FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Genedani, S Guidolin, D Leo, G Filaferro, M Torvinen, M Woods, AS Fuxe, K Ferre, S Agnati, LF AF Genedani, S Guidolin, D Leo, G Filaferro, M Torvinen, M Woods, AS Fuxe, K Ferre, S Agnati, LF TI Computer-assisted image analysis of caveolin-1 involvement in the internalization process of adenosine A(2A)-dopamine D-2 receptor heterodimers SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE adenosine A(2A) receptor; dopamine D; receptor; caveolin-1; heteromers; internalization ID DOPAMINE-D-2 RECEPTORS; PARKINSONS-DISEASE; ADENYLYL-CYCLASE; A(2A) RECEPTORS; D2; HETEROMERIZATION; COLOCALIZATION; ENDOCYTOSIS; MECHANISMS; BRAIN AB A functional aspect of horizontal molecular networks has been investigated experimentally, namely the heteromerization between adenosine A(2A) and doparnine D-2 receptors and the possible role of caveolin-1 in the cotrafficking of these molecular complexes. This study has been carried out by means of computer-assisted image analysis procedure of laser images of membrane immunoreactivity of caveolin-1, A(2A), D-1, and D-2 receptors obtained in two clones of Chinese hamster ovary cells-one transfected with A(2A) and dopamine D, receptors and the other one with A(2A) and D-2 receptors. Cells were treated for 3 h with 10 mu M D-1 receptor agonist SKF 38393,50 mu M D-2-D-3 receptor agonist quinpirole, and 200 nM A(2A) receptor agonist CGS 21680. In A(2A)-D-1-cotransfected cells, caveolin-1 was found to colocalize with both A2A and D, receptors and treatment with SKF 38393 induced internalization of caveolin-1 and D-1 receptors, with a preferential internalization of D, receptors colocalized. with caveolin-1. In A(2A)-D-2-cotransfected cells, caveolin-1 was found to colocalize with both A2A and D2 receptors and either CGS 21680 or quinpirole treatment induced internalization of caveolin-1 and A2A and D2 receptors, with a preferential internalization of A2A and D2 receptors colocalized with caveolin-1. The results suggest that A2A and D2 receptors and caveolin-1 likely interact forming a macrocomplex that internalizes upon agonist treatment. These observations are discussed in the frame of receptor oligomerization and of the possible functional role of caveolin-1 in the process of co-internalization and, hence, in controlling the permanence of receptors at the plasma membrane level (prerequisite for receptor mosaic organization and plastic adjustments) and in the control of receptor desensitization. C1 Univ Modena, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy. Univ Modena, Pharmacol Sect, I-41100 Modena, Italy. Univ Padua, Dept Human Anat & Physiol, Sect Anat, I-35121 Padua, Italy. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, Stockholm, Sweden. NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Agnati, LF (reprint author), Univ Modena, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy. EM agnati@tin.it RI Ferre, Sergi/K-6115-2014; Genedani, Susanna/K-4370-2016; OI Ferre, Sergi/0000-0002-1747-1779; Genedani, Susanna/0000-0003-1526-153X; Guidolin, Diego/0000-0003-2133-3552 NR 39 TC 27 Z9 27 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 177 EP 184 DI 10.1385/JMN/26:02:177 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800009 PM 16012191 ER PT J AU Agnati, LF Tarakanov, AO Ferre, S Fuxe, K Guidolin, D AF Agnati, LF Tarakanov, AO Ferre, S Fuxe, K Guidolin, D TI Receptor-receptor interactions, receptor mosaics, and basic principles of molecular network organization - Possible implications for drug development SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE receptor-receptor interactions; receptor mosaics; molecular networks; cooperativity ID CENTRAL-NERVOUS-SYSTEM; PROTEIN-COUPLED RECEPTORS; BETA-ADRENERGIC RECEPTORS; HIERARCHICAL ORGANIZATION; NEGATIVE COOPERATIVITY; HYPOTHESIS; MEMBRANE; BINDING; MODEL; OLIGOMERIZATION AB The phenomenon of receptor-receptor interactions was hypothesized by Agnati and Fuxe in the 1980s, and several indirect proofs were provided in the following years by means of in vitro binding experiments and in vivo experiments in physiological and pathological animal models. This paper aims to outline some of the most important features and consequences of this phenomenon in the frame of the structural and functional aspects of molecular networks. In particular, the concepts of receptor mosaic (RM), and of horizontal and vertical molecular networks (HMNs, VMNs, respectively) are illustrated. To discuss some aspects of the functional organization of molecular networks, not only new data on protein-protein interactions but also the biochemical mechanism of cooperativity will be used. On this basis, some theoretical deductions can be drawn that allow a tentative classification of the RMs and the proposal of the extension of the concept of branching point introduced for enzymes to the possible switching role of some RMs in directing signals to various VMNs. Finally, the cooperativity phenomenon and the so-called symmetry rule will be used to introduce a proper mathematical approach that characterizes RMs as to their receptor composition, receptor topography, and order of receptor activation inside the RM. These new data on G protein-coupled receptors and molecular network organization indicate possible new approaches for drug development. C1 Univ Modena, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy. Russian Acad Sci, St Petersburg Inst Informat & Automat, St Petersburg 196140, Russia. NIDA, Behav Neurosci Branch, NIH, DHHS, Bethesda, MD 20817 USA. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, S-17177 Stockholm, Sweden. Univ Padua, Dept Anat & Physiol, Padua, Italy. RP Agnati, LF (reprint author), Univ Modena, Physiol Sect, Dept Biomed Sci, I-41100 Modena, Italy. EM agnati@tin.it RI Ferre, Sergi/K-6115-2014; OI Ferre, Sergi/0000-0002-1747-1779; Fuxe, Kjell/0000-0001-8491-4288; Guidolin, Diego/0000-0003-2133-3552 NR 64 TC 54 Z9 54 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 193 EP 208 DI 10.1385/JMN/26:02:193 PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800011 PM 16012193 ER PT J AU Fuxe, K Ferre, S Canals, M Torvinen, M Terasmaa, A Marcellino, D Goldberg, SR Staines, W Jacobsen, KX Lluis, C Woods, AS Agnati, LF Franco, R AF Fuxe, K Ferre, S Canals, M Torvinen, M Terasmaa, A Marcellino, D Goldberg, SR Staines, W Jacobsen, KX Lluis, C Woods, AS Agnati, LF Franco, R TI Adenosine A(2A) and dopamine D-2 heteromeric receptor complexes and their function SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE adenosine A(2A) receptors; dopamine D-2 receptors; heteromers; Parkinson's disease; schizophrenia ID BIOLUMINESCENCE ENERGY-TRANSFER; A(2A) RECEPTORS; PARKINSONS-DISEASE; INTEGRATIVE MECHANISM; D-3 RECEPTOR; RAT STRIATUM; QUANTITATIVE ASSESSMENT; ADENYLYL-CYCLASE; BASAL GANGLIA; D2 RECEPTORS AB The existence of A(2A)-D-2 heteromeric complexes is based on coimmunoprecipitation studies and on fluorescence resonance energy transfer and bioluminescence resonance energy transfer analyses. It has now become possible to show that A(2A) and D-2 receptors also coimmunoprecipitate in striatal tissue, giving evidence for the existence of A(2A)-D-2 heteromeric receptor complexes also in rat striatal tissue. The analysis gives evidence that these heteromers are constitutive, as they are observed in the absence of A(2A) and D-2 agonists. The A(2A)-D-2 heteromers, could either be A(2A)-D-2 heterodimers and/or higher-order A(2A)-D-2 hetero-oligomers. In striatal neurons there are probably A(2A)-D-2 heteromeric complexes, together with A(2A)-D-2 homomeric complexes in the neuronal surface membrane. Their stoichiometry in various microdomains will have a major role in determining A(2A) and D-2 signaling in the striatopallidal GABA neurons. Through the use of D-2/D-1 chimeras, evidence has been obtained that the fifth transmembrane (TM) domain and/or the I3 of the D2 receptor are part of the A(2A)-D-2 receptor interface, where electrostatic epitope-epitope interactions involving the N-terminal part of I3 of the D-2 receptor (arginine-rich epitope) play a major role, interacting with the carboxyl terminus of the A(2A) receptor. Computerized modeling of A(2A)-D-2 heteromers are in line with these findings. It seems likely that A(2A) receptor-induced reduction of D-2 receptor recognition, G protein coupling, and signaling, as well as the existence of A(2A)-D-2 co-trafficking, are the consequence of the existence of an A(2A)-D-2 receptor heteromer. The relevance of A(2A)-D-2 heteromeric receptor complexes for Parkinson's disease and schizophrenia is emphasized as well as for the treatment of these diseases. Finally, recent evidence for the existence of antagonistic A(2A)-D-3 heteromeric receptor complexes in cotransfected cell lines has been summarized. C1 Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, Stockholm, Sweden. Univ Barcelona, Dept Biochem & Mol Biol, E-08007 Barcelona, Spain. Univ Ottawa, Ottawa, ON K1N 6N5, Canada. NIDA, DHHS, NIH, Intramural Res Program, Baltimore, MD 21224 USA. Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. RP Fuxe, K (reprint author), Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, Stockholm, Sweden. EM Kjell.Fuxe@neuro.ki.se RI Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Terasmaa, Anton/I-3312-2015; OI Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Terasmaa, Anton/0000-0002-5139-1764; Marcellino, Daniel/0000-0002-4618-7267; Staines, Willim/0000-0002-7288-5026; Fuxe, Kjell/0000-0001-8491-4288; Canals, Meritxell/0000-0002-7942-5006 NR 57 TC 120 Z9 121 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 209 EP 219 DI 10.1385/JMN/26:02:209 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800012 PM 16012194 ER PT J AU Franco, R Ciruela, F Casado, V Cortes, A Canela, EI Mallol, J Agnati, LF Ferre, S Fuxe, K Lluis, C AF Franco, R Ciruela, F Casado, V Cortes, A Canela, EI Mallol, J Agnati, LF Ferre, S Fuxe, K Lluis, C TI Partners for adenosine A(1) receptors SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE heteromer; dimer; G protein-coupled receptors; adenosine deaminase; glutamate; metabotroppic; scaffold; caveolin; brain ID CENTRAL-NERVOUS-SYSTEM; GLUTAMATE TYPE-1-ALPHA RECEPTOR; RAT CEREBRAL-CORTEX; T-CELL-ACTIVATION; A(1)-ADENOSINE RECEPTOR; SYNERGISTIC INTERACTION; PRESYNAPTIC INHIBITION; SYNAPTIC TRANSMISSION; MEDIATED MODULATION; GUANINE-NUCLEOTIDE AB G protein-coupled receptors (GPCRs) are targets for therapy in a variety of neurological diseases. Using adenosine A(2) receptors (A(1)Rs) as paradigm of GPCRs, this review focuses on how protein-protein interactions from monomers to heteromers, can contribute to hormone/neurotransmitter/neuromodulator regulation. The interaction of A(1)Rs with other membrane receptors, enzymes, and adaptor and scaffolding proteins is relevant for receptor traffic, internalization, and desensitization, and A(1)Rs are extremely important in driving signaling through different intracellular pathways. There is even the possibility of linking together GPCR heteromeric complexes with ion channel receptors in a receptor mosaic that might have special integrative value and might constitute the molecular basis for learning and memory. C1 Univ Barcelona, Dept Biochem & Mol Biol, E-08007 Barcelona, Spain. Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Franco, R (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, E-08007 Barcelona, Spain. EM rfranco@ub.edu RI Marion-Poll, Frederic/D-8882-2011; Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Marion-Poll, Frederic/0000-0001-6824-0180; Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 NR 71 TC 14 Z9 14 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 221 EP 231 DI 10.1385/JMN/26:02:221 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800013 PM 16012195 ER PT J AU Ciruela, F Canela, L Burgueno, J Soriguera, A Cabello, N Canela, EI Casado, V Cortes, A Mallol, J Woods, AS Ferre, S Lluis, C Franco, R AF Ciruela, F Canela, L Burgueno, J Soriguera, A Cabello, N Canela, EI Casado, V Cortes, A Mallol, J Woods, AS Ferre, S Lluis, C Franco, R TI Heptaspanning membrane receptors and cytoskeletal/scaffolding proteins - Focus on adenosine, dopamine, and metabotropic glutamate receptor function SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd Wenner-Gren International Symposium CY SEP 08-11, 2004 CL Stockholm, SWEDEN SP Wenner-Gren Fdn DE GPCR; adenosine; glutamate; dopamine; protein-protein interaction ID ACTIN-BINDING-PROTEIN; CELL-SURFACE EXPRESSION; PLASMA-MEMBRANE; NMDA-RECEPTOR; DENDRITIC SPINES; ALPHA-ACTININ; POSTSYNAPTIC DENSITY; ERYTHROCYTE-MEMBRANE; RAT HIPPOCAMPUS; PDZ DOMAIN AB Most cellular functions are mediated by multiprotein complexes. In neurons, these complexes are directly involved in the proper neuronal transmission, which is responsible for phenomena like learning, memory and development. In recent years studies based on two-hybrid screens and proteomic, biochemical, and cell biology approaches have shown that intracellular domains of G protein-coupled receptors (GPCRs) or heptaspanning membrane receptors (HSMRs) interact with intracellular proteins. These interactions are the basis of a protein network associated with these receptors, which includes scaffolding proteins containing one or several PDZ (post-synaptic-density-95 /discs-large/zona occludens-1) domains, signaling proteins, and proteins of the cytoskeleton. The present article is focused on the emerging evidence for interactions of adenosine, dopamine, and metabotropic glutamate receptors, with scaffolding and cytoskeletal proteins that play a role in the targeting and anchoring of these receptors to the plasma membrane, thus contributing to neuronal development and plasticity. Finally, given the complexity of neurological disorders such as ischemic stroke, Alzheimer's disease, and epilepsy, exploitation of these HSMR-associated interactions might prove to be efficient in the treatment of such disorders. C1 Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. Target Validat, Lab Dr Esteve, Barcelona 08028, Spain. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ciruela, F (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. EM fciruela@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 NR 159 TC 17 Z9 18 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PY 2005 VL 26 IS 2-3 SI SI BP 277 EP 292 DI 10.1385/JMN/26:02:277 PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 944FU UT WOS:000230412800019 PM 16012201 ER PT J AU Agnati, LF Genedani, S Lenzi, PL Leo, G Mora, F Ferre, S Fuxe, K AF Agnati, LF Genedani, S Lenzi, PL Leo, G Mora, F Ferre, S Fuxe, K TI Energy gradients for the homeostatic control of brain ECF composition and for VT signal migration: introduction of the tide hypothesis SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article; Proceedings Paper CT 20th Biennial Meeting of the International-Society-for-Neurochemistry/European-Society-for-Neurochemi stry CY AUG 21-26, 2005 CL Innsbruck, AUSTRIA SP Int Soc Neurochem, European Soc Neurochem DE tide hypothesis; volume transmission; brain ECF homeostasis; evolution "tinkering" ID CENTRAL-NERVOUS-SYSTEM; VOLUME TRANSMISSION; UNCOUPLING PROTEIN-2; FLUID-FLOW; RAT-BRAIN; TEMPERATURE; COMMUNICATION; RECEPTORS; PRESSURE; CHANNELS AB The present paper enlightens a new point of view on brain homeostasis and communication, namely how the brain takes advantage of different chemical-physical phenomena such as pressure waves, and temperature and concentration gradients to allow the renewal of the extra-cellular fluid (i.e., the homeostasis of the brain internal milieu) as well as some forms of intercellular communications (Volume Transmission) at an energy cost much lower than the classical synaptic transmission (the prototype of Wiring Transmission). In particular, the possible functional meaning of the intracranial pressure waves is discussed in the frame of the so called "tide hypothesis" which maintains that the pressure waves, created by the cardiac pump, modulate the cerebro-spinal fluid flow from and towards the subarachnoid space as well as towards and from the Virchow-Robin spaces. These fluid push-pull movements favor both the migration of signals and the extra-cellular fluid renewal, especially in the cerebral cortex. C1 Univ Modena & Reggio Emilia, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Dept Biomed Sci, Pharmacol Sect, I-41100 Modena, Italy. Univ Bologna, Dept Physiol, I-40126 Bologna, Italy. Univ Complutense Madrid, Dept Physiol, E-28040 Madrid, Spain. NIDA, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Agnati, LF (reprint author), Univ Modena & Reggio Emilia, Dept Biomed Sci, Physiol Sect, Via Campi 287, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Ferre, Sergi/K-6115-2014; Genedani, Susanna/K-4370-2016; OI Ferre, Sergi/0000-0002-1747-1779; Genedani, Susanna/0000-0003-1526-153X; Fuxe, Kjell/0000-0001-8491-4288 NR 54 TC 25 Z9 25 U1 0 U2 0 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD JAN PY 2005 VL 112 IS 1 BP 45 EP 63 DI 10.1007/s00702-004-0180-5 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 888JC UT WOS:000226369200004 PM 15599604 ER PT J AU Agnati, LF Genedani, S Rasio, G Galantucci, M Saltini, S Filaferro, M Franco, R Mora, F Ferre, S Fuxe, K AF Agnati, LF Genedani, S Rasio, G Galantucci, M Saltini, S Filaferro, M Franco, R Mora, F Ferre, S Fuxe, K TI Studies on homocysteine plasma levels in Alzheimer's patients. Relevance for neurodegeneration SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article; Proceedings Paper CT 20th Biennial Meeting of the International-Society-for-Neurochemistry/European-Society-for-Neurochemi stry CY AUG 21-26, 2005 CL Innsbruck, AUSTRIA SP Int Soc Neurochem, European Soc Neurochem DE homocysteine; Alzheimer disease; NMDA receptors; glycine receptors; intercellular communication ID RISK FACTOR; BRAIN; FOLATE AB Homocysteine (HC) may work inter alia as a Volume Transmission signal since HC is present in the brain and cerebrospinal fluid and binds to NMDA receptors. Furthermore, in cell cultures increased HC formation increases its export. In the present study we have shown that after intravenous injection in intact animals HC penetrates the blood-brain barrier. Hence, it works as a blood-born humoral signal. Furthermore, we have studied HC plasma levels in a group of Alzheimer's (AD) patients and compared with a group of age-matched patients. It has been confirmed that a positive correlation exists between age and HC plasma levels in the control group, but not in the AD patients. These results may depend on the fact that in AD patients high HC plasma levels (possibly associated with high glycine levels and/or excessive glutamate release) have favored neurodegeneration and, once this pathological process has been triggered off, the plasma HC levels become independent of the "physiological" aging-induced increase of HC plasma levels. C1 Univ Modena & Reggio Emilia, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Dept Biomed Sci, Pharmacol Sect, I-41100 Modena, Italy. Osped Nuovo Montecchi, Clin Chem Lab, Suzzara, Italy. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. Univ Complutense Madrid, Dept Physiol, E-28040 Madrid, Spain. NIDA, Dept Hlth & Human Serv, Baltimore, MD USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Agnati, LF (reprint author), Univ Modena & Reggio Emilia, Dept Biomed Sci, Physiol Sect, Via Campi 287, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Genedani, Susanna/K-4370-2016; OI Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Genedani, Susanna/0000-0003-1526-153X; Fuxe, Kjell/0000-0001-8491-4288 NR 19 TC 27 Z9 29 U1 0 U2 1 PU SPRINGER WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD JAN PY 2005 VL 112 IS 1 BP 163 EP 169 DI 10.1007/s00702-004-0154-7 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 888JC UT WOS:000226369200014 PM 15599614 ER PT J AU Raizer, JJ Koutcher, JA Abrey, LE Panageas, KS DeAngelis, LM Lis, E Xu, S Zakian, KL AF Raizer, JJ Koutcher, JA Abrey, LE Panageas, KS DeAngelis, LM Lis, E Xu, S Zakian, KL TI Proton magnetic resonance spectroscopy in immunocompetent patients with primary central nervous system lymphoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE magnetic resonance spectroscopy; primary central nervous system lymphoma ID PRIMARY CNS LYMPHOMA; HUMAN BRAIN-TUMORS; RECURRENT MALIGNANT GLIOMAS; MR-SPECTROSCOPY; IN-VIVO; RADIATION-THERAPY; RADIOTHERAPY; DIAGNOSIS; LESIONS; DIFFERENTIATION AB Background: Magnetic resonance spectroscopy imaging (MRSI) non-invasively evaluates the metabolic profile of normal and abnormal brain tissue. Primary central nervous system lymphoma (PCNSL) is a highly aggressive tumor responsive to high-dose methotrexate based regimens. Patients often have complete responses but relapses are common. We characterized the MR spectra of PCNSL patients, correlated MRSI with MRI and evaluated whether early recurrence could be detected by MRSI. Methods: Patients with PCNSL had multi-voxel MRSI before, during, and after treatment. The region of interest was defined using axial FLAIR images. Metabolites assessed were N-acetyl-aspartate (NAA), choline (Cho), creatine (Cr), lipid, and lactate. Ratios of Cho/Cr, NAA/Cho, and NAA/Cr were calculated and correlated with MRI. Overall survival (OS), progression free survival (PFS), and relative risks of each of the ratios were determined. Results: MRSI was performed on 11 men and seven women; median age of 59. Sixty-seven MRSI studies were performed, 17 baseline and 48 follow-up studies. Median ratios in 16 pretreated patients were Cho/Cr-1.90, NAA/ Cho-0.39, and NAA/Cr-1.27. Two patients had lipid at baseline five had lactate and two had both. MRSI correlated with tumor response or progression on MRI; in three patients MRSI suggested disease progression prior to changes on MRI. Univariate analysis of metabolite ratios, lipid, and lactate revealed that none significantly affected PFS or OS. Kaplan-Meier analysis of the presence or absence of lipid, lactate or both revealed a trend for increased PFS. Conclusion: MRSI and MRI correlate with tumor response or progression and may allow early detection of disease recurrence. The presence or absence of lipid and/ or lactate may have prognostic significance. Further research using MRSI needs to be done to validate our findings and determine the role of MRSI in PCNSL. C1 Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA. Mem Sloan Kettering Canc Ctr, Dept Med Phys Radiol & Med, Bronx, NY USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, Bronx, NY USA. Mem Sloan Kettering Canc Ctr, Dept Biostat, Bronx, NY USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, Bronx, NY USA. Mem Sloan Kettering Canc Ctr, NIMH, Unit Magnet Resonance Spect, Bronx, NY USA. Mem Sloan Kettering Canc Ctr, Dept Radiol & Med, Bronx, NY USA. RP Raizer, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Neurol, Room 1123,710 N Lake Shore Dr,Abbott Hall, Chicago, IL 60611 USA. EM jraizer@nmff.org NR 43 TC 23 Z9 31 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2005 VL 71 IS 2 BP 173 EP 180 DI 10.1007/s11060-004-1360-8 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 896NI UT WOS:000226940400015 PM 15690135 ER PT J AU Chaurasia, SS Rollag, MD Jiang, G Hayes, WP Haque, R Natesan, A Zatz, M Tosini, G Liu, C Korf, HW Iuvone, PM Provencio, I AF Chaurasia, SS Rollag, MD Jiang, G Hayes, WP Haque, R Natesan, A Zatz, M Tosini, G Liu, C Korf, HW Iuvone, PM Provencio, I TI Molecular cloning, localization and circadian expression of chicken melanopsin (Opn4): differential regulation of expression in pineal and retinal cell types SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE circadian; entrainment; melanopsin; photoreceptors; pineal; retina ID SEROTONIN N-ACETYLTRANSFERASE; MELATONIN RHYTHM; PHOTOENDOCRINE TRANSDUCTION; MESSENGER-RNA; PHOTORECEPTOR CELLS; SYNTHESIZING ENZYME; CONTACTING NEURONS; PHOTIC CONTROL; INNER RETINA; BLIND MICE AB The avian retina and pineal gland contain autonomous circadian oscillators and photo-entrainment pathways, but the photopigment(s) that mediate entrainment have not been definitively identified. Melanopsin (Opn4) is a novel opsin involved in entrainment of circadian rhythms in mammals. Here, we report the cDNA cloning of chicken melanopsin and show its expression in retina, brain and pineal gland. Like the melanopsins identified in amphibians and mammals, chicken melanopsin is more similar to the invertebrate retinaldehyde-based photopigments than the retinaldehyde-based photopigments typically found in vertebrates. In retina, melanopsin mRNA is expressed in cells of all retinal layers. In pineal gland, expression was strong throughout the parenchyma of the gland. In brain, expression was observed in a few discrete nuclei, including the lateral septal area and medial preoptic nucleus. The retina and pineal gland showed distinct diurnal expression patterns. In pineal gland, melanopsin mRNA levels were highest at night at Zeitgeber time (ZT) 16. In contrast, transcript levels in the whole retina reached their highest levels in the early morning (ZT 0-4). Further analysis of melanopsin mRNA expression in retinal layers isolated by laser capture microdissection revealed different patterns in different layers. There was diurnal expression in all retinal layers except the ganglion cell layer, where heavy expression was localized to a small number of cells. Expression of melanopsin mRNA peaked during the daytime in the retinal pigment epithelium and inner nuclear layer but, like in the pineal, at night in the photoreceptors. Localization and regulation of melanopsin mRNA in the retina and pineal gland is consistent with the hypothesis that this novel photopigment plays a role in photic regulation of circadian function in these tissues. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. NIMH, Sect Biochem Pharm, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Morehouse Sch Med, Inst Neurosci, Atlanta, GA 30310 USA. Univ Frankfurt, Inst Anat 2, D-6000 Frankfurt, Germany. RP Provencio, I (reprint author), Univ Virginia, Dept Biol, Room 281,Gilmer Hall,POB 400328, Charlottesville, VA 22904 USA. EM ip7m@virginia.edu OI tosini, gianluca/0000-0003-3645-4533 FU NEI NIH HHS [EY04864, R01 EY004864]; NIMH NIH HHS [MH62405]; NINDS NIH HHS [NS43459] NR 68 TC 111 Z9 112 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2005 VL 92 IS 1 BP 158 EP 170 DI 10.1111/j.1471-4159.2004.02874.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 878FN UT WOS:000225632200015 PM 15606905 ER PT J AU Thiel, G Al Sarraj, J Vinson, C Stefano, L Bach, K AF Thiel, G Al Sarraj, J Vinson, C Stefano, L Bach, K TI Role of basic region leucine zipper transcription factors cyclic AMP response element binding protein (CREB), CREB2, activating transcription factor 2 and CAAT/enhancer binding protein alpha in cyclic AMP response element-mediated transcription SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE activating transcription factor 2; cyclic AMP response element; cAMP response element binding protein; cAMP-dependent protein kinase; secretogranin II; tyrosine hydroxylase ID TYROSINE-HYDROXYLASE GENE; CATECHOLAMINERGIC IMMORTALIZED NEURON; CORTICOTROPIN-RELEASING-FACTOR; CAMP-SIGNALING PATHWAY; CATALYTIC SUBUNIT; DNA-BINDING; BIOLOGICAL-ACTIVITY; GROWTH-FACTOR; CELL-LINES; C-JUN AB The transcription factor cAMP response element binding protein (CREB), a member of the basic region leucine zipper (bZIP) family of proteins, is the major cAMP response element (CRE) binding. Other bZIP proteins, including CREB2, activating transcription factor 2 (ATF2), or CAAT/enhancer binding protein (C/EBP) have been reported to transactivate CRE-containing genes or to interfere with transactivation by CREB. We have designed a simple transactivation assay using expression of either a constitutively active CREB mutant or a nuclear targeted mutant of the catalytic subunit of cAMP-dependent protein kinase. In both cases, a striking stimulation of transcription of CRE-containing reporter genes was observed in noradrenergic locus coeruleus-like CATH.a cells. In addition, a constitutively active mutant of ATF2 specifically transactivated a secretogranin II promoter/luciferase reporter gene, but had no effect on the tyrosine hydroxylase promoter. In contrast, CREB2 and C/EBPalpha did not transactivate CRE-containing reporter genes, indicating that these bZIP proteins target distinct genetic elements. Experiments involving dominant-negative bZIP mutants revealed that CREB does not heterodimerize with CREB2, ATF2, c-Jun or C/EBP. Rather, CREB and ATF2 compete for binding to the CRE, and are independently able to up-regulate transcription of genes containing CRE motifs in their regulatory regions. C1 Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. RP Thiel, G (reprint author), Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, Bldg 44, D-66421 Homburg, Germany. EM gerald.thiel@uniklinik-saarland.de NR 64 TC 41 Z9 41 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2005 VL 92 IS 2 BP 321 EP 336 DI 10.1111/j.1471-4159.2004.02882.x PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 880LR UT WOS:000225791800011 PM 15663480 ER PT J AU Canals, M Angulo, E Casado, V Canela, EI Mallol, J Vinals, F Staines, W Tinner, B Hillion, J Agnati, L Fuxe, K Ferre, S Lluis, C Franco, R AF Canals, M Angulo, E Casado, V Canela, EI Mallol, J Vinals, F Staines, W Tinner, B Hillion, J Agnati, L Fuxe, K Ferre, S Lluis, C Franco, R TI Molecular mechanisms involved in the adenosine A(1) and A(2A) receptor-induced neuronal differentiation in neuroblastoma cells and striatal primary cultures SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE neuritogenesis; neuron; SH-SY5Y cells; signalling; TrkB ID PROTEIN-KINASE-C; INDUCED NEURITE OUTGROWTH; CENTRAL-NERVOUS-SYSTEM; PC12 CELLS; RETINOIC ACID; NEUROTROPHIC FACTOR; SIGNALING PATHWAYS; NUCLEUS-ACCUMBENS; ALZHEIMER-DISEASE; DOPAMINE RELEASE AB Adenosine A(1) receptors (A(1)Rs) and adenosine A(2A) receptors (A(2A)Rs) are the major mediators of the neuromodulatory actions of adenosine in the brain. In the striatum A(1)Rs and A(2A)Rs are mainly co-localized in the GABAergic striatopallidal neurons. In this paper we show that agonist-induced stimulation of A(1)Rs and A(2A)Rs induces neurite outgrowth processes in the human neuroblastoma cell line SH-SY5Y and also in primary cultures of striatal neuronal precursor cells. The kinetics of adenosine-mediated neuritogenesis was faster than that triggered by retinoic acid. The triggering of the expression of TrkB neurotrophin receptor and the increase of cell number in the G(1) phase by the activation of adenosine receptors suggest that adenosine may participate in early steps of neuronal differentiation. Furthermore, protein kinase C (PKC) and extracellular regulated kinase-1/2 (ERK-1/2) are involved in the A(1)R- and A(2A)R-mediated effects. Inhibition of protein kinase A (PKA) activity results in a total inhibition of neurite outgrowth induced by A(2A)R agonists but not by A(1)R agonists. PKA activation is therefore necessary for A(2A)R-mediated neuritogenesis. Co-stimulation does not lead to synergistic effects thus indicating that the neuritogenic effects of adenosine are mediated by either A1 or A(2A) receptors depending upon the concentration of the nucleoside. These results are relevant to understand the mechanisms by which adenosine receptors modulate neuronal differentiation and open new perspectives for considering the use of adenosine agonists as therapeutic agents in diseases requiring neuronal repair. C1 Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Univ Barcelona, Dept Ciencies Fisiol 2, E-08028 Barcelona, Spain. Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada. NINDS, NIH, US Dept HHS, Baltimore, MD USA. NIDA, NIH, US Dept HHS, Baltimore, MD USA. Univ Modena, Dept Biomed Sci, Physiol Sect, I-41100 Modena, Italy. Karolinska Inst, Dept Neurosci, Div Cellular & Mol Neurochem, Stockholm, Sweden. RP Franco, R (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, Marti Franques 1, E-08028 Barcelona, Spain. EM rfranco@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Staines, Willim/0000-0002-7288-5026; Canals, Meritxell/0000-0002-7942-5006; Casado, Vicent/0000-0002-1764-3825 NR 47 TC 35 Z9 35 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2005 VL 92 IS 2 BP 337 EP 348 DI 10.1111/j.1471-4159.2004.02856.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 880LR UT WOS:000225791800012 PM 15663481 ER PT J AU Monson, NL Brezinschek, HP Brezinschek, RI Mobley, A Vaughan, GK Frohman, EM Racke, MK Lipsky, PE AF Monson, NL Brezinschek, HP Brezinschek, RI Mobley, A Vaughan, GK Frohman, EM Racke, MK Lipsky, PE TI Receptor revision and atypical mutational characteristics in clonally expanded B cells from the cerebrospinal fluid of recently diagnosed multiple sclerosis patients SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE B lymphocytes; antibodies; autoimmunity; gene rearrangement ID HEAVY-CHAIN REPERTOIRE; CERVICAL LYMPH-NODES; SOMATIC HYPERMUTATION; IMMUNE-RESPONSE; SELECTIVE INFLUENCES; DISEASE PROGRESSION; PERIPHERAL-BLOOD; GERMINAL-CENTERS; DNA STRANDS; RGYW MOTIFS AB Purpose: to determine whether cerebrospinal fluid (CSF) B cells exhibit clonal expansion in patients recently diagnosed with multiple sclerosis (MS). CSF B cell clonal expansion was detected early in the disease process. Evidence of receptor revision was present in at least one MS patient who had been recently diagnosed with MS. Targeting of mutations to RGYW/WRCY motifs within CDRs was nominally observed in the CSF B cell clones despite the high mutational frequencies (MF). These observations are consistent with the presence of intense specific B cell stimulation and expansion in the CNS of MS patients early in the disease process. (C) 2004 Elsevier B.V. All rights reserved. C1 UT SW Med Ctr, Dept Neurol, Ctr Immunol, Dallas, TX 75390 USA. Univ Hosp Graz, Dept Internal Med, A-8036 Graz, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Racke, MK (reprint author), UT SW Med Ctr, Dept Neurol, Ctr Immunol, Dallas, TX 75390 USA. EM michael.racke@utsouthwestern.edu FU NIAID NIH HHS [R01 AI 47133]; NINDS NIH HHS [K24 NS 44250, R01 NS 37513, R01 NS 40993] NR 48 TC 51 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2005 VL 158 IS 1-2 BP 170 EP 181 DI 10.1016/j.jneuroim.2004.04.022 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 884KR UT WOS:000226084100021 PM 15589051 ER PT J AU Chen, JT Lin, YY Shan, DE Wu, ZA Hallett, M Liao, KK AF Chen, JT Lin, YY Shan, DE Wu, ZA Hallett, M Liao, KK TI Effect of transcranial magnetic stimulation on bimanual movements SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPPLEMENTARY MOTOR AREA; SUBJECTS MIMICKING TREMOR; PARKINSONS-DISEASE; REPETITIVE MOVEMENTS; SENSORIMOTOR CORTEX; FINGER MOVEMENT; TIME PERCEPTION; COORDINATION; ACTIVATION; INHIBITION AB Transcranial magnetic stimulation (TMS) of the motor cortex can interrupt voluntary contralateral rhythmic limb movements. Using the method of "resetting index" (RI), our study investigated the TMS effect on different types of bimanual movements. Six normal subjects participated. For unimanual movement, each subject tapped either the right or left index finger at a comfortable rate. For bimanual movement, index fingers of both hands tapped in the same (in-phase) direction or in the opposite (antiphase) direction. TMS was applied to each hemisphere separately at various intensities from 0.5 to 1.5 times motor threshold (MT). TMS interruption of rhythm was quantified by RI. For the unimanual movements, TMS disrupted both contralateral and ipsilateral rhythmic hand movements, although the effect was much less in the ipsilateral hand. For the bimanual in-phase task, TMS could simultaneously reset the rhythmic movements of both hands, but the effect on the contralateral hand was less and the effect on the ipsilateral hand was more compared with the unimanual tasks. Similar effects were seen from right and left hemisphere stimulation. TMS had little effect on the bimanual antiphase task. The equal effect of right and left hemisphere stimulation indicates that neither motor cortex is dominant for simple bimanual in-phase movement. The smaller influence of contralateral stimulation and the greater effect of ipsilateral stimulation during bimanual in-phase movement compared with unimanual movement suggest hemispheric coupling. The antiphase movements were resistant to TMS disruption, and this suggests that control of rhythm differs in the 2 tasks. TMS produced a transient asynchrony of movements on the 2 sides, indicating that both motor cortices might be downstream of the clocking command or that the clocking is a consequence of the 2 hemispheres communicating equally with each other. C1 Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, Taipei 11217, Taiwan. Natl Yang Ming Univ, Dept Neurol, Taipei 112, Taiwan. Cathay Gen Hosp, Dept Neurol, Taipei, Taiwan. NINDS, NIH, Bethesda, MD 20892 USA. RP Liao, KK (reprint author), Taipei Vet Gen Hosp, Neurol Inst, Dept Neurol, 201,Sect 2,Shih Pai Rd,Pei Tou Dist, Taipei 11217, Taiwan. EM kkliao@vghtpe.gov.tw NR 49 TC 17 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2005 VL 93 IS 1 BP 53 EP 63 DI 10.1152/jn.01063.2003 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 880GV UT WOS:000225777900006 PM 15331622 ER PT J AU Thompson, KG Bichot, NP Sato, TR AF Thompson, KG Bichot, NP Sato, TR TI Frontal eye field activity before visual search errors reveals the integration of bottom-up and top-down salience SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADE TARGET SELECTION; LATERAL INTRAPARIETAL AREA; SUPERIOR COLLICULUS; MACAQUE; NEURONS; TASK; CORTEX; ATTENTION; MOVEMENT; MODEL AB We investigated the saccade decision process by examining activity recorded in the frontal eye field (FEF) of monkeys performing 2 separate visual search experiments in which there were errors in saccade target choice. In the first experiment, the difficulty of a singleton search task was manipulated by varying the similarity between the target and distractors; errors were made more often when the distractors were similar to the target. On catch trials in which the target was absent the monkeys occasionally made false alarm errors by shifting gaze to one of the distractors. The second experiment was a popout color visual search task in which the target and distractor colors switched unpredictably across trials. Errors occurred most frequently on the first trial after the switch and less often on subsequent trials. In both experiments, FEF neurons selected the saccade goal on error trials, not the singleton target of the search array. Although saccades were made to the same stimulus locations, presaccadic activation and the magnitude of selection differed across trial conditions. The variation in presaccadic selective activity was accounted for by the variation in saccade probability across the stimulus - response conditions, but not by variations in saccade metrics. These results suggest that FEF serves as a saccade probability map derived from the combination of bottom-up and top-down influences. Peaks on this map represent the behavioral relevance of each item in the visual field rather than just reflecting saccade preparation. This map in FEF may correspond to the theoretical salience map of many models of attention and saccade target selection. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Thompson, KG (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM kgt@lsr.nei.nih.gov FU Intramural NIH HHS [Z01 EY000389-04]; NEI NIH HHS [R01-EY-08890, R01 EY008890, P30-EY-08126, P30 EY008126] NR 47 TC 81 Z9 81 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2005 VL 93 IS 1 BP 337 EP 351 DI 10.1152/jn.00330.2004 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 880GV UT WOS:000225777900030 PM 15317836 ER PT J AU Khan, NW Kondo, M Hiriyanna, KT Jamison, JA Bush, RA Sieving, PA AF Khan, NW Kondo, M Hiriyanna, KT Jamison, JA Bush, RA Sieving, PA TI Primate retinal signaling pathways: Suppressing ON-pathway activity in monkey with glutamate analogues mimics human CSNB1-NYX genetic night blindness SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID SCOTOPIC THRESHOLD RESPONSE; X-LINKED RETINOSCHISIS; SOURCE DENSITY ANALYSIS; BIPOLAR CELLS; B-WAVE; HORIZONTAL CELLS; MACAQUE RETINA; GANGLION-CELLS; FLICKER ERG; CAT RETINA AB Retinal ON-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram ( ERG) recordings elicited with photopic sinusoidal and rapid-ON/OFF-ramp flicker stimuli that are reputed to elicit ON/OFF-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal ON- or OFF-pathway bipolar cell activity. 2-amino-4-phosphonobutyric acid (APB), which selectively blocks light responses of ON- pathway depolarizing bipolar cells, fully recreated the essential ERG abnormalities found for human CSNB1 under the condition that the OFF-pathway remained active. Both CSNB1-NYX humans and APB-treated monkey retina lacked the normal amplitude dip and the phase deflection that occurs in the fundamental component near 12 Hz for sinusoidal flicker stimuli. The OFF-pathway suppressing agent, cis-2,3-piperidine-dicarboxylic acid (PDA), gave results in monkey quite discordant to CSNB1 human for sinusoidal stimulation. The results implicated a specific ON- pathway signaling deficiency in CSNB1-NYX males with no evidence of OFF-pathway involvement. Likewise, rapid-ON/OFF ramping stimuli also indicated that the functional deficit was localized to the ON pathway. Analysis of non-human primate retinal responses after drug application demonstrated a complexity to ON/OFF-pathway contributions to ramping ON/OFF ERG responses not previously anticipated. These results support the hypothesis that nyctalopin acts principally or exclusively within the ON pathway at the level of depolarizing bipolar cells, and thus human CSNB1-NYX subjects provide an opportunity to probe the primate visual system for consequences of ON- pathway deficits. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI USA. NIDCD, NIH, Bethesda, MD USA. RP Sieving, PA (reprint author), NEI, NIH, Bldg 31,Room 6A03,31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU NEI NIH HHS [EY-07003, R01-EY-06094] NR 103 TC 38 Z9 39 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2005 VL 93 IS 1 BP 481 EP 492 DI 10.1152/jn.00365.2004 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 880GV UT WOS:000225777900041 PM 15331616 ER PT J AU Croteau, D Walbridge, S Morrison, PF Butman, JA Vortmeyer, AO Johnson, D Oldfield, EH Lonser, RR AF Croteau, D Walbridge, S Morrison, PF Butman, JA Vortmeyer, AO Johnson, D Oldfield, EH Lonser, RR TI Real-time in vivo imaging of the convective distribution of a low-molecular-weight tracer SO JOURNAL OF NEUROSURGERY LA English DT Article DE central nervous system; computerized tomography; convection-enhanced delivery; drug delivery; Macaca mulatta ID ENHANCED DELIVERY; DRUG-DELIVERY; BRAIN-TUMORS; SPINAL-CORD; BLOOD-BRAIN; MACROMOLECULES; INFUSION; TISSUE; MICROINFUSION; DIFFUSION AB Object. Convection-enhanced delivery (CED) is increasingly used to distribute therapeutic agents to locations in the central nervous system. The optimal application of convective distribution of various agents requires the development of imaging tracers to monitor CED in vivo in real time. The authors examined the safety and utility of an iodine-based low-molecular-weight surrogate tracer for computerized tomography (CT) scanning during CED. Methods. Various volumes (total volume range 90-150 mul) of iopamidol (MW 777 D) were delivered to the cerebral white matter of four primates (Macaca mulatta) by using CED. The distribution of this imaging tracer was determined by in vivo real-time and postinfusion CT scanning (less than or equal to 5 days after infusion [one animal]) as well as by quantitative autoradiography (C-14-sucrose [all animals] and C-14-dextran [one animal]), and compared with a mathematical model. Clinical observation (less than or equal to 5 months) and histopathological analyses were used to evaluate the safety and toxicity of the tracer delivery. Real-time CT scanning of the tracer during infusion revealed a clearly definable region of perfusion. The volume of distribution (V-d) increased linearly (r(2) = 0.97) with an increasing volume of infusion (V-i). The overall V-d/V-i ratio was 4.1 +/- 0.7 (mean +/- standard deviation) and the distribution of infusate was homogeneous. Quantitative autoradiography confirmed the accuracy of the imaged distribution for a small (sucrose, MW 359 D) and a large (dextran, MW 70 kD) molecule. The distribution of the infusate was identifiable up to 72 hours after infusion. There was no clinical or histopathological evidence of toxicity in any animal. Conclusions. Real-time in vivo CT scanning of CED of iopamidol appears to be safe, feasible, and suitable for monitoring convective delivery of drugs with certain features and low infusion volumes. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Neuroradiol Sect, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 24 TC 38 Z9 39 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2005 VL 102 IS 1 BP 90 EP 97 DI 10.3171/jns.2005.102.1.0090 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 887FY UT WOS:000226292300014 PM 15658101 ER PT J AU Major, EO Ryschkewitsch, C Curfman, B Hou, J AF Major, Eugene O. Ryschkewitsch, Caroline Curfman, Blanche Hou, Jean TI JC virus and its association with cells of the immune system in the pathogenesis of progressive multifocal leukoencephalopathy (PML) SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Major, Eugene O.; Ryschkewitsch, Caroline; Curfman, Blanche; Hou, Jean] NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 19 EP 19 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200005 ER PT J AU Mannon, RB Bruno, D Cheng, OH Hale, D Kirk, AD Major, E AF Mannon, Roslyn B. Bruno, David Cheng, Orlena H. Hale, Douglas Kirk, Allan D. Major, Eugene TI The highs and lows of post-transplant immunosuppression: The role of BK polyoma viral monitoring SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Mannon, Roslyn B.; Cheng, Orlena H.; Hale, Douglas; Kirk, Allan D.] NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. [Bruno, David] Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. [Major, Eugene] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. RP Mannon, RB (reprint author), NIDDK, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 25 EP 25 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200010 ER PT J AU Monaco, MCG Maric, DA Grochow, RM Major, EO AF Monaco, Maria Chiara G. Maric, Dragan A. Grochow, Rebecca M. Major, Eugene O. TI JCV infection in primary human oligodendrocytes SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Monaco, Maria Chiara G.; Grochow, Rebecca M.; Major, Eugene O.] NINCDS, NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. [Maric, Dragan A.] NINCDS, NIH, Neurophysiol Lab, Bethesda, MD 20892 USA. RP Monaco, MCG (reprint author), NINCDS, NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 60 EP 60 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200043 ER PT J AU Ravichandran, V Sabath, BF Jensen, PN Major, EO AF Ravichandran, Veerasamy Sabath, Bruce F. Jensen, Peter N. Major, Eugene O. TI Modulation of binding between c-jun and nuclear factor-1 to JC virus promoter sequence: Implications for viral tropism SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Ravichandran, Veerasamy; Sabath, Bruce F.; Jensen, Peter N.; Major, Eugene O.] Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. [Ravichandran, Veerasamy; Sabath, Bruce F.; Jensen, Peter N.; Major, Eugene O.] NINDS, Bethesda, MD 20892 USA. [Ravichandran, Veerasamy; Sabath, Bruce F.; Jensen, Peter N.; Major, Eugene O.] NIH, Bethesda, MD 20892 USA. RP Ravichandran, V (reprint author), Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 68 EP 68 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200051 ER PT J AU Roth, BL AF Roth, Brian L. TI Regulation of serotonin receptor expression: Relevance for the pharmacotheraphy of PML SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Roth, Brian L.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. [Roth, Brian L.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. [Roth, Brian L.] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. [Roth, Brian L.] Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Cleveland, OH 44106 USA. [Roth, Brian L.] Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Prgm, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 79 EP 79 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200060 ER PT J AU Kowalski, RJ Mannon, R Kirk, A Jonsson, J Post, DR Britz, J AF Kowalski, Richard J. Mannon, Rosyln Kirk, Allan Jonsson, Johann Post, Diane R. Britz, Judith TI Immune function monitoring with the Cylex ImmuKnow, assay to preemptively identify patients at greater risk for human polyomavirus infection SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Kowalski, Richard J.; Post, Diane R.; Britz, Judith] Cylex Inc, Fairfax, VA USA. [Mannon, Rosyln; Kirk, Allan] NIDDK, NIH, DHHS, Fairfax, VA USA. [Jonsson, Johann] INOVA Hosp, Fairfax, VA USA. RP Kowalski, RJ (reprint author), Cylex Inc, Fairfax, VA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 98 EP 98 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200076 ER PT J AU Nath, A Vanketaramana, A Reich, DS Major, EO AF Nath, Avindra Vanketaramana, Anita Reich, Daniel S. Major, Eugene O. TI Progression of PML despite treatment with beta-interferon in a patient with HIV infection SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Nath, Avindra; Vanketaramana, Anita; Reich, Daniel S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Major, Eugene O.] NINDS, NIH, Bethesda, MD 20892 USA. RP Nath, A (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 112 EP 112 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200086 ER PT J AU Joseph, J Kopnisky, KL Nunn, M AF Joseph, J Kopnisky, KL Nunn, M TI NeuroAIDS research in resource-limited countries. Emerging priorities of the US National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Joseph, J (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 11 SU 1 BP 1 EP 3 DI 10.1080/13550280590922658 PG 3 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 929VM UT WOS:000229374700001 PM 15960233 ER PT J AU Joseph, J Prasad, V AF Joseph, J Prasad, V TI NeuroAIDS in the developing world SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. Albert Einstein Coll Med, AIDS Int Training & Res Program, Bronx, NY 10467 USA. RP Joseph, J (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 11 SU 1 BP 4 EP 6 DI 10.1080/13550280590922702 PG 3 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 929VM UT WOS:000229374700002 PM 15960234 ER PT J AU Jenkins, J Grady, PA Collins, FS AF Jenkins, J Grady, PA Collins, FS TI Nurses and the genomic revolution SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE nursing; genetics; trends; genomics ID MALIGNANCIES; MEDICINE AB Purpose: To increase nurses' genetics and genomics literacy through a series of articles focused on genomic research discoveries and their importance for nursing education, practice, policy, and research. Organizing Framework: "Genomics for Health" is one of three themes, along with genomes to biology and genomes to society, emanating from applications of the Human Genome Project (HGP). Methods: In this series of articles, nurse scientists who are experts in genetics and genomics sciences explain terminology, provide background information about the HGP, discuss clinical examples, and recommend changes in nursing practice, education, and research. Conclusions: The HGP has already led to major changes in clinical practice, research, education, and policy, and even more dramatic changes are predicted for people throughout the world. Mastering this information is necessary for nurses globally because genomic information will ultimately pervade all of health care. 2005 Sigma Theta Tau International. C1 NHGRI, NIH, Bethesda, MD 20892 USA. NINR, NIH, Bethesda, MD 20892 USA. RP Jenkins, J (reprint author), NHGRI, NIH, 31 Ctr Dr,Bldg 31,Room 4B09, Bethesda, MD 20892 USA. EM jean.jenkins@nih.gov NR 15 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2005 VL 37 IS 2 BP 98 EP 101 DI 10.1111/j.1547-5069.2005.00020.x PG 4 WC Nursing SC Nursing GA 925ES UT WOS:000229034900004 PM 15960052 ER PT J AU Feetham, S Thomson, EJ Hinshaw, AS AF Feetham, S Thomson, EJ Hinshaw, AS TI Nursing leadership in genomics for health and society SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE genomics; genetics; health; nursing; leadership; research; education; practice ID FAMILY-HISTORY; PRIMARY-CARE; BRCA2 MUTATIONS; KIN-COHORT; GENETICS; DISEASE; GENOTYPE; MEDICINE; HEMOCHROMATOSIS; PENETRANCE AB Purpose: This article is part of the series regarding genomics and nursing practice, science, education, and policy. Issues in genetic testing, genetic information and the lessons learned through applications of genetic and genomic science are analyzed and discussed. Framework: Scientists, scholars, and members of the public have articulated a vision to guide genomics research and scholarship. The three overarching themes of this conceptual framework are genomes to biology, genomes to health, and genomes to society. Conclusions: Nurses can promote the use of genomic research technologies and information in the context of health, biology, and society, as well as in nursing research, practice, education, and policy. (c) 2005 Sigma Theta Tau International. C1 US Hlth Resources & Serv Adm, Ctr Qual, Dept Hlth & Human Serv, Rockville, MD 20857 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RP Feetham, S (reprint author), US Hlth Resources & Serv Adm, Ctr Qual, Dept Hlth & Human Serv, 17 C 26 Parklawn Bldg,5600 Fishers Lane, Rockville, MD 20857 USA. EM sfeetham@hrsa.gov NR 71 TC 22 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2005 VL 37 IS 2 BP 102 EP 110 DI 10.1111/j.1547-5069.2005.00021.x PG 9 WC Nursing SC Nursing GA 925ES UT WOS:000229034900005 PM 15960053 ER PT J AU O'Connor, DL Latulippe, ME Campos, C Merlos, C Villalpando, S Picciano, MF AF O'Connor, DL Latulippe, ME Campos, C Merlos, C Villalpando, S Picciano, MF TI Folate deficiency does not alter the usefulness of the serum transferrin receptor concentration as an index for the detection of iron deficiency in Mexican women during early lactation SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2000 Meeting CY APR 14-19, 2000 CL SAN DIEGO, CA DE iron; folate; lactation; transferrin receptor ID PREGNANT-WOMEN; FERRITIN; DIAGNOSIS; VITAMIN-B-12; PERFORMANCE; INFANTS; ANEMIA; RATIO; MEN AB The purpose of this study was to investigate the usefulness of soluble serum transferrin receptor (TfR) concentration, TfR index and log TfR:ferritin ratio (TfR outcomes) in detecting tissue Fe deficiency among breast-feeding Otomi women residing in Capulhuac, Mexico (2800 m above sea level) and to determine whether folate deficiency modifies the interpretation of these data. Lactating women (n = 68) provided blood samples at 22 +/- 13 d (mean +/- SD) postpartum. Using the 3-index Fe assessment model with and without Hb, 2 women (3%) had Fe-deficient erythropoiesis, 24 (36%) Fe deficiency anemia, and 19 (29%) indeterminate Fe status; 29 (43%) and 5 (7.5%) women had plasma and erythrocyte folate concentrations below normative cutoff values, respectively. Mean values for TfR outcomes were higher among women classified as Fe deficient than those who were Fe sufficient, but did not differ with low or normal blood folate concentrations. Similarly, TfR outcomes did not differ among women with normocytic or macrocytic erythrocytes. Receiver-operating characteristic (ROC) curves generated for TfR outcomes yielded areas under the curve from 0.62 to 0.68, indicating that each of these measures, on. its own, is a poor predictor of tissue Fe deficiency in lactating women. In conclusion, low blood folate concentrations or the presence of macrocytosis in Otomi women from Capulhuac, Mexico (moderate altitude) did not influence the utility of TfR outcomes for the detection of Fe deficiency during early lactation. Further, on their own, TfR, TfR index, and TfR:ferritin ratio were poor predictors of tissue Fe deficiency for any given individual. C1 Univ Toronto, Dept Nutrit Sci, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP O'Connor, DL (reprint author), Univ Toronto, Dept Nutrit Sci, Toronto, ON M5G 1X8, Canada. EM deborah_l.o'connor@sickkids.ca OI Villalpando, Salvador/0000-0001-6429-3816 NR 44 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2005 VL 135 IS 1 BP 144 EP 149 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 886ZX UT WOS:000226273000024 PM 15623846 ER PT J AU Charmandari, E Chrousos, GP Merke, DP AF Charmandari, E Chrousos, GP Merke, DP TI Adrenocorticotropin hypersecretion and pituitary microadenoma following bilateral adrenalectomy in a patient with classic 21-hydroxylase deficiency SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE congenital adrenal hyperplasia; 21-hydroxylase deficiency; adrenalectomy; adrenal rest tissue; pituitary microadenoma ID STIMULATION TEST; HYPERPLASIA; DISEASE; TUMOR; AID AB Bilateral adrenalectomy is an acceptable alternative treatment in salt-wasting 21-hydroxylase deficiency when conventional steroid replacement therapy fails to control hyperandrogenism. Objections to surgical adrenalectomy have been based on surgical risk, possible loss of protective adrenal function, and the risk of ACTH-induced activation of adrenal rest tissue. We report a young female with salt-wasting CAH, who underwent bilateral adrenalectomy and developed severe hyperpigmentation, progressively marked corticotropin hypersecretion to concentrations seen in Nelson's syndrome (5,000-7,000 pg/ml), a pituitary microadenoma 5 years postoperatively, and probable ectopic adrenal rest tissue. Corticotropin concentrations failed to respond to ovine corticotropin-releasing hormone (oCRH) (1 mug/kg given as an i.v. bolus), but did suppress following both hydrocortisone administration (100 mg given as an i.v. bolus) and a low dose (0.5 mg given orally every 6 h for 48 h) dexamethasone suppression test. Patients with CAH have hyperactivity of the hypothalamic-pituitary-adrenal axis and are at risk for pituitary tumor formation. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NICHHD, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD USA. RP Charmandari, E (reprint author), Great Ormond St Hosp Children, Dept Endocrinol, 9th Floor, Southwood Bldg,Great Ormond St, London WC1N 3JH, England. EM charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 14 TC 10 Z9 12 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JAN PY 2005 VL 18 IS 1 BP 97 EP 101 PG 5 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 890TY UT WOS:000226534900011 PM 15679075 ER PT J AU Rowland, JH AF Rowland, JH TI Foreword: Looking beyond cure: Pediatric cancer as a model SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Editorial Material ID COMMUNICATION; SURVIVORS C1 NCI, Off Canc Survivorship, Dept Hlth & Human Serv, NIH, Washington, DC USA. RP Rowland, JH (reprint author), NCI, Off Canc Survivorship, Dept Hlth & Human Serv, NIH, Washington, DC USA. EM rowlandj@mail.nih.gov NR 9 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JAN-FEB PY 2005 VL 30 IS 1 BP 1 EP 3 DI 10.1093/jpepsy/jsi010 PG 3 WC Psychology, Developmental SC Psychology GA 884OL UT WOS:000226094800001 PM 15610979 ER PT J AU Meyer, EA Fuemmeler, BF AF Meyer, EA Fuemmeler, BF TI Commentary: Psychosocial functioning of children and adolescents surviving cancer: The junior investigators' perspective SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02445 USA. Childrens Hosp, Boston, MA USA. NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. RP Meyer, EA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Room D312, Boston, MA 02445 USA. EM tony_meyer@dfci.harvard.edu NR 4 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD JAN-FEB PY 2005 VL 30 IS 1 BP 47 EP 49 DI 10.1093/jpepsy.jsi015 PG 3 WC Psychology, Developmental SC Psychology GA 884OL UT WOS:000226094800006 PM 15610984 ER PT J AU Richani, K Romero, R Soto, E Espinoza, J Nien, JK Chaiworapongsa, T Refuerzo, J Blackwell, S Edwin, SS Santolaya-Forgas, J Mazor, M AF Richani, K Romero, R Soto, E Espinoza, J Nien, JK Chaiworapongsa, T Refuerzo, J Blackwell, S Edwin, SS Santolaya-Forgas, J Mazor, M TI Unexplained intrauterine fetal death is accompanied by activation of complement SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE pregnancy; intrauterine fetal death; anaphylatoxins; complement system; C3a; C4a; C5a; preeclampsia ID DECAY-ACCELERATING FACTOR; HUMAN C5A ANAPHYLATOXIN; TUMOR-NECROSIS-FACTOR; HUMAN-PREGNANCY; REGULATORY PROTEINS; RESPIRATORY BURST; ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; HUMAN EOSINOPHILS; HUMAN TROPHOBLAST AB Objective: Activation of the complement system has recently been implicated in the mechanisms of fetal loss in the antiphospholipid syndrome. It is, however, possible that complement activation is also involved in other causes of fetal death in the second and third trimesters of pregnancy. We therefore conducted a study to determine whether fetal death is associated with changes in the maternal plasma concentrations of complement split products or anaphylatoxins (C3a, C4a, and C5a). Study design: A cross-sectional study was designed to include normal pregnant women (n=60) and patients with fetal death (n=60). Patients with fetal death were classified according to the cause of fetal demise into: a) unexplained (n=44); b) associated with preeclampsia, (n=8); and c) associated with chromosomal abnormalities or major congenital fetal anomalies (n = 8). The plasma concentrations of C3a, C4a. and C5a were measured using sensitive and specific ELISAs. Non-parametric statistics were used for analysis. A P value of <0.05 was considered significant. Results: 1) The median plasma concentration of C5a was higher in patients with fetal death than in normal pregnant women [median 16 ng/mL (range 4.5-402.5) vs. median 11.6 ng/mL (range 1.2-87.1), respectively; P<0.001]; 2) patients with an unexplained fetal death and those associated with preeclampsia. had a higher median plasma C5a. concentration than normal pregnant women (P=0.002 and P<0.001, respectively); 3) no differences were., observed in the, maternal plasma concentrations of C3a and C4a. among the study groups. Conclusions: Unexplained fetal death is associated with evidence of complement activation. C1 Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Detroit, MI USA. Ben Gurion Univ Negev, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 101 TC 19 Z9 21 U1 0 U2 2 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2005 VL 33 IS 4 BP 296 EP 305 DI 10.1515/JPM.2005.052 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 950YC UT WOS:000230893700004 PM 16207114 ER PT J AU Soto, E Romero, R Richani, K Espinoza, J Nien, JK Chaiworapongsa, T Santolaya-Forgas, J Edwin, SS Mazor, M AF Soto, E Romero, R Richani, K Espinoza, J Nien, JK Chaiworapongsa, T Santolaya-Forgas, J Edwin, SS Mazor, M TI Anaphylatoxins in preterm and term labor SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE parturition; human labor; preterm labor; intra-amniotic infection; anaphylatoxin; C3a; C4a; C5a ID TUMOR-NECROSIS-FACTOR; COMPLEMENT-SYSTEM; HUMAN-NEUTROPHILS; RESPIRATORY BURST; ENDOTHELIAL-CELLS; HUMAN EOSINOPHILS; PREMATURE LABOR; C5A; C3A; ACTIVATION AB Objective: The complement system plays a central role in the first line of defense against invading pathogens, and its activation involves the release of potent proinflammatory mediators such as anaphylatoxins C3a, C4a and C5a. The aim of this study was to determine whether differences existed in maternal plasma anaphylatoxin concentrations between patients with term and preterm parturition. Study design: A cross-sectional study was designed to determine the plasma anaphylatoxin concentrations in 296 pregnant women in the following groups: 1) normal pregnancy between 20-36 6/7 weeks (n = 64); 2) term not in labor (n = 70); 3) term in labor (n = 60); and 4) preterm labor with intact membranes (n = 102). Women with preterm labor were classified into: a) term delivery (n=24); b) preterm delivery without intra-amniotic infection (IAl) (n = 62); and c) pretemn delivery with IAI (n = 16). Concentrations of C3a, C4a and C5a were determined by ELISAs. Statistical analysis was conducted with non-parametric methods. Results: 1) The median plasma C5a concentration was lower in women at term in labor than in those not in labor (P < 0.001). In contrast, there were no differences in plasma C3a and C4a concentrations between the two groups (P>0.05). 2) Among patients with pretemn labor, those with IAI had a higher median plasma C5a concentration than those without IAI and those who delivered at term (post-hoc tests P<0.001 and P=0.01, respectively). When comparing the preterm labor subgroups with normal pregnancy, only women with preterm delivery and IAI had a median plasma C5a concentration higher than that of normal pregnant women (Kruskal-Wallis P<0.001, post hoc test P < 0.001). There was no difference in the plasma C4a concentration among patients with preterm labor. The median plasma C3a concentration in patients with preterm labor with IAI was higher than in those without IAI (Kruskal-Wallis P=0.01, and post-hoc test P=0.005). There was no difference in the plasma C3a concentrations between women with preterm labor who delivered at term and those with preterm delivery, with or without IAI. In addition, no differences were observed in the median plasma C3a concentration between women with normal pregnancy and those in each of the preterm labor subgroups. Conclusions: The maternal plasma concentration of anaphylatoxin C5a is increased in women with preterm labor and IAI, but not in spontaneous labor at term. C1 Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Detroit, MI USA. Ben Gurion Univ Negev, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU NICHD NIH HHS [Z01 HD002400-14] NR 60 TC 23 Z9 24 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2005 VL 33 IS 4 BP 306 EP 313 DI 10.1515/JPM.2005.051 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 950YC UT WOS:000230893700005 PM 16207115 ER PT J AU Olariu, A Yamada, K Nabeshima, T AF Olariu, A Yamada, K Nabeshima, T TI Amyloid pathology and protein kinase C (PKQ): Possible therapeutics effects of PKC activators SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article DE amyloid protein; Alzheimer's disease; signal transduction; protein kinase C; cell death ID ALZHEIMERS-DISEASE PATIENTS; PRECURSOR PROTEIN; DOWN-REGULATION; HUMAN BRAIN; IN-VIVO; A-BETA; ALPHA; EXPRESSION; ISOFORMS; MODELS AB Amyloid beta-protein (Abeta) is one of the most studied peptides in human neurodegenerative disorders. Although much has been learned about the biochemistry of this peptide, fundamental questions such as when and how the Abeta becomes pathologic remain unanswered. In this article we review the recent findings on the biology and pathology of Abeta and the role protein kinase C (PKC) plays in these processes. The potential neuroprotective role of PKC and the possible therapeutic effects of PKC activators in Alzheimer's disease (AD) will be discussed. Briefly, comments will be also addressed on the role of PKC in cell death and neurogenesis in AD. C1 NIMH, Unit Neuroplastic, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Grad Sch Nat Sci & Technol, Div Life Sci, Neuropharmacol Lab, Kanazawa, Ishikawa 9201192, Japan. Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Nagoya, Aichi 4668560, Japan. RP Olariu, A (reprint author), NIMH, Unit Neuroplastic, NIH, Bethesda, MD 20892 USA. EM anaolariu@mail.nih.gov RI Yamada, Kiyofumi/I-7487-2014 OI Yamada, Kiyofumi/0000-0002-5280-5180 NR 31 TC 14 Z9 14 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD JAN PY 2005 VL 97 IS 1 BP 1 EP 5 DI 10.1254/jphs.CPJ04004X PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892FI UT WOS:000226635000001 PM 15655301 ER PT J AU Lakatta, EG AF Lakatta, EG TI Arterial aging in apparent health promotes arterial diseases SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 2P EP 2P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100003 ER PT J AU Mamiya, T Sora, I Uhl, G Ukai, M AF Mamiya, T Sora, I Uhl, G Ukai, M TI Role of endomorphin-1 on the process of learning and memory in the water-finding test in mice. SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Meijo Univ, Fac Pharm, Dept Chem Pharmacol, Tempaku Ku, Nagoya, Aichi 4688503, Japan. Tohoku Univ, Grad Sch Med, Div Psychobiol, Aoba Ku, Sendai, Miyagi 9808574, Japan. Tokyo Inst Psychiat, Dept Mol Psychiat, Setagaya Ku, Tokyo 1568585, Japan. NIDA, IRP, NIH, USA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 60P EP 60P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100169 ER PT J AU Tajima, O Tsutiya, K Ohnishi, H Kanematsu, Y Yoshizumi, M Tamaki, T Mason, R Takiguti, Y AF Tajima, O Tsutiya, K Ohnishi, H Kanematsu, Y Yoshizumi, M Tamaki, T Mason, R Takiguti, Y TI Detection of protein-derived radicals by immunochemical technique SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Univ Tokushima, Inst Hlth Biosci, Dept Clin Pharmacol, Tokushima 7708505, Japan. Univ Tokushima, Inst Hlth Biosci, Dept Pharmacol, Tokushima 7708503, Japan. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 62P EP 62P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100177 ER PT J AU Unno, T Sakamoto, T Uchiyama, M Matsuyama, H Yamada, M Wess, J Komori, S AF Unno, T Sakamoto, T Uchiyama, M Matsuyama, H Yamada, M Wess, J Komori, S TI Role of M-2 and M-3 receptor subtypes in the activation of muscarinic receptor-operated cationic channels in mouse intestinal smooth muscle cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RIKEN, Brain Sci Inst, Saitama 3510198, Japan. Gifu Univ, Dept Vet Pharmacol, Gifu 5011193, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 75P EP 75P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100220 ER PT J AU Tajima, S Tsutiya, K Ohnishi, H Kanematsu, Y Yoshizumi, M Tamaki, T Mason, R Takiguti, Y AF Tajima, S Tsutiya, K Ohnishi, H Kanematsu, Y Yoshizumi, M Tamaki, T Mason, R Takiguti, Y TI Detection of protein-derived radicals by immunochemical technique SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Univ Tokushima, Inst Hlth Biosci, Dept Clin Pharmacol, Tokushima 7708505, Japan. Univ Tokushima, Inst Hlth Biosci, Dept Pharmacol, Tokushima 7708503, Japan. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 88P EP 88P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100271 ER PT J AU Eustace, BK Sakurai, T Stewart, JK Yimlamai, D Unger, C Zehetmeier, C Lain, B Torella, C Henning, SW Beste, G Scroggins, BT Neckers, L Ilag, LL Jay, DG AF Eustace, BK Sakurai, T Stewart, JK Yimlamai, D Unger, C Zehetmeier, C Lain, B Torella, C Henning, SW Beste, G Scroggins, BT Neckers, L Ilag, LL Jay, DG TI Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. RIKEN, BSI, Lab Struct Neuropathol, Wako, Saitama 35101, Japan. Xerion Parm, Martinsried, Germany. NCI, Cell Canc Biol Br, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 90P EP 90P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100281 ER PT J AU Mamiya, T Sora, I Uhl, G Ukai, M AF Mamiya, T Sora, I Uhl, G Ukai, M TI Role of endomorphin-1 on the process of learning and memory in the water-finding test in mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Meijo Univ, Fac Pharm, Dept Chem Pharmacol, Tempaku Ku, Nagoya, Aichi 4688503, Japan. Tohoku Univ, Grad Sch Med, Div Psychobiol, Aoba Ku, Sendai, Miyagi 9808574, Japan. Tokyo Inst Psychiat, Dept Mol Psychiat, Setagaya Ku, Tokyo 1568585, Japan. NIDA, IRP, NIH, USA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 101P EP 101P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100323 ER PT J AU Koshimizu, T Mu-Lan, H Ueno, S Tanoue, A Yanagihara, N Stojilkovic, S Tsujimoto, G AF Koshimizu, T Mu-Lan, H Ueno, S Tanoue, A Yanagihara, N Stojilkovic, S Tsujimoto, G TI C-terminal splicing enhances physical interactions of cytoplasmic carboxy-termini of P2X receptors SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Genom Drug Disc Sci, Kyoto 6068501, Japan. NICHD, ERRB, NIH, Bethesda, MD 20892 USA. Univ Occupat & Environm Hlth, Jap Sch Med, Dept Pharmacol, Fukuoka 8078555, Japan. Nat Res Inst Child Hlth Dev, Dept Mol Cell Pharmacol, Tokyo 1542567, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 145P EP 145P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886100492 ER PT J AU Hikiba, H Watanabe, E Barrett, JC Tsutsui, T AF Hikiba, H Watanabe, E Barrett, JC Tsutsui, T TI Ability of fourteen chemical agents used in dental practice to induce chromosome aberrations in Syrian hamster embryo cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article DE chromosome aberration; chemical agents used in dentistry; Syrian hamster embryo cell ID UNSCHEDULED DNA-SYNTHESIS; TRANSFORMATION; EUGENOL; DIETHYLSTILBESTROL; MUTAGENICITY; GENOTOXICITY; FORMALDEHYDE; TOXICITY; PHENOL; ASSAYS AB To assess the genotoxicity of 14 chemical agents used in dental practice, the ability of these agents to induce chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Statistically significant increases in the frequencies of chromosome aberrations were induced in SHE cells treated with 7 of 10 chemical agents used as endodontic medicaments, that is, carbol camphor, m-cresol, eugenol, guaiacol, zinc oxide, hydrogen peroxide, and formaldehyde. The other 3 chemical agents, that is, thymol, glutaraldehyde, and iodoform, did not increase the levels of chromosome aberrations. Of the 4 chemical agents that are used as an antiseptic on the oral mucosa, chromosome aberrations were induced by iodine, but not by the other 3 antiseptics, benzalkonium chloride, benzethonium chloride, and chlorhexidine. Among the 6 chemical agents exhibiting a negative response in the assay, only thymol induced chromosome aberrations in the presence of exogenous metabolic activation. Our results indicate that chemical agents having a positive response in the present study are potentially genotoxic to mammalian cells and need to be studied further in detail. C1 Nippon Dent Univ Tokyo, Sch Dent, Dept Pharmacol, Chiyoda Ku, Tokyo 1028159, Japan. NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Tsutsui, T (reprint author), Nippon Dent Univ Tokyo, Sch Dent, Dept Pharmacol, Chiyoda Ku, 1-9-20 Fujimi, Tokyo 1028159, Japan. EM takeki@tokyo.ndu.ac.jp NR 28 TC 36 Z9 38 U1 2 U2 10 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD JAN PY 2005 VL 97 IS 1 BP 146 EP 152 DI 10.1254/jphs.FPJ04044X PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 892FI UT WOS:000226635000022 PM 15665446 ER PT J AU Ide, S Minami, M Uhl, GR Ishihara, K Sora, I Ikeda, K AF Ide, S Minami, M Uhl, GR Ishihara, K Sora, I Ikeda, K TI The analyses of the antinociceptive and rewarding effects of buprenorphine and tramadol in mu-opioid receptor knockout mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Hiroshima Int Univ, Dept Pharmaceut Sci, Neuropharmacol Lab, Hiroshima 7370112, Japan. Tokyo Inst Psychiat, Dept Mol Psychiat, Tokyo 1568585, Japan. Kyoto Univ, Fac Pharmaceut Sci, Dept Mol Pharmacol, Kyoto 6068501, Japan. MNB, NIDA, IRP, Baltimore, MD 21224 USA. Tohoku Univ, Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 9808574, Japan. RI Ide, Soichiro/D-5472-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 203P EP 203P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886101217 ER PT J AU Niwa, M Nitta, A Yamada, Y Saito, K Seishima, M Liya, S Noda, Y Nabeshima, T AF Niwa, M Nitta, A Yamada, Y Saito, K Seishima, M Liya, S Noda, Y Nabeshima, T TI A possibility of Leu-Ile as a novel therapeutic agent for methamphetamine-induced dependence SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 78th Annual Meeting of the Japanese-Pharnacological-Society CY MAR 22-24, 2005 CL Yokohama, JAPAN SP Japanese Pharmacol Soc C1 Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Nagoya, Aichi 4668360, Japan. Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2005 VL 97 SU 1 BP 270P EP 270P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 909UL UT WOS:000227886101488 ER PT J AU Crosby, MB Svenson, JL Zhang, J Nicol, CJ Gonzalez, FJ Gilkeson, GS AF Crosby, MB Svenson, JL Zhang, J Nicol, CJ Gonzalez, FJ Gilkeson, GS TI Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPAR gamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NF-KAPPA-B; RECEPTOR-GAMMA; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); MACROPHAGE ACTIVATION; IN-VITRO; INFLAMMATORY CYTOKINES; INDUCED ARTHRITIS; IFN-GAMMA; LIGANDS; GENE AB Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 muM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN) gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 muM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 muM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFN gamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 muM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 muM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation. C1 Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. NCI, Met Lab, NIH, Bethesda, MD USA. Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathon Lucas St,Suite 912,POB 25063, Charleston, SC 29425 USA. EM gilkeson@musc.edu FU NIAMS NIH HHS [AR45476, AR47451] NR 40 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2005 VL 312 IS 1 BP 69 EP 76 DI 10.1124/jpet.104.074005 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 880CM UT WOS:000225766400009 PM 15356214 ER PT J AU Fishel, ML Newell, DR Griffin, RJ Davison, R Wang, LZ Curtin, NJ Zuhowski, EG Kasza, K Egorin, MJ Moschel, RC Dolan, ME AF Fishel, ML Newell, DR Griffin, RJ Davison, R Wang, LZ Curtin, NJ Zuhowski, EG Kasza, K Egorin, MJ Moschel, RC Dolan, ME TI Effect of cell cycle inhibition on cisplatin-induced cytotoxicity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DEPENDENT KINASE INHIBITORS; HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; PHASE-I TRIAL; HISTONE DEACETYLASE; CANCER; CDK2; EXPRESSION; PURINE; O-6-BENZYLGUANINE; OVEREXPRESSION AB Pharmacological inhibitors of cyclin-dependent kinase (CDK) 2 are currently in preclinical and clinical development. The purpose of our work was to evaluate a series of guanine derivatives for their ability to inhibit CDK2, affect cell cycle progression, and enhance the cytotoxic and apoptotic effects of cisplatin. A panel of guanine derivatives, including O-6-benzylguanine (O-6-BG), S-6-benzyl-6-thioguanine (S-6-BG), S-6-[(cyclohexyl)methyl]-6-thioguanine (S-6-CMG), O-6-[(cyclohexyl) methyl] guanine (O-6-CMG), O-6-benzyl-9-methylguanine (9-CH3-BG), O-6-[(cyclohexyl)methyl]-9-methylguanine (9-CH3-CMG), and 7-benzylguanine (N7-BG), exhibited varying degrees of CDK2 inhibition with O-6-CMG being the most potent and 9-CH3-BG, 9-CH3-CMG, and N7-BG the least potent compounds. Treatment with S-6-CMG and O-6-CMG significantly decreased the percentage of cells in S phase. In SQ20b and SCC61 head and neck cancer cell lines, the most potent CDK2 inhibitor, O-6-CMG, was also the most effective at enhancing cisplatin-induced cytotoxicity and apoptosis. Cisplatin-induced DNA platination increased in SQ20b cells pretreated with S-6-BG, S-6-CMG, and O-6-CMG. Treatment with both O-6-BG and trichostatin A, an indirect cell cycle inhibitor, demonstrated additive effects on cisplatin-induced cytotoxicity. In summary, we have identified a group of guanine derivatives that were effective modulators of cisplatin-induced cytotoxicity and apoptosis. C1 Univ Chicago, Dept Med, Committee Canc Biol, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Univ Newcastle, No Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England. Univ Pittsburgh, Pittsburgh Canc Inst, Pittsburgh, PA USA. Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD USA. RP Dolan, ME (reprint author), Univ Chicago, Dept Med, Committee Canc Biol, 5841 S Maryland Ave,Box MC2115, Chicago, IL 60637 USA. EM edolan@medicine.bsd.uchicago.edu FU NCI NIH HHS [CA81485] NR 42 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2005 VL 312 IS 1 BP 206 EP 213 DI 10.1124/jpet.104.073924 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 880CM UT WOS:000225766400025 PM 15304523 ER PT J AU Vaupel, DB Tella, SR Huso, DL Wagner, VO Mukhin, AG Chefer, SI Horti, AG London, ED Koren, AO Kimes, AS AF Vaupel, DB Tella, SR Huso, DL Wagner, VO Mukhin, AG Chefer, SI Horti, AG London, ED Koren, AO Kimes, AS TI Pharmacological and toxicological evaluation of 2-fluoro-3(2(S)-azetidinylmethoxy)pyridine (2-F-A-85380), a ligand for imaging cerebral nicotinic acetylcholine receptors with positron emission tomography SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MONKEYS MACACA-MULATTA; IN-VIVO; RADIATION-DOSIMETRY; BLOOD-PRESSURE; RADIOLIGAND; RESPONSES; AFFINITY; DOGS; RAT; 5-I-A-85380 AB 2-[F-18] fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-[F-18] F-A-85380), a positron emission tomography (PET) radioligand for neuronal alpha4beta2* nicotinic acetylcholine receptors, was evaluated for its pharmacology and safety. In the Ames test for mutagenicity, 2-F-A-85380 was without effect in five bacterial strains. No evidence of gross pathology or histopathological changes occurred in either 2- day acute (0.4 4000 nmol/kg i.v.) or 14-day expanded acute ( 40 - 4000 nmol/kg i. v.) toxicity studies in mice. Similarly, hematology and serum chemistry values in rhesus monkeys administered 60 nmol/kg i. v. were not affected over 14 days. Like nicotine, 2- F-A-85380 produced convulsions in mice at very high doses. The ED50 value of 2-F-A-85380 for eliciting tonic-clonic convulsions (5.0 mumol/kg i. v.) was nearly 4 times greater than that of nicotine (ED50 = 1.4 mumol/kg i. v.). Lower doses of 2-F-A-85380 ( 30 - 300 nmol/kg i.v.) and nicotine ( 20 - 400 nmol/kg i.v.) increased systolic and diastolic blood pressure, heart rate, and cardiac contractility in rats. Notably, the PR, QRS, or QTc intervals of the rat electrocardiogram were unaffected by either drug. Dosimetry studies indicated that the urinary bladder wall was the critical organ and total radiation exposure was within acceptable limits. Estimated doses of 2-F-A-85380 required to elevate blood pressure and heart rate by 10% ranged from 40 to 58 nmol/ kg i.v. Nevertheless, the estimated radiopharmaceutically relevant dose of [F-18] 2-F-A-8380 required for initial PET imaging studies, 10 pmol/kg, is less than 1/4000th of the doses calculated ( 40 - 58 nmol/ kg i.v.) to elevate blood pressure and heart rate by 10% in humans and should elicit no clinically significant effects and have acceptable dosimetry. C1 NIDA, Neuroimaging Res Branch, Intramural Res Program, US Dept HHS, Baltimore, MD USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD USA. BioReliance Inc, Rockville, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA USA. RP Vaupel, DB (reprint author), NIDA IRP, Neuroimaging Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bvaupel@intra.nida.nih.gov FU NCI NIH HHS [CA062924]; NCRR NIH HHS [RR000171] NR 39 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2005 VL 312 IS 1 BP 355 EP 365 DI 10.1124/jpet.104.073999 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 880CM UT WOS:000225766400044 PM 15331657 ER PT J AU Fisahn, A Heinemann, SF McBain, CJ AF Fisahn, A Heinemann, SF McBain, CJ TI The kainate receptor subunit GluR6 mediates metabotropic regulation of the slow and medium AHP currents in mouse hippocampal neurones SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID ACTIVATED POTASSIUM CURRENTS; CA1 PYRAMIDAL NEURONS; AFTER-HYPERPOLARIZATION; EPILEPTIFORM ACTIVITY; GAMMA OSCILLATIONS; GUINEA-PIG; K+ CURRENT; EXCITABILITY; CHANNELS; SEIZURES AB Kainate receptors (KARs) play an important role in synaptic physiology, plasticity and pathological phenomena such as epilepsy. However, the physiological implications for single cells and neuronal networks of the distinct expression patterns of KAR subunits are unknown. One intriguing effect of KAR activation is a long-term change to intrinsic neuronal 0 13 excitability and neuronal firing patterns, such as single-spike and spike-burst firing. In this study, study, we describe the role of kainate receptor subunits in the metabotropic regula on of the slow and medium afterhyperpolarization (AHP) currents (I-sAHP, I-mAHP). Using whole-cell patch-clamp recordings from CA3 pyramidal cells of wild-type (WT) and KAR knockout mice, we show that the kainate-induced decrease of I-sAHP and I-mAHP amplitude is protein-kinase-C-dependent and absent in GluR6(-/-) but not GluR5(-/-) pyramidal neurones. Our findings suggest that activation of GluR6-containing KARs modulates AHP amplitude, and influences the firing frequency of pyramidal neurones. C1 Karolinska Inst, Dept Neurosci, Nobel Inst Neurophysiol, SE-17177 Stockholm, Sweden. NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 93037 USA. RP Fisahn, A (reprint author), Karolinska Inst, Dept Neurosci, Nobel Inst Neurophysiol, Retzius Vag 8 A3-5, SE-17177 Stockholm, Sweden. EM andre.fisahn@neuro.ki.se FU NINDS NIH HHS [R01 NS028709, NS28709] NR 25 TC 51 Z9 54 U1 1 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2005 VL 562 IS 1 BP 199 EP 203 DI 10.1113/j.physiol.2004.077412 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 891OO UT WOS:000226590600020 PM 15539395 ER PT J AU Ronesi, J Lovinger, DM AF Ronesi, J Lovinger, DM TI Induction of striatal long-term synaptic depression by moderate frequency activation of cortical afferents in rat SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID DOPAMINE D2 RECEPTORS; NUCLEUS-ACCUMBENS; DORSAL STRIATUM; CORTICOSTRIATAL SYNAPSES; NEUROTRANSMITTER RELEASE; ENDOCANNABINOID RELEASE; ENDOGENOUS CANNABINOIDS; IN-VITRO; PLASTICITY; NEURONS AB The striatum regulates motor output, and it is thought that changes in the synaptic efficacy of inputs to the striatum contribute to motor learning and habit formation. Previously several laboratories have observed that brief high frequency stimulation (HFS) of cortical afferents innervating the dorsolateral striatum induces a long-term decrease in synaptic efficacy called long-term depression (LTD). We recently showed that HFS-induced striatal LTD requires retrograde signalling involving postsynaptic release of endocannabinoids and activation of presynaptic CB1 cannabinoid receptors. In the present study we have employed whole-cell recording in brain slices to examine a new form of LTD at corticostriatal synapses that can be induced by a 10 Hz, 5 min train. The decrease in synaptic efficacy is associated with a decrease in presynaptic release probability, as demonstrated by a decrease in frequency but not amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and an increase in the paired pulse ratio (PPR). This form of LTD is blocked by antagonists for CB1 and D2 dopamine receptors and impaired by blockers of L-type calcium channels. However, 10 Hz-induced LTD does not depend on postsynaptic depolarization, unlike HFS-induced LTD. Furthermore, this new form of LTD is not prevented by treatments known, to block HFS-induced LTD, including antagonism of metabotropic glutamate receptors (mGluRs), chelation of postsynaptic calcium, or intracellular application of an anandamide membrane transport inhibitor (VDM11). From these findings it is not clear that the endocannabinoid responsible for this form of LTD acts in a retrograde fashion, and the cellular source of endocannabinoid necessary for 10 Hz-induced LTD is as yet unknown. Our results demonstrate that a prolonged moderate frequency train induces cannabinoid-dependent LTD, further supporting the idea that endocannabinoids play a prominent role in the regulation of long-lasting changes in striatal output. C1 NIAAA, Lab Integrat Neurosci, DICBR, NIH, Rockville, MD 20852 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, DICBR, NIH, 5625 Fishers Lane,Room TS-13A, Rockville, MD 20852 USA. EM lovindav@mail.nih.gov NR 42 TC 59 Z9 63 U1 1 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2005 VL 562 IS 1 BP 245 EP 256 DI 10.1113/jphysiol.2004.068460 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 891OO UT WOS:000226590600025 PM 15498813 ER PT J AU Grant, BF Hasin, DS Stinson, FS Dawson, DA Chou, SP Ruan, WJ Huang, B AF Grant, BF Hasin, DS Stinson, FS Dawson, DA Chou, SP Ruan, WJ Huang, B TI Co-occurrence of 12-month mood and anxiety disorders and personality disorders in the US: results from the national epidemiologic survey on alcohol and related conditions SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE personality disorders; anxiety disorders; mood disorders; epidemiology; comorbidity ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; MAJOR DEPRESSION; AXIS-II; SOCIAL PHOBIA; COMORBIDITY; RELIABILITY; DIAGNOSES; MODULES; BIPOLAR AB The objective of this study was to determine the prevalence and co-occurrence of DSM-IV personality disorders (PDs) among individuals with current DSM-IV mood and anxiety disorders in the US population and among individuals who sought treatment for such mood or anxiety disorders. Face-to-face interviews were conducted with 43,093 individuals, 18 years and older, in the National Institute on alcohol abuse and alcoholism's 2001-2002 National epiderniologic survey on alcohol and related conditions (NESARC). Odds ratios (ORs) were calculated to determine the prevalence and associations between current DSM-IV axis I and axis II disorders. Associations between mood, anxiety and PDs were all positive and statistically significant. Avoidant and dependent PDs were more strongly related to mood and anxiety disorders than other PDs. Associations between obsessive-compulsive PD and mood and anxiety disorders were significant, but much weaker. Paranoid and schizoid PDs were most strongly related to dysthymia, mania, panic disorder with agoraphobia, social phobia and generalized anxiety disorder, while histrionic and antisocial PDs were most strongly related to mania and panic disorder with agoraphobia. Results of this study highlight the need for further research on overlapping symptomatology, factors giving rise to the associations and the treatment implications of these disorders when comorbid. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Dept HHS,NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Epidemiol, New York, NY 10027 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Dept HHS,NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 42 TC 191 Z9 196 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN PY 2005 VL 39 IS 1 BP 1 EP 9 DI 10.1016/j.jpsychires.2004.05.004 PG 9 WC Psychiatry SC Psychiatry GA 897VN UT WOS:000227033700001 PM 15504418 ER PT J AU Dorfel, D Werner, A Gerber, J von Kummer, R Schafer, M Karl, A AF Dorfel, D Werner, A Gerber, J von Kummer, R Schafer, M Karl, A TI Episodic memory functioning in PTSD - A fMRI study SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Technol, Dresden, Germany. NINDS, Washington, DC USA. RI Werner, 2509/C-4794-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2005 VL 19 IS 2 BP 113 EP 113 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 930KZ UT WOS:000229416000034 ER PT J AU Schaefer, M Heinze, HJ Rotte, M AF Schaefer, M Heinze, HJ Rotte, M TI Task-relevant modulation of primary somatosensory cortex: Evidence for a prefrontal-cortical sensory gating system SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD USA. Univ Magdeburg, Dept Neurol 2, D-39106 Magdeburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2005 VL 19 IS 2 BP 142 EP 142 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 930KZ UT WOS:000229416000160 ER PT J AU Halpern, CT King, RB Oslak, SG Udry, JR AF Halpern, CT King, RB Oslak, SG Udry, JR TI Body mass index, dieting, romance, and sexual activity in adolescent girls: Relationships over time SO JOURNAL OF RESEARCH ON ADOLESCENCE LA English DT Article ID WEIGHT-LOSS BEHAVIORS; SELF-ESTEEM; IMAGE; FEMALES; ATTITUDES; SYMPTOMS; SCHOOL; DISSATISFACTION; TESTOSTERONE; DEPRESSION AB Romantic relationships constitute an important, but understudied, developmental context for accommodation to pubertal change. Using a nationally representative sample of 5,487 black, white, and Hispanic adolescent females, this study examined associations among body mass index, current romantic involvement, and dieting. For each one point increase in body mass-index (BMI), the probability of having a romantic relationship decreased by 6%. Further, involvement in a nonsexual romantic relationship-but not involvement in a sexual romantic relationship-was associated with a significant increase in the likelihood of dieting. Associations between relationship type and dieting did not vary by age, socioeconomic status, or race, but were stronger at higher BMIs. These findings confirm that weight has implications for romantic involvement, which is highly valued by adolescent girls, and that romantic relationships, in turn, are important contexts in which to consider psychological and behavioral accommodation to the physical changes of puberty. C1 Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC 27599 USA. NICHHD, Bethesda, MD 20892 USA. RP Halpern, CT (reprint author), Univ N Carolina, Dept Maternal & Child Hlth, Rosenau Bldg,CB 7445, Chapel Hill, NC 27599 USA. EM carolyn_halpern@unc.edu NR 45 TC 34 Z9 34 U1 1 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1050-8392 J9 J RES ADOLESCENCE JI J. Res. Adolesc. PY 2005 VL 15 IS 4 BP 535 EP 559 DI 10.1111/j.1532-7795.2005.00110.x PG 25 WC Family Studies; Psychology, Developmental SC Family Studies; Psychology GA 987LD UT WOS:000233518500011 ER PT J AU Ward, MM AF Ward, MM TI Severity of illness in patients with systemic lupus erythematosus hospitalized at academic medical centers SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic lupus erythematosus; hospitalization; comorbidity; academic health center ID NONTEACHING HOSPITALS; REFERRAL BIAS; TEACHING HOSPITALS; DIAGNOSIS; MORTALITY; QUALITY; COST; CARE AB Objective. To compare the severity of illness of patients with systemic lupus erythematosus (SLE) between those hospitalized at academic medical centers and those hospitalized at community hospitals. Methods. In this population based cross-sectional survey, data on all hospitalizations of patients with SLE in California, New York, and Pennsylvania in 2000 were obtained from discharge abstracts submitted by acute care hospitals to state health planning agencies. Patients hospitalized at one of 36 academic medical centers in these states (N = 2072) were compared to patients hospitalized at community hospitals (N = 9373). The primary measures of severity of illness were the SLE Comorbidity Index, a weighted index of SLE manifestations and comorbid medical conditions based on discharge diagnoses, and long lengths of stay, defined as stays that exceeded the 90th percentile of hospital stays in the same diagnosis-related group in the United States. Results. Compared to patients at community hospitals, patients at academic medical centers had substantially higher scores on the SLE Comorbidity Index (odds ratio for each 1-point increase 1.27, 95% confidence interval 1.15-1.40, p < 0.0001) and were more likely to have long lengths of stay (OR 1.65, 95% CI 1.42-1.91, p < 0.0001). Patients at academic medical centers also had higher scores on the SLE Comorbidity Index (OR for each 1-point increase 1.16, 95% CI 1.07-1.27, p = 0.0002) and were more likely to have long lengths of stay (OR 1.27, 95% CI 1.08-1.49, p = 0.004) compared to patients at large (greater than or equal to 300 beds) community hospitals in the same metropolitan areas. Results for the SLE Comorbidity Index were similar in the subset of patients with SLE as the primary discharge diagnosis. Conclusion. Patients with SLE hospitalized at academic medical centers are generally more severely ill than those hospitalized at community hospitals, including large community hospitals in the same area. C1 NIH NIAMS IRP, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIH NIAMS IRP, Bldg 10,Room 9S205,10 Ctr Dr, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 33 TC 4 Z9 5 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2005 VL 32 IS 1 BP 27 EP 33 PG 7 WC Rheumatology SC Rheumatology GA 885HP UT WOS:000226148000007 PM 15630720 ER PT J AU Lipsky, PE AF Lipsky, PE TI Integrating biologic therapy into the comprehensive care of patients with rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Conference on Frontiers in Inflammatory Joint Diseases CY MAY 07-09, 2004 CL Toronto, CANADA DE biologic therapy; rheumatoid arthritis ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; MUCKLE-WELLS-SYNDROME; DOUBLE-BLIND; METHOTREXATE; MULTICENTER; DISABILITY; INFLIXIMAB; ANAKINRA; DAMAGE AB The advent of biologic therapy has not only provided the opportunity for better care of patients with rheumatoid arthritis (RA), but also has permitted a better understanding of the pathogenesis of this autoimmune/inflammatory disease. The capacity of these agents to suppress signs and symptoms as well as radiographic progression of RA strongly indicates that they can alter the course of the disease. Appropriate analysis of the effect of biologics should provide new insight into the role of the specific targeted molecules in rheumatoid inflammation, and provide information about means to optimize therapy with these highly potent therapeutics. C1 NIAMSD, Intramural Res Program, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Intramural Res Program, 9000 Rockville Pike,Bldg 10,Room 9N228, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2005 VL 32 SU 72 BP 54 EP 57 PG 4 WC Rheumatology SC Rheumatology GA 886OL UT WOS:000226238100018 ER PT J AU Severy, LJ Newcomer, S AF Severy, LJ Newcomer, S TI Critical issues in contraceptive and STI acceptability research SO JOURNAL OF SOCIAL ISSUES LA English DT Article ID FEMALE CONDOM; UNINTENDED PREGNANCY; HIV; WOMEN; PREVENTION; FERTILITY; BEHAVIOR; COUPLES; AIDS; INTERVENTION AB We review conceptual issues and theoretical frameworks related to users' acceptability of new technologies designed to protect reproductive health and prevent unwanted pregnancy. Special attention is given to distinctions among different kinds of users' perspectives regarding acceptability, as well as differentiating acceptability from assessments of the efficacy of innovative methods. Emphasis is also given to the larger context of couple decision-making and cultural variation. We argue that concern for sexual pleasure plays a central role in determining user perspectives regarding new methods. The female condom, contraceptive ring, contraceptive skin patch, microbicides, vaccines, emergency contraception, and PERSONA are discussed within the context of the identified critical issues. C1 Univ Florida, Gainesville, FL 32611 USA. Family Hlth Int, Gainesville, FL USA. NICHHD, Bethesda, MD 20892 USA. RP Severy, LJ (reprint author), POB 13950, Res Triangle Pk, NC 27709 USA. EM LSevery@fhi.org NR 66 TC 49 Z9 50 U1 4 U2 6 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0022-4537 J9 J SOC ISSUES JI J. Soc. Issues PY 2005 VL 61 IS 1 BP 45 EP 65 DI 10.1111/j.0022-4537.2005.00393.x PG 21 WC Social Issues; Psychology, Social SC Social Issues; Psychology GA 901UA UT WOS:000227306200003 ER PT J AU Zheng, G Park, S AF Zheng, G Park, S TI Another look at life testing SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE efficiency; Fisher information; hazard function; time saving; type I censoring; type II censoring ID FISHER INFORMATION; WEIBULL DISTRIBUTION; ORDER-STATISTICS; HAZARD RATE AB In life testing, n identical testing items are placed on test. Instead of doing a complete life testing with all n outcomes, a Type II censored life testing, consisting of the first m outcomes, is usually employed. Although statistical analysis for the life testing based on censored data is less efficient than the complete life testing, the expected length of the censored life testing is less than that of the complete life testing. In this paper, we compare censored and complete life testing and suggest ways to improve time saving and efficiency. Instead of doing a complete life testing with all n outcomes, we put N > n items on test, which continues until we observe the nth outcome. With both the censored life testing and the complete life testing containing the same number of observations, we show that the expected length of the censored life testing is less than that of the complete life testing and that the censored life testing may be also more efficient than the complete life testing with the same number of observations. (C) 2003 Elsevier B.V. All rights reserved. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Yonsei Univ, Dept Appl Stat, Seoul 120749, South Korea. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Rockledge 2,6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhibi.nih.gov; sangun@yonsei.ac.kr NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JAN 1 PY 2005 VL 127 IS 1-2 BP 103 EP 117 DI 10.1016/j.jspi.2003.08.007 PG 15 WC Statistics & Probability SC Mathematics GA 866PF UT WOS:000224784700006 ER PT J AU Simons-Morton, B Chen, RS AF Simons-Morton, B Chen, RS TI Latent growth curve analyses of parent influences on drinking progression among early adolescents SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID ALCOHOL-USE; SUBSTANCE USE; PROTECTIVE FACTORS; PROBLEM BEHAVIOR; PEER INFLUENCES; ASSOCIATION; SMOKING; ONSET; EXPECTANCIES; INVOLVEMENT AB Objective: The nature of parent influences on early adolescent substance use was examined. Method: Latent growth curve analyses were used to examine data on a sample of 2,453 adolescents from seven middle schools who were randomized to a problem behavior prevention program or a control condition and were assessed a total of five times during sixth to ninth grade. Results: Whereas the growth in the number of friends who drink was positively associated with adolescent drinking, parental involvement, monitoring and expectations over time provided direct protective effects against drinking progression and indirect effects by limiting increases in the number of friends who drink. Conclusions: The results provide evidence in a sample of early adolescents that parenting behavior-including involvement, monitoring and expectations protected against progression in drinking directly as well as indirectly by limiting growth in the number of friends who drink. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat Prevent Res, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat Prevent Res, 6100 Execut Blvd,7B13M, Bethesda, MD 20892 USA. EM Mortonb@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [N01-HD-4-3207] NR 31 TC 46 Z9 48 U1 2 U2 4 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JAN PY 2005 VL 66 IS 1 BP 5 EP 13 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 906SM UT WOS:000227663100001 PM 15830898 ER PT J AU Purow, B Staveley-O'Carroll, K AF Purow, B Staveley-O'Carroll, K TI Targeting of vaccinia virus using biotin-avidin viral coating and biotinylated antibodies SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE vaccinia; tropism; targeting; biotin; avidin ID RETROVIRAL VECTORS; RECOMBINANT VECTOR; ADENOVIRUS; RECEPTOR; MVA; EXPRESSION; THERAPY; TROPISM; CELLS; MICE AB Introduction. To test a general method for altering the tropism of viral vectors, we conjugated targeting antibody to the surface of recombinant vaccinia virus with a biotin-avidin-biotin linker and assessed the resulting infectivity in target cells and controls. Materials and methods. We biotinylated a vaccinia viral vector and used avidin to crosslink the biotinylated viral surface to a biotinylated antibody specific for a molecule on the surface of a target cell. In an in vitro model system, we coated a recombinant vaccinia construct containing the E. coli beta-galactosidase gene with antibody to the murine class I MHC molecule D-b. Target cells were B78H1 murine melanoma cells transduced with either the Db gene or, as a control, the K-b gene. Infectivity was assessed by staining target cells with x-gal to demonstrate expression of virally delivered beta-galactosidase. This technique was also assessed in a second system with vaccinia/beta-gal targeted to the murine B7.2 molecule. The infectivity of the resulting construct was assessed for murine SA1 fibrosarcoma cells transfected with the B7.2 gene and for wild-type, B7.2-negative SA1. Experiments were repeated in each system with similar results. Results. This strategy demonstrated antibody-mediated viral targeting in both the B78H1 and the SA1 models. Importantly, addition of the targeting coat diminished the infectivity of the modified vaccinia for control cells but preserved infectivity for targeted cells. In the B78H1 system, Dh-targeted vaccinia consistently had 2- to 3-fold greater infectivity for B78H1D(b) than B78H1K(b). Increasing the number of avidin molecules used per virion in the synthesis of the viral coat led to greater selectivity but decreased overall infectivity. In the SA1 system, B7.2-targeted vaccinia demonstrated completely ablated infectivity for control SA1 cells, but maintained infectivity for target SA1/B7.2 cells. Conclusions. Recombinant viral vectors such as vaccinia may be coated with biotin/avidin and linked to biotinylated antibodies to preferentially target specific cell types in vitro. Such an approach may be useful in targeting recombinant lytic viruses to tumors for destruction and in immune up-regulation in vivo. Similarly, this approach may enhance nonlytic viruses for gene therapy applications. (C) 2004 Elsevier Inc. All rights reserved. C1 NCI, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. RP Purow, B (reprint author), Milton S Hershey Med Ctr, Dept Surg, 500 Univ Dr,H149, Hershey, PA 17033 USA. EM KSOC@psu.edu NR 24 TC 14 Z9 14 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JAN PY 2005 VL 123 IS 1 BP 49 EP 54 DI 10.1016/j.jss.2004.04.022 PG 6 WC Surgery SC Surgery GA 892UD UT WOS:000226674600008 PM 15652950 ER PT J AU March, J Silva, S Petrycki, S Curry, J Wells, K Fairbank, J Burns, B Domino, M McNulty, S Casat, C Kolker, J Riedal, K Goldman, M Feeny, N Findling, R Stull, S McNamara, N Weller, E Robins, M Weller, R Jessani, N Waslick, B Sweeney, M Kandel, R Schoenholz, D Walkup, J Ginsburg, G Kastelic, E Koo, H Kratochvil, C May, D LaGrone, R Harrington, M Albano, AM Hirsch, G Knibbs, T Capili, E Reinecke, M Leventhal, B Nageotte, C Rogers, G Pathak, S Wells, J Arszman, S Danielyan, A Simons, A Rohde, P Grimm, J Nguyen, L Emslie, G Kennard, B Hughes, C Ruberu, M Benazon, N Butkus, M Bartoi, M Clarke, G Brent, D Koch, G Greenhouse, J Johnson, R Leckman, J Lewis, L Marcus, SM Rochon, J Stark, K AF March, J Silva, S Petrycki, S Curry, J Wells, K Fairbank, J Burns, B Domino, M McNulty, S Casat, C Kolker, J Riedal, K Goldman, M Feeny, N Findling, R Stull, S McNamara, N Weller, E Robins, M Weller, R Jessani, N Waslick, B Sweeney, M Kandel, R Schoenholz, D Walkup, J Ginsburg, G Kastelic, E Koo, H Kratochvil, C May, D LaGrone, R Harrington, M Albano, AM Hirsch, G Knibbs, T Capili, E Reinecke, M Leventhal, B Nageotte, C Rogers, G Pathak, S Wells, J Arszman, S Danielyan, A Simons, A Rohde, P Grimm, J Nguyen, L Emslie, G Kennard, B Hughes, C Ruberu, M Benazon, N Butkus, M Bartoi, M Clarke, G Brent, D Koch, G Greenhouse, J Johnson, R Leckman, J Lewis, L Marcus, SM Rochon, J Stark, K CA TADS Team TI The treatment for adolescents with depression study (TADS): Demographic and clinical characteristics SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; CONTROLLED-TRIAL; MAJOR DEPRESSION; HEALTH-CARE; FOLLOW-UP; CHILDREN; DISORDERS; EFFICACY; RELIABILITY; FLUOXETINE AB Objective: The Treatment for Adolescents With Depression Study is a multicenter, randomized clinical trial sponsored by the NIMH. This study is designed to evaluate the short- and long-term effectiveness of four treatments for adolescents with major depressive disorder: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely, pill placebo. This report describes the demographic and clinical characteristics of the sample and addresses external validity. Method: Participants are 439 adolescents, aged 12-17 years inclusively, with a primary DSM-IV diagnosis of current major depressive disorder. Baseline data are summarized and compared with those from national samples and previous trials. Results: The sample composition is 54.4% girls, 73.8% white, 12.5% African American, and 8.9% Hispanic. The mean Child Depression Rating Scale-Revised total score is 60.1 (SD = 10.4, range 45-98) with 86.0% experiencing their first major depressive episode. The most common concurrent diagnoses are generalized anxiety disorder (15.3%), attention-deficit/hyperactivity disorder (13.7%), oppositional defiant disorder (13.2%), social phobia (10.7%), and dysthymia (10.5%). Demographic results are consistent with data from national samples and large psychopharmacology trials involving depressed adolescents. Conclusions: The Treatment for Adolescents With Depression Study provides a large, diverse, and representative sample of depressed adolescents that highlights the complexity of major depressive disorder in adolescents and provides a rich source for explicating the effects of moderator and mediator variables on baseline psychopathology and treatment outcome. C1 Duke Clin Res Inst, Durham, NC 27710 USA. Duke Univ, Ctr Med, Dept Psychiat & Behav Sci, NIMH, Rockville, MD USA. Duke Univ, Ctr Med, Duke Clin Res Inst, Rockville, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY 10027 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Nebraska, Lincoln, NE 68583 USA. NYU, New York, NY USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Univ Oregon, Eugene, OR 97403 USA. Wayne State Univ, Detroit, MI 48202 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Silva, S (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27710 USA. EM silva007@mc.duke.edu RI Fairbank, John/F-8972-2013 OI Fairbank, John/0000-0003-2604-7256 NR 53 TC 4 Z9 4 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2005 VL 44 IS 1 BP 28 EP 40 DI 10.1097/01.chi.0000145807.09027.82 PG 13 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 880WU UT WOS:000225821500005 ER PT J AU Spenny, ML Suwannarat, P Gahl, WA Cowen, EW AF Spenny, ML Suwannarat, P Gahl, WA Cowen, EW TI Blue pigmentation and arthritis in an elderly man SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ALKAPTONURIA; ACID C1 NCI, Dermatol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD USA. RP Cowen, EW (reprint author), NCI, Dermatol Branch, Canc Res Ctr, Bldg 10 Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM cowene@mail.nih.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2005 VL 52 IS 1 BP 122 EP 124 DI 10.1016/j.jaad.2004.09.011 PG 3 WC Dermatology SC Dermatology GA 886PH UT WOS:000226240300015 PM 15627089 ER PT J AU Brenes, GA Guralnik, JM Williamson, JD Fried, LP Simpson, C Simonsick, EM Penninx, BWJH AF Brenes, GA Guralnik, JM Williamson, JD Fried, LP Simpson, C Simonsick, EM Penninx, BWJH TI The influence of anxiety on the progression of disability SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE anxiety symptoms; disability; aged ID DISABLED OLDER WOMEN; GENERALIZED ANXIETY; FUNCTIONAL STATUS; LONGITUDINAL EVIDENCE; PHYSICAL-DISABILITY; EMOTIONAL VITALITY; HIP FRACTURE; PRIMARY-CARE; RISK-FACTORS; DEPRESSION AB OBJECTIVES: To determine the influence of anxiety on the progression of disability and examine possible mediators of the relationship. DESIGN: Community-based observational study. SETTING: Women's Health and Aging Study I, a prospective observational study with assessments every 6 months for 3 years. PARTICIPANTS: One thousand two functionally limited women aged 65 and older. MEASUREMENTS: Anxiety symptoms were assessed using four questions from the Hopkins Symptom Checklist (nervous or shaky, avoidance of certain things, tense or keyed up, fearful). Participants who reported experiencing two or more of these symptoms at baseline were considered anxious. Anxiety as a predictor of the onset of four types of disability was examined using Cox proportional hazards models. Three models were tested: an unadjusted model, a model adjusted for confounding variables (age, race, vision, number of diseases, physical performance, depressive symptoms), and a mediational model (benzodiazepine and psychotropic medication use, physical activity, emotional support). RESULTS: Nineteen percent of women reported two or more symptoms of anxiety at baseline. Unadjusted models indicate that anxiety was associated with a greater risk of worsening disability: activity of daily living (ADL) disability (relative risk (RR)=1.40, 95% confidence interval (CI)=1.10-1.79), mobility disability (RR=1.41, 95% CI=1.06-1.86), lifting disability (RR=1.54, 95% CI=1.20-1.97), and light housework disability (RR=1.77, 95% CI=1.32-2.37). After adjusting for confounding variables, anxiety continued to predict the development of two types of disability: ADL disability (RR=1.41, 95% CI=1.08-1.84) and light housework disability (RR=1.56, 95% CI=1.14-2.14). Finally, benzodiazepine and psychotropic medication use, physical activity, and emotional support were not significant mediators of the effect of anxiety on the development of a disability. CONCLUSION: Anxiety is a significant risk factor for the progression of disability in older women. Studies are needed to determine whether treatment of anxiety delays or prevents disability. C1 Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Brenes, GA (reprint author), Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Med Ctr Blvd, Winston Salem, NC 27109 USA. EM gbrenes@wfubmc.edu FU NIA NIH HHS [AG-09834, N01-AG-12112, R01 AG009834]; NIMH NIH HHS [MH65281, K23 MH065281] NR 38 TC 62 Z9 65 U1 1 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2005 VL 53 IS 1 BP 34 EP 39 DI 10.1111/j.1532-5415.2005.53007.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 882PU UT WOS:000225951600005 PM 15667373 ER PT J AU Raisch, DW Fudala, PJ Saxon, AJ Walsh, R Casadonte, P Ling, W Johnson, BA Malkerneker, U Ordorica, P Williford, WO Sather, MR AF Raisch, DW Fudala, PJ Saxon, AJ Walsh, R Casadonte, P Ling, W Johnson, BA Malkerneker, U Ordorica, P Williford, WO Sather, MR TI Pharmacists' and technicians' perceptions and attitudes toward dispensing buprenorphine/naloxone to patients with opioid dependence SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Pharmacists-Association CY MAR 28-APR 01, 2003 CL New Orleans, LA SP Amer Pharmacists Assoc DE opioid dependence; buprenorphine; naloxone; community and ambulatory pharmacy; pharmaceutical care; prescription forgery; drug diversion; attitudes; perceptions ID OPIATE ADDICTION; PAIN; NALOXONE AB Objective: To assess the perceptions and attitudes of pharmacists and pharmacy technicians involved in an office-based opioid dependence treatment program using buprenorphine/naloxone. Design: Cross-sectional attitudinal assessment. Setting: Community, outpatient hospital, and clinic pharmacies. Participants: Pharmacists and technicians participating in a clinical trial of opioid dependence treatment using buprenorphine/naloxone. Intervention: Written and telephone surveys followed by interviews with open-ended items. Main Outcome Measures: Attitudes and perceptions regarding opioid dependent patients and use of buprenorphine/naloxone for treatment of opioid dependence. Results: Pharmacies in seven states (New York, Virginia, Illinois, Florida, Texas, California, and Washington) participated in the clinical trial. A total of 40 pharmacists and pharmacy technicians responded to the initial written survey, representing 27 of the 32 pharmacies (84%). Follow-up interviews were obtained from one individual at 30 of those pharmacies (93.8%). Most pharmacy personnel (77.5%) involved with this study were not more concerned about theft or break-ins and would be willing to participate in opioid dependence treatment as the medication became available commercially (70%). The majority of respondents (85%) indicated that patients did not cause problems at their pharmacies. Compared with their experiences in administering other narcotic medications, most respondents did not express increased concern regarding prescription forgery (75%) or diversion (80%) of buprenorphine/naloxone. Conclusion: The majority of respondents expressed positive attitudes and perceptions regarding patients treated for opioid dependence with buprenorphine/naloxone. C1 Clin Res Pharm Coordinating Ctr, Vet Affairs Cooperat Studies Program, Albuquerque, NM 87106 USA. Vet Affairs Med Ctr, Albuquerque, NM 87106 USA. Vet Affairs Puget Sound Hlth Care Syst, Addict Patient Care Line, Albuquerque, NM USA. NIDA, Div Treatment Res & Dev, Regulatory Affairs Branch, NIH, Bethesda, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Integrated Substance Abuse Programs, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Virginia, Dept Psychiat Med, Charlottesville, VA USA. Hines Vet Affairs Med Ctr, Chicago, IL USA. James A Haley Vet Hosp, Mental Hlth & Behav Sci Serv, Tampa, FL USA. RP Raisch, DW (reprint author), Clin Res Pharm Coordinating Ctr, Vet Affairs Cooperat Studies Program, 2401 Ctr, Albuquerque, NM 87106 USA. EM dennis.raisch@csp.research.med.va.gov FU NIDA NIH HHS [3Y01-DA030011-04] NR 20 TC 10 Z9 11 U1 4 U2 4 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSN JI J. Am. Pharm. Assoc. PD JAN-FEB PY 2005 VL 45 IS 1 BP 23 EP 32 DI 10.1331/1544345052843200 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 915TK UT WOS:000228333900009 PM 15730114 ER PT J AU Okada, H Kikuta, T Kobayashi, T Inoue, T Kanno, Y Takigawa, M Sugaya, T Kopp, JB Suzuki, H AF Okada, H Kikuta, T Kobayashi, T Inoue, T Kanno, Y Takigawa, M Sugaya, T Kopp, JB Suzuki, H TI Connective tissue growth factor expressed in tubular epithelium plays a pivotal role in renal fibrogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; VASCULAR ENDOTHELIAL-CELLS; FIBROBLAST-LIKE CELLS; TUBULOINTERSTITIAL FIBROSIS; MESANGIAL CELLS; EXPERIMENTAL GLOMERULONEPHRITIS; DIABETIC-NEPHROPATHY; GOODPASTURE-SYNDROME; RAT-KIDNEY; IN-VIVO AB Connective tissue growth factor (CTGF) is one of the candidate factors that are thought to mediate the downstream profibrotic action of TGF-beta. However, its precise role in renal interstitial fibrogenesis has not yet been clarified. It was demonstrated previously that CTGF was expressed in tubular epithelial cells that had been engulfed by interstitial fibrosis in the remnant kidney of the subtotal nephrectomy (SNx) model. In the present study, co-cultures of tubular epithelial cells (mProx24) and tubulointerstitial fibroblasts (TFB) that mimic the subepithelial mesenchyme in the kidney were used to study the profibrotic effects of TGF-beta1-induced CTGF. In these co-cultures, TGF-beta1 treatment resulted in significantly increased mRNA levels of type I collagen and fibronectin in the TFB. These effects were both direct and indirect, with the latter being mediated by CTGF derived from the co-cultured mProx24. Then TGF-beta1 transgenic mice were subtotally nephrectomized and treated with CTGF antisense oligodeoxynucleotide, and their kidneys were analyzed for fibrosis. Intravenous administration of CTGF antisense oligodeoxynucleotide significantly blocked CTGF expression in the proximal tubular epithelial cells in the remnant kidney of these animals despite the sustained level of TGF-beta1 mRNA. This reduction in CTGF mRNA level paralleled a reduction in mRNA levels of matrix molecules as well as proteinase inhibitors plasminogen activator inhibitor-1 and tissue inhibitor of metalloproteinase-1, suppressing renal interstitial fibrogenesis. In conclusion, tubular CTGF acts as a downstream mediator of the profibrotic effects of TGF-beta1 in the remnant kidney, which is a promising target for antifibrotic drugs designed to treat TGF-beta1- dependent interstitial fibrosis. C1 Saitama Med Coll, Dept Nephrol, Moroyama, Saitama 3500495, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Biochem & Mol Dent, Okayama, Japan. Univ Tsukuba, Inst Appl Biochem, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki, Japan. NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Suzuki, H (reprint author), Saitama Med Coll, Dept Nephrol, 38 Morohongo, Moroyama, Saitama 3500495, Japan. EM iromichi@saitama-med.ac.jp OI Kopp, Jeffrey/0000-0001-9052-186X NR 37 TC 117 Z9 143 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2005 VL 16 IS 1 BP 133 EP 143 DI 10.1681/ASN.2004040339 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 883JZ UT WOS:000226008700019 PM 15574513 ER PT J AU Coresh, J Byrd-Holt, D Astor, BC Briggs, JP Eggers, PW Lacher, DA Hostetter, TH AF Coresh, J Byrd-Holt, D Astor, BC Briggs, JP Eggers, PW Lacher, DA Hostetter, TH TI Chronic kidney disease awareness, prevalence, and trends among US adults, 1999 to 2000 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; GLOMERULAR-FILTRATION RATE; HIGH BLOOD-PRESSURE; UNITED-STATES; SERUM CREATININE; CARDIOVASCULAR-DISEASE; POPULATION; INSUFFICIENCY AB The incidence of kidney failure treatment in the United States increased 57% from 1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults surveyed in 1988 to 1994. The objective of this study was to estimate awareness of CKD in the U.S. population during 1999 to 2000 and to determine whether the prevalence of CKD in the United States increased compared with 1988 to 1994. Analysis was conducted of nationally representative samples of noninstitutionalized adults, aged 20 yr and older, in two National Health and Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to 2000 (n = 4101) for prevalence SE. Awareness of CKD is self-reported. Kidney function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation. Self-reported awareness of weak or failing kidneys in 1999 to 2000 was strongly associated with decreased kidney function and albuminuria but was low even in the presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59 ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3% at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)), awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%; P = 0.008). The prevalence of moderately or severely decreased kidney function (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/- 0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same time, the prevalence of albuminuria (ACR 2: 30 mg/g) in single spot urine increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence was similar in both surveys (9% using ACR > 30 mg/g for persistent microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender-specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S. population is low. In contrast to the dramatic increase in treated kidney failure, overall CKD prevalence in the U.S. population has been relatively stable. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Soc & Sci Syst Inc, Silver Spring, MD USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Surveys, Hyattsville, MD 20782 USA. RP Coresh, J (reprint author), 2024 E Monument St, Baltimore, MD 21205 USA. EM coresh@jhu.edu RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NCRR NIH HHS [5M01RR00722, RR00035]; NIDDK NIH HHS [1R21DK67651, N01-DK-1-2478] NR 31 TC 476 Z9 497 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2005 VL 16 IS 1 BP 180 EP 188 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 883JZ UT WOS:000226008700025 PM 15563563 ER PT J AU Cantor, D AF Cantor, D TI Between Galen, Geddes, and the Gael: Arthur Brock, modernity, and medical humanism in early-twentieth-century Scotland SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Article; Proceedings Paper CT Meeting of the Society-for-the-History-of-Medicine CY MAR 14, 2002 CL Washington, DC SP Soc Hist Med DE Arthur J. Brock; Patrick Geddes; ancient Greece; ancient medicine; "Back to the land," cancer; Celtic revivalism; classical revivalism; Craiglockhart War Hospital; Edinburgh; ergotherapy; Gael; medical humanism; medical sociology; neurasthenia; North Queensferry; Scotland; shell shock; Wilfred Owen ID BRITAIN AB Arthur Brock (1879-1947) is generally remembered as the physician who treated poet Wilfred Owen for shell shock and as the translator of Galen and other ancient physicians. He was also a key figure in the early-twentieth-century humanist revival within medicine. Brock's interest in humanism, I argue, was inspired by a broader concern about modernity and by a desire to return medicine and society to the more harmonious. organic existence that he believed was characteristic of ancient Greece and could still be found among "primitive" peoples, such as the Scottish Gaels. This article explores Brock's anxieties about modernity and its relations to his interests in ancient and "primitive" peoples; to his medical thought and practice; to his interests in history, sociology, language, and translation; and to his involvement in the social and political life of Edinburgh and North Queensferry, where he moved in 1925. Crucially:. it shows how all these interests and activities were influenced by Brock's mentor, Edinburgh polymath Patrick Geddes. The article concludes with a discussion of Brock's. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), NCI, Div Canc Prevent, Execut Plaza N,Suite 2025, Bethesda, MD 20892 USA. EM cantord@mail.nih.gov NR 180 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JAN PY 2005 VL 60 IS 1 BP 1 EP 41 DI 10.1093/jhmas/jri001 PG 41 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 879UY UT WOS:000225745600001 PM 15583214 ER PT J AU Baker, SG Izmirlian, G Kipnis, V AF Baker, SG Izmirlian, G Kipnis, V TI Resolving paradoxes involving surrogate end points SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE prentice criterion ID TRIALS AB We define a surrogate end point as a measure or indicator of a biological process that is obtained sooner, at less cost or less invasively than a true end point of health outcome and is used to make conclusions about the effect of an intervention on the true end point. Prentice presented criteria for valid hypothesis testing of a surrogate end point that replaces a true end point. For using the surrogate end point to estimate the predicted effect of intervention on the true end point, Day and Duffy assumed the Prentice criterion and arrived at two paradoxical results: the estimated predicted intervention effect by using a surrogate can give more precise estimates than the usual estimate of the intervention effect by using the true end point and the variance is greatest when the surrogate end point perfectly predicts the true end point. Begg and Leung formulated similar paradoxes and concluded that they indicate a flawed conceptual strategy arising from the Prentice criterion. We resolve the paradoxes as follows. Day and Duffy compared a surrogate-based estimate of the effect of intervention on the true end point with an estimate of the effect of intervention on the true end point that uses the true end point. Their paradox arose because the former estimate assumes the Prentice criterion whereas the latter does not. If both or neither of these estimates assume the Prentice criterion, there is no paradox. The paradoxes of Begg and Leung, although similar to those of Day and Duffy, arise from ignoring the variability of the parameter estimates irrespective of the Prentice criterion and disappear when the variability is included. Our resolution of the paradoxes provides a firm foundation for future meta-analytic extensions of the approach of Day and Duffy. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Div Canc Prevent, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 8 TC 10 Z9 10 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0964-1998 J9 J ROY STAT SOC A STA JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2005 VL 168 BP 753 EP 762 DI 10.1111/j.1467-985X.2005.00373.x PN 4 PG 10 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 968NI UT WOS:000232168800008 ER PT J AU Huang, LS Wang, HK Cox, C AF Huang, LS Wang, HK Cox, C TI Assessing interaction effects in linear measurement error models SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE asymptotic normality; interaction; regression calibration; simulation extrapolation ID EXPOSURE; METHYLMERCURY AB In a linear model, the effect of a continuous explanatory variable may vary across groups defined by a categorical variable, and the variable itself may be subject to measurement error. This suggests a linear measurement error model with slope-by-factor interactions. The variables that are defined by such interactions are neither continuous nor discrete, and hence it is not immediately clear how to fit linear measurement error models when interactions are present. This paper gives a corollary of a theorem of Fuller for the situation of correcting measurement errors in a linear model with slope-by-factor interactions. In particular, the error-corrected estimate of the coefficients and its asymptotic variance matrix are given in a more easily assessable form. Simulation results confirm the asymptotic normality of the coefficients in finite sample cases. We apply the results to data from the Seychelles Child Development Study at age 66 months, assessing the effects of exposure to mercury through consumption of fish on child development for females and males for both prenatal and post-natal exposure. C1 Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. NIH, Bethesda, MD 20892 USA. RP Huang, LS (reprint author), Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, 601 Elmwood Ave,Box 630, Rochester, NY 14642 USA. EM Lhuang@bst.rochester.edu NR 7 TC 9 Z9 9 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD JAN PY 2005 VL 54 BP 21 EP 30 DI 10.1111/j.1467-9876.2005.00467.x PN 1 PG 10 WC Statistics & Probability SC Mathematics GA 864PL UT WOS:000224645300002 ER PT J AU Peddada, SD Dinse, GE Haseman, JK AF Peddada, SD Dinse, GE Haseman, JK TI A survival-adjusted quantal response test for comparing tumour incidence rates SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE animal carcinogenicity study; cancer bioassay; Cochran-Armitage trend test; National Toxicology Program; order-restricted inference; poly-3 test; tumour onset ID ANIMAL TUMORIGENICITY DATA; TREND TESTS; CARCINOGENICITY AB The paper presents a case-study of skin fibromas among male rats in the 2-year cancer bioassay of methyleugenol that was conducted by the US National Toxicology Program (NTP). In animal carcinogenicity experiments such as this one, tumour rates are often compared with the Cochran-Armitage (CA) trend test. The operating characteristics of the CA test, however, can be adversely affected by survival differences across groups and by the assumed dose metric. Survival-adjusted generalizations of the CA test have been proposed, but they are still sensitive to the choice of scores that are assigned to the dose groups. We present an alternative test, which outperforms the survival-adjusted CA test which is currently used by the NTP to compare incidence rates. Simulated data from a wide range of realistic situations show that the operating characteristics of the test proposed are superior to those of the NTP's survival-adjusted CA test, especially for rare tumours and wide logarithmic spacings of the dose metric. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 NR 17 TC 10 Z9 10 U1 1 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD JAN PY 2005 VL 54 BP 51 EP 61 DI 10.1111/j.1467-9876.2005.00469.x PN 1 PG 11 WC Statistics & Probability SC Mathematics GA 864PL UT WOS:000224645300004 ER PT J AU Cox, C AF Cox, C TI Limits of quantitation for laboratory assays SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE calibration; delta method; detection limit; limit of quantitation; linear regression ID REGRESSION METHODS; FIELLER THEOREM; CALIBRATION; DECISION AB A common problem with laboratory assays is that a measurement of a substance in a test sample becomes relatively imprecise as the concentration decreases. A standard solution is to establish lower limits for reliable measurement. A quantitation limit is a level above which a measurement has sufficient precision to be reliably reported. The paper proposes a new approach to defining the limit of quantitation for the case where a linear calibration curve is used to estimate actual concentrations from measured values. The approach is based on the relative precision of the estimated concentration, using the delta method to approximate the precision. A graphical display is proposed for the assessment of estimated concentrations, as well as the overall reliability of the calibration curve. Our research is motivated by a clinical inhalation experiment. Comparisons are made between the approach proposed and two standard methods, using both real and simulated data. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Rochester, NY 14627 USA. RP Cox, C (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Room 7B05,6100 Execut Blvd, Bethesda, MD 20892 USA. EM coxchris@mail.nih.gov NR 18 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD JAN PY 2005 VL 54 BP 63 EP 76 DI 10.1111/j.1467-9876.2005.00470.x PN 1 PG 14 WC Statistics & Probability SC Mathematics GA 864PL UT WOS:000224645300005 ER PT J AU Elliott, MR Davis, WW AF Elliott, MR Davis, WW TI Obtaining cancer risk factor prevalence estimates in small areas: combining data from two surveys SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Behavioral Risk Factors Surveillance System; cigarette smoking; dual-frame estimation; mammogram; National Health Interview Survey; propensity scores ID HEALTH INTERVIEW SURVEY; COVERAGE; BREAST AB Cancer surveillance research requires accurate estimates of risk factors at the small area level. These risk factors are often obtained from surveys such as the National Health Interview Survey (NHIS) or the Behavioral Risk Factors Surveillance System (BRFSS). The NHIS is a nationally representative, face-to-face survey with a high response rate; however, it cannot produce state or substate estimates of risk factor prevalence because the sample sizes are too small and small area identifiers are unavailable to the public. The BRFSS is a state level telephone survey that excludes non-telephone households and has a lower response rate, but it does provide reasonable sample sizes in all states and many counties and has publicly available small area identifiers (counties). We propose a novel extension of dual-frame estimation using propensity scores that allows the complementary strengths of each survey to compensate for the weakness of the other. We apply this method to obtain 1999-2000 county level estimates of adult male smoking prevalence and mammogram usage rates among females who were 40 years old and older. We consider evidence that these NHIS-adjusted estimates reduce the effects of selection bias and non-telephone coverage in the BRFSS. Data from the Current Population Survey Tobacco Use Supplement are also used to evaluate the performance of this approach. A hybrid estimator that selects one of the two estimators on the basis of the mean-square error is also considered. C1 Univ Penn, Med Ctr, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. RP Elliott, MR (reprint author), Univ Penn, Med Ctr, Dept Biostat & Epidemiol, 612 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM melliott@cceb.upenn.edu NR 30 TC 14 Z9 14 U1 2 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2005 VL 54 BP 595 EP 609 DI 10.1111/j.1467-9876.2005.05459.x PN 3 PG 15 WC Statistics & Probability SC Mathematics GA 915UJ UT WOS:000228336500007 ER PT J AU Albert, PS Shen, J AF Albert, PS Shen, J TI Modelling longitudinal semicontinuous emesis volume data with serial correlation in an acupuncture clinical trial SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE acupuncture; emesis; Monte Carlo EM; repeated measures; semicontinuous data; two-part models; volume data ID MAXIMUM-LIKELIHOOD; BINARY DATA; ZERO; ALGORITHMS AB In longitudinal studies, we are often interested in modelling repeated assessments of volume over time. Our motivating example is an acupuncture clinical trial in which we compare the effects of active acupuncture, sham acupuncture and standard medical care on chemotherapy-induced nausea in patients being treated for advanced stage breast cancer. An important end point for this study was the daily measurement of the volume of emesis over a 14-day follow-up period. The repeated volume data contained many 0s, had apparent serial correlation and had missing observations, making analysis challenging. The paper proposes a two-part latent process model for analysing the emesis volume data which addresses these challenges. We propose a Monte Carlo EM algorithm for parameter estimation and we use this methodology to show the beneficial effects of acupuncture on reducing the volume of emesis in women being treated for breast cancer with chemotherapy. Through simulations, we demonstrate the importance of correctly modelling the serial correlation for making conditional inference. Further, we show that the correct model for the correlation structure is less important for making correct inference on marginal means. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD USA. RP Albert, PS (reprint author), NCI, Biometr Res Branch, Room 8136,6130 Execut Blvd, Bethesda, MD 20892 USA. EM Albertp@ctep.nci.nih.gov NR 21 TC 13 Z9 13 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2005 VL 54 BP 707 EP 720 DI 10.1111/j.1467-9876.2005.05515.x PN 4 PG 14 WC Statistics & Probability SC Mathematics GA 944MB UT WOS:000230432000002 ER PT J AU Tiwari, RC Cronin, KA Davis, W Feuer, EJ Yu, BB Chib, S AF Tiwari, RC Cronin, KA Davis, W Feuer, EJ Yu, BB Chib, S TI Bayesian model selection for join point regression with application to age-adjusted cancer rates SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE annual percentage change; Bayes factor; Bayes information criterion; Markov chain Monte Carlo methods; permutation test ID MARGINAL LIKELIHOOD; SCHWARZ CRITERION; RANDOM-VARIABLES; GIBBS SAMPLER; INFERENCE; SEQUENCE; OUTPUT; TESTS AB The method of Bayesian model selection for join point regression models is developed. Given a set of K+1 join point models M-0, M-1, ..., M-K with 0, 1, ..., K join points respec-tively, the posterior distributions of the parameters and competing models M-k are computed by Markov chain Monte Carlo simulations. The Bayes information criterion BIC is used to select the model M-k with the smallest value of BIC as the best model. Another approach based on the Bayes factor selects the model M-k with the largest posterior probability as the best model when the prior distribution of M-k is discrete uniform. Both methods are applied to analyse the observed US cancer incidence rates for some selected cancer sites. The graphs of the join point models fitted to the data are produced by using the methods proposed and compared with the method of Kim and co-workers that is based on a series of permutation tests. The analyses show that the Bayes factor is sensitive to the prior specification of the variance sigma(2), and that the model which is selected by BIC fits the data as well as the model that is selected by the permutation test and has the advantage of producing the posterior distribution for the join points. The Bayesian join point model and model selection method that are presented here will be integrated in the National Cancer Institute's join point software (http://www.srab.cancer.gov/joinpoint/) and will be available to the public. C1 Informat Management Serv Inc, Silver Spring, MD 20904 USA. NCI, Rockville, MD USA. Washington Univ, St Louis, MO USA. RP Yu, BB (reprint author), Informat Management Serv Inc, Suite 200,12501 Prosper Dr, Silver Spring, MD 20904 USA. EM yub@imsweb.com NR 35 TC 32 Z9 32 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2005 VL 54 BP 919 EP 939 DI 10.1111/j.1467-9876.2005.00518.x PN 5 PG 21 WC Statistics & Probability SC Mathematics GA 968NM UT WOS:000232169200007 ER PT J AU Baker, SG Kramer, BS AF Baker, SG Kramer, BS TI Statistics for weighing benefits and harms in a proposed genetic substudy of a randomized cancer prevention trial SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE cancer prevention; case only; nested case-control; proportionate risk difference; risk difference; tamoxifen ID SURGICAL ADJUVANT BREAST; TAMOXIFEN AB When evaluating potential interventions for cancer prevention, it is necessary to compare benefits and harms. With new study designs, new statistical approaches may be needed to facilitate this comparison. A case in point arose in a proposed genetic substudy of a randomized trial of tamoxifen versus placebo in asymptomatic women who were at high risk for breast cancer. Although the randomized trial showed that tamoxifen substantially reduced the risk of breast cancer, the harms from tamoxifen were serious and some were life threaten-ing. In hopes of finding a subset of women with inherited risk genes who derive greater bene-fits from tamoxifen, we proposed a nested case-control study to test some trial subjects for various genes and new statistical methods to extrapolate benefits and harms to the general population. An important design question is whether or not the study should target common low penetrance genes. Our calculations show that useful results are only likely with rare high penetrance genes. C1 NCI, Biometry Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, NIH, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 7 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2005 VL 54 BP 941 EP 954 DI 10.1111/j.1467-9876.2005.00522.x PN 5 PG 14 WC Statistics & Probability SC Mathematics GA 968NM UT WOS:000232169200008 ER PT J AU Yordanov, AT Mollov, N Lodder, AL Woller, E Cloninger, M Walbridge, S Milenic, D Brechbiel, MW AF Yordanov, AT Mollov, N Lodder, AL Woller, E Cloninger, M Walbridge, S Milenic, D Brechbiel, MW TI A water-soluble triiodo amino acid and its dendrimer conjugate for computerized tomography (CT) imaging SO JOURNAL OF THE SERBIAN CHEMICAL SOCIETY LA English DT Article DE imaging; computed tomography; macromolecule; dendrimer; iodine ID CONTRAST AGENTS; POLYETHYLENE-GLYCOL; LABELED DENDRIMERS AB Prolonging the circulation of all an agent is vital for making it suitable for blood pool (vascular) imaging. Medical applications of vascular imaging include cardiovascular disease, abnormal capillary permeability, and tumor neovascularity. As low molecular weight computerized tomography (CT) enhancement agents are characterized by inconveniently fast clearance, macromolecular compounds (both natural and synthetic) have gained a wide recongnition for possessing better characteristics for performing blood imaging, tasks. Herein, the syntheses and characterization of a new water-soluble triiodo amino acid, 3-[(N,N-dimethylaminoacetyl)amino]-alpha-ethyl-2,4,6-triiodobenzenepropanoic acid (DMAA-IPA) and its Starburst PAMAM generation 4.0 dendrimer conjugate, G-4-(DMAA-IPA)(37) are described. The applicability of G-4-(DN4AA-IPA)(37) as a potential macromolecular angiographic CT contrast agent is discussed. The linear relationship between organically bound iodine concentration and CT Hounsfield units has been established thus allowing for quantification uses of CT imaging as well. C1 NINDS, Radioimmuno & Inorgan Chem Sect, Radiat Oncol Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Wyatt Technol Corp, Goleta, CA 93117 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. RP Yordanov, AT (reprint author), NINDS, Radioimmuno & Inorgan Chem Sect, Radiat Oncol Branch, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. EM ayordanov@easternisotopes.com NR 24 TC 9 Z9 10 U1 1 U2 9 PU SERBIAN CHEMICAL SOC PI BELGRADE PA KARNEGIJEVA 4, PO BOX 462, YU-11001 BELGRADE, YUGOSLAVIA SN 0352-5139 J9 J SERB CHEM SOC JI J. Serb. Chem. Soc. PY 2005 VL 70 IS 2 BP 163 EP 170 DI 10.2298/JSC0502163Y PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 912IW UT WOS:000228072300003 ER PT J AU Maxhimer, JB Reddy, RM Zuo, JT Cole, GW Schrump, DS Nguyen, DM AF Maxhimer, JB Reddy, RM Zuo, JT Cole, GW Schrump, DS Nguyen, DM TI Induction of apoptosis of lung and esophageal cancer cells treated with the combination of histone deacetylase inhibitor (trichostatin A) and protein kinase C inhibitor (calphostin C) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 25-MAY 28, 2004 CL Toronto, CANADA SP Amer Assoc Throac Surg ID DEPSIPEPTIDE-MEDIATED APOPTOSIS; NF-KAPPA-B; SP1 SITES; ACTIVATION; TRANSCRIPTION; FLAVOPIRIDOL; EXPRESSION; PATHWAY; P53 AB Objective: Histone deacetylase inhibitors mediate a potent growth-inhibitory effect in cancer cells through induction of cell-cycle arrest and apoptosis. Moreover, these agents significantly induce transcriptional activation of nuclear factor kappaB, as well as p21 regulated by protein kinase C, and are thought to negatively influence the ability of histone deacetylase inhibitor to effectively mediate apoptosis. This study aimed to evaluate the effect of calphostin C (a protein kinase C inhibitor) on trichostatin A (a histone deacetylase inhibitor)-mediated upregulation of nuclear factor kappaB and p21 promotor transcriptional activity, as well as induction of apoptosis in lung and esophageal cancer cells. Methods: Cultured lung and esophageal cancer cells were treated with calphostin C and trichostatin A. Nuclear factor kappaB transcriptional activity was quantitated by using the nuclear factor kappaB-luciferase assay. Transcription of p2l gene and p21 protein levels was evaluated by using the p21 promoter-luciferase assay and the p21 enzyme-linked immunoassay, respectively. Apoptosis was evaluated by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-based ApoBrdU assay. Levels of expression of nuclear factor kappaB-dependent antiapoptotic and proapoptotic proteins were evaluated by means of Western blotting. Results: Exposure of lung or esophageal cancer cells to trichostatin A resulted in a dose- and cell-dependent 2-fold to greater than 20-fold increase of nuclear factor kappaB and p21 transcriptional activity. Treatment with trichostatin A and calphostin C led to a 50% to 90% decrease of trichostatin A- mediated upregulation of nuclear factor kappaB and p21 activation. Inhibition of nuclear factor kappaB activity resulted in significant reduction (30% to >99%) of trichostatin A- mediated activation of not only nuclear factor kappaB transcription but also p21 promotor activity. Importantly, 90% to 96% of thoracic cancer cells under-went apoptosis after exposure to the combination of trichostatin A plus calphostin C. Conclusion: Inhibition of protein kinase C abrogates trichostatin A-mediated upregulation of nuclear factor kappaB transcriptional activity and p21 expression that is associated with profound induction of apoptosis in lung or esophageal cancer cells. Protein kinase C might be a novel target for enhancing the efficacy of histone deacetylase inhibitor in cancer therapy. C1 NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Natl Inst Hlth Res Scholar Program, Bethesda, MD 20817 USA. RP Nguyen, DM (reprint author), NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bldg 10,Room 2B07,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. EM Dao_Nguyen@nih.gov NR 20 TC 15 Z9 17 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 2005 VL 129 IS 1 BP 53 EP 63 DI 10.1016/j.jtcvs.2004.07.051 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 886HD UT WOS:000226216600009 PM 15632825 ER PT J AU Caudell, D Confer, AW Fulton, RW Berry, A Saliki, JT Fent, GM Ritchey, JW AF Caudell, D Confer, AW Fulton, RW Berry, A Saliki, JT Fent, GM Ritchey, JW TI Diagnosis of infectious canine hepatitis virus (CAV-1) infection in puppies with encephalopathy SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article AB Nine weaned Labrador Retriever puppies from a litter of 11 were presented with signs of acute central nervous system (CNS) disease that included ataxia and blindness. All puppies died. Gross examination of tissues from 2 puppies revealed regionally diffuse hemorrhages in the brain stem and swollen hemorrhagic lymph nodes. Light microscopic examination of hematoxylin and eosin-stained tissues showed numerous large, basophilic intranuclear inclusion bodies within CNS vascular endothelium and occasionally in individual hepatocytes. Immunohistochemical staining of the tissue was positive using an antibody against canine adenovirus-1. Virus isolation for infectious canine hepatitis virus was achieved using inoculated cell cultures. Polymerase chain reaction amplification of DNA from cell culture material revealed shared homology with other mammalian adenoviruses. C1 Oklahoma State Univ, Dept Vet Pathol, Stillwater, OK 74078 USA. Oklahoma State Univ, Oklahoma Anim Dis Diagnost Lab, Stillwater, OK 74078 USA. Isl Vet Serv, Kodiak, AK 99615 USA. RP Caudell, D (reprint author), USN, NCI, NIH, Ctr Med, Navy 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 8 TC 12 Z9 13 U1 0 U2 3 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD JAN PY 2005 VL 17 IS 1 BP 58 EP 61 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 888BG UT WOS:000226348600009 PM 15690952 ER PT J AU Chen, Y Wei, H Gao, B Hu, Z Zheng, S Tian, Z AF Chen, Y Wei, H Gao, B Hu, Z Zheng, S Tian, Z TI Activation and function of hepatic NK cells in hepatitis B infection: an underinvestigated innate immune response SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis B virus; innate immunity; natural killer cells ID NATURAL-KILLER-CELLS; CYTOTOXIC T-CELLS; VIRUS TRANSGENIC MICE; IN-VIVO; DENDRITIC CELLS; VIRAL-INFECTION; SURFACE-ANTIGEN; X-PROTEIN; HEPATOCELLULAR-CARCINOMA; ANTIVIRAL ACTIVITY AB Natural killer (NK) cells are abundant in the normal liver, accounting for around one-third of intrahepatic lymphocytes and are important in the defence against hepatitis B virus (HBV) infection as innate immune responses. In this review, we discuss the mechanisms of hepatic NK cell activity against HBV. Whether directly activated by HBV infection or indirectly activated by other lymphocytes such as NKT cells or antigen-presenting cells (APCs), hepatic NK cells exert their anti-viral functions by natural cytotoxicity and production of high levels of cytokines. However, activated NK cells play an important role in regulating adaptive immune responses by interaction with other lymphocytes such as T, B and APCs. In addition, NK cells may contribute to the lymphocyte-mediated liver injury during HBV infection that was previously considered to be mediated only by CD8+ T cells or/and NKT cells. C1 Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD USA. Showa Univ, Sch Med, Dept Microbiol & Immunol, Tokyo 142, Japan. Zhejiang Univ, Affiliated Hosp 1, Hangzhou 310027, Zhejiang, Peoples R China. RP Tian, Z (reprint author), Univ Sci & Technol China, Sch Life Sci, 443 Huangshan Rd, Hefei 230027, Anhui, Peoples R China. EM ustctzg@yahoo.com.cn RI Tian, Zhigang/J-3512-2013 NR 67 TC 48 Z9 56 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JAN PY 2005 VL 12 IS 1 BP 38 EP 45 DI 10.1111/j.1365-2893.2005.00543.x PG 8 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 889QR UT WOS:000226458000006 PM 15655046 ER PT J AU Hoshino, Y Dalai, SK Wang, K Pesnicak, L Lau, TY Knipe, DM Cohen, JI Straus, SE AF Hoshino, Y Dalai, SK Wang, K Pesnicak, L Lau, TY Knipe, DM Cohen, JI Straus, SE TI Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; RECURRENT GENITAL HERPES; CD8(+) T-CELLS; SPONTANEOUS REACTIVATION; IMMUNE-RESPONSES; TYPE-2; PROTECTION; HSV-2; VACCINATION; LATENCY AB Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. d15-29 was also effective in treating established infections. Moreover, latent d15-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8(+) T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the d15-29 vaccine may be a good candidate for early-phase human trials. C1 NIAID, Med Virol Sect, LCID, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Straus, SE (reprint author), NIAID, Med Virol Sect, LCID, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM strauss@mail.nih.gov FU NIAID NIH HHS [R01 AI057552, R56 AI057552, AI057552, 1-R43AI047510-01] NR 39 TC 76 Z9 82 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 1 BP 410 EP 418 DI 10.1128/JVI.79.1.410-418.2005 PG 9 WC Virology SC Virology GA 881YF UT WOS:000225904700038 PM 15596834 ER PT J AU Mbisa, JL Nikolenko, GN Pathak, VK AF Mbisa, JL Nikolenko, GN Pathak, VK TI Mutations in the RNase H primer grip domain of murine leukemia virus reverse transcriptase decrease efficiency and accuracy of plus-strand DNA transfer SO JOURNAL OF VIROLOGY LA English DT Article ID FREQUENT DUAL INITIATION; IN-VIVO ASSAY; RETROVIRAL REPLICATION; CRYSTAL-STRUCTURE; GENETIC-VARIATION; STRUCTURAL DETERMINANTS; DRUG-RESISTANCE; BINDING SITES; TYPE-1; HIV AB The RNase H primer grip of human immunodeficiency virus type 1 (HTV-1) reverse transcriptase (RT) contacts the DNA primer strand and positions the template strand near the RNase H active site, influencing RNase H cleavage efficiency and specificity. Sequence alignments show that 6 of the 11 residues that constitute the RNase H primer grip have functional equivalents in murine leukemia virus (MLV) RT. We previously showed that a Y586F substitution in the MLV RNase H primer grip resulted in a 17-fold increase in substitutions within 18 nucleotides of adenine-thymine tracts, which are associated with a bent DNA conformation. To further determine the effects of the MLV RNase H primer grip on replication fidelity and viral replication, we performed additional mutational analysis. Using either P-galactosidase (lacZ) or green fluorescent protein (GFP) reporter genes, we found that S557A, A558V, and Q559L substitutions resulted in statistically significant increases in viral mutation rates, ranging from 2.1- to 3.8-fold. DNA sequencing analysis of nonfluorescent GFP clones indicated that the mutations in RNase H primer grip significantly increased the frequency of deletions between the primer-binding site (PBS) and sequences downstream of the PBS. In addition, quantitative real-time PCR analysis of reverse transcription products revealed that the mutant RTs were substantially inefficient in plus-strand DNA transfer relative to the wild-type control. These results indicate that the MLV RNase H primer grip is an important determinant of in vivo fidelity of DNA synthesis and suggest that the mutant RT was unable to copy through the DNA-RNA junction of the minus-strand DNA and the tRNA because of its bent conformation resulting in error-prone plus-strand DNA transfer. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Rm 334, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov NR 44 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 1 BP 419 EP 427 DI 10.1028/JVI.79.1.419-427.2005 PG 9 WC Virology SC Virology GA 881YF UT WOS:000225904700039 PM 15596835 ER PT J AU Roberts, A Vogel, L Guarner, J Hayes, N Murphy, B Zaki, S Subbarao, K AF Roberts, A Vogel, L Guarner, J Hayes, N Murphy, B Zaki, S Subbarao, K TI Severe acute respiratory syndrome coronavirus infection of Golden Syrian hamsters SO JOURNAL OF VIROLOGY LA English DT Article ID PARAINFLUENZA VIRUS TYPE-3; SARS CORONAVIRUS; MUCOSAL IMMUNIZATION; AFRICAN-GREEN; MONKEYS; PROTEIN; REPLICATION; INFLUENZA; SINGAPORE; VACCINE AB Small animal models are needed in order to evaluate the efficacy of candidate vaccines and antivirals directed against the severe acute respiratory syndrome coronavirus (SARS CoV). We investigated the ability of SARS CoV to infect 5-week-old Golden Syrian hamsters. When administered intranasally, SARS CoV replicates to high titers in the lungs and nasal turbinates. Peak replication in the lower respiratory tract was noted on day 2 postinfection (p.i.) and was cleared by day 7 p.i. Low levels of virus were present in the nasal turbinates of a few hamsters at 14 days p.i. Viral replication in epithelial cells of the respiratory tract was accompanied by cellular necrosis early in infection, followed by an inflammatory response coincident with viral clearance, focal consolidation in pulmonary tissue, and eventual pulmonary tissue repair. Despite high levels of virus replication and associated pathology in the respiratory tract, the hamsters showed no evidence of disease. Neutralizing antibodies were detected in sera at day 7 p.i., and mean titers at day 28 p.i. exceeded 1:400. Hamsters challenged with SARS CoV at day 28 p.i. were completely protected from virus replication and accompanying pathology in the respiratory tract. Comparing these data to the mouse model, SARS CoV replicates to a higher titer and for a longer duration in the respiratory tract of hamsters and is accompanied by significant pathology that is absent in mice. Viremia and extrapulmonary spread of SARS CoV to liver and spleen, which are seen in hamsters, were not detected in mice. The hamster, therefore, is superior to the mouse as a model for the evaluation of antiviral agents and candidate vaccines against SARS CoV replication. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Ctr Dis Control, Natl Ctr Infect Dis, Infect Dis Pathol Activ, Atlanta, GA 30333 USA. RP Roberts, A (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6513,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM ajroberts@niaid.nih.gov RI Guarner, Jeannette/B-8273-2013 NR 27 TC 101 Z9 110 U1 3 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 1 BP 503 EP 511 DI 10.1128/JVI.79.1.503-511.2005 PG 9 WC Virology SC Virology GA 881YF UT WOS:000225904700047 PM 15596843 ER PT J AU Sullivan, NJ Peterson, M Yang, ZY Kong, WP Duckers, H Nabel, E Nabel, GJ AF Sullivan, NJ Peterson, M Yang, ZY Kong, WP Duckers, H Nabel, E Nabel, GJ TI Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway SO JOURNAL OF VIROLOGY LA English DT Article ID KAPOSIS-SARCOMA; IN-VITRO; IDENTIFICATION; CYTOTOXICITY; ENDOCYTOSIS; DNA AB Ebola virus infection causes a highly lethal hemorrhagic fever syndrome associated with profound immunosuppression through its ability to induce widespread inflammation and cellular damage. Though GP, the viral envelope glycoprotein, mediates many of these effects, the molecular events that underlie Ebola virus cytopathicity are poorly understood. Here, we define a cellular mechanism responsible for Ebola virus GP cytotoxicity. GP selectively decreased the expression of cell surface molecules that are essential for cell adhesion and immune function. GP dramatically reduced levels of alphaVbeta3 without affecting the levels of alpha2beta1 or cadherin, leading to cell detachment and death. This effect was inhibited in vitro and in vivo by brefeldin A and was dependent on dynamin, the GTPase. GP also decreased cell surface expression of major histocompatibility complex class I molecules, which alters recognition by immune cells, and this effect was also dependent on the mucin domain previously implicated in GP cytotoxicity. By altering the trafficking of select cellular proteins, Ebola virus GP inflicts cell damage and may facilitate immune escape by the virus. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20814 USA. NHLBI, NIH, Bethesda, MD USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3005, Bethesda, MD 20814 USA. EM gnabel@nih.gov NR 19 TC 53 Z9 61 U1 1 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 1 BP 547 EP 553 DI 10.1128/JVI.79.1.547-553.2005 PG 7 WC Virology SC Virology GA 881YF UT WOS:000225904700051 PM 15596847 ER PT J AU Akahata, W Yang, ZY Nabel, GJ AF Akahata, W Yang, ZY Nabel, GJ TI Comparative immunogenicity of human immunodeficiency virus particles and corresponding polypeptides in a DNA vaccine SO JOURNAL OF VIROLOGY LA English DT Article ID GENETIC IMMUNIZATION; ATTENUATED SIV; TYPE-1; MACAQUES; INFECTION; GLYCOPROTEIN; RESPONSES; ENVELOPE; PROTEIN; LIVE AB The immunogenicity of a plasmid DNA expression vector encoding both Gag and envelope (Env), which produced human immunodeficiency virus (HIV) type 1 virus-like particles (VLP), was compared to vectors expressing Gag and Env individually, which presented the same gene products as polypeptides. Vaccination with plasmids that generated VLP showed cellular immunity comparable to that of Gag and cell-mediated or humoral responses similar to those of Env as immunization with separate vectors. These data suggest that DNA vaccines encoding separated HIV polypeptides generate immune responses similar to those generated by viral particles. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 25 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 1 BP 626 EP 631 DI 10.1128/JVI.79.1.626-631.2005 PG 6 WC Virology SC Virology GA 881YF UT WOS:000225904700062 PM 15596858 ER PT J AU Mascola, JR Sambor, A Beaudry, K Santra, S Welcher, B Louder, MK VanCott, TC Huang, Y Chakrabarti, BK Kong, WP Yang, ZY Xu, L Montefiori, DC Nabel, GJ Letvin, NL AF Mascola, JR Sambor, A Beaudry, K Santra, S Welcher, B Louder, MK VanCott, TC Huang, Y Chakrabarti, BK Kong, WP Yang, ZY Xu, L Montefiori, DC Nabel, GJ Letvin, NL TI Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins SO JOURNAL OF VIROLOGY LA English DT Article ID GENETIC IMMUNIZATION; VACCINIA VIRUS; RHESUS-MONKEYS; PROTECTIVE EFFICACY; MUCOSAL CHALLENGE; AIDS VACCINE; GAG GENE; IMMUNOGENICITY; ENVELOPE; MACAQUES AB Immunization with recombinant serotype 5 adenoviral (rAd5) vectors or a combination of DNA plasmid priming and rAd5 boosting is known to elicit potent immune responses. However, little data exist regarding these immunization strategies and the development of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. We used DNA plasmids and rAd5 vectors encoding the HIV-1 89.6P or chimeric HxB2/BaL envelope glycoprotein to immunize macaque monkeys. A single rAd5 immunization elicited anti-Env antibody responses, but there was little boosting with subsequent rAd5 immunizations. In contrast, rAd5 boosting of DNA-primed monkeys resulted in a rapid rise in antibody titers, including the development of anti-HIV-1 neutralizing antibodies. The potency and breadth of neutralization were evaluated by testing plasma against a panel of 14 clade B primary isolates. Moderate levels of plasma neutralizing activity were detected against about one-third of the viruses tested, and immunoglobulin G fractionation demonstrated that virus neutralization was antibody mediated. After a challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P), an anamnestic neutralizing antibody response was observed, although the breadth of the response was limited to the subset of viruses that were neutralized after the primary immunization. These data are the first detailed description of the anti-HIV-1 neutralizing antibody response in nonhuman primates elicited by DNA and rAd5 immunization. In addition to the well-established ability of DNA priming and rAd5 boosting to elicit potent anti-HIV-1 cellular immune responses, this immunization strategy elicits anti-HfV-1 neutralizing antibodies and therefore can be used to study novel Env immunogens designed to elicit more potent neutralizing antibodies. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Rockville, MD USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM jmascola@nih.gov NR 31 TC 84 Z9 88 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 2 BP 771 EP 779 DI 10.1128/JVI.79.2.771-779.2005 PG 9 WC Virology SC Virology GA 885IG UT WOS:000226149700012 PM 15613305 ER PT J AU Graff, J Nguyen, H Kasorndorkbua, C Halbur, PG St Claire, M Purcell, RH Emerson, SU AF Graff, J Nguyen, H Kasorndorkbua, C Halbur, PG St Claire, M Purcell, RH Emerson, SU TI In vitro and in vivo mutational analysis of the 3 '-terminal regions of hepatitis E virus genomes and replicons SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT RNA-POLYMERASE; ORF3 PROTEIN; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MOLECULAR-CLONING; CAPSID PROTEIN; SWINE HEV; IDENTIFICATION; INFECTION; BINDS; HETEROGENEITY AB Hepatitis E virus (HEV) replication is not well understood, mainly because the virus does not infect cultured cells efficiently. However, Huh-7 cells transfected with full-length genomes produce open reading frame 2 protein, indicative of genome replication (6). To investigate the role of Y-terminal sequences in RNA replication, we constructed chimeric full-length genomes with divergent Y-terminal sequences of genotypes 2 and 3 replacing that of genotype I and transfected them into Huh-7 cells. The production of viral proteins by these full-length chimeras was indistinguishable from that of the wild type, suggesting that replication was not impaired. In order to better quantify HEV replication in cell culture, we constructed an HEV replicon with a reporter (luciferase). Luciferase production was cap dependent and RNA-dependent RNA polymerase dependent and increased following transfection of Huh-7 cells. Replicons harboring the Y-terminal intergenotypic chimera sequences were also assayed for luciferase production. In spite of the large sequence differences among the 3' termini of the viruses, replication of the chimeric replicons was surprisingly similar to that of the parental replicon. However, a single unique nucleotide change within a predicted stem structure at the 3' terminus substantially reduced the efficiency of replication: RNA replication was partially restored by a covariant mutation. Similar patterns of replication were obtained when full-length genomes were inoculated into rhesus macaques, suggesting that the in vitro system could be used to predict the effect of Y-terminal mutations in vivo. Incorporation of the Y-terminal sequences of the swine strain of HEV into the genotype I human strain did not enable the human strain to infect swine. C1 NIAID, Mol Hepatitis Sect, LID, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, LID, NIH, Bethesda, MD 20892 USA. Iowa State Univ, Coll Vet Med, Dept Vet Diagnost & Prod Anim Med, Ames, IA USA. Bioqual Inc, Rockville, MD USA. RP Graff, J (reprint author), NIAID, Mol Hepatitis Sect, LID, NIH, Bldg 50,Room 6535,50 South Dr,MSC 8009, Bethesda, MD 20892 USA. EM jgraff@niaid.nih.gov FU PHS HHS [1-A0-02733] NR 46 TC 29 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 2 BP 1017 EP 1026 DI 10.1128/JVI.78.2.1017.1026.2005 PG 10 WC Virology SC Virology GA 885IG UT WOS:000226149700037 PM 15613330 ER PT J AU Zhang, LQ Bukreyev, A Thompson, CI Watson, B Peeples, ME Collins, PL Pickles, RJ AF Zhang, LQ Bukreyev, A Thompson, CI Watson, B Peeples, ME Collins, PL Pickles, RJ TI Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium SO JOURNAL OF VIROLOGY LA English DT Article ID HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEINS; HEPARAN-SULFATE GLYCOSAMINOGLYCANS; MEDIATED GENE-TRANSFER; PERICILIARY LIQUID; MEMBRANE-FUSION; APICAL SURFACE; TARGET-CELLS; LIPID RAFTS; RECEPTOR; REQUIREMENTS AB We constructed a human recombinant parainfluenza virus type 3 (rPIV3) that expresses enhanced green fluorescent protein (GFP) and used this virus, rgPIV3, to characterize PIV3 infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). The apical surface of RAE was highly susceptible to rgPIV3 infection, whereas only occasional cells were infected when virus was applied to the basolateral surface. Infection involved exclusively ciliated epithelial cells. There was little evidence of virus-mediated cytopathology and no spread of the virus beyond the ciliated cell types. Infection of ciliated cells by rgPIV3 was sensitive to a neuraminidase specific for alpha2-6-linked sialic acid residues, but not to a neuraminidase that cleaves alpha2-3- and alpha2-8-linked sialic acid residues. This provided evidence that rgPIV3 utilizes alpha2-6-linked sialic acid residues for initiating infection, a specificity also described for human influenza viruses. The PIV3 fusion (F) glycoprotein was trafficked exclusively to the apical surface of ciliated cells, which also was the site of release of progeny virus. F glycoprotein localized predominately to the membranes of the cilial shafts, suggesting that progeny viruses may bud from cilia per se. The polarized trafficking of F glycoprotein to the apical surface also likely restricts its interaction with neighboring cells and could account for the observed lack of cell-cell fusion. HAE derived from cystic fibrosis patients was not more susceptible to rgPIV3 infection but did exhibit limited spread of virus due to impaired movement of lumenal secretions due to compromised function of the cilia. C1 Univ N Carolina, CF Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. NIAID, Resp Viruses Sect, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus Childrens Res Inst, Ctr Vaccines & Immun, Columbus, OH 43210 USA. Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. RP Pickles, RJ (reprint author), Univ N Carolina, CF Pulm Res & Treatment Ctr, 7021 Thurston Bowles, Chapel Hill, NC 27599 USA. EM branston@med.unc.edu FU NHLBI NIH HHS [HL 51818-09, HL 66943-01, P01 HL051818] NR 53 TC 140 Z9 143 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 2 BP 1113 EP 1124 DI 10.1128/JVI.79.2.1113-1124.2005 PG 12 WC Virology SC Virology GA 885IG UT WOS:000226149700046 PM 15613339 ER PT J AU Zaragoza, C Li, RM Fahle, GA Fischer, SH Raffeld, M Lewis, AM Kopp, JB AF Zaragoza, C Li, RM Fahle, GA Fischer, SH Raffeld, M Lewis, AM Kopp, JB TI Squirrel monkeys support replication of BK virus more efficiently than simian virus 40: an animal model for human BK virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSPLANT RECIPIENTS; HUMAN PAPOVAVIRUS; RHESUS-MONKEYS; BRAIN TUMORS; JC-VIRUS; SV40; URINE; NEPHROPATHY; HAMSTERS; KIDNEYS AB We performed experiments to test the suitability of squirrel monkeys (Saimiri sciureus) as an experimental model for BK virus (BKV) and simian virus 40 (SV40) infection. Four squirrel monkeys received intravenous inoculation with BKV Gardner strain, and six squirrel monkeys received intravenous inoculation with SV40 777 strain. Eight of 10 monkeys received immunosuppression therapy, namely, cyclophosphamide subcutaneously either before or both before and after viral inoculation. The presence of viral infection was assessed by quantitative real-time PCR amplification of viral DNA from blood, urine, and 10 tissues. We found that squirrel monkeys were susceptible to infection with BKV, with high viral copy number detected in blood and viral genome detected in all tissues examined. BKV genome was detected in urine from only one monkey, while three monkeys manifested focal interstitial nephritis. BKV T antigen was expressed in renal peritubular capillary endothelial cells. By contrast, SV40 was detected at very low copy numbers in only a few tissues and was not detected in blood. We conclude that the squirrel monkey is a suitable animal for studies of experimental BKV infection and may facilitate studies of viral entry, pathogenesis, and therapy. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Dept Hlth & Human Serv, Bethesda, MD USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10-3N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 22 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 2 BP 1320 EP 1326 DI 10.1128/JVI.79.2.1320-1326.2005 PG 7 WC Virology SC Virology GA 885IG UT WOS:000226149700066 PM 15613359 ER PT J AU Read, JCA Cumming, BG AF Read, JCA Cumming, BG TI The stroboscopic Pulfrich effect is not evidence for the joint encoding of motion and depth SO JOURNAL OF VISION LA English DT Article DE binocular vision; interocular delay; Pulfrich effect; psychophysics; computational modeling ID DYNAMIC VISUAL NOISE; CORTICAL-NEURONS; BINOCULAR DELAY; PERCEPTION; DISPARITY; AREA; INTEGRATION; STEREOPSIS; MACAQUE; STEREOPHENOMENON AB In the Pulfrich effect, an illusion of depth is produced by introducing differences in the times at which a moving object is presented to the two eyes. In the classic form of the illusion, there is a simple explanation for the depth percept: the interocular delay introduces a spatial disparity into the stimulus. However, when the moving object is viewed stroboscopically, this simple explanation no longer holds. In recent years, depth perception in the stroboscopic Pulfrich effect has been explained by invoking neurons that are sensitive both to stereo disparity and to direction of motion. With such joint motion/disparity encoders, interocular delay causes a perception of depth by causing a shift in each neuron's preferred disparity. This model has been implemented by N. Qian and R. A. Andersen (1997). Here we show that this model's predictions for perceived disparity are quantitatively at odds with psychophysical measures. The joint-encoding model predicts that the perceived disparity is the virtual disparity implied by the apparent motion; in fact, the perceived disparity is smaller. We show that the percept can be quantitatively explained on the basis of spatial disparities present in the stimulus, which could be extracted from pure disparity sensors. These results suggest that joint encoding of motion and depth is not the dominant neuronal basis of depth perception in this stimulus. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Read, JCA (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM jcr@lsr.nei.nih.gov RI Read, Jenny/A-7493-2013 OI Read, Jenny/0000-0002-9029-5185 FU NEI NIH HHS [Z01 EY000404-04] NR 30 TC 15 Z9 15 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2005 VL 5 IS 5 BP 417 EP 434 DI 10.1167/5.5.3 PG 18 WC Ophthalmology SC Ophthalmology GA 933WQ UT WOS:000229664000003 PM 16097873 ER PT J AU Maier, A Logothetis, NK Leopold, DA AF Maier, A Logothetis, NK Leopold, DA TI Global competition dictates local suppression in pattern rivalry SO JOURNAL OF VISION LA English DT Article DE multistable perception; perceptual organization; monocular rivalry; visual suppression ID PRIMARY VISUAL-CORTEX; FIGURE-GROUND SEGREGATION; MOTION-INDUCED BLINDNESS; BINOCULAR-RIVALRY; MONOCULAR RIVALRY; SPATIAL-FREQUENCY; EYE-MOVEMENTS; NEURAL MECHANISM; HUMAN BRAIN; CONTOURS AB Certain pairs of visual patterns, when superimposed as if transparent, elicit a wavering percept in which one or the other pattern can enjoy temporary periods of exclusive visibility. This multistable perceptual phenomenon is called monocular rivalry or pattern rivalry ( PR) and is most pronounced when the component patterns are faint and devoid of detail. The principal mechanisms that give rise to PR continue to be a topic of speculation. In the present study, we examine the determinants of exclusive dominance during PR using a novel stimulus in which a central portion is free of conflict. By observing the properties of suppression in this so-called rivalry-free region, we demonstrate that perception is driven largely by the global and holistic interpretation of the patterns, rather than by the need to resolve local spatial conflict. The suppression of this central region was often complete and varied as a function of the parameters of the global stimulus, including the size of the surround region, its ocular configuration, and stereoscopic depth ordering. Suppression also varied as a function of pattern continuity across the central region as well as with the temporal offset of the overlapping components. These findings demonstrate that the visibility or invisibility of a pattern is not fundamentally a product of local processing, but is instead shaped by the brain's global interpretive assumptions regarding the composition of the stimulus. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. RP Leopold, DA (reprint author), NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov RI Maier, Alexander/B-7489-2009; OI Maier, Alexander/0000-0002-7250-502X; Leopold, David/0000-0002-1345-6360 NR 60 TC 18 Z9 18 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2005 VL 5 IS 9 BP 668 EP 677 DI 10.1167/5.9.2 PG 10 WC Ophthalmology SC Ophthalmology GA 993JC UT WOS:000233949400002 PM 16356077 ER PT J AU Read, JCA Cumming, BG AF Read, JCA Cumming, BG TI All Pulfrich-like illusions can be explained without joint encoding of motion and disparity SO JOURNAL OF VISION LA English DT Article DE binocular vision; computational modeling; interocular delay; primary visual cortex; Pulfrich effect; psychophysics ID DYNAMIC VISUAL NOISE; CORTICAL-NEURONS; BINOCULAR DISPARITY; STEREOSCOPIC DEPTH; APPARENT MOTION; V1 NEURONS; AREA MT; DIRECTION SELECTIVITY; INTEROCULAR DELAY; STRIATE CORTEX AB In the Pulfrich effect, an interocular time delay results in the perception of depth. Two modified versions, the stroboscopic Pulfrich effect and dynamic visual noise with a delay, are generally explained by postulating an early stage of space/time-inseparable filtering, encoding motion and disparity jointly. However, most disparity sensors in monkey V1 do not show joint motion/disparity encoding, and we recently showed that depth perception in the stroboscopic Pulfrich effect is equally compatible with space/time-separable filtering. Here, we demonstrate that this filtering can be implemented with a population of physiologically plausible energy model units. Similar results are obtained whether the neurons are pure disparity sensors ( like most V1 neurons) or joint motion/disparity sensors ( like MT). We also demonstrate that the dynamic noise stimulus produces correlations between the activity in pure disparity sensors, and in a separate population of pure motion sensors. These correlations are sufficient to explain the percept. Thus, joint encoding of motion and disparity is not required to explain depth perception in Pulfrich-like stimuli: a brain which encoded motion and disparity in entirely separate neuronal pathways could still experience all of these illusions. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Read, JCA (reprint author), Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM J.C.A.Read@ncl.ac.uk RI Read, Jenny/A-7493-2013 OI Read, Jenny/0000-0002-9029-5185 FU Intramural NIH HHS NR 49 TC 8 Z9 8 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2005 VL 5 IS 11 BP 901 EP 927 DI 10.1167/5.11.1 PG 27 WC Ophthalmology SC Ophthalmology GA 009XP UT WOS:000235147200001 PM 16441193 ER PT J AU Ferrucci, L AF Ferrucci, L TI An exciting thought SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID PHYSICAL-ACTIVITY; FRAIL; INFLAMMATION; DISABILITY C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21225 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, 3001 S Hanover St,NM540, Baltimore, MD 21225 USA. EM ferruccilu@mail.nih.gov NR 17 TC 5 Z9 5 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2005 VL 60 IS 1 BP 56 EP 56 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 902MF UT WOS:000227360500008 ER PT J AU Onder, G Penninx, BWJH Ferrucci, L Fried, LP Guralnik, JM Pahor, M AF Onder, G Penninx, BWJH Ferrucci, L Fried, LP Guralnik, JM Pahor, M TI Measures of physical performance and risk for progressive and catastrophic disability: Results from the women's health and aging study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DISABLED OLDER WOMEN; LOWER-BODY FUNCTION; SUBSEQUENT DISABILITY; PREDICTOR; AGE; VALIDATION; DIFFICULTY; STRENGTH; ABILITY; ADULTS AB Background. Physical performance measures can predict incident disability, but little research has assessed and compared how these measures predict progressive and rapid-onset (catastrophic) disability. The authors evaluated the ability of upper and lower extremity performance measures to predict progressive and catastrophic disability in activities of daily living (ADL), mobility, and upper extremity function. Methods. The incidence of progressive and catastrophic disability was assessed semiannually during a 3-year period in 884 women participating in the Women's Health and Aging Study I. Four-meter walking speed. balance, and chair stands tests were used to evaluate lower extremity function. The putting-on -blouse test. the Purdue pegboard test. and grip strength were used to assess upper extremity function. Summary performance scores (SPS) for the lower and upper extremities were calculated. Among participants in whom disability developed, those who reported no difficult in the previous year were defined as cases of catastrophic disability, and those who previously reported little or some difficulty were considered to be cases of progressive disability. Cox proportional hazard regression analyses were used to evaluate the association of performance measures and time to incident disability. The predictive ability of performance measures was compared using receiver-operator characteristic curves. Results. All lower and upper extremity measures. with the exception of grip strength. significantly predicted the onset of progressive ADL disability. but only walking speed was significantly associated with the onset of catastrophic ADL disability. The chair stands test. walking speed. and the lower extremity SPS were significantly associated with the onset of both progressive and catastrophic mobility disability. Only lower extremity individual tests and SPS significantly predicted the onset of both progressive and catastrophic upper extremity disability. The receiver-operator characteristic curves for ADL and mobility disability showed that all performance measures evaluated had a greater predictive ability for progressive than for catastrophic incident disability. This finding, was not consistent for upper extremity disability. The areas under the curve for walking speed and lower extremity SPS were very similar. ranging from 0.58 to 0.81 and front 0.57 to 0.85, and the predictive ability of these two measures was the greatest for all disability outcomes assessed. Conclusion. Physical performance measures of lower extremity and. in particular, walking speed and lower extremity SPS are valuable tools to predict different forms of disability. especially those with a progressive onset. C1 Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Policlin A Gemelli, Dept Geriatr, I-00168 Rome, Italy. Wake Forest Univ Hlth Sci, Sticht Ctr Aging, Winston Salem, NC USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD USA. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD USA. RP Onder, G (reprint author), Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Policlin A Gemelli, Dept Geriatr, L Francesco Vito 1, I-00168 Rome, Italy. FU NIA NIH HHS [1P30 AG 21332-01, N01AG12112] NR 34 TC 168 Z9 172 U1 2 U2 8 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2005 VL 60 IS 1 BP 74 EP 79 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 902MF UT WOS:000227360500011 PM 15741286 ER PT J AU Alscher, DM Braun, N Biegger, D Stuelten, C Gawronski, K Murdter, TE Kuhlmann, U Fritz, P AF Alscher, DM Braun, N Biegger, D Stuelten, C Gawronski, K Murdter, TE Kuhlmann, U Fritz, P TI Induction of metallothionein in proximal tubular cells by zinc and its potential as an endogenous antioxidant SO KIDNEY & BLOOD PRESSURE RESEARCH LA English DT Article DE metallothionein; zinc; kidney; tubular cells; reactive oxygen species ID RADIOCONTRAST-INDUCED NEPHROPATHY; N-ACETYLCYSTEINE; DIABETIC-NEPHROPATHY; OXIDATIVE STRESS; WILSONS-DISEASE; PROTEIN-KINASE; PREVENTION; GENERATION; GLOMERULI; INCREASES AB Background: This study was undertaken to gain further insights into the expression of metallothionein (MT) in kidney, to define the necessary dosage of a metal ( zinc) to achieve induction of MT and to evaluate the antioxidative potential of MT in comparison to other more common antioxidative therapeutics, like N-acetyl-L-cysteine (NAC), and endogenous molecules, like glutathione. Methods: MT was measured in renal specimens from cadaver kidneys from patients with chronic diseases (n = 76) and controls ( n = 21) by immunohistochemistry. In addition, induction experiments were performed in cell cultures of proximal tubular cells (LCC-PK1) and MT measured on the RNA and protein level ( immunohistochemistry, Western and dot blotting). Antioxidative potential of MT was compared to NAC and glutathione. Results: MT was restricted to tubular cells with no differences between controls and patients. Zn caused a dose-dependent increase of MT on the RNA as well as on the protein level (RNA (ratio MT/histone 3.3): control 0.34 &PLUSMN; 0.12; Zn 17 μ M 0.65 &PLUSMN; 0.26; Zn 35 μ M 1.25 &PLUSMN; 0.43 (p < 0.05), Zn 52 μ M 1.35 &PLUSMN; 0.46 (p < 0.05), and protein: 5.8-fold increase from 47 &PLUSMN; 13 mg/g total protein (n = 6) to 272 &PLUSMN; 140 mg/g total protein (n = 6)). The antioxidative effect of MT was equal to NAC and glutathione. Conclusions: Induction of renal MT by zinc is easily achievable and might be an interesting therapeutic and preventive tool against oxidative stress. Copyright (C) 2005 S. Karger AG, Basel. C1 Robert Bosch Krankenhaus, Dept Internal Med, Div Gen Internal Med & Nephrol, DE-70376 Stuttgart, Germany. Robert Bosch Krankenhaus, Dept Diagnost Med, Div Pathol, DE-70376 Stuttgart, Germany. Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Alscher, DM (reprint author), Robert Bosch Krankenhaus, Dept Internal Med, Div Gen Internal Med & Nephrol, Auerbachstr 10, DE-70376 Stuttgart, Germany. EM dominik.alscher@bk.de OI Alscher, Mark Dominik/0000-0002-9658-1211 NR 34 TC 21 Z9 22 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-4096 J9 KIDNEY BLOOD PRESS R JI Kidney Blood Pressure Res. PY 2005 VL 28 IS 3 BP 127 EP 133 DI 10.1159/000084921 PG 7 WC Physiology; Urology & Nephrology; Peripheral Vascular Disease SC Physiology; Urology & Nephrology; Cardiovascular System & Cardiology GA 932TJ UT WOS:000229576000001 PM 15812196 ER PT J AU Fox, CS Yang, Q Guo, CY Cupples, LA Wilson, PWF Levy, D Meigs, JB AF Fox, CS Yang, Q Guo, CY Cupples, LA Wilson, PWF Levy, D Meigs, JB TI Genome-wide linkage analysis to urinary microalbuminuria in a community-based sample: The Framingham Heart Study SO KIDNEY INTERNATIONAL LA English DT Article DE microalbuminuria; kidney; genetics; linkage ID ALBUMIN EXCRETION; DIABETIC-NEPHROPATHY; CARDIOVASCULAR MORTALITY; VARIANCE-COMPONENTS; RENAL-INSUFFICIENCY; CHROMOSOME 19Q13; BLOOD-PRESSURE; DISEASE; PREDICTOR; PEDIGREES AB Introduction. Microalbuminuria is a powerful risk factor for cardiovascular disease. It is not known whether genetic factors play a role in the expression of microalbuminuria in population-based samples. Methods. Genome-wide variance components linkage-analysis using 401 markers spaced at similar to10 cM was performed on subjects from 330 extended families of the Framingham Heart Study; a subanalysis was performed on families enriched for hypertension. Urinary microalbumin was indexed to urinary creatinine [urine albumin/creatinine ratio (UACR)] and was log-transformed for analysis. Residuals of log-transformed UACR adjusted for age, gender, body mass index, diabetes, systolic blood pressure, hypertension treatment, smoking, and serum creatinine were used in the linkage analysis. Results. Among 1055 subjects (52% women), mean age 56 years, median UACR was 5.8 mg/g (11%>30 mg/g). The unadjusted heritability for UACR was 0.20; after multivariable adjustment, heritability was 0.16. The peak multivariable-adjusted multipoint logarithm of odds (LOD) score was 2.22 on chromosome 8 at 135 cM (marker D8S1179); one LOD support interval=129-145 cM. In the subanalysis in families enriched for hypertension (N=676), the peak multivariable-adjusted LOD score of 2.11 was observed at the same location. Conclusion. We found suggestive linkage to urinary microalbumin on chromosome 8. At least one potential candidate gene implicated in the pathogenesis of nephropathy (HAS2) lies in this region. Further research is warranted to understand the genetic basis of microalbuminuria. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014 FU NHLBI NIH HHS [N01-HC-25195] NR 36 TC 37 Z9 38 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2005 VL 67 IS 1 BP 70 EP 74 DI 10.1111/j.1523-1755.2005.00056.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 878GO UT WOS:000225635000007 PM 15610229 ER PT S AU Post, RM Zhang, ZJ Weiss, SRB Xing, G Obeng, K AF Post, R. M. Zhang, Z-J Weiss, S. R. B. Xing, G. Obeng, K. BE Corcoran, ME Moshe, SL TI Contingent tolerance and cross tolerance to anticonvulsant effects in amygdala-kindled seizures: Mechanistic and clinical implications SO Kindling 6 SE ADVANCES IN BEHAVIORAL BIOLOGY LA English DT Proceedings Paper CT 6th International Conference on Kindling CY JUN 04-06, 2004 CL Victoria, CANADA SP UCB Pharma, Ortho McNeil, Glaxco Welcom, Novartis, Pfizer, Univ Saskatchewan, Albert Einstein Coll Med, Montefiore Med Ctr ID ANTIEPILEPTIC DRUG LEVETIRACETAM; TERM FOLLOW-UP; TRIGEMINAL NEURALGIA; ELECTRICAL STIMULATION; AFFECTIVE-DISORDERS; AFFECTIVE-ILLNESS; BIPOLAR DISORDER; CARBAMAZEPINE; RATS; LAMOTRIGINE C1 NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NR 42 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0099-9962 BN 0-387-24380-1 J9 ADV BEHAV BIOL PY 2005 VL 55 BP 305 EP 314 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA BEG99 UT WOS:000237245700029 ER PT J AU Bartlett, DH AF Bartlett, DH TI Aquatic facility design - Designing for Atlantis SO LAB ANIMAL LA English DT Review AB The requirements for aquatic facility design differ greatly from those of a rodent facility. The author discusses factors to consider when planning new construction of an aquatic facility or renovating space to house aquatic species. C1 NICHHD, Lab Anim & Fisheries Facil, NIH, Bethesda, MD 20892 USA. RP Bartlett, DH (reprint author), NICHHD, Lab Anim & Fisheries Facil, NIH, Bethesda, MD 20892 USA. EM db148n@nih.gov NR 17 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2005 VL 34 IS 1 BP 39 EP 45 DI 10.1038/laban0105-39 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 885VU UT WOS:000226186100008 PM 19795591 ER PT J AU Ning, EMLL Ronchetti, R Torres-Cabala, CA Teller, LS Merino, MJ AF Ning, EMLL Ronchetti, R Torres-Cabala, CA Teller, LS Merino, MJ TI Chromogenic in situ hybridization (CISH), a helpful tool for the pathologist to identify HER2/NEU amplification in breast carcinomas. Comparative study with IHC and FISH SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 173 BP 40A EP 40A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600174 ER PT J AU Atkins, KA Jeronimo, J Stoler, M AF Atkins, KA Jeronimo, J Stoler, M CA ALTS Trial TI Women with squamous cell carcinoma but mildly abnormal cytology: Review of the ALTS trial cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Virginia, Charlottesville, VA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 265 BP 60A EP 60A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600266 ER PT J AU Fetsch, PA Abati, A AF Fetsch, PA Abati, A TI HER2 immunostaining in cytologic samples of metastatic breast cancer: Does antibody clone and pretreatment method effect results? SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 287 BP 65A EP 65A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600288 ER PT J AU Maygarden, SJ Funkhouser, W Flake, G Slebos, R Detterbeck, F Taylor, J Rivera, M AF Maygarden, SJ Funkhouser, W Flake, G Slebos, R Detterbeck, F Taylor, J Rivera, M TI Comparison of biopsy and cytology samples taken with the light induced fluorescence endoscopy (LIFE) bronchoscopy system SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 UNC, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC USA. Vanderbilt Univ Sch Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 320 BP 72A EP 72A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600321 ER PT J AU Schinstine, M Filie, A Wilson, W Stetler-Stevenson, M Abati, A AF Schinstine, M Filie, A Wilson, W Stetler-Stevenson, M Abati, A TI Subsequent detection of lymphoid malignancy in cerebrospinal fluid (CSF) previously diagnosed as atypical or suspicious SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 340 BP 76A EP 76A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600341 ER PT J AU Aisner, DL Rosenberg, SA Berman, DM AF Aisner, DL Rosenberg, SA Berman, DM TI Loss of S100 immunoreactivity in metastatic melanoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 367 BP 82A EP 82A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600368 ER PT J AU Berman, DM Wincovitch, S Garfield, S Romeo, MJ AF Berman, DM Wincovitch, S Garfield, S Romeo, MJ TI Three-dimensional modeling of pigmented lesions can distinguish between benign and malignant melanocytes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 369 BP 82A EP 82A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600370 ER PT J AU Hartmann, DP Kallakury, B Luka, J Appella, EA Owor, G Jones, DM Sheehan, CE Azumi, N Ross, JS AF Hartmann, DP Kallakury, B Luka, J Appella, EA Owor, G Jones, DM Sheehan, CE Azumi, N Ross, JS TI Immunohistochemical expression of the PPM1D/wip-1 protein correlates with aggressive tumor behavior in invasive colorectal carinomas (CRCS) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Georgetown Univ Hosp, Washington, DC 20007 USA. Trevigen Inc, Gaithersburg, MD USA. NIH, GRS, Bethesda, MD 20892 USA. Albany Med Coll, Albany, NY 12208 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 479 BP 105A EP 106A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600480 ER PT J AU De Marzo, AM Platz, EA Epstein, JI Billis, A Chan, TY Cheng, L Datta, M Ertoy-Baydar, D Farre, X Fine, S Iczkowski, KA Ittmann, M Knudsen, BS Loda, M Lopez-Beltran, A Magi-Galluzzi, C Mikuz, G Montironi, R Rubin, MA Sebo, T Sesterhenn, IA Shah, R Signoretti, S Simko, J Troncoso, P Tsuzuki, T van Leenders, GJLH Yang, X Zhou, M Figg, WD Hoque, A Lucia, MS AF De Marzo, AM Platz, EA Epstein, JI Billis, A Chan, TY Cheng, L Datta, M Ertoy-Baydar, D Farre, X Fine, S Iczkowski, KA Ittmann, M Knudsen, BS Loda, M Lopez-Beltran, A Magi-Galluzzi, C Mikuz, G Montironi, R Rubin, MA Sebo, T Sesterhenn, IA Shah, R Signoretti, S Simko, J Troncoso, P Tsuzuki, T van Leenders, GJLH Yang, X Zhou, M Figg, WD Hoque, A Lucia, MS TI Interobserver reproducibility of a proposed classification of focal prostate atrophy lesions SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Colorado, Boulder, CO 80309 USA. Univ Campinas, Campinas, SP, Brazil. Emory Univ, Atlanta, GA 30322 USA. VA Med Ctr, Gainesville, FL USA. Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cordoba, E-14071 Cordoba, Spain. Cleveland Clin, Cleveland, OH USA. Innsbruck Med Univ, Innsbruck, Austria. Poltech U Som, Ancona, Italy. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Evanston, IL 60208 USA. NIH, Bethesda, MD 20892 USA. Indiana Univ, Bloomington, IN 47405 USA. RI Billis, Athanase/D-7365-2012; BAYDAR, DILEK/I-9610-2013; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 622 BP 135A EP 135A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600623 ER PT J AU Deas-Wooten, KD Herrmann, P Torres-Cabala, CA Linehan, MW Merino, MJ AF Deas-Wooten, KD Herrmann, P Torres-Cabala, CA Linehan, MW Merino, MJ TI Expression of oxidative complex enzymes assist in the differential diagnosis of renal tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 624 BP 136A EP 136A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600625 ER PT J AU Dhir, R Datta, MW Melamed, J Becich, MJ Bosland, MC Kajdacsy-Balla, AA Orenstein, J Silver, S Berman, J AF Dhir, R Datta, MW Melamed, J Becich, MJ Bosland, MC Kajdacsy-Balla, AA Orenstein, J Silver, S Berman, J TI Changes in tumor and HGPIN characteristics in radical prostatectomy specimens from 1990 to 2004: Results from the NCI cooperative prostate cancer tissue resource (CPCTR) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. NYU, New York, NY USA. Univ Illinois, Chicago, IL USA. George Washington Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 626 BP 136A EP 136A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600627 ER PT J AU Torres-Cabala, C Ning, EML Palau, MA Zbar, B Linehan, WM Merino, MJ AF Torres-Cabala, C Ning, EML Palau, MA Zbar, B Linehan, WM Merino, MJ TI Expression of KIT in hereditary renal cell carcinoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 772 BP 167A EP 167A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238600773 ER PT J AU Khan, M Stoler, MH Schiffman, M AF Khan, M Stoler, MH Schiffman, M CA ALTS Grp TI The yield of endocervical curretage (ECC) in the work-up of cervical intraepithelial neoplasia SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 873 BP 188A EP 188A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601046 ER PT J AU Ning, EMLL Ricketts, RSJ Palau, MA Otis, C Roberts, DD Merino, MJ AF Ning, EMLL Ricketts, RSJ Palau, MA Otis, C Roberts, DD Merino, MJ TI In search of new molecular markers in the diagnosis of endometrial cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Springfield, MA 01199 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 890 BP 191A EP 192A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601063 ER PT J AU Elghetany, MT Bryant, B Alter, BP AF Elghetany, MT Bryant, B Alter, BP TI Bone marrow expression of p53, caspase-3, and WT-1 proteins in inherited and acquired cytopenias: A study of 106 patients SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Texas, Med Branch, Galveston, TX 77555 USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1063 BP 229A EP 229A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601236 ER PT J AU Fu, K Dave, S Wright, G Weisenburger, DD Greiner, TC Ott, G Muller-Hermelink, HK Rimsza, LM Braziel, RM Gascoyne, RD Delabie, J Campo, E Jaffe, ES Chiorazzi, M Zhao, H Chan, WC Staudt, LM AF Fu, K Dave, S Wright, G Weisenburger, DD Greiner, TC Ott, G Muller-Hermelink, HK Rimsza, LM Braziel, RM Gascoyne, RD Delabie, J Campo, E Jaffe, ES Chiorazzi, M Zhao, H Chan, WC Staudt, LM TI Molecular diagnosis of Burkitt lymphoma using gene expression profiling SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Nebraska, Med Ctr, Lincoln, NE 68583 USA. NCI, Bethesda, MD 20892 USA. Univ Wurzburg, D-97070 Wurzburg, Germany. Univ Arizona, Tucson, AZ 85721 USA. Univ Oregon, Eugene, OR 97403 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, E-08007 Barcelona, Spain. Norwegian Radium Hosp, Oslo, Norway. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1067 BP 230A EP 230A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601240 ER PT J AU Greiner, T Hacia, J Rosenwald, A Weisenburger, D Smith, L Jaffe, E Gascoyne, R Campo, E Mueller-Hermelink, K Ott, G Delabie, J Braziel, R Staudt, L Chan, W AF Greiner, T Hacia, J Rosenwald, A Weisenburger, D Smith, L Jaffe, E Gascoyne, R Campo, E Mueller-Hermelink, K Ott, G Delabie, J Braziel, R Staudt, L Chan, W TI MRNA expression profile of p53 mutant or ATM mutant cases of mantle cell lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Univ So Calif, Los Angeles, CA USA. Univ Wurzburg, Wurzburg, Germany. NCI, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, Barcelona, Spain. Norwegian Radium Hosp, Oslo, Norway. Univ Oregon, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1077 BP 232A EP 232A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601250 ER PT J AU Martinez, A Pittaluga, S Rudelius, M Foumaine, T Jaffe, ES Raffeld, M AF Martinez, A Pittaluga, S Rudelius, M Foumaine, T Jaffe, ES Raffeld, M TI Activation of the plasma cell associated transcription factor XBP-1 in B-cell NHL SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Natl Canc Inst, Bethesda, MD USA. Hosp del Mar, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1117 BP 241A EP 241A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601290 ER PT J AU Ozer, O Lee, S Jayathilaka, N Shi, R Sun, M Ge, X Bouffard, G Wang, SM Rowley, JD AF Ozer, O Lee, S Jayathilaka, N Shi, R Sun, M Ge, X Bouffard, G Wang, SM Rowley, JD TI Unique gene expression profiles and novel transcripts in acute myeloid leukemia with recurrent translocations identified by SAGE (serial analysis of gene expression SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Univ Chicago, Chicago, IL 60637 USA. Northwestern Univ, Evanston, IL USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1134 BP 244A EP 245A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601307 ER PT J AU Prakash, S Fountaine, T Raffeld, M Jaffe, ES Pittaluga, S AF Prakash, S Fountaine, T Raffeld, M Jaffe, ES Pittaluga, S TI IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1144 BP 247A EP 247A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601317 ER PT J AU Warren, MV Howat, WJ Haynes, B McCafferty, J Fredrickson, TN AF Warren, MV Howat, WJ Haynes, B McCafferty, J Fredrickson, TN TI Pathology of haernopoietic neoplasms arising in blm deficient mice: Use of tissue microarrays for high throughput immunohistochemical analysis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Sanger Inst, Cambridge, England. Addenbrookes Hosp, Cambridge, England. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1185 BP 256A EP 256A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601358 ER PT J AU Berhane, D Mannon, RB Swanson, SJ Hale, DA Kirk, AD Kleiner, DE AF Berhane, D Mannon, RB Swanson, SJ Hale, DA Kirk, AD Kleiner, DE TI Quantitative assessment of glomerular infiltrates in chronic allograft glomerulopathy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Howard Univ, Washington, DC 20059 USA. NIDDKD, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1227 BP 265A EP 265A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601400 ER PT J AU Calvo, KR Espina, V Rodriguez, A Hoatson, S Petricoin, EF Alexander, HR Liotta, LA Pingpank, JF AF Calvo, KR Espina, V Rodriguez, A Hoatson, S Petricoin, EF Alexander, HR Liotta, LA Pingpank, JF TI Clinical proteomics: In vivo molecular signaling profiles of human tumors, pre and post tumor perfusion with experimental chemotherapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1372 BP 297A EP 297A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601545 ER PT J AU Henson, DE Tilara, A Anderson, WA Schwartz, A AF Henson, DE Tilara, A Anderson, WA Schwartz, A TI Similar age-specific incidence rate patterns imply a biological relationship for ovarian cancers SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 George Washington Univ, Med Ctr, Washington, DC 20037 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1377 BP 298A EP 298A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601550 ER PT J AU Galli, S Tsokos, M AF Galli, S Tsokos, M TI Myogenin and MyoD expression in pediatric rhabdomyosarcoma (RMS) and other soft tissue tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1404 BP 303A EP 304A PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601577 ER PT J AU Funkhouser, WK Flake, GP Maygarden, SJ Detterbeck, FC Rivera, MP Slebos, RJC Taylor, JA AF Funkhouser, WK Flake, GP Maygarden, SJ Detterbeck, FC Rivera, MP Slebos, RJC Taylor, JA TI Detection of new primary in situ and invasive squamous lung carcinomas in patients with and without a history of lung or ENT squamous carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 UNC, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1437 BP 310A EP 310A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601609 ER PT J AU Shilo, K Fukuoka, J Foss, RD Franks, TJ Travis, WD AF Shilo, K Fukuoka, J Foss, RD Franks, TJ Travis, WD TI Comparative immunohistochemical analysis of mucoepidermoid and adenoid cystic carcinomas of pulmonary and salivary gland origin SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1475 BP 318A EP 318A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601647 ER PT J AU Palau, M Ronchetti, R Linehan, WM Ning, EML Torres-Cabala, C Merino, MJ AF Palau, M Ronchetti, R Linehan, WM Ning, EML Torres-Cabala, C Merino, MJ TI Application of chromogenic in situ hybridization (CISH) in the differential diagnosis of renal tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1545 BP 333A EP 333A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601717 ER PT J AU Sorbara, L Dieffenbach, S Pham, T Pham, TH Raffeld, M AF Sorbara, L Dieffenbach, S Pham, T Pham, TH Raffeld, M TI A simple one-tube method for DNA isolation and polymerase chain amplification of fresh and paraffin-embedded tissues SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1553 BP 335A EP 335A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601725 ER PT J AU Ahmed, A Torres-Cabala, C Linehan, M Merino, M Tsokos, M AF Ahmed, A Torres-Cabala, C Linehan, M Merino, M Tsokos, M TI Renal tumors in hereditary Leiomyomatosis renal cell carcinoma syndrome: Ultrastructural characterization SO LABORATORY INVESTIGATION LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. Ctr Canc Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2005 VL 85 SU 1 MA 1566 BP 337A EP 337A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 886OQ UT WOS:000226238601738 ER PT J AU Morales, VE AF Morales, VE TI More debate on the issue of state mandated licensure SO LABORATORY MEDICINE LA English DT Letter C1 NIH, Serv Immunol, Dept Lab Med, Bethesda, MD 20892 USA. RP Morales, VE (reprint author), NIH, Serv Immunol, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD JAN PY 2005 VL 36 IS 1 BP 58 EP 58 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 883CV UT WOS:000225988700020 ER PT J AU Pace, CA Emanuel, EJ AF Pace, CA Emanuel, EJ TI The ethics of research in developing countries: assessing voluntariness SO LANCET LA English DT Editorial Material ID AFRICA C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Emanuel, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 14 TC 18 Z9 18 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN 1 PY 2005 VL 365 IS 9453 BP 11 EP 12 DI 10.1016/S0140-6736(04)17679-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 886FU UT WOS:000226213100008 PM 15639664 ER PT J AU Nichols, WC Pankratz, N Hernandez, D Paisan-Ruiz, C Jain, S Halter, CA Michaels, VE Reed, T Rudolph, A Shults, CW Singleton, A Foroud, T AF Nichols, WC Pankratz, N Hernandez, D Paisan-Ruiz, C Jain, S Halter, CA Michaels, VE Reed, T Rudolph, A Shults, CW Singleton, A Foroud, T CA Parkinson Study Grp PROGENI Invest TI Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease SO LANCET LA English DT Article ID SAMPLE AB Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause some forms of autosomal dominant Parkinson's disease. We measured the frequency of a novel mutation (Gly2019Ser) in familial Parkinson's disease by screening genomic DNA of patients and controls. Of 767 affected individuals from 358 multiplex families, 35 (5%) individuals were either heterozygous (34) or homozygous (one) for the mutation, and had typical clinical findings of idiopathic Parkinson's disease. Thus, our results suggest that a single LRRK2 mutation causes Parkinson's disease in 5% of individuals with familial disease. Screening for this mutation should be a component of genetic testing for Parkinson's disease. C1 Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. Indiana Univ, Med Ctr, Dept Med & Mol Genet, Indianapolis, IN USA. NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. CSIC, Dept Genom & Proteom, Inst Biomed Valencia, Unitat Genet Mol, Valencia, Spain. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Univ Rochester, Dept Neurol, Rochester, NY USA. Univ Calif, Dept Neurosci, La Jolla, CA USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. RP Nichols, WC (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Human Genet, 3333 Burnet Ave,1469 TCHRF, Cincinnati, OH 45229 USA. EM Bill.nichols@cchmc.org RI Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009 FU NCRR NIH HHS [M01 RR-00750]; NIA NIH HHS [AG18736]; NINDS NIH HHS [NS37167] NR 7 TC 297 Z9 306 U1 0 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JAN-FEB PY 2005 VL 365 IS 9457 BP 410 EP 412 DI 10.1016/S0140-6736(05)17828-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 891WE UT WOS:000226610900027 PM 15680455 ER PT J AU Gilks, WP Abou-Sleiman, PM Gandhi, S Jain, S Singleton, A Lees, AJ Shaw, K Bhatia, KP Bonifati, V Quinn, NP Lynch, J Healy, DG Holton, JL Revesz, T Wood, NW AF Gilks, WP Abou-Sleiman, PM Gandhi, S Jain, S Singleton, A Lees, AJ Shaw, K Bhatia, KP Bonifati, V Quinn, NP Lynch, J Healy, DG Holton, JL Revesz, T Wood, NW TI Common LRRK2 mutation in idiopathic Parkinson's disease SO LANCET LA English DT Article AB Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene have been shown to cause autosomal dominant Parkinson's disease. Few mutations in this gene have been identified. We investigated the frequency of a common heterozygous mutation, 2877510G-->A, which produces a glycine to serine aminoacid substitution at codon 2019 (Gly2019Ser), in idiopathic Parkinson's disease. We assessed 482 patients with the disorder, of whom 263 had pathologically confirmed disease, by direct sequencing for mutations in exon 41 of LRRK2. The mutation was present in eight (1.6%) patients. We have shown that a common single Mendelian mutation is implicated in sporadic Parkinson's disease. We suggest that testing for this mutation will be important in the management and genetic counselling of patients with Parkinson's disease. C1 Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Inst Neurol, Dept Motor Neurosci, London WC1N 3BG, England. UCL Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. Reta Lila Weston Inst Neurol Studies, London, England. RP Wood, NW (reprint author), Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM n.wood@ion.ucLac.uk RI Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009; Wood, Nicholas/C-2505-2009; Gilks, William/P-9137-2015; Holton, Janice/F-6831-2011; Revesz, Tamas/A-8732-2010 OI Wood, Nicholas/0000-0002-9500-3348; Gilks, William/0000-0001-7814-3173; Holton, Janice/0000-0002-3882-5249; Revesz, Tamas/0000-0003-2501-0259 FU Parkinson's UK [G-4029, G-4062] NR 5 TC 442 Z9 457 U1 2 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN-FEB PY 2005 VL 365 IS 9457 BP 415 EP 416 DI 10.1016/S0140-6736(05)17830-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 891WE UT WOS:000226610900029 PM 15680457 ER PT J AU Restifo, NP Rosenberg, SA AF Restifo, NP Rosenberg, SA TI Use of standard criteria for assessment of cancer vaccines SO LANCET ONCOLOGY LA English DT Editorial Material ID SOLID TUMORS; T-CELLS; REGRESSION C1 NIH, US Natl Canc Inst, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NIH, US Natl Canc Inst, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 7 TC 15 Z9 18 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2005 VL 6 IS 1 BP 3 EP 4 PG 2 WC Oncology SC Oncology GA 887XZ UT WOS:000226340100005 PM 15629270 ER PT J AU Limb, CJ Long, DM Niparko, JK AF Limb, CJ Long, DM Niparko, JK TI Acoustic neuromas after failed radiation therapy: Challenges of surgical salvage SO LARYNGOSCOPE LA English DT Article DE acoustic neuroma surgery; gamma knife; stereotactic radiosurgery; surgical salvage; vestibular schwannoma ID FACIAL-NERVE; STEREOTACTIC RADIOSURGERY; MIDDLE FOSSA; SURGERY; PRESERVATION; MANAGEMENT AB Objectives. As stereotactic radiation has emerged as a treatment option for acoustic neuromas, cases that require surgical salvage after unsuccessful radiation have emerged. We present a comparison of the technical challenges faced by the surgeons in the treatment of irradiated versus nonirradiated acoustic neuromas. Study Design: Matched case-control series. Methods. We identified nine patients with acoustic neuromas that required surgical resection after radiation therapy. Cases were performed with suboccipital and translabyrinthine approaches. Nine nonirradiated case-control subjects matched for age, sex, tumor size, and surgical approach were identified for purposes of general comparison. Operative findings and outcomes were compared for the two groups. Results. Surgical removal was found to he significantly more difficult after radiation therapy because of increased fibrosis and adhesion to adjacent nervous structures, particularly at the porus acousticus. Excessive scarring hindered identification of the facial nerve and added uncertainty as to the completeness of tumor removal. Decompression of the internal auditory canal (IAC) dura and resection of neoplasm in the IAC before cerebellopontine angle dissection was required for facial nerve identification. Operative time was significantly longer for irradiated cases, and facial nerve outcomes tended to be poorer, particularly when facial nerve dysfunction prompted the salvage procedure. Conclusions. Surgical salvage of acoustic neuromas after radiation therapy is feasible, but it presents technical challenges beyond that associated with primary surgical therapy. Poorer outcomes of postoperative cranial nerve status were caused primarily by anatomic changes at the nerve/tumor interface. As surgical experience with the irradiated acoustic neuroma grows, operative observations should be incorporated into the counsel provided to patients with acoustic neuromas as they weigh different management options. C1 Johns Hopkins Univ Hosp, Johns Hopkins Outpatient Ctr, Dept Otolaryngol, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Limb, CJ (reprint author), Johns Hopkins Univ Hosp, Johns Hopkins Outpatient Ctr, Dept Otolaryngol, 6th Floor,601 N Caroline St, Baltimore, MD 21287 USA. EM climb@jhmi.edu NR 14 TC 29 Z9 31 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 2005 VL 115 IS 1 BP 93 EP 98 DI 10.1097/01.mlg.0000150686.93011.49 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 887YF UT WOS:000226340700019 PM 15630374 ER PT J AU Sconocchia, G Keyvanfar, K El Ouriaghli, F Grube, M Rezvani, K Fujiwara, H McCoy, JP Hensel, N Barrett, AJ AF Sconocchia, G Keyvanfar, K El Ouriaghli, F Grube, M Rezvani, K Fujiwara, H McCoy, JP Hensel, N Barrett, AJ TI Phenotype and function of a CD56+peripheral blood monocyte SO LEUKEMIA LA English DT Article DE NK cells; monocytes; macrophages; cellular proliferation; cellular differentiation ID NATURAL-KILLER-CELLS; HUMAN PERIPHERAL-BLOOD; ADHESION MOLECULE; LYMPHOCYTES-T; MACROPHAGES; EXPRESSION; SUBSET; CYTOTOXICITY; IDENTIFICATION; SUBPOPULATION AB G-CSF primed CD34 cells cultured for 2-3 weeks in IL-2 and stem cell factor generate CD56(high) cells with phenotypic and morphologic features of NK cells, and a novel adherent CD56(low) CD16-population expressing myeloid markers (CD33 and HLA-DR). We hypothesized that similar cells might also occur in peripheral blood. In 13/13 normal individuals, we found a circulating population of CD56 (low), CD33 +, FcgammaRI +, FcgammaRII +, HLA-DR +, CD11b(high), CD14 + monocytes closely resembling the cultured CD56(low) CD33 + cells. They may represent a normal counterpart of the CD56 + CD33 + hybrid myeloid/natural killer cell leukemia. Their mean frequency was 1.3+/-1% (standard deviation), range 0.16-3.5%, of total mononuclear cells. CD56(low) CD33 + cells, primed with cytomegalovirus antigen, induced autologous T-lymphocyte proliferation comparably to CD56-, CD14 + peripheral blood monocytes (PBM). Conversely, CD56(low) cells induced greater T-cell proliferation than CD56- PBM when lymphocyte responders were HLA mismatched. Unstimulated CD56(low) CD33 + cells showed a low antiproliferative effect on K562, which was increased upon LPS stimulation. The pattern of cytokine production by CD56(low) CD33 + cells and PBM largely overlapped; however, they produced detectable levels of IL-6 and IL-1beta. These results define a minor monocyte population with distinct phenotypic and functional features. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, Hematopoiet Stem Cell Transplantat Sect, NIH, Bethesda, MD 20892 USA. EM barretj@nhlbi.nih.gov NR 40 TC 28 Z9 30 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2005 VL 19 IS 1 BP 69 EP 76 DI 10.1038/sj.leu.2403550 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 879IR UT WOS:000225710700013 PM 15526027 ER PT J AU Valent, P Akin, C Sperr, WR Mayerhofer, M Fodinger, M Fritsche-Polanz, R Sotlar, K Escribano, L Arock, M Horny, HP Metcalfe, DD AF Valent, P Akin, C Sperr, WR Mayerhofer, M Fodinger, M Fritsche-Polanz, R Sotlar, K Escribano, L Arock, M Horny, HP Metcalfe, DD TI Mastocytosis: Pathology, genetics, and current options for therapy SO LEUKEMIA & LYMPHOMA LA English DT Review DE mast cells; mastocytosis; classification; criteria ID MAST-CELL DISEASE; C-KIT MUTATION; ACUTE MYELOID-LEUKEMIA; AGGRESSIVE SYSTEMIC MASTOCYTOSIS; BLOOD MONONUCLEAR-CELLS; COLONY-FORMING CELL; BONE-MARROW; GENERALIZED MASTOCYTOSIS; CUTANEOUS-MASTOCYTOSIS; URTICARIA PIGMENTOSA AB Mast cell disorders are defined by an abnormal accumulation of tissue mast cells (MCs) in one or more organ systems. Symptoms in mastocytosis result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Cutaneous mastocytosis ( CM) is a benign disease of the skin and may regress spontaneously. Systemic mastocytosis (SM) is a persistent disease in which a somatic c-kit mutation at codon 816 is usually detectable in MCs and their progenitors. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. The WHO discriminates five categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with associated clonal hematological non-MC-lineage disease (AHNMD), and mast cell leukemia (MCL). The c-kit mutation D816V is quite common and may be found in all SM-categories. In SM-AHNMD, additional genetic abnormalities have been reported, whereas no additional defects are yet known for ASM or MCL. Patients with ISM and CM are treated with "mediator-targeting'' drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy. The use of "Kit-targeting'' tyrosine kinase inhibitors such as STI571 ( Imatinib, Gleevec), has also been suggested. However, the D816V mutation of c-kit is associated with relative resistance against STI571. Therefore, these patients require alternative targeted drugs or new drug-combinations. In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established. Examples include the use of STI571 in patients with SM plus hypereosinophilic syndrome (SM-HES) and the FIPL1/PDGFRA fusion gene target, or chemotherapy for eradication of AML in patients with SM-AML. C1 Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Vienna, Austria. Univ Michigan, Div Allergy, Ann Arbor, MI 48109 USA. Med Univ Vienna, Clin Inst Med & Chem Lab Diagnost, Vienna, Austria. Univ Tubingen, Inst Pathol, D-72074 Tubingen, Germany. Hosp Ramon y Cajal, Mast Cell Unit, E-28034 Madrid, Spain. Fac Pharm, CNRS, Unit UMR 8147, Paris, France. Univ Lubeck, Inst Pathol, Lubeck, Germany. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Valent, P (reprint author), Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Wahringer Gurtel 18-20, Vienna, Austria. EM peter.valent@meduniwien.ac.at OI Akin, Cem/0000-0001-6301-4520 NR 122 TC 145 Z9 148 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2005 VL 46 IS 1 BP 35 EP 48 DI 10.1080/10428190400010775 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 881OV UT WOS:000225877700005 PM 15621779 ER PT J AU Gohagan, JK Marcus, PM Fagerstrom, RM Pinsky, PF Kramer, BS Prorok, PC Ascher, S Bailey, W Brewer, B Church, T Engelhard, D Ford, M Fouad, M Freedman, M Gelmann, E Gierada, D Hocking, W Inampudi, S Irons, B Johnson, CC Jones, A Kucera, G Kvale, P Lappe, K Manor, W Moore, A Nath, H Neff, S Oken, M Plunkett, M Price, H Reding, D Riley, T Schwartz, M Spizarny, D Yoffie, R Zylak, C AF Gohagan, JK Marcus, PM Fagerstrom, RM Pinsky, PF Kramer, BS Prorok, PC Ascher, S Bailey, W Brewer, B Church, T Engelhard, D Ford, M Fouad, M Freedman, M Gelmann, E Gierada, D Hocking, W Inampudi, S Irons, B Johnson, CC Jones, A Kucera, G Kvale, P Lappe, K Manor, W Moore, A Nath, H Neff, S Oken, M Plunkett, M Price, H Reding, D Riley, T Schwartz, M Spizarny, D Yoffie, R Zylak, C CA Lung Screening Study Research Grp TI Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer SO LUNG CANCER LA English DT Article DE chest X-ray; lung cancer; randomized trial; screening; spiral CT ID COMPUTED-TOMOGRAPHY; TRIAL AB The Lung Screening Study (LSS) was a pilot study designed to assess the feasibility of conducting a large scale randomized controlled trial (RCT) of low radiation dose spiral computed tomography (LDCT) versus chest X-ray (CXR) for lung cancer screening. Baseline results of LSS have been previously reported. Here, we report on the findings at the year one screen and on the final results of the LSS study. A total of 1660 subjects were randomized to the LDCT arm and 1658 to the CXR arm. Compliance with screening declined from 96% at baseline to 86% at year one in the LDCT arm and declined from 93% at baseline to 80% at year one in the CXR arm. Positivity rates for the year one screen were 25.8% for LDCT and 8.7% for CXR. Cancer yield was significantly less at year one for LDCT, 0.57%, than at baseline, 1.9%; cancer yield for CXR increased from 0.45% at baseline to 0.68% at year one. Forty lung cancers in the LDCT arm and 20 in the CXR arm were diagnosed over the study period. Stage I cancers comprised 48% of cases in the LDCT arm and 40% in the CXR arm. A total of 16 stage III-IV cancers were observed in the LDCT arm versus nine in the CXR arm. The LSS has established the feasibility of a RCT comparing annual spiral CT to chest X-ray for lung cancer screening. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov OI Hocking, William/0000-0002-0690-3759; Johnson, Christine Cole/0000-0002-6864-6604; Church, Timothy R./0000-0003-3292-5035 NR 14 TC 159 Z9 164 U1 3 U2 13 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JAN PY 2005 VL 47 IS 1 BP 9 EP 15 DI 10.1016/j.lungcan.2004.06.007 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 891IS UT WOS:000226575100002 PM 15603850 ER PT J AU Balow, JE AF Balow, JE TI Clinical presentation and monitoring of lupus nephritis SO LUPUS LA English DT Article DE lupus nephritis; lupus serologies; renal function; urine sediment ID CREATININE RATIO; REVISED CRITERIA; ERYTHEMATOSUS; CLASSIFICATION; PROTEINURIA; DISEASE AB The diversity of clinical presentations of lupus nephritis parallel the diversity of pathologic lesions seen in the kidneys of patients with SLE. Renal manifestations range from asymptomatic hematuria or proteinuria to overt nephritic and nephrotic syndromes, rapidly progressive glomerulonephritis, and chronic renal failure. Subclinical nephropathy both during presentation and during monitoring of disease activity is frequently missed because of the notorious unreliability of routine screening urinalyses performed in high-throughput clinical pathology laboratories. Requisitions for urine microscopy should be flagged for special attention in patients at risk for lupus nephritis. Depression of classic complement pathway components and high titers of anti-DNA, anti- nucleosome, or anti-C1q antibodies identify patients are increased risk of renal involvement or flares of nephritis. Several disease activity and damage indexes are available, but they are mostly used in clinical research setting and none has achieved wide use for standard clinical practice. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Balow, JE (reprint author), NIDDKD, Kidney Dis Sect, NIH, Bldg 10,Room 9N-222, Bethesda, MD 20892 USA. EM james.e.balow@nih.gov NR 22 TC 57 Z9 61 U1 1 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2005 VL 14 IS 1 BP 25 EP 30 DI 10.1191/0961203305lu2055oa PG 6 WC Rheumatology SC Rheumatology GA 895XM UT WOS:000226897700005 PM 15732284 ER PT J AU Austin, HA Illei, GG AF Austin, HA Illei, GG TI Membranous lupus nephritis SO LUPUS LA English DT Article DE classification; pathogenesis; prognosis; treatment ID NONDIABETIC RENAL-DISEASE; NEPHROTIC SYNDROME; CONTROLLED TRIAL; SINGLE-CENTER; RISK-FACTOR; NEPHROPATHY; ERYTHEMATOSUS; PROGNOSIS; GLOMERULONEPHRITIS; CLASSIFICATION AB Membranous lupus nephritis (MLN) represents about 20% of clinically significant renal disease in lupus. Few studies have addressed directly the pathogenesis of MLN. Our assumptions about the underlying mechanisms are based on the combination of extrapolations from idiopathic membranous nephritis ( mainly from animal models) and proliferative lupus nephritis. Natural history studies of MLN suggest a relatively low rate of progression to end-stage renal disease but a high rate of significant comorbidities. Historical changes in the criteria for pathologic diagnosis and classification of membranous lupus nephropathy have precluded definitive descriptions of the natural history, prognosis and treatment of this disorder. Patients with membranous lupus nephropathy should be treated early with angiotensin antagonists to minimize proteinuria, as well as lifestyle changes and appropriate drugs to reduce attendant cardiovascular risk factors. In patients with protracted nephrotic syndrome, consideration should be given to immunosuppressive therapies, including corticosteroids, cyclosporine, mycophenolate and cyclophosphamide. Prospective controlled trials are clearly needed in order to establish solid clinical practice guidelines for use of these drugs and other experimental therapies currently under study in membranous lupus nephropathy. C1 NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), NIAMSD, NIH, Dept Hlth & Human Serv, Bldg 10,Room 1N114, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov NR 42 TC 39 Z9 42 U1 0 U2 3 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2005 VL 14 IS 1 BP 65 EP 71 DI 10.1191/0961203305lu2062oa PG 7 WC Rheumatology SC Rheumatology GA 895XM UT WOS:000226897700012 PM 15732291 ER PT J AU Illei, GG AF Illei, GG TI On the road to the optimal treatment of lupus nephritis: are we there yet? SO LUPUS LA English DT Editorial Material ID INTRAVENOUS CYCLOPHOSPHAMIDE; THERAPY; TRIAL C1 NIH, US Dept Hlth & Human Serv, Gene Therapy & Therapeut Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), NIH, US Dept Hlth & Human Serv, Gene Therapy & Therapeut Branch, Natl Inst Dent & Craniofacial Res, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2005 VL 14 IS 4 BP 263 EP 264 DI 10.1191/0961203305lu2101ed PG 2 WC Rheumatology SC Rheumatology GA 919AH UT WOS:000228590200001 PM 15864911 ER PT J AU Mozes, E Lovchik, J Zinger, H Singer, DS AF Mozes, E Lovchik, J Zinger, H Singer, DS TI MHC class I expression regulates susceptibility to spontaneous autoimmune disease in (NZBxNZW)F1 mice SO LUPUS LA English DT Article DE class 1 deficient (NZBxNZW)F1 mice; experimental SLE; MHC class 1 ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; VERSUS-HOST-DISEASE; T-CELLS; DEFICIENT MICE; MURINE LUPUS; INDUCTION; METHIMAZOLE AB (NZBxNZW)F1 mice spontaneously develop with age an autoimmune disease that resembles the human disease, systemic lupus erythematosus (SLE). Previous studies have demonstrated that susceptibility to experimentally induced SLE depended on the expression of MHC class I molecules: mice deficient in beta 2-microglobulin did not express cell surface class I and were resistant to the induction of experimental SLE. Furthermore, the spontaneous SLE-like disease of (NZBxNZW)F1 mice was ameliorated by treatment with an agent that reduces MHC class I expression, methimazole (MMI). In the present study, the role of MHC class I has been examined in (NZBxNZW)F1 mice deficient in beta 2-microglobulin expression. Homozygous (NZBxNZW)F1 beta 2m(-/-) mice do not express class I or develop CD8+ T cells. Surprisingly, they show an increased susceptibility to disease. In sharp contrast, heterozygous (NZBxNZW)F1 beta 2m(+/-) express class I, albeit at reduced levels, develop normal levels of CD8+ T cells and are less susceptible to autoimmune disease, relative to their wild-type litter mates. Taken together, these findings suggest that class I expression regulates the development of disease, both positively and negatively. We speculate that MHC class I expression itself confers susceptibility to disease through presentation of self-peptides, while also selecting for a CD8+ suppressor T cell population that mitigates disease. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, Bldg 10,Room 4B-36, Bethesda, MD 20892 USA. EM dinah.singer@nih.gov NR 22 TC 15 Z9 17 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2005 VL 14 IS 4 BP 308 EP 314 DI 10.1191/0961203305lu2079oa PG 7 WC Rheumatology SC Rheumatology GA 919AH UT WOS:000228590200007 PM 15864917 ER PT J AU McCune, W Saluja, M Bhat, S Lange, LA Holzman, L Johnson, K AF McCune, W Saluja, M Bhat, S Lange, LA Holzman, L Johnson, K TI Correlation of membranous glomerular ultrastructural changes with disease severity and outcome in lupus patients initiating cyclophosphamide therapy SO LUPUS LA English DT Article DE cyclophosphamide; electron microscopy; lupus nephritis; membranous nephritis; renal biopsy ID RENAL BIOPSY; PATHOLOGIC FEATURES; NEPHRITIS; ERYTHEMATOSUS; GLOMERULONEPHRITIS; CLASSIFICATION; NEPHROPATHY; INFORMATION; PREDICTORS; PROGNOSIS AB The aim of this study was to assess the utility applying an electron microscopy (EM) scoring system used in idiopathic membranous nephritis based on the location of subepithelial and/or intramembranous electron dense deposits in interpretation of renal biopsies from patients with lupus nephritis. We selected patients with electron dense deposits traditionally associated with membranous changes on EM from 84 patients treated with bolus cyclophosphamide, with five years follow-up. An EM scoring system designed for idiopathic membranous nephritis was applied (stages I or II, mild changes; stages III or IV, advanced changes). Twenty-seven out of 84 had membranous changes by light microscopy, of whom 22 had satisfactory tissue for EM membranous analysis. Eleven out of 22 had mild EM changes (EM stage I or II),- 11 had advanced disease (EM stage III). Advanced EM stage was associated with a higher serum creatinine at entry when tests were adjusted for WHO class (2.62 +/- 0.6 versus 1.31 +/- 0.28 mg/dL, P < 0.022 by ANOVA), and EM stage was independent of NIH activity or chronicity indexes or disease duration. After five years, adverse outcomes (death or dialysis) were seen in one of the 11 patients with EM stages I-II versus five of the 11 EM stage III patients (P < 0.07). Advanced membranous type electron dense deposition in lupus as assessed by EM was associated with worse renal function in patients with comparable WHO classification and NIH activity and chronicity indexes. In this group of lupus patients initiating cyclophosphamide for severe nephritis, EM stage provided important additional information regarding the extent of renal injury. C1 Univ Michigan, Clin Res Ctr, NIH, Ann Arbor, MI 48109 USA. RP McCune, W (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, 1500 E Med Ctr Dr,Taubman 3918, Ann Arbor, MI 48109 USA. EM jmccune@umich.edu FU NCRR NIH HHS [M01-RR00042] NR 23 TC 2 Z9 2 U1 0 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 2005 VL 14 IS 6 BP 426 EP 433 DI 10.1191/0961203305lu2105oa PG 8 WC Rheumatology SC Rheumatology GA 945OQ UT WOS:000230512400003 PM 16038105 ER PT J AU Larson, AC Kellman, P Arai, A Hirsch, GA McVeigh, E Li, DB Simonetti, OP AF Larson, AC Kellman, P Arai, A Hirsch, GA McVeigh, E Li, DB Simonetti, OP TI Preliminary investigation of respiratory self-gating for free-breathing segmented cine MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CMR; gating; triggering; navigator; cine ID CORONARY ANGIOGRAPHY; ACQUISITION; IMAGES; HEART AB Segmented cine MRI generally requires breath-holding, which can be problematic for many patients. Navigator echo techniques, particularly successful for free-breathing coronary MRA, are incompatible with the acquisition strategies and SSFP pulse sequences commonly used for cine MRI. The purpose of this work is to introduce a new self-gating technique deriving respiratory gating information directly from the raw imaging data acquired for segmented cine MRI. The respiratory self-gating technique uses interleaved radial k-space sampling to provide low-resolution images in real time during the free-breathing acquisition that are compared to target expiration images. Only the raw data-producing images with high correlation to the target images are included in the final high-resolution reconstruction. The self-gating technique produced cine series with no significant differences in quantitative image sharpness to series produced using comparable breath-held techniques. Because of the difficulties associated with breath-holding, the respiratory self-gating technique represents an important practical advance for cardiac MRI. Published 2004 Wiley-Liss, Inc. C1 Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. Northwestern Univ, Dept Biomed Engn, Chicago, IL 60611 USA. NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. Siemens Med Solut, Malvern, PA USA. RP Larson, AC (reprint author), Northwestern Univ, Dept Radiol, 448 E Ontario Suite 700,, Chicago, IL 60611 USA. EM alarson@radiology.northwestern.edu RI Li, Debiao/B-7622-2009; Simonetti, Orlando/E-4098-2011 FU Intramural NIH HHS [Z01 HL004608-08] NR 29 TC 81 Z9 82 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2005 VL 53 IS 1 BP 159 EP 168 DI 10.1002/mrm.20331 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 888NE UT WOS:000226380700022 PM 15690515 ER PT J AU Ennis, DB Kindlman, G Rodriguez, I Helm, PA McVeigh, ER AF Ennis, DB Kindlman, G Rodriguez, I Helm, PA McVeigh, ER TI Visualization of tensor fields using superquadric glyphs SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion; tensor; myocardium; fiber angle ID CANINE LEFT-VENTRICLE; DIFFUSION TENSOR; HUMAN BRAIN; ORIENTATION; ANISOTROPY; TISSUES AB The spatially varying tensor fields that arise in magnetic resonance imaging are difficult to visualize due to the multivariate nature of the data. To improve the understanding of myocardial structure and function a family of objects called glyphs, derived from superquadric parametric functions, are used to create informative and intuitive visualizations of the tensor fields. The superquadric glyphs are used to visualize both diffusion and strain tensors obtained in canine myocardium. The eigensystem of each tensor defines the glyph shape and orientation. Superquadric functions provide a continuum of shapes across four distinct eigensystems (lambda(i), sorted eigenvalues), lambda(1) = lambda(2) = lambda(3) (spherical), lambda(1) < lambda(2) = lambda(3) (oblate), lambda(1) > lambda(2) = lambda(3) (prolate), and lambda(1) > lambda(2) > lambda(3) (cuboid). The superquadric glyphs are especially useful for identifying regions of anisotropic structure and function. Diffusion tensor renderings exhibit fiber angle trends and orthotropy (three distinct eigenvalues). Visualization of strain tensors with superquadric glyphs compactly exhibits radial thickening gradients, circumferential and longitudinal shortening, and torsion combined. The orthotropic nature of many biologic tissues and their DTMRI and strain data require visualization strategies that clearly exhibit the anisotropy of the data if it is to be interpreted properly. Superquadric glyphs improve the ability to distinguish fiber orientation and tissue orthotropy compared to ellipsoids. Published 2004 Wiley-Liss, lnc. C1 NHLBI, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Univ Utah, Sci Comp Imaging Inst, Salt Lake City, UT USA. RP Ennis, DB (reprint author), Stanford Univ, Dept Radiol, Lucas MRII Ctr, Mail Code 5488,Route 8, Stanford, CA 94305 USA. EM dbe@stanford.edu RI Rodriguez, Ignacio/B-1006-2015 OI Rodriguez, Ignacio/0000-0002-4262-2516 FU Intramural NIH HHS [Z01 HL004608-08] NR 19 TC 29 Z9 29 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2005 VL 53 IS 1 BP 169 EP 176 DI 10.1002/mrm.20318 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 888NE UT WOS:000226380700023 PM 15690516 ER PT J AU Kellman, P Larson, AC Hsu, LY Chung, YC Simonetti, OP McVeigh, ER Arai, AE AF Kellman, P Larson, AC Hsu, LY Chung, YC Simonetti, OP McVeigh, ER Arai, AE TI Motion-corrected free-breathing delayed enhancement Imaging of myocardial infarction SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; delayed enhancement; heart; myocardial infarction; phase sensitive; SENSE; parallel MRI; free-breathing; motion correction ID REGISTRATION; MRI AB Following administration of Gd-DTPA, infarcted myocardium exhibits delayed enhancement and can be imaged using an inversion-recovery sequence. A conventional segmented acquisition requires a number of breath-holds to image the heart. Single-shot phase-sensitive inversion-recovery (PSIR) true-FISP may be combined with parallel imaging using SENSE to achieve high spatial resolution. SNR may be improved by averaging multiple motion-corrected images acquired during free breathing. PSIR techniques have demonstrated a number of benefits including consistent contrast and appearance over a relatively wide range of inversion recovery times (TI), improved contrast-to-noise ratio, and consistent size of the enhanced region. Comparison between images acquired using segmented breath-held turbo-FLASH and averaged, motion-corrected, free-breathing true-FISP show excellent agreement of measured CNR and infarct size. In this study, motion correction was implemented using image registration postprocessing rather than navigator correction of individual frames. Navigator techniques may be incorporated as well. Published 2004 Wiley-Liss, Inc. C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. Northwestern Univ, Dept Biomed Engn, Chicago, IL 60611 USA. Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. Siemens Med Solut, Chicago, IL USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov RI Simonetti, Orlando/E-4098-2011; OI Chung, Yiu-Cho/0000-0003-1003-8320 FU Intramural NIH HHS [Z01 HL004608-08] NR 19 TC 58 Z9 59 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2005 VL 53 IS 1 BP 194 EP 200 DI 10.1002/mrm.20333 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 888NE UT WOS:000226380700026 PM 15690519 ER PT S AU Blair, PL Carucci, DJ AF Blair, PL Carucci, DJ BE Sullivan, DJ Krishna, S TI Functional proteome and expression analysis of sporozoites and hepatic stages of malaria development SO MALARIA: DRUGS, DISEASE AND POST-GENOMIC BIOLOGY SE Current Topics in Microbiology and Immunology LA English DT Review ID PLASMODIUM-FALCIPARUM SPOROZOITES; SACCHAROMYCES-CEREVISIAE; EXOERYTHROCYTIC STAGE; DNA MICROARRAYS; GENOME SEQUENCE; BINDING PROTEIN; GENE-EXPRESSION; CULTURED-CELLS; HOST-CELLS; LIFE-CYCLE AB An evolution in modern malaria research occurred with the completion of the Plasmodium falciparum genome project and the onset and application of novel post-genomic technologies. Corresponding with these technological achievements are improvements in accessing and purifying parasite material from 'hard-to-reach' stages of malaria development. Characterization of gene and protein expression in the infectious sporozoite and subsequent liver-stage parasite development is critical to identify novel pre-erythrocytic drug and vaccine targets as well as to understand the basic biology of this deadly parasite. Both transcriptional and proteomic analyses on these stages and the remaining stages of development will assist in the 'credentialing process' of the complete malaria genome. C1 Earlham Coll, Dept Biol, Richmond, IN 47374 USA. Fdn Natl Inst Hlth, Bethesda, MD 20892 USA. RP Blair, PL (reprint author), Earlham Coll, Dept Biol, 801 Natl Rd W, Richmond, IN 47374 USA. EM blairpe@earlham.edu NR 71 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-25363-7 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2005 VL 295 BP 417 EP 438 PG 22 WC Immunology; Microbiology SC Immunology; Microbiology GA BDG89 UT WOS:000233456400016 PM 16265900 ER PT J AU Berezovsky, F Karev, G Song, B Castillo-Chavez, C AF Berezovsky, F Karev, G Song, B Castillo-Chavez, C TI A simple epidemic model with surprising dynamics SO MATHEMATICAL BIOSCIENCES AND ENGINEERING LA English DT Article DE epidemic model; dynamical system; bifurcation analysis; global stability ID NONLINEAR INCIDENCE RATES; TUBERCULOSIS; TRANSMISSION; BEHAVIOR AB A simple model incorporating demographic and epidemiological processes is explored. Four re-parameterized quantities the basic demographic reproductive number (R-d), the basic epidemiological reproductive number (R-0), the ratio (v) between the average life spans of susceptible and infective class, and the relative fecundity of infectives (theta), are utilized in qualitative analysis. Mathematically, non-analytic vector fields are handled by blow-up transformations to carry out a complete and global dynamical analysis. A family of homoclinics is found, suggesting that a disease outbreak would be ignited by a tiny number of infectious individuals. C1 Howard Univ, Dept Math, Washington, DC 20059 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Montclair State Univ, Dept Mat Sci, Montclair, NJ 07043 USA. Arizona State Univ, Dept Math Sci, Tempe, AZ 85287 USA. RP Berezovsky, F (reprint author), Howard Univ, Dept Math, Washington, DC 20059 USA. EM fsberezo@hotmail.com; karev@ncbi.nlm.nih.gov; songb@mail.montclair.edu; chavez@math.la.asu.edu RI Castillo-Chavez, Carlos/E-1412-2014 OI Castillo-Chavez, Carlos/0000-0002-1046-3901 NR 36 TC 32 Z9 32 U1 0 U2 3 PU AMER INST MATHEMATICAL SCIENCES PI SPRINGFIELD PA PO BOX 2604, SPRINGFIELD, MO 65801-2604 USA SN 1547-1063 J9 MATH BIOSCI ENG JI Math. Biosci. Eng. PD JAN PY 2005 VL 2 IS 1 BP 133 EP 152 PG 20 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 949CM UT WOS:000230762500008 PM 20369916 ER PT J AU McDermott, DH AF McDermott, David H. BE Lotze, MT Thomson, AW TI Cytokine Receptor Heterogeneity SO MEASURING IMMUNITY: BASIC BIOLOGY AND CLINICAL ASSESSMENT LA English DT Article; Book Chapter ID TUMOR-NECROSIS-FACTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 DISEASE PROGRESSION; INTERFERON-GAMMA RECEPTOR; EXPERIMENTAL CEREBRAL MALARIA; CCR5 PROMOTER POLYMORPHISM; PROTEIN-COUPLED RECEPTOR; CORONARY-ARTERY DISEASE; MACROPHAGE-TROPIC HIV-1; SMALL DELETION HOTSPOT C1 NIAID, Mol Signaling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP McDermott, DH (reprint author), NIAID, Mol Signaling Sect, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI McDermott, David/0000-0001-6978-0867 NR 162 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-047933-0 PY 2005 BP 23 EP 34 DI 10.1016/B978-012455900-4/50265-8 PG 12 WC Immunology; Medical Laboratory Technology SC Immunology; Medical Laboratory Technology GA BCN55 UT WOS:000310783900005 ER PT J AU Nares, S Wahl, SM AF Nares, Salvador Wahl, Sharon M. BE Lotze, MT Thomson, AW TI Monocytes and Macrophages SO MEASURING IMMUNITY: BASIC BIOLOGY AND CLINICAL ASSESSMENT LA English DT Article; Book Chapter ID TUMOR-ASSOCIATED MACROPHAGES; INFLAMMATORY-BOWEL-DISEASE; PERIPHERAL-BLOOD MONOCYTES; HEMOGLOBIN SCAVENGER RECEPTOR; LASER CAPTURE MICRODISSECTION; RHEUMATOID-ARTHRITIS PATIENTS; COLONY-STIMULATING FACTOR; NITRIC-OXIDE SYNTHASE; TOLL-LIKE RECEPTORS; GROWTH-FACTOR-BETA C1 [Nares, Salvador; Wahl, Sharon M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Nares, S (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. NR 86 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-047933-0 PY 2005 BP 299 EP 311 DI 10.1016/B978-012455900-4/50287-7 PG 13 WC Immunology; Medical Laboratory Technology SC Immunology; Medical Laboratory Technology GA BCN55 UT WOS:000310783900027 ER PT J AU Panelli, MC Marincola, FM AF Panelli, Monica C. Marincola, Francesco M. BE Lotze, MT Thomson, AW TI Cancer Biometrics SO MEASURING IMMUNITY: BASIC BIOLOGY AND CLINICAL ASSESSMENT LA English DT Article; Book Chapter ID PROSTATE-CANCER; OVARIAN-CANCER; MASS-SPECTROMETRY; HEPATOCELLULAR-CARCINOMA; BIOMARKER DISCOVERY; GEL-ELECTROPHORESIS; PROTEIN MICROARRAYS; PROTEOMIC PATTERNS; RIBOSOME DISPLAY; SERUM BIOMARKER C1 [Panelli, Monica C.; Marincola, Francesco M.] NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Panelli, MC (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 67 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-047933-0 PY 2005 BP 666 EP 696 DI 10.1016/B978-012455900-4/50321-4 PG 31 WC Immunology; Medical Laboratory Technology SC Immunology; Medical Laboratory Technology GA BCN55 UT WOS:000310783900061 ER PT J AU Lee, JW Harrigan, J Opresko, PL Bohr, VA AF Lee, JW Harrigan, J Opresko, PL Bohr, VA TI Pathways and functions of the Werner syndrome protein SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 2nd International Conference on Functional Genomics of Ageing CY APR 28-MAY 01, 2004 CL Hersonissos, GREECE DE base excision repair; telomere; WRN; RecQ conserved; RQC; Werner syndrome ID SYNDROME GENE-PRODUCT; DNA-POLYMERASE-DELTA; SYNDROME HELICASE; SYNDROME CELLS; TELOMERE MAINTENANCE; SYNDROME FIBROBLASTS; MAMMALIAN TELOMERES; REPEAT SEQUENCE; WRN; CLONING AB Mutations in human WRN (also known as RECQ3) gene give rise to a rare autosomal recessive genetic disorder. Werner syndrome (WS). WS is a premature aging disease characterized by predisposition to cancer and early onset of symptoms related to normal aging including osteoporosis, ocular cataracts, graying and loss of hair, diabetes mellitus. arteriosclerosis, and atherosclerosis. This review focuses on the functional role of Werner protein (WRN) in guarding the genetic stability of cells, particularly by playing an integral role in the, base excision repair, and at the telomere ends. Furthermore. in-depth biochemical investigations have significantly advanced our understanding of WRN protein regarding its binding partners and the site of protein-protein interaction. The mapping analysis of protein interaction sites in WRN for most of its binding partners have revealed a common site of protein-protein interaction in the RecQ conserved (RQC) region of WRN. Published by Elsevier Ireland Ltd. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov OI Opresko, Patricia/0000-0002-6470-2189 NR 86 TC 67 Z9 67 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2005 VL 126 IS 1 SI SI BP 79 EP 86 DI 10.1016/j.mad.2004.09.011 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 891EL UT WOS:000226564000011 PM 15610765 ER PT J AU Hsu, HC Li, LN Zhang, HG Mountz, JD AF Hsu, HC Li, LN Zhang, HG Mountz, JD TI Genetic regulation of thymic involution SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 2nd International Conference on Functional Genomics of Ageing CY APR 28-MAY 01, 2004 CL Hersonissos, GREECE DE thymic involution; genetics; BXD RI mice; IL-12; proteomics; tumor ID AGE-RELATED-CHANGES; MOUSE STRAINS; AGING MICE; T-CELLS; LOCI; SUSCEPTIBILITY; RECEPTOR; IL-12; ATHEROSCLEROSIS; PEROXIREDOXINS AB In this review, we have summarized our work using combined complex statistical genetics, bioinformatics, and functional genomics to determine the genetic basis of the age-related thymic involution in C57BU6J X DBA/2J recombinant inbred mice and the parental B6 and D2 mice. We have shown that these mice provided a valuable genetic model that can permit resampling of thymuses from different aged but genetically identical animals and determination of the relative significance of age-associated changes in the thymus. Our results suggest that the quantitative trait loci (QTL) regulating the Con A-induced thymocyte proliferative response were mapped to mouse. chromosome Chr 11 (D11Mit51 at 18 cM), a region that harbors the IL-12b gene. The importance of IL-12b in maintaining thymic integrity and function during the aging process was confirmed by a more rapid involution of the thymus in IL-12b knockout (IL-12b(-/-)) mice compared to wild-type (WT) mice. Functionally, IL-12 provided a strong synergistic effect to augment the IL-7 or IL-2 induced thymocyte proliferative response. especially in both aged WT and IL-12b(-/-) mice, but not in normal young mice. In contract to the proliferative response, the age-related decline in the total number of thymocytes was determined at different age, and mapped to loci on Chr 9, 62 cM and Chr 10, 32 cM. Using matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS), increased expression of peroxiredoxin was found to be correlated with thymic involution. Our results suggest the possibility to identify the complex molecular network that can be associated with the regulation of thymic involution in aged mice using a high-dimensional functional genomics approach. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. NHLBI, NIH, LBG, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Birmingham, AL 35233 USA. RP Mountz, JD (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, 701 S 19th St,LHRB 473, Birmingham, AL 35294 USA. EM john.mountz@ccc.uab.edu FU NIA NIH HHS [R01 AG 16653]; NIAID NIH HHS [R01 AI46990] NR 51 TC 19 Z9 21 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JAN PY 2005 VL 126 IS 1 SI SI BP 87 EP 97 DI 10.1016/j.mad.2004.09.016 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 891EL UT WOS:000226564000012 PM 15610766 ER PT J AU Hawk, ET Umar, A Richmond, E Viner, JL AF Hawk, ET Umar, A Richmond, E Viner, JL TI Prevention and therapy of colorectal cancer SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; ELEVATED CYCLOOXYGENASE-2 EXPRESSION; FLUOROURACIL PLUS LEUCOVORIN; RANDOMIZED CONTROLLED-TRIAL; HIGH-DOSE LEUCOVORIN; ESTROGEN REPLACEMENT THERAPY; SURGICAL ADJUVANT BREAST; B2 COLON-CANCER; RECTAL-CANCER; CONTINUOUS-INFUSION AB Colorectal cancer (CRC) accounts for about 10% of cancer mortality in the United States, causing 57,000 deaths in 2004 alone [1]. Approximately 146,000 new cases of CRC are diagnosed each year: 106,000 in the colon and the remainder in the rectum. Mortality has been declining steadily since the 1980s, most likely because of early CRC detection and intervention against early stage disease, including adenomas. Although growing knowledge of disease pathogenesis and the emergence of various screening tools and early medical and surgical interventions have made CRC one of the most preventable of all cancers, it remains the second leading cause of cancer mortality in the United States. This article focuses on established and promising classes of agents developed for CRC prevention and treatment. C1 NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Bethesda, MD 20892 USA. RP Hawk, ET (reprint author), NCI, Gastrointestinal & Other Canc Res Grp, Div Canc Prevent, EPN, Suite 2141,6130 Execut Blvd, Bethesda, MD 20892 USA. EM eh51p@nih.gov NR 137 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2005 VL 89 IS 1 BP 85 EP + DI 10.1016/j.mcna.2004.08.003 PG 27 WC Medicine, General & Internal SC General & Internal Medicine GA 874RX UT WOS:000225368600005 PM 15527810 ER PT J AU Nakamura, M Chen, Q Sugi, T Ikeda, A Shibasaki, H AF Nakamura, M Chen, Q Sugi, T Ikeda, A Shibasaki, H TI Technical quality evaluation of EEG recording based on electroencephalographers' knowledge SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE technical quality evaluation; EEG recording; technical artifact; physiological status; assistant tool ID AUTOMATIC INTEGRATIVE INTERPRETATION; AWAKE BACKGROUND EEG; ARTIFACTS; SLEEP AB The aim of this study is to develop a technical quality evaluation system of electroencephalogram (EEG) recording in order to acquire technically satisfactory EEG records, which may contribute to the accuracy improvement of EEG interpretation. In our developed system, the evaluation of EEG recording comprises the detection of technical artifacts and physiological status, which indicates the recording status objectively. In addition, the caution signals to users are generated in the system according to the undesired status detected. The information displayed to users includes the updated EEG records and instant evaluation results. Two examples of evaluation results are introduced in this paper, illustrating unsatisfactory records and artifact free records, respectively. The experimental results are proposed to verify the effectiveness of the technical quality evaluation of EEG recording. The implementation of the technical quality evaluation of EEG recording is helpful to acquire technically satisfactory EEG records, which may improve the accuracy of results in both the visual and the automatic EEG interpretation, and ease the laborious work of EEG technicians in the recording progress. (C) 2004 IPEM. Published by Elsevier Ltd. All rights reserved. C1 Saga Univ, Dept Adv Syst Control Engn, Grad Sch Sci & Engn, Saga 8408502, Japan. Saga Univ, Dept Elect & Elect Engn, Fac Sci & Engn, Saga 8408502, Japan. Kyoto Univ, Dept Neurol, Grad Sch Med, Kyoto 6068507, Japan. NIH, Bethesda, MD 20892 USA. RP Nakamura, M (reprint author), Saga Univ, Dept Adv Syst Control Engn, Grad Sch Sci & Engn, Saga 8408502, Japan. EM nakamura@cntl.ee.saga-u.ac.jp OI Ikeda, Akio/0000-0002-0790-2598 NR 14 TC 13 Z9 15 U1 3 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD JAN PY 2005 VL 27 IS 1 BP 93 EP 100 DI 10.1016/j.medengphy.2004.09.001 PG 8 WC Engineering, Biomedical SC Engineering GA 889KY UT WOS:000226443100012 PM 15604010 ER PT J AU Blanco, IE de Serres, FJ Fernandez-Bustillo, E Al Kassam, D Arbesu, D Rodriguez, C Torre, JC AF Blanco, IE de Serres, FJ Fernandez-Bustillo, E Al Kassam, D Arbesu, D Rodriguez, C Torre, JC TI alpha 1-Antitrypsin and fibromyalgia: new data in favour of the inflammatory hypothesis of fibromyalgia SO MEDICAL HYPOTHESES LA English DT Article ID ALPHA(1)-ANTITRYPSIN DEFICIENCY; PROTEASE INHIBITORS; FATIGUE SYNDROME; APOPTOTIC CELLS; SKELETAL-MUSCLE; MAST-CELLS; CYTOKINES; ENTEROVIRUS; PREVALENCE; PATHOLOGY AB alpha 1-Antitrypsin (AAT) circulates in high serum concentrations, and impregnates most body tissues. AAT has a broad anti-inflammatory spectrum, and modulates most inflammatory reactions occurring in human body. Recently, a possible relationship between AAT deficiency (AAT-D) and fibromyalgia (FM) has been raised, with the finding that intravenous infusions of purified human AAT efficiently controlled FM symptoms in two patients with severe hereditary AAT-D. On the other hand, functional magnetic resonance imaging has detected a significant greater activity in pain sensitive areas of the brain in patients with FM, in response to cutaneous stimuli, providing further evidence for a physiological explanation for FM pain. In recent studies abnormal profiles of inflammation markers in serum and biopsies have been found in FM patients. Since most of these inflammation mediators can be inhibited by AAT, these observations would suggest that at least a subset of the FM syndrome could be related to an inflammatory process, possibly due to an imbalance between inflammatory and anti-inflammatory substances, in the soft body tissues. Future directions of research would be: (1) to develop epidemiological studies to determine the gene frequency of AAT deficiency alleles in FM patients; (2) implementation of a double-blind placebo-controlled clinical trial to determine the specific role of AAT augmentation therapy in AAT-D patients with FM; (3) identification of specific laboratory markers for diagnostic and clinical evaluation purposes in FM; (4) application of the newest medical imaging techniques for diagnosis; and (5) identification of genetic, familial, and environmental risk factors suspected to participate in the FM syndrome development. (c) 2004 Elsevier Ltd. All rights reserved. C1 Hosp Valle Nalon, Dept Internal Med, Riano Langreo 33920, Principado Astr, Spain. NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Hosp Univ Cent Asturias, Biostat Unit, Oviedo 33006, Principado Astu, Spain. Hosp Valle Nalon, Dept Clin Biochem, Riano Langreo 33920, Principado Astr, Spain. Hosp Valle Nalon, Dept Rehabil, Riano Langreo 33920, Principado Astr, Spain. Hosp Univ Cent Asturias, Inst Nacl Silicosis, Dept Clin Biochem, Oviedo 33006, Principado Astu, Spain. Hosp Univ Cent Asturias, Hosp Monte Naranco, Dept Rheumatol, Oviedo 33006, Principado Astu, Spain. RP Blanco, IE (reprint author), Hosp Valle Nalon, Dept Internal Med, Riano Langreo 33920, Principado Astr, Spain. EM ignacio.blanco@sespa.princast.es NR 57 TC 18 Z9 21 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 EI 1532-2777 J9 MED HYPOTHESES JI Med. Hypotheses PY 2005 VL 64 IS 4 BP 759 EP 769 DI 10.1016/j.mehy.2004.10.005 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 906SP UT WOS:000227663500015 PM 15694694 ER PT S AU Petrick, N Gallas, BD Samuelson, FW Wagner, RF Myers, KJ AF Petrick, N Gallas, BD Samuelson, FW Wagner, RF Myers, KJ BE Eckstein, MP Jiang, Y TI Influence of panel size and expert skill on truth panel performance when combining expert ratings SO Medical Imaging 2005: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE panel truth; expert panel; observer study; Monte Carlo simulations; ideal observer; computer-aided diagnosis; receiver-operating characteristic curve AB The focus of this manuscript is to investigate the statistical properties of expert panels used as a substitute for clinical truth through a simplistic Monte Carlo simulation model. We use Gaussian models to simulate both normal and abnormal distributions of ideal-observer test statistics. These distributions are designed to produce an ideal observer area under the ROC curve (AUC) of 0.85. Expert observers are modeled as an ideal observer test statistic degraded by a zero-mean Gaussian random variable. Different expert skill levels are achieved by changing the added variance. The experts' skill ranges between 0.6 and 0.8 in AUC. We combine decisions from 2-10 experts into a panel score by taking the median of all expert ratings as the panel test statistic. In experiment 1, truth panels made up of 2, 4, 8 and 10 experts who had the same skill level (AUC = 0.8) achieved mean AUCs of 0.82, 0.83, 0.84, and 0.84, respectively. For experiment 2, the experts' skill level was varied uniformly between 0.6 and 0.8 in AUC. Panel performance decreased in experiment 2 compared to the fixed skill level panels in experiment 1. However, panels composed of 8 and 10 experts still achieved an AUC greater than 0.80, the maximum of any individual expert. These simulation experiments, while idealized and simplistic, are a starting point for understanding the implications of using a panel of experts as surrogate truth in ROC studies when a gold standard is not available. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Petrick, N (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5723-X J9 P SOC PHOTO-OPT INS PY 2005 VL 5749 BP 49 EP 57 DI 10.1117/12.596286 PG 9 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCF61 UT WOS:000229068500007 ER PT S AU Kyprianou, IS Ganguly, A Rudin, S Bednarek, DR Gallas, BD Myers, KJ AF Kyprianou, IS Ganguly, A Rudin, S Bednarek, DR Gallas, BD Myers, KJ BE Eckstein, MP Jiang, Y TI Efficiency of the human observer compared to an ideal observer based on a generalized NEQ which incorporates scatter and geometric unsharpness: Evaluation with a 2AFC experiment SO MEDICAL IMAGING 2005: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE MTF; NPS; NEQ; DQE; SNR; system; generalized; detectability; observer; angiography; microrangiography ID BASIC IMAGING PROPERTIES; MODULATION TRANSFER-FUNCTION; DIGITAL RADIOGRAPHY; MICRO-ANGIOGRAPHY; MAMMOGRAPHY; QUALITY; INFORMATION; PERFORMANCE; REDUCTION; CONTRAST AB Under certain assumptions the detectability of the ideal observer can be defined as the integral of the system Noise Equivalent Quanta multiplied by the squared object spatial frequency distribution. Using the detector Noise-EquivalentQuanta (NEQ(D)) for the calculation of detectability inadequately describes the performance of an x-ray imaging system because it does not take into account the effects of patient scatter and geometric unsharpness. As a result, the ideal detectability index is overestimated, and hence the efficiency of the human observer in detecting objects is underestimated. We define a Generalized-NEQ (GNEQ) for an x-ray system referenced at the object plane that incorporates the scatter fraction, the spatial distributions of scatter and focal spot, the detector MTFD, and the detector Normalized-Noise-Power-Spectrum (NNPSD). This GNEQ was used in the definition of the ideal detectability for the evaluation of the human observer efficiency during a two Alternative Forced Choice (2-AFC) experiment, and was compared with the case where only the NEQ(D) was used in the detectability calculations. The 2-AFC experiment involved the detection of images of polyethylene tubes (diameters between 100-300 mu m) filled with iodine contrast (concentrations between 0-120 Mg/cm(3)) placed onto a uniform head equivalent phantom placed near the surface of a microangiographic detector (43 mu m pixel size). The resulting efficiency of the human observer without regarding the effects of scatter and geometric unsharpness was 30%. When these effects were considered the efficiency was increased to 70%. The ideal observer with the GNEQ can be a simple optimization method of a complete imaging system. C1 US FDA, CDER, NIBIB, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP US FDA, CDER, NIBIB, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy HFZ 140, Rockville, MD 20852 USA. EM iacovos.kyprianou@fda.hhs.gov FU NIBIB NIH HHS [R01 EB002873-03, R01 EB002873-01, R01 EB002873-02, R01 EB002873-04, R01 EB002873]; NINDS NIH HHS [R01 NS038746, R01 NS038746-02, R01 NS038746-01, R01 NS038746-03] NR 47 TC 6 Z9 6 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5723-X J9 PROC SPIE PY 2005 VL 5749 BP 251 EP 262 DI 10.1117/12.595870 PG 12 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCF61 UT WOS:000229068500028 PM 21311735 ER PT S AU Rohde, GK Barnett, AS Basser, PJ Pierpaoli, C AF Rohde, GK Barnett, AS Basser, PJ Pierpaoli, C BE Fitzpatrick, JM Reinhardt, JM TI Estimating intensity variance due to noise in registered images SO Medical Imaging 2005: Image Processing, Pt 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE image registration; interpolation; variance; noise; parameter estimation ID APPARENT DIFFUSION-COEFFICIENT; ECHO-PLANAR IMAGES; FMRI TIME-SERIES; MR-IMAGES; HUMAN BRAIN; INTERPOLATION; DISTORTION; TENSOR; REGISTRATION; ARTIFACTS AB Image registration refers to the process of finding the spatial correspondence between two or more images. This is usually done by applying a spatial transformation, computed automatic or manually, to a given image using a continuous image model computed either with interpolation or approximation methods. We show that noise induced signal variance in interpolated images differs significantly from the signal variance of the original images in native space. We describe a simple approach to compute the signal variance in registered images based on the signal variance and covariance of the original images, the spatial transformations computed by the registration procedure, and the interpolation or approximation kernel chosen. Our approach is applied to diffusion tensor (DT) MRI data. We show that incorrect noise variance estimates in registered diffusion weighted images can affect the estimated DT parameters, their estimated uncertainty, as well as indices of goodness of fit such as chi-square maps. In addition to DT-MRI, we believe that this methodology would be useful any time parameter extraction methods are applied to registered or interpolated data. C1 NICHD, LIMB, STBB, NIH, Bethesda, MD 20892 USA. RP Rohde, GK (reprint author), NICHD, LIMB, STBB, NIH, Bethesda, MD 20892 USA. NR 30 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5721-3 J9 P SOC PHOTO-OPT INS PY 2005 VL 5747 BP 655 EP 666 DI 10.1117/12.593635 PN 1-3 PG 12 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCN01 UT WOS:000230109600066 ER PT S AU Chang, LC Rohde, GK Pierpaoli, C AF Chang, LC Rohde, GK Pierpaoli, C BE Fitzpatrick, JM Reinhardt, JM TI An automatic method for estimating noise-induced signal variance in magnitude-reconstructed magnetic resonance images SO Medical Imaging 2005: Image Processing, Pt 1-3 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE signal variance; noise variance; magnitude-reconstructed MRI; density estimation ID MR-IMAGES AB Signal intensity in magnetic resonance images (MRIs) is affected by random noise. Assessing noise-induced signal variance is important for controlling image quality. Knowledge of signal variance is required for correctly computing the chi-square value, a measure of goodness of fit, when fitting signal data to estimate quantitative parameters such as T1 and T2 relaxation times or diffusion tensor elements. Signal variance can be estimated from measurements of the noise variance in an object- and ghost-free region of the image background. However, identifying a large homogeneous region automatically is problematic. In this paper. a novel, fully automated approach for estimating the noise-induced signal variance in magnitude-reconstructed MRIs is proposed. This approach is based on the histogram analysis of the image signal intensity, explicitly by extracting the peak of the underlining Rayleigh distribution that would characterize the distribution of the back-round noise. The peak is extracted using a nonparametric univariate density estimation like the Parzen window density estimation-, the corresponding peak position is shown here to be the expected signal variance in the object. The proposed method does not depend on prior fore-round segmentation, and only one image with a small amount of back-round is required when the signal-to-noise ratio (SNR) is greater than three. This method is applicable to magnitude-reconstructed MRIs, though diffusion tensor (DT)-MRI is used here to demonstrate the approach. C1 NICHD, NIH, Bethesda, MD USA. RP Chang, LC (reprint author), NICHD, NIH, Bethesda, MD USA. NR 10 TC 15 Z9 15 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5721-3 J9 P SOC PHOTO-OPT INS PY 2005 VL 5747 BP 1136 EP 1142 DI 10.1117/12.596008 PN 1-3 PG 7 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCN01 UT WOS:000230109601047 ER PT S AU Yao, JH Zujewski, JA Orzano, J Prindiville, S Chow, C AF Yao, JH Zujewski, JA Orzano, J Prindiville, S Chow, C BE Fitzpatrick, JM Reinhardt, JM TI Classification and calculation of breast fibroglandular tissue volume on SPGR fat suppressed MRI SO MEDICAL IMAGING 2005: IMAGE PROCESSING, PT 1-3 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE breast segmentation; tissue classification; SPGR fat suppressed MRI; fibroglandular AB This paper presents an automatic method to classify and quantify breast fibroglandular tissues on T1 weighted spoiled gradient-echo (SPGR) fat suppressed MRI. The breast region is segmented from the image using mathematical morphology, region growing, and active contour models. The breast-air and breast-chest wall boundaries are located using smooth and continuous curves. Three tissue types are defined: fatty tissue, fibroglandular tissue, and skin. We then employ a fuzzy C-means (FCM) method for tissue classification. For each pixel inside the breast region, the normalized pixel intensity and normalized distance to the breast-air boundary are computed. These two values form a two-dimensional feature space. A fuzzy class is defined for each tissue type. The initial centroid for each class is obtained from training images. The pixel membership values indicate the possibility of a pixel belonging to a certain tissue class. Pixels with highest membership in the fibroglandular class are then classified as fibroglandular tissue. We have tested our method on 29 patients. We automatically segmented the breasts and computed the volume percentage of fibroglandular tissue for both left and right breasts. We then compared the calculated tissue classification with manually generated tissue classification by two experienced radiologists. The two results agreed on 94.95% of breast segmentation, and the average fibroglandular percentage difference is about 3%. This method is useful in research studies assessing breast cancer risk. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 12 TC 15 Z9 15 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5721-3 J9 PROC SPIE PY 2005 VL 5747 BP 1942 EP 1949 DI 10.1117/12.594671 PN 1-3 PG 8 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCN01 UT WOS:000230109602052 ER PT S AU Antani, S Natarajan, M Long, JL Long, LR Thoma, GR AF Antani, S Natarajan, M Long, JL Long, LR Thoma, GR BE Ratib, OM Horii, SC TI Developing a comprehensive system for content-based retrieval of image and text data from a national survey SO Medical Imaging 2005: PACS and Imaging Informatics SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE content-based image retrieval (CBIR); NHANES II; anterior osteophytes; medical image databases; medical image informatics; image segmentation; shape similarity; procrustes distance; Fourier descriptors; polygon approximation ID CURVES AB The article describes the status of our ongoing R&D at the U.S. National Library of Medicine (NLM) towards the development of an advanced multimedia database biomedical information system that supports content-based image retrieval (CBIR). NLM maintains a collection of 17,000 digitized spinal X-rays along with text survey data from the Second National Health and Nutritional Examination Survey (NHANES II). These data serve as a rich data source for epidemiologists and researchers of osteoarthritis and musculoskeletal diseases. It is currently possible to access these through text keyword queries using our Web-based Medical Information Retrieval System (WebMIRS). CBIR methods developed specifically for biomedical images could offer direct visual searching of these images by means of example image or user sketch. We are building a system which supports hybrid queries that have text and image-content components. R&D goals include developing algorithms for robust image segmentation for localizing and identifying relevant anatomy, labeling the segmented anatomy based on its pathology, developing suitable indexing and similarity matching methods for images and image features, and associating the survey text information for query and retrieval along with the image data. Some highlights of the system developed in MATLAB and Java are: use of a networked or local centralized database for text and image data; flexibility to incorporate new research work; provides a means to control access to system components under development; and use of XML for structured reporting. The article details the design, features, and algorithms in this third revision of this prototype system, CBIR3. C1 NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, DHHS, Bethesda, MD 20894 USA. RP Antani, S (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, DHHS, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 16 TC 2 Z9 2 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5722-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5748 BP 152 EP 161 DI 10.1117/12.596587 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BCF60 UT WOS:000229065900018 ER PT S AU Badano, A Sempau, J Jennings, RJ AF Badano, A Sempau, J Jennings, RJ BE Flynn, MJ TI Statistics of the scintillation output using a combined x-ray/electron/optical Monte Carlo method SO Medical Imaging 2005: Physics of Medical Imaging, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE columnar phosphor; pulse-height distribution; swank factor; detective quantum efficiency; Monte Carlo simulation; cesium iodide AB Simulations of digital imaging systems based on scintillator screens usually employ a Poisson model for the phosphor conversion gain. However, the statistics of the scintillation output are determined by complex phenomena that involve many sources of variability including inhomogeneities in the crystalline and screen structure, variations in the deposited energy for each primary quantum available for excitation, variations in the relationship between radiate and non-radiative decay processes, energy dependencies in the conversion gain variance, and spread of secondary quanta. We use a combined x-ray/electron/optical Monte Carlo code to study the statistics of the scintillation output in columnar phosphors. The simulation code is the result of merging the x-ray transport code PENELOPE and the optical transport code DETECT-II. Using an improved geometric model for the columnar structure, we present results concerning pulse-height spectra of the scintillation output (and corresponding Swank factors) as a function of x-ray energy. This study improves our understanding of the underlying causes of conversion gain variations and should facilitate more accurate simulation efforts for the investigation and optimization of image acquisition systems based on scintillator screens. C1 US FDA, Ctr Devices & Radiol Hlth, NIBIB,Div Imaging & Appl Math, Lab Assessment Med Imaging Syst,Off Sci & Engn La, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, NIBIB,Div Imaging & Appl Math, Lab Assessment Med Imaging Syst,Off Sci & Engn La, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 3 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5719-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5745 BP 361 EP 365 DI 10.1117/12.596724 PN 1-2 PG 5 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BCL61 UT WOS:000229929500039 ER PT S AU Hsu, LY Kellman, P Natanzon, A Hirsch, GA Aletras, AH Arai, AE AF Hsu, LY Kellman, P Natanzon, A Hirsch, GA Aletras, AH Arai, AE BE Amini, AA Manduca, A TI Computerized measurement of myocardial infarct size on contrast-enhanced magnetic resonance images SO Medical Imaging 2005: Physiology, Function, and Structure From Medical Images, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE myocardial infarction; magnetic resonance imaging; computer quantification ID IRREVERSIBLE INJURY; VIABILITY AB Purpose: To validate a computer algorithm for measuring myocardial infarct size on gadolinium enhanced MR images. The results of computer infarct sizing are studied on phase-sensitive and magnitude imaging against a histopathology reference. Materials and Methods: Validations were performed in 9 canine myocardial infarctions determined by triphenyltetrazolium chloride (TTC). The algorithm analyzed the pixel intensity distribution within manually traced myocardial regions. Pixels darker than an automatically determined threshold were first excluded from further analysis. Selected image features were used to remove false positive regions. A threshold 50% between bright and dark regions was then used to minimize partial volume errors. Post-processing steps were applied to identify microvascular obstruction. Both phase sensitive and magnitude reconstructed MR images were measured by the computer algorithm in units of % of the left ventricle (LV) infarction and compared to TTC. Results: Correlations of MR and TTC infarct size were 0.96 for both phase sensitive and magnitude imaging. Bland Altman analysis showed no consistent bias as a function of infarct size. The average error of computer infarct sizing was less than 2% of the LV for both reconstructions. Fixed intensity thresholding was less accurate compared to the computer algorithm. Conclusions: MR can accurately depict myocardial infarction. The proposed computer algorithm accurately measures infarct size on contrast-enhanced MR images against the histopathology reference. It is effective for both phase-sensitive and magnitude imaging. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Hsu, LY (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Aletras, Anthony/0000-0002-3786-3817 NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5720-5 J9 P SOC PHOTO-OPT INS PY 2005 VL 5746 BP 168 EP 174 DI 10.1117/12.595371 PN 1-2 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BCH30 UT WOS:000229312100020 ER PT S AU Yao, JH Summers, RM Hara, A AF Yao, JH Summers, RM Hara, A BE Amini, AA Manduca, A TI Optimizing the support vector machines (SVM) committee configuration in a colonic polyp CAD system SO Medical Imaging 2005: Physiology, Function, and Structure From Medical Images, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE Computer Aided Detection; committee of Support Vector Machines; CT colonography; two-way ANOVA AB This paper presents a method to optimize the SVM committee used in a colonic polyp CAD system to achieve high detection performance and efficiency. In our CAD system, characteristic features of polyp candidates are fed into a committee of SVMs to determine if one detection is a true polyp. The committee consists of M different SVMs, and each of them is established by an N-feature vector. A progressive feature vector selection scheme was proposed to select a population of feature vectors, in which N-feature vectors are composed progressively in N stages. To optimize the SVM committee configuration, two-way ANOVA is performed to analyze the effect of committee-member-number (M) and feature-vector-length (N). The area under the ROC curve (AUC) in a ten-fold cross validation is used as the performance metric. Pairwise Tukey's tests are performed to reveal if the performance differences between two configurations are statistically significant. The experiments were tested on 29 patients with 53 polyps. The committee configuration in comparison are N = 1 to 7 and M = 1, 3, 5, 7, or 9. ANOVA showed that N = 3 has statistically significant performance improvement over N = 1 and 2, but is statistically equivalent with N = 4 to 7. It also showed that there is statistical improvement from M = 1 to 7, while M = 7 and 9 are statistically equivalent. Based on the result, we chose a committee configuration with N = 3 and M = 7 since it is the most efficient committee with statistically best performance. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5720-5 J9 P SOC PHOTO-OPT INS PY 2005 VL 5746 BP 384 EP 392 DI 10.1117/12.594547 PN 1-2 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BCH30 UT WOS:000229312100041 ER PT S AU Huang, A Summers, RM Hara, AK AF Huang, A Summers, RM Hara, AK BE Amini, AA Manduca, A TI Surface curvature estimation for automatic colonic polyp detection SO Medical Imaging 2005: Physiology, Function, and Structure From Medical Images, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE CT colonography; virtual colonoscopy; computer-aided diagnosis; curvature estimation; surface fitting; volume data; polyp detection ID IMAGES AB Colonic polyps are growths on the inner wall of the colon. They appear like elliptical protrusions which can be detected by curvature-derived shape discriminators. For reasons of computation efficiency, much of the past work in computer-aided diagnostic CT colonography adopted kernel-based convolution methods in curvature estimation. However, kernel methods can yield erroneous results at thin structures where the gradient diminishes. In this paper, we investigate three surface patch fitting methods: Cubic B-spline, paraboloid, and quadratic polynomials. This '' patch '' approach is based on the fact that a surface can be re-oriented such that it can be approximated by a bivariate function locally. These patch methods are evaluated by synthesized data with various orientations and sampling sizes. We find that the cubic spline method performs best regardless of large orientation variances. Cubic spline and quadratic polynomial methods perform equally well for large samples while the latter performs better for small ones. Based on the performance evaluation, we propose a new, two-stage curvature estimation method. The cubic spline fitting is performed first for its insensitivity to orientation. If the spline fitting errs by more than a preset value (indicating high surface tortuosity), a small data sample is fitted by a quadratic function. The evaluation is performed on 29 patients (58 data sets). With 88.7% sensitivity, the average number of false positives per data set is reduced by 44.5% from 33.5 (kernel method) to 18.6 (new method). C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Huang, A (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 17 TC 30 Z9 30 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5720-5 J9 P SOC PHOTO-OPT INS PY 2005 VL 5746 BP 393 EP 402 DI 10.1117/12.594644 PN 1-2 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BCH30 UT WOS:000229312100042 ER PT S AU Bitter, I Aslam, B Huang, A Summers, RM AF Bitter, I Aslam, B Huang, A Summers, RM BE Amini, AA Manduca, A TI Candidate determination for computer aided detection of colon polyps SO Medical Imaging 2005: Physiology, Function, and Structure From Medical Images, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE computer aided detection; colon polyp candidate; water-plane method; polyp segmentation; virtual colonoscopy AB Given a segmented CT scan data of the colon represented as a triangle mesh, our water-plane algorithm will detect polyp candidates. The water-plane method comprises of pouring water into a polyp protrusion from the outside of the colon and in raising the "water-plane" until it cannot be incremented. any further without causing water leakage. The method starts at a vertex and uses average normal of all triangles adjacent to the starting vertex to generate the initial water-plane, which will make the starting vertex "wet" but leave its neighboring vertices "dry". The method will continue to wet neighboring vertices one by one and then their neighbors and so on until the water-plane cannot move any further without causing water leakage. The water-plane movement alternates between just raising the water level in completely convex regions and tilting about one or two anchor vertices that have neighbors that would get wet if the water level was raised any more. The final set of wet vertices is a cluster that is an initial polyp candidate. The water-plane method was compared against the current polyp candidate detection method in our Computer Aided Detection of Colon Polyps software pipeline, called the surface curvature method. It finds clusters of connected vertices that all exhibit elliptical curvature. The water-plane method showed multiple improvements in polyp candidate detection. It detected polyp candidates missed by the surface curvature method. It exhibited continuous polyp candidate regions instead of non-uniform or incomplete regions detected by the surface curvature method. And finally, it avoided some false positive detections reported by surface curvature method. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20895 USA. RP Bitter, I (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20895 USA. NR 1 TC 2 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5720-5 J9 P SOC PHOTO-OPT INS PY 2005 VL 5746 BP 804 EP 809 DI 10.1117/12.595667 PN 1-2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BCH30 UT WOS:000229312100085 ER PT S AU Gutierrez, LF Shechter, G Lederman, RJ McVeigh, ER Ozturk, C AF Gutierrez, LF Shechter, G Lederman, RJ McVeigh, ER Ozturk, C BE Galloway, RL Cleary, KR TI Distortion correction, calibration, and registration: Towards an integrated MR and X-ray interventional suite SO MEDICAL IMAGING 2005: VISUALIZATION, IMAGE-GUIDED PROCEDURES, AND DISPLAY, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE MRI; X-ray angiography; XMR; image-guided surgery; image registration; 2D-3D registration; cardiovascular intervention ID IMAGES; TRACKING AB We present our co-registration results of two complementary imaging modalities, MRI and X-ray angiography (XA), using dual modality fiducial markers. Validation experiments were conducted using a vascular phantom with eight fiducial markers around its periphery. Gradient-distortion-corrected 3D MRI was used to image the phantom and determine the 3D locations of the markers. XA imaging was performed at various C-arm orientations. These images were corrected for geometric distortion, and projection parameters were optimized using a calibration phantom. Closed-form 3D-to-3D rigid-body registration was performed between the MR markers and a 3D reconstruction of the markers from multiple XA images. 3D-to-2D registration was performed using a single XA image by projecting the MR markers onto the XA image and iteratively minimizing the 2D errors between the projected markers and their observed locations in the image. The RMS registration error was 0.77 mm for the 3D-to-3D registration, and 1.53 pixels for the 3D-to-2D registration. We also showed that registration can be performed at a large IS where many markers are visible, then the image can be zoomed in maintaining the registration. This requires calibration of imperfections in the zoom operation of the image intensifier. When we applied the registration used for an IS of 330 mm to an image acquired with an IS of 130 mm, the error was 42.16 pixels before zoom correction and 3.37 pixels after. This method offers the possibility of new therapies where the soft-tissue contrast of MRI and the high-resolution imaging of XA are both needed. C1 Natl Heart Lung & Blood Inst, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Natl Heart Lung & Blood Inst, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM GutierrezLF@nih.gov RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 NR 12 TC 8 Z9 8 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5718-3 J9 PROC SPIE PY 2005 VL 5744 BP 146 EP 156 DI 10.1117/12.597823 PN 1-2 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BCH33 UT WOS:000229312400016 ER PT J AU Shechter, G Resar, JR McVeigh, ER AF Shechter, G Resar, JR McVeigh, ER TI Rest period duration of the coronary arteries: Implications for magnetic resonance coronary angiography SO MEDICAL PHYSICS LA English DT Article DE heart; respiration; motion artifacts ID RESPIRATORY MOTION; MR-ANGIOGRAPHY; CARDIAC MOTION; HEART; LUMEN AB Magnetic resonance (MR) and computed tomography coronary imaging is susceptible to artifacts caused by motion of the heart. The presence of rest periods during the cardiac and respiratory cycles suggests that images free of motion artifacts could be acquired. In this paper, we studied the rest period (RP) duration of the coronary arteries during a cardiac contraction and a tidal respiratory cycle. We also studied whether three MR motion correction methods could be used to increase the respiratory RP duration. Free breathing x-ray coronary angiograms were acquired in ten patients. The three-dimensional (3D) structure of the coronary arteries was reconstructed from a biplane acquisition using stereo reconstruction methods. The 3D motion of the arterial model was then recovered using an automatic motion tracking algorithm. The motion field was then decomposed into separate cardiac and respiratory components using a cardiac respiratory parametric model. For the proximal-to-middle segments of the right coronary artery (RCA), a cardiac RP (<1 mm 3D displacement) of 76 34 ins was measured at end systole (ES), and 65 42 ms in mid-diastole (MD). The cardiac RP was 80 25 ms at ES and 112 42 ins at MD for the proximal 5 cm of the left coronary tree. At end expiration, the respiratory RP (in percent of the respiratory period) was 26 +/- 8% for the RCA and 27 +/- 17% for the left coronary tree. Left coronary respiratory RP (<0.5 mm 3D displacement) increased with translation (32% of the respiratory period), rigid body (51%), and affine (79%) motion correction. The RCA respiratory RP using translational (27%) and rigid body (33%) motion correction were not statistically different from each other. Measurements of the cardiac and respiratory rest periods will improve our understanding of the temporal and spatial resolution constraints for coronary imaging. (C) 2005 American Association of Physicists in Medicine. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. RP Shechter, G (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1D-412,Msc 1061, Bethesda, MD 20892 USA. EM shechter@bme.jhu.edu FU Intramural NIH HHS [Z01 HL004608-08] NR 23 TC 21 Z9 21 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2005 VL 32 IS 1 BP 255 EP 262 DI 10.1118/1.1836291 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 891QM UT WOS:000226595600030 PM 15719976 ER PT J AU Laughlin, MR Rothman, DL Shulman, RG AF Laughlin, Maren R. Rothman, Douglas L. Shulman, Robert G. BE Shulman, RG Rothman, DL TI C-13 NMR Studies of Heart Glycogen Metabolism SO METABOLOMICS BY IN VIVO NMR LA English DT Article; Book Chapter ID NUCLEAR-MAGNETIC-RESONANCE; WORKING RAT HEARTS; GLUCOSE-METABOLISM; IN-VIVO; PERFUSED HEARTS; GLYCOLYSIS; INSULIN; STIMULATION; ISCHEMIA; INVIVO C1 [Laughlin, Maren R.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Rothman, Douglas L.] Yale Univ, Sch Med, MR Ctr, Dept Diagnost Radiol, New Haven, CT 06520 USA. RP Laughlin, MR (reprint author), NIDDKD, NIH, 6707 Democracy Blvd,Room 6101,MSC 5460, Bethesda, MD 20892 USA. EM laughlinm@extra.niddk.nih.gov; douglas.rothman@yale.edu; robert.shulman@yale.edu; robert.shulman@yale.edu; douglas.rothman@yale.edu NR 33 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-01150-8 PY 2005 BP 87 EP 102 DI 10.1002/0470011505.ch7 D2 10.1002/0470011508 PG 16 WC Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BYH36 UT WOS:000298788900008 ER PT J AU Lindberg, DAB AF Lindberg, DAB TI Research opportunities and challenges in 2005 SO METHODS OF INFORMATION IN MEDICINE LA English DT Article; Proceedings Paper CT 49th Annual Conference of the German-Society-for-Medical-Informatics-Biometry-and-Epidemiology CY SEP 26-30, 2004 CL Innsbruck, AUSTRIA SP German Soc Med Informat Biometry & Epidemiol DE literature review; medical informatics; computerized patient record; population surveillance; cohort studies ID US; STANDARD; JAPAN; NIH AB Objectives. Biomedical informatics practice and research have become so brood that I will comment on only three areas. These are the electronic health record; prospective population studies, and interactive publications. Methods. Review of the literature, Internet resources and material and reports generated by internal and external research projects. Results: Development of an electronic health record continues to be problematic in the U.S. A number of large-scale prospective cohort studies of normal populations are now actively occurring or in planning stages in a number of countries; these present special research opportunities in biomedical informatics. Although there are engineering challenges to the implementation of interactive publications, they have the potential to enhance understanding, learning, and memory of scientific and health concepts. Conclusions: Three areas of bio-medical informatics challenge us and offer interesting and worthy research opportunities. These include the electronic health record, prospective cohort studies, and interactive publications. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Lindberg, DAB (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM lindberg@nlm.nih.gov NR 20 TC 8 Z9 8 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2005 VL 44 IS 4 BP 483 EP 486 PG 4 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 972YQ UT WOS:000232490100002 PM 16342914 ER PT J AU Bozue, JA Parthasarathy, N Phillips, LR Cote, CK Fellows, PF Mendelson, I Shafferman, A Friedlander, AM AF Bozue, JA Parthasarathy, N Phillips, LR Cote, CK Fellows, PF Mendelson, I Shafferman, A Friedlander, AM TI Construction of a rhamnose mutation in Bacillus anthracis affects adherence to macrophages but not virulence in guinea pigs SO MICROBIAL PATHOGENESIS LA English DT Article DE Bacillus anthracis; anthrax; spores; exosporium; rhamnose; rml genes ID COLLAGEN-LIKE REGION; DTDP-RHAMNOSE; PROTECTIVE ANTIGEN; ALVEOLAR MACROPHAGES; GENOME SEQUENCE; CELL-WALLS; EXOSPORIUM; CEREUS; SPORES; IDENTIFICATION AB Carbohydrate analyses of whole-spore extracts have confirmed the presence of rhamnose in the spore of the fully virulent Ames strain of bacillus anthracis. A gene cluster containing loci with high homology to the rhamnose biosynthetic genes, rmlACBD, was identified within the B. anthracis chromosome. The first gene of this cluster, rmlA, was inactivated by forming a merodiploid cointegrate using an internal fragment of the gene within the Ames strain of B. anthracis to construct the mutant strain Ames-JAB1. Carbohydrate analysis of spores from this mutant demonstrated the loss of rhamnose. When assaying for spore infection of macrophages, we detected a significant decrease in the recovery with the Ames-JAB1 strain compared to the recovery with the Ames wild-type strain. When pre-treating macrophages with cytochalasin-D, spores of the mutant were further hindered in recovery, indicating that the spores were not able to bind as well to the macrophages. However, in guinea pigs challenge experiments, no difference in virulence was observed between the mutant and wild-type si rains. These results suggest that the incorporation of rhamnose into the spore coat of B. anthracis is required for optimal interaction with macrophages but is not required for full virulence in this animal model. (C) 2004 Published by Elsevier Ltd. C1 USA, Med Res Inst Infect Dis, Bacteriol Div, Ft Detrick, MD 21702 USA. NCI, Div Canc Treatment & Diagnosis, Dev Therapeut Program, Biol Testing Branch, Frederick, MD 21702 USA. Israel Inst Biol Res, IL-70450 Ness Ziona, Israel. USA, Med Res Inst Infect Dis, Frederick, MD USA. RP Bozue, JA (reprint author), USA, Med Res Inst Infect Dis, Bacteriol Div, 1425 Porter St, Ft Detrick, MD 21702 USA. EM joel.bozue@us.army.mil FU NCI NIH HHS [N01-CO-5600] NR 41 TC 37 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD JAN PY 2005 VL 38 IS 1 BP 1 EP 12 DI 10.1016/j.micpath.2004.10.001 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA 893BT UT WOS:000226695000001 PM 15652290 ER PT J AU Isenberg, JS Ridnour, LA Espey, MG Wink, DA Roberts, DD AF Isenberg, JS Ridnour, LA Espey, MG Wink, DA Roberts, DD TI Nitric oxide in wound-healing SO MICROSURGERY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; NF-KAPPA-B; DIABETIC FOOT ULCERS; L-ARGININE; GROWTH-FACTOR; COLLAGEN-SYNTHESIS; MYOCUTANEOUS FLAPS; ENDOTHELIAL-CELLS; DEPENDENT PATHWAY; DEFICIENT MICE AB Modulation of the complex process of wound-healing remains a surgical challenge. Little improvement beyond controlling infection, gentle tissue handling, and debridement of necrotic tissue has been had in the modern era. However, increasing appreciation of the process from a biomolecular perspective offers the potential for making significant strides in wound modulation. The bioactive molecule nitric oxide was found to have wide-ranging impact on cellular activities, including the cellular responses engendered by wound healing. Current research suggests that nitric oxide and several nitric oxide donors can exert biologic effects, although the particular net responses of cells contributing to wound repair are context-dependent. (c) 2005 Wiley-Liss, Inc. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Isenberg, JS (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM isenberj@mail.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 88 TC 48 Z9 55 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0738-1085 J9 MICROSURG JI Microsurgery PY 2005 VL 25 IS 5 BP 442 EP 451 DI 10.1002/micr.20166 PG 10 WC Surgery SC Surgery GA 952KS UT WOS:000231003000014 PM 16044466 ER PT J AU Isenberg, JS Tabatabai, N Spinelli, HM AF Isenberg, JS Tabatabai, N Spinelli, HM TI Nitric oxide modulation of low-density mononuclear cell transendothelial migration SO MICROSURGERY LA English DT Article ID VASCULAR ENDOTHELIAL-CELLS; THERAPEUTIC IMPLICATIONS; TUMOR ANGIOGENESIS; GROWTH-FACTOR; L-ARGININE; PERMEABILITY; CYTOKINE; EXPRESSION; JUNCTIONS; PROTEINS AB The blood-endothelial cell interface is a region of significant importance in many physiologic and pathologic processes. Blood-borne macromolecules and cells gain access to the subendothelial space and extravascular tissues by traversing the endothelium. Yet the various factors responsible for modulation of this process remain only partially elucidated. Several agents were found to be involved in this process, including nitric oxide (NO) and vascular endothelial growth factor (VEGF). It is known that under stress conditions (e.g., inflammation), NO can modulate the permeability of endothelial-cell monolayers to low-density mononuclear cells (LDMNCs). However, it is not known if NO can modulate such effects in the absence of inflammatory stimulation. In the present study, we utilized a Transwell chamber model to examine enclothelial-cell monolayer permeability to LDMNCs in the absence of inflammatory stimuli. We noted that NO donor and L-arginine increased transendothelial-cell migration, whereas nitric oxide synthase (NOS) inhibition decreased migration. These effects were not significantly abrogated by VEGF antibody, suggesting that they were not VEGF-dependent. (c) 2005 Wiley-Liss, Inc. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Coll Med, Dept Surg, New York, NY USA. RP Isenberg, JS (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A29,1500 Ctr Dr, Bethesda, MD 20892 USA. EM isenberj@mail.nih.gov NR 37 TC 2 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 0738-1085 J9 MICROSURG JI Microsurgery PY 2005 VL 25 IS 5 BP 452 EP 456 DI 10.1002/micr.20144 PG 5 WC Surgery SC Surgery GA 952KS UT WOS:000231003000015 PM 16032722 ER PT J AU Barrientos, LG Gronenborn, AM AF Barrientos, LG Gronenborn, AM TI The highly specific carbohydrate-binding protein cyanovirin-N: Structure, anti-HIV/Ebola activity and possibilities for therapy SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review DE cyanovirin-N; HIV; GP120; Ebola; GP(1,2); SARS; microbicidal agent; high-mannose oligosaccharides ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INACTIVATING PROTEIN; DOMAIN-SWAPPED DIMER; CIRCULAR-PERMUTED VARIANT; HIGH-MANNOSE OLIGOSACCHARIDES; EBOLA-VIRUS; SEXUAL TRANSMISSION; ENVELOPE GLYCOPROTEINS; RELATIVE ORIENTATION; ANTIVIRAL ACTIVITY AB Cyanovirin-N (CV-N), a cyanobacterial lectin, is a potent viral entry inhibitor currently under development as a microbicide against a broad spectrum of enveloped viruses. CV-N was originally identified as a highly active anti-HIV agent and later, as a virucidal agent against other unrelated enveloped viruses Such as Ebola, and possibly other viruses. CV-N's antiviral activity appears to involve unique recognition of N-linked high-mannose oligosaccharides, Man-8 and Man-9, on the viral surface glycoproteins. Due to its distinct mode of action and opportunities for harnessing the associated interaction for therapeutic intervention, a substantial body of research on CV-N has accumulated since its discovery in 1997. In this review we focus in particular on structural studies on CV-N and their relationship to biological activity. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Barrientos, LG (reprint author), Ctr Dis Control & Prevent, DVRD, NCID, Special Pathogens Branch, Mailstop G14, Atlanta, GA 30333 USA. EM lbarrientos1@cdc.gov; gronenborn@nih.gov NR 86 TC 65 Z9 70 U1 3 U2 17 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD JAN PY 2005 VL 5 IS 1 BP 21 EP 31 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 891RA UT WOS:000226597000003 PM 15638789 ER PT S AU Thimme, R Bukh, J Spangenberg, HC Wieland, SF Blum, HE Purcell, RH Chisari, FV AF Thimme, R. Bukh, J. Spangenberg, H. C. Wieland, S. F. Blum, H. E. Purcell, R. H. Chisari, F. V. BE VonWeizsacker, F Roggendorf, M TI T-Cell Response to Hepatitis B and C Virus: Lessons from the Chimpanzee Model SO MODELS OF VIRAL HEPATITIS SE Monographs in Virology LA English DT Article; Book Chapter ID ACUTE VIRAL-HEPATITIS; LYMPHOCYTE RESPONSE; IMMUNE-RESPONSE; PROTECTIVE IMMUNITY; INFECTION; CLEARANCE; PERSISTENCE; DETERMINANTS; REPLICATION; DISEASE C1 [Thimme, R.; Spangenberg, H. C.; Blum, H. E.] Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. [Bukh, J.; Purcell, R. H.] NIH, Hepatitis Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. [Thimme, R.; Wieland, S. F.; Chisari, F. V.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Thimme, R (reprint author), Univ Freiburg, Dept Med 2, Hugstetterstr 55, D-79106 Freiburg, Germany. EM thimme@med1.ukl.uni-freiburg.de NR 34 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0077-0965 BN 978-3-8055-7809-7 J9 MONOGR VIROL JI Monogr. Virol. PY 2005 VL 25 BP 66 EP 80 DI 10.1159/000084321 PG 15 WC Gastroenterology & Hepatology; Virology SC Gastroenterology & Hepatology; Virology GA BKL91 UT WOS:000268459300006 ER PT J AU Ning, EL Ronchetti, R Torres-Cabala, CA Teller, LS AF Ning, EL Ronchetti, R Torres-Cabala, CA Teller, LS TI Chromogenic in situ hybridization (CISH), a helpful tool for the pathologist to identify HER2/NEU amplification in breast carcinomas. Comparative study with IHC and FISH SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 173 BP 40A EP 40A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900174 ER PT J AU Atkins, KA Jeronimo, J Stoler, M AF Atkins, KA Jeronimo, J Stoler, M CA ALTS Trial TI Women with squamous cell carcinoma but mildly abnormal cytology: Review of the ALTS trial cases SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ Virginia, Charlottesville, VA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 265 BP 60A EP 60A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900266 ER PT J AU Fetsch, PA Abati, A AF Fetsch, PA Abati, A TI HER2 immunostaining in cytologic samples of metastatic breast cancer: Does antibody clone and pretreatment method effect results? SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 287 BP 65A EP 65A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900288 ER PT J AU Maygarden, SJ Funkhouser, W Flake, G Slebos, R Detterbeck, F Taylor, J Rivera, M AF Maygarden, SJ Funkhouser, W Flake, G Slebos, R Detterbeck, F Taylor, J Rivera, M TI Comparison of biopsy and cytology samples taken with the light induced fluorescence endoscopy (LIFE) bronchoscopy system SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ Sch Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 320 BP 72A EP 72A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900321 ER PT J AU Schinstine, M Filie, A Wilson, W Stetler-Stevenson, M Abati, A AF Schinstine, M Filie, A Wilson, W Stetler-Stevenson, M Abati, A TI Subsequent detection of lymphoid malignancy in cerebrospinal fluid (CSF) previously diagnosed as atypical or suspicious SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 340 BP 76A EP 76A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900341 ER PT J AU Aisner, DL Rosenberg, SA Berman, DM AF Aisner, DL Rosenberg, SA Berman, DM TI Loss of S100 immunoreactivity in metastatic melanoma SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 367 BP 82A EP 82A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900368 ER PT J AU Berman, DM Wincovitch, S Garfield, S Romeo, MJ AF Berman, DM Wincovitch, S Garfield, S Romeo, MJ TI Three-dimensional modeling of pigmented lesions can distinguish between benign and malignant melanocytes SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 369 BP 82A EP 82A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900370 ER PT J AU Hartmann, DP Kallakury, BVS Luka, J Appella, EA Owor, G Jones, DM Sheehan, CE Azumi, N Ross, JS AF Hartmann, DP Kallakury, BVS Luka, J Appella, EA Owor, G Jones, DM Sheehan, CE Azumi, N Ross, JS TI Immunohistochemical expression of the PPM1D/wip-1 protein correlates with aggressive tumor behavior in invasive colorectal carinomas (CRCS) SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Georgetown Univ Hosp, Washington, DC 20007 USA. Trevigen Inc, Gaithersburg, MD USA. Albany Med Coll, Albany, NY 12208 USA. NIH, GRS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 479 BP 105A EP 106A PG 2 WC Pathology SC Pathology GA 884WR UT WOS:000226117900480 ER PT J AU Berman, DM Wang, YW Liu, Z Dong, Q Burke, L Liotta, L Fisher, R Xu, X AF Berman, DM Wang, YW Liu, Z Dong, Q Burke, L Liotta, L Fisher, R Xu, X TI A functional polymorphism in an FIGS gene modulates the risk of bladder cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. MD Anderson Canc Ctr, Houston, TX USA. Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 591 BP 129A EP 129A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900592 ER PT J AU De Marzo, A Platz, EA Epstein, JI Billis, A Chan, TY Cheng, L Datta, M Ertoy-Baydar, D Farre, X Fine, S Iczkowski, KA Ittmann, M Knudsen, BS Loda, M Lopez-Beltran, A Magi-Galluzzi, C Mikuz, G Montironi, R Rabin, MA Sebo, T Sesterhenn, IA Shah, R Signoretti, S Simko, J Troncoso, P Tsuzuki, T van Leenders, GJLH Yang, X Zhou, M Figg, WD Hoque, A Lucia, MS AF De Marzo, A Platz, EA Epstein, JI Billis, A Chan, TY Cheng, L Datta, M Ertoy-Baydar, D Farre, X Fine, S Iczkowski, KA Ittmann, M Knudsen, BS Loda, M Lopez-Beltran, A Magi-Galluzzi, C Mikuz, G Montironi, R Rabin, MA Sebo, T Sesterhenn, IA Shah, R Signoretti, S Simko, J Troncoso, P Tsuzuki, T van Leenders, GJLH Yang, X Zhou, M Figg, WD Hoque, A Lucia, MS TI Interobserver reproducibility of a proposed classification of focal prostate atrophy lesions SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Johns Hopkins, Baltimore, MD USA. Univ Colorado, Boulder, CO 80309 USA. Univ Campinas, Campinas, SP, Brazil. Emory Univ, Atlanta, GA 30322 USA. VA Med Ctr, Gainesville, FL USA. Univ Cordoba, E-14071 Cordoba, Spain. Cleveland Clin, Cleveland, OH 44106 USA. Innsbruck Med Univ, Innsbruck, Austria. Polytech U Som, Ancona, Italy. Mayo Clin, Rochester, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Nagoya DRC Hosp, Nagoya, Aichi, Japan. Northwestern Univ, Evanston, IL 60208 USA. NIH, Bethesda, MD 20892 USA. Indiana Univ, Bloomington, IN 47405 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber, Boston, MA USA. RI Billis, Athanase/D-7365-2012; BAYDAR, DILEK/I-9610-2013; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 622 BP 135A EP 135A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900623 ER PT J AU Deas-Wooten, KD Herrmann, PC Torres-Cabala, CA Linehan, MW Merino, MJ AF Deas-Wooten, KD Herrmann, PC Torres-Cabala, CA Linehan, MW Merino, MJ TI Expression of oxidative complex enzymes assist in the differential diagnosis of renal tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 624 BP 136A EP 136A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900625 ER PT J AU Dhir, R Datta, MW Melamed, J Becich, MJ Bosland, MC Kajdacsy-Balla, AA Orenstein, J Silver, S Berman, J AF Dhir, R Datta, MW Melamed, J Becich, MJ Bosland, MC Kajdacsy-Balla, AA Orenstein, J Silver, S Berman, J TI Changes in tumor and HGPIN characteristics in radical prostatectomy specimens from 1990 to 2004: Results from the NCI cooperative prostate cancer tissue resource (CPCTR) SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. NYU, New York, NY USA. Univ Illinois, Chicago, IL USA. George Washington Univ, Washington, DC USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 626 BP 136A EP 136A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900627 ER PT J AU Torres-Cabala, CA Ning, EMLL Palau, MA Zbar, B Linehan, WM Merino, MK AF Torres-Cabala, CA Ning, EMLL Palau, MA Zbar, B Linehan, WM Merino, MK TI Expression of KIT in hereditary renal cell carcinoma SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 772 BP 167A EP 167A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117900773 ER PT J AU Khan, M Stoler, MH Schiffman, M AF Khan, M Stoler, MH Schiffman, M CA ALTS Grp TI The yield of endocervical curretage (ECC) in the work-up of cervical intraepithelial neoplasia SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 873 BP 188A EP 188A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901026 ER PT J AU Li Ning, EML Ricketts, RSJ Palau, MA Otis, C Roberts, DD Merino, MJ AF Li Ning, EML Ricketts, RSJ Palau, MA Otis, C Roberts, DD Merino, MJ TI In search of new molecular markers in the diagnosis of endometrial cancer SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Springfield, MA 01199 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 890 BP 191A EP 192A PG 2 WC Pathology SC Pathology GA 884WR UT WOS:000226117901043 ER PT J AU Elghetany, MT Bryant, B Alter, BP AF Elghetany, MT Bryant, B Alter, BP TI Bone marrow expression of p53, caspase-3, and WT-1 proteins in inherited and acquired cytopenias: A study of 106 patients SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Natl Canc Inst, Rockville, MD USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1063 BP 229A EP 229A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901216 ER PT J AU Fu, K Dave, S Wright, G Weisenburger, DD Greiner, TC Ott, G Muller-Hermelink, HK Rimsza, LM Braziel, RM Gascoyne, RD Delabie, J Campo, E Jaffe, ES Chiorazzi, M Zhao, H Chan, WC Staudt, LM AF Fu, K Dave, S Wright, G Weisenburger, DD Greiner, TC Ott, G Muller-Hermelink, HK Rimsza, LM Braziel, RM Gascoyne, RD Delabie, J Campo, E Jaffe, ES Chiorazzi, M Zhao, H Chan, WC Staudt, LM CA LLMPP TI Molecular diagnosis of Burkitt lymphoma using gene expression profiling SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ Nebraska, Med Ctr, NCI, Lincoln, NE 68583 USA. Univ Wurzburg, D-97070 Wurzburg, Germany. Univ Arizona, Tucson, AZ 85721 USA. Univ Oregon, Eugene, OR 97403 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, E-08007 Barcelona, Spain. NR 0 TC 2 Z9 2 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1067 BP 230A EP 230A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901220 ER PT J AU Greiner, T Hacia, J Rosenwald, A Weisenburger, D Smith, L Jaffe, E Gascoyne, R Campo, E Mueller-Hermelink, K Ott, G Delabie, J Braziel, R Standt, L Chan, W AF Greiner, T Hacia, J Rosenwald, A Weisenburger, D Smith, L Jaffe, E Gascoyne, R Campo, E Mueller-Hermelink, K Ott, G Delabie, J Braziel, R Standt, L Chan, W TI MRNA expression profile of p53 mutant or ATM mutant cases of mantle cell lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Univ So Calif, Los Angeles, CA USA. Univ Wurzburg, Wurzburg, Germany. NCI, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Barcelona, Barcelona, Spain. Norwegian Radium Hosp, Oslo, Norway. Univ Oregon, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1077 BP 232A EP 232A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901230 ER PT J AU Martinez, A Pittaluga, S Rudelius, M Fountaine, T Jaffe, ES Raffeld, M AF Martinez, A Pittaluga, S Rudelius, M Fountaine, T Jaffe, ES Raffeld, M TI Activation of the plasma cell associated transcription factor XBP-1 in B-cell NHL SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Natl Canc Inst, Bethesda, MD USA. Hosp del Mar, Barcelona, Spain. RI Martinez, Antonio/D-8188-2012 OI Martinez, Antonio/0000-0003-0790-9017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1117 BP 241A EP 241A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901270 ER PT J AU Ozer, O Lee, S Jayathilaka, N Shi, R Sun, M Ge, X Bouffard, G Wang, SM Rowley, JD AF Ozer, O Lee, S Jayathilaka, N Shi, R Sun, M Ge, X Bouffard, G Wang, SM Rowley, JD TI Unique gene expression profiles and novel transcripts in acute myeloid leukemia with recurrent translocations identified by SAGE (Serial analysis of gene expression) SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ Chicago, Chicago, IL 60637 USA. Northwestern Univ, Evanston, IL USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1134 BP 244A EP 245A PG 2 WC Pathology SC Pathology GA 884WR UT WOS:000226117901287 ER PT J AU Prakash, S Fountaine, T Raffeld, M Jaffe, ES Pittalaga, S AF Prakash, S Fountaine, T Raffeld, M Jaffe, ES Pittalaga, S TI IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1144 BP 247A EP 247A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901297 ER PT J AU Warren, MV Howat, WJ Haynes, B McCafferty, J Fredrickson, TN Morse, HC Bradley, A AF Warren, MV Howat, WJ Haynes, B McCafferty, J Fredrickson, TN Morse, HC Bradley, A TI Pathology of haemopoietic neoplasms arising in blm deficient mice: Use of tissue microarrays for high throughput immunohistochemical analysis SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Sanger Inst, Cambridge, England. Addenbrookes Hosp, Cambridge, England. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1185 BP 256A EP 256A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901338 ER PT J AU Berhane, D Mannon, RB Swanson, SJ Hale, DA Kirk, AD Kleiner, DE AF Berhane, D Mannon, RB Swanson, SJ Hale, DA Kirk, AD Kleiner, DE TI Quantitative assessment of glomerular infiltrates in chronic allograft glomerulopathy SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Howard Univ, Washington, DC 20059 USA. NIDDKD, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1227 BP 265A EP 265A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901380 ER PT J AU Calvo, KR Espina, V Rodriguez, A Hoatson, S Petricoin, EF Alexander, HR Liotta, LA Pingpank, JF AF Calvo, KR Espina, V Rodriguez, A Hoatson, S Petricoin, EF Alexander, HR Liotta, LA Pingpank, JF TI Clinical proteomics: In vivo molecular signaling profiles of human tumors, pre and post tumor perfusion with experimental chemotherapy SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, NIH, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1372 BP 297A EP 297A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901525 ER PT J AU Henson, DE Tilara, A Anderson, WA Schwartz, A AF Henson, DE Tilara, A Anderson, WA Schwartz, A TI Similar age-specific incidence rate patterns imply a biological relationship for ovarian cancers SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 George Washington Univ, Med Ctr, Washington, DC 20037 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1377 BP 298A EP 298A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901530 ER PT J AU Galli, S Tsokos, M AF Galli, S Tsokos, M TI Myogenin and MyoD expression in pediatric rhabdomyosarcoma (RMS) and other soft tissue tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1404 BP 303A EP 304A PG 2 WC Pathology SC Pathology GA 884WR UT WOS:000226117901557 ER PT J AU Funkhouser, WK Flake, GP Maygarden, SJ Detterbeck, FC Rivera, MP Slebos, RJC Taylor, JA AF Funkhouser, WK Flake, GP Maygarden, SJ Detterbeck, FC Rivera, MP Slebos, RJC Taylor, JA TI Detection of new primary in situ and invasive squamous lung carcinomas in patients with and without a history of lung or ENT squamous carcinomas SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1437 BP 310A EP 310A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901589 ER PT J AU Shilo, K Fukuoka, J Foss, RD Franks, TJ Travis, WD AF Shilo, K Fukuoka, J Foss, RD Franks, TJ Travis, WD TI Comparative immunohistochemical analysis of mucoepidermoid and adenoid cystic carcinomas of pulmonary and salivary gland origin SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1475 BP 318A EP 318A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901627 ER PT J AU Palau, MA Ronchetti, R Linehan, WM Ning, EML Torres-Cabala, C Merino, MJ AF Palau, MA Ronchetti, R Linehan, WM Ning, EML Torres-Cabala, C Merino, MJ TI Application of chromogenic in situ hybridization (CISH) in the differential diagnosis of renal tumors SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1545 BP 333A EP 333A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901697 ER PT J AU Sorbara, LR Dieffenbach, S Pham, T Pham, TH Raffeld, M AF Sorbara, LR Dieffenbach, S Pham, T Pham, TH Raffeld, M TI A simple one-tube method for DNA isolation and polymerase chain amplification of fresh and paraffin-embedded tissues SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Natl Inst Hlth, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1553 BP 335A EP 335A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901705 ER PT J AU Ahmed, A Torres-Cabala, C Linehan, M Merino, M Tsokos, M AF Ahmed, A Torres-Cabala, C Linehan, M Merino, M Tsokos, M TI Renal tumors in Hereditary Leiomyomatosis Renal Cell Carcinoma syndrome: Ultrastructural characterization SO MODERN PATHOLOGY LA English DT Meeting Abstract 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 C1 Natl Canc Inst, Bethesda, MD USA. Ctr Canc Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2005 VL 18 SU 1 MA 1566 BP 337A EP 337A PG 1 WC Pathology SC Pathology GA 884WR UT WOS:000226117901718 ER PT J AU Furumoto, H Ying, H Chandramouli, GVR Zhao, L Walker, RL Meltzer, PS Willingham, MC Cheng, SY AF Furumoto, H Ying, H Chandramouli, GVR Zhao, L Walker, RL Meltzer, PS Willingham, MC Cheng, SY TI An unliganded thyroid hormone p receptor activates the cyclin D1/cyclin-dependent kinase/retinoblastoma/E2F pathway and induces pituitary tumorigenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NEGATIVE REGULATION; GENE-EXPRESSION; CELL-LINE; CYCLIN D1; TUMOR; RESISTANCE; BETA; MUTATION; NUCLEAR; MICE AB Thyroid-stimulating hormone (TSH)-secreting tumors (TSH-omas) are pituitary tumors that constitutively secrete TSH. The molecular genetics underlying this abnormality are not known. We discovered that a knockin mouse harboring a mutated thyroid hormone receptor (TR) beta (PV; TRbeta(PV/PV) mouse) spontaneously developed TSH-omas. TRbeta(PV/PV) mice lost the negative feedback regulation with highly elevated TSH levels associated with increased thyroid hormone levels (3,3',5-triiodo-L-thyronine [T3]). Remarkably, we found that mice deficient in all TRs (TRalpha1(-/-) TRbeta(-/-)) had similarly increased T3 and TSH levels, but no discernible TSH-omas, indicating that the dysregulation of the pituitary-thyroid axis alone is not sufficient to induce TSH-omas. Comparison of gene expression profiles by cDNA microarrays identified overexpression of cyclin D1 mRNA in TRbeta(PV/PV) but not in TRalpha1(-/-) TRbeta(-/-) mice. Overexpression of cyclin D1 protein led to activation of the cyclin D1/cyclin-dependent kinase/retinoblastoma protein/E2F pathway only in TRbeta(PV/PV) mice. The liganded TRbeta repressed cyclin D1 expression via tethering to the cyclin D1 promoter through binding to the cyclic AMP response element-binding protein. That repression effect was lost in mutant PV, thereby resulting in constitutive activation of cyclin D1 in TRbeta(PV/PV) mice. The present study revealed a novel molecular mechanism by which an unliganded TRbeta mutant acts to contribute to pituitary tumorigenesis in vivo and provided mechanistic insights into the understanding of pathogenesis of TSH-omas in patients. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Human Genome Res Inst, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Rm 5128, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov NR 30 TC 70 Z9 72 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2005 VL 25 IS 1 BP 124 EP 135 DI 10.1128/MCB.25.1.124-135.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 886NZ UT WOS:000226236900011 PM 15601836 ER PT J AU Weber, A Liu, JH Collins, I Levens, D AF Weber, A Liu, JH Collins, I Levens, D TI TFIIH operates through an expanded proximal promoter to fine-tune c-myc expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR TFIIH; XERODERMA-PIGMENTOSUM; GENE-EXPRESSION; MESSENGER-RNA; DNA-REPAIR; ACTIVATION DOMAINS; IN-VITRO; PROTEIN; ESCAPE AB A continuous stream of activating and repressing signals is processed by the transcription complex paused at the promoter of the c-myc proto-oncogene. The general transcription factor IIH (TFIIH) is held at promoters prior to promoter escape and so is well situated to channel the input of activators and repressors to modulate c-myc expression. We have compared cells expressing only a mutated p89 (xeroderma pigmentosum complementation group B [XPB]), the largest TFIIH subunit, with the same cells functionally complemented with the wild-type protein (XPB/wt-p89). Here, we show structural, compositional, and functional differences in transcription complexes between XPB and XPB/wt-89 cells at the native c-myc promoter. Remarkably, although the mean levels of c-Myc are only modestly elevated in XPB compared to those in XPB/wt-p89 cells, the range of expression and the cell-to-cell variation of c-Myc are markedly increased. Our modeling indicates that the data can be explained if TFIIH integrates inputs from multiple signals, regulating transcription at multiple kinetically equivalent steps between initiation and promoter escape. This helps to suppress the intrinsic noise of transcription and to ensure the steady transcriptional output of c-myc necessary for cellular homeostasis. C1 NCI, Gene Regulat Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Mainz, Inst Pathol, D-6500 Mainz, Germany. RP Levens, D (reprint author), NCI, Gene Regulat Sect, Pathol Lab, Ctr Canc Res, Bldg 10,Rm 2N106, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 77 TC 46 Z9 47 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2005 VL 25 IS 1 BP 147 EP 161 DI 10.1128/mcb.25.1.147-161.2005 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 886NZ UT WOS:000226236900013 PM 15601838 ER PT J AU Rozenblatt-Rosen, O Hughes, CM Nannepaga, SJ Shanmugam, KS Copeland, TD Guszczynski, T Resau, JH Meyerson, M AF Rozenblatt-Rosen, O Hughes, CM Nannepaga, SJ Shanmugam, KS Copeland, TD Guszczynski, T Resau, JH Meyerson, M TI The parafibromin tumor suppressor protein is part of a human Paf1 complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; HISTONE METHYLTRANSFERASE COMPLEX; TRANSCRIPTION ELONGATION-FACTORS; SACCHAROMYCES-CEREVISIAE; HEREDITARY HYPERPARATHYROIDISM; GENE-EXPRESSION; BINDING-PROTEIN; IN-VIVO; METHYLATION; HRPT2 AB Parafibromin, the product of the HRPT2 (hyperparathyroidism-jaw tumor syndrome 2) tumor suppressor gene, is the human homologue of yeast Cdc73, part of the yeast RNA polymerase II/Paf1 complex known to be important for histone modification and connections to posttranscriptional events. By purifying cellular parafibromin and characterizing its associated proteins, we have identified a human counterpart to the yeast Paf1 complex including homologs of Leo1, Paf1, and Ctr9. Like the yeast complex, the parafibromin complex associates with the nonphosphorylated and Ser2 and Ser5 phosphorylated forms of the RNA polymerase II large subunit. Immunofluorescence experiments show that parafibromin is a nuclear protein. In addition, cotransfection data suggest that parafibromin can interact with a histone methyltransferase complex that methylates histone H3 on lysine 4. Some mutant forms of parafibromin lack association with hPaf1 complex members and with the histone methyltransferase complex, suggesting that disruption of these complexes may correlate with the oncogenic process. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Boston, MA USA. NCI, Canc Res Ctr, Lab Prot Dynam & Signaling, Frederick, MD USA. Van Andel Inst, Mol Microbiol Lab, Grand Rapids, MI USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 36 TC 152 Z9 159 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2005 VL 25 IS 2 BP 612 EP 620 DI 10.1128/MCB.25.2.612-620.2005 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 887EJ UT WOS:000226287800009 PM 15632063 ER PT J AU Huang, Y Intine, RV Mozlin, A Hasson, S Maraia, RJ AF Huang, Y Intine, RV Mozlin, A Hasson, S Maraia, RJ TI Mutations in the RNA polymerase III subunit Rpc11p that decrease RNA 3 ' cleavage activity increase 3 '-terminal oligo(U) length and La-dependent tRNA processing SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELONGATION-FACTOR TFIIS; METHIONYL-TRANSFER-RNA; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; TRANSCRIPTION TERMINATION; MESSENGER-RNA; PROTEIN; MATURATION; NUCLEAR AB Termination by RNA polymerase III (Pol III) produces RNAs whose 3' oligo(U) termini are bound by La protein, a chaperone that protects RNAs from 3' exonucleases and promotes their maturation. Multiple reports indicate that yeasts use La-dependent and -independent pathways for tRNA maturation, with defective pre-tRNAs being most sensitive to decay and most dependent on La for maturation and function. The Rpc11p subunit of Pol III shows homology with the zinc ribbon of TFIIS and is known to mediate RNA 3' cleavage and to be important for termination. We used a La-dependent opal suppressor, tRNA(Ser)UGAM, which suppresses ade6-704 and the accumulation of red pigment, to screen Schizzosaccaromyces pombe for rpc11 mutants that increase tRNA-mediated suppression. Analyses of two zinc ribbon mutants indicate that they are deficient in Pol III RNA 3' cleavage activity and produce pre-tRNA(Ser)UGAM transcripts with elongated 3'-oligo(U) tracts that are better substrates for La. A substantial fraction of pre-tRNA(Ser)UGAM contains too few 3' Us for efficient La binding and appears to decay in wild-type cells but has elongated oligo(U) tracts and matures along the La-dependent pathway in the mutants. The data indicate that Rpc11p limits RNA 3'-U length and that this significantly restricts pre-tRNAs to a La-independent pathway of maturation in fission yeast. C1 NICHHD, Lab Mol Growth Regulat, Bethesda, MD USA. RP Maraia, RJ (reprint author), 31 Ctr Dr,Room 2A25, Rockville, MD 20852 USA. EM maraiar@mail.nih.gov NR 39 TC 36 Z9 38 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2005 VL 25 IS 2 BP 621 EP 636 DI 10.1128/MCB.25.2.621-636.2005 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 887EJ UT WOS:000226287800010 PM 15632064 ER PT J AU Daelemans, D Costes, SV Lockett, S Pavlakis, GN AF Daelemans, D Costes, SV Lockett, S Pavlakis, GN TI Kinetic and molecular analysis of nuclear export factor CRM1 association with its cargo in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESONANCE ENERGY-TRANSFER; VIRAL MESSENGER-RNA; LIVING CELLS; PORE COMPLEX; NUCLEOCYTOPLASMIC TRANSPORT; INTRACELLULAR TRAFFICKING; PROTEIN DYNAMICS; SIGNAL; REV AB The nucleocytoplasmic transport receptor CRM1 mediates the export of macromolecules from the nucleus to the cytoplasm by forming a ternary complex with a cargo molecule and RanGTP. The in vivo mechanism of CRM1 export complex formation and its mobility throughout the nucleus have not been fully elucidated. More information is required to fully understand complex formation and the dynamics of CRM1-cargo-RanGTP complexes in space and time. We demonstrate true molecular interaction of CRM1 with its Rev cargo in living cells by using fluorescence resonance energy transfer (FRET). Interestingly, we found that the inhibitory effect of leptomycin B on this CRM1-cargo interaction is Ran dependent. Using fluorescence recovery after photobleaching (FRAP), we show that CRM1 moves at rates similar to that of free green fluorescent protein in the nucleoplasm. A slower mobility was detected on the nuclear membrane, consistent with known CRM1 interactions with nuclear pores. Based on these data, we propose an in vivo model in which CRM1 roams through the nucleus in search of high-affinity binding sites. CRM1 is able to bind Rev cargo in the nucleolus, and upon RanGTP binding a functional export complex is produced that is exported to the cytoplasm. C1 NCI, Human Retrovirus Sect, Frederick, MD 21701 USA. SAIC, Image Anal Lab, Frederick, MD 21701 USA. RP Daelemans, D (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium. EM dirk.daelemans@uz.kuleuven.ac.be; pavlakis@mail.nciferf.gov RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 61 TC 44 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2005 VL 25 IS 2 BP 728 EP 739 DI 10.1128/MCB.25.2.728-739.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 887EJ UT WOS:000226287800019 PM 15632073 ER PT J AU Levine, CG Mitra, D Sharma, A Smith, CL Hegde, RS AF Levine, CG Mitra, D Sharma, A Smith, CL Hegde, RS TI The efficiency of protein compartmentalization into the secretory pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; SIGNAL RECOGNITION PARTICLE; NEWLY SYNTHESIZED PROTEINS; CYTOSOLIC PRION PROTEIN; VIRUS PRECORE PROTEIN; IN-VIVO; ALZHEIMERS-DISEASE; TRANSLOCATION CHANNEL; ELONGATION ARREST; TRANSGENIC MICE AB Numerous proteins targeted for the secretory pathway are increasingly implicated in functional or pathological roles at alternative cellular destinations. The parameters that allow secretory or membrane proteins to reside in intracellular locales outside the secretory pathway remain largely unexplored. In this study, we have used an extremely sensitive and quantitative assay to measure the in vivo efficiency of signal sequence-mediated protein segregation into the secretory pathway. Our findings reveal that segregation efficiency varies tremendously among signals, ranging from >95 to <60%. The nonsegregated fraction is generated by a combination of mechanisms that includes inefficient signal-mediated translocation into the endoplasmic reticulum and leaky ribosomal scanning. The segregation efficiency of some, but not other signal sequences, could be influenced in cis by residues in the mature domain or in trans by yet unidentified cellular factors. These findings imply that protein compartmentalization can be modulated in a substrate-specific manner to generate biologically significant quantities of cytosolically available secretory and membrane proteins. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NINDS, Light Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov NR 70 TC 75 Z9 78 U1 2 U2 10 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2005 VL 16 IS 1 BP 279 EP 291 DI 10.1091/mbc.E04-06-0508 PG 13 WC Cell Biology SC Cell Biology GA 882QW UT WOS:000225954400029 PM 15496459 ER PT J AU Braun, DC Cao, YY Wang, SM Garfield, SH Hur, GM Blumberg, PM AF Braun, DC Cao, YY Wang, SM Garfield, SH Hur, GM Blumberg, PM TI Role of phorbol ester localization in determining protein kinase C or RasGRP3 translocation: Real-time analysis using fluorescent ligands and proteins SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID 12,13-DIBUTYRATE BINDING; RECEPTOR-BINDING; TUMOR PROMOTERS; BREAST-CANCER; ALPHA; DOMAINS; DELTA; DIACYLGLYCEROL; ACTIVATION; INHIBITOR AB The diacylglycerol signaling pathway, involving protein kinase C (PKC) and RasGRP, is a promising therapeutic target for both cancer and other indications. The phorbol esters, ultrapotent diacylglycerol analogues, bind to and activate PKC and RasGRP. Here, using fluorescent phorbol esters and complementary fluorescent PKC and RasGRP constructs, we determined the localization of the phorbol ester as a function of time after addition and how the resultant PKC or RasGRP3 translocation related to ligand localization. For these studies, we prepared fluorescently labeled phorbol esters of varying lipophilicities based on the BODIPY FL (green) or BODIPY 581/591 (red) fluorophores, and by using fusion constructs of green fluorescent protein or DsRed with PKC isoforms or RasGRP3 expressed in Chinese hamster ovary cells, we simultaneously compared the kinetics and pattern of localization of PKC or RasGRP3 with that of the fluorescent red or green phorbol esters. Binding assays showed that the fluorescent derivatives were potent ligands. Uptake followed a one-compartment pharmacokinetic model with a half-time of minutes to hours, depending on the ligand, and all of the fluorescent phorbol esters localized primarily to intracellular membranes, with little plasma membrane localization. The fluorescent phorbol esters induced translocation of and generally colocalized with PKCdelta or RasGRP3. However, PKCalpha and, initially, PKCdelta, translocated to the plasma membrane, in which little phorbol ester accumulated. The findings argue that the rate of uptake of phorbol esters influences the subsequent pattern of PKCdelta translocation, and that the specificity for PKCalpha. translocation is dominated by factors other than the localization of the ligand. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Gallaudet Univ, Dept Biol, Washington, DC USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Blumberg, PM (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37,Room 4048,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov NR 44 TC 21 Z9 21 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2005 VL 4 IS 1 BP 141 EP 150 PG 10 WC Oncology SC Oncology GA 888DX UT WOS:000226355500014 PM 15657361 ER PT J AU Rundhaug, JE Hawkins, KA Pavone, A Gaddis, S Kil, H Klein, RD Berton, TR McCauley, E Johnson, DG Lubet, RA Fischer, SM Aldaz, CM AF Rundhaug, JE Hawkins, KA Pavone, A Gaddis, S Kil, H Klein, RD Berton, TR McCauley, E Johnson, DG Lubet, RA Fischer, SM Aldaz, CM TI SAGE profiling of UV-Induced mouse skin squamous cell carcinomas, comparison with acute UV irradiation effects SO MOLECULAR CARCINOGENESIS LA English DT Article DE SAGE; gene expression; skin; UV light; squamous cell carcinomas ID HUMAN EPIDERMAL-KERATINOCYTES; GENE-EXPRESSION; ULTRAVIOLET-B; SERIAL ANALYSIS; REGULATED GENES; MICE LACKING; CANCER; CARCINOGENESIS; DIFFERENTIATION; IDENTIFICATION AB Ultraviolet (UV) irradiation is the primary environmental insult responsible for the development of most common skin cancers. To better understand the multiple molecular events that contribute to the development of UV-induced skin cancer, in a first study, serial analysis of gene expression (SAGE) was used to compare the global gene expression profiles of normal SKH-1 mice epidermis with that of UV-induced squamous cell carcinomas (SCCs) from SKH-1 mice. More than 200 genes were found to be differentially expressed in SCCs compared to normal skin (P < 0.0005 level of significance). As expected, genes related to epidermal proliferation and differentiation were deregulated in SCCs relative to normal skin. However, various novel genes, not previously associated with skin carcinogenesis, were also identified as deregulated in SCCs. Northern blot analyses on various selected genes validated the SAGE findings: caspase-14 (reduced 8.5-fold in SCCs); cathepsins D and S (reduced 3-fold and increased 11.3-fold, respectively, in SCCs); decorin, glutathione S-transferase omega-1, hypoxia-inducible factor 1alpha, insulin-like growth factor binding protein-7, and matrix metalloproteinase-13 (increased 18-, 12-, 12-, 18.3-, and 11-folds, respectively, in SCCs). Chemokine (C-C motif), ligand 27 (CCL27), which was found downregulated 12.7-fold in SCCs by SAGE, was also observed to be strongly downregulated 6-24 h after a single and multiple UV treatments. In a second independent study we compared the expression profile of UV-irradiated versus sham-treated SKH-1 epidermis. Interestingly, numerous genes determined to be deregulated 8 h after a single UV dose were also deregulated in SCCs. For instance, genes whose expression was upregulated both after acute UV-treated skin and SCCs included keratins 6 and 16, small proline-rich proteins, and S100 calcium binding protein A9. Studies like those described here do not only provide insights into genes and pathways involved in skin carcinogenesis but also allow us to identify early UV irradiation deregulated surrogate biomarkers of potential use in chemoprevention studies. (C) 2004 Wiley-Liss, Inc. C1 Univ Texas, MD Anderson Canc Ctr, Div Res, Dept Carcinogenesis, Smithville, TX 78957 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Fischer, SM (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Res, Dept Carcinogenesis, Sci Pk,POB 389, Smithville, TX 78957 USA. FU NCI NIH HHS [CA16672, CN05110]; NIEHS NIH HHS [ES07784, ES11047] NR 58 TC 33 Z9 34 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2005 VL 42 IS 1 BP 40 EP 52 DI 10.1002/mc.20064 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 882EQ UT WOS:000225922200005 PM 15547921 ER PT J AU Charmandari, E Chrousos, GP Ichijo, T Bhattacharyya, N Vottero, A Souvatzoglou, E Kino, T AF Charmandari, E Chrousos, GP Ichijo, T Bhattacharyya, N Vottero, A Souvatzoglou, E Kino, T TI The human glucocorticoid receptor (hGR) beta isoform suppresses the transcriptional activity of hGR alpha by interfering with formation of active coactivator complexes SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LIGAND-BINDING DOMAIN; NUCLEAR RECEPTOR; ESTROGEN-RECEPTOR; BETA-ISOFORM; DNA-BINDING; RESPONSE ELEMENTS; EXPRESSION; MULTIPLE; HORMONE; ACTIVATION AB The human glucocorticoid receptor (hGR) beta, a splicing variant of the classic receptor hGRalpha, functions as a dominant-negative inhibitor of hGRalpha. We explored the mechanism(s) underlying this effect of hGRbeta by evaluating the interactions of this isoform with known steroid receptor coactivators. We found that hGRbeta suppressed the transcriptional activity of both activation function (AF)-1 and AF-2 of hGRalpha, indicating that hGRbeta may exert its dominant-negative effect by affecting the function of coactivators that are attracted to these transactivation domains. hGRbeta bound to one of the p160 coactivators, the glucocorticoid receptor-interacting protein 1 (GRIP1) via its preserved AF-1 but not via its defective AF-2 in vitro. In a chromatin immunoprecipitation assay, hGRbeta prevented coprecipitation of GRIP1 with hGRalpha tethered to glucocorticoid response elements of the endogenous tyrosine aminotransferase promoter, whereas deletion of the AF-1 of hGRbeta abolished this effect. In further experiments, overexpression of GRIP1 attenuated the suppressive effect of hGRbeta on hGRalpha-mediated transactivation of the mouse mammary tumor virus promoter. Competition for binding to glucocorticoid response elements or heterodimerization with hGRalpha via the D loop dimerization interface occurred, but they were not necessary for the suppressive effect of hGRbeta on the transcriptional activity of hGRalpha. Our findings suggest that hGRbeta suppresses the transcriptional activity of hGRalpha by competing with hGRalpha for binding to GRIP1, and possibly other p160 coactivators, through its preserved AF-1. These findings suggest that participation of hGRbeta in the formation of a coactivator complex renders this complex ineffective. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 62 TC 66 Z9 73 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 2005 VL 19 IS 1 BP 52 EP 64 DI 10.1210/me.2004-0112 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 882NV UT WOS:000225946500005 PM 15459252 ER PT J AU Gunay-Aygun, M AF Gunay-Aygun, M TI 3-methylglutaconic aciduria: A common biochemical marker in various syndromes with diverse clinical features SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID NEUTROPENIA C1 NHGRI, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD 20892 USA. NIH, Off Director, Off Rare Dis, Intramural Program, Bethesda, MD 20892 USA. RP Gunay-Aygun, M (reprint author), NHGRI, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov NR 9 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2005 VL 84 IS 1 BP 1 EP 3 DI 10.1016/j.ymgme.2004.12.003 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 899VL UT WOS:000227173700001 PM 15719488 ER PT J AU Wu, YP Mizukami, H Matsuda, J Saito, Y Proia, RL Suzuki, K AF Wu, YP Mizukami, H Matsuda, J Saito, Y Proia, RL Suzuki, K TI Apoptosis accompanied by up-regulation of TNF-alpha death pathway genes in the brain of Niemann-Pick type C disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Niemann-Pick disease type C; neuronal death; TNF receptor; astrocyte ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; SANDHOFF-DISEASE; CELL-DEATH; ACTIVATION; NEURODEGENERATION; IDENTIFICATION; DEGENERATION; EXPRESSION AB Nieniann-Pick disease type C (NP-C) is an autosomal recessive neurovisceral storage disease with neurodegeneration caused by mutations in either the NPC-1 or NPC-2 gene. The murine ortholog of NPC-1 is mutated in BALB/c npc(nih) and this mutant mouse shows equally conspicuous neurodegeneration and loss of neurons. However, the molecular mechanisms causing neurodegeneration in NP-C remain elusive. Here, we report the presence of apoptotic cells detected by both TUNEL staining and electron microscopy in the cerebrum and cerebellurn of human patients and the mouse model. Moreover, we found that with progression of the disease process leading to neuronal cell death, an up-regulation of genes involved in the TNF-alpha death pathway caspase-8, FADD, TNFRp55, TRADD, and RIP-by an RNA protection assay. Furthermore, RT-PCR showed that TNF-alpha, mRNA expression level also increased Lip to 30-50-fold in the cerebellum of 7- and 9-week-old NP-C mice compared with wild-type mice. Elevated expression of TNF-alpha was detected in both neurons and astrocytes with TNF-alpha-expressing astrocytes distributed in the affected brain regions. Collectively, our results suggest that the cell death in the brain of NP-C disease occurs through apoptosis and it is mediated by the TNF receptor superfamily pathway. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lab Med, Chapel Hill, NC 27599 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. RP Wu, YP (reprint author), Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. EM Yun-PingW@intra.niddk.nih.gov RI Proia, Richard/A-7908-2012 FU NINDS NIH HHS [NS 24453] NR 33 TC 66 Z9 68 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2005 VL 84 IS 1 BP 9 EP 17 DI 10.1016/ymgme.2004.08.017 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 899VL UT WOS:000227173700003 PM 15639190 ER PT J AU Potteaux, S Combadiere, C Esposito, B Casanova, S Merval, R Ardouin, P Gao, JL Murphy, PM Tedgui, A Ziad, M AF Potteaux, S Combadiere, C Esposito, B Casanova, S Merval, R Ardouin, P Gao, JL Murphy, PM Tedgui, A Ziad, M TI Chemokine receptor CCRI disruption in bone marrow cells enhances atherosclerotic lesion development and inflammation in mice SO MOLECULAR MEDICINE LA English DT Article ID DEFICIENT MICE; KNOCKOUT MICE; PATHOGENESIS; ATHEROGENESIS; FRACTALKINE; REVEALS; DISEASE; ARTERY AB Several chemokines or chemokine receptors are involved in atherogenesis. CCR1 is expressed by macrophages and lymphocytes, two major cell types involved in the progression of atherosclerosis, and binds to lesion-expressed ligands. We examined the direct role of the blood-borne chemokine receptor CCR1 in atherosclerosis by transplanting bone marrow cells from either CCR1(+/+) or CCR1(-/-) mice into low-density lipoprotein-receptor (LDLr)-deficient mice. After exposure to an atherogenic diet for 8 weeks, no differences in fatty streak size or composition were detected between the 2 groups. After 12 weeks of atherogenic diet, however, an unexpected 70% increase in atherosclerotic lesion size in the thoracic aorta was detected in the CCR1(-/-) mice, accompanied by a 37% increase in the aortic sinus lesion area. CCR1(-/-) mice showed enhanced basal and concanavalin A-stimulated IFN-gamma production by spleen T cells and enhanced plaque inflammation. In conclusion, blood-borne CCR1 alters the immuno-inflammatory response in atherosclerosis and prevents excessive plaque growth and inflammation. C1 Hop Lariboisiere, INSERM, U689, F-75010 Paris, France. Hop Lariboisiere, INSERM, U543, Lab Immunol Cellulaire & Tissulaire, F-75010 Paris, France. Inst Gustave Roussy, Villejuif, France. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Ziad, M (reprint author), Hop Lariboisiere, INSERM, U689, 41 Bd Chapelle, F-75010 Paris, France. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 18 TC 36 Z9 40 U1 2 U2 3 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN-DEC PY 2005 VL 11 IS 1-12 BP 16 EP 20 DI 10.2119/2005-00028.Potteaux PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 041BS UT WOS:000237428600002 PM 16491201 ER PT J AU Fekete, RA Chattoraj, DK AF Fekete, RA Chattoraj, DK TI A cis-acting sequence involved in chromosome segregation in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID DNA-REPLICATION; PLASMID SEGREGATION; TERMINAL DOMAIN; BACTERIAL-DNA; ORIC REGION; LOCALIZATION; INITIATION; SITE; CONDENSATION; ORGANIZATION AB Eukaryotic chromosomes contain a locus, the centromere, at which force is applied to separate replicated chromosomes. A centromere analogue is also found in some bacterial plasmids and chromosomes, although not yet identified in the well-studied Escherichia coli chromosome. We aimed to identify centromere-like sequences in E. coli with the premise that such sequences would be the first to migrate towards the cell poles, away from the cell centre where DNA replication is believed to occur. We have labelled different loci on the chromosome by integrating arrays of binding sites for LacI-EYFP and phage lambdacI-ECFP and supplying these fusion proteins in trans. Comparison of such pairs of loci suggests the presence of a centromere-like site close to the origin of replication. Polar migration of the site was dependent on migS, a locus recently implicated in chromosome migration, thus providing strong support for migS being the E. coli centromere. C1 NCI, Biochem Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, CCR, NIH, Bldg 37, Bethesda, MD 20892 USA. EM chattord@mail.nih.gov NR 32 TC 55 Z9 55 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2005 VL 55 IS 1 BP 175 EP 183 DI 10.1111/j.1365-2958.2004.04392.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 882OX UT WOS:000225949300016 PM 15612926 ER PT J AU Mittal, S Song, XQ Vig, BS Landowski, CP Kim, I Hilfinger, JM Amidon, GL AF Mittal, Sachin Song, Xueqin Vig, Balvinder S. Landowski, Christopher P. Kim, Insook Hilfinger, John M. Amidon, Gordon L. TI Prolidase, a potential enzyme target for melanoma: Design of proline-containing dipeptide-like prodrugs SO MOLECULAR PHARMACEUTICS LA English DT Article DE bioinformatics; prolidase; enzyme targeting; melanoma; prodrugs; melphalan AB Bioinformatics tools such as Perl, Visual Basic, Cluster, and TreeView were used to analyze public gene expression databases in order to identify potential enzyme targets for prodrug strategies. The analyses indicated that prolidase might be a desirable enzyme target based on its differential expression in melanoma cancer cell lines and its high substrate specificity for dipeptides containing proline at the carboxy terminus. RT-PCR expression of prolidase and hydrolytic activity against N-glycyl-L-proline (GLY-PRO), a standard substrate of prolidase, determined in tumor cell lines, exhibited a high correlation (r(2) = 0.95). These results suggest the possibility of targeting prolidase with prodrugs of anticancer agents for enhanced selectivity. The feasibility of such a scenario was tested by (a) synthesizing prodrugs of melphalan that comprised linkage of the carboxy terminus of the L-phenylalanine moiety of melphalan to the N-terminus of L and D stereoisomers; of proline and (b) determining their bioconversion and antiproliferative activities in SK-MEL-5 cells, a melanoma cancer cell line with high expression levels of prolidase. The results of hydrolysis studies of the L- and D-proline prodrugs of melphalan, designated as prophalan-L and prophalan-D, respectively, indicated a similar to 7-fold higher rate of activation of prophalan-L compared to prophalan-D in SK-MEL-5 cell homogenates. Prophalan-L exhibited cytotoxicity (GI(50) = 74.8 mu M) comparable to that of melphalan (GI(50) = 57.0 mu M) in SK-MEL-5 cells while prophalan-D was ineffective, suggesting that prolidase-specific activation to the parent drug may be essential for cytotoxic action. Thus, melphalan prodrugs such as prophalan-L that are cleavable by prolidase offer the potential for enhanced selectivity by facilitating cytotoxic activity only in cells overexpressing prolidase. C1 [Mittal, Sachin; Song, Xueqin; Landowski, Christopher P.; Amidon, Gordon L.] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA. [Vig, Balvinder S.] Bristol Myers Squibb Co, Pharmaceut Res Inst, Exploratory Biopharmaceut & Stabil, New Brunswick, NJ 08903 USA. [Kim, Insook] NCI, Met Lab, NIH, Bethesda, MD 20892 USA. [Hilfinger, John M.] TSRL Inc, Ann Arbor, MI 48108 USA. RP Amidon, GL (reprint author), Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, 428 Church St, Ann Arbor, MI 48109 USA. EM glamidon@umich.edu OI Landowski, Christopher/0000-0003-1775-8646 FU NIH [R01-GM37188]; College of Pharmacy; University of Michigan FX This work was supported by NIH Grant R01-GM37188 and by the College of Pharmacy, University of Michigan. We thank Dr. Gustavo Rosania for providing the SK-MEL-5, U-251, NCI-H522, MCF-7, and K-562 cell lines. We also thank Dr. Kyung-Dall Lee for use of the 96-well plate reader in colorimetric assays. NR 35 TC 23 Z9 23 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JAN-FEB PY 2005 VL 2 IS 1 BP 37 EP 46 DI 10.1021/mp049922p PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JA UT WOS:000203538600006 PM 15804176 ER PT J AU Shah, BH Olivares-Reyes, JA Catt, KJ AF Shah, BH Olivares-Reyes, JA Catt, KJ TI The protein kinase C inhibitor Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a) pyrrolo(3,4-c)-carbazole] potentiates agonist-induced mitogen-activated protein kinase activation through tyrosine phosphorylation of the epidermal growth factor receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; N-TERMINAL KINASE; ANGIOTENSIN-II; MAP KINASE; COUPLED RECEPTORS; CANCER-CELLS; GO 6976; TRANSACTIVATION; PHOSPHATASES; PKC AB Protein kinase C (PKC) isoforms are important transducers of signals from G protein-coupled receptors (GPCRs) to diverse cellular targets, including extracellular signal-regulated kinases 1 and 2 (ERK1/2). Clone 9 rat hepatocytes (C9 cells) express receptors for angiotensin II (Ang II) type 1, lysophosphatidic acid (LPA), and epidermal growth factor (EGF), and their stimulation causes transient ERK1/2 phosphorylation through transactivation of the epidermal growth factor receptor ( EGFR). Inhibition of PKC by Go6983 [2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide], or PKC depletion by prolonged phorbol 12-myristate 13-acetate (PMA) treatment, attenuated ERK1/2 activation by Ang II and PMA, but not by LPA and EGF. In contrast, another PKC inhibitor, Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole], enhanced basal and agonist-stimulated phosphorylation of ERK1/2, which was not caused by alteration in receptor binding and internalization, stimulation of inositol phosphate production, or activation of Pyk2 and Src tyrosine kinases. However, Go6976 enhanced agonist-induced tyrosine phosphorylation of the EGF receptor, possibly through inhibition of protein tyrosine phosphatase (PTP), because the PTP inhibitor sodium orthovanadate mimicked the effects of Go6976. Selective blockade of EGF-R kinase by AG1478 [4-(3-chloroanilino)6,7-dimethoxyquinazoline] abolished the ERK1/2 activation induced by Go6976. Similar experiments were conducted in human embryonic kidney 293 cells, which express receptors for LPA and EGF but exhibit no significant cross-communication between them. Although Go6976 caused a significant increase in EGF-induced tyrosine phosphorylation of the EGF-R and subsequent ERK1/2 activation, it had no such effects on LPA-induced responses. In Chinese hamster ovary cells, which express receptors for LPA but not for EGF, Go6976 also had no significant effect on LPA-induced ERK1/2 activation. These data indicate that Go6976 potentiates agonist-induced ERK1/2 activation through stimulation of tyrosine phosphorylation of the EGF-R. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov NR 37 TC 16 Z9 16 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2005 VL 67 IS 1 BP 184 EP 194 DI 10.1124/mol.104.003533 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881KA UT WOS:000225865200021 PM 15465928 ER PT J AU Barbier, O Girard, H Inoue, Y Duez, H Villeneuve, L Kamiya, A Fruchart, JC Guillemette, C Gonzalez, FJ Staels, B AF Barbier, O Girard, H Inoue, Y Duez, H Villeneuve, L Kamiya, A Fruchart, JC Guillemette, C Gonzalez, FJ Staels, B TI Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor 4 alpha SO MOLECULAR PHARMACOLOGY LA English DT Article ID UDP-GLUCURONOSYLTRANSFERASE 1A8; HUMAN LIVER-MICROSOMES; FACTOR 4-ALPHA; TRANSCRIPTION FACTORS; RESPONSE ELEMENT; PROMOTER REGION; HUMAN COLON; X-RECEPTOR; METABOLISM; IDENTIFICATION AB UDP-glucuronosyltransferase (UGT) enzymes catalyze the glucuronidation reaction, which is a major pathway in the catabolism and elimination of numerous endo- and xenobiotics. Among the UGT enzyme family members, the UGT1A7, UGT1A8, UGT1A9, and UGT1A10 isoforms are issued from a single gene through differential splicing. However, these enzymes display distinct tissue-specific expression patterns. Indeed, UGT1A7, UGT1A8, and UGT1A10 are exclusively expressed in extrahepatic tissues, whereas UGT1A9 transcripts are found at high concentrations in liver. In the present study, we report that the liver-enriched hepatocyte nuclear factor 4 (HNF4)-alpha controls the hepatic expression of the UGT1A9 enzyme. Liver-specific disruption of the HNF4alpha gene in mice drastically decreases liver UGT1A9 mRNA levels. Furthermore, an HNF4alpha response element (HNF4alpha RE) was identified in the promoter of human UGT1A9 at position -372 to -360 base pairs by transient transfection, electrophoretic mobility shift assays, and chromatin immunoprecipitation experiments. It is interesting that this response element is absent in the proximal UGT1A7, UGT1A8, and UGT1A10 gene promoters. In conclusion, the present study identifies HNF4alpha as a major factor for the control of UGT1A9 hepatic expression and suggests that the absence of UGT1A7, UGT1A8, and UGT1A10 expression in the liver is caused by, at least in part, a few base pair changes in their promoter sequences in the region corresponding to the HNF4alpha RE of the UGT1A9 gene. C1 Inst Pasteur, INSERM, U545, Dept Atherosclerose,UR 545, F-59019 Lille, France. Univ Lille 2, Fac Pharm, Lille, France. CHUL, Res Ctr, Canada Res Chair Pharmacogen, Oncol & Mol Endocrinol Res Ctr, Laval, PQ, Canada. Univ Laval, Fac Pharm, Quebec City, PQ G1K 7P4, Canada. NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staels, B (reprint author), Inst Pasteur, INSERM, U545, Dept Atherosclerose,UR 545, 1 Rue Pr Calmette,BP 245, F-59019 Lille, France. EM bart.staels@pasteur-lille.fr RI Guillemette, Chantal/J-6463-2012; OI Staels, Bart/0000-0002-3784-1503 NR 41 TC 43 Z9 44 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2005 VL 67 IS 1 BP 241 EP 249 DI 10.1124/mol.104.003863 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 881KA UT WOS:000225865200027 PM 15470081 ER PT J AU Harrison, PJ Weinberger, DR AF Harrison, PJ Weinberger, DR TI Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence SO MOLECULAR PSYCHIATRY LA English DT Review DE dopamine; genetics; glutamate; NMDA receptor; psychosis; synaptic plasticity ID CATECHOL-O-METHYLTRANSFERASE; DORSOLATERAL PREFRONTAL CORTEX; METABOTROPIC GLUTAMATE RECEPTORS; BIPOLAR-AFFECTIVE-DISORDER; MESSENGER-RNA EXPRESSION; FAMILY-BASED ASSOCIATION; AMINO-ACID OXIDASE; RESONANCE-IMAGING MORPHOMETRY; MEDIODORSAL THALAMIC NUCLEUS; NEURONAL NICOTINIC RECEPTORS AB This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence. The morphological correlates of schizophrenia are subtle, and range from a slight reduction in brain size to localized alterations in the morphology and molecular composition of specific neuronal, synaptic, and glial populations in the hippocampus, dorsolateral prefrontal cortex, and dorsal thalamus. These findings have fostered the view of schizophrenia as a disorder of connectivity and of the synapse. Although attractive, such concepts are vague, and differentiating primary events from epiphenomena has been difficult. A way forward is provided by the recent identification of several putative susceptibility genes ( including neuregulin, dysbindin, COMT, DISC1, RGS4, GRM3, and G72). We discuss the evidence for these and other genes, along with what is known of their expression profiles and biological roles in brain and how these may be altered in schizophrenia. The evidence for several of the genes is now strong. However, for none, with the likely exception of COMT, has a causative allele or the mechanism by which it predisposes to schizophrenia been identified. Nevertheless, we speculate that the genes may all converge functionally upon schizophrenia risk via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry. NMDA receptor-mediated glutamate transmission may be especially implicated, though there are also direct and indirect links to dopamine and GABA signalling. Hence, there is a correspondence between the putative roles of the genes at the molecular and synaptic levels and the existing understanding of the disorder at the neural systems level. Characterization of a core molecular pathway and a 'genetic cytoarchitecture' would be a profound advance in understanding schizophrenia, and may have equally significant therapeutic implications. C1 Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Harrison, PJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Neurosci Bldg, Oxford OX3 7JX, England. EM paul.harrison@psych.ox.ac.uk; weinberd@intra.nimh.nih.gov NR 391 TC 1196 Z9 1233 U1 35 U2 317 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2005 VL 10 IS 1 BP 40 EP 68 DI 10.1038/sj.mp.4001558 PG 29 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 881RY UT WOS:000225888300005 PM 15263907 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI Systemic determinants of gene evolution and function SO MOLECULAR SYSTEMS BIOLOGY LA English DT Editorial Material ID PROTEIN-PROTEIN INTERACTIONS; INTERACTION NETWORK; GENOMIC ANALYSIS; DISPENSABILITY; ESSENTIALITY; MODULARITY; DEPENDENCE; NUMBER; RATES C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 18 TC 14 Z9 14 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PY 2005 VL 1 AR 2005.0021 DI 10.1038/msb4100029 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122RP UT WOS:000243244500022 PM 16729056 ER PT J AU Raben, N Fukuda, T Gilbert, AL de Jong, D Thurberg, BL Mattaliano, RJ Meikle, P Hopwood, JJ Nagashima, K Nagaraju, K Plotz, PH AF Raben, N Fukuda, T Gilbert, AL de Jong, D Thurberg, BL Mattaliano, RJ Meikle, P Hopwood, JJ Nagashima, K Nagaraju, K Plotz, PH TI Replacing acid alpha-glucosidase in Pompe disease: Recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers SO MOLECULAR THERAPY LA English DT Article DE transgenic knockout; tetracycline-controllable system; lysosomal trafficking; autophagy; enzyme replacement therapy; acid alpha-glucosidase; Pompe disease; lysosomal storage disease ID MANNOSE 6-PHOSPHATE RECEPTORS; LYSOSOMAL STORAGE DISEASES; REPLACEMENT THERAPY; MALTASE DEFICIENCY; KNOCKOUT MICE; RABBIT MILK; MAMMALIAN-CELLS; SKELETAL-MUSCLE; CLATHRIN; EXPRESSION AB Pompe disease (type II glycogen storage disease) is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-glucosidase (GAA) leading to the accumulation of glycogen in the lysosomes primarily in cardiac and skeletal muscle. The recombinant human GAA (rhGAA) is currently in clinical trials for enzyme replacement therapy of Pompe disease. Both clinical data and the results of preclinical studies in our knockout model of this disease show that rhGAA is much more effective in resolving the cardiomyopathy than the skeletal muscle myopathy. By contrast, another form of human GAA-transgenic enzyme constitutively produced in liver and secreted into the bloodstream of knockout mice (Gaa(-/-))-completely prevented both cardiac and skeletal muscle glycogen accumulation. In the experiments reported here, the transgenic enzyme was much less efficient when delivered to skeletal muscle after significant amounts of glycogen had already accumulated. Furthermore, the transgenic enzyme and the rhGAA have similar therapeutic effects, and both efficiently clear glycogen from cardiac muscle and type I muscle fibers, but not type II fibers. Low abundance of proteins involved in endocytosis and trafficking of lysosomal enzymes combined with increased autophagy in type II fibers may explain the resistance to therapy. C1 NIAMS, Ctr Clin, NIH, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. Genzyme Corp, Cell & Prot Therapeut R&D, Framingham, MA 01701 USA. Womens & Childrens Hosp, Dept Chem Pathol, Adelaide, SA 5006, Australia. Natl Canc Inst Federick, SAIC, Image Anal Lab, Ft Detrick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA. RP Raben, N (reprint author), NIAMS, Ctr Clin, NIH, Arthritis & Rheumatism Branch, 9N244,9000 Rockville Pike,Bldg 10, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov RI Meikle, Peter/B-4023-2009 NR 59 TC 85 Z9 89 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2005 VL 11 IS 1 BP 48 EP 56 DI 10.1016/j.ymthe.2004.09.017 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 906BI UT WOS:000227615100006 PM 15585405 ER PT J AU McInerney-Leo, A Hadley, DW Gwinn-Hardy, K Hardy, J AF McInerney-Leo, A Hadley, DW Gwinn-Hardy, K Hardy, J TI Genetic testing in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Editorial Material DE Parkinson's disease; genetic testing; parkin; alpha-synuclein ID EARLY-ONSET PARKINSONISM; MARKED DIURNAL FLUCTUATION; ALPHA-SYNUCLEIN PROMOTER; GTP CYCLOHYDROLASE-I; HUNTINGTONS-DISEASE; PARK6-LINKED PARKINSONISM; FAMILIAL AGGREGATION; MUTATIONS; RISK; ASSOCIATION AB Parkinson's disease (PD) is a common neurodegenerative disorder of adulthood characterized clinically by rigidity, bradykinesia, resting tremor, and postural instability. The annual incidence of PD ranges between 16 and 19 individuals per 100,000 (Twelves et al., Mov Disord 2003;18:19-31). Historically, PD has been commonly viewed as an idiopathic or environmentally triggered condition. However, as is true with most common conditions, there have been several families reported with PD who demonstrate a classic Mendelian pattern of inheritance. To date, nine genetic loci have been reported and four pathogenic genes have been identified: alpha-synuclein, parkin, DJ1, and PINK1. Families with alterations in these genes or linked sites demonstrate either recessive or dominant inheritance patterns and may have typical and/or atypical symptoms, with an age of onset extending from the second to the sixth decade. Commercial tests for parkin and alpha-synuclein mutations are now available. We predict that physicians, particularly neurologists, increasingly will be approached for information and referrals regarding genetic testing. To assist patients and their families, physicians will not only need to know when Such testing is likely to yield a meaningful result but also be aware of the possible social and emotional consequences of testing. The following is a review of what is currently known about the genetics of PD within this context. We discuss what is known about genetic testing for Huntington's disease, a well-described model for genetic testing in a neurodegenerative disorder. We explore the utility, appropriateness, and possible implications of genetic testing for diagnostic and presymptomatic purposes. (dagger)Published 2004 John Wiley Sons. C1 NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20952 USA. NINDS, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP McInerney-Leo, A (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20952 USA. EM amcinern@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Hardy, John/C-2451-2009; OI Gwinn, Katrina/0000-0002-8277-651X NR 77 TC 37 Z9 38 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2005 VL 20 IS 1 BP 1 EP 10 DI 10.1002/mds.20316 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 891EV UT WOS:000226565000001 PM 15503301 ER PT J AU Ogra, PL Mestecky, J Lamm, ME Strober, W McGhee, JR Bienenstock, J AF Ogra, Pearay L. Mestecky, Jiri Lamm, Michael E. Strober, Warren McGhee, Jerry R. Bienenstock, John BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Mucosal Immunology Third Edition Preface to the First Edition SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Ogra, Pearay L.] Childrens Hosp, Div Infect Dis, Buffalo, NY 14222 USA. [Mestecky, Jiri; McGhee, Jerry R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Mestecky, Jiri] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Lamm, Michael E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Bienenstock, John] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Bienenstock, John] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. RP Ogra, PL (reprint author), Childrens Hosp, Div Infect Dis, Buffalo, NY 14222 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP IX EP X DI 10.1016/B978-012491543-5/50000-0 PG 2 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400001 ER PT J AU Ogra, PL Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR AF Ogra, Pearay L. Mestecky, Jiri Lamm, Michael E. Strober, Warren Bienenstock, John McGhee, Jerry R. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Mucosal Immunology Third Edition Preface to the Second Edition SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Ogra, Pearay L.] Childrens Hosp, Div Infect Dis, Buffalo, NY 14222 USA. [Mestecky, Jiri; McGhee, Jerry R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Mestecky, Jiri] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Lamm, Michael E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Bienenstock, John] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Bienenstock, John] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. RP Ogra, PL (reprint author), Childrens Hosp, Div Infect Dis, Buffalo, NY 14222 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP XI EP XII DI 10.1016/B978-012491543-5/50001-2 PG 2 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400002 ER PT J AU Mestecky, J Bienenstock, J Lamm, ME Mayer, L McGhee, JR Strober, W AF Mestecky, Jiri Bienenstock, John Lamm, Michael E. Mayer, Lloyd McGhee, Jerry R. Strober, Warren BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Mucosal Immunology Third Edition Preface to the Third Edition SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Mestecky, Jiri; McGhee, Jerry R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Mestecky, Jiri] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Bienenstock, John] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Bienenstock, John] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Lamm, Michael E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Mayer, Lloyd] Mt Sinai Med Ctr, Ctr Immunol, New York, NY 10029 USA. [Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Mestecky, J (reprint author), Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP XIII EP XIII PG 1 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400003 ER PT J AU Mestecky, J Bienenstock, J McGhee, JR Lamm, ME Strober, W Cebra, JJ Mayer, L Ogra, PL AF Mestecky, Jiri Bienenstock, John McGhee, Jerry R. Lamm, Michael E. Strober, Warren Cebra, John J. Mayer, Lloyd Ogra, Pearay L. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Historical Aspects of Mucosal Immunology SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID SELECTIVE IGA DEFICIENCY; SECRETORY IMMUNOGLOBULIN-A; GLUTEN-SENSITIVE ENTEROPATHY; INTESTINAL EPITHELIAL-CELLS; CIRCULATING IMMUNE-COMPLEXES; VIRUS-INACTIVATING CAPACITY; INFLAMMATORY BOWEL-DISEASE; BRONCHIAL LYMPHOID-TISSUE; NORMAL MICROBIAL FLORA; GERM-FREE MICE C1 [Mestecky, Jiri; McGhee, Jerry R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Mestecky, Jiri] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Bienenstock, John] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Bienenstock, John] McMaster Univ, Dept Pathol, Hamilton, ON, Canada. [Bienenstock, John] McMaster Univ, Dept Mol Med, Hamilton, ON, Canada. [Lamm, Michael E.] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Strober, Warren] NIAID, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA. [Cebra, John J.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Mayer, Lloyd] Mt Sinai Med Ctr, Ctr Immunol, New York, NY 10029 USA. [Ogra, Pearay L.] SUNY Buffalo, Childrens Hosp, Div Infect Dis, Buffalo, NY 14260 USA. RP Mestecky, J (reprint author), Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. NR 301 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP XXXIII EP LVI DI 10.1016/B978-012491543-5/50004-8 PG 24 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400004 ER PT J AU Strober, W McGhee, JR AF Strober, Warren McGhee, Jerry R. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Inductive and Effector Tissues and Cells of the Mucosal Immune System: An Overview SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Editorial Material; Book Chapter C1 [Strober, Warren] NIAID, Mucosal Immunol Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [McGhee, Jerry R.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. RP Strober, W (reprint author), NIAID, Mucosal Immunol Sect, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP 371 EP 373 DI 10.1016/B978-012491543-5/50023-1 PG 3 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400023 ER PT J AU Kelsall, BL Leon, F Smythies, LE Smith, PD AF Kelsall, Brian L. Leon, Francisco Smythies, Lesley E. Smith, Phillip D. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Antigen Handling and Presentation by Mucosal Dendritic Cells and Macrophages SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID INFLAMMATORY-BOWEL-DISEASE; HUMAN PEYERS-PATCHES; TOLL-LIKE RECEPTORS; CD4(+) T-CELLS; EOSINOPHILIC AIRWAY INFLAMMATION; INTESTINAL EPITHELIAL-CELLS; COLONY-STIMULATING FACTOR; MESENTERIC LYMPH-NODES; MURINE SMALL-INTESTINE; MONONUCLEAR PHAGOCYTE SYSTEM C1 [Kelsall, Brian L.; Leon, Francisco] NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. [Smythies, Lesley E.; Smith, Phillip D.] Univ Alabama Birmingham, Dept Med, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Smith, Phillip D.] Vet Adm Med Ctr, Res Serv, Birmingham, AL USA. RP Kelsall, BL (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 335 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP 451 EP 485 DI 10.1016/B978-012491543-5/50030-9 PG 35 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400030 ER PT J AU Strober, W Fagarasan, S Lycke, N AF Strober, Warren Fagarasan, Sidonia Lycke, Nils BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI IgA B Cell Development SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID CLASS-SWITCH RECOMBINATION; GROWTH-FACTOR-BETA; IMMUNOGLOBULIN HEAVY-CHAIN; NF-KAPPA-B; INDUCED CYTIDINE DEAMINASE; MUCOSAL IMMUNE-SYSTEM; CD4(+) T-CELLS; THYMUS-EXPRESSED CHEMOKINE; CONSTANT-REGION GENE; MOUSE GERMLINE IG C1 [Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Fagarasan, Sidonia] RIKEN Res Ctr Allergy & Immunol, Lab Mucosal Immunol, Yokohama, Kanagawa, Japan. [Lycke, Nils] Univ Gothenburg, Dept Med Microbiol & Immunol, Gothenburg, Sweden. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 258 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP 583 EP 616 DI 10.1016/B978-012491543-5/50035-8 PG 34 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400035 ER PT J AU Murphy, BR AF Murphy, Brian R. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Mucosal Immunity to Viruses SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A-VIRUS; CYTOTOXIC T-LYMPHOCYTES; IGA MONOCLONAL-ANTIBODIES; RECOMBINANT VACCINIA VIRUSES; INTESTINAL LAMINA PROPRIA; ORAL POLIOVIRUS VACCINE; WASH IMMUNOGLOBULIN-G; ROTAVIRUS INFECTION; SENDAI-VIRUS C1 NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, BR (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 204 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP 799 EP 813 DI 10.1016/B978-012491543-5/50047-4 PG 15 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400047 ER PT J AU Smith, PD Wahl, SW AF Smith, Phillip D. Wahl, Sharon W. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Immunobiology of Mucosal HIV-1 Infection SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL LAMINA PROPRIA; GENITAL ULCER DISEASE; DENDRITIC CELLS; TYPE-1 INFECTION; LYMPHOID-TISSUE; ANTIRETROVIRAL THERAPY; SEXUAL TRANSMISSION C1 [Smith, Phillip D.] Univ Alabama Birmingham, Dept Med, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. [Smith, Phillip D.] Vet Adm Med Ctr, Res Serv, Birmingham, AL USA. [Wahl, Sharon W.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Smith, PD (reprint author), Univ Alabama Birmingham, Dept Med, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. NR 110 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP 1199 EP 1211 DI 10.1016/B978-012491543-5/50071-1 PG 13 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400071 ER PT J AU Strober, W Fuss, IJ AF Strober, Warren Fuss, Ivan J. BE Mestecky, J Lamm, ME Strober, W Bienenstock, J McGhee, JR Mayer, L TI Protein-Losing Enteropathies SO MUCOSAL IMMUNOLOGY, 3RD EDITION LA English DT Article; Book Chapter ID GROWTH-FACTOR-ALPHA; COMMON VARIABLE IMMUNODEFICIENCY; INFLAMMATORY-BOWEL-DISEASE; INTESTINAL LYMPHANGIECTASIA SECONDARY; TISSUE PLASMINOGEN ACTIVATOR; SYSTEMIC LUPUS-ERYTHEMATOSUS; MENETRIERS-DISEASE; EOSINOPHILIC GASTROENTERITIS; T-CELLS; INTERFERON-GAMMA C1 [Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Fuss, Ivan J.] NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 144 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045426-9 PY 2005 BP 1287 EP 1309 DI 10.1016/B978-012491543-5/50077-2 PG 23 WC Immunology SC Immunology GA BCR49 UT WOS:000311099400077 ER PT J AU Regenold, WT Phatak, P Makley, MJ Stone, R Kling, MA AF Regenold, WT Phatak, P Makley, MJ Stone, R Kling, MA TI Cerebrospinal fluid metabolic profiles differentiate MS types SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 9th Annual Meeting of Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY OCT 03, 2004 CL Toronto, CANADA SP Univ Maryland Sch Med, Natl Multiple Sclerosis Soc DE cerebrospinal fluid; glucose; lactate; metabolism; polyol; progression C1 Baltimore VA Med Ctr, Baltimore, MD USA. NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 0 TC 0 Z9 0 U1 1 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PY 2005 VL 11 IS 1 BP 123 EP 123 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 894ZZ UT WOS:000226831700049 ER PT J AU Morgen, K Crawford, ALT Stone, RD Martin, R Richert, ND Frank, JA McFarland, HF AF Morgen, K Crawford, ALT Stone, RD Martin, R Richert, ND Frank, JA McFarland, HF TI Contrast-enhanced MRI lesions during treatment with interferon beta-1b predict increase in T1 black hole volume in patients with relapsing-remitting multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE black holes; contrast-enhancing lesions; IFN beta-1b; relapsing-remitting MS ID SPIN-ECHO MRI; HYPOINTENSE LESIONS; MS AB T1 black holes (BH) have been found to represent focal areas of substantial central nervous system tissue damage in multiple sclerosis (MS) patients. We examined the development of T1 BH over a three-year period of treatment with interferon (IFN)beta-1b in a group of 20 patients with relapsing-remitting MS. The number of contrast-enhancing lesions (CEL) after one year of treatment predicted a change in the T1 BH volume in the following two years. In patients without CEL, the T1 BH volume remained stable, whereas it increased in patients with CEL. The occurrence of CEL in patients treated with IFN beta may indicate a heightened risk of accumulating T1 BH. C1 Univ Giessen, Dept Neurol, D-35385 Giessen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Bender Inst Neuroimaging, Giessen, Germany. Johns Hopkins Univ, Div Hematol Malignancies, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Morgen, K (reprint author), Univ Giessen, Dept Neurol, Steg 14, D-35385 Giessen, Germany. EM Katrin.Morgen@neuro.med.uni-giessen.de NR 10 TC 5 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PY 2005 VL 11 IS 2 BP 146 EP 148 DI 10.1191/1352458505ms1147oa PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 907KW UT WOS:000227717400004 PM 15794386 ER PT J AU Pulicken, M Bash, CN Costello, K Said, A Cuffari, C Wilterdink, JL Rogg, JM Mills, P Calabresi, PA AF Pulicken, M Bash, CN Costello, K Said, A Cuffari, C Wilterdink, JL Rogg, JM Mills, P Calabresi, PA TI Optimization of the safety and efficacy of interferon beta 1b and azathioprine combination therapy in multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE immunosuppression; MRI; therapy; 6-thioguanine; toxicity ID INFLAMMATORY-BOWEL-DISEASE; MS; BETA-1B; LESIONS; TRIAL AB We conducted an open-label pilot clinical trial to evaluate the safety and efficacy of adding oral azathioprine to the treatment regimen of 15 multiple sclerosis patients breaking through monotherapy with interferon beta-1b. There were no serious adverse events. Gastrointestinal side effects and leukopenia were the most common adverse events and limited dose escalation. There was a 65% reduction in the number of gadolinium-enhanced magnetic resonance imaging (MRI) lesions on combination therapy compared to the baseline values (P=0.003). A total WBC count less than 4800/mm(3) was the best predictor of MRI response. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Expt Imaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Brown Univ, Rhode Isl Hosp, Dept Clin Neurosci, Providence, RI 02903 USA. RP Calabresi, PA (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St, Baltimore, MD 21287 USA. EM calabresi@jhmi.edu NR 14 TC 21 Z9 23 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PY 2005 VL 11 IS 2 BP 169 EP 174 DI 10.1191/1352458505ms1141oa PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 907KW UT WOS:000227717400008 PM 15794390 ER PT J AU Klosek, MM Kuske, R AF Klosek, MM Kuske, R TI Multiscale analysis of stochastic delay differential equations SO MULTISCALE MODELING & SIMULATION LA English DT Article DE delay differential equation; stochastic resonance; amplitude equations; multiple scales ID DER-POL EQUATION; LYAPUNOV EXPONENTS; DYNAMICAL-SYSTEMS; HOPF-BIFURCATION; RESONANCE; NOISE; MODEL AB We apply multiscale analysis to stochastic delay differential equations, deriving approximate stochastic equations for the amplitudes of oscillatory solutions near critical delays of deterministic systems. Such models are particularly sensitive to noise when the system is near a critical point, which marks a transition to sustained oscillatory behavior in the deterministic system. In particular, we are interested in the case when the combined effects of the noise and the proximity to criticality amplify oscillations which would otherwise decay in the deterministic system. The derivation of reduced equations for the envelope of the oscillations provides an efficient analysis of the dynamics by separating the influence of the noise from the intrinsic oscillations over long time scales. We focus on two well-known problems: the linear stochastic delay differential equation and the logistic equation with delay. In addition to the envelope equations, the analysis identifies scaling relationships between small noise and the proximity of the bifurcation due to the delay which enhances the resonance of the noise with the intrinsic oscillations of the systems. C1 NCI, Lab Computat & Expt Biol, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. RP Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. EM klosek@nih.gov; rachel@math.ubc.ca NR 32 TC 17 Z9 18 U1 0 U2 2 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1540-3459 EI 1540-3467 J9 MULTISCALE MODEL SIM JI Multiscale Model. Simul. PY 2005 VL 3 IS 3 BP 706 EP 729 DI 10.1137/030601375 PG 24 WC Mathematics, Interdisciplinary Applications; Physics, Mathematical SC Mathematics; Physics GA 907UL UT WOS:000227743400008 ER PT S AU Lahiri, DK Chen, DM Lahiri, P Bondy, S Greig, NH AF Lahiri, DK Chen, DM Lahiri, P Bondy, S Greig, NH BE Kotwal, GJ Lahiri, DK TI Amyloid, cholinesterase, melatonin, and metals and their roles in aging and neurodegenerative diseases SO NATURAL PRODUCTS AND MOLECULAR THERAPY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Conference on Natural Products and Molecular Medicine CY JAN 13-15, 2005 CL Univ Cape Town, Cape Town, SOUTH AFRICA HO Univ Cape Town DE aging; acetylcholinesterase; amyloid; amyloid precursor protein; brain; cholinergic; cobalt; copper; diet; iron; melatonin; mercury; metalloprotease; metals; mouse; neurodegeneration; neuroprotection; synaptic proteins; zinc ID AGE-RELATED-CHANGES; NICOTINIC ACETYLCHOLINE-RECEPTORS; GENE-EXPRESSION PROFILE; RAT VAS-DEFERENS; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; PINEAL-GLAND; CEREBRAL-CORTEX; NEUROBLASTOMA-CELLS; CALORIC RESTRICTION AB The aging brain shows selective neurochemical changes involving several neural cell populations. Increased brain metal levels have been associated with normal aging and a variety of diseases, including Alzheimer's disease (AD). Melatonin levels are decreased in aging, particularly in AD subjects. The loss of melatonin, which is synthesized by the pineal gland, together with the degeneration of cholinergic neurons of the basal forebrain and the deposition of aggregated proteins, such as the amyloid beta peptides (A beta), are believed to contribute to the development of cognitive symptoms of dementia. Aging and its variants, such as AD, should be viewed as the result of multiple "hits," including alterations in the levels of A beta, metals, cholinesterase enzymes, and neuronal gene expression. Herein, we present evidence in support of this theory, based on several studies. We discuss melatonin's neuroprotective function, which plays an important role in aging, prolongation of life span, and health in the aged individual. It interacts with metals and, in some cases, neutralizes their toxic effects. Dietary supplementation of melatonin restores its age-related loss. In mice, an elevated brain melatonin significantly reduced levels of potentially toxic A beta peptides. Thus, compensation of melatonin loss in aging by dietary supplementation could well be beneficial in terms of reducing metal-induced toxicity, lipid peroxidation, and losses in cholinergic signaling. We propose that certain cholinesterase inhibitors and the NMDA partial antagonist memantine, which are FDA-approved drugs for AD and useful to boost central nervous system functioning, can be made more effective by their combination with melatonin or other neuroprotectants. Herein, we highlight studies elucidating the role of the amyloid pathway, metals, melatonin, and the cholinergic system in the context of aging and AD. Finally, melatonin is present in edible plants and walnuts, and consuming foodstuffs containing melatonin would be beneficial by enhancing the antioxidative capacity of the organisms. C1 Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. Banaras Hindu Univ, Womens Coll, Dept Chem, Varanasi 221005, Uttar Pradesh, India. Univ Calif Irvine, Dept Community & Environm Med, Irvine, CA 92697 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, 791 Union Dr, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu; dlahiri@iupui.edu FU NIA NIH HHS [AG 16794, AG 18379, AG 18884]; NIEHS NIH HHS [ES 7992] NR 81 TC 28 Z9 29 U1 2 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-594-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1056 BP 430 EP 449 DI 10.1196/annals.1352.008 PG 20 WC Biochemistry & Molecular Biology; Integrative & Complementary Medicine; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Integrative & Complementary Medicine; Research & Experimental Medicine; Science & Technology - Other Topics GA BDU43 UT WOS:000235433100036 PM 16387707 ER PT J AU Conrads, TP Veenstra, TD AF Conrads, TP Veenstra, TD TI An enriched look at tyrosine phosphorylation SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Conrads, TP (reprint author), NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM conrads@ncifcrf.gov; veenstra@ncifcrf.gov NR 6 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2005 VL 23 IS 1 BP 36 EP 37 DI 10.1038/nbt0105-36 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 885ZK UT WOS:000226195700019 PM 15637616 ER PT J AU Khil, PP Camerini-Otero, RD AF Khil, PP Camerini-Otero, RD TI Explaining the X-linkage bias of placentally expressed genes - Reply SO NATURE GENETICS LA English DT Letter ID SEX-CHROMOSOMES; EVOLUTION; MOUSE; INACTIVATION; SELECTION C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, 5 Mem Dr, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov OI Khil, Pavel/0000-0002-4903-8777 NR 9 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2005 VL 37 IS 1 BP 3 EP 4 DI 10.1038/ng0105-3b PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 883FX UT WOS:000225997500004 ER PT J AU Turner, JMA Mahadevaiah, SK Fernandez-Capetillo, O Nussenzweig, A Xu, XL Deng, CX Burgoyne, PS AF Turner, JMA Mahadevaiah, SK Fernandez-Capetillo, O Nussenzweig, A Xu, XL Deng, CX Burgoyne, PS TI Silencing of unsynapsed meiotic chromosomes in the mouse SO NATURE GENETICS LA English DT Article ID X-CHROMOSOME; SYNAPTONEMAL COMPLEXES; MALE-FERTILITY; MICE; CELLS; DNA; MEIOSIS; BRCA1; PROTEIN; SPERMATOGENESIS AB In Neurospora, DNA unpaired in meiosis both is silenced and induces silencing of all DNA homologous to it. This process, called meiotic silencing by unpaired DNA, is thought to protect the host genome from invasion by transposable elements. We now show that silencing of unpaired (unsynapsed) chromosome regions also takes place in the mouse during both male and female meiosis. The tumor suppressor protein BRCA1 is implicated in this silencing, mirroring its role in the meiotic silencing of the X and Y chromosomes in normal male meiosis. These findings impact on the interpretation of the relationship between synaptic errors and sterility in mammals and extend our understanding of the biology of Brca1. C1 Natl Inst Med Res, MRC, Div Stem Cell Res & Dev Genet, London NW7 1AA, England. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Turner, JMA (reprint author), Natl Inst Med Res, MRC, Div Stem Cell Res & Dev Genet, Mill Hill, London NW7 1AA, England. EM jturner@nimr.mrc.ac.uk RI Fernandez-Capetillo, Oscar/H-3508-2015; deng, chuxia/N-6713-2016 OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885; FU Medical Research Council [MC_U117532009, MC_U117588498] NR 39 TC 326 Z9 343 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2005 VL 37 IS 1 BP 41 EP 47 DI 10.1038/ng1484 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 883FX UT WOS:000225997500019 PM 15580272 ER PT J AU Oleksiak, MF Roach, JL Crawford, DL AF Oleksiak, MF Roach, JL Crawford, DL TI Natural variation in cardiac metabolism and gene expression in Fundulus heteroclitus SO NATURE GENETICS LA English DT Article ID GLYCOLYTIC ENZYME EXPRESSION; PATTERNS; POPULATIONS; VARIANCE; YEAST; BLOOD AB Individual variation in gene expression is important for evolutionary adaptation(1,2) and susceptibility to diseases and pathologies(3,4). In this study, we address the functional importance of this variation by comparing cardiac metabolism to patterns of mRNA expression using microarrays. There is extensive variation in both cardiac metabolism and the expression of metabolic genes among individuals of the teleost fish Fundulus heteroclitus from natural outbred populations raised in a common environment: metabolism differed among individuals by a factor of more than 2, and expression levels of 94% of genes were significantly different (P < 0.01) between individuals in a population. This unexpectedly high variation in metabolic gene expression explains much of the variation in metabolism, suggesting that it is biologically relevant. The patterns of gene expression that are most important in explaining cardiac metabolism differ between groups of individuals. Apparently, the variation in metabolism seems to be related to different patterns of gene expression in the different groups of individuals. The magnitude of differences in gene expression in these groups is not important; large changes in expression have no greater predictive value than small changes. These data suggest that variation in physiological performance is related to the subtle variation in gene expression and that this relationship differs among individuals. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Crawford, DL (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS,Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. EM dcrawford@rsmas.miami.edu FU NHLBI NIH HHS [R01 HL065470-03, R01 HL065470-01A2, R01 HL065470-02] NR 25 TC 127 Z9 131 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2005 VL 37 IS 1 BP 67 EP 72 DI 10.1038/ng1483 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 883FX UT WOS:000225997500022 PM 15568023 ER PT J AU Roca, AL Georgiadis, N O'Brien, SJ AF Roca, AL Georgiadis, N O'Brien, SJ TI Cytonuclear genomic dissociation in African elephant species SO NATURE GENETICS LA English DT Article ID MITOCHONDRIAL; DNA; NUCLEAR; POPULATIONS; UGANDA; LOCI AB African forest and savanna elephants are distinct species separated by a hybrid zone(1-4). Because hybridization can affect the systematic and conservation status of populations, we examined gene flow between forest and savanna elephants at 21 African locations. We detected cytonuclear dissociation, indicative of different evolutionary histories for nuclear and mitochondrial genomes. Both paternally (n = 205 males) and biparentally (n = 2, 123 X-chromosome segments) inherited gene sequences indicated that there was deep genetic separation between forest and savanna elephants. Yet in some savanna locales distant from present-day forest habitats, many individuals with savanna-specific nuclear genotypes carried maternally transmitted forest elephant mitochondrial DNA. This extreme cytonuclear dissociation implies that there were ancient episodes of hybridization between forest females and savanna males, which are larger and reproductively dominant to forest or hybrid males(1,2,5-7). Recurrent backcrossing of female hybrids to savanna bulls replaced the forest nuclear genome. The persistence of residual forest elephant mitochondria in savanna elephant herds renders evolutionary interpretations based on mitochondrial DNA alone misleading and preserves a genomic record of ancient habitat changes. C1 SAIC Frederick, Basic Res Program, Lab Genom Divers, Frederick, MD 21702 USA. Mpala Res Ctr, Nanyuki, Kenya. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), SAIC Frederick, Basic Res Program, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@ncifcrf.gov NR 30 TC 132 Z9 136 U1 5 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2005 VL 37 IS 1 BP 96 EP 100 DI 10.1038/ng1485 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 883FX UT WOS:000225997500027 PM 15592471 ER PT J AU Barda-Saad, M Braiman, A Titerence, R Bunnell, SC Barr, VA Samelson, LE AF Barda-Saad, M Braiman, A Titerence, R Bunnell, SC Barr, VA Samelson, LE TI Dynamic molecular interactions linking the T cell antigen receptor to the actin cytoskeleton SO NATURE IMMUNOLOGY LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; APC CONTACT SITE; IMMUNOLOGICAL SYNAPSE; SYNDROME PROTEIN; SIGNAL-TRANSDUCTION; ARP2/3 COMPLEX; ACTIVATION; LAT; RECRUITMENT; WASP AB T cell receptor (TCR) engagement leads to actin polymerization at the site of T cell contact with antigen-presenting cells. Here we have studied the dynamic activity of proteins involved in regulating actin polymerization in live T cells after activation. Two such adaptor proteins, Nck and the Wiskott-Aldrich syndrome protein (WASp), were recruited to the TCR during initial T cell activation, where they colocalized with the tyrosine kinase Zap70. The recruitment of Nck and WASp depended on TCR-induced tyrosine phosphorylation and the LAT and SLP-76 adaptors. Nck and WASp migrated peripherally and accumulated at an actin-rich circumferential ring. Thus, actin polymerization regulated by the TCR begins at the TCR. Molecules recruited to the TCR regulate actin polymerization and this process drives plasma membrane movement and cellular spreading. C1 NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov RI Braiman, Alex/F-2179-2012 OI Braiman, Alex/0000-0003-2802-1148 NR 43 TC 193 Z9 198 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2005 VL 6 IS 1 BP 80 EP 89 DI 10.1038/ni1143 PG 10 WC Immunology SC Immunology GA 881SA UT WOS:000225888500021 PM 15558067 ER PT J AU McClain, MT Heinlen, LD Dennis, GJ Roebuck, J Harley, JB James, JA AF McClain, MT Heinlen, LD Dennis, GJ Roebuck, J Harley, JB James, JA TI Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry SO NATURE MEDICINE LA English DT Article ID EPSTEIN-BARR-VIRUS; B-CELL EPITOPES; SM B/B'; ERYTHEMATOSUS; AUTOANTIBODIES; AUTOANTIGENS; ANTIBODIES; INFECTION; RESPONSES; PEPTIDES AB The origins of autoimmunity in systemic lupus erythematosus (SLE) are thought to involve both genetic and environmental factors. To identify environmental agents that could potentially incite autoimmunity, we have traced the autoantibody response in human SLE back in time, prior to clinical disease onset, and identified the initial autoantigenic epitope for some lupus patients positive for antibodies to 60 kDa Ro. This initial epitope directly cross-reacts with a peptide from the latent viral protein Epstein-Barr virus nuclear antigen-1 (EBNA-1). Animals immunized with either the first epitope of 60 kDa Ro or the cross-reactive EBNA-1 epitope progressively develop autoantibodies binding multiple epitopes of Ro and spliceosomal autoantigens. They eventually acquire clinical symptoms of lupus such as leukopenia, thrombocytopenia and renal dysfunction. These data support the hypothesis that some humoral autoimmunity in human lupus arises through molecular mimicry between EBNA-1 and lupus autoantigens and provide further evidence to suspect an etiologic role for Epstein-Barr virus in SLE. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. Dept Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. Walter Reed Army Med Ctr, Dept Rheumatol, Washington, DC 20307 USA. NIAMSD, Bethesda, MD 20892 USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM jamesj@omrf.ouhsc.edu FU NCRR NIH HHS [RR14467, RR15577, RR20143]; NIAID NIH HHS [AI24717, AI31584, AI47575, AI53747, AI54117]; NIAMS NIH HHS [AR42460, AR45084, AR45231, AR45451, AR48045, AR48940]; NIDCR NIH HHS [DE015223] NR 30 TC 202 Z9 212 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2005 VL 11 IS 1 BP 85 EP 89 DI 10.1038/nm1167 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 884ZJ UT WOS:000226124900037 PM 15619631 ER PT J AU Boshoff, HIM Barry, CE AF Boshoff, HIM Barry, CE TI Tuberculosis - Metabolism and respiration in the absence of growth SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID MYCOBACTERIUM-BOVIS BCG; MICROBIAL ENUMERATION TECHNIQUE; ANAEROBIC NITRATE REDUCTASE; COMPLETE GENOME SEQUENCE; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; STATIONARY-PHASE; HYPOXIC RESPONSE; NONREPLICATING PERSISTENCE; MURINE TUBERCULOSIS AB Human tuberculosis is a complex disease caused by bacterial populations that are located in discrete lesions (microenvironments) in a single host. Some of these microenvironments are conducive to replication, whereas others restrict bacterial growth without necessarily sterilizing the infecting microorganisms. The physical and biochemical milieu in these lesions is poorly defined. None of the existing animal models for tuberculosis ( except perhaps non-human primates) reproduce the diversity of disease progression that is seen in humans. Nonetheless, transcriptomics and studies using bacterial mutants have led to testable hypotheses about metabolic functions that are essential for viability in the absence of replication. A complete picture of bacterial metabolism must balance reducing equivalents while maintaining an energized membrane and basic cellular processes. C1 NIAID, TB Res Sect, LIG, NIH, Rockville, MD 20852 USA. RP Boshoff, HIM (reprint author), NIAID, TB Res Sect, LIG, NIH, Twinbrook 2,Room 239,12441 Parklawn Dr, Rockville, MD 20852 USA. EM hboshoff@niaid.nih.gov; clifton_barry@nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 90 TC 247 Z9 262 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD JAN PY 2005 VL 3 IS 1 BP 70 EP 80 DI 10.1038/nrmicro1065 PG 11 WC Microbiology SC Microbiology GA 883PF UT WOS:000226024900016 PM 15608701 ER PT J AU Sengupta, S Harris, CC AF Sengupta, S Harris, CC TI p53: Traffic cop at the crossroads of DNA repair and recombination SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID NUCLEOTIDE EXCISION-REPAIR; STRAND BREAK REPAIR; DEPENDENT PROTEIN-KINASE; TUMOR-SUPPRESSOR P53; INTRACHROMOSOMAL HOMOLOGOUS RECOMBINATION; DAMAGE-INDUCED PHOSPHORYLATION; WERNER-SYNDROME HELICASE; BLOOMS-SYNDROME HELICASE; GLOBAL GENOMIC REPAIR; S-PHASE ARREST AB p53 mutants that lack DNA-binding activities, and therefore, transcriptional activities, are among the most common mutations in human cancer. Recently, a new role for p53 has come to light, as the tumour suppressor also functions in DNA repair and recombination. In cooperation with its function in transcription, the transcription-independent roles of p53 contribute to the control and efficiency of DNA repair and recombination. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Immunol, New Delhi 110067, India. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov OI Sengupta, Sagar/0000-0002-6365-1770 NR 144 TC 306 Z9 321 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JAN PY 2005 VL 6 IS 1 BP 44 EP 55 DI 10.1038/nrm1546 PG 12 WC Cell Biology SC Cell Biology GA 884TM UT WOS:000226109300013 PM 15688066 ER PT J AU Garcia-Diaz, M Bebenek, K Krahn, JM Kunkel, TA Pedersen, LC AF Garcia-Diaz, M Bebenek, K Krahn, JM Kunkel, TA Pedersen, LC TI A closed conformation for the Pol lambda catalytic cycle SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DNA-POLYMERASE-LAMBDA; CRYSTAL-STRUCTURES; MECHANISM; COMPLEXES; REPAIR AB Pollambda is a family X member believed to fill short gaps during DNA repair. Here we report crystal structures of Pollambda representing three steps in filling a single-nucleotide gap. These structures indicate that, unlike other DNA polymerases, Pollambda does not undergo large subdomain movements during catalysis, and they provide a clear characterization of the geometry and stereochemistry of the in-line nucleotidyl transfer reaction. C1 NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov NR 13 TC 105 Z9 105 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2005 VL 12 IS 1 BP 97 EP 98 DI 10.1038/nsmb876 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 886GU UT WOS:000226215700018 PM 15608652 ER PT J AU Sampson, JH Reardon, DA Friedman, AH Friedman, HS Coleman, RE McLendon, RE Pastan, I Bigner, DD AF Sampson, JH Reardon, DA Friedman, AH Friedman, HS Coleman, RE McLendon, RE Pastan, I Bigner, DD TI Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: Case study SO NEURO-ONCOLOGY LA English DT Article ID MALIGNANT BRAIN-TUMORS; PHASE-I TRIAL; RAT MODEL; MICROINFUSION; GLIOMAS; IMMUNOTOXIN; EXPRESSION; CHEMOTHERAPY; TF-CRM107; EXOTOXIN AB Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to transforming growth factor (TGF)-alpha. TGF-alpha binds with high affinity to the epidermal growth factor receptor, which is uniformly overexpressed in malignant gliomas, often because of gene amplification. Prior to therapy with TP-38, the patient described here was completely refractory to multiple other therapies, with radiographic and pathologic evidence of tumor progression. After therapy, she improved clinically, was weaned off steroids and anticonvulsants, and experienced a progressive decrease in enhancing tumor volume. Despite multiple prior recurrences, she has not progressed for >43 months after TP-38 therapy. Small remaining areas of enhancement demonstrate no evidence of tumor histologically and are hypometabolic on positron emission tomography. This report describes a dramatic and sustained clinical and radiographic response in a patient with a bifrontal glioblastoma multiforme treated with intratumoral infusion of a novel targeted toxin, C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. NIH, Bethesda, MD 20892 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Box 3050,220 Sands Bldg,Res Dr, Durham, NC 27710 USA. EM john.sampson@duke.edu RI Coleman, Ralph/A-7865-2009 FU NCI NIH HHS [5R01-CA97611-05, R01 CA097611]; NCRR NIH HHS [K23 RR016065, K23 RR16065] NR 26 TC 36 Z9 36 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2005 VL 7 IS 1 BP 90 EP 96 DI 10.1215/S1152851703000589 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 894SY UT WOS:000226813100010 PM 15701286 ER PT J AU Cabin, DE Gispert-Sanchez, S Murphy, D Auburger, G Myers, RR Nussbaum, RL AF Cabin, DE Gispert-Sanchez, S Murphy, D Auburger, G Myers, RR Nussbaum, RL TI Exacerbated synucleinopathy in mice expressing A53T SNCA on a Snca null background SO NEUROBIOLOGY OF AGING LA English DT Article DE Parkinson's disease; alpha-synuclein; mouse models; neurodegeneration; Wallerian degeneration; pale bodies ID HUMAN ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; TRANSGENIC MICE; NEURODEGENERATIVE DISEASE; WILD-TYPE; MOUSE; MUTATION; NEUROTOXICITY; ACCUMULATION; AGGREGATION AB alpha-Synuclein is a major component of Lewy bodies, neuronal inclusions diagnostic for Parkinson's disease (PD). While an Ala53Thr mutation in alpha-synuclein can cause PD in humans, in mice the wildtype residue at position 53 is threonine, indicating that mice are either too short-lived to develop PD, or are protected by the six other amino acid differences between the proteins in these two species. Mice carrying an Ala53Thr human SNCA transgene driven by the mouse prion promoter show a mild movement disorder and only rarely develop severe pathology by 2 years of age. To determine whether the presence of mouse alpha-synuclein affects the pathogenicity of the human protein, the transgene was crossed into mice lacking endogenous alpha-synuclein. Mice that express only human alpha-synuclein developed a neuronopathy characterized by limb weakness and paralysis with onset beginning at 16 months of age. The neuronopathy is probably due to high levels of expression of the transgene in the ventral spinal cord leading to motor neuron damage and Wallerian degeneration of the ventral roots. These data suggest mouse alpha-synuclein is protective against the deleterious effects of the human mutant protein. (C) 2004 Elsevier Inc. All rights reserved. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Hosp, Inst Expt Neurobiol, Frankfurt, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. San Diego VA Healthcare Syst, San Diego, CA USA. Univ Hosp, Neurol Clin, Frankfurt, Germany. RP Nussbaum, RL (reprint author), NHGRI, NIH, 49 Convent Dr,Bldg 49,Room 4A72, Bethesda, MD 20892 USA. EM rlnuss@mail.nih.gov NR 34 TC 43 Z9 43 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN PY 2005 VL 26 IS 1 BP 25 EP 35 DI 10.1016/j.neurobiolaging.2004.02.026 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 885TA UT WOS:000226178600004 PM 15585343 ER PT J AU Leeds, P Leng, Y Chalecka-Franaszek, E Chuang, DM AF Leeds, P Leng, Y Chalecka-Franaszek, E Chuang, DM TI Neurotrophins protect against cytosine arabinoside-induced apoptosis of immature rat cerebellar neurons SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE neurotrophins; cerebellar granule cell; AraC neurotoxicity; PI 3-kinase/Akt; neurotoxicity; NIAPK; neuroprotection ID NERVE GROWTH-FACTOR; METHYL-D-ASPARTATE; SIGNAL-REGULATED KINASE; GRANULE NEURONS; CELL-DEATH; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; PHOSPHATIDYLINOSITOL 3-KINASE; SYMPATHETIC NEURONS; BCL-2 EXPRESSION; LEUKEMIA-CELLS AB Neurotrophin-induced neuroprotection against apoptosis was investigated using immature cultured cerebellar granule celk (CGC) from newborn rat pups. Apoptotic cell death induced by treatment with cytosine arabinoside (AraC) was confirmed by DNA fragmentation and quantified by cell survival assays. AraC was most effective in inducing apoptosis when added to CGC on the day of culture preparation. while less or no effect was observed when added at 24 or 48 h after plating. respectively. Pretreatment of CGC cultures for 24 h with brain-derived neurotrophic factor (BDNF) or neurotrophin-4 (NT-4), but not neurotrophin-3 (NT-3). robustly protected against AraC neurotoxicity. K252a. an inhibitor of the tropomyosin-related kinase (Trk) tyrosine kinase receptor family which showed no toxicity by itself, blocked BUNT protection of AraC-induced apoptosis in a concentration-dependent manner. Neither protein kinase C activation nor inhibition mimicked or affected BDNF protection against AraC neurotoxicity. BDNF, but not NT-3. treatment of immature CGC caused a marked. but transient activation of Akt through phosphatidylinositol (PI) 3-kinase. The neuroprotective effects of BDNF were suppressed by pretreatment with LY 294002 (a PI 3-kinase inhibitor). BDNF neuroprotection was also preceded by activation of mitogen activated protein kinase (MAPK) and suppressed by two MAPK/ERK (MEK)-selective inhibitors, PD 98059 and U-0126. Moreover. inhibitors of PI 3-kinase and MEK potentiated AraC-induced neurotoxicity. These results show that neurotrophins protect against AraC-induced apoptosis, at least in part, through TrKB-mediated activation of the PI 3-kinase/Akt and MEK signaling pathways. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov NR 78 TC 34 Z9 40 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JAN PY 2005 VL 46 IS 1 BP 61 EP 72 DI 10.1016/j.neuint.2004.07.001 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 886XO UT WOS:000226266600007 PM 15567516 ER PT J AU Sun, XY Beglopoulos, V Mattson, MP Shen, J AF Sun, Xiaoyan Beglopoulos, Vassilios Mattson, Mark P. Shen, Jie TI Hippocampal Spatial Memory Impairments Caused by the Familial Alzheimer's Disease-Linked Presenilin 1 M146V Mutation SO NEURODEGENERATIVE DISEASES LA English DT Article DE Knock-in mouse model; Brain; Water maze task; gamma-Secretase; Spatial memory; Hippocampus; Presenilin AB Mutations in presenilins (PS) 1 and 2 are the major cause of familial Alzheimer's disease. Conditional inactivation of PS1 in the mouse postnatal forebrain leads to mild deficits in spatial learning and memory, whereas inactivation of both PS1 and PS2 results in severe memory and synaptic plasticity impairments, followed by progressive and substantial neurodegeneration. Here we investigate the effect of a familial Alzheimer's disease-linked PS1 missense mutation using knock-in (KI) mice, in which the wild-type PS1 allele is replaced with the M146V mutant allele. In the Morris water maze task, PS1 KI mice at 3 months of age exhibit reduced quadrant occupancy and platform crossing in the probe trial after 6 days of training, though their performance was normal in the probe trial after 12 days of training. By the age of 9 months, even after 12 days of training, PS1 homozygous KI mice still exhibit reduced platform crossing in the post-training probe trial. ELISA analysis revealed a selective increase in cortical levels of beta-amyloid 42 in PS1 KI mice, whereas production of beta-amyloid 40 was normal. Histological and quantitative real-time RT-PCR analyses showed normal gross hippocampal morphology and unaltered expression of three genes involved in inflammatory responses in PS1 KI mice. These results show hippocampal spatial memory impairments caused by the PS1 M146V mutation and age-related deterioration of the memory impairment, suggesting that PS1 KI mice are a valuable model system for the study of memory loss in AD. Copyright (c) 2005 S. Karger AG, Basel C1 [Sun, Xiaoyan; Beglopoulos, Vassilios; Shen, Jie] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Program Neurosci, Boston, MA 02115 USA. [Mattson, Mark P.] NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Shen, J (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Program Neurosci, Harvard New Res Bldg 636E,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM jshen@rics.bwh.harvard.edu FU R01 grant from the National Institute of Neurological Disorders and Stroke [NS041783] FX We thank W. Cheng for assistance. This work was supported by an R01 grant (NS041783) from the National Institute of Neurological Disorders and Stroke. NR 28 TC 22 Z9 22 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2005 VL 2 IS 1 BP 6 EP 15 DI 10.1159/000086426 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V24IJ UT WOS:000208403800002 PM 16908998 ER PT J AU Kamel, F Umbach, DM Hu, H Munsat, TL Shefner, JM Taylor, JA Sandler, DP AF Kamel, F. Umbach, D. M. Hu, H. Munsat, T. L. Shefner, J. M. Taylor, J. A. Sandler, D. P. TI Lead Exposure as a Risk Factor for Amyotrophic Lateral Sclerosis SO NEURODEGENERATIVE DISEASES LA English DT Article DE Amyotrophic lateral sclerosis; Epidemiology; Lead exposure; Environment AB Background: The etiology of amyotrophic lateral sclerosis (ALS) likely involves an environmental component. We qualitatively assessed literature on ALS and lead exposure. Problems of study design make case reports and studies of lead in blood or tissues difficult to interpret. Most previous case-control studies found an association of ALS with self-reported occupational exposure to lead, with increased risks of 2- to 1 4-fold. However, these results may have been affected by recall bias. Objective: To address inconsistencies among published reports, we used both lead biomarkers and interview data to assess lead exposure, and we evaluated the role of genetic susceptibility to lead. Methods: We conducted a case-control study in New England in 1993-1996 with 109 ALS cases and 256 population-based controls. We measured blood and bone lead levels, the latter using X-ray fluorescence, and interviewed participants regarding sources of lead exposure. Results: In our study, ALS was associated with self-reported occupational lead exposure, with a dose response for cumulative days of exposure. ALS was also associated with blood and bone lead levels, with a 1.9-fold increase in risk for each mu g/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk. Conclusion: These results, together with previous studies, suggest that lead exposure plays a role in the etiology of ALS. An increase in mobilization of lead from bone into blood may play a role in the acute onset of disease. Copyright (C) 2005 S. Karger AG, Basel C1 [Kamel, F.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Hu, H.; Sandler, D. P.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Hu, H.; Sandler, D. P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Munsat, T. L.] Tufts Univ New England Med Ctr, Cambridge, MA USA. [Shefner, J. M.] SUNY Upstate Med Univ, Syracuse, NY USA. RP Kamel, F (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM kamel@mail.nih.gov OI Kamel, Freya/0000-0001-5052-6615; taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018 FU NIH, National Institute of Environmental Health Sciences FX Lyle Lansdell and Karen Catoe conducted the study; Dr. Terry Lehman analyzed ALAD polymorphisms, and Dr. Michael Bohlig and Dr. Larry Park provided statistical programming support. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 57 TC 53 Z9 54 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2005 VL 2 IS 3-4 BP 195 EP 201 DI 10.1159/000089625 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V24IL UT WOS:000208404000011 PM 16909025 ER PT J AU Papassotiropoulos, A Lambert, JC Wavrant-De Vrieze, F Wollmer, MA von der Kammer, H Streffer, JR Maddalena, A Huynh, KD Wolleb, S Lutjohann, D Schneider, B Thal, DR Grimaldi, LME Tsolaki, M Kapaki, E Ravid, R Konietzko, U Hegi, T Pasch, T Jung, H Braak, H Amouyel, P Rogaev, EI Hardy, J Hock, C Nitsch, RM AF Papassotiropoulos, Andreas Lambert, Jean-Charles Wavrant-De Vrieze, Fabienne Wollmer, M. Axel von der Kammer, Heinz Streffer, Johannes R. Maddalena, Alessia Huynh, Kim-Dung Wolleb, Sibylle Luetjohann, Dieter Schneider, Brigitte Thal, Dietmar R. Grimaldi, Luigi M. E. Tsolaki, Magdalini Kapaki, Elisabeth Ravid, Rivka Konietzko, Uwe Hegi, Thomas Pasch, Thomas Jung, Hans Braak, Heiko Amouyel, Philippe Rogaev, Evgeny I. Hardy, John Hock, Christoph Nitsch, Roger M. TI Cholesterol 25-Hydroxylase on Chromosome 10q Is a Susceptibility Gene for Sporadic Alzheimer's Disease SO NEURODEGENERATIVE DISEASES LA English DT Article DE beta-Amyloid; Cholesterol; Cholesterol 25-hydroxylase; Dementia; Genetic association; Lathosterol; Susceptibility gene; Tau AB Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25H chi 2, CH25H chi 3 and CH25H chi 4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25H chi 4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25H chi 4 and CH25H chi 3 haplotypes, whereas no A beta deposits were present in CH25H chi 2 carriers. Together, these results are compatible with a role of CH25H chi 4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition. Copyright (C) 2005 S. Karger AG, Basel C1 [Papassotiropoulos, Andreas; Wollmer, M. Axel; Streffer, Johannes R.; Maddalena, Alessia; Huynh, Kim-Dung; Wolleb, Sibylle; Konietzko, Uwe; Hock, Christoph; Nitsch, Roger M.] Univ Zurich, Div Psychiat Res, CH-8029 Zurich, Switzerland. [Hegi, Thomas; Pasch, Thomas] Univ Zurich, Inst Anesthesiol, CH-8029 Zurich, Switzerland. [Jung, Hans] Univ Zurich, Dept Neurol, CH-8029 Zurich, Switzerland. [Lambert, Jean-Charles; Amouyel, Philippe] Inst Pasteur, INSERM, U508, F-59019 Lille, France. [Wavrant-De Vrieze, Fabienne; Hardy, John] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Rogaev, Evgeny I.] Univ Massachusetts, Sch Med, Dept Psychiat, Brudnick Neuropsychiat Res Inst, Worcester, MA 01655 USA. [von der Kammer, Heinz] Evotec Neurosci, Hamburg, Germany. [Luetjohann, Dieter; Schneider, Brigitte] Univ Bonn, Inst Clin Pharmacol, Bonn, Germany. [Thal, Dietmar R.] Univ Bonn, Med Ctr, Inst Neuropathol, Bonn, Germany. [Braak, Heiko] Goethe Univ Frankfurt, Inst Clin Neuroanat, Frankfurt, Germany. [Grimaldi, Luigi M. E.] AUSL n 2, Dept Neurosci, Caltanissetta, Italy. [Tsolaki, Magdalini] Aristotle Univ Thessaloniki, Dept Neurol 3, GR-54006 Thessaloniki, Greece. [Kapaki, Elisabeth] Univ Athens, Sch Med, Aeginition Hosp, Dept Neurol, GR-11527 Athens, Greece. [Ravid, Rivka] Netherlands Brain Bank, Amsterdam, Netherlands. RP Papassotiropoulos, A (reprint author), Univ Zurich, Div Psychiat Res, Lenggstr 31, CH-8029 Zurich, Switzerland. EM papas@bli.unizh.ch RI Wollmer, Marc /B-5038-2009; lambert, jean-charles/F-8787-2013; Lambert, jean-charles/A-9553-2014 OI Lambert, jean-charles/0000-0003-0829-7817 FU Swiss Science National Foundation [32-65869.01, PP00B-68859]; Roche Research Foundation [22-2001]; EMDO Stiftung; National Center for Competence in Research 'Neuronal Plasticity and Repair'; EU APOPIS Program [LSHM-CT-2003-503330] FX We thank Ms. Esmeralda Garcia, Ms. Christin Wilde, Mrs. Andrea Walter, and Ms. Estelle Obrist for patient care and sampling. This work was supported in parts by grants from the Swiss Science National Foundation (32-65869.01 and PP00B-68859), the Roche Research Foundation (22-2001) and the EMDO Stiftung to A.P., the National Center for Competence in Research 'Neuronal Plasticity and Repair', and by the EU APOPIS Program (contract LSHM-CT-2003-503330). NR 34 TC 27 Z9 27 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2005 VL 2 IS 5 BP 233 EP 241 DI 10.1159/000090362 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V24IM UT WOS:000208404100001 PM 16909003 ER PT J AU Osei-Hyiaman, D Depetrillo, M Harvey-White, J Bannon, AW Cravatt, BF Kuhar, MJ Mackie, K Palkovits, M Kunos, G AF Osei-Hyiaman, D Depetrillo, M Harvey-White, J Bannon, AW Cravatt, BF Kuhar, MJ Mackie, K Palkovits, M Kunos, G TI Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide SO NEUROENDOCRINOLOGY LA English DT Article DE food intake behavior; endocannabinoids; cannabinoid receptors; fatty acid amide hydrolase; cocaine- and amphetamine-related transcript peptide; transgenic mice; arcuate nucleus; paraventricular nucleus; periventricular hypothalamic area; amygdala; bed nucleus of the Stria terminalis; immunocytochemistry ID CANNABINOID RECEPTOR ANTAGONIST; CORTICOTROPIN-RELEASING-FACTOR; ACID AMIDE HYDROLASE; INDUCED OBESE MICE; FOOD-INTAKE; REGULATED TRANSCRIPT; CART PEPTIDES; BODY-WEIGHT; HYPOTHALAMIC CART; GENE-EXPRESSION AB Endocannabinoids acting at CB1 cannabinoid receptors ( CB1) increase appetite. In view of the predominant presynaptic localization of CB1 in the brain, we tested the hypothesis that the orexigenic effect of endocannabinoids involves inhibition of the release of a tonically active anorexigenic mediator, such as the peptide product of the cocaine- and amphetamine-related transcript ( CART). The CB1 antagonist rimonabant inhibited food intake in food-restricted wild-type mice, but not in their CART-deficient littermates. Mice deficient in fatty acid amide hydrolase ( FAAH), the enzyme responsible for the in vivo metabolism of the endocannabinoid anandamide, have reduced levels of CART-immunoreactive nerve fibers and terminals in several brain regions implicated in appetite control, including the arcuate, dorsomedial and periventricular nuclei of the hypothalamus, the amygdala, the bed nucleus of the stria terminalis and the nucleus accumbens, and treatment of FAAH(-/-) mice with rimonabant, 3 mg/kg/day for 7 days, increased CART levels toward those seen in FAAH(+/+) wild-type controls. In contrast, no difference in the density of CART-immunoreactive fibers was observed in the median eminence and the paraventricular nucleus of FAAH(+/+) and FAAH(-/-) mice. Acute treatment of wild-type mice with the cannabinoid agonist HU-210 resulted in elevated CART levels in the dorsomedial nucleus and the shell portion of the nucleus accumbens. These observations are compatible with CART being a downstream mediator of the CB1-mediated orexigenic effect of endogenous anandamide. Copyright (c) 2005 S. Karger AG, Basel. C1 NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Amgen Inc, Neurosci, Thousand Oaks, CA 91320 USA. Scripps Inst, La Jolla, CA USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Neurosci, Atlanta, GA 30322 USA. Univ Washington, Dept Physiol, Seattle, WA 98195 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. RP Kunos, G (reprint author), NIAAA, Sect Neuroendocrinol, NIH, 5625 Fishers Lane Rm 2S-24,MSC 9413, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI Mackie, Kenneth/B-7358-2011; Mackie, Ken/E-3715-2013; Palkovits, Miklos/F-2707-2013; OI Mackie, Ken/0000-0001-8501-6199; Palkovits, Miklos/0000-0003-0578-0387 FU NCRR NIH HHS [RR00165]; NIDA NIH HHS [DA00286, DA00418, DA015197, DA017259, DA10732, DA11322] NR 49 TC 81 Z9 82 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2005 VL 81 IS 4 BP 273 EP 282 DI 10.1159/000087925 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 967HG UT WOS:000232081700007 PM 16131814 ER PT J AU Radziszewska, B Hart, RG Wolf, PA D'Agostino, RB Cutler, JA AF Radziszewska, B Hart, RG Wolf, PA D'Agostino, RB Cutler, JA TI Clinical research in primary stroke prevention: Needs, opportunities, and challenges SO NEUROEPIDEMIOLOGY LA English DT Review DE stroke prevention; clinical trial; risk factors; primary prevention ID CORONARY-HEART-DISEASE; INTIMA-MEDIA THICKNESS; MAJOR RISK-FACTORS; CAROTID-ARTERY STENOSIS; ISOLATED SYSTOLIC HYPERTENSION; NUTRITION EXAMINATION SURVEY; SILENT BRAIN INFARCTS; SURROGATE END-POINTS; 3RD NATIONAL-HEALTH; C-REACTIVE PROTEIN AB Most ( similar to 70%) of strokes are first-ever strokes, and hence to substantially reduce the neurological burden, primary prevention is crucial. Here, highlights of the National Institute of Neurological Disorders and Stroke workshop 'Stroke Risk Assessment and Future Stroke Primary Prevention Trials' held January 12 - 13, 2004 are summarized. The Workshop discussions focused on stroke risk assessment; the high-risk vs. population-based approaches to primary prevention; desirable characteristics of candidate treatments and potential novel treatments, such as the 'polypill'; subclinical disease as risk assessment tool and as surrogate outcome, and methodological issues in stroke primary prevention trials. The importance of assessing cognitive decline as an important consequence of covert and overt vascular injury of the brain was emphasized. The scientific or logistic barriers to stroke primary prevention trials are challenging, but are not insurmountable. Copyright (C) 2005 S. Karger AG, Basel. C1 NINDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Radziszewska, B (reprint author), NINDS, Ctr Neurosci, NIH, 6001 Execut Blvd,MSC 9520, Bethesda, MD 20892 USA. EM br94h@nih.gov NR 108 TC 9 Z9 9 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2005 VL 25 IS 2 BP 91 EP 104 DI 10.1159/000086342 PG 14 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 947RC UT WOS:000230662900007 PM 15956806 ER PT J AU Howard, VJ Cushman, M Pulley, L Gomez, CR Go, RC Prineas, RJ Graham, A Moy, CS Howard, G AF Howard, VJ Cushman, M Pulley, L Gomez, CR Go, RC Prineas, RJ Graham, A Moy, CS Howard, G TI The reasons for geographic and racial differences in stroke study: Objectives and design SO NEUROEPIDEMIOLOGY LA English DT Article DE cerebrovascular disorders, epidemiology; cohort studies; epidemiologic methods; African-Americans; risk factors; geography; Southeastern United States; prospective studies ID UNITED-STATES; ISCHEMIC-STROKE; MORTALITY; BLACKS; HEALTH; QUESTIONNAIRE; POPULATION; BELT; ATHEROSCLEROSIS; CLASSIFICATION AB The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study is a national, population-based, longitudinal study of 30,000 African-American and white adults aged >= 45 years. The objective is to determine the causes for the excess stroke mortality in the Southeastern US and among African-Americans. Participants are randomly sampled with recruitment by mail then telephone, where data on stroke risk factors, sociodemographic, lifestyle, and psychosocial characteristics are collected. Written informed consent, physical and physiological measures, and fasting samples are collected during a subsequent in-home visit. Participants are followed via telephone at 6-month intervals for identification of stroke events. The novel aspects of the REGARDS study allow for the creation of a national cohort to address geographic and ethnic differences in stroke. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. NINDS, Rockville, MD USA. Examinat Management Serv Inc, Dallas, TX USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Alabama Neurol Inst, Birmingham, AL USA. Univ Arkansas Hlth Sci Univ, Dept Hlth Behav, Little Rock, AR USA. Univ Vermont, Dept Med, Lab Clin Biochem Res, Burlington, VT USA. Univ Vermont, Dept Pathol, Lab Clin Biochem Res, Burlington, VT USA. RP Howard, VJ (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol, 1665 Univ Blvd,Room 210F,Ryals Bldg, Birmingham, AL 35294 USA. EM vjhoward@uab.edu FU NINDS NIH HHS [R01 NS041588, U01 NS041588] NR 42 TC 382 Z9 383 U1 5 U2 16 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2005 VL 25 IS 3 BP 135 EP 143 DI 10.1159/000086678 PG 9 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 961ZG UT WOS:000231700200005 PM 15990444 ER PT J AU Freedman, DM Travis, LB Gridley, G Kuncl, RW AF Freedman, DM Travis, LB Gridley, G Kuncl, RW TI Amyotrophic lateral sclerosis mortality in 1.9 million US cancer survivors SO NEUROEPIDEMIOLOGY LA English DT Article DE amyotrophic lateral sclerosis; Parkinson's disease; cancer; melanoma; lymphoproliferative; registry; smoking; tobacco ID MOTOR-NEURON DISEASE; PARKINSONS-DISEASE; CIGARETTE-SMOKING; DEATH CERTIFICATES; ACCURACY; EPIDEMIOLOGY; EXPRESSION; ETIOLOGY; MELANOMA; CLUES AB Background: Large cancer registries offer the opportunity to explore and generate hypotheses about the pathogenesis of cancer and other diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Methods: Using data from nine population-based cancer registries of the Surveillance, Epidemiology, and End Results ( SEER) Program of the US National Cancer Institute (NCI) and death certificates, we followed 1.9 million cancer survivors who were diagnosed between 1973 and 2000 and who survived at least 1 year, through the year 2000. The outcome of interest was the standardized mortality ratio (SMR) of observed to expected ALS deaths among cancer survivors. To assess the validity of the study design, we also examined associations with Parkinson's disease mortality, which we expected to be inversely associated with smoking-related cancers. Results: There was no significantly increased risk or deficit of ALS mortality for all cancer sites combined ( SMR = 1.0). Parkinson's disease mortality was, as expected, significantly and inversely associated with smoking-related cancers. Both ALS and Parkinson's disease mortality were significantly elevated following melanoma (SMR = 1.6; 95% CI = 1.1 - 2.2; SMR = 1.5; 1.2 - 1.8, respectively). Contrary to previous hypotheses, ALS was unrelated to lymphomas or lymphoproliferative malignancies and was not associated with smoking-related cancers. Conclusions: In this exploratory study, we observed a modest, significant association between melanoma and both ALS and Parkinson's disease mortality. It would be useful to explore these findings in other large national databases that are able to link cancer and ALS and Parkinson's disease. Copyright (C) 2005 S. Karger AG, Basel. C1 NCI, Div Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Bryn Mawr Coll, Dept Biol, Bryn Mawr, PA 19010 USA. RP Freedman, DM (reprint author), NCI, Div Epidemiol & Genet, NIH, DHHS, EPS Room 7036,6120 Exec Blvd, Bethesda, MD 20892 USA. EM mf101e@nih.gov NR 25 TC 24 Z9 24 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2005 VL 25 IS 4 BP 176 EP 180 DI 10.1159/000087447 PG 5 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 978ME UT WOS:000232876700002 PM 16103728 ER PT J AU Rosano, C Simonsick, EM Harris, TB Kritchevsky, SB Brach, J Visser, M Yaffe, K Newman, AB AF Rosano, C Simonsick, EM Harris, TB Kritchevsky, SB Brach, J Visser, M Yaffe, K Newman, AB CA Hlth ABC Collaborative Res Grp TI Association between physical and cognitive function in healthy elderly: The health, aging and body composition study SO NEUROEPIDEMIOLOGY LA English DT Article DE physical function; cognitive performance; gait speed; well-functioning elderly ID STROKE REHABILITATION; EXTRAPYRAMIDAL SIGNS; SENILE DEMENTIA; ALZHEIMER-TYPE; OLDER ADULTS; PERFORMANCE; IMPAIRMENT; WOMEN; MOTOR; DECLINE AB Performance measures of physical function ( gait speed, chair stands, standing balance) and cognitive function [Teng-modified Mini-Mental Status Exam (3MS) and digit symbol substitution test (DSST)] were assessed at baseline in 3,075 participants in the Health, Aging and Body Composition Study. Each physical function measure was examined for the strength and magnitude of association with cognitive function. All physical function measures were associated with both the 3MS and DSST scores (p < 0.001), and in multivariate analysis each relationship was independent of demographic characteristics, weight, physical activity and comorbid health conditions of participants. The association of motor performance was consistently greater for the DSST than the 3MS and, among the motor tests, gait speed retained a significant association with both cognitive measures independent of demographic, weight, physical activity and comorbid health conditions. In this large cohort of high-functioning older adults, the correlation between physical and cognitive function was not entirely explained by demographics. Longitudinal studies are needed to determine the direction of causality in this relationship. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. NIA, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. RP Rosano, C (reprint author), Univ Pittsburgh, Dept Med, Div Geriatr Med, 930 Scaife Hall, Pittsburgh, PA 15260 USA. EM RosanoC@edc.pitt.edu RI Brach, Jennifer/A-6912-2009; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 NR 31 TC 116 Z9 118 U1 0 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2005 VL 24 IS 1-2 BP 8 EP 14 DI 10.1159/000081043 PG 7 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 883OC UT WOS:000226021500002 PM 15459503 ER PT J AU Coffman, CJ Horner, RD Grambow, SC Lindquist, J AF Coffman, CJ Horner, RD Grambow, SC Lindquist, J CA Investigators VA cooperative Studi TI Estimating the occurrence of amyotrophic lateral sclerosis among Gulf War (1990-1991) Veterans using capture-recapture methods - An assessment of case ascertainment bias SO NEUROEPIDEMIOLOGY LA English DT Article DE ascertainment; amyotrophic lateral sclerosis; capture-recapture; Gulf War; log-linear models; sample coverage ID EPIDEMIOLOGY; MODELS AB Objective: Using data from a recent report that indicated a 2-fold higher risk of amyotrophic lateral sclerosis (ALS) among veterans of the 1991 Gulf War, we applied capture-recapture methodology to estimate possible under-ascertainment of ALS cases among deployed and non-deployed military personnel who were on active duty during that war. Study Design and Setting: One of the most serious concerns facing field epidemiological investigations is that of case ascertainment bias, particularly when it is differential among the study groups. Capture-recapture methods, however, have promise as an approach to assessing the impact of case ascertainment bias in such studies. To overcome potential limitations of any one approach, three different estimation methods were used: log-linear models, sample coverage, and ecological models, to obtain a comprehensive view of under-ascertainment bias in these populations. Results: All three approaches indicated differential undercount of ALS cases with modest under-ascertainment likely to have occurred among non-deployed military personnel, but little under-ascertainment among the deployed. After correcting the rates for under-ascertainment, the age-adjusted risk of ALS remained elevated among military personnel who had been deployed to S.W. Asia during the 1991 Gulf War, confirming the earlier report. Conclusions:Capture-recapture methods area useful approach to assessing the magnitude of case ascertainment bias in epidemiological studies from which ascertainment-adjusted estimates of rates and relative risks can be calculated. Copyright (C) 2005 S. Karger AG, Basel. C1 Durham VA Med Ctr, Inst Clin & Epidemiol Res, Biostat Unit, Durham, NC USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. NINDS, Off Minor Hlth & Res, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Coffman, CJ (reprint author), VA Med Ctr, HSR&D 152,508 Fulton St,Bldg 16,Room 70, Durham, NC 27705 USA. EM Cynthia.Coffman@duke.edu RI Grambow, Steven/E-1422-2015 OI Grambow, Steven/0000-0001-6037-3253 NR 18 TC 38 Z9 38 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2005 VL 24 IS 3 BP 141 EP 150 DI 10.1159/000083297 PG 10 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 915JI UT WOS:000228300100005 PM 15650320 ER PT S AU Horwitz, B Glabus, MF AF Horwitz, B Glabus, MF BE Glabus, MF TI Neural modeling and functional brain imaging: The interplay between the data-fitting and simulation approaches SO NEUROIMAGING, PT A SE International Review of Neurobiology LA English DT Review ID WORKING-MEMORY; EFFECTIVE CONNECTIVITY; STRUCTURAL EQUATION; PREFRONTAL CORTEX; FMRI; NETWORK; PET; COGNITION; SYSTEM; SCHIZOPHRENIA AB This paper discusses the use of computational neural modeling with functional neuroimaging data, especially the data obtained from positron emission tomography and functional magnetic resonance imaging (fMRI) studies of human cognition. We point out that such data require network analysis to most thoroughly interpret them. Two types of modeling methods are discussed. The first is systems-level modeling, which attempts to determine the nodes of the neural networks mediating specific tasks and die strengths of the interactions between the nodes. The second is large-scale neural modeling, which uses large numbers of neurally realistic elements, arranged into different interacting populations and regions, to simulate the tasks of interest, the neural activities in the multiple populations, and the neuroimaging data (e.g., fMRI) in each region of the model for comparison with experimental data. We will lastly show that these two types of modeling can be combined and used to obtain insight into interregional neural interactions. C1 Natl Inst Deafness & Other Commun Disorders, Sect Brain Imaging & Modeling, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Dept Psychiat, Lab Biol Psychiat, Shreveport, LA 71130 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Brain Imaging & Modeling, NIH, Bethesda, MD 20892 USA. NR 55 TC 5 Z9 5 U1 4 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-366867-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2005 VL 66 BP 267 EP + DI 10.1016/S0074-7742(05)66009-6 PG 26 WC Neurosciences SC Neurosciences & Neurology GA BDL31 UT WOS:000234110000009 PM 16387207 ER PT J AU Tost, H Ende, G Ruf, M Henn, FA Meyer-Lindenberg, A AF Tost, H Ende, G Ruf, M Henn, FA Meyer-Lindenberg, A TI Functional imaging research in schizophrenia SO NEUROIMAGING, PT B SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; WORKING-MEMORY PERFORMANCE; ANTERIOR CINGULATE CORTEX; VAL(108/158) MET GENOTYPE; FRONTAL-LOBE DYSFUNCTIONS; O-METHYLTRANSFERASE COMT; STROOP TASK-PERFORMANCE; EVENT-RELATED FMRI; CARD SORTING TEST; AUDITORY HALLUCINATIONS AB In the preceding decade, functional neuroimaging has emerged as a pivotal tool for psychiatric research. Techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) help bridge the gap between genetic and molecular mechanisms and psychological and behavioral phenomena by characterizing brain dysfunction underlying psychiatric disorders on the neural systems level. This has been of particular relevance for schizophrenia research. This chapter reviews important fMRI studies in neurocognitive domains relevant for schizophrenia, such as motor, visual, auditory, attentional, and working memory function, as well as advances in the visualization of medication effects and the functional characterization of susceptibility genes. C1 Univ Heidelberg, Fac Clin Med Mannheim, NMR Res Psychiat, Cent Inst Mental Hlth, D-68072 Mannheim, Germany. NIH, Neuroimaging Core Facil & Unit, Bethesda, MD 20892 USA. NIH, Intergrat Neuroimaging Genes Cognit & Psychosis P, Bethesda, MD 20892 USA. RP Tost, H (reprint author), Univ Heidelberg, Fac Clin Med Mannheim, NMR Res Psychiat, Cent Inst Mental Hlth, D-68072 Mannheim, Germany. RI Ende, Gabriele/B-7012-2009; OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 119 TC 11 Z9 12 U1 5 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2005 VL 67 BP 95 EP + DI 10.1016/S0074-7742(05)67004-3 PG 26 WC Neurosciences SC Neurosciences & Neurology GA BDL32 UT WOS:000234110200004 PM 16291021 ER PT J AU Thompson, PM Sowell, ER Gogtay, N Giedd, JN Vidal, CN Hayashi, KM Leow, A Nicolson, R Rapoport, JL Toga, AW AF Thompson, PM Sowell, ER Gogtay, N Giedd, JN Vidal, CN Hayashi, KM Leow, A Nicolson, R Rapoport, JL Toga, AW TI Structural MRI and brain development SO NEUROIMAGING, PT B SE INTERNATIONAL REVIEW OF NEUROBIOLOGY LA English DT Review ID CHILDHOOD-ONSET SCHIZOPHRENIA; CORTICAL GRAY-MATTER; DEFORMATION-BASED MORPHOMETRY; NUCLEAR MAGNETIC-RESONANCE; 1ST EPISODE SCHIZOPHRENIA; PRENATAL ALCOHOL EXPOSURE; IN-VIVO; ALZHEIMERS-DISEASE; CALLOSAL MORPHOLOGY; GENETIC INFLUENCES AB Magnetic resonance imaging (MRI) scans provide exceptionally detailed information on how the human brain changes throughout childhood, adolescence, and into old age. We describe several approaches for understanding developmental changes in brain structures based on MRI. Adas-based "parcellation" methods, for example, measure volumes of brain substructures, revealing how they change with age. Growth curves for different brain structures can be compiled, describing the expected trajectories of normal development. Additional computational anatomy techniques can be used to map spatial patterns of brain growth and tissue loss in individual children. Changes in cortical features, such as gray matter thickness, asymmetry, and complexity, can also be mapped. Individual maps can then be combined across subjects to make statistical maps or dynamic "time-lapse movies" that reveal systematic features of brain development in population subgroups while retaining information on their variance. We review several large-scale studies of brain development, including longitudinal studies in which children were scanned repeatedly with structural MRI at 2-year intervals for periods of up to 10 years. Image processing algorithms were then applied to recover detailed information from the resulting image databases. We describe the approaches necessary to compare brain MRI data across groups differing in age, covaried with gender, developmental disorders, or genotype. These methods reveal unsuspected links between development and cognition and can help discover genetic and environmental factors that affect development. These brain maps also chart the anatomical sequence of healthy brain maturation and visualize how it is derailed in neuropsychiatric disorders such as schizophrenia, autism, fetal alcohol syndrome, and Williams syndrome. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Brain Mapping Div,Lab Neuro Imaging, Los Angeles, CA 90095 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Psychiat & Biomed Phys, London, ON N6A 5B8, Canada. RP Thompson, PM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Brain Mapping Div,Lab Neuro Imaging, Los Angeles, CA 90095 USA. RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Leow, Alex/K-3236-2014; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Leow, Alex/0000-0002-5660-8651; Giedd, Jay/0000-0003-2002-8978 FU NCRR NIH HHS [P41 RR13642, R21 RR019771, U54 RR021813]; NIA NIH HHS [P50 AG016570]; NIBIB NIH HHS [P01 EB001955, R21 EB01651]; NIDA NIH HHS [R21 DA15878, R01 DA017831]; NIMH NIH HHS [K01 MH01733] NR 103 TC 49 Z9 49 U1 3 U2 20 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 J9 INT REV NEUROBIOL PY 2005 VL 67 BP 285 EP + DI 10.1016/S0074-7742(05)67009-2 PG 51 WC Neurosciences SC Neurosciences & Neurology GA BDL32 UT WOS:000234110200009 PM 16291026 ER PT S AU Winterer, G Hariri, AR Goldman, D Weinberger, DR AF Winterer, G Hariri, AR Goldman, D Weinberger, DR BE Glabus, MF TI Neuroimaging and human genetics SO NEUROIMAGING, PT B SE International Review of Neurobiology LA English DT Review ID CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER GENE; CEREBRAL-BLOOD-FLOW; APOLIPOPROTEIN-E POLYMORPHISM; DORSOLATERAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; MONOZYGOTIC TWINS DISCORDANT; AUDITORY-EVOKED-POTENTIALS; ANXIETY-RELATED TRAITS; E TYPE-4 ALLELE AB The past few years have seen a rapid expansion of the application of neuroimaging tools to the Investigation of the genetics of brain structure and function. In this chapter, we will (1) highlight the most important steps during the historical development of this research field, (2) explain the major purposes of using neuroimaging in genetic research, (3) address methodological issues that are relevant with regard to the application of neuroimaging in genetic research, (4) give an overview of the present state-of-research, and (5) provide several examples of how neuroimaging was successfully applied. C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NIMH, NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Winterer, G (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RI Hariri, Ahmad/D-5761-2011; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 345 TC 15 Z9 15 U1 9 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 0-12-366868-9 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2005 VL 67 BP 325 EP + DI 10.1016/S0074-7742(05)67010-9 PG 66 WC Neurosciences SC Neurosciences & Neurology GA BDL32 UT WOS:000234110200010 PM 16291027 ER PT J AU Alesci, S De Martino, MU Ilias, I Gold, PW Chrousos, GP AF Alesci, S De Martino, MU Ilias, I Gold, PW Chrousos, GP TI Glucocorticoid-induced osteoporosis: From basic mechanisms to clinical aspects SO NEUROIMMUNOMODULATION LA English DT Review DE glucocorticoids; bone; osteoporosis; fracture ID CORTICOSTEROID-INDUCED OSTEOPOROSIS; BONE-MINERAL DENSITY; OSTEOBLAST-LIKE CELLS; GROWTH-FACTOR-BETA; PATIENTS RECEIVING GLUCOCORTICOIDS; INTESTINAL CALCIUM-ABSORPTION; PARATHYROID-HORMONE TREATMENT; HUMAN OSTEOCALCIN PROMOTER; LOW-DOSE CORTICOSTEROIDS; X-RAY ABSORPTIOMETRY AB Glucocorticoid (GC)-induced osteoporosis (GCOP) is the most common cause of osteoporosis in adults aged 20 45 years as well as the most common cause of iatrogenic osteoporosis. GC excess, either endogenous or exogenous, induces bone loss in 30 - 50% of cases. Indeed, bone loss leading to fractures is perhaps the most incapacitating, sometimes partially irreversible, complication of GC therapy. Nevertheless, GCOP is often underdiagnosed and left untreated. The following article provides an update on the cellular and molecular mechanisms implicated in the pathophysiology of GC- induced bone loss, as well as some guidelines on diagnostic, preventive and therapeutic strategies for this medical condition, in an effort to promote a better knowledge and greater awareness of GCOP by both the patient and the physician. Copyright (C) 2005 S. Karger AG, Basel. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Patras, Fac Med, Dept Pharmacol, Patras, Greece. RP Alesci, S (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10 Rm 2D46,10 Ctr Dr MSC-1284, Bethesda, MD 20892 USA. EM alescisa@mail.nih.gov NR 258 TC 29 Z9 30 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2005 VL 12 IS 1 BP 1 EP 19 DI 10.1159/000082360 PG 19 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 904IU UT WOS:000227490100001 PM 15756049 ER PT J AU Vgontzas, AN Bixler, EO Lin, HM Prolo, P Trakada, G Chrousos, GP AF Vgontzas, AN Bixler, EO Lin, HM Prolo, P Trakada, G Chrousos, GP TI IL-6 and its circadian secretion in humans SO NEUROIMMUNOMODULATION LA English DT Article DE interleukin-6; sleep; sleepiness; sleep deprivation; circadian rhythm ID PITUITARY-ADRENAL AXIS; NECROSIS-FACTOR-ALPHA; DAYTIME SLEEPINESS; PLASMA-LEVELS; HEALTHY-MEN; INTERLEUKIN-6 SECRETION; CHRONIC INSOMNIA; BONE-MARROW; IN-VIVO; CYTOKINES AB Interleukin-6 (IL-6) is a pleiotropic cytokine produced by numerous types of immune and nonimmune cells and is involved in many pathophysiologic mechanisms in humans. Many studies suggest that IL-6 is a putative 'sleep factor' and its circadian secretion correlates with sleep/ sleepiness. IL-6 is elevated in disorders of excessive daytime sleepiness such as narcolepsy and obstructive sleep apnea. It correlates positively with body mass index and may be a mediator of sleepiness in obesity. Also the secretion of this cytokine is stimulated by total acute or partial short-term sleep loss reflecting the increased sleepiness experienced by sleep-deprived individuals. Studies that evaluated the 24-hour secretory pattern of IL-6 in healthy young adults suggest that IL-6 is secreted in a biphasic circadian pattern with two nadirs at about 08.00 and 21.00, and two zeniths at about 19.00 and 05.00 h. In contrast, following sleep deprivation or in disorders of sleep disturbance, e. g., insomnia, IL-6 peaks during the day and, based on the level of stress system activity, i.e., cortisol secretion, contributes to either sleepiness and deep sleep ( low cortisol) or feelings of tiredness and fatigue and poor sleep ( high cortisol). In order to address concerns about the potential impact of differences of IL-6 levels between the beginning and the end of the 24-hour blood-drawing experiment, we proceeded with a cosinor analysis of 'detrended' data in young and old healthy individuals. This new analysis did not affect the biphasic circadian pattern of IL-6 secretion in young adults, while it augmented the flattened circadian pattern in old individuals in whom the difference was greater. Finally, IL-6 appears to be somnogenic in rats and exhibits a diurnal rhythm that follows the sleep/wake cycle in these animals. We conclude that IL-6 is a mediator of sleepiness and its circadian pattern reflects the homeostatic drive for sleep. Copyright (C) 2005 S. Karger AG, Basel. C1 Penn State Coll Med, Sleep Res & Treatment Ctr, Dept Psychiat, Hershey, PA USA. Penn State Coll Med, Sleep Res & Treatment Ctr, Dept Hlth Evaluat Sci, Hershey, PA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept PSychiat H073, 500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu NR 46 TC 138 Z9 146 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2005 VL 12 IS 3 BP 131 EP 140 DI 10.1159/000084844 PG 10 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 927SR UT WOS:000229221300001 PM 15905620 ER PT J AU Elenkov, IJ Iezzoni, DG Daly, A Harris, AG Chrousos, GP AF Elenkov, IJ Iezzoni, DG Daly, A Harris, AG Chrousos, GP TI Cytokine dysregulation, inflammation and well-being SO NEUROIMMUNOMODULATION LA English DT Review DE autoimmune diseases; cytokines; inflammation; interleukins; stress; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; GENE-RELATED PEPTIDE; MINIMAL PERSISTENT INFLAMMATION; RESPIRATORY-DISTRESS-SYNDROME; BETA-ADRENERGIC AGONISTS; INDUCED IL-12 PRODUCTION; BLOOD MONONUCLEAR-CELLS; FACTOR-ALPHA RELEASE AB Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro-versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases. Copyright (C) 2005 S. Karger AG, Basel. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Rheumatol Allergy & Immunol, Washington, DC 20007 USA. Integrated Therapeut Grp Inc, Kenilworth, NJ USA. Univ Liege, Liege, Belgium. San Raffaele Res Ctr, Rome, Italy. RP Chrousos, GP (reprint author), NICHHD, NIH, Bldg 10,Room 1E-1-3140, Bethesda, MD 20892 USA. EM Chrousog@mail.nih.gov RI Daly, Adrian /E-2178-2011; OI Daly, Adrian /0000-0001-6130-2975; Harris, Alan/0000-0002-6618-2092 NR 145 TC 240 Z9 247 U1 4 U2 50 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2005 VL 12 IS 5 BP 255 EP 269 DI 10.1159/000087104 PG 15 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 964WN UT WOS:000231911800001 PM 16166805 ER PT J AU Beauchamp, MS AF Beauchamp, MS TI Statistical criteria in fMRI studies of multisensory integration SO NEUROINFORMATICS LA Welsh DT Article DE auditory; visual; multisensory; integration; fMRI; superior temporal sulcus ID HUMAN BRAIN; MANIPULATABLE OBJECTS; NEURAL SYSTEMS; CORTEX; HUMANS; PSYCHOPHYSICS; CONVERGENCE; ACTIVATION; MOVEMENTS; SOFTWARE AB Inferences drawn from functional magnetic resonance imaging (fMRI) studies are dependent on the statistical criteria used to define different brain regions as "active" or "inactive" under the experimental manipulation. In fMRI studies of multisensory integration, additional criteria of multisensory integration, additional criteria are used to classify a subset of the active brain regions as "multisensory". Because there is no general agreement in the literature on the optimal criteria for performing this classification, we investigated the effects of seven different multisensory stat-istical criteria on a single test dataset collected as human subjects performed auditory, visual, and auditory-visual object recognition. Activation maps created using the different criteria differed dramatically. The classification of the superior temporal sulcus (STS) was used as a performance measure, because a large body of converging evidence demonstrates that the STS is important for auditory-visual integration. A commonly proposed criterion, "supra-additivity" or "super-additivity", which requires the multisensory response to be larger than the summed unisensory responses, did not classify STS as multisensory. Alternative criteria, such as requiring the multisensory response to be larger than the maximum or the mean of the unisensory responses, successfully classified STS as multisensory. This practical demonstration strengthens theoretical arguments that the super-additivity is not an appropriate criterion for all studies of multisensory integration. Moreover, the importance of examining evoked fMRI responses, whole brain activation maps, maps from multiple individual subjects, and mixed-effect group maps are discussed in the context of selecting statistical criteria. C1 Natl Inst Mental Hlth, Intramural Res Program, Dept Hlth & Human Serv, Lab Brain & Cognit,NIH, Bethesda, MD USA. RP Beauchamp, MS (reprint author), Natl Inst Mental Hlth, Intramural Res Program, Dept Hlth & Human Serv, Lab Brain & Cognit,NIH, Bethesda, MD USA. EM Michael.S.Beauchamp@uth.tmc.edu FU Intramural NIH HHS; NINDS NIH HHS [R01 NS065395, R01 NS065395-01A2] NR 37 TC 131 Z9 131 U1 1 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PY 2005 VL 3 IS 2 BP 93 EP 113 DI 10.1385/NI:03:02:93 PG 21 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 942ZY UT WOS:000230322600003 PM 15988040 ER PT J AU Maudsley, S AF Maudsley, S TI Special Issue: G proteins and GPCRs in synaptic function and pathology - Introduction SO NEUROMOLECULAR MEDICINE LA English DT Editorial Material C1 NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2005 VL 7 IS 1-2 BP 1 EP 1 DI 10.1385/NMM:7:1:1 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 962CB UT WOS:000231707500001 ER PT J AU Martin, B de Maturana, RL Brenneman, R Walent, T Mattson, MP Maudsley, S AF Martin, B de Maturana, RL Brenneman, R Walent, T Mattson, MP Maudsley, S TI Class II G protein-coupled receptors and their ligands in neuronal function and protection SO NEUROMOLECULAR MEDICINE LA English DT Review DE secretin-like; G protein-coupled receptor (GPCR); neurodegeneration; promiscuity; Alzheimer's disease (AD); Parkinson's disease (PD); neuroprotection; neuropeptide ID GLUCAGON-LIKE PEPTIDE-1; CYCLASE-ACTIVATING POLYPEPTIDE; CORTICOTROPIN-RELEASING-FACTOR; VASOACTIVE-INTESTINAL-PEPTIDE; CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR-I; HORMONE-RELATED PEPTIDE; DEPENDENT NEUROTROPHIC FACTOR; ACTIVITY-MODIFYING PROTEINS; CEREBELLAR GRANULE NEURONS AB G protein-coupled receptors (GPCRs) play pivotal roles in regulating the function and plasticity of neuronal circuits in the nervous system. Among the myriad of GPCRs expressed in neural cells, class IIGPCRs which couples predominantly to the Gs-adenylate cyclase-cAMP signaling pathway, have recently received considerable attention for their involvement in regulating neuronal survival. Neuropeptides that activate class IIGPCRs include secretin, glucagon-like peptides (GLP-1 and GLP-2), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating peptide (PACAP), corticotropin-releasing hormone (CRH), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), and calcitonin-related peptides. Studies of patients and animal and cell culture models, have revealed possible roles for class IIGPCRs signaling in the pathogenesis of several prominent neurodegenerative conditions including stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Many of the peptides that activate class IIGPCRs promote neuron survival by increasing the resistance of the cells to oxidative, metabolic, and excitotoxic injury. A better understanding of the cellular and molecular mechanisms by which class IIGPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders. C1 NIA, Neurosci Lab, Intramural Res Program, Ctr Gerontol Res, Baltimore, MD 21224 USA. ArdanaBiosci Ltd, Edinburgh EH1, Midlothian, Scotland. RP NIA, Neurosci Lab, Intramural Res Program, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM maudsleyst@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000318-01] NR 293 TC 44 Z9 45 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PY 2005 VL 7 IS 1-2 BP 3 EP 36 DI 10.1385/NMM:7:1:3 PG 34 WC Neurosciences SC Neurosciences & Neurology GA 962CB UT WOS:000231707500002 PM 16052036 ER PT J AU Agnati, LF Ferre, S Burioni, R Woods, A Genedani, S Franco, R Fuxe, K AF Agnati, LF Ferre, S Burioni, R Woods, A Genedani, S Franco, R Fuxe, K TI Existence and theoretical aspects of homomeric and heteromeric dopamine receptor complexes and their relevance for neurological diseases SO NEUROMOLECULAR MEDICINE LA English DT Review DE receptor-receptor interactions; dopamine homomers; dopamine heteromers; receptor mosaic; receptor oligomerization; free energy landscape; entropy; enthalpy; basal ganglia ID ADENOSINE A(2A) RECEPTORS; CENTRAL-NERVOUS-SYSTEM; METABOTROPIC GLUTAMATE RECEPTORS; PROTEIN-COUPLED RECEPTORS; GAMMA-AMINOBUTYRIC-ACID; PARKINSONS-DISEASE; A(1) RECEPTORS; D1 RECEPTOR; 6-HYDROXYDOPAMINE-LESIONED RATS; ANTAGONISTIC INTERACTION AB Dopamine (DA) and other receptors physically interact in the plasma membrane of basal ganglia neurons forming receptor mosaics (RMs). Two types of RMs are discussed, homomers formed only by DA-receptor (DA-R) subtypes and heteromers formed by DA-R associated with other receptors, such as A2A, A1, mGluR5, N-methyl-D-aspartate (NMDA), gamma-aminobutryic acid (GABA)-A, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. By being part of horizontal molecular networks, RMs tune multiple effector systems already at membrane level, such as G protein regulated inward rectifying potassium channels and dopamine transporter activity. Also, ligand-gated ion channels such as GABA-A and NMDA receptors are modulated by DA-R, e.g., in the striatal GABA output neurons through the formation of heteromeric complexes with these receptors. Thus, intramembrane DA-R-receptor interactions play an important role in the information handling in the basal ganglia. On this basis, functional implications of DA RM in physiological and pathological conditions are discussed. The effects of temperature on RM are discussed not only because receptor-decoding mechanisms are temperature sensitive, but also in view of the suggestion that possible ordering effects (i.e., changes in the entropy of a receptor complex) induced by a ligand are as a result of alterations in the receptor oligomerization (i.e., are related to rearrangements of the RM). Hence, brain temperature may have profound effects on brain integrative functions not only because its effects on the kinetics of biochemical reactions, but also for its effects on receptor geometry, building up of RM, and alterations in protein expression, as is the case of H-channels following febrile seizures. C1 Univ Modena & Reggio Emilia, Dept Biomed Sci, Via Campi 287, I-41100 Modena, Italy. Natl Inst Drug Abuse, Dept Hlth & Human Serv, Intramural Res Program, Baltimore, MD 21224 USA. Univ Parma, Dept Phys, I-43100 Parma, Italy. Univ Parma, Ist Nazl Fis Nucl, I-43100 Parma, Italy. Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Univ Modena & Reggio Emilia, Dept Biomed Sci, Via Campi 287, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Franco, Rafael/C-3694-2015; Genedani, Susanna/K-4370-2016; Burioni, Roberto /F-2396-2012; Burioni, Raffaella/C-6780-2017; Ferre, Sergi/K-6115-2014 OI Franco, Rafael/0000-0003-2549-4919; Genedani, Susanna/0000-0003-1526-153X; Fuxe, Kjell/0000-0001-8491-4288; Ferre, Sergi/0000-0002-1747-1779 NR 126 TC 19 Z9 19 U1 2 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PY 2005 VL 7 IS 1-2 BP 61 EP 78 DI 10.1385/NMM:7:1:61 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 962CB UT WOS:000231707500005 PM 16052039 ER PT J AU Arumugam, TV Granger, DN Mattson, MP AF Arumugam, TV Granger, DN Mattson, MP TI Stroke and T-cells SO NEUROMOLECULAR MEDICINE LA English DT Review DE leukocyte; adhesion; stroke; T-cells; ischemia/reperfusion injuries; inflammation ID TUMOR-NECROSIS-FACTOR; CEREBRAL-ARTERY OCCLUSION; ISCHEMIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; INTERCELLULAR-ADHESION MOLECULE-1; GROWTH-FACTOR-BETA; SELECTIN GLYCOPROTEIN LIGAND-1; PROTECTS HIPPOCAMPAL-NEURONS; INFLAMMATORY-BOWEL-DISEASE; MESSENGER-RNA EXPRESSION AB The microvasculature of the brain region affected by a stroke assumes an inflammatory phenotype that is characterized by endothelial cell activation and barrier dysfunction and the recruitment of adherent leukocytes. Although most attention has been devoted to the possible role of neutrophils in the tissue responses to ischemic stroke there is evidence that T-lymphocytes also accumulate in the postischemic brain. Although comparable detailed analyses of lymphocyte involvement in ischemic brain injury have not been performed, emerging findings suggest a role for T-cells in the pathogenesis of ischemic stroke. The recruitment of T-cells to the site of brain injury is critically dependent on the coordinated expression of adhesion molecules on the activated capillary endothelium. Whether the recruited lymphocytes are acting directly on brain tissue or indirectly through activation of other circulating blood cells and/or extravascular cells remain unclear. Cytotoxic CD8(+) T-cells may induce brain injury through molecules released from their cytotoxic granules. CD4(+) T-helper 1 (TH1) cells, which secrete proinflammatory cytokines, including interleukin-2 (IL2), IL-12, interferon-gamma, and tumor necrosis factor-alpha, may play a key role in the pathogenesis of stroke, whereas CD4(+) TH2 cells may play a protective role through anti-inflammatory cytokines such as IL-4, IL-5, IL-10, and IL-13. T-cells should be considered as therapeutic targets for ischemic stroke. However, because infection is a leading cause of mortality in the postacute phase of ischemic stroke, and considering anti-inflammatory role of CD4(+)TH2, treatment targeting T-cells should be carefully designed to reduce deleterious and enhance protective actions of T-cells. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. RP Arumugam, TV (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM arumugamt@mail.nih.gov RI Arumugam, Thiruma/C-7969-2009; Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012 NR 99 TC 87 Z9 95 U1 2 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PY 2005 VL 7 IS 3 BP 229 EP 242 DI 10.1385/NMM:7:3:229 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 984JK UT WOS:000233299000006 PM 16247183 ER PT J AU Huang, FL Huang, KP AF Huang, FL Huang, KP TI Role of neurogranin in group 1 mGluR-dependent LTD - A study with neurogranin-knockout mice SO NEUROPHARMACOLOGY LA English DT Meeting Abstract CT 5th International Meeting on Metabotropic Glutamate Receptors CY SEP 18-23, 2005 CL Taormina, ITALY C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2005 VL 49 SU 1 MA 59 BP 249 EP 249 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 964MJ UT WOS:000231884900081 ER PT J AU Reddy, DS O'Malley, BW Rogawski, MA AF Reddy, DS O'Malley, BW Rogawski, MA TI Anxiolytic activity of progesterone in progesterone receptor knockout mice SO NEUROPHARMACOLOGY LA English DT Article DE progesterone; progesterone receptor; allopregnanolone; finasteride; GABA(A) receptor; neurosteroid; anxiety; elevated plus maze ID WILD-TYPE MICE; NEUROACTIVE STEROIDS; PREMENSTRUAL-SYNDROME; GABA(A) RECEPTORS; ANTICONVULSANT ACTIVITY; ESTROUS-CYCLE; RAT-BRAIN; PLUS-MAZE; NEUROSTEROID ALLOPREGNANOLONE; REPRODUCTIVE FUNCTIONS AB Progesterone is an anxiolytic steroid that could play a role in the regulation of anxiety in women. However, the mechanism by which progesterone decreases anxiety is incompletely understood. Progesterone affects the function of the brain by two distinct mechanisms. Progesterone regulates reproductive behavior by activating intracellular progesterone receptors (PRs). In addition, progesterone is believed to influence neuronal activity through its conversion to allopregnanolone, a neurosteroid that acts as a positive allosteric modulator of GABA(A) receptors. The extent to which the anxiolytic action of progesterone requires PRs is uncertain. In this study, we utilized PR knockout (PRKO) mice bearing a targeted null mutation of the PR gene that abrogates the function of both PR-A and PR-B subtypes to determine the requirement for PRs in the anxiolytic actions of progesterone. The absence of PR receptor protein expression in PRKO brain was confirmed by immunocytochemistry. in PRKO mice and their isogenic wild-type (WT) littermates, progesterone administration was associated with a dose-dependent rise in plasma allopregnanolone concentrations and corresponding anxiolytic effects in the elevated plus maze test. PRKO mice exhibited a greater anxiolytic response than WT animals although the allopregnanolone levels were similar in the two genotypes. Allopregnanolone also exhibited anxiolytic effects, but the magnitude of the response was similar in both genotypes. Pretreatment of PRKO mice with finasteride, a 5alpha-reductase inhibitor that blocks the conversion of progesterone to allopregnanolone, completely prevented the anxiolytic activity of progesterone, but had no effect on the response to allopregnanolone, demonstrating that allopregnanolone (or other 5alpha-reduced metabolites of progesterone) accounts for the response to the parent steroid hormone. These results provide direct evidence that the anxiolytic action of progesterone does not require PRs. However, PR activation by progesterone may influence the anxiolytic response since PRKO mice were more sensitive to progesterone. (C) 2004 Elsevier Ltd. All rights reserved. C1 N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27606 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NINDS, Epilepsy Res Stn, NIH, Bethesda, MD 20892 USA. RP Reddy, DS (reprint author), N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM samba_reddy@ncsu.edu RI Rogawski, Michael/B-6353-2009; OI Rogawski, Michael/0000-0002-3296-8193; Reddy, Samba/0000-0003-2735-9550 FU NICHD NIH HHS [HD 07495, HD 07857] NR 74 TC 96 Z9 99 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2005 VL 48 IS 1 BP 14 EP 24 DI 10.1016/j.neuropharm.2004.09.002 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 887RY UT WOS:000226324400002 PM 15617723 ER PT J AU Zapata, A Shippenberg, TS AF Zapata, A Shippenberg, TS TI Lack of functional D2 receptors prevents the effects of the D3-preferring agonist (+)-PD 128907 oil dialysate dopamine levels SO NEUROPHARMACOLOGY LA English DT Article DE knock out mice; microdialysis; autoreceptor; ventral striatum; nucleus accumbens ID D-3 RECEPTOR; IN-VIVO; LOCOMOTOR-ACTIVITY; MUTANT MICE; RAT-BRAIN; RELEASE; D3; TARGET; SCHIZOPHRENIA; LOCALIZATION AB substantial pharmacological evidence is consistent with an inhibitory effect of D3 receptor activation on dopamine (DA) release. Although receptor selectivity of the ligands employed in initial studies has been questioned. studies employing new. more selective. compounds continue to support an involvement of this receptor subtype in regulating extracellular dopamine levels in the dorsal striatum and nucleus accumbens. Consistent with this hypothesis, microdialysis studies have shown that the dose-effect curve for (+)-PD 128907, a moderately selective D3 agonist, is shifted to the right in D3 knock out mice. The present microdialysis studies sought to further examine the role of D2 vs. D3 receptors in mediating (+)-PD 128907-evoked alterations in basal and depolarization-evoked DA levels. Dialysate DA levels were determined in D2 knock out mice and wild type litter-mate controls following both systernic and local administration of (+)-PD 128907. In view of regional differences in D3 receptor localization. studies were conducted in the nucleus accumbens. a D3 receptor rich area, and in the dorsal striatum. a region with low 133 receptor abundance. Systemic or reverse dialysis of (+)-PD 128907 into the nucleus accumbens significantly decreased basal and depolarization-evoked DA levels in wild type mice. A similar effect was observed in the dorsal striatum. Regardless or the route of administration, (+)-PD 128907 was ineffective in modulating DA levels in either brain region of D2 knock out mice. These data contrast with previous results in D3 knock out mice and indicate that the D2 receptor is necessary for the inhibition of presynaptic DA neurotransmission produced by a preferential D3 agonist. Based on the documented physical interaction or D2 and D3 receptors in heterologous expression systems. we put forth a hypothesis that reconciles the seemingly paradoxical results of this and previous microdialysis studies. (C) 2004 Elsevier Ltd. All rights reserved. C1 NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Zapata, A (reprint author), NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dive, Baltimore, MD 21224 USA. EM azapata@intra.nida.nih.gov NR 26 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2005 VL 48 IS 1 BP 43 EP 50 DI 10.1016/j.neuropharm.2004.09.003 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 887RY UT WOS:000226324400005 PM 15617726 ER PT S AU Herning, RI Better, W Tate, K Cadet, JL AF Herning, RI Better, W Tate, K Cadet, JL BE Slikker, W Andrews, RJ Trembly, B TI Neuropsychiatric alterations in MDMA users - Preliminary findings SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE MDMA; ecstasy; marijuana; polysubstance abuse; EEG deficits; cerebral perfusion deficits; transcranial Doppler; medical complications ID CEREBRAL-BLOOD-FLOW; COGNITIVE PERFORMANCE; WORKING-MEMORY; ECSTASY USERS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; EEG; IMPAIRMENT; DEMENTIA; DEFICITS; PROFILE AB The use of marijuana is rampant among 3,4-methylene-dioxymethamphetamine (MDMA) users. The co-occurrence of abuse of these two drugs has made it difficult to assess the specific residual effects of MDMA alone. As a first step toward identifying the effects of long-term MDMA use, we studied 8 MDMA abusers, 8 marijuana/MDMA abusers, 15 marijuana abusers (matched in marijuana use without MDMA use), and 17 control subjects. EEG, cerebral blood velocity by pulsed transcranial Doppler (TCD), and psychological measures were collected. Three-minute resting eyes-closed EEG recordings were obtained from 16 electrodes. The EEG was converted to 6 frequency bands (delta, theta, alpha-1, alpha-2, beta-1, and beta-2) using a fast Fourier transformation. Blood flow velocity was determined using a temporal window for the right and left middle cerebral arteries using TCD. Absolute log delta power in the EEG of MDMA abusers at central electrode sites was significantly higher than that of the MDMA/marijuana, marijuana abusers, and control subjects. There were also increases in alpha-2 EEG power observed only in marijuana abusers. The blood flow measure, diastolic velocity, was increased in MDMA abusers whether they used marijuana or not. Because increases in delta power and perfusion deficits are associated with some chronic disorders, our findings in these ecstasy abusers suggest that MDMA use may be associated with a drug-induced neuropathological state. More research is necessary to test these ideas. C1 NIDA, IRP, Mol Neuropsychiat Branch, Baltimore, MD 21224 USA. RP Herning, RI (reprint author), NIDA, IRP, Mol Neuropsychiat Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rherning@intra.nida.nih.gov NR 35 TC 6 Z9 6 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 20 EP 27 DI 10.1196/annals.1344.003 PG 8 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800003 PM 16179502 ER PT S AU Wu, X Jiang, XY Marini, AM Lipsky, RH AF Wu, X Jiang, XY Marini, AM Lipsky, RH BE Slikker, W Andrews, RJ Trembly, B TI Delineating and understanding cerebellar neuroprotective pathways - Potential implication for protecting the cortex SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE NMDA receptors; cultured neurons; cognition; NF-kappa B; neuroprotection; ERK 1/2 ID METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; RECEPTOR-MEDIATED NEUROPROTECTION; SIGNAL-REGULATED KINASE; CULTURED NEURONS; GLUTAMATE EXCITOTOXICITY; ATAXIA-TELANGIECTASIA; HIPPOCAMPAL-NEURONS; SYNAPTIC PLASTICITY; DEITERS NEURONES AB The cerebellum is a brain region that is resistant to many of the neurodegenerative disorders such as stroke and Alzheimer's disease. In contrast, the neocortex (cerebrum, cerebral cortex) is vulnerable to these disorders. While there may be many reasons for the differences in vulnerability to acute and chronic neurodegenerative disorders, the cerebellum appears to be equipped with the tools necessary to protect itself against these types of insults. Over the last century, evidence has accumulated to suggest that the cerebellum is also involved in memory and higher cognitive function. We have discovered that intrinsic survival pathways exist in cerebellar granule cells that are regulated by low level stimulation of N-methyl-D-aspartate (NMDA) receptors. Activation of NMDA receptors protects vulnerable neurons against glutamate-mediated excitotoxicity acting on NMDA receptors. This report focuses on how modulation of neuronal survival by NMDA receptors through a brain-derived neurotrophic factor (BDNF)-mediated pathway may be incorporated into a network of cerebellar function, particularly in light of recent findings suggesting that the cerebellum plays a vital role in learning, memory, fear conditioning, and cognitive processing. C1 NIAAA, Unit Mol Genet, Lab Neurogenet, NIH,Sect Mol Genet, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. RP Lipsky, RH (reprint author), NIAAA, Unit Mol Genet, Lab Neurogenet, NIH,Sect Mol Genet, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM rlipsky@mail.nih.gov OI Lipsky, Robert/0000-0001-7753-1473 FU NIAAA NIH HHS [Z01-AA00325] NR 53 TC 10 Z9 12 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 39 EP 47 DI 10.1196/annals.1344.004 PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800007 PM 16179507 ER PT S AU Qin, LY Liu, YX Qian, X Hong, JS Block, ML AF Qin, LY Liu, YX Qian, X Hong, JS Block, ML BE Slikker, W Andrews, RJ Trembly, B TI Microglial NADPH oxidase mediates leurine enkephalin dopaminergic neuroprotection SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE microglial NADPH oxidase; leucine enkephalin (LE); des-tyrosme leucine enkephalin (DTLE); lipopolysaccharide (LPS); tumor necrosis factor-alpha (TNF alpha); neuroprotection; neurotoxicity ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; CORTICAL NEURON/GLIA CULTURES; FEMTOMOLAR CONCENTRATIONS; PARKINSONS-DISEASE; INFLAMMATORY DAMAGE; NEUROTROPHIC FACTOR; TETRAZOLIUM SALT; ACTIVATION; DEGENERATION; INHIBITION AB Here, we report that leucine enkephalin (LE) is neuroprotective to dopaminergic (DA) neurons at femtomolar concentrations through anti-inflammatory properties. Mesencephalic neuron-glia cultures pretreated with femtomolar concentrations of LE (10(-15)-10(-13) M) protected DA neurons from lipopolysaccharide (LPS)-induced DA neurotoxicity, as determined by DA uptake assay and tyrosine hydroxylase (TH) immunocytochemistry (ICC). However, des-tyrosine leucine enkephalin (DTLE), an LE analogue that is missing the tyrosine residue required for binding to the kappa opioid receptor, was also neuroprotective (10(-15)-10(-13) M), as determined by DA uptake assay and TH ICC. Both LE and DTLE (10(-15)-10(-13) M) reduced LPS-induced superoxide production from microglia-enriched cultures. Further, both LE and DTLE (10(-14),10(-13) M) reduced the LPS-induced tumor necrosis factor- alpha (TNF alpha) mRNA and TNF alpha protein from PHOX+/+ microglia, as determined by quantitative real-time RT-PCR and ELISA analysis in mesencephalic neuron-glia cultures, respectively. However, both peptides failed to inhibit TNF alpha expression in PHOX-/- cultures, which are unable to produce extracellular superoxide in response to LPS. Additionally, LE and DTLE (10(-14),10(-13) M) failed to show any neuroprotection against LPS in PHOX-/- cultures. Together, these data indicate that LE and DTLE are neuroprotective at femtomolar concentrations through the inhibition of oxidative insult associated with microglial NADPH oxidase and the attenuation of the ROS-mediated amplification of TNF alpha gene expression in microglia. C1 NIEHS, NIH, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Dalian Univ Technol, Dept Biosci & Biotechnol, Dalian 116024, Peoples R China. NIEHS, Inositol Phosphate Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Block, ML (reprint author), NIEHS, NIH, Neuropharmacol Sect, Lab Pharmacol & Chem, POB 12233,MD F1-01, Res Triangle Pk, NC 27709 USA. EM block@niehs.nih.gov NR 45 TC 25 Z9 25 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 107 EP 120 DI 10.1196/annals.1344.009 PG 14 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800013 PM 16179514 ER PT S AU Hong, JS AF Hong, JS BE Slikker, W Andrews, RJ Trembly, B TI Role of inflammation in the pathogenesisof Parkinson's disease - Models, mechanisms, and therapeutic interventions SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE Parkinson's disease (PD); inflammation; neurodegeneration; microglia; therapy C1 NIEHS, NIH, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Hong, JS (reprint author), NIEHS, NIH, Neuropharmacol Sect, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov NR 0 TC 7 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 151 EP 152 DI 10.1196/annals.1344.054 PG 2 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800017 PM 16179518 ER PT S AU Chuang, DM AF Chuang, DM BE Slikker, W Andrews, RJ Trembly, B TI The antiapoptotic actions of mood stabilizers - Molecular mechanisms and therapeutic potentials SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE BDNF; Bcl-2; excitotoxicity; heat-shock protein; lithium; neurodegeneration; neurogenesis; neuroprotection; valproate ID CEREBRAL CORTICAL-NEURONS; TERM LITHIUM TREATMENT; GLYCOGEN-SYNTHASE KINASE-3-BETA; HISTONE DEACETYLASE INHIBITION; CEREBELLAR GRANULE CELLS; CULTURED BRAIN NEURONS; VALPROIC ACID; GLUTAMATE EXCITOTOXICITY; HUNTINGTONS-DISEASE; NERVOUS-SYSTEM AB Two primary drugs used to treat bipolar mood disorder are lithium and valproate. Emerging evidence supports the notion that both mood stabilizers have neuroprotective effects. In primary cultures of rat cerebellar granule cells and cortical neurons, lithium and valproate robustly and potently protect against glutamate-induced, N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity. The neuroprotective mechanisms involve inactivation of NMDA receptors through inhibition of NR2B tyrosine phosphorylation, activation of cell survival factors such as the PI3-kinase/Akt signaling pathway, and induction of neurotrophic/neuroprotective proteins, including brain-derived neurotrophic factor, heat-shock protein (HSP), and Bcl-2. Both drugs are also effective against other forms of insults such as ER stress in neurally related cell types. The molecular targets likely involve glycogen synthase kinase-3 (GSK-3) and histone deacetylase (HDAC) for lithium and valproate, respectively. in a rat cerebral artery occlusion model of stroke, postinsult treatment with lithium or valproate reduces ischemia-induced brain infarction, caspase-3 activation, and neurological deficits, and these neuroprotective effects are associated. with HSP70 upregulation and, in the case of valproate, HDAC inhibition. In a rat excitotoxic model of Huntington's disease in which an excitotoxin is infused into the striatum to activate NMDA receptors, short-term lithium pretreatment is sufficient to protect against DNA damage, caspase activation, and apoptosis of striatal neurons, and this neuroprotection is concurrent with Bcl-2 induction. Moreover, lithium treatment increases cell proliferation near the site of striatal injury, and some newborn cells have phenotypes of neurons and astroglia. Thus, lithium and valproate are potential drugs for treating some forms of neurodegenerative diseases. C1 NIMH, NIH, Mol Neurobiol Sect, Biol Psychiat Branch,Mood & Anxiety Disorders Pro, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, NIH, Mol Neurobiol Sect, Biol Psychiat Branch,Mood & Anxiety Disorders Pro, Bldg 10,Room 4C-206,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov NR 51 TC 143 Z9 145 U1 0 U2 12 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 195 EP 204 DI 10.1196/annals.1344.018 PG 10 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800022 PM 16179524 ER PT S AU Slikker, W Young, JF Corley, RA Dorman, DC Conolly, RB Knudsen, TB Erstad, BL Luecke, RH Faustman, EM Timchalk, C Mattison, DR AF Slikker, W Young, JF Corley, RA Dorman, DC Conolly, RB Knudsen, TB Erstad, BL Luecke, RH Faustman, EM Timchalk, C Mattison, DR BE Slikker, W Andrews, RJ Trembly, B TI Improving predictive modeling in pediatric drug development: Pharmacokinetics, pharmacodynamics, and mechanistic modeling SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE PBPK; pharmacokinetics; pharmacodynamics; pediatrics; children; modeling ID EXPOSURE-DISEASE CONTINUUM; PROTOTYPE OCULAR TERATOGEN; HEALTH RISK ASSESSMENT; METABOLIZING-ENZYMES; MANGANESE DEPOSITION; HAZARDOUS SUBSTANCES; COMPUTATIONAL MODEL; BASAL GANGLIA; RAT; CHILDREN AB A workshop was conducted on November 18-19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. The goals of the meeting included a description of when, during development, infants/children become adultlike in handling drugs. The issue of incorporating the most recent advances into the predictive models was also addressed: both the use of imaging approaches and genomic information were considered. Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human. C1 US FDA, Natl Ctr Toxicol Res, Res Off, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Pacific NW Natl Lab, Ctr Biol Monitoring & Modeling, Richman, WA USA. CIIT, Ctr Hlth Res, Res Triangle Pk, NC USA. Univ Louisville, Birth Defects Ctr, Syst Anal Lab, Louisville, KY USA. Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. Univ Missouri, Dept Chem Engn, Columbia, MO USA. Univ Washington, Inst Risk Analysis & Risk Commun, Seattle, WA 98195 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Res Off, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov; wslikker@nctr.fda.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; Faustman, Elaine/0000-0002-3085-6403 NR 58 TC 6 Z9 7 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 505 EP 518 DI 10.1196/annals.1344.044 PG 14 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800051 PM 16179559 ER PT J AU Goutagny, R Comte, JC Salvert, D Gomeza, J Yamada, M Wess, J Luppi, PH Fort, P AF Goutagny, R Comte, JC Salvert, D Gomeza, J Yamada, M Wess, J Luppi, PH Fort, P TI Paradoxical sleep in mice lacking M-3 and M-2/M-4 muscarinic receptors SO NEUROPSYCHOBIOLOGY LA English DT Article DE paradoxical sleep; waking; cholinergic; brainstem; EEG; theta rhythm ID PONTINE RETICULAR-FORMATION; EYE-MOVEMENT SLEEP; KNOCK-OUT MICE; ACETYLCHOLINE-RECEPTOR; REM-SLEEP; GENERATION; MICROINJECTION; CARBACHOL; MOUSE; RAT AB Acetylcholine is crucial for the regulation of paradoxical sleep (PS) and EEG theta activity. To determine the contribution of individual muscarinic receptors to these events, we analyzed the sleep-waking cycle and EEG activities of mice lacking functional M-3 or M-2/M-4 receptors. Daily PS amounts were significantly decreased in M3-/-(-22%) but not in M2/M4-/- mice. Further, the theta peak frequency for PS was significantly increased in both M2/M4-/- and M3-/- mice. This study supports the potential role of M-3 rather than M-2 and M-4 muscarinic receptors in the modulation of PS in mice and strengthens the idea that multiple muscarinic receptors contribute to the regulation of the EEG theta activity during PS. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Lyon 1, Inst Federat Neurosci Lyon,IFR 19, CNRS, UMR 5167, F-69365 Lyon, France. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Fort, P (reprint author), RTH Laennec, Fac Med, CNRS, UMR 5167, 7 Rue Guillaume Paradin, FR-69372 Lyon, France. EM patrice.fort@sommeil.univ-lyon1.fr RI Luppi, Pierre-Herve/C-4333-2014; OI Luppi, Pierre-Herve/0000-0002-0503-423X; goutagny, romain/0000-0002-1268-533X NR 29 TC 19 Z9 19 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2005 VL 52 IS 3 BP 140 EP U10 DI 10.1159/000087560 PG 8 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 964WM UT WOS:000231911700006 PM 16110248 ER PT J AU Lee, ACH Bussey, TJ Murray, EA Saksida, LM Epstein, RA Kapur, N Hodges Jr Graham, KS AF Lee, ACH Bussey, TJ Murray, EA Saksida, LM Epstein, RA Kapur, N Hodges, JR Graham, KS TI Perceptual deficits in amnesia: challenging the medial temporal lobe 'mnemonic' view SO NEUROPSYCHOLOGIA LA English DT Article DE hippocampus; perirhinal cortex; memory; perception; visual discrimination ID PERIRHINAL CORTEX; FORNIX TRANSECTION; RHESUS-MONKEYS; SPATIAL MEMORY; HIPPOCAMPUS; RECOGNITION; LESIONS; HUMANS; REPRESENTATIONS; DISCRIMINATION AB Recent animal studies suggest that the medial temporal lobe (MTL), which is thought to subserve memory exclusively, may support non-mnemonic perceptual processes, with the hippocampus and perirhinal cortex contributing to spatial and object perception, respectively. There is, however, no support for this view in humans, with human MTL lesions causing prominent memory deficits in the context of apparently normal perception. We assessed visual discrimination in amnesic cases to reveal that while selective hippocampal damaged patients could discriminate faces, objects, abstract art and colour, they were significantly poorer in discriminating spatial scenes. By contrast, patients with MTL damage, including perirhinal cortex, were significantly impaired in discriminating scenes, faces, and to a lesser extent objects, with relatively intact discrimination of art and colour. These novel observations imply that the human MTL subserves both perceptual and mnemonic functions, with the hippocampus and perirhinal cortex playing distinct roles in spatial and object discrimination, respectively. (C) 2004 Elsevier Ltd. All rights reserved. C1 MRC, Cognit & Brain Sci Unit, Cambridge, England. Univ Cambridge, Dept Expt Psychol, Cambridge, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Cambridge, Addenbrookes Hosp, Neurol Unit, Cambridge, England. RP Lee, ACH (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge, England. EM andy.lee@mrc-cbu.cam.ac.uk RI Lee, Andy/A-1662-2008; Graham, Kim/A-1672-2010; Epstein, Russell/G-4517-2013; Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016; OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642; Graham, Kim/0000-0002-1512-7667; Lee, Andy/0000-0002-8546-5311 NR 37 TC 177 Z9 177 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2005 VL 43 IS 1 BP 1 EP 11 DI 10.1016/j.neuropsychologia.2004.07.017 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 874ZB UT WOS:000225388100001 PM 15488899 ER PT J AU Wood, JN Romero, SG Knutson, KM Grafman, J AF Wood, JN Romero, SG Knutson, KM Grafman, J TI Representation of attitudinal knowledge: role of prefrontal cortex, amygdala and parahippocampal gyrus SO NEUROPSYCHOLOGIA LA English DT Article DE social cognition; brain; prefrontal cortex; amygdala ID FRONTAL-SUBCORTICAL CIRCUITS; FUNCTIONAL MRI; AUTOMATIC ACTIVATION; PERIRHINAL CORTEX; EPISODIC MEMORY; NEURAL BASIS; BRAIN; FMRI; BEHAVIOR; TASK AB It has been proposed that behavior is influenced by representations of different types of knowledge: action representations, event knowledge, attitudes and stereotypes. Attitudes (representations of a concept or object and its emotional evaluation) allow us to respond quickly to a given stimulus. In this study, we explored the representation and inhibition of attitudes. We show that right dorsolateral prefrontal cortex mediates negative attitudes whereas left ventrolateral prefrontal cortex mediates positive attitudes. Parahippocampal regions and amygdala mediate evaluative processing. Furthermore, anxiety modulates right dorsolateral prefrontal activation during negative attitude processing. Inhibition of negative attitudes activates left orbitofrontal cortex: a region that when damaged is associated with socially inappropriate behavior in patients. Inhibition of positive attitudes activates a brain system involving right inferior frontal gyrus and bilateral anterior cingulate. Thus, we show that there are dissociable networks for the representation and inhibition of attitudes. Published by Elsevier Ltd. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Union Coll, Dept Psychol, Schenectady, NY 12308 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457; Knutson, Kristine/0000-0003-4626-4514 NR 92 TC 23 Z9 26 U1 4 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2005 VL 43 IS 2 BP 249 EP 259 DI 10.1016/j.neuropsychologia.2004.11.011 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 901BI UT WOS:000227257600010 PM 15707909 ER PT J AU Rosen, VM Sunderland, T Levy, J Harwell, A McGee, L Hammond, C Bhupali, D Putnam, K Bergeson, J Lefkowitz, C AF Rosen, VM Sunderland, T Levy, J Harwell, A McGee, L Hammond, C Bhupali, D Putnam, K Bergeson, J Lefkowitz, C TI Apolipoprotein E and category fluency: evidence for reduced semantic access in healthy normal controls at risk for developing Alzheimer's disease SO NEUROPSYCHOLOGIA LA English DT Article DE APOE; working memory; retrieval; switching; attention ID WORKING-MEMORY CAPACITY; CEREBRAL GLUCOSE-METABOLISM; E TYPE-4 ALLELE; VERBAL FLUENCY; FRONTAL-LOBE; SUBCORTICAL DEMENTIA; TEMPORAL-LOBE; HUNTINGTONS-DISEASE; FREE-RECALL; TASKS AB Two groups of non-demented individuals, who differed on genetic risk for Alzheimer's disease (AD) based on their apolipoprotein E (APOE) genotype, were tested on a category fluency task. Twenty epsilon4 carriers and twenty epsilon4 non-carriers were tape recorded while saying animal names for ten minutes. Five measures were examined: total names generated; total clusters; mean cluster size; mean within-cluster retrieval time; and mean between-cluster retrieval time. Groups were matched on age and education and scored as normal on a battery of psychometric tests. The epsilon4 carriers generated significantly fewer names and clusters, and took significantly longer to access clusters, when compared to the epsilon4 non-carriers. No group differences were found for cluster size or within-cluster retrieval times. We previously reported [Rosen, V. M., Bergeson, J. L., Putnam, K., Harwell, A., Sunderland, T. (2002). Working memory and apolipoprotein E: What's the connection? Neuropsychologia 40, 2226-2233] that the epsilon4 carriers in the present study scored significantly lower than the 64 non-carriers on a measure of working memory/attentional capacity [Operation Span Task, see Turner, M. L., Engle, R. W. (1989). Is working memory capacity task dependent? Journal of Memory and Language 28, 127-154]. In the present study, a significant negative relationship found between span performance and between-cluster retrieval times suggested that reduced attentional capacity may have negatively impacted semantic access for the epsilon4 carriers. Finally, we found significant relationships between a Trail Making Test [Reitan, R. M. (1992). Trail Making Test, manual for administration and scoring. Tucson, AZ: Reitan Neuropsychology Laboratory] "switch" measure (Form B-Form A) and three of the five fluency measures. The findings suggested that the epsilon4 carrier's reduced attentional capacity may have interfered with their covertly shifting attention among subcategories in the fluency task, resulting in fewer names and clusters generated and longer times to access clusters. (C) 2004 Elsevier Ltd. All rights reserved. C1 Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. NIMH, Geriatr Psychiat Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Rosen, VM (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. EM vrosen@syr.edu NR 80 TC 29 Z9 30 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2005 VL 43 IS 4 BP 647 EP 658 DI 10.1016/j.neuropsychologia.2004.06.022 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 902PU UT WOS:000227369800016 PM 15716154 ER PT J AU Johnson, LR Farb, C Morrison, JH McEwen, BS LeDoux, JE AF Johnson, LR Farb, C Morrison, JH McEwen, BS LeDoux, JE TI Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala SO NEUROSCIENCE LA English DT Review DE fear; postsynaptic density; non-genomic; plasticity ID POSTTRAUMATIC-STRESS-DISORDER; RAT BASOLATERAL AMYGDALA; LONG-TERM POTENTIATION; CALCIUM-CHANNELS; CONDITIONED FEAR; PTSD SYMPTOMS; CORTICOSTEROID ACTIONS; MEMORY CONSOLIDATION; SYNAPTIC PLASTICITY; DECLARATIVE MEMORY AB Glucocorticoids, released in high concentrations from the adrenal cortex during stressful experiences, bind to glucocorticoid receptors in nuclear and peri-nuclear sites in neuronal somata. Their classically known mode of action is to induce gene promoter receptors to alter gene transcription. Nuclear glucocorticoid receptors are particularly dense in brain regions crucial for memory, including memory of stressful experiences, such as the hippocampus and amygdala. While it has been proposed that glucocorticoids may also act via membrane bound receptors, the existence of the latter remains controversial. Using electron microscopy, we found glucocorticoid receptors localized to non-genomic sites in rat lateral amygdala, glia processes, presynaptic terminals, neuronal dendrites, and dendritic spines including spine organelles and postsynaptic membrane densities. The lateral nucleus of the amygdala is a region specifically implicated in the formation of memories for stressful experiences. These newly observed glucocorticoid receptor immunoreactive sites were in addition to glucocorticoid receptor immunoreactive signals observed using electron and confocal microscopy in lateral amygdala principal neuron and GABA neuron soma and nuclei, cellular domains traditionally associated with glucocorticoid immunoreactivity. In lateral amygdala, glucocorticoid receptors are thus also localized to non-nuclear-membrane translocation sites, particularly dendritic spines, where they show an affinity for postsynaptic membrane densities, and may have a specialized role in modulating synaptic transmission plasticity related to fear and emotional memory. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NYU, Ctr Neural Sci, New York, NY 10003 USA. CUNY Mt Sinai Sch Med, Dept Neurobiol, New York, NY 10029 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. NYU, NIMH, Conte Ctr Neurosci Fear & Anxiety, Ctr Neural Sci, New York, NY 10003 USA. RP Johnson, LR (reprint author), NYU, Ctr Neural Sci, 4 Washington Pl, New York, NY 10003 USA. EM Johnson@cns.nyu.edu RI Morrison, John/F-9229-2012 FU NIMH NIH HHS [MH58911] NR 111 TC 112 Z9 113 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 136 IS 1 BP 289 EP 299 DI 10.1016/j.neuroscience.2005.06.050 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 985OH UT WOS:000233386900026 PM 16181741 ER PT J AU Martinez, A Otal, R Sieber, BA Ibanez, C Soriano, E AF Martinez, A Otal, R Sieber, BA Ibanez, C Soriano, E TI Disruption of ephrin-A/EphA binding alters synaptogenesis and neural connectivity in the hippocampus SO NEUROSCIENCE LA English DT Article DE anterograde tracers; transgenic mice; hippocampal afferents; mossy fibers; calbindin ID RECEPTOR TYROSINE KINASES; CENTRAL-NERVOUS-SYSTEM; GROWTH CONE COLLAPSE; AXON GUIDANCE; THALAMOCORTICAL PROJECTIONS; DENTATE-GYRUS; EPHA RECEPTORS; TOPOGRAPHIC PROJECTION; NEURITE OUTGROWTH; GENE-EXPRESSION AB Ephrins are guidance cues that modulate axonal growth and the subsequent axonal topographic maps in many regions of the CNS. Here we studied the functional roles of ephrin-A/EphA interactions in the layer-specific pattern of axonal projections in the hippocampus by disrupting the ephrin-A signaling by over-expression of a soluble EphA receptor. Tracing experiments in EphA5-Fc over-expressing mice revealed that reduction of ephrin-A/EphA interactions did not affect the proper distribution of the main hippocampal afferents, i.e. entorhinal and commissural projections. However, further ultrastructural analyses showed a reduction in the density of synaptic terminals in the antorhinal and commissural termination layers in these mice. In addition, using anti-calbindin antibodies, we analyzed the dentate mossy fiber projections following disruption of ephrin-A/EphA interactions throughout developing hippocampus. While the main mossy fiber bundle appeared normal, the infrapyramidal bundle formed longer projections that established ectopic contacts in these transgenic mice. Later, the expected specific pruning of the infrapyramidal bundle was not observed at adult stages. Ultrastructural analyses confirmed a higher number of mossy fiber terminals in the infrapyramidal bundle in adult EphA5-Fc transgenic mice and showed that these terminals were larger and established a greater number of contacts than in controls. Our results demonstrate that ephrin-A/EphA interactions regulate the synaptogenesis of hippocampal afferents and the proper development and refinement of granule cell projections. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Barcelona, Dept Cell Biol, Neuronal Dev & Regenerat Grp S1A1, E-08028 Barcelona, Spain. NIMH, MCN, DNBBS, Bethesda, MD 20892 USA. Karolinska Inst, Dept Neurosci, Div Neurophysiol & Behav, Stockholm, Sweden. RP Martinez, A (reprint author), Univ Barcelona, Dept Cell Biol, Neuronal Dev & Regenerat Grp S1A1, Barcelona Sci Pk,Josep Samitier 1-5, E-08028 Barcelona, Spain. EM albertm@pcb.ub.es NR 68 TC 20 Z9 20 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 135 IS 2 BP 451 EP 461 DI 10.1016/j.neuroscience.2005.06.052 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 970OM UT WOS:000232319500014 PM 16112477 ER PT J AU Bratincsak, A Palkovits, M AF Bratincsak, A Palkovits, M TI Evidence that peripheral rather than intracranial thermal signals induce thermoregulation SO NEUROSCIENCE LA English DT Article DE thermoregulation; peripheral thermosensation; preoptic area; skin thermoreceptors; c-fos in situ hybridization ID BODY-TEMPERATURE; CELLULAR MECHANISMS; NERVOUS-SYSTEM; BRAIN-AREAS; THERMOSENSITIVITY; NEURONS; STRESS; FOS; HYPOTHALAMUS; RECEPTORS AB Numerous effector mechanisms have been discovered, which change body temperature and thus serve to maintain the thermal integrity of homeothermic animals. These mechanisms are driven by thermal signals that are processed by neurons in the hypothalamic preoptic area. To keep a tight control over body temperature, these neurons have to receive accurate thermal information. Although in vitro studies have shown the direct thermosensitive ability of neurons in the preoptic area, other observations suggest the existence of peripheral thermosensation and an ascending thermal pathway to the thermoregulatory center. Direct evidences for either one, or both are still missing. In the present study, brain, rectal, subcutaneous and skin surface temperatures were measured during 15, 30, 60 and 120 min of cold exposure (4 degrees C) in rats and compared with neuronal activation due to cold stress shown by c-fos in situ hybridization histochemistry. Subcutaneous and skin surface temperatures dropped continuously throughout the 120 min of cold exposure by 1.4 degrees C and 6.5 degrees C, respectively. However, during the first 30 min, brain and rectal temperatures increased by 0.3 degrees C and 0.25 degrees C, respectively, and even after 60 min of cold stress, brain temperature did not decrease under the level measured at 0 min. Since the brain temperature did not decrease, it is unlikely that intracranial thermoreceptors are involved in the transmission of "cold" thermal signal to induce thermoregulation. At 30 min of cold exposure, neurons in all known thermoregulatory areas (like the ventrolateral part of the medial preoptic nucleus, the lateral retrochiasmatic area, the lateral parabrachial nucleus and the peritri-geminal nucleus) were already maximally activated. These observations clearly indicate that the activation of neurons in the preoptic and several other thermoregulatory nuclei is induced in vivo by thermal signals originating in the periphery, and not in the CNS. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Neuromorphol Lab, H-1085 Budapest, Hungary. Hungarian Acad Sci, Budapest, Hungary. RP Bratincsak, A (reprint author), NIMH, Genet Lab, NIH, 36 Convent Dr,Bldg 36,Room 3D06, Bethesda, MD 20892 USA. EM bratiandris@yahoo.com RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 30 TC 26 Z9 27 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 135 IS 2 BP 525 EP 532 DI 10.1016/j.neuroscience.2005.06.028 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 970OM UT WOS:000232319500020 PM 16125855 ER PT J AU Yang, J Shen, J AF Yang, J Shen, J TI In vivo evidence for reduced cortical glutamate-glutamine cycling in rats treated with the antidepressant/antipanic drug phenelzine SO NEUROSCIENCE LA English DT Article DE amino acid neurotransmitters; 4-aminobutyrate transaminase; glutamate neurotransmission; GABA; in vivo magnetic resonance spectroscopy ID GAMMA-AMINOBUTYRIC-ACID; GABA-TRANSAMINASE INHIBITION; MONOAMINE-OXIDASE ACTIVITY; C-13 NMR; HUMAN BRAIN; NEUROTRANSMITTER GLUTAMATE; AMINOOXYACETIC ACID; GLUCOSE-UTILIZATION; HIPPOCAMPAL SLICES; PREFRONTAL CORTEX AB Converging evidence has indicated that hyperglutamatergic activity and GABAergic dysfunction may play important roles in the neurobiology and treatment of depression and other mood disorders. In this study, in vivo H-1[C-13] magnetic resonance spectroscopy was used to quantify the effects of acute phenelzine administration on cortical energetics, glutamate neurotransmission, and GABA synthesis flux. The time-resolved kinetics of cortical [4-C-13] glutamate, [4-C-13]glutamine, and [2-C-13]GABA turnover from i.v.-infused [1,6-C-13(2)]glucose was measured at 11.7 T in alpha-chloralose anesthetized rats four hours after phenelzine treatment (10 mg/kg, i.p.) and in non-treated controls. The rate of the tricarboxylic acid cycle flux was not affected by phenelzine treatment compared with the non-treated group (0.46. +/- 0.05 vs. 0.50 +/- 0.05 mu mol/g/min, respectively). The rate of the glutamate-glutamine cycling flux between neurons and glia in the phenelzine-treated group was significantly reduced (from 0.16 +/- 0.04 to 0.10 +/- 0.03 mu mol/g/min), providing in vivo evidence that phenelzine attenuates glutamate neurotransmission. Following phenelzine treatment, the cortical GABA concentration increased significantly (from 1.02 +/- 0.17 to 2.30 +/- 0.26 mu mol/g), while the GABA synthesis flux was unchanged (from 0.07 +/- 0.02 to 0.06 +/- 0.02 mu mol/g/min). The possible role of augmented GABAergic function resulting from elevated GABA levels in the observed modulatory effect of phenelzine on the glutamate-glutamine cycling flux was discussed. The reduced glutamate-glutamine cycling flux observed in this study suggests that, in addition to its effects on monoaminergic and GABAergic systems, the attenuation of glutamate neurotransmission resulting from phenelzine administration may also contribute to its efficacy in the treatment of depression. This study is the first demonstration that the glutamate-glutamine cycling flux, which can be measured non-invasively in the human brain in vivo, was altered due to the action of a psychotropic drug. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Mol Imaging Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Mood & Anxiety Disorders Program, Bldg 10,Room 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov NR 75 TC 45 Z9 48 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 135 IS 3 BP 927 EP 937 DI 10.1016/j.neuroscience.2005.06.067 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 977YK UT WOS:000232839200024 PM 16154287 ER PT J AU Qin, M Kang, J Smith, CB AF Qin, M Kang, J Smith, CB TI A null mutation for Fmr1 in female mice: Effects on regional cerebral metabolic rate for glucose and relationship to behavior SO NEUROSCIENCE LA English DT Article DE functional activity; rCMR(glc); open field activity; passive avoidance; audiogenic seizures; acoustic startle ID FRAGILE-X-SYNDROME; KNOCKOUT MICE; MENTAL-RETARDATION; ESTROUS-CYCLE; RAPHE NUCLEI; MOUSE MODEL; IMPAIRMENT; PHENOTYPE; SEIZURES; STIMULI AB As a measure of functional activity we determined regional cerebral metabolic rate for glucose (rCMR(glc)) in adult, female wild type and fragile X (Fmr1 null) mice homozygous and heterozygous for the null mutation. To ascertain if the sexes differ with respect to the severity of the effects of the mutation we compared our results with results of our previous study on male Fmr1 null mice [Qin M, Kang J, Smith CB (2002) Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation. Proc Natl Acad Sci USA 99:15758-15763.]. In contrast to the male Fmrl null mouse, rCMRglc was unchanged in the homozygous female except in the dorsal raphe where rCMR(glc) was increased by 36%. There were no differences in rCMR(glc) between heterozygous and wild type female mice. We compared male and female mice for effects of the null mutation on behavior. We found that the female Fmrl null mouse is similar to the male with deficits in performance on a passive avoidance task, general hyperactivity, and increased susceptibility to audiogenic seizures. Both homozygous and heterozygous female mice exhibited hyperactivity and increased susceptibility to seizures, whereas only the homozygous mice had a deficit on the passive avoidance test. Male Fmrl null mice had a tendency for lower anxiety-like behavior in an open field, whereas this was not evident in females. Compared with male wild type, male Fmrl null mice also had a diminished acoustic startle response at higher stimulus intensities, whereas all three female genotypes had responses similar to those of male Fmrl null mice. Whether estrogen affords female Fmrl null mice some protection from the effects of the mutation remains to be determined. Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Unit Neuroadapatat & Prot Metab, Lab Cerebral Metab, US Publ Hlth,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), NIMH, Unit Neuroadapatat & Prot Metab, Lab Cerebral Metab, US Publ Hlth,Dept Hlth & Human Serv, 10 Ctr Dr,Room 2D54, Bethesda, MD 20892 USA. EM beebec@intra.nimh.nih.gov FU Intramural NIH HHS NR 34 TC 35 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 135 IS 3 BP 999 EP 1009 DI 10.1016/j.neuroscience.2005.06.081 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 977YK UT WOS:000232839200031 PM 16154294 ER PT J AU Perlman, WR Matsumoto, M Beltaifa, S Hyde, TM Saunders, RC Webster, MJ Rubinow, DR Kleinman, JE Weickert, CS AF Perlman, WR Matsumoto, M Beltaifa, S Hyde, TM Saunders, RC Webster, MJ Rubinow, DR Kleinman, JE Weickert, CS TI Expression of estrogen receptor alpha exon-deleted mRNA variants in the human and non-human primate frontal cortex SO NEUROSCIENCE LA English DT Article DE hormone; brain; monkey; isoform; splicing; gene expression ID HUMAN BREAST-CANCER; STEROID-HORMONE RECEPTORS; NONSENSE-MEDIATED DECAY; WILD-TYPE; ER-ALPHA; GENE-EXPRESSION; CELL-LINES; TRANSCRIPTIONAL ACTIVATION; PREFRONTAL CORTEX; CEREBRAL-CORTEX AB Although estrogen receptor alpha (ER alpha) mRNA has been detected in the primate frontal cortex, the types of ERa transcripts expressed, including exon-deleted variants (A), have not been determined in the monkey or human frontal cortex. Because the types of ERa mRNA expressed in brain could define neuronal responses to estrogens, we examined the transcript pool of ER alpha mRNAs expressed in normal adult and developing human and macaque frontal cortex. We reverse transcribed total RNA from the postmortem frontal cortex of 29 normal adult humans, 12 rhesus macaques, and 19 people ranging from infants to adults and employed two rounds of nested polymerase chain reaction (PCR) to generate ERa products spanning the coding domain. In a third nested PCR, we used primers specific for novel sequences of exon-exon junctions created when whole exons are missing. By sequencing PCR products, we detected 60 instances of 12 distinct Delta ER alpha mRNAs in adult humans and 94 instances of 13 distinct Delta ER alpha. mRNAs in monkeys in differing patterns from one individual to another. In adult humans, 83% of individuals expressed at least 1 Delta ER alpha mRNA variant, and 100% of the monkeys expressed at least 1 Delta ER alpha mRNA variant. The single Delta 2, Delta 5, and Delta 7 variants were frequently expressed in both human and monkey frontal cortex, Delta 3 variants were rare in both species, and Delta 6 variants were more frequently expressed in monkeys. In both species, we detected double, triple and quadruple Delta s, but these were less common than single Delta s. The pattern of human variant expression did not appear to change dramatically as a function of age. These findings imply the potential to produce different ER alpha proteins in frontal cortex, possibly with altered structure and function which may have physiological relevance for gene transcription by virtue of altered functional interactions with each other, other steroid hormone receptors, and genomic DNA. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Clin Brain Disorders Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIMH, Lab Neuropsychol, Intramural Res Program, NIH,US Dept HHS, Bethesda, MD 20892 USA. Yamanouchi Pharmaceut Co Ltd, Genom Res, Tsukuba, Ibaraki 3058585, Japan. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. RP Perlman, WR (reprint author), NIMH, Clin Brain Disorders Branch, NIH, US Dept HHS, 10 Ctr Dr,Room 4N313C, Bethesda, MD 20892 USA. EM perimanw@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; Matsumoto, Mitsuyuki/G-3207-2012 OI Matsumoto, Mitsuyuki/0000-0002-1172-2354 FU NICHD NIH HHS [N01-HD-1-3138] NR 84 TC 37 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 134 IS 1 BP 81 EP 95 DI 10.1016/j,neuroscience.2005.03.055 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 949SK UT WOS:000230808200009 PM 15964702 ER PT J AU Miyachi, S Hasegawa, YT Gerfen, CR AF Miyachi, S Hasegawa, YT Gerfen, CR TI Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum SO NEUROSCIENCE LA English DT Article DE basal ganglia; gene regulation; glutamate; corticostriatal; neuronal plasticity ID LONG-TERM POTENTIATION; DOPAMINE-DEPLETED STRIATUM; MOTOR CORTEX; C-FOS; CORTICOSTRIATAL PROJECTIONS; RAT NEOSTRIATUM; SQUIRREL-MONKEY; REGULATED GENE; MACAQUE MONKEY; BASAL GANGLIA AB The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons. Cortical motor areas were stimulated through implanted electrodes in awake, behaving rats, and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos and arc was analyzed in the striatum with in situ hybridization histochemistry. In the first experiment, unilateral stimulation of the medial agranular cortex, orofacial region of the lateral agranular cortex or the forelimb region of the lateral agranular cortex resulted in IEG induction in the striatum, which was restricted to the topographically related area receiving input from the stimulated cortical area. In a second experiment, stimulation parameters were altered, including frequency, number of pulses/train, and number of trains/s. These parameters did not have a significant effect on IEG induction. Notably, in some cases, in which there was IEG induction not only in the stimulated cortical region, but also in the homologous area in the contralateral hemisphere, very robust IEG induction was observed in the striatum. In a third experiment, the orofacial regions of the lateral agranular cortex of both hemispheres were stimulated coincidently. All of these animals showed robust striatal IEG induction. This IEG induction was attenuated by pretreatment with an NMDA antagonist IVIK-801. In a fourth experiment, we tested whether the coincidence of bilateral cortical stimulation contributed to the efficacy of striatal IEG induction. Either alternating stimulation or coincident stimulation of non-homologous cortical regions produced significantly lower striatal IEG induction than obtained with coincident stimulation of homologous cortical areas. Enhanced striatal IEG induction occurred in indirect striatal neurons, labeled with enkephalin, but was also present in a large number of enkephalin-negative neurons, most of which are likely direct pathway neurons. These results suggest that regional and temporal convergence of cortical inputs enhances striatal IEG induction. Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Neuroanat Sect, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Gerfen, CR (reprint author), NIMH, Neuroanat Sect, Lab Syst Neurosci, Bldg 35,Room 3A-1000,35 Convent Dr, Bethesda, MD 20892 USA. EM miyachi@tmin.ac.jp; yt-hasegawa@aist.go.jp; gerfenc@mail.nih.gov NR 47 TC 9 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 134 IS 3 BP 1013 EP 1022 DI 10.1016/j.neuroscience.2005.02.051 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 959BF UT WOS:000231491200027 PM 15978736 ER PT J AU He, B Counts, SE Perez, SE Hohmann, JG Koprich, JB Lipton, JW Steiner, RA Crawley, JN Mufson, EJ AF He, B Counts, SE Perez, SE Hohmann, JG Koprich, JB Lipton, JW Steiner, RA Crawley, JN Mufson, EJ TI Ectopic galanin expression and normal galanin receptor 2 and galanin receptor 3 mRNA levels in the forebrain of galanin transgenic mice SO NEUROSCIENCE LA English DT Article DE neuropeptides; galaninergic; galanin receptors; mouse; plasticity ID CENTRAL-NERVOUS-SYSTEM; BETA-HYDROXYLASE GENE; CELL-SPECIFIC EXPRESSION; RAT BASAL FOREBRAIN; ACETYLCHOLINE-RELEASE; VENTRAL HIPPOCAMPUS; TREATED RATS; CLONED HUMAN; NEURONS; IMMUNOREACTIVITY AB The functional interactions of the neuropeptide galanin (GAL) occur through its binding to three G protein-coupled receptor subtypes: galanin receptor (GALR) 1, GALR2 and GALR3. Previously, we demonstrated that GALR1 mRNA expression was increased in the CA1 region of the hippocampus and discrete hypothalamic nuclei in galanin transgenic (GAL-tg) mice. This observation suggested a compensatory adjustment in cognate receptors in the face of chronic GAL exposure. To evaluate the molecular alterations to GALR2 and GALR3 in the forebrain of GAL overexpressing mice, we performed complementary quantitative, real-time PCR (qPCR), in situ hybridization, and immunohistochemistry in select forebrain regions of GAL-tg mice to characterize the neuronal distribution and magnitude of GAL mRNA and peptide expression and the consequences of genetically manipulating the neuropeptide GAL on the expression of GALR2 and GALR3 receptors. We found that GAL-tg mice displayed dramatic increases in GAL mRNA and peptide in the frontal cortex, posterior cortex, hippocampus, septal diagonal band complex, amygdala, piriform cortex, and olfactory bulb. Moreover, there was evidence for ectopic neuronal GAL expression in forebrain limbic regions that mediate cognitive and affective behaviors, including the piriform and entorhinal cortex and amygdala. Interestingly, regional qPCR analysis failed to reveal any changes in GALR2 or GALR3 expression in the GAL-tg mice, suggesting that, contrary to GALR1, these receptor genes are not under ligand-mediated regulatory control. The GAL-tg mouse model may provide a useful tool for the investigation of GAL ligand-receptor relationships and their role in normal cognitive and affective functions as well as in the onset of neurological disease. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Univ Washington, Neurobiol & Behav Program, Dept Physiol & Biophys, Seattle, WA 98195 USA. Univ Washington, Neurobiol & Behav Program, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Neurobiol & Behav Program, Dept Zool, Seattle, WA 98195 USA. NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. RP Mufson, EJ (reprint author), Rush Univ, Med Ctr, Dept Neurol Sci, 1735 W Harrison St, Chicago, IL 60612 USA. EM emufson@rush.edu FU NIA NIH HHS [AG10688, AG05136, AG09466]; NICHD NIH HHS [HD27142]; PHS HHS [U54 12629] NR 50 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 133 IS 2 BP 371 EP 380 DI 10.1016/j.neuroscience.2005.01.068 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 934OO UT WOS:000229718300003 PM 15885921 ER PT J AU Webster, MJ O'Grady, J Kleinman, JE Weickert, CS AF Webster, MJ O'Grady, J Kleinman, JE Weickert, CS TI Glial fibrillary acidic protein mRNA levels in the cingulate cortex of individuals with depression, bipolar disorder and schizophrenia SO NEUROSCIENCE LA English DT Article DE astrocytes; mental illness; glia; white matter ID DORSOLATERAL PREFRONTAL CORTEX; STROOP TASK-PERFORMANCE; SEVERE MENTAL-ILLNESS; WHITE-MATTER; MAJOR DEPRESSION; RAT-BRAIN; CEREBRAL-CORTEX; MOOD DISORDERS; NEUROPATHOLOGY-CONSORTIUM; NEURONAL DENSITY AB Recent studies have shown a decrease in glial number and glial fibrillary acidic protein (GFAP) levels in the frontal and cingulate cortices of individuals with mood disorders and schizophrenia. In an attempt to verify and expand these findings we examined GFAP messenger ribonucleic acid (mRNA) levels in postmortem sections of the anterior cingulate cortex (ACC) from the Stanley Neuropathology Consortium (SNC). The consortium consists of 15 cases in each of four groups (schizophrenia, bipolar disorder, non-psychotic depression and unaffected controls). By in situ hybridization, we found higher levels of GFAP mRNA in white matter and at the pial surface as compared with gray matter levels in all cases. In the white matter of ACC we detected a significant effect of diagnosis (P < 0.04) with GFAP mRNA levels decreased in individuals with schizophrenia and bipolar disorder as compared with normal controls. In the gray matter there was a significant effect of layer (P < 0.01) with the highest levels of GFAP mRNA in layer VI in all groups. As in the white matter, the mean GFAP mRNA levels were decreased in individuals with schizophrenia and bipolar disorder as compared with the unaffected controls, however the difference failed to reach statistical significance. Thus, astrocytes positive for GFAP may contribute to the decrease in glial density previously described in subjects with major mental illness, however the relative contribution of astrocytes may vary with diagnosis. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Lab Brain Res, Bethesda, MD 20814 USA. NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20894 USA. RP Webster, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Lab Brain Res, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM websterm@stanleyresearch.org RI Shannon Weickert, Cynthia/G-3171-2011 NR 95 TC 104 Z9 114 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 133 IS 2 BP 453 EP 461 DI 10.1016/j.neuroscience.2005.02.037 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 934OO UT WOS:000229718300010 PM 15885920 ER PT J AU Yabe, T Kanemitsu, K Sanagi, T Schwartz, JP Yamada, H AF Yabe, T Kanemitsu, K Sanagi, T Schwartz, JP Yamada, H TI Pigment epithelium-derived factor induces pro-survival genes through cyclic AMP-responsive element binding protein and nuclear factor kappa B activation in rat cultured cerebellar granule cells: Implication for its neuroprotective effect SO NEUROSCIENCE LA English DT Article DE pigment epithelium-derived factor; PEDF; prosurvival genes; neuronal apoptosis; transcription factors; signal transduction pathway ID GROWTH-FACTOR-I; TRANSCRIPTION FACTORS; NEUROTROPHIC FACTOR; MEDIATED APOPTOSIS; NEURONAL SURVIVAL; OXIDATIVE STRESS; BCL-2 HOMOLOG; LOW-POTASSIUM; FACTOR PEDF; CREB AB Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cell neurons (CGCs) against apoptosis induced by K+ and serum deprivation. However, the precise mechanism of this protection remains unknown. We recently reported that the transcription factor nuclear factor kappa B (NF-kappa B) is activated in PEDF-treated CGCs. Although it is well known that NF-kappa B blocks apoptotic cell death through the induction of pro-survival factors, the effects of PEDF on the expression of these factors are not fully understood. In this study, we employed the use of reverse transcriptase-polymerase chain reaction to analyze the gene expression of certain pro-survival genes and found that genes such as c-IAPI, c-IAP2, FLIPs, A1/BfI-1 and Mn-SOD were induced in PEDF-treated neurons. On the other hand, no induction was observed of the pro-apoptotic Bcl-2 family members Bax and Bid at any time from 3 to 24 h following PEDF addition. Furthermore, phosphorylation of cyclic AMP-responsive element binding protein (CREB) and increment of nuclear cyclic AMP-response element (CRE)-like DNA binding were observed in PEDF-treated CGCs. The anti-apoptotic effect of PEDF was blocked by overexpression of dominant negative CREB or a mutated form of I kappa B alpha. These results suggested that induction of both CRE- and NF-kappa B-dependent genes is required for the observed neuroprotective effects of PEDF on CGCs. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Kitasato Inst, Kitasato Inst Life Sci, Minato Ku, Tokyo 1088641, Japan. Kitasato Inst, Grad Sch Infect Control Sci, Minato Ku, Tokyo 1088641, Japan. NINDS, Neurotroph Factors Sect, NIH, Bethesda, MD 20892 USA. Kitasato Inst, Oriental Med Res Ctr, Tokyo 108, Japan. RP Yabe, T (reprint author), Kitasato Inst, Kitasato Inst Life Sci, Minato Ku, 5-9-1,Shirokane, Tokyo 1088641, Japan. EM tyabe@lisci.kitasato-u.ac.jp NR 57 TC 23 Z9 24 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 133 IS 3 BP 691 EP 700 DI 10.1016/j.neuroscience.2005.03.007 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 939HZ UT WOS:000230064600008 PM 15893882 ER PT J AU Gong, JP Liu, QR Zhang, PW Wang, Y Uhl, GR AF Gong, JP Liu, QR Zhang, PW Wang, Y Uhl, GR TI Mouse brain localization of the protein kinase C-enhanced phosphatase 1 inhibitor kepi (kinase C-enhanced PP1 inhibitor) SO NEUROSCIENCE LA English DT Article DE brain distribution; immunohistochemistry; protein phosphorylation; PP1 inhibitor; protein kinase C; protein phosphatase 1 ID RABBIT SKELETAL-MUSCLE; IMMUNOCYTOCHEMICAL LOCALIZATION; DOPAMINE-RECEPTOR; SPINAL-CORD; PKC; PHOSPHORYLATION; ISOFORM; POLYPEPTIDE; DARPP-32; REGIONS AB We recently identified the protein kinase C-enhanced protein phosphatase 1 (PP1) inhibitor KEPI based on its morphine-induced upregulation in striatum. Regulation of protein serine/threonine dephosphorylation by PP1 can modulate important brain signaling pathways. To improve understanding of KEPI's role in the brain, we have developed anti-KEPI sera in rabbits immunized with a hemocyanin conjugate of KEPI residues 66-80, characterized the specificity that this serum provides, mapped the distribution of immunoreactive KEPI (KEPI) in mouse brain, rat dorsal root ganglia and striatal cultures and documented KEPI binding to PP1 in vitro. Staining is found in apparently neuronal processes and, often less intensely, in neuronal perikarya in primary cultures and in neurons and neuronal elements from a number of brain regions. iKEPI fiber/terminal patterns are relatively densely distributed in striatum, nucleus accumbens, septum, bed nucleus of the stria terminals, hippocampus, paraventricular thalamus, ventromedial hypothalamus, interpeduncular nucleus, raphe nuclei, nucleus caudalis of the spinal tract of the trigeminal and dorsal horn of the spinal cord. iKEPI-positive cell bodies lie in the nucleus accumbens, striatum, lateral septal nucleus, granular layer of dentate gyrus, interpeduncular nucleus, dorsal root ganglia and cerebellar vermis. These expression patterns point to possible roles for KEPI in regulating protein dephosphorylation by inhibiting PP1 activities in a number of brain pathways likely to use several different neurotransmitters and to participate in a number of brain functions. Dense KEPI immunoreactivity in nucleus accumbens perikarya, combined with evidence for its regulation by opiates, supports possible roles for KEPI in molecular signal transduction pathways important for drug reward and addiction. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIDA, NIH, DHHS, Baltimore, MD 21224 USA. RP Uhl, GR (reprint author), NIDA, NIH, DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 NR 35 TC 12 Z9 13 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 132 IS 3 BP 713 EP 727 DI 10.1016/j.neuroscience.2004.11.052 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 921XB UT WOS:000228797800018 PM 15837133 ER PT J AU Brazel, CY Nunez, JL Yang, Z Levison, SW AF Brazel, CY Nunez, JL Yang, Z Levison, SW TI Glutamate enhances survival and proliferation of neural progenitors derived from the subventricular zone SO NEUROSCIENCE LA English DT Article DE apoptosis; glutamate receptors; regeneration; stem cells; degeneration ID HYPOXIA-ISCHEMIA; OLIGODENDROCYTE PROGENITORS; WHITE-MATTER; NEONATAL RAT; STEM-CELLS; RECEPTORS; INJURY; HYPOXIA/ISCHEMIA; HISTOPATHOLOGY; SYSTEM AB Extracellular glutamate levels increase as a consequence of perinatal hypoxia/ischemia, causing the death of neurons and oligodendrocytes. Precursors in the subventricular zone (SVZ) also die following perinatal hypoxia/ischemia; therefore we hypothesized that glutamate would stimulate the death of neural precursors. Here we demonstrate using calcium imaging that SVZ derived neural stem/progenitor cells respond to both ionotropic and metabotropic excitatory amino acids. Therefore, we tested the effects of high levels of glutamate receptor agonists on the proliferation, survival, and differentiation of SVZ derived neural stem/progenitor cells in vitro. We show that high levels of glutamate, up to 1 mM, are not toxic to neural precursor cultures. In fact, stimulation of either the kainate receptor or group 2 metabotropic glutamate receptors (group 2 mGluR) reduces basal levels of apoptosis and increases neural precursor proliferation. Furthermore, group 2 mGluR activation expands the number of multipotent progenitor cells present in these cultures while maintaining equivalent mature cell production. We conclude that the glutamate released following perinatal hypoxia/ischemia may act to acutely promote the proliferation of multipotent precursors in the subventricular zone. (C) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 UMDMJ, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07101 USA. NIA, Stem Cell Biol Unit, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Michigan State Univ, Dept Psychol, Program Neurosci, E Lansing, MI 48824 USA. Penn State Univ, Dept Neural & Behav Sci, Coll Med, Hershey, PA 17033 USA. RP Levison, SW (reprint author), UMDMJ, New Jersey Med Sch, Dept Neurol & Neurosci, 185 S Orange Ave,H-506, Newark, NJ 07101 USA. EM levisosw@umdnj.edu OI Levison, Steven/0000-0002-1264-7309 FU NICHD NIH HHS [HD 30705, N01-HD-2-3144]; NIMH NIH HHS [MH 59950, R01 MH059950] NR 33 TC 104 Z9 113 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 131 IS 1 BP 55 EP 65 DI 10.1016/j.neuroscience.2004.10.038 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 896RM UT WOS:000226951200005 PM 15680691 ER PT J AU Weickert, CS Kittell, DA Saunders, RC Herman, MM Horlick, RA Kleinman, JE Hyde, TM AF Weickert, CS Kittell, DA Saunders, RC Herman, MM Horlick, RA Kleinman, JE Hyde, TM TI Basic fibroblast growth factor and fibroblast growth factor receptor-1 in the human hippocampal formation SO NEUROSCIENCE LA English DT Article DE bFGF; FGF-2; FGFR1; flg; neurogenesis; neurotrophic ID CENTRAL-NERVOUS-SYSTEM; ADULT-RAT BRAIN; ANTISENSE MESSENGER-RNA; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; DENTATE GYRUS; NEUROFIBRILLARY TANGLES; TISSUE DISTRIBUTION; OXIDATIVE STRESS; SENILE PLAQUES AB Basic fibroblast growth factor (bFGF) is an important mitogen and neurotrophic factor that binds and signals through the high-affinity receptor, fibroblast growth factor receptor I (FGFR1). However, only a limited amount of information is available concerning the molecular forms and anatomical distribution of fibroblast growth factors (FGFs) in the normal human brain. We found multiple bFGF and FGFR1 mRNA transcripts which vary in expression pattern across human brain regions. Using in situ hybridization and immunohistochemistry, we localized bFGF and FGFR1 mRNA and protein to cells in the normal adult human hippocampus and caudal entorhinal cortex (ERC). The majority of pyramidal neurons contained FGFR1 mRNA and protein in the mesial temporal lobe, with neurons in the CA2/CA3 region demonstrating the highest levels of FGFR1 mRNA. In contrast to FGFR1, bFGF mRNA expression was detected at very low levels in a small fraction of the neurons in the human hippocampus and caudal ERC. While bFGF mRNA may be expressed at low levels in neurons, bFGF-immunopositive cells with astrocytic features were detected throughout the mesial temporal lobe in rats, monkeys and humans. bFGF immunoreactive processes are found traversing the dentate gyrus, and bFGF immunoreactive cells are found in the neurogenic subgranular zone in all three mammalian species studied. The anatomical distribution of these two FGF family members suggests that bFGF is endogenously positioned to be involved in ongoing neurogenesis in the adult hippocampus, and that FGF trophic signaling to differentiated neurons could involve the release of astrocytic bFGF acting on neuronal FGFR1 in the normal adult human hippocampus. Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Neuropathol Sect, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Pharmacopeia Inc, Dept Biol, Cranbury, NJ 08512 USA. RP Weickert, CS (reprint author), NIMH, Neuropathol Sect, Clin Brain Disorders Branch, Intramural Res Program,NIH, 9000 Rockville Pike,Bldg 10,Room 4N308-A, Bethesda, MD 20892 USA. EM shannowc@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011 NR 73 TC 22 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 131 IS 1 BP 219 EP 233 DI 10.1016/j.neuroscience.2004.09.070 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 896RM UT WOS:000226951200019 PM 15680705 ER PT J AU Zhang, L Slikhareva, M Barker, JL Maric, D Hao, Y Chang, YH Ma, W O'Shaughnessy, T Rubinow, DR AF Zhang, L Slikhareva, M Barker, JL Maric, D Hao, Y Chang, YH Ma, W O'Shaughnessy, T Rubinow, DR TI Direct binding of estradiol enhances Slack (sequence like a calcium-activated potassium channel) channels' activity SO NEUROSCIENCE LA English DT Article DE estrogen; ion channel; neuron; electrophysiology; non-genomic; estrogen receptor ID MEMBRANE ESTROGEN-RECEPTORS; PROTEIN-COUPLED RECEPTORS; CENTRAL-NERVOUS-SYSTEM; HYPOTHALAMIC NEURONS; GENE-TRANSCRIPTION; ALZHEIMERS-DISEASE; MESSENGER-RNA; BETA-SUBUNIT; RAT; KINASE AB 17beta-Estradiol (E2) is a major neuroregulator, exerting both genomic and non-genomic actions. E2 regulation of Slack (sequence like a calcium-activated potassium channel) potassium channels has not been identified in the CNS. We demonstrate E2-induced activation of Slack channels, which display a unitary conductance of about 60 pS, are inhibited by intracellular calcium, and are abundantly expressed in the nervous system. In lipid bilayers derived from rat cortical neuronal membranes, E2 increases Slack open probability and appears to decrease channel inactivation. Additionally, E2 binds to the Slack channel and activates outward currents in human embryonic kidney-293 cells that express Slack channels but not classical estrogen receptors (i.e. ERa or ERP). Neither E2-induced activation nor the binding intensity of E2 to the Slack channel is blocked by tamoxifen, an ER antagonist/agonist. Thus, E2 activates a potassium channel, Slack, through a non-traditional membrane binding site, adding to known non-genomic mechanisms by which E2 exerts pharmacological and toxicological effects in the CNS. Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, NIH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, L (reprint author), NIMH, NIH, Behav Endocrinol Branch, Bldg 10,Room 65340,MSC 1276, Bethesda, MD 20892 USA. EM lezhang@usuhs.mil NR 55 TC 11 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 131 IS 2 BP 275 EP 282 DI 10.1016/j.neuroscience.2004.10.042 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 901BQ UT WOS:000227258400003 PM 15708472 ER PT J AU Wisor, JP Edgar, DM Yesavage, J Ryan, HS McCormick, CM Lapustea, N Murphy, GM AF Wisor, JP Edgar, DM Yesavage, J Ryan, HS McCormick, CM Lapustea, N Murphy, GM TI Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: A role for cholinergic transmission SO NEUROSCIENCE LA English DT Article DE sleep deprivation; beta amyloid immunization; Tg2576; electroencephalogram; donepezil; amyloid precursor protein ID AMYLOID PRECURSOR PROTEIN; GENE-TARGETED MICE; A-BETA; BASAL FOREBRAIN; SUPRACHIASMATIC NUCLEUS; MEMORY DEFICITS; SENILE-DEMENTIA; CHOLINESTERASE-INHIBITORS; PLAQUE PATHOLOGY; APOLIPOPROTEIN-E AB The Tg2576 mouse model of Alzheimer's disease (AD) exhibits age-dependent amyloid P (AP) deposition in the brain. We studied electroencephalographically defined sleep and the circadian regulation of waking activities in Tg2576 mice to determine whether these animals exhibit sleep abnormalities akin to those in AD. In Tg2576 mice at all ages studied, the circadian period of wheel running rhythms in constant darkness was significantly longer than that of wild type mice. In addition, the increase in electroencephalographic delta (1-4 Hz) power that occurs during non-rapid eye movement sleep after sleep deprivation was blunted in Tg2576 mice relative to controls at all ages studied. Electroencephalographic power during non-rapid eye movement sleep was shifted to higher frequencies in plaque-bearing mice relative to controls. The wake-promoting efficacy of the acetylcholinesterase inhibitor donepezil was lower in plaquebearing Tg2576 mice than in controls. Sleep abnormalities in Tg2576 mice may be due in part to a cholinergic deficit in these mice. At 22 months of age, two additional deficits emerged in female Tg2576 mice: time of day-dependent modulation of sleep was blunted relative to controls and rapid eye movement sleep as a percentage of time was lower in Tg2576 than in wild type controls. The rapid eye movement sleep deficit in 22 month-old female Tg2576 mice was abolished by brief passive immunization with an N-terminal antibody to Abeta. The Tg2576 model provides a uniquely powerful tool for studies on the pathophysiology of and treatments for sleep deficits and associated cholinergic abnormalities in AD. (C) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Neurosci Res Labs, Stanford, CA 94305 USA. VA Palo Alto Heather Care Syst, Natl Inst Aging Alzheimers Dis Core Ctr, Palo Alto, CA USA. Palo Alto VA Hlth Care Syst, Dept Vet Affairs, Sierra Pacific Mental Illness Res Educ & Clin Ct, Palo Alto, CA USA. RP Murphy, GM (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Neurosci Res Labs, Med Sch Lab Surge Bldg Room P-104, Stanford, CA 94305 USA. EM gmurphy@leland.stanford.edu FU NIA NIH HHS [AG 17824]; NIMH NIH HHS [MH 40041] NR 75 TC 73 Z9 74 U1 4 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 131 IS 2 BP 375 EP 385 DI 10.1016/j.neuroscience.2004.11.018 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 901BQ UT WOS:000227258400011 PM 15708480 ER PT J AU Mamczarz, J Bowker, JL Duffy, K Zhu, M Hagepanos, A Ingram, DK AF Mamczarz, J Bowker, JL Duffy, K Zhu, M Hagepanos, A Ingram, DK TI Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxy-D-glucose treatment SO NEUROSCIENCE LA English DT Article DE food; fasting; hunger; stress; glycolysis; insulin ID STRESS-INDUCED SENSITIZATION; CHRONIC FOOD RESTRICTION; INDUCED CORTICOSTERONE SECRETION; LIFE-SPAN; DOPAMINE TRANSPORTER; CALORIE RESTRICTION; VOLUNTARY EXERCISE; NERVOUS-SYSTEM; DIABETIC-RATS; BODY-WEIGHT AB Diet restriction (DR) in rodents increases lifespan, reduces age-related disease and pathology, increases stress responses, and maintains better function later into life compared with conventional ad libitum (AL) feeding. We have been investigating different DR regimens and also DR mimetics that stimulate stress response pathways that are activated by DR. By inhibiting glycolysis, feeding or injection of 2-deoxy-D-glucose (2DG) has been proposed as a DR mimetic and has been shown to provide neuroprotection. In the current study, we examined whether 2DG treatment produces behavioral changes similar to those observed in DR rats following stimulation of the dopaminergic (DA) system by D-amphetamine (AMPH). Male Fischer 344 rats were maintained on different dietary regimens: 40% daily DR (40% DR); every-other-day feeding (EOD); or AL with some groups provided food containing 0.4% 2DG or injected i.p. with 2DG. In addition, we examined the persistence of effects of DR or 2DG feeding after switching rats to AL. When locomotor activity was assessed at different time points following initiation of dietary treatments, we noted that the enhancement of AMPH-induced locomotor responses emerged earlier in DR rats than observed in 2DG fed rats, but 40% DR and EOD rats responded in a similar manner. Enhanced locomotor responses persisted in 2DG fed rats even when returned to normal diet for 1 month and in the case of DR rats even after 2 months of AL feeding. Three weeks of 2DG injections also enhanced AMPH response, but this effect was transient. The most important finding was that 2DG did not affect body weight or diet intake yet had effects similar to DR. Thus, 2DG appears to activate DA pathways in the same direction as DR does but without the necessity of reducing caloric intake. (C) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov NR 65 TC 8 Z9 8 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 131 IS 2 BP 451 EP 464 DI 10.1016/j.neuroscience.2004.11.019 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 901BQ UT WOS:000227258400017 PM 15708486 ER PT J AU Simonyan, K Jurgens, U AF Simonyan, K Jurgens, U TI Afferent subcortical connections into the motor cortical larynx area in the rhesus monkey SO NEUROSCIENCE LA English DT Article DE motor cortex; larynx area; vocal fold control; thalamus; phonation; neuroanatomy ID SQUIRREL-MONKEY; PARABRACHIAL NUCLEUS; CEREBRAL-CORTEX; SOLITARY TRACT; PROJECTIONS; ORGANIZATION; THALAMUS; SPEECH; BRAIN; RAT AB In three rhesus monkeys (Macaca mulatta), the inferior motor cortex was explored by electrical stimulation for sites yielding vocal fold adduction. The retrograde tracer wheat germ-agglutinin-conjugated horseradish peroxidase was injected into the effective sites. Within the forebrain, retrogradely labeled cells were found in the claustrum, basal nucleus of Meynert, substantia innominata, extended amygdala, lateral and posterior hypothalamic area, field H of Forel, and a number of thalamic nuclei with the strongest labeling in the nuclei ventralis lateralis, ventralls posteromedialis, including its parvocellular part, medialis dorsalis and centrum medianum, and weaker labeling in the nuclei ventralis anterior, ventralls posterolateral is, intermediodorsalis, paracentrails, parafascicularis and pulvinaris anterior. In the midbrain, labeling was found in the deep mesencephalic nucleus, ventral tegmental area, and substantia nigra. In the lower brainstem, labeled cells were found in the pontine reticular formation, median and dorsal raphe nuclei, medial parabrachial nucleus, and locus coeruleus. The findings are discussed in terms of the possible role of these structures in voluntary vocal control. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 German Primate Ctr, Dept Neurobiol, D-37077 Gottingen, Germany. RP Simonyan, K (reprint author), NINDS, NIH, Laryngeal & Speech Sect, Med Neurol Branch, Bldg 10,Room 5D38, Bethesda, MD 20892 USA. EM simonyak@ninds.nih.gov OI Simonyan, Kristina/0000-0001-7444-0437 NR 55 TC 21 Z9 21 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 130 IS 1 BP 119 EP 131 DI 10.1016/j.neuroscience.2004.06.071 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 879OD UT WOS:000225726200011 PM 15561430 ER PT J AU Simonyan, K Jurgens, U AF Simonyan, K Jurgens, U TI Afferent cortical connections of the motor cortical larynx area in the rhesus monkey SO NEUROSCIENCE LA English DT Article DE motor cortex; larynx representation; vocal fold control; phonation; neuroanatomy ID PRIMARY SOMATOSENSORY CORTEX; MACAQUE MONKEY; INTRACORTICAL MICROSTIMULATION; MULTIPLE REPRESENTATIONS; FUNCTIONAL-PROPERTIES; MACACA-FASCICULARIS; PREFRONTAL CORTEX; SQUIRREL-MONKEYS; CINGULATE CORTEX; PREMOTOR CORTEX AB The present study describes the cortical input into the motor cortical larynx area. The retrograde tracer horseradish peroxidase-conjugated wheat germ agglutinin was injected into the electrophysiologically identified motor cortical larynx area in three rhesus monkeys (Macaca mulatta). Retrogradely labeled cells were found in the surrounding premotor cortex (areas 6V and 6D), primary motor cortex (area 4), primary somatosensory cortex (areas 3, 1 and 2), anterior and posterior secondary somatosensory cortex and the probable homologue of Broca's area (areas 44 and 45); furthermore, labeling was found in the supplementary motor area, anterior and posterior cingulate cortex (areas 24 and 23), prefrontal and orbital frontal cortex (areas 8A, 46V, 47/12L, 47/12O, 13), agranular, dysgranular and granular insula as well as in the cortex within the upper bank of the middle third of the superior temporal sulcus (area TPO). The majority of these regions are reciprocally connected with the motor cortical larynx area (Brain Res 949 (2000) 23]. The laryngeal motor cortical input is discussed in relation to the connections of other motor cortical areas and its role in vocal control. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 German Primate Ctr, Dept Neurobiol, D-37077 Gottingen, Germany. RP Simonyan, K (reprint author), NINDS, NIH, Laryngeal & Speech Sect, Med Neurol Branch, Bldg 10,Room 5D38, Bethesda, MD 20892 USA. EM simonyak@ninds.nih.gov OI Simonyan, Kristina/0000-0001-7444-0437 NR 71 TC 25 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 130 IS 1 BP 133 EP 149 DI 10.1016/j.neuroscience.2004.08.013 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 879OD UT WOS:000225726200012 PM 15561431 ER PT J AU Nomura, M Akama, KT Alves, SE Korach, KS Gustafsson, JA Pfaff, DW Ogawa, S AF Nomura, M Akama, KT Alves, SE Korach, KS Gustafsson, JA Pfaff, DW Ogawa, S TI Differential distribution of estrogen receptor (ER)-alpha and ER-beta in the midbrain raphe nuclei and periaqueductal gray in male mouse: Predominant role of ER-beta in midbrain serotonergic systems SO NEUROSCIENCE LA English DT Article DE serotonin; aggression; tryptophan hydroxylase; sexual behavior; knockout mouse; immunocytochemistry ID MESSENGER-RNA EXPRESSION; OVARIAN-STEROID REGULATION; MASCULINE SEXUAL-BEHAVIOR; CENTRAL-NERVOUS-SYSTEM; AGGRESSIVE-BEHAVIOR; PROGESTIN RECEPTORS; DORSAL RAPHE; MICE LACKING; ALPHA GENE; RHESUS MACAQUES AB We examined the distribution of estrogen receptor (ER)-alpha and ER-beta immunoreactive (ir) cells in the dorsal (DRN) and median/paramedian (MPRN) raphe nuclei in male mice. ER-alpha ir neurons were scattered across the three subdivisions (ventral, dorsal, and lateral) of the DRN and the MPRN. Robust ER-beta ir cells were observed throughout the raphe nuclei, and were particularly abundant in the ventral and dorsal subdivisions of the DRN. Using dual-label immunocytochemistry for ER-alpha or ER-beta with tryptophan hydroxylase (TPH), the rate-limiting enzyme for 5-hydroxytryptamine (5-HT) synthesis, over 90% of ER-beta ir cells exhibited TPH-ir in all DRN subdivisions, whereas only 23% of ER-alpha ir cells contained TPH. Comparisons of ER-alpha knockout (alphaERKO) as well as ER-beta knockout (betaERKO) mice with their respective wild-type (WT) littermates revealed that gene disruption of either ER-alpha or ER-beta did not affect the other ER subtype expression in the raphe nuclei. In situ hybridization histochemistry revealed that there was a small but statistically significant decrease in TPH mRNA expression in the ventral DRN subdivision in PERKO mice compared with betaWT mice, whereas TPH mRNA levels were not affected in alphaERKO mice. These findings support a hypothesis that ER-beta activation may contribute to the estrogenic regulation of neuroendocrine and behavioral functions, in part, by acting directly on 5-HT neurons in the raphe nuclei in male mice. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden. RP Ogawa, S (reprint author), Rockefeller Univ, Neurobiol & Behav Lab, 1230 York Ave,Box 275, New York, NY 10021 USA. EM ogawa@mail.rockefeller.edu OI Korach, Kenneth/0000-0002-7765-418X NR 57 TC 43 Z9 48 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 130 IS 2 BP 445 EP 456 DI 10.1016/j.neuroscience.2004.09.028 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 884JG UT WOS:000226080300017 PM 15664701 ER PT J AU Tao-Cheng, JH Vinade, L Winters, CA Reese, TS Dosemeci, A AF Tao-Cheng, JH Vinade, L Winters, CA Reese, TS Dosemeci, A TI Inhibition of phosphatase activity facilitates the formation and maintenance of NMDA-induced calcium/calmodulin-dependent protein kinase II clusters in hippocampal neurons SO NEUROSCIENCE LA English DT Article DE immunogold electron microscopy; calyculin A; okadaic acid; calcium/calmodulin-dependent protein kinase II; autophosphorylation ID POSTSYNAPTIC DENSITY; CA-2+-INDEPENDENT ACTIVITY; SELF-ASSOCIATION; OKADAIC ACID; AUTOPHOSPHORYLATION; CELLS; FORM; GENERATION; MECHANISM; SUBUNIT AB The majority of hippocampal neurons in dissociated cultures and in intact brain exhibit clustering of calcium/ calmodulin-dependent protein kinase II (CaMKII) into spherical structures with an average diameter of 110 nm when subjected to conditions that mimic ischemia and excitotoxicity [Neuroscience 106 (2001) 69]. Because clustering of CaMKII would reduce its effective concentration within the neuron, it may represent a cellular strategy to prevent excessive CaMKII-mediated phosphorylation during episodes of Ca2+ overload. Here we employ a relatively mild excitatory stimulus to promote sub-maximal clustering for the purpose of studying the conditions for the formation and disappearance of CaMKII clusters. Treatment with 30 muM N-methyl-D-aspartic acid (NMDA) for 2 min produced CaMKII clustering in approximately 15% of dissociated hippocampal neurons in culture, as observed by pre-embedding immunogold electron microscopy. These CaMKII clusters could be labeled with antibodies specific to the phospho form (Thr286) of CaMKII, suggesting that at least some of the CaMKII molecules in clusters are autophosphorylated. To test whether phosphorylation is involved in the formation and maintenance of CaMKII clusters, the phosphatase inhibitors calyculin A (5 nM) or okadaic acid (1 muM) were included in the incubation medium. With inhibitors more neurons exhibited CaMKII clusters in response to 2 min NMDA treatment. Furthermore, 5 min after the removal of NMDA and Ca2+, CaMKII clusters remained and could still be labeled with the phospho-specific antibody. In contrast, in the absence of phosphatase inhibitors, no clusters were detected 5 min after the removal of NMDA and Ca2+ from the medium. These results suggest that phosphatases type 1 and/or 2A regulate the formation and disappearance of CaMKII clusters. (C) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NINDS, Electron Microscopy Facil, NIH, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Program Mol Biol, Marine Biol Lab, Woods Hole, MA 02543 USA. RP NINDS, Electron Microscopy Facil, NIH, Bldg 36,Room 2A21, Bethesda, MD 20892 USA. EM chengs@ninds.nih.gov NR 23 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 130 IS 3 BP 651 EP 656 DI 10.1016/j.neuroscience.2004.10.008 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 885UE UT WOS:000226181700010 PM 15590149 ER PT J AU Holmes, A le Guisquet, AM Vogel, E Millstein, RA Leman, S Belzung, C AF Holmes, A le Guisquet, AM Vogel, E Millstein, RA Leman, S Belzung, C TI Early life genetic, epigenetic and environmental factors shaping emotionality in rodents SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Article; Proceedings Paper CT Satellite Symposium on Defensive Behavior CY JUN, 2004 CL Key West, FL DE stress; anxiety; depression; development; mouse; strain; gene; early life; cross-fostering; enrichment ID NEONATAL MATERNAL SEPARATION; ANXIETY-LIKE BEHAVIOR; CORTICOTROPIN-RELEASING-FACTOR; CHILDHOOD SEXUAL-ABUSE; PITUITARY-ADRENAL AXIS; POSTTRAUMATIC-STRESS-DISORDER; RECEPTOR SUBUNIT EXPRESSION; MALE WISTAR RATS; LONG-EVANS RATS; ADULT-RATS AB Childhood trauma is known to increase risk for emotional disorder, and addiction. However, little is currently understood about the neurodevelopmental basis of these effects, or how genetic and epigenetic factors interact with the environment to shape the systems subserving emotionality. In this review, we discuss the use of rodent models of early life emotional experience to study these issues in the laboratory and present some of our pertinent findings. In rats, postnatal maternal separation can produce lasting increases in emotional behavior and stressor-reactivity, together with alterations in various brain neurotransmitter systems implicated in emotionality, including corticotropin-releasing factor, serotonin, norepinephrine, and glutamate. Genetic differences between inbred mouse strains have been exploited to further study how maternal behavior affects emotional development using techniques such as cross-fostering and generation of inter-strain hybrids. Together with our own recent data, the findings of these studies demonstrate the pervasive influence of maternal and social environments during sensitive developmental periods and reveal how genetic factors determine how these early life experiences can shape brain and behavior throughout life. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet, NIH, Rockville, MD 20852 USA. UFR Sci & Tech, F-37200 Tours, France. RP Holmes, A (reprint author), NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet, NIH, 9000 Rockville Pike,Bldg 10,Room 3C216,5625 Fishe, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov; catherine.belzung@univ-tours.fr RI Leman, Samuel/P-6019-2016; Belzung, Catherine/P-6512-2016 OI Leman, Samuel/0000-0002-0999-9979; Belzung, Catherine/0000-0001-6095-5974 NR 183 TC 170 Z9 177 U1 5 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PY 2005 VL 29 IS 8 BP 1335 EP 1346 DI 10.1016/j.neubiorev.2005.04.012 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 982EG UT WOS:000233140100017 PM 16095695 ER PT B AU Bachrach, C King, R Yuan, A AF Bachrach, C King, R Yuan, A BE Booth, A Crouter, AC TI Children as private and public goods: Implications of fertility trends SO New Population Problem: Why Families in Developed Countries are Shrinking and What it Means SE PENN STATE UNIVERSITY FAMILY ISSUES SYMPOSIA SERIES LA English DT Proceedings Paper CT National Symposium on Creating the Next Generation - Social, Economic and Psychological Processes Underlying Fertility in Developed Countries CY OCT 09-10, 2003 CL Penn State Univ, University Pk, PA HO Penn State Univ ID ECONOMIC-GROWTH; CHILDBEARING; IMMIGRATION; TRANSITION; ATTITUDES; SECURITY; PARENTS; MIDLIFE; DECLINE; ADULTS C1 NICHHD, Bethesda, MD USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-4978-5 J9 PENN STATE UNIV FAM PY 2005 BP 183 EP 197 PG 15 WC Demography SC Demography GA BCF02 UT WOS:000228994500013 ER PT B AU Tweedie, D Giordano, T Yu, S Luo, W Holloway, HW Pyle, RS Brossi, A Sambamurti, K Lahiri, DK Greig, NH AF Tweedie, D Giordano, T Yu, S Luo, W Holloway, HW Pyle, RS Brossi, A Sambamurti, K Lahiri, DK Greig, NH BE Fisher, A Hanin, I Memo, M Stocchi, F TI TNF-alpha synthesis inhibitors on the 3-phthalimidoglutarimide backbone as therapeutic candidates for neurodegenerative diseases SO New Trends in Alzheimer and Parkinson Related Disorders: ADPD 2005 LA English DT Proceedings Paper CT 7th International Conference on Progress in Alzheimers and Parkinsons Disease CY MAR 09-13, 2005 CL Sorrento, ITALY ID NECROSIS-FACTOR-ALPHA; AMYLOID PRECURSOR PROTEIN; MESSENGER-RNA DEGRADATION; CENTRAL-NERVOUS-SYSTEM; UA-RICH SEQUENCES; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; BRAIN-INJURY; 5'-UNTRANSLATED REGION; RESPONSIVE ELEMENT AB An over-expression of cytokines, particularly of tumor necrosis factor-alpha (TNF-alpha), is a major facet of inflammation and invariably accompanies neurodegenerative diseases, exemplified by Parkinson's disease (PD), Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), besides a variety of prevalent non-neurological disorders, represented by rheumatoid arthritis. TNF-alpha has been validated as a worthwhile drug target with the approval of the therapeutics Enbrel (Etanercept) and Remicade (Infliximab) for the treatment of adult and juvenile rheumatoid arthritis, and other disorders associated with inappropriate inflammatory responses. As injected proteins, however, these agents minimally pass through biological barriers, and thus have restricted brain penetrability to negate their potential utility in neurodegenerative diseases. In our continuing effort to design and develop neurological agents of potential clinical value, we focused our drug design on the pharmacophore of 3-phthalimidoglutarimide (thalidomide) as it enhances the degradation of TNF-alpha mRNA and, thereby, lowers TNF-alpha synthesis and secretion(1). Novel, lipophilic thiothalidomide analogues were synthesized and evaluated for their ability to lower secreted TNF-alpha levels in human peripheral blood mononuclear cells (PBMCs) in cell cultures stimulated with lipopolysacharide (LPS). Specific compounds effectively inhibited TNF-alpha secretion more potently than thalidomide via a post-transcriptional mechanism that decreased TNF-alpha mRNA stability and are under evaluation in animal models. C1 NIA, NIH, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Tweedie, D (reprint author), NIA, NIH, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NR 59 TC 0 Z9 0 U1 2 U2 2 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-7587-174-4 PY 2005 BP 77 EP 86 PG 10 WC Biochemistry & Molecular Biology; Clinical Neurology SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BED80 UT WOS:000236896400015 ER PT S AU Hofseth, LJ Robles, AI Espey, MG Harris, CC AF Hofseth, LJ Robles, AI Espey, MG Harris, CC BE Packer, L Cadenas, E TI Nitric oxide is a signaling molecule that regulates gene expression SO NITRIC OXIDE, PT E SE Methods in Enzymology LA English DT Review; Book Chapter ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; HEME OXYGENASE-1; IN-VIVO; NITROSATIVE STRESS; OXIDATIVE STRESS; HUMAN-CELLS; MICROARRAY ANALYSIS; ENDOTHELIAL-CELLS; S-NITROSYLATION; CYCLIC-GMP AB Nitric oxide (NO) is a dynamic and bioreactive molecule that can both participate in and inhibit the genesis of disease. Its ability to have an impact on a wide range of physiological events stems from its capacity to reversibly alter the expression of specific genes and the activities of a wide range of proteins and signaling pathways. Yet, NO degrees remains an enigmatic molecule. Recently developed technologies, including gene-chips, two-dimensional electrophoresis, RNA interference, matrix-assisted laser desorption ionization (MALDI)-TOF (time-of-flight) mass spectrometry, and protein arrays will allow us to better understand how NO degrees and associated reactive nitrogen species (RNS) regulate both physiology and disease states, toward the development of treatments using NO(center dot) synthase inhibitors or NO(center dot) 141 donors. C1 Univ S Carolina, Coll Pharm, Columbia, SC 29208 USA. Natl Canc Inst, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Hofseth, LJ (reprint author), Univ S Carolina, Coll Pharm, CLS 109, Columbia, SC 29208 USA. NR 72 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182801-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 396 BP 326 EP 340 DI 10.1016/S0076-6879(05)96027-8 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDN38 UT WOS:000234454400027 PM 16291242 ER PT S AU Kontaxis, G Delaglio, F Bax, A AF Kontaxis, G Delaglio, F Bax, A BE James, TL TI Molecular fragment replacement approach to protein structure determination by chemical shift and dipolar homology database mining SO NUCLEAR MAGNETIC RESONANCE OF BIOLOGICAL MACROMOLECULES, PART C SE Methods in Enzymology LA English DT Review; Book Chapter ID LIQUID-CRYSTALLINE MEDIUM; NUCLEAR MAGNETIC-RESONANCE; ACANTHAMOEBA PROFILIN-I; DE-NOVO DETERMINATION; HIGH-RESOLUTION NMR; X-RAY STRUCTURES; INDUCED ALIGNMENT; BIOLOGICAL MACROMOLECULES; ORIENTED MACROMOLECULES; DISTANCE RESTRAINTS AB A novel approach is described for determining backbone structures of proteins that is based on finding fragments in the protein data bank (PDB). For each fragment in the target protein, usually chosen to be 7-10 residues in length, PDB fragments are selected that best fit to experimentally determined one-bond heteronuclear dipolar couplings and that show agreement between chemical shifts predicted for the PDB fragment and experimental values for the target fragment. These fragments are subsequently refined by simulated annealing to improve agreement with the experimental data. If the lowest-energy refined fragments form a unique structural cluster, this structure is accepted and side chains are added on the basis of a conformational database potential. The sequential backbone assembly process extends the chain by translating an accepted fragment onto it. For several small proteins, with extensive sets of dipolar couplings measured in two alignment media, a unique final structure is obtained that agrees well with structures previously solved by conventional methods. With less dipolar input data, large, oriented fragments of each protein are obtained, but their relative positioning requires either a small set of translationally restraining nuclear Overhauser enhancements (NOES) or a protocol that optimizes burial of hydrophobic groups and pairing of beta-strands. C1 Univ Vienna, Dept Theoret Chem & Mol Struct Biol, A-1030 Vienna, Austria. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Kontaxis, G (reprint author), Univ Vienna, Dept Theoret Chem & Mol Struct Biol, Waehringer Guertel 18, A-1030 Vienna, Austria. NR 79 TC 43 Z9 45 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182799-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 394 BP 42 EP + PG 42 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCD19 UT WOS:000228718700003 PM 15808217 ER PT S AU Grishaev, A Llinas, M AF Grishaev, A Llinas, M BE James, TL TI Protein structure elucidation from minimal NMR data: The CLOUDS approach SO NUCLEAR MAGNETIC RESONANCE OF BIOLOGICAL MACROMOLECULES, PART C SE Methods in Enzymology LA English DT Review; Book Chapter ID AMBIGUOUS DISTANCE RESTRAINTS; RELAXATION MATRIX APPROACH; AUTOMATED ASSIGNMENT; HIGH-RESOLUTION; NOESY SPECTRA; RESONANCE ASSIGNMENT; MULTIDIMENSIONAL NMR; OPTIMIZATION METHODS; BAYESIAN PROTOCOL; DIPOLAR COUPLINGS AB In this chapter we review automated methods of protein NMR data analysis and expand on the assignment-independent CLOUDS approach. As presented, given a set of reliable NOEs it is feasible to derive a spatial H-atom distribution that provides a low-resolution image of the protein structure. In order to generate such a list of unambiguous NOEs, a probabilistic assessment of the NOE identities (in terms of frequency-labeled H-atom sources) was developed on the basis of Bayesian inference. The methodology, encompassing programs SPI and BACUS, provides a list of "clean" NOES that does not hinge on prior knowledge of sequence-specific resonance assignments or a preliminary structural model. As such, the combined SPI/BACUS approach, intrinsically adaptable to include 13C- and/or 15N-edited experiments, affords a useful tool for the analysis of NMR data irrespective of whether the adopted structure calculation protocol is assignment-dependent. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. RP Grishaev, A (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL29409]; NIGMS NIH HHS [GM67964] NR 77 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182799-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 394 BP 261 EP 295 PG 35 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCD19 UT WOS:000228718700010 PM 15808224 ER PT J AU Bibillo, A Lener, D Klarmann, GJ Le Grice, SFJ AF Bibillo, A Lener, D Klarmann, GJ Le Grice, SFJ TI Functional roles of carboxylate residues comprising the DNA polymerase active site triad of Ty3 reverse transcriptase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TEMPLATE-PRIMER UTILIZATION; RIBONUCLEASE-H DOMAIN; RNASE-H; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; MUTATIONAL ANALYSIS; FOOTPRINT ANALYSIS; TYPE-1 AB Aspartic acid residues comprising the -D-(aa) (n) -Y-L-D-D- DNA polymerase active site triad of reverse transcriptase from the Saccharomyces cerevisiae long terminal repeat-retrotransposon Ty3 (Asp151, Asp213 and Asp214) were evaluated via site-directed mutagenesis. An Asp151-->Glu substitution showed a dramatic decrease in catalytic efficiency and a severe translocation defect following initiation of DNA synthesis. In contrast, enzymes harboring the equivalent alteration at Asp213 and Asp214 retained DNA polymerase activity. Asp151-->Asn and Asp213-->Asn substitutions eliminated both polymerase activities. However, while Asp214 of the triad could be replaced by either Asn or Glu, introducing Gln seriously affected processivity. Mutants of the carboxylate triad at positions 151 and 213 also failed to catalyze pyrophosphorolysis. Finally, alterations to the DNA polymerase active site affected RNase H activity, suggesting a close spatial relationship between these N- and C-terminal catalytic centers. Taken together, our data reveal a critical role for Asp151 and Asp213 in catalysis. In contrast, the second carboxylate of the Y-L-D-D motif (Asp214) is not essential for catalysis, and possibly fulfills a structural role. Although Asp214 was most insensitive to substitution with respect to activity of the recombinant enzyme, all alterations at this position were lethal for Ty3 transposition. C1 NCI, Resistance Mech Lab, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Le Grice, SFJ (reprint author), NCI, Resistance Mech Lab, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM slegrice@ncifcrf.gov NR 60 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 1 BP 171 EP 181 DI 10.1093/nar/gki150 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 889XU UT WOS:000226477000016 PM 15647500 ER PT J AU Kawano, M Reynolds, AA Miranda-Rios, J Storz, G AF Kawano, M Reynolds, AA Miranda-Rios, J Storz, G TI Detection of 5'- and 3'-UTR-derived small RNAs and cis-encoded antisense RNAs in Escherichia coli SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPARATIVE GENOMICS; LYSINE BIOSYNTHESIS; GENE-EXPRESSION; NONCODING RNAS; BACTERIA; TRANSCRIPTION; IDENTIFICATION; OPERON; TRANSLATION; MECHANISMS AB Evidence is accumulating that small, noncoding RNAs are important regulatory molecules. Computational and experimental searches have led to the identification of similar to60 small RNA genes in Escherichia coli. However, most of these studies focused on the intergenic regions and assumed that small RNAs were >50 nt. Thus, the previous screens missed small RNAs encoded on the antisense strand of protein-coding genes and small RNAs of <50 nt. To identify additional small RNAs, we carried out a cloning-based screen focused on RNAs of 30-65 nt. In this screen, we identified RNA species corresponding to fragments of rRNAs, tRNAs and known small RNAs. Several of the small RNAs also corresponded to 5'- and 3'-untranslated regions (UTRs) and internal fragments of mRNAs. Four of the 3'-UTR-derived RNAs were highly abundant and two showed expression patterns that differed from the corresponding mRNAs, suggesting independent functions for the 3'-UTR-derived small RNAs. We also detected three previously unidentified RNAs encoded in intergenic regions and RNAs from the long direct repeat and hok/sok elements. In addition, we identified a few small RNAs that are expressed opposite protein-coding genes and could base pair with 5' or 3' ends of the mRNAs with perfect complementarity. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Natl Autonomous Univ Mexico, Inst Biotechnol, Dept Mol Microbiol, Cuernavaca 62210, Morelos, Mexico. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM storz@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 NR 39 TC 129 Z9 140 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 3 BP 1040 EP 1050 DI 10.1093/nar/gki256 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903EC UT WOS:000227407300034 PM 15718303 ER PT J AU Dyer, KD Rosenberg, HF AF Dyer, KD Rosenberg, HF TI The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue-specific expression SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EOSINOPHIL-DERIVED NEUROTOXIN; RIBONUCLEASE-A SUPERFAMILY; MOLECULAR-CLONING; INTRONIC ENHANCER; CATIONIC PROTEIN; CHROMOSOMAL LOCALIZATION; RNS2 GENE; CD94 GENE; IDENTIFICATION; LIVER AB The ribonuclease A (RNase A) superfamily has been the subject of extensive studies in the areas of protein evolution, structure and biochemistry and are exciting molecules in that they appear to be responding to unique selection pressures, generating proteins capable of multiple and diverse activities. The RNase 4 and RNase 5/ang 1 shared locus breaks a pattern that is otherwise canonical among the members of the RNase A gene superfamily. Conserved among humans, mice and rats, the locus includes two non-coding exons followed by two distinct exons encoding RNase 4 and RNase 5/ang 1. Transcription from this locus is controlled by differential splicing and tissue-specific expression from promoters located 5' to each of the non-coding exons. Promoter 1, 5' to exon I, is universally active, while Promoter 2, 5' to exon II, is active only in hepatic cells in promoter assays in vitro. Transcription from Promoter 2 is dependent on an intact HNF-1 consensus binding site which binds the transcription factor HNF-1alpha. In summary, RNase 4 and RNase 5/ang 1 are unique among the RNase A ribonuclease genes in that they maintain a complex gene locus that is conserved across species with transcription initiated from tissue-specific dual promoters followed by differential exon splicing. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Dyer, KD (reprint author), 10 Ctr Dr MSC 1886,Bldg 10 Room 11C216, Bethesda, MD 20892 USA. EM kdyer@niaid.nih.gov NR 41 TC 10 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 3 BP 1077 EP 1086 DI 10.1093/nar/gki250 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903EC UT WOS:000227407300038 PM 15722482 ER PT J AU Sukhanova, MV Khodyreva, SN Lebedeva, NA Prasad, R Wilson, SH Lavrik, OI AF Sukhanova, MV Khodyreva, SN Lebedeva, NA Prasad, R Wilson, SH Lavrik, OI TI Human base excision repair enzymes apurinic/apyrimidinic endonuclease1 (APE1), DNA polymerase beta and poly(ADP-ribose) polymerase 1: interplay between strand-displacement DNA synthesis and proofreading exonuclease activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN APURINIC ENDONUCLEASE; MAMMALIAN-CELLS; DOWN-REGULATION; BOVINE TESTIS; LIGASE-III; DAMAGE; XRCC1; REQUIREMENT; PATHWAY; RECONSTITUTION AB We examined interactions between base excision repair (BER) DNA intermediates and purified human BER enzymes, DNA polymerase beta (pol beta), apurinic/apyrimidinic endonuclease (APE1) and poly( ADPribose) polymerase-1 (PARP-1). Studies under steady-state conditions with purified BER enzymes and BER substrates have already demonstrated interplay between these BER enzymes that is sensitive to the respective concentrations of each enzyme. Therefore, in this study, using conditions of enzyme excess over substrate DNA, we further examine the question of interplay between BER enzymes on BER intermediates. The results reveal several important differences compared with data obtained using steady-state assays. Excess PARP-1 antagonizes the action of pol beta, producing a complete block of long patch BER strand-displacement DNA synthesis. Surprisingly, an excess of APE1 stimulates strand-displacement DNA synthesis by pol beta, but this effect is blocked by PARP-1. The APE1 exonuclease function appears to be modulated by the other BER proteins. Excess APE1 over pol beta may allow APE1 to perform both exonuclease function and stimulation of strand-displacement DNA synthesis by pol beta. This enables pol b to mediate long patch sub-pathway. These results indicate that differences in the stoichiometry of BER enzymes may regulate BER. C1 Russian Acad Sci, Novosibirsk Inst Chem Biol & Fundamental Med, Siberian Div, Novosibirsk 630090, Russia. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Lavrik, OI (reprint author), Russian Acad Sci, Novosibirsk Inst Chem Biol & Fundamental Med, Siberian Div, Prospect Lavrentieva 8, Novosibirsk 630090, Russia. EM lavrik@niboch.nsc.ru RI Lebedeva, Natalya /G-4758-2013; Khodyreva, Svetlana/G-4659-2013; Sukhanova, Maria/G-5539-2013; Lavrik, Olga /G-4641-2013 NR 50 TC 75 Z9 84 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 4 BP 1222 EP 1229 DI 10.1093/nar/gki266 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905JW UT WOS:000227565400021 PM 15731342 ER PT J AU Opresko, PL Fan, JH Danzy, S Wilson, DM Bohr, VA AF Opresko, PL Fan, JH Danzy, S Wilson, DM Bohr, VA TI Oxidative damage in telomeric DNA disrupts recognition by TRF1 and TRF2 SO NUCLEIC ACIDS RESEARCH LA English DT Article DE Cuticle; cracking; epidermis; fruit growth; Lycopersicon esculentum; plant biomechanics; ripening; stiffening; tomato ID MAMMALIAN TELOMERES; IONIZING-RADIATION; HUMAN FIBROBLASTS; MAJOR HUMAN; STRESS; REPAIR; INSTABILITY; ATTRITION; LENGTH; SITE AB The ends of linear chromosomes are capped by protein-DNA complexes termed telomeres. Telomere repeat binding factors 1 and 2 (TRF1 and TRF2) bind specifically to duplex telomeric DNA and are critical components of functional telomeres. Consequences of telomere dysfunction include genomic instability, cellular apoptosis or senescence and organismal aging. Mild oxidative stress induces increased erosion and loss of telomeric DNA in human fibroblasts. We performed binding assays to determine whether oxidative DNA damage in telomeric DNA alters the binding activity of TRF1 and TRF2 proteins. Here, we report that a single 8-oxo-guanine lesion in a defined telomeric substrate reduced the percentage of bound TRF1 and TRF2 proteins by at least 50%, compared with undamaged telomeric DNA. More dramatic effects on TRF1 and TRF2 binding were observed with multiple 8-oxo-guanine lesions in the tandem telomeric repeats. Binding was likewise disrupted when certain intermediates of base excision repair were present within the telomeric tract, namely abasic sites or single nucleotide gaps. These studies indicate that oxidative DNA damage may exert deleterious effects on telomeres by disrupting the association of telomere-maintenance proteins TRF1 and TRF2. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Georgia Inst Technol, Dept Mol Cell Biol, Atlanta, GA 30332 USA. RP Opresko, PL (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Opresko, Patricia/0000-0002-6470-2189 NR 40 TC 107 Z9 111 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 4 BP 1230 EP 1239 DI 10.1093/nar/gki273 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905JW UT WOS:000227565400022 PM 15731343 ER PT J AU Budihas, SR Gorshkova, I Gaidamakov, S Wamiru, A Bona, MK Parniak, MA Crouch, RJ McMahon, JB Beutler, JA Le Grice, SFJ AF Budihas, SR Gorshkova, I Gaidamakov, S Wamiru, A Bona, MK Parniak, MA Crouch, RJ McMahon, JB Beutler, JA Le Grice, SFJ TI Selective inhibition of HIV-1 reverse transcriptase-associated ribonuclease H activity by hydroxylated tropolones SO NUCLEIC ACIDS RESEARCH LA English DT Article DE Cuticle; cracking; epidermis; fruit growth; Lycopersicon esculentum; plant biomechanics; ripening; stiffening; tomato ID STRAND TRANSFER-REACTIONS; BIOLOGICAL-ACTIVITY; RNASE-H; CLEAVAGE; DOMAIN; ACID; HINOKITIOL; TRACT; SITES AB High-throughput screening of a National Cancer Institute library of pure natural products identified the hydroxylated tropolone derivatives beta-thujaplicinol (2,7-dihydroxy-4-1(methylethyl)-2,4,6-cycloheptatrien-1-one) and manicol (1,2,3,4-tetrahydro-5-7-dihydroxy-9-methyl-2-(1-methylethenyl)-6H- benzocyclohepten-6- one) as potent and selective inhibitors of the ribonuclease H ( RNase H) activity of human immunodeficiency virus-type 1 reverse transcriptase (HIV-1 RT). beta-Thujaplicinol inhibited HIV-1 RNase H in vitro with an IC50 of 0.2 mu M, while the IC50 for Escherichia coli and human RNases H was 50 mu M and 5.7 mu M, respectively. In contrast, the related tropolone analog beta-thujaplicin (2-hydroxy-4-(methylethyl)-2,4,6-cycloheptatrien-1-one), which lacks the 7-OH group of the heptatriene ring, was inactive, while manicol, which possesses a 7-OH group, inhibited HIV-1 and E. coli RNases H with IC50 = 1.5 mu M and 40 mu M, respectively. Such a result highlights the importance of the 2,7-dihydroxy function of these tropolone analogs, possibly through a role in metal chelation at the RNase H active site. Inhibition of HIV-2 RT-associated RNase H indirectly indicates that these compounds do not occupy the nonnucleoside inhibitor-binding pocket in the vicinity of the DNA polymerase domain. Both beta-thujaplicinol and manicol failed to inhibit DNA dependent DNA polymerase activity of HIV-1 RT at a concentration of 50 mu M, suggesting that they are specific for the C-terminal RNase H domain, while surface plasmon resonance studies indicated that the inhibition was not due to intercalation of the analog into the nucleic acid substrate. Finally, we have demonstrated synergy between beta-thujaplicinol and calanolide A, a nonnucleoside inhibitor of HIV-1 RT, raising the possibility that both enzymatic activities of HIV-1 RT can be simultaneously targeted. C1 NCI, HIV Drug Resistance Program, Resistance Mech Lab, Ft Detrick, MD 21702 USA. NIH, Div Bioengn & Phys Sci, Prot Biophys Resource, Bethesda, MD 20892 USA. NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. NCI, Mol Targets Dev Program, Ft Detrick, MD 21702 USA. SAIC, Ft Detrick, MD 21702 USA. Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA 15213 USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Resistance Mech Lab, Ft Detrick, MD 21702 USA. EM slegrice@ncifcrf.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 41 TC 113 Z9 124 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 4 BP 1249 EP 1256 DI 10.1093/nar/gki268 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905JW UT WOS:000227565400024 PM 15741178 ER PT J AU Sverdlov, AV Rogozin, IB Babenko, VN Koonin, EV AF Sverdlov, AV Rogozin, IB Babenko, VN Koonin, EV TI Conservation versus parallel gains in intron evolution SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTO-SPLICE SITES; GENES; POSITIONS; EXON; SEQUENCES; INSERTION; ORIGINS AB Orthologous genes from distant eukaryotic species, e.g. animals and plants, share up to 25-30% intron positions. However, the relative contributions of evolutionary conservation and parallel gain of new introns into this pattern remain unknown. Here, the extent of independent insertion of introns in the same sites (parallel gain) in orthologous genes from phylogenetically distant eukaryotes is assessed within the framework of the protosplice site model. It is shown that protosplice sites are no more conserved during evolution of eukaryotic gene sequences than random sites. Simulation of intron insertion into protosplice sites with the observed protosplice site frequencies and intron densities shows that parallel gain can account but for a small fraction (5-10%) of shared intron positions in distantly related species. Thus, the presence of numerous introns in the same positions in orthologous genes from distant eukaryotes, such as animals, fungi and plants, appears to reflect mostly bona fide evolutionary conservation. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Babenko, Vladimir/K-5609-2014; OI Babenko, Vladimir/0000-0002-3077-9559 NR 33 TC 69 Z9 71 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 6 BP 1741 EP 1748 DI 10.1093/nar/gki316 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916PR UT WOS:000228398400014 PM 15788746 ER PT J AU Nakahata, S Kawamoto, S AF Nakahata, S Kawamoto, S TI Tissue-dependent isoforms of mammalian Fox-1 homologs are associated with tissue-specific splicing activities SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PRE-MESSENGER-RNA; TRACT-BINDING-PROTEIN; HEAVY CHAIN-B; VERTEBRATE NONMUSCLE MYOSIN; NERVOUS-SYSTEM; EXON DEFINITION; ELEMENTS; ENHANCER; CLONING; IDENTIFICATION AB An intronic hexanucleotide UGCAUG has been shown to play a critical role in the regulation of tissue-specific alternative splicing of pre-mRNAs in a wide range of tissues. Vertebrate Fox-1 has been shown to bind to this element, in a highly sequence-specific manner, through its RNA recognition motif (RRM). In mammals, there are at least two Fox-1-related genes, ataxin-2 binding protein 1 (A2BP1)/Fox-1 and Fxh/Rbm9, which encode an identical RRM. Here, we demonstrate that both mouse Fxh and A2BP1 transcripts undergo tissue-specific alternative splicing, generating protein isoforms specific to brain and muscle. These tissue-specific isoforms are characterized for their abilities to regulate neural cell-specific alternative splicing of a cassette exon, N30, in the non-muscle myosin heavy chain II-B pre-mRNA, previously shown to be regulated through an intronic distal downstream enhancer (IDDE). All Fxh and A2BP1 isoforms with the RRM are capable of binding to the IDDE in vitro through the UGCAUG elements. Each isoform, however, shows quantitative differences in splicing activity and nuclear distribution in transfected cells. All Fxh isoforms and a brain isoform of A2BP1 show a predominant nuclear localization. Brain isoforms of both Fxh and A2BP1 promote N30 splicing much more efficiently than do the muscle-specific isoforms. Skeletal muscles express additional isoforms that lack a part of the RRM. These isoforms are incapable of activating neural cell-specific splicing and, moreover, can inhibit UGCAUG-dependent N30 splicing. These findings suggest that tissue-specific isoforms of Fxh and A2BP1 play an important role in determining tissue specificity of UGCAUG-mediated alternative splicing. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kawamoto, S (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N202,10 Ctr Dr MSC 1762, Bethesda, MD 20892 USA. EM KawamotS@MAIL.NIH.GOV NR 44 TC 106 Z9 108 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 7 BP 2078 EP 2089 DI 10.1093/nar/gki338 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 921QE UT WOS:000228778700006 PM 15824060 ER PT J AU Gaidamakov, SA Gorshkova, II Schuck, P Steinbach, PJ Yamada, H Crouch, RJ Cerritelli, SM AF Gaidamakov, SA Gorshkova, II Schuck, P Steinbach, PJ Yamada, H Crouch, RJ Cerritelli, SM TI Eukaryotic RNases H1 act processively by interactions through the duplex RNA-binding domain SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; COLI RIBONUCLEASE HI; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; HETERODUPLEX SUBSTRATE; CRITHIDIA-FASCICULATA; CRYSTAL-STRUCTURE; DNA-REPLICATION; SWITCH REGIONS; H1 AB Ribonucleases H have mostly been implicated in eliminating short RNA primers used for initiation of lagging strand DNA synthesis. Escherichia coli RNase HI cleaves these RNA-DNA hybrids in a distributive manner. We report here that eukaryotic RNases H1 have evolved to be processive enzymes by attaching a duplex RNA-binding domain to the RNase H region. Highly conserved amino acids of the duplex RNA-binding domain are required for processivity and nucleic acid binding, which leads to dimerization of the protein. The need for a processive enzyme underscores the importance in eukaryotic cells of processing long hybrids, most of which remain to be identified. However, long RNA-DNA hybrids formed during immunoglobulin class-switch recombination are potential targets for RNase H1 in the nucleus. In mitochondria, where RNase H1 is essential for DNA formation during embryogenesis, long hybrids may be involved in DNA replication. C1 NICHHD, Genet Mol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Off Director,US Dept HHS, Bethesda, MD 20892 USA. NIH, Ctr Mol Modeling, Ctr Informat Technol, US Dept HHS, Bethesda, MD 20892 USA. RP Crouch, RJ (reprint author), NICHHD, Genet Mol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM robert_crouch@nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 40 TC 27 Z9 27 U1 4 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 7 BP 2166 EP 2175 DI 10.1093/nar/gki510 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 921QE UT WOS:000228778700014 PM 15831789 ER PT J AU Nakano, T Katafuchi, A Shimizu, R Terato, H Suzuki, T Tauchi, H Makino, K Skorvaga, M Van Houten, B Ide, H AF Nakano, T Katafuchi, A Shimizu, R Terato, H Suzuki, T Tauchi, H Makino, K Skorvaga, M Van Houten, B Ide, H TI Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress SO NUCLEIC ACIDS RESEARCH LA English DT Article ID URACIL-DNA GLYCOSYLASE; ESCHERICHIA-COLI K-12; NITRIC-OXIDE; NITROUS-ACID; ENDONUCLEASE-V; DEOXYRIBONUCLEIC-ACID; SACCHAROMYCES-CEREVISIAE; SUBSTRATE SPECIFICITIES; XERODERMA PIGMENTOSUM; INDUCED DEAMINATION AB Nitric oxide (NO) induces deamination of guanine, yielding xanthine and oxanine (Oxa). Furthermore, Oxa reacts with polyamines and DNA binding proteins to form cross-link adducts. Thus, it is of interest how these lesions are processed by DNA repair enzymes in view of the genotoxic mechanism of NO. In the present study, we have examined the repair capacity for Oxa and Oxa-spermine cross-link adducts (Oxa-Sp) of enzymes involved in base excision repair (BER) and nucleotide excision repair (NER) to delineate the repair mechanism of nitrosative damage to guanine. Oligonucleotide substrates containing Oxa and Oxa-Sp were incubated with purified BER and NER enzymes or cell-free extracts (CFEs), and the damage-excising or DNA-incising activity was compared with that for control (physiological) substrates. The Oxa-excising activities of Escherichia coli and human DNA glycosylases and HeLa CFEs were 0.2-9% relative to control substrates, implying poor processing of Oxa by BER. In contrast, DNA containing Oxa-Sp was incised efficiently by UvrABC nuclease and SOS-induced E.coli CFEs, suggesting a role of NER in ameliorating genotoxic effects associated with nitrosative stress. Analyses of the activity of CFEs from NER-proficient and NER-deficient human cells on Oxa-Sp DNA confirmed further the involvement of NER in the repair of nitrosative DNA damage. C1 Hiroshima Univ, Grad Sch Sci, Dept Math & Life Sci, Higashihiroshima 7398526, Japan. Shujitsu Univ, Sch Pharm, Dept Biol Pharm, Okayama 7038516, Japan. Ibaraki Univ, Fac Sci, Dept Environm Sci, Mito, Ibaraki 3108512, Japan. Kyoto Univ, Inst Adv Energy, Uji, Kyoto 6110011, Japan. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Ide, H (reprint author), Hiroshima Univ, Grad Sch Sci, Dept Math & Life Sci, Higashihiroshima 7398526, Japan. EM ideh@hiroshima-u.ac.jp NR 67 TC 42 Z9 46 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 7 BP 2181 EP 2191 DI 10.1093/nar/gki513 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 921QE UT WOS:000228778700016 PM 15831791 ER PT J AU Altuvia, Y Landgraf, P Lithwick, G Elefant, N Pfeffer, S Aravin, A Brownstein, MJ Tuschl, T Margalit, H AF Altuvia, Y Landgraf, P Lithwick, G Elefant, N Pfeffer, S Aravin, A Brownstein, MJ Tuschl, T Margalit, H TI Clustering and conservation patterns of human microRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPUTATIONAL IDENTIFICATION; CAENORHABDITIS-ELEGANS; GENOME BROWSER; HOST GENES; RNAS; TRANSCRIPTION; BIOGENESIS; PRECURSORS; PROFILE; MIRNAS AB MicroRNAs (miRNAs) are ~22 nt-long non-coding RNA molecules, believed to play important roles in gene regulation. We present a comprehensive analysis of the conservation and clustering patterns of known miRNAs in human. We show that human miRNA gene clustering is significantly higher than expected at random. A total of 37% of the known human miRNA genes analyzed in this study appear in clusters of two or more with pairwise chromosomal distances of at most 3000 nt. Comparison of them iRNA sequences with their homologs in four other organisms reveals a typical conservation pattern, persistent throughout the clusters. Furthermore, we show enrichment in the typical conservation patterns and other miRNA-like properties in the vicinity of known miRNA genes, compared with random genomic regions. This may imply that additional, yet unknown, miRNAs reside in these regions, consistent with the current recognition that there are overlooked miRNAs. Indeed, by comparing our predictions with cloning results and with identified miRNA genes in other mammals, we corroborate the predictions of 18 additional human miRNA genes in the vicinity of the previously known ones. Our study raises the proportion of clustered human miRNAs that are <3000 nt apart to 42%. This suggests that the clustering of miRNA genes is higher than currently acknowledged, alluding to its evolutionary and functional implications. C1 Hebrew Univ Jerusalem, Fac Med, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. Rockefeller Univ, Lab RNA Mol Biol, New York, NY 10021 USA. NIMH, Genet Lab, NHGRI, NIH, Bethesda, MD 20892 USA. RP Margalit, H (reprint author), Hebrew Univ Jerusalem, Fac Med, Dept Mol Genet & Biotechnol, POB 12272, IL-91120 Jerusalem, Israel. EM hanah@md.huji.ac.il RI Pfeffer, Sebastien/A-6512-2010; Margalit, Hanah/H-1651-2013 OI Pfeffer, Sebastien/0000-0002-8458-348X; NR 38 TC 398 Z9 479 U1 6 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 8 BP 2697 EP 2706 DI 10.1093/nar/gki567 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 926HC UT WOS:000229113100044 PM 15891114 ER PT J AU Khan, A Taylor, S Su, C Mackey, AJ Boyle, J Cole, R Glover, D Tang, K Paulsen, IT Berriman, M Boothroyd, JC Pfefferkorn, ER Dubey, JP Ajioka, JW Roos, DS Wootton, JC Sibley, LD AF Khan, A Taylor, S Su, C Mackey, AJ Boyle, J Cole, R Glover, D Tang, K Paulsen, IT Berriman, M Boothroyd, JC Pfefferkorn, ER Dubey, JP Ajioka, JW Roos, DS Wootton, JC Sibley, LD TI Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PARASITE PLASMODIUM-FALCIPARUM; PROTOZOAN PARASITE; MUTANT RESISTANT; CHLOROQUINE RESISTANCE; ADENINE-ARABINOSIDE; GENE DISCOVERY; LINKAGE MAP; VIRULENCE; LOCUS; 5-FLUORODEOXYURIDINE AB Toxoplasma gondii is a highly successful protozoan parasite in the phylum Apicomplexa, which contains numerous animal and human pathogens. T. gondii is amenable to cellular, biochemical, molecular and genetic studies, making it a model for the biology of this important group of parasites. To facilitate forward genetic analysis, we have developed a high-resolution genetic linkage map for T. gondii. The genetic map was used to assemble the scaffolds from a 10X shotgun whole genome sequence, thus defining 14 chromosomes with markers spaced at &SIM; 300 kb intervals across the genome. Fourteen chromosomes were identified comprising a total genetic size of &SIM; 592 cM and an average map unit of &SIM; 104 kb/ cM. Analysis of the genetic parameters in T. gondii revealed a high frequency of closely adjacent, apparent double crossover events that may represent gene conversions. In addition, we detected large regions of genetichomogeneity among the archetypal clonal lineages, reflecting the relatively few genetic outbreeding events that have occurred since their recent origin. Despite these unusual features, linkage analysis proved to be effective in mapping the loci determining several drug resistances. The resulting genome map provides a framework for analysis of complex traits such as virulence and transmission, and for comparative population genetic studies. C1 Washington Univ, Sch Med, Ctr Infect Dis, Dept Mol Microbiol, St Louis, MO 63110 USA. Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. Univ Penn, Penn Genom Inst, Philadelphia, PA 19104 USA. Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Inst Genom Res, Rockville, MD 20850 USA. Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England. Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA. USDA ARS, Anim Parasit Dis Lab, ANRI, Beltsville, MD 20705 USA. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Sibley, LD (reprint author), Washington Univ, Sch Med, Ctr Infect Dis, Dept Mol Microbiol, St Louis, MO 63110 USA. EM sibley@borcim.wustl.edu RI Sibley, L. David/C-4616-2008; Berriman, Matthew/A-7618-2011; Paulsen, Ian/K-3832-2012; Su, Chunlei/M-1892-2013 OI Paulsen, Ian/0000-0001-9015-9418; Su, Chunlei/0000-0001-8392-7108 FU NIAID NIH HHS [R01 AI059176, AI045806, AI059176, AI28724, AI36629, AI50930, N01AI40037, R01 AI036629, R01 AI045806, R21 AI045806, R37 AI028724] NR 43 TC 96 Z9 101 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 9 BP 2980 EP 2992 DI 10.1093/nar/gki604 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932HK UT WOS:000229544600029 PM 15911631 ER PT J AU Hu, JP Imam, SZ Hashiguchi, K de Souza-Pinto, NC Bohr, VA AF Hu, JP Imam, SZ Hashiguchi, K de Souza-Pinto, NC Bohr, VA TI Phosphorylation of human oxoguanine DNA glycosylase (alpha-OGG1) modulates its function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; CYCLIN-DEPENDENT KINASES; HOGG1 SER326CYS POLYMORPHISM; CELL-CYCLE; HUMAN OGG1; OXIDATIVE DAMAGE; LUNG-CANCER; 8-OXOGUANINE; PROTEIN; RECOGNITION AB Oxoguanine DNA glycosylase (OGG1) initiates the repair of 8-oxoguanine (8-oxoG), a major oxidative DNA base modification that has been directly implicated in cancer and aging. OGG1 functions in the base excision repair pathway, for which a molecular hand-off mechanism has been proposed. To date, only one functional and a few physical protein interactions have been reported for OGG1. Using the yeast two-hybrid system and a protein array membrane, we identified two novel protein interactions of OGG1, with two different protein kinases: Cdk4, a serine-threonine kinase, and c-AbI, a tyrosine kinase. We confirmed these interactions in vitro using recombinant proteins and in vivo by co-immunoprecipitation from whole cell extracts. OGG1 is phosphorylated in vitro by Cdk4, resulting in a 2.5-fold increase in the 8-oxoG/C incision activity of OGG1. C-AbI tyrosine phosphorylates OGG1 in vitro; however, this phosphorylation event does not affect OGG1 8-oxoG/C incision activity. These results provide the first evidence that a post-translational modification of OGG1 can affect its catalytic activity. The distinct functional outcomes from serine/threonine or tyrosine phosphorylation may indicate that activation of different signal transduction pathways modulate OGG1 activity in different ways. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 49 TC 49 Z9 49 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 10 BP 3271 EP 3282 DI 10.1093/nar/gki636 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 947MI UT WOS:000230649600020 PM 15942030 ER PT J AU Kalish, JM Seidman, MM Weeks, DL Glazer, PM AF Kalish, JM Seidman, MM Weeks, DL Glazer, PM TI Triplex-induced recombination and repair in the pyrimidine motif SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HELIX-FORMING OLIGONUCLEOTIDES; CELL-FREE-EXTRACTS; MAMMALIAN-CELLS; ANTISENSE OLIGONUCLEOTIDES; TARGETED MUTAGENESIS; MOUSE CELLS; C-MYC; DNA; GENE; SEQUENCE AB Triplex-forming oligonucleotides (TFOs) bind DNA in a sequence-specific manner at polypurine/polypyrimidine sites and mediate targeted genome modification. Triplexes are formed by either pyrimidine TFOs, which bind parallel to the purine strand of the duplex (pyrimidine, parallel motif), or purine TFOs, which bind in an anti-parallel orientation (purine, anti-parallel motif). Both purine and pyrimidine TFOs, when linked to psoralen, have been shown to direct psoralen adduct formation in cells, leading to mutagenesis or recombination. However, only purine TFOs have been shown to mediate genome modification without the need for a targeted DNA-adduct. In this work, we report the ability of a series of pyrimidine TFOs, with selected chemical modifications, to induce repair and recombination in two distinct episomal targets in mammalian cells in the absence of any DNA-reactive conjugate. We find that TFOs containing N3'-> P5' phosphoramidate (amidate), 5-(1-propynyl)-2'-deoxyuridine (pdU), 2'-O-methyl-ribose (2'-O-Me), 2'-O-(2-aminoethyl)-ribose, or 2'-O, 4'-C-methylene bridged or locked nucleic acid (LNA)-modified nucleotides show substantially increased formation of non-covalent triplexes under physiological conditions compared with unmodified DNA TFOs. However, of these modified TFOs, only the amidate and pdU-modified TFOs mediate induced recombination in cells and stimulate repair in cell extracts, at levels comparable to those seen with purine TFOs in similar assays. These results show that amidate and pdU-modified TFOs can be used as reagents to stimulate site-specific gene targeting without the need for conjugation to DNA-reactive molecules. By demonstrating the potential for induced repair and recombination with appropriately modified pyrimidine TFOs, this work expands the options available for triplex-mediated gene targeting. C1 Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. NIA, NIH, Baltimore, MD 21224 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. RP Yale Univ, Sch Med, Dept Therapeut Radiol, POB 208040,HRT 140, New Haven, CT 06520 USA. EM peter.glazer@yale.edu RI Weeks, Daniel/F-6216-2010 FU NCI NIH HHS [R01 CA064186, R01CA64186]; NHLBI NIH HHS [P50HL062178]; NIGMS NIH HHS [R55 GM056277, R55 GM056277-01, T32 GM007205, R01 GM054731, GM07205, R01GM54731] NR 52 TC 35 Z9 38 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 11 BP 3492 EP 3502 DI 10.1093/nar/gki659 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943ID UT WOS:000230345800011 PM 15961731 ER PT J AU Theruvathu, JA Jaruga, P Nath, RG Dizdaroglu, M Brooks, PJ AF Theruvathu, JA Jaruga, P Nath, RG Dizdaroglu, M Brooks, PJ TI Polyamines stimulate the formation of mutagenic 1,N-2-propanodeoxyguanosine adducts from acetaldehyde SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-ADDUCTS; CHROMOSOMAL-ABERRATIONS; DEOXYGUANOSINE ADDUCTS; PERIPHERAL LYMPHOCYTES; SALIVARY ACETALDEHYDE; GUANINE NUCLEOSIDES; FANCONI-ANEMIA; VINYL-ACETATE; CANCER-RISK; CROSS-LINKS AB Alcoholic beverage consumption is associated with an increased risk of upper gastrointestinal cancer. Acetaldehyde (AA), the first metabolite of ethanol, is a suspected human carcinogen, but the molecular mechanisms underlying AA carcinogenicity are unclear. In this work, we tested the hypothesis that polyamines could facilitate the formation of mutagenic alpha-methyl-gamma-hydroxy-1,N-2-propano-2'-deoxyguanosine (Cr-PdG) adducts from biologically relevant AA concentrations. We found that Cr-PdG adducts could be formed by reacting deoxyguanosine with mu M concentrations of AA in the presence of spermidine, but not with either AA or spermidine alone. The identities of the Cr-PdG adducts were confirmed by both liquid and gas chromatography-mass spectrometry. Using a novel isotope-dilution liquid chromatography-mass spectrometry assay, we found that in the presence of 5 mM spermidine, AA concentrations of 100 mu M and above resulted in the formation of Cr-PdG in genomic DNA. These AA levels are within the range that occurs in human saliva after alcoholic beverage consumption. We also showed that spermidine directly reacts with AA to generate crotonaldehyde (CrA), most likely via an enamine aldol condensation mechanism. We propose that AA derived from ethanol metabolism is converted to CrA by polyamines in dividing cells, forming Cr-PdG adducts, which may be responsible for the carcinogenicity of alcoholic beverage consumption. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, Bethesda, MD 20952 USA. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20952 USA. EM pjbrooks@mail.nih.gov RI Jaruga, Pawel/M-4378-2015 NR 59 TC 60 Z9 63 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 11 BP 3513 EP 3520 DI 10.1093/nar/gki661 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943ID UT WOS:000230345800013 PM 15972793 ER PT J AU Grajkowski, A Pedras-Vasconcelos, J Wang, VV Ausin, C Hess, S Verthelyi, D Beaucage, SL AF Grajkowski, A Pedras-Vasconcelos, J Wang, VV Ausin, C Hess, S Verthelyi, D Beaucage, SL TI Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; PHASE OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; SULFUR-TRANSFER REAGENT; BACTERIAL-DNA; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; PROOLIGONUCLEOTIDE APPROACH; PHOSPHATE PROTECTION; TACARIBE VIRUS; PHOSPHOROTHIOATES; OLIGODEOXYNUCLEOTIDES AB A CpG-containing DNA oligonucleotide functionalized with the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group (CpG ODN fma1555) was prepared from phosphoramidites 1a-d using solid-phase techniques. The oligonucleotide behaved as a prodrug by virtue of its conversion to the well-studied immunomodulatory CpG ODN 1555 through thermolytic cleavage of the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group. Such a conversion occurred at 37 degrees C with a half-time of 73 h. The immunostimulatory properties of CpG ODN fma1555 were evaluated in two in vivo assays, one of which consisted of mice challenged in the ear with live Leishmania major metacyclic promastigotes. Local intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN 1555 in reducing the size of Leishmania lesions over time. In a different infectious model, CpG ODN 1555 prevented the death of Tacaribe-infected mice (43% survival) when administered between day 0 and 3 post infection. Administration of CpG ODN fma1555 three days before infection resulted in improved immunoprotection (60-70% survival). Moreover, co-administration of CpG ODN fma1555 and CpG ODN 1555 in this model increased the window for therapeutic treatment against Tacaribe virus infection, and thus supports the use of thermolytic oligonucleotides as prodrugs in the effective treatment of infectious diseases. C1 US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Immunol Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov NR 45 TC 22 Z9 23 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 11 BP 3550 EP 3560 DI 10.1093/nar/gki657 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943ID UT WOS:000230345800017 PM 15972797 ER PT J AU Stuart, JA Mayard, S Hashiguchi, K Souza-Pinto, NC Bohr, VA AF Stuart, JA Mayard, S Hashiguchi, K Souza-Pinto, NC Bohr, VA TI Localization of mitochondrial DNA base excision repair to an inner membrane-associated particulate fraction SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RAT-LIVER MITOCHONDRIA; POLYMERASE-GAMMA; INTRACELLULAR-LOCALIZATION; PROTEIN-COMPONENTS; OXIDATIVE DAMAGE; REPLICATION; OGG1; IDENTIFICATION; NUCLEOIDS; COMPLEX AB Mitochondrial DNA (mtDNA) contains high levels of oxidative damage relative to nuclear DNA. A full, functional DNA base excision repair (BER) pathway is present in mitochondria, to repair oxidative DNA lesions. However, little is known about the organization of this pathway within mitochondria. Here, we provide evidence that the mitochondrial BER proteins are not freely soluble, but strongly associated with an inner membrane-containing particulate fraction. Uracil DNA glycosylase, oxoguanine DNA glycosylase and DNA polymerase gamma activities all co-sedimented with this particulate fraction and were not dissociated from it by detergent (0.1% or 1.0% NP40) treatment. The particulate associations of these activities were not due to their binding mtDNA, which is itself associated with the inner membrane, as they also localized to the particulate fraction of mitochondria from 143B (TK-) rho(0) cells, which lack mtDNA. However, all of the BER activities were at least partially solubilized from the particulate fraction by treatment with 150-300 mM NaCl, suggesting that electrostatic interactions are involved in the association. The biological implications of the apparent immobilization of BER proteins are discussed. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr,Box 1, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 27 TC 54 Z9 55 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 12 BP 3722 EP 3732 DI 10.1093/gki683 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 948OK UT WOS:000230725400010 PM 16006620 ER PT J AU Tan, W Zolotukhin, AS Tretyakova, I Bear, J Lindtner, S Smulevitch, SV Felber, BK AF Tan, W Zolotukhin, AS Tretyakova, I Bear, J Lindtner, S Smulevitch, SV Felber, BK TI Identification and characterization of the mouse nuclear export factor (Nxf) family members SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA EXPORT; CONSTITUTIVE TRANSPORT ELEMENT; GENOME-WIDE ANALYSIS; BINDING PROTEIN; HUMAN HOMOLOG; PORE COMPLEX; HUMAN TAP; DROSOPHILA; MEX67P; REV AB TAP/hNXF1 is a key factor that mediates general cellular mRNA export from the nucleus, and its orthologs are structurally and functionally conserved from yeast to humans. Metazoans encode additional proteins that share homology and domain organization with TAP/hNXF1, suggesting their participation in mRNA metabolism; however, the precise role(s) of these proteins is not well understood. Here, we found that the human mRNA export factor hNXF2 is specifically expressed in the brain, suggesting a brain-specific role in mRNA metabolism. To address the roles of additional NXF factors, we have identified and characterized the two Nxf genes, Nxf2 and Nxf7, which together with the TAP/hNXF1's ortholog Nxf1 comprise the murine Nxf family. Both mNXF2 and mNXF7 have a domain structure typical of the NXF family. We found that mNXF2 protein is expressed during mouse brain development. Similar to TAP/hNXF1, the mNXF2 protein is found in the nucleus, the nuclear envelope and cytoplasm, and is an active mRNA export receptor. In contrast, mNXF7 localizes exclusively to cytoplasmic granules and, despite its overall conserved sequence, lacks mRNA export activity. We concluded that mNXF2 is an active mRNA export receptor similar to the prototype TAP/hNXF1, whereas mNXF7 may have a more specialized role in the cytoplasm. C1 NCI, Canc Res Ctr, Vaccine Branch, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Canc Res Ctr, Vaccine Branch, Human Retrovirus Pathogenesis Sect, Frederick, MD 21702 USA. EM felber@ncifcrf.gov NR 31 TC 23 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 12 BP 3855 EP 3865 DI 10.1093/nar/gki706 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 948OK UT WOS:000230725400024 PM 16027110 ER PT J AU Iyer, LM Koonin, EV Leipe, DD Aravind, L AF Iyer, LM Koonin, EV Leipe, DD Aravind, L TI Origin and evolution of the archaeo-eukaryotic primase superfamily and related palm-domain proteins: structural insights and new members SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; STRANDED-DNA-BINDING; SECONDARY STRUCTURE PREDICTION; ADENOASSOCIATED-VIRUS REP; DEPENDENT RNA-POLYMERASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; HELICASE-PRIMASE; GENOMIC CONTEXT; SULFOLOBUS-SOLFATARICUS AB We report an in-depth computational study of the protein sequences and structures of the superfamily of archaeo-eukaryotic primases (AEPs). This analysis greatly expands the range of diversity of the AEPs and reveals the unique active site shared by all members of this superfamily. In particular, it is shown that eukaryotic nucleo-cytoplasmic large DNA viruses, including poxviruses, asfarviruses, iridoviruses, phycodnaviruses and the mimivirus, encode AEPs of a distinct family, which also includes the herpesvirus primases whose relationship to AEPs has not been recognized previously. Many eukaryotic genomes, including chordates and plants, encode previously uncharacterized homologs of these predicted viral primases, which might be involved in novel DNA repair pathways. At a deeper level of evolutionary connections, structural comparisons indicate that AEPs, the nucleases involved in the initiation of rolling circle replication in plasmids and viruses, and origin-binding domains of papilloma and polyoma viruses evolved from a common ancestral protein that might have been involved in a protein-priming mechanism of initiation of DNA replication. Contextual analysis of multidomain protein architectures and gene neighborhoods in prokaryotes and viruses reveals remarkable parallels between AEPs and the unrelated DnaG-type primases, in particular, tight associations with the same repertoire of helicases. These observations point to a functional equivalence of the two classes of primases, which seem to have repeatedly displaced each other in various extrachromosomal replicons. 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 NR 96 TC 123 Z9 127 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 12 BP 3875 EP 3896 DI 10.1093/nar/gki702 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 948OK UT WOS:000230725400026 PM 16027112 ER PT J AU Tolstorukov, MY Virnik, KM Adhya, S Zhurkin, VB AF Tolstorukov, MY Virnik, KM Adhya, S Zhurkin, VB TI A-tract clusters may facilitate DNA packaging in bacterial nucleoid SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HISTONE-LIKE PROTEINS; SEQUENCE-DIRECTED CURVATURE; ESCHERICHIA-COLI; CURVED DNA; B-DNA; TOPOLOGICAL MEASUREMENT; CRYSTAL-STRUCTURE; COMPLETE GENOMES; BEND ANGLE; RECOGNITION AB Molecular mechanisms of bacterial chromosome packaging are still unclear, as bacteria lack nucleosomes or other apparent basic elements of DNA compaction. Among the factors facilitating DNA condensation may be a propensity of the DNA molecule for folding due to its intrinsic curvature. As suggested previously, the sequence correlations in genome reflect such a propensity [Trifonov and Sussman (1980) Proc. Natl Acad. Sci. USA, 77, 3816-3820]. To further elaborate this concept, we analyzed positioning of A-tracts (the sequence motifs introducing the most pronounced DNA curvature) in the Escherichia coli genome. First, we observed that the A-tracts are over-represented and distributed 'quasi-regularly' throughout the genome, including both the coding and intergenic sequences. Second, there is a 10-12 bp periodicity in the A-tract positioning indicating that the A-tracts are phased with respect to the DNA helical repeat. Third, the phased A-tracts are organized in similar to 100 bp long clusters. The latter feature was revealed with the help of a novel approach based on the Fourier series expansion of the A-tract distance autocorrelation function. Since the A-tracts introduce local bends of the DNA duplex and these bends accumulate when properly phased, the observed clusters would facilitate DNA looping. Also, such clusters may serve as binding sites for the nucleoid-associated proteins that have affinities for curved DNA (such as HU, H-NS, Hfq and CbpA). Therefore, we suggest that the similar to 100 bp long clusters of the phased A-tracts constitute the 'structural code' for DNA compaction by providing the long-range intrinsic curvature and increasing stability of the DNA complexes with architectural proteins. C1 NCI, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. V Karazin Kharkov Natl Univ, Dept Biol & Med Phys, UA-61077 Kharkov, Ukraine. RP Tolstorukov, MY (reprint author), NCI, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. EM tolstorukov@gmail.com; zhurkin@nih.gov NR 66 TC 45 Z9 45 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 12 BP 3907 EP 3918 DI 10.1093/nar/gki699 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 948OK UT WOS:000230725400028 PM 16024741 ER PT J AU Balaji, S Babu, MM Iyer, LM Aravind, L AF Balaji, S Babu, MM Iyer, LM Aravind, L TI Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SECONDARY STRUCTURE PREDICTION; ETHYLENE-RESPONSIVE ELEMENT; MULTIPLE SEQUENCE ALIGNMENT; PLASMODIUM-FALCIPARUM; HOMING ENDONUCLEASES; PROTEIN SEQUENCES; CRYSTAL-STRUCTURE; PH DOMAIN; PSI-BLAST; ARABIDOPSIS AB The comparative genomics of apicomplexans, such as the malarial parasite Plasmodium, the cattle parasite Theileria and the emerging human parasite Cryptosporidium, have suggested an unexpected paucity of specific transcription factors (TFs) with DNA binding domains that are closely related to those found in the major families of TFs from other eukaryotes. This apparent lack of specific TFs is paradoxical, given that the apicomplexans show a complex developmental cycle in one or more hosts and a reproducible pattern of differential gene expression in course of this cycle. Using sensitive sequence profile searches, we show that the apicomplexans possess a lineage-specific expansion of a novel family of proteins with a version of the AP2 (Apetala2)integrase DNA binding domain, which is present in numerous plant TFs. About 20-27 members of this apicomplexan AP2 (ApiAP2) family are encoded in different apicomplexan genomes, with each protein containing one to four copies of the AP2 DNA binding domain. Using gene expression data from Plasmodium falciparum, we show that guilds of ApiAP2 genes are expressed in different stages of intraerythrocytic development. By analogy to the plant AP2 proteins and based on the expression patterns, we predict that the ApiAP2 proteins are likely to function as previously unknown specific TFs in the apicomplexans and regulate the progression of their developmental cycle. In addition to the ApiAP2 family, we also identified two other novel families of AP2 DNA binding domains in bacteria and transposons. Using structure similarity searches, we also identified divergent versions of the AP2-integrase DNA binding domain fold in the DNA binding region Of the PI-Scel homing endonuclease and the C-terminal domain of the pleckstrin homology (PH) domain-like modules of eukaryotes. Integrating these findings, we present a reconstruction of the evolutionary scenario of the AP2-integrase DNA binding domain fold, which suggests that it underwent multiple independent combinations with different types of mobile endonucleases or recombinases. It appears that the eukaryotic versions have emerged from versions of the domain associated with mobile elements, followed by independent lineage-specific expansions, which accompanied their recruitment to transcription regulation functions. 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 70 TC 203 Z9 208 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 13 BP 3994 EP 4006 DI 10.1093/nar/gki709 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959KP UT WOS:000231516900005 PM 16040597 ER PT J AU Auriol, E Billard, LM Magdinier, F Dante, R AF Auriol, E Billard, LM Magdinier, F Dante, R TI Specific binding of the methyl binding domain protein 2 at the BRCA1-NBR2 locus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HISTONE DEACETYLASE COMPLEX; HUMAN MAMMARY-GLAND; TRANSCRIPTIONAL REPRESSION; DNA METHYLATION; RETT-SYNDROME; HUMAN CANCER; CHROMATIN-STRUCTURE; MAMMALIAN-CELLS; GENE; MECP2 AB The methyl-CpG binding domain (MBD) proteins are key molecules in the interpretation of DNA methylation signals leading to gene silencing. We investigated their binding specificity at the constitutively methylated region of a CpG island containing the bidirectional promoter of the Breast cancer predisposition gene 1, BRCA1, and the Near BRCA1 2 (NBR2) gene. In HeLa cells, quantitative chromatin immunoprecipitation assays indicated that MBD2 is associated with the methylated region, while MeCP2 and MBD1 were not detected at this locus. MBD2 depletion (similar to 90%), mediated by a transgene expressing a small interfering RNA (siRNA), did not induce MeCP2 or MBD1 binding at the methylated area. Furthermore, the lack of MBD2 at the BRCA1-NBR2 CpG island is associated with an elevated level of NBR2 transcripts and with a significant reduction of induced-DNA-hypomethylation response. In MBD2 knockdown cells, transient expression of a Mbd2 cDNA, refractory to siRNA-mediated decay, shifted down the NBR2 mRNA level to that observed in unmodified HeLa cells. Variations in MBD2 levels did not affect BRCA1 expression despite its stimulation by DNA hypomethylation. Collectively, our data indicate that MBD2 has specific targets and its presence at these targets is indispensable for gene repression. C1 UCBL1, CNRS, FRE 2692, Lab Genet & Canc, F-69373 Lyon, France. NICHD, Mol Embryol Lab, NIH, Bethesda, MD USA. RP Dante, R (reprint author), Ctr Leon Berard, INSERM, U590, Oncol Mol Lab, 28 Rue Laennec, F-69373 Lyon, France. EM dante@univ-lyon1.fr RI Magdinier, Frederique/I-4735-2016 OI Magdinier, Frederique/0000-0002-0159-9559 NR 52 TC 20 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 13 BP 4243 EP 4254 DI 10.1093/nar/gki729 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959KP UT WOS:000231516900029 PM 16052033 ER PT J AU Yang, Y Sass, LE Du, CW Hsieh, P Erie, DA AF Yang, Y Sass, LE Du, CW Hsieh, P Erie, DA TI Determination of protein-DNA binding constants and specificities from statistical analyses of single molecules: MutS-DNA interactions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ATOMIC-FORCE MICROSCOPY; MISMATCH REPAIR PROTEIN; ESCHERICHIA-COLI MUTS; EQUILIBRIUM; COMPLEX; RECOGNITION; THERMODYNAMICS; MECHANISMS; ADSORPTION; XPC-HR23B AB Atomic force microscopy (AFM) is a powerful technique for examining the conformations of protein-DNA complexes and determining the stoichiometries and affinities of protein-protein complexes. We extend the capabilities of AFM to the determination of protein-DNA binding constants and specificities. The distribution of positions of the protein on the DNA fragments provides a direct measure of specificity and requires no knowledge of the absolute binding constants. The fractional occupancies of the protein at a given position in conjunction with the protein and DNA concentrations permit the determination of the absolute binding constants. We present the theoretical basis for this analysis and demonstrate its utility by characterizing the interaction of MutS with DNA fragments containing either no mismatch or a single mismatch. We show that MutS has significantly higher specificities for mismatches than was previously-suggested from bulk studies and that the apparent low specificities are the result of high affinity binding to DNA ends. These results resolve the puzzle of the apparent low binding specificity of MutS with the expected high repair specificities. In conclusion, from a single set of AFM experiments, it is possible to determine the binding affinity, specificity and stoichiometry, as well as the conformational properties of the protein-DNA complexes. C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Appl & Mat Sci, Chapel Hill, NC 27599 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Erie, DA (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA. EM derie@unc.edu FU NIGMS NIH HHS [GM R01-54316] NR 37 TC 59 Z9 59 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 13 BP 4322 EP 4334 DI 10.1093/nar/gki708 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959KP UT WOS:000231516900035 PM 16061937 ER PT J AU Buzina, A Aladjem, MI Kolman, JL Wahl, GM Ellis, J AF Buzina, A Aladjem, MI Kolman, JL Wahl, GM Ellis, J TI Initiation of DNA replication at the human beta-globin 3 ' enhancer SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; HIGH-LEVEL EXPRESSION; TRANSGENIC MICE; MOUSE ERYTHROLEUKEMIA; REGULATORY ELEMENTS; MAMMALIAN-CELLS; GENE CONTAINS; ORIGIN; IDENTIFICATION AB The origin of DNA replication in the human beta-globin gene contains an initiation region (IR) and two flanking auxiliary elements. Two replicator modules are located within the upstream auxiliary sequence and the IR core, but the functional sequences in the downstream auxiliary element are unknown. Here, we use a combination of benzoylated-naphthoylated DEAE (BND) cellulose purification and nascent strand abundance assays to show that replication initiation occurs at the beta-globin 3' enhancer on human chromosome 11 in the Hu11 hybrid murine erythroleukemia (MEL) cell line. To examine replicator function, 3' enhancer fragments were inserted into an ectopic site in MEL cells via an optimized FRT/EGFP-FLP integration system. These experiments demonstrate that the 1.6 kb downstream auxiliary element is a third replicator module called bGRep-E in erythroid cells. The minimal 260 bp 3' enhancer is required but not sufficient to initiate efficient replication, suggesting cooperation with adjacent sequences. The minimal 3' enhancer also cooperates with elements in an expressing HS3 beta/gamma-globin construct to initiate replication. These data indicate that the beta-globin replicator has multiple initiation sites in three closely spaced replicator modules. We conclude that a mammalian enhancer can cooperate with adjacent sequences to create an efficient replicator module. C1 Hosp Sick Children, Dev Biol Program, Toronto, ON M5G 1X8, Canada. NCI, Bethesda, MD 20892 USA. Salk Inst, Gene Express Lab, San Diego, CA 92186 USA. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. RP Ellis, J (reprint author), Hosp Sick Children, Dev Biol Program, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM jellis@sickkids.ca RI Ellis, James/F-4789-2011; Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 NR 39 TC 7 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 14 BP 4412 EP 4424 DI 10.1093/nar/gki747 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957ID UT WOS:000231362600009 PM 16085752 ER PT J AU Magazinnik, T Anand, M Sattlegger, E Hinnebusch, AG Kinzy, TG AF Magazinnik, T Anand, M Sattlegger, E Hinnebusch, AG Kinzy, TG TI Interplay between GCN2 and GCN4 expression, translation elongation factor 1 mutations and translational fidelity in yeast SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TRANSFER-RNA; PHENOTYPIC SUPPRESSION; NUCLEOTIDE EXCHANGE; PSI(+) PRION; KINASE GCN2; ANTIBIOTICS; MUTAGENESIS; ACTIVATION; MECHANISMS AB Genetic screens in Saccharomyces cerevisiae have identified the roles of ribosome components, tRNAs and translation factors in translational fidelity. These screens rely on the suppression of altered start codons, nonsense codons or frameshift mutations in genes involved in amino acid or nucleotide metabolism. Many of these genes are regulated by the General Amino Acid Control (GAAC) pathway. Upon amino acid starvation, the kinase GCN2 induces the GAAC cascade via increased translation of the transcriptional activator GCN4 controlled by upstream open reading frames (uORFs). Overexpression of the GCN2 or GCN4 genes enhances the sensitivity of translation fidelity assays that utilize genes regulated by GCN4, such as the suppression of a +1 insertion by S.cerevisiae translation elongation factor 1A (eEF1A) mutants. Paromomycin and the prion [PSI+], which reduce translational fidelity, do not increase GCN4 expression to induce the suppression phenotype and in fact reduce derepression. eEF1A mutations that reduce translation, however, reduce expression of GCN4 under non-starvation conditions. These eEF1A mutants also reduce HIS4 mRNA expression. Taken together, this system improves in vivo strategies for the analysis of translational fidelity and further provides new information on the interplay among translation fidelity, altered elongation and translational control via uORFs. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, Piscataway, NJ 08854 USA. NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NICHD, Canc Inst New Jersey, NIH, Bethesda, MD 20892 USA. RP Magazinnik, T (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Microbiol Mol Genet & Immunol, Piscataway, NJ 08854 USA. EM kinzytg@umdnj.edu FU NIGMS NIH HHS [GM57483, R01 GM057483] NR 30 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 14 BP 4584 EP 4592 DI 10.1093/nar/gki765 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957ID UT WOS:000231362600026 PM 16100380 ER PT J AU Makarova, KS Wolf, YI Mekhedov, SL Mirkin, BG Koonin, EV AF Makarova, KS Wolf, YI Mekhedov, SL Mirkin, BG Koonin, EV TI Ancestral paralogs and pseudoparalogs and their role in the emergence of the eukaryotic cell SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HORIZONTAL GENE-TRANSFER; COMPARATIVE GENOMICS; DNA-REPLICATION; DUPLICATE GENES; SACCHAROMYCES-CEREVISIAE; DOSAGE SENSITIVITY; PROTEIN EVOLUTION; NUCLEAR GENOMES; UNIVERSAL TREE; COG DATABASE AB Gene duplication is a crucial mechanism of evolutionary innovation. A substantial fraction of eukaryotic genomes consists of paralogous gene families. We assess the extent of ancestral paralogy, which dates back to the last common ancestor of all eukaryotes, and examine the origins of the ancestral paralogs and their potential roles in the emergence of the eukaryotic cell complexity. A parsimonious reconstruction of ancestral gene repertoires shows that 4137 orthologous gene sets in the last eukaryotic common ancestor (LECA) map back to 2150 orthologous sets in the hypothetical first eukaryotic common ancestor (FECA) [paralogy quotient (PQ) of 1.92]. Analogous reconstructions show significantly lower levels of paralogy in prokaryotes, 1.19 for archaea and 1.25 for bacteria. The only functional class of eukaryotic proteins with a significant excess of paralogous clusters over the mean includes molecular chaperones and proteins with related functions. Almost all genes in this category underwent multiple duplications during early eukaryotic evolution. In structural terms, the most prominent sets of paralogs are superstructure-forming proteins with repetitive domains, such as WD-40 and TPR. In addition to the true ancestral paralogs which evolved via duplication at the onset of eukaryotic evolution, numerous pseudoparalogs were detected, i.e. homologous genes that apparently were acquired by early eukaryotes via different routes, including horizontal gene transfer (HGT) from diverse bacteria. The results of this study demonstrate a major increase in the level of gene paralogy as a hallmark of the early evolution of eukaryotes. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Univ London Birkbeck Coll, Sch Informat Syst & Comp Sci, London WC1E 7HX, England. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov OI Mirkin, Boris/0000-0001-5470-8635 FU Intramural NIH HHS NR 81 TC 91 Z9 94 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 14 BP 4626 EP 4638 DI 10.1093/nar/gki775 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957ID UT WOS:000231362600031 PM 16106042 ER PT J AU Harrison, JF Hollensworth, SB Spitz, DR Copeland, WC Wilson, GL LeDoux, SP AF Harrison, JF Hollensworth, SB Spitz, DR Copeland, WC Wilson, GL LeDoux, SP TI Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FREE-RADICAL PRODUCTION; GLYCOSYLASE ACTIVITY; GLUCOSE DEPRIVATION; POLYMERASE-GAMMA; DAMAGE; CELLS; ENZYME; SITES; BRAIN; ENDONUCLEASE AB Neurodegeneration can occur as a result of endogenous oxidative stress. Primary cerebellar granule cells were used in this study to determine if mitochondrial DNA (mtDNA) repair deficiencies correlate with oxidative stress-induced apoptosis in neuronal cells. Granule cells exhibited a significantly higher intracellular oxidative state compared with primary astrocytes as well as increases in reductants, such as glutathione, and redox sensitive signaling molecules, such as AP endonuclease/redox effector factor-1. Cerebellar granule cultures also exhibited an increased susceptibility to exogenous oxidative stress. Menadione (50 mu M) produced twice as many lesions in granule cell mtDNA compared with astrocytes, and granule cell mtDNA repair was significantly less efficient. A decreased capacity to repair oxidative mtDNA damage correlates strongly with mitochondrial initiated apoptosis in these neuronal cultures. Interestingly, the mitochondrial activities of initiators for base excision repair (BER), the bifunctional glycosylase/AP lyases as well as AP endonuclease, were significantly higher in cerebellar granule cells compared with astrocytes. The increased mitochondrial AP endonuclease activity in combination with decreased polymerase gamma activity may cause an imbalance in oxidative BER leading to an increased production and persistence of mtDNA damage in neurons when treated with menadione. This study provides evidence linking neuronal mtDNA repair capacity with oxidative stress-related neurodegeneration. C1 Univ S Alabama, Dept Cell Biol & Neurosci, Mobile, AL 36688 USA. Univ Iowa, Holden Comprehans Canc Ctr, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Univ S Alabama, Dept Cell Biol & Neurosci, Mobile, AL 36688 USA. EM sledoux@usouthal.edu FU NCI NIH HHS [R01 CA100045, CA100045]; NIA NIH HHS [AG19602, R01 AG019602]; NIEHS NIH HHS [F32 ES005865, R01 ES003456, R01 ES005865, ES05865, ES03456, ES 05865]; NINDS NIH HHS [NS047208, R01 NS047208] NR 60 TC 62 Z9 65 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 14 BP 4660 EP 4671 DI 10.1093/nar/gki759 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957ID UT WOS:000231362600034 PM 16107556 ER PT J AU Lewis, LK Karthikeyan, G Cassiano, J Resnick, MA AF Lewis, LK Karthikeyan, G Cassiano, J Resnick, MA TI Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; FACTOR-I; HOMOLOGOUS RECOMBINATION; REPRESSED CHROMATIN; IONIZING-RADIATION; REPLICATION FORKS; DAMAGE CHECKPOINT; GENE CONVERSION; FACTOR ASF1; CELL-DEATH AB Assembly of new chromatin during S phase requires the histone chaperone complexes CAF-1 (Cac2p, Msi1p and Rlf2p) and RCAF (Asf1p plus acetylated histones H3 and H4). Cells lacking CAF-1 and RCAF are hypersensitive to DNA-damaging agents, such as methyl methanesulfonate and camptothecin, suggesting a possible defect in double-strand break (DSB) repair. Assays developed to quantitate repair of defined, cohesive-ended break structures revealed that DSB-induced plasmid:chromosome recombination was reduced similar to 10-fold in RCAF/CAF-1 double mutants. Recombination defects were similar with both chromosomal and plasmid targets in vivo, suggesting that inhibitory chromatin structures were not involved. Consistent with these observations, ionizing radiation-induced loss of heterozygosity was abolished in the mutants. Nonhomologous end-joining (NHEJ) repair proficiency and accuracy were intermediate between wild-type levels and those of NHEJ-deficient yku70 and rad50 mutants. The defects in NHEJ, but not homologous recombination, could be rescued by deletion of HMR-a1, a component of the a1/alpha2 transcriptional repressor complex. The findings are consistent with the observation that silent mating loci are partially derepressed. These results demonstrate that defective assembly of nucleosomes during new DNA synthesis compromises each of the known pathways of DSB repair and that the effects can be indirect consequences of changes in silenced chromatin structure. C1 SW Texas State Univ, Dept Biochem & Chem, San Marcos, TX 78666 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP SW Texas State Univ, Dept Biochem & Chem, San Marcos, TX 78666 USA. EM LL18@txstate.edu NR 67 TC 26 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 15 BP 4928 EP 4939 DI 10.1093/nar/gki806 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 965BT UT WOS:000231925700031 PM 16141196 ER PT J AU Sheetlin, S Park, Y Spouge, JL AF Sheetlin, S Park, Y Spouge, JL TI The Gumbel pre-factor k for gapped local alignment can be estimated from simulations of global alignment SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FINITE-SIZE CORRECTIONS; APPROXIMATE P-VALUES; SEQUENCE ALIGNMENTS; STATISTICAL SIGNIFICANCE; POISSON APPROXIMATIONS; SIMILARITIES; REGRESSION; SEARCH; PARAMETER; PROTEINS AB The optimal gapped local alignment score of two random sequences follows a Gumbel distribution. The Gumbel distribution has two parameters, the scale parameter lambda and the pre-factor k. Presently, the basic local alignment search tool (BLAST) programs (BLASTP (BLAST for proteins), PSI-BLAST, etc.) use all time-consuming computer simulations to determine the Gumbel parameters. Because the simulations must be done offline, BLAST users are restricted in their choice of alignment scoring schemes. The ultimate aim of this paper is to speed the simulations, to determine the Gumbel parameters online, and to remove the corresponding restrictions on BLAST users. Simulations for the scale parameter lambda can be as much as five times faster, if they use global instead of local alignment [R. Bundschuh (2002) J. Comput. Biol., 9, 243-260]. Unfortunately, the acceleration does not extend in determining the Gumbel pre-factor k, because k has no known mathematical relationship to global alignment. This paper relates k to global alignment and exploits the relationship to show that for the BLASTP defaults, 10 000 realizations with sequences of average length 140 suffice to estimate both Gumbel parameters lambda and k within the errors required (lambda, 0.8%; k, 10%). For the BLASTP defaults, simulations for both Gumbel parameters now take less than 30 s on a 2.8 GHz Pentium 4 processor. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov RI Park, Yonil/E-6075-2010 FU Intramural NIH HHS NR 37 TC 16 Z9 17 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 15 BP 4987 EP 4994 DI 10.1093/nar/gki800 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 965BT UT WOS:000231925700036 PM 16147981 ER PT J AU Sidorova, NY Muradymov, S Rau, DC AF Sidorova, NY Muradymov, S Rau, DC TI Trapping DNA-protein binding reactions with neutral osmolytes for the analysis by gel mobility shift and self-cleavage assays SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ECORV RESTRICTION-ENDONUCLEASE; NONSPECIFIC DNA; RECOGNITION SITE; MOLECULAR RECOGNITION; OSMOTIC-STRESS; WATER ACTIVITY; ELECTROPHORESIS; SEQUENCES; COMPLEXES; BAMHI AB We take advantage of our previous observation that neutral osmolytes can strongly slow down the rate of DNA-protein complex dissociation to develop a method that uses osmotic stress to 'freeze' mixtures of DNA-protein complexes and prevent further reaction enabling analysis of the products. We apply this approach to the gel mobility shift assay and use it to modify a self-cleavage assay that uses the nuclease activity of the restriction endonucleases to measure sensitively their specific binding to DNA. At sufficiently high concentrations of neutral osmolytes the cleavage reaction can be triggered at only those DNA fragments with initially bound enzyme. The self-cleavage assay allows measurement of binding equilibrium and kinetics directly in solution avoiding the intrinsic problems of gel mobility shift and filter binding assays while providing the same sensitivity level. Here we compare the self-cleavage and gel mobility shift assays applied to the DNA binding of EcoRI and BamHI restriction endonucleases. Initial results indicate that BamHI dissociation from its specific DNA sequence is strongly linked to water activity with the half-life time of the specific complex increasing similar to 20-fold from 0 to 1 osmolal betaine. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Sidorova, NY (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1E-108, Bethesda, MD 20892 USA. EM sidorova@mail.nih.gov FU Intramural NIH HHS NR 30 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 16 BP 5145 EP 5155 DI 10.1093/nar/gki808 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 970AR UT WOS:000232278100020 PM 16155185 ER PT J AU Brown, JL Grau, DJ DeVido, SK Kassis, JA AF Brown, JL Grau, DJ DeVido, SK Kassis, JA TI An Sp1/KLF binding site is important for the activity of a Polycomb group response element from the Drosophila engrailed gene SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BITHORAX COMPLEX; TRANSCRIPTION FACTORS; HOMEOTIC GENE; GAGA FACTOR; CELLULAR MEMORY; PROTEIN COMPLEX; MCP ELEMENT; DNA; SP1; REPRESSION AB Polycomb-group response elements (PREs) are DNA elements through which the Polycomb-group (PcG) of transcriptional repressors act. Many of the PcG proteins are associated with two protein complexes that repress gene expression by modifying chromatin. Both of these protein complexes specifically associate with PREs in vivo, however, it is not known how they are recruited or held at the PRE. PREs are complex elements, made up of binding sites for many proteins. Our laboratory has been working to define all the sequences and DNA binding proteins required for the activity of a 181 bp PRE from the Drosophila engrailed gene. Here we show that one of the sites necessary for PRE activity, Site 2, can be bound by members of the Sp1/KLF family of zinc finger proteins. There are 10 Sp1/KLF family members in Drosophila, and nine of them bind to Site 2. We derive a consensus binding site for the Sp1/KLF Drosophila family members and show that this consensus sequence is present in most of the molecularly characterized PREs. These data suggest that one or more Sp1/KLF family members play a role in PRE function in Drosophila. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Kassis, JA (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM jkassis@mail.nih.gov OI Kassis, Judith/0000-0001-9268-3213 FU Intramural NIH HHS NR 57 TC 46 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 16 BP 5181 EP 5189 DI 10.1039/nar/gki827 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 970AR UT WOS:000232278100023 PM 16155187 ER PT J AU Richards, S Liu, ST Majumdar, A Liu, JL Nairn, RS Bernier, M Maher, V Seidman, MM AF Richards, S Liu, ST Majumdar, A Liu, JL Nairn, RS Bernier, M Maher, V Seidman, MM TI Triplex targeted genomic crosslinks enter separable deletion and base substitution pathways SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; HELIX-FORMING OLIGONUCLEOTIDES; DOUBLE-STRAND BREAKS; HAMSTER OVARY CELLS; TRANSCRIPTION-COUPLED REPAIR; MAMMALIAN-CELLS; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION; GENE KNOCKOUT AB We have synthesized triple helix forming oligonucleotides (TFOs) that target a psoralen (pso) interstrand crosslink to a specific chromosomal site in mammalian cells. Mutagenesis of the targeted crosslinks results in base substitutions and deletions. Identification of the gene products involved in mutation formation is important for developing practical applications of pso-TFOs, and may be informative about the metabolism of other interstrand crosslinks. We have studied mutagenesis of a pso-TFO genomic crosslink in repair proficient and deficient cells. Deficiencies in non homologous end joining and mismatch repair do not influence mutation patterns. In contrast, the frequency of base substitutions is dependent on the activity of ERCC1/XPF and polymerase zeta, but independent of other nucleotide excision repair (NER) or transcription coupled repair (TCR) genes. In NER/TCR deficient cells the frequency of deletions rises, indicating that in wild-type cells NER/TCR functions divert pso-TFO crosslinks from processes that result in deletions. We conclude that targeted pso-TFO crosslinks can enter genetically distinct mutational routes that resolve to base substitutions or deletions. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA. NIA, Clin Invest Lab, Baltimore, MD 21224 USA. Michigan State Univ, Carcinogenesis Lab, E Lansing, MI 48824 USA. RP Seidman, MM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM seidmanm@grc.nia.nih.gov OI Bernier, Michel/0000-0002-5948-368X FU Intramural NIH HHS; NCI NIH HHS [CA097175, P01 CA097175] NR 74 TC 31 Z9 31 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 17 BP 5382 EP 5393 DI 10.1093/nar/gki851 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974LS UT WOS:000232593700011 PM 16186129 ER PT J AU Churbanov, A Rogozin, IB Babenko, VN Ali, H Koonin, EV AF Churbanov, A Rogozin, IB Babenko, VN Ali, H Koonin, EV TI Evolutionary conservation suggests a regulatory function of AUG triplets in 5 '-UTRs of eukaryotic genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID INTERNAL RIBOSOME ENTRY; TRANSLATION INITIATION CODON; VERTEBRATE MESSENGER-RNAS; PROTEIN-CODING SEQUENCES; 5' UNTRANSLATED REGION; OPEN READING FRAMES; SACCHAROMYCES-CEREVISIAE; 5'-UNTRANSLATED REGIONS; MOLECULAR-MECHANISMS; START AB By comparing sequences of human, mouse and rat orthologous genes, we show that in 5'-untranslated regions (5'-UTRs) of mammalian cDNAs but not in 3'-UTRs or coding sequences, AUG is conserved to a significantly greater extent than any of the other 63 nt triplets. This effect is likely to reflect, primarily, bona fide evolutionary conservation, rather than cDNA annotation artifacts, because the excess of conserved upstream AUGs (uAUGs) is seen in 5'-UTRs containing stop codons in-frame with the start AUG and many of the conserved AUGs are found in different frames, consistent with the location in authentic non-coding sequences. Altogether, conserved uAUGs are present in at least 20-30% of mammalian genes. Qualitatively similar results were obtained by comparison of orthologous genes from different species of the yeast genus Saccharomyces. Together with the observation that mammalian and yeast 5'-UTRs are significantly depleted in overall AUG content, these findings suggest that AUG triplets in 5'-UTRs are subject to the pressure of purifying selection in two opposite directions: the uAUGs that have no specific function tend to be deleterious and get eliminated during evolution, whereas those uAUGs that do serve a function are conserved. Most probably, the principal role of the conserved uAUGs is attenuation of translation at the initiation stage, which is often additionally regulated by alternative splicing in the mammalian 5'-UTRs. Consistent with this hypothesis, we found that open reading frames starting from conserved uAUGs are significantly shorter than those starting from non-conserved uAUGs, possibly, owing to selection for optimization of the level of attenuation. C1 Univ Nebraska, Coll Informat Sci & Technol, Dept Comp Sci, Omaha, NE 68182 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Univ Nebraska, Coll Informat Sci & Technol, Dept Comp Sci, Omaha, NE 68182 USA. EM koonin@ncbi.nlm.nih.gov RI Babenko, Vladimir/K-5609-2014; OI Babenko, Vladimir/0000-0002-3077-9559 FU NCRR NIH HHS [P20 RR016469, P20 RR16469] NR 67 TC 61 Z9 66 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 17 BP 5512 EP 5520 DI 10.1093/nar/gki847 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974LS UT WOS:000232593700023 PM 16186132 ER PT J AU Chen, ZH Schneider, TD AF Chen, ZH Schneider, TD TI Information theory based T7-like promoter models: classification of bacteriophages and differential evolution of promoters and their polymerases SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLETE GENOMIC SEQUENCE; COMPLETE NUCLEOTIDE-SEQUENCE; ENTEROCOLITICA SEROTYPE O-3; PSEUDOMONAS-PUTIDA KT2440; K11 RNA-POLYMERASE; MOLECULAR MACHINES; ESCHERICHIA-COLI; CHANNEL CAPACITY; VIRAL COMMUNITY; BINDING-SITES AB Molecular information theory was used to create sequence logos and promoter models for eight phages of the T7 group: T7, phi A1122, T3, phi YeO3-12, SP6, K1-5, gh-1 and K11. When these models were used to scan the corresponding genomes, a significant gap in the individual information distribution was observed between functional promoter sites and other sequences, suggesting that the models can be used to identify new T7-like promoters. When a combined 76-site model was used to scan the eight phages, 108 of the total 109 promoters were found, while none were found for other T7-like phages, phi KMV, P60, VpV262, SIO1, PaP3, Xp10, P-SSP7 and Ppu40, indicating that these phages do not belong to the T7 group. We propose that the T7-like transcription system, which consists of a phage-specific RNA polymerase and a set of conserved T7-like promoters, is a hallmark feature of the T7 group and can be used to classify T7-like phages. Phylogenetic trees of the T7-like promoter models and their corresponding RNA polymerases are similar, suggesting that the eight phages of the T7 group can be classified into five subgroups. However the SP6-like polymerases have apparently diverged from other polymerases more than their promoters have diverged from other promoters. C1 NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. RP Schneider, TD (reprint author), NCI, Ctr Canc Res, Nanobiol Program, POB B, Frederick, MD 21702 USA. EM toms@ncifcrf.gov RI Chen, Zehua/E-6356-2011; chen, zehua/H-1260-2011; OI Schneider, Thomas/0000-0002-9841-1531 FU Intramural NIH HHS NR 90 TC 20 Z9 23 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 19 BP 6172 EP 6187 DI 10.1093/nar/gki915 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 987BR UT WOS:000233493900018 PM 16260472 ER PT J AU Kawano, M Storz, G Rao, BS Rosner, JL Martin, RG AF Kawano, M Storz, G Rao, BS Rosner, JL Martin, RG TI Detection of low-level promoter activity within open reading frame sequences of Escherichia coli SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-POLYMERASE; TRANSCRIPTIONAL ORGANIZATION; COMPARATIVE GENOMICS; TRYPTOPHAN OPERON; INTERNAL PROMOTER; NONCODING RNAS; GENE; ANTISENSE; PROTEIN; IDENTIFICATION AB The search for promoters has largely been confined to sequences upstream of open reading frames (ORFs) or stable RNA genes. Here we used a cloning approach to discover other potential promoters in Escherichia coli. Chromosomal fragments of similar to 160 bp were fused to a promoterless lacZ reporter gene on a multi-copy plasmid. Eight clones were deliberately selected for high activity and 105 clones were selected at random. All eight of the high-activity clones carried promoters that were located upstream of an ORF. Among the randomly-selected clones, 56 had significantly elevated activity. Of these, 7 had inserts which also mapped upstream of an ORF, while 49 mapped within or downstream of ORFs. Surprisingly, the eight promoters selected for high activity matched the canonical sigma(70) -35 and -10 sequences no better than sequences from the randomly-selected clones. For six of the nine most active sequences with orientations opposite to that of the ORF, chromosomal expression was detected by RT-PCR, but defined transcripts were not detected by northern analysis. Our results indicate that the E.coli chromosome carries numerous -35 and -10 sequences with weak promoter activity but that most are not productively expressed because other features needed to enhance promoter activity and transcript stability are absent. C1 NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Natl Lib Med, Natl Biotechnol Ctr, NIH, Bethesda, MD 20892 USA. RP Martin, RG (reprint author), NIDDK, Mol Biol Lab, Bldg 5,Room 333, Bethesda, MD 20892 USA. EM rgmartin@helix.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS NR 39 TC 24 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 19 BP 6268 EP 6276 DI 10.1093/nar/gki928 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 987BR UT WOS:000233493900027 PM 16260475 ER PT J AU Sharma, S Sommers, JA Gary, RK Friedrich-Heineken, E Hubscher, U Brosh, RM AF Sharma, S Sommers, JA Gary, RK Friedrich-Heineken, E Hubscher, U Brosh, RM TI The interaction site of Flap Endonuclease-1 with WRN helicase suggests a coordination of WRN and PCNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID WERNER-SYNDROME PROTEIN; CELL NUCLEAR ANTIGEN; SYNDROME GENE-PRODUCT; DNA-REPLICATION; BLOOMS-SYNDROME; S-PHASE; BIOCHEMICAL-CHARACTERIZATION; RECQ HELICASES; HUMAN FEN1; COMPLEX AB Werner and Bloom syndromes are genetic RecQ helicase disorders characterized by genomic instability. Biochemical and genetic data indicate that an important protein interaction of WRN and Bloom syndrome (BLM) helicases is with the structure-specific nuclease Flap Endonuclease 1 (FEN-1), an enzyme that is implicated in the processing of DNA intermediates that arise during cellular DNA replication, repair and recombination. To acquire a better understanding of the interaction of WRN and BLM with FEN-1, we have mapped the FEN-1 binding site on the two RecQ helicases. Both WRN and BLM bind to the extreme C-terminal 18 amino acid tail of FEN-1 that is adjacent to the PCNA binding site of FEN-1. The importance of the WRN/BLM physical interaction with the FEN-1 C-terminal tail was confirmed by functional interaction studies with catalytically active purified recombinant FEN-1 deletion mutant proteins that lack either the WRN/BLM binding site or the PCNA interaction site. The distinct binding sites of WRN and PCNA and their combined effect on FEN-1 nuclease activity suggest that they may coordinately act with FEN-1. WRN was shown to facilitate FEN-1 binding to its preferred double-flap substrate through its protein interaction with the FEN-1 C-terminal binding site. WRN retained its ability to physically bind and stimulate acetylated FEN-1 cleavage activity to the same extent as unacetylated FEN-1. These studies provide new insights to the interaction of WRN and BLM helicases with FEN-1, and how these interactions might be regulated with the PCNA-FEN-1 interaction during DNA replication and repair. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Nevada, Dept Chem, Las Vegas, NV 89154 USA. Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov RI Gary, Ronald/A-8650-2008; OI Gary, Ronald/0000-0001-5079-1953; Sharma, Sudha/0000-0003-2765-2482 FU Intramural NIH HHS NR 47 TC 32 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 21 BP 6769 EP 6781 DI 10.1093/nar/gki1002 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XI UT WOS:000233990400015 PM 16326861 ER PT J AU Kim, SC Kim, YS Jetten, AM AF Kim, SC Kim, YS Jetten, AM TI Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HEDGEHOG-PATCHED-GLI; SONIC HEDGEHOG; NUCLEAR RECEPTORS; MOUSE DEVELOPMENT; FAMILY; GENE; DOMAIN; DIFFERENTIATION; IDENTIFICATION; ASSOCIATION AB Glis2 is a member of the Gli-similar (Glis) subfamily of Kruppel-like zinc finger transcription factors. It functions as an activator and repressor of gene transcription. To identify potential co-activators or co-repressors that mediate these actions of Glis2, we performed yeast two-hybrid analysis using Glis2 as bait. C-terminal binding protein 1 (CtBP1) was identified as one of the proteins that interact with Glis2. This interaction was confirmed by mammalian two-hybrid analysis. CtBP1 did not interact with other members of the Glis subfamily suggesting that this interaction is specific for Glis2. Pulldown analysis with GST-CtBP1 demonstrated that CtBP1 physically interacts with Glis2. Analysis of CtBP1 and Glis2 deletion mutants identified several regions important for this interaction. CtBP1 repressed transcriptional activation induced by Glis2(1-171). Repression by Glis2 appears to involve the recruitment of both CtBP1 and histone deacetylase 3 (HDAC3). Confocal microscopic analysis demonstrated that Glis2 localized to nuclear speckles while in most cells CtBP1 was found diffusely in both cytoplasm and nucleus. However, when CtBP1 and Glis2 were co-expressed, CtBP1 was restricted to nuclear speckles and co-localized with Glis2. Our observations suggest that the corepressor CtBP1 and HDAC3 are part of transcription silencing complex that mediates the transcriptional repression by Glis2. C1 NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Kim, YS (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. EM kim13@niehs.nih.gov; jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES100485-04] NR 34 TC 21 Z9 26 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 21 BP 6805 EP 6815 DI 10.1093/nar/gki985 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XI UT WOS:000233990400018 PM 16326862 ER PT J AU Renaud, S Loukinov, D Bosman, FT Lobanenkov, V Benhattar, J AF Renaud, S Loukinov, D Bosman, FT Lobanenkov, V Benhattar, J TI CTCF binds the proximal exonic region of hTERT and inhibits its transcription SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TELOMERASE-REVERSE-TRANSCRIPTASE; CATALYTIC SUBUNIT HTERT; C-MYC GENE; TETRAHYMENA TELOMERASE; PROMOTER SEQUENCES; SPLICING PATTERNS; RNA COMPONENT; UP-REGULATION; PROTEIN CTCF; CANCER-CELLS AB The expression of the catalytic subunit (hTERT) represents the limiting factor for telomerase activity. Previously, we detected a transcriptional repressor effect of the proximal exonic region (first two exons) of the hTERT gene. To better understand the mechanism involved and to identify a potential repressor, we further characterized this region. The addition of the hTERT proximal exonic region downstream of the hTERT minimal promoter strongly reduced promoter transcriptional activity in all cells tested (tumor, normal and immortalized). This exonic region also significantly inhibited the transcriptional activity of the CMV and CDKN2A promoters, regardless of the cell type. Therefore, the repressor effect of hTERT exonic region is neither cell nor promoter-dependent. However, the distance between the promoter and the exonic region can modulate this repressor effect, suggesting that nucleosome positioning plays a role in transcriptional repression. We showed by electrophoretic mobility shift assay that CCCTC-binding factor (CTCF) binds to the proximal exonic region of hTERT. Chromatin immunoprecipitaion assays confirmed the binding of CTCF to this region. CTCF is bound to hTERT in cells in which hTERT is not expressed, but not in telomerase-positive ones. Moreover, the transcriptional downregulation of CTCF by RNA interference derepressed hTERT gene expression in normal telomerase-negative cells. Our results suggest that CTCF participates in key cellular mechanisms underlying immortality by regulating hTERT gene expression. C1 CHU Vaudois, Inst Pathol, CH-1011 Lausanne, Switzerland. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Benhattar, J (reprint author), CHU Vaudois, Inst Pathol, Bugnon 25, CH-1011 Lausanne, Switzerland. EM Jean.Benhattar@chuv.hospvd.ch NR 60 TC 65 Z9 68 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 21 BP 6850 EP 6860 DI 10.1093/nar/gki989 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993XI UT WOS:000233990400022 PM 16326864 ER PT J AU Kasprzak, W Bindewald, E Shapiro, BA AF Kasprzak, W Bindewald, E Shapiro, BA TI Structural polymorphism of the HIV-1 leader region explored by computational methods SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PARALLEL GENETIC ALGORITHM; RNA SECONDARY STRUCTURE; PRIMER ACTIVATION SIGNAL; DIMERIZATION INITIATION SITE; IN-VITRO EVIDENCE; REVERSE TRANSCRIPTION; GENOMIC-RNA; STRUCTURE PREDICTION; PACKAGING SIGNAL AB Experimental studies revealed that the elements of the human immunodeficiency virus type 1 (HIV-1) 5'-untranslated leader region (5'-UTR) can fold in vitro into two alternative conformations, branched (BMH) and 'linearized' (LDI) and switch between them to achieve different functionality. In this study we computationally explored in detail, with our massively parallel genetic algorithm (MPGAfold), the propensity of 13 HIV-1 5'-UTRs to fold into the BMH and the LDI conformation types. Besides the BMH conformations these results predict the existence of two functionally equivalent types of LDI conformations. One is similar to what has been shown in vitro to exist in HIV-1 LAI, the other is a novel conformation exemplified by HIV-1 MAL long-distance interactions. These novel MPGAfold results are further corroborated by a consensus probability matrix algorithm applied to a set of 155 HIV-1 sequences. We also have determined in detail the impact of various strain mutations, domain sizes and folds of elongating sequences simulating folding during transcription on HIV-1 RNA secondary structure folding dynamics. C1 NCI Frederick, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI Frederick, Natl Canc Inst, Ctr Canc Res, Nanbiol Program, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI Frederick, SAIC Frederick, Basic Res Program, Bldg 469,Room 150, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 51 TC 21 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 22 BP 7151 EP 7163 DI 10.1093/nar/gki1015 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 000BP UT WOS:000234436200030 PM 16371347 ER PT J AU Barrett, T Suzek, TO Troup, DB Wilhite, SE Ngau, WC Ledoux, P Rudnev, D Lash, AE Fujibuchi, W Edgar, R AF Barrett, T Suzek, TO Troup, DB Wilhite, SE Ngau, WC Ledoux, P Rudnev, D Lash, AE Fujibuchi, W Edgar, R TI NCBI GEO: mining millions of expression profiles - database and tools SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; MICROARRAY DATA; INFORMATION AB The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest fully public repository for high-throughput molecular abundance data, primarily gene expression data. The database has a flexible and open design that allows the submission, storage and retrieval of many data types. These data include microarray-based experiments measuring the abundance of mRNA 5 genomic DNA and protein molecules, as well as nonarray-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. GEO currently holds over 30000 submissions representing approximately half a billion individual molecular abundance measurements, for over 100 organisms. Here, we describe recent database developments that facilitate effective mining and visualization of these data. Features are provided to examine data from both experiment and gene-centric perspectives using user-friendly Web-based interfaces accessible to those without computational or microarray-related analytical expertise. The GEO database is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Edgar, R (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr, Bethesda, MD 20894 USA. EM edgar@ncbi.nlm.nih.gov RI Suzek, Tugba/B-6943-2015 NR 14 TC 503 Z9 537 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D562 EP D566 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300116 PM 15608262 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL AF Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE AB GenBank(C) is a comprehensive database that contains publicly available DNA sequences for more than 165000 named organisms, obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects. Most submissions are made using the web-based Bankit or standalone Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Daily data exchange with the EMBL Data Library in the UK and the DNA Data Bank of Japan helps to ensure worldwide coverage. GenBank is accessible through NCBI's retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, go to the NCBI Homepage at http://www.ncbi.nim.nih.gov. C1 Natl Lib Med, Dept HHS, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), Natl Lib Med, Dept HHS, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov NR 11 TC 488 Z9 511 U1 3 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D34 EP D38 DI 10.1093/nar/gki063 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300006 PM 15608212 ER PT J AU Galperin, MY AF Galperin, MY TI The Molecular Biology Database Collection: 2005 update SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The Nucleic Acids Research Molecular Biology Database Collection is a public online resource that lists the databases described in this and previous issues of Nucleic Acids Research together with other databases of value to the biologist and available throughout the world. All databases included in this Collection are freely available to the public. The 2005 update includes 719 databases, 171 more than the 2004 one. The databases are organized in a hierarchical classification that simplifies the process of finding the right database for any given task. The growing number of databases related to immunology, plant and organelle research have been accommodated by separating them into three new categories. The database summaries provide brief descriptions of the databases, contact details, appropriate references and acknowledgements. The online summaries also serve as a venue for the maintainers of each database to introduce database updates and other improvements in the scope and tools. These updates are particularly important for those databases that have not been described in print in the recent past. The database list and summaries are available online at the Nucleic Acids Research web site, http://nar.oupjournals.org/. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 11 TC 37 Z9 42 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D5 EP D24 DI 10.1093/nar/gki139 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300003 PM 15608247 ER PT J AU Maglott, D Ostell, J Pruitt, KD Tatusova, T AF Maglott, D Ostell, J Pruitt, KD Tatusova, T TI Entrez Gene: gene-centered information at NCBI SO NUCLEIC ACIDS RESEARCH LA English DT Article AB Entrez Gene (www.ncbi.nim.nih.gov/entrez/query. fcgi?db=gene) is NCBI's database for gene-specific information. It does not include all known or predicted genes; instead Entrez Gene focuses on the genomes that have been completely sequenced, that have an active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is updated as new information becomes available. Entrez Gene is a step forward from NCBI's LocusLink, with both a major increase in taxonomic scope and improved access through the many tools associated with NCBI Entrez. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Maglott, D (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Room 5AS,13B,45 Ctr Dr, Bethesda, MD 20892 USA. EM maglott@ncbi.nlm.nih.gov NR 5 TC 447 Z9 475 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D54 EP D58 DI 10.1093/nar/gki031 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300009 PM 15608257 ER PT J AU Marchler-Bauer, A Anderson, JB Cherukuri, PF DeWweese-Scott, C Geer, LY Gwadz, M He, SQ Hurwitz, DI Jackson, JD Ke, ZX Lanczycki, CJ Liebert, CA Liu, CL Lu, F Marchler, GH Mullokandov, M Shoemaker, BA Simonyan, V Song, JS Thiessen, PA Yamashita, RA Yin, JJ Zhang, DC Bryant, SH AF Marchler-Bauer, A Anderson, JB Cherukuri, PF DeWweese-Scott, C Geer, LY Gwadz, M He, SQ Hurwitz, DI Jackson, JD Ke, ZX Lanczycki, CJ Liebert, CA Liu, CL Lu, F Marchler, GH Mullokandov, M Shoemaker, BA Simonyan, V Song, JS Thiessen, PA Yamashita, RA Yin, JJ Zhang, DC Bryant, SH TI CDD: a conserved domain database for protein classification SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALIGNMENTS; SEQUENCE AB The Conserved Domain Database (CDD) is the protein classification component of NCBI's Entrez query and retrieval system. CDD is linked to other Entrez databases such as Proteins, Taxonomy and PubMed(R), and can be accessed at http://www.ncbi.nlm.nih. gov/entrez/query.fcgi?db=cdd. CD-Search, which is available at http://www.ncbi.nim.nih.gov/Structure/ cdd/wrpsb.cgi, is a fast, interactive tool to identify conserved domains in new protein sequences. CD-Search results for protein sequences in Entrez are pre-computed to provide links between proteins and domain models, and computational annotation visible upon request. Protein-protein queries submitted to NCBI's BLAST search service at http:// www.ncbi.nim.nih.gov/BLAST are scanned for the presence of conserved domains by default. While CDD started out as essentially a mirror of publicly available domain alignment collections, such as SMART, Pfam and COG, we have continued an effort to update, and in some cases replace these models with domain hierarchies curated at the NCBI. Here, we report on the progress of the curation effort and associated improvements in the functionality of the CDD information retrieval system. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bldg 38A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM bauer@ncbi.nlm.nih.gov RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 9 TC 589 Z9 625 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D192 EP D196 DI 10.1093/nar/gki069 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300037 PM 15608175 ER PT J AU Pruitt, KD Tatusova, T Maglott, DR AF Pruitt, KD Tatusova, T Maglott, DR TI NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENERATION AB The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database (http://www.ncbi.nim.nih.gov/RefSeq/) provides a non-redundant collection of sequences representing genomic data, transcripts and proteins. Although the goal is to provide a comprehensive dataset representing the complete sequence information for any given species, the database pragmatically includes sequence data that are currently publicly available in the archival databases. The database incorporates data from over 2400 organisms and includes over one million proteins representing significant taxonomic diversity spanning prokaryotes, eukaryotes and viruses. Nucleotide and protein sequences are explicitly linked, and the sequences are linked to other resources including the NCBI Map Viewer and Gene. Sequences are annotated to include coding regions, conserved domains, variation, references, names, database cross-references, and other features using a combined approach of collaboration and other input from the scientific community, automated annotation, propagation from GenBank and curation by NCBI staff. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Rm 6An 12J,45 Ctr Dr, Bethesda, MD 20892 USA. EM pruitt@ncbi.nlm.nih.gov NR 14 TC 714 Z9 747 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D501 EP D504 DI 10.1093/nar/gki025 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300103 PM 15608248 ER PT J AU Wheeler, DL Barrett, T Benson, DA Bryant, SH Canese, K Church, DM Di Cuccio, M Edgar, R Federhen, S Helmberg, W Kenton, DL Khovayko, O Lipman, DJ Madden, TL Maglott, DR Ostell, J Pontius, JU Pruitt, KD Schuler, GD Schriml, LM Sequeira, E Sherry, ST Sirotkin, K Starchenko, G Suzek, TO Tatusov, R Tatusova, TA Wagner, L Yaschenko, E AF Wheeler, DL Barrett, T Benson, DA Bryant, SH Canese, K Church, DM Di Cuccio, M Edgar, R Federhen, S Helmberg, W Kenton, DL Khovayko, O Lipman, DJ Madden, TL Maglott, DR Ostell, J Pontius, JU Pruitt, KD Schuler, GD Schriml, LM Sequeira, E Sherry, ST Sirotkin, K Starchenko, G Suzek, TO Tatusov, R Tatusova, TA Wagner, L Yaschenko, E TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PSI-BLAST; PROTEIN; SEARCH; ENTREZ; SEQUENCES; TOOL AB In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data retrieval systems and computational resources for the analysis of data in GenBank and other biological data made available through NCBI's website. NCBI resources include Entrez, Entrez Programming Utilities, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups (COGs), Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus (GEO), Online Mendelian Inheritance in Man (OMIM), the Molecular Modeling Database (MMDB), the Conserved Domain Database (CDD) and the Conserved Domain Architecture Retrieval Tool (CDART). Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized datasets. All of the resources can be accessed through the NCBI home page at http://www.ncbi.nim.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov RI Suzek, Tugba/B-6943-2015; OI Suzek, Tugba/0000-0002-3243-1759; Schriml, Lynn/0000-0001-8910-9851 NR 28 TC 285 Z9 299 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2005 VL 33 SI SI BP D39 EP D45 DI 10.1093/nar/gki062 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 890PW UT WOS:000226524300007 PM 15608222 ER PT J AU Coumoul, X Shukla, V Li, CL Wang, RH Deng, CX AF Coumoul, X Shukla, V Li, CL Wang, RH Deng, CX TI Conditional knockdown of Fgfr2in mice using Cre-LoxP induced RNA interference SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMALIAN-CELLS; TUMOR-FORMATION; KNOCKOUT MICE; MOUSE; GENE; RECOMBINASE; EXPRESSION; BRCA1; MORPHOGENESIS; DISRUPTION AB RNA interference (RNAi)-mediated gene knockdown is a potent approach for studying gene function. We have previously reported a plasmid-based, tamoxifen-inducible gene knockdown system in cultured cells using a combined RNAi and Cre-LoxP system. Here, we validate this system in mouse and show that it can be used to suppress the expression of an endogenous gene (Fgfr2) with high efficiency. We show that transgenic mice carrying the U6-ploxPneo-Fgfr2 RNAi construct are normal, displaying Fgfr2 transcripts equivalent to those of wild-type controls, indicating that the U6 promoter is inactive in vivo due to the presence of the neo in the promoter. After excision of the neo by crossing with transgenic mice that express Cre in the mouse germline, the U6 promoter is activated, leading to over 95% reduction of Fgfr2 transcripts, and consequently, embryonic lethality. On the other hand, activation of the U6 promoter using transgenic mice that express Cre in the progress zone of the limb results in live mice with malformation of digits of both the forelimbs and hindlimbs. This method provides a fast, yet efficient way to decipher gene functions in vivo in a tissue-specific manner. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 39 TC 68 Z9 74 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 11 AR E102 DI 10.1093/nar/gni100 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943ID UT WOS:000230345800006 PM 15987787 ER PT J AU Ebersole, T Okamoto, Y Noskov, VN Kouprina, N Kim, JH Leem, SH Barrett, JC Masumoto, H Larionov, V AF Ebersole, T Okamoto, Y Noskov, VN Kouprina, N Kim, JH Leem, SH Barrett, JC Masumoto, H Larionov, V TI Rapid generation of long synthetic tandem repeats and its application for analysis in human artificial chromosome formation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ALPHA-SATELLITE DNA; TRANSFORMATION-ASSOCIATED RECOMBINATION; ROLLING CIRCLE AMPLIFICATION; CENP-B BOX; HUMAN CENTROMERE; SEQUENCE; CELLS; CONSTRUCTION; CHROMATIN; GENE AB Human artificial chromosomes (HACs) provide a unique opportunity to study kinetochore formation and to develop a new generation of vectors with potential in gene therapy. An investigation into the structural and the functional relationship in centromeric tandem repeats in HACs requires the ability to manipulate repeat substructure efficiently. We describe here a new method to rapidly amplify human alphoid tandem repeats of a few hundred base pairs into long DNA arrays up to 120 kb. The method includes rolling-circle amplification (RCA) of repeats in vitro and assembly of the RCA products by in vivo recombination in yeast. The synthetic arrays are competent in HAC formation when transformed into human cells. As short multimers can be easily modified before amplification, this new technique can identify repeat monomer regions critical for kinetochore seeding. The method may have more general application in elucidating the role of other tandem repeats in chromosome organization and dynamics. C1 Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Larionov, V (reprint author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. EM larionov@mail.nih.gov FU Intramural NIH HHS NR 41 TC 24 Z9 25 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 15 AR e130 DI 10.1093/nar/gni129 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 965BT UT WOS:000231925700002 PM 16141190 ER PT J AU He, LS Wu, XL Simone, J Hewgill, D Lipsky, PE AF He, LS Wu, XL Simone, J Hewgill, D Lipsky, PE TI Determination of tumor necrosis factor receptor-associated factor trimerization in living cells by CFP -> YFP -> mRFP FRET detected by flow cytometry SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RESONANCE ENERGY-TRANSFER; GREEN FLUORESCENT PROTEIN; INDUCED APOPTOSIS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; SINGLE-LASER; MICROSCOPY; OLIGOMERIZATION; ACTIVATION; DYNAMICS AB The availability of protein fluorophores with appropriate spectral properties has made it possible to employ fluorescence resonance energy transfer (FRET) to assess interactions between three proteins microscopically. Flow cytometry offers excellent sensitivity, effective signal separation and the capacity to assess a large number of events, and, therefore, should be an ideal means to explore protein interactions in living cells. Here, we report a flow-cytometric FRET technique that employed both direct energy transfer from CFP -> YFP -> mRFP and donor quenching to assess TRAF2 trimerization in living cells. Initially, a series of fusion proteins incorporating CFP, YFP and mRFP with spacers that did or did not permit FRET were employed to document the magnitude of CFP -> YFP and YFP -> mRFP FRET and to calculate the efficiency of CFP -> YFP -> mRFP two-step FRET. Based upon this, TRAF2 homotrimerization could be detected. This method should have great utility in studying the dynamics of interactions between three specific proteins in vivo. C1 Natl Inst Arthritis & Musculoskeletal & Skin Dis, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. Natl Inst Arthritis & Musculoskeletal & Skin Dis, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP He, LS (reprint author), Natl Inst Arthritis & Musculoskeletal & Skin Dis, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. EM Lihe@mail.nih.gov NR 22 TC 32 Z9 33 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 6 AR e61 DI 10.1093/nar/gni057 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916PR UT WOS:000228398400009 PM 15805120 ER PT J AU Lewis, SM Chen, SA Strathern, JN Rattray, AJ AF Lewis, SM Chen, SA Strathern, JN Rattray, AJ TI New approaches to the analysis of palindromic sequences from the human genome: evolution and polymorphism of an intronic site at the NF1 locus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; AT-RICH PALINDROMES; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; DNA PALINDROMES; NEUROFIBROMATOSIS TYPE-1; CRUCIFORM STRUCTURES; GENE AMPLIFICATION; INVERTED REPEATS; SHADOW BANDS AB The nature of any long palindrome that might exist in the human genome is obscured by the instability of such sequences once cloned in Escherichia coli. We describe and validate a practical alternative to the analysis of naturally-occurring palindromes based upon cloning and propagation in Saccharomyces cerevisiae. With this approach we have investigated an intronic sequence in the human Neurofibromatosis 1 (NF1) locus that is represented by multiple conflicting versions in GenBank. We find that the site is highly polymorphic, exhibiting different degrees of palindromy in different individuals. A side-by-side comparison of the same plasmids in E.coli versus. S.cerevisiae demonstrated that the more palindromic alleles were inevitably corrupted upon cloning in E.coli, but could be propagated intact in yeast. The high quality sequence obtained from the yeast-based approach provides insight into the various mechanisms that destabilize a palindrome in E.coli, yeast and humans, into the diversification of a highly polymorphic site within the NF1 locus during primate evolution, and into the association between palindromy and chromosomal translocation. C1 Hosp Sick Children, Res Inst, Program Genet & Genom Biol, Toronto, ON M5G 1L7, Canada. Univ Toronto, Grad Dept Mol & Med Genet, Toronto, ON, Canada. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21701 USA. RP Lewis, SM (reprint author), Hosp Sick Children, Res Inst, Program Genet & Genom Biol, TMDT Bldg,E Tower Rm 15-308,101 Coll St, Toronto, ON M5G 1L7, Canada. EM susanna@sickkids.ca RI Rattray, Alison/A-4847-2008 FU Intramural NIH HHS NR 56 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 22 AR e186 DI 10.1093/nar/gni189 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 000BP UT WOS:000234436200001 PM 16340004 ER PT J AU Takahashi, N Dawid, IB AF Takahashi, N Dawid, IB TI Characterizationof zebrafish Rad52 and replication protein A for oligonucleotide-mediated mutagenesis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; TARGETED GENE CORRECTION; SYNTHETIC OLIGONUCLEOTIDES; SACCHAROMYCES-CEREVISIAE; POLYMERASE-DELTA; CHIMERIC RNA/DNA; IN-VIVO; REPAIR; YEAST; CELLS AB Zebrafish has become a favorite model organism not only in genetics and developmental biology, but also for the study of cancer, neuroscience and metabolism. However, strategies for reverse genetics in zebrafish are mostly limited to the use of antisense oligonucleotides, and therefore the development of other targeting methods is highly desirable. Here, we report an approach to gene targeting in this system in which single-stranded oligonucleotides and zebrafish Rad52 protein are employed. It has been proposed that a single-stranded oligonucleotide containing a mutation can be incorporated into the genome by annealing to the single-stranded region of the lagging strand of the replication fork. Rad52 is expected to accelerate the annealing step. In vitro experiments using purified truncated Rad52 proteins and replication protein A (RPA) showed that annealing of oligonucleotides is accelerated by Rad52 in the presence of RPA. We developed a simple and sensitive PCR-based method to detect point mutations in the genome. In exploratory experiments, we found that microinjection of single-stranded oligonucleotide targeted to a specific gene together with truncated Rad52 into zebrafish embryos resulted in a low level of recombinant copies in 3 of the 80 embryos tested under these conditions. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@mail.nih.gov FU Intramural NIH HHS NR 39 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 13 AR e120 DI 10.1093/nar/gni122 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 959KP UT WOS:000231516900050 PM 16061934 ER PT J AU Thompson, KL Rosenzweig, BA Pine, PS Retief, J Turpaz, Y Afshari, CA Hamadeh, HK Damore, MA Boedigheimer, M Blomme, E Ciurlionis, R Waring, JF Fuscoe, JC Paules, R Tucker, CJ Fare, T Coffey, EM He, Y Collins, PJ Jarnagin, K Fujimoto, S Ganter, B Kiser, G Kaysser-Kranich, T Sina, J Sistare, FD AF Thompson, KL Rosenzweig, BA Pine, PS Retief, J Turpaz, Y Afshari, CA Hamadeh, HK Damore, MA Boedigheimer, M Blomme, E Ciurlionis, R Waring, JF Fuscoe, JC Paules, R Tucker, CJ Fare, T Coffey, EM He, Y Collins, PJ Jarnagin, K Fujimoto, S Ganter, B Kiser, G Kaysser-Kranich, T Sina, J Sistare, FD TI Use of a mixed tissue RNA design for performance assessments on multiple microarray formats SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE MICROARRAYS; ARRAYS; PLATFORMS; ACCURACY; DATABASE; NOISE AB The comparability and reliability of data generated using microarray technology would be enhanced by use of a common set of standards that allow accuracy, reproducibility and dynamic range assessments on multiple formats. We designed and tested a complex biological reagent for performance measurements on three commercial oligonucleotide array formats that differ in probe design and signal measurement methodology. The reagent is a set of two mixtures with different proportions of RNA for each of four rat tissues (brain, liver, kidney and testes). The design provides four known ratio measurements of > 200 reference probes, which were chosen for their tissue-selectivity, dynamic range coverage and alignment to the same exemplar transcript sequence across all three platforms. The data generated from testing three biological replicates of the reagent at eight laboratories on three array formats provides a benchmark set for both laboratory and data processing performance assessments. Close agreement with target ratios adjusted for sample complexity was achieved on all platforms and low variance was observed among platforms, replicates and sites. The mixed tissue design produces a reagent with known gene expression changes within a complex sample and can serve as a paradigm for performance standards for microarrays that target other species. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Abbott Labs, Abbott Pk, IL 60064 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Rosetta Inpharmat LLC, Seattle, WA 98109 USA. Agilent Technol, Palo Alto, CA 94304 USA. Iconix Pharmaceut Inc, Mountain View, CA 94043 USA. GE Healthcare, Chandler, AZ 85248 USA. Merck & Co Inc, West Point, PA 19486 USA. RP Thompson, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, White Oak Life Sci Bldg 64,10903 New Hampshire Av, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov RI Kiser, Gretchen/A-3228-2013 NR 27 TC 20 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 22 AR e187 DI 10.1093/nar/gni186 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 000BP UT WOS:000234436200002 PM 16377776 ER PT J AU Warming, S Costantino, N Court, DL Jenkins, NA Copeland, NG AF Warming, S Costantino, N Court, DL Jenkins, NA Copeland, NG TI Simple and highly efficient BAC recombineering using gaIK selection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOMES; ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; DNA; OLIGONUCLEOTIDES; VECTORS; MUTANTS; REGION; RESCUE; SYSTEM AB Recombineering allows DNA cloned in Escherichia coli to be modified via lambda (lambda) Red-mediated homologous recombination, obviating the need for restriction enzymes and DNA ligases to modify DNA. Here, we describe the construction of three new recombineering strains (SW102, SW105 and SW106) that allow bacterial artificial chromosomes (BACs) to be modified using galK positive/negative selection. This two-step selection procedure allows DNA to be modified without introducing an unwanted selectable marker at the modification site. All three strains contain an otherwise complete galactose operon, except for a precise deletion of the galK gene, and a defective temperature-sensitive lambda prophage that makes recombineering possible. SW105 and SW106 cells in addition carry L-arabinose-inducible Cre or Flp genes, respectively. The galK function can be selected both for and against. This feature greatly reduces the background seen in other negative-selection schemes, and galK selection is considerably more efficient than other related selection methods published. We also show how galK selection can be used to rapidly introduce point mutations, deletions and IoxP sites into BAC DNA and thus facilitate functional studies of SNP and/or disease-causing point mutations, the identification of long-range regulatory elements and the construction of conditional targeting vectors. C1 NCI, Mouse Canc Genet Program, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Gene Regulat & chromosome Biol Lab, Frederick, MD 21702 USA. RP Copeland, NG (reprint author), NCI, Mouse Canc Genet Program, Canc Res Ctr, W 7th St,Bldg 539,POB B, Frederick, MD 21702 USA. EM Copeland@ncifcrf.gov NR 21 TC 618 Z9 625 U1 5 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 4 AR e36 DI 10.1093/nar/gni035 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905JW UT WOS:000227565400003 PM 15731329 ER PT J AU Marquez, VE Barchi, JJ Kelley, JA Rao, KVR Agbaria, R Ben-Kasus, T Cheng, JC Yoo, CB Jones, PA AF Marquez, VE Barchi, JJ Kelley, JA Rao, KVR Agbaria, R Ben-Kasus, T Cheng, JC Yoo, CB Jones, PA TI Zebularine: A unique molecule for an epigenetically based strategy in cancer chemotherapy. The magic of its chemistry and biology SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 16th International Roundtable of the International-Society-for-Nucleosides-Nucleotides-and-Nucleic-Acids (IS3NA) CY SEP 12-16, 2004 CL Univ Minnesota, Ctr Drug Design, Minneapolis, MN SP Int Soc Nucleosides, Nucleotides & Nucle Acids, Alnylam US Inc, TriLink BioTechnologies, Austin Chem, Berry & Associates Inc, Gilead, Glen Res Corp, Anadys Pharmaceut Inc, GlaxoSmithKline, Indenix HO Univ Minnesota, Ctr Drug Design DE zebularine; ring-expanded nucleoside analogues; isouridine; cytidine deaminase inhibition; DNA methyltrasferase inhibition; antitumor activity ID NUCLEIC-ACID COMPONENTS; DNA METHYLATION INHIBITOR; CYTIDINE DEAMINASE; 2-PYRIMIDINONE NUCLEOSIDES; RIBOSIDE ZEBULARINE; ANALOGS; ENZYME; 5-AZA-2'-DEOXYCYTIDINE; METHYLTRANSFERASE; CYTOSINE AB 1-(beta-(D)-ribofuranosyl)- 1,2-dihydropyrimidin-2-one (zebularine) is structurally 4-deamino cytidine. The increased electraphilic character of this simple aglycon endows the molecule with unique chemical and biological properties, making zebularine a versatile starting material for the synthesis of complex nucleosides and an effective inhibitor of cytidine deaminase and DNA cytosine methyltransferase. Zebularine is a stable, antitumor agent that preferentially targets cancer cells and shows activity both in vitro and in experimental animals, even after oral administration. C1 NCI, Ctr Canc Res, Med Chem Lab, NIH, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Dept Clin Pharmacol, Fac Hlth Sci, IL-84105 Beer Sheva, Israel. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Urol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA USA. RP Marquez, VE (reprint author), NCI, Ctr Canc Res, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 32 TC 28 Z9 29 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2005 VL 24 IS 5-7 SI SI BP 305 EP 318 DI 10.1081/NCN-200059765 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972SM UT WOS:000232473500001 PM 16247946 ER PT J AU Lee, HW Shin, DH Jeong, JY Kim, HO Chun, MW Melman, N Gao, ZG Jacobson, KA Jeong, LS AF Lee, HW Shin, DH Jeong, JY Kim, HO Chun, MW Melman, N Gao, ZG Jacobson, KA Jeong, LS TI D-4 '-thioadenosine derivatives as highly potent and selective agonists at the human A(3) adenosine receptor SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 16th International Roundtable of the International-Society-for-Nucleosides-Nucleotides-and-Nucleic-Acids (IS3NA) CY SEP 12-16, 2004 CL Univ Minnesota, Ctr Drug Design, Minneapolis, MN SP Int Soc Nucleosides, Nucleotides & Nucle Acids, Alnylam US Inc, TriLink BioTechnologies, Austin Chem, Berry & Associates Inc, Gilead, Glen Res Corp, Anadys Pharmaceut Inc, GlaxoSmithKline, Indenix HO Univ Minnesota, Ctr Drug Design AB 4'-Thionucleoside derivatives as potent and selective A(3) adenosine receptor agonists were synthesized, starting from D-gulono-gamma-lactone via D-thioribosyl acetate as a key intermediate, among which the 2-chloro-N-6-methyladenosine-5'-methyluronamide showed the most potent and selective binding affinity (K-i = 0.28 +/- 0.09 nM) at the human A(3) adenosine receptor. C1 Ewha Womans Univ, Med Chem Lab, Coll Pharm, Seoul 120750, South Korea. NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Pharm, Seoul, South Korea. RP Lee, HW (reprint author), Ewha Womans Univ, Med Chem Lab, Coll Pharm, Seoul 120750, South Korea. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 3 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2005 VL 24 IS 5-7 SI SI BP 607 EP 609 DI 10.1081/NCN-200061827 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972SM UT WOS:000232473500052 PM 16247997 ER PT J AU Maderia, M Wu, J Bax, A Shenoy, S O'Keefe, B Marquez, VE Barchi, JJ AF Maderia, M Wu, J Bax, A Shenoy, S O'Keefe, B Marquez, VE Barchi, JJ TI Engineering DNA topology with locked nucleosides: A structural study SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 16th International Roundtable of the International-Society-for-Nucleosides-Nucleotides-and-Nucleic-Acids (IS3NA) CY SEP 12-16, 2004 CL Univ Minnesota, Ctr Drug Design, Minneapolis, MN SP Int Soc Nucleosides, Nucleotides & Nucle Acids, Alnylam US Inc, TriLink BioTechnologies, Austin Chem, Berry & Associates Inc, Gilead, Glen Res Corp, Anadys Pharmaceut Inc, GlaxoSmithKline, Indenix HO Univ Minnesota, Ctr Drug Design AB DNA dodecamers modified with nucleotide building blocks based on a bicyclo[3.1.0]hexane system that effectively locks the ribose template into an RNA-like or North (N) conformation were analyzed by various biophysical techniques including high field nuclear magnetic resonance (NMR). Replacement of either one or both of the center thymidines in the Dickerson Drew dodecamer (CGCGAAT*T*CGCG) caused a progressive shift in the bending propensity of the double helix as shown by a newly developed rapid technique that compares the residual dipolar coupling (RDC) values of the modified duplexes with those previously determined for the native DNA. C1 NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. NCI, Lab Drug Discovery Res, Ctr Canc Res, Frederick, MD 21702 USA. RP Barchi, JJ (reprint author), NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 6 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2005 VL 24 IS 5-7 SI SI BP 687 EP 690 DI 10.1081/NCN-200060256 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972SM UT WOS:000232473500070 PM 16248015 ER PT J AU Sun, GY Voigt, JH Marquez, VE Nicklaus, MC AF Sun, GY Voigt, JH Marquez, VE Nicklaus, MC TI PROSIT, an online service to calculate pseudorotational parameters of nucleosides and nucleotides SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 16th International Roundtable of the International-Society-for-Nucleosides-Nucleotides-and-Nucleic-Acids (IS3NA) CY SEP 12-16, 2004 CL Univ Minnesota, Ctr Drug Design, Minneapolis, MN SP Int Soc Nucleosides, Nucleotides & Nucle Acids, Alnylam US Inc, TriLink BioTechnologies, Austin Chem, Berry & Associates Inc, Gilead, Glen Res Corp, Anadys Pharmaceut Inc, GlaxoSmithKline, Indenix HO Univ Minnesota, Ctr Drug Design ID SUGAR RING; DISCRIMINATE; PUCKER AB The online service PROSIT (Pseudo-Rotational Online Service and Interactive Tool) is a free service available at http://cactus.nci.nih.gov/prosit/ that performs pseudorotational analysis of nucleosides(tides). PROSIT reads the 3D coordinates of nucleosides and returns the pseudorotational phase angle P, puckering amplitude nu(max) and other related information. As examples the sugar conformations in a parallel-stranded guanine tetraplex and a four-way Holliday junction are presented here. C1 NCI, Med Chem Lab, CCR, NIH,DHHS, Frederick, MD 21702 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, CCR, NIH,DHHS, 376 Boyles Dt, Frederick, MD 21702 USA. EM marquezv@mail.nih.gov OI Nicklaus, Marc/0000-0002-4775-7030 NR 11 TC 5 Z9 5 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2005 VL 24 IS 5-7 SI SI BP 1029 EP 1032 DI 10.1081/NCN-200059757 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972SM UT WOS:000232473500141 PM 16248085 ER PT J AU Chun, MW Lee, HW Kim, AY Kim, MJ Kim, HO Gao, ZG Jacobson, KA Jeong, LS AF Chun, MW Lee, HW Kim, AY Kim, MJ Kim, HO Gao, ZG Jacobson, KA Jeong, LS TI Synthesis of 3 '-ureidoadenosine analogues and their binding affinity to the A(3) adenosine receptor SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article; Proceedings Paper CT 16th International Roundtable of the International-Society-for-Nucleosides-Nucleotides-and-Nucleic-Acids (IS3NA) CY SEP 12-16, 2004 CL Univ Minnesota, Ctr Drug Design, Minneapolis, MN SP Int Soc Nucleosides, Nucleotides & Nucle Acids, Alnylam US Inc, TriLink BioTechnologies, Austin Chem, Berry & Associates Inc, Gilead, Glen Res Corp, Anadys Pharmaceut Inc, GlaxoSmithKline, Indenix HO Univ Minnesota, Ctr Drug Design ID SELECTIVITY; DESIGN AB Novel 3'-ureidoadenosine analogues were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose in order to lead to stronger hydrogen bonding at the A(3) adenosine receptor than the corresponding 3'-aminoadenosine derivatives. However, all synthesized 3'-ureidoadenosine analogues have lost their binding affinities to the all subtypes of adenosine receptors, indicating that bulky 3'-urea moiety led to conformational distortion. C1 Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Chun, MW (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 5 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2005 VL 24 IS 5-7 SI SI BP 1119 EP 1121 DI 10.1081/NCN-200060079 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972SM UT WOS:000232473500160 PM 16248104 ER PT J AU Duong, HT Gao, ZG Jacobson, KA AF Duong, HT Gao, ZG Jacobson, KA TI Nucleoside modification and concerted mutagenesis of the human A(3) adenosine receptor to probe interactions between the 2-position of adenosine analogs and Gln(167) in the second extracellular loop SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE G protein-coupled receptor; purines; neoceptor; mutagenesis; extra-cellular loop ID 2ND EXTRACELLULAR LOOP; LIGAND RECOGNITION; A(3) RECEPTOR; ACTIVATION; EFFICACY; AFFINITY; DERIVATIVES; INHIBITION; RESIDUES; AGONISTS AB Residues of the second extracellular loop are believed to be important for ligand recognition in adenosine receptors. Molecular modeling studies have suggested that one such residue, Gln(167) of the human A(3) receptor, is in proximity to the C2 moiety of some adenosine analogs when bound. Here this putative interaction was systematically explored using a neoceptor strategy, i.e., by site-directed mutagenesis and examination of the affinities of nucleosides modified to have complementary functionality. Gln(167) was mutated to Ala, Glu, and Arg, while the 2-position of several adenosine analogs was substituted with amine or carboxylic acid groups. All compounds tested lost affinity to the mutant receptors in comparison to the wild type. However, comparing affinities among the mutant receptors, several compounds bearing charge at the 2-position demonstrated preferential affinity for the mutant receptor bearing a residue of complementary charge. 13, with a positively-charged C2 moiety, displayed an 8.5-fold increase in affinity at the Q167E mutant receptor versus the Q167R mutant receptor. Preferential affinity for specific mutant receptors was also observed for 8 and 12. The data suggests that a direct contact is made between the C2 substituent of some charged ligands and the mutant receptor bearing the opposite charge at position 167. C1 NIDDK, LBC, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP NIDDK, LBC, Mol Recognit Sect, NIH, Bldg 8A Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS NR 21 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1525-7770 EI 1532-2335 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2005 VL 24 IS 10-12 BP 1507 EP 1517 DI 10.1080/15257770500265778 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 994WC UT WOS:000234060900008 PM 16438031 ER PT J AU Chang, S Erdman, JW Clinton, SK Vadiveloo, M Strom, SS Yamamura, Y Duphorne, CM Spitz, MR Amos, CI Contois, JH Gu, X Babaian, RJ Scardino, PT Hursting, SD AF Chang, S Erdman, JW Clinton, SK Vadiveloo, M Strom, SS Yamamura, Y Duphorne, CM Spitz, MR Amos, CI Contois, JH Gu, X Babaian, RJ Scardino, PT Hursting, SD TI Relationship between plasma carotenoids and prostate cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FOLLOW-UP; LYCOPENE; SERUM; RETINOL; RISK; HEALTH; MICRONUTRIENTS; METABOLISM; BIOMARKERS; TOCOPHEROL AB Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, beta-cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta-carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of >= 7, n=88) vs. less aggressive cases (Gleason scores of < 7, n=30)failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of beta-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Unit 1365, Houston, TX 77030 USA. Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA. Ohio State Univ, Coll Med, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA. NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Chang, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Unit 1365, 1155 Herman P Pressler Canc Prevent Bldg,Rm 7-355, Houston, TX 77030 USA. EM shinechang@MDAnderson.org FU NCI NIH HHS [CA 57730, CA 68578, CA58204] NR 31 TC 26 Z9 26 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2005 VL 53 IS 2 BP 127 EP 134 DI 10.1207/s15327914nc5302_1 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 041DL UT WOS:000237433400001 PM 16573373 ER PT J AU Thomson, CA Giuliano, AR Shaw, JW Rock, CL Ritenbaugh, CK Hakim, IA Hollenbach, KA Alberts, DS Pierce, JP AF Thomson, CA Giuliano, AR Shaw, JW Rock, CL Ritenbaugh, CK Hakim, IA Hollenbach, KA Alberts, DS Pierce, JP TI Diet and biomarkers of oxidative damage in women previously treated for breast cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID ENVIRONMENTAL TOBACCO-SMOKE; DNA-DAMAGE; VITAMIN-E; BLOOD-CELLS; ELDERLY POPULATION; HUMAN INTERVENTION; URINARY-EXCRETION; RANDOMIZED TRIAL; OXYGEN RADICALS; STRESS AB This study sought to evaluate the relationship between dietary intake of fat, polyunsaturated fat, saturated fat, arachidonic acid, and selected dietary antioxidants and levels of oxidative damage as measured by urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epi-prostaglandin F2 alpha (8-iso-PGF2 alpha) in women previously treated for breast cancer Two hundred two study subjects participating in the Women's Healthy Eating and Living (WHEL) study were included in this ancillary study. Dietary intakes and concentrations of urinary 8-OHdG and 8-iso-PGF2a were measured at baseline and 12 mo in the 179 women included in the analytical cohort. Study subjects demonstrated a significant reduction in dietary total, polyunsaturated, and saturated fat intake and a significant increase in vitamins E and C and beta-carotene intake from baseline to 12 mo. Linear mixed-models analysis using baseline and Year 1 data indicated that vitamin E intake was inversely associated with both 8-OHdG and 8-iso-PM alpha. 8-Iso-PGF2 alpha is increased with increased body mass index (BMI) and polyunsaturated fatty acid (PUFA) intake, indicating an increase in lipid peroxidation with greater BMI and higher PUFA intake. 8-OHdG was inversely related to age but positively related to arachidonic acid, indicating an increase in DNA damage with higher intake of arachidonic acid (meat). The results of this nested case-controlled study provide potential mechanisms by which a high fruit and vegetable, low-fat diet might reduce the recurrence rate of or early-stage breast cancer. C1 Univ Arizona, Dept Nutr Sci, Tucson, AZ 85721 USA. Univ Arizona, Arizona Canc Ctr, Canc Prevent & Control, Tucson, AZ 85721 USA. Univ Arizona, Coll Publ Hlth, Tucson, AZ 85724 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA. NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Bethesda, MD 20892 USA. Univ Calif San Diego, Rebecca & John Moores Canc Ctr, Canc Prevent & Control Program, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Univ Arizona, Coll Med, Dept Family & Community Med, Tucson, AZ 85724 USA. RP Thomson, CA (reprint author), Univ Arizona, Dept Nutr Sci, Tucson, AZ 85721 USA. EM cthomson@email.arizona.edu FU NCI NIH HHS [CA-23074, CA-69375-02] NR 77 TC 18 Z9 18 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2005 VL 51 IS 2 BP 146 EP 154 DI 10.1207/s15327914nc5102_4 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 926XR UT WOS:000229157500004 PM 15860436 ER PT J AU Touillaud, MS Pillow, PC Jakovljevic, J Bondy, ML Singletary, SE Li, DH Chang, SN AF Touillaud, MS Pillow, PC Jakovljevic, J Bondy, ML Singletary, SE Li, DH Chang, SN TI Effect of dietary intake of phytoestrogens on estrogen receptor status in premenopausal women with breast cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID POSTMENOPAUSAL WOMEN; RISK-FACTORS; SOY; CONSUMPTION; BORON; CAROTENOIDS; ISOFLAVONES; POPULATION; PREVENTION; RECORDS AB Although many dietary studies have focused on breast cancer risk, few have examined dietary influence on tumor characteristics such as estrogen receptor (ER) status. Because phytoestrogens may modulate hormone levels and ER expression, we analyzed ER status and phytoestrogen intake in a case-case study of 124 premenopausal breast cancer patients. We assessed intake with a food-frequency questionnaire and obtained ER status from medical records. Rather than focusing on risk, we evaluated whether low intakes were more strongly associated with ER-negative tumors than with ER-positive disease. In logistic regression adjusting for potential confounders, threefold greater risks of ER-negative tumors relative to ER-positive tumors were associated with low intake of the isoflavones genistein (odds atio, OR = 3.50; 95% confidence interval, CI = 1.43-8.58) and daidzein (OR = 3.10; 95% CI = 1.31-7.30). Low intake of the flavonoid kaempferol (OR = 0.36; 95% CI = 0.16-0.83), the trace element boron (OR = 0.33; 95% CI = 0.13-0.83), and the phytosterol beta-sitosterol (OR = 0.42; 95% CI = 0.18-0.98) were associated with decreased risk of ER-negative tumors relative to ER-positive disease. Other phytoestrogens were not significantly associated with ER status. Thus, in premenopausal patients, some phytoestrogens may affect breast carcinogenesis by influencing ER status. Such findings suggest new directions for mechanistic research on dietary factors in breast carcinogenesis that may have relevance for prevention and clinical treatment. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Inst Gustave Roussy, EPIC, F-94805 Villejuif, France. NCI, Div Canc Prevent, Dept Hlth & Human Serv, Off Prevent Oncol,NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. RP Chang, SN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ChangSH@mail.nih.gov FU NCI NIH HHS [CA70264] NR 55 TC 31 Z9 33 U1 0 U2 5 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2005 VL 51 IS 2 BP 162 EP 169 DI 10.1207/s15327914nc5102_6 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 926XR UT WOS:000229157500006 PM 15860438 ER PT S AU Tataranni, P AF Tataranni, P BE Simopoulos, AP TI Metabolic syndrome: Is there a pathophysiological common denominator? Lessons learned from the Pima Indians SO Nutrition and Fitness: Obesity, the Metabolic Syndrome, Cardiovascular Disease, and Cancer SE WORLD REVIEW OF NUTRITION AND DIETETICS LA English DT Proceedings Paper CT 5th International Conference on Nutrition and Fitness CY JUN 09-12, 2004 CL Athens, GREECE ID INSULIN-RESISTANCE SYNDROME; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; CORONARY-HEART-DISEASE; SYMPATHETIC-NERVOUS-SYSTEM; BODY-WEIGHT GAIN; BLOOD-PRESSURE; PANCREATIC-POLYPEPTIDE; ESSENTIAL-HYPERTENSION; GLUCOCORTICOID ACTION; CORTISOL METABOLISM C1 NIDDK, Clin Diabet & Nutr Sect, DHHS, NIH, Phoenix, AZ USA. RP Tataranni, P (reprint author), NIDDK, Clin Diabet & Nutr Sect, DHHS, NIH, Phoenix, AZ USA. NR 57 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-7944-6 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2005 VL 94 BP 75 EP 83 DI 10.1159/000088221 PG 9 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics; Sport Sciences; Peripheral Vascular Disease SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics; Sport Sciences; Cardiovascular System & Cardiology GA BDN14 UT WOS:000234406800011 PM 16145253 ER PT J AU Gillum, RF Sempos, CT AF Gillum, R. F. Sempos, Christopher T. TI Ethnic variation in validity of classification of overweight and obesity using self-reported weight and height in American women and men: the Third National Health and Nutrition Examination Survey SO NUTRITION JOURNAL LA English DT Article AB Background: Few data have been published on the validity of classification of overweight and obesity based on self-reported weight in representative samples of Hispanic as compared to other American populations despite the wide use of such data. Objective: To test the null hypothesis that ethnicity is unrelated to bias of mean body mass index (BMI) and to sensitivity of overweight or obesity (BMI >= 25 kg/m(2)) derived from self-reported (SR) versus measured weight and height using measured BMI as the gold standard. Design: Cross-sectional survey of a large national sample, the Third National Health and Nutrition Examination Survey (NHANES III) conducted in 1988-1994. Participants: American men and women aged 20 years and over (n = 15,025). Measurements: SR height, weight, cigarette smoking, health status, and socio-demographic variables from home interview and measured weight and height. Results: In women and Mexican American (MA) men SR BMI underestimated true prevalence rates of overweight or obesity. For other men, no consistent difference was seen. Sensitivity of SR was similar in non-Hispanic European Americans (EA) and non-Hispanic African Americans (AA) but much lower in MA. Prevalence of obesity (BMI >= 30 kg/m(2)) is consistently underestimated by self-report, the gap being greater for MA than for other women, but similar for MA and other men. The mean difference between self-reported and measured BMI was greater in MA (men -0.37, women -0.76 kg/m(2)) than in non-Hispanic EA (men -0.22, women -0.62 kg/m(2)). In a regression model with the difference between self-reported and measured BMI as the dependent variable, MA ethnicity was a significant (p < 0.01) predictor of the difference in men and in women. The effect of MA ethnicity could not be explained by socio-demographic variables, smoking or health status. Conclusion: Under-estimation of the prevalence of overweight or obesity based on height and weight self-reported at interview varied significantly among ethnic groups independent of other variables. C1 [Gillum, R. F.] Ctr Dis Control & Prevent, Hyattsville, MD 20782 USA. [Sempos, Christopher T.] NIH, Bethesda, MD 20817 USA. RP Gillum, RF (reprint author), Ctr Dis Control & Prevent, 3311 Toledo Rd,Room 6323, Hyattsville, MD 20782 USA. EM rfg2@cdc.gov; cs217e@NIH.GOV NR 42 TC 138 Z9 139 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2891 J9 NUTR J JI Nutr. J. PY 2005 VL 4 AR 27 DI 10.1186/1475-2891-4-27 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V21OE UT WOS:000208216100027 PM 16209706 ER PT J AU Wise, LA Palmer, JR Rowlings, K Kaufman, RH Herbst, AL Noller, KL Titus-Ernstoff, L Troisi, R Hatch, EE Robboy, SJ AF Wise, LA Palmer, JR Rowlings, K Kaufman, RH Herbst, AL Noller, KL Titus-Ernstoff, L Troisi, R Hatch, EE Robboy, SJ TI Risk of benign gynecologic tumors in relation to prenatal diethylstilbestrol exposure SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FOLLOW-UP; UNITED-STATES; IN-UTERO; WOMEN; PREGNANCY; DES; STILBESTROL; ETIOLOGY; THERAPY; MICE AB OBJECTIVE: To investigate the association between prenatal diethylstilbestrol (DES) exposure and risk of benign gynecologic tumors. METHODS: We conducted a collaborative follow-up study of women with and without documented intrauterine exposure to DES. We compared the incidence of self-reported ovarian cysts, paraovarian cysts, and uterine leiomyomata confirmed by medical record in DES-exposed and unexposed women. RESULTS: A total of 85 cases of uterine leiomyomata and 168 cases of ovarian or paraovarian cysts were confirmed histologically. After adjustment for age, no association was found between prenatal DES exposure and ovarian cysts or uterine leiomyomata. Prenatal DES exposure was positively associated with paraovarian cysts. CONCLUSION: The present results do not support the hypothesis that prenatal DES exposure increases risk of uterine leiomyomata or ovarian cysts. Prenatal DES exposure was associated with an increased risk of paraovarian cysts, but detection bias cannot be ruled out as an explanation of this finding. (Obstet Gynecol 2005;105:167-73. (C) 2005 by The American College of Obstetricians and Gynecologists.). C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Baylor Coll Med, DES Screening Clin, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Tufts New England Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC USA. RP Wise, LA (reprint author), Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. EM lwise@slone.bu.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 FU NCI NIH HHS [N01-CP-21168, N01-CP-01289, N01-CP-51017] NR 33 TC 30 Z9 32 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2005 VL 105 IS 1 BP 167 EP 173 DI 10.1097/01.AOG.0000147839.74848.7c PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882IG UT WOS:000225932000027 PM 15625159 ER PT J AU Smith, TJ Stewart, PA Herrick, RF AF Smith, Tom J. Stewart, Patricia A. Herrick, Robert F. BE Gardiner, K Harrington, JM TI Retrospective exposure assessment SO OCCUPATIONAL HYGIENE, 3RD EDITION LA English DT Article; Book Chapter ID FIBER PRODUCTION WORKERS; OCCUPATIONAL EXPOSURE; HISTORICAL COHORT; CHEMICAL-AGENTS; AGREEMENT; CANCER C1 [Smith, Tom J.; Herrick, Robert F.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Stewart, Patricia A.] NCI, Occupat Studies Sect, Rockville, MD USA. RP Smith, TJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. NR 30 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-75507-5 PY 2005 BP 145 EP 159 DI 10.1002/9780470755075.ch12 D2 10.1002/9780470755075 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BXZ48 UT WOS:000297696600013 ER PT J AU Wolmark, N AF Wolmark, N TI Provocative optimism in the treatment of early stage disease - Introduction SO ONCOLOGIST LA English DT Editorial Material DE colorectal cancer; molecularly targeted agents; genomics; oxatiplatin ID ADVANCED COLORECTAL-CANCER; OXALIPLATIN; COLON C1 Allegheny Ctr 4, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Wolmark, N (reprint author), Allegheny Ctr 4, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. EM nwolmark@wahs.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2005 VL 10 SU 2 BP 1 EP 3 DI 10.1634/theoncologist.10-90002-1 PG 3 WC Oncology SC Oncology GA 988EB UT WOS:000233573300001 PM 16272452 ER PT J AU Budhu, AS Zipser, B Forgues, M Ye, QH Sun, ZT Wang, XW AF Budhu, AS Zipser, B Forgues, M Ye, QH Sun, ZT Wang, XW TI The molecular signature of metastases of human hepatocellular carcinoma SO ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Gastroenterological Carcinogenesis CY AUG 19-20, 2004 CL Sapporo, JAPAN DE hepatocellular carcinoma; liver cancer; metastasis; microarray; molecular profiling; osteopontin; prognosis ID CANCER-CELLS; GROWTH; TUMORS AB The current metastasis paradigm suggests that the primary tumor starts off benign but over time slowly acquires changes that provide a few rare cells within the tumor the ability to metastasize. However, this concept has been challenged by several recent studies using the microarray-based approach. We have recently found that the molecular signature of primary hepatocellular carcinoma (HCC) is very similar to that of their corresponding metastases, while it differs significantly in primary HCCs with or without metastasis. Similar findings are also evident in primary cancers of the lung, breast, and prostate. Such a signature can be used to predict he prognosis of HCC patients. Moreover, there are significant differences in the gene expression profiles of liver parenchyma among HCC patients with or without intrahepatic metastases. These findings imply that many of the metastasis-promoting genes are embedded in the primary tumors and that the ability to metastasize may be an inherent quality of the tumor from the beginning. In addition, the condition of liver parenchyma may dictate the intrahepatic metastasis potential, which is consistent with the hypothesis that the degree of viral-hepatitis-mediated liver damage or possibly the genetic makeup of individuals may play an important role in metastasis. Copyright (C) 2005 S. Karger AG, Basel. C1 NCI, Liver Carcinogenesis Grp, LHC, CCR,NIH, Bethesda, MD 20892 USA. Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. CAMS, Inst Canc, Natl Lab Mol Oncol, Beijing, Peoples R China. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Grp, LHC, CCR,NIH, 37 Convent Dr,MSC 4255,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 NR 21 TC 35 Z9 41 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2005 VL 69 SU 1 BP 23 EP 27 DI 10.1159/000086628 PG 5 WC Oncology SC Oncology GA 973RE UT WOS:000232539500005 PM 16210873 ER PT J AU Bertelli, G Garrone, O Bertolotti, L Occelli, M Conforti, S Marzano, N Febbraro, A Carlini, P Liossi, C Del Mastro, L Leonard, RCF AF Bertelli, G Garrone, O Bertolotti, L Occelli, M Conforti, S Marzano, N Febbraro, A Carlini, P Liossi, C Del Mastro, L Leonard, RCF TI Maintenance hormone therapy with letrozole after first-line chemotherapy for advanced breast cancer SO ONCOLOGY LA English DT Article DE breast cancer, advanced; CA 15-3; letrozole; maintenance therapy ID QUALITY-OF-LIFE; RANDOMIZED-TRIAL; INDUCTION TREATMENT; ONCOLOGY; SURVIVAL; EFFICACY; ACETATE AB Objectives: Maintenance hormone therapy after first-line chemotherapy is routinely used by many clinicians in advanced breast cancer patients with potentially hormone-sensitive tumors, although there are insufficient evidences in the literature to support this practice. We investigated the effects of the third-generation aromatase inhibitor letrozole as a maintenance therapy in postmenopausal patients who had responded or had stable disease with first-line chemotherapy. Methods: Fifty-eight patients (median age 62 years, range 31-80) were recruited and received letrozole, 2.5 mg/day starting within 8 weeks since the last cycle of chemotherapy. Estrogen and/or progesterone receptor status was positive in 81% of the patients, unknown in 19%; 57% of the patients had visceral disease. First-line chemotherapy included anthracyclines and/or taxanes in 74% of cases. Results: The median time to progression (TTP) from starting letrozole was 18.5 months. A shorter TTP was found in patients with abnormal CA 15-3 levels at the start of maintenance letrozole (median TTP, 9.9 months: p = 0.01), or with levels increasing >25% from baseline during the first 6 months of letrozole therapy (median TTP, 8.2 months: p < 0.0001). Response status improved during letrozole in 15.5% of patients who had obtained less than a complete response to chemotherapy. Maintenance treatment was well tolerated and had no significant impact on quality of life scores. Conclusions: This study provides evidence in support of the common clinical practice of maintenance hormone therapy after chemotherapy in suitably selected patients with advanced breast cancer. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Coll Swansea, SW Wales Canc Inst, Swansea, W Glam, Wales. Osped S Croce & Carle, SC Oncol Med, Cuneo, Italy. Osped Civile, Unita Operat Oncol, Cosenza, Italy. Osped San Paolo, Bari, Italy. Osped Fatebenefratelli, Unita Operat Oncol, Benevento, Italy. Ist Regina Elena, I-00161 Rome, Italy. Univ Coll Swansea, Dept Psychol, Swansea, W Glam, Wales. Natl Canc Inst, Genoa, Italy. RP Bertelli, G (reprint author), Singleton Hosp, Dept Oncol, Swansea SA2 8QA, W Glam, Wales. EM gianfilippo.bertelli@swansea-tr.wales.nhs.uk OI Liossi, Christina/0000-0003-0627-6377; Del Mastro, Lucia/0000-0002-9546-5841 NR 15 TC 12 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2005 VL 68 IS 4-6 BP 364 EP 370 DI 10.1159/000086976 PG 7 WC Oncology SC Oncology GA 958SQ UT WOS:000231468900010 PM 16020964 ER PT J AU Anderson, BD Schoenfeld, M AF Anderson, BD Schoenfeld, M CA Natl Canc I Clinical Invest EMMES Corporation TI Current phase III clinical trials investigating pediatric cancers SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; HIGH-RISK NEUROBLASTOMA; GERM-CELL TUMORS; INTERGROUP RHABDOMYOSARCOMA; CHEMOTHERAPY; CHILDREN; TRANSPLANTATION; ADOLESCENTS; ETOPOSIDE C1 NCI, Clin Invest Branch, CTEP, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Anderson, BD (reprint author), NCI, Clin Invest Branch, CTEP, Bethesda, MD 20892 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2005 VL 19 IS 1 BP 69 EP + PG 5 WC Oncology SC Oncology GA 052EA UT WOS:000238213000015 PM 15743152 ER PT J AU Woolery-Antill, M Carroll, E Wallen, G Jarosinski, P Corey, B Wieland, H Dagher, R AF Woolery-Antill, M Carroll, E Wallen, G Jarosinski, P Corey, B Wieland, H Dagher, R TI Assessing constipation in the pediatric oncology population: A pilot study. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2005 VL 32 IS 1 BP 204 EP 204 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300211 ER PT J AU Roh, ML Tuazon, CU Mandler, R Kwon-Chung, KJ Geist, CE AF Roh, ML Tuazon, CU Mandler, R Kwon-Chung, KJ Geist, CE TI Sphenocavernous syndrome associated with Schizophyllum commune infection of the sphenoid sinus SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Ophthalmic-Plastic-and-Reconstructive-Surgery CY NOV 13-15, 2003 CL ANAHEIM, CA SP Amer Soc Ophthalm Plast & Reconstruct Surg AB A 47-year-old diabetic man with chronic renal failure presented with a 1-month history of complete ptosis of the left upper eyelid, left proptosis, and left-sided headache. During the course of the patient's care, other significant diagnoses were excluded, such as orbital inflammatory syndrome, carotid-cavernous syndrome, and cavernous sinus thrombosis. Neuroimaging revealed only minimal left sphenoid sinus disease. Sphenoid biopsy revealed the presence of septate hyphae on Gram staining and produced a fungal culture characteristic of Schizophyllum commune. Minimal sphenoid sinus infection in a patient with chronic medical issues and probable immunosuppression predisposed this patient to fungal rhino-orbital infection. Several weeks of intravenous liposomal amphotericin treatment on an outpatient basis yielded resolution of clinical symptoms. C1 George Washington Univ, Dept Ophthalmol, Washington, DC USA. George Washington Univ, Dept Internal Med, Div Infect Dis, Washington, DC USA. George Washington Univ, Dept Neurol, Washington, DC USA. NIAID, Mol Microbiol Sect, Lab Clin Invest, NIH, Bethesda, MD 20892 USA. RP Roh, ML (reprint author), 2625 Highland Ave,404, Birmingham, AL 35205 USA. EM mroh3@yahoo.com NR 7 TC 13 Z9 14 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN PY 2005 VL 21 IS 1 BP 71 EP 74 DI 10.1097/01.IOP.0000148407.34787.6E PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 894BF UT WOS:000226764100014 PM 15677958 ER PT J AU Jernigan, HM Blum, PS Chakrabarti, I Su, Y Zigler, JS AF Jernigan, HM Blum, PS Chakrabarti, I Su, Y Zigler, JS TI Effects of cataractogenesis on the CDP-choline pathway: Increased phospholipid synthesis in lenses from galactosemic rats and 13/N guinea pigs SO OPHTHALMIC RESEARCH LA English DT Article DE rat lens; sugar cataract; strain 13/N guinea pig; cataracts; galactosemia; phospholipid synthesis; phosphatidylcholine; phosphatidylethanolamine; phosphocholine; phosphoethanolamine ID CULTURED GLIOMA-CELLS; PHOSPHATIDYLCHOLINE BIOSYNTHESIS; SUGAR CATARACT; MONKEY LENSES; PHOSPHORYLCHOLINE; PHOSPHORYLETHANOLAMINE; CHOLESTEROL; METABOLISM; XYLOSE; CRYSTALLIN AB We investigated the effects of cataractogenesis on phospholipid (P-lipid) synthesis in sugar cataracts from galactosemic rats and in hereditary cataracts from 13/N guinea pigs. Cataractous lenses from rats fed a 50% galactose diet for 7 days were incubated 24 h with radiolabeled choline or ethanolamine and the P-lipids were extracted. The galactosemic cataracts synthesized twice as much phosphatidylcholine (PtdCho) as control rat lenses, and phosphatidylethanolamine synthesis also was increased. Similar analysis of cataractous lenses from 3-week-old 13/N guinea pigs showed a 3-fold increase in PtdCho synthesis compared with control lenses. In all cases, the P-lipid precursor pool was lower in cataracts than in control lenses. The increased P-lipid synthesis in these cataracts may represent a membrane repair response to cataractogenic stress. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Tennessee, Dept Mol Sci, Memphis, TN 38163 USA. Univ Tennessee, Dept Ophthalmol, Memphis, TN 38163 USA. NEI, Lens & Cataract Biol Sect, Bethesda, MD 20892 USA. RP Jernigan, HM (reprint author), Univ Tennessee, Dept Mol Sci, 930 Madison Ave,Room 768, Memphis, TN 38163 USA. EM hjernigan@utmem.edu FU NEI NIH HHS [EY07938] NR 46 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHAL RES JI Ophthalmic Res. PY 2005 VL 37 IS 1 BP 7 EP 12 DI 10.1159/000082764 PG 6 WC Ophthalmology SC Ophthalmology GA 920BX UT WOS:000228663800002 PM 15604593 ER PT J AU Besada, P Mamedova, L Thomas, CJ Costanzi, S Jacobson, KA AF Besada, P Mamedova, L Thomas, CJ Costanzi, S Jacobson, KA TI Design and synthesis of new bicyclic diketopiperazines as scaffolds for receptor probes of structurally diverse functionality SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; P2Y(1) RECEPTOR; CONFORMATIONAL-ANALYSIS; P-2Y-PURINOCEPTOR AGONISTS; NUCLEOTIDE RECEPTORS; AMINO-ACIDS; IDENTIFICATION; DERIVATIVES; ANTAGONISTS; ANALOGS AB Diketopiperazines (DKPs) are a common motif in various biologically active natural products, and hence they may be useful scaffolds for the rational design of receptor probes and therapeutic agents. We constructed a new bicyclic scaffold that combines a DKP bridged with a 10-membered ring. In this way we obtained a three-dimensional molecular skeleton, with several amendable sites that provide a starting point to design a new combinatorial library having diverse substituent groups. Structural variation is based upon the flexibility of alkylation of the nitrogen atoms of the DKP and on the side-chain olefin. We obtained a 10-membered secondary ring through a ring-closure metathesis reaction using the second generation Grubbs catalyst. Rings containing both O-ethers and S-ethers were compared. N-Alkyl or arylalkyl groups were introduced optionally at the two Nα-atoms. This is a general scheme that will allow us to test rings of varying sizes, linkages, and stereochemical parameters. The DKP derivatives were tested for activity in astrocytoma cells expressing receptors coupled to phospholipase C. Inhibitory effects were observed for signaling elicited by activation of human nucleotide P2Y receptors but not m3 muscarinic receptors. Compound 20 selectively inhibited calcium mobilization (IC50 value of 486 &PLUSMN; 16 nM) and phosphoinositide turnover elicited by a selective P2Y(1) receptor agonist, but this compound did not compete for binding of a radiolabeled nucleotide-competitive receptor antagonist. Therefore, the new class of DKP derivatives shows utility as pharmacological tools for P2Y receptors. C1 NIDDK, Mol Recognit Sec, Lab Bioorgan Chem, Dept Hlth & Human Serv NIH, Bethesda, MD 20892 USA. RP Besada, P (reprint author), NIDDK, Mol Recognit Sec, Lab Bioorgan Chem, Dept Hlth & Human Serv NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; Besada Pereira, Pedro/E-6051-2012; OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK031115-24, Z01 DK070005-04] NR 46 TC 25 Z9 25 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2005 VL 3 IS 10 BP 2016 EP 2025 DI 10.1039/b416349d PG 10 WC Chemistry, Organic SC Chemistry GA 925QI UT WOS:000229067300028 PM 15889186 ER PT B AU Bodenreider, O Aubry, M Burgun, A AF Bodenreider, O Aubry, M Burgun, A BE Altman, RB Dunker, AK Hunter, L Jung, TA Klein, TE TI Non-lexical approaches to identifying associative relations in the gene ontology SO PACIFIC SYMPOSIUM ON BIOCOMPUTING 2005 LA English DT Proceedings Paper CT 10th Annual Pacific Symposium on Biocomputing (PSB) CY JAN 04-08, 2005 CL HI AB The Gene Ontology (GO) is a controlled vocabulary widely used for the annotation of gene products. GO is organized in three hierarchies for molecular functions, cellular components, and biological processes but no relations are provided among terms across hierarchies. The objective of this study is to investigate three non-lexical approaches to identifying such associative relations in GO and compare them among themselves and to lexical approaches. The three approaches are: computing similarity in a vector space model, statistical analysis of co-occurrence of GO terms in annotation databases, and association rule mining. Five annotation databases (FlyBase, the Human subset of GOA, MGI, SGD, and WormBase) are used in this study. A total of 7,665 associations were identified by at least one of the three non-lexical approaches. Of these, 12% were identified by more than one approach. While there are almost 6,000 lexical relations among GO terms, only 203 associations were identified by both non-lexical and lexical approacbes. The associations identified in this study could serve as the starting point for adding associative relations across hierarchies to GO, but would require manual curation. The application to quality assurance of annotation databases is also discussed. C1 US Natl Lib Med, Bethesda, MD 20894 USA. RP Bodenreider, O (reprint author), US Natl Lib Med, 8600 Rockville Pike,MS 43, Bethesda, MD 20894 USA. FU Intramural NIH HHS [Z99 LM999999] NR 10 TC 23 Z9 24 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-046-7 PY 2005 BP 91 EP 102 PG 12 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BCN48 UT WOS:000230169100008 PM 15759617 ER PT B AU Rogozin, IB Malyarchuk, BA Pavlov, YI Milanesi, L AF Rogozin, IB Malyarchuk, BA Pavlov, YI Milanesi, L BE Altman, RB Dunker, AK Hunter, L Jung, TA Klein, TE TI From context-dependence of mutations to molecular mechanisms of mutagenesis SO PACIFIC SYMPOSIUM ON BIOCOMPUTING 2005 LA English DT Proceedings Paper CT 10th Annual Pacific Symposium on Biocomputing (PSB) CY JAN 04-08, 2005 CL HI ID HUMAN MITOCHONDRIAL-DNA; ESCHERICHIA-COLI; SOMATIC HYPERMUTAGENESIS; POLYMERASE-ETA; CONTROL REGION; VIF PROTEIN; HYPERMUTATION; SPECIFICITY; SEQUENCES; SPECTRA AB Mutation frequencies vary significantly along. nucleotide sequences such that mutations often concentrate at certain positions called hotspots. Mutation hotspots in DNA reflect intrinsic properties of the mutation process, such as sequence specificity, that manifests itself at the level of interaction between mutagens, DNA, and the action of the repair and replication machineries. The nucleotide sequence context of mutational hotspots is a fingerprint of interactions between DNA and repair/replication/modification enzymes, and the analysis of hotspot context provides evidence of such interactions. The hotspots might also reflect structural and functional features of the respective DNA sequences and provide information about natural selection. We discuss analysis of 8-oxoguanine-induced mutations in pro- and eukaryotic genes, polymorphic positions in the human mitochondrial DNA and mutations in the HIV-1 retrovirus. Comparative analysis of 8-oxoguanine-induced mutations and spontaneous mutation spectra suggested that a substantial fraction of spontaneous A center dot T -> C center dot T mutations is caused by 8-oxoGTP in nucleotide pools. In the case of human mitochondrial DNA, significant differences between molecular mechanisms of mutations in hypervariable segments and coding part of DNA were detected. Analysis of mutations in the HIV-1 retrovirus suggested a complex interplay between molecular mechanisms of mutagenesis and natural selection. C1 NIH, Natl Ctr Biotechnol Informat NLM, Bethesda, MD 20894 USA. RP Rogozin, IB (reprint author), NIH, Natl Ctr Biotechnol Informat NLM, Bethesda, MD 20894 USA. OI Milanesi, Luciano/0000-0002-1201-3939 NR 48 TC 9 Z9 9 U1 0 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-046-7 PY 2005 BP 409 EP 420 PG 12 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BCN48 UT WOS:000230169100034 PM 15759646 ER PT J AU Beste, LA England, LJ Schisterman, EF Qian, C Yu, KF Levine, RJ AF Beste, LA England, LJ Schisterman, EF Qian, C Yu, KF Levine, RJ TI Pregnancy outcomes in smokers who develop pre-eclampsia SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID GESTATIONAL HYPERTENSION; CIGARETTE-SMOKING; GROWTH; RISK; ASSOCIATION; POPULATION; CALCIUM; TRIAL; RATES AB Maternal smoking reduces the risk of pre-eclampsia, but has been reported to increase the risk of adverse outcomes related to the disease. We used data from the trial of Calcium for Pre-eclampsia Prevention (CPEP) to explore whether clinical manifestations of pre-eclampsia were altered by maternal smoking. CPEP was a randomised study of 4589 nulliparous women conducted in five US medical centres. Smoking history was obtained at study enrolment and women were monitored for the development of hypertension, proteinuria, and other medical complications. Among pre-eclamptic women (n = 274), the risk of severe disease was not elevated in smokers (adjusted odds ratio 0.87 [95% confidence interval (CI) 0.30, 2.51]). Compared with non-smokers, gestational age (days, +/-SE) at onset of pre-eclampsia was not reduced in smokers (264.8 +/- 1.5, and 268.2 +/- 5.5, respectively, P = 0.48). The smoking-attributable deficit in birthweight was not increased in pre-eclamptic women compared with normotensive women (97 g [95% CI -49, 244] and 185 g [95% CI 141, 229] respectively). In conclusion, among women who developed pre-eclampsia, smoking during pregnancy was not associated with disease severity. We found no evidence that pre-eclampsia and smoking act synergistically to restrict fetal growth. C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. RP England, LJ (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,Mail Stop K-23, Atlanta, GA 30341 USA. EM lengland@cdc.gov OI Schisterman, Enrique/0000-0003-3757-641X FU NICHD NIH HHS [N01-HD-1-3121, N01-HD-1-3122, N01-HD-1-3123, N01-HD-1-3124, N01-HD-1-3125, N01-HD-1-3126, N01-HD-2-3154, N01-HD-53246] NR 19 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2005 VL 19 IS 1 BP 12 EP 18 DI 10.1111/j.1365-3016.2004.00617.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 889VJ UT WOS:000226470500003 PM 15670103 ER PT J AU Chescheir, NC AF Chescheir, NC TI Twin-to-twin transfusion syndrome: a model for the fetal origins of adult health SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Meeting on Investigation of Fetal Origins of Adult Health in Twin Cohorts CY APR, 2003 CL NICHD, Bethesda, MD HO NICHD ID CARDIAC DYSFUNCTION; RECIPIENT TWIN; SHEEP AB Twin-to-twin transfusion syndrome (TTTS) is a complication of monochorionic, diamniotic twins that results from unbalanced blood flow from one to the other in utero. The increased rate of functional heart disease among the recipient twins in these pregnancies is a model for the theory of fetal origins of adult health. Potential mechanisms for heart disease include alterations in the hormonal environment within the fetal bodies, blood pressure-driven alterations in blood flow and blood vessel distensibility, abnormal differentiation of fetal myocardial cells and changes in coronary artery growth. Although there are no large studies showing adult consequences of this fetal physiological disturbance, paediatric problems certainly exist and predict an increased risk of adult disease. C1 NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Chescheir, NC (reprint author), NICHHD, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B05 MSC 7510, Bethesda, MD 20892 USA. EM Nancy_Chescheir@med.unc.edu NR 14 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2005 VL 19 SU 1 BP 32 EP 36 DI 10.1111/j.1365-3016.2005.00612.x PG 5 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 900LM UT WOS:000227216400007 PM 15670119 ER PT J AU Luke, B Hediger, M Min, SJ Brown, MB Misiunas, RB Gonzalez-Quintero, VH Nugent, C Witter, FR Newman, RB Hankins, GDV Grainger, DA Macones, GA AF Luke, B Hediger, M Min, SJ Brown, MB Misiunas, RB Gonzalez-Quintero, VH Nugent, C Witter, FR Newman, RB Hankins, GDV Grainger, DA Macones, GA TI Gender mix in twins and fetal growth, length of gestation and adult cancer risk SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Meeting on Investigation of Fetal Origins of Adult Health in Twin Cohorts CY APR, 2003 CL NICHD, Bethesda, MD HO NICHD ID HUMAN CHORIONIC-GONADOTROPIN; CORONARY-HEART-DISEASE; OPPOSITE-SEX TWINS; BIRTH-WEIGHT; BREAST-CANCER; PRETERM BIRTH; IN-UTERO; INTRAUTERINE GROWTH; MATERNAL FACTORS; POPULATION AB This study evaluated the effect of gender mix (the gender combinations of twin pairs) on fetal growth and length of gestation, and reviewed the literature on the long-term effects of this altered fetal milieu on cancer risk. In singletons, it is well established that females weigh less than males at all gestations, averaging 125-135 g less at full term. This gender difference is generally believed to be the result of the effect of androgens on fetal growth. The gender difference in fetal growth is greater before the third trimester and less towards term, with males growing not only more, but also earlier than females. Plurality is a known risk factor for reduced fetal growth and birthweight. Compared with singletons, the mean birthweight percentiles of twins fall substantially (by 10% or more) below the singleton 10th percentile by 28 weeks, below the singleton 50th percentile by 30 weeks, and below the singleton 90th percentile by 34 weeks. In unlike-gender twin pairs, it has been reported that the female prolongs gestation for her brother, resulting in a higher birthweight for the male twin than that of like-gender male twins. Other researchers have demonstrated that females in unlike-gender pairs had higher birthweights than females in like-gender pairs. Analyses from our consortium on 2491 twin pregnancies with known chorionicity showed longer gestations and faster rates of fetal growth in both males and females in unlike-gender pairs compared with like-gender male or female pairs, although these differences were not statistically significant. The post-natal effects for females growing in an androgenic-anabolic environment include increased sensation-seeking behaviour and aggression, lowered visual acuity, more masculine attitudes and masculinising effects of the auditory system and craniofacial growth. In contrast, there is no evidence to suggest that there might be a similar feminising effect on males from unlike-gender pairs. This hormonal exposure in utero may influence adult body size and susceptability to breast cancer. C1 Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth Human Serv, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Div Hlth Care Policy & Res, Denver, CO USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Obstet & Gynecol, Ann Arbor, MI USA. Univ Miami, Sch Med, Dept Obstet & Gynecol, Miami, FL 33101 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Univ Texas, Med Branch, Dept Obstet & Gynecol, Galveston, TX 77550 USA. Univ Kansas, Sch Med, Dept Obstet & Gynecol, Wichita, KS 67214 USA. Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. RP Luke, B (reprint author), Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, 1801 NW 9th Ave,Room 200H, Miami, FL 33136 USA. EM bluke@med.miami.edu NR 68 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2005 VL 19 SU 1 BP 41 EP 47 DI 10.1111/j.1365-3016.2005.00616.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 900LM UT WOS:000227216400009 PM 15670121 ER PT J AU Dworkin, RH Turk, DC Farrar, JT Haythornthwaite, JA Jensen, MP Katz, NP Kerns, RD Stucki, G Allen, RR Bellamy, N Carr, DB Chandler, J Cowan, P Dionne, R Galer, BS Hertz, S Jadad, AR Kramer, LD Manning, DC Martin, S McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robbins, W Robinson, JP Rothman, M Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Wernicke, J Witter, J AF Dworkin, RH Turk, DC Farrar, JT Haythornthwaite, JA Jensen, MP Katz, NP Kerns, RD Stucki, G Allen, RR Bellamy, N Carr, DB Chandler, J Cowan, P Dionne, R Galer, BS Hertz, S Jadad, AR Kramer, LD Manning, DC Martin, S McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robbins, W Robinson, JP Rothman, M Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Wernicke, J Witter, J TI Core outcome measures for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review ID QUALITY-OF-LIFE; LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CONSORT STATEMENT; HEALTH-STATUS; POSTHERPETIC NEURALGIA; NEUROPATHIC PAIN; INSTRUMENTS; SCORES C1 Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Harvard Univ, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Univ Munich, D-80539 Munich, Germany. AstraZeneca, Wilmington, DE USA. Univ Queensland, Brisbane, Qld, Australia. Tufts Univ, Boston, MA 02111 USA. Merck & Co Inc, Blue Bell, PA USA. Amer Chron Pain Assoc, Rocklin, CA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. US FDA, Rockville, MD 20857 USA. Univ Toronto, Hlth Network, Toronto, ON, Canada. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut, E Hanover, NJ USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. NINDS, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14627 USA. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. NeurogesX, San Carlos, CA USA. Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, San Diego, CA 92103 USA. US Dept Vet Affairs, Washington, DC USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 NR 85 TC 1117 Z9 1134 U1 15 U2 80 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2005 VL 113 IS 1-2 BP 9 EP 19 DI 10.1016/j.pain.2004.09.012 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 891PG UT WOS:000226592400005 PM 15621359 ER PT J AU Parada, CA Reichling, DB Levine, JD AF Parada, CA Reichling, DB Levine, JD TI Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKC epsilon second messenger pathways SO PAIN LA English DT Article DE chronic pain; analgesia; inflammation; adenylyl cyclase; repetitive strain ID PROTEIN-KINASE-C; NOCICEPTOR SENSITIZATION; IN-VIVO; TRANSLOCATION; ANTAGONIST; INHIBITION; PROTECTION; ISOZYME; NEURONS; CELLS AB Toward the goal of defining new pharmacological targets for the treatment of chronic pain conditions, in previous studies we established a model, termed 'hyperalgesic prirning, in which an acute inflammatory stimulus causes a long-lasting latent susceptibility to hyperalgesia induced by subsequent exposures to the inflammatory mediator, prostaglandin E-2 (PGE(2)). Those investigations suggested the hypothesis that priming induces a novel linkage between the PGE(2)-activated second messenger cascade and the epsilon isoform of protein kinase C (PKCepsilon). In the present study, comparison of dose-response relations for hyperalgesia produced by PGE2(,) forskolin, 8-Br-cAMP, or the protein kinase A (PKA) catalytic Subunit, in primed versus normal animals, demonstrated that priming-induced enhancement of the PGE(2)-activated second messenger cascade occurs downstream to adenylate cyclase and upstream to PKA. Therefore, PGE(2)-induced hyperalgesia in the primed animal is enhanced by the recruitment of a novel cAMP/PKCepsilon signaling pathway in addition to the usual cAMP/PKA pathway. These observations suggest that pharmacological disruption of the novel interaction between cAMP and PKCepsilon might provide a route toward the development of highly specific methods to reverse cellular processes that underlie chronic pain states. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Room C-555,Campus Box 0440, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu RI Parada, Carlos Amilcar/C-3974-2012 FU NIDCR NIH HHS [DE 08973] NR 27 TC 73 Z9 75 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2005 VL 113 IS 1-2 BP 185 EP 190 DI 10.1016/j.pain.2004.10.021 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 891PG UT WOS:000226592400025 PM 15621379 ER PT J AU Kojima, M Ito, T Oono, T Hisano, T Igarashi, H Arita, Y Kawabe, K Coy, DH Jensen, RT Nawata, H AF Kojima, M Ito, T Oono, T Hisano, T Igarashi, H Arita, Y Kawabe, K Coy, DH Jensen, RT Nawata, H TI VIP attenuation of the severity of experimental pancreatitis is due to VPAC(1) receptor-mediated inhibition of cytokine production SO PANCREAS LA English DT Article DE vasoactive intestinal peptide; VPAC receptor; acute pancreatitis; monocyte; cytokine ID VASOACTIVE-INTESTINAL-PEPTIDE; RAT PERITONEAL-MACROPHAGES; IFN-GAMMA SYNTHESIS; MESSENGER-RNA; GUINEA-PIG; IN-VITRO; T-CELLS; GENE-EXPRESSION; POLYPEPTIDE; ACTIVATION AB Objectives: VIP receptor has been clarified to exist on immune cells, indicating its possible involvement in immunity and inflammatory response. Therefore, we investigated the effects of VIP and selective agonists for 2 subtypes of VIP receptor (VPAC(1)-R and VPAC(2)-R agonist) on acute pancreatitis. Methods: Acute pancreatitis was induced in mice by 4 intraperitoneal injections of cerulein and an injection of LPS. VIP, VPAC(1)-R agonist, VPAC(2)-R agonist, or secretin (5 nmol/body) was administered 30 minutes before and after the administration of LPS. Serum amylase and cytokine levels were determined, and histologic changes were evaluated. In vitro, IL-6 and TNF-alpha production by monocytes from the spleen was determined under the stimulation of LPS with VIP, VPAC(1)-R agonist, or VPAC(2)-R agonist, and the expression of VPAC(1)-R and VPAC(2)-R mRNA in monocytes was examined. Results: VPAC(1)-R agonist significantly decreased serum amylase, IL-6, and TNF-alpha, whereas VPAC(2)-R agonist markedly increased serum amylase. Histologically, VIP and VPAC(1)-R agonist attenuated the severity of pancreatitis, although VPAC(2)-R agonist or secretin showed no significant effect. In vitro, VPAC(1)-R and VPAC(2)-R mRNA were obviously expressed in monocytes. Under the stimulation with LPS, VIP presented a biphasic pattern that once decreased IL-6 production from monocytes and then enhanced at high concentration. VPAC(1)-R agonist reduced IL-6 levels, whereas VPAC(2)-R agonist increased IL-6 dose-dependently. VPAC(1)-R agonist reduced TNF-alpha levels in a dose-dependent manner. Conclusion: VIP attenuated the experimental acute pancreatitis enzymatically and morphologically by inhibiting proinflammatory cytokine production from monocytes mainly through the VPAC(1)-R. C1 Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. Tulane Univ, Hlth Sci Ctr, Dept Med, Peptide Res Labs, New Orleans, LA 70118 USA. RP Ito, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM itopapa@intmed3.med.kyushu-u.ac.jp NR 47 TC 32 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JAN PY 2005 VL 30 IS 1 BP 62 EP 70 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 885LJ UT WOS:000226157800009 PM 15632701 ER PT J AU Van Der Kolk, M De Vlas, SJ Saul, A Van De Vegte-Bolmer, M Eling, WM Sauerwein, W AF Van Der Kolk, M De Vlas, SJ Saul, A Van De Vegte-Bolmer, M Eling, WM Sauerwein, W TI Evaluation of the standard membrane feeding assay (SMFA) for the determination of malaria transmission-reducing activity using empirical data SO PARASITOLOGY LA English DT Article DE malaria; transmission-blocking activity; membrane feeding; Plasmodium falciparum; Anopheles stephensi; transmission-blocking vaccine ID PLASMODIUM-FALCIPARUM GAMETOCYTES; COMPETITION ELISAS; BLOCKING IMMUNITY; VIVAX MALARIA; INFECTIVITY; MOSQUITOS; AREA; ANTIBODIES; SERA; POPULATIONS AB Host responses to the transmittable stages of the malaria parasite may reduce transmission effectively. Transmission-reducing-activity (TRA) of human serum can be determined as a percentage, using the Standard Membrane Feeding Assay (SMFA). This laboratory assay was evaluated using the results of 121 experiments with malaria-endemic sera among which many repeated measurements were obtained. The assay consists of the feeding of Anopheles stephensi mosquitoes with cultured Plasmodium falciparum gametocytes, mixed with human red blood cells, and control and experimental sera. The TRA of individual sera was determined by the comparison of oocyst densities between these sera. Bootstrap data on oocyst densities in individual mosquitoes in control feeds were used to construct confidence limits for TRA percentages of serum feeds. Low (< 20parts per thousand) and high TRA (> 90parts per thousand) values for individual sera were usually reproduced in a second experiment, whereas this was more difficult for values between 20% and 90%. The observed variability of TRA values is explained in part by the variability in oocyst density per mosquito. Oocyst densities in control feeds varied more between experiments than within experiments and showed a slight decline over the 3 years of experiments. Reproducibility of TRA of field sera was low (20parts per thousand) between experiments, but much higher (61%) within experiments. A minimum of 35 oocysts per mosquito in control feeds gave optimal reproducibility (44%)) between experiments. We recommend that (1) sera are compared within an experiment, or (2) assays are only analysed, where controls have at least 35 oocysts per mosquito. The SMFA is under the recommended conditions appropriate for the study of factors that may influence TRA, e.g. transmission blocking vaccines. C1 UMC Nijmegen, NL-6500 HB Nijmegen, Netherlands. Inst Rech Dev, F-75480 Paris 10, France. OCEAC, Lab Rech Paludisme, Yaounde, Cameroon. Erasmus Univ, Ctr Med, Dept Publ Hlth, NL-3000 DR Rotterdam, Netherlands. NIAID LPD, Malaria Vaccine Dev Unit, NIH, Rockville, MD USA. RP Van Der Kolk, M (reprint author), UMC Nijmegen, PB 9101, NL-6500 HB Nijmegen, Netherlands. EM m.vanderkolk@ncmls.kun.nl RI Sauerwein, Robert/C-8519-2013; Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 29 TC 39 Z9 39 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0031-1820 J9 PARASITOLOGY JI Parasitology PD JAN PY 2005 VL 130 BP 13 EP 22 DI 10.1017/S0031182004006067 PN 1 PG 10 WC Parasitology SC Parasitology GA 891XC UT WOS:000226613300002 PM 15700753 ER PT J AU Reis, RM Reis, JS Longatto, A Tomarev, S Silva, P Lopes, JM AF Reis, RM Reis, JS Longatto, A Tomarev, S Silva, P Lopes, JM TI Differential Prox-1 and CD 31 expression in mucousae, cutaneous and soft tissue vascular lesions and tumors SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE Prox-1; CD 31; Kaposi's sarcoma; hemangioma; lymphangioma ID LYMPHATIC ENDOTHELIAL-CELLS; KAPOSIS-SARCOMA; GROWTH-FACTORS; MARKER; BLOOD; LYMPHANGIOGENESIS; ANGIOSARCOMAS; SYSTEM; ANGIOGENESIS; RECEPTORS AB The study of lymphatic vessels and lymphatic tumors has been hampered with difficulty due to the overlapping morphological features between blood and lymphatic endothelial cells, as well as to the lack of specific lymphatic endothelial markers. Over the last few years, lymphatic vessels and lymphangiogenesis have received great attention owing to their putative implications in terms of metastatic dissemination and the promise of targets for lymphangiogenic therapy. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis and is deemed to be a useful marker for differentiating lymphatic endothelial cells from the other blood vessels endothelial cells. Here, we describe a double-immunostaining strategy for formalin-fixed, paraffin-embedded tissues that aims at evaluating the distribution of Prox-1 and CD 31- a cytoplasmic pan-endothelial marker - in a series of 28 mucousae, cutaneous and soft tissue vascular lesions and tumors, including hemangiomas, lymphangiomas, lymphangiectasia, and Kaposi's sarcomas. Our results showed that in non-lesional mucousae and skin, Prox-1 decorated exclusively the nuclei of endothelial cells in lymphatic vessels. Prox-1 stained almost all the benign lymphatic vascular lesions/tumors (91%) and was absent or only focally positive in 75% of blood vascular tumors. CD 31 stained endothelial cells of blood vessels of superficial and deep dermal plexuses, lymphatics, and all blood vascular lesions/tumors. Kaposi's sarcomas were all positive for both CD 31 and Prox-1 markers. In conclusion, although Prox-1 expression in vascular lesions/tumors was not entirely restricted to tumors with known lymphatic differentiation, CD 31/Prox-1 double-immunolabeling can be used as an adjunct marker to identify lymphatic vessels in routinely processed formalin-fixed, paraffin-embedded samples. (c) 2005 Elsevier GmbH. All rights reserved. C1 Univ Porto, IPATIMUP, P-9200 Oporto, Portugal. Univ Minho, Sch Hlth Sci, ICVS, Life & Hlth Sci Inst, P-4719 Braga, Portugal. Inst Canc Res, Breakthrough Toby Robins Breast Canc Res Ctr, London SW3 6JB, England. Adolfo Lutz Inst, Div Pathol, Sao Paulo, Brazil. NEI, Mol & Dev Biol Lab, Sect Mol Mech Glaucoma, Bethesda, MD 20892 USA. Univ Porto, Dept Pathol, Fac Med, P-4100 Oporto, Portugal. RP Lopes, JM (reprint author), Univ Porto, IPATIMUP, Rua Roberto Frias S-N, P-9200 Oporto, Portugal. EM jmlopes@ipatimup.pt RI Lopes, Jose Manuel/J-7428-2013; Longatto Filho, Adhemar/A-2889-2016; longatto-filho, adhemar/D-7039-2013 OI Reis, Rui/0000-0002-9639-7940; Lopes, Jose Manuel/0000-0001-8597-3474; longatto-filho, adhemar/0000-0002-5779-9752 NR 31 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2005 VL 201 IS 12 BP 771 EP 776 DI 10.1016/j.prp.2005.08.010 PG 6 WC Pathology SC Pathology GA 000RA UT WOS:000234478800002 PM 16308102 ER PT J AU Kumar, S Pittaluga, S Raffeld, M Guierrera, M Seibel, N Jaffe, ES AF Kumar, S Pittaluga, S Raffeld, M Guierrera, M Seibel, N Jaffe, ES TI Primary cutaneous CD30-positive anaplastic large cell lymphoma in childhood: Report of 4 cases and review of the literature SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Review DE CD30; anaplastic lymphoma; pediatric; primary; cutaneous ID LYMPHOPROLIFERATIVE DISORDERS; NEUTROPHIL-RICH; PAPULOSIS; CHILDREN; KI-1; CLUSTERIN; DISEASE; LINEAGE; CLASSIFICATION; EXPRESSION AB We present the clinicopathologic findings in 4 children with primary cutaneous anaplastic large cell lymphoma (C-ALCL). The patients ranged in age from 13 months to 8 years, with 3 females and I male. All presented with a rapidly enlarging mass involving the skin and subcutaneous tissue. Histologic evaluation showed sheets of large pleomorphic lymphoid cells that were diffusely and strongly CD30(+). Tumor cells were CD45(+) in 1 of 4 cases. Cells were of T-cell phenotype, with variable positivity for CD3 (3 of 4 cases) and CD5 (2 of 4 cases). All 4 cases were positive for CD4 and clusterin. Staining for anaplastic lymphoma kinase was negative in all cases. No evidence of systemic involvement was noted at initial presentation or over a follow-up of 5 to 78 months, although 3 patients had cutaneous recurrences. Primary C-ALCL has only rarely been described in the pediatric population. The high-grade histologic appearance of this lymphoma belies its generally favorable clinical course and prognosis. Recognition of this entity and its differentiation from other T-cell lymphomas that secondarily involve the skin is important to avoid unnecessarily aggressive therapy in these children. C1 Childrens Natl Med Ctr, Dept Anat Pathol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. NCI, Hematopathol Sect, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), Vet Affairs Med Ctr, Dept Pathol & Lab Med 113, 50 Irving St, Washington, DC 20422 USA. EM shimareet.kumar@med.va.gov NR 37 TC 26 Z9 30 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD JAN-FEB PY 2005 VL 8 IS 1 BP 52 EP 60 DI 10.1007/s10024-004-8087-6 PG 9 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 908SD UT WOS:000227809600006 PM 15719203 ER PT J AU Domachowske, JB Rosenberg, HF AF Domachowske, JB Rosenberg, HF TI Advances in the treatment and prevention of severe viral bronchiolitis SO PEDIATRIC ANNALS LA English DT Article ID SYNCYTIAL VIRUS BRONCHIOLITIS; RESPIRATORY-TRACT INFECTION; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; AEROSOLIZED RIBAVIRIN; HUMAN METAPNEUMOVIRUS; NEBULIZED BUDESONIDE; ORAL DEXAMETHASONE; CHILDREN C1 SUNY Syracuse, Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Syracuse, Upstate Med Univ, Dept Pediat, 5th Floor,750 E Adams St, Syracuse, NY 13210 USA. NR 33 TC 9 Z9 9 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD JAN PY 2005 VL 34 IS 1 BP 35 EP 41 PG 7 WC Pediatrics SC Pediatrics GA 889IH UT WOS:000226436200006 PM 15693214 ER PT J AU Jacobs, RF Maples, HD Aranda, JV Espinoza, GM Knirsch, C Chandra, R Fisher, JM Kearns, GL AF Jacobs, RF Maples, HD Aranda, JV Espinoza, GM Knirsch, C Chandra, R Fisher, JM Kearns, GL TI Pharmacokinetics of intravenously administered azithromycin in pediatric patients SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE azithromycin; phannacokinetics; children ID ACUTE OTITIS-MEDIA; COMMUNITY-ACQUIRED PNEUMONIA; ANTIMICROBIAL SUSCEPTIBILITY; DOSE AZITHROMYCIN; CHILDREN; SURVEILLANCE; SINGLE; AMOXICILLIN; RESISTANCE; RATIONALE AB Background: The objective of this study was to characterize the pharmacokinetics and tolerance of a single intravenous (IV) azithromycin dose in children. Methods: Subjects were stratified into 4 age groups: 0.5-2 years; >2->6 years; 6-<12 years; and 12-<16 years. Each subject received a single 10 mg/kg dose (500 mg maximum) infused in 1 hour. Serial venous blood samples were obtained for a 168-hour period, and laboratory safety evaluations were performed immediately preceding azithromycin administration and at the conclusion of the study. Serum azithromycin concentrations were quantified with a validated high performance liquid chromatography method with mass spectrometric detection. Pharmacokinetic indices were calculated for each subject by noncompartmental techniques. Results: Thirty-two subjects (6.7 +/- 5.0 years, 11 boys) participated. Mean serum concentration-time data were comparable for the 4 age groups. For all subjects with evaluable data, the mean area under the curve from 0 to 72 hours (AUC(0-72)) was 8.2 mug (.) h/mL (n = 26), the maximum concentration (C(max)) was 2.4 mug/mL and the elimination half-life (t(1/2)) was 65.2 hours (n = 25). The AUC(0-72) and C(max) were not associated with age. The dose was well-tolerated with no serious adverse events. Conclusion: The disposition of azithromycin after a single 10 mg/kg IV dose (maximum labeled adult dose of 500 mg) is comparable in pediatric patients between 0.5 and 16 years of age. These pharmacokinetic data can be used to guide dose selection for future therapeutic trials of IV azithromycin in pediatric patients. C1 Arkansas Childrens Hosp, Div Pediat Infect Dis, Little Rock, AR 72202 USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Pfizer Inc, New York, NY USA. Pfizer Inc, Groton Labs, Groton, CT 06340 USA. Childrens Mercy Hosp & Clin, Kansas City, MO USA. NICHHD, Pediat Pharmacol Res Unit Network, Bethesda, MD 20892 USA. RP Jacobs, RF (reprint author), Arkansas Childrens Hosp, Div Pediat Infect Dis, 800 Marshall St, Little Rock, AR 72202 USA. EM jacobsrichardf@uams.edu FU NICHD NIH HHS [1 U10 HD 31324-06] NR 23 TC 14 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2005 VL 24 IS 1 BP 34 EP 39 DI 10.1097/01.inf.0000148927.48680.fc PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 889UC UT WOS:000226467100006 PM 15665708 ER PT J AU Paul, ME Chantry, CJ Read, JS Frederick, MM Lu, M Pitt, J Turpin, DB Cooper, ER Handelsman, EL AF Paul, ME Chantry, CJ Read, JS Frederick, MM Lu, M Pitt, J Turpin, DB Cooper, ER Handelsman, EL TI Morbidity and mortality during the first two years of life among uninfected children born to human immunodeficiency virus type 1-infected women - The women and infants transmission study SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY APR 29-MAY 13, 2001 CL BALTIMORE, MD SP Pediat Acad Soc DE human immunodeficiency virus infection; children morbidity; human immunodeficiency virus-uninfected ID PHYSICAL GROWTH; INFECTED WOMEN; UNITED-STATES; IMMUNOCOMPETENT INFANTS; VERTICAL TRANSMISSION; HIV-1 TRANSMISSION; CESAREAN-SECTION; NATIONAL-CENTER; EXPOSURE; PREVENTION AB Objective: We evaluated morbidity and mortality during the first 2 years of life among children born to human immunodeficiency virus-(HIV) type 1-infected women enrolled in the Women and Infants Transmission Study (WITS) during an 11-year period (1990-2001). Design and Methods: As part of WITS, evaluations were performed at birth and at 1, 2, 4, 6, 9, 12, 18 and 24 months of age. Growth, hospitalization and the incidence of clinical disease were assessed regularly. Results: Data regarding 1118 children born to HIV-infected women (955 HIV-uninfected children and 163 HIV-infected children) were analyzed. Fewer changes in the caretaker of the child and fewer periods of the study (all P values for time trend analyses <0.01). The percentages of HIV-uninfected children with poor weight gain (44 of 767; 5.7%), short stature (32 of 703; 4.5%) and wasting (27 of 792; 3.4%) were higher than expected for the general population. Two or more changes in caretaker were associated with all Growth deficiencies except wasting, and fetal exposure to tobacco was associated with height abnormalities. Anemia was common and was associated with receipt of zidovudine prophylaxis. Morbidity and mortality decreased during the study period. For the uninfected children, a decrease in class A events (Kaplan-Meier rates: group 1, 22.3%; group 2, 6.8%; group 3, 4.2%; P < 0.001) and class C events and death (Kaplan-Meier event rates: group 1, 2.0%; group 2, 1.7%; group 3, 0.2%; P = 0.062) during the first 2 years of life account for the differences in the curves over time. Conclusions: During an 11-year period, morbidity and mortality during the first 24 months of life decreased substantially for children born to HIV-infected women. C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. NICHHD, Bethesda, MD 20892 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Illinois, Chicago, IL USA. Boston Univ, Med Ctr, Boston, MA USA. SUNY Hlth Sci Ctr, Brookline, MA USA. Columbia Univ, New York, NY USA. RP Paul, ME (reprint author), Texas Childrens Hosp, 6621 Fannin St,FC 330-01, Houston, TX 77030 USA. EM mepaul@texaschildrenshospital.org FU NCRR NIH HHS [RR001888, RR00645]; NIAID NIH HHS [1 U01 AI 50274-01, N01 AI 85339, U01 AI 34841, U01 AI 34858]; NICHD NIH HHS [HD-3-6117, U01 HD 41983]; NIDA NIH HHS [9U01 DA 15054, U01 DA 15053] NR 51 TC 28 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2005 VL 24 IS 1 BP 46 EP 56 DI 10.1097/01.inf.0000148879.83854.7e PG 11 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 889UC UT WOS:000226467100008 PM 15665710 ER PT J AU Lefkowitz, W Lim, SY Lin, YH Salem, N AF Lefkowitz, W Lim, SY Lin, YH Salem, N TI Where does the developing brain obtain its docosahexaenoic acid? Relative contributions of dietary alpha-linolenic acid, docosahexaenoic acid, and body stores in the developing rat SO PEDIATRIC RESEARCH LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; N-3 DEFICIENCY; WHOLE-BODY; HUMAN-MILK; IN-VIVO; FORMULA; INFANT; METABOLISM; LIPIDS; LIVER AB Docosahexaenoic acid (DHA), a 22-carbon, highly unsaturated, n-3 fatty acid, is important for optimal nervous system function. In this study, designed to quantify how preformed dietary DHA regulates metabolic pathways in vivo, 8-d-old rat pups were divided into four groups and fed artificial rat milk diets. One group was fed formula with deuterium-labeled LNA (d5-LNA) as the only source of n-3 fatty acids, and a second group was fed formula that contained d5-LNA and unlabeled DHA. Two additional groups were dam-reared to permit analysis of fatty acyl pool sizes at postnatal days 8 and 28. The dams were fed a diet that contained 3% unlabeled LNA. DHA in brain and liver was analyzed. Our study demonstrated that preformed DHA in the diet markedly decreased the amount of biosynthesized DHA that accumulated in the brain and the liver. Surprisingly, similar to40% of the DHA that was newly acquired during this period in the "LNA" group was unlabeled. Because there were no unlabeled n-3 fatty acids in this diet, this DHA must have been derived from body stores of n-3 fatty acids. Thus, body stores can be a significant source of brain DHA in animals that are fed LNA as the only source of n-3 fatty acids. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Korea Maritime Univ, Div Ocean & Sci, Pusan 606791, South Korea. RP 12420 Parklawn Dr,Room 1-14, Rockville, MD 20852 USA. EM nsalem@niaaa.nih.gov RI Wilkinson, Stuart/C-2802-2013 NR 42 TC 41 Z9 41 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2005 VL 57 IS 1 BP 157 EP 165 DI 10.1203/01.PDR.0000147572.57627.AE PG 9 WC Pediatrics SC Pediatrics GA 882PW UT WOS:000225951800024 PM 15531740 ER PT J AU Dharnidharka, VR Agodoa, LY Abbott, KC AF Dharnidharka, VR Agodoa, LY Abbott, KC TI Children and older adults are at greatest risk for post transplant infections, but have a different infection profile. SO PEDIATRIC TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. NIDDK, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2005 VL 9 SU 6 MA 170 BP 85 EP 86 PG 2 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 957SB UT WOS:000231392500171 ER PT J AU Dharnidharka, VR Agodoa, LY Abbott, KC AF Dharnidharka, VR Agodoa, LY Abbott, KC TI Hospitalized urinary tract infection (UTI) at early, but not late, time points post kidney transplant in children is associated with earlier graft loss. SO PEDIATRIC TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. NIDDK, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2005 VL 9 SU 6 MA 307 BP 117 EP 117 PG 1 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 957SB UT WOS:000231392500307 ER PT J AU Dharnidharka, VR Agodoa, LY Abbott, KC AF Dharnidharka, VR Agodoa, LY Abbott, KC TI Differentiating the risk factors for bacterial infection or viral infection post kidney transplant. SO PEDIATRIC TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. NIDDK, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2005 VL 9 SU 6 MA 313 BP 118 EP 118 PG 1 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 957SB UT WOS:000231392500313 ER PT J AU Dharnidharka, VR Agodoa, LY Abbott, KC AF Dharnidharka, VR Agodoa, LY Abbott, KC TI Renal transplant recipients of pediatric age, or with primary diagnosis of lupus nephritis or reflux nephropathy, are at greater risk of post transplant infection. SO PEDIATRIC TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL USA. NIDDK, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2005 VL 9 SU 6 MA 316 BP 119 EP 119 PG 1 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 957SB UT WOS:000231392500316 ER PT B AU Bryant, SD Jinsmaa, Y Lazarus, LH AF Bryant, Sharon D. Jinsmaa, Yunden Lazarus, Lawrence H. BE Flegel, M Fridkin, M Gilon, C Slaninova, J TI Identification of opioid receptor ligand interactions using structurally related delta-opioid receptor agonists and antagonists and molecular modeling. SO Peptides 2004, Proceedings: BRIDGES BETWEEN DISCIPLINES LA English DT Proceedings Paper CT 3rd International Peptide Symposium/28th European Peptide Symposium CY SEP 05-10, 2004 CL Prague, CZECH REPUBLIC ID MUTATIONS; POTENT; MU C1 NIEHS, Med Chem Grp, Lab Chem & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Bryant, SD (reprint author), NIEHS, Med Chem Grp, Lab Chem & Pharmacol, Res Triangle Pk, NC 27709 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU KENES INT PI GENEVA 1 PA 17 RUE DU CENDRIER, PO BOX 1726, GENEVA 1, CH-1211, SWITZERLAND BN 965-90833-0-0 PY 2005 BP 702 EP 703 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEZ12 UT WOS:000240223200328 ER PT J AU Costa, P Samuels, J Bagby, M Daffin, L Norton, H AF Costa, Paul Samuels, Jack Bagby, Michael Daffin, Lee Norton, Hillary BE Maj, M Akiskal, HS Mezzich, JE Okasha, A TI Obsessive-Compulsive Personality Disorder: A Review SO PERSONALITY DISORDERS SE WPA Series in Evidence and Experience in Psychiatry LA English DT Review; Book Chapter ID DSM-III-R; BINGE-EATING DISORDER; NEO-PI-R; 5-FACTOR MODEL; AXIS-II; ANOREXIA-NERVOSA; DIAGNOSTIC AGREEMENT; INTERNAL CONSISTENCY; STRUCTURED INTERVIEW; 1ST-DEGREE RELATIVES C1 [Costa, Paul; Samuels, Jack; Bagby, Michael; Daffin, Lee; Norton, Hillary] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Costa, P (reprint author), NIA, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Samuels, Jack/0000-0002-6715-7905 NR 109 TC 14 Z9 15 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-09038-1 J9 WPA SER EVID EXPER P PY 2005 VL 8 BP 405 EP 439 DI 10.1002/0470090383.ch6 D2 10.1002/0470090383 PG 35 WC Psychiatry SC Psychiatry GA BYE02 UT WOS:000298178100071 ER PT J AU Duarte, SRR Carlson, O Egan, J Ralston, S AF Duarte, SRR Carlson, O Egan, J Ralston, S TI Effects of diet on Glucagon-Like Peptide-1 (GLP-1), Glucose and Insulin response of young horses SO PFERDEHEILKUNDE LA English DT Article; Proceedings Paper CT Equine Nutrition Conference for Feed Manufacturer CY 2005 CL Hannover, GERMANY ID HORMONE C1 Rutgers State Univ, Cook Coll, Dept Anim Sci, New Brunswick, NJ 08903 USA. NIH, Diabet Sect, Baltimore, MD USA. RP Ralston, S (reprint author), Rutgers State Univ, Cook Coll, Dept Anim Sci, New Brunswick, NJ 08903 USA. EM Ralston@aesop.rutgers.edu NR 16 TC 0 Z9 0 U1 0 U2 1 PU HIPPIATRIKA VERLAG MBH PI STUTTGART PA POSTFACH 102251, 70018 STUTTGART, GERMANY SN 0177-7726 J9 PFERDEHEILKUNDE JI Pferdeheilkunde PY 2005 VL 21 SU S BP 117 EP 119 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 995SE UT WOS:000234123300052 ER PT J AU Miller, MA Shahab, CK AF Miller, MA Shahab, CK TI Review of the cost effectiveness of immunisation strategies for the control of epidemic meningococcal meningitis SO PHARMACOECONOMICS LA English DT Article ID CAPSULAR POLYSACCHARIDE VACCINE; SUB-SAHARAN AFRICA; GROUP-A; ROUTINE IMMUNIZATION; BACTERIAL-MENINGITIS; CONJUGATE VACCINE; MASS VACCINATION; GROUP-B; DISEASE; CHILDREN AB Outbreaks of meningococcal disease have caused devastation worldwide. Effective vaccines have not been used routinely, due to perceived limitations of the duration of effectiveness as well as immunogenicity when administered during infancy. Given the sporadic nature of outbreaks, the optimal use of these vaccines to control both short-term epidemic and endemic meningococcal disease has been the subject of much debate. Seven economic studies on the use of polysaccharide vaccination strategies help to highlight the relevant epidemiological and economic issues surrounding the decisions for their use. Five of these studies were based in Africa, the region where annual incidence rates can be several orders of magnitude greater than the rest of the world. These studies demonstrated that vaccination against meningococcal disease during outbreak situations is suboptimal given the inability to rapidly immunise populations in a timely fashion in resource-poor areas. However, depending on the disease incidence and the ability to deliver vaccines, the polysaccharide vaccine can be cost effective for preventive strategies when given prior to the start of outbreaks, either through presumptive vaccination or through a modified routine delivery strategy. Economic analyses of mass immunisation campaigns and modelled routine vaccination suggest that routine use of meningococcal vaccines for preventive strategies could be within the range of cost-effective public health interventions in those regions of the world where meningococcal disease is endemic. This includes the meningococcal belt of Africa, the Sahelian region. C1 NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Miller, MA (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, 16 Ctr Dr MSC 6705,Bldg 16, Bethesda, MD 20892 USA. EM millermark@nih.gov NR 58 TC 11 Z9 11 U1 3 U2 6 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2005 VL 23 IS 4 BP 333 EP 343 DI 10.2165/00019053-200523040-00004 PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 926NU UT WOS:000229130700004 PM 15853434 ER PT J AU Zaykin, DV Young, SS AF Zaykin, DV Young, SS TI Large recursive partitioning analysis of complex disease pharmacogenetic studies. II. Statistical considerations SO PHARMACOGENOMICS LA English DT Article DE association mapping; data mining; false-discovery rates; linkage disequilibrium ID UNRELATED INDIVIDUALS; GENOTYPE DATA; ASSOCIATION; TRAITS; HAPLOTYPES; SUBGROUPS; LINKAGE; MODELS; DETECT; GENES AB Identifying genetic variations predictive of important phenotypes, such as disease susceptibility, drug efficacy, and adverse events, remains a challenging task. There are individual polymorphisms that can be tested one at a time, but there is the more difficult problem of the identification of combinations of polymorphisms or even more complex interactions of genes with environmental factors. Diseases, drug responses or side effects can result from different mechanisms. Identification of subgroups of people where there is a common mechanism is a problem for diagnosis and prescribing of treatment. Recursive partitioning (RP) is a simple statistical tool for segmenting a population into non-overlapping groups where the response of interest, disease susceptibility, drug efficacy and adverse events are more homogeneous within the segments. We suggest that the use of RP is not only more technically feasible than other search methods but it is less susceptible to multiple-testing problems. The numbers of combinations of gene-gene and gene-environment interactions is potentially astronomical and RP greatly reduces the effective search and inference space. Moreover, the certain reliance of RP on the presence of marginal effects is justifiable as was found by using analytical and numerical arguments. In the context of haplotype analysis, results suggest that the analysis of individual SNPs is likely to be successful even when susceptibilities are determined by haplotypes. Retrospective clinical studies where cases and controls are collected will be a common design. This report provides methods that can be used to adjust the RP analysis to reflect the population incidence of the response of interest. Confidence limits on the incidence of the response in the segmented subgroups are also discussed. RIP is a straightforward way to create realistic subgroups, and prediction intervals for the within-subgroup disease incidence are easily obtained. C1 Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. GlaxoSmithKline Inc, Genet Data Sci, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Young, SS (reprint author), Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. EM young@niss.org FU Intramural NIH HHS [Z01 ES101866-03] NR 28 TC 14 Z9 14 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2005 VL 6 IS 1 BP 77 EP 89 DI 10.1517/14622416.6.1.77 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 911CU UT WOS:000227979900013 PM 15723608 ER PT J AU Hiroi, T Wei, H Hough, C Leeds, P Chuang, DM AF Hiroi, T Wei, H Hough, C Leeds, P Chuang, DM TI Protracted lithium treatment protects against the ER stress elicited by thapsigargin in rat PC12 cells: roles of intracellular calcium, GRP78 and Bcl-2 SO PHARMACOGENOMICS JOURNAL LA English DT Article DE lithium; thapsigargin; ER stress; cytoprotection; GRP78; PC12 cells ID ENDOPLASMIC-RETICULUM STRESS; CEREBELLAR GRANULE CELLS; GLYCOGEN-SYNTHASE KINASE-3-BETA; CHRONIC VALPROATE TREATMENT; CEREBRAL CORTICAL-NEURONS; GLUTAMATE EXCITOTOXICITY; CULTURED NEURONS; SIGNALING PATHWAY; OXIDATIVE STRESS; APOPTOTIC DEATH AB We investigated the cytoprotective effects of lithium, the mood-stabilizer, on thapsigargin-induced stress on the endoplasmic reticulum ( ER) in rat PC12 cells. Protracted lithium pretreatment of PC12 cells elicited cytoprotection against thapsigargin-induced cytotoxicity. Lithium protection was concurrent with inhibition of thapsigargin-induced intracellular calcium increase and with elevated expression of the molecular chaperone GRP78. Moreover, lithium pretreatment upregulated the antiapoptotic protein Bcl-2, and blocked Bcl-2 downregulation elicited by thapsigargin. Prior to the induction of GRP78, lithium treatment alone increased the expression of c-Fos whose induction by ER stress is necessary for GRP78 induction. Curcumin, an inhibitor of transcription factor AP-1, blocked lithium cytoprotection against thapsigargin cytotoxicity. Thus, the induction of GRP78 and Bcl-2, and activation of AP-1 likely contribute to lithium-induced protection against cytotoxicity resulting from ER stress. Additionally, thapsigargin-induced cytotoxicity was suppressed by pretreatment with another mood-stabilizer, valproate, indicating that cytoprotection against ER stress is a common action of mood-stabilizing drugs. C1 NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Rm 4C-206,10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov NR 69 TC 63 Z9 66 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2005 VL 5 IS 2 BP 102 EP 111 DI 10.1038/sj.tpj.6500296 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 906YF UT WOS:000227680300006 PM 15668729 ER PT J AU Huang, R Wallqvist, A Thanki, N Covell, DG AF Huang, R Wallqvist, A Thanki, N Covell, DG TI Linking pathway gene expressions to the growth inhibition response from the National Cancer Institute's anticancer screen and drug mechanism of action SO PHARMACOGENOMICS JOURNAL LA English DT Article DE data mining; drug discovery; pathway; gene expression; cytotoxicity; small-molecule inhibitors ID MITOCHONDRIAL COMPLEX-I; CELL-LINES; IDENTIFICATION; DATABASE; CHEMOSENSITIVITY; RESISTANCE; PATTERNS; PROFILE AB Novel strategies are proposed to quantitatively analyze and relate biological pathways to drug responses using gene expression and small-molecule growth inhibition data (GI(50)) derived from the National Cancer Institute's 60 cancer cells (NCI60). We have annotated groups of drug GI(50) responses with pathways defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta, and functional categories defined by Gene Ontology ( GO), through correlations between pathway gene expression patterns and drug GI(50) profiles. Drug - gene- pathway relationships may then be utilized to find drug targets or target-specific drugs. Significantly correlated pathways and the gene products involved represent interesting targets for further exploration, whereas drugs that are significantly correlated with only certain pathways are more likely to be target specific. Separate pathway clustering finds that pathways engaged in the same biological process tend to have similar drug correlation patterns. The biological and statistical significances of our method are established by comparison to known small-molecule inhibitor - gene target relationships reported in the literature and by standard randomization procedures. The results of our pathway, gene expression and drug-induced growth inhibition associations, can serve as a basis for proposing testable hypotheses about potential anticancer drugs, their targets, and mechanisms of action. C1 NCI, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, NIH, Frederick, MD 21701 USA. RP Covell, DG (reprint author), NCI, Dev Therapeut Program, Screening Technol Branch, Lab Computat Technol, Bldg 1052-235, Frederick, MD 21702 USA. EM covell@ncifcrf.gov FU PHS HHS [N01 C0 12400] NR 32 TC 20 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2005 VL 5 IS 6 BP 381 EP 399 DI 10.1038/sj.tpj.6500331 PG 19 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 993UJ UT WOS:000233980400007 PM 16103895 ER PT J AU Holbl, A Kovacic, B Kerenyi, M Simma, O Cui, Y Beug, H Hennighausen, L Moriggl, R Sexl, V AF Holbl, A Kovacic, B Kerenyi, M Simma, O Cui, Y Beug, H Hennighausen, L Moriggl, R Sexl, V TI Clarifying the role of Stat5 in lymphoid development and abelson-induced transformation SO PHARMACOLOGY LA English DT Meeting Abstract CT Joint Meeting of the 11th Symposium of the Australian-Pharmacological-Society/Australian-Society-of-Toxicology/Hung arian-Society-for-Experiment-and-Clinical-Pharmacology CY NOV 24-26, 2005 CL Vienna, AUSTRIA SP Australian Pharmacol Soc, Australian Soc Toxicol, Hungarian Soc Exptl & Clin Pharmacol C1 Med Univ Vienna, Inst Pharmacol, Vienna, Austria. Inst Mol Pathol, A-1030 Vienna, Austria. Ludwig Boltzmann Inst Canc Res, Vienna, Austria. NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. RI Kovacic, Boris/J-1871-2016 OI Kovacic, Boris/0000-0002-1148-4149 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PY 2005 VL 75 IS 4 BP 197 EP 197 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 980TF UT WOS:000233040400012 ER PT J AU Thiagaraj, HV Russo, EB Burnett, A Goldstein, E Thompson, CM Parker, KK AF Thiagaraj, HV Russo, EB Burnett, A Goldstein, E Thompson, CM Parker, KK TI Binding properties of dipropyltryptamine at the human 5-HT1a receptor SO PHARMACOLOGY LA English DT Article DE serotonin; hallucinogens; cAMP; gamma-S-GTP ID DIFFERENTIAL INTERACTIONS; DRUG-INTERACTIONS; ADENYLYL-CYCLASE; SEROTONIN; PHARMACOLOGY; RHODOPSIN; PROTEINS; MIGRAINE; SUBTYPES; PEPTIDE AB Dipropyltryptamine (DPT) is a synthetic indolealkylamine first characterized in the 1960s. Largely forgotten since the discovery of multiple serotonin receptor subtypes, some of the properties of DPT at the cloned human 5-HT1a receptor are described here. When [H-3] 8-OH-DPAT is bound to the receptor, DPT inhibits the interaction with an IC50 of 0.1 mu mol/l. This interaction is shown to be competitive when double-reciprocal plots of the DPT/agonist interaction are analyzed. DPT's effects in the signal transduction system are complex. While DPT alone (0.1 - 1,000 mu mol/ l) activates G(i) when both cAMP and gamma-S-GTP incorporation are measured, in the presence of 5-HT ( 0.1 - 10 mu mol/l), DPT blocks the agonist effect. In combination, the findings suggest that DPT is a moderate affinity partial agonist at the human 5-HT1a receptor. These results provide evidence that DPT has potential as a versatile experimental tool at 5-HT1a receptors. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Montana, Sch Pharm & Allied Hlth Sci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. Univ Montana, Sch Pharm & Allied Hlth Sci, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. RP Univ Montana, Sch Pharm, Dept Pharmaceut Sci MPH 102, 32 Campus Dr 1552, Missoula, MT 59812 USA. EM keith.parker@umontana.edu FU NCRR NIH HHS [P20 RR15583]; NIGMS NIH HHS [GM54302-02]; NIH HHS [OD 54302-02] NR 44 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 EI 1423-0313 J9 PHARMACOLOGY JI Pharmacology PY 2005 VL 74 IS 4 BP 193 EP 199 DI 10.1159/000085649 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 947WZ UT WOS:000230679300005 PM 15886504 ER PT J AU Rosenberg, HF Bonville, CA Easton, AJ Domachowske, JB AF Rosenberg, HF Bonville, CA Easton, AJ Domachowske, JB TI The pneumonia virus of mice infection model for severe respiratory syncytial virus infection: identifying novel targets for therapeutic intervention SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE respiratory virus; pneumonia; chemokine; therapeutic; granulocyte ID MACROPHAGE-INFLAMMATORY PROTEIN-1-ALPHA; IL-8 GENE-EXPRESSION; PNEUMOVIRUS INFECTION; IN-VIVO; BRONCHIOLITIS; TRACT; DEGRANULATION; PATHOGENESIS; THERAPIES; MORTALITY AB Pneumonia virus of mice (PVM) is the first infection model that replicates features of severe human respiratory syncytial virus (hRSV) disease in the mouse. The PVM model has highlighted the importance of inflammation to the pathogenesis of severe disease, demonstrating that the inflammatory response remains active and acute even when virus replication ceases in response to appropriate antiviral therapy. The fact that the inflammatory response continues and is not completely linked to ongoing virus replication indicates the need for concurrent anti-inflammatory or, ideally, specific immunomodulatory therapy. The chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) and its receptor, CC chemokine receptor I (CCR1), have been identified as crucial to the inflammatory response to PVM and hRSV and thus as elements to exploit for potential immunomodulatory control. Biochemical blockade of MIP-1alpha signaling with the CCR1 antagonist met-RANTES prevents the inflammatory response to PVM and results in reduced morbidity and mortality when administered in conjunction with the antiviral agent ribavirin. Ongoing exploration into the biology of PVM infection will identify other pathways and targets to be exploited for immunomodulatory control of hRSV and related severe respiratory virus infections. (C) 2004 Elsevier Inc. All rights reserved. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Upstate Med Univ, Dept Pediat, Syracuse, NY USA. Univ Warwick, Coventry CV4 7AL, W Midlands, England. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov NR 38 TC 44 Z9 47 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2005 VL 105 IS 1 BP 1 EP 6 DI 10.1016/j.pharmthera.2004.09.001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 890XJ UT WOS:000226544200001 PM 15626452 ER PT J AU Pluta, RM AF Pluta, RM TI Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE cerebral vasospasm; nitric oxide; hemoglobin; ADMA ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; CANINE BASILAR ARTERY; PROTEIN-KINASE-C; SMOOTH-MUSCLE-CELLS; TRANSCRANIAL DOPPLER ULTRASOUND; INTRAARTERIAL PAPAVERINE INFUSION; ISCHEMIC NEUROLOGICAL DEFICITS; VASCULAR ENDOTHELIAL-CELLS; SOLUBLE GUANYLATE-CYCLASE; SUB-ARACHNOID HEMORRHAGE AB Despite years of research, delayed cerebral vasospasm remains the feared complication of a ruptured intracranial aneurysm. Worldwide effort has led to many promising experimental treatments that reverse or prevent cerebral vasospasm but none were confirmed to be effective in clinical trials. There are several sources for this failure: (1) the pathophysiology of delayed cerebral vasospasm remains poorly understood, (2) many experimental models of subarachnoid hemorrhage (SAH) do not mimic the actual clinical entity, and (3) many researchers erroneously extrapolate the data of peripheral and cerebral vascular physiological responses to the post-SAH situation. Thus, to explain the uniqueness of vasospasm and to address nitric oxide (NO) involvement in delayed vasospasm development, the following issues are addressed in this paper: (1) pathophysiological mechanisms of vasospasm, (2) NO-related contribution to its development. In addition, (3) a two-stage hypothesis of pathogenesis of delayed cerebral vasospasm is presented developed in the Vascular Laboratory of Surgical Neurology Branch of the National Institute of Neurological Disorders and Stroke using a primate model of SAH. According to this hypothesis, initially (Phase I) NO-releasing neurons are destroyed by oxyhemoglobin (oxyHb) leading to diminished availability of NO in the vessel wall and constriction of the vessels (Phase I). Increased shear stress evoked by narrowing of the arterial lumen should stimulate endothelial nitric oxide synthase (eNOS). But further metabolism of hemoglobin to bilirubin oxidized fragments (BOXes) increases asymmetric dimethylarginine (ADMA), an endogenous inhibitor of eNOS, in the vicinity of the artery further decreasing of NO availability and sustaining vasospasm (Phase II). In Phase III, the resolution of vasospasm, elimination of BOXes increases NO production by eNOS resulting in recovery of dilatory activity of endothelium. This hypothesis suggests that the key treatment to prevent delayed cerebral vasospasm should be focused on preventing oxyHb neurotoxicity, inhibiting BOX production, and exogenous NO delivery. (C) 2004 Elsevier Inc. All rights reserved. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM rysiek@ninds.nih.gov NR 555 TC 160 Z9 177 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2005 VL 105 IS 1 BP 23 EP 56 DI 10.1016/j.pharmthera.2004.10.002 PG 34 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 890XJ UT WOS:000226544200003 PM 15626454 ER PT J AU Leenders, AGM Sheng, ZH AF Leenders, AGM Sheng, ZH TI Modulation of neurotransmitter release by the second messenger-activated protein kinases: Implications for presynaptic plasticity SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE exocytosis; CaMKII (Ca2+/calmodulin-dependent kinase II); PKA (CAMP-dependent protein kinase A); PKC (protein kinase C); presynaptic proteins; synaptic plasticity ID LONG-TERM POTENTIATION; CYSTEINE-STRING PROTEIN; SYNAPTOSOME-ASSOCIATED PROTEIN; CULTURED HIPPOCAMPAL-NEURONS; SYNAPTIC-VESICLE FUSION; ADRENAL CHROMAFFIN CELLS; PARALLEL FIBER SYNAPSES; II MUTANT MICE; TRANSMITTER RELEASE; PHORBOL ESTERS AB Activity-dependent modulation of synaptic function and structure is emerging as one of the key mechanisms underlying synaptic plasticity. Whereas over the past decade considerable progress has been made in identifying postsynaptic mechanisms for synaptic plasticity, the presynaptic mechanisms involved have remained largely elusive. Recent evidence implicates that second messenger regulation of the protein interactions in synaptic vesicle release machinery is one mechanism by which cellular events modulate synaptic transmission. Thus, identifying protein kinases and their targets in nerve terminals, particularly those functionally regulated by synaptic activity or intracellular [Ca2+], is critical to the elucidation of the molecular mechanisms underlying modulation of neurotransmitter release and presynaptic plasticity. The phosphorylation and dephosphorylation states of synaptic proteins that mediate vesicle exocytosis could regulate the biochemical pathways leading from synaptic vesicle docking to fusion. However, functional evaluation of the activity-dependent phosphorylation events for modulating presynaptic functions still represents a considerable challenge. Here, we present a brief overview of the data on the newly identified candidate targets of the second messenger-activated protein kinases in the presynaptic release machinery and discuss the potential impact of these phosphorylation events in synaptic strength and presynaptic plasticity. (C) 2004 Elsevier Inc. All rights reserved. C1 NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. RP Sheng, ZH (reprint author), NINDS, Synapt Funct Unit, NIH, Bldg 35,Room 3B203,35 Convent Dr, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov FU NINDS NIH HHS [Z01 NS002946-09] NR 189 TC 77 Z9 83 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD JAN PY 2005 VL 105 IS 1 BP 69 EP 84 DI 10.1016/j.pharmthera.2004.10.012 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 890XJ UT WOS:000226544200005 PM 15626456 ER PT S AU Owens, IS Basu, NK Banerjee, R AF Owens, IS Basu, NK Banerjee, R BE Sies, H Packer, L TI UDP-Glucuronosyltransferases: Gene structures of UGT1 and UGT2 families SO PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS SE Methods in Enzymology LA English DT Review; Book Chapter ID URIDINE-DIPHOSPHATE-GLUCURONOSYLTRANSFERASE; POLYCYCLIC AROMATIC-COMPOUNDS; HUMAN BILIRUBIN; FUNCTIONAL-CHARACTERIZATION; HYDROXYLASE INDUCTION; SUBSTRATE-SPECIFICITY; GILBERTS-SYNDROME; COMPLEX LOCUS; AH RECEPTOR; 1ST EXONS AB In human, rat, and mice, a UGT1 complex locus provides for developmental-, inducer-, and cell-specific synthesis of a family of chemical-detoxifying isozymes, UDP-glucuronosyltransferases, which prevent toxicities, mutagenesis, and/or carcinogenesis. Between 10 and 14 first exons with individual promoter elements are tandemly arrayed upstream of 4 shared exons so as to synthesize independently as many overlapping primary transcripts. RNA splice sites allow a lead exon to join the common exons to generate mRNAs with unique 5' ends, but common 31 ends. Intra- and interspecies comparisons of amino acid sequences encoded by first exons show an evolutionary continuum; also, recognizable bilirubin- and phenol-specific catalytic units are differentially regulated by model compounds, phenobarbital, and/or aromatic hydrocarbons. Whereas UGT1 loci allow minimal changes to achieve new isozymes, a single deleterious mutation in a common exon negatively impacts the arrangement by inactivating the entire family of isozymes compared to an event at independent loci as seen in the UGT2 family. In humans, lethal hyperbilirubinemic Crigler-Najjar type 1 and milder diseases/syndromes are due to deleterious to mildly deleterious mutations in the bilirubin-specific UGT1A1 or a common exon. In addition, the number of TA repeats (N5-8) in the UGT1A1 proximal TATA box affects transcriptional rate and, thus, activity. Evidence also shows that polymorphisms in nonbilirubin-specific first exons also impact chemical detoxifications and other diseases. C1 NICHHD, Sect Genet Disorders Drug Metab, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Owens, IS (reprint author), NICHHD, Sect Genet Disorders Drug Metab, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 57 TC 60 Z9 60 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182805-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 400 BP 1 EP 22 DI 10.1016/S0076-6879(05)00001-7 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO60 UT WOS:000234565000001 PM 16399340 ER PT S AU Sugatani, J Sueyoshi, T Negishi, M Miwa, M AF Sugatani, J Sueyoshi, T Negishi, M Miwa, M BE Sies, H Packer, L TI Regulation of the human UGT1A1 gene by nuclear receptors constitutive active/androstane receptor, pregnane X receptor, and glucocorticoid receptor SO PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS SE Methods in Enzymology LA English DT Review; Book Chapter ID UDP-GLUCURONOSYLTRANSFERASE 1A1; CYTOCHROME-P450 GENES; ANDROSTANE RECEPTOR; RESPONSE ELEMENT; ENHANCER MODULE; METABOLISM; EXPRESSION; INDUCTION; CAR; FLAVONOIDS AB Human UDP-glueuronosyltransferase (UGT) 1A1 is the enzyme that detoxifies neurotoxic bilirubin by conjugating it with glucuronic acid. In addition to bilirubin, UGT1A1 conjugates various endogenous and exogenous lipophilic compounds such as estrogens and the active metabolite of the anticancer drug irinotecan SN-38. Thus, activation by specific inducers of the UGT1A1 gene is critical in treating patients with unconjugated hyperbilirubinemia and in preventing side effects of drug treatment such as SN-38-induced toxicity. This chapter describes the experimental processes used to identify the 290-bp distal enhancer module at -3499/-3210 of the UGT1A1 gene and to characterize its regulation by nuclear receptors: constitutive active/androstane receptor, pregnane X receptor, and glucocorticoid receptor. C1 Univ Shizuoka, Sch Pharmaceut Sci, Dept Pharmacobiochem & 21 COE, Shizuoka 422, Japan. Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. RP Sugatani, J (reprint author), Univ Shizuoka, Sch Pharmaceut Sci, Dept Pharmacobiochem & 21 COE, 395 Yada, Shizuoka 422, Japan. NR 26 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182805-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 400 BP 92 EP 104 DI 10.1016/S0076-6879(05)00006-6 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO60 UT WOS:000234565000006 PM 16399345 ER PT S AU Hempel, N Negishi, M McManus, ME AF Hempel, N Negishi, M McManus, ME BE Sies, H Packer, L TI Human SULT1A genes: Cloning and activity assays of the SULT1A promoters SO PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS SE Methods in Enzymology LA English DT Review; Book Chapter ID HUMAN ARYL SULFOTRANSFERASE; PHENOL SULFOTRANSFERASE; STRUCTURAL-CHARACTERIZATION; SUBSTRATE-SPECIFICITY; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; EXPRESSION; LOCALIZATION; CDNA; INHIBITION AB The three human SULT1A sulfotransferase enzymes are closely related in amino acid sequence (> 90%), yet differ in their substrate preference and tissue distribution. SULT1A1 has a broad tissue distribution and metabolizes a range of xenobiotics as well as endogenous substrates such as estrogens and iodothyronines. While the localization of SULT1A2 is poorly understood, it has been shown to metabolize a number of aromatic amines. SULT1A3 is the major catecholamine sulfonating form, which is consistent with it being expressed principally in the gastrointestinal tract. SULT1A proteins are encoded by three separate genes, located in close proximity to each other on chromosome 1.6. The presence of differential 5'-untranslated regions identified upon cloning of the SULT1A cDNAs suggested the utilization of differential transcriptional start sites and/or differential splicing. This chapter describes the methods utilized by our laboratory to clone and assay the activity of the promoters flanking these different untranslated regions found on SULT1A genes. These techniques will assist investigators in further elucidating the differential mechanisms that control regulation of the human SULT1A genes. They will also help reveal how different cellular environments and polymorphisms affect the activity of SULT1A gene promoters. C1 Univ Queensland, Sch Biomed Sci, Fac Biol & Chem Sci, Brisbane, Qld, Australia. Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. RP Hempel, N (reprint author), Univ Queensland, Sch Biomed Sci, Fac Biol & Chem Sci, Brisbane, Qld, Australia. RI Hempel, Nadine/F-1700-2014 OI Hempel, Nadine/0000-0002-5574-8783 NR 26 TC 9 Z9 11 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182805-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 400 BP 147 EP 165 DI 10.1016/S0076-6879(05)00009-1 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO60 UT WOS:000234565000009 PM 16399348 ER PT S AU Dean, M AF Dean, M BE Sies, H Packer, L TI Genetics of ATP-binding cassette transporters SO PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS SE Methods in Enzymology LA English DT Review; Book Chapter ID FAMILIAL INTRAHEPATIC CHOLESTASIS; DENSITY-LIPOPROTEIN DEFICIENCY; CAUSE PSEUDOXANTHOMA ELASTICUM; LINKED SIDEROBLASTIC ANEMIA; CORONARY-ARTERY DISEASE; DUBIN-JOHNSON-SYNDROME; CYSTIC-FIBROSIS GENE; ABC TRANSPORTER; MULTIDRUG-RESISTANCE; TANGIER-DISEASE AB The ATP-binding cassette (ABC) superfamily consists of membrane proteins that transport a wide variety of substrates across membranes. Mutations in ABC transporters cause or contribute to a number of different Mendelian disorders, including adrenoleukodystrophy, cystic fibrosis, retinal degeneration, cholesterol, and bile transport defects. In addition, the genes are involved in an increasing number of complex disorders. The proteins play essential roles in the protection of organisms from toxic metabolites and compounds in the diet and are involved in the transport of compounds across the intestine, blood-brain barrier, and the placenta. There are 48 ABC genes in the human genome divided into seven subfamilies based in gene structure, amino acid alignment, and phylogenetic analysis. These seven subfamilies are found in all other sequenced eukaryotic genomes and are of ancient origin. Further characterization of all ABC genes from humans and model organisms will lead to additional insights into normal physiology and human disease. C1 NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21701 USA. RP Dean, M (reprint author), NCI, Human Genet Sect, Lab Genom Divers, Frederick, MD 21701 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS NR 103 TC 102 Z9 106 U1 3 U2 8 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182805-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 400 BP 409 EP 429 DI 10.1016/S0076-6879(05)00024-8 PG 21 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO60 UT WOS:000234565000024 PM 16399363 ER PT J AU Inbaraj, JJ Kukielczak, BM Chignell, CF AF Inbaraj, JJ Kukielczak, BM Chignell, CF TI Phloxine B phototoxicity: A mechanistic study using HaCaT keratinocytes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID LIGHT-ACTIVATED TOXICITY; SINGLET OXYGEN; FREE-RADICALS; FRUIT-FLY; PHOTOSENSITIZED OXIDATION; LIPID-PEROXIDATION; BIOLOGICAL-SYSTEMS; XANTHENE DYES; DNA-DAMAGE; TEPHRITIDAE AB Phloxine B (PhB) (2',4',5',7'-tetrabromo-4,5,6,7-tetrachlorofluorescein; D&C Red No. 28) is a red dye found in drugs, cosmetics and foods; it is also currently being evaluated as a phototoxin for the potential control of fruit flies. Previous studies have shown that PhB is an efficient photosensitizer of damage to cellular membranes; thus, exposure of the skin to the dye and sunlight or artificial light may result in phototoxicity. Therefore, we have studied the phototoxicity of PhB and its structural analogue 2',7'-dichlorofluorescein (DCF) to HaCaT keratinocytes. Anaerobic visible irradiation (>400 nm) of PhB generated a semiquinone type radical, as detected by direct electron paramagnetic resonance. Aerobic visible irradiation of a reaction mixture containing PhB, the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and nicotinamide adenine dinucleotide (reduced) generated a superoxide dismutase-sensitive DMPO/O-2(.-) adduct. Irradiation of PhB and DCF in D2O generated singlet oxygen with quantum yields of 0.59 and 0.06, respectively. PhB was much more phototoxic than DCF when cell viability was measured using the 3-(4,5-dimethylthiazol-2yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. Visible irradiation of HaCaT keratinocytes in the presence of PhB (5 muM) resulted in a 90% decrease in cell viability. 3beta-Hydroxy-5alpha-cholest-6-ene-5-hydroperoxide, a singlet oxygen photoproduct of cholesterol, was isolated from HaCaT keratinocytes irradiated in the presence of PhB. Furthermore, PhB phototoxicity was inhibited by histidine and cysteine, quenchers of singlet oxygen. PhB (0.5 muM) and light irradiation also resulted in DNA damage, as measured by the Comet assay. The phototoxicity mechanism of PhB most probably initially involves a Type-II reaction with free radicals playing a minor role. However, secondary oxidative species such as radicals generated as a result of lipid peroxidation may serve to further promote oxidative damage. Our findings suggest that concern is warranted about the use of this dye in cosmetic products, as a food additive and in insecticidal sprays. C1 NIEHS, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, NIH, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov NR 32 TC 12 Z9 12 U1 1 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2005 VL 81 IS 1 BP 81 EP 88 DI 10.1562/2003-11-04-RA-002.1 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 898WL UT WOS:000227106800012 PM 15473832 ER PT J AU Bae, DS Andersen, ME Clewell, HJ AF Bae, Dong-Soon Andersen, Melvin E. Clewell, Harvey J., III BE Reddy, MB Yang, RSH Clewell, HJ Andersen, ME TI HALOGENATED ALKENES SO PHYSIOLOGICALLY BASED PHARMACOKINETICS MODELING: SCIENCE AND APPLICATIONS LA English DT Article; Book Chapter ID ORGANIC-SOLVENT VAPORS; POPULATION PHYSIOLOGICAL MODEL; BETA-CHLOROPRENE METABOLISM; MULTIROUTE EXPOSURE MODEL; CANCER RISK ASSESSMENT; TIME BREATH ANALYSIS; PHARMACOKINETIC MODEL; TRICHLOROACETIC-ACID; VINYL-CHLORIDE; IN-VITRO C1 [Bae, Dong-Soon] NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. [Andersen, Melvin E.] CIIT Ctr Hlth Res, Div Computat Biol, Res Triangle Pk, NC 27709 USA. [Clewell, Harvey J., III] CIIT Ctr Hlth Res, Ctr Human Hlth Assessment, Res Triangle Pk, NC 27709 USA. RP Bae, DS (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. OI Andersen, Melvin/0000-0002-3894-4811 NR 83 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-471-47876-8 PY 2005 BP 55 EP 78 DI 10.1002/0471478768.ch3 D2 10.1002/0471478768 PG 24 WC Toxicology SC Toxicology GA BXZ30 UT WOS:000297687000004 ER PT S AU Dabdoub, A Montcouquiol, M Kelley, MW AF Dabdoub, Alain Montcouquiol, Mireille Kelley, Matthew W. BE Mlodzik, M TI Planar cell polarity in the vertebrate inner ear SO PLANAR CELL POLARIZATION DURING DEVELOPMENT SE Advances in Developmental Biology LA English DT Article; Book Chapter ID DROSOPHILA TISSUE POLARITY; NEURAL-TUBE DEFECTS; 7-PASS TRANSMEMBRANE CADHERIN; EMBRYONIC-DEVELOPMENT; HAIR-CELLS; ASYMMETRIC LOCALIZATION; STEREOCILIARY BUNDLES; MAMMALIAN COCHLEA; SIGNALING PATHWAY; PDZ DOMAINS C1 [Dabdoub, Alain; Montcouquiol, Mireille; Kelley, Matthew W.] NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Kelley, MW (reprint author), NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. EM kelleymt@nidcd.nih.gov NR 76 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1574-3349 BN 978-0-08-045861-8 J9 AD DEV BIOL PY 2005 VL 14 BP 107 EP 130 DI 10.1016/S1574-3349(04)14006-4 PG 24 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BCR65 UT WOS:000311107700007 ER PT J AU Stewart, PE Byram, R Grimm, D Tilly, K Rosa, PA AF Stewart, PE Byram, R Grimm, D Tilly, K Rosa, PA TI The plasmids of Borrelia burgdorferi: essential genetic elements of a pathogen SO PLASMID LA English DT Review DE Lyme disease; spirochete; linear plasmid; incompatibility; telomere ID LYME-DISEASE SPIROCHETE; 32-KILOBASE CIRCULAR PLASMIDS; OUTER-SURFACE PROTEIN; OPEN READING FRAMES; INHIBITOR FACTOR-H; SENSU LATE STRAINS; LINEAR-PLASMID; ANTIGENIC VARIATION; EXTRACHROMOSOMAL DNAS; TELOMERE RESOLVASE AB The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, has an unusual genome comprised of a linear chromosome and the largest plasmid complement of any characterized bacterium. Certain plasmid-encoded elements are required for virulence and viability, both in vitro and in vivo. The genetic tools to; manipulate B. burgdorferi are sufficiently developed for precise molecular genetic investigations. B. burgdorferi now represents a prime system with which to address basic questions of plasmid biology and plasmid contributions to bacterial virulence and disease pathogenesis. Published by Elsevier Inc. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. RP Stewart, PE (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM pestewart@niaid.nih.gov NR 89 TC 52 Z9 53 U1 4 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0147-619X J9 PLASMID JI Plasmid PD JAN PY 2005 VL 53 IS 1 BP 1 EP 13 DI 10.1016/j.plasmid.2004.10.006 PG 13 WC Genetics & Heredity; Microbiology SC Genetics & Heredity; Microbiology GA 887OD UT WOS:000226314500001 PM 15631949 ER PT J AU Farma, J Nguyen, D AF Farma, J Nguyen, D TI Cardiac tamponade SO POSTGRADUATE MEDICAL JOURNAL LA English DT Editorial Material C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Farma, J (reprint author), NCI, Surg Branch, Bldg 10, Bethesda, MD 20892 USA. EM farmaj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0032-5473 J9 POSTGRAD MED J JI Postgrad. Med. J. PD JAN PY 2005 VL 81 IS 951 BP 67 EP 67 DI 10.1136/pgmj.2004.020768 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 885VR UT WOS:000226185800014 PM 15640435 ER PT B AU Baron, GS AF Baron, GS BE Kitamoto, T TI Prion protein interactions and TSE infections in cell culture models SO Prions: Food and Drug Safety LA English DT Proceedings Paper CT International Symposium of Prion Diseases for Food and Drug Safety CY OCT 31-NOV 02, 2004 CL Sendai, JAPAN SP Japan Intractable Dis Res Fdn DE exosomes; fluorescent PrP; microsome; prion; SN56 ID SCRAPIE AGENT; PC12 CELLS; IN-VITRO; RESISTANT; LINE; PRP; EXPRESSION; MEMBRANES; DISEASE; MULTIPLICATION AB The process by which transmissible spongiform encephalopathy (TSE) agents, or prions, infect cells is unknown. There are also no effective treatments available for TSE diseases. Studies of cultured cells persistently infected with TSE agents have greatly contributed to understanding these and many other aspects of TSE disease. New cell lines have been developed to increase the repertoire of TSE strains that can be investigated in ex vivo models. Candidates for TSE therapeutics have been identified. Initial events involving the internalization and trafficking of TSE agents and the effect of membranes on the infection process have been examined. Recent progress in these areas is discussed below, which together illustrate the value of cell culture models in the study of prion diseases. C1 NIAID, Lab Persistent Viral Dis, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Baron, GS (reprint author), NIAID, Lab Persistent Viral Dis, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-25539-7 PY 2005 BP 141 EP 153 DI 10.1007/4-431-29402-3_11 PG 13 WC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Infectious Diseases; Clinical Neurology; Neurosciences SC Biochemistry & Molecular Biology; Public, Environmental & Occupational Health; Infectious Diseases; Neurosciences & Neurology GA BCY14 UT WOS:000231843000011 ER PT B AU Gerber, LH Shah, J AF Gerber, LH Shah, J BE Battistella, LR Imamura, M TI Strategies for evaluation and treatment of a variety of patient problems: From the National Institutes of Health SO Proceedings of the 3rd World Congress of the International Society of Physical and Rehabilitation Medicine ISPRM LA English DT Proceedings Paper CT 3rd World Congress of the International-Society-of-Physical-and-Rehabilitation-Medicine (ISPRM) CY APR 10-15, 2005 CL Sao Paulo, BRAZIL DE osteogenesis imperfecta; myofascial pain; foot management; cancer C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gerber, LH (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-7587-137-X PY 2005 BP 69 EP 70 PG 2 WC Medicine, General & Internal; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BDG81 UT WOS:000233428700015 ER PT B AU Gerber, LH Joe, GO AF Gerber, LH Joe, GO BE Battistella, LR Imamura, M TI Current approaches to the evaluation and treatment of chronic regional pain syndrome SO Proceedings of the 3rd World Congress of the International Society of Physical and Rehabilitation Medicine ISPRM LA English DT Proceedings Paper CT 3rd World Congress of the International-Society-of-Physical-and-Rehabilitation-Medicine (ISPRM) CY APR 10-15, 2005 CL Sao Paulo, BRAZIL DE chronic pain; autonomic dysfunction; rehabilitation; CRPS C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gerber, LH (reprint author), NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-7587-137-X PY 2005 BP 941 EP 942 PG 2 WC Medicine, General & Internal; Rehabilitation SC General & Internal Medicine; Rehabilitation GA BDG81 UT WOS:000233428700175 ER PT B AU Le, SY Maizel, JV AF Le, SY Maizel, JV BE Blair, S Chakraborty, U Chen, SH Cheng, HD Chiu, DKY Das, S Denker, G Duro, R Romay, MG Hung, D Kerre, EE VaLeong, H Lu, CT Lu, J Maguire, L Ngo, CW Sarfraz, M Tseng, C Tsumoto, S Ventura, D Wang, PP Yao, X Zhang, CN Zhang, K TI Finding double-stranded RNA structures in the 3' untranslated region of eukaryotic mRNAs SO Proceedings of the 8th Joint Conference on Information Sciences, Vols 1-3 LA English DT Proceedings Paper CT 8th Joint Conference on Information Sciences (JCIS 2005) CY JUL 21-26, 2005 CL Salt Lake City, UT SP Duke Univ, Utah State Univ, San Jose State Univ, Harbin Inst Technol ID SECONDARY STRUCTURES; LOCALIZATION; RECOGNITION; SEQUENCES; PROTEIN AB Recent development in the study of RNA silencing indicates that double-stranded RNA (dsRNA) can be used in eukaryotes to block expression of a corresponding cellular gene. In the RNA interference (RNAi) pathway, dsRNAs serve as the initial trigger that are chopped by an ribonuclease termed "Dicer" and result in mRNA degradation and aberrant. It has reported that a large dsRNA structure in the 3' untranslated region (3'UTR) may correlate with the translation suppression. In this study, we search for dsRNA structures in the UTR database. The occurrence rate of the large dsRNA structure in 3'UTRs ranges from 0.01% in plant to 0.30% in vertebrate mRNAs. However, small dsRNAs of 21-23 bp are much more than the large one. These dsRNAs are very significant in Monte Carlo simulations and are uniquely well-ordered. The detected dsRNA structure in the 3'UTR of Drosophila bicoid is in good agreement with the cis-acting element that plays a key role in the translational repression and localization. Our data mining of dsRNAs can be used to explore possible RNAi in the RNA-based regulation of gene expression. C1 NCI, CCR, Lab Expt & Computat Biol, NIH, Ft Detrick, MD 21702 USA. RP Le, SY (reprint author), NCI, CCR, Lab Expt & Computat Biol, NIH, Bldg 469,Room 151, Ft Detrick, MD 21702 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU JOINT CONFERENCE INFORMATION SCIENCES PI DURHAM PA 2709 MONTGOMERY ST, DURHAM, NC 27705 USA PY 2005 BP 1273 EP 1277 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Computer Science GA BDI96 UT WOS:000233670802023 ER PT B AU Thoma, GR Mao, S Misra, D AF Thoma, GR Mao, S Misra, D BE Villanueva, JJ TI Automated metadata extraction to preserve the digital contents of biomedical collections SO Proceedings of the Fifth IASTED International Conference on Visualization, Imaging, and Image Processing LA English DT Proceedings Paper CT 5th IASTED International Conference on Visualization, Imaging, and Image Processing CY SEP 07-09, 2005 CL Benidorm, SPAIN SP Int Assoc Sci & Technol Dev DE digital preservation; SPER; and automated metadata extraction AB The long term preservation of digital objects, a growing problem as these are acquired by libraries and archives, requires appropriate systems, standards and institutional policies. A key requirement is the acquisition of metadata about the objects to enable future access and usage, as well as the migration of digital files from obsolete formats to newer ones. "Metadata", is data about data. It typically consists of information about the intellectual content of a digital object, the data required for appropriate digital representation and interpretation, security or rights management information, and their relation to other digital objects. The manual recording of these metadata elements is highly labor-intensive and automated means for doing this are key to successful preservation. In this paper a prototype system for digital preservation is introduced, its main functions are described highlighting the strategies adopted in designing the system to meet these functionalities in a modular and cost-effective manner, an automated metadata extraction subsystem to minimize manual entry, using string matching and machine learning techniques, is presented, and preliminary performance assessments are given. C1 US Natl Lib Med, Bethesda, MD 20894 USA. RP Thoma, GR (reprint author), US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU ACTA PRESS PI CALGARY PA B6, STE 101, 2509 DIEPPE AVE SW, CALGARY, ALBERTA T3E 7J9, CANADA BN 0-88986-528-0 PY 2005 BP 214 EP 219 PG 6 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BDH65 UT WOS:000233581700039 ER PT J AU Read, J AF Read, J TI Early computational processing in binocular vision and depth perception SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review ID INFERIOR TEMPORAL CORTEX; CATS VISUAL-CORTEX; STEREO CORRESPONDENCE PROBLEM; DISPARITY-SELECTIVE NEURONS; CLASSICAL RECEPTIVE-FIELD; RANDOM-DOT STEREOGRAMS; MACAQUE V1 NEURONS; STRIATE CORTEX; HORIZONTAL DISPARITY; SIMPLE CELLS AB Stereoscopic depth perception is a fascinating ability in its own right and also a useful model of perception. In recent years, considerable progress has been made in understanding the early cortical circuitry underlying this ability. Inputs from left and right eyes are first combined in primary visual cortex (V1), where many cells are tuned for binocular disparity. Although the observation of disparity tuning in V1, combined with psychophysical evidence that stereopsis must occur early in visual processing, led to initial suggestions that V1 was the neural correlate of stereoscopic depth perception, more recent work indicates that this must occur in higher visual areas. The firing of cells in V1 appears to depend relatively simply on the visual stimuli within local receptive fields in each retina, whereas the perception of depth reflects global properties of the stimulus. However, V1 neurons appear to be specialized in a number of respects to encode ecologically relevant binocular disparities. This suggests that they carry out essential preprocessing underlying stereoscopic depth perception in higher areas. Thus article reviews recent progress in developing accurate models of the computations carried out by these neurons. We seem close to achieving a mathematical description of the initial stages of the brain's stereo algorithm. This is important in itself-for instance, it may enable improved stereopsis in computer vision-and paves the way for a full understanding of how depth perception arises. Published by Elsevier Ltd. C1 NIH, Bethesda, MD 20892 USA. RP Read, J (reprint author), NIH, 49-2A50 Convent Dr, Bethesda, MD 20892 USA. RI Read, Jenny/A-7493-2013 OI Read, Jenny/0000-0002-9029-5185 FU NEI NIH HHS [Z01 EY000404-04] NR 128 TC 20 Z9 20 U1 2 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JAN PY 2005 VL 87 IS 1 BP 77 EP 108 DI 10.1016/j.pbiomolbio.2004.06.005 PG 32 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 864WW UT WOS:000224664700007 PM 15471592 ER PT S AU Miranda, KM Ridnour, L Esprey, M Citrin, D Thomas, D Mancardi, D Donzelli, S Wink, DA Katori, T Tocchetti, CG Ferlito, M Paolocci, N Fukuto, JM AF Miranda, Katrina M. Ridnour, Lisa Esprey, Michael Citrin, Deborah Thomas, Douglas Mancardi, Daniele Donzelli, Sonia Wink, David A. Katori, Tatsuo Tocchetti, Carlo G. Ferlito, Marcella Paolocci, Nazareno Fukuto, Jon M. BE Karlin, KD TI Comparison of the Chemical Biology of NO and HNO: An Inorganic Perspective SO PROGRESS IN INORGANIC CHEMISTRY, VOL 54 SE PROGRESS IN INORGANIC CHEMISTRY LA English DT Review; Book Chapter ID SOLUBLE GUANYLATE-CYCLASE; NITRIC-OXIDE SYNTHASE; RESONANCE RAMAN-SPECTROSCOPY; HYDROXY-L-ARGININE; CYTOTOXIC ACTIVATED MACROPHAGES; TRANSITION-METAL COMPLEXES; DETERRENT AGENT CYANAMIDE; NITROXYL DELIVERY AGENTS; AQUEOUS-SOLUTION; SUPEROXIDE-DISMUTASE C1 [Ridnour, Lisa; Esprey, Michael; Citrin, Deborah; Thomas, Douglas; Mancardi, Daniele; Donzelli, Sonia; Wink, David A.] NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Miranda, Katrina M.] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. [Katori, Tatsuo; Tocchetti, Carlo G.; Ferlito, Marcella; Paolocci, Nazareno] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Fukuto, Jon M.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. RP Wink, DA (reprint author), NCI, Tumor Biol Sect, Radiat Biol Branch, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009; OI tocchetti, carlo gabriele/0000-0001-5983-688X; MANCARDI, Daniele/0000-0003-3809-6047 NR 240 TC 8 Z9 8 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0079-6379 BN 978-0-471-72348-6 J9 PROG INORG CHEM JI Prog. Inorgan. Chem. PY 2005 VL 54 BP 349 EP 384 DI 10.1002/0471725560.ch5 PG 36 WC Chemistry, Inorganic & Nuclear SC Chemistry GA BJI32 UT WOS:000266102000005 ER PT J AU Vamecq, J Vallee, L Lesage, F Gressens, P Stables, JP AF Vamecq, J Vallee, L Lesage, F Gressens, P Stables, JP TI Antiepileptic popular ketogenic diet: emerging twists in an ancient story SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID K-ATP CHANNELS; PROLIFERATOR-ACTIVATED RECEPTOR; POLYUNSATURATED FATTY-ACIDS; SENSITIVE POTASSIUM CHANNELS; PORE-FORMING SUBUNIT; MITOCHONDRIAL UNCOUPLING PROTEINS; INTRACTABLE SEIZURE DISORDERS; MEDIUM-CHAIN TRIGLYCERIDES; FOCAL CEREBRAL-ISCHEMIA; RAT NEURONAL CULTURES AB The antiepileptic activity associated with ketogenic diets (KD) have been known for some time. First reports date back to the Middle Ages and even Biblical times where KD was achieved by fasting (i.e. "water diet") [see Swink, T.D., Vining, E.P.G., Freeman, J.M., 1997. The ketogenic diet: 1997. Adv. Pediatr. 44, 297-329, and references therein]. In the early 20th century, changes in the design of the KD were introduced, shifting the so-called "water diet" to a high-fat diet. Initial clinical evaluations undertaken between the 1920s and 1940s were enthusiastic, but the popularity of the KD was retrograded upon clinical introduction of phenytoin and subsequently other antiepileptic drugs. Today, despite a pharmacological arsenal targeting cerebral receptors and specific events in seizure initiation and development, about 30-40% patients are still refractory to available medications. Thus, the KD has been re-introduced in recent years as an alternative therapy, averring to be efficacious against some instances of resistant or intractable epilepsy. Despite a long historical background and enlarged clinical use, identification of the underlying anticonvulsant mechanisms associated with this nonpharmacological approach is still in stagnation. The present review is an attempt to encourage current research orientation through well-based and directed proposals for putative emerging candidates mediating KD anticonvulsant mechanisms. The reader is provided with a special emphasis on ATP-sensitive and recently cloned two-pore (or tandem) domain potassium channels, as well as several emerging conceptual views and advances such as nuclear receptors, uncoupling proteins and gap junctions that the authors speculate may contribute to understanding the basic mechanisms linked to the KD. (c) 2004 Elsevier Ltd. All rights reserved. C1 CHRU Lille, INSERM, UNIV 045131, Salengro Univ Hosp, F-59037 Lille, France. Univ Lille 2, EA1046, Fac Med, F-59045 Lille, France. CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097, F-06560 Valbonne, France. CHU Nice, Serv Neurol, Hop Pasteur, F-06002 Nice, France. Hop Robert Debre, INSERM, E9935, F-75019 Paris, France. NINDS, Preclin Pharmacol Sect, Epilepsy Branch, DCDND,NIH, Bethesda, MD 20892 USA. RP Vamecq, J (reprint author), CHRU Lille, INSERM, UNIV 045131, Salengro Univ Hosp, F-59037 Lille, France. EM vamecq@lille.inserm.fr RI Lesage, Florian/D-5097-2011; OI Lesage, Florian/0000-0002-4406-7106; Gressens, Pierre/0000-0002-0909-4221 NR 230 TC 29 Z9 31 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JAN PY 2005 VL 75 IS 1 BP 1 EP 28 DI 10.1016/j.pneurobio.2004.11.003 PG 28 WC Neurosciences SC Neurosciences & Neurology GA 905LR UT WOS:000227570200001 PM 15713528 ER PT S AU Liu, QR Gong, JP Uhl, GR AF Liu, QR Gong, JP Uhl, GR BE Moldave, K TI Families of protein phosphatase 1 modulators activated by protein kinases A and C: Focus on brain SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 79 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review; Book Chapter ID REGULATED NEURONAL PHOSPHOPROTEIN; LIGHT-CHAIN PHOSPHATASE; RABBIT SKELETAL-MUSCLE; DARPP-32 KNOCKOUT MICE; ARTERIAL SMOOTH-MUSCLE; INTEGRIN-LINKED KINASE; MYOSIN PHOSPHATASE; IMMUNOCYTOCHEMICAL LOCALIZATION; INHIBITORY PHOSPHOPROTEIN; DOPAMINE-RECEPTOR C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RP NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS NR 127 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 BN 0-12-540079-9 J9 PROG NUCLEIC ACID RE JI Prog. Nucl. Res. Molec. Biol. PY 2005 VL 79 BP 371 EP 404 DI 10.1016/S0079-6603(04)79008-X PG 34 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BCQ29 UT WOS:000230669200008 PM 16096033 ER PT S AU Levin, JG Guo, JH Rouzina, I Musier-Forsyth, K AF Levin, JG Guo, JH Rouzina, I Musier-Forsyth, K BE Moldave, K TI Nucleic acid chaperone activity of HIV-1 nucleocapsid protein: Critical role in reverse transcription and molecular mechanism SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 80 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; STRAND DNA-SYNTHESIS; PRIMER BINDING-SITE; ROUS-SARCOMA-VIRUS; RNASE-H ACTIVITY; STRONG-STOP DNA; DETECTED MAGNETIC-RESONANCE; TERMINAL ZINC-FINGER; TIME-RESOLVED FLUORESCENCE AB The HIV-1 nucleocapsid protein (NC) is a short, basic, nucleic-acid binding protein with two zinc finger domains, each containing the invariant CCHC metal ion binding motif. The mature protein (55 amino acid residues) is produced by proteolytic cleavage of the Gag precursor and is found in the interior of the virus particle, where it is tightly associated with genomic RNA. NC or the NC domain in Gag has multiple functions during the virus replication cycle, including genomic RNA packaging and virus assembly, primer placement on viral RNA, reverse transcription, and integration. Many of these functions rely on the nucleic acid chaperone activity of NC, i.e., the ability to catalyze nucleic acid conformational rearrangements that lead to the most thermodynamically stable structure. In this chapter, we focus on recent biochemical and biophysical studies that examine the nucleic acid chaperone function of HIV-1 NC and its critical role in facilitating specific and efficient reverse transcription. We describe the effect of NC on individual steps in viral DNA synthesis and summarize what is known about NC structure, NC nucleic acid binding properties, and the contribution of the zinc fingers to chaperone activity. In addition, we discuss new evidence that provides a model to explain the mechanism of NCs nucleic acid chaperone activity at the molecular level. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. RP Levin, JG (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM65056] NR 402 TC 243 Z9 247 U1 2 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 BN 0-12-540080-2 J9 PROG NUCLEIC ACID RE JI Prog. Nucl. Res. Molec. Biol. PY 2005 VL 80 BP 217 EP 286 DI 10.1016/S0079-6603(05)80006-6 PG 70 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDI39 UT WOS:000233598500006 PM 16164976 ER PT J AU SanGiovanni, JP Chew, EY AF SanGiovanni, JP Chew, EY TI The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; AGE-RELATED MACULOPATHY; TUMOR-NECROSIS-FACTOR; DIETARY FISH-OIL; PROTEIN-KINASE-C; PLATELET-ACTIVATING-FACTOR; NITRIC-OXIDE SYNTHASE; ROD OUTER SEGMENTS; CYTOSOLIC PHOSPHOLIPASE A(2); LOW-DENSITY-LIPOPROTEIN AB In this work we advance the hypothesis that omega-3 (omega-3) long-chain polyunsaturated fatty acids (LCPUFAs) exhibit cytoprotective and cytotherapeutic actions contributing to a number of anti-angiogenic and neuroprotective mechanisms within the retina. omega-3 LCPUFAs may modulate metabolic processes and attenuate effects of environmental exposures that activate molecules implicated in pathogenesis of vasoproliferative and neurodegenerative retinal diseases. These processes and exposures include ischemia, chronic light exposure, oxidative stress, inflammation, cellular signaling mechanisms, and aging. A number of bioactive molecules within the retina affect, and are effected by such conditions. These molecules operate within complex systems and include compounds classified as eicosanoids, angiogenic factors, matrix metalloproteinases, reactive oxygen species, cyclic nucleotides, neurotransmitters and neuromodulators, pro-inflammatory and immunoregulatory cytokines, and inflammatory phospholipids. We discuss the relationship of LCPUFAs with these bioactivators and bioactive compounds in the context of three blinding retinal diseases of public health significance that exhibit both vascular and neural pathology. How is omega-3 LCPUFA status related to retinal structure and function? Docosahexaenoic acid (DHA), a major dietary omega-3 LCPUFA, is also a major structural lipid of retinal photoreceptor outer segment membranes. Biophysical and biochemical properties of DHA may affect photoreceptor membrane function by altering permeability, fluidity, thickness, and lipid phase properties. Tissue DHA status affects retinal cell signaling mechanisms involved in phototransduction. DHA may operate in signaling cascades to enhance activation of membrane-bound retinal proteins and may also be involved in rhodopsin regeneration. Tissue DHA insufficiency is associated with alterations in retinal function. Visual processing deficits have been ameliorated with DHA supplementation in some cases. What evidence exists to suggest that LCPUFAs modulate factors and processes implicated in diseases of the vascular and neural retina? Tissue status of LCPUFAs is modifiable by and dependent upon dietary intake. Certain LCPUFAs are selectively accreted and efficiently conserved within the neural retina. On the most basic level, omega-3 LCPUFAs influence retinal cell gene expression, cellular differentiation, and cellular survival. DHA activates a number of nuclear hormone receptors that operate as transcription factors for molecules that modulate reduction-oxidation-sensitive and proinflammatory genes; these include the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and the retinoid X receptor. In the case of PPAR-alpha, this action is thought to prevent endothelial cell dysfunction and vascular remodeling through inhibition of: vascular smooth muscle cell proliferation, inducible nitric oxide synthase production, interleukin-1 induced cyclooxygenase (COX)-2 production, and thrombin-induced endothelin 1 production. Research on model systems demonstrates that omega-3 LCPUFAs also have the capacity to affect production and activation of angiogenic growth factors, arachidonic acid (AA)-based vasoregulatory eicosanoids, and MMPs. Eicosapentaenoic acid (EPA), a substrate for DHA, is the parent fatty acid for a family of eicosanoids that have the potential to affect AA-derived eicosanoids implicated in abnormal retinal neovascularization, vascular permeability, and inflammation. EPA depresses vascular endothelial growth factor (VEGF)-specific tyrosine kinase receptor activation and expression. VEGF plays an essential role in induction of: endothelial cell migration and proliferation, microvascular permeability, endothelial cell release of metalloproteinases and interstitial collagenases, and endothelial cell tube formation. The mechanism of VEGF receptor down-regulation is believed to occur at the tyrosine kinase nuclear factor-kappa B (NFkappaB). NFkappaB is a nuclear transcription factor that up-regulates COX-2 expression, intracellular adhesion molecule, thrombin, and nitric oxide synthase. All four factors are associated with vascular instability. COX-2 drives conversion of AA to a number angiogenic and proinflammatory eicosanoids. Our general conclusion is that there is consistent evidence to suggest that omega-3 LCPUFAs may act in a protective role against ischemia-, light-, oxygen-, inflammatory-, and age-associated pathology of the vascular and neural retina. Published by Elsevier Ltd. C1 NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP SanGiovanni, JP (reprint author), NEI, Div Epidemiol & Clin Res, NIH, 31 Ctr Dr,Bldg 31,Room 6A52,MSC 2510, Bethesda, MD 20892 USA. EM jpsangio@nei.nih.gov RI SanGiovanni, John Paul/A-7605-2008 FU Intramural NIH HHS [Z99 EY999999] NR 446 TC 337 Z9 367 U1 9 U2 54 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD JAN PY 2005 VL 24 IS 1 BP 87 EP 138 DI 10.1016/j.preteyeres.2004.06.002 PG 52 WC Ophthalmology SC Ophthalmology GA 881GW UT WOS:000225852400004 PM 15555528 ER PT J AU Luo, DL Sun, HL Lan, XM Xiao, RP Han, Q AF Luo, DL Sun, HL Lan, XM Xiao, RP Han, Q TI Direct coupling between arachidonic acid-induced Ca2+ release and Ca2+ entry in HEK293 cells SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE arachidonic acid; Ca2+ release; Ca2+ entry; Gd3+; coupling; isotetrandrine ID VASCULAR SMOOTH-MUSCLE; UNSATURATED FATTY-ACIDS; ENDOTHELIAL-CELLS; CALCIUM-RELEASE; MEMBRANE-FLUIDITY; ACTIVATION; MOBILIZATION; PATHWAYS; INFLUX; STORE AB Arachidonic acid (AA) modulates intracellular Ca2+ signaling via Ca2+ release or/and Ca2+ entry. However, the mechanism underlies either process is unknown; nor is it clear as to whether the two processes are mechanistically linked. By using Fura2/AM, we found that AA induced mobilization of internal Ca2+ store and an increment in Ca2+, Mn2+ and Ba2+ influx in HEK293 cells. The AA-mediated Ca2+ signaling was not due to AA metabolites, and insensitive to capacitative Ca2+ entry inhibitors. Interestingly, isotetrandrine and Gd3+ inhibited both AA-induced Ca2+ release and Ca2+ entry in a concentration-dependent manner without affecting Ca2+ discharge caused by carbachol, caffeine, or thapsigargin. Additionally, similar pattern of inhibition was observed with tetracaine treatment. More importantly, the three compounds exhibited almost equal potent inhibition of AA-initiated Ca2+ release as well as Ca2+ influx. Therefore, this study, for the first time, provides evidence for a direct coupling between AA-mediated Ca2+ release and Ca2+ entry. (c) 2004 Elsevier Inc. All rights reserved. C1 Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Luo, DL (reprint author), Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100083, Peoples R China. EM luod@grc.nia.nih.gov NR 33 TC 7 Z9 9 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-6980 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD JAN PY 2005 VL 75 IS 1-4 BP 141 EP 151 DI 10.1016/j.prostaglandins.2004.11.004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 907RP UT WOS:000227735900011 PM 15789621 ER PT J AU Hsing, AW Chokkalingam, AP AF Hsing, Ann W. Chokkalingam, Anand P. BE Chang, C TI EPIDEMIOLOGY OF PROSTATE CANCER SO PROSTATE CANCER: BASIC MECHANISMS AND THERAPEUTIC APPROACHES LA English DT Article; Book Chapter ID VITAMIN-D-RECEPTOR; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SOUTHERN EUROPEAN POPULATION; GLUTATHIONE-S-TRANSFERASES; CYP17 GENE POLYMORPHISM; MARINE FATTY-ACIDS; ANDROGEN RECEPTOR; JAPANESE POPULATION; SEQUENCE VARIANTS; AFRICAN-AMERICAN C1 [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Chokkalingam, Anand P.] Celera Diagnost LLC, Alameda, CA 94502 USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. NR 191 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-256-920-2 PY 2005 BP 315 EP 363 DI 10.1142/9789812569202_0014 D2 10.1142/9789812569202 PG 49 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA BWA68 UT WOS:000293276500015 ER PT J AU Lorick, KL Tsai, YC Yang, YL Weissman, AM AF Lorick, Kevin L. Tsai, Yien-Che Yang, Yili Weissman, Allan M. BE Mayer, J Ciechanover, A Rechsteiner, M TI RING Fingers and Relatives: Determinators of Protein Fate SO PROTEIN DEGRADATION: UBIQUITIN AND THE CHEMISTRY OF LIFE, VOL 1 LA English DT Article; Book Chapter ID UBIQUITIN LIGASE ACTIVITY; GROWTH-FACTOR RECEPTOR; N-END RULE; AMYOTROPHIC-LATERAL-SCLEROSIS; ZINC-BINDING DOMAIN; WILD-TYPE P53; RECESSIVE JUVENILE PARKINSONISM; PROTEASOME-MEDIATED DEGRADATION; MOLECULAR-WEIGHT COMPLEXES; RIBOSYLATION FACTOR DOMAIN C1 [Lorick, Kevin L.; Tsai, Yien-Che; Yang, Yili; Weissman, Allan M.] NCI Frederick, Frederick, MD 21702 USA. RP Lorick, KL (reprint author), NCI Frederick, Bldg 560,Room 22-103,1050 Boyles St, Frederick, MD 21702 USA. OI Tsai, Yien Che/0000-0001-9624-1092 NR 381 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-52760-586-6 PY 2005 BP 44 EP 101 PG 58 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BAE98 UT WOS:000303998400005 ER PT J AU Keskin, O Nussinov, R AF Keskin, O Nussinov, R TI Favorable scaffolds: proteins with different sequence, structure and function may associate in similar ways SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE interface motifs; protein architecture; protein-protein binding; protein-protein interaction; protein-protein interfaces ID CRYSTAL-STRUCTURE; RECOGNITION SITES; HOT-SPOTS; INTERFACES; RESIDUES; BINDING; CONSERVATION; RESOLUTION; STABILITY; ALIGNMENT AB Proteins with similar structures may have different functions. Here, using a non-redundant two-chain protein-protein interface dataset containing 103 clusters, we show that this paradigm extends to interfaces. Whereas usually similar interfaces are obtained from globally similar chains, this is not always the case. Remarkably, in some interface clusters, although the interfaces are similar, the overall structures and functions of the chains are different. Hence, our work suggests that different folds may combinatorially assemble to yield similar local interface motifs. The preference of different folds to associate in similar ways illustrates that the paradigm is universal, whether for single chains in folding or for protein-protein association in binding. We analyze and compare the two types of clusters. Type I, with similar interfaces, similar global structures and similar functions, is better packed, less planar, has larger total and non-polar buried surface areas, better complementarity and more backbone-backbone hydrogen bonds than 'Type II (similar interfaces, different global structures and different functions). The dataset clusters may provide rich data for protein-protein recognition, cellular networks and drug design. In particular, they should be useful in addressing the difficult question of what the favorable ways for proteins to interact are. C1 NCI, Basic Res Program, SIC Frederick Inc, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Sariyer Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Sariyer Istanbul, Turkey. 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, SIC Frederick Inc, Lab Expt & Computat Biol, Frederick, MD 21702 USA. EM okeskin@ku.edu.tr; ruthn@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 56 TC 45 Z9 45 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD JAN PY 2005 VL 18 IS 1 BP 11 EP 24 DI 10.1093/protein/gzh095 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 917GZ UT WOS:000228450200002 PM 15790576 ER PT J AU Podbilewicz, B Chernomordik, LV AF Podbilewicz, Benjamin Chernomordik, Leonid V. BE Tamm, LK TI Cell Fusion in Development and Disease SO PROTEIN-LIPID INTERACTIONS: FROM MEMBRANE DOMAINS TO CELLULAR NETWORKS LA English DT Article; Book Chapter ID NEMATODE CAENORHABDITIS-ELEGANS; INFLUENZA-VIRUS HEMAGGLUTININ; SPERM-EGG FUSION; HOX GENE LIN-39; C-ELEGANS; MYOBLAST FUSION; MEMBRANE-FUSION; PORE FORMATION; VULVAL INDUCTION; PLASMA-MEMBRANE C1 [Podbilewicz, Benjamin] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. [Chernomordik, Leonid V.] NICHHD, Lab Cellular & Mol Biophys, Sect Membrane Biol, NIH, Bethesda, MD 20892 USA. RP Podbilewicz, B (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel. NR 146 TC 3 Z9 3 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-52760-676-4 PY 2005 BP 221 EP 244 D2 10.1002/3527606769 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZT19 UT WOS:000302877400011 ER PT J AU Canagarajah, B Smith, WJ Hurley, JH AF Canagarajah, Bertram Smith, William J. Hurley, James H. BE Tamm, LK TI Structural Mechanisms of Allosteric Regulation by Membrane-binding Domains SO PROTEIN-LIPID INTERACTIONS: FROM MEMBRANE DOMAINS TO CELLULAR NETWORKS LA English DT Article; Book Chapter ID PROTEIN-KINASE-C; GUANINE-NUCLEOTIDE EXCHANGE; PLECKSTRIN HOMOLOGY DOMAIN; GTPASE-ACTIVATING PROTEIN; PHORBOL ESTER RECEPTORS; G-BETA-GAMMA; CRYSTAL-STRUCTURE; PHOSPHOINOSITIDE PHOSPHATASE; SUBCELLULAR-LOCALIZATION; 3-DIMENSIONAL STRUCTURE C1 [Canagarajah, Bertram; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Smith, William J.] NIDDK, Cell Biol & Metab Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Canagarajah, B (reprint author), NIDDK, Mol Biol Lab, NIH, US Dept HHS, 50 S Dr, Bethesda, MD 20892 USA. NR 67 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-52760-676-4 PY 2005 BP 423 EP 436 D2 10.1002/3527606769 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZT19 UT WOS:000302877400018 ER PT J AU Stan, G Brooks, BR Lorimer, GH Thirumalai, D AF Stan, G Brooks, BR Lorimer, GH Thirumalai, D TI Identifying natural substrates for chaperonins using a sequence-based approach SO PROTEIN SCIENCE LA English DT Article DE chaperonins; protein recognition; E. coli; yeast genomes ID IN-VIVO; CRYSTAL-STRUCTURE; GENOME SEQUENCE; PROTEINS; GROEL; POLYPEPTIDE; BINDING; RESIDUES; COMPLEX AB The Escherichia coli chaperonin machinery, GroEL, assists the folding of a number of proteins. We describe a sequence-based approach to identify the natural substrate proteins (SPs) for GroEL. Our method is based on the hypothesis that natural SPs are those that contain patterns of residues similar to those found in either GroES mobile loop and/or strongly binding peptide in complex with GroEL. The method is validated by comparing the predicted results with experimentally determined natural SPs for GroEL. We have searched for such patterns in five genomes. In the E. coli genome, we identify 1422 (about one-third) Sequences that are putative natural SPs. In Saccharomyces cerevisiae, 2885 (32%) of sequences can be natural substrates for Hsp60, which is the analog of GroEL. The precise number of natural SPs is shown to be a function of the number of contacts an SP makes with the apical domain (N-C) and the number of binding sites (N-B) in the oligomer with which it interacts. For known SPs for GroEL we find similar to4 < N-C < 5 and 2 less than or equal to N-B less than or equal to 4. A limited analysis of the predicted binding sequences shows that they do not adopt any preferred secondary structure. Our method also predicts the putative binding regions in the identified SPs. The results of our study show that a variety of SPs. associated with diverse functions, can interact with GroEL. C1 Univ Maryland, Inst Phys Sci & Technol, Biol Sci Program, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem, Biol Sci Program, College Pk, MD 20742 USA. NHLBI, Lab Computat Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biol Sci Program, College Pk, MD 20742 USA. EM thirum@glue.umd.edu FU NIGMS NIH HHS [1R01GM067851-01, R01 GM067851] NR 37 TC 14 Z9 14 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JAN PY 2005 VL 14 IS 1 BP 193 EP 201 DI 10.1110/ps.04933205 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 888OO UT WOS:000226384300021 PM 15576562 ER PT J AU Tress, M Tai, CH Wang, G Ezkurdia, I Lopez, G Valencia, A Lee, B Dunbrack, RL AF Tress, M Tai, CH Wang, G Ezkurdia, I Lopez, G Valencia, A Lee, B Dunbrack, RL TI Domain definition and target classification for CASP6 SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article; Proceedings Paper CT 6th Meeting on the Critical Assessment of Techniques for Protein Structure Prediction CY DEC 04-08, 2004 CL Gaeta, ITALY ID PROTEIN STRUCTURES; DATABASE; ALIGNMENTS; PARSER; PFAM AB Assessment of structure predictions in CASP6 was based on single domains isolated from experimentally determined structures, which were categorized into comparative modeling, fold recognition, and new fold targets. Domain definitions were defined upon visual examination of the structures with the aid of automated domain-parsing programs. Domain categorization was determined by comparison of the target structures with those in the Protein Data Bank at the time each target expired and a variety of sequence and structure-based methods to determine potential homologous relationships. C1 Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. CSIC, CNB, Prot Design Grp, Canto Blanco 28049, Spain. NIH, Mol Modeling & Bioinformat Sect, Lab Nol Modeling, Canc Res Ctr, Bethesda, MD 20892 USA. RP Dunbrack, RL (reprint author), Fox Chase Canc Ctr, Inst Canc Res, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM roland.dunbrack@fcce.edu OI Dunbrack, Roland/0000-0001-7674-6667 FU Intramural NIH HHS; NHGRI NIH HHS [R01-HG02302] NR 16 TC 15 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 2005 VL 61 SU 7 BP 8 EP 18 DI 10.1002/prot.20717 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 001SJ UT WOS:000234556300003 PM 16187342 ER PT J AU Vincent, JJ Tai, CH Sathyanarayana, BK Lee, B AF Vincent, JJ Tai, CH Sathyanarayana, BK Lee, B TI Assessment of CASP6 predictions for new and nearly new fold targets SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article; Proceedings Paper CT 6th Meeting on the Critical Assessment of Techniques for Protein Structure Prediction CY DEC 04-08, 2004 CL Gaeta, ITALY DE CASP6; protein structure prediction; New Fold prediction assessment ID ASTRAL COMPENDIUM; DATABASE; SEQUENCES; PROFILES; PFAM; SCOP AB This is a report of the assessment of the predictions made for the CASP6 protein structure prediction experiment conducted in 2004 in the New Fold (NF) category. There were nine protein domains that were judged to have new folds (NF) and 16 for which a similar structure was known but the sequence similarity was judged to be too low for them to be easily recognized (FR/A). We selected all NF targets and eight of the 16 FR/A targets judged to be at the borderline between NF and FR/A for evaluation in the NF category. A total of 165 prediction groups submitted over 7400 structural models for these targets. The quality of these models was evaluated using the GDT_TS scores of the structural similarity detection program LGA and by visual inspection of the top-scoring models. The best models submitted bore an overall similarity to the target structure for three or four of the nine NF targets and for all but one of the FR/A targets. High-scoring models for the NF targets were submitted by several different groups. When both the NF and FR/A targets were considered, Baker group dominated by submitting best models for seven of the 17 targets, but 14 other groups also managed to submit best models for one or more targets. C1 NIH, Mol Biol Lab, Canc Res Ctr, NCI, Bethesda, MD 20892 USA. RP Lee, B (reprint author), NIH, Mol Biol Lab, Canc Res Ctr, NCI, Bldg 37,Rm 5120,57 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. EM bk@nih.gov FU Intramural NIH HHS NR 23 TC 34 Z9 37 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 2005 VL 61 SU 7 BP 67 EP 83 DI 10.1002/prot.20722 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 001SJ UT WOS:000234556300008 PM 16187347 ER PT J AU Tai, CH Lee, WJ Vincent, JJ Lee, B AF Tai, CH Lee, WJ Vincent, JJ Lee, B TI Evaluation of domain prediction in CASP6 SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article; Proceedings Paper CT 6th Meeting on the Critical Assessment of Techniques for Protein Structure Prediction CY DEC 04-08, 2004 CL Gaeta, ITALY DE domain; prediction; assessment; protein structure; CASP6 ID SEQUENCE ALIGNMENTS; PROTEIN DOMAINS; BOUNDARIES; IDENTIFICATION; CLASSIFICATION; DATABASE; PARSER AB We present an analysis of the domain boundary prediction, a new category, in the sixth community-wide experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP6). There were 1011 predictions submitted for 63 targets. Each prediction was compared to the set of domains defined manually by visual inspection of the experimental structure. The comparison was scored using a new domain prediction scoring scheme. As the definition of a domain is subjective, many targets were assigned alternate definitions. For such targets, each prediction was compared with all different definitions and the best score was chosen. The predictors found it difficult to accurately predict domain boundaries when the target protein contained many domains or domains made of multiple sequence segments. The CBRC-DR (P0536) and Sternberg (P0237) groups were the most successful among human experts, while Baker-Rossettadom (P0353) and Baker-Robetta-Ginzu (P0421) did well among servers. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. RP Lee, B (reprint author), Bldg 37,Room 5120,37 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. EM bk@nih.gov NR 23 TC 22 Z9 25 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PY 2005 VL 61 SU 7 BP 183 EP 192 DI 10.1002/prot.20736 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 001SJ UT WOS:000234556300022 PM 16187361 ER PT J AU Amsellem, MS Arora, NK Hesse, BW Taplin, S AF Amsellem, MS Arora, NK Hesse, BW Taplin, S TI Experience with cancer: Relationship with cancer screening awareness, practice and recommendations from physicians SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S37 EP S38 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400068 ER PT J AU Finney, RLF Squiers, L AF Finney, RLF Squiers, L TI Information needs of family and friends of cancer patients: Evidence from the National Cancer Institute's Cancer Information Service SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S53 EP S53 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400099 ER PT J AU Finney, RLF Squiers, L Hesse, BW AF Finney, RLF Squiers, L Hesse, BW TI Cancer-relevant information needs of the general public: Evidence from the National Cancer Institute's Cancer Information Service SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S33 EP S33 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400060 ER PT J AU Wilkins, JN Majewska, MD Van Gorp, W Li, SH Hinken, C Plotkin, D Setoda, D AF Wilkins, JN Majewska, MD Van Gorp, W Li, SH Hinken, C Plotkin, D Setoda, D TI DHEAS and POMS measures identify cocaine dependence treatment outcome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE cocaine; profile of mood states; dehydroepiandrosterone sulphate; DHEA; DHEAS; dehydroepiandrosterone; cortisol; abstinent; relapsed; dropped out ID CORTICOTROPIN-RELEASING-FACTOR; DEHYDROEPIANDROSTERONE-SULFATE; MAJOR DEPRESSION; ABSTINENCE SYMPTOMATOLOGY; SMOKING-CESSATION; SALIVARY CORTISOL; DRUG-ADDICTION; PLASMA-LEVELS; FOLLOW-UP; ABUSERS AB Early attrition is a significant problem in the treatment of cocaine dependence, but it is unclear why some patients succeed in treatment while others relapse or drop out of treatment without a demonstrated relapse. The goal of this study was to determine whether baseline levels of select hormones, including the adrenal hormone and excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS), would distinguish between treatment outcome groups. Based on the literature, completion of 90 days of treatment was established as a key outcome variable. Methods: Quantitative urine levels of the cocaine metabolite benzoylecgonine (BE) and other substance of abuse analytes, plasma levels of DHEAS, DHEA, cortisol., and prolactin, and the profile of mood states (POMS) were serially measured in 38 mate cocaine-dependent (DSM-IV) patients and in 28 controls of similar gender and age over a six month study. Exclusion criteria for the patients and controls included Axis I mood, anxiety or psychotic disorders. The patients could not manifest substance dependence except to cocaine. The patients and controls received remuneration for urine and blood collection. Blood samples for hormone levels were obtained between 8 and 10 a.m. on days 1, 14 and 21 of a 21-day inpatient treatment program and throughout 6 months of outpatient study visits at 45-day intervals. Results: Attrition from treatment and study appointments occurred predominately at the junction between inpatient and outpatient programs. Forty percent of patients made the transition to outpatient treatment and remained abstinent and in treatment for a median of 103 days (ABST). Forty-two percent of patients dropped out of treatment during the inpatient stay or never returned after completing the inpatient program (DO) and 18% had a documented relapse either during, or within the first week after, the inpatient stay (REL). POMS total scores were elevated at treatment entry for both the ABST and DO groups. Plasma DHEAS levels in the DO patients were decreased compared to controls and increased in the ABST patients. POMS total scores for the REL patients at baseline were at control levels. Baseline cortisol levels were not statistically different between the outcome groups, though they were elevated for all cocaine patient groups. When treatment outcome was collapsed into whether patients completed (ABST) or did not complete 90 days of treatment (90N), ABST plasma DHEAS and cortisol. were significantly elevated compared to the 90N patients and controls across the first 3 weeks of cocaine withdrawal. Conclusions: At treatment entry, each of the three patient outcome groups was identified by Levels of circulating DHEAS and distressed mood. In the ABST patients, distressed mood during withdrawal may have been mitigated through antidepressant-like actions of enhanced endogenous DHEAS activity, thus contributing to improved abstinence and treatment retention. Patients, such as the DO group, with high levels of distressed mood at treatment entry and low DHEAS levels may benefit from adjunctive pharmacotherapy that targets DHEAS and POMS measures. Patients, such as the REL group, who tack distressed mood at treatment entry, may require intense application of motivational approaches plus residential treatment. (C) 2004 Elsevier Ltd. All rights reserved. C1 Cedars Sinai Med Ctr, Dept Psychiat, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Wilkins, JN (reprint author), Cedars Sinai Med Ctr, Dept Psychiat, 8730 Alden Dr,Room C-301, Los Angeles, CA 90048 USA. EM wilkinsj@cshs.org NR 69 TC 27 Z9 27 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN PY 2005 VL 30 IS 1 BP 18 EP 28 DI 10.1016/j.psyneuen.2004.04.006 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 858TL UT WOS:000224214700003 PM 15358439 ER PT J AU Blumenthal, TD Cuthbert, BN Filion, DL Hackley, S Lipp, OV Van Boxtel, A AF Blumenthal, TD Cuthbert, BN Filion, DL Hackley, S Lipp, OV Van Boxtel, A TI Committee report: Guidelines for human startle eyeblink electromyographic studies SO PSYCHOPHYSIOLOGY LA English DT Article DE startle; blink; electromyographic (EMG); human ID HUMAN BLINK REFLEX; INTEGRATOR TIME CONSTANT; PREPULSE INHIBITION; TEMPORAL SUMMATION; SURFACE ELECTROMYOGRAPHY; ACOUSTIC STARTLE; STIMULUS RISE; R3 COMPONENT; STIMULATION; RESPONSES AB The human startle response is a sensitive, noninvasive measure of central nervous system activity that is Currently used in a wide variety of research and clinical settings. In this article, we raise methodological issues and present recommendations for optimal methods of startle blink electromyographic (EMG) response elicitation, recording, quantification, and reporting. It is hoped that this report Will foster more methodological validity and reliability in research using the startle response, Lis well Lis increase the detail with which relevant methodology is reported in publications using this measure. C1 Wake Forest Univ, Dept Psychol, Winston Salem, NC 27109 USA. NIMH, Bethesda, MD 20892 USA. Univ Missouri, Dept Psychol, Kansas City, MO 64110 USA. Univ Missouri, Dept Psychol Sci, Columbia, MO USA. Univ Queensland, Sch Psychol, Brisbane, Qld, Australia. Tilburg Univ, Dept Psychol, NL-5000 LE Tilburg, Netherlands. RP Blumenthal, TD (reprint author), Wake Forest Univ, Dept Psychol, Winston Salem, NC 27109 USA. EM blumen@wfu.edu RI Lipp, Ottmar/A-1254-2007; van Boxtel, Anton/C-4002-2013 OI Lipp, Ottmar/0000-0001-6734-8608; FU NIMH NIH HHS [MH061614] NR 91 TC 475 Z9 480 U1 7 U2 46 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2005 VL 42 IS 1 BP 1 EP 15 DI 10.1111/j.1469-8986.2005.00271.x PG 15 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 904QX UT WOS:000227513900001 PM 15720576 ER PT J AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ TI Biodiversity: A continuing source of novel drug leads SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT Joint Meeting of 24th International Symposium on Chemistry of Natural Products/4th International Congress on Biodiversity CY JAN 26-31, 2004 CL Delhi, INDIA ID DIVERSITY-ORIENTED SYNTHESIS; BIOSYNTHETIC GENE-CLUSTER; MOLLUSK ELYSIA-RUFESCENS; NATURAL-PRODUCT; COMBINATORIAL LIBRARIES; PRIVILEGED STRUCTURES; POLYKETIDE SYNTHASES; SORANGIUM-CELLULOSUM; MICROBIAL DIVERSITY; CYTOTOXIC PEPTIDES AB Nature has been a source of medicinal agents for thousands of years and continues to be an abundant source of novel chemotypes and pharmacophores. With only 5 to 15% of the approximately 250 000 species of higher plants systematically investigated, and the potential of the marine environment barely tapped, these areas will remain a rich source of novel bioactive compounds. Less than 1% of bacterial and 5% of fungal species are currently known, and the potential of novel microbial sources, particularly those found in extreme environments, seems unbounded. To these natural sources can be added the potential to investigate the rational design of novel structure types within certain classes of microbial metabolites through genetic engineering. It is apparent that Nature can provide the novel chemical scaffolds for elaboration by combinatorial approaches (chemical and biochemical), thus leading to agents that have been optimized on the basis of their pharmacological activities. The proven natural product drug discovery track record, coupled with the continuing threat to biodiversity through the destruction of terrestrial and marine ecosystems and the current low number of new chemical entities in pharmaceutical industry pipelines, provides a compelling argument in favor of expanded multidisciplinary and international collaboration in the exploration of Nature as a source of novel leads for the development of drugs and other valuable bioactive agents. C1 NCI, Frederick Canc Res & Dev Ctr, Nat Prod Branch, Dev Therapeut Program,Fairview Ctr 206, Frederick, MD 21702 USA. RP Cragg, GM (reprint author), NCI, Frederick Canc Res & Dev Ctr, Nat Prod Branch, Dev Therapeut Program,Fairview Ctr 206, POB B, Frederick, MD 21702 USA. EM craggg@mail.nih.gov NR 104 TC 86 Z9 94 U1 4 U2 25 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD JAN PY 2005 VL 77 IS 1 BP 7 EP 24 DI 10.1351/pac200577010007 PG 18 WC Chemistry, Multidisciplinary SC Chemistry GA 900RS UT WOS:000227232600003 ER PT S AU Lanzagorta, M Uhlmann, JK AF Lanzagorta, M Uhlmann, JK BE Donkor, EJ Pirich, AR Brandt, HE TI Hybrid quantum computing: Semicloning for general database retrieval SO Quantum Information and Computation III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Quantum Information and Computation III CY MAR 29-30, 2005 CL Orlando, FL DE quantum computing; quantum algorithms; Grover's algorithm; quantum cloning; state estimation; computational geometry; databases; simulation; virtual reality; collision detection ID CLONING AB Quantum computing (QC) has become an important area of research in computer science because of its potential to provide more efficient algorithmic solutions to certain problems than are possible with classical computing (CC). In particular, QC is able to exploit the special properties of quantum superposition to achieve computational parallelism beyond what can be achieved with parallel CC computers. However, these special properties are not applicable for general computation. Therefore, we propose the use of "hybrid quantum computers" (HQCs) that combine both classical and quantum computing architectures in order to leverage the benefits of both. We demonstrate how an HQC can exploit quantum search to support general database operations more efficiently than is possible with CC. Our solution is based on new quantum results that are of independent significance to the field of quantum computing. More specifically, we demonstrate that the most restrictive implications of the quantum No-Cloning Theorem can be avoided through the use of semiclones. C1 NCI, Informat Syst, Bethesda, MD 20892 USA. RP Lanzagorta, M (reprint author), NCI, Informat Syst, Bethesda, MD 20892 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5800-7 J9 P SOC PHOTO-OPT INS PY 2005 VL 5815 BP 78 EP 86 DI 10.1117/12.602928 PG 9 WC Computer Science, Information Systems; Computer Science, Theory & Methods SC Computer Science GA BCW49 UT WOS:000231558600009 ER PT J AU Szajek, LP Meyer, W Plascjak, P Eckelman, WC AF Szajek, LP Meyer, W Plascjak, P Eckelman, WC TI Semi-remote production of [Cu-64]CuCl2 and preparation of high specific activity [Cu-64]Cu-ATSM for PET studies SO RADIOCHIMICA ACTA LA English DT Article DE Cu-64; ATSM; specific activity; PET imaging; tangential target; automation ID POSITRON-EMISSION-TOMOGRAPHY; EXCITATION-FUNCTIONS; NUCLEAR-REACTIONS; CU-ATSM; HYPOXIA; CU-64; CYCLOTRON; AGENT; RADIOTHERAPY; CANCER AB The PET radionuclide Cu-64 (t(1/2) = 12.7 h) can be easily produced utilizing the nuclear reaction Ni-64(p, n)Cu-64. A high Cu-64 production rate was obtained using high-purity enriched nickel metal on the internal tangential target of the CS-30 cyclotron. Radio-copper was isolated after column chromatography using a semi-remote apparatus. Use of reagents with little or no carrier copper yields high specific activity Cu-64 pharmaceuticals prepared from the isolated [Cu-64]CuCl2. [Cu-64]Cu-ATSM was prepared in greater than 1.21 &PLUSMN; 0.40 Ci/mmol (45 &PLUSMN; 15 GBq/mmol) at EOB. C1 NIH, Positron Emiss Tomog Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Szajek, LP (reprint author), NIH, Positron Emiss Tomog Dept, Warren G Magnuson Clin Ctr, 10 Ctr Dr, Bethesda, MD 20892 USA. EM ls140h@nih.gov NR 18 TC 34 Z9 34 U1 0 U2 5 PU R OLDENBOURG VERLAG PI MUNICH PA LEKTORAT MINT, POSTFACH 80 13 60, D-81613 MUNICH, GERMANY SN 0033-8230 J9 RADIOCHIM ACTA JI Radiochim. Acta PY 2005 VL 93 IS 4 BP 239 EP 244 DI 10.1524/ract.93.4.239.64070 PG 6 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 923RO UT WOS:000228927200009 ER PT J AU Carr, JJ Nelson, JC Wong, ND McNitt-Gray, M Arad, Y Jacobs, DR Sidney, S Bild, DE Williams, OD Detrano, RC AF Carr, JJ Nelson, JC Wong, ND McNitt-Gray, M Arad, Y Jacobs, DR Sidney, S Bild, DE Williams, OD Detrano, RC TI Calcified coronary artery plaque measurement with cardiac CT in population-based studies: Standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study SO RADIOLOGY LA English DT Article ID ELECTRON-BEAM CT; COMPUTED-TOMOGRAPHY; QUANTIFICATION; CALCIFICATION; HEART; CALCIUM; MOTION AB Calcified coronary artery plaque, measured at cardiac computed tomography (CT), is a predictor of cardiovascular disease and may play an increasing role in cardiovascular disease risk assessment. The Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study of the National Heart, Lung, and Blood Institute are population-based studies in which calcified coronary artery plaque was measured with electron-beam and multidetector row CT and a standardized protocol in 6814 (MESA) and 3044 (CARDIA study) participants. The studies were approved by the appropriate institutional review board from the study site or agency, and written informed consent was obtained from each participant. Participation in the CT examination was high, image quality was good, and agreement for the presence of calcified plaque was high (kappa = 0.92, MESA; kappa = 0.77, CARDIA study). Extremely high agreement was observed between and within CT image analysts for the presence (kappa > 0.90, all) and amount (intraclass correlation coefficients, >0.99) of calcified plaque. Measurement of calcified coronary artery plaque with cardiac CT is well accepted by participants and can be implemented with consistently high-quality results with a standardized protocol and trained personnel. If predictive value of calcified coronary artery plaque for cardiovascular events proves sufficient to justify screening a segment of the population, then a standardized cardiac CT protocol is feasible and will provide reproducible results for health care providers and the public. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Univ Washington, Dept Biostat, Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA 98195 USA. Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA USA. Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. Columbia Univ, Dept Clin Med, New York, NY USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Kaiser Permanente, Div Res, Oakland, CA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Harbor UCLA Res & Educ Inst, Los Angeles, CA USA. RP Carr, JJ (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. OI Carr, John/0000-0002-4398-8237 FU NCRR NIH HHS [M01 RR 07122]; NHLBI NIH HHS [N01 HC 95095, N01 HC 48047, N01 HC 48048, N01 HC 48049, N01 HC 48050, N01 HC 95159, N01 HC 95160, N01 HC 95161, N01 HC 95162, N01 HC 95163, N01 HC 95164, N01 HC 95165, N01 HC 95166, N01 HC 95167, N01 HC 95168, N01 HC 95169] NR 18 TC 449 Z9 450 U1 1 U2 13 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2005 VL 234 IS 1 BP 35 EP 43 DI 10.1148/radiol.2341040439 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 881JW UT WOS:000225864800009 PM 15618373 ER PT J AU Lakhani, NJ Lepper, ER Sparreboom, A Dahut, WL Venitz, J Figg, WD AF Lakhani, NJ Lepper, ER Sparreboom, A Dahut, WL Venitz, J Figg, WD TI Determination of 2-methoxyestradiol in human plasma, using liquid chromatography/tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article AB A liquid chromatography/tandern mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of 2-methoxyestradiol (2ME2) in human plasma. Sample pretreatment involved liquid-liquid extraction with ethyl acetate of 0.3-mL aliquots of plasma spiked with the internal standard, deuterated 2ME2 (2ME2-d5). Separation was achieved on a Zorbax Eclipse(®) C-18 column (2.1 x 50 mm, i.d., 5 μ m) at room temperature using a gradient elution with methanol and water at a flow rate of 0.25 mL/min. Detection was performed using atmospheric pressure chemical ionization MS/MS by monitoring the ion transitions from m/z 303.1&RARR; 136.8 (2ME2) and m/z 308.1&RARR; 138.8 (2ME2-d5). Calibration curves were linear in the concentration range of 1-100ng/ mL. The accuracy and precision values, obtained from three different sets of quality control. samples analyzed in quintuplicate on four separate occasions, ranged from 105-108% and from 3.62-5.68%, respectively. This assay was subsequently used for the determination of 2ME2 concentration in plasma of a patient with cancer after a single oral administration of 2ME2 at a dose of 2200 mg. Copyright © 2005 John Wiley & Sons, Ltd. C1 NCI, Canc Res Ctr, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), NCI, Canc Res Ctr, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 11 TC 27 Z9 27 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2005 VL 19 IS 9 BP 1176 EP 1182 DI 10.1002/rcm.1902 PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 923KF UT WOS:000228908100007 PM 15818726 ER PT J AU Novikov, A Caroff, M Della-Negra, S Depauw, J Fallavier, M Le Beyec, Y Pautrat, M Schultz, JA Tempez, A Woods, AS AF Novikov, A Caroff, M Della-Negra, S Depauw, J Fallavier, M Le Beyec, Y Pautrat, M Schultz, JA Tempez, A Woods, AS TI The Au-n cluster probe in secondary ion mass spectrometry: influence of the projectile size and energy on the desorption/ionization rate from biomolecular solids SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SLOW GOLD CLUSTERS; YIELDS; BEAMS; BOMBARDMENT; EMISSION; C-60(+); SILICON; IMPACT; TISSUE; FILMS AB A Au-Si liquid metal ion source which produces Au-n clusters over a large range of sizes was used to study the dependence of both the molecular ion desorption yield and the damage cross-section on the size (n = 1 to 400) and on the kinetic energy (E = 10 to 500 keV) of the clusters used to bombard bioorganic surfaces. Three pure peptides with molecular masses between 750 and 1200Da were used without matrix. [M+H](+) and [M+cation](+) ion emission yields were enhanced by as much as three orders of magnitude when bombarding with Au-400(4+) instead of monatomic Au+, yet very little damage was induced in the samples. A 100-fold increase in the molecular ion yield was observed when the incident energy of Au-9(+) was varied from 10 to 180 keV. Values of emission yields and damage cross-sections are presented as a function of cluster size and energy. The possibility to adjust both cluster size and energy, depending on the application, makes the analysis of biomolecules by secondary ion mass spectrometry an extremely powerful and flexible technique, particularly when combined with orthogonal time-of-flight mass spectrometry that then allows fast measurements using small primary ion beam currents. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Inst Phys Nucl, CNRS, F-91406 Orsay, France. Univ Paris 11, IBBMC, Equipe Endotoxines, CNR UMR 8619, F-91405 Orsay, France. Univ Lyon 1, Inst Phys Nucl Lyon, CNRS, F-69622 Villeurbanne, France. Ionwerks Inc, Houston, TX 77030 USA. NIDA, IRP, Baltimore, MD 21224 USA. RP Novikov, A (reprint author), Inst Phys Nucl, CNRS, IN2P3, F-91406 Orsay, France. EM novikov@ipno.in2p3.fr NR 34 TC 37 Z9 38 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2005 VL 19 IS 13 BP 1851 EP 1857 DI 10.1002/rcm.1995 PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 941GO UT WOS:000230203500011 PM 15945024 ER PT S AU Parham, F Portier, C AF Parham, Fred Portier, Christopher BE Edler, L Kitsos, CP TI Benchmark Dose Approach SO RECENT ADVANCES IN QUANTITATIVE METHODS IN CANCER AND HUMAN HEALTH RISK ASSESSMENT SE Wiley Series in Probability and Statistics LA English DT Article; Book Chapter C1 [Parham, Fred; Portier, Christopher] NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Parham, F (reprint author), NIEHS, Environm Toxicol Program, MD A3-06,POB 12233, Res Triangle Pk, NC 27709 USA. EM parham@niehs.nih.gov; portier@niehs.nih.gov NR 0 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 1940-6517 BN 978-0-47085-770-0 J9 WILEY SER PROBAB ST PY 2005 BP 239 EP 254 D2 10.1002/0470857706 PG 16 WC Oncology; Mathematical & Computational Biology; Public, Environmental & Occupational Health SC Oncology; Mathematical & Computational Biology; Public, Environmental & Occupational Health GA BZH99 UT WOS:000301664500020 ER PT S AU Przytycka, T Davis, G Song, N Durand, D AF Przytycka, T Davis, G Song, N Durand, D BE Miyano, S Mesirov, J Kasif, S Istrail, S Pevzner, P Waterman, M TI Graph theoretical insights into evolution of multidomain proteins SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 9th Annual International Conference on Research in Computational Molecular Biology (RECOMB 2005) CY MAY 14-18, 2005 CL Cambridge, MA SP Broad Inst MIT & Harvard, Boston Univ Ctr Adv Geonom Technol ID GENOME; SEQUENCE; FAMILIES; CLASSIFICATION; NETWORKS; KINASES AB We study properties of multidomain proteins from a graph theoretical perspective. In particular, we demonstrate connections between properties of the domain overlap graph and certain variants of Dollo parsimony models. We apply our graph theoretical results to address several interrelated questions: do proteins acquire new domains infrequently, or often enough that the same combinations of domains will be created repeatedly through independent events? Once domain architectures are created, do they persist? In other words, is the existence of ancestral proteins with domain compositions not observed in contemporary proteins unlikely? Our experimental results indicate that independent merges of domain pairs are not uncommon in large super-families. C1 NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20894 USA. Carnegie Mellon Univ, Program Computat Org & Soc, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. RP Przytycka, T (reprint author), NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20894 USA. EM przytyck@mail.nih.gov; durand@cmu.edu NR 34 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-25866-3 J9 LECT NOTES COMPUT SC PY 2005 VL 3500 BP 311 EP 325 PG 15 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Biochemistry & Molecular Biology; Computer Science GA BCK44 UT WOS:000229741100024 ER PT J AU Park, KJ Hwang, SC Sheen, SS Oh, YJ Han, JH Lee, KB AF Park, KJ Hwang, SC Sheen, SS Oh, YJ Han, JH Lee, KB TI Expression of matrix metalloproteinase-9 in pleural effusions of tuberculosis and lung cancer SO RESPIRATION LA English DT Article DE matrix metalloproteinase-9; tissue inhibitors of matrix metalloproteinase-1; tuberculous pleural effusion; malignant pleural effusion; lung cancer ID NECROSIS-FACTOR-ALPHA; HUMAN MONOCYTIC CELLS; MATRIX METALLOPROTEINASES; MYCOBACTERIUM-TUBERCULOSIS; MALIGNANT EFFUSIONS; GRANULOMA-FORMATION; 92-KDA GELATINASE; TISSUE INHIBITORS; TUMOR PROGRESSION; INTERFERON-GAMMA AB Background: Matrix metalloproteinase (MMP)-9 has been implicated in the development of pleural effusions. Objectives: The aim of this study was to assess the expression of MMP-9 in pleural effusions of tuberculosis, lung cancer and transudates. Methods: Ninety-one patients ( 37 tuberculous pleural effusions, 42 malignant pleural effusions of lung cancer and 12 transudates) were included. Concentrations of pleural fluid MMP-9 and tissue inhibitors of matrix metalloproteinase ( TIMP)1 were determined by immunoassay. We also investigated the cellular localization of MMP-9 and TIMP-1 by reverse-transcriptase polymerase chain reaction on lymphocytes from pleural effusions and by immunohistochemical analysis of pleural tissues. Results: Pleural fluid MMP-9 levels, MMP-9/total protein and MMP-9/TIMP-1 ratios were significantly higher in tuberculous pleural effusions, whilst TIMP-1 levels were similar in the three groups. MMP-9 levels positively correlated with TIMP-1 and lactate dehydrogenase levels, and negatively with pH and glucose levels in pleural effusions. MMP-9 mRNA expression in lymphocytes tended to be higher in malignant pleural effusions of lung cancer than in the other groups without reaching statistical significance. The strongest immunoreactivity for MMP-9 was observed in epithelioid cells of tuberculous pleural tissues. Much lower levels of MMP-9 expression were found in tumor cells of pleural tissues. Conclusions: MMP-9 is increased in tuberculous pleural effusions compared with transudates and malignant pleural effusions of lung cancer and is produced predominantly by epithelioid cells in the granulomas of tuberculous pleural tissues. Copyright (C) 2005 S. Karger AG, Basel. C1 Ajou Univ, Sch Med, Dept Pulm & Crit Care Med, Suwon 441749, South Korea. Ajou Univ, Sch Med, Dept Pathol, Suwon 441749, South Korea. RP Park, KJ (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 50, Bethesda, MD 20892 USA. EM parkk2@mail.nih.gov OI Hwang, Sung Chul/0000-0003-2401-619X NR 46 TC 31 Z9 35 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 J9 RESPIRATION JI Respiration PY 2005 VL 72 IS 2 BP 166 EP 175 DI 10.1159/000084048 PG 10 WC Respiratory System SC Respiratory System GA 917DE UT WOS:000228435400010 PM 15824527 ER PT J AU Jang, SH You, SH Kwon, YH Hallett, M Lee, MY Ahn, SH AF Jang, SH You, SH Kwon, YH Hallett, M Lee, MY Ahn, SH TI Cortical reorganization associated lower extremity motor recovery as evidenced by functional MRI and diffusion tensor tractography in a stroke patient SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE functional MRI; stroke; cortical reorganization; lower extremity motor recovery; diffusion tensor MRI ID TRACKING; FMRI AB Purpose: Recovery mechanisms supporting upper extremity motor recovery following stroke are well established, but cortical mechanism associated with lower extremity motor recovery is unknown. The aim of this study was to assess cortical reorganization associated with lower extremity motor recovery in a hemiparetic patient. Methods: Six control subjects and a 17 year-old woman with left intracerebral hemorrhage due to an arterio-venous malformation rupture were evaluated. The motor function of the paretic (left) hip and knee had recovered slowly to the extent of her being able to overcome gravity for 10 months after the onset of stroke. However, her paretic upper extremity showed no significant motor recovery. Blood oxygertation level dependent (BOLD) functional MRI at 1.5 Tesla was used to determine the acutual location of cortical activation in the predefined regions of interest. Concurrently, Diffusion Tensor Imaging (DTI) in combination with a novel 3D-fiber reconstruction algorithm was utilized to investigate the pattern of the corticospinal pathway connectivity between the areas of the motor stream. All subjects' body parts were secured in the scanner and performed a sequential knee flexion-extension with a predetermined angle of 0-60 degrees at 0.5 Hz. Results: Controls showed anticipated activation in the contralateral sensorimotor cortex (SM1) and the descending corticospinal fibers stemming from motor cortex. In contrast to control normal Subjects, the stroke patient showed fMRI activation only in the unaffected (right) primary SM1 during either paretic or nonparetic knee movements. DTT fiber tracing data showed that the corticospinal tract fibers were found only in the unaffected hemisphere but not in the affected hemisphere. C1 Hampton Univ, Phys Therapy Program, Hampton, VA 23668 USA. Yeungnam Univ, Sch Med, Dept Phys Med & Rehabil, Namku, Taegu 705717, South Korea. NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. Daegu Univ, Dept Phys Therapy, Grad Sch Rehabil Sci, Taegu 705717, South Korea. RP You, SH (reprint author), Hampton Univ, Phys Therapy Program, Phoenix Hall 219B, Hampton, VA 23668 USA. NR 11 TC 45 Z9 54 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2005 VL 23 IS 5-6 BP 325 EP 329 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 007HS UT WOS:000234960200007 PM 16477094 ER PT J AU Tang, J Tsilou, E Caruso, RC Rubin, B Gahl, WA AF Tang, J Tsilou, E Caruso, RC Rubin, B Gahl, WA TI Bilateral staphylomas in a patient with Hermansky-Pudlak syndrome SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Editorial Material DE Hermansky-Pudlak syndrome; staphyloma; HPS-1 gene; iris transillumination C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Tang, J (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bldg 10,Room 10S229,10 Ctr Dr, Bethesda, MD 20892 USA. EM tangjo@nei.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JAN PY 2005 VL 25 IS 1 BP 99 EP 100 DI 10.1097/00006982-200501000-00019 PG 2 WC Ophthalmology SC Ophthalmology GA 891OG UT WOS:000226589800019 PM 15655453 ER PT J AU Beer, B Cummins, J Reichelderfer, P Lackman-Smith, C AF Beer, Brigitte Cummins, James Reichelderfer, Patricia Lackman-Smith, Carol TI Testing candidate topical microbicides - Distinguishing toxicity from efficacy in preclinical testing SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Beer, Brigitte; Cummins, James; Lackman-Smith, Carol] Southern Res, Frederick, MD USA. [Reichelderfer, Patricia] NICHD, NIH, Bethesda, MD USA. EM beer@sri.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S92 DI 10.1186/1742-4690-2-S1-S92 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600171 ER PT J AU Belyakov, IM Kuznetsov, VA Kelsall, B Klinman, D Moniuszko, M Lemon, M Markham, PD Pal, R Clements, JD Lewis, MG Strober, W Franchini, G Berzofsky, JA AF Belyakov, Igor M. Kuznetsov, Vladimir A. Kelsall, Brian Klinman, Dennis Moniuszko, Marcin Lemon, Michael Markham, Phillip D. Pal, Ranajit Clements, John D. Lewis, Mark G. Strober, Warren Franchini, Genoveffa Berzofsky, Jay A. TI Can vaccine-induced mucosal high avidity CD8+CTL delay AIDS-viral dissemination from mucosa? SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Belyakov, Igor M.; Moniuszko, Marcin; Lemon, Michael; Franchini, Genoveffa; Berzofsky, Jay A.] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Kuznetsov, Vladimir A.] Genome Inst Singapore, Div Informat & Math Sci, Singapore 138672, Singapore. [Strober, Warren] NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. [Klinman, Dennis] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Markham, Phillip D.; Pal, Ranajit] Adv BioSci Labs Inc, Kensington, MD 20895 USA. [Clements, John D.] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA. [Lewis, Mark G.] So Res Inst, Frederick, MD USA. EM berzofsk@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S100 DI 10.1186/1742-4690-2-S1-S100 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600179 ER PT J AU Blumenthal, R Finnegan, CM Viard, M Rawat, SS Puri, A AF Blumenthal, Robert Finnegan, Catherine M. Viard, Mathias Rawat, Satinder S. Puri, Anu TI The cell biology of HIV-1 entry SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Blumenthal, Robert; Finnegan, Catherine M.; Viard, Mathias; Rawat, Satinder S.; Puri, Anu] NCI Frederick, LECB, CCR, NIH, Frederick, MD USA. EM blumen@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S137 DI 10.1186/1742-4690-2-S1-S137 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600203 ER PT J AU Buonaguro, L Tornesello, ML Arico, E Marincola, FM Lewis-Kamin, R Gallo, RC Lewis, GK Buonaguro, FM AF Buonaguro, L. Tornesello, M. L. Arico, E. Marincola, F. M. Lewis-Kamin, R. Gallo, R. C. Lewis, G. K. Buonaguro, F. M. TI Baculovirus-derived HIV-1 virus-like particles (VLP) activate dendritic cells and are cross-presented to induce in vitro T-cell response SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] INT G Pascale, Viral Oncol & AIDS Ref Ctr, Naples, Italy. [Arico, E.; Marincola, F. M.] NIH, Immunogen Lab, Dept Transf Med, Bethesda, MD USA. [Buonaguro, L.; Lewis-Kamin, R.; Gallo, R. C.; Lewis, G. K.] UMBI, IHV, Div Vaccine Res, Baltimore, MD USA. [Lewis-Kamin, R.; Lewis, G. K.] UMB, Dept Microbiol Immunol, Baltimore, MD USA. EM buonoguro@umbi.umd.edu RI Tornesello, Maria Lina/A-1564-2009 OI Tornesello, Maria Lina/0000-0002-3523-3264 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S70 DI 10.1186/1742-4690-2-S1-S70 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600159 ER PT J AU Dimitrov, DS AF Dimitrov, Dimiter S. TI Cross-reactive HIV-1 neutralizing human monoclonal antibodies with unique features: Structural mimicry of CD4, conformational flexibility, lack of light chain SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, NIH, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S63 DI 10.1186/1742-4690-2-S1-S63 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600154 ER PT J AU Fauci, AS AF Fauci, Anthony S. TI Pathogenic mechanisms of HIV disease: The role of viral replication and immune activation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Fauci, Anthony S.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S109 DI 10.1186/1742-4690-2-S1-S109 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600185 ER PT J AU Felber, BK AF Felber, Barbara K. TI Mechanisms contributing to control of viremia SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Felber, Barbara K.] Natl Canc Inst, Frederick, MD USA. EM felber@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S145 DI 10.1186/1742-4690-2-S1-S145 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600210 ER PT J AU Graham, BS AF Graham, Barney S. TI Clinical trials of DNA and recombinant adenovector (rAd) vaccines for HIV SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S61 DI 10.1186/1742-4690-2-S1-S61 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600152 ER PT J AU Grossman, Z AF Grossman, Zvi TI HIV replication, immune activation, and CD4 depletion: What the virus spares is as significant as what it destroys SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Grossman, Zvi] Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. [Grossman, Zvi] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S148 DI 10.1186/1742-4690-2-S1-S148 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600212 ER PT J AU Gupta, N Desmezieres, E Vassell, R He, Y Wingfield, P Weiss, CD AF Gupta, Nidhi Desmezieres, Emmanuel Vassell, Russell He, Yong Wingfield, Paul Weiss, Carol D. TI HIV escape from peptide fusion inhibitors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Gupta, Nidhi; Desmezieres, Emmanuel; Vassell, Russell; He, Yong; Weiss, Carol D.] US FDA, CBER, Bethesda, MD 20892 USA. [Wingfield, Paul] NIAMS, NIH, Bethesda, MD 20892 USA. EM gupta@ncber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR P34 DI 10.1186/1742-4690-2-S1-P34 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600027 ER PT J AU Harris, A Belnap, D Watts, N Conway, J Cheng, N Stahl, S Wingfield, P Steven, A AF Harris, Audray Belnap, David Watts, Norman Conway, James Cheng, Naiqian Stahl, Stephen Wingfield, Paul Steven, Alasdair TI Antigenic diversity of the hepatitis B virus capsid SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Harris, Audray; Watts, Norman; Cheng, Naiqian; Stahl, Stephen; Wingfield, Paul; Steven, Alasdair] NIAMS, NIH, Bethesda, MD 20892 USA. [Belnap, David] Brigham Young Univ, Provo, UT 84602 USA. [Conway, James] Univ Pittsburgh, Pittsburgh, PA 15261 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR P35 DI 10.1186/1742-4690-2-S1-P35 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600028 ER PT J AU Lagenaur, L Liu, XW Simpson, DA Essenmacher, K Parker, C Chang, CH Tsai, D Rao, S Hamer, D Parks, TP Lee, PP Xu, Q AF Lagenaur, Laurel Liu, Xiaowen Simpson, David A. Essenmacher, Kirsten Parker, Courtney Chang, Chia-Hwa Tsai, Daniel Rao, Srinivas Hamer, Dean Parks, Thomas P. Lee, Peter P. Xu, Qiang TI Development of vaginal lactobacilli for mucosal delivery of a topical microbicide, cyanovirin-N (CV-N) SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Lagenaur, Laurel; Liu, Xiaowen; Simpson, David A.; Essenmacher, Kirsten; Parker, Courtney; Chang, Chia-Hwa; Tsai, Daniel; Parks, Thomas P.; Lee, Peter P.; Xu, Qiang] Osel Inc, Santa Clara, CA 95054 USA. [Rao, Srinivas] NIH, Lab Anim Med, VRC, Bethesda, MD 20892 USA. [Hamer, Dean] NCI, NIH, Bethesda, MD 20892 USA. [Lee, Peter P.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. EM llagenaur@oselinc.com NR 0 TC 2 Z9 2 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S93 DI 10.1186/1742-4690-2-S1-S93 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600172 ER PT J AU Margolis, L AF Margolis, Leonid TI Mechanisms of HIV suppression by various microbes in human lymphoid tissue SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Margolis, Leonid] NICHHD, Sect Intercellular Interact, Bethesda, MD 20892 USA. EM margolis@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S8 DI 10.1186/1742-4690-2-S1-S8 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600120 ER PT J AU Melar, M Ott, D Hope, TJ AF Melar, Marta Ott, David Hope, Thomas J. TI Coreceptor dependent signaling in individual primary resting CD4+T-cells mediated by low levels of HIV binding SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Melar, Marta; Hope, Thomas J.] Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA. [Ott, David] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. EM thope@northwestern.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S3 DI 10.1186/1742-4690-2-S1-S3 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600115 ER PT J AU Nabel, GJ AF Nabel, G. J. TI Rational design of AIDS vaccines SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Nabel, G. J.] NIAID, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. EM gnabel@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S28 DI 10.1186/1742-4690-2-S1-S28 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600130 ER PT J AU Pavlakis, GN AF Pavlakis, George N. TI Long-lasting decrease in viremia in chronically SIVmac251-infected macaques after therapeutic immunization with combinations of DNA vectors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Pavlakis, George N.] NCI, Frederick, MD USA. EM pavlakis@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S140 DI 10.1186/1742-4690-2-S1-S140 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600206 ER PT J AU Peng, B Malkevitch, N Patterson, LJ Gomez-Roman, VR Venzon, D Florese, R Srivastava, I Barnett, SW Robert-Guroff, M AF Peng, Bo Malkevitch, Nina Patterson, L. Jean Gomez-Roman, V. Raul Venzon, David Florese, Ruth Srivastava, Indresh Barnett, Susan W. Robert-Guroff, Marjorie TI Prime-boost AIDS vaccine strategies based on replication-competent adenovirus recombinants SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Peng, Bo; Malkevitch, Nina; Patterson, L. Jean; Florese, Ruth; Robert-Guroff, Marjorie] Vaccine Branch, Emeryville, CA 94608 USA. [Gomez-Roman, V. Raul; Srivastava, Indresh; Barnett, Susan W.] Chiron Corp, Emeryville, CA 94608 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S64 DI 10.1186/1742-4690-2-S1-S64 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600155 ER PT J AU Xu, Q Lagenaur, L Liu, XW Simpson, D Essenmacher, K Parker, C Chang, CH Tsai, D Rao, S Hamer, D Parks, T Lee, P AF Xu, Qiang Lagenaur, Laurel Liu, Xiaowen Simpson, David Essenmacher, Kirsten Parker, Courtney Chang, Chia-Hwa Tsai, Daniel Rao, Srinivas Hamer, Dean Parks, Thomas Lee, Peter TI Vaginal lactobacilli for mucosal delivery of the anti-HIV microbicide, cyanovirin-N (CV-N) SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Xu, Qiang; Lagenaur, Laurel; Liu, Xiaowen; Simpson, David; Essenmacher, Kirsten; Parker, Courtney; Chang, Chia-Hwa; Tsai, Daniel; Parks, Thomas; Lee, Peter] Osel Inc, Santa Clara, CA 95054 USA. [Rao, Srinivas] NIH, Lab Anim Med, VRC, Bethesda, MD 20892 USA. [Hamer, Dean] NCI, NIH, Bethesda, MD 20892 USA. EM qxu@oselinc.com NR 0 TC 1 Z9 1 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S87 DI 10.1186/1742-4690-2-S1-S87 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600167 ER PT J AU Zhang, MY Vu, B Choudhry, V Sidorov, I Tenev, V Dimitrov, DS AF Zhang, Mei-Yun Vu, Bang Choudhry, Vidita Sidorov, Igor Tenev, Vladimir Dimitrov, Dimiter S. TI Cross-reactive anti-gp41 HIV-1 neutralizing human monoclonal antibodies selected by competitive panning against gp140 - an update SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhang, Mei-Yun; Vu, Bang; Choudhry, Vidita; Sidorov, Igor; Tenev, Vladimir; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, LECB, CCR, Frederick, MD 21702 USA. [Zhang, Mei-Yun] NCI, SAIC Frederick Inc, BRP, Frederick, MD 21702 USA. EM vub@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR P102 DI 10.1186/1742-4690-2-S1-P102 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600074 ER PT J AU Zhang, MY Chakraborti, S Prabakaran, P Choudhry, V Dimitrov, DS AF Zhang, Mei-Yun Chakraborti, Samitabh Prabakaran, Ponraj Choudhry, Vidita Dimitrov, Dimiter S. TI A unique cross-reactive HIV-1 neutralizing CD4i human monoclonal antibody containing only a heavy chain: Engineering a domain antibody and improvement of its potency and solubility SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhang, Mei-Yun; Chakraborti, Samitabh; Prabakaran, Ponraj; Choudhry, Vidita; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, LECB, CCR,NIH, Frederick, MD 21702 USA. [Zhang, Mei-Yun] NCI, SAIC Frederick Inc, BRP, Frederick, MD 21702 USA. EM schakraborti@ncifcrf.gov RI Ponraj, Prabakaran/D-6325-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR P22 DI 10.1186/1742-4690-2-S1-P22 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600017 ER PT J AU Zhu, JF Yamane, H Paul, WE AF Zhu, Jinfang Yamane, Hidehiro Paul, William E. TI GATA3 and STAT5 - Critical inducers of the Th2 fate SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhu, Jinfang; Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM wepaul@nih.gov RI Zhu, Jinfang/B-7574-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S16 DI 10.1186/1742-4690-2-S1-S16 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600126 ER PT S AU Roth, GS Lane, MA Ingram, DK AF Roth, GS Lane, MA Ingram, DK BE Pierpaoli, W TI Caloric restriction mimetics - The next phase SO REVERSAL OF AGING: RESETTING THE PINEAL CLOCK SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 4th Stromboli Conference on Aging and Cancer CY JUN 06-11, 2005 CL Sicily, ITALY SP Walter Pierpaoli Fdn Life Sci DE nutrition; longevity; glucose; glycolysis; insulin; 2-deoxyglucose ID PROTECTS HIPPOCAMPAL-NEURONS; OXIDATIVE INJURY; RHESUS-MONKEYS; PPAR-GAMMA; LIFE-SPAN; LONGEVITY; PROTEINS; HUMANS; MICE; INVOLVEMENT AB Calorie restriction (CR) mimetics are agents or strategies that can mimic the beneficial health-promoting and anti-aging effects of CR, the only intervention conclusively shown to slow aging and maintain health and vitality across the phylogenetic spectrum. Our lead compound, developed at the National Institute on Aging, was 2-deoxyglucose, an analogue of the native sugar, that acted as a glycolytic inhibitor, having limited metabolism and actually reducing overall energy flow-analogous to CR. This agent reduced insulin levels and body temperature of rats, similar to the physiological effects of CR, but toxicity was noted in long-term studies, which apparently prevented life-span extension. We previously demonstrated that lower insulin and body temperature (as well as maintenance of dehydroepiandrosterone levels) correlate with longevity in non-CR humans. The recent work of other investigators shows that humans subjected to short-term CR also have lower insulin and body temperature. Obviously, longer-term CR is extremely difficult to maintain; hence, the need for CR mimetics. The next phase of calorie restriction studies includes basic investigations as well as possible clinical trials of a number of candidate CR mimetics, ranging from glycolytic inhibitors to lipid-regulating agents to antioxidants and specific gene modulators. The scope of these ongoing studies in various laboratories, as well as their practical implications, are reviewed and analyzed here. C1 NIA, Lab Expt Gerontol, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. GeroSci Inc, Pylesville, MD 21132 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Gerontol Res Ctr, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM geor@iximed.com NR 37 TC 39 Z9 41 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-602-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1057 BP 365 EP 371 DI 10.1136/annals.1356.027 PG 7 WC Geriatrics & Gerontology; Multidisciplinary Sciences SC Geriatrics & Gerontology; Science & Technology - Other Topics GA BDY45 UT WOS:000236116800023 PM 16399906 ER PT J AU Santos, N Hoshino, Y AF Santos, N Hoshino, Y TI Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID GROUP-A ROTAVIRUS; LONG RNA ELECTROPHEROTYPE; SUBGROUP-I SPECIFICITY; REVERSE TRANSCRIPTION-PCR; SOUTH-AFRICAN CHILDREN; CAPSID PROTEIN VP7; RIO-DE-JANEIRO; ACUTE DIARRHEA; SEROTYPE G9; UNITED-STATES AB A safe and effective rotavirus vaccine is urgently needed, particularly in developing countries. Critical to vaccine development and implementation is a knowledge base concerning the epidemiology of rotavirus G and P genotypes throughout the world. The temporal and geographical distribution of human rotavirus G and P types was reviewed by analysing a total of 45571 strains collected globally from 124 studies reported from 52 countries on five continents published between 1989 and 2004. Four common G types (G1, G2, G3 and G4) in conjunction with P[8] or P[4] represented over 88% of the strains analysed worldwide. In addition, serotype G9 viruses associated with P(31 or P[6] were shown to have emerged as the fourth globally important G type with the relative frequency of 4.1%. When the global G and/or P type distributions were divided into five continents/subcontinents, several characteristic features emerged. For example, the P[8]G1 represented over 70% of rotavirus infections in North America, Europe and Australia, but only about 30% of the infections in South America and Asia, and 23% in Africa. In addition, in Africa (i) the relative frequency of G8 was as high as that of the globally common G3 or G4, (ii) P[6] represented almost one-third of all P types identified and (iii) 27% of the infections were associated with rotavirus strains bearing unusual combinations such as P[6]G8 or P[4]G8. Furthermore, in South America, uncommon G5 virus appeared to increase its epidemiological importance among children with diarrhea. Such findings have (i) confirmed the importance of continued active rotavirus strain surveillance in a variety of geographical settings and (ii) provided important considerations for the development and implementation of an effective rotavirus vaccine (e.g. a geographical P-G type adjustment in the formulation of next generation multivalent vaccines). Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, Cidade Univ, BR-21941590 Rio De Janeiro, RJ, Brazil. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Dept Virol, Inst Microbiol, Cidade Univ, CCS-Bl 1,Ilha Fundao, BR-21941590 Rio De Janeiro, RJ, Brazil. EM nsantos@micro.ufrj.br RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 241 TC 756 Z9 793 U1 6 U2 36 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD JAN-FEB PY 2005 VL 15 IS 1 BP 29 EP 56 DI 10.1002/rmv.448 PG 28 WC Virology SC Virology GA 886YV UT WOS:000226270100004 PM 15484186 ER PT J AU Alperovitch, A Kasir, J Kimchi-Sarfaty, C Rahamimoff, H AF Alperovitch, A Kasir, J Kimchi-Sarfaty, C Rahamimoff, H TI Transport activity and surface expression of the Na+-Ca2+ exchanger NCX2 and NCX3 are inhibited by cyclosporin A SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91010 Jerusalem, Israel. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S1 EP S1 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100004 ER PT J AU Spivak-Pohis, I Mandel, S Loh, YP Gozes, I AF Spivak-Pohis, I Mandel, S Loh, YP Gozes, I TI Constitutive and regulated secretion of activity-dependent neuroprotective protein (ADNP)-like protein sequences SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NICHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S61 EP S61 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100259 ER PT J AU Winetraub, Y Holroyd, T Japee, S Ungerleider, LG Hendler, T AF Winetraub, Y Holroyd, T Japee, S Ungerleider, LG Hendler, T TI Emotional modulation of awareness in the human brain: Complementary evidence in fMRI & MEG SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 Tel Aviv Univ, Wohl Inst Adv Imaging, Tel Aviv Sourasky Med Ctr, Funct Brain Imaging Unit, Tel Aviv, Israel. Tel Aviv Univ, LE G Inst Human Brain Mapping, Tel Aviv, Israel. NIMH, MEG Core Facil, Bethesda, MD USA. NIMH, Lab Brain & Cognit, Bethesda, MD USA. Tel Aviv Univ, Fac Social Sci, Tel Aviv, Israel. Tel Aviv Univ, Fac Med, Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S68 EP S68 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100285 ER PT J AU Zohar, O Reiter, Y Brooker, G Pick, CG Bennink, JR Lev, A Yewdell, JW AF Zohar, O Reiter, Y Brooker, G Pick, CG Bennink, JR Lev, A Yewdell, JW TI Convergence mechanisms of synaptogenesis between the immune and the nervous systems SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 JHU, Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. Technion Israel Inst Technol, Fac Biol, Haifa, Israel. JHU, Integrated Imaging Ctr, Dept Biol, Rockville, MD USA. Sackler Sch Med, Dept Anat & Anthropol, Ramat Aviv, Israel. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S73 EP S73 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100307 ER PT J AU Jeronimo, J Morales, O Horna, J Pariona, J Manrique, J Rubinos, J Takahashi, R AF Jeronimo, J Morales, O Horna, J Pariona, J Manrique, J Rubinos, J Takahashi, R TI Visual inspection with acetic acid for cervical cancer screening outside of low-resource settings SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE cervix neoplasms; acetic acid; diagnostic techniques and procedures; mass screening; predictive value of tests; health resources ID DEVELOPING-COUNTRIES; CYTOLOGY; EXCISION; TRIAL; CARE AB Objectives. To assess visual inspection with acetic acid (VIA) as a screening tool for use in a well-equipped health center in Peru, to evaluate VIA as an alternative or adjunct to the Papanicolaou (Pap) smear, and to determine if VIA can play a role in settings other than low-resource ones. Methods. This was a prospective study of 1921 asymptomatic women living in Lima, Peru, carried out in 1999 and 2000. The study was performed at a cancer center equipped with the latest-generation technology and highly trained oncologists. The women underwent a complete clinical evaluation, including a Pap smear and VIA. Participants with any positive test were referred for colposcopy and biopsy. Results. More women tested positive by VIA than on the Pap smear (6.9% vs. 4.2%; P = 0.0001). There were 35 women with histologic cervical intraepithelial neoplasia grade 1 (CIN 1); of these, 15 were detected by Pap and 20 by VIA (P = 0.4). A diagnosis of CIN 2 or 3 (CIN 2-3) was confirmed in a total of 13 cases; Pap detected 5 of the cases and VIA 11 of the cases (P = 0.06). The positive predictive value for detection of CIN 2+ was 8.3% for VIA and 6.3% for Pap (P = 0.5). Most importantly, while only 2.3% of patients with a positive VIA were lost to follow-up before colposcopy, that was true for 26.3% of the women with a positive Pap smear (P < 0.0001). Conclusions. VIA is useful for detection of precursor lesions of cervical cancer not only in low-resource settings but also in well-equipped health centers and cancer centers. In these non-low-resource settings, VIA has a positive predictive value comparable to the conventional Pap smear, but it is more likely to achieve earlier diagnosis, follow-up, and treatment than cytology-based screening. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Dept Hlth & Human Serv, NIH,Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Inst Enfermedades Neoplasicas Eduardo Caceres Gra, Dept Early Detect & Diagnosis, Lima, Peru. Inst Enfermedades Neoplasicas Eduardo Caceres Gra, Dept Pathol, Lima, Peru. RP Jeronimo, J (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. EM guibovij@mail.nih.gov NR 19 TC 22 Z9 24 U1 0 U2 1 PU PAN AMERICAN HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD JAN PY 2005 VL 17 IS 1 BP 1 EP 5 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 911IE UT WOS:000227995000001 PM 15720875 ER PT J AU Jin, L Weisman, M Zhang, G Ward, M Luo, J Bruckel, J Inman, R Khan, MA Schumacher, HR Maksymowych, WP Mahowald, M Martin, T Rosenbaum, JT Yu, DTY Stone, M Watson, J Dickman, E Davis, J Reveille, JD AF Jin, L Weisman, M Zhang, G Ward, M Luo, J Bruckel, J Inman, R Khan, MA Schumacher, HR Maksymowych, WP Mahowald, M Martin, T Rosenbaum, JT Yu, DTY Stone, M Watson, J Dickman, E Davis, J Reveille, JD TI Lack of association of matrix metalloproteinase 3 (MMP3) genotypes with ankylosing spondylitis susceptibility and severity SO RHEUMATOLOGY LA English DT Article DE ankylosing spondylitis; genetics; single-nucleotide polymorphisms; matrix metalloproteinase 3; disease severity ID CORONARY ATHEROSCLEROSIS; STROMELYSIN PROMOTER; DISEASE-ACTIVITY; GENETIC-SUSCEPTIBILITY; 5A/6A POLYMORPHISM; LINKAGE ANALYSIS; PROGRESSION; DISEQUILIBRIUM; LOCI; IDENTIFICATION AB Objective. To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. Methods. MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using chi(2) statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. Results. None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5' end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. Conclusion. These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity. C1 Univ Texas, Houston Hlth Sci Ctr, Houston, TX 77030 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Spondylitis Assoc Amer, Sherman Oaks, CA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Minnesota, Minneapolis, MN USA. Oregon Hlth & Sci Univ, Portland, OR USA. Univ Toronto, Toronto, ON, Canada. Univ Alberta, Edmonton, AB, Canada. RP Reveille, JD (reprint author), Univ Texas, Houston Hlth Sci Ctr, MSB 5-270,6431 Fannin, Houston, TX 77030 USA. EM john.d.reveille@uth.tmc.edu RI Jin, Li/C-1468-2009; Zhang, Ge/F-1809-2011 OI Jin, Li/0000-0002-4546-2415; FU NCRR NIH HHS [M01-RR02558]; NEI NIH HHS [EY-13139]; NIAMS NIH HHS [R01-AR46208] NR 34 TC 10 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JAN PY 2005 VL 44 IS 1 BP 55 EP 60 DI 10.1093/rheumatology/keh429 PG 6 WC Rheumatology SC Rheumatology GA 885WF UT WOS:000226187300010 PM 15546966 ER PT S AU Beare, PA Porcella, SF Seshadri, R Samuel, JE Heinzen, RA AF Beare, PA Porcella, SF Seshadri, R Samuel, JE Heinzen, RA BE Hechemy, KE Oteo, JA Raoult, DA Silverman, DJ Blanco, JR TI Preliminary assessment of genome differences between the reference nine mile isolate and two human endocarditis isolates of Coxiella burnetii SO RICKETTSIOSES: FROM GENOME TO PROTEOME, PATHOBIOLOGY, AND RICKETTSIAE AS AN INTERNATIONAL THREAT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Rickettsiae and Rickettsial Diseases CY JUN 18-21, 2005 CL Logrono, SPAIN SP Gobierno Rioja, Fund Rioja Salud, European Soc Clin Microbiol & Infect Dis, Amer Soc Rickettsiol DE endocarditis; genome; sequencing; Q fever; comparative genomics ID Q-FEVER AB This study investigates the complete genome sequences of the Nine Mile, K, and G isolates to improve our understanding of the unique virulence properties of C. burnetii and to provide important insight into the genome architecture and genetic diversity of this pathogen. C1 NIAID, Rocky Mt Lab, Genom Core Facil, NIH, Hamilton, MT 59840 USA. NIAID, Intracellular Parasites Lab, Coxiella Pathogenesis Sect, NIH, Hamilton, MT 59840 USA. Inst Genom Res, Rockville, MD 20850 USA. Texas A&M Univ, Dept Med & Microbiol Immunobiol, College Stn, TX 77843 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Lab, Genom Core Facil, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 7 TC 8 Z9 9 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-600-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1063 BP 64 EP 67 DI 10.1196/annals.1355.007 PG 4 WC Immunology; Infectious Diseases; Microbiology; Multidisciplinary Sciences SC Immunology; Infectious Diseases; Microbiology; Science & Technology - Other Topics GA BEE03 UT WOS:000236907200006 PM 16481490 ER PT S AU Howe, D Henzen, RA AF Howe, D Henzen, RA BE Hechemy, KE Oteo, JA Raoult, DA Silverman, DJ Blanco, JR TI Replication of Coxiella burnetii is inhibited in CHOK-1 cells treated with inhibitors of cholesterol metabolism SO RICKETTSIOSES: FROM GENOME TO PROTEOME, PATHOBIOLOGY, AND RICKETTSIAE AS AN INTERNATIONAL THREAT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Rickettsiae and Rickettsial Diseases CY JUN 18-21, 2005 CL Logrono, SPAIN SP Gobierno Rioja, Fund Rioja Salud, European Soc Clin Microbiol & Infect Dis, Amer Soc Rickettsiol DE parasitophorous vacuole; membrane; lipid; filipin; cholesterol; Coxiella ID LOW-DENSITY-LIPOPROTEIN; CHLAMYDIA-TRACHOMATIS; LYSOSOMES; MEMBRANE; MATURATION; TRANSPORT; VACUOLES; PROTEIN; PATHWAY AB Coxiella burnetii directs the synthesis of a large parasitophorous vacuole (PV) that is required for its replication. While some lysosomal characteristics of the PV have been described, the origin and composition of the PV membrane remain largely undefined. Cholesterol is an essential component of mammalian membranes where it lends mechanical stability and serves as a platform for signaling proteins. Using infected Chinese hamster ovary cells as a model, we examined whether cholesterol is trafficked to the C. burnetii PV membrane and the effects of inhibitors of cholesterol metabolism on C. burnetii replication. When infected cells were stained with filipin, a fluorescent polyene antifungal agent that binds cholesterol, obvious staining of PV was observed indicating the PV membrane is cholesterol-rich. Furthermore, replication of C. burnetii was significantly inhibited in cells treated with the cholesterol metabolism inhibitors lovastatin, ketoconazole, imipramine, progesterone, and U18666A. These data suggest that cholesterol is an important component of the C. burnetii PV membrane and that normal cellular cholesterol metabolism is required for optimal C. burnetii replication. C1 NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, Hamilton, MT 59840 USA. RP Henzen, RA (reprint author), NIAID, Rocky Mt Lab, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 16 TC 14 Z9 15 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-600-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1063 BP 123 EP 129 DI 10.1196/annals.1355.020 PG 7 WC Immunology; Infectious Diseases; Microbiology; Multidisciplinary Sciences SC Immunology; Infectious Diseases; Microbiology; Science & Technology - Other Topics GA BEE03 UT WOS:000236907200019 PM 16481503 ER PT S AU Shannon, JG Howe, D Heinzen, RA AF Shannon, JG Howe, D Heinzen, RA BE Hechemy, KE Oteo, JA Raoult, DA Silverman, DJ Blanco, JR TI Lack of dendritic cell maturation following infection by Coxiella burnetii synthesizing different lipopolysaccharide chemotypes SO RICKETTSIOSES: FROM GENOME TO PROTEOME, PATHOBIOLOGY, AND RICKETTSIAE AS AN INTERNATIONAL THREAT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Conference on Rickettsiae and Rickettsial Diseases CY JUN 18-21, 2005 CL Logrono, SPAIN SP Gobierno Rioja, Fund Rioja Salud, European Soc Clin Microbiol & Infect Dis, Amer Soc Rickettsiol DE Coxiella; dendritic cell; immune evasion; lipopolysaccharide ID Q-FEVER AB Coxiella burnetii is an obligate intracellular bacterium and the etiologic agent of the zoonotic disease Q fever. Symptomatic infection is normally characterized by flu-like symptoms; however, in some cases, a persistent infection can ensue that may reactivate months or years after initial exposure to cause chronic disease. The mechanisms by which this obligate parasite evades clearance by the host immune response during persistent infection are unknown. We have previously demonstrated that lipopolysaccharide (LPS) length is critical in determining the response of human dendritic cells (DC) to C. burnetii. Here, we investigated whether LPS chemotype affects DC maturation or activation. Immature human DC were infected with three virulent strains of C burnetii (Nine Mile phase 1, S, or Priscilla) that produce chemically distinct LPS molecules. None of these strains stimulated significant upregulation of cell surface markers of DC maturation. Moreover, these strains were equally deficient in inducing DC IL-12p70 production or p38 mitogen-activated protein kinase phosphorylation. Infection of DC by virulent C. burnetii without stimulating significant maturation or inflammatory cytokine production may be a mechanism of immune evasion that results in persistent infection of an otherwise immunocompetent host. Our data indicate that LPS chemotype is not a determinant of DC maturation or cytokine production in response to C. burnetii. 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, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 FU Intramural NIH HHS NR 8 TC 14 Z9 14 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-600-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1063 BP 154 EP 160 DI 10.1196/annals.1355.024 PG 7 WC Immunology; Infectious Diseases; Microbiology; Multidisciplinary Sciences SC Immunology; Infectious Diseases; Microbiology; Science & Technology - Other Topics GA BEE03 UT WOS:000236907200023 PM 16481507 ER PT S AU Chiueh, CC Andoh, T Chock, PB AF Chiueh, CC Andoh, T Chock, PB BE Wei, YH Lee, HM Hsu, CY TI Induction of thioredoxin and mitochondrial survival proteins mediates preconditioning-induced cardioprotection and neuroprotection SO ROLE OF THE MITOCHONDRIA IN HUMAN AGING AND DISEASE: FROM GENES TO CELL SIGNALING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd Scientific Meeting of the Asian-Society-for-Mitochondrial-Research-and-Medicine CY APR 01-02, 2004 CL Taipei, TAIWAN SP Asian Soc Mitochondrial Res & Med DE adaptation; ATP-sensitive potassium channel/K(ATP); Bcl-2; cyclic GMP; MnSOD; nitric oxide (NO); nitric oxide synthase (NOS); thioredoxin ID NITRIC-OXIDE SYNTHASE; INDUCED ISCHEMIC TOLERANCE; POTASSIUM CHANNEL OPENERS; MONOPHOSPHORYL-LIPID-A; RABBIT VENTRICULAR MYOCYTES; STRESS-INDUCED APOPTOSIS; BRAIN DOPAMINE NEURONS; SENSITIVE K+ CHANNEL; OXIDATIVE STRESS; S-NITROSOGLUTATHIONE AB Delayed cardio- and neuroprotection are observed following a preconditioning procedure evoked by a brief and nontoxic oxidative stress due to deprivation of oxygen, glucose, serum, trophic factors, and/or antioxidative enzymes. Preconditioning protection can be observed in vivo and is under clinical trials for preservation of cell viability following organ transplants of liver. Previous studies indicated that ischemic preconditioning increases the expression of heat-shock proteins (HSPs) and nitric oxide synthase (NOS). Our pilot studies indicate that the treatment of neuronal NOS inhibitor (7-nitroindazole) and 6Br-cGMP blocks and mimics, respectively, preconditioning protection in human neuroblastoma SH-SY5Y cells. This minireview focuses on nitric oxide-mediated cellular adaptation and the related cGMP/PKG signaling pathway in a compensatory mechanism underlying preconditioning-induced hormesis. Both preconditioning and 6Br-cGMP increase the induction of human thioredoxin (Trx) mRNA and protein for cytoprotection, which is largely prevented by transfection of cells with Trx antisense but not sense oligonucleotides. Cytosolic Trx1 and mitochondrial Trx2 suppress free radical formation, lipid peroxidation, oxidative stress, and mitochondria-dependent apoptosis; knock out/down of either Trx1 or Trx2 is detrimental to cell survival. Other recent findings; indicate that a transgenic increase of Trx in mice increases tolerance against oxidative nigral injury caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Trx1 can be translocated into nucleus and phosphoactivated CREB for a delayed induction of mitochondrial anti-apoptotic Bcl-2 and antioxidative MnSOD that is known to increase vitality and survival of cells in the brain and the heart. In conclusion, preconditioning adaptation or a brief oxidative stress induces a delayed nitric oxide-mediated compensatory mechanism for cell survival and vitality in the central nervous system and the cardiovascular system. Preconditioning-induced adaptive tolerance may be signaling through a cGMP-dependent induction of cytosolic redox protein Trx1 and subsequently mitochondrial proteins such as Bcl-2, MnSOD, and perhaps Trx2 or HSP70. C1 Taipei Med Univ, Sch Pharm, Taipei 100, Taiwan. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Dept Appl Pharmacol, Toyama 9300194, Japan. NHLBI, Biochem Lab, Dept Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Chiueh, CC (reprint author), Taipei Med Univ, Sch Pharm, 250 Wu Hsing St, Taipei 100, Taiwan. EM chiueh@tmu.edu.tw FU Intramural NIH HHS NR 122 TC 47 Z9 51 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-541-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1042 BP 403 EP 418 DI 10.1196/annals.1338.034 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BCR22 UT WOS:000230893400048 PM 15965087 ER PT S AU Sviridov, AP Chernomordik, V Hassan, M Gandjbakhche, A AF Sviridov, AP Chernomordik, V Hassan, M Gandjbakhche, A BE Zimnyakov, DA TI Potentials of skin diagnostic with digital photometric patterning of backscattered linearly polarized light SO Saratov Fall Meeting 2004: Coherent Optics of Ordered and Random Media V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 2004 Saratov Fall Meeting CY SEP 21-24, 2004 CL Saratov, RUSSIA SP Russian Fdn Basic Res, US Civilian Res & Dev Fdn Independent States Former Soviet Union, SPIE Russian Chapter, IEEE MTT, ED, AP, CPMT Saratov Penza Chapter, TECHNOSERV S, Ltd, Almus, Ltd, Saratov State Univ, Res Educ Inst Opt & Biophoton SSU, Russian Acad Sci, Inst Precis Mech & Control, Res Educ Ctr Nonlinear Dynam & Biophys CRDF & Minist Educ & Sci RF, Volga Reg Ctr New Informat Technologies, Russian Acad Nat Sci, Saratov Reg Div, Russian Soc Photobiol, Saratov State Tech Univ, Inst Business & Business Adm DE polarized videoreflectometry; light propagation in tissue; equi-intensity profiles of light; collagen fiber orientation; optical diagnosis; fibrosis ID OPTICAL-PROPERTIES; SCATTERING; ANISOTROPY; TISSUE; PROPAGATION; RODS AB Potentials of two modalities of skin diagnostic with focused and expanded linearly polarized probe light are studied. For the focused beam (wavelength 650 nm) the photometric patterns of light backscattered from skin and collagenous tissue phantoms were recorded using digital camera. It is shown that equiintensity contours are well fitted with ellipses that appeared to follow the orientation of collagen fibers. In the peripheral zone from the entry point of the probe beam the ratio of the ellipses semi-axes is correlated with the ratio of reduced scattering coefficients obtained from intensity profiles. In the vicinity of the entry point it depends on the mutual orientation of polarization vector and collagen fibers. For the expanded probe beam the digital mapping of the residual polarization degree of backscattered linearly polarized light allowed visualization of the hidden structure of earlier fibrosis of the mouse skin arisen from X-ray treatment. The structure of the skin fibrosis was enhanced using Fourier transform filtering of polarization degree pattern. The pattern scanning with Pearson correlation coefficient was developed to determine the orientation and characteristic size of hidden structure. Both modalities may be potentially used for diagnostic of skin abnormalities, such as fibrosis. C1 NIH, Bethesda, MD 20892 USA. RP Sviridov, AP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5753-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5772 BP 105 EP 113 DI 10.1117/12.636860 PG 9 WC Optics SC Optics GA BCW70 UT WOS:000231583900012 ER PT J AU Pastides, H Doll, R Acquavella, JF Alavanja, M AF Pastides, H Doll, R Acquavella, JF Alavanja, M TI Agricultural exposures and cancer - Preface SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Editorial Material C1 Univ S Carolina, Norman J Arnold Sch Publ Hlth, Columbia, SC 29208 USA. Univ Oxford, Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX1 2JD, England. Univ Oxford, Radcliffe Infirm, Epidemiol Studies Unit, Oxford OX1 2JD, England. Monsanto Co, Regulatory Affairs, St Louis, MO USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Pastides, H (reprint author), Univ S Carolina, Norman J Arnold Sch Publ Hlth, Columbia, SC 29208 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 2005 VL 31 SU 1 BP 3 EP 4 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 966HI UT WOS:000232010300001 ER PT J AU Alavanja, MCR Sandler, DP Lynch, CF Knott, C Lubin, JH Tarone, R Thomas, K Dosemeci, M Barker, J Hoppin, JA Blair, A AF Alavanja, MCR Sandler, DP Lynch, CF Knott, C Lubin, JH Tarone, R Thomas, K Dosemeci, M Barker, J Hoppin, JA Blair, A TI Cancer incidence in the agricultural health study SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article; Proceedings Paper CT International Symposium on Agricultural Exposures and Cancer CY NOV 19-22, 2002 CL Oxford Univ Green Coll, Oxford, ENGLAND SP CropLife Int, CropLife Amer, European Crop Protect Assoc, Int Agcy Res Canc HO Oxford Univ Green Coll DE agricultural exposure; cancer etiology; commercial applicator; farmer; melanoma; ovarian cancer; prostate cancer; spouse of farmer; standard incidence ratio ID NON-HODGKINS-LYMPHOMA; PROSTATE-CANCER; MULTIPLE-MYELOMA; PESTICIDE EXPOSURES; RISK-FACTORS; FARMERS; MORTALITY; DEATH; IOWA; MEN AB Objectives This large, prospective cohort study of private applicators, commercial applicators, and spouses of fanner applicators was undertaken to ascertain the etiology of cancers elevated in agriculture. Methods The participants were matched to cancer registry files in Iowa and North Carolina. Incident cases were identified from enrollment through 31 December 2002. Standardized incidence ratios (SIR) were used to compare the cancer incidence of the participants with that of the total population in the two states. Result The overall cancer incidence among farmers [SIR 0.88, 95% confidence interval (95% CI) 0.84-0.91] and their spouses (SIR 0.84, 95% CI 0.80-0.90) were significantly lower than expected, particularly for respiratory and urinary cancers. Commercial pesticide applicators had an overall cancer incidence comparable with the expected (SIR 1.01, 95% CI 0.84-1.20). Smoking prevalence was significantly lower than the national average. Prostate cancer was elevated among private applicators (SIR 1.24, 95% Cl 1.18-1.33) and commercial applicators (SIR 1.37, 0.98-1.86). Excess ovarian cancer was observed for female applicators (SIR 2.97, 95% Cl 1.28-5.85), but not for female spouses (SIR 0.55, 95% CI 0.38-0.78). Female spouses had a significant excess of melanoma (SIR 1.64, 95% Cl 1.24-2.09), which was not observed among pesticide applicators. Conclusions Low overall cancer incidence rates seem to be a result of low overall smoking prevalence and other lifestyle factors, while excess cancer of the prostate and ovaries among applicators may be occupationally related. The excess risk of melanoma observed among spouses was unexpected. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. Battelle Mem Inst, Durham, NC USA. US EPA, Res Triangle Pk, NC 27711 USA. IMS, Silver Spring, MD USA. RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8000, Bethesda, MD 20892 USA. EM alavanjm@mail.nih.gov NR 33 TC 61 Z9 69 U1 3 U2 6 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 2005 VL 31 SU 1 BP 39 EP 45 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 966HI UT WOS:000232010300007 PM 16190148 ER EF