hong Kong Univ Sci & Technol, Dept Biol, Clear Water Bay, Kowloon, Hong Kong, Peoples R China. EM bomaria@ust.hk RI Law, Simon/C-4324-2009 NR 32 TC 12 Z9 12 U1 0 U2 0 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 MAR 28 PY 2006 VL 234 IS 2 BP 184 EP 192 DI 10.1016/j.canlet.2005.03.036 PG 9 WC Oncology SC Oncology GA 030UV UT WOS:000236661400009 ER PT J AU Menon, V Sarnak, MJ Greene, T Wang, XL Pereira, AA Beck, GJ Kusek, JW Selhub, J Collins, AJ Levey, AS Shlipak, MG AF Menon, V Sarnak, MJ Greene, T Wang, XL Pereira, AA Beck, GJ Kusek, JW Selhub, J Collins, AJ Levey, AS Shlipak, MG TI Relationship between homocysteine and mortality in chronic kidney disease SO CIRCULATION LA English DT Article DE kidney; mortality; epidemiology ID CORONARY-HEART-DISEASE; PLASMA TOTAL HOMOCYSTEINE; FACTOR INTERVENTION TRIAL; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; HEMODIALYSIS-PATIENTS; SERUM HOMOCYSTEINE; FOLLOW-UP; TRANSPLANT RECIPIENTS AB Background - The relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4. Methods and Results - The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline ( n = 804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles ( < 14.7, 14.7 to 19.5, >= 19.6 mu mol/L) and as a continuous variable ( per 10/mu mol/L). Participants had a mean age of 52 +/- 12 years and glomerular filtration rate (GFR) of 33 +/- 12 mL/min per 1.73 m(2); 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause ( hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD ( HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR ( HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD ( 1.04, 0.85 to 1.27) mortality. Conclusions - Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function. C1 Tufts New England Med Ctr, Div Nephrol, Dept Med, Boston, MA USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA. Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Sarnak, MJ (reprint author), 750 Washington St,391, Boston, MA 02111 USA. EM msarnak@tufts-nemc.org FU NHLBI NIH HHS [R01 HL073208-01]; NIDDK NIH HHS [R01 DK066488-01, UO1 DK 35073, K23 DK02904, K23 DK067303] NR 43 TC 43 Z9 44 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 28 PY 2006 VL 113 IS 12 BP 1572 EP 1577 DI 10.1161/CIRCULATIONAHA.105.570127 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 025UO UT WOS:000236292600008 PM 16549639 ER PT J AU Edgar, R McKinstry, M Hwang, J Oppenheim, AB Fekete, RA Giulian, G Merril, C Nagashima, K Adhya, S AF Edgar, R McKinstry, M Hwang, J Oppenheim, AB Fekete, RA Giulian, G Merril, C Nagashima, K Adhya, S TI High-sensitivity bacterial detection using biotin-tagged phage and quantum-dot nanocomplexes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bacteriophage T7; BirA; Escherichia coli; water sample ID FLUORESCENT-BACTERIOPHAGE ASSAY; ESCHERICHIA-COLI O157-H7; IN-VIVO; CELLS; IDENTIFICATION; BIOTINYLATION; TUBERCULOSIS; PROTEINS AB With current concerns of antibiotic-resistant bacteria and biodefense, it has become important to rapidly identify infectious bacteria. Traditional technologies involving isolation and amplification of the pathogenic bacteria are time-consuming. We report a rapid and simple method that combines in vivo biotinylation of engineered host-specific bacteriophage and conjugation of the phage to streptavidin-coated quantum dots. The method provides specific detection of as few as 10 bacterial cells per milliliter in experimental samples, with an approximate to 100-fold amplification of the signal over background in 1 In. We believe that the method can be applied to any bacteria susceptible to specific phages and would be particularly useful for detection of bacterial strains that are slow growing, e.g., Mycobacterium, or are highly infectious, e.g., Bacillus anthracis. The potential for simultaneous detection of different bacterial species in a single sample and applications in the study of phage biology are discussed. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Opt Technol Div, Phys Lab, Gaithersburg, MD 20899 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. Ambion Inc, Austin, TX 78744 USA. NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Bldg 37,Room 5138, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov FU Intramural NIH HHS NR 18 TC 196 Z9 211 U1 9 U2 74 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 MAR 28 PY 2006 VL 103 IS 13 BP 4841 EP 4845 DI 10.1073/pnas.0601211103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500012 PM 16549760 ER PT J AU Bourgeois, D Vallone, B Arcovito, A Sciara, G Schotte, F Anfinrud, PA Brunori, M AF Bourgeois, D Vallone, B Arcovito, A Sciara, G Schotte, F Anfinrud, PA Brunori, M TI Extended subnanosecond structural dynamics of myoglobin revealed by Laue crystallography SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE heme proteins; conformational landscape; packing defects; functional control ID X-RAY CRYSTALLOGRAPHY; SPERM-WHALE MYOGLOBIN; MOLECULAR-DYNAMICS; LIGAND MIGRATION; CARBON-MONOXIDE; HEME-PROTEINS; CONFORMATIONAL RELAXATION; GEMINATE RECOMBINATION; CRYSTAL-STRUCTURE; CO BINDING AB Work carried out over the last 30 years unveiled the role of structural dynamics in controlling protein function. Cavity networks modulate structural dynamics trajectories and are functionally relevant; in globins they have been assigned a role in ligand migration and docking. These findings raised renewed interest for time-resolved structural investigations of myoglobin (Mb), a simple heme protein displaying a photosensitive iron-ligand bond. Photodissociation of MbCO generates a nonequilibrium population of protein structures relaxing over a time range extending from picoseconds to milliseconds. This process triggers ligand migration to matrix cavities with clear-cut effects on the rate and yield of geminate rebinding. Here, we report subnanosecond time-resolved Laue diffraction data on the triple mutant YQR-Mb [Leu-29(1310)Tyr, His-64(E7)Gln, Thr-67(E10)Arg] that depict the sequence of structural events associated with heme and protein relaxation from 100 ps to 316 ns and above. The photodissociated ligand rapidly (< 0.1 ns) populates the Xe-binding cavity distal to the heme. Moreover, the heme relaxation toward the deoxy configuration is heterogeneous, with a slower phase (approximate to ns) evident in these experiments. Damping of the heme response appears to result from a strain exerted by the E-helix via the CD-turn; Phe-43(CD1), in close contact with heme, opposes tilt until the strain is relieved. A comparison with crystallographic data on wild-type Mb and mutants Leu(29)Phe or Leu(29)Trp suggests that the internal structure controls the rate and amplitude of the relaxation events. A correlation between structural dynamics as unveiled by Laue crystallography and functional properties of Mb is presented. C1 Univ Roma La Sapienza, Dipartimento Sci Biochim, I-00185 Rome, Italy. Univ Roma La Sapienza, Ist Pasteur Fondazione Cenc Bolognetti, I-00185 Rome, Italy. Univ Grenoble 1, CEA, CNRS UMR 5075, Inst Biol Struct, F-38027 Grenoble, France. European Synchrotron Radiat Facil, F-38043 Grenoble, France. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Brunori, M (reprint author), Univ Roma La Sapienza, Dipartimento Sci Biochim, Piazzale A Moro 5, I-00185 Rome, Italy. EM maurizio.brunori@uniroma1.it RI Vallone, Beatrice/F-4174-2012; Arcovito, Alessandro/I-5552-2012; OI Arcovito, Alessandro/0000-0002-8384-4844; Brunori, Maurizio/0000-0002-7795-1635 FU Intramural NIH HHS NR 40 TC 85 Z9 86 U1 0 U2 11 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 MAR 28 PY 2006 VL 103 IS 13 BP 4924 EP 4929 DI 10.1073/pnas.0508880103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500026 PM 16547137 ER PT J AU Yu, L Wan, FY Dutta, S Welsh, S Liu, ZH Freundt, E Baehrecke, EH Lenardo, M AF Yu, L Wan, FY Dutta, S Welsh, S Liu, ZH Freundt, E Baehrecke, EH Lenardo, M TI Autophagic programmed cell death by selective catalase degradation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; necrosis; nonapoptotic; reactive oxygen species ID OXIDATIVE STRESS; APOPTOSIS; DAMAGE; ACTIVATION; MECHANISMS; INHIBITORS; DROSOPHILA; INDUCTION; CASPASES; BECLIN-1 AB Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. Recently, it has been shown that autophagy can induce cells to die; however, the mechanism of the autophagic cell death program is unclear. We now show that caspase inhibition leading to cell death by means of autophagy involves reactive oxygen species (ROS) accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Inhibition of autophagy by chemical compounds or knocking down the expression of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS accumulation and cell death. The cause of abnormal ROS accumulation is the selective autophagic degradation of the major enzymatic ROS scavenger, catalase. Caspase inhibition directly induces catalase degradation and ROS accumulation, which can be blocked by autophagy inhibitors. These findings unveil a molecular mechanism for the role of autophagy in cell death and provide insight into the complex relationship between ROS and nonapoptotic programmed cell death. C1 NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. Harvard Univ, Sch Med, Harvard Ctr Neurodegenerat & Repair, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England. RP Lenardo, M (reprint author), NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. EM lenardo@nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM59136, R01 GM059136, R56 GM059136] NR 48 TC 389 Z9 407 U1 5 U2 34 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 MAR 28 PY 2006 VL 103 IS 13 BP 4952 EP 4957 DI 10.1073/pnas.0511288103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500031 PM 16547133 ER PT J AU Wani, MA Haynes, LD Kim, J Bronson, CL Chaudhury, C Mohanty, S Waldmann, TA Robinson, JM Anderson, CL AF Wani, MA Haynes, LD Kim, J Bronson, CL Chaudhury, C Mohanty, S Waldmann, TA Robinson, JM Anderson, CL TI Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta 2-microglobulin gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE albumin; IgG; MHC class I; hypoalbuminemia; hypogammaglobulinemia ID CLASS-I PROTEINS; SIGNAL PEPTIDE; NEUROPEPTIDE-Y; HUMAN PLACENTA; IGG; CELLS; MICE; COMPLEX; ALBUMIN; IMMUNOGLOBULIN AB Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and IgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class 1 alpha-chain and beta(2)-microglobulin (beta(2)m) that binds two ligands, IgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately IgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the a-chain gene sequences of the siblings were normal, the beta M-2 genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble beta(2)m and HLA in the siblings' sera were <1% of normal. Transfection assays of beta(2)m-deficient cultured cells with beta(2)m cDNA indicated that the mutant beta(2)m supported <20% of normal expression Of beta(2)m, MIHC class 1, and FcRn proteins. We concluded that a beta(2)m gene mutation underlies the hypercatabolism and reduced serum levels of albumin and IgG in the two siblings with familial hypercatabolic hypoproteinemia. This experiment of nature affirms our hypothesis that FcRn binds IgG and albumin, salvages both from a degradative fate, and maintains their physiologic concentrations. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Surg, Madison, WI 53792 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Dept Cell Biol & Physiol, Columbus, OH 43210 USA. RP Anderson, CL (reprint author), NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov; anderson.48@osu.edu FU Intramural NIH HHS; NCI NIH HHS [CA88053, R01 CA088053]; NIAID NIH HHS [AI57530, R01 AI057530]; NICHD NIH HHS [HD38764, R01 HD038764] NR 25 TC 70 Z9 71 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2006 VL 103 IS 13 BP 5084 EP 5089 DI 10.1073/pnas.0600548103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500053 PM 16549777 ER PT J AU Garcia-Fresco, GP Sousa, AD Pillai, AM Moy, SS Crawley, JN Tessarollo, L Dupree, JL Bhat, MA AF Garcia-Fresco, GP Sousa, AD Pillai, AM Moy, SS Crawley, JN Tessarollo, L Dupree, JL Bhat, MA TI Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE myelin; paranodes; cerebellum; ataxia ID MYELIN-ASSOCIATED GLYCOPROTEIN; PROTEIN CASPR; PARANODAL JUNCTIONS; CNS MYELIN; TRANSPORT; MICE; DOMAINS; COMPLEX; RANVIER; NODES AB Axo-glial junctions (AGJs) play a critical role in the organization and maintenance of molecular domains in myelinated axons. Neurexin IV/Caspr1/paranodin (NCP1) is an important player in the formation of AGJs because it recruits a paranodal complex implicated in the tethering of glial proteins to the axonal membrane and cytoskeleton. Mice deficient in either the axonal protein NCP1 or the glial ceramide galactosyltransferase (CGT) display disruptions in AGJs and severe ataxia. in this article, we correlate these two phenotypes and show that both NCP1 and CGT mutants develop large swellings accompanied by cytoskeletal disorganization and degeneration in the axons of cerebellar Purkinje neurons. We also show that all spectrin is part of the paranodal complex and that, although not properly targeted, this complex is still formed in CGT mutants. Together, these findings establish a physiologically relevant link between AGJs and axonal cytoskeleton and raise the possibility that some neurodegenerative disorders arise from disruption of the AGJs. C1 Univ N Carolina, Sch Med, Curriculum Neurobiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Ctr Neurosci, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. NCI, Neural Dev Grp, Frederick, MD 21702 USA. Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. RP Bhat, MA (reprint author), Univ N Carolina, Sch Med, Curriculum Neurobiol, Chapel Hill, NC 27599 USA. EM manzoor_bhat@med.unc.edu OI Sousa, Aurea/0000-0002-9153-7414 FU NCI NIH HHS [CA78437]; NIGMS NIH HHS [GM63074, R01 GM063074] NR 48 TC 53 Z9 54 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2006 VL 103 IS 13 BP 5137 EP 5142 DI 10.1073/pnas.0601082103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500062 PM 16551741 ER PT J AU Storey, NM Gentile, S Ullah, H Russo, A Muessel, M Erxleben, C Armstrong, DL AF Storey, NM Gentile, S Ullah, H Russo, A Muessel, M Erxleben, C Armstrong, DL TI Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuronal development; phosphatidylinositol 3-kinase; potassium channels; Rac; KCNH2 ID VENTRICULAR MYOCYTES; POTASSIUM CHANNEL; MOLECULAR-BASIS; ACTIVATION; KINASE; RESISTANCE; HERG; HYPERACTIVITY; PROTEINS; ESTROGEN AB Many nuclear hormones have physiological effects that are too rapid to be explained by changes in gene expression and are often attributed to unidentified or novel G protein-coupled receptors. Thyroid hormone is essential for normal human brain development, but the molecular mechanisms responsible for its effects remain to be identified. Here, we present direct molecular evidence for potassium channel stimulation in a rat pituitary cell line (GH(4)C(1)) by a nuclear receptor for thyroid hormone, TR beta, acting rapidly at the plasma membrane through phosphatidylinositol 3-kinase (PI3K) to slow the deactivation of KCNH2 channels already in the membrane. Signaling was disrupted by heterologous expression of TR beta receptors with mutations in the ligand-binding domain that are associated with neurological disorders in humans, but not by mutations that disrupt DNA binding. More importantly, PI3K-dependent signaling was reconstituted in cell-free patches of membrane from CHO cells by heterologous expression of human KCNH2 channels and TR beta, but not TR alpha, receptors. TR beta signaling through PI3K provides a molecular explanation for the essential role of thyroid hormone in human brain development and adult lipid metabolism. C1 Natl Inst Environm Hlth Sci, Neurobiol Lab, Membrane Signaling Grp, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. RP Armstrong, DL (reprint author), Natl Inst Environm Hlth Sci, Neurobiol Lab, Membrane Signaling Grp, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. EM armstro3@niehs.nih.gov FU Intramural NIH HHS NR 36 TC 69 Z9 72 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2006 VL 103 IS 13 BP 5197 EP 5201 DI 10.1073/pnas.0600089103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500072 PM 16549781 ER PT J AU Gentile, S Darden, T Erxleben, C Romeo, C Russo, A Martin, N Rossie, S Armstrong, DL AF Gentile, S Darden, T Erxleben, C Romeo, C Russo, A Martin, N Rossie, S Armstrong, DL TI Rac GTPase signaling through the PP5 protein phosphatase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE KCNH2; tetratricopeptide repeat; neuronal development; potassium channel; thyroid hormone ID TETRATRICOPEPTIDE REPEAT DOMAIN; RHO-FAMILY PROTEINS; POTASSIUM CHANNEL; TPR DOMAIN; ACTIVATION; PROTEIN-PHOSPHATASE-5; SENSITIVITY; INHIBITION; KINASES; BINDING AB We have investigated the Rac-dependent mechanism of KCNH2 channel stimulation by thyroid hormone in a rat pituitary cell line, GH(4)C(1), with the patch-clamp technique. Here we present physiological evidence for the protein serine/threonine phosphatase, PP5, as an effector of Rac GTPase signaling. We also propose and test a specific molecular mechanism for PP5 stimulation by Rac-GTP. Inhibition of PP5 with the microbial toxin, okadaic acid, blocked channel stimulation by thyroid hormone and by Rac, but signaling was restored by expression of a toxin-insensitive mutant of PP5, Y451A, which we engineered. PP5 is unique among protein phosphatases in that it contains an N-terminal regulatory domain with three tetratricopeptide repeats (TPR) that inhibit its activity. Expression of the TPR domain coupled to GFP blocked channel stimulation by the thyroid hormone. We also show that the published structures of the PP5 TPR domain and the TPR domain of p67, the Rac-binding subunit of NADPH oxidase, superimpose over 92 a carbons. Mutation of the PP5 TPR domain at two predicted contact points with Rac-GTP prevents the TPR domain from functioning as a dominant negative and blocks the ability of Y451A to rescue signaling in the presence of okadaic acid. PP5 stimulation by Rac provides a unique molecular mechanism for the antagonism of Rho-dependent signaling through protein kinases in many cellular processes, including metastasis, immune cell chemotaxis, and neuronal development. C1 Natl Inst Environm Hlth Sci, Environm Biol Program, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. RP Armstrong, DL (reprint author), Natl Inst Environm Hlth Sci, Environm Biol Program, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. EM armstro3@niehs.nih.gov OI Martin, Negin/0000-0003-3166-8989 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS031221, NS031221] NR 38 TC 24 Z9 27 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 MAR 28 PY 2006 VL 103 IS 13 BP 5202 EP 5206 DI 10.1073/pnas.060080103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 028FO UT WOS:000236472500073 PM 16549782 ER PT J AU Rapaka, RS Coates, PM AF Rapaka, RS Coates, PM TI Dietary supplements and related products: A brief summary SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT Workshop on Natureceuticals, Nutraceuticals, Herbal Botanicals, and Psychoactives - Drug Discovery and Drug-Drug Interactions CY NOV 05-07, 2004 CL Baltimore, MD SP Natl Inst Drug Abuse, Amer Assoc Pharmaceut Sci DE dietary supplements; nutraceuticals; complementary and alternate medicine; herbal products; herb-drug interactions; transporters; p-glycoprotein; curcumin tea AB We were gratified by the interest expressed in publishing a large number of presentations from the NIDA organized Workshop on "Natureceuticals (Natural Products), Nutraceuticals, Herbal Botanicals, Psychoactives: Drug Discovery and Drug-Drug Interactions". The number of manuscripts received necessitated two volumes of proceedings. In this brief summary of the second volume, we present an introduction to the roles of organizations such as National Center for Complementary and Alternate Medicine and Office of Dietary Supplements, both at the National Institutes of Health, and the Food and Drug Administration. These agencies are involved in research and regulation of dietary supplements and related products. Next, a brief summary of each of the fifteen articles is provided. The first four articles are related to regulatory and standardization aspects: issues related to botanicals (Khan); USP and dietary supplements (Stinivasan); dietary supplement reference materials (Sander et al.); and proposed cGMPs and the scientific basis behind the proposed regulations by FDA (Melethil). The next three articles relate to the methodologies employed in research: LC/MS for the pharmacokinetic analysis polyphenols from dietary supplements (Barnes et al.); proteomic analysis of grape seed extract (Kim et al.); and a nematode model, C elegans, in Alzheimer's and ginkgo biloba extract for mechanistic studies; another model, a hepatocyte tissue culture model for drug herbal interaction, is reviewed later and presented by Venkataramanan. The next four chapters are on specific dietary supplements: green tea and the polyphenolic catechins (Zaveri); curcumin (Maheswari et al.); tocotrienols (alpha-tocotrienol, Sen and Roy), gamma-tocotrienol (Sree Kumar et al.). This topic is followed by drug interaction studies: in vitro and in vivo assessment methodologies (Venkataramanan); flavonoid-drug interactions (Morris); MDR and CYP3A4-mediated drug-herb interaction (Pal and Mitra); and evidence-based examination of drug-herb interaction (Chavez and Chavez). Published by Elsevier B.V. C1 Natl Inst Drug Abuse, Chem & Physiol Syst Res Branch, Bethesda, MD 20892 USA. Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Rapaka, RS (reprint author), Natl Inst Drug Abuse, Chem & Physiol Syst Res Branch, Room 4282,MSC-9555,6001 Exeecutive Blvd, Bethesda, MD 20892 USA. EM rr82u@nih.gov NR 0 TC 25 Z9 26 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 27 PY 2006 VL 78 IS 18 BP 2026 EP 2032 DI 10.1016/j.lfs.2005.12.017 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 027XC UT WOS:000236448400002 PM 16497339 ER PT J AU Caillard, S Agodoa, LY Bohen, EM Abbott, KC AF Caillard, S Agodoa, LY Bohen, EM Abbott, KC TI Mveloma, Hodgkin disease, and lymphoid leukemia after renal transplantation: Characteristics, risk factors and prognosis SO TRANSPLANTATION LA English DT Article DE posttransplant lymphoproliferative disorders; immunosuppression; USRDS; Hodgkin disease; myeloma; lymphoid leukemia; non-Hodgkin's lymphoma; hepatitis C virus ID HEPATITIS-C VIRUS; EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; PLASMA-CELL MYELOMA; INFECTION; RECIPIENT; IMMUNOSUPPRESSION; MALIGNANCIES; CANCER; HCV AB Background. Hodgkin disease and myeloma were recently included in the classification of posttransplant lymphoproliferative disorder (PTLD). However, because their incidence is low, not much is known about their particular features. Methods. The incidence, characteristics, risk, and prognostic factors of myeloma, Hodgkin disease, and lymphoid leukemia using the United States Renal Data System from 1991 to 2000 among 66,159 Medicare patients were analyzed. Results. In all, 1,169 recipients developed a lymphoid disease: 823 (1.2%) non-Hodgkin's lymphomas (NHL), 160 (0.24%) myelomas, 60 (0.1%) Hodgkin lymphomas, and 126 (0.2%) lymphoid leukemias. Older age was associated with an increased risk of myeloma and leukemia. The incidence of hepatitis C virus infection was higher in recipients with myeloma (6.9 vs. 3.9%, P=0.05). Induction therapy was associated with a greater risk of myeloma and leukemia, but not Hodgkin disease. Azathioprine was associated with a lower risk of myeloma, and tacrolimus with a lower risk of Hodgkin disease. According to the type of malignancy, ten-year survival rates were significantly different: 42, 26, 55 and 39% respectively for NHL, myeloma, Hodgkin disease, and leukemia. Conclusion. These results support specific features and risk factors related to the occurrence of each type of lymphoid-proliferation and suggest for the first time a possible association between hepatitis C virus and myeloma in kidney transplant recipients. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil NR 30 TC 58 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 27 PY 2006 VL 81 IS 6 BP 888 EP 895 DI 10.1097/01.tp.0000203554.54242.56 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 027UK UT WOS:000236440900013 PM 16570013 ER PT J AU Besada, P Shin, DH Costanzi, S Ko, H Mathe, C Gagneron, J Gosselin, G Maddileti, S Harden, TK Jacobson, KA AF Besada, Pedro Shin, Dae Hong Costanzi, Stefano Ko, Hyojin Mathe, Christophe Gagneron, Julien Gosselin, Gilles Maddileti, Savitri Harden, T. Kendall Jacobson, Kenneth A. TI Structure activity relationship of uridine 5 '-diphosphate analogs at the human P2Y6 receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. Univ Montpellier 2, Lab Chim Organ Biomol Synthese, F-34095 Montpellier, France. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. EM pedrop@intra.niddk.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 125-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906344 ER PT J AU Bewley, CA AF Bewley, Carole A. TI Marine natural products as inhibitors and mechanistic probes in infectious diseases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 469-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125907473 ER PT J AU Bryant, S AF Bryant, Stephen TI PubChem: An information resource linking chemistry and biology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Natl Ctr Biotechnol, Natl Lib Med, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 80-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903619 ER PT J AU Caplen, N AF Caplen, Natasha TI RNAi in mammalian cells: Transcripts, targets and technology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Canc Res Ctr, Gene Silencing Sect, NIH, Bethesda, MD 20892 USA. EM ncaplen@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 162-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906380 ER PT J AU Cisneros, GA Piquemal, JP Gresh, N Darden, TA AF Cisneros, G. Andres Piquemal, Jean-Philip Gresh, Nohad Darden, Thomas A. TI Toward a force field based on density fitting SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. CNRS, FRE 2718, IFR Biomed, Lab Pharmacochim Mol, F-75700 Paris, France. EM cisnero1@niehs.nih.gov RI Cisneros, Gerardo/B-3128-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 126-COMP PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903663 ER PT J AU Das, D Maeda, K Tsuchiya, K Mitsuya, H AF Das, Debananda Maeda, Kenji Tsuchiya, Kiyoto Mitsuya, Hiroaki TI Structural model of CCR5 for the discovery of entry inhibitors for the therapeutic intervention of HIV-1 infection SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NHLBI, Lab Biophys Chem, Bethesda, MD 20892 USA. NCI, Expt Retrovirol Sect, Med Branch, Bethesda, MD 20892 USA. EM debdas@helix.nih.gov RI Tsuchiya, Kiyoto/L-8650-2013 OI Tsuchiya, Kiyoto/0000-0002-8233-6653 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 340-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903875 ER PT J AU Freed, EO AF Freed, Eric O. TI Antiviral activity of the cholesterol-binding compound amphotericin B methyl ester (Ame) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Frederick Canc Res & Dev Ctr, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM efreed@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 552-PHYS PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125908669 ER PT J AU Halperin, I Wolfson, H Nussinov, R AF Halperin, Inbal Wolfson, Haim Nussinov, Ruth TI Correlated mutations in the Cellulosome SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NCI, FCRDC, Ctr Canc Res Nanobiol Program, Basic Res Program,SAIC, Bethesda, MD USA. EM inbal@helix.stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 74-CELL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125900758 ER PT J AU Hanson, PR AF Hanson, Paul R. TI Metathesis strategies in synthesis: Phosphorus heterocycles and functional oligomers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Univ Kansas, Dept Chem, Ctr Excellence Chem Methodolog & Lib Dev, NIH, Lawrence, KS 66045 USA. EM phanson@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 45-ORGN PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125907045 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, Ferenc Basser, Peter J. Hecht, Anne Marie Geissler, Erik TI Similarities between the osmotic and scattering properties of synthetic and biopolymer gels SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, F-38041 Grenoble, France. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 398-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125909393 ER PT J AU Horkay, F Dimitriadis, EK Horkayne-Szakaly, I Lin, DC Basser, PJ AF Horkay, Ferenc Dimitriadis, Emilios K. Horkayne-Szakaly, Iren Lin, David C. Basser, Peter J. TI Osmotic and mechanical properties of cartilage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 27-MEDI PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906245 ER PT J AU Hou, JG Zheng, J Redman, AR Hon, YY Shamsi, SA AF Hou, Jingguo - Zheng, Jack Redman, Andrea R. Hon, Yuen Yi. Shamsi, Shahab A. TI Simultaneous chiral bioanalysis of warfarin and its monohydroxylated metabolites using micellar electrokinetic chromatography and capillary electrochromatography coupled to electrospray ionization mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. Georgia State Univ, Ctr Biotechnol & Drug Discovery, Atlanta, GA 30303 USA. Georgia State Univ, Ctr Clin, Dept Pharm, Natl Inst Hlth, Atlanta, GA 30303 USA. Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci 2, Macon, GA 31207 USA. EM jing62ce@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 93-ANYL PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125900200 ER PT J AU Ivanov, AA Jacobson, KA AF Ivanov, Andrei A. Jacobson, Kenneth A. TI Molecular dynamics simulation of the human P2Y14 receptor and study of ligand-receptor interactions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. EM ivanovan@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 217-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903754 ER PT J AU Jacobson, KA Kim, SK Ivanov, AA Costanzi, S AF Jacobson, Kenneth A. Kim, Soo-Kyung Ivanov, Andrei A. Costanzi, Stefano TI Modeling ligand interactions at adenosine and P2Y nucleotide recptors: Influence of ribose conformation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Mol Recongnit Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 104-COMP PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903641 ER PT J AU Jiang, JK Thomas, CJ Neumann, S Lu, XP Childress, J Gershengorn, MC AF Jiang, Jian-Kang Thomas, Craig J. Neumann, Susanne Lu, Xinping Childress, John Gershengorn, Marvin C. TI Syntheses and biological activities of small molecules at thyrotropin-releasing hormone (TRH) receptors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM jiankangj@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 401-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906616 ER PT J AU London, RE Gabel, SA Kirby, TW Bose-Basu, B DeRose, EF Gao, GH Mueller, GA Beard, WA Wilson, SH AF London, Robert E. Gabel, Scott A. Kirby, Thomas W. Bose-Basu, Bidisha DeRose, Eugene F. Gao, Guanghua Mueller, Geoffrey A. Beard, William A. Wilson, Samuel H. TI Selective isotopic labeling in macromolecular NMR studies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, ITSS Contract, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 331-COMP PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903866 ER PT J AU Marquez, VE AF Marquez, Victor E. TI The pseudorotational cycle as a tool for drug design and discovery SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Med Chem Lab, CCR, NCIF,NIH, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 1-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125900555 ER PT J AU Metaferia, BB Bewley, CA AF Metaferia, Belhu B. Bewley, Carole A. TI Synthesis and biological evaluations of non-natural macrolides using ring closing olefin metathesis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM belhum@intra.niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 50-MEDI PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906268 ER PT J AU Mishra, SH Germann, MW Darby, MK AF Mishra, Subrata H. Germann, Markus W. Darby, Martyn K. TI Design and analysis of HIV RRE RNA targeting zinc finger proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. NIEHS, Res Triangle Pk, NC 27709 USA. EM smishra3@gsu.edu RI German, Markus/L-1531-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 383-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906598 ER PT J AU Moore, S Jaeschke, H Neumann, S Kleinau, G Costanzi, S Jiang, JK Childress, J Raaka, BM Colson, A Pashke, R Krause, G Thomas, CJ Gershengorn, MC AF Moore, Susanna Jaeschke, Holger Neumann, Susanne Kleinau, Gunnar Costanzi, Stefano Jiang, Jian-Kang Childress, John Raaka, Bruce M. Colson, Anny Pashke, Ralf Krause, Gerd Thomas, Craig J. Gershengorn, Marvin C. TI Synthesis, pharmacology and molecular modeling for the development of selective low molecular weight modulators for glycoprotein hormone receptors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Med Klin & Poliklin 3, D-7010 Leipzig, Germany. NIDDK Chem Biol Corp, Inst Mol Pharmacol, NIH, Bethesda, MD 20892 USA. EM mooresu@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 119-MEDI PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906338 ER PT J AU Morrell, A Antony, S Kohlhagen, G Pommier, Y Cushman, M AF Morrell, Andrew Antony, Smitha Kohlhagen, Glenda Pommier, Yves Cushman, Mark TI Synthesis of Benz[d]indeno[1,2-b]pyran-5,11-diones: Versatile intermediates for the design and synthesis of topoisomerase I inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM morrell@pharmacy.purdue.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 267-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906482 ER PT J AU Neckers, L AF Neckers, Len TI Is heat shock protein 90 the cancer chaperone? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM neckers@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 205-MEDI PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906422 ER PT J AU Newman, DJ AF Newman, David J. TI Natural products as leads to potential drugs: An old process or the new hope for drug discovery? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Natl Canc Inst, Nat Prod Branch, Fairview Ctr, Frederick, MD 21702 USA. EM dn22a@nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 467-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125907471 ER PT J AU Parmley, SM Morrell, A Agama, K Antony, S Pommier, Y Cushman, M AF Parmley, Seth M. Morrell, Andrew Agama, Keli Antony, Smitha Pommier, Y. Cushman, Mark TI Design and synthesis of optimized indenoisoquinolines as topoisomerase I inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Western Kentucky Univ, Dept Chem, Bowling Green, KY 42633 USA. Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Pirdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM seth.parmley@wku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 295-CHED PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125901291 ER PT J AU Perreira, M Kim, EJ Hanover, JA Thomas, CJ AF Perreira, Melissa Kim, Eun Ju Hanover, John A. Thomas, Craig J. TI Synthesis of PUGNAC analogs and the development of fluorogenic substrates toward the selective study of O-GlcNAcase SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDKD, Chem Biol Core Facil, NIH, Bethesda, MD 20982 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20982 USA. EM perreiramelissa@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 321-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906536 ER PT J AU Samarakoon, T Harned, AM Hanson, PR Flynn, DL AF Samarakoon, Thiwanka Harned, Andrew M. Hanson, Paul R. Flynn, Daniel L. TI High load soluble oligomeric triphenylphosphine: Applications in organic synthesis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Univ Kansas, Dept Chem, NIH, Ctr Excellence Chem Methodol & Lib Dev KUCMLD, Lawrence, KS 66045 USA. EM smtikiri@mail.ku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 132-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125907132 ER PT J AU Schwab, JM AF Schwab, John M. TI Engineered biosynthesis: A strategy for drug development and the NIH Roadmap SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIGMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 409-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906624 ER PT J AU Shi, ZD Worthy, KM Fisher, RJ Burke, TR AF Shi, Zhen-Dan Worthy, Karen M. Fisher, Robert J. Burke, Terrence R., Jr. TI Design and synthesis of triazole-containing macrocylclic tetrapeptide as novel Grb2 SH2 domain ligands SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD USA. EM shiz@ncifcrf.gov RI Fisher, Robert/B-1431-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 242-MEDI PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125906457 ER PT J AU Skoumbourdis, AP Feldman, KS AF Skoumbourdis, Amanda P. Feldman, Ken S. TI Total syntheses of the pyrrole-imidazole alkaloids dibromophakellstatin and dibromophakellin SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIDDK, Chem Biol Core Facil, Natl Inst Hlth, Bethesda, MD 20892 USA. Penn State Univ, Dept Chem, University Pk, PA 16802 USA. EM skoumbourdisa@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 443-ORGN PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125907447 ER PT J AU Vedantham, P Guerra, J Gor, PJ Zhang, MJ Jimenez, MD Georg, GI Hanson, PR AF Vedantham, Punitha Guerra, Jennifer Gor, Parul J. Zhang, Mianji del Sol Jimenez, Maria Georg, Gunda I. Hanson, Paul R. TI High-load ROMP-derived oligomers with tunable properties: Applications in library generation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 Univ Kansas, Dept Chem, NIH, Ctr Excellence Chem Methodol & Lib Dev KUCMLD, Lawrence, KS 66045 USA. EM punithav@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 135-ORGN PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125907135 ER PT J AU Veenstra, TD AF Veenstra, Timothy D. TI Identification of a functional biomarker for interstitial cystitis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 302-ANYL PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125900409 ER PT J AU Wainer, IW Moaddel, R Jozwiak, K AF Wainer, Irving W. Moaddel, Ruin Jozwiak, Krzysztof TI Nonlinear chromatography studies using immobilized nicotinic receptors for the determination of pharmacological properties SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NIA, Gerontol Res Ctr, LCI, Baltimore, MD 21224 USA. Med Univ Lublin, Dept Chem, Lublin, Poland. EM Wainerir@grc.nia.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 334-ANYL PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125900441 ER PT J AU Weidlich, I Nicklaus, MC AF Weidlich, Iwona Nicklaus, Marc C. TI Flexible docking of the inhibitors into Tyrosyl-DNA Phosphodiesterase (Tdp1) active sites SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Frederick, MD 21702 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. EM iweidlic@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 140-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903677 ER PT J AU Weidlich, I Nicklaus, MC AF Weidlich, Iwona Nicklaus, Marc C. TI Conformational study of small molecules in the protein environment SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 231st National Meeting of the American-Chemical-Society CY MAR 26-30, 2006 CL Atlanta, GA SP Amer Chem Soc C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM iweidlic@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2006 VL 231 MA 139-COMP PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 050YE UT WOS:000238125903676 ER PT J AU Khwaja, F Tabassum, A Allen, J Djakiew, DL AF Khwaja, F Tabassum, A Allen, J Djakiew, DL TI The p75(NTR) tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE p75(NTR); death domain; NGF; cell cycle suppression; apoptosis; TUNEL staining ID NERVE GROWTH-FACTOR; NEUROTROPHIN RECEPTOR P75(NTR); FACTOR-LIKE PROTEIN; SIGNAL-TRANSDUCTION; DEPENDENT KINASES; CANCER CELLS; EXPRESSION; DEATH; P75; ADENOCARCINOMA AB The p75 neurotrophin receptor (p75(NTR)) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75(NTR) retarded cell cycle progression by induced accumulation of cells in GO/GI and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (ADD) dominant-negative antagonist of p75(NTR) showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75(NTR)-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75(NTR) expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75(NTR) rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75(NTR) was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75(NTR)-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75(NTR) expressing prostate cancer cells. (c) 2006 Elsevier Inc. All rights reserved. C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. Toronto Western Hosp, Toronto, ON M5T 258, Canada. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Djakiew, DL (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA. EM djakiewd@georgetown.edu NR 45 TC 33 Z9 40 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 24 PY 2006 VL 341 IS 4 BP 1184 EP 1192 DI 10.1016/j.bbrc.2006.01.073 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 017NI UT WOS:000235699900041 PM 16460673 ER PT J AU Wei, W Lu, Q Chaudry, GJ Leppla, SH Cohen, SN AF Wei, W Lu, Q Chaudry, GJ Leppla, SH Cohen, SN TI The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin SO CELL LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; WNT SIGNALING PATHWAY; MAMMALIAN-CELLS; PROTECTIVE ANTIGEN; BETA-CATENIN; GENE FAMILY; ENDOCYTOSIS; MICE; AXIN; INACTIVATION AB Toxins, produced by Bacillus anthracis and other microbial pathogens require functions of host cell genes to yield toxic effects. Here we show that low density lipoprotein receptor-related protein 6 (LRP6), previously known to be a coreceptor for the Wnt signaling pathway, is required for anthrax toxin lethality in mammalian cells. Downregulation of LRP6 or coexpression of a truncated LRP6 dominant-negative peptide inhibited cellular uptake of complexes containing the protective antigen (PA) carrier of anthrax toxin moieties and protected targeted cells from death, as did antibodies against epitopes; in the LRP6 extracellular domain. Fluorescence microscopy and biochemical analyses showed that LRP6 enables toxin internalization by interacting at the cell surface with PA receptors TEM8/ATR and/or CMG2 to form a multicomponent complex that enters cells upon PA binding. Our results, which reveal a previously unsuspected biological role for LRP6, identify LRP6 as a potential target for countermeasures against anthrax toxin lethality. C1 Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. NIAID, Div Intramural Res, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, SN (reprint author), Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. EM sncohen@stanford.edu RI Chaudry, Ghulam/F-9761-2011 NR 51 TC 87 Z9 92 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 24 PY 2006 VL 124 IS 6 BP 1141 EP 1154 DI 10.1016/j.cell.2005.12.045 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038RS UT WOS:000237241400016 PM 16564009 ER PT J AU Mullen, GED Giersing, BK Ajose-Popoola, O Davis, HL Kothe, C Zhou, H Aebig, J Dobrescu, G Saul, A Long, CA AF Mullen, GED Giersing, BK Ajose-Popoola, O Davis, HL Kothe, C Zhou, H Aebig, J Dobrescu, G Saul, A Long, CA TI Enhancement of functional antibody responses to AMA1-C1/Alhydrogel (R), a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide SO VACCINE LA English DT Article DE AMA1; CPG; malaria vaccine ID APICAL MEMBRANE ANTIGEN-1; B SURFACE-ANTIGEN; IMMUNE-RESPONSES; PROTECTIVE IMMUNITY; POTENT ENHANCER; DNA; MICE; MOTIFS; IMMUNOGENICITY; MONKEYS AB Apical membrane antigen 1 (AMA1) has been shown to be a promising malaria vaccine candidate. The multiallelic AMA1-C1 vaccine currently in Phase I trials in the US and Mali contains an equal mixture of the ectodomain portion of recombinant AMA1 from the FVO and 3D7 clones of Plasmodium falciparum, formulated on Alhydrogel. It is hoped that inclusion of a human-optimized CpG oligodeoxynucleotide (ODN) (CPG 7909) with our existing AMA1-C1/Alhydrogel vaccine will lead to a higher concentration of functional AMA1-C1 antibodies. Preclinical studies were performed in mice, rats and guinea pigs to assess the safety, immunogenicity and functionality of the immune response to AMA1-C1 with Alhydrogel+CPG 7909 compared to antigen with Alhydrogel alone. Day 42 mean anti-AMA1 ELISA titer values derived from individual animals were compared between Alhydrogel and Alhydrogel + CPG 7909 groups at each antigen dose for each species. Sera from Alhydrogel + CPG 7909 groups displayed significantly higher antibody titers (P < 0.025) than their comparable Alhydrogel alone group. Mouse IgG isotype analysis showed that AMA1-C1/Alhydrogel induced a predominately Th2 type response while AMA1-C1/Alhydrogel + CPG 7909 gave a mixed Th1/Th2 type response. When tested for functional activity by in vitro inhibition of parasite invasion, IgG isolated from serum pools of AMA1-C1/Alhydrogel + CPG 7909 animals was more effective against both FVO and 3D7 parasites than an equal concentration of IgG from animals receiving vaccines adjuvanted with Alhydrogel alone. These promising preclinical results have recently led to the start of a Phase I trial in the US. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. Coley Pharmaceut Grp, Ottawa, ON, Canada. RP Mullen, GED (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM gmullen@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Intramural NIH HHS NR 38 TC 49 Z9 51 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 MAR 24 PY 2006 VL 24 IS 14 BP 2497 EP 2505 DI 10.1016/j.vaccine.2005.12.034 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IU UT WOS:000236259900006 PM 16434128 ER PT J AU Bartlett, EJ Amaro-Carambot, E Surman, SR Collins, PL Murphy, BR Skiadopoulos, MH AF Bartlett, EJ Amaro-Carambot, E Surman, SR Collins, PL Murphy, BR Skiadopoulos, MH TI Introducing point and deletion mutations into the P/C gene of human parainfluenza virus type 1 (HPIV 1) by reverse genetics generates attenuated and efficacious vaccine candidates SO VACCINE LA English DT Article DE human parainfluenza virus; attenuating mutations; interferon antagonist; vaccine candidates; non-human primate study ID RESPIRATORY SYNCYTIAL VIRUS; ACCESSORY C PROTEINS; L-POLYMERASE PROTEIN; VIRAL-RNA SYNTHESIS; ACUTE OTITIS-MEDIA; SENDAI-VIRUS; V-PROTEIN; WILD-TYPE; INTERFERON-BETA; YOUNG-CHILDREN AB The P/C gene of human parainfluenza virus type 1 (HPIV1) encodes a nested set of related accessory C proteins, C'/C/Y1/Y2, which have been shown in other paramyxoviruses to have a role in evasion of the type I interferon (IFN) response following virus infection. We previously demonstrated that a set of two amino acid substitutions, C-R84G/HNT553A, and a separate amino acid substitution, C-F170S, are independently attenuating for HPIV1 in African green monkeys (AGMs). However, in each case the attenuation (att) phenotype is vulnerable to reversion by a single nucleotide change back to wild type. Using reverse genetics, recombinant HPIV1 (rHPIV1) vaccine candidates were generated that were designed for increased genetic and phenotypic stability by: (i) creating a two-amino acid deletion and substitution at the site of the C-F170S mutation, yielding C-Delta 170; (ii) introducing a six amino acid deletion in the N-terminal region of C, CDelta 10-15; and (iii) combining these stable deletion mutations with the att C-R84G/HNT553A mutation. The resulting rHPIV1 vaccine candidates were evaluated for attenuation in hamsters and AGMs and for immunogenicity and protective efficacy in AGMs. The CDelta 10-15 mutation was attenuating in hamsters but not in AGMs, and likely will be of limited value for an HPIV1 vaccine. Conversely, the C-R84G/HNT553A mutation set was attenuating in AGMs but not in hamsters. Thus, these two mutations demonstrated reciprocal host range phenotypes involving different regions of C. The C-Delta 170 mutation conferred a significant level of attenuation in hamsters and AGMs that closely resembled that of C-F170S and will be of particular utility for vaccine development because it involves a deletion of six nucleotides rendering it highly refractory to reversion. The combination of the C-R84G/HNT153A mutation set and the C-Delta 170 deletion mutation yielded a virus, rC(R84G/Delta 170)HN(T553A), that exhibited a satisfactory level of attenuation in hamsters and AGMs and was immunogenic and highly protective against HPIV1 wt challenge. This virus will be evaluated clinically as a live intranasal HPIV1 vaccine, one that can be further attenuated as necessary by the introduction of additional stabilized att mutations previously developed in the L protein. Published by Elsevier Ltd. C1 NIAID, Infect Dis Lab, Resp Viruses Sect, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bartlett, EJ (reprint author), NIAID, Infect Dis Lab, Resp Viruses Sect, NIH,Dept Hlth & Human Serv, Bldg 50,Room 6511,50 S Dr MSC 8007, Bethesda, MD 20892 USA. EM EBartlett@niaid.nih.gov NR 62 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 24 PY 2006 VL 24 IS 14 BP 2674 EP 2684 DI 10.1016/j.vaccine.2005.10.047 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IU UT WOS:000236259900027 PM 16364511 ER PT J AU Di Santo, R Costi, R Roux, A Artico, M Lavecchia, A Marinelli, L Novellino, E Palmisano, L Andreotti, M Amici, R Galluzzo, CM Nencioni, L Palamara, AT Pommier, Y Marchand, C AF Di Santo, R Costi, R Roux, A Artico, M Lavecchia, A Marinelli, L Novellino, E Palmisano, L Andreotti, M Amici, R Galluzzo, CM Nencioni, L Palamara, AT Pommier, Y Marchand, C TI Novel bifunctional quinolonyl diketo acid derivatives as HIV-1 integrase inhibitors: Design, synthesis, biological activities, and mechanism of action SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CELL-BASED ASSAYS; CATALYTIC DOMAIN; STRAND TRANSFER; DRUG DESIGN; SITE; REPLICATION; BINDING; MULTIPLICATION; PROTEIN AB The virally encoded integrase protein is an essential enzyme in the life cycle of the HIV-1 virus and represents an attractive and validated tar get in the development of therapeutics against HIV infection. Drugs that selectively inhibit this enzyme, when used in combination with inhibitors of reverse transcriptase and protease, are believed to be highly effective in suppressing the viral replication. Among the HIV-1 integrase inhibitors, the beta-diketo acids (DKAs) represent a major lead for anti-HIV-1 drug development. In this study, novel bifunctional quinolonyl diketo acid derivatives were designed, synthesized, and tested for their inhibitory ability against HIV-1 integrase. The compounds are potent inhibitors of integrase activity. Particularly, derivative 8 is a potent IN inhibitor for both steps of the reaction (3'-processing and strand transfer) and exhibits both high antiviral activity against HIV-1 infected cells and low cytotoxicity. Molecular modeling studies provide a plausible mechanism of action, which is consistent with ligand SARs and enzyme photo-cross-linking experiments. C1 Univ Roma La Sapienza, Ist Microbiol, I-00185 Rome, Italy. Ist Super Sanita, Dipartimento Farm, I-00161 Rome, Italy. Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy. NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Ist Pasteur Fdn Cenci Bolognetti, Dipartimento Farmaceut, I-00185 Rome, Italy. RP Di Santo, R (reprint author), Ist Super Sanita, Dipartimento Farmaceut, Rome, Italy. EM roberto.disanto@uniroma1.it; lavecchi@unina.it RI palmisano, lucia/G-5577-2011; Marchand, Christophe/D-8559-2016; andreotti, mauro/K-1436-2016; OI andreotti, mauro/0000-0001-5168-8624; COSTI, Roberta/0000-0002-1314-9029; Di Santo, Roberto/0000-0002-4279-7666; Marinelli, Luciana/0000-0002-4084-8044 FU Intramural NIH HHS [Z01 BC007333-16] NR 33 TC 61 Z9 62 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 23 PY 2006 VL 49 IS 6 BP 1939 EP 1945 DI 10.1021/jm0511583 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 027FQ UT WOS:000236400100013 PM 16539381 ER PT J AU Huang, RL Wallqvist, A Covell, DG AF Huang, RL Wallqvist, A Covell, DG TI Assessment of in vitro and in vivo activities in the National Cancer Institute's anticancer screen with respect to chemical structure, target specificity, and mechanism of action SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DRUG DISCOVERY DATABASES; MITOCHONDRIAL COMPLEX-I; HUMAN LEUKEMIA-CELLS; QSAR; ADAPHOSTIN; MODELS; LINES; INHIBITORS; ALGORITHM; CHEMISTRY AB This paper examines two biological models of anticancer activity, cytotoxicity and hollow fiber (HF) activity, for chemotherapeutic agents evaluated as part of the National Cancer Institute's (NCI's) drug screening effort. Our analysis proposes strategies to globally assess compounds tested in the NCI's 60-cell (NCI60) in vitro anticancer screen in terms of structural features, biological activity, target specificity, and mechanism of action by data integration via our self-organizing maps of structural and biological response patterns. We have built statistical models to predict compound potency and HF activity based on physicochemical properties. Our results find that it is the combination of different structural properties that determines a compound's biological activity. A direct correlation is also found between compound potency and specificity, indicating that specific targeting, rather than promiscuous poisoning, gives rise to potency. Finally, we offer a strategy to exploit this relationship for future mining of novel anticancer candidates. C1 NCI, Dev Therapeut Program, Screening Technol Branch, Lab Compuatat Technol, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Covell, DG (reprint author), NCI, Dev Therapeut Program, Screening Technol Branch, Lab Compuatat Technol, Frederick, MD 21702 USA. EM covell@ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 43 TC 14 Z9 15 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 MAR 23 PY 2006 VL 49 IS 6 BP 1964 EP 1979 DI 10.1021/jm051029m PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 027FQ UT WOS:000236400100016 PM 16539384 ER PT J AU Lee, J Kang, JH Han, KC Kim, Y Kim, SY Youn, HS Mook-Jung, I Kim, H Han, JHL Ha, HJ Kim, YH Marquez, VE Lewin, NE Pearce, LV Lundberg, DJ Blumberg, PM AF Lee, J Kang, JH Han, KC Kim, Y Kim, SY Youn, HS Mook-Jung, I Kim, H Han, JHL Ha, HJ Kim, YH Marquez, VE Lewin, NE Pearce, LV Lundberg, DJ Blumberg, PM TI Branched diacylglycerol-lactones as potent protein kinase C ligands and alpha-secretase activators SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONFORMATIONALLY CONSTRAINED ANALOGS; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; DAG-LACTONES; BINDING-AFFINITY; PK-C; STRATEGIES; CLEAVAGE; BEARING; DESIGN AB Using as our lead structure a potent PKC ligand (1) that we had previously described, we investigated a series of branched DAG-lactones to optimize the scaffold for PKC binding affinity and reduced lipophilicity, and we examined the potential utility of select compounds as alpha-secretase activators. Activation of alpha-secretase upon PKC stimulation by ligands causes increased degradation of the amyloid precursor protein (APP), resulting in enhanced secretion of sAPP alpha and reduced deposition of beta-amyloid peptide (A beta), which is implicated in the pathogenesis of Alzheimer's disease. We modified in a systematic manner the C-5-acyl group, the 3-alkylidene, and the lactone ring in I and established structure-activity relationships for this series of potent PKC ligands. Select DAG-lactones with high binding affinities for PKC were evaluated for their abilities to lead to increased sAPP alpha secretion as a result of alpha-secretase activation. The DAG-lactones potently induced alpha-secretase activation, and their potencies correlated with the corresponding PKC binding affinities and lipophilicities. Further investigation indicated that 2 exhibited a modestly higher level of sAPP alpha secretion than did phorbol 12,13-dibutyrate (PDBu). C1 Seoul Natl Univ, Coll Med, Coll Pharm, Med Chem Lab,Res Inst Pharmaceut Sci,Lab Med Chem, Seoul 151742, South Korea. Seoul Natl Univ, Coll Med, Dept Biochem, Seoul 151742, South Korea. Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 151742, South Korea. Digital Biotec, Ansan 425839, South Korea. NCI, Ctr Canc Res, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Med, Coll Pharm, Med Chem Lab,Res Inst Pharmaceut Sci,Lab Med Chem, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Mook, Inhee/J-2754-2012 FU Intramural NIH HHS NR 27 TC 7 Z9 7 U1 0 U2 1 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 MAR 23 PY 2006 VL 49 IS 6 BP 2028 EP 2036 DI 10.1021/jm0509391 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 027FQ UT WOS:000236400100023 PM 16539391 ER PT J AU Chong, HS Garmestani, K Bryant, LH Milenic, DE Overstreet, T Birch, N Le, T Brady, ED Brechbiel, MW AF Chong, HS Garmestani, K Bryant, LH Milenic, DE Overstreet, T Birch, N Le, T Brady, ED Brechbiel, MW TI Synthesis and evaluation of novel macrocyclic and acyclic ligands as contrast enhancement agents for magnetic resonance imaging SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RADIOIMMUNOTHERAPY; COMPLEXES; LIVER; MRI; KINETICS; RAT AB Novel chelates PIP-DTPA, AZEP-DTPA, NETA, NPTA, and PIP-DOTA were synthesized and evaluated as potential magnetic resonance imaging (MRI) contrast enhancement agents. The T-1 and T-2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the clinically used contrast agents Gd(DTPA) and Gd(DOTA). The serum stability of the Gd-153-labeled complexes, Gd(PIP-DTPA), Gd(AZEP-DTPA), Gd(PIP-DOTA), Gd(NETA), and Gd(NPTA), was assessed by measuring the release of Gd-153 from the complexes. Gd-153(NETA), Gd-153(PIP-DTPA), and Gd-153(PIP-DOTA) were found to be stable in human serum for up to 14 days without any measurable loss of radioactivity. Significant release of Gd-153 was observed with the Gd-153(III) radiolabled NPTA. In vivo biodistribution of the Gd-153-labeled complexes was performed to evaluate their in vivo stability. While Gd(AZEP-DTPA) and Gd(NPTA) were found to be unstable in vivo, Gd(NETA), Gd(PIP-DTPA), and Gd(PIP-DOTA) were excreted without dissociation. These results suggest that the Gd(III) complexes of the novel chelates NETA, PIP-DTPA, and PIP-DOTA possess potential as MRI contrast enhancement agents. In particular, the piperidine backboned chelates Gd(PIP-DTPA) and Gd(PIP-DOTA) displayed reduced kidney retention as compared to the nonspecific MRI contrast agent Gd(DOTA) at all time points, although the observed effects were relatively small at 0.5 h postinjection. Incorporation of the lipophilic piperidine ring appears to confer a moderate effect on the liver uptake of these two chelates. C1 IIT, Biol Chem & Phys Sci Dept, Div Chem, Chicago, IL 60616 USA. NCI, Ctr Canc Res, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. NIH, Diagnost Radiol Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Chong, HS (reprint author), IIT, Biol Chem & Phys Sci Dept, Div Chem, 3101 S Dearborn St,LS 182, Chicago, IL 60616 USA. EM Chong@iit.edu FU Intramural NIH HHS NR 23 TC 25 Z9 29 U1 1 U2 10 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 MAR 23 PY 2006 VL 49 IS 6 BP 2055 EP 2062 DI 10.1021/jm051009k PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 027FQ UT WOS:000236400100026 PM 16539394 ER PT J AU Rush, AJ Trivedi, MH Wisniewski, SR Stewart, JW Nierenberg, AA Thase, ME Ritz, L Biggs, MM Warden, D Luther, JF Shores-Wilson, K Niederehe, G Fava, M AF Rush, AJ Trivedi, MH Wisniewski, SR Stewart, JW Nierenberg, AA Thase, ME Ritz, L Biggs, MM Warden, D Luther, JF Shores-Wilson, K Niederehe, G Fava, M CA STAR D Study Team TI Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAR-ASTERISK-D; SEROTONIN REUPTAKE INHIBITORS; SEQUENCED TREATMENT ALTERNATIVES; RESISTANT MAJOR DEPRESSION; OPEN-LABEL TRIAL; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; TREATMENT STRATEGY; QUICK INVENTORY; RATING SCALE AB BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. METHODS We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram to receive one of the following drugs for up to 14 weeks: sustained-release bupropion (239 patients) at a maximal daily dose of 400 mg, sertraline (238 patients) at a maximal daily dose of 200 mg, or extended-release venlafaxine (250 patients) at a maximal daily dose of 375 mg. The study was conducted in 18 primary and 23 psychiatric care settings. The primary outcome was symptom remission, defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of the study. Scores on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR-16), obtained at treatment visits, determined secondary outcomes, including remission (a score of 5 or less at exit) and response (a reduction of 50 percent or more on baseline scores). RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16, respectively, were 21.3 percent and 25.5 percent for sustained-release bupropion, 17.6 percent and 26.6 percent for sertraline, and 24.8 percent and 25.0 percent for extended-release venlafaxine. QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion, 26.7 percent for sertraline, and 28.2 percent for extended-release venlafaxine. These treatments did not differ significantly with respect to outcomes, tolerability, or adverse events. CONCLUSIONS After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant. Any one of the medications in the study provided a reasonable second-step choice for patients with depression. C1 Univ Texas, SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Coll Phys & Surg, New York, NY USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. NIMH, Bethesda, MD 20892 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 41 TC 521 Z9 530 U1 5 U2 45 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 MAR 23 PY 2006 VL 354 IS 12 BP 1231 EP 1242 DI 10.1056/NEJMoa052963 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 023ZH UT WOS:000236164200002 PM 16554525 ER PT J AU Trivedi, MH Fava, M Wisniewski, SR Thase, ME Quitkin, F Warden, D Ritz, L Nierenberg, AA Lebowitz, BD Biggs, MM Luther, JF Shores-Wilson, K Rush, AJ AF Trivedi, MH Fava, M Wisniewski, SR Thase, ME Quitkin, F Warden, D Ritz, L Nierenberg, AA Lebowitz, BD Biggs, MM Luther, JF Shores-Wilson, K Rush, AJ CA STAR D Study Team TI Medication augmentation after the failure of SSRIs for depression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; ALGORITHM PROJECT; RATIONALE; DISORDER AB BACKGROUND Although clinicians frequently add a second medication to an initial, ineffective antidepressant drug, no randomized controlled trial has compared the efficacy of this approach. METHODS We randomly assigned 565 adult outpatients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy (mean final dose, 55 mg per day) to receive sustained-release bupropion (at a dose of up to 400 mg per day) as augmentation and 286 to receive buspirone (at a dose of up to 60 mg per day) as augmentation. The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression (HRSD-17) at the end of this study; scores were obtained over the telephone by raters blinded to treatment assignment. The 16-item Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR-16) was used to determine the secondary outcomes of remission (defined as a score of less than 6 at the end of this study) and response (a reduction in baseline scores of 50 percent or more). RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission (29.7 percent and 30.1 percent, respectively), QIDS-SR-16 remission (39.0 percent and 32.9 percent), and QIDS-SR-16 response (31.8 percent and 26.9 percent). Sustained-release bupropion, however, was associated with a greater reduction (from baseline to the end of this study) in QIDS-SR-16 scores than was buspirone (25.3 percent vs. 17.1 percent, P<0.04), a lower QIDS-SR-16 score at the end of this study (8.0 vs. 9.1, P<0.02), and a lower dropout rate due to intolerance (12.5 percent vs. 20.6 percent, P<0.009). CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical settings. Augmentation with sustained-release bupropion does have certain advantages, including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Mood Disorder Program & Clin, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. NIMH, Bethesda, MD 20892 USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, Mood Disorder Program & Clin, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM trivedi@utsouthwestern.edu RI Biggs, Dr. Melanie/C-1468-2010; Howland, Robert/K-6937-2015; OI Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 18 TC 517 Z9 527 U1 6 U2 26 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 MAR 23 PY 2006 VL 354 IS 12 BP 1243 EP 1252 DI 10.1056/NEJMoa052964 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 023ZH UT WOS:000236164200003 PM 16554526 ER PT J AU Katuri, V Tang, Y Li, C Jogunoori, W Deng, CX Rashid, A Sidawy, AN Evans, S Reddy, EP Mishra, B Mishra, L AF Katuri, V Tang, Y Li, C Jogunoori, W Deng, CX Rashid, A Sidawy, AN Evans, S Reddy, EP Mishra, B Mishra, L TI Critical interactions between TGF-beta signaling/ELF, and E-cadherin/beta-catenin mediated tumor suppression SO ONCOGENE LA English DT Article DE ELF; Smad4; spectrin; gastrointestinal cancer; E-cadherin ID CELL-CELL ADHESION; GASTRIC-CANCER; MESENCHYMAL TRANSITION; LIVER DEVELOPMENT; IN-VITRO; SPECTRIN; CARCINOMA; MEMBRANE; PROTEIN; MICE AB Inactivation of the transforming growth factor-beta (TGF-beta) pathway occurs often in malignancies of the gastrointestinal (GI) system. However, only a fraction of sporadic GI tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Here, we show a wide range of GI tumors, including those of the stomach, liver and colon in elf(+/-) and elf(+/-)/Smad4(+/-) mutant mice. We found that embryonic liver fodrin ( ELF), a beta-Spectrin originally identified in endodermal stem/progenitor cells committed to foregut lineage, possesses potent antioncogenic activity and is frequently inactivated in GI cancers. Specifically, E-cadherin accumulation at cell-cell contacts and E-cadherin-beta-catenin-dependent epithelial cell-cell adhesion is disrupted in elf(+/-)/Smad4(+)/(-) mutant gastric epithelial cells, and could be rescued by ectopic expression of full-length elf, but not Smad3 or Smad4. Subcellular fractionation revealed that E-cadherin is expressed mainly at the cell membrane after TGF-beta stimulation. In contrast, elf(+/-)/Smad4(+/-) mutant tissues showed abnormal distribution of E-cadherin that could be rescued by overexpression of ELF but not Smad3 or Smad4. Our results identify a group of common lethal malignancies in which inactivation of TGF-beta signaling, which is essential for tumor suppression, is disrupted by inactivation of the ELF adaptor protein. C1 Georgetown Univ, Lab Canc Genet Digest Dis & Dev Mol Biol, Dept Surg, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Dept Surg, Washington, DC USA. Dept Vet Affairs, Washington, DC USA. Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. RP Mishra, B (reprint author), Georgetown Univ, Lab Canc Genet Digest Dis & Dev Mol Biol, Dept Surg, Vincent T Lombardi Canc Res Ctr, Med Dent Bldg NW 210-212,3900 Reservoir Rd,NW, Washington, DC 20007 USA. EM bm72@georgetown.edu; lopamishra@yahoo.com RI Reddy, E. Premkumar/F-6233-2011; deng, chuxia/N-6713-2016 FU NCI NIH HHS [R01 CA106614, R01 CA106614A]; NIDDK NIH HHS [R01 DK056111, R01 DK56111, R01 DK58637] NR 35 TC 27 Z9 27 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 MAR 23 PY 2006 VL 25 IS 13 BP 1871 EP 1886 DI 10.1038/sj.onc.1209211 PG 16 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 024VQ UT WOS:000236224800004 PM 16288220 ER PT J AU Li, M Mizuuchi, M Burke, TR Craigie, R AF Li, M Mizuuchi, M Burke, TR Craigie, R TI Retroviral DNA integration: reaction pathway and critical intermediates SO EMBO JOURNAL LA English DT Article DE integrase; integration; retrovirus; transposition ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN IN-VITRO; HIV-1 INTEGRASE; PREINTEGRATION COMPLEXES; CRYSTAL-STRUCTURE; MU-DNA; CONCERTED INTEGRATION; NUCLEOPROTEIN COMPLEX; CATALYTIC DOMAIN; STRAND TRANSFER AB The key DNA cutting and joining steps of retroviral DNA integration are carried out by the viral integrase protein. Structures of the individual domains of integrase have been determined, but their organization in the active complex with viral DNA is unknown. We show that HIV-1 integrase forms stable synaptic complexes in which a tetramer of integrase is stably associated with a pair of viral DNA ends. The viral DNA is processed within these complexes, which go on to capture the target DNA and integrate the viral DNA ends. The joining of the two viral DNA ends to target DNA occurs sequentially, with a stable intermediate complex in which only one DNA end is joined. The integration product also remains stably associated with integrase and likely requires disassembly before completion of the integration process by cellular enzymes. The results define the series of stable nucleoprotein complexes that mediate retroviral DNA integration. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. RP Craigie, R (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 301,5 Ctr Dr MSC 0560, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU Intramural NIH HHS NR 54 TC 167 Z9 171 U1 0 U2 4 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 MAR 22 PY 2006 VL 25 IS 6 BP 1295 EP 1304 DI 10.1038/sj.emboj.7601005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 031XE UT WOS:000236737700012 PM 16482214 ER PT J AU Koh, KK Quon, MJ Han, SH Chung, WJ Lee, Y Shin, EK AF Koh, KK Quon, MJ Han, SH Chung, WJ Lee, Y Shin, EK TI Anti-inflammatory and metabolic effects of candesartan in hypertensive patients SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 27th Congress of the European-Society-of-Cardiology CY SEP 03-07, 2005 CL Stockholm, SWEDEN SP European Soc Cardiol DE angiotensin II receptor blocker; inflammation; insulin resistance; adiponectin; hypertension ID SMOOTH-MUSCLE-CELLS; VASCULAR ENDOTHELIAL-CELLS; RENIN-ANGIOTENSIN SYSTEM; INSULIN SENSITIVITY; CD40 LIGAND; ADIPONECTIN; MACROPHAGES; BLOCKADE; PROTEIN; RISK AB Background: Angiotensin II type 1 (ATI) receptor blocker therapy prevented or retarded the progression of coronary heart disease. The mechanisms of this benefit may relate to the ability of ATI receptor blockers to reduce inflammation and insulin resistance. Methods: We administered placebo or candesartan 16 mg daily during 2 months to 45 patients with mild to moderate hypertension. This study was randomized, double-blind, placebo-controlled, crossover in design. Results: Candesartan therapy significantly lowered both systolic and diastolic blood pressure. Compared with placebo, candesartan therapy significantly lowered plasma hsCRP levels relative to baseline measurements from 1.10 to 0.70 mg/l (P=0.024) and soluble CD40 ligand levels by 30 +/- 11% (P < 0.001). There were significant inverse correlations between body mass index and baseline plasma adiponectin levels (r = -0.480, P = 0.009). There were significant correlations between baseline adiponectin levels and baseline insulin (r = -0.317, P = 0.034) or baseline Quantitative Insulin-Sensitivity Check Index (QUICKI), a surrogate index of insulin sensitivity (r = 0.371, P = 0.012). Compared with placebo, candesartan therapy significantly lowered fasting insulin levels (P = 0.011) and increased plasma levels of adiponectin by 15 +/- 4% (P = 0.012) and increased QUICKI by 8 +/- 2% (P = 0.007). There were significant correlations between percent changes in adiponectin levels and percent changes in insulin (r = -0.340, P = 0.022) or QUICKI (r = 0.325, P = 0.029). Conclusions: Candesartan therapy significantly reduced inflammation and increased adiponectin levels and improved insulin sensitivity in hypertensive patients. (c) 1 2005 Elsevier Ireland Ltd. All rights reserved. C1 Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit Cardiol, Inchon 405760, South Korea. NCCAM, Clin Invest Lab, Diabet Unit, NIH, Bethesda, MD USA. Ewha Womans Univ, Dept Stat, Seoul 120750, South Korea. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit Cardiol, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Chung, Wook-Jin/0000-0002-9767-7098; Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 32 TC 64 Z9 68 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 22 PY 2006 VL 108 IS 1 BP 96 EP 100 DI 10.1016/j.ijcard.2005.07.040 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 028GN UT WOS:000236475100016 PM 16246439 ER PT J AU Van, PL Bakalov, VK Zinn, AR Bondy, CA AF Van, PL Bakalov, VK Zinn, AR Bondy, CA TI Maternal X chromosome, visceral adiposity, and lipid profile SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Sch, McDermott Ctr Human Growth & Dev, Dallas, TX 75230 USA. RP Van, PL (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [NS35554] NR 7 TC 21 Z9 22 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 22 PY 2006 VL 295 IS 12 BP 1373 EP 1374 DI 10.1001/jama.295.12.1373 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 023WU UT WOS:000236157700012 PM 16551706 ER PT J AU Schmidt, PJ Cardoso, GMP Ross, JL Haq, N Bondy, CA AF Schmidt, PJ Cardoso, GMP Ross, JL Haq, N Bondy, CA TI Shyness, social anxiety, and impaired self-esteem in Turner syndrome and premature ovarian failure SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PHOBIA C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Schmidt, PJ (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM peterschmidt@mail.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [NS42777] NR 8 TC 50 Z9 51 U1 0 U2 5 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 MAR 22 PY 2006 VL 295 IS 12 BP 1374 EP 1376 DI 10.1001/jama.295.12.1374 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 023WU UT WOS:000236157700013 PM 16551707 ER PT J AU Yaro, AS Dao, A Adamou, A Crawford, JE Ribeiro, JMC Gwadz, R Traore, SF Lehmann, T AF Yaro, AS Dao, A Adamou, A Crawford, JE Ribeiro, JMC Gwadz, R Traore, SF Lehmann, T TI The distribution of hatching time in Anopheles gambiae SO MALARIA JOURNAL LA English DT Article ID WESTERN KENYA; INCIPIENT SPECIATION; POPULATION-STRUCTURE; LARVAL DEVELOPMENT; MOLECULAR-FORMS; AEDES-AEGYPTI; CULICIDAE; DIPTERA; FUNESTUS; SENEGAL AB Background: Knowledge of the ecological differences between the molecular forms of Anopheles gambiae and their sibling species, An. arabiensis might lead to understanding their unique contribution to disease transmission and to better vector control as well as to understanding the evolutionary forces that have separated them. Methods: The distributions of hatching time of eggs of wild An. gambiae and An. arabiensis females were compared in different water types. Early and late hatchers of the S molecular form were compared with respect to their total protein content, sex ratio, development success, developmental time and adult body size. Results: Overall, the distribution of hatching time was strongly skewed to the right, with 89% of the eggs hatching during the second and third day post oviposition, 10% hatching during the next four days and the remaining 1% hatching over the subsequent week. Slight, but significant differences were found between species and between the molecular forms in all water types. Differences in hatching time distribution were also found among water types ( in each species and molecular form), suggesting that the eggs change their hatching time in response to chemical factors in the water. Early hatchers were similar to late hatchers except that they developed faster and produced smaller adults than late hatchers. Conclusion: Differences in hatching time and speed of development among eggs of the same batch may be adaptive if catastrophic events such as larval site desiccation are not rare and the site's quality is unpredictable. The egg is not passive and its hatching time depends on water factors. Differences in hatching time between species and molecular forms were slight, probably reflecting that conditions in their larval sites are rather similar. C1 NIAID, Lab Maleria & Vector Res, NIH, Rockville, MD 20852 USA. Malaria Res & Training Ctr, Bamako, Mali. RP Lehmann, T (reprint author), NIAID, Lab Maleria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM yaro@mrtcbko.org; adama@mrtcbko.org; adamou@mrtcbko.org; crawfordj@niaid.nih.gov; jribeiro@niaid.nih.gov; rgwadz@niaid.nih.gov; cheick@mrtcbko.org; tlehmann@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS NR 35 TC 26 Z9 26 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAR 22 PY 2006 VL 5 AR 19 DI 10.1186/1475-2875-5-19 PG 7 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 052XX UT WOS:000238268500001 PM 16553960 ER PT J AU Lewis, W Kohler, JJ Hosseini, SH Haase, CP Copeland, WC Bienstock, RJ Ludaway, T McNaught, J Russ, R Stuart, T Santoianni, R AF Lewis, W Kohler, JJ Hosseini, SH Haase, CP Copeland, WC Bienstock, RJ Ludaway, T McNaught, J Russ, R Stuart, T Santoianni, R TI Antiretroviral nucleosides, deoxynucleotide carrier and mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis SO AIDS LA English DT Article DE mitochondria; deoxynucleotide carrier; nucleoside reverse transcriptase inhibitor; DNA polymerase; AIDS; transgenic; cardiomyopathy; heart ID REVERSE-TRANSCRIPTASE INHIBITORS; THERAPY-RELATED LIPODYSTROPHY; POLYMERASE-GAMMA; TRANSGENIC EXPRESSION; CAUSES CARDIOMYOPATHY; MUSCLE MITOCHONDRIA; ANTIVIRAL ACTIVITY; OXIDATIVE STRESS; TOXICITY; ZIDOVUDINE AB Design: Nucleoside reverse transcriptase inhibitors (NRTIs) exhibit mitochondrial toxicity. The mitochondrial deoxynucleotide carrier (DNC) transports nucleotide precursors (or phosphorylated NRTIs) into mitochondria for mitochondrial (mt)DNA replication or inhibition of mtDNA replication by NRTIs. Transgenic mice (TG) expressing human DNC targeted to murine myocardium served to define mitochondrial events from NRTIs in vivo and findings were corroborated by biochemical events in vitro. Methods: Zidovudine (3-azido-2',3'-deoxythymidine; ZDV), stavudine (2', 3'-didehydro-2', 3'-deoxythymidine; d4T), or lamivudine ((-)-2-deoxy-3'-thiacytidine; 3TC) were administered individually to TGs and wild-type (WT) littermates (35 days) at human doses with drug-free vehicle as control. Left ventricle (LV) mass was defined echocardiographically, mitochondrial ultrastructural defects were identified by electron microscopy, the abundance of cardiac mtDNA was quantified by real time polymerase chain reaction, and mtDNA-encoded polypeptides were quantified. Results: Untreated TGs exhibited normal LV mass with minor mitochondrial damage. NRTI monotherapy (either d4T or ZDV) increased LV mass in TGs and caused significant mitochondrial destruction. Cardiac mtDNA was depleted in ZDV and d4T-treated TG hearts and mtDNA-encoded polypeptides decreased. Changes were absent in 3TC-treated cohorts. In supportive structural observations from molecular modeling, ZDV demonstrated close contacts with K947 and Y951 in the DNA pol gamma active site that were absent in the HIV reverse transcriptase active site. Conclusions: NRTIs deplete mtDNA and polypeptides, cause mitochondrial structural and functional defects in vivo, follow inhibition kinetics with DNA pol gamma in vitro, and are corroborated by molecular models. Disrupted pools of nucleotide precursors and inhibition of DNA pol gamma by specific NRTIs are mechanistically important in mitochondrial toxicity. (C) 2006 Lippincott Williams & Wilkins. C1 Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Lewis, W (reprint author), Emory Univ, Sch Med, Dept Pathol, 7117 Woodruff Mem Bldg,101 Woodruff Circle, Atlanta, GA 30322 USA. EM wlewis@emory.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL059798, R01 HL063666, R01 HL072707] NR 55 TC 83 Z9 91 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 21 PY 2006 VL 20 IS 5 BP 675 EP 684 DI 10.1097/01.aids.0000216367.23325.58 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 027MZ UT WOS:000236421000006 PM 16514297 ER PT J AU Palmer, S Boltz, V Maldarelli, F Kearney, M Halvas, EK Rock, D Falloon, J Davey, RT Dewar, RL Metcalf, JA Mellors, JW Coffin, JM AF Palmer, S Boltz, V Maldarelli, F Kearney, M Halvas, EK Rock, D Falloon, J Davey, RT Dewar, RL Metcalf, JA Mellors, JW Coffin, JM TI Selection and persistence of non-nucleoside reverse transcriptase inhibitor-resistant HIV-1 in patients starting and stopping non-nucleoside therapy SO AIDS LA English DT Article DE HIV resistance; non-nucleoside reverse transcriptase inhibitor; allele-specific polymerase chain reaction; NNRTI resistance; persistence of NNRTI resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; SINGLE-DOSE NEVIRAPINE; LONG-TERM PERSISTENCE; DRUG-RESISTANCE; IN-VIVO; ANTIRETROVIRAL THERAPY; TREATMENT INTERRUPTION; GENOTYPIC RESISTANCE; TYPE-1 POPULATIONS AB Background: Understanding the selection and decay of drug-resistant HIV-1 variants is important for designing optimal antiretroviral therapy. Objective: To develop a high-throughput, real-time reverse transcriptase (RT) polymerase chain reaction (PCR) assay to quantify non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant variants K103N (AAT or AAC alleles) at frequencies as low as 0.1%, and to apply this to monitor these variants before, during, and after NNRTI therapy. Methods: HIV-1 RNA in longitudinal plasma samples obtained from patients starting and stopping NNRTI therapy was converted to cDNA and the target sequence region amplified and quantified by real-time PCR. Approximately 10(7) copies/reaction provided a template for a second round of PCR using primers that discriminated between the mutant and wild-type alleles. Amplification specificity was confirmed by thermal denaturation analysis. Results: Frequencies of 103N similar to assay background (0.029%) were observed in longitudinal samples from 9 of 12 treatment-naive patients; three patients had transient increases in 103N frequency to a range of 0.21-0.48%, which was 7-16.5 times assay background. Analysis of longitudinal plasma samples from six NNRTI-experienced patients showed three patterns: persistence of 103N variants after stopping NNRTI therapy, codon switching of 103N between AAC and AAT during NNRTI therapy, and decay of 103N variants to below assay background after cessation of NNRTI therapy. Conclusions: Allele-specific RT-PCR quantified the emergence and decay of drug-resistant variants in patients over a broad range of frequencies (0.1-100%). The rate of decay of K103N variants after stopping NNRTI therapy was highly variable. (C) 2006 Lippincott Williams & Wilkins. C1 NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. SAIC, Frederick, MD USA. Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, CCMD Clin, NIH, Bethesda, MD 20892 USA. RP Palmer, S (reprint author), NCI, HIV Drug Resistance Program, NIH, 1050 Boyles St,Bldg 535,Room 109, Frederick, MD 21702 USA. EM spalmer@ncifcrf.gov FU NIAID NIH HHS [U01AI38858] NR 46 TC 76 Z9 80 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 21 PY 2006 VL 20 IS 5 BP 701 EP 710 DI 10.1097/01.aids.0000216370.69066.7f PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 027MZ UT WOS:000236421000009 PM 16514300 ER PT J AU Aberg, JA Rosenkranz, SL Fichtenbaum, CJ Alston, BL Brobst, SW Segal, Y Gerber, JG AF Aberg, JA Rosenkranz, SL Fichtenbaum, CJ Alston, BL Brobst, SW Segal, Y Gerber, JG CA ACTG A5108 Team TI Pharmacokinetic interaction between nelfinavir and pravastatin in HIV-seronegative volunteers: ACTG study A5108 SO AIDS LA English DT Article; Proceedings Paper CT 2nd International-AIDS-Society Conference on HIV Pathogenesis and Treatment CY JUL 13-16, 2003 CL Paris, FRANCE SP Int AIDS Soc DE HIV infection; statins; pravastatin; nelfinavir; drug interactions ID A REDUCTASE INHIBITORS; LIPID-LOWERING THERAPY; CLINICAL-TRIALS GROUP; ANTIRETROVIRAL THERAPY; TRANSPLANT RECIPIENTS; ATORVASTATIN; DYSLIPIDEMIA; SIMVASTATIN; MANAGEMENT; INFECTION AB Background: Nelfinavir, an HIV protease inhibitor with numerous drug-drug interactions, is associated with dyslipidemia. Pravastatin is the preferred statin prescribed for HIV-associated dyslipidemia. Objective: To examine the effect of nelfinavir on pravastatin pharmacokinetics. Design: Open-label study in healthy HIV-seronegative adults conducted at the AIDS Clinical Trials Group sites in the United States. Methods: Subjects received pravastatin 40 mg daily and underwent intensive sampling for pharmacokinetics on day 3. Subjects took only nelfinavir 1250 mg twice daily on days 4-12. On days 13-15, subjects continued nelfinavir and reinitiated pravastatin. Plasma samples were collected over 24 h for the calculation of pravastatin area under the concentration-time curve for 0-24 h on days 3 and 16. Results: Data from 14 subjects with complete pharmacokinetic samples were available for analysis. The median within-subject percentage change in pravastatin AUC was a decrease of 46.5%. Pravastatin maximum plasma concentrations were also lower when pravastatin was administered with nelfinavir. Median values for the maximum plasma concentrations were 27.9 and 12.4 ng/ml for days 3 and 16, respectively, and the median within-subject decrease was 40.1%. Conclusions: Coadministration of pravastatin and nelfinavir led to a substantial reduction in pravastatin plasma concentrations. Higher doses of pravastatin may need to be prescribed in order to achieve optimal lipid-lowering activity. (C) 2006 Lippincott Williams & Wilkins. C1 NYU, New York, NY 10016 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Social & Sci Syst Inc, Silver Spring, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Aberg, JA (reprint author), NYU, 550 1st Ave,room 558,Bellevue C&D Bldg, New York, NY 10016 USA. EM judith.aberg@med.nyu.edu FU NCRR NIH HHS [M01-RR00070, M01 RR000070, M01 RR000044]; NIAID NIH HHS [U01 AI027658, AI-38858, AI-38855, U01 AI032770, U01 AI025897, U01 AI027665, AI -27665, AI-27666, U01 AI038858, U01 AI038855, AI-25897, U01 AI027666, AI-32770, AI-27658] NR 20 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 21 PY 2006 VL 20 IS 5 BP 725 EP 729 DI 10.1097/01.aids.0000216373.53819.92 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 027MZ UT WOS:000236421000012 PM 16514303 ER PT J AU Koblin, BA Husnik, MJ Colfax, G Huang, YJ Madison, M Mayer, K Barresi, PJ Coates, TJ Chesney, MA Buchbinder, S AF Koblin, BA Husnik, MJ Colfax, G Huang, YJ Madison, M Mayer, K Barresi, PJ Coates, TJ Chesney, MA Buchbinder, S TI Risk factors for HIV infection among men who have sex with men SO AIDS LA English DT Article DE alcohol use; depression; HIV; men who have sex with men; sexually transmitted diseases; substance use ID SEXUALLY-TRANSMITTED-DISEASES; NEW-YORK-CITY; IMMUNODEFICIENCY-VIRUS SEROCONVERSION; LONGITUDINAL DATA-ANALYSIS; MULTICENTER AIDS COHORT; INJECTION-DRUG-USERS; BASE-LINE DATA; HOMOSEXUAL-MEN; BISEXUAL MEN; SAN-FRANCISCO AB Objectives: Risk factors for HIV acquisition were examined in a recent cohort of men who have sex with men (MSM). Design: A longitudinal analysis of 4295 HIV-negative MSM enrolled in a randomized behavioral intervention trial conducted in six US cities. Methods: MSM were enrolled and assessed for HIV infection and risk behaviors semiannually, up to 48 months. Results: In multivariate analysis, men reporting four or more male sex partners, unprotected receptive anal intercourse with an), HIV serostatus partners and unprotected insertive anal intercourse with HIV-positive partners were at increased risk of HIV infection, as were those reporting amphetamine or heavy alcohol use and alcohol or drug use before sex. Some depression symptoms and occurrence of gonorrhea also were independently associated with HIV infection. The attributable fractions of high number of male partners, use of alcohol or drugs before sex, and unprotected receptive anal intercourse with unknown status partners and the same with presumed negative partners accounted for 32.3, 29.0, 28.4 and 21.6% of infections, respectively. Conclusions: The challenge is to develop strategies to identify men in need. Interventions are needed to help men reduce their number of sexual partners, occurrences of unprotected anal intercourse, alcohol or drug use before sex and address other mental health issues. (C) 2006 Lippincott Williams & Wilkins. C1 New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA. NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Fenway Community Hlth Ctr, Boston, MA USA. ABT Associates Inc, Cambridge, MA 02138 USA. Emory Univ, Atlanta, GA 30322 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. RP Koblin, BA (reprint author), New York Blood Ctr, Lab Infect Dis Prevent, 310 E 67th St, New York, NY 10021 USA. EM bkoblin@nybloodcenter.org FU NIAID NIH HHS [N01 AI35176, 5 U01 AI46749, N01 AI45200, U01 AI47981, U01 AI47995, U01 AI48016, U01 AI48040] NR 62 TC 358 Z9 373 U1 6 U2 37 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 21 PY 2006 VL 20 IS 5 BP 731 EP 739 DI 10.1097/01.aids.0000216374.61442.55 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 027MZ UT WOS:000236421000013 PM 16514304 ER PT J AU Xie, ZH Yuan, HY Yin, YZ Zeng, X Bai, RK Glazer, RI AF Xie, ZH Yuan, HY Yin, YZ Zeng, X Bai, RK Glazer, RI TI 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) promotes invasion and activation of matrix metalloproteinases SO BMC CANCER LA English DT Article ID MAMMARY EPITHELIAL-CELLS; BREAST-CANCER CELLS; GENE-EXPRESSION; MICROARRAY ANALYSIS; CDNA MICROARRAY; TUMOR INVASION; MEMBRANE; METASTASIS; GROWTH; SERUM AB Background: Metastasis is a major cause of morbidity and mortality in breast cancer with tumor cell invasion playing a crucial role in the metastatic process. PDK1 is a key molecule that couples PI3K to cell proliferation and survival signals in response to growth factor receptor activation, and is oncogenic when expressed in mouse mammary epithelial cells. We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. These properties correlate with induction of MMP-2 activity, increased MT1-MMP expression and a unique gene expression profile. Methods: Invasion assays in Matrigel, MMP-2 zymogram analysis, gene microarray analysis and mammary isografts were used to characterize the invasive and proliferative function of cells expressing PDK1. Tissue microarray analysis of human breast cancers was used to measure PDK1 expression in invasive tumors by IHC. Results: Enhanced invasion on Matrigel in PDK1-expressing cells was accompanied by increased MMP-2 activity resulting from stabilization against proteasomal degradation. Increased MMP-2 activity was accompanied by elevated levels of MT1-MMP, which is involved in generating active MMP-2. Gene microarray analysis identified increased expression of the ECM-associated genes decorin and type I procollagen, whose gene products are substrates of MT1-MMP. Mammary fat pad isografts of PDK1-expressing cells produced invasive adenocarcinomas. Tissue microarray analysis of human invasive breast cancer indicated that PDK1pSer241 was strongly expressed in 90% of samples. Conclusion: These results indicate that PDK1 serves as an important effector of mammary epithelial cell growth and invasion in the transformed phenotype. PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. The presence of increased PDK1 expression in the majority of invasive breast cancers suggests its importance in the metastatic process. C1 Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20057 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. NIAID, Lab Allerg Dis, Rockville, MD USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Glazer, RI (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Washington, DC 20057 USA. EM xiez@niaid.nih.gov; hy38@georgetown.edu; yiny@georgetown.edu; xzeng@superarray.net; bai@bcm.tmc.edu; glazerr@georgetown.edu FU NCI NIH HHS [R01CA81565] NR 48 TC 33 Z9 35 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 21 PY 2006 VL 6 AR 77 DI 10.1186/1471-2407-6-77 PG 12 WC Oncology SC Oncology GA 042ZU UT WOS:000237569900001 PM 16551362 ER PT J AU Li, XM Cui, XZ Li, Y Fitz, Y Hsu, L Eichacker, PQ AF Li, XM Cui, XZ Li, Y Fitz, Y Hsu, L Eichacker, PQ TI Parthenolide has limited effects on nuclear factor-kappa beta increases and worsens survival in lipopolysaccharide-challenged C57BL/6J mice SO CYTOKINE LA English DT Article DE anti-inflammatory agent; lipopolysaccharide; treatment; signaling molecules ID NITRIC-OXIDE SYNTHASE; SESQUITERPENE LACTONES; GENE-EXPRESSION; SEPTIC SHOCK; B ACTIVATION; POTENT INHIBITORS; ENDOTOXIC-SHOCK; IN-VIVO; CELLS; PATHWAY AB Parthenolide, a sesquiterpene lactone, inhibited lipopolysaccharide (LPS) stimulated nuclear factor (NF)-kappa B and cytokine production in vitro and in rats, and improved survival in LPS challenged Swiss albino mice. We investigated whether increased survival with parthenolide was associated directly with inhibition of NF-kappa B and cytokines in LPS challenged C57BL/6J mice. In RAW 264.7 cells, parthenolide inhibited LPS-stimulated NF-kappa B and cytokines (interleukin [IL]-1 alpha, -1 beta, -2, -4, -6, and -10, interferon-gamma, tumor necrosis factor-alpha, granulocyte macrophage-colony stimulating factor, migratory inhibitory protein-1 and -2 alpha, JE, and RANTES). In mice (n = 366) receiving lethal intraperitoneal (i.p.) LPS (40 mg/kg), compared to placebo, each of 5 parthenolide doses (0.25 to 4 mg/kg i.p. following LPS) reduced survival at 168 h and overall worsened the hazards ratio of survival (mean +/- S.E.M.) (1.29 +/- 0.12, p = 0.04). In other mice (241), compared to saline challenge, nonlethal LPS (2.5 mg/kg) increased NF-kappa B in lung and kidney combined and 12 of 13 plasma cytokines early (1 and 3 h) and late (6, 9 and 12 h) (p <= 0.002 for each). Compared to nonlethal LPS, lethal LPS increased NF-kappa B and 12 of 13 cytokines early but not significantly and late significantly (p <= 0.05 for each). With lethal LPS, compared to placebo, parthenolide (1 mg/kg) decreased NF-kappa B and 10 of 13 cytokines early and increased NF-kappa B and 11 of 13 cytokines late (p <= 0.02 for early vs. late). Although parthenolide inhibits NF-kappa B and cytokines in vitro, its effects on these mediators and survival in animal sepsis models vary. Theses differences must be understood before parthenolide or related agents are applied clinically for sepsis. (c) 2006 Published by Elsevier Ltd. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. EM peichacker@cc.nih.gov NR 36 TC 13 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR 21 PY 2006 VL 33 IS 6 BP 299 EP 308 DI 10.1016/j.cyto.2006.03.002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 055QG UT WOS:000238464800001 PM 16720096 ER PT J AU Kondrashov, FA Kondrashov, AS AF Kondrashov, FA Kondrashov, AS TI Role of selection in fixation of gene duplications SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Review DE selection; duplication; fixation; evolution ID MOSQUITO CULEX-PIPIENS; COMPARATIVE GENOMIC HYBRIDIZATION; PELIZAEUS-MERZBACHER-DISEASE; FAMILIAL PARKINSONS-DISEASE; ADAPTIVE PROTEIN EVOLUTION; MULTIDRUG-RESISTANCE GENE; COPY-NUMBER; SEGMENTAL DUPLICATIONS; INSECTICIDE RESISTANCE; ALPHA-SYNUCLEIN AB New genes commonly appear through complete or partial duplications of pre-existing genes. Duplications of long DNA segments arc constantly produced by rare Mutations, may become fixed in a population by selection or random drift, and are subject to divergent evolution of the paralogous sequences after fixation. although gene conversion call impede this process. New data shed sonic light oil each of these processes. Mutations which involve duplications can occur through at least two different mechanisms, backward Wand slippage during DNA replication and unequal crossing-over. The background rate of duplication of a complete gene ill humans is 10(-9)-10(-10) per generation, although many genes located within hot-spots of large-scale mutation are duplicated much more often. Many gene duplications affect fitness strongly, and tire responsible, through gene dosage effects. for it number of genetic diseases. However. high levels of intrapopulation polymorphism caused by presence or absence of long, gene-containing DNA segments imply that sonic duplications are not under strong selection. The polymorphism to fixation ratios appear to be approximately the same for gene duplications and for presumably selectively neutral nucleotide substitutions, which, according to the McDonald-Kreitman test, is consistent with selective neutrality of duplications. However, this pattern can also be due to negative selection against most of segregating duplications and positive selection for at least some duplications which become fixed. Patterns in post-fixation evolution of duplicated genes do not easily reveal the causes of fixations. Many gene duplications which became fixed recently in a variety of organisms were positively selected because the increased expression of the corresponding genes was beneficial. The effects of gene dosage provide a unified framework for studying all phases of the life history of a gene duplication. Application of well-known methods or evolutionary genetics to accumulating data on new, polymorphic, and fixed duplication will enhance our understanding of the role of natural selection in the evolution by gene duplication. (C) 2005 Elsevier Ltd. All rights reserved. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Rybka Res Inst, Gaithersburg, MD 20882 USA. RP Kondrashov, AS (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM kondrashov@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 148 TC 109 Z9 110 U1 4 U2 43 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD MAR 21 PY 2006 VL 239 IS 2 BP 141 EP 151 DI 10.1016/j.jtbi.2005.08.033 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 026LP UT WOS:000236340700003 PM 16242725 ER PT J AU Badano, A Sempau, J AF Badano, A Sempau, J TI MANTIS: combined x-ray, electron and optical Monte Carlo simulations of indirect radiation imaging systems SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID POINT-SPREAD FUNCTION; CODE PENELOPE; COLUMNAR PHOSPHORS; LEKSELL-GAMMA-KNIFE(R); SCINTILLATORS; COLLECTION; EFFICIENCY; TRANSPORT; SCREENS; BEAMS AB We describe MANTIS (Monte carlo x-rAy electroN opTical Imaging Simulation), a tool for simulating imaging systems that tracks x-rays, electrons and optical photons in arbitrary materials and complex geometries. The x-ray and electron transport and involved physics models are from the PENELOPE package, and the optical transport and corresponding physics models are from DETECT-II and include Fresnel refraction and reflection at material boundaries, bulk absorption and scattering. Complex geometries can be handled with the aid of the geometry routines included in PENELOPE. When x-rays or electrons interact and deposit energy in the scintillator, the code generates a number of optical quanta according to a user-selected model for the conversion process. The optical photons are then tracked until they reach an absorption event, which in some cases contributes to the output signal, or escape from the geometry. We demonstrate the capabilities of this new tool with respect to the statistics of the optical signal detected and to the three-dimensional point-response functions corresponding to columnar phosphor screens. C1 NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. Univ Politecn Catalunya, Inst Tecn Energet, E-08028 Barcelona, Spain. RP Badano, A (reprint author), NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy,HFZ-142, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov; josep.sempau@upc.es RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 37 TC 51 Z9 51 U1 0 U2 9 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2006 VL 51 IS 6 BP 1545 EP 1561 DI 10.1088/0031-9155/51/6/013 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 034QA UT WOS:000236944500013 PM 16510962 ER PT J AU Stan, G Brooks, BR Lorimer, GH Thirumalai, D AF Stan, G Brooks, BR Lorimer, GH Thirumalai, D TI Residues in substrate proteins that interact witn GroEL in tne capture process are buried in the native state SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chaperonin; E. coli; natural substrates; recognition motif ID CHAPERONIN GROEL; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ANNEALING MECHANISM; MOLECULAR-DYNAMICS; POLYPEPTIDE; COMPLEX; BINDING; SURFACE AB We have used a bioinformatic approach to predict the natural substrate proteins for the Escherichia coli chaperonin GroEL based on two simple criteria. Natural substrate proteins should contain binding motifs similar in sequence to the mobile loop peptide of GroES that displaces the binding motif during the chaperonin cycle. Secondly, each substrate protein should contain multiple copies of the binding motif so that the chaperonin can perform "work" on the substrate protein. To validate these criteria, we have used a database of 252 proteins that have been experimentally shown to interact with the chaperonin machinery in vivo. More than 80% are identified by these criteria. The binding motifs of all 79 proteins in the database with a known three-dimensional structure are buried (< 50% solvent-accessible surface area) in the native state. Our results show that the binding motifs are inaccessible in the native state but become solvent-exposed in unfolded state, thus enabling GroEL to distinguish between unfolded and native states. The structures of the binding motif in the native states of the substrate proteins include alpha-helices, beta-strands, and random coils. The diversity of secondary structures implies that there are large and varied conformational transitions in the recognition motifs after their displacement by the mobile loops of GroES. C1 Univ Maryland, Biophys Program, Inst Phys Sci & Technol, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Lorimer, GH (reprint author), Univ Maryland, Biophys Program, Inst Phys Sci & Technol, College Pk, MD 20742 USA. EM glorimer@umd.edu; thirum@glue.umd.edu FU Intramural NIH HHS; NIGMS NIH HHS [1R01 GM 067851-01, R01 GM067851] NR 30 TC 26 Z9 26 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 21 PY 2006 VL 103 IS 12 BP 4433 EP 4438 DI 10.1073/pnas.0600433103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 026SN UT WOS:000236362600022 PM 16537402 ER PT J AU Nakai, K Kadiiska, MB Jiang, JJ Stadler, K Mason, RP AF Nakai, K Kadiiska, MB Jiang, JJ Stadler, K Mason, RP TI Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lipopolysaccharide; mouse skin ID INDUCED OXIDATIVE STRESS; ULTRAVIOLET-B RADIATION; TOLL-LIKE RECEPTORS; FACTOR-KAPPA-B; HUMAN KERATINOCYTES; NADPH OXIDASE; TUMOR PROMOTION; INNATE IMMUNITY; CARBON-DIOXIDE; MURINE SKIN AB Free radical formation has been investigated in diverse experimental models of LPS-induced inflammation. Here, using electron spin resonance (ESR) and the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, we have detected an ESR spectrum of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical adducts in the lipid extract of mouse skin treated with LPS for 6 h. The ESR spectrum was consistent with the trapping of lipid-derived radical adducts. In addition, a secondary radical-trapping technique using dimethyl sulfoxide (DMSO) demonstrated methyl radical formation, revealing the production of hydroxyl radical. Radical adduct formation was suppressed by aminoguanidine, N-(3-aminomethyl)benzylacetamidine (1400W), or allopurinol, suggesting a role for both inducible nitric oxide synthase (iNOS) and xanthine oxidase (XO) in free radical formation. The radical formation was also suppressed in iNOS knockout (iNOS(-/-)) mice, demonstrating the involvement of iNOS. NADPH oxidase was not required in the formation of these radical adducts because the ESR signal intensity was increased by LPS treatment in NADPH oxidase knockout (gp91(phox-/-)) mice as much as it was in the wild-type mouse. Nitric oxide ((NO)-N-center dot) end products were increased in LPS-treated skin. As expected, the (NO)-N-center dot end products were not suppressed by allopurinol but were by aminoguanidine. Interestingly, nitrotyrosine formation in LPS-treated skin was also suppressed by aminoguanidine and allopurinol independently. Pretreatment with the ferric iron chelator Desferal had no effect on free radical formation. Our results imply that both iNOS and XO, but neither NADPH oxidase nor ferric iron, work synergistically to form lipid radical and nitrotyrosine early in the skin inflammation caused by LPS. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F0-01, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov NR 43 TC 43 Z9 44 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 21 PY 2006 VL 103 IS 12 BP 4616 EP 4621 DI 10.1073/pnas.0510352103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 026SN UT WOS:000236362600053 PM 16537416 ER PT J AU Yoder, K Sarasin, A Kraemer, K McIlhatton, M Bushman, F Fishel, R AF Yoder, K Sarasin, A Kraemer, K McIlhatton, M Bushman, F Fishel, R TI The DNA repair genes XPB and XPD defend cells from retroviral infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; ERCC2; ERCC3; HIV; xeroderma pigmentosum ID NUCLEOTIDE EXCISION-REPAIR; XERODERMA-PIGMENTOSUM; SACCHAROMYCES-CEREVISIAE; TY1 RETROTRANSPOSITION; COCKAYNE-SYNDROME; IN-VIVO; VIRUS; TRICHOTHIODYSTROPHY; TRANSCRIPTION; INTEGRATION AB Reverse transcription of retroviral RNA genomes produce a double-stranded linear cDNA molecule. A host degradation system prevents a majority of the cDNA molecules from completing the obligatory genomic integration necessary for pathogenesis. We demonstrate that the human TFIIH complex proteins XPB (ERCC3) and XPD (ERCC2) play a principal role in the degradation of retroviral cDNA. DNA repair-deficient XPB and XPD mutant cell lines exhibited an increase in transduction efficiency by both HIV-and Moloney murine leukemia virus-based retroviral vectors. Replicating Moloney murine leukemia virus viral production was greater in XPB or XPD mutant cells but not XPA mutant cells. Quantitative PCR showed an increase in total cDNA molecules, integrated provirus, and 2LTR circles in XPB and XPD mutant cells. in the presence of a reverse transcription inhibitor, the HIV cDNA appeared more stable in mutant XPB or XPD cells. These studies implicate the nuclear DNA repair proteins XPB and XPD in a cellular defense against retroviral infection. C1 Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. Inst Gustave Roussy, CNRS, F-94805 Villejuif, France. NCI, Basic Res Lab, Bethesda, MD 20892 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. RP Fishel, R (reprint author), Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. EM rfishel@osu.edu OI Yoder, Kristine/0000-0002-5598-9018 FU NCI NIH HHS [CA 56542, R01 CA056542]; NIDDK NIH HHS [T32 DK 07705, T32 DK007705] NR 45 TC 37 Z9 39 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 21 PY 2006 VL 103 IS 12 BP 4622 EP 4627 DI 10.1073/pnas.0509828103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 026SN UT WOS:000236362600054 PM 16537383 ER PT J AU Deleu, S Choi, K Reece, JM Shears, SB AF Deleu, S Choi, K Reece, JM Shears, SB TI Pathogenicity of Salmonella: SopE-mediated membrane ruffling is independent of inositol phosphate signals SO FEBS LETTERS LA English DT Article DE SopE; InsP5; inositolphosphate; cytoskeleton; membrane ruffling; Salmonella ID PLECKSTRIN HOMOLOGY DOMAINS; MESSENGER-RNA EXPORT; ACTIN CYTOSKELETON; PHOSPHOINOSITIDE METABOLISM; EPITHELIAL-CELLS; TUMOR-SUPPRESSOR; HOST-CELL; PTEN; PROTEIN; ACTIVATION AB Studies [Zhou, D., Chen, L.-M., Hernandez, L., Shears, S.B., and Galin, J.E. (2001) A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host-cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol. 39, 248-259] with engineered Sahnonella mutants showed that deletion of SopE attenuated the pathogen's ability to deplete host-cell InsP(5) and remodel the cytoskeleton. We pursued these observations: In SopE-transfected host-cells, membrane ruffling was induced, but SopE did not dephosphorylate InsP(5), nor did it recruit PTEN (a cytosolic InsP(5) phosphatase) for this task. However, PTEN strengthened SopE-mediated membrane ruffling. We conclude SopE promotes host-cell InsP(5), hydrolysis only with the assistance of other Salmonella proteins. Our demonstration that Salmonella-mediated cytoskeletal modifications are independent of inositolphosphates will focus future studies on elucidating alternate pathogenic consequences of InsP(5) metabolism, including ion channel conductance and apoptosis. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 DHSS, Natl Inst Environm Hlth Sci, Inositol Signaling Sect, NIH, Res Triangle Pk, NC 27709 USA. DHSS, Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), DHSS, Natl Inst Environm Hlth Sci, Inositol Signaling Sect, NIH, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov FU Intramural NIH HHS [Z01 ES080046-19] NR 38 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 20 PY 2006 VL 580 IS 7 BP 1709 EP 1715 DI 10.1016/j.febslet.2006.02.019 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 026KR UT WOS:000236338300003 PM 16500648 ER PT J AU Dutton, AS Suhrada, CP Miranda, KM Wink, DA Fukuto, JM Houk, KN AF Dutton, AS Suhrada, CP Miranda, KM Wink, DA Fukuto, JM Houk, KN TI Mechanism of pH-dependent decomposition of monoalkylamine diazeniumdiolates to form HNO and NO, deduced from the model compound methylamine diazeniumdiolate, density functional theory, and CBS-QB3 calculations SO INORGANIC CHEMISTRY LA English DT Article ID POLARIZABLE CONTINUUM MODEL; NITRIC-OXIDE; ANGELIS SALT; AQUEOUS-SOLUTION; SODIUM TRIOXODINITRATE(II); CHEMISTRY; MOLECULES; NITROXYL; DIETHYLAMINE; PREDICTIONS AB Isopropylamine diazeniumdiolate, IPA/NO, the product of the reaction of isopropylamine and nitric oxide, NO, decomposes in a pH-dependent manner to afford nitroxyl, HNO, in the pH range of 13 to above 5, and NO below pH 7. Theoretical studies using B3LYP/6-311+G(d) density functional theory, the polarizable continuum and conductor-like polarizable continuum solvation models, and the high-accuracy CBS-QB3 method on the simplified model compound methylamine diazeniumdiolate predict a mechanism involving HNO production via decomposition of the unstable tautomer MeNN+(O-)NHO-, The production of NO at lower pH is predicted to result from fragmentation of the amide/NO adduct upon protonation of the amine nitrogen. C1 Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Hlth Sci Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Houk, KN (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. EM houk@chem.ucla.edu RI Miranda, Katrina/B-7823-2009; Liu, Peng/D-1233-2013 FU NIGMS NIH HHS [R01 GM059446, R01 GM059446-09] NR 31 TC 34 Z9 35 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD MAR 20 PY 2006 VL 45 IS 6 BP 2448 EP 2456 DI 10.1021/ic051505z PG 9 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 023IG UT WOS:000236119700022 PM 16529464 ER PT J AU Engels, EA Brock, MV Chen, JB Hooker, CM Gillison, M Moore, RD AF Engels, EA Brock, MV Chen, JB Hooker, CM Gillison, M Moore, RD TI Elevated incidence of lung cancer among HIV-infected individuals SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA ID ACTIVE ANTIRETROVIRAL THERAPY; RISK-FACTORS; AIDS; IMMUNODEFICIENCY; SMOKING; COHORT; TOBACCO; DEFICIENCY; CARCINOMA; INCREASE AB Purpose People with HIV infection in the United States frequently smoke tobacco. We sought to characterize lung cancer incidence among HIV-infected individuals, examine whether cancer risk was related to HIV-induced immunosuppression, and assess whether the high prevalence of smoking explained elevated risk. Methods We conducted a retrospective cohort study at an HIV specialty clinic in Baltimore, MID (1989-2003). Incident lung cancers were identified using hospital records. We used negative binomial regression to compare incidence across subgroups defined by demographics, use of highly active antiretroviral therapy (HAART), and HIV markers. Standardized incidence ratios (SIRs) compared incidence with an urban reference population (Detroit, MI). We adjusted SIRs for the effect of smoking, using smoking prevalences estimated from part of the cohort and the general population. 95% CIs and P values were two sided. Results Thirty-three lung cancers were observed among 5,238 HIV-infected patients (incidence: 170 per 100,000 person-years). Incidence increased with age (P < .0001), but did not differ by sex, race, or CD4 count, Incidence tended to increase with calendar year (P = .09) and HAART use (P = .10), and was inversely related to HIV viral load (P = .03), but these associations were attenuated with age adjustment. The SIR was 4.7 (95% CI, 3.2 to 6.5) versus the general population. Twenty-eight lung cancer patients (85%) and 69% of the cohort were smokers. After smoking adjustment, risk remained elevated (SIR, 2.5; 95% CI, 1.6 to 3.5). Conclusion Lung cancer risk was substantially elevated in HIV-infected individuals. Incidence was unrelated to HIV-induced immunosuppression. Notably, incidence remained high after adjustment for smoking, suggesting the involvement of additional factors. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Ececut Blvd,EPS 8010, Bethesda, MD 20892 USA. EM engelse@exchange.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA58184]; NIDA NIH HHS [DA00432, DA11602] NR 35 TC 136 Z9 136 U1 0 U2 2 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 MAR 20 PY 2006 VL 24 IS 9 BP 1383 EP 1388 DI 10.1200/JCO.2005.03.4413 PG 6 WC Oncology SC Oncology GA 028PU UT WOS:000236501100011 PM 16549832 ER PT J AU Li, WQ Jiang, Q Aleem, E Kaldis, P Khaled, AR Durum, SK AF Li, WQ Jiang, Q Aleem, E Kaldis, P Khaled, AR Durum, SK TI IL-7 promotes T cell proliferation through destabilization of p27(Kip1) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID KINASE INHIBITOR P27(KIP1); RECEPTOR-DEFICIENT MICE; LYMPHOBLASTIC-LEUKEMIA CELLS; HOMEOSTATIC PROLIFERATION; CYCLE PROGRESSION; REGULATES PROTEOLYSIS; UBIQUITIN LIGASE; BREAST-CANCER; MEMORY CELLS; INTERLEUKIN-7 AB Interleukin (IL)-7 is required for survival and homeostatic proliferation of T lymphocytes. The survival effect of IL-7 is primarily through regulation of Bcl-2 family members; however, the proliferative mechanism is unclear. It has not been determined whether the IL-7 receptor actually delivers a proliferative signal or whether, by promoting survival, proliferation results from signals other than the IL-7 receptor. We show that in an IL-7-dependent T cell line, cells protected from apoptosis nevertheless underwent cell cycle arrest after IL-7 withdrawal. This arrest was accompanied by up-regulation of the cyclin-dependent kinase inhibitor p27(Kip1) through a posttranslational mechanism. Overexpression of p27(Kip1) induced G1 arrest in the presence of IL-7, whereas knockdown of p27(Kip1) by small interfering RNA promoted S phase entry after IL-7 withdrawal. CD4 or CD8 T cells transferred into IL-7-deficient hosts underwent G1 arrest, whereas 27(Kip1)-deficient T cells underwent proliferation. We observed that IL-7 withdrawal activated protein kinase C (PKC)theta and that inhibition of PKC theta with a pharmacological inhibitor completely blocked the rise of p27(Kip1) and rescued cells from G1 arrest. The conventional pathway to breakdown of p27(Kip1) is mediated by S phase kinase-associated protein 2; however, our evidence suggests that PKC theta acts via a distinct, unknown pathway inducing G1 arrest after IL-7 withdrawal from T cells. Hence, IL-7 maintains T cell proliferation through a novel pathway of p27(Kip1) regulation. C1 NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA. EM durums@mail.ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU Intramural NIH HHS NR 58 TC 53 Z9 53 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 20 PY 2006 VL 203 IS 3 BP 573 EP 582 DI 10.1084/jem.20051520 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 028WZ UT WOS:000236520800013 PM 16492801 ER PT J AU Bajenoff, M Breart, B Huang, AYC Qi, H Cazareth, J Braud, VM Germain, RN Glaichenhaus, N AF Bajenoff, M Breart, B Huang, AYC Qi, H Cazareth, J Braud, VM Germain, RN Glaichenhaus, N TI Natural killer cell behavior in lymph nodes revealed by static and real-time imaging SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HIGH ENDOTHELIAL VENULES; DENDRITIC CELLS; IN-VIVO; NK CELLS; LEISHMANIA-MAJOR; VIRAL-INFECTION; CUTTING EDGE; IFN-GAMMA; T-CELLS; ACTIVATION AB Natural killer (NK) cells promote dendritic cell (DC) maturation and influence T cell differentiation in vitro. To better understand the nature of the putative interactions among these cells in vivo during the early phases of an adaptive immune response, we have used immunohistochemical analysis and dynamic intravital imaging to study NK cell localization and behavior in lymph nodes (LNs) in the steady state and shortly after infection with Leishmania major. In the LNs of naive mice, NK cells reside in the medulla and the paracortex, where they closely associate with DCs. In contrast to T cells, intravital microscopy revealed that NK cells in the superficial regions of LNs were slowly motile and maintained their interactions with DCs over extended times in the presence or absence of immune-activating signals. L. major induced NK cells to secrete interferon-gamma and to be recruited to the paracortex, where concomitant CD4 T cell activation occurred. Therefore, NK cells form a reactive but low mobile network in a strategic area of the LN where they can receive inflammatory signals, interact with DCs, and regulate colocalized T cell responses. C1 Univ Nice, INSERM, F-06560 Valbonne, France. Univ Nice, CNRS, UMR6097, F-06560 Valbonne, France. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Bajenoff, M (reprint author), Univ Nice, INSERM, E03-44, F-06560 Valbonne, France. EM bajenoff@ipmc.cnrs.fr RI Qi, Hai/A-3955-2009; braud, veronique/I-4597-2013; Breart, Beatrice/M-7123-2014; OI braud, veronique/0000-0001-8213-3947; Huang, Alex/0000-0002-5701-4521 FU Intramural NIH HHS NR 40 TC 184 Z9 191 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 20 PY 2006 VL 203 IS 3 BP 619 EP 631 DI 10.1084/jem.20051474 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 028WZ UT WOS:000236520800017 PM 16505138 ER PT J AU Usui, T Preiss, JC Kanno, Y Yao, ZJ Bream, JH O'Shea, JJ Strober, W AF Usui, T Preiss, JC Kanno, Y Yao, ZJ Bream, JH O'Shea, JJ Strober, W TI T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERFERON-GAMMA; CELL-DIFFERENTIATION; IL-12R-BETA-2 CHAIN; LINEAGE COMMITMENT; SIGNAL TRANSDUCER; CUTTING EDGE; EXPRESSION; STAT4; ACTIVATOR; MICE AB T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT) 4, T-bet, and GATA-3. Here we show that CD4(+) cells from T-bet(-/-) mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4-blockade of IL-4 receptor (R) signaling. In addition, under these conditions, Th1 cells from T-bet(-/-) mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet(-/-) cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12R beta 2 chain unless GATA-3 levels or function is regulated by T-bet. Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov RI Kanno, Yuka/B-5802-2013 NR 32 TC 190 Z9 206 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 20 PY 2006 VL 203 IS 3 BP 755 EP 766 DI 10.1084/jem.20052165 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 028WZ UT WOS:000236520800029 PM 16520391 ER PT J AU Suffia, IJ Reckling, SK Piccirillo, CA Goldszmid, RS Belkaid, Y AF Suffia, IJ Reckling, SK Piccirillo, CA Goldszmid, RS Belkaid, Y TI Infected site-restricted Foxp3(+) natural regulatory T cells are specific for microbial antigens SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; LEISHMANIA-MAJOR; DENDRITIC CELLS; IMMUNE-RESPONSES; CUTTING EDGE; IN-VITRO; CD4(+); VIVO; PROLIFERATION AB Natural regulatory T (T reg) cells are involved in control of the immune response, including response to pathogens. Previous work has demonstrated that the repertoire of natural T reg cells may be biased toward self-antigen recognition. Whether they also recognize foreign antigens and how this recognition contributes to their function remain unknown. Our studies addressed the antigenic specificity of natural T reg cells that accumulate at sites of chronic infection with Leishmania major in mice. Our results support the idea that natural T reg cells are able to respond specifically to foreign antigens in that they strongly proliferate in response to Leishmania-infected dendritic cells, they maintain Foxp3 expression, and Leishmania-specific T reg cell lines can be generated from infected mice. Surprisingly, the majority of natural T reg cells at the infected site are Leishmania specific. Further, we showed that parasite-specific natural T reg cells are restricted to sites of infection and that their survival is strictly dependent on parasite persistence. C1 NIAID, Mucosal Immunol Unit, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. McGill Univ, Dept Microbiol, Montreal, PQ H3A 2BA, Canada. McGill Univ, Dept Immunol, Montreal, PQ H3A 2BA, Canada. McGill Univ, Ctr Study Host Resistance, Montreal, PQ H3A 2BA, Canada. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [R01 AI057992, R01AI057992-01] NR 41 TC 222 Z9 230 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 20 PY 2006 VL 203 IS 3 BP 777 EP 788 DI 10.1084/jem.20052056 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 028WZ UT WOS:000236520800031 PM 16533885 ER PT J AU Focarelli, ML Montagna, C Colombo, R Ried, T Vezzoni, P Musio, A AF Focarelli, ML Montagna, C Colombo, R Ried, T Vezzoni, P Musio, A TI SMC1 inhibition results in FRA3B expression but has no effect on its delayed replication SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE fragile sites; FRA3B; SMC1; delayed replication ID COMMON FRAGILE SITES; DNA-POLYMERASE-ALPHA; HUMAN-CHROMOSOMES; S-PHASE; CELL-LINES; INSTABILITY; RECOMBINATION; CHECKPOINT; PESTICIDES; PROTEINS AB Cellular processes involved in fragile site expression have been investigated by studying the effect on the replication pattern of the commonest fragile site FRA3B of RNA interference (RNAi)-mediated sister maintenance chromosome 1 (SMC1) inhibition in normal human fibroblasts. Replication timing of FRA3B in G, was studied by bromodeoxyuridine (BrdU) labeling for the final 2h of cell culture whereas in the S phase was investigated by a fluorescence in situ hybridization (FISH)-based approach through the analysis of clones spanning the FRA3B region. Results showed that FRA3B is normally late replicated even though it is not expressed in untreated cells. On the other hand, SMC1 inhibition leads to FRA3B expression even if the percent of late replicated cells is comparable to control cells. These results obtained by analysing the commonest fragile site suggest that SMC1 plays a role in protecting late replicating regions from stresses occurring in the final steps of genome replication and that delayed replication is necessary but not sufficient for inducing fragile site expression. (c) 2005 Elsevier B.V. All rights reserved. C1 CNR, Ist Tecnol Biomed, Dipartimento Gen Umano, I-20090 Milan, Italy. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Univ Cattolica Sacro Cuore, Lab Biol Mol & Genet Umana, I-20123 Milan, Italy. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Musio, A (reprint author), CNR, Ist Tecnol Biomed, Dipartimento Gen Umano, Via Fratelli Cervi,93, I-20090 Milan, Italy. EM antonio.musio@itb.cnr.it NR 27 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 20 PY 2006 VL 595 IS 1-2 BP 23 EP 28 DI 10.1016/j.mrfmmm.2005.09.002 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 022IQ UT WOS:000236049300004 PM 16242161 ER PT J AU Gardell, LR King, T Ossipov, MH Rice, KC Lai, J Vanderah, TW Porreca, F AF Gardell, LR King, T Ossipov, MH Rice, KC Lai, J Vanderah, TW Porreca, F TI Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery SO NEUROSCIENCE LETTERS LA English DT Article DE hyperalgesia; tactile hyperesthesia; antinociceptive tolerance; opioid; dynorphin ID EXCITATORY AMINO-ACIDS; LONG-LASTING ALLODYNIA; NERVE-INJURED RATS; SPINAL DYNORPHIN; NEUROPATHIC PAIN; DESCENDING FACILITATION; MORPHINE-METABOLISM; ABNORMAL PAIN; HUMAN-BRAIN; INCREASES AB Opiates are commonly used to treat moderate to severe pain and can be used over prolonged periods in states of chronic pain such as those associated with cancer. In addition, to analgesic actions, studies show that opiate administration can paradoxically induce hyperalgesia. At the pre-clinical level, such hyperalgesia is associated with numerous pronociceptive neuroplastic changes within the primary afferent fibers and the spinal cord. In rodents, sustained opiate administration also induces antinociceptive tolerance. The mechanisms by which prolonged opiate exposure induces hyperalgesia and the relationship of this state to antinociceptive tolerance remain unclear. The present study was aimed at determining whether sustained opiate-induced hyperalgesia, associated neuroplasticity and antinociceptive tolerance are the result of specific opiate interaction at opiate receptors. Enantiomers of oxymorphone, a mu opioid receptor agonist, were administered to rats by spinal infusion across 7 days. Sustained spinal administration of (-)-oxymorphone, but not its inactive enantiomer (+)-oxymorphone or vehicle, upregulated spinal dynorphin content, produced thermal and tactile hypersensitivity, and produced antinociceptive tolerance. These results indicate that these pronociceptive actions of sustained opiate administration require specific interaction with opiate receptors and are unlikely to be the result of accumulation of potentially excitatory metabolic products. While the precise mechanisms, which may account for these pronociceptive changes remain to be unraveled, the present data point to plasticity initiated by opiate receptor interaction. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Arizona, Coll Med, Hlth Sci Ctr, Dept Pharmacol, Tucson, AZ 85724 USA. Natl Inst Diabet & Digest & Kidney Dis, Lab Med Chem, NIH, Bethesda, MD USA. RP Porreca, F (reprint author), Univ Arizona, Coll Med, Hlth Sci Ctr, Dept Pharmacol, Tucson, AZ 85724 USA. EM frankp@u.arizona.edu FU NIDA NIH HHS [P01 DA006284] NR 45 TC 55 Z9 55 U1 0 U2 1 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 MAR 20 PY 2006 VL 396 IS 1 BP 44 EP 49 DI 10.1016/j.neulet.2005.11.009 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 017VU UT WOS:000235722200009 PM 16343768 ER PT J AU Madhi, SA Cutland, C Zhu, YW Hackell, JG Newman, F Blackburn, N Murphy, BR Belshe, RB Karron, RA Deatly, AM Gruber, WC Bernstein, DI Wright, PF AF Madhi, SA Cutland, C Zhu, YW Hackell, JG Newman, F Blackburn, N Murphy, BR Belshe, RB Karron, RA Deatly, AM Gruber, WC Bernstein, DI Wright, PF TI Transmissibility, infectivity and immunogenicity of a live human parainfluenza type 3 virus vaccine (HP1V3cp45) among susceptible infants and toddlers SO VACCINE LA English DT Article DE parainfluenza virus type 3; vaccine; live-attenuated; transmissibility; immunogenicity; safety ID RESPIRATORY SYNCYTIAL VIRUS; YOUNG-CHILDREN; ATTENUATION PHENOTYPES; CANDIDATE VACCINE; WEANLING HAMSTERS; HEALTHY INFANTS; ANTIBODY; MUTANTS; PIV3; OLD AB Background: This study examined the transmissibility between young children of an intranasally administered live attenuated human parainfluenza virus type 3 (HPIV3)-cp45 vaccine candidate. Methods: Eighty subjects were enrolled in playgroups among whom there was at least one infected vaccinee in close contact with a seronegative placebo recipient over 21 days without a confounding infection with wtHPIV3. Following vaccination viral cultures were obtained on nine occasions to detect shedding and transmission of HPIV3cp45. Serum antibody titers were measured before and 7 weeks after vaccination. Results: No child fulfilled the criteria for transmission of HPIV3cp45 giving a risk of transmission of 0.04 (95% Cl 0.01-0.19), hence establishing that HPIV3cp45 is less infectious than wtHPIV3 and risk of transmission is not a limitation to further clinical development of this vaccine candidate. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Witwatersrand, MRC, Resp & Meningeal Pathogens Res Unit, ZA-2050 Wits, South Africa. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Wyeth Res, Viral Vaccines, Pearl River, NY USA. St Louis Univ, Div Infect Dis & Immunol, St Louis, MO 63103 USA. Natl Inst Communicable Dis, Johannesburg, South Africa. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Madhi, SA (reprint author), Chris Hani Baragwanath Hosp, Dept Pediat, ZA-2013 Johannesburg, South Africa. EM madhis@hivsa.com NR 29 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 20 PY 2006 VL 24 IS 13 BP 2432 EP 2439 DI 10.1016/j.vaccine.2005.12.002 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IT UT WOS:000236259800026 PM 16406170 ER PT J AU Shearman, AM Cooper, JA Kotwinski, PJ Miller, GJ Humphries, SE Ardlie, KG Jordan, B Irenze, K Lunetta, KL Schuit, SCE Uitterlinden, AG Pols, HAP Demissie, S Cupples, LA Mendelsohn, ME Levy, D Housman, DE AF Shearman, AM Cooper, JA Kotwinski, PJ Miller, GJ Humphries, SE Ardlie, KG Jordan, B Irenze, K Lunetta, KL Schuit, SCE Uitterlinden, AG Pols, HAP Demissie, S Cupples, LA Mendelsohn, ME Levy, D Housman, DE TI Estrogen receptor alpha gene variation is associated with risk of myocardial infarction in more than seven thousand men from five cohorts SO CIRCULATION RESEARCH LA English DT Editorial Material DE genetics; myocardial infarction; estrogen receptor; risk factors ID HORMONE REPLACEMENT THERAPY; CORONARY-ARTERY-DISEASE; POLYMORPHISMS; GENOTYPE; WOMEN AB Understanding the mechanisms by which estrogens affect cardiovascular disease risk, including the role of variation in the gene for estrogen receptor alpha(ESR1), may be key to new treatment strategies. We investigated whether the CC genotype at ESR1 c. 454-397T > C is associated with increased risk among men. Study of more than 7000 whites in 5 cohorts from 4 countries provided evidence that genotype CC, present in roughly 20% of individuals, is a risk factor for nonfatal acute myocardial infarction (odds ratio = 1.44; P < 0.0001), after adjustment for established cardiovascular risk factors. After exclusion of younger subjects from 2 cohorts, because of age interaction, the odds ratio increased (to 1.63). C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. UCL Royal Free & UCL Med Sch, Rayne Inst, Dept Med, Ctr Cardiovasc Genet, London, England. Inst Child Hlth, Portex Anaesthesia Intens Therapy & Resp Med Unit, London, England. Wofson Inst Prevent Med, MRC, Cardiovasc Res Grp, London, England. Genom Collaborat, Cambridge, MA USA. Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Shearman, AM (reprint author), MIT, Ctr Canc Res, E17-536, Cambridge, MA 02139 USA. EM shearman@mit.edu RI Humphries, Stephen/C-5075-2008; OI Lunetta, Kathryn/0000-0002-9268-810X; Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [P50-HL63494, HL-33014, HL-54502, N01-HC-25195, R01-HL65230] NR 17 TC 63 Z9 64 U1 0 U2 14 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 MAR 17 PY 2006 VL 98 IS 5 BP 590 EP 592 DI 10.1161/01.RES.0000210578.62102.a6 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 022FZ UT WOS:000236042000007 PM 16484614 ER PT J AU Yoon, SO Lee, TS Kim, SJ Jang, MH Kang, YJ Park, JH Kim, KS Lee, HS Ryu, CJ Gonzales, NR Kashmiri, SVS Lim, SM Choi, CW Hong, HJ AF Yoon, SO Lee, TS Kim, SJ Jang, MH Kang, YJ Park, JH Kim, KS Lee, HS Ryu, CJ Gonzales, NR Kashmiri, SVS Lim, SM Choi, CW Hong, HJ TI Construction, affinity maturation, and biological characterization of an anti-tumor-associated glycoprotein-72 humanized antibody SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; METASTATIC COLON-CARCINOMA; HEPATITIS-B-VIRUS; RADIOIMMUNOTHERAPY TRIAL; ANTICARCINOMA ANTIBODY; PHASE-I; IMMUNOGENICITY; CC49; BINDING; B72.3 AB The tumor-associated glycoprotein (TAG)-72 is expressed in the majority of human adenocarcinomas but is rarely expressed in most normal tissues, which makes it a potential target for the diagnosis and therapy of a variety of human cancers. Here we describe the construction, affinity maturation, and biological characterization of an anti-TAG-72 humanized antibody with minimum potential immunogenicity. The humanized antibody was constructed by grafting only the specificity-determining residues (SDRs) within the complementarity-determining regions (CDRs) onto homologous human immunoglobulin germ line segments while retaining two mouse heavy chain framework residues that support the conformation of the CDRs. The resulting humanized antibody ( AKA) showed only about 2-fold lower affinity compared with the original murine monoclonal antibody CC49 and 27-fold lower reactivity to patient serum compared with the humanized antibody HuCC49 that was constructed by CDR grafting. The affinity of AKA was improved by random mutagenesis of the heavy chain CDR3 (HCDR3). The highest affinity variant (3E8) showed 22-fold higher affinity compared with AKA and retained the original epitope specificity. Mutational analysis of the HCDR3 residues revealed that the replacement of Asn(97) by isoleucine or valine was critical for the affinity maturation. The 3E8 labeled with I-125 or I-131 showed efficient tumor targeting or therapeutic effects, respectively, in athymic mice with human colon carcinoma xenografts, suggesting that 3E8 may be beneficial for the diagnosis and therapy of tumors expressing TAG-72. C1 Korea Inst Radiol & Med Sci, Dept Nucl Med, Seoul 139706, South Korea. Korea Inst Radiol & Med Sci, Lab Cyclotron Applicat, Seoul 139706, South Korea. Aprogen Inc, Korea Res Inst Biosci & Biotechnol, Lab Antibody Engn, Taejon 305333, South Korea. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Choi, CW (reprint author), Korea Inst Radiol & Med Sci, Dept Nucl Med, 215-4 Gongneung, Seoul 139706, South Korea. EM cwchoi@kcch.re.kr; hjhong@kribb.re.kr NR 45 TC 29 Z9 32 U1 2 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 MAR 17 PY 2006 VL 281 IS 11 BP 6985 EP 6992 DI 10.1074/jbc.M511165200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BY UT WOS:000236030900011 PM 16407221 ER PT J AU Mendiratta, G Eriksson, PR Shen, CH Clark, DJ AF Mendiratta, G Eriksson, PR Shen, CH Clark, DJ TI The DNA-binding domain of the yeast Spt10p activator includes a zinc finger that is homologous to foamy virus integrase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; CHROMATIN-STRUCTURE; SPT21 GENES; PROTEIN; ACETYLATION; MUTATIONS; IDENTIFICATION; RECOGNITION; HISTONE-H3 AB The yeast SPT10 gene encodes a putative histone acetyltransferase that binds specifically to pairs of upstream activating sequence (UAS) elements found only in the histone gene promoters. Here, we demonstrate that the DNA-binding domain of Spt10p is located between residues 283 and 396 and includes a His(2)-Cys(2) zinc finger. The binding of Spt10p to the histone UAS is zinc-dependent and is disabled by a zinc finger mutation (C388S). The isolated DNA-binding domain binds to single histone UAS elements with high affinity. In contrast, full-length Spt10p binds with high affinity only to pairs of UAS elements with very strong positive cooperativity and is unable to bind to a single UAS element. This implies the presence of a "blocking" domain in full-length Spt10p, which forces it to search for a pair of UAS elements. Chromatin immunoprecipitation experiments indicate that, unlike wild-type Spt10p, the C388S protein does not bind to the promoter of the gene encoding histone H2A (HTA1) in vivo. The C388S mutant has a phenotype similar to that of the spt10 Delta mutant: poor growth and global aberrations in gene expression. Thus, the C388S mutation disables the DNA-binding function of Spt10p in vitro and in vivo. The zinc finger of Spt10p is homologous to that of foamy virus integrase, perhaps suggesting that this integrase is also a sequence-specific DNA-binding protein. C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. CUNY Coll Staten Isl, Dept Biol, Staten Isl, NY 10314 USA. RP Clark, DJ (reprint author), NICHD, Lab Mol Growth Regulat, NIH, Bldg 6A,Rm 2A14,6 Ctr Dr, Bethesda, MD 20892 USA. EM clarkda@mail.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [1R15 GM 67730-01] NR 30 TC 15 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 MAR 17 PY 2006 VL 281 IS 11 BP 7040 EP 7048 DI 10.1074/jbc.M511416200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BY UT WOS:000236030900017 PM 16415340 ER PT J AU Kono, M Dreier, JL Ellis, JM Allende, ML Kalkofen, DN Sanders, KM Bielawski, J Bielawska, A Hannun, YA Proia, RL AF Kono, M Dreier, JL Ellis, JM Allende, ML Kalkofen, DN Sanders, KM Bielawski, J Bielawska, A Hannun, YA Proia, RL TI Neutral ceramidase encoded by the Asah2 gene is essential for the intestinal degradation of sphingolipids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 1,2-DIMETHYLHYDRAZINE-TREATED CF1 MICE; ALKALINE SPHINGOMYELINASE ACTIVITY; HUMAN ACID CERAMIDASE; FULL-LENGTH CDNA; MOLECULAR-CLONING; GASTROINTESTINAL-TRACT; COLON-CANCER; CRYPT FOCI; METABOLISM; RAT AB Complex sphingolipids are abundant as eukaryotic cell membrane components, whereas their metabolites, in particular ceramide, sphingosine, and sphingosine 1-phosphate, are involved in diverse cell signaling processes. In mammals, degradation of ceramide by ceramidase yields sphingosine, which is phosphorylated by the action of sphingosine kinase to generate sphingosine 1-phosphate. Therefore, ceramidases are key enzymes in the regulation of the cellular levels of ceramide, sphingosine, and sphingosine 1-phosphate. To explore the physiological functions of a neutral ceramidase with diverse cellular locations, we disrupted the Asah2 gene in mice. Asah2 null mice have a normal life span and do not show obvious abnormalities or major alterations in total ceramide levels in tissues. The Asah2-encoded neutral ceramidase is highly expressed in the small intestine along the brush border, suggesting that the neutral ceramidase may be involved in a pathway for the digestion of dietary sphingolipids. Indeed, Asah2 null mice were deficient in the intestinal degradation of ceramide. Thus, the results indicate that the Asah2-encoded neutral ceramidase is a key enzyme for the catabolism of dietary sphingolipids and regulates the levels of bioactive sphingolipid metabolites in the intestinal tract. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU Intramural NIH HHS; NIDDK NIH HHS [DK 59340] NR 43 TC 64 Z9 66 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 MAR 17 PY 2006 VL 281 IS 11 BP 7324 EP 7331 DI 10.1074/jbc.M508382200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BY UT WOS:000236030900051 PM 16380386 ER PT J AU Hamburgh, ME Curr, KA Monaghan, M Rao, VR Tripathi, S Preston, BD Sarafianos, S Arnold, E Darden, T Prasad, VR AF Hamburgh, ME Curr, KA Monaghan, M Rao, VR Tripathi, S Preston, BD Sarafianos, S Arnold, E Darden, T Prasad, VR TI Structural determinants of slippage-mediated mutations by human immunodeficiency virus type 1 reverse transcriptase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE ANALOG-RESISTANCE; ALANINE-SCANNING MUTAGENESIS; POLYMERASE FIDELITY; DNA-SYNTHESIS; ERROR SPECIFICITY; CRYSTAL-STRUCTURE; THUMB SUBDOMAIN; GLU-89 RESIDUE; MINOR-GROOVE; HIV-1 RT AB Single-base deletions at nucleotide runs or - 1 frameshifting by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) result from template slippage during polymerization. In crystal structures of HIV-1 RT complexed with DNA-DNA template-primer, the palm subdomain in the template cleft contacts the template backbone near the proposed site of slippage via the Glu(89) side chain. We investigated the role of Glu(89) in frameshifting by perturbing this interaction. Substitutions with Asp, Gly, Ala, Val, Ser, Thr, Asn, or Lys were created in recombinant HIV RT, and frameshift frequencies of the resulting mutant RTs were measured. All substitutions led to reduced -1 frameshifting by HIV-1 RT (2-40-fold). Interestingly, the suppression of -1 frameshifting frequently coincided with an enhancement of -1 frameshifting (3-47-fold) suggesting that Glu(89) can influence the slippage of both strands. Glu(89) substitutions also led to reduced rates of dNTP mis-incorporation that paralleled reductions in -1 frameshifting, suggesting a common structural mechanism for both classes of RT error. Our results reveal a major influence of Glu(89) on slippage-mediated errors and dNTP incorporation fidelity. The crystal structure of HIV-1 RT reveals a salt bridge between Glu(89) and Lys(154), which may facilitate -1 frameshifting; this concept is supported by the observed reduction in -1 frameshifting for K154A and K154R mutants. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Biol Chem, Piscataway, NJ 08854 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27707 USA. RP Prasad, VR (reprint author), 1300 Morris Pk Ave,Rm GB 401, Bronx, NY 10461 USA. EM prasad@aecom.yu.edu OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [AI 30861, R37 AI030861]; NIGMS NIH HHS [T32 GM 07461] NR 40 TC 14 Z9 15 U1 1 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 MAR 17 PY 2006 VL 281 IS 11 BP 7421 EP 7428 DI 10.1074/jbc.M511380200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BY UT WOS:000236030900063 PM 16423828 ER PT J AU Chen, ZQ Dong, JS Ishimura, A Daar, I Hinnebusch, AG Dean, M AF Chen, ZQ Dong, JS Ishimura, A Daar, I Hinnebusch, AG Dean, M TI The essential vertebrate ABCE1 protein interacts with eukaryotic initiation factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNASE-L INHIBITOR; 2-5A-DEPENDENT RNASE; SEQUENCE ALIGNMENT; XENOPUS-OOCYTES; TRANSLATION; INTERFERON; PATHWAY; CELLS; BIOGENESIS; EVOLUTION AB The ABCE1 gene is a member of the ATP-binding cassette (ABC) multigene family and is composed of two nucleotide binding domains and an N-terminal Fe-S binding domain. The ABCE1 gene encodes a protein originally identified for its inhibition of ribonuclease L, a nuclease induced by interferon in mammalian cells. The protein is also required for the assembly of the HIV and SIV gag polypeptides. However, ABCE1 is one of the most highly conserved proteins and is found in one or two copies in all characterized eukaryotes and archaea. Yeast ABCE1/RLI1 is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. We show here that the human ABCE1 protein is essential for in vitro and in vivo translation of mRNA and that it binds to eIF2 alpha and eIF5. Inhibition of the Xenopus ABCE1 arrests growth at the gastrula stage of development, consistent with a block in translation. The human ABCE1 gene contains 16 introns, and the extremely high degree of amino acid identity allows the evolution of its introns to be examined throughout eukaryotes. The demonstration that ABCE1 plays a role in vertebrate translation initiation extends the known functions of this highly conserved protein. Translation is a highly regulated process important to development and pathologies such as cancer, making ABCE1 a potential target for therapeutics. The evolutionary analysis supports a model in which an ancestral eukaryote had large number of introns and that many of these introns were lost in non-vertebrate lineages. C1 NCI, Lab Genom Divers, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Dean, M (reprint author), NCI, Lab Genom Divers, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Daar, Ira/0000-0003-2657-526X FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 24 TC 76 Z9 87 U1 2 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 MAR 17 PY 2006 VL 281 IS 11 BP 7452 EP 7457 DI 10.1074/jbc.M510603200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BY UT WOS:000236030900067 PM 16421098 ER PT J AU Prabakaran, P Gan, JH Wu, YQ Zhang, MY Dimitrov, DS Ji, XH AF Prabakaran, P Gan, JH Wu, YQ Zhang, MY Dimitrov, DS Ji, XH TI Structural mimicry of CD4 by a cross-reactive HIV-1 neutralizing antibody with CDR-H2 and H3 containing unique motifs SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV; antibody; crystal structure; gp120; vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; COMPLEMENTARITY-DETERMINING REGION; GP120 ENVELOPE GLYCOPROTEIN; PROTEIN-PROTEIN DOCKING; BINDING-SITE; TYPE-1 GP120; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; FAB FRAGMENT AB Human immunodeficiency virus (HIV) entry into cells is initiated by the binding of its envelope glycoprotein (Env) gp120 to receptor CD4. Antibodies that bind to epitopes overlapping the CD4-binding site (CD4bs) on gpl20 can prevent HIV entry by competing with cell-associated CD4; their ability to outcompete CD4 is a major determinant of their neutralizing potency and is proportional to their avidity. The breadth of neutralization and the likelihood of the emergence of antibody-resistant virus are critically dependent on the structure of their epitopes. Because CD4bs is highly conserved, it is reasonable to hypothesize that antibodies closely mimicking CD4 could exhibit relatively broad cross-reactivity and a high probability of preventing the emergence of resistant viruses. Previously, in a search for antibodies that mimic CD4 or the co-receptor, we identified and characterized a broadly cross-reactive HIV-neutralizing CD4bs human monoclonal antibody (hmAb), m18. Here, we describe the crystal structure of Fab m18 at 2.03 angstrom resolution, which reveals unique conformations of heavy chain complementarity-determining regions (CDRs) 2 and 3 (H2 and H3). H2 is highly bulged and lacks cross-linking interstrand hydrogen bonds observed in all four canonical structures. H3 is 17.5 angstrom long and rigid, forming an extended beta-sheet decorated with an a-turn motif bearing a phenylalanine-isoleucine fork at the apex. It shows striking similarity to the Ig CDR2-like C'C" region of the CD4 first domain D1 that dominates the binding of CD4 to gp120. Docking simulations suggest significant similarity between the m18 epitope and the CD4bs on gp120. Fab m18 does not enhance binding of CD4-induced (CD4i) antibodies, nor does it induce CD4-independent fusion mediated by the HIV Env. Thus, vaccine immunogens based on the m18 epitope structure are unlikely to elicit antibodies that could enhance infection. The structure can also serve as a basis for the design of novel, highly efficient inhibitors of HIV entry. Published by Elsevier Ltd. C1 NCI, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA. NCI, Biomol Struct Sect, Macromol Crystallog Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov; jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012; Ponraj, Prabakaran/D-6325-2011 OI Ji, Xinhua/0000-0001-6942-1514; FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01-CO-24000] NR 78 TC 19 Z9 21 U1 0 U2 4 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 MAR 17 PY 2006 VL 357 IS 1 BP 82 EP 99 DI 10.1016/j.jmb.2005.062 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 019GP UT WOS:000235823900008 PM 16426633 ER PT J AU Dudko, OK Hummer, G Szabo, A AF Dudko, OK Hummer, G Szabo, A TI Intrinsic rates and activation free energies from single-molecule pulling experiments SO PHYSICAL REVIEW LETTERS LA English DT Article ID DYNAMIC FORCE SPECTROSCOPY; ADHESION BONDS; PROTEIN; COMPLEX; CELLS; FIELD AB We present a unified framework for extracting kinetic information from single-molecule pulling experiments at constant force or constant pulling speed. Our procedure provides estimates of not only (i) the intrinsic rate coefficient and (ii) the location of the transition state but also (iii) the free energy of activation. By analyzing simulated data, we show that the resulting rates of force-induced rupture are significantly more reliable than those obtained by the widely used approach based on Bell's formula. We consider the uniqueness of the extracted kinetic information and suggest guidelines to avoid overinterpretation of experiments. C1 NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Dudko, OK (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 22 TC 389 Z9 392 U1 7 U2 106 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 MAR 17 PY 2006 VL 96 IS 10 AR 108101 DI 10.1103/PhysRevLett.96.108101 PG 4 WC Physics, Multidisciplinary SC Physics GA 022NP UT WOS:000236062800084 PM 16605793 ER PT J AU Makarova, KS Grishin, NV Shabalina, SA Wolf, YI Koonin, EV AF Makarova, Kira S. Grishin, Nick V. Shabalina, Svetlana A. Wolf, Yuri I. Koonin, Eugene V. TI A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action SO BIOLOGY DIRECT LA English DT Article ID DNA-REPAIR SYSTEM; MESSENGER-RNA; ANTISENSE RNA; SECONDARY STRUCTURE; NONCODING RNAS; PIN-DOMAIN; PSI-BLAST; C-ELEGANS; PROTEIN; REPEATS AB Background: All archaeal and many bacterial genomes contain Clustered Regularly Interspaced Short Palindrome Repeats (CRISPR) and variable arrays of the CRISPR-associated ( cas) genes that have been previously implicated in a novel form of DNA repair on the basis of comparative analysis of their protein product sequences. However, the proximity of CRISPR and cas genes strongly suggests that they have related functions which is hard to reconcile with the repair hypothesis. Results: The protein sequences of the numerous cas gene products were classified into similar to 25 distinct protein families; several new functional and structural predictions are described. Comparative-genomic analysis of CRISPR and cas genes leads to the hypothesis that the CRISPR-Cas system ( CASS) is a mechanism of defense against invading phages and plasmids that functions analogously to the eukaryotic RNA interference (RNAi) systems. Specific functional analogies are drawn between several components of CASS and proteins involved in eukaryotic RNAi, including the double-stranded RNA-specific helicase-nuclease (dicer), the endonuclease cleaving target mRNAs ( slicer), and the RNA-dependent RNA polymerase. However, none of the CASS components is orthologous to its apparent eukaryotic functional counterpart. It is proposed that unique inserts of CRISPR, some of which are homologous to fragments of bacteriophage and plasmid genes, function as prokaryotic siRNAs (psiRNA), by base-pairing with the target mRNAs and promoting their degradation or translation shutdown. Specific hypothetical schemes are developed for the functioning of the predicted prokaryotic siRNA system and for the formation of new CRISPR units with unique inserts encoding psiRNA conferring immunity to the respective newly encountered phages or plasmids. The unique inserts in CRISPR show virtually no similarity even between closely related bacterial strains which suggests their rapid turnover, on evolutionary scale. Corollaries of this finding are that, even among closely related prokaryotes, the most commonly encountered phages and plasmids are different and/or that the dominant phages and plasmids turn over rapidly. Conclusion: We proposed previously that Cas proteins comprise a novel DNA repair system. The association of the cas genes with CRISPR and, especially, the presence, in CRISPR units, of unique inserts homologous to phage and plasmid genes make us abandon this hypothesis. It appears most likely that CASS is a prokaryotic system of defense against phages and plasmids that functions via the RNAi mechanism. The functioning of this system seems to involve integration of fragments of foreign genes into archaeal and bacterial chromosomes yielding heritable immunity to the respective agents. However, it appears that this inheritance is extremely unstable on the evolutionary scale such that the repertoires of unique psiRNAs are completely replaced even in closely related prokaryotes, presumably, in response to rapidly changing repertoires of dominant phages and plasmids. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM makarova@ncbi.nlm.nih.gov; grishin@chop.swmed.edu; shabalin@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013 OI Shabalina, Svetlana/0000-0003-2272-7473 NR 75 TC 433 Z9 471 U1 23 U2 149 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD MAR 16 PY 2006 VL 1 AR 7 DI 10.1186/1745-6150-1-7 PG 26 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133SC UT WOS:000244032500001 PM 16545108 ER PT J AU Pareek, TK Kulkarni, AB AF Pareek, TK Kulkarni, AB TI Cdk5 - A new player in pain signaling SO CELL CYCLE LA English DT Article DE analgesics; Cdk5; DRG; trigeminal ganglia; morphine; MEK; nociception; p35; pain; tolerance ID CYCLIN-DEPENDENT KINASE-5; RAT SPINAL-CORD; CDC2-RELATED PROTEIN-KINASE; RECEPTOR MESSENGER-RNA; FOS-LIKE PROTEIN; INFLAMMATORY PAIN; C-FOS; NOXIOUS-STIMULATION; DOWN-REGULATION; NMDA RECEPTORS AB Cyclin-dependent kinase 5 (Cdk5) is predominantly active in postmitotic neurons. Despite its structural homology with other cyclin-dependent kinases, Cdk5 is apparently not involved in the cell cycle process. The monomeric form of Cdk5 is inactive and requires the association of p35 or p39 in order to perform its kinase activity. This kinase is essential for normal brain development and function, but uncontrolled activity of Cdk5 may lead to numerous neurodegenerative processes. Although Cdk5 activity has been implicated in several neuronal functions, its precise role in the peripheral nervous system has not been determined. Recently we reported for the first time the essential role for Cdk5 in pain signaling (Pareek et al., PNAS 2006; 103: 791 - 6). Altered nociceptive responses to basal thermal noxious stimuli in p35 knockout (p35(-/-)) and p35-overexpresing transgenic mice (Tgp35) have established the important role of this gene in the nociceptive process. Here, we report that Cdk5 regulates mitogen-activated protein kinase kinase1/2 (MEK1/2) activity through a negative feedback loop during the peripheral inflammatory response. Moreover a differential nociceptive response after chronic morphine exposure in p35(-/-) and Tgp35 mice suggests that Cdk5 activity is important for opioid tolerance. In conclusion, our data indicate important molecular roles for Cdk5 in pain signaling and opioid tolerance, which makes it a potential target for analgesic drug development. C1 Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr,Bldg 30,Room 122-132,MSC 4395, Bethesda, MD 20892 USA. EM ak40m@nih.gov OI Pareek, Tej/0000-0001-5134-1647 FU Intramural NIH HHS NR 48 TC 34 Z9 37 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 16 PY 2006 VL 5 IS 6 BP 585 EP 588 DI 10.4161/cc.5.6.2578 PG 4 WC Cell Biology SC Cell Biology GA 053CU UT WOS:000238282400009 PM 16552189 ER PT J AU DeRouchey, J Walker, GF Wagner, E Radler, JO AF DeRouchey, J Walker, GF Wagner, E Radler, JO TI Decorated rods: A "bottom-up" self-assembly of monomolecular DNA complexes SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID FLUORESCENCE CORRELATION SPECTROSCOPY; GENE DELIVERY; POLYETHYLENE-GLYCOL; POLYMER BRUSHES; IN-VIVO; MACROMOLECULES; CIRCULATION; TRANSITION; COPOLYMERS; MOLECULES AB Fluorescence correlation spectroscopy (FCS) and gel electrophoresis measurements are performed to investigate both the number and size of complexes of linear double-stranded DNA (dsDNA) fragments with 1: 1 diblock copolymers consisting of a cationic moiety, branched polyethyleneimine (bPEI) of 2, 10, or 25 kDa, covalently bound to a neutral shielding moiety, poly(ethylene glycol) (PEG; 20 kDa). By systematically decreasing the bPEI length, the PEG grafting density along the DNA chain can be directly controlled. For 25 and 10 kDa bPEI-PEG copolymers, severe aggregation is observed despite the presence of the shielding PEG. Upon decreasing the bPEI length to 2 kDa, controlled self-assembly of monomolecular DNA nanoparticles is observed. The resulting complexes are in quantitative agreement with a theoretical model based on a single DNA encased in a dense PEG polymer brush layer. The resulting PEGylated complexes show high stability against both salt and protein and hence are of potential use for in vivo gene delivery studies. C1 Univ Munich, Dept Phys, D-80539 Munich, Germany. Univ Munich, Dept Pharmaceut Biol Biotechnol, D-80539 Munich, Germany. RP DeRouchey, J (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM deroucja@mail.nih.gov RI DeRouchey, Jason/B-3437-2009; DeRouchey, Jason/C-5907-2011; Wagner, Ernst/A-7435-2012 OI DeRouchey, Jason/0000-0002-3624-4432; Wagner, Ernst/0000-0001-8413-0934 NR 42 TC 27 Z9 27 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 16 PY 2006 VL 110 IS 10 BP 4548 EP 4554 DI 10.1021/jp.053760a PG 7 WC Chemistry, Physical SC Chemistry GA 022TB UT WOS:000236077600012 PM 16526683 ER PT J AU Ishibashi, T Dakin, KA Stevens, B Lee, PR Kozlov, SV Stewart, CL Fields, RD AF Ishibashi, T Dakin, KA Stevens, B Lee, PR Kozlov, SV Stewart, CL Fields, RD TI Astrocytes promote myelination in response to electrical impulses SO NEURON LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; CILIARY NEUROTROPHIC FACTOR; WHITE-MATTER ARCHITECTURE; ACTION-POTENTIALS; ALEXANDER-DISEASE; NEURAL IMPULSES; EXPRESSION; CNS; OLIGODENDROCYTES; MATURATION AB Myelin, the insulating layers of membrane wrapped around axons by oligodendrocytes, is essential for normal impulse conduction. It forms during late stages of fetal development but continues into early adult life. Myelination correlates with cognitive development and can be regulated by impulse activity through unknown molecular mechanisms. Astrocytes do not form myelin, but these nonneuronal cells can promote myelination in ways that are not understood. Here, we identify a link between myelination, astrocytes, and electrical impulse activity in axons that is mediated by the cytokine leukemia inhibitory factor (LIF). These findings show that LIF is released by astrocytes in response to ATP liberated from axons firing action potentials, and LIF promotes myelination by mature oligodendrocytes. This activity-dependent mechanism promoting myelination could regulate myelination according to functional activity or environmental experience and may offer new approaches to treating demyelinating diseases. C1 NICHHD, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. NCI, Lab Canc & Dev Biol, Frederick, MD 21702 USA. RP Fields, RD (reprint author), NICHHD, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD000713-11] NR 36 TC 312 Z9 328 U1 0 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 16 PY 2006 VL 49 IS 6 BP 823 EP 832 DI 10.1016/j.neuron.2006.02.006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 024WQ UT WOS:000236227500011 PM 16543131 ER PT J AU Plaut, M Valentine, MD AF Plaut, M Valentine, MD TI Allergic rhinitis - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIAID, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. RP Plaut, M (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mplaut@niaid.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 16 PY 2006 VL 354 IS 11 BP 1206 EP 1206 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 021KI UT WOS:000235981700033 ER PT J AU Shen, M Boffetta, P Olsen, JH Andersen, A Hemminki, K Pukkala, E Tracey, E Brewster, DH McBride, ML Pompe-Kirn, V Kliewer, EV Tonita, JM Chia, KS Martos, C Jonasson, JG Colin, D Scelo, G Brennan, P AF Shen, M Boffetta, P Olsen, JH Andersen, A Hemminki, K Pukkala, E Tracey, E Brewster, DH McBride, ML Pompe-Kirn, V Kliewer, EV Tonita, JM Chia, KS Martos, C Jonasson, JG Colin, D Scelo, G Brennan, P TI A pooled analysis of second primary pancreatic cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE neoplasms, second primary; pancreatic neoplasms; risk factors ID LONG-TERM SURVIVORS; MALIGNANT NEOPLASMS; CERVICAL-CANCER; RISK-FACTORS; REPRODUCTIVE FACTORS; TESTICULAR CANCER; ADENOCARCINOMA; ENDOMETRIAL; REGISTRIES; CARCINOMA AB Studies of pancreatic cancer in the setting of second primary malignant neoplasms can provide etiologic clues. An international multicenter study was carried out using data from 13 cancer registries with a registration period up to year 2000. Cancer patients were followed up from the initial cancer diagnosis, and the occurrence of second primary malignant neoplasms was compared with expected values derived from local rates, adjusting for age, sex, and period of diagnosis. Results from individual registries were pooled by use of a fixed-effects model. People were at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancers of the pharynx, stomach, gallbladder, larynx, lung, cervix, corpus uteri, bladder, and eye and 10 years or later following a diagnosis of cancers of the stomach, colon, gallbladder, breast, cervix, placenta, corpus uteri, ovary, testis, bladder, kidney, and eye, as well as Hodgkin's and non-Hodgkin's lymphomas. Pancreatic cancer was connected with smoking-related cancers, confirming the etiologic role of tobacco. The associations with uterine and ovarian cancers suggest that reproductive factors might be implicated in pancreatic carcinogenesis. The elevated pancreatic cancer risk in young patients observed among several types of cancer implies a role of genetic factors. Radiotherapy is also suggested as a risk factor. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. Inst Populat Based Canc Res, Oslo, Norway. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. Karolinska Inst, Novum, Dept Biosci, Huddinge, Sweden. Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland. New S Wales Cent Canc Registry, Inst Canc, Eveleigh, NSW, Australia. Scottish Canc Registry, Informat Serv, Natl Hlth Serv, Edinburgh, Midlothian, Scotland. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Can Registry Slovenia, Inst Oncol, Ljubljana, Slovenia. CancerCare Manitoba, Epidemiol & Canc Registry, Winnipeg, MB, Canada. Univ Manitoba, Winnipeg, MB, Canada. Saskatchewan Canc Agcy, Regina, SK, Canada. Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. Singapore Canc Registry, Singapore, Singapore. Canc Registry Zaragoza, Hlth Dept Aragon Govt, Zaragoza, Spain. Univ Iceland, Fac Med, Reykjavik, Iceland. Iceland Canc Soc, Iceland Canc Registry, Reykjavik, Iceland. RP Shen, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI CHIA, Kee Seng/C-5790-2011; OI Olsen, Jorgen Helge/0000-0001-9633-5662; Brewster, David/0000-0002-5346-5608 NR 45 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2006 VL 163 IS 6 BP 502 EP 511 DI 10.1093/aje/kwj073 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 018NE UT WOS:000235770400002 PM 16421239 ER PT J AU Luo, S Wehr, NB Levine, RL AF Luo, S Wehr, NB Levine, RL TI Quantitation of protein on gels and blots by infrared fluorescence of Coornassie blue and Fast Green SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Coomassie blue; protein quantitation; infrared fluorescence; Fast Green ID COLI GLUTAMINE-SYNTHETASE AB Coomassie blue staining of gels and blots is commonly employed for detection and quantitation of proteins by densitometry. We found that Coomassie blue or Fast Green FCF bound to protein fluoresces in the near infrared. We took advantage of this property to develop a rapid and sensitive method for detection and quantitation of proteins in gels and oil blots. The fluorescence response is quantitative for protein content between 10 ng and 20 mu g per band or spot. Staining and destaining require only 30 min, and the method is compatible with subsequent immunodetection. Published by Elsevier Inc. C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, Bldg 10, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural NIH HHS NR 13 TC 55 Z9 57 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 15 PY 2006 VL 350 IS 2 BP 233 EP 238 DI 10.1016/j.ab.2005.10.048 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 023VT UT WOS:000236155000009 PM 16336940 ER PT J AU Neighbors, JD Salnikova, MS Beutler, JA Wiemer, DF AF Neighbors, JD Salnikova, MS Beutler, JA Wiemer, DF TI Synthesis and structure-activity studies of schweinfurthin B analogs: Evidence for the importance of a D-ring hydrogen bond donor in expression of differential cytotoxicity SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE schweinfurthin; stilbene; cytotoxic; 60-cell assay ID MACARANGA-SCHWEINFURTHII; METALATION; INHIBITORS; STILBENE; CANCER AB The synthesis and biological evaluation of several enantioenriched schweinfurthin B analogs were undertaken to develop structure-activity relationships and guide design of probes for their putative molecular target. The desired stilbenes contain a common left-half hexahydroxanthene ring system and an aromatic right-half with varied substituents. The synthesis involves penultimate Horner-Wadsworth-Emmons coupling of one of several right-half phosphonates with the aldehyde comprising the left-half of 3-deoxyschweinfurthin B. Preparation of the requisite phosphonates, and the respective stilbenes, as well as the cytotoxicity profiles of these new compounds in the National Cancer Institute's 60 cell-line anticancer screen is described. several of these analogs displayed cytotoxicity patterns well-correlated with the natural product and differences in activity of similar to 10(3) across the various cell lines. Together, these assay results indicate the importance of at least one free phenol group Oil the aromatic D-ring of this system for differential cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA. NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Wiemer, DF (reprint author), Univ Iowa, Dept Chem, Iowa City, IA 52242 USA. EM david-wiemer@uiowa.edu RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU Intramural NIH HHS; NCI NIH HHS [2 T32 CA79445-05] NR 25 TC 26 Z9 27 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 15 PY 2006 VL 14 IS 6 BP 1771 EP 1784 DI 10.1016/j.bmc.2005.10.025 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 015VS UT WOS:000235579900011 PM 16290161 ER PT J AU Lee, J Lee, JH Kim, SY Perry, NA Lewin, NE Ayres, JA Blumberg, PM AF Lee, J Lee, JH Kim, SY Perry, NA Lewin, NE Ayres, JA Blumberg, PM TI 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE protein kinase C; diacylglycerol; phorbol ester ID CONFORMATIONALLY CONSTRAINED ANALOGS; TUMOR PROMOTERS; PHORBOL ESTER; BINDING-AFFINITY; STRUCTURAL BASIS; DAG-LACTONES; DIACYLGLYCEROL; ACTIVATORS; PKC; COMPLEXITIES AB A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-alpha ligands. Among the analogues, 13c exhibited the most potent binding affinity with a K-i = 0.7 mu M. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study or 13c was carried out. (c) 2005 Elsevier Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. NCI, Ctr Canc Res, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr FU Intramural NIH HHS NR 20 TC 12 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 15 PY 2006 VL 14 IS 6 BP 2022 EP 2031 DI 10.1016/j.bmc.2005.10.051 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 015VS UT WOS:000235579900036 PM 16297629 ER PT J AU Kato, GJ McGcwan, V Machado, RF Little, JA Taylor, J Morris, CR Nichols, JS Wang, XD Poljakovic, M Morris, SM Gladwin, MT AF Kato, GJ McGcwan, V Machado, RF Little, JA Taylor, J Morris, CR Nichols, JS Wang, XD Poljakovic, M Morris, SM Gladwin, MT TI Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease SO BLOOD LA English DT Article ID ADHESION MOLECULE EXPRESSION; THALASSEMIA-INTERMEDIA; HEREDITARY SPHEROCYTOSIS; PLASMA HEMOGLOBIN; ENDOTHELIAL DYSFUNCTION; MEDIATED VASODILATION; VASOOCCLUSIVE CRISIS; HYDROXYUREA THERAPY; ARGININE METABOLISM; GENE-EXPRESSION AB Pulmonary hypertension is prevalent in adult patients with sickle cell disease and is strongly associated with early mortality and markers of hemolysis, in particular, serum lactate dehydrogenese (LDH). Intravascular hemolysis leads to impaired bioavailability of nitric oxide (NO), mediated by NO scavenging by plasma oxyhemoglobin and by arginine degradation by plasma arginase. We hypothesized that serum LDH may represent a convenient biomarker of intravascular hemolysis and NO bioavailability, characterizing a clinical subphenotype of hemolysis-associated vasculopathy. In a cohort of 213 patients with sickle cell disease, we found statistically significant associations of steady-state LDH with low levels of hemoglobin and haptoglobin and high levels of reticulocytes, bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase, and soluble adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels closely correlated with plasma cell-free hemoglobin, accelerated NO consumption by plasma, and impaired vasodilatory responses to an NO donor. Remarkably, this simple biomarker was associated with a clinical subphenotype of pulmonary hypertension, leg ulceration, priapism, and risk of death in patients with sickle cell disease. We propose that LDH elevation identifies patients with a syndrome of hemolysis-associated NO resistance, endothelial dysfunction, and end-organ vasculopathy. C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Childrens Hosp, Dept Emergency Med, Oakland, CA 94609 USA. Res Ctr, Oakland, CA USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. RP Kato, GJ (reprint author), NHLBI, Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10CRC,Rm 5-5140, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014; Morris, Sidney/I-3440-2015; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006012-01]; NCRR NIH HHS [M01-RR01271]; NHLBI NIH HHS [HL-04386-05]; NIGMS NIH HHS [R01 GM057384, R01 GM057384-07, R01 GM57384] NR 69 TC 263 Z9 279 U1 0 U2 21 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2006 VL 107 IS 6 BP 2279 EP 2285 DI 10.1182/blood-2005-06-2373 PG 7 WC Hematology SC Hematology GA 021VO UT WOS:000236014200017 PM 16291595 ER PT J AU Ahmadzadeh, M Rosenberg, ST AF Ahmadzadeh, M Rosenberg, ST TI IL-2 administration increases CD4(+)CD25(hi) Foxp3(+) regulatory T cells in cancer patients SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; PERIPHERAL-BLOOD; INTERLEUKIN-2; IMMUNITY; LYMPHOCYTES; INDUCTION; TOLERANCE; ANTIGEN; MEMORY; VIVO AB Interleukin-2 (IL-2) is historically known as a T-cell growth factor. Accumulating evidence from knockout mice suggests that IL-2 is crucial for the homeostasis and function of CD4(+)CD25(+) regulatory T cells in vivo. However, the impact of administered IL-2 in an immune intact host has not been studied in rodents or humans. Here, we studied the impact of IL-2 administration on the frequency and function of human CD4+CD2Ehi T cells in immune intact patients with melanoma or renal cancer. We found that the frequency of CD4(+)CD25(hi) T cells was significantly increased after IL-2 treatment, and these cells expressed phenotypic markers associated with regulatory T cells. In addition, both transcript and protein levels of Foxp3, a transcription factor exclusively expressed on regulatory T cells, were consistently increased in CD4 T cells following IL-2 treatment. Functional analysis of the increased number of CD4(+)CD25(hi) T cells revealed that this population exhibited potent suppressive activity in vitro. Collectively, our results demonstrate that administration of high-dose IL-2 increased the frequency of circulating CD4(+)CD25(hi) Foxp3(+) regulatory T cells. Our findings suggest that selective inhibition of IL-2-mediated enhancement of regulatory T cells may improve the therapeutic effectiveness of IL-2 administration. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, ST (reprint author), NCI, Surg Branch, NIH, CRC Bldg,Rm 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA142636] NR 26 TC 358 Z9 370 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2006 VL 107 IS 6 BP 2409 EP 2414 DI 10.1182/blood-2005-06-2399 PG 6 WC Hematology SC Hematology GA 021VO UT WOS:000236014200033 PM 16304057 ER PT J AU Lin, YW Nichols, RA Letterio, JJ Aplan, PD AF Lin, YW Nichols, RA Letterio, JJ Aplan, PD TI Notch1 mutations are important for leukemic transformation in murine models of precursor-T leukemia/lymphoma SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DOUBLE-TRANSGENIC MICE; SCL GENE-PRODUCT; CELL MALIGNANCIES; LMO1; EXPRESSION; DIFFERENTIATION; INSTABILITY; PATHWAY; ALTER AB NOTCH1 is frequently mutated in human precursor T-cell lymphoblastic leukemia/ lymphoma (pre-T LBL). In the current study, we found that 13 of 19 cell lines and 29 of 49 primary tumors from SCL/LMO1, OLIG2/LMO1, OLIG2, LMO1, NUP98/ HOXD13, and p27(-/-)/SMAD3(+/-) mice had Notch1 mutations in either the heterodimerization (HD) or the glutamic acid/serine/threonine (PEST) domain but not both. Thymocytes from clinically healthy SCL/LMO1 mice aged 5 weeks did not have Notch1 mutations, whereas thymocytes from clinically healthy SCL/LMO1 mice aged 8 to 12 weeks did have Notch1 mutations and formed tumors upon transplantation into nude mice. Remarkably, all of the HD domain mutations that we identified were single-base substitutions, whereas all of the PEST domain mutations were insertions or deletions, half of which mapped to 1 of 2 mutational "hot spots." Taken together, these findings indicate that Notch1 mutations are very frequent events that are acquired relatively early in the process of leukemic transformation and are important for leukemic cell growth. C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20889 USA. NCI, Lab Cell Regulat & Carcinogenesis, Canc Res Ctr, NIH, Bethesda, MD USA. RP Aplan, PD (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU Intramural NIH HHS NR 23 TC 83 Z9 86 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2006 VL 107 IS 6 BP 2540 EP 2543 DI 10.1182/blood-2005-07-3013 PG 4 WC Hematology SC Hematology GA 021VO UT WOS:000236014200052 PM 16282337 ER PT J AU Anderson, JM Oliveira, F Kamhawi, S Mans, BJ Reynoso, D Seitz, AE Lawyer, P Garfield, M Pham, MV Valenzuela, JG AF Anderson, JM Oliveira, F Kamhawi, S Mans, BJ Reynoso, D Seitz, AE Lawyer, P Garfield, M Pham, MV Valenzuela, JG TI Comparative salivary gland transcriptomics of sandfly vectors of visceral leishmaniasis SO BMC GENOMICS LA English DT Article ID FLY LUTZOMYIA-LONGIPALPIS; MOSQUITO AEDES-AEGYPTI; FEMALE MOSQUITO; PHLEBOTOMINE SANDFLIES; ANOPHELES-GAMBIAE; SECRETED PROTEINS; VENOM ALLERGEN; CDNA CLONING; FAMILY; SEQUENCE AB Background: Immune responses to sandfly saliva have been shown to protect animals against Leishmania infection. Yet very little is known about the molecular characteristics of salivary proteins from different sandflies, particularly from vectors transmitting visceral leishmaniasis, the fatal form of the disease. Further knowledge of the repertoire of these salivary proteins will give us insights into the molecular evolution of these proteins and will help us select relevant antigens for the development of a vector based anti-Leishmania vaccine. Results: Two salivary gland cDNA libraries from female sandflies Phlebotomus argentipes and P. perniciosus were constructed, sequenced and proteomic analysis of the salivary proteins was performed. The majority of the sequenced transcripts from the two cDNA libraries coded for secreted proteins. In this analysis we identified transcripts coding for protein families not previously described in sandflies. A comparative sandfly salivary transcriptome analysis was performed by using these two cDNA libraries and two other sandfly salivary gland cDNA libraries from P. ariasi and Lutzomyia longipalpis, also vectors of visceral leishmaniasis. Full-length secreted proteins from each sandfly library were compared using a stand-alone version of BLAST, creating formatted protein databases of each sandfly library. Related groups of proteins from each sandfly species were combined into defined families of proteins. With this comparison, we identified families of salivary proteins common among all of the sandflies studied, proteins to be genus specific and proteins that appear to be species specific. The common proteins included apyrase, yellow-related protein, antigen-5, PpSP15 and PpSP32-related protein, a 33-kDa protein, D7-related protein, a 39- and a 16.1-kDa protein and an endonuclease-like protein. Some of these families contained multiple members, including PPSP15-like, yellow proteins and D7-related proteins suggesting gene expansion in these proteins. Conclusion: This comprehensive analysis allows us the identification of genus-specific proteins, species-specific proteins and, more importantly, proteins common among these different sandflies. These results give us insights into the repertoire of salivary proteins that are potential candidates for a vector-based vaccine. C1 NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Fed Bahia, Fundacao Oswaldo Cruz, Ctr Pesquisa Goncalo Moniz, Salvador, BA, Brazil. Univ Fed Bahia, Fac Med, Salvador, BA, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Vector Biol Sect, LMVF, NIH, Rockville, MD USA. NIAID, Res Technol Branch, Rockville, MD USA. RP Valenzuela, JG (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. EM jenanderson@niaid.nih.gov; loliveira@niaid.nih.gov; skamhawi@niaid.nih.gov; bmans@niaid.nih.gov; David.reynoso@uth.tmc.edu; aeseitz@gmail.com; plawyer@niaid.nih.gov; mgarfield@niaid.nih.gov; vapham@niaid.nih.gov; jvalenzuela@niaid.nih.gov RI Oliveira, Fabiano/B-4251-2009; OI Oliveira, Fabiano/0000-0002-7924-8038; Mans, Ben/0000-0002-0177-0029 FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI000932] NR 54 TC 88 Z9 90 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 15 PY 2006 VL 7 AR 52 DI 10.1186/1471-2164-7-52 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 031NV UT WOS:000236712200001 PM 16539713 ER PT J AU Del Parigi, A Panza, F Capurso, C Solfrizzi, V AF Del Parigi, A Panza, F Capurso, C Solfrizzi, V TI Nutritional factors, cognitive decline, and dementia SO BRAIN RESEARCH BULLETIN LA English DT Review DE malnutrition; dementia; cognitive functions; micronutrients; macronutrients ID INCIDENT ALZHEIMER-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; NEURONAL SIGNAL-TRANSDUCTION; ELEVATED PLASMA HOMOCYSTEINE; VITAMIN-E SUPPLEMENTATION; MENTAL-STATE-EXAMINATION; 3RD NATIONAL-HEALTH; AGED GARLIC EXTRACT; ELDERLY-PEOPLE; VASCULAR DEMENTIA AB Nutritional factors and nutritional deficiencies have been repeatedly associated with cognitive impairment. Most of the evidence is based on cross-sectional studies, which cannot prove whether a nutritional deficit is the cause or the consequence of an impaired cognitive status. In fact, cognitive impairment, in turn, can determine changes in dietary habits and consequent nutritional deficiencies. We reviewed clinical and epidemiological studies from January 1983 to June 2004. Several cross-sectional and fewer prospective studies reported an association between dietary or supplemental intake of antioxidants and protection from cognitive decline and dementia. There are negative reports as well and some methodological biases might have affected the consistencies across studies. Deficiencies of several B vitamins have been associated with cognitive dysfunction in many observational studies. More recently, deficiencies of folate (139) and cobalamine (1312) have been studied in relation to hyperhomocysteinemia as potential determinants of cognitive impairment, dementia, and Alzheimer's disease (AD). A small number of studies assessed the association between intake of macronutrients and cognitive function or dementia. Among the others, the intake of fatty acids and cholesterol has received particular attention. Although the results are not always consistent, most studies have reported a protective role of dietary intakes of poly- and mono-unsaturated fatty acids against cognitive decline and AD. We point out that well designed intervention studies are warranted in order to establish specific levels of micro- and macronutrient deficiencies and to set general recommendations for the population. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDDKD, NIH, Obes & Diabet Clin Res Sect, Phoenix, AZ 85016 USA. Univ Bari, Dept Geriatr, Ctr Aging Brain, Memory Unit, Bari, Italy. Univ Foggia, Dept Geriatr, Foggia, Italy. RP Del Parigi, A (reprint author), NIDDKD, NIH, Obes & Diabet Clin Res Sect, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM angelo.delparigi@pfizer.com OI Capurso, Cristiano/0000-0002-1152-3371; Panza, Francesco/0000-0002-7220-0656 NR 197 TC 45 Z9 47 U1 7 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAR 15 PY 2006 VL 69 IS 1 BP 1 EP 19 DI 10.1016/j.brainresbull.2005.09.020 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 015XT UT WOS:000235585500001 PM 16464680 ER PT J AU Bolen, S Tilburt, J Baffi, C Gary, TL Powe, N Howerton, M Ford, J Lai, G Wilson, R Bass, E AF Bolen, S Tilburt, J Baffi, C Gary, TL Powe, N Howerton, M Ford, J Lai, G Wilson, R Bass, E TI Defining "Success" in recruitment of underrepresented populations to cancer clinical trials - Moving toward a more consistent approach SO CANCER LA English DT Editorial Material DE underrepresented; underserved; cancer; clinical trials; recruitment; accrual; minority ID AFRICAN-AMERICANS; PREVENTION TRIAL; ONCOLOGY PROGRAM; OLDER PATIENTS; BREAST-CANCER; PARTICIPATION; ENROLLMENT; WOMEN; AGE; REPRESENTATION AB Although medically underserved groups bear a heavy burden of cancer disease and governmental agencies have required inclusion of minorities and women in cancer clinical trials since 1993, many of these groups are underrepresented in cancer prevention or treatment clinical trials. To assess and enhance recruitment of underrepresented populations into cancer-related clinical trials, investigators and governmental agencies need consistent measurement approaches for recruitment that can be applied to diverse settings where trials are conducted. We conducted a systematic review to evaluate what measurement approaches were used to evaluate the success of recruitment of underrepresented groups into cancer prevention or treatment trials, and whether these recruitment goals were stated a priori. Only two articles reported an a priori recruitment goal. The recruitment measurement approaches varied considerably, with no consistent standard, especially for individual trials. By using the empiric evidence from this review in conjunction with the National Institutes of Health (NIH) guidelines, we constructed a framework for choosing consistent a priori recruitment goals for underrepresented groups based on the research question and study location. Using consistent measurement approaches for underrepresented groups will improve comparability of recruitment strategies across trials, improve equity in distribution of benefits and burdens of cancer-related clinical trials, and may improve applicability of trial results to multiple populations. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD USA. NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Bolen, S (reprint author), 8508 16th St,Apt 222, Silver Spring, MD 20910 USA. EM sgolden4@jhmi.edu NR 47 TC 28 Z9 28 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2006 VL 106 IS 6 BP 1197 EP 1204 DI 10.1002/cncr.21745 PG 8 WC Oncology SC Oncology GA 021XP UT WOS:000236019500001 PM 16453333 ER PT J AU Balkwill, FR Ashworth, A Bast, RC Berek, JS Boyd, J Disis, ML Gabra, H Gore, ME Hamilton, TC Jacobs, IJ Kaye, SB Kohn, EC Mills, GB Urban, ND AF Balkwill, FR Ashworth, A Bast, RC Berek, JS Boyd, J Disis, ML Gabra, H Gore, ME Hamilton, TC Jacobs, IJ Kaye, SB Kohn, EC Mills, GB Urban, ND TI 10th Biennial Helene Harris Memorial Trust Meeting SO CANCER RESEARCH LA English DT Article C1 Barts & London Queen Marys Sch Med & Dent, London, England. Univ London Imperial Coll Sci Technol & Med, Dept Canc Med, Sect Mol Therapeut, London SW7 2AZ, England. UCL, Dept Gynecol Oncol, London, England. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. Univ Calif Los Angeles, Div Gynecol Oncol, Los Angeles, CA USA. Fox Chase Canc Ctr, Dept Surg & Med, Philadelphia, PA 19111 USA. Univ Washington, Med Ctr, Div Oncol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Gynecol Canc Res Programme, Seattle, WA 98104 USA. NCI, Pathol Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. RP Balkwill, FR (reprint author), Barts & London Queen Marys Sch Med & Dent, London, England. RI Bast, Robert/E-6585-2011; OI Bast, Robert/0000-0003-4621-8462; Balkwill, Frances/0000-0002-5587-9759 FU Medical Research Council [G0501974] NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 2904 EP 2906 DI 10.1158/0008-5472.CAN-05-2093 PG 3 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500005 PM 16540635 ER PT J AU Dudgeon, C Kek, C Demidov, ON Saito, S Fernandes, K Diot, A Bourdon, JC Lane, DP Appella, E Fornace, AJ Bulavin, DV AF Dudgeon, C Kek, C Demidov, ON Saito, S Fernandes, K Diot, A Bourdon, JC Lane, DP Appella, E Fornace, AJ Bulavin, DV TI Tumor susceptibility and apoptosis defect in a mouse strain expressing a human p53 transgene SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER CELLS; KNOCK-IN MICE; DNA-DAMAGE; MUTATIONS; MDM2; PUMA; VIVO; PHOSPHORYLATION; TUMORIGENESIS; ACTIVATION AB Activation of apoptosis is believed to be critical for the role of p53 as a tumor suppressor. Here, we report a new mouse strain carrying a human p53 transgene in the mouse p53-null background. Expression of human p53 in these mice was comparable with wild-type murine p53; however, transactivation, induction of apoptosis, and G(1)-S checkpoint, but not transrepression or regulation of a centrosomal checkpoint, were deregulated. Although multiple functions of p53 were abrogated, mice carrying the human p53 transgene did not show early onset of tumors as typically seen for p53-null mice. In contrast, human p53 in the p53-null background did not prevent accelerated tumor development after genotoxic or oncogenic stress. Such behavior of human p53 expressed at physiologic levels in transgenic cells could be explained by unexpectedly high binding with Mdm2. By using Nutlin-3a, an inhibitor of the interaction between Mdm2 and p53, we were able to partially reconstitute p53 transactivation and apoptosis in transgenic cells. Our findings indicate that the interaction between p53 and Mdm2 controls p53 transcriptional activity in homeostatic tissues and regulates DNA damage- and oncogene-induced, but not spontaneous, tumorigenesis. C1 Inst Mol & Cell Biol, Singapore 138673, Singapore. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Dundee, Dept Surg, Canc Res UK Cell Transformat Res Grp, Dundee, Scotland. Univ Dundee, Dept Mol Oncol, Canc Res UK Cell Transformat Res Grp, Dundee, Scotland. RP Dudgeon, C (reprint author), Inst Mol & Cell Biol, 61 Biopolis Dr, Singapore 138673, Singapore. EM dvbulavin@imcb.a-star.edu.sg; afornace@hsph.harvard.edu RI bourdon, jean-christophe/A-4439-2008; Fornace, Albert/A-7407-2008; Lane, David/C-4920-2008; ASTAR, IMCB/E-2320-2012; OI Fornace, Albert/0000-0001-9695-085X; Bourdon, jean-christophe/0000-0003-4623-9386; Demidov, Oleg/0000-0003-4323-7174 FU Intramural NIH HHS NR 42 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 2928 EP 2936 DI 10.1158/0008-5472.CAN-05-2063 PG 9 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500010 PM 16540640 ER PT J AU Basil, CF Zhao, YD Zavaglia, K Jin, P Panelli, MC Voiculescu, S Mandruzzato, S Lee, HM Seliger, B Freedman, RS Taylor, PR Hu, N Zanovello, P Marincola, FM Wang, E AF Basil, CF Zhao, YD Zavaglia, K Jin, P Panelli, MC Voiculescu, S Mandruzzato, S Lee, HM Seliger, B Freedman, RS Taylor, PR Hu, N Zanovello, P Marincola, FM Wang, E TI Common cancer biomarkers SO CANCER RESEARCH LA English DT Article ID MESSENGER-RNA AMPLIFICATION; PROSTATE-SPECIFIC ANTIGEN; GENE-EXPRESSION DATA; CELL-LINES; OVARIAN-CANCER; SYSTEMATIC VARIATION; COLORECTAL-CANCER; MELANOMA PATIENTS; RT-PCR; CARCINOMA AB There is an increasing interest in complementing conventional histopathologic evaluation with molecular tools that could increase the sensitivity and specificity of cancer staging for diagnostic and prognostic purposes. This study strove to identify cancer-specific markers for the molecular detection of a broad range of cancer types. We used 373 archival samples inclusive of normal tissues of various lineages and benign or malignant tumors (predominantly colon, melanoma, ovarian, and esophageal cancers). All samples were processed identically and cohybridized with an identical reference RNA source to a custom-made cDNA array platform. The database was split into training (n = 201) and comparable prediction (n = 172) sets. Leave-one-out cross-validation and gene pairing analysis identified putative cancer biomarkers overexpressed by malignant lesions independent of tissue of derivation. In particular, seven gene pairs were identified with high predictive power (87%) in segregating malignant from benign lesions. Receiver operator characteristic curves based on the same genes could segregate malignant from benign tissues with 94% accuracy. The relevance of this study rests on the identification of a restricted number of biomarkers ubiquitously expressed by cancers of distinct histology. This has not been done before. These biomarkers could be used broadly to increase the sensitivity and accuracy of cancer staging and early detection of locoregional or systemic recurrence. Their selective expression by cancerous compared with paired normal tissues suggests an association with the oncogenic process resulting in stable expression during disease progression when the presently used differentiation markers are unreliable. C1 NCI, Dept Transfus Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Padua, Dept Oncol & Surg Sci, Oncol Sect, Padua, Italy. Boston Strateg Patterns, Boston, MA USA. Univ Halle Wittenberg, Inst Med Immunol, Halle, Germany. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol & Obstet, Houston, TX 77030 USA. Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Wang, E (reprint author), NCI, Dept Transfus Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1N224B,10 Ctr Dr, Bethesda, MD 20892 USA. EM ewang@cc.nih.gov OI MANDRUZZATO, SUSANNA/0000-0002-0707-995X NR 55 TC 59 Z9 63 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 2953 EP 2961 DI 10.1158/0008-5472.CAN-05-3433 PG 9 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500013 PM 16540643 ER PT J AU Artym, VV Zhang, Y Seillier-Moiseiwitsch, FO Yamada, KM Mueller, SC AF Artym, VV Zhang, Y Seillier-Moiseiwitsch, FO Yamada, KM Mueller, SC TI Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: Defining the stages of invadopodia formation and function SO CANCER RESEARCH LA English DT Article ID PP60C-SRC PROTEIN-KINASE; TUMOR CELL-LINES; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; TYROSINE PHOSPHORYLATION; INVASIVE CELLS; SURFACE; DEGRADATION; ACTIVATION; MOTILITY AB Metastatic tumor cells that actively migrate and invade surrounding tissues rely on invadopodia to degrade extracellular matrix (ECM) barriers. Invadopodia are membrane protrusions that localize enzymes required for ECM degradation. Little is known about the formation, function, and regulation of invadopodia. Here, we show that invadopodia have two distinct aspects: (a) structural for organizing the cellular actin cytoskeleton to form membrane protrusions and (b) functional for using proteolytic enzyme(s) for ECM degradation. Small interfering RNA (siRNA) inhibition established that organization of invadopodia structure requires cortactin, whereas protease inhibitor studies identified membrane type I matrix metalloproteinase (MT1-MMP) as the key invadopodial enzyme responsible for gelatin matrix degradation in the breast carcinoma cell line MDA-MB-231. The inhibition of invadopodial structure assembly by cortactin depletion resulted in a block of matrix degradation due to failure of invadopodia formation. Either protease inhibition or MT1-MMP siRNA depletion moderately decreased the formation of invadopodial structures that were identified as actin-cortactin accumulations at the ventral cell membrane adherent to matrix. The invadopodia that were able to form upon MT1-MMP inhibition or depletion retained actin-cortactin accumulations but were unable to degrade matrix. Examination of cells at different time points as well as live-cell imaging revealed four distinct invadopodial stages: membrane cortactin aggregation at membranes adherent to matrix, MT1-MMP accumulation at the region of cortactin accumulation, matrix degradation at the invadopodia region, and subsequent cortactin dissociation from the area of continued MT1-MMP accumulation associated with foci of degraded matrix. Based on these results, we propose a stepwise model of invadopodia formation and function. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Sch Med, Washington, DC 20057 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Div Biostat & Bioinformat, Sch Med, Washington, DC 20057 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Mueller, SC (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Sch Med, E301 Res Bldg,Box 571469, Washington, DC 20057 USA. EM muellers@georgetown.edu OI Yamada, Kenneth/0000-0003-1512-6805 NR 46 TC 306 Z9 312 U1 3 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 3034 EP 3043 DI 10.1158/0008-5472.CAN-05-2177 PG 10 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500022 PM 16540652 ER PT J AU Somasundaram, R Swoboda, R Caputo, L Otvos, L Weber, B Volpe, P van Belle, P Hotz, S Elder, DE Marincola, FM Schuchter, L Guerry, D Czerniecki, BJ Herlyn, D AF Somasundaram, R Swoboda, R Caputo, L Otvos, L Weber, B Volpe, P van Belle, P Hotz, S Elder, DE Marincola, FM Schuchter, L Guerry, D Czerniecki, BJ Herlyn, D TI Human leukocyte antigen-A2-restricted CTL responses to mutated BRAF peptides in melanoma patients SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; T-CELL; TUMOR-ANTIGENS; HIGH-FREQUENCY; RAS MUTATIONS; COLON-CANCER; PROGRESSION; ANTIBODY; IMMUNITY; CD4(+) AB Mutated BRAF (BRAF(V600E)) is a potential immunotherapeutic target for melanoma because of its tumor specificity and expression in the majority of these lesions derived from different patients. BRAF(V600E) is expressed intracellularly and not on the cell surface, therefore providing a target for T cells but not B cells. Demonstration of patients' T cell responses to BRAF(V600E) would suggest the feasibility of active specific immunotherapy targeting the mutation in these patients. In the present study, BRAF(V600E) peptides with putative binding sites for human leukocyte antigen (HLA)-A2 were used to stimulate T lymphocytes of HLA-A2-positive melanoma patients. Four of five patients with BRAF(V600E)-positive lesions showed lymphoproliferative responses to BRAF(V600E) peptide stimulation. These responses were specific for the mutated epitope and HLA-A2 was restricted in three patients. Lymphocytes from these three patients were cytotoxic against HLA-A2-matched BRAF(V600E)-positive melanoma cells. None of the four patients with BRAF(V600E)-negative lesions and none of five healthy donors had lymphoproliferative responses specific for the mutated epitope. The high prevalence (similar to 50%) of HLA-A2 among melanoma patients renders HLA-A2-restricted BRAF(V600E) peptides attractive candidate vaccines for these patients. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Melanoma Program, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Div Hematol Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Surg, Div Surg Oncol, Philadelphia, PA 19104 USA. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Herlyn, D (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM dherlyn@wistar.org FU NCI NIH HHS [CA10815, CA25874, CA93372] NR 32 TC 22 Z9 23 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2006 VL 66 IS 6 BP 3287 EP 3293 DI 10.1158/0008-5472.CAN-05-1932 PG 7 WC Oncology SC Oncology GA 022ZA UT WOS:000236093500052 PM 16540682 ER PT J AU Mayburd, AL Martinez, A Sackett, D Liu, HT Shih, J Tauler, J Avis, I Mulshine, JL AF Mayburd, AL Martinez, A Sackett, D Liu, HT Shih, J Tauler, J Avis, I Mulshine, JL TI Ingenuity network-assisted transcription profiling: Identification of a new pharmacologic mechanism for MK886 SO CLINICAL CANCER RESEARCH LA English DT Article ID 5-LIPOXYGENASE-ACTIVATING PROTEIN; INHIBITOR MK886; LEUKEMIA CELLS; LUNG-CANCER; ACID; APOPTOSIS; CYCLOOXYGENASE; ACTIVATION; GROWTH; CARCINOGENESIS AB The small molecular inhibitor MK886 is known to block 5 - lipoxygenase-activating protein ALOX5AP and shows antitumor activity in multiple human cell lines. The broad antitumor therapeutic window reported in vivo for MK886 in rodents supports further consideration of this structural class. Better understanding of the mode of action of the drug is important for application in humans to take place. Affymetrix microarray study was conducted to explore MK886 pharmacologic mechanism. Ingenuity Pathway Analysis software was applied to validate the results at the transcriptional level by putting them in the context of an experimental proteomic network. Genes most affected by MK886 included actin B and focal adhesion components. A subsequent National Cancer Institute-60 panel study, RT-PCR validation followed by confocal microscopy, and Western blotting also pointed to actin B down-regulation, filamentous actin loss, and disorganization of the transcription machinery. In agreement with these observations, MK886 was found to enhance the effect of UV radiation in H720 lung cancer cell line. In light of the modification of cytoskeleton and cell motility by lipid phosphoinositide 3-kinase products, MK886 interaction with actin B might be biologically important. The low toxicity of MK886 in vivo was modeled and explained by binding and transport by dietary lipids. The rate of lipid absorbance is generally higher for tumors, suggesting a promise of a targeted liposome-based delivery system for this drug. These results suggest a novel antitumor pharmacologic mechanism. C1 NCI, Intervent Sect, NIH, Bethesda, MD 20859 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Consejo Super Invest Cient, Inst Cajal, Dept Cell Biol & Neuroanat, Madrid, Spain. Sci Applicat Int Corp, Ctr Bioinformat, Rockville, MD USA. NCI, Biometr Res Branch, NIH, Rockville, MD USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Mayburd, AL (reprint author), NCI, Intervent Sect, NIH, Bethesda, MD 20859 USA. EM mayburna@mail.nih.gov RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 FU Intramural NIH HHS NR 35 TC 57 Z9 61 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2006 VL 12 IS 6 BP 1820 EP 1827 DI 10.1158/1078-0432.CCR-05-2149 PG 8 WC Oncology SC Oncology GA 028AX UT WOS:000236458800024 PM 16551867 ER PT J AU Gelbard, A Garnett, CT Abrams, SI Patel, V Gutkind, JS Palena, C Tsang, KY Schlom, J Hodge, JW AF Gelbard, A Garnett, CT Abrams, SI Patel, V Gutkind, JS Palena, C Tsang, KY Schlom, J Hodge, JW TI Combination chemotherapy and radiation of human squamous cell carcinoma of the head and neck augments CTL-mediated lysis SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; HUMAN CARCINOEMBRYONIC ANTIGEN; ADVANCED LARYNGEAL-CANCER; TUMOR-CELLS; RECOMBINANT VACCINIA; GENE-EXPRESSION; LYTIC PATHWAYS; TARGET-CELLS; FOLINIC ACID; KILLER-CELLS AB Purpose: The combination of systemic multiagent chemotherapy (5-fluorouracil + cisplatin) and tumor irradiation is standard of care for head and neck squamous cell carcinoma (HNSCC). Furthermore, it has been shown that sublethal doses of radiation or chemotherapeutic drugs in diverse cancer types may alter the phenotype or biology of neoplastic cells, making them more susceptible to CTL-mediated cytotoxicity. However, little is known about the potential synergistic effect of drug plus radiation on CTL killing. Here, we examined whether the combination of two chemotherapeutics and ionizing radiation enhanced CTL-mediated destruction of HNSCC more so than either modality separately, as well as the basis for the enhanced tumor cell lysis. Experimental Design: Several HNSCC cell lines with distinct biological features were treated with sublethal doses of cisplatin and 5-fluorouracil for 24 hours and with 10-Gy irradiation. Seventy-two hours postirradiation, tumor cells were exposed to an antigen-specific CD8(+) CTL directed against carcinoembryonic antigen or MUC-1. Results: In three of three tumor cell lines tested, enhanced CTL activity was observed when the two modalities (chemotherapy and radiation) were combined as compared with target cells exposed to either modality separately. CTL-mediated lysis was MHC restricted and antigen specific and occurred almost entirely via the perforin pathway. Moreover, the combination treatment regimen led to a 50% reduction in Bcl-2 expression whereas single modality treatment had little bearing on the expression of this antiapoptotic gene. Conclusions: Overall, these results reveal that (a) CTL killing can be enhanced by combining multiagent chemotherapy and radiation and (b) combination treatment enhanced or sensitized HNSCC to the perforin pathway, perhaps by down-regulating Bcl-2 expression. These studies thus form the rational basis for clinical trials of immunotherapy concomitant with the current standard of care of HNSCC. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Room 8B09,Bldg 10,10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural NIH HHS [Z99 CA999999] NR 59 TC 51 Z9 52 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2006 VL 12 IS 6 BP 1897 EP 1905 DI 10.1158/1078-0432.CCR-05-1761 PG 9 WC Oncology SC Oncology GA 028AX UT WOS:000236458800032 PM 16551875 ER PT J AU Chu, JH Feudtner, C Heydon, K Walsh, TJ Zaoutis, TE AF Chu, JH Feudtner, C Heydon, K Walsh, TJ Zaoutis, TE TI Hospitalizations for endemic mycoses: A population-based national study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COCCIDIOIDOMYCOSIS; BLASTOMYCOSIS; ARIZONA AB We performed a retrospective cohort study, using the 2002 Nationwide Inpatient Sample, a national database of hospital inpatient stays, to describe the incidence and epidemiology of endemic mycoses requiring hospitalization. An estimated 332 pediatric and 6003 adult patients with endemic mycoses required hospitalization (4.6 and 28.7 cases per 1 million children and adults, respectively). Crude mortality rates were 5% and 7% among children and adults, respectively. C1 Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Pediat Generalist Res Grp, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Gen Pediat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD USA. RP Zaoutis, TE (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, 3535 Market St,Rm 1527, Philadelphia, PA 19104 USA. EM zaoutis@email.chop.edu FU AHRQ HHS [K08 HS00002]; NIAID NIH HHS [AI-0629753] NR 12 TC 89 Z9 92 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2006 VL 42 IS 6 BP 822 EP 825 DI 10.1086/500405 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 012HW UT WOS:000235330200015 PM 16477560 ER PT J AU Das, B Cai, LQ Carter, MG Piao, YL Sharov, AA Ko, MSH Brown, DD AF Das, B Cai, LQ Carter, MG Piao, YL Sharov, AA Ko, MSH Brown, DD TI Gene expression changes at metamorphosis induced by thyroid hormone in Xenopus laevis tadpoles SO DEVELOPMENTAL BIOLOGY LA English DT Article DE thyroid hormone; metamorphosis; tadpole; Xenopus laevis; tail resorption; limb growth; brain ventricle proliferation; mitochondrial electron transport chain; cell cycle; transcriptional regulation ID INDUCED TAIL RESORPTION; AMPHIBIAN METAMORPHOSIS; SIGNAL-TRANSDUCTION; PROGRAMS; GROWTH; DEIODINASE; SURVIVAL; RECEPTOR; DEATH; LIMB AB Thyroid hormone (TH) controlled gene expression profile shave been studied in the tail, hind limb and brain tissues during TH-induced and spontaneous Xenopus laevis metamorphosis. Amplified cRNA probes mixed with a universal standard were hybridized to a set of 21,807 strand 60-mer oligonucleotides on each slide representing the entries in X laevis UniGene Build 48. Most of the up-regulated genes in hind limb and brain are the same. This reflects in part the fact that the initial response to TH induction in both tissues is cell proliferation. A large number of up-regulated genes in the limb and brain programs encode common components of the cell cycle, DNA and RNA metabolism, transcription and translation. Notch is one of the few genes that is differentially expressed exclusively in the brain in the first 48 h of TH induction studied in these experiments. The TH-induced gene expression changes in the tail are different from the limb and brain programs. Distinct muscle and fibroblast programs were identified in the tail. Dying muscle fibers in tail (marked by active caspase-3) up-regulate a group of genes that include proteolytic enzymes. At the climax of metamorphosis, tail muscle down-regulates more than half of the genes that encode the glycolytic enzymes in the cytoplasm and the tricarboxylic acid pathway and all five complexes of the electron transport system in mitochondria. These changes in gene expression precede the activation of caspase-3. Some of these same energy metabolism-retated genes are up-regulated in the limb and brain programs by TH. A prominent feature of the tail fibroblasts is the down-regulation of several collagen and other extra cellular matrix genes and the up-regulation of hydrolytic enzymes that are responsible for dissolving the notochord and resorbing the tail. (C) 2005 Elsevier Inc. All rights reserved. C1 Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21218 USA. NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Brown, DD (reprint author), Carnegie Inst Washington, Dept Embryol, 3520 San Martin Dr, Baltimore, MD 21218 USA. EM brown@ciwemb.edu RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009; OI Ko, Minoru/0000-0002-3530-3015; Cai, Liquan/0000-0001-9192-2673 FU Intramural NIH HHS NR 41 TC 70 Z9 73 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2006 VL 291 IS 2 BP 342 EP 355 DI 10.1016/j.ydbio.2005.12.032 PG 14 WC Developmental Biology SC Developmental Biology GA 027JF UT WOS:000236410900014 PM 16458881 ER PT J AU Nelson, RA Boyd, SJ Ziegelstein, RC Herning, R Cadet, JL Henningfield, JE Schuster, CR Contoreggi, C Gorelick, DA AF Nelson, RA Boyd, SJ Ziegelstein, RC Herning, R Cadet, JL Henningfield, JE Schuster, CR Contoreggi, C Gorelick, DA TI Effect of rate of administration on subjective and physiologica effects of intravenous cocaine in humans SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; infusion rate; cardiovascular; subjective ID INJECTION SPEED; ABUSE LIABILITY; RHESUS-MONKEYS; DURATION; REINFORCEMENT; SENSITIZATION; COMBINATION; DIAZEPAM; INFUSION AB The rate hypothesis of psychoactive drug action holds that the faster a drug reaches the brain and starts to act, the greater its reinforcing effects and abuse liability. A previous human study using a single cocaine dose confirmed the rate hypothesis for subjective responses, but found no rate effect on cardiovascular responses. We evaluated the rate hypothesis in 17 experienced cocaine users (7 [all men] provided complete data; 6 participated in only 1-2 sessions) by administering IV cocaine at each of three closes (10, 25, 50 mg) and injection durations (10, 30, 60 s) in a double-blind, placebo-controlled, escalating dose design. Heart rate, blood pressure, and Positive (e.g., rush, high) and negative (e.g., feel bad, anxious) Subjective effects (100-mm visual analogue scales) were measured for I It after dosing. Peak change from baseline, time to peak, and area under the time-response curve were evaluated with repeated measures mixed linear regression analyses, allowing use of data from all sessions for all subjects, including non-completers. Both close (mg) and infusion rate (mg/s) significantly influenced most subjective and cardiovascular variables. Analysis of the interaction suggested that dose had a stronger impact than rate. Rate had a stronger influence on positive subjective effects than on negative Subjective effects or cardiovascular variables. These findings provide Support for the rate hypothesis as it applies to both subjective and cardiovascular effects of IV cocaine administration in humans. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21224 USA. Pinney Associates, Bethesda, MD 20814 USA. Wayne State Univ, Sch Med, Dept Psychiat, Detroit, MI 48207 USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS NR 27 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 15 PY 2006 VL 82 IS 1 BP 19 EP 24 DI 10.1016/j.drugalcdep.2005.08.004 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 025BA UT WOS:000236239100003 PM 16144747 ER PT J AU Compton, P Ling, W Moody, D Chiang, N AF Compton, P Ling, W Moody, D Chiang, N TI Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE buprenorphine; bioavailability; pharmacokinetics ID RELATIVE BIOAVAILABILITY; OPIATE DEPENDENCE; METHADONE; FORMULATIONS; NALOXONE AB Aims: Two tablet formulations of buprenorphine (a buprenorphine mono-product, subutex(R), and a buprenorphine/naloxone combination product, Suboxone(R)) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liquid preparation. To assist the clinician in interpreting the relevant literature in establishing dosing parameters for prescription of tablet buprenorphine, this Study was designed to compare the steady state: (1) pharmacokinetics and bioavailability, and (2) physiological, subjective and objective opiate effects of two 8 mg buprenorphine tablets (16 mg) to those of 1 ml (8 mg/ml) buprenorphine solution based upon early reports Suggesting that the bioavailability of the tablet was approximately 50% of that of the liquid. Design: Randomized, open-label, two-way crossover Study. Setting: Inpatient hospitalization for 21 days. Participants: Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence. Intervention: Subjects received one of the two buprenorphine formulations in the first 10-day period, and the other for the second 10-day period with no washout. Measurements: Pharmacokinetic analyses, opiate effects and adverse events. Findings: Drug steady state was reached by Day 7 of each 10-day period, area under the Curve for 16 mg (two 8 mg) tablets was higher than the solution. The only non-kinetic statistically significant difference observed between the formulations was in changes in total opioid agonist score. Conclusions: The serum concentration achieved by 16 mg of tablet buprenorphine is higher than that of the 8 mg Solution, although differences between physiologic, subjective and objective opioid effects were not noted. The relative bioavailability of tablet versus solution is estimated to be 0.71; thus, with respect to dosing parameters for the tablet, clinicians should consider using less than 16 mg to achieve bioequivalence to the 8 mg solution. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90095 USA. Univ Utah, Ctr Human Toxicol, Salt Lake City, UT 84112 USA. Natl Inst Drug Abuse, Chem & Pharmaceut Branch, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. RP Compton, P (reprint author), Univ Calif Los Angeles, Sch Nursing, Factor Bldg 4-246,Box 956918, Los Angeles, CA 90095 USA. EM pcompton@sonnet.ucla.edu FU NIDA NIH HHS [N01DA-1-9205, N01DA-7-8074] NR 12 TC 27 Z9 28 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 15 PY 2006 VL 82 IS 1 BP 25 EP 31 DI 10.1016/j.drugalcdep.2005.08.005 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 025BA UT WOS:000236239100004 PM 16144748 ER PT J AU Shen, HM Liu, ZG AF Shen, HM Liu, ZG TI JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE JNK; oxidative stress; reactive oxygen species; nitrosative stress; reactive nitrogen species; apoptosis; necrosis; TNF-alpha; free radicals ID TUMOR-NECROSIS-FACTOR; N-TERMINAL KINASE; JUN NH2-TERMINAL KINASE; NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASE; STRESS-INDUCED APOPTOSIS; ALPHA-INDUCED APOPTOSIS; FACTOR-KAPPA-B; RECEPTOR-INTERACTING PROTEIN; METABOLIC OXIDATIVE STRESS AB c-Jun N-terminal kinase(JNK), or stress-activated protein kinase, is an important member of the mitogen-activated protein kinase superfamily, the members of which are readily activated by many environmental stimuli. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important groups of free radicals that are capable of eliciting direct damaging effects or acting as critical intermediate signaling molecules, leading to oxidative and nitrosative stress and a series of biological consequences. Recently there has been an increasing amount of research interest focusing on the regulatory role of JNK activation in ROS-and RNS-induced cellular responses. In this review we will first summarize and discuss some recent findings regarding the signaling mechanisms of ROS-or RNS-mediated JNK activation. Second, we will talk about the role of JNK in ROS-or RNS-mediated cell death (both apoptosis and necrosis). Finally, we will analyze the emerging evidence for the involvement of ROS and RNS as mediators in tumor necrosis factor alpha-induced apoptosis. Taken together, the accumulating knowledge about the ROS/RNS-induced JNK signaling pathway has greatly advanced our understanding of the complex processes deciding the Cellular responses to environmental stress. (C) 2005 Elsevier Inc. All rights reserved. C1 Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117597, Singapore. NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Shen, HM (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117597, Singapore. EM cofshm@nus.edu.sg RI SHEN, Han-Ming/B-5942-2011 OI SHEN, Han-Ming/0000-0001-7369-5227 NR 131 TC 332 Z9 347 U1 2 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2006 VL 40 IS 6 BP 928 EP 939 DI 10.1016/j.freeradbiomed.2005.10.056 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 027GX UT WOS:000236404100003 PM 16540388 ER PT J AU Bonini, MG Rota, C Tomasi, A Mason, RP AF Bonini, MG Rota, C Tomasi, A Mason, RP TI The oxidation of 2 ',7 '-dichlorofluorescin to reactive oxygen species: A self-fulfilling prophesy? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE peroxynitrite; peroxidase; DCF; DCFH; EPR; free radicals ID FREE-RADICAL FORMATION; FLUORESCENT DYE 2'-7'-DICHLOROFLUORESCEIN; HORSERADISH-PEROXIDASE; DIHYDRORHODAMINE 123; STRESS MEASUREMENTS; PEROXYNITROUS ACID; HYDROGEN-PEROXIDE; INTRACELLULAR OXIDATION; XANTHINE-OXIDASE; SKELETAL-MUSCLE AB The oxidation of 2',7'-dichlorofluorescin (DCFH) and its diacetate form (DCFHDA) by the HRP/peroxynitrite system was investigated. Both DCFH and DCFHDA were oxidized to fluorescent products. A major anomaly, however, was the observation that fluorescence continued to build Lip long after peroxynitrite total decomposition and the initial HRP compound I reduction, suggesting the production of oxidants by the system. Indeed, preformed HRP compound I was instantly reduced by DCFH and DCFHDA to compound II with the obligate formation of DCF center dot- semiquinone and DCFHDA-derived radicals. Catalase strongly inhibited fluorescence and EPR signals, suggesting the intermediate formation of H2O2. Taken together the data indicate that peroxynitrite rapidly oxidizes HRP to HRP compound I, which is reduced by DCFH and its diacetate form with the concomitant formation of DCF center dot- semiquinone and DCFH DA-derived radicals. These are oxidized by O-2, producing O-2(center dot-) - (as demonstrated by EPR and oxygen consumption experiments), which dismutates to produce H2O2, which serves to fuel further DCFH/DCFHDA oxidation via HRP catalysis. Also DCFHDA was shown to be considerably more resistant to oxidation than its hydrolyzed product DCFH, presumably because of the absence of the easily oxidizable phenol moieties. DCFHDA/DCFH have been used to study free radical production in a variety of systems. Our findings demonstrate that this assay is subject to a serious artifact in that it produces what it is purported to measure; therefore, its use in biological systems should be approached with caution. Published by Elsevier Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Modena & Reggio Emilia, Dept Biomed Sci, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Free Rad Metabolite Sect, I-41100 Modena, Italy. RP Bonini, MG (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. EM bonini@niehs.nih.gov OI Tomasi, Aldo/0000-0002-1356-3430 FU Intramural NIH HHS NR 40 TC 140 Z9 143 U1 4 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2006 VL 40 IS 6 BP 968 EP 975 DI 10.1016/j.freeradbiomed.2005.10.042 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 027GX UT WOS:000236404100007 PM 16540392 ER PT J AU Isenberg, JS Ridnour, LA Thomas, DD Wink, DA Roberts, DD Espey, MG AF Isenberg, JS Ridnour, LA Thomas, DD Wink, DA Roberts, DD Espey, MG TI Guanylyl cyclase-dependent chemotaxis of endothelial cells in response to nitric oxide gradients SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitric oxide; chemotaxis; gradient; Boyden chamber; free radical ID TUMOR ANGIOGENESIS; L-ARGININE; NO; MIGRATION; INHIBITION; MODULATION; MECHANISMS; PROLIFERATION; DICTYOSTELIUM; LOCALIZATION AB Nitric oxide (NO) is an important regulator of angiogenesis and neovascularization. The nature of endothelial cell motility responses to NO was examined using a Boyden chamber method. NO generated via decomposition of either DEA/NO or DETA/NO produced increases in human umbilical vein endothelial cell (HUVEC) chemotaxis, which were completely abrogated by ODQ, a soluble guanylyl cyclase inhibitor. Measurements of NO either directly by chemiluminescence or its chemistry with diamino fluorescein revealed that chemotaxis was driven by subtle NO gradients between the lower and the upper wells in this system. In addition to diffusion and volatilization from the upper chambers, the data showed that HUVEC consumption of NO contributed to these sustained gradients. Comparison of DEA/NO- and DETA/NO-mediated responses suggested that the persistence of spatial NO gradients is as significant as the absolute magnitude of NO exposure per unit time. The findings suggest that subnanomolar NO gradients are Sufficient to mobilize endothelial cell migration into hypoxic tissue during neovascularization events, such as in wound healing and cancer. Published by Elsevier Inc. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Isenberg, JS (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM isenberj@mail.nih.ogv; SP@nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 42 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2006 VL 40 IS 6 BP 1028 EP 1033 DI 10.1016/j.freeradbiomed.2005.10.053 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 027GX UT WOS:000236404100013 PM 16540398 ER PT J AU Donzelli, S Espey, MG Thomas, DD Mancardi, D Tocchetti, CG Ridnour, LA Paolocci, N King, SB Miranda, KM Lazzarino, G Fukuto, JM Wink, DA AF Donzelli, S Espey, MG Thomas, DD Mancardi, D Tocchetti, CG Ridnour, LA Paolocci, N King, SB Miranda, KM Lazzarino, G Fukuto, JM Wink, DA TI Discriminating formation of HNO from other reactive nitrogen oxide species SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE nitroxyl; nitric oxide; Angeli's salt; IPA/NO; glutathione; sulfinamide; thiol; S-nitrosothiol; hydroxylamine N-G-hydroxy-L-arginine; HPLC free; radicals ID HYDROXY-L-ARGININE; DETERRENT AGENT CYANAMIDE; NEUTRAL AQUEOUS-SOLUTION; FREE NITRIC-OXIDE; NO-CENTER-DOT; S-NITROSOTHIOLS; NITROSYL HYDRIDE; NITROXYL ANION; L-CYSTEINE; ALDEHYDE DEHYDROGENASE AB Nitroxyl (HNO) exhibits unique pharmacological properties that often oppose those of nitric oxide (NO), in part due to differences in reactivity toward thiols. Prior investigations suggested that the end products arising from the association of HNO with thiols were condition-dependent, but were inconclusive as to product identity. We therefore used HPLC techniques to examine the chemistry of HNO with glutathione (GSH) in detail. Under biological conditions, exposure to HNO donors converted GSH to both the sulfinamide [GS(O)NH2] and the oxidized thiol (GSSG). Higher thiol concentrations generally favored a higher GSSG ratio, Suggesting that the products resulted from competitive consumption of a single intermediate (GSNHOH). Formation of GS(O)NH2 was not observed with other nitrogen oxides (NO, N2O3 NO2, or ONOO-), indicating that it is a unique product of the reaction of HNO with thiols. The HPLC assay was able to detect submicromolar concentrations of GS(O)NH2. Detection of GS(O)NH2 was then used as a marker for HNO production from several proposed biological pathways, including thiol-mediated decomposition of S-nitrosothiols and peroxidase-driven oxidation of hydroxylamine (an end product of the reaction between GSH and HNO) and N-G-hydroxy-L-arginine (an NO synthase intermediate). These data indicate that free HNO can be biosynthesized and thus may function as an endogenous signaling agent that is regulated by GSH content. Published by Elsevier Inc. C1 NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA. Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. Univ Catania, Dept Chem Sci, Biochem Lab, I-95125 Catania, Italy. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. EM wink@mail.nih.gov RI Miranda, Katrina/B-7823-2009; OI tocchetti, carlo gabriele/0000-0001-5983-688X; MANCARDI, Daniele/0000-0003-3809-6047; lazzarino, giuseppe/0000-0002-5917-7279; Paolocci, Nazareno/0000-0001-7011-997X FU Intramural NIH HHS NR 87 TC 62 Z9 62 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2006 VL 40 IS 6 BP 1056 EP 1066 DI 10.1016/j.freeradbiomed.2005.10.058 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 027GX UT WOS:000236404100016 PM 16540401 ER PT J AU Zhang, ZJ Kim, SJ Chowdhury, B Wang, JY Lee, YC Tsai, PC Choi, M Mukherjee, AB AF Zhang, ZJ Kim, SJ Chowdhury, B Wang, JY Lee, YC Tsai, PC Choi, M Mukherjee, AB TI Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell motility and invasion SO GENE LA English DT Article DE Clara cell 10 kDa protein; Secretoglobin; extracellular matrix; green fluorescent protein ID BLASTOCYST DEVELOPMENT; EXPRESSION; BINDING; PROTEIN; GENE AB Cellular migration and invasion are critical for important biological processes including cancer metastasis. We previously reported that uteroglobin (UG), a multifunctional secreted protein, binds to several cell types inhibiting migration and invasion [G.C. Kundu, A.K. Z. Zhang Mandal, G. Mantile-Selvaggi, A.B. Mukherjee (1998) Uteroglobin (UG) suppresses extracellular matrix invasion by normal and cancer cells that express the high affinity UG-binding proteins. J Biol Chem. 273: 22819-22824]. More recently, we reported that HTB-81 adenocarcinoma cells, which do not bind UG, are refractory to UG-mediated inhibition of migration and invasion [Z. Zhang, G.C. Kundu, D. Panda, A.K. Mandal et al. (1999) Loss of transformed phenotype in cancer cells by overexpression of the uteroglobin gene. Proc Natl Acad Sci U S A. 96, 3963-3968]. Since UG shares several biological properties with lipocalin-1 that mediates some of its biological effects via its receptor (Lip-1R), we sought to determine whether UG might interact with Lip-1R and inhibit migration and invasion of HTB-81 cells. To address this question, we first transfected COS-1 cells, which do not bind UG, with a Lip-1R-cDNA construct and performed binding assays using I-125-human UG (hUG). The results show that hUG binds Lip-1R on these cells with high specificity. Further, transfection of HTB-81 cells with the same construct yielded I-125- hUG binding with high affinity (K-d = 18 nM) and specificity. The hUG-Lip-1R interaction was further confirmed by transfecting HTB-81, HTB-30 and HTB-174 cells, which are refractory to UG-binding, with a green fluorescent protein (GFP)-Lip-1R-cDNA construct and testing for Lip-1R-hUG colocalization by fluorescence microscopy. Finally, we demonstrate that Lip-1R-hUG interaction on Lip-1R transfected HTB-81 cells renders them fully responsive to hUG-mediated inhibition of migration and invasion. Taken together, these results suggest that Lip-1R is at least one of the UG-binding proteins through which UG exerts anti-motility and anti-invasive effects. Published by Elsevier B.V. C1 NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Intramural NIH HHS NR 16 TC 16 Z9 20 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 15 PY 2006 VL 369 BP 66 EP 71 DI 10.1016/j.gene.2005.10.027 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 028QL UT WOS:000236503000008 PM 16423471 ER PT J AU Correa-Cerro, LS Wassif, CA Kratz, L Miller, GF Munasinghe, JP Grinberg, A Fliesler, SJ Porter, FD AF Correa-Cerro, LS Wassif, CA Kratz, L Miller, GF Munasinghe, JP Grinberg, A Fliesler, SJ Porter, FD TI Development and characterization of a hypomorphic Smith-Lemli-Opitz syndrome mouse model and efficacy of simvastatin therapy SO HUMAN MOLECULAR GENETICS LA English DT Article ID 7-DEHYDROCHOLESTEROL REDUCTASE GENE; DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; BLOOD-BRAIN-BARRIER; 3-BETA-HYDROXYSTEROL DELTA(7)-REDUCTASE; MALFORMATION SYNDROMES; DIETARY-CHOLESTEROL; INBORN-ERRORS; DEFICIENCY; SUPPLEMENTATION; LIVER AB Smith-Lemli-Opitz syndrome (SLOS) is a genetic syndrome caused by mutations in the 3 beta-hydroxysterol Delta(7)-reductase gene (DHCR7). SLOS patients have decreased cholesterol and increased 7-dehydrocholesterol (7-DHC) levels. Dietary cholesterol supplementation improves systemic biochemical abnormalities; however, because of the blood-brain barrier, the central nervous system (CNS) is not treated. Simvastatin therapy has been proposed as a means to treat the CNS. Mice homozygous for a null disruption of Dhcr7, Dhcr7(Delta 3-5/Delta 3-5), die soon after birth, thus they cannot be used to study postnatal development or therapy. To circumvent this problem, we produced a hypomorphic SLOS mouse model by introducing a mutation corresponding to DHCR7(T93M). Both Dhcr7(T93M/T93M) and Dhcr7(Delta 3-5/T93M) mice are viable. Phenotypic findings in Dhcr7(T93M/Delta 3-5) mice include CNS ventricular dilatation and two to three syndactyly. Biochemically, both Dhcr7(T93M/T93M) and Dhcr7(T93M/Delta 3-5) mice have elevated tissue 7-DHC levels; however, the biochemical defect improved with age. This has not been observed in human patients, and is due to elevated Dhcr7 expression in mouse tissues. Dietary cholesterol therapy improved sterol profiles in peripheral, but not CNS tissues. However, treatment of Dhcr7(T93M/Delta 3-5) mice with simvastatin decreased 7-DHC levels in both peripheral and brain tissues. Expression of Dhcr7 increased in Dhcr7(T93M/Delta 3-5) tissues after simvastatin therapy, consistent with the hypothesis that simvastatin therapy improves the biochemical phenotype by increasing the expression of a Dhcr7 allele with residual enzymatic activity. We conclude that simvastatin treatment is efficacious in improving the SLOS-associated sterol abnormality found in the brain, and thus has the potential to be an effective therapeutic intervention for behavioral and learning problems associated with SLOS. C1 NICHHD, Unit Mol Dysmorphol, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, DHHS, Bethesda, MD USA. NIH, Mouse Imaging Facil, DHHS, Bethesda, MD USA. NIH, Lab Mammalian Genes & Dev, DHHS, Bethesda, MD USA. Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21218 USA. St Louis Univ, Inst Eye, St Louis, MO 63103 USA. St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63103 USA. RP Porter, FD (reprint author), NICHHD, Unit Mol Dysmorphol, Heritable Disorders Branch, NIH, Blvd 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov OI Wassif, Christopher/0000-0002-2524-1420 FU Intramural NIH HHS; NEI NIH HHS [EY07361] NR 50 TC 36 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 15 PY 2006 VL 15 IS 6 BP 839 EP 851 DI 10.1093/hmg/ddl003 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 018NS UT WOS:000235771800004 PM 16446309 ER PT J AU Rajkumar, T Appleby, P Beral, V Berrington, DA Bull, D Crossley, B Green, J Reeves, G Sweetland, S Kjaer, S Peto, J Painter, R Vessey, M Daling, J Madeleine, M Ray, R Thomas, D Hutchinson, F Hererro, R Ylitalo, N Bosch, FX Castellsague, X Hammouda, D Peto, J Negri, E Peto, J Santos, C Colin, D Franceschi, S Munoz, N Plummer, M Dillner, J Bayo, S Chaouki, N Rolon, P Brinton, L Hildesheim, A Lacey, J Schiffman, M Stein, L Hannaford, P Chichareon, S Sitas, F Eluf-Neto, J La Vecchia, C Skegg, D Pike, M Ursin, G Ngelangel, C Farley, T Meirik, O AF Rajkumar, T Appleby, P Beral, V Berrington, DA Bull, D Crossley, B Green, J Reeves, G Sweetland, S Kjaer, S Peto, J Painter, R Vessey, M Daling, J Madeleine, M Ray, R Thomas, D Hutchinson, F Hererro, R Ylitalo, N Bosch, FX Castellsague, X Hammouda, D Peto, J Negri, E Peto, J Santos, C Colin, D Franceschi, S Munoz, N Plummer, M Dillner, J Bayo, S Chaouki, N Rolon, P Brinton, L Hildesheim, A Lacey, J Schiffman, M Stein, L Hannaford, P Chichareon, S Sitas, F Eluf-Neto, J La Vecchia, C Skegg, D Pike, M Ursin, G Ngelangel, C Farley, T Meirik, O TI Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies - International collaboration of epidemiological studies of cervical cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE tobacco; cervical cancer; risk; meta-analysis ID ORAL-CONTRACEPTIVE USE; HUMAN-PAPILLOMAVIRUS INFECTION; RISK-FACTORS; INTRAEPITHELIAL NEOPLASIA; CIGARETTE-SMOKING; IN-SITU; SEXUAL-BEHAVIOR; UNITED-STATES; SOUTH-AFRICA; YOUNG-WOMEN AB Tobacco smoking has been classified as a cause of cervical cancer, but the effect of different patterns of smoking on risk is unclear. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 13,541 women with and 23,017 women without cervical carcinoma, from 23 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of carcinoma of the cervix in relation to tobacco smoking were calculated with stratification by study, age, sexual partners, age at first intercourse, oral contraceptive use and parity. Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p < 0.001). There was increased risk for past smokers also, though to a lesser extent (RR = 1.12 (1.01-1.25)), and there was no clear trend with time since stopping smoking (p-trend = 0.6). There was no association between smoking and adenocarcinoma of the cervix (RR = 0.89 (0.74-1.06) and 0.89 (0.72-1.10) for current and past smokers respectively), and the differences between the RRs for smoking and squamous cell and adenocarcinoma were statistically significant (current smoking p < 0.001 and past smoking p = 0.01). In current smokers, the RR of squamous cell carcinoma increased with increasing number of cigarettes smoked per day and also with younger age at starting smoking (p < 0.001 for each trend), but not with duration of smoking (p-trend = 0.3). Eight of the studies had tested women for cervical HPV-DNA, and in analyses restricted to women who tested positive, there was a significantly increased risk in current compared to never smokers for squamous cell carcinoma (RR = 1.95 (1.43-2.65)), but not for adenocarcinoma (RR = 1.06 (0.14-7.96)). In summary, smokers are at an increased risk of squamous cell but not of adenocarcinoma of the cervix. The risk of squamous cell carcinoma increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking. (c) 2005 Wile-y-Liss. Inc. C1 Canc Res UK, Epidemiol Unit, Epidemiol Grp, Wolfson Inst Prevent Med, Oxford OX3 7DG, England. Rajkumar T Canc Inst, WIA, Madras, Tamil Nadu, India. Canc Res UK, Epidemiol Unit, Oxford, England. LSHTM, Dept Epidemiol & Populat Hlth, London, England. Dept Publ Hlth, Oxford, England. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. Inst Nacl Sante Publ, Algiers, Algeria. Inst Canc Res, Sutton, Surrey, England. Ist Ric Farmacol Mario Negri, Milan, Italy. Inst Nacl Enfermedades Neoplascias Dr Eduardo Cac, Lima, Peru. Int Agcy Res Canc, F-69372 Lyon, France. Lund Univ, Malmo, Sweden. Minist Sante Publ & Affaires Sociales, Bamako, Mali. NCI, Bethesda, MD 20892 USA. Natl Hlth Lab Serv, Canc Epidemiol Res Grp, Johannesburg, South Africa. Prince Songkla Univ, Songkhla, Thailand. NSW Canc Council, Sydney, NSW, Australia. Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. Univ Milan, Milan, Italy. Univ Otago, Dunedin, New Zealand. Univ So Calif, Los Angeles, CA 90089 USA. Univ Philippines, Manila, Philippines. Univ Tromso, Tromso, Norway. WHO, CH-1211 Geneva, Switzerland. RP Berrington, DA (reprint author), Canc Res UK, Epidemiol Unit, Epidemiol Grp, Wolfson Inst Prevent Med, Richard Doll Bldg,Roosevelt Dr, Oxford OX3 7DG, England. EM aberring@jhsph.edu RI Beral, Valerie/B-2979-2013; Negri, Eva/B-7244-2013; Eluf-Neto, Jose/B-2522-2009; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012; Brinton, Louise/G-7486-2015; Castellsague Pique, Xavier/N-5795-2014 OI Negri, Eva/0000-0001-9712-8526; Eluf-Neto, Jose/0000-0001-7504-2115; BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Brinton, Louise/0000-0003-3853-8562; Castellsague Pique, Xavier/0000-0002-0802-3595 NR 48 TC 169 Z9 174 U1 0 U2 12 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 MAR 15 PY 2006 VL 118 IS 6 BP 1481 EP 1495 PG 15 WC Oncology SC Oncology GA 014JW UT WOS:000235477100021 ER PT J AU Valencia, JC Watabe, H Chi, A Rouzaud, F Chen, KG Vieira, WD Takahashi, K Yamaguchi, Y Berens, W Nagashima, K Shabanowitz, J Hunt, DF Appella, E Hearing, VJ AF Valencia, JC Watabe, H Chi, A Rouzaud, F Chen, KG Vieira, WD Takahashi, K Yamaguchi, Y Berens, W Nagashima, K Shabanowitz, J Hunt, DF Appella, E Hearing, VJ TI Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes SO JOURNAL OF CELL SCIENCE LA English DT Article DE Pmel17; plasma membrane; AP1; AP2; melanocytes ID CLATHRIN ADAPTER COMPLEXES; EPITHELIAL-CELLS; INTRACELLULAR TRAFFICKING; MASS-SPECTROMETRY; MESSENGER-RNA; PROTEINS; EXPRESSION; TYROSINASE; SIGNALS; SUBUNIT AB Adaptor proteins (AP) play important roles in the sorting of proteins from the trans-Golgi network, but how they function in the sorting of various melanosome-specific proteins such as Pmel17, an essential structural component of melanosomes, in melanocytes is unknown. We characterized the processing and trafficking of Pmel17 via adaptor protein complexes within melanocytic cells. Proteomics analysis detected Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time PCR, immunolabeling and tissue in-situ hybridization confirmed the coexpression of AP1 isoforms mu 1A and mu 1B (expressed only in polarized cells) in melanocytes and keratinocytes, but expression of mu 1B is missing in some melanoma cell lines. Transfection with AP1 isoforms (mu 1A or mu 1B) showed two distinct distribution patterns that involved Pmel17, and only mu 1B was able to restore the sorting of Pmel17 to the plasma membrane in cells lacking mu 1B expression. Finally, we established that expression of mu 1B is regulated physiologically in melanocytes by UV radiation or DKK1. These results show that Pmel17 is sorted to melanosomes by various intracellular routes, directly or indirectly through the plasma membrane, and the presence of basolateral elements in melanocytes suggests their polarized nature. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Image Anal Lab, Frederick, MD 21702 USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008; Chen, Kevin/D-6769-2011; Hunt, Donald/I-6936-2012 OI Chen, Kevin/0000-0003-2983-6330; Hunt, Donald/0000-0003-2815-6368 FU Intramural NIH HHS [Z99 NS999999]; NIGMS NIH HHS [GM 37537, R01 GM037537] NR 43 TC 36 Z9 40 U1 2 U2 3 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 MAR 15 PY 2006 VL 119 IS 6 BP 1080 EP 1091 DI 10.1242/jcs.02804 PG 12 WC Cell Biology SC Cell Biology GA 031AV UT WOS:000236677400015 PM 16492709 ER PT J AU Robertson, SJ Messer, RJ Carmody, AB Hasenkrug, KJ AF Robertson, Shelly J. Messer, Ronald J. Carmody, Aaron B. Hasenkrug, Kim J. TI In vitro suppression of CD8(+) T cell function by friend virus-induced regulatory T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; HIV-INFECTED PATIENTS; RETROVIRUS INFECTION; GAMMA-INTERFERON; IMMUNE-RESPONSES; DENDRITIC CELLS; HELPER TYPE-1; CUTTING EDGE AB Regulatory T cell (Treg)-mediated suppression of CD8(+) T cells has been implicated in the establishment and maintenance of chronic viral infections, but little is known about the mechanism of suppression. In this study an in vitro assay was I developed to investigate the suppression of CD8(+) T cells by Friend retrovirus (FV)-induced Tregs. CD4(+)CD25(+) T cells isolated from mice chronically infected with the FV suppressed the development of effector function in naive CD8(+) T cells without affecting their ability to proliferate or up-regulate activation markers. In vitro restimulation was not required for suppression by FV-induced Tregs, correlating with their high activation state in vivo. Suppression was mediated by direct T cell-T cell interactions and occurred in the absence of APCs. Furthermore, suppression occurred irrespective of the TCR specificity of the CD8(+) T cells. Most interestingly, FV-induced Tregs were able to suppress the function of CD8(+) effector T cells that had been physiologically activated during acute FV infection. The ability to suppress the effector function of activated CTLs is likely a requisite role for Tregs in limiting immunopathology by CD8(+) T cells during antiviral immune responses. Such activity may also have adverse consequences by allowing viruses to establish and maintain chronic infections if suppression of antiviral immune responses occurs before virus eradication. 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 FU Intramural NIH HHS NR 77 TC 56 Z9 63 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2006 VL 176 IS 6 BP 3342 EP 3349 PG 8 WC Immunology SC Immunology GA 059YP UT WOS:000238768400008 PM 16517701 ER PT J AU Liu, KB Caldwell, SA Greeneltch, KM Yang, DF Abrams, SI AF Liu, Kebin Caldwell, Sheila A. Greeneltch, Kristy M. Yang, Dafeng Abrams, Scott I. TI CTL adoptive immunotherapy concurrently mediates tumor regression and tumor escape SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLON-CARCINOMA CELLS; FLICE-INHIBITORY PROTEIN; FAS LIGAND INTERACTIONS; ANTIGEN-LOSS VARIANTS; IN-VIVO; METASTATIC MELANOMA; IFN-GAMMA; PULMONARY METASTASES; IMMUNE ESCAPE; T-CELLS AB Tumor escape and recurrence are major impediments for successful immunotherapy. It is well-documented that the emergence of Ag-loss variants, as well as regulatory mechanisms suppressing T cell function, have been linked to inadequate antitumor activity. However, little is known regarding the role of Fas-mediated cytotoxicity by tumor-specific CD8(+) CTL in causing immune evasion of Fas resistant variants during adoptive immunotherapy. In this study, we made use of an adoptive transfer model of experimental lung metastasis using tumor-specific CTL as a relevant immune-based selective pressure, and wherein the Fas ligand pathway was involved in the antitumor response. Surviving tumor cells were recovered and examined for alterations in antigenic, functional, and biologic properties. We showed that diminished susceptibility to Fas-mediated cytotoxicity in vivo was an important determinant of tumor escape following CTL-based immunotherapy. Tumor escape variants (TEV) recovered from the lungs of CTL-treated mice exhibited more. aggressive behavior in vivo. However, these TEV retained relevant MHC class I and tumor Ag expression and sensitivity to CTL via the perforin pathway but reduced susceptibility to Fas-mediated lysis. Moreover, TEV were significantly less responsive to eradication by CTL adoptive immunotherapy paradigms as a consequence of increased Fas resistance. Overall, we identified that Fas(low)-TEV emerged as a direct consequence of CTL-tumor interactions in vivo, and that such an altered neoplastic Fas phenotype compromised immunotherapy efficacy. Together, these findings may have important implications for both tumor progression and the design of immunotherapeutic interventions to confront these selective pressures or escape mechanisms. C1 NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. EM sa47z@nih.gov OI Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS NR 48 TC 25 Z9 28 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2006 VL 176 IS 6 BP 3374 EP 3382 PG 9 WC Immunology SC Immunology GA 059YP UT WOS:000238768400012 PM 16517705 ER PT J AU Okazaki, T Pendleton, CD Sarobe, P Thomas, EK Iyengar, S Harro, C Schwartz, D Berzofsky, JA AF Okazaki, Takahiro Pendleton, C. David Sarobe, Pablo Thomas, Elaine K. Iyengar, Sujatha Harro, Clayton Schwartz, David Berzofsky, Jay A. TI Epitope enhancement of a CD4 HIV epitope toward the development of the next generation HIV vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; CD8-T-CELL MEMORY; CD4-T-CELL HELP; ACUTE INFECTION; PEPTIDE; MICE; INDIVIDUALS; LYMPHOCYTES; ENVELOPE AB Virus-specific CD4(+) T cell help and CD8(+) cytotoxic T cell responses are critical for maintenance of effective immunity in chronic viral infections. The importance of CD4(+) T cells has been documented in HIV infection. To investigate whether a stronger CD4(+) T cell response can be induced by modifications to enhance the T1 epitope, the first CD4(+) T cell epitope discovered in HIV-1-gp120, we developed a T1-specific CD4(+) T cell line from a healthy volunteer immunized with a canarypox vector expressing gp120 and boosted with recombinant gp120. This T1-specific CD4(+) T cell line was restricted to DR13, which is common in U.S. Caucasians and African-Americans and very frequent in Africans. Peptides with certain amino acid substitutions in key positions induced enhanced specific CD4(+) T cell proliferative responses at lower peptide concentration than the original epitope. This relatively conserved CD4 epitope improved by the epitope enhancement strategy could be a component of a more effective second generation vaccine construct for HIV infection. C1 NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. Johns Hopkins Univ, Ctr Immunizat Res, Baltimore, MD 21205 USA. RP Berzofsky, JA (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bldg 10,Room 6B-12,MSC 1578, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov RI Sarobe, Pablo/D-6976-2017 OI Sarobe, Pablo/0000-0003-0503-7905 FU Intramural NIH HHS NR 34 TC 11 Z9 12 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2006 VL 176 IS 6 BP 3753 EP 3759 PG 7 WC Immunology SC Immunology GA 059YP UT WOS:000238768400051 PM 16517744 ER PT J AU Cui, XZ Li, Y Li, XM Haley, M Moayeri, M Fitz, Y Leppla, SH Eichacker, PQ AF Cui, XZ Li, Y Li, XM Haley, M Moayeri, M Fitz, Y Leppla, SH Eichacker, PQ TI Sublethal doses of Bacillus anthracis lethal toxin inhibit inflammation with lipopolysaccharide and Escherichia coli challenge but have opposite effects on survival SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 101st International Conference of the American-Thoracic-Society CY MAY 20-25, 2005 CL San Diego, CA SP Amer Thorac Soc, Fogarty AIDS Int Training & Res Program ID NITRIC-OXIDE SYNTHESIS; FACTOR CLEAVES; TNF-ALPHA; SEPSIS; MACROPHAGES; SHOCK; RATS; PERITONITIS; ACTIVATION; COMPONENTS AB Background. On the basis of the findings of previous in vitro studies, we hypothesized that anthrax lethal toxin (LeTx) would have anti-inflammatory effects in vivo. Methods. We investigated the effects of sublethal doses of LeTx in rats receiving intravascular challenge with lipopolysaccharide (LPS) or intratracheal challenge with Escherichia coli. Results. In rats receiving 24-h infusions of LPS, compared with control rats, pretreatment with high or low sublethal doses of LeTx 3 h before infusion produced similar patterns of reduction in the hazards ratio (HR) of survival at 168 h (0.60 [95% confidence interval {CI}, 0.37-0.98];, for the doses combined). LeTx increased mean arterial blood pressure throughout the period of LPS infusion (P = .001); decreased the levels of 10 of 13 cytokines assessed (i.e., interleukin [IL]-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-10, interferon-gamma, tumor necrosis factor-alpha, granulocyte macrophage-colony-stimulating factor, migratory inhibitory protein [MIP]-1 alpha, MIP-2, MIP-3 alpha, and RANTES) at 2 h; decreased all 13 cytokine levels at 8 h; decreased only 4 cytokine levels at 24 h; and decreased the plasma level of nitric oxide (NO) at 8 h and 24 h but not at 2 h (P <= .02, for the effect of LeTx, across time, on both cytokine levels and the NO level). Although pretreatment with LeTx before challenge with E. coli altered mean arterial blood pressure, cytokine levels, and the NO level in a pattern similar to that noted in association with LPS infusion, it increased the HR in a pattern different from that associated with LPS (4.36 [ 95% CI, 0.3-63.4];, for the effects of LeTx with LPS vs. E. coli). Conclusion. Inhibition of inflammation with LeTx can occur in vivo, and, although beneficial with noninfectious stimuli, it may be harmful with bacteria. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov FU Intramural NIH HHS NR 32 TC 23 Z9 24 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 MAR 15 PY 2006 VL 193 IS 6 BP 829 EP 840 DI 10.1086/500468 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 015FB UT WOS:000235536200014 PM 16479518 ER PT J AU Cabral, ES Gelderblom, H Hornung, RL Munson, PJ Martin, R Marques, AR AF Cabral, ES Gelderblom, H Hornung, RL Munson, PJ Martin, R Marques, AR TI Borrelia burgdorferi lipoprotein-mediated TLR2 stimulation causes the down-regulation of TLR5 in human monocytes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOLL-LIKE RECEPTOR-2; NF-KAPPA-B; ENDOTOXIN-TOLERANT CELLS; INNATE IMMUNE-RESPONSE; GENE-EXPRESSION; CUTTING EDGE; IRAK-M; TREPONEMA-PALLIDUM; NEGATIVE REGULATOR; DENDRITIC CELLS AB Toll-like receptors (TLRs) trigger innate immune responses via the recognition of conserved pathogen-associated molecular patterns. Lipoproteins from Borrelia burgdorferi, the agent of Lyme disease, activate inflammatory cells through TLR2 and TLR1. We show that stimulation of human monocytes with B. burgdorferi lysate, lipidated outer surface protein A, and triacylated lipopeptide Pam(3)CysSerLys(4) results in the up-regulation of both TLR2 and TLR1 but the down-regulation of TLR5,the receptor for bacterial flagellin, and that this effect is mediated via TLR2. TLR4 stimulation had no effect on TLR2, TLR1, and TLR5 expression. Human monocytes stimulated with TLR5 ligands (including p37 or flaA, the minor protein from B. burgdorferi flagella) up-regulated TLR5. In addition, TLR2 stimulation rendered cells hyporesponsive to a TLR5 agonist. These results indicate that diverse stimuli can cause differential TLR expression, and we hypothesize that these changes may be useful for either the pathogen and/or the host. C1 NIAID, Clin Studies Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NINDS, Cellular Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. SAIC Frederick Inc, Clin Serv Program, NCI Frederick, Frederick, MD USA. RP Marques, AR (reprint author), NIAID, Clin Studies Unit, Lab Clin Infect Dis, NIH, Bldg 10 Rm 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM amarques@niaid.nih.gov FU Intramural NIH HHS NR 52 TC 31 Z9 31 U1 1 U2 4 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 MAR 15 PY 2006 VL 193 IS 6 BP 849 EP 859 DI 10.1086/500467 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 015FB UT WOS:000235536200016 PM 16479520 ER PT J AU Simonsen, L Taylor, RJ Elixhauser, A Viboud, C Kapikian, AZ AF Simonsen, L Taylor, RJ Elixhauser, A Viboud, C Kapikian, AZ TI Age dependence of the relation between reassortant rotavirus vaccine (RotaShield) and intussusception - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 NIAID, Off Global Affairs, NIH, Bethesda, MD 20892 USA. NIAID, Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. Agcy Hlth Care Res & Qual, Bethesda, MD USA. RP Simonsen, L (reprint author), NIAID, Off Global Affairs, NIH, 6610 Rockledge Dr,Rm 2033 MSC 7630, Bethesda, MD 20892 USA. EM lsimonsen@niaid.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 7 TC 4 Z9 4 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 MAR 15 PY 2006 VL 193 IS 6 BP 898 EP 899 DI 10.1086/500221 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 015FB UT WOS:000235536200022 ER PT J AU Yao, YF Vuong, C Kocianova, S Villaruz, AE Lai, YP Sturdevant, DE Otto, M AF Yao, YF Vuong, C Kocianova, S Villaruz, AE Lai, YP Sturdevant, DE Otto, M TI Characterization of the Staphylococcus epidermidis accessory-gene regulator response: Quorum-sensing regulation of resistance to human innate host defense SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PHENOL-SOLUBLE MODULINS; ANTIMICROBIAL PEPTIDES; IMMUNE EVASION; SAR LOCUS; AUREUS; VIRULENCE; INFECTIONS; AGR; IDENTIFICATION; INACTIVATION AB Staphylococci are important opportunistic pathogens. However, there is a lack of information on how these bacteria survive inside the human body during infection. This study demonstrates that quorum-sensing regulation in Staphylococcus epidermidis protects it from key mechanisms of human innate host defense. To gain a better understanding of the basis of the observed phenotype, the agr quorum-sensing regulon of S. epidermidis was characterized by a genomewide analysis of gene expression. The gene-expression data indicate that agr adapts bacterial physiology to stationary growth and, furthermore, that it controls a series of virulence factors, including degradative exoenzymes possibly involved in resistance to antimicrobial peptides. Remarkably, agr also regulates general and oxidative stress-response factors, including detoxifying enzymes of reactive oxygen species. Taken together, the results of this study indicate that quorum-sensing regulation in staphylococci has important, previously unknown functions that contribute to protection from mechanisms of human innate host defense-and, therefore, to the pathogen's survival in the human host. C1 NIH, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIAID, Hamilton, MT 59840 USA. E China Normal Univ, Mol Biol Lab, Sch Life Sci, Shanghai, Peoples R China. RP Otto, M (reprint author), NIH, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIAID, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov NR 33 TC 4 Z9 4 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2006 VL 193 IS 6 BP 941 EP 948 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 015FB UT WOS:000235536200015 ER PT J AU Mayer, ML Ghosal, A Dolman, NP Jane, DE AF Mayer, ML Ghosal, A Dolman, NP Jane, DE TI Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate receptor; kainate; structure; gating; antagonist; crystallography ID PARTIAL AGONIST ACTION; GLUTAMATE-RECEPTOR; ION CHANNELS; NMDA RECEPTORS; AMPA RECEPTORS; SUBUNIT; MECHANISM; ACTIVATION; DYNAMICS; MODEL AB Glutamate receptor (GluR) ion channels mediate fast synaptic transmission in the mammalian CNS. Numerous crystallographic studies, the majority on the GluR2-subtype AMPA receptor, have revealed the structural basis for binding of subtype-specific agonists. In contrast, because there are far fewer antagonist-bound structures, the mechanisms for antagonist binding are much less well understood, particularly for kainate receptors that exist as multiple subtypes with a distinct biology encoded by the GluR5-7, KA1, and KA2 genes. We describe here high-resolution crystal structures for the GluR5 ligand-binding core complex with UBP302 and UBP310, novel GluR5-selective antagonists. The crystal structures reveal the structural basis for the high selectivity for GluR5 observed in radiolabel displacement assays for the isolated ligand binding cores of the GluR2, GluR5, and GluR6 subunits and during inhibition of glutamate-activated currents in studies on full-length ion channels. The antagonists bind via a novel mechanism and do not form direct contacts with the E723 side chain as occurs in all previously solved AMPA and kainate receptor agonist and antagonist complexes. This results from a hyperextension of the ligand binding core compared with previously solved structures. As a result, in dimer assemblies, there is a 22 angstrom extension of the ion channel linkers in the transition from antagonist- to glutamate-bound forms. This large conformational change is substantially different from that described for AMPA receptors, was not possible to predict from previous work, and suggests that glutamate receptors are capable of much larger movements than previously thought. C1 NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Univ Bristol, MRC, Ctr Synapt Plastic, Dept Pharmacol, Bristol BS8 1TD, Avon, England. RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, Dept Hlth & Human Serv,NIH, Bldg 35,Room 3B 1002,35 Lincoln Dr, Bethesda, MD 20892 USA. EM mayerm@mail.nih.gov RI Mayer, Mark/H-5500-2013 FU Biotechnology and Biological Sciences Research Council [BB/C507045/1]; Intramural NIH HHS NR 48 TC 81 Z9 86 U1 0 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 MAR 15 PY 2006 VL 26 IS 11 BP 2852 EP 2861 DI 10.1523/JNEUROSCI.0123-06.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 021QU UT WOS:000236000400002 PM 16540562 ER PT J AU Chen, ZG Shen, J AF Chen, ZG Shen, J TI Single-shot echo-planar functional magnetic resonance imaging of representations of the fore- and hindpaws in the somatosensory cortex of rats using an 11.7 T microimager SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE fMRI; EPT; BOLD; forepaw representation; hindpaw representation; vertical microimager; rat brain; aminophylline ID BOLD FMRI; ANESTHETIZED RATS; ALPHA-CHLORALOSE; GRADIENT-ECHO; STIMULATION; BRAIN; MRI; OXYGENATION; PULSES; TESLA AB Most of functional magnetic resonance imaging (fMRI) experiments have been performed on horizontal bore magnets. Here, we present practical aspects of fMRI based on single-shot, spin-echo echo-planar imaging (EPI) using a widely available, cost effective 89 mm bore vertical 11.7 T microimager. It was demonstrated that reproducible, high-quality fMRI data can be obtained from alpha-chloralose anesthetized adult rat brain. Both coronal and the more extended horizontal EPI images were acquired to measure blood oxygenation level dependent (BOLD) responses to electrical stimulation of fore- and hindpaws. The BOLD patterns observed match the known representations of fore- and hindpaws in the somatosensory cortex in rats. Preliminary results on BOLD signal enhancement using aminophylline are also presented. (c) 2005 Elsevier B.V. All rights reserved. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Radiol, Beijing 100730, Peoples R China. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,900 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 38 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAR 15 PY 2006 VL 151 IS 2 BP 268 EP 275 DI 10.1016/j.jneumeth.2005.08.003 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 025IA UT WOS:000236257600022 PM 16168491 ER PT J AU Ma, WY Korngreen, A Weil, S Cohen, EBT Priel, A Kuzin, L Silberberg, SD AF Ma, WY Korngreen, A Weil, S Cohen, EBT Priel, A Kuzin, L Silberberg, SD TI Pore properties and pharmacological features of the P2X receptor channel in airway ciliated cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ION-CHANNEL; INTRACELLULAR CALCIUM; FUNCTIONAL EVIDENCE; EPITHELIAL-CELLS; SELECTIVITY; SUBUNITS; PERMEATION; BRAIN; PERMEABILITY; COEXPRESSION AB Airway ciliated cells express an ATP-gated P2X receptor channel of unknown subunit composition (P2X(cilia)) which is modulated by Na+ and by long exposures to ATP. P2X(cilia) was investigated by recording currents from freshly dissociated rabbit airway ciliated cells with the patch-clamp technique in the whole-cell configuration. During the initial continuous exposure to extracellular ATP, P2X(cilia) currents gradually increase in magnitude (priming), yet the permeability to N-methyl-D-glucamine (NMDG) does not change, indicating that priming does not arise from a progressive change in pore diameter. Na+, which readily permeates P2X(cilia) receptor channels, was found to inhibit the channel extracellular to the electric field. The rank order of permeability to various monovalent cations is: Li+, Na+, K+, Rb+, Cs+, NMDG(+) and TEA(+), with a relative permeability of 1.35, 1.0, 0.99, 0.91, 0.79, 0.19 and 0.10, respectively. The rank order for the alkali cations follows an Eisenman series XI for a high-strength field site. Ca2+ has been estimated to be 7-fold more permeant than Na+. The rise in [Ca2+](i) in ciliated cells, induced by the activation of P2X(cilia), is largely inhibited by either Brilliant Blue G or KN-62, indicating that P2X(7) may be a part of P2X(cilia). P2X(cilia) is augmented by Zn2+ and by ivermectin, and P2X(4) receptor protein is detected by immunolabelling at the basal half of the cilia, strongly suggesting that P2X(4) is a component of P2X(cilia) receptor channels. Taken together, these results suggest that P2X(cilia) is either assembled from P2X(4) and P2X(7) subunits, or formed from modified P2X(4) subunits. C1 Ben Gurion Univ Negev, Dept Chem, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel. Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. Bar Ilan Univ, Leslie & Susan Gonda Interdisciplinary Brain Res, IL-52900 Ramat Gan, Israel. RP Silberberg, SD (reprint author), Inst Neurol Disorders & Stroke, Porter Neurosci Res Ctr 3B211, NIH, 35 Convent Dr,MSC 3701, Bethesda, MD 20892 USA. EM silberbs@ninds.nih.gov OI Korngreen, Alon/0000-0002-2036-6160 NR 60 TC 54 Z9 54 U1 0 U2 1 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 MAR 15 PY 2006 VL 571 IS 3 BP 503 EP 517 DI 10.1113/jphysiol.2005.103408 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 020FO UT WOS:000235894000003 PM 16423852 ER PT J AU Lawrence, JJ Grinspan, ZM Statland, JM McBain, CJ AF Lawrence, JJ Grinspan, ZM Statland, JM McBain, CJ TI Muscarinic receptor activation tunes mouse stratum oriens interneurones to amplify spike reliability SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID OSCILLATIONS IN-VITRO; HIPPOCAMPAL INTERNEURONS; TIMING RELIABILITY; CORTICAL-NEURONS; VIVO; DIVERSITY; INPUT; CELLS AB Cholinergic activation of hippocampal targets can initiate and sustain network oscillations in vivo and in vitro, yet the impact of cholinergic modulation on the oscillatory properties of interneurones remains virtually unexplored. Using whole cell current clamp recordings in acute hippocampal slices, we investigated the influence of muscarinic receptor (mAChR) activation on the oscillatory properties of CA1 stratum oriens (SO) interneurones in vitro. In response to suprathreshold oscillatory input, mAChR activation increased spike reliability and precision, and extended the bandwidth that interneurone firing phase-locked. These suprathreshold effects were largest at theta frequencies, indicating that mAChR activation tunes active conductances to enhance firing reliability and precision to theta frequency input. Muscarinic tuning of the intrinsic oscillatory properties of interneurones is a novel mechanism that may be crucial for the genesis of the theta rhythm. C1 NICHD, LCSN, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Lawrence, JJ (reprint author), NICHD, LCSN, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 35,Rm 3C907, Bethesda, MD 20892 USA. EM lawrenjo@mail.nih.gov OI Grinspan, Zachary/0000-0001-6705-0932 FU Intramural NIH HHS NR 27 TC 36 Z9 37 U1 0 U2 1 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 MAR 15 PY 2006 VL 571 IS 3 BP 555 EP 562 DI 10.1113/jphysiol.2005.103218 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 020FO UT WOS:000235894000006 PM 16439425 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI The 2006 Retrovirology Prize: call for nominations SO RETROVIROLOGY LA English DT Editorial Material AB Retrovirology announces a nomination call for its 2006 prize to recognize an outstanding mid-career retrovirologist. The 2005 Retrovirology prize was awarded to Dr. Stephen P. Goff. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 2 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAR 15 PY 2006 VL 3 AR 17 DI 10.1186/1742-4690-3-17 PG 2 WC Virology SC Virology GA 067OK UT WOS:000239312300001 ER PT J AU Schiffer, WK Volkow, ND Fowler, JS Alexoff, DL Logan, J Dewey, SL AF Schiffer, WK Volkow, ND Fowler, JS Alexoff, DL Logan, J Dewey, SL TI Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine SO SYNAPSE LA English DT Article DE imaging; receptor; D-2; PET (positron emission tomography); striatum; microdialysis ID POSITRON-EMISSION-TOMOGRAPHY; VESICULAR MONOAMINE TRANSPORTER-2; FREELY MOVING RATS; IN-VIVO BINDING; HUMAN-BRAIN; NUCLEUS-ACCUMBENS; C-11 RACLOPRIDE; MESOLIMBIC DOPAMINE; DIALYSATE DOPAMINE; GRAPHICAL ANALYSIS AB Methylphenidate (MP) and amphetamine (AMP) are first-line treatments for attention-deficit hyperactivity disorder. Although both drugs have similar therapeutic potencies, the stimulatory effect of AMP on extracellular dopamine (ECF DA) is greater than that of MP. We compared extracellular effects directly against synaptic changes. ECF DA was assessed by microdialysis in freely moving rodents and synaptic dopamine (DA) was measured using PET and [C-11]-raclopride displacement in rodents and baboons. Microdialysis data demonstrated that MP (5.0 mg/kg, i.p.) increased ECF DA 360% +/- 31% in striatum, which was significantly less than that by AMP (2.5 mg/kg, i.p.; 1398% +/- 272%). This fourfold difference was not reflected by changes in synaptic DA. In fact, rodent PET studies showed no difference in striatal [C-11]-raclopride binding induced by AMP (2.5 mg/kg, i.p.; 25% +/- 4% reduction) compared with that by MP (5.0 mg/kg, i.p.; 21% +/- 4% reduction). Primate PET experiments also showed no differences between AMP (0.5 mg/kg, i.v.; 24% +/- 4% reduction) and MP (1.0 mg/kg, i.v.; 25% +/- 7% reduction) induced changes in [C-11]-raclopride binding potential. The similar potencies of MP and AMP to alter synaptic DA, despite their different potencies in raising ECF DA, could reflect their different molecular mechanisms. C1 Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. NIDA, Bethesda, MD 20892 USA. RP Schiffer, WK (reprint author), Brookhaven Natl Lab, Dept Chem, Bldg 555, Upton, NY 11973 USA. EM wynne@bnl.gov FU NIDA NIH HHS [DA06278, F31-DA01587, T32-DA07316] NR 67 TC 60 Z9 60 U1 1 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR 15 PY 2006 VL 59 IS 4 BP 243 EP 251 DI 10.1002/syn.20235 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 008MW UT WOS:000235045900006 PM 16385551 ER PT J AU Sinha, RK Alexander, C Mage, RG AF Sinha, RK Alexander, C Mage, RG TI Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE PNAd; L-selectin; B lymphocyte recruitment; appendix ID L-SELECTIN; ANTIBODY REPERTOIRE; VASCULAR ADDRESSIN; LYMPHOID-TISSUES; HOMING RECEPTOR; AVIAN BURSA; DIVERSIFICATION; CELLS; EQUIVALENT; FABRICIUS AB Young rabbit appendix is a homologue of chicken bursa of Fabricius; both are crucial sites for preimmune B-cell repertoire diversification. Here, we report that appendix regulates precursor lymphocyte recruitment for further development by modulating the sites of extravasation. The total area of peripheral node addressin-positive (PNAd(+)) high endothelial venules (HEVs) increased from I day to I week after birth, remained constant up to 2 weeks and declined to a low and persistent amount by 3 weeks. In normal I-week and manipulated 5-week appendix where growth of follicles was retarded, PNAd(+) HEVs were present in the basolateral sides of B-cell follicles whereas, in normal 5-wk-appendix these were restricted to T-cell areas. The PNAd was expressed on the lumenal surface of HEVs. The proportions of CD62L(+) B cells in appendix declined from similar to 40% at 3 days to 2-3% at 4 weeks. In lymphocyte transfer experiments, CD62L(+) B cells were preferentially recruited compared with CD62L(-) B cells, anti-PNAd antibody blocked migration of B cells by similar to 50%, and 100 times more B cells were recruited in I week compared to 6-week appendix. Thus, a unique spatiotemporal expression pattern of PNAd(+) HEVs is associated with development of B-cell follicles. This regulates migration of blood-borne B-lymphocytes into developing appendix by interacting with CD62L. (c) 2005 Elsevier B.V. All rights reserved. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM rsinha@niaid.nih.gov; rm3z@nih.gov NR 29 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD MAR 15 PY 2006 VL 110 IS 1-2 BP 97 EP 108 DI 10.1016/j.vetimm.2005.09.009 PG 12 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 018MO UT WOS:000235768700010 PM 16249036 ER PT J AU Zhang, PS Zhang, JH Sheng, HT Russo, JJ Osborne, B Buetow, K AF Zhang, PS Zhang, JH Sheng, HT Russo, JJ Osborne, B Buetow, K TI Gene functional similarity search tool (GFSST) SO BMC BIOINFORMATICS LA English DT Article ID BREAST-CANCER; SEMANTIC SIMILARITY; ONTOLOGY; ANNOTATION; DATABASE; BRCA1; GO AB Background: With the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood. Increasing amounts of data about genes, gene products and their functions have been stored in databases. To facilitate selection of candidate genes for gene-disease research, genetic association studies, biomarker and drug target selection, and animal models of human diseases, it is essential to have search engines that can retrieve genes by their functions from proteome databases. In recent years, the development of Gene Ontology ( GO) has established structured, controlled vocabularies describing gene functions, which makes it possible to develop novel tools to search genes by functional similarity. Results: By using a statistical model to measure the functional similarity of genes based on the Gene Ontology directed acyclic graph, we developed a novel Gene Functional Similarity Search Tool (GFSST) to identify genes with related functions from annotated proteome databases. This search engine lets users design their search targets by gene functions. Conclusion: An implementation of GFSST which works on the UniProt ( Universal Protein Resource) for the human and mouse proteomes is available at GFSST Web Server. GFSST provides functions not only for similar gene retrieval but also for gene search by one or more GO terms. This represents a powerful new approach for selecting similar genes and gene products from proteome databases according to their functions. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Columbia Univ, Columbia Genome Ctr, New York, NY USA. Cognia Corp, New York, NY USA. RP Zhang, PS (reprint author), NCI, Lab Populat Genet, Bethesda, MD 20892 USA. EM zhangpeis@mail.nih.gov; jinghuiz@mail.nih.gov; hs734@columbia.edu; jjr4@columbia.edu; brian_osborne@cognia.com; buetowk@nih.gov FU Intramural NIH HHS NR 18 TC 31 Z9 33 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 14 PY 2006 VL 7 AR 135 DI 10.1186/1471-2105-7-135 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 027LC UT WOS:000236416100001 PM 16536867 ER PT J AU Arnlov, J Evans, JC Wang, TJ Fox, CS Benjamin, EJ Levy, D D'Agostino, RB Vasan, RS Meigs, JB AF Arnlov, J Evans, JC Wang, TJ Fox, CS Benjamin, EJ Levy, D D'Agostino, RB Vasan, RS Meigs, JB TI Letter regarding article by Arnlov et al, "Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals" - Response SO CIRCULATION LA English DT Letter ID RISK-FACTORS; MICROALBUMINURIA; POPULATION; ADULTS; HEALTH C1 NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA. RP Arnlov, J (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. EM vasan@bu.edu RI Arnlov, Johan/N-9886-2013 NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 14 PY 2006 VL 113 IS 10 BP E406 EP E407 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 021GL UT WOS:000235971600022 ER PT J AU Piquemal, JP Cisneros, GA Reinhardt, P Gresh, N Darden, TA AF Piquemal, JP Cisneros, GA Reinhardt, P Gresh, N Darden, TA TI Towards a force field based on density fitting SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID INTERMOLECULAR INTERACTION ENERGY; POLARIZABLE MOLECULAR-MECHANICS; CHARGE-TRANSFER CONTRIBUTION; BASIS-SETS; ADDITIVE PROCEDURE; ELECTRON-DENSITY; WATER DIMER; POTENTIALS; COMPUTATIONS; ATOMS AB Total intermolecular interaction energies are determined with a first version of the Gaussian electrostatic model (GEM-0), a force field based on a density fitting approach using s-type Gaussian functions. The total interaction energy is computed in the spirit of the sum of interacting fragment ab initio (SIBFA) force field by separately evaluating each one of its components: electrostatic (Coulomb), exchange repulsion, polarization, and charge transfer intermolecular interaction energies, in order to reproduce reference constrained space orbital variation (CSOV) energy decomposition calculations at the B3LYP/aug-cc-pVTZ level. The use of an auxiliary basis set restricted to spherical Gaussian functions facilitates the rotation of the fitted densities of rigid fragments and enables a fast and accurate density fitting evaluation of Coulomb and exchange-repulsion energy, the latter using the overlap model introduced by Wheatley and Price [Mol. Phys. 69, 50718 (1990)]. The SIBFA energy scheme for polarization and charge transfer has been implemented using the electric fields and electrostatic potentials generated by the fitted densities. GEM-0 has been tested on ten stationary points of the water dimer potential energy surface and on three water clusters (n=16,20,64). The results show very good agreement with density functional theory calculations, reproducing the individual CSOV energy contributions for a given interaction as well as the B3LYP total interaction energies with errors below k(B)T at room temperature. Preliminary results for Coulomb and exchange-repulsion energies of metal cation complexes and coupled cluster singles doubles electron densities are discussed. (c) 2006 American Institute of Physics. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Paris 06, Chim Theor Lab, F-75252 Paris 05, France. INSERM, IFR Biomed, U648, Lab Pharmacochim Mol & Cellulaire, F-75006 Paris, France. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Piquemal, JP (reprint author), NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. EM piquemalj@niehs.nih.gov; darden@niehs.nih.gov RI Piquemal, Jean-Philip/B-9901-2009; Cisneros, Gerardo/B-3128-2010 OI Piquemal, Jean-Philip/0000-0001-6615-9426; FU Intramural NIH HHS [NIH0010197562, NIH0011757912]; PHS HHS [NIH0010197562, NIH0011757912] NR 68 TC 113 Z9 114 U1 0 U2 13 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 14 PY 2006 VL 124 IS 10 AR 104101 DI 10.1063/1.2173256 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 021MX UT WOS:000235988400003 PM 16542062 ER PT J AU Tilley, BC Palesch, YY Kieburtz, K Ravina, B Huang, P Elm, JJ Shannon, K Wooten, GF Tanner, CM Goetz, GC AF Tilley, BC Palesch, YY Kieburtz, K Ravina, B Huang, P Elm, JJ Shannon, K Wooten, GF Tanner, CM Goetz, GC CA NET-PD Investigators TI Optimizing the ongoing search for new treatments for Parkinson disease - Using futility designs SO NEUROLOGY LA English DT Review ID II CLINICAL-TRIALS; MULTIPLE TESTING PROCEDURE; 2-STAGE DESIGNS; LEVODOPA; DATATOP; SUPPLEMENTATION; RASAGILINE; STROKE AB Many agents are being considered for treatment of Parkinson disease (PD). Given the large number of agents and the limited resources to evaluate new agents, it is essential to reduce the likelihood of advancing ineffective agents into large, long-term Phase III trials. Futility design methodology addresses this goal. The authors describe how a single-arm Phase II futility study uses a short-term outcome to compare a treatment group response to a predetermined hypothesized or historically based control response. The authors present advantages and limitations of futility designs along with examples derived from the data archive of a large Phase III efficacy study of treatments to delay PD progression, the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. Using the same control progression rate and treatment effect assumptions used to power the original DATATOP trial, the authors calculated the number of subjects needed to conduct two 12-month futility studies. DATATOP was designed to enroll 800 patients. Using data on 124 consecutive subjects randomized into each of the DATATOP treatment groups, the authors identified tocopherol as futile and deprenyl as worthy of further study. Using Phase II information, DATATOP could have been simplified from a 2 x 2 factorial design to a comparison of deprenyl vs placebo. While not testing efficacy, futility designs provide a strategy for discarding treatments unlikely to be effective in Phase III. A limitation is the dependence on historical data or hypothesized outcomes for untreated controls. Futility studies may decrease the time to identify treatments unworthy of further pursuit and reduce subjects' exposure to futile treatments. C1 Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Univ Rochester, Dept Neurol, Rochester, NY USA. NINDS, NIH, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol, Charlottesville, VA USA. Parkinsons Inst, Sunnyvale, CA USA. RP Tilley, BC (reprint author), Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, POB 250835,135 Cannon St,Suite 303, Charleston, SC 29425 USA. EM tilleybc@musc.edu FU NINDS NIH HHS [U01NS043127, U01NS43128] NR 35 TC 50 Z9 51 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2006 VL 66 IS 5 BP 628 EP 633 DI 10.1212/01.wnl.0000201251.33253.fb PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 021GM UT WOS:000235971700005 PM 16534099 ER PT J AU Li, J Zhuang, Z Okamoto, H Vortmeyer, AO Park, DM Furuta, M Lee, YS Oldfield, EH Zeng, W Weil, RJ AF Li, J Zhuang, Z Okamoto, H Vortmeyer, AO Park, DM Furuta, M Lee, YS Oldfield, EH Zeng, W Weil, RJ TI Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers SO NEUROLOGY LA English DT Article ID GLIOBLASTOMA-MULTIFORME AB Methods to permit more precise delineation of astrocytomas of different grades may have therapeutic utility. The authors selectively microdissected pure populations of cells from normal brain and astrocytomas. They performed two-dimensional protein gel electrophoresis (2DGE) followed by protein sequencing. Differential expression was confirmed immunohistochemically. 2DGE identified proteomic patterns and proteins that differentiated normal brain from tumor and distinguished astrocytomas of increasing grade. C1 Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Saga Med Sch, Dept Neurosurg, Saga, Japan. Catholic Univ, Dept Pathol, Seoul, South Korea. Sun Yat Sen Univ, Zhongshan Med Coll, Dept Pathol, Guangzhou, Peoples R China. RP Weil, RJ (reprint author), Cleveland Clin Fdn, Brain Tumor Inst, ND4-40 Lerner Res Inst,9500 Euclid Ave, Cleveland, OH 44195 USA. EM weilr@ccf.org RI Park, Deric/C-5675-2013 FU NCRR NIH HHS [M01 RR-018390] NR 10 TC 16 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 14 PY 2006 VL 66 IS 5 BP 733 EP 736 DI 10.1212/01.wnl.0000201270.90502.d0 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 021GM UT WOS:000235971700023 PM 16534112 ER PT J AU Wu, L Bachrati, CZ Ou, JW Xu, C Yin, JH Chang, M Wang, WD Li, L Brown, GW Hickson, ID AF Wu, L Bachrati, CZ Ou, JW Xu, C Yin, JH Chang, M Wang, WD Li, L Brown, GW Hickson, ID TI BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Bloom's syndrome; Holliday junction dissolution; topoisomerase III; sister chromatid exchanges ID SYNDROME GENE-PRODUCT; SISTER-CHROMATID EXCHANGES; WERNERS-SYNDROME GENES; TOPOISOMERASE-III; RECQ HELICASES; BLOOM-SYNDROME; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; HOLLIDAY JUNCTIONS; REPLICATION FORKS AB BLM encodes a member of the highly conserved RecQ DNA helicase family, which is essential for the maintenance of genome stability. Homozygous inactivation of BLM gives rise to the cancer predisposition disorder Bloom's syndrome. A common feature of many RecQ helicase mutants is a hyperrecombination phenotype. In Bloom's syndrome, this phenotype manifests as an elevated frequency of sister chromatid exchanges and interhomologue recombination. We have shown previously that BLM, together with its evolutionarily conserved binding partner topoisomerase Ilia (hTOPO III alpha), can process recombination intermediates that contain double Holliday junctions into noncrossover products by a mechanism termed dissolution. Here we show that a recently identified third component of the human BLM/hTOPO III alpha complex, BLAP75/RMI1, promotes dissolution catalyzed by hTOPO III alpha. This activity of BLAP75/RMI1 is specific for dissolution catalyzed by hTOPO III alpha because it has no effect in reactions containing either Escherichia coli Top1 or Top3, both of which can also catalyze dissolution in a BLM-dependent manner. We present evidence that BLAP75/RMI1 acts by recruiting hTOPO III alpha to double Holliday junctions. Implications of the conserved ability of type IA topoisomerases to catalyze dissolution and how the evolution of factors such as BLAP75/RMI1 might confer specificity on the execution of this process are discussed. C1 Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Hickson, ID (reprint author), Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. EM ian.hickson@cancer.org.uk RI Chang, Michael/B-9279-2012; OI Chang, Michael/0000-0002-1706-3337; Bachrati, Csanad Z./0000-0003-1703-5894 FU Intramural NIH HHS; NCI NIH HHS [CA91029, CA97175, P01 CA097175, R01 CA091029] NR 34 TC 172 Z9 180 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2006 VL 103 IS 11 BP 4068 EP 4073 DI 10.1073/pnas.0508295103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 027QE UT WOS:000236429300026 PM 16537486 ER PT J AU Korherr, C Gille, H Schafer, R Koenig-Hoffmann, K Dixelius, J Egland, KA Pastan I Brinkmann, U AF Korherr, C Gille, H Schafer, R Koenig-Hoffmann, K Dixelius, J Egland, KA Pastan, I Brinkmann, U TI Identification of proangiogenic genes and pathways by high-throughput functional genomics: TBK1 and the IRF3 pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; cDNA/libraries; expression cloning; human umbilical vein enclothelial cells; screening ID NF-KAPPA-B; MICROVASCULAR ENDOTHELIAL-CELLS; IFN-REGULATORY FACTOR-3; ANGIOGENESIS; INDUCTION; GROWTH; CANCER; INTERLEUKIN-8; EXPRESSION; RECEPTORS AB A genome-wide phenotype screen was used to identify factors and pathways that induce proliferation of human umbilical vein endothelial cells (HUVEC). HUVEC proliferation is a recognized marker for factors that modulate vascularization. Screening "hits" included known proangiogenic factors, such as VEGF, FGF1, and FGF2 and additional factors for which a direct association with angiogenesis was not previously described. These include the kinase TBK1 as well as Toll-like receptor adaptor molecule and IFN regulatory factor 3. All three proteins belong to one signaling pathway that mediates induction of gene expression, including a mixture of secreted factors, which, in concert, mediate proliferative activity toward endothelial cells. TBK1 as the "trigger" of this pathway is induced under hypoxic conditions and expressed at significant levels in many solid tumors. This pattern of expression and the decreased expression of angiogenic factors in cultured cells upon RNA-interference-mediated ablation suggests that TBK1 is important for vascularization and subsequent tumor growth and a target for cancer therapy. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Karolinska Inst, SE-17177 Stockholm, Sweden. Xantos Biomed AG, D-81377 Munich, Germany. RP Pastan I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bldg 37, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov; efmu.brinkmann@t-online.de FU Intramural NIH HHS NR 29 TC 59 Z9 63 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 14 PY 2006 VL 103 IS 11 BP 4240 EP 4245 DI 10.1073/pnas.0511319103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 027QE UT WOS:000236429300056 PM 16537515 ER PT J AU Song, LS Sobie, EA McCulle, S Lederer, WJ Balke, CW Cheng, HP AF Song, LS Sobie, EA McCulle, S Lederer, WJ Balke, CW Cheng, HP TI Orphaned ryanodine receptors in the failing heart SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium signaling; local control; dyssynchrony; heart failure; transverse tubules ID SARCOPLASMIC-RETICULUM CA2+; RAT VENTRICULAR MYOCYTES; ACTION-POTENTIAL REPOLARIZATION; CARDIAC MYOCYTES; TRANSVERSE TUBULES; CALCIUM TRANSIENTS; T-TUBULES; FAILURE; RELEASE; MUSCLE AB Heart muscle is characterized by a regular array of proteins and structures that form a repeating functional unit identified as the sarcomere. This regular structure enables tight coupling between electrical activity and Ca2+ signaling. In heart failure, multiple cellular defects develop, including reduced contractility, altered Ca2+ signaling, and arrhythmias; however, the underlying causes of these defects are not well understood. Here, in ventricular myocytes from spontaneously hypertensive rats that develop heart failure, we identify fundamental changes in Ca2+ signaling that are related to restructuring of the spatial organization of the cells. Myocytes display both a reduced ability to trigger sarcoplasmic reticulum Ca2+ release and increased spatial dispersion of the transverse tubules (TTs). Remodeled TTs in cells from failing hearts no longer exist in the regularly organized structures found in normal heart cells, instead moving within the sarcomere away from the Vine structures and leaving behind the sarcoplasmic reticulum Ca2+ release channels, the ryanodine receptors (RyRs). These orphaned RyRs appear to be responsible for the dyssynchronous Ca2+ sparks that have been linked to blunted contractility and, probably, Ca2+-dependent arrhythmias in diverse models of heart failure. We conclude that the increased spatial dispersion of the TTs and orphaned RyRs lead to the loss of local control and Ca2+ instability in heart failure. C1 Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Baltimore, MD 21201 USA. NYU, Sch Med, Div Pediat Cardiol, New York, NY 10016 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ Kentucky, Coll Med, Dept Med, Lexington, KY 40506 USA. Univ Kentucky, Coll Med, Dept Physiol, Lexington, KY 40506 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. RP Song, LS (reprint author), Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, Baltimore, MD 21201 USA. EM songl@umbi.umd.edu; cwbalk2@email.uky.edu RI Lederer, William/B-1285-2010; Song, Long-Sheng/D-5899-2012 FU NHLBI NIH HHS [R01 HL076230] NR 56 TC 228 Z9 232 U1 0 U2 16 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 MAR 14 PY 2006 VL 103 IS 11 BP 4305 EP 4310 DI 10.1073/pnas.0509324103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 027QE UT WOS:000236429300067 PM 16537526 ER PT J AU Shalowitz, DI Garrett-Mayer, E Wendler, D AF Shalowitz, DI Garrett-Mayer, E Wendler, D TI The accuracy of surrogate decision makers - A systematic review SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID PATIENTS RESUSCITATION PREFERENCES; HEALTH-CARE DECISIONS; SUBSTITUTED JUDGMENT; TREATMENT CHOICES; LIFE; PROXY; PREDICTIONS; RESIDENTS; AGREEMENT; CONSENT AB Background: Clinicians currently rely on patient-designated and next-of-kin surrogates to make end-of-life treatment decisions for incapacitated patients. Surrogates are instructed to use the substituted judgment standard, which directs them to make the treatment decision that the patient would have made if he or she were capacitated. However, commentators have questioned the accuracy with which surrogates predict patients' treatment preferences. Methods: A systematic literature search was conducted using PubMed, the Cochrane Library, and manuscript references, to identify published studies that provide empirical data on how accurately surrogates predict patients' treatment preferences and on the efficacy of commonly proposed methods to improve surrogate accuracy. Two of us ( D. I. S. and D. W.) reviewed all articles and extracted data on the hypothetical scenarios used to assess surrogate accuracy and the percentage of agreement between patients and surrogates. Results: The search identified 16 eligible studies, involving 151 hypothetical scenarios and 2595 surrogate-patient pairs, which collectively analyzed 19 526 patient-surrogate paired responses. Overall, surrogates predicted patients' treatment preferences with 68% accuracy. Neither patient designation of surrogates nor prior discussion of patients' treatment preferences improved surrogates' predictive accuracy. Conclusions: Patient-designated and next-of-kin surrogates incorrectly predict patients' end-of-life treatment preferences in one third of cases. These data undermine the claim that reliance on surrogates is justified by their ability to predict incapacitated patients' treatment preferences. Future studies should assess whether other mechanisms might predict patients' end-of-life treatment preferences more accurately. Also, they should assess whether reliance on patient-designated and next-of-kin surrogates offers patients and/or their families benefits that are independent of the accuracy of surrogates' decisions. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Div Biostat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov RI Shalowitz, David/A-7432-2009; OI Shalowitz, David/0000-0002-5189-4687 NR 29 TC 349 Z9 353 U1 2 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 13 PY 2006 VL 166 IS 5 BP 493 EP 497 DI 10.1001/archinte.166.5.493 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 022CM UT WOS:000236032300003 PM 16534034 ER PT J AU Furuno, JP McGregor, JC Harris, AD Johnson, JA Johnson, JK Langenberg, P Venezia, RA Finkelstein, J Smith, DL Strauss, SM Perencevich, EN AF Furuno, JP McGregor, JC Harris, AD Johnson, JA Johnson, JK Langenberg, P Venezia, RA Finkelstein, J Smith, DL Strauss, SM Perencevich, EN TI Identifying groups at high risk for carriage of antibiotic-resistant bacteria SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID STAPHYLOCOCCUS-AUREUS; HOSPITALIZED-PATIENTS; PSEUDOMONAS-AERUGINOSA; SURVEILLANCE CULTURES; COST-EFFECTIVENESS; ADMISSION; COLONIZATION; ENTEROCOCCUS; PREVALENCE; INFECTIONS AB Background: No simple, cost-effective methods exist to identify patients at high risk for methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci colonization outside intensive care settings. Without such methods, colonized patients are entering hospitals undetected and transmitting these bacteria to other patients. We aimed to develop a highly sensitive, simple-to-administer prediction rule to identify subpopulations of patients at high risk for colonization on hospital admission. Methods: We conducted a prospective cohort study of adult patients admitted to the general medical and surgical wards of a tertiary-care facility. Data were collected using electronic medical records and an investigator-administered questionnaire. Cultures of anterior nares and the perirectal area were also collected within 48 hours of admission. Results: Among 699 patients who enrolled in this study, 697 underwent nasal cultures; 555, perirectal cultures; and 553, both. Patient self-report of a hospital admission in the previous year was the most sensitive variable in identifying patients colonized with methicillin-resistant Staphylococcus aureus or with either organism ( sensitivity, 76% and 90%, respectively). A prediction rule requiring patients to self-report having received antibiotics and a hospital admission in the previous year would have identified 100% of patients colonized with vancomycin-resistant enterococci. In the high-risk groups defined by the prediction rule, the prevalence of colonization by methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, or either organism were 8.1%, 10.2%, and 15.0%, respectively. Conclusion: Patients with a self-reported previous admission within 1 year may represent a high-risk group for colonization by methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci at hospital admission and should be considered for targeted active surveillance culturing. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Vet Affairs Maryland Hlth Care Syst, Baltimore, MD USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Furuno, JP (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 100 N Greene St,Lower Level, Baltimore, MD 21201 USA. EM jfuruno@epi.umaryland.edu RI McGregor, Jessina/A-7625-2008; Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU NCRR NIH HHS [M01 RR16500]; NIAID NIH HHS [R01 AI60859-01A1, K23 AI01752-01A1] NR 22 TC 64 Z9 64 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 13 PY 2006 VL 166 IS 5 BP 580 EP 585 DI 10.1001/archinte.166.5.580 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 022CM UT WOS:000236032300016 PM 16534047 ER PT J AU Wang, Y Hewitt, SM Liu, S Zhou, X Zhu, H Zhou, C Zhang, G Quan, L Bai, J Xu, N AF Wang, Y Hewitt, SM Liu, S Zhou, X Zhu, H Zhou, C Zhang, G Quan, L Bai, J Xu, N TI Tissue microarray analysis of human FRATI expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours SO BRITISH JOURNAL OF CANCER LA English DT Article DE FRATI; beta-catenin; Wnt pathway; ovarian cancer; tissue microarray ID SQUAMOUS-CELL CARCINOMA; WNT-SIGNALING PATHWAY; CLINICOPATHOLOGICAL FEATURES; MOLECULAR-CLONING; CANCER; AXIN; OVEREXPRESSION; MUTATIONS; GENE; PROTOONCOGENE AB The mechanisms involved in the pathogenesis of ovarian cancer are poorly understood, but evidence suggests that aberrant activation of Wnt/ beta- catenin signalling pathway plays a significant role in this malignancy. However, the molecular defects that contribute to the activation of this pathway have not been elucidated. Frequently rearranged in advanced T- cell lymphomas- 1 ( FRAT1) is a candidate for the regulation of cytoplasmic beta- catenin. In this study, we developed in situ hybridisation probes to evaluate the presence of FRAT1 and used an anti- beta- catenin antibody to evaluate by immunohistochemistry the expression levels and subcellular localisation of b- catenin in ovarian cancer tissue microarrays. Expression of FRAT1 was found in some human normal tissues and 47% of ovarian adenocarcinomas. A total of 46% of ovarian serous adenocarcinomas were positive for FRAT1 expression. Accumulation of beta- catenin in the nucleus and/ or cytoplasm was observed in 55% ovarian adenocarcinomas and in 59% of serous adenocarcinomas. A significant association was observed in ovarian serous adenocarcinomas between FRAT1 and beta- catenin expression ( P < 0.01). These findings support that Wnt/ beta- catenin signalling may be aberrantly activated through FRAT1 overexpression in ovarian serous adenocarcinomas. The mechanism behind the overexpression of FRAT1 in ovarian serous adenocarcinomas and its significance is yet to be investigated. C1 Chinese Acad Med Sci, Lab Cell & Mol Biol, Inst Canc, Beijing 100021, Peoples R China. Chinese Acad Med Sci, Lab Cell & Mol Biol, Canc Hosp, Beijing 100021, Peoples R China. Peking Union Med Coll, Beijing 100021, Peoples R China. NCI, NIH, Tissue Array Res Program, Pathol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. RP Xu, N (reprint author), Chinese Acad Med Sci, Lab Cell & Mol Biol, Inst Canc, Beijing 100021, Peoples R China. EM xningzhi@public.bta.net.cn RI Zhou, Cuiqi/B-1568-2010; Liu, Shuang/J-1798-2012; Zhang, Guo/C-8005-2013 NR 30 TC 23 Z9 25 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 13 PY 2006 VL 94 IS 5 BP 686 EP 691 DI 10.1038/sj.bjc.6602988 PG 6 WC Oncology SC Oncology GA 019WR UT WOS:000235868700013 PM 16479254 ER PT J AU Genkinger, JM Hunter, DJ Spiegelman, D Anderson, KE Buring, JE Freudenheim, JL Goldbohm, RA Harnack, L Hankinson, SE Larsson, SC Leitzmann, M McCullough, ML Marshall, J Miller, AB Rodriguez, C Rohan, TE Schatzkin, A Schouten, LJ Wolk, A Zhang, SM Smith-Warner, SA AF Genkinger, JM Hunter, DJ Spiegelman, D Anderson, KE Buring, JE Freudenheim, JL Goldbohm, RA Harnack, L Hankinson, SE Larsson, SC Leitzmann, M McCullough, ML Marshall, J Miller, AB Rodriguez, C Rohan, TE Schatzkin, A Schouten, LJ Wolk, A Zhang, SM Smith-Warner, SA TI Alcohol intake and ovarian cancer risk: a pooled analysis of 10 cohort studies SO BRITISH JOURNAL OF CANCER LA English DT Article DE alcohol; ovarian cancer; pooled analysis ID FOOD FREQUENCY QUESTIONNAIRE; POSTMENOPAUSAL WOMEN; BREAST-CANCER; CONFIDENCE-INTERVALS; REGRESSION-MODELS; COLORECTAL-CANCER; MEASUREMENT ERROR; DIETARY-FAT; CONSUMPTION; VALIDATION AB Alcohol has been hypothesized to promote ovarian carcinogenesis by its potential to increase circulating levels of estrogen and other hormones; through its oxidation byproduct, acetaldehyde, which may act as a cocarcinogen; and by depletion of folate and other nutrients. Case-control and cohort studies have reported conflicting results relating alcohol intake to ovarian cancer risk. We conducted a pooled analysis of the primary data from ten prospective cohort studies. The analysis included 529 638 women among whom 2001 incident epithelial ovarian cases were documented. After study-specific relative risks ( RR) and 95% confidence intervals ( CI) were calculated by Cox proportional hazards models, and then were pooled using a random effects model; no associations were observed for intakes of total alcohol ( pooled multivariate RR 1.12, 95% CI 0.86-1.44 comparing >= 30 to 0 g day(-1) of alcohol) or alcohol from wine, beer or spirits and ovarian cancer risk. The association with alcohol consumption was not modified by oral contraceptive use, hormone replacement therapy, parity, menopausal status, folate intake, body mass index, or smoking. Associations for endometrioid, mucinous, and serous ovarian cancer were similar to the overall findings. This pooled analysis does not support an association between moderate alcohol intake and ovarian cancer risk. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. TNO, Dept Food & Chem Risk Anal, Zeist, Netherlands. Natl Inst Environm Med, Karolinska Inst, Div Nutr Epidemiol, Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Univ Toronto, Dept Publ Hlth Sci, Fac Med, Toronto, ON, Canada. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Maastricht Univ, NUTRIM, Dept Epidemiol, Maastricht, Netherlands. RP Genkinger, JM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu RI Schouten, Leo/G-3713-2012; Larsson, Susanna/F-6065-2015 OI Larsson, Susanna/0000-0003-0118-0341 FU NCI NIH HHS [P01 CA055075, R25 CA098566, CA 55075, CA 098566] NR 42 TC 28 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 13 PY 2006 VL 94 IS 5 BP 757 EP 762 DI 10.1038/sj.bjc.6603020 PG 6 WC Oncology SC Oncology GA 019WR UT WOS:000235868700024 PM 16495916 ER PT J AU Kruhlak, MJ Celeste, A Dellaire, G Fernandez-Capetillo, O Muller, WG McNally, JG Bazett-Jones, DP Nussenzweig, A AF Kruhlak, MJ Celeste, A Dellaire, G Fernandez-Capetillo, O Muller, WG McNally, JG Bazett-Jones, DP Nussenzweig, A TI Changes in chromatin structure and mobility in living cells at sites of DNA double-strand breaks SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HISTONE H2AX PHOSPHORYLATION; SACCHAROMYCES-CEREVISIAE; GENOMIC INSTABILITY; CORRELATIVE LIGHT; HUMAN-FIBROBLASTS; RAPID EXCHANGE; IN-VIVO; REPAIR; DAMAGE; DYNAMICS AB The repair of DNA double-strand breaks (DSBs) is facilitated by the phosphorylation of H2AX, which organizes DNA damage signaling and chromatin remodeling complexes in the vicinity of the lesion (Pilch, D.R., O.A. Sedelnikova, C. Redon, A. Celeste, A. Nussenzweig, and W. M. Bonner. 2003. Biochem. Cell Biol. 81: 123-129; Morrison, A.J., and X. Shen. 2005. Cell Cycle. 4: 568-571; van Attikum, H., and S.M. Gasser. 2005. Nat. Rev. Mol. Cell. Biol. 6: 757-765). The disruption of DNA integrity induces an alteration of chromatin architecture that has been proposed to activate the DNA damage transducing kinase ataxia telangiectasia mutated (ATM; Bakkenist, C.J., and M.B. Kastan. 2003. Nature. 421: 499-506). However, little is known about the physical properties of damaged chromatin. In this study, we use a photoactivatable version of GFP-tagged histone H2B to examine the mobility and structure of chromatin containing DSBs in living cells. We find that chromatin containing DSBs exhibits limited mobility but undergoes an energy-dependent local expansion immediately after DNA damage. The localized expansion observed in real time corresponds to a 30-40% reduction in the density of chromatin fibers in the vicinity of DSBs, as measured by energy-filtering transmission electron microscopy. The observed opening of chromatin occurs independently of H2AX and ATM. We propose that localized adenosine triphosphate-dependent decondensation of chromatin at DSBs establishes an accessible subnuclear environment that facilitates DNA damage signaling and repair. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol, NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada. RP Kruhlak, MJ (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM kruhlakm@mail.nih.gov; andre_nussenzweig@nih.gov RI Fernandez-Capetillo, Oscar/H-3508-2015 OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885 FU Intramural NIH HHS NR 60 TC 287 Z9 295 U1 2 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 13 PY 2006 VL 172 IS 6 BP 823 EP 834 DI 10.1083/jcb.200510015 PG 12 WC Cell Biology SC Cell Biology GA 021GO UT WOS:000235971900009 PM 16520385 ER PT J AU Scholz, SW Xiromerisiou, G Fung, HC Eerola, J Hellstrom, O Papadimitriou, A Hadjigeorgiou, GM Tienari, PJ Fernandez, HH Mandel, R Okun, MS Gwinn-Hardy, K Singleton, AB AF Scholz, SW Xiromerisiou, G Fung, HC Eerola, J Hellstrom, O Papadimitriou, A Hadjigeorgiou, GM Tienari, PJ Fernandez, HH Mandel, R Okun, MS Gwinn-Hardy, K Singleton, AB TI The human prion gene M129V polymorphism is not associated with idiopathic Parkinson's disease in three distinct populations SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; prion; Creutzfeld-Jakob disease; M129V ID CREUTZFELDT-JAKOB-DISEASE; DJ-1 PARK7; FINNISH AB Coexistence of prion disease and idiopathic Parkinson's disease (TPD) has been previously described. It remains unclear whether this relationship may reflect the high incidence of IPD or whether both prion and IPD share common pathogenetic mechanisms. For this reason, we investigated the genotype distribution of the M129V polymorphism of the human prion gene for association with IPD (controls: n = 398, IPD cases: n =400). No association between genotypes in codon 129 and IPD was detected in three distinct Populations, suggesting that this PRNP polymorphism has no direct influence on the susceptibility to IPD. Published by Elsevier Ireland Ltd. C1 NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. Univ Thessaly, Sch Med, Dept Neurol, Neurogenet Unit, Larisa, Greece. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei 10591, Taiwan. Chang Gung Univ, Coll Med, Taipei 10591, Taiwan. UCL, Reta Lila Weston Inst Neurol Studies, London W1T 4JF, England. Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. Univ Helsinki, Biomedicum Helsinki, Neurosci Program, Helsinki, Finland. Seinajoki Cent Hosp, Dept Neurol, Seinajoki, Finland. Univ Florida, Movement Disorders Ctr, Dept Neurol, Gainesville, FL 32610 USA. Univ Florida, Movement Disorders Ctr, Dept Neurosurg, Gainesville, FL 32610 USA. Univ Florida, Movement Disorders Ctr, Dept Neurosci, Gainesville, FL 32610 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Scholz, SW (reprint author), NIA, Mol Genet Unit, NIH, Bldg 35,Room 1A-1012, Bethesda, MD 20892 USA. EM scholzs@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Tienari, Pentti/A-4893-2012; OI Okun, Michael/0000-0002-6247-9358; Gwinn, Katrina/0000-0002-8277-651X; Scholz, Sonja/0000-0002-6623-0429 NR 12 TC 11 Z9 11 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 MAR 13 PY 2006 VL 395 IS 3 BP 227 EP 229 DI 10.1016/j.neulet.2005.10.081 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 016CH UT WOS:000235597800011 PM 16298483 ER PT J AU Shaul, S Nussinov, R Pupko, T AF Shaul, S Nussinov, R Pupko, T TI Paths of lateral gene transfer of lysyl-aminoacyl-tRNA synthetases with a unique evolutionary transition stage of prokaryotes coding for class I and II varieties by the same organisms SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; PHYLOGENETIC ANALYSIS; BORRELIA-BURGDORFERI; TREPONEMA-PALLIDUM; BACILLUS-SUBTILIS; RECOGNITION; TRANSLATION; SPIROCHETE; CODE AB Background: While the premise that lateral gene transfer (LGT) is a dominant evolutionary force is still in considerable dispute, the case for widespread LGT in the family of aminoacyl-tRNA synthetases (aaRS) is no longer contentious. aaRSs are ancient enzymes, guarding the fidelity of the genetic code. They are clustered in two structurally unrelated classes. Only lysine aminoacyl-tRNA synthetase (LysRS) is found both as a class 1 and a class 2 enzyme (LysRS1-2). Remarkably, in several extant prokaryotes both classes of the enzyme coexist, a unique phenomenon that has yet to receive its due attention. Results: We applied a phylogenetic approach for determining the extent and origin of LGT in prokaryotic LysRS. Reconstructing species trees for Archaea and Bacteria, and inferring that their last common ancestors encoded LysRS1 and LysRS2, respectively, we studied the gains and losses of both classes. A complex pattern of LGT events emerged. In specific groups of organisms LysRS1 was replaced by LysRS2 (and vice versa). In one occasion, within the alpha proteobacteria, a LysRS2 to LysRS1 LGT was followed by reversal to LysRS2. After establishing the most likely LGT paths, we studied the possible origins of the laterally transferred genes. To this end, we reconstructed LysRS gene trees and evaluated the likely origins of the laterally transferred genes. While the sources of LysRS1 LGTs were readily identified, those for LysRS2 remain, for now, uncertain. The replacement of one LysRS by another apparently transits through a stage simultaneously coding for both synthetases, probably conferring a selective advantage to the affected organisms. Conclusion: The family of LysRSs features complex LGT events. The currently available data were sufficient for identifying unambiguously the origins of LysRS1 but not of LysRS2 gene transfers. A selective advantage is suggested to organisms encoding simultaneously LysRS1-2. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Ramat Aviv, Israel. NCI, Frederick Canc Res & Dev Ctr, Canc Res Ctr, Nanobiol Program,SAIC Frederick Inc,Basic Res Pro, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Pupko, T (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. EM sshaul@netvision.net.il; ruthn@ncifcrf.gov; talp@post.tau.ac.il OI Pupko, Tal/0000-0001-9463-2575 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 42 TC 7 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD MAR 12 PY 2006 VL 6 AR 22 DI 10.1186/1471-2148-6-22 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 050YV UT WOS:000238128000001 PM 16529662 ER PT J AU Knipling, L Wolff, J AF Knipling, L Wolff, J TI Direct interaction of Bcl-2 proteins with tubulin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE tubulin; microtubule assembly; Bcl-2; Bid; Bax; Bak; tubulin S; BH3 domain ID MITOCHONDRIAL-MEMBRANES; NEUROBLASTOMA-CELLS; STRUCTURAL-CHANGES; INDUCED APOPTOSIS; BETA-TUBULIN; MICROTUBULE; COLCHICINE; BINDING; POLYMERIZATION; PACLITAXEL AB A direct interaction between tubulin and several pro-apoptotic and anti-apoptotic members of the Bcl-2 family has been demonstrated by effects oil the assembly of microtubules from pure rat brain tubulin. Bcl-2, Bid, and Bad inhibit assembly sub-stoichiometrically, whereas peptides from Bak and Bax promote tubulin polymerization at near stoichiometric concentrations. These opposite effects oil microtubule assembly are mutually antagonistic. The BH3 homology domains, common to all members of the family, are involved in the interaction with tubulin but do not themselves affect polymerization. Pelleting experiments with paclitaxel-stabilized microtubules show that Bak is associated with the microtubule pellet, whereas Bid remains primarily With the unpolymerized fraction. These interactions require the presence of the anionic C-termini of alpha- and beta-tubulin as they do not occur With tubulin S in which the C-termini have been removed. While in no way ruling Out other pathways, such direct associations are the simplest potential regulatory mechanism for apoptosis resulting from disturbances in microtubule or tubulin function. Published by Elsevier Inc. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wolffj@mail.nih.gov NR 46 TC 15 Z9 15 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 10 PY 2006 VL 341 IS 2 BP 433 EP 439 DI 10.1016/j.bbrc.2005.12.201 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 013MW UT WOS:000235414400023 PM 16446153 ER PT J AU Park, YH Lee, BR Seok, YJ Peterkofsky, A AF Park, YH Lee, BR Seok, YJ Peterkofsky, A TI In vitro reconstitution of catabolite repression in Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUGAR PHOSPHOTRANSFERASE SYSTEM; PHOSPHORYL TRANSFER COMPLEX; ADENYLATE-CYCLASE ACTIVITY; CYTOPLASMIC DOMAIN; ENZYME IIA(GLC); PROTEIN; EXPRESSION; MONOPHOSPHATE; PURIFICATION; IIA(GLUCOSE) AB A widely accepted model for catabolite repression posits that phospho-IIA(Glc) of the bacterial phosphotransferase system activates adenylyl cyclase (AC) activity. For many years, attempts to observe such regulatory properties of AC in vitro have been unsuccessful. To further study the regulation, AC was produced fused to the transmembrane segments of the serine chemoreceptor Tsr. Cells harboring Tsr-AC and normal AC, expressed from the cya promoter on a low copy number vector, exhibit similar behavior with respect to elevation of cAMP levels resulting from deletion of crp, expressing the catabolite regulatory protein. Membrane-bound Tsr-AC exhibits activity comparable with the native form of AC. Tsr-AC binds IIA(Glc) specifically, regardless of its phosphorylation state, but not the two general phosphotransferase system proteins, enzyme I and HPr; IIA(Glc) binding is localized to the C-terminal region of AC. Binding to membranes of either dephospho- or phospho-IIA(Glc) has no effect on AC activity. However, in the presence of an Escherichia coli extract, P-IIA(Glc), but not IIA(Glc), stimulates AC activity. Based on these findings of a direct interaction of IIAGlc with AC, but activity regulation only in the presence of E. coli extract, a revised model for AC activity regulation is proposed. C1 Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea. Seoul Natl Univ, Inst Microbiol, Seoul 151742, South Korea. Seowon Univ, Dept Biol, Chongju City 361742, South Korea. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Seok, YJ (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2316,MSC-8017, Bethesda, MD 20814 USA. EM yjseok@plaza.snu.ac.kr; peterkofsky@nih.gov FU Intramural NIH HHS NR 33 TC 65 Z9 68 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 MAR 10 PY 2006 VL 281 IS 10 BP 6448 EP 6454 DI 10.1074/jbc.M512672200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BX UT WOS:000236030800039 PM 16407219 ER PT J AU Makareeva, E Cabral, WA Marini, JC Leikin, S AF Makareeva, E Cabral, WA Marini, JC Leikin, S TI Molecular mechanism of alpha 1(I)-osteogenesis Imperfecta/Ehlers-Danlos syndrome - Unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNDROME TYPE-VII; OSTEOGENESIS-IMPERFECTA; THERMAL-STABILITY; PROCOLLAGEN; PROTEINASE; MUTATIONS; DEFECT; CHAIN; TEMPERATURE; PROPEPTIDE AB We demonstrate that 85 N-terminal amino acids of the alpha 1(I) chain participate in a highly stable folding domain, acting as the stabilizing anchor for the amino end of the type I collagen triple helix. This anchor region is bordered by amicrounfolding region, 15 amino acids in each chain, which include no proline or hydroxyproline residues and contain a chymotrypsin cleavage site. Glycine substitutions and amino acid deletions within the N-anchor domain induce its reversible unfolding above 34 degrees C. The overall triple helix denaturation temperature is reduced by 5 - 6 degrees C, similar to complete N-anchor removal. N-propeptide partially restores the stability of mutant procollagen but not sufficiently to prevent N-anchor unfolding and a conformational change at the N-propeptide cleavage site. The ensuing failure of N-proteinase to cleave at the misfolded site leads to incorporation of pN-collagen into fibrils. Similar, but weaker, effects are caused by G88E substitution in the adjacent triplet, which appears to alter N-anchor structure as well. As in Ehlers-Danlos syndrome (EDS) VIIA/B, fibrils containing pN-collagen are thinner and weaker causing EDS-like laxity of large and small joints and paraspinal ligaments. However, distinct structural consequences of N-anchor destabilization result in a distinct alpha 1( I)osteogenesis imperfecta (OI)/EDS phenotype. C1 NICHD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Leikin, S (reprint author), NICHD, Sect Phys Biochem, NIH, Bldg 9,Rm 1E-127, Bethesda, MD 20892 USA. EM leikins@mail.nih.gov RI Leikin, Sergey/A-5518-2008; Makareeva, Elena/F-5183-2011 OI Leikin, Sergey/0000-0001-7095-0739; NR 26 TC 44 Z9 46 U1 0 U2 3 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 MAR 10 PY 2006 VL 281 IS 10 BP 6463 EP 6470 DI 10.1074/jbc.M511830200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BX UT WOS:000236030800041 PM 16407265 ER PT J AU Piscitelli, CL Angel, BE Bailey, BW Hargrave, P Dratz, EA Lawrence, CM AF Piscitelli, CL Angel, BE Bailey, BW Hargrave, P Dratz, EA Lawrence, CM TI Equilibrium between metarhodopsin-I and metarhodopsin-II is dependent on the conformation of the third cytoplasmic loop SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; X-RAY CRYSTALLOGRAPHY; INITIAL RATE ANALYSIS; TRANSDUCIN ACTIVATION; CRYSTAL-STRUCTURE; ALPHA-SUBUNIT; STRUCTURAL FEATURES; INTRINSIC DISORDER; EXCITED RHODOPSIN; ANTIBODY IMPRINTS AB Rhodopsin is a G-protein-coupled receptor ( GPCR) that is the light detector in the rod cells of the eye. Rhodopsin is the best understood member of the large GPCR superfamily and is the only GPCR for which atomic resolution structures have been determined. However, these structures are for the inactive, dark-adapted form. Characterization of the conformational changes in rhodopsin caused by light-induced activation is of wide importance, because the metarhodopsin-II photoproduct is analogous to the agonist-occupied conformation of other GPCRs, and metarhodopsin-I may be similar to antagonist-occupied GPCR conformations. In this work we characterize the interaction of antibody K42-41L with the metarhodopsin photoproducts. K42-41L is shown to inhibit formation of metarhodopsin-II while it stabilizes the metarhodopsin-I state. Thus, K42-41L recognizes an epitope accessible in dark-adapted rhodopsin and metarhodopsin-I that is lost upon formation of metarhodopsin-II. Previous work has shown that the peptide TGALQERSK is able to mimic the K42-41L epitope, and we have now determined the structure of the K42-41L-peptide complex. The structure demonstrates a central role for elements of the rhodopsin C3 loop, particularly Gln(238) and Glu(239), in the interaction with K42-41L. Geometric constraints taken from the antibody-bound peptide were used to model the epitope on the rhodopsin surface. The resulting model suggests that K42-41L locks the C3 loop into an extended conformation that is intermediate between two compact conformations seen in crystal structures of dark-adapted rhodopsin. Together, the structural and functional data strongly suggest that the equilibrium between metarhodopsin-I and metarhodopsin-II is dependent upon the conformation of the C3 loop. The biological implications of this model and its possible relations to dimeric and multimeric complexes of rhodopsin are discussed. C1 Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. NCI, NIH, Rockville, MD 20852 USA. Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA. RP Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. EM lawrence@chemistry.montana.edu RI Bailey, Brian/B-1732-2009 FU NCRR NIH HHS [P20-RR16455]; NIGMS NIH HHS [R01-GM62547] NR 72 TC 10 Z9 10 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 10 PY 2006 VL 281 IS 10 BP 6813 EP 6825 DI 10.1074/jbc.M510175200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BX UT WOS:000236030800080 PM 16407202 ER PT J AU Islam, A Adamik, B Hawari, FI Ma, G Rouhani, FN Zhang, J Levine, SJ AF Islam, A Adamik, B Hawari, FI Ma, G Rouhani, FN Zhang, J Levine, SJ TI Extracellular TNFR1 release requires the calcium-dependent formation of a nucleobindin 2-ARTS-1 complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; LEUCYL-SPECIFIC AMINOPEPTIDASE; FACTOR-BINDING-PROTEIN; CELL-DERIVED EXOSOMES; KAPPA-B ACTIVATION; FACTOR-ALPHA; MOLECULAR-CLONING; ENDOPLASMIC-RETICULUM; MULTIVESICULAR BODY; RECEPTOR AB Extracellular tumor necrosis factor (TNF) receptors function as TNF-binding proteins that modulate TNF activity. In human vascular endothelial cells ( HUVEC), extracellular TNFR1 ( type I TNF receptor, TNFRSF1A) is generated by two mechanisms, proteolytic cleavage of soluble TNFR1 ectodomains and the release of full-length 55-kDa TNFR1 in the membranes of exosome-like vesicles. TNFR1 release from HUVEC is known to involve the association between ARTS-1 ( aminopeptidase regulator of TNFR1 shedding), an integral membrane aminopeptidase, and TNFR1. The goal of this study was to identify ARTS-1 binding partners that modulate TNFR1 release to the extracellular space. A yeast two-hybrid screen of a human placenta cDNA library showed that NUCB2( nucleobindin 2), via its helix-loop-helix domains, binds the ARTS-1 extracellular domain. The association between endogenous ARTS-1 and NUCB2 in HUVEC was demonstrated by co-immunoprecipitation experiments, which showed the formation of a calcium-dependent NUCB2 . ARTS-1 complex that associated with a subset of total cellular TNFR1. Confocal microscopy experiments demonstrated that this association involved a distinct population of NUCB2-containing intracytoplasmic vesicles. RNA interference was utilized to specifically knock down NUCB2 and ARTS-1 expression, which demonstrated that both are required for the constitutive release of a full-length 55-kDa TNFR1 within exosome-like vesicles as well as the inducible proteolytic cleavage of soluble TNFR1 ectodomains. We propose that calcium-dependent NUCB2 . ARTS-1 complexes, which associate with TNFR1 prior to its commitment to pathways that result in either the constitutive release of TNFR1 exosome-like vesicles or the inducible proteolytic cleavage of TNFR1 ectodomains, play an important role in mediating TNFR1 release to the extracellular compartment. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Rm 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov FU Intramural NIH HHS NR 52 TC 52 Z9 53 U1 1 U2 3 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 MAR 10 PY 2006 VL 281 IS 10 BP 6860 EP 6873 DI 10.1074/jbc.M509397200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BX UT WOS:000236030800084 PM 16407280 ER PT J AU Mattera, R Tsai, YC Weissman, AM Bonifacino, JS AF Mattera, R Tsai, YC Weissman, AM Bonifacino, JS TI The Rab5 guanine nucleotide exchange factor Rabex-5 binds ubiquitin (Ub) and functions as a Ub ligase through an atypical Ub-interacting motif and a zinc finger domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CUE DOMAIN; RECEPTOR ENDOCYTOSIS; PROTEIN; COMPLEX; RABAPTIN-5; FAMILY; VPS9P; A20; IDENTIFICATION; RECOGNITION AB Rabex-5, the mammalian orthologue of yeast Vps9p, is a guanine nucleotide exchange factor for Rab5. Rabex-5 forms a tight complex with Rabaptin-5, a multivalent adaptor protein that also binds to Rab4, Rab5, and to domains present in gamma-adaptins and the Golgi-localized, gamma-ear-containing, ARF-binding proteins ( GGAs). Rabaptin-5 augments the Rabex-5 exchange activity, thus generating GTP-bound, membrane-associated Rab5 that, in turn, binds Rabaptin-5 and stabilizes the Rabex-5 . Rabaptin-5 complex on endosomes. Although the Rabex-5 . Rabaptin-5 complex is critical to the regulation of endosomal fusion, the structural determinants of this interaction are unknown. Likewise, the possible binding and covalent attachment of ubiquitin to Rabex-5, two modifications that are critical to the function of yeast Vps9p in endosomal transport, have not been studied. In this study, we identify the 401 - 462 and 551 - 661 coiled-coils as the regions in Rabex-5 and Rabaptin-5, respectively, that interact with one another. We also demonstrate that Rabex-5 undergoes ubiquitination and binds ubiquitin, though not via its proposed C-terminal CUE-like domain. Instead, the N-terminal region of Rabex-5 ( residues 1 - 76), comprising an A20-like Cys(2)/ Cys(2) zinc finger and an adjacent alpha-helix, is important for ubiquitin binding and ubiquitination. Importantly, we demonstrate that the Rabex-5 zinc finger displays ubiquitin ligase (E3) activity. These observations extend our understanding of the regulation of Rabex-5 by Rabaptin-5. Moreover, the demonstration that Rabex-5 is a ubiquitin ligase that binds ubiquitin and undergoes ubiquitination indicates that its role in endosome fusion may be subject to additional regulation by ubiquitin-dependent modifications. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21702 USA. RP Bonifacino, JS (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. EM juan@helix.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 NR 35 TC 70 Z9 71 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 MAR 10 PY 2006 VL 281 IS 10 BP 6874 EP 6883 DI 10.1074/jbc.M509939200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022BX UT WOS:000236030800085 PM 16407276 ER PT J AU Song, YL Peach, ML Roller, PP Qiu, S Wang, SM Long, YQ AF Song, YL Peach, ML Roller, PP Qiu, S Wang, SM Long, YQ TI Discovery of a novel nonphosphorylated pentapeptide motif displaying high affinity for Grb2-SH2 domain by the utilization of 3 '-substituted tyrosine derivatives SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CYCLIC PEPTIDE ANTAGONISTS; STRUCTURE-BASED DESIGN; L-DOPA DERIVATIVES; SH2 DOMAIN; SIGNAL-TRANSDUCTION; BINDING AFFINITY; STRUCTURAL BASIS; BREAST-CANCER; INHIBITORS; SPECIFICITY AB The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. An impressive number of synthetic Grb2-SH2 domain inhibitors have been identified; however, clinical agents operating by this mechanism are lacking, due in part to the unique requirement of anionic phosphate-mimicking functionality for high SH2 domain-binding affinity or the extended peptide nature of most inhibitors. In the current study, a new binding motif was successfully developed by the incorporation of 3'-substituted tyrosine derivatives into a simplified nonphosphorylated cyclic pentapeptide scaffold (4), which resulted in high affinity Grb2-SH2 inhibitors without any phosphotyrosine or phosphotyrosine mimetics. The new L-amino acid analogues hearing an additional nitro, amino, hydroxy, methoxy or carboxy group at the 3'-position of the phenol ring of tyrosine were prepared in an orthogonally protected form suitable for solid-phase peptide synthesis using Fmoc protocols. The incorporation of these residues into cyclic peptides composed of a five-amino acid sequence motif, Xx(1)-Leu-(3'-substituted-Tyr)-Ac6c-Asn, provided a brand new class of nonphosphorylated Grb2 SH2 domain inhibitors with reduced size, charge and peptidic character. The highest binding affinity was exhibited by the 3'-aminotyrosine (3'-NH2-Tyr)-containing (R)-sulfoxide-cyclized pentapeptide (10b) with an IC50 = 58 nM, the first example with low-nanomolar affinity for a five-amino acid long sequence binding to Grb2-SH2 domain free of any phosphotyrosine or phosphotyrosine mimics. However, the incorporation of 3'-NO2-Tyr, 3'-OH-Tyr or 3'-OCH3-Tyr surrogates in the pentapeptide scaffold is detrimental to Grb2-SH2 binding. These observations were rationalized using molecular modeling. More significantly, the best Grb2-SH2 inhibitor 10b showed excellent activity in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with an IC50 value of 19 nM. This study is the first attempt to identify novel nonphosphorylated high affinity Grb2 SH2 inhibitors by the utilization of 3'-substituted tyrosine derivatives, providing a promising new strategy and template for the development of non-pTyr-containing Grb2-SH2 domain antagonists with potent cellular activity, which potentially may find value in chemical therapeutics for erbB2-related cancers. C1 Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Inst Biol Sci,Grad Sch, Shanghai 201203, Peoples R China. NCI Frederick, SAIC, Basic Res Program, Ft Detrick, MD 21702 USA. NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Dept Med Chem, Ann Arbor, MI 48109 USA. RP Long, YQ (reprint author), Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Inst Biol Sci,Grad Sch, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China. EM yqlong@mail.shcnc.ac.cn RI Wang, Shaomeng/E-9686-2010 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 33 TC 31 Z9 34 U1 3 U2 13 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 MAR 9 PY 2006 VL 49 IS 5 BP 1585 EP 1596 DI 10.1021/jm050910x PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 021SJ UT WOS:000236005400011 PM 16509576 ER PT J AU Greiner, E Boos, TL Prisinzano, TE De Martino, MG Zeglis, B Dersch, CM Marcus, J Partilla, JS Rothman, RB Jacobson, AE Rice, KC AF Greiner, E Boos, TL Prisinzano, TE De Martino, MG Zeglis, B Dersch, CM Marcus, J Partilla, JS Rothman, RB Jacobson, AE Rice, KC TI Design and synthesis of promiscuous high-affinity monoamine transporter ligands: Unraveling transporter selectivity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIOGENIC-AMINE TRANSPORTERS; ABUSE THERAPEUTIC AGENTS; COCAINE-ABUSE; DOPAMINE-TRANSPORTER; NOREPINEPHRINE TRANSPORTER; ANALOGS; INHIBITORS; RESPONSIVENESS; DERIVATIVES; MECHANISMS AB A series of 4- [2-[bis(4-fluorophenyl)methoxy]ethyl]-piperidines and 4-[2-[(bisphenyl)methoxy] ethyl] piperidines with different types of substituents in the phenylpropyl side-chain were synthesized and examined for their ability to bind to the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET). All of the compounds showed high binding affinities for the DAT in the low to subnanomolar range. Their ability to bind to the SERT and the NET, while maintaining their high affinity for the DAT, could be altered by substitution in positions C2 and C3 of the phenylpropyl side-chain. This approach gave rise to a new set of compounds with selectivity for the DAT, the DAT and the SERT, or the DAT and the NET. Six compounds (7, 9, 11, 12, 14, and 20) with relatively low SERT/DAT ratios were selected for additional study in biogenic amine uptake inhibition assays based on the biogenic amine transporter binding results. Some of the new ligands can serve as pharmacological tools to block DAT or DAT and another transporter simultaneously. C1 NIDDK, Med Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, NIH,DHHS, Baltimore, MD 21224 USA. Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. Univ Roma La Sapienza, Fac Pharm, Dept Pharmaceut Studies, I-00185 Rome, Italy. RP Rice, KC (reprint author), NIDDK, Med Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM kr21f@nih.gov RI Prisinzano, Thomas/B-7877-2010 FU Intramural NIH HHS NR 37 TC 13 Z9 14 U1 2 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 MAR 9 PY 2006 VL 49 IS 5 BP 1766 EP 1772 DI 10.1021/jm050766f PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 021SJ UT WOS:000236005400026 PM 16509591 ER PT J AU Parker, HG Kruglyak, L Ostrander, EA AF Parker, HG Kruglyak, L Ostrander, EA TI DNA analysis of a putative dog clone SO NATURE LA English DT Letter ID RADIATION HYBRID MAP; JAN 20 2006; CANINE GENOME; RETRACTED SEE; PG 335; ARTICLE; CELLS C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA. Princeton Univ, Dept Ecol & Evolutionary Biol, Carl Icahn Lab, Princeton, NJ 08544 USA. RP Parker, HG (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov RI Parker, Heidi/C-6954-2008 FU Intramural NIH HHS [Z99 HG999999] NR 10 TC 18 Z9 18 U1 0 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 9 PY 2006 VL 440 IS 7081 BP E1 EP E2 DI 10.1038/nature04685 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 019MC UT WOS:000235839500034 PM 16525421 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Hepatitis B - Preventable and now treatable SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ADEFOVIR DIPIVOXIL; LAMIVUDINE; COMBINATION; RESISTANT; DISEASE C1 NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NR 16 TC 22 Z9 26 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 9 PY 2006 VL 354 IS 10 BP 1074 EP 1076 DI 10.1056/NEJMe058309 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 019FY UT WOS:000235822200013 PM 16525145 ER PT J AU Jeong, J Berman, P Przytycka, T AF Jeong, J Berman, P Przytycka, T TI Fold classification based on secondary structure - how much is gained by including loop topology? SO BMC STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN-STRUCTURE ALIGNMENT; DATA-BANK; RECOGNITION; PREDICTION; MOTIFS; SIMILARITIES; SEQUENCES; HAIRPINS AB Background: It has been proposed that secondary structure information can be used to classify ( to some extend) protein folds. Since this method utilizes very limited information about the protein structure, it is not surprising that it has a higher error rate than the approaches that use full 3D fold description. On the other hand, the comparing of 3D protein structures is computing intensive. This raises the question to what extend the error rate can be decreased with each new source of information, especially if the new information can still be used with simple alignment algorithms. We consider the question whether the information about closed loops can improve the accuracy of this approach. While the answer appears to be obvious, we had to overcome two challenges. First, how to code and to compare topological information in such a way that local alignment of strings will properly identify similar structures. Second, how to properly measure the effect of new information in a large data sample. We investigate alternative ways of computing and presenting this information. Results: We used the set of beta proteins with at most 30% pairwise identity to test the approach; local alignment scores were used to build a tree of clusters which was evaluated using a new log-odd cluster scoring function. In particular, we derive a closed formula for the probability of obtaining a given score by chance. Parameters of local alignment function were optimized using a genetic algorithm. Of 81 folds that had more than one representative in our data set, log-odds scores registered significantly better clustering in 27 cases and significantly worse in 6 cases, and small differences in the remaining cases. Various notions of the significant change or average change were considered and tried, and the results were all pointing in the same direction. Conclusion: We found that, on average, properly presented information about the loop topology improves noticeably the accuracy of the method but the benefits vary between fold families as measured by log-odds cluster score. C1 Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Jeong, J (reprint author), Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. EM jijeong@cse.psu.edu; berman@cse.psu.edu; przytyck@ncbi.nlm.nih.gov FU Intramural NIH HHS; NHGRI NIH HHS [HG02238, R01 HG002238] NR 35 TC 4 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6807 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD MAR 8 PY 2006 VL 6 AR 3 DI 10.1186/1472-6807-6-3 PG 10 WC Biophysics SC Biophysics GA 032NZ UT WOS:000236782600001 PM 16524467 ER PT J AU Martomo, SA Yang, WW Vaisman, A Maas, A Yokoi, M Hoeijmakers, JH Hanaoka, F Woodgate, R Gearhart, PJ AF Martomo, SA Yang, WW Vaisman, A Maas, A Yokoi, M Hoeijmakers, JH Hanaoka, F Woodgate, R Gearhart, PJ TI Normal hypermutation in antibody genes from congenic mice defective for DNA polymerase SO DNA REPAIR LA English DT Article DE immunoglobulins; somatic hypermutation; class switch recombination; Pol iota; Pol eta; congenic mice ID CLASS-SWITCH RECOMBINATION; AFFECT SOMATIC HYPERMUTATION; SINGLE-STRANDED-DNA; IMMUNOGLOBULIN GENES; NONTRANSCRIBED STRAND; DEFICIENT MICE; CELL-LINE; IG GENES; ETA; AID AB Several low fidelity DNA polymerases participate in generating mutations in immunoglobulin genes. Polymerase eta is clearly involved in the process by causing substitutions of A:T base pairs, whereas polymerase iota has a controversial role. Although the frequency of mutations was decreased in the BL2 cell line deficient for polymerase iota, hypermutation was normal in the 129 strain of mice, which has a natural nonsense mutation in the Poli gene. It is possible that the mice compensated for the defect over time, or that polymerase eta substituted in the absence of polymerase iota. To examine polymerase iota in a genetically defined background, we backcrossed the 129 nonsense mutation to the C57BL/6 strain for six generations. Class switch recombination and hypermutation were studied in these mice and in congenic mice doubly deficient for both polymerases iota and eta. The absence of both polymerases did not affect production of IgG1, indicating that these enzymes are not involved in switch recombination. poli(-/-F6) mice had the same types of nucleotide substitutions in variable genes as their C57BL/6 counterparts, and mice doubly deficient for polymeraseS iota and eta had the same mutational spectrum as Polh(-/-) mice. Thus, polymerase iota did not contribute to the mutational spectra, even in the absence of polymerase eta. Published by Elsevier B.V. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan. Erasmus Med Ctr, Ctr Biomed Genet, MGC Dept Cell Biol & Genet, Rotterdam, Netherlands. Japan Sci & Technol Agcy, Solut Oriented Res Sci & Technol, Wako, Saitama, Japan. RIKEN, Discovery Res Inst, Wako, Saitama 35101, Japan. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov RI Vaisman, Alexandra/C-3766-2013 OI Vaisman, Alexandra/0000-0002-2521-1467 FU Intramural NIH HHS NR 42 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 7 PY 2006 VL 5 IS 3 BP 392 EP 398 DI 10.1016/j.dnarep.2005.12.006 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 022QG UT WOS:000236070100011 PM 16443401 ER PT J AU Ambudkar, SV Kim, IW Peng, X Sauna, Z FitzGerald, P Xia, D Nandigama, K AF Ambudkar, SV Kim, IW Peng, X Sauna, Z FitzGerald, P Xia, D Nandigama, K TI A conserved aromatic residue 25 amino acids upstream of the Walker A motif in ATP-binding cassette constitutes a subdomain, A-loop, which is critical for ATP-binding in ABC transporters SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Natl Canc Inst, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1369 EP A1369 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205021 ER PT J AU Berglund, ED Ayala, J James, F Bracy, D Jewell, M Powers, AC Wasserman, D AF Berglund, ED Ayala, J James, F Bracy, D Jewell, M Powers, AC Wasserman, D TI Insulin secretory response in conscious FVB/NJ and DBA/2J mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Vanderbilt Univ, Nashville, TN 37029 USA. Mouse Metab Phenotyping Ctr, Nashville, TN 37209 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1282 EP A1282 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204122 ER PT J AU Cao, HP Polansky, MM Blackshear, PJ Anderson, RA AF Cao, HP Polansky, MM Blackshear, PJ Anderson, RA TI Insulin and cinnamon polyphenols increase the amount of insulin receptor b, glucose transporter 4, and anti-inflammatory protein tristetraprolin in mouse 3T3-L1 adipocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 USDA ARS, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA. NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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 MAR 7 PY 2006 VL 20 IS 5 BP A939 EP A939 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201061 ER PT J AU Chatterjie, N Alexander, GJ Stables, JP Murphree, LJ Wang, H AF Chatterjie, N Alexander, GJ Stables, JP Murphree, LJ Wang, H TI Testosterone valproate; a new synthetic steroid SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. NINDS, Anticonvulsant Screening Program, Rockville, MD 20852 USA. NINDS, SRI Int, Fairfax, VA 22033 USA. CUNY Coll Staten Isl, Dept Chem, Staten Isl, NY 10314 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A970 EP A970 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201208 ER PT J AU Citterio, C Jones, H Pacheco-Rodriguez, G Moss, J Vaughan, M AF Citterio, C Jones, H Pacheco-Rodriguez, G Moss, J Vaughan, M TI Effect of 8-Bromo-cAMP on accumulation of brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) in the HepG2 cell nucleus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1375 EP A1375 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205051 ER PT J AU Cox, AD Madigan, JP Fiordalisi, JJ Der, CJ Berzat, AC Philips, MR Bivona, T Ahearn, I Quatela, S Capell, BC Erdos, MR Gordon, LB Varga, R Collins, FS AF Cox, AD Madigan, JP Fiordalisi, JJ Der, CJ Berzat, AC Philips, MR Bivona, T Ahearn, I Quatela, S Capell, BC Erdos, MR Gordon, LB Varga, R Collins, FS TI Farnesylated proteins: how do they get to where they need to go, and how does location regulate their ability to control proliferation, death, transformation and aging? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ N Carolina, Chapel Hill, NC 27599 USA. NYU, New York, NY 10016 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A852 EP A852 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200163 ER PT J AU DeLozier, TC Dai, D Coulter, SJ Bradbury, JA Elizabeth, MY Zeldin, DC Goldstein, JA AF DeLozier, TC Dai, D Coulter, SJ Bradbury, JA Elizabeth, MY Zeldin, DC Goldstein, JA TI Detection of human CYP2Cs in heart, aorta and coronary tissues SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2006 VL 20 IS 5 BP A1111 EP A1112 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202325 ER PT J AU Eisenhofer, G Sharabi, Y Saleem, A Pechnik, S Holmes, C Goldstein, DS AF Eisenhofer, G Sharabi, Y Saleem, A Pechnik, S Holmes, C Goldstein, DS TI Sympathoadrenal function in patients with paroxysmal hypertension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1184 EP A1184 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326203169 ER PT J AU Gallazzini, M Ferraris, JD Burg, MB AF Gallazzini, M Ferraris, JD Burg, MB TI Role of neuropathy target esterase (NTE) in high NaCl-induced accumulation of glycerophosphocholine (GPC) by mouse inner medullary collecting duct 3 (mIMCD3) cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. RI Gallazzini, Morgan/E-5465-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2006 VL 20 IS 5 BP A837 EP A837 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200092 ER PT J AU Goldstein, DS Eldadah, B Holmes, C Pechnik, S Moak, J Saleem, A Sharabi, Y AF Goldstein, DS Eldadah, B Holmes, C Pechnik, S Moak, J Saleem, A Sharabi, Y TI Sympathetic noradrenergic denervation in Parkinson disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1418 EP A1419 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205249 ER PT J AU Hall, KD AF Hall, KD TI Computational biology of in vivo human energy metabolism during semi-starvation and re-feeding SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut C1 NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RI Hall, Kevin/F-2383-2010 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1300 EP A1300 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204204 ER PT J AU Hall, T Vargason, J Burgyan, J AF Hall, T Vargason, J Burgyan, J TI Structure and function of RNA silencing suppressors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. Ctr Agr Biotechnol, H-2101 Godollo, Hungary. RI Burgyan, Jozsef/C-7511-2012 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1309 EP A1309 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204247 ER PT J AU Hatae, N Aksentijevich, N Tomic, M Stojilkovic, SS AF Hatae, N Aksentijevich, N Tomic, M Stojilkovic, SS TI Cloning and functional identification of a novel rat endothelin receptor type A isoform SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NICHD, Sect Cellular Signaling, ERRB, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A918 EP A918 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200474 ER PT J AU Hozumi, K Suzuki, N Nomizu, M Nielsen, P Yamada, Y AF Hozumi, K Suzuki, N Nomizu, M Nielsen, P Yamada, Y TI Active sites of the laminin alphal chain LG4 module for syndecan binding and cell adhesion and spreading SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Tokyo Univ Pharm & Life Sci, Fac Pharm, Hachioji, Tokyo 1920392, Japan. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1097 EP A1097 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202262 ER PT J AU Hui, JX Jiang, JK Thomas, C Yang, W Jacobson, KA Spiegel, AM AF Hui, JX Jiang, JK Thomas, C Yang, W Jacobson, KA Spiegel, AM TI Different effects of 3 negative allosteric modulators of G-protein coupled human Ca2+receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDCD, Mol Pathophysiol Sect, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1119 EP A1119 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202359 ER PT J AU Irarrazabal, CE Burg, MB Ferraris, JD AF Irarrazabal, CE Burg, MB Ferraris, JD TI PI3K Class IB is a negative regulator of the activation by high NaCl of the osmoprotective transcription factor TonEBP/OREBP. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A824 EP A824 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200030 ER PT J AU Jiang, YH Stojilkovic, SS AF Jiang, YH Stojilkovic, SS TI Molecular cloning and characterization of alpha 1-soluble guanylyl cyclase gene promoter in rat pituitary cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NICHD, Sect Cellular Signaling, ERRB, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1340 EP A1340 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204390 ER PT J AU Kraemer, SM Aggarwal, G Springer, A Nelson, S Trimnell, A Smith, L Wang, W Levin, E Flamoe, E Su, XZ Awadalla, P Myler, P Smith, JD AF Kraemer, SM Aggarwal, G Springer, A Nelson, S Trimnell, A Smith, L Wang, W Levin, E Flamoe, E Su, XZ Awadalla, P Myler, P Smith, JD TI Unique patterns of recombination shape var gene structures and repertoires in P-falciparum SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Seattle Biomed Res Inst, Seattle, WA 98109 USA. NIAID, Rockville, MD 20850 USA. N Carolina State Univ, Raleigh, NC 27695 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A909 EP A909 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200431 ER PT J AU Krepkiy, D Yeliseev, A Gawrisch, K AF Krepkiy, D Yeliseev, A Gawrisch, K TI Towards NMR structural studies on the peripheral cannabinoid receptor CB2 in micellar solution. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAAA, NIH, Rockville, MD 20852 USA. RI Yeliseev, Alexei/B-3143-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2006 VL 20 IS 5 BP A920 EP A920 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200481 ER PT J AU Lin, YH Shah, S Salem, N AF Lin, YH Shah, S Salem, N TI Decreased essential fatty acid metabolism in DHA-fed rats: A stable isotope study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIH, Jr Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. 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PD MAR 7 PY 2006 VL 20 IS 5 BP A1347 EP A1347 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204425 ER PT J AU Lo, CWY Rosenthal, J Leatherbury, L Schramm, C Mangal, V Shen, Y Pappas, M Yu, Q AF Lo, CWY Rosenthal, J Leatherbury, L Schramm, C Mangal, V Shen, Y Pappas, M Yu, Q TI High throughput anatomic screening for structural heart defects in chemically mutagenized mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Natl Heart Lung Blood Inst, Lab Dev Biol, NIH, Bethesda, MD 20892 USA. 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NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A923 EP A924 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200499 ER PT J AU Masson, MJ Chung, CJ Peterson, R Graf, ML Ambroso, JL Krull, DL Sciarrotta, J Qualls, W Pohl, LR AF Masson, MJ Chung, CJ Peterson, R Graf, ML Ambroso, JL Krull, DL Sciarrotta, J Qualls, W Pohl, LR TI Inhibition of the adaptive immune response following drug-induced liver SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, MCT, LMI, NIH,DHHS, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. 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NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1238 EP A1238 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326203410 ER PT J AU Moaddel, R Bighi, F Yamaguchi, R Patel, S Wainer, IW AF Moaddel, R Bighi, F Yamaguchi, R Patel, S Wainer, IW TI Development of an immobilized mutant organic cation transporter column for on-line screening using chromatographic techniques SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 20874 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1142 EP A1142 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202466 ER PT J AU Moon, KH AF Moon, KH TI Identification of oxidized and S-nitrosylated mitochondrial proteins in alcohol-exposed rat liver SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1370 EP A1370 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205025 ER PT J AU Notario, PM Heredia, R Meyer, C Balko, N Notari, L Becerra, SP AF Notario, PM Heredia, R Meyer, C Balko, N Notari, L Becerra, SP TI Characterization of pigment epithelium-derived factor receptor (PEDF-R) using bioinformatics tools SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Georgetown Univ, Washington, DC 20057 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A928 EP A928 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201007 ER PT J AU Patterson, BH Wastney, ME Combs, GF Patterson, KY Veillon, C Taylor, PR Levander, OA AF Patterson, BH Wastney, ME Combs, GF Patterson, KY Veillon, C Taylor, PR Levander, OA TI Selenium metabolism in humans: Response of kinetic pools in plasma to 2 yr of Se supplementation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, Biometry Res Grp, EPN, Bethesda, MD 20892 USA. Metab Modeling Svcs Ltd, Hamilton 2030, New Zealand. Cornell Univ, Ithaca, NY 14853 USA. USDA, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. Beltsville Human Nutr Res Ctr, USDA, BARC W, Beltsville, MD 20705 USA. NCI, DCEG, EPS, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1069 EP A1069 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202135 ER PT J AU Paul, BD Buchholz, DR Fu, LZ Shi, YB AF Paul, BD Buchholz, DR Fu, LZ Shi, YB TI An essential role of the Steroid receptor coactivator-p300 pathway in thyroid hormone receptor mediated metamorphosis in Xenopus laevis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A966 EP A967 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201193 ER PT J AU Phillips, RS Holtermann, G Miles, EW Goody, R AF Phillips, RS Holtermann, G Miles, EW Goody, R TI Hydrostatic pressure as a structural and mechanistic probe of tryptophan synthase and tryptophan indole-lyase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Georgia, Athens, GA 30602 USA. Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A903 EP A903 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200400 ER PT J AU Sauna, ZE Nandigama, K Ambudkar, SV AF Sauna, ZE Nandigama, K Ambudkar, SV TI Exploiting enzymatic transition states of the ATPase reaction to elucidate the mechanism of transport by P-glycoprotein (ABCB1) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1367 EP A1368 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205014 ER PT J AU Sheridan, PA Carlson, BA Hatfeild, DL Beck, MA AF Sheridan, PA Carlson, BA Hatfeild, DL Beck, MA TI Decreased selenoprotein expression results in an altered immune response post influenza virus infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut C1 Univ N Carolina, MHRB, Chapel Hill, NC 27599 USA. NCI, Mol Biol Selenium, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1067 EP A1067 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202126 ER PT J AU Shibata, H Nakamura, N Mori, C AF Shibata, H Nakamura, N Mori, C TI Gene expression pattern of spermatogenic cell-specific type 1 hexokinase splicing variants in mouse spermatogenic cells microdissected by laser caputure microdissection (LCM) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Chiba Univ, Dept Bioenv Med, Grad Sch Med, Chuo Ku, Chiba 2608670, Japan. NIEHS, GBS, LRDT, NIH, Res Triangle Pk, NC 27709 USA. Chiba Univ, Ctr Environm Hlth & Field Sci, Kashiwa, Chiba 2770882, Japan. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A883 EP A883 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200306 ER PT J AU Simonds, WF Zhang, JH Jacob, LP Min, KT AF Simonds, WF Zhang, JH Jacob, LP Min, KT TI Conserved role for G protein beta 5/R7 complexes in the regulation of reactive oxygen species and defense of neurons against oxidative stress SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A917 EP A917 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200470 ER PT J AU Storz, G Kawano, M Opdyke, JA Fozo, EM Zhang, AX AF Storz, G Kawano, M Opdyke, JA Fozo, EM Zhang, AX TI Versatile roles of noncoding RNA regulators in bacteria SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NICHD, Cell Biol & Metab Brach, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1309 EP A1309 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204245 ER PT J AU Tan, XLC Fan, F Hoffman, V Longo, NS Lipsky, PE AF Tan, XLC Fan, F Hoffman, V Longo, NS Lipsky, PE TI Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordii Hook F on nephritis in NZB/W F1 mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2006 VL 20 IS 5 BP A1147 EP A1147 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326203002 ER PT J AU Tanaka, M Chock, B Stadtman, E AF Tanaka, M Chock, B Stadtman, E TI mRNA oxidation and its effect on translational expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, Lab Biochem, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1372 EP A1373 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205039 ER PT J AU Tuo, J Bojanowski, CM Shen, DF Zhou, M Ross, RJ Chan, CC AF Tuo, J Bojanowski, CM Shen, DF Zhou, M Ross, RJ Chan, CC TI Development of retinal degeneration in adult CCL2/CX3CR1 deficient mice: a model of age-related macular degeneration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAR 7 PY 2006 VL 20 IS 5 BP A1324 EP A1324 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204315 ER PT J AU White, KK Wilson, C Belloni, DR Booker, J Silverman, LM Gardner, KL Tsongalis, GJ Bowser, R Coleman, WB AF White, KK Wilson, C Belloni, DR Booker, J Silverman, LM Gardner, KL Tsongalis, GJ Bowser, R Coleman, WB TI A novel +ACA BRCA1 promoter polymorphism creates a binding site for the FAC1 transcriptional repressor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03756 USA. Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1324 EP A1325 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204318 ER PT J AU Wilson, SH AF Wilson, SH TI Strategic regulation of excision repair through structural and chemical biology SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1334 EP A1334 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326204359 ER PT J AU Wolff, EC Park, JH Kim, YS Aravind, L Kaevel, J Kang, KR Park, MH AF Wolff, EC Park, JH Kim, YS Aravind, L Kaevel, J Kang, KR Park, MH TI Deoxyhypusine hydroxylase: a novel HEAT-repeat-containing metalloenzyme SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDCR, OPCB, NIH, Bethesda, MD 20892 USA. NCBI, Natl Lib Med, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A902 EP A903 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200399 ER PT J AU Wood, SK Harris, EM Rice, KC Woods, JH AF Wood, SK Harris, EM Rice, KC Woods, JH TI A rodent model of syncope: The effects of a CRH antagonist SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIDDK, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1109 EP A1110 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326202317 ER PT J AU Yan, ZH Liang, ZD Obsil, T Stojilkovic, SS AF Yan, ZH Liang, ZD Obsil, T Stojilkovic, SS TI Role of Lys313-Ile333 ectodomain sequence in P2X4 receptor activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NICHD, ERRB, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1367 EP A1367 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326205010 ER PT J AU Yim, JE Heshka, S Albu, J Heymsfield, S Kuznia, P Harris, T Gallagher, D AF Yim, JE Heshka, S Albu, J Heymsfield, S Kuznia, P Harris, T Gallagher, D TI Independent association of intermuscular adipose tissue with CVD risk factors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Columbia Univ, St Lukes Roosevelt Hosp, Inst Human Nutr, Obes Res Ctr, New York, NY 10025 USA. NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1036 EP A1037 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326201511 ER PT J AU Yu, MJ Pisitkun, T Knepper, MA AF Yu, MJ Pisitkun, T Knepper, MA TI Mass spectrometric identification of apical membrane proteins from perfusion-biotinylated rat kidney inner medullary collecting ducts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A1220 EP A1220 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326203328 ER PT J AU Zhou, XM Ferraris, JD Burg, MB AF Zhou, XM Ferraris, JD Burg, MB TI Involvement of p38 in the contribution of reactive oxygen species (ROS) to high NaCl-dependent activation of the transcription factor TonEBP/OREBP. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2006 VL 20 IS 5 BP A837 EP A837 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 026GA UT WOS:000236326200093 ER PT J AU Giri, J McDermott, MM Greenland, P Guralnik, JM Criqui, MH Liu, K Ferrucci, L Green, D Schneider, JR Tian, L AF Giri, J McDermott, MM Greenland, P Guralnik, JM Criqui, MH Liu, K Ferrucci, L Green, D Schneider, JR Tian, L TI Statin use and functional decline in patients with and without peripheral arterial disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; CHRONIC HEART-FAILURE; ANKLE BRACHIAL INDEX; HYPERCHOLESTEROLEMIC PATIENTS; REDUCTASE INHIBITORS; INTERMITTENT CLAUDICATION; SUBSEQUENT DISABILITY; CIRCULATING MONOCYTES; TREADMILL WALKING; LONGITUDINAL DATA AB OBJECTIVES We determined whether statin use (vs. non-use) is associated with less annual decline in lower-extremity functioning in patients with and without lower-extremity peripheral arterial disease (PAD) over three-year follow-up. BACKGROUND It is unclear whether statin use is associated with less functional decline in patients with PAD. METHODS Participants included 332 men and women with an ankle brachial index (ABI) < 0.90 and 212 with ABI 0.90 to 1.50. Functional outcomes included 6-min walk distance and usual and rapid-pace 4-m walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for five repeated chair rises into an ordinal score ranging from 0 to 12 (12 = best). RESULTS Adjusting for age, race, gender, comorbidities, education, health insurance, total cholesterol/high-density lipoprotein level, body mass index, pack-years of smoking, leg symptoms, immediately previous year functioning, statin use/non-use, ABI, and change in ABI, the PAD participants using statins had less annual decline in usual-pace walking velocity (0.002 vs. -0.024 m/s/year, p = 0.013), rapid-pace walking velocity (-0.006 vs. -0.042 m/s/year, p = 0.006), 6-min walk performance (-34.5 vs. -57.9 feet/year, p = 0.088), and the summary performance score (-0.152 vs. -0.376, p = 0.067) compared with non-users. These associations were attenuated slightly by additional adjustment for high-sensitivity C-reactive protein levels. Among non-PAD participants, there were no significant associations between statin use and functional decline. CONCLUSIONS The PAD patients on statins have less annual decline in lower-extremity performance than PAD patients who are not taking statins. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA. Evanston Northwestern Hosp, Evansville, IN USA. RP McDermott, MM (reprint author), 676 N St Clair,Suite 200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL58099, R01-HL64739] NR 43 TC 53 Z9 54 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 7 PY 2006 VL 47 IS 5 BP 998 EP 1004 DI 10.1016/j.jacc.2005.10.052 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 018TN UT WOS:000235787800013 PM 16516084 ER PT J AU Lakatta, EG Chantler, PD AF Lakatta, EG Chantler, PD TI Payments for debts associated with exercise can become higher as we age and limit exercise capacity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID POSTEXERCISE OXYGEN-CONSUMPTION; MUSCLE; WOMEN AB When one considers the oxygen cost of exercise, the body's rate of oxygen consumption (VO2) in excess of that in the basal state while the exercise is being performed initially comes to mind. But Woo et al. (1), in a paper appearing in this issue of the journal, remind us that for several minutes after an acute bout of exercise, the body continues to consume oxygen at a rate in excess of the basal rate. This continued increased VO2 during recovery from exercise, sometimes referred to as an "oxygen debt," when expressed relative to work performed during the exercise, can range from 14% to 21% of the total VO2 associated with the performance of and recovery from exercise. The "O-2 debt", paid during recovery from exercise, often has not been factored into estimates of exercise efficiency (calories expended for work performed) and reduces efficiency, because it contributes to the total O-2 cost associated with the exercise but contributes no external work. C1 NIA, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov NR 12 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 7 PY 2006 VL 47 IS 5 BP 1058 EP 1059 DI 10.1016/j.jacc.2005.11.039 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 018TN UT WOS:000235787800022 PM 16516093 ER PT J AU Bukh, J Purcell, RH AF Bukh, J Purcell, RH TI A milestone for hepatitis C virus research: A virus generated in cell culture is fully viable in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID EFFICIENT REPLICATION; GENOTYPE 2A; CDNA-CLONE; INFECTION; RNA; ENHANCEMENT; TRANSCRIPTS; CHIMPANZEE; MUTATIONS; LIVER C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Hvidovre Univ Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jbukh@niaid.nih.gov NR 23 TC 17 Z9 17 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3500 EP 3501 DI 10.1073/pnas.0600551103 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300003 PM 16505349 ER PT J AU Fugmann, SD Messier, C Novack, LA Cameron, RA Rast, JP AF Fugmann, SD Messier, C Novack, LA Cameron, RA Rast, JP TI An ancient evolutionary origin of the Rag1/2 gene locus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adaptive immune system; evolution; recombination activating gene ID ANTIGEN RECEPTOR GENES; V(D)J RECOMBINATION; IMMUNE-SYSTEM; ACTIVE-SITE; RAG2; IDENTIFICATION; RESIDUES; SEQUENCE; REVEALS; PHYLOGENY AB The diversity of antigen receptors in the adaptive immune system of jawed vertebrates is generated by a unique process of somatic gene rearrangement known as V(D)J recombination. The Rag1 and Rag2 proteins are the key mediators of this process. They are encoded by a compact gene cluster that has exclusively been identified in animal species displaying V(D)J-mediated immunity, and no homologous gene pair has been identified in other organisms. This distinctly restricted phylogenetic distribution has led to the hypothesis that one or both of the Rag genes were coopted after horizontal gene transfer and assembled into a Rag1/2 gene cluster in a common jawed vertebrate ancestor. Here, we identify and characterize a closely linked pair of genes, SpRag1L and SpRag2L, from an invertebrate, the purple sea urchin (Strongylocentrotus purpuratus) with similarity in both sequence and genomic organization to the vertebrate Rag1 and Rag2 genes. They are coexpressed during development and in adult tissues, and recombinant versions of the proteins form a stable complex with each other as well as with Rag1 and Rag2 proteins from several vertebrate species. We thus conclude that SpRag1L and SpRag2L represent homologs of vertebrate Rag1 and Rag2. In combination with the apparent absence of V(D)J recombination in echinoderms, this finding strongly suggests that linked Rag1- and Rag2-like genes were already present and functioning in a different capacity in the common ancestor of living deuterostomes, and that their specific role in the adaptive immune system was acquired much later in an early jawed vertebrate. C1 NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. Univ Toronto, Sunnybrook & Womens Res Inst, Toronto, ON M4N 3M5, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M4N 3M5, Canada. CALTECH, Div Biol, Pasadena, CA 91125 USA. RP Rast, JP (reprint author), NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM jrast@swri.ca OI Cameron, R. Andrew/0000-0003-3947-6041 FU Intramural NIH HHS NR 34 TC 91 Z9 94 U1 3 U2 11 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 MAR 7 PY 2006 VL 103 IS 10 BP 3728 EP 3733 DI 10.1073/pnas.0509720103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300042 PM 16505374 ER PT J AU Cicala, C Arthos, J Martinelli, E Censoplano, N Cruz, CC Chung, E Selig, SM Van Ryk, D Yang, J Jagannatha, S Chun, TW Ren, P Lempicki, RA Fauci, AS AF Cicala, C Arthos, J Martinelli, E Censoplano, N Cruz, CC Chung, E Selig, SM Van Ryk, D Yang, J Jagannatha, S Chun, TW Ren, P Lempicki, RA Fauci, AS TI R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycoprotein 120; microarray; tropism; viral replication; signal transduction ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; MEK/ERK SIGNALING PATHWAY; MACROPHAGE-TROPIC HIV; CHEMOKINE RECEPTOR; CORECEPTOR USAGE; NUCLEAR FACTOR; INFECTION; ACTIVATION; KINASE AB HIV envelope binds to and signals through its primary cellular receptor, CD4, and through a coreceptor, either CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). Here, we evaluate the response of peripheral blood mononuclear cells to a panel of genetically diverse R5 and X4 envelope proteins. Modulation of gene expression was evaluated by using oligonucleotide microarrays. Activation of transcription factors was evaluated by using an array of oligonucleotides encoding transcription factor binding sites. Responses were strongly influenced by coreceptor specificity. Treatment of cells from CCR5 Delta 32 homozygous donors with glycoprotein (gp)120 derived from an R5 virus demonstrated that the majority of responses elicited by R5 envelopes required engagement of CCR5. IRS envelopes, to a greater extent than X4 envelopes, induced the expression of genes belonging to mitogen-activated protein kinase signal transduction pathways and genes regulating the cell cycle. A number of genes induced by R5, but not X4, envelopes were also up-regulated in the resting CD4(+) T cell population of HIV-infected individuals. These results suggest that R5 envelope facilitates replication of HIV in the pool of resting CD4+ T cells. Additionally, signaling by R5 gp120 may facilitate the transmission of R5 viruses by inducing a permissive environment for HIV replication. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. RP Cicala, C (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM ccicala@niaid.nih.gov; afauci@niaid.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 39 TC 44 Z9 46 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3746 EP 3751 DI 10.1073/pnas.0511237103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300045 PM 16505369 ER PT J AU Kriegeskorte, N Goebel, R Bandettini, P AF Kriegeskorte, N Goebel, R Bandettini, P TI Information-based functional brain mapping SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuroimaging; functional magnetic resonance imaging; statistical analysis ID FALSE DISCOVERY RATE; VISUAL-CORTEX; REPRESENTATION; OBJECTS; FMRI; SEGMENTATION; PATTERNS AB The development of high-resolution neuroimaging and multielectrode electrophysiological recording provides neuroscientists with huge amounts of multivariate data. The complexity of the data creates a need for statistical summary, but the local averaging standardly applied to this end may obscure the effects of greatest neuroscientific interest. In neuroimaging, for example, brain mapping analysis has focused on the discovery of activation, i.e., of extended brain regions whose average activity changes across experimental conditions. Here we propose to ask a more general question of the data: Where in the brain does the activity pattern contain information about the experimental condition? To address this question, we propose scanning the imaged volume with a "searchlight," whose contents are analyzed multivariately at each location in the brain. C1 NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Maastricht, Fac Psychol, Dept Cognit Neurosci, NL-6229 ER Maastricht, Netherlands. RP Kriegeskorte, N (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bldg 10,Room 1D80B,10 Ctr Dr MSC 1148, Bethesda, MD 20892 USA. EM niko@nih.gov RI Bandettini, Peter/F-5871-2012; OI Kriegeskorte, Nikolaus/0000-0001-7433-9005 NR 25 TC 735 Z9 742 U1 6 U2 62 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 MAR 7 PY 2006 VL 103 IS 10 BP 3863 EP 3868 DI 10.1073/pnas.0600244103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300065 PM 16537458 ER PT J AU Sieving, PA Caruso, RC Tao, W Coleman, HR Thompson, DJS Fullmer, KR Bush, RA AF Sieving, PA Caruso, RC Tao, W Coleman, HR Thompson, DJS Fullmer, KR Bush, RA TI Ciliary neurotrophic factor (CNTF) for human retinal degeneration: Phase I trial of CNTF delivered by encapsulated cell intraocular implants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE clinical trial; neurodegeneration; retinitis pigmentosa; photoreceptor; macular degeneration ID AMYOTROPHIC-LATERAL-SCLEROSIS; ACID RAT MODEL; RETINITIS-PIGMENTOSA; HUNTINGTONS-DISEASE; PHOTORECEPTOR DEGENERATION; FACTOR-RECEPTOR; ANIMAL-MODELS; GENE-TRANSFER; FACTOR RHCNTF; SURVIVAL AB Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human CNTF gene and sequestered within capsules that were surgically implanted into the vitreous of the eye. The outer membrane of the encapsulated cell implant is semipermeable to allow CNTF to reach the retina. Ten participants received CNTF implants in one eye. When the implants were removed after 6 months, they contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be therapeutic for retinal degeneration in rcd1 dogs. Although the trial was not powered to form a judgment as to clinical efficacy, of seven eyes for which visual acuity could be tracked by conventional reading charts, three eyes reached and maintained improved acuities of 10-15 letters, equivalent to two- to three-line improvement on standard Snellen acuity charts. A surgically related choroidal detachment in one eye resulted in a transient acuity decrease that resolved with conservative management. This Phase I trial indicated that CNTF is safe for the human retina even with severely compromised photoreceptors. The approach to delivering therapeutic proteins to degenerating retinas using encapsulated cell implants may have application beyond disease caused by genetic mutations. C1 NIH, NEI, Bethesda, MD 20892 USA. NIH, Natl Inst Deafness & Other Commun Disorders, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD 20850 USA. Neurotech USA, Lincoln, RI 02865 USA. RP Sieving, PA (reprint author), NIH, NEI, Bldg 31,Room 6A03,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS; NEI NIH HHS [N01-EY-1-2113] NR 50 TC 331 Z9 346 U1 2 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3896 EP 3901 DI 10.1073/pnas.0600236103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300071 PM 16505355 ER PT J AU Jacobs, S Lie, DC DeCicco, KL Shi, Y DeLuca, LM Gage, FH Evans, RM AF Jacobs, S Lie, DC DeCicco, KL Shi, Y DeLuca, LM Gage, FH Evans, RM TI Retinoic acid is required early during adult neurogenesis in the dentate gyrus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hippocampus; neural stem cells; retinoic acid receptor; vitamin A ID CENTRAL-NERVOUS-SYSTEM; VITAMIN-A-DEFICIENCY; NEURAL STEM-CELLS; MOUSE-BRAIN; HIPPOCAMPAL NEUROGENESIS; INT-1 PROTOONCOGENE; RECEPTOR; NEURONS; INDUCTION; DIFFERENTIATION AB Retinoic acid (RA) is commonly used in vitro to differentiate stem cell populations including adult neural stem cells into neurons; however, the in vivo function of RA during adult neurogenesis remains largely unexplored. We found that depletion of RA in adult mice leads to significantly decreased neuronal differentiation within the granular cell layer of the dentate gyrus. RA contribution to neurogenesis occurs early, for RA deficiency also results in a decrease in newborn cells expressing an immature neuronal marker. Furthermore, although proliferation is unaffected during RA absence, cell survival is significantly reduced. Finally, a screen for retinoid-induced genes identifies metabolic targets including the lipid transporters, CD-36 and ABCA-1, the lipogenic master regulator SREIBP1c as well as components of the Writ signaling pathway. Our results reveal RA as a crucial contributor to early stages of adult neurogenesis and survival in vivo. C1 Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. RP Evans, RM (reprint author), Salk Inst Biol Studies, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM evans@salk.edu FU NICHD NIH HHS [HD27183, R01 HD027183] NR 50 TC 141 Z9 152 U1 4 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3902 EP 3907 DI 10.1073/pnas.0511294103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300072 PM 16505366 ER PT J AU Erxleben, C Liao, YH Gentile, S Chin, D Gomez-Alegria, C Mori, Y Birnbaumer, L Armstrong, DL AF Erxleben, C Liao, YH Gentile, S Chin, D Gomez-Alegria, C Mori, Y Birnbaumer, L Armstrong, DL TI Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium/calmodulin-dependent protein kinase type II; calcineurin; dihydropyridine; excitotoxicity ID PROTEIN-KINASE-II; CA2+ CHANNELS; CALMODULIN KINASE; VENTRICULAR MYOCYTES; SYNAPTIC PLASTICITY; DIHYDROPYRIDINE; MECHANISMS; PHOSPHATASES; FACILITATION; CALCINEURIN AB Calcium channels in the plasma membrane rarely remain open for much more than a millisecond at any one time, which avoids raising intracellular calcium to toxic levels. However, the dihydropyridine-sensitive calcium channels of the CaV1 family, which selectively couple electrical excitation to endocrine secretion, cardiovascular contractility, and neuronal transcription, have a unique second mode of gating, "mode 2," that involves frequent openings of much longer duration. Here we report that two human conditions, cyclosporin neurotoxicity and Timothy syndrome, increase mode 2 gating of the recombinant rabbit CaV1.2 channel. In each case mode 2 gating depends on a Ser residue at the cytoplasmic end of the S6 helix in domain I (Ser-439, Timothy syndrome) or domain IV (Ser-1517, cyclosporin). Both Ser reside in consensus sequences for type II calmodulin-dependent protein kinase. Pharmacologically inhibiting type II calmodulin-dependent protein kinase or mutating the Ser residues to Ala prevents the increase in mode 2 gating. We propose that aberrant phosphorylation, or "phosphorylopathy," of the CaV1.2 channel protein contributes to the excitotoxicity associated with Timothy syndrome and with chronic cyclosporin treatment of transplant patients. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Physiol Sci, Okazaki, Aichi 4448585, Japan. RP Birnbaumer, L (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov; armstro3@niehs.nih.gov FU Intramural NIH HHS NR 30 TC 70 Z9 72 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 7 PY 2006 VL 103 IS 10 BP 3932 EP 3937 DI 10.1073/pnas.0511322103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300077 PM 16537462 ER PT J AU Nepomnaschy, PA Welch, KB McConnell, DS Low, BS Strassmann, BI England, BG AF Nepomnaschy, PA Welch, KB McConnell, DS Low, BS Strassmann, BI England, BG TI Cortisol levels and very early pregnancy loss in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE stress; miscarriage; placentation; fetomaternal conflict; evolutionary theory ID CORTICOTROPIN-RELEASING HORMONE; LABORATORY PSYCHOSOCIAL STRESS; SPONTANEOUS-ABORTION; RECURRENT MISCARRIAGE; NATURAL SELECTION; CUSHINGS-SYNDROME; RESPONSES; WOMEN; AXIS; IMPLANTATION AB Maternal stress is commonly cited as an important risk factor for spontaneous abortion. For humans, however, there is little physiological evidence linking miscarriage to stress. This lack of evidence may be attributable to a paucity of research on maternal stress during the earliest gestational stages. Most human studies have focused on "clinical" pregnancy (>6 weeks after the last menstrual period). The majority of miscarriages, however, occur earlier, within the first 3 weeks after conception (approximate to 5 weeks after the last menstrual period). Studies focused on clinical pregnancy thus miss the most critical period for pregnancy continuance. We examined the association between miscarriage and levels of maternal urinary cortisol during the first 3 weeks after conception. Pregnancies characterized by increased maternal cortisol during this period (within participant analyses) were more likely to result in spontaneous abortion (P < 0.05). This evidence links increased levels in this stress marker with a higher risk of early pregnancy loss in humans. C1 Univ Michigan, Dept Anthropol, Ann Arbor, MI 48109 USA. Univ Michigan, Womens Hosp L4000, Dept Obstet & Gynecol, Reprod Sci Program, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Nat Resources & Environm, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Social Res, Res Ctr Grp Dynam, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Nepomnaschy, PA (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, POB 12233,MD A3-05,Room 309,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nepomnaschyp@niehs.nih.gov NR 71 TC 107 Z9 110 U1 1 U2 11 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 MAR 7 PY 2006 VL 103 IS 10 BP 3938 EP 3942 DI 10.1073/pnas.0511183103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 024VU UT WOS:000236225300078 PM 16495411 ER PT J AU Zhang, WY Matrisian, LM Holmbeck, K Vick, CC Rosenthal, EL AF Zhang, WY Matrisian, LM Holmbeck, K Vick, CC Rosenthal, EL TI Fibroblast-derived MT1-MMP promotes tumor progression in vitro and in vivo SO BMC CANCER LA English DT Article ID SQUAMOUS-CELL CARCINOMA; MATRIX METALLOPROTEASE INDUCER; EXTRACELLULAR-MATRIX; DEFICIENT MICE; GELATINASE-A; ORAL-CAVITY; GROWTH; HEAD; EXPRESSION; INVASION AB Background: Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases ( MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas ( HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. Methods: The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. Results: Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels. WT fibroblasts stimulated FaDu tumor cell invasion in coculture. This invasive phenotype was unaffected by combination with MMP-9 null fibroblasts, reduced with MMP-2 null fibroblasts (50%) and abrogated in MT1-MMP null fibroblasts. Co-injection of FaDu tumor cells with fibroblasts in an orthotopic oral cavity SCID mouse model demonstrated a reduction of tumor volume using MMP-9 and MMP-2 null fibroblasts (48% and 49%, respectively) compared to WT fibroblasts. Consistent with in vitro studies, MT1-MMP null fibroblasts when co-injected with FaDu cells resulted in a 90% reduction in tumor volume compared to FaDu cells injected with WT fibroblasts. Conclusion: These data suggest a role for fibroblast-derived MMP-2 and MT1-MMP in HNSCC tumor invasion in vitro and tumor growth in vivo. C1 Univ Alabama, Dept Surg, Div Otolaryngol Head & Neck Surg, Birmingham, AL 35294 USA. Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Alabama, Dept Surg, Div Gastrointestinal Surg, Birmingham, AL 35294 USA. RP Rosenthal, EL (reprint author), Univ Alabama, Dept Surg, Div Otolaryngol Head & Neck Surg, Birmingham, AL 35294 USA. EM Wenyue.Zhang@ccc.uab.edu; Lynn.Matrisian@Vanderbilt.edu; kholmbeck@dir.nidcr.nih.gov; cvick@uab.edu; oto@uab.edu RI Debatin, Klaus-Michael/J-9704-2014 OI Debatin, Klaus-Michael/0000-0002-8397-1886 FU NIDCR NIH HHS [R03 DE016049, DE16049] NR 29 TC 54 Z9 54 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 6 PY 2006 VL 6 AR 52 DI 10.1186/1471-2407-6-52 PG 9 WC Oncology SC Oncology GA 037IP UT WOS:000237140600001 PM 16515711 ER PT J AU Adamik, B Islam, A Hawari, F Rouhani, F Yu, ZX Combs, C Zhang, J Levine, SJ AF Adamik, B Islam, A Hawari, F Rouhani, F Yu, ZX Combs, C Zhang, J Levine, SJ TI Identification of RBMX as an ARTS-1-associated protein that mediates soluble TNFR1 release SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A61 EP A61 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500295 ER PT J AU Alkhalil, A Cohn, JV Wagner, MA Cabrera, JS Rajapandi, T Desai, SA AF Alkhalil, A Cohn, JV Wagner, MA Cabrera, JS Rajapandi, T Desai, SA TI The principle anion channel on P-falciparum-infected human erythrocytes is likely parasite-encoded SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAID, LMVR, NIH, Rockville, MD 20852 USA. RI Desai, Sanjay/B-7110-2009 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A463 EP A463 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503533 ER PT J AU Andrews, KW Schweitzer, A Zhao, C Holden, J Roseland, J Brandt, M Spease, C Woo, J Dwyer, J Picciano, M Saldanha, LG Fisher, K Betz, JM Yetley, E AF Andrews, KW Schweitzer, A Zhao, C Holden, J Roseland, J Brandt, M Spease, C Woo, J Dwyer, J Picciano, M Saldanha, LG Fisher, K Betz, JM Yetley, E TI Caffeine, theobromine and theophylline content of commonly purchased weight loss and sports performance enhancing dietary supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 USDA, Nutrient Data Lab, Beltsville, MD 20705 USA. FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A180 EP A180 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501291 ER PT J AU Antalis, TM Netzel-Arnett, S Hess, RA Bugge, TH AF Antalis, TM Netzel-Arnett, S Hess, RA Bugge, TH TI The membrane anchored serine protease Testisin in sperm biology SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A49 EP A50 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500238 ER PT J AU Bansal, G Xie, ZH Gant, V Druey, K AF Bansal, G Xie, ZH Gant, V Druey, K TI Regulation of mast cell responses by Rgs13 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A255 EP A255 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502123 ER PT J AU Bartali, B Frongillo, EA Lauretani, F Bandinelli, S Semba, RD Guralnik, JM Ferrucci, L AF Bartali, B Frongillo, EA Lauretani, F Bandinelli, S Semba, RD Guralnik, JM Ferrucci, L TI Effect of protein intake on change in muscle strength in older persons: does inflammation matter? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Cornell Univ, Ithaca, NY 14853 USA. Tuscany Reg Agcy Hlth, I-50100 Florence, Italy. ASF, Geriatr Rehabil Unit, I-50100 Florence, Italy. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIA, Epidemiol & Demog Sect, NIH, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21225 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A158 EP A159 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501197 ER PT J AU Bazinet, RP Rapoport, SI Weis, MT AF Bazinet, RP Rapoport, SI Weis, MT TI High throughput screen for anti-manic drug candidates SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX 79106 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A689 EP A689 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505464 ER PT J AU Bazinet, RP Rao, JS Ertley, RN Rapoport, SI Lee, HJ AF Bazinet, RP Rao, JS Ertley, RN Rapoport, SI Lee, HJ TI Chronic fluoxetine increases the activity of brain cytosolic phospholipase A(2) and the incorporation rate of arachidonic acid into brain phospholipid of the unanesthetized rat SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RI Rao, Jagadeesh/C-1250-2009 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A487 EP A487 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504103 ER PT J AU Bell, JK Askins, J Hall, PR Davies, DR Segal, DM AF Bell, JK Askins, J Hall, PR Davies, DR Segal, DM TI The dsRNA binding site of human toll-like receptor 3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDDK, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RI Bell, Jessica/I-3893-2013 OI Bell, Jessica/0000-0003-1455-3274 NR 0 TC 1 Z9 1 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 MAR 6 PY 2006 VL 20 IS 4 BP A96 EP A96 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500459 ER PT J AU Brister, JR Nossal, NG AF Brister, JR Nossal, NG TI Bacteriophage T4 DNA synthesis is initiated from several origins of replication SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A511 EP A511 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504215 ER PT J AU Carlson, BA Jeong, SJ Shrimali, RK Hatfield, D AF Carlson, BA Jeong, SJ Shrimali, RK Hatfield, D TI The selenocysteine tRNA Staf region is essential for adequate selenoprotein levels and mouse longevity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, LCP, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A428 EP A428 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503364 ER PT J AU Castrop, H Oppermann, M Weiss, Y Huang, YN Mizel, D Theilig, F Bachmann, S Briggs, J Kurtz, A Schnermann, J AF Castrop, H Oppermann, M Weiss, Y Huang, YN Mizel, D Theilig, F Bachmann, S Briggs, J Kurtz, A Schnermann, J TI Transgenic mice expressing Cre recombinase under the control of the human renin promoter SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany. NIDDK, NIH, Bethesda, MD 20892 USA. Charite Univ Med, Inst Anat, D-10115 Berlin, Germany. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A344 EP A344 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502526 ER PT J AU Chen, YP Goldstein, JA AF Chen, YP Goldstein, JA TI PGC-1 alpha regulates both the constitutive and drug-inducible expression of human CYP2C9 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, LPC, NIH, Res Triangle Pk, NC 27709 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A260 EP A260 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502145 ER PT J AU Collins, CB Winham, DM Hutchins, AM Salbe, AD AF Collins, CB Winham, DM Hutchins, AM Salbe, AD TI Dietary intake, characteristics, and attitudes of self-reported low-carbohydrate dieters SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Arizona State Univ, Mesa, AZ 85212 USA. NIH, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A575 EP A575 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504518 ER PT J AU Cope, KA Milner, JA Seifried, R Seifried, HE Harrison, EH AF Cope, KA Milner, JA Seifried, R Seifried, HE Harrison, EH TI Effects of garlic ingestion in humans on the formation of urinary nitrosoproline SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 USDA ARS, BHNRC, Phytonutrients Lab, Beltsville, MD 20705 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A152 EP A152 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501168 ER PT J AU Cordeiro, Y Lima, LM Marques, A Oliveira, C Tinoco, L Sampath, S Foguel, D Torriani, I Caughey, B Silva, J AF Cordeiro, Y Lima, LM Marques, A Oliveira, C Tinoco, L Sampath, S Foguel, D Torriani, I Caughey, B Silva, J TI Structural basis for nucleic acid binding to the prion protein SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Inst Med Biochem, BR-21941590 Rio De Janeiro, Brazil. Sch Pharm, BR-21941590 Rio De Janeiro, Brazil. Univ Estadual Campinas, Phys Inst Gleb Wataghin, BR-13083970 Campinas, SP, Brazil. CCS BH1, BR-21941590 Rio De Janeiro, Brazil. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RI Torriani, Iris/E-5686-2010; Cordeiro, Yraima/J-7619-2012; Tinoco, Luzineide/G-3630-2014; Inst. of Physics, Gleb Wataghin/A-9780-2017 OI Cordeiro, Yraima/0000-0003-4278-212X; Tinoco, Luzineide/0000-0002-1299-6242; NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A95 EP A95 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500452 ER PT J AU DiLullo, C Mattioli, PM Johnson, C Foust, A AF DiLullo, C Mattioli, PM Johnson, C Foust, A TI Comparison of laminin reorganization in primary skeletal muscle cultures grown on collagen I and synthetic matrices SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Philadelphia Coll Osteopath Med, Philadelphia, PA 19131 USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A29 EP A30 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500139 ER PT J AU Do Carmo, GP Mello, NK Rice, KC Negus, SS AF Do Carmo, GP Mello, NK Rice, KC Negus, SS TI Effects of the selective delta opioid agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A238 EP A239 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502047 ER PT J AU Eiden, LE Vaudry, D Ravni, A Gerdin, M AF Eiden, LE Vaudry, D Ravni, A Gerdin, M TI Canonical and noncanonical cAMP-dependent signaling pathways activated by PACAP in neuroendocrine cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIMH, Mol Neurobiol Sect, iRP, Bethesda, MD 20892 USA. Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol, F-76821 Rouen, France. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A694 EP A694 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505489 ER PT J AU Fan, L Santoro, D Palicz, A Li, L Lewis, EM Ledford, BG Leto, TL Sergeant, S McPhail, LC AF Fan, L Santoro, D Palicz, A Li, L Lewis, EM Ledford, BG Leto, TL Sergeant, S McPhail, LC TI Activation of protein kinase C via phospholipase D enhances NADPH oxidase activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA. RI McPhail, Linda/D-9505-2013 OI McPhail, Linda/0000-0002-8670-306X NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A484 EP A484 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504089 ER PT J AU Fedorova, IM Nguyen, V Salem, N AF Fedorova, IM Nguyen, V Salem, N TI N-3 fatty acid deficient diet affects rat spatial performance in the Barnes circular maze. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A138 EP A138 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501105 ER PT J AU Franco, R Cidlowski, JA AF Franco, R Cidlowski, JA TI Glutathione efflux through an SLCO/OATP-like transporter is necessary for the progression of FasL-induced apoptosis in Jurkat cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A121 EP A121 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501031 ER PT J AU Free, RB Hazelwood, LA Spalding, HN Cabrera, DM Sibley, DR AF Free, RB Hazelwood, LA Spalding, HN Cabrera, DM Sibley, DR TI The chaperone protein calnexin regulates cell surface expression of both D-1 and D-2 dopamine receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Cabrera, David/I-1013-2014 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A247 EP A247 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502084 ER PT J AU Furimsky, AM Sharp, LEH Bettridge, A Kapetanovic, IM Green, CE Iyer, LV AF Furimsky, AM Sharp, LEH Bettridge, A Kapetanovic, IM Green, CE Iyer, LV TI Inhibition of human hepatic and jejunal estradiol sulfation by resveratrol and piceatannol SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 SRI Int, Menlo Pk, CA 94025 USA. 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PD MAR 6 PY 2006 VL 20 IS 4 BP A264 EP A265 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502167 ER PT J AU Gasior, M French, A Joy, M Yankura, J Hartman, A Rogawski, MA AF Gasior, M French, A Joy, M Yankura, J Hartman, A Rogawski, MA TI Anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal or pyruvic acid SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NINS, NIH, Epilepsy Res Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A688 EP A689 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505463 ER PT J AU Graves, JP Wang, H Bradbury, JA Zeldin, DC AF Graves, JP Wang, H Bradbury, JA Zeldin, DC TI Cloning and characterization of three new mouse P450 enzymes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A458 EP A458 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503508 ER PT J AU Hampton, D Druey, K AF Hampton, D Druey, K TI The role of RGS16 in T lymphocyte responses SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAID, Mol Signal Transduct Sect, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 1 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 MAR 6 PY 2006 VL 20 IS 4 BP A255 EP A255 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502122 ER PT J AU Hazelwood, LA Free, RB Cabrera, DM Spalding, HN Neiman, J Sibley, DR AF Hazelwood, LA Free, RB Cabrera, DM Spalding, HN Neiman, J Sibley, DR TI Characterization of D-1 and D-2 dopamine receptor interactions with the Na+/K+-ATPase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NINDS, NIH, Bethesda, MD 20892 USA. RI Cabrera, David/I-1013-2014 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A247 EP A247 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502085 ER PT J AU Heilig, M AF Heilig, M TI Neuropeptide Y in anxiety and alcoholism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A416 EP A416 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503307 ER PT J AU Holden, J Roseland, J Andrews, K Zhao, C Schweitzer, A Perry, C Harnly, J Wolf, W Dwyer, J Picciano, MF Betz, J Saidanha, L Yetley, E Fisher, K Sharpless, K Radimer, K Wilgert, J AF Holden, J Roseland, J Andrews, K Zhao, C Schweitzer, A Perry, C Harnly, J Wolf, W Dwyer, J Picciano, MF Betz, J Saidanha, L Yetley, E Fisher, K Sharpless, K Radimer, K Wilgert, J TI Dietary supplement ingredient database (DSID) project: Pilot study update SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 USDA, Beltsville, MD 20705 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A564 EP A564 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504464 ER PT J AU Hosseinpour, F Moore, R Negishi, M Sueyoshi, T AF Hosseinpour, F Moore, R Negishi, M Sueyoshi, T TI Serine-202 regulates the nuclear translocation of constitutive active/androstane receptor CAR SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A261 EP A261 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502152 ER PT J AU Houston, D Nicklas, B Tamara, HS Frances, TY Newman, A Lee, JS Sahyoun, N Sellmeyer, D Visser, M Kritchevsky, S AF Houston, D Nicklas, B Tamara, HS Frances, TY Newman, A Lee, JS Sahyoun, N Sellmeyer, D Visser, M Kritchevsky, S TI Dietary protein and change in appendicular lean mass in older adults: The health ABC study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Wake Forest Univ, Winston Salem, NC 27157 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vrije Univ Amsterdam, Amsterdam, Netherlands. RI Sahyoun, Nadine/G-2608-2011; Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A555 EP A555 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504423 ER PT J AU Ilnytska, O Mashtalir, N Drel, VR Pacher, P Yorek, MA Obrosova, IG AF Ilnytska, O Mashtalir, N Drel, VR Pacher, P Yorek, MA Obrosova, IG TI Poly(ADP-ribose)polymerase-1 (PARP) activation and diabetic neuropathic pain SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. NIAAA, NIH, Rockville, MD 20852 USA. Univ Iowa, Vet Affairs Med Ctr, Iowa City, IA 52246 USA. RI Drel, Viktor/G-8883-2016 OI Drel, Viktor/0000-0003-4542-0132 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A777 EP A778 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206506328 ER PT J AU Irons, R Carlson, BA Hatfield, DL Davis, CD AF Irons, R Carlson, BA Hatfield, DL Davis, CD TI Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, LCP, NIH, Bethesda, MD 20892 USA. NCI, Nutr Sci Res Grp, NIH, Rockville, MD 20852 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A428 EP A429 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503367 ER PT J AU Islam, A Levine, SJ AF Islam, A Levine, SJ TI NUCB2, an ARTS-1 interacting and calcium-binding protein, that promotes the extracellular release of TNFR1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, PCCMB, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A61 EP A61 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500293 ER PT J AU Jackson, JP Ferguson, SS Negishi, M Goldstein, JA AF Jackson, JP Ferguson, SS Negishi, M Goldstein, JA TI The, constitutive androstane receptor mediates phenytoin induction of cyp2c37 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27606 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A260 EP A260 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502146 ER PT J AU Jayasinghe, LN Miles, G Bayley, H AF Jayasinghe, LN Miles, G Bayley, H TI Role of the amino latch of staphylococcal alpha-hemolysin and leukocidin in pore formation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A518 EP A518 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504249 ER PT J AU Jeong, J Levine, RL AF Jeong, J Levine, RL TI Desferrioxamine is both an iron chelator and a lysosomotropic amine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, LB, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A49 EP A49 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500235 ER PT J AU Johnson, DT Harris, RA Balaban, RA AF Johnson, DT Harris, RA Balaban, RA TI Proteomic comparison of heart and liver mitochondria in diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Biohem & Mol Biol, Indianapolis, IN 46202 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A65 EP A66 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500314 ER PT J AU Jozwiak, K Moaddel, R Yamaguchi, R Maciuk, A Wainer, IW AF Jozwiak, K Moaddel, R Yamaguchi, R Maciuk, A Wainer, IW TI The non-competitive inhibitory activities of morphinan and morphine-derivatives at the alpha 3 beta 4 neuronal acetylcholine receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Med Univ Lublin, Lublin, Poland. NIA, GRC, NIH, Baltimore, MD 20874 USA. NIA, GRC, NIH, Baltimore, MD 21224 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A245 EP A245 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502075 ER PT J AU Kim, BJ Song, BJ AF Kim, BJ Song, BJ TI JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation, mitochondrial translocation and apoptosis: a novel mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIA, Lab Membrane Biochem & Biophys, NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A120 EP A120 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501027 ER PT J AU Kim, JS Anthony, KH Moller, M Gaildrat, P Klein, DC AF Kim, JS Anthony, KH Moller, M Gaildrat, P Klein, DC TI Down-regulation of the pineal response to adrenergic stimulation mediated by cAMP induction of phosphodiesterase 4B2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIH, LDN, Bethesda, MD 20892 USA. Univ Alberta, Edmonton, AB T6G 2H7, Canada. Univ Copenhagen, DK-2200 Copenhagen, Denmark. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A543 EP A543 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504367 ER PT J AU Kim, SJ Zhang, ZJ Hitomi, E Mukherjee, AB AF Kim, SJ Zhang, ZJ Hitomi, E Mukherjee, AB TI Endoplasmic reticulum stress-mediated caspase-4 activation and apoptosis lead to neurodegeneration in INCL SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A506 EP A507 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504195 ER PT J AU Kim, YS Kang, HS Herbert, R Jetten, AM AF Kim, YS Kang, HS Herbert, R Jetten, AM TI The Novel Glis2 protein has critical roles in kidney development and renal failure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, LRB CB, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, LEP PS, NIH, Res Triangle Pk, NC 27709 USA. 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NIDA, Intramural Res Program, Psychobiol Sect, Baltimore, MD 21224 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A678 EP A678 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505415 ER PT J AU Kunkel, TA AF Kunkel, TA TI Structure-function studies of DNA replication fidelity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Mol Genet Lab, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, DHHS, Res Triangle Pk, NC 27709 USA. 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Benaroya Res Inst, Hope Heart Program, Seattle, WA 98101 USA. RI Roberts, David/A-9699-2008; Day, Anthony/O-1658-2015 OI Roberts, David/0000-0002-2481-2981; Day, Anthony/0000-0002-1415-3134 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. 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RI Gladyshev, Vadim/A-9894-2013 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A428 EP A428 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503365 ER PT J AU Lee, DY Gruschus, JM AF Lee, DY Gruschus, JM TI NMR solution structure of human sulfiredoxin (hSrx) and structural basis for the reduction of cysteine-sulfinic acid SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A508 EP A508 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504204 ER PT J AU Lee, SJ Coulter, S Jetten, AM Goldstein, JA AF Lee, SJ Coulter, S Jetten, AM Goldstein, JA TI Identification and functional studies of human CYP26A1 Single Nucleotide Polymorphisms (SNPs) in racially diverse populations SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A264 EP A264 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502165 ER PT J AU Li, SM Katz, JL AF Li, SM Katz, JL TI Clonidine potentiation of morphine discriminative stimulus-modulated by alpha2 noradrenergic receptor mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDA, Medicat Discovery Res Branch, NIH, DHHS, Baltimore, MD 21224 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A680 EP A680 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505425 ER PT J AU Lo, CWY Shen, Y Yu, Q Leatherbury, L AF Lo, CWY Shen, Y Yu, Q Leatherbury, L TI In vivo imaging of mouse cardiovascular development and disease by high frequency ultrasound SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, NIH, Lab Dev Biol, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A4 EP A4 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500019 ER PT J AU Lu, QS Asico, LD Jones, JE Wang, Z Villar, VAM Bai, RK Schnackenberg, CG Sibley, DR Jose, PA AF Lu, QS Asico, LD Jones, JE Wang, Z Villar, VAM Bai, RK Schnackenberg, CG Sibley, DR Jose, PA TI D5 dopamine receptor regulation of Cu/Zn SOD expression and activity in D5 receptor deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Georgetown Univ, Ctr Med, Washington, DC 20057 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. GlaxoSmithKline Pharmaceut, Dept Renal Biol, King Of Prussia, PA 19406 USA. NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A309 EP A309 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502373 ER PT J AU Makino, A Prossnitz, ER Bunemann, M Wang, JM Yao, WJ Schmid-Schonbein, GW AF Makino, A Prossnitz, ER Bunemann, M Wang, JM Yao, WJ Schmid-Schonbein, GW TI G protein-coupled receptor as a mechanosensor for fluid shear in neutrophil SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NCI, Canc Res Ctr, Ft Detrick, MD 21702 USA. Univ Wurzburg, Wurzburg, Germany. RI Prossnitz, Eric/B-4543-2008 NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A281 EP A281 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502245 ER PT J AU Miller, DS Hartz, AMS Bauer, B AF Miller, DS Hartz, AMS Bauer, B TI Time-dependent tumor necrosis factor (TNF)-alpha signaling to P-glycoprotein (P-gp) in rat brain capillaries SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIH NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A378 EP A378 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503136 ER PT J AU Nossal, NG Jones, C Makhov, A Chastain, P Griffith, J Devos, J Mueser, T AF Nossal, NG Jones, C Makhov, A Chastain, P Griffith, J Devos, J Mueser, T TI Architecture and function of the phage T4 replication fork SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Univ Toledo, Toledo, OH 43606 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A420 EP A420 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503327 ER PT J AU Notari, L Heredia, R Balko, N Becerra, SP AF Notari, L Heredia, R Balko, N Becerra, SP TI A phospholipase A2-linked receptor for PEDF SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A115 EP A115 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501002 ER PT J AU Oka, S Kato, J Moss, J AF Oka, S Kato, J Moss, J TI Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A45 EP A45 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500217 ER PT J AU Pagel, I Mantell, B Sack, MN AF Pagel, I Mantell, B Sack, MN TI PPAR gamma agonist pioglitazone restores impaired mitochondrial biogenesis and function in insulin resistant C2C12 myotubes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 MAR 6 PY 2006 VL 20 IS 4 BP A524 EP A524 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504281 ER PT J AU Panagiotidis, M Cidlowski, JA AF Panagiotidis, M Cidlowski, JA TI Inhibition of Na+/K+-ATPase by ouabain potentiates apoptosis by inducing pertubations in cell calcium homeostasis: A protective role selective for Bcl-2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Lab Signal Transduct, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 1 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 MAR 6 PY 2006 VL 20 IS 4 BP A119 EP A119 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501022 ER PT J AU Patel, HH Head, BP Rothstein, ER Niesman, IR Roth, DM Farquhar, MG Balaban, RS Insel, PA AF Patel, HH Head, BP Rothstein, ER Niesman, IR Roth, DM Farquhar, MG Balaban, RS Insel, PA TI Localization of caveolae and mitochondria in adult cardiac myocytes: implications for reductive signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Calif San Diego, La Jolla, CA 92093 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A691 EP A691 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505473 ER PT J AU Peng, Z Beaven, MA AF Peng, Z Beaven, MA TI Regulation of the calcium signal by phospholipase (PL) D, sphingosine kinase (SK), and phosphatidylinositol 4-phosphate (PIP) 5-kinase in mast cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A117 EP A117 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501014 ER PT J AU Piszczek, G Maurizi, MR Ginsburg, A AF Piszczek, G Maurizi, MR Ginsburg, A TI Substrate binding to ClpA hexamer promotes a unique conformation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, LB, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A491 EP A491 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504120 ER PT J AU Ray, AL Ble, A Bandinelli, S Lauretani, F Bartali, B Semba, R Guralnik, JM AF Ray, AL Ble, A Bandinelli, S Lauretani, F Bartali, B Semba, R Guralnik, JM TI Association of plasma selenium with hemoglobin among older women: the InCHIANTI study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Johns Hopkins Univ, Johns Hopkins Hosp, Baltimore, MD 21287 USA. NIA, Longitudinal Studies Sect, Harbor Hosp, NIH, Baltimore, MD 21225 USA. IOT Hosp, Geriatr Rehabil Unit, I-50125 Florence, Italy. IOT Hosp, Tuscany Reg Agcy Hlth, I-50125 Florence, Italy. Cornell Univ, Div Nutr, Ithaca, NY 14853 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20815 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A141 EP A141 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501119 ER PT J AU Reichelt, M Willems, L Schnermann, J Blackburn, M Headrick, J AF Reichelt, M Willems, L Schnermann, J Blackburn, M Headrick, J TI Effects of genetic deletion of adenosine deaminase and A1 receptors in normoxic and ischemic hearts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut C1 Griffith Univ, Heart Fdn, Res Ctr, Southport, Qld 4217, Australia. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. RI Willems, Laura/B-6259-2009 NR 0 TC 0 Z9 0 U1 1 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 MAR 6 PY 2006 VL 20 IS 4 BP A743 EP A743 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206506171 ER PT J AU Reynolds, IP Davis, DA Singer, KE Haque, M Yarchoan, R AF Reynolds, IP Davis, DA Singer, KE Haque, M Yarchoan, R TI Targeted killing of Kaposi's sarcoma associated herpesvirus (KSHV)-infected lymphoma cells through hypoxia induced activation of ORF21 and ORF36 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A463 EP A464 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503535 ER PT J AU Rhee, SG Jeong, W Park, SJ Chang, TS Lee, DY AF Rhee, SG Jeong, W Park, SJ Chang, TS Lee, DY TI Molecular mechanism of the reduction of cysteine sulfinic acid of peroxiredoxin to cysteine by mammalian sulfiredoxin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A36 EP A36 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500171 ER PT J AU Romanowska, M Kikawa, KD Fields, JR Anderson, LM AF Romanowska, M Kikawa, KD Fields, JR Anderson, LM TI Selenium requirements for expression of GPxs in human lung adenocarcinoma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A146 EP A147 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501143 ER PT J AU Ruan, X Gallagher, D Harris, T Albu, J Heymsfield, S Kuznia, P Heshka, S AF Ruan, X Gallagher, D Harris, T Albu, J Heymsfield, S Kuznia, P Heshka, S TI Estimating whole-body intermuscular adipose tissue from single cross-sectional magnetic resonance images SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 St Lukes Roosevelt Hosp, Inst Human Nutr, Obes Res Ctr, New York, NY 10025 USA. NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A165 EP A165 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501225 ER PT J AU Sengupta, A Weaver, JA Novoselov, SV Fomenko, DE Carlson, BA Gladyshev, VN Hatfield, DL AF Sengupta, A Weaver, JA Novoselov, SV Fomenko, DE Carlson, BA Gladyshev, VN Hatfield, DL TI A comparative analysis of selenoproteins and global gene expression in liver selenocysteine tRNA knockout mice and its rescued variants SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A427 EP A428 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503362 ER PT J AU Shea, MK O'Donnell, CJ Hoffman, U Price, PA Dawson-Hughes, B Booth, SL AF Shea, MK O'Donnell, CJ Hoffman, U Price, PA Dawson-Hughes, B Booth, SL TI Plasma vitamin K levels are associated with coronary calcification in older adults. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Tufts Univ, HNRCA, Calcium & Bone Lab, Boston, MA 02111 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A134 EP A134 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501090 ER PT J AU Shizukuda, Y Bolan, CD Tripodi, DJ Yau, YY Smith, KP Waclawiw, MA Leitman, SF Rosing, DR AF Shizukuda, Y Bolan, CD Tripodi, DJ Yau, YY Smith, KP Waclawiw, MA Leitman, SF Rosing, DR TI Exercise performance of asymptomatic subjects with hereditary hemochromatosis: The increase in abnormal electrocardiographic changes and complex arrhythmias SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A395 EP A395 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503213 ER PT J AU Shrimali, RK Park, JM Irons, R Carlson, BA Hatfield, DL AF Shrimali, RK Park, JM Irons, R Carlson, BA Hatfield, DL TI Selenoproteins play a major role in immune function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, DCP, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A68 EP A68 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500327 ER PT J AU Stevens, LA Park, S Barbieri, J Bortell, R Moss, J AF Stevens, LA Park, S Barbieri, J Bortell, R Moss, J TI Auto-ADP-ribosylation inhibits the catalytic activity of ExoS, a type-III effector of Pseudomonas aeruginosa SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, PCCMB, NIH, Bethesda, MD 20890 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Massachusetts, Sch Med, Dept Med, Diabet Div, Worcester, MA 01605 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A45 EP A45 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500216 ER PT J AU Tabak, LA AF Tabak, LA TI All, in the family: the role of the UDP N-acetylgalactosamine polypeptide: alpha-N-acetylgalactosaminyltransferases (ppGaINAc T's) in development and disease in the craniofacial complex SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A421 EP A421 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503330 ER PT J AU Tanda, G Ebbs, AL Newman, AH Katz, JL AF Tanda, G Ebbs, AL Newman, AH Katz, JL TI Differential effects of dopamine transporter inhibitors on cocaine-stimulated dopamine neurotransmission SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIDA, Med Chem Sect, MDRB, IRP,NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Psychobiol Sect, MDRB, IRP,NIH,DHHS, Baltimore, MD 21224 USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A676 EP A676 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505406 ER PT J AU Timsit, YE Negishi, M AF Timsit, YE Negishi, M TI Nuclear translocation of CAR is dependent on ubiquitination and proteasome-mediated degradation of CAR cytoplasmic retention protein (CCRP) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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 MAR 6 PY 2006 VL 20 IS 4 BP A657 EP A658 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206505320 ER PT J AU Uthus, EO Ross, S AF Uthus, EO Ross, S TI Dietary selenium (Se) but not folic acid (FA) affects the activity and mRNA of rat liver betaine homocysteine methyltransferase (BHMT) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A429 EP A429 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503368 ER PT J AU Wang, Z Mrsny, R Wade, P Nusrat, A AF Wang, Z Mrsny, R Wade, P Nusrat, A TI Oncogenic Raf1 induces epithelial cell transformation by activating Slug and suppressing Occludin promoter activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Emory Univ, Atlanta, GA 30322 USA. Un Pharmaceut, Los Altos Hills, CA 94022 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RI Nusrat, Asma/B-3887-2009 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A201 EP A202 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206501391 ER PT J AU Williams, EA Perkins, SN Smith, NC Hursting, SD Lane, MA AF Williams, EA Perkins, SN Smith, NC Hursting, SD Lane, MA TI Carbohydrate restriction, dietary energy restriction and weight loss in obese mice: Metabolic insights SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 Univ Texas, Div Nutr Sci, Dept Human Ecol, Austin, TX 78712 USA. NCI, Frederick, MD 21702 USA. SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A582 EP A583 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206504551 ER PT J AU Xie, ZH Johnson, E Druey, KM AF Xie, ZH Johnson, E Druey, KM TI Nuclear inhibition of CREB-driven transcription by Rgs13 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NIAID, NIH, Rockville, MD 20852 USA. Merck & Co Inc, N Wales, PA 19454 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A256 EP A256 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206502128 ER PT J AU Xu, XM Carlson, BA Mix, H Irons, R Berry, MJ Gladyshev, VN Hatfield, DL AF Xu, XM Carlson, BA Mix, H Irons, R Berry, MJ Gladyshev, VN Hatfield, DL TI Selenophosphate synthetase 2 is essential for selenoprotein biosynthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, LCP, NIH, Bethesda, MD 20892 USA. NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Hawaii, Honolulu, HI 96822 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A428 EP A428 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503363 ER PT J AU Yoo, MH Xu, XM Turanov, AA Carlson, BA Gladyshev, VN Hatfield, DL AF Yoo, MH Xu, XM Turanov, AA Carlson, BA Gladyshev, VN Hatfield, DL TI siRNA knockdown-mRNA knock-in as a means of assessing selenoprotein function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NCI, LCP, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A427 EP A427 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503361 ER PT J AU Zhang, J Hawari, FI Shamburek, RD Adamik, B Kaler, M Levine, SJ AF Zhang, J Hawari, FI Shamburek, RD Adamik, B Kaler, M Levine, SJ TI Identification and characterization of TNFR1 exosome-like vesicles in human plasma SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Pharmacol & Expt Therapeut C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 MAR 6 PY 2006 VL 20 IS 4 BP A112 EP A112 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206500535 ER PT J AU Zhang, XL Donelson, E Goswami, P Song, BJ Hardwick, JP AF Zhang, XL Donelson, E Goswami, P Song, BJ Hardwick, JP TI Repression of CYP4F1 gene by peroxisome proliferators is mediated by HNF4 alpha and PPAR alpha competition for PPRE sites in the CYP4F1 promoter SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2006 Annual Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut C1 Northeastern Ohio Univ Coll Med & Pharm, LMBB, NIH, Rootstown, OH 44272 USA. NIAAA, Rockville, MD 20852 USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 6 PY 2006 VL 20 IS 4 BP A460 EP A460 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 024OW UT WOS:000236206503517 ER PT J AU Deloria-Knoll, M Steinhoff, M Semba, RD Nelson, K Vlahov, D Meinert, CL AF Deloria-Knoll, M Steinhoff, M Semba, RD Nelson, K Vlahov, D Meinert, CL TI Effect of zinc and vitamin A supplementation on antibody responses to a pneumococcal conjugate vaccine in HIV-positive injection drug users: A randomized trial SO VACCINE LA English DT Article DE vitamin A; zinc; pneumococcal vaccine; HIV ID IMMUNODEFICIENCY-VIRUS-INFECTION; TYPE-1 INFECTION; IMMUNE-RESPONSE; POLYSACCHARIDE; IMMUNIZATION; ASSAY; QUANTITATION; DEFICIENCY; MORTALITY; CHILDREN AB HIV-infected individuals have impaired immune responses to vaccines and high rates of pneumococcal disease. The effect of vitamin A and zinc supplementation on the immunogenicity of a 7-valent pneumococcal CRM-197 conjugate vaccine (PC-7) was evaluated in 118 HIV+ injection drug users. Subjects were randomized to oral 400,000 IU vitamin A, 300 mg zinc, vitamin A + zinc, or placebo, then immunized. Geometric mean titer increased 1.3-3.3-fold for all pneumococcal serotypes. PC-7 elicited an immune response in HIV-infected adults but neither vitamin A nor zinc altered the immunogenicity of the evaluated vaccines. (c) 2005 Elsevier Ltd. All rights reserved. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. NIAID, Bethesda, MD 20892 USA. RP Deloria-Knoll, M (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, 615 N Wolfe St,Room E8543, Baltimore, MD 21205 USA. EM mknoll@jhsph.edu FU NIDA NIH HHS [DA 04334] NR 36 TC 14 Z9 14 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 MAR 6 PY 2006 VL 24 IS 10 BP 1670 EP 1679 DI 10.1016/j.vaccine.2005.09.047 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 025IQ UT WOS:000236259500023 PM 16256250 ER PT J AU Jacquet, H Rapoport, JL Hecketsweiler, B Bobb, A Thibaut, F Frebourg, T Campion, D AF Jacquet, H Rapoport, JL Hecketsweiler, B Bobb, A Thibaut, F Frebourg, T Campion, D TI Hyperprolinemia is not associated with childhood onset schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE hyperprolinemia; PRODH; COS; 22q11 AB In a previous report [Jacquet et al., 2005] we have shown that mild to moderate hyperprolinemia resulting from several alterations (either a complete deletion or missense mutations) of the proline dehydrogenase (PRODH) gene located on chromosome 22q11 is a risk factor for schizoaffective disorder but not for DSM3 R schizophrenia or bipolar disorder. We now report that hyperprolinemia is not associated with childhood onset schizophrenia (COS). (C) 2006 Wiley-Liss, Inc. C1 Fac Med, INSERM, U614, F-76000 Rouen, France. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. CHU Rouen, Biochim Lab, Rouen, France. RP Campion, D (reprint author), Fac Med, INSERM, U614, F-76000 Rouen, France. EM dominique.campion@univ-rouen.fr NR 5 TC 5 Z9 5 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD MAR 5 PY 2006 VL 141B IS 2 BP 192 EP 192 DI 10.1002/ajmg.b.30263 PN B PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 009VT UT WOS:000235142200015 PM 16389584 ER PT J AU Wendler, D AF Wendler, D TI One-time general consent for research on biological samples SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID GENETIC RESEARCH; INFORMED-CONSENT; TISSUE SAMPLES; POPULATION; ATTITUDES; BLOOD; EXPERIENCE; PARTICIPATION; BIOBANKS; PROJECT C1 NIH, Dept Clin bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 32 TC 128 Z9 128 U1 1 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD MAR 4 PY 2006 VL 332 IS 7540 BP 544 EP 547 DI 10.1136/bmj.332.7540.544 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 023WB UT WOS:000236155800022 PM 16513715 ER PT J AU Bryant, J Geyer, CE AF Bryant, J Geyer, CE TI Trastuzumab for early breast cancer SO LANCET LA English DT Letter C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Bryant, J (reprint author), Natl Surg Adjuvant Breast & Bowel Project, E Commons Profess Bldg,4 Allegheny Ctr,5th Floor, Pittsburgh, PA 15212 USA. EM bryant@nsabp.pitt.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 4 PY 2006 VL 367 IS 9512 BP 728 EP 728 DI 10.1016/S0140-6736(06)68298-6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 020JX UT WOS:000235906000021 PM 16517268 ER PT J AU Lee, WK Kim, YM Malik, N Ma, C Westphal, H AF Lee, WK Kim, YM Malik, N Ma, C Westphal, H TI Cloning and characterization of the 5 '-flanking region of the Ehox gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Ehox; nuclear factor Y; 5 '-flanking ID DNA-BINDING; EXPRESSION; REPRESSOR; PROMOTER AB The paired-like homeobox-containing gene Ehox plays a role in embryonic stern cell differentiation and is highly expressed ill the developing placenta and thymus. To understand the mechanisms of regulation of Ehox gene expression, the 5'-flanking region of the Ehox gene was isolated from a mouse BAC library. 5'-RACE analysis revealed a single transcriptional start site 130 nucleotides upstream of the translation initiation codon. Transient transfection with a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the nt-84 to -68 region contained a positive cis-acting element for efficient expression of the Ehox gene. Mutational analysis of this region and oligonucleotide competition in the electrophoretic mobility shift assay revealed the presence of a CCAAT box, which is a target for transcription nuclear factor Y (NFY). NFY is essential for positive gene regulation. No tissue-specific enhancer was identified in the 1.9-kb 5'-flanking region of the Ehox gene. Ehox is expressed during the early stages of embryo development, specifically in the brain at 9.5 dpc, as well as during the late stages of embryo development. These results suggest that NFY is an essential regulatory factor for Ehox transcriptional activity, which is important for the post-implantation stage of the developing embryo. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Dept Lab Anim Med, Med Res Ctr, Coll Med, Seoul 120752, South Korea. RP Lee, WK (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM wklee@yumc.yousei.ac.kr NR 16 TC 5 Z9 5 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 MAR 3 PY 2006 VL 341 IS 1 BP 225 EP 231 DI 10.1016/j.bbrc.2005.12.176 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 012BO UT WOS:000235313400033 PM 16414020 ER PT J AU Vinogradova, TM Lyashkov, AE Zhu, WZ Ruknudin, AM Sirenko, S Yang, DM Deo, S Barlow, M Johnson, S Caffrey, JL Zhou, YY Xiao, RP Cheng, HP Stern, MD Maltsev, VA Lakatta, EG AF Vinogradova, TM Lyashkov, AE Zhu, WZ Ruknudin, AM Sirenko, S Yang, DM Deo, S Barlow, M Johnson, S Caffrey, JL Zhou, YY Xiao, RP Cheng, HP Stern, MD Maltsev, VA Lakatta, EG TI High basal protein kinase A-dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells SO CIRCULATION RESEARCH LA English DT Article DE sinoatrial node; beta-adrenergic stimulation; protein kinase A; ryanodine receptors; local Ca2+ release ID RABBIT SINOATRIAL NODE; RYANODINE RECEPTOR; NA+-CA2+ EXCHANGER; DIASTOLIC DEPOLARIZATION; INTRACELLULAR CALCIUM; ACTIVATION; RELEASE; MYOCYTES; HEART AB Local, rhythmic, subsarcolemmal Ca2+ releases (LCRs) from the sarcoplasmic reticulum (SR) during diastolic depolarization in sinoatrial nodal cells (SANC) occur even in the basal state and activate an inward Na+-Ca2+ exchanger current that affects spontaneous beating. Why SANC can generate spontaneous LCRs under basal conditions, whereas ventricular cells cannot, has not previously been explained. Here we show that a high basal cAMP level of isolated rabbit SANC and its attendant increase in protein kinase A (PKA)-dependent phosphorylation are obligatory for the occurrence of spontaneous, basal LCRs and for spontaneous beating. Gradations in basal PKA activity, indexed by gradations in phospholamban phosphorylation effected by a specific PKA inhibitory peptide were highly correlated with concomitant gradations in LCR spatiotemporal synchronization and phase, as well as beating rate. Higher levels of basal PKA inhibition abolish LCRs and spontaneous beating ceases. Stimulation of beta-adrenergic receptors extends the range of PKA-dependent control of LCRs and beating rate beyond that in the basal state. The link between SR Ca2+ cycling and beating rate is also present in vivo, as the regulation of beating rate by local beta-adrenergic receptor stimulation of the sinoatrial node in intact dogs is markedly blunted when SR Ca2+ cycling is disrupted by ryanodine. Thus, PKA-dependent phosphorylation of proteins that regulate cell Ca2+ balance and spontaneous SR Ca2+ cycling, ie, phospholamban and L-type Ca2+ channels (and likely others not measured in this study), controls the phase and size of LCRs and the resultant Na+-Ca2+ exchanger current and is crucial for both basal and reserve cardiac pacemaker function. C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Univ N Texas, Hlth Sci Ctr, Dept Integrat Physiol, Ft Worth, TX USA. Univ N Texas, Hlth Sci Ctr, Inst Cardiovasc Res, Ft Worth, TX USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU Intramural NIH HHS NR 20 TC 155 Z9 159 U1 0 U2 12 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 MAR 3 PY 2006 VL 98 IS 4 BP 505 EP 514 DI 10.1161/01.RES.0000204575.94040.d1 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 017YD UT WOS:000235728300015 PM 16424365 ER PT J AU Choudhary, S Doherty, KM Handy, CJ Sayer, JM Yagi, H Jerina, DM Brosh, RM AF Choudhary, S Doherty, KM Handy, CJ Sayer, JM Yagi, H Jerina, DM Brosh, RM TI Inhibition of Werner syndrome helicase activity by benzo[a]pyrene diol epoxide adducts can be overcome by replication protein A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 7,8-DIOL 9,10-EPOXIDE ADDUCTS; CODON 61 SEQUENCE; DNA DUPLEX; SYNDROME CELLS; SOLUTION CONFORMATION; HOMOLOGOUS RECOMBINATION; MODIFIED DEOXYGUANOSINE; TRANSLESION SYNTHESIS; RECQ HELICASES; WRN HELICASE AB RecQ helicases are believed to function in repairing replication forks stalled by DNA damage and may also play a role in the intra-S-phase checkpoint, which delays the replication of damaged DNA, thus permitting repair to occur. Since little is known regarding the effects of DNA damage on RecQ helicases, and because the replication and recombination defects in Werner syndrome cells may reflect abnormal processing of damaged DNA associated with the replication fork, we examined the effects of specific bulky, covalent adducts at N-6 of deoxyadenosine (dA) or N-2 of deoxyguanosine (dG) on Werner (WRN) syndrome helicase activity. The adducts are derived from the optically active 7,8-diol 9,10-epoxide (DE) metabolites of the carcinogen benzo[a]pyrene (BaP). The results demonstrate that WRN helicase activity is inhibited in a strand-specific manner by BaP DE-dG adducts only when on the translocating strand. These adducts either occupy the minor groove without significant perturbation of DNA structure (trans adducts) or cause base displacement at the adduct site (cis adducts). In contrast, helicase activity is only mildly affected by intercalating BaP DE-dA adducts that locally perturb DNA double helical structure. This differs from our previous observation that intercalating dA adducts derived from benzo[c]phenanthrene (BcPh) DEs inhibit WRN activity in a strand-and stereospecific manner. Partial unwinding of the DNA helix at BaP DE-dA adduct sites may make such adducted DNAs more susceptible to the action of helicase than DNA containing the corresponding BcPh DE-dA adducts, which cause little or no destabilization of duplex DNA. The single-stranded DNA binding protein RPA, an auxiliary factor for WRN helicase, enabled the DNA unwinding enzyme to overcome inhibition by either the trans-R or cis-R BaP DE-dG adduct, suggesting that WRN and RPA may function together to unwind duplex DNA harboring specific covalent adducts that otherwise block WRN helicase acting alone. C1 NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIA, Lab Mol Gerontol, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM broshr@grc.nia.nih.gov FU Intramural NIH HHS NR 69 TC 14 Z9 14 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 MAR 3 PY 2006 VL 281 IS 9 BP 6000 EP 6009 DI 10.1074/jbc.M510122200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 015RQ UT WOS:000235568900081 PM 16380375 ER PT J AU Ito, Y Goto, T Yamada, S Matsumoto, H Oka, H Takahashi, N Nakazawa, H Nagase, H Ito, Y AF Ito, Y Goto, T Yamada, S Matsumoto, H Oka, H Takahashi, N Nakazawa, H Nagase, H Ito, Y TI Application of dual counter-current chromatography for rapid sample preparation of N-methylcarbamate pesticides in vegetable oil and citrus fruit SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE dual counter-current chromatography; carbaryl; fenobucarb; methomyl; citrus fruit ID WATER FREE; BACITRACIN; ADDITIVES; NITROGEN; SEPARATION AB Dual counter-current chromatography (dual CCC) has been successfully applied to rapid sample preparation for the simultaneous determination of residual carbaryl, fenobucarb and methomyl in vegetable oil and citrus fruit. The citrus fruit samples were extracted with n-hexane Solution containing stable isotopically labeled internal standards (methomyl-d3, fenobucarb-d3 and carbaryl-d9), and applied to dual CCC using a two-phase solvent system of n-hexane-acetonitrile to purify the carbamate pesticides from aliphatic sample matrix. The coiled column was rotated at 420 rpm, the lower mobile phase was introduced through the head toward the tail. and the upper mobile phase in the opposite direction. Due to the high partition efficiency of dual CCC, the lower phase fraction collected from 2 to 5 min after injection could be subjected to flow-injection tandem mass spectrometry directly after concentration. Repetitive sample injection can be performed at high reproducibility without a risk of contamination from the compounds retained in the column. (c) 2006 Elsevier B.V. All rights reserved. C1 Aichi Prefectural Inst Publ Hlth, Kita Ku, Nagoya, Aichi 4628576, Japan. Kinjo Gakuin Univ, Moriyama Ku, Nagoya, Aichi 4638521, Japan. Hoshi Univ, Shinagawa Ku, Tokyo 1428501, Japan. Gifu Pharmaceut Univ, Gifu 5028585, Japan. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Ito, Y (reprint author), Aichi Prefectural Inst Publ Hlth, Kita Ku, Tsuji Machi, Nagoya, Aichi 4628576, Japan. EM yuuko_1_itou@pref.aichi.lg.jp NR 11 TC 23 Z9 29 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 3 PY 2006 VL 1108 IS 1 BP 20 EP 25 DI 10.1016/j.chroma.2005.12.070 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 015VA UT WOS:000235578100004 PM 16445929 ER PT J AU Manoussaki, D Dimitriadis, EK Chadwick, RS AF Manoussaki, D Dimitriadis, EK Chadwick, RS TI Cochlea's graded curvature effect on low frequency waves SO PHYSICAL REVIEW LETTERS LA English DT Article ID BASILAR-MEMBRANE; COILED COCHLEA; COILING; MOTION AB In the ear, sound waves are processed by a membrane of graded mechanical properties that resides in the fluid-filled spiral cochlea. The role of stiffness grading as a Fourier analyzer is well known, but the role of the curvature has remained elusive. Here, we report that increasing curvature redistributes wave energy density towards the cochlea's outer wall, affecting the shape of waves propagating on the membrane, particularly in the region where low frequency sounds are processed. C1 Vanderbilt Univ, Dept Math, Nashville, TN 37240 USA. NIH, Div Bioengn & Phys Sci, ORS OD, Bethesda, MD 20892 USA. NIDCD, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. RP Manoussaki, D (reprint author), Vanderbilt Univ, Dept Math, Nashville, TN 37240 USA. NR 12 TC 23 Z9 25 U1 0 U2 5 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 MAR 3 PY 2006 VL 96 IS 8 AR 088701 DI 10.1103/PhysRevLett.96.088701 PG 4 WC Physics, Multidisciplinary SC Physics GA 018AX UT WOS:000235736200082 PM 16606236 ER PT J AU Grover, AC Tangrea, MA Woodson, KG Wallis, BS Hanson, JC Chuaqui, RF Gillespie, JW Erickson, HS Bonner, RF Pohida, TJ Emmert-Buck, MR Libutti, SK AF Grover, AC Tangrea, MA Woodson, KG Wallis, BS Hanson, JC Chuaqui, RF Gillespie, JW Erickson, HS Bonner, RF Pohida, TJ Emmert-Buck, MR Libutti, SK TI Tumor-associated endothelial cells display GSTP1 and RAR beta 2 promoter methylation in human prostate cancer SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID EPIGENETIC CHANGES; STROMAL CELLS; GENES AB Background: A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. Methods: Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RAR beta 2 promoters via the QMS-PCR method. Results: Comparing GSTP1 and RAR beta 2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. Conclusion: We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pathologenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM grovera@mail.nih.gov; tangream@mail.nih.gov; woodsonk@dcpcepn.nci.nih.gov; wallisb@mail.nih.gov; hansoje@mail.nih.gov; chuaquir@mail.nih.gov; jgill@mail.nih.gov; ericksoh@mail.nih.gov; bonnerr@mail.nih.gov; pohidat@exchange.nih.gov; buckm@mail.nih.gov; libuttis@mail.nih.gov RI Bonner, Robert/C-6783-2015 NR 12 TC 27 Z9 30 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD MAR 2 PY 2006 VL 4 AR 13 DI 10.1186/1479-5876-4-13 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 026ZH UT WOS:000236381700002 PM 16512911 ER PT J AU Martin, W Koonin, EV AF Martin, W Koonin, EV TI Introns and the origin of nucleus-cytosol compartmentalization SO NATURE LA English DT Article ID EUKARYOTIC EVOLUTION; SPLICEOSOMAL INTRONS; MAMMALIAN-CELLS; EXON THEORY; RNA DECAY; GENES; TRANSLATION; COMPLEX; PIECES; LIFE AB The origin of the eukaryotic nucleus marked a seminal evolutionary transition. We propose that the nuclear envelope's incipient function was to allow mRNA splicing, which is slow, to go to completion so that translation, which is fast, would occur only on mRNA with intact reading frames. The rapid, fortuitous spread of introns following the origin of mitochondria is adduced as the selective pressure that forged nucleus - cytosol compartmentalization. C1 Univ Dusseldorf, Inst Bot 3, 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 3, D-40225 Dusseldorf, Germany. EM w.martin@uni-duesseldorf.de RI Martin, William/C-5680-2008; Martin, William /O-5446-2015 OI Martin, William /0000-0003-1478-6449 FU Intramural NIH HHS NR 57 TC 269 Z9 277 U1 5 U2 46 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 2 PY 2006 VL 440 IS 7080 BP 41 EP 45 DI 10.1038/nature04531 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 017HW UT WOS:000235685700034 PM 16511485 ER PT J AU Tildesley, MJ Savill, NJ Shaw, DJ Deardon, R Brooks, SP Woolhouse, MEJ Grenfell, BT Keeling, MJ AF Tildesley, MJ Savill, NJ Shaw, DJ Deardon, R Brooks, SP Woolhouse, MEJ Grenfell, BT Keeling, MJ TI Optimal reactive vaccination strategies for a foot-and-mouth outbreak in the UK SO NATURE LA English DT Article ID GREAT-BRITAIN; CONTROL POLICIES; EPIDEMIC; DISEASE; TRANSMISSION; PROGRAMS; SPREAD; DESIGN; IMPACT AB Foot-and-mouth disease (FMD) in the UK provides an ideal opportunity to explore optimal control measures for an infectious disease. The presence of fine-scale spatio-temporal data for the 2001 epidemic has allowed the development of epidemiological models that are more accurate than those generally created for other epidemics(1-5) and provide the opportunity to explore a variety of alternative control measures. Vaccination was not used during the 2001 epidemic; however, the recent DEFRA ( Department for Environment Food and Rural Affairs) contingency plan(6) details how reactive vaccination would be considered in future. Here, using the data from the 2001 epidemic, we consider the optimal deployment of limited vaccination capacity in a complex heterogeneous environment. We use a model of FMD spread to investigate the optimal deployment of reactive ring vaccination of cattle constrained by logistical resources. The predicted optimal ring size is highly dependent upon logistical constraints but is more robust to epidemiological parameters. Other ways of targeting reactive vaccination can significantly reduce the epidemic size; in particular, ignoring the order in which infections are reported and vaccinating those farms closest to any previously reported case can substantially reduce the epidemic. This strategy has the advantage that it rapidly targets new foci of infection and that determining an optimal ring size is unnecessary. C1 Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. Univ Warwick, Math Inst, Coventry CV4 7AL, W Midlands, England. Univ Cambridge, Ctr Math Sci, Stat Lab, Cambridge CB3 0WB, England. Univ Edinburgh, Ashworth Labs, Ctr Infect Dis, Epidemiol Grp, Edinburgh EH9 3JF, Midlothian, Scotland. Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush Vet Ctr, Roslin EH25 9RG, Midlothian, Scotland. Univ Cambridge, Ctr Vet Sci, Cambridge Infect Dis Consortium, Cambridge CB3 0ES, England. Penn State Univ, Mueller Lab, Biol Dept 208, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Keeling, MJ (reprint author), Univ Warwick, Dept Biol Sci, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. EM m.j.keeling@warwick.ac.uk RI Tildesley, Michael/B-6559-2008; Keeling, Matt/J-9280-2012; OI Keeling, Matt/0000-0003-4639-4765 FU Wellcome Trust NR 16 TC 121 Z9 123 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 2 PY 2006 VL 440 IS 7080 BP 83 EP 86 DI 10.1038/nature04324 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 017HW UT WOS:000235685700044 PM 16511494 ER PT J AU Ramiro, AR Jankovic, M Callen, E Difilippantonio, S Chen, HT McBride, KM Eisenreich, TR Chen, JJ Dickins, RA Lowe, SW Nussenzweig, A Nussenzweig, MC AF Ramiro, AR Jankovic, M Callen, E Difilippantonio, S Chen, HT McBride, KM Eisenreich, TR Chen, JJ Dickins, RA Lowe, SW Nussenzweig, A Nussenzweig, MC TI Role of genomic instability and p53 in AID-induced c-myc-Igh translocations SO NATURE LA English DT Article ID CLASS-SWITCH RECOMBINATION; CYTIDINE DEAMINASE AID; URACIL-DNA GLYCOSYLASE; CHROMOSOMAL TRANSLOCATIONS; SOMATIC HYPERMUTATION; DEFICIENT MICE; B-CELLS; ACTIVATION; REGIONS; 53BP1 AB Chromosomal translocations involving the immunoglobulin switch region are a hallmark feature of B-cell malignancies(1). However, little is known about the molecular mechanism by which primary B cells acquire or guard against these lesions. Here we find that translocations between c-myc and the IgH locus (Igh) are induced in primary B cells within hours of expression of the catalytically active form of activation-induced cytidine deaminase (AID), an enzyme that deaminates cytosine to produce uracil in DNA(2,3). Translocation also requires uracil DNA glycosylase (UNG), which removes uracil from DNA to create abasic sites that are then processed to double-strand breaks(4,5). The pathway that mediates aberrant joining of c-myc and Igh differs from intrachromosomal repair during immunoglobulin class switch recombination in that it does not require histone H2AX(6), p53 binding protein 1 ( 53BP1)(7,8) or the non-homologous end-joining protein Ku80(9). In addition, translocations are inhibited by the tumour suppressors ATM, Nbs1, p19 (Arf) and p53, which is consistent with activation of DNA damage- and oncogenic stress-induced checkpoints during physiological class switching. Finally, we demonstrate that accumulation of AID-dependent, IgH-associated chromosomal lesions is not sufficient to enhance c-myc-Igh translocations. Our findings reveal a pathway for surveillance and protection against AID-dependent DNA damage, leading to chromosomal translocations. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY 10021 USA. Mayo Clin, Div Oncol, Rochester, MN 55905 USA. Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov; nussen@mail.rockefeller.edu RI mcbride, kevin/E-8230-2011; Dickins, Ross/K-2852-2012; Ramiro, Almudena/H-6037-2015 OI Dickins, Ross/0000-0003-4112-5304; Ramiro, Almudena/0000-0002-7539-3844 FU Intramural NIH HHS; NCI NIH HHS [P30 CA008748, P01 CA013106] NR 30 TC 215 Z9 221 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 2 PY 2006 VL 440 IS 7080 BP 105 EP 109 DI 10.1038/nature04495 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 017HW UT WOS:000235685700049 PM 16400328 ER PT J AU Yousry, TA Major, EO Ryschkewitsch, C Fahle, G Fischer, S Hou, J Curfman, B Miszkiel, K Mueller-Lenke, N Sanchez, E Barkhof, F Radue, EW Jager, HR Clifford, DB AF Yousry, TA Major, EO Ryschkewitsch, C Fahle, G Fischer, S Hou, J Curfman, B Miszkiel, K Mueller-Lenke, N Sanchez, E Barkhof, F Radue, EW Jager, HR Clifford, DB TI Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID JC VIRUS-DNA; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; CROHNS-DISEASE; THERAPY AB Background: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. Methods: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. Results: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). Conclusions: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known. C1 Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. Inst Neurol, London WC1N 3BG, England. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD USA. Univ Basel, Dept Neuroradiol, Basel, Switzerland. Vrije Univ Amsterdam, Med Ctr, Dept Radiol, Amsterdam, Netherlands. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Major, EO (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, 10 Ctr Dr,Bldg 10,Rm 3B14, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov RI Yousry, Tarek/B-3417-2009; Jager, Hans Rolf/K-1868-2013 OI Jager, Hans Rolf/0000-0002-6403-4184 FU Intramural NIH HHS; Multiple Sclerosis Society [748] NR 16 TC 477 Z9 495 U1 2 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 2 PY 2006 VL 354 IS 9 BP 924 EP 933 DI 10.1056/NEJMoa054693 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 017FN UT WOS:000235679600005 PM 16510746 ER PT J AU Zerhouni, EA AF Zerhouni, EA TI Translational and clinical science - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 2 PY 2006 VL 354 IS 9 BP 978 EP 979 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 017FN UT WOS:000235679600029 ER PT J AU Wang, Y Zhang, Z Yao, R Jia, D Wang, D Lubet, RA You, M AF Wang, Y Zhang, Z Yao, R Jia, D Wang, D Lubet, RA You, M TI Prevention of lung cancer progression by bexarotene in mouse models SO ONCOGENE LA English DT Article DE chemoprevention; bexarotene; lung cancer; mouse models ID RETINOID-X-RECEPTOR; SELECTIVE LIGAND LGD1069; MAMMARY-CARCINOMA; TARGRETIN; MICE; CHEMOPREVENTION; TAMOXIFEN; EFFICACY; MUTATION; TUMORS AB Bexarotene (Targretin((R)), Ligand Pharmaceuticals Inc.) is a synthetic high-affinity RXR receptor agonist with limited affinity for RAR receptors. Bexarotene has shown efficacy in a phase I/II trial of non-small-cell lung cancers. However, the chemopreventive efficacy of bexarotene has not been determined in mouse lung cancer models. In this study, we have investigated the ability of bexarotene to inhibit lung tumor progression in the mutant A/J mouse models with genetic alterations in p53 or K-ras, two of the most commonly altered genes in human lung tumorigenesis. Mice were administered vinyl carbamate ( VC), a carcinogen, by a single intraperitoneal injection (i.p.) at 6 weeks of age. Bexarotene was given by gavage starting at 16 weeks after VC and was continued for 12 weeks. Although all mice developed lung tumors, only 7% of lung tumors were adenocarcinomas in wild-type mice, whereas 22 and 26% of lung tumors were adenocarcinomas in p53 transgenic or K-ras heterozygous deficient mice. Bexarotene inhibited both tumor multiplicity and tumor volume in mice of all three genotypes. Furthermore, bexarotene reduced the progression of adenoma to adenocarcinoma by similar to 50% in both p53(wt/wt)K-ras(ko/wt) and p53(wt/wt)K-ras(wt/wt) mice. Thus, bexarotene appears to be an effective preventive agent against lung tumor growth and progression. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA. Chemoprevent Agent Dev Res Grp, NCI, Rockville, MD USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [N01CN25104, R01CA58554] NR 32 TC 21 Z9 21 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 2 PY 2006 VL 25 IS 9 BP 1320 EP 1329 DI 10.1038/sj.onc.1209180 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 017QN UT WOS:000235708200005 PM 16247446 ER PT J AU Gallas, BD AF Gallas, BD TI One-shot estimate of MRMC variance: AUC SO ACADEMIC RADIOLOGY LA English DT Article DE MRMC; ROC; AUC; variance; reader variability; case variability; jackknife; ANOVA; bootstrap ID OPERATING CHARACTERISTIC CURVES; MAXIMUM-LIKELIHOOD ESTIMATION; SIGNAL-DETECTION THEORY; DORFMAN-BERBAUM-METZ; NONPARAMETRIC APPROACH; ROC ANALYSIS; MULTIREADER; AREA; VARIABILITY; VALIDATION AB Rationale and Objectives. One Popular study design for estimating the area under the receiver operating characteristic curve (AUC) is the one in which a set of readers reads a set of cases: a fully crossed design in which every reader reads every case. The variability of the subsequent reader-averaged AUC has two sources: the multiple readers and the multiple cases (MRMC). In this article, we present a nonparametric estimate for the variance of the reader-averaged AUC that is unbiased and does not use resampling tools. Materials and Methods. The one-shot estimate is based on the MRMC variance derived by the mechanistic approach of Barrett et al. (2005), as well as the nonparametric variance of a single-reader AUC derived in the literature on U statistics. We investigate the bias and variance properties of the one-shot estimate through a set of Monte Carlo simulations with simulated model observers and images. The different simulation configurations vary numbers of readers and cases, amounts of image noise and internal noise, as well as how the readers are constructed. We compare the one-shot estimate to a method that uses the jackknife resampling technique with an analysis of variance model at its foundation (Dorfman et al. 1992). The name one-shot highlights that resampling is not used. Results. The one-shot and jackknife estimators behave similarly, with the one-shot being marginally more efficient when the number of cases is small. Conclusions. We have derived a one-shot estimate of the MRMC variance of AUC that is based on a probabilistic foundation with limited assumptions, is unbiased, and compares favorably to an established estimate. C1 US FDA, CDRH, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Gallas, BD (reprint author), US FDA, CDRH, NIBIB CDRH Lab Assessment Med Imaging Syst, Bldg 1,HFZ-140,12720 Twinbrook Pkwy,Rm 158, Rockville, MD 20852 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 34 TC 68 Z9 68 U1 0 U2 4 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2006 VL 13 IS 3 BP 353 EP 362 DI 10.1016/j.acra.2005.11.030 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 020QO UT WOS:000235925100011 PM 16488848 ER PT J AU Stefan, H da Silva, FHL Loscher, W Schmidt, D Perucca, E Brodie, MJ Boon, PAJM Theodore, WH Moshe, SL AF Stefan, H da Silva, FHL Loscher, W Schmidt, D Perucca, E Brodie, MJ Boon, PAJM Theodore, WH Moshe, SL TI Epileptogenesis and rational therapeutic strategies SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Review DE epileptogenesis; rational treatment; neurobiological mechanisms; molecular biology; evidence ID TEMPORAL-LOBE EPILEPSY; 1ST UNPROVOKED SEIZURE; TONIC-CLONIC SEIZURE; ACID DECARBOXYLASE AUTOANTIBODIES; MEDICALLY INTRACTABLE EPILEPSY; ACADEMY-OF-NEUROLOGY; EXTENDED FOLLOW-UP; ANTIEPILEPTIC DRUGS; REFRACTORY EPILEPSY; GLUTAMATE-RECEPTOR AB The understanding of neurobiological mechanisms of epileptogenesis is essential for rational approaches for a possible disease modification as well as treatment of underlying causes of the epilepsies. More effort is necessary to translate results from basic investigations into new approaches for clinical research and to better understand a relationship with findings from clinical studies. The following report is a condensed synapsis in which molecular mechanisms of epileptogenesis, pharmacological modulation of epileptogenesis, evidence based therapy, refractoriness and prediction of outcome is provided in order to stimulate further collaborative international research. C1 Univ Erlangen Nurnberg, Neurol Clin, Epilepsy Ctr, D-91054 Erlangen, Germany. Univ Amsterdam, Ctr Neurosci, Swammerdam Inst Life Sci, Amsterdam, Netherlands. Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Hannover, Germany. Ctr Syst Neurosci, Hannover, Germany. Epilepsy Res Grp, Berlin, Germany. IRCCS, Inst Neurol, C Mondino Fdn, Pavia, Italy. Univ Pavia, Clin Pharmacol Unit, Dept Internal Med & Therapeut, I-27100 Pavia, Italy. Univ Glasgow, Epilepsy Unit, Glasgow, Lanark, Scotland. Ghent Univ Hosp, Dept Neurol, Reference Ctr Refractory Epilepsy, B-9000 Ghent, Belgium. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Neurol, Montefiore Med Ctr, New York, NY USA. Albert Einstein Coll Med, Dept Neurosci & Pediat, Montefiore Med Ctr, New York, NY USA. Albert Einstein Coll Med, Comprehens Epilepsy Management Ctr, Montefiore Med Ctr, New York, NY USA. RP Stefan, H (reprint author), Univ Erlangen Nurnberg, Neurol Clin, Epilepsy Ctr, Schwabachanlage 6, D-91054 Erlangen, Germany. EM hermann.stefan@neuro.imed.uni-erlangen.de NR 92 TC 28 Z9 30 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-6314 EI 1600-0404 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD MAR PY 2006 VL 113 IS 3 BP 139 EP 155 DI 10.1111/j.1600-0404.2005.00561.x PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 006SP UT WOS:000234917700001 PM 16441243 ER PT J AU Raju, TNK AF Raju, TNK TI Emil Adolf von Behring and serum therapy for diphtheria SO ACTA PAEDIATRICA LA English DT Biographical-Item C1 NICHD, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), NICHD, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 1 TC 2 Z9 5 U1 2 U2 7 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD MAR PY 2006 VL 95 IS 3 BP 258 EP 259 DI 10.1080/08035250600580586 PG 2 WC Pediatrics SC Pediatrics GA 014SL UT WOS:000235500100001 PM 16497632 ER PT J AU Joshi, S Dutta, S Bell, B Profy, A Kuruc, J Fang, G Maslankowski, L Soto-Torres, L Panchanadikar, A Reynolds, SJ AF Joshi, S Dutta, S Bell, B Profy, A Kuruc, J Fang, G Maslankowski, L Soto-Torres, L Panchanadikar, A Reynolds, SJ CA HPTN 047 Protocol Team TI Documenting intermenstrual bleeding in a vaginal microbicide study: Case reports and lessons learned SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter ID WOMEN C1 Natl AIDS Res Inst, MIDC, Pune 411026, Maharashtra, India. Family Hlth Int, Res Triangle Pk, NC 27709 USA. Indevus Pharmaceut, Lexington, MA USA. Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA. Univ Penn, Sch Med, University City, PA USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Joshi, S (reprint author), Natl AIDS Res Inst, MIDC, G-73,POB 1895, Pune 411026, Maharashtra, India. EM sjoshi@nariindia.org NR 6 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2006 VL 22 IS 3 BP 294 EP 296 DI 10.1089/aid.2006.22.294 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 028WS UT WOS:000236520100011 PM 16545017 ER PT J AU Lorenz, JG Long, JC Linnoila, M Goldman, D Suomi, SJ Higley, JD AF Lorenz, JG Long, JC Linnoila, M Goldman, D Suomi, SJ Higley, JD TI Genetic and other contributions to alcohol intake in rhesus Macaques (Macaca mulatta) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE heritability; alcohol consumption; additive genetic effects ID NONHUMAN PRIMATE MODEL; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; DIMINISHED SOCIAL COMPETENCE; CEREBROSPINAL-FLUID; EARLY EXPERIENCE; CONSUMPTION PATTERNS; MONKEYS; SEROTONIN; TWIN; STRESS AB Background: The etiology of alcoholism and alcohol abuse, like many other complex diseases, is heterogeneous and multifactorial. Numerous studies demonstrate a genetic contribution to variation in the expression of alcohol-related disorders in humans. Over the past decade, nonhuman primates have emerged as a valuable model for some aspects of human alcohol abuse because of their phylogenetic proximity to humans. Long-term, longitudinal studies of rhesus macaques (Macaca mulatta) have provided much insight into environmental influences, especially early life experiences, on alcohol consumption and behavior patterns that characterize alcohol intake later in life. It is not known, however, whether there is a genetic component as well to the variation seen in alcohol consumption in rhesus macaques. A significant genetic component to variation in alcohol consumption in rhesus macaques would show for the first time that like humans, for nonhuman primates additive genetic influences are important. Moreover, their use as a model for alcohol-related disorders in humans would have even greater relevance and utility for designing experiments incorporating the expanding molecular genetics field, and allow researchers to investigate the interaction among the known environmental influences and various genotypes. Methods: In this study, we investigate factors contributing to variation in alcohol consumption of 156 rhesus macaques collected over 10 years when subjects were adolescent in age, belonging to a single extended pedigree, with each cohort receiving identical early rearing backgrounds and subsequent treatments. To measure alcohol consumption each animal was provided unfettered simultaneous access both to an aspartame-sweetened 8.4% (v/v) alcohol-water solution, the aspartame-sweetened vehicle, and to water for I hour each day during the early afternoon between 13:00 and 15:00 in their home cages for a period of 5 to 7 weeks. We use multiple regression to identify factors that significantly affect alcohol consumption among these animals and a maximum likelihood program (ASReml) that, controlling for the significant factors, estimates the genetic contribution to the variance in alcohol consumption. Results: Multiple regression analysis identified test cohort and rearing environment as contributing to 57 and 2%, respectively, of the total variance in alcohol consumption. Of the remaining 41% of the variance about half (19.8%) was attributable to additive genetic effects using a maximum likelihood program. Conclusion: This study demonstrates that, as in humans, there are additive genetic factors that contribute to variation in alcohol consumption in rhesus macaques, with other nongenetic factors accounting for substantial portions of the variance in alcohol consumption, Our findings show the presence of an additive genetic component and suggest the potential utility of the nonhuman primate as a molecular genetics tool for understanding alcohol abuse and alcoholism. C1 Coriell Inst Med Res, Mol Biol Lab, Camden, NJ 08103 USA. Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ctr Stat Genet, Ann Arbor, MI USA. NIAAA, Sect Study Primate Models Psychopathol, LCTS, NIH, Poolesville, MD USA. NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Lorenz, JG (reprint author), Coriell Inst Med Res, Mol Biol Lab, 403 Haddon Ave, Camden, NJ 08103 USA. EM jlorenz@coriell.umdnj.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU Intramural NIH HHS NR 50 TC 10 Z9 10 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2006 VL 30 IS 3 BP 389 EP 398 DI 10.1111/j.1530-0277.2006.00044.x PG 10 WC Substance Abuse SC Substance Abuse GA 019EB UT WOS:000235817300001 PM 16499479 ER PT J AU Enoch, MA Waheed, JF Harris, CR Albaugh, B Goldman, D AF Enoch, MA Waheed, JF Harris, CR Albaugh, B Goldman, D TI Sex differences in the influence of COMT Val158Met on alcoholism and smoking in plains American Indians SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE genes; polymorphism; haplotype; harm avoidance; nicotine ID CATECHOL-O-METHYLTRANSFERASE; POPULATION-BASED SAMPLE; FUNCTIONAL VARIANT; REGULAR SMOKERS; DOWN-REGULATION; ENZYME-ACTIVITY; FEMALE TWINS; ASSOCIATION; GENE; POLYMORPHISM AB Background: Alcoholism and heavy smoking are highly comorbid and are cotransmitted in the general U.S. population; however little is known about comorbidity in American Indians. The catechol-O-methyltransferase (COMT) functional polymorphism, Val158Met, has been associated with alcoholism in Caucasians. The aims of our study were firstly to investigate patterns of alcohol and tobacco consumption and comorbidity between alcoholism and smoking in Plains American Indians and secondly to determine the influence, including sexual dimorphic effects, of COMT Val158Met and COMT haplotypes, on these behaviors. Methods: Diagnostic and Statistical Manual-III-R lifetime diagnoses were assigned to 342 community-ascertained Plains American Indians (201 women, 141 men). Lifetime drinking and smoking histories were obtained. Five COMT loci, including Val158Met, were genotyped. Haplotype-based analyses identified 1 block with 3 common haplotypes; 2 included Val158, and I had the Met158 allele. Results: The alcoholics drank heavily (12 +/- 8 drinks/drinking day) but episodically (max 10 +/- 8 d/mo). Although 62% of male alcoholics and 40% of female alcoholics were smokers (>= 10 cigarettes/d), only 12% of alcoholic men and 8% of alcoholic women smoked heavily (> 20/d). In women, the COMT Val158 allele frequency was maximal in alcoholic smokers (0.85), decreasing to 0.74 in nonalcoholic smokers, 0.67 in alcoholic nonsmokers, and 0.64 in nonalcoholic nonsmokers (chi(2) = 11.1, 3 df, p = 0.011). Women showed a main effect of Val158 on smoking (p = 0.003). Both male and female alcoholics were more likely to have at least 1 Val158 allele compared with nonalcoholics (0.95 vs 0.88, p < 0.05). Approximately 30% of all participants were long-term, nonaddicted light, social smokers (3.6 +/- 1.7 cigarettes/d); they had the same Val158Met frequencies as nonsmokers. Haplotype analyses supported the Val158Met findings; however, only 1 of the 2 Val158 haplotypes was implicated. Conclusions: Plains Indians have different smoking and drinking patterns and considerably less comorbidity between alcoholism and heavy smoking compared with the general U.S. population. Our COMT Val158Met results suggest that there may be both sex differences in the genetic origins of alcoholism and smoking in this population and overlap in genetic vulnerability to both addictions in women. C1 NIAAA, DICBR, LNG, NIH, Bethesda, MD 20892 USA. Crt Human Behav Studies Inc, Weatherford, OK USA. RP Enoch, MA (reprint author), NIAAA, DICBR, LNG, NIH, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 47 TC 46 Z9 47 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2006 VL 30 IS 3 BP 399 EP 406 DI 10.1111/j.1530-0277.2006.00045.x PG 8 WC Substance Abuse SC Substance Abuse GA 019EB UT WOS:000235817300002 PM 16499480 ER PT J AU Lewis, EF Hellkamp, AS Pfeffer, MA Greenspon, AJ Machado, C Singh, S Schron, E Lee, KL Lamas, GA AF Lewis, EF Hellkamp, AS Pfeffer, MA Greenspon, AJ Machado, C Singh, S Schron, E Lee, KL Lamas, GA TI The association of the heart failure score with mortality and heart failure hospitalizations in elderly patients: Insights from the Mode Selection Trial (MOST) SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SINUS-NODE DYSFUNCTION; POPULATION; SURVIVAL; PROGNOSIS AB Background Patient and physician preferences as well as cost favor an increasingly higher threshold for hospital admission for heart failure (HF) treatment. This trend risks masking the severity and prevalence of HF as hospitalization for HF may decrease. Methods Heart Failure Score (HFS) has 4 ordinal subscales assessing (1) HF symptoms, physical signs of left (2) and (3) right HF, and (4) therapy changes for HF. Heart Failure Score was calculated for 1257 of 2010 (63%) patients enrolled in the MOST trial in sinus node dysfunction, who survived and had complete first-year HFS data at 4 postpacemaker implant visits (1, 3, 6, and 12 months). Heart Failure Score was summed and ranged from 0 to 14, with lower scores representing less HF. Results There were 1257 patients (median age 74 years [interquartile range 68.79], 47% were women, 61% had hypertension, 20%, diabetes mellitus, and 23%, prior myocardial infarction). The median HFS accumulated during 1 year was 4 (interquartile range 1-8). Of patients with a benign first year, those with a higher HFS were more likely to die during subsequent follow-up compared with patients with lower HFS (hazard ratio 1.07, 95% Cl 1.04-1.10 for each 1-point increase, P < .001). Conclusions Increasing HFS is associated with an increased risk of mortality in mostly elderly patients without pre-existing HF. Heart Failure Score maybe a useful surrogate HF end point for clinical trials. C1 Harvard Univ, Div Cardiovasc, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Duke Univ, Sch Med, Durham, NC USA. Duke Univ, Clin Res Ctr, Durham, NC USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Providence Hosp, Southfield, MI 48037 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Mt Sinai Med Ctr, Inst Heart, Miami Beach, FL 33140 USA. RP Lewis, EF (reprint author), Harvard Univ, Div Cardiovasc, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM eflewis@partners.org FU NHLBI NIH HHS [U01 HL53973, U01 HL 49804, 1 F32 HL71449-01] NR 22 TC 6 Z9 7 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2006 VL 151 IS 3 BP 699 EP 705 DI 10.1016/j.ahj.2005.05.018 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 026PF UT WOS:000236353900022 PM 16504635 ER PT J AU Gorelick, DA Heishman, SJ Preston, KL Nelson, RA Moolchan, ET Huestis, MA AF Gorelick, DA Heishman, SJ Preston, KL Nelson, RA Moolchan, ET Huestis, MA TI The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers SO AMERICAN HEART JOURNAL LA English DT Article ID ENDOGENOUS CANNABINOIDS; BLOOD-PRESSURE; HEART-RATE; DELTA-9-TETRAHYDROCANNABINOL; PERFORMANCE; MARIHUANA; CIRRHOSIS; BLOCKADE; MEDIATE; SYSTEM AB Background Animal studies suggest that cannabinoid CB1 receptors play a role in regulating blood pressure (BP). In human studies, activation of CB I receptors by cannabis or its active ingredient, Delta 9-tetrahydrocannabinol (THC), has modest and inconsistent effects on BP. Methods We evaluated this phenomenon in 63 male cannabis smokers (mean [SD] age 27.7 +/- 5.4 years, 70% African American, 10.3 +/- 5.9 years of lifetime cannabis use) by administering escalating oral doses (1, 3, 10, 30, 90 mg) of the selective CBI receptor antagonist rimonabant (or placebo) in a randomized, parallel-group, double-blind, placebocontrolled design. Subjects smoked an active (2.64% THC) or placebo marijuana cigarette 2 and 6 hours after rimonabont dosing. Blood pressure and symptoms were monitored for 90 minutes after smoking while subjects remained seated. Results Marijuana smoking alone (ie, after placebo rimonabant) had no consistent effect on BP, but 22% of subjects experienced symptomatic (dizziness, lightheadedness) hypotension, as did 20% to 33% of subjects who received pretreatment with rimonabant, 1, 3, or 10 mg. No subject receiving rimonabont, 30 or 90 mg, before marijuana smoking experienced symptomatic hypotension. The 7 subjects who experienced symptomatic hypotension had significantly higher mean (SD) peak plasma THC concentrations (181.6 +/- 80.2) than did the 33 subjects who did not (109.0 +/- 62.6). Rimonabont by itself had no effects on BP and did not alter THC pharmacokinetics. Conclusions These findings indicate that CB1 receptors play a role in mediating effects of cannabis smoking on BP in humans. C1 NIDA, Clin Pharmacol & Therapeut Branch, IRP, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), NIDA, Clin Pharmacol & Therapeut Branch, IRP, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@mail.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 23 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2006 VL 151 IS 3 AR 754.e1 DI 10.1016/j.ahj.2005.11.006 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 026PF UT WOS:000236353900033 ER PT J AU Wasson, K Cook, ED AF Wasson, K Cook, ED TI Pellegrino and medicine: A critical revision SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. Univ Oxford, Oxford OX1 2JD, England. RP Wasson, K (reprint author), NCI, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PD MAR-APR PY 2006 VL 6 IS 2 BP 90 EP 91 DI 10.1080/15265160500507132 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 017RC UT WOS:000235709700034 PM 16500869 ER PT J AU Saczynski, JS Pfeifer, LA Masaki, K Korf, ESC Laurin, D White, L Launer, LJ AF Saczynski, JS Pfeifer, LA Masaki, K Korf, ESC Laurin, D White, L Launer, LJ TI The effect of social engagement on incident dementia - The Honolulu-Asia Aging Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; Alzheimer disease; dementia; interpersonal relations; social behavior; social isolation ID JAPANESE-AMERICAN MEN; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; ENRICHED ENVIRONMENT; LEISURE ACTIVITIES; RISK; HIPPOCAMPAL; CALIFORNIA; DIAGNOSIS; NETWORK AB The authors examined whether low levels of social engagement in midlife and late life were associated with the risk of incident dementia in 2,513 Japanese-American men who have been followed since 1965 as part of the Honolulu Heart Program and the Honolulu-Asia Aging Study. In 1991, assessment of dementia began; incident dementia cases (n = 222) were diagnosed in 1994 and 1997. Social engagement was assessed in midlife (1968) and late life (1991). The relation between social engagement and dementia risk was examined using Cox proportional hazards models. No level of midlife social engagement was associated with the risk of dementia. In late life, compared with participants in the highest quartile of late-life social engagement, those in the lowest quartile had a significantly increased risk of dementia (hazard ratio = 2.34, 95% confidence interval: 1.18, 4.65). However, compared with those who were in the highest quartile of social engagement at both midlife and late life, only decreased social engagement from midlife to late life was associated with an increased risk of dementia (hazard ratio = 1.87, 95% confidence interval: 1.12, 3.13). Although low social engagement in late life is associated with risk of dementia, levels of late-life social engagement may already have been modified by the dementing process and may be associated with prodromal dementia. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Hawaii Manoa, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. Pacific Hlth Res Inst, Honolulu, HI USA. Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands. RP Saczynski, JS (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Gateway Bldg,Room 3C-309, Bethesda, MD 20892 USA. EM saczynsj@mail.nih.gov FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 27 TC 99 Z9 105 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2006 VL 163 IS 5 BP 433 EP 440 DI 10.1093/aje/kwj061 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 016ET UT WOS:000235604200005 PM 16410348 ER PT J AU Foltz, LM Dalal, BI Wadsworth, LD Broady, R Chi, K Eisenhauer, E Kobayashi, K Kollmannsburger, C AF Foltz, LM Dalal, BI Wadsworth, LD Broady, R Chi, K Eisenhauer, E Kobayashi, K Kollmannsburger, C TI Recognition and management of methemoglobinemia and hemolysis in a G6PD-deficient patient on experimental anticancer drug triapine SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE severe methemoglobinemia; experimental anti-cancer drug; Triapine; hemolysis; G6PD deficiency; G6PD screening AB We report occurrence of severe methemoglobinemia in a patient on novel experimental anti-cancer drug, Triapine. Treatment with methylene blue led to massive hemolysis due to concomitant G6PD deficiency. We recommend that G6PD screening be done in high-risk populations prior to commencement of Triapine therapy. C1 Vancouver Gen Hosp, Div Hematopathol, Vancouver, BC V5Z 1M9, Canada. Vancouver Gen Hosp, Div Hematol, Vancouver, BC V5Z 1M9, Canada. British Columbia Childrens & Womens Hosp, Div Hematopathol, Vancouver, BC, Canada. Univ British Columbia, British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 1M9, Canada. NCI, Canada Clin Trials Grp, Kingston, ON, Canada. NCI, Rockville, MD USA. RP Dalal, BI (reprint author), Vancouver Gen Hosp, Div Hematopathol, 855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. EM bakul.dalal@vch.ca NR 5 TC 22 Z9 23 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2006 VL 81 IS 3 BP 210 EP 211 DI 10.1002/ajh.20547 PG 2 WC Hematology SC Hematology GA 015RM UT WOS:000235568500011 PM 16493607 ER PT J AU Savani, PN Dunbar, CE Rick, ME AF Savani, PN Dunbar, CE Rick, ME TI Combination therapy with rFVIIa and platelets for hemorrhage in patients with severe thrombocytopenia and alloimmunization SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID FACTOR VIIA C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Hematol Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Savani, PN (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2006 VL 81 IS 3 BP 218 EP 219 DI 10.1002/ajh.20506 PG 2 WC Hematology SC Hematology GA 015RM UT WOS:000235568500016 ER PT J AU Rice, T Cooper, RS Wu, XD Bouchard, C Rankinen, T Rao, DC Jaquish, CE Fabsitz, RR Province, MA AF Rice, T Cooper, RS Wu, XD Bouchard, C Rankinen, T Rao, DC Jaquish, CE Fabsitz, RR Province, MA CA Natl Heart Lung & Blood Inst Gene TI Meta-analysis of genome-wide scans for blood pressure in African American and Nigerian samples SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE linkage; 2p14-2p13.1; 7p21.1-7p15.3; hypertension; African American ID LINKAGE ANALYSIS; HYPERTENSION; FAMILY; CHROMOSOME-2; GENES AB Background: In many genetic studies of complex traits, sample sizes are often too small to detect linkages of low-to-moderate effects. However, the combined linkage evidence across several studies can be synthesized using meta-analysis with the aim of providing more definitive support of linkage. Methods: In the current study using the National Heart Lung, and Blood Institute (NHLBI) GeneLink Project, a meta-analysis based on a modification of Fisher's method of pooling P values was used to investigate linkage for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values across three studies involving African American and Nigerian families (HyperGEN, Health, Risk Factors, Exercise Training and Genetics [HERITAGE], and Genetics of Hypertension in Blacks). Results: The meta results suggest two regions (2p and 7p) provide enhanced linkage evidence compared with the individual study results. The maximal meta Lod score of 2.9 on 2p14-p13.1 (64-78 cM) represented similar to 1-Lod unit increase over the respective individual study scores. This general region has been implicated previously involving primarily families of white ethnicity and provides confirmatory evidence that this QTL is common across ethnic groups. The second finding at 7p21.3-p15.3 (8-25 cM) provided a meta Lod of 3.5. Although region was implicated primarily in the Nigerian subjects the low-level but consistent support involving the African American families (individual Lod score of 1.0) suggests a novel QTL with respect to BP variation in individuals of black ethnicity. Conclusions: Follow-up studies involving positional cloning efforts of the combined families showing linkage evidence in these regions (particularly 2p) may be warranted to verify these findings and identify the genes and causative variants. C1 Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. NHLBI, Bethesda, MD 20892 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Loyola Univ, Med Ctr, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. RP Rice, T (reprint author), Washington Univ, Sch Med, Div Biostat, 660 S Euclid Ave,Box 8067, St Louis, MO 63110 USA. EM Treva@wubios.wustl.edu RI Rice, Treva/D-1385-2009; Bouchard, Claude/A-7637-2009 FU NHLBI NIH HHS [HL47317, HL54473]; NIGMS NIH HHS [GM028719] NR 15 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2006 VL 19 IS 3 BP 270 EP 274 DI 10.1016/j.amjhyper.2005.09.006 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 021LJ UT WOS:000235984400006 PM 16500512 ER PT J AU Muldoon, LL Tratnyek, PG Jacobs, PM Doolittle, ND Christoforidis, GA Frank, JA Lindau, M Lockman, PR Manninger, SP Qiang, Y Spence, AM Stupp, SI Zhang, M Neuwelt, EA AF Muldoon, LL Tratnyek, PG Jacobs, PM Doolittle, ND Christoforidis, GA Frank, JA Lindau, M Lockman, PR Manninger, SP Qiang, Y Spence, AM Stupp, SI Zhang, M Neuwelt, EA TI Imaging and nanomedicine for diagnosis and therapy in the central nervous system: Report of the eleventh annual blood-brain barrier disruption consortium meeting SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CONVECTION-ENHANCED DELIVERY; IN-VIVO; MALIGNANT GLIOMA; 8 T; NANOPARTICLES; CELLS; NANOFIBERS; TUMORS; MR; MODEL AB The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. The Eleventh Annual Blood-Brain Barrier Disruption Consortium Meeting was convened to discuss recent advances and future directions in imaging and nanomedicine. Two sessions, one on Cell and Molecular Imaging in the CNS and another on Nanotechnology, Nanobiology, and Nanomedicine, were held March 17-18, 2005, in Portland, Ore. CNS imaging presentations targeted differentiating tumor, neural lesions, and necrosis from healthy brain tissue; methods of delivery of imaging agents across the BBB; and new iron oxide-based nanoparticle contrast agents for MR imaging. Nanobiology presentations covered the development of new nanotechnology and its use in imaging, diagnosis, and therapy in the CNS. Discussions at this meeting stressed the role of biotechnology in the convergence of CNS imaging and nanomedicine and are summarized in this article. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Ohio State Univ, Columbus, OH 43210 USA. NIH, Expt Neuroimaging Sect, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY USA. NCI, Canc Imaging Program, Rockville, MD USA. Texas Tech Univ, Amarillo, TX USA. Univ Idaho, Moscow, ID 83843 USA. Univ Washington, Seattle, WA 98195 USA. Natl Inst Oncol, Budapest, Hungary. Northwestern Univ, Chicago, IL 60611 USA. RP Neuwelt, EA (reprint author), Oregon Hlth Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. RI Stupp, Samuel/B-6737-2009; Zhang, Miqin/F-5537-2010 OI Zhang, Miqin/0000-0001-8974-1494 FU NCI NIH HHS [4R13 CA 86959-05] NR 37 TC 23 Z9 23 U1 0 U2 9 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2006 VL 27 IS 3 BP 715 EP 721 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 028SF UT WOS:000236508400051 PM 16552023 ER PT J AU Espinoza, J Erez, O Romero, R AF Espinoza, J Erez, O Romero, R TI Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE preterm birth; infection; bacterial vaginosis ID PELVIC-INFLAMMATORY-DISEASE; PLASMA-CELL ENDOMETRITIS; INTRAUTERINE-CONTRACEPTIVE-DEVICES; ASYMPTOMATIC BACTERIAL VAGINOSIS; RANDOMIZED CONTROLLED-TRIAL; FEMALE REPRODUCTIVE-TRACT; CERVICAL-MUCUS PLUG; VAGINAL INFECTIONS; EARLY-PREGNANCY; IN-VITRO AB This article addresses the question of whether the uterine cavity is normally sterile and reviews the difficulties in conducting microbiologic studies of the endometrium, the limitations of conventional microbiologic techniques (cultivation-dependent), and the potential contribution of molecular microbiology to examine microbial diversity and burden of the endometrium. Issues pertaining to the diagnosis of chronic endometritis and the need for information about the prognostic value of this finding in subsequent pregnancies are discussed. The results of a randomized clinical trial of antibiotic administration versus placebo in women with a previous preterm birth are reviewed and commentary is provided. The emerging picture is that microbial-host interactions in the endometrial cavity are important for reproductive success. This is a US government work. There are no restrictions on its use. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48202 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 119 TC 46 Z9 53 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2006 VL 194 IS 3 BP 630 EP 637 DI 10.1016/j.ajog.2005.11.050 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 021LV UT WOS:000235985600007 PM 16522390 ER PT J AU Goldenberg, RL Mwatha, A Read, JS Adeniyi-Jones, S Sinkala, M Msmanga, G Martinson, F Hoffman, I Fawzi, W Valentine, M Emel, L Brown, E Mudenda, V Taha, TE AF Goldenberg, RL Mwatha, A Read, JS Adeniyi-Jones, S Sinkala, M Msmanga, G Martinson, F Hoffman, I Fawzi, W Valentine, M Emel, L Brown, E Mudenda, V Taha, TE CA HPTN024 Team TI The HPTN 024 Study: The efficacy of antibiotics to prevent chorioamnionitis and preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE antibiotics; preterm birth; chorioamnionitis; birth weight ID RANDOMIZED CONTROLLED-TRIAL; MATERNAL HIV-INFECTION; BACTERIAL VAGINOSIS; PREGNANT-WOMEN; METRONIDAZOLE TREATMENT; PREMATURE BIRTH; DELIVERY; LABOR; METAANALYSIS; CLINDAMYCIN AB Objective: The use of antibiotics to prevent preterm birth has achieved mixed results. Our goal in this study was to determine if antibiotics given prenatally and during labor reduce the incidence of preterm birth and histologic chorioamnionitis. Study design: A double-blind randomized placebo-controlled trial of antibiotics to reduce preterm birth was conducted in 4 African sites. Both HIV-infected and uninfected pregnant women were given 2 courses of antibiotics, prenatally at 24 weeks (metronidazole 250 mg and erythromycin 250 mg tid orally for 7 days), and during labor (metronidazole 250 mg and ampicillin 500 mg q 4 hours) or identically appearing placebos. Two thousand ninety-eight HIV-infected and 335 HIV-uninfected women had evaluable end points, including gestational age determined by both obstetric and pediatric criteria and birth weight (BWT). Pre- and post-treatment rates of various sexually transmitted infections (STI) were determined and placentas were evaluated for histologic chorioamnionitis. Results: Comparing antibiotic versus placebo treated HIV-infected and uninfected women, there were few differences in mean gestational age at delivery, the percent of preterm births, the time between randomization and delivery, or BWT. Four weeks after the 24-week antibiotic/placebo course, bacterial vaginosis, and trichomoniasis were reduced by 49% to 61% in the antibiotic groups compared with the placebo groups. However, in both the HIV-infected and uninfected groups, the placentas showed no difference in the rate of histologic chorioamnionitis. There were significant differences between HIV-infected and uninfected women, with the former having less education, a history of more stillbirths, more STIs, and in this pregnancy, a lower BWT (2949 vs 3100 g, P < .0001). Conclusion: Despite reducing the rate of vaginal infections, the antibiotic regimen used in this study did not reduce the rate of preterm birth, increase the time to delivery, or increase BWT. Failure of this regimen to reduce the rate of histologic chorioamnionitis may explain the reason the antibiotics failed to reduce preterm birth. (c) 2006 Mosby, Inc. All rights reserved. C1 Univ Alabama, Dept Obstet Gynecol, Birmingham, AL 35233 USA. FHCRC, SCHARP, Seattle, WA USA. NICHHD, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Minist Hlth, Lusaka, Zambia. Muhimbili Univ, Dept Community Hlth, Dar Es Salaam, Tanzania. Lilongwe Cent Hosp, Lilongwe, Malawi. Univ N Carolina, Ctr Infect Dis, Chapel Hill, NC 27515 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Family Hlth Int, Res Triangle Pk, NC 27709 USA. Univ Teaching Hosp, Dept Pathol, Lusaka, Zambia. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Goldenberg, RL (reprint author), Univ Alabama, Dept Obstet Gynecol, 1500 6th Ave S,CRWH 379, Birmingham, AL 35233 USA. EM rlg@uab.edu RI Brown, Elizabeth/A-8984-2008 FU NIAID NIH HHS [N01-AI-45200, N01-AI-35173, N01-AI-35173-117/412, U01-AI-47972, U01-AI-480006, U01-AI-48005] NR 30 TC 48 Z9 49 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2006 VL 194 IS 3 BP 650 EP 661 DI 10.1016/j.ajog.2006.01.004 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 021LV UT WOS:000235985600010 PM 16522393 ER PT J AU Toso, L Poggi, SH Roberson, R Woodard, J Park, J Abebe, D Spong, CY AF Toso, L Poggi, SH Roberson, R Woodard, J Park, J Abebe, D Spong, CY TI Prevention of alcohol-induced learning deficits in fetal alcohol syndrome mediated through NMDA and GABA receptors SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE fetal alcohol syndrome; alcohol; NMDA; GABA; learning; neurotrophic factors ID VASOACTIVE-INTESTINAL-PEPTIDE; DEPENDENT NEUROTROPHIC FACTOR; MOUSE MODEL; NEUROPROTECTION; PROTEIN; EXPOSURE; NEURONS; GROWTH; MICE; CREB AB Objective: Vasoactive intestinal peptide (VIP)-related peptides prevented the learning deficit in the offspring in a model for fetal alcohol syndrome. We evaluated whether the mechanism of the peptide protection included NR2B, NR2A, and GABA(A)alpha(5). Study design: Timed, pregnant C57BL6/J mice were injected on gestational day 8 with alcohol (0.03 mL/kg), placebo, or alcohol plus peptides. Embryos were harvested after 6 hours, 24 hours, and on gestational day 18. Some of the litters were allowed to deliver, and the adult brains harvested after the offspring were tested for learning. Calibrator-nornialized relative real-time polymerase chain reaction (PCR) was performed using primers for NR2B, NR2A, and GABAAa5 with GAPDH standardization. Statistic: analysis of variance (ANOVA) and Fisher PLSD, P < .05 was considered significant. Results: In the embryo, the peptides prevented NR2B rise (P < .001) at 6 hours, NR2B down-regulation (P = .002), and GABA(A)alpha(5) decrease (P < .01) on gestational day 18. In the adult, the peptides prevented NR2B down-regulation (P = .01) and NR2A up-regulation (P < .001). Conclusion: VIP-related peptides prevented alcohol-induced changes in NR2B, NR2A, and GABA(A)alpha(5). This may explain, at least in part, the peptides' prevention of alcohol-induced learning deficits. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHD, UPDN, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. INOVA Hosp, Dept Obstet & Gynecol, Alexandria, VA USA. RP Toso, L (reprint author), NICHD, UPDN, NIH, Bldg 9,Room 1W125,9 Memorial Dr MSC 0925, Bethesda, MD 20892 USA. EM laura_toso@hotmail.com FU Intramural NIH HHS NR 25 TC 12 Z9 12 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2006 VL 194 IS 3 BP 681 EP 686 DI 10.1016/j.ajog.2006.01.003 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 021LV UT WOS:000235985600014 PM 16522397 ER PT J AU Gomez, R Iams, JD Romero, R AF Gomez, R Iams, JD Romero, R TI A short cervix in women with preterm labor and intact membranes: A risk factor for microbial invasion of the amniotic cavity - Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter ID DELIVERY C1 Pontificia Univ Catolica Chile, Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Detroit, MI 48201 USA. RP Gomez, R (reprint author), Pontificia Univ Catolica Chile, Hosp Dr Sotero del Rio, CEDIP, Puente Alto, Chile. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2006 VL 194 IS 3 BP 902 EP 903 DI 10.1016/j.ajog.2005.07.030 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 021LV UT WOS:000235985600053 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG TI Rehabilitation medicine summit: Building research capacity: Executive summary SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article AB The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The five , (2) research culture, environ-elements of research capacity that guided the discussions were: (1) researchersment, and infrastructure; (3) funding; (4) partnerships-, and (5) metrics. The 100 participants included representives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. The small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multi-organizational initiative is called to pursue the agendas outlined in this report. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Boston Univ, Hlth & Disabil Res Inst, Boston, MA 02215 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Human Engn Res Labs, Pittsburgh, PA USA. Univ Florida, Coll Publ Hlth & Hlth Profess, Brooks Ctr, Gainesville, FL USA. Powers Pyles Sutter & Verville PC, Washington, DC USA. Univ Texas, Med Branch, Div Rehabil Sci, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM wfrontera@partners.org NR 3 TC 4 Z9 6 U1 0 U2 0 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD MAR-APR PY 2006 VL 60 IS 2 BP 165 EP 176 PG 12 WC Rehabilitation SC Rehabilitation GA 022VG UT WOS:000236083600006 PM 16596920 ER PT J AU Wong, TY Klein, R Islam, A Frances, M Folsom, AR Klein, BE Sharrett, AR Shea, S AF Wong, TY Klein, R Islam, A Frances, M Folsom, AR Klein, BE Sharrett, AR Shea, S CA Multi-Ethnic Study Athersclerosis TI Diabetic retinopathy in a multi-ethnic cohort in the United States SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID NON-HISPANIC WHITES; BLOOD-GLUCOSE CONTROL; RISK-FACTORS; MEXICAN-AMERICANS; GLYCOSYLATED HEMOGLOBIN; HARD EXUDATE; PREVALENCE; POPULATION; ADULTS; COMPLICATIONS AB PURPOSE: To describe the prevalence and risk factors of diabetic retinopathy in a multi,ethnic US population of whites, blacks, hispanics, and chinese. DESIGN: Cross-sectional study of 778 individuals from ages 45 to 85 years with diabetes, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: Retinal photographs were obtained with a 45 degrees nonmydriatic digital fundus camera. Presence and severity of diabetic retinopathy were graded at a central reading center on the basis of a modification of the Airlie House classification system. All participants underwent a standardized interview, examination, and laboratory investigations. RESULTS: In this population with diabetes, the prevalence of any retinopathy was 33.2% and macular edema 9.0%. The prevalence of any diabetic retinopathy and macular edema was significantly higher in blacks (36.7% and 11.1%) and hispanics (37.4% and 10.7%) than in whites (24.8% and 2.7%) and chinese (25.7% and 8.9%) (P =.01 and P =.007, comparing racial/ethnic differences for retinopathy and macular edema, respectively). Significant independent predictors of any retinopathy were longer duration of diabetes, higher fasting serum glucose, use of diabetic oral medication or insulin, and greater waist-hip ratio. Race was not an independent predictor of any retinopathy. CONCLUSIONs: This study provides contemporary data on the prevalence of and risk factors for diabetic retinopathy among whites, blacks, hispanics, and chinese participating in the MESA. C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Columbia Univ, Sch Med & Publ Hlth, Dept Med & Epidemiol, New York, NY USA. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [Z01 EY000403-06, Z01 EY000403-07, Z99 EY999999, ZIA EY000403-08]; NHLBI NIH HHS [N01 HC095159, HL 69979-03, N01 HC095160, N01 HC095161, N01 HC095162, N01 HC095163, N01 HC095164, N01 HC095165, N01 HC095169, N01HC95159, N01HC95165, N01HC95169, R01 HL069979, R01 HL069979-03] NR 40 TC 259 Z9 271 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2006 VL 141 IS 3 BP 446 EP 455 DI 10.1016/j.ajo.2005.08.063 PG 10 WC Ophthalmology SC Ophthalmology GA 022LS UT WOS:000236057900003 PM 16490489 ER PT J AU Nunemaker, CS Wasserman, DH McGuinness, OP Sweet, IR Teague, JC Satin, LS AF Nunemaker, CS Wasserman, DH McGuinness, OP Sweet, IR Teague, JC Satin, LS TI Insulin secretion in the conscious mouse is biphasic and pulsatile SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin; secretion; first phase; second phase; biphasic; mouse; in vivo; pulses; pulsatile ID PANCREATIC BETA-CELLS; PERFUSED RAT PANCREAS; SENSITIVE K+ CHANNELS; IN-VIVO; METABOLIC OSCILLATIONS; SIGNALING PATHWAYS; CALCIUM-CHANNELS; GLUCOSE INFUSION; ISLET CELLS; B-CELLS AB Islets in most species respond to increased glucose with biphasic insulin secretion, marked by a sharp first- phase peak and a slowly rising second phase. Mouse islets in vitro, however, lack a robust second phase. To date, this observation has not been extended in vivo. We thus compared insulin secretion from conscious mice with isolated mouse islets in vitro. The arterial plasma insulin response to a hyperglycemic clamp was measured in conscious mice 1 wk after surgical implantation of carotid artery and jugular vein catheters. Mice were transfused using clamps with blood from a donor mouse to maintain blood volume, allowing frequent arterial sampling. When plasma glucose in vivo was raised from similar to 5 to similar to 13 mM, insulin rose to a first-phase peak of 403 +/- 73% above basal secretion (n = 5), followed by a rising second phase of mean 289 +/- 41%. In contrast, perifused mouse islets (similar to 75 islets/ trial) responded with a similar first phase of 508 +/- 94% (n = 4) but a smaller and virtually flat second phase of 169 +/- 9% (n = 4, P < 0.05). Furthermore, the slope of the second-phase response differed significantly from zero in mice (2.63 +/- 0.39%/ min, P < 0.01), in contrast to perifused islets (0.18 +/- 0.14%/ min, P > 0.30). Mice also displayed pulsatile patterns in insulin concentration ( period: 4.2 +/- 0.4 min, n = 8). Conscious mice thus responded to increased glucose with biphasic and pulsatile insulin secretion, as in other species. The robust second phase observed in vivo suggests that the processes needed to generate second-phase insulin secretion may be abrogated by islet isolation. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN USA. Univ Washington, Dept Physiol, Seattle, WA USA. RP Satin, LS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus,PO Box 980524, Richmond, VA 23298 USA. EM lsatin@hsc.vcu.edu FU NIDDK NIH HHS [F32 DK-065462, F32 DK065462, R01 DK-46409, U24-DK-59637] NR 59 TC 35 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2006 VL 290 IS 3 BP E523 EP E529 DI 10.1152/ajpendo.00392.2005 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 010QU UT WOS:000235210000017 PM 16249252 ER PT J AU Theodorakis, MJ Carlson, O Michopoulos, S Doyle, ME Juhaszova, M Petraki, K Egan, JM AF Theodorakis, MJ Carlson, O Michopoulos, S Doyle, ME Juhaszova, M Petraki, K Egan, JM TI Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE duodenum; euglycemia; type 2 diabetes; glucagon-like peptide-1; gastric inhibitory polypeptide ID GLUCAGON-LIKE PEPTIDE-1; GASTRIC-INHIBITORY POLYPEPTIDE; DIABETES-MELLITUS; ENDOCRINE-CELLS; GASTROINTESTINAL-TRACT; INSULIN RELEASE; SMALL-INTESTINE; PLASMA-GLUCOSE; 7-36 AMIDE; SECRETION AB Among the products of enteroendocrine cells are the incretins glucagon-like peptide-1 (GLP-1, secreted by L cells) and glucose-dependent insulinotropic peptide (GIP, secreted by K cells). These are key modulators of insulin secretion, glucose homeostasis, and gastric emptying. Because of the rapid early rise of GLP-1 in plasma after oral glucose, we wished to definitively establish the absence or presence of L cells, as well as the relative distribution of the incretin cell types in human duodenum. We confirmed the presence of proglucagon and pro-GIP genes, their products, and glucosensory molecules by tissue immunohistochemistry and RT-PCR of laser-captured, single duodenal cells. We also assayed plasma glucose, incretin, and insulin levels in subjects with normal glucose tolerance and type 2 diabetes for 120 min after they ingested 75 g of glucose. Subjects with normal glucose tolerance (n = 14) had as many L cells (15 +/- 1), expressed per 1,000 gut epithelial cells, as K cells (13 +/- 1), with some containing both hormones (L/K cells, 5 +/- 1). In type 2 diabetes, the number of L and L/K cells was increased (26 +/- 2; P < 0.001 and 9 +/- 1; P < 0.001, respectively). Both L and K cells contained glucokinase and glucose transporter-1, -2, and -3. Newly diagnosed type 2 diabetic subjects had increased plasma GLP-1 levels between 20 and 80 min, concurrently with rising plasma insulin levels. Significant coexpression of the main incretin peptides occurs in human duodenum. L and K cells are present in equal numbers. New onset type 2 diabetes is associated with a shift to the L phenotype. C1 NIA, Diabet Sect, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. Univ Athens, Sch Med, Dept Clin Therapeut, Athens, Greece. Hippokrateion Hosp, Athens, Greece. RP Theodorakis, MJ (reprint author), NIA, Diabet Sect, Lab Clin Invest, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 62 TC 174 Z9 177 U1 1 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2006 VL 290 IS 3 BP E550 EP E559 DI 10.1152/ajpendo.00326.2004 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 010QU UT WOS:000235210000020 PM 16219666 ER PT J AU Exil, VJ Gardner, CD Rottman, JN Sims, H Bartelds, B Khuchua, Z Sindhal, R Ni, GM Strauss, AW AF Exil, VJ Gardner, CD Rottman, JN Sims, H Bartelds, B Khuchua, Z Sindhal, R Ni, GM Strauss, AW TI Abnormal mitochondrial bioenergetics and heart rate dysfunction in mice lacking very-long-chain acyl-CoA dehydrogenase SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE genetics; inborn errors; acyl-coenzyme A dehydrogenase; cardiomyopathy; hypothermia; hypoglycemia; bradycardia ID FATTY-ACID OXIDATION; TANDEM MASS-SPECTROMETRY; SUDDEN-DEATH; UNCOUPLING PROTEIN; DEFICIENT MICE; INBORN-ERRORS; OBESE; DISORDERS; DISEASE; CARDIOMYOPATHY AB Mitochondrial very-long-chain acyl-CoA dehydrogenase ( VLCAD) deficiency is associated with severe hypoglycemia, cardiac dysfunction, and sudden death in neonates and children. Sudden death is common, but the underlying mechanisms are not fully understood. We report on a mouse model of VLCAD deficiency with a phenotype induced by the stresses of fasting and cold, which includes hypoglycemia, hypothermia, and severe bradycardia. The administration of glucose did not rescue the mice under stress conditions, but rewarming alone consistently led to heart rate recovery. Brown adipose tissue (BAT) from the VLCAD(-/-) mice showed elevated levels of the uncoupling protein isoforms and peroxisome proliferator-activated receptor-alpha. Biochemical assessment of the VLCAD(-/-) mice BAT showed increased oxygen consumption, attributed to uncoupled respiration in the absence of stress. ADP-stimulated respiration was 23.05 (SD 4.17) and 68.24 (SD 6.3) nmol O-2 center dot min(-1) center dot mg mitochondrial protein(-1) for VLCAD(-/-) and VLCAD(-/-) mice, respectively (P < 0.001), and carbonyl cyanide p-trifluoromethoxyphenylhydrazone-stimulated respiration was 35.9 (SD 3.6) and 49.3 (SD 9) nmol O-2 center dot min(-1) center dot mg mitochondrial protein(-1) for VLCAD(-/-) and VLCAD(-/-) mice, respectively (P < 0.20), but these rates were insufficient to protect them in the cold. We conclude that disturbed mitochondrial bioenergetics in BAT is a critical contributing factor for the cold sensitivity in VLCAD deficiency. Our observations provide insights into the possible mechanisms of stress-induced death in human newborns with abnormal fat metabolism and elucidate targeting of specific substrates for particular metabolic needs. C1 Vanderbilt Univ, Sch Med, Dept Pediat, Div Cardiol, Nashville, TN 37212 USA. Washington Univ, Sch Med, St Louis, MO USA. Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Dept Internal Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA. RP Exil, VJ (reprint author), Vanderbilt Childrens Hosp, Div Pediat Cardiol, 2200 Childrens Way,Rm 5230 DOT, Nashville, TN 37232 USA. EM vernat.exil@vanderbilt.edu RI Khuchua, Zaza/J-6536-2016; OI Khuchua, Zaza/0000-0003-3582-5670; Exil, Vernat/0000-0001-5935-4039 NR 36 TC 28 Z9 29 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2006 VL 290 IS 3 BP H1289 EP H1297 DI 10.1152/ajpheart.00811.2005 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 010RI UT WOS:000235212400048 PM 16199475 ER PT J AU Allen, IC Hartney, JM Coffman, TM Penn, RB Wess, J Koller, BH AF Allen, IC Hartney, JM Coffman, TM Penn, RB Wess, J Koller, BH TI Thromboxane A(2) induces airway constriction through an M-3 muscarinic acetylcholine receptor-dependent mechanism SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE nerve; prostanoid; bronchoconstriction; asthma; vagus ID SMOOTH-MUSCLE-CELLS; OBSTRUCTIVE PULMONARY-DISEASE; PROSTANOID RECEPTORS; PHOSPHOLIPASE-C; HUMAN-PLATELETS; PROTEIN-KINASE; MICE LACKING; GUINEA-PIG; IN-VIVO; MOUSE AB Thromboxane A(2) (TXA(2)) is a potent lipid mediator released by platelets and inflammatory cells and is capable of inducing vasoconstriction and bronchoconstriction. In the airways, it has been postulated that TXA(2) causes airway constriction by direct activation of thromboxane prostanoid (TP) receptors on airway smooth muscle cells. Here we demonstrate that although TXA(2) can mediate a dramatic increase in airway smooth muscle constriction and lung resistance, this response is largely dependent on vagal innervation of the airways and is highly sensitive to muscarinic acetylcholine receptor (mAChR) antagonists. Further analyses employing pharmacological and genetic strategies demonstrate that TP-dependent changes in lung resistance and airway smooth muscle tension require expression of the M-3 mAChR subtype. These results raise the possibility that some of the beneficial actions of anticholinergic agents used in the treatment of asthma and chronic obstructive pulmonary disease result from limiting physiological changes mediated through the TP receptor. Furthermore, these findings demonstrate a unique pathway for TP regulation of homeostatic mechanisms in the airway and suggest a paradigm for the role of TXA(2) in other organ systems. C1 Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Wake Forest Univ, Hlth Sci Ctr, Ctr Human Genom, Winston Salem, NC 27109 USA. Duke Univ, Med Ctr, Div Nephrol, Durham, NC USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Koller, BH (reprint author), Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. EM Treawouns@aol.com FU NHLBI NIH HHS [HL-58506, HL-068141] NR 60 TC 22 Z9 22 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAR PY 2006 VL 290 IS 3 BP L526 EP L533 DI 10.1152/ajplung.00340.2005 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 010IX UT WOS:000235182700014 PM 16243899 ER PT J AU Paliege, A Parsumathy, A Mizel, D Yang, T Schnermann, J Bachmann, S AF Paliege, A Parsumathy, A Mizel, D Yang, T Schnermann, J Bachmann, S TI Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE tubulovascular signaling; reactive oxygen species ID NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; NADPH OXIDASE; UP-REGULATION; KIDNEY; LOCALIZATION; ANGIOTENSIN; METABOLISM; RELEASE; TEMPOL AB Paliege, A., A. Parsumathy, D. Mizel, T. Yang, J. Schnermann, and S. Bachmann. Effect of apocynin treatment on renal expression of Cox-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 290: R694-R700, 2006; doi:10.1152/ajpregu.00219.2005.-Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) synthesize type 1 nitric oxide synthase (NOS1) and type 2 cyclooxygenase (COX-2). Both nitric oxide (NO) and prostaglandins have been considered to mediate or modulate the control of renin secretion. Reactive oxygen species (ROS) produced locally by NADPH oxidase may influence NO bioavailability. We have tested the hypothesis that in hypertension elevated ROS levels may modify the expression of NOS1 and COX-2 in the JGA, thereby interacting with juxtaglomerular signaling. To this end, spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) received the specific NADPH oxidase inhibitor, apocynin, during 3 wk. Renal functional and histochemical parameters, plasma renin activity (PRA), and as a measure of ROS activity, urinary isoprostane excretion (IP) were evaluated. Compared with WKY, IP levels in untreated SHR were 2.2-fold increased, and NOS1 immunoreactiviy (IR) of JGA 1.5-fold increased, whereas COX-2 IR was reduced to 35%, renin IR to 51%, and PRA to 7%. Apocynin treatment reduced IP levels in SHR to 52%, NOS1 IR to 69%, and renin IR to 62% of untreated SHR, whereas renin mRNA, COX-2 IR, glomerular filtration rate, PRA, and systolic blood pressure remained unchanged. WKY revealed no changes under apocynin treatment. These data show that NADPH oxidase is an important contributor to elevated levels of ROS in hypertension. Upregulation of MD NOS1 in SHR may have the potential of blunting the functional impact of ROS at the level of bioavailable NO. Downregulated COX-2 and renin levels in SHR are apparently unrelated to oxidative stress, since apocynin treatment had no effect on these parameters. C1 Charite, Fac Med, Dept Vegetat Anat, Berlin, Germany. NIDDK, NIH, Bethesda, MD USA. Univ Utah, Vet Affairs Med Ctr, Salt Lake City, UT USA. RP Bachmann, S (reprint author), Univ Med Berlin, Charite, Inst Vegetat Anat, Campus Charite Mitte,Philippstr 12, D-10115 Berlin, Germany. EM sbachm@charite.de NR 37 TC 33 Z9 34 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 2006 VL 290 IS 3 BP R694 EP R700 DI 10.1152/ajpregu.00219.2005 PG 7 WC Physiology SC Physiology GA 010QX UT WOS:000235210300027 PM 16467505 ER PT J AU Kim, SW de Seigneux, S Sassen, MC Lee, J Kim, J Knepper, MA Frokiaer, J Nielsen, S AF Kim, SW de Seigneux, S Sassen, MC Lee, J Kim, J Knepper, MA Frokiaer, J Nielsen, S TI Increased apical targeting of renal ENaC subunits and decreased expression of 11 beta HSD2 in HgCl2-induced nephrotic syndrome in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE epithelial sodium channel; type 2 11 beta-hydroxysteroid dehydrogenase; collecting duct ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE-ACTIVITY; PUROMYCIN AMINONUCLEOSIDE; COLLECTING DUCT; MINERALOCORTICOID RECEPTOR; GLUCOCORTICOID RECEPTOR; BILE-ACIDS; KIDNEY; VASOPRESSIN; SODIUM; INHIBITION AB Nephrotic syndrome is often accompanied by sodium retention and generalized edema. We hypothesize that dysregulation of the epithelial sodium channel ( ENaC) and/or of sodium ( co) transporters may be responsible for the increased sodium retention associated with HgCl2-induced nephropathy. In addition, we examined the hypothesis that the expression of type 2 11 beta-hydroxysteroid dehydrogenase ( 11 beta HSD2) is reduced, contributing to the enhanced mineralocorticoid activity. Membranous nephropathy was induced in Brown Norway rats by repeated injections of HgCl2 ( 1 mg/kg sc), whereas the control group received only vehicle. After 13 days of treatment, the abundance of ENaC subunits, sodium ( co) transporters, and 11 beta HSD2 in the kidney was examined by immunoblotting and immunohistochemistry. HgCl2 treatment induced marked proteinuria, hypoalbuminemia,decreased urinary sodium excretion, and ascites. The protein abundance of alpha-ENaC was increased in the cortex/outer stripe of outer medulla ( OSOM) and inner stripe of the outer medulla ( ISOM). The protein abundances of beta-ENaC and gamma-ENaC were decreased in the cortex/OSOM while increased in the ISOM. Immunoperoxidase microscopy demonstrated increased targeting of ENaC subunits to the apical plasma membrane in the distal convoluted tubule, connecting tubule, and cortical and medullary collecting duct segments. Moreover, 11 beta HSD2 abundance was decreased in cortex/OSOM and ISOM. The protein abundances of type 3 Na/H exchanger ( NHE3), Na-K-2Cl cotransporter ( NKCC2), and thiazide-sensitive Na-Cl cotransporter ( NCC) were decreased. Moreover, the abundance of the alpha-1 subunit of the Na-K-ATPase was decreased in the cortex/OSOM and ISOM but remained unchanged in the inner medulla. These results suggest that increased apical targeting of ENaC subunits combined with diminished abundance of 11 beta HSD2 may contribute to sodium retention associated with HgCl2-induced nephrotic syndrome. The decreased abundance of NHE3, NKCC2, NCC, and Na-K-ATPase may play a compensatory role in promoting sodium excretion. C1 Univ Aarhus, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Chonnam Natl Univ, Sch Med, Res Inst Med Sci, Kwangju, South Korea. Univ Aarhus, Inst Anat, Aarhus C, Denmark. Catholic Univ, Dept Anat, Seoul, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Aarhus Univ Hosp, Inst Clin Med, Aarhus N, Denmark. RP Nielsen, S (reprint author), Univ Aarhus, 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 38 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2006 VL 290 IS 3 BP F674 EP F687 DI 10.1152/ajprenal.00084.2005 PG 14 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 009AE UT WOS:000235082700015 PM 16189294 ER PT J AU Volkow, ND AF Volkow, ND TI Stimulant medications: How to minimize their reinforcing effects? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID DOPAMINE; METHYLPHENIDATE; SYSTEM C1 NIDA, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 7 TC 40 Z9 42 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 359 EP 361 DI 10.1176/appi.ajp.163.3.359 PG 3 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000003 PM 16513852 ER PT J AU Rosenheck, R Leslie, D Keefe, R McEvoy, J Swartz, M Perkins, D Stroup, S Hsiao, JK Lieberman, J AF Rosenheck, R Leslie, D Keefe, R McEvoy, J Swartz, M Perkins, D Stroup, S Hsiao, JK Lieberman, J CA CATIE Study Investigators Grp TI Barriers to employment for people with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CLINICAL ANTIPSYCHOTIC TRIALS; EFFECTIVENESS CATIE PROJECT; SUPPORTED EMPLOYMENT; DISABILITY COMPENSATION; RATING-SCALE; DISORDERS; HALOPERIDOL; OLANZAPINE AB Objective: There is growing interest in identifying and surmounting barriers to employment for people with schizophrenia. The authors examined factors associated with participation in competitive employment or other vocational activities in a large group of patients with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, a multisite clinical trial comparing the effects of first- and second-generation antipsychotics. Method: Baseline data on more than 1,400 patients with a diagnosis of schizophrenia were collected before their entry into the CATIE study. Multinomial logistic regression was used to examine the relationship between participation in either competitive employment or other vocational activities and sociodemographic characteristics, schizophrenia symptoms, neurocognitive functioning, intrapsychic functioning, availability of psychosocial rehabilitation services, and local unemployment rates. Results: Altogether, 14.5% of the patients reported participating in competitive employment in the month before the baseline assessment, 12.6% reported other (noncompetitive) employment activity, and 72.9% reported no employment activity. Participation in either competitive or noncompetitive employment was associated with having less severe symptoms, better neurocognitive functioning, and higher scores on a measure of intrapsychic functioning that encompassed motivation, empathy, and other psychological characteristics. Competitive employment, in contrast to other employment or no employment, was negatively associated with receipt of disability payments as well as with being black. Greater access to rehabilitation services was associated with greater participation in both competitive and noncompetitive employment. Conclusions: Overall employment of persons with schizophrenia seems to be impeded by clinical problems, including symptoms of schizophrenia and poorer neurocognitive and intrapsychic functioning. However, participation in competitive employment may be specifically impeded by the potentially adverse incentives of disability payments and by race and may be promoted by the availability of rehabilitation services. C1 VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr 182, Dept Vet Affairs, West Haven, CT 06516 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Rosenheck, R (reprint author), VA Connecticut Hlth Care Syst, NE Program Evaluat Ctr 182, Dept Vet Affairs, 950 Campbell Ave, West Haven, CT 06516 USA. EM robert.rosenheck@yale.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 FU NIMH NIH HHS [N01 MH-90001] NR 28 TC 202 Z9 210 U1 2 U2 13 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 411 EP 417 DI 10.1176/appi.ajp.163.3.411 PG 7 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000013 PM 16513861 ER PT J AU Lencz, T Robinson, DG Xu, K Ekholm, J Sevy, S Gunduz-Bruce, H Woerner, MG Kane, JM Goldman, D Malhotra, AK AF Lencz, T Robinson, DG Xu, K Ekholm, J Sevy, S Gunduz-Bruce, H Woerner, MG Kane, JM Goldman, D Malhotra, AK TI DRD2 promoter region variation as a predictor of sustained response to antipsychotic medication in first-episode schizophrenia patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID D2 RECEPTOR GENE; POLYMORPHISMS; PHARMACOGENETICS AB Objective: All antipsychotics act on the dopamine D-2 receptor. The present study extends prior pharmacogenetic investigations of the D-2 receptor gene (DRD2) by examining, in first-episode schizophrenia patients, promoter region variation as a predictor of response time to two first-line atypical antipsychotics. Method: Patients experiencing their first episode of schizophrenia (N=61) were genotyped for two DRD2 promoter region polymorphisms (A-241G and -141C Ins/Del) and were randomly assigned to receive 16 weeks of treatment with either risperidone or olanzapine. Time until sustained response (two consecutive ratings without significant positive symptoms) for rare allele carriers versus wild types was examined by using Kaplan-Meier curves. Results: Relative to wild type homozygotes, G carriers (A-241G) exhibited a significantly faster time until response, whereas -141C Del carriers took a significantly longer time to respond. Diplotype analysis revealed similar results. Conclusions: These findings suggest that variation in the D2 receptor gene can, in part, explain variation in the timing of clinical response to antipsychotics in patients with first-episode schizophrenia. C1 Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY 11004 USA. Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Lencz, T (reprint author), Zucker Hillside Hosp, Dept Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM lencz@lij.edu RI Goldman, David/F-9772-2010; Lencz, Todd/J-3418-2014 OI Goldman, David/0000-0002-1724-5405; Lencz, Todd/0000-0001-8586-338X FU NIMH NIH HHS [K01 MH-65580, K32 MH-01760, P30 MH-60575, R01 MH-60004] NR 9 TC 84 Z9 91 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2006 VL 163 IS 3 BP 529 EP 531 DI 10.1176/appi.ajp.163.3.529 PG 3 WC Psychiatry SC Psychiatry GA 017XG UT WOS:000235726000029 PM 16513877 ER PT J AU Flegal, KM Williamson, DF Graubard, BL AF Flegal, KM Williamson, DF Graubard, BL TI Using adjusted relative risks to calculate attributable fractions SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID COMMON OUTCOMES; OBESITY; COHORT C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. Natl Canc Inst, Bethesda, MD USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4311, Hyattsville, MD 20782 USA. EM kmf2@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 9 TC 9 Z9 9 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2006 VL 96 IS 3 BP 398 EP 398 DI 10.2105/AJPH.2005.079731 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 017KA UT WOS:000235691300001 PM 16449574 ER PT J AU Trochim, WM Cabrera, DA Milstein, B Gallagher, RS Leischow, SJ AF Trochim, WM Cabrera, DA Milstein, B Gallagher, RS Leischow, SJ TI Practical challenges of systems thinking and modeling in public health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Review ID ORGAN DYSFUNCTION SYNDROME; COMPLEXITY SCIENCE; CHAOS THEORY; DYNAMICS; MORTALITY; DISEASE; VARIABILITY; MANAGEMENT; PREDICTOR; FRACTALS AB Objectives. Awareness of and support for systems thinking-and modeling in the public health field are growing, yet there are many practical challenges to implementation. We sought to identify and describe these challenges from the perspectives of practicing public health professionals. Methods. A systems-based methodology, concept mapping, was used in a study of 133 participants from 2 systems-based public health initiatives (the Initiative for the Study and Implementation of Systems and the Syndemics Prevention Network). This method identified 100 key challenges to implementation of systems thinking and modeling in public health work. Results. The project resulted in a map identifying 8 categories of challenges and the dynamic interactions among them. Conclusions. Implementation by public health professionals of the 8 simple rules we derived from the clusters in the map identified here will help to address challenges and improve the organization of systems that protect the public's health. C1 Cornell Univ, Dept Policy Anal & Management, Ithaca, NY 14853 USA. Cornell Univ, Dept Educ, Ithaca, NY 14853 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Gallagher & Assoc, Ithaca, NY USA. NCI, Bethesda, MD 20892 USA. RP Trochim, WM (reprint author), Cornell Univ, Dept Policy Anal & Management, 249 MVR Hall, Ithaca, NY 14853 USA. EM wmt1@cornell.edu RI Trochim, William/A-1250-2007 OI Trochim, William/0000-0003-0369-2922 NR 126 TC 107 Z9 108 U1 1 U2 25 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2006 VL 96 IS 3 BP 538 EP 546 DI 10.2105/AJPH.2005.066001 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 017KA UT WOS:000235691300028 PM 16449581 ER PT J AU Butler, LM London, SJ Yu, MC Tseng, M Koh, WP Lee, HP AF Butler, LM London, SJ Yu, MC Tseng, M Koh, WP Lee, HP TI On the usage of principal components analysis and multiple testing SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 Univ Calif Davis, Davis, CA 95616 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Minnesota, Minneapolis, MN USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Natl Univ Singapore, Singapore 117548, Singapore. RP Butler, LM (reprint author), Univ Calif Davis, Davis, CA 95616 USA. RI Tseng, Marilyn/B-9334-2016 OI Tseng, Marilyn/0000-0002-9969-9055 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2006 VL 173 IS 5 BP 574 EP 575 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 016KK UT WOS:000235618900018 ER PT J AU Bolanowski, A Mannon, RB Holland, SM Malech, HL Aschan, J Palmblad, J Hale, DA Kirk, AD AF Bolanowski, A Mannon, RB Holland, SM Malech, HL Aschan, J Palmblad, J Hale, DA Kirk, AD TI Successful renal transplantation in patients with chronic granulomatous disease SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE chronic granulomatous disease; kidney; transplant ID BONE-MARROW-TRANSPLANTATION; INFECTIONS AB Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population, and is often attributed to the necessary use of nephrotoxic anti-infectives. In this report, we present the experiences of two centers in transplantation of three patients with CGD: one transplanted with CGD, one cured of his CGD with bone marrow transplantation who subsequently underwent kidney transplantation and one that received a kidney transplant prior to being cured of CGD via a sequential peripheral blood stem cell transplant (SCT). All three recipients have enjoyed excellent outcomes. Their courses demonstrate the absolute requirements for a multidisciplinary and compulsive approach before, during and after transplantation. These case reports also highlight the unexpectedly benign effects of immunosuppressive therapy in this patient population. C1 NIAID, Natl Naval Med Ctr, Dept Surg, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Transplantat Branch, Natl Inst Diabet Digest & Kidney Dis, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD USA. Natl Inst Allergy & Infect Dis, Lab Clin Infect Dis, Bethesda, MD USA. Natl Inst Allergy & Infect Dis, Lab Host Def, Bethesda, MD USA. Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden. RP Kirk, AD (reprint author), NIAID, Natl Naval Med Ctr, Dept Surg, Bethesda, MD 20892 USA. EM AllanK@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012; OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS NR 13 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2006 VL 6 IS 3 BP 636 EP 639 DI 10.1111/j.1600-6143.2006.01232.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 010UU UT WOS:000235224200027 PM 16468977 ER PT J AU McPherson, T Fay, MP Singh, S Penzer, R Hay, R AF McPherson, T Fay, MP Singh, S Penzer, R Hay, R TI Health workers' agreement in clinical description of filarial lymphedema SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID BANCROFTIAN FILARIASIS; ACUTE ADENOLYMPHANGITIS; LYMPHATIC FILARIASIS; BRUGIAN FILARIASIS; FOOT INFECTION; ACUTE ATTACKS; COEFFICIENTS; ASSOCIATION; EFFICACY; LESIONS AB Severity of lymphedema and presence of entry lesions are risk factors for acute bacterial dermatolymphangioadenitis (ADLA) in those with filarial lymphedema. Recurrent ADLA causes acute morbidity and progression of lymphedema severity; however, there is little work assessing the ability of health workers to reliably stage disease severity and identify risk entry lesions. This knowledge is important in initiation of management and assessing interventions. We evaluated inter-rater reliability with two independent health workers rating both legs of 17 patients using a questionnaire and the Dreyer classification of lymphedema. The health workers could reliably stage lymphedema with high agreement (RMAC weighted kappa of 0.89) and identify nail, interdigital, and other skin lesions. However, there was less consistency in identifying the clinical nature of skin lesions. This indicates that the Dreyer classification can be a replicable way to stage lymphedema and a questionnaire can deliver high observer agreement on the presence of risk lesions. C1 NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. WHO, Pan Amer Hlth Org, Georgetown, Guyana. Minist Hlth, Georgetown, Guyana. Univ Southampton, Sch Nursing & Midwifery, Southampton SO9 5NH, Hants, England. Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland. RP Fay, MP (reprint author), NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. EM tessmcp@hotmail.com; mfay@niaid.nih.gov; rpenzer@opalskin.co.uk RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS NR 30 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2006 VL 74 IS 3 BP 500 EP 504 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 020PY UT WOS:000235923300025 PM 16525113 ER PT J AU Xu, X Roman, JM Veenstra, TD Van Anda, J Ziegler, RG Issaq, HJ AF Xu, X Roman, JM Veenstra, TD Van Anda, J Ziegler, RG Issaq, HJ TI Analysis of fifteen estrogen metabolites using packed column supercritical fluid chromatography-mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN-URINE; ASSAY AB Packed column supercritical fluid chromatography with tandem mass spectrometry was used for the separation of estrone, estradiol, estriol, 16-epiestriol, 17-epiestriol, 16-ketoestradiol, 16 alpha-hydroxyestrone, 2-methoxyestrone, 4-methoxyestrorre, 2-hydroxyestrone-3-methyl ether, 2-methoxyestradiol, 4-methoxyestradiol, 2-hydroxyestrone, 4-hydroxyestrone, and 2-hydroxyestradiol. A gradient of methanol in carbon dioxide (0-30% methanol in 15 min, 2% change/min) at a flow rate of 2 mL/min and cyanopropyl silica column connected in series with a diol column, both 2.1 mm i.d. x 150 mm long, packed with 5-mu m spherical silica-based particles, resulted in the separation and quantification of all 15 estrogens in less than 10 min. The limit of detection (LOD) and limit of quantitation (LOQ) of this pSFC MS/MS method was determined to be 0.5 (S/N = 3), and 5 pg, respectively. Compared with RP-HPLC MS analysis of the same mixture in terms of speed of analysis and sensitivity, pSFC MS is much faster, 10 versus 70 min, with comparable LOD and LOQ. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. Mettler Toledo, Newark, DE 19702 USA. NCI, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. RP Issaq, HJ (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. EM issaqh@ncifcrf.go FU NCI NIH HHS [N01-CO-12400] NR 11 TC 44 Z9 44 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 1 PY 2006 VL 78 IS 5 BP 1553 EP 1558 DI 10.1021/ac051425c PG 6 WC Chemistry, Analytical SC Chemistry GA 020PJ UT WOS:000235921700031 PM 16503607 ER PT J AU Kurup, K Chan, CC AF Kurup, K Chan, CC TI Mycobacterium-related ocular inflammatory disease: Diagnosis and management SO ANNALS ACADEMY OF MEDICINE SINGAPORE LA English DT Article DE anti-TB therapy; granuloma; ocular infection; PPD test; tuberculosis ID LATENT TUBERCULOSIS INFECTION; EYE; CHORIORETINITIS; BOVIS; ASSAY AB Introduction: Worldwide, there are approximately 8 million new cases and 3 million deaths from tuberculosis (TB) each year. TB affects the entire body and the eye. Although ocular TB is considered rare, its incidence has varied widely across time, patient populations, and geography. We report 2 patients with unique presentations of ocular TB and detail the treatment and outcome of the disease. Materials and Methods: Two cases of ocular inflammation, one with a medical history of systemic TB and the other, with that of presumed systemic TB, were examined. Choroidal granuloma developed in one, and scleritis developed in the other. The literature on ocular TB was comprehensively reviewed. Results: Both patients were diagnosed with ocular TB. The histology of the systemic TB lesions was also illustrated. They responded to aggressive anti-TB and anti-inflammatory therapies. Conclusions: The diagnosis and management of ocular TB can pose a significant challenge. Physicians and ophthalmologists must include TB among the differential diagnoses of patients with ocular inflammatory diseases and treat ocular TB with a combination of anti-TB and immunosuppressive medications as needed. Immunosuppressive medications applied in this setting must be cautioned and only prescribed by ophthalmologists who are familiar with these agents. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 48 TC 2 Z9 2 U1 1 U2 2 PU ACAD MEDICINE SINGAPORE PI REPUBLIC SINGAPORE PA 142 NEIL RD, REPUBLIC SINGAPORE 088871, SINGAPORE SN 0304-4602 J9 ANN ACAD MED SINGAP JI Ann. Acad. Med. Singap. PD MAR PY 2006 VL 35 IS 3 BP 203 EP 209 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 047SP UT WOS:000237899300012 ER PT J AU Nduka, FO Etusim, PE Nwaugo, VO Oguariri, RM AF Nduka, FO Etusim, PE Nwaugo, VO Oguariri, RM TI The effects of quarry mining on the epidemiology of Schistosoma haematobium in schoolchildren, in Ishiagu, south-eastern Nigeria SO ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY LA English DT Article ID SUB-SAHARAN AFRICA; INFECTION; MORBIDITY; PATTERNS AB Over the last two decades there has been a noticeable increase in the activities of quarry-mining companies in the Ishiagu area of south-eastern Nigeria. These activities have produced an ever-growing number of abandoned quarry pits that usually quickly fill with water and appear to become suitable habitats for the freshwater snails that may act as intermediate hosts of Schistosoma haematobium. To examine the potential role of quarry mining on the prevalence of urinary schistosomiasis caused by S. haematobium, urine samples were collected from 1819 schoolchildren in northern Ishiagu (an area with intense mining activities and many quarry pits) and from 252 schoolchildren in southern Ishiagu (an area with no mining activity or quarry pits). When these 2071 samples were checked for schistosome eggs, 1005 (48.5%) were found positive and 252 (25.1%) of the infected children showed visible haematuria. The children from northern Ishiagu were much more likely to be infected than the children from the south (53.3% v. 13.9%; P < 0.001). Curiously, only the children from northern Ishiagu showed a gender-related difference in prevalence that was statistically significant, with boys more likely to be infected than girls (60.9% v. 38.5%; P < 0.001). Although the 'children' investigated varied in age from 5 to 20 years, no statistically significant increase or decrease in prevalence with age was apparent. Four species of snails (Bulinus globosus, B. rohlfsi, B. forskalii and B. senegalensis) were found in the overall study area but B. globosus was only found in the quarry pits in northern Ishiagu and never in the water bodies of southern Ishiagu. It does appear that quarry-mining activity in the Ishiagu area is a factor in the local epidemiology of urinary schistosomiasis, with the water bodies that form in the abandoned quarry pits serving as the principal foci of transmission. C1 Sci Applicat Int Corp, NIAID, NIH, NCI, Frederick, MD 21702 USA. Abia State Univ, Sch Biol Sci, Dept Zool, Uturu, Abia State, Nigeria. RP Oguariri, RM (reprint author), Sci Applicat Int Corp, NIAID, NIH, NCI, Bldg 550,Room 104, Frederick, MD 21702 USA. EM oguaririr@niaid.nih.gov NR 29 TC 3 Z9 3 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0003-4983 J9 ANN TROP MED PARASIT JI Ann. Trop. Med. Parasitol. PD MAR PY 2006 VL 100 IS 2 BP 155 EP 161 DI 10.1179/136485906x78544 PG 7 WC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine SC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine GA 022CB UT WOS:000236031200007 PM 16492363 ER PT J AU Cole, GW Alleva, AFM Zuo, JT Sehgal, SS Yeow, WS Schrump, DS Nguyen, DM AF Cole, GW Alleva, AFM Zuo, JT Sehgal, SS Yeow, WS Schrump, DS Nguyen, DM TI Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126 SO ANTICANCER RESEARCH LA English DT Article DE EGFR; MAPK; MEK; ERK1/2; PI3K inhibitor LY294002; MEK inhibitor UO126; apoptosis; angiogenesis; prometastasis phenotypes; motility ID EPIDERMAL-GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; SMALL-CELL LUNG; SIGNAL-REGULATED KINASE; FACTOR-MEDIATED INTERACTION; BREAST-CANCER CELLS; FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; K-RAS AB Background: This study aimed to evaluate the impact of selective abrogation of either the MEK/ERK1/2 (U0126 or PD98059) or the PI3K/AKT (LY294002) signaling cascade on cell proliferation, motility and invasion and production of VEGF (collectively termed pro-metastasis phenotypes) in cultured malignant pleural mesothelioma (MPM) cells. Materials and Methods: Treatment-induced cytotoxicity was evaluated by MTT or Annexin V assays. Cell motility was assessed by wound healing and Matrigel invasion assays. VEGF in conditioned media of cancer cells was measured by ELISA. Results: LY294002 and U0126 significantly inhibited cell proliferation and clonogenicity of MPM cells in vitro. A substantial reduction of cell motility, Matrigel invasion as well as inhibition of basal or EGF-induced VEGF-production were observed in drug-treated cells. Conclusion: The selective MEK or PI3K kinase inhibitors are equally effective in down-regulating the expression of prometastasis phenotypes, suggesting that MEK or PI3K are appropriate targets for the development of molecular therapeutics for malignant pleural mesothelioma. C1 NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), Clin Res Ctr, Room 4W-4-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM Dao_Nguyen@nih.gov FU Intramural NIH HHS NR 83 TC 20 Z9 20 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2006 VL 26 IS 2A BP 809 EP 821 PG 13 WC Oncology SC Oncology GA 030ZV UT WOS:000236674800001 PM 16619474 ER PT J AU Chiu, SJ Marcucci, G Lee, RJ AF Chiu, SJ Marcucci, G Lee, RJ TI Efficient delivery of an antisense oligodeoxyribonucleotide formulated in folate receptor-targeted liposomes SO ANTICANCER RESEARCH LA English DT Article DE antisense oligodeoxyribonucleotide; folate receptor; liposomes; Bcl2; drug targeting; leukemia; G3139; antisense delivery ID STERICALLY STABILIZED LIPOSOMES; MODIFIED ADENOVIRAL VECTORS; NONVIRAL GENE DELIVERY; IN-VITRO; GRAFT-POLYETHYLENIMINE; INTRACELLULAR DELIVERY; MEDIATED TRANSFECTION; LUNG-CANCER; TUMOR-CELLS; THERAPY AB Background: Folate receptors (FRs) are cellular surface markers for numerous solid tumors and myeloid leukemias. The aim of this study was to develop an antisense oligodeoxyribonucleotide (ODN) carrier targeting FR-overexpressing cancer cells using folate (FA) as the targeting moiety. G3139, a phosphorothioate antisense ODN against human bcl2 mRNA, was evaluated in this study. Materials and Methods: G3139-containing liposomes were prepared using an ethanol dilution method For the targeted formulation, 0.5 mol% of folate-PEG-DSPE was incorporated as a targeting ligand into cationic liposomes composed of DC-Chol/egg PC/PEG-DSPE at 25:65:10 mol/mol. Particle size and surface charge were measured and cellular uptake was assessed by fluorescence microscopy and flow cytometry. The ODN-containing formulations were evaluated in FR + KB cells for Bcl2 down-regulation measured by Western blot. The cytotoxicity of the formulations was determined by MTT assay. Results: The G3139-containing liposomes had an average diameter of 80-90 nm with high ODN entrapment efficiency (70-80%). Incorporation of the folate ligand did not significantly alter the particle size and entrapment efficiency. The formulation exhibited colloidal stability in a serum-containing environment. In uptake studies, the folate-targeted formulation showed ligand concentration-dependent uptake that was up to 6-fold more efficient than that of the non-targeted formulation (p < 0.05). The uptake could be blocked by an excess amount of free folate, thus indicating an FR-dependent mechanism. Conclusion: FR-targeted G3139-containing liposomes showed promising transfection activity in KB cells. FR-targeted formulations were capable of specific targeting to FR-overexpressing cell lines and optimizing the amount of folate ligand in the liposomal formulation can result in more efficient antisense delivery. C1 Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. Ohio State Univ, NSF, NSEC, Columbus, OH 43210 USA. Ohio State Univ, NCI, CCC, Columbus, OH 43210 USA. Ohio State Univ, Div Human Canc Genet, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Div Hematol & Oncol, Dept Internal Med, Columbus, OH 43210 USA. RP Lee, RJ (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, 500 W 12th Ave,LM Parks Hall, Columbus, OH 43210 USA. EM lee.1339@osu.edu FU NCI NIH HHS [R01 CA095673, P30CA16058] NR 47 TC 22 Z9 24 U1 0 U2 5 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2006 VL 26 IS 2A BP 1049 EP 1056 PG 8 WC Oncology SC Oncology GA 030ZV UT WOS:000236674800032 PM 16619505 ER PT J AU Dotis, J Simitsopoulou, M Dalakiouridou, M Konstantinou, T Taparkou, A Kanakoudi-Tsakalidou, F Walsh, TJ Roilides, E AF Dotis, J Simitsopoulou, M Dalakiouridou, M Konstantinou, T Taparkou, A Kanakoudi-Tsakalidou, F Walsh, TJ Roilides, E TI Effects of lipid formulations of amphotericin B on activity of human monocytes against Aspergillus fumigatus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN NEUTROPHILS; NITRIC-OXIDE; ANTIFUNGAL THERAPY; RESPIRATORY BURST; SUPEROXIDE ANION; EXPRESSION; INVITRO; UPDATE; AGENTS AB The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex, and amphotericin B colloidal dispersion (ABCD) on antifungal activity of human monocytes (MNCs), an important component of antifungal host defense, against Aspergillus fumigatus were compared to those of deoxycholate amphotericin B (DAMB). MNCs from healthy volunteers were incubated with 1 or 5 mu g/ml DAMB and 5 or 25 mu g/ml lipid formulations for 22 h. Drug-pretreated or untreated MNCs were then washed and assayed for the following: (i) activity against A. fumigatus hyphae by XTT assay at MNC:hypha ratios of 10:1 and 20:1; (ii) production of superoxide anion (O-2(-)) from MNCs in response to hyphae by cytochrome c reduction; (iii) production of hydrogen peroxide (H2O2) and H2O2-dependent intracellular intermediates (DIIs), such as OH- and HOCl, from MNCs in response to A. fumigatus culture supernatant by flow cytometric measurement of dihydrorhodamine-1,2,3 oxidation. With the exception of 1 mu g/ml DAMB and 5 mu g/ml LAMB or ABCD at 10:1, all amphotericin B formulations at both concentrations and MNC:hypha ratios enhanced MNC-induced damage of A. fumigatus hyphae compared to results with untreated cells (P < 0.01). While MNC O-2(-) production upon hyphal challenge, an early event in oxidative burst, was not affected by the drugs, production of H2O2 and DIIs, late events, were significantly increased by all four drugs (P < 0.01). At clinically relevant concentrations, both conventional amphotericin B and its lipid formulations enhance antihyphal activity of MNCs against A. fumigatus in association with significant augmentation of H2O2 and DIIs but not O-2(-), further demonstrating the immunomodulatory antifungal activities of these agents. C1 Aristotle Univ Thessaloniki, Dept Pediat 3, Hippokration Hosp, Infect Dis Lab, GR-54642 Thessaloniki, Greece. Aristotle Univ Thessaloniki, Dept Pediat 1, Hippokration Hosp, Clin Immunol Lab, GR-54642 Thessaloniki, Greece. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Dept Pediat 3, Hippokration Hosp, Infect Dis Lab, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr NR 26 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2006 VL 50 IS 3 BP 868 EP 873 DI 10.1128/AAC.50.3.868-873.2006 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 018SY UT WOS:000235786300006 PM 16495244 ER PT J AU Kocisko, DA Vaillant, A Lee, KS Arnold, KM Bertholet, N Race, RE Olsen, EA Juteau, JM Caughey, B AF Kocisko, DA Vaillant, A Lee, KS Arnold, KM Bertholet, N Race, RE Olsen, EA Juteau, JM Caughey, B TI Potent antiscrapie activities of degenerate phosphorothioate oligonucleotides SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RESISTANT PRION PROTEIN; CONTINUOUS INTRAVENOUS-INFUSION; DEXTRAN SULFATE 500; PHASE-I TRIAL; NUCLEOCAPSID PROTEIN; INCUBATION PERIOD; ADVANCED CANCER; CULTURED-CELLS; CONGO RED; SCRAPIE AB Although transmissible spongiform encephalopathies (TSEs) are incurable, a key therapeutic approach is prevention of conversion of the normal, protease-sensitive form of prion protein (PrP-sen) to the disease-specific protease-resistant form of prion protein (PrP-res). Here degenerate phosphorothioate oligonucleotides (PS-ONs) are introduced as low-nM PrP-res conversion inhibitors with strong antiscrapie activities in vivo. Comparisons of various PS-ON analogs indicated that hydrophobicity and size were important, while base composition was only minimally influential. PS-ONs bound avidly to PrP-sen but could be displaced by sulfated glycan PrP-res inhibitors, indicating the presence of overlapping binding sites. Labeled PS-ONs also bound to PrP-sen on live cells and were internalized. This binding likely accounts for the antiscrapie activity. Prophylactic PS-ON treatments more than tripled scrapie survival periods in mice. Survival times also increased when PS-ONs were mixed with scrapie brain inoculum. With these antiscrapie activities and their much lower anticoagulant activities than that of pentosan polysulfate, degenerate PS-ONs are attractive new compounds for the treatment of TSEs. C1 REPLICor Inc, Laval, PQ H7V 5B7, Canada. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Juteau, JM (reprint author), REPLICor Inc, Laval, PQ H7V 5B7, Canada. EM jmjuteau@replicor.com; bcaughey@niaid.nih.gov RI Lee, Kil/D-3678-2012 FU Intramural NIH HHS NR 43 TC 64 Z9 68 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2006 VL 50 IS 3 BP 1034 EP 1044 DI 10.1128/AAC.50.3.1034-1044.2006 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 018SY UT WOS:000235786300028 PM 16495266 ER PT J AU Strehl, U Trevorrow, T Veit, R Hinterberger, T Kotchoubey, B Erb, M Birbaumer, N AF Strehl, U Trevorrow, T Veit, R Hinterberger, T Kotchoubey, B Erb, M Birbaumer, N TI Deactivation of brain areas during self-regulation of slow cortical potentials in seizure patients SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Article DE epilepsy; functional magnetic resonance imaging; neurofeedback; slow cortical potentials; self-regulation ID EPILEPSY; FMRI; HUMANS AB This study investigates the neurophysiological basis of EEG feedback for patients with epilepsy. Brain areas are identified that become hemodynamically deactivated when epilepsy patients, trained in EEG self-regulation, generate positive slow cortical potentials (SCPs). Five patients were trained in producing positive SCPs, using a training protocol previously established to reduce seizure frequency in patients with drug refractory epilepsy. Patients attempted to produce positive SCP shifts in a functional magnetic resonance imaging (fMRI) scanner. Two patients were able to reliably produce positive SCP shifts. When these successful regulators were prompted to produce positive SCPs, blood oxygen level-dependent (BOLD) response indicated deactivation, in comparison to a control state, around the recording electrode, frontal lobe, and thalamus. Unsuccessful regulators' BOLD response indicated no deactivation in cortical areas proximal to the active electrode. No thalamic deactivation was found in poor regulators. Decreased seizure frequency from SCP training may be the result of positively reinforced inhibition in cortical areas proximal to active electrode placement, the frontal cortex, and the thalamus. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Chaminade Univ, Dept Psychol, Honolulu, HI USA. Univ Tubingen, Dept Neuroradiol, CNS, Sect Expt Magnet Resonance, D-72074 Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Strehl, U (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM ute.strehl@uni-tuebingen.de RI Veit, Ralf/F-8907-2012; OI Veit, Ralf/0000-0001-9860-642X; Erb, Michael/0000-0002-9311-4693 NR 21 TC 17 Z9 18 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-0586 J9 APPL PSYCHOPHYS BIOF JI Appl. Psychophysiol. Biofeedback PD MAR PY 2006 VL 31 IS 1 BP 85 EP 94 DI 10.1007/s10484-006-9006-6 PG 10 WC Psychology, Clinical SC Psychology GA 049PB UT WOS:000238027400007 PM 16752105 ER PT J AU Allen, RH Mage, DT Gondy, G Kodali, A Christensen, C Coble, J Stewart, P AF Allen, Ruth H. Mage, David T. Gondy, Gauthami Kodali, Anuradha Christensen, Carol Coble, Joseph Stewart, Patricia TI Investigation of job-related pesticide exposure in the Third National Health and Nutrition Examination Survey SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Article DE creatinine; exposure; job exposure matrix; occupation; priority toxicant reference range study; risk assessment; urinary pesticides analytes ID CREATININE AB The Third National Health and Nutrition Examination Survey gathered health and job data from a sample of the US population. Researchers collected urine samples from a subset of subjects and analyzed it for 12 pesticide residues or metabolites tie, analytes). They investigated the relationship between the industries and jobs reported and the analytes detected in the urine samples. The authors found an association between several jobs and the concentration for one or more pesticide analytes above the 90th percentile. They applied a job exposure matrix to categorize subjects on their potential for job exposures to pesticides. For the detected analytes, the subjects with the highest potential for occupational exposures to insecticides were more likely to have an analyte concentration above the 90th percentile and to have an average analyte concentration score 30% higher than that of subjects reporting jobs with the lowest exposure potential. These findings indicate that occupational exposure may not be a major source of pesticide exposure among the general population. C1 US EPA, Washington, DC 20460 USA. Temple Univ, Dept Publ Hlth, Philadelphia, PA 19122 USA. Temple Univ, Inst Survey Res, Philadelphia, PA 19122 USA. NCI, NIH, Rockville, MD USA. RP Allen, RH (reprint author), US EPA, Washington, DC 20460 USA. EM allen.ruth@epa.gov FU Intramural NIH HHS NR 17 TC 3 Z9 3 U1 0 U2 2 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PD MAR-APR PY 2006 VL 61 IS 2 BP 75 EP 86 DI 10.3200/AEOH.61.2.75-86 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 186VT UT WOS:000247807200005 PM 17649959 ER PT J AU Compton, CC AF Compton, CC TI Key issues in reporting common cancer specimens - Problems in pathologic staging of common cancer SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2005 CL San Antonio, TX SP US & Canadian Acad Pathol ID LYMPH-NODE METASTASES; DISEASE-FREE SURVIVAL; LARGE BOWEL-CANCER; COLORECTAL-CANCER; COLON-CANCER; MULTIVARIATE-ANALYSIS; PROGNOSTIC-FACTORS; LOCAL RECURRENCE; MINIMUM NUMBER; RECTAL-CANCER AB Con text.-Standardized pathologic assessment is a quality measure for cancer care. Objective.-Pathologic staging parameters and the clinically important stage-independent pathologic factors that pathologists find most problematic to evaluate in colorectal cancer resection specimens are reviewed. The objective of this review is to provide practical guidance for the practicing surgical pathologist. Data Sources.-Published literature related to the TNM staging system for colorectal cancer of the American Joint Committee on Cancer and the International Union Against Cancer and to stage-independent tissue-based prognostic factor evaluation was included in the review. Study Selection, Data Extraction, and Synthesis.-Published guidelines from authoritative sources and published peer-reviewed data related to colorectal cancer staging and pathologic prognostic factor assessment were included for consideration. The general and site-specific rules of application of the American joint Committee on Cancer and international Union Against Cancer TNM staging system for the colorectum and the protocol for evaluation of colorectal cancer resection specimens of the Cancer Committee of the College of American Pathologists served as the basis for discussion and amplified with practical advice on specific application. Conclusions.-Standardization of pathologic evaluation of colorectal cancer resection specimens is essential for optimal patient care and is aided by the use of data-driven guidelines that are easily understood and consistently applied. C1 Natl Canc Inst, Off Biorepositories & Bioscpecimen Res, Bethesda, MD 20892 USA. McGill Univ, Dept Pathol, Ctr Hlth, Montreal, PQ, Canada. RP Compton, CC (reprint author), Natl Canc Inst, Off Biorepositories & Bioscpecimen Res, 31 Ctr Dr,Bldg 31,Suite 10A03, Bethesda, MD 20892 USA. EM comptcar@mail.nih.gov NR 36 TC 49 Z9 50 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2006 VL 130 IS 3 BP 318 EP 324 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 022JV UT WOS:000236052800005 PM 16519558 ER PT J AU Wu, CW Seo, HJ Cohen, LG AF Wu, CW Seo, HJ Cohen, LG TI Influence of electric somatosensory stimulation on paretic-hand function in chronic stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE electric stimulation; neuronal plasticity; rehabilitation ID HUMAN MOTOR CORTEX; PAIRED ASSOCIATIVE STIMULATION; PERIPHERAL-NERVE STIMULATION; SENSORY STIMULATION; DIGIT STIMULATION; PARIETAL CORTEX; BRAIN INJURY; SPINAL-CORD; MODULATION; EXCITABILITY AB Objective: To test the influence of electric somatosensory stimulation on performance of the Jebsen-Taylor Hand Function Test (JTHFT), a widely used assessment of functional hand motor skills, by the paretic arm in patients with chronic stroke. Design: Initially, patients trained for several sessions until reaching plateau performance on the JTHFT. Subsequently, they entered a crossover randomized study, designed to evaluate the influence of somatosensory stimulation on JTHFT performance. Setting: A research laboratory. Participants: Nine patients with chronic stroke (>= 1.5y) who acutely had marked weakness (paralysis of the upper extremity is evaluated as equal or below Medical Research Council [MRC] grade 2) followed by improvement to an MRC grade of 4.24 +/- 0.43 (range, 3.5-4.9) and Fugl-Meyer Assessment (FMA) score of 86.43%+/- 2.02% at the time of testing. Interventions: Two hours of electric somatosensory stimulation was applied to the (1) paretic hand, (2) paretic leg, or (3) no stimulation in different sessions, in a randomized order. Main Outcome Measure: The time required to complete the JTHFT was analyzed by using repeated-measures analysis of variance (ANOVA) with factors time (pre-, postintervention) and intervention (paretic hand, paretic leg, no stimulation) followed by post hoc testing. Results: Significant effects of intervention and intervention by time interaction (P <.01) on JTHFT time was revealed by repeated-measures ANOVA. Post hoc testing documented improvements in JTHFT time with paretic hand stimulation alone (P <.005), an effect that appeared more prominent in subjects with lower FMA scores. Conclusions: Somatosensory stimulation applied to a paretic limb can benefit performance of a functional test in patients with chronic stroke. This result supports the proposal that electric sensory stimulation in combination with training protocols may enhance the benefit of customary neurorehabilitative treatments and possibly motor learning. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20817 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov NR 53 TC 70 Z9 77 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2006 VL 87 IS 3 BP 351 EP 357 DI 10.1016/j.apmr.2005.11.019 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 021XZ UT WOS:000236020500007 PM 16500168 ER PT J AU Chan, P Mahler, J Travlos, G Nyska, A Wenk, M AF Chan, P Mahler, J Travlos, G Nyska, A Wenk, M TI Induction of thyroid lesions in 14-week toxicity studies of 2 and 4-methylimidazole in Fischer 344/N rats and B6C3F1 mice SO ARCHIVES OF TOXICOLOGY LA English DT Article DE 2 and 4-methylimidazole; thyroid lesions; rats; mice ID ZERO-DOSE CONTROL; CARCINOGENESIS; DISPOSITION; INHIBITION; MECHANISMS; NEOPLASIA; CATTLE; DRUGS AB Fifteen-day and 14-week studies of 2-methylimidazole (2MI) and 4-methylimidazole (4MI) were conducted because of widespread human exposure via ingestion of food products containing the compounds and lack of toxicity data. Groups of five male and five female Fischer rats and B6C3F1 mice were administered 2MI by dosed feed at 0, 1,200, 3,300, or 10,000 ppm or 4MI at 0, 300, 800, or 2,500 ppm for 15 days, and groups of 10 male and 10 female Fischer rats and B6C3F1 mice were administered 2MI or 4MI at 0, 625, 1,250, 2,500, 5,000 or 10,000 ppm for 14 weeks. In the 15-day studies, 2MI induced thyroid follicular-cell hyperplasia and pituitary pars-distalis hypertrophy in rats and thyroid follicular-cell hypertrophy and spleen hematopoietic-cell proliferation in mice; 4MI induced no histopathological changes in rats and mice. In the 14-week studies, 2MI increased concentrations of thyroid-stimulating hormone (TSH) and decreased those of thyroxine (T-4) and triiodothyroxine (T-3) in male and female rats according to the dosage. Incidences of diffuse follicular-cell hyperplasia of the thyroid gland increased significantly in male rats exposed to 1,250 ppm or greater and female rats exposed to 2,500 ppm or greater. Thyroid follicular-cell adenoma was diagnosed in two males in the 10,000-ppm group. A dose-related anemia occurred in female rats. In mice, follicular-cell hypertrophy of the thyroid gland, anemia, splenic hematopoietic-cell proliferation, and hemosiderin in kidney tubules appeared. In rats, 4MI induced tremors and ataxia in the high-dose groups. Serum T-3, T-4, and TSH levels were not altered, and no thyroid lesions occurred. Anemia, hepatocytic vacuolation, testicular degeneration, and prostatic atrophy were observed. In mice, anemia, liver cytoplasmic vacuolization, and renal degeneration and dilation occurred. Our studies demonstrated that, in rats and mice, 2MI induces thyroid hyperplasia and hypertrophy, and both 2MI and 4MI induce anemia; 2MI induces thyroid follicular-cell adenoma in male rats. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Microbiol Associates Inc, Bethesda, MD 20850 USA. RP Chan, P (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov NR 36 TC 13 Z9 14 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD MAR PY 2006 VL 80 IS 3 BP 169 EP 180 DI 10.1007/s00204-005-0018-4 PG 12 WC Toxicology SC Toxicology GA 017TH UT WOS:000235715700007 PM 16180012 ER PT J AU Zhang, JF Zhong, W Cui, TX Hu, X Xu, KF Xie, CQ Xue, CY Gibbons, GH Chen, YQE Yang, MZ Li, L Liu, CY AF Zhang, JF Zhong, W Cui, TX Hu, X Xu, KF Xie, CQ Xue, CY Gibbons, GH Chen, YQE Yang, MZ Li, L Liu, CY TI Generation of an adult smooth muscle cell-targeted Cre recombinase mouse model SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Letter ID SOMATIC MUTAGENESIS; TRANSGENIC MICE C1 Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. NHLBI, Transgen Core, NIH, Bethesda, MD 20892 USA. RP Zhang, JF (reprint author), Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA. FU NHLBI NIH HHS [R01 HL114038, R01 HL088391, R01 HL089544, R01 HL105114] NR 6 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2006 VL 26 IS 3 BP E23 EP E24 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 012WW UT WOS:000235372600039 PM 16484601 ER PT J AU Hu, XL Chang, M Saiki, RK Cargill, MA Begovich, AB Ardlie, KG Criswell, LA Seldin, MF Amos, CI Gregersen, PK Kastner, DL Remmers, EF AF Hu, XL Chang, M Saiki, RK Cargill, MA Begovich, AB Ardlie, KG Criswell, LA Seldin, MF Amos, CI Gregersen, PK Kastner, DL Remmers, EF TI The functional-169T -> C single-nucleotide polymorphism in FCRL3 is not associated with rheumatoid arthritis in white North Americans SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID PADI4 GENE; POPULATION; PTPN22 C1 Celera Diagnost, Alameda, CA USA. Sevacare Life Sci, Genom Collaborat Div, Cambridge, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Texas, Houston, TX USA. N Shore LIJ Inst Med Res, Manhasset, NY USA. NIAMS, NIH, Bethesda, MD USA. RP Hu, XL (reprint author), Celera Diagnost, Alameda, CA USA. NR 14 TC 38 Z9 44 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 2006 VL 54 IS 3 BP 1022 EP 1025 DI 10.1002/art.21636 PG 4 WC Rheumatology SC Rheumatology GA 021XR UT WOS:000236019700036 PM 16508985 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG TI Rehabilitation medicine summit: Building research capacity - Executive summary SO ASSISTIVE TECHNOLOGY LA English DT Article DE rehabilitation science; rehabilitation research; research capacity; research infrastructure; metrics; building capacity AB The advancement of medical science depends on the production, availability, and utilization of new information generated by research. A successful research enterprise depends not only on a carefully designed agenda that responds to clinical and societal needs but also on the research capacity necessary to perform the work. Research that is likely to enhance clinical practice presupposes the existence of a critical mass of investigators working as teams in supportive environments. Unfortunately, far too little research capacity of that kind exists in rehabilitation medicine to ensure a robust future for the field. The "Rehabilitation Medicine Summit: Building Research Capacity" was conceptualized as a way of fashioning a long-term plan to foster the required developments. C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. Natl Inst Hlth, Damascus, MD USA. Boston Univ, Sargent Coll Hlth & Rehabil Serv, Boston, MA 02215 USA. Univ Washington, Ctr Med, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA. Univ Florida, Coll Hlth Profess, Gainesville, FL USA. Powers Pyles Sutter & Verville PC, Washington, DC USA. Univ Texas, Med Branch, Div Rehabil Sci, Galveston, TX 77555 USA. Metrohlth Med Ctr, Rammelkamp Ctr Educ & Res, Cleveland, OH 44109 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Michigan, Dept PM&R, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD SPR PY 2006 VL 18 IS 1 BP 2 EP 14 PG 13 WC Rehabilitation SC Rehabilitation GA 046UZ UT WOS:000237837900002 PM 16796237 ER PT J AU Wendland, JR Lesch, KP Newman, TK Timme, A Gachot-Neveu, H Thierry, B Suomi, SJ AF Wendland, JR Lesch, KP Newman, TK Timme, A Gachot-Neveu, H Thierry, B Suomi, SJ TI Differential functional variability of serotonin transporter and monoamine oxidase a genes in macaque species displaying contrasting levels of aggression-related behavior SO BEHAVIOR GENETICS LA English DT Article DE allelic variation; behavioral genetics; evolution; nonhuman primates ID DEFICIT HYPERACTIVITY DISORDER; RECEPTOR VARIANTS; POLYMORPHISM 5-HTTLPR; EARLY EXPERIENCE; NOVELTY SEEKING; MACACA-MULATTA; RHESUS-MONKEYS; GENUS MACACA; LIFE STRESS; ASSOCIATION AB Functional allelic variation in the transcriptional control region of the serotonin transporter and monoamine oxidase A genes has been associated with anxiety- and aggression-related behavior in humans and, more recently, in nonhuman primates. Here, we have genotyped these polymorphic regions in seven species of the genus Macaca. Macaques exhibit exceptional inter-species variation in aggression-related social behavior as illustrated by recent studies showing overlapping patterns of aggression-based social organization grades and macaque phylogeny. We cloned and sequenced two new alleles of the serotonin transporter gene-linked polymorphic region in Barbary and Tibetan macaques. In addition, we observed that species displaying tolerant societies, with relaxed dominance and high levels of conciliatory tendency, were monomorphic for both the serotonin transporter gene and, with the exception of Tonkean macaques, the monoamine oxidase A gene. In contrast, those species known to exhibit intolerant, hierarchical and nepotistic societies were polymorphic at one or more of these loci. Rhesus (M. mulatta), the most intolerant and hierarchical species of macaques, showed the greatest degree of allelic variation in both genes. Additional investigation of a polymorphic repeat in exon III of the dopamine receptor D4 as well as a repeat/single nucleotide polymorphism in the 3' untranslated region of the dopamine transporter which have both been implicated in the modulation of complex behavior failed to reveal a relationship between allelic variability and social organization grade. Taken together, these findings suggest that genetic variation of serotonergic neurotransmission may play an important role in determining inter-species differences in aggression related behavior in macaques. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Primate Unit, Poolesville, MD 20837 USA. Free Univ Berlin, Inst Human Biol & Anthropol, D-14195 Berlin, Germany. CNRS, Ctr Ecol & Physiol Energet, Strasbourg, France. NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, D-97080 Wurzburg, Germany. RP Wendland, JR (reprint author), NIMH, Clin Sci Lab, 10 Ctr Dr,Bldg 10,Rm 3D41, Bethesda, MD 20892 USA. EM wendlandj@mail.nih.gov RI Wendland, Jens/A-1809-2012; Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X FU Intramural NIH HHS NR 51 TC 65 Z9 66 U1 7 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD MAR PY 2006 VL 36 IS 2 BP 163 EP 172 DI 10.1007/s10519-005-9017-8 PG 10 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 038BC UT WOS:000237191600001 PM 16402281 ER PT J AU Bice, PJ Foroud, T Carr, LG Zhang, LL Liu, LX Grahame, NJ Lumeng, L Li, TK Belknap, JK AF Bice, PJ Foroud, T Carr, LG Zhang, LL Liu, LX Grahame, NJ Lumeng, L Li, TK Belknap, JK TI Identification of QTLs influencing alcohol preference in the high alcohol preferring (HAP) and low alcohol preferring (LAP) mouse lines SO BEHAVIOR GENETICS LA English DT Article DE alcohol preference; HAP and LAP mice; QTL; selective breeding ID QUANTITATIVE TRAIT LOCI; 5-HT1B RECEPTOR GENE; RAT LINES; ANTISOCIAL ALCOHOLISM; NUCLEUS-ACCUMBENS; GABA(A) RECEPTORS; R100Q MUTATION; ASSOCIATION; MICE; ETHANOL AB The High- and Low-Alcohol Preferring (HAP1/LAP1 and HAP2/LAP2) mouse lines were developed by selective breeding for differences in alcohol preference. They represent the only extant selectively bred mouse lines developed for this alcohol phenotype. Therefore, they provide a unique resource for QTL detection and mapping. Importantly, neither of the replicate lines is inbred and therefore, novel study designs can be employed to detect loci contributing to alcohol preference. Two independent studies, with very different approaches, were conducted in the HAP and LAP replicate lines. In Study 1, microsatellite markers were genotyped in the replicate HAP1/LAP1 and HAP2/LAP2 mice in QTL regions nominated by other mouse RI and F2 studies in order to detect divergence of allele frequencies in the two oppositely selected lines. Significant differences in allele frequencies were observed in the HAP1/LAP1 mice with markers on chromosome 9 (p < 0.01). In the HAP2/LAP2 mice, significant differences in allele frequencies were identified on chromosomes 2 and 9 (p < 0.01). In Study 2, a genome-wide screen was performed in a sample of 432 HAP1xLAP1 F2 animals and a QTL on chromosome 9 (LOD=5.04) was found which met criteria for genome wide significance (p < 0.001). Gender specific analyses supported a greater effect of the QTL among female mice (LOD=5.19; p < 0.0008) than male mice (LOD=1.19). This study provides additional evidence and confirmation that specific regions on chromosomes 9 and perhaps 2 are important for alcohol preference. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46202 USA. NIAAA, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, VA Med Ctr R&D5, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Bice, PJ (reprint author), Indiana Univ, Sch Med, Dept Med, Room 411,975 W Walnut St, Indianapolis, IN 46202 USA. EM pbice@iupui.edu FU NIAAA NIH HHS [K02 AA00285, KO1 AA000296, P60 AA010760] NR 61 TC 24 Z9 25 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD MAR PY 2006 VL 36 IS 2 BP 248 EP 260 DI 10.1007/s10519-005-9019-6 PG 13 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 038BC UT WOS:000237191600009 PM 16482403 ER PT J AU Le Foll, B Wiggins, M Goldberg, SR AF Le Foll, B Wiggins, M Goldberg, SR TI Nicotine pre-exposure does not potentiate the locomotor or rewarding effects of Delta-9-tetrahydrocannabinol in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cannabinoids; conditioning; locomotion; nicotine; place preference; rat; reward; sensitization; Delta-9-tetrahydrocannabinol ID CONDITIONED PLACE PREFERENCE; SQUIRREL-MONKEYS; DELTA(9)-TETRAHYDROCANNABINOL THC; BEHAVIORAL SENSITIZATION; PSYCHOACTIVE INGREDIENT; DISCRIMINATIVE-STIMULUS; INCENTIVE-SENSITIZATION; TASTE-AVERSIONS; DRUG-USE; MARIJUANA AB This study assessed the effects of nicotine pre-exposure on subsequent locomotor and rewarding effects of repeated Delta-9-tetrahydrocannabinol administration in Sprague-Dawley rats. Repeated administration of the same dose of Delta-9-tetrahydrocannabinol (0.01-2 mg/kg) did not produce significant tolerance or behavioral sensitization to Delta-9-tetrahydrocannabinol's locomotor effects. An unbiased place conditioning paradigm was then used to obtain a measure of the rewarding effects of Delta-9-tetrahydrocannabinol. Rats received an injection of either Delta-9-tetrahydrocannabinol (0.01-2 mg/kg) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials) of a two-compartment apparatus. Control rats received saline injections associated with both compartments. Significant conditioned place preferences developed with 0.1 mg/kg Delta-9-tetrahydrocannabinol in control rats, but not in nicotine pre-exposed rats. Surprisingly, significant place aversions developed at higher 1 and 2 mg/kg doses of Delta-9-tetrahydrocannabinol in nicotine pre-exposed rats. To the extent that behavioral sensitization may reflect reward processes in drug dependence, the lack of behavioral sensitization on repeated Delta-9-tetrahydrocannabinol administration is consistent with the difficulties usually encountered in demonstrating rewarding or reinforcing effects of Delta-9-tetrahydrocannabinol in rats. The present findings suggest, moreover, that nicotine pre-exposure alters the qualitative nature of rewarding effects and accentuates aversive effects of Delta-9-tetrahydrocannabinol. C1 NIDA, Preclin Pharmacol Sect, NIH, Behav Neurosci Res Branch,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Le Foll, B (reprint author), NIDA, Preclin Pharmacol Sect, NIH, Behav Neurosci Res Branch,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM blefoll@intra.nida.nih.gov RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 FU Intramural NIH HHS NR 37 TC 26 Z9 27 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAR PY 2006 VL 17 IS 2 BP 195 EP 199 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 031TV UT WOS:000236727900010 PM 16495727 ER PT J AU Transue, TR Gabel, SA London, RE AF Transue, TR Gabel, SA London, RE TI NMR and crystallographic characterization of adventitious borate binding by trypsin SO BIOCONJUGATE CHEMISTRY LA English DT Article ID BORONIC ACID INHIBITOR; ALPHA-LYTIC PROTEASE; DYNAMIC FREQUENCY-SHIFTS; BORIC-ACID; FLUOROBENZENEBORONIC ACIDS; H-1-NMR SPECTROSCOPY; SUBTILISIN CARLSBERG; STRUCTURAL-ANALYSIS; CRYSTAL-STRUCTURE; CYTOCHROME-C AB Recent B-11 NMR studies of the formation of ternary complexes of trypsin, borate, and SI-binding alcohols revealed evidence for an additional binding interaction external to the enzyme active site. We have explored this binding interaction as a prototypical interaction of borate and boronate ligands with residues on the protein surface. NMR studies of trypsin in which the active site is blocked with leupeptin or with the irreversible inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) indicate the existence of a low-affinity borate binding site with an apparent dissociation constant of 97 nM, measured at pH 8.0. Observation of a field-dependent dynamic frequency shift of the B-11 resonance indicates that it corresponds to a complex for which omega tau >> 1. The 0. 12 ppm shift difference of the borate resonances measured at 11.75 and 7.05 T, corresponds to a quadrupole coupling constant of 260 kHz. A much larger 2.0 ppm shift is observed in the B-11 NMR spectra of trypsin complexed with benzene boronic acid (BBA), leading to a calculated quadrupole coupling constant of 1.1 MHz for this complex. Crystallographic studies identify the second borate binding site as a serine-rich region on the surface of the molecule. Specifically, a complex obtained at pH 10.6 shows a borate ion covalently bonded to the hydroxyl oxygen atoms of Scr164 and Ser167, with additional stabilization coming from two hydrogen-bonding interactions. A similar structure, although with low occupancy (30%), is observed for a trypsin-BBA complex. In this case, the BBA is also observed in the active site, covalently bound in two different conformations to both His57 N epsilon and Ser195 O gamma. An analysis of pairwise hydroxyl oxygen distances was able to predict the secondary borate binding site in porcine trypsin, and this approach is potentially useful for prediction of borate binding sites on the surfaces of other proteins. However, the distances between the Ser164/Ser167 O gamma atoms in all of the reported trypsin crystal structures is significantly greater than the O gamma distances of 2.2 and 1.9 (A) over circle observed in the trypsin complexes with borate and BBA, respectively. Thus, the ability of the hydroxyl oxygens to adopt a sufficiently close orientation to allow bidentate ligation is a critical limit on the borate binding affinity of surface-accessible serine/threonine/tyrosineresidues. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Transue, TR (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS NR 41 TC 13 Z9 13 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 2006 VL 17 IS 2 BP 300 EP 308 DI 10.1021/bc0502210 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 024WD UT WOS:000236226200008 PM 16536459 ER PT J AU Bazinet, RP Rao, JS Chang, L Rapoport, SI Lee, HJ AF Bazinet, RP Rao, JS Chang, L Rapoport, SI Lee, HJ TI Chronic carbamazepine decreases the incorporation rate and turnover of arachidonic acid but not docosahexaenoic acid in brain phospholipids of the unanesthetized rat: Relevance to bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE carbannazepine; arachidonic acid; docosahexaenoic acid; brain; bipolar disorder; kinetics ID PLACEBO-CONTROLLED TRIAL; CENTRAL-NERVOUS-SYSTEM; ALPHA-LINOLENIC ACID; FATTY-ACID; CHRONIC LITHIUM; DOUBLE-BLIND; MOOD STABILIZERS; NUTRITIONAL DEPRIVATION; VALPROIC ACID; CYCLIC-AMP AB The basis for carbamzepine's efficacy in treating bipolar disorder is not agreed on. One hypothesis is that, similar to lithium and valproate (antibipolar drugs), carbamzepine might selectively decrease the kinetics of arachidonic acid (AA) in brain phospholipids. To assess whether it targets brain AA kinetics, we administered carbamzepine (25 mg/kg/day, IP) to rats for 30 days and then determined its effect compared with that of vehicle on incorporation and turnover rates of AA and docosahexaenoic acid (DHA) in brain phospholipids. In unanesthetized rats that had received carbamzepine or vehicle, [1-C-14]AA or [1-C-14]DHA was infused intravenously, and arterial blood plasma was sampled until the animal was killed at 5 min and its brain, after being microwaved, was used for acyl-coenzyme A (acyl-CoA) and phospholipid fatty acid analysis. Chronic carbamzepine, compared with vehicle, decreased the rate of incorporation of AA-CoA (27%-29%) and turnover of AA (25%-27%) but not of DHA-CoA or DHA in brain phospholipids. The results, which are comparable to published findings after chronic administration of lithium and valporic acid to rats, support the hypothesis that drugs effective against mania in bipolar disorder act by selectively downregulating the incorporation of AA-CoA and turnover of AA in brain phospholipids. C1 NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. RP Lee, HJ (reprint author), NIA, NIH, Brain Physiol & Metab Sect, 9000 Rockville Pike,Bldg 9,Room 1S 126, Bethesda, MD 20892 USA. EM hojoolee@mail.nih.gov RI Rao, Jagadeesh/C-1250-2009 FU Intramural NIH HHS NR 63 TC 66 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2006 VL 59 IS 5 BP 401 EP 407 DI 10.1016/j.biopsych.2005.07.024 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 019PY UT WOS:000235850400003 PM 16182257 ER PT J AU Versace, F Cavallero, C Tona, GD Mozzato, M Stegagno, L AF Versace, F Cavallero, C Tona, GD Mozzato, M Stegagno, L TI Effects of sleep reduction on spatial attention SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE sleep reduction; attention; orienting; alertness; vigilance ID SUSTAINED ATTENTION; DEPRIVATION; PERFORMANCE; TASK; RESTRICTION; ALERTNESS; RECOVERY; INERTIA; BRAIN AB To investigate the effects exerted by sleep loss on specific attentive components the performance to a simple reaction time task and to a cued reaction time task were recorded at regular intervals during days following either 8 or 3 It of uninterrupted sleep. Eleven subjects took part in the experiment. The results show that, notwithstanding a general reduction of alertness produced by sleep curtailment (as indicated by the increase of reaction times in the simple reaction time task), in the cued reaction time task only the reaction times to invalidly cued targets significantly increase, while no difference is observed when attention is summoned by a valid cue. This result suggests that the mechanisms underlying orienting of attention are differentially affected by the reduction of alertness level. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Trieste, Dept Psychol, I-34134 Trieste, Italy. Univ Padua, Dept Gen Psychol, I-35100 Padua, Italy. RP Versace, F (reprint author), Univ Florida, NIMH, Ctr Study Emot & Attent, POB 100165, Gainesville, FL 32610 USA. EM fversace@ufl.edu NR 32 TC 25 Z9 27 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAR PY 2006 VL 71 IS 3 BP 248 EP 255 DI 10.1016/j.biopsycho.2005.04.003 PG 8 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 018JO UT WOS:000235760700005 PM 15978717 ER PT J AU Brown, LM Bradley, MM Lang, PJ AF Brown, LM Bradley, MM Lang, PJ TI Affective reactions to pictures of ingroup and outgroup members SO BIOLOGICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 02-06, 2002 CL WASHINGTON, DC SP Soc Psychophysiol Res DE emotion; ethnicity; picture processing; EMG; startle; skin conductance; ratings; viewing time; ingroup; outgroup ID NERVOUS-SYSTEM MEASURES; SKIN COLOR; RACE; SELF; EMPATHY; RESPONSES; EMOTION; STEREOTYPES; PREJUDICE; AMERICAN AB A pervasive form of social categorization among humans is between its and them. In this study, we assessed emotional reactions when people viewed pictures depicting members of the same or different ethnic group. African American and European American participants viewed a series of pleasant and unpleasant pictures portraying either ingroup or outgroup members, while physiological, behavioral, and evaluative judgments were measured. Two hypotheses were assessed. The outgroup antipathy hypothesis predicts that people will respond to outgroup pictures with more negative affect than to ingroup pictures. In contrast, the ingroup empathy hypothesis predicts that people will show exaggerated (pleasant and unpleasant) affective responses to pictures of ingroup members, due to group identification or personal relevance. The data provided no support for the antipathy hypothesis, whereas facial EMG, skin conductance, rating, and viewing time data lent support to the ingroup empathy hypothesis, in which greater pleasure and displeasure were apparent when viewing ingroup pictures. (c) 2005 Elsevier B.V. All rights reserved. C1 Austin Coll, Dept Psychol, Sherman, TX 75090 USA. Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32610 USA. RP Brown, LM (reprint author), Austin Coll, Dept Psychol, 900 N Grand Ave, Sherman, TX 75090 USA. EM lbrown@austincollege.edu NR 51 TC 62 Z9 66 U1 4 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD MAR PY 2006 VL 71 IS 3 BP 303 EP 311 DI 10.1016/j.biopsycho.2005.06.003 PG 9 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 018JO UT WOS:000235760700011 PM 16054283 ER PT J AU Uthus, EO Ross, SA Davis, CD AF Uthus, EO Ross, SA Davis, CD TI Differential effects of dietary selenium (Se) and folate on methyl metabolism in liver and colon of rats SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE selenium; folate; rat; DNA methylation; one-carbon; metabolism ID GLYCINE N-METHYLTRANSFERASE; ONE-CARBON METABOLISM; ABERRANT CRYPT FORMATION; DNA METHYLATION; THIOREDOXIN REDUCTASE; PLASMA GLUTATHIONE; BINDING-PROTEIN; DEFICIENCY; CANCER; METHIONINE AB A previous Study compared the effects of folate on methyl metabolism in colon and liver of rats fed a selenium-deficient diet (< 3 mu g Se/kg) to those of rats fed a diet containing supranutritional Se (2 mg selenite/kg). The purpose of this study was to investigate the effects of folate and adequate Se (0.2 mg/kg) on methyl metabolism in colon and liver. Weanling, Fischer-344 rats (n=8/diet) were fed diets containing 0 or 0.2 mg selenium (as selenite)/kg and 0 or 2 mg folic acid/kg in a 2 x 2 design. After 70 cl, plasma homocysteine was increased (p < 0.0001) by folate deficiency; this increase was markedly attenuated (p < 0.0001) in rats fed the selenium-deficient diet compared to those fed 0.2 mg Se/kg. The activity of hepatic glycine N-methyltransferase (GNMT), an enzyme involved in the regulation of tissue S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), was increased by folate deficiency (p < 0.006) and decreased by selenium deprivation (p < 0.0003). Colon and liver SAH were highest (p < 0.006) in rats fed deficient folate and adequate selenium. Although folate deficiency decreased liver SAM (p < 0.001), it had no effect on colon SAM. Global DNA methylation was decreased (p < 0.04) by selenium deficiency in colon but not liver; folate had no effect. Selenium deficiency did not affect DNA methyltransferase (Dnmt) activity in liver but tended to decrease (p < 0.06) the activity of the enzyme in the colon. Dietary folate did not affect liver or colon Dnmt. These results in rats fed adequate selenium are similar to previous results found in rats fed supranutritional selenium. This suggests that selenium deficiency appears to be a more important modifier of methyl metabolism than either adequate or supplemental selenium. C1 USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. RP Uthus, EO (reprint author), USDA ARS, Grand Forks Human Nutr Res Ctr, POB 9034, Grand Forks, ND 58202 USA. EM euthus@gfhnrc.ars.usda.gov NR 44 TC 28 Z9 29 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD MAR PY 2006 VL 109 IS 3 BP 201 EP 214 DI 10.1385/BTER:109:3:201 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 040ED UT WOS:000237360900001 PM 16632891 ER PT J AU Pavletic, SZ Martin, P Lee, SJ Mitchell, S Jacobsohn, D Cowen, EW Turner, ML Akpek, G Gilman, A McDonald, G Schubert, M Berger, A Bross, P Chien, JW Couriel, D Dunn, JP Fall-Dickson, J Farrell, A Flowers, MED Greinix, H Hirschfeld, S Gerber, L Kim, S Knobler, RT Lachenbruch, PA Miller, FW Mittleman, B Papadopoulos, E Parsons, SK Przepiorka, D Robinson, M Ward, M Reeve, B Rider, LG Shulman, H Schultz, KR Weisdorf, D Vogelsang, GB AF Pavletic, SZ Martin, P Lee, SJ Mitchell, S Jacobsohn, D Cowen, EW Turner, ML Akpek, G Gilman, A McDonald, G Schubert, M Berger, A Bross, P Chien, JW Couriel, D Dunn, JP Fall-Dickson, J Farrell, A Flowers, MED Greinix, H Hirschfeld, S Gerber, L Kim, S Knobler, RT Lachenbruch, PA Miller, FW Mittleman, B Papadopoulos, E Parsons, SK Przepiorka, D Robinson, M Ward, M Reeve, B Rider, LG Shulman, H Schultz, KR Weisdorf, D Vogelsang, GB TI Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. Response Criteria Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogencic cell transplantation; response criteria; consensus ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; SLEEP QUALITY INDEX; CANCER-PATIENTS; PINCH STRENGTH; PSYCHOMETRIC EVALUATION; RHEUMATOID-ARTHRITIS; SYMPTOM-INVENTORY; RANDOMIZED-TRIAL; ACTIVITIES SCALE AB The lack of standardized criteria for quantitative measurement of therapeutic response in clinical trials poses a major obstacle for the development of new agents in chronic g-raft-versus-host disease (GVHD). This consensus document was developed to address several objectives for response criteria to be used in chronic GVHD-related clinical trials. The proposed measures should be practical for use both by transplantation and nontransplantation medical providers, adaptable for use in adults and in children, and focused on the most important chronic GVHD manifestations. The measures should also give preference to quantitative, rather than semiquantitative, measures; capture information regarding signs, symptoms, and function separately from each other; and use validated scales whenever possible to demonstrate improved patient outcomes and meet requirements for regulatory approval of novel agents. Based on these criteria, we propose a set of measures to be considered for use in clinical trials, and forms for data collection are provided (http://www.asbmt.org/ GvHDForms). Measures should be made at 3-month intervals and whenever major changes are made in treatment. Provisional definitions of complete response, partial response, and progression are proposed for each organ and for overall outcomes. The proposed response criteria are based on current expert consensus opinion and are intended to improve consistency in the conduct and reporting of chronic GVHD trials, but their use remains to be demonstrated in practice. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Natl Inst Nursing Res, NIH, Bethesda, MD USA. Med Univ Vienna, Vienna, Austria. NIEHS, NIH, Bethesda, MD USA. NIAMSD, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Tennessee, Memphis, TN USA. NEI, NIH, Bethesda, MD 20892 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Univ Minnesota, Minneapolis, MN USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov RI Hirschfeld, Steven/E-2987-2016; OI Hirschfeld, Steven/0000-0003-0627-7249; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS; NCI NIH HHS [R01 CA118953] NR 66 TC 233 Z9 245 U1 2 U2 5 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2006 VL 12 IS 3 BP 252 EP 266 DI 10.1016/j.bbmt.2006.01.008 PG 15 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 024JF UT WOS:000236190600002 PM 16503494 ER PT J AU Reynolds, MM Hrabie, JA Oh, BK Politis, JK Citro, ML Keefer, LK Meyerhoff, ME AF Reynolds, MM Hrabie, JA Oh, BK Politis, JK Citro, ML Keefer, LK Meyerhoff, ME TI Nitric oxide releasing polyurethanes with covalently linked diazeniumdiolated secondary amines SO BIOMACROMOLECULES LA English DT Article ID IMPROVED BLOOD COMPATIBILITY; SEGMENTED POLYURETHANES; BIOMEDICAL APPLICATION; CHEMICAL SENSORS; POLYMERIC FILMS; THROMBORESISTANT; GRAFTS; DESIGN; PLASMA AB Two novel strategies for synthesizing stable polyurethanes (PUs) capable of generating bioactive nitric oxide (NO) are described. The methods rely on covalently attaching diazeniumdiolate (N2O2-) groups onto secondary amine nitrogens at various positions within the polymer chain such that, when in contact with water or physiological fluids, only the two molecules of NO available from each diazeniumdiolate moiety are released into the surrounding medium, with potential byproducts remaining covalently bound to the matrix. Extensive analysis of the NO, products released from the polymers was employed to develop appropriate strategies to better stabilize the diazeniumdiolate-based polymer structures. In one approach, diazeniumdiolate groups are attached to secondary amino nitrogens of alkane diamines inserted within the diol chain extender of a PU material. Oxidative loss of NO was minimized by blending the polymer with a biocompatible, relatively normucleophilic salt before exposing solutions of the polymer to NO during the diazeniumdiolation step. Fluxes of molecular NO from such materials during immersion in physiological buffer reached levels as high as 19 pmol center dot cm(-2)center dot s(-1) with a total recovery of 21 nmol of NO/mg of PU. A second general synthetic strategy involved omega-haloalkylating the urethane nitrogens and then displacing the halide from the resulting polymer with a nucleophilic polyamine to form a PU with pendent amino groups suitable for diazenitundiolation. Commercially available Pellethane 2363-80AE that was bromobutylated and then reacted with diethylenetriamine and further exposed to gaseous NO proved stable in solid form for several months, but released NO with a total recovery of 17 nmol/mg upon immersion in physiological buffer. This material showed an initial NO flux of 14 pmol center dot cm(-2)center dot s(-1) when immersed in pH 7.4 buffer at 37 degrees C, with gradually decreasing but still observable fluxes for up to 6 days. C1 Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. SAIC Frederick Inc, Basic Res Program, Natl Canc Inst, Frederick, MD 21702 USA. NCI, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Meyerhoff, ME (reprint author), Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. EM mmeyerho@umich.edu RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIBIB NIH HHS [EB-000783] NR 32 TC 53 Z9 54 U1 3 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD MAR PY 2006 VL 7 IS 3 BP 987 EP 994 DI 10.1021/bm060028o PG 8 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 023OP UT WOS:000236136400048 PM 16529441 ER PT J AU Chen, JB Chatterjee, N AF Chen, JB Chatterjee, N TI Haplotype-based association analysis in cohort and nested case-control studies SO BIOMETRICS LA English DT Article DE cohort study; Cox proportional hazards model; nested case-control study; unphased genotype data ID REGRESSION-MODEL; GENOTYPE DATA; UNRELATED INDIVIDUALS; LIKELIHOOD; DISEASE; POLYMORPHISM; PREVENTION; INFERENCE; FUTURE AB Genetic epidemiologic studies often collect genotype data at multiple loci within a genomic region of interest from a sample of unrelated individuals. One popular method for analyzing such data is to assess whether haplotypes, i.e., the arrangements of alleles along individual chromosomes, are associated with the disease phenotype or not. For many study subjects, however, the exact haplotype configuration on the pair of homologous chromosomes cannot be derived with certainty from the available locus-specific genotype data (phase ambiguity). In this article, we consider estimating haplotype-specific association parameters in the Cox proportional hazards model, using genotype, environmental exposure, and the disease endpoint data collected from cohort or nested case-control studies. We study alternative Expectation-Maximization algorithms for estimating haplotype frequencies from cohort and nested case-control studies. Based on a hazard function of the disease derived from the observed genotype data, we then propose a semiparametric method for joint estimation of relative-risk parameters and the cumulative baseline hazard function. The method is greatly simplified under a rare disease assumption, for which an asymptotic variance estimator is also proposed. The performance of the proposed estimators is assessed via simulation studies. An application of the proposed method is presented, using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Chen, JB (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM chenin@mail.nih.gov NR 26 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD MAR PY 2006 VL 62 IS 1 BP 28 EP 35 DI 10.1111/j.1541-0420.2005.00406.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 026CX UT WOS:000236315400005 PM 16542226 ER PT J AU Chatterjee, N Kalaylioglu, Z Shih, JH Gail, MH AF Chatterjee, N Kalaylioglu, Z Shih, JH Gail, MH TI Case-control and case-only designs with genotype and family history data: Estimating relative risk, residual familial aggregation, and cumulative risk SO BIOMETRICS LA English DT Article DE ascertainment correction; Copula model; kin-cohort; multivariate survival; penetrance ID KIN-COHORT DESIGNS; FAILURE TIME DATA; ESTIMATING PENETRANCE; SURVIVAL-DATA; ASSOCIATION; DISEASE; MODELS; DISTRIBUTIONS; MUTATIONS; ASHKENAZI AB In case-control studies of inherited diseases, participating subjects (probands) are often interviewed to collect detailed data about disease history and age-at-onset information in their family members. Genotype data are typically collected from the probands, but not from their relatives. In this article, we introduce an approach that combines case-control analysis of data on the probands with kin-cohort analysis of disease history data on relatives. Assuming a marginally specified multivariate survival model for joint risk of disease among family members, we describe methods for estimating relative risk, cumulative risk, and residual familial aggregation. We also describe a variation of the methodology that can be used for kin-cohort analysis of the family history data from a sample of genotyped cases only. We perform simulation studies to assess performance of the proposed methodologies with correct and misspecified models for familial aggregation. We illustrate the proposed methodologies by estimating the risk of breast cancer from BRCA1/2 mutations using data from the Washington Ashkenazi Study. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Informat Management Serv Inc, Rockville, MD 20852 USA. NCI, Div Canc Treatment & Diagnosis, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6210 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov NR 33 TC 23 Z9 23 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2006 VL 62 IS 1 BP 36 EP 48 DI 10.1111/j.1541-0420.2005.00442.x PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 026CX UT WOS:000236315400006 PM 16542227 ER PT J AU Carroll, RJ Midthune, D Freedman, LS Kipnis, V AF Carroll, RJ Midthune, D Freedman, LS Kipnis, V TI Seemingly unrelated measurement error models, with application to nutritional epidemiology SO BIOMETRICS LA English DT Article DE akaike information criterion; Bayes information criterion; latent variables; measurement error; mixed models; model averaging; model selection; nutritional epidemiology; seemingly unrelated regression ID DIETARY MEASUREMENT ERROR; CANCER; PARAMETERS; SAMPLE; COHORT; RISK; BIAS AB Motivated by an important biomarker study in nutritional epidemiology, we consider the combination of the linear mixed measurement error model and the linear seemingly unrelated regression model, hence Seemingly Unrelated Measurement Error Models. In our context, we have data oil protein intake and energy (caloric) intake from both a food frequency questionnaire (FFQ) and a biomarker, and wish to understand the measurement error properties of the FFQ for each nutrient. Our idea is to develop separate marginal mixed measurement error models for each nutrient, and then combine them into a larger multivariate measurement error model: the two measurement error models are seemingly unrelated because they concern different nutrients, but aspects of each model are highly correlated. As in any seemingly unrelated regression context, the hope is to achieve gains in statistical efficiency compared to fitting each model separately. We show that if we employ a "full" model (fully parameterized), the combination of the two measurement error models leads to no gain over considering each model separately. However, there is also a scientifically motivated "reduced" model that sets certain parameters in the "full" model equal to zero, and for which the combination of the two measurement error models leads to considerable gain over considering each model separately, e.g., 40% decrease in standard errors. We use the Akaike information criterion to distinguish between the two possibilities, and show that the resulting estimates achieve major gains in efficiency. We also describe theoretical and serious practical problems with the Bayes information criterion in this context. C1 Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Bar Ilan Univ, Dept Math Stat & Comp Sci, IL-52900 Ramat Gan, Israel. Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel. RP Carroll, RJ (reprint author), Texas A&M Univ, Dept Stat, TAMU 3143, College Stn, TX 77843 USA. EM carroll@stat.tamu.edu FU NCI NIH HHS [CA-57030]; NIEHS NIH HHS [P30-ES09106] NR 18 TC 19 Z9 20 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2006 VL 62 IS 1 BP 75 EP 84 DI 10.1111/j.1541-0420.2005.00400.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 026CX UT WOS:000236315400011 PM 16542232 ER PT J AU Cosyn, L Gao, ZG Van Rompaey, P Lu, CR Jacobson, KA Van Calenbergh, S AF Cosyn, L Gao, ZG Van Rompaey, P Lu, CR Jacobson, KA Van Calenbergh, S TI Synthesis of hypermodified adenosine derivatives as selective adenosine A(3) receptor ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE adenosine A(3) receptor; selectivity; affinity; ribose and purine modifications ID MAST-CELLS; PART I; ANTAGONISTS; AGONISTS; BINDING; STIMULATION; ACTIVATION; EFFICACY; POTENT AB We investigated the A(3)AR affinity and selectivity of a series of 2-substituted 3'-azido and 3'-amino adenosine derivatives as well as some 5-uronamide derivatives thereof. All compounds showed high A3AR selectivity. While the 3'-azides appeared to be A3AR antagonists with moderate A3AR affinity, their 3'-amino congeners exhibit significantly improved A3AR affinity and behave as partial agonists. For both the 3'-azides and the 3'-amines, the 5'-methylcarbamoyl modification improved the overall affinity. Introduction of a 2-phenylethynyl substituent provided high affinity for the A3AR. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIDDKD, Mol Recognit Sect,LBC, Bioorgan Chem Lab,NIDDK, DHHS,NIH, Bethesda, MD 20892 USA. Univ Ghent, Lab Med Chem FFW, B-9000 Ghent, Belgium. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect,LBC, Bioorgan Chem Lab,NIDDK, DHHS,NIH, Bldg 8A,Rm B1 A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov; serge.vancalenbergh@ugent.be RI Van Calenbergh, Serge/A-3167-2008; Jacobson, Kenneth/A-1530-2009; OI Van Calenbergh, Serge/0000-0002-4201-1264; Jacobson, Kenneth/0000-0001-8104-1493; Lu, Changrui/0000-0002-2171-9888 FU Intramural NIH HHS [Z01 DK031117-20] NR 30 TC 11 Z9 11 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 1 PY 2006 VL 14 IS 5 BP 1403 EP 1412 DI 10.1016/j.bmc.2005.09.062 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 011CE UT WOS:000235244400011 PM 16266807 ER PT J AU Vercouillie, J Mavel, S Galineau, L Ragusa, T Innis, R Kassiou, M Chalon, S Dolle, F Besnard, JC Guilloteau, D Emond, P AF Vercouillie, J Mavel, S Galineau, L Ragusa, T Innis, R Kassiou, M Chalon, S Dolle, F Besnard, JC Guilloteau, D Emond, P TI Synthesis and in vitro evaluation of novel derivatives of diphenylsulfide as serotonin transporter ligands SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE SERT; diphenylsulfide derivatives; MADAM derivatives; monoamine transporters ID POSITRON-EMISSION-TOMOGRAPHY; LIVER-MICROSOMES; IMAGING AGENT; RADIOTRACERS; INVOLVEMENT; DEPRESSION; RECEPTORS; SULFIDES; DISEASE; SYSTEM AB As the serotonin transporter (SERT) is involved in several neurodegenerative and psychiatric disorders, radiopharmaceuticals to image the SERT by PET or SPECT would be very valuable in studying these diseases. For the development of imaging agents, we have synthesized novel derivatives of recently reported diphenylsulfide SERT ligands, in which the sulfur atom linking the two phenyl rings was replaced by an oxygen, sulfinyl, sulfonyl, amino or carbon group. Three of these exhibited good to high in vitro affinity (0.5 nM < K-i < 11 nM) and selectivity for the SERT over the other monoamine transporters. (C) 2005 Elsevier Ltd. All rights reserved. C1 Univ Tours, INSERM, U619, Lab Biophys Med & Pharmaceut, F-37200 Tours, France. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Royal Prince Alfred Hosp, Dept PET & Nucl Med, Sydney, NSW 2050, Australia. Univ Sydney, Dept Pharmacol, Sydney, NSW 2006, Australia. CEA, SHFJ, F-91401 Orsay, France. RP Emond, P (reprint author), Univ Tours, INSERM, U619, Lab Biophys Med & Pharmaceut, 31 Ave Monge, F-37200 Tours, France. EM emond@univ-tours.fr RI Emond, Patrick/P-6994-2016; Galineau, Laurent/P-8140-2016; MAVEL, Sylvie/P-9001-2016; Chalon, Sylvie/G-2734-2013 OI Emond, Patrick/0000-0002-5324-2164; Galineau, Laurent/0000-0003-4960-1643; MAVEL, Sylvie/0000-0002-1424-2698; Chalon, Sylvie/0000-0003-1865-8380 FU NIMH NIH HHS [K02MH01366, N01MH80005] NR 28 TC 12 Z9 12 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAR 1 PY 2006 VL 16 IS 5 BP 1297 EP 1300 DI 10.1016/j.bmcl.2005.11.066 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 011RB UT WOS:000235284700040 PM 16337793 ER PT J AU Holmgren, M Rakowski, RF AF Holmgren, M Rakowski, RF TI Charge translocation by the Na+/K+ pump under Na+/Na+ exchange conditions: Intracellular Na+ dependence SO BIOPHYSICAL JOURNAL LA English DT Article ID XENOPUS-OOCYTES; VOLTAGE-DEPENDENCE; SODIUM-PUMP; NA/K PUMP; ION CHANNELS; NA,K PUMP; NA,K-ATPASE; BINDING; ADP; K+ AB The effect of intracellular (i) and extracellular (o) Na+ on pre-steady-state transient current associated with Na+/Na+ exchange by the Na+/K+ pump was investigated in the vegetal pole of Xenopus oocytes. Current records in response to 40-ms voltage pulses from -180 to +100 mV in the absence of external Na+ were subtracted from current records obtained under Na+/Na+ exchange conditions. Na+-sensitive transient current and dihydroouabain-sensitive current were equivalent. The quantity of charge moved ( Q) and the relaxation rate coefficient (k(tot)) of the slow component of the Na-o(+)-sensitive transient current were measured for steps to various voltages (V). The data were analyzed using a four- state kinetic model describing the Na+ binding, occlusion, conformational change, and release steps of the transport cycle. The apparent valence of the Q vs. V relationship was near 1.0 for all experimental conditions. When extracellular Na+ was halved, the midpoint voltage of the charge distribution (V-q) shifted -025.3 +/- 0.4 mV, which can be accounted for by the presence of an extracellular ion-well having a dielectric distance delta = 0.69 +/- 0.01. The effect of changes of Na+ ion Na-o(+)-sensitive transient current was investigated. The midpoint voltage (V-q) of the charge distribution curve was not affected over the Na-o(+) concentration range 3.13 - 50 mM. As Na-i(+) was decreased, the amount of charge measured and its relaxation rate coefficient decreased with an apparent K-m of 3.2 +/- 0.2 mM. The effects of lowering Na-i(+) on pre-steady-state transient current can be accounted for by decreasing the charge available to participate in the fast extracellular Na+ release steps, by a slowly equilibrating (phosphorylation/occlusion) step intervening between intracellular Na+ binding and extracellular Na+ release. C1 NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA. Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA. RP Rakowski, RF (reprint author), NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA. EM rakowski@ohio.edu FU NINDS NIH HHS [R01 NS022979-20, NS-22979, R01 NS022979, R01 NS022979-19A2] NR 32 TC 15 Z9 15 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2006 VL 90 IS 5 BP 1607 EP 1616 DI 10.1529/biophysj.105.072942 PG 10 WC Biophysics SC Biophysics GA 010ZA UT WOS:000235235600015 PM 16326910 ER PT J AU Danelon, C Nestorovich, EM Winterhalter, M Ceccarelli, M Bezrukov, SM AF Danelon, C Nestorovich, EM Winterhalter, M Ceccarelli, M Bezrukov, SM TI Interaction of zwitterionic penicillins with the OmpF channel facilitates their translocation SO BIOPHYSICAL JOURNAL LA English DT Article ID OUTER-MEMBRANE PERMEABILITY; BETA-LACTAM ANTIBIOTICS; ESCHERICHIA-COLI; MOLECULAR-DYNAMICS; PORIN CHANNELS; SINGLE-CHANNEL; ION PERMEATION; RESISTANCE; TRANSPORT; SIMULATION AB To study translocation of beta-lactam antibiotics of different size and charge across the outer bacterial membrane, we combine an analysis of ion currents through single trimeric outer membrane protein F ( OmpF) porins in planar lipid bilayers with molecular dynamics simulations. Because the size of penicillin molecules is close to the size of the narrowest part of the OmpF pore, penicillins occlude the pore during their translocation. Favorably interacting penicillins cause time-resolvable transient blockages of the small-ion current through the channel and thereby provide information about their dynamics within the pore. Analyzing these random fluctuations, we find that ampicillin and amoxicillin have a relatively high affinity for OmpF. In contrast, no or only a weak interaction is detected for carbenicillin, azlocillin, and piperacillin. Molecular dynamics simulations suggest a possible pathway of these drugs through the OmpF channel and rationalize our experimental findings. For zwitterionic ampicillin and amoxicillin, we identify a region of binding sites near the narrowest part of the channel pore. Interactions with these sites partially compensate for the entropic cost of drug confinement by the channel. Whereas azlocillin and piperacillin are clearly too big to pass through the channel constriction, dianionic carbenicillin does not find an efficient binding region in the constriction zone. Carbenicillin's favorable interactions are limited to the extracellular vestibule. These observations confirm our earlier suggestion that a set of high-affinity sites at the narrowest part of the OmpF channel improves a drug's ability to cross the membrane via the pore. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Inst Pharmacol & Biol Struct, Toulouse, France. Int Univ Bremen, Bremen, Germany. Univ Cagliari, Dept Phys, I-09042 Monserrato, Italy. Univ Cagliari, Sardinian Lab Computat Mat Sci, I-09042 Monserrato, Italy. RP Danelon, C (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1N-124B, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU Intramural NIH HHS NR 61 TC 86 Z9 87 U1 1 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2006 VL 90 IS 5 BP 1617 EP 1627 DI 10.1529/biophysj.105.075192 PG 11 WC Biophysics SC Biophysics GA 010ZA UT WOS:000235235600016 PM 16339889 ER PT J AU Polozov, IV Gawrisch, K AF Polozov, IV Gawrisch, K TI Characterization of the liquid-ordered state by proton MAS NMR SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; HIGH-RESOLUTION PROTON; LATERAL DIFFUSION; MODEL MEMBRANES; LIPID BILAYERS; FLUORESCENCE MICROSCOPY; PHOSPHOLIPID BILAYER; PHYSICAL-PROPERTIES; MOLECULAR-DYNAMICS; NEUTRON-SCATTERING AB We investigated if magic angle spinning (MAS) H-1 NMR can be used as a tool for detection of liquid-ordered domains ( rafts) in membranes. In experiments with the lipids SOPC, DOPC, DPPC, and cholesterol we demonstrated that H-1 MAS NMR spectra of liquid-ordered domains (l(o)) are distinctly different from liquid-disordered (l(d)) and solid-ordered (s(o)) membrane regions. At a MAS frequency of 10 kHz the methylene proton resonance of hydrocarbon chains in the l(d) phase has a linewidth of similar to 50 Hz. The corresponding linewidth is similar to 1 kHz for the l(o) phase and several kHz for the s(o) phase. According to results of H-1 NMR dipolar echo spectroscopy, the broadening of MAS resonances in the lo phase results from an increase in effective strength of intramolecular proton dipolar interactions between adjacent methylene groups, most likely because of a lower probability of gauche/trans isomerization in lo. In spectra recorded as a function of temperature, the onset of lo domain ( raft) formation is seen as a sudden onset of line broadening. Formation of small domains yielded homogenously broadened resonance lines, whereas large lo domains (diameter > 0.3 mu m) in an l(d) environment resulted in superposition of the narrow resonances of the l(d) phase and the much broader resonances of lo. 1 H MAS NMR may be applied to detection of rafts in cell membranes. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Ln,Rm 3N-07, Bethesda, MD 20892 USA. EM gawrisch@helix.nih.gov NR 64 TC 41 Z9 43 U1 3 U2 30 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2006 VL 90 IS 6 BP 2051 EP 2061 DI 10.1529/biophysj.105.070441 PG 11 WC Biophysics SC Biophysics GA 017RA UT WOS:000235709500018 PM 16387785 ER PT J AU Chen, XC Arac, D Wang, TM Gilpin, CJ Zimmerberg, J Rizo, J AF Chen, XC Arac, D Wang, TM Gilpin, CJ Zimmerberg, J Rizo, J TI SNARE-mediated lipid mixing depends on the physical state of the vesicles SO BIOPHYSICAL JOURNAL LA English DT Article ID INTRACELLULAR MEMBRANE-FUSION; HEMIFUSION INTERMEDIATE; SYNAPTIC EXOCYTOSIS; CRYSTAL-STRUCTURE; T-SNARES; COMPLEX; PROTEINS; SYNTAXIN; CALCIUM; YEAST AB Reconstitution experiments have suggested that N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins constitute a minimal membrane fusion machinery but have yielded contradictory results, and it is unclear whether the mechanism of membrane merger is related to the stalk mechanism that underlies physiological membrane fusion. Here we show that reconstitution of solubilized neuronal SNAREs into preformed 100 nm liposomes (direct method) yields proteoliposomes with more homogeneous sizes and protein densities than the standard reconstitution method involving detergent cosolubilization of proteins and lipids. Standard reconstitutions yield slow but efficient lipid mixing at high protein densities and variable amounts of lipid mixing at moderate protein densities. However, the larger, more homogenous proteoliposomes prepared by the direct method yield almost no lipid mixing at moderate protein densities. These results suggest that the lipid mixing observed for standard reconstitutions is dominated by the physical state of the membrane, perhaps due to populations of small vesicles (or micelles) with high protein densities and curvature stress created upon reconstitution. Accordingly, changing membrane spontaneous curvature by adding lysophospholipids inhibits the lipid mixing observed for standard reconstitutions. Our data indicate that the lipid mixing caused by high SNARE densities and/or curvature stress occurs by a stalk mechanism resembling the mechanism of fusion between biological membranes, but the neuronal SNAREs are largely unable to induce lipid mixing at physiological protein densities and limited curvature stress. C1 Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Rizo, J (reprint author), Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. EM jose@arnie.swmed.edu RI Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011 FU NINDS NIH HHS [R01 NS037200, NS37200] NR 59 TC 88 Z9 89 U1 1 U2 16 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2006 VL 90 IS 6 BP 2062 EP 2074 DI 10.1529/biophysj.105.071415 PG 13 WC Biophysics SC Biophysics GA 017RA UT WOS:000235709500019 PM 16361343 ER PT J AU Kameyama, K Minton, AP AF Kameyama, K Minton, AP TI Rapid quantitative characterization of protein interactions by composition gradient static light scattering SO BIOPHYSICAL JOURNAL LA English DT Article ID ALPHA-CHYMOTRYPSIN; SELF-ASSOCIATION; DIMERIZATION; DEPENDENCE; FTSZ AB Two new applications of the recently developed technique of composition gradient static light scattering ( CGSLS) are presented. 1), The method is demonstrated to be capable of detecting and quantitatively characterizing reversible association of chymotrypsin and bovine pancreatic trypsin inhibitor in a solution mixture and simultaneously occurring reversible self-association of chymotrypsin at low pH in the same mixture. The values of equilibrium constants for both self- and heteroassociation may be determined with reasonable precision from the analysis of data obtained from a single experiment requiring < 15 min and < 1 mg of each protein. 2), Analysis of the results of a single CG-SLS experiment carried out on Ftsz, a protein that self-associates to form linear oligomers of indefinite size in the presence of guanosine diphosphate, yields the dependence of the equilibrium constant for monomer addition upon oligomer size. C1 NIDDKD, Lab Biochem & Genet, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Minton, AP (reprint author), NIDDKD, Lab Biochem & Genet, US Dept Hlth & Human Serv, NIH, Bldg 8,Rm 226, Bethesda, MD 20892 USA. EM minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247 FU Intramural NIH HHS NR 14 TC 25 Z9 27 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2006 VL 90 IS 6 BP 2164 EP 2169 DI 10.1529/biophysj.105.074310 PG 6 WC Biophysics SC Biophysics GA 017RA UT WOS:000235709500029 PM 16387762 ER PT J AU Tomanee, P Hsu, JT AF Tomanee, P Hsu, JT TI Preparative fractionation of protein, RNA, and plasmid DNA using centrifugal precipitation chromatography with tubular dialysis membrane inside a convoluted tubing as separation channel SO BIOTECHNOLOGY PROGRESS LA English DT Article ID TANGENTIAL FLOW FILTRATION; GENE-THERAPY; PURIFICATION; CTAB AB Fractionation of clarified E. coli lysate components in bench-scale and preparative-scale centrifugal precipitation chromatography (CPC), using a solution of cationic surfactant cetyltrimethylammonium bromide (CTAB) containing 0.5 M NaCl as precipitant, are compared here. Step gradient of CTAB from 0.50% to 0.16% (w/v) gave a successful fractionation in bench-scale CPC however, a linear gradient of lower CTAB concentration, 0.20-0% (w/v), was used in the preparative scale and resulted in similar fractionation. The preparative-scale CPC has a superior sample loading capacity by the use Of tubular dialysis membrane inside convoluted tubing, as the separation channel. In this study, the quantity of the sample loaded into the preparative CPC was about 15 times more than that in the bench scale, and in a single run the preparative CPC could prepare approximately 3 mg of plastmid DNA with about 96% of RNA removed. The higher Surface area per length of the separation channel in the preparative CPC was believed to benefit mass transfer of CTAB across the membrane, leading, to less CTAB being required in the process. C1 Lehigh Univ, Dept Chem Engn, Biopharmaceut Technol Inst, Bethlehem, PA 18015 USA. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Hsu, JT (reprint author), Lehigh Univ, Dept Chem Engn, Biopharmaceut Technol Inst, Bethlehem, PA 18015 USA. EM jth0@lehigh.edu NR 21 TC 4 Z9 4 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAR-APR PY 2006 VL 22 IS 2 BP 532 EP 537 DI 10.1021/bp058002g PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 032OG UT WOS:000236783400029 PM 16599573 ER PT J AU Vahratian, A Hoffman, MK Troendle, JF Zhang, J AF Vahratian, A Hoffman, MK Troendle, JF Zhang, J TI The impact of parity on course of labor in a contemporary population SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article; Proceedings Paper CT 52nd Annual Clinical Meeting of the American-College-of-Obstetricians-and-Gynecologists CY MAY 01-05, 2004 CL Philadelphia, PA SP Amer Coll Obstetricians & Gynecologists ID WEIGHT-GAIN; GRAPHICOSTATISTICAL ANALYSIS; GRAND MULTIPARA; OBESITY; PREGNANCY; CURVE; CHILDBEARING; PROGRESSION; OVERWEIGHT; DURATION AB Background: Few studies have examined in depth the labor progression of multiparas to determine if there is any additional impact of being parous beyond the first birth. The objective of this study was to determine the effect of parity on labor progression in contemporary obstetric practice. Methods: Our sample consisted of all low-risk women who delivered a term, live-born infant from January 2002 to March 2004 at a single institution in Delaware, United States (n = 5,589). The median duration of labor by each centimeter of cervical dilation was computed for parity = 0 (n = 2,645); parity = 1 (n = 1,839); parity = 2 (n = 750); and parity = 3 + (n = 355). Results: Multiparas had a significantly faster labor progression from 4 to 10 cm (293, 300, and 313 min, respectively, for parity = 1, parity = 2, and parity = 3 +), compared with nulliparas (383 min for parity = 0), as well as a shorter second stage of labor. However, no significant differences were found in duration of the active phase or the second stage of labor among multiparas. Conclusions: Additional childbearing appears to have no effect of on the progression of labor among multiparous subgroups. The difference in duration of the active phase between nulliparas and multiparas is substantially smaller in a contemporary population. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA. RP Vahratian, A (reprint author), Univ Michigan, Dept Obstet & Gynecol, Womens Hosp L4000, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Vahratian, Anjel/A-1182-2011 NR 26 TC 20 Z9 21 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD MAR PY 2006 VL 33 IS 1 BP 12 EP 17 PG 6 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 034MO UT WOS:000236933300003 PM 16499527 ER PT J AU Mackall, CL AF Mackall, CL TI A fine romance: IL-7 and HGF beta SO BLOOD LA English DT Editorial Material ID HEPATOCYTE GROWTH-FACTOR; STIMULATING FACTOR PPBSF; MARROW STROMAL CELLS; IDENTIFICATION C1 NCI, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 1739 EP 1740 DI 10.1182/blood-2005-12-4901 PG 2 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700001 ER PT J AU Derse, D AF Derse, D TI HTLV tax tails SO BLOOD LA English DT Editorial Material ID CELL-GROWTH CONTROL; PDZ DOMAIN; ONCOPROTEIN C1 NCI, Bethesda, MD 20892 USA. RP Derse, D (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 1740 EP 1741 DI 10.1182/blood-2005-12-4960 PG 2 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700002 ER PT J AU Battiwalla, M Hahn, T Radovic, M Roy, H Wahab, A Duman, E Bajwa, R Padmanabhan, S Becker, J Barrett, AJ McCarthy, PL AF Battiwalla, M Hahn, T Radovic, M Roy, H Wahab, A Duman, E Bajwa, R Padmanabhan, S Becker, J Barrett, AJ McCarthy, PL TI Human leukocyte antigen (HLA) DR15 is associated with reduced incidence of acute GVHD in HLA-matched allogeneic transplantation but does not impact chronic GVHD incidence SO BLOOD LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ACQUIRED APLASTIC-ANEMIA; VERSUS-HOST-DISEASE; MYELODYSPLASTIC SYNDROME; MULTIPLE-SCLEROSIS; JAPANESE PATIENTS; HLA-DR15; SUSCEPTIBILITY; PREDICTS; CD4 AB The DR15 allele at the HLA DRB1 locus is a marker for immune-mediated bone marrow failure syndromes. We hypothesized that HLA DR15 plays a role in T-cell interactions with hematopoiesis and investigated the role of HLA DR15 on graft-versus-host disease (GVHD) and graft-versus-leukemia effects in HLA-matched allogeneic blood or marrow transplantation (BMT) performed for myeloid malignancies. We performed a retrospective analysis of 119 consecutive related and 48 consecutive unrelated allogeneic BMT for myeloid malignancies treated between 1991 and 2005 to investigate the influence of HLA DR15 on overall survival (OS), progression-free survival (PFS), and incidence of grades 11 to IV acute GVHD. HLA DR15 was determined by either molecular (n = 108) or serologic (n = 59) methods. The incidence of HLA DR15 was similar to the general white population (35/167 = 21 %).There were no significant differences in transplantation characteristics between the HILA DR15-positive and-negative groups. There was no significant difference in chronic GVHD, OS, or PFS between the H LA DR15-positive versus-negative groups in any disease or donor relation subgroups. The HLA DR15-positive group experienced a significantly lower incidence of acute GVHD grades 11 to IV: 23% versus 42% (P =.041). These results suggest that HLA DR15 reduces the risk of acute GVHD. C1 Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14202 USA. Roswell Pk Canc Inst, Dept Lab Med, Buffalo, NY 14202 USA. Natl Heart Lung & Blood Inst, Hematol Branch, NIH, Bethesda, MD USA. RP Battiwalla, M (reprint author), Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14202 USA. EM minoo.battiwalla@roswellpark.org RI Bajwa, Rajinder/E-2685-2011 NR 32 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 1970 EP 1973 DI 10.1182/blood-2005-05-1958 PG 4 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700040 PM 16282347 ER PT J AU Zhang, R Lifson, JD Chougnet, C AF Zhang, R Lifson, JD Chougnet, C TI Failure of HIV-exposed CD4(+) T cells to activate dendritic cells is reversed by restoration of CD40/CD154 interactions SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD40 LIGAND DYSREGULATION; COSTIMULATORY MOLECULES; ANTIRETROVIRAL THERAPY; ENVELOPE GLYCOPROTEIN; ANTIGEN PRESENTATION; CYTOKINE RESPONSE; INFECTED PATIENTS; IL-12 PRODUCTION; LYMPHOID-TISSUE AB Because interactions between activated CD4(+) T cells and antigen-presenting cells (APCs) are crucial for optimal APC function, defective CD4+ T-cell activation may contribute to APC dysregulation in HIV infection. Here, we show that CD4+ T cells exposed during stimulation to noninfectious HIV having functional envelope glycoproteins failed to provide activation signals to autologous dendritic cells (DCs). Consequently, important DC functions, including production of immunoregulatory cytokines (interleukin-12 p40 and interleukin-10) and up-regulation of costimulatory molecules (CD86, CD40, CD83), as well as the capacity to stimulate naive allogeneic T cells, were all adversely affected. The blunted upregulation of CD154 in CD4(+) T cells that were activated in the presence of noninfectious viruses is likely to be the major underlying mechanism for these defects. Addition of recombinant trimeric CD154 could restore production of cytokines by DCs cocultured with HIV-exposed T cells. Moreover, the functional defects mediated by coculture with HIV-exposed T cells were similar to those following antibody blockade of CD40-CD154 interactions. HIV-mediated blunted CD154 expression may thus play an important role in the suppression of cell-mediated immunity seen in HIV infection. C1 Cincinnati Childrens Hosp, Ctr Med, Div Mol Immunol MLC 7021, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. SAIC Frederick, AIDS Vaccine Program, NCI, Frederick, MD USA. RP Chougnet, C (reprint author), Cincinnati Childrens Hosp, Ctr Med, Div Mol Immunol MLC 7021, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM claire.chougnet@cchmc.org FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [AI 056927, R01 AI056927] NR 51 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 1989 EP 1995 DI 10.1182/blood-2005-07-2731 PG 7 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700043 PM 16269614 ER PT J AU Biswas, SK Gangi, L Paul, S Schioppa, T Saccani, A Sironi, M Bottazzi, B Doni, A Vincenzo, B Pasqualini, F Vago, L Nebuloni, M Mantovani, A Sica, A AF Biswas, SK Gangi, L Paul, S Schioppa, T Saccani, A Sironi, M Bottazzi, B Doni, A Vincenzo, B Pasqualini, F Vago, L Nebuloni, M Mantovani, A Sica, A TI A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappa B and enhanced IRF-3/STAT1 activation) SO BLOOD LA English DT Article ID TOLL-LIKE RECEPTORS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN-MALIGNANT MELANOMA; ALTERNATIVE ACTIVATION; IMMUNE-RESPONSES; NECROSIS-FACTOR; BREAST-CANCER; INFLAMMATION; ANGIOGENESIS; PROGRESSION AB To identify the molecular basis underlying the functions of tumor-associated macrophages (TAMs), we characterized the gene expression profile of TAMs isolated from a murine fibrosarcoma in comparison with peritoneal macrophages (PECs) and myeloid suppressor cells (MSCs), using a cDNA microarray technology. Among the differentially expressed genes, 15 genes relevant to inflammation and immunity were validated by real-time polymerase chain reaction (PCR) and protein production. Resting TAMs showed a characteristic gene expression pattern with higher expression of genes coding for the immunosuppressive cytokine IL-10, phagocytosis-related receptors/molecules (Msr2 and C1q), and inflammatory chemokines (CCL2 and CCL5) as expected, as well as, unexpectedly, IFN-inducible chemokines (CXCL9, CXCL10, CXCL16). Immunohistology confirmed and extended the in vitro analysis by showing that TAMs express M2-associated molecules (eg, IL-10 and MGL1), as well as CCL2, CCL5, CXCL9, CXCL10, and CXCL16, but no appreciable NOS2. Lipopolysaccharide (LPS)-mediated activation of TAMs resulted in defective expression of several proinflammatory cytokines (eg, IL-10, IL-6, TNF-alpha) and chemolkines (eg, CCL3), as opposed to a strong up-regulation of immunosuppressive cytokines (IL-10, TGF beta) and IFN-inducible chemokines (CCL5, CXCL9, CXCL10, CXCL16). Thus, profiling of TAMs from a murine sarcoma revealed unexpected expression of IFN-inducible chemokines, associated with an M2 phenotype (IL-10(high), IL-12(low)), and divergent regulation of the NF-kappa B versus the IRF-3/STAT1 pathway. C1 Ist Clin Humanitas, I-20089 Milan, Italy. NCI, Microarray Res Grp, Lab Mol Technol, SAIC, Frederick, MD USA. Ist Ric Farmacol Mario Negri, Milan, Italy. State Univ Milan, Inst Pathol, Ctr Eccellenza Innovaz Diagnost & Terapeut, Milan, Italy. Univ Padua, Oncol Sect, Dept Oncol & Surg Sci, Padua, Italy. Univ Milan, Dept Clin Sci L Sacco, Inst Pathol, Milan, Italy. RP Mantovani, A (reprint author), Ist Clin Humanitas, Via Manzoni 56, I-20089 Milan, Italy. EM alberto.mantovani@humanitas.it RI Peng, Chunwei/F-6788-2010; OI Bottazzi, Barbara/0000-0002-1930-9257; Mantovani, Alberto/0000-0001-5578-236X; Schioppa, Tiziana/0000-0002-6303-6065 NR 53 TC 340 Z9 364 U1 5 U2 42 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2006 VL 107 IS 5 BP 2112 EP 2122 DI 10.1182/blood-2005-01-0428 PG 11 WC Hematology SC Hematology GA 016PQ UT WOS:000235632700059 PM 16269622 ER PT J AU Smith, SR Ghosh, MC Ollivierre-Wilson, H Tong, WH Rouault, TA AF Smith, SR Ghosh, MC Ollivierre-Wilson, H Tong, WH Rouault, TA TI Complete loss of iron regulatory proteins 1 and 2 prevents viability of murine zygotes beyond the blastocyst stage of embryonic development SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE 5 total-embryogenesis; ferritin; iron metabolism; IRP1; IRP2 ID TRANSFERRIN-RECEPTOR; TARGETED DELETION; IN-VIVO; METABOLISM; MICE; LACTOFERRIN; EXPRESSION; MOUSE; IRP2; NEURODEGENERATION AB Iron regulatory proteins 1 and 2 (IRPs) are homologous mammalian cytosolic proteins that sense intracellular iron levels and post-transcriptionally regulate expression of ferritin, transferrin receptor. and other iron metabolism proteins. Adult mice with homozygous targeted deletion of IRP2 develop microcytic anemia, elevated red cell protoporphyrin IX levels, high serum ferritin, and adult-onset neurodegeneration. Mice with homozygous deletion of IRP1 develop no overt abnormalities, but mice that lack both copies of IRP2 and one copy of IRP1 develop a more severe anemia and neurodegeneration than mice with deletion of IRP2 alone. Here, we have demonstrated that IRP1-/- IRP2-/- embryos do not survive gestation, and that although IRP1-/- IRP2-/blastocysts call be genotyped and harvested, implanted embryos with the IRP1-/- IRP2-/genotype are undetectable at embryonic day 6.5 and beyond. Blastocysts derived from a cross in which 25% of the fertilized embryos were expected to have the IRP1-/- IRP2-/genotype often showed brown discoloration and abnormal morphology. These abnormal blastocysts likely have the IRP1-/- IRP2-/- genotype, and the brown discoloration may be attributable to ferritin overexpression and sequestration of ferric iron ill ferritin, whereas abnormal morphology may be due to concomitant functional iron deficiency. These results demonstrate that IRPs are indispensable for regulation of mammalian iron homeostasis at the post-implantation stage of murine embryonic development. Published by Elsevier Inc. C1 NICHHD, Cell Biol & Metab Branch, Sect Human Iron Metab, Bethesda, MD 20892 USA. RP Smith, SR (reprint author), Childrens Natl Med Ctr, Dept Pediat Crit Care Med, Washington, DC 20010 USA. EM srsmith@cnmc.org; ghoshm@mail.nih.gov; wilsonh@ors.d.nih.gov; tongw@mail.nih.gov; trou@helix.nih.gov NR 24 TC 63 Z9 65 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 1079-9796 EI 1096-0961 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2006 VL 36 IS 2 BP 283 EP 287 DI 10.1016/j.bcmd.2005.12.006 PG 5 WC Hematology SC Hematology GA 030UX UT WOS:000236661600035 PM 16480904 ER PT J AU Gu, YC Bauer, TR Sokolic, RA Hai, M Tuschong, LM Burkholder, T Bacher, J Starost, MF Hickstein, DD AF Gu, YC Bauer, TR Sokolic, RA Hai, M Tuschong, LM Burkholder, T Bacher, J Starost, MF Hickstein, DD TI Conversion of the severe to the moderate disease phenotype with donor leukocyte microchimerism in canine leukocyte adhesion deficiency SO BONE MARROW TRANSPLANTATION LA English DT Article DE leukocyte adhesion deficiency; dog; CD18; integrin; transplant ID BONE-MARROW-TRANSPLANTATION; MIXED HEMATOPOIETIC CHIMERISM; TOTAL-BODY IRRADIATION; T-CELL RESPONSES; PHARMACOLOGICAL IMMUNOSUPPRESSION; GRANULOCYTOPATHY SYNDROME; P150,95 GLYCOPROTEINS; PARTICLE PHAGOCYTOSIS; RECURRENT INFECTIONS; DEFECTIVE ADHERENCE AB Leukocyte adhesion deficiency-1 (LAD-1), a genetic immunodeficiency disease characterized by life-threatening bacterial infections, results from the defective adherence and migration of leukocytes due to mutations in the leukocyte integrin CD18 molecule. Canine LAD (CLAD) represents the canine homologue of the severe phenotype of LAD-1 in children. In previous studies we demonstrated that non-myeloablative stem cell transplantation from matched littermates resulted in mixed donor-host chimerism and reversal of the disease phenotype in CLAD. In this study, we describe two CLAD dogs with less than 2% donor leukocyte chimerism following non-myeloablative transplant. Both dogs are alive more than 24 months after transplant with an attenuated CLAD phenotype resembling the moderate deficiency phenotype of LAD. The improvement in the CLAD phenotype with very low levels of donor CD18(+) leukocytes correlated with the preferential egress of the CD18(+) neutrophils into extravascular sites. The clinical response with very low levels of donor CD18(+) leukocytes in CLAD supports using this model for testing gene therapy strategies since the low levels of gene-corrected hematopoietic cells expected with hematopoietic gene therapy would likely have a therapeutic effect in CLAD. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Gu, YC (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bldg 10 CRC,Room 3-3264,MSC 1203,10 Ctr Dr, Bethesda, MD 20892 USA. EM guyu@mail.nih.gov RI Sokolic, Robert/I-6072-2012 FU Intramural NIH HHS NR 32 TC 9 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2006 VL 37 IS 6 BP 607 EP 614 DI 10.1038/sj.bmt.1705291 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 019LC UT WOS:000235836200011 PM 16444276 ER PT J AU Maertens, J Cornely, OA Winston, DJ Perfect, J Helfgott, D Ullmann, AJ Holowiecki, J Stockelberg, D Goh, YT Petrini, M Walsh, T Boparai, N Hardalo, C Angulo-Gonzalez, D AF Maertens, J Cornely, OA Winston, DJ Perfect, J Helfgott, D Ullmann, AJ Holowiecki, J Stockelberg, D Goh, YT Petrini, M Walsh, T Boparai, N Hardalo, C Angulo-Gonzalez, D TI Prophylaxis of invasive fungal infection with posaconazole or standard azoles (fluconazole/itraconazole) in patients with acute myelogenous leukaemia or myelodysplastic syndrome and chemotherapy-induced neutropenia: results of a randomised multicentre trial SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the European-Group-for-Blood-and-Morrow-Transplantation/22nd Meeting of the EBMT-Nures-Group/5th Meeting of the EMBT-Data-Management-Group CY MAR 19-22, 2006 CL Hamburg, GERMANY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Cologne, Cologne, Germany. Univ Calif Los Angeles, Los Angeles, CA USA. Duke Univ Hosp, Durham, NC USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Mainz, D-6500 Mainz, Germany. Silesian Med Univ, Katowice, Poland. Sahlgrenska Univ Hosp, Gothenburg, Sweden. Singapore Gen Hosp, Singapore 0316, Singapore. Hosp Santa Chiara, Pisa, Italy. NCI, Bethesda, MD 20892 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2006 VL 37 SU 1 BP S163 EP S163 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 028WT UT WOS:000236520200431 ER PT J AU Orchard, KH Cooper, M Lewington, V Tristam, M Zivanovic, M Thom, J Quadri, S Richardson, D Causer, L Johnson, P AF Orchard, KH Cooper, M Lewington, V Tristam, M Zivanovic, M Thom, J Quadri, S Richardson, D Causer, L Johnson, P TI Targeted radiotherapy in haematopoietic stem cell transplantation: results of a phase I trial using an Yttrium-90-labelled anti-CD66 murine monoclonal antibody demonstrating consistent BM targeting SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the European-Group-for-Blood-and-Morrow-Transplantation/22nd Meeting of the EBMT-Nures-Group/5th Meeting of the EMBT-Data-Management-Group CY MAR 19-22, 2006 CL Hamburg, GERMANY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 Southampton Univ Hosp, Southampton, Hants, England. St Bartholomews Hosp, London, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2006 VL 37 SU 1 BP S45 EP S46 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 028WT UT WOS:000236520200113 ER PT J AU Seggewiss, R Lore, K Guenaga, FJ Pittaluga, S Mattapallil, J Chow, C Ambrozak, D Bailer, RT Koup, RA Nason, MC Meier-Schellersheim, M Donahue, RE Hollander, GA Blazer, R Dunbar, CE Douek, DC AF Seggewiss, R Lore, K Guenaga, FJ Pittaluga, S Mattapallil, J Chow, C Ambrozak, D Bailer, RT Koup, RA Nason, MC Meier-Schellersheim, M Donahue, RE Hollander, GA Blazer, R Dunbar, CE Douek, DC TI Keratinocyte growth factor improves T-cell immune reconstitution in rhesus macaques after myeloablative autologous stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 32nd Annual Meeting of the European-Group-for-Blood-and-Morrow-Transplantation/22nd Meeting of the EBMT-Nures-Group/5th Meeting of the EMBT-Data-Management-Group CY MAR 19-22, 2006 CL Hamburg, GERMANY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp C1 NHLBI, NIH, DHHS, Bethesda, MD 20892 USA. NIAID, NIH, DHHS, Bethesda, MD 20892 USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. NIH, Ctr Clin, DHHS, Bethesda, MD 20892 USA. Univ Basel, Basel, Switzerland. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2006 VL 37 SU 1 BP S3 EP S3 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 028WT UT WOS:000236520200007 ER PT J AU Gerloff, C Bushara, K Sailer, A Wassermann, EM Chen, R Matsuoka, T Waldvogel, D Wittenberg, GF Ishii, K Cohen, LG Hallett, M AF Gerloff, C Bushara, K Sailer, A Wassermann, EM Chen, R Matsuoka, T Waldvogel, D Wittenberg, GF Ishii, K Cohen, LG Hallett, M TI Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke SO BRAIN LA English DT Review DE plasticity; stroke; recovery; motor control; motor cortex ID POSITRON-EMISSION-TOMOGRAPHY; SEQUENTIAL FINGER MOVEMENTS; FUNCTIONAL MRI; PREMOTOR CORTEX; CEREBRAL ACTIVATION; STRIATOCAPSULAR STROKE; POSTSTROKE HEMIPARESIS; COMPUTER INTERFACES; SUPPLEMENTARY MOTOR; CORTICAL ACTIVATION AB Clinical recovery after stroke can be significant and has been attributed to plastic reorganization and recruitment of novel areas previously not engaged in a given task. As equivocal results have been reported in studies using single imaging or electrophysiological methods, here we applied an integrative multimodal approach to a group of well-recovered chronic stroke patients (n = 11; aged 50-81 years) with left capsular lesions. Focal activation during recovered hand movements was assessed with EEG spectral analysis and (H2O)-O-15-PET with EMG monitoring, cortico-cortical connectivity with EEG coherence analysis (cortico-cortical coherence) and corticospinal connectivity with transcranial magnetic stimulation (TMS). As seen from comparisons with age-matched controls, our patients showed enhanced recruitment of the lateral premotor cortex of the lesioned hemisphere [Brodmann area (BA) 6], lateral premotor and to a lesser extent primary sensorimotor and parietal cortex of the contralesional hemisphere (CON-H; BA 4 and superior parietal lobule) and left cerebellum (patients versus controls, Z > 3.09). EEG coherence analysis showed that after stroke cortico-cortical connections were reduced in the stroke hemisphere but relatively increased in the CON-H (ANOVA, contrast analysis, P < 0.05), suggesting a shift of functional connectivity towards the CON-H. Nevertheless, fast conducting corticospinal transmission originated exclusively from the lesioned hemisphere. No direct ipsilateral motor evoked potentials (MEPs) could be elicited with TMS over the contralesional primary motor cortex (iM1) in stroke patients. We conclude that (i) effective recovery is based on enhanced utilization of ipsi- and contralesional resources, (ii) basic corticospinal commands arise from the lesioned hemisphere without recruitment of ('latent') uncrossed corticospinal tract fibres and (iii) increased contralesional activity probably facilitates control of recovered motor function by operating at a higher-order processing level, similar to but not identical with the extended network concerned with complex movements in healthy subjects. C1 Univ Tubingen, Sch Med, Dept Neurol, Cort Physiol Res Grp, Tubingen, Germany. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Cort Physiol Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Brain Simulat Unit, NIH, Bethesda, MD 20892 USA. RP Gerloff, C (reprint author), Univ Tubingen, Hertie Inst Clin Brain Res, Dept Gen Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM christian.gerloff@uni-tuebingen.de; hallettm@ninds.nih.gov RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 FU Intramural NIH HHS NR 126 TC 225 Z9 239 U1 1 U2 42 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2006 VL 129 BP 791 EP 808 DI 10.1093/brain/awh713 PN 3 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 013TY UT WOS:000235433800023 PM 16364955 ER PT J AU Novozhilov, AS Karev, GP Koonin, EV AF Novozhilov, Artem S. Karev, Georgy P. Koonin, Eugene V. TI Biological applications of the theory of birth-and-death processes SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE mathematical modeling; genome evolution; birth-and-death process; Moran model; horizontal gene transfer; tumorigenesis ID HORIZONTAL GENE-TRANSFER; TUMOR-SUPPRESSOR GENES; PURIFYING SELECTION; LARGE-SCALE; MOLECULAR PHYLOGENIES; MULTIGENE FAMILIES; QUASI-STATIONARITY; CANCER INITIATION; PROTEIN UNIVERSE; GENOME EVOLUTION AB In this review, we discuss applications of the theory of birth-and-death processes to problems in biology, primarily, those of evolutionary genomics. The mathematical principles of the theory of these processes are briefly described. Birth-and-death processes, with some straightforward additions such as innovation, are a simple, natural and formal framework for modeling a vast variety of biological processes such as population dynamics, speciation, genome evolution, including growth of paralogous gene families and horizontal gene transfer and somatic evolution of cancers. We further describe how empirical data, e.g. distributions of paralogous gene family size, can be used to choose the model that best reflects the actual course of evolution among different versions of birth-death-and-innovation models. We conclude that birth-and-death processes, thanks to their mathematical transparency, flexibility and relevance to fundamental biological processes, are going to be an indispensable mathematical tool for the burgeoning field of systems biology. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013 OI Novozhilov, Artem/0000-0001-5469-2557 NR 96 TC 48 Z9 48 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 EI 1477-4054 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD MAR PY 2006 VL 7 IS 1 BP 70 EP 85 DI 10.1093/bib/bbk006 PG 16 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 090DL UT WOS:000240930700006 PM 16761366 ER PT J AU Srinivasan, R Childs, R AF Srinivasan, R Childs, R TI Nephrotic syndrome following non-myeloablative stem cell transplantation - response to Ruiz-Arguelles and Gomez-Almaguer SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE stem cell transplantation C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Srinivasan, R (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM childsr@nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2006 VL 132 IS 6 BP 802 EP 903 DI 10.1111/j.1365-2141.2006.06000.x PG 3 WC Hematology SC Hematology GA 012HX UT WOS:000235330300023 ER PT J AU Houston, D Ohno, M Nicholas, RA Jacobson, KA Harden, TK AF Houston, D Ohno, M Nicholas, RA Jacobson, KA Harden, TK TI [P-32]2-iodo-N-6-methyl-(N)-methanocarba-2 '-deoxyadenosine-3 ',5 '-bisphosphate ([P-32]MRS2500), a novel radioligand for quantification of native P2Y(1) receptors SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE P2Y(1) receptor; competitive antagonist; radioligand; MRS2500; MRS2279 ID MUTATIONAL ANALYSIS; BIOLOGICAL-ACTIVITY; ADP RECEPTORS; RAT; ANTAGONISTS; AGONIST; CLONING; ANALOGS; ATP; CONFORMATION AB 1 Analysis of the P2Y family of nucleotide-activated G-protein-coupled receptors has been compromised by the lack of selective high-affinity, high-specific-radioactivity radioligands. We have pursued quantification of the P2Y(1) receptor through the development of a series of selective P2Y(1) receptor antagonists. 2 Recently, we synthesized 2-iodo-N-6-methyl-(N)- methanocarba-2'-deoxyadenosine 3',5'-bisphosphate (MRS2500), a selective, competitive antagonist that exhibits a K-i of 0.8 nM in competition-binding assays with [H-3] MRS2279. A 3'- monophosphate precursor molecule, MRS2608, was radiolabeled at the 5' position with P-32 using polynucleotide kinase and [gamma P-32] ATP to yield [P-32] MRS2500. 3 [P-32] MRS2500 bound selectively to Sf9 insect cell membranes expressing the human P2Y(1) receptor (Sf9-P2Y(1)), but did not detectably bind membranes expressing other P2Y receptors. P2Y(1) receptor binding to [P-32] MRS2500 was saturable with a K-D of 1.2 nM. Agonists and antagonists of the P2Y(1) receptor inhibited [P-32] MRS2500 binding in Sf9-P2Y(1) membranes with values in agreement with those observed in functional assays of the P2Y(1) receptor. 4 A high-affinity binding site for [P-32] MRS2500 (K-D 0.33 nM) was identified in rat brain, which exhibited the pharmacological selectivity of the P2Y(1) receptor. Distribution of this binding site varied among rat tissues, with the highest amount of binding appearing in lung, liver, and brain. Among brain regions, distribution of the [P-32] MRS2500 binding site varied by six-fold, with the highest and lowest amounts of sites detected in cerebellum and cortex, respectively. 5 Taken together, these data illustrate the synthesis and characterization of a novel P2Y(1) receptor radioligand and its utility for examining P2Y(1) receptor expression in native mammalian tissues. C1 Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NIDDKD, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. RP Houston, D (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, CB 7365, Chapel Hill, NC 27599 USA. EM dhouston@med.unc.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20]; NHLBI NIH HHS [R01 HL054889, HL54889, R01 HL071131, R29 HL054889]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 42 TC 25 Z9 26 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 2006 VL 147 IS 5 BP 459 EP 467 DI 10.1038/sj.bjp.0706453 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 024BP UT WOS:000236170200001 PM 16299552 ER PT J AU Jia, L Noker, PE Coward, L Gorman, GS Protopopova, M Tomaszewski, JE AF Jia, L Noker, PE Coward, L Gorman, GS Protopopova, M Tomaszewski, JE TI Interspecies pharmacokinetics and in vitro metabolism of SQ109 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE antituberculosis; diamine; SQ109; ADME; pharmacokinetics ID COMBINATORIAL LEAD OPTIMIZATION; EQUILIBRIUM DIALYSIS; TICLOPIDINE; ETHAMBUTOL; CYP2C19; TUBERCULOSIS; INHIBITION; PHENYTOIN; ANIMALS; BINDING AB 1 This study aimed at characterizing the interspecies absorption, distribution, metabolism and elimination (ADME) profile of N-geranyl-N'-(2-adamantyl) ethane-1,2-diamine (SQ109), a new diamine-based antitubercular drug. 2 Single doses of SQ109 were administered ( intravenously (i.v.) and per os ( p. o.)) to rodents and dogs and blood samples were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS). Based on i.v. equivalent body surface area dose, the terminal half-life (t(1/2)) of SQ109 in dogs was longer than that in rodents, reflected by a larger volume of distribution (V-ss) and a higher clearance rate of SQ109 in dogs, compared to that in rodents. The oral bioavailability of SQ109 in dogs, rats and mice were 2.4 - 5, 12 and3.8%, respectively. 3 After oral administration of [C-14] SQ109 to rats, the highest level of radioactivity was in the liver, followed by the lung, spleen and kidney. Tissue-to-blood ratios of [C-14] SQ109 were greater than 1. Fecal elimination of [C-14] SQ109 accounted for 22.2% of the total dose of [C-14] SQ109, while urinary excretion accounted for only 5.6%. The binding of [C-14] SQ109 (0.1 - 2.5 mu g ml(-1)) to plasma proteins varied from 6 to 23% depending on the species ( human, mouse, rat and dog). 4 SQ109 was metabolized by rat, mouse, dog and human liver microsomes, resulting in 22.8, 48.4, 50.8 or 58.3%, respectively, of SQ109 remaining after a 10-min incubation at 37 degrees C. The predominant metabolites in the human liver microsomes gave intense ion signals at 195, 347 and 363 m/z, suggesting the oxidation, epoxidation and N-dealkylation of SQ109. P450 reaction phenotyping using recombinant cDNA-expressedhuman CYPs in conjunction with specific CYP inhibitors indicated that CYP2D6 and CYP2C19 were the predominant CYPs involved in SQ109 metabolism. C1 NCI, Dev Therapeut Program, NIH, Rockville, MD 20852 USA. So Res Inst, Birmingham, AL 35255 USA. Sequella Inc, Rockville, MD USA. RP Jia, L (reprint author), NCI, Dev Therapeut Program, NIH, 6130 Execut Blvd,Rm 8042, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU NCI NIH HHS [N01-CM-52203, N01CM52203, N01-CM-07110] NR 30 TC 66 Z9 75 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 2006 VL 147 IS 5 BP 476 EP 485 DI 10.1038/sj.bjp.0706650 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 024BP UT WOS:000236170200003 PM 16432511 ER PT J AU Saidak, Z Blake-Palmer, K Hay, DL Northup, JK Glass, M AF Saidak, Z Blake-Palmer, K Hay, DL Northup, JK Glass, M TI Differential activation of G-proteins by mu-opioid receptor agonists SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE opioid; G-protein; MOR; agonist selectivity of G-proteins; inverse agonist; analgesia ID BETA-GAMMA-SUBUNIT; ALPHA-SUBUNIT; SUPRASPINAL ANALGESIA; RAT THALAMUS; K+ CHANNELS; BINDING; CELLS; EFFICACY; MYRISTOYLATION; RECONSTITUTION AB 1 We investigated the ability of the activated mu-opioid receptor (MOR) to differentiate between myristoylated G(alpha i1) and G(alpha oA) type G(alpha) proteins, and the maximal activity of a range of synthetic and endogenous agonists to activate each G(alpha) protein. 2 Membranes from HEK293 cells stably expressing transfected MOR were chaotrope extracted to denature endogenous G-proteins and reconstituted with specific purified G-proteins. The G(alpha) subunits were generated in bacteria and were demonstrated to be recognised equivalently to bovine brain purified G(alpha) protein by CB1 cannabinoid receptors. The ability of agonists to catalyse the MOR-dependent GDP/[S-35] GTP(gamma)S exchange was then compared for G(alpha i1) and G(alpha oA). 3 Activation of MOR by DAMGO produced a high-affinity saturable interaction for G(alpha oA) (K-m = 20 +/- 1 nM) but a low-affinity interaction with G(alpha i1) (K-m = 116 +/- 12 nM). DAMGO, metenkephalin and leucine-enkephalin displayed maximal G(alpha) activation among the agonists evaluated. Endomorphins 1 and 2, methadone and beta-endorphin activated both G(alpha) to more than 75% of the maximal response, whereas fentanyl partially activated both G-proteins. 4 Buprenorphine and morphine demonstrated a statistically significant difference between the maximal activities between G(alpha i1) and G(alpha oA). Interestingly, DAMGO, morphine, endomorphins 1 and 2, displayed significant differences in the potencies for the activation of the two G(alpha). Differences in maximal activity and potency, for G(alpha i1) versus G(alpha oA), are both indicative of agonist selective activation of G-proteins in response to MOR activation. 5 These findings may provide a starting point for the design of drugs that demonstrate greater selectivity between these two G-proteins and therefore produce a more limited range of effects. C1 Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, Auckland 1, New Zealand. Univ Auckland, Liggins Inst, Auckland 1, New Zealand. Univ Auckland, Sch Biol Sci, Auckland 1, New Zealand. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Glass, M (reprint author), Univ Auckland, Fac Med & Hlth Sci, Dept Pharmacol & Clin Pharmacol, Private Bag 92019, Auckland 1, New Zealand. EM m.glass@auckland.ac.nz RI Hay, Debbie/D-4441-2009 NR 52 TC 38 Z9 40 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 2006 VL 147 IS 6 BP 671 EP 680 DI 10.1038/sj.bjp.0706661 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 029AX UT WOS:000236531300011 PM 16415903 ER PT J AU Wakefield, JC Kirk, SA Pottick, KJ Hsieh, DK Tian, X AF Wakefield, JC Kirk, SA Pottick, KJ Hsieh, DK Tian, X TI The lay concept of conduct disorder: Do nonprofessionals use syndromal symptoms or internal dysfunction to distinguish disorder from delinquency? SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE conduct disorder; diagnosis; harmful dysfunction; philosophy; mental disorder; diagnosis and classification; models or theories of psychiatry; adolescents; child psychiatry; false positives ID MENTAL-DISORDER; HARMFUL DYSFUNCTION; CLINICAL-SIGNIFICANCE; ANTISOCIAL-BEHAVIOR; SOCIAL-CONTEXT; PUERTO-RICO; SERVICE USE; IMPAIRMENT; PREVALENCE; EVOLUTIONARY AB Background: Conduct disorder (CD) must be distinguished from nondisordered delinquent behaviour to avoid false positives, especially when diagnosing youth from difficult environments. However, the nature of this distinction remains controversial. The DSM-IV observes that its own syndromal CD diagnostic criteria conflict with its definition of mental disorder, which requires that symptoms be considered a manifestation of internal dysfunction to warrant disorder diagnosis. Previous research indicates that professional judgments tend to be guided by the dysfunction requirement, not syndromal symptoms alone. However, there are almost no data on lay conceptualizations. Thus it remains unknown whether judgments about CD are anchored in a broadly shared understanding of mental disorder that provides a basis for professional-lay consensus. Objective: The present study tests which conception of CD, syndromal-symptoms or dysfunction-requirement, corresponds most closely to lay judgments of disorder or nondisorder and compares lay and professional judgments. We hypothesized that lay disorder judgments, like professional judgments, tend to presuppose the dysfunction requirement. Method: Three lay samples (nonclinical social workers, nonpsychiatric nurses, and undergraduates) rated their agreement that youths described in clinical vignettes have a mental disorder. All vignettes satisfied DSM-IV CD diagnostic criteria. Vignettes were varied to present syndromal symptoms only, symptoms suggesting internal dysfunction, and symptoms resulting from reactions to negative circumstances, without dysfunction. Results: All lay samples attributed disorder more often to youths whose symptoms suggested internal dysfunction than to youths with similar symptoms but without a likely dysfunction. Conclusions: The dysfunction requirement appears to reflect a widely shared lay and professional concept of disorder. C1 NYU, Sch Social Work, New York, NY 10031 USA. Univ Calif Los Angeles, Sch Publ Affairs, Dept Social Welf, Los Angeles, CA 90024 USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA. Los Angeles Cty Dept Mental Hlth, Psychiat Mobile Response Team, Los Angeles, CA USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Wakefield, JC (reprint author), 309 W 104 St 9C, New York, NY 10025 USA. EM jw111@nyu.edu FU NIMH NIH HHS [R01 MH-43450] NR 26 TC 12 Z9 12 U1 1 U2 3 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD MAR PY 2006 VL 51 IS 4 BP 210 EP 217 PG 8 WC Psychiatry SC Psychiatry GA 025LO UT WOS:000236267800002 PM 16629345 ER PT J AU Ibrahim, R Frederickson, H Parr, A Ward, Y Moncur, J Khleif, SN AF Ibrahim, R Frederickson, H Parr, A Ward, Y Moncur, J Khleif, SN TI Expression of FasL in squamous cell carcinomas of the cervix and cervical intraepithelial neoplasia and its role in tumor escape mechanism SO CANCER LA English DT Article DE FasL; CD95L; tumor escape mechanisms; cervical carcinoma; immuno-histochemistry; Fas/FasL ID CYTOTOXIC T-LYMPHOCYTES; APO-1/CD95 LIGAND; CANCER-CELLS; IMMUNE PRIVILEGE; IN-VIVO; APOPTOSIS; COUNTERATTACK; ADENOCARCINOMAS; MICROVESICLES; ANTIGENS AB BACKGROUND. To date, several mechanisms have been described by which malignant cells escape from the immune system. One of these is through the expression of FasL. The authors hypothesized that the Fas/FasL interaction enables cervical carcinoma cells to induce apoptosis of the cells of the immune system and thereby escape from them. METHODS. The authors tested the expression of FASL on the Surface of cervical carcinoma tissues. Next, they stained the same cervical tissues with anti-human leukocyte common antigen and TUNEL to identify, apoptotic cells. All in vitro functional assay was then done to test if the FASL expressed oil the surface of cervical carcinoma cell lines was or was not responsible for inducing apoptosis in T-cells. Finally, they compared the expression of FASL on normal and dysplastic cervical tissues. RESULTS. Ninety-four percent of the cervical carcinoma tissues the authors tested expressed FasL and the majority of the apoptotic cells in the specimens were leukocytes with very few tumor cells. In the in vitro functional assay, only the Fasl expressing cell line and not the Fasl negative cell line was able to induce apoptosis of the Fas-expressing Jurkat cells. On examining the normal cervical tissues, the authors found that the expression of Fasl was confined to the basal cell layer with loss of expression observed in the suprabasal layers, which made it an immune privileged site. Conversely, there was persistent expression of Fast, in the dysplastic layers in cervical dysplasia and squamous cell carcinoma specimens. CONCLUSIONS. The findings of the current study support the authors' hypothesis that persistent expression of Fast, plays a role in the ability of cervical carcinoma cells to escape from the immune system. C1 NCI, Ctr Canc Res, Natl Naval Med Ctr, Canc Vaccine Branch,NIH, Bethesda, MD 20889 USA. NCI, Ctr Canc Res, Canc Therapeut Branch, Bethesda, MD 20889 USA. NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. RP Khleif, SN (reprint author), NCI, Ctr Canc Res, Natl Naval Med Ctr, Canc Vaccine Branch,NIH, 8901 Wisconsin Ave,Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM khleif@nih.gov NR 33 TC 15 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2006 VL 106 IS 5 BP 1065 EP 1077 DI 10.1002/cncr.21697 PG 13 WC Oncology SC Oncology GA 019GD UT WOS:000235822700012 PM 16456813 ER PT J AU Ahlers, CM Figg, WD AF Ahlers, CM Figg, WD TI ETS-TMPRSS2 fusion gene products in prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE prostate cancer; chromosomal rearrangement; fusion gene; ETS; carcinogenesis; carcinoma; TMPRSS2 ID SERINE-PROTEASE; EXPRESSION; CARCINOMA; TMPRSS2; CLONING AB Genes playing a role in carcinogenesis have often been identified through analysis of recurrent chromosomal rearrangements. Although such rearrangements are well known in leukemias, lymphomas, and sarcomas, they have not been well characterized in carcinomas. In the October 28, 2005 issue of Science, a study by Tomlins et al. usesbioinformatics techniques to identify candidate oncogenic chromosomal changes based on analysis of outlier gene expression. The authors determined that two ETS transcription factors, ERG and ETV1 were outliers in prostate cancer. The group reports recurrent fusions of the 5' untranslated region of the TMPRSS2 gene to ERG and ETV1 in the majority of prostate cancer samples containing the outlier expression. In cell lines containing the fusion gene, androgen appears to play a role in mediating ETS overexpression. This fusion gene product may play an important role in the development, diagnosis, and treatment of prostate cancer. C1 NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 15 TC 13 Z9 13 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2006 VL 5 IS 3 BP 254 EP 255 PG 2 WC Oncology SC Oncology GA 043NU UT WOS:000237608800009 PM 16575200 ER PT J AU Kaphingst, KA Zanfini, CJ Emmons, KM AF Kaphingst, KA Zanfini, CJ Emmons, KM TI Accessibility of web sites containing colorectal cancer information to adults with limited literacy (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE literacy; internet; cancer ID WORLD-WIDE-WEB; HEALTH INTERVIEW SURVEY; SCREENING-TESTS; READABILITY; INTERNET; QUALITY; EDUCATION; KNOWLEDGE; CONSUMERS; RISK AB The Internet could be a key channel for disseminating information about colorectal cancer (CRC) screening. Little research, however, has systematically examined factors other than writing style related to the reading difficulty of cancer information on the Internet. In the present study we assessed the reading difficulty of 19 CRC Web sites. We assessed pages within selected sites containing information on CRC screening or prevention using the SMOG readability formula and Suitability Assessment of Materials instrument. The average SMOG reading grade level was 12.8. The SAM results indicated common problems with the sites, including (1) lack of review of key ideas; (2) insufficient use of illustrations for key messages; (3) crowded layout and long line lengths; (4) small type size and lack of cues to highlight key content; and (5) lack of interactive features. Many Web sites providing CRC information may be too difficult for the average American adult and much too difficult for adults with limited literacy. The unique features of the Internet that could support learning are not being utilized. The Internet could be a powerful tool for educating individuals about CRC, but the barrier of difficult content must be addressed along with access barriers. C1 NHGRI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Ctr Community Baseds Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Amer Heart Assoc, Williston, VT 05495 USA. RP Kaphingst, KA (reprint author), NHGRI, Bldg 31,Room B2B37,31 Ctr Dr,MSC 2030, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU NCI NIH HHS [5R01CA098864] NR 36 TC 34 Z9 35 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2006 VL 17 IS 2 BP 147 EP 151 DI 10.1007/s10552-005-5116-3 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 004LO UT WOS:000234754500003 PM 16425092 ER PT J AU Chan, JM Holick, CN Leitzmann, MF Rimm, EB Willett, WC Stampfer, MJ Giovannucci, EL AF Chan, JM Holick, CN Leitzmann, MF Rimm, EB Willett, WC Stampfer, MJ Giovannucci, EL TI Diet after diagnosis and the risk of prostate cancer progression, recurrence, and death (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE diet; epidemiology; progression; prostate cancer; survivors ID FOOD FREQUENCY QUESTIONNAIRE; GROWTH-FACTOR-I; RANDOMIZED CLINICAL-TRIAL; RADICAL PROSTATECTOMY; DAIRY-PRODUCTS; FATTY-ACIDS; TOMATO PRODUCTS; EICOSAPENTAENOIC ACID; NATURAL-HISTORY; ANTIGEN ERA AB Objectives We examined post-diagnostic diet and risk of cancer progression in a cohort of men with prostate cancer from the Health Professionals Follow-up Study. Methods We observed 392 progression outcomes among 1,202 men diagnosed with incident localized/regional prostate cancer between 1986 and 1996. Men completed prospective dietary surveys before and after diagnosis and were followed through 2000. We examined post-diagnostic consumption of red meat, grains, vegetables, fruits, milk, tomatoes, tomato sauce, and fish as predictors of progression using Cox proportional hazard regression models adjusted for total energy, age, clinical factors, and pre-diagnostic diet. Results Men in the highest versus lowest quartile of post-diagnostic fish consumption had a multivariate hazard ratio (HR) of progression of 0.73 (95% CI 0.52-1.02); the comparable HR for tomato sauce was 0.56 (95% CI 0.38-0.82). We observed inverse linear relationships for fish and tomato sauce and risk of progression (HR = 0.83, p-value = 0.006 and HR = 0.80, p-value = 0.04 for a two serving/week increase of fish and tomato sauce, respectively). Milk and fresh tomato consumption were associated with small elevations in risk. Conclusions These data suggest that diet after diagnosis may influence the clinical course of prostate cancer, and fish and tomato sauce may offer some protection against disease progression. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Chan, JM (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, Room A622, San Francisco, CA 94143 USA. EM june@uorg.ucsf.edu FU NCI NIH HHS [5T 32 CA 09001-26, CA 55075, P50 CA89520]; NHLBI NIH HHS [HL 35464]; NIDDK NIH HHS [P30 DK040561-11] NR 44 TC 81 Z9 83 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2006 VL 17 IS 2 BP 199 EP 208 DI 10.1007/s10552-005-0413-4 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 004LO UT WOS:000234754500009 PM 16425098 ER PT J AU Milstien, S Spiegel, S AF Milstien, S Spiegel, S TI Targeting sphingosine-1-phosphate: A novel avenue for cancer therapeutics SO CANCER CELL LA English DT Editorial Material ID SPHINGOSINE KINASE; RECEPTOR; EDG-1 C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Milstien, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu NR 8 TC 84 Z9 85 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2006 VL 9 IS 3 BP 148 EP 150 DI 10.1016/j.ccr.2006.02.025 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 026YD UT WOS:000236378500002 PM 16530698 ER PT J AU Yanaihara, N Caplen, N Bowman, E Seike, M Kumamoto, K Yi, M Stephens, RM Okamoto, A Yokota, J Tanaka, T Colin, GA Liu, CG Croce, CM Harris, CC AF Yanaihara, N Caplen, N Bowman, E Seike, M Kumamoto, K Yi, M Stephens, RM Okamoto, A Yokota, J Tanaka, T Colin, GA Liu, CG Croce, CM Harris, CC TI Unique microRNA molecular profiles in lung cancer diagnosis and prognosis SO CANCER CELL LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CAENORHABDITIS-ELEGANS/; REDUCED EXPRESSION; HOST GENES; RNA; TARGETS; IDENTIFICATION; ACCUMULATION; PROGRESSION; SIGNATURE AB MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate miRNA's involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues as well as molecular signatures that differ in tumor histology. miRNA expression profiles correlated with survival of lung adenocarcinomas, including those classified as disease stage 1. High hsa-mir-155 and low hsa-let-7a-2 expression correlated with poor survival by univariate analysis as well as multivariate analysis for hsa-mir-155. The miRNA expression signature on outcome was confirmed by real-time RT-PCR analysis of precursor miRNAs and crossvalidated with an independent set of adenocarcinomas. These results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer. C1 NCI, Human Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Gene Silencing Sect, Off Sci & Technol Partnership, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI Frederick, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. Jikei Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 1058461, Japan. Natl Canc Ctr, Inst Res, Div Biol, Tokyo 1040045, Japan. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS; NCI NIH HHS [CA76259, N01-CO-12400] NR 48 TC 1852 Z9 2013 U1 40 U2 271 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2006 VL 9 IS 3 BP 189 EP 198 DI 10.1016/j.ccr.2006.01.025 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 026YD UT WOS:000236378500007 PM 16530703 ER PT J AU Acharya, MR Sparreboom, A Sausville, EA Conley, BA Doroshow, JH Venitz, J Figg, WD AF Acharya, MR Sparreboom, A Sausville, EA Conley, BA Doroshow, JH Venitz, J Figg, WD TI Interspecies differences in plasma protein binding of MS-275, a novel histone deacetylase inhibitor SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE MS-275; histone deacetylase inhibitor; protein binding; equilibrium dialysis ID CANCER AB MS-275 (MS-27- 275; 3-pyridylmethyl-N-{4[(2-aminophenyl)-carbamoyl]-benzyl-carbamate) is a histone deacetylase inhibitor under clinical development as an anticancer agent. Here, we examined the role of protein binding as a possible determinant of the pharmacokinetic behavior of MS-275. The distribution of MS-275 in plasma was studied in vitro using equilibrium dialysis and ex vivo in five cancer patients receiving the drug orally at a dose of 10 mg/m(2). The dialysis method uses a tracer amount of [G-H-3]MS-275 on a 96-well microdialysis plate with a 5-kDa cut-off membrane, and requires 250 mu l sample. The time to equilibrium was established to be within 5 h, and the mean unbound fraction of MS-275 (f(u)) over a presumed therapeutic concentration range in healthy volunteer human plasma was 0.188 +/- 0.0075 as compared to 0.168 +/- 0.0144 in cancer patients. The binding was concentration-independent, indicating a low affinity, possibly non-specific and non-saturable process. MS-275 was found to bind in decreasing order to plasma > alpha(1)-acid glycoprotein > albumin. Among 19 tested drugs, a slightly increased fu was observed in the presence of only ibuprofen (f(u), 0.236 +/- 0.001) and metoclopramide (f(u), 0.270 +/- 0.042), suggesting weakly competitive displacement from protein-binding sites (P < 0.01). Compared to humans, f(u) was significantly higher in plasma from mouse (0.376), rat (0.393), rabbit (0.355), dog (0.436), and pig (0.439) (P < 0.01), which may explain, in part, the species-dependent pharmacokinetic pro. le of MS-275 observed previously. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Sch Pharm, Richmond, VA 23298 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01,MSC1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 18 TC 22 Z9 22 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2006 VL 57 IS 3 BP 275 EP 281 DI 10.1007/s00280-005-0058-8 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 996US UT WOS:000234201200001 PM 16028097 ER PT J AU Chearwae, W Wu, CP Chu, HY Lee, TR Ambudkar, SV Limtrakul, P AF Chearwae, W Wu, CP Chu, HY Lee, TR Ambudkar, SV Limtrakul, P TI Curcuminoids purified from turmeric powder modulate the function of human multidrug resistance protein 1 (ABCC1) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE curcumin I; curcumin II; curcumin III; modulator; multidrug resistance (MDR); multidrug resistance related protein (MRP1) ID HUMAN P-GLYCOPROTEIN; ATP HYDROLYSIS; CURCUMA-LONGA; TRANSPORTERS; CANCER; CELLS; ANTIOXIDANT; MECHANISM; STATE AB Multidrug resistance is a major cause of chemotherapy failure in cancer patients. One of the resistance mechanisms is the overexpression of drug efflux pumps such as P-glycoprotein and multidrug resistance protein 1 (MRP1, (ABCC1)). In this study, curcumin mixture and three major curcuminoids purified from turmeric ( curcumin I, II, and III) were tested for their ability to modulate the function of MRP1 using HEK293 cells stably transfected with MRP1-pcDNA3.1 and pcDNA3.1 vector alone. The IC50 of curcuminoids in these cell lines ranged from 14.5-39.3 mu M. Upon treating the cells with etoposide in the presence of 10 mu M curcuminoids, the sensitivity of etoposide was increased by several folds only in MRP1 expressing and not in pcDNA3.1-HEK 293 cells. Western blot analysis showed that the total cellular level of MRP1 protein level was not affected by treatment with 10 mu M curcuminoids for three days. The modulatory effect of curcuminoids on MRP1 function was confirmed by the inhibition of efflux of two fluorescent substrates, calcein-AM and fluo4-AM. Although all the three curcuminoids increased the accumulation of fluorescent substrates in a concentration-dependent manner, curcumin I was the most effective inhibitor. In addition, curcuminoids did not affect 8-azido[alpha-P-32] ATP binding, however they did stimulate the basal ATPase activity and inhibited the quercetin-stimulated ATP hydrolysis of MRP1 indicating that these bioflavonoids interact most likely at the substrate-binding site(s). In summary, these results demonstrate that curcuminoids effectively inhibit MRP1-mediated transport and among curcuminoids, curcumin I, a major constituent of curcumin mixture, is the best modulator. C1 Chiang Mai Univ, Fac Med, Dept Biochem, Chiang Mai 50200, Thailand. NCI, Cell Biol Lab, Ctr Canc Res, DHHS,NIH, Bethesda, MD 20892 USA. Univ Houston, Dept Chem, Houston, TX 77204 USA. RP Limtrakul, P (reprint author), Chiang Mai Univ, Fac Med, Dept Biochem, Chiang Mai 50200, Thailand. EM ambudkar@mail.nih.gov; plimtrak@mail.med.cmu.ac.th RI Ambudkar, Suresh/B-5964-2008; OI Lee, T. Randall/0000-0001-9584-8861 NR 26 TC 60 Z9 68 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2006 VL 57 IS 3 BP 376 EP 388 DI 10.1007/s00280-005-0052-1 PG 13 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 996US UT WOS:000234201200014 PM 16021489 ER PT J AU Vernon, SW Meissner, HI Miller, SM AF Vernon, SW Meissner, HI Miller, SM TI The role of behavioral science in cancer prevention research: Planning the next steps in the collaborative process SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Univ Texas, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77030 USA. NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. RP Vernon, SW (reprint author), Univ Texas, Sch Publ Hlth, Div Hlth Promot & Behav Sci, 7000 Fannin, Houston, TX 77030 USA. EM Sally.W.Vernon@uth.tmc.edu NR 9 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2006 VL 15 IS 3 BP 413 EP 415 DI 10.1158/1055-9965.EPI-06-0103 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 024AV UT WOS:000236168200001 PM 16537691 ER PT J AU Sansbury, LB Bergen, AW Wanke, KL Yu, BB Caporaso, NE Chatterjee, N Ratnasinghe, L Schatzkin, A Lehman, TA Kalidindi, A Modali, R Lanza, E AF Sansbury, LB Bergen, AW Wanke, KL Yu, BB Caporaso, NE Chatterjee, N Ratnasinghe, L Schatzkin, A Lehman, TA Kalidindi, A Modali, R Lanza, E TI Inflammatory cytokine gene polymorphisms, nonsteroidal anti-inflammatory drug use, and risk of adenoma polyp recurrence in the polyp prevention trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INTERLEUKIN-10 PROMOTER POLYMORPHISM; HUMAN COLON-CANCER; COLORECTAL-CANCER; CYCLOOXYGENASE-2 EXPRESSION; ALZHEIMERS-DISEASE; ONLINE DATABASES; RANDOMIZED-TRIAL; BOWEL-DISEASE; ASPIRIN; CARCINOMA AB Background: Pro- and anti-inflammatory cytokine genes may be important in the maintenance and progression of colorectal cancer. It is possible that single-nucleotide polymorphisms in inflammatory genes may play a role in chronic colonic inflammation and development of colorectal adenomas. Furthermore, common variants in cytokine genes may modify the anti-inflammatory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the prevention of colorectal cancer. Methods: We examined the association between cytokine gene polymorphisms and risk of recurrent adenomas among 1,723 participants in the Polyp Prevention Trial. We used logistic regression to calculate odds ratios (OR) for the association between genotype, NSAID use, and risk of adenoma recurrence. Results: Cytokine gene polymorphisms were not statistically significantly associated with risk of adenoma recurrence in our study. We observed statistically significant interaction, between NSAID use, IL-10 -1082 G > A genotype, and risk of adenoma recurrence (P = 0.01) and multiple adenoma recurrence (P = 0.01). Carriers of the IL-10 -1082 G > A variant allele who were non-NSAID users had a statistically significant decreased risk of multiple adenoma recurrend (OR, 0.43; 95% confidence interval, 0.24-0.77) as well as nonsignificant 30% decreased risk of any adenoma recurrence. In contrast, NSAID users who were carriers of the IL-1.0 -1082 G > A variant allele were at an increased risk of any adenoma recurrence (OR, 1.55; 95% confidence interval 1.00-2.43). Conclusion: These findings suggest that individuals who are carriers of the IL-10 -1082 G > A variant allele may no benefit from the chemoprotective effect of NSAIDs or adenoma polyp recurrence. C1 NCI, Ctr Canc Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Canc Prevent Fellowship Program, NIH, Bethesda, MD USA. NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, NIH, Bethesda, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD USA. Nalt Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR USA. Univ Arkansas Med Sci, Coll Med, Dept Surg, Little Rock, AR USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Laurel, MD USA. BioServe Biotechnol Ltd, Laurel, MD USA. RP Sansbury, LB (reprint author), NCI, Ctr Canc Res, Dept Hlth & Human Serv, NIH, Suite 702,6116 Executive Blvd,MSC 8235, Bethesda, MD 20892 USA. EM sansburl@mail.nih.gov OI Bergen, Andrew/0000-0002-1237-7644 FU Intramural NIH HHS NR 60 TC 17 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2006 VL 15 IS 3 BP 494 EP 501 DI 10.1158/1055-9965.EPI-05-0763 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 024AV UT WOS:000236168200017 PM 16537707 ER PT J AU Lubin, JH Caporaso, NE AF Lubin, JH Caporaso, NE TI Cigarette smoking and lung cancer: Modeling total exposure and intensity SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DOSE-RESPONSE RELATIONSHIP; TOBACCO-RELATED CANCERS; DNA-REPAIR CAPACITY; EXCISION-REPAIR; RISK; SUSCEPTIBILITY; CARCINOGEN; SMOKERS; METABOLITES; ADDUCTS AB Investigators typically analyze cigarette smoking using smoking duration and intensity (number of cigarettes smoked per day) as risk factors. However, odds ratios (OR) for categories If intensity either adjusted for, or jointly with, duration of smoking may be distorted by differences in total pack-years of exposure to cigarette smoke. To study effects of intensity, we apply a linear excess OR model to compare total exposure delivered at low intensity for a long period of time with an equal total exposure delivered at high intensity for a short period of time to data from a large case-control study of lung cancer. The excess OR per pack-year increases with intensity :or subjects who smoke <= 20 cigarettes per day and decreases with intensity for subjects who smoke > 20 cigarettes per day. The intensity patterns are homogeneous by histologic type of lung cancer, suggesting that observed differences in risks by histologic type are related to total smoking exposure or smoking duration and not smoking intensity. At lower smoking intensifies, there is an "exposure enhancement" effect such that for equal total exposure, the excess OR per pack-year increases with intensity. At higher smoking intensities, there is a "reduced potency" or "wasted exposure" effect such that for equal total exposure, the excess OR per pack-year decreases with intensity (i.e., smoking at a lower intensity for longer duration is more deleterious than smoking at a higher intensity for shorter duration). C1 NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Rockville, MD 20852 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Execut Blvd, Rockville, MD 20852 USA. EM lubinj@mail.nih.gov NR 29 TC 77 Z9 81 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2006 VL 15 IS 3 BP 517 EP 523 DI 10.1158/1055-9965.EPI-05-0863 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 024AV UT WOS:000236168200020 PM 16537710 ER PT J AU Garcia-Closas, M Malats, N Real, FX Welch, R Kogevinas, M Chatterjee, N Pfeiffer, R Silverman, D Dosemeci, M Tardon, A Serra, C Carrato, A Garcia-Closas, R Castano-Vinyals, G Chanock, S Yeager, M Rothman, N AF Garcia-Closas, M Malats, N Real, FX Welch, R Kogevinas, M Chatterjee, N Pfeiffer, R Silverman, D Dosemeci, M Tardon, A Serra, C Carrato, A Garcia-Closas, R Castano-Vinyals, G Chanock, S Yeager, M Rothman, N TI Genetic variation in the nucleoticle excision repair pathway and bladder cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID WHITE BLOOD-CELLS; DNA-REPAIR; POLYMORPHISMS; GENOTYPES; XPD; ASSOCIATION; ASSAY AB Nucleotide excision repair (NER) is critical for protecting against damage from carcinogens in tobacco smoke. We evaluated the influence of common genetic variation in the NER pathway on bladder cancer risk by analyzing 22 single nucleotide polymorphisms (SNP) in seven NER genes (XPC, RAD23B, 1RCCI, ERCC2, ERCC4, ERCC5, and ERCC6). Our study population included 1,150 patients with transitional cell carcinoma of the urinary bladder and 1,149 control subjects from Spain. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, and smoking status. Subjects with the variant genotypes for SNPs in four of the seven genes evaluated had small increases in bladder cancer risk compared to subjects with the homozygous wild-type genotypes: RAD23B IVS5-15A > G (OR, 1.3; 95% CI, 1.1-1.5; P = 0.01), ERCC2 R156R (OR, 1.3; 95% Cl, 1.1-1.6; P = 0.006), ERCC1 IVS5+33A > C (OR, 1.2; 95% CI, 1.0-1.5; P = 0.06; P-trend = 0.04), and ERCC5 M254V (OR, 1.4 95% CI, 1.0-2.0; P = 0.04). A global test for pathway effects indicated that genetic variation in NER characterized by the 22 SNPs analyzed in this study significantly predicts bladder cancer risk (P = 0.04). Pairwise comparisons suggested that carrying variants in two genes could result in substantial increases in risk. Classification tree analyses suggested the presence of subgroups of individuals defined by smoking and NER genotypes that could have substantial increases in risk. In conclusion, these findings provided support for the influence of genetic variation in NER or bladder cancer risk. A detailed characterization of genetic variation in key NER genes is warranted and might ultimately help identify multiple susceptibility variants that could be responsible for substantial joint increases in risk. C1 NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, NIH,Core Genotype Facil Adv Technol Ctr,Dept Hlth, Rockville, MD 20852 USA. Univ Pompeu Fabra, Div Canc Epidemiol & Genet, Barcelona, Spain. Univ Pompeu Fabra, Inst Municipal Invest Med, Barcelona, Spain. Univ Oviedo, Oviedo, Spain. Consorci Hosp Parc Tauli, Sabadell, Spain. Hosp Univ Elche, Elche, Spain. Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain. RP Garcia-Closas, R (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, NIH,Core Genotype Facil Adv Technol Ctr,Dept Hlth, Room 7076,6120 Execut Blvd, Rockville, MD 20852 USA. EM montse@nih.gov RI Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat /0000-0003-1033-2650; FU Intramural NIH HHS NR 22 TC 104 Z9 111 U1 1 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2006 VL 15 IS 3 BP 536 EP 542 DI 10.1158/1055-9965.EPI-05-0749 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 024AV UT WOS:000236168200023 PM 16537713 ER PT J AU Rollison, DE Engels, EA Halsey, NA Shah, KV Viscidi, RP Helzlsouer, KJ AF Rollison, DE Engels, EA Halsey, NA Shah, KV Viscidi, RP Helzlsouer, KJ TI Prediagnostic circulating antibodies to JC and BK human polyomaviruses and risk of non-Hodgkin lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN NEUROTROPIC POLYOMAVIRUS; SIMIAN-VIRUS-40 DNA; CHROMOSOMAL DAMAGE; HUMAN-LYMPHOCYTES; VIRUS; INFECTION; ASSOCIATION; INDIVIDUALS; HERPESVIRUS; PARTICLES AB Viral infections have been associated with increased risk of non-Hodgkin's lymphoma WHO. We conducted a nested case-control study to investigate the association between prediagnostic serum antibodies to the human polyomaviruses, JC (JCV) and BK (BKV), and subsequent risk of NHL. Two research serum banks were established in Washington County, Maryland, in 1974 and 1989, with the collection of blood samples from > 45,000 volunteers. Incident NHL cases diagnosed through 2002 (n = 170) were identified among participants by linkage to population-based cancer registries. Two controls were matched to each case (it = 340) on age, sex, and blood draw date. Prediagnostic IgG antibodies to JCV and BKV were measured using virus-like particle ELISA. Associations between JCV and BKV antibody seropositivity and NHL were estimated using conditional logistic regression. Overall, neither antibodies to JCV [odds ratio (OR), 0.83; 95% confidence interval (95% CI), 0.56-1.23] nor BKV (OR, 0.98; 95% CI, 0.64-1.48) were associated with an increased risk of NHL. Results were similar after stratification by NHL subtype or induction period and adjustment for EBV seropositivity. Among those who donated blood in both 1974 and 1989, an increase in JCV antibody levels over time was associated with a 4-fold increased risk of NHL compared with a steep decline in antibody levels (OR, 4.59; 95% Cl, 1.30-16.25; P-trend = 0.02). Whereas JCV seropositivity was not associated with NHL overall, the finding of an increased risk of NHL associated with increasing antibody levels among those who were seropositive at baseline warrants further research into factors influencing reactivation of JCV infection. C1 H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL 33612 USA. Johns Hopkins Sch Med, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Int Hlth, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. St Johns Mercy Med Ctr, Ctr Prevent & Res, Baltimore, MD USA. NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Rollison, DE (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Div Canc Prevent & Control, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM rollisde@moffit.usf.edu FU Intramural NIH HHS; NCI NIH HHS [2 T32 CA09314-19, 5 U01 CA086308]; NIA NIH HHS [AG18033] NR 34 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2006 VL 15 IS 3 BP 543 EP 550 DI 10.1158/1055-9965.EPI-05-0728 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 024AV UT WOS:000236168200024 PM 16537714 ER PT J AU Savage, SA Hou, LF Lissowska, J Chow, WH Zatonski, W Chanock, SJ Yeager, M AF Savage, SA Hou, LF Lissowska, J Chow, WH Zatonski, W Chanock, SJ Yeager, M TI Interleukin-8 polymorphisms are not associated with gastric cancer risk in a Polish population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID HELICOBACTER-PYLORI; GENE; INFLAMMATION; CARCINOMA; EPIDEMIOLOGY; PATHOGENESIS; PROGRESSION; PREVALENCE; SURVIVAL; ARTICLE C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. M Sklodowska Curie Inst Oncol, Ctr Canc, Warsaw, Poland. NCI, Sci Applicat Int Corp Frederick Inc, Core Genotyping Facil, Gaithersburg, MD USA. RP Savage, SA (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8718 Grovemont Circle, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 30 TC 43 Z9 47 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2006 VL 15 IS 3 BP 589 EP 591 DI 10.1158/1055-9965.EPI-05-0887 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 024AV UT WOS:000236168200032 PM 16537722 ER PT J AU Narazaki, M Tosato, G AF Narazaki, M Tosato, G TI Canstatin: An inhibitor of angiogenesis and tumor growth revisited SO CANCER JOURNAL LA English DT Editorial Material ID ENDOTHELIAL-CELLS; ALPHA(V)BETA(3); THROMBOSPONDIN; EXPRESSION; CARCINOMA; FRAGMENT; LUNG; VEGF C1 Natl Canc Inst, Canc Res Ctr, Basic Res Labs, Bethesda, MD USA. RP Tosato, G (reprint author), Bldg 10,12C205,10 Ctr Dr, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov OI narazaki, masashi/0000-0002-5613-4409 NR 21 TC 5 Z9 11 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2006 VL 12 IS 2 BP 110 EP 112 PG 3 WC Oncology SC Oncology GA 036JR UT WOS:000237067900006 PM 16630401 ER PT J AU Aziz, NM AF Aziz, Noreen M. TI State of the science on nursing approaches - Managing late and long term sequelae of cancer and cancer treatment - Foreword SO CANCER NURSING LA English DT Editorial Material ID SURVIVORSHIP RESEARCH; OPPORTUNITY; CHALLENGE C1 NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. RP Aziz, NM (reprint author), NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2006 VL 29 IS 2 SU S BP 3 EP 3 DI 10.1097/00002820-200603002-00001 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 097AY UT WOS:000241419800001 ER PT J AU Mellon, S Northouse, LL Weiss, LK AF Mellon, Suzanne Northouse, Laurel L. Weiss, Linda K. TI A population-based study of the quality of life of cancer survivors and their family caregivers SO CANCER NURSING LA English DT Article DE cancer; family caregiver; quality of life; survivorship ID RECURRENT BREAST-CANCER; POSTTRAUMATIC STRESS SYMPTOMS; COUPLES ADJUSTMENT; LONG-TERM; PSYCHOLOGICAL DISTRESS; LONGITUDINAL ANALYSIS; GENDER-DIFFERENCES; COPING STRATEGIES; SOCIAL SUPPORT; FOLLOW-UP AB Although survival rates for all cancers continue to increase, few studies have examined the quality of life of both cancer survivors and family caregivers during the survivorship period after treatment has ended. Information is lacking on the stressors, resources, meaning, and quality of life reported by survivors and family caregivers and the interrelationship between survivors' and family caregivers, quality of life. A stratified, random sample of 123 cancer survivors and 123 family caregivers (N = 246) were interviewed in an exploratory, cross-sectional design 1-6 years after cancer treatment had ended. Approximately half (N = 62) of the dyads were white and half (N = 61) were African American. Results indicated that cancer survivors reported significantly higher quality of life, less fear of cancer recurrence, and more support than their family caregivers. The strongest predictors for cancer survivors' quality of life were family stressors, social support, meaning of the illness, and employment status, whereas the strongest predictors for family caregivers' quality of life were fear of recurrence and social support. Both the survivor's and family caregiver's quality of life independently contributed to the other's quality of life. Findings from this study suggest the importance of including both survivors and family caregivers in programs of care. C1 Univ Detroit Mercy, Coll Hlth Profess, Detroit, MI 48221 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Natl Canc Inst, Bethesda, MD USA. RP Mellon, S (reprint author), Univ Detroit Mercy, Coll Hlth Profess, 4001 W McNicholas, Detroit, MI 48221 USA. EM mellonsk@udmercy.edu FU NCI NIH HHS [N01-CN-65064] NR 82 TC 102 Z9 104 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD MAR-APR PY 2006 VL 29 IS 2 BP 120 EP 131 DI 10.1097/00002820-200603000-00007 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA 095HF UT WOS:000241298100006 PM 16565621 ER PT J AU Bloomston, M Zhou, JX Rosemurgy, AS Frankel, W Muro-Cacho, CA Yeatman, TJ AF Bloomston, M Zhou, JX Rosemurgy, AS Frankel, W Muro-Cacho, CA Yeatman, TJ TI Fibrinogen gamma overexpression in pancreatic cancer identified by large-scale proteomic analysis of serum samples SO CANCER RESEARCH LA English DT Article ID MASS-SPECTROMETRY; PROTEIN; CA19-9; CELLS; GELS AB Detection of serum markers for pancreatic cancer has been elusive. Although CA 19-9 is most commonly used, its sensitivity and specificity are modest. We used large-scale proteomics to identify potential serum markers for pancreatic cancer. Samples were analyzed using high-resolution two-dimensional gel electrophoresis to identify differentially expressed proteins in 32 normal and 30 pancreatic cancer patients. Up to 1,744 protein spots were resolved for each serum sample. Candidate proteins were identified using mass spectrometry. ANOVA was used to identify proteins that could discriminate cancer from normal sera. Serum fibrinogen level was also measured using enzymatic assay. Immunohistochemistry was used to detect fibrinogen in resected pancreatic cancers. One hundred fifty-four proteins were commonly overexpressed in all pancreatic cancers. Nine protein spots (four with identifications by mass spectrometry) could effectively separate cancer from normal controls using cross-validation. These proteins successfully discriminated all pancreatic cancer samples (30 of 30) and 94% of normal (30 of 32) samples. Prominent among these candidates was fibrinogen gamma, which was subsequently confirmed to be overexpressed in pancreatic cancer sera by enzymatic analysis (54.1 +/- 64.1 versus 0.0 +/- 0.0 mg/dL, P < 0.05) and tissue by immunohistochemistry (67% versus 29%, P < 0.05) relative to normal pancreas. Proteomic analysis combining two-dimensional gel electrophoresis and mass spectrometry successfully identified 154 potential serum markers for pancreatic cancer. Of these, fibrinogen gamma, a protein associated with the hypercoagulable state of pancreatic cancer, discriminated cancer from normal sera. Fibrinogen is a potential tumor marker in pancreatic cancer. C1 H Lee Moffitt Canc Ctr & Res Inst, Div Interdisciplinary Oncol, Tampa, FL 33612 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. NIAID, Immunopathol Lab, NIH, Rockville, MD USA. Univ S Florida, Dept Surg, Tampa, FL 33620 USA. RP Zhou, JX (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Div Interdisciplinary Oncol, 12902 Magnolia Dr,SRB-2, Tampa, FL 33612 USA. EM yeatman@moffitt.usf.edu RI Bloomston, Mark/E-2767-2011 FU NCI NIH HHS [R01 CA112215-03] NR 22 TC 60 Z9 66 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2006 VL 66 IS 5 BP 2592 EP 2599 DI 10.1158/0008-5472.CAN-05-3659 PG 8 WC Oncology SC Oncology GA 019HO UT WOS:000235826400016 PM 16510577 ER PT J AU Gustchina, A Jaskolski, M Wlodawer, A AF Gustchina, A Jaskolski, M Wlodawer, A TI Lessons learned fighting HIV can be applied to anti-cancer drug design SO CELL CYCLE LA English DT Article DE HTLV-1; HIV-1; Aids; cancer; leukemia; drug design; protease ID T-CELL LEUKEMIA C1 NCI, Prot Struct Sect, Lab Macromol Crystallog, Frederick, MD 21702 USA. Adam Mickiewicz Univ Poznan, Dept Crystallog, Poznan, Poland. Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Lab Macromol Crystallog, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov NR 8 TC 6 Z9 6 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 1 PY 2006 VL 5 IS 5 BP 463 EP 464 DI 10.4161/cc.5.5.2490 PG 2 WC Cell Biology SC Cell Biology GA 041QT UT WOS:000237471500001 PM 16479175 ER PT J AU Tong, WH Rouault, TA AF Tong, WH Rouault, TA TI Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis SO CELL METABOLISM LA English DT Article ID RESPONSIVE ELEMENT-BINDING; SACCHAROMYCES-CEREVISIAE; SCAFFOLD PROTEIN; SUPEROXIDE-DISMUTASE; REGULATORY PROTEIN; OXIDATIVE STRESS; ARABIDOPSIS-THALIANA; FRIEDREICH ATAXIA; HYDROGEN-PEROXIDE; 4FE-4S CLUSTER AB Iron-sulfur(Fe-S) clusters are required for the functions of mitochondrialaconitase, mammalian iron regulatory protein 1, and many other proteins in multiple subcellular compartments. Recent studies in Saccharomyces cerevisiae indicated that Fe-S cluster biogenesis also has an important role in mitochondrial iron homeostasis. Here we report the functional analysis of the mitochondrial and cytosolic isoforms of the human Fe-S cluster scaffold protein, ISCU. Suppression of human ISCU by RNAi not only inactivated mitochondrial and cytosolic aconitases in a compartment-specific manner but also inappropriately activated the iron regulatory proteins and disrupted intracellular iron homeostasis. Furthermore, endogenous ISCU levels were suppressed by iron deprivation. These results provide evidence for a coordinated response to iron deficiency that includes activation of iron uptake, redistribution of intracellular iron, and decreased utilization of iron in Fe-S proteins. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM trou@helix.nih.gov FU Intramural NIH HHS NR 63 TC 147 Z9 152 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR PY 2006 VL 3 IS 3 BP 199 EP 210 DI 10.1016/j.cmet.2006.02.003 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 019YS UT WOS:000235875300008 PM 16517407 ER PT J AU Howe, D Heinzen, RA AF Howe, D Heinzen, RA TI Coxiella burnetii inhabits a cholesterol-rich vacuole and influences cellular cholesterol metabolism SO CELLULAR MICROBIOLOGY LA English DT Article ID HAMSTER OVARY CELLS; LOW-DENSITY-LIPOPROTEIN; NIEMANN-PICK-DISEASE; CHLAMYDIA-TRACHOMATIS; LIPID RAFTS; LEISHMANIA-AMAZONENSIS; ENDOPLASMIC-RETICULUM; PERSISTENT INFECTION; AUTOPHAGIC VACUOLES; Q-FEVER AB Coxiella burnetii directs the synthesis of a large parasitophorous vacuole (PV) required for replication. While some lysosomal characteristics of the PV have been described, the origin and composition of the PV membrane is largely undefined. Cholesterol is an essential component of mammalian cell membranes where it plays important regulatory and structural roles. Here we investigated the role of host cholesterol in biogenesis and maintenance of the C. burnetii PV in Vero cells. The C. burnetii PV membrane stained with filipin and was positive for the lipid raft protein flotillin-1, suggesting PV membranes are enriched in cholesterol and contain lipid raft microdomains. C. burnetii infection increased host cell cholesterol content by 1.75-fold with a coincident upregulation of host genes involved in cholesterol metabolism. Treatment with U18666A, lovastatin, or 25-hydroxycholesterol, pharmacological agents that inhibit cholesterol uptake and/or biosynthesis, altered PV morphology and partially inhibited C. burnetii replication. Complete inhibition of C. burnetii PV development and replication was observed when infected cells were treated with imipramine or ketoconazole, inhibitors of cholesterol uptake and biosynthesis respectively. We conclude that C. burnetii infection perturbs host cell cholesterol metabolism and that free access to host cholesterol stores is required for optimal C. burnetii replication. C1 NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 60 TC 64 Z9 65 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD MAR PY 2006 VL 8 IS 3 BP 496 EP 507 DI 10.1111/j.1462-5822.2005.00641.x PG 12 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 010UC UT WOS:000235222400011 PM 16469060 ER PT J AU Zmuda-Trzebiatowska, E Oknianska, A Manganiello, V Degerman, E AF Zmuda-Trzebiatowska, E Oknianska, A Manganiello, V Degerman, E TI Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis in primary rat adipocytes SO CELLULAR SIGNALLING LA English DT Article DE PDE3B; PDE4; Epac; GLUT-4; glucose uptake; lipogenesis; adipocyte ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; MEDIATED SIGNAL-TRANSDUCTION; DEPENDENT PROTEIN-KINASE; PANCREATIC BETA-CELL; ADIPOSE-CELLS; FAT-CELLS; GLUT4-CONTAINING VESICLES; CAMP-PHOSPHODIESTERASE; ANTILIPOLYTIC ACTION; TRANSPORTER GLUT4 AB In adipocytes, phosphorylation and activation of PDE3B is a key event in the antilipolytic action of insulin. The role of PDE4, another PDE present in adipocytes, is not yet known. In this work we investigate the role of PDE3B and PDE4 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis. Inhibition of PDE3 (OPC3911, milrinone) but not PDE4 (RO 20-1724) lowered insulin-induced glucose uptake and lipogenesis, especially in the presence of isoproterenol (a general beta-adrenergic agonist), CL316243, a selective beta 3-adrenergic agonist, and pituitary adenylate cyclase-activating peptide. The inhibitory effect of OPC3911 was associated with reduced translocation of GLUT-4 from the cytosol to the plasma membrane. Both OPC3911 and RO 20-1724 increased protein kinase A (PKA) activity and lipolysis. H89, a PKA inhibitor, did not affect OPC3911-mediated inhibition of insulin-induced glucose uptake and lipogenesis, whereas 8-pCPT-2'-O-Me-cAMP, an Epac agonist which mediates PKA independent cAMP signaling events, mimicked all the effects of OPC3911. Insulin-mediated activation of protein kinase B, a kinase involved in insulin-induced glucose uptake, was apparently not altered by OPC3911. In summary, our data suggest that PDE3B, but not PDE4, contributes to the regulation of insulin-induced glucose uptake, GLUT-4 translocation, and lipogenesis presumably by regulation of a cAMP/Epac signalling mechanisms. (c) 2005 Elsevier Inc. All rights reserved. C1 Biomed Ctr, Dept Expt Med Sci, S-22184 Lund, Sweden. NHLB, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Zmuda-Trzebiatowska, E (reprint author), Biomed Ctr, Dept Expt Med Sci, C11, S-22184 Lund, Sweden. EM emilia.zmuda-trzebiatowska@medkem.lu.se NR 51 TC 45 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAR PY 2006 VL 18 IS 3 BP 382 EP 390 DI 10.1016/j.cellsig.2005.05.007 PG 9 WC Cell Biology SC Cell Biology GA 993LE UT WOS:000233954800012 PM 15961276 ER PT J AU Radley, JJ Rocher, AB Miller, M Janssen, WGM Liston, C Hof, PR McEwen, BS Morrison, JH AF Radley, JJ Rocher, AB Miller, M Janssen, WGM Liston, C Hof, PR McEwen, BS Morrison, JH TI Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex SO CEREBRAL CORTEX LA English DT Article DE axospinous synapse; cell loading; dendritic spine; post-traumatic stress disorder; prefrontal; stress ID HIPPOCAMPAL PYRAMIDAL NEURONS; ANTERIOR CINGULATE CORTEX; APICAL DENDRITES; AMYGDALA; DISORDER; MORPHOLOGY; SYNAPSES; ATROPHY; DENSITY; CA3 AB The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and in the regulation of stress-induced hypothalamic-pituitary-adrenal (HPA) activity. Here we examined the effect of repeated restraint stress on dendritic spine number in the medial PFC. Rats were perfused after receiving 21 days of daily restraint stress, and intracellular iontophoretic injections of Lucifer Yellow were carried out in layer II/III pyramidal neurons in the anterior cingulate and prelimbic cortices. We found that stress results in a significant (16%) decrease in apical dendritic spine density in medial PFC pyramidal neurons, and confirmed a previous observation that total apical dendritic length is reduced by 20% in the same neurons. We estimate that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress. A decrease in medial PFC dendritic spines may not only be indicative of a decrease in the total population of axospinous synapses, but may impair these neurons' capacity for biochemical compartmentalization and plasticity in which dendritic spines play a major role. Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired. C1 Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. NIMH, Ctr Fear & Anxiety, New York, NY 10003 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. RP Radley, JJ (reprint author), Salk Inst Biol Studies, Neuronal Struct & Funct Lab, POB 85800, San Diego, CA 92310 USA. EM radley@salk.edu; john.morrison@mssm.edu RI Morrison, John/F-9229-2012 FU NIMH NIH HHS [MH 58911] NR 54 TC 327 Z9 342 U1 3 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2006 VL 16 IS 3 BP 313 EP 320 DI 10.1093/cercor/bhi104 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 011OI UT WOS:000235277500002 PM 15901656 ER PT J AU Pessoa, L Japee, S Sturman, D Ungerleider, LG AF Pessoa, L Japee, S Sturman, D Ungerleider, LG TI Target visibility and visual awareness modulate amygdala responses to fearful faces SO CEREBRAL CORTEX LA English DT Article DE amygdala; awareness; emotion; fear; fMRI ID EVENT-RELATED FMRI; EMOTIONAL FACIAL EXPRESSIONS; SEROTONIN TRANSPORTER; UNCONSCIOUS PERCEPTION; GENETIC-VARIATION; FUNCTIONAL MRI; HUMAN BRAIN; STIMULI; ATTENTION; RECOGNITION AB The goals of the present study were twofold. First, we wished to investigate the neural correlates of aware and unaware emotional face perception after characterizing each subject's behavioral performance via signal detection theory methods. Second, we wished to investigate the extent to which amygdala responses to fearful faces depend on the physical characteristics of the stimulus independently of the percept. We show that amygdala responses depend on visual awareness. Under conditions in which subjects were not aware of fearful faces flashed for 33 ms, no differential activation was observed in the amygdala. On the other hand, differential activation was observed for 67 ms fearful targets that the subjects could reliably detect. When trials were divided into hits, misses, correct rejects, and false alarms, we show that target visibility is an important factor in determining amygdala responses to fearful faces. Taken together, our results further challenge the view that amygdala responses occur automatically. C1 Brown Univ, Dept Psychol, Providence, RI 02912 USA. NIMH, Lab Brain & Cognit, Bethesda, MD USA. RP Pessoa, L (reprint author), Brown Univ, Dept Psychol, 89 Waterman St, Providence, RI 02912 USA. EM pessoa@brown.edu RI Sturman, David/K-6004-2012 FU NIMH NIH HHS [1R01 MH 071589-01] NR 59 TC 149 Z9 154 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2006 VL 16 IS 3 BP 366 EP 375 DI 10.1093/cercorbhi115 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 011OI UT WOS:000235277500008 PM 15930371 ER PT J AU Lazarus, LH Bryant, SD Salvadori, S Geurrini, R Balboni, G Tsuda, Y Okada, Y AF Lazarus, LH Bryant, SD Salvadori, S Geurrini, R Balboni, G Tsuda, Y Okada, Y TI Dimethyltyrosine, the viagra of opioids SO CHEMICAL RESEARCH IN CHINESE UNIVERSITIES LA English DT Article; Proceedings Paper CT 5th Symposium on Frontiers in Protein Chemistry and Biotechnology/9th China-Korea Regional Symposium on Biochemistry CY 2005 CL Changchun, PEOPLES R CHINA SP Natl Nat Sci Fdn, Minist Educ Sci & Engn Fdn DE dimethyltryrosine; opioid; agonist ID DMT-TIC PHARMACOPHORE; RECEPTOR SELECTIVITY; BIOLOGICAL EVALUATION; PEPTIDE ANTAGONISTS; DELTA; ANALOGS; MU; BINDING; DESIGN; POTENT C1 NIEHS, LCBRA, Peptide Neurochem, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Cagliari, Dept Toxicol, I-109126 Cagliari, Italy. Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 6512180, Japan. RP Lazarus, LH (reprint author), NIEHS, LCBRA, Peptide Neurochem, POB 12233, Res Triangle Pk, NC 27709 USA. EM lazarus@niehs.nih.gov NR 46 TC 1 Z9 1 U1 0 U2 0 PU HIGHER EDUCATION PRESS PI BEIJING PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA SN 1005-9040 EI 2210-3171 J9 CHEM RES CHINESE U JI Chem. Res. Chin. Univ. PD MAR PY 2006 VL 22 IS 2 BP 258 EP 262 DI 10.1016/S1005-9040(06)60092-5 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 029KJ UT WOS:000236560900034 ER PT J AU Cysyk, RL Parker, RJ Barchi, JJ Steeg, PS Hartman, NR Strong, JA AF Cysyk, RL Parker, RJ Barchi, JJ Steeg, PS Hartman, NR Strong, JA TI Reaction of geldanamycin and C17-substituted analogues with glutathione: Product identifications and pharmacological implications SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HEAT-SHOCK-PROTEIN; HERBIMYCIN-A; FISCHER-344 RATS; ANTITUMOR AGENT; KINASE-ACTIVITY; V-SRC; METABOLISM; INHIBITION; HSP90; DERIVATIVES AB 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and 17-allylamino-17-demethoxy-geldanamycin (17-AAG) are two derivatives of geldanamycin (GA) that are currently undergoing clinical evaluation as anticancer agents. These agents bind to heat shock protein 90 (hsp90), resulting in the destabilization of client proteins and inhibition of tumor growth. In a search for the mechanism of hepatotoxicity, which is a dose-limiting toxicity for these agents, we found that GA and its derivatives, 17-AAG and 17-DMAG, react chemically (i.e., nonenzymatically) with glutathione (GSH). A combination of liquid chromatography/electrospray ionization/mass spectrometry and nuclear magnetic resonance analyses were used to identify the product of this reaction as a GSH adduct in which the thiol group of GSH is substituted in the 19-position of the benzoquinone ring. The reaction proceeds rapidly with GA and 17-DMAG (half-lives of approximately 1.5 and 36 min, respectively) and less rapidly with 17-AAG and its major metabolite, 17-AG (half-lives of approximately 9.8 and 16.7 h). The reaction occurs at pH 7.0, 37 degrees C, and a physiological concentration of GSH, indicating that cellular GSH could play a role in modulating the cellular toxicity of these agents and therefore be a factor in their mechanism of differential toxicity. Moreover, reactions with thiol groups of critical cellular proteins could be important to the mechanism of toxicity with this class of anticancer agents. C1 US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. NCI, Mol Therapeut Program, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. RP Strong, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, White Oak Bldg 64,Room 2026,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM strongj@cder.fda.gov RI Barchi Jr., Joseph/N-3784-2014 NR 28 TC 71 Z9 73 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2006 VL 19 IS 3 BP 376 EP 381 DI 10.1021/tx050237e PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 028BE UT WOS:000236459700005 PM 16544941 ER PT J AU Sternberg, KJ Lamb, ME Guterman, E Abbott, CB AF Sternberg, KJ Lamb, ME Guterman, E Abbott, CB TI Effects of early and later family violence on children's behavior problems and depression: A longitudinal, multi-informant perspective SO CHILD ABUSE & NEGLECT LA English DT Article DE family violence; child abuse; internalizing behavior problems; externalizing behavior problems; maladjustment ID DOMESTIC VIOLENCE; PSYCHOMETRIC PROPERTIES; REFERRED CHILDREN; EARLY-CHILDHOOD; PHYSICAL ABUSE; WITNESSES; PSYCHOPATHOLOGY; METAANALYSIS; AGGRESSION; ATTACHMENT AB Objectives: To examine the effects of different forms of family violence at two developmental stages by assessing a sample of 110 Israeli children, drawn from the case files of Israeli family service agencies, studied longitudinally in both middle childhood and adolescence. Methods: Information about the children's adjustment was obtained from parents, teachers, and the children themselves when the children averaged 10.6 and 15.9 years of age using the Child Behavior Checklist (CBCL), Teacher Report Form (TRF), Youth Self-Report (YSR), and Children's Depression Inventory (CDI). Information about the history of family violence was obtained from the mothers, fathers, children, and social workers. Results: The results paint a mixed picture of the effects of family violence on children and adolescents. The relationship between concurrent behavior problems and abuse group varied by informant and study phase, although they were strongest when children were the informants. Predictions regarding the relationship between early abuse and later adjustment were only partially confirmed. Different informants did not agree about which groups of children were most adversely affected, there was little stability over time in the pattern of reported effects, and children were more likely than other informants to report levels of maladjustment that varied depending on recent or concurrent exposure to family violence. Many families changed their abuse status over time, and children who were new victims at follow-up had the most internalizing problems. Girls were found to be at more risk for internalizing and externalizing behavior problems than boys. Conclusions: Multiple informants are necessary to evaluate and assess the effects of family violence on children's behavior. Younger children may be more susceptible to the effects of family violence than older children, but problems manifest by some children may not carry over to adolescence. Changes in family and parenting practices, as well as in children's capacity to appraise and cope with family violence may help mitigate the adverse effects of family violence. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Cambridge, Fac Social & Polit Sci, Dept Social & Dev Psychol, Cambridge CB2 3RQ, England. NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Lamb, ME (reprint author), Univ Cambridge, Fac Social & Polit Sci, Dept Social & Dev Psychol, Free Sch Lane, Cambridge CB2 3RQ, England. NR 59 TC 68 Z9 74 U1 3 U2 35 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD MAR PY 2006 VL 30 IS 3 BP 283 EP 306 DI 10.1016/j.chiabu.2005.10.008 PG 24 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 028AB UT WOS:000236456600006 PM 16524627 ER PT J AU Guan, M Zhou, XL Soulitzis, N Spandidos, DA Popescu, NC AF Guan, M Zhou, XL Soulitzis, N Spandidos, DA Popescu, NC TI Aberrant methylation and deacetylation of deleted in liver cancer-1 gene in prostate cancer: Potential clinical applications SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; HUMAN BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; DLC-1 GENE; PROMOTER HYPERMETHYLATION; LUNG-CARCINOMA; FRAGILE SITES; CELL-GROWTH; RHO GTPASES; EXPRESSION AB Purpose: The deleted in liver cancer-1 (DLC-1) gene that encodes a Rho GTPase-activating protein with tumor suppressor function is located on chromosome 8p21-22, a region frequently deleted in prostate carcinomas. This study was designed to determine whether DLC-1 is deregulated in prostate carcinomas and to assess the contribution of DLC-1 alterations to prostate carcinogenesis. Experimental Design: Primary prostate carcinomas, prostate carcinoma cell lines, benign prostatic hyperplasias, and normal prostatic tissues were examined for detection of functional and structural alterations of the DLC-1 gene by real-time PCR, methylation-specific PCR, and Southern and Western blots. Results: Down-regulation or loss of DCL-1 mRNA expression was detected in 10 of 27 (37%) prostate carcinomas, 3 of 5 (60%) prostate carcinoma cell lines, and 5 of 21 (24%) benign prostatic hyperplasias. DLC-1 promoter methylation was identified in 13 of 27 (48%) prostate carcinomas and 2 matching normal tissues and in 15 of 21 (71%) benign prostatic hyperplasias but was absent in 10 normal prostatic tissues from noncancerous individuals. Genomic deletions were found in only 3 prostate carcinomas and 1 benign prostatic hyperplasia. DLC-1 protein was not detected in 8 of 27 (30%) prostate carcinomas and 11 of 21 (52%) benign prostatic hyperplasias. Methylation of DLC-1 correlated with age in prostate carcinoma patients (P = 0.006) and with prostate-specific antigen blood levels in benign prostatic hyperplasia patients (P = 0.029). Treatment of the three prostate carcinoma cell lines (PC-3, LNCaP, and 22 Rv1) expressing a low level of DLC-1 transcripts with inhibitors of DNA methyltransferase or histone deacetylase increased DLC-1 expression. Conclusions: These results show that the transcriptional silencing of DLC-1 by two epigenetic mechanisms is common and may be involved in the pathogenesis of prostate carcinomas and benign prostatic hyperplasias and could have potential clinical application in the early detection and gene therapy of prostate cancer. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Crete, Sch Med, Lab Clin Virol, Iraklion, Crete, Greece. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Room 4128B,37 Convent Dr,MSC 4262,Bldg 37, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov FU Intramural NIH HHS NR 47 TC 69 Z9 80 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2006 VL 12 IS 5 BP 1412 EP 1419 DI 10.1158/1078-0432.CCR-05-1906 PG 8 WC Oncology SC Oncology GA 021MT UT WOS:000235988000004 PM 16533763 ER PT J AU Robey, RW Zhan, ZR Piekarz, RL Kayastha, GL Fojo, T Bates, SE AF Robey, RW Zhan, ZR Piekarz, RL Kayastha, GL Fojo, T Bates, SE TI Increased MDR1 expression in normal and malignant peripheral blood mononuclear cells obtained from patients receiving depsipeptide (FR901228, FK228, NSC630176) SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; BREAST-CANCER CELLS; SUBEROYLANILIDE HYDROXAMIC ACID; CHRONIC LYMPHOCYTIC-LEUKEMIA; P-GLYCOPROTEIN EXPRESSION; THYROID-CARCINOMA CELLS; ADVANCED SOLID TUMORS; PHASE-I TRIAL; MULTIDRUG-RESISTANCE; SODIUM-BUTYRATE AB The increased expression of markers associated with a differentiated phenotype, such as P-glycoprotein (Pgp), follows treatment with histone deacetylase inhibitors. Because depsipeptide (FR901228, FK228, NSC630176) is a substrate for Pgp, up-regulation of the gene that encodes it, MDR1, would mean that depsipeptide induces its own mechanism of resistance. To examine the effect of depsipeptide on expression of ATP-binding cassette transporters associated with multidrug resistance, the kidney cancer cell lines 108, 121, 127, and 143 were treated with depsipeptide and evaluated by quantitative reverse transcription-PCR. Increased levels of MDR1 (1.3- to 6.3-fold) and ABCG2 (3.2- to 11.1-fold) but not MRP1 (0.9- to 1.3-fold) were observed. The induced Pgp transported the fluorescent substrates rhodamine 123, bisantrene, calcein-AM, BODIPY-vinblastine, and BODIPY-paclitaxel. In normal peripheral blood mononuclear cells (PBMC) and circulating tumor cells obtained from patients receiving depsipeptide, increased levels of histone H3 acetylation were found. We next examined MDR1 levels in normal and malignant PBMCs obtained from 15 patients enrolled in clinical trials with depsipeptide and detected up to a 6-fold increase in normal PBMCs and up to an 8-fold increase in circulating tumor cells after depsipeptide administration. In one patient with Sezary syndrome, increased MDR1 gene expression was accompanied by increased cell surface Pgp expression in circulating Sezary cells as determined by measurement of MRK-16 staining by flow cytometry. These studies suggest that depsipeptide induces its own mechanism of resistance and thus provide a basis for clinical trials evaluating depsipeptide in combination with a Pgp inhibitor. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Robey, RW (reprint author), 9000 Rockville Pike,Bldg 10,Room 12C103, Bethesda, MD 20892 USA. EM robeyr@mail.nih.gov FU Intramural NIH HHS NR 50 TC 68 Z9 70 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2006 VL 12 IS 5 BP 1547 EP 1555 DI 10.1158/1078-0432.CCR-05-1423 PG 9 WC Oncology SC Oncology GA 021MT UT WOS:000235988000021 PM 16533780 ER PT J AU Sviridov, D Meilinger, B Drake, SK Hoehn, GT Hortin, GL AF Sviridov, D Meilinger, B Drake, SK Hoehn, GT Hortin, GL TI Coelution of other proteins with albumin during size-exclusion HPLC: Implications for analysis of urinary albumin SO CLINICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIABETES-MELLITUS; DIAGNOSTIC-SIGNIFICANCE; IMMUNOGLOBULIN-G; PLASMA-PROTEINS; EXCRETION; MICROALBUMINURIA; ALPHA(1)-MICROGLOBULIN; GLYCOPROTEIN; ALPHA-1-MICROGLOBULIN AB Background: Size-exclusion HPLC has been used as an alternative to immunoassays for quantifying urinary albumin (microalbumin). Systematically higher values for the HPLC method have been proposed to result from nonimmunoreactive albumin. Methods: We evaluated separation of purified proteins and urinary components by size-exclusion HPLC using a Zorbax Bio Series GF-250 column eluted with phosphate-buffered saline. Urinary components eluting in the "albumin" peak were analyzed by mass spectrometry and reversed-phase HPLC. Results: Several proteins, such as transferrin, alpha(1)-proteinase inhibitor, alpha(1)-acid glycoprotein, and alpha(2)-HS glycoprotein, analyzed as purified components, were not resolved from albumin by size-exclusion HPLC. Peaks for other proteins, such as IgG and urinary components identified as dimers of alpha(1)-microglobulin and immunoglobulin light chains, overlapped with the albumin peak. Profiles of urine specimens showed variable amounts of components overlapping with albumin. Furthermore, the albumin peak obtained by size-exclusion HPLC was found by mass spectrometry and reversed-phase HPLC to contain multiple components in addition to albumin. Conclusions: Size-exclusion HPLC does not resolve albumin from several other proteins in urine. The albumin peak resolved by this technique, although predominantly composed of albumin, contains several coeluting globulins that would contribute to overestimation of albumin concentration by size-exclusion HPLC. (C) 2006 American Association for Clinical Chemistry. C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov FU Intramural NIH HHS NR 43 TC 54 Z9 60 U1 1 U2 13 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2006 VL 52 IS 3 BP 389 EP 397 DI 10.1373/clinchem.2005.057323 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 017DS UT WOS:000235674900007 PM 16397014 ER PT J AU O'Brien, K Hussain, N Warady, BA Kleiner, DE Kleta, R Bernardini, I Heller, T Gahl, WA AF O'Brien, K Hussain, N Warady, BA Kleiner, DE Kleta, R Bernardini, I Heller, T Gahl, WA TI Nodular regenerative hyperplasia and severe portal hypertension in cystinosis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID TERM CYSTEAMINE THERAPY; OF-THE-LITERATURE; NEPHROPATHIC CYSTINOSIS; SWALLOWING DYSFUNCTION; RENAL-TRANSPLANTATION; CORNEAL CRYSTALS; CTNS MUTATIONS; LIVER; DISEASE; GENE AB Background & Aims: Cystinosis is a rare autosomal-recessive disorder characterized by the intralysosomal accumulation of cystine, which is responsible for widespread tissue destruction. Liver biopsy specimens of patients with cystinosis show cystine crystal formation in Kupffer cells. However, significant liver disease and portal hypertension is not a common complication of cystinosis. We report the case histories of 2 young men with poorly treated nephropathic cystinosis who developed noncirrhotic portal hypertension with evidence of nodular regenerative hyperplasia (NRH). Methods: Liver biopsy examinations, upper and lower endoscopy with biopsy examination, imaging studies, venous pressure measurements, and laboratory investigations were used to evaluate the causes of the liver disease and portal hypertension. Results: Histologic examination of liver biopsy specimens from both patients showed changes characteristic of NRH with portal hypertension documented by measurement of pressure gradients. In addition, endoscopy in the first patient showed varices and portal hypertensive gastropathy. Conclusions: NRH was confirmed by histologic examination of the liver in both patients and is the likely cause of their portal hypertension. NRH may represent a rare, late complication of cystinosis, although the mechanism remains undefined. C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Childrens Mercy Hosp, Nephrol Sect, Kansas City, MO 64108 USA. RP Gahl, WA (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 49 TC 16 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2006 VL 4 IS 3 BP 387 EP 394 DI 10.1053/S1542-3565(05)01184-5 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 023AF UT WOS:000236096700022 PM 16527704 ER PT J AU Marroni, F Pastrello, C Benatti, P Torrini, M Barana, D Cordisco, EL Viel, A Mareni, C Oliani, C Genuardi, M Bailey-Wilson, JE de Leon, MP Presciuttini, S AF Marroni, F Pastrello, C Benatti, P Torrini, M Barana, D Cordisco, EL Viel, A Mareni, C Oliani, C Genuardi, M Bailey-Wilson, JE de Leon, MP Presciuttini, S TI A genetic model for determining MSH2 and MLH1 carrier probabilities based on family history and tumor microsatellite instability SO CLINICAL GENETICS LA English DT Article DE carrier probability; HNPCC; MSI; mutation-predicting models ID NONPOLYPOSIS COLORECTAL-CANCER; LYNCH-SYNDROME-I; SELECTION-STRATEGIES; MUTATIONS; RISK; BRCA1; SUSCEPTIBILITY; GUIDELINES; HMLH1; HMSH2 AB Mutation-predicting models can be useful when deciding on the genetic testing of individuals at risk and in determining the cost effectiveness of screening strategies at the population level. The aim of this study was to evaluate the performance of a newly developed genetic model that incorporates tumor microsatellite instability (MSI) information, called the AIFEG model, and in predicting the presence of mutations in MSH2 and MLH1 in probands with suspected hereditary non-polyposis colorectal cancer. The AIFEG model is based on published estimates of mutation frequencies and cancer penetrances in carriers and non-carriers and employs the program MLINK of the FASTLINK package to calculate the proband's carrier probability. Model performance is evaluated in a series of 219 families screened for mutations in both MSH2 and MLH1, in which 68 disease-causing mutations were identified. Predictions are first obtained using family history only and then converted into posterior probabilities using information on MSI. This improves predictions substantially. Using a probability threshold of 10% for mutation analysis, the AIFEG model applied to our series has 100% sensitivity and 71% specificity. C1 Univ Pisa, Ctr Stat Genet, Dept Expt Pathol, Pisa, Italy. IRCCS, Oncol Referral Ctr, Aviano, PN, Italy. Univ Modena, Dept Internal Med, I-41100 Modena, Italy. Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. Univ Verona, Dept Med Oncol, I-37100 Verona, Italy. Catholic Univ Rome, Inst Med Genet, Rome, Italy. Univ Florence, Dept Clin Pathophysiol, Florence, Italy. NHGRI, NIH, Baltimore, MD USA. RP Presciuttini, S (reprint author), CO Ctr Retrovirus, Ctr Stat Genet, SS Abetone & Brennero 2, I-56127 Pisa, Italy. EM sprex@biomed.unipi.it RI Ponz de Leon, Maurizio/A-9356-2015; Benatti, Piero/C-1052-2015; OI Ponz de Leon, Maurizio/0000-0003-4465-1043; Benatti, Piero/0000-0002-6826-1480; Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS NR 39 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2006 VL 69 IS 3 BP 254 EP 262 DI 10.1111/j.1399-004.2006.00577.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 019MI UT WOS:000235840300011 PM 16542391 ER PT J AU Brown, MW Singh, AK AF Brown, Michael W. Singh, Anurag K. TI Alkaline phosphatase level increase with initiation of hormone therapy for prostate cancer portends poor prognosis with rapid progression to bone metastases: A case report and review of the literature SO CLINICAL GENITOURINARY CANCER LA English DT Article DE bicalutamide; chemotherapy; leuprorelin acetate; prostate-specific antigen ID DISEASE; SERUM; MEN; ORCHIECTOMY; FLARE; ASSAY AB A 73-year-old man with localized prostate cancer was treated with androgen deprivation and radiation therapy. Staging evaluation showed no evidence of metastatic disease. After initiation of androgen deprivation therapy, the patient developed a marked increase in serum alkaline phosphatase (ALP). Despite continuation of hormonal ablation and completion of radiation therapy, ALP and prostate -specific antigen levels continued to increase. Bone metastases were documented 6 months after diagnosis. In this report, we explore the role of serum ALP as an indicator for patients who develop early metastases and thus might benefit from early initiation of aggressive secondary treatments such as chemotherapy. C1 Natl Canc Inst, Radiat Oncol Branch, NIH, CRC, Bethesda, MD 20892 USA. RP Singh, AK (reprint author), Natl Canc Inst, Radiat Oncol Branch, NIH, CRC, Bldg 10,B2 3500,10 Ctr Dr, Bethesda, MD 20892 USA. EM singan@mail.nih.gov NR 12 TC 2 Z9 3 U1 1 U2 4 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2006 VL 4 IS 4 BP 293 EP 295 DI 10.3816/CGC.2006.n.010 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LG UT WOS:000242526800010 PM 16729914 ER PT J AU Beekman, KW Colevas, AD Cooney, K DiPaola, R Dunn, RL Gross, M Keller, ET Pienta, KJ Ryan, CJ Smith, D Hussain, M AF Beekman, Kathleen W. Colevas, A. Dimitrios Cooney, Kathleen DiPaola, Robert Dunn, Rodney L. Gross, Mitchell Keller, Evan T. Pienta, Kenneth J. Ryan, Charles J. Smith, David Hussain, Maha TI Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer: Scientific rationale and study design SO CLINICAL GENITOURINARY CANCER LA English DT Article DE angiogenesis; EMD121974; hormone-refractory disease; NSC 707544; prostate-specific antigen ID CIRCULATING TUMOR-CELLS; INTEGRIN ALPHA(V)BETA(3); EPITHELIAL-CELLS; CLINICAL-TRIALS; EXPRESSION; BONE; ANGIOGENESIS; PROGRESSION; SURVIVAL; ANTIGEN AB Two randomized trials demonstrated an improvement in survival with docetaxel-based chemotherapy for patients with metastatic, androgenindependent prostate disease. However, the effect of current therapy is suboptimal in that it is complicated by toxicities and has no curative potential. Cilengiticle (EMD121974; NSC 707544), is a potent selective alpha nu beta 3 and alpha nu beta 5 integrin antagonist. Integrins are cell surface receptors that mediate a variety of cell activities including endothelial cell proliferation and migration. Blocking the ligation of integrins by antagonists promotes apoptosis of proliferative angiogenic cells, thereby suspending new blood vessel formation, which is essential for the growth of malignant disease, In prostate cancer specifically, integrins are known to be involved in metastases with differential expression on tumor cells. Tumors and vascular endothelial cells produce factors, such as vascular endothelial growth factor and basic fibroblast growth factor, that promote neovascularization, which has been implicated in prostate cancer progression. Cilengitide has been shown to inhibit ctvp3- and avp5-mediated cell adhesion and block in vitro enclothelial cell migration. In vivo experiments demonstrated that cilengitide inhibited cytoki ne- induced basic fibroblast growth factor- and vascular enclothelial growth factor-mediated angiogenesis in a dose-dependent manner. Cilengiticle also inhibited tumor growth in various in vivo systems. Two Cancer Therapy Evaluation Program-sponsored, multicenter, phase 11 trials are designed to evaluate the safety and efficacy of this agent in patients with androgen-independent prostate cancer. National Cancer Institute trial 6735 is evaluating cilengitide at.2000 mg in patients with nonmetastatic androgen-independent prostate cancer, and National Cancer Institute trial 6372 is evaluating 2 dose levels of cilengiticle, 500 mg or 2000 mg, intravenously twice weekly in patients with metastatic prostate cancer. C1 Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Div Hematol Oncol,Genitourinary Oncol Serv, Ann Arbor, MI 48109 USA. Natl Canc Inst, Invest Drug Branch, Therapy Evaluat Program, Rockville, MD USA. Canc Inst New Jersey, New Brunswick, NJ USA. Louis Warschaw Prostate Canc Ctr, Los Angeles, CA USA. Univ Michigan, Ctr Comprehens Canc, Dept Urol, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Hussain, M (reprint author), Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Div Hematol Oncol,Genitourinary Oncol Serv, 1500 E Med Ctr Dr,7303 CCGC-0946, Ann Arbor, MI 48109 USA. EM mahahuss@med.umich.edu RI Keller, Evan/M-1446-2016; Pienta, Kenneth/E-7679-2015 OI Keller, Evan/0000-0002-7592-7535; Pienta, Kenneth/0000-0002-4138-2186 FU NCI NIH HHS [5 P30 CA46592, P01 CA093900, P50CA69568] NR 21 TC 45 Z9 48 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD MAR PY 2006 VL 4 IS 4 BP 299 EP 302 DI 10.3816/CGC.2006.n.012 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LG UT WOS:000242526800012 PM 16729916 ER PT J AU Meky, FA Stoszek, SK Abdel-Hamid, M Selim, S Abdel-Wahab, A Mikhail, N El-Kafrawy, S El-Daly, M Abdel-Aziz, F Sharaf, S Mohamed, MK Engle, RE Emerson, SU Purcell, RH Fix, AD Strickland, GT AF Meky, FA Stoszek, SK Abdel-Hamid, M Selim, S Abdel-Wahab, A Mikhail, N El-Kafrawy, S El-Daly, M Abdel-Aziz, F Sharaf, S Mohamed, MK Engle, RE Emerson, SU Purcell, RH Fix, AD Strickland, GT TI Active surveillance for acute viral hepatitis in rural villages in the Nile delta SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACUTE SPORADIC HEPATITIS; E VIRUS; PHYLOGENETIC ANALYSIS; EGYPTIAN COMMUNITIES; UNITED-STATES; RISK-FACTORS; CAIRO; INFECTION; ADULTS; EPIDEMIOLOGY AB Background. Acute viral hepatitis is less frequent in Egypt than serum antibody levels suggest. Because acute viral hepatitis has a wide clinical spectrum, we tested the hypothesis that many cases are undetected because of mild illness caused by initial, early-childhood exposure to hepatitis viruses. Methods. During active case detection among 20,000 inhabitants of rural villages in Egypt, we screened 1715 symptomatic patients for serum alanine aminotransferase (ALT) levels. Viral hepatitis markers were tested in 47 subjects who had ALT levels that were least twice the normal level. Results. Of the 47 individuals tested, 4 children aged 3-5 years had immunoglobulin M (IgM) antibodies to hepatitis A virus (anti-HAV IgM). One also had a possible false-positive result to a test for IgM antibodies to hepatitis E virus. None had serological evidence of acute hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection. However, 33 of the remaining 43 had active HCV infection, having both antibodies to HCV (anti-HCV) and HCV RNA. Four others anti-HCV without HCV RNA, and 2 others had seroconversion to anti-HCV during follow-up. Two patients who were positive for hepatitis B surface antigen had chronic HBV infection. Only 3 with elevated ALT levels had no evidence of acute or chronic infections with known hepatitis viruses. Immunoglobulin G antibodies to hepatitis E virus was detected in 40 patients. Conclusion. Active surveillance covering similar to 50,000 person-years detected only 4 cases of acute HAV infection. Almost all persons with mild symptoms and elevated ALT levels had serological evidence of chronic viral hepatitis, most often associated with HCV. Many of these cases were probably "flare-ups" of HCV infection or incidental illness in patients with chronic HCV infection, but some could have been caused by difficult-to-confirm initial HCV infections. Although serological evidence for exposures was highly prevalent, hepatitis viruses seldom caused acute viral hepatitis in these communities. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Int Hlth Div, Washington, DC 20201 USA. Ain Shams Univ, Dept Community Environm & Occupat Med, Cairo, Egypt. Natl Hepatol & Trop Med Res Inst, Cairo, Egypt. Natl Liver Inst, Shibin El Kom, Egypt. Ctr Field & Appl Res, Qalyub, Egypt. NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Strickland, GT (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Int Hlth Div, 60 W Redwood St,Ste 100, Washington, DC 20201 USA. EM tstrick@epi.umaryland.edu RI El-Daly, Mai/C-4704-2013 FU NIAID NIH HHS [5U01AI058372-05] NR 27 TC 32 Z9 33 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2006 VL 42 IS 5 BP 628 EP 633 DI 10.1086/500133 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 008SE UT WOS:000235060200008 PM 16447107 ER PT J AU Birbaumer, N AF Birbaumer, N TI Brain-computer-interface research: Coming of age SO CLINICAL NEUROPHYSIOLOGY LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; SLOW CORTICAL POTENTIALS; MENTAL PROSTHESIS; COMMUNICATION; DEVICE; SYSTEM; CORTEX; BCI C1 NIH, Human Cort Physiol Unit, Bethesda, MD 20892 USA. Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Univ Trent, Ctr Cognit Neurosci, I-38100 Trento, Italy. RP Birbaumer, N (reprint author), NIH, Human Cort Physiol Unit, Bethesda, MD 20892 USA. EM niels.birbaumer@uni-tuebingen.de NR 37 TC 98 Z9 101 U1 0 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAR PY 2006 VL 117 IS 3 BP 479 EP 483 DI 10.1016/j.clinph.2005.11.002 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 029MR UT WOS:000236567700001 PM 16458595 ER PT J AU Southam-Gerow, MA Ringeisen, HL Sherrill, JT AF Southam-Gerow, MA Ringeisen, HL Sherrill, JT TI Integrating interventions and services research: Progress and prospects SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Editorial Material DE mental health research in primary care; organizational factors; patient preferences; services research; treatment research; usual care ID CLINICAL-TRIALS; ADOLESCENT PSYCHOTHERAPY; MENTAL-DISORDERS; CHILD; EFFICACY; PREVALENCE; THERAPIES; PATTERNS; MODEL AB Although intervention and services research paradigms have distinct historical roots and methodologic traditions, both aim to improve mental health services for adults and youth. This article introduces a series of articles that represent examples of innovative and integrative (i.e., integration of services and interventions research) research efforts. This work involves an integration of the intervention and services research paradigms to address the difficult questions related to improving mental health services in diverse settings. Each of the four articles takes a distinctly different path in bringing together the intervention and services research traditions, with foci ranging from (a) using psychotherapy measurement tools to assess the content of usual care practice in collaboration with providers, (b) adapting randomized clinical trial design to fit non-mental healthcare settings while addressing relevant outcomes, (c) understanding and incorporating patient preferences into treatment research, and (d) identifying organization-level variables relevant to intervention development and implementation. In the introductory article, we provide a brief precis concerning the intervention and services research traditions, highlight how each of the four articles illustrates an innovative integration of intervention and services research, and discuss additional future directions beyond the work introduced in this series. C1 Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. NIMH, Bethesda, MD 20892 USA. RP Southam-Gerow, MA (reprint author), Virginia Commonwealth Univ, Dept Psychol, 808 W Franklin St Box 842018, Richmond, VA 23284 USA. EM masouthamger@vcu.edu NR 38 TC 27 Z9 27 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SPR PY 2006 VL 13 IS 1 BP 1 EP 8 DI 10.1111/j.1468-2850.2006.00001.x PG 8 WC Psychology, Clinical SC Psychology GA 014HL UT WOS:000235470300001 ER PT J AU Floel, A Cohen, LG AF Floel, Agnes Cohen, Leonardo G. TI Translational studies in neurorehabilitation: From bench to bedside SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Review DE neuroplasticity; stroke; somatosensory stimulation; transcranial magnetic stimulation; direct current stimulation; dopamine; amphetamine AB Stroke is the leading cause of adult disability in the western world. Consensus has built over the last few years regarding the usefulness of training to improve motor disability resulting from stroke. Until recently, there were no accepted strategies to enhance the beneficial effects of training. However, the combination of basic and clinical science data over the last few years is changing this picture, and is highly relevant to the field of neurorehabiliation. Human studies in both healthy individuals and patients after brain damage demonstrate as a proof of principle that somatosensory input, cortical stimulation, interhemispheric interactions, and pharmacologic interventions can modulate cortical plasticity in neurorehabilitation after stroke. These findings strongly suggest directions in the development of novel strategies to enhance training effects on motor recovery. The intent of this review is to describe these strategies, the basic science principles on which they are based, and the clinical applications that have emerged so far. C1 Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Floel, Agnes/A-9426-2017 NR 142 TC 21 Z9 21 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD MAR PY 2006 VL 19 IS 1 BP 1 EP 10 DI 10.1097/00146965-200603000-00001 PG 10 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA V44FU UT WOS:000202989400001 PM 16633014 ER PT J AU Fowler, DH AF Fowler, DH TI Shared biology of GVHD and GVT effects: Potential methods of separation SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE allogeneic hematopoietic stem cell transplantation; immunotherapy; T lymphocytes ID GRAFT-VERSUS-HOST; BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CYTOTOXIC T-LYMPHOCYTES; MINOR HISTOCOMPATIBILITY ANTIGENS; NECROSIS-FACTOR-ALPHA; CHRONIC MYELOID-LEUKEMIA; INTERLEUKIN-1 RECEPTOR ANTAGONIST; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LEUKOCYTE INFUSIONS AB The difficult separation of clinical graft-versus-tumor (GVT) effects from graft-versus-host disease (GVHD) reflects their shared biology. Experimental approaches to mediate GVT effects while limiting GVHD include: (1) allograft T cell depletion followed by immune enhancement; (2) modulation of T cell dose or T cell subset composition; (3) donor lymphocyte infusion; (4) reduced-intensity host preparation; (5) modulation of Th1/Th2 and Tc1/Tc2 cell balance; (6) cytokine therapy or neutralization; (7) T regulatory cell therapy; (8) co-stimulatory pathway modulation; (9) chemokine pathway modulation; (10) induction of antigen-specific T cells; (11) alloreactive NK cell therapy; and (12) targeted pharmaceutical inhibition of proteosome, mammalian target of rapamycin, and histone deacetylase pathways. Clearly, a multitude of approaches exist that hold promise for separating GVT effects from GVHD. Future success in this endeavor will require a strong commitment towards translational research and continued advances in cell, vaccine, cytokine, monoclonal antibody, and targeted molecular therapy. Published by Elsevier Ireland Ltd. C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, East Labs 3,NIH, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, East Labs 3,NIH, 9000 Rockville Pike,3-3330, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov NR 312 TC 43 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAR PY 2006 VL 57 IS 3 BP 225 EP 244 DI 10.1016/j.critrevonc.2005.07.001 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 019TB UT WOS:000235858500003 PM 16207532 ER PT J AU Newman, DJ Cragg, GM AF Newman, DJ Cragg, GM TI Natural products from marine invertebrates and microbes as modulators of antitumor targets SO CURRENT DRUG TARGETS LA English DT Review DE marine natural products; molecular targets; cancer; structural modification ID LARGE-SCALE SYNTHESIS; HISTONE-DEACETYLASE INHIBITORS; MICROTUBULE-STABILIZING AGENTS; ARYL-HYDROCARBON RECEPTOR; SPONGE KIRKPATRICKIA-VARIALOSA; COMPOUND LIBRARY DEVELOPMENT; MACROCYCLIC KETONE ANALOGS; PRACTICAL TOTAL-SYNTHESIS; LACTACYSTIN BETA-LACTONE; CYCLIN-DEPENDENT KINASES AB Over the last twenty-five to thirty years, exploration of the marine fauna and microbial flora has progressed from a random search by natural product chemists who liked to dive and wished to combine their hobby with their profession, to fully integrated programs of systemic investigation of the chemical agents elaborated by marine organisms of all phyla (as presumably defensive agents against predators) for their potential as leads to human-use drug candidates where the putative mechanisms have been identified as modulation of, and/or interaction with, potential molecular targets, rather than Just exhibiting general cytotoxicity. This review is not exhaustive but is meant to cover the highlights of such agents and is arranged on a (nominal) target basis rather than by organism or chemical class. C1 NCI, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Nat Prod Branch, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Nat Prod Branch, Frederick, MD 21702 USA. EM dn22a@nih.gov NR 291 TC 45 Z9 53 U1 0 U2 18 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD MAR PY 2006 VL 7 IS 3 BP 279 EP 304 DI 10.2174/138945006776054960 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 021EB UT WOS:000235965400005 PM 16515528 ER PT J AU Morozov, V Wawrousek, EF AF Morozov, V Wawrousek, EF TI Caspase-dependent secondary lens fiber cell disintegration in alpha A-/alpha B-crystallin double-knockout mice SO DEVELOPMENT LA English DT Article DE caspase 3; caspase 6; alpha A-crystallin; alpha B-crystallin; double knockout mice ID PROTECTIVE ACTIVITY; EPITHELIAL-CELLS; DROSOPHILA HSP27; APOPTOSIS; DIFFERENTIATION; EXPRESSION; PROTEINS; GENE; FIBROBLASTS; ACTIVATION AB alpha B-crystallin has been demonstrated, in tissue culture experiments, to be a caspase 3 inhibitor; however, no animal model studies have yet been described. Here, we show that morphological abnormalities in lens secondary fiber cells of alpha A-/alpha B-crystallin gene double knockout (DKO) mice are consistent with, and probably result from, elevated DEVDase and VEIDase activities, corresponding to caspase 3 and caspase 6, respectively. Immunofluorescence microscopy revealed an increased amount of caspase 6, and the active form of caspase 3, in specific regions of the DKO lens, coincident with the site of cell disintegration. TUNEL labeling illustrated a higher level of DNA fragmentation in the secondary fiber lens cells of DKO mice, compared with wild-type mice. Using a pull-down assay, we show interaction between caspase 6 and alpha A- but not alpha B-crystallin. These studies suggest that a-crystallin plays a role in suppressing caspase activity, resulting in retention of lens fiber cell integrity following degradation of mitochondria and other organelles, which occurs during the apoptosis-like pathway of lens cell terminal differentiation. C1 NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Morozov, V (reprint author), NEI, Lab Mol & Dev Biol, NIH, Bldg 7,7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. EM morozovv@nei.nih.gov RI Wawrousek, Eric/A-4547-2008 FU Intramural NIH HHS NR 25 TC 58 Z9 61 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 2006 VL 133 IS 5 BP 813 EP 821 DI 10.1242/dev.02262 PG 9 WC Developmental Biology SC Developmental Biology GA 027UX UT WOS:000236442300005 PM 16439475 ER PT J AU Meyer, SE Carlson, GA Wiggs, EA Ronsaville, DS Martinez, PE Klimes-Dougan, B Gold, PW Radke-Yarrow, M AF Meyer, SE Carlson, GA Wiggs, EA Ronsaville, DS Martinez, PE Klimes-Dougan, B Gold, PW Radke-Yarrow, M TI A prospective high-risk study of the association among maternal negativity, apparent frontal lobe dysfunction, and the development of bipolar disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CARD SORTING TEST; DORSOLATERAL PREFRONTAL CORTEX; POSITRON EMISSION TOMOGRAPHY; MANIC-DEPRESSIVE PARENT; PROSPECTIVE FOLLOW-UP; DIAGNOSTIC INTERVIEW; TEST-PERFORMANCE; AFFECTIVELY ILL; JUVENILE MANIA; MENTAL-HEALTH AB In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study. the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mother's functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for it mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed front the perspective of a vulnerability-stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait. C1 Cedars Sinai Med Ctr, Div Child & Adolescent Psychiat, Los Angeles, CA 90048 USA. Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. NIMH, Bethesda, MD 20892 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Meyer, SE (reprint author), Cedars Sinai Med Ctr, Div Child & Adolescent Psychiat, 8730 Alden Dr,Suite W110, Los Angeles, CA 90048 USA. EM stephanie.meyer@cshs.org FU Intramural NIH HHS NR 78 TC 20 Z9 20 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 2006 VL 18 IS 2 BP 573 EP 589 DI 10.1017/S0954579406060299 PG 17 WC Psychology, Developmental SC Psychology GA 033IJ UT WOS:000236840200013 PM 16600068 ER PT J AU Ikuzawa, M Shimizu, K Yasumasu, S Iuchi, I Shi, YB Ishizuya-Oka, A AF Ikuzawa, M Shimizu, K Yasumasu, S Iuchi, I Shi, YB Ishizuya-Oka, A TI Thyroid hormone-induced expression of a bZip-containing transcription factor activates epithelial cell proliferation during Xenopus larval-to-adult intestinal remodeling SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE intestinal remodeling; TH; bZip; electroporation; organ culture; Xenopus ID ACID-BINDING PROTEIN; IN-VIVO ANALYSIS; GENE-EXPRESSION; AMPHIBIAN METAMORPHOSIS; LAEVIS METAMORPHOSIS; CONNECTIVE-TISSUE; TAIL RESORPTION; RESPONSE GENES; STOMACH; PROGRAM AB In the intestine during amphibian metamorphosis, stem cells appear, actively proliferate, and differentiate into an adult epithelium analogous to the mammalian counterpart. To clarify the molecular mechanisms regulating this process, we focused on a bZip-containing transcription factor (TH/bZip). We previously isolated TH/bZip from the Xenopus intestine as one of the candidate genes involved in adult epithelial development. Northern blot and in situ hybridization analyses showed that the transient and region-dependent expression of TH/bZip mRNA correlates well with the growth of adult epithelial primordia originating from the stem cells throughout the Xenopus intestine. To investigate its role in the adult epithelial development, we established an in vitro gene transfer system by using electroporation and organ culture techniques, and we overexpressed TH/bZip in the epithelium of Xenopus tadpole intestines. In the presence of thyroid hormone (TH) where the adult epithelial primordia appeared after 3 days of cultivation, overexpression of TH/bZip significantly increased their proliferating activity. On the other hand, in the absence of TH where the epithelium remained as larval-type without any metamorphic changes, ectopic expression of TH/bZip significantly increased the proliferating activity of the larval epithelium but had no effects on its differentiated state. These results indicate that TH/bZip functions as a growth activator during amphibian intestinal remodeling, although TH/bZip expression in the epithelium alone is not sufficient for inducing the stem cells. C1 Nippon Med Coll, Dept Biol, Kawasaki Ku, Kanagawa 2110063, Japan. Sophia Univ, Inst Life Sci, Chiyoda Ku, Tokyo 1028554, Japan. Hiroshima Prefectural Inst Ind Sci & Technol, CLUSTER, Yoshizato Project, Hiroshima 7390046, Japan. NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Ishizuya-Oka, A (reprint author), Nippon Med Coll, Dept Biol, Kawasaki Ku, Kanagawa 2110063, Japan. EM a-oka@nms.ac.jp FU Intramural NIH HHS NR 37 TC 8 Z9 9 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD MAR PY 2006 VL 216 IS 3 BP 109 EP 118 DI 10.1007/s00427-005-0037-4 PG 10 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 015IX UT WOS:000235546200001 PM 16292540 ER EF