FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Yan, JZ Xu, LS Crawford, G Wang, ZF Burgess, SM AF Yan, JZ Xu, LS Crawford, G Wang, ZF Burgess, SM TI The forkhead transcription factor FoxI1 remains bound to condensed mitotic chromosomes and stably remodels chromatin structure SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INDUCED GENE ACTIVATION; DNA-BINDING; CELL-CYCLE; MAMMALIAN-CELLS; REPETITIVE DNA; NUCLEAR-MATRIX; HISTONE H1; ZEBRAFISH; EXPRESSION; PROTEIN AB similar to the winged-helix structures of histones H1 and H5. Little is known about Fox protein binding in the of higher-order chromatin structure in living cells. We created a stable cell line expressing FoxI1-green fluorescent protein (GFP) or FoxI1-V5 fusion proteins under control of the reverse tetracycline-controlled transactivator doxycycline inducible system and found that unlike most transcription factors, FoxI1 remains bound to the condensed chromosomes during mitosis. To isolate DNA fragments directly bound by the FoxI1 protein within living cells, we performed chromatin immunoprecipitation assays (ChIPs) with antibodies to either enhanced GFP or the V5 epitope and subcloned the FoxI1-enriched DNA fragments. Sequence analyses indicated that 88% (106/121) of CUP sequences contain the consensus binding sites for all Fox proteins. Testing CUP sequences with a quantitative DNase I hypersensitivity assay showed that FoxI1 created stable DNase I sensitivity changes in condensed chromosomes. The majority of ChIP targets and random targets increased in resistance to DNase I in FoxI1-expressing cells, but a small number of targets became more accessible to DNase I. Consistently, the accessibility of micrococcal nuclease to chromatin was generally inhibited. Micrococcal nuclease partial digestion generated a ladder in which all oligonucleosomes were slightly longer than those observed with the controls. On the basis of these findings, we propose that FoxI1 is capable of remodeling chromatin higher-order structure and can stably create site-specific changes in chromatin to either stably create or remove DNase I hypersensitive sites. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Burgess, SM (reprint author), NHGRI, Genome Technol Branch, NIH, Bldg 50,Rm 5537,50 South Dr, Bethesda, MD 20892 USA. EM burgess@mail.nih.gov OI Burgess, Shawn/0000-0003-1147-0596 FU Intramural NIH HHS NR 75 TC 51 Z9 52 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 2006 VL 26 IS 1 BP 155 EP 168 DI 10.1128/MCB.26.1.155-168.2006 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 009OK UT WOS:000235121400012 PM 16354687 ER PT J AU Sobeck, A Stone, S Costanzo, V de Graaf, B Reuter, T de Winter, J Wallisch, M Akkari, Y Olson, S Wang, WD Joenje, H Christian, JL Lupardus, PJ Cimprich, KA Gautier, J Hoatlin, ME AF Sobeck, A Stone, S Costanzo, V de Graaf, B Reuter, T de Winter, J Wallisch, M Akkari, Y Olson, S Wang, WD Joenje, H Christian, JL Lupardus, PJ Cimprich, KA Gautier, J Hoatlin, ME TI Fanconi anemia proteins are required to prevent accumulation of replication-associated DNA double-strand breaks SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID ATR-DEPENDENT CHECKPOINT; INTERSTRAND CROSS-LINKS; WERNER-SYNDROME PROTEIN; SYNDROME GENE-PRODUCTS; XENOPUS EGG EXTRACTS; S-PHASE CHECKPOINT; HOMOLOGOUS RECOMBINATION; CELL-CYCLE; NUCLEAR-COMPLEX; DAMAGE RESPONSE AB Fanconi anemia (FA) is a multigene cancer susceptibility disorder characterized by cellular hypersensitivity to DNA interstrand cross-linking agents such as mitomycin C (MMC). FA proteins are suspected to function at the interface between cell cycle checkpoints, DNA repair, and DNA replication. Using replicating extracts from Xenopus eggs, we developed cell-free assays for FA proteins (xFA). Recruitment of the xFA core complex and xFANCD2 to chromatin is strictly dependent on replication initiation, even in the presence of MMC indicating specific recruitment to DNA lesions encountered by the replication machinery. The increase in xFA chromatin binding following treatment with MMC is part of a caffeine-sensitive S-phase checkpoint that is controlled by xATR. Recruitment of xFANCD2, but not xFANCA, is dependent on the xATR-xATR-interacting protein (xATRIP) complex. Immunodepletion of either xFANCA or xFANCD2 from egg extracts results in accumulation of chromosomal DNA breaks during replicative synthesis. Our results suggest coordinated chromatin recruitment of xFA proteins in response to replication-associated DNA lesions and indicate that xFA proteins function to prevent the accumulation of DNA breaks that arise during unperturbed replication. C1 Oregon Hlth Sci Univ, Div Biochem & Mol Biol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. Columbia Univ, Dept Genet & Dev, Coll Phys & Surg, New York, NY 10032 USA. Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands. NIA, TRIAD Ctr, NIH, Baltimore, MD 21224 USA. Canc Res UK London Res Inst, Gen Stabil Unit, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. Stanford Univ, Dept Mol Pharmacol, Stanford, CA 94305 USA. RP Hoatlin, ME (reprint author), Oregon Hlth Sci Univ, Div Biochem & Mol Biol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM hoatlinm@ohsu.edu RI Gautier, jean/A-2774-2008 FU NCI NIH HHS [R01 CA092245, CA112775, R01 CA112775, CA092245]; NICHD NIH HHS [R03 HD050242]; NIGMS NIH HHS [GM62193, R01 GM062193] NR 103 TC 66 Z9 66 U1 1 U2 3 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 2006 VL 26 IS 2 BP 425 EP 437 DI 10.1128/MCB.26.2.425-437.2006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 003IV UT WOS:000234676100004 PM 16382135 ER PT J AU Dhillon, N Oki, M Szyjka, SJ Aparicio, OM Kamakaka, RT AF Dhillon, N Oki, M Szyjka, SJ Aparicio, OM Kamakaka, RT TI H2A.Z functions to regulate progression through the cell cycle SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN REMODELING COMPLEX; CEREVISIAE CHROMOSOME VI; DNA-POLYMERASE-EPSILON; SACCHAROMYCES-CEREVISIAE; S-PHASE; REPLICATION ORIGINS; HISTONE VARIANT; MULTIPROTEIN COMPLEX; ORDERED RECRUITMENT; GENOMIC INSTABILITY AB Histone H2A variants are highly conserved proteins found ubiquitously in nature and thought to perform specialized functions in the cell. Studies in yeast on the histone H2A variant H2A.Z have shown a role for this protein in transcription as well as chromosome segregation. Our studies have focused on understanding the role of H2A.Z during cell cycle progression. We found that htz1 Delta cells were delayed in DNA replication and progression through the cell cycle. Furthermore, cells lacking H2A.Z required the S-phase checkpoint pathway for survival. We also found that H2A.Z localized to the promoters of cyclin genes, and cells lacking H2A.Z were delayed in the induction of these cyclin genes. Several different models are proposed to explain these observations. C1 NICHD, NIH, Unit Chromat & Transcript, Bethesda, MD 20892 USA. Univ So Calif, Mol & Computat Biol Program, Los Angeles, CA 90089 USA. RP NICHD, NIH, Unit Chromat & Transcript, Bldg 18T,Rm 106,18 Library D, Bethesda, MD 20892 USA. EM Rohinton@helix.nih.gov FU NIGMS NIH HHS [R01 GM065494] NR 95 TC 50 Z9 55 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2006 VL 26 IS 2 BP 489 EP 501 DI 10.1128/MCB.26.2.489-501.2006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 003IV UT WOS:000234676100010 PM 16382141 ER PT J AU Furusawa, T Lim, JH Catez, F Birger, Y Mackem, S Bustin, M AF Furusawa, T Lim, JH Catez, F Birger, Y Mackem, S Bustin, M TI Down-regulation of nucleosomal binding protein HMGN1 expression during embryogenesis modulates Sox9 expression in chondrocytes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROUP CHROMOSOMAL-PROTEINS; MOBILITY GROUP PROTEIN-14; CAMPOMELIC DYSPLASIA; HISTONE H1; CHROMATIN; DIFFERENTIATION; MOUSE; PHOSPHORYLATION; GROWTH; HMG-17 AB We find that during embryogenesis the expression of HMGN1, a nuclear protein that binds to nucleosomes and reduces the compaction of the chromatin fiber, is progressively down-regulated throughout the entire embryo, except in committed but continuously renewing cell types, such as the basal layer of the epithelium. In the developing limb bud, the expression of HMGN1 is complementary to Sox9, a master regulator of the chondrocyte lineage. In limb bud micromass cultures, which faithfully mimic in vivo chondrogenic differentiation, loss of HMGN1 accelerates differentiation. Expression of wild-type HMGN1, but not of a mutant HMGN1 that does not bind to chromatin, in Hmgn1(-/-) micromass cultures inhibits Sox9 expression and retards differentiation. Chromatin immunoprecipitation analysis reveals that HMGN1 binds to Sox9 chromatin in cells that are poised to express Sox9. Loss of HMGN1 elevates the amount of HMGN2 bound to Sox9, suggesting functional redundancy among these proteins. These findings suggest a role for HMGN1 in chromatin remodeling during embryogenesis and in the activation of Sox9 during chondrogenesis. C1 NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Andong Natl Univ, Dept Biol, Andong 760749, Gyungsangbuk, South Korea. RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, NIH, Bldg 37,Room 3122,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU Intramural NIH HHS [Z01 BC004496-30] NR 36 TC 40 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2006 VL 26 IS 2 BP 592 EP 604 DI 10.1128/MCB.26.2.592-604.2006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 003IV UT WOS:000234676100019 PM 16382150 ER PT J AU Kohn, KW Aladjem, MI Weinstein, JN Pommier, Y AF Kohn, KW Aladjem, MI Weinstein, JN Pommier, Y TI Molecular interaction maps of bioregulatory networks: A general rubric for systems biology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-CYCLE; COMPLEX NETWORKS; INFORMATION; SIMULATION; SWITCH; YEAST AB A standard for bioregulatory network diagrams is urgently needed in the same way that circuit diagrams are needed in electronics. Several graphical notations have been proposed, but none has become standard. We have prepared many detailed bioregulatory network diagrams using the molecular interaction map (MIM) notation, and we now feel confident that it is suitable as a standard. Here, we describe the MIM notation formally and discuss its merits relative to alternative proposals. We show by simple examples how to denote all of the molecular interactions commonly found in bioregulatory networks. There are two forms of MIM diagrams. "Heuristic" MIMs present the repertoire of interactions possible for molecules that are colocalized in time and place. "Explicit" MIMs define particular models (derived from heuristic MIMs) for computer simulation. We show also how pathways or processes can be highlighted on a canonical heuristic MIM. Drawing a MIM diagram, adhering to the rules of notation, imposes a logical discipline that sharpens one's understanding of the structure and function of a network. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kohnk@dc37a.nci.nih.gov RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU Intramural NIH HHS NR 26 TC 75 Z9 78 U1 0 U2 4 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 2006 VL 17 IS 1 BP 1 EP 13 DI 10.1091/mbc.E05-09-0824 PG 13 WC Cell Biology SC Cell Biology GA 999ON UT WOS:000234399300001 PM 16267266 ER PT J AU Kamijo, K Ohara, N Abe, M Uchimura, T Hosoya, H Lee, JS Miki, T AF Kamijo, K Ohara, N Abe, M Uchimura, T Hosoya, H Lee, JS Miki, T TI Dissecting the role of Rho-mediated signaling in contractile ring Formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID REGULATORY LIGHT-CHAIN; CULTURED EPITHELIAL-CELLS; PHOSPHORYLATED MYOSIN-II; KINESIN-LIKE PROTEIN; GTP-BINDING PROTEIN; DIFFERENTIAL LOCALIZATION; MAMMALIAN-CELLS; EXCHANGE FACTOR; CITRON KINASE; CYTOKINESIS AB In anaphase, microtubules provide a specification signal for positioning of the contractile ring. However, the nature of the signal remains unknown. The small GTPase Rho is a potent regulator of cytokinesis, but the involvement of Rho in contractile ring formation is disputed. Here, we show that Rho serves as a microtubule-dependent signal that specifies the position of the contractile ring. We found that Rho translocates to the equatorial region before furrow ingression. The Rho-specific inhibitor C3 exoenzyme and small interfering RNA to the Rho GDP/GTP exchange factor ECT2 prevent this translocation and disrupt contractile ring formation, indicating that active Rho is required for contractile ring formation. ECT2 forms a complex with the GTPase-activating protein MgcRacGAP and the kinesinlike protein MKLP1 at the central spindle, and the localization of ECT2 at the central spindle depends on MgcRacGAP and MKLP1. In addition, we show that the bundled microtubules direct Rho-mediated signaling molecules to the furrowing site and regulate furrow formation. Our study provides strong evidence for the requirement of Rho-mediated signaling in contractile ring formation. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Hiroshima Univ, Grad Sch Sci, Dept Biol Sci, Higashihiroshima 7398526, Japan. RP Kamijo, K (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM kkamijo@ja3.so-net.ne.jp FU Intramural NIH HHS NR 44 TC 124 Z9 131 U1 1 U2 6 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 2006 VL 17 IS 1 BP 43 EP 55 PG 13 WC Cell Biology SC Cell Biology GA 999ON UT WOS:000234399300005 PM 16236794 ER PT J AU Jovanovic, OA Brown, FD Donaldson, JG AF Jovanovic, OA Brown, FD Donaldson, JG TI An effector domain mutant of Arf6 implicates phospholipase D in endosomal membrane recycling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ADP-RIBOSYLATION FACTOR; PLASMA-MEMBRANE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; REGULATED EXOCYTOSIS; DOWNSTREAM EFFECTOR; ACTIN CYTOSKELETON; PROTEIN; CELLS; STIMULATION; RECRUITMENT AB In this study, we investigated the role of phospholipase D (PLD) in mediating Arf6 function in cells. Expression of Arf6 mutants that are defective in activating PLD, Arf6N48R and Arf6N481, inhibited membrane recycling to the plasma membrane (PM), resulting in an accumulation of tubular endosomal membranes. Additionally, unlike wild-type Arf6, neither Arf6 mutant could generate protrusions or recruit the Arf6 GTPase activating protein (GAP) ACAP1 onto the endosome in the presence of aluminum fluoride. Remarkably, all of these phenotypes, including accumulated tubular endosomes, blocked recycling, and failure to make protrusions and recruit ACAP effectively, could be recreated in either untransfected cells or cells expressing wild-type Arf6 by treatment with 1-butanol to inhibit the formation of phosphatidic acid (PA), the product of PLD. Moreover, most of the defects present in cells expressing Arf6N48R or N481 could be reversed by treatment with agents expected to elevate PA levels in cells. Together, these observations provide compelling evidence that Arf6 stimulation of PLD is required for endosomal membrane recycling and GAP recruitment. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov FU NHLBI NIH HHS [Z01 HL000517-10] NR 47 TC 51 Z9 53 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2006 VL 17 IS 1 BP 327 EP 335 DI 10.1091/mbc.E05-06-0523 PG 9 WC Cell Biology SC Cell Biology GA 999ON UT WOS:000234399300030 PM 16280360 ER PT J AU Comer, FI Parent, CA AF Comer, FI Parent, CA TI Phosphoinositide 3-kinase activity controls the chemoattractant-mediated activation and adaptation of adenylyl cyclase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; DIRECTIONAL CELL-MOVEMENT; CAMP SIGNALING RESPONSE; CYCLIC 3',5'-AMP RELAY; DICTYOSTELIUM-DISCOIDEUM; LEADING-EDGE; POLYMORPHONUCLEAR LEUKOCYTES; CHEMOTACTIC RESPONSIVENESS; EUKARYOTIC CHEMOTAXIS; NEUTROPHIL CHEMOTAXIS AB The binding of chemoattractants to cognate G protein-coupled receptors activates a variety of signaling cascades that provide spatial and temporal cues required for chemotaxis. When subjected to uniform stimulation, these responses are transient, showing an initial peak of activation followed by a period of adaptation, in which activity subsides even in the presence of stimulus. A tightly regulated balance between receptor-mediated stimulatory and inhibitory pathways controls the kinetics of activation and subsequent adaptation. In Dictyostelium, the adenylyl cyclase expressed during aggregation (ACA), which synthesizes the chemoattractant cAMP, is essential to relay the signal to neighboring cells. Here, we report that cells lacking phosphoinositide 3-kinase (PI3K) activity are deficient in signal relay. In LY294002-treated cells, this defect is because of a loss of ACA activation. In contrast, in cells lacking PI3K1 and PI3K2, the signal relay defect is because of a loss of ACA adaptation. We propose that the residual low level of 3-phosphoinositides in pi3k(1-/2-) cells is sufficient to generate the initial peak of ACA activity, yet is insufficient to sustain the inhibitory phase required for its adaptation. Thus, PI3K activity is poised to regulate both ACA activation and adaptation, thereby providing a link to ensure the proper balance of counteracting signals required to maintain optimal chemoresponsiveness. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIGMS, Pharmacol Res Associate Training Fellowship Progr, NIH, Bethesda, MD 20892 USA. RP NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM parentc@helix.nih.gov FU Intramural NIH HHS NR 61 TC 27 Z9 28 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2006 VL 17 IS 1 BP 357 EP 366 DI 10.1091/mbc.E05-08-0781 PG 10 WC Cell Biology SC Cell Biology GA 999ON UT WOS:000234399300033 PM 16267269 ER PT J AU Chakraborty, P Wei, J van Deursen, J Levay, A Boehmer, T Malureanu, L Dasso, M Forbes, D Seemann, J Fontoura, B AF Chakraborty, P. Wei, J. van Deursen, J. Levay, A. Boehmer, T. Malureanu, L. Dasso, M. Forbes, D. Seemann, J. Fontoura, B. TI Nucleoporins Are Targets of the APC and Regulate Cell Cycle Progression SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Chakraborty, P.; Wei, J.; Seemann, J.; Fontoura, B.] Univ Texas SW, Dallas, TX USA. [van Deursen, J.; Malureanu, L.] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA. [Levay, A.] Univ Miami, Miller Sch Med, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. [Boehmer, T.] MIT, Dept Biol, Cambridge, MA USA. [Dasso, M.] NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD USA. [Forbes, D.] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700468 ER PT J AU Chen, Z Noben-Trauth, K AF Chen, Z. Noben-Trauth, K. TI Characterization of a Novel Gene, Jxc1, Which Is Associated with the Development of Hearing in Mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Chen, Z.; Noben-Trauth, K.] NIDCD, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700543 ER PT J AU Cho, H Kehrl, J AF Cho, H. Kehrl, J. TI Interaction between Heterotrimeric Gialpha Proteins and Their Regulator, RGS14 in the Mammalian Centrosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Cho, H.; Kehrl, J.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700152 ER PT J AU Dasgupta, A Jeong, S Jang, K Brady, JN AF Dasgupta, A. Jeong, S. Jang, K. Brady, J. N. TI Adenosine 2,3-dialdehyde (AdOx) Causes Reactivation of p53 and Induction of the G2/M Checkpoint Resulting in Programmed Cell Death in HTLV-1 Transformed Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Dasgupta, A.] NCI, Cellular Oncol Lab, NIH, Virus Tumor Biol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700576 ER PT J AU de Wever, O Gheldhof, A van Valckenborgh, D Hendrix, A Narine, K Westbroek, W Denys, H Gespach, C Bracke, M AF de Wever, O. Gheldhof, A. van Valckenborgh, D. Hendrix, A. Narine, K. Westbroek, W. Denys, H. Gespach, C. Bracke, M. TI Growth Factor Modulation Under Three Dimensional Conditions of Fibroblast Proliferation, Differentiation, and Invasion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [de Wever, O.; Gheldhof, A.; van Valckenborgh, D.; Hendrix, A.; Bracke, M.] Ghent Univ Hosp, Expt Cancerol Lab, B-9000 Ghent, Belgium. [Narine, K.] Ghent Univ Hosp, Lab Expt Cardiol, B-9000 Ghent, Belgium. [Westbroek, W.] NIH, Med Genet Branch, Bethesda, MD 20892 USA. [Gespach, C.] INSERM, U673, Paris, France. RI de wever, olivier/J-3094-2013 OI de wever, olivier/0000-0002-5453-760X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 SU S PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700362 ER PT J AU Gavard, J Gutkind, J AF Gavard, J. Gutkind, J. TI VEGF Controls Endothelial Cell Permeability by Promoting the Rac-dependent Endocytosis of VE-cadherin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Gavard, J.; Gutkind, J.] NIDCR, OPCB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700051 ER PT J AU Hendrix, A Westbroek, W Denys, H Van Valckenborgh, D Bracke, M Cocquyt, V Gahl, W Van Belle, S De Wever, O AF Hendrix, A. Westbroek, W. Denys, H. Van Valckenborgh, D. Bracke, M. Cocquyt, V. Gahl, W. Van Belle, S. De Wever, O. TI New Insights in the Link between Rab27b GTPase and Breast Cancer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Hendrix, A.; Denys, H.; Van Valckenborgh, D.; Bracke, M.; Cocquyt, V.; Van Belle, S.; De Wever, O.] Univ Ghent, B-9000 Ghent, Belgium. [Westbroek, W.; Gahl, W.] NIH, NHGRI, Bethesda, MD 20892 USA. RI de wever, olivier/J-3094-2013 OI de wever, olivier/0000-0002-5453-760X NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2006 VL 17 PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700363 ER PT J AU Huang, N Shi, C Hwang, I Kehrl, JH AF Huang, N. Shi, C. Hwang, I. Kehrl, J. H. TI Coordinate Regulation of Gi alpha, RGS1, and CXCR4 in B Lymphocyte Chemotaxis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Huang, N.; Shi, C.; Hwang, I.; Kehrl, J. H.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700029 ER PT J AU Karacsonyi, CV Miguel, AS Puertollano, R AF Karacsonyi, C. V. Miguel, A. San Puertollano, R. TI Mucolipin-2 Localizes to the Arf6-associated Pathway and Regulates Trafficking of GPI-proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Karacsonyi, C. V.; Miguel, A. San; Puertollano, R.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700400 ER PT J AU Laabs, T McCann, T Katagiri, Y Fawcett, J Geller, H AF Laabs, T. McCann, T. Katagiri, Y. Fawcett, J. Geller, H. TI Reducing Chondroitin Sulfate Synthesis Decreases the Inhibitory Activity of Astrocyte-derived Chondroitin Sulfate Proteoglycans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Laabs, T.; McCann, T.; Katagiri, Y.; Geller, H.] NHLBI, NIH, Bethesda, MD 20892 USA. [Fawcett, J.] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700365 ER PT J AU Lao, Q Kobrinsky, E Harry, J Soldatov, NM AF Lao, Q. Kobrinsky, E. Harry, J. Soldatov, N. M. TI Multiple Determinants of the beta(2)-subunit Facilitation of the Ca(v)1.2 Calcium Channel Voltage Gating: Characterization of the C-terminal beta(2) Determinant SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lao, Q.; Kobrinsky, E.; Harry, J.; Soldatov, N. M.] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700523 ER PT J AU Ma, H Blake, T Liu, P Balla, T AF Ma, H. Blake, T. Liu, P. Balla, T. TI Type III Phosphatidylinositol 4-kinase alpha Is Required for Pectoral Fin Development in Zebrafish SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ma, H.; Balla, T.] NICHD, ERRB SMST, NIH, Bethesda, MD USA. [Blake, T.; Liu, P.] NHGRI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700235 ER PT J AU O'Quinn, RP Salmon, WC Moree, B Salmon, ED AF O'Quinn, R. P. Salmon, W. C. Moree, B. Salmon, E. D. TI Long-term FLIP Experiments Reveal Two Compartments of Mad1 at Mitotic Kinetochores SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [O'Quinn, R. P.; Moree, B.; Salmon, E. D.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. [O'Quinn, R. P.] NIH UNC Grad Partnerships Program Cell Motil & Cy, Bethesda, MD USA. [Salmon, W. C.] Univ N Carolina, Michael Hooker Microscopy Facil, Chapel Hill, NC USA. [Salmon, E. D.] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700325 ER PT J AU Rafikova, E Melikov, K Ramos, C Chernomordik, L AF Rafikova, E. Melikov, K. Ramos, C. Chernomordik, L. TI Fusion between Nuclear Membrane Vesicles and Protein-free Liposomes Results in Nuclear Assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Rafikova, E.; Melikov, K.; Chernomordik, L.] NIH, Bethesda, MD 20892 USA. [Ramos, C.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700409 ER PT J AU Sankala, HM Hait, N Paugh, S Milstien, S Spiegel, S AF Sankala, H. M. Hait, N. Paugh, S. Milstien, S. Spiegel, S. TI p53 Independent Regulation of p21 Expression by Sphingosine Kinase 2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sankala, H. M.; Hait, N.; Paugh, S.; Spiegel, S.] Virginia Commonwealth Univ, Richmond, VA USA. [Milstien, S.] NIH, Bethesda, MD 20892 USA. RI Paugh, Steven/A-7739-2008 OI Paugh, Steven/0000-0001-5697-9228 NR 0 TC 0 Z9 0 U1 0 U2 2 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 PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700156 ER PT J AU Schulz, TA Prinz, WA AF Schulz, T. A. Prinz, W. A. TI Subcellular Localization of Yeast Oxysterol Binding Protein Homologs SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Schulz, T. A.; Prinz, W. A.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700382 ER PT J AU Sperber, SM Dawid, IB AF Sperber, S. M. Dawid, I. B. TI Role and Regulation of Barx1 in the Zebrafish Pharyngeal Arches SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sperber, S. M.; Dawid, I. B.] NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700412 ER PT J AU Teng, R Gavrilova, O Suzuki, N Yamamoto, M Noguchi, C AF Teng, R. Gavrilova, O. Suzuki, N. Yamamoto, M. Noguchi, C. TI Lack of Erythropoietin Receptor in Non-hematopoietic Tissues Results in Insulin Resistance SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Teng, R.; Noguchi, C.] NIH, Mol Med Branch, Bethesda, MD 20892 USA. [Gavrilova, O.] NIH, Mouse Metab Core Lab, Bethesda, MD 20892 USA. [Suzuki, N.; Yamamoto, M.] Univ Tsukuba, Ctr TARA & ERATO JST, Tsukuba, Ibaraki, Japan. RI Suzuki, Norio/F-3456-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700268 ER PT J AU Toth, B Balla, A Ma, H Knight, ZA Shokat, KM Balla, T AF Toth, B. Balla, A. Ma, H. Knight, Z. A. Shokat, K. M. Balla, T. TI Phosphatidylinositol 4-kinase III beta Regulates the Transport of Ceramide between the Endoplasmic Reticulum and Golgi SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Toth, B.; Balla, A.; Ma, H.; Balla, T.] NICHD, ERRB SMST, NIH, Bethesda, MD USA. [Knight, Z. A.] Univ Calif San Francisco, Program Chem & Chem Biol, San Francisco, CA 94143 USA. [Shokat, K. M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. [Shokat, K. M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 SU S PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700528 ER PT J AU Volkening, K Ge, W Leystra-Lantz, C Jaffe, H Strong, MJ AF Volkening, K. Ge, W. Leystra-Lantz, C. Jaffe, H. Strong, M. J. TI Identification of a Hexanucleotide Repeat in the 3 ' UTR of Human Low Molecular Weight Neurofilament (NFL) That Affects mRNA Structure, Stability, and Interaction with 14-3-3 Proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Volkening, K.; Ge, W.; Leystra-Lantz, C.; Strong, M. J.] Robarts Res Inst, London, ON N6A 5C1, Canada. [Jaffe, H.] NINDS, Prot Peptide Sequencing Facil, Natl Inst Hlth, Bethesda, MD 20892 USA. [Strong, M. J.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada. RI Strong, Michael/H-9689-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 SU S PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700225 ER PT J AU Voss, C Prinz, W AF Voss, C. Prinz, W. TI What Keeps Reticulons in the Peripheral ER? SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Voss, C.; Prinz, W.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 PY 2006 VL 17 PG 1 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700419 ER PT J AU Zheng, Y Li, B Kanungo, J Kesavapany, S Amin, N Grant, P Pant, HC AF Zheng, Y. Li, B. Kanungo, J. Kesavapany, S. Amin, N. Grant, P. Pant, H. C. TI Inhibition of Cdk5 Sustains Mapk (Erk1/2) Activation in Cortical Neurons and Induces Apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Zheng, Y.; Li, B.; Kanungo, J.; Kesavapany, S.; Amin, N.; Grant, P.; Pant, H. C.] NINDS, LNC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2006 VL 17 PG 2 WC Cell Biology SC Cell Biology GA V05MS UT WOS:000207130700096 ER PT J AU Lee, TL Yeh, J Van Waes, C Chen, Z AF Lee, TL Yeh, J Van Waes, C Chen, Z TI Epigenetic modification of SOCS-1 differentially regulates STAT3 activation in response to interleukin-6 receptor and epidermal growth factor receptor signaling through JAK and/or MEK in head and neck squamous cell carcinomas SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CONSTITUTIVE ACTIVATION; PROMOTER HYPERMETHYLATION; IN-VIVO; HEPATOCELLULAR-CARCINOMA; SERINE PHOSPHORYLATION; NEGATIVE REGULATOR; JAK/STAT PATHWAY; CANCER-PATIENTS; FACTOR-ALPHA; CYTOKINE AB Signal transducer and activator of transcription 3 (STAT3) has been reported to be activated by interleukin-6 receptor (IL-6R) or epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), which may have important implications for responsiveness to therapeutics targeted at EGFR, IL-6R, or intermediary kinases. Suppressor of cytokine signaling-1 (SOCS-1) has been implicated recently in the negative regulation of IL-6R/Janus-activated kinase (JAK)-mediated activation of STAT3, suggesting that SOCS-1 could affect alternative activation of STAT3 by EGFR, IL-6R, and associated kinases. We investigated whether epigenetic modification of SOCS-1 affects STAT3 activation in response to IL-6R-, EGFR-, JAK-, or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-mediated signal activation. STAT3 was predominantly activated by IL-6R via Jak1/Jak2 in HNSCC lines UMSCC-9 and UMSCC-38 in association with transcriptional silencing of SOCS-1 by hypermethylation. In UMSCC-11A cells with unmethylated SOCS-1, STAT3 activation was regulated by both EGFR and IL-6R via a JAK-independent pathway involving MEK. Pharmacologic inhibitors of JAK and MEK and expression of SOCS-1 following demethylation or transient transfection inhibited STAT3 activation and cell proliferation and induced cell apoptosis in corresponding cell lines. Hypermethylation of SOCS-1 was found in about one-third of human HNSCC tissues, making it a potentially relevant marker for STAT-targeted therapy in HNSCC patients. We conclude that SOCS-1 methylation status can differentially affect STAT3 activation by IL-6R and EGFR through JAK or MEK in different HNSCC and response to pharmacologic antagonists. Identifying the potential factors and the regulatory pathways in STAT3 activation has important implications for the development and selection of molecularly targeted therapy in HNSCC. C1 Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Chen, Z (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, 10-5D55,MSC-1419, Bethesda, MD 20892 USA. EM chenz@nidcd.nih.gov RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU Intramural NIH HHS NR 52 TC 96 Z9 98 U1 0 U2 1 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 2006 VL 5 IS 1 BP 8 EP 19 DI 10.1158/1535-7163.MCT-05-0069 PG 12 WC Oncology SC Oncology GA 004SQ UT WOS:000234772900002 PM 16432158 ER PT J AU Rono, B Romer, J Liu, SH Bugge, TH Leppla, SH Kristiansen, PEG AF Rono, B Romer, J Liu, SH Bugge, TH Leppla, SH Kristiansen, PEG TI Antitumor efficacy of a urokinase activation-dependent anthrax toxin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PLASMINOGEN-ACTIVATOR; CAPILLARY MORPHOGENESIS; PROTECTIVE ANTIGEN; MAMMALIAN-CELLS; LETHAL FACTOR; CANCER-CELLS; COLON ADENOCARCINOMAS; MESSENGER-RNA; STROMAL CELLS; TUMOR-GROWTH AB Previously, we have generated a potent prodrug consisting of modified anthrax toxins that is activated by urokinase plasminogen activator (uPA). The cytotoxicity of the drug, PrAg-U2+FP59, is dependent on the presence of receptor-associated uPA activity. Local intradermal administration of PrAg-U2+FP59 adjacent to the tumor nodules in mice with transplanted solid tumors had a potent antitumor effect. In succession of these experiments, we have now investigated the systemic antitumor efficacy of PrAg-U2+FP59. C57BI/6J mice bearing syngenic tumors derived from B16 melanoma, T241 fibrosarcoma, or Lewis lung carcinoma cells were treated with different mass ratios and doses of PrAg-U2+FP59. Tumor volumes were recorded daily by caliper measurements. In some experiments, dexamethasone was coadministered. Our data show a significant antitumor effect of systemic administration of PrAg-U2+FP59 in three syngenic tumor models. Optimal antitumor effect and low toxicity was obtained with a 25:1 mass ratio between the two components (PrAg-U2 and FP59). The experiments show that PrAg-U2+FP59 displays a clear dose-response relationship with regard to both antitumor efficacy and systemic toxicity. Dose-limiting toxicity seemed to be due to activation of the prodrug by uPA and its receptor in the intestinal mucosa. Concurrent treatment with dexamethasone was found to prevent dose-limiting toxicity. Taken together, these data indicate that uPA-activated toxins may be promising candidates for targeted therapy of human cancers that overexpress uPA and its receptor. C1 Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. Univ Copenhagen, Inst Mol Pathol, Copenhagen, Denmark. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD USA. RP Romer, J (reprint author), Rigshosp, Finsen Lab, Strandblvd 49, DK-2100 Copenhagen, Denmark. EM jromer@finsenlab.dk NR 46 TC 28 Z9 30 U1 1 U2 1 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 2006 VL 5 IS 1 BP 89 EP 96 DI 10.1158/1535-7163.MCT-05-0163 PG 8 WC Oncology SC Oncology GA 004SQ UT WOS:000234772900010 PM 16432166 ER PT J AU Feng, Y Zhu, ZY Xiao, XD Choudhry, V Barrett, JC Dimitrov, DS AF Feng, Y Zhu, ZY Xiao, XD Choudhry, V Barrett, JC Dimitrov, DS TI Novel human monoclonal antibodies to insulin-like growth factor (IGH)-II that potently inhibit the IGF receptor type I signal transduction function SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER-CELLS; SOMATOMEDIN RECEPTOR; TUMOR-GROWTH; METASTASIS; BLOCKADE; KINASE; MICE; VIVO AB The insulin-like growth factor (IGF) system plays an important role in a variety of physiologic processes and in diseases such as cancer. Although the role of the IGF system in cancer has been recognized many years ago, components of the system have only recently been targeted and shown to affect cell transformation, proliferation, survival, motility, and migration in tissue cultures and in mouse models of cancer. We have been hypothesizing that targeting IGF-II in addition to blocking its interaction with the IGF receptor type I (IGF-IR) would also allow to block that portion of the signal transduction through the insulin receptor that is due to its interaction with IGF-II. Lowering its level may also not induce upregulation of its production as for IGF-I. Finally, targeting a diffusable ligand as IGF-II may not require penetration of the antibody inside tumors but could shift the equilibrium to IGF-II complexed with antibody so the ligand concentration would decrease in the tumor environment without the need for the antibody to penetrate the tumor. Here, we describe the identification and characterization of three novel anti-IGF-II fully human monoclonal antibodies. They bound with high (subnanomolar) affinity to IGF-II, did not cross-react with IGF-I and insulin, and potently inhibited signal transduction mediated by the IGF-IR interaction with IGF-II. The most potent neutralizer, IgG1 m610, inhibited phosphorylation of the IGF-IR and the insulin receptor, as well as phosphorylation of the downstream kinases Akt and mitogen-activated protein kinase with an IC50 of the order of 1 nmol/L at IGF-II concentration of 10 nmol/L. It also inhibited growth of the prostate cancer cell line DU145 and migration of the breast cancer line cells MCF-7. These results indicate an immunotherapeutic potential of IgG1 m610 likely in combination with other antibodies and anticancer drugs but only further experiments in mouse models of cancer and human clinical trials could evaluate this possibility. C1 NCI, Prot Interact Grp, Nanobiol Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, Sci Applicat Int Corp, Frederick Inc,NIH, Frederick, MD 21702 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, Nanobiol Program, Ctr Canc Res,NIH, Room 105,NIH Bldg 469, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov FU Intramural NIH HHS NR 23 TC 67 Z9 69 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2006 VL 5 IS 1 BP 114 EP 120 DI 10.1158/1535-7163.MCT-05-0252 PG 7 WC Oncology SC Oncology GA 004SQ UT WOS:000234772900013 PM 16432169 ER PT J AU Takahashi, Y Hursting, SD Perkins, SN Wang, TC Wang, TTY AF Takahashi, Y Hursting, SD Perkins, SN Wang, TC Wang, TTY TI Genistein affects androgen-responsive genes through both androgen- and estrogen-induced signaling pathways SO MOLECULAR CARCINOGENESIS LA English DT Article DE androgen receptor; estrogen receptor; isoflavone; prostate cancer; real-time PCR ID PROSTATE-CANCER CELLS; ISOFLAVONES DAIDZEIN; SOYBEAN ISOFLAVONES; ANTIGEN-EXPRESSION; SOY ISOFLAVONE; IN-VITRO; RECEPTOR; GROWTH; LNCAP; ESTRADIOL AB This study examined the mechanisms by which the prostate cancer chemopreventive agent genistein modulates gene expression in LNCaP human prostate cancer cells. Expression of androgen- and estrogen-regulated genes was measured in LNCaP cells cultured in the presence or absence of hormonal stimulation and the presence or absence of genistein. Genistein strongly suppressed basal expression of androgen-responsive gene (ARG) mRNAs, including prostate-specific antigen (PSA) and Ste20-related proline-alanine-rich kinase (SPAK). However, genistein had little or no effect on basal expression of two other ARGs, beta(2)-Microglobulin (B2M) or selenoprotein P (SEPP1). Culturing LNCaP cells in the presence of the synthetic androgen R1881-induced increases in PSA, SPAK, B2M, and SEPP1 mRNA levels. The R1881-induced expression of these genes was uniformly blocked by genistein. For PSA and SPAK, genistein also blocked or downregulated 17 beta-estradiol-induced increases in mRNA expression. These results indicate that genistein selectively alters expression of ARG mRNAs in LNCaP cells through modulation of both androgen- and estrogen-induced signaling pathways. Published 2005 Wiley-Liss, Inc. C1 USDA ARS, Phytonutr Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Food Res Inst, Tsukuba, Ibaraki 305, Japan. Univ Maryland, Nutr Grad Program, College Pk, MD 20742 USA. RP Wang, TTY (reprint author), USDA ARS, Phytonutr Lab, Beltsville Human Nutr Res Ctr, 10300 Baltimore Ave,Bldg 307C,Room 132, Beltsville, MD 20705 USA. NR 44 TC 21 Z9 21 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2006 VL 45 IS 1 BP 18 EP 25 DI 10.1002/mc.20153 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 003SN UT WOS:000234702000003 PM 16299812 ER PT J AU Verma, M Seminara, D Arena, FJ John, C Iwamoto, K Hartmullerl, V AF Verma, M Seminara, D Arena, FJ John, C Iwamoto, K Hartmullerl, V TI Genetic and epigenetic biomarkers in cancer - Improving diagnosis, risk assessment, and disease stratification SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Review ID SQUAMOUS-CELL CARCINOMA; INFLAMMATORY-BOWEL-DISEASE; ABERRANT DNA METHYLATION; TUMOR-SUPPRESSOR GENE; HUMAN COLON-CANCER; COLORECTAL-CANCER; LUNG-CANCER; BREAST-CANCER; PROMOTER METHYLATION; MICROSATELLITE INSTABILITY AB Gene expression patterns change during the initiation, progression, and development of cancer, as a result of both genetic and epigenetic mechanisms. Genetic changes arise due to irreversible changes in the nucleotide sequence, whereas epigenetic changes occur due to changes in chromatin conformation, histone acetylation, and methylation of the CpG islands located primarily in the promoter region of a gene. Both genetic and epigenetic markers can potentially be utilized to identify different stages of tumor development. Several such markers exhibit high sensitivity and specificity for different tumor types and can be assayed in biofluids and other specimens collected by noninvasive technologies. In spite of the availability of large numbers of diagnostic markers, only a few have been clinically validated so far. The current status and the challenges in the field of genetic and epigenetic markers in cancer diagnosis, risk assessment, and disease stratification are discussed. C1 NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. NCI, Clin Epidemiol & Genet Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. US FDA, Rockville, MD 20857 USA. RP Verma, M (reprint author), NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Room EPN 5105,6130 Execut Blvd, Rockville, MD 20852 USA. EM vermam@mail.nih.gov NR 190 TC 19 Z9 20 U1 1 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2006 VL 10 IS 1 BP 1 EP 15 PG 15 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 050ZJ UT WOS:000238129500001 PM 16646573 ER PT J AU Hon, YY Jusko, WJ Zhou, HH Chen, GL Guo, D Zhou, G Spratlin, VE Jann, MW AF Hon, YY Jusko, WJ Zhou, HH Chen, GL Guo, D Zhou, G Spratlin, VE Jann, MW TI Endogenous histamine and cortisol levels in subjects with different histamine N-methyltransferase C314T genotypes - A pilot study SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Article ID INTRACEREBROVENTRICULAR INJECTION; ADRENOCORTICOTROPIC HORMONE; RADIOCHEMICAL MICROASSAY; BIOCHEMICAL-PROPERTIES; PHARMACOGENETICS; POLYMORPHISMS; METABOLISM; RELEASE; CHINESE; MAMMALS AB Background: Histamine N-methyltransferase (HNMT) catalyzes the methylation of histamine and plays an important role in histamine biotransformation in bronchial epithelium. Enzymatic activity of HNMT has been shown to be regulated by genetic factors, including polymorphisms in the HNMT gene. In this pilot study we determined endogenous levels of histamine and cortisol in plasma and whole blood samples from subjects with different genotypes for the HNMT C314T polymorphism, and investigated whether these parameters differed between individuals with the HNMT CC genotype and those with the CT genotype. Methods: Blood samples were collected from 48 unrelated volunteers (36 males, 12 females), aged 21-40 years, who participated in the study. PCR-restriction fragment length polymorphism analysis was used to determine HNMTC314T genotypes. Erythrocyte HNMT activity was determined as well as plasma and whole blood levels of histamine and cortisol. Two-group comparisons of the various parameters were analyzed by Blocked Wilcoxon test and Wilcoxon Rank Sum test as appropriate. Results: Thirty-seven subjects (24 Caucasians, three African Americans, one Middle Eastern, five Indians, three Chinese, and one Filipino) were found to have the homozygous CC genotype. Ten subjects (eight Caucasians, one Middle Eastern, and one Chinese) were heterozygous and one individual (Pakistani) was homozygous for the variant 314T allele. The frequency of HNMTCT heterozygotes in the small Caucasian cohort was 0.125. Median enzyme activity was significantly lower in subjects with the heterozygous CT genotype than in those with the homozygous CC genotype (485 vs 631 U/mL of red blood cells; p=0.023). A broad range of histamine levels in plasma and whole blood was observed for all subjects. Whereas the median plasma histamine level was found to be higher in heterozygotes for the wild-type 314C allele than homozygotes (3.32 vs 2.30 nmol/L; p=0.021), there was no difference between the two groups in histamine levels in whole blood. Cortisol levels were similar between individuals with the homozygous CC genotype and those with the heterozygous CT genotype. Conclusion: Wide variability of plasma and whole-blood histamine levels was observed in subjects with different HNMTC314T genotypes. Endogenous levels of histamine are likely to be affected by various genes and polymorphisms. C1 Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, Atlanta, GA USA. SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. Cent S Univ, Inst Clin Pharmacol, Pharmacogenet Res Inst, Changsha, Hunan, Peoples R China. RP Hon, YY (reprint author), NIH, Clin Pharmacokinet Res Lab, Clin Ctr Pharm Dept, Room 1N-257,Bldg 10,10 Ctr Dr,MSC-1196, Bethesda, MD 20892 USA. EM chon@cc.nih.gov RI Chen, Guo-Lin/E-5559-2015; Jusko, William/G-4885-2015 OI Chen, Guo-Lin/0000-0002-9236-1385; FU NIGMS NIH HHS [R37 GM024211]; PHS HHS [24211] NR 19 TC 4 Z9 4 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2006 VL 10 IS 2 BP 109 EP 114 PG 6 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 051TU UT WOS:000238184700005 PM 16669609 ER PT J AU Srivastava, S AF Srivastava, Sudhir TI Molecular screening of cancer - The future is here SO MOLECULAR DIAGNOSIS & THERAPY LA English DT Article ID CELL LUNG-CANCER; PROMOTER HYPERMETHYLATION; PROSTATE-CANCER; HEPATOCELLULAR-CARCINOMA; GENETIC POLYMORPHISMS; PROGNOSTIC-FACTOR; MARKER DISCOVERY; OVARIAN-CANCER; EXPRESSION; IDENTIFICATION AB The remarkable growth in our knowledge of the biology of cancer is leading to the identification of previously elusive pathways and networks involved in cancer causation. The development of technologies has played a pivotal role in furthering this understanding and appreciation of the complexity of tumorigenesis, and is advancing efforts to fully grasp the biology and exploit the knowledge for improvements in cancer detection, prevention, and therapy. The future of molecular screening, i.e. detection of risk or cancer via molecular determinants, has never been so close to a reality. Molecular assays employed in cancer detection and therapy are likely to revolutionize cancer treatment through individual-based diagnosis and treatment, i.e. personalized medicine. A number of detection techniques, such as the detection of aberrant DNA and RNA, the presence of auto-antibodies in serum or plasma, and protein profiling, are already in limited use for patient stratification for clinical trials and for predicting drug response. C1 NCI, Div Canc Prevent, Canc Biomarkers Res Grp, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), NCI, Div Canc Prevent, Canc Biomarkers Res Grp, 6130 Execut Blvd,Suite 3142, Rockville, MD 20852 USA. EM srivasts@mail.nih.gov NR 51 TC 7 Z9 8 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1177-1062 J9 MOL DIAGN THER JI Mol. Diagn. Ther. PY 2006 VL 10 IS 4 BP 221 EP 230 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 079DD UT WOS:000240154800002 PM 16884325 ER PT J AU Chen, JG Kinyamu, HK Archer, TK AF Chen, JG Kinyamu, HK Archer, TK TI Changes in attitude, changes in latitude: Nuclear receptors remodeling chromatin to regulate transcription SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID HISTONE DEACETYLASE COMPLEXES; MAMMALIAN SWI/SNF COMPLEXES; TUMOR VIRUS PROMOTER; HUMAN BREAST-CANCER; GLUCOCORTICOID-RECEPTOR; IN-VIVO; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; DEPENDENT TRANSCRIPTION; ESTROGEN-RECEPTOR AB Nuclear receptors ( NRs) are a large family of ligand-dependent transcription factors that regulate important physiological processes. To activate or repress genes assembled naturally as chromatin, NRs recruit two distinct enzymatic activities, namely histone-modifying enzymes and ATP-dependent chromatin remodeling complexes, to alter local chromatin structure at target gene promoters. In this review, we examine the functional relationship between ATP-dependent chromatin remodeling complexes and NRs in the context of transcriptional regulation. Using the steroid-responsive mouse mammary tumor virus promoter as a model system, we discuss in detail the molecular mechanisms underlying the recruitment of these complexes and subsequent chromatin structure changes catalyzed by this group of enzymes. In addition, we extend the discussion to other NR-regulated promoters including the pS2 promoter. Finally, we summarize specific principles governing this critical relationship, identify unanswered questions and discuss the potential application of these principles in rational drug design. C1 Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Chromatin & Gene Express Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Chromatin & Gene Express Sect, NIH, 111 Alexander Dr,POB 12233,MD E4-06, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov NR 111 TC 56 Z9 56 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 2006 VL 20 IS 1 BP 1 EP 13 DI 10.1210/me.2005-0192 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 997FH UT WOS:000234230000001 PM 16002433 ER PT J AU Wada, K Hu, L Mores, N Navarro, CE Fuda, H Krsmanovic, LZ Catt, KJ AF Wada, K Hu, L Mores, N Navarro, CE Fuda, H Krsmanovic, LZ Catt, KJ TI Serotonin (5-HT) receptor subtypes mediate specific modes of 5-HT-induced signaling and regulation of neurosecretion in gonadotropin-eleasing hormone neurons SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; CYCLIC-AMP; PULSATILE NEUROSECRETION; PRESYNAPTIC INHIBITION; NEUROPEPTIDE RELEASE; HYPOTHALAMIC NEURONS; AUTOCRINE REGULATION; COUPLED RECEPTORS; ADENYLATE-CYCLASE; TERMINAL DOMAIN AB Serotonin ( 5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol 1,4,5triphosphate/ calcium ( InsP(3)/Ca2+) signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and GnRH release in immortalized GnRH neurons. The high degree of similarity between the signaling and secretory responses elicited by GnRH and 5-HT prompted us to target specific 5-HT receptor subtypes to deconvolute the complex actions of these agonists on signal transduction and GnRH release. Specific mRNA transcripts for 5-HT1A, 5-HT2C, 5-HT4, and 5-HT7 were identified in immortalized GnRH neurons ( GT1-7). The rate of firing of spontaneous action potentials ( APs) by hypothalamic GnRH neurons and cAMP production and pulsatile GnRH release in GT17 cells were profoundly inhibited during activation of the G(i)-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the G(q)-coupled 5-HT2C receptor increased the rate of firing of spontaneous APs, stimulated InsP 3 production and caused a delayed increase in GnRH release. Selective activation of the G(s)-coupled 5-HT4 receptor also increased the rate of firing of APs, stimulated cAMP production, and caused a sustained and robust increase in GnRH release. The ability of 5-HT receptor subtypes expressed in GnRH neurons to activate single or multiple G proteins in a time- and dose-dependent manner differentially regulates the phospholipase C/InsP(3)/Ca2+, and adenylyl cyclase/cAMP signaling pathways, and thereby regulates the frequency and amplitude of pulsatile GnRH release. This process, in conjunction with the modulation of spontaneous electrical activity of the GnRH neuron, contributes to the control of the pulsatile mode of neuropeptide secretion that is characteristic of GnRH neuronal function in vivo and in vitro. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Krsmanovic, LZ (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36, Bethesda, MD 20892 USA. EM lazar@mail.nih.gov FU Intramural NIH HHS NR 69 TC 32 Z9 34 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 2006 VL 20 IS 1 BP 125 EP 135 DI 10.1210/me.2005-0109 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 997FH UT WOS:000234230000010 PM 16109737 ER PT J AU Sparks, SE AF Sparks, SE TI Inherited disorders of glycosylation SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID CONGENITAL DISORDERS; CDG; DEFECT; BIOSYNTHESIS C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sparks, SE (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM ssparks@mail.nih.gov NR 14 TC 6 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2006 VL 87 IS 1 BP 1 EP 7 DI 10.1016/j.ymgme.2005.11.004 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 003NQ UT WOS:000234689300001 PM 16511948 ER PT J AU Schou, M Sovago, J Pike, VW Gulyas, B Bogeso, KP Farde, L Halldin, C AF Schou, M Sovago, J Pike, VW Gulyas, B Bogeso, KP Farde, L Halldin, C TI Synthesis and positron emission tomography evaluation of three norepinephrine transporter radioligands: [C-11]desipramine, [C-11]talopram and [C-11]talsupram SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE norepinephrine transporter; PET; desipramine; talopram; talsupram ID HUMAN-BRAIN; SEROTONIN UPTAKE; UPTAKE INHIBITOR; PET RADIOLIGAND; H-3 NISOXETINE; BINDING-SITES; DESIPRAMINE; RECEPTOR; ANTIDEPRESSANTS; AUTORADIOGRAPHY AB Desipramine (DMI), talopram and talsupram, three of the most potent norepinephrine transporter (NET) inhibitors reported to date, were radiolabeled in high yields and at high specific radioactivity (58-75 GBq/mu mol) by the methylation of nor-precursors with [C-11]methyl triflate. The regional brain distribution of each radioligand following intravenous injection into cynomolgus monkey was examined in vivo with positron emission tomography (PET). For all three radioligands, the regional brain distribution of radioactivity was slightly heterogeneous, with higher uptake of radioactivity in the mesencephalon, thalamus and lower brainstem than in striatum. The rank order of maximal brain radioactivity (as percentage of injected dose) was [C-11]DMI (2.7%) > [C-11]talsupram (1.3%) > [C-11]talopram (0.7%). The appearance of radioactive metabolites in plasma was similar for each radioligand (75-85% of radioactivity in plasma at 45 min). These metabolites were all more polar than their parent radioligand. The data show that these radioligands are inferior to existing radioligands for the study of brain NET with PET in vivo. C1 Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, Karolinska Inst, S-17176 Stockholm, Sweden. Natl Inst Mental Hlth, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. H Lundbeck & Co AS, Copenhagen, Denmark. RP Schou, M (reprint author), Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, Karolinska Inst, S-17176 Stockholm, Sweden. EM magnus.schou@cns.ki.se RI Sovago, Judit/G-7961-2011; Gulyas, Balazs/F-9508-2015 FU Intramural NIH HHS NR 27 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JAN-FEB PY 2006 VL 8 IS 1 BP 1 EP 8 DI 10.1007/s11307-005-0027-y PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 014IV UT WOS:000235474100001 PM 16322935 ER PT J AU An, F Hosokawa, M Chan, CC Caspi, R Medof, ME Lin, F AF An, F Hosokawa, M Chan, CC Caspi, R Medof, ME Lin, F TI DAF deficiency increases susceptivity to Experimental Autoimmune Uveitis (EAU) in mice SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 10th Meeting on Complement in Human Disease CY SEP 09-13, 2005 CL Heidelberg, GERMANY C1 Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. NEI, Dept Immunol, 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2006 VL 43 IS 1-2 MA 159 BP 181 EP 181 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 966LO UT WOS:000232021600172 ER PT J AU Bentley, T Baranyi, L Alving, C Szebeni, J Basta, M AF Bentley, T Baranyi, L Alving, C Szebeni, J Basta, M TI High-dose intravenous immunoglobulin (IVIG) increase survival of rats subjected to experimental hemorrhagic shock SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 10th Meeting on Complement in Human Disease CY SEP 09-13, 2005 CL Heidelberg, GERMANY C1 Walter Reed Army Inst Res, Silver Spring, MD USA. NINDS, 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2006 VL 43 IS 1-2 MA 182 BP 190 EP 190 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 966LO UT WOS:000232021600195 ER PT J AU Hamar, P Basta, M Racz, Z Alper, O Rosivall, L Szebeni, J AF Hamar, P Basta, M Racz, Z Alper, O Rosivall, L Szebeni, J TI Beneficial effects of Angiotensin Converting Enzyme (ACE) inhibition may be partially mediated by inhibition of complement activation in chronic kidney allograft nephropathy in rats SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 10th Meeting on Complement in Human Disease CY SEP 09-13, 2005 CL Heidelberg, GERMANY C1 Hungarian Acad Sci, Nephrol Res Grp, H-1051 Budapest, Hungary. Semmelweis Univ, Inst Pathophysiol, H-1085 Budapest, Hungary. NINDS, NIH, Bethesda, MD 20892 USA. RI Hamar, Peter/A-8996-2010 OI Hamar, Peter/0000-0002-1095-3564 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 2006 VL 43 IS 1-2 MA 183 BP 190 EP 191 PG 2 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 966LO UT WOS:000232021600196 ER PT J AU List, K Bugge, TH Szabo, R AF List, Karin Bugge, Thomas H. Szabo, Roman TI Matriptase: Potent proteolysis on the cell surface SO MOLECULAR MEDICINE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TRANSMEMBRANE SERINE-PROTEASE; BREAST-CANCER CELLS; ICHTHYOSIS VULGARIS; EXPRESSION ANALYSIS; NETHERTON-SYNDROME; EPITHELIAL-CELLS; OVARIAN-CANCER; IN-VITRO; ACTIVATION AB Matriptase is a type II transmembrane serine protease expressed in most human epithelia, where it is coexpressed with its cognate transmembrane inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. Activation of the matriptase zymogen requires sequential N-Terminal cleavage, activation site autocleavage, and transient association with HAI-1. Matriptase has an essential physiological role in profilaggrin processing, comeocyte maturation, and lipid matrix formation associated with terminal differentiation of the oral epithelium and the epidermis, and is also critical for hair follicle growth. Matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression that is unopposed by HAI-1 potently promotes carcinogenesis and metastatic dissemination in animal models. C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU Intramural NIH HHS NR 48 TC 73 Z9 78 U1 2 U2 12 PU FEINSTEIN INSTITUTE MED RES PI MANHASSET PA 350 COMMUNITY DRIVE, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN-MAR PY 2006 VL 12 IS 1-3 BP 1 EP 7 DI 10.2119/2006-00022.List PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 066FX UT WOS:000239216200001 PM 16838070 ER PT J AU Wu, CG Budhu, A Chen, S Zhou, XL Popescu, NC Valerie, K Wang, XW AF Wu, Chuan-ging Budhu, Anuradha Chen, Sheng Zhou, Xiaoling Popescu, Nicholas C. Valerie, Kristoffer Wang, Xin Wei TI Effect of hepatitis C virus core protein on the molecular profiling of human B lymphocytes SO MOLECULAR MEDICINE LA English DT Article ID CD8(+) T-CELLS; GENE-EXPRESSION; II CRYOGLOBULINEMIA; VILLOUS LYMPHOCYTES; DECREASED FREQUENCY; SPLENIC LYMPHOMA; INFECTION; BLOOD; LEADS; SUPPRESSION AB Hepatitis C virus (HCV) core protein features many intriguing properties and plays a pivotal role in cellular immunity, cell growth, apoptosis, cell transformation, and eventually in tumor development. However, the role of B cells, the primary players in the humoral immune response, during HCV infection is largely unknown. To explore the molecular effects of HCV core on human B cells, we conducted gene expression profiling of serial RNA samples from B cells that were infected with adenovirus harboring full-length HCV core protein and beta-galactosiclase as a reference using a microarray platform containing 22,149 human oligo probes. The entire experiment was performed in duplicate in B lymphocytes that were isolated from two individual donors and incubated for up to 3 days after infection with adenovirus expressing HCV core protein to identify dynamic gene expression patterns. Differential expression of representative genes was validated by quantitative RT-PCR. We found that HCV core significantly inhibited B-lymphocyte apoptosis. We showed a dramatic downregulation of MHC class 11 molecules in B cells expressing HCV core, whereas the expression of immunoglobulin genes was not significantly altered. Moreover, genes associated with leukemia and B-lymphoma were consistently upregulated by HCV core. In contrast, downregulation of caspose-1 and caspose-4 was found to be associated with core's ability to prevent B-lymphocyte apoptosis. In summary, we have identified several clusters of genes that are differentially expressed in human B lymphocytes expressing HCV core, suggesting a potential impairment of antigen processing and presentation, which may provide more insights into HCV infection in B lymphocytes. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD USA. Natl Inst Arthritis & Musculoskeletal & Skin Dis, Autoimmun Branch, NIH, Bethesda, MD USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. RP Wu, CG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM-345,29 Lincoln Dr, Bethesda, MD 20892 USA. EM wu@cber.fda.gov; xw3u@nih.gov RI Wang, Xin/B-6162-2009 NR 33 TC 16 Z9 18 U1 0 U2 1 PU FEINSTEIN INSTITUTE MED RES PI MANHASSET PA 350 COMMUNITY DRIVE, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD JAN-MAR PY 2006 VL 12 IS 1-3 BP 47 EP 53 DI 10.2119/2006-00020.Wu PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 066FX UT WOS:000239216200006 PM 16838065 ER PT J AU Galperin, MY Moroz, OV Wilson, KS Murzin, AG AF Galperin, MY Moroz, OV Wilson, KS Murzin, AG TI House cleaning, a part of good housekeeping SO MOLECULAR MICROBIOLOGY LA English DT Review ID NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE; ESCHERICHIA-COLI K-12; MOLECULAR-GRAPHICS PROJECT; ADP-RIBOSE PYROPHOSPHATASE; PENTOSE-PHOSPHATE PATHWAY; GENERAL ENZYMATIC SCREENS; NUDIX HYDROLASES; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; DNA-SYNTHESIS AB Cellular metabolism constantly generates by-products that are wasteful or even harmful. Such compounds are excreted from the cell or are removed through hydrolysis to normal cellular metabolites by various 'house-cleaning' enzymes. Some of the most important contaminants are non-canonical nucleoside triphosphates (NTPs) whose incorporation into the nascent DNA leads to increased mutagenesis and DNA damage. Enzymes intercepting abnormal NTPs from incorporation by DNA polymerases work in parallel with DNA repair enzymes that remove lesions produced by modified nucleotides. House-cleaning NTP pyrophosphatases targeting non-canonical NTPs belong to at least four structural superfamilies: MutT-related ( Nudix) hydrolases, dUTPase, ITPase (Maf/HAM1) and all-alpha NTP pyrophosphatases (MazG). These enzymes have high affinity (K(m)'s in the micromolar range) for their natural substrates (8-oxo-dGTP, dUTP, dITP, 2-oxo-dATP), which allows them to select these substrates from a mixture containing a similar to 1000-fold excess of canonical NTPs. To date, many housecleaning NTPases have been identified only on the basis of their side activity towards canonical NTPs and NDP derivatives. Integration of growing structural and biochemical data on these superfamilies suggests that their new family members cleanse the nucleotide pool of the products of oxidative damage and inappropriate methylation. House-cleaning enzymes, such as 6-phosphogluconolactonase, are also part of normal intermediary metabolism. Genomic data suggest that house-cleaning systems are more abundant than previously thought and include numerous analogous enzymes with overlapping functions. We discuss the structural diversity of these enzymes, their phylogenetic distribution, substrate specificity and the problem of identifying their true substrates. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ York, York Struct Biol Lab, Dept Chem, York YO10 5YW, N Yorkshire, England. MRC, Ctr Prot Engn, Cambridge CB2 2QH, England. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov; agm@mrc-lmb.cam.ac.uk RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS; Medical Research Council [MC_U105192716] NR 94 TC 121 Z9 124 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2006 VL 59 IS 1 BP 5 EP 19 DI 10.1111/j.1365-2958.2005.04950.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 991QM UT WOS:000233828700002 PM 16359314 ER PT J AU Guillier, M Gottesman, S AF Guillier, M Gottesman, S TI Remodelling of the Escherichia coli outer membrane by two small regulatory RNAs SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRANSCRIPTIONAL ACTIVATOR; COMPARATIVE GENOMICS; RIBOSOME BINDING; NONCODING RNAS; ANTISENSE RNA; IDENTIFICATION; EXPRESSION; SYSTEM; PROTEIN; HFQ AB Small non-coding RNAs that play important regulatory roles exist in numerous organisms. In Escherichia coli, about 60 small RNAs have been found and those that have been studied are involved in the response and adaptation to different stresses. RygA and RygB, two of these small RNAs, were identified on the basis of their conservation between different species and their ability to bind Hfq. They are adjacent on the chromosome and have sequence similarity at their 5' and 3' ends but distinct central regions, suggesting that they could regulate the expression of both common and distinct genes. A screen using a multicopy E. coli library led to identification of the response regulator OmpR and its associated sensor kinase EnvZ as positive regulators of rygA and rygB transcription. Therefore, RygA and RygB were renamed OmrA and OmrB respectively (for OmpR- regulated sRNAs A and B). When expressed at high levels, OmrA and OmrB RNAs negatively regulate the expression of several genes encoding multiple outer membrane proteins, including cirA, fecA, fepA and ompT. Taken together, these data suggest that OmrA and OmrB participate in the regulation of outer membrane composition in response to environmental conditions. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM susang@helix.nih.gov FU Intramural NIH HHS NR 60 TC 140 Z9 148 U1 0 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2006 VL 59 IS 1 BP 231 EP 247 DI 10.1111/j.1365-2958.2005.04929.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 991QM UT WOS:000233828700019 PM 16359331 ER PT J AU Edgar, R Biek, D Yarmolinsky, M AF Edgar, R Biek, D Yarmolinsky, M TI P1 plasmid partition: in vivo evidence for the ParA- and ParB-mediated formation of an anchored parS complex in the absence of a partner parS SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI CHROMOSOME; ATP-BINDING SITE; DNA SEGREGATION; BACTERIAL MITOSIS; PROTEIN; INTEGRATION; REPLICATION; MECHANISM; TRANSCRIPTION; CONFORMATION AB ParA and ParB proteins and cis-acting site, parS, are required to partition plasmid P1 faithfully to daughter cells. The process may initiate from plasmids paired by ParB at which recruited ParA then acts to effect the separation. We previously reported evidence for ParB-mediated pairing of parS sites on plasmids in the absence of ParA. In DNA gyrase-inhibited cells, the pairing prevented diffusion of transcription-generated positive supercoils. This supercoil trapping was almost entirely in plasmid dimers, where the location of the parS sites in cis facilitated their pairing. Here we show that the addition of ParA blocked supercoil diffusion also in plasmid monomers. The possibility that this result is attributed to an enhancement by ParA of ParB-mediated pairing in trans is consistent with our finding that ParA appeared to partially suppress the pairing defect of two mutant ParB proteins. However, enhanced pairing alone could not account for the diffusion barrier in plasmid monomers; it was manifest in monomers even when they were largely devoid of partners in the same cell. Apparently, ParA altered the ParB-parS complex such that it could no longer swivel, most likely by anchoring it, a reaction of probable relevance to partition. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Biek, D (reprint author), Appl Biosyst Inc, 850 Lincoln Ctr Dr,MS 404-1, Foster City, CA 94404 USA. EM donald.biek@appliedbiosystems.com FU Intramural NIH HHS NR 43 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2006 VL 59 IS 1 BP 276 EP 287 DI 10.1111/j.1365-2958.2005.04933.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 991QM UT WOS:000233828700022 PM 16359334 ER PT J AU Boylan, JA Hummel, CS Benoit, S Garcia-Lara, J Treglown-Downey, J Crane, EJ Gherardini, FC AF Boylan, JA Hummel, CS Benoit, S Garcia-Lara, J Treglown-Downey, J Crane, EJ Gherardini, FC TI Borrelia burgdorferi bb0728 encodes a coenzyme A disulphide reductase whose function suggests a role in intracellular redox and the oxidative stress response SO MOLECULAR MICROBIOLOGY LA English DT Article ID BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; NADH OXIDASE; DNA-DAMAGE; SPIROCHETE; SEQUENCE; GLUTATHIONE; PEROXIDASE; MYCOTHIOL; PATHWAYS AB The cellular responses of Borrelia burgdorferi to reactive oxygen species (ROS) encountered during the different stages of its infective cycle are poorly understood. Few enzymes responsible for protecting proteins, DNA/RNA and lipids from damage by ROS have been identified and characterized. Data presented here suggest that bb0728 encodes an enzyme involved in this process. Biochemical analyses on purified recombinant BB0728 indicated that it functioned as a coenzyme A disulphide reductase (CoADR) (specific activity approximate to 26 units per mg of protein). This enzyme was specific for coenzyme A (CoA) disulphide, required NADH and had no significant activity against other disulphides, such as oxidized glutathione or thioredoxin. The high intracellular concentration of reduced CoA (CoASH) in B. burgdorferi cells (similar to 1 mM) and absence of glutathione suggest that CoA is the major low-molecular-weight thiol in this spirochete. Interestingly, CoASH was able to reduce H2O2 and be regenerated by CoADR suggesting one role for the system may be to protect B. burgdorferi from ROS. Further, mobility-shift assays and transcriptional fusion data indicated that bb0728 was positively regulated by the Borrelia oxidative stress response regulator, BosR. Taken together, these data suggest a role for BB0728 in intracellular redox and the oxidative stress response in B. burgdorferi. C1 NIAID, Lab Zoonit Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Pomona Coll, Dept Chem, Claremont, CA 91711 USA. Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England. Univ So Calif, Los Angeles, CA 90089 USA. RP NIAID, Lab Zoonit Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fgherardini@niaid.nih.gov OI Crane, Edward/0000-0002-9910-9502 FU Intramural NIH HHS NR 38 TC 42 Z9 43 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2006 VL 59 IS 2 BP 475 EP 486 DI 10.1111/j.1365-2958.2005.04963.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 996GR UT WOS:000234162900011 PM 16390443 ER PT J AU Grieshaber, NA Grieshaber, SS Fischer, ER Hackstadt, T AF Grieshaber, NA Grieshaber, SS Fischer, ER Hackstadt, T TI A small RNA inhibits translation of the histone-like protein Hc1 in Chlamydia trachomatis SO MOLECULAR MICROBIOLOGY LA English DT Article ID SM-LIKE PROTEIN; DEVELOPMENTAL CYCLE; GENOME SEQUENCE; ESCHERICHIA-COLI; GENE; HFQ; REGULATOR; DNA; PSITTACI AB The chromatin of chlamydial elementary bodies (EBs) is stabilized by proteins with sequence homology to eukaryotic H1. These histone homologues, termed Hc1 and Hc2, are expressed only during the late stages of the chlamydial life cycle concomitant with the reorganization of reticulate bodies (RBs) into metabolically inactive EBs. Hc1 and Hc2 play a major role in establishment of nucleoid structure as well as in downregulation of gene expression as RBs differentiate back to EBs. The effects of Hc1 on gene expression patterns requires that chlamydiae strictly control Hc1 activity. Hc1 expression and activity are thus regulated transcriptionally as well as post-transcriptionally. We describe here a small regulatory RNA (sRNA) that acts as an additional checkpoint to negatively regulate Hc1 synthesis. Coexpression of the sRNA with hctA, the gene that encodes Hc1, in Escherichia coli inhibited Hc1 translation but did not affect hctA mRNA transcription or stability. IhtA (inhibitor of hctA translation) was present only in purified RBs while Hc1 was present only in purified EBs. During infection IhtA, but not Hc1, was present in RBs and was downregulated while Hc1 was upregulated upon RB to EB differentiation. Thus, we propose that IhtA is part of a global regulatory circuit that controls differentiation of RBs to EBs during the chlamydial life cycle. C1 NIAID, Rocky Mt Labs, Host Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Core Facil, NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Rocky Mt Labs, Host Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU Intramural NIH HHS NR 31 TC 48 Z9 48 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2006 VL 59 IS 2 BP 541 EP 550 DI 10.1111/j.1365-2958.2005.04949.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 996GR UT WOS:000234162900016 PM 16390448 ER PT J AU Calcagno, AM Ludwig, JA Fostel, JM Gottesman, MM Ambudkar, SV AF Calcagno, Anna Maria Ludwig, Joseph A. Fostel, Jennifer M. Gottesman, Michael M. Ambudkar, Suresh V. TI Comparison of drug transporter levels in normal colon, colon cancer, and Caco-2 cells: Impact on drug disposition and discovery SO MOLECULAR PHARMACEUTICS LA English DT Article DE gene expression; ATP-binding cassette (ABC) transporters; solute carriers; colon; Caco-2 cells; Affymetrix HG-U133A GeneChip AB A critical step in early phase drug development is the determination of oral bioavailability. In part, the ability to predict whether a drug will be effectively transported across the gastrointestinal mucosa can be estimated from the physicochemical properties of the compound. Although advancements through rational drug design have more correctly predicted bioavailability, considerable variability remains to be explained. Transporter expression throughout the gastrointestinal tract may explain much of this variation. ATP-binding cassette (ABC) transporters were the first family of transporters identified to modify bioavailability. More recently, the solute carrier family has also been shown to alter the pharmacokinetic profile of drugs. Currently, the Caco-2 human colon carcinoma cell line is often used by the pharmaceutical industry to evaluate intestinal absorption of drugs; however, in vivo/in vitro permeabilities with carrier mediated drugs do not correlate well, suggesting that Caco-2 transporter expression varies from that of the small intestine. With this is mind, we integrated U133A GeneChip expression data from the NCBIs Gene Expression Omnibus (GEO) collection and then compared the expression pattern of Caco-2 cells to normal colon to determine if the Caco-2 cell line is a reliable model for colonic delivery. Furthermore, transporter expression of Caco-2 cells was compared to that of human colon tumors to assess whether this cell line could be useful to predict drug absorption for colon cancer. Our analysis shows that the expression pattern for Caco-2 cells closely resembles the gene expression profile of transporters within the normal colon, suggesting that this cell line may serve as an in vitro model of colonic drug adsorption. However, the molecular "fingerprint" of Caco-2 was distinctly different from tumor samples, indicating that the Caco-2 model would unlikely predict accurate drug absorption for colon cancer sites. C1 [Calcagno, Anna Maria; Ludwig, Joseph A.; Fostel, Jennifer M.; Gottesman, Michael M.; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Calcagno, AM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, Natl Inst Hlth, Bldg 37,Room 2120,37 Convent Dr MSC4256, Bethesda, MD 20892 USA. EM calcagnoa@mail.nih.gov RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU National Cancer Institute; NIH; NIGMS Pharmacology Research Associate (PRAT) FX We thank Drs. Joseph A. Ware, In-Wha Kim, and Zuben E. Sauna for critically reviewing this manuscript and providing useful suggestions. The authors also thank Dr. Hiroyuki Mano for providing us with the colon cancer data files. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH. A.M.C. was supported by the NIGMS Pharmacology Research Associate (PRAT) Program. NR 32 TC 30 Z9 33 U1 0 U2 10 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 2006 VL 3 IS 1 BP 87 EP 93 DI 10.1021/mp050090k PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JG UT WOS:000203539200010 PM 16686373 ER PT J AU Kwon-Chung, KJ Wickes, BL AF Kwon-Chung, Kyung J. Wickes, Brian L. BE Heitman, J Filler, SG Edwards, JE Mitchell, AP TI The Conversion from Classical Studies in Fungal Pathogenesis to the Molecular Era SO MOLECULAR PRINCIPLES OF FUNGAL PATHOGENESIS LA English DT Article; Book Chapter ID TUMEFACIENS-MEDIATED TRANSFORMATION; CANDIDA-ALBICANS STRAINS; HIGH-EFFICIENCY TRANSFORMATION; POLYMERASE-CHAIN-REACTION; TARGETED GENE DISRUPTION; HYGROMYCIN-B RESISTANCE; SELECTABLE MARKER URA3; DOUBLE-STRANDED-RNA; CRYPTOCOCCUS-NEOFORMANS; HISTOPLASMA-CAPSULATUM C1 [Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Wickes, Brian L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78284 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 167 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-577-6 PY 2006 BP 49 EP + PG 23 WC Infectious Diseases; Mycology; Pathology SC Infectious Diseases; Mycology; Pathology GA BPD96 UT WOS:000278639300006 ER PT J AU Walsh, TJ Roilides, E Cortez, K Lyman, C AF Walsh, Thomas J. Roilides, Emmanuel Cortez, Karoll Lyman, Caron BE Heitman, J Filler, SG Edwards, JE Mitchell, AP TI Molecular Immunopathogenesis of Innate Host Defense against Chronic Disseminated (Hepatosplenic) Candidiasis SO MOLECULAR PRINCIPLES OF FUNGAL PATHOGENESIS LA English DT Article; Book Chapter ID GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTOR; ANTIFUNGAL ACTIVITY; HUMAN MONOCYTES; FUNGAL-INFECTIONS; INTERFERON-GAMMA; CANCER-PATIENTS; TGF-BETA; ALBICANS; INTERLEUKIN-10 C1 [Walsh, Thomas J.; Roilides, Emmanuel; Cortez, Karoll; Lyman, Caron] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-577-6 PY 2006 BP 583 EP 588 PG 6 WC Infectious Diseases; Mycology; Pathology SC Infectious Diseases; Mycology; Pathology GA BPD96 UT WOS:000278639300040 ER PT J AU Insel, TR Scolnick, EM AF Insel, TR Scolnick, EM TI Cure therapeutics and strategic prevention: raising the bar for mental health research SO MOLECULAR PSYCHIATRY LA English DT Article DE recovery; remission; prevention; pathophysiology; drug development ID COMORBIDITY SURVEY REPLICATION; MAJOR DEPRESSIVE DISORDER; FOLLOW-UP; SCHIZOPHRENIA; POLYMORPHISM; REMISSION; RECOVERY; PREVALENCE; PREDICTION; RATIONALE AB Mental disorders cause more disability than any other class of medical illness in Americans between ages 15 and 44 years. The suicide rate is higher than the annual mortality from homicide, AIDS, and most forms of cancer. In contrast to nearly all communicable and most non-communicable diseases, there is little evidence that the morbidity and mortality from mental disorders have changed in the past several decades. Mental health advocates, including psychiatric researchers, have pointed to stigma as one of the reasons for the lack of progress with mental illnesses relative to other medical illnesses. This review considers how the expectations and goals of the research community have contributed to this relative lack of progress. In contrast to researchers in cancer and heart disease who have sought cures and preventions, biological psychiatrists in both academia and industry have set their sights on incremental and marketable advances, such as drugs with fewer adverse effects. This essay argues for approaches that can lead to cures and strategies for prevention of schizophrenia and mood disorders. C1 NIMH, Bethesda, MD 20892 USA. MIT, Broad Inst, Cambridge, MA USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. RP Insel, TR (reprint author), NIMH, Room 8235,6001 Execut Blvd, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 40 TC 118 Z9 119 U1 1 U2 6 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 2006 VL 11 IS 1 BP 11 EP 17 DI 10.1038/sj.mp.4001777 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 993QZ UT WOS:000233971300005 PM 16355250 ER PT J AU del Sol, A Fujihashi, H Amoros, D Nussinov, R AF del Sol, Antonio Fujihashi, Hirotomo Amoros, Dolors Nussinov, Ruth TI Residues crucial for maintaining short paths in network communication mediate signaling in proteins SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE allosteric communications; conserved interconnectivity determinants; long-range interactions; network; robustness ID GLYCOGEN-PHOSPHORYLASE; HIV-1 PROTEASE; ALLOSTERIC COMMUNICATION; CONVERTING TRYPSIN; COUPLED RECEPTORS; SUBSTRATE-BINDING; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; T-STATE; SITE AB Here, we represent protein structures as residue interacting networks, which are assumed to involve a permanent flowof information between amino acids. By removal of nodes from the protein network, we identify fold centrally conserved residues, which are crucial for sustaining the shortest pathways and thus play key roles in long-range interactions. Analysis of seven protein families (myoglobins, G-protein-coupled receptors, the trypsin class of serine proteases, hemoglobins, oligosaccharide phosphorylases, nuclear receptor ligand-binding domains and retroviral proteases) confirms that experimentally many of these residues are important for allosteric communication. The agreement between the centrally conserved residues, which are key in preserving short path lengths, and residues experimentally suggested to mediate signaling further illustrates that topology plays an important role in network communication. Protein folds have evolved under constraints imposed by function. To maintain function, protein structures need to be robust to mutational events. On the other hand, robustness is accompanied by an extreme sensitivity at some crucial sites. Thus, here we propose that centrally conserved residues, whose removal increases the characteristic path length in protein networks, may relate to the system fragility. C1 Fujirebio Inc, Bioinformat Res Univ, Res & Dev Div, Hachioji, Tokyo 1920031, Japan. NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21701 USA. Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP del Sol, A (reprint author), Fujirebio Inc, Bioinformat Res Univ, Res & Dev Div, 51 Komiya Cho, Hachioji, Tokyo 1920031, Japan. EM ao-mesa@fujirebio.co.jp FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 56 TC 104 Z9 104 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PY 2006 VL 2 AR 2006.0019 DI 10.1038/msb4100063 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122RX UT WOS:000243245400019 PM 16738564 ER PT J AU Kohn, KW Aladjem, MI AF Kohn, Kurt W. Aladjem, Mirit I. TI Circuit diagrams for biological networks SO MOLECULAR SYSTEMS BIOLOGY LA English DT Editorial Material ID REPRESENTATION; SYSTEMS C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU Intramural NIH HHS NR 8 TC 10 Z9 10 U1 0 U2 0 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 2006 VL 2 AR 2006.0002 DI 10.1038/msb4100044 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122RX UT WOS:000243245400004 PM 16738549 ER PT J AU Kohn, KW Aladjem, MI Kim, S Weinstein, JN Pommier, Y AF Kohn, Kurt W. Aladjem, Mirit I. Kim, Sohyoung Weinstein, John N. Pommier, Yves TI Depicting combinatorial complexity with the molecular interaction map notation SO MOLECULAR SYSTEMS BIOLOGY LA English DT Review DE EGFR; epidermal growth factor receptor; molecular interaction maps; network diagrams; signaling networks ID BIOLOGY MARKUP LANGUAGE; GROWTH-FACTOR RECEPTOR; CELL-CYCLE; SYSTEMS BIOLOGY; LIPID RAFTS; BIOREGULATORY NETWORKS; SIGNAL-TRANSDUCTION; SIMULATION; DYNAMICS; MODEL AB To help us understand how bioregulatory networks operate, we need a standard notation for diagrams analogous to electronic circuit diagrams. Such diagrams must surmount the difficulties posed by complex patterns of protein modifications and multiprotein complexes. To meet that challenge, we have designed the molecular interaction map (MIM) notation (http://discover.nci.nih.gov/mim/). Here we show the advantages of the MIM notation for three important types of diagrams: (1) explicit diagrams that define specific pathway models for computer simulation; (2) heuristic maps that organize the available information about molecular interactions and encompass the possible processes or pathways; and (3) diagrams of combinatorially complex models. We focus on signaling from the epidermal growth factor receptor family (EGFR, ErbB), a network that reflects the major challenges of representing in a compact manner the combinatorial complexity of multimolecular complexes. By comparing MIMs with other diagrams of this network that have recently been published, we show the utility of the MIM notation. These comparisons may help cell and systems biologists adopt a graphical language that is unambiguous and generally understood. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM kohnk@dc37a.nci.nih.gov RI Aladjem, Mirit/G-2169-2010; OI Aladjem, Mirit/0000-0002-1875-3110; Kim, Sohyoung/0000-0002-6140-7918 FU Intramural NIH HHS NR 40 TC 28 Z9 28 U1 0 U2 0 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 2006 VL 2 AR 51 DI 10.1038/msb4100088 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122RX UT WOS:000243245400052 PM 17016517 ER PT J AU Manickan, E Smith, JS Tian, J Eggerman, TL Lozier, JN Muller, J Byrnes, AP AF Manickan, E Smith, JS Tian, J Eggerman, TL Lozier, JN Muller, J Byrnes, AP TI Rapid Kupffer cell death after intravenous injection of adenovirus vectors SO MOLECULAR THERAPY LA English DT Article DE Kupffer cells; gene therapy; adenoviridae; genetic vectors; necrosis; electron microscopy; intravenous injections; liver; lung ID MEDIATED GENE-TRANSFER; IN-VIVO; LACTATE-DEHYDROGENASE; FOREIGN PARTICLES; NONHUMAN-PRIMATES; MICE; RESPONSES; LIVER; MACROPHAGES; ACTIVATION AB When adenovirus vectors are injected intravenously, they are quickly taken up by Kupffer cells in the liver. We report that this causes rapid necrosis of Kupffer cells in mice at doses of 10(11) particles/kg or higher. By 10 min after intravenous vector injection, Kupffer cells were permeable to propidium iodide and trypan blue. This coincided with a sharp rise in serum lactate dehydrogenase. Ultrastructural examination showed degeneration of Kupffer cells, including complete disappearance of chromatin by I h. After an initial intravenous injection of vector, dead Kupffer cells were unable to take up a second dose of vector, and hepatic transgene expression from the second dose was augmented. Death of Kupffer cells did not affect serum levels of IL-6 or IL-12. There was no immediate change in the number of Kupffer cells in the liver, but a significant decline was found by 4 h after injection of vector. Interestingly, substantial numbers of vector-containing Kupffer cells were found in pulmonary capillaries, indicating that they had been swept out of the liver. Together these results show that an intravenous injection of adenovirus vector causes synchronous and surprisingly rapid Kupffer cell death. C1 US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Manickan, E (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM-725, Bethesda, MD 20892 USA. EM byrnesa@cber.fda.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 38 TC 82 Z9 82 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2006 VL 13 IS 1 BP 108 EP 117 DI 10.1016/j.ymthe.2005.08.007 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 001PK UT WOS:000234548600015 PM 16198149 ER PT J AU Zhao, YB Zheng, ZL Cohen, CJ Gattinoni, L Palmer, DC Restifo, NP Rosenberg, SA Morgan, RA AF Zhao, YB Zheng, ZL Cohen, CJ Gattinoni, L Palmer, DC Restifo, NP Rosenberg, SA Morgan, RA TI High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation SO MOLECULAR THERAPY LA English DT Article DE mRNA; electroporation; transfection; T lymphocytes ID GENE-TRANSFER; TUMOR-ANTIGEN; IN-VITRO; ANTITUMOR LYMPHOCYTES; METASTATIC MELANOMA; CANCER REGRESSION; EFFECTOR FUNCTION; DENDRITIC CELLS; EXPRESSION; DELIVERY AB The use of nonviral gene transfer methods in primary lymphocytes has been hampered by low gene transfer efficiency and high transfection-related toxicity. In this report, high gene transfection efficiency with low transfection-related toxicity was achieved by electroporation using in vitro-transcribed mRNA. Using these methods, > 90% transgene expression with > 80% viable cells was observed in stimulated primary human and murine T lymphocytes transfected with GFP or mCD62L. Electroporation of unstimulated human PBMCs or murine splenocytes with GFP RNA yielded 95 and 56% GFP(+) cells, respectively. Electroporation of mRNA for NY-ESO-1, MART-1, and p53 antigen-specific TCRs into human T lymphocytes redirected these lymphocytes to recognize melanoma cell lines in an MHC-restricted manner. The onset of gene expression was rapid (within 30 min) and durable (up to 7 days postelectroporation) using both GFP and TCR-mediated recognition of target cells. There was no adverse effect observed on the T lymphocytes subjected to RNA electroporation evaluated by cell growth rate, annexin-V staining of apoptotic cells, BrdU incorporation, tumor antigen-specific recognition or antigen-specific TCR affinity. The results of this study indicate that mRNA electroporation provides a powerful tool to introduce genes into both human and murine primary T lymphocytes. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Palmer, Douglas/B-9454-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 30 TC 111 Z9 113 U1 2 U2 7 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 2006 VL 13 IS 1 BP 151 EP 159 DI 10.1016/j.ymthe.2005.07.688 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 001PK UT WOS:000234548600020 PM 16140584 ER PT J AU Slobounov, S Wu, T Hallett, M AF Slobounov, S Wu, T Hallett, M TI Neural basis subserving the detection of postural instability: An fMRI study SO MOTOR CONTROL LA English DT Article DE brain activations; BOLD signal; postural stability; perception of postural instability ID EVENT-RELATED FMRI; PARIETAL CORTEX; BASAL GANGLIA; BIOLOGICAL MOTION; ANTERIOR CINGULATE; DECISION-MAKING; MACAQUE MONKEY; PERCEPTION; CEREBELLAR; MOVEMENT AB Human upright posture is a product of a complex dynamic system that relies on integration of input from multimodal sensory sources. Extensive research has explored the role of visual, vestibular, and somatosensory systems in the control of upright posture. However, the role of higher cognitive function in a participant's assessment of postural stability has been less studied. In previous research, we showed specific neural activation patterns in EEG associated with recognition of unstable postures in young healthy participants. Similar EEG patterns have been recently observed in regulation of posture equilibrium in dynamic stances. This article evaluates participants' postural stability in dynamic stances and neural activation patterns underlying visual recognition of unstable postures using event-related functional MRI (fMRI). Our results show that the "stable" participants were successful in recognition of unstable postures of a computer-animated body model and experienced egocentric motion. Successful recognition of unstable postures in these participants induces activation of distinct areas of the brain including bilateral parietal cortex, anterior cingulate cortex, and bilateral cerebellum. In addition, significant activation is observed in basal ganglia (caudate nucleus and putamen) but only during perception of animated postures. Our findings suggest the existence of modality-specific distributed activation of brain areas responsible for detection of postural instability. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA. RP Slobounov, S (reprint author), NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 83 TC 19 Z9 20 U1 1 U2 4 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1087-1640 EI 1543-2696 J9 MOTOR CONTROL JI Motor Control PD JAN PY 2006 VL 10 IS 1 BP 69 EP 89 PG 21 WC Neurosciences; Sport Sciences SC Neurosciences & Neurology; Sport Sciences GA 009KQ UT WOS:000235111200006 PM 16571908 ER PT B AU Hallett, M AF Hallett, Mark BE Latash, ML Lestieene, F TI The role of the motor cortex in motor learning SO Motor Control and Learning LA English DT Proceedings Paper CT 4th Conference on Progress in Motor Control CY 2003 CL Caen, FRANCE ID POSITRON-EMISSION-TOMOGRAPHY; SKILL; CONSOLIDATION; CEREBELLUM; MODULATION; IMPLICIT; PET; STIMULATION; ACQUISITION; PLASTICITY AB The motor cortex is clearly more than a simple executor of motor commands and is likely involved with different aspects of motor learning. The motor cortex shows considerable plasticity, and both excitability and amount of territory devoted to a muscle or to a specific task can expand or shrink depending oil the amount of use. There are also short-term increases in motor cortex activity when learning new tasks. In the serial reaction time task (SRTT), as demonstrated by transcranial magnetic stimulation (TMS), EEG, and positron emission tomography, the motor cortex is involved in the implicit phase of motor learning and declines in activity during the explicit phase. In learning to increase pinch force and pinch acceleration between index and thumb, the motor evoked potential (MEP) from TMS increases during the early stage of learning, but then declines even though the behavioral change is maintained. In learning a bimanual task, there is a transient increase in EEG coherence between the two hemispheres at the time of the learning. What function this short-term increase in motor cortex activity serves is not certain. It has recently been established that motor learning goes through a phase of consolidation and becomes more secure simply with the passage of time. This was first demonstrated while adapting to making accurate movements in a force field. Neuroimaging studies with these same movements in a force field show a transient increase in motor cortex activity during the learning phase. In our laboratory, we have studied consolidation of the learning to increase pinch force and acceleration. Consolidation is disrupted by 1 Hz repetitive TMS of the motor cortex if done immediately after learning, but not after a rest of 6 hours. This demonstrates a role of the motor cortex in consolidation. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 28 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-25390-4 PY 2006 BP 89 EP 95 DI 10.1007/0-387-28287-4_8 PG 7 WC Psychology, Developmental; Neurosciences; Psychology, Experimental SC Psychology; Neurosciences & Neurology GA BEJ05 UT WOS:000237414200008 ER PT J AU Chiba-Falek, O Lopez, GJ Nussbaum, RL AF Chiba-Falek, Ornit Lopez, Grisel J. Nussbaum, Robert L. TI Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients SO MOVEMENT DISORDERS LA English DT Article DE alpha-synuclein; Parkinson disease; SNCA-mRNA; real-time PCR ID LEWY BODY; LOCUS TRIPLICATION; EXPRESSION; MUTATION; DUPLICATION; DEMENTIA; BODIES AB Lewy bodies, the pathological hallmark of Parkinson's disease (PD), consist largely of alpha-synuclein, a 14.5-kDa presynaptic neuronal protein implicated in familial PD. An increased copy number and elevated expression of wild-type a-synuclein (SNCA) has been shown to cause early-onset familial PD. However, it is not clear whether increased a-synuclein expression also plays a role in the pathogenesis of sporadic disease. In the current study, we analyzed the levels of SNCA-mRNA in affected brains of sporadic PD patients. We compared the levels of steady state SNCA-mRNA in 7 sporadic PD brain samples and 7 normal controls using real-time polymerase chain reaction of RNA extracted from mid-brain tissue, including the substantia nigra. Despite that there is neuronal loss in the substantia nigra of PD brains, overall the SNCA-mRNA levels were increased in PD brains an average of nearly fourfold over normal control mid-brain, although there was much greater variability in samples from PD patients compared to controls. Frontal cortex samples from selected individuals were also analyzed. SNCA-mRNA levels were not significantly changed in PD frontal cortex compared to controls. These results suggest that elevated expression levels of SNCA-mRNA are found in the affected regions of PD brain and support the hypothesis that increases in a-synuclein expression is associated, among other factors, with the development of sporadic PD. (C) 2006 Movement Disorder Society. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr MSC 4472, Bethesda, MD 20892 USA. EM rlnuss@mail.nih.gov FU NIMH NIH HHS [MH68855] NR 20 TC 76 Z9 76 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. PY 2006 VL 21 IS 10 BP 1703 EP 1708 DI 10.1002/mds.21007 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 101MQ UT WOS:000241745300020 PM 16795004 ER PT J AU Henkel, K Danek, A Grafman, J Butman, J Kassubek, J AF Henkel, Karsten Danek, Adrian Grafman, Jordan Butman, John Kassubek, Jan TI Head of the caudate nucleus is most vulnerable in chorea-acanthocytosis: A voxel-based morphometry study SO MOVEMENT DISORDERS LA English DT Article DE neuroacanthocytosis; voxel-based morphometry; brain atrophy ID HUNTINGTONS-DISEASE; BASAL GANGLIA; NEUROACANTHOCYTOSIS; BRAIN; CIRCUITS; PROTEIN; GENE; MRI AB Chorea-acanthocytosis (ChAc; OMIM 200150) is a rare autosomal recessive disease with dysfunction of the erythrocyte membrane, presenting with acanthocytes and neurological manifestations characterized by progressive hyperkinesias (chorea, dystonia) and neuropsychological impairment. Damage to the basal ganglia was described previously in neuropathological and neuroimaging investigations. We analyzed high-resolution MRI of six ChAc patients with mutations in the VPS13A gene (median age, 37 years; mean time since clinical onset, 13 years) with respect to regional atrophy by use of the observer-independent technique of voxel-based morphometry in comparison to 15 age-matched healthy controls. Additionally, global brain atrophy was determined using the standardized brain parenchymal fraction (BPF) method. A robust regional reduction of gray matter density was observed in the head of the caudate nucleus bilaterally and was nearly symmetrical (P < 0.001, corrected for small volumes). No additional gray matter changes were found. In the BPF analysis, there was no significant global brain atrophy. The predilection of atrophy in the head of the caudate nucleus, as suggested by our results, argues for a particular vulnerability of this part of the striatum in ChAc and is in agreement with pronounced neuropsychological disturbances that are thought to rely on these regions. (C) 2006 Movement Disorder Society. C1 Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. Univ Munich, Dept Neurol, D-8000 Munich, Germany. Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Henkel, K (reprint author), Univ Ulm, Dept Neurol, Oberer Eselsberg 45, D-89081 Ulm, Germany. EM karsten.henkel@gmx.de RI Butman, John/A-2694-2008; Danek, Adrian/G-7339-2011; Kassubek, Jan/F-2774-2015; OI Danek, Adrian/0000-0001-8857-5383; Grafman, Jordan H./0000-0001-8645-4457; Butman, John/0000-0002-1547-9195 NR 23 TC 24 Z9 24 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PY 2006 VL 21 IS 10 BP 1728 EP 1731 DI 10.1002/mds.21046 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 101MQ UT WOS:000241745300025 PM 16874760 ER PT J AU Hardy, J AF Hardy, John TI No definitive evidence for a role for the environment in the etiology of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Letter ID RISK C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 9 TC 5 Z9 5 U1 0 U2 0 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. PY 2006 VL 21 IS 10 BP 1790 EP 1791 DI 10.1002/mds.21067 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 101MQ UT WOS:000241745300047 PM 16941458 ER PT J AU Deuschl, G Herzog, J Kleiner-Fisman, G Kubu, C Lozano, AM Lyons, KE Rodriguez-Oroz, MC Tamma, F Troster, AI Vitek, JL Volkmann, J Voon, V AF Deuschl, G Herzog, J Kleiner-Fisman, G Kubu, C Lozano, AM Lyons, KE Rodriguez-Oroz, MC Tamma, F Troster, AI Vitek, JL Volkmann, J Voon, V TI Deep brain stimulation: Postoperative issues SO MOVEMENT DISORDERS LA English DT Review DE deep brain stimulation; Parkinson's disease; postoperative management ID SUBTHALAMIC NUCLEUS STIMULATION; ADVANCED PARKINSONS-DISEASE; TERM-FOLLOW-UP; BILATERAL PALLIDAL STIMULATION; CHRONIC THALAMIC-STIMULATION; HIGH-FREQUENCY STIMULATION; DBS REPLACES LEVODOPA; VOICE TREATMENT LSVT(R); QUALITY-OF-LIFE; GLOBUS-PALLIDUS AB Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery. (C) 2006 Movement Disorder Society. C1 Univ Kiel, Neurol Klin, D-24105 Kiel, Germany. Philadelphia VA Hosp, Dept Neurol, Philadelphia, PA USA. Cleveland Clin Fdn, Ctr Neurol Restorat, Cleveland, OH 44195 USA. Toronto Western Hosp, Dept Neurosurg, Toronto, ON M5T 2S8, Canada. Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. Univ Navarra, Dept Neurol & Neurosurg, Navarra, Spain. Osped San Paolo, Dept Neurol, Milan, Italy. Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Deuschl, G (reprint author), Univ Kiel, Neurol Klin, Niemannsweg 147, D-24105 Kiel, Germany. EM g.deuschl@neurologie.uni-kiel.de RI Deuschl, Gunther/A-7986-2010; OI Volkmann, Jens/0000-0002-9570-593X NR 165 TC 128 Z9 131 U1 1 U2 12 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. PY 2006 VL 21 SU 14 BP S219 EP S237 DI 10.1002/mds.20957 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA 057TR UT WOS:000238618600005 PM 16810719 ER PT J AU Lang, AE Houeto, JL Krack, P Kubu, C Lyons, KE Moro, E Ondo, W Pahwa, R Poewe, W Troster, AI Uitti, R Voon, V AF Lang, AE Houeto, JL Krack, P Kubu, C Lyons, KE Moro, E Ondo, W Pahwa, R Poewe, W Troster, AI Uitti, R Voon, V TI Deep brain stimulation: Preoperative issues SO MOVEMENT DISORDERS LA English DT Review DE deep brain stimulation; Parkinson's disease; predictive factors; indications; contraindications ID SUBTHALAMIC NUCLEUS STIMULATION; ADVANCED PARKINSONS-DISEASE; TERM-FOLLOW-UP; QUALITY-OF-LIFE; HIGH-FREQUENCY STIMULATION; MULTIPLE SYSTEM ATROPHY; BILATERAL PALLIDAL STIMULATION; CHRONIC ELECTRICAL-STIMULATION; GLOBUS-PALLIDUS; MOVEMENT-DISORDERS AB Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making. (C) 2006 Movement Disorder Society. C1 Toronto Western Hosp, Dept Neurol, Toronto, ON M5T 2S8, Canada. Univ Poitiers, Hosp La Miletrie, Dept Neurol, Poitiers, France. Univ Grenoble 1, Dept Neurol, Grenoble, France. Cleveland Clin Fdn, Ctr Neurol Restorat, Cleveland, OH 44195 USA. Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Univ Innsbruck Hosp, Dept Neurol, A-6020 Innsbruck, Austria. Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Lang, AE (reprint author), Toronto Western Hosp, Dept Neurol, 399 Bathurst St,7McL, Toronto, ON M5T 2S8, Canada. EM lang@uhnres.utoronto.ca NR 211 TC 117 Z9 120 U1 1 U2 4 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. PY 2006 VL 21 SU 14 BP S171 EP S196 DI 10.1002/mds.20955 PG 26 WC Clinical Neurology SC Neurosciences & Neurology GA 057TR UT WOS:000238618600003 PM 16810718 ER PT J AU Voon, V Kubu, C Krack, P Houeto, JL Troster, AI AF Voon, V Kubu, C Krack, P Houeto, JL Troster, AI TI Deep brain stimulation: Neuropsychological and neuropsychiatric issues SO MOVEMENT DISORDERS LA English DT Review DE Parkinson's disease; deep brain stimulation; depression; cognition; subthalamic ID SUBTHALAMIC NUCLEUS STIMULATION; ADVANCED PARKINSONS-DISEASE; BILATERAL PALLIDAL STIMULATION; OBSESSIVE-COMPULSIVE SYMPTOMS; PEDUNCULOPONTINE TEGMENTAL NUCLEUS; CHRONIC ELECTRICAL-STIMULATION; HIGH-FREQUENCY STIMULATION; QUALITY-OF-LIFE; BASAL GANGLIA; FOLLOW-UP AB Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well established. However, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. As a companion to the preoperative and postoperative sections of the DBS consensus articles, this article reviews the published literature on the cognitive and neuropsychiatric aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are transient, treatable, and potentially preventable. Outcome studies, methodological issues, pathophysiology, and preoperative and postoperative management of the cognitive and neuropsychiatric aspects and complications of DBS for PD are discussed. (C) 2006 Movement Disorder Society. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Cleveland Clin Fdn, Dept Psychiat & Psychol, Cleveland, OH 44195 USA. Univ Grenoble, Dept Neurol, Grenoble, France. Univ Grenoble, INSERM, U318, Grenoble, France. Univ Poitiers Hosp, Dept Neurol, Poitiers, France. Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC USA. RP Voon, V (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5S213,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov NR 154 TC 181 Z9 185 U1 0 U2 18 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. PY 2006 VL 21 SU 14 BP S305 EP S327 DI 10.1002/mds.20963 PG 23 WC Clinical Neurology SC Neurosciences & Neurology GA 057TR UT WOS:000238618600011 PM 16810676 ER PT S AU Efroni, S Harel, D Cohen, IR AF Efroni, Sol Harel, David Cohen, Irun R. BE Paton, R McNamara, LA TI A theory for complex systems: reactive animation SO MULTIDISCIPLINARY APPROACHES TO THEORY IN MEDICINE SE Studies in Multidisciplinarity LA English DT Article; Book Chapter ID SELF-NONSELF DISCRIMINATION; INTERFERON-GAMMA; AUTOIMMUNITY; STATECHARTS; DISEASES; MICE C1 [Efroni, Sol] NCI, Ctr Bioinformat, Rockville, MD USA. [Harel, David; Cohen, Irun R.] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. [Efroni, Sol; Harel, David] Weizmann Inst Sci, Dept Appl Math & Comp Sci, IL-76100 Rehovot, Israel. RP Efroni, S (reprint author), NCI, Ctr Bioinformat, Rockville, MD USA. NR 23 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 1571-0831 BN 978-0-08-045972-1 J9 STUD MULTIDISCIP PY 2006 VL 3 BP 309 EP 324 PG 16 WC Medicine, General & Internal; Multidisciplinary Sciences SC General & Internal Medicine; Science & Technology - Other Topics GA BCP89 UT WOS:000310981300018 ER PT S AU Crane, NJ Kansal, NS Dhanani, N Alemozaffar, M Kirk, AD Pinto, PA Elster, EA Huffman, SW Levin, IW AF Crane, Nicole J. Kansal, Neil S. Dhanani, Nadeem Alemozaffar, Mehrdad Kirk, Allan D. Pinto, Peter A. Elster, Eric A. Huffman, Scott W. Levin, Ira W. BE Azar, FS Metaxas, DM TI Visual enhancement of laparoscopic nephrectomies using the 3-CCD camera - art. no. 60810G SO Multimodal Biomedical Imaging SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Multimodal Biomedical Imaging CY JAN 21, 2003-JAN 24, 2006 CL San Jose, CA SP SPIE ID RENAL-FAILURE; CHEST-PAIN; TROPONIN-I; ISCHEMIA; REPERFUSION; KIDNEY; INJURY AB Many surgical techniques are currently shifting from the more conventional, open approach towards minimally invasive laparoscopic procedures. Laparoscopy results in smaller incisions, potentially leading to less postoperative pain and more rapid recoveries. One key disadvantage of laparoscopic surgery is the loss of three-dimensional assessment of organs and tissue perfusion. Advances in laparoscopic technology include high-definition monitors for improved visualization and upgraded single charge coupled device (CCD) detectors to 3-CCD cameras, to provide a larger, more sensitive color palette to increase the perception of detail. In this discussion, we further advance existing laparoscopic technology to create greater enhancement of images obtained during radical and partial nephrectomies in which the assessment of tissue perfusion is crucial but limited with current 3-CCD cameras. By separating the signals received by each CCD in the 3-CCD camera and by introducing a straight forward algorithm, rapid differentiation of renal vessels and perfusion is accomplished and could be performed real time. The newly acquired images are overlaid onto conventional images for reference and comparison. This affords the surgeon the ability to accurately detect changes in tissue oxygenation despite inherent limitations of the visible light image. Such additional capability should impact procedures in which visual assessment of organ vitality is critical. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Crane, NJ (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 NR 13 TC 0 Z9 0 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 0-8194-6123-7 J9 P SOC PHOTO-OPT INS PY 2006 VL 6081 BP G810 EP G810 AR 60810G DI 10.1117/12.663940 PG 8 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BEF86 UT WOS:000237152400013 ER PT J AU Liu, J Levens, D AF Liu, J Levens, D TI Making Myc SO MYC/MAX/MAD TRANSCRIPTION FACTOR NETWORK SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID HUMAN C-MYC; RNA-POLYMERASE-II; ZINC-FINGER PROTEIN; GENERAL TRANSCRIPTION FACTORS; PROMOTER-BINDING PROTEIN; SINGLE-STRANDED-DNA; NM23/NUCLEOSIDE DIPHOSPHATE KINASE; IMMUNOGLOBULIN-KAPPA-ENHANCERS; NUCLEAR RIBONUCLEOPROTEIN-K; 3.3 ANGSTROM RESOLUTION AB Myc regulates to some degree every major process in the cell. Proliferation, growth, differentiation, apoptosis, and metabolism are all under Myc control. In turn, these processes feed back to adjust the level of c-nyc expression. Although Myc is regulated at every level from RNA synthesis to protein degradation, c-myc transcription is particularly responsive to multiple diverse physiological and pathological signals. These signals are delivered to the c-myc promoter by a wide variety of transcription factors and chromatin remodeling complexes. How these diverse and sometimes disparate signals are processed to manage the Output of the c-myc promoter involves chromatin, recruitment of the transcription machinery, post-initiation transcriptional regulation, and mechanisms to provide dynamic feedback. Understanding these mechanisms promises to add new dimensions to models of transcriptional control and to reveal new strategies to manipulate Myc levels. C1 NCI, DCS, Gene Regulat Sect, Bethesda, MD 20892 USA. RP Levens, D (reprint author), NCI, DCS, Gene Regulat Sect, 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 181 TC 85 Z9 87 U1 1 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 302 BP 1 EP 32 PG 32 WC Immunology; Microbiology SC Immunology; Microbiology GA BEC53 UT WOS:000236799200001 PM 16620023 ER PT J AU Groll, AH Walsh, TJ AF Groll, Andreas H. Walsh, Thomas J. TI Antifungal efficacy and pharmacodynamics of posaconazole in experimental models of invasive fungal infections SO MYCOSES LA English DT Article DE posaconazole; triazoles; antifungal agents; mycoses; aspergillosis; candidiasis; animal models; pharmacokinetics; pharmacodynamics ID IN-VIVO ACTIVITIES; TRYPANOSOMA SCHIZOTRYPANUM CRUZI; COLONY-STIMULATING FACTOR; SCH 56592 POSACONAZOLE; AMPHOTERICIN-B; MURINE MODEL; CEREBRAL PHEOHYPHOMYCOSIS; PULMONARY ASPERGILLOSIS; RAMICHLORIDIUM-MACKENZIEI; CRYPTOCOCCUS-NEOFORMANS AB Posaconazole is a novel lipophilic antifungal triazole with potent and broad-spectrum activity against opportunistic, endemic and dermatophytic fungi. This activity extends to organisms that are often refractory to existing triazoles, amphotericin B or echinocandins such as Candida glabrata, Candida krusei, Aspergillus terreus, Fusarium spp. and the Zygomycetes. A large number of experimental animal models of invasive fungal infections has demonstrated the potent and broad-spectrum efficacy of posaconazole in vivo, both in normal and in immunocompromised animals. Consistent with these preclinical data, posaconazole showed strong a antifungal efficacy in phase II and phase III clinical trials in immunocompromised patients with oropharyngeal and oesophageal candidiasis and as salvage therapy in patients with invasive fungal infections, and was effective as antifungal prophylaxis in high-risk patients. This paper reviews the preclinical disposition, antifungal efficacy and pharmacodynamics of posaconazole in and its implications for treatment and prevention of invasive fungal infections. C1 Childrens Univ Hosp, Infect Dis Res Program, Dept Pediat Hematol & Oncol, D-48149 Munster, Germany. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD USA. RP Groll, AH (reprint author), Childrens Univ Hosp, Infect Dis Res Program, Dept Hematol Oncol, Albert Schweitzer Str 33, D-48149 Munster, Germany. EM grollan@ukmuenster.de NR 48 TC 20 Z9 22 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0933-7407 J9 MYCOSES JI Mycoses PY 2006 VL 49 SU 1 BP 7 EP 16 DI 10.1111/j.1439-0507.2006.01296.x PG 10 WC Dermatology; Mycology SC Dermatology; Mycology GA 082RJ UT WOS:000240404600003 PM 16961576 ER PT S AU Namboodiri, AMA Moffett, JR Arun, P Mathew, R Namboodiri, S Potti, A Hershfield, J Kirmani, B Jacobowitz, DM Madhavarao, CN AF Namboodiri, AMA Moffett, JR Arun, P Mathew, R Namboodiri, S Potti, A Hershfield, J Kirmani, B Jacobowitz, DM Madhavarao, CN BE Moffett, JR Tieman, SB Weinberger, DR Coyle, JT Namboodiri, AMA TI Defective myelin lipid synthesis as a pathogenic mechanism of Canavan disease SO N-ACETYLASPARTATE: A UNIQUE NEURONAL MOLECULE IN THE CENTRAL NERVOUS SYSTEM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on N-Acetylaspartate CY SEP 13-14, 2004 CL Bethesda, MD SP Natl Inst Mental Hlth, Natl Inst Neurol Disorder & Stroke, Natl Inst Child Hlth & Human Dev, Natl Inst Hlth, Off Rare Dis ID CENTRAL-NERVOUS-SYSTEM; N-ACETYLASPARTATE IMMUNOREACTIVITIES; FATTY ACID SYNTHESIS; ACETYL-L-ASPARTATE; RAT-BRAIN; SPONGY DEGENERATION; IMMUNOHISTOCHEMICAL LOCALIZATION; ASPARTOACYLASE DEFICIENCY; DIFFERENTIAL DISTRIBUTION; TRITIATED-WATER C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Madhavarao, CN (reprint author), Uniformed Serv Univ Hlth Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NINDS NIH HHS [R01 NS39387] NR 52 TC 12 Z9 12 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-387-30171-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 576 BP 145 EP 163 PG 19 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Clinical Neurology; Neurosciences SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BED79 UT WOS:000236895900010 PM 16802710 ER PT S AU Marenco, S Bertolino, A Weinberger, DR AF Marenco, S Bertolino, A Weinberger, DR BE Moffett, JR Tieman, SB Weinberger, DR Coyle, JT Namboodiri, AMA TI In vivo NMR measures of NAA and the neurobiology of schizophrenia SO N-ACETYLASPARTATE: A UNIQUE NEURONAL MOLECULE IN THE CENTRAL NERVOUS SYSTEM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on N-Acetylaspartate CY SEP 13-14, 2004 CL Bethesda, MD SP Natl Inst Mental Hlth, Natl Inst Neurol Disorder & Stroke, Natl Inst Child Hlth & Human Dev, Natl Inst Hlth, Off Rare Dis ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYLASPARTATE MEASURES; STRIATAL DOPAMINE; METHODOLOGICAL ISSUES; HIPPOCAMPAL DAMAGE; PREFRONTAL NEURONS; ACETYL ASPARTATE; CORTEX; PATHOLOGY; PATTERN C1 NIMH, Genes Cognit & Psychosis Program, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), 10 Ctr Dr,Rm 4S-235, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 29 TC 10 Z9 10 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-387-30171-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 576 BP 227 EP 240 PG 14 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Clinical Neurology; Neurosciences SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Neurosciences & Neurology GA BED79 UT WOS:000236895900016 PM 16802716 ER PT S AU Zhang, TQ Danthi, SN Xie, JW Hu, DH Lu, P Li, K AF Zhang, Tieqiao Danthi, S. Narasimhan Xie, Jianwu Hu, Dehong Lu, Peter Li, King BE Cartwright, AN Nicolau, DV TI Live cell imaging of the endocytosis and the intracellular trafficking of multifunctional lipid nanoparticles - art. no. 60950D SO Nanobiophotonics and Biomedical Applications III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Nanobiophotonics and Biomedical Applications III CY JAN 23-24, 2006 CL San Jose, CA SP SPIE DE cell imaging; microscopy; particle tracking; lipid nanoparticle; endocytosis; M21 AB Artificial lipid naroparticles have drawn great attention due to their potential in medicine. Linked with targeting ligands, they can be used as probes and/or gene delivery vectors for specific types of target cells. Therefore, they are very promising agents in early detection, diagnosis and treatment of cancers and other genetic diseases. However, there are several barriers blocking the applications. Controlling the cellular uptake of the lipid nanoparticles is an important technical challenge to overcome. Understanding the mechanism of the endocytosis and the following intracellular trafficking is very important for improving the design and therefore the efficiency as a drug delivery system. By using fluorescence microscopy methods, we studied the endocytosis of lipid nanoparticles by live M21 cells. The movements of the nanoparticles inside the cell were quantitatively characterized and classified based on the diffusion behavior. The trajectories of nanoparticles movement over the cell membrane revealed hop-diffusion behavior prior to the endocytosis. Fast movement in large steps is observed in intracellular trafficking and is attributed to active movement along microtubule. These observations help to understand the mechanism of the endocytosis and the pathway of the particles in cells. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Zhang, TQ (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 3 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 0-8194-6137-7 J9 P SOC PHOTO-OPT INS PY 2006 VL 6095 BP D950 EP D950 AR 60950D DI 10.1117/12.645398 PG 4 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Optics SC Engineering; Science & Technology - Other Topics; Optics GA BEL17 UT WOS:000237699500008 ER PT J AU Stoeckert, C Ball, C Brazma, A Brinkman, R Causton, H Fan, LJ Fostel, J Fragoso, G Heiskanen, M Holstege, F Morrison, N Parkinson, H Quackenbush, J Rocca-Serra, P Sansone, SA Sarkans, U Sherlock, G Stevens, R Taylor, C Taylor, R Whetzel, P White, J AF Stoeckert, C Ball, C Brazma, A Brinkman, R Causton, H Fan, LJ Fostel, J Fragoso, G Heiskanen, M Holstege, F Morrison, N Parkinson, H Quackenbush, J Rocca-Serra, P Sansone, SA Sarkans, U Sherlock, G Stevens, R Taylor, C Taylor, R Whetzel, P White, J TI To the editor SO NATURE BIOTECHNOLOGY LA English DT Letter C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. European Bioinformat Inst, EMBL Outstn, Cambridge CB101SD, England. British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. Univ London Imperial Coll Sci Technol & Med, CSC IC Microarray Ctr, London W12 0NN, England. KEVRIC, Silver Spring, MD 20910 USA. IMC Co, Silver Spring, MD 20910 USA. Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Natl Inst Gen Med Sci, Ctr Bioinformat & Computat Biol, Bethesda, MD 20892 USA. Univ Utrecht, Med Ctr, Genom Lab, NL-3584 CG Utrecht, Netherlands. Univ Manchester, Sch Comp Sci, Manchester M13 9PL, Lancs, England. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Pacific NW Natl Lab, Computat BioSci Grp, Div Biol Sci, Richland, WA 99352 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Stoeckert, C (reprint author), Univ Penn, Sch Med, 1415 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM stoeckrt@pcbi.upenn.edu RI Sherlock, Gavin/B-1831-2009; Sherlock, Gavin/E-9110-2012; Brinkman, Ryan/B-1108-2008 OI Brinkman, Ryan/0000-0002-9765-2990 NR 0 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2006 VL 24 IS 1 BP 21 EP 22 DI 10.1038/nbt0106-21b PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 001SE UT WOS:000234555800011 PM 16404382 ER PT J AU Samakoglu, S Lisowski, L Budak-Alpdogan, T Usachenko, Y Acuto, S Di Marzo, R Maggio, A Zhu, P Tisdale, JF Riviere, I Sadelain, M AF Samakoglu, S Lisowski, L Budak-Alpdogan, T Usachenko, Y Acuto, S Di Marzo, R Maggio, A Zhu, P Tisdale, JF Riviere, I Sadelain, M TI A genetic strategy to treat sickle cell anemia by coregulating globin transgene expression and RNA interference SO NATURE BIOTECHNOLOGY LA English DT Article ID HUMAN BETA-GLOBIN; CORD BLOOD-CELLS; MESSENGER-RNAS; MOUSE MODELS; DISEASE; THERAPY; MICE; ACTIVATION AB The application of RNA interference (RNAi) to stem cell-based gene therapies will require highly specific and lineage-restricted gene silencing. Here we show the feasibility and therapeutic potential of coregulating transgene expression and RNAi in hematopoietic stem cells. We encoded promoterless small-hairpin RNA (shRNA) within the intron of a recombinant c-globin gene. Expression of both c-globin and the lariat-embedded small interfering RNA (siRNA) was induced upon erythroid differentiation, specifically downregulating the targeted gene in tissue- and differentiation stage-specific fashion. The position of the shRNA within the intron was critical to concurrently achieve high-level transgene expression, effective siRNA generation and minimal interferon induction. Lentiviral transduction of CD34(+) cells from patients with sickle cell anemia led to erythroid-specific expression of the gamma-globin transgene and concomitant reduction of endogenous beta(S) transcripts, thus providing proof of principle for therapeutic strategies that require synergistic gene addition and gene silencing in stem cell progeny. C1 Sloan Kettering Inst, Lab Gene Transfer & Gene Express, New York, NY 10021 USA. Sloan Kettering Inst, Gene Transfer & Somat Cell Engn Facil, New York, NY 10021 USA. Univ Med & Dent New Jersey, Dept Med, New Brunswick, NJ 08901 USA. Osped V Cervello, Div Ematol Tallassemia 2, I-90146 Palermo, Italy. NIDDK, MCHB, DHHS, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. RP Sadelain, M (reprint author), Sloan Kettering Inst, Lab Gene Transfer & Gene Express, New York, NY 10021 USA. EM m-sadelain@ski.mskcc.org RI Acuto, Santina/K-7582-2016; Maggio, Aurelio/K-7812-2016 OI Acuto, Santina/0000-0001-7749-2259; Maggio, Aurelio/0000-0002-9601-900X FU NCI NIH HHS [CA08748, CA59350]; NHLBI NIH HHS [HL57612] NR 30 TC 74 Z9 80 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2006 VL 24 IS 1 BP 89 EP 94 DI 10.1038/nbt1176 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 001SE UT WOS:000234555800029 PM 16378095 ER PT J AU Lee, HS Bong, YS Moore, KB Soria, K Moody, SA Daar, IO AF Lee, HS Bong, YS Moore, KB Soria, K Moody, SA Daar, IO TI Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway SO NATURE CELL BIOLOGY LA English DT Article ID XENOPUS GASTRULATION; FORMATION REQUIRE; RETINAL FATE; RECEPTOR; GENE; MORPHOGENESIS; MOVEMENTS; PROGENITORS; ACTIVATION; EXPRESSION AB An important step in retinal development is the positioning of progenitors within the eye field where they receive the local environmental signals that will direct their ultimate fate(1). Recent evidence indicates that ephrinB1 functions in retinal progenitor movement, but the signalling pathway is unclear. We present evidence that ephrinB1 signals through its intracellular domain to control retinal progenitor movement into the eye field by interacting with Xenopus Dishevelled ( Xdsh), and by using the planar cell polarity ( PCP) pathway. Blocking Xdsh translation prevents retinal progeny from entering the eye field, similarly to the morpholino- mediated loss of ephrinB1 ( ref. 2). Overexpression of Xdsh can rescue the phenotype induced by loss of ephrinB1, and this rescue ( as well as a physical association between Xdsh and ephrinB1) is completely dependent on the DEP ( Dishevelled, Egl- 10, Pleckstrin) domain of Xdsh. Similar gain- and loss- of- function experiments suggest that Xdsh associates with ephrinB1 and mediates ephrinB1 signalling through downstream members of the PCP pathway during eye field formation. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Univ Utah, Sch Med, Dept Neurobiol & Anat, Salt Lake City, UT 84132 USA. George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. RP Daar, IO (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM daar@ncifcrf.gov RI Lee, Hyun-Shik/G-3555-2011; OI Daar, Ira/0000-0003-2657-526X; Moody, Sally/0000-0003-4192-1087 FU Intramural NIH HHS; NEI NIH HHS [EY10096] NR 34 TC 76 Z9 79 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JAN PY 2006 VL 8 IS 1 BP 55 EP U21 DI 10.1038/ncb1344 PG 14 WC Cell Biology SC Cell Biology GA 002ZN UT WOS:000234651500012 PM 16362052 ER PT J AU Nieman, LK AF Nieman, LK TI Difficulty in the diagnosis of Cushing disease SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Article DE adrenocorticotropic hormone; cortisol; Cushing disease; Cushing syndrome; inferior-petrosal-sinus sampling ID CORTICOTROPIN-RELEASING HORMONE; DIFFERENTIAL-DIAGNOSIS; STATES; CORTISOL AB Background A 48-year-old woman presented to our clinic I year after hypertension was discovered on a routine screening visit. During the previous year, she had noticed weight gain in the face and abdomen, easy bruising, oligomenorrhea and facial and periareolar hair growth. On presentation, she reported no weakness, fracture, back pain, depression, irritability, problem with cognition or memory, increased appetite, hot flashes or altered sleep. Previous medication history included 2.5 mg lisinopril daily and 25.0 mg hydrochlorothiazide daily for 12 months. Investigations Measurement of urine glucocorticoid excretion, evening plasma and salivary cortisol levels, and basal and corticotropin-releasing-hormone-stimulated adrenocorticotropic hormone and cortisol levels. An overnight 8 mg dexamethasone suppression test, pituitary MRI, inferior-petrosal-sinus sampling, cavernous sinus and jugular venous sampling were performed. Diagnosis Cushing disease. Management The patient underwent trans-sphenoidal resection, assessment of remission and subsequent treatment with hydrocortisone. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), CRC, Bldg 10,1 E,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM niemanl@nih.gov FU Intramural NIH HHS NR 15 TC 6 Z9 7 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD JAN PY 2006 VL 2 IS 1 BP 53 EP 57 DI 10.1038/ncpendmet.0074 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 010DC UT WOS:000235166100006 PM 16932253 ER PT J AU Simon, R AF Simon, R TI Targets for treatment success SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material C1 NCI, Biometr Res Branch, Rockville, MD USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Rockville, MD USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JAN PY 2006 VL 3 IS 1 BP 1 EP 1 DI 10.1038/ncponc0402 PG 1 WC Oncology SC Oncology GA 998OE UT WOS:000234327600001 PM 16407857 ER PT J AU Choong, NW Dietrich, S Seiwert, TY Tretiakova, MS Nallasura, V Davies, GC Lipkowitz, S Husain, AN Salgia, R Ma, PC AF Choong, NW Dietrich, S Seiwert, TY Tretiakova, MS Nallasura, V Davies, GC Lipkowitz, S Husain, AN Salgia, R Ma, PC TI Gefitinib response of erlotinib-refractory lung cancer involving meninges - role of EGFR mutation SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Article DE epidermal growth factor receptor; leptomeningeal carcinomatosis; lung cancer; mutation; small-molecule inhibitor ID BRAIN METASTASES; RECEPTOR GENE; RESPONSIVENESS; RESISTANCE; TRIAL AB Background A 70-year-old Japanese-American woman who had never smoked was diagnosed with stage IV non-small-cell lung cancer with rib metastases. She had previously been well and she had no family history of malignancy. While receiving treatment with erlotinib, an epidermal growth factor receptor small-molecule inhibitor, she progressed and developed new brain metastases. She failed further chemotherapy treatments and subsequently developed extensive symptomatic leptomeningeal carcinomatosis associated with diplopia, hemiparesis, weightloss, and incontinence. Investigations Chest X-ray, head and chest CT scan, R2 lymph-node biopsy, histopathology, immunohistochemistry, MRI of head and spine, lumbar puncture, laser microdissection and EGFR genomic DNA sequencing of the R2 lymph node and cerebrospinal fluid tumor cells. Diagnosis Erlotinib-refractory stage IV lung adenocarcinoma and end-stage symptomatic leptomeningeal metastases with a novel double L858R+E884K somatic mutation of the EGFR. Management Carboplatin, paclitaxel and erlotinib, whole-brain radiotherapy, temozolomide with and without irinotecan, and gefitinib. C1 Case Comprehens Canc Ctr, Ireland Canc Ctr, Cleveland, OH 44106 USA. Univ Chicago, Pritzker Sch Med, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Aerodigest Tract Translat Res Labs, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Thorac Oncol Res Program, Chicago, IL 60637 USA. Univ Jena, D-6900 Jena, Germany. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Case Western Reserve Univ, Thorac Oncol Program, Cleveland, OH 44106 USA. RP Ma, PC (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Case Sch Med, Div Hematol Oncol, Wolstein Res Bldg WRB 2-123,10900 Euclid Ave, Cleveland, OH 44106 USA. EM patrick.ma@case.edu RI Nallasura, Vidya/D-8947-2011; Dietrich, Sascha/J-2562-2015 OI Dietrich, Sascha/0000-0002-0648-1832 FU Intramural NIH HHS NR 16 TC 84 Z9 90 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JAN PY 2006 VL 3 IS 1 BP 50 EP 57 DI 10.1038/ncponc0400 PG 8 WC Oncology SC Oncology GA 998OE UT WOS:000234327600012 PM 16407879 ER PT J AU Singh, NJ Schwartz, RH AF Singh, NJ Schwartz, RH TI Primer: mechanisms of immunologic tolerance SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Review DE anergy; autoimmunity; self-reactivity; tolerance; tuning ID REGULATORY T-CELLS; AUTOIMMUNE-DISEASE; B-CELLS; ADAPTIVE TOLERANCE; SELF-TOLERANCE; RECEPTORS; SELECTION; IMMUNITY; POLYENDOCRINOPATHY; HOMEOSTASIS AB Successful adaptive immunity against a broad range of pathogens depends on the diversity of randomly generated T-lymphocyte and B-lymphocyte receptors. A subset of these receptors will be self-reactive and must be regulated to prevent autoimmunity. The process of immunologic tolerance addresses this problem by either purging autoreactive receptors from the system or tuning down their reactivity sufficiently to prevent disease. Immature lymphocytes generate a novel receptor during development in the thymus or bone marrow. Engagement of self antigens by these nascent receptors leads to their purging, either by the apoptotic death of the lymphocyte or by the initiation of receptor editing, a process in which the autoreactive receptor is replaced. If the lymphocytes mature further, the activation threshold of autoreactive cells can be tuned by the co-expression of inhibitory receptors or negative signaling molecules, allowing the persistence of the receptor without an increased risk of autoimmunity. T-cell and B-cell receptors that escape these checkpoints can still be regulated in the peripheral immune system by both purging and tuning mechanisms. A separate set of mechanisms, mediated by various regulatory cells, also operates to tune peripheral receptors in a cell-extrinsic fashion. The combined action of these processes ensures that the organism does not suffer autoimmune pathology, even if autoreactive receptors are generated and maintained in the immune system. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Rm 111,MSC-0420, Bethesda, MD 20892 USA. EM rs34r@niaid.nih.gov FU Intramural NIH HHS NR 40 TC 26 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD JAN PY 2006 VL 2 IS 1 BP 44 EP 52 DI 10.1038/ncprheum0049 PG 9 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 010CW UT WOS:000235165500006 PM 16932651 ER PT J AU Ioannidis, JPA Gwinn, M Little, J Higgins, JPT Bernstein, JL Boffetta, P Bondy, M Bray, MS Brenchley, PE Buffler, PA Casas, JP Chokkalingam, A Danesh, J Smith, GD Dolan, S Duncan, R Gruis, NA Hartge, P Hashibe, M Hunter, DJ Jarvelin, MR Malmer, B Maraganore, DM Newton-Bishop, JA O'Brien, TR Petersen, G Riboli, E Salanti, G Seminara, D Smeeth, L Taioli, E Timpson, N Uitterlinden, AG Vineis, P Wareham, N Winn, DM Zimmern, R Khoury, MJ AF Ioannidis, JPA Gwinn, M Little, J Higgins, JPT Bernstein, JL Boffetta, P Bondy, M Bray, MS Brenchley, PE Buffler, PA Casas, JP Chokkalingam, A Danesh, J Smith, GD Dolan, S Duncan, R Gruis, NA Hartge, P Hashibe, M Hunter, DJ Jarvelin, MR Malmer, B Maraganore, DM Newton-Bishop, JA O'Brien, TR Petersen, G Riboli, E Salanti, G Seminara, D Smeeth, L Taioli, E Timpson, N Uitterlinden, AG Vineis, P Wareham, N Winn, DM Zimmern, R Khoury, MJ CA Human Genome Epidemiology Network Network Investigtor Networks TI A road map for efficient and reliable human genome epidemiology SO NATURE GENETICS LA English DT Editorial Material ID GENETIC EPIDEMIOLOGY; RANDOMIZED-TRIALS; PUBLICATION; ASSOCIATION; GUIDELINES; BIAS; ENVIRONMENT; FALSE AB Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews. C1 Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. Fdn Res & Technol Hellas, Biomed Res Inst, GR-45110 Ioannina, Greece. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. Ctr Dis Control & Prevent, Off Genom & Dis Prevent, Atlanta, GA 30333 USA. Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON K1H 8M5, Canada. Univ Cambridge, MRC, Biostat Unit, Cambridge CB2 2SR, England. Strangeways Res Lab, Publ Hlth Genet Unit, Cambridge CB1 8RN, England. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Int Agcy Res Canc, F-69008 Lyon, France. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Royal Infirm, Manchester Inst Nephrol & Transplantat, Renal Res Labs, Manchester M13 9WL, Lancs, England. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ London London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1E 7HT, England. Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England. March Dimes, White Plains, NY 10605 USA. WHO, CH-1211 Geneva, Switzerland. Leiden Univ Med Ctr, Dept Dermatol, NL-2333 AL Leiden, Netherlands. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ London Imperial Coll Sci & Technol, Dept Epidemiol & Publ Hlth, London W2 1PG, England. Univ Oulu, Dept Publ Hlth Sci & Gen Practice, Oulu, Finland. Umea Univ Hosp, Dept Radiat Sci, Umea, Sweden. Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. CR UK Clin Ctr, Genet Epidemiol Div, Leeds LS8 7FT, W Yorkshire, England. Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15232 USA. Erasmus MC, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands. Erasmus MC, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Inst Sci Interchange Fdn, Turin, Italy. MRC, Epidemiol Unit, Elsie Widdowson Labs, Cambridge CB1 9NL, England. RP Ioannidis, JPA (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. EM jioannid@cc.uoi.gr RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Fox, Laura /C-6249-2016; OI Higgins, Julian/0000-0002-8323-2514; Gruis, Nelleke/0000-0002-5210-9150; Monsalve, Beatriz Elena/0000-0002-5994-866X; Brenchley, Paul/0000-0003-1290-9919; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Newton Bishop, Julia/0000-0001-9147-6802; Timpson, Nicholas/0000-0002-7141-9189; Davey Smith, George/0000-0002-1407-8314 FU Medical Research Council [MC_U106179471, G108/492] NR 24 TC 157 Z9 161 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2006 VL 38 IS 1 BP 3 EP 5 DI 10.1038/ng0106-3 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 997EG UT WOS:000234227200002 PM 16468121 ER PT J AU Hardy, J AF Hardy, J TI Amyloid double trouble SO NATURE GENETICS LA English DT Editorial Material ID PRECURSOR PROTEIN GENE; ALZHEIMERS-DISEASE; CEREBRAL-HEMORRHAGE; DOWNS-SYNDROME; DEMENTIA; MUTATION; HYPOTHESIS; LOCUS AB A new study shows that some cases of early-onset Alzheimer disease result from duplications of the APP locus, which encodes the amyloid beta precursor protein. This finding fulfills a 20-year-old prediction that genetic variability in APP expression could lead to disease and provides further, perhaps definitive, evidence for the amyloid hypothesis of the disorder. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 15 TC 23 Z9 23 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2006 VL 38 IS 1 BP 11 EP 12 DI 10.1038/ng0106-11 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 997EG UT WOS:000234227200004 PM 16380721 ER PT J AU Helgadottir, A Manolescu, A Helgason, A Thorleifsson, G Thorsteinsdottir, U Gudbjartsson, DF Gretarsdottir, S Magnusson, KP Gudmundsson, G Hicks, A Jonsson, T Grant, SFA Sainz, J O'Brien, SJ Sveinbjornsdottir, S Valdimarsson, EM Matthiasson, SE Levey, AI Abramson, JL Reilly, MP Vaccarino, V Wolfe, ML Gudnason, V Quyyumi, AA Topol, EJ Rader, DJ Thorgeirsson, G Gulcher, JR Hakonarson, H Kong, A Stefansson, K AF Helgadottir, A Manolescu, A Helgason, A Thorleifsson, G Thorsteinsdottir, U Gudbjartsson, DF Gretarsdottir, S Magnusson, KP Gudmundsson, G Hicks, A Jonsson, T Grant, SFA Sainz, J O'Brien, SJ Sveinbjornsdottir, S Valdimarsson, EM Matthiasson, SE Levey, AI Abramson, JL Reilly, MP Vaccarino, V Wolfe, ML Gudnason, V Quyyumi, AA Topol, EJ Rader, DJ Thorgeirsson, G Gulcher, JR Hakonarson, H Kong, A Stefansson, K TI A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction SO NATURE GENETICS LA English DT Article ID MULTILOCUS GENOTYPE DATA; POPULATION-STRUCTURE; ADMIXED POPULATIONS; ADMIXTURE; DISEASE; 5-LIPOXYGENASE; RACE; MYELOPEROXIDASE; ASSOCIATIONS; INFERENCE AB Variants of the gene ALOX5AP ( also known as FLAP) encoding arachidonate 5-lipoxygenase activating protein are known to be associated with risk of myocardial infarction(1). Here we show that a haplotype (HapK) spanning the LTA4H gene encoding leukotriene A4 hydrolase, a protein in the same biochemical pathway as ALOX5AP, confers modest risk of myocardial infarction in an Icelandic cohort. Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway. Three cohorts from the United States also show that HapK confers a modest relative risk (1.16) in European Americans, but it confers a threefold larger risk in African Americans. About 27% of the European American controls carried at least one copy of HapK, as compared with only 6% of African American controls. Our analyses indicate that HapK is very rare in Africa and that its occurrence in African Americans is due to European admixture. Interactions with other genetic or environmental risk factors that are more common in African Americans are likely to account for the greater relative risk conferred by HapK in this group. C1 deCODE Genet Inc, IS-101 Reykjavik, Iceland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Natl Univ Hosp Reykjavik, Reykjavik, Iceland. Emory Univ, Sch Med, Atlanta, GA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Iceland Heart Assoc, Reykjavik, Iceland. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Stefansson, K (reprint author), deCODE Genet Inc, Sturlugata 8, IS-101 Reykjavik, Iceland. EM kstefans@decode.is RI Magnusson, Kristinn/A-6479-2011; Manolescu, Andrei /G-4565-2014; Helgason, Agnar/K-1522-2015; Gudnason, Vilmundur/K-6885-2015; Hicks, Andrew/E-9518-2017; OI Magnusson, Kristinn/0000-0003-4528-6826; Manolescu, Andrei /0000-0002-0713-4664; Gudnason, Vilmundur/0000-0001-5696-0084; Hicks, Andrew/0000-0001-6320-0411; Gudbjartsson, Daniel/0000-0002-5222-9857; Topol, Eric/0000-0002-1478-4729 FU NCRR NIH HHS [M01-RR00039]; NHLBI NIH HHS [P50 HL077107-01]; NIEHS NIH HHS [U54 ES012068] NR 30 TC 239 Z9 248 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2006 VL 38 IS 1 BP 68 EP 74 DI 10.1038/ng1692 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 997EG UT WOS:000234227200019 PM 16282974 ER PT J AU Koff, WC Johnson, PR Watkins, DI Burton, DR Lifson, JD Hasenkrug, KJ McDermott, AB Schultz, A Zamb, TJ Boyle, R Desrosiers, RC AF Koff, WC Johnson, PR Watkins, DI Burton, DR Lifson, JD Hasenkrug, KJ McDermott, AB Schultz, A Zamb, TJ Boyle, R Desrosiers, RC TI HIV vaccine design: insights from live attenuated SIV vaccines SO NATURE IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; MUCOSAL IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; LONG-TERM CONTROL; RHESUS MACAQUES; VIRAL REPLICATION; VAGINAL CHALLENGE; SIVMAC251 CHALLENGE; EFFECTIVE INDUCTION; CELL RESPONSES AB The International AIDS Vaccine Initiative has established a consortium to elucidate mechanisms of protection conferred by live attenuated simian immunodeficiency virus vaccines in monkeys. Here, the strategies defining key components of the protective immune response elicited by these vaccines are discussed. C1 Int AIDS Vaccine Initiat, New York, NY 10038 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Wisconsin, Wisconsin Primate Res Ctr, Madison, WI 53706 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. NCI, Sci Applicat Int Corp, AID Vaccine Program, Retroviral Pathogenesis Lab, Ft Detrick, MD 21702 USA. NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. RP Koff, WC (reprint author), Int AIDS Vaccine Initiat, New York, NY 10038 USA. EM wkoff@iavi.org RI Johnson, Philip/A-6892-2009 FU NCI NIH HHS [N01-CO-12400] NR 46 TC 185 Z9 188 U1 3 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2006 VL 7 IS 1 BP 19 EP 23 DI 10.1038/ni1296 PG 5 WC Immunology SC Immunology GA 995XZ UT WOS:000234139700014 PM 16357854 ER PT J AU Spiegel, AM Nabel, EG AF Spiegel, AM Nabel, EG TI NIH research on obesity and type 2 diabetes: providing the scientific evidence base for actions to improve health SO NATURE MEDICINE LA English DT Editorial Material C1 NIDDK, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDK, NIH, Bldg 31,Room 9A52,31 Ctr Dr,MSC 2560, Bethesda, MD 20892 USA. EM spiegela@extra.niddk.nih.gov NR 0 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2006 VL 12 IS 1 BP 67 EP 69 DI 10.1038/nm0106-67 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 999VO UT WOS:000234419000052 PM 16397572 ER PT J AU Fichtner-Feigl, S Strober, W Kawakami, K Puri, RK Kitani, A AF Fichtner-Feigl, S Strober, W Kawakami, K Puri, RK Kitani, A TI IL-13 signaling through the IL-13 alpha 2 receptor is involved in induction of TGF-beta 1 production and fibrosis SO NATURE MEDICINE LA English DT Article ID GROWTH FACTOR-BETA-1 GENE; NK-T-CELLS; PULMONARY-FIBROSIS; ULCERATIVE-COLITIS; OXAZOLONE COLITIS; TISSUE FIBROSIS; ALPHA-2 CHAIN; IN-VIVO; MICE; INTERLEUKIN-13 AB Interleukin (IL)-13 is a major inducer of fibrosis in many chronic infectious and autoimmune diseases. In studies of the mechanisms underlying such induction, we found that IL-13 induces transforming growth factor (TGF)-beta(1) in macrophages through a two-stage process involving, first, the induction of a receptor formerly considered to function only as a decoy receptor, IL-13R alpha(2). Such induction requires IL-13 (or IL-4) and tumor necrosis factor (TNF)-alpha. Second, it involves IL-13 signaling through IL-13R alpha(2) to activate an AP-1 variant containing c-jun and Fra-2, which then activates the TGFB1 promoter. In vivo, we found that prevention of IL-13R alpha(2) expression reduced production of TGF-beta(1) in oxazolone-induced colitis and that prevention of IL-13Ra2 expression, Il13ra2 gene silencing or blockade of IL-13R alpha(2) signaling led to marked downregulation of TGF-beta(1) production and collagen deposition in bleomycin-induced lung fibrosis. These data suggest that IL-13R alpha(2) signaling during prolonged inflammation is an important therapeutic target for the prevention of TGF-beta(1)-mediated fibrosis. C1 NIAID, NIH, Mucosal Immun Sect, Lab Host Def, Bethesda, MD 20892 USA. Univ Regensburg, Dept Surg, Med Ctr, D-93053 Regensburg, Germany. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, NIH, Mucosal Immun Sect, Lab Host Def, Bldg 10-CRC 5W3864,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov FU Intramural NIH HHS NR 44 TC 426 Z9 457 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2006 VL 12 IS 1 BP 99 EP 106 DI 10.1038/nm1332 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 999VO UT WOS:000234419000058 PM 16327802 ER PT J AU Aragona, BJ Liu, Y Yu, YJ Curtis, JT Detwiler, JM Insel, TR Wang, ZX AF Aragona, BJ Liu, Y Yu, YJ Curtis, JT Detwiler, JM Insel, TR Wang, ZX TI Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds SO NATURE NEUROSCIENCE LA English DT Article ID FEMALE PRAIRIE VOLES; COCAINE-SEEKING BEHAVIOR; MICROTUS-OCHROGASTER; PARTNER PREFERENCES; SOCIAL-ORGANIZATION; MOLECULAR-MECHANISMS; DRUG-ADDICTION; D-2 RECEPTORS; MALE-RATS; VASOPRESSIN AB The involvement of dopamine within the nucleus accumbens in the formation and maintenance of pair bonds was assessed in a series of experiments using the monogamous prairie vole. We show that dopamine transmission that promotes pair bond formation occurs within the rostral shell of the nucleus accumbens, but not in its core or caudal shell. Within this specific brain region, D1- and D2-like receptor activation produced opposite effects: D1-like activation prevented pair bond formation, whereas D2-like activation facilitated it. After extended cohabitation with a female, male voles showed behavior indicative of pair bond maintenance-namely, selective aggression towards unfamiliar females. These voles also showed a significant upregulation in nucleus accumbens D1- like receptors, and blockade of these receptors abolished selective aggression. Thus, neuroplastic reorganization of the nucleus accumbens dopamine system is responsible for the enduring nature of monogamous pair bonding. Finally, we show that this system may also contribute to species-specific social organization. C1 Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. NIMH, Bethesda, MD 20892 USA. RP Aragona, BJ (reprint author), Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA. EM aragona@unc.edu FU NICHD NIH HHS [HD-40722]; NIDA NIH HHS [DA-19627]; NIMH NIH HHS [MH-67396, MH-58616, MH-66734] NR 50 TC 203 Z9 211 U1 3 U2 41 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2006 VL 9 IS 1 BP 133 EP 139 DI 10.1038/nn1613 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 997ZQ UT WOS:000234288000027 PM 16327783 ER PT J AU Chattopadhyay, PK Yu, J Roederer, M AF Chattopadhyay, Pratip K. Yu, Joanne Roederer, Mario TI Live-cell assay to detect antigen-specific CD4(+) T-cell responses by CD154 expression SO NATURE PROTOCOLS LA English DT Article ID CD40 LIGAND; HIV-INFECTION; ACTIVATION; INDUCTION AB This protocol details a method to identify CD4+ T cells that respond to antigens. The method relies on detection of CD154, a costimulatory cell surface protein that is expressed by CD4+ T cells upon activation, and can be used to purify live CD4+ T cells of diverse function. To detect CD154, fluorescently labeled antibodies are cultured with cell samples, peptides ( or whole antigens) and monensin during a 6- to 24-h stimulation period. ( Note that the assay is not compatible with brefeldin A.) After stimulation, cells are stained with any other antibodies of interest and then are analyzed by flow cytometry or purified by cell sorting. Unlike other assays, this method allows simultaneous assessment of other cell phenotypes or functions, is compatible with downstream RNA-based assays and preserves cell viability. This protocol can be completed in 9 h. C1 NIAID, Natl Inst Hlth, Vaccine Res Ctr, Immunotechnol Sect, Bethesda, MD 20892 USA. RP Chattopadhyay, PK (reprint author), NIAID, Natl Inst Hlth, Vaccine Res Ctr, Immunotechnol Sect, 40 Convent Dr, Bethesda, MD 20892 USA. EM pchattop@mail.nih.gov RI Chattopadhyay, Pratip/B-9227-2008; OI Chattopadhyay, Pratip/0000-0002-5457-9666 FU Intramural NIH HHS [Z99 AI999999] NR 14 TC 65 Z9 67 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 1 BP 1 EP 6 DI 10.1038/nprot.2006.1 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 232EX UT WOS:000251002200001 PM 17406204 ER PT J AU Lorenz, H Hailey, DW Wunder, C Lippincott-Schwartz, J AF Lorenz, Holger Hailey, Dale W. Wunder, Christian Lippincott-Schwartz, Jennifer TI The fluorescence protease protection (FPP) assay to determine protein localization and membrane topology SO NATURE PROTOCOLS LA English DT Article ID DEGRADATION; COMPARTMENT; TRANSPORT; CELLS AB Correct localization and topology are crucial for the cellular function of a protein. To determine the topology of membrane proteins, a new technique, called the fluorescence protease protection ( FPP) assay, can be applied. This assay uses the restricted proteolytic digestibility of GFP- tagged transmembrane proteins to indicate their intramembrane orientation. The sole requirements for FPP are the expression of GFP fusion proteins and the selective permeabilization of the plasma membrane, which permits a wide range of cell types and organelles to be investigated. The FPP assay can be carried out in a straightforward manner to obtain reliable results within minutes. Here we provide a step- by- step protocol for the assay. As an example, we use FPP to determine which terminus of an endoplasmic reticulum ( ER) transmembrane protein is lumenal and which one is facing the cytosol. C1 NICHHD, NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Lorenz, H (reprint author), NICHHD, NIH, Cell Biol & Metab Branch, Bldg 18T Lib Dr, Bethesda, MD 20892 USA. EM holgerl@mail.nih.gov OI Wunder, Christian/0000-0001-9091-0080 FU Intramural NIH HHS NR 7 TC 64 Z9 65 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 1 BP 276 EP 279 DI 10.1038/nprot.2006.42 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 232EX UT WOS:000251002200041 PM 17406244 ER PT J AU Usharauli, D Perez-Diez, A Matzinger, P AF Usharauli, David Perez-Diez, Ainhoa Matzinger, Polly TI The JAM Test and its daughter P-JAM: simple tests of DNA fragmentation to measure cell death and stasis SO NATURE PROTOCOLS LA English DT Article ID TUMOR-CELLS; ASSAY; APOPTOSIS AB Cytotoxic T lymphocytes, and other death-inducing agents, have at least two different ways of killing their targets: drilling holes in the target cell membrane, or triggering the targets to commit suicide. The JAM Test is a method that measures the DNA fragmentation that accompanies cell suicide. We label target cells with radioactive DNA-precursor nucleotides and harvest them onto fiberglass filters, which trap large pieces of DNA but pass smaller fragments of apoptotic cells. As a general measure of apoptosis, the JAM Test described here is faster (can be completed in 4 h [or less if labeling is done the night before]), more quantitative, easier, more sensitive, more flexible and cheaper than most other current assays of apoptosis. The P-JAM, also discussed, additionally allows for assessment of death in cells that don't fragment their DNA, and allows for assays of agents that induce cell stasis rather than death. C1 NIAID, NIH, Ghost Lab, Lab Cellular & Mol Immunol, Bethesda, MD 20892 USA. RP Matzinger, P (reprint author), NIAID, NIH, Ghost Lab, Lab Cellular & Mol Immunol, Bldg 4,Rm 111, Bethesda, MD 20892 USA. EM pcm@helix.nih.gov NR 6 TC 1 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 2 BP 673 EP U6 DI 10.1038/nprot.2006.107 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 232FA UT WOS:000251002500023 ER PT J AU Solinas, M Panlilio, LV Justinova, Z Yasar, S Goldberg, SR AF Solinas, Marcello Panlilio, Leigh V. Justinova, Zuzana Yasar, Sevil Goldberg, Steven R. TI Using drug-discrimination techniques to study the abuse-related effects of psychoactive drugs in rats SO NATURE PROTOCOLS LA English DT Article ID NUCLEUS-ACCUMBENS DOPAMINE; STIMULUS PROPERTIES; (R)-METHANANDAMIDE GENERALIZATION; ADENOSINERGIC MODULATION; TRACE DISCRIMINATION; INTRAVENOUS COCAINE; RECEPTOR SUBTYPES; FOOD-DEPRIVATION; INVOLVEMENT; CAFFEINE AB Drug-discrimination (DD) techniques can be used to study abuse-related effects by establishing the interoceptive effects of a training drug (e.g., cocaine) as a cue for performing a specific operant response (e.g., lever pressing reinforced by food). During training with this protocol, pressing one lever is reinforced when the training drug is injected before the start of the session, and responding on a second lever is reinforced when vehicle is injected before the session. Lever choice during test sessions can then be used as an indication of whether a novel drug has effects similar to the training drug, or whether a potential therapeutic alters the effects of the training drug. Although training can be lengthy (up to several months), the pharmacological specificity of DD procedures make them a perfect complement to other techniques used to study drug-abuse phenomena, such as intravenous self-administration and conditioned place-preference procedures. C1 Univ Poitiers, CNRS, UMR 6187, F-86022 Poitiers, France. NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. RP Solinas, M (reprint author), Univ Poitiers, CNRS, UMR 6187, 40 Ave Recteur Pineau, F-86022 Poitiers, France. EM marcello.solinas@univ-poitiers.fr; sgoldber@intra.nida.nih.gov RI Justinova, Zuzana/A-9109-2011; Solinas, Marcello/M-3500-2016 OI Justinova, Zuzana/0000-0001-5793-7484; Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS NR 71 TC 52 Z9 53 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 3 BP 1194 EP 1206 DI 10.1038/nprot.2006.167 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 234IT UT WOS:000251155400016 PM 17406402 ER PT J AU Lamoreaux, L Roederer, M Koup, R AF Lamoreaux, Laurie Roederer, Mario Koup, Richard TI Intracellular cytokine optimization and standard operating procedure SO NATURE PROTOCOLS LA English DT Article ID CD8(+) T-CELLS; POLYCHROMATIC FLOW-CYTOMETRY; IDENTIFICATION; DEGRANULATION; COMPENSATION; EXPRESSION; PHENOTYPE; MONENSIN; SURFACE; ASSAYS AB We describe here a method for optimizing the use of polychromatic flow cytometry (with up to 17 fluorochromes simultaneously) in surface and intracellular staining of human T lymphocytes. We will highlight and discuss how to procedurally optimize key steps in the experimental process before an intracellular cytokine staining assay protocol is finalized. These include but are not limited to the titration of monoclonal antibodies, use of a dead-cell discriminator and 'dump' channel, selection of a cytokine secretion inhibitor, selection of fixation and permeabilization reagents, and inclusion of compensation controls. Building on this basic protocol, we then establish a polychromatic assay designed to detect five separate functions of T lymphocytes (production of three cytokines and one chemokine, and degranulation) while simultaneously identifying multiple surface markers on the responding cells. C1 NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Lamoreaux, L (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM llamorea@mail.nih.gov NR 27 TC 129 Z9 132 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 3 BP 1507 EP 1516 DI 10.1038/nprot.2006.268 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 234IT UT WOS:000251155400055 PM 17406442 ER PT J AU Perfetto, SP Ambrozak, D Nguyen, R Chattopadhyay, P Roederer, M AF Perfetto, Stephen P. Ambrozak, David Nguyen, Richard Chattopadhyay, Pratip Roederer, Mario TI Quality assurance for polychromatic flow cytometry SO NATURE PROTOCOLS LA English DT Article ID T-CELLS; PROGRAM; ENUMERATION; SUBSETS; SYSTEM; IMPACT; NAIVE AB This protocol outlines a three-part quality assurance program to optimize, calibrate and monitor flow cytometers used to measure cells labeled with five or more fluorochromes (a practice known as polychromatic flow cytometry). The initial steps of this program (system optimization) ensure that the instrument's lasers, mirrors and filters are optimally configured for the generation and transmission of multiple fluorescent signals. To determine the sensitivity and dynamic range of each fluorescence detector, the system is then calibrated by measuring fluorescence over a range of photomultiplier tube (PMT) voltages by determining the PMT voltage range and linearity (Steps 2-10) and validating the PMT voltage (Steps 11-17). Finally, to ensure consistent performance, we provide procedures to monitor the precision, accuracy and sensitivity of fluorescence measurements over time. All three aspects of this program should be performed upon installation, or whenever changes occur along the flow cytometer's optical path. However, only a few of these procedures need to be carried out on a routine basis. C1 NIAID, Flow Cytometry Core Facil, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Perfetto, SP (reprint author), NIAID, Flow Cytometry Core Facil, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM sperfetto@mail.nih.gov RI Chattopadhyay, Pratip/B-9227-2008; OI Chattopadhyay, Pratip/0000-0002-5457-9666 NR 22 TC 106 Z9 109 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 3 BP 1522 EP 1530 DI 10.1038/nprot.2006.250 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 234IT UT WOS:000251155400057 PM 17406444 ER PT J AU Kato, T Date, T Murayama, A Morikawa, K Akazawa, D Wakita, T AF Kato, Takanobu Date, Tomoko Murayama, Asako Morikawa, Kenichi Akazawa, Daisuke Wakita, Takaji TI Cell culture and infection system for hepatitis C virus SO NATURE PROTOCOLS LA English DT Article ID EFFICIENT REPLICATION; SUBGENOMIC REPLICON; GENOME; LINES; RNA AB Hepatitis C virus (HCV) infection causes chronic liver disease and is a worldwide health problem. Despite ever-increasing demand for knowledge on viral replication and pathogenesis, detailed analysis has been hampered by a lack of efficient viral culture systems. We isolated HCV genotype 2a strain JFH-1 from a patient with fulminant hepatitis. This strain replicates efficiently in Huh7 cells. Efficient replication and secretion of recombinant viral particles can be obtained in cell culture by transfection of in vitro - transcribed full-length JFH-1 RNA into Huh7 cells. JFH-1 virus generated in cell culture is infectious for both naive Huh7 cells and chimpanzees. The efficiency of viral production and infectivity of generated virus is substantially improved with permissive cell lines. This protocol describes how to use this system, which provides a powerful tool for studying viral life cycle and for the construction of antiviral strategies and the development of effective vaccines. Viral particles can be obtained in 12 days with this protocol. C1 NIH, NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA. Natl Inst Infect Dis, Dept Virol, Tokyo 1628460, Japan. Toray Industries Ltd, Pharmaceut Res Labs, Kanagawa 2488555, Japan. RP Wakita, T (reprint author), NIH, NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA. EM wakita@nih.go.jp NR 12 TC 125 Z9 129 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 5 BP 2334 EP 2339 DI 10.1038/nprot.2006.395 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 234IV UT WOS:000251155600021 PM 17406476 ER PT J AU Blonder, J Chan, KC Issaq, HJ Veenstra, TD AF Blonder, Josip Chan, King C. Issaq, Haleem J. Veenstra, Timothy D. TI Identification of membrane proteins from mammalian cell/tissue using methanol-facilitated solubilization and tryptic digestion coupled with 2D-LC-MS/MS SO NATURE PROTOCOLS LA English DT Article ID IONIZATION MASS-SPECTROMETRY; PROTEOMIC ANALYSIS; TECHNOLOGY; GENOME; CELLS AB The core prerequisites for an efficient proteome-scale analysis of mammalian membrane proteins are effective isolation, solubilization, digestion and multidimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). This protocol is for analysis of the mammalian membrane proteome that relies on solubilization and tryptic digestion of membrane proteins in a buffer containing 60% (vol/vol) methanol. Tryptic digestion is followed by strong cation exchange (SCX) chromatography and reversed phase (RP) chromatography coupled online with MS/MS for protein identification. The use of a methanol-based buffer eliminates the need for reagents that interfere with chromatographic resolution and ionization of the peptides (e. g., detergents, chaotropes, inorganic salts). Sample losses are minimized because solubilization and digestion are carried out in a single tube avoiding any sample transfer or buffer exchange between these steps. This protocol is compatible with stable isotope labeling at the protein and peptide level, enabling identification and quantitation of integral membrane proteins. The entire procedure-beginning with isolated membrane fraction and finishing with MS data acquisition-takes 4-5 d. C1 Natl Canc Inst Frederick, SAIC Frederick Inc, Lab Proteom & Anal Technol, Frederick, MD 21702 USA. RP Blonder, J (reprint author), Natl Canc Inst Frederick, SAIC Frederick Inc, Lab Proteom & Anal Technol, POB B, Frederick, MD 21702 USA. EM blonder@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 27 TC 70 Z9 71 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 6 BP 2784 EP 2790 DI 10.1038/nprot.2006.359 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 234IW UT WOS:000251155700033 PM 17406535 ER PT J AU Padilla-Nash, HM Barenboim-Stapleton, L Difilippantonio, MJ Ried, T AF Padilla-Nash, Hesed M. Barenboim-Stapleton, Linda Difilippantonio, Michael J. Ried, Thomas TI Spectral karyotyping analysis of human and mouse chromosomes SO NATURE PROTOCOLS LA English DT Article ID HUMAN BREAST-CANCER; INSITU HYBRIDIZATION; CYTOGENETIC CHARACTERIZATION; PRENATAL-DIAGNOSIS; CELL-LINES; ABERRATIONS; TUMOR; TRANSLOCATIONS; ABNORMALITIES; LOCALIZATION AB Classical banding methods provide basic information about the identities and structures of chromosomes on the basis of their unique banding patterns. Spectral karyotyping (SKY), and the related multiplex fluorescence in situ hybridization (M-FISH), are chromosome-specific multicolor FISH techniques that augment cytogenetic evaluations of malignant disease by providing additional information and improved characterization of aberrant chromosomes that contain DNA sequences not identifiable using conventional banding methods. SKY is based on cohybridization of combinatorially labeled chromosome-painting probes with unique fluorochrome signatures onto human or mouse metaphase chromosome preparations. Image acquisition and analysis use a specialized imaging system, combining Sagnac interferometer and CCD camera images to reconstruct spectral information at each pixel. Here we present a protocol for SKY analysis using commercially available SkyPaint probes, including procedures for metaphase chromosome preparation, slide pretreatment and probe hybridization and detection. SKY analysis requires approximately 6 d. C1 NCI, US Natl Inst Hlth, Canc Res Ctr, Genet Branch, Bethesda, MD 20892 USA. RP Padilla-Nash, HM (reprint author), NCI, US Natl Inst Hlth, Canc Res Ctr, Genet Branch, 50 S Dr-MSC 8010, Bethesda, MD 20892 USA. EM nashh@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 34 TC 42 Z9 45 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2006 VL 1 IS 6 BP 3129 EP 3142 DI 10.1038/nprot.2006.358 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 234IW UT WOS:000251155700076 PM 17406576 ER PT J AU Colditz, GA Sellers, TA Trapido, E AF Colditz, GA Sellers, TA Trapido, E TI Epidemiology - identifying the causes and preventability of cancer? SO NATURE REVIEWS CANCER LA English DT Review ID HUMAN-PAPILLOMAVIRUS INFECTION; ESTROGEN PLUS PROGESTIN; BREAST-CANCER; COLORECTAL-CANCER; UNITED-STATES; LUNG-CANCER; COLLABORATIVE REANALYSIS; SOCIETY GUIDELINES; COST-EFFECTIVENESS; CONTROLLED-TRIALS AB It has been almost 25 years since Doll and Peto performed their landmark analysis of epidemiological data to identify the causes of cancers and possible modes of cancer prevention. Since then, there have been many additional studies of cancer incidence using various epidemiological techniques. These studies revealed expanded opportunities for cancer prevention through approaches that include vaccination, increased physical activity, weight control and avoidance of post- menopausal hormone therapy. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20852 USA. RP Colditz, GA (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM Graham.Colditz@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 110 TC 93 Z9 98 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JAN PY 2006 VL 6 IS 1 BP 75 EP 83 DI 10.1038/nrc1784 PG 9 WC Oncology SC Oncology GA 999QW UT WOS:000234406200016 PM 16372016 ER PT J AU Strober, W Murray, PJ Kitani, A Watanabe, T AF Strober, W Murray, PJ Kitani, A Watanabe, T TI Signalling pathways and molecular interactions of NOD1 and NOD2 SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID INTESTINAL EPITHELIAL-CELLS; NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; MURAMYL DIPEPTIDE RECOGNITION; HOST-MICROBIAL INTERACTIONS; INNATE IMMUNE-RESPONSES; HUMAN MONOCYTIC CELLS; LEUCINE-RICH REPEAT; CROHNS-DISEASE AB The NOD (nucleotide-binding oligomerization domain) proteins NOD1 and NOD2 have important roles in innate immunity as sensors of microbial components derived from bacterial peptidoglycan. The importance of these molecules is underscored by the fact that mutations in the gene that encodes NOD2 occur in a subpopulation of patients with Crohn's disease, and NOD1 has also been shown to participate in host defence against infection with Helicobacter pylori. Here, we focus on the molecular interactions between these NOD proteins and other intracellular molecules to elucidate the mechanisms by which NOD1 and NOD2 contribute to the maintenance of mucosal homeostasis and the induction of mucosal inflammation. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bldg 10 CRC,5W3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 97 TC 476 Z9 496 U1 10 U2 63 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2006 VL 6 IS 1 BP 9 EP 20 DI 10.1038/nri1747 PG 12 WC Immunology SC Immunology GA 000FW UT WOS:000234447300015 PM 16493424 ER PT J AU Zimmerberg, J Kozlov, MM AF Zimmerberg, J Kozlov, MM TI How proteins produce cellular membrane curvature SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID COATED VESICLE FORMATION; BIOLOGICAL-MEMBRANES; ELASTIC PROPERTIES; PHOSPHOLIPID-MEMBRANES; LYSOPHOSPHATIDIC ACID; BENDING ELASTICITY; PHOSPHATIDIC-ACID; FLUID MEMBRANES; MAMMALIAN GOLGI; COPII VESICLE AB Biological membranes exhibit various function-related shapes, and the mechanism by which these shapes are created is largely unclear. Here, we classify possible curvature-generating mechanisms that are provided by lipids that constitute the membrane bilayer and by proteins that interact with, or are embedded in, the membrane. We describe membrane elastic properties in order to formulate the structural and energetic requirements of proteins and lipids that would enable them to work together to generate the membrane shapes seen during intracellular trafficking. C1 NICHHD, Lab Cell & Mol Biophys, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Zimmerberg, J (reprint author), NICHHD, Lab Cell & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov; michk@post.tau.ac.il FU Intramural NIH HHS NR 99 TC 609 Z9 618 U1 18 U2 140 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 2006 VL 7 IS 1 BP 9 EP 19 DI 10.1038/nrm1784 PG 11 WC Cell Biology SC Cell Biology GA 015ZI UT WOS:000235589800010 PM 16365634 ER PT J AU Saxena, AK Singh, K Su, HP Klein, MM Stowers, AW Saul, AJ Long, CA Garboczi, DN AF Saxena, AK Singh, K Su, HP Klein, MM Stowers, AW Saul, AJ Long, CA Garboczi, DN TI The essential mosquito-stage P25 and P28 proteins from Plasmodium form tile-like triangular prisms SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID MALARIA; VACCINE; VIVAX; ANTIBODIES; OOKINETE; SURFACE AB P25 and P28 proteins are essential for Plasmodium parasites to infect mosquitoes and are leading candidates for a transmission-blocking malaria vaccine. The Plasmodium vivax P25 is a triangular prism that could tile the parasite surface. The residues forming the triangle are conserved in P25 and P28 from all Plasmodium species. A cocrystal structure shows that a transmission-blocking antibody uses only its heavy chain to bind Pvs25 at a vertex of the triangle. C1 NIAID, Struct Biol Sect, Immunogenet Lab, US NIH, Rockville, MD 20852 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Saxena, AK (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, Room 403,New Mehrauli Rd, New Delhi 110067, India. EM asaxena@mail.jnu.ac.in; dgarboczi@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Intramural NIH HHS NR 12 TC 31 Z9 32 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JAN PY 2006 VL 13 IS 1 BP 90 EP 91 DI 10.1038/nsmb1024 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 001TY UT WOS:000234561900018 PM 16327807 ER PT J AU Liu, Y Lan, Q Siegfried, JM Luketich, JD Keohavong, P AF Liu, Yang Lan, Qing Siegfried, Jill M. Luketich, James D. Keohavong, Phouthone TI Aberrant promoter methylation of p16 and MGMT genes in lung tumors from smoking and never-smoking lung cancer patients SO NEOPLASIA LA English DT Article DE lung tumors; p16; MGMT; promoter methylation; never-smokers ID FACTOR RECEPTOR GENE; K-RAS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; NONSMOKING WOMEN; DNA METHYLATION; CPG ISLANDS; HYPERMETHYLATION; MUTATIONS; INACTIVATION; P16(INK4A) AB Aberrant methylation in gene promoter regions leads to transcriptional inactivation of cancer-related genes and plays an integral role in tumorigenesis. This alteration has been investigated in lung tumors primarily from smokers, whereas only a few studies involved never-smokers. Here, we applied methylation-specific polymerase chain reaction to compare the frequencies of the methylated promoter of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) genes in lung tumors from 122 patients with non-small cell lung cancer, including 81 smokers and 41 never-smokers. Overall, promoter methylation was detected in 52.5% (64 of 122) and 30.3% ( 37 of 122) of the p16 and MGMT genes, respectively. Furthermore, the frequency of promoter methylation was significantly higher among smokers, compared with never-smokers, for both the p16 [odds ratio (OR) = 3.28; 95% confidence interval (CI) = 1.28-8.39; P = .013] and MGMT (OR = 3.93; 95% CI = 1.27-12.21; P = .018) genes. The trend for a higher promoter methylation frequency of these genes was also observed among female smokers compared with female never-smokers. Our results suggest an association between tobacco smoking and an increased incidence of aberrant promoter methylation of the p16 and MGMT genes in non-small cell lung cancer. C1 Univ Pittsburgh, Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15219 USA. NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. RP Keohavong, P (reprint author), Univ Pittsburgh, Sch Publ Hlth, Dept Environm & Occupat Hlth, Suite 350,Bridgeside Point,100 Technol Dr, Pittsburgh, PA 15219 USA. EM pho1@pitt.edu OI Keohavong, Phouthone/0000-0001-7812-4925 NR 32 TC 73 Z9 81 U1 0 U2 0 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN PY 2006 VL 8 IS 1 BP 46 EP 51 DI 10.1593/neo.05586 PG 6 WC Oncology SC Oncology GA 067AD UT WOS:000239271400006 PM 16533425 ER PT J AU Yan, Y Wang, Y Tan, Q Haray, Y Yun, TK Lubet, RA You, M AF Yan, Ying Wang, Yian Tan, Qing Haray, Yukihiko Yun, Taik-Koo Lubet, Ronald A. You, Ming TI Efficacy of polyphenon E, red ginseng, and rapamycin on benzo(a)pyrene-induced lung tumorigenesis in A/J mice SO NEOPLASIA LA English DT Article DE chemoprevention; lung tumor; polyphenon E; red ginseng; rapamycin ID ANTITUMOR-PROMOTING ACTIVITIES; ENVIRONMENTAL TOBACCO-SMOKE; GREEN TEA POLYPHENOLS; CA MEYER; CANCER CHEMOPREVENTION; MAMMALIAN TARGET; ACTIVE COMPOUNDS; NEWBORN MICE; S6 KINASE; BLACK TEA AB The objective of this investigation was to determine the efficacy of several novel agents in preventing lung tumorigenesis in mice. We evaluated polyphenon E, red ginseng, and rapamycin in A/J mice treated with the tobacco-specific carcinogen benzo( a) pyrene for their ability to inhibit pulmonary adenoma formation and growth. We found that treatment with polyphenon E exhibited a significant reduction on both tumor multiplicity and tumor load ( tumor multiplicity x tumor volume) in a dose-dependent fashion. Polyphenon E (2% wt/wt) in the diet reduced tumor multiplicity by 46% and tumor load by 94%. This result provided key evidence in support of a phase II clinical chemoprevention trial of lung cancer. Administration of red ginseng in drinking water decreased tumor multiplicity by 36% and tumor load by 70%. The mammalian target of rapamycin inhibitor rapamycin showed significant efficacy against lung tumor growth in the tumor progression protocol and reduced tumor load by 84%. The results of these investigations demonstrate that polyphenon E, red ginseng, and rapamycin significantly inhibit pulmonary adenoma formation and growth in A/J mice. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. Mitsui Norin Co Ltd, Shizuoka 42601, Japan. Korea Canc Ctr Hosp, Seoul 139706, South Korea. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, Campus Box 8109,660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [P01 CA9696401, R01 CA058554] NR 52 TC 43 Z9 45 U1 1 U2 2 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN PY 2006 VL 8 IS 1 BP 52 EP 58 DI 10.1593/neo.05652 PG 7 WC Oncology SC Oncology GA 067AD UT WOS:000239271400007 PM 16533426 ER PT J AU Perkins, RM Reynolds, JC Ahuja, TS Reid, T Agodoa, LY Bohen, EM Yuan, CM Abbott, KC AF Perkins, RM Reynolds, JC Ahuja, TS Reid, T Agodoa, LY Bohen, EM Yuan, CM Abbott, KC TI Thrombotic microangiopathy in United States long-term dialysis patients SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE dialysis; haemolytic uraemic syndrome (HUS); systemic lupus erythematosus; thrombotic thrombocytopenic purpura (TTP); thrombotic microangiopathy; United States Renal Data System (USRDS) ID HEMOLYTIC-UREMIC SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; THROMBOCYTOPENIC PURPURA AB Background. The incidence, risk factors, recurrence rates and prognosis of thrombotic microangiopathy (TMA) among long-term dialysis patients in the United States have not been previously described in a national population. Methods. 272 024 Medicare primary patients in the United States Renal Data System (USRDS) initiated on end-stage renal disease (ESRD) therapy between 1 April 1995 and 31 December 1999 with Medicare as primary payer were analysed in a retrospective cohort study of USRDS of TMA. Cox regression was used to calculate adjusted hazard ratios (AHR) for risk of TMA and risk of death after TMA. Results. The incidence of TMA in the first year of dialysis was 0.5% overall. Among patients with renal failure due to haemolytic uraemic syndrome (HUS), the incidence of TMA was highest in the first year of dialysis (HUS, 11.3% first year, 4.5% per year thereafter), while among patients without HUS the incidence of TMA was much lower and more constant over time (0.3% per year). In Cox regression analysis, independent risk factors for TMA were renal failure due to HUS (adjusted hazard ratio (AHR) 179, 95% CI 95-338), paediatric age (<= 18 years vs older, AHR 2.59, 95% CI 1.48-4.55), female gender (AHR 1.99, 95% CI 1.43-2.78), and systemic lupus erythematosus (SLE, AHR 3.66, 95% CI 1.49-8.51). One-year survival after TMA was poor at 58% (AHR for mortality 2.04, 95% CI 1.23-3.38). Conclusions. TMA is an uncommon cause of hospitalization after dialysis, but does recur in patients with HUS at a substantial rate. Younger age and SLE were risk factors for new onset TMA, which was associated with poor survival. Vigilant monitoring of select patients with HUS-related ESRD and higher-risk patients with SLE is warranted in the dialysis population. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Brooke Army Med Ctr, Serv Nephrol, Ft Sam Houston, TX 78234 USA. Univ Texas, Serv Nephrol, Galveston, TX 77555 USA. NIDDK, NIH, Bethesda, MD USA. RP Perkins, RM (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM robert.perkins@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 18 TC 6 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JAN PY 2006 VL 21 IS 1 BP 191 EP 196 DI 10.1093/ndt/gfi153 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 000BO UT WOS:000234436100035 PM 16204286 ER PT J AU Dear, JW Kobayashi, H Brechbiel, MW Star, RA AF Dear, James W. Kobayashi, Hisataka Brechbiel, Martin W. Star, Robert A. TI Imaging acute renal failure with polyamine dendrimer-based MRI contrast agents SO NEPHRON CLINICAL PRACTICE LA English DT Article DE MRI; kidney; imaging; acute renal failure; sepsis; biomarker ID MICRO-MRI; AGED MICE; SEPSIS; KIDNEY; DAMAGE; SIZES; CORES; TUMOR; DTPA AB Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF. This technique can diagnose early renal injury before serum creatinine is elevated, distinguish different ARF etiologies, track drug therapy and predict outcome. As an ARF biomarker, MRI with dendrimer-based contrast is a promising technique deserving further development. C1 NIDDK, Renal Diagnost & Therapeut Unit, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, NIH, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, 10 Ctr Dr,Bldg 10,Room 3N108, Bethesda, MD 20892 USA. EM starr@niddk.nih.gov FU Intramural NIH HHS NR 23 TC 24 Z9 25 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2006 VL 103 IS 2 BP C45 EP C49 DI 10.1159/000090608 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 163PY UT WOS:000246174900005 PM 16543755 ER PT J AU Monkawa, T Pippin, J Yo, Y Kopp, JB Alpers, CE Shankland, SJ AF Monkawa, T Pippin, J Yo, Y Kopp, JB Alpers, CE Shankland, SJ TI The cyclin-dependent kinase inhibitor p21 limits murine mesangial proliferative glomerulonephritis SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE cyclin kinase inhibitor; p21; glomerulonephritis; cell cycle ID EPITHELIAL-CELL PROLIFERATION; ACUTE-RENAL-FAILURE; IN-VIVO; APOPTOSIS; EXPRESSION; P21(WAF1/CIP1); NEPHROPATHY; HYPERTROPHY; RESOLUTION; GLOMERULI AB Background: Mesangial cell ( MC) proliferation underlies increased matrix accumulation in glomerulonephritis (GN), and the resolution of MC proliferation occurs largely through apoptosis. Proliferation and apoptosis are controlled by specific cell cycle proteins, where cyclin-dependent kinase (CDK) inhibitors such as p21 bind target cyclin-CDK complexes. However, the role of p21 in acute mesangial proliferative GN is not known. This study was conducted to test the hypothesis that p21 regulates MC proliferation and apoptosis in anti-MC serum-induced GN. Methods: Age and sex matched wild-type (p21 +/+) and p21-deficient (p21 -/-) mice were injected with sheep anti-MC serum. Renal function (BUN, urinary albumin excretion), histology, DNA synthesis ( BrdU. Ki67) and apoptosis (TUNEL) were quantified at day 6 and day 12 (n = 6-8/time point). Results: In p21 +/+ mice, anti-MC serum induced mild MC proliferative GN, and glomerular p21 expression was increased. Renal function was worse in nephric p21 -/- mice. PAS and silver staining revealed that p21 -/- mice had typical features of MC proliferative GN with focal segmental tuft necrosis, focal mesangiolysis and focal mesangial hypercellularity. Occasional features of podocyte injury (swelling, vacuolization) were noted. Double immunostaining confirmed increased mesangial cell DNA synthesis in nephritic p21 -/- mice at day 6. In contrast, there was no difference in glomerular apoptosis in nephritic p21 +/+ and p21 -/- mice at each time point. Glomerular lesions were accompanied by severe glomerular and tubulointerstitial fibrosis in p21 -/- mice. Conclusions: This data shows that the CDK-inhibitor p21 regulates the MC proliferative response to immune-mediated injury. In contrast, p21 does not alter the apoptotic response, resulting in a delayed resolution in nephritic p21 -/- mice. Copyright (c) 2006 S. Karger AG, Basel. C1 Univ Washington, Div Nephrol, Med Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan. RP Shankland, SJ (reprint author), Univ Washington, Div Nephrol, Med Ctr, Box 356521, Seattle, WA 98195 USA. EM stuartjs@u.washington.edu RI Monkawa, Toshiaki/F-2361-2010; OI Monkawa, Toshiaki/0000-0002-7876-7661; Kopp, Jeffrey/0000-0001-9052-186X NR 24 TC 5 Z9 9 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PY 2006 VL 102 IS 1 BP E8 EP E18 DI 10.1159/000088311 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 985GH UT WOS:000233364400002 PM 16179805 ER PT J AU Hoorn, EJ Hoffert, JD Knepper, MA AF Hoorn, Ewout J. Hoffert, Jason D. Knepper, Mark A. TI The application of DIGE-based proteomics to renal physiology SO NEPHRON PHYSIOLOGY LA English DT Article ID DIFFERENCE GEL-ELECTROPHORESIS; MEDULLARY COLLECTING DUCT; SYSTEMS BIOLOGY; 2-DIMENSIONAL ELECTROPHORESIS; SIGNALING NETWORKS; MEMBRANE-PROTEINS; MASS-SPECTROMETRY; VASOPRESSIN; KIDNEY; PHOSPHOPROTEOME AB Proteomics is seeing increasing use as a means of identifying new mechanistic hypotheses in physiology. Proteomics based on two-dimensional electrophoresis (2DE) has recently been optimized with the development of Difference Gel Electrophoresis (DIGE). In DIGE-based proteomics, the experimental and control samples are derivatized with different fluorophores and are run in the same gel, thereby minimizing technical variation. DIGE is currently one of the few techniques to perform quantitative proteomics, generating a statistical output to differences in protein abundances. In this review, we discuss the principles of DIGE-based proteomics, including sample preparation, 2-DE, statistical analysis of 2D-gels, and mass spectrometry. Strengths and weaknesses of DIGE are discussed, including possible solutions to overcome certain limitations, such as the identification of low abundance and integral membrane proteins. In addition, we provide a brief synopsis of our recent experiments in which DIGE-based proteomics was applied to study vasopressin signaling in the renal collecting duct. Finally, we illustrate how quantification based on the DIGE approach combined with bioinformatics may facilitate the study of systems biology of the kidney. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Room 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov NR 56 TC 20 Z9 22 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2137 J9 NEPHRON PHYSIOL JI Nephron Physiol. PY 2006 VL 104 IS 1 BP 61 EP 72 DI 10.1159/000093288 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 099RH UT WOS:000241612600006 ER PT J AU Kleta, R Bockenhauer, D AF Kleta, Robert Bockenhauer, Detlef TI Bartter syndromes and other salt-losing tubulopathies SO NEPHRON PHYSIOLOGY LA English DT Review ID FANCONI SYNDROME; MUTATIONS; TRANSPORT; REABSORPTION; DEAFNESS; RECEPTOR; KINASE; GENE AB Genetic studies into rare inborn errors of renal tubular sodium handling in man have brought many interesting, sometimes surprising insights into how we can maintain our bodies' electrolytes and fluids homeostasis. The cloning and identification of sodium transporting genes and proteins like NHE3, NKCC2, ROMK, CLCNKB, NCC, and EnaC has considerably improved our understanding of renal salt handling. Subsequently, studies of genetically engineered animals provided even more insight into the complex renal physiology. The recent discovery of the WNK kinases as regulators and integrators of specific c renal transport pathways helped elucidate this further and lets us start to appreciate the full complexity of renal sodium handling. We summarize recent findings in the field in the context of human diseases and a pathophysiologic basis for their treatment. Copyright (c) 2006 S. Karger AG, Basel. RP Kleta, R (reprint author), NHGRI, MGB, SHBG, NIH, Bldg 10,Room 10C103C,MSC 1851,10 Ctr Dr, Bethesda, MD 20892 USA. EM kletar@mail.nih.gov RI Bockenhauer, Detlef/C-5951-2008 OI Bockenhauer, Detlef/0000-0001-5878-941X FU Intramural NIH HHS NR 17 TC 49 Z9 55 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2137 J9 NEPHRON PHYSIOL JI Nephron Physiol. PY 2006 VL 104 IS 2 BP 73 EP 80 DI 10.1159/000094001 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 099RI UT WOS:000241612700001 PM 16785747 ER PT B AU Welsh, CJ Meagher, MW Sternberg, EM AF Welsh, C. Jane Meagher, Mary W. Sternberg, Esther M. BE Welsh, CJ Meagher, MW Sternberg, EM TI Neural and neuroendocrine mechanisms in host defense and autoimmunity SO NEURAL AND NEUROENDOCRINE MECHANISMS IN HOST DEFENSE AND AUTOIMMUNITY LA English DT Proceedings Paper CT Symposium on Neural and Neuroendocrine Mechanisms in Host Defense and Autoimmunity CY MAY 06-10, 2003 CL Denver, CO SP Int Soc Neuroimmuno Modulat C1 [Welsh, C. Jane] Texas A&M Univ, Dept Vet Intergrative Biosci & Vet Pathobiol, College Stn, TX USA. [Sternberg, Esther M.] NIH, NIMH, Sect Neuroendoocrine Immunol & Behav, Bethesda, MD USA. [Welsh, C. Jane] Texas A&M Univ, Coll Vet Med & Biomed Sci, College Stn, TX 77843 USA. [Meagher, Mary W.] Texas A&M Univ, Coll Lib Arts, Dept Psychol, College Stn, TX 77843 USA. RP Welsh, CJ (reprint author), Texas A&M Univ, Dept Vet Intergrative Biosci & Vet Pathobiol, College Stn, TX USA. EM jwelsh@cvm.tamu.edu; m-meagher@tamu.edu; ems@codon.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-31411-3 PY 2006 BP 1 EP 4 PG 4 WC Endocrinology & Metabolism; Immunology; Infectious Diseases; Clinical Neurology SC Endocrinology & Metabolism; Immunology; Infectious Diseases; Neurosciences & Neurology GA BFD38 UT WOS:000241155400001 ER PT B AU Webster, JI Moayeri, M Sternberg, EM AF Webster, Jeanette I. Moayeri, Mahtab Sternberg, Esther M. BE Welsh, CJ Meagher, MW Sternberg, EM TI Anthrax lethal factor represses glucocorticoid and progesterone receptor activity SO NEURAL AND NEUROENDOCRINE MECHANISMS IN HOST DEFENSE AND AUTOIMMUNITY LA English DT Proceedings Paper CT Symposium on Neural and Neuroendocrine Mechanisms in Host Defense and Autoimmunity CY MAY 06-10, 2003 CL Denver, CO SP Int Soc Neuroimmuno Modulat ID PITUITARY-ADRENAL AXIS; CHRONIC-FATIGUE-SYNDROME; 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; CORTICOTROPIN-RELEASING HORMONE; BLOOD MONONUCLEAR-CELLS; RHEUMATIC AUTOIMMUNE DISORDERS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY-BOWEL-DISEASE; TOXIN PROTECTIVE ANTIGEN; P-GLYCOPROTEIN ACTIVITY C1 [Webster, Jeanette I.; Sternberg, Esther M.] NIH, Sect Euroendocrine Immunol & Behav, NIMH, Rockville, MD 20892 USA. [Moayeri, Mahtab] NIH, NIAID, Bethesda, MD 20892 USA. RP Webster, JI (reprint author), NIH, Sect Euroendocrine Immunol & Behav, NIMH, Rockville, MD 20892 USA. RI Webster Marketon, Jeanette/H-5613-2011 OI Webster Marketon, Jeanette/0000-0002-3627-1094 NR 175 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-31411-3 PY 2006 BP 57 EP 80 DI 10.1007/978-0-387-48334-4_4 PG 24 WC Endocrinology & Metabolism; Immunology; Infectious Diseases; Clinical Neurology SC Endocrinology & Metabolism; Immunology; Infectious Diseases; Neurosciences & Neurology GA BFD38 UT WOS:000241155400004 ER PT J AU Sargent, TD AF Sargent, Thomas D. TI Transcriptional regulation at the neural plate border SO NEURAL CREST INDUCTION AND DIFFERENTIATION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID FACTOR AP-2; HOMEODOMAIN PROTEIN; MODIFIED OLIGONUCLEOTIDES; CRANIOFACIAL DEVELOPMENT; VERTEBRATE DEVELOPMENT; DLX HOMEOPROTEINS; CREST DEVELOPMENT; ZEBRAFISH TFAP2A; HOMEOBOX GENES; XENOPUS-LAEVIS C1 NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA. EM sargentt@mail.nih.gov NR 61 TC 5 Z9 5 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 589 BP 32 EP 44 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFE64 UT WOS:000241486600003 PM 17076274 ER PT J AU Silver, DL Hou, L Pavan, WJ AF Silver, Debra L. Hou, Ling Pavan, William J. TI The genetic regulation of pigment cell development SO NEURAL CREST INDUCTION AND DIFFERENTIATION SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID NEURAL CREST DEVELOPMENT; ENDOTHELIN-B RECEPTOR; TRANSCRIPTION FACTOR FOXD3; MELANOCYTE DEVELOPMENT; C-KIT; WAARDENBURG-SYNDROME; MOUSE EMBRYO; MELANOBLAST MIGRATION; AVIAN EMBRYO; IN-VITRO AB Pigment cells in developing vertebrates are derived from a transient and pluripotent population of cells called neural crest. The neural crest delaminates from the developing neural tube and overlying ectoderm early in development. The pigment cells are the only derivative to migrate along the dorso-lateral pathway. As they migrate, the precursor pigment cell population differentiates and expands through proliferation and pro-survival processes, ultimately contributing to the coloration of organisms. The types of pigment cells that develop, timing of these processes, and final destination can vary between organisms. Studies from mice, chick, Xenopus, zebrafish, and medaka have led to the identification of many genes that regulate pigment cell development. These include several classes of proteins: transcription factors, transmembrane receptors, and extracellular ligands. This chapter discusses an overview of pigment cell development and the genes that regulate this important process. C1 NHGRI, Genet Dis Branch, NIH, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NHGRI, Genet Dis Branch, NIH, Room 4A51,Bldg 49,49 Convent Dr, Bethesda, MD 20892 USA. EM bpavan@nhgri.nih.gov OI Hou, Ling/0000-0003-0705-8099 NR 141 TC 16 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 589 BP 155 EP 169 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BFE64 UT WOS:000241486600009 PM 17076280 ER PT J AU Soderlund, H Nilsson, LG Berger, K Breteler, MM Dufouil, C Fuhrer, R Giampaoli, S Hofman, A Pajak, A de Ridder, M Sans, S Schmidt, R Launer, LJ AF Soderlund, H Nilsson, LG Berger, K Breteler, MM Dufouil, C Fuhrer, R Giampaoli, S Hofman, A Pajak, A de Ridder, M Sans, S Schmidt, R Launer, LJ TI Cerebral changes on MRI and cognitive function: The CASCADE study SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; MRI; white matter hyperintensities; atrophy; cognition ID WHITE-MATTER LESIONS; MINI-MENTAL-STATE; ELDERLY-PEOPLE; ROTTERDAM SCAN; BRAIN-LESIONS; DEMENTIA; ATROPHY; POPULATION; SPEED; PET AB The aging, non-demented brain undergoes several physiological changes, some of which may affect cognitive function. The goal of the present study was to examine the associations between subcortical and periventricular white matter hyperimensities (WMHs), cortical and subcortical atrophy, and cognitive function (episodic memory, word fluency, attention, and perceptual, cognitive, and motor speed). This was done within a European collaborative study, Cardiovascular Determinants of Dementia (CASCADE), in which magnetic resonance imaging (MRI) was performed on community-dwelling individuals. The study includes 1254 persons from eight European study centers, ranging between 64 and 76 years of age (M 69.4 +/- 3.3; 55% men). When demographics (age, education, and sex), study center, and concurrent brain changes had been adjusted for, periventricular WMHS predicted lower performance in word fluency and the Stroop test (time), and subcortical atrophy predicted lower performance in motor speed and the Stroop test (errors). The findings are consistent with findings from lesion and functional neuroimaging studies. (C) 2005 Elsevier Inc. All rights reserved. C1 Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. Univ Munster, Inst Epidemiol & Social Med, Munster, Germany. Erasmus Univ, Sch Med, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Hop La Pitie Salpetriere, INSERM, U169, Paris, France. McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. Natl Inst Hlth, Rome, Italy. Jagiellonian Univ, Coll Med, Dept Clin Epidemiol & Populat Studies, Krakow, Poland. Inst Hlth Studies, Dept Hlth & Social Secur, Barcelona, Spain. Karl Franzens Univ Graz, Dept Neurol, A-8010 Graz, Austria. NIA, Lab Epidemiol Demog Biometry, Bethesda, MD 20892 USA. UCL, Dept Epidemiol & Publ Hlth, London, England. RP Soderlund, H (reprint author), Baycrest Ctr Geriatr Care, Rotman Res Inst, Toronto, ON, Canada. EM hedvig@rotman-baycrest.on.ca RI Dufouil, Carole/J-4968-2012; Soderlund, Hedvig/B-4060-2013; Breteler, Monique /J-5058-2014 NR 45 TC 49 Z9 52 U1 0 U2 6 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 2006 VL 27 IS 1 BP 16 EP 23 DI 10.1016/j.neurobiolaging.2004.12.008 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 998YM UT WOS:000234355800003 PM 16298236 ER PT J AU Garcia, ML Singleton, AB Hernandez, D Ward, CM Evey, C Sapp, PA Hardy, J Brown, RH Cleveland, DW AF Garcia, ML Singleton, AB Hernandez, D Ward, CM Evey, C Sapp, PA Hardy, J Brown, RH Cleveland, DW TI Mutations in neurofilament genes are not a significant primary cause of non-SOD1-mediated amyotrophic lateral sclerosis SO NEUROBIOLOGY OF DISEASE LA English DT Article DE ALS; motor neuron diseased; neurofilaments; SOD1; mutation ID MARIE-TOOTH-DISEASE; MOTOR-NEURON DISEASE; MUTANT SUPEROXIDE-DISMUTASE; SUBUNIT-NF-L; MOUSE MODEL; LIGHT GENE; HEAVY GENE; AXONAL NEUROFILAMENTS; SEQUENCE VARIANTS; PERIPHERIN AB While 1 to 2% of amyotrophic lateral sclerosis (ALS) is caused by mutations in the SOD1 gene, the basis of the remaining instances of inherited disease is unknown. Neuropathology, mouse modeling, and human genetics have implicated neurofilaments in the pathogenesis of motor neuron diseases such as ALS and Charcot - Marie- Tooth disease (CMT). A systematic analysis of the coding region and intron-exon boundaries of all three neurofilament genes is now reported from DNA samples derived from more than 200 non-SOD1 linked familial and sporadic ALS patients, along with > 400 non-disease control individuals. Rare variants within each of the three neurofila- ment subunits that are predicted to affect neurofilament assembly properties were identified at higher frequency in non-SOD1 mutant ALS samples. However, none could be unambiguously linked to dominantly inherited disease. Thus, mutations in neurofilaments are possible risk factors that may contribute to pathogenesis in ALS in conjunction with one or more additional genetic or environmental factors, but are not significant primary causes of ALS. Published by Elsevier Inc. C1 Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. NIA, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp East, Cecil B Day Lab Neuromuscular Res, Boston, MA 02129 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cleveland, DW (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, 9500 Gilman Dr,CMM-E Room 3072, La Jolla, CA 92093 USA. EM dcleveland@ucsd.edu RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 FU NINDS NIH HHS [R37 NS027036] NR 52 TC 23 Z9 25 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JAN PY 2006 VL 21 IS 1 BP 102 EP 109 DI 10.1016/j.nbd.2005.06.016 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 000KP UT WOS:000234460800011 PM 16084104 ER PT J AU Chen, ZY Warin, R Noguchi, CT AF Chen, Zhi-Yong Warin, Renaud Noguchi, Constance Tom TI Erythropoietin and normal brain development: Receptor expression determines multi-tissue response SO NEURODEGENERATIVE DISEASES LA English DT Article DE erythropoietin; brain development; hypoxic stress; erythropoiesis ID ENDOTHELIAL-CELLS; PROGENITORS; GENE; MICE; MOUSE AB Erythropoietin (EPO) is a hypoxia-inducible hormone required for erythroid differentiation. Expression of the EPO receptor is not restricted to hematopoietic cells and exhibits a multi-tissue distribution that includes neural cells, vascular endothelium and muscle progenitor cells. The ability for EPO to stimulate progenitor cell proliferation and prevent apoptosis is critical for maintenance of the erythroid lineage, but is also observed in neural and muscle progenitor cells. Mice lacking the EPO receptor die in utero due to severe anemia. However, even prior to lack of erythroid cell production in the embryo proper, these mice exhibit increased apoptosis in the brain as early as E10.5 and a reduction in the number of neural progenitor cells. Corresponding cultures of primary neural cells exhibit decreased neuron generation and increased sensitivity to reduced oxygen tension, and neurons do not survive after 24 h at low oxygen tension. In contrast, hypoxia induces EPO and EPO receptor in wildtype neuronal cells, and EPO enhances neuron survival at low oxygen tension. In vivo EPO is neuroprotective in adult animal models for brain ischemia. Induction of EPO and its receptor by hypoxia likely contributes to its neuroprotective activity and selective cell survival in the brain during hypoxic stress. Copyright (C) 2006 S. Karger AG, Basel. C1 NIDDKD, Mol Cell Biol Branch, NIH, Bethesda, MD 20892 USA. RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bldg 10,Room 9N307,10 Ctr DR MSC-1822, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov FU Intramural NIH HHS NR 21 TC 22 Z9 23 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2006 VL 3 IS 1-2 BP 68 EP 75 DI 10.1159/000092096 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 148ZF UT WOS:000245115200011 PM 16909040 ER PT J AU Shin, S Rao, MS AF Shin, Soojung Rao, Mahendra S. TI Large-scale analysis of neural stem cells and progenitor cells SO NEURODEGENERATIVE DISEASES LA English DT Article DE serial analysis of gene expression; neural stem cells; progenitor cells; expressed sequence tag scan; massively parallel signature sequencing; microarray ID GENE-EXPRESSION; SERIAL ANALYSIS; PRECURSOR CELLS; ARRAYS; DIFFERENTIATION; DISCOVERY; CANCER AB The past few years have seen remarkable progress in our understanding of stem cell biology. The wealth of genomic data and the multiplicity of sources have enabled researchers to begin to profile stem cells in detail. In this paper we describe the biological and technical controls necessary to obtain reliable data and the relative merits of various large-scale analytical techniques including microarray, expressed sequence tag enumeration, serial analysis of gene expression and massively parallel signature sequencing. We suggest that while much has been learned, additional information remains to be gleaned by meta-analysis of existing data. Copyright (C) 2006 S. Karger AG, Basel. C1 NIA, Gerontol Res Ctr, Stem Cell Biol Unit,Lab Neurosci, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. Invitrogen Corp, Corp Res Labs, Carlsbad, CA USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Stem Cell Biol Unit,Lab Neurosci, NIH, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov FU Intramural NIH HHS NR 19 TC 5 Z9 5 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 2006 VL 3 IS 1-2 BP 106 EP 111 DI 10.1159/000092101 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 148ZF UT WOS:000245115200016 PM 16909045 ER PT J AU Momeni, P Rogaeva, E Van Deerlin, V Yuan, WX Grafman, J Tierney, M Huey, E Bell, J Morris, CM Kalaria, RN van Rensburg, SJ Niehaus, D Potocnik, F Kawarai, T Salehi-Rad, S Sato, C George-Hyslop, PS Hardy, J AF Momeni, Parastoo Rogaeva, Ekaterina Van Deerlin, Vivianna Yuan, Wuxing Grafman, Jordan Tierney, Michael Huey, Edward Bell, Jason Morris, Chris M. Kalaria, Rajesh N. van Rensburg, Susan J. Niehaus, Dana Potocnik, Felix Kawarai, Toshitaka Salehi-Rad, Shabnam Sato, Christine George-Hyslop, Peter St. Hardy, John TI Genetic variability in CHMP2B and frontotemporal dementia SO NEURODEGENERATIVE DISEASES LA English DT Article DE frontotemporal dementia; chromosome 3; MAPT; CHMP2B ID MUTATIONS AB A nonsense/protein chain-terminating mutation in the CHMP2B gene has recently been reported as a cause of frontotemporal dementia (FTD) in the single large family known to show linkage to chromosome 3. Screening for mutations in this gene in a large series of FTD families and individual patients led to the identification of a protein-truncating mutation in 2 unaffected members of an Afrikaner family with FTD, but not in their affected relatives. The putative pathogenicity of CHMP2B mutations for dementia is discussed. Copyright (c) 2006 S. Karger AG, Basel. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. Univ Penn, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis, Philadelphia, PA 19104 USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Newcastle Gen Hosp, Inst Hlth & Ageing, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Newcastle Gen Hosp, Hlth Protect Agcy, Chem Hazards & Poisons Div, Wolfson Unit Chem Pharmacol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Stellenbosch, Dept Psychiat, ZA-7505 Tygerberg, South Africa. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Hardy, John/C-2451-2009; OI Grafman, Jordan H./0000-0001-8645-4457 FU Medical Research Council [G0400074, G0502157, G0701075]; NINDS NIH HHS [K08-NS14108] NR 8 TC 29 Z9 31 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2006 VL 3 IS 3 BP 129 EP 133 DI 10.1159/000094771 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 150HI UT WOS:000245206000002 PM 16954699 ER PT J AU Marlowe, L Peila, R Benke, KS Hardy, J White, LR Lenore, JL Myers, A AF Marlowe, Lauren Peila, Rita Benke, Kelly Suzanne Hardy, John White, Lon R. Launer, Lenore J. Myers, Amanda TI Insulin-degrading enzyme haplotypes affect insulin levels but not dementia risk SO NEURODEGENERATIVE DISEASES LA English DT Article DE Alzheimer's disease; insulin; IDE; epidemiology ID JAPANESE-AMERICAN MEN; AMYLOID BETA-PROTEIN; ALZHEIMERS-DISEASE; LINKAGE PHASE; GENE; IDE; POLYMORPHISMS; ASSOCIATION; DEGRADATION; DIAGNOSIS AB Background: Insulin-degrading enzyme (IDE) polymorphism is hypothesized to regulate insulin levels as well as processes involved in neuronal compromise found in dementia. Methods: We examined the association of IDE haplotypes with dementia and insulin levels in a single well-characterized cohort of Japanese-American men born between 1900 and 1919 and followed since 1965. In 1991, a fasting insulin was obtained; dementia cases were ascertained in 1991 and 1994 in a multi-stage procedure, diagnoses were made according to international guidelines. Five single-nucleotide polymorphisms were genotyped and used for haplotype analysis in a sample of 179 Alzheimer's disease cases, 104 vascular dementia cases and 516 controls nested in the total cohort. Results: The global test for the haplotype effect on insulin levels was significant (p < 0.0001), adjusting for age, education, apolipoprotein epsilon 4 status and fasting glucose. Conclusion: There was no association of IDE haplotypes with the risk of dementia. This study suggests IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimer's. Copyright (c) 2006 S. Karger AG, Basel. C1 NIA, LEDB, Intramural Res Program, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. Pacific Hlth Res Inst, Honolulu, HI USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Lenore, JL (reprint author), NIA, LEDB, Intramural Res Program, 7201 Wisconsin Ave,Rm 3C-309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009 OI Myers, Amanda/0000-0002-3100-9396; FU Medical Research Council [G0701075]; NHLBI NIH HHS [N01-HC-0-5102]; NIA NIH HHS [N01-AG-4-2149, R01AG-0-7155-06A1, U01-AG-0-9349-03] NR 26 TC 13 Z9 15 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2006 VL 3 IS 6 BP 320 EP 326 DI 10.1159/000097300 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 150HO UT WOS:000245206600002 PM 17192720 ER PT J AU Fung, HC Xiromerisiou, G Gibbs, JR Wu, YR Eerola, J Gourbali, V Hellstrom, O Chen, CM Duckworth, J Papadimitriou, A Tienari, PJ Hadjigeorgiou, GM Hardy, J Singleton, AB AF Fung, H. C. Xiromerisiou, G. Gibbs, J. R. Wu, Y. R. Eerola, J. Gourbali, V. Hellstrom, O. Chen, C. M. Duckworth, J. Papadimitriou, A. Tienari, P. J. Hadjigeorgiou, G. M. Hardy, J. Singleton, A. B. TI Association of tau haplotype-tagging polymorphisms with Parkinson's disease in diverse ethnic Parkinson's disease cohorts SO NEURODEGENERATIVE DISEASES LA English DT Article DE tau protein; MAPTpolymorphisms; Parkinson's disease; haplotype H1 ID PROGRESSIVE SUPRANUCLEAR PALSY; ALPHA-SYNUCLEIN; CORTICOBASAL DEGENERATION; LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; LEWY BODIES; DEMENTIA; FTDP-17 AB Background: The overlap in the clinical and pathological features of tauopathies and synucleinopathies raises the possibility that the tau protein may be important in Parkinson's disease (PD) pathogenesis. Several MAPT polymorphisms that define the tau H1 haplotype have been investigated for an association with PD with conflicting results; however, two meta-analyses support an association between haplotype H1 and PD. Methods: In this study, we recruited 508 patients and 611 healthy controls from Greek, Finnish and Taiwanese populations. We examined the possible genetic role of variation within MAPT in PD using haplotype-tagging single polymorphisms (SNPs) in these ethnically different PD populations. Results: We identified a moderate association at SNP rs3785883 in the Greek cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively) as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p = 0.04 allelic) in the Finnish population. There were no significant differences in genotype or allele distribution between cases and controls in the Taiwanese cohort. Conclusion:We failed to demonstrate a consistent association between the MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically diverse populations. However, the data presented here suggest that subhaplotypes of haplotype H1 may confer susceptibility to PD, and that either allelic heterogeneity or different haplotype composition explain the divergent haplotype results. Copyright (c) 2006 S. Karger AG, Basel. C1 NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Studies, London, England. Chang Gung Mem Hosp, Dept Neurol, Taipei 10591, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. Univ Thessaly, Sch Med, Dept Neurol, Neurogenet Unit, Larisa, Greece. Seinajoki Cent Hosp, Dept Neurol, Seinajoki, Finland. Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. Univ Helsinki, Biomedicum Helsinki, Neurosci Programme, Helsinki, Finland. RP Singleton, AB (reprint author), NIA, Mol Genet Unit, Neurogenet Lab, NIH, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM Singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Gibbs, J. Raphael/A-3984-2010; Tienari, Pentti/A-4893-2012; Hardy, John/C-2451-2009 FU Medical Research Council [G0701075] NR 24 TC 25 Z9 26 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2006 VL 3 IS 6 BP 327 EP 333 DI 10.1159/000097301 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 150HO UT WOS:000245206600003 PM 17192721 ER PT S AU Moutsopoulos, NM Madianos, PN AF Moutsopoulos, Niki M. Madianos, Phoebus N. BE Chrousos, GP Kaltsas, GA Mastorakos, G TI Low-grade inflammation in chronic infectious diseases - Paradigm of periodontal infections SO NEUROENDOCRINE AND IMMUNE CROSSTALK SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th Meeting of the International-Society-for-Neuroimmunomodulation - Neuroendocrine and Immune Crosstalk CY SEP 25-28, 2005 CL Athens, GREECE SP Novartis, Ipsen PC DE periodontitis; acute myocardial infarction (AMI) ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; LOW-BIRTH-WEIGHT; CARDIOVASCULAR-DISEASE; SYSTEMIC INFLAMMATION; ENDOTHELIAL DYSFUNCTION; PRETERM BIRTH; MARKERS; RISK; ASSOCIATION AB Increasing evidence implicates periodontitis, a chronic inflammatory disease of the tooth-supporting structures, as a potential risk factor for increased morbidity or mortality for several systemic conditions including cardiovascular disease (atherosclerosis, heart attack, and stroke), pregnancy complications (spontaneous preterm birth [SPB]), and diabetes mellitus. Cross-sectional, case-control, and cohort studies indicate that periodontitis may confer two- and up to sevenfold increase in the risk for cardiovascular disease and premature birth, respectively. Given the recently acquired knowledge that systemic inflammation may contribute in the pathogenesis of atherosclerosis and may predispose to premature birth, research in the field of periodontics has focused on the potential of this chronic low-grade inflammatory condition to contribute to the generation of a systemic inflammatory phenotype. Consistent with this hypothesis clinical studies demonstrate that periodontitis patients have elevated markers of systemic inflammation, such as C-reactive protein (CRP), interleukin 6 (IL-6), haptoglobin, and fibrinogen. These are higher in periodontal patients with acute myocardial infarction (AMI) than in patients with AMI alone, supporting the notion that periodontal disease is an independent contributor to systemic inflammation. In the case of adverse pregnancy outcomes, studies on fetal cord blood from SBP babies indicate a strong in utero IgM antibody response specific to several oral periodontal pathogens, which induces an inflammatory response at the fetal-placental unit, leading to prematurity. The importance of periodontal infections to systemic health is further strengthened by pilot intervention trials indicating that periodontal therapy may improve surrogate cardiovascular outcomes, such as endothelial function, and may reduce four- to fivefold the incidence of premature birth. Nevertheless, further research is needed to fully discern the underlying mechanisms by which local chronic infections can have an impact on systemic health, and in this endeavor periodontal disease may serve as an ideal disease model. C1 Univ Athens, Sch Dent, Dept Periodontol, Athens, Greece. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Madianos, PN (reprint author), Univ Athens, Sch Dent, Dept Periodontol, Thivon 2, Athens, Greece. EM pmadian@dent.uoa.gr NR 45 TC 120 Z9 133 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-623-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1088 BP 251 EP 264 DI 10.1196/annals.1366.032 PG 14 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Clinical Neurology SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BFU90 UT WOS:000244734200020 PM 17192571 ER PT S AU Thayer, JF Sternberg, E AF Thayer, Julian F. Sternberg, Esther BE Chrousos, GP Kaltsas, GA Mastorakos, G TI Beyond heart rate variability - Vagal regulation of allostatic systems SO NEUROENDOCRINE AND IMMUNE CROSSTALK SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 6th Meeting of the International-Society-for-Neuroimmunomodulation - Neuroendocrine and Immune Crosstalk CY SEP 25-28, 2005 CL Athens, GREECE SP Novartis, Ipsen PC DE heart rate variability; cortisol; glucose; inflammation; allostasis ID CARDIOVASCULAR-DISEASE; PREFRONTAL CORTEX; INHIBITORY CONTROL; RISK; ASSOCIATION; DEPRESSION; EMOTIONS; BEHAVIOR; AMYGDALA; ANXIETY AB The autonomic nervous system (ANS) plays a role in a wide range of somatic and mental diseases. Whereas the role of the ANS in the regulation of the cardiovascular system seems evident, its role in the regulation of other systems associated with allostasis is less clear. Using a model of neurovisceral integration we describe how the ANS and parasympathetic tone in particular may be associated with the regulation of allostatic systems associated with glucose regulation, hypothalamic-pituitary-adrenal (HPA) axis function, and inflammatory processes. Decreased vagal function and heart rate variability (HRV) were shown to be associated with increased fasting glucose and hemoglobin A1c levels, increased overnight urinary cortisol, and increased proinflammatory cytokines and acute-phase proteins. All of these factors have been associated with increased allostatic load and poor health. Thus, vagal activity appears to play an inhibitory function in the regulation of allostatic systems. The prefrontal cortex and the amygdala are important central nervous system structures linked to the regulation of these allostatic systems via the vagus nerve. Finally, the identification of this neurovisceral regulatory system may help to illuminate the pathway via which psychosocial factors may influence health and disease. C1 Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. NIH, Rockville, MD USA. RP Thayer, JF (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA. EM Thayer.39@osu.edu NR 56 TC 195 Z9 195 U1 4 U2 46 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-623-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1088 BP 361 EP 372 DI 10.1196/annals.1366.014 PG 12 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Clinical Neurology SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BFU90 UT WOS:000244734200029 PM 17192580 ER PT J AU Jensen, RT Rindi, G Arnold, R Lopes, JM Brandi, ML Bechstein, WO Christ, E Taal, BG Knigge, U Ahlman, H Kwekkeboom, DJ O'Toole, D AF Jensen, Robert T. Rindi, Guido Arnold, Rudolf Lopes, Jose M. Brandi, Maria Luisa Bechstein, Wolf O. Christ, Emanuel Taal, Babs G. Knigge, Ulrich Ahlman, Hakan Kwekkeboom, Dik J. O'Toole, Dermot TI Well-differentiated duodenal tumor/carcinoma (excluding gastrinomas) SO NEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st ENETS Consensus Conference on Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors CY NOV, 2005 CL Frascati, ITALY SP European Neuroendocrine Tumor Soc ID ZOLLINGER-ELLISON-SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ENDOCRINE GASTROENTEROPANCREATIC TUMORS; AMPULLARY CARCINOID-TUMORS; BONE METASTASES; ENDOSCOPIC ULTRASONOGRAPHY; NEUROENDOCRINE TUMORS; RADIONUCLIDE THERAPY; HORMONE CONTENT; GANGLIOCYTIC PARAGANGLIOMA C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Parma, Dipartimento Patol & Med Lab, I-43100 Parma, Italy. Univ Marburg, Div Gastroenterol & Endocrinol, Dept Internal Med, Marburg, Germany. IPATIMUP Hosp, Dept Pathol, Oporto, Portugal. Univ Florence, Dipartimento Fisiopatol Clin, Florence, Italy. Goethe Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany. Inselspital Bern, Dept Endocrinol, Bern, Switzerland. Netherlands Canc Ctr, Dept Oncol, Amsterdam, Netherlands. Rigshosp Blegdamsvej Hosp, Dept Surg, Copenhagen, Denmark. Univ Gothenburg, Dept Surg, Gothenburg, Sweden. Erasmus MC, Dept Nucl Med, Rotterdam, Netherlands. Hop Beaujon, Serv Gastroenterol Pancreatol Pole Maladies Appar, Clichy, France. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Lopes, Jose Manuel/J-7428-2013; scarpa, aldo/K-6832-2016; FALCHETTI, ALBERTO/Q-1787-2016; Christ, Emanuel/F-1196-2015; OI Perren, Aurel/0000-0002-6819-6092; Lopes, Jose Manuel/0000-0001-8597-3474; scarpa, aldo/0000-0003-1678-739X; FALCHETTI, ALBERTO/0000-0002-6739-4417; Christ, Emanuel/0000-0002-5604-4606; Falconi, Massimo/0000-0001-9654-7243; RINDI, Guido/0000-0003-2996-4404; OConnor, Juan Manuel/0000-0002-6975-5466 NR 93 TC 31 Z9 32 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 EI 1423-0194 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2006 VL 84 IS 3 BP 165 EP 172 DI 10.1159/000098008 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 140OR UT WOS:000244515600003 PM 17312376 ER PT J AU Jensen, RT Niederle, B Mitry, E Ramage, JK Steinmuller, T Lewington, V Scarpa, A Sundin, A Perren, A Gross, D O'Connor, JM Pauwels, S Kloppel, G AF Jensen, Robert T. Niederle, Bruno Mitry, Emmanuel Ramage, John K. Steinmueller, Thomas Lewington, V. Scarpa, Aldo Sundin, Anders Perren, Aurel Gross, David O'Connor, Juan M. Pauwels, Stanislas Kloeppel, Guenter TI Gastrinoma (duodenal and pancreatic) SO NEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st ENETS Consensus Conference on Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors CY NOV, 2005 CL Frascati, ITALY SP European Neuroendocrine Tumor Soc ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; LONG-TERM; NEUROENDOCRINE TUMORS; AGGRESSIVE RESECTION; LIVER METASTASES; NATURAL-HISTORY; GASTROENTEROPANCREATIC TUMORS; SURGICAL-MANAGEMENT C1 NIH, Digest Dis Branch, Bethesda, MD 20892 USA. Med Univ Vienna, Div Gen Surg, Dept Surg, Vienna, Austria. CHV A Pare Hosp, Dept Gastroenterol & Hepatol, Boulogne, France. Vivantes Humboldt Hosp, Dept Surg, Berlin, Germany. Royal Marsden Hosp, Dept Radiol, Sutton, Surrey, England. Univ Verona, Dept Pathol, I-37100 Verona, Italy. Uppsala Univ, Dept Radiol, Uppsala, Sweden. Univ Spital Zurich, Dept Pathol, Zurich, Switzerland. Hadassah Univ Hosp, Dept Endocrinol & Metab, IL-91120 Jerusalem, Israel. Alexander Fleming Inst, Dept Oncol, Buenos Aires, DF, Argentina. Catholic Univ Louvain, Lab Mol Imaging & Expt Radiotherapy, Brussels, Belgium. Univ Hosp Kiel, Dept Pathol, Kiel, Germany. RP Jensen, RT (reprint author), NIH, Digest Dis Branch, Bldg 10,Rom 9C-103, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Lopes, Jose Manuel/J-7428-2013; scarpa, aldo/K-6832-2016; FALCHETTI, ALBERTO/Q-1787-2016; OI Perren, Aurel/0000-0002-6819-6092; Lopes, Jose Manuel/0000-0001-8597-3474; scarpa, aldo/0000-0003-1678-739X; FALCHETTI, ALBERTO/0000-0002-6739-4417; Falconi, Massimo/0000-0001-9654-7243; RINDI, Guido/0000-0003-2996-4404; OConnor, Juan Manuel/0000-0002-6975-5466; Niederle, Bruno/0000-0001-8107-4068 NR 88 TC 117 Z9 126 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2006 VL 84 IS 3 BP 173 EP 182 DI 10.1159/000098009 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 140OR UT WOS:000244515600004 PM 17312377 ER PT J AU O'Toole, D Salazar, R Falconi, M Kaltsas, G Couvelard, A de Herder, WW Hyrdel, R Nikou, G Krenning, E Vullierme, MP Caplin, M Jensen, R Eriksson, B AF O'Toole, Dermot Salazar, Ramon Falconi, Massimo Kaltsas, Gregory Couvelard, Anne de Herder, Wouter W. Hyrdel, Rudolf Nikou, George Krenning, Eric Vullierme, Marie-Pierre Caplin, Martin Jensen, Robert Eriksson, Barbro TI Rare functioning pancreatic endocrine tumors SO NEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st ENETS Consensus Conference on Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors CY NOV, 2005 CL Frascati, ITALY SP European Neuroendocrine Tumor Soc ID METASTATIC NEUROENDOCRINE TUMORS; HEPATIC ARTERIAL CHEMOEMBOLIZATION; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; ZOLLINGER-ELLISON-SYNDROME; CARCINOID-TUMORS; GASTROENTEROPANCREATIC TUMORS; LIVER METASTASES; RADIOFREQUENCY ABLATION; GLUCAGONOMA SYNDROME; INTERFERON-ALPHA C1 Beaujon Hosp, Dept Gastroenterol, Clichy, France. Inst Catala Oncol, Dept Oncol, Barcelona, Spain. Univ Verona, Dept Surg, I-37100 Verona, Italy. Genimatas Hosp, Dept Endocrinol & Metab, Athens, Greece. Beaujon Hosp, Dept Gastroenterol, Clichy, France. Erasmus MC Univ, Dept Endocrinol, Rotterdam, Netherlands. Martin Univ, Dept Internal Med, Martin, Slovakia. Laiko Hosp, Dept Propaedeut Internal Med, Athens, Greece. Erasmus MC Univ, Dept Nucl Med, Rotterdam, Netherlands. Beaujon Hosp, Dept Gastroenterol, Clichy, France. Royal Free Hosp, Dept Gastroenterol, London NW3 2QG, England. NIH, Dept Cell Biol, Bethesda, MD 20892 USA. Univ Uppsala Hosp, Dept Endocrinol, Uppsala, Sweden. RP O'Toole, D (reprint author), CHU Angers, Dept Gastroenterol, F-49000 Angers, France. EM deotoole@chu-angers.fr RI Lopes, Jose Manuel/J-7428-2013; scarpa, aldo/K-6832-2016; FALCHETTI, ALBERTO/Q-1787-2016; OI Lopes, Jose Manuel/0000-0001-8597-3474; scarpa, aldo/0000-0003-1678-739X; FALCHETTI, ALBERTO/0000-0002-6739-4417; Falconi, Massimo/0000-0001-9654-7243; RINDI, Guido/0000-0003-2996-4404; OConnor, Juan Manuel/0000-0002-6975-5466; Perren, Aurel/0000-0002-6819-6092 NR 63 TC 68 Z9 69 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2006 VL 84 IS 3 BP 189 EP 195 DI 10.1159/000098011 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 140OR UT WOS:000244515600006 PM 17312379 ER PT J AU Chen, YJ Ojeaburu, JV Vortmeyer, A Zhuang, Z Jensen, RT AF Chen, YJ Ojeaburu, JV Vortmeyer, A Zhuang, Z Jensen, RT TI Alterations of chromosome 3p in gastrinomas: Correlation with tumoral and clinical prognostic features SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 3rd Annual Conference of the European-Neuroendocrine-Tumor-Society (ENETS) CY MAR 22-24, 2006 CL Prague, CZECH REPUBLIC SP European Neuroendocrine Tumor Soc C1 Chinese Acad Med Sci, Dept Gastroenterol, Peking Union Med Coll Hosp, Beijing 100037, Peoples R China. NIDDKD, Digest Dis Branch, Bethesda, MD 20892 USA. NINDS, Mol pathogenesis Unit, Surg Neurol Branch, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2006 VL 83 IS 1 MA B3 BP 54 EP 55 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 054DV UT WOS:000238357900069 ER PT J AU Boikos, SA Stratakis, CA AF Boikos, Sosipatros A. Stratakis, Constantine A. TI Carney complex: Pathology and molecular genetics SO NEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshop on Highlights in Basic and Clinical Neuroendocrinology CY NOV 04-05, 2005 CL Athens, GREECE DE Carney complex; multiple endocrine neoplasias; pituitary tumors; adrenal hyperplasia; Cushing syndrome; acromegaly ID PROTEIN-KINASE-A; PEUTZ-JEGHERS-SYNDROME; SUBUNIT TYPE 1A; REGULATORY SUBUNIT; INCREASED EXPRESSION; BINDING-PROTEINS; I-ALPHA; TUMORS; ENDOCRINE; PRKAR1A AB Carney complex (CNC) is a unique multiple endocrine neoplasia syndrome (MIM 160980) which is characterized by unusual biochemical features (chronic hype rsomatotropinemia and paradoxical responses of cortisol production to glucocorticoids) and multi-tissue involvement. The gene coding for the protein kinase A (PKA) type 1 alpha regulatory subunit, PRKAR1A, had been mapped to 17q22-24, one of the genetic loci involved in CNC, and allelic analysis using probes from this chromosomal region revealed consistent changes in CNC tumors. Sequencing of the PRKAR1A gene in over 100 kindreds showed a number of mutations; in almost all cases, the sequence change was predicted to lead to a premature stop codon, and mutant mRNAs were subject to nonsensemediated mRNA decay. In CNC cells, PKA activity assays showed increased stimulation by CAMP. Few mutations that did not lead to a premature stop codon have been described; they are also associated with increased PKA activity. PRKAR1A has been investigated in sporadic endocrine tumors; it does not appear to be mutated in pituitary adenomas, but both thyroid and adrenal neoplasms have been found to harbor somatic mutations of this gene. Animal models of the disease have been developed. CNC is the first human disease caused by mutations of one of the subunits of the PKA holoenzyme, a critical component of numerous cellular signaling systems. This has wide implications for CAMP involvement in endocrine tumorigenesis. Copyright (c) 2006 S. Karger AG, Basel C1 NICHHD, Sect Endocrinol & Genet, NIH, DEB, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, NIH, DEB, Bldg 10,CRC,Room I-3330, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 39 TC 47 Z9 48 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2006 VL 83 IS 3-4 BP 189 EP 199 DI 10.1159/000095527 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 095AH UT WOS:000241280100009 PM 17047382 ER PT J AU Espeland, MA Coker, LH Wallace, R Rapp, SR Resnick, SM Limacher, M Powell, LH Messina, CR AF Espeland, Mark A. Coker, Laura H. Wallace, Robert Rapp, Stephen R. Resnick, Susan M. Limacher, Marian Powell, Lynda H. Messina, Catherine R. CA Women's Hlth Initiative Study Co TI Association between alcohol intake and domain-specific cognitive function in older women SO NEUROEPIDEMIOLOGY LA English DT Article DE cognition; ethanol; women's health ID RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; ALZHEIMER-DISEASE; CONSUMPTION; ESTROGEN; PERFORMANCE; DEMENTIA; RISK; METAANALYSIS AB Moderate levels of alcohol intake may be associated with better cognitive function; however, this relationship may vary between cognitive domains. Women, aged 65-80 years, enrolled in the Women's Health Initiative (WHI) randomized clinical trials of hormone therapy, underwent annual standardized testing for global cognitive function through the ancillary WHI Memory Study (average follow-up of 4.5 years) and domain-specific cognitive function through the WHI Study of Cognitive Aging (average follow-up of 1.7 years). Compared to nondrinkers, women reporting moderate levels of alcohol intake (:53 drinks per day) performed better on a measure of global cognitive function. Women reporting any alcohol intake also performed better on tests of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, and motor speed (all p < 0.05), but not spatial ability (p = 0.36). After covariate adjustment, mean scores were higher among women reporting >= 1 drink/day by 5.7% for verbal knowledge (p < 0.001) and by 5.7% for phonemic fluency (p = 0.004), compared to never-drinkers. Moderate levels of alcohol intake are associated with somewhat better cognition, which may be expressed most strongly in functions related to verbal knowledge and phonemic fluency. However, our observational study cannot rule out confounding associations with unmeasured factors. Copyright (c) 2006 S. Karger AG, Basel C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Psychiat, Winston Salem, NC 27157 USA. Univ Iowa, Coll Med, Dept Epidemiol, Iowa City, IA USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Florida, Div Cardiovasc Med, Gainesville, FL 32611 USA. Rush Univ, Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA. RP Espeland, MA (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mespelan@wfubmc.edu FU NIA NIH HHS [N01-AG-1-2106] NR 47 TC 16 Z9 16 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2006 VL 27 IS 1 BP 1 EP 12 DI 10.1159/000093532 PG 12 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 066PX UT WOS:000239243700001 PM 16717476 ER PT J AU Launer, LJ Berger, K Breteler, MMB Dufouil, C Fuhrer, R Giampaoli, S Nilsson, LG Pajak, A de Ridder, M van Dijk, EJ Sans, S Schmidt, R Hofman, A AF Launer, LJ Berger, K Breteler, MMB Dufouil, C Fuhrer, R Giampaoli, S Nilsson, LG Pajak, A de Ridder, M van Dijk, EJ Sans, S Schmidt, R Hofman, A CA CASCADE Consortium TI Regional variability in the prevalence of cerebral white matter lesions: An MRI study in 9 European countries (CASCADE) SO NEUROEPIDEMIOLOGY LA English DT Article DE white matter lesion; epidemiology; cardiovascular; multicenter study ID CORONARY-HEART-DISEASE; CARDIOVASCULAR DETERMINANTS; MONICA PROJECT; ROTTERDAM SCAN; BLOOD-PRESSURE; DEMENTIA; HEALTH; STROKE; RISK; ABNORMALITIES AB White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions. Copyright (C) 2006 S. Karger AG, Basel. C1 NIA, Lab Epidemiol Demog Biometry, Bethesda, MD 20892 USA. Erasmus Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. Hop La Pitie Salpetriere, INSERM, Unit Epidemiol Res Neurol & Psychopathol 360, Paris, France. McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. Natl Ctr Epidemiol Surveillance & Hlth Promot, Ist Super Sanita, Rome, Italy. Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. Jagiellonian Univ, Sch Med, Inst Publ Hlth, Dept Epidemiol & Populat Studies, Krakow, Poland. Inst Hlth Studies, Barcelona, Spain. Karl Franzens Univ Graz, Dept Neurol, Graz, Austria. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Gateway Bldg,Room 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Dufouil, Carole/J-4968-2012; van Dijk, Ewoud/J-7951-2012; Breteler, Monique /J-5058-2014 NR 29 TC 39 Z9 45 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PY 2006 VL 26 IS 1 BP 23 EP 29 DI 10.1159/000089233 PG 7 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 987YW UT WOS:000233554800004 PM 16254450 ER PT J AU Brown, A George, D Fujita, M Liow, JS Ghose, S Sangare, J Hommer, A Innis, R AF Brown, Amira George, D. Fujita, M. Liow, J. S. Ghose, S. Sangare, J. Hommer, A. Innis, R. TI [11C]DASB imaging of serotonin transporters in alcoholic patients SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T166 EP T166 DI 10.1016/j.neuroimage.2006.04.149 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000147 ER PT J AU Brown, A George, D Fujita, M Liow, JS Ghose, S Sangare, J Hommer, D Innis, R AF Brown, Amira George, D. Fujita, M. Liow, J. -S. Ghose, S. Sangare, J. Hommer, D. Innis, R. TI PET [11C] DASB imaging of serotonin transporters in alcoholics with and without a history of aggression SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. South Western Univ, Dallas, TX USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T43 EP T43 DI 10.1016/j.neuroimage.2006.04.033 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000032 ER PT J AU Cai, LS Ye, D Liow, JS Hong, J Cohen, RM Pike, VW Innis, RB AF Cai, Lisheng Ye, D. Liow, J. -S. Hong, J. Cohen, R. M. Pike, V. W. Innis, R. B. TI PET imaging of transgenic mice TG2576 using the beta-amyloid radioligand, [C-11]PIB SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK DE Tg2576 mouse; beta-amyloid; radioligand; PET imaging; Alzheimer's disease C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIMH, Neuroimaging Sect, NIH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T141 EP T142 DI 10.1016/j.neuroimage.2006.04.125 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000123 ER PT J AU Cannon, DM Ichise, M Fromm, S Nugent, AC Rollis, D Gandhi, SK Klaver, JM Charney, DS Manji, HK Drevets, WC AF Cannon, Dara M. Ichise, M. Fromm, S. Nugent, A. C. Rollis, D. Gandhi, S. K. Klaver, J. M. Charney, D. S. Manji, H. K. Drevets, W. C. TI Serotonin transporter binding in major depressive disorder and bipolar disorder assessed using [11C]DASB and positron emission tomography SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK ID HUMAN BRAIN; EPISODES; PET C1 NIMH, Mood & Anxiety Disorders Program, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Div Nucl Med, Dept Radiol,Med Sch, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 6 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T42 EP T42 DI 10.1016/j.neuroimage.2006.04.032 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000031 ER PT J AU Carlson, P Bain, E Tinsley, R Nugent, A Carson, R Luckenbaugh, D Alesci, S Kling, M Gold, P Drevets, W AF Carlson, Paul Bain, E. Tinsley, R. Nugent, A. Carson, R. Luckenbaugh, D. Alesci, S. Kling, M. Gold, P. Drevets, W. TI Serotonin-1A receptor binding in depression: Correlates with interleukin-6 and the hypothalamic-pituitary-adrenal axis SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T173 EP T173 DI 10.1016/j.neuroimage.2006.04.156 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000154 ER PT J AU Chefer, S Kimes, A Domino, E London, E Mukhin, A AF Chefer, Svetlana Kimes, A. Domino, E. London, E. Mukhin, A. TI Estimation of D2-like dopamine receptor occupancy by dopamine in the MPTP primate model of Parkinson's disease SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIDA, IRP, Neuroimaging Res Branch, NIH DHHS, Baltimore, MD USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Pharmacol, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T144 EP T144 DI 10.1016/j.neuroimage.2006.04.127 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000125 ER PT J AU Chefer, S Le Foll, B Kimes, A Shumway, D Kurian, V Goldberg, SR Stein, E Mukhin, A AF Chefer, Svetlana Le Foll, B. Kimes, A. Shumway, D. Kurian, V. Goldberg, S. R. Stein, E. Mukhin, A. TI Quantification of alpha(4)beta(2)* nicotinic acetylcholine receptors (nAChRs) in squirrel monkey brain using PET and 2FA SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 DHHS, Behav Neurosci Res Branch, Preclin Pharmacol Sect, NIH, Baltimore, MD 21224 USA. DHHS, Neuroimaging Res Branch, NIDA IRP, NIH, Baltimore, MD 21224 USA. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T138 EP T138 DI 10.1016/j.neuroimage.2006.04.122 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000120 ER PT J AU Chefer, S Kimes, A Contoreggi, C Pavlova, O Stein, E Mukhin, A AF Chefer, Svetlana Kimes, Alane Contoreggi, Carlo Pavlova, Olga Stein, Elliot Mukhin, Alexey TI In vivo occupancy of alpha4beta2*nicotinic acetylcholine receptors (nAChRs) by nicotine: PET study with 2-[18F]FA in non-human primates and humans SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIDA, Neuroimaging Res Branch, IRP, DHHS,NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T25 EP T25 DI 10.1016/j.neuroimage.2006.04.015 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000014 ER PT J AU Donohue, S Halldin, C Finnema, S Gulyas, B Pike, V AF Donohue, Sean Halldin, C. Finnema, S. Gulyas, B. Pike, V. TI Synthesis and in vivo evaluation of a new PET radioligand for imaging the cannabinoid type-1 (CB1) receptors SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Bethesda, MD 20892 USA. Karolinska Inst, Karolinska Hosp, Dept Clin Neurosci, Psychiat & Psychol Sect, S-10401 Stockholm, Sweden. NR 0 TC 2 Z9 2 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T50 EP T50 DI 10.1016/j.neuroimage.2006.04.041 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000039 ER PT J AU Fujita, M Imaizumi, M D'Sa, C Zoghbi, SS Hong, J Musachio, JL Gee, AD Pike, VW Duman, RS Innis, RB AF Fujita, M. Imaizumi, M. D'Sa, C. Zoghbi, S. S. Hong, J. Musachio, J. L. Gee, A. D. Pike, V. W. Duman, R. S. Innis, R. B. TI In vivo and in vitro measurement of brain phosphodiesterase 4 in rats after antidepressant treatment SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. GlaxoSmithKline Inc, PET Div, Cambridge, England. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T143 EP T143 DI 10.1016/j.neuroimage.2006.04.126 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000124 ER PT J AU Ichise, M Cannon, D Klaver, JM Sangare, J Murphy, DL Innis, RB AF Ichise, Masanori Cannon, Dm Klaver, J. M. Sangare, J. Murphy, D. L. Innis, R. B. TI [11C]DASB PET imaging of serotonin transporters in unmedicated patients with early onset obsessive compulsive disorder SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NIMH, Program, NIH, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 3 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T167 EP T167 DI 10.1016/j.neuroimage.2006.04.150 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000148 ER PT J AU Imaizumi, M Briard, E Zoghbi, S Hong, J Shah, J Musachio, J Pike, V Innis, R Fujita, M AF Imaizumi, M. Briard, E. Zoghbi, S. Hong, J. Shah, J. Musachio, J. Pike, V. Innis, R. Fujita, M. TI Kinetic and metabolic evaluation of new PET ligands for peripheral benzodiazepine receptors SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T135 EP T135 DI 10.1016/j.neuroimage.2006.04.119 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000117 ER PT J AU Irnaizumi, M Zoghbi, S Hong, J Musachio, J Kim, HJ Chuang, DM Pike, V Innis, R Fujita, M AF Irnaizumi, M. Zoghbi, S. Hong, J. Musachio, J. Kim, H. J. Chuang, D. -M. Pike, V. Innis, Robert Fujita, M. TI PET imaging of cerebral ischemia with a peripheral benzodiazepine receptor ligand SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIMH, Mol Neurobiol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T35 EP T35 DI 10.1016/j.neuroimage.2006.04.025 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000024 ER PT J AU Kimes, AS Chefer, S Contoreggi, CS Hall, A Horti, A Vaupel, DB Pavlova, O Stein, EA Mukhin, AG AF Kimes, Alane S. Chefer, S. Contoreggi, C. S. Hall, A. Horti, A. Vaupel, D. B. Pavlova, O. Stein, E. A. Mukhin, A. G. TI In vivo quantification of the greater densities of alpha4beta2*nicotinic acetylcholine receptors in smokers compared to non-smokers SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIDA, IRP, NIH, DHHS, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RI Stein, Elliot/C-7349-2008 NR 0 TC 4 Z9 4 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T153 EP T153 DI 10.1016/j.neuroimage.2006.04.136 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000134 ER PT J AU Kimes, AS Chefer, S Contoreggi, CS Vaupel, DB Stein, EA Mukhin, AG AF Kimes, Alane S. Chefer, S. Contoreggi, C. S. Vaupel, D. B. Stein, E. A. Mukhin, A. G. TI Quantification of alpha4beta2*nicotinic acetylcholine receptors in human brain using bolus plus infusion administration of 2-[F-18]F-A-85380 SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIDA, IRP, DHHS, NIH, Baltimore, MD 21224 USA. RI Stein, Elliot/C-7349-2008 NR 0 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T102 EP T102 DI 10.1016/j.neuroimage.2006.04.089 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000087 ER PT J AU Liow, JS Lu, S McCarron, JA Hong, J Pike, VW Innis, RB Zoghbi, SS AF Liow, Jeih-San Lu, S. McCarron, J. A. Hong, J. Pike, V. W. Innis, R. B. Zoghbi, S. S. TI Effect of the P-gp modulator, cyclosporin-A, on the disposition of the 5-HT1A receptor radioligand [C-11](-)-RWAY in rodent brain and blood SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T129 EP T129 DI 10.1016/j.neuroimage.2006.04.113 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000111 ER PT J AU Schou, M Pike, VW Sovago, J Gulyas, B Gallagher, P Dobson, D Walter, MW Rudyk, H Farde, L Halldin, C AF Schou, Magnus Pike, V. W. Sovago, J. Gulyas, B. Gallagher, P. Dobson, D. Walter, M. W. Rudyk, H. Farde, L. Halldin, C. TI Synthesis of C-11-labeled (S,S)-CFMME and (R)-OHDMI and their evaluation as candidate radioligands for imaging norepinephrine transporters with PET SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 Karolinska Inst, Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, S-10401 Stockholm, Sweden. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Res Ctr Ltd, Windlesham GU20 6PH, Surrey, England. RI Sovago, Judit/G-7961-2011 NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T48 EP T48 DI 10.1016/j.neuroimage.2006.04.039 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000037 ER PT J AU Seneca, N Liow, JS Zoghbi, S Musachio, JL Hong, J Pike, VW Halldin, C Innis, RB AF Seneca, Nicholas Liow, J. S. Zoghbi, S. Musachio, J. L. Hong, J. Pike, V. W. Halldin, C. Innis, R. B. TI Imaging endogenous dopamine occupancy of the D2 receptor in rat brain with [11C]MNPA SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-10401 Stockholm, Sweden. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T119 EP T119 DI 10.1016/j.neuroimage.2006.04.105 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000103 ER PT J AU Seneca, N Gulyas, B Varrone, A Schou, M Tauscher, J Vandenhende, F Kielbasa, W Farde, L Innis, RB Halldin, C AF Seneca, Nicholas Gulyas, B. Varrone, A. Schou, M. Tauscher, J. Vandenhende, F. Kielbasa, W. Farde, L. Innis, R. B. Halldin, C. TI Atomoxetine occupies the norepinephrine transporter in a dose-dependent fashion: A PET study in nonhuman primate brain using (S,S)-[18F]FMeNER-D2 SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-10401 Stockholm, Sweden. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. CNR, Biostruct & Bioimaging Inst, Naples, Italy. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Lilly Res Labs, Mont St Guibert, Belgium. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T28 EP T28 DI 10.1016/j.neuroimage.2006.04.018 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000017 ER PT J AU Simeon, FG Brown, AK Patterson, VM Zoghbi, SS Innis, RB Pike, VW AF Simeon, Fabrice G. Brown, A. K. Patterson, V. M. Zoghbi, S. S. Innis, R. B. Pike, V. W. TI Labeling of a high affinity mGluR5 ligand with fluorine-18 in either of two positions for comparative evaluation as radioligands in monkey with PET SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIMH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T49 EP T49 DI 10.1016/j.neuroimage.2006.04.040 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000038 ER PT J AU Vaupel, DB Kunce, AL Stein, EA Mukhin, AG AF Vaupel, D. Bruce Kunce, A. L. Stein, E. A. Mukhin, A. G. TI Quantification of nicotinic receptors in the rat brain with microPET (R) and 2-[18F]F-A-85380 SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIDA, IRP, Baltimore, MD 21224 USA. RI Stein, Elliot/C-7349-2008 NR 0 TC 1 Z9 1 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T103 EP T103 DI 10.1016/j.neuroimage.2006.04.090 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000088 ER PT J AU Yasuno, F Zoghbi, S Julie, M Ichise, M Gladding, R Brown, A Bacher, J Pike, V Innis, R AF Yasuno, Fumihiko Zoghbi, S. Julie, Mc Ichise, M. Gladding, R. Brown, A. Bacher, J. Pike, V. Innis, R. TI Quantification of serotonin 5-HT1A receptors in monkey brain with [11C](-)-RWAY SO NEUROIMAGE LA English DT Meeting Abstract CT 6th International Symposium on Neuroreceptor Mapping CY JUL 06-08, 2006 CL Copenhagen, DENMARK C1 NIH, Vet Resources Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PY 2006 VL 31 SU 2 BP T98 EP T98 DI 10.1016/j.neuroimage.2006.04.085 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 060YC UT WOS:000238837000083 ER PT J AU Schaefer, M Noennig, N Heinze, HJ Rotte, M AF Schaefer, M Noennig, N Heinze, HJ Rotte, M TI Fooling your feelings: Artificially induced referred sensations are linked to a modulation of the primary somatosensory cortex SO NEUROIMAGE LA English DT Article DE referred sensation; touch; body image; somatosensory cortex; cross-modal; multisensory; magnetoencephalography ID INFLUENCES TACTILE PERCEPTION; UPPER EXTREMITY AMPUTEES; PHANTOM-LIMB PAIN; CORTICAL REORGANIZATION; TOOL USE; BODY; TOUCH; REPRESENTATION; PLASTICITY; BRAIN AB Recent studies demonstrated tactile illusions in healthy subjects by manipulating visual and tactile information. For example, a rubber hand, lying on a table in front of the subject and not connected with the body, can be felt by the subject as belonging to his or her own body by a simple visuotactile manipulation. Aim of the present study was to create an illusion in which the subject feels touch on a body site which is different from the actual touch, hence showing a referral of touch similar to those reported in phantom limb patients. Since it is known from animal studies that tactile illusions can alter early sensory processing, we were interested in the role of the primary somatosensory cortex (SI) during this kind of illusion. Thus, we manipulated the visual and tactile information in eight healthy subjects. The participants were stimulated on their fifth digit (D5) while watching a video, which showed a life-sized hand where the first digit (D1) was stimulated, hence inducing a conflict in feeling and seeing. The visual and tactile stimulation was in-phase in one condition and out-of-phase in a control condition. The video was presented in the peripersonal space of the subject at the distance where the real hand would be expected. Subjects reported a referred sensation of feeling the stimulation on D1 instead of D5 when the stimulation was in-phase with the video. Neuromagnetic source imaging of the topography of the functional organization of SI related to tactile stimulation of D1 and D5 showed that the source extent of the cortical representation of D5 increased during the illusion. The results suggest that a simple manipulation of visual and tactile information can induce referred sensations in healthy subjects in a very fast manner. Since the amount of the referred sensation was significantly correlated with the modulation in SI, we argue that SI is involved in this kind of artificially induced referred sensation. (c) 2005 Elsevier Inc. All rights reserved. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Otto Von Guericke Univ, Dept Neurol 2, D-39120 Magdeburg, Germany. RP Schaefer, M (reprint author), NINDS, Human Cort Physiol Sect, NIH, Bldg 10,Room 5S-208, Bethesda, MD 20892 USA. EM schaefem@ninds.nih.gov NR 38 TC 45 Z9 45 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2006 VL 29 IS 1 BP 67 EP 73 DI 10.1016/j.neuroimage.2005.07.001 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001ZO UT WOS:000234581400007 PM 16054839 ER PT J AU Rose, EJ Simonotto, E Ebmeier, KP AF Rose, EJ Simonotto, E Ebmeier, KP TI Limbic over-activity in depression during preserved performance on the n-back task SO NEUROIMAGE LA English DT Article; Proceedings Paper CT Annual Meeting of the Organization-for-Human-Brain-Mapping CY 2003 CL New York, NY SP Org Human Brain Mapping DE major depression; working memory; n-back; functional MRI; medial orbital prefrontal cortex; rostral anterior cingulate ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; SUBGENUAL PREFRONTAL CORTEX; UNIPOLAR MAJOR DEPRESSION; EMOTION-INDUCED CHANGES; WORKING-MEMORY; MOOD DISORDERS; NEUROPSYCHOLOGICAL FUNCTION; CLINICAL DEPRESSION; COGNITIVE-PROCESSES AB The profile of cognitive dysfunction observed in patients with major depressive disorder (MDD) may be partially attributed to a deficit in the central executive component of working memory (WM). This could be the consequence of a functional deficit in regions of cortex that are associated with WM function in healthy adults. In order to investigate this assertion, ten patients with a diagnosis of MDD and ten matched healthy controls undertook a parametric WM task (i.e. the n-back task) during the acquisition of blood oxygen level dependent echo planar magnetic resonance images (BOLD EPI fMRI). There was no significant difference in the behavioral performance of depressed patients and controls. This was true for both accuracy and reaction time on the aback task. Random effects analysis of the functional imaging data (using SPM99) revealed a significant difference in load-dependent activation in the medial orbitofrontal cortex/rostral anterior cingulate between patients and controls (cluster size (K-E)/volume = 128/1024 mm(3), P-(corrected) = 0.025). While both participant groups exhibited a significant decrease in activation in this region with increased task difficulty, the magnitude of this decrease was smaller in patients with MDD than in controls. Therefore, this study implies that the performance of WM tasks is associated with a dysfunctional activation of the medial orbitofrontal and rostral anterior cingulate cortex in MDD. The study thus offers a rationale for explaining depressive cognitive impairment by the abnormal fronto-limbic activation found in clinical depression. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Edinburgh, Sch Clin & Mol Med, Dept Psychiat, Div Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. Univ Edinburgh, SHEFC Brain Imaging Res Ctr Scotland, Edinburgh EH10 5HF, Midlothian, Scotland. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Ebmeier, KP (reprint author), Univ Edinburgh, Sch Clin & Mol Med, Dept Psychiat, Div Psychiat, Kennedy Tower,Morningside Pk, Edinburgh EH10 5HF, Midlothian, Scotland. EM k.ebmeier@ed.ac.uk RI Rose, Emma/A-9960-2010; OI Rose, Emma/0000-0001-5365-4794; Ebmeier, Klaus/0000-0002-5190-7038 NR 66 TC 67 Z9 67 U1 7 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2006 VL 29 IS 1 BP 203 EP 215 DI 10.1016/j.neuroimage.2005.07.002 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001ZO UT WOS:000234581400020 PM 16157491 ER PT J AU Mottaghy, FM Willmes, K Horwitz, B Muller, HW Krause, BJ Sturm, W AF Mottaghy, FM Willmes, K Horwitz, B Muller, HW Krause, BJ Sturm, W TI Systems level modeling of a neuronal network subserving intrinsic alertness SO NEUROIMAGE LA English DT Article ID ANTERIOR CINGULATE CORTEX; HEMISPHERIC CEREBRAL INFARCTION; SIMPLE REACTION-TIME; SUSTAINED ATTENTION; BLOOD-FLOW; FRONTAL LESIONS; HUMAN BRAIN; ACTIVATION; NEGLECT; TASK AB Cognitive control of alertness in unwarned situations (intrinsic alertness) relies on a predominantly right hemisphere cortical and subcortical network. In a previous functional activation study, we have demonstrated that this network comprises the anterior cingulate gyrus, the dorsolateral and polar frontal as well as the inferior parietal cortex, the thalamus and ponto-mesencephalic parts of the brain stem. The aim of this study was to study effective connectivity of this network by employing structural equation modeling. Fifteen right-handed male subjects participated in the PET study. The functional network showed stronger connectivity in the right hemisphere. Furthermore, there were strong effective connections between thalamus and brainstem on the one hand and between thalamus and anterior cingulate on the other. Our results suggest that the anterior cingulate functions as the central coordinating structure for the right hemispheric neural network of intrinsic alertness and that the anterior cingulate gyrus is modulated mainly by prefrontal and parietal cortex. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Hosp Ulm, Dept Nucl Med, D-89070 Ulm, Germany. HHU, Dept Nucl Med, Dusseldorf, Germany. KME, Res Ctr, Julich, Germany. RWTH Aachen Univ, Univ Hosp, Sect Neuropsychol, Neurol Clin, Aachen, Germany. NIDCD, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA. RP Krause, BJ (reprint author), Univ Hosp Ulm, Dept Nucl Med, Robert Koch Str 8, D-89070 Ulm, Germany. EM bernd-joachim.krause@medizin.uni-ulm.de RI Willmes, Klaus/A-1268-2014 OI Willmes, Klaus/0000-0002-9012-0553 NR 65 TC 55 Z9 55 U1 4 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2006 VL 29 IS 1 BP 225 EP 233 DI 10.1016/j.neuroimage.2005.07.034 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001ZO UT WOS:000234581400022 PM 16126415 ER PT J AU Volkow, ND Wang, GJ Franceschi, D Fowler, JS Thanos, PPK Maynard, L Gatley, SJ Wong, C Veech, RL Kunos, G Li, TK AF Volkow, ND Wang, GJ Franceschi, D Fowler, JS Thanos, PPK Maynard, L Gatley, SJ Wong, C Veech, RL Kunos, G Li, TK TI Low doses of alcohol substantially decrease glucose metabolism in the human brain SO NEUROIMAGE LA English DT Article ID CEREBRAL-BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; ETHANOL; RATS; ACETATE; INTOXICATION; ANESTHESIA; PET; CONSEQUENCES; ASTROCYTES AB Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that bloodborne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain. Published by Elsevier Inc. C1 NIDA, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Middlesettlement Family Practice, New Hartford, NY 13413 USA. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20850 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov FU Intramural NIH HHS; NIAAA NIH HHS [AA 09481] NR 40 TC 39 Z9 40 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2006 VL 29 IS 1 BP 295 EP 301 DI 10.1016/j.neuroimage.2005.07.004 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 001ZO UT WOS:000234581400029 PM 16085426 ER PT J AU Elenkov, IJ Chrousos, GP AF Elenkov, Ilia J. Chrousos, George P. TI Stress system - Organization, physiology and immunoregulation SO NEUROIMMUNOMODULATION LA English DT Article DE autoimmune diseases; cytokines; inflammation; Interleukins; stress; Th cells; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; SYMPATHETIC-NERVOUS-SYSTEM; MAST-CELL DEGRANULATION; RHEUMATOID-ARTHRITIS; INTERLEUKIN-10 PRODUCTION; IL-12 PRODUCTION; HUMAN MONOCYTES; IGE PRODUCTION; FACTOR-ALPHA; T-CELLS AB Stress is defined as a state of threatened homeostasis. The principal effectors of the stress system include corticotropin-releasing hormone, arginine vasopressin, the glucocorticoids, and the catecholamines norepinephrine and epinephrine. Activation of the stress system leads to adaptive behavioral and physical changes. The principal stress hormones glucocorticoids and catecholamines affect major immune functions such as antigen presentation, leukocyte proliferation and traffic, secretion of cytokines and antibodies, and selection of the T helper (Th) 1 versus Th2 responses. A fully fledged systemic inflammatory reaction results in stimulation of the stress response, which in turn, through induction of a Th2 shift protects the organism from systemic overshooting with Th1/pro- inflammatory cytokines. Stress is often regarded as immunosuppressive, but recent evidence indicates that stress hormones influence the immune response in a less monochromatic way-systemically they inhibit Th1/pro- inflammatory responses and induce a Th2 shift, whereas in certain local responses they promote pro-inflammatory cytokine production and activation of the corticotropin-releasing hormone-mast cell-histamine axis. Through this mechanism a hyper- or hypoactive stress system 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 chronic inflammation and immune-related diseases. Copyright (c) 2006 S. Karger AG, Basel. C1 NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Italian Natl Res Council, Inst Neurobiol & Mol Med, Rome, Italy. Univ Athens, Dept Pediat 1, Athens, Greece. RP Chrousos, GP (reprint author), NICHHD, NIH, Reprod Biol & Med Branch, Bldg 10,Room 1E-3140, Bethesda, MD 20892 USA. EM Chrousog@mail.nih.gov NR 71 TC 120 Z9 123 U1 2 U2 20 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2006 VL 13 IS 5-6 BP 257 EP 267 DI 10.1159/000104853 PG 11 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 203VM UT WOS:000249002100001 PM 17709947 ER PT J AU Xu, K Ernst, M Goldman, D AF Xu, K Ernst, M Goldman, D TI Imaging genomics applied to anxiety, stress response, and resiliency SO NEUROINFORMATICS LA English DT Review DE imaging genomics; anxiety; 5-HTT; COMT ID CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER GENE; PREFRONTAL CORTEX; MOOD DISORDERS; HUMAN BRAIN; PROMOTER POLYMORPHISM; PANIC DISORDER; WORKING-MEMORY; FUNCTIONAL PROMOTER; MALTREATED CHILDREN AB Anxiety and stress response/resiliency are heritable traits central to the etiology of multiple psychiatric diseases, but efforts to identify genetic variation influencing this broad domain of neurobiological function are hampered by the coarseness of the phenotypic measures and the effects of environmental factors. Neuroimaging offers a powerful approach for assessing functional neuronal activity. Neurophysiological measures can serve as intermediate phenotypes more directly linked to small gene effects, compared with behavioral end points of neural dysfunction. Imaging genomics is a relatively new research area that is concerned with linking functional gene variants and brain information processing. Here, we will focus on processes affected by anxiety and stress. Neuroimaging hits been combined with genetic analysis to reveal genetic effects of functional variants of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) genes on brain response to stressful stimuli. The low-expressing allele of the 5-HTT promoter polymorphism (HTTLPR) is associated with anxiety and with greater amygdala and other regional responses to emotional. The COMT Met158 allele leads to lower COMT activity and has also been associated with anxiety, and the effect of this gene is apparently additive with HTTLPR. Individuals with Met158 genotypes are more sensitive to pain stress and, as shown by C-11 Carfentanil imaging, have diminished ability to upregulate opioid release after pain/stress. These results suggest that functional variants of 5-HTT and COMT impact brain functions involved in stress and anxiety. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIMH, Sect Dev & Affect Neurosci MAP, NIH, Bethesda, MD 20892 USA. RP Xu, K (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32, Rockville, MD 20852 USA. EM ke@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 108 TC 27 Z9 30 U1 6 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 2006 VL 4 IS 1 BP 51 EP 64 DI 10.1385/NI:4:1:51 PG 14 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 015ER UT WOS:000235535200004 PM 16595858 ER PT J AU Huerta, MF Liu, Y Glanzman, DL AF Huerta, Michael F. Liu, Yuan Glanzman, Dennis L. TI A view of the digital landscape for neuroscience at NIH SO NEUROINFORMATICS LA English DT Editorial Material C1 NIMH, NIH, Bethesda, MD 20892 USA. NINDS, Off Int Activities, NIH, Bethesda, MD USA. NINDS, Computat Neurosci & Neuroinformat Program, NIH, Bethesda, MD USA. RP Huerta, MF (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. EM mnhuert1@mail.nih.gov NR 0 TC 6 Z9 6 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PY 2006 VL 4 IS 2 BP 131 EP 137 DI 10.1385/NI:4:2:131 PG 7 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 051DW UT WOS:000238142100002 PM 16845165 ER PT J AU Keator, DB Gadde, S Grethe, JS Taylor, DV Potkin, SG AF Keator, David Bryant Gadde, Syam Grethe, Jeffrey S. Taylor, Derek V. Potkin, Steven G. CA FIRST BIRN TI A general XML schema and SPM toolbox for storage of neuro-imaging results and anatomical labels SO NEUROINFORMATICS LA English DT Article ID SOFTWARE AB With the increased frequency of multisite, large-scale collaborative neuro-imaging studies, the need for a general, self-documenting framework for the storage and retrieval of activation maps and anatomical labels becomes evident. To address this need, we have developed and extensible markup language (XML) schema and associated tools for the storage of neuro-imaging activation maps and anatomical labels. This schema, as part of the XML-based Clinical Experiment Data Exchange (XCEDE) schema, provides storage capabilities for analysis annotations, activation threshold parameters, and cluster and voxel-level statistics. Activation parameters contain information describing the threshold, degrees of freedom, FWHM smoothness, search volumes, voxel sizes, expected voxels per cluster, and expected number of clusters in the statistical map. Cluster and voxel statistics can be stored along with the coordinates, threshold, and anatomical label information. Multiple threshold types can be documented for a given cluster or voxel along with the uncorrected and corrected probability values. Multiple atlases can be used to generate anatomical labels and stored for each significant voxel or cluter. Additionally, a toolbox for Statistical Parametric Mapping software (http://www.fil.ion.ucl.ac.uk/spm/) was created to capture the results from activation maps using the XML schema that supports both SPM99 and SPM2 versions (http://nbirn.net/Resources/Users/Applications/xcede/SPM_XMLTools.htm). Support for anatomical labeling is available via the Talairach Daemon (http://ric.uthscsa.edu/projects/talairachdaemon.html) and Automated Anatomical Labeling (http://www.cyceron.fr/freeware/). C1 Univ Calif Irvine, Irvine, CA 92697 USA. Duke Univ, Durham, NC USA. Univ Calif San Diego, La Jolla, CA 92093 USA. NCRR, NIH, Funct Imaging Res Schizophrenia Testbed, Biomed Informat Res Network, Bethesda, MD USA. RP Keator, DB (reprint author), Univ Calif Irvine, Irvine, CA 92697 USA. EM dbkeator@uci.edu RI Potkin, Steven/A-2021-2013; OI Potkin, Steven/0000-0003-1028-1013; Grethe, Jeffrey/0000-0001-5212-7052 FU NCRR NIH HHS [5 M01 RR 000827, 1 U24 RR019701-01] NR 10 TC 22 Z9 22 U1 2 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PY 2006 VL 4 IS 2 BP 199 EP 211 DI 10.1385/NI:4:2:199 PG 13 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 051DW UT WOS:000238142100006 PM 16845169 ER PT J AU Kernich, CA AF Kernich, CA TI Normal pressure hydrocephalus SO NEUROLOGIST LA English DT Article C1 Univ Hosp Hlth Syst, Univ Hosp Fac Serv, Dept Med, Cleveland, OH USA. RP Kernich, CA (reprint author), NINDS, POB 5801, Bethesda, MD 20824 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD JAN PY 2006 VL 12 IS 1 BP 57 EP 58 DI 10.1097/01.nrl.0000195829.16991.ef PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 004LJ UT WOS:000234754000008 PM 16547449 ER PT J AU Askanas, V Dalakas, MC Engel, WK AF Askanas, V Dalakas, MC Engel, WK TI Inclusion-body myositis - Clinical and pathologic aspects, and basic research potentially relevant to treatment SO NEUROLOGY LA English DT Editorial Material C1 Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90089 USA. NINDS, NIH, Neuoromuscular Dis Sect, Bethesda, MD 20892 USA. RP Askanas, V (reprint author), 637 S Lucas Ave, Los Angeles, CA 90017 USA. EM askanas@usc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2006 VL 66 SU 1 BP SI EP SI PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 005RX UT WOS:000234842600001 ER PT J AU Dalakas, MC AF Dalakas, MC TI Inflammatory, immune, and viral aspects of inclusion-body myositis SO NEUROLOGY LA English DT Article ID INFILTRATING T-CELLS; COSTIMULATORY MOLECULE; INTRAVENOUS IMMUNOGLOBULIN; MYOFIBRILLAR MYOPATHY; MUSCLE; EXPRESSION; POLYMYOSITIS; CHEMOKINES; DERMATOMYOSITIS; LYMPHOCYTES AB Muscle biopsies from patients with sporadic inclusion-body myositis (sIBM) consistently demonstrate that the inflammatory T cells almost invariably invade intact ( not vacuolated) fibers, whereas the vacuolated fibers are rarely invaded by T cells. This indicates two concurrently ongoing processes, an autoimmune mediated by cytotoxic T cells and a degenerative manifested by the vacuolated muscle fibers and deposits of amyloid-related proteins. The autoimmune features of IBM are highlighted by the strong association of the disease with: a) HLA I, II antigens, in frequency identical to classic autoimmune diseases; b) other autoimmune disorders in up to 32% of the patients, autoantibodies, paraproteinemias, or immunodeficiency; c) HIV and HTLV-I infection with increasingly recognized frequency (up to 13 known cases); and d) antigen-specific, cytotoxic, and clonally expanded CD8+ autoinvasive T cells with rearranged T-cell receptor genes that persist over time, even in different muscles, and invade muscle fibers expressing MHC-I antigen and costimulatory molecules. In contrast to IBM, in various dystrophies the inflammatory cells are clonally diverse and the muscle fibers do not express MHC-I or costimulatory molecules in the pattern seen in IBM. Like other chronic autoimmune conditions with coexisting inflammatory and degenerative features (i.e., primary progressive MS), IBM is resistant to conventional immunotherapies. Recent data suggest that strong anti-T cell therapies can be promising and they are the focus of ongoing research. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 49 TC 50 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2006 VL 66 SU 1 BP S33 EP S38 DI 10.1212/01.wnl.0000192129.65677.87 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 005RX UT WOS:000234842600006 PM 16432143 ER PT J AU Wang, Y Cheng, AW Mattson, MP AF Wang, Y Cheng, AW Mattson, MP TI The PTEN phosphatase is essential for long-term depression of hippocampal synapses SO NEUROMOLECULAR MEDICINE LA English DT Article DE calcium; long-term potentiation; learning and memory; PI3-kinase ID PAIRED-PULSE FACILITATION; LHERMITTE-DUCLOS-DISEASE; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; SYNAPTIC PLASTICITY; CA1 REGION; SOMA SIZE; POTENTIATION; MEMORY; LTP AB Activity-induced long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission are two types of enduring changes in neuronal connections that are believed to underlie learning and memory functions. Here we show that CA1 synapses in hippocampal slices from PTEN-deficient mice exhibit LTP, but are resistant to LTD. PTEN reduces phosphatidylinositol-3-kinase (PI3-K) activity, and pharmacological inhibition of PI3-K restores LTD in PTEN-deficient mice, suggesting that inhibition of PI3-K by PTEN is necessary for LTD induction. These findings demonstrate a pivotal role for PTEN in LTD, and suggest that alterations in PTEN could have an impact on learning and memory processes. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 26 TC 23 Z9 24 U1 0 U2 1 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 2006 VL 8 IS 3 BP 329 EP 335 DI 10.1385/NMM:8:3:329 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 053FG UT WOS:000238290400004 PM 16775384 ER PT J AU Liu, D Chan, SL de Souza-Pinto, NC Slevin, JR Wersto, RP Zhan, M Mustafa, K de Cabo, R Mattson, MP AF Liu, D Chan, SL de Souza-Pinto, NC Slevin, JR Wersto, RP Zhan, M Mustafa, K de Cabo, R Mattson, MP TI Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress SO NEUROMOLECULAR MEDICINE LA English DT Review DE caloric restriction; glucose transport; hippocampus; neuronal death; oxygen consumption ID OXYGEN SPECIES PRODUCTION; MESSENGER-RNA EXPRESSION; NMDA RECEPTOR ACTIVATION; CENTRAL-NERVOUS-SYSTEM; PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; UNCOUPLING PROTEIN-2; FATTY-ACIDS; CALORIC RESTRICTION; SKELETAL-MUSCLE AB The high-metabolic demand of neurons and their reliance on glucose as an energy source places them at risk for dysfunction and death under conditions of metabolic and oxidative stress. Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins implicated in the regulation of mitochondrial membrane potential (Delta psi(m)) and cellular energy metabolism. The authors cloned UCP4 cDNA from mouse and rat brain, and demonstrate that UCP4 mRNA is expressed abundantly in brain and at particularly high levels in populations of neurons believed to have high-energy requirements. Neural cells with increased levels of UCP4 exhibit decreased AV., reduced reactive oxygen species (ROS) production and decreased mitochondrial calcium accumulation. UCP4 expressing cells also exhibited changes of oxygen-consumption rate, GDP sensitivity, and response of Delta psi(m) to oligomycin that were consistent with mitochondrial uncoupling. UCP4 modulates neuronal energy metabolism by increasing glucose uptake and shifting the mode of ATP production from mitochondrial respiration to glycolysis, thereby maintaining cellular ATP levels. The UCP4-mediated shift in energy metabolism reduces ROS production and increases the resistance of neurons to oxidative and mitochondrial stress. Knockdown of UCP4 expression by RNA interference in primary hippocampal neurons results in mitochondrial calcium overload and cell death. UCP4-mRNA expression is increased in neurons exposed to cold temperatures and in brain cells of rats maintained on caloric restriction, suggesting a role for UCP4 in the previously reported antiageing and neuroprotective effects of caloric restriction. By shifting energy metabolism to reduce ROS production and cellular reliance on mitochondrial respiration, UCP4 can protect neurons against oxidative stress and calcium overload. C1 NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Lab Mol Gerontol, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Res Resources Branch, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Lab Expt Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Mattson, Mark/F-6038-2012; Souza-Pinto, Nadja/C-3462-2013; de Cabo, Rafael/J-5230-2016; OI Souza-Pinto, Nadja/0000-0003-4206-964X; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 117 TC 93 Z9 100 U1 1 U2 6 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 2006 VL 8 IS 3 BP 389 EP 413 DI 10.1385/NMM:8:3:389 PG 25 WC Neurosciences SC Neurosciences & Neurology GA 053FG UT WOS:000238290400010 PM 16775390 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Deciphering developmental CNS disorders SO NEUROMOLECULAR MEDICINE LA English DT Editorial Material C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 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 2006 VL 8 IS 4 BP 433 EP 434 DI 10.1385/NMM:8:4:433 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 110RW UT WOS:000242397700001 ER PT J AU Fields, RD AF Fields, RD TI Advances in understanding neuron-glia interactions SO NEURON GLIA BIOLOGY LA English DT Article DE neuron-glia interactions; synaptic plasticity; myelination; ischemia; calcium; pain; microglia; synaptogenesis AB Recent advances in the field of neuron-glia interactions were presented at the 27th International Symposium of the University of Montreal Center de Recherche en Sciences Neruologiques. Topics included synaptogenesis, regulation of synaptic strength by glia at the neuromuscular junction and hippocampus; myelin formation, structure, and maintenance; involvement of glia in nervous-system response to injury, hypoxia, and ischemia; neurogenesis and apoptosis, and microglial involvement in chronic pain. C1 NIH, Nervous Syst Dev & Plast Sect, NICHD, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NIH, Nervous Syst Dev & Plast Sect, NICHD, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov NR 20 TC 8 Z9 8 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2006 VL 2 BP 23 EP 26 DI 10.1017/S1740925X05000335 PN 1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 044UF UT WOS:000237697200004 PM 18634589 ER PT J AU Light, AR Wu, Y Hughen, RW Guthrie, PB AF Light, AR Wu, Y Hughen, RW Guthrie, PB TI Purinergic receptors activating rapid intracellular Ca2+ increases in microglia SO NEURON GLIA BIOLOGY LA English DT Article DE mouse; ATP receptors; glial cells; purines; pain; injury ID LONG-TERM HYPERALGESIA; SUBCUTANEOUS FORMALIN INJECTION; SPINAL GLIAL ACTIVATION; CENTRAL-NERVOUS-SYSTEM; ADULT-RAT BRAIN; CELLS IN-VITRO; EXTRACELLULAR ATP; CALCIUM WAVES; ADP RECEPTOR; P2Y RECEPTORS AB We provide both molecular and pharmacological evidence that the metabotropic, purinergic, P2Y(6), P2Y(12) and P2Y(13) receptors and the ionotropic P2X(4) receptor contribute strongly to the rapid calcium response caused by A TP and its analogues in mouse microglia. Real-time PCR demonstrates that the most prevalent P2 receptor in microglia is P2Y(6) followed, in order, by P2X(4), P2Y(12), and P2X(7) = P2Y(13). Only very small quantities of mRNA for P2Y(1), P2Y(2), P2Y(4), P2Y(14), P2X(3) and P2X(5) were found. Dose-response curves of the rapid calcium response gave a potency order of: 2MeSADP > ADP=UDP=IDP=UTP > ATP > BzATP, whereas A2P(4) had little effect. Pertussis toxin partially blocked responses to 2MeSADP, ADP and UDP. The P2X(4) antagonist suramin, lint not PPADS, significantly blocked responses to ATP. These data indicate that P2Y(6), P2Y(12), P2Y(13) and P2X receptors mediate much of the rapid calcium responses and shape changes in microglia to low concentrations of ATP, presumably at least partly because ATP is rapidly hydrolyzed to ADP. Expression of P2Y(6), P2Y(12) and P2Y(13) receptors appears to be largely glial in the brain, so that peripheral immune cells and CNS microglia share these receptors. Thus, purinergic, metabotropic, P2Y(6), P2Y(12), P2Y(13) and P2X(4) receptors might share a role in the activation and recruitment of microglia in the brain and spinal cord by widely varying stimuli that cause the release of ATP, including infection, injury and degeneration in the CNS, and peripheral tissue injury and inflammation which is signaled via nerve signaling to the spinal cord. C1 Univ Utah, Dept Anesthesiol, Salt Lake City, UT 84132 USA. Univ N Carolina, Sch Dent, Oral Biol Program, Chapel Hill, NC 27510 USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Light, AR (reprint author), Univ Utah, Dept Anesthesiol, 3C444 SOM,30N,1900 E, Salt Lake City, UT 84132 USA. EM alan.light@hsc.utah.edu FU NINDS NIH HHS [P01 NS039420-01A1, P01 NS039420, P01 NS039420-01A10001, P01 NS039420-01A19002, P01 NS039420-02, P01 NS039420-020001, P01 NS039420-029002, P01 NS039420-03, P01 NS039420-030001, P01 NS039420-039002, P01 NS039420-04, P01 NS039420-040001, P01 NS039420-049002, P01 NS039420-05, P01 NS039420-050001, P01 NS039420-059002] NR 75 TC 30 Z9 34 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1740-925X J9 NEURON GLIA BIOL JI Neuron Glia Biol. PY 2006 VL 2 BP 125 EP 138 DI 10.1017/S1740925X05000323 PN 2 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 041KN UT WOS:000237455200007 PM 16652167 ER PT J AU Lough, S Kipps, CM Treise, C Watson, P Blair, JR Hodges, JR AF Lough, S Kipps, CM Treise, C Watson, P Blair, JR Hodges, JR TI Social reasoning, emotion and empathy in frontotemporal dementia SO NEUROPSYCHOLOGIA LA English DT Article DE social cognition; frontotemporal dementia; theory of mind; emotion; empathy; executive function ID EXECUTIVE FUNCTIONS; ALZHEIMERS-DISEASE; AMYGDALA DAMAGE; MIND; SEVERITY; CRITERIA; DISSOCIATION; IMPAIRMENT; CONSENSUS; COGNITION AB Introduction: Social cognition is crucial for human interaction, and is markedly impaired in the frontal variant of frontotemporal dementia (fvFTD). The relationship of various aspects of social functioning, however, remains controversial in this group. Methods: Patients with fvFTD (n = 18), and matched controls (n = 13), were tested using tasks designed to assess their Theory of Mind (ToM), moral reasoning, emotion recognition and executive function. Caregivers documented changes in empathy compared to premorbid functioning. Results: We found marked impairments in the abilities of fvFTD patients, relative to controls, in ability to mentalise (ToM), which was evident on a cartoon test, but not on a story-based ToM task. Knowledge of social rules was intact, but moral reasoning was defective, and was due, in part, to an inability to rate the seriousness of moral and conventional transgressions appropriately. Executive function was impaired in this group, and compromised aspects of moral reasoning, but ToM performance was independent of this. Emotion recognition was globally impaired in fvFTD, but was particularly so for anger and disgust which may partly explain the difficulty these patients have with identifying social violations. Empathy, as rated by carers, was also shown to be abnormal. Conclusion: It appears that social reasoning is disrupted in a number of ways in fvFTD, and the findings provide a basis for the understanding and further study of abnormal behaviour in this disease. The results are discussed in light of neuroimaging findings in studies of social cognition and the locus of pathology in fvFTD. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Cambridge, Addenbrookes Hosp, Neurol Unit, Cambridge CB2 2QQ, England. Fulbourne Hosp, Dept Clin Psychol, Cambridge CB1 5EF, England. MRC, Cognit & Brain Sci Unit, Cambridge CB2 2EF, England. NIMH, Washington, DC 20032 USA. RP Hodges, JR (reprint author), Univ Cambridge, Addenbrookes Hosp, Neurol Unit, Cambridge CB2 2QQ, England. EM john.hodges@mrc-cbu.cam.ac.uk FU Medical Research Council [G9724461, MC_U105559861, MC_U105579212]; Wellcome Trust NR 46 TC 203 Z9 208 U1 2 U2 28 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 2006 VL 44 IS 6 BP 950 EP 958 DI 10.1016/j.neuropsychologia.2005.08.009 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 037UM UT WOS:000237172800011 PM 16198378 ER PT J AU Lotze, M Heymans, U Birbaumer, N Veit, R Erb, M Flor, H Halsband, U AF Lotze, M. Heymans, U. Birbaumer, N. Veit, R. Erb, M. Flor, H. Halsband, U. TI Differential cerebral activation during observation of expressive gestures and motor acts SO NEUROPSYCHOLOGIA LA English DT Article DE gesture; emotion; social interaction; mirror neurons; STS; BA 47 ID FACIAL EXPRESSIONS; OBJECT MANIPULATION; BIOLOGICAL MOTION; PREMOTOR CORTEX; IMITATION; FMRI; RECOGNITION; PERCEPTION; PARIETAL; MECHANISMS AB We compared brain activation involved in the observation of isolated right hand movements (e.g. twisting a lid), body-referred movements (e.g. brushing teeth) and expressive gestures (e.g. threatening) in 20 healthy subjects by using functional magnetic resonance imaging (MRI). Perception-related areas in the occipital and inferior temporal lobe but also the mirror neuron system in the lateral frontal (ventral premotor cortex and BA 44) and superior parietal lobe were active during all three conditions. Observation of body-referred compared to common hand actions induced increased activity in the bilateral posterior superior temporal sulcus (STS), the left temporo-parietal lobe and left BA 45. Expressive gestures involved additional areas related to social perception (bilateral STS, temporal poles, medial prefrontal lobe), emotional processing (bilateral amygdala, bilateral ventrolateral prefrontal cortex (VLPFC), speech and language processing (Broca's and Wernicke's areas) and the pre-supplementary motor area (pre-SMA). In comparison to body-referred actions, expressive gestures evoked additional activity only in the left VLPFC (BA 47). The valence-ratings for expressive gestures correlated significantly with activation intensity in the VLPFC during expressive gesture observation. Valence-ratings for negative expressive gestures correlated with right STS-activity. Our data suggest that both, the VLPFC and the STS are coding for differential emotional valence during the observation of expressive gestures. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Tubingen, Inst Med Psychol & Verhalstensneurobiol, D-72074 Tubingen, Germany. NINDS, NIH, Human Cortical Physiol Sect, Bethesda, MD 20892 USA. Univ Tubingen, Dept Neuroradiol, CNS, Sect Expt MR, Tubingen, Germany. Univ Heidelberg, Dept Clin & Cognit Neurosci, Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Univ Freiburg, Dept Psychol, Freiburg, Germany. RP Lotze, M (reprint author), Univ Tubingen, Inst Med Psychol & Verhalstensneurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM martin.lotze@uni-tuebingen.de RI Veit, Ralf/F-8907-2012; OI Veit, Ralf/0000-0001-9860-642X; Erb, Michael/0000-0002-9311-4693; Flor, Herta/0000-0003-4809-5398 NR 66 TC 79 Z9 79 U1 5 U2 19 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 2006 VL 44 IS 10 BP 1787 EP 1795 DI 10.1016/j.neuropsychologia.2006.03.016 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 068VS UT WOS:000239403200015 PM 16730755 ER PT J AU Vythilingam, M Lawley, M Collin, C Bonne, O Agarwal, R Hadd, K Charney, DS Grillon, C AF Vythilingam, M Lawley, M Collin, C Bonne, O Agarwal, R Hadd, K Charney, DS Grillon, C TI Hydrocortisone impairs hippocampal-dependent trace eyeblink conditioning in post-traumatic stress disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE post-traumatic stress disorder; trace eyeblink conditioning; glucocorticoid sensitivity; hippocampus ID NICTITATING-MEMBRANE RESPONSE; INHIBIT GLUCOSE-TRANSPORT; PLASMA-CORTISOL; DEXAMETHASONE SUPPRESSION; MOLECULAR MECHANISMS; COMBAT VETERANS; GLUCOCORTICOIDS; MEMORY; ACQUISITION; HORMONES AB Trace eyeblink conditioning is a hippocampal-dependent associative learning task that could help evaluate hippocampal function in Post-traumatic stress disorder (PTSD). Since preclinical research has demonstrated that trace eyeblink conditioning can be pharmacologically manipulated by glucocorticoids, this task may shed light on glucocorticoid sensitivity in PTSD. This study assessed baseline and hydrocortisone-mediated changes in trace eyeblink conditioning in patients with PTSD and in healthy controls. A total of 12 patients with PTSD and 12 age- and sex-matched healthy controls participated in a trace eyeblink test 6 h following intravenous administration of 30 mg of hydrocortisone. Spontaneous blink rates were similar between PTSD patients and healthy controls. There was no significant difference in the mean conditioned response between PTSD subjects and healthy controls under placebo conditions. Following hydrocortisone administration, only the PTSD patients demonstrated a significant reduction in conditioned response in contrast to healthy subjects who did not demonstrate any change. Patients with PTSD had increased glucocorticoid sensitivity in the focal brain regions mediating trace eyeblink conditioning. C1 NIMH, NIH, MAP, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Community Behav Hlth, Rockville, MD USA. Mt Sinai Sch Med, New York, NY USA. RP Vythilingam, M (reprint author), NIMH, NIH, MAP, Mood & Anxiety Disorders Program, 15K N Dr,Room 111,MSC 2670, Bethesda, MD 20892 USA. EM meena.vythi@nih.gov NR 48 TC 30 Z9 30 U1 3 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2006 VL 31 IS 1 BP 182 EP 188 DI 10.1038/sj.npp.1300843 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 023MX UT WOS:000236132000018 PM 16123770 ER PT J AU Tao-Cheng, JH AF Tao-Cheng, J-H. TI Activity-related redistribution of presynaptic proteins at the active zone SO NEUROSCIENCE LA English DT Article DE immunogold EM; RIM 1; synapsin 1; synuclein; Bassoon; Piccolo ID NEUROTRANSMITTER RELEASE; POSTSYNAPTIC DENSITY; SYNAPTIC PLASTICITY; ALPHA-SYNUCLEIN; VESICLES; CYTOMATRIX; RIM1-ALPHA; PICCOLO; SYNAPSES; MUNC13-1 AB Immunogold labeling distributions of seven presynaptic proteins were quantitatively analyzed under control conditions and after high K+ depolarization in excitatory synapses from dissociated rat hippocampal cultures. Three parallel zones in presynaptic terminals were sampled: zones I and II, each about one synaptic vesicle wide extending from the active zone; and zone III, containing a distal pool of vesicles up to 200 nm from the presynaptic membrane. The distributions of SV2 and synaptophysin, two synaptic vesicle integral membrane proteins, generally followed the distribution of synaptic vesicles, which were typically evenly distributed under control conditions and had a notable depletion in zone III after stimulation. Labels of synapsin I and synuclein, two synaptic vesicle-associated proteins, were similar to each other; both were particularly sparse in zone I under control conditions but showed a prominent enrichment toward the active zone, after stimulation. Labels of Bassoon, Piccolo and RIM 1, three active zone proteins, had very different distribution profiles from one another under control conditions. Bassoon was enriched in zone II, Piccolo and RIM 1 in zone I. After stimulation, Bassoon and Piccolo remained relatively unchanged, but RIM 1 redistributed with a significant decrease in zone I, and increases in zones II and III. These results demonstrate that Bassoon and Piccolo are stable components of the active zone while RIM 1, synapsin I and synuclein undergo dynamic redistribution with synaptic activity. Published by Elsevier Ltd on behalf of IBRO. C1 NINDS, Electron Microscopy Facil, NIH, Bethesda, MD USA. RP Tao-Cheng, JH (reprint author), NINDS, Electron Microscopy Facil, NIH, Bldg 49,Room 3A50, Bethesda, MD USA. EM chengs@ninds.nih.gov FU Intramural NIH HHS NR 33 TC 55 Z9 55 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 2006 VL 141 IS 3 BP 1217 EP 1224 DI 10.1016/j.neuroscience.2006.04.061 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 074OX UT WOS:000239822800012 PM 16757121 ER PT J AU Wang, J Swann, JM AF Wang, J. Swann, J. M. TI The magnocellular medial preoptic nucleus I. Sources of afferent input SO NEUROSCIENCE LA English DT Article DE preoptic; tract tracing; cholera toxin B; mating behavior; amygdala; hamster ID ANTERIOR HYPOTHALAMIC-LESIONS; SYRIAN-HAMSTER BRAIN; SEXUALLY DIMORPHIC NUCLEUS; CEREBRAL HEMISPHERE REGULATION; MESSENGER-RIBONUCLEIC-ACID; MALE REPRODUCTIVE-BEHAVIOR; MALE GOLDEN-HAMSTER; MALE SEX BEHAVIOR; STRIA TERMINALIS; MATING-BEHAVIOR AB The magnocellular medial preoptic nucleus plays a crucial role in the regulation of male sexual behavior in Syrian hamsters. Histological and behavioral studies suggest that the magnocellular medial preoptic nucleus regulates male mating behavior by integrating chemosensory and hormonal signals. The present study is the first to systematically identify the afferent connections of the magnocellular medial preoptic nucleus by tracing the uptake of cholera toxin B from deposits in the magnocellular medial preoptic nucleus of adult male Syrian hamsters. Our findings indicate that the magnocellular medial preoptic nucleus receives 1) chemosensory input from areas in the main and accessory olfactory pathways including the posterior medial bed nucleus of the stria terminalis, anterior medial, anterior cortical and posterior cortical nuclei of the amygdala; 2) input from steroid responsive structures such as the posterior medial nucleus of the amygdala, bed nucleus of the stria terminalis, lateral septum, anteroventral periventricular nucleus, medial preoptic nucleus, ventromedial nucleus of the hypothalamus and arcuate nucleus; 3) input from structures in the brainstem such as the subparafascicular thalamic nucleus, peripeduncular nucleus and the premamillary nucleus in the hypothalamus that carry sensory information from the genitalia. The major afferent input to the magnocellular medial preoptic nucleus was confirmed by injecting anterograde tracer bio-tinylated dextran amine into the anterior medical nucleus of the amygdala, the posterodorsal part of the medial nucleus of the amygdala, the posteromedial part of the bed nucleus of the stria terminalis and the posterointermediate part of the bed nucleus of the stria terminalis. Our results support the hypothesis that the magnocellular medial preoptic nucleus is part of the chemosensory pathway that receives chemosensory and hormonal input to regulate mating behavior and suggest that the magnocellular medial preoptic nucleus may utilize information from the genitalia to regulate male mating behavior. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA. NIMH, Genet Lab, Bethesda, MD 20892 USA. RP Swann, JM (reprint author), Lehigh Univ, Dept Biol Sci, 111 Res Dr, Bethlehem, PA 18015 USA. EM jms5@lehigh.edu OI Swann, Jennifer /0000-0001-8214-5972 NR 67 TC 10 Z9 10 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 2006 VL 141 IS 3 BP 1437 EP 1456 DI 10.1016/j.neuroscience.2006.04.079 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 074OX UT WOS:000239822800030 PM 16766128 ER PT J AU Zhao, S Edwards, J Carroll, J Wiedholz, L Millstein, RA Jaing, C Murphy, DL Lanthorn, TH Holmes, A AF Zhao, S Edwards, J Carroll, J Wiedholz, L Millstein, RA Jaing, C Murphy, DL Lanthorn, TH Holmes, A TI Insertion mutation at the C-terminus of serotonin transporter disrupts brain serotonin function and emotion-related in mice SO NEUROSCIENCE LA English DT Article DE serotonin transporter; 5-HTT; SERT; knockout; behavior; emotion ID ANXIETY-LIKE BEHAVIOR; EMBRYONIC STEM-CELLS; MAJOR DEPRESSION; DEFICIENT MICE; KNOCKOUT MICE; MUTANT MICE; GENE; MOUSE; RESPONSES; BINDING AB The 5-hydroxytryptamine transporter (5-HTT) regulates 5-hydroxytryptamine (5-HT) neurotransmission by removing 5-HT from the synaptic cleft. Emerging evidence from clinical and genetic studies implicates the 5-HTT in various neuropsychiatric conditions, including anxiety and depression. Here we report that a 5-HTT null mutant mouse line was generated by gene trapping that disrupted the sequence encoding the C-terminus of 5-HTT. This mutation resulted in significant reduction of 5-HTT mRNA and loss of 5-HTT protein. Brain levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were markedly decreased in C-terminus 5-HTT -/- mice, while 5-HT uptake or 5-HT content in platelets was absent. Behavioral phenotyping showed that C-terminus 5-HTT -/- mice were normal on a screen for gross behavioral, neurological, and sensory functions. In the tall suspension test for depression-related behavior, C-terminus 5-HTT -/- mice showed increased immobility relative to their +/+ controls. By comparison, a previously generated line of 5-HTT -/- mice lacking exon 2, encoding the N-terminus of the 5-HTT, showed abnormally high immobility in response to repeated, but not acute, exposure to the tail suspension test. In a novel, brightly-lit open field, both C-terminus 5-HTT -/- mice and N-terminus 5-HTT -/- mice displayed decreased center time and reduced locomotor activity compared with their +/+ controls. Both mutant lines buried significantly fewer marbles than their +/+ controls in the marble burying test. These findings further demonstrate the neurobiological functions of the 5-HTT and add to a growing literature linking genetic variation in 5-HTT function with emotional abnormalities. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Lexicon Gen Inc, The Woodlands, TX 77381 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Zhao, S (reprint author), Lexicon Gen Inc, 8800 Technol Forest Pl, The Woodlands, TX 77381 USA. EM szhao@lexgen.com FU Intramural NIH HHS NR 55 TC 53 Z9 56 U1 2 U2 9 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 2006 VL 140 IS 1 BP 321 EP 334 DI 10.1016/j.neuroscience.2006.01.049 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 047JC UT WOS:000237874600028 PM 16542782 ER PT J AU Eells, JB Misler, JA Nikodem, VM AF Eells, J. B. Misler, J. A. Nikodem, V. M. TI Early postnatal isolation reduces dopamine levels, elevates dopamine turnover and specifically disrupts prepulse inhibition in Nurr1-null heterozygous mice SO NEUROSCIENCE LA English DT Article DE NR4A2; isolation rearing; sensorimotor gating; catecholamine; schizophrenia ID MEDIAL PREFRONTAL CORTEX; ACOUSTIC STARTLE RESPONSE; RELEASE IN-VIVO; SCHIZOPHRENIC-PATIENTS; SEROTONERGIC FUNCTION; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; RATS; AMPHETAMINE; RECEPTORS AB Sensorimotor gating is a phenomenon that is linked with dopamine neurotransmission in limbic and cortical areas, and disruption of sensorimotor gating has been consistently demonstrated in schizophrenia patients. The nuclear receptor Nurr1 is essential for development of dopamine neurons and, using Nurr1-null heterozygous mice, has been found to be important for normal dopamine neurotransmission as null heterozygous mice have reduced limbic and cortical dopamine levels and elevated open-field locomotor activity. The current investigation compared sensorimotor gating, as measured by prepulse inhibition of the acoustic startle response, in Nurr1 wild-type and null heterozygous mice. When mice were weaned between 19 and 21 days of age either into isolation or groups of three to five and tested 12 weeks later, prepulse inhibition was elevated in group-raised null heterozygous mice and significantly disrupted in isolated null heterozygous mice as compared with isolation-raised wild-type mice and group-raised null heterozygous mice. Isolation had no effect on prepulse inhibition in wildtype mice. Isolation reduced tissue dopamine levels and elevated dopamine turnover in the nucleus accumbens and striatum in both wild-type and null heterozygous mice. In the prefrontal cortex, isolation reduced dopamine and 3,4-dihydroxyphenylacetic acid levels in null heterozygous as compared with isolation-raised wild-type mice, whereas no differences were observed between group-raised wild-type and null heterozygous mice. Neither the null heterozygous genotype nor isolation had any effect on basal or stress-induced corticosterone levels. These data suggest that the Nurr1 null heterozygous genotype predisposes these mice to isolation-induced disruption of prepulse inhibition that may be related to the interactions between intrinsic deficiencies in dopamine neurotransmission as a result of the null heterozygous genotype and isolation-induced changes in dopamine neurotransmission. Post-weaning isolation of Nurr1 null heterozygous mice provides a model to explore the interactions of genetic predisposition and environment/neurodevelopment on dopamine function that has important relevance to neuropsychiatric disorders. (c)' 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Eells, JB (reprint author), NIDDKD, NIH, 900 Rockville Pike, Bethesda, MD 20892 USA. EM eells@cvm.msstate.edu OI Eells, Jeffrey/0000-0002-6381-1666 FU Intramural NIH HHS NR 62 TC 37 Z9 38 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 2006 VL 140 IS 4 BP 1117 EP 1126 DI 10.1016/j.neuroscience.2005.12.065 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 063AB UT WOS:000238987100002 PM 16690213 ER PT J AU Windels, F Kiyatkin, EA AF Windels, F. Kiyatkin, E. A. TI Gabaergic mechanisms in regulating the activity state of substantia nigra pars reticulata neurons SO NEUROSCIENCE LA English DT Article DE basal ganglia; glutamate; autoactivity; bicuculline; nipecotic acid; gabazine ID GAMMA-AMINOBUTYRIC-ACID; UNRESTRAINED RATS; NEURAL ACTIVITY; BASAL GANGLIA; IN-VITRO; ELECTROPHYSIOLOGICAL PROPERTIES; NERVOUS-SYSTEM; GABA; DOPAMINE; AWAKE AB Substantia nigra reticulata is the major output structure of the basal ganglia involved in somatosensory integration and organization of movement. While previous work in vitro and in anesthetized animal preparations suggests that these neurons are autoactive and points to GABA as a primary input regulating their activity, single-unit recording coupled with iontophoresis was used in awake, unrestrained rats to further clarify the role of tonic and phasic GABA input in maintenance and fluctuations of substantia nigra reticulata neuronal activity under physiologically relevant conditions. In contrast to glutamate, which was virtually ineffective at stimulating substantia nigra reticulata neurons in awake rats, all substantia nigra reticulata neurons tested were inhibited by iontophoretic GABA and strongly excited by bicuculline, a GABA-A receptor blocker. The GABA-induced inhibition had short onset and offset latencies, a fading response pattern (a rapid decrease in rate followed by its relative restoration), and was independent of basal discharge rate. The bicuculline-induced excitation was inversely related to discharge rate and current (dose)-dependent in individual units. However, the average discharge rate during bicuculline applications at different currents increased to a similar plateau (similar to 60 impulses/s), which was about twice the mean basal rates. The excitatory effects of bicuculline were phasically inhibited or completely blocked by brief GABA applications and generally mimicked by gabazine, another selective GABA antagonist. These data as well as neuronal inhibitions induced by nipecotic acid, a selective GABA uptake inhibitor, suggest that substantia nigra reticulata neurons in awake, quietly resting conditions are under tonic, GABA-mediated inhibition. Therefore, because of inherent autoactivity and specifics of afferent inputs, substantia nigra reticulata neurons are very sensitive to phasic alterations in GABA input, which appears to be the primary factor determining fluctuations in their activity states under physiological conditions. While these cells are relatively insensitive to direct activation by glutamate, and resistant to a continuous increase in GABA input, they appear to be very sensitive to a diminished GABA input, which may release them from tonic inhibition and determine their functional hyperactivity. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov RI Windels, Francois/G-5432-2010 NR 45 TC 18 Z9 18 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 2006 VL 140 IS 4 BP 1289 EP 1299 DI 10.1016/j.neuroscience.2006.03.064 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 063AB UT WOS:000238987100018 PM 16713116 ER PT J AU Lepore, AC Neuhuber, B Connors, TM Han, SSW Liu, Y Daniels, MP Rao, MS Fischer, I AF Lepore, AC Neuhuber, B Connors, TM Han, SSW Liu, Y Daniels, MP Rao, MS Fischer, I TI Long-term fate of neural precursor cells following transplantation into developing and adult CNS SO NEUROSCIENCE LA English DT Article DE neural stem cells; neural progenitors; grafts; neurogenesis; NRP; GRP ID NEUROEPITHELIAL STEM-CELLS; GLIAL-RESTRICTED PRECURSORS; FORM FUNCTIONAL SYNAPSES; SPINAL-CORD-INJURY; DORSAL-ROOT AXONS; PARKINSONS-DISEASE; PROGENITOR CELLS; WHITE-MATTER; IN-VITRO; NEURONS AB Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can serve as an effective and safe replacement therapy for CNS injury and degeneration. (C) 2006 Published by Elsevier Ltd on behalf of IBRO. C1 Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fischer, I (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 2900 Queen Lane, Philadelphia, PA 19129 USA. EM ifischer@drexelmed.edu RI Fischer, Itzhak/D-1080-2012 OI Fischer, Itzhak/0000-0003-3187-8740 FU NINDS NIH HHS [NS 37515, NS24707] NR 44 TC 32 Z9 46 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 2006 VL 139 IS 2 BP 513 EP 530 DI 10.1016/j.neuroscience.2005.12.043 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 035CC UT WOS:000236976600010 PM 16458439 ER PT J AU Driscoll, I Howard, SR Stone, JC Monfils, MH Tomanek, B Brooks, WM Sutherland, RJ AF Driscoll, I Howard, SR Stone, JC Monfils, MH Tomanek, B Brooks, WM Sutherland, RJ TI The aging hippocampus: A multi-level analysis in the rat SO NEUROSCIENCE LA English DT Article DE FBNF1; Morris water task; transverse patterning; MRI; MRS; neurogenesis ID MAGNETIC-RESONANCE-SPECTROSCOPY; ACUTE BRAIN INJURY; L-ASPARTIC ACID; N-ACETYLASPARTATE; AGED RATS; NEURONAL LOSS; LESIONS; CORTEX; DAMAGE; NEUROGENESIS AB In the current experiment we conducted a multi-level analysis of age-related characteristics in the hippocampus of young adult (3 months), middle-aged (12 months), and old (24 months) Fisher 344 x Brown Norway hybrid (FBNF1) rats. We examined the relationships between aging, hippocampus, and memory using a combination of behavioral, non-invasive magnetic resonance imaging and spectroscopy, and postmortem neuroanatomical measures in the same rats. Aging was associated with functional deficits on hippocampus-dependent memory tasks, accompanied by structural alterations observed both in vivo (magnetic resonance imaging-hippocampal volume) and postmortem (dentate gyrus neuronal density and neurogenesis). Neuronal metabolic integrity, assessed by levels of N-acetylaspartate with magnetic resonance spectroscopy, was however, preserved. Further, our results suggest that neurogenesis (doublecortin) seems to be related to both performance deficits on hippocampus-dependent tasks and hippocampal volume reduction. The observed pattern of age-related alterations closely resembles that previously reported in humans and suggests FBNF1 rats to be a useful model of normal human aging. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIA, GEC, IRP, NIH, Baltimore, MD 21224 USA. Univ Lethbridge, Canadian Ctr Behav Neurosci, Lethbridge, AB T1K 3M4, Canada. Univ Calgary, Expt Imaging Ctr, Calgary, AB, Canada. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. RP Driscoll, I (reprint author), NIA, GEC, IRP, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM driscolli@mail.nih.gov RI Monfils, Marie/F-1282-2013; Tomanek, Boguslaw /J-4720-2014; OI Monfils, Marie-H./0000-0001-8971-6651; brooks, william/0000-0001-6227-7636 NR 40 TC 112 Z9 117 U1 0 U2 9 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 2006 VL 139 IS 4 BP 1173 EP 1185 DI 10.1016/j.neuroscience.2006.01.040 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 044SB UT WOS:000237691600002 PM 16564634 ER PT J AU Wang, J Palkovits, M Usdin, TB Dobolyi, A AF Wang, J Palkovits, M Usdin, TB Dobolyi, A TI Afferent connections of the subparafascicular area in rat SO NEUROSCIENCE LA English DT Article DE TIP39 immunocytochemistry; projection to the subparafascicular nucleus; periventricular gray of the posterior thalamus; retrograde tracer ID TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES; THALAMIC NUCLEUS; EFFERENT CONNECTIONS; HORSERADISH-PEROXIDASE; INFERIOR COLLICULUS; TEMPORAL CORTEX; MEDIAL THALAMUS; NERVOUS-SYSTEM; SPINAL-CORD AB The subparafascicular nucleus and the subparafascicular area are the major sites of synthesis of the recently discovered neuropeptide, tuberoinfundibular peptide of 39 residues (TIP39). Better knowledge of the neuronal inputs to the subparafascicular area and nucleus will facilitate investigation of the functions of TIP39. Thus, we have injected the retrograde tracer cholera toxin B subunit into the rostral, middle, and caudal parts of the rat subparafascicular nucleus. We report that the afferent projections to the subparafascicular nucleus and area include the medial prefrontal, insular, and ectorhinal cortex, the subiculum, the lateral septum, the anterior amygdaloid area, the medial amygdaloid nucleus, the caudal paralaminar area of the thalamus, the lateral preoptic area, the anterior, ventromedial, and posterior hypothalamic nuclei, the dorsal premamillary nucleus, the zona incerta and Forel's fields, the periaqueductal gray, the deep layers of the superior colliculus, cortical layers of the inferior colliculus, the cuneiform nucleus, the medial paralemniscal nucleus, and the parabrachial nuclei. Most of these regions project to all parts of the subparafascicular nucleus. However, the magnocellular subparafascicular neurons, which occupy the middle part of the subparafascicular nucleus, may not receive projections from the medial prefrontal and insular cortex, the medial amygdaloid nucleus, the lateral preoptic area, and the parabrachial nuclei. In addition, double labeling of cholera toxin B subunit and TIP39 revealed a remarkable similarity between input regions of the subparafascicular area and the brain TIP39 system. Neurons within regions that contain TIP39 cell bodies as well as regions that contain TIP39 fibers project to the subparafascicular area. Overall, the afferent connections of the subparafascicular nucleus and area suggest its involvement in central reproductive, visceral, nociceptive, and auditory regulation. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Genet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov RI Dobolyi, Arpad/B-9089-2008; Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Intramural NIH HHS NR 52 TC 19 Z9 19 U1 0 U2 3 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 2006 VL 138 IS 1 BP 197 EP 220 DI 10.1016/j.neuroscience.2005.11.010 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 020XU UT WOS:000235947400020 PM 16361065 ER PT J AU Wang, J Palkovits, M Usdin, TB Dobolyi, A AF Wang, J Palkovits, M Usdin, TB Dobolyi, A TI Forebrain projections of tuberoinfundibular peptide of 39 residues (TIP39)-containing subparafascicular neurons SO NEUROSCIENCE LA English DT Article DE immunohistochemistry; neuropeptide; tuberoinfundibular peptide of 39 residues; subparafascicular; neuroanatomical tract tracing; biotinylated dextran amine ID CATECHOLAMINE CELL GROUP; THALAMIC NUCLEUS; SPINAL-CORD; HORSERADISH-PEROXIDASE; ELECTRICAL-STIMULATION; PERIAQUEDUCTAL GRAY; AMYGDALOID COMPLEX; MEDIAL THALAMUS; NERVOUS-SYSTEM; BRAIN-STEM AB Neurons containing tuberoinfundibular peptide of 39 residues (TIP39) constitute a rostro-caudally elongated group of cells in the posterior thalamus. These neurons are located in the rostral part of the subparafascicular nucleus and in the subparafascicular area, caudally. Projections of the caudally located TIP39 neurons have been previously identified by their disappearance following lesions. We have now mapped the projections of the rat rostral subparafascicular neurons using injections of the anterograde tracer biotinylated dextran amine and the retrograde tracer cholera toxin B subunit, and confirmed the projections from more caudal areas previously inferred from lesion studies. Neurons from both the rostral subparafascicular nucleus and the subparafascicular area project to the medial prefrontal, insular, ecto- and perirhinal cortex, nucleus of the diagonal band, septum, central and basomedial amygdaloid nuclei, fundus striati, basal forebrain, midline and intralaminar thalamic nuclei, hypothalamus, subthalamus and the periaqueductal gray. The subparafascicular area projects more densely to the amygdala and the hypothalamus. In contrast, only the rostral part of the subparafascicular nucleus projects significantly to the superficial layers of prefrontal, insular, ecto-rhinal and somatosensory cortical areas. Double labeling showed that anterogradely labeled fibers from the rostral part of the subparafascicular nucleus contain TIP39 in many forebrain areas, but do not in hypothalamic areas. Injections of the retrograde tracer cholera toxin B subunit into the lateral septum and the fundus striati confirmed that they were indeed target regions of both the rostral subparafascicular nucleus and the subparafascicular area. In contrast, TIP39 neurons did not project to the anterior hypothalamic nucleus. Our data provide an anatomical basis for the potential involvement of rostral subparafascicular neurons in limbic and autonomic regulation, with TIP39 cells being major subparafascicular output neurons projecting to forebrain regions. (C) 2005 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Hungarian Acad Sci, H-1094 Budapest, Hungary. Semmelweis Univ, Neuromorphol Lab, H-1094 Budapest, Hungary. RP Usdin, TB (reprint author), NIMH, Genet Lab, Bldg 35,Room 1B215,35 Convent Dr, Bethesda, MD 20892 USA. EM usdint@mail.nih.gov RI Dobolyi, Arpad/B-9089-2008; Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU Intramural NIH HHS NR 61 TC 11 Z9 11 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 2006 VL 138 IS 4 BP 1245 EP 1263 DI 10.1016/j.neuroscience.2005.12.022 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 028QU UT WOS:000236504100020 PM 16458435 ER PT J AU Gehlbach, P Hose, S Lei, B Zhang, C Cano, M Arora, M Neal, R Barnstable, C Goldberg, MF Zigler, JS Sinha, D AF Gehlbach, P Hose, S Lei, B Zhang, C Cano, M Arora, M Neal, R Barnstable, C Goldberg, MF Zigler, JS Sinha, D TI Developmental abnormalities in the Nuc1 rat retina: A spontaneous mutation that affects neuronal and vscular remodeling and retinal function SO NEUROSCIENCE LA English DT Article DE retinal development; neurogenesis; vasculogenesis; gliosis; retinal function ID PROGRAMMED CELL-DEATH; VASCULAR DEVELOPMENT; MAMMALIAN RETINA; PROGENITOR CELLS; DEFICIENT MICE; VASCULOGENESIS; APOPTOSIS; MOUSE; EYE; BAX AB The retina serves as an excellent model in which to study vertebrate CNS development. We have discovered a spontaneous mutation in the Sprague-Dawley rat that results in a novel and unusual ocular phenotype, including retinal abnormalities, that we have named Nucl. We have previously shown that the Nucl mutation appears to suppress programmed cell death in the developing retina. Here we report that maturation of both the retinal neurons and the retinal vessels is abnormal in Nucl homozygous rats. The developmental changes in the retinal neurons and vasculature are correlated with regard to degree of abnormality. As Nucl homozygotes mature, focal retinal detachment begins at approximately 3 months after birth, and near total traction retinal detachment, associated with pre-retinal fibrosis and neovascularization, is evident by 18 months. Electroretinographic studies at 2.5 months of age indicate that functional retinal degeneration precedes retinal detachment. The functional abnormality is most evident in rods and the inner retina, and is present in homozygous but not heterozygous mutants. Immunocytochemical studies of rod and cone photoreceptors indicate abnormalities in rod, but not cone, photoreceptors in Nucl homozygotes, consistent with the electroretinographic findings. In Nucl animals, the Muller cells are activated. Although such activation may result from inflammation, Muller cells in Nucl may be reacting to a neuronal influence. It appears that the Nucl mutation plays a reg- C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. Univ Missouri, Dept Vet Med & Surg, Columbia, MO USA. NEI, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Ophthalmol & Neurobiol, New Haven, CT USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21287 USA. RP Sinha, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. EM Debasish@jhmi.edu FU NEI NIH HHS [KO8EY13420] NR 35 TC 14 Z9 14 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 2006 VL 137 IS 2 BP 447 EP 461 DI 10.1016/j.neuroscience.2005.08.084 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 007HM UT WOS:000234959600009 PM 16289888 ER PT J AU Ghitza, UE Prokopenko, VF West, MO Fabbricatore, AT AF Ghitza, UE Prokopenko, VF West, MO Fabbricatore, AT TI Higher magnitude accumbal phasic firing changes among core neurons exhibiting tonic firing increases during cocaine self-administration SO NEUROSCIENCE LA English DT Article DE addiction; electrophysiology; reward; motivation; conditioned; ventral striatum ID RAT NUCLEUS-ACCUMBENS; INTRAVENOUS COCAINE; SEEKING BEHAVIOR; VENTRAL STRIATUM; SPINY NEURONS; DOPAMINE; SHELL; ADDICTION; INHIBITION; RECEPTORS AB Studies using i.v. cocaine self-administration in rats have documented rapid-phasic changes in the firing rate of nucleus accumbens neurons within seconds of cocaine-reinforced lever presses, as well as changes that occur over the course of the cocaine self-administration experiment, i.e. tonic changes in firing rate. During the self-administration period of the experiment, individual neurons exhibit either a tonic increase, a tonic decrease, or no tonic change in firing rate, relative to the neuron's firing rate during the pre-drug period. We evaluated whether rapid-phasic changes in firing were differentially associated with tonically reduced or tonically elevated firing of nucleus accumbens core and shell neurons in cocaine self-administering rats. Rapid-phasic firing patterns within seconds of the coca i ne-rei nforced lever press were exhibited predominantly by core neurons that also exhibited tonic increases in firing. Conversely, core neurons that did not exhibit such rapid-phasic firing patterns were more likely to show tonically reduced firing. Moreover, core neurons were more likely than shell neurons to exhibit: 1) tonic increases in firing and 2) rapid-phasic increases in firing preceding the cocaine-reinforced lever press. These differences between accumbens subterritories may be related to their distinct involvement in operant responding; the present findings are consistent with an emerging literature which implicates shell in contextual stimulus-induced responding, and core in processing the instrumental response via its discrete output to classic basal ganglia structures. The distinct tendency of the core to exhibit increased firing, coupled with its dichotomous firing outputs (i.e. tonic decreases without rapid phasic responses or tonic increases with rapid phasic responses), may reflect particular sensitivity of these neurons to excitatory limbic afferent signaling involved in instrumental responding. Enhanced phasic responsivity in the core may be an integral component of the mechanism inherent in normal reward processing which is subverted by chronic drug exposure. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Res Branches, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA. RP Fabbricatore, AT (reprint author), NIDA, Behav Neurosci Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM tonio@rci.rutgers.edu FU NIDA NIH HHS [DA 06886] NR 61 TC 13 Z9 13 U1 3 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 2006 VL 137 IS 3 BP 1075 EP 1085 DI 10.1016/j.neuroscience.2005.10.026 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 009OG UT WOS:000235121000030 PM 16325346 ER PT J AU Kim, DS Palmiter, RD Cummins, A Gerfen, CR AF Kim, DS Palmiter, RD Cummins, A Gerfen, CR TI Reversal of supersensitive striatal dopamine D-1 receptor signaling and extracellular signal-regulated kinase activity in dopamine-deficient mice SO NEUROSCIENCE LA English DT Article DE dopamine receptor; L-DOPA; supersensitivity; extracellular receptor kinase; striatum; Parkinson's disease ID ELEMENT-BINDING PROTEIN; EARLY GENE INDUCTION; NERVE GROWTH-FACTOR; MAP KINASE; EXPRESSION; ERK; D1; ACTIVATION; CASCADE; STIMULATION AB Lesions of dopaminergic nigrostriatal neurons cause supersensitivity to dopamine in the striatum. Previous work has shown that such supersensitivity, an important aspect of rodent models of Parkinson's disease, is associated with anatomically abnormal patterns in the activation of extracellular signal-regulated kinase. After lesions of dopaminergic neurons, dopamine D-1-receptor agonists activate extracellular signal-regulated kinase in the dorsal striaturn, something not observed in intact animals. Here we used a more selective method of dopamine depletion. Dopamine-deficient mice, in which the tyrosine hydroxylase gene is specifically inactivated in dopaminergic neurons, were used to investigate dopamine D-1-receptor-mediated activation of extracellular signal-regulated kinase. In wild-type mice, acute treatment with a dopamine D,-receptor agonist results in activation of extracellular signal-regulated kinase in the nucleus accumbens without activation in the dorsal striaturn. In contrast, in dopamine-deficient mice, dopamine D-1-receptor-agonist treatment results in activation of extracellular signal-regulated kinase not only in the nucleus accumbens, but also throughout most of the dorsal striaturn. Chronic replacement of dopamine by repeated injection of L-DOPA for 36 h reverses this supersensitive extracellular signal-regulated kinase activation. This reversal displays a dorsal to ventral progression such that, by 36 h, extracellular signal-regulated kinase activation is virtually restricted to the nucleus accumbens, as in wild-type mice. The reversal of dopamine D-1-receptor activation of extracellular signal-regulated kinase in dopamine-deficient mice following chronic L-DOPA treatment shows that the lack of dopamine, rather than absence of other factors secreted from dopaminergic neurons, is responsible for dopamine supersensitivity. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Gerfen, CR (reprint author), NIMH, Lab Syst Neurosci, NIH, Bldg 35,Room 3A-1000,35 Convent Dr, Bethesda, MD 20892 USA. EM gerfenc@mail.nih.gov FU Intramural NIH HHS NR 28 TC 32 Z9 33 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 2006 VL 137 IS 4 BP 1381 EP 1388 DI 10.1016/j.neuroscience.2005.10.054 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 013JM UT WOS:000235405600026 PM 16388913 ER PT J AU Lenroot, RK Giedd, JN AF Lenroot, Rhoshel K. Giedd, Jay N. TI Brain development in children and adolescents: Insights from anatomical magnetic resonance imaging SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE brain; MRI; pediatric; development ID HUMAN CORPUS-CALLOSUM; HUMAN FRONTAL-CORTEX; FOOD-STORING BIRDS; SEXUAL DIMORPHISM; TEMPORAL-LOBE; MR-IMAGES; AGES 4-18; STATISTICAL APPROACH; WHITE-MATTER; SEGMENTATION AB Advances in neuroimaging have ushered in a new era of developmental neuroscience. Magnetic resonance imaging (MRI) is particularly well suited for pediatric studies because it does not use ionizing radiation which enables safe longitudinal scans of healthy children. Key findings related to brain anatomical changes during childhood and adolescent are increases in white matter volumes throughout the brain and regionally specific inverted U-shaped trajectories of gray matter volumes. Brain morphometric measures are highly variable across individuals and there is considerable overlap amongst groups of boys versus girls, typically developing versus neuropsychiatric populations, and young versus old. Studies are ongoing to explore the influences of genetic and environmental factors on developmental trajectories. (c) 2006 Published by Elsevier Ltd. C1 Natl Inst Mental Hlth, Child Psychiat Branch, Bethesda, MD 20854 USA. RP Giedd, JN (reprint author), Natl Inst Mental Hlth, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr, Bethesda, MD 20854 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 95 TC 577 Z9 600 U1 12 U2 95 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 2006 VL 30 IS 6 BP 718 EP 729 DI 10.1016/j.neubiorev.2006.06.001 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 093ZM UT WOS:000241208800002 PM 16887188 ER PT J AU Karl, A Schaefer, M Malta, LS Dorfel, D Rohleder, N Werner, A AF Karl, Anke Schaefer, Michael Malta, Loretta S. Doerfel, Denise Rohleder, Nicolas Werner, Annett TI A meta-analysis of structural brain abnormalities in PTSD SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE meta-analysis; PTSD; hippocampus; MRI; plasticity; memory ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; POSITRON-EMISSION-TOMOGRAPHY; SMALLER HIPPOCAMPAL VOLUME; VOXEL-BASED MORPHOMETRY; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW; PREFRONTAL CORTEX; VIETNAM VETERANS; TEMPORAL-LOBE AB This series of meta-analyses examined structural abnormalities of the hippocampus and other brain regions in persons with PTSD compared to trauma-exposed and non-exposed control groups. The findings were significantly smaller hippocampal volumes in persons with PTSD compared to controls with and without trauma exposure, but group differences were moderated by MRI methodology, PTSD severity, medication, age and gender. Trauma-exposed persons without PTSD also showed significantly smaller bilateral hippocampal compared to non-exposed controls. Meta-analyses also found significantly smaller left amygdala volumes in adults with PTSD compared to both healthy and trauma-exposed controls, and significantly smaller anterior cingulate cortex compared to trauma-exposed controls. Pediatric samples with PTSD exhibited significantly smaller corpus callosum and frontal lobe volumes compared to controls, but there were no group differences in hippocampal volume. The overall findings suggested a dimensional, developmental psychopathology systems model in which: (1) hippocampal volumetric differences covary with PTSD severity; (2) hippocampal volumetric differences do not become apparent until adulthood; and (3) PTSD is associated with abnormalities in multiple frontal-limbic system structures.. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Southampton, Sch Psychol, Southampton SO17 1BJ, Hants, England. Dresden Univ Technol, Biopsychol Unit, D-8027 Dresden, Germany. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Program Anxiety & Traumat Stress Studies, New York, NY 10021 USA. Dresden Univ Technol, Inst Radiol Diagnost, Univ Hosp, Dept Neuroradiol, D-01307 Dresden, Germany. RP Karl, A (reprint author), Univ Southampton, Sch Psychol, Southampton SO17 1BJ, Hants, England. EM karl@soton.ac.uk; Annett.Werner@uniklinikum-dresden.de RI Werner, 2509/C-4794-2013; Rohleder, Nicolas/N-7598-2013; OI Rohleder, Nicolas/0000-0003-2602-517X; Karl, Anke/0000-0002-6472-2876 NR 119 TC 354 Z9 363 U1 8 U2 36 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 2006 VL 30 IS 7 BP 1004 EP 1031 DI 10.1016/j.neubiorev.2006.03.004 PG 28 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 095KZ UT WOS:000241307900007 PM 16730374 ER PT J AU Andoh, T Chock, B Murphy, DL Chiueh, CC AF Andoh, Tsugunobu Chock, Boon Murphy, Dennis L. Chiueh, Chuang C. TI Involvement of thioredoxin on the neuroprotective effect of (-)-deprenyl SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 Toyama Univ, Dept Appl Pharmacol, Toyama 930, Japan. NHLBI, Biochem Lab, NIH, Bethesda, MD USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD USA. Taipei Med Univ, Taipei, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S58 EP S58 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609700312 ER PT J AU Araya, R Fukuda, T Kudoh, M Mishina, Y Yamada, M AF Araya, Runa Fukuda, T. Kudoh, Moeko Mishina, Yuji Yamada, Masahisa TI BMP signaling and cerebellar function SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama, Japan. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S112 EP S112 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609701136 ER PT J AU Hallett, M AF Hallett, Mark TI Abnormal cortical inhibition in dystonia SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S8 EP S8 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609700031 ER PT J AU Hirota, Y Ohshima, T Iwasato, T Kulkarni, AB Okano, H Sawamoto, K AF Hirota, Yuki Ohshima, Toshio Iwasato, Takuji Kulkarni, Ashok B. Okano, Hideyuki Sawamoto, Kazunobu TI cdk5 is required for neuroblast migration in the adult mouse brain SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 Keio Univ, Bridgestone Lab, Tokyo, Japan. Keio Univ, Dept Physiol, Tokyo, Japan. RIKEN, Tokyo, Japan. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S52 EP S52 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609700279 ER PT J AU Holmes, A AF Holmes, Andrew TI Mouse models of psychiatric disease SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S6 EP S6 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609700024 ER PT J AU Launey, T Li, CC Motoyama, Y Yamaoka, J Ito, M AF Launey, Thomas Li, Chou-Chi Motoyama, Yumiko Yamaoka, Junko Ito, Masao TI Regulation of AMPA receptor trafficking by AAA ATPases in cerebellar Purkinje cells: Are NSF and VCP playing complementary or antagonistic roles? SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 RIKEN, Brain Sci Inst, Wako, Saitama, Japan. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S207 EP S207 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609702176 ER PT J AU Matsuura, K Miura, K Taki, M Tabata, H Inaba, N Kawano, K Miles, FA AF Matsuura, Kiyoto Miura, Kenichiro Taki, Masakatsu Tabata, Hiromitsu Inaba, Naoko Kawano, Kenji Miles, Frederick A. TI The ocular following response (OFR) to moving grating patterns composed of two sinusoids in monkeys: Evidence or winner-take-all behavior SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 Kyoto Univ, Grad Sch Med, Kyoto, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S150 EP S150 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609701349 ER PT J AU Meyer-Lindenberg, A AF Meyer-Lindenberg, Andreas TI Neural mechanisms in Williams syndrome - Insights from neuroimaging SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S5 EP S5 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609700019 ER PT J AU Mizuhiki, T Richmond, BJ Shidara, M AF Mizuhiki, Takashi Richmond, Barry J. Shidara, Munetaka TI Anterior insular cortex neurons in monkey are activated when reward might be delivered, such as occurs in gambling SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 Univ Tsukuba, Grad Sch, Ibaraki, Japan. AIST, Tsukuba, Ibaraki, Japan. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S228 EP S228 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609702297 ER PT J AU Yamada, M Araya, R Kitamura, N Mishinsa, Y AF Yamada, Masahisa Araya, Runa Kitamura, Naoto Mishinsa, Yuji TI Autocrine BMP signaling in astroglia sensitizes the glial scarring SO NEUROSCIENCE RESEARCH LA English DT Meeting Abstract C1 RIKEN, BSI, Yamada Unit, Wako, Saitama, Japan. NIEH, NIHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PY 2006 VL 55 SU 1 BP S74 EP S74 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 057QG UT WOS:000238609700397 ER PT J AU Liu, ZG AF Liu, Z. G. TI The molecular mechanism of TNF signaling SO NEUROSIGNALS LA English DT Meeting Abstract CT Conference of the Croucher-Advanced-Study-Institute on Signaling in Cell Growth and Differentitation CY JAN, 2006 CL Hong Kong, PEOPLES R CHINA SP Hong Kong Univ Sci & Technol, Dept Biochem C1 NCI, Cell & Canc Biol BRanch, Ctr Canc Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-862X J9 NEUROSIGNALS JI Neurosignals PY 2006 VL 15 IS 1 MA 23 BP 46 EP 46 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences & Neurology GA 073DX UT WOS:000239724100027 ER PT J AU Kesavapany, S Pareek, TK Zheng, YL Amin, N Gutkind, JS Ma, W Kulkarni, AB Grant, P Pant, HC AF Kesavapany, Sashi Pareek, Tej Kumar Zheng, Ya-Li Amin, Niranjana Gutkind, J. Silvio Ma, Wu Kulkarni, Ashok B. Grant, Philip Pant, Harish C. TI Neuronal nuclear organization is controlled by cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor-1 SO NEUROSIGNALS LA English DT Article DE RasGRF1; p35; Cdk5; Ras; phosphorylation; nuclear organization ID ACTIVATED PROTEIN-KINASE; EXCHANGE FACTOR; CDK5 ACTIVITY; P35; CALCIUM; PATHWAY; EXPRESSION; GRF; RAS-GRF1/CDC25(MM); HIPPOCAMPUS AB RasGRF1 is a member of the Ras guanine nucleotide exchange factor ( RasGEF) family of proteins which are directly responsible for the activation of Ras and Rac GTPases. Originally identified as a phosphoprotein, RasGRF1 has been shown to be phosphorylated by protein kinase A and more recently, by the non-receptor tyrosine kinases Ack1 and Src. In this report we show that RasGRF1 interacts with and is phosphorylated by Cdk5 on serine 731 to regulate its steady state levels in mammalian cells as well as in neurons. Phosphorylation on this site by Cdk5 leads to RasGRF1 degradation through a calpain-dependent mechanism. Additionally, cortical neurons from Cdk5 knockout mice have higher levels of RasGRF1 which are reduced when wild-type Cdk5 is transfected into these neurons. In mitotic cells, nuclei become disorganized when RasGRF1 is overexpressed and this is rescued when RasGRF1 is co-expressed with active Cdk5. When RasGRF1 levels are elevated in neurons through overexpression of either the wild-type RasGRF1, or the phosphorylation mutant of RasGRF1 and by the transfection of a dominant negative Cdk5 construct, nuclei appeared condensed and fragmented. On the other hand, a reduction of RasGRF1 levels through p35/Cdk5 overexpression also leads to nuclear condensation in neurons. These data show that phosphorylation of RasGRF1 by Cdk5 tightly regulates its levels, which is essential for proper cellular organization. Copyright (c) 2006 S. Karger AG, Basel. C1 NIH, NINDS, Cytoskeletal Protein Regulat Sect, Bethesda, MD 20892 USA. NIH, Craniofacil Dev Biol & Regenerat Branch, Funct Genom Sect, Bethesda, MD 20892 USA. NIH, Natl Inst Dent & Craniofacial Res, Lab Oral & Pharryngeal Canc, Bethesda, MD 20892 USA. Ctr Biomol Sci & Engn, Naval Res Lab, Washington, DC USA. RP Pant, HC (reprint author), NIH, NINDS, Cytoskeletal Protein Regulat Sect, Bldg 49,Room 2A-35, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov RI Gutkind, J. Silvio/A-1053-2009; OI Pareek, Tej/0000-0001-5134-1647 NR 50 TC 9 Z9 14 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-862X J9 NEUROSIGNALS JI Neurosignals PY 2006 VL 15 IS 4 BP 157 EP 173 DI 10.1159/000095130 PG 17 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Cell Biology; Neurosciences & Neurology GA 178QV UT WOS:000247236100001 PM 16921254 ER PT J AU Lonser, RR Oldfield, EH AF Lonser, RR Oldfield, EH TI Spinal cord hemangioblastomas SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR GENE; SURGICAL-MANAGEMENT AB Spinal cord hemangioblastomas are histologically benign tumors that can cause significant morbidity because of their size, location, and associated edema or syrinx. They may be found sporadically or in association with von Hippel-Lindau disease (VHL). Spinal cord hemangioblastomas in these two settings (sporadic or in VHL) have different indications for surgical treatment and have variable follow-up paradigms. Generally, surgical resection of these tumors is curative and should be performed at the onset of symptoms in patients with VHL or for diagnostic and therapeutic purposes in sporadic cases. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov NR 17 TC 15 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 2006 VL 17 IS 1 BP 37 EP + DI 10.1016/j.nec.2005.10.005 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 013FI UT WOS:000235394800007 PM 16448906 ER PT J AU Braverman, AS Wess, J Ruggieri, MR AF Braverman, A. S. Wess, J. Ruggieri Sr., M. R. TI Organ and species differences in muscarinic receptor mediated smooth muscle contractile signal transduction. SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 36th Annual Meeting of the International-Continence-Society CY NOV 27-DEC 01, 2006 CL Christchurch, NEW ZEALAND SP Int Continence Soc C1 Temple Univ, Sch Med, Philadelphia, PA 19122 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RI Ruggieri, Michael/C-6262-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2006 VL 25 IS 6 SI SI MA 62 BP 584 EP 585 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 091QX UT WOS:000241044500063 ER PT J AU Di Marco, P Pagnotti, P Bellomi, F De Vito, G Sessal, E Bagnato, F Scagnolari, C Bramanti, P Antonelli, G AF Di Marco, P Pagnotti, P Bellomi, F De Vito, G Sessal, E Bagnato, F Scagnolari, C Bramanti, P Antonelli, G TI A novel assay to detect low-titred antibodies to interferon beta in multiple sclerosis patients SO NEW MICROBIOLOGICA LA English DT Article DE multiple sclerosis; interferon; interferon antibody ID CHRONIC HEPATITIS-C; NEUTRALIZING ANTIBODIES; MS PATIENTS; INHIBITORY-ACTIVITY; BIOAVAILABILITY; IFN; AUTOANTIBODIES; THERAPY; DISEASE AB Neutralizing antibodies (NAbs) may compromise interferon (IFN) clinical efficacy in patients with multiple sclerosis (MS) receiving IFN-beta treatment. When bioassays are used for anti-IFN-beta antibody detection, they are unable to discriminate between NAbs or other interfering substances with anti-IFN activity. Here we report the development of an anti-IFN-beta Western blot method that facilitates the detection of IFN low-titred antibodies and characterizes such low neutralizing activity as specifically due to the presence of particular IFN antibodies. The assay was characterized using serum samples from patients with MS treated with IFN-beta, It was developed by adding anti-IFN-positive antibody sera to Dynabeads M-280 tosylactivated followed by Western blot analysis. All sera samples from MS patients with IFN-betala NAbs (<= 50 t(1/10)) proved to be antibody-positive using this new method and, more importantly, four of 27 binding antibody-negative sera samples were scored as IFN antibody-positive. The method was found to be rapid, specific and sensitive and consistent with respect to well-established antiviral neutralization or commercial enzyme-linked immunosorbent assays. C1 Univ Roma La Sapienza, Dept Expt Med & Pathol, Virol Sect, I-00185 Rome, Italy. Univ Messina, Ctr Studi Neurolesi, Messina, Italy. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. RP Antonelli, G (reprint author), Univ Roma La Sapienza, Dept Expt Med & Pathol, Virol Sect, V Porta Tiburtina 28, I-00185 Rome, Italy. EM guido.antonelli@uniroma1.it RI SCAGNOLARI, CAROLINA/G-3837-2011 OI SCAGNOLARI, CAROLINA/0000-0003-1044-1478 NR 30 TC 1 Z9 1 U1 0 U2 1 PU EDIZIONI INTERNAZIONALI SRL PI PAVIA PA DIV EDIMES, EDIZIONI MEDICO SCIENTIFICHE PAVIA, VIA RIVIERA, PAVIA, 39-27100, ITALY SN 1121-7138 J9 NEW MICROBIOL JI New Microbiol. PD JAN PY 2006 VL 29 IS 1 BP 11 EP 18 PG 8 WC Microbiology SC Microbiology GA 028AL UT WOS:000236457600002 PM 16608120 ER PT S AU Habermann, JK Roblick, UJ Upender, M Ried, T Auer, G AF Habermann, Jens K. Roblick, Uwe J. Upender, Madhvi Ried, Thomas Auer, Gert BE LlombartBosch, A Felipo, V LopezGuerrero, JA TI From genome to proteome in tumor profiling: Molecular events in colorectal cancer genesis SO NEW TRENDS IN CANCER FOR THE 21ST CENTURY, 2ND EDITION SE Advances in Experimental Medicine and Biology LA English DT Proceedings Paper CT 2nd International Cancer Symposium on New Trends in Cancer for the 21st Century CY NOV 12-15, 2005 CL Valencia, SPAIN ID BRONCHIAL CELL ATYPIA; ULCERATIVE-COLITIS; GENETIC INSTABILITY; COLON-CANCER; CHROMOSOMAL INSTABILITY; EXPRESSION PATTERNS; INDUCED ANEUPLOIDY; MASS-SPECTROMETRY; MYELOID-LEUKEMIA; DNA ANEUPLOIDY AB Biomedical research has advanced rapidly in recent years with the sequencing of the human genome and the availability of technologies such as global gene and protein expression profiling using different chip platforms. However, this progress has not yet been transferred to the bedside. While detection of cancer at early stages is critical for curative treatment interventions, efficient diagnostic and therapeutic markers for the majority of malignancies still seem to be lacking. Comprehensive tumor profiling has therefore become a field of intensive research aiming at identifying biomarkers relevant for improved diagnostics and therapeutics. This chapter will demonstrate a genomic and proteomic approach while focusing on tumor profiling during colorectal cancer development. C1 [Habermann, Jens K.; Roblick, Uwe J.] Univ Hosp Schleswig Holstein, Dept Surg, Surg Res Lab, Campus Lubeck, Lubeck, Germany. [Habermann, Jens K.; Upender, Madhvi; Ried, Thomas] NIH, Natl Canc Inst, Dept Genet, Bethesda, MD 20892 USA. [Roblick, Uwe J.; Auer, Gert] Karolinska Univ, Hosp Solna, Canc Ctr Karolinska, Unit Canc Proteom, Stockholm, Sweden. RP Habermann, JK (reprint author), Univ Hosp Schleswig Holstein, Dept Surg, Surg Res Lab, Campus Lubeck, Lubeck, Germany. NR 73 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 1-4020-4966-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 587 BP 161 EP + PG 6 WC Oncology SC Oncology GA BFN31 UT WOS:000243248800015 PM 17163165 ER PT S AU Roberts, A Subbarao, K AF Roberts, Anjeanette Subbarao, Kanta BE Perlamn, S Holmes, KV TI Animal models for SARS SO NIDOVIRUSES: TOWARD CONTROL OF SARS AND OTHER NIDOVIRUS DISEASES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 10th International Nidovirus Symposium CY JUN 25-30, 2005 CL Colorado Springs, CO ID ACUTE RESPIRATORY SYNDROME; SYNDROME-ASSOCIATED CORONAVIRUS; HUMAN MONOCLONAL-ANTIBODY; GOLDEN SYRIAN-HAMSTERS; NEUTRALIZING ANTIBODY; PROTECTIVE IMMUNITY; INFECTION; MICE; VIRUS; IMMUNOPROPHYLAXIS C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Roberts, A (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 25 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 0-387-26202-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 581 BP 463 EP 471 PG 9 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Virology SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Virology GA BFC74 UT WOS:000241010800083 PM 17037579 ER PT J AU Moustapha, ME Ehrhardt, GJ Smith, CJ Szajek, LP Eckelman, WC Jurisson, SS AF Moustapha, ME Ehrhardt, GJ Smith, CJ Szajek, LP Eckelman, WC Jurisson, SS TI Preparation of cyclotron-produced Re-186 and comparison with reactor-produced Re-186 and generator-produced Re-188 for the labeling of bombesin SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE NCA Re-186; CA Re-186; NCA Re-188; cyclotron production; reactor production; Re-186,Re-188-labeled bombesin ID CARRIER-ADDED RE-186; RADIOPHARMACEUTICALS AB The radioisotopes Re-186 and Re-188 have been extensively investigated for various forms of radiotherapy due to their useful and high-abundance particle emissions, low-abundance and imageable gamma-rays, and chemical resemblance to technetium. In addition. Re-188 is available in no-carrier-added (NCA) form from long lived W-188 generators, whereas Re-186 can be produced in large quantities from reactors, although not in NCA form. However NCA Re-186 can be produced on a cyclotron by a (p,n) reaction on W-186. The purpose of this Study was to compare labeling of the peptide bombesin with these three forms of rhenium radioisotopes. Cyclotron-produced NCA Re-186 was separated radiochemically from enriched W-186 (96.9%) targets using high-purity methyl ethyl ketone (MEK). The resulting Re-186-MEK was then loaded onto a small alumina column to separate he resulting NCA Re-186 from any remaining W-186. The experimental levels of impurities associated with Re-186 at the end of the separation process were found to be 5.7 x 10(-6) Ci of Re-182 (0.57%, t(1/2) = 12.7 h) and 1.283 x 10(-5) Ci of Re-182m (1.28%, t(1/2) = 2.67 days). The radionuclidic purity of the separated Re-186 was found to be 99.6%, whereas the chemical identity was determined by reversed phase high-perforniance liquid chromatography (RP-HPLC) to be perrhenate ((ReO4-)-Re-186). Generator-produced (ReO4-)-Re-188 from a W-188/Re-188 generator (Oak Ridge National Laboratory) and CA (ReO4-)-Re-186 produced from a Re-185(n,gamma)Re-186 reaction at the University of Missouri Research Reactor (MURR) were used for comparison with the NCA Re-186 in subsequent studies. N3S-5-Ava-BBN(7-14)NH2 conjugates provide flexibility for designing Re-186,Re-188-labeled conjugates that retain high in vitro and in vivo specificity targeting of GRP receptor-expressing cells. This study showed that the N3S-5-Ava-BBN(7-14)NH2 could be labeled with Re-186,Re-188 following the preconjugation, postmetallation approach. The (ReO)-Re-186,188-O-V-N3S-5-Ava-BBN(7-14)NH2 complexes were found to form stable complexes following the reduction of perrhenate ((ReO4-)-O-VII) with stannous chloride at room temperature, as verified by HPLC and stability studies. The radiolabeling yield was found to be > 90%. The HPLC chromatograms of Re-186,Re-188-N3S-5-Ava-BBN(7-14)NH2 complexes revealed two peaks for each conjugate, reflecting the presence of syn- and anti-isomers, which were resolvable by HPLC but re-isomerized on separation. The biodistribution studies showed that the compounds were excreted through the renal and hepatobiliary systems and demonstrated receptor-specific uptake with an average pancreas accumulation of 8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked pancreatic uptake and further reflects the high specificity this conjugate has for the GRP receptors. At low levels of radioactivity. radiolysis effects were not observed. Scale-LIP may or may not elicit this effect, particularly for the higher energy beta emitter Re-188. The biodistribution studies demonstrated that the CA and NCA Re-186,Re-188 conjugates behaved similarly, raising the question of whether NCA Re-186,Re-188 is necessary for specific tumor receptor targeting. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Missouri, Dept Chem, Columbia, MO 65211 USA. Univ Missouri, Dept Radiol, Columbia, MO 65211 USA. Univ Missouri, MURR, Columbia, MO 65211 USA. Harry S Truman Mem Vet Hosp, Res Serv, Columbia, MO 65201 USA. NIH, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. RP Jurisson, SS (reprint author), Univ Missouri, Dept Chem, Columbia, MO 65211 USA. EM jurissons@missouri.edu NR 19 TC 33 Z9 34 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2006 VL 33 IS 1 BP 81 EP 89 DI 10.1016/j.nucmedbio.2005.09.006 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 017FV UT WOS:000235680400012 PM 16459262 ER PT J AU Mamede, M Carrasquillo, JA Chen, CC Del Corral, P Whatley, M Ilias, I Ayala, A Pacak, K AF Mamede, M Carrasquillo, JA Chen, CC Del Corral, P Whatley, M Ilias, I Ayala, A Pacak, K TI Discordant localization of 2-[F-18]-fluoro-2-deoxy-D-glucose in 6-[F-18]-fluorodopamine- and [I-123]-metaiodobenzylguanidine-negative metastatic pheochromocytoma sites SO NUCLEAR MEDICINE COMMUNICATIONS LA English DT Article DE fluorodeoxyglucose; fluorodopamine; pheochromocytoma; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; PET; DIAGNOSIS; FDG; PARAGANGLIOMA; SCINTIGRAPHY AB Background Although the majority of pheochromocytomas (PHEO) are benign, a subset is malignant. Computed tomography (CT) and magnetic resonance imaging (MRI) localize PHEO with high sensitivity but, because of limited specificity, [I-131]- or [I-123]-metaiodobenzylguanidine ([I-131]- or [I-123]-MIBG) is often used as a complementary agent. 6-[F-18]-fluorodopamine ([F-18]-DA) has been developed as a radiopharmaceutical for the targeting of noradrenergic pathways, and has been shown to result in a better detection rate of PHEO sites than MIBG; however, [F-18]-DA has shown a lack of accumulation in some patients with metastatic PHEO. Methods Five patients with widespread metastatic PHEO who had CT and MRI evidence of metastatic disease (one man and four women; age range, 25-64 years), and who underwent imaging with [I-123]-MIBG, [F-18]-DA and 2[F-18]-fluoro-2-deoxy-D-glucose ([F-18]-FDG), were evaluated retrospectively. Tomographic imaging was performed and positron emission tomography (PET) images were inspected visually and quantitatively. Results All five patients had [I-123]-MIBG scans that grossly underestimated the extent of disease when compared with conventional CT and MRI. All lesions seen on [I-123]-MIBG scans were detected on [F-18]-DA scans, which also detected additional lesions. Nonetheless, [F-18]-DA also failed to detect numerous lesions seen on CT and MRI. In all of these cases, [F-18]-FDG PET showed lesions that were not detected on either [I-123]-MIBG or [F-18]-DA scans. Conclusions When [I-123]-MIBG or [F-18]-DA fails to localize lesions seen on conventional imaging studies, [F-18]-FDG may be recommended as an ancillary test for the diagnosis and localization of metastatic PHEO. This is particularly important in patients with aggressive PHEC. C1 NICHHD, Reprod Biol & Med Branch, CRC, NIH, Bethesda, MD 20892 USA. NICHHD, Dept Nucl Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Reprod Biol & Med Branch, CRC, NIH, Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; Mamede, Marcelo/A-1751-2014; OI Mamede, Marcelo/0000-0001-5818-0954; Carrasquillo, Jorge/0000-0002-8513-5734 NR 31 TC 56 Z9 58 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0143-3636 J9 NUCL MED COMMUN JI Nucl. Med. Commun. PD JAN PY 2006 VL 27 IS 1 BP 31 EP 36 DI 10.1097/01.mnm.0000189780.54658.e8 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 000WX UT WOS:000234494200006 PM 16340721 ER PT S AU Ng, L Forrest, D AF Ng, Lily Forrest, Douglas BE Taneja, R TI Developmental roles of the thyroid hormone receptor alpha and beta genes SO NUCLEAR RECEPTORS IN DEVELOPMENT SE Advances in Developmental Biology LA English DT Article; Book Chapter ID TYPE-2 IODOTHYRONINE DEIODINASE; THYROTROPIN-RELEASING-HORMONE; NEONATAL-RAT-BRAIN; DOMINANT-NEGATIVE MUTATION; DEVELOPING MOUSE RETINA; HEARING-LOSS; POSTNATAL-DEVELOPMENT; CONE PHOTORECEPTORS; MESSENGER-RNAS; XENOPUS-LAEVIS C1 [Ng, Lily; Forrest, Douglas] NIDDKD, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Ng, L (reprint author), NIDDKD, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. NR 163 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1574-3349 BN 978-0-08-046940-9; 978-0-444-52873-5 J9 AD DEV BIOL PY 2006 VL 16 BP 1 EP 31 DI 10.1016/S1574-3349(06)16001-9 PG 31 WC Developmental Biology SC Developmental Biology GA BCQ80 UT WOS:000311041700002 ER PT S AU Jetten, AM Joo, JH AF Jetten, Anton M. Joo, Joung Hyuck BE Taneja, R TI Retinoid-related orphan receptors (RORs): Roles in cellular differentiation and development SO NUCLEAR RECEPTORS IN DEVELOPMENT SE Advances in Developmental Biology LA English DT Article; Book Chapter ID STAGGERER MUTANT MOUSE; LYMPHOID ORGAN DEVELOPMENT; NUCLEAR HORMONE-RECEPTORS; LIGAND-BINDING DOMAIN; MAMMALIAN CIRCADIAN CLOCK; CEREBELLAR PURKINJE-CELL; REV-ERB-ALPHA; PROTEASOME-MEDIATED DEGRADATION; DOUBLE-POSITIVE THYMOCYTES; LYMPHOTOXIN BETA-RECEPTOR C1 [Jetten, Anton M.; Joo, Joung Hyuck] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 FU Intramural NIH HHS [Z01 ES101586-05] NR 241 TC 35 Z9 36 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 978-0-08-046940-9 J9 AD DEV BIOL PY 2006 VL 16 BP 313 EP 355 DI 10.1016/S1574-3349(06)16010-X PG 43 WC Developmental Biology SC Developmental Biology GA BCQ80 UT WOS:000311041700011 PM 18418469 ER PT J AU Bogerd, HP Wiegand, HL Doehle, BP Lueders, KK Cullen, BR AF Bogerd, HP Wiegand, HL Doehle, BP Lueders, KK Cullen, BR TI APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN ENDOGENOUS RETROVIRUS; CYTIDINE DEAMINASES; HIV-1 VIRIONS; ANTIRETROVIRAL DEFENSE; VIRUS-REPLICATION; HUMAN TISSUES; IN-VIVO; DNA; PROTEIN; VIF AB While the ability of APOBEC3G to reduce the replication of a range of exogenous retroviruses is now well established, recent evidence has suggested that APOBEC3G can also inhibit the replication of endogenous retrotransposons that bear long terminal repeats. Here, we extend this earlier work by showing that two other members of the human APOBEC3 protein family, APOBEC3B and APOBEC3A, can reduce retrotransposition by the intracisternal A-particle (IAP) retrotransposon in human cells by 20-fold to up to 100-fold, respectively. This compares to an similar to 4-fold inhibition in IAP retrotransposition induced by APOBEC3G. While both APOBEC3G and APOBEC3B specifically interact with the IAP Gag protein in co-expressing cells, and induce extensive editing of IAP reverse transcripts, APOBEC3A fails to package detectably into IAP virus-like particles and does not edit IAP reverse transcripts. These data, which identify human APOBEC3A as a highly potent inhibitor of LTR-retrotransposon function, are the first to ascribe a biological activity to APOBEC3A. Moreover, these results argue that APOBEC3A inhibits IAP retrotransposition via a novel mechanism that is distinct from, and in this case more effective than, the DNA editing mechanism characteristic of APOBEC3G and APOBEC3B. C1 Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20895 USA. RP Cullen, BR (reprint author), Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA. EM culle002@mc.duke.edu FU NIAID NIH HHS [AI057099, AI065301, AI65301, R01 AI057099, R01 AI065301] NR 41 TC 178 Z9 180 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 2006 VL 34 IS 1 BP 89 EP 95 DI 10.1093/nar/gkj416 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 004WC UT WOS:000234782300016 PM 16407327 ER PT J AU Muftuoglu, M Sharma, S Thorslund, T Stevnsner, T Soerensen, MM Brosh, RM Bohr, VA AF Muftuoglu, M Sharma, S Thorslund, T Stevnsner, T Soerensen, MM Brosh, RM Bohr, VA TI Cockayne syndrome group B protein has novel strand annealing and exchange activities SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION-COUPLED REPAIR; SISTER-CHROMATID-EXCHANGE; DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; FACTOR CSB/ERCC6; HELICASE DOMAIN; ATPASE DOMAIN; GENE-PRODUCT; CSB PROTEIN AB Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by UV sensitivity, severe neurological abnormalities and prageroid symptoms. The CS complementation group B (CSB) protein is involved in UV-induced transcription coupled repair (TCR), base excision repair and general transcription. CSB also has a DNA-dependent ATPase activity that may play a role in remodeling chromatin in vivo. This study reports the novel finding that CSB catalyzes the annealing of complementary single-stranded DNA (ssDNA) molecules with high efficiency, and has strand exchange activity. The rate of CSB-catalyzed annealing of complementary ssDNA is 25-fold faster than the rate of spontaneous ssDNA annealing under identical in vitro conditions and the reaction occurs with a high specificity in the presence of excess non-homologous ssDNA. The specificity and intrinsic nature of the reaction is also confirmed by the observation that it is stimulated by dephosphorylation of CSB, which occurs after UV-induced DNA damage, and is inhibited in the presence of ATP gamma S. Potential roles of CSB in cooperation with strand annealing and exchange activities for TCR and homologous recombination are discussed. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Aarhus, Danish Ctr Mol Gerontol, Dept Mol Biol, Aarhus, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Sharma, Sudha/0000-0003-2765-2482 NR 34 TC 28 Z9 29 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 2006 VL 34 IS 1 BP 295 EP 304 DI 10.1093/nar/gkj410 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 004WC UT WOS:000234782300035 PM 16410611 ER PT J AU Fisher, RJ Fivash, MJ Stephen, AG Hagan, NA Shenoy, SR Medaglia, MV Smith, LR Worthy, KM Simpson, JT Shoemaker, R McNitt, KL Johnson, DG Hixson, CV Gorelick, RJ Fabris, D Henderson, LE Rein, A AF Fisher, RJ Fivash, MJ Stephen, AG Hagan, NA Shenoy, SR Medaglia, MV Smith, LR Worthy, KM Simpson, JT Shoemaker, R McNitt, KL Johnson, DG Hixson, CV Gorelick, RJ Fabris, D Henderson, LE Rein, A TI Complex interactions of HIV-1 nucleocapsid protein with oligonucleotides SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEIC-ACID-CHAPERONE; REPRESSOR-OPERATOR INTERACTION; DIFFUSION-DRIVEN MECHANISMS; PRIMER BINDING-SITE; ZINC-FINGER STRUCTURES; GENOMIC RNA; IN-VITRO; REVERSE TRANSCRIPTION; RECOGNITION ELEMENT AB The HIV-1 nucleocapsid (NC) protein is a small, basic protein containing two retroviral zinc fingers. It is a highly active nucleic acid chaperone; because of this activity, it plays a crucial role in virus replication as a cofactor during reverse transcription, and is probably important in other steps of the replication cycle as well. We previously reported that NC binds with high-affinity to the repeating sequence d(TG)(n). We have now analyzed the interaction between NC and d(TG)(4) in considerable detail, using surface plasmon resonance (SPR), tryptophan fluorescence quenching (TFQ), fluorescence anisotropy (FA), isothermal titration calorimetry (ITC) and electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). Our results show that the interactions between these two molecules are surprisngly complex: while the K-d for binding of a single d(TG)(4) molecule to NC is only similar to 5 nM in 150 mM NaCl, a single NC molecule is capable of interacting with more than one d(TG)(4) molecule, and conversely, more than one NC molecule can bind to a single d(TG)(4) molecule. The strengths of these additional binding reactions are quantitated. The implications of this multivalency for the functions of NC in virus replication are discussed. C1 NCI, Prot Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Data Management Serv Inc, Frederick, MD 21702 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. NCI, Mol Targets Dev Program, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Fisher, RJ (reprint author), NCI, Prot Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. EM fisher@ncifcrf.gov RI Fisher, Robert/B-1431-2009 FU Intramural NIH HHS; NCI NIH HHS [N01-CO12400, N01-CO12401, N01CO12400, N02CO12401]; NIGMS NIH HHS [R01-GM643208, 1T32-GM066706, T32 GM066706] NR 41 TC 68 Z9 69 U1 1 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. PY 2006 VL 34 IS 2 BP 472 EP 484 DI 10.1093/nar/gkj442 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 011TO UT WOS:000235291300018 PM 16434700 ER PT J AU Lobanov, AV Delgado, C Rahlfs, S Novoselov, SV Kryukov, GV Gromer, S Hatfield, DL Becker, K Gladyshev, VN AF Lobanov, AV Delgado, C Rahlfs, S Novoselov, SV Kryukov, GV Gromer, S Hatfield, DL Becker, K Gladyshev, VN TI The Plasmodium selenoproteome SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SELENOCYSTEINE TRANSFER-RNA; GENOME SEQUENCE; CHLAMYDOMONAS-REINHARDTII; EUKARYOTIC SELENOPROTEIN; GLUTATHIONE-PEROXIDASE; INSERTION; FALCIPARUM; SELENIUM; ELEMENT; IDENTIFICATION AB The use of selenocysteine (Sec) as the 21st amino acid in the genetic code has been described in all three major domains of life. However, within eukaryotes, selenoproteins are only known in animals and algae. In this study, we characterized selenoproteomes and Sec insertion systems in protozoan Apicomplexa parasites. We found that among these organisms, Plasmodium and Toxoplasma utilized Sec, whereas Cryptosporidium did not. However, Plasmodium had no homologs of known selenoproteins. By searching computationally for evolutionarily conserved selenocysteine insertion sequence (SECIS) elements, which are RNA structures involved in Sec insertion, we identified four unique Plasmodium falciparum selenoprotein genes. These selenoproteins were incorrectly annotated in PlasmoDB, were conserved in other Plasmodia and had no detectable homologs in other species. We provide evidence that two Plasmodium SECIS elements supported Sec insertion into parasite and endogenous selenoproteins when they were expressed in mammalian cells, demonstrating that the Plasmodium SECIS elements are functional and indicating conservation of Sec insertion between Apicomplexa and animals. Dependence of the plasmodial parasites on selenium suggests possible strategies for antimalarial drug development. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Nebraska, Dept Comp Sci, Lincoln, NE 68588 USA. Univ Giessen, Interdisziplinares Forschungszentrum, D-35392 Giessen, Germany. Univ Heidelberg, Zentrum Biochem, D-69120 Heidelberg, Germany. NCI, Mol Biol Selenium Sect, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013; OI Novoselov, Sergey/0000-0003-0104-6492 FU NIGMS NIH HHS [GM061603, R01 GM061603] NR 35 TC 43 Z9 44 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 2006 VL 34 IS 2 BP 496 EP 505 DI 10.1093/nar/gkj450 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 011TO UT WOS:000235291300020 PM 16428245 ER PT J AU Cruceanu, M Urbaneja, MA Hixson, CV Johnson, DG Datta, SA Fivash, MJ Stephen, AG Fisher, RJ Gorelick, RJ Casas-Finet, JR Rein, A Rouzina, I Williams, MC AF Cruceanu, M Urbaneja, MA Hixson, CV Johnson, DG Datta, SA Fivash, MJ Stephen, AG Fisher, RJ Gorelick, RJ Casas-Finet, JR Rein, A Rouzina, I Williams, MC TI Nucleic acid binding and chaperone properties of HIV-1 Gag and nucleocapsid proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; TIME-RESOLVED FLUORESCENCE; ZINC-FINGER STRUCTURES; PLUS-STRAND TRANSFER; STRONG STOP TRANSFER; T4 GENE-32 PROTEIN; ASSEMBLY IN-VITRO; REVERSE TRANSCRIPTION; GENOMIC RNA AB The Gag polyprotein of HIV-1 is essential for retroviral replication and packaging. The nucleocapsid (NC) protein is the primary region for the interaction of Gag with nucleic acids. In this study, we examine the interactions of Gag and its NC cleavage products (NCp15, NCp9 and NCp7) with nucleic acids using solution and single molecule experiments. The NC cleavage products bound DNA with comparable affinity and strongly destabilized the DNA duplex. In contrast, the binding constant of Gag to DNA was found to be similar to 10-fold higher than that of the NC proteins, and its destabilizing effect on dsDNA was negligible. These findings are consistent with the primary function of Gag as a nucleic acid binding and packaging protein and the primary function of the NC proteins as nucleic acid chaperones. Also, our results suggest that NCp7's capability for fast sequence-nonspecific nucleic acid duplex destabilization, as well as its ability to facilitate nucleic acid strand annealing by inducing electrostatic attraction between strands, likely optimize the fully processed NC protein to facilitate complex nucleic acid secondary structure rearrangements. In contrast, Gag's stronger DNA binding and aggregation capabilities likely make it an effective chaperone for processes that do not require significant duplex destabilization. C1 Northeastern Univ, Dept Phys, Dana Res Ctr 111, Boston, MA 02115 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Data Management Serv Inc, Frederick, MD 21702 USA. NCI, Prot Chem Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. Medimmune Inc, Gaithersburg, MD 20878 USA. Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. Northeastern Univ, Ctr Interdisciplinary Res Complex Syst, Dana Res Ctr 111, Boston, MA 02115 USA. RP Williams, MC (reprint author), Northeastern Univ, Dept Phys, Dana Res Ctr 111, 110 Forsyth St, Boston, MA 02115 USA. EM rouzina@cbs.umn.edu; mark@neu.edu RI Fisher, Robert/B-1431-2009; OI Datta, Siddhartha/0000-0002-4098-7490; Williams, Mark C./0000-0003-3219-376X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [GM-072462, R01 GM072462] NR 90 TC 89 Z9 91 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2006 VL 34 IS 2 BP 593 EP 605 DI 10.1093/nar/gkj458 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 011TO UT WOS:000235291300029 PM 16449201 ER PT J AU Harrigan, JA Wilson, DM Prasad, R Opresko, PL Beck, G May, A Wilson, SH Bohr, VA AF Harrigan, JA Wilson, DM Prasad, R Opresko, PL Beck, G May, A Wilson, SH Bohr, VA TI The Werner syndrome protein operates in base excision repair and cooperates with DNA polymerase beta SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; POLY(ADP-RIBOSE) POLYMERASE-1; HELICASE ACTIVITY; STRAND BREAKS; CELLS; DAMAGE; WRN; EXONUCLEASE; RECOMBINATION; CYTOTOXICITY AB Genome instability is a characteristic of cancer and aging, and is a hallmark of the premature aging disorder Werner syndrome (WS). Evidence suggests that the Werner syndrome protein (WRN) contributes to the maintenance of genome integrity through its involvement in DNA repair. In particular, biochemical evidence indicates a role for WRN in base excision repair (BER). We have previously reported that WRN helicase activity stimulates DNA polymerase beta (pol beta) strand displacement synthesis in vitro. In this report we demonstrate that WRN exonuclease activity can act cooperatively with pol beta, a polymerase lacking 3'-5' proofreading activity. Furthermore, using small interference RNA technology, we demonstrate that WRN knockdown cells are hypersensitive to the alkylating agent methyl methanesulfonate, which creates DNA damage that is primarily repaired by the BER pathway. In addition, repair assays using whole cell extracts from WRN knockdown cells indicate a defect in long patch (LP) BER. These findings demonstrate that WRN plays a direct role in the repair of methylation-induced DNA damage, and suggest a role for both WRN helicase and exonuclease activities together with pol beta during LP BER. C1 NIA, Lab Mol Gerontol, NIH, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Bethesda, MD 20892 USA. EM vbohr@nih.gov OI Opresko, Patricia/0000-0002-6470-2189 FU Intramural NIH HHS; NIA NIH HHS [AG03141]; NIGMS NIH HHS [GM01604] NR 45 TC 88 Z9 92 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 2006 VL 34 IS 2 BP 745 EP 754 DI 10.1093/nar/gkj475 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 011TO UT WOS:000235291300043 PM 16449207 ER PT J AU McDonald, JP Hall, A Gasparutto, D Cadet, J Ballantyne, J Woodgate, R AF McDonald, JP Hall, A Gasparutto, D Cadet, J Ballantyne, J Woodgate, R TI Novel thermostable Y-family polymerases: applications for the PCR amplification of damaged or ancient DNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SYN THYMINE DIMER; SULFOLOBUS-SOLFATARICUS; CRYSTAL-STRUCTURE; ERROR-PRONE; BYPASS; LESION; REPLICATION; SEQUENCE; ETA; SPECIFICITY AB For many years, Taq polymerase has served as the stalwart enzyme in the PCR amplification of DNA. However, a major limitation of Taq is its inability to amplify damaged DNA, thereby restricting its usefulness in forensic applications. In contrast, Y-family DNA polymerases, such as Dpo4 from Sulfolobus solfataricus, can traverse a wide variety of DNA lesions. Here, we report the identification and characterization of five novel thermostable Dpo4-like enzymes from Acidianus infernus, Sulfolobus shibatae, Sulfolobus tengchongensis, Stygiolobus azoricus and Sulfurisphaera ohwakuensis, as well as two recombinant chimeras that have enhanced enzymatic properties compared with the naturally occurring polymerases. The Dpo4-like polymerases are moderately processive, can substitute for Taq in PCR and can bypass DNA lesions that normally block Taq. Such properties make the Dpo4-like enzymes ideally suited for the PCR amplification of damaged DNA samples. Indeed, by using a blend of Taq and Dpo4-like enzymes, we obtained a PCR amplicon from ultraviolet-irradiated DNA that was largely unamplifyable with Taq alone. The inclusion of thermostable Dpo4-like polymerases in PCRs, therefore, augments the recovery and analysis of lesion-containing DNA samples, such as those commonly found in forensic or ancient DNA molecular applications. C1 NICHHD, Lab Genome Integrit, NIH, Bethesda, MD 20892 USA. Univ Cent Florida, Grad Program Biomol Sci, Orlando, FL 32816 USA. Univ Cent Florida, Dept Chem, Orlando, FL 32816 USA. Natl Ctr Forens Sci, Orlando, FL 32816 USA. CEA Grenoble, DRFMC, LCIB UMRE 3, CEA UJF,Lab Les Acides Nucl, F-38054 Grenoble 9, France. RP Woodgate, R (reprint author), NICHD, NIH, Bldg 6,Room 1A13,9000 Rockville, Bethesda, MD 20892 USA. EM woodgate@nih.gov FU Intramural NIH HHS NR 28 TC 25 Z9 26 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 2006 VL 34 IS 4 BP 1102 EP 1111 DI 10.1093/nar/gkj512 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 020PZ UT WOS:000235923500011 PM 16488882 ER PT J AU Chen, ZH Schneider, TD AF Chen, ZH Schneider, TD TI Comparative analysis of tandem T7-like promoter containing regions in enterobacterial genomes reveals a novel group of genetic islands SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BACTERIOPHAGE-T7 RNA-POLYMERASE; ESCHERICHIA-COLI; SALMONELLA-ENTERICA; VIBRIO-CHOLERAE; PSI-BLAST; PATHOGENICITY ISLANDS; INFORMATION-THEORY; INTEGRATION SITES; DNA-SEQUENCE; EVOLUTION AB Based on molecular information theory, 10 T7-like promoter models were built for the T7 group of phages and used to scan their host genomes and closely related genomes. 38 genomes were scanned and 12 clusters of tandem promoters were identified in nine enteropathogens. Comparative analysis of these tandem promoter-bearing regions reveals that they are similar to each other, forming prophage-like islands of 4-13 kb. Each island appears to contain two or three tandem T7-like promoters within a stretch of 150-620 bases, but there are no corresponding RNA polymerase (RNAP) genes. The promoters would transcribe two to five putative phage-related proteins, but none of these resemble known phage structural proteins. An integrase belonging to the Int family of site-specific recombinases is encoded upstream of the tandem promoters. A direct repeat of 17-24 bases was found on the ends of all 12 islands. Comparative analysis of the islands shows that these islands appear to have recombined with each other. These results suggest that the islands could encode a group of satellite phages. Activation and function of the islands may depend on transcription by a T7-like RNAP after infection by a T7-like phage or foreign DNA that encodes a T7-like RNAP. 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 66 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 2006 VL 34 IS 4 BP 1133 EP 1147 DI 10.1093/nar/gkj511 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 020PZ UT WOS:000235923500014 PM 16493139 ER PT J AU Deng, CX AF Deng, CX TI BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution SO NUCLEIC ACIDS RESEARCH LA English DT Review ID ANAPHASE-PROMOTING COMPLEX; FAMILIAL BREAST-CANCER; TUMOR-SUPPRESSOR; MITOTIC CHECKPOINT; AURORA-A; SUBCELLULAR-LOCALIZATION; CENTROSOME AMPLIFICATION; SPINDLE CHECKPOINT; OVARIAN-CANCER; MICE LACKING AB Germline mutations of the breast cancer associated gene 1 (BRCA1) predispose women to breast and ovarian cancers. BRCA1 is a large protein with multiple functional domains and interacts with numerous proteins that are involved in many important biological processes/pathways. Mounting evidence indicates that BRCA1 is involved in all phases of the cell cycle and regulates orderly events during cell cycle progression. BRCA1 deficiency, consequently causes abnormalities in the S-phase checkpoint, the G(2)/M checkpoint, the spindle checkpoint and centrosome duplication. The genetic instability caused by BRCA1 deficiency, however, also triggers cellular responses to DNA damage that blocks cell proliferation and induces apoptosis. Thus BRCA1 mutant cells cannot develop further into full-grown tumors unless this cellular defense is broken. Functional analysis of BRCA1 in cell cycle checkpoints, genome integrity, DNA damage response (DDR) and tumor evolution should benefit our understanding of the mechanisms underlying BRCA1 associated tumorigenesis, as well as the development of therapeutic approaches for this lethal disease. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 116 TC 243 Z9 263 U1 1 U2 21 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 2006 VL 34 IS 5 BP 1416 EP 1426 DI 10.1093/nar/gkl010 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027RL UT WOS:000236432900021 PM 16522651 ER PT J AU Fan, JS Zhan, M Shen, JK Martindale, JL Yang, XL Kawai, T Gorospe, M AF Fan, JS Zhan, M Shen, JK Martindale, JL Yang, XL Kawai, T Gorospe, M TI En masse nascent transcription analysis to elucidate regulatory transcription factors SO NUCLEIC ACIDS RESEARCH LA English DT Article ID B VIRUS ENHANCER; MESSENGER-RNA; C-MYB; GENE-EXPRESSION; TARGET GENES; RFX PROTEINS; DNA-BINDING; START SITE; CAMPTOTHECIN; PROMOTER AB Despite exhaustively informing about steady-state mRNA abundance, DNA microarrays have been used with limited success to identify regulatory transcription factors (TFs). The main limitation of this approach is that altered mRNA stability also strongly governs the patterns of expressed genes. Here, we used nuclear run-on assays and microarrays to systematically interrogate changes in nascent transcription in cells treated with the topoisomerase inhibitor camptothecin (CPT). Analysis of the promoters of coordinately transcribed genes after CPT treatment suggested the involvement of TFs c-Myb and Rfx1. The predicted CPT-dependent associations were subsequently confirmed by chromatin immunoprecipitation assays. Importantly, after RNAi-mediated knockdown of each TF, the CPT-elicited induction of c-Myb- and/or Rfx1-regulated mRNAs was diminished and the overall cellular response was impaired. The strategies described here permit the successful identification of the TFs responsible for implementing adaptive gene expression programs in response to cellular stimulation. C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. EM zhanmi@mail.nih.gov; myriam-gorospe@nih.gov FU Intramural NIH HHS NR 36 TC 10 Z9 11 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 2006 VL 34 IS 5 BP 1492 EP 1500 DI 10.1093/nar/gkj510 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027RL UT WOS:000236432900028 PM 16540593 ER PT J AU Hill, JW Evans, MK AF Hill, JW Evans, MK TI Dimerization and opposite base-dependent catalytic impairment of polymorphic S326COGG1 glycosylase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HOGG1 SER326CYS POLYMORPHISM; OXIDATIVELY DAMAGED DNA; LUNG-CANCER SUSCEPTIBILITY; AP LYASE ACTIVITY; REPAIR ENZYME; GENETIC POLYMORPHISMS; PROSTATE-CANCER; EXCISION-REPAIR; OGG1 PROTEIN; IN-VIVO AB Human 8-oxoguanine-DNA glycosylase (OGG1) is the major enzyme for repairing 8-oxoguanine (8-oxoG), a mutagenic guanine base lesion produced by reactive oxygen species (ROS). A frequently occurring OGG1 polymorphism in human populations results in the substitution of serine 326 for cysteine (S326C). The 326 C/C genotype is linked to numerous cancers, although the mechanism of carcinogenesis associated with the variant is unclear. We performed detailed enzymatic studies of polymorphic OGG1 and found functional defects in the enzyme. S326C OGG1 excised 8-oxoG from duplex DNA and cleaved abasic sites at rates 2- to 6-fold lower than the wild-type enzyme, depending upon the base opposite the lesion. Binding experiments showed that the polymorphic OGG1 binds DNA damage with significantly less affinity than the wild-type enzyme. Remarkably, gel shift, chemical cross-linking and gel filtration experiments showed that S326C both exists in solution and binds damaged DNA as a dimer. S326C OGG1 enzyme expressed in human cells was also found to have reduced activity and a dimeric conformation. The glycosylase activity of S326C OGG1 was not significantly stimulated by the presence of AP-endonuclease. The altered substrate specificity, lack of stimulation by AP-endonuclease 1 (APE1) and anomalous DNA binding conformation of S326C OGG1 may contribute to its linkage to cancer incidence. C1 NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Evans, MK (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. EM evansmi@grc.nia.nih.gov FU Intramural NIH HHS NR 72 TC 83 Z9 87 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 2006 VL 34 IS 5 BP 1620 EP 1632 DI 10.1093/nar/gkl060 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027RL UT WOS:000236432900041 PM 16549874 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, NA AF Shabalina, SA Ogurtsov, AY Spiridonov, NA TI A periodic pattern of mRNA secondary structure created by the genetic code SO NUCLEIC ACIDS RESEARCH LA English DT Article ID FOLDING FREE-ENERGIES; SYNONYMOUS MUTATIONS; SELECTION INTENSITY; SEQUENCE EVOLUTION; TRANSLATION RATE; CODING REGIONS; SILENT SITES; USAGE; EXPRESSION; GENOME AB Single-stranded mRNA molecules form secondary structures through complementary self-interactions. Several hypotheses have been proposed on the relationship between the nucleotide sequence, encoded amino acid sequence and mRNA secondary structure. We performed the first transcriptome-wide in silico analysis of the human and mouse mRNA foldings and found a pronounced periodic pattern of nucleotide involvement in mRNA secondary structure. We show that this pattern is created by the structure of the genetic code, and the dinucleotide relative abundances are important for the maintenance of mRNA secondary structure. Although synonymous codon usage contributes to this pattern, it is intrinsic to the structure of the genetic code and manifests itself even in the absence of synonymous codon usage bias at the 4-fold degenerate sites. While all codon sites are important for the maintenance of mRNA secondary structure, degeneracy of the code allows regulation of stability and periodicity of mRNA secondary structure. We demonstrate that the third degenerate codon sites contribute most strongly to mRNA stability. These results convincingly support the hypothesis that redundancies in the genetic code allow transcripts to satisfy requirements for both protein structure and RNA structure. Our data show that selection may be operating on synonymous codons to maintain a more stable and ordered mRNA secondary structure, which is likely to be important for transcript stability and translation. We also demonstrate that functional domains of the mRNA [5'-untranslated region (5'-UTR), CDS and 3'-UTR] preferentially fold onto themselves, while the start codon and stop codon regions are characterized by relaxed secondary structures, which may facilitate initiation and termination of translation. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. USDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Shabalina, SA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM shabalin@ncbi.nlm.nih.gov RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; FU Intramural NIH HHS NR 55 TC 102 Z9 104 U1 1 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. PY 2006 VL 34 IS 8 BP 2428 EP 2437 DI 10.1093/nar/gkl287 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 044UD UT WOS:000237697000036 PM 16682450 ER PT J AU Chakrabarti, S Lanczycki, CJ Panchenko, AR Przytycka, TM Thiessen, PA Bryant, SH AF Chakrabarti, S Lanczycki, CJ Panchenko, AR Przytycka, TM Thiessen, PA Bryant, SH TI Refining multiple sequence alignments with conserved core regions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN SEQUENCES; DATABASE; ALGORITHM; STRATEGY; TREES AB Accurate multiple sequence alignments of proteins are very important to several areas of computational biology and provide an understanding of phylogenetic history of domain families, their identification and classification. This article presents a new algorithm, REFINER, that refines a multiple sequence alignment by iterative realignment of its individual sequences with the predetermined conserved core (block) model of a protein family. Realignment of each sequence can correct misalignments between a given sequence and the rest of the profile and at the same time preserves the family's overall block model. Large-scale benchmarking studies showed a noticeable improvement of alignment after refinement. This can be inferred from the increased alignment score and enhanced sensitivity for database searching using the sequence profiles derived from refined alignments compared with the original alignments. A standalone version of the program is available by ftp distribution (ftp://ftp.ncbi.nih.gov/pub/REFINER) and will be incorporated into the next release of the Cn3D structure/alignment viewer. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 26 TC 27 Z9 27 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 2006 VL 34 IS 9 BP 2598 EP 2606 DI 10.1093/nar/gkl274 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 059WU UT WOS:000238763700020 PM 16707662 ER PT J AU Bacolla, A Collins, JR Gold, B Chuzhanova, N Yi, M Stephens, RM Stefanov, S Olsh, A Jakupciak, JP Dean, M Lempicki, RA Cooper, DN Wells, RD AF Bacolla, A Collins, JR Gold, B Chuzhanova, N Yi, M Stephens, RM Stefanov, S Olsh, A Jakupciak, JP Dean, M Lempicki, RA Cooper, DN Wells, RD TI Long homopurine center dot homopyrimidine sequences are characteristic of genes expressed in brain and the pseudoautosomal region SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRIPLEX-FORMING OLIGONUCLEOTIDES; NUCLEOTIDE EXCISION-REPAIR; MAJOR BREAKPOINT REGION; HUMAN INHERITED DISEASE; B DNA CONFORMATIONS; HUMAN GENOME; MAMMALIAN-CELLS; HELIX FORMATION; H-DNA; PERICENTRIC-INVERSION AB Homo(purine center dot pyrimidine) sequences (R center dot Y tracts) with mirror repeat symmetries form stable triplexes that block replication and transcription and promote genetic rearrangements. A systematic search was conducted to map the location of the longest R center dot Y tracts in the human genome in order to assess their potential function(s). The 814 R center dot Y tracts with >= 250 uninterrupted base pairs were preferentially clustered in the pseudoautosomal region of the sex chromosomes and located in the introns of 228 annotated genes whose protein products were associated with functions at the cell membrane. These genes were highly expressed in the brain and particularly in genes associated with susceptibility to mental disorders, such as schizophrenia. The set of 1957 genes harboring the 2886 R center dot Y tracts with >= 100 uninterrupted base pairs was additionally enriched in proteins associated with phosphorylation, signal transduction, development and morphogenesis. Comparisons of the >= 250 bp R center dot Y tracts in the mouse and chimpanzee genomes indicated that these sequences have mutated faster than the surrounding regions and are longer in humans than in chimpanzees. These results support a role for long R center dot Y tracts in promoting recombination and genome diversity during evolution through destabilization of chromosomal DNA, thereby inducing repair and mutation. C1 Texas A&M Univ, Ctr Genome Res, Inst Biosci & Technol, Syst Hlth Sci Ctr,Texas Med Ctr, Houston, TX 77030 USA. NCI Frederick, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. NCI Frederick, Lab Genom Divers, Ft Detrick, MD 21702 USA. Cardiff Univ, Biostat & Bioinformat Unit, Cardiff CF14 4XN, Wales. Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, Wales. Natl Inst Stand & Technol, DNA Technol Grp, Div Biotechnol, Gaithersburg, MD 20899 USA. SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. RP Wells, RD (reprint author), Texas A&M Univ, Ctr Genome Res, Inst Biosci & Technol, Syst Hlth Sci Ctr,Texas Med Ctr, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM rwells@ibt.tamhsc.edu RI Cooper, David/H-4384-2011; Lempicki, Richard/E-1844-2012; Bacolla, Albino/N-3877-2013; OI Cooper, David/0000-0002-8943-8484; Lempicki, Richard/0000-0002-7059-409X; Bacolla, Albino/0000-0003-0206-8423; Chuzhanova, Nadia/0000-0002-4655-3618; Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIEHS NIH HHS [ES11347, R01 ES011347]; NINDS NIH HHS [NS37554] NR 78 TC 38 Z9 39 U1 3 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 2006 VL 34 IS 9 BP 2663 EP 2675 DI 10.1093/nar/gkl354 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 059WU UT WOS:000238763700025 PM 16714445 ER PT J AU Cheng, WH Kusumoto, R Opresko, PL Sui, X Huang, SR Nicolette, ML Paull, TT Campisi, J Seidman, M Bohr, VA AF Cheng, WH Kusumoto, R Opresko, PL Sui, X Huang, SR Nicolette, ML Paull, TT Campisi, J Seidman, M Bohr, VA TI Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STALLED REPLICATION FORKS; DOUBLE-STRAND BREAKS; FANCONI-ANEMIA; SYNDROME CELLS; SYNDROME FIBROBLASTS; IONIZING-RADIATION; HELICASE BRIP1; IN-VIVO; REPAIR; DAMAGE AB Cells deficient in the Werner syndrome protein (WRN) or BRCA1 are hypersensitive to DNA interstrand cross-links (ICLs), whose repair requires nucleotide excision repair (NER) and homologous recombination (HR). However, the roles of WRN and BRCA1 in the repair of DNA ICLs are not understood and the molecular mechanisms of ICL repair at the processing stage have not yet been established. This study demonstrates that WRN helicase activity, but not exonuclease activity, is required to process DNA ICLs in cells and that WRN cooperates with BRCA1 in the cellular response to DNA ICLs. BRCA1 interacts directly with WRN and stimulates WRN helicase and exonuclease activities in vitro. The interaction between WRN and BRCA1 increases in cells treated with DNA cross-linking agents. WRN binding to BRCA1 was mapped to BRCA1 452-1079 amino acids. The BRCA1/BARD1 complex also associates with WRN in vivo and stimulates WRN helicase activity on forked and Holliday junction substrates. These findings suggest that WRN and BRCA1 act in a coordinated manner to facilitate repair of DNA ICLs. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Opresko, Patricia/0000-0002-6470-2189 FU Intramural NIH HHS NR 54 TC 55 Z9 58 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 2006 VL 34 IS 9 BP 2751 EP 2760 DI 10.1093/nar/gkl362 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 059WU UT WOS:000238763700032 PM 16714450 ER PT J AU Tjaden, B Goodwin, SS Opdyke, JA Guillier, M Fu, DX Gottesman, S Storz, G AF Tjaden, Brian Goodwin, Sarah S. Opdyke, Jason A. Guillier, Maude Fu, Daniel X. Gottesman, Susan Storz, Gisela TI Target prediction for small, noncoding RNAs in bacteria SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; MICRORNA TARGETS; SECONDARY STRUCTURE; DSRA RNA; REGULATORY RNA; WEB SERVER; OXYS RNA; IDENTIFICATION; EXPRESSION; PROTEIN AB Many small, noncoding RNAs in bacteria act as post-transcriptional regulators by basepairing with target mRNAs. While the number of characterized small RNAs (sRNAs) has steadily increased, only a limited number of the corresponding mRNA targets have been identified. Here we present a program, TargetRNA, that predicts the targets of these bacterial RNA regulators. The program was evaluated by assessing whether previously known targets could be identified. The program was then used to predict targets for the Escherichia coli RNAs RyhB, OmrA, OmrB and OxyS, and the predictions were compared with changes in whole genome expression patterns observed upon expression of the sRNAs. Our results show that TargetRNA is a useful tool for finding mRNA targets of sRNAs, although its rate of success varies between sRNAs. C1 Wellesley Coll, Dept Comp Sci, Wellesley, MA 02481 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20890 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Tjaden, B (reprint author), Wellesley Coll, Dept Comp Sci, Wellesley, MA 02481 USA. EM btjaden@wellesley.edu OI Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS NR 47 TC 140 Z9 149 U1 4 U2 12 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 2006 VL 34 IS 9 BP 2791 EP 2802 DI 10.1093/nar/gkl356 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 059WU UT WOS:000238763700036 PM 16717284 ER PT J AU Valente, AXCN Cusick, ME AF Valente, Andre X. C. N. Cusick, Michael E. TI Yeast protein interactome topology provides framework for coordinated-functionality SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; INTERACTION NETWORKS; COMPLEX NETWORKS; BUILDING-BLOCKS; CENTRALITY; PREDICTION; ORGANIZATION; BETWEENNESS; CELL AB The architecture of the network of protein-protein physical interactions in Saccharomyces cerevisiae is exposed through the combination of two complementary theoretical network measures, betweenness centrality and 'Q-modularity'. The yeast interactome is characterized by well-defined topological modules connected via a small number of inter-module protein interactions. Should such topological inter-module connections turn out to constitute a form of functional coordination between the modules, we speculate that this coordination is occurring typically in a pairwise fashion, rather than by way of high-degree hub proteins responsible for coordinating multiple modules. The unique non-hub-centric hierarchical organization of the interactome is not reproduced by gene duplication-and-divergence stochastic growth models that disregard global selective pressures. C1 NCI, Biometry Res Grp, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Valente, AXCN (reprint author), NCI, Biometry Res Grp, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM andre@deas.harvard.edu OI X. C. N. Valente, Andre/0000-0001-6684-0596 NR 61 TC 29 Z9 30 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 2006 VL 34 IS 9 BP 2812 EP 2819 DI 10.1093/nar/gkl325 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 059WU UT WOS:000238763700038 PM 16717286 ER PT J AU Mandal, D Dash, C Le Grice, SFJ Prasad, VR AF Mandal, Dibyakant Dash, Chandravanu Le Grice, Stuart F. J. Prasad, Vinayaka R. TI Analysis of HIV-1 replication block due to substitutions at F61 residue of reverse transcriptase reveals additional defects involving the RNase H function SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRAND DISPLACEMENT SYNTHESIS; MURINE LEUKEMIA-VIRUS; POLYPURINE TRACT; DNA-SYNTHESIS; NUCLEOCAPSID PROTEIN; POLYMERASE DOMAIN; CELL-LINE; IN-VIVO; TYPE-1 AB We reported previously that substitutions F61L, F61W, F61Y and F61A in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase affect strand displacement synthesis [T. S. Fisher, T. Darden and V. R. Prasad (2003) J. Mol. BioL, 325, 443-459]. We have now determined the effect of these mutations on HIV replication. All mutant viruses were replication defective. Measuring replication intermediates in infected cells did not reveal a specific block as all mutants displayed reduced DNA synthesis (wild-type > F61L > F61W > F61Y > F61A). Analysis of 2-LTR circle junctions revealed that F61W and F61Y mutants generated increased aberrant circle junctions. Circle junctions corresponding to F61Y included 3'-PPT insertions suggesting ribonuclease H defect. In vitro assays mimicking PPT primer generation indicated that F61L, F61W and F61Y mutant RTs were unaffected, while F61 A mutant cleaved both at PPT/U3 junction and at +6 with similar efficiencies. In assays measuring cleavage at the RNA/DNA junction to remove the PPT primer, all mutants were significantly affected with F61Y and F61A being most severely impaired. Our results show that (i) replication block of most mutants is due to more than one biochemical defect; (ii) mutations in polymerase domain can affect the function of a distal domain; and (iii) virological analyses of RT mutations can yield insight into structure-function relationship that is otherwise not obvious. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RP Prasad, VR (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM prasad@aecom.yu.edu FU Intramural NIH HHS; NIAID NIH HHS [R01 AI 30861, R01 AI030861, R21 AI030861, AI 30861, R37 AI030861]; NIDA NIH HHS [K99 DA024558, R00 DA024558] NR 38 TC 12 Z9 12 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 2006 VL 34 IS 10 BP 2853 EP 2863 DI 10.1093/nar/gkl.360 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069FD UT WOS:000239430900002 PM 16723431 ER PT J AU Wang, SB Zhang, JH Theel, S Barb, JJ Munson, PJ Danner, RL AF Wang, Shuibang Zhang, Jianhua Theel, Stephanie Barb, Jennifer J. Munson, Peter J. Danner, Robert L. TI Nitric oxide activation of Erk1/2 regulates the stability and translation of mRNA transcripts containing CU-rich elements SO NUCLEIC ACIDS RESEARCH LA English DT Article ID P38 MAP KINASE; PROTEIN ALPHA-CP; HNRNP-K; ERYTHROID-DIFFERENTIATION; 3'-UNTRANSLATED REGION; RESPONSE ELEMENT; BINDING-SITE; KAPPA-B; EXPRESSION; STABILIZATION AB Nitric oxide (NO center dot) can stabilize mRNA by activating p38 mitogen-activated protein kinase (MAPK). Here, transcript stabilization by NO center dot was investigated in human THP-1 cells using microarrays. After LPS pre-stimulation, cells were treated with actinomycin D and then exposed to NO center dot without or with the p38 MAPK inhibitor SB202190 (SB). The decay of 220 mRNAs was affected; most were stabilized by NO% Unexpectedly, SB often enhanced rather than antagonized transcript stability. NO center dot activated p38 MAPK and Erk1/2; SB blocked p38 MAPK, but further activated Erk1/2. RT-PCR confirmed that NO center dot and SB could additively stabilize certain mRNA transcripts, an effect abolished by Erk1/2 inhibition. In affected genes, these responses were associated with CU-rich elements (CURE) in 3'-untransiated regions (3'-UTR). NO center dot stabilized the mRNA of a CURE-containing reporter gene, while repressing translation. Dominant-negative Mek1, an Erk1/2 inhibitor, abolished this effect. NO center dot similarly stabilized, but blocked translation of MAP3K7IP2, a natural CURE-containing gene. NO center dot increased hnRNP translocation to the cytoplasm and binding to CURE. Over-expression of hnRNP K, like NO center dot, repressed translation of CURE-containing mRNA. These findings define a sequence-specific mechanism of NO center dot-triggered gene regulation that stabilizes mRNA, but represses translation. C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Danner, RL (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA. EM rdanner@cc.nih.gov FU Intramural NIH HHS NR 60 TC 16 Z9 17 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 2006 VL 34 IS 10 BP 3044 EP 3056 DI 10.1093/nar/gkl386 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069FD UT WOS:000239430900019 PM 16757573 ER PT J AU Shchyolkina, AK Kaluzhny, DN Arndt-Jovin, DJ Jovin, TM Zhurkin, VB AF Shchyolkina, Anna K. Kaluzhny, Dmitry N. Arndt-Jovin, Donna J. Jovin, Thomas M. Zhurkin, Victor B. TI Recombination R-triplex: H-bonds contribution to stability as revealed with minor base substitutions for adenine SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HOMOLOGOUS RECOMBINATION; MAJOR GROOVE; DNA-TRIPLEX; PARALLEL; HELIX; THERMODYNAMICS; FLUORESCENCE; DUPLEX; 2-AMINOPURINE; INTERMEDIATE AB Several cellular processes involve alignment of three nucleic acids strands, in which the third strand (DNA or RNA) is identical and in a parallel orientation to one of the DNA duplex strands. Earlier, using 2-aminopurine as a fluorescent reporter base, we demonstrated that a self-folding oligonucleotide forms a recombination-like structure consistent with the R-triplex. Here, we extended this approach, placing the reporter 2-aminopurine either in the 5'- or 3'-strand. We obtained direct evidence that the 3'-strand forms a stable duplex with the complementary central strand, while the 5'-strand participates in non-Watson-Crick interactions. Substituting 2,6-diaminopurine or 7-deazaadenine for adenine, we tested and confirmed the proposed hydrogen bonding scheme of the A*(T.A) R-type triplet. The adenine substitutions expected to provide additional H-bonds led to triplex structures with increased stability, whereas the substitutions consistent with a decrease in the number of H-bonds destabilized the triplex. The triplex formation enthalpies and free energies exhibited linear dependences on the number of H-bonds predicted from the A*(T.A) triplet scheme. The enthalpy of the 10 nt long intramolecular triplex of -100 kJ.mol(-1) demonstrates that the R-triplex is relatively unstable and thus an ideal candidate for a transient intermediate in homologous recombination, t-loop formation at the mammalian telomere ends, and short RNA invasion into a duplex. On the other hand, the impact of a single H-bond, 18 kJ.mol(-1), is high compared with the overall triplex formation enthalpy. The observed energy advantage of a 'correct' base in the third strand opposite the Watson-Crick base pair may be a powerful mechanism for securing selectivity of recognition between the single strand and the duplex. C1 Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia. Max Planck Inst Biophys Chem, Dept Mol Biol, D-37070 Gottingen, Germany. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. RP Zhurkin, VB (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow 119991, Russia. EM zhurkin@nih.gov RI Kaluzhny, Dmitry/G-7256-2014 NR 32 TC 15 Z9 15 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 2006 VL 34 IS 11 BP 3239 EP 3245 DI 10.1093/nar/gkl431 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 075TJ UT WOS:000239907800012 PM 16798913 ER PT J AU Picher, AJ Garcia-Diaz, M Bebenek, K Pedersen, LC Kunkel, TA Blanco, L AF Picher, Angel J. Garcia-Diaz, Miguel Bebenek, Katarzyna Pedersen, Lars C. Kunkel, Thomas A. Blanco, Luis TI Promiscuous mismatch extension by human DNA polymerase lambda SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STRAND BREAK REPAIR; ACTIVE-SITE; POL LAMBDA; MU; YEAST; MECHANISMS; FIDELITY; TRANSFERASE; ALIGNMENT; PROTEIN AB DNA polymerase lambda (Pol lambda) is one of several DNA polymerases suggested to participate in base excision repair (BER), in repair of broken DNA ends and in translesion synthesis. It has been proposed that the nature of the DNA intermediates partly determines which polymerase is used for a particular repair reaction. To test this hypothesis, here we examine the ability of human Pol lambda to extend mismatched primer-termini, either on 'open' template-primer substrates, or on its preferred substrate, a 1 nt gapped-DNA molecule having a 5'-phosphate. Interestingly, Pol lambda extended mismatches with an average efficiency of approximate to 10(-2) relative to matched base pairs. The match and mismatch extension catalytic efficiencies obtained on gapped molecules were approximate to 260-fold higher than on template-primer molecules. A crystal structure of Pol lambda in complex with a single-nucleotide gap containing a dG.dGMP mismatch at the primer-terminus (2.40 angstrom) suggests that, at least for certain mispairs, Pol lambda is unable to differentiate between matched and mismatched termini during the DNA binding step, thus accounting for the relatively high efficiency of mismatch extension. This property of Pol lambda suggests a potential role as a 'mismatch extender' during non-homologous end joining (NHEJ), and possibly during translesion synthesis. C1 Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Blanco, L (reprint author), Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. EM lblanco@cbm.uam.es RI Blanco, Luis/I-1848-2015 FU Intramural NIH HHS NR 50 TC 28 Z9 28 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 2006 VL 34 IS 11 BP 3259 EP 3266 DI 10.1093/nar/gkl377 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 075TJ UT WOS:000239907800014 PM 16807316 ER PT J AU Zhang, Y Liu, XS Liu, QR Wei, LP AF Zhang, Yong Liu, X. Shirley Liu, Qing-Rong Wei, Liping TI Genome-wide in silico identification and analysis of cis natural antisense transcripts (cis-NATs) in ten species SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS; DATABASE RESOURCES; OVERLAPPING GENES; NATIONAL-CENTER; DNA-SEQUENCE; RNA; EXPRESSION; SENSE; EUKARYOTES; ANNOTATION AB We developed a fast, integrative pipeline to identify cis natural antisense transcripts (cis-NATs) at genome scale. The pipeline mapped mRNAs and ESTs in UniGene to genome sequences in GoldenPath to find overlapping transcripts and combining information from coding sequence, poly(A) signal, poly(A) tail and splicing sites to deduce transcription orientation. We identified cis-NATs in 10 eukaryotic species, including 7830 candidate sense-antisense (SA) genes in 3915 SA pairs in human. The abundance of SA genes is remarkably low in worm and does not seem to be caused by the prevalence of operons. Hundreds of SA pairs are conserved across different species, even maintaining the same overlapping patterns. The convergent SA class is prevalent in fly, worm and sea squirt, but not in human or mouse as reported previously. The percentage of SA genes among imprinted genes in human and mouse is 24-47%, a range between the two previous reports. There is significant shortage of SA genes on Chromosome X in human and mouse but not in fly or worm, supporting X-inactivation in mammals as a possible cause. SA genes are over-represented in the catalytic activities and basic metabolism functions. All candidate cis-NATs can be downloaded from http://nats.cbi.pku.edu.cn/download/. C1 Peking Univ, Coll Life Sci, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NIDA, Mol Neurobiol Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Wei, LP (reprint author), Peking Univ, Coll Life Sci, Ctr Bioinformat, Natl Lab Prot Engn & Plant Genet Engn, Beijing 100871, Peoples R China. EM weilp@mail.cbi.pkku.edu.cn RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU NHGRI NIH HHS [R01 HG004069, R01 HG004069-01] NR 66 TC 109 Z9 110 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 2006 VL 34 IS 12 BP 3465 EP 3475 DI 10.1093/nar/gkl473 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 075TL UT WOS:000239908000013 PM 16849434 ER PT J AU Takeda, J Suzuki, Y Nakao, M Barrero, RA Koyanagi, KO Jin, LH Motono, C Hata, H Isogai, T Nagai, K Otsuki, T Kuryshev, V Shionyu, M Yura, K Go, M Thierry-Mieg, J Thierry-Mieg, D Wiemann, S Nomura, N Sugano, S Gojobori, T Imanishi, T AF Takeda, Jun-ichi Suzuki, Yutaka Nakao, Mitsuteru Barrero, Roberto A. Koyanagi, Kanako O. Jin, Lihua Motono, Chie Hata, Hiroko Isogai, Takao Nagai, Keiichi Otsuki, Tetsuji Kuryshev, Vladimir Shionyu, Masafumi Yura, Kei Go, Mitiko Thierry-Mieg, Jean Thierry-Mieg, Danielle Wiemann, Stefan Nomura, Nobuo Sugano, Sumio Gojobori, Takashi Imanishi, Tadashi TI Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PRE-MESSENGER-RNA; OPEN READING FRAMES; HUMAN GENOME; MAMMALIAN GENOMES; KAPPA-B; PROTEINS; MOUSE; PROMOTERS; COMPLEX; CELLS AB We report the first genome-wide identification and characterization of alternative splicing in human gene transcripts based on analysis of the full-length cDNAs. Applying both manual and computational analyses for 56 419 completely sequenced and precisely annotated full-length cDNAs selected for the H-Invitational human transcriptome annotation meetings, we identified 6877 alternative splicing genes with 18 297 different alternative splicing variants. A total of 37 670 exons were involved in these alternative splicing events. The encoded protein sequences were affected in 6005 of the 6877 genes. Notably, alternative splicing affected protein motifs in 3015 genes, subcellular localizations in 2982 genes and transmembrane domains in 1348 genes. We also identified interesting patterns of alternative splicing, in which two distinct genes seemed to be bridged, nested or having overlapping protein coding sequences (CDSs) of different reading frames (multiple CDS). In these cases, completely unrelated proteins are encoded by a single locus. Genome-wide annotations of alternative splicing, relying on full-length cDNAs, should lay firm groundwork for exploring in detail the diversification of protein function, which is mediated by the fast expanding universe of alternative splicing variants. C1 Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan. Japan Biol Informat Consortium, Integrated Database Grp, Japan Biol Informat Res Ctr, Koto Ku, Tokyo 1350064, Japan. Univ Tokyo, Dept Med Genome Sci, Grad Sch Frontier Sci, Chiba 2778562, Japan. Natl Inst Adv Sci & Technol, Computat Biol Res Ctr, Koto Ku, Tokyo 1350064, Japan. Kazusa DNA Res Inst, Chiba 2920818, Japan. Natl Inst Genet, Ctr Informat Biol & DDBJ, Shizuoka 4118540, Japan. Hokkaido Univ, Grad Sch Informat Sci & Technol, Sapporo, Hokkaido 0600814, Japan. Reverse Proteom Res Inst, Chiba 2920818, Japan. Helix Res Inst, Chiba 2920812, Japan. Hitachi Ltd, Cent Res Lab, Kokubunji, Tokyo 1858601, Japan. German Canc Res Ctr, Div Mol Genome Anal, D-69120 Heidelberg, Germany. Nagahama Inst Biosci & Technol, Fac Biosci, Shiga 5260829, Japan. Japan Atom Energy Agcy, Quantum Bioinformat Team, Ctr Computat Sci & Engn, Kyoto 6190215, Japan. Ochanomizu Univ, Bunkyo Ku, Tokyo 1128610, Japan. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Montpellier 2, Phys Math Lab, Ctr Natl Rech Sci, F-34095 Montpellier, France. RP Imanishi, T (reprint author), Natl Inst Adv Ind Sci & Technol, Biol Informat Res Ctr, Koto Ku, AIST Bio IT Res Bldg,Aomi 2-42, Tokyo 1350064, Japan. EM imanishi@jbirc.aist.go.jp RI Koyanagi, Kanako/D-6354-2012; Wiemann, Stefan/E-4424-2013; Jun-ichi, Takeda/I-7483-2014; THIERRY-MIEG, Jean/F-1975-2017 OI Koyanagi, Kanako/0000-0003-1615-5077; Wiemann, Stefan/0000-0003-4683-3174; Jun-ichi, Takeda/0000-0001-5367-5608; THIERRY-MIEG, Jean/0000-0002-0396-6789 NR 44 TC 32 Z9 36 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 2006 VL 34 IS 14 BP 3917 EP 3928 DI 10.1093/nar/gkl507 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 085DP UT WOS:000240583800013 PM 16914452 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Wheeler, DL AF Benson, Dennis A. Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Wheeler, David L. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; ANNOTATION AB GenBank (R) is a comprehensive database that contains publicly available DNA sequences for more than 205 000 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 Europe and the DNA Data Bank of Japan ensures 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 www.ncbi.nlm.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov NR 11 TC 305 Z9 322 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. PD JAN 1 PY 2006 VL 34 SI SI BP D16 EP D20 DI 10.1093/nar/gkj157 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700005 PM 16381837 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI The Molecular Biology Database Collection: 2006 update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN FAMILIES AB The NAR Molecular Biology Database Collection is a public online resource that contains links to all databases described in this issue of Nucleic Acids Research. In addition, this collection lists databases that have been featured in previous issues of NAR, as well as selected other databases that are freely available to the public and may be useful to the molecular biologist. The 2006 update includes 858 databases, 139 more than the previous one. The data-bases come with brief summaries, many of which have been updated recently. Each database is assigned a stable accession number that does not change if the database moves to a new location and its URL, authors' names or the contact person address are updated. The complete database list and summaries are available online at the Nucleic Acids Research website http://nar.oxfordjournals.org/. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Natl Inst Hlth, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 16 TC 46 Z9 50 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2006 VL 34 SI SI BP D3 EP D5 DI 10.1093/nar/gkj162 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700002 PM 16381871 ER PT J AU Kumar, MDS Bava, KA Gromiha, MM Prabakaran, P Kitajima, K Uedaira, H Sarai, A AF Kumar, M. D. Shaji Bava, K. Abdulla Gromiha, M. Michael Prabakaran, Ponraj Kitajima, Koji Uedaira, Hatsuho Sarai, Akinori TI ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MUTANTS AB ProTherm and ProNIT are two thermodynamic databases that contain experimentally determined thermodynamic parameters of protein stability and protein-nucleic acid interactions, respectively. The current versions of both the databases have considerably increased the total number of entries and enhanced search interface with added new fields, improved search, display and sorting options. As on September 2005, ProTherm release 5.0 contains 17 113 entries from 771 proteins, retrieved from 1497 scientific articles (similar to 20% increase in data from the previous version). ProNIT release 2.0 contains 4900 entries from 273 research articles, representing 158 proteins. Both databases can be queried using WWW interfaces. Both quick search and advanced search are provided on this web page to facilitate easy retrieval and display of the data from these databases. ProTherm is freely available online at http://gibk26.bse.kyutech.ac.jp/jouhou/Protherm/protherm. html and ProNIT at http://gibk26.bse. kyutech.ac.jp/jouhou/pronit/pronit.html. C1 Kyushu Inst Technol, Dept Biosci & Bioinformat, Iizuka, Fukuoka 8208502, Japan. Adv Technol Inst Inc, Shiki, Saitama 3530006, Japan. Natl Inst Adv Ind Sci & Technol, CBRC, Koto Ku, Tokyo 1350064, Japan. NCI, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. Tsukuba Mat Informat Lab, Tsukuba, Ibaraki 3050051, Japan. RP Sarai, A (reprint author), Kyushu Inst Technol, Dept Biosci & Bioinformat, 680-4 Kawazu, Iizuka, Fukuoka 8208502, Japan. EM sarai@bse.kyutech.ac.jp RI Ponraj, Prabakaran/D-6325-2011 NR 13 TC 159 Z9 163 U1 1 U2 16 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. PD JAN 1 PY 2006 VL 34 SI SI BP D204 EP D206 DI 10.1093/nar/gkj103 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700043 PM 16381846 ER PT J AU Lanz, RB Jericevic, Z Zuercher, WJ Watkins, C Steffen, DL Margolis, R McKenna, NJ AF Lanz, Rainer B. Jericevic, Zeljko Zuercher, William J. Watkins, Chris Steffen, David L. Margolis, Ronald McKenna, Neil J. TI Nuclear Receptor Signaling Atlas (www.nursa.org): hyperlinking the nuclear receptor signaling community SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SUPERFAMILY AB The nuclear receptor signaling (NRS) field has generated a substantial body of information on nuclear receptors, their ligands and coregulators, with the ultimate goal of constructing coherent models of the biological and clinical significance of these molecules. As a component of the Nuclear Receptor Signaling Atlas (NURSA)- the development of a functional atlas of nuclear receptor biology - the NURSA Bioinformatics Resource is developing a strategy to organize and integrate legacy and future information on these molecules in a single web-based resource (www.nursa.org). This entails parallel efforts of (i) developing an appropriate software framework for handling datasets from NURSA laboratories and (ii) designing strategies for the curation and presentation of public data relevant to NRS. To illustrate our approach, we have described here in detail the development of a web-based interface for the NURSA quantitative PCR nuclear receptor expression dataset, incorporating bioinformatics analysis which provides novel perspectives on functional relationships between these molecules. We anticipate that the free and open access of the community to a platform for data mining and hypothesis generation strategies will be a significant contribution to the progress of research in this field. C1 Baylor Coll Med, Dept Mol & Cellular Biol M602, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet M620, Houston, TX 77030 USA. GlaxoSmithKline Inc, Discovery Res Chem, Res Triangle Pk, NC 27709 USA. NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Lanz, RB (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol M602, 1 Baylor Plaza, Houston, TX 77030 USA. EM rlanz@bcm.tmc.edu; nmckenna@bcm.tmc.edu OI McKenna, Neil/0000-0001-6689-0104 FU NIDDK NIH HHS [U19 DK62434, U19 DK062434] NR 15 TC 14 Z9 14 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 2006 VL 34 SI SI BP D221 EP D226 DI 10.1093/nar/gkj029 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700047 PM 16381851 ER PT J AU Packer, BR Yeager, M Burdett, L Welch, R Beerman, M Qi, LQ Sicotte, H Staats, B Acharya, M Crenshaw, A Eckert, A Puri, V Gerhard, DS Chanock, SJ AF Packer, Bernice R. Yeager, Meredith Burdett, Laura Welch, Robert Beerman, Michael Qi, Liqun Sicotte, Hugues Staats, Brian Acharya, Mekhala Crenshaw, Andrew Eckert, Andrew Puri, Vinita Gerhard, Daniela S. Chanock, Stephen J. TI SNP500Cancer: a public resource for sequence validation, assay development, and frequency analysis for genetic variation in candidate genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-CODING LOCI; LINKAGE DISEQUILIBRIUM; POLYMORPHIC SITES; HUMAN GENOME; SELECTION; VISUALIZATION; INFORMATION; DIVERSITY; DATABASE; NCBI AB The SNP500Cancer database provides sequence and genotype assay information for candidate SNPs useful inmapping complex diseases, such as cancer. The database is an integral component of the NCl Cancer Genome Anatomy Project (http://cgap.nci.nih.gov). SNP500Cancer reports sequence analysis of anonymized control DNA samples (n = 102 Coriell samples representing four self-described ethnic groups: African/African-American, Caucasian, Hispanic and Pacific Rim). The website is searchable by gene, chromosome, gene ontology pathway, dbSNP ID and SNP500Cancer SNP ID. As of October 2005, the database contains > 13 400 SNPs, 9124 of which have been sequenced in the SNP500Cancer population. For each analysed SNP, gene location and > 200 bp of surrounding annotated sequence (including nearby SNPs) are provided, with frequency information in total and per subpopulation as well as calculation of Hardy-Weinberg equilibrium for each subpopulation. The website provides the conditions for validated sequencing and genotyping assays, as well as genotype results for the 102 samples, in both viewable and downloadable formats. A subset of sequence validated SNPs with minor allele frequency > 5% are entered into a high-throughput pipeline for genotyping analysis to determine concordance for the same 102 samples. In addition, the results of genotype analysis for select validated SNP assays (defined as 100% concordance between sequence analysis and genotype results) are posted for an additional 280 samples drawn from the Human Diversity Panel (HDP). SNP500Cancer provides an invaluable resource for investigators to select SNPs for analysis, design genotyping assays using validated sequence data, choose selected assays already validated on one or more genotyping platforms, and select reference standards for genotyping assays. The SNP500Cancer database is freely accessible via the web page at http://snp500cancer.nci.nih.gov. C1 NCI, Intramural Res Support Program, SAIC Frederick, FCRRDC, Frederick, MD 21701 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. George Mason Univ, Dept Bioinformat, Manassas, VA USA. NCI, Off Canc Genom, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Gaithersburg, MD USA. RP Packer, BR (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, FCRRDC, Frederick, MD 21701 USA. EM packerb@mail.nih.gov FU Intramural NIH HHS NR 21 TC 210 Z9 215 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2006 VL 34 SI SI BP D617 EP D621 DI 10.1093/nar/gkj151 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700131 PM 16381944 ER PT J AU Sullivan, JC Ryan, JF Watson, JA Webb, J Mullikin, JC Rokhsar, D Finnerty, JR AF Sullivan, James C. Ryan, Joseph F. Watson, James A. Webb, Jeramy Mullikin, James C. Rokhsar, Daniel Finnerty, John R. TI StellaBase: The Nematostella vectensis Genomics Database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SEA-ANEMONE; ASEXUAL REPRODUCTION; GENE-EXPRESSION; ANCESTRAL ROLE; EST ANALYSIS; EVOLUTION; ANTHOZOA; CNIDARIA; STEPHENSON; PREDICTION AB StellaBase, the Nematostella vectensis Genomics Database, is a web-based resource that will facilitate desktop and bench-top studies of the starlet sea anemone. Nematostella is an emerging model organism that has already proven useful for addressing fundamental questions in developmental evolution and evolutionary genomics. StellaBase allows users to query the assembled Nematostella genome, a confirmed gene library, and a predicted genome using both keyword and homology based search functions. Data provided by these searches will elucidate gene family evolution in early animals. Unique research tools, including a Nematostella genetic stock library, a primer library, a literature repository and a gene expression library will provide support to the burgeoning Nematostella research community. The development of StellaBase accompanies significant upgrades to CnidBase, the Cnidarian Evolutionary Genomics Database. With the completion of the first sequenced cnidarian genome, genome comparison tools have been added to CnidBase. In addition, StellaBase provides a framework for the integration of additional species-specific databases into CnidBase. StellaBase is available at http://www.stellabase.org. C1 Boston Univ, Dept Biol, Boston, MA 02215 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. NHGRI, Bethesda, MD 20892 USA. Joint Gen Inst Univ, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. RP Finnerty, JR (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. EM jrf3@bu.edu RI Finnerty, John/B-6564-2011 FU Intramural NIH HHS NR 33 TC 84 Z9 87 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. PD JAN 1 PY 2006 VL 34 SI SI BP D495 EP D499 DI 10.1093/nar/gkj020 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700108 PM 16381919 ER PT J AU Wheeler, DL Barrett, T Benson, DA Bryant, SH Canese, K Chetvernin, V Church, DM DiCuccio, M Edgar, R Federhen, S Geer, LY Helmberg, W Kapustin, Y Kenton, DL Khovayko, O Lipman, DJ Madden, TL Maglott, DR Ostell, J Pruitt, KD Schuler, GD Schriml, LM Sequeira, E Sherry, ST Sirotkin, K Souvorov, A Starchenko, G Suzek, TO Tatusov, R Tatusova, TA Wagner, L Yaschenko, E AF Wheeler, David L. Barrett, Tanya Benson, Dennis A. Bryant, Stephen H. Canese, Kathi Chetvernin, Vyacheslav Church, Deanna M. DiCuccio, Michael Edgar, Ron Federhen, Scott Geer, Lewis Y. Helmberg, Wolfgang Kapustin, Yuri Kenton, David L. Khovayko, Oleg Lipman, David J. Madden, Thomas L. Maglott, Donna R. Ostell, James Pruitt, Kim D. Schuler, Gregory D. Schriml, Lynn M. Sequeira, Edwin Sherry, Stephen T. Sirotkin, Karl Souvorov, Alexandre Starchenko, Grigory Suzek, Tugba O. Tatusov, Roman Tatusova, Tatiana A. Wagner, Lukas Yaschenko, Eugene TI Database resources of the national center for biotechnology information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENOME DATABASE; PSI-BLAST; PROTEIN; ENTREZ; NCBI; SEQUENCE; SEARCH; GENE; TOOL AB In addition to maintaining the GenBank( R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides analysis and retrieval resources for the data in GenBank and other biological data made available through NCBI's Web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Entrez Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Electronic PCR, OrfFinder, Spidey, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, Cancer Chromosomes, Entrez Genomes and related tools, the Map Viewer, Model Maker, Evidence Viewer, Clusters of Orthologous Groups, Retroviral Genotyping Tools, HIV-1, Human Protein Interaction Database, SAGEmap, Gene Expression Omnibus, Entrez Probe, GENSAT, Online Mendelian Inheritance in Man, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool and the PubChem suite of small molecule databases. 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.nlm.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 Geer, Lewis/H-2714-2014; Suzek, Tugba/B-6943-2015 NR 31 TC 289 Z9 310 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 2006 VL 34 SI SI BP D173 EP D180 DI 10.1093/nar/gkj158 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 067MR UT WOS:000239307700037 PM 16381840 ER PT J AU Hu, ZL Zhang, AX Storz, G Gottesman, S Leppla, SH AF Hu, ZL Zhang, AX Storz, G Gottesman, S Leppla, SH TI An antibody-based microarray assay for small RNA detection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; GENE-EXPRESSION; REGULATORY RNA; DNA MICROARRAY; HFQ; TRANSLATION; GENOMICS; TARGETS; PROTEIN AB Detection of RNAs on microarrays is rapidly becoming a standard approach for molecular biologists. However, current methods frequently discriminate against structured and/or small RNA species. Here we present an approach that bypasses these problems. Unmodified RNA is hybridized directly to DNA microarrays and detected with the high-affinity, nucleotide sequence-independent, DNA/RNA hybrid-specific mouse monoclonal antibody S9.6. Subsequent reactions with a fluorescently-labeled anti-mouse IgG antibody or biotin-labeled anti-mouse IgG together with fluorescently labeled streptavidin produces a signal that can be measured in a standard microarray scanner. The antibody-based method was able to detect low abundance small RNAs of Escherichia coli much more efficiently than the commonly-used cDNA-based method. A specific small RNA was detected in amounts of 0.25 mu mol (i.e. concentration of 10 mu M in a 25 mu l reaction). The method is an efficient, robust and inexpensive technique that allows quantitative analysis of gene expression and does not discriminate against short or structured RNAs. C1 NIAID, Bacterial Toxins & Therapeut Sect, NIH, NCI, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, NCI, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov OI Storz, Gisela/0000-0001-6698-1241 FU Intramural NIH HHS NR 18 TC 55 Z9 58 U1 3 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 2006 VL 34 IS 7 AR e52 DI 10.1093/nar/gkl142 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 042IZ UT WOS:000237522900001 PM 16614443 ER PT J AU Jacobson, KA Costanzi, S Kim, SK Roh, E Joshi, BV Tchilibon, S Duong, HT Gao, ZG AF Jacobson, Kenneth A. Costanzi, Stefano Kim, Soo-Kyung Roh, Eunjoo Joshi, Bhalchandra V. Tchilibon, Susanna Duong, Heng T. Gao, Zhan-Guo TI Action of nucleosides and nucleotides at 7 transmembrane-spanning receptors 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 purines; neoceptor; mutagenesis; pyrimidines; molecular modeling ID A(3) ADENOSINE RECEPTOR; P2Y(1) RECEPTOR; ANTAGONISTS; AGONISTS; DERIVATIVES; A(2A); SELECTIVITY; ACTIVATION; POTENT; CONFORMATION AB Ribose ring-constrained nucleosides and nucleotides to act at cell-surface purine recesptors have been designed and synthesized. At the P2Y(1) nucleotide receptor and the A(3) adenosine receptor (AR) the North envelope conformation of ribose is highly preferred. We have applied mutagenesis and rhodopsin-based homology modeling to the study of purine receptors and used the structural insights gained to assist in the design of novel ligands. Two subgroups of P2Y receptors have been defined, containing different sets of cationic residues for coordinating the phosphate groups. Modeling/mutagenesis of adenosine receptors has focused on determinants of intrinsic efficacy in adenosine derivatives and on a conserved Trp residue (6.48) which is involved in the activation process. The clinical use of adenosine agonists as cytoprotective agents has been limited by the widespread occurrence of ARs, thus, leading to undesirable side effects of exogenously administered adenosine derivatives. In order to overcome the inherent nonselectivity of activating the native receptors, we have introduced the concept of neoceptors. By this strategy, intended for eventual use in gene therapy, the putative ligand binding site of a G protein-coupled receptor is reengineered for activation by synthetic agonists (neoligands) built to have a structural complementarity. Using a rational design process we have identified neoceptor-neoligand pairs which are pharmacologically orthogonal with respect to the native species. C1 NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), 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; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 NR 33 TC 4 Z9 4 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 2006 VL 25 IS 12 BP 1425 EP 1436 DI 10.1080/15257770600919027 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108BJ UT WOS:000242214700009 PM 17067963 ER PT J AU Koralek, DO Bertone-Johnson, ER Leitzmann, MF Sturgeon, SR Lacey, JV Schairer, C Schatzkin, A AF Koralek, Daniel O. Bertone-Johnson, Elizabeth R. Leitzmann, Michael F. Sturgeon, Susan R. Lacey, James V., Jr. Schairer, Catherine Schatzkin, Arthur TI Relationship between calcium, lactose, vitamin D, and dairy products and ovarian cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID BREAST-CANCER; GALACTOSE CONSUMPTION; REPLACEMENT THERAPY; LACTASE PERSISTENCE; PROSPECTIVE COHORT; UNITED-STATES; RISK; DIET; METABOLISM; MICE AB Few prospective studies of the relationship between intake of dairy foods, calcium, vitamin D, and lactose and ovarian cancer have been conducted, and results have been largely inconsistent. Two recent studies found significant increased risk with frequent dairy consumption and perhaps with high intakes of calcium or lactose. The authors investigated the association between these foods and nutrients and ovarian cancer risk among 31,925 subjects in the Breast Cancer Detection Demonstration Project follow-up cohort. Multivariable (MV) relative risks (RRs) adjusted for age, parity, and other factors were estimated using Cox proportional hazards models. Over an average follow-up of 8.3 yr, 146 incident ovarian cancer cases were confirmed. Higher intakes of total dairy food (comparing four or more servings per day vs. less than one serving per day) were associated with a statistically significant decreased risk of ovarian cancer, although the trend was not significant (MV RR = 0.42; 95% confidence interval (CI) = 0.20 - 0.89; P for trend = 0.07). Comparing extreme quartiles, we observed a statistically nonsignificant inverse association between high dietary calcium intake and ovarian cancer (RR = 0.67; 95% CI = 0.43, 1.04; P for trend = 0.08). No statistically significant relations were found for consumption of specific dairy foods, lactose, or vitamin D and ovarian cancer risk. The possibility of a decreased risk of ovarian cancer for dietary calcium merits further evaluation. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Koralek, DO (reprint author), Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. EM dkoralek@unc.edu FU Intramural NIH HHS NR 33 TC 19 Z9 20 U1 1 U2 10 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 2006 VL 56 IS 1 BP 22 EP 30 DI 10.1207/s15327914nc5601_4 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 126BN UT WOS:000243487300004 PM 17176214 ER PT J AU Milner, JA AF Milner, John A. TI Diet and cancer: Facts and controversies SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article; Proceedings Paper CT International Workshop on Diet and Cancer Prevention CY NOV 11-12, 2005 CL Palermo, ITALY SP Amer Hlth Fdn, NCI ID BIOACTIVE FOOD COMPONENTS; SELENIUM SUPPLEMENTATION; MOLECULAR TARGETS; LUNG-CANCER; NUTRITIONAL PREVENTION; MASS-SPECTROMETRY; PROSTATE-CANCER; GENE-EXPRESSION; TRANSGENIC MICE; BETA-CAROTENE AB Evidence continues to mount that dietary components are important determinants of cancer risk and tumor behavior Although these linkages are fascinating, numerous inconsistencies are also evident in the literature. Although multifactorial, these discrepancies likely reflect variation in the ability of food constituents to reach and/or modify critical molecular targets. Genetic polymorphisms can alter the response to dietary components (nutrigenetic effect) by influencing the absorption, metabolism, or site of action. Likewise, variation in DNA methylation patterns and other epigenomic events that influence overall gene expression can influence the biological response to food components and vice versa. Fluctuations in the ability of food components to increase or depress gene expression (nutritional transcriptomic effect) may also account for some of the inconsistencies in the response to foods. Functional proteomic studies that capture all of the proteins produced by a species and link them to physiological significance within the cell will be fundamental to understanding the relationship between dietary interventions, proteome changes, and cancer Although a bioactive food component may influence a number of key molecular events that are involved with cancer prevention, to do so it must achieve an effective concentration within the target site, be in the correct metabolic form, and bring about a change in one or more small molecular weight signals in the cellular milleau (metabolomic effects). Fundamental to assessing and evaluating the significance of the interrelationships among bioactive food components with nutrigenetics, nutritional epigenomics, nutritional transcriptomics, proteomics, and metabolomics is knowledge about the appropriate tissue/cell or surrogate to evaluate and validated biomarkers that reflect changes in each. As the era of molecular nutrition grows, a greater understanding about the role of foods and their components on cancer risk and tumor behavior will surely unfold. Such information will be critical in the development of effective preemptive approaches to reduce the cancer burden. C1 NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Milner, JA (reprint author), NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH,Dept Hlth & Human Serv, 6130 Execut Blvd,Suite 3164, Bethesda, MD 20892 USA. EM milnerj@mail.nih.gov NR 65 TC 31 Z9 31 U1 3 U2 15 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 2006 VL 56 IS 2 BP 216 EP 224 DI 10.1207/s15327914nc5602_13 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 146BG UT WOS:000244908900013 PM 17474868 ER PT J AU Goodman, M Bostick, RM Ward, KC Terry, PD van Gils, CH Taylor, JA Mandel, JS AF Goodman, Michael Bostick, Roberd M. Ward, Kevin C. Terry, Paul D. van Gils, Carla H. Taylor, Jack A. Mandel, Jack S. TI Lycopene intake and prostate cancer risk: Effect modification by plasma antioxidants and the XRCC1 genotype SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DNA-REPAIR GENES; BETA-CAROTENE; TOMATO PRODUCTS; FRUIT CONSUMPTION; ALPHA-TOCOPHEROL; BLADDER-CANCER; POLYMORPHISMS; DIET; SUSCEPTIBILITY AB Lycopene has been associated with reduced prostate cancer risk, although the results ofepidemiological studies have varied We hypothesize that an effect of lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food-frequency questionnaire to assess lycopene intake in a case-control study of prostate cancer in North Carolina. Plasma a-tocopherol and P-carotene levels were measured using high-performance liquid chromatography. XRCC1 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism. The final dataset included 77 cases and 174 controls with complete questionnaires, genotyping, and plasma analyses. Among men with the Arg/Arg genotype at codon 399, odds ratios (M)for prostate cancer risk associated with medium (732-1,529 mu g/day) and high (> 1, 529 mu g/day) lycopene intake were 0.59 (95% confidence interval = 0.23-1.50) and 0.21 (0.06-0.71), respectively (P-trend < 0.01). Similar analyses for persons with Arg/Gln or Gln/Gln genotypes produced null results. Above-median (1,048 mu g/day) lycopene intake combined with above-median levels of a-tocopherol and beta-carotene was associated with an OR of 0.11 (0.02-0.65) among men with the Arg/Arg genotype but not those with at least one Gln allele (P-interaction 0.01). Although limited by small sample size, these findings indicate that the association between lycopene and prostate cancer is complex and may be modified by other antioxidants and by XRCC1 genotype. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. NIEHS, Mol Carcinogenesis Lab, Mol & Genet Epidemiol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Goodman, M (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, 1518 Clifton Rd,NE, Atlanta, GA 30322 USA. EM mgoodm2@sph.emory.edu OI taylor, jack/0000-0001-5303-6398 NR 57 TC 24 Z9 24 U1 0 U2 0 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 2006 VL 55 IS 1 BP 13 EP 20 DI 10.1207/s15327914nc5501_2 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 086GO UT WOS:000240662000002 PM 16965236 ER PT J AU Whiteside, MA Piyathilake, CJ Bushell, TM Johanning, GL AF Whiteside, Martin A. Piyathilake, Chandrika J. Bushell, Tamara M. Johanning, Gary L. TI Intrinsic cisplatin resistance in lung and ovarian cancer cells propagating in medium acutely depleted of folate SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID DEOXYNUCLEOTIDE POOL IMBALANCE; CILIARY NEUROTROPHIC FACTOR; FOLIC-ACID FORTIFICATION; IN-VITRO; FOOD FORTIFICATION; DIETARY-FOLATE; SERUM FOLATE; EXPRESSION; APOPTOSIS; LINES AB Many tumors develop intrinsic and/or acquired resistance to cisplatin. The purpose of the present study was to examine the influence of acute extracellular folate depletion prior to cisplatin treatment on the development of intrinsic cisplatin resistance. Lung and ovarian cancer cells were propagated in medium acutely depleted of folate and subsequently treated with cisplatin. The IC50 level for cisplatin, cell viability, cell proliferation, and global DNA methylation were determined. Gene expression profiling was performed using the Atlas Cancer 1.2 Array. Acute extracellular folate depletion resulted in the development of intrinsic cisplatin resistance. Cells propagating in medium acutely depleted of folate had a survival advantage compared to control cells when exposed to cisplatin, and thymidine supplenzentation did not reverse the intrinsic cisplatin resistance. cDNA microarray analysis revealed some novel genes associated with the development of intrinsic cisplatin resistance. Our report is the first to demonstrate that acute extracellular folate depletion results in intrinsic cisplatin resistance. If these results are confirmed by in vivo human studies, it would suggest that the folate status of the recipient of cisplatin might have an impact on response to that chemotherapeutic agent. C1 Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX 78602 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. RP Johanning, GL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, 650 Cool Water Dr, Bastrop, TX 78602 USA. EM gljohann@mdanderson.org FU NCI NIH HHS [R21 CA105434, R03 CA99100]; NIDDK NIH HHS [P30 DK56336] NR 50 TC 5 Z9 6 U1 1 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 2006 VL 54 IS 2 BP 274 EP 284 DI 10.1207/s15327914nc5402_14 PG 11 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 101LP UT WOS:000241742600014 PM 16898872 ER PT S AU Knowler, WC AF Knowler, William C. BE Bantle, JP Slama, G TI Optimal diet for glycemia and lipids SO Nutritional Management of Diabetes Mellitus and Dysmetabolic Syndrome SE NESTLE NUTRITION WORKSHOP SERIES: CLINICAL & PERFORMANCE PROGRAM LA English DT Proceedings Paper CT 11th Nestle Nutrition Workshop CY OCT 30-NOV 02, 2005 CL Hangzhou, PEOPLES R CHINA ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; COST-EFFECTIVENESS; DIABETES-MELLITUS; PREVENTION; RISK; METFORMIN; REDUCTION; BEVERAGES; OBESITY AB Concentrations of glucose and lipids in the blood have important health implications and are influenced by dietary intake. Dietary intake and energy expenditure regulate body weight, which is also an important determinant of health. Thus it would be important to determine the optimal diet for affecting blood glucose and lipids and body weight. Many professional health organizations in different countries have made dietary recommendations that include caloric restriction when needed to prevent or reverse over-weight or obesity, limitation of saturated and trans fat, and emphasis on fruits and vegetables. These professional groups have not recommended extremely low carbohydrate or extremely low fat diets, despite much popular interest and recent research in these approaches. In several clinical trials, diet and exercise interventions prevented or delayed the development of type-2 diabetes. These trials showed the value of diet interventions, but did not attempt to determine which dietary approach was optimal. Clinical trials attempting to determine the optimal diet suffer from small sample sizes, short follow-up, and poor follow-up of participants. Therefore, the optimal balance between the total fat and carbohydrate contents and the optimal types of fats and carbohydrates remain unknown. Copyright (c) 2006 Nestec Ltd. C1 NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ 85014 USA. RP Knowler, WC (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. NR 20 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1422-7584 BN 3-8055-8095-9 J9 NES NUTR WS PY 2006 VL 11 BP 97 EP 105 DI 10.1159/000094428 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA BFB52 UT WOS:000240796200008 PM 16820734 ER PT J AU Kimm, SYS Glynn, NW Obarzanek, E Aston, CE Daniels, SR AF Kimm, SYS Glynn, NW Obarzanek, E Aston, CE Daniels, SR TI Racial differences in correlates of misreporting of energy intake in adolescent females SO OBESITY LA English DT Article DE under-reporting; doubly labeled water; adiposity; BMI; ethnicity ID DOUBLY LABELED WATER; FOOD-FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; BODY-MASS INDEX; REPORTED ENERGY; 24-HOUR RECALL; DIETARY-INTAKE; ELDERLY-WOMEN; NHLBI GROWTH AB Objective: To determine the extent of misreporting of energy intake (EI) and its anthropometric, demographic, and psychosocial correlates in a bi-racial cohort of young women. Research Methods and Procedures: This was a cross-sectional study of 60 black and 60 white young women, 18 to 21 years old, enrolled in a longitudinal study. Total energy expenditure was assessed using doubly labeled water. Self-reported EI was obtained from 3-day food records. BMI was computed from height and weight. Fat mass was assessed by DXA. Multivariate analyses examined racial differences on the extent of misreporting and its effect on other potential correlates of misreporting. Race-specific step-wise linear regression analysis was performed to examine the effect of BMI, parental education, and drive for thinness on misreporting of EI. Results: More white women tended to under-report EI than black women (22% vs. 13%, P = 0.07). In black women, under-reporting was significantly (p = 0.01), associated with drive for thinness score but was only marginally (p = 0.1) associated with BMI. Each point increase in drive for thinness score was associated with under-reporting by 40 kcal/d. In white women, under-reporting was significantly (p = 0.03) associated with higher parental education by 440 kcal/d and also only marginally (p = 0.09) with BMI. Discussion: This tendency for under-reporting of EI limits the use of self-reported EI in studying energy balance in free-living subjects. Most black and almost all white women in their late teens significantly under-reported their EI, whereas under-reporting was not as evident among lean young black women. C1 Univ Pittsburgh, Sch Med, Dept Family Med, Pittsburgh, PA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. Cincinnati Childrens Hosp, Div Cardiol, Cincinnati, OH USA. RP Kimm, SYS (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Internal Med Epidemiol, MSC 10 5550, Albuquerque, NM 87131 USA. EM skimm@salud.unm.edu OI Glynn, Nancy/0000-0003-2265-0162 FU NHLBI NIH HHS [U01-HL489843, R01-HL52911, R01-HL54886, U01-HL48941] NR 67 TC 14 Z9 14 U1 2 U2 4 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD JAN PY 2006 VL 14 IS 1 BP 156 EP 164 DI 10.1038/oby.2006.19 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 055JY UT WOS:000238447800019 PM 16493134 ER PT J AU Offenbacher, S Boggess, KA Murtha, AP Jared, HL Lieff, S McKaig, RG Mauriello, SM Moss, KL Beck, JD AF Offenbacher, S Boggess, KA Murtha, AP Jared, HL Lieff, S McKaig, RG Mauriello, SM Moss, KL Beck, JD TI Progressive periodontal disease and risk of very preterm delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; PREGNANT-WOMEN; INFECTION; MECHANISMS; INFANTS AB OBJECTIVE: The goal was to estimate whether maternal periodontal disease was predictive of preterm (less than 37 weeks) or very preterm (less than 32 weeks) births. METHODS: A prospective study of obstetric outcomes, entitled Oral Conditions and Pregnancy (OCAP), was conducted with 1,020 pregnant women who received both an antepartum and postpartum periodontal examination. Predictive models were developed to estimate whether maternal exposure to either periodontal disease at enrollment (less than 26 weeks) and/or periodontal disease progression during pregnancy, as determined by comparing postpartum with antepartum status, were predictive of preterm or very preterm births, adjusting for risk factors including previous preterm delivery, race, smoking, social domain variables, and other infections. RESULTS: Incidence of preterm birth was 11.2% among periodontally healthy women, compared with 28.6% in women with moderate-severe periodontal disease (adjusted risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1-2.3). Antepartum moderate-severe periodontal disease was associated with an increased incidence of spontaneous preterm births (15.2% versus 24.9%, adjusted RR 2.0, 95% CI 1.2-3.2). Similarly, the unadjusted rate of very preterm delivery was 6.4% among women with periodontal disease progression, significantly higher than the 1.8% rate among women without disease progression (adjusted RR 2.4, 95% CI 1.1-5.2). CONCLUSION: The OCAP study demonstrates that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births. Furthermore, perioclontal disease progression during pregnancy was a predictor of the more severe adverse pregnancy outcome of very preterm birth, independently of traditional obstetric, periodontal, and social domain risk factors. C1 Univ N Carolina, Sch Dent, Ctr Oral & System Dis, Dept Periodontol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Dent, Ctr Oral & System Dis, Dept Dent Ecol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA. Duke Univ, Dept Obstet & Gynecol, Durham, NC 27710 USA. NIAID, Bethesda, MD 20892 USA. RP Offenbacher, S (reprint author), Univ N Carolina, Sch Dent, Ctr Oral & System Dis, Dept Periodontol, CB 7544,DRC Room 222, Chapel Hill, NC 27599 USA. EM steve_offenbacher@dentistry.unc.edu FU NCRR NIH HHS [M01-RR0046]; NIDCR NIH HHS [P-60-DE-13079, R01-DE-12453, T-32-DE07310] NR 24 TC 156 Z9 175 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2006 VL 107 IS 1 BP 29 EP 36 DI 10.1097/01.AOG.0000190212.87012.96 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 997ZN UT WOS:000234287700006 PM 16394036 ER PT J AU Reddy, UM Mennuti, MT AF Reddy, UM Mennuti, MT TI Incorporating First-Trimester Down Syndrome Studies into Prenatal Screening - Executive Summary of the National Institute of Child Health and Human Development Workshop SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FETAL NUCHAL TRANSLUCENCY; 1ST TRIMESTER; SERUM MARKERS; 2ND TRIMESTER; UNITED-STATES; ULTRASOUND; ABNORMALITIES; PREGNANCY; DIAGNOSIS; AGE AB The National Institute of Child Health and Human Development (NICHD), the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists (ACOG), cosponsored a workshop on December 16-17, 2004, to discuss the evidence for first-trimester Down syndrome screening and to explore the effects of combining first- and second-trimester screening, given the results of recent U.S. trials. The experts evaluated the evidence for offering first-trimester screening to provide individual risk assessment for Down syndrome. First-trimester screening has been demonstrated to provide efficient Down syndrome risk assessment, with a detection rate of 84% (95% confidence interval 80-87%), which is clinically comparable to the second-trimester quadruple screen at a fixed false-positive rate of 5%. The participants at the workshop concluded that at this time there is sufficient evidence to support implementing first-trimester Down syndrome risk assessment in obstetric practice in the United States, provided that certain requirements can be met. These requirements include training and quality control standards for first-trimester nuchal translucency measurement and laboratory assays, access to chorionic villus sampling, and appropriate counseling regarding screening options. C1 NICHHD, Pregnancy & Perinatol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA USA. RP Reddy, UM (reprint author), 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 22 TC 26 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2006 VL 107 IS 1 BP 167 EP 173 DI 10.1097/01.AOG.0000194186.34664.a9 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 997ZN UT WOS:000234287700025 PM 16394055 ER PT J AU Blair, A AF Blair, A TI Occupational exposures and non-Hodgkin lymphoma: where do we stand? SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Execut Plaza S,Room 8118, Bethesda, MD 20892 USA. EM blaira@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010120-10] NR 8 TC 4 Z9 4 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JAN PY 2006 VL 63 IS 1 BP 1 EP 2 DI 10.1136/oem.2005.023978 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 993YF UT WOS:000233995100001 PM 16361397 ER PT J AU Nesterova, MV AF Nesterova, Maria V. TI Yoon Cho-Chung, MD 1932-2006 - In memoriam SO OLIGONUCLEOTIDES LA English DT Biographical-Item C1 NCI, CCR, Basic Res Lab, Cellular Biol Sect, Bethesda, MD 20892 USA. RP Nesterova, MV (reprint author), NCI, CCR, Basic Res Lab, Cellular Biol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-4576 J9 OLIGONUCLEOTIDES JI Oligonucleotides PY 2006 VL 16 IS 3 BP IX EP IX DI 10.1089/oli.2006.16.ix PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 084UA UT WOS:000240558700001 ER PT J AU Qiao, W Li, AG Owens, P Xu, X Wang, XJ Deng, CX AF Qiao, W Li, AG Owens, P Xu, X Wang, XJ Deng, CX TI Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin SO ONCOGENE LA English DT Article DE squamous cell carcinoma; hair follicle cycle; Pten; AKT; cyclin D1 ID TUMOR-SUPPRESSOR SMAD4/DPC4; TGF-BETA RECEPTOR; TRANSGENIC MICE; CHEMICAL CARCINOGENESIS; JUVENILE POLYPOSIS; CYCLE ARREST; EXPRESSION; GENE; DIFFERENTIATION; DELETION AB Smad4 is the common mediator for TGF beta signals, which play important functions in many biological processes. To study the role of Smad4 in skin development and epidermal tumorigenesis, we disrupted this gene in skin using the Cre-loxP approach. We showed that absence of Smad4 blocked hair follicle differentiation and cycling, leading to a progressive hair loss of mutant (MT) mice. MT hair follicles exhibited diminished expression of Lef1, and increased proliferative cells in the outer root sheath. Additionally, the skin of MT mice exhibited increased proliferation of basal keratinocytes and epidermal hyperplasia. Furthermore, we provide evidence that the absence of Smad4 resulted in a block of both TGFb and bone morphogenetic protein (BMP) signaling pathways, including p21, a well-known cyclin-dependent kinase inhibitor. Consequently, all MT mice developed spontaneous malignant skin tumors from 3 months to 13 months of age. The majority of tumors are malignant squamous cell carcinomas. A most notable finding is that tumorigenesis is accompanied by inactivation of phosphatase and tensin homolog deleted on chromosome 10 (Pten), activation of AKT, fast proliferation and nuclear accumulation of cyclin D1. These observations revealed the essential functions of Smad4-mediated signals in repressing skin tumor formation through the TGF beta/BMP pathway, which interacts with the Pten signaling pathway. C1 Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97239 USA. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. RP Wang, XJ (reprint author), Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97239 USA. EM wangxiao@ohsu.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [CA87849]; NIAMS NIH HHS [AR47898] NR 44 TC 58 Z9 64 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 2 BP 207 EP 217 DI 10.1038/sj.onc.1209029 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 002AK UT WOS:000234583600005 PM 16170355 ER PT J AU Chen, A Xu, J Johnson, AC AF Chen, A Xu, J Johnson, AC TI Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1 SO ONCOGENE LA English DT Article DE colon cancer; receptors; phyto-chemical; gene expression; chemo-prevention ID NF-KAPPA-B; SERUM RESPONSE ELEMENTS; TERNARY COMPLEX FACTORS; ACTIVATION; PHOSPHORYLATION; DIFFERENTIATION; MALIGNANCIES; CONTRIBUTES; INDUCTION; APOPTOSIS AB High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and site-directed mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer. C1 Louisiana State Univ, HSC, Dept Pathol, Shreveport, LA 71130 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cellular Biol & Anat, Shreveport, LA USA. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD USA. RP Chen, A (reprint author), Louisiana State Univ, HSC, Dept Pathol, BRI F8-20,1501 Kings Hwy, Shreveport, LA 71130 USA. EM achen@lsuhsc.edu FU NIDDK NIH HHS [DK 47995] NR 48 TC 150 Z9 162 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 2 BP 278 EP 287 DI 10.1038/sj.onc.1209019 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 002AK UT WOS:000234583600012 PM 16170359 ER PT J AU Park, HU Jeong, SJ Jeong, JH Chung, JH Brady, JN AF Park, HU Jeong, SJ Jeong, JH Chung, JH Brady, JN TI Human T-cell leukemia virus type 1 Tax attenuates gamma-irradiation-induced apoptosis through physical interaction with Chk2 SO ONCOGENE LA English DT Article DE HTLV-1 Tax; Chk2; interaction; attenuation; apoptosis ID NF-KAPPA-B; PRIMARY HUMAN-LYMPHOCYTES; DNA-DAMAGE-RESPONSE; CHECKPOINT KINASE; TUMOR-SUPPRESSOR; P53-MEDIATED TRANSACTIVATION; TRANSCRIPTIONAL ACTIVITY; PHASE PROGRESSION; P53 INACTIVATION; GENE-EXPRESSION AB Checkpoint kinase 2 (Chk2) is known to mediate diverse cellular responses to genotoxic stress. The fundamental role of Chk2 is to regulate the network of genomesurveillance pathways that coordinate cell-cycle progression withDN A repair and cell survival or death. Defects in Chk2 contribute to the development of both hereditary and sporadic human cancers. We now present evidence that the human T-cell leukemia virus type-1 (HTLV-1) Tax protein directly interacts with Chk2 and the kinase activity of Chk2 is inhibited by Tax. The physical interaction of Chk2 and Tax was observed by co-immunoprecipitation assays in HTLV-1-infected T cells (C81) as well as GST pull-down assays using purified proteins. Binding and kinase activity inhibition studies with Tax deletion mutants indicated that at least two domains of Tax mediate the interaction with Chk2. We have analysed the functional consequence of de novo expression of Tax upon the cellular DNA-damage-induced apoptosis, which is mediated by Chk2. Using transient transfection and TUNEL assay, we found that cirradiation-induced apoptosis was decreased in 293T and HCT-116 (p53 (-/-)) cells expressing HTLV-1 Tax. Our studies demonstrate an important potential target of Tax in cellular transformation. C1 NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bldg 41-B201,41 Medlars Dr,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov FU Intramural NIH HHS NR 59 TC 26 Z9 26 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 3 BP 438 EP 447 DI 10.1038/sj.onc.1209059 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 003WY UT WOS:000234714100012 PM 16158050 ER PT J AU Zhou, L Isenberg, JS Cao, Z Roberts, DD AF Zhou, L Isenberg, JS Cao, Z Roberts, DD TI Type I collagen is a molecular target for inhibition of angiogenesis by endogenous thrombospondin-1 SO ONCOGENE LA English DT Article DE 3D culture; endothelial cells; angiogenesis inhibitors; collagens ID GROWTH-FACTOR-BETA; ENDOTHELIAL-CELL RESPONSES; TUMOR-GROWTH; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; CAPILLARY MORPHOGENESIS; ACTIVATION; VIVO; MECHANISMS; APOPTOSIS AB Three-dimensional explant cultures of muscle tissue were used to characterize secreted proteins regulated by endogenous levels of the angiogenesis modulator thrombospondin (TSP)-1. Explants from TSP1 null mice exhibit enhanced neovascularization associated with increased endothelial outgrowth but decreased outgrowth of perivascular smooth muscle cells. The absence of endogenous TSP1 did not diminish activation of latent transforming growth factor-beta and moderately decreased matrix metal-loproteinase levels. However, significant changes in other secreted proteins were observed. Endogenous TSP1 decreased mRNA levels for collagens I alpha 1, I alpha 2, and III alpha 1 and laminin alpha 4 and increased collagen IV alpha 1 mRNA expression. Endogenous TSP1 also decreased the level of type I collagen protein produced by the vascular out-growths. Collagens Ia1, Ia2, and IIIa1 are known tumor endothelial markers, suggesting that TSP1 coordinately regulates a set of extracellular matrix genes that reverse the angiogenic switch. Suppression of collagen Ia1 or Ia2 mRNAs using antisense morpholinos inhibited outgrowth in TSP1 null explants and proliferation of TSP1 null endothelial cells, indicating that type I collagen synthesis is limiting for this neovascularization response. C1 NCI, Biochem Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Roberts, DD (reprint author), NCI, Biochem Pathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS NR 66 TC 18 Z9 19 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 4 BP 536 EP 545 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 006KW UT WOS:000234897400005 PM 16247480 ER PT J AU Hara, T Abe, M Inoue, H Yu, LR Veenstra, TD Kang, YH Lee, KS Miki, T AF Hara, T Abe, M Inoue, H Yu, LR Veenstra, TD Kang, YH Lee, KS Miki, T TI Cytokinesis regulator ECT2 changes its conformation through phosphorylation at Thr-341 in G2/M phase SO ONCOGENE LA English DT Article DE exchange factor; Rho GTPases; Cdk1; interacting proteins; cell division ID EXCHANGE FACTOR ECT2; RHOA; SPINDLE; MIDBODY; DOMAINS; GTPASES; CDK1; CDC2 AB The Rho activator ECT2 functions as a key regulator in cytokinesis. ECT2 is phosphorylated during G2/M phase, but the physiological significance of this event is not well known. In this study, we show that phosphorylation of ECT2 at threonine-341 (T341) affects the autoregulatory mechanism of ECT2. In G2/M phase, ECT2 was phosphorylated at T341 most likely by Cyclin B/Cyclindependent kinase 1 (Cdk1), and then dephosphorylated before cytokinesis. Depletion of ECT2 by RNA interference (RNAi) efficiently induced multinucleate cells. Expression of the phospho-deficient mutant of ECT2 at T341 suppressed the multinucleation induced by RNAi to ECT2, indicating that ECT2 is biologically active even when it is not phosphorylated at T341. However, the phospho-mimic mutation at T341 weakly stimulates the catalytic activity of ECT2 as detected by serum response element reporter gene assays. As T341 is located at the hinge region of the N-terminal regulatory domain and C-terminal catalytic domain, phosphorylation of T341 may help accessing downstream signaling molecules to further activate ECT2. We found that the phospho-mimic mutation T341D increases binding with itself or the N-terminal half of ECT2. These results suggest a conformational change of ECT2 upon phosphorylation at T341. Therefore, ECT2 activity might be regulated by the phosphorylation status of T341. We propose that T341 phosphorylation by Cyclin B/Cdk1 could be a trigger for further activation of ECT2. C1 NCI, Mol Tumor Biol Sect, Cell Biol Lab, Bethesda, MD 20892 USA. NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Mol Tumor Biol Sect, Cell Biol Lab, Bldg 37,Room 2144,37 Convent Dr MSC 4256, Bethesda, MD 20892 USA. EM toru@helix.nih.gov FU Intramural NIH HHS NR 26 TC 33 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 4 BP 566 EP 578 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 006KW UT WOS:000234897400008 PM 16170345 ER PT J AU Tsai, MH Chen, X Chandramouli, GVR Chen, Y Yan, H Zhao, S Keng, P Liber, HL Coleman, CN Mitchell, JB Chuang, EY AF Tsai, MH Chen, X Chandramouli, GVR Chen, Y Yan, H Zhao, S Keng, P Liber, HL Coleman, CN Mitchell, JB Chuang, EY TI Transcriptional responses to ionizing radiation reveal that p53R2 protects against radiation-induced mutagenesis in human lymphoblastoid cells SO ONCOGENE LA English DT Article DE microarray; radiation; p53R2; TK6 ID NF-KAPPA-B; RIBONUCLEOTIDE REDUCTASE GENE; NUCLEOTIDE EXCISION-REPAIR; THYMIDINE KINASE LOCUS; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; CYCLE CHECKPOINT; MAMMALIAN-CELLS; CANCER CELLS; APOPTOSIS AB The p53 protein has been implicated in multiple cellular responses related to DNA damage. Alterations in any of these cellular responses could be related to increased genomic instability. Our previous study has shown that mutations in p53 lead to hypermutability to ionizing radiation. To investigate further how p53 is involved in regulating mutational processes, we used 8K cDNA microarrays to compare the patterns of gene expression among three closely related human cell lines with different p53 status including TK6 (wild-type p53), NH32 (p53null), and WTK1 (mutant p53). Total RNA samples were collected at 1, 3, 6, 9, and 24 h after 10 Gy gamma-irradiation. Template-based clustering analysis of the gene expression over the time course showed that 464 genes are either up or downregulated by at least twofold following radiation treatment. In addition, cluster analyses of gene expression profiles among these three cell lines revealed distinct patterns. In TK6, 165 genes were upregulated, while 36 genes were downregulated. In contrast, in WTK1 75 genes were upregulated and 12 genes were downregulated. In NH32, only 54 genes were upregulated. Furthermore, we found several genes associated with DNA repair namely p53R2, DDB2, XPC, PCNA, BTG2, and MSH2 that were highly induced in TK6 compared to WTK1 and NH32. p53R2, which is regulated by the tumor suppressor p53, is a small subunit of ribonucleotide reductase. To determine whether it is involved in radiation-induced mutagenesis, p53R2 protein was inhibited by siRNA in TK6 cells and followed by 2Gy radiation. The background mutation frequencies at the TK locus of siRNA-transfected TK6 cells were about three times higher than those seen in TK6 cells. The mutation frequencies of siRNA-transfected TK6 cells after 2 Gy radiation were significantly higher than the irradiated TK6 cells without p53R2 knock down. These results indicate that p53R2 was induced by p53 protein and is involved in protecting against radiation-induced mutagenesis. C1 NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. RP Chuang, EY (reprint author), NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bldg 10,Room B3-B69, Bethesda, MD 20892 USA. EM chuange@mail.nih.gov NR 48 TC 28 Z9 28 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 2006 VL 25 IS 4 BP 622 EP 632 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 006KW UT WOS:000234897400013 PM 16247478 ER PT J AU Goldman, ML Denduluri, N Berman, AW Sausville, R Guadagnini, JP Kleiner, DE Brahim, JS Swain, SM AF Goldman, Matthew L. Denduluri, Neelima Berman, Arlene W. Sausville, Rebecca Guadagnini, Jean-Pierre Kleiner, David E. Brahim, Jaime S. Swain, Sandra M. TI A novel case of bisphosphonate-related osteonecrosis of the torus palatinus in a patient with metastatic breast cancer SO ONCOLOGY LA English DT Article DE zoledronic acid; bisphosphonate toxicity; maxillary exostosis; jaw osteonecrosis; torus palatinus ID MULTIPLE-MYELOMA; RISK-FACTORS; BONE; JAW AB Bisphosphonates administered orally and intravenously are used for a variety of endocrine and oncologic indications. Long- term intravenous use of bisphosphonates has been shown to cause osteonecrosis of the jaw. We report a case in which a 58- year- old woman with metastatic breast cancer received 18 doses of 4 mg intravenous zoledronic acid over a period of 16 months and developed a region of osteonecrosis on the posterior edge of a large, lobular torus palatinus. Torus palatinus, a type of maxillary exostosis, is common among postmenopausal women, and is vulnerable to blunt trauma that could predispose to osteonecrosis. Sequestrum of dead bone was removed and the site healed within 4 weeks. This case demonstrates that patients with a torus palatinus may be at high risk for osteonecrosis, and reinforces the need for good oral hygiene and frequent dental examination while receiving bisphosphonate therapy. C1 NCI, Natl Inst Hlth, Ctr Canc Res, Med Oncol Branch,Breast Canct Sect, Bethesda, MD 20889 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Natl Inst Hlth, Dent Consult Serv, Bethesda, MD USA. Natl Inst Hlth, Natl Inst Dental & Craniofacial Res, Bethesda, MD USA. RP Swain, SM (reprint author), NCI, Natl Inst Hlth, Ctr Canc Res, Med Oncol Branch,Breast Canct Sect, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453; Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 11 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2006 VL 71 IS 3-4 BP 306 EP 308 DI 10.1159/000106451 PG 3 WC Oncology SC Oncology GA 203QW UT WOS:000248990100025 PM 17657174 ER PT J AU Alfano, CM McGregor, BA Kuniyuki, A Reeve, BB Bowen, DJ Smith, AW Baumgartner, KB Bernstein, L Ballard-Barbash, R Malone, KE Ganz, PA McTiernan, A AF Alfano, Catherine M. McGregor, Bonnie A. Kuniyuki, Alan Reeve, Bryce B. Bowen, Deborah J. Smith, Ashley Wilder Baumgartner, Kathy B. Bernstein, Leslie Ballard-Barbash, Rachel Malone, Kathleen E. Ganz, Patricia A. McTiernan, Anne TI Psychometric evaluation of the brief cancer impact assessment among breast cancer survivors SO ONCOLOGY LA English DT Article DE cancer survivors; factor analysis; impact of cancer; psychometric testing; quality of life ID QUALITY-OF-LIFE; LONG-TERM; WOMEN; STRESS; VALIDATION; MASTECTOMY; ADJUSTMENT; HEALTH; INDEX AB objectives:The increasing number of cancer survivors brings greater attention to the biopsychosocial impact of surviving cancer. Instruments exist that measure quality of life (QOL), symptoms, and specific types of functioning after cancer; however, a reliable and valid assessment of the perceived impact of cancer (IOC) on the life plans and activities of cancer survivors has been missing. This study evaluated the psychometric properties of the 16-item Brief Cancer Impact Assessment (BCIA). Methods: Factor analysis with Promax oblique rotation established the factor structure of the BCIA in 783 ethnically diverse breast cancer survivors, >= 2 years after diagnosis. Construct validity was assessed by comparing factor-based scale means by demographic and treatment characteristics, and correlating scales with psychosocial and health-related QOL scales. Results: Factor analysis revealed four factors measuring the IOC on caregiving and finances, exercise and diet behaviors, social and emotional functioning, and religiosity. Scale scores differed by demographic and treatment characteristics according to expectations, and the pattern of correlations with psychosocial and health-related QOL generally supported the construct validity of the scales. Conclusion: Including the BCIA with measures of QOL, symptoms, and functioning will allow researchers to gain a more comprehensive assessment of the biopsychosocial IOC in survivors. Copyright (c) 2006 S. Karger AG, Basel C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ New Mexico, Hlth Sci Ctr, Canc Res & Treatment Ctr, Dept Internal Med, Albuquerque, NM 87131 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90034 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B402,POB 19024, Seattle, WA 98109 USA. EM amctiern@fhcrc.org FU NCI NIH HHS [N01 PC035138-22, R25 CA092408] NR 35 TC 14 Z9 14 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2006 VL 70 IS 3 BP 190 EP 202 DI 10.1159/000094320 PG 13 WC Oncology SC Oncology GA 068QU UT WOS:000239390300006 PM 16809938 ER PT J AU Krueger, KE AF Krueger, Karl E. TI The potential of serum proteomics for detection of cancer: Promise or only hope? SO ONKOLOGIE LA English DT Editorial Material ID OVARIAN-CANCER; PROSTATE-CANCER; PATTERNS; REPRODUCIBILITY; DIAGNOSIS; PEPTIDOME C1 NCI, Canc Biomarkers Res Ctr, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Krueger, KE (reprint author), NCI, Canc Biomarkers Res Ctr, Div Canc Prevent, NIH, 6130 Execut Blvd,Suite 3147, Bethesda, MD 20892 USA. EM kruegerk@mail.nih.gov NR 14 TC 2 Z9 3 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PY 2006 VL 29 IS 11 BP 498 EP 499 DI 10.1159/000096163 PG 2 GA 101XJ UT WOS:000241774300001 PM 17068383 ER PT B AU Zou, J Le, D Thoma, GR AF Zou, Jie Le, Daniel Thoma, George R. GP IEEE TI Combining DOM tree and geometric layout analysis for Online medical journal article segmentation SO Opening Information Horizons LA English DT Proceedings Paper CT 6th ACM/IEEE Joint Conference on Digital Libraries (JCDL) CY JUN 11-15, 2006 CL Chapel Hill, NC SP ACM SIGIR, IEEE TC DL DE document object model (DOM); document layout analysis; HTML document segmentation; web information retrieval ID DOCUMENT IMAGE-ANALYSIS AB We describe an HTML web page segmentation algorithm, which is applied to segment online medical journal articles (regular HTML and PDF-Converted-HTML files). The web page content is modeled by a zone tree structure based primarily on the geometric layout of the web page. For a given journal article, a zone tree is generated by combining DOM tree analysis and recursive X-Y cut algorithm. Combining with other visual cues, such as background color, font size, font color and so on, the page is segmented into homogeneous regions. Evaluation is conducted with 104 articles from 11 Journals. Out of 9726 ground-truth zones, 9376 zones are correctly segmented, for an accuracy of 96.40%. Segmenting the entire web page into zones can significantly expedite and increase the accuracy of the subsequent information retrieval steps. C1 Natl Lib Med, Lister Hill Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU ASSOC COMPUTING MACHINERY PI NEW YORK PA 1515 BROADWAY, NEW YORK, NY 10036-9998 USA BN 1-59593-354-9 PY 2006 BP 119 EP 128 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BEQ50 UT WOS:000238914700018 ER PT J AU Shen, DF Wen, R Tuo, JS Bojanowski, CM Chan, CC AF Shen, DF Wen, R Tuo, JS Bojanowski, CM Chan, CC TI Exacerbation of retinal degeneration and choroidal neovascularization induced by subretinal injection of matrigel in CCL2/MCP-1-deficient mice SO OPHTHALMIC RESEARCH LA English DT Article DE neovascularization; retinal degeneration; CCL2; matrigel; macular degeneration, age-related ID MACULAR DEGENERATION; GROWTH-FACTOR; MODEL; PATHOGENESIS; MEMBRANE AB This study presents a mouse model for human age-related macular degeneration (AMD) as characterized by subretinal deposit and choroidal neovascularization. Matrigel, a basement membrane extract, solidifies after implantation in tissue and can stimulate local angiogenesis. This study demonstrates the induction of neovascularization and focal retinal degeneration following subretinal Matrigel injection in mice. In senescent mice, the normal functioning of CC chemokine CCL2/MCP-1 and its receptor CCR2 confers protection against age-related retinal degeneration, a disease that shares many similar features with human AMD. Our data shows that CCL2-deficient mice develop more severe disease as compared to the wild-type controls. These findings suggest that Matrigel subretinal injection could be used to generate AMD-like pathological changes. The data support the previously proposed role of CCL2 in AMD pathogenesis. Copyright (C) 2006 S. Karger AG, Basel. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z01 EY000222-22] NR 17 TC 15 Z9 16 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHAL RES JI Ophthalmic Res. PY 2006 VL 38 IS 2 BP 71 EP 73 DI 10.1159/000090266 PG 3 WC Ophthalmology SC Ophthalmology GA 018YP UT WOS:000235801600004 PM 16352919 ER PT J AU Baccaglini, L Schoenbach, VJ Poole, C McKaig, RG Ibrahim, J Baric, RS Wiesen, C AF Baccaglini, L Schoenbach, VJ Poole, C McKaig, RG Ibrahim, J Baric, RS Wiesen, C TI Association between herpes simplex virus type 1 and Helicobacter pylori in US adolescents SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID UNITED-STATES; SOCIOECONOMIC-STATUS; LIFE-STYLE; INFECTION; EPIDEMIOLOGY; PREVALENCE; CHILDREN; RISK; POPULATION; ADULTS AB Objective. To understand how Helicobacter pylori infection is acquired and the role that herpes simplex virus type 1 (HSV-1) may have, we determined whether an association between HSV and H pylori exists at the individual level and for what reason. Study design. Data were collected from 1,090 participants aged 12-19 years during phase 1 (1988-1991) of the NHANES III. Generalized estimating equations were used to estimate prevalence ratios (PR). Results. The crude overall PR and 95% CI for H pylori seropositivity comparing HSV+ to HSV- individuals was 2.20 (1.69-2.85). In large urban households the PR adjusted for poverty level and race/ethnicity was twice that in small nonurban households (2.27 versus 1.15, respectively). Conclusions. Overall, HSV-1 seropositivity is associated with a higher H pylori seroprevalence. The negligible association found in some strata suggests that shared environmental factors or routes of transmission rather than biologic reasons may be primarily responsible for this association. C1 Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, Div Oral Med, San Antonio, TX 78229 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. NIAID, Epidemiol Branch, DAIDS BSP, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA. Univ N Carolina, Odum Inst, Inst Res Social Sci, Chapel Hill, NC 27515 USA. RP Baccaglini, L (reprint author), Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, Div Oral Med, 7703 Floyd Curl Dr,MC 7919, San Antonio, TX 78229 USA. EM baccaglini@uthscsa.edu FU NIDCR NIH HHS [5T32DE07191]; NIEHS NIH HHS [P30ES10126] NR 24 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JAN PY 2006 VL 101 IS 1 BP 63 EP 69 DI 10.1016/j.tripleo.2004.12.018 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 997ZP UT WOS:000234287900011 PM 16360609 ER PT J AU Ospeck, M Dong, XX Fang, J Iwasa, KH AF Ospeck, Mark Dong, Xiao-Xia Fang, Jie Iwasa, Kuni H. TI Electromotility in outer hair cells: A supporting role for fast potassium conductance SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Article DE outer hair cells; prestin; potassium channel; cochlear amplifier ID GUINEA-PIG COCHLEA; MECHANICAL RESPONSES; MAMMALIAN COCHLEA; AMPLIFIER; CURRENTS; AMPLIFICATION; CAPACITANCE; EXPRESSION; FREQUENCY; MOTILITY AB Motility of outer hair cells underlies the cochlear amplifier, which is critical for the ear's sensitivity and fine tuning. Of the two motile mechanisms present in these cells, electromotility at the lateral wall depends on the receptor potential and thus depends on currents through the cell body. We found that, in the guinea pig cochlea, basal turn outer hair cells have a fast-activating ion current (tau < 0.3 ms at 23 degrees C), which is absent in apical turn cells. This finding is consistent with our previous theoretical analysis that a fast-activating potassium current is required only in the basal turn to counteract the capacitive current and thereby to enhance the effectiveness of electromotility. Thus, our finding is consistent with the functional significance of electromotility. We conjecture therefore that the current reduces the capacitance of the outer hair cell in order to increase hearing bandwidth. Copyright (c) 2006 S. Karger AG, Basel. C1 NIDCD, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), NIDCD, Biophys Sect, NIH, 50th South Dr,MSC 8027, Bethesda, MD 20892 USA. EM iwasa@nih.gov OI Iwasa, Kuni/0000-0002-9397-7704 FU Intramural NIH HHS [Z01 DC000010-14] NR 27 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2006 VL 68 IS 6 BP 373 EP 377 DI 10.1159/000095280 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 100JO UT WOS:000241664500013 PM 17065832 ER PT J AU Ochi, K Derfoul, A Tuan, RS AF Ochi, K Derfoul, A Tuan, RS TI A predominantly articular cartilage-associated gene, SCRG1, is induced by glucocorticoid and stimulates chondrogenesis in vitro SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE SCRG1; articular cartilage; chondrogenesis; dexamethasone; cell proliferation; tissue engineering ID MESENCHYMAL STEM-CELLS; BONE MORPHOGENETIC PROTEIN-2; SCRAPIE-RESPONSIVE GENE; MARROW STROMAL CELLS; PROGENITOR CELLS; DIFFUSION-CHAMBERS; EXPRESSION PROFILES; PRECURSOR CELLS; DIFFERENTIATION; MOUSE AB Objective, Cartilage tissue engineering using multipotential human mesenchymal stem cells (hMSCs) is a promising approach to develop treatment for degenerative joint diseases. A key requirement is that the engineered tissues maintain their hyaline articular cartilage phenotype and not proceed towards hypertrophy. It is noteworthy that osteoarthritic articular cartilage frequently contains limited regions of reparative cartilage, suggesting the presence of bioactive factors with regenerative activity, Based on this idea, we recently performed cDNA microarray analysis to identify genes that are strongly expressed only in articular cartilage and encode secreted gene products, One of the genes that met our criteria was SCRG1. This study aims to analyze SCRG1 function in cartilage development using an in vitro mesenchymal chondrogenesis system. Methods: Full-length SCRG1 cDNA was subcloned into pcDNA5 vector, and transfected into hMSCs and murine C3H10T1/2 mesenchymal cells, placed in pellet cultures and micromass cultures, respectively. The cultures were analyzed by reverse transcription-polymerase chain reaction for the expression of SCRG1 and cartilage marker genes, and by histological staining for cartilage phenotype. Results: Induction of SCRG1 expression was seen during in vitro chondrogenesis, and was dependent on dexamethasone (DEX) known to promote chondrogenesis. Immunohistochemistry revealed that SCRG1 protein was localized to the extracellular matrix, Forced expression of SCRG1 in hMSCs suppressed their proliferation, and stimulated chondrogenesis in C3H10T1/2 cells, confirmed by reduced collagen type and elevated collagen type IIB expression. Conclusion: These results suggest that SCRG1 is involved in cell growth suppression and differentiation during DEX-dependent chondrogenesis. SCRG1 may be of utility in gene-mediated cartilage tissue engineering. (C) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd, All rights reserved. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 S Dri,Room 1523, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU NIAMS NIH HHS [Z01AR41131] NR 56 TC 17 Z9 18 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD JAN PY 2006 VL 14 IS 1 BP 30 EP 38 DI 10.1016/j.joca.2005.07.015 PG 9 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 007II UT WOS:000234961900004 PM 16188469 ER PT J AU Rubin, RJ AF Rubin, Robert J. BE Byers, N Williams, G TI Vera Cooper Rubin (1928-) SO OUT OF THE SHADOWS: CONTRIBUTIONS OF TWENTIETH-CENTURY WOMEN TO PHYSICS LA English DT Biographical-Item; Book Chapter C1 NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Rubin, RJ (reprint author), NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-82197-1 PY 2006 BP 343 EP 354 PG 12 WC History & Philosophy Of Science; Physics, Multidisciplinary SC History & Philosophy of Science; Physics GA BXL63 UT WOS:000296295500033 ER PT J AU Vahratian, A Troendle, JF Siega-Riz, AM Zhang, J AF Vahratian, A Troendle, JF Siega-Riz, AM Zhang, J TI Methodological challenges in studying labour progression in contemporary practice SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE cervical dilation; length of labour ID NULLIPAROUS WOMEN; GRAPHICOSTATISTICAL ANALYSIS; INDUCTION; LENGTH; CURVE; TERM AB In the 1950s, Emanuel Friedman described the first comprehensive method of evaluating labour in clinical practice. In this landmark work, Friedman described the relationship between the duration of labour and cervical dilation as a sigmoid curve and outlined a tool for following labour progression and for identifying abnormal labour. His definitions of labour protraction and arrest continue to be applied in contemporary obstetric practice, although there have been considerable changes since in the clinical management of labour and delivery. This paper provides an overview of Friedman's work, addresses various methodological challenges in studying labour progression, and describes the utility of more advanced statistical methods for studying labour progression, such as survival analysis, compared with other approaches. Additional research that utilises and refines such methods will provide greater insight into labour progression and may assist in updating the diagnostic criteria for labour protraction and arrest disorders in contemporary obstetric practice. Moreover, such detailed information could have important clinical implications towards reducing the rate of primary caesarean delivery in the United States. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Maternal & Child Hlth, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Nutr, Chapel Hill, NC USA. Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. RP Vahratian, A (reprint author), Univ Michigan, Womens Hosp L4000, Dept Obstet & Gynecol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM amv@med.umich.edu RI Vahratian, Anjel/A-1182-2011 FU Intramural NIH HHS NR 27 TC 31 Z9 34 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JAN PY 2006 VL 20 IS 1 BP 72 EP 78 DI 10.1111/j.1365-3016.2006.00696.x PG 7 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 001NL UT WOS:000234543500009 PM 16420344 ER PT J AU Muller, A Sherman, R Weiss, J Addison, R Carr, D Harden, RN AF Muller, Andre Sherman, Richard Weiss, Jocelyn Addison, Robert Carr, Daniel Harden, R. Norman TI Neurophysiology of pain from landmine injury SO PAIN MEDICINE LA English DT Article ID PRIMARY SENSORY NEURONS; ROOT GANGLION NEURONS; SPINAL DORSAL HORN; RAT SCIATIC-NERVE; PHANTOM LIMB PAIN; CORTICAL REORGANIZATION; NEUROPATHIC PAIN; PLASTICITY; CORD; CONSTRICTION C1 Hop Civil, Ctr Etud & Traitement Douleur, Strasbourg, France. Behav Med Res & Training Fdn, Suquamish, WA USA. NCI, Occupat & Epidemiol Branch, NIH, Bethesda, MD 20892 USA. France USA Pain Assoc, Washington, DC USA. Rehabil Inst Chicago, Ctr Pain Studies, Chicago, IL 60611 USA. Tufts Univ New England Med Ctr, Dept Anesthesia, Boston, MA USA. Javelin Pharmaceut Inc, Cambridge, MA USA. RP Muller, A (reprint author), Hop Civil, Ctr Etud & Traitement Douleur, Strasbourg, France. NR 35 TC 1 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2006 VL 7 SU 2 BP S204 EP S208 DI 10.1111/j.1526-4637.2006.00234_5.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 119IO UT WOS:000243006200005 PM 17112353 ER PT J AU Riley, EM Wahl, S Perkins, DJ Schofield, L AF Riley, EM Wahl, S Perkins, DJ Schofield, L TI Regulating immunity to malaria SO PARASITE IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Immunology of Malaria Infections - Implications for the Design and Development of Malaria Vaccines CY FEB 08-11, 2005 CL Johns Hopkins Bloomberg Sch Public Hlth, Baltimore, MD HO Johns Hopkins Bloomberg Sch Public Hlth DE anti-toxic immunity; glycosylphosphatidylinositol; IL-10; nitric oxide; regulatory T cell; TGF-beta ID NITRIC-OXIDE PRODUCTION; PLASMODIUM-FALCIPARUM MALARIA; IMMUNOREGULATORY T-CELLS; NATURAL-KILLER COMPLEX; NECROSIS-FACTOR-ALPHA; SYNTHASE TYPE-2 EXPRESSION; TRANSCRIPTION FACTOR FOXP3; CD1D-RESTRICTED NKT CELLS; SYMPATRIC ETHNIC-GROUPS; BLOOD-STAGE MALARIA AB The optimal outcome of a malaria infection is that parasitized cells are killed and degraded without inducing significant pathology. Since much of the pathology of malaria infection can be immune-mediated, this implies that immune responses have to be carefully regulated. The mechanisms by which antimalarial immune responses are believed to be regulated were discussed at the recent Malaria Immunology Workshop (Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; February 2005). Potential regulatory mechanisms include regulatory T cells, which have been shown to significantly modify cellular immune responses to various protozoan infections, including leishmania and malaria; neutralising antibodies to pro-inflammatory malarial toxins such as glycosylphosphatidylinositol and haemozoin; and self-regulating networks of effector molecules. Innate and adaptive immune responses are further moderated by the broader immunological environment, which is influenced by both the genetic background of the host and by co-infection with other pathogens. A detailed understanding of the interplay between these different immunoregulatory processes may facilitate the rationale design of vaccines and novel therapeutics. C1 Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England. NIDCR, NIH, Bethesda, MD USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. RP Riley, EM (reprint author), Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Keppel St, London WC1E 7HT, England. EM eleanor.riley@lshtm.ac.uk RI Riley, Eleanor/C-8960-2013 OI Riley, Eleanor/0000-0003-3447-3570 FU FIC NIH HHS [D43 TW005884]; NIAID NIH HHS [R01 AI051305] NR 147 TC 107 Z9 111 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD JAN-FEB PY 2006 VL 28 IS 1-2 BP 35 EP 49 DI 10.1111/j.1365-3024.2006.00775.x PG 15 WC Immunology; Parasitology SC Immunology; Parasitology GA 007PS UT WOS:000234982300006 PM 16438675 ER PT S AU Hill, NJ Lal, TN Schroder, M Hinterberger, T Widman, G Elger, CE Schoelkopf, B Birbaumer, N AF Hill, N. Jeremy Lal, Thomas Navin Schroeder, Michael Hinterberger, Thilo Widman, Guido Elger, Christian E. Schoelkopf, Bernhard Birbaumer, Niels BE Franke, K Muller, KR Nickolay, B Schafer, R TI Classifying event-related desynchronization in EEG, ECoG and MEG signals SO PATTERN RECOGNITION, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 28th Annual Symposium of the Gernan-Association-for-Pattern-Recognition CY SEP 12-14, 2006 CL Fraunhofer Inst IPK, Berlin, GERMANY SP German Assoc Pattern Recognit, Fraunhofer Inst HHI, Frauhofer Inst FIRST HO Fraunhofer Inst IPK ID SELECTION AB We employed three different brain signal recording methods to perform Brain-Computer Interface studies on untrained subjects. In all cases, we aim to develop a system that could be used for fast, reliable preliminary screening in clinical BCI application, and we are interested in knowing how long screening sessions need to be. Good performance could be achieved, on average, after the first 200 trials in EEG, 75-100 trials in MEG, or 25-50 trials in ECoG. We compare the performance of Independent Component Analysis and the Common Spatial Pattern algorithm in each of the three sensor types, finding that spatial filtering does not help in MEG, helps a little in ECoG, and improves performance a great deal in EEG. In all cases the unsupervised ICA algorithm performed at least as well as the supervised CSP algorithm, which can suffer from poor generalization performance due to overfitting, particularly in ECoG and MEG. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Fraunhofer FIRST IDA Grp, D-12489 Berlin, Germany. Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Univ Bonn, Dept Epileptol, D-5300 Bonn, Germany. NIH, Human Cort Physiol Unit, Bethesda, MD 20892 USA. RP Hill, NJ (reprint author), Max Planck Inst Biol Cybernet, Spemannstr 38, D-72076 Tubingen, Germany. EM jeremy.hill@tuebingen.mpg.de; navin.lal@tuebingen.mpg.de; michael.schroeder@first.fraunhofer.de; thilo.hinterberger@uni-tuebingen.de; guido.widman@ukb.uni-bonn.de; christian.eiger@ukb.uni-bonn.de; bernhard.schoelkopf@tuebingen.mpg.de; niels.birbaumer@uni-tuebingen.de RI Scholkopf, Bernhard/A-7570-2013 NR 11 TC 14 Z9 14 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44412-2 J9 LECT NOTES COMPUT SC PY 2006 VL 4174 BP 404 EP 413 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BFE65 UT WOS:000241486800041 ER PT J AU Mansky, PJ Koh, JM AF Mansky, PJ Koh, JM TI Botanicals in pediatric leukemia: Potential and pitfalls SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID IN-VITRO; CELL-PROLIFERATION; CROTON-LECHLERI; EXTRACTS; CANCER; COMPLEMENTARY; STIMULATION; GROWTH C1 Natl Ctr Complementary & Alternat Med, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Mansky, PJ (reprint author), Natl Ctr Complementary & Alternat Med, Div Intramural Res, NIH, 10 Ctr Dr Bldg 10,CRC,Room 4-1730,MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov FU Intramural NIH HHS NR 19 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JAN PY 2006 VL 46 IS 1 BP 8 EP 10 DI 10.1002/pbc.20657 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 989OZ UT WOS:000233684800003 PM 16261602 ER PT J AU Chesney, RW Brewer, E Moxey-Mims, M Watkins, S Furth, SL Harmon, WE Fine, RN Portman, RJ Warady, BA Salusky, IB Langman, CB Gipson, D Scheidt, P Feldman, H Kaskel, FJ Siegel, NJ AF Chesney, RW Brewer, E Moxey-Mims, M Watkins, S Furth, SL Harmon, WE Fine, RN Portman, RJ Warady, BA Salusky, IB Langman, CB Gipson, D Scheidt, P Feldman, H Kaskel, FJ Siegel, NJ TI Report of an NIH task force on research priorities in chronic kidney disease in children SO PEDIATRIC NEPHROLOGY LA English DT Editorial Material ID CHRONIC-RENAL-FAILURE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; INTERMITTENT CALCITRIOL THERAPY; PEDIATRIC HEMODIALYSIS-PATIENTS; LEFT-VENTRICULAR HYPERTROPHY; GLYCATION END-PRODUCTS; CASE-COHORT DESIGNS; QUALITY-OF-LIFE; DIALYSIS PATIENTS; PREDIALYSIS PATIENTS AB This is a summary of the Task Force on Chronic Kidney Disease in Children convened April 24, 2002, by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) in Bethesda, MD, USA. The goal of this Task Force was to hear expert advice on the value of systematic collection of information about children who have or who are at risk for kidney disease, and to discern research priorities in this area. A panel of 30 experts discussed open and relevant topics in their areas of expertise. A more complete knowledge is needed concerning the definition, etiology, pathogenesis, natural history, epidemiology and therapeutic strategies for chronic kidney disease in children. C1 Univ Tennessee, Hlth Sci Ctr, Dept Paediat, Memphis, TN 38103 USA. Texas Childrens Hosp, Paediat Renal Serv, Houston, TX 77030 USA. NIDDK, NIH, DKUH, Bethesda, MD 20892 USA. Childrens Hosp & Med Ctr, Div Nephrol, Seattle, WA 98105 USA. Childrens Hosp, Boston, MA 02115 USA. SUNY Stony Brook, Dept Pediat, Childrens Med Ctr, Stony Brook, NY 11794 USA. Univ N Carolina, Div Nephrol & Hypertens, Chapel Hill, NC 27516 USA. Univ Texas, Houston, TX 77030 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. NICHHD, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Montefiore Med Ctr, Dept Pediat, Bronx, NY 10467 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. RP Chesney, RW (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Paediat, 50 N Dunlap, Memphis, TN 38103 USA. EM RChesney@utmem.edu FU NIDDK NIH HHS [U01 DK066174] NR 127 TC 14 Z9 15 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JAN PY 2006 VL 21 IS 1 BP 14 EP 25 DI 10.1007/s00467-005-2087-2 PG 12 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 990JW UT WOS:000233740100004 PM 16252095 ER PT J AU Cunnane, SC Ryan, MA Lin, YH Lim, SY Salem, N AF Cunnane, SC Ryan, MA Lin, YH Lim, SY Salem, N TI Suckling rats actively recycle carbon from a-linolenate into newly synthesized lipids even during extreme dietary deficiency of n-3 polyunsaturates SO PEDIATRIC RESEARCH LA English DT Article ID SPATIAL TASK-PERFORMANCE; DOCOSAHEXAENOIC ACID; FATTY-ACIDS; DEVELOPING BRAIN; DE-NOVO; METABOLISM; LIVER; RADIOACTIVITY; LINOLEATE; WOMEN AB Docosahexaenoate is usually considered to be the principal endpoint of alpha-linolenate metabolism in mammals. Nevertheless, several studies over the past 30 y have shown that more carbon from cc-linolenate is recycled into newly synthesized lipids than is used to make docosahexacnoate. Our objective in this study was to assess carbon recycling from a-linolenate in suckling rats made deficient in n-3 polyunsaturated fatty acids (PUFA). Female Long-Evans rats were given a diet deficient in n-3 PUFA at weaning and then bred 8 wk later. Pups from the second generation were nursed by their respective dams and gavaged with 1 mg [U-C-13]-alpha- linolenate at 10 d old. Brain and liver were obtained 24 h later, and the fatty acid profiles and C-13 enrichment analyzed. Docosahexaenoate was markedly depleted in brain (-82%) and liver (-97%) of the n-3 PUFA-deficient rats. In the controls, C-13 enrichment in products of carbon recycling (cholesterol and fatty acids other than n-3 PUFA) exceeded that in docosahexaenoate by 2.4-fold (liver) and 7.5-fold (brain). n-3 PUFA deficiency reduced the ratio of C-13 enrichment in products of carbon recycling compared with C-13 incorporated into docosahexaenoate by 63% in the brain but not in the liver. Despite severe n-3 PUFA deficiency, carbon recycling still consumed 50% more C-13 from a-linolenate than went into docosahexaenoate in the liver and 2.8-fold more in the brain. We conclude that carbon recycling is an integral part of neonatal metabolism of a-linolenate and is not simply an overflow pathway arising front excess availability of preformed docosahexaenoate. C1 Univ Sherbrooke, Geriatr Inst, Res Ctr Aging, Sherbrooke, PQ J1H 4C4, Canada. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD USA. Korea Maritime Univ, Div Oecan Sci, Pusan 606791, South Korea. RP Cunnane, SC (reprint author), Univ Sherbrooke, Geriatr Inst, Res Ctr Aging, 1036 Belvedere S, Sherbrooke, PQ J1H 4C4, Canada. EM stephen.cunnane@usherbrooke.ca FU Intramural NIH HHS NR 20 TC 13 Z9 13 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2006 VL 59 IS 1 BP 107 EP 110 DI 10.1203/01.pdr.0000190569.07991.ed PG 4 WC Pediatrics SC Pediatrics GA 997UY UT WOS:000234275500021 PM 16326997 ER PT J AU Cotton, RB Sundell, HW Zeldin, DC Morrow, JD Roberts, LJ Hazinski, TA Law, AB Steele, S AF Cotton, RB Sundell, HW Zeldin, DC Morrow, JD Roberts, LJ Hazinski, TA Law, AB Steele, S TI Inhaled nitric oxide attenuates hyperoxic lung injury in lambs SO PEDIATRIC RESEARCH LA English DT Article ID GAS-EXCHANGE; LIPID-PEROXIDATION; OXIDATIVE STRESS; OXYGEN-TENSION; INHIBITION; INCREASES; INFANTS; CYTOCHROME-P-450; 8-ISOPROSTANE; ACCUMULATION AB Cytochrome P450 (CYP) inhibition with cimetidine reduces hyperoxic lung injury in young lambs. Nitric oxide (NO), also a CYP inhibitor, has been shown to either aggravate or protect against oxidant stress depending on experimental context. The objective of this study was to determine whether NO, like cimetidine, would protect young lambs against hyperoxic lung injury, and whether its effect was associated with CYP inhibition. Three groups of lambs were studied: 1) room air exposure, 2) > 95% O-2, and 3) > 95% O-2 plus inhaled NO. After 72 h, hyperoxia alone resulted in a significant increase in arterial PCO2 and number of polymorphonuclear leukocytes in bronchoalveolar lavage (BAL), and a significant decrease in arterial/alveolar O-2 tension (a/A). The addition of inhaled NO significantly decreased the hypercarbia and BAL polymorphonuclear cellular response associated with hyperoxia but had no beneficial effect on a/A ratio. There were no significant differences in F-2-isoprostanes or isofurans (markers of lipid peroxidation) measured in BAL or lung tissue among study groups. No intergroup differences were detected in BAL epoxyeicosatrienoic acid levels (index of CYP activity). The results of this study indicate that hypercarbia and inflammation accompanying hyperoxic lung injury in young lambs can be attenuated by inhaled NO. However, this study provides no direct evidence that NO is inhibiting CYP-mediated oxidant lung injury. C1 Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Cotton, RB (reprint author), Vanderbilt Childrens Hosp, Room 11112 Doctors Off Tower,2200 Childrens Way, Nashville, TN 37232 USA. EM robert.cotton@vanderbilt.edu FU Intramural NIH HHS; NHLBI NIH HHS [HL56697]; NIDDK NIH HHS [DK26657]; NIGMS NIH HHS [GM15431, GM42056] NR 30 TC 19 Z9 20 U1 0 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2006 VL 59 IS 1 BP 142 EP 146 DI 10.1203/pdr.0000191815.60293.cc PG 5 WC Pediatrics SC Pediatrics GA 997UY UT WOS:000234275500028 PM 16327001 ER PT J AU Benjamin, DK Stoll, BJ Fanaroff, AA McDonald, SA Oh, W Higgins, RD Duara, S Poole, K Laptook, A Goldberg, R AF Benjamin, DK Stoll, BJ Fanaroff, AA McDonald, SA Oh, W Higgins, RD Duara, S Poole, K Laptook, A Goldberg, R CA Natl Inst Child Hlth Human Dev Neo TI Neonatal candidiasis among extremely low birth weight infants: Risk factors, mortality rates, and neurodevelopmental outcomes at 18 to 22 months SO PEDIATRICS LA English DT Article DE candidiasis; meningitis; sensitivity; specificity; culture; premature infant ID INFECTION; COLONIZATION; FLUCONAZOLE; PROPHYLAXIS; MENINGITIS; CANDIDEMIA; NETWORK; SEPSIS AB BACKGROUND. Neonatal candidiasis is associated with substantial morbidity and mortality rates. Neurodevelopmental follow-up data for a large multicenter cohort have not been reported. METHODS. Data were collected prospectively for neonates born at < 1000 g at National Institute of Child Health and Human Development-sponsored Neonatal Research Network sites between September 1, 1998, and December 31, 2001. Uniform follow-up evaluations, including assessments of mental and motor development with the Bayley Scales of Infant Development II, were completed for all survivors at corrected ages of 18 to 22 months. We evaluated risk factors for the development of neonatal candidiasis, responses to antifungal therapy, and the association between candidiasis and subsequent morbidity and death. RESULTS. The cohort consisted of 4579 infants; 320 of 4579 (7%) developed candidiasis; 307 of 320 had Candida isolated from blood, 27 of 320 had Candida isolated from cerebrospinal fluid, and 13 (48%) of 27 of those with meningitis had negative blood cultures. In multivariate analysis of risk factors on day of life 3, birth weight, cephalosporins, gender, and lack of enteral feeding were associated with development of candidiasis. After diagnosis, most neonates had multiple positive cultures despite antifungal therapy, and 10% of neonates had candidemia for >= 14 days. Death or neurodevelopmental impairment (NDI) was observed for 73% of extremely low birth weight infants who developed candidiasis. Death and NDI rates were greater for infants who had delayed removal or replacement of central catheters (>= 1 day after initiation of antifungal therapy), compared with infants whose catheters were removed or replaced promptly. CONCLUSIONS. Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates. C1 Duke Univ, Duke Clin Res Inst, Dept Pediat, Durham, NC 27705 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. NICHHD, Bethesda, MD 20892 USA. Univ Miami, Jackson Mem Hosp, Miami, FL 33136 USA. RP Benjamin, DK (reprint author), Duke Univ, Duke Clin Res Inst, Dept Pediat, POB 17969, Durham, NC 27705 USA. EM danny.benjamin@duke.edu FU NCRR NIH HHS [M01 RR 00070, M01 RR 00039, M01 RR 00044, M01 RR 00750, M01 RR 00997, M01 RR 01032, M01 RR 02172, M01 RR 02635, M01 RR 06022, M01 RR 08084]; NICHD NIH HHS [HD044799-01, U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27904, U10 HD34167, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40689] NR 17 TC 278 Z9 301 U1 0 U2 11 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2006 VL 117 IS 1 BP 84 EP 92 DI 10.1542/peds.2004-2292 PG 9 WC Pediatrics SC Pediatrics GA 999QV UT WOS:000234406100012 PM 16396864 ER PT J AU Wurtz, RH Sommer, MA AF Wurtz, R. H. Sommer, M. A. TI A corollary discharge for perceptual stability SO PERCEPTION LA English DT Meeting Abstract C1 NIH, NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Neurosci & Ctr Neural Basis Cognit, Pittsburgh, PA 15260 USA. EM bob@lsr.nei.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2006 VL 35 SU S BP 10 EP 11 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 127PR UT WOS:000243599300032 ER PT J AU Bondar, IV Leopold, D Logothetis, NK AF Bondar, I. V. Leopold, D. Logothetis, N. K. TI Pattern-selective cortical neurons show long-term stability in their stimulus preferences and temporal dynamics SO PERCEPTION LA English DT Meeting Abstract C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Russian Acad Sci, Inst High Nervous Activ & Neurophysiol, Moscow 117485, Russia. Natl Inst Hlth, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. EM bondar@ihna.ru NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2006 VL 35 SU S BP 121 EP 121 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 127PR UT WOS:000243599300383 ER PT J AU Golenhofen, N Redel, A Wawrousek, EF Drenckhahn, D AF Golenhofen, N Redel, A Wawrousek, EF Drenckhahn, D TI Ischemia-induced increase of stiffness of alpha B-crystallin/HSPB2-deficient myocardium SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE alpha B-crystallin; HSPB2; stress proteins; titin; ischemia; contractility; mouse papillary muscle; diastolic relaxation ID ALPHA-B-CRYSTALLIN; HEAT-SHOCK-PROTEIN; DILATED CARDIOMYOPATHY; CARDIAC TITIN; RAT HEARTS; MUSCLE; REPERFUSION; ASSOCIATION; MUTATIONS; CHAPERONE AB The two small heat shock proteins (sHSPs), alpha B-crystallin and HSPB2, have been shown to translocate within a few minutes of cardiac ischemia from the cytosol to myofibrils; and it has been suggested that their chaperone-like properties might protect myofibrillar proteins from unfolding or aggregation during stress conditions. Further evidence of an important role for HSPs in muscle function is provided by the fact that mutations of the alpha B-crystallin gene cause myopathy and cardiomyopathy. In the present study, we subjected isolated papillary muscles of alpha B-crystallin/HSPB2-deficient mice to simulated ischemia and reperfusion. During ischemia in alpha B-crystallin/HSPB2-deficient muscles, the development of contracture started earlier and reached a higher value compared to the wildtype mice. The recovery of contracture of alpha B-crystallin/HSPB2-deficient muscles was also attenuated during the simulated reperfusion period. However, twitch force was not significantly altered at any time of the experiment. This suggests that during ischemic insults, alpha B-crystallin/HSPB2 may not be important for the contraction process itself, but rather serve to maintain muscular elasticity. C1 Univ Wurzburg, Inst Anat & Cell Biol, D-97070 Wurzburg, Germany. NEI, NIH, Bethesda, MD 20892 USA. RP Golenhofen, N (reprint author), Univ Wurzburg, Inst Anat & Cell Biol, Koellikerstr 6, D-97070 Wurzburg, Germany. EM nikola.golenhofen@medizin.uni-ulm.de RI Wawrousek, Eric/A-4547-2008 NR 36 TC 28 Z9 29 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 2006 VL 451 IS 4 BP 518 EP 525 DI 10.1007/s00424-005-1488-1 PG 8 WC Physiology SC Physiology GA 993FD UT WOS:000233939100003 PM 16217658 ER PT J AU Land, S AF Land, S TI Quality-of-life valuations of advanced breast cancer by New Zealand women SO PHARMACOECONOMICS LA English DT Letter ID COST-EFFECTIVENESS; HEALTH; RECOMMENDATIONS; MEDICINE C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NSABP, Pittsburgh, PA USA. RP Land, S (reprint author), NSABP, Pittsburgh, PA USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2006 VL 24 IS 4 BP 415 EP 416 DI 10.2165/00019053-200624040-00010 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 038OU UT WOS:000237233000010 PM 16605286 ER PT J AU Furuno, JP Metlay, JP Harnett, JP Wilson, J Langenberg, P McGregor, JC Zhu, JK Perencevich, EN AF Furuno, JP Metlay, JP Harnett, JP Wilson, J Langenberg, P McGregor, JC Zhu, JK Perencevich, EN TI Population antibiotic susceptibility for Streptococcus pneumoniae and treatment outcomes in common respiratory tract infections SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE Streptococcus pneumoniae; ecological analysis; respiratory tract infection; antibiotic resistance; outcomes ID ACUTE OTITIS-MEDIA; BACTEREMIC PNEUMOCOCCAL PNEUMONIA; ANTIMICROBIAL RESISTANCE; UNITED-STATES; MANAGED CARE; CLINICAL OUTCOMES; ACUTE SINUSITIS; IMPACT; TRENDS; EXACERBATIONS AB Purpose Antibiotic-resistant Streptococcus pneumoniae potentially threatens the successful treatment of common respiratory tract infections (RTls); however, the relationship between antibiotic resistance and treatment outcomes remains unclear. We aimed to test the hypothesis that higher in vitro penicillin and erythromycin nonsusceptibility levels among clinical isolates of S. pneumoniae are associated with higher risk of treatment failure in suppurative acute otitis media (AOM), acute sinusitis, and acute exacerbation of chronic bronchitis (AECB). Methods We conducted a population-level analysis using treatment outcomes data from a national, managed-care claims database, and antibiotic susceptibility data from a national repository of antimicrobial susceptibility results between 1997 and 2000. Treatment outcomes in patients with suppurative AOM, acute sinusitis, or AECB receiving selected macrolides or beta-lactams were assessed. Associations between RTI-specific treatment outcomes and antibiotic nonsusceptibility were determined using Spearman correlation coefficients with condition-specific paired outcome and susceptibility data for each region and each year. Results There were 649 552 available RTI outcomes and 7252 susceptibility tests performed on S. pneumoniae isolates. There were no statistically significant trends across time for resolution proportions following treatment by either beta-lactams or macrolides among any of the RTIs. Correlation analyses found no statistically significant association between S. pneumoniae susceptibility and RTI treatment outcomes apart from a significant positive association between of erythromycin nonsusceptibility in ear isolates and macrolide treatment resolution for suppurative AOM. Conclusion On the population level, in vitro S. pneumoniae nonsusceptibility to macrolide or beta-lactam antibiotics was not associated with treatment failure in conditions of probable S. pneumoniae etiology. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Pfizer Inc, US Outcomes Res Grp, New York, NY USA. NIH, Natl Ctr Minor Hlth & Hlth Disparities, Bethesda, MD 20892 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. VA Maryland Healthcare Syst, Baltimore, MD USA. RP Furuno, JP (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 100 N Greene St,Lower Level, Baltimore, MD 21201 USA. RI McGregor, Jessina/A-7625-2008 NR 39 TC 6 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2006 VL 15 IS 1 BP 1 EP 9 DI 10.1002/pds.1135 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 006CO UT WOS:000234872900001 PM 16136615 ER PT J AU Vasiliou, V Ziegler, TL Bludeau, P Petersen, DR Gonzalez, FJ Deitrich, RA AF Vasiliou, V Ziegler, TL Bludeau, P Petersen, DR Gonzalez, FJ Deitrich, RA TI CYP2E1 and catalase influence ethanol sensitivity in the central nervous system SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE ethanol metabolism; CYP2E1; catalase; brain; liver ID HEPATIC-MICROSOMAL ETHANOL; INDUCED LOCOMOTOR-ACTIVITY; BRAIN CATALASE; OXIDIZING SYSTEM; RAT-BRAIN; CYTOCHROME P-4502E1; INBRED STRAINS; MICE; ACETALDEHYDE; METABOLISM AB Objectives Genetic factors are known to influence the sensitivity and tolerance to ethanol in humans and laboratory animals. Ethanol is metabolized to acetaldehyde mainly by the alcohol dehydrogenase pathway (ADHs) and, to a lesser extent, by microsomal oxidization (CYP2E1) and the catalase-H2O2 system. Methods In this study, we examined the role of CYP2E1 and catalase in ethanol metabolism and sensitivity, using transgenic knockout Cyp2e1(-/-) mice, acatalasemic (CSb/CSb) mice, double mutant Cyp2e1 (-/-)/CSb/CSb mice and their respective wild-type counterparts 129/sv, C3H/HeJ, 1291sv X C3H/HeJ mice. Ethanol was administered to the mouse lines and ethanol pharmacokinetics and sleep times were evaluated. Results Although the rates of whole blood ethanol elimination following i.p. administration were found to be similar regardless of dose or genetic stock, CSb/CSb, Cyp2e1(-/-) and Cyp2el (-/-)/CSb/CSb mice exhibited longer ethanol-induced sleep times, especially at higher ethanol doses. This infers that there is less acetaldehyde produced in the brains of these animals and is in opposition to the idea that increased acetaldehyde increases the actions of ethanol. The Cyp2el((-)/(-)) animals produced lower whole blood levels of acetaldehyde than wild-type controls; however, this difference was seen only at higher doses of ethanol. The amount of acetaldehyde produced following the incubation of ethanol with liver and brain microsomes was greater in tissues derived from 129/sv than in those from Cyp2e1(-/-) mice. Conclusions Although the contribution of CYP2E1 and catalase in ethanol oxidation may be of little significance, these enzymes appear to play a significant role in ethanol sensitivity in the brain. Pharmacogenetics and Genomics 16:51-58. (c) 2006 Lippincott Williams & Wilkins. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Pharmacol, Denver, CO 80262 USA. Natl Canc Inst, Natl Inst Hlth, Bethesda, MD USA. RP Vasiliou, V (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, 4200 E 9th Ave, Denver, CO 80262 USA. EM vasilis.vasiliou@uchsc.edu FU NIAAA NIH HHS [5T32AA07464, P50-AA03527, R01 AA11885, R21-AA12284]; PHS HHS [KO5-0093] NR 46 TC 25 Z9 25 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2006 VL 16 IS 1 BP 51 EP 58 DI 10.1097/01.fpc.0000182777.95555.56 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 997VR UT WOS:000234277400007 PM 16344722 ER PT J AU Davies, MA Setola, V Strachan, RT Sheffler, DJ Salay, E Hufeisen, SJ Roth, BL AF Davies, MA Setola, V Strachan, RT Sheffler, DJ Salay, E Hufeisen, SJ Roth, BL TI Pharmacologic analysis of non-synonymous coding h5-HT2A SNPs reveals alterations in atypical antipsychotic and agonist efficacies SO PHARMACOGENOMICS JOURNAL LA English DT Article DE 5-HT2A; serotonin receptors; T25N; I197V; A447V; H452Y ID 5-HT2A RECEPTOR GENE; SEROTONIN RECEPTORS; ROBUST PHARMACOLOGY; CLOZAPINE RESPONSE; CLINICAL-RESPONSE; SCHIZOPHRENIA; ARIPIPRAZOLE; PHARMACOGENETICS; DRUG; ASSOCIATION AB The 5-HT2A-serotonin receptor is a major molecular target for most atypical antipsychotic drugs as well as most hallucinogens, which can exacerbate psychotic symptoms. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT2A-serotonin receptor could explain inter-individual variability in atypical antipsychotic and agonist drug response. We examined the in vitro pharmacology of four non-synonymous SNPs, which give rise to T25N, I197V, A447V, and H452Y variant 5-HT2A-serotonin receptors. Our data indicate that these non-synonymous SNPs exert statistically significant, although modest, effects on the affinity and functional effects of several currently approved atypical antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone). Also, the 5-HT2A receptor SNPs slightly altered the potency and relative efficacy of a small number of selected agonists (2,5-dimethoxy-4-iodoamphetamine, tryptamine, 5-hydroxytryptamine, m-chlorophenylpiperazine, and 5-methoxy-N, N-dimethyltryptamine). In all, our results show that the in vitro pharmacological effects of the SNPs are drug specific. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, RM W411,2109 Adelbert Rd, Cleveland, OH 44106 USA. EM bryan.roth@case.edu RI Roth, Bryan/F-3928-2010 FU NIMH NIH HHS [K02MH01366, R01MH57635] NR 51 TC 31 Z9 34 U1 3 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JAN-FEB PY 2006 VL 6 IS 1 BP 42 EP 51 DI 10.1038/sj.tpj.6500342 PG 10 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 033XU UT WOS:000236889100008 PM 16314884 ER PT J AU Beyl, S Hohaus, A Stary, A Kudrnac, M Guy, RH Timin, EN Hering, S AF Beyl, S. Hohaus, A. Stary, A. Kudrnac, M. Guy, R. H. Timin, E. N. Hering, S. TI Evidence for trapping of a charged phenylalkylamine in Ca(V)1.2 SO PHARMACOLOGY LA English DT Meeting Abstract CT 12th Symposium of the Austrian-Pharmacological-Society CY NOV 23-25, 2006 CL Vienna, AUSTRIA SP Austrian Pharmacol Soc C1 Univ Vienna, Inst Pharmacol & Toxicol, Vienna, Austria. Univ Vienna, Inst Theoret Chem, Vienna, Austria. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PY 2006 VL 78 IS 3 BP 145 EP 145 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 099PY UT WOS:000241609000010 ER PT J AU Fantegrossi, WE Harrington, AW Kiessel, CL Eckler, JR Rabin, RA Winter, JC Coop, A Rice, KC Woods, JH AF Fantegrossi, WE Harrington, AW Kiessel, CL Eckler, JR Rabin, RA Winter, JC Coop, A Rice, KC Woods, JH TI Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE hallucinogens; drug-discrimination; head twitch response; serotonin receptors ID LYSERGIC-ACID DIETHYLAMIDE; HEAD-TWITCH RESPONSE; 5-HT2C RECEPTORS; DISCRIMINATIVE STIMULUS; LSD; 5-HYDROXYTRYPTAMINE; ANTAGONISTS; SEROTONIN; DRUGS; INDOLEALKYLAMINES AB Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)(2A) antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT2A and 5-HT2C receptors, but much higher affinity for 5-HT1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M 100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT1A receptor. (C) 2006 Elsevier Inc. All rights reserved. C1 Emory Univ, Yerkes Natl Primate Res Ctr, Div Neurosci, Atlanta, GA 30322 USA. Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14260 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Fantegrossi, WE (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Div Neurosci, 954 Gatewood Rd, Atlanta, GA 30322 USA. EM wfanteg@emory.edu FU NIDA NIH HHS [K02 DA019634, K02 DA019634-01, DA 03385, DA05923, DA09161] NR 46 TC 44 Z9 44 U1 4 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 2006 VL 83 IS 1 BP 122 EP 129 DI 10.1016/j.pbb.2005.12.015 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 028FM UT WOS:000236472300014 PM 16460788 ER PT J AU Soderblom, C Blackstone, C AF Soderblom, C Blackstone, C TI Traffic accidents: Molecular genetic insights into the pathogenesis of the hereditary spastic paraplegias SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE mitochondria; transport; axon; degeneration; golgi apparatus; vesicle trafficking; myelin; endocytosis; motor; chaperone ID NUCLEOTIDE EXCHANGE FACTOR; HEAVY-CHAIN KIF5A; PELIZAEUS-MERZBACHER-DISEASE; PROTEOLIPID PROTEIN GENE; FAST AXONAL-TRANSPORT; MOTOR-NEURON-DISEASE; MAMMALIAN-CELLS; TROYER-SYNDROME; MICE LACKING; CNS MYELIN AB The hereditary spastic paraplegias (HSPs) comprise a clinically and genetically diverse group of inherited neurological disorders in which the primary manifestation is progressive spasticity and weakness of the lower limbs. The identification of over 25 genetic loci and 11 gene products for these disorders has yielded new insights into the molecular pathways involved in the pathogenesis of HSPs. In particular, causative mutations in proteins implicated in mitochondrial function, intracellular transport and trafficking, axonal development, and myelination have been identified. In many cases, the proper intracellular trafficking and distribution of molecules and organelles are ultimately thought to be involved in HSP pathogenesis. In fact, deficits in intracellular cargo trafficking and transport are concordant with the length dependence of the distal axonopathy of upper motor neurons observed in HSP patients. Through a better understanding of the functions of the HSP gene products, novel therapeutic targets for treatment and prevention are being identified. Published by Elsevier Inc. C1 NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, NIH, Bldg 35,Room 2C-913,Convent Dr, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov NR 122 TC 54 Z9 56 U1 1 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 2006 VL 109 IS 1-2 BP 42 EP 56 DI 10.1016/j.pharmthera.2005.06.001 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 996GK UT WOS:000234162200004 PM 16005518 ER PT S AU Kasperlik-Zaluska, AA Roslonowska, E Slowinska-Srzednicka, J Otto, M Cichocki, A Cwikla, J Slapa, R Eisenhofer, G AF Kasperlik-Zaluska, Anna A. Roslonowska, Elzbieta Slowinska-Srzednicka, Jadwiga Otto, Maciej Cichocki, Andrzej Cwikla, Jaroslaw Slapa, Rafal Eisenhofer, Graeme BE Pacak, K Eisenhofer, G TI 1,111 Patients with adrenal incidentalomas observed at a single endocrinological center - Incidence of chromaffin tumors SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE adrenal incidentaloma; pheochromocytoma; paraganglioma; chromaffin tumors; metanephrines; hypertension ID PHEOCHROMOCYTOMA; DIAGNOSIS; METANEPHRINES AB A majority of incidentally found adrenal tumors derive from the adrenal cortex. The aim of our study was evaluation of the incidence of chromaffin tumors in a group of 1,111 patients with adrenal inciden-talomas. In this group there were 803 women and 308 men, aged 1087 years. Clinical examination, imaging studies (ultrasound scans, CT, and MRI if necessary), and hormonal determinations (cortisol, ACTH and androgens in the blood, dexamethasone suppression test, urinary excretion of 17-OHCS, aldosterone and 17-KS, as well as PRA/aldosterone stimulation test and metanephrines in hypertensive patients and those with density in CT over 20 HU) were used. In 380 patients treated by surgery (mainly by laparoscopic approach), histological and immunocytochemical examinations were performed. Clinical examination revealed hypertension in 25% of the patients under study. Chromaffin tumors were detected in 43 patients, 33 women, and 10 men aged 20-75 years: pheochromocytoma in 36 (malignant in 3); chromaffin cells hyperplasia in 2; paraganglioma in 3; ganglioneuroblastoma in 1; ganglioneuroma in 1; and schwannoma in 2. The tumors' diameter ranged between 1.1 and 20.0 cm, density = 25 Hounsfield units (HU) or more before contrast medium injection. Hypertension was present in 53% of these patients. The urinary metanephrines excretion was elevated in 31 of 38 patients, in whom the determinations were done. Chromaffin tumors were detected in 4% (pheochromocytomas in 3%) of 1,111 patients with adrenal incidentalomas. Malignancy was present in 9% of 43 patients with chromaffin tumors. High density in CT was a very important diagnostic finding in the incidentally found medullary tumors. C1 Ctr Postgrad Med Educ, Dept Endocrinol, Warsaw, Poland. Warsaw Univ Med, Dept Vasc Surg, Warsaw, Poland. Inst Oncol, Dept Surg, Warsaw, Poland. MSW&A Hosp, Dept Imaging, Warsaw, Poland. Warsaw Univ Med, Dept Imaging, Warsaw, Poland. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD USA. RP Kasperlik-Zaluska, AA (reprint author), Med Ctr Postgrad Educ, Ceglowska 80, PL-01809 Warsaw, Poland. EM anna@ultima.neostrada.pl NR 13 TC 31 Z9 34 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 38 EP 46 DI 10.1196/annals.1353.004 PG 9 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400004 PM 17102070 ER PT S AU Zelinka, T Pacak, K Widimsky, J AF Zelinka, Tomas Pacak, Karel Widimsky, Jiri, Jr. BE Pacak, K Eisenhofer, G TI Characteristics of blood pressure in pheochromocytoma SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; blood pressure; circadian blood pressure rhythm; blood pressure variability ID BETA-ADRENERGIC RECEPTORS; HEART-RATE-VARIABILITY; ORTHOSTATIC HYPOTENSION; SECONDARY HYPERTENSION; CATECHOLAMINES; TACHYCARDIA; REMOVAL; VOLUME; RHYTHM AB Pheochromocytomas are catecholamine-producing tumors arising from chromaffin cells. One of the most typical symptoms of the catecholamine-excess state is hypertension either in the sustained or paroxysmal form, and its severity does not depend on the level of circulating catecholamines. On the other hand, hypertension in pheochromocytoma is very often characterized by the amelioration or even inversion of the circadian blood pressure rhythm. In some subjects, high circulating levels of catecholamines lead to the enhanced blood pressure variability. One possible explanation for such blood pressure variability is the desensitization of the catecholamine receptors due to high levels of circulating catecholamines. C1 Gen Fac Hosp, Dept Med 3, Ctr Hypertens, CZ-12808 Prague 2, Czech Republic. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Zelinka, T (reprint author), Gen Fac Hosp, Dept Med 3, Ctr Hypertens, U Nemocnice 1, CZ-12808 Prague 2, Czech Republic. EM tzeli@lf1.cuni.cz RI Zelinka, Tomas/D-4276-2017 OI Zelinka, Tomas/0000-0003-3395-8373 NR 36 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 86 EP 93 DI 10.1196/annals.1353.009 PG 8 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400009 PM 17102075 ER PT S AU Huynh, TT Pacak, K Wong, DL Linehan, WM Goldstein, DS Elkahloun, AG Munson, PJ Eisenhofer, G AF Huynh, Thanh-Truc Pacak, Karel Wong, Dona L. Linehan, W. Marston Goldstein, David S. Elkahloun, Abdel G. Munson, Peter J. Eisenhofer, Graeme BE Pacak, K Eisenhofer, G TI Transcriptional regulation of phenylethanolamine N-methyltransferase in pheochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; transcription factors; phenylethanolamine; N-methyltransferase; catecholamines; microarray ID CHROMAFFIN CELLS; GENE-EXPRESSION; MESSENGER-RNA; ACTIVATION; PLASMA; EGR-1; METANEPHRINES; HYDROXYLASE; ADRENALINE; PHENOTYPES AB Pheochromocytomas in multiple endocrine neoplasia type 2 (MEN-2) express phenylethanolamine N-methyltransferase (PNMT), the enzyme that catalyzes conversion of norepinephrine to epinephrine, whereas those in von Hippel-Lindau (VHL) syndrome do not. Consequently, pheochromocytomas in MEN-2 produce epinephrine, whereas those in VHL syndrome produce mainly norepinephrine. This study examined whether transcription factors known to regulate expression of PNMT explain the different tumor phenotypes in these syndromes. Quantitative polymerase chain reaction (PCR) and Western blotting were used to assess levels of mRNA and protein for the glucocorticoid receptor, early growth response 1 (Egr-1), the Sp1 transcription factor (Sp1), and MYC-associated zinc finger protein (MAZ) in 6 MEN-2 and 13 VHL tumors. Results were cross-checked with data obtained using microarray gene expression profiling in a further set of 10 MEN-2 and 12 VHL tumors. Pheochromocytomas in MEN-2 and VHL syndrome did not differ in expression of the glucocorticoid receptor, Egr-1, Sp1, or MAZ as assessed by quantitative PCR and Western blotting. Microarray data also indicated no relevant differences in expression of the glucocorticoid receptor, Egr-1, MAZ, and the AP2 transcription factor. Thus, our results do not support a role for the above transcription factors in determining differences in expression of PNMT in pheocbromocytomas from patients with VHL syndrome and MEN-2. Microarray analysis, however, did indicate differences in expression of genes involved in neural crest cell lineage and chromaffin cell development, consistent with differential survival of PNMT-expressing cells in the two syndromes. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. McLean Hosp, Lab Mol & Dev Neurobiol, Belmont, MA 02478 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Ctr Informat Technol, Math & Stat Comp Lab, NIH, Bethesda, MD 20892 USA. RP Eisenhofer, G (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov; ge@box-g.nih.gov FU Intramural NIH HHS NR 28 TC 15 Z9 15 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 241 EP 252 DI 10.1196/annals.1353.026 PG 12 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400026 PM 17102092 ER PT S AU Cleary, S Phillips, JK AF Cleary, Susannah Phillips, Jacqueline K. BE Pacak, K Eisenhofer, G TI The norepinephrine transporter and pheochromocytoma SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE norepinephrine transporter; PC12 cells; uptake assay; cisplatin ID ENDOCRINE NEOPLASIA TYPE-2; RAT ADRENAL-MEDULLA; HIPPEL-LINDAU-SYNDROME; I-131 METAIODOBENZYLGUANIDINE; NORADRENALINE TRANSPORTER; MALIGNANT PHEOCHROMOCYTOMA; PC12 CELLS; NEUROBLASTOMA; LOCALIZATION; EXPRESSION AB Pheochromocytomas are rare neuroendocrine tumors of chromaffin cell origin that synthesize and secrete excess quantities of catecholamines and other vasoactive peptides. Pheochromocytomas also express the norepinephrine transporter (NET), a molecule that is used clinically as a means of incorporating radiolabelled substrates such as I-131-MIBG (iodo-metaiodobenzylguanidine) into pheochromocytoma tumor cells. This allows the diagnostic localization of these tumors and, more recently, I-131-MIBG has been used in trials in the treatment of pheochromocytoma, potentially giving rise to NET As a therapeutic target. However, because of varying levels or activities of the transporter, the ability of I-131-MIBG to be consistently incorporated into tumor cells is limited, and therefore various strategies to increase NET functional activity are being investigated, including the use of traditional chemotherapeutic agents such as cisplatin or doxorubicin. Other aspects of NET discussed in this short review include the regulation of the transporter and how novel protein-protein interactions between NET and structures such as syntaxin 1A may hold the key to innovative ways to increase the therapeutic value of I-131-MIBG. C1 Murdoch Univ, Div Hlth Sci, Murdoch, WA 6150, Australia. NINDS, NIH, Bethesda, MD 20892 USA. RP Phillips, JK (reprint author), Murdoch Univ, Div Hlth Sci, South St, Murdoch, WA 6150, Australia. EM j.k.phillips@murdoch.edu.au RI Phillips, Jacqueline/G-7901-2011 OI Phillips, Jacqueline/0000-0002-4917-7734 NR 32 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 263 EP 269 DI 10.1196/annals.1353.029 PG 7 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400028 PM 17102094 ER PT S AU Elkahloun, AG Powers, JF Nyska, A Etsenhofer, G Tischler, AS AF Elkahloun, Abdel G. Powers, James F. Nyska, Abraham Etsenhofer, Graeme Tischler, Arthur S. BE Pacak, K Eisenhofer, G TI Gene expression profiling of rat pheochromocytoma SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; phenylethanolamine N-methyltransferase; ret proto-oncogene; microarray; heat-shock proteins ID CELL-LINES; PROTEIN; ACTIVATION AB Sporadic and syndrome-associated human pheochromocytomas exhibit a spectrum of common and distinctive phenotypic markers. Animal models may contribute to understanding of common denominators leading to development and progression of pheochromocytoma, and to mechanisms that underlie distinctive phenotypes. Rat pheochromocytomas are common, in contrast to their human counterparts, and their frequency is increased by a variety of genotoxic or nongenotoxic agents. Toxicological studies of rats are therefore a potentially rich source of information on pheochromocytoma biology. To compare the molecular profiles of rat and human pheochromocytomas and to identify pathways potentially involved in pathogenesis of rat pheochromocytomas, we conducted a gene expression profiling study comparing 31 pheochromocytomas obtained from the National Toxicology Program to normal adult rat adrenal medulla. The microarray chips were generated from 31,769-oligomer set representing over 27,200 unique Mouse Ensembl genes. The analysis showed over 1,900 genes that were up- or downregulated in the tumors. More than half of the former are involved in protein synthesis and signal transduction, including oncogenes of the RAS family and several heat shock proteins and chaperones. Downregulated genes included receptors and tumor-suppressor genes, including NF2 and Dmbt1. Specific genes related to neuroendocrine function were either upregulated or downregulated in subsets of tumors. Cross-comparison with a human pheochromocytoma database showed greater than 60% correlation. Results of this study reveal both generic and specific parallels between rat and human pheochromocytomas. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Tufts Univ, New England Med Ctr, Dept Pathol, Boston, MA 02111 USA. Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Elkahloun, AG (reprint author), NHGRI, Genome Technol Branch, NIH, Bldg 50,50 South Dr, Bethesda, MD 20892 USA. EM abdel@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA48017] NR 15 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 290 EP 299 DI 10.1196/annals.1353.033 PG 10 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400032 PM 17102098 ER PT S AU Ohta, S Lai, EW Taniguchi, S Tischler, AS Alesci, S Pacak, K AF Ohta, Shoichiro Lai, Edwln W. Taniguchi, Shun'ichiro Tischler, Arthur S. Alesci, Salvatore Pacak, Karel BE Pacak, K Eisenhofer, G TI Animal models of pheochromocytoma including NIH initial experience SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; animal model; 17-dimethylamino-17-demethoxygeldanamycin (17-DMAG) ID MICE; ACTIVATION; MOUSE; CELLS AB Mouse models have been used to study the mechanisms underlying the carcinogenesis of a wide variety of human cancer. A considerable number of mouse and rat models, used for the study of elementary tumorgenic mechanisms, were found to develop pheochromocytomas. Some of these models resemble hereditary syndrome-related pheochromocytoma in humans and some may serve as a new starting point for human pheochromocytoma research. Recently, we generated a model of catecholamine-producing metastatic pheochromocytoma in athymic nude mice using tail-vein injection of mouse pheochromocytoma cells (MPCs). This and alternative animal models of metastatic pheochromocytoma are promising avenues in preclinical studies to evaluate new therapeutic approaches for malignant pheochromocytoma. C1 NICHD, Unit Clin Neuroendocrinol, RBMB, NIH,CRC, Bethesda, MD 20892 USA. Shinshu Univ, Grad Sch Med, Dept Mol Oncol, Inst Aging & Adaptat, Matsumoto, Nagano 390, Japan. Tufts Univ, Sch Med, Dept Pathol, Tufts New England Med Ctr, Boston, MA 02111 USA. NIMH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHD, Unit Clin Neuroendocrinol, RBMB, NIH,CRC, Bldg 10,Room 1E-3141,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov; karel@mail.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [P01 NS 37685] NR 15 TC 7 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 300 EP 305 DI 10.1196/annals.1353.034 PG 6 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400033 PM 17102099 ER PT S AU Grossman, A Pacak, K Sawka, A Lenders, JWM Harlander, D Peaston, RT Reznek, R Sisson, J Eisenhofer, G AF Grossman, Ashley Pacak, Karel Sawka, Anna Lenders, Jacques W. M. Harlander, Debra Peaston, Robert T. Reznek, Rodney Sisson, James Eisenhofer, Graeme BE Pacak, K Eisenhofer, G TI Biochemical diagnosis and localization of pheochromocytoma - Can we reach a consensus? SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; biochemical diagnosis; metanephrines; catecholamines; localization; computed tomography; magnetic resonance imaging; MIBG; positron emission tomography ID HIPPEL-LINDAU-DISEASE; METAIODOBENZYLGUANIDINE SCINTIGRAPHY; DETECTING PHEOCHROMOCYTOMA; ADRENAL PHEOCHROMOCYTOMA; INITIAL ADRENALECTOMY; PLASMA METANEPHRINES; CLINICAL-EXPERIENCE; SUPPRESSION TEST; CATECHOLAMINES; URINARY AB Pheochromocytomas can have a highly variable presentation, making diagnosis challenging. To think of the tumor represents the crucial initial step, but establishing the diagnosis requires biochemical evidence of excessive catecholamine production and imaging studies to localize the source. Currently, however, there exist no generally agreed upon guidelines based on which tests and testing algorithms should be used to confirm and locate or exclude a suspected pheochromocytoma. Choice of biochemical tests and imaging studies instead usually depends on institutional experience. At the First International Symposium on Pheochromocytoma (ISP2005), held in Bethesda in October 2005, a panel of experts and patient representatives discussed current problems and available options for tumor diagnosis and localization and formulated recommendations, which were subsequently agreed upon by those in attendance at the meeting. This article summarizes the discussion and recommendations derived from that session. C1 St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. St Radboud Hosp, Dept Gen Internal Med, Nijmegen, Netherlands. Pheochromocytoma Support Grp, Camden, NY 13316 USA. Freeman Rd Hosp, Dept Clin Biochem, Newcastle Upon Tyne, Tyne & Wear, England. St Bartholomews Hosp, Div Radiol, London EC1A 7BE, England. Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Grossman, A (reprint author), St Bartholomews Hosp, Dept Endocrinol, London EC1A 7BE, England. EM a.b.grossman@qmul.ac.uk RI Lenders, J.W.M./L-4487-2015 FU Intramural NIH HHS NR 54 TC 57 Z9 61 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 332 EP 347 DI 10.1196/annals.1353.038 PG 16 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400037 PM 17102103 ER PT S AU Shulkin, BL Ilias, I Sisson, JC Pacak, K AF Shulkin, Barry L. Ilias, Ioannis Sisson, James C. Pacak, Karel BE Pacak, K Eisenhofer, G TI Current trends in functional imaging of pheochromocytomas and paragangliomas SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE nuclear medicine methods; radionuclide imaging; positron emission tomography; pheochromocytoma diagnosis ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; MALIGNANT PHEOCHROMOCYTOMA; OCTREOTIDE SCINTIGRAPHY; I-123 METAIODOBENZYLGUANIDINE; EXPRESSING TUMORS; PET; LOCALIZATION; HEAD; NECK AB Most pheochromocytomas/paragangliomas should be evaluated with anatomical imaging (computed tomography or magnetic resonance imaging) followed by functional imaging (nuclear medicine modalities). Functional imaging assures that the tumor is indeed a pheochromocytoma/paraganglioma and enables more thorough localization, especially detecting as many lesions as possible (in particular for metastatic disease). Functional imaging for pheochromocytomas/ paragangliomas, can use radiolabled ligands specific for pathways of synthesis, metabolism, and inactivation of catecholamines or nonspecific ligands. In an overview of the available nuclear medicine modalities, we summarize the accumulated experience and recommend when functional imaging should be applied to patients with pheochromocytoma/paraganglioma. C1 NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Div Nucl Med, Dept Radiol Sci, Memphis, TN 38105 USA. Univ Patras, Sch Med, Dept Pharmacol, GR-26504 Rion, Greece. Univ Michigan, Div Nucl Med, Dept Radiol, Med Ctr, Ann Arbor, MI 48109 USA. RP Pacak, K (reprint author), NICHHD, Sect Med Neuroendocrinol, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,1 E,Room 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov; karel@mail.nih.gov NR 37 TC 30 Z9 32 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 374 EP 382 DI 10.1196/annals.1353.041 PG 9 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400040 PM 17102106 ER PT S AU Martiniova, L Ohta, S Guion, P Schimel, D Lai, EW Klaunberg, B Jagoda, E Pacak, K AF Martiniova, Lucia Ohta, Shoichiro Guion, Peter Schimel, Daniel Lai, Edwin W. Klaunberg, Brenda Jagoda, Elaine Pacak, Karel BE Pacak, K Eisenhofer, G TI Anatomical and functional imaging of tumors in animal models - Focus on pheochromocytoma SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; anatomical imaging; functional imaging; animal model; [F-18]-6F-dopamine ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; THYROID-CARCINOMA; RAT-BRAIN; PET; LOCALIZATION; EXPRESSION; REGISTRATION; HUMANS; MICE AB This review focuses on anatomical (computed tomography, magnetic resonance imaging) and functional (positron emission tomography) imaging methods for tumor localization and identification of experimentally induced tumors in animal models, especially pheochromocytoma. Although anatomical imaging can precisely locate primary and metastatic tumors, functional imaging has high specificity for some tumors, especially those of endocrine origin. This is due to the fact that endocrine tumor cells take up hormone precursors, express hormone receptors and transporters, and synthesize, store, and release hormones. These characteristic properties of endocrine tumors enable investigators to create highly specific radiopharmaceuticals, particularly for positron emission tomography. For example, localization of pheochromocytoma involves [F-18]-6F-dopamine. It is a highly specific radiopharmaceutical since it uses the norepinephrine transporter system expressed in most pheochromocytoma cells. Here we review both anatomical and functional imaging methods that are used conjointly in order to localize and identify specific characteristics of tumors. C1 NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NINDS, Mouse Imaging Facil, Chalk River Labs, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, Intramural Sci PRGMS, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NIH, Bldg 10,Room 1E3140,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM karel@mail.nih.gov; karel@mail.nih.gov FU Intramural NIH HHS NR 42 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 392 EP 404 DI 10.1196/annals.1353.043 PG 13 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400042 PM 17102108 ER PT S AU Koch, CA Gimm, O Vortmeyer, AO Al-Ali, HK Lamesch, P Ott, R Kluge, R Bierbach, U Tannapfel, A AF Koch, Christian A. Gimm, Oliver Vortmeyer, Alexander O. Al-Ali, Haifa K. Lamesch, Peter Ott, Rudolf Kluge, Regine Bierbach, Uta Tannapfel, Andrea BE Pacak, K Eisenhofer, G TI Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy? SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE neuroendocrine; tumor; pheochromocytoma; imatinib; neurofibromatosis type 1 ID IMATINIB MESYLATE; NEUROBLASTIC TUMORS; PHEOCHROMOCYTOMA; CARCINOMA; RECEPTOR; MUTATIONS; TISSUES; PROTEIN; CANCER; CELLS AB Neuroendoerine tumors are very heterogeneous, develop from a variety of tissues, and can be difficult to diagnose. Without the clinical manifestation of metastases, it is often difficult to characterize them as malignant. Even so-called completely (110) resected tumors can spread clinically visible metastases within a few months after initial surgery. Treatment options for neuroendocrine tumors including pheochromocytoma are limited. Molecular targeted therapies using tyrosine kinase inhibitors might prove to be helpful in patients with these tumors. In an immunohistochemical study, we examined KIT in 26 pheochromocytomas, 8 of which were malignant (3 adrenal pheochromocytomas, 5 paragangliomas). KIT expression was found in one of these 8 malignant tumors. This 2.5-cm-large adrenal pheochromocytoma originated from a woman with neurofibromatosis type I and spread into spine, skull, and lung. KIT expression could be demonstrated in 5% of tumor cells. On the basis of KIT expression immunohistochemically, we treated patients with neuroendocrine (i.e., medullary thyroid cancer) and other tumors with imatinib 400 mg per day, but without efficacy after 2 months of therapy. Similar results were shown by other investigators. Therefore, monotherapy with imatinib may not be efficacious in patients with neuroendocrine tumors that express KIT. Tyrosine kinase inhibitors such as sorafenib that targets several receptors in addition to KIT may be more efficacious in treating patients with neuroendocrine tumors. C1 Univ Leipzig, Div Endocrinol & Nephrol, D-7010 Leipzig, Germany. Univ Halle Wittenberg, Dept Surg, Halle, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Div Hematol & Oncol, D-7010 Leipzig, Germany. Sankt Georg Hosp, Dept Surg, Leipzig, Germany. Univ Leipzig, Dept Surg 2, D-7010 Leipzig, Germany. Univ Leipzig, Dept Nucl Med, D-7010 Leipzig, Germany. Univ Leipzig, Div Pediat Hematol & Oncol, D-7010 Leipzig, Germany. Ruhr Univ Bochum, D-4630 Bochum, Germany. RP Koch, CA (reprint author), Univ Mississippi, Div Endocrinol, 2500 N State St, Jackson, MS 39216 USA. EM ckoch@medicine.umsmed.edu RI Koch, Christian/A-4699-2008; al-ali, haifa kathrin/B-3390-2014; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 44 TC 17 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 517 EP 526 DI 10.1196/annals.1353.055 PG 10 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400054 PM 17102120 ER PT S AU Anouar, Y Yon, L Guillemot, J Thouennon, E Barbier, L Gimenez-Roqueplo, AP Bertherat, J Lefebvre, H Klein, M Muresan, M Grouzmann, E Plouin, PF Vaudry, H Elkahloun, AG AF Anouar, Youssef Yon, Laurent Guillemot, Johann Thouennon, Erwan Barbier, Laure Gimenez-Roqueplo, Anne-Paule Bertherat, Jerome Lefebvre, Herve Klein, Marc Muresan, Mihaela Grouzmann, Eric Plouin, Pierre-Francois Vaudry, Hubert Elkahloun, Abdel G. BE Pacak, K Eisenhofer, G TI Development of novel tools for the diagnosis and prognosis of pheochromocytoma using peptide marker immunoassay and gene expression profiling approaches SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE chromogranin A; expression profiling; markers; peptide; secretogranin II; pheochromocytoma ID II-DERIVED PEPTIDE; ADRENAL-GLANDS; PITUITARY; IDENTIFICATION; TUMORS AB Pheochromocytomas (PHEOs) are rare catecholamine-producing neoplasias that arise from chromaffin cells of the adrenal medulla or from extra-adrenal locations. These neuroendocrine tumors are usually benign, but may also present as or develop into a malignancy. There are currently no means to predict or to cure malignant tumors which have a poor prognosis. We have recently validated several assays for the measurement of peptides derived from chromogranin A (CgA) and secretogranin 11 (SgII) in order to determine whether these secreted neuroendocrine products could provide useful, complementary markers for the diagnosis and prognosis of PHEOs. Both the CgA-derived peptide WE14 and the SgII-derived peptide EM66 proved to be sensitive circulating markers for the diagnosis of PHEO. In addition, much higher EM66 levels were measured in benign than in malignant tumoral tissues, suggesting that this peptide could represent a valuable tool for the prognosis of PHEO. We have also initiated a comparative microarray study of benign and malignant PHEOs, which allowed the identification of a set of about 100 genes that were differentially expressed and best discriminated the two types of tumors. A large majority of these genes were expressed at lower levels in the malignant disease and were associated with various characteristics of chromaffin cells, such as hormone secretion signaling and machinery, peptide maturation, and cellular morphology. Altogether, these studies provide novel tools for the management of PHEO, and new insights for the understanding of tumorigenesis in chromaffin cells, which may offer potential therapeutic strategies. C1 Univ Rouen, INSERM, U413, Lab Cellular & Mol Neurodendocrinol,IFRMP23,Europ, F-76821 Mont St Aignan, France. Hop Europeen Georges Pompidou, Dept Genet, Paris, France. INSERM, Dept Endocrinol, U567, Inst Cochin Genet Mol, Paris, France. Hop Brabois, Dept Endocrinol, Nancy, France. CHU Vaudois, Div Clin Pharmacol & Toxicol, CH-1011 Lausanne, Switzerland. Hop Europeen Georges Pompidou, Hypertens Unit, Paris, France. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Anouar, Y (reprint author), Univ Rouen, INSERM, U413, Lab Cellular & Mol Neurodendocrinol,IFRMP23,Europ, F-76821 Mont St Aignan, France. EM youssef.anouar@univ-rouen.fr RI Guillemot, Johann/O-1066-2013; OI Guillemot, Johann/0000-0002-5902-9188; Klein, Marc/0000-0002-1037-4220 NR 13 TC 20 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 533 EP 540 DI 10.1196/annals.1353.057 PG 8 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400056 PM 17102122 ER PT S AU Brouwers, FM Elkahloun, AG Munson, PJ Eisenhofer, G Barb, J Linehan, WM Lenders, JWM De Krijger, R Mannelli, M Udelsman, R Ocal, IT Shulkin, BL Bornstein, SR Breza, J Ksinantova, L Pacak, K AF Brouwers, Frederieke M. Elkahloun, Abdel G. Munson, Peter J. Eisenhofer, Graeme Barb, Jennifer Linehan, W. Marston Lenders, Jacques W. M. De Krijger, Ronald Mannelli, Massimo Udelsman, Robert Ocal, Idris T. Shulkin, Barry L. Bornstein, Stefan R. Breza, Jan Ksinantova, Lucia Pacak, Karel BE Pacak, K Eisenhofer, G TI Gene expression profiling of benign and malignant pheochromocytoma SO PHEOCHROMOCYTOMA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Symposium on Pheochromocytoma CY OCT 20-23, 2005 CL Bethesda, MD SP NIH DE pheochromocytoma; paraganglioma; gene expression; microarray; metastases; catecholamines ID FAMILIAL PHEOCHROMOCYTOMA; PLASMA; PARAGANGLIOMA; MUTATIONS; HYPOXIA AB There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes predisposing to the tumor. Correcting for the confounding influence of noradrenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype-phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers. C1 NICHHD, Reprod Biol & Med Branch, Inst Child Hlth & Human Dev, NIH,CRC, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. St Radboud Hosp, Dept Internal Med, Nijmegen, Netherlands. Erasmus MC Univ, Dept Pathol, Josephine Nefkens Inst, NL-3000 DR Rotterdam, Netherlands. Univ Florence, Dept Clin Pathophysiol, Florence, Italy. Yale Univ, Dept Surg, New Haven, CT 06520 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. Univ Dresden, Dept Med, Dresden, Germany. Comenius Univ, Dept Urol, Bratislava, Slovakia. BIONT, PET Ctr, Bratislava, Slovakia. RP Pacak, K (reprint author), NICHHD, Reprod Biol & Med Branch, Inst Child Hlth & Human Dev, NIH,CRC, Room 1E-1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov; karel@mail.nih.gov RI Lenders, J.W.M./L-4487-2015; OI Mannelli, Massimo/0000-0002-8001-9857 FU Intramural NIH HHS NR 17 TC 46 Z9 46 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-597-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1073 BP 541 EP 556 DI 10.1196/annals.1353.058 PG 16 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFD27 UT WOS:000241140400057 PM 17102123 ER PT J AU Michelman-Ribeiro, A Nossal, R Morris, R Lange, S Kuo, CS Bansil, R AF Michelman-Ribeiro, A Nossal, R Morris, R Lange, S Kuo, CS Bansil, R TI Electrolysis induces pH gradients and domain orientation in agarose gels SO PHYSICAL REVIEW E LA English DT Article ID TRANSIENT ELECTRIC BIREFRINGENCE; SECRETORY GRANULE MATRIX; RAPID STRUCTURAL-CHANGES; NERVE-FIBERS; ELECTROPHORESIS; SCATTERING; FIELDS; POLYMER; LIGHT; DNA AB We have used small-angle light-scattering (SALS), microscopy, and pH measurements to study structural changes produced in unbuffered agarose gels as ions migrate under applied electric fields (3-20 V/cm). Anisotropic, bowtielike, light-scattering patterns were observed, whose development occurred more quickly at higher fields. The horizontal lobes were more pronounced at higher polymer concentration. Analysis of the SALS data with a simple model of scattering from anisotropic rods in an electric field is consistent with anisotropic rodlike domains on the order of 10-15 mu m in length, which align perpendicular to the electric field. The anisotropic domains in the gel reach almost the same level of orientation, regardless of the field strength. Microscope imaging revealed anisotropic domains on the same length scale, also aligned perpendicular to the field. Profiles of pH variation across the gel, measured by video photography, indicate that the anisotropic patterns appear when the H+ and OH- ions, migrating in opposite directions, meet. Calculations of pH profiles using a model based on electrodiffusion reproduce several features of measured pH profiles, including the power-law dependence on the electric field of the time at which the oppositely charged fronts meet. Ions migrating from both ends of the gel produce pH changes that are correlated with macroscopic shrinking and orientation of the gel. C1 Boston Univ, Dept Phys, Boston, MA 02215 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Bansil, R (reprint author), Boston Univ, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. RI Morris, Ryan/G-8560-2013 NR 31 TC 0 Z9 0 U1 1 U2 4 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD JAN PY 2006 VL 73 IS 1 AR 011410 DI 10.1103/PhysRevE.73.011410 PN 1 PG 10 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 007YX UT WOS:000235008500038 ER PT J AU Krsek, M Rosicka, M Nedvidkova, J Kvasnickova, H Hana, V Marek, J Haluzik, M Lai, EW Pacak, K AF Krsek, M. Rosicka, M. Nedvidkova, J. Kvasnickova, H. Hana, V. Marek, J. Haluzik, M. Lai, E. W. Pacak, K. TI Increased lipolysis of subcutaneous abdominal adipose tissue and altered noradrenergic activity in patients with Cushing's syndrome: An in-vivo microdialysis study SO PHYSIOLOGICAL RESEARCH LA English DT Article DE cortisol; catecholamines; noradrenaline; glycerol; fat ID SYMPATHETIC NERVOUS-SYSTEM; RAT-BRAIN; PARAVENTRICULAR NUCLEUS; GROWTH-HORMONE; HUMANS; CORTISOL; NOREPINEPHRINE; HYPERCORTISOLEMIA; CATECHOLAMINES; OBESITY AB Cushing's syndrome is associated with typical central redistribution of adipose tissue. The aim of the study was to assess lipolysis and catecholamines and their metabolites in subcutaneous abdominal adipose tissue using an in-vivo microdialysis technique. Nine patients with Cushing's syndrome and nine age-, gender- and body mass index (BMI)-matched control subjects were included in the study. Local glycerol concentrations were significantly increased in subcutaneous adipose tissue of patients with Cushing's syndrome (p < 0.001). Plasma noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine were decreased in patients with Cushing's syndrome (p < 0.02, p < 0.05, and p < 0.02, respectively). Adrenaline, noradrenaline, dihydroxyphenylglycol and dihydroxyphenylalanine concentrations in subcutaneous abdominal adipose were non-significantly higher in patients with Cushing's syndrome. In conclusion, we showed that lipolysis in subcutaneous adipose tissue of patients with Cushing's syndrome is significantly increased as compared to healthy subjects. This finding together with non- significantly increased local catecholamine concentrations in these patients suggests a possible link between increased lipolysis and catecholaminergic activity in subcutaneous adipose tissue. C1 Charles Univ, Fac Med 1, Dept Med 3, Prague 12808 2, Czech Republic. Inst Endocrinol, Prague, Czech Republic. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Krsek, M (reprint author), Charles Univ, Fac Med 1, Dept Med 3, U Nemocnice 1, Prague 12808 2, Czech Republic. EM mkrse@lf1.cuni.cz RI Marek, Josef/S-6166-2016 OI Marek, Josef/0000-0002-3257-2025 NR 34 TC 15 Z9 18 U1 0 U2 0 PU ACAD SCIENCES CZECH REPUBLIC, INST PHYSIOLOGY PI PRAGUE 4 PA VIDENSKA 1083, PRAGUE 4 142 20, CZECH REPUBLIC SN 0862-8408 J9 PHYSIOL RES JI Physiol. Res. PY 2006 VL 55 IS 4 BP 421 EP 428 PG 8 WC Physiology SC Physiology GA 078SX UT WOS:000240124800009 PM 16238457 ER PT J AU Chadwick, LR Pauli, GF Farnsworth, NR AF Chadwick, LR Pauli, GF Farnsworth, NR TI The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties SO PHYTOMEDICINE LA English DT Review DE Humulus lupulus; pharmacognosy; pharmacology; estrogenic properties ID POSTMENOPAUSAL HORMONE-THERAPY; HUMAN LIVER-MICROSOMES; PLANT-EXTRACTS; RECEPTOR-BETA; POTENT PHYTOESTROGEN; MENOPAUSAL SYMPTOMS; REPLACEMENT THERAPY; MASS-SPECTROMETRY; ESSENTIAL OILS; BEER AB As the population ages, there is an ever-increasing need for therapeutic agents that can be used safely and efficaciously to manage symptoms related to postmenopausal estrogen deficiency. Endogenous estrogens, e.g., 17 beta-estradiol, of exogenous mammalian origin, e.g., horses, have long been used to manage such symptoms. There are more than 20 different classes of phytochemicals that have demonstrated affinity for human estrogen receptors in vitro. Some studies on exogenous estrogenic substances of botanical origin (phytoestrogens), such as standardized formulations of plant extracts with in vitro and in vivo estrogenic activity from soy (Glycine max Merill.) and red clover (Trifolium pratense L.), suggest clinical efficacy. Few clinical data for phytoestrogens other than isoflavonoids are available. In an exhaustive review of the literature through 2003, only two clinical trials were identified that were designed to evaluate the effect of hops (Humulus lupulus L.) on symptoms related to menopause. Folkloric, chemical, and biological literature relating primarily to the use of hops for their estrogenic activity, and two human clinical trials, are reviewed. (c) 2005 Elsevier GmbH. All rights reserved. C1 Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Coll Pharm, Chicago, IL 60612 USA. RP Chadwick, LR (reprint author), Kalsec Inc, POB 50511, Kalamazoo, MI 49005 USA. EM lchadwick@kalsec.com OI Pauli, Guido/0000-0003-1022-4326 FU NCCIH NIH HHS [P50 AT000155, P50 AT000155-070001, P50 AT00155] NR 136 TC 81 Z9 89 U1 8 U2 39 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 J9 PHYTOMEDICINE JI Phytomedicine PD JAN PY 2006 VL 13 IS 1-2 BP 119 EP 131 DI 10.1016/j.phymed.2004.07.006 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 010NE UT WOS:000235200600017 PM 16360942 ER PT J AU Arteaga, C Alava, C Sanchez, M Diaz, E Aragon, M Cortes, C Bermudez, JA AF Arteaga, C Alava, C Sanchez, M Diaz, E Aragon, M Cortes, C Bermudez, JA TI Evaluation of histopathology criteria, DNA polimorphism and gene expression for the diagnosis of gestational trophoblastic disease SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Maternal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Nacl Colombia, Dept Obstet & Gynecol, Bogota, Colombia. Univ Nacl Colombia, Fac Sci, Bogota, Colombia. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A40 EP A40 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200137 ER PT J AU Tapia, A Gangi, L Zegers-Hochschild, F Balmaceda, J Pommer, P Trejo, L Pacheco, I Salvatierra, A Henriquez, S Quezada, M Vargas, M Croxatto, HB Velasquez, L AF Tapia, A Gangi, L Zegers-Hochschild, F Balmaceda, J Pommer, P Trejo, L Pacheco, I Salvatierra, A Henriquez, S Quezada, M Vargas, M Croxatto, HB Velasquez, L TI Searching genes involved in human endometrial infertility SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Mateanal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Santiago Chile, Dept Biol, Santiago, Chile. NCI, Lab Mol Technol, Sci Applicat Int Corp, Frederick, MD USA. Clin Las Condes, Unidad Med Reprod, Santiago, Chile. U Chile, IDIMI, Santiago, Chile. Millenium Inst Fundamental & Appl Biol, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A10 EP A10 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200040 ER PT J AU Vargas, M Velasquez, L Gangi, L Monroe, D Salvatierra, DM Croxatto, H AF Vargas, M Velasquez, L Gangi, L Monroe, D Salvatierra, DM Croxatto, H TI Effect of levonorgestrel on mRNA transcript levels in the human endometrium during the window of implantation SO PLACENTA LA English DT Meeting Abstract CT Joint Meeting of the 2nd Latinamerican Symposium on Fetal-Mateanal Interaction and Placenta/19th Annual Meeting of the Chilean-Society-of-Physiological-Sciences CY NOV 06-09, 2005 CL Santiago, CHILE SP Chilean Soc Physiol Sci C1 Univ Santiago Chile, Dept Biol, Santiago, Chile. NCI, Bethesda, MD 20892 USA. Millenium Inst Fundamental & Appl Biol, Santiago, Chile. Inst Chileno Med Reprod, Santiago, Chile. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD JAN PY 2006 VL 27 IS 1 BP A10 EP A10 PG 1 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 993YM UT WOS:000233996200041 ER PT S AU Nelson, K AF Nelson, Karin BE Baker, P Sibley, C TI The placenta and neurological outcome in the child SO Placenta and Neurodisability SE CLINICS IN DEVELOPMENTAL MEDICINE LA English DT Proceedings Paper CT Conference on Placenta and Neurodisability CY 2003 CL Manchester, ENGLAND ID FETAL THROMBOTIC VASCULOPATHY; PRENATAL BRAIN-DAMAGE; NORMAL BIRTH-WEIGHT; V-LEIDEN MUTATION; CEREBRAL-PALSY; PRETERM INFANTS; TERM INFANTS; ULTRASOUND ABNORMALITIES; NEONATAL ENCEPHALOPATHY; REACTION PATTERNS C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Nelson, K (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. NR 59 TC 1 Z9 1 U1 0 U2 0 PU MAC KEITH PRESS PI LONDON PA 30 FURNIVAL STREET, LONDON EC4A 1JQ, ENGLAND SN 0069-4835 BN 1-898683-44-1 J9 CLIN DEV MED PY 2006 VL 169 BP 1 EP 13 PG 13 WC Clinical Neurology; Obstetrics & Gynecology; Pediatrics SC Neurosciences & Neurology; Obstetrics & Gynecology; Pediatrics GA BEM26 UT WOS:000238119000001 ER PT J AU Rajagopalan, S Bryceson, YT Kuppusamy, SP Geraghty, DE van der Meer, A Joosten, I Long, EO AF Rajagopalan, S Bryceson, YT Kuppusamy, SP Geraghty, DE van der Meer, A Joosten, I Long, EO TI Activation of NK cells by an endocytosed receptor for soluble HLA-G SO PLOS BIOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; IFN-GAMMA PRODUCTION; LEUKOCYTE ANTIGEN-G; KIR2DL4 CD158D; T-CELLS; SIGNAL-TRANSDUCTION; FUNCTIONAL TRANSFER; DIRECT BINDING; CUTTING EDGE; EXPRESSION AB Signaling from endosomes is emerging as a mechanism by which selected receptors provide sustained signals distinct from those generated at the plasma membrane. The activity of natural killer (NK) cells, which are important effectors of innate immunity and regulators of adaptive immunity, is controlled primarily by receptors that are at the cell surface. Here we show that cytokine secretion by resting human NK cells is induced by soluble, but not solid-phase, antibodies to the killer cell immunoglobulin-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen (HLA)- G. KIR2DL4 was constitutively internalized into Rab5-positive compartments via a dynamin-dependent process. Soluble HLA-G was endocytosed into KIR2DL4 - containing compartments in NK cells and in 293T cells transfected with KIR2DL4. Chemokine secretion induced by KIR2DL4 transfection into 293T cells occurred only with recombinant forms of KIR2DL4 that trafficked to endosomes. The profile of genes up-regulated by KIR2DL4 engagement on resting NK cells revealed a proinflammatory/proangiogenic response. Soluble HLA-G induced secretion of a similar set of cytokines and chemokines. This unique stimulation of resting NK cells by soluble HLA-G, which is endocytosed by KIR2DL4, implies that NK cells may provide useful functions at sites of HLA-G expression, such as promotion of vascularization in maternal decidua during early pregnancy. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Fred Hutchinson Canc Res Ctr, Washington, DC USA. Radboud Univ Nijmegen, Nijmegen Med Ctr, Dept Blood Transfus & Transplantat Immunol, Nijmegen, Netherlands. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM eLong@nih.gov RI Joosten, Irma/D-2374-2010; Long, Eric/G-5475-2011; Joosten, Irma/N-4418-2013; van der Meer, Arnold/M-1693-2016; OI Long, Eric/0000-0002-7793-3728; Joosten, Irma/0000-0003-2950-4977; van der Meer, Arnold/0000-0001-8274-414X; Bryceson, Yenan/0000-0002-7783-9934 FU Intramural NIH HHS NR 75 TC 189 Z9 201 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2006 VL 4 IS 1 BP 70 EP 86 AR e9 DI 10.1371/journal.pbio.0040009 PG 17 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 003DY UT WOS:000234663000008 PM 16366734 ER PT J AU Traherne, JA Horton, R Roberts, AN Miretti, M Hurles, ME Stewart, CA Ashurst, JL Atrazhev, AM Coggill, P Palmer, S Almeida, J Sims, S Wilming, LG Rogers, J de Jong, PJ Carrington, M Elliott, JF Sawcer, S Todd, JA Trowsdale, J Beck, S AF Traherne, James A. Horton, Roger Roberts, Anne N. Miretti, MarcosM. Hurles, Matthew E. Stewart, C. Andrew Ashurst, Jennifer L. Atrazhev, Alexey M. Coggill, Penny Palmer, Sophie Almeida, Jeff Sims, Sarah Wilming, Laurens G. Rogers, Jane de Jong, Pieter J. Carrington, Mary Elliott, John F. Sawcer, Stephen Todd, John A. Trowsdale, John Beck, Stephan TI Genetic analysis of completely sequenced disease-associated MHC haplotypes identifies shuffling of segments in recent human history SO PLOS GENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II REGION; SINGLE-NUCLEOTIDE POLYMORPHISMS; DIABETES SUSCEPTIBILITY GENES; LINKAGE-DISEQUILIBRIUM MAP; HUMAN GENOME; MULTIPLE-SCLEROSIS; OVERDOMINANT SELECTION; MEIOTIC RECOMBINATION; HLA-C AB The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC) cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2) and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms ( SNPs). Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II-related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (< 3,400 generations). These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of ancestral blocks via recombination is a potential mechanism whereby certain DR-DQ allelic combinations, which presumably have favoured immunological functions, can spread across haplotypes and populations. C1 Wellcome Trust Sanger Inst, Cambridge, England. Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1TN, England. Univ Cambridge, Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab, Juvenile Diabet Res Fdn, Cambridge CB2 1TN, England. Univ Alberta, Dept Med Microbiol & Immunol, Div Dermatol & Cutaneous Sci, Alberta Diabet Inst, Edmonton, AB T6G 2M7, Canada. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. SAIC Frederick Inc, Natl Canc Inst, Lab Genom Divers, Basic Res Program, Frederick, MD USA. Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 1TN, England. RP Beck, S (reprint author), Wellcome Trust Sanger Inst, Genome Campus, Cambridge, England. EM beck@sanger.ac.uk RI Todd, John/A-3542-2010; Stewart, Charles/G-2470-2012; xu, tao/K-6631-2016; OI Wilming, Laurens/0000-0002-4154-7358; Almeida-King, Jeff/0000-0002-3716-4880 FU NCI NIH HHS [N01CO12400, N01-CO-12400]; Wellcome Trust [048880] NR 89 TC 98 Z9 100 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD JAN PY 2006 VL 2 IS 1 BP 81 EP 92 AR E9 DI 10.1371/journal.pgen.0020009 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 069WY UT WOS:000239481100008 PM 16440057 ER PT J AU Graham, BS AF Graham, BS TI New approaches to vaccine adjuvants: Inhibiting the inhibitor SO PLOS MEDICINE LA English DT Editorial Material ID VIRUS C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgraham@nih.gov NR 9 TC 9 Z9 9 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2006 VL 3 IS 1 BP 18 EP 20 AR e57 DI 10.1371/journal.pmed.0030057 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 026MJ UT WOS:000236342700006 PM 16383350 ER PT J AU Hartley, DM Morris, JG Smith, DL AF Hartley, DM Morris, JG Smith, DL TI Hyperinfectivity: A critical element in the ability of V.cholerae to cause epidemics? SO PLOS MEDICINE LA English DT Article ID VIBRIO-CHOLERAE AB Background Cholera is an ancient disease that continues to cause epidemic and pandemic disease despite ongoing efforts to limit its spread. Mathematical models provide one means of assessing the utility of various proposed interventions. However, cholera models that have been developed to date have had limitations, suggesting that there are basic elements of cholera transmission that we still do not understand. Methods and Findings Recent laboratory findings suggest that passage of Vibrio cholerae O1 Inaba El Tor through the gastrointestinal tract results in a short-lived, hyperinfectious state of the organism that decays in a matter of hours into a state of lower infectiousness. Incorporation of this hyperinfectious state into our disease model provides a much better fit with the observed epidemic pattern of cholera. These findings help to substantiate the clinical relevance of laboratory observations regarding the hyperinfectious state, and underscore the critical importance of human-to-human versus environment-to-human transmission in the generation of epidemic and pandemic disease. Conclusions To have maximal impact on limiting epidemic spread of cholera, interventions should be targeted toward minimizing risk of transmission of the short-lived, hyperinfectious form of toxigenic Vibrio cholerae. The possibility of comparable hyperinfectious states in other major epidemic diseases also needs to be evaluated and, as appropriate, incorporated into models of disease prevention. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Hartley, DM (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. EM dhartley@epi.umaryland.edu RI Smith, David/L-8850-2013; OI Smith, David/0000-0003-4367-3849; Hartley, David/0000-0001-5202-6278; , David/0000-0003-2589-2538 FU NIAID NIH HHS [K25 AI-58956, K25 AI058956] NR 19 TC 143 Z9 148 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JAN PY 2006 VL 3 IS 1 BP 63 EP 69 AR e7 DI 10.1371/journal.pmed.0030007 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 026MJ UT WOS:000236342700015 PM 16318414 ER PT J AU Sumby, P Whitney, AR Graviss, EA Deleo, FR Musser, JM AF Sumby, Paul Whitney, Adeline R. Graviss, Edward A. DeLeo, Frank R. Musser, James M. TI Genome-wide analysis of group A streptococci reveals a mutation that modulates global phenotype and disease specificity SO PLOS PATHOGENS LA English DT Article AB Many human pathogens produce phenotypic variants as a means to circumvent the host immune system and enhance survival and, as a potential consequence, exhibit increased virulence. For example, it has been known for almost 90 y that clinical isolates of the human bacterial pathogen group A streptococci ( GAS) have extensive phenotypic heterogeneity linked to variation in virulence. However, the complete underlying molecular mechanism(s) have not been defined. Expression microarray analysis of nine clinical isolates identified two fundamentally different transcriptomes, designated pharyngeal transcriptome profile (PTP) and invasive transcriptome profile (ITP). PTP and ITP GAS differed in approximately 10% of the transcriptome, including at least 23 proven or putative virulence factor genes. ITP organisms were recovered from skin lesions of mice infected subcutaneously with PTP GAS and were significantly more able to survive phagocytosis and killing by human polymorphonuclear leukocytes. Complete genome resequencing of a mouse-derived ITP GAS revealed that the organism differed from its precursor by only a 7-bp frameshift mutation in the gene (covS) encoding the sensor kinase component of a two-component signal transduction system implicated in virulence. Genetic complementation, and sequence analysis of covR/S in 42 GAS isolates confirmed the central role of covR/S in transcriptome, exoproteome,and virulence modulation. Genome-wide analysis provides a heretofore unattained understanding of phenotypic variation and disease specificity in microbial pathogens, resulting in new avenues for vaccine and therapeutics research. C1 Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Ctr Human Bacterial Pathogenesis Res, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, 6535 Fannin, Houston, TX 77030 USA. EM jmmusser@tmh.tmc.edu NR 0 TC 229 Z9 231 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2006 VL 2 IS 1 BP 41 EP 49 AR e5 DI 10.1371/journal.ppat.0020005 PG 9 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA V42VD UT WOS:000202894100005 PM 16446783 ER PT J AU Hou, J Seth, P Major, EO AF Hou, J Seth, P Major, EO TI JC virus can infect human immune and nervous system progenitor cells: Implications for pathogenesis SO POLYOMAVIRUSES AND HUMAN DISEASES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; NUCLEAR FACTOR-I; STEM-CELLS; HUMAN BRAIN; HUMAN POLYOMAVIRUS; BONE-MARROW; EXPRESSION; DISEASE; PROTEIN; MULTIPLICATION AB Recent finite self renewal and pluripotentiality as stem cells are, progenitor cells can give rise to cells of different lineages. It is infection of these differentiated cells that has traditionally been associated with the pathology and symptoms of viral-induced disease. However, neural progenitor cells have been shown, in vitro, to be susceptible to infection by neurotropic viruses such as the human polyomavirus, JCV, and the lentivirus, HIV-1. These progenitor cells, which exist during development as well as in the fully developed adult brain, could therefore be involved in neuropathogenesis. Morever, JCV can also infect progenitor cells of the hematopoictic system, derivatives of which have been implicated in the trafficking of virus from the periphery to the bra-in. Interestingly, susceptibility to and molecular regulation of JCV infection in hematopoietic cells closely parallels what has been observed in glial cells. The biological interaction between the immune and nervous systems that exists in the dissemination of virus from periphery to nervous system and the susceptibility of both systems to JCV infection provide potential for hematopoietic and neural progenitor cell involvement in JCV pathogenesis. C1 NINDS, NIH, Bethesda, MD 20892 USA. Natl Brain Res Ctr, Manesar, Haryana, India. RP Hou, J (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 31 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 577 BP 266 EP 273 PG 8 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BDZ78 UT WOS:000236353100019 PM 16626042 ER PT J AU Tien, ES Hannon, DB Thompson, JT Heuvel, JPV AF Tien, Eric S. Hannon, Daniel B. Thompson, Jerry T. Heuvel, John P. Vanden TI Examination of Ligand-Dependent Coactivator Recruitment by Peroxisome Proliferator-Activated Receptor-alpha (PPAR alpha) SO PPAR RESEARCH LA English DT Article AB The ligand-dependent recruitment of coactivators to peroxisome proliferator-activated receptor-alpha (PPAR alpha) was examined. PPAR-binding protein (PBP), PPAR gamma coactivator-1 alpha (PGC-1 alpha), steroid receptor coactivator-1 (SRC-1), and CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) affected PPAR alpha activity in the presence of Wy-14,643. The effects on PPAR alpha activity in light of increased or decreased expression of these coactivators were qualitatively different depending on the ligand examined. Diminished expression of PGC-1 alpha, SRC-1, or PBP by RNAi plasmids affected natural or synthetic agonist activity whereas only Wy-14,643 was affected by decreased PGC-1 alpha. The interaction of PPAR alpha with an LXXLL-containing peptide library showed ligand-specific patterns, indicative of differences in conformational change. The association of coactivators to PPAR alpha occurs predominantly via the carboxyl-terminus and mutating (456)LHPLL to (456)LHPAA resulted in a dominant-negative construct. This research confirms that coactivator recruitment to PPAR alpha is ligand-dependent and that selective receptor modulators (SRMs) of this important protein are likely. Copyright (C) 2006 Eric S. Tien et al. C1 [Tien, Eric S.; Hannon, Daniel B.; Thompson, Jerry T.; Heuvel, John P. Vanden] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Tien, Eric S.; Hannon, Daniel B.; Thompson, Jerry T.; Heuvel, John P. Vanden] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Tien, Eric S.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Tien, ES (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 201 Life Sci Bldg, University Pk, PA 16802 USA. NR 31 TC 7 Z9 7 U1 1 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2006 AR 69612 DI 10.1155/PPAR/2006/69612 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13LR UT WOS:000207668800001 ER PT J AU Reed, DB Birnbaum, A Brown, LH O'Connor, RE Fleg, JL Peberdy, MA Van Ottingham, L Hallstrom, AP AF Reed, David B. Birnbaum, Alice Brown, Lawrence H. O'Connor, Robert E. Fleg, Jerome L. Peberdy, Mary A. Van Ottingham, Lois Hallstrom, Alfred P. CA PAD Trial Investigators TI Location of cardiac arrests in the Public Access Defibrillation Trial SO PREHOSPITAL EMERGENCY CARE LA English DT Article DE public-access defibrillation; cardiac arrest; survival; automated external defibrillator ID AUTOMATED EXTERNAL DEFIBRILLATOR; COST-EFFECTIVENESS; UNITED-STATES; SURVIVAL; DEATH; OUTCOMES AB Background. The Public Access Defibrillation ( PAD) Trial found an overall doubling in the number of out-of-hospital cardiac arrest ( CA) survivors when a lay responder team was equipped with an automated external defibrillator (AED), compared with cardiopulmonary resuscitation (CPR) alone. Objectives. To describe the types of facilities that participated in the trial and to report the incidence of CA and survival in these different types of facilities. Methods. In this posthoc analysis of PAD Trial data, the physical characteristics of the participating facilities and the numbers of presumed CAs, treatable CAs, and survivors are reported for each category of facilities. Results. There were 625 presumed CAs at 1,260 participating facilities. Just under half (n = 291) of the presumed CAs were classified as treatable CAs. Treatable CAs occurred at a rate of 2.9 per 1,000 person-years of exposure; rates were highest in fitness centers (5.1) and golf courses (4.8) and lowest in office complexes (0.7) and hotels ( 0.7). Survival from treatable CA was highest in recreational complexes (0.5), public transportation sites (0.4), and fitness centers ( 0.4) and lowest in office complexes (0.1) and residential facilities (0.0). Conclusions. During the PAD Trial, the exposure-adjusted rate of treatable CA was highest in fitness centers and golf courses, but the incidence per facility was low to moderate. Survival from treatable cardiac arrest was highest in recreational complexes, public transportation facilities, and fitness centers. C1 SUNY Syracuse, Upstate Med Univ, Dept Emergency Med, Syracuse, NY 13210 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Christiana Hlth Care Serv, Dept Emergency Med, Newark, DE USA. NHLBI, Div Epidemiol & Clin Applicat, Clin Trials Sci Res Grp, Bethesda, MD 20892 USA. Virginia Commonwealth Univ Hlth Syst, Dept Emergency Med, Richmond, VA USA. Virginia Commonwealth Univ Hlth Syst, Dept Med, Richmond, VA USA. RP Reed, DB (reprint author), SUNY Syracuse, Upstate Med Univ, Dept Emergency Med, 750 E Adams St,Jacobsen Hall,9th Floor, Syracuse, NY 13210 USA. NR 32 TC 19 Z9 21 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1090-3127 J9 PREHOSP EMERG CARE JI Prehosp. Emerg. Care PD JAN-MAR PY 2006 VL 10 IS 1 BP 61 EP 67 DI 10.1080/10903120500366128 PG 7 WC Emergency Medicine; Public, Environmental & Occupational Health SC Emergency Medicine; Public, Environmental & Occupational Health GA 110IX UT WOS:000242373000010 PM 16526143 ER PT S AU Hursting, SD Cantwell, MM Sansbury, LB Forman, MR AF Hursting, SD Cantwell, MM Sansbury, LB Forman, MR BE Lucas, A Sampson, HA TI Nutrition and cancer prevention: Targets, strategies, and the importance of early life interventions SO Primary Prevention by Nutrition Intervention in Infancy and Childhood SE NESTLE NUTRITION WORKSHOP SERIES PEDIATRIC PROGRAM LA English DT Proceedings Paper CT 57th Nestle Pediatric Nutrition Workshop CY MAY, 2005 CL San Francisco, CA ID GROWTH-FACTOR-I; UMBILICAL-CORD SERUM; DEPENDENT DIABETES-MELLITUS; FACTOR-BINDING PROTEIN-1; SKIN TUMOR PROMOTION; INFANT BIRTH-WEIGHT; DNA EXCISION-REPAIR; BREAST-CANCER; UNITED-STATES; FETAL-GROWTH C1 NCI, Lab Biosyst & Canc, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hursting, SD (reprint author), NCI, Lab Biosyst & Canc, Ctr Canc Res, Bethesda, MD 20892 USA. NR 252 TC 3 Z9 3 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0742-2806 BN 3-8055-7978-0 J9 NESTLE NUTR WORKS SE PY 2006 VL 57 BP 153 EP 202 DI 10.1159/000091072 PG 50 WC Nutrition & Dietetics; Pediatrics SC Nutrition & Dietetics; Pediatrics GA BDY53 UT WOS:000236177300011 PM 16632966 ER PT B AU Ressom, HW Varghese, RS Orvisky, E Drake, SK Hortin, GL Abdel-Hamid, M Loffredo, CA Goldman, R AF Ressom, H. W. Varghese, R. S. Orvisky, E. Drake, S. K. Hortin, G. L. Abdel-Hamid, M. Loffredo, C. A. Goldman, R. GP IEEE TI Biomarker identification and rule extraction from mass spectral serum profiles SO PROCEEDINGS OF THE 2006 IEEE SYMPOSIUM ON COMPUTATIONAL INTELLIGENCE IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY LA English DT Proceedings Paper CT IEEE Symposium on Computational Intelligence in Bioinformatics and Computational Biology CY SEP 28-29, 2006 CL Toronto, CANADA ID HEPATOCELLULAR-CARCINOMA; PATTERN-CLASSIFICATION; OVARIAN-CANCER; EXPRESSION; SPECTROMETRY; ALGORITHMS; INDUCTION; DISCOVERY; MODELS AB In this paper, we introduce a novel feature selection method that combines ant colony optimization (ACO) with support vector machine (SVM) to identify candidate biomarkers from mass spectral serum profiles. In addition, we present an innovative rule extraction algorithm that uses ACO to select accurate IF-THEN rules for the classification of mass spectra. We applied the proposed feature selection and rule extraction methods to identify candidate biomarkers and extract IF-THEN classification rules from MALDI-TOF spectra of enriched serum. The candidate biomarkers and the associated rules distinguished hepatocellular carcinoma patients from matched controls with high sensitivity and specificity. C1 [Ressom, H. W.; Varghese, R. S.; Orvisky, E.; Loffredo, C. A.; Goldman, R.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20057 USA. [Drake, S. K.; Hortin, G. L.] NIH, Dept Lab Med, Clin Chem Serv, Bethesda, MD 20892 USA. [Abdel-Hamid, M.] NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. RP Ressom, HW (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20057 USA. RI Varghese, Rency/A-8770-2012 FU U.S. Army Medical Research and Material Command, Prostate Cancer Research [DAMD17-02-1-0057]; American Cancer Society [CRTG-02-245-01-CCE] FX This work was supported in part by U.S. Army Medical Research and Material Command, Prostate Cancer Research Program grant DAMD17-02-1-0057 and American Cancer Society grant CRTG-02-245-01-CCE awarded to RG. NR 29 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 1-4244-0623-4 PY 2006 BP 164 EP + PG 2 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA BFW23 UT WOS:000245066100023 ER PT B AU Ogurtsov, AY Vasilchenko, AN Vasov, PK Shabalina, SA Kondrashov, AS Roytberg, MA AF Ogurtsov, A. Yu Vasilchenko, A. N. Vasov, P. K. Shabalina, S. A. Kondrashov, A. S. Roytberg, M. A. BE Kolchanov, N Hofestadt, R TI Owen-script - An extended tool for pairwise genome alignment SO Proceedings of the Fifth International Conference on Bioinformatics of Genome Regulation and Structure, Vol 1 LA English DT Proceedings Paper CT 5th International Conference on Bioinformatics of Genome Regulation and Structure CY JUL 16-22, 2006 CL Novosibirsk, RUSSIA SP Inst Cytol & Genet, Lab Theoret Genet, Inst Cytol & Genet, Siberian Branch Russian Acad Sci, Vavilov Soc Genet & Breeders, Russian Acad Sci, Sci Council Bioinformat, Siberian Branch, Russian Acad Sci, Siberian Branch, Novosibirsk State Univ, Dept Natl Sci, Chair Informat Biol DE pairwise alignment; genomes; hierarchical approach ID COLLINEAR REGIONS; DIVERGENCE; DNA AB Motivation: A genome alignment is an important instrument of post-genomic computational biology. The commonly available tools (LAGAN, BLAT, YASS, etc) designed for command line mode and thus tend to loose some similarities without any possibility for user to learn about this. In contrast, the OWEN is an interactive tool, allowing user to control the alignment process and to be sure that no interesting events were lost. However, one may need tools to store some alignment protocols that are suitable for a class of similar situations and then implement the protocol automatically. Results: We propose OWEN-SCRIPT, an extension of the OWEN program thet al.lows to perform OWEN based scripts. The commands of the scripts correspond to the actions of interactive OWEN. Examples of protocols obtained from alignment human and mouse genomes are also available. C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Ogurtsov, AY (reprint author), Natl Ctr Biotechnol Informat, NIH, 45 Ctr Dr, Bethesda, MD 20892 USA. RI Shabalina, Svetlana/N-8939-2013; Roytberg, Mikhail/O-1299-2013 OI Shabalina, Svetlana/0000-0003-2272-7473; Roytberg, Mikhail/0000-0002-5848-367X NR 9 TC 0 Z9 0 U1 0 U2 0 PU RUSSIAN ACAD SCI SIBERIAN BRANCH PI NOVOSIBIRSK PA NOVOSKIBRISK 90, MORSKOI, PROSP 2, 630090 NOVOSIBIRSK, RUSSIA BN 978-5-7692-0846-1 PY 2006 BP 122 EP 125 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFQ54 UT WOS:000243856400027 ER PT B AU Miller, ERP AF Miller, E. R. P., III GP Medimond TI High dose vitamin E supplementation and mortality: Discussion of the results of a meta-analysis of randomized controlled clinical trial SO Proceedings of the XIII Congress of the Society for Free Radical Research International LA English DT Proceedings Paper CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int C1 NIA, Baltimore, MD 21224 USA. RP Miller, ERP (reprint author), NIA, Baltimore, MD 21224 USA. NR 1 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 88-7587-274-0 PY 2006 BP 15 EP 16 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFP22 UT WOS:000243558800003 ER PT B AU Huang, KP Huang, FL Shetty, PK AF Huang, K. -P. Huang, F. L. Shetty, P. K. GP Medimond TI Oxidant-induced modification of PKC by reactive sulfur species: Glutathione disulfide S-oxides SO Proceedings of the XIII Congress of the Society for Free Radical Research International LA English DT Proceedings Paper CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int ID PROTEIN-KINASE-C; SUPEROXIDE; ACTIVATION AB Treatment of mouse brain synaptosomes with oxidants caused an increase in protein glutathionylation and PKC aggregation. These responses were hypothesized to be mediated in part by two reactive sulfur species, glutathione disulfide S-monoxide (GS-DSMO) and -dioxide (GS-DSDO). These two disulfide S-oxides (DSOs) were synthesized by metal ion-catalyzed oxidation of GSH with H2O2 and they exhibited distinct specificity toward PKC. GS-DSMO caused PKC beta aggregation with low stoichiometry of thionylation (similar to 1 mole/mole) and a small degree of inhibition; whereas, GS-DSDO caused a higher degree of thionylation (similar to 4-5 mole/mole) and extensive inhibition of the kinase. These DSOs were much more potent than GSSG and GSNO to modify PKC and were potential mediators for the oxidant-induced modification of protein. C1 NICHHD, Endocrinol & Reprod Res Branch, Metab Regulat Sect, NIH, Bethesda, MD 20892 USA. RP Huang, KP (reprint author), NICHHD, Endocrinol & Reprod Res Branch, Metab Regulat Sect, NIH, Bethesda, MD 20892 USA. NR 12 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 88-7587-274-0 PY 2006 BP 159 EP 165 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFP22 UT WOS:000243558800028 ER PT B AU Noda, Y Berlett, B Stadtman, ER Aponte, A Morgan, M Shen, RF AF Noda, Y. Berlett, B. Stadtman, E. R. Aponte, A. Morgan, M. Shen, R. -F. GP Medimond TI Identification of enzymes and regulatory proteins in E. coli that are preferentially oxidized under nitrogen or carbon starvation SO Proceedings of the XIII Congress of the Society for Free Radical Research International LA English DT Proceedings Paper CT 13th Biennial Meeting of the Society-for-Free-Radical-Research-International CY AUG 15-19, 2006 CL Davos, SWITZERLAND SP Soc Free Rad Res Int ID OXIDATION AB The uniquely oxidized proteins in E. coli grown in aerobic condition under nitrogen (N)- or carbon (C)-starvation were identified by proteomic analysis. The oxidized proteins were detected by 2, 4-dinitrophenolhydrazine (DNPH) and 2-D immuno-Western blot. The 2-DE separation by narrow pH range immobiline DryStrip pH (5-6) for the first dimension allowed detecting proteins as single spots. It was found that under N-starvation, protein carbonyls were highly accumulated in 48 h stationary phase, and particularly more than 30 proteins were more prone to oxidative modification. C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Noda, Y (reprint author), NHLBI, Biochem Lab, Bldg 3, Bethesda, MD 20892 USA. NR 4 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 88-7587-274-0 PY 2006 BP 261 EP 264 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFP22 UT WOS:000243558800049 ER PT S AU Aebig, JA Albert, HH Zhu, BL Hu, JS Hsu, HT AF Aebig, J. A. Albert, H. H. Zhu, B. L. Hu, J. S. Hsu, H. T. BE Chang, CA Cheng, YH TI Cloning and construction of single-chain variable fragments (scFv) to Cucumber mosaic virus and production of transgenic plants SO Proceedings of the XIth International Symposium on Virus Diseases of Ornamental Plants SE ACTA HORTICULTURAE LA English DT Proceedings Paper CT 11th International Symposium on Virus Diseases of Ornamental Plants CY MAR 09-14, 2004 CL Taichung, TAIWAN SP Council Agr, Execut Yuan, Bur Anim & Plant Hlth Inspect & Quarantine, Council Agr, Agr Res Inst, Council Agr, Natl Museum Nat Sci, Taiwan Phytopathol Soc, Wellbond Sci, Bion Tech, Tekfa Sci, Unimed Healthcare, Taiwan Cymbidium Assoc, Keybond Technol, Sun Kuan Instruments Co Sunrise, Biotechnology Co, Taida Hort Co DE disease resistance; monoclonal antibodies; immunoglobulin genes ID NICOTIANA-BENTHAMIANA; COAT PROTEIN; EXPRESSION; ANTIBODY; TABACUM AB The variable regions of heavy and light chain genes were cloned from the RNA of mouse hybridoma cells that produce monoclonal antibodies specific to Cucumber mosaic virus (CMV). The cloned genes were constructed into single-chain variable fragments (scFv) in combination with various promoters and transferred into Nicotiana benthamiana leaf tissue using Agrobacterium tumefacien. Transgenic plants were generated and selected using the bar gene that confers resistance to phosphinothricin. From purified genomic plant DNA, the scFv was re-cloned after PCR and sequenced to verify the presence of the transgene. Resistance to CMV infection was evaluated by mechanically inoculating plants with purified CMV. Several R0 transgenic plants exhibited some degree of disease resistance in the first screening, showing no symptoms, reduced symptoms or delayed symptom development. In subsequent challenge inoculations of RI plants with lower dilutions of inoculum, occasionally plants showed resistance when compared with nontransformed plants, but, overall, results were variable. For each of the four promoters, three or four transgenic plants were generated exhibiting some degree of disease resistance. C1 NIAID, NIH, MVDU, Rockville, MD 20850 USA. RP Aebig, JA (reprint author), NIAID, NIH, MVDU, 5640 Fishers Lane, Rockville, MD 20850 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU INTERNATIONAL SOCIETY HORTICULTURAL SCIENCE PI LEUVEN 1 PA PO BOX 500, 3001 LEUVEN 1, BELGIUM SN 0567-7572 BN 978-90-6605-649-7 J9 ACTA HORTIC PY 2006 IS 722 BP 129 EP 135 PG 7 WC Horticulture SC Agriculture GA BFP37 UT WOS:000243587800016 ER PT J AU Baek, SJ Eling, TE AF Baek, SJ Eling, TE TI Changes in gene expression contribute to cancer prevention by COX inhibitors SO PROGRESS IN LIPID RESEARCH LA English DT Review DE COX; NSAIDs; NAG-1; MIC-1; GDF-15; LOX; AA ID TGF-BETA SUPERFAMILY; DRUG-ACTIVATED GENE; BONE MORPHOGENETIC PROTEIN; GROWTH-FACTOR-BETA; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTATE CARCINOMA-CELLS; HUMAN COLORECTAL-CANCER; CYCLOOXYGENASE INHIBITORS; COLON CARCINOGENESIS; EPITHELIAL-CELLS AB Non-steroidal anti-inflammatory drugs (NSAIDs) are used primarily for the treatment of inflammatory diseases. However, certain NSAIDs also have a chemopreventive effect on the development of human colorectal and other cancers. NSAIDs inhibit cyclooxygenase-1 (COX-1) and/or cyclooxygenase-2 (COX-2) activity and considerable evidence supports a role for prostaglandins in cancer development. However, the chemopreventive effect of NSAIDs on colorectal and other cancers appears also to be partially independent of COX activity. COX inhibitors also alter the expression of a number of genes that influence cancer development. One such gene is NAG-1 (NSAID-Activated Gene), a critical gene regulated by a number of COX inhibitors and chemopreventive chemicals. Therefore, this article will discuss the evidence supporting the conclusion that the chemo-preventive activity of COX inhibitors is mediated, in part, by altered gene expression with an emphasis on NAG-I studies. This review may also provide new insights into how chemicals and environmental factors influence cancer development. In view of the cardiovascular and gastrointestinal toxic side effects of COX-2 inhibitors and non-selective COX inhibitors, respectively, the results presented here may provide the basis for the development of a new family of anti-tumorigenic compounds acting independent of COX inhibition. Published by Elsevier Ltd. C1 NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA. RP Eling, TE (reprint author), NIEHS, NIH, Mol Carcinogenesis Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM cling@niehs.nih.gov OI Baek, Seung/0000-0001-7866-7778 FU NIEHS NIH HHS [ES011657] NR 72 TC 49 Z9 51 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7827 J9 PROG LIPID RES JI Prog. Lipid Res. PD JAN PY 2006 VL 45 IS 1 BP 1 EP 16 DI 10.1016/j.plipres.2005.10.001 PG 16 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 015VH UT WOS:000235578800001 PM 16337272 ER PT S AU Hatfield, DL Carlson, BA Xu, XM Mix, H Gladyshev, VN AF Hatfield, Dolph L. Carlson, Bradley A. Xu, Xue-Ming Mix, Heiko Gladyshev, Vadim N. BE Moldave, K TI Selenocysteine incorporation machinery and the role of selenoproteins in development and health SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 81 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review; Book Chapter ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; TYPE-2 IODOTHYRONINE DEIODINASE; INSERTION-SEQUENCE ELEMENTS; NONSENSE-MEDIATED DECAY; MESSENGER-RNA LEVELS; SERINE TRANSFER-RNA; DIETARY SELENIUM; MAMMALIAN SELENOPROTEIN; TRANSFER RNASEC; GENETIC-CODE C1 NCI, Mol Biol Seleium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Seleium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RI Gladyshev, Vadim/A-9894-2013 FU Intramural NIH HHS NR 148 TC 117 Z9 121 U1 2 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 BN 0-12-540081-0 J9 PROG NUCLEIC ACID RE JI Prog. Nucl. Res. Molec. Biol. PY 2006 VL 81 BP 97 EP 142 DI 10.1016/S0079-6603(06)81003-2 PG 46 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFC94 UT WOS:000241029900003 PM 16891170 ER PT S AU Pommier, Y Barcelo, JA Rao, VA Sordet, O Jobson, AG Thibaut, L Miao, ZH Seiler, JA Zhang, H Marchand, C Agama, K Nitiss, JL Redon, C AF Pommier, Yves Barcelo, Juana A. Rao, V. Ashutosh Sordet, Olivier Jobson, Andrew G. Thibaut, Laurent Miao, Ze-Hong Seiler, Jennifer A. Zhang, Hongliang Marchand, Chrstophe Agama, Keli Nitiss, John L. Redon, Christophe BE Moldave, K TI Repair of topoisomerase I - Mediated DNA damage SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 81 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review; Book Chapter ID DOUBLE-STRAND BREAKS; CHK2 PROTEIN-KINASE; S-PHASE CHECKPOINT; RNA-POLYMERASE-II; CAMPTOTHECIN-INDUCED APOPTOSIS; TELANGIECTASIA-MUTATED ATM; SISTER-CHROMATID COHESION; MOLECULAR INTERACTION MAP; CROSS-LINKING AGENTS; DIOL EPOXIDE ADDUCTS C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RI Nitiss, John/E-9974-2010; Sordet, Olivier/M-3271-2014; Marchand, Christophe/D-8559-2016; OI Nitiss, John/0000-0002-1013-4972 FU Intramural NIH HHS [Z99 CA999999] NR 266 TC 126 Z9 127 U1 0 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 BN 0-12-540081-0 J9 PROG NUCLEIC ACID RE JI Prog. Nucl. Res. Molec. Biol. PY 2006 VL 81 BP 179 EP + DI 10.1016/S0079-6603(06)81005-6 PG 52 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFC94 UT WOS:000241029900005 PM 16891172 ER PT J AU Wistow, G AF Wistow, G TI The NEIBank project for ocular genomics: Data-mining gene expression in human and rodent eye tissues SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID RETINAL-PIGMENT EPITHELIUM; SEQUENCE TAG ANALYSIS; GAMMA-D-CRYSTALLIN; HUMAN TRABECULAR MESHWORK; OPEN-ANGLE GLAUCOMA; 6000 NONREDUNDANT TRANSCRIPTS; MIGRATION INHIBITORY FACTOR; AQUAPORIN WATER CHANNELS; FACTOR-H POLYMORPHISM; GROWTH-FACTOR AB NETBank is a project to gather and organize genomic resources for eye research. The first phase of this project covers the construction and sequence analysis of cDNA libraries from human and animal model eye tissues to develop an overview of the repertoire of genes expressed in the eye and a resource of cDNA clones for further studies. The sequence data are grouped and identified using the tools of bioinformatics and the results are displayed through a web site where they can be interrogated by keyword search, chromosome location, by Blast (sequence comparison) or by alignment on completed genomes. Many novel proteins and novel splice forms of known genes have already emerged from analysis of the accumulating data. This review provides an overview of the current state of the database for human eye tissues, with specific comparisons to some parallel data from mouse and rat, and with illustrative examples of the kinds of insights and discoveries these data can produce. One of the major themes that emerges is that at the molecular level human eye tissues have significant differences from those of rodents, encompassing species specific genes, alternative splice forms and great variation in levels of gene expression. These point to specific adaptations and mechanisms in the human eye and emphasize that care needs to be taken in the application of appropriate animal model systems. (c) 2005 Elsevier Ltd. All rights reserved. C1 Natl Inst Hlth, Sect Mol Struct & Funct Genom, Natl Eye Inst, Bethesda, MD 20892 USA. RP Natl Inst Hlth, Sect Mol Struct & Funct Genom, Natl Eye Inst, Bldg 7,Room 201, Bethesda, MD 20892 USA. EM graeme@helix.nih.gov NR 219 TC 27 Z9 31 U1 0 U2 1 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 2006 VL 25 IS 1 BP 43 EP 77 DI 10.1016/j.preteyeres.2005.05.003 PG 35 WC Ophthalmology SC Ophthalmology GA 989SA UT WOS:000233692900003 PM 16005676 ER PT B AU Kolenbrander, P AF Kolenbrander, Paul BE Dworkin, M Falkow, S Rosenberg, E Schleifer, KH Stackebrandt, E TI The Genus Veillonella SO PROKARYOTES: A HANDBOOK ON THE BIOLOGY OF BACTERIA, VOL 4, THIRD EDITION: BACTERIA: FIRMICUTES, CYANOBACTERIA LA English DT Article; Book Chapter ID METHYLMALONYL-COA DECARBOXYLASE; VENTILATOR-ASSOCIATED PNEUMONIA; PROSTHETIC VALVE ENDOCARDITIS; HUMAN EXPERIMENTAL GINGIVITIS; LENGTH POLYMORPHISM ANALYSIS; NEGATIVE ANAEROBIC-BACTERIA; POLYMERASE-CHAIN-REACTION; GRAM-POSITIVE BACTERIA; SOFT-TISSUE INFECTIONS; HUMAN DENTAL PLAQUE C1 NIDR, NIH, Bethesda, MD 20892 USA. RP Kolenbrander, P (reprint author), NIDR, NIH, Bethesda, MD 20892 USA. NR 194 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-25494-4 PY 2006 BP 1022 EP 1040 DI 10.1007/0-387-30744-3_36 D2 10.1007/0-387-30744-3 PG 19 WC Microbiology SC Microbiology GA BKJ68 UT WOS:000268326600036 ER PT J AU Tam, NNC Nyska, A Maronpot, RR Kissling, G Lomnitski, L Suttie, A Bakshi, S Bergman, M Grossman, S Ho, SM AF Tam, NNC Nyska, A Maronpot, RR Kissling, G Lomnitski, L Suttie, A Bakshi, S Bergman, M Grossman, S Ho, SM TI Differential attenuation of oxidative/nitrosative injuries in early prostatic neoplastic lesions in TRAMP mice by dietary antioxidants SO PROSTATE LA English DT Article DE prostate cancer; oxidative stress; nitrosative stress; TRAMP model; dietary antioxidants ID WATER-SOLUBLE ANTIOXIDANT; GREEN TEA POLYPHENOLS; OXIDATIVE DNA-DAMAGE; CARCINOMA-CELLS; CANCER RISK; NATURAL ANTIOXIDANTS; TRANSGENIC MOUSE; REACTIVE OXYGEN; MODEL; EXPRESSION AB BACKGROUND. Dietary antioxidants with yet unproven efficacies in averting prostate cancer (PCa) are widely used in the United States as preventives. Experimental evidence establishing a causal relationship between oxidative and nitrosative stress (OS/NS) and PCa development and showing its modulation by dietary antioxidants would help justify their usage. METHODS. The TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) mouse model was used to demonstrate the OS/NS-associated damage, as evident by 8-hydroxy-2'deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE)-protein-adducts and nitrotyrosine (Ntyr), in prostatic premalignant lesions, and to evaluate the antioxidant efficacy of various dietary supplements [natural antioxidant (NAO) from spinach extracts, (-) epigallocatechin-3-gallate (EGCG), or N-acetylcystein (NAC)] during the early PCa development. RESULT. We show, for the first time, that oxidative/nitrosative damages of genomic DNA and cellular proteins were discretely localized in premalignant lesions, but not in adjacent morphologically normal epithelia, of TRAMP prostates; these injuries were absent in age-matched nontransgenic littermates. The extent of OS/NS-related injuries correlated well with the tempo of development and prevalence of premalignant lesions in various prostatic lobes and exhibited a clear trend of increase from 12 to 20 weeks of age. Treatment of TRAMP mice with various antioxidants as dietary supplements resulted in differential alleviation of OS/NSrelated prostatic injuries. The antioxidant potencies of the dietary supplements did not fully correlate with their documented antiPCa actions, suggest that they may exert additional "nonantioxidant," antitumor effects in this model. CONCLUSIONS. Our data indicate that in TRAMP mice, OS/NS injuries are likely involved in early prostatic tumorigenesis and can be modulated by various antioxidants. C1 Univ Massachusetts, Sch Med, Dept Surg, Div Urol, Worcester, MA 01605 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. ILS, Res Triangle Pk, NC USA. Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Ho, SM (reprint author), Univ Massachusetts, Sch Med, Dept Surg, Div Urol, Rm 504,Lazare Res Bldg,364 Plantat St, Worcester, MA 01605 USA. EM Shuk-mei.Ho@umassmed.edu FU NCI NIH HHS [CA15776, CA62269]; NIDDK NIH HHS [DK61084] NR 63 TC 31 Z9 32 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-4137 J9 PROSTATE JI Prostate PD JAN 1 PY 2006 VL 66 IS 1 BP 57 EP 69 DI 10.1002/pros.20313 PG 13 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 995RL UT WOS:000234121400006 PM 16114064 ER PT J AU Tycko, R AF Tycko, R TI Solid-state NMR as a probe of amyloid structure SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE amyloid structure; Alzheimer's disease; prions; protein aggregation; magnetic resonance ID NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; BETA-SHEET STRUCTURE; PROTEIN SECONDARY STRUCTURE; FIBRIL FORMATION; CHEMICAL-SHIFT; ALZHEIMERS-DISEASE; PRION PROTEIN; MOLECULAR-STRUCTURE; CORE STRUCTURE AB Solid state nuclear magnetic resonance (NMR) has developed into one of the most informative and direct experimental approaches to the characterization of the molecular structures of amyloid fibrils, including those associated with Alzheimer's disease. In this article, essential aspects of solid state NMR methods are described briefly and results obtained to date regarding the supramolecular organization of amyloid fibrils and the conformations of peptides within amyloid fibrils are reviewed. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm 112, Bethesda, MD 20892 USA. EM robertty@niddk.nih.gov FU NIDDK NIH HHS [Z01 DK029029-09] NR 96 TC 28 Z9 28 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PY 2006 VL 13 IS 3 BP 229 EP 234 DI 10.2174/092986606775338470 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 017XE UT WOS:000235725800004 PM 16515450 ER PT J AU Nallamsetty, S Waugh, DS AF Nallamsetty, S Waugh, DS TI Solubility-enhancing proteins MBP and NusA play a passive role in the folding of their fusion partners SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE maltose-binding protein; NusA; solubility enhancer; solubility tag; affinity tag; fusion protein; inclusion bodies; passenger protein ID MALTOSE-BINDING-PROTEIN; HIGH-LEVEL EXPRESSION; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI; MOLECULAR CHAPERONE; PURIFICATION; CYTOPLASM; RECEPTOR; SYSTEM AB It is well established that certain highly soluble proteins have the ability to enhance the solubility of their fusion partners. However, very little is known about how different solubility enhancers compare in terms of their ability to promote the proper folding of their passenger proteins. We compared the ability of two well-known solubility enhancers, Escherichia coli maltose-binding protein (MBP) and N utilization substance A (NusA), to improve the Solubility and promote the proper folding of a variety of passenger proteins that are difficult to solubilize. We used an intracellular processing system to monitor the solubility of these passenger proteins after they were cleaved from MBP and NUsA by tobacco etch virus protease. In addition, the biological activity of some fusion proteins was compared to serve as a more quantitative indicator of native structure. The results indicate that MBP and NusA have comparable solubility-enhancing properties. Little or no difference was observed either in the solubility of passenger proteins after intracellular processing of the MBP and NusA fusion proteins or in the biological activity of solubilized passenger proteins, suggesting that the underlying mechanism of solubility enhancement is likely to be similar for both the proteins, and that they play a passive role rather than an active one in the folding of their fusion partners. Published by Elsevier Inc. C1 NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21701 USA. EM waughd@ncifcrf.gov NR 28 TC 105 Z9 112 U1 2 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JAN PY 2006 VL 45 IS 1 BP 175 EP 182 DI 10.1016/j.pep.2005.06.012 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 001GH UT WOS:000234521100022 PM 16168669 ER PT J AU Bielnicki, J Devedjiev, Y Derewenda, U Dauter, Z Joachimiak, A Derewenda, ZS AF Bielnicki, J Devedjiev, Y Derewenda, U Dauter, Z Joachimiak, A Derewenda, ZS TI B-subtilis ykuD protein at 2.0 A resolution: Insights into the structure and function of a novel, ubiquitous family of bacterial enzymes SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE hydrolase; crystal structure; catalytic triad; structural genomics; protein crystallization ID STAPHYLOCOCCUS-AUREUS; CELL-WALL; CRYSTAL-STRUCTURE; BINDING-PROTEINS; SURFACE PROTEIN; LYSM DOMAIN; SORTASE-B; CATALYSIS; MODEL; SITE AB The crystal structure of the product of the Bacillus subtilis ykuD gene was solved by the multiwavelength anomalous dispersion (MAD) method and refined using data to 2.0 angstrom resolution. The ykuD protein is a representative of a distinctly prokaryotic and ubiquitous family found among both pathogenic and nonpathogenic Gram-positive and Gram-negative bacteria. The deduced amino acid sequence reveals the presence of an N-terminal LysM domain, which occurs among enzymes involved in cell wall metabolism, and a novel, putative catalytic domain with a highly conserved His/Cys-containing motif of hitherto unknown structure. As the wild-type protein did not crystallize, a double mutant was designed (Lys117A1a/Gln118Ala) to reduce excess surface conformational entropy. As expected, the structure of the LysM domain is similar to the NMR structure reported for an analogous domain from Escherichia coli murein transglycosylase MUD. The molecular model also shows that the 112-residue-long C-terminal domain has a novel tertiary fold consisting of a beta-sandwich with two mixed sheets, one containing five strands and the other, six strands. The two beta-sheets form a cradle capped by an a-helix. This domain contains a putative catalytic site with a tetrad of invariant His123, Gly124, Cys139, and Arg141. The stereochemistry of this active site shows similarities to peptidotransferases and sortases, and suggests that the enzymes of the ykuD family may play an important role in cell wall biology. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. NCI, Synchrotron Radiat Res Sect, Argonne Natl Lab, Argonne, IL USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. Argonne Natl Lab, Struct Biol Ctr, Argonne, IL 60439 USA. RP Derewenda, ZS (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, POB 00736, Charlottesville, VA 22908 USA. EM zsd4n@virginia.edu FU NIGMS NIH HHS [P50 GM062414-02, GM62615, P-50-GM62414, P50 GM062414, R01 GM062615] NR 33 TC 53 Z9 56 U1 1 U2 6 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 PD JAN 1 PY 2006 VL 62 IS 1 BP 144 EP 151 DI 10.1002/prot.20702 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 000CN UT WOS:000234438600014 PM 16287140 ER PT J AU Rossi, L Martin, BM Hortin, GL White, RL Foster, M Moharram, R Stroncek, D Wang, E Marincola, FM Panelli, MC AF Rossi, L Martin, BM Hortin, GL White, RL Foster, M Moharram, R Stroncek, D Wang, E Marincola, FM Panelli, MC TI Inflammatory protein profile during systemic high dose interleukin-2 administration SO PROTEOMICS LA English DT Article DE acute phase reactant; interleukin-2; nephelometry; renal cancer; SELDI-TOF MS ID SERUM-AMYLOID-A; C-REACTIVE PROTEIN; ACUTE-PHASE RESPONSE; HUMAN ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; RECOMBINANT INTERLEUKIN-2; CANCER-PATIENTS; SAA GENE; RENAL-CANCER; INDUCTION AB Systemic interleukin-2 (IL-2) administration induces an assortment of downstream effects whose biological and therapeutic significance remains unexplored mostly because of the methodological inability to globally address their complexity. Protein array analysis of sera from patients with renal cell carcinoma obtained prior and during high-dose IL-2 therapy had previously revealed extensive alterations in expression of the soluble factors analyzed, whose discovery was limited by the number of capture antibodies selected for protein detection. Here, we expanded the analysis to SELDI-TOF-MS and quantitative protein analysis (nephelometry). All cytokines/chemokines detected by protein arrays were below the SELDI detection limit, while novel IL-2-specific changes in expression of acute-phase reactants and high-density lipoprotein metabolites could be identified. Serum amyloid protein A (SAA) and C-reactive protein expression were consistently up-regulated after four doses of IL-2, while other proteins were downregulated. These findings were confirmed by SELDI immunoaffinity capture and nephelometry. Immunoaffinity capture revealed different, otherwise undetectable, isoforms of SAA. A linear correlation between peak area by SELDI and protein concentration by nephelometry was observed. Overall distinct yet complementary information was obtained using different platforms, which may better illustrate complex phenomena such as the systemic response to biological response modifiers. C1 NIH, Dept Transfus Med, Immunogenet Sect, Ctr Clin, Bethesda, MD 20892 USA. Univ Pisa, Dept Human Morphol & Appl Biol, Pisa, Italy. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. Carolinas Blumenthal Canc Ctr, Charlotte, NC USA. RP Panelli, MC (reprint author), NIH, Dept Transfus Med, Immunogenet Sect, Ctr Clin, Bldg 10,Room 1C-711,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. EM mpanelli@mail.cc.nih.gov NR 52 TC 32 Z9 36 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JAN PY 2006 VL 6 IS 2 BP 709 EP 720 DI 10.1002/pmic.200500004 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 010PX UT WOS:000235207700032 PM 16342236 ER PT J AU Meyers, BS AF Meyers, BS TI This issue: Psychotic depression SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. Cornell Univ, Program Clin Epidemiol & Hlth Serv, Grad Sch Med Sci, Ithaca, NY 14853 USA. New York Presbyterian Hosp Payne Whitney N, White Plains, NY USA. NIMH, Study Pharmacotherapy Psychot Depress, Bethesda, MD 20892 USA. RP Meyers, BS (reprint author), Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. NR 7 TC 1 Z9 1 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JAN PY 2006 VL 36 IS 1 BP 7 EP + PG 3 WC Psychiatry SC Psychiatry GA 006CP UT WOS:000234873000002 ER PT J AU Lieberman, JA Hsiao, JK AF Lieberman, JA Hsiao, JK TI Interpreting the results of the CATIE study SO PSYCHIATRIC SERVICES LA English DT Letter C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NIMH, Adult Treatment & Prevent Intervent Brach, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Lieberman, JA (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. NR 2 TC 11 Z9 11 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2006 VL 57 IS 1 BP 139 EP 139 DI 10.1176/appi.ps.57.1.139 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 000NN UT WOS:000234469000027 PM 16399980 ER PT S AU Vermetten, E Vythilingam, M Schmahl, C De Kloet, C Southwick, SM Charney, DS Bremner, JD AF Vermetten, Eric Vythilingam, Meena Schmahl, Christian De Kloet, Carien Southwick, Steven M. Charney, Dennis S. Bremner, J. Douglas BE Yehuda, R TI Alterations in stress reactivity after long-term treatment with paroxetine in women with posttraumatic stress disorder SO PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER: A DECADE OF PROGRESS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Psychobiology of Post-Traumatic Stress Disorder CY SEP 11-13, 2005 CL New York, NY SP New York Acad Sci DE cortisol; PTSD; stress; paroxetine; SSRI; challenge; HPA axis ID CORTICOTROPIN-RELEASING HORMONE; URINARY CORTISOL EXCRETION; PITUITARY-ADRENAL AXIS; SUSTAINED CHILDHOOD ABUSE; COMBAT VETERANS; HPA AXIS; MAJOR DEPRESSION; DEXAMETHASONE-SUPPRESSION; GLUCOCORTICOID RECEPTORS; REDUCES RESPONSIVENESS AB Posttraumatic stress disorder (PTSD) is typically accompanied by both acute and chronic alterations in the stress response. These alterations have mostly been described in individuals under baseline conditions, but studies have also used a challenge model to assess the role of the hypothalamic-pituitary-adrenal (HPA) axis in the stress response. The purpose of this article was to assess the effect of long-term treatment with the selective reuptake inhibitor (SSRI), paroxetine, on stress reactivity in patients with PTSD. We assessed diurnal salivary cortisol and urinary cortisol as well as cortisol, heart rate, and behavioral responses to a standardized cognitive stress challenge, in 13 female patients with chronic PTSD before and after 12 months of paroxetine treatment. Treatment resulted in a significant decrease in PTSD symptoms. Twenty-four-hour urinary cortisol was lower compared to base line after successful treatment. Treatment resulted in a decrease of salivary cortisol levels on all time points on a diurnal curve. Despite similar stress perception, cortisol response to the cognitive stress challenge resulted in a 26.5% relative decrease in stress-induced salivary cortisol with treatment. These results suggest that successful treatment with SSRI in chronic PTSD is associated with a trend for a decrease in baseline diurnal cortisol and with reduced cortisol reactivity to stress. C1 Univ Utrecht, Med Ctr, Dept Psychiat, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Cent Inst Mental Hlth, D-68159 Mannheim, Germany. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. W Haven VAMC, Natl Ctr PTSD, West Haven, CT 06516 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Atlanta VAMC, Decatur, GA 30033 USA. RP Vermetten, E (reprint author), Univ Utrecht, Med Ctr, Dept Psychiat, Rudolf Magnus Inst Neurosci, Int Mailbox B0I206,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM e.vermetten@umcutrecht.nl RI Schmahl, C/E-8760-2012; OI Vermetten, Eric/0000-0003-0579-4404 FU NCRR NIH HHS [S10 RR016917, S10 RR016917-01]; NIMH NIH HHS [K24 MH076955-05, 1R01MH56120-01A1, K24 MH076955, R01 MH056120, R01 MH056120-12, T32 MH067547, T32 MH067547-05] NR 74 TC 22 Z9 24 U1 3 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-619-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1071 BP 184 EP 202 DI 10.1196/annals.1364.014 PG 19 WC Multidisciplinary Sciences; Clinical Neurology; Psychiatry SC Science & Technology - Other Topics; Neurosciences & Neurology; Psychiatry GA BFB20 UT WOS:000240653600014 PM 16891570 ER PT B AU Hallett, M AF Hallett, Mark BE Hallet, M Fahn, S Jankovic, J Lang, AE Cloninger, CR Yudofsky, SC TI Voluntary and involuntary movements in humans SO PSYCHOGENIC MOVEMENT DISORDERS: NEUROLOGY AND NEUROPSYCHIATRY SE Neurology Reference Series LA English DT Proceedings Paper CT Conference on Psychogenic Movement Disorders CY OCT 10-13, 2003 CL Atlanta, GA SP Moverment Disorders Soc, Natl Inst Neurol Disorders & Stoke, AstraZeneca, Bristol-Myers Squibb Co, Pfizer Inc, GlaxoSmithkline, Alergan Inc, Ortho-McNeil Pharmaceut, Amarin Pharaceut Inc, UCB Pharma, Wyeth ID POSITRON-EMISSION-TOMOGRAPHY; EXTERNALLY TRIGGERED MOVEMENTS; FUNCTIONAL MAGNETIC-RESONANCE; POTENTIALS; INITIATION; DECEPTION; CORTEX; FMRI; TICS; EXPERIENCE AB Psychogenic movements may be voluntary or involuntary. If voluntary, the mechanism is factitious or malingering and the patient is lying. Most commonly, the movements are conversion or somatization in origin, and are involuntary. The movements look voluntary, however, and the fact that they are preceded by a normal-looking Bereitschaftspotential suggests that they share some brain mechanisms with normal voluntary movement. Perhaps there is an unconscious force that initiates these movements. More likely, the brain just does not interpret them as being voluntary. There is good evidence that the brain generates movements as a result of all the inputs to the motor system, and that the sense of voluntariness is a perception. Physiologic studies are providing information on how this can happen. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 41 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA BN 0-7817-9627-X J9 NEUROL REF SER PY 2006 BP 189 EP 195 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BEN97 UT WOS:000238383000022 ER PT B AU Wise, SP Kralik, JD AF Wise, Steven P. Kralik, Jerald D. BE Hallet, M Fahn, S Jankovic, J Lang, AE Cloninger, CR Yudofsky, SC TI The neurophysiology of voluntary movement in nonhuman primates: Accumulator models of decision and action in relation to psychogenic movement disorders SO PSYCHOGENIC MOVEMENT DISORDERS: NEUROLOGY AND NEUROPSYCHIATRY SE Neurology Reference Series LA English DT Proceedings Paper CT Conference on Psychogenic Movement Disorders CY OCT 10-13, 2003 CL Atlanta, GA SP Moverment Disorders Soc, Natl Inst Neurol Disorders & Stoke, AstraZeneca, Bristol-Myers Squibb Co, Pfizer Inc, GlaxoSmithkline, Alergan Inc, Ortho-McNeil Pharmaceut, Amarin Pharaceut Inc, UCB Pharma, Wyeth ID POSTERIOR PARIETAL CORTEX; DORSOLATERAL PREFRONTAL CORTEX; DEVELOPING OCULOMOTOR COMMANDS; CHIMPANZEES PAN-TROGLODYTES; REVERSED-CONTINGENCY TASK; PERCEPTUAL DECISION; INHIBITORY CONTROL; FRONTAL-CORTEX; RESPONSES; MONKEYS AB According to some recent models of decision, choice, and action, distinct neural networks accumulate evidence in favor of making a potential movement. Voluntary movements arise when one of these "accumulator networks" reaches its threshold for producing an output. Sluggish operations in these networks could prevent an intended movement or make one difficult. Hyperactive accumulators might generate unintended movements. Other networks operate through similar accumulator mechanisms to "veto" movements, and hyperactive operations in these networks could also prevent intended movements. Taken together with the idea that people might be aware of some of the "evidence" for making or vetoing a movement, but not all of it, these models provide useful insights into psychogenic movement disorders. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. NR 58 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA BN 0-7817-9627-X J9 NEUROL REF SER PY 2006 BP 196 EP 211 PG 16 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BEN97 UT WOS:000238383000023 ER PT J AU Costa, PT McCrae, RR AF Costa, PT McCrae, RR TI Age changes in personality and their origins: Comment on Roberts, Walton, and Viechtbauer (2006) SO PSYCHOLOGICAL BULLETIN LA English DT Article DE traits; maturation; meta-analysis; culture; biology ID 5-FACTOR MODEL; STABILITY; TRAITS; ADULTHOOD; CULTURES AB Although B. W. Roberts, K. W. Walton, and W. Viechtbauer (2006) depicted the present authors as proponents of the immutability of traits, in fact we have always acknowledged the possibility of change, and we are pleased that the results of their meta-analysis are consistent with our conclusions about modest change after age 30. We agree with B.W. Roberts et al. that analyses should be conducted at the level of more specific traits, but prefer the 30 facets of the Revised NEO Personality Inventory to the Social Dominance-Social Vitality distinction. The origins of age changes might be found either in environmental influences common to all cultures or in biologically based intrinsic maturation; we offer some reasons for preferring the latter interpretation. Meta-analyses are useful but not definitive, and the resolution of the origin question lies in further research. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, Bethesda, MD 21224 USA. RP Costa, PT (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, Box 03,5600 Nathan Shock Dr, Bethesda, MD 21224 USA. EM costap@grc.nia.nih.gov OI Costa, Paul/0000-0003-4375-1712 NR 28 TC 76 Z9 83 U1 1 U2 23 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD JAN PY 2006 VL 132 IS 1 BP 26 EP 28 DI 10.1037/0033-2909.132.1.26 PG 3 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 007CW UT WOS:000234946500002 PM 16435955 ER PT J AU Bazinet, RP Weis, MT Rapoport, SI Rosenberger, TA AF Bazinet, RP Weis, MT Rapoport, SI Rosenberger, TA TI Valproic acid selectively inhibits conversion of arachidonic acid to arachidonoyl-CoA by brain microsomal long-chain fatty acyl-CoA synthetases: relevance to bipolar disorder SO PSYCHOPHARMACOLOGY LA English DT Article DE valproate; bipolar disorder; arachidonic acid; acyl-CoA synthetase; docosahexaenoic acid; kinetics ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; DOCOSAHEXAENOIC ACID; CHRONIC LITHIUM; PHOSPHOLIPIDS; METABOLISM; TURNOVER; EXPRESSION; DECREASES; COENZYME AB Rational: Several drugs used to treat bipolar disorder (lithium and carbamazepine), when administered chronically to rats, reduce the turnover of arachidonic acid, but not docosahexaenoic acid, in brain phospholipids by decreasing the activity of an arachidonic acid-selective phospholipase A(2). Although chronic valproic acid produces similar effects on brain arachidonic acid and docosahexaenoic acid turnover, it does not alter phospholipase A(2) activity, suggesting that it targets a different enzyme in the turnover pathway. Materials and methods/Results: By isolating rat brain microsomal long-chain fatty acyl-CoA synthetases (Acsl), we show in vitro that valproic acid is a non-competitive inhibitor of Acsl, as it reduces the maximal velocity of the reaction without changing the affinity of the substrate for the enzyme. While valproic acid inhibited the synthesis of arachidonoyl-CoA, palmitoyl-CoA, and docosahexaenoyl-CoA, the K (i) for inhibition of arachidonoyl-CoA synthesis (14.1 mM) was approximately one fifth the K (i) for inhibiting palmitoyl-CoA (85.4 mM) and docosahexaenoyl-CoA (78.2 mM) synthesis. As chronic administration of valproic acid in bipolar disorder achieves whole-brain levels of 1.0 to 1.5 mM, inhibition of arachidonoyl-CoA formation can occur at brain concentrations that are therapeutically relevant to this disease. Furthermore, brain microsomal Acsl did not produce valproyl-CoA. Conclusions: This study shows that valproic acid acts as a non-competitive inhibitor of brain microsomal Acsl, and that inhibition is substrate-selective. The study supports the hypothesis that valproic acid acts in bipolar disorder by reducing the brain arachidonic acid cascade, by inhibiting arachidonoyl-CoA formation. C1 Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58203 USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. RP Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, 501 N Columbia Rd,Rm 3742A, Grand Forks, ND 58203 USA. EM trosenberger@medicine.nodak.edu NR 45 TC 46 Z9 46 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2006 VL 184 IS 1 BP 122 EP 129 DI 10.1007/s00213-005-0272-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 996XC UT WOS:000234208000015 PM 16344985 ER PT J AU Yasar, S Gaal, J Panlilio, LV Justinova, Z Molnar, SV Redhi, GH Schindler, CW AF Yasar, S Gaal, J Panlilio, LV Justinova, Z Molnar, SV Redhi, GH Schindler, CW TI A comparison of drug-seeking behavior maintained by D-amphetamine, L-deprenyl (selegiline), and D-deprenyl under a second-order schedule in squirrel monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE amphetamine; deprenyl; drug self-administration; second-order schedule; selegiline; squirrel monkeys ID OXIDASE-B INHIBITOR; MONOAMINE-OXIDASE; COCAINE INJECTION; FOOD PRESENTATION; MAO-B; RHESUS-MONKEYS; FIXED-RATIO; BRAIN; DOPAMINE; PHENYLETHYLAMINE AB L-Deprenyl ( selegiline) is used in the treatment of Parkinson's disease and has been proposed as an aid for cigarette smoking cessation and a treatment for psycho-stimulant abuse. L-Deprenyl is metabolized in the body to L-methamphetamine and L-amphetamine, suggesting that it may have abuse potential. The current study assessed whether L-deprenyl or its isomer would maintain drug-seeking behavior on a second-order schedule and whether L-deprenyl would alter drug-seeking behavior maintained by D-amphetamine if given as a pretreatment. Squirrel monkeys learned to respond on a second-order schedule of reinforcement, where every tenth response was followed by a brief light flash, and the first brief light flash after 30 min was paired with intravenous (i.v.) injection of D-amphetamine (0.56 mg/kg), administered over a 2-min period at the end of the session. When responding was stable, saline or different i.v. doses of D-amphetamine (0.3-1.0 mg/kg), L-deprenyl (0.1-10.0 mg/kg), and D-deprenyl (0.1-3.0 mg/kg) were substituted for 10 days each. Subsequently, monkeys were pretreated with 0.3 or 1.0 mg/kg L-deprenyl intramuscularly 30 min prior to D-amphetamine baseline sessions. D-Amphetamine maintained high rates of drug-seeking behavior on the second-order schedule. D-Deprenyl maintained high rates of drug-seeking behavior similar to D-amphetamine. L-Deprenyl maintained lower rates of responding that were not significantly above saline substitution levels. Pretreatment with L-deprenyl failed to alter drug-seeking behavior maintained by D-amphetamine. These results indicate that D-deprenyl, but not L-deprenyl, may have abuse potential. Under conditions where drug-seeking and drug-taking behaviors are actively maintained by D-amphetamine, L-deprenyl, at doses that specifically inhibit type B monoamine oxidase, may not be effective as a treatment. C1 Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. NIDA, Preclin Pharmacol Sect,Intramural Res Program, Behav Neurosci Res Branch, DHHS,NIH, Baltimore, MD 21224 USA. MegaPharma, Budapest, Hungary. RP Yasar, S (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, 5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM syasar@jhmi.edu RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 FU Intramural NIH HHS [Z99 DA999999] NR 50 TC 10 Z9 10 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2006 VL 183 IS 4 BP 413 EP 421 DI 10.1007/s00213-005-0200-7 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 990EF UT WOS:000233725300004 PM 16292593 ER PT J AU Devan, BD Bowker, JL Duffy, KB Bharati, IS Jimenez, M Sierra-Mercado, D Nelson, CM Spangler, EL Ingram, DK AF Devan, BD Bowker, JL Duffy, KB Bharati, IS Jimenez, M Sierra-Mercado, D Nelson, CM Spangler, EL Ingram, DK TI Phosphodiesterase inhibition by sildenafil citrate attenuates a maze learning impairment in rats induced by nitric oxide synthase inhibition SO PSYCHOPHARMACOLOGY LA English DT Article DE phosphodiesterase inhibition; nitric oxide; nitric oxide synthase; cyclic GMP; NMDA receptor activation; aging; animal model; neurodegenerative disease; learning and memory; cognitive performance ID 14-UNIT T-MAZE; OBJECT RECOGNITION MEMORY; LONG-TERM POTENTIATION; ACCELERATED MOUSE-BRAIN; COGNITIVE ENHANCEMENT; CYCLIC-GMP; L-NAME; CHOLINERGIC HYPOTHESIS; CEREBRAL-CORTEX; L-ARGININE AB Rationale: The nitric oxide (NO)-cyclic guanosine monophosphate ( cGMP) signal transduction pathway has been implicated in some forms of learning and memory. Recent findings suggest that inhibition of phosphodiesterase (PDE) enzymes that degrade cGMP may have memory-enhancing effects. Objectives: We examined whether treatment with sildenafil citrate, a PDE type 5 inhibitor, would attenuate a learning impairment induced by inhibition of NO synthase [60 mg/kg N-omega-nitro-L-arginine methyl ester (L-NAME), i.p.]. Methods: Rats were pre-trained in a one-way active avoidance of foot shock in a straight runway and, on the next day, received 15 training trials in a 14-unit T-maze, a task that has been shown to be sensitive to aging and impairment of central NO signaling systems. Combined treatments of L-NAME or saline and sildenafil (1.0, 1.5, 3.0, or 4.5 mg/ kg, i.p.) or vehicle were given 30 and 15 min before training, respectively. Behavioral measures of performance included entries into incorrect maze sections ( errors), run time from start to goal ( latency), shock frequency, and shock duration. Results: Statistical analysis revealed that L-NAME impaired maze performance and that sildenafil ( 1.5 mg/ kg) significantly attenuated this impairment. Control experiments revealed that administration of L-NAME alone did not significantly increase latencies in a one-way active avoidance test and that different doses of sildenafil alone did not significantly alter complex maze performance. Conclusions: The results indicate that sildenafil may improve learning by modulating NO-cGMP signal transduction, a pathway implicated in age-related cognitive decline and neurodegenerative disease. C1 NIA, Behav Neurosci Sect, Lab Expt Gerontol, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Devan, BD (reprint author), NIA, Behav Neurosci Sect, Lab Expt Gerontol, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM DevanBr@grc.nia.nih.gov FU NIGMS NIH HHS [NIGMS 07717, NIGMS 08253] NR 50 TC 47 Z9 49 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2006 VL 183 IS 4 BP 439 EP 445 DI 10.1007/s00213-005-0232-z PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 990EF UT WOS:000233725300007 PM 16320087 ER PT J AU Aikins, DE Lissek, S AF Aikins, Deane E. Lissek, Shmuel TI Clinical applications of conditioned fear: Developmental risk, idiographic reactivity, and stress resilience SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res C1 Yale Univ, New Haven, CT 06520 USA. NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S11 EP S11 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400043 ER PT J AU Birbaumer, N Weber, C Buch, E Braun, C Cohen, L AF Birbaumer, Niels Weber, Cornelia Buch, Ethan Braun, Christoph Cohen, Leonardo TI Brain computer interface and restoration of movement in chronic stroke SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE brain computer interface; rehabilitation; MEG C1 NIH, Bethesda, MD USA. Univ Tubingen, D-72074 Tubingen, Germany. RI Braun, Christoph/E-4561-2010; Buch, Ethan/G-1981-2011; Braun, Christoph/J-4160-2014 OI Braun, Christoph/0000-0002-7836-4010; Braun, Christoph/0000-0002-7836-4010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S24 EP S24 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400107 ER PT J AU Birbaumer, N Sitaram, R AF Birbaumer, Niels Sitaram, Ranganatha TI BCI-regulation of neuronal substrates of emotions SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE brain computer interface; emotion C1 Univ Tubingen, D-72074 Tubingen, Germany. NIH, Bethesda, MD 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S23 EP S24 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400106 ER PT J AU Doerfel, D Werner, A von Kummer, R Schaefer, M Karl, A AF Doerfel, Denise Werner, Annett von Kummer, Ruediger Schaefer, Michael Karl, Anke TI Functional networks in episodic memory retrieval SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE functional neuroimaging; episodic memory C1 Dresden Univ Technol, Dresden, Germany. Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. Univ Southampton, Southampton SO9 5NH, Hants, England. 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 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S35 EP S35 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400159 ER PT J AU Finger, EC Marsh, AA Mitchell, DGV Sims, C Reid, M Pine, DS Blair, J AF Finger, Elizabeth C. Marsh, Abigail A. Mitchell, Derek G. V. Sims, Courtney Reid, Maggie Pine, Daniel S. Blair, James TI Prefrontal and amygdala abnormalities during decision making in children with psychopathic tendencies SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res C1 NIMH, Bethesda, MD USA. RI Finger, Elizabeth/B-6453-2015 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S18 EP S18 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400079 ER PT J AU Lissek, S Levenson, J Mcdowell, DJ Johnson, LL Levine, J Pine, DS Grillon, C AF Lissek, Shmuel Levenson, Jessica Mcdowell, Dana J. Johnson, Linda L. Levine, Jessica Pine, Daniel S. Grillon, Christian TI Using socially relevant unconditioned stimuli to examine the associative learning components of social anxiety disorder SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res C1 NIMH, Bethesda, MD USA. RI Lissek, Shmuel/B-6577-2008; Levenson, Jessica/O-5448-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S11 EP S11 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400045 ER PT J AU Nielsen, L AF Nielsen, Lis TI Emerging perspectives in the social and affective neuroscience of aging SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S4 EP S4 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400007 ER PT J AU Ruiz-Padial, E Sollers, JJ Costa, PT Thayer, JF AF Ruiz-Padial, Elisabeth Sollers, John J., III Costa, Paul T., Jr. Thayer, Julian F. TI Heart rate variability and personality: Physiological concomitants of the resilient personality? SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE personality; HRV; resilient C1 Univ Jaen, Jaen, Spain. Ohio State Univ, Columbus, OH 43210 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S83 EP S83 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400381 ER PT J AU Thayer, JF Christie, I West, A Sterling, C Abernethy, D Cizza, G Deak, A Phillips, T Heerwagen, J Kampschroer, K Soller, JJ Sternberg, EM AF Thayer, Julian F. Christie, Israel West, Anthony Sterling, Carolyn Abernethy, Darrell Cizza, Giovanni Deak, Andrea Phillips, Terry Heerwagen, Judith Kampschroer, Kevin Soller, John J. Sternberg, Esther M. TI The effects of the physical work environment on circadian variations in heart rate variability SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 24-29, 2006 CL Vancouver, CANADA SP Soc Psychophysiol Res DE heart rate variability; circadian variation; work C1 Ohio State Univ, Columbus, OH 43210 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2006 VL 43 SU 1 BP S97 EP S98 PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 076NQ UT WOS:000239965400448 ER PT J AU Stang, PE Brandenburg, NA Lane, MC Merikangas, KR Von Korff, MR Kessler, RC AF Stang, PE Brandenburg, NA Lane, MC Merikangas, KR Von Korff, MR Kessler, RC TI Mental and physical comorbid conditions and days in role among persons with arthritis SO PSYCHOSOMATIC MEDICINE LA English DT Article DE chronic pain; arthritis; mental disorders; chronic disease; disability; prevalence ID WORLD-HEALTH-ORGANIZATION; QUALITY-OF-LIFE; INTERNATIONAL DIAGNOSTIC INTERVIEW; PERFORMANCE QUESTIONNAIRE HPQ; FACTOR SURVEILLANCE SYSTEM; CHRONIC MEDICAL CONDITIONS; REPLICATION NCS-R; RHEUMATOID-ARTHRITIS; UNITED-STATES; CHRONIC PAIN AB Objective: To estimate the prevalence of comorbidity among people with arthritis in the US adult population and to determine the role of comorbidity in accounting for the association of arthritis with days out of role (a measure of inability to work or carry out normal activities). Methods: Data come from the National Comorbidity Survey Replication (NCS-R), a nationally representative household survey of 9,282 respondents ages 18 and older carried Out in 2001 to 2003. Arthritis was assessed by self-report in a chronic-conditions checklist, along with a wide range of other physical conditions. Mental and substance use disorders were ascertained with the World Health Organization Composite International Diagnostic Interview (CIDI). Number of days out of role was assessed for the 30 days before the interview. Results: Arthritis was reported by 27.3% of respondents, 80.9% of whom also reported at least one other physical or mental disorder, including 45.6% with another chronic pain condition, 62.3% with another chronic physical condition, and 24.3% with a 12-month mental disorder. Arthritis was significantly associated with days out of role, but comorbidity explained more than half of this association. No significant interactions were found between arthritis and the other conditions in predicting days out of role. Conclusion: Comorbidity is the rule rather than the exception among people with arthritis. Comorbidity accounts for most of the days out of role associated with arthritis. The societal burden of arthritis needs to be understood and managed within the context of these comorbid conditions. C1 W Chester Univ, Dept Hlth, W Chester, PA 19380 USA. Galt Associates, W Chester, PA USA. Pfizer Inc, New York, NY USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. NIMH, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. RP Stang, PE (reprint author), 1744 DeKalb Pike,175, Blue Bell, PA 19422 USA. EM pstang@galt-assoc.com FU FIC NIH HHS [R01-TW006481]; NIA NIH HHS [K08 AG022232, R01-AG022232]; NIDA NIH HHS [R01 DA016558]; NIMH NIH HHS [R01 MH069864, R01-MH069864, R13 MH066849, R13-MH066849, U01 MH060220, U01-MH60220, U13 MH066849] NR 67 TC 66 Z9 67 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2006 VL 68 IS 1 BP 152 EP 158 DI 10.1097/01.psy.0000195821.25811.b4 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 006ZL UT WOS:000234936500023 PM 16449426 ER PT S AU Das, R Bhattacharyya, R Kumar, A AF Das, Ranabir Bhattacharyya, Rangeet Kumar, Anil BE Goswami, D TI Investigation of a dipolar coupled 8-qubit system for quantum information processing by NMR SO Quantum Computing: Back Action 2006 SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 1st International Conference on Quantum Computing - Back Action CY MAR 06-12, 2006 CL Indian Inst Technol, Kanpur, INDIA HO Indian Inst Technol DE NMR quantum computing ID NUCLEAR-MAGNETIC-RESONANCE; SPECTROSCOPY; COMPUTATION; STATES; GATES; SPINS AB Dipolar couplings among spin-1/2 nuclei are long-range and have the potential to yield large mutually-coupled spin-systems for quantum information processing. An eight spin dipolar coupled system is investigated for building quantum processors. Transitions between various states are identified and complete energy-level diagram of the system is constructed with the help of a HET-Z-COSY spectrum. Transition selective pulses have been used to implement various controlled operations. Preparation of pseudopure states and implementation of controlled-NOT and controlled-SWAP gates are demonstrated. C1 NCI, Struct Biophys Lab, Frederick, MD 21702 USA. RP Das, R (reprint author), NCI, Struct Biophys Lab, Frederick, MD 21702 USA. NR 22 TC 0 Z9 0 U1 2 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0362-8 J9 AIP CONF PROC PY 2006 VL 864 BP 313 EP 323 PG 11 WC Computer Science, Theory & Methods; Physics, Applied SC Computer Science; Physics GA BFQ44 UT WOS:000243789900029 ER PT J AU Anders, JC Grigsby, PW Singh, AK AF Anders, Jon C. Grigsby, Perry W. Singh, Anurag K. TI Cisplatin chemotherapy (without erythropoietin) and risk of life-threatening thromboembolic events in carcinoma of the uterine cervix: the tip of the iceberg? A review of the literature SO RADIATION ONCOLOGY LA English DT Review AB Background: The risk of severe cardiovascular toxicity, specifically thromboembolic events (TE), in patients with cervical cancer receiving concurrent irradiation and cisplatin chemotherapy is reported to be less than 1% in several large prospective trials. However, the anecdotal risk appears to be far higher. Results and discussion: A review of several prospective trials demonstrates no treatment related grade 4 cardiovascular toxicities and only two grade 5 toxicities in 1424 (0.1%) collective patients. A recent publication and our own unpublished experience finds 6 of 128 (4.7%) patients developed grade 4 to 5 cardiovascular (thrombosis/embolism) toxicity. The differenc in incidence of severe or life threatening cardiovascular toxicity of 0.1 versus 4.7% is highly statistically significant (p < 0.00001.) Conclusion: This dramatic difference in incidence of cardiovascular toxicity raises the possibility that cardiovascular toxicities were inadequately reported on the listed prospective trials. For those patients enrolled in prospective trials, we suggest that thromboses should be diligently documented and reported. Only after the true incidence of thromboses is established can we implement appropriate levels of early screening and intervention that may prevent life threatening complications. C1 [Singh, Anurag K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Anders, Jon C.] Radiat Oncol Associates, Albuquerque, NM 87109 USA. [Grigsby, Perry W.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM andersj11@hotmail.com; pgrigsby@radonc.wustl.edu; singan@mail.nih.gov NR 21 TC 20 Z9 21 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PY 2006 VL 1 AR 14 DI 10.1186/1748-717X-1-14 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V66GX UT WOS:000204479500014 PM 16722547 ER PT J AU Belka, C Camphausen, KA AF Belka, Claus Camphausen, Kevin A. TI Why "Radiation Oncology" SO RADIATION ONCOLOGY LA English DT Editorial Material AB Radiotherapy continues to be a major treatment for solid tumours and is a cornerstone of modern oncology. The term 'radiation oncology' describes the integration of radiation therapy into the complexity of multi-modal therapy. Over the last ten years the crucial role of radiation therapy as part of multi-modality protocols in cancer care has been documented in numerous Phase III trials. Advances in treatment technology as well as the underlying biology of tumour resistance mechanisms will further strengthen the role of radiation oncology. The scientific role of radiation oncology is reflected by the increase in the number of papers related to radiation oncology in resources like Medline. In order to reflect the growing scientific importance of radiation oncology, radiation physics and radiation biology, we have initiated Radiation Oncology as the first open access journal in the field. Open access allows for a rapid and transparent publication process together with an unequalled opportunity to reach the widest reader spectrum possible. C1 [Belka, Claus] Univ Tubingen, Dept Radiat Oncol, D-72074 Tubingen, Germany. [Camphausen, Kevin A.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Belka, C (reprint author), Univ Tubingen, Dept Radiat Oncol, D-72074 Tubingen, Germany. EM claus.belka@uni-tuebingen.de; camphauk@mail.nih.gov NR 8 TC 4 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PY 2006 VL 1 AR 1 DI 10.1186/1748-717X-1-1 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V66GX UT WOS:000204479500001 PM 16722574 ER PT J AU Chan, LW Hapdey, S English, S Seidel, J Carson, J Sowers, AL Krishna, MC Green, MV Mitchell, JB Bacharach, SL AF Chan, Linda W. Hapdey, Sebastien English, Sean Seidel, Jurgen Carson, Joann Sowers, Anastasia L. Krishna, Murali C. Green, Michael V. Mitchell, James B. Bacharach, Stephen L. TI The influence of tumor oxygenation on F-18-FDG (fluorine-18 deoxyglucose) uptake: A mouse study using positron emission tomography (PET) SO RADIATION ONCOLOGY LA English DT Article AB Background: This study investigated whether changing a tumor's oxygenation would alter tumor metabolism, and thus uptake of F-18-FDG (fluorine-18 deoxyglucose), a marker for glucose metabolism using positron emission tomography (PET). Results: Tumor-bearing mice (squamous cell carcinoma) maintained at 37 degrees C were studied while breathing either normal air or carbogen (95% O-2, 5% CO2), known to significantly oxygenate tumors. Tumor activity was measured within an automatically determined volume of interest (VOI). Activity was corrected for the arterial input function as estimated from image and blood-derived data. Tumor FDG uptake was initially evaluated for tumor-bearing animals breathing only air (2 animals) or only carbogen (2 animals). Subsequently, 5 animals were studied using two sequential F-18-FDG injections administered to the same tumor-bearing mouse, 60 min apart; the first injection on one gas (air or carbogen) and the second on the other gas. When examining the entire tumor VOI, there was no significant difference of F-18-FDG uptake between mice breathing either air or carbogen (i.e. air/carbogen ratio near unity). However, when only the highest F-18-FDG uptake regions of the tumor were considered (small VOIs), there was a modest (21%), but significant increase in the air/carbogen ratio suggesting that in these potentially most hypoxic regions of the tumor, F-18-FDG uptake and hence glucose metabolism, may be reduced by increasing tumor oxygenation. Conclusion: Tumor F-18-FDG uptake may be reduced by increases in tumor oxygenation and thus may provide a means to further enhance F-18-FDG functional imaging. C1 [English, Sean; Sowers, Anastasia L.; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chan, Linda W.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hapdey, Sebastien; Seidel, Jurgen; Carson, Joann; Green, Michael V.; Bacharach, Stephen L.] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM lchan136@yahoo.com; Sebastien.Hapdey@rouen.fnclcc.fr; englishs@mail.nih.gov; jurgen_seidel@verizon.net; jcarson@cc.nih.gov; stasia@box-s.nih.gov; murali@helix.nih.gov; greengang@pop.mail.rcn.net; jbm@helix.nih.gov; steve.bacharach@radiology.ucsf.edu FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 33 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PY 2006 VL 1 AR 3 DI 10.1186/1748-717X-1-3 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V66GX UT WOS:000204479500003 PM 16722588 ER PT J AU Singh, AK Guion, P Susil, RC Citrin, DE Ning, H Miller, RW Ullman, K Smith, S Crouse, NS Godette, DJ Stall, BR Coleman, CN Camphausen, K Menard, C AF Singh, Anurag K. Guion, Peter Susil, Robert C. Citrin, Deborah E. Ning, Holly Miller, Robert W. Ullman, Karen Smith, Sharon Crouse, Nancy Sears Godette, Denise J. Stall, Bronwyn R. Coleman, C. Norman Camphausen, Kevin Menard, Cynthia TI Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided high dose rate brachytherapy boost SO RADIATION ONCOLOGY LA English DT Article AB Purpose: To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. Materials and methods: Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. Results: Median follow-up was 24 months (range 18-36 mo). During follow- up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. Conclusion: We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive. C1 [Singh, Anurag K.; Guion, Peter; Susil, Robert C.; Citrin, Deborah E.; Ning, Holly; Miller, Robert W.; Ullman, Karen; Smith, Sharon; Crouse, Nancy Sears; Godette, Denise J.; Stall, Bronwyn R.; Coleman, C. Norman; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH DHHS, Bethesda, MD 20892 USA. [Menard, Cynthia] Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Radiat Med Program, Toronto, ON M5G 2M9, Canada. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, NIH DHHS, Bldg 10,CRC Rm B2-3561,9000 Rockville Pike, Bethesda, MD 20892 USA. EM singan@mail.nih.gov; guionp@mail.nih.gov; susil@jhu.edu; citrind@mail.nih.gov; hning@mail.nih.gov; rwmiller@mail.nih.gov; ullmank@mail.nih.gov; smiths@mail.nih.gov; ncrouse@mail.nih.gov; godetted@mail.nih.gov; stallb@mail.nih.gov; ccoleman@mail.nih.gov; camphauk@mail.nih.gov; cynthia.menard@rmp.uhn.on.ca FU NIH; National Cancer Institute; Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and in collaboration with Nucletron. NR 31 TC 6 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PY 2006 VL 1 AR 28 DI 10.1186/1748-717X-1-28 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V66GX UT WOS:000204479500028 PM 16914054 ER PT J AU Singh, AK Tierney, RM Low, DA Parikh, PJ Myerson, RJ Deasy, JO Wu, CS Pereira, GC Wahab, SH Mutic, MSS Grigsby, PW Hope, AJ AF Singh, Anurag K. Tierney, Ryan M. Low, Daniel A. Parikh, Parag J. Myerson, Robert J. Deasy, Joseph O. Wu, Catherine S. Pereira, Gisele C. Wahab, Sasha H. Mutic, Sasa M. S. Grigsby, Perry W. Hope, Andrew J. TI A prospective study of differences in duodenum compared to remaining small bowel motion between radiation treatments: Implications for radiation dose escalation in carcinoma of the pancreas SO RADIATION ONCOLOGY LA English DT Article AB Purpose: As a foundation for a dose escalation trial, we sought to characterize duodenal and non-duodenal small bowel organ motion between fractions of pancreatic radiation therapy. Patients and methods: Nine patients (4 women, 5 men) undergoing radiation therapy were enrolled in this prospective study. The patients had up to four weekly CT scans performed during their course of radiation therapy. Pancreas, duodenum and non-duodenal small bowel were then contoured for each CT scan. On the initial scan, a four-field plan was generated to fully cover the pancreas. This plan was registered to each subsequent CT scan. Dose-volume histogram (DVH) analyses were performed for the duodenum, non-duodenal small bowel, large bowel, and pancreas. Results: With significant individual variation, the volume of duodenum receiving at least 80% of the prescribed dose was consistently greater than the remaining small bowel. In the patient with the largest inter-fraction variation, the fractional volume of non-duodenal small bowel irradiated to at least the 80% isodose line ranged from 1% to 20%. In the patient with the largest inter-fraction variation, the fractional volume of duodenum irradiated to at least the 80% isodose line ranged from 30% to 100%. Conclusion: The volume of small bowel irradiated during four-field pancreatic radiation therapy changes substantially between fractions. This suggests dose escalation may be possible. However, dose limits to the duodenum should be stricter than for other segments of small bowel. C1 [Singh, Anurag K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Tierney, Ryan M.; Low, Daniel A.; Parikh, Parag J.; Myerson, Robert J.; Deasy, Joseph O.; Wu, Catherine S.; Pereira, Gisele C.; Wahab, Sasha H.; Mutic, Sasa M. S.; Grigsby, Perry W.; Hope, Andrew J.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. RP Singh, AK (reprint author), NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. EM singan@mail.nih.gov; rtierney@radonc.wustl.edu; low@radonc.wustl.edu; parikh@radonc.wustl.edu; myerson@radonc.wustl.edu; deasey@radonc.wustl.edu; cwu@radonc.wustl.edu; pereira@radonc.wustl.edu; wahab@radonc.wustl.edu; mutic@radonc.wustl.edu; grigsby@radonc.wustl.edu; ahope@radonc.wustl.edu OI Deasy, Joseph/0000-0002-9437-266X FU NIH; National Cancer Institute; Center for Cancer Research; [R01CA96679] FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and also in part by R01CA96679.; The authors wish to thank Angel Medina of Barnes-Jewish Hospital, Saint Louis, MO for making resources available to complete this study. NR 8 TC 11 Z9 13 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PY 2006 VL 1 AR 33 DI 10.1186/1748-717X-1-33 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V66GX UT WOS:000204479500033 PM 16952315 ER PT J AU Ullman, KL Ning, H Susil, RC Ayele, A Jocelyn, L Havelos, J Guion, P Xie, HC Li, G Arora, BC Cannon, A Miller, RW Coleman, CN Camphausen, K Menard, C AF Ullman, Karen L. Ning, Holly Susil, Robert C. Ayele, Asna Jocelyn, Lucresse Havelos, Jan Guion, Peter Xie, Huchen Li, Guang Arora, Barbara C. Cannon, Angela Miller, Robert W. Coleman, C. Norman Camphausen, Kevin Menard, Cynthia TI Intra- and inter-radiation therapist reproducibility of daily isocenter verification using prostatic fiducial markers SO RADIATION ONCOLOGY LA English DT Article ID PORTAL IMAGING DEVICE; CONFORMAL RADIOTHERAPY; RADIOPAQUE MARKERS; LOCALIZATION; MOTION; CANCER; CARCINOMA; ERRORS AB Background: We sought to determine the intra- and inter-radiation therapist reproducibility of a previously established matching technique for daily verification and correction of isocenter position relative to intraprostatic fiducial markers (FM). Materials and methods: With the patient in the treatment position, anterior-posterior and left lateral electronic images are acquired on an amorphous silicon flat panel electronic portal imaging device. After each portal image is acquired, the therapist manually translates and aligns the fiducial markers in the image to the marker contours on the digitally reconstructed radiograph. The distances between the planned and actual isocenter location is displayed. In order to determine the reproducibility of this technique, four therapists repeated and recorded this operation two separate times on 20 previously acquired portal image datasets from two patients. The data were analyzed to obtain the mean variability in the distances measured between and within observers. Results: The mean and median intra- observer variability ranged from 0.4 to 0.7 mm and 0.3 to 0.6 mm respectively with a standard deviation of 0.4 to 1.0 mm. Inter-observer results were similar with a mean variability of 0.9 mm, a median of 0.6 mm, and a standard deviation of 0.7 mm. When using a 5 mm threshold, only 0.5% of treatments will undergo a table shift due to intra or interobserver error, increasing to an error rate of 2.4% if this threshold were reduced to 3 mm. Conclusion: We have found high reproducibility with a previously established method for daily verification and correction of isocenter position relative to prostatic fiducial markers using electronic portal imaging. C1 [Ullman, Karen L.; Ning, Holly; Ayele, Asna; Jocelyn, Lucresse; Havelos, Jan; Guion, Peter; Xie, Huchen; Li, Guang; Arora, Barbara C.; Cannon, Angela; Miller, Robert W.; Coleman, C. Norman; Camphausen, Kevin; Menard, Cynthia] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. [Susil, Robert C.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Menard, Cynthia] Univ Toronto, Princess Margaret Hosp, Radiat Med Program, Toronto, ON M4X 1C3, Canada. RP Ullman, KL (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH,DHHS, Bldg 10,CRC Rm B2 SW 3500,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ullmank@mail.nih.gov; ningh@mail.nih.gov; rcs@jhu.edu; ayelea@mail.nih.gov; ljocelyn@mrccnet.com; havelosj@mail.nih.gov; guionp@mail.nih.gov; xieh@mail.nih.gov; lig@mail.nih.gov; arorab@mail.nih.gov; cannona@mail.nih.gov; millerrw@mail.nih.gov; colemanc@mail.nih.gov; camphauk@mail.nih.gov; cynthia.menard@rmp.uhn.on.ca NR 19 TC 10 Z9 10 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-717X J9 RADIAT ONCOL JI Radiat. Oncol. PY 2006 VL 1 AR 2 DI 10.1186/1748-717X-1-2 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA V66GX UT WOS:000204479500002 PM 16722575 ER PT J AU Drozdovitch, V Germenchuk, M Bouville, A AF Drozdovitch, V. Germenchuk, M. Bouville, A. TI Using total beta-activity measurements in milk to derive thyroid doses from Chernobyl fallout SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID ACCIDENT; BYELARUS; CANCER; RECONSTRUCTION; EXPOSURE AB Following the Chernobyl accident, more than 200 childhood thyroid cancer cases have been observed in Brest Oblast of Belarus in territories slightly contaminated with Cs-137, but with suspected relatively high I-131 fallout. The most helpful measurements available that can be used to estimate thyroid doses for the population of Brest Oblast are the total beta-activity measurements in cow's milk performed using DP-100 device within a few weeks after the accident. The I-131 concentrations in milk were derived from the total beta-activity measurements on the basis of (1) a radioecological model used to estimate the variation with time of the radionuclide composition in milk and (2) the determination of the calibration factors of the DP-100 device for the most important radionuclides present in milk. As a result, I-131 concentrations in milk were reconstructed for territories with different levels of Cs-137 deposition. A non-linear dependence of the I-131 concentration in milk on the Cs-137 deposition density was obtained; it was used to estimate the thyroid doses from the consumption of I-131-contaminated cow's milk by the population of Brest Oblast. The average individual thyroid doses have been estimated to be 0.15, 0.18, 0.12, 0.06, 0.04 and 0.03 Gy for newborn, children aged 1, 5, 10 and 15 y and adults, respectively. The collective thyroid dose for the entire population of Brest Oblast is estimated to be 64,500 man Gy, the contribution from the adult population being about one half of the total. The methodology that is described could be applied in the framework of epidemiological studies of the relationship between radiation exposure to the thyroid gland and thyroid cancer in areas where numerous total beta-activity measurements in cow's milk were performed within a few weeks after the accident. C1 Int Agcy Res Canc, F-69372 Lyon 08, France. SOSNY, Joint Inst Power & Nucl Res, Minsk 220109, Byelarus. Ctr Radiat Control & Monitoring Environm, Minsk 220645, Byelarus. NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Drozdovitch, V (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM drozdovitch@iarc.fr NR 20 TC 4 Z9 4 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2006 VL 118 IS 4 BP 402 EP 411 DI 10.1093/rpd/nci360 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 072EQ UT WOS:000239656300007 PM 16436522 ER PT B AU Drake, JW AF Drake, John W. BE Cigna, AA Druante, M TI Mutation and DNA repair: From the green pamphlet to 2005 SO Radiation Risk Estimates in Normal and Emergency Situations SE NATO SECURITY THROUGH SCIENCE SERIES B: PHYSICS AND BIOPHYSICS LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Impact of Radiation Risk Estimates in Normal and Emergency Situations CY SEP 08-11, 2005 CL Yerevan, ARMENIA SP NATO DE DNA repair; replication repair; templated mutations; multiple mutations ID REPLICATION REPAIR; BACTERIOPHAGE-T4; DAMAGE; MODEL AB The early conceptual basis of gene structure and mutation were laid down in a handful of seminal papers, one of the best remembered being the "Green Pamphlet" of 1935 by N.V. Timofeeff-Ressovsky, K.G. Zimmer and M. Delbruck entitled "On the Nature of Gene Mutation and Gene Structure". The concepts of a molecular basis for the gene and its mutability have expanded hugely since then and have generated the entire field of DNA repair. Here, two current insights into DNA repair and mutation are displayed. Replication repair is a newly established mode of recombination repair that works through a copy-choice (templateswitching) mechanism and that has been reconstructed in vitro using the enzymes of DNA replication elaborated by bacteriophage T4. In contrast, a pathological mode of primer-strand switching generates templated complex mutations, and these greatly increase in frequency when the shepherding proteins of replication repair are disabled. At the same time, many spectra are found to contain a different kind of complex mutation whose components are more widely scattered. These are argued to arise mostly through transient bouts of hypermutation and are likely to contribute to carcinogenesis and to the virulence of microbial pathogens. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 12 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-4954-5 J9 NATO SEC SCI B PHYS PY 2006 VL 9 BP 271 EP 281 DI 10.1007/1-4020-4956-0_27 PG 11 WC Nuclear Science & Technology SC Nuclear Science & Technology GA BFQ47 UT WOS:000243842200027 ER PT B AU Liu, A Wu, CQ Yu, KF AF Liu, Aiyi Wu, Chengqing Yu, Kai F. BE Hsiung, AC Ying, Z Zhang, CH TI Incorporating overrunning data into the analysis of both primary and secondary endpoints in a sequential trial SO Random Walk, Sequential Analysis and Related Topics: A FESTSCHRIFT IN HONOR OF YUAN-SHIH CHOW LA English DT Proceedings Paper CT Festschrift in Honor of Yuan Shih Chow on Random Walk, Sequential Analysis and Related Topics CY JUL 18-19, 2004 CL Fudan Univ, Shanghai, PEOPLES R CHINA HO Fudan Univ DE additional data; arm-specific analysis; clinical trials; interim analysis; patients allocation; secondary endpoints; stopping boundaries ID CLINICAL-TRIALS AB We propose methods for incorporating overrunning data, either balanced or unbalanced, into the final analysis of a sequential clinical trial comparing an experimental arm with a control arm. We consider inference on the primary endpoint for which the sequential test is designed and a correlated secondary endpoint. By separating the monitoring process into arm-specific processes, we derive the sufficient statistics and show how the independent overrunning data can be combined with the trial data at stopping and thus allow the likelihood-based inference to be conducted. C1 NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Rockville, MD USA. RP Liu, A (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD USA. OI Liu, Aiyi/0000-0002-6618-5082 NR 11 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-270-355-2 PY 2006 BP 56 EP 68 DI 10.1142/9789812772558_0004 PG 13 WC Statistics & Probability SC Mathematics GA BFY59 UT WOS:000245458600005 ER PT J AU Levine, RL AF Levine, RL TI Fixation of nitrogen in an electrospray mass spectrometer SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID DENSITY-FUNCTIONAL CALCULATIONS; ABLATED IRON ATOMS; INFRARED-SPECTRA; LIQUID-CHROMATOGRAPHY; TRIFLUOROACETIC-ACID; MOLECULES; SYSTEM; FE AB The formation of an iron-nitrogen compound in an electrospray ionization instrument is reported. The iron was released from the stainless steel electrospray needle by acetic acid added to displace trifluoroacetic acid and the nitrogen was present as the drying gas. The product is an iron nitride ion, [N2FeOH](1+), m/z 100.9438, and is capable of addition to peptides and proteins. Published in 2006 by John Wiley & Sons, Ltd. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 FU Intramural NIH HHS NR 11 TC 5 Z9 5 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 2006 VL 20 IS 12 BP 1828 EP 1830 DI 10.1002/rcm.2519 PG 3 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 053VE UT WOS:000238333000002 PM 16705654 ER PT J AU Gardner, ER Liau, CT Chu, ZTE Figg, WD Sparreboom, A AF Gardner, Erin R. Liau, Chi-Ting Chu, Zyting E. Figg, William D. Sparreboom, Alex TI Determination of paclitaxel in human plasma following the administration of Genaxol or Genetaxyl by liquid chromatography/tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SOLID-PHASE EXTRACTION; QUANTITATIVE-DETERMINATION; SENSITIVE ASSAY; MOUSE PLASMA; QUANTIFICATION; PERFORMANCE; METABOLITES; VALIDATION; DOCETAXEL; TISSUE AB A sensitive and specific assay for paclitaxel in plasma has been developed to overcome limitations in previously published assays, using liquid chromatography with tandem mass spectrometric detection. Plasma samples (100 mu L) were subjected to liquid-liquid extraction with 1-chlorobutane/acetonitrile (4:1, v/v), with [H-2(5)]paclitaxel employed as the internal standard. Chromatography was carried out with a Waters SymmetryShield C8 column (50 X 2.1 mm, 3.5 mu m). The total run time, including equilibration, was 8 min, using a gradient of acetonitrile and 10 mM ammonium formate, pH 4.0. The assay is accurate and precise over the range of 2-2500 ng/mL and has been successfully applied to study the clinical pharmacokinetics of two formulations of paclitaxel, Genaxol and Genetaxyl, given orally and intravenously. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NCI, Clin Pharmacol Res Core, Canc Res Ctr, Bethesda, MD 20892 USA. SAIC Frederick Inc, Clin Pharmacol Res Core, NCI Frederick, Frederick, MD 21702 USA. Chang Gung Mem Hosp, Taipei, Taiwan. Genovate Biotechnol, Taipei, Taiwan. RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Canc Res Ctr, 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 FU Intramural NIH HHS [, NIH0011335962]; NCI NIH HHS [N01-CO-12400]; PHS HHS [NIH0011335962] NR 17 TC 9 Z9 11 U1 0 U2 3 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 2006 VL 20 IS 14 BP 2170 EP 2174 DI 10.1002/rcm.2577 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 063YB UT WOS:000239054700015 PM 16779869 ER PT J AU Simons, BL Wang, GH Shen, RF Knepper, MA AF Simons, Brigitte L. Wang, Guanghui Shen, Rong-Fong Knepper, Mark A. TI In vacuo isotope coded alkylation technique (IVICAT); an N-terminal stable isotopic label for quantitative liquid chromatography/mass spectrometry proteomics SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID DESORPTION/IONIZATION MASS-SPECTROMETRY; MEDULLARY COLLECTING DUCT; COMPLEX PROTEIN MIXTURES; AFFINITY TAGS; GEL-ELECTROPHORESIS; CONTAINING PEPTIDES; MOUSE PITUITARY; ION; IDENTIFICATION; ABUNDANCE AB We present a new isotopic labeling strategy to modify the N-terminal amino group of peptides in a quantifiable reaction without the use of expensive reagents or solvents. The In Vacuo Isotope Coded Alkylation Technique (IVICAT) is a methylation reaction, carried out at low pressure (< 100 mTorr), that results in a stable quaternary trimethylammonium group, thus adding a permanent positive charge at the N-terminus of peptides without modifying the e-amino groups of lysine. The methylation reaction increases the signal intensity of modified peptides in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and liquid chromatography (LC)/MS and the isotopic peak pair differs by 9 mass units which can be easily resolved by either instrument. N-terminally trimethylated peptides exhibit collision-induced dissociation (CID) mass spectra that differ from their unmodified analogues by an enhanced b-ion series in MS2 spectra due to the fixed positive charge. Using LC/MS/MS with an LTQ mass analyzer for quantification, the experimentally determined ratios of H-9- to D-9-trimethyl-labeled peptides of beta-casein provided accurate estimates of the actual ratios with low % error. IVICAT labeling also accurately quantified proteins in rat kidney inner medullary collecting duct cell types, as judged by comparison with relative quantification by subsequent immunoblotting experiments. IVICAT labeling, when used in conjunction with the new proteomics software QUIL, can accurately report relative protein abundances and increase the sequence coverage of proteins of tissue proteomes. Published in 2006 by John Wiley & Sons, Ltd. C1 NIH, Bethesda, MD 20892 USA. NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. NHLBI, Proteom Core Facil, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NIH, Bldg 10,Room 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL001285] NR 46 TC 16 Z9 19 U1 1 U2 4 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 2006 VL 20 IS 16 BP 2463 EP 2477 DI 10.1002/rcm.2615 PG 15 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 075ZJ UT WOS:000239926400013 PM 16862635 ER PT J AU Goodwin, MB Boshoff, HI Barry, CE Dowd, CS AF Goodwin, Michael B. Boshoff, Helena I. Barry, Clifton E. Dowd, Cynthia S. TI Quantification of small molecule organic acids from Mycobacterium tuberculosis culture supernatant using ion exclusion liquid chromatography/mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID CARBOXYLIC-ACIDS; MASS-SPECTROMETRY; SEPARATION; CHEESE; SUGARS; FRUIT AB Quantitative analysis of cellular small molecule organic acids of intermediary metabolism can provide critical insight into bacterial metabolic pathways. The concentration of these metabolites in culture supernatant varies at different growth stages or under particular environmental conditions reflecting both the energy and the biosynthetic needs, yielding metabolic information about the microorganism. The method described here utilizes ion exclusion chromatography with formic acid, coupled with a mass-selective detector using selective ion monitoring with negative mode electrospray ionization (SIM ES-), to detect and quantify several small organic acids in culture supernatants. The mu M limits of quantitation (LOQs) were found to be 5.5 +/- 0.9 for pyruvate, 7.0 +/- 0.4 for malate, 2.5 +/- 0.5 for succinate, 12.7 +/- 0.8 for lactate, and 6.6 +/- 0.2 for fumarate. The method was used to detect and quantify these acids in the culture supernatants from Mycobacterium tuberculosis. Supernatant samples were spiked with stable-isotope-labeled internal standards, and the organic acids were quantified by isotope ratiometry. Published in 2006 by John Wiley & Sons, Ltd. C1 NIAID, TB Res Sect, Lab Immunogenet, Rockville, MD 20852 USA. RP Dowd, CS (reprint author), 12441 Parklawn Dr,Twinbrook 2,Room 235, Rockville, MD 20852 USA. EM cdowd@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 12 TC 5 Z9 5 U1 0 U2 3 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 2006 VL 20 IS 22 BP 3345 EP 3350 DI 10.1002/rcm.2745 PG 6 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 107KD UT WOS:000242168900012 PM 17044117 ER PT S AU Ritt, DA Daar, IO Morrison, DK AF Ritt, Daniel A. Daar, Ira O. Morrison, Deborah K. BE Balch, WE Der, CJ Hall, A TI KSR regulation of the Raf-MEK-ERK cascade SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID KINASE SUPPRESSOR; SIGNAL-TRANSDUCTION; MAP KINASE; SCAFFOLD PROTEINS; 14-3-3 BINDING; GENE ENCODES; C-ELEGANS; SITES; PHOSPHORYLATION; IDENTIFICATION AB Kinase suppressor of Ras (KSR) is a conserved component of the Ras pathway that functions as a molecular scaffold to enhance signaling between the core kinase components of the ERK cascade-Raf, MEK, and ERK. KSR interacts constitutively with MEK and translocates from the cytosol to the plasma membrane on Ras activation. At the membrane, KSR coordinates the assembly of a multiprotein complex containing Raf, MEK, and ERK and facilitates signal transmission from Raf to MEK and ERK. In this chapter, we will describe methods for assessing KSR function in response to Ras pathway activation. Protocols will be included that examine the ERK scaffolding activity and subcellular localization of KSR. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Ritt, DA (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. OI Daar, Ira/0000-0003-2657-526X FU Intramural NIH HHS NR 27 TC 4 Z9 4 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 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 224 EP 237 DI 10.1016/S0076-6879(05)07019-9 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800019 PM 16757327 ER PT S AU Vos, MD Clark, GJ AF Vos, Michele D. Clark, Geoffrey J. BE Balch, WE Der, CJ Hall, A TI RASSF family proteins and Ras transformation SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID TUMOR-SUPPRESSOR GENE; HUMAN CANCERS; EFFECTOR; BINDING; NORE1; IDENTIFICATION; STABILITY; APOPTOSIS; CELLS AB There are six members of the RASSF gene family, with RASSF1 being the best characterized. All six genes produce proteins that contain Ras Association (RA) domains that can interact directly with activated Ras in overexpression studies. Their role in mediating the biological effects of Ras remains under investigation. However, they seem to modulate some of the growth inhibitory responses mediated by Ras. Moreover, evidence is accumulating that RASSF family members may serve as tumor suppressors that succumb to inactivation during the evolution of the transformed phenotype. Thus, RASSF proteins may be described as effector/tumor suppressors, in contrast to traditional Ras effectors such as Raf and PI-3 kinase, which may be considered to be effector/oncoproteins. C1 NCI, Dept Cell & Canc Biol, Rockville, MD USA. RP Vos, MD (reprint author), NCI, Dept Cell & Canc Biol, Rockville, MD USA. NR 26 TC 7 Z9 8 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 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 311 EP 322 DI 10.1016/S0076-6879(05)07026-0 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800026 PM 16757334 ER PT S AU Ward, Y Kelly, K AF Ward, Yvona Kelly, Kathleen BE Balch, WE Der, CJ Hall, A TI Gem protein signaling and regulation SO REGULATORS AND EFFECTORS OF SMALL GTPASES: RAS FAMILY SE Methods in Enzymology LA English DT Review; Book Chapter ID CALCIUM-CHANNEL ACTIVITY; GTP-BINDING; RAS FAMILY; RHO-KINASE; GTPASES; MEMBER; PHOSPHORYLATION; INTERACTS; REM; SUPERFAMILY AB Gem is a member of the RGK family of GTP-binding proteins within the Ras superfamily possessing a ras-like core and terminal extensions. We have used a variety of cell-based assays to investigate the physiological role of Gem and combined these assays with site-directed mutagenesis of Gem protein to identify the sites responsible for regulation of Gem activity. One function of Gem that has been explained is the inhibition of Rho kinase (ROK)-mediated cytoskeletal rearrangement. Transient expression of Gem in endothelial cells and stable transfection of fibroblasts resulted in decreased stress fiber formation and focal adhesion assembly. A neurite extension model using N1E-115 murine neuroblastoma showed that Gem inhibits actinomyosin-related contractility by specifically opposing ROK beta activity. Phospho-specific antibodies were used in Western blot analysis to show that Gem prevents phosphorylation of the regulatory subunit of myosin light chain and myosin phosphatase by ROK beta. On the contrary, LIMK, another substrate of ROK beta, was unaffected by Gem expression as demonstrated by an in vitro kinase assay, suggesting that Gem exerts its effect by changing the substrate specificity of ROK beta rather than by blocking its catalytic activity. Point mutations of Gem at serines 261 and 289 in the carboxyl-terminus inhibited Gem function, indicating that posttranslational phosphorylation of these serines regulates Gem's effect on cytoskeletal reorganization. Another biological role of Gem is inhibition of voltage-gated calcium channel activity. By use of a PC12 cell model combined with site-directed mutagenesis, we demonstrated that Gem inhibits growth hormone secretion stimulated by calcium influx through L-type calcium channels and that this function is dependent on GTP and calmodulin binding to Gem. The theory and method for the assays discussed previously are reviewed here. C1 NIH, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ward, Y (reprint author), NIH, Cell & Canc Biol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. NR 23 TC 6 Z9 6 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 0-12-182812-3 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 407 BP 468 EP 483 DI 10.1016/S0076-6879(05)07038-2 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEF32 UT WOS:000237082800038 PM 16757346 ER PT J AU Patton, JT Silvestri, LS Tortorici, MA Carpio, RVD Taraporewala, ZF AF Patton, J. T. Silvestri, L. S. Tortorici, M. A. Carpio, R. Vasquez-Del Taraporewala, Z. F. TI Rotavirus genome replication and morphogenesis: Role of the viroplasm SO REOVIRUSES: ENTRY, ASSEMBLY AND MORPHOGENESIS SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID DOUBLE-STRANDED-RNA; NONSTRUCTURAL PROTEIN NSP2; INFECTED-CELLS; MESSENGER-RNA; PHOSPHOPROTEIN NSP5; BINDING ACTIVITY; OPEN CORES; IN-VIVO; PHOSPHORYLATION; LOCALIZATION AB The rotaviruses, members of the family Reoviridae, are icosahedral triple-layered viruses with genomes consisting of 11 segments of double-stranded (ds)RNA. A characteristic feature of rotavirus-infected cells is the formation of large cytoplasmic inclusion bodies, termed viroplasms. These dynamic and highly organized structures serve as viral factories that direct the packaging and replication of the viral genome into early capsid assembly intermediates. Migration of the intermediates to the endoplasmic reticulum (ER) initiates a budding process that culminates in final capsid assembly. Recent information on the development and organization of viroplasms, the structure and function of its components, and interactive pathways linking RNA synthesis and capsid assembly provide new insight into how these micro environments serve to interface the replication and morphogenetic processes of the virus. C1 NIAID, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, Natl Inst Hlth, 50 S Dr,MSC 8026,Room 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 NR 68 TC 42 Z9 47 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 309 BP 169 EP 187 PG 19 WC Immunology; Microbiology SC Immunology; Microbiology GA BEY98 UT WOS:000240187200006 PM 16909900 ER PT S AU Raymont, V Grafman, J AF Raymont, Vanessa Grafman, Jordan BE Moller, AR TI Cognitive neural plasticity during learning and recovery from brain damage SO REPROGRAMMING THE BRAIN SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Reprogramming the Human Brain CY APR 07-08, 2005 CL Univ Texas Dallas, Richardson, TX HO Univ Texas Dallas DE neural plasticity; brain injury; learning; brain disorders; aging; cognitive ability ID POSITRON-EMISSION-TOMOGRAPHY; SOMATOSENSORY CORTEX; SENSORIMOTOR CORTEX; CORTICAL PLASTICITY; ADULT MONKEYS; INJURY; STROKE; REORGANIZATION; CHILDREN; NEUROGENESIS AB The process of neuroplasticity is the ability of the brain to change, either in response to experience or injury. It is a vital process both during normal development and for the recovery after brain injury. Recent research has emphasized that this takes place via both local restitution as well as reorganization and compensatory reassignment. The fact that the brain can undergo such plastic changes has provided evidence for what underlies developmental brain disorders, as well as the variable response to injury at different points in the lifespan. The factors affecting plasticity and its long-term consequences may have increasing importance in exposing the pattern of changes that occur in the normal brain with aging. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Vietnam Head Injury Study, Bethesda, MD USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov NR 56 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-51602-2 J9 PROG BRAIN RES PY 2006 VL 157 BP 199 EP 206 DI 10.1016/S0079-6123(06)57013-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA BGH62 UT WOS:000247002900013 PM 17046672 ER PT B AU Squibb, KS AF Squibb, Katherine S. BE Wagner, W Steinzor, R TI Basic Science at Risk: Protecting the Independence of Research SO RESCUING SCIENCE FROM POLITICS: REGULATION AND THE DISTORTION OF SCIENTIFIC RESEARCH LA English DT Article; Book Chapter ID FROGS; HERBICIDES; ATRAZINE C1 [Squibb, Katherine S.] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Squibb, Katherine S.] Univ Maryland, Syst Wide Grad Program Toxicol, Baltimore, MD 21201 USA. [Squibb, Katherine S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Squibb, Katherine S.] Univ Maryland, Sch Law, Environm Law Clin Risk Assessment & Publ Hlth Fie, Baltimore, MD 21201 USA. RP Squibb, KS (reprint author), Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-54009-4 PY 2006 BP 46 EP 60 DI 10.1017/CBO9780511751776.005 D2 10.2277/ 0521855209 PG 15 WC Law; Public Administration SC Government & Law; Public Administration GA BYI23 UT WOS:000298914400005 ER PT S AU Thoma, GR Mao, S Misra, D Rees, J AF Thoma, George R. Mao, Song Misra, Dharitri Rees, John BE Gonzalo, J Thanos, C Verdejo, MF Carrasco, RC TI Design of a digital library for early 20(th) century medico-legal documents SO RESEARCH AND ADVANCED TECHNOLOGY FOR DIGITAL LIBRARIES SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 10th European Conference on Research and Advanced Technology for Digital Libraries CY SEP 17-22, 2006 CL Alicante, SPAIN SP DELOS Network Excellence Digital Libraries, Grp Santander, Minist Educ & Ciencia, Patronato Municipal Turismo Alicante, Red Investigac Bibliotecas Digitales, Fdn Biblioteca Miguel Cervantes, Univ Alciante, Dept Lenguajes & Sistemas Informat, UNED AB The research value of important government documents to historians of medicine and law is enhanced by a digital library of such a collection being designed at the U.S. National Library of Medicine. This paper presents work toward the design of a system for preservation and access of this material, focusing mainly on the automated extraction of descriptive metadata needed for future access. Since manual entry of these metadata for thousands of documents is unaffordable, automation is required. Successful metadata extraction relies on accurate classification of key textlines in the document. Methods are described for the optimal scanning alternatives leading to high OCR conversion performance, and a combination of a Support Vector Machine (SVM) and Hidden Markov Model (HMM) for the classification of textlines and metadata extraction. Experimental results from our initial research toward an optimal textline classifier and metadata extractor are given. C1 US Natl Lib Med, Bethesda, MD 20894 USA. RP Thoma, GR (reprint author), US Natl Lib Med, Bethesda, MD 20894 USA. EM gthoma@mail.nih.gov; smao@mail.nih.gov; dmisra@mail.nih.gov; jrees@mail.nih.gov NR 4 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-44636-2 J9 LECT NOTES COMPUT SC PY 2006 VL 4172 BP 147 EP 157 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Information Science & Library Science SC Computer Science; Information Science & Library Science GA BFD07 UT WOS:000241101500013 ER PT S AU Przytycka, TM AF Przytycka, TM BE Apostolico, A Guerra, C Istrail, S Pevzner, P Waterman, M TI An important connection between network motifs and parsimony models SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 10th Annual International Conference on Research in Computational Molecular Biology CY APR 02-05, 2006 CL Venice, ITALY SP Univ Padova, Dept Informat Engn, MIT, Broad Inst, Havard, Broad Inst, Coll Comp Georgia Tech, US Dept Energy, IBM Corp, Int Soc Computat Biol, Italian Assoc Informat & Automat Computat, US Natl Sci Fdn ID SCALE-FREE; PHYLOGENETIC ANALYSIS; PROTEIN-INTERACTION AB We demonstrate an important connection between network motifs in certain biological networks and validity of evolutionary trees constructed using parsimony methods. Parsimony methods assume that taxa are described by a set of characters and infer phylogenetic trees by minimizing number of character changes required to explain observed character states. From the perspective of applicability of parsimony methods, it is important to assess whether the characters used to infer phylogeny are likely to provide a correct tree. We introduce a graph theoretical characterization that helps to select correct characters. Given a set of characters and a set of taxa, we construct a network called character overlap graph. We show that the character overlap graph for characters that are appropriate to use in parsimony methods is characterized by significant under-representation of subnetworks known as holes, and provide a mathematical validation for this observation. This characterization explains success in constructing evolutionary trees using parsimony method for some characters (e.g. protein domains) and lack of such success for other characters (e.g. introns). In the latter case, the understanding of mathematical obstacles to applying parsimony methods in a direct way has lead us to a new approach for dealing with inconsistent and/or noisy data. Namely, we introduce the concept of persistent characters which is similar but less restrictive than the well known concept of pairwise compatible characters. Application of this approach to introns produces the evolutionary tree consistent with the Coelomata hypothesis. In contrast, the direct application of a parsimony method, using introns as characters, produces a tree which is inconsistent with any of the two competing evolutionary hypotheses. Similarly, replacing persistence with pairwise compatibility does not lead to a correct tree. This indicates that the concept of persistence provides an important addition to the parsimony metohds. C1 NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20894 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20894 USA. EM przytyck@mail.nih.gov NR 34 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-33295-2 J9 LECT NOTES COMPUT SC PY 2006 VL 3909 BP 321 EP 335 PG 15 WC Biochemical Research Methods; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Biochemistry & Molecular Biology; Computer Science GA BEE73 UT WOS:000236991800027 ER PT J AU Engelhardt, JB Toseland, RW Gao, J Banks, S AF Engelhardt, JB Toseland, RW Gao, J Banks, S TI Long-term effects of outpatient geriatric evaluation and management on health care utilization, cost, and survival SO RESEARCH ON SOCIAL WORK PRACTICE LA English DT Article DE assessment; health economics; health care utilization ID RANDOMIZED CLINICAL-TRIAL; CHRONIC ILLNESS; EMERGENCY; GEM AB Purpose: The long-term effectiveness and efficiency of an outpatient geriatric evaluation and management (GEM) program was compared to usual primary care (UPC). Design and Method A randomized controlled group design was used. Health care utilization, cost of care, and survival were assessed during a 48-month period among a sample of 160 male veterans age 55 and over who were above-average users of outpatient services. Results: The results indicate that GEM patients incurred significantly lower overall health care costs than UPC patients by 24 months and that cost savings plateaued during the 24- to 48-month period. Cost savings were due primarily to fewer hospital days of care. No significant differences were found in survival. Implications: Results of this follow-up study suggest that outpatient GEM offers a specialized health delivery option for frail older persons that may reduce costs over the long term without having a negative impact on survival rates. C1 NIH, Bethesda, MD 20892 USA. RP Engelhardt, JB (reprint author), Ctr Adv Illness Care Coordinat, 113 Holland Ave (11T), Albany, NY 12208 USA. EM Jengelhart@aol.com NR 30 TC 5 Z9 5 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7315 J9 RES SOCIAL WORK PRAC JI Res. Soc. Work. Pract. PD JAN PY 2006 VL 16 IS 1 BP 20 EP 27 DI 10.1177/1049731505276047 PG 8 WC Social Work SC Social Work GA 993ER UT WOS:000233937900003 ER PT S AU Suomi, SJ AF Suomi, Stephen J. BE Lester, BM Masten, AS McEwen, B TI Risk, resilience, and gene x environment interactions in rhesus monkeys SO RESILIENCE IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Resilience in Children CY FEB 26-28, 2006 CL Arlington, VA SP NY Acad Sci, Brown Med Sch DE rhesus monkeys; fear; aggression; GxE interactions; species differences ID CEREBROSPINAL-FLUID MONOAMINE; NONHUMAN PRIMATE MODEL; ALCOHOL-CONSUMPTION; EARLY EXPERIENCE; PLASMA-CORTISOL; BEHAVIOR; STRESS; MACAQUES; POLYMORPHISM; AGGRESSION AB Recent research with both humans and rhesus monkeys has provided compelling evidence of gene-environment (GxE) interactions throughout development. For example, a specific polymorphism ("short" allele) in the promoter region of the serotonin transporter (5-HTT) gene is associated with deficits in neurobehavioral functioning during infancy and in poor control of aggression and low serotonin metabolism throughout juvenile and adolescent development in monkeys who were reared with peers but not in monkeys who were reared with their mothers and peers during infancy. In contrast, monkeys possessing the "long" allele of the 5-HTT gene exhibit normal neurobehavioral functioning, control of aggression, and serotonin metabolism regardless of their early social rearing history. One interpretation of these GxE interaction data is that the "long" 5-HTT allele somehow confers resiliency to adverse early attachment relationships on those individuals who carry it ("good genes"). An alternative interpretation of the same data is that secure attachment relationships somehow confer resiliency to individuals who carry alleles that may otherwise increase their risk for adverse developmental outcomes ("maternal buffering"). These two interpretations are not mutually exclusive, but the difference in their respective implications for developing prevention and even intervention strategies is considerable. Moreover, the allelic variation seen in certain genes in rhesus monkeys and humans but apparently not in other primate species may actually contribute to their remarkable adaptability and resilience at the species level. C1 NICHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. RP Suomi, SJ (reprint author), NICHD, Comparat Ethol Lab, NIH, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM ssl48k@nih.gov FU Intramural NIH HHS NR 30 TC 133 Z9 136 U1 1 U2 37 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-643-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1094 BP 52 EP 62 DI 10.1196/annals.1376.006 PG 11 WC Multidisciplinary Sciences; Neurosciences; Pediatrics SC Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BGA47 UT WOS:000245807000005 PM 17347341 ER PT S AU Enoch, MA AF Enoch, Mary-Anne BE Lester, BM Masten, AS McEwen, B TI Genetic and environmental influences on the development of alcoholism - Resilience vs. risk SO RESILIENCE IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Resilience in Children CY FEB 26-28, 2006 CL Arlington, VA SP NY Acad Sci, Brown Med Sch DE MAOA; HTTLPR; COMT; polymorphism; adolescents ID METHYLTRANSFERASE COMT GENE; AGE-OF-ONSET; SEROTONIN TRANSPORTER; ANTISOCIAL-BEHAVIOR; MALTREATED CHILDREN; FUNCTIONAL VARIANT; LIFE EVENTS; DRUG-ABUSE; JEWISH MEN; ASSOCIATION AB The physiological changes of adolescence may promote risk-taking behaviors, including binge drinking. Approximately 40% of alcoholics were already drinking heavily in late adolescence. Most cases of alcoholism are established by the age of 30 years with the peak prevalence at 18-23 years of age. Therefore the key time frame for the development, and prevention, of alcoholism lies in adolescence and young adulthood. Severe childhood stressors have been associated with increased vulnerability to addiction, however, not all stress-exposed children go on to develop alcoholism. Origins of resilience can be both genetic (variation in alcohol-metabolizing genes, increased susceptibility to alcohol's sedative effects) and environmental (lack of alcohol availability, positive peer and parental support). Genetic vulnerability is likely to be conferred by multiple genes of small to modest effects, possibly only apparent in gene-environment interactions. For example, it has been shown that childhood maltreatment interacts with a monoamine oxidase A (MAOA) gene variant to predict antisocial behavior that is often associated with alcoholism, and an interaction between early life stress and a serotonin transporter promoter variant predicts alcohol abuse in nonhuman primates and depression in humans. In addition, a common Met158 variant in the catechol-O-methyltransferase (COMT) gene can confer both risk and resilience to alcoholism in different drinking environments. It is likely that a complex mix of gene(s)-environment(s) interactions underlie addiction vulnerability and development. Risk-resilience factors can best be determined in longitudinal studies, preferably starting during pregnancy. This kind of research is important for planning future measures to prevent harmful drinking in adolescence. C1 NIAAA, NIH, DICBR, LNG, Bethesda, MD 20892 USA. RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM maenoch@niaaa.nih.gov NR 41 TC 92 Z9 94 U1 3 U2 25 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-643-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1094 BP 193 EP 201 DI 10.1196/annals.1376.019 PG 9 WC Multidisciplinary Sciences; Neurosciences; Pediatrics SC Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BGA47 UT WOS:000245807000015 PM 17347351 ER PT S AU LaGasse, LL Hammond, J Liu, J Lester, BM Shankaran, S Bada, H Bauer, C Higgins, R Das, A AF LaGasse, Linda L. Hammond, Jane Liu, Jing Lester, Barry M. Shankaran, Seetha Bada, Henrietta Bauer, Charles Higgins, Rosemary Das, Abhik BE Lester, BM Masten, AS McEwen, B TI Violence and delinquency, early onset drug use, and psychopathology in drug-exposed youth at 11 years SO RESILIENCE IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Resilience in Children CY FEB 26-28, 2006 CL Arlington, VA SP NY Acad Sci, Brown Med Sch DE prenatal drug exposure; cocaine; violence; preadolescence; delinquency; early drug use; psychopathology; resilience ID MATERNAL LIFE-STYLE; PREGNANCY AB In this first study of violence and resilience in 517 youth exposed to cocaine and other drugs during pregnancy, we identified specific links between four types of violence and delinquency, drug use, and psychopathology in early adolescence. Further, positive and interpersonal attributes promoted resilience in the face of exposure to violence and other risks. This study provides new evidence for the impact of violence as well as resilience against disruptive forms of psychopathology and behavior. C1 Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Providence, RI 02905 USA. Brown Med Sch, Providence, RI USA. Res Triangle Inst Int, Res Triangle Pk, NC USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Tennessee, Sch Med, Memphis, TN USA. Univ Miami, Sch Med, Miami, FL USA. NICHHD, Bethesda, MD 20892 USA. RP LaGasse, LL (reprint author), Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. EM Linda_Lagasse@brown.edu FU NIDA NIH HHS [U10 DA024119] NR 11 TC 16 Z9 16 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-643-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1094 BP 313 EP 318 DI 10.1196/annals.1376.041 PG 6 WC Multidisciplinary Sciences; Neurosciences; Pediatrics SC Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BGA47 UT WOS:000245807000032 PM 17347368 ER PT S AU Sheinkopf, SJ Lagasse, LL Lester, BM Liu, J Seifer, R Bauer, CR Shankaran, S Bada, H Higgins, R Das, A AF Sheinkopf, Stephen J. Lagasse, Linda L. Lester, Barry M. Liu, Jing Seifer, Ronald Bauer, Charles R. Shankaran, Seetha Bada, Henrietta Higgins, Rosemary Das, Abhik BE Lester, BM Masten, AS McEwen, B TI Prenatal cocaine exposure - Cardiorespiratory function and resilience SO RESILIENCE IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Resilience in Children CY FEB 26-28, 2006 CL Arlington, VA SP NY Acad Sci, Brown Med Sch DE prenatal drug exposure; cocaine; cumulative risk; children; vagal tone; heart rate variability; developmental outcome ID CARDIAC VAGAL TONE; BEHAVIOR; CHILDREN; MODEL AB Cardiac vagal tone (VT) was studied as a resilience factor in children prenatally exposed to cocaine and nonexposed controls (n = 550). A cumulative risk index was derived and used to classify children as high versus low risk. VT was measured during mildly stressful observations at 1 and 36 months of age. Children were classified as having consistently high, consistently low, or fluctuating VT. Risk and VT interacted to predict adaptive behaviors. For high-risk children, low VT was related to higher ratings of adaptive behaviors. This finding suggests that regulatory functioning, as indexed by VT, may be a protective factor in prenatal CE. C1 Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Providence, RI 02905 USA. Brown Med Sch, Providence, RI USA. EP Bradley Hosp, E Providence, RI USA. Univ Miami, Sch Med, Miami, FL 33152 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Tennessee, Sch Med, Memphis, TN USA. NICHHD, Bethesda, MD 20892 USA. Res Triangle Inst, Rockville, MD USA. RP Sheinkopf, SJ (reprint author), Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, 101 Dudley St, Providence, RI 02905 USA. EM Stephen_Sheinkopf@brown.edu OI Seifer, Ronald/0000-0003-4879-2839 FU NIDA NIH HHS [U10 DA024119] NR 8 TC 1 Z9 1 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-643-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1094 BP 354 EP 358 DI 10.1196/annals.1376.049 PG 5 WC Multidisciplinary Sciences; Neurosciences; Pediatrics SC Science & Technology - Other Topics; Neurosciences & Neurology; Pediatrics GA BGA47 UT WOS:000245807000040 PM 17347376 ER PT S AU Egwuagu, CE Yu, CH Mahdi, RM Mameza, M Eseonu, C Takase, H Ebong, S AF Egwuagu, CE Yu, CH Mahdi, RM Mameza, M Eseonu, C Takase, H Ebong, S BE Hollyfield, JG Anderson, RE LaVail, MM TI Cytokine-induced retinal degeneration: Role of suppressors of cytokine signaling (SOCS) proteins in protection of the neuroretina SO RETINAL DEGENERATIVE DISEASES SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium on Retinal Degeneration CY AUG 23-28, 2004 CL Perth, AUSTRALIA SP Fdn Fighting Blindness, Owings Mills ID INTERFERON-GAMMA; NEURONAL DIFFERENTIATION; CELLS; OUTGROWTH; PATHWAYS; UVEITIS; RATS C1 NEI, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 0-387-28464-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2006 VL 572 BP 275 EP 281 PG 7 WC Medicine, Research & Experimental; Microbiology; Ophthalmology SC Research & Experimental Medicine; Microbiology; Ophthalmology GA BDY95 UT WOS:000236276600038 PM 17249584 ER PT J AU Bao, J Kopnisky, K AF Bao, Jing Kopnisky, Kathy TI NIMH funding opportunities for NeuroAIDS therapeutics development research SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Bao, Jing; Kopnisky, Kathy] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P72 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000181 ER PT J AU Berger, EA AF Berger, Edward A. TI Natural and engineered antibodies against HIV SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Berger, Edward A.] NIAID, Viral Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000101 ER PT J AU Boasso, A Hardy, AW Herbeuval, JP Anderson, SA Dolan, MJ Lifson, JD Fuchs, D Shearer, GM AF Boasso, A. Hardy, A. W. Herbeuval, J. P. Anderson, S. A. Dolan, M. J. Lifson, J. D. Fuchs, D. Shearer, G. M. TI HIV activates indoleamine 2,3-dioxygenease: inhibition of T cell proliferation by tryptophan starvation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Boasso, A.; Hardy, A. W.; Herbeuval, J. P.; Shearer, G. M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Anderson, S. A.; Dolan, M. J.] Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. [Anderson, S. A.; Dolan, M. J.] Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. [Lifson, J. D.] Innsbruck Med Univ, Div Biol Chem, Innsbruck, Austria. [Fuchs, D.] NCI, AIDS Vaccine Program, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P11 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000120 ER PT J AU Demberg, T Florese, RH Gomez-Roman, VR Larsen, K Van Rompay, KK Marthas, ML Venzon, D Kalyanaraman, V Pal, R Barnett, SW Cafaro, A Ensoli, B Robert-Guroff, M AF Demberg, Thorsten Florese, Ruth H. Gomez-Roman, V. Raul Larsen, Kay Van Rompay, Koen Ka Marthas, Marta L. Venzon, David Kalyanaraman, Vs Pal, Ranajit Barnett, Susan W. Cafaro, Aurelio Ensoli, Barbara Robert-Guroff, Marjiorie TI Non-neutralizing antibodies and vaccine-induced protection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Demberg, Thorsten; Florese, Ruth H.; Gomez-Roman, V. Raul; Robert-Guroff, Marjiorie] NIH, Vaccine Branch, Bethesda, MD 20892 USA. [Larsen, Kay] Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Van Rompay, Koen Ka; Marthas, Marta L.] Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Kalyanaraman, Vs; Pal, Ranajit] Adv BioSci Labs Inc, Kensington, MD 20895 USA. [Barnett, Susan W.] Novartis Vaccines, Emeryville, CA 94608 USA. [Cafaro, Aurelio; Ensoli, Barbara] Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy. RI Ensoli, Barbara/J-9169-2016; Cafaro, Aurelio/K-5314-2016 OI Ensoli, Barbara/0000-0002-0545-8737; NR 0 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S26 DI 10.1186/1742-4690-3-S1-S26 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000027 ER PT J AU Felber, BK von Gegerfelt, A Valentin, A Rosati, M Alicea, C Bergamaschi, C Patel, V Jalah, R Pavlakis, GN AF Felber, Barbara K. von Gegerfelt, Agneta Valentin, Antonio Rosati, Margherita Alicea, Candido Bergamaschi, Cristina Patel, Vainav Jalah, Rashmi Pavlakis, George N. TI Preservation of a subset of SIV-specific central memory CD4+T cells correlates with control of viremia in SIVmac251 infected macaques SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Felber, Barbara K.; Alicea, Candido; Jalah, Rashmi] NCI, Human Retrovirus Pathogenesis Sect, Ctr Canc Res, Frederick, MD 21701 USA. [von Gegerfelt, Agneta; Valentin, Antonio; Rosati, Margherita; Bergamaschi, Cristina; Patel, Vainav; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S93 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000094 ER PT J AU Garg, H Blumenthal, R AF Garg, Himanshu Blumenthal, Robert TI Mutational analysis of HIV-1 gp41 mediated apoptosis and its correlation with fusion/hemifusion SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Garg, Himanshu; Blumenthal, Robert] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S89 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000090 ER PT J AU Hamer, D McHugh, L McKinney, M Richards, C Schully, K Lagenaur, L Rao, S AF Hamer, Dean McHugh, Louise McKinney, Margaret Richards, Chris Schully, Kevin Lagenaur, Laurel Rao, Srinivas TI Live microbial microbicides for HIV SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Hamer, Dean; McHugh, Louise; McKinney, Margaret; Richards, Chris; Schully, Kevin] NCI, Biochem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Lagenaur, Laurel] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Rao, Srinivas] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S50 DI 10.1186/1742-4690-3-S1-S50 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000051 ER PT J AU Herbeuval, JP Boasso, A Hardy, AW Shearer, GM AF Herbeuval, Jean-Philippe Boasso, Adriano Hardy, Andrew W. Shearer, Gene M. TI HIV-1 pathogenesis: IFN-alpha-dependent and -independent mechanisms of T cell death and unresponsiveness SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Herbeuval, Jean-Philippe; Boasso, Adriano; Hardy, Andrew W.; Shearer, Gene M.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Herbeuval, Jean-Philippe] Univ Paris, Hop Necker Enfants Malad, CNRS, UMR 8147, F-75252 Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S44 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000045 ER PT J AU Jacobson, S AF Jacobson, Steven TI The emerging role of HHV-6 in neurologic disease: lesson from multiple sclerosis and epilepsy SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Viral Immunol Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S64 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000065 ER PT J AU Lusso, P Crowley, RW Malnati, MS Ponzoni, M Di Serio, C Biancotto, A Markham, PD Gallo, RC AF Lusso, Paolo Crowley, Richard W. Malnati, Mauro S. Ponzoni, Maurilio Di Serio, Clelia Biancotto, Angelique Markham, Phillip D. Gallo, Robert C. TI Accelerated progression to AIDS in macaques coinfected with simian immunodeficiency virus and human herpesvirus 6A SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Crowley, Richard W.; Gallo, Robert C.] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Lusso, Paolo; Malnati, Mauro S.; Ponzoni, Maurilio; Di Serio, Clelia] Ist Sci San Raffaele, Dept Biotechnol, I-20132 Milan, Italy. [Biancotto, Angelique] NICHHD, Lab Cellular & Mol Biophys, Natl Inst Hlth, Bethesda, MD 20892 USA. [Markham, Phillip D.] Adv BioSci Labs Inc, Kensington, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S62 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000063 ER PT J AU Lutwama, F Serwadda, R Nanyonjo, A Shihab, H Kikawa, C Kamya, M Quinn, T Spacek, L Mayanja, H AF Lutwama, F. Serwadda, R. Nanyonjo, A. Shihab, H. Kikawa, C. Kamya, M. Quinn, T. Spacek, L. Mayanja, H. TI Low-cost dynabead and cytospheres compared to FACSCount to monitor patients on antiretroviral therapy at a public clinic in Kampala, Uganda SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Lutwama, F.; Serwadda, R.; Nanyonjo, A.; Shihab, H.; Kikawa, C.] Acad Alliance AIDS Care & Prevent, Kampala, Uganda. [Spacek, L.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Kamya, M.; Mayanja, H.] Makerere Univ, Kampala, Uganda. [Quinn, T.] Johns Hopkins Med Inst, Bethesda, MD USA. [Quinn, T.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P37 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000146 ER PT J AU Margolis, L AF Margolis, Leonid TI HIV interactions with herpes viruses in human lyphoid tissues SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Margolis, Leonid] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S63 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000064 ER PT J AU Morrow, M Valentin, A Little, R Yarchoan, R Pavlakis, GN AF Morrow, M. Valentin, A. Little, R. Yarchoan, R. Pavlakis, G. N. TI Preferential depletion of a splenic marginal zone-like peripheral blood CD27+B220-memory B cell population in HIV-1 infected individuals SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Morrow, M.; Valentin, A.; Pavlakis, G. N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA. [Little, R.; Yarchoan, R.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S97 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000098 ER PT J AU Murphy, P AF Murphy, Philip TI Chemokine receptor CCR5 mediates resistance to West Nile Virus infection in mouse and man SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Murphy, Philip] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S2 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000003 ER PT J AU Nabel, GJ AF Nabel, Gary J. TI A multiclade DNA/Ad vaccines for AIDS: the present and next generation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Nabel, Gary J.] NIAID, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S19 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000020 ER PT J AU Oh, S Perera, LP Waldmann, TA Berzofsky, JA AF Oh, SangKon Perera, Liyanage P. Waldmann, Thomas A. Berzofsky, Jay A. TI Overcoming CD4 deficiency to induce long-lived memory CD8(+) CTL SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Oh, SangKon; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Perera, Liyanage P.; Waldmann, Thomas A.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S17 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000018 ER PT J AU Olivero, OA Borojerdi, JP Semino-Mora, C Ward, Y Poirier, MC AF Olivero, Ofelia A. Borojerdi, Jennifer P. Semino-Mora, Cristina Ward, Yvonna Poirier, Miriam C. TI Genomic instability induced by AZT in cultured normal human mammary epithelial cells (NHMECs) generates aneuploidy SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Olivero, Ofelia A.; Borojerdi, Jennifer P.; Ward, Yvonna; Poirier, Miriam C.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Semino-Mora, Cristina] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P48 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000157 ER PT J AU Paul, WE Yamane, H Guo, LY Zhu, JF AF Paul, William E. Yamane, Hidehiro Guo, Liying Zhu, Jinfang TI Transcriptional regulation of Th2 differentiation SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Paul, William E.; Yamane, Hidehiro; Guo, Liying; Zhu, Jinfang] NIH, Immunol Lab, NIAID, Bethesda, MD 20892 USA. RI Zhu, Jinfang/B-7574-2012 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 2006 VL 3 SU 1 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000100 ER PT J AU Poirier, MC Shearer, GM Hardy, AW Olivero, OA Walker, DM Walker, VE AF Poirier, Miriam C. Shearer, Gene M. Hardy, Andrew W. Olivero, Ofelia A. Walker, Dale M. Walker, Vernon E. TI Antiretroviral activity of aminothiols, WR2721 and WR1065 SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Poirier, Miriam C.; Shearer, Gene M.; Hardy, Andrew W.; Olivero, Ofelia A.] Natl Canc Inst, NIH, Bethesda, MD 20892 USA. [Walker, Dale M.; Walker, Vernon E.] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA P78 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000187 ER PT J AU Quinn, TC AF Quinn, Thomas C. TI Male circumcision as a preventive measure limiting HIV transmission SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Quinn, Thomas C.] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S109 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000110 ER PT J AU Roederer, M AF Roederer, Mario TI Acute infection by SIV: massive immunological damage SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Roederer, Mario] NCI, Immuno Technol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S18 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000019 ER PT J AU Wahren, B Brave, A Boberg, A Rollman, E Birx, D Cox, J Robb, M Moss, B Blomberg, P Biberfeldt, G Sandstroem, E AF Wahren, Britta Brave, Andreas Boberg, Andreas Rollman, Erik Birx, Deborah Cox, Josephine Robb, Merlin Moss, Bernhard Blomberg, Pontus Biberfeldt, Gunnel Sandstroem, Eric TI Potent cellular and humoral immunity against HIV-1 elicited in mice by a DNA-prime/MVA-boost vaccine regimen intended for human use SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Wahren, Britta; Brave, Andreas; Boberg, Andreas; Rollman, Erik; Blomberg, Pontus; Biberfeldt, Gunnel; Sandstroem, Eric] Karolinska Inst, Stockholm, Sweden. [Wahren, Britta; Brave, Andreas; Boberg, Andreas; Rollman, Erik; Blomberg, Pontus; Biberfeldt, Gunnel; Sandstroem, Eric] Karolinska Univ Hosp, Swedish Inst Infect Dis Control, Stockholm, Sweden. [Birx, Deborah; Cox, Josephine; Robb, Merlin; Moss, Bernhard] NIH, Silver Spring, MD USA. [Birx, Deborah; Cox, Josephine; Robb, Merlin; Moss, Bernhard] Walter Reed Army Inst Res, Silver Spring, MD USA. EM Britta.Wahren@smi.ki.se NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S83 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000084 ER PT J AU Xu, Q Lagenaur, L Liu, X Liu, Y Yu, R Wells, K Tsai, D Sweeney, Y Rao, S Hamer, D Patton, D Parks, T Lee, P AF Xu, Qiang Lagenaur, Laurel Liu, Xiaowen Liu, Yang Yu, Rosa Wells, Kim Tsai, Daniel Sweeney, Yvonne Rao, Srinivas Hamer, Dean Patton, Dorothy Parks, Thomas Lee, Peter TI Development of a live topical microbicide for women SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Xu, Qiang; Lagenaur, Laurel; Liu, Xiaowen; Liu, Yang; Yu, Rosa; Wells, Kim; Tsai, Daniel; Parks, Thomas; Lee, Peter] Osel Inc, Santa Clara, CA 95054 USA. [Sweeney, Yvonne; Patton, Dorothy] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Rao, Srinivas] NIH, Lab Anim Med, Bethesda, MD 20892 USA. [Hamer, Dean] NCI, NIH, Bethesda, MD 20892 USA. EM qxu@oselinc.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S37 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000038 ER PT J AU Zhang, MY Vu, B Huang, CC Sidirov, I Choudhly, V Kwong, PD Dimitrov, DS AF Zhang, Mei-Yun Vu, Bang Huang, Chih-chin Sidirov, Igor Choudhly, Vidita Kwong, Peter D. Dimitrov, Dimiter S. TI Identification of human monoclonal antibodies specific for CCR5 from an antibody library derived from HIV-infected long-term non-progressors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhang, Mei-Yun; Vu, Bang; Sidirov, Igor; Choudhly, Vidita; Dimitrov, Dimiter S.] NCI, Ctr Canc Res Nanobiol Program, Natl Inst Hlth, Frederick, MD 21702 USA. [Zhang, Mei-Yun] NCI, SAIC Frederick Inc, Natl Inst Hlth, Frederick, MD 21702 USA. [Huang, Chih-chin; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S61 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000062 ER PT J AU Zhou, TQ Xu, L Dey, B Hessell, AJ Majeed, S Van Ryk, D Xiang, SH Yang, XZ Zhang, MY Zwick, MB Arthos, J Burton, DR Dimitrov, DS Sodroski, J Wyatt, R Nabel, GJ Kwong, PD AF Zhou, Tongqing Xu, Ling Dey, Barna Hessell, Ann J. Majeed, Shahzad Van Ryk, Donald Xiang, Shi-Hua Yang, Xinzhen Zhang, Mei-Yun Zwick, Michael B. Arthos, James Burton, Dennis R. Dimitrov, Dimiter S. Sodroski, Joseph Wyatt, Richard Nabel, Gary J. Kwong, Peter D. TI Design clues from functional constraints and broadly neutralizing antibodies SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhou, Tongqing; Xu, Ling; Dey, Barna; Majeed, Shahzad; Wyatt, Richard; Nabel, Gary J.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Hessell, Ann J.; Zwick, Michael B.; Burton, Dennis R.] Scripps Res Inst, La Jolla, CA USA. [Van Ryk, Donald; Arthos, James] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. [Xiang, Shi-Hua; Yang, Xinzhen; Sodroski, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Mei-Yun; Dimitrov, Dimiter S.] NCI, Ctr Canc Res & Nanobiol Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S22 PG 2 WC Virology SC Virology GA V52ZS UT WOS:000203582000023 ER PT J AU Zhu, P Liu, J Bess, J Chertova, E Lifson, JD Grise, H Ofek, G Taylor, KA Roux, KH AF Zhu, P. Liu, J. Bess, J. Chertova, E. Lifson, J. D. Grise, H. Ofek, G. Taylor, K. A. Roux, K. H. TI The use of cryo electron microscopy to reveal the distribution and 3D structure of AIDS virus envelope spikes SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zhu, P.; Grise, H.; Taylor, K. A.; Roux, K. H.] Florida State Univ, Tallahassee, FL 32306 USA. [Bess, J.; Chertova, E.; Lifson, J. D.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Ofek, G.] NIAID, NIH, Bethesda, MD 20892 USA. RI Bess, Jr., Julian/B-5343-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2006 VL 3 SU 1 MA S5 PG 1 WC Virology SC Virology GA V52ZS UT WOS:000203582000006 ER PT J AU Carneiro-Proietti, ABF Catalan-Soares, BC Castro-Costa, CM Murphy, EL Sabino, EC Hisada, M Galvao-Castro, B Alcantara, LCJ Remondegui, C Verdonck, K Proietti, FA AF Carneiro-Proietti, ABF Catalan-Soares, BC Castro-Costa, CM Murphy, EL Sabino, EC Hisada, M Galvao-Castro, B Alcantara, LCJ Remondegui, C Verdonck, K Proietti, FA TI HTLV in the Americas: challenges and perspectives SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE Human T-lymphotropic virus 1; human T-lymphotropic virus 2; Retroviridae; RNA tumor viruses; blood donors; preventive medicine; Americas ID CELL LYMPHOTROPIC VIRUS; INTRAVENOUS-DRUG-USERS; MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; UNITED-STATES; I INFECTION; LEUKEMIA-VIRUS; BLOOD-DONORS; MOLECULAR EPIDEMIOLOGY; VERTICAL TRANSMISSION; NATURAL-HISTORY AB The first description of the human T-lymphotropic virus type 1 (HTLV-1) was made in 1980, followed closely by the discovery of HTLV-2, in 1982. Since then, the main characteristics of these viruses, commonly referred to as HTLV-1/2, have been thoroughly studied. Central and South America and the Caribbean are areas of high prevalence of HTLV-1 and HTVL-2 and have clusters of infected people. The major modes of transmission have been through sexual contact, blood, and mother to child via breast-feeding. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL), HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HTLV-associated uveitis as well as infectious dermatitis of children. More clarification is needed in the possible role of HTLV in rheumatologic, psychiatric, and infectious diseases. Since cures for ATL and HAM/TSP are lacking and no vaccine is available to prevent HTLV-1 and HTLV-2 transmission, these illnesses impose enormous social and financial costs on infected individuals, their families, and health care systems. For this reason, public health interventions aimed at counseling and educating high-risk individuals and populations are of vital importance. In the Americas this is especially important in the areas of high prevalence. C1 Fdn Hemominas, Belo Horizonte, MG, Brazil. Univ Fed Ceara, Fortaleza, Ceara, Brazil. Univ Calif San Francisco, San Francisco, CA 94143 USA. Fdn Pro Sangue, Hemoctr Sao Paulo, Sao Paulo, Brazil. NCI, NIH, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Fdn Oswaldo Cruz, Ctr Pewquisas Goncalo Moniz, Lab Avancado Saude Publ, Salvador, BA, Brazil. Fdn Bahiana Desenvolvimento Ciencias, Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil. Hosp San Roque, Serv Infectol & Med Trop, San Salvador De Jujuy, Argentina. Univ Peruana Cayetano Heredia, Inst Trop Med Alexander Von Humboldt, Lima, Peru. Univ Fed Minas Gerais, Dept Med Prevent & Social, Belo Horizonte, MG, Brazil. RP Carneiro-Proietti, ABF (reprint author), Rua Grao Para,882, BR-30150341 Belo Horizonte, MG, Brazil. EM presid@hemominas.mg.gov.br RI Sabino, Ester/F-7750-2010 OI Sabino, Ester/0000-0003-2623-5126 NR 70 TC 37 Z9 45 U1 2 U2 3 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 2006 VL 19 IS 1 BP 44 EP 53 DI 10.1590/S1020-49892006000100007 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 014DL UT WOS:000235458900008 PM 16536938 ER PT J AU Tortorici, MA Shapiro, RA Patton, JT AF Tortorici, MA Shapiro, RA Patton, JT TI A base-specific recognition signal in the 5 ' consensus sequence of rotavirus plus-strand RNAs promotes replication of the double-stranded RNA genome segments SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE rotavirus; RNA replication; initiation; RNA secondary structure ID PARALLEL GENETIC ALGORITHM; INFLUENZA-VIRUS POLYMERASE; MESSENGER-RNA; SECONDARY STRUCTURE; VIRAL-RNA; POLIOVIRUS RNA; OPEN CORES; PROTEIN; REQUIRES; PREDICTION AB Replica-lion of the segmented double-stranded (ds)RNA genome of rotavirus requires the viral RNA-dependent RNA polymerase (RdRP) to use 11 different (+)RNAs as templates for (-) strand synthesis. Complementary sequences proximal to the 5' and 3' termini are predicted to direct cyclization of the (+)RNAs by forming panhandle structures from which short highly conserved terminal sequences protrude as single-stranded tails. Cell-free replication assays indicate that such structural organization of the 5'- and 3'-ends is required for efficient dsRNA synthesis. Multiple specifically recognized elements exist at the 3'-end that promote dsRNA synthesis including RdRP-recruitment signals and a (-) strand initiation sequence. In contrast to the 3'-end, the role of the 5'-end has been less well defined. In this study, we determined that the 5'-end contains a base-specific recognition signal that plays an important role in the assembly of the RdRP and cofactors into a stable initiation complex for (-) strand synthesis. The 5' recognition signal is associated with the G2 residue of the 5'-consensus sequence, a residue that shows absolute conservation among all rotavirus groups (A, B, and C) examined to date. From our results, we suggest that rotavirus (+)RNA cyclization, although likely initiated by 5'- 3' nucleotide complementarity, may be stabilized by RdRP-dependent bridging. Given that synthesis of the H strand on the (+)RNA template will disrupt 5'-3' nucleotide interactions, RdRP-dependent bridging may be the sole mechanism by which the dsRNA product can be held in the necessary cyclized conformation required for efficient multiple rounds of transcription. C1 NIAID, Lab Infect Dis, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Patton, JT (reprint author), NIAID, Lab Infect Dis, NIH, 50 S Dr MSC 8026,Room 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 NR 49 TC 32 Z9 36 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JAN PY 2006 VL 12 IS 1 BP 133 EP 146 DI 10.1261/rna.2122606 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 002YO UT WOS:000234648500014 PM 16301600 ER PT S AU Storz, G Gottesman, S AF Storz, Gisela Gottesman, Susan BE Gesteland, RF Cech, TR Atkins, JF TI Versatile Roles of Small RNA Regulators in Bacteria SO RNA WORLD, THIRD EDITION SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID SM-LIKE PROTEIN; SMALL ANTISENSE RNA; ENTERICA SEROVAR TYPHIMURIUM; PSEUDOMONAS-FLUORESCENS CHA0; BLOCKS RIBOSOME BINDING; ESCHERICHIA-COLI; MESSENGER-RNA; GENE-EXPRESSION; 6S RNA; STAPHYLOCOCCUS-AUREUS C1 [Storz, Gisela] Natl Inst Child Hlth & Dev, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. [Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Storz, G (reprint author), Natl Inst Child Hlth & Dev, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 100 TC 24 Z9 24 U1 0 U2 1 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-739-6 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 43 BP 567 EP 594 PG 28 WC Biology SC Life Sciences & Biomedicine - Other Topics GA BNJ34 UT WOS:000274736900023 ER PT S AU Chernomordik, V Hebden, J Sviridov, A Weiss, G Gandjbakhche, A AF Chernomordik, V. Hebden, J. Sviridov, A. Weiss, G. Gandjbakhche, A. BE Zimnyakov, DA Khlebtsov, NG TI Influence of tissue anisotropy on photon migration SO SARATOV FALL MEETING 2005: COHERENT OPTICS OF ORDERED AND RANDOM MEDIA VI SE Proceedings of SPIE LA English DT Proceedings Paper CT 2005 Saratov Fall Meeting CY SEP 27-30, 2005 CL Saratov, RUSSIA SP Russian Fdn Basic Res, SPIE Russia Chapter, Saratov State Univ SPIE Student Chapter, CRDF, US Civilian Res & Dev Fdn Independent States Former Soviet Union, IEEE MTT, ED, AP, CPMT Saratov Penza Chapter, TECHNOSERV S, Ltd, Almus Ltd, Eurdite 96, Ltd, STANDA Ltd, Chernyshevsky Saratov State Univ, RAS, Inst Precis Mech & Control, Russian Minist Educ Res Educ Ctr Nonlinear Dynam & Biophys, Volga Reg Ctr New Informat Technologies, Inst Business & Business Adm Saratov State Tech Univ DE optical properties; polarized videoreflectometry; equi-intensity ellipses ID OPTICAL-PROPERTIES; MEDICINE; LIGHT; MODEL; SKIN AB Some recent advances in the optical analysis of anisotropic media, especially those, related with work of our group at National Institutes of Health, are presented. Comparison of theoretical formulas, obtained from random walk theory with available time-resolved (transmission mode) and polarization CW (reflectance mode) experimental data is discussed. C1 Natl Inst Hlth, Bethesda, MD USA. RP Chernomordik, V (reprint author), Natl Inst Hlth, Bethesda, MD USA. NR 14 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 0-8194-6216-0 J9 PROC SPIE PY 2006 VL 6164 AR 61640C DI 10.1117/12.695015 PG 6 WC Optics SC Optics GA BEX09 UT WOS:000239921200012 ER PT J AU Shore, D AF Shore, D TI Ethical issues in schizophrenia research: A commentary on some current concerns SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material DE research ethics; schizophrenia; placebo; consent capacity ID PLACEBO-CONTROLLED TRIALS; INFORMED-CONSENT; RESEARCH PARTICIPATION; NIMH PERSPECTIVE; PSYCHIATRISTS AB An essential aspect of research on schizophrenia is ensuring that worthwhile scientific studies are done in a way that does not place vulnerable individuals at unreasonable risk. It is important to educate researchers, advocates, potential participants, reviewers, IRBs, and the general public about ethical principles and controversial issues as they impact research on schizophrenia. Federal regulations mandate IRB consideration of "the special problems of research involving... mentally disabled persons..." (45CFR46.111a3). In recent years, there has been a greater focus on subject monitoring to improve safeguards and minimize risks. The process of informed consent is also going through a process of evolution, in order to help ensure that participants are as aware as possible of key aspects of a study, including risks, benefits, alternatives, purpose and design, etc. We focus here on a few of the issues that are current, are relevant to schizophrenia research, and merit additional empirical study. They include medication discontinuation and placebo control designs, compensation for participation, and capacity to consent. C1 Georgetown Univ, Washington, DC 20057 USA. RP Shore, D (reprint author), NIMH, 6001 Execut Blvd,8221, Bethesda, MD 20892 USA. EM DShore@mail.nih.gov NR 13 TC 9 Z9 11 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2006 VL 32 IS 1 BP 26 EP 29 DI 10.1093/schbul/sbj031 PG 4 WC Psychiatry SC Psychiatry GA 000BK UT WOS:000234435700007 PM 16319376 ER PT J AU Miller, FG Wendler, D AF Miller, FG Wendler, D TI The relevance of empirical research in bioethics SO SCHIZOPHRENIA BULLETIN LA English DT Article DE research ethics; empirical ethics research; stored samples; placebo-controlled trials; therapeutic misconception ID PLACEBO-CONTROLLED TRIALS; STORED BIOLOGICAL SAMPLES; INFORMED-CONSENT; THERAPEUTIC MISCONCEPTION; GENETIC RESEARCH; CLINICAL-TRIALS; POPULATION; ETHICS; TISSUE AB Empirical research related to ethical issues in clinical research has grown dramatically in recent years. However, little attention has been devoted to the ethical relevance of the findings from this research. In order to examine the value and limitations of ethics-related empirical research, we discuss 3 case studies involving research with stored biological samples, placebo-controlled trials, and the idea of the therapeutic misconception. C1 NIH, Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU Intramural NIH HHS NR 27 TC 12 Z9 13 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2006 VL 32 IS 1 BP 37 EP 41 DI 10.1093/schbul/sbj004 PG 5 WC Psychiatry SC Psychiatry GA 000BK UT WOS:000234435700009 PM 16192410 ER PT J AU Honea, RA Meyer-Lindenberg, A Hobbs, KK Pezawas, L Verchinski, BA Goldman, A Mattay, VS Weinberger, D Callicott, J AF Honea, RA Meyer-Lindenberg, A Hobbs, KK Pezawas, L Verchinski, BA Goldman, A Mattay, VS Weinberger, D Callicott, J TI Temporal and prefrontal cortex gray matter abnormalities in patients with schizophrenia and their unaffected siblings; An optimized voxel-based morphometry study SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. EM honear@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 158 EP 159 PG 2 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524700391 ER PT J AU Webster, MJ Elashoff, M Ryan, MM Khaitchovitch, P Paabo, S Bahn, S Weickert, CS AF Webster, MJ Elashoff, M Ryan, MM Khaitchovitch, P Paabo, S Bahn, S Weickert, CS TI A microarray study examining normal gene expression in prefrontal cortex across the human lifespan SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 USUHS, Stanley Lab Brain Res, Bethesda, MD 20892 USA. Elashoff Consulting, Gaithersburg, MD USA. Univ Cambridge, Inst Biotechnol, Cambridge, England. Max Planck Inst Evolutionary Anthropol, Dept Evolutiionary Genet, Leipzig, Germany. NIMH, MiNDS Unit, Bethesda, MD USA. EM websterm@stanleyresearch.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 287 EP 287 PG 1 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524701278 ER PT J AU Fink-Jensen, A Sorensen, L Bay-Richter, C Frikke-Schmidt, H Wess, J Woldbye, DP Wortwein, G AF Fink-Jensen, A Sorensen, L Bay-Richter, C Frikke-Schmidt, H Wess, J Woldbye, DP Wortwein, G TI Involvement of the M5 muscarinic receptor in cocaine and amphetamine induced behaviour: Studies in M5 knockout mice backcrossed to the C57BL/6NTac strain SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 13th Biennial Winter Workshop on Schizophrenia Research CY FEB 04-10, 2006 CL Davos, SWITZERLAND C1 Univ Hosp, Rigshosp, Lab Neuropsychiat, Copenhagen, Denmark. NIDDK, Mol Signalling Sect, Lab Bioorgan Chem, Bethesda, MD USA. EM a.fink-jensen@dadlnet.dk NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 2006 VL 81 SU S BP 301 EP 302 PG 2 WC Psychiatry SC Psychiatry GA 015AQ UT WOS:000235524701316 ER PT J AU Harper-Mangels, R Brinkman, J Gonzalez-Lima, E Oliverio, E Swope, D AF Harper-Mangels, R Brinkman, J Gonzalez-Lima, E Oliverio, E Swope, D TI A 10-step plan for better postdoc training SO SCIENTIST LA English DT Editorial Material C1 Northwestern Univ, Inst Neurosci, Chicago, IL 60611 USA. Florida Atlantic Univ, Boca Raton, FL 33431 USA. Univ British Columbia, St Pauls Hosp, Ctr Cardiovasc & Pulm Res, Vancouver, BC V5Z 1M9, Canada. Univ Texas, Dept Psychol, Austin, TX 78712 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Harper-Mangels, R (reprint author), Northwestern Univ, Inst Neurosci, Chicago, IL 60611 USA. EM rmangals@the-scientist.com NR 3 TC 1 Z9 1 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JAN PY 2006 VL 20 IS 1 BP 24 EP 25 PG 2 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 995VI UT WOS:000234132100009 ER PT S AU Marchand, C Pommier, Y AF Marchand, Christophe Pommier, Yves BE Waring, MJ TI Interfacial Inhibitors of Human Topoisomerase I SO SEQUENCE-SPECIFIC DNA BINDING AGENTS SE RSC Biomolecular Sciences LA English DT Article; Book Chapter ID CLEAVAGE COMPLEXES; CAMPTOTHECIN RESISTANCE; BIOLOGICAL EVALUATION; DNA TOPOISOMERASES; STRUCTURAL BASIS; STRAND BREAKS; CELL-LINES; MECHANISM; PROTEIN; INDENOISOQUINOLINE C1 [Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Marchand, C (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. RI Marchand, Christophe/D-8559-2016 NR 48 TC 1 Z9 1 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1757-7152 BN 978-1-84755-530-4 J9 RSC BIOMOL SCI JI RSC Biomol. Sci. PY 2006 BP 29 EP 43 D2 10.1039/9781847555304 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BKV59 UT WOS:000269401700003 ER PT J AU Chow, CC Coombes, S AF Chow, Carson C. Coombes, S. TI Existence and wandering of bumps in a spiking neural network model SO SIAM JOURNAL ON APPLIED DYNAMICAL SYSTEMS LA English DT Article DE spiking neural network; bump solutions; working memory; lighthouse model ID WORKING-MEMORY; NEURONAL NETWORKS; PATTERN-FORMATION; TRAVELING FRONTS; STANDING PULSES; DYNAMICS; STABILITY; REPRESENTATION; POPULATIONS; ELEMENTS AB We study spatially localized states of a spiking neuronal network populated by a pulse-coupled phase oscillator known as the lighthouse model. We show that in the limit of slow synaptic interactions in the continuum limit the dynamics reduce to those of the standard Amari model. For nonslow synaptic connections we are able to go beyond the standard. ring rate analysis of localized solutions, allowing us to explicitly construct a family of coexisting one-bump solutions and then track bump width and. ring pattern as a function of system parameters. We also present an analysis of the model on a discrete lattice. We show that multiple width bump states can coexist, and uncover a mechanism for bump wandering linked to the speed of synaptic processing. Moreover, beyond a wandering transition point we show that the bump undergoes an effective random walk with a diffusion coefficient that scales exponentially with the rate of synaptic processing and linearly with the lattice spacing. C1 NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. Univ Nottingham, Dept Math Sci, Nottingham NG7 2RD, England. RP Chow, CC (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM carsonc@mail.nih.gov; stephen.coombes@nottingham.ac.uk RI Chow, Carson/A-7970-2009; Coombes, Stephen/J-1859-2012 OI Coombes, Stephen/0000-0003-1610-7665 NR 33 TC 21 Z9 21 U1 0 U2 1 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 1536-0040 J9 SIAM J APPL DYN SYST JI SIAM J. Appl. Dyn. Syst. PY 2006 VL 5 IS 4 BP 552 EP 574 DI 10.1137/060654347 PG 23 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA 142DQ UT WOS:000244629800002 ER PT S AU Juan, AH Lei, HY Bhargava, P Lebrun, M Ruddle, FH AF Juan, Aster H. Lei, Haiyan Bhargava, Prerna Lebrun, Marielle Ruddle, Frank H. BE Zaidi, M TI Multiple roles of Hoxc8 in skeletal development SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE Hoxc8; axial skeleton; osteoblast; Wnt; BMP ID GENE-EXPRESSION AB We are interested in investigating the function of Hoxc8 in skeletogenesis during mouse development. Previous studies have shown that deregulation of Hoxc8 expression in the mouse leads to several skeletal defects, such as homeotic transformation in the thoracic vertebrae, abnormal development of the rib cage, and overproliferation of chondrocytes in the hypertrophic area. By deleting a crucial enhancer of Hoxc8 in vivo, we found that precise temporal expression of Hoxc8 is important for determining the correct identity of the vertebral column in early embryos. We also identified downstream targets of Hoxc8 relevant to osteoblast differentiation at later developmental stages. C1 Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA. Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. Univ Liege, Inst Pathol, Lab Virol & Immunol, B-4000 Liege, Belgium. RP Juan, AH (reprint author), NIH, 50 S Dr,Room 1148, Bethesda, MD 20892 USA. EM juana2@mail.nih.gov FU NIEHS NIH HHS [T32 ES016645] NR 6 TC 10 Z9 10 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 87 EP 94 DI 10.1196/annals.1346.046 PG 8 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200009 PM 16831908 ER PT S AU Blair, HC Carrington, JL AF Blair, Harry C. Carrington, Jill L. BE Zaidi, M TI Bone cell precursors and the pathophysiology of bone loss SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE stem cells; osteoblast; osteoclast; mesenchymal cells; aplastic anemia; autoimmunity; differentiation ID STEM-CELLS; OSTEOCLAST FORMATION; MULTIPLE-MYELOMA; GROWTH; PATHOGENESIS; DESTRUCTION; OSTEOBLASTS; MACROPHAGES; DEFICIENCY; ARTHRITIS AB In health, changes in bone formation and degradation rates are coupled and adequate cellular resources are available in the bone so that a change in bone formation rate occurs with an opposing change in resorption. On the other hand, the regulation of bone volume, particularly in pathological conditions, is dependent not only on the pathways that mediate terminal pathways of bone cell differentiation, but also on the availability of stem cells for allowing the differentiation to occur. Regulation of cell numbers in stem cell compartments and release of stem cells for differentiation of osteoblast or osteoclast precursors are not well understood, although it is clear that changes in stem cell numbers underlie pathological changes in bone mass. This may include effects of aging, fracture, metastatic disease, and autoimmune diseases on the precursor cell pools available for bone formation and degradation. Increases in osteoclast precursors or decreases in osteoblast precursors are common features of bone-losing states; increases in precursors may conversely occur during growth or repair processes. Rational therapy based on modifying stem cell populations may, when the processes are better understood, help prevent chronic bone-losing states and may also be of use in preventing or treating aplastic anemia and related conditions. C1 Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA 15213 USA. VA Med Ctr, Pittsburgh, PA 15213 USA. NIA, Biol Aging Program, NIH, Bethesda, MD 20892 USA. RP Blair, HC (reprint author), Univ Pittsburgh, Dept Pathol, 705 Scaife Hall, Pittsburgh, PA 15261 USA. EM hcblair@imap.pitt.edu FU NIA NIH HHS [AG12951]; NIAMS NIH HHS [AR47700] NR 23 TC 8 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 244 EP 249 DI 10.1196/annals.1346.028 PG 6 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200026 PM 16831925 ER PT S AU Margolis, RN Wimalawansa, SI AF Margolis, Ronald N. Wimalawansa, Sunil I. BE Zaidi, M TI Novel targets and therapeutics for bone loss SO SKELETAL DEVELOPMENT AND REMODELING IN HEALTH, DISEASE, AND AGING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Skeletal Development and Remodeling in Health, Disease and Aging CY MAY 18-21, 2005 CL New York, NY SP NY Acad Sci, Alliance Better Bone Hlth, Procter & Gamble Pharmaceut, Sanofi Aventis, Novartis Pharmaceut, Roche Pharmaceut, Merck & Co DE osteoporosis; novel therapies; RANKL; OPG; Wnt; leptin; prostaglandins; SERMs ID POSTMENOPAUSAL OSTEOPOROSIS; THERAPY; RANKL; OSTEOBLASTS; PREVENTION; RESORPTION; MASS AB Advances in the treatment of osteoporosis over the past decade have resulted in the generation of novel therapeutic agents aimed at providing both anticatabolic and anabolic effects in bone. In-depth understanding of the biology of key factors regulating bone metabolism has begun to reveal new approaches to treating this costly and debilitating disease. During the next decade we will observe the development and evolution of several new classes of therapeutic targets and agents to combat this disease. C1 NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Endocrinol, Dept Med, New Brunswick, NJ 08903 USA. RP Margolis, RN (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Room 693,Democracy 2, Bethesda, MD 20892 USA. EM rm76f@nih.gov OI Wimalawansa, Prof. Sunil/0000-0003-1096-8595 NR 23 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-583-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1068 BP 402 EP 409 DI 10.1196/annals.1346.040 PG 8 WC Multidisciplinary Sciences; Orthopedics SC Science & Technology - Other Topics; Orthopedics GA BFA92 UT WOS:000240548200040 PM 16831939 ER PT J AU Dalakas, MC AF Dalakas, Marinos C. BE SarziPuttini, P Doria, A Girolomoni, G Kuhn, A TI Dermatomyositis SO SKIN IN SYSTEMIC AUTOIMMUNE DISEASES SE Handbook of Systemic Autoimmune Diseases LA English DT Article; Book Chapter ID DOSE INTRAVENOUS IMMUNOGLOBULIN; EOSINOPHILIA-MYALGIA-SYNDROME; INTERSTITIAL LUNG-DISEASE; INCLUSION-BODY MYOSITIS; INFLAMMATORY MYOPATHIES; JUVENILE DERMATOMYOSITIS; MACROPHAGIC MYOFASCIITIS; CONTROLLED TRIAL; GAMMA-GLOBULIN; CYCLOSPORINE-A C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr,MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 71 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046192-2 J9 HANDB SYST AUTOIMMUN PY 2006 VL 5 BP 135 EP 145 DI 10.1016/S1571-5078(05)05011-7 PG 11 WC Dermatology; Immunology SC Dermatology; Immunology GA BCM50 UT WOS:000310709200012 ER PT J AU Fukunaga, M Horovitz, SG Jacco, DA Peter, V Susan, FC Balkin, TJ Duyn, JH AF Fukunaga, M. Horovitz, S. G. Jacco, D. A. Peter, V. Susan, F. C. Balkin, T. J. Duyn, J. H. TI Spatio-temporal characteristics of fMRI signal fluctuation during light sleep SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 NINDS, Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Behav Biol, Silver Spring, MD USA. RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 77 BP A25 EP A25 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700079 ER PT J AU Horovitz, SG Fukunaga, M de Zwart, ZJA van Gelderen, P Fulton, SC Balkin, TJ Duyn, JH AF Horovitz, S. G. Fukunaga, M. de Zwart, J. A. van Gelderen, P. Fulton, S. C. Balkin, T. J. Duyn, J. H. TI Bold fmri during awake rest and light sleep SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 NINDS, Adv MRI, LFMI, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Behav Biol, Silver Spring, MD USA. RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 108 BP A36 EP A36 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916700110 ER PT J AU Jamasebi, R Johnson, NL Romaniuk, J Kaffashi, F Twery, W Redline, S Loparo, K AF Jamasebi, R. Johnson, N. L. Romaniuk, J. Kaffashi, F. Twery, W. Redline, S. Loparo, K. TI A watermarking algorithm for polysomnography data SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Case Sch Engn, Cleveland, OH USA. Case Sch Medn, Cleveland, OH USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 1019 BP A348 EP A348 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701396 ER PT J AU Picchioni, D Carr, WS Horovitz, SG Fukunaga, M Duyn, JH Braun, AR Balkin, TJ AF Picchioni, D. Carr, W. S. Horovitz, S. G. Fukunaga, M. Duyn, J. H. Braun, A. R. Balkin, T. J. TI A preliminary assessment of the utility of FMRI to differentiate early and late stage-1 sleep SO SLEEP LA English DT Meeting Abstract CT 20th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 17-22, 2006 CL Salt Lake City, UT SP Associated Process Sleep Soc C1 Walter Reed Army Inst Res, Silver Spring, MD USA. NIH, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013 OI Fukunaga, Masaki/0000-0003-1010-2644 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2006 VL 29 SU S MA 1000 BP A342 EP A342 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 047ZH UT WOS:000237916701377 ER PT B AU Vgontzas, AN Pejovic, S Chrousos, GP AF Vgontzas, Alexandros N. Pejovic, Slobodanka Chrousos, George P. BA LeeChiong, T BF LeeChiong, T TI ENDOCRINE AND METABOLIC DISORDERS AND SLEEP SO SLEEP: A COMPREHENSIVE HANDBOOK LA English DT Article; Book Chapter ID POLYCYSTIC-OVARY-SYNDROME; EXCESSIVE DAYTIME SLEEPINESS; PRADER-WILLI-SYNDROME; DEPENDENT DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; SLOW-WAVE SLEEP; INSULIN-RESISTANCE; OBESE-PATIENTS; APNEA SYNDROME; CLINICAL-IMPLICATIONS C1 [Vgontzas, Alexandros N.] Penn State Coll Med, Dept Psychiat H073, Hershey, PA 17033 USA. [Pejovic, Slobodanka; Chrousos, George P.] NIH, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Coll Med, Dept Psychiat H073, 500 Univ Dr, Hershey, PA 17033 USA. NR 120 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-471-75172-4; 978-0-471-68371-1 PY 2006 BP 745 EP 757 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA BZE26 UT WOS:000301234900099 ER PT J AU Lindsey, MA Korr, WS Broitman, M Bone, L Green, A Leaf, PJ AF Lindsey, MA Korr, WS Broitman, M Bone, L Green, A Leaf, PJ TI Help-seeking behaviors and depression among African American adolescent boys SO SOCIAL WORK LA English DT Article DE adolescents; African Americans; depression; service use; social networks ID MENTAL-HEALTH-SERVICES; SOCIAL NETWORKS; SYMPTOMATOLOGY; CHILDREN; CARE AB This study examined the help-seeking behaviors of depressed, African American adolescents. Qualitative interviews were conducted with 18 urban, African American boys, ages 14 to 18, who were recruited from community-based mental health centers and after-school programs for youths. Interviews covered sociodemographic information, questions regarding depressive symptomotology, and open-ended questions derived from the Network-Episode Model-including knowledge, attitudes and behaviors related to problem recognition, help seeking, and perceptions of mental health services. Most often adolescents discussed their problems with their family and often received divergent messages about problem resolution; absent informal network resolution of their problems, professional help would be sought, and those receiving treatment were more likely to get support from friends but were less likely to tell friends that they were actually receiving care. Implications for social work research and practice are discussed. C1 Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA. Univ Illinois, Sch Social Work, Urbana, IL 61801 USA. NIMH, Div Extramural Affairs, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Lindsey, MA (reprint author), Univ Maryland, Sch Social Work, 525 W Redwood St, Baltimore, MD 21201 USA. EM mlindsey@ssw.umaryland.edu FU NIMH NIH HHS [1 R03 MH63593-01] NR 31 TC 42 Z9 43 U1 2 U2 10 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0037-8046 J9 SOC WORK JI Soc. Work PD JAN PY 2006 VL 51 IS 1 BP 49 EP 58 PG 10 WC Social Work SC Social Work GA 031JC UT WOS:000236699600006 PM 16512510 ER PT J AU Leung, DHY Qin, J AF Leung, DHY Qin, J TI Semi-parametric inference in a bivariate (multivariate) mixture model SO STATISTICA SINICA LA English DT Article DE empirical likelihood; multivariate mixture; semi-parametric; Shannon's mutual information ID SELECTION BIAS MODELS; EMPIRICAL LIKELIHOOD; CONFIDENCE-INTERVALS; DISTRIBUTIONS AB We consider estimation in a bivariate mixture model in which the component distributions can be decomposed into identical distributions. Previous approaches to estimation involve parametrizing the distributions. In this paper, we use a semi-parametric approach. The method is based on the exponential tilt model of Anderson (1979), where the log ratio of probability (density) functions from the bivariate components is linear in the observations. The proposed model does not require training samples, i.e., data with confirmed component membership. We show that in bivariate mixture models, parameters are identifiable. This is in contrast to previous works, where parameters are identifiable if and only if each univariate marginal model is identifiable (Teicher (1967)). C1 Singapore Management Univ, Sch Econ & Social Sci, Singapore 178903, Singapore. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Leung, DHY (reprint author), Singapore Management Univ, Sch Econ & Social Sci, 90 Stamford Rd, Singapore 178903, Singapore. EM denisleung@smu.edu.sg; jingqin@niaid.nih.gov RI LEUNG, Denis Heng Yan/D-1439-2009 NR 31 TC 4 Z9 4 U1 1 U2 3 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2006 VL 16 IS 1 BP 153 EP 163 PG 11 WC Statistics & Probability SC Mathematics GA 016PN UT WOS:000235632400010 ER PT J AU Liu, AY Hall, WJ Yu, KF Wu, CQ AF Liu, AY Hall, WJ Yu, KF Wu, CQ TI Estimation following a group sequential test for distributions in the one-parameter exponential family SO STATISTICA SINICA LA English DT Article DE clinical trials; completeness; laplace transform; minimum variance; truncation-adaptation; unbiased estimation ID CLINICAL-TRIALS; BIAS AB We consider unbiased estimation following a group sequential test for distributions in a one-parameter exponential family. We show that, for an estimable parameter function, there exists uniquely an unbiased estimator depending on the sufficient statistic and based on the truncation-adaptation criterion (Liu and Hall (1999)); moreover, this estimator is identical to one based on the Rao-Blackwell method. When completeness fails, we show that the uniformly minimum-variance unbiased estimator may not exist or might possess undesirable performance. A Phase-II clinical trial application with exponentially distributed responses is included. C1 NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China. RP Liu, AY (reprint author), NICHHD, Biometry & Math Stat Branch, Dept Hlth & Human Serv, 6100 Execut Blvd, Rockville, MD 20852 USA. EM Liua@mail.nih.gov; Hall@bst.rochester.edu; Yukf@mail.nih.gov; Wuch@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 24 TC 2 Z9 2 U1 1 U2 1 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2006 VL 16 IS 1 BP 165 EP 181 PG 17 WC Statistics & Probability SC Mathematics GA 016PN UT WOS:000235632400011 ER PT J AU Gigli, A Mariotto, A Clegg, LMX Tavilla, A Corazziari, I Capocaccia, R Hachey, M Scoppa, S AF Gigli, A Mariotto, A Clegg, LMX Tavilla, A Corazziari, I Capocaccia, R Hachey, M Scoppa, S TI Estimating the variance of cancer prevalence from population-based registries SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID TUMOR-REGISTRY; MORTALITY; DISEASE; PROGRAM AB Cancer prevalence is the proportion of people in a population diagnosed with cancer in the past and still alive. One way to estimate prevalence is via population-based registries, where data on diagnosis and life status of all incidence cases occurring in the covered population are collected. In this paper, a method to estimate the complete prevalence and its variance from population-based registries is presented. In order to obtain unbiased estimates of the complete prevalence, its calculation can be thought as made by three steps. Step 1 counts the incidence cases diagnosed during the period of registration and still alive. Step 2 estimates the expected number of survivors among cases lost to follow-up. Step 3 estimates the complete prevalence by taking into account cases diagnosed before the start of registration. The combination of steps 1+2 is defined as the counting method, to estimate the limited duration prevalence; step 3 is the completeness index method, to estimate the complete prevalence. For early established registries, steps 1+2 are more important than step 3, because observation time is long enough to include all past diagnosed cases still alive in the prevalence data. For more recently established registries, step 3 is by far the most critical because a large part of prevalence might have been diagnosed before the period of registration (Corazziari I, Mariotto A, Capocaccia R. Correcting the completeness bias of observed prevalence. Tumori 1999; 85: 370-81). The work by Clegg LX, Gail MH, Feuer EJ. Estimating the variance of disease-prevalence estimates from population-based registries. Biometrics 2002; 55: 1137-44. considers the problem of the variability of the estimated prevalence up to step 2. To our knowledge, no other work has considered the variability induced by correcting for the unobserved cases diagnosed before the period of registration, crucial to estimate the prevalence in recent registries. An analytic approach is considered to calculate the variance of step 3. A unified expression for the variance of the prevalence allowing for steps 1 through 3 is obtained. Some applications to cancer data are presented. C1 CNR, Ist Ric Popolaz & Polit Sociali, I-00198 Rome, Italy. Natl Canc Inst, Bethesda, MD USA. Ist Super Sanita, Ctr Nazl Epidemiol Sorveglianza & Promoz Salute, I-00161 Rome, Italy. Informat Management Serv Inc, Silver Spring, MD USA. RP Gigli, A (reprint author), CNR, Ist Ric Popolaz & Polit Sociali, Via Nizza 128, I-00198 Rome, Italy. EM a.gigli@irpps.cnr.it OI Gigli, Anna/0000-0003-4929-505X FU PHS HHS [263-MQ-117231-1] NR 25 TC 13 Z9 13 U1 0 U2 1 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2006 VL 15 IS 3 BP 235 EP 253 DI 10.1191/0962280206sm427oa PG 19 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 043CA UT WOS:000237575700002 PM 16768298 ER PT J AU Tiwari, RC Clegg, LX Zou, ZH AF Tiwari, Ram C. Clegg, Limin X. Zou, Zhaohui TI Efficient interval estimation for age-adjusted cancer rates SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID DIRECTLY STANDARDIZED RATES; CONFIDENCE-INTERVALS AB The age-adjusted cancer rates are defined as the weighted average of the age-specific cancer rates, where the weights are positive, known, and normalized so that their sum is 1. Fay and Feuer developed a confidence interval for a single age-adjusted rate based on the gamma approximation. Fay used the gamma approximations to construct an F interval for the ratio of two age-adjusted rates. Modifications of the gamma and F intervals are proposed and a simulation study is carried out to show that these modified gamma and modified F intervals are more efficient than the gamma and F intervals, respectively, in the sense that the proposed intervals have empirical coverage probabilities less than or equal to their counterparts, and that they also retain the nominal level. The normal and beta confidence intervals for a single age-adjusted rate are also provided, but they are shown to be slightly liberal. Finally, for comparing two correlated age-adjusted rates, the confidence intervals for the difference and for the ratio of the two age-adjusted rates are derived incorporating the correlation between the two rates. The proposed gamma and F intervals and the normal intervals for the correlated age-adjusted rates are recommended to be implemented in the Surveillance, Epidemiology and End Results Program of the National Cancer Institute. C1 Off Healthcare Inspect, OIG, Dept Vet Affairs, Washington, DC 20001 USA. NCI, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Clegg, LX (reprint author), Off Healthcare Inspect, OIG, Dept Vet Affairs, 801 1 St NW,Room 1013, Washington, DC 20001 USA. EM lin_clegg@va.gov NR 14 TC 166 Z9 169 U1 1 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2006 VL 15 IS 6 BP 547 EP 569 DI 10.1177/0962280206070621 PG 23 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 126OW UT WOS:000243525100002 PM 17260923 ER PT S AU Proschan, MA Lan, KKG Wittes, JT AF Proschan, Michael A. Lan, K. K. Gordan Wittes, Janet Turk BA Proschan, MA Lan, KKG Wittes, JT BF Proschan, MA Lan, KKG Wittes, JT TI Statistical Monitoring of Clinical Trials A Unified Approach Introduction SO STATISTICAL MONITORING OF CLINICAL TRIALS: A UNIFIED APPROACH SE Statistics for Biology and Health LA English DT Editorial Material; Book Chapter ID SAMPLE-SIZE REESTIMATION; I ERROR RATE; LINEAR RANK-TESTS; GROUP SEQUENTIAL-METHODS; CORONARY-ARTERY-DISEASE; SICKLE-CELL-ANEMIA; MYOCARDIAL-INFARCTION; ASYMPTOTIC PROPERTIES; CONFIDENCE-INTERVALS; RANDOMIZED-TRIALS C1 [Proschan, Michael A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Lan, K. K. Gordan] Johnson & Johnson, Raritan, NJ 08869 USA. [Wittes, Janet Turk] Stat Collaborat, Washington, DC 20036 USA. RP Proschan, MA (reprint author), NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. EM ProschaM@mail.nih.gov; glan@prdus.jnj.com NR 0 TC 101 Z9 101 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1431-8776 BN 978-0-387-44970-8 J9 STAT BIOL HEALTH JI Stat. Biol. Health PY 2006 BP 1 EP + D2 10.1007/978-0-387-44970-8 PG 15 WC Biology; Medicine, General & Internal; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; General & Internal Medicine; Mathematics GA BLQ50 UT WOS:000270807600001 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Data, Notation, and Some Basic Terms SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 3 EP + PG 16 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400003 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Distributions SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 15 EP 35 PG 21 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400004 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI STATISTICS IN MEDICINE Second Edition Foreword to the Second Edition SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP XVII EP XVIII PG 2 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400001 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI STATISTICS IN MEDICINE Second Edition Foreword to the First Edition SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP XIX EP XX PG 2 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400002 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Summary Statistics SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 37 EP 56 PG 20 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400005 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Confidence Intervals and Probability SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 57 EP 73 PG 17 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400006 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Hypothesis Testing: Concept and Practice SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 75 EP 92 PG 18 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400007 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Statistical Testing, Risks, and Odds in Medical Decisions SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 93 EP 114 PG 22 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400008 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Sample Size Required for a Study SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 115 EP 123 PG 9 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400009 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Statistical Prediction SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 125 EP 136 PG 12 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400010 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Epidemiology SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 137 EP 151 PG 15 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400011 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Reading Medical Articles SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 153 EP 164 PG 12 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400012 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Using the Reference Guide SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 187 EP 193 PG 7 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400013 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Planning Medical Studies SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 195 EP 212 PG 18 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400014 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Finding Probabilities of Error SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 213 EP 226 PG 14 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400015 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Confidence Intervals SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 227 EP 240 PG 14 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400016 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Categorical Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 241 EP 279 PG 39 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400017 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Ranked Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 281 EP 303 PG 23 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400018 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Means of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 305 EP 329 PG 25 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400019 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Multifactor Tests on Means of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 331 EP 354 PG 24 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400020 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on Variances of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 355 EP 367 PG 13 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400021 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Tests on the Distribution Shape of Continuous Data SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 369 EP 386 PG 18 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400022 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Equivalence Testing SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 387 EP 396 PG 10 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400023 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Sample Size Required in a Study SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 397 EP 417 PG 21 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400024 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Modeling and Clinical Decisions SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 419 EP 445 PG 27 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400025 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Regression and Correlation Methods SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 447 EP 486 PG 40 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400026 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Survival and Time-Series Analysis SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 487 EP 519 PG 33 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400027 ER PT J AU O'Fallon, WM AF O'Fallon, W. M. (Mike) BA Riffenburgh, RH BF Riffenburgh, RH TI Methods You Might Meet, But Not Every Day SO STATISTICS IN MEDICINE, 2ND EDITION LA English DT Article; Book Chapter C1 [O'Fallon, W. M. (Mike)] Mayo Clin, Rochester, MN 55905 USA. [O'Fallon, W. M. (Mike)] NIH, Study Sect, Bethesda, MD 20892 USA. [O'Fallon, W. M. (Mike)] US FDA, Advisory Comm, Rockville, MD 20857 USA. RP O'Fallon, WM (reprint author), Mayo Clin, Rochester, MN 55905 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 978-0-08-054174-7 PY 2006 BP 521 EP 529 PG 9 WC Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Mathematical & Computational Biology; Medical Informatics; Mathematics GA BCT56 UT WOS:000311359400028 ER PT J AU Yokota, T Kawakami, Y Nagai, Y Ma, JX Tsai, JY Kincade, PW Satob, S AF Yokota, T Kawakami, Y Nagai, Y Ma, JX Tsai, JY Kincade, PW Satob, S TI Bone marrow lacks a transplantable progenitor for smooth muscle type alpha-actin-expressing cells SO STEM CELLS LA English DT Article DE hematopoietic stem cells; stromal cells; transdifferentiation; smooth muscle alpha-actin; transgenic green fluorescent protein mouse ID HEMATOPOIETIC STEM-CELLS; GLOMERULAR MESANGIAL CELLS; STROMAL CELLS; TRANSGENIC MICE; MYELOMONOCYTIC CELLS; ENDOTHELIAL-CELLS; MACROPHAGE FUSION; IN-VITRO; DIFFERENTIATE; TRANSDIFFERENTIATION AB While some studies have suggested that hematopoietic stem cells might give rise to other tissue types, others indicate that transdifferentiation would have to be an extremely rare event. We have now exploited smooth muscle type alpha-actin (alpha SMA) promoter-driven green fluorescent protein (GFP) transgenic mice (alpha SMA-GFP mice) for bone marrow transplantation to evaluate their potential to generate donor-type tissues in irradiation chimeras. There was a highly restricted pattern of GFP expression in the transgenic mice, marking bone marrow stromal cells and mesangial cells in the kidney. However, these characteristics were not transferable to wild-type animals given transgenic marrow cells even though hematopoietic cells were largely replaced. Our findings support earlier studies suggesting that the bone marrow microenvironment is difficult to transplant and indicate that hematopoietic stem cells are unlikely to give rise to alpha SMA-expressing progeny. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73190 USA. NEI, NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. RP Satob, S (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, POB 26901,BSEB 331, Oklahoma City, OK 73190 USA. EM sanai-sato@ouhsc.edu FU NIAID NIH HHS [AI 20069] NR 53 TC 36 Z9 37 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 2006 VL 24 IS 1 BP 13 EP 22 DI 10.1634/stemcells.2004-0346 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 037QR UT WOS:000237162500003 PM 16099999 ER PT J AU Loring, JF Raoh, MS AF Loring, JF Raoh, MS TI Establishing standards for the characterization of human embryonic stem cell lines SO STEM CELLS LA English DT Editorial Material DE human embryonic stein cell; karyotype; characterization; mitochondrial sequencing; methylation AB As of August 2005, 22 human embryonic stem cell (hESC) lines listed on the National Institutes of Health (NIH) hESC Registry were being distributed to investigators. At a June 2005 meeting of NIH-supported hESC researchers, we proposed that a set of shared standards should be available in order to characterize the cells unambiguously in multiple laboratories. Here, we elaborate such a plan to identify a set of standard methods and to initiate collaborative efforts to validate the standards. The standard assays we propose should be comprehensive enough to ensure that hESC banks can provide a consistent and reliable product for NIH researchers, and inexpensive enough that individual laboratories can afford to use at least some of the methods routinely in their laboratories. We expect that as data accumulate and standards evolve, a core set of tests will become the norm for routine assessment of hESC cultures and that these tests will lay the groundwork for clinical applications of these cells. C1 Burnham Inst Med Res, Stem Cell Ctr, La Jolla, CA 92037 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Ctr Gerontol Res, Stem Cell Biol Unit, Lab Neurosci,NIA,NIH, Baltimore, MD 21205 USA. RP Raoh, MS (reprint author), Invitrogen Corp, 1600 Faraday Rd, Carlsbad, CA 92008 USA. EM jloring@burnham.org; mahendra.rao@invitrogen.com NR 0 TC 62 Z9 63 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 2006 VL 24 IS 1 BP 145 EP 150 DI 10.1634/stemcells.2005-0432 PG 6 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 037QR UT WOS:000237162500016 PM 16253979 ER PT S AU Charmandari, E Chrousos, GP AF Charmandari, Evangelia Chrousos, George P. BE Chrousos, GP Tsigos, C TI Metabolic syndrome manifestations in classic congenital adrenal hyperplasia - Do they predispose to atherosclerotic cardiovascular disease and secondary polycystic ovary syndrome? SO STRESS, OBESITY, AND METABOLIC SYNDROME SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Bjorntorp Symposium on Stress, Obesity, and Metabolic Syndrome CY APR 09-10, 2005 CL Athens, GREECE SP Roche Hellas, Abbott Hellas, Pfizer Hellas, Sanofi Aventis Hellas, GlaxoSmithKline Hellas DE congenital adrenal hyperplasia; obesity; impaired adrenomedullary function; hypercortisolism; endothelial dysfunction; atherosclerotic cardiovascular disease ID HUMAN ADRENOCORTICAL-CELLS; INSULIN-RESISTANCE; 21-HYDROXYLASE DEFICIENCY; ENDOTHELIAL DYSFUNCTION; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; STEROIDOGENIC ENZYME; SIGNAL-TRANSDUCTION; NECROSIS-FACTOR; ADIPOSE-TISSUE AB Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired adrenocortical and adrenomedullary function, and adrenal hyperandrogenism. Compared to normal subjects, patients with classic CAH have increased incidence of obesity and visceral adiposity, hyperinsulinism and insulin resistance, hyperleptinemia, hypertension, and hyperandrogenism. It is likely that the impaired adrenomedullary function and intermittent treatment-related hypercortisolism may account for the above abnormalities, and may predispose these subjects to the development of metabolic syndrome-related endothelial dysfunction and atherosclerotic cardiovascular disease in adulthood. Nonpharmacologic and pharmacologic interventions targeting obesity and/or insulin resistance may offer an improved outcome in terms of cardiovascular morbidity. C1 NICHHD, Sect Pediat Endocrinol, Reprod & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Charmandari, E (reprint author), Middlesex Hosp, 3rd Floor Dorville House,Mortimer St, London W1T 8AA, England. EM charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 68 TC 26 Z9 27 U1 0 U2 5 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-625-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1083 BP 37 EP 53 DI 10.1196/annals.1367.005 PG 17 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BFR90 UT WOS:000244102900005 PM 17148732 ER PT S AU Zoumakis, E Rice, KC Gold, PW Chrousos, GP AF Zoumakis, E. Rice, K. C. Gold, P. W. Chrousos, G. P. BE Chrousos, GP Tsigos, C TI Potential uses of corticotropin-releasing hormone antagonists SO STRESS, OBESITY, AND METABOLIC SYNDROME SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Bjorntorp Symposium on Stress, Obesity, and Metabolic Syndrome CY APR 09-10, 2005 CL Athens, GREECE SP Roche Hellas, Abbott Hellas, Pfizer Hellas, Sanofi Aventis Hellas, GlaxoSmithKline Hellas DE CRH; antalarmin ID FACTOR-RECEPTOR SUBTYPE-1; MAST-CELL DEGRANULATION; ANXIETY-LIKE BEHAVIOR; FACTOR CRF; UROCORTIN-III; PERIPHERAL INFLAMMATION; RHEUMATOID-ARTHRITIS; OPIATE WITHDRAWAL; TYPE-1 RECEPTOR; PLACENTAL CLOCK AB Corticotropin-releasing hormone (CRH), its natural homologs urocortins (UCN) 1, 2, and 3, and several types of CRH receptors (R), coordinate the behavioral, endocrine, autonomic, and immune responses to stress. The potential use of CRH antagonists is currently under intense investigation. Selective antagonists have been used experimentally to clarify the role of CRH-related peptides in anxiety and depression, addictive behavior, inflammatory disorders, acute and chronic neurodegeneration, and sleep disorders, as well as preterm labor. C1 Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Choremeion Res Lab, GR-11527 Athens, Greece. NIDDK, Lab Med Chem, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Dept Pediat 1,Choremeion Res Lab, GR-11527 Athens, Greece. EM chrousge@med.uoa.gr; chrousge@med.uoa.gr NR 73 TC 27 Z9 28 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-625-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1083 BP 239 EP 251 DI 10.1196/annals.1367.021 PG 13 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BFR90 UT WOS:000244102900016 PM 17148743 ER PT S AU Vgontzas, AN Bixler, EO Chrousos, GP AF Vgontzas, Alexandros N. Bixler, Edward O. Chrousos, George P. BE Chrousos, GP Tsigos, C TI Obesity-related sleepiness and fatigue - The role of the stress system and cytokines SO STRESS, OBESITY, AND METABOLIC SYNDROME SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Bjorntorp Symposium on Stress, Obesity, and Metabolic Syndrome CY APR 09-10, 2005 CL Athens, GREECE SP Roche Hellas, Abbott Hellas, Pfizer Hellas, Sanofi Aventis Hellas, GlaxoSmithKline Hellas DE obesity; sleepiness; fatigue; stress; cytokines; cortisol ID EXCESSIVE DAYTIME SLEEPINESS; PITUITARY-ADRENAL AXIS; POLYCYSTIC-OVARY-SYNDROME; PRADER-WILLI-SYNDROME; BODY-FAT DISTRIBUTION; YOUNG-ADULTS; INSULIN-RESISTANCE; CHRONIC INSOMNIA; BREATHING DISORDERS; GENERAL-POPULATION AB Obesity has epidemic proportions in Western societies and, because of its significant association with morbidity and mortality, is a major public health issue. Excessive daytime sleepiness (EDS) and fatigue (tiredness without increased sleep propensity)-which have been associated with obesity-have a significant impact on individual wellbeing and public safety. In this article, we review data that challenge the belief that sleep apnea and sleep disruption per se are the primary determinants of obesity-related daytime sleepiness and fatigue. Specifically, it appears that obesity per se is associated with objective and subjective daytime sleepiness compared to normal-weight controls regardless of sleep apnea and sleep loss. Indeed, obese patients without sleep apnea are sleepier compared to nonobese controls whereas within the morbidly obese, those who have high sleep efficiency at night are sleepier than those who have low sleep efficiency. In addition, in recent studies based on large random samples of the general population, the primary determinants of subjective EDS were depression and metabolic disturbances, that is, obesity/diabetes, and not sleep apnea or objective sleep disruption. Furthermore, sleepiness and fatigue are very prevalent in conditions associated with insulin resistance, for instance, the polycystic ovary syndrome (PCOS), independently of sleep apnea or obesity, or in conditions of insufficient physical activity. On the basis of these data, we propose that obesity-related objective daytime sleepiness and fatigue are associated primarily with metabolic and psychological factors and less with sleep apnea and sleep disruption per se. Furthermore, we suggest that objective sleepiness is primarily related to metabolic factors, whereas fatigue appears to be related to psychological distress. Finally, based on data from studies in normal controls and patients with sleep disorders, we propose that the interaction of the hypothalamic-pituitary-adrenal (HPA) axis and proinflammatory cytokines determines the level of sleep/arousal within the 24-h cycle, that is, "hypercortisolemia" plus hypercytokinemia is associated with low sleep efficiency and fatigue, whereas "eucortisolemia" or "hypocortisolemia" plus hypercytokinemia is associated with high sleep efficiency and objective sleepiness. C1 Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. Univ Athens, Sch Med, Unit Endocrinol Metab & Diabet, GR-11527 Athens, Greece. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, H073,500 Univ Dr, Hershey, PA 17033 USA. EM avgontzas@psu.edu NR 82 TC 89 Z9 91 U1 2 U2 13 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-625-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1083 BP 329 EP 344 DI 10.1196/annals.1367.023 PG 16 WC Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Science & Technology - Other Topics GA BFR90 UT WOS:000244102900021 PM 17148748 ER PT J AU Freitag, MH Peila, R Masaki, K Petrovitch, H Ross, GW White, LR Launer, LJ AF Freitag, MH Peila, R Masaki, K Petrovitch, H Ross, GW White, LR Launer, LJ TI Midlife pulse pressure and incidence of dementia - The Honolulu-Asia Aging Study SO STROKE LA English DT Article DE blood pressure; dementia; epidemiology ID CORONARY-HEART-DISEASE; SYSTOLIC BLOOD-PRESSURE; JAPANESE-AMERICAN MEN; ALZHEIMERS-DISEASE; CARDIOVASCULAR RISK; ARTERIAL STIFFNESS; OLDER; HYPERTENSION; MORTALITY; DIAGNOSIS AB Background and Purpose - Previous studies have shown that midlife systolic blood pressure (SBP) predicts late-life cognitive decline and incident dementia. This study explores whether this association is attributable to the pulsatile, ie, pulse pressure (PP), or the nonpulsatile component of blood pressure (BP). Methods - Data are from the Honolulu-Asia Aging Study, a community-based study of Japanese American men. Midlife BP was measured in 1971 to 1974 and dementia assessment was conducted in late-life. The 2505 men who were dementia free in 1991 and had complete follow-up data were re-examined for incident dementia in 1994 to 1996 and 1997 to 1999. Their age ranged from 71 to 93 years. Survival analysis with age as the time scale was performed to estimate the risk (hazard ratio [HR] and 95% CI) for incident dementia associated with mid- and late-life tertiles of PP and mean arterial BP, as well as SBP and diastolic BP categories. Results - Over a mean of 5.1 years of follow-up, 189 cases (7.5%) of incident Alzheimer disease or vascular dementia were identified. After adjustment for cerebrovascular risk factors, dementia was significantly associated with SBP (HR 1.77; 95% CI, 1.10 to 2.84, for SBP >= 140 mm Hg compared with SBP <120 mm Hg), but not with PP tertiles. Limiting the analysis to those never treated with antihypertensives, high levels of all 4 BP components were significantly associated with dementia. In models with 2 BP components, only SBP remained significant in both the total sample and the never-treated subgroup (HR 2.29; 95% CI, 1.23 to 4.25, for SBP >= 140 mm Hg in total sample), whereas PP was not significantly associated with the risk for dementia. Conclusions - Midlife PP is not independently associated with dementia incidence. Midlife SBP is the strongest BP component predicting incident dementia. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Gen Prevent Med Residency Program, Baltimore, MD USA. Univ Bayreuth, Inst Med Management & Gesundheitwissensch, Bayreuth, Germany. Pacific Hlth Res Inst, Honolulu, HI USA. Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI 96817 USA. Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. Dept Vet Affairs, Honolulu, HI USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Room 3C-309 Gateway Bldg,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov RI Freitag, Michael/G-4887-2011 OI Freitag, Michael/0000-0002-7572-2011 FU Intramural NIH HHS; NIA NIH HHS [5 R01 AG017155-04, 1 U01 AG19349-01] NR 32 TC 72 Z9 75 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 33 EP 37 DI 10.1161/01.STR.0000196941.58869.2d PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500013 PM 16339468 ER PT J AU Jiang, B Wang, WZ Chen, HL Hong, Z Yang, QD Wu, SP Du, XL Bao, QJ AF Jiang, B Wang, WZ Chen, HL Hong, Z Yang, QD Wu, SP Du, XL Bao, QJ TI Incidence and trends of stroke and its subtypes in China - Results from three large cities SO STROKE LA English DT Article DE epidemiology; stroke; incidence ID CASE-FATALITY; 1ST-EVER STROKE; PART I; COMMUNITY; EPIDEMIOLOGY; POPULATION; SURVIVAL; REGISTER; PROJECT; RATES AB Background and Purpose - To examine the incidence and trends of stroke and its major subtypes during the 1990s in 3 cities in China. Methods - Stroke cases registered between 1991 to 2000 were initially identified through the stroke surveillance networks established in Beijing, Shanghai, and Changsha, and then confirmed by neurologists. Results - The age-standardized incidence rates per 100 000 person years of overall first-ever stroke were 135.0 (95% CI, 126.5 to 144.6) in Beijing, 76.1 (70.6 to 82.6) in Shanghai, and 150.0 (141.3 to 160.0) in Changsha during the 1990s. Incidence of ischemic stroke (IS) was highest in Beijing, followed by Changsha and Shanghai; for intracerebral hemorrhage (ICH), the highest rate was found in Changsha, followed by Beijing and Shanghai. The same order as ICH was also observed for subarachnoid hemorrhage. The age-adjusted incidence of overall stroke and ICH for individuals >= 55 years of age in our populations was generally higher than that from Western populations. During the 1990s, ICH incidence decreased significantly at a rate of 12.0% per year in Beijing, 4.4% in Shanghai, and 7.7% in Changsha; in contrast, except for Changsha, IS incidence increased in Beijing (5.0% per year) and Shanghai (7.7%). Conclusions - There is a geographic variation in the incidence of stroke and its subtypes among these 3 cities, but the incidence of overall and hemorrhagic stroke in China is generally higher than that in the Western countries. Interestingly, the decrease in ICH and increase in IS during the past decade may reflect some underlying changes of risk factors in Chinese populations. C1 Beijing Neurosurg Inst, Dept Neuroepidemiol, Beijing 100050, Peoples R China. Fudan Univ, Huashan Hosp, Coll Med, Inst Neurol,Dept Neuroepidemiol, Shanghai 200433, Peoples R China. Zhongnan Univ, Xiangya Hosp, MedCol, Inst Neurol,Dep Neuroepidemiol, Changsha, Peoples R China. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. RP Jiang, B (reprint author), Beijing Neurosurg Inst, Dept Neuroepidemiol, 6 Tiantan Xili,Yongnei St, Beijing 100050, Peoples R China. EM bjyjiang@hotmail.com OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS NR 27 TC 156 Z9 188 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 63 EP 68 DI 10.1161/01.STR.0000194955.34820.78 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500018 PM 16306469 ER PT J AU Cooper, LS Wong, TY Klein, R Sharrett, AR Bryan, RN Hubbard, LD Couper, DJ Heiss, G Sorlie, PD AF Cooper, LS Wong, TY Klein, R Sharrett, AR Bryan, RN Hubbard, LD Couper, DJ Heiss, G Sorlie, PD TI Retinal microvascular abnormalities and MRI-defined subclinical cerebral infarction - The atherosclerosis risk in communities study SO STROKE LA English DT Article DE cerebrovascular disorders; cerebral infarction; hypertension; retinal artery; retinal blood vessels; stroke ID SILENT BRAIN INFARCTION; WHITE-MATTER LESIONS; CARDIOVASCULAR HEALTH; ANATOMIC CHARACTERISTICS; GENERAL-POPULATION; CLINICAL STROKE; BLOOD-PRESSURE; RETINOPATHY; DISEASE; PHOTOGRAPHY AB Background and Purpose - Retinal microvascular abnormalities reflect cumulative small vessel damage from elevated blood pressure and may reflect subclinical cerebral microvascular changes. We examined their associations with MRI-defined cerebral infarcts. Methods - Population-based, cross-sectional study of 1684 persons 55 to 74 years of age without a history of clinical stroke, sampled from 2 US southeastern communities. Retinal photographs were obtained and graded for presence of retinal microvascular abnormalities, including arteriovenous nicking, focal arteriolar narrowing, retinal hemorrhages, soft exudates and microaneurysms. Photographs were also digitized, and retinal vessel diameters were measured and summarized as the arteriole-to-venule ratio (AVR). Cerebral MRI scans were graded for presence of cerebral infarct, defined as a lesion >= 3 mm diameter in a vascular distribution with typical imaging characteristics. Results - There were a total of 183 MRI cerebral infarcts. After adjustment for age, gender, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, cerebral infarcts were associated with retinal microvascular abnormalities, with odds ratios 1.90 (95% CI, 1.25 to 2.88) for arteriovenous nicking, 1.89 (95% CI, 1.22 to 2.92) for focal arteriolar narrowing, 2.95 (95% CI, 1.30 to 6.71) for blot hemorrhages, 2.08 (95% CI, 0.69, 6.31) for soft exudates, 3.17 (95% CI, 1.05 to 9.64) for microaneurysms, and 1.74 (95% CI, 0.95 to 3.21) for smallest compared with largest AVR. In stratified analyses, these associations were only present in persons with hypertension. Conclusions - Retinal microvascular abnormalities are associated with MRI-defined subclinical cerebral infarcts independent of stroke risk factors. These data suggest that retinal photography may be useful for studying subclinical cerebrovascular disease in population-based studies. C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. NHLBI, NIH, Bethesda, MD 20892 USA. Natl Univ Singapore, Eye Res Inst, Singapore 117548, Singapore. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Univ Penn, Div Radiol, Philadelphia, PA 19104 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au FU NHLBI NIH HHS [N01 HC-55015, N01 HC-35125, N01 HC-35126, N01 HC-55018, N01 HC-55019, N01 HC-55020, N01 HC-55022, N01-HC-55016, R21-HL077166] NR 25 TC 111 Z9 114 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 82 EP 86 DI 10.1161/01.STR.0000195134.04355.e5 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500021 PM 16306463 ER PT J AU Sawaki, L Wu, CWH Kaelin-Lang, A Cohen, LG AF Sawaki, L Wu, CWH Kaelin-Lang, A Cohen, LG TI Effects of somatosensory stimulation on use-dependent plasticity in chronic stroke SO STROKE LA English DT Article DE nerve stimulation; neuronal plasticity; stroke; stimulation,transcranial magnetic ID MOTOR CORTEX; MODULATION; INPUTS AB Background and Purpose - There is a need to develop strategies to enhance the beneficial effects of motor training, including use-dependent plasticity (UDP), in neurorehabilitation. Peripheral nerve stimulation (PNS) modulates motor cortical excitability in healthy humans and could influence training effects in stroke patients. Methods - We compared the ability of PNS applied to the (1) arm, (2) leg, and (3) idle time to influence training effects in the paretic hand in 7 chronic stroke patients. The end point measure was the magnitude of UDP. Results - UDP was more prominent with arm stimulation (increased by 22.8%) than with idle time (by 2.9%) or leg stimulation (by 6.4%). Conclusions - PNS applied to the paretic limb paired with motor training enhances training effects on cortical plasticity in stroke patients. C1 Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD USA. Wake Forest Univ, Program Rehabil, Dept Neurol, Winston Salem, NC USA. Univ Hosp Inselspital, Motor Lab, Dept Neurol, Bern, Switzerland. Univ Hosp Inselspital, Movement Disorders Ctr, Bern, Switzerland. RP Sawaki, L (reprint author), Sticht Ctr, Program Rehabil, Dept Neurol, Med Ctr Blvd,Ground Floor, Winston Salem, NC 27157 USA. EM lsawaki@wfubmc.edu FU Intramural NIH HHS NR 12 TC 63 Z9 64 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 246 EP 247 DI 10.1161/01.STR.0000195130.16843.ac PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500051 PM 16322491 ER PT J AU Leblanc, GG Meschia, JF Stuss, DT Hachinski, V AF Leblanc, GG Meschia, JF Stuss, DT Hachinski, V TI Genetics of vascular cognitive impairment - The opportunity and the challenges SO STROKE LA English DT Review DE cerebrovascular disorders; cognition; dementia; ischemia ID CEREBRAL AMYLOID ANGIOPATHY; WHITE-MATTER LESIONS; APOLIPOPROTEIN-E GENOTYPE; AUTOSOMAL-DOMINANT ARTERIOPATHY; DIFFERENT DIAGNOSTIC-CRITERIA; SILENT BRAIN INFARCTS; SMOOTH-MUSCLE-CELLS; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE; RISK-FACTORS AB Background and Purpose - This review considers the current state of knowledge of genetic factors underlying vascular cognitive impairment (VCI). Summary of Review - We argue here that genes conferring susceptibility to VCI must be of 2 nonmutually exclusive classes: (1) genes that confer susceptibility to cerebrovascular disease, and (2) genes that determine brain tissue responses to cerebrovascular disease (ie, render parenchymal tissue more or less susceptible to injury or able to repair itself after injury). Although some progress has been made in identifying genes of the first class, little has been done to explore genes of the second class. Evidence for the existence of such genes is presented. We discuss the advantages and disadvantages of different forms of cerebrovascular disease for studying these genes, and different study designs that might be used. Conclusion - The most critical challenge for genetic studies of VCI is to identify quantifiable phenotypes that can be reliably and effectively determined in large samples of subjects. C1 Natl Inst Neurol Disorders & Stroke, Neurogenet Grp, Bethesda, MD 20892 USA. Mayo Clin, Dept Neurol, Jacksonville, FL USA. Univ Toronto, Rotman Res Inst, Baycrest Ctr Geriatr Care, Toronto, ON, Canada. Univ Western Ontario, London Hlth Sci Ctr, London, ON, Canada. RP Leblanc, GG (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Grp, 6001 Execut Blvd,Room 2114, Bethesda, MD 20892 USA. EM leblancg@ninds.nih.gov NR 116 TC 26 Z9 26 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2006 VL 37 IS 1 BP 248 EP 255 DI 10.1161/01.STR.0000195177.61184.49 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996BD UT WOS:000234148500052 PM 16339474 ER PT J AU Aros, S Mills, JL Torres, C Henriquez, C Fuentes, A Capurro, T Mena, M Conley, M Cox, C Signore, C Klebanoff, M Cassorla, F AF Aros, S Mills, JL Torres, C Henriquez, C Fuentes, A Capurro, T Mena, M Conley, M Cox, C Signore, C Klebanoff, M Cassorla, F TI Prospective identification of pregnant women drinking four or more standard drinks (>= 48 g) of alcohol per day SO SUBSTANCE USE & MISUSE LA English DT Article DE fetal alcohol syndrome; screening; alcohol; pregnancy; alcoholism; risk ID CONSUMPTION; EXPOSURE AB We aimed to identify drinking rates in a prospectively identified cohort of pregnant women, and subsequently, to identify the drinkers of 48 g or more alcohol/day among them, by using complementary methods for verifying self/reported drinking habits. A research team of social workers and health professionals at the Maipu Clinic, located in a lower middle class neighborhood of Santiago, Chile, conducted interviews of women attending a prenatal clinic between August 1995 and July 2000. Women whose interview responses met predefined criteria (identified in the text) were further evaluated by home visits. We interviewed 9,628 of 10,917 (88%) women receiving prenatal care. By initial interview, 42.6% of women reported no drinking, 57.4% some alcohol consumption, and 3.7% consuming at least one standard drink (15 mL of absolute alcohol) per day. Of the 887 women who had home visits, 101 were identified as consuming on average at least 4 drinks/day (48 g). To determine the best home visit questionnaire items for identifying those drinking at least 4 drinks per day, 48 women who openly admitted drinking this amount were compared with 786 women who were not considered drinkers after the home visit. The 48 self-reported 48 g/day drinkers were significantly more likely to get tipsy when drinking before (p = 0.01) or during (p < 0.0001) pregnancy, to have started drinking at a younger age (p = 0.007), or to exhibit signs of low self-esteem (p < 0.0001), sleep or appetite problems (p < 0.0001), bad interpersonal relationships (p < 0.0001) or having family members with fetal alcohol syndrome features (p < 0.009). In conclusion, using complementary methods of alcohol misuse ascertainment during pregnancy, we found that at least 1% of pregnant women in a Santiago, Chile, clinic population were drinking at levels that are clearly dangerous to the fetus (48 g/day or more). We identified specific interview questions that may help screen for alcohol use of 48 g/day or more in pregnant women. C1 NICHD, DHHS, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Univ Chile, Dept Pediat, Sch Med, Hosp San Borja Arriaran, Santiago, Chile. Univ Chile, Inst Invest Materno Infantil, Sch Med, Santiago, Chile. RP Mills, JL (reprint author), NICHD, DHHS, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov FU Intramural NIH HHS NR 15 TC 11 Z9 12 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2006 VL 41 IS 2 BP 183 EP 197 DI 10.1080/10826080500391779 PG 15 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 012MM UT WOS:000235343300003 PM 16479683 ER PT J AU Bryant, KJ AF Bryant, Kendall J. TI Expanding research on the role of alcohol consumption and related risks in the prevention and treatment of HIV/AIDS SO SUBSTANCE USE & MISUSE LA English DT Review DE AIDS; alcohol consumption; alcohol misuse; at risk; behavior; CNS; HIV; immune ID SUBSTANCE-ABUSE TREATMENT; CENTRAL-NERVOUS-SYSTEM; HIV-INFECTED PATIENTS; INJECTING DRUG-USERS; IMMUNODEFICIENCY-VIRUS-INFECTION; SEXUALLY-TRANSMITTED INFECTIONS; INCREASING COGNITIVE IMPAIRMENT; ACTIVE ANTIRETROVIRAL THERAPY; PRIMARY SOCIALIZATION THEORY; USE DISORDERS AB This article is a review of some of the major epidemiological, behavioral, biological, and integrative prevention research issues and priorities in the area of HIV_AIDS and alcohol consumption. Drinking alcohol increases both the risk for infection with HIV and related illnesses and the morbidity and mortality of patients who progress to AIDS. New and improved measurement procedures have helped in assessment of the complex patterns of alcohol use, identification of intervening explanatory mechanisms for risk behaviors and contexts, and determination of intervention outcomes. Both the direct and indirect effects of alcohol misuse appear to be major contributors to both the risk for infection with HIV and the transmission of HIV_AIDS at the individual and population levels. There is increasing evidence that perhaps no level of alcohol consumption is "safe" for those who are HIV infected and receiving antiretroviral treatment. Interdisciplinary basic behavioral and biomedical research is needed to develop comprehensive culturally appropriate strategies for programs that can be effectively delivered in community contexts in the United States and abroad and that focus on the integration of our understanding of individual behaviors, high-risk group membership, biological mechanisms, and the social and physical environments that place individuals at risk for HIV infection. High-priority topics include improving adherence to antiretroviral medications, prevention of infection in young minority women in the United States, and treatment of HIV+ pregnant women who are alcohol abusers to prevent adverse fetal outcomes, which is an international focus in under-resourced settings in Africa. C1 NIAAA, Rockville, MD 20852 USA. RP Bryant, KJ (reprint author), NIAAA, 5635 Fishers Lane, Rockville, MD 20852 USA. EM kbryant@mail.nih.gov NR 257 TC 64 Z9 65 U1 4 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2006 VL 41 IS 10-12 BP 1465 EP 1507 DI 10.1080/10826080600846250 PG 43 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 087ZQ UT WOS:000240781700005 PM 17002990 ER PT J AU Wallace, DJ Altemare, CR Shen, DF deSmet, MD Buggage, RR Nussenblatt, RB Chan, CC AF Wallace, DJ Altemare, CR Shen, DF deSmet, MD Buggage, RR Nussenblatt, RB Chan, CC TI Primary testicular and intraocular lymphomas: Two case reports and a review of the literature SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE immune privileged organ; immunohistochemistry; intraocular lymphoma; microdissection; PCR; retina; testicular lymphoma; vitreous ID NERVOUS-SYSTEM LYMPHOMA; RETICULUM-CELL SARCOMA; NON-HODGKINS LYMPHOMA; PRIMARY CNS LYMPHOMA; T(14-18) CHROMOSOMAL TRANSLOCATION; POLYMERASE-CHAIN-REACTION; MALIGNANT-LYMPHOMA; CLINICAL-FEATURES; INTRAVITREAL METHOTREXATE; TESTIS AB Testicular lymphoma is a rare neoplasm of the testis that is most commonly seen in older patients. It metastasizes preferentially to extranodal sites, including the skin, central nervous system, Waldeyer ring, contralateral testis, and lung. Two case reports of patients with a history of testicular lymphoma who developed involvement of the vitreous and retina are presented. These are interesting cases as the testis, central nervous system, and eye are all immune privileged organs, which may account for occurrence of disease in these sites. Histopathologic examination of diagnostic vitrectomy specimens from both cases showed atypical lymphoid cells with immunoglobulin heavy chain (IgH) gene rearrangements, consistent with the diagnosis of intraocular B-cell lymphoma. The results of a literature review of all reports of ocular involvement with testicular lymphoma are discussed. Patients with testicular lymphoma are at risk for relapse, particularly in the central nervous system. Clinicians should be suspicious for intraocular lymphoma in patients with a history of testicular lymphoma who present with vitritis or retinal lesions. (C) 2006 Elsevier Inc. All rights reserved. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Chan, CC (reprint author), NEI, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 74 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JAN-FEB PY 2006 VL 51 IS 1 BP 41 EP 50 DI 10.1016/j.survophthal.2005.11.002 PG 10 WC Ophthalmology SC Ophthalmology GA 004OQ UT WOS:000234762500003 PM 16414360 ER PT J AU Li, XJ AF Li, XJ TI Condition-directable reaction: Regio- and stereoselective elimination of 2,3-dibromo-2-methylpropyl phenyl sulfone via base-solvent selection SO SYNTHETIC COMMUNICATIONS LA English DT Article DE diversity-oriented; reaction condition-directable; regio- and stereoselective; elimination; vinyl sulfones; vinyl bromides; dibromo; phenyl sulfone ID CROSS-COUPLING REACTIONS; ALLYL SULFONES; ELECTROPHILES AB Diversity-oriented organic synthesis is an important approach for combinatorial chemistry and drug discovery. An example of this approach is selective elimination of 2,3-dibromo-2-methylpropyl phenyl sulfone 5 to potentially useful vinyl sulfones 6 E/Z and vinyl bromides 7 E/Z , which is achieved by choosing reaction conditions. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Li, XJ (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr,Twinbrook 2, Rockville, MD 20852 USA. EM lixi@niaid.nih.gov NR 22 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 2006 VL 36 IS 3 BP 393 EP 399 DI 10.1080/00397910500377552 PG 7 WC Chemistry, Organic SC Chemistry GA 005JT UT WOS:000234819100015 ER PT S AU Sostaric, JZ Miyoshi, N Riesz, P De Graff, WG Mitchell, JB AF Sostaric, Joe Z. Miyoshi, Norio Riesz, Peter De Graff, William G. Mitchell, James B. BE Clement, GT McDannold, NJ Hynynen, K TI Complete inhibition of ultrasound induced cytolysis in the presence of inertial cavitation SO THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE cavitation; Surfactants; sonoprotection; glucopyranoside; leukemia; HL-60 ID IN-VITRO; SONOCHEMISTRY; SURFACTANTS AB The investigation of ultrasound for biotechnological applications including noninvasive surgery (HIFU), drug/gene delivery to cells (sonoporation) or through the skin (sonophoresis) and ultrasound assisted bioreactors has focused mainly on the physical effects of ultrasound. The beneficial effects of ultrasound rely on a number of application-dependent mechanisms, and may include tissue heating, acoustic streaming or cavitation. Although acoustic cavitation is necessary in some systems, cavitation bubbles simultaneously result in uncontrollable cell damage and cytolysis. Thus, the development of a number of biotechnological uses of ultrasound has been hampered by the necessity to constrain exposure parameters in order to prevent the occurrence of acoustic cavitation or to at least limit the detrimental effects of cavitation. The current study shows that non-toxic concentrations of specific n-alkyl solutes completely inhibit ultrasound induced cytolysis of in vitro suspensions of human leukemia cells (HL-60). Protection of the whole cell population from cytolysis is achieved even under extreme ultrasound exposure conditions that result in cytolysis of 100% of the cell population in the absence of the n-alkyl solutes. Furthermore, the n-alkyl solutes did not hinder the process of inertial cavitation. This method may allow utilization of beneficial effects of ultrasound and cavitation while protecting cells from cavitation induced cytolysis and thereby presents new possibilities for ultrasound in medicine and biology. C1 [Sostaric, Joe Z.] Ohio State Univ, Ctr Biomed EPR Imaging, Davis Heart & Lung Res Inst, 420 W 12th Ave,TMRF-184, Columbus, OH 43210 USA. [Sostaric, Joe Z.; Miyoshi, Norio; Riesz, Peter; De Graff, William G.; Mitchell, James B.] NCI, NIH, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. [Miyoshi, Norio] Univ Fukui, Fac Med, Dept Pathol Sci, Div Tumor Pathol, Fukui 9101193, Japan. RP Sostaric, JZ (reprint author), Ohio State Univ, Ctr Biomed EPR Imaging, Davis Heart & Lung Res Inst, 420 W 12th Ave,TMRF-184, Columbus, OH 43210 USA. FU National Cancer Institute FX Joe Z. Sostaric acknowledges a Visiting Fellowship from the Fogarty International Center, NIH. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 15 TC 1 Z9 1 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 39 EP + PG 2 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700008 ER PT S AU Wood, BJ Yanof, J Frenkel, V Viswanathan, A Dromi, S Oh, K Kruecker, J Bauer, C Seip, R Kam, A Li, KCP AF Wood, Bradford J. Yanof, J. Frenkel, V. Viswanathan, A. Dromi, S. Oh, K. Kruecker, J. Bauer, C. Seip, R. Kam, A. Li, K. C. P. BE Clement, GT McDannold, NJ Hynynen, K TI CT and ultrasound guided stereotactic high intensity focused ultrasound (HIFU) SO THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE CT intervention; image guided therapy; pulsed-HIFU; drug delivery ID MODEL AB To demonstrate the feasibility of CT and B-mode Ultrasound (US) targeted HIFU, a prototype coaxial focused ultrasound transducer was registered and integrated to a CT scanner. CT and diagnostic ultrasound were used for HIFU targeting and monitoring, with the goals of both thermal ablation and non-thermal enhanced drug delivery. A 1 megahertz coaxial ultrasound transducer was custom fabricated and attached to a passive position-sensing arm and an active six degree-of-freedom. robotic arm via a CT stereotactic frame. The outer therapeutic transducer with a 10 cm fixed focal zone was coaxially mounted to an inner diagnostic US transducer (2-4 megahertz, Philips Medical Systems). This coaxial US transducer was connected to a modified commercial focused ultrasound generator (Focus Surgery, Indianapolis, IN) with a maximum total acoustic power of 100 watts. This pre-clinical paradigm was tested for ability to heat tissue in phantoms with monitoring and navigation from CT and live US. The feasibility of navigation via image fusion of CT with other modalities such as PET and MRI was demonstrated. Heated water phantoms were tested for correlation between CT numbers and temperature (for ablation monitoring). The prototype transducer and integrated CT/US imaging system enabled simultaneous multimodality imaging and therapy. Pre-clinical phantom models validated the treatment paradigm and demonstrated integrated multimodality guidance and treatment monitoring. Temperature changes during phantom cooling corresponded to CT number changes. Contrast enhanced or non-enhanced CT numbers may potentially be used to monitor thermal ablation with HIFU. Integrated CT, diagnostic US, and therapeutic focused ultrasound bridges a gap between diagnosis and therapy. Preliminary results show that the multimodality system may represent a relatively inexpensive, accessible, and simple method of both targeting and monitoring HIFU effects. Small animal pre-clinical models may be translated to large animals and humans for HIFU-induced ablation and drug delivery. Integrated CT-guided focused ultrasound holds promise for tissue ablation, enhancing local drug delivery, and CT thermometry for monitoring ablation in near real-time. C1 [Wood, Bradford J.; Frenkel, V.; Viswanathan, A.; Dromi, S.; Oh, K.; Kam, A.; Li, K. C. P.] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Yanof, J.; Bauer, C.] Computed Tomog Clin Sci Dept, Philips Med Syst, Cleveland, OH USA. [Kruecker, J.] Philips Res Labs, Clin Res Program, Briarcliff Manor, NY USA. RP Wood, BJ (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. OI Viswanathan, Anand/0000-0003-3810-6217 FU Intramural Research Training Program of the NIH Clinical Center FX The authors would like to thank Julie Locklin, MS RN for editing, and Alia Durrani for water bolus design. The research presented here was supported, in part, by the Intramural Research Training Program of the NIH Clinical Center. NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 122 EP + PG 2 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700024 ER PT S AU Sostaric, JZ Miyoshi, N Riesz, P De Graff, WG Mitchell, JB AF Sostaric, Joe Z. Miyoshi, Norio Riesz, Peter De Graff, William G. Mitchell, James B. BE Clement, GT McDannold, NJ Hynynen, K TI Complete inhibition of ultrasound induced cytolysis in the presence of inertial cavitation SO THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE cavitation; Surfactants; sonoprotection; glucopyranosidc; leukemia; HL-60 ID IN-VITRO; SONOCHEMISTRY; SURFACTANTS AB The investigation of ultrasound for biotechnological applications including non-invasive surgery (HIM), drug/gene delivery to cells (sonoporation) or through the skin (sonophoresis) and ultrasound assisted bioreactors has focused mainly on the physical effects of ultrasound. The beneficial effects of ultrasound rely on a number of application-dependent mechanisms, and may include tissue heating, acoustic streaming or cavitation. Although acoustic cavitation is necessary in some systems, cavitation bubbles simultaneously result in uncontrollable cell damage and cytolysis. Thus, the development of a number of biotechnological uses of ultrasound has been hampered by the necessity to constrain exposure parameters in order to prevent the occurrence of acoustic cavitation or to at least limit the detrimental effects of cavitation. The current study shows that non-toxic concentrations of specific n-alkyl solutes completely inhibit ultrasound induced cytolysis of in vitro suspensions of human leukemia cells (HL-60). Protection of the whole cell population from cytolysis is achieved even under extreme ultrasound exposure conditions that result in cytolysis of 100% of the cell population in the absence of the n-alkyl solutes. Furthermore, the n-alkyl solutes did not hinder the process of inertial cavitation. This method may allow utilization of beneficial effects of ultrasound and cavitation while protecting cells from cavitation induced cytolysis and thereby presents new possibilities for ultrasound in medicine and biology. C1 [Sostaric, Joe Z.; Miyoshi, Norio; Riesz, Peter; De Graff, William G.; Mitchell, James B.] NCI, NIH, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. [Miyoshi, Norio] Univ Fukui, Fac Med, Dept Pathol Sci, Div Tumor Pathol, Fukui 9101193, Japan. [Sostaric, Joe Z.] Ohio State Univ, Ctr Biomed EPR Imaging, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. RP Sostaric, JZ (reprint author), NCI, NIH, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. FU Intramural Research Program; NIH; National Cancer Institute; Center for Cancer Research FX This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 15 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 283 EP + PG 2 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700056 ER PT S AU Frenkel, V Deng, C O'Neill, BE Quijano, J Stone, MJ Dromi, S Hunter, F Xie, JW Quinn, TP Wood, BJ Li, KCP AF Frenkel, Victor Deng, Cheri O'Neill, Brian E. Quijano, Jade Stone, Michael J. Dromi, Sergio Hunter, Finie Xie, Jianwu Quinn, Timothy P. Wood, Bradford J. Li, King C. P. BE Clement, GT McDannold, NJ Hynynen, K TI Pulsed-high intensity focused ultrasound (HIFU) exposures for enhanced delivery of therapeutics: Mechanisms and applications SO THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE pulsed-HIFU; radiation forces; tissue displacement; enhanced delivery ID THERAPY; TUMORS; TRANSPORT; MODEL AB The majority of focused ultrasound applications today involve long, continuous exposures that produce significant temperature elevations for tissue ablation and irreversible coagulative necrosis. Comparatively little has been done with non-continuous (or, pulsed) exposures that can produce primarily mechanical effects with only minimal heat. Our investigations have shown that pulsed-HIFU exposures can non-invasively and non-destructively enhance the delivery of both systemically and locally injected materials (e.g. imaging agents, optical probes, and plasmid DNA) in both normal and cancerous tissues. It is hypothesized that the enhancing effects are directly linked to tissue displacement from locally-generated radiation forces. In normal tissue, it is thought that shear forces are produced between adjacent tissue regions experiencing non-uniform displacement. The resulting strain opens cellular junctions in both the vasculature and the parenchyma, increasing extravasation and interstitial diffusion, respectively. In solid tumors, improved delivery is thought to also be related to both an increase in fluid exchange that leads to decreased interstitial pressure, and disruptions of fibrillar collagen in the extracellular matrix. Preliminary experiments are presented that were carried out to help elucidate the mechanisms by which enhanced delivery was achieved, and possible directions for future investigations are discussed. C1 [Frenkel, Victor; Quijano, Jade; Stone, Michael J.; Dromi, Sergio; Hunter, Finie; Xie, Jianwu; Wood, Bradford J.; Li, King C. P.] Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Deng, Cheri] Case Western Reserve Univ, Dept Biomed Engn & Radiol, Cleveland, OH 44106 USA. [O'Neill, Brian E.; Quinn, Timothy P.] Natl Inst Stand & Technol, Boulder, CO 80303 USA. RP Frenkel, V (reprint author), Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. FU Intramural Research Training Program of the NIH Clinical Center FX The authors would like to thank Mr. Jason A. Poff for editing this abstract. The research presented here was supported, in part, by the Intramural Research Training Program of the NIH Clinical Center. NR 17 TC 1 Z9 1 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 528 EP + PG 2 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700104 ER PT S AU Kam, AW Wang, HH Thomasson, D Farahani, K Li, KCP AF Kam, Anthony W. Wang, Honghui Thomasson, David Farahani, Keyvan Li, King C. P. BE Clement, GT McDannold, NJ Hynynen, K TI Characterization of pulsed high intensity focused ultrasound for enhanced drug and gene delivery SO THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th International Symposium on Therapeutic Ultrasound CY OCT 27-29, 2005 CL Boston, MA SP Int Soc Therapeut Ultrasound, Acout Soc Amer, Fdn Focused Ultrasound Res DE focused ultrasound; MR thermometry; drug and gene delivery ID MODEL AB Within a certain range of parameters, pulsed high intensity focused ultrasound (HIFU) has been shown to increase the delivery of systemically administered drugs and plasmid DNA in tumors in mice. The sonicated tissue is not damaged by light microscopy. The mechanism for the enhanced delivery has not been shown conclusively and can include thermal, cavitational, and non-cavitation mechanical effects. In order to assess the effects of pulsed HIFU in a manner that allows for clinical translation, pulsed HIFU is performed within a magnetic resonance (MR) scanner. In this works the thermal effect is evaluated with phase-shift MR thermometry in ex vivo chicken muscle. The thermal effect is small at the most common exposure parameters. In the future, non-thermal effects like permeability, diffusion, and elasticity changes will be evaluated with dynamic contrast enhanced MRI, diffusion-weighted MRI, and MR elastography. If changes in permeability, diffusion, and shear modulus are associated with pulsed HIFU enhanced delivery, then these parameters can be used as markers for optimization of pulsed HIFU enhanced delivery. C1 [Kam, Anthony W.; Wang, Honghui; Thomasson, David; Li, King C. P.] NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Kam, Anthony W.] Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD USA. [Farahani, Keyvan] Natl Canc Inst, Rockville, MD USA. RP Kam, AW (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. FU Intramural Research Program; Clinical Center of the NIH FX This work was supported by the Intramural Research Program and the Clinical Center of the NIH. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0321-X J9 AIP CONF PROC PY 2006 VL 829 BP 563 EP + PG 2 WC Acoustics; Biophysics; Medicine, General & Internal SC Acoustics; Biophysics; General & Internal Medicine GA BEN61 UT WOS:000238329700111 ER PT J AU Yende, S Waterer, GW Tolley, EA Newman, AB Bauer, DC Taaffe, DR Jensen, R Crapo, R Rubin, S Nevitt, M Simonsick, EM Satterfield, S Harris, T Kritchevsky, SB AF Yende, S Waterer, GW Tolley, EA Newman, AB Bauer, DC Taaffe, DR Jensen, R Crapo, R Rubin, S Nevitt, M Simonsick, EM Satterfield, S Harris, T Kritchevsky, SB TI Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects SO THORAX LA English DT Article ID NECROSIS-FACTOR-ALPHA; CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; PULMONARY-DISEASE; SKELETAL-MUSCLE; SYSTEMIC INFLAMMATION; BODY-COMPOSITION; COPD PATIENTS; HEALTH ABC; RISK AB Background: Inflammatory markers are increased in chronic obstructive pulmonary disease ( COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition ( Health ABC) study is a prospective observational cohort of well functioning individuals aged 70 - 79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease ( OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p< 0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p< 0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p< 0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 ( adjusted regression coefficients (beta) = -5.3 (95% CI -9.1 to -1.5) and -3.1 (95% CI -4.3 to -1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (beta = -6.4 (95% CI -12.8 to -0.03) and -3.4 (95% CI -5.4 to -1.3), respectively, for IL-6 and beta = -10.1 (95% CI -18.7 to -1.5) and -3.8 (95% CI -7 to -0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity. C1 Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15238 USA. Univ Western Australia, Dept Med, Perth, WA 6009, Australia. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Queensland, Sch Human Movement Studies, St Lucia, Qld 4067, Australia. LDS Hosp, Div Pulm, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. RP Yende, S (reprint author), Univ Pittsburgh, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA 15238 USA. EM yendes@upmc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [R01-HL-074104]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 36 TC 141 Z9 144 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD JAN PY 2006 VL 61 IS 1 BP 10 EP 16 DI 10.1136/thx.2004.034181 PG 7 WC Respiratory System SC Respiratory System GA 999WY UT WOS:000234423000005 PM 16284220 ER PT J AU Bagorda, A Mihaylov, VA Parent, CA AF Bagorda, A Mihaylov, VA Parent, CA TI Chemotaxis: moving forward and holding on to the past SO THROMBOSIS AND HAEMOSTASIS LA English DT Review DE dictyostelium; neutrophils; chemotactic signaling ID NUCLEOTIDE EXCHANGE FACTOR; PLECKSTRIN HOMOLOGY DOMAIN; PROTEIN-COUPLED RECEPTORS; GREEN-FLUORESCENT PROTEIN; DIRECTIONAL CELL-MOVEMENT; HETEROTRIMERIC G-PROTEINS; PHOSPHOLIPASE-C ACTIVITY; CYCLIC ADP-RIBOSE; DICTYOSTELIUM-DISCOIDEUM; CHEMOATTRACTANT RECEPTOR AB The ability of cells to sense external chemical cues and respond by directionally migrating towards them is a fundamental process called chemotaxis. This phenomenon is essential for many biological responses in the human body, including the invasion of neutrophils to sites of inflammation. Remarkably, many of the molecular mechanisms involved in controlling neutrophils chemotaxis arose millions of years ago in the simple eukaryotic organism Dictyostelium discoideum. Both neutrophils and Dictyostelium use G protein-coupled signaling cascades to mediate chemotactic responses, which are responsible for transducing external cues into highly organized cytoskeletal rearrangements that ultimately lead to directed migration. By using the genetically and biochemically tractable organism Dictyostelium as a model system, it has been possible to decipher many of the signal transduction events that are involved in chemotaxis. C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Med Univ Sofia, Lab Mol Biol & Genet, Sofia, Bulgaria. RP NCI, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Room 2066, Bethesda, MD 20892 USA. EM parentc@helix.nih.gov NR 114 TC 51 Z9 54 U1 2 U2 8 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JAN PY 2006 VL 95 IS 1 BP 12 EP 21 DI 10.1160/TH05-07-0483 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 003PC UT WOS:000234693100004 PM 16543956 ER PT J AU Lewis, DA Nyska, A Potti, A Hoke, HA Klemp, KF Ward, SM Peddada, SD Wu, JG Ortel, TL AF Lewis, Deborah A. Nyska, Abraham Potti, Anil Hoke, Heather A. Klemp, Keith F. Ward, Sandra M. Peddada, Shyamal D. Wu, Jogin Ortel, Thomas L. TI Hemostatic activation in a chemically induced rat model of severe hemolysis and thrombosis SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-of-Toxicology CY MAR 06-10, 2005 CL New Orleans, LA SP Soc Toxicol DE animal models; 2-butoxyethanol; hemolysis; microvascular thrombosis; sickle cell disease ID SICKLE-CELL-DISEASE; FEMALE F344 RATS; INHALATION EXPOSURE; COAGULATION CHANGES; NITRIC-OXIDE; 2-BUTOXYETHANOL; HYDROXYUREA; FIBRINOLYSIS; THALASSEMIA; INFARCTION AB Introduction: In hemolytic diseases such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood, however erythrocyte/endothelium interactions are thought to play an important role. Appropriate animal models would increase our understanding of the pathophysiology of thrombosis and aid in the development of new therapeutic strategies. We previously reported that rats exposed to 2-butoxyethanol (2-BE) develop hemolysis and enhanced adherence of erythrocytes to the extracellular matrix, possibly secondary to the recruitment of cellular adhesion molecules at the erythrocyte/endothelium interface. Methods: We exposed rats to 250 mg/kg/day of 2-BE for 4 days, and collected blood for coagulation markers on each day. Results: As previously observed, erythrocytes dropped precipitously (8.0 to 1.8 x 10(6)/mu l in 48 h), and diffuse microvascular thrombosis developed in the heart, lungs, liver, bones and eyes. Prothrombin times, activated partial thromboplastin times, fibrinogen, and antithrombin-III were unchanged between treated and control rats, indicating that hemostasis is largely unperturbed. However the thrombin-antithrombin III levels in the 2-BE treated rats for all days were 3-7 times greater than the control rats. The plasma intercellular adhesion motecule-1 (ICAM-1) levels of 2-BE treated animals were approximately twice that of the controls on days 2 and 3 and 1.5 times the controls on day 4 (P < 0.05). Conclusion: Our findings are consistent with the observations of increased erythrocyte aggregation, increased erythrocyte/endothetium interaction, and increased plasma ICAM-1 Levels observed in sickle cell disease and beta-thatassemia patients. This model may be useful for studying therapeutic agents that disrupt erythrocyte/endothetium interactions. (c) 2005 Elsevier Ltd. All rights reserved. C1 Duke Univ, Med Ctr, Dept Med, Hemostasis & Thrombosis Ctr,Hlth Syst, Durham, NC 27710 USA. NIEHS, Dept Biostat, Res Triangle Pk, NC 27709 USA. RP Lewis, DA (reprint author), Duke Univ, Med Ctr, Dept Med, Hemostasis & Thrombosis Ctr,Hlth Syst, Box 3422, Durham, NC 27710 USA. EM Lewis064@mc.duke.edu RI Peddada, Shyamal/D-1278-2012 NR 33 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2006 VL 118 IS 6 BP 747 EP 753 DI 10.1016/j.thromres.2005.11.010 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 112VQ UT WOS:000242556200013 PM 16405975 ER PT J AU Glicksohn, J Myslobodsky, MS AF Glicksohn, Joseph Myslobodsky, Michael S. BE Glicksohn, J Myslobodsky, MS TI What it Takes to Remember the Future SO TIMING THE FUTURE: THE CASE FOR A TIME-BASED PROSPECTIVE MEMORY LA English DT Article; Book Chapter ID SUBJECTIVE TIME-ESTIMATION; STRATEGY APPLICATION DISORDER; POSTERIOR PARIETAL CORTEX; ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; PROSPECTIVE MEMORY; PREFRONTAL CORTEX; INTERNAL CLOCK; FRONTAL LOBES; WORKING-MEMORY C1 [Glicksohn, Joseph] Bar Ilan Univ, Leslie & Susan Gonda Goldschmied Multidisciplinar, IL-52900 Ramat Gan, Israel. [Glicksohn, Joseph] Bar Ilan Univ, Dept Criminol, IL-52900 Ramat Gan, Israel. [Myslobodsky, Michael S.] Tel Aviv Univ, Tel Aviv, Israel. [Myslobodsky, Michael S.] Howard Univ, Washington, DC 20059 USA. [Myslobodsky, Michael S.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Glicksohn, J (reprint author), Bar Ilan Univ, Leslie & Susan Gonda Goldschmied Multidisciplinar, IL-52900 Ramat Gan, Israel. EM chanita@bgumail.bgu.ac.il; myslobom@mail.nih.gov; chanita@bgumail.bgu.ac.il; myslobom@mail.nih.gov OI Glicksohn, Joseph/0000-0001-5584-177X NR 203 TC 4 Z9 5 U1 2 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-270-712-3 PY 2006 BP 263 EP 306 DI 10.1142/9789812707123_0011 PG 44 WC Psychology, Clinical; Criminology & Penology; Clinical Neurology SC Psychology; Criminology & Penology; Neurosciences & Neurology GA BZF29 UT WOS:000301352100012 ER PT J AU Torimiro, JN Carr, JK Wolfe, ND Karacki, P Martin, MP Gao, X Tamoufe, U Thomas, A Ngole, EM Birx, DL McCutchan, FE Burke, DS Carrington, M AF Torimiro, JN Carr, JK Wolfe, ND Karacki, P Martin, MP Gao, X Tamoufe, U Thomas, A Ngole, EM Birx, DL McCutchan, FE Burke, DS Carrington, M TI HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A*2612-B*4407 haplotype SO TISSUE ANTIGENS LA English DT Article DE allele frequency; Cameroon; haplotype frequency; heterozygosity; locus; polymorphic; population ID AFRICAN POPULATIONS; B ALLELES; C ALLELES; POLYMORPHISM; GENES; LOCI; MITOCHONDRIAL; RECOGNITION; DIMORPHISM; MOLECULES AB The population distribution of alleles of the classical HLA class 1 loci in Cameroon has not been well studied but is of particular interest given the AIDS and malarial epidemics afflicting this population. We investigated the genetic diversity of HLA-A, HLA-B and HLA-C alleles in remote populations of Cameroon. Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA-A, HLA-B and HLA-C alleles using a polymerase chain reaction/sequence-specific oligonucleotide probe assay and sequence analysis. Multiple alleles of the HLA-A (N = 28), HLA-B (N = 41) and HLA-C (N = 21) loci were identified, of which A*2301 [allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles. Twenty-six (28.9%) alleles with a frequency of less than 1% (AF < 1%), 39 (43%) with a frequency of 2.0-15.0% (AF = 2.0-15.0%), three globally uncommon alleles [A*2612 (AF = 2.0%), B*4016 (AF = 0.7%) and B*4407 (AF = 1.4%)], and the 4*2612-Cw*0701/06/18-B*4407 haplotype (haplotype frequency = 1.3%) were also identified. Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA-A, HLA-B and HLA-C, respectively. The extensive allelic and haplotypic diversity observed in this population may have resulted from varied natural selective pressures on the population, as well as intermingling of peoples from multiple origins. Thus, from an anthropologic perspective, these data highlight the challenges in T-cell-based vaccine development, the identification of allogeneic transplant donors and the understanding of infectious disease patterns in different populations. C1 Water Reed Johns Hopkins Cameroon Program, Yaounde, Cameroon. Henry M Jackson Fdn, Rockville, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. SAIC Frederick Inc, Basic Res Program, Lab Genom Divers, Natl Canc Inst, Frederick, MD USA. London Sch Hyg & Trop Med, London WC1, England. Mil Hlth Res Ctr, Yaounde, Cameroon. Walter Reed Army Inst Res, Rockville, MD USA. RP Torimiro, JN (reprint author), Water Reed Johns Hopkins Cameroon Program, BP 7039, Yaounde, Cameroon. EM jtorimro@hopkinscameroon.org OI /0000-0002-5704-8094 FU NCI NIH HHS [N01-CO-12400] NR 30 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JAN PY 2006 VL 67 IS 1 BP 30 EP 37 DI 10.1111/j.1399-0039.2005.00527.x PG 8 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 008IY UT WOS:000235035200003 PM 16451198 ER PT J AU McAllister, KA Houle, CD Malphurs, J Ward, T Collins, NK Gersch, W Wharey, L Seely, JC Betz, L Bennett, LM Wiseman, RW Davis, BJ AF McAllister, KA Houle, CD Malphurs, J Ward, T Collins, NK Gersch, W Wharey, L Seely, JC Betz, L Bennett, LM Wiseman, RW Davis, BJ TI Spontaneous and irradiation-induced tumor susceptibility in brca2 germline mutant mice and cooperative effects with a p53 germline mutation SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Brca2; p53; irradiation; mice; Fanconi anemia ID BREAST-CANCER; IONIZING-RADIATION; FANCONI-ANEMIA; INCREASED CARCINOGENICITY; CHROMOSOMAL INSTABILITY; P53-DEFICIENT MICE; CELL-CYCLE; IN-VIVO; TUMORIGENESIS; APOPTOSIS AB Mutations in both p53 and BRCA2 are commonly seen together in human tumors suggesting that the loss of both genes enhances tumor development. To elucidate this interaction in an animal model, mice lacking the carboxy terminal domain of Brca2 were crossed with p53 heterozygous mice. Females from this intercross were then irradiated with an acute dose of 5 Gy ionizing radiation at 5 weeks of age and compared to nonirradiated controls. We found decreased survival and timing of tumor onsets, and significantly higher overall tumor incidences and prevalence of particular tumors, including stomach tumors and squamous cell carcinomas, associated with the homozygous loss of Brca2, independent of p53 status. The addition of a p53 mutation had a further impact on overall survival, incidence of osteosarcomas and stomach tumors, and tumor latency. The spectrum of tumors observed for this Brca2 germline mouse model suggest that it faithfully recapitulates some human disease phenotypes associated with BRCA2 loss. In addition, these findings include extensive in vivo data demonstrating that germline Brca2 and p53 mutations cooperatively affect animal survivals, tumor susceptibilities, and tumor onsets. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, Res Triangle Pk, NC 27711 USA. Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. NCI, Lab Biosyst & Canc, Genome Struct & Funct Sect, Bethesda, MD 20892 USA. Constella Hlth Sci, Durham, NC 27708 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Primate Res Ctr, Madison, WI 53706 USA. AstraZeneca R&D, Boston, MA 02451 USA. RP McAllister, KA (reprint author), NIEHS, NIH, MD EC-21,79 Alexander Dr,Bldg 4401, Res Triangle Pk, NC 27709 USA. EM mcallis2@nihs.nih.gov NR 57 TC 7 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 2 BP 187 EP 198 DI 10.1080/01926230600611794 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 042FG UT WOS:000237512700007 PM 16546942 ER PT J AU Erexson, CR Faucette, LJ AF Erexson, CR Faucette, LJ TI Immunohistochemistry and in situ hybridization SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. RP Erexson, CR (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike,Bldg 31,Rm 7A03, Bethesda, MD 20892 USA. EM cerexson@niaid.nih.gov; lfaucette@niaid.nih.gov NR 0 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 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 2 BP 206 EP 207 DI 10.1080/01926230600654075 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 042FG UT WOS:000237512700009 ER PT J AU Dunnick, J Blackshear, P Kissling, G Cunningham, M Parker, J Nyska, A AF Dunnick, J. Blackshear, P. Kissling, G. Cunningham, M. Parker, J. Nyska, A. TI Critical pathways in heart function: Bis(2-chloroethoxy)methane-induced heart gene transcript change in F344 rats SO TOXICOLOGIC PATHOLOGY LA English DT Article DE bis(2-chloroethoxy)methane; cardiotoxicity; mitochondria damage; gene changes; F344 rat ID ENDOTHELIAL GROWTH-FACTOR; CELL-CELL ADHESION; CARDIAC STEM-CELLS; UNCOUPLING PROTEINS; IN-VIVO; MITOCHONDRIAL DYSFUNCTION; MYOCARDIAL REGENERATION; INTRACELLULAR CALCIUM; REGULATES EXPRESSION; THIODIGLYCOLIC ACID AB Gene transcript changes after exposure to the heart toxin, bis(2-chloroethoxy)methane (CEM), were analyzed to elucidate mechanisms in cardiotoxicity and recovery. CEM was administered to 5-week-old male F344/N rats at 0, 200, 400, or 600 mg/kg by dermal exposure, 5 days per week, for a total of 12 doses by study day 16. Heart toxicity occurred after 2 days of dosing in all 3 regions of the heart (atrium, ventricle, interventricular septum) and was characterized by myofiber vacuolation, necrosis, mononuclear-cell infiltration, and atrial thrombosis. Ultrastructural analysis revealed that the primary site of damage was the mitochondrion. By day 5, even though dosing was continued, the toxic lesions in the heart began to resolve, and by study day 16, the heart appeared histologically normal. RNA was extracted from whole hearts after 2 or 5 days of CEM dosing. After a screen for transcript change by microarray analysis, dose-response trends for selected transcripts were analyzed by qRT-PCR. The selected transcripts code for proteins involved in energy production, control of calcium levels, and maintenance of heart function. The down-regulation of ATP subunit transcripts (Atp5j, ATP5k), which reside in the mitochondrial membranes, indicated a decrease in energy supply at day 2 and day 5. This was accompanied by down-regulation of transcripts involved in high-energy consumption processes such as membrane transport and ion channel transcripts (e.g., abc1a, kcnj12). The up-regulation of transcripts encoding for temperature regulation and calcium binding proteins (ucp1 and calb3) only at the 2 low exposure levels, suggest that these adaptive processes cannot occur in association with severe cardiotoxicity as seen in hearts at the high exposure level. Transcript expression changes occurred within 2 days of CEM exposure, and were dose-and time-dependent. The heart transcript changes suggest that CEM cardiotoxicity activates protective processes associated energy conservation and maintenance of heart function. C1 NIEHS, ETP, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Constella Grp, Res Triangle Pk, NC 27709 USA. RP Dunnick, J (reprint author), NIEHS, ETP, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunnickj@niehs.nih.gov FU NIEHS NIH HHS [ES-35513] NR 80 TC 11 Z9 12 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 4 BP 348 EP 356 DI 10.1080/01926230600798583 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 064KY UT WOS:000239089600004 PM 16844662 ER PT J AU Elmore, S Lanning, L Allison, N Vallant, M Nyska, A AF Elmore, S. Lanning, L. Allison, N. Vallant, M. Nyska, A. TI The transduction of rat submandibular glands by an adenoviral vector carrying the human growth hormone gene is associated with limited and reversible changes at the infusion site SO TOXICOLOGIC PATHOLOGY LA English DT Article DE adenovirus; hydroxychloroquine; submandibular salivary gland; gene therapy ID SALIVARY-GLANDS; ENDOCRINE SECRETION; EXOCRINE GLANDS; IN-VIVO; ERYTHROPOIETIN; THERAPEUTICS; ENLARGEMENT; AMPUTATION; PROTEINS; DELIVERY AB Adenoviral vectors have been shown to efficiently deliver exogenous genes to salivary glands and have therefore been investigated as tools for the treatment of human disease. The purpose of this study was to evaluate the response of F344 rats to intraductal infusion of the right submandibular salivary gland with an adenoviral vector encoding the gene for human growth hormone (AdCMVhGH). Co-administration of hydroxychloroquine (HCQ) was used to redirect the secretion of human growth hormone (hGH) from saliva into serum. This paper documents the findings of the pathology evaluation of this National Toxicology Program study. The right submandibular salivary gland (infusion site) was the primary target organ, with microscopic lesions characteristic of a mild to moderate insult observed at 3 days post infusion in vector exposed animals. These lesions were characterized by variable degrees of acute glandular inflammation, degeneration and necrosis, with more severe lesions in the higher dose groups. Rats at 28 days post infusion had milder inflammation, degeneration and necrosis compared to day 3 rats, with variable degrees of regeneration. In conclusion, the effects on the salivary glands are reversible as indicated by the milder inflammation and degeneration in the day 28 rats concomitant with mild to moderate regeneration. Therefore, the vector appears relatively innocuous with limited tissue toxicity. C1 Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Otsuka Maryland Res Inst, Rockville, MD 20850 USA. Expt Pathol Lab, Res Triangle Pk, NC 27709 USA. RP Elmore, S (reprint author), Natl Inst Environm Hlth Sci, Environm Toxicol Program, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU NIDCR NIH HHS [Z01 DE000336-23]; NIEHS NIH HHS [E01-ES-95446] NR 37 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 4 BP 385 EP 392 DI 10.1080/01926230600815189 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 064KY UT WOS:000239089600008 PM 16844666 ER PT J AU Maronpot, RR AF Maronpot, R. R. TI A monograph on histomorphologic evaluation of lymphoid organs SO TOXICOLOGIC PATHOLOGY LA English DT Article ID IMMUNOTOXICITY; MICE; GUIDELINES; IMMUNE C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Maronpot, RR (reprint author), NIEHS, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM maronpot@niehs.nih.gov NR 12 TC 4 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 407 EP 408 DI 10.1080/01926230600978466 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700001 PM 17067936 ER PT J AU Elmore, SA AF Elmore, Susan A. TI Histopathology of the lymph nodes SO TOXICOLOGIC PATHOLOGY LA English DT Article DE lymph node; immunotoxic; xenobiotic; hyperplasia; angiectasis; lymphoma ID HISTIOCYTIC SARCOMA; MICE; GUIDELINE; NEOPLASMS; ADJUVANT; RAT AB Lymph nodes function as filters of tissues and tissue fluids and are sites of origin and production of lymphocytes for normal physiological functions. As part of this normal function, they react to both endogenous and exogenous substances with a variety of specific morphological and functional responses. Lesions can be both proliferative and nonproliferative, and can be treatment-related or not. The histological evaluation of lymph nodes is necessary in order to understand the immunotoxic effects of chemicals with the resulting data providing an important component of human risk assessment. It is the challenge of the toxicologic pathologist to interpret the pathology data within the complete clinical evaluation of the entire animal. Daily insults, ageing and toxins can alter the normal histology and primary function of lymph nodes. Therefore it is important to distinguish and differentiate lesions that occur naturally during normal development and ageing from those that are induced by xenobiotics. To achieve this goal, comparison with strain- age- and sex-matched controls is crucial. C1 Natl Inst Environm Hlth Sci, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), Natl Inst Environm Hlth Sci, Lab Expt Pathol, NIH, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU Intramural NIH HHS [001-1520-808, Z99 ES999999] NR 19 TC 22 Z9 24 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 425 EP 454 DI 10.1080/01926230600964722 PG 30 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700003 PM 17067938 ER PT J AU Travlos, GS AF Travlos, Gregory S. TI Normal structure, function, and histology of the bone marrow SO TOXICOLOGIC PATHOLOGY LA English DT Article DE lymphopoiesis; hematopoiesis; fixation; decalcification; M : E ratio ID BIOPSY SPECIMENS; CELLS; MOUSE; SPLEEN; RATS; MODEL AB While a complete blood count provides information regarding possible treatment-related effects reflected in the peripheral blood, morphological evaluation of bone marrow cytology and paraffin sections provides information about bone marrow tissue architecture that otherwise would be missed by examination of peripheral blood alone. In decalcified, paraffin-embedded, hematoxylin and eosin (H&E)-stained sections of bone marrow, the more mature stages of the erythroid and myeloid cells, adipocytes, mast cells, and megakaryocytes can be identified, but lymphoid cells as well as immature progenitor cells can not be reliably identified. The quality of the marrow sections is governed by numerous variables related to specimen collection and processing and must be considered. In addition to discussing normal structure, function, and histology of bone marrow, methods for preparation and evaluation of bone marrow are presented. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Travlos, GS (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM travlos@niehs.nih.gov FU Intramural NIH HHS NR 55 TC 84 Z9 86 U1 3 U2 19 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 548 EP 565 DI 10.1080/01926230600939856 PG 18 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700008 PM 17067943 ER PT J AU Travlos, GS AF Travlos, Gregory S. TI Histopathology of bone marrow SO TOXICOLOGIC PATHOLOGY LA English DT Article DE M : E ratio; myelodysplasia; stromal cells; fibrous osteodystrophy; metastasis ID INFLAMMATORY DISEASE; F344 RATS; ANEMIA; MICE; DOG; THROMBOCYTOPENIA; EMPERIPOLESIS; LEUKOCYTE AB As a major hematopoietic and lymphoid organ, morphological evaluation of the bone marrow is an important component of toxicity or safety assessment studies. While definitive characterization of bone marrow lesions often requires cytological aspirates or smears, assessment of histological bone marrow sections provides information regarding tissue architecture and hematopoietic status that is relevant for the detection of direct or indirect responses to chemical exposure. A variety of lesions have been observed in bone marrow. For example, lesions involving disturbances in growth, degenerative changes, inflammatory changes and neoplasia have been described. Lesions identified in hematoxylin and eosin-stained sections typically represent changes in the hematopoietic cell lineage and/or stromal cells since definitive identification of lymphoid cells is difficult except in cases of lymphoma. This review provides a descriptive and pictorial representation of a wide range of bone marrow lesions. Since large animal-to-animal variation may exist and there can be collection site- and age- related differences, it is imperative that the pathologist reviews all potential treatment-related findings against appropriate concurrent controls. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Travlos, GS (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM travlos@niehs.nih.gov FU Intramural NIH HHS NR 53 TC 32 Z9 32 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 566 EP 598 DI 10.1080/01926230600964706 PG 33 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700009 PM 17067944 ER PT J AU Ward, JM Erexson, CR Faucette, LJ Foley, JF Dijkstra, C Cattoretti, G AF Ward, Jerrold M. Erexson, Cindy R. Faucette, Lawrence J. Foley, Julie F. Dijkstra, Christine Cattoretti, Giorgio TI Immunohistochemical markers for the rodent immune system SO TOXICOLOGIC PATHOLOGY LA English DT Article DE tissue fixation; antigen retrieval; rat; mouse; B cells; T cells ID PARAFFIN-EMBEDDED RAT; MONOCLONAL-ANTIBODIES; MOUSE-TISSUES; T-CELL; MICE; ANTIGENS AB The responses to insults including chemical toxins, irradiation and infectious agents involve morphologic, biochemical and molecular changes in the immune system. The changes in specific tissues and cells often can be detected by histopathology and its associated field of immunohistochemisty (IHC). Cells normally express specific proteins (antigens) that can be detected by IHC. When responses to xenobiotics occur, cells often up or down regulate proteins. The art of IHC requires specialized procedures for detection of antigens. Fixation, tissue processing, immunoreactions and antigen retrieval methods are important elements of IHC. We review the antibodies, their sources, use of frozen or fixed parafin-embedded tissues and specific IHC methods including antigen retrieval and illustrate how they can be effectively used to characterize the immunotoxicologic effects of agents. C1 NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. VU Univ, Med Ctr, Dept Mol Cell Biol & Immunol, NL-1081 HV Amsterdam, Netherlands. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. RP Ward, JM (reprint author), NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. EM jw116y@nih.gov OI Cattoretti, Giorgio/0000-0003-3799-3221 NR 11 TC 23 Z9 23 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 616 EP 630 DI 10.1080/0192623060094134 PG 15 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700012 PM 17067947 ER PT J AU Maronpot, RR AF Maronpot, R. R. TI Enhanced histopathology of lymphoid tissues SO TOXICOLOGIC PATHOLOGY LA English DT Article ID IMMUNE-SYSTEM; PATHOLOGY CONSIDERATIONS; RISK ASSESSMENT; IMMUNOTOXICITY; GUIDELINES; CHEMICALS; TOXICOLOGY C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Maronpot, RR (reprint author), NIEHS, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM maronpot@niehs.nih.gov NR 24 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 631 EP 633 DI 10.1080/01926230600978474 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700013 PM 17067948 ER PT J AU Elmore, SA AF Elmore, Susan A. TI Enhanced histopathology of the lymph nodes SO TOXICOLOGIC PATHOLOGY LA English DT Article DE lymph node; follicle; cortex; paracortex; medulla ID RAT AB Routine histopathology of lymphoid organs is the cornerstone in the identification of immunotoxic and immunomodulatory compounds. Enhanced histopathology is a systematic approach that can be used to further characterize, both qualitatively and semi-quantitatively, the immunomodulatory effects that may occur within both primary and secondary lymphoid organs. The lymph nodes are the major route of entry for antigens and pathogens, via the afferent lymph flow, and they can be sensitive indicators of compounds with regional or systemic immunomodulatory/toxic effects and should therefore be included in the battery of lymphoid organs to evaluate for enhanced histopathology. As with all lymphoid organs, the separate compartments should be evaluated independently and descriptive rather than interpretive terminology should be used to characterize changes within those compartments. This data, in conjunction with gross findings, clinical pathology and changes in organ weight (i.e., thymus), will enable the pathologist to determine if a significant effect on the immune system is present. Moreover, this data may enable the pathologist to determine the critical site or compartment in the targeted tissue, provide some indication of target cell population (B or T cell) and characterize a dose-response relationship. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 5 TC 11 Z9 13 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 634 EP 647 DI 10.1080/01926230600939997 PG 14 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700014 PM 17067949 ER PT J AU Elmore, SA AF Elmore, Susan A. TI Enhanced histopathology of the spleen SO TOXICOLOGIC PATHOLOGY LA English DT Article DE spleen; red pulp; white pulp; PALS; marginal zone; follicles ID IMMUNE-SYSTEM; IMMUNOTOXICITY; PATHOLOGY AB The spleen is the largest secondary lymphoid organ, is considered the draining site for compounds that are administered intravenously, and is therefore considered an important organ to evaluate for treatment-related lesions. Due to the presence of B and T lymphocytes, the immunotoxic effects of xenobiotics or their metabolites on these cell populations may be reflected in the spleen. Therefore it is one of the recommended organs to evaluate for enhanced histopathology of the immune system. The two major functional zones of the spleen are the hematogenous red pulp and the lymphoid white pulp (periarteriolar sheaths, follicles and marginal zones). For enhanced histopathology, these splenic compartments should be evaluated separately for changes in size and cellularity, and descriptive rather than interpretive terminology should be used to characterize any changes (Haley et al., 2005). Moreover, germinal center development within the lymphoid follicles should be noted as increased or decreased. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), NIEHS, Lab Expt Pathol, NIH, MD B3-06, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 9 TC 29 Z9 33 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 648 EP 655 DI 10.1080/01926230600865523 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700015 PM 17067950 ER PT J AU Elmore, SA AF Elmore, Susan A. TI Enhanced histopathology of the thymus SO TOXICOLOGIC PATHOLOGY LA English DT Article DE apoptosis; cortex; medulla; tingible body macrophage; stress response ID APOPTOSIS; CELLS; IMMUNOTOXICITY; CHEMICALS; ORGANS; RATS AB The thymus is a primary or central lymphoid organ in which T lymphocytes undergo diffentiation and maturation autonomously within the cortex, without the need for antigenic stimulation, and it is essential for the normal development and function of the immune system. The thymus has been shown to be a sensitive target organ following exposure to immunotoxicants and endogenous corticosteroids, and a decrease in size or weight is often one of the first noted measures of compound-induced effects with cortical lymphocytes (thymocytes) being especially susceptible. Therefore, changes in thymus histopathology and architecture are considered to be of particular relevance for immunotoxicity screening. The separate compartments in each lymphoid organ should be evaluated separately and descriptive rather than interpretive terminology should be used to characterize changes within those compartments (Haley et al., 2005). Therefore, enhanced histopathological evaluation of the thymus involves the determination of the size and cellularity of the cortex and medulla, which should be noted separately. Other changes to evaluate include, but are not limited to, increased lymphocyte apoptosis, lymphocyte necrosis, cortex: medulla ratio and an increase or decrease in the epithelial component of the thymus. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 21 TC 39 Z9 41 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 656 EP 665 DI 10.1080/01926230600865556 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700016 PM 17067951 ER PT J AU Elmore, SA AF Elmore, Susan A. TI Enhanced histopathology of the bone marrow SO TOXICOLOGIC PATHOLOGY LA English DT Article DE bone marrow; erythroid; myeloid; megakaryocytes; myeloid : erythroid ratio; maturation index AB Changes in bone marrow cellularity can be an indicator of systemic toxicity and, therefore, bone marrow should be included in the battery of tissues examined for enhanced histopathology. However, the majority of changes in the bone marrow that are observed in toxicology studies are a response to hematological changes or lesions elsewhere in the body. For this reason, a consideration of all tissue changes in the body is required in order to differentiate toxic effects versus physiological responses in the bone marrow. While enhanced histopathology involves evaluation of the separate compartments in each lymphoid organ using descriptive rather than interpretive terminology, bone marrow is unique in that it lacks specific compartments. Furthermore, identification of erythroid, myeloid, megakaryocytic, and stromal cells, plus adipose tissue and hemosiderin-laden macrophages, can be accomplished from conventional H&E-stained sections, but conclusive identification of lymphoid lineage cells is not likely. This limits the extent of initial enhanced histopathology on bone marrow and argues for the use of cytological preparations for more comprehensive assessment of potential immunomodulatory effects. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 Alexander Dr,MD B3-06, Res Triangle Pk, NC 27709 USA. EM elmore@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 7 TC 18 Z9 18 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 666 EP 686 DI 10.1080/01926230600939971 PG 21 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700017 PM 17067952 ER PT J AU Elmore, SA AF Elmore, Susan A. TI Enhanced histopathology of mucosa-associated lymphoid tissue SO TOXICOLOGIC PATHOLOGY LA English DT Article DE MALT; NALT; GALT; BALT; follicles; germinal centers; interfollicular area ID IMMUNE-SYSTEM; CELLS AB The secretory epithelial surfaces of the body are a major route of entry for potentially pathogenic substances. The organized mucosal lymphoid tissues that are found within the gastrointestinal and respiratory tracts are therefore particularly important as a first line of defense against harmful compounds. The major function of these mucosa-associated lymphoid tissues (MALT) is to initiate local IgA immune responses, which are then passed on to draining lymph nodes. For enhanced histopathology, the separate compartments of each lymphoid tissue should be evaluated separately for changes in size and lymphocyte cellularity and descriptive rather than interpretive terminology should be used to characterize any changes. The organization of MALT is similar to that of lymph nodes with B-cell-rich follicles and T-cell-rich interfollicular areas. Therefore, these two compartments should be evaluated separately for changes in size and lymphocyte cellularity and the germinal center development within lymphoid follicles should be evaluated as well. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Elmore, SA (reprint author), NIEHS, Lab Expt Pathol, NIH, 111 Alexander Dr,Md B3-06, Res Triangle Pk, NC 27709 USA. EM Elmore@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 9 TC 17 Z9 18 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 5 BP 687 EP 696 DI 10.1080/01926230600939989 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 098KZ UT WOS:000241520700018 PM 17067953 ER PT J AU Cardiff, RD Anver, MR Boivin, GP Bosenberg, MW Maronpot, RR Molinolo, AA Nikitin, AY Rehg, JE Thomas, GV Russell, RG Ward, JM AF Cardiff, Robert D. Anver, Miriam R. Boivin, Gregory P. Bosenberg, Marcus W. Maronpot, Robert R. Molinolo, Alfredo A. Nikitin, Alexander Yu Rehg, Jerold E. Thomas, George V. Russell, Robert G. Ward, Jerrold M. TI Precancer in mice: Animal models used to understand, prevent, and treat human precancers SO TOXICOLOGIC PATHOLOGY LA English DT Article DE precancer; mouse; models; GEM (Genetic Engineered Mice); pathology; preclinical; trials ID ABERRANT CRYPT FOCI; GENETICALLY-ENGINEERED MICE; CARCINOMA IN-SITU; PROSTATIC INTRAEPITHELIAL NEOPLASIA; HUMAN BREAST-CANCER; MIN MOUSE MODEL; TRANSGENIC MICE; CONSENSUS REPORT; CYCLOOXYGENASE-2 INHIBITOR; ADENOMATOUS POLYPOSIS AB We present a status report from the NCI Mouse Models of Human Cancers Consortium (MMHCC) Precancers Workshop held November 8 and 9, 2004. An expert panel, the Mouse Models Group (MMG) evaluated the status of mouse models of precancer emphasizing genetically engineered mouse models, especially of lining epithelium and their utilitarian value to human carcinogenesis. An outline of the background for the panel's considerations is provided with examples of past and current precancerous lesions in mice. The experimental use of oncogenic viruses and chemical carcinogens in mice led to operational definitions of initiation, promotion, and preneoplasia Preneoplastic and precancerous lesions are found in these models. In this precancer concept, most preneoplastic lesions are considered as potentially precancerous or at least an earlier stage in cancer development than typical pre-invasive epithelial lesions, which are often seen in these mouse models. Genetically engineered mice, used to test the oncogenicity of individual genes, develop precancers that are initiated by defined molecular and histopathologic changes. The mouse can be used to isolate and study precancers in detail, thereby providing a level of biological understanding not readily available in clinical disease. These studies suggest that genetically engineered mice are very useful preclinical models for chemoprevention and therapy. C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. SAIC Frederick Inc, NCI, Pathol Histotechnol Lab, Frederick, MD 21702 USA. Vet Affairs Med Ctr, Cincinnati, OH 45220 USA. Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45220 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90095 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. SoBran Inc, Bethesda, MD 20892 USA. RP Cardiff, RD (reprint author), Univ Calif Davis, Ctr Comparat Med, Hutchison Dr & CR 98, Davis, CA 95616 USA. EM rdcardif@ucdavis.edu FU NCI NIH HHS [P30 CA093373-01, CA84291-07, N01- CO-12400, K08 CA89124, P01CA071907, R01 CA089140, R01 CA96823, U01 CA084294, U01 CA105490-01, R01 CA98778-01, R01 CA112054]; NCRR NIH HHS [K26 RR017595, U42 RR14905]; NIBIB NIH HHS [R01 EB00561] NR 70 TC 24 Z9 24 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 699 EP 707 DI 10.1080/01926230600930129 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800001 PM 17074738 ER PT J AU Ward, JM Wobus, CE Thackray, LB Erexson, CR Faucette, LJ Belliot, G Barron, EL Sosnovtsev, SV Green, KY AF Ward, Jerrold M. Wobus, Christiane E. Thackray, Larissa B. Erexson, Cindy R. Faucette, Larry J. Belliot, Gael Barron, Elyssa L. Sosnovtsev, Stanislav V. Green, Kim Y. TI Pathology of immunodeficient mice with naturally occurring murine norovirus infection SO TOXICOLOGIC PATHOLOGY LA English DT Article DE hepatitis; murine norovirus; immunodeficient mice; dendritic cells; caliciviruses; pneumonia ID LATENT GAMMAHERPESVIRUS INFECTION; T-CELL RESPONSE; FELINE CALICIVIRUS; INNATE IMMUNITY; PERSISTENCE; DISEASE; VIRUS; SITES; STAT1 AB Murine norovirus (MNV) was recently discovered in Rag2(-/-)/Stat1(-/-) mice in a U.S. medical research facility. Presently, little is known concerning the epidemiology and natural history of this virus. We studied the pathology of naturally occurring MNV infection in 28 immunodeficient mice of several different genotypes (Rag1(-/-)IFN gamma R-/-, OT1 Rag1(-/-) IFN gamma R-/-, OT2 Rag1(-/-)IFN gamma R-/-, Rag1(-/-)/Stat1(-/-), and Rag2(-/-)) that were maintained in two U.S. research facilities. The mice were selected for study because sentinel mice housed in their holding rooms had been identified as positive for MNV-specific antibodies during routine screening for infectious agents. Our data indicate that in certain lines of immunodeficient mice, MNV can establish a disseminated infection that is characteristically associated with inflammation in multiple tissues, including liver (hepatitis), lung (focal interstitial pneumonia) and the peritoneal and pleural cavities. In addition, MNV can establish an asymptomatic infection in the mesenteric lymph nodes of Rag2(-/-) mice. Further studies are needed to determine whether MNV presents a confounding variable in immunological, toxicological and pathological studies in mice naturally infected with MNV. C1 NIAID, Infect Dis Pathogenesis Sect, Comarat Med Branch, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Ward, JM (reprint author), NIAID, Infect Dis Pathogenesis Sect, Comarat Med Branch, NIH, Twinbrook 3,Room 2W-01A,MSC 8135, Bethesda, MD 20892 USA. EM jeward@mail.nih.gov FU NIAID NIH HHS [AI007163, R01 AI054483]; PHS HHS [U54 A1057160] NR 23 TC 68 Z9 71 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 708 EP 715 DI 10.1080/01926230600918876 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800002 PM 17074739 ER PT J AU Houle, CD Ton, TVT Clayton, N Huff, J Hong, HHL Sills, RC AF Houle, Christopher D. Ton, Thai-Vu T. Clayton, Natasha Huff, James Hong, Hue-Hua L. Sills, Robert C. TI Frequent p53 and H-ras mutations in benzene- and ethylene oxide-induced mammary gland carcinomas from B6C3F1 mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE p53; H-ras; benzene; ethylene oxide; mammary gland carcinoma; mice; carcinogen ID TUMOR-SUPPRESSOR GENE; OXIDATIVE DNA-DAMAGE; IN-VIVO MUTAGENICITY; CELL-CYCLE ARREST; ONCOGENIC RAS; BONE-MARROW; K-RAS; INHALATION EXPOSURE; LUNG-TUMORS; INDUCED HEMATOTOXICITY AB Benzene and ethylene oxide are multisite carcinogens in rodents and classified as human carcinogens by the National Toxicology Program. In 2-year mouse studies, both chemicals induced mammary carcinomas. We examined spontaneous, benzene-, and ethylene oxide-induced mouse mammary carcinomas for p53 protein expression, using immunohistochemistry, and p53 (exons 5-8) and H-ras(codon 61) mutations using cycle sequencing techniques. p53 protein expression was detected in 42% (8/19) of spontaneous, 43% (6/14) of benzene-, and 67% (8/12) of ethylene oxide-induced carcinomas. However, semiquantitative evaluation of p53 protein expression revealed that benzene- and ethylene oxide-induced carcinomas exhibited expression levels five- to six-fold higher than spontaneous carcinomas. p53 mutations were found in 58% (7/12) of spontaneous, 57% (8/14) of benzene-, and 67% (8/12) of ethylene oxide-induced carcinomas. H-ras mutations were identified in 26% (5/19) of spontaneous, 50% (7/14) of benzene-, and 33% (4/12) of ethylene oxide-induced carcinomas. When H-ras mutations were present, concurrent p53mutations were identified in 40% (2/5) of spontaneous, 71% (5/7) of benzene-, and 75% (3/4) of ethylene oxide-induced carcinomas. Our results demonstrate that p53 and H-ras mutations are relatively common in control and chemically induced mouse mammary carcinomas although both chemicals can alter the mutational spectra and more commonly induce concurrent mutations. C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. NIH, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. N Carolina State Univ, Expt Pathol Labs Inc, Raleigh, NC 27606 USA. RP Houle, CD (reprint author), Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. EM houle@niehs.nih.gov FU Intramural NIH HHS NR 80 TC 6 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 752 EP 762 DI 10.1080/01926230600935912 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800008 PM 17162533 ER PT J AU Foley, JF Collins, JB Umbach, DM Grissom, S Boorman, GA Heinloth, AN AF Foley, Julie F. Collins, Jennifer B. Umbach, David M. Grissom, Sherry Boorman, Gary A. Heinloth, Alexandra N. TI Optimal sampling of rat liver tissue for toxicogenomic studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver; acetaminophen; histology; pathology; microarray; rat; necrosis ID GENE-EXPRESSION CHANGES; TOXICITY; DIET AB Different degrees of a toxic response between and within the various lobes of the liver have been observed in rodents following treatment with acetaminophen. This study was designed to compare 2 sampling methods of the rat liver for gene-expression analysis. Ten male Fischer 344/N rats, 12-14 weeks of age, were treated with vehicle (0.5% aqueous ethyl cellulose) or acetaminophen (APAP, 1500 mg/kg) and sacrificed 24 hours following dose administration. Two representative sections were collected from the left liver lobe, stained with hematoxylin and eosin (H&E), and evaluated independently by 2 pathologists. The central core of the left lobe was cubed and frozen. Five random cubes were conserved, while the remaining left lobe core was pulverized. From each of the 10 animals, 2 random cubes and 2 samples from the homogeneous, pulverized samples were prepared for microarray analysis. Histopathologic evaluation revealed a variable response of centrilobular necrosis within the left lobe. Multiple methods used to analyze the microarray data indicated that sampling technique was not a major contributor to the variability observed in the gene expression data; however, only the powdered samples clustered for all animals, even those with disparate histopathologic results. Additionally, a powdered sample provided the advantages of a homogenous sample pool and the ability to use sample aliquots for other analyses to include proteomics, metabonomics, and other molecular techniques. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Foley, JF (reprint author), NIEHS, Lab Expt Pathol, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM foley1@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 15 TC 12 Z9 12 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 795 EP 801 DI 10.1080/01926230601009527 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800012 PM 17162537 ER PT J AU King-Herbert, A Thayer, K AF King-Herbert, Angela Thayer, Kristina TI NTP workshop: Animal models for the NTP rodent cancer bioassay: Stocks and strains - Should we switch? SO TOXICOLOGIC PATHOLOGY LA English DT Article DE animal models; National Toxicology Program; F344; B6C3F1; cancer bioassay ID CARCINOGENICITY AB The National Toxicology Program (NTP) hosted a workshop, "Animal Models for the NTP Rodent Cancer Bioassay: Strains and Stocks-Should We Switch?" on June 16-17, 2005, at the National Institute of Environmental Health Sciences (NIEHS) in Research Triangle Park, North Carolina. The workshop's objectives were to determine (1) whether the currently used models, the F344/N rat and B6C3F1/N mouse, continue to be appropriate to identify substances that may pose a carcinogenic hazard for humans and (2) whether the NTP should consider conducting cancer bioassays using multiple strains of rats and/or mice to better capture the range of genetic variability. Workshop participants advised the NTP to discontinue using the current F344/N strain due to the recent issues with fertility, seizure activity, and chylothorax and provided several options on how the program should approach identifying and selecting a new rat model. Participants believed that the B6C3F1/N mouse is still appropriate for use by the NTP, but suggested the NTP take steps to better understand and address increases in background rates of liver tumors in this strain. Finally, the participants supported the NTP exploring the use of the multiple strain approach, although they raised many questions concerning data interpretation and feasibility. This article also outlines the NTP's next steps in pursuing the workshop recommendations. C1 NIEHS, NTP, Res Triangle Pk, NC 27709 USA. RP King-Herbert, A (reprint author), NIEHS, NTP, POB 12233,3 Alexander Dr,B3-06, Res Triangle Pk, NC 27709 USA. EM kingher1@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 10 TC 42 Z9 42 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 802 EP 805 DI 10.1080/01926230600935938 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800013 PM 17162538 ER PT J AU Fonger, GC Goshorn, JC Snyder, JW AF Fonger, George Charles Goshorn, Jeanne C. Snyder, Jack W. TI Toxicological information resources at the National Library of Medicine SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 NIH, Natl Lib Med, Div Specialized Informat Serv, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20892 USA. RP Snyder, JW (reprint author), NIH, Natl Lib Med, Div Specialized Informat Serv, Toxicol & Environm Hlth Informat Program, Bethesda, MD 20892 USA. EM snyderj@mail.nlm.nih.gov NR 0 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 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 6 BP 812 EP 813 DI 10.1080/01926230601034657 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 108CL UT WOS:000242217800015 PM 17162542 ER PT J AU Lobenhofer, EK Boorman, GA Phillips, KL Heinloth, AN Malarkey, DE Blackshear, PE Houle, C Hurban, P AF Lobenhofer, Edward K. Boorman, Gary A. Phillips, Kenneth L. Heinloth, Alexandra N. Malarkey, David E. Blackshear, Pamela E. Houle, Christopher Hurban, Patrick TI Application of visualization tools to the analysis of histopathological data enhances biological insight and interpretation SO TOXICOLOGIC PATHOLOGY LA English DT Article DE information visualization; phenotypic anchor; histopathology; gene expression; acute hepatocyte toxicity ID INVASIVE BREAST-CARCINOMA; BASAL-LIKE SUBTYPE; EXPRESSION PATTERNS; MICROARRAY; TOXICITY; GOMINER; LIVER AB Gene expression profiling, metabolomic screens, and other high-dimensional methods have become an integral part of many biological investigations. To facilitate interpretation of these data, it is important to have detailed phenotypic data - including histopathology - to which these data can be associated, or anchored. However, as the amount of phenotypic data increases, associations within and across these data can be difficult to visualize and interpret. We have developed an approach for categorizing and clustering biologically related histopathological diagnoses to facilitate their visualization, thereby increasing the possibility of identifying associations and facilitating the comparison with other data streams. In this study, we utilize histopathological data generated as part of a standardized toxicogenomics compendium study to generate composite histopathological scores and to develop visualizations that facilitate biological insight. The validity of this approach is illustrated by the identification of transcripts that correlate with the pathology diagnoses that comprise the categories of "response to hepatocellular injury" and "repair." This approach is broadly applicable to studies in which histopathology is used to phenotypically anchor other data, and results in visualizations that facilitate biological interpretation and the identification of associations and relationships within the data. C1 Cogenics, Morrisville, NC 27560 USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. RP Lobenhofer, EK (reprint author), Cogenics, 100 Perimeter Pk,Suite C, Morrisville, NC 27560 USA. EM elobenhofer@cogenics.com FU Intramural NIH HHS; NIEHS NIH HHS [ES-33513, N01-ES-25497] NR 19 TC 18 Z9 21 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 921 EP 928 DI 10.1080/01926230601072319 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200008 PM 17178692 ER PT J AU Yanaihara, N Hussain, SP Yokota, J Croce, C Harris, CC AF Yanaihara, Nozomu Hussain, S. Perwez Yokota, Jun Croce, Carlo Harris, Curtis C. TI Microenvironment and cancer: Inflammation and MicroRNA SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract ID NITRIC-OXIDE C1 NCI, Human Carcinogenesis Lab, CCR, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan. Ohio State Univ, Inst Genet, Columbus, OH 43210 USA. NR 4 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 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2006 VL 34 IS 7 BP 972 EP 972 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 118VI UT WOS:000242971200016 ER EF