FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Fu, YP Kohaar, I Mumy, A Tang, W Muchmore, B Porter-Gill, P Liu, LY Figueroa, J Garcia-Closas, M Baris, D Purdue, M Thun, M Albanes, D Malats, N Real, FX Kogevinas, M Johnson, A Schwenn, M Chanock, S Rothman, N Silverman, D Prokunina-Olsson, L AF Fu, Yi-Ping Kohaar, Indu Mumy, Adam Tang, Wei Muchmore, Brian Porter-Gill, Patricia Liu, Luyang Figueroa, Jonine Garcia-Closas, Montserrat Baris, Dalsu Purdue, Mark Thun, Michael Albanes, Demetrius Malats, Nuria Real, Francisco X. Kogevinas, Manolis Johnson, Alison Schwenn, Molly Chanock, Stephen Rothman, Nathaniel Silverman, Debra Prokunina-Olsson, Ludmila TI A novel functional variant in 8q24 is associated with regulation of prostate stem cell antigen (PSCA) gene expression and bladder cancer risk SO GENOME BIOLOGY LA English DT Meeting Abstract ID SUSCEPTIBILITY C1 [Fu, Yi-Ping; Kohaar, Indu; Mumy, Adam; Tang, Wei; Muchmore, Brian; Porter-Gill, Patricia; Liu, Luyang; Chanock, Stephen; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Thun, Michael] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA. [Malats, Nuria; Real, Francisco X.] Spanish Natl Canc Res Ctr, Madrid 28029, Spain. [Kogevinas, Manolis] Ctr Res Environm Epidemiol, Barcelona 08003, Spain. [Schwenn, Molly] Maine Canc Registry, Augusta, ME 04333 USA. [Johnson, Alison] Vermont Canc Registry, Burlington, VT 05401 USA. RI Albanes, Demetrius/B-9749-2015; Malats, Nuria/H-7041-2015; Kogevinas, Manolis/C-3918-2017 OI Malats, Nuria/0000-0003-2538-3784; NR 2 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P4 BP 5 EP 6 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700019 ER PT J AU Kohaar, I Scott-Johnson, A Fu, YP Porter-Gill, P Prokunina-Olsson, L AF Kohaar, Indu Scott-Johnson, Alexandra Fu, Yi-Ping Porter-Gill, Patricia Prokunina-Olsson, Ludmila TI Functional exploration of CCNE1 splicing forms as a possible link to bladder cancer susceptibility SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Kohaar, Indu; Scott-Johnson, Alexandra; Fu, Yi-Ping; Porter-Gill, Patricia; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P7 BP 8 EP 8 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700022 ER PT J AU Mumy, A Kohaar, I Porter-Gill, P Tang, W Fu, YP Prokunina-Olsson, L AF Mumy, Adam Kohaar, Indu Porter-Gill, Patricia Tang, Wei Fu, Yi-Ping Prokunina-Olsson, Ludmila TI Prostate stem cell antigen (PSCA) and risk of bladder cancer: linking genotypes to functional mechanisms SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Mumy, Adam; Kohaar, Indu; Porter-Gill, Patricia; Tang, Wei; Fu, Yi-Ping; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, 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 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P15 BP 11 EP 12 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700028 ER PT J AU Porter-Gill, P Fu, YP Kaushiva, A Price, D Dahut, W Figg, W Prokunina-Olsson, L AF Porter-Gill, Patricia Fu, Yi-Ping Kaushiva, Alpana Price, Douglas Dahut, William Figg, William Prokunina-Olsson, Ludmila TI Detection of bladder, breast and prostate cancer using serum and tissue miRNA profiling SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Porter-Gill, Patricia; Fu, Yi-Ping; Kaushiva, Alpana; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Price, Douglas; Dahut, William; Figg, William] NCI, Mol Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P18 BP 12 EP 13 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700031 ER PT J AU Puigbo, P Mekhedov, S Wolf, YI Koonin, EV AF Puigbo, Pere Mekhedov, Sergei Wolf, Yuri I. Koonin, Eugene V. TI A comprehensive census of horizontal gene transfers from prokaryotes to unikonts SO GENOME BIOLOGY LA English DT Meeting Abstract ID TREE; LIFE C1 [Puigbo, Pere; Mekhedov, Sergei; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. NR 5 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 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P20 BP 13 EP 14 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700033 ER PT J AU Tang, W Prokunina-Olsson, L AF Tang, Wei Prokunina-Olsson, Ludmila TI Whole transcriptome sequencing of normal and tumor bladder tissue samples SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Tang, Wei; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P23 BP 14 EP 15 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700036 ER PT J AU Tarway, M Tang, W Prokunina-Olsson, L AF Tarway, McAnthony Tang, Wei Prokunina-Olsson, Ludmila TI Identification of functional genetic variants associated with prostate cancer through analysis of genome-wide genetic and epigenetic datasets SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Tarway, McAnthony; Tang, Wei; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, 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 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P24 BP 15 EP 15 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700037 ER PT J AU Yutin, N Makarova, KS Wolf, YI Koonin, EV AF Yutin, Natalya Makarova, Kira S. Wolf, Yuri I. Koonin, Eugene V. TI Phylogenomics of prokaryotic ribosomal proteins SO GENOME BIOLOGY LA English DT Meeting Abstract C1 [Yutin, Natalya; Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 SU 1 MA P30 BP 18 EP 18 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QH UT WOS:000308546700043 ER PT J AU Biesecker, LG Shianna, KV Mullikin, JC AF Biesecker, Leslie G. Shianna, Kevin V. Mullikin, Jim C. TI Exome sequencing: the expert view SO GENOME BIOLOGY LA English DT Editorial Material AB To complement our special issue on exome sequencing, Genome Biology asked several leaders in the field for their views on this new approach. Leslie G Biesecker (LGB), Jim C Mullikin (JM) and Kevin V Shianna (KVS) discuss the reasons for the popularity of exome sequencing and its contribution to genomics. C1 [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Biesecker, Leslie G.; Mullikin, Jim C.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Shianna, Kevin V.] Duke Univ, Sch Med, Genome Anal Facil, Duke Ctr Human Genome Variat, Durham, NC 27710 USA. [Mullikin, Jim C.] NHGRI, Comparat Genom Unit, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov NR 0 TC 27 Z9 28 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 9 SI SI AR 128 DI 10.1186/gb-2011-12-9-128 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 874AH UT WOS:000298926900016 PM 21920051 ER PT J AU Dittmer, T Misteli, T AF Dittmer, Travis Misteli, Tom TI The lamin protein family SO GENOME BIOLOGY LA English DT Review ID A-TYPE LAMINS; INTERMEDIATE-FILAMENT PROTEINS; DREIFUSS MUSCULAR-DYSTROPHY; GILFORD-PROGERIA-SYNDROME; SQUAMOUS-CELL CARCINOMA; NEIGHBOR-JOINING METHOD; NUCLEAR-PORE COMPLEXES; B-TYPE LAMINS; DNA-REPLICATION; MAMMALIAN-CELLS AB The lamins are the major architectural proteins of the animal cell nucleus. Lamins line the inside of the nuclear membrane, where they provide a platform for the binding of proteins and chromatin and confer mechanical stability. They have been implicated in a wide range of nuclear functions, including higher-order genome organization, chromatin regulation, transcription, DNA replication and DNA repair. The lamins are members of the intermediate filament (IF) family of proteins, which constitute a major component of the cytoskeleton. Lamins are the only nuclear IFs and are the ancestral founders of the IF protein superfamily. Lamins polymerize into fibers forming a complex protein meshwork in vivo and, like all IF proteins, have a tripartite structure with two globular head and tail domains flanking a central a-helical rod domain, which supports the formation of higher-order polymers. Mutations in lamins cause a large number of diverse human diseases, collectively known as the laminopathies, underscoring their functional importance. C1 [Dittmer, Travis; Misteli, Tom] NCI, NIH, Bethesda, MD 20896 USA. RP Dittmer, T (reprint author), NCI, NIH, Bethesda, MD 20896 USA. EM dittmert@mail.nih.gov NR 129 TC 107 Z9 110 U1 1 U2 14 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 5 AR 222 DI 10.1186/gb-2011-12-5-222 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 831LR UT WOS:000295732700004 PM 21639948 ER PT J AU Jiang, HY Li, N Gopalan, V Zilversmit, MM Varma, S Nagarajan, V Li, J Mu, JB Hayton, K Henschen, B Yi, M Stephens, R McVean, G Awadalla, P Wellems, TE Su, XZ AF Jiang, Hongying Li, Na Gopalan, Vivek Zilversmit, Martine M. Varma, Sudhir Nagarajan, Vijayaraj Li, Jian Mu, Jianbing Hayton, Karen Henschen, Bruce Yi, Ming Stephens, Robert McVean, Gilean Awadalla, Philip Wellems, Thomas E. Su, Xin-zhuan TI High recombination rates and hotspots in a Plasmodium falciparum genetic cross SO GENOME BIOLOGY LA English DT Article ID SIZE-DEPENDENT CONTROL; LOW-COMPLEXITY REGIONS; MEIOTIC RECOMBINATION; HOT-SPOTS; MALARIA PARASITE; HUMAN GENOME; SACCHAROMYCES-CEREVISIAE; SELECTIVE SWEEPS; MAP; SEQUENCE AB Background: The human malaria parasite Plasmodium falciparum survives pressures from the host immune system and antimalarial drugs by modifying its genome. Genetic recombination and nucleotide substitution are the two major mechanisms that the parasite employs to generate genome diversity. A better understanding of these mechanisms may provide important information for studying parasite evolution, immune evasion and drug resistance. Results: Here, we used a high-density tiling array to estimate the genetic recombination rate among 32 progeny of a P. falciparum genetic cross (7G8 x GB4). We detected 638 recombination events and constructed a high-resolution genetic map. Comparing genetic and physical maps, we obtained an overall recombination rate of 9.6 kb per centimorgan and identified 54 candidate recombination hotspots. Similar to centromeres in other organisms, the sequences of P. falciparum centromeres are found in chromosome regions largely devoid of recombination activity. Motifs enriched in hotspots were also identified, including a 12-bp G/C-rich motif with 3-bp periodicity that may interact with a protein containing 11 predicted zinc finger arrays. Conclusions: These results show that the P. falciparum genome has a high recombination rate, although it also follows the overall rule of meiosis in eukaryotes with an average of approximately one crossover per chromosome per meiosis. GC-rich repetitive motifs identified in the hotspot sequences may play a role in the high recombination rate observed. The lack of recombination activity in centromeric regions is consistent with the observations of reduced recombination near the centromeres of other organisms. C1 [Jiang, Hongying; Li, Jian; Mu, Jianbing; Hayton, Karen; Henschen, Bruce; Wellems, Thomas E.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Li, Na] Medimmune Inc, Gaithersburg, MD 20878 USA. [Gopalan, Vivek; Varma, Sudhir; Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. [Zilversmit, Martine M.] Univ Montreal, Charles Bruneau Cancerol Ctr, Fac Med, Ste Justine Res Ctr, Montreal, PQ H3T 1C5, Canada. [Li, Jian] Xiamen Univ, State Key Lab Stress Cell Biol, Sch Life Sci, Xiamen 361005, Fujian, Peoples R China. [Yi, Ming; Stephens, Robert] NCI, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [McVean, Gilean] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Awadalla, Philip] Univ Montreal, Dept Pediat, Fac Med, Ste Justine Res Ctr, Montreal, PQ H3T 1C5, Canada. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM xsu@niaid.nih.gov RI Varma, Sudhir/N-8763-2014; OI Varma, Sudhir/0000-0002-4096-4782; Su, Xinzhuan/0000-0003-3246-3248 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank Jun Yang and Brandie Fullmer at the Laboratory of Immunopathogenesis and Bioinformatics, SAIC Frederick, Inc. for microarray hybridizations, Dr Anton Persikov for advice and discussion on zinc finger proteins and their binding characteristics, and NIAID intramural editor Brenda Rae Marshall for assistance. NR 50 TC 41 Z9 42 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 4 AR R33 DI 10.1186/gb-2011-12-4-r33 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 794BW UT WOS:000292871100001 PM 21463505 ER PT J AU Peng, WQ Zhao, KJ AF Peng, Weiqun Zhao, Keji TI An integrated strategy for identification of both sharp and broad peaks from next-generation sequencing data SO GENOME BIOLOGY LA English DT Editorial Material DE ChIP-Seq; algorithms; SICER; ZINBA; Chromatin States; Epigenetics; epigenome ID CHIP-SEQ DATA; HUMAN GENOME; DOMAINS AB A novel integrative approach has been developed by Lieb and colleagues for analyzing genome-wide datasets of different chromatin-binding factors and epigenetic states that exhibit both sharp and diffuse signals on the genome. C1 [Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA. [Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Peng, WQ (reprint author), George Washington Univ, Dept Phys, 725 21st St NW, Washington, DC 20052 USA. EM wpeng@gwu.edu; zhaok@nhlbi.nih.gov FU National Heart, Lung and Blood Institute, NIH FX We thank Brian Abraham for critical reading of the manuscript. This work was supported by the Division of Intramural Research Program of National Heart, Lung and Blood Institute, NIH (KZ). NR 10 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 7 AR 120 DI 10.1186/gb-2011-12-7-120 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 843BX UT WOS:000296648400010 PM 21787381 ER PT J AU Shriner, D Adeyemo, A Ramos, E Chen, GJ Rotimi, CN AF Shriner, Daniel Adeyemo, Adebowale Ramos, Edward Chen, Guanjie Rotimi, Charles N. TI Mapping of disease-associated variants in admixed populations SO GENOME BIOLOGY LA English DT Review ID GENOME-WIDE ASSOCIATION; LONG-RANGE INTERACTION; DENSITY ADMIXTURE MAP; AFRICAN-AMERICANS; PROSTATE-CANCER; COLORECTAL-CANCER; GENETIC-VARIATION; SNP ARRAYS; RISK LOCUS; C-MYC AB A more refined estimation of ancestry would benefit admixture mapping and association mapping, making disease loci identification in admixed populations more powerful. C1 [Shriner, Daniel; Adeyemo, Adebowale; Ramos, Edward; Chen, Guanjie; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. RP Shriner, D (reprint author), NHGRI, Ctr Res Genom & Global Hlth, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA. EM shrinerda@mail.nih.gov; rotimic@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health [S06GM008016-320107, S06GM008016-380111, 2M01RR010284]; Center for Research on Genomics and Global Health; National Human Genome Research Institute; National Institute of Diabetes and Digestive and Kidney Diseases; Center for Information Technology; Office of the Director at the National Institutes of Health [1ZIAHG200362-02] FX The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. The Howard University Family Study was supported by National Institutes of Health grants S06GM008016-320107 and S06GM008016-380111. Enrollment was carried out at the Howard University General Clinical Research Center, supported by National Institutes of Health grant 2M01RR010284. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health. The Center for Research on Genomics and Global Health is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (1ZIAHG200362-02). Genotyping support was provided by the Coriell Institute for Medical Research. The funding bodies had no role in the design of the study, or collection and analysis of data, or in the decision to publish. NR 61 TC 24 Z9 25 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 5 AR 223 DI 10.1186/gb-2011-12-5-223 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 831LR UT WOS:000295732700005 PM 21635713 ER PT J AU Zhu, M Yi, M Kim, CH Deng, CX Li, Y Medina, D Stephens, RM Green, JE AF Zhu, Min Yi, Ming Kim, Chang Hee Deng, Chuxia Li, Yi Medina, Daniel Stephens, Robert M. Green, Jeffrey E. TI Integrated miRNA and mRNA expression profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage SO GENOME BIOLOGY LA English DT Article ID HUMAN BREAST-CANCER; MICRORNA EXPRESSION; GENE-EXPRESSION; TRANSGENIC MICE; PROGENITOR CELLS; MESENCHYMAL TRANSITION; ESTROGEN-RECEPTOR; POOR-PROGNOSIS; PROTEIN BMI-1; FUSION GENE AB Background: MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs involved in regulating gene expression and protein translation. miRNA expression profiling of human breast cancers has identified miRNAs related to the clinical diversity of the disease and potentially provides novel diagnostic and prognostic tools for breast cancer therapy. In order to further understand the associations between oncogenic drivers and miRNA expression in sub-types of breast cancer, we performed miRNA expression profiling on mammary tumors from eight well-characterized genetically engineered mouse (GEM) models of human breast cancer, including MMTV-H-Ras, -Her2/neu, -c-Myc, -PymT, -Wnt1 and C3(1)/SV40 T/t-antigen transgenic mice, BRCA1(fl/fl); p53(+/-); MMTV-cre knockout mice and the p53(fl/fl); MMTV-cre transplant model. Results: miRNA expression patterns classified mouse mammary tumors according to luminal or basal tumor subtypes. Many miRNAs found in luminal tumors are expressed during normal mammary development. miR-135b, miR-505 and miR-155 are expressed in both basal human and mouse mammary tumors and many basal-associated miRNAs have not been previously characterized. miRNAs associated with the initiating oncogenic event driving tumorigenesis were also identified. miR-10b, -148a, -150, -199a and -486 were only expressed in normal mammary epithelium and not tumors, suggesting that they may have tumor suppressor activities. Integrated miRNA and mRNA gene expression analyses greatly improved the identification of miRNA targets from potential targets identified in silico. Conclusions: This is the first large-scale miRNA gene expression study across a variety of relevant GEM models of human breast cancer demonstrating that miRNA expression is highly associated with mammary tumor lineage, differentiation and oncogenic pathways. C1 [Zhu, Min; Green, Jeffrey E.] NCI, Transgen Oncogenesis & Genom Sect, Lab Cell Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, FCRDC, Frederick, MD 21702 USA. [Kim, Chang Hee] NCI, Lab Mol Technol, FCRDC, Frederick, MD 21702 USA. [Deng, Chuxia] NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD 20892 USA. [Li, Yi] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Medina, Daniel] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Green, JE (reprint author), NCI, Transgen Oncogenesis & Genom Sect, Lab Cell Biol & Genet, Ctr Canc Res, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA. EM jegreen@nih.gov RI deng, chuxia/N-6713-2016 FU National Institutes of Health, Center for Cancer Research, NCI FX We thank Dr Kent Hunter for generously providing MMTV-PymT mouse mammary tumor samples, Dr Peter Blumberg for critically reading the manuscript, and Mary Albaugh for technical assistance with animal handling. This work was supported in part by the National Institutes of Health intramural program, Center for Cancer Research, NCI. NR 56 TC 30 Z9 31 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2011 VL 12 IS 8 AR R77 DI 10.1186/gb-2011-12-8-r77 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 843CI UT WOS:000296649500007 PM 21846369 ER PT J AU Jjingo, D Huda, A Gundapuneni, M Marino-Ramirez, L Jordan, IK AF Jjingo, Daudi Huda, Ahsan Gundapuneni, Madhumati Marino-Ramirez, Leonardo Jordan, I. King TI Effect of the Transposable Element Environment of Human Genes on Gene Length and Expression SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE gene expression; gene regulation; selection hypothesis; genomic design hypothesis; L1; MIR ID HUMAN HOUSEKEEPING GENES; HUMAN GENOME; INTERSPERSED REPEATS; MAMMALIAN GENOMES; SHORT INTRONS; GC CONTENT; SELECTION; TRANSCRIPTOMES; SEQUENCE; DATABASE AB Independent lines of investigation have documented effects of both transposable elements (TEs) and gene length (GL) on gene expression. However, TE gene fractions are highly correlated with GL, suggesting that they cannot be considered independently. We evaluated the TE environment of human genes and GL jointly in an attempt to tease apart their relative effects. TE gene fractions and GL were compared with the overall level of gene expression and the breadth of expression across tissues. GL is strongly correlated with overall expression level but weakly correlated with the breadth of expression, confirming the selection hypothesis that attributes the compactness of highly expressed genes to selection for economy of transcription. However, TE gene fractions overall, and for the L1 family in particular, show stronger anticorrelations with expression level than GL, indicating that GL may not be the most important target of selection for transcriptional economy. These results suggest a specific mechanism, removal of TEs, by which highly expressed genes are selectively tuned for efficiency. MIR elements are the only family of TEs with gene fractions that show a positive correlation with tissue-specific expression, suggesting that they may provide regulatory sequences that help to control human gene expression. Consistent with this notion, MIR fractions are relatively enriched close to transcription start sites and associated with coexpression in specific sets of related tissues. Our results confirm the overall relevance of the TE environment to gene expression and point to distinct mechanisms by which different TE families may contribute to gene regulation. C1 [Jjingo, Daudi; Huda, Ahsan; Gundapuneni, Madhumati; Jordan, I. King] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Gundapuneni, Madhumati] Inst Syst Biol, Seattle, WA USA. [Marino-Ramirez, Leonardo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Marino-Ramirez, Leonardo; Jordan, I. King] PanAmer Bioinformat Inst, Santa Marta, Magdalena, Colombia. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. EM king.jordan@biology.gatech.edu RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Fulbright predoctoral fellowship; School of Biology, Georgia Institute of Technology; Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology [BR-4839]; National Institute of Health, National Library of Medicine, NCBI FX We would like to thank Nathan J. Bowen for guidance on the gene expression analysis. We would like to thank members of the Jordan lab for their support and technical assistance. D.J. was supported by a Fulbright predoctoral fellowship. I.K.J. and A.H. were supported by the School of Biology, Georgia Institute of Technology, and an Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology (BR-4839). This research was supported in part by the Intramural Research Program of the National Institute of Health, National Library of Medicine, NCBI. NR 40 TC 10 Z9 11 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2011 VL 3 BP 259 EP 271 DI 10.1093/gbe/evr015 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 759NG UT WOS:000290252700024 PM 21362639 ER PT J AU Auffray, C Caulfield, T Khoury, MJ Lupski, JR Schwab, M Veenstra, T AF Auffray, Charles Caulfield, Timothy Khoury, Muin J. Lupski, James R. Schwab, Matthias Veenstra, Timothy TI Genome Medicine: past, present and future SO GENOME MEDICINE LA English DT Editorial Material C1 [Auffray, Charles] CNRS Inst Biol Sci, F-94801 Villejuif, France. [Caulfield, Timothy] Univ Alberta, Fac Law, Edmonton, AB T6G 2T4, Canada. [Caulfield, Timothy] Univ Alberta, Sch Publ Hlth, Edmonton, AB T6G 2T4, Canada. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. [Schwab, Matthias] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70367 Stuttgart, Germany. [Schwab, Matthias] Univ Hosp, Dept Clin Pharmacol, Inst Expt & Clin Pharmacol & Toxicol, D-72076 Tubingen, Germany. [Veenstra, Timothy] NCI, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. RP Auffray, C (reprint author), CNRS Inst Biol Sci, F-94801 Villejuif, France. FU NCRR NIH HHS [M01 RR000188]; NINDS NIH HHS [R01 NS058529] NR 32 TC 10 Z9 11 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 6 DI 10.1186/gm220 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400006 PM 21345269 ER PT J AU de Wit, E Feldmann, H Munster, VJ AF de Wit, Emmie Feldmann, Heinz Munster, Vincent J. TI Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies SO GENOME MEDICINE LA English DT Review AB Since its discovery in 1976, Ebolavirus has caused periodic outbreaks of viral hemorrhagic fever associated with severe and often fatal disease. Ebolavirus is endemic in Central Africa and the Philippines. Although there is currently no approved treatment available, the past 10 years has seen remarkable progress in our understanding of the pathogenicity of Ebolavirus and the development of prophylactic and post-exposure therapies against it. In vitro and in vivo experiments have shown that Ebolavirus pathogenicity is multifactorial, including viral and host determinants. Besides their function in the virus replication cycle, the viral glycoprotein, nucleoprotein, minor matrix protein and polymerase cofactor are viral determinants of pathogenicity, with evasion of the host innate and adaptive immune responses as the main mechanism. Although no licensed Ebolavirus vaccines are currently available, vaccine research in non-human primates, the 'gold standard' animal model for Ebolavirus, has produced several promising candidates. A combination of DNA vaccination and a recombinant adenovirus serotype 5 boost resulted in cross-protective immunity in non-human primates. A recombinant vesicular stomatitis vaccine vector protected non-human primates in pre- and post-exposure challenge studies. Several antiviral therapies are currently under investigation, but only a few of these have been tested in non-human primate models. Antisense therapies, in which oligonucleotides inhibit viral replication, have shown promising results in non-human primates following post-exposure treatment. In light of the severity of Ebolavirus disease and the observed increase in Ebolavirus outbreaks over the past decade, the expedited translation of potential candidate therapeutics and vaccines from bench to bedside is currently the most challenging task for the field. Here, we review the current state of Ebolavirus research, with emphasis on prophylactic and therapeutic intervention strategies. C1 [de Wit, Emmie; Feldmann, Heinz; Munster, Vincent J.] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA. RP Munster, VJ (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM vincent.munster@niaid.nih.gov OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The authors thank Anita Mora for help with figure design. This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 95 TC 7 Z9 10 U1 0 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 5 DI 10.1186/gm219 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400005 PM 21349211 ER PT J AU Huang, Y Ballinger, DG Dai, JY Peters, U Hinds, DA Cox, DR Beilharz, E Chlebowski, RT Rossouw, JE McTiernan, A Rohan, T Prentice, RL AF Huang, Ying Ballinger, Dennis G. Dai, James Y. Peters, Ulrike Hinds, David A. Cox, David R. Beilharz, Erica Chlebowski, Rowan T. Rossouw, Jacques E. McTiernan, Anne Rohan, Thomas Prentice, Ross L. TI Genetic variants in the MRPS30 region and postmenopausal breast cancer risk SO GENOME MEDICINE LA English DT Article AB Background: Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest. Methods: We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r(2)) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction. Results: The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343. Conclusions: Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk. C1 [Huang, Ying; Dai, James Y.; Peters, Ulrike; McTiernan, Anne; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Huang, Ying; Dai, James Y.; Peters, Ulrike; McTiernan, Anne; Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Vaccine & Infect Dis, Seattle, WA 98109 USA. [Ballinger, Dennis G.; Cox, David R.; Beilharz, Erica] Perlegen Sci Inc, Mountain View, CA 94043 USA. [Hinds, David A.] 23andMe Inc, Mountain View, CA 94043 USA. [Chlebowski, Rowan T.] Harbor UCLA Res & Educ Inst, Div Med Oncol Hematol, Torrance, CA 90502 USA. [Rossouw, Jacques E.] NHLBI, NIH, Prevent & Populat Sci Program, Bethesda, MD 20892 USA. [Rohan, Thomas] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM rprentic@fhcrc.org FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268200764314C, N01WH22110, 24152, 32100 2, 32105 6, 32108 9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, 44221]; National Cancer Institute [CA53996, CA148065]; AstraZeneca; Novartis; Pfizer; Eli Lilly; Amgen FX Decisions concerning study design, data collection and analysis, interpretation of the results, the preparation of the manuscript, or the decision to submit the manuscript for publication resided with committees composed of WHI investigators that included NHLBI representatives. Program Office: (National Heart, Lung, and Blood Institute, Bethesda, MD, USA) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L Kooperberg; (Medical Research Labs, Highland Heights, KY, USA) Evan Stein; (University of California at San Francisco, San Francisco, CA, USA) Steven Cummings. Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY, USA) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX, USA) Haleh Sangi-Haghpeykar; (Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA) JoAnn E Manson; (Brown University, Providence, RI, USA) Charles B Eaton; (Emory University, Atlanta, GA, USA) Lawrence S Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) Shirley Beresford; (George Washington University Medical Center, Washington, DC, USA) Lisa Martin; (Los Angeles Biomedical Research Institute at Harbor- UCLA Medical Center, Torrance, CA, USA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR, USA) Erin LeBlanc; (Kaiser Permanente Division of Research, Oakland, CA, USA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI, USA) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC, USA) Barbara V Howard; (Northwestern University, Chicago/Evanston, IL, USA) Linda Van Horn; (Rush Medical Center, Chicago, IL, USA) Henry Black; (Stanford Prevention Research Center, Stanford, CA, USA).; Marcia L Stefanick; (State University of New York at Stony Brook, Stony Brook, NY, USA) Dorothy Lane; (The Ohio State University, Columbus, OH, USA) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL, USA) Cora E Lewis; (University of Arizona, Tucson/Phoenix, AZ, USA) Cynthia A Thomson; (University at Buffalo, Buffalo, NY, USA) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA, USA) John Robbins; (University of California at Irvine, CA, USA) F Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA, USA) Lauren Nathan; (University of California at San Diego, LaJolla/Chula Vista, CA, USA) Robert D Langer; (University of Cincinnati, Cincinnati, OH, USA) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL, USA) Marian Limacher; (University of Hawaii, Honolulu, HI, USA) J David Curb; (University of Iowa, Iowa City/Davenport, IA, USA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA, USA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ, USA) Norman Lasser; (University of Miami, Miami, FL, USA) Mary Jo O'Sullivan; (University of Minnesota, Minneapolis, MN, USA) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC, USA) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA, USA) Lewis Kuller; (University of Tennessee Health Science Center, Memphis, TN, USA) Karen C Johnson; (University of Texas Health Science Center, San Antonio, TX, USA) Robert Brzyski; (University of Wisconsin, Madison, WI, USA) Gloria E Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Mara Vitolins; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI, USA) Michael S Simon. Women's Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Sally Shumaker. This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [contracts HHSN268200764314C, N01WH22110, 24152, 32100 2, 32105 6, 32108 9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, and 44221]. Clinical Trials Registration: ClinicalTrials.gov identifier, NCT00000611. The work of Dr Prentice was partially supported by grants CA53996 and CA148065 from the National Cancer Institute.; RTC reports receiving consulting fees from AstraZeneca, Novartis, Pfizer, and Eli Lilly, lecture fees from AstraZeneca and Novartis, and grant support from Amgen. No other potential conflict of interest relevant to this article was reported. NR 31 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 42 DI 10.1186/gm258 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400042 PM 21702935 ER PT J AU Kratz, CP Bratslavsky, G Shi, JX AF Kratz, Christian P. Bratslavsky, Gennady Shi, Jianxin TI The clinical utility of testicular cancer risk loci SO GENOME MEDICINE LA English DT Article AB Three recent genome-wide association studies of testicular germ cell tumors have uncovered predisposition alleles in or near several genes, including KITLG, BAK1, SPRY4, TERT, ATF7IP, and DMRT1. The calculated per-allele odds ratio for variants in the region of KITLG is the highest reported for any malignancy so far. These findings are in agreement with epidemiological data indicating that testicular cancer has a higher heritability than most other cancers. Here, we discuss the question of whether the newly identified risk polymorphisms can be used to guide patient care. C1 [Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Shi, Jianxin] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Kratz, CP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA. EM kratzcp@mail.nih.gov; Jianxin.Shi@nih.gov FU Intramural Research Program of the National Institutes of Health; National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Cancer Institute. We are grateful to Mark H Greene for insightful comments. NR 10 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-994X J9 GENOME MED JI Genome Med. PY 2011 VL 3 AR 1 DI 10.1186/gm215 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA V27QJ UT WOS:000208627400001 PM 21255381 ER PT J AU Alkan, C Cardone, MF Catacchio, CR Antonacci, F O'Brien, SJ Ryder, OA Purgato, S Zoli, M Della Valle, G Eichler, EE Ventura, M AF Alkan, Can Cardone, Maria Francesca Catacchio, Claudia Rita Antonacci, Francesca O'Brien, Stephen J. Ryder, Oliver A. Purgato, Stefania Zoli, Monica Della Valle, Giuliano Eichler, Evan E. Ventura, Mario TI Genome-wide characterization of centromeric satellites from multiple mammalian genomes SO GENOME RESEARCH LA English DT Article ID CENP-B; DNA-SEQUENCES; X-CHROMOSOME; MONODELPHIS-DOMESTICA; REGIONS; EVOLUTION; PHYLOGENY; PRIMATES; PROTEIN; ORGANIZATION AB Despite its importance in cell biology and evolution, the centromere has remained the final frontier in genome assembly and annotation due to its complex repeat structure. However, isolation and characterization of the centromeric repeats from newly sequenced species are necessary for a complete understanding of genome evolution and function. In recent years, various genomes have been sequenced, but the characterization of the corresponding centromeric DNA has lagged behind. Here, we present a computational method (RepeatNet) to systematically identify higher-order repeat structures from unassembled whole-genome shotgun sequence and test whether these sequence elements correspond to functional centromeric sequences. We analyzed genome datasets from six species of mammals representing the diversity of the mammalian lineage, namely, horse, dog, elephant, armadillo, opossum, and platypus. We define candidate monomer satellite repeats and demonstrate centromeric localization for five of the six genomes. Our analysis revealed the greatest diversity of centromeric sequences in horse and dog in contrast to elephant and armadillo, which showed high-centromeric sequence homogeneity. We could not isolate centromeric sequences within the platypus genome, suggesting that centromeres in platypus are not enriched in satellite DNA. Our method can be applied to the characterization of thousands of other vertebrate genomes anticipated for sequencing in the near future, providing an important tool for annotation of centromeres. C1 [Alkan, Can; Antonacci, Francesca; Eichler, Evan E.; Ventura, Mario] Univ Washington, Howard Hughes Med Inst, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Cardone, Maria Francesca; Catacchio, Claudia Rita; Ventura, Mario] Univ Bari, Dept Genet & Microbiol, I-70126 Bari, Italy. [O'Brien, Stephen J.] NCI Frederick, Lab Genom Divers, Frederick, MD 21702 USA. [Ryder, Oliver A.] Zool Soc San Diego, San Diego, CA 92112 USA. [Purgato, Stefania; Zoli, Monica; Della Valle, Giuliano] Univ Bologna, Dipartimento Biol Evoluzionist Sperimentale, I-40126 Bologna, Italy. RP Ventura, M (reprint author), Univ Washington, Howard Hughes Med Inst, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. EM mventura@uw.edu RI Alkan, Can/D-2982-2009; Ventura, Mario/E-6420-2011; Cardone, Maria Francesca/G-8818-2012; Antonacci, Francesca/F-5457-2013; Catacchio, Claudia/P-8898-2015 OI Alkan, Can/0000-0002-5443-0706; Ventura, Mario/0000-0001-7762-8777; Cardone, Maria Francesca/0000-0002-7597-7313; Antonacci, Francesca/0000-0002-5833-6186; Catacchio, Claudia/0000-0002-2166-723X FU PRIN 2007; [HG002385] FX We thank G. Aksay for her help in implementing RepeatNet and T. Brown for proofreading the manuscript. This work is partly supported by a HG002385 grant to E.E.E. and a PRIN 2007 grant to M.V. E.E.E. is an investigator of the Howard Hughes Medical Institute. NR 59 TC 31 Z9 31 U1 0 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2011 VL 21 IS 1 BP 137 EP 145 DI 10.1101/gr.111278.110 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 702BC UT WOS:000285868300014 PM 21081712 ER PT S AU Dosemeci, A AF Dosemeci, Ayse BE Clelland, JD TI Proteomic Analysis of the Postsynaptic Density SO GENOMICS, PROTEOMICS, AND THE NERVOUS SYSTEM SE Advances in Neurobiology LA English DT Article; Book Chapter DE Postsynaptic density; PSD; Mass spectrometry; Proteomics; Electron microscopy ID PROTEIN-KINASE-II; TANDEM MASS-SPECTROMETRY; LONG-TERM POTENTIATION; GLUTAMATE-RECEPTOR SUBUNITS; EXCITATORY SYNAPSES; RAT-BRAIN; ULTRASTRUCTURAL-LOCALIZATION; ABSOLUTE QUANTIFICATION; MULTIPROTEIN COMPLEXES; HIPPOCAMPAL SLICES AB The postsynaptic density (PSD) is a large protein complex lining the postsynaptic membrane with an average mass around 1 million KDa. The structure appears to be an organized array containing neurotransmitter receptors and signal transduction molecules held together by specialized scaffold proteins. PSDs can be isolated by subcellular fractionation, the most widely used protocols consisting of detergent treatment of synaptosomal fractions followed by further density gradient centrifugation steps. Several groups used mass spectrometric approaches to identify proteins in these PSD fractions. An inherent problem in the determination of PSD composition through analysis of isolated fractions has been the presence of contaminants. A method for further purification of PSD fractions by an orthogonal affinity-based strategy and comparison of the parent and purified preparations to trace the enrichment of proteins allows the compilation of a more restricted list of putative PSD components. Ultimately, however, the presence of the identified proteins at the PSD has to be confirmed by immuno-electron microscopy. Proteomic techniques for relative quantification of proteins are applied for the detection of those proteins whose abundance in the PSD change following synaptic activity, as well as in response to various pathological conditions such as ischemia. C1 Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Dosemeci, A (reprint author), Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM dosemeca@mail.nih.gov NR 63 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2190-5215 BN 978-1-4419-7196-8 J9 ADV NEUROBIOL JI Adv. Neurobiol. PY 2011 VL 2 BP 227 EP 249 DI 10.1007/978-1-4419-7197-5_9 D2 10.1007/978-1-4419-7197-5 PG 23 WC Biology; Genetics & Heredity; Neurosciences SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity; Neurosciences & Neurology GA BSW89 UT WOS:000285983800009 ER PT J AU Bingel, U Colloca, L Vase, L AF Bingel, Ulrike Colloca, Luana Vase, Lene TI Mechanisms and Clinical Implications of the Placebo Effect: Is There a Potential for the Elderly? A Mini-Review SO GERONTOLOGY LA English DT Review DE Placebo; Nocebo; Neurobiology; Placebo effect, clinical implications; Aging ID IRRITABLE-BOWEL-SYNDROME; SYNDROME IBS PATIENTS; PARKINSONS-DISEASE; ANALGESIC RESPONSE; EXPECTATION; PAIN; TRIALS; ANXIETY; NETWORK; POLYMORPHISMS AB In recent years, the placebo effect has been a topic of considerable interest both in the scientific and the clinical community. In this time, the placebo effect has evolved from being considered a nuisance in clinical and pharmacological research to becoming a neurobiological phenomenon worthy of scientific investigation in its own right. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. These psychosocially induced biochemical changes in a patient's brain and body may in turn affect the course of a disease and the response to a therapy. Here we summarize and discuss the current insights into placebo mechanisms and discuss the potentially widespread implications for research and clinical practice. Even though a systematic knowledge of placebo effects across the lifespan is lacking, we aim at highlighting specific aspects related to the care of elderly patients and those suffering from neurodegenerative diseases. Copyright (C) 2010 S. Karger AG, Basel C1 [Bingel, Ulrike] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, DE-20246 Hamburg, Germany. [Vase, Lene] Aarhus Univ, Dept Psychol, Aarhus, Denmark. [Colloca, Luana] NCCAM, Dept Bioeth, Ctr Clin, NIH, Bethesda, MD USA. RP Bingel, U (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Martinistr 52, DE-20246 Hamburg, Germany. EM bingel@uke.uni-hamburg.de OI Colloca, Luana/0000-0002-6503-4709 FU BMBF; Regione Piemonte; International Association for Study of Pain; ViFAB FX This work was supported by the BMBF (U.B.), Regione Piemonte and International Association for Study of Pain (L.C.) and ViFAB (L.V.). NR 61 TC 10 Z9 11 U1 2 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PY 2011 VL 57 IS 4 BP 354 EP 363 DI 10.1159/000322090 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 782XC UT WOS:000292045100008 PM 20975261 ER PT B AU Nash, TE AF Nash, Theodore E. BE Lujan, HD Svard, S TI Antigenic Variation in Giardia SO GIARDIA: A MODEL ORGANISM LA English DT Article; Book Chapter ID VARIANT SURFACE PROTEIN; CYSTEINE-RICH PROTEIN; EXCRETORY-SECRETORY PRODUCTS; LAMBLIA CLONE GS/M-83-H7; IMMUNE-RESPONSE; GENE FAMILY; IMMUNOGLOBULIN-A; ZINC-BINDING; IN-VITRO; INFECTIONS AB Giardia lamblia trophozoites undergo surface antigenic variation where one member of a family of related proteins, variant specific surface proteins (VSPs), is expressed but periodically replaced by another. It is the only intestinal dwelling organism to do this. Switching occurs spontaneously in culture in vitro in the absence of defined environmental triggers. The two major Giardia groups infecting humans differ in rates of VSP switching, which vary from once every 6.5 to 12-13 generations, nature of the vsp repertoires and occurrence of switching during encystation/excystation. VSPs are cysteine-rich with many CXXC motifs whose positions are indicative of the VSP subgroup. The cysteines are non-reactive most likely because of disulfide bond formation, which creates conformational epitopes. The most characteristic feature of VSPs is an absolutely conserved carboxyl terminal CRGKA tail, which is post-translationally modified by palmitoylation of the cysteine and modification of the arginine to citrulline. The function of these modifications is unclear but both affect antibody-mediated cytotoxicity. A well-conserved membrane-spanning region is immediately proximal to the tail. VSPs vary dramatically in size and a subset has tandem repeating amino acid units near the amino terminus that can differ in size, number, sequence, and antigenicity. Some are known to be immunodominant. Unique surface Zn finger and GGCY motifs of unclear function are present in a majority. VSPs are secreted into the medium by an undefined proteolytic process that cleaves the VSP close to the membrane-spanning region; the fate of the residual palmitate-containing fragment has not been studied. With the exception of closely related VSPs, they are antigenically distinct and possess individual features that impart differentiating physical chemical characteristics. Similar to the role of surface proteins of other organisms that undergo antigenic variation, VSPs are essential for the development of immunity, immune selection, and immune evasion as well as biological selection. The latter operates in humans and experimental animals in the absence of an adaptive immune system or before adaptive immune responses develop. Only certain VSPs are compatible in the intestine of specific host and organisms that express these survive and grow. Additionally, populated VSPs are also unrecognized by the host's immune system. These constraints likely limit the number of VSPs that can be expressed in an infected individual. VSPs are most diverse at the amino terminus, the portion of the VSPs that interfaces most directly with the intestine and the immune responses of the host. Antibodies directed to the amino terminus are cytotoxic in vitro and lead to immune selection and replacement with VSPs unrecognized by the host in vivo. Experimental animals immunized to all VSPs are resistant to challenge infection. The WB isolate has a repertoire of about 270 vsp genes, only one of which is present on the surface of an organism. How switching occurs is unclear. Unlike the process in African trypanosomes, the process is epigenetic since there is no gene movement and vsps are not overly represented at the telomeres. There is good evidence that RNAi-based post-transcriptional mechanisms are involved in the control of VSP expression but how switching occurs and only one VSP is expressed remain unclear. C1 [Nash, Theodore E.] NIAID, Clin Parasitol Unit, NIH, Bethesda, MD 20892 USA. [Nash, Theodore E.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nash, TE (reprint author), NIAID, Clin Parasitol Unit, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 72 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA BN 978-3-7091-0197-1 PY 2011 BP 245 EP 257 D2 10.1007/978-3-7091-0198-8 PG 13 WC Parasitology SC Parasitology GA BWT49 UT WOS:000294828300017 ER PT J AU Okamoto, J Buffington, SD Cloum, HM Mendenhall, BM Toboni, M Valente, TW AF Okamoto, Janet Buffington, Sandra de Castro Cloum, Heather M. Mendenhall, Brett M. Toboni, Michael Valente, Thomas W. TI The influence of health knowledge in shaping political priorities: Examining HIV/AIDS knowledge and public opinion about global health and domestic policies SO GLOBAL PUBLIC HEALTH LA English DT Article DE HIV/AIDS; public opinion; health knowledge; global health; political priorities AB Public opinion polls have historically indicated that the US public favours domestic over global priorities. It is not known what influence health knowledge has in shaping public opinion about domestic and global health policy. This study examines how knowledge of HIV/AIDS is related to the rated importance of domestic and global health issues. Participants were recruited to participate in an electronic survey (N = 995) and were predominantly White (86.3%), married (61.9%) and female (71.8%). HIV/AIDS knowledge was significantly associated with both domestic (beta = 0.12, p < 0.05) and global health (beta = 0.14, p < 0.01) priorities after controlling for sociodemographic variables. In addition, global health was found to act as a mediator between HIV/AIDS knowledge and perceived importance of domestic issues. Study findings suggest that those with greater HIV/AIDS knowledge rate global health issues higher, which in turn affects ratings of more domestic issues. This research has implications for ways to gain support for implementation of public health policy through increasing health knowledge. C1 [Okamoto, Janet] NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. [Buffington, Sandra de Castro] USC Annenberg Norman Lear Ctr, Beverly Hills, CA 90211 USA. [Okamoto, Janet; Cloum, Heather M.; Mendenhall, Brett M.; Toboni, Michael; Valente, Thomas W.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Inst Hlth Promot & Dis Prevent Res, Alhambra, CA 91803 USA. RP Okamoto, J (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD 20892 USA. EM okamotojm@mail.nih.gov OI Okamoto, Janet/0000-0002-3164-2183 NR 30 TC 0 Z9 0 U1 1 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1744-1692 J9 GLOB PUBLIC HEALTH JI Glob. Public Health PY 2011 VL 6 IS 8 BP 830 EP 842 DI 10.1080/17441692.2010.551517 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 854RH UT WOS:000297511400003 PM 21360382 ER PT J AU Flood, A Mason, JB Liu, ZH Cash, BD Schatzkin, A Schoenfeld, PS Cross, AJ AF Flood, Andrew Mason, Joel B. Liu, Zhenhua Cash, Brooks D. Schatzkin, Arthur Schoenfeld, Philip S. Cross, Amanda J. TI Concentration of folate in colorectal tissue biopsies predicts prevalence of adenomatous polyps SO GUT LA English DT Article ID COLONIC MUCOSAL CONCENTRATIONS; ISLAND METHYLATOR PHENOTYPE; MICROSATELLITE INSTABILITY; BLOOD MEASUREMENTS; CANCER-RISK; WOMEN; ASSOCIATION; NEOPLASIA; C677T; GENE AB Background and aims Folate has been implicated as a potential aetiological factor for colorectal cancer. Previous research has not adequately exploited concentrations of folate in normal colonic mucosal biopsies to examine the issue. Methods Logistic regression models were used to estimate ORs and 95% CIs of adenoma according to the tissue concentration of folate using asymptomatic average-risk women (40-70 years) in a colorectal cancer screening study. Of the 1593 eligible women who were offered enrolment, 1483 (93%) participated. Colonoscopy was complete to the caecum in 98.7% (1463/1483) of the subjects, and normal colonic tissue biopsies were obtained from 813 (56%) of these, of whom 170 had at least one adenoma. Results A marginal reduction in risk for proximal adenomas (OR 0.56, 95% CI 0.29 to 1.09) but not distal adenomas (OR 1.01, 95% CI 0.43 to 2.37) was observed among women in the highest quintile of tissue folate concentration. A significant reduction in risk for advanced adenoma was observed for women in the highest quintile of tissue folate concentration (OR 0.24, 95% CI 0.06 to 0.93). Defining the outcome as proximal adenomatous and/or hyperplastic polyps, statistically significant inverse associations with tissue concentrations of folate were also observed (OR 0.54, 95% CI 0.31 to 0.95 for quintile 5 vs quintile 1). Conclusions These findings are consistent with the hypothesis that folate status of colonic mucosa is an exposure that is aetiologically important in determining the risk of particular molecular subtypes of colorectal cancer. C1 [Flood, Andrew] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Flood, Andrew] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Mason, Joel B.; Liu, Zhenhua] Tufts Univ, Vitamins & Carcinogenesis Lab, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Cash, Brooks D.] Uniformed Serv Univ Hlth Sci, Div Gastroenterol, Bethesda, MD 20814 USA. [Cash, Brooks D.] Natl Naval Med Ctr, Div Gastroenterol, Bethesda, MD USA. [Schatzkin, Arthur; Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Schoenfeld, Philip S.] Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI USA. [Schoenfeld, Philip S.] Vet Affairs Ctr Excellence Hlth Serv Res, Ann Arbor, MI USA. RP Flood, A (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA. EM flood009@umn.edu FU National Institutes of Health [K07 CA108910-01A1, K23-DK-60040]; American Society for Gastrointestinal Endoscopy; American College of Gastroenterology; National Cancer Institute, Bethesda, MD FX Research funded by National Institutes of Health grant K07 CA108910-01A1 (AF), National Institute of Health grant K23-DK-60040 (PSS) and an American Society for Gastrointestinal Endoscopy Career Development Award (PSS). The CONCeRN Study was funded by research grants from the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy as well as Intramural Research Program funds from the National Cancer Institute, Bethesda, MD. NR 33 TC 5 Z9 6 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JAN PY 2011 VL 60 IS 1 BP 66 EP 72 DI 10.1136/gut.2010.208074 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 692WV UT WOS:000285187500012 PM 21068136 ER PT J AU Han, JJ Yu, MS Houston, N Steinberg, SM Kohn, EC AF Han, Jasmine J. Yu, Minshu Houston, Nicole Steinberg, Seth M. Kohn, Elise C. TI Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Progranulin (PGRN); Biomarkers; Progression free survival; Overall survival; Epithelial ovarian cancer ID LEUKOCYTE PROTEASE INHIBITOR; GROWTH-FACTOR; INDUCTION CHEMOTHERAPY; CA-125 LEVELS; IN-VIVO; PRECURSOR; CARCINOMA; CELLS; ACROGRANIN; OVEREXPRESSION AB Objective. There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC. Method. PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors. Results. Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P<0.0001) and OS (P<0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC = 0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model. Conclusions. We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker. Published by Elsevier Inc. C1 [Han, Jasmine J.; Yu, Minshu; Houston, Nicole; Kohn, Elise C.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Han, Jasmine J.] NCI, Walter Reed Army Med Ctr, Gynecol Malignancies Lab, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), 10 Ctr Dr,MSC1500,Bldg 10,Room B1B51, Bethesda, MD 20892 USA. EM Kohne@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 38 TC 16 Z9 19 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2011 VL 120 IS 1 BP 5 EP 10 DI 10.1016/j.ygyno.2010.09.006 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 701NO UT WOS:000285824800002 PM 20950846 ER PT J AU Hsieh, MM Wu, CJ Tisdale, JF AF Hsieh, Matthew M. Wu, Catherine J. Tisdale, John F. TI In mixed hematopoietic chimerism, the donor red cells win SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID BONE-MARROW-TRANSPLANTATION; BETA-THALASSEMIA; INEFFECTIVE ERYTHROPOIESIS; GENE-THERAPY; LONG-TERM; DISEASE; ANEMIA; ENGRAFTMENT C1 [Hsieh, Matthew M.; Tisdale, John F.] NHLBI, Mol Clin Hematol Branch, Bethesda, MD 20824 USA. [Hsieh, Matthew M.; Tisdale, John F.] Natl Diabet Digest & Kidney Dis NIDDK, NIH, Bethesda, MD USA. [Wu, Catherine J.] Harvard Univ, Canc Vaccine Ctr, Dana Farber Canc Inst, Sch Med, Bethesda, MD USA. RP Hsieh, MM (reprint author), NHLBI, Mol Clin Hematol Branch, Bethesda, MD 20824 USA. EM johntis@nhlbi.nih.gov FU Intramural NIH HHS NR 18 TC 6 Z9 6 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2011 VL 96 IS 1 BP 13 EP 15 DI 10.3324/haematol.2010.035576 PG 3 WC Hematology SC Hematology GA 715RT UT WOS:000286902400005 PM 21193430 ER PT J AU Gordeuk, VR Minniti, CR Nouraie, M Campbell, AD Rana, SR Luchtman-Jones, L Sable, C Dham, N Ensing, G Prchal, JT Kato, GJ Gladwin, MT Castro, OL AF Gordeuk, Victor R. Minniti, Caterina R. Nouraie, Mehdi Campbell, Andrew D. Rana, Sohail R. Luchtman-Jones, Lori Sable, Craig Dham, Niti Ensing, Gregory Prchal, Josef T. Kato, Gregory J. Gladwin, Mark T. Castro, Oswaldo L. TI Elevated tricuspid regurgitation velocity and decline in exercise capacity over 22 months of follow up in children and adolescents with sickle cell anemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE sickle cell anemia; tricuspid regurgitation velocity; E/Etdi; hemolysis; six minute walk ID SOCIETY-OF-ECHOCARDIOGRAPHY; PULMONARY-ARTERY PRESSURES; 6-MINUTE WALK TEST; DISEASE PATIENTS; RISK-FACTOR; TASK-FORCE; HYPERTENSION; DEATH; MULTICENTER; GUIDELINES AB Background While in adults with sickle cell disease an elevation of tricuspid regurgitation velocity is associated with increased mortality, the importance of this finding in children has not been established. The role of intravascular hemolysis in the development of this complication is controversial. Design and Methods We conducted a prospective, longitudinal, multi-center study of 160 individuals aged 3-20 years with hemoglobin SS, performing baseline and follow-up determinations of clinical markers, six-minute walk distance less than tricuspid regurgitation velocity and E/Etdi ratio by echocardiography. Results At baseline, 14.1% had tricuspid regurgitation velocity of 2.60 m/sec or over, which suggests elevated systolic pulmonary artery pressure, and 7.7% had increased E/Etdi, which suggests elevated left ventricular filling pressure. Over a median of 22 months, baseline elevation in tricuspid regurgitation velocity was associated with an estimated 4.4-fold increase in the odds of a 10% or more decline in age-standardized six-minute-walk distance (P=0.015). During this interval, baseline values above the median for a hemolytic component derived from four markers of hemolysis were associated with a 9.0-fold increase in the odds of the new onset of elevated tricuspid regurgitation velocity (P=0.008) and baseline E/Etdi elevation was associated with an estimated 6.1-fold increase in the odds (P=0.039). In pathway analysis, higher baseline hemolytic component and E/Etdi predicted elevated tricuspid regurgitation velocity at both baseline and follow up, and these elevations in turn predicted decline in six-minute-walk distance. Conclusions Further studies should define the long-term risks of elevated tricuspid regurgitation velocity in childhood and identify potential interventions to prevent increased pulmonary artery pressure and preserve function. C1 [Gordeuk, Victor R.; Nouraie, Mehdi; Castro, Oswaldo L.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20060 USA. [Minniti, Caterina R.; Kato, Gregory J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Campbell, Andrew D.; Ensing, Gregory] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Rana, Sohail R.] Howard Univ, Dept Pediat & Child Hlth, Washington, DC 20060 USA. [Luchtman-Jones, Lori; Sable, Craig; Dham, Niti] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Prchal, Josef T.] Univ Utah, Salt Lake City, UT USA. [Prchal, Josef T.] ARUP, Salt Lake City, UT USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Vasc Med Inst, Pittsburgh, PA USA. RP Gordeuk, VR (reprint author), Howard Univ, Ctr Sickle Cell Dis, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM vgordeuk@howard.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU NHLBI [2 R25 HL003679-08, 1 R01 HL079912-02]; Howard University GCRC, NCRR, NIH, Bethesda, MD [2MOI RR10284-10]; National Institutes of Health FX Supported in part by grant ns. 2 R25 HL003679-08 and 1 R01 HL079912-02 from NHLBI, by Howard University GCRC grant n. 2MOI RR10284-10 from NCRR, NIH, Bethesda, MD, and by the intramural research program of the National Institutes of Health. NR 41 TC 31 Z9 32 U1 0 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2011 VL 96 IS 1 BP 33 EP 40 DI 10.3324/haematol.2010.030767 PG 8 WC Hematology SC Hematology GA 715RT UT WOS:000286902400008 PM 20884713 ER PT J AU Borthakur, G Kantarjian, H Ravandi, F Zhang, WG Konopleva, M Wright, JJ Faderl, S Verstovsek, S Mathews, S Andreeff, M Cortes, JE AF Borthakur, Gautam Kantarjian, Hagop Ravandi, Farhad Zhang, Weiguo Konopleva, Marina Wright, John J. Faderl, Stefan Verstovsek, Srdan Mathews, Sheela Andreeff, Michael Cortes, Jorge E. TI Phase I study of sorafenib in patients with refractory or relapsed acute leukemias SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE sorafenib; FLT3 mutation; leukemia ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FACTOR RECEPTOR INHIBITOR; FLT3 INHIBITOR; KINASE INHIBITOR; RAF KINASE; TANDEM DUPLICATION; SOLID TUMORS; AML CELLS; RESISTANCE AB Background Sorafenib is a multi-kinase inhibitor with activity against fms-like tyrosine kinase 3 with internal tandem duplication mutation and Raf kinase among others. A phase I dose escalation study of sorafenib was conducted in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias. Design and Methods Fifty patients received one of two different schedules; Schedule "A": once or twice daily, five days per week, every week for a 21 day cycle, and Schedule "B": once or twice daily, for 14 days every 21 days. Dose limiting toxicities were grade 3/4 hypertension, hyperbilirubinemia, and amylase elevation. The recommended phase II dose in hematologic malignancies is 400 mg twice daily for both schedules. Results Complete remissions or complete remissions with incomplete recovery of platelets were achieved in 5 (10%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Significant reduction in bone marrow and/or peripheral blood blasts was seen in an additional 17 (34%) patients (all with fms-like tyrosine kinase 3-internal tandem duplication). Eleven of these responses (including 3 complete remissions/complete remissions with incomplete recovery) lasted for 2 cycles or beyond. In conclusion, sorafenib is active and well tolerated in acute myelogenous leukemia with fms-like tyrosine kinase 3 internal tandem duplication mutation. Conclusions Additional studies of sorafenib in patients with acute myelogenous leukemia, particularly those with Ems-like tyrosine kinase 3 internal tandem duplication, are warranted, including sorafenib-based combinations. (ClinicalTrials.gov Identifier: NCT00217646) C1 [Borthakur, Gautam; Kantarjian, Hagop; Ravandi, Farhad; Konopleva, Marina; Faderl, Stefan; Verstovsek, Srdan; Mathews, Sheela; Andreeff, Michael; Cortes, Jorge E.] Univ Texas MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA. [Zhang, Weiguo; Konopleva, Marina; Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Cortes, JE (reprint author), Univ Texas MD Anderson Canc Ctr, Leukemia Dept, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA. EM jcortes@mdanderson.org FU NIH [U01CA062461] FX NIH Grant U01CA062461. NR 36 TC 67 Z9 70 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD JAN PY 2011 VL 96 IS 1 BP 62 EP 68 DI 10.3324/haematol.2010.030452 PG 7 WC Hematology SC Hematology GA 715RT UT WOS:000286902400012 PM 20952518 ER PT J AU Wang, GJ Volkow, ND Telang, F Thanos, PK Fowler, JS AF Wang, Gene-Jack Volkow, Nora D. Telang, Frank Thanos, Panayotis K. Fowler, Joanna S. BE Preedy, VR Watson, RR Martin, CR TI Gender Differences in Brain Activation by Food Stimulation SO HANDBOOK OF BEHAVIOR, FOOD AND NUTRITION LA English DT Article; Book Chapter ID DOPAMINE RELEASE; DORSAL STRIATUM; MENSTRUAL-CYCLE; DRUG REWARD; IN-VIVO; WOMEN; OBESITY; DIETARY; RESTRICTION; MODULATION C1 [Wang, Gene-Jack; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Volkow, Nora D.] NIDA, Off Director, Rockville, MD USA. [Telang, Frank] NIAAA, Neuroimaging Lab, Upton, NY USA. [Thanos, Panayotis K.] NIAAA, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY USA. RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 490, Upton, NY 11973 USA. EM gjwang@bnl.gov NR 35 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92270-6 PY 2011 BP 505 EP 514 DI 10.1007/978-0-387-92271-3_33 D2 10.1007/978-0-387-92271-3 PG 10 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA BDE45 UT WOS:000312946600035 ER PT J AU Shomaker, LB Tanofsky-Kraff, M Yanovski, JA AF Shomaker, Lauren B. Tanofsky-Kraff, Marian Yanovski, Jack A. BE Preedy, VR Watson, RR Martin, CR TI Disinhibited Eating and Body Weight in Youth SO HANDBOOK OF BEHAVIOR, FOOD AND NUTRITION LA English DT Article; Book Chapter ID OVERWEIGHT CHILDREN; ENERGY-INTAKE; INTERPERSONAL PSYCHOTHERAPY; DISORDERED BEHAVIORS; DIETARY RESTRAINT; OBESE ADOLESCENTS; HISPANIC CHILDREN; BULIMIC BEHAVIORS; ADULT OBESITY; RISK-FACTORS C1 [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv,Hatfield CRC, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Dept Hlth & Human Serv,Hatfield CRC, 9000 Rockvile Pike,MSC 1103,Room IE 3330, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 NR 86 TC 9 Z9 9 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-92270-6 PY 2011 BP 2183 EP 2200 DI 10.1007/978-0-387-92271-3_139 D2 10.1007/978-0-387-92271-3 PG 18 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA BDE45 UT WOS:000312946602012 ER PT S AU Vinson, C Chatterjee, R Fitzgerald, P AF Vinson, Charles Chatterjee, Raghunath Fitzgerald, Peter BE Hughes, TR TI Transcription Factor Binding Sites and Other Features in Human and Drosophila Proximal Promoters SO HANDBOOK OF TRANSCRIPTION FACTORS SE Subcellular Biochemistry LA English DT Article; Book Chapter ID DNA-BINDING; CRYSTAL-STRUCTURE; HUMAN GENOME; ETS-FAMILY; IN-VITRO; COMPLEX; METHYLATION; SEQUENCES; PROTEIN; CPG AB Eukaryotic promoters determine transcription start sites (TSSs), and are often enriched for transcription factor binding sites (TFBSs), which presumably play a major role in determining the location and activity of the TSS. In mammalian Systems, proximal promoters are enriched for the CpG dinucleotide. The TFBSs that are enriched in proximal promoters (-200 bps to the TSS) are CCAAT, ETS, NRF1, SP1, E-Box, CRE, BoxA, and TATA. Only TATA occurs in a DNA strand dependent manner. In Drosophila, proximal promoters are AT rich and many putative TFBSs are enriched in proximal promoters. These sequences are different from those that occur in human promoters, except for TATA and E-Box, and many occur on a single strand of DNA giving directionality to the promoter. Thus, fundamental differences have arisen as promoters evolved in metazoans. C1 [Vinson, Charles; Chatterjee, Raghunath] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Fitzgerald, Peter] NCI, Genome Anal Unit, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. EM Vinsonc@mail.nih.gov; chatterjeer2@mail.nih.gov; pcf@helix.nih.gov NR 46 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0306-0225 BN 978-90-481-9068-3 J9 SUBCELL BIOCHEM JI Subcell. Biochem. PY 2011 VL 52 BP 205 EP 222 DI 10.1007/978-90-481-9069-0_10 D2 10.1007/978-90-481-9069-0 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BVG87 UT WOS:000291502700010 PM 21557085 ER PT J AU Ersig, AL Hadley, DW Koehly, LM AF Ersig, Anne L. Hadley, Donald W. Koehly, Laura M. TI Understanding Patterns of Health Communication in Families at Risk for Hereditary Nonpolyposis Colorectal Cancer: Examining the Effect of Conclusive Versus Indeterminate Genetic Test Results SO HEALTH COMMUNICATION LA English DT Article ID LYNCH-SYNDROME; SOCIAL NETWORKS; MUTATIONS; INFORMATION; RELATIVES; HNPCC AB In families meeting criteria for hereditary nonpolyposis colorectal cancer (HNPCC), genetic testing may or may not identify a mutation. Communication about genetic testing and risk in families with identified HNPCC mutations is associated with individual and relational factors. Similar communication patterns would be expected in families with similar clinical and pathological characteristics, but without an identified HNPCC mutation; however, previous studies have not included such families. Social network analysis was used to compare communication networks and associated individual and relational factors in families with and without identified HNPCC mutations. Respondents from families without identified mutations communicated about genetic counseling and testing and risk for HNPCC with a significantly smaller proportion of network members, compared to respondents from mutation-positive families. Members of families without identified mutations were also more likely to share thoughts about risk for HNPCC with network members whose advice they take, compared to members of families with known mutations. These findings extend our knowledge of communication in families at risk of HNPCC to include the many families in which a causative mutation has not yet been identified. Differences in the breadth of communication about genetics and risk for HNPCC, and the possibility that members of families without identified mutations may seek advice from those with whom they communicate about risk, provide new avenues for future research. Understanding existing communication patterns could help improve education and counseling processes, and facilitate the development of interventions designed to assist in family discussions of risk. C1 [Ersig, Anne L.] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. [Ersig, Anne L.] NINR, NIH, Bethesda, MD 20892 USA. [Ersig, Anne L.; Hadley, Donald W.; Koehly, Laura M.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Ersig, AL (reprint author), Univ Iowa, Coll Nursing, Room 334 CNB,50 Newton Rd, Iowa City, IA 52242 USA. EM anne-ersig@uiowa.edu FU Intramural NIH HHS [Z01 HG200335-03, ZIA HG200335-05]; NHGRI NIH HHS [Z01HG200335-01, Z01 HG200335] NR 32 TC 8 Z9 8 U1 3 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1041-0236 EI 1532-7027 J9 HEALTH COMMUN JI Health Commun. PY 2011 VL 26 IS 7 BP 587 EP 594 DI 10.1080/10410236.2011.558338 PG 8 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 882MP UT WOS:000299568100001 PM 21512927 ER PT S AU Ramsden, CE Hibbeln, JR Majchrzak-Hong, SF AF Ramsden, Christopher E. Hibbeln, Joseph R. Majchrzak-Hong, Sharon F. BE Simopoulos, AP TI All PUFAs Are Not Created Equal: Absence of CHD Benefit Specific to Linoleic Acid in Randomized Controlled Trials and Prospective Observational Cohorts SO HEALTHY AGRICULTURE, HEALTHY NUTRITION, HEALTHY PEOPLE SE World Review of Nutrition and Dietetics LA English DT Proceedings Paper; Book Chapter CT Inaugural Conference of the World-Council-on-Genetic-Nutrition-and-Fitness-for-Health CY OCT 05-08, 2010 CL Olympia, GREECE SP Minist Hlth & Social Solidar, Hellen Sports Res Inst, Olymp Athlet Ctr Athens, Greek Org Football Prognost SA, Nutrilite Hlth Inst, Hellen Amer Univ, Hellen Amer Union, Int Union Nutr Sci, Int Soc Nutrigent, Nutrgenom ID CORONARY-HEART-DISEASE; ESTROGEN REPLACEMENT THERAPY; POLYUNSATURATED FATTY-ACIDS; DIETARY-FAT; FOLLOW-UP; CARDIOVASCULAR-DISEASE; ADIPOSE-TISSUE; UNITED-STATES; RISK; WOMEN C1 [Ramsden, Christopher E.; Hibbeln, Joseph R.; Majchrzak-Hong, Sharon F.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Ramsden, CE (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, 31 Ctr Dr,Bldg 31,Room, Bethesda, MD 20892 USA. EM chris.ramsden@nih.gov FU Intramural NIH HHS [ZIA AA000115-11] NR 44 TC 10 Z9 11 U1 0 U2 3 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-8055-9779-1 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2011 VL 102 BP 30 EP 43 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BWP47 UT WOS:000294441100006 PM 21865817 ER PT B AU Maltsev, VA Vinogradova, TM Lakatta, EG AF Maltsev, Victor A. Vinogradova, Tatiana M. Lakatta, Edward G. BE Tripathi, ON Ravens, U Sanguinetti, MC TI Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins SO HEART RATE AND RHYTHM: MOLECULAR BASIS, PHARMACOLOGICAL MODULATION AND CLINICAL IMPLICATIONS LA English DT Article; Book Chapter ID RABBIT SINOATRIAL NODE; SUBSARCOLEMMAL CA2+ RELEASES; NA+-CA2+ EXCHANGE CURRENT; SPONTANEOUS BEATING RATE; CAT RIGHT ATRIUM; DIASTOLIC DEPOLARIZATION; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTOR; CELL AUTOMATICITY; HEARTS PACEMAKER C1 [Maltsev, Victor A.; Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Maltsev, VA (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM MaltsevVi@grc.nia.nih.gov NR 53 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-3-642-17574-9 PY 2011 BP 83 EP 99 DI 10.1007/978-3-642-17575-6_4 D2 10.1007/978-3-642-17575-6 PG 17 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy; Toxicology SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy; Toxicology GA BVJ55 UT WOS:000291666400004 ER PT J AU Burns, KM Evans, F Kaltman, JR AF Burns, Kristin M. Evans, Frank Kaltman, Jonathan R. TI Pediatric ICD utilization in the United States from 1997 to 2006 SO HEART RHYTHM LA English DT Article DE Implantable cardioverter-defibrillator; Pediatric; Congenital heart disease; Administrative data; Population-based data ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CONGENITAL HEART-DISEASE; CONTEMPORARY CLINICAL STANDARDS; NATIONAL ADMINISTRATIVE DATA; SURGICAL MORTALITY-RATES; SUDDEN CARDIAC DEATH; THERAPY; COMPLICATIONS; POPULATION AB BACKGROUND Indications for implantable cardioverter-defibrillator (ICD) implantation in children have expanded, yet pediatric population-based data on ICD implantation are lacking. OBJECTIVE We characterized trends in pediatric ICD use in the United States from 1997 to 2006. METHODS We examined national hospital administrative data from the 1997, 2000, 2003, and 2006 Kids' Inpatient Database (KID) for new ICD implants in patients younger than 18 years of age and characterized patients, hospitals, and hospitalization-related outcomes. RESULTS The number of pediatric ICD implants per year increased 3-fold (from 130 in 1997 to 396 in 2006, P = .003). Implants with a concomitant diagnosis of life-threatening arrhythmia decreased from 77% to 45% (P = .001). The average age decreased from 13.6 to 12.2 years (P = .01), and the percentage of patients younger than 5 years of age tended to increase (up to 10%, P = .09). In 2006, the number of implants per center ranged from 1 to 24 (median 3). Over time, the complication rate tended to decrease (from 16 to 10%, P = .07). Complication rate was not related to a diagnosis of congenital heart disease, age, or implant volume. CONCLUSION ICD use increased dramatically in children from 1997 to 2006, although implantation declined in patients with a concomitant diagnosis of life-threatening arrhythmia (those likely to undergo implantation for secondary prevention). The complication rate tended to decrease overall. Each center implants relatively few ICDs per year, which may have implications for competency and training. C1 [Burns, Kristin M.] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Burns, Kristin M.; Kaltman, Jonathan R.] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Burns, KM (reprint author), NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 8215, Bethesda, MD 20892 USA. EM kristin.burns@nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 33 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2011 VL 8 IS 1 BP 23 EP 28 DI 10.1016/j.hrthm.2010.09.073 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 698VW UT WOS:000285622700007 PM 20887811 ER PT J AU Magnani, JW Gorodeski, EZ Johnson, VM Sullivan, LM Hamburg, NM Benjamin, EJ Ellinor, PT AF Magnani, Jared W. Gorodeski, Eiran Z. Johnson, Victor M. Sullivan, Lisa M. Hamburg, Naomi M. Benjamin, Emelia J. Ellinor, Patrick T. TI P wave duration is associated with cardiovascular and all-cause mortality outcomes: the National Health and Nutrition Examination Survey SO HEART RHYTHM LA English DT Article DE Electrocardiography; Epidemiology; mortality; Risk factors; NHANES; P waves ID CONGESTIVE-HEART-FAILURE; LONG QT SYNDROME; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; DISPERSION; STROKE; RISK; POPULATION; AGE AB BACKGROUND P wave indices are an intermediate phenotype modulated by atrial conduction and electrophysiology. Their clinical correlates and association with all-cause mortality have received limited scrutiny. OBJECTIVE To determine the relationship between P wave indices and cardiovascular and all-cause mortality in the National Health and Nutrition Examination Survey (NHANES), a highly representative United States sample. METHODS NHANES III (1988-1994) quantified PR interval and P wave duration and amplitude. Mortality data through 2006 were obtained from National Death Index (NDI) records. RESULTS Of 8,561 subjects with electrocardiograms (ECGs), 7,486 (mean age 60.0 +/- 13.3 years., 51.9% women, 50.1% ethnic minorities) had ECGs in sinus rhythm, linked mortality data, and complete assessments. Over a median 8.6-year follow-up (range 0.1-12.2 years), there were 679 cardiovascular deaths and 1,559 all-cause mortality deaths. Older age, male sex, and higher body mass index were significantly associated with greater PR interval and P wave duration and with lower P wave amplitude. African Americans had higher mean values of all three P wave indices. In a multivariable model adjusting for cardiovascular risk factors, P wave duration was the only P wave index significantly associated with cardiovascular mortality (hazard ratio [HR] 1.13, per 1 standard deviation [SD], 95% confidence interval [CI] 1.04 -1.23; P = 004) and all-cause mortality (HR 1.06 per 1 SD; 95% CI 1.00-1.13; P = .050). CONCLUSIONS In a highly representative U. S. sample, P wave duration was significantly associated with increased cardiovascular and all-cause mortality. P wave duration may reflect subclinical disease and merits elucidation as a marker of risk for adverse outcomes. C1 [Magnani, Jared W.; Hamburg, Naomi M.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Gorodeski, Eiran Z.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu OI Hamburg, Naomi/0000-0001-5504-5589; Gorodeski, Eiran/0000-0003-3756-8831; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF2190028]; National Institutes of Health [RC1HL101056, HL092577] FX This research was funded by American Heart Association Award 09FTF2190028 and by grants from the National Institutes of Health (RC1HL101056; HL092577). NR 40 TC 29 Z9 30 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JAN PY 2011 VL 8 IS 1 BP 93 EP 100 DI 10.1016/j.hrthm.2010.09.020 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 698VW UT WOS:000285622700020 PM 20868770 ER PT J AU Abdalla, MY Fawzi, M Al-Maloul, SR El-Banna, N Tayyem, RF Ahmad, IM AF Abdalla, Maher Y. Fawzi, Mohammad Al-Maloul, Salem R. El-Banna, Nasser Tayyem, Reema F. Ahmad, Iman M. TI INCREASED OXIDATIVE STRESS AND IRON OVERLOAD IN JORDANIAN beta-THALASSEMIC CHILDREN SO HEMOGLOBIN LA English DT Article DE Oxidative stress; Thalassemia; Glutathione (GSH); thiobarbituric acid reactive substances (TBARS) ID ANTIOXIDANT STATUS; LIPID-PEROXIDATION; HUMAN ERYTHROCYTES; HYDROGEN-PEROXIDE; CELL MEMBRANE; DISEASE; MALONDIALDEHYDE; HEMOGLOBIN; CATALASE; INJURY AB beta-Thalassemia (beta-thal) is associated with abnormal synthesis of hemoglobin (Hb). Repeated blood transfusions in patients with beta-thal major (beta-TM) leads to an enhanced generation of reactive oxygen species (ROS), and subjects patients to peroxidative injury. We studied the antioxidant status and oxidative damage to children with beta-thal in Jordan. Samples from 40 children with beta-thal and 40 healthy controls were used. All children were under 13 years of age. Our results showed that plasma thiobarbituric acid reactive substances (TBARS) were elevated in beta-thalassemic children compared to controls together with compensatory increase in superoxide dismutase (SOD) activity and decrease in catalase (CAT) activity. Elevated serum ferritin showed positive correlation with elevated liver enzyme levels except gamma glutamyl transferase (GGT), confirming liver involvement due to iron overload. Serum ferritin also showed a positive correlation with elevated TBARS and SOD, suggesting that iron overload is involed in the oxidative stress shown in cells. C1 [Abdalla, Maher Y.; Fawzi, Mohammad; Al-Maloul, Salem R.] Hashemite Univ, Dept Biol Sci & Biotechnol, Zarqa, Jordan. [El-Banna, Nasser] Hashemite Univ, Dept Clin Nutr & Dietet, Zarqa, Jordan. [Tayyem, Reema F.] Hashemite Univ, Dept Med Lab Sci, Zarqa, Jordan. [Ahmad, Iman M.] Hashemite Univ, Dept Radiog, Zarqa, Jordan. RP Abdalla, MY (reprint author), NCI, Ctr Canc Res, Natl Naval Med Ctr, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM Abdallamy@mail.nih.gov RI tayyem, reema/I-1217-2016 OI tayyem, reema/0000-0003-1640-0511 FU Hashemite University, Zarqa, Jordan FX This study was supported by a grant from The Deanship of Research and Graduate Studies, The Hashemite University, Zarqa, Jordan. NR 55 TC 12 Z9 14 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0363-0269 J9 HEMOGLOBIN JI Hemoglobin PY 2011 VL 35 IS 1 BP 67 EP 79 DI 10.3109/03630269.2010.544624 PG 13 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA 737ZQ UT WOS:000288609500008 PM 21250883 ER PT J AU Thomas, E Feld, JJ Li, QS Hu, ZY Fried, MW Liang, TJ AF Thomas, Emmanuel Feld, Jordan J. Li, Qisheng Hu, Zongyi Fried, Michael W. Liang, T. Jake TI Ribavirin Potentiates Interferon Action by Augmenting Interferon-Stimulated Gene Induction in Hepatitis C Virus Cell Culture Models SO HEPATOLOGY LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; PLUS RIBAVIRIN; STELLATE CELLS; PROTEASOME INHIBITORS; PEGYLATED INTERFERON; ANTIVIRAL ACTIVITY; VIRAL-INFECTION; PEGINTERFERON; EXPRESSION; RNA AB The combination of pegylated interferon (PEG-IFN) and ribavirin is the standard treatment for chronic hepatitis C. Our recent clinical study suggests that ribavirin augments the induction of interferon-stimulated genes (ISGs) in patients treated for hepatitis C virus (HCV) infection. In order to further characterize the mechanisms of action of ribavirin, we examined the effect of ribavirin treatment on ISG induction in cell culture. In addition, the effect of ribavirin on infectious HCV cell culture systems was studied. Similar to interferon (IFN)-alpha, ribavirin potently inhibits JFH-1 infection of Huh7.5.1 cells in a dose-dependent manner, which spans the physiological concentration of ribavirin in vivo. Microarray analysis and subsequent quantitative polymerase chain reaction assays demonstrated that ribavirin treatment resulted in the induction of a distinct set of ISGs. These ISGs, including IFN regulatory factors 7 and 9, are known to play an important role in anti-HCV responses. When ribavirin is used in conjunction with IFN-alpha, induction of specific ISGs is synergistic when compared with either drug applied separately. Direct up-regulation of these antiviral genes by ribavirin is mediated by a novel mechanism different from those associated with IFN signaling and intracellular double-stranded RNA sensing pathways such as RIG-I and MDA5. RNA interference studies excluded the activation of the Toll-like receptor and nuclear factor kappa B pathways in the action of ribavirin. Conclusion: Our study suggests that ribavirin, acting by way of a novel innate mechanism, potentiates the anti-HCV effect of IFN. Understanding the mechanism of action of ribavirin would be valuable in identifying novel antivirals (HEPATOLOGY 2011;53:32-41) C1 [Thomas, Emmanuel; Feld, Jordan J.; Li, Qisheng; Hu, Zongyi; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Feld, Jordan J.] Toronto Western Hosp, Ctr Liver, Div Gastroenterol, Dept Med, Toronto, ON M5T 2S8, Canada. [Fried, Michael W.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,9B17, Bethesda, MD 20892 USA. EM jakel@bdg10.niddk.nih.gov RI Li, Qisheng/K-1909-2013 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; National Institutes of Health [DK066144] FX Supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and in part by a National Institutes of Health K24 mentoring award DK066144 (to M. W. F.). NR 62 TC 93 Z9 96 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2011 VL 53 IS 1 BP 32 EP 41 DI 10.1002/hep.23985 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 709AB UT WOS:000286406300006 PM 21254160 ER PT J AU Banaudha, K Kaliszewski, M Korolnek, T Florea, L Yeung, ML Jeang, KT Kumar, A AF Banaudha, Krishna Kaliszewski, Michael Korolnek, Tamara Florea, Liliana Yeung, Man Lung Jeang, Kuan-Teh Kumar, Ajit TI MicroRNA Silencing of Tumor Suppressor DLC-1 Promotes Efficient Hepatitis C Virus Replication in Primary Human Hepatocytes SO HEPATOLOGY LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; GTPASE-ACTIVATING PROTEIN; LIVER-CANCER; CELL-GROWTH; EXPRESSION; INFECTION; TARGETS; GENE; MODULATION; GENOME AB MicroRNAs (miRNAs) are approximately 22-nucleotide noncoding RNAs that constitute silencers of target gene expression. Aberrant expression of miRNA has been linked to a variety of cancers, including hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) infection is considered a major cause of chronic liver disease and HCC, although the mechanism of virus infection associated hepatocarcinogenesis remains unclear. We report a direct role of miRNAs induced in HCV-infected primary human hepatocytes that target the tumor suppressor gene DLC-1 (a Rho GTPase-activating protein), which is frequently deleted in HCC, and other solid human tumors. MicroRNA miR-141 that targets DLC-1 was accentuated in cells infected with HCV genotypes 1a, 1b, and 2a. We present several lines of evidence that efficient HCV replication requires miR-141 mediated suppression of DLC-1. An increase in miR-141 correlated with the inhibition of DLC-1 protein in HCV-infected cells. Depletion of miR-141 with oligonucleotides complementary to the miRNAs inhibited virus replication, whereas artificially increased levels of intracellular miR-141 enhanced HCV replication. HCV-infected hepatocytes showed enhanced cell proliferation that can be countered by overexpression of DLC-1. Conclusion: The collective results of this study suggest a novel mechanism of HCV infection associated miRNA-mediated regulation of a tumor suppressor protein that has the ability to influence cell proliferation and HCV infection mediated liver cancer. (HEPATOLOGY 2011;53:53-61) C1 [Kumar, Ajit] George Washington Univ, Sch Med, Dept Mol Biol, Washington, DC 20037 USA. [Banaudha, Krishna; Kaliszewski, Michael; Korolnek, Tamara; Kumar, Ajit] George Washington Univ, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Florea, Liliana] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Yeung, Man Lung] Univ Hong Kong, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China. [Jeang, Kuan-Teh] NIAID, NIH, Mol Virol Sect, Bethesda, MD 20892 USA. RP Kumar, A (reprint author), George Washington Univ, Sch Med, Dept Mol Biol, Ross Hall,Room 232,2300 Eye St NW, Washington, DC 20037 USA. EM akumar@gwu.edu RI Jeang, Kuan-Teh/A-2424-2008 NR 34 TC 47 Z9 51 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2011 VL 53 IS 1 BP 53 EP 61 DI 10.1002/hep.24016 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 709AB UT WOS:000286406300008 PM 20967756 ER PT J AU Zhang, Z Zhang, SY Zou, ZS Shi, JF Zhao, JJ Fan, R Qin, EQ Li, BS Li, ZW Xu, XS Fu, JL Zhang, JY Gao, B Tian, ZG Wang, FS AF Zhang, Zheng Zhang, Shuye Zou, Zhengsheng Shi, Jianfei Zhao, Juanjuan Fan, Rong Qin, Enqiang Li, Baosen Li, Zhiwei Xu, Xiangsheng Fu, Junliang Zhang, Jiyuan Gao, Bin Tian, Zhigang Wang, Fu-Sheng TI Hypercytolytic Activity of Hepatic Natural Killer Cells Correlates With Liver Injury in Chronic Hepatitis B Patients SO HEPATOLOGY LA English DT Article ID INTRAHEPATIC NK CELLS; C VIRUS-INFECTION; T-CELLS; GENOMIC ANALYSIS; VIRAL-HEPATITIS; HBV INFECTION; HOST RESPONSE; DAMAGE; IMMUNOPATHOGENESIS; INTERFERON AB Natural killer (NK) cells are abundant in the liver and serve as a major innate immune component against microbial infection. Although NK cells have been implicated in inducing hepatocellular damage in patients with chronic hepatitis virus infections, the roles that hepatic NK cells play in chronic hepatitis B virus (HBV) infections remain obscure. In this study, we comprehensively characterized intrahepatic and peripheral NK cells and investigated their impact on liver pathology in a cohort of HBV-infected individuals; this cohort included 51 immune-activated (IA) patients, 27 immune-tolerant (IT) carriers, and 26 healthy subjects. We found that NK cells expressing NK receptors (activation receptors) preferentially accumulated in the livers of IA patients, in which they were activated and skewed toward cytolytic activity but without a concomitant increase in interferon-gamma production, in comparison with those of IT carriers and healthy subjects. Further analysis showed that the livers of IA patients, in comparison with those of IT and healthy subjects, expressed higher levels of interleukin-12 (IL-12), IL-15, and IL-18 in situ and lower levels of IL-10, which in vitro can induce the activation and degranulation of NK cells from healthy individuals. Finally, hepatic NK cells displayed more cytolytic activity than peripheral NK cells, and this was found to be positively correlated with the liver histological activity index and serum alanine aminotransferase levels in these IA patients. Conclusion: In IA patients, hepatic NK cells are activated and preferentially skew toward cytolytic activity, which depends on an imbalanced cytokine milieu and correlates with liver injury during chronic HBV infection. (HEPATOLOGY 2011;53:73-85) C1 [Zhang, Zheng; Zhang, Shuye; Shi, Jianfei; Zhao, Juanjuan; Xu, Xiangsheng; Fu, Junliang; Zhang, Jiyuan; Wang, Fu-Sheng] Beijing 302 Hosp, Res Ctr Biol Therapy, Beijing 100039, Peoples R China. [Zou, Zhengsheng; Fan, Rong; Qin, Enqiang; Li, Baosen; Li, Zhiwei] Beijing 302 Hosp, Dept Infect Dis, Beijing 100039, Peoples R China. [Gao, Bin] NIAAA, NIH, Lab Liver Dis, Bethesda, MD USA. [Tian, Zhigang] Univ Sci & Technol China, Inst Immunol, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Peoples R China. [Tian, Zhigang] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Peoples R China. RP Wang, FS (reprint author), Beijing 302 Hosp, Res Ctr Biol Therapy, 100 Xi Si Huan Middle Rd, Beijing 100039, Peoples R China. EM fswang@public.bta.net.cn RI Tian, Zhigang/J-3512-2013 FU National Grand Program on Key Infectious Diseases [2009ZX10004-309, 2008ZX10002-007, 2008ZX10002-005-6]; National Key Basic Research Program of China [2007CB512805, 2007CB512804, 2009CB522507]; National Natural Science Foundation of China [30730088, 30972752] FX Supported by This study was supported by the National Grand Program on Key Infectious Diseases (grants 2009ZX10004-309, 2008ZX10002-007, and 2008ZX10002-005-6), the National Key Basic Research Program of China (grants 2007CB512805, 2007CB512804, and 2009CB522507), the Key Program of the National Natural Science Foundation of China (grant 30730088), and the National Natural Science Foundation of China (grant 30972752). NR 36 TC 69 Z9 85 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2011 VL 53 IS 1 BP 73 EP 85 DI 10.1002/hep.23977 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 709AB UT WOS:000286406300010 PM 21254163 ER PT J AU Tam, J Liu, J Mukhopadhyay, B Cinar, R Godlewski, G Kunos, G AF Tam, Joseph Liu, Jie Mukhopadhyay, Bani Cinar, Resat Godlewski, Grzegorz Kunos, George TI Endocannabinoids in Liver Disease SO HEPATOLOGY LA English DT Review ID CANNABINOID CB1 RECEPTOR; FATTY-ACID SYNTHESIS; ISCHEMIA-REPERFUSION INJURY; ACTIVATED PROTEIN-KINASE; HEPATIC STELLATE CELLS; DIET-INDUCED OBESITY; ENDOGENOUS CANNABINOIDS; METABOLIC SYNDROME; CIRRHOTIC RATS; ENERGY-BALANCE AB Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and it is present in both brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases and contributes to the underlying pathologies. In patients with cirrhosis of various etiologies, the activation of vascular and cardiac CB(1) receptors by macrophage-derived and platelet-derived endocannabinoids contributes to the vasodilated state and cardiomyopathy, which can be reversed by CB(1) blockade. In mouse models of liver fibrosis, the activation of CB, receptors on hepatic stellate cells is fibrogenic, and CB(1) blockade slows the progression of fibrosis. Fatty liver induced by a high-fat diet or chronic alcohol feeding depends on the activation of peripheral receptors, including hepatic CB(1) receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB(1) blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB(1) antagonists. (HEPATOLOGY 2011;53:346-355) C1 [Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George] NIAAA, NIH, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI CINAR, Resat/E-5755-2010; Ji, Haofeng/G-6206-2012 OI CINAR, Resat/0000-0002-8597-7253; FU Intramural NIH HHS [ZIA AA000350-10] NR 107 TC 65 Z9 69 U1 0 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2011 VL 53 IS 1 BP 346 EP 355 DI 10.1002/hep.24077 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 709AB UT WOS:000286406300036 PM 21254182 ER PT S AU Sun, P Tropea, JE Waugh, DS AF Sun, Ping Tropea, Joseph E. Waugh, David S. BE Evans, TC Xu, MQ TI Enhancing the Solubility of Recombinant Proteins in Escherichia coli by Using Hexahistidine-Tagged Maltose-Binding Protein as a Fusion Partner SO HETEROLOGOUS GENE EXPRESSION IN E COLI: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Maltose-binding protein; MBP; solubility enhancer; His tag; His(6)-MBP; Gateway cloning; TEV protease; tobacco etch virus protease ID SOLUBLE-PROTEIN; AFFINITY TAGS; EXPRESSION; PURIFICATION; VECTORS; SCALE AB In the field of biotechnology, fusing recombinant proteins to highly soluble partners is a common practice for overcoming aggregation in Escherichia coli. E. coli maltose-binding protein (MBP) has been recognized as one of the most effective solubilizing agents, having frequently been observed to improve the yield, enhance the solubility, and promote the proper folding of its fusion partners. The use of a dual hexahistidine-maltose-binding protein affinity tag (His(6)-MBP) has the additional advantage of allowing the fusion protein to be purified by immobilized metal affinity chromatography (IMAC) instead of or in addition to amylose affinity chromatography. This chapter describes a generic method for the overproduction of combinatorially tagged His(6)-MBP fusion proteins in E. coli, with particular emphasis on the use of recombinational cloning to construct expression vectors. In addition, simple methods for evaluating the solubility of the fusion protein and the passenger protein after it is cleaved from the dual His(6)-MBP tag are presented. C1 [Sun, Ping; Tropea, Joseph E.; Waugh, David S.] Natl Canc Inst Frederick, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD USA. RP Sun, P (reprint author), Natl Canc Inst Frederick, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD USA. FU Intramural NIH HHS NR 18 TC 28 Z9 30 U1 3 U2 15 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-966-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 705 BP 259 EP 274 DI 10.1007/978-1-61737-967-3_16 D2 10.1007/978-1-61737-967-3 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BSU97 UT WOS:000285851100016 PM 21125392 ER PT B AU Schiller, JT Lowy, DR AF Schiller, John T. Lowy, Douglas R. BE Plotkin, SA TI Developmental History of HPV Prophylactic Vaccines SO HISTORY OF VACCINE DEVELOPMENT LA English DT Article; Book Chapter ID VIRUS-LIKE PARTICLES; HUMAN-PAPILLOMAVIRUS TYPE-16; COTTONTAIL RABBIT PAPILLOMAVIRUS; RANDOMIZED CONTROLLED-TRIAL; YOUNG-WOMEN; L1 PROTEIN; IN-VITRO; DOUBLE-BLIND; CERVICAL-CARCINOMA; ADULT VOLUNTEERS C1 [Schiller, John T.] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Lowy, Douglas R.] NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov NR 63 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1338-8 PY 2011 BP 265 EP 284 DI 10.1007/978-1-4419-1339-5_27 D2 10.1007/978-1-4419-1339-5 PG 20 WC Immunology SC Immunology GA BVF18 UT WOS:000291365000027 ER PT B AU Kapikian, AZ AF Kapikian, Albert Z. BE Plotkin, SA TI History of Rotavirus Vaccines Part I: RotaShield SO HISTORY OF VACCINE DEVELOPMENT LA English DT Article; Book Chapter ID TETRAVALENT RHESUS-HUMAN; NEONATAL CALF DIARRHEA; IMMUNE ELECTRON-MICROSCOPY; YOUNG-CHILDREN; BOVINE ROTAVIRUS; VENEZUELAN INFANTS; ANTIGENIC RELATIONSHIPS; NEUTRALIZING ANTIBODY; ACUTE GASTROENTERITIS; QUADRIVALENT VACCINE C1 NIAID, Infect Dis Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kapikian, AZ (reprint author), NIAID, Infect Dis Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM akapikian@niaid.nih.gov NR 130 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1338-8 PY 2011 BP 285 EP 314 DI 10.1007/978-1-4419-1339-5_28 D2 10.1007/978-1-4419-1339-5 PG 30 WC Immunology SC Immunology GA BVF18 UT WOS:000291365000028 ER PT J AU Bernard, NF Melendez-Pena, C Kamya, P Tsoukas, CM Boulassel, MR Routy, JP Thomas, R Cote, P Kovacs, C Migueles, SA Connors, M Potter, M Harris, M Tremblay, CL AF Bernard, Nicole F. Melendez-Pena, Carlos Kamya, Philomena Tsoukas, Christos M. Boulassel, Mohamed-Rachid Routy, Jean-Pierre Thomas, Rejean Cote, Pierre Kovacs, Colin Migueles, Stephen A. Connors, Mark Potter, Martin Harris, Marianne Tremblay, Cecile L. CA Canadian Cohort HIV Infected Slow BE Aghdassi, E TI Natural Killer Cells from HIV Infected Slow Progressors Who Carry the Protective HLA-B*27 Allele and Inhibitory KIR3DL1 Receptors Have Elevated Poly-Functional Potential Compared to Bw6 Homozygotes SO HIV INFECTION IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL TREATMENT AND SOME OF ITS ASSOCIATED COMPLICATIONS LA English DT Article; Book Chapter ID MHC CLASS-I; CD8(+) T-CELLS; NK CELLS; HLA-B; ANTIRETROVIRAL THERAPY; ACTIVATING RECEPTORS; ESCAPE MUTATIONS; DENDRITIC CELLS; VIRUS; CYTOTOXICITY C1 [Bernard, Nicole F.; Melendez-Pena, Carlos; Kamya, Philomena; Tsoukas, Christos M.; Routy, Jean-Pierre; Potter, Martin] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. [Bernard, Nicole F.; Melendez-Pena, Carlos; Kamya, Philomena; Tsoukas, Christos M.] McGill Univ, Div Expt Med, Clin Quartier, Montreal, PQ, Canada. [Bernard, Nicole F.; Tsoukas, Christos M.] McGill Univ, Ctr Hlth, Div Clin Immunol & Allergy, Montreal, PQ, Canada. [Boulassel, Mohamed-Rachid; Routy, Jean-Pierre] Royal Victoria Hosp, Immunodeficiency Serv, Montreal, PQ, Canada. [Boulassel, Mohamed-Rachid; Routy, Jean-Pierre] Royal Victoria Hosp, Div Hematol, Montreal, PQ, Canada. [Boulassel, Mohamed-Rachid; Routy, Jean-Pierre] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Thomas, Rejean] Clin Actuel, Montreal, PQ, Canada. [Cote, Pierre] Clin Quartier Latin, Montreal, PQ, Canada. [Kovacs, Colin] Maple Leaf Med Clin, Toronto, ON, Canada. [Migueles, Stephen A.; Connors, Mark] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Harris, Marianne] Univ British Columbia, St Pauls Hosp, AIDS Res Program, Vancouver, BC V5Z 1M9, Canada. [Tremblay, Cecile L.] Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ, Canada. RP Bernard, NF (reprint author), McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. NR 65 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-701-7 PY 2011 BP 193 EP 212 D2 10.5772/1752 PG 20 WC Infectious Diseases SC Infectious Diseases GA BE6JN UT WOS:000374247800012 ER PT S AU Dufau, ML Sato, H Gutti, R Tsai-Morris, CH AF Dufau, Maria L. Sato, Hisashi Gutti, Ravi Tsai-Morris, Chon-Hwa BE New, MI Simpson, JL TI Gonadotropin-Regulated Testicular Helicase (GRTH/DDX25): A Master Post-transcriptional Regulator of Spermatogenesis SO HORMONAL AND GENETIC BASIS OF SEXUAL DIFFERENTIATION DISORDERS AND HOT TOPICS IN ENDOCRINOLOGY SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 2nd World Conference on Hormonal and Genetic Basis of Sexual Differentiation CY JAN 15, 2010 CL Miami, FL SP Endocrine Soc, Univ Miami, Miller Sch Med ID RNA HELICASE; CHROMATOID BODY; GENE; EXPRESSION; TRANSLATION; TESTIS C1 [Dufau, Maria L.; Sato, Hisashi; Gutti, Ravi; Tsai-Morris, Chon-Hwa] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Mol Endocrinol, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Mol Endocrinol, NIH, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov; satos@mail.nih.gov; guttir@mail.nih.gov; morrisch@mail.nih.gov OI Gutti, Ravi/0000-0002-0912-5796 FU Intramural NIH HHS NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4419-8001-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 707 BP 23 EP 29 DI 10.1007/978-1-4419-8002-1_6 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BFZ11 UT WOS:000321936100006 PM 21691948 ER PT J AU Geffner, ME Patel, K Miller, TL Hazra, R Silio, M Van Dyke, RB Borkowsky, W Worrell, C DiMeglio, LA Jacobson, DL AF Geffner, Mitchell E. Patel, Kunjal Miller, Tracie L. Hazra, Rohan Silio, Margarita Van Dyke, Russell B. Borkowsky, William Worrell, Carol DiMeglio, Linda A. Jacobson, Denise L. CA Pediat HIV AIDS Cohort Study TI Factors Associated with Insulin Resistance among Children and Adolescents Perinatally Infected with HIV-1 in the Pediatric HIV/AIDS Cohort Study SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Article DE Insulin resistance; HIV; Highly active antiretroviral therapy; Homeostatic model assessment of insulin resistance ID ACTIVE ANTIRETROVIRAL THERAPY; GLUCOSE-HOMEOSTASIS; METABOLIC SYNDROME; RISK-FACTORS; PREVALENCE; HAART; YOUTH AB Background/Aims: Because of prior inconsistent findings, we studied a large cohort of HIV-infected children to determine: (1) prevalence of insulin resistance (IR); (2) anthropometric and clinical correlates of IR, and (3) concomitant abnormalities of glucose tolerance. Methods: The study population consisted of 451 children from the Pediatric HIV/AIDS Cohort Study. The outcome of interest was HOMA-IR. Covariates included demographic, metabolic, growth, body composition, HIV laboratory tests, and treatment characteristics. Children meeting triggers for IR underwent oral glucose tolerance tests and hemoglobin A1c (HbA1c) measurements. Results: Among 402 children with glucose and insulin measurements, 15.2% had IR of whom 79% were pubertal. IR was associated with higher alanine aminotransferase, body mass index, and nadir CD4%, Tanner stage 5, and ever having received amprenavir. Of those with IR, three had impaired fasting glucose (IFG), three impaired glucose tolerance (IGT), one IFG and IGT, none diabetic glucose tolerance, and three HbA1c between 6.1 and 6.5%. Conclusion: In our cohort of HIV-infected adolescents, we observed a 15.2% prevalence of IR more closely linked to obesity than any other variable. This finding mirrors the high prevalence of obesity-mediated IR in American youth. However, associations with CD4 count and use of protease inhibitors may indicate some effect of HIV and/or its treatment. Copyright (C) 2011 S. Karger AG, Basel C1 [Geffner, Mitchell E.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Patel, Kunjal] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Patel, Kunjal; Jacobson, Denise L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Miller, Tracie L.] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA. [Hazra, Rohan; Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. [Silio, Margarita; Van Dyke, Russell B.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. [Borkowsky, William] NYU, Langone Med Ctr, New York, NY USA. [DiMeglio, Linda A.] Indiana Univ Sch Med, Dept Pediat, Div Endocrinol, Indianapolis, IN USA. RP Geffner, ME (reprint author), Childrens Hosp Los Angeles, Saban Res Inst, 4650 Sunset Blvd,Mailstop 61, Los Angeles, CA 90027 USA. EM mgeffner@chla.usc.edu OI DiMeglio, Linda/0000-0002-8033-6078 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; National Institute of Allergy and Infectious Diseases; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; National Institute of Deafness and Other Communication Disorders; National Heart Lung and Blood Institute; National Institute on Alcohol Abuse and Alcoholism; Harvard University School of Public Health [HD052102]; Tulane University School of Medicine [HD052104] FX We thank the children and families for their participation in the PHACS Adolescent Master Protocol (AMP), and the individuals and institutions involved in the conduct of PHACS AMP. The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute of Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, and the National Institute on Alcohol Abuse and Alcoholism through cooperative agreements with the Harvard University School of Public Health (HD052102) (Principal Investigator: George Seage, Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke, Co-Principal Investigator: Kenneth Rich, Project Director: Patrick Davis). Data management services were provided by the Frontier Science and Technology Research Foundation (Principal Investigator: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc. (Principal Investigator: Julie Davidson). NR 25 TC 26 Z9 26 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2011 VL 76 IS 6 BP 386 EP 391 DI 10.1159/000332957 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 866KA UT WOS:000298378300003 PM 22042056 ER PT J AU Zeger, MPD Shah, K Kowal, K Cutler, GB Kushner, H Ross, JL AF Zeger, Martha P. D. Shah, Kavita Kowal, Karen Cutler, Gordon B., Jr. Kushner, Harvey Ross, Judith L. TI Prospective Study Confirms Oxandrolone-Associated Improvement in Height in Growth Hormone-Treated Adolescent Girls with Turner Syndrome SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Article DE 45,X; Androgen; Stature; Estrogen; Bone age ID FINAL HEIGHT; THERAPY; WOMEN; ESTROGEN; COMBINATION; PROMOTION; FRACTURES; DENSITY; AGE AB Background/Aims: Untreated girls with Turner syndrome (TS) have growth failure, and adult height is, on average, 20 cm less than predicted height. Treatment with growth hormone (GH) is now standard of care. The objective of this study was to investigate the benefit of adding oxandrolone (Ox) to GH in a long-term, randomized, placebo (Pl)-controlled prospective trial to near adult height in TS. Methods: Prospective, randomized, Pl-controlled study: 76 girls with TS (ages 10-14.9 years) were randomized to receive Ox (0.06 mg/kg/day) or Pl in combination with GH (0.35 mg/kg/week, daily) over 2 years. Auxologic data, breast and pubic hair Tanner stages, and hormone and lipid levels were measured. Subjects who chose to continue were followed in a 2-year double-blind extension, also received estrogen therapy (years 3, 4), and had dual-energy X-ray absorptiometry evaluation of bone density (years 3, 4). Results: At year 4, the change in absolute height and height SDS was greater in the GH/Ox versus GH/Pl group [26.2 +/- 6.7 vs. 22.2 +/- 5.1 cm, analysis of covariance (ANCOVA) p < 0.001; 1.8 +/- 0.9 vs. 1.2 +/- 0.7 standard deviation scores, ANCOVA p < 0.001]. Bone mineral density (BMD) of the wrist (0.51 +/- 0.17 vs. 0.54 +/- 0.05 g/cm(2)) and spine (0.91 +/- 0.34 vs. 0.96 +/- 0.13 g/cm(2)) in the GH/Ox versus GH/Pl groups was similar after 4 years. Breast development was slower in the GH/Ox versus GH/Pl group [year 4: Tanner stage 2.9 +/- 1.3 (Ox) vs. 4.1 +/- 1.3 (Pl), p = 0.003], and menarche was approximately 1 year later. Conclusions: The addition of Ox to GH at mean age 12.0 +/- 1.7 year augmented height gain after 4 years of treatment, slowed breast development and did not affect BMD in girls with TS. Whether initiation of Ox prior to initiation of pubertal development would optimize height gain without impeding breast development will require further study. Copyright (C) 2010 S. Karger AG, Basel C1 [Ross, Judith L.] Thomas Jefferson Univ, Div Endocrinol, Dept Pediat, Philadelphia, PA 19107 USA. [Zeger, Martha P. D.; Ross, Judith L.] duPont Hosp Children Nemours, Dept Pediat, Wilmington, DE USA. [Cutler, Gordon B., Jr.] NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. [Kushner, Harvey] Biomed Comp Res Inst, Philadelphia, PA USA. RP Ross, JL (reprint author), Thomas Jefferson Univ, Div Endocrinol, Dept Pediat, 1025 Walnut St,Suite 726, Philadelphia, PA 19107 USA. EM Judith.Ross@mail.tju.edu OI Arora, Kavita/0000-0002-9912-9466 FU Eli Lilly Company; Pfizer; Novo Nordisk FX M.Z., K. S., K. K., and H. K. have nothing to disclose. G. B. C is a former employee, retiree (with pension) and current consultant of Eli Lilly & Company. J.L.R. has received grant support from Eli Lilly & Company, Pfizer, and Novo Nordisk and has served as a consultant for Eli Lilly & Company, Pfizer, and Novo Nordisk. NR 28 TC 21 Z9 24 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2011 VL 75 IS 1 BP 38 EP 46 DI 10.1159/000317529 PG 9 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 709GU UT WOS:000286427200008 PM 20733274 ER PT J AU Aros, S Mills, JL Iniguez, G Avila, A Conley, MR Troendle, J Cox, C Cassorla, F AF Aros, Sofia Mills, James L. Iniguez, German Avila, Alejandra Conley, Mary R. Troendle, James Cox, Christopher Cassorla, Fernando TI Effects of Prenatal Ethanol Exposure on Postnatal Growth and the Insulin-Like Growth Factor Axis SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Article DE Fetal alcohol syndrome; Pregnancy; Alcohol abuse; Insulin-like growth factor I; Insulin-like growth factor II ID FETAL ALCOHOL SYNDROME; FOR-GESTATIONAL-AGE; FACTOR-I; IGF-I; BINDING-PROTEINS; OFFSPRING SIZE; LEPTIN LEVELS; CHILDREN; WEIGHT; BIRTH AB Aims:To study the effect of in-utero alcohol exposure on the insulin-like growth factor axis (IGF) and leptin during infancy and childhood, considering that exposed children may exhibit pre- and postnatal growth retardation. Methods: We prospectively identified heavily drinking pregnant women who consumed on average 4 or more drinks of ethanol per day (>= 48 g/day) and assessed growth in 69 of their offspring and an unexposed control group of 83 children, measuring serum IGF-I (radioimmunoassay), IGF-II (immunoradiometric assay, IRMA), insulin-like growth factor-binding protein 3 (IGFBP-3) (IRMA) and leptin (IRMA) at 1 month and 1, 2, 3, 4, and 5 years of age. Results: IGF-II levels increased with age in both groups, but the rate of increase was significantly higher in exposed children, and levels were significantly higher in ethanol-exposed children at 3, 4, and 5 years of age. In exposed children, IGF-I levels were higher at 3 and 4 years and leptin levels were significantly lower at 1 and 2 years. Exposed subjects showed a much lower correlation between IGF-I and growth parameters than unexposed subjects. Conclusion: Exposure to ethanol during pregnancy increases IGF-I and IGF-II and decreases leptin during early childhood. The increase in serum IGF-II concentrations in ethanol-exposed children suggests that this hormone should be explored as a potential marker for prenatal alcohol exposure. Copyright (C) 2010 S. Karger AG, Basel C1 [Aros, Sofia] Univ Chile, Fac Med, Dept Pediat, San Borja Arriaran Clin Hosp, Santiago 7, Chile. [Iniguez, German; Avila, Alejandra; Cassorla, Fernando] Univ Chile, Fac Med, Inst Maternal & Child Res, Santiago 7, Chile. [Mills, James L.; Conley, Mary R.; Troendle, James; Cox, Christopher] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Mills, JL (reprint author), NICHD, NIH, DHHS, 6100 Bldg,Room 7 B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, USA FX This study was funded by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA. NR 42 TC 11 Z9 12 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2011 VL 75 IS 3 BP 166 EP 173 DI 10.1159/000319706 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 737LH UT WOS:000288569800002 PM 20847545 ER PT B AU Pequegnat, W AF Pequegnat, Willo BE Pequegnat, W Stover, E Boyce, CA TI Grantsmanship: Necessary but Not Sufficient Strategies for Success SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 NIMH, Int AIDS Prevent Res, Div AIDS, Rockville, MD 20857 USA. RP Pequegnat, W (reprint author), NIMH, Int AIDS Prevent Res, Div AIDS, Rockville, MD 20857 USA. EM WPequegn@mail.nih.gov; WPequegn@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 1 EP 7 DI 10.1007/978-1-4419-1454-5_1 D2 10.1007/978-1-4419-1454-5 PG 7 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000001 ER PT B AU Noronha, J AF Noronha, Jean BE Pequegnat, W Stover, E Boyce, CA TI Funding Opportunity Announcements SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 NIMH, Div Extramural Activ, Rockville, MD 20857 USA. RP Noronha, J (reprint author), NIMH, Div Extramural Activ, Rockville, MD 20857 USA. EM jnoronha@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 21 EP 28 DI 10.1007/978-1-4419-1454-5_3 D2 10.1007/978-1-4419-1454-5 PG 8 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000003 ER PT B AU Boyce, CA Aklin, CF AF Boyce, Cheryl Anne Aklin, Courtney Ferrell BE Pequegnat, W Stover, E Boyce, CA TI Selecting the Appropriate Research Mechanism: Finding the Right Match SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 [Boyce, Cheryl Anne] Natl Inst Drug Abuse, DCNBR, NIH, Rockville, MD USA. RP Boyce, CA (reprint author), Natl Inst Drug Abuse, DCNBR, NIH, Rockville, MD USA. EM cboyce@mail.nih.gov; cboyce@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 29 EP 47 DI 10.1007/978-1-4419-1454-5_4 D2 10.1007/978-1-4419-1454-5 PG 19 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000004 ER PT B AU Noronha, J AF Noronha, Jean BE Pequegnat, W Stover, E Boyce, CA TI Electronic Submission Process SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 NIMH, Div Extramural Activ, Bethesda, MD 20892 USA. RP Noronha, J (reprint author), NIMH, Div Extramural Activ, Bethesda, MD 20892 USA. EM jnoronha@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 59 EP 79 DI 10.1007/978-1-4419-1454-5_6 D2 10.1007/978-1-4419-1454-5 PG 21 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000006 ER PT B AU Folkman, S Pequegnat, W AF Folkman, Susan Pequegnat, Willo BE Pequegnat, W Stover, E Boyce, CA TI Common Mistakes in Proposal Writing and How to Avoid Them SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 [Pequegnat, Willo] NIMH, Div AIDS, Bethesda, MD USA. RP Folkman, S (reprint author), 117 Roblar Ave, Hillsborough, CA 94010 USA. EM susan.folkman@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 95 EP 103 DI 10.1007/978-1-4419-1454-5_8 D2 10.1007/978-1-4419-1454-5 PG 9 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000008 ER PT B AU Stover, E AF Stover, Ellen BE Pequegnat, W Stover, E Boyce, CA TI The Award Process SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 NIMH, Div AIDS Res, Bethesda, MD 20892 USA. RP Stover, E (reprint author), NIMH, Div AIDS Res, Bethesda, MD 20892 USA. EM estover@mail.nih.gov; estover@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 115 EP 122 DI 10.1007/978-1-4419-1454-5_10 D2 10.1007/978-1-4419-1454-5 PG 8 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000010 ER PT B AU Bentley, ME Tolley, EE Pequegnat, W AF Bentley, Margaret E. Tolley, Elizabeth E. Pequegnat, Willo BE Pequegnat, W Stover, E Boyce, CA TI Qualitative Inquiry: An End Not Just a Means SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter ID MARITAL HIV RISK; POLITICAL-ECONOMY; HEALTH-EDUCATION; INFIDELITY; MARRIAGE; WOMEN C1 [Bentley, Margaret E.] UNC Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. [Pequegnat, Willo] NIMH, Div AIDS, Bethesda, MD USA. RP Bentley, ME (reprint author), UNC Gillings Sch Global Publ Hlth, Dept Nutr, 124 Rosenau Hall,CB 7400, Chapel Hill, NC 27599 USA. EM pbentley@unc.edu NR 48 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 153 EP 172 DI 10.1007/978-1-4419-1454-5_14 D2 10.1007/978-1-4419-1454-5 PG 20 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000014 ER PT B AU Wishnoff, CM Hayes-Shell, P Shore, D Boyce, CA AF Wishnoff, Christine Moretto Hayes-Shell, Pamela Shore, David Boyce, Cheryl Anne BE Pequegnat, W Stover, E Boyce, CA TI Human Subject Protection and Special Population Issues SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 [Wishnoff, Christine Moretto] NIMH, Off Associate Director Clin Res, Bethesda, MD 20892 USA. [Hayes-Shell, Pamela] Chestnut Lodge Hosp, Patient Care Serv, Rockville, MD USA. [Shore, David] NIH, Intramural CNS IRB, Bethesda, MD 20892 USA. [Boyce, Cheryl Anne] Natl Inst Drug Abuse, DCNBR, NIH, DHHS, Bethesda, MD USA. [Boyce, Cheryl Anne] NIMH, NIH, DHHS, Bethesda, MD 20892 USA. RP Wishnoff, CM (reprint author), NIMH, Off Associate Director Clin Res, Bethesda, MD 20892 USA. EM morettoc2@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 247 EP 266 DI 10.1007/978-1-4419-1454-5_19 D2 10.1007/978-1-4419-1454-5 PG 20 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000019 ER PT B AU Quinn, K Nakamura, R AF Quinn, Kevin Nakamura, Richard BE Pequegnat, W Stover, E Boyce, CA TI Animal Welfare and Behavior SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 [Quinn, Kevin] NIMH, Behav Sci & Integrat Neurosci Res Branch, Bethesda, MD USA. [Nakamura, Richard] NIMH, Neuropsychol Lab, Bethesda, MD USA. [Nakamura, Richard] NIMH, Psychol Lab, Bethesda, MD USA. RP Quinn, K (reprint author), NIMH, Behav Sci & Integrat Neurosci Res Branch, Bethesda, MD USA. EM kquinn@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 267 EP 275 DI 10.1007/978-1-4419-1454-5_20 D2 10.1007/978-1-4419-1454-5 PG 9 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000020 ER PT B AU Kytle, R Boyce, CA AF Kytle, Rayford Boyce, Cheryl Anne BE Pequegnat, W Stover, E Boyce, CA TI Developing a Resume and Presenting Your Research Team SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 [Kytle, Rayford] NIH, Div AIDS Res, Bethesda, MD 20892 USA. [Boyce, Cheryl Anne] Natl Inst Drug Abuse, DCNBR, NIH, DHHS, Bethesda, MD USA. [Boyce, Cheryl Anne] NIMH, NIH, DHHS, Bethesda, MD USA. RP Kytle, R (reprint author), NIH, Div AIDS Res, Bldg 10, Bethesda, MD 20892 USA. EM rkytle@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 277 EP 281 DI 10.1007/978-1-4419-1454-5_21 D2 10.1007/978-1-4419-1454-5 PG 5 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000021 ER PT B AU Strader, LC Pequegnat, W AF Strader, Lisa C. Pequegnat, Willo BE Pequegnat, W Stover, E Boyce, CA TI Developing a Quality Control/Quality Assurance Program SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 [Strader, Lisa C.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Pequegnat, Willo] NIMH, Div AIDS, Bethesda, MD 20892 USA. RP Strader, LC (reprint author), RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. EM lcs@rti.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 309 EP 330 DI 10.1007/978-1-4419-1454-5_24 D2 10.1007/978-1-4419-1454-5 PG 22 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000024 ER PT B AU Mayo, D AF Mayo, Donna BE Pequegnat, W Stover, E Boyce, CA TI Applying for Training, Career Development, and Early-stage Research Grants SO HOW TO WRITE A SUCCESSFUL RESEARCH GRANT APPLICATION: A GUIDE FOR SOCIAL AND BEHAVIORAL SCIENTISTS, SECOND EDITION LA English DT Article; Book Chapter C1 NIMH, Bethezda, MD USA. RP Mayo, D (reprint author), NIMH, Bethezda, MD USA. EM Mayo.Donna@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1453-8 PY 2011 BP 331 EP 337 DI 10.1007/978-1-4419-1454-5_25 D2 10.1007/978-1-4419-1454-5 PG 7 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA BRQ12 UT WOS:000283396000025 ER PT J AU Adriaansen, J Perez, P Zheng, C Collins, MT Baum, BJ AF Adriaansen, J. Perez, P. Zheng, C. Collins, M. T. Baum, B. J. TI Human Parathyroid Hormone Is Secreted Primarily into the Bloodstream After Rat Parotid Gland Gene Transfer SO HUMAN GENE THERAPY LA English DT Article ID DYNAMIC CELLULAR PROCESSES; MILK-ALKALI SYNDROME; SALIVARY-GLANDS; IN-VIVO; TRANSGENE EXPRESSION; SUBMANDIBULAR-GLANDS; ENDOCRINE SECRETION; ADENOVIRAL VECTOR; PROTEIN-SYNTHESIS; MEDIATED TRANSFER AB Hypoparathyroidism is a hormone deficiency syndrome that leads to low blood calcium levels and for which current replacement therapy is inadequate. Gene transfer to salivary glands leads to safe and abundant secretion of therapeutic protein into either saliva or the bloodstream. We previously reported the successful transduction of rat submandibular glands with an adenoviral vector encoding human parathyroid hormone (Ad.hPTH), but unfortunately most of the hPTH was secreted into saliva. Because submandibular and parotid glands are morphologically and functionally different, we hypothesized that hPTH sorting might be different in parotid glands. After 2 days, the pattern of hPTH secretion from transduced parotid glands of intact rats was reversed from that of transduced submandibular glands, that is, most transgenic hPTH was detected in serum (5x10(10) viral particles per gland; the saliva-to-serum ratio of total hPTH secreted was 0.04). Vector copies were localized to the targeted parotid glands, with none detected in liver or spleen. Ad.hPTH next was administered to parotid glands of parathyroidectomized rats. Two days after delivery no hPTH was detectable in saliva, but high levels were found in serum, leading to normalization of serum calcium and a significant increase in the urinary phosphorus-to-creatinine ratio. This study demonstrates for the first time differential sorting of transgenic hPTH between submandibular and parotid glands, suggesting that hPTH may be a valuable model protein for understanding the molecular basis of transgenic secretory protein sorting in these exocrine glands. We also show the clinical potential of salivary gland hPTH gene therapy for patients with hypoparathyroidism. C1 [Adriaansen, J.; Perez, P.; Zheng, C.; Baum, B. J.] Natl Inst Dent & Craniofacial Res, Gene Transfer Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Collins, M. T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Transfer Sect, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1N113, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Division of Intramural Research of the National Institute of Dental and Craniofacial Research FX The Division of Intramural Research of the National Institute of Dental and Craniofacial Research supported this research. The authors thank Dr. John Fox for valuable comments on an earlier version of this manuscript. NR 55 TC 8 Z9 9 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2011 VL 22 IS 1 BP 84 EP 92 DI 10.1089/hum.2010.097 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 709PT UT WOS:000286453600011 PM 20977345 ER PT J AU Feldman, SA Goff, SL Xu, H Black, MA Kochenderfer, JN Johnson, LA Yang, JC Wang, QO Parkhurst, MR Cross, S Morgan, RA Cornetta, K Rosenberg, SA AF Feldman, Steven A. Goff, Stephanie L. Xu, Hui Black, Mary A. Kochenderfer, James N. Johnson, Laura A. Yang, James C. Wang, Qiong Parkhurst, Maria R. Cross, Scott Morgan, Richard A. Cornetta, Kenneth Rosenberg, Steven A. TI Rapid Production of Clinical-Grade Gammaretroviral Vectors in Expanded Surface Roller Bottles Using a "Modified" Step-Filtration Process for Clearance of Packaging Cells SO HUMAN GENE THERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; SERUM-FREE MEDIA; RETROVIRAL VECTORS; CANCER REGRESSION; GENE-TRANSFER; HIGH-TITER; SUSPENSION; LINE; TCR; TRANSDUCTION AB Production of clinical-grade gammaretroviral vectors for ex vivo gene delivery requires a scalable process that can rapidly generate large amounts of vector supernatant, clear large numbers of residual packaging cells with minimal decreases in vector titer, and satisfy all current regulatory guidelines regarding product biosafety. To that end, we have developed a simplified method that is compliant with current good manufacturing practices for the production of clinical-grade gammaretroviral vectors in a clinical research environment. We validated a large-scale production platform utilizing 1,700-cm(2) expanded surface roller bottles and a "modified'' step-filtration process consisting of a 40/150-mu m dual-screen filter for aggregate removal followed by a Sepacell 500II leukocyte reduction filter for removal of residual packaging cells. This clarification process can clear at least 2x10(9) viable producer cells using a single filter set-up without any significant loss of titer post-filtration. This platform typically generates 18 liters of vector supernatant to support small-scale clinical trials, but can easily be scaled up to 70 liters during a single manufacturing run. To date, this platform has generated five clinical-grade gammaretroviral vector products, four of which are now being used in adoptive cell therapy clinical trials for the treatment of a variety of solid cancers. C1 [Feldman, Steven A.] Natl Canc Inst, Surg Branch, ACRF, NIH, Bethesda, MD 20892 USA. [Goff, Stephanie L.] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA. [Johnson, Laura A.] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. [Cross, Scott; Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Cornetta, Kenneth] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. [Cornetta, Kenneth] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Feldman, SA (reprint author), Natl Canc Inst, Surg Branch, ACRF, NIH, 10 Ctr Dr,MSC 1201,Bldg 10,1B37A, Bethesda, MD 20892 USA. EM feldmanst@mail.nih.gov RI Johnson, Laura/H-4861-2013 NR 24 TC 9 Z9 9 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2011 VL 22 IS 1 BP 107 EP 115 DI 10.1089/hum.2010.064 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 709PT UT WOS:000286453600014 PM 20662590 ER PT J AU Molinaro, AM Carriero, N Bjornson, R Hartge, P Rothman, N Chatterjee, N AF Molinaro, Annette M. Carriero, Nicholas Bjornson, Robert Hartge, Patricia Rothman, Nathaniel Chatterjee, Nilanjan TI Power of Data Mining Methods to Detect Genetic Associations and Interactions SO HUMAN HEREDITY LA English DT Article DE Genetic associations; Power; Random forests; SNP; Variable importance measure ID NON-HODGKIN-LYMPHOMA; VARIABLE IMPORTANCE MEASURES; RANDOM FOREST; CYTOKINE POLYMORPHISMS; RISK; PATHWAY; REGRESSION AB Background: Genetic association studies, thus far, have focused on the analysis of individual main effects of SNP markers. Nonetheless, there is a clear need for modeling epistasis or gene-gene interactions to better understand the biologic basis of existing associations. Tree-based methods have been widely studied as tools for building prediction models based on complex variable interactions. An understanding of the power of such methods for the discovery of genetic associations in the presence of complex interactions is of great importance. Here, we systematically evaluate the power of three leading algorithms: random forests (RF), Monte Carlo logic regression (MCLR), and multifactor dimensionality reduction (MDR). Methods: We use the algorithm-specific variable importance measures (VIMs) as statistics and employ permutation-based resampling to generate the null distribution and associated p values. The power of the three is assessed via simulation studies. Additionally, in a data analysis, we evaluate the associations between individual SNPs in pro-inflammatory and immunoregulatory genes and the risk of non-Hodgkin lymphoma. Results: The power of RF is highest in all simulation models, that of MCLR is similar to RF in half, and that of MDR is consistently the lowest. Conclusions: Our study indicates that the power of RF VIMs is most reliable. However, in addition to tuning parameters, the power of RF is notably influenced by the type of variable (continuous vs. categorical) and the chosen VIM. Copyright (C) 2011 S. Karger AG, Basel C1 [Molinaro, Annette M.] Yale Univ, Div Biostat, Sch Publ Hlth, New Haven, CT 06519 USA. [Carriero, Nicholas; Bjornson, Robert] Yale Univ, Dept Comp Sci, New Haven, CT 06519 USA. [Hartge, Patricia; Rothman, Nathaniel; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Molinaro, AM (reprint author), Yale Univ, Div Biostat, Sch Publ Hlth, New Haven, CT 06519 USA. EM annette.molinaro@yale.edu FU National Institutes of Health (NIH) National Cancer Institute [K-22 CA123146]; National Center for Research Resources, a component of the NIH; NIH Roadmap for Medical Research [UL1 RR024139]; Yale University Biomedical High Performance Computing Center; NIH [RR19895] FX We would like to thank Zeynep Kalaylioglu, Bill Wheeler, and Charmila Fernandes. This work was supported by the National Institutes of Health (NIH) National Cancer Institute (K-22 CA123146 to A.M.M.), the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research (CTSA grant number UL1 RR024139 to A.M.M.), and the Yale University Biomedical High Performance Computing Center and NIH Grant (RR19895 for instrumentation). NR 34 TC 13 Z9 13 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 72 IS 2 BP 85 EP 97 DI 10.1159/000330579 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 842AO UT WOS:000296558000002 PM 21934324 ER PT J AU Ciampa, J Yeager, M Jacobs, K Thun, MJ Gapstur, S Albanes, D Virtamo, J Weinstein, SJ Giovannucci, E Willett, WC Cancel-Tassin, G Cussenot, O Valeri, A Hunter, D Hoover, R Thomas, G Chanock, S Holmes, C Chatterjee, N AF Ciampa, Julia Yeager, Meredith Jacobs, Kevin Thun, Michael J. Gapstur, Susan Albanes, Demetrius Virtamo, Jarmo Weinstein, Stephanie J. Giovannucci, Edward Willett, Walter C. Cancel-Tassin, Geraldine Cussenot, Olivier Valeri, Antoine Hunter, David Hoover, Robert Thomas, Gilles Chanock, Stephen Holmes, Chris Chatterjee, Nilanjan TI Application of a Novel Score Test for Genetic Association Incorporating Gene-Gene Interaction Suggests Functionality for Prostate Cancer Susceptibility Regions SO HUMAN HEREDITY LA English DT Article DE Gene-gene interaction; Score test; Prostate cancer ID GENOME-WIDE ASSOCIATION; HEPARAN-SULFATE ENDOSULFATASE; ENVIRONMENT INTERACTION; MULTIPLE LOCI; SIGNALING PATHWAY; VITAMIN-D; GROWTH; RECEPTOR; RISK; INDEPENDENCE AB Aims: We introduce an innovative multilocus test for disease association. It is an extension of an existing score test that gains power over alternative methods by incorporating a parsimonious one-degree-of-freedom model for interaction. We use our method in applications designed to detect interactions that generate hypotheses about the functionality of prostate cancer (PRCA) susceptibility regions. Methods: Our proposed score test is designed to gain additional power through the use of a retrospective likelihood that exploits an assumption of independence between unlinked loci in the underlying population. Its performance is validated through simulation. The method is used in conditional scans with data from stage II of the Cancer Genetic Markers of Susceptibility PRCA genome-wide association study. Results: Our proposed method increases power to detect susceptibility loci in diverse settings. It identified two high-ranking, biologically interesting interactions: (1) rs748120 of NR2C2 and subregions of 8q24 that contain independent susceptibility loci specific to PRCA and (2) rs4810671 of SULF2 and both JAZF1 and HNF1B that are associated with PRCA and type 2 diabetes. Conclusions: Our score test is a promising multilocus tool for genetic epidemiology. The results of our applications suggest functionality for poorly understood PRCA susceptibility regions. They motivate replication study. Copyright (C) 2011 S. Karger AG, Basel C1 [Ciampa, Julia; Albanes, Demetrius; Weinstein, Stephanie J.; Hoover, Robert; Chatterjee, Nilanjan] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Ciampa, Julia; Holmes, Chris] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Yeager, Meredith; Jacobs, Kevin; Hunter, David] NCI, Core Genotype Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Thun, Michael J.; Gapstur, Susan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Giovannucci, Edward; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] CeRePP Hop Tenon, Assistance Publ Hop Paris, Paris, France. [Thomas, Gilles] Ctr Leon Berard, INSERM, U590, F-69373 Lyon, France. [Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Frederick, MD 21701 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, EPS 8038,6120 Execut Blvd, Rockville, MD 20852 USA. EM chattern@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU Medical Research Council [MC_UP_A390_1107]; Wellcome Trust [090532] NR 65 TC 4 Z9 4 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 72 IS 3 BP 182 EP 193 DI 10.1159/000331222 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 857TD UT WOS:000297741800004 PM 22086326 ER PT J AU Bailey-Wilson, JE Wilson, AF AF Bailey-Wilson, Joan E. Wilson, Alexander F. TI Linkage Analysis in the Next-Generation Sequencing Era SO HUMAN HEREDITY LA English DT Article DE Linkage; Genetics; DNA sequence; Whole-genome sequence; Whole-exome sequence ID BETA-HYDROXYLASE ACTIVITY; DISEASE SUSCEPTIBILITY LOCI; REGRESSIVE LOGISTIC-MODELS; HETEROGENEITY LOD SCORES; POLYMORPHIC DNA MARKER; I ERROR PROBABILITIES; SIB-PAIR TESTS; GENETIC-LINKAGE; SEGREGATION ANALYSIS; CROHNS-DISEASE AB Linkage analysis was developed to detect excess co-segregation of the putative alleles underlying a phenotype with the alleles at a marker locus in family data. Many different variations of this analysis and corresponding study design have been developed to detect this co-segregation. Linkage studies have been shown to have high power to detect loci that have alleles (or variants) with a large effect size, i.e. alleles that make large contributions to the risk of a disease or to the variation of a quantitative trait. However, alleles with a large effect size tend to be rare in the population. In contrast, association studies are designed to have high power to detect common alleles which tend to have a small effect size for most diseases or traits. Although genome-wide association studies have been successful in detecting many new loci with common alleles of small effect for many complex traits, these common variants often do not explain a large proportion of disease risk or variation of the trait. In the past, linkage studies were successful in detecting regions of the genome that were likely to harbor rare variants with large effect for many simple Mendelian diseases and for many complex traits. However, identifying the actual sequence variant(s) responsible for these linkage signals was challenging because of difficulties in sequencing the large regions implicated by each linkage peak. Current 'next-generation' DNA sequencing techniques have made it economically feasible to sequence all exons or the whole genomes of a reasonably large number of individuals. Studies have shown that rare variants are quite common in the general population, and it is now possible to combine these new DNA sequencing methods with linkage studies to identify rare causal variants with a large effect size. A brief review of linkage methods is presented here with examples of their relevance and usefulness for the interpretation of whole-exome and whole-genome sequence data. Copyright (C) 2011 S. Karger AG, Basel C1 [Bailey-Wilson, Joan E.; Wilson, Alexander F.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. RP Bailey-Wilson, JE (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM jebw@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920 NR 155 TC 43 Z9 45 U1 1 U2 16 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 72 IS 4 BP 228 EP 236 DI 10.1159/000334381 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 876CU UT WOS:000299085600002 PM 22189465 ER PT J AU Schaffer, AA Lemire, M Ott, J Lathrop, GM Weeks, DE AF Schaeffer, Alejandro A. Lemire, Mathieu Ott, Jurg Lathrop, G. Mark Weeks, Daniel E. TI Coordinated Conditional Simulation with SLINK and SUP of Many Markers Linked or Associated to a Trait in Large Pedigrees SO HUMAN HEREDITY LA English DT Article DE Coordinated conditional simulation; SLINK; SUP; Linkage study; Association study; Pedigree, large; Pedigree, complex ID LINKAGE ANALYSIS; COMPUTER-SIMULATION; POWER; GENE; MISCLASSIFICATION; EXTENSION; PROGRAM; DISEASE; MODEL AB Simulation of genotypes in pedigrees is an important tool to evaluate the power of a linkage or an association study and to assess the empirical significance of results. SLINK is a widely-used package for pedigree simulations, but its implementation has not previously been described in a published paper. SLINK was initially derived from the LINKAGE programs. Over the 20 years since its release, SLINK has been modified to incorporate faster algorithms, notably from the linkage analysis package FASTLINK, also derived from LINKAGE. While SLINK can simulate genotypes on pedigrees of high complexity, one limitation of SLINK, as with most methods based on peeling algorithms to evaluate pedigree likelihoods, is the small number of linked markers that can be generated. The software package SUP includes an elegant wrapper for SLINK that circumvents the limitation on number of markers by using descent markers generated by SLINK to simulate a much larger number of markers on the same chromosome, linked and possibly associated with a trait locus. We have released new coordinated versions of SLINK (3.0; available from http://watson.hgen.pitt.edu) and SUP (v090804; available from http://mlemire.freeshell.org/software or http://watson.hgen.pitt.edu) that integrate the two software packages. Thereby, we have removed some of the previous limitations on the joint functionality of the programs, such as the number of founders in a pedigree. We review the history of SLINK and describe how SLINK and SUP are now coordinated to permit the simulation of large numbers of markers linked and possibly associated with a trait in large pedigrees. Copyright (C) 2011 S. Karger AG, Basel C1 [Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20894 USA. [Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada. [Ott, Jurg] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Ott, Jurg] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. [Lathrop, G. Mark] CEA, Inst Genom, Ctr Natl Genotypage, Evry, France. [Lathrop, G. Mark] Fdn Jean Dausset CEPH, Paris, France. [Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, DHHS, Bldg 38A,Room 6S605,8600 Rockville Pike, Bethesda, MD 20894 USA. EM schaffer@helix.nih.gov RI Weeks, Daniel/B-2995-2012; Schaffer, Alejandro/F-2902-2012; OI Weeks, Daniel/0000-0001-9410-7228 FU University of Pittsburgh; National Institutes of Health, NLM FX This research was supported in part by the University of Pittsburgh and the Intramural Research Program of the National Institutes of Health, NLM. NR 24 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 71 IS 2 BP 126 EP 134 DI 10.1159/000324177 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 789FM UT WOS:000292500000006 PM 21734403 ER PT J AU Hiekkalinna, T Schaffer, AA Lambert, B Norrgrann, P Goring, HHH Terwilliger, JD AF Hiekkalinna, Tero Schaeffer, Alejandro A. Lambert, Brian Norrgrann, Petri Goering, Harald H. H. Terwilliger, Joseph D. TI PSEUDOMARKER: A Powerful Program for Joint Linkage and/or Linkage Disequilibrium Analysis on Mixtures of Singletons and Related Individuals SO HUMAN HEREDITY LA English DT Article DE Computer software; Family-based association; Genome-wide association; Likelihood methods; Linkage analysis; Linkage disequilibrium; Study design ID QUANTITATIVE-TRAIT LOCI; GENETIC-LINKAGE; RECOMBINATION FRACTIONS; NUCLEAR FAMILIES; UNIFIED APPROACH; 21ST CENTURIES; ASSOCIATION; LIKELIHOOD; POPULATION; PEDIGREES AB A decade ago, there was widespread enthusiasm for the prospects of genome-wide association studies to identify common variants related to common chronic diseases using samples of unrelated individuals from populations. Although technological advancements allow us to query more than a million SNPs across the genome at low cost, a disappointingly small fraction of the genetic portion of common disease etiology has been uncovered. This has led to the hypothesis that less frequent variants might be involved, stimulating a renaissance of the traditional approach of seeking genes using multiplex families from less diverse populations. However, by using the modern genotyping and sequencing technology, we can now look not just at linkage, but jointly at linkage and linkage disequilibrium (LD) in such samples. Software methods that can look simultaneously at linkage and LD in a powerful and robust manner have been lacking. Most algorithms cannot jointly analyze datasets involving families of varying structures in a statistically or computationally efficient manner. We have implemented previously proposed statistical algorithms in a user-friendly software package, PSEUDOMARKER. This paper is an announcement of this software package. We describe the motivation behind the approach, the statistical methods, and software, and we briefly demonstrate PSEUDOMARKER's advantages over other packages by example. Copyright (C) 2011 S. Karger AG, Basel C1 [Hiekkalinna, Tero; Norrgrann, Petri; Terwilliger, Joseph D.] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Hiekkalinna, Tero; Norrgrann, Petri] Natl Inst Hlth & Welf, Unit Publ Hlth Genom, Helsinki, Finland. [Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA. [Lambert, Brian] Penn State Univ, Dept Anthropol, State Coll, PA USA. [Goering, Harald H. H.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Terwilliger, Joseph D.] Columbia Univ, Dept Psychiat, New York, NY USA. [Terwilliger, Joseph D.] Columbia Univ, Dept Genet & Dev, New York, NY USA. [Terwilliger, Joseph D.] Columbia Univ, Columbia Genome Ctr, New York, NY USA. [Terwilliger, Joseph D.] New York State Psychiat Inst & Hosp, Div Med Genet, New York, NY 10032 USA. RP Hiekkalinna, T (reprint author), Biomedicum Helsinki, Natl Inst Hlth & Welf THL, Publ Hlth Genom Unit, POB 104, FI-00251 Helsinki, Finland. EM tero.hiekkalinna@helsinki.fi RI Schaffer, Alejandro/F-2902-2012 FU Academy of Finland; National Institutes of Health [MH84995, MH63749, MH059490, RR017515]; Helsingin Sanomat Centennial Foundation; Biomedicum Helsinki Foundation; Emil Aaltonen Foundation; Otto A. Malm Foundation; Jenny and Antti Wihuri Foundation; Finnish Cultural Society; NIH, NLM; CSC FX PSEUDOMARKER has been developed in collaboration with researchers of The Institute for Molecular Medicine Finland (FIMM) and Public Health Genomics Unit, National Institute for Health and Welfare (THL), as well as users from different institutions around the world, who have contributed valuable feedback. Funding from the FiDiPro program of the Academy of Finland, grants MH84995, MH63749, MH059490, and RR017515 from the National Institutes of Health, the Helsingin Sanomat Centennial Foundation, Biomedicum Helsinki Foundation, Emil Aaltonen Foundation, Otto A. Malm Foundation, Jenny and Antti Wihuri Foundation and Finnish Cultural Society are gratefully acknowledged. This research was also supported by the Intramural Research Program of the NIH, NLM (A.A.S.). In 1993-1995, the co-localization of John Dennis, Doug Moore, and A.A.S. at the Computer Science Department of Rice University led to the first implementation of direct search into a version of ILINK. Maija Wessman, Verneri Anttila, Mari Kaunisto, and Tiina Paunio are acknowledged for providing Finnish migraine and schizophrenia pedigree structures for simulation studies. Markus Perola and Leena Peltonen-Palotie are thanked for their guidance and support over the years. Finnish IT Center for Science (CSC) Linux-based supercomputers Murska and Vuori were used for doing massive computer simulations, and support from CSC is greatly acknowledged. NR 53 TC 17 Z9 18 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2011 VL 71 IS 4 BP 256 EP 266 DI 10.1159/000329467 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 806UI UT WOS:000293838400005 PM 21811076 ER PT J AU Bakker, GR Uribe, MR Adams, SD Flegel, WA AF Bakker, Gina R. Uribe, Marcela R. Adams, Sharon D. Flegel, Willy A. TI ALLELE FREQUENCY ASSESSMENT OF 18 MINOR HISTOCOMPATIBILITY ANTIGENS (Mhags) IN AFRICAN AMERICANS SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2011 CL New Orleans, LA SP Amer Soc Histocompatibility & Immunogenet C1 [Bakker, Gina R.; Uribe, Marcela R.; Adams, Sharon D.; Flegel, Willy A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2011 VL 72 SU 1 BP S97 EP S97 PG 1 WC Immunology SC Immunology GA 833QY UT WOS:000295901200137 ER PT J AU Huvard, MJ Schmid, P Flegel, WA AF Huvard, Michael J. Schmid, Pirmin Flegel, Willy A. TI ALLELE FREQUENCIES OF HUMAN NEUTROPHIL ANTIGEN-3 (HNA-3) IN AN AFRICAN AMERICAN POPULATION SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-Society-for-Histocompatibility-and-Immunogenetics CY OCT 17-21, 2011 CL New Orleans, LA SP Amer Soc Histocompatibility & Immunogenet C1 [Huvard, Michael J.; Schmid, Pirmin; Flegel, Willy A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PY 2011 VL 72 SU 1 BP S123 EP S123 PG 1 WC Immunology SC Immunology GA 833QY UT WOS:000295901200184 ER PT J AU Thomas, KJ McCoy, MK Blackinton, J Beilina, A van der Brug, M Sandebring, A Miller, D Maric, D Cedazo-Minguez, A Cookson, MR AF Thomas, Kelly Jean McCoy, Melissa K. Blackinton, Jeff Beilina, Alexandra van der Brug, Marcel Sandebring, Anna Miller, David Maric, Dragan Cedazo-Minguez, Angel Cookson, Mark R. TI DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy SO HUMAN MOLECULAR GENETICS LA English DT Article ID PARKINSONISM PROTEIN DJ-1; OXIDATIVE STRESS; CELL-DEATH; RECESSIVE PARKINSONISM; ANTIOXIDATIVE STRESS; ALPHA-SYNUCLEIN; PINK1; DISEASE; KINASE; MICE AB Mutations in DJ-1, PINK1 (PTEN-induced putative kinase 1) and parkin all cause recessive parkinsonism in humans, but the relationships between these genes are not clearly defined. One event associated with loss of any of these genes is altered mitochondrial function. Recent evidence suggests that turnover of damaged mitochondria by autophagy might be central to the process of recessive parkinsonism. Here, we show that loss of DJ-1 leads to loss of mitochondrial polarization, fragmentation of mitochondria and accumulation of markers of autophagy (LC3 punctae and lipidation) around mitochondria in human dopaminergic cells. These effects are due to endogenous oxidative stress, as antioxidants will reverse all of them. Similar to PINK1 and parkin, DJ-1 also limits mitochondrial fragmentation in response to the mitochondrial toxin rotenone. Furthermore, overexpressed parkin will protect against loss of DJ-1 and, although DJ-1 does not alter PINK1 mitochondrial phenotypes, DJ-1 is still active against rotenone-induced damage in the absence of PINK1. None of the three proteins complex together using size exclusion chromatography. These data suggest that DJ-1 works in parallel to the PINK1/parkin pathway to maintain mitochondrial function in the presence of an oxidative environment. C1 [Thomas, Kelly Jean; McCoy, Melissa K.; Blackinton, Jeff; Beilina, Alexandra; van der Brug, Marcel; Sandebring, Anna; Miller, David; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Sandebring, Anna; Cedazo-Minguez, Angel] Karolinska Inst, Dept NVS, KI Alzheimers Dis Res Ctr, Novum, Stockholm, Sweden. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov RI Cedazo-Minguez, Angel/C-6707-2012 OI Cedazo-Minguez, Angel/0000-0003-4626-4864 FU National Institute on Aging, National Institutes of Health [Z01-AG000953]; Parkinsonfonden; Stohnes foundation; Gamla Tjanarinnor Foundation; NHR foundation; Riksbanken Jubileumfonden, Sweden; K&A Wallenberg Foundation; Swedish Brain Power Initiative FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (Project Z01-AG000953). This study was also supported by grants from the Parkinsonfonden, Stohnes foundation, Gamla Tjanarinnor Foundation, NHR foundation and Riksbanken Jubileumfonden, Sweden, The K&A Wallenberg Foundation and the Swedish Brain Power Initiative. NR 58 TC 170 Z9 183 U1 0 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN PY 2011 VL 20 IS 1 BP 40 EP 50 DI 10.1093/hmg/ddq430 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 692ZE UT WOS:000285193600004 PM 20940149 ER PT J AU Almeida, MQ Tsang, KM Cheadle, C Watkins, T Grivel, JC Nesterova, M Goldbach-Mansky, R Stratakis, CA AF Almeida, Madson Q. Tsang, Kit Man Cheadle, Chris Watkins, Tonya Grivel, Jean-Charles Nesterova, Maria Goldbach-Mansky, Raphaela Stratakis, Constantine A. TI Protein kinase A regulates caspase-1 via Ets-1 in bone stromal cell-derived lesions: a link between cyclic AMP and pro-inflammatory pathways in osteoblast progenitors SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSCRIPTION FACTORS; GENETIC-HETEROGENEITY; C-ETS-1 PROTOONCOGENE; BINDING-PROTEIN; CARNEY COMPLEX; ALPHA-SUBUNIT; EXPRESSION; DISEASE; DIFFERENTIATION; MUTATION AB Patients with genetic defects of the cyclic (c) adenosine-monophosphate (AMP)-signaling pathway and those with neonatal-onset multisystem inflammatory disease (NOMID) develop tumor-like lesions of the long bones. The molecular basis of this similarity is unknown. NOMID is caused by inappropriate caspase-1 activity, which in turn activates the inflammasome. The present study demonstrates that NOMID bone lesions are derived from the same osteoblast progenitor cells that form fibroblastoid tumors in mice and humans with defects that lead to increased cAMP-dependent protein kinase A (PKA) signaling. NOMID tumor cells showed high PKA activity, and an increase in their cAMP signaling led to PKA-specific activation of caspase- 1. Increased PKA led to inflammation-independent activation of caspase-1 via over-expression of the proto-oncogene (and early osteoblast factor) Ets-1. In NOMID tumor cells, as in cells with defective PKA regulation, increased prostaglandin E2 (PGE2) led to increased cAMP levels and activation of Wnt signaling, like in other states of inappropriate PKA activity. Caspase-1 and PGE2 inhibition led to a decrease in cell proliferation of both NOMID and cells with abnormal PKA. These data reveal a previously unsuspected link between abnormal cAMP signaling and defective regulation of the inflammasome and suggest that caspase-1 and PGE2 inhibition may be therapeutic targets in bone lesions associated with defects of these two pathways. C1 [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,NIH Clin Res Ctr, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. [Grivel, Jean-Charles] NICHD, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Cheadle, Chris; Watkins, Tonya] Johns Hopkins Univ, Div Allergy & Clin Immunol, Sch Med, Baltimore, MD 21224 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,NIH Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3216,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU US National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development [Z01-HD-000642-04]; NIAMS FX This work was supported by US National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural project Z01-HD-000642-04 (to C. A. S.) and the NIAMS Intramural Research. Recent data (50) add support to PKA and/or involvement of Prkar1a in early osteoblast proliferation, and this pathway's significant involvement in human osteosarcoma. It would be interesting to study caspase-1 and/or the inflammasome in this human tumor. NR 50 TC 18 Z9 18 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JAN PY 2011 VL 20 IS 1 BP 165 EP 175 DI 10.1093/hmg/ddq455 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 692ZE UT WOS:000285193600014 PM 20940146 ER PT J AU Gremer, L Merbitz-Zahradnik, T Dvorsky, R Cirstea, IC Kratz, CP Zenker, M Wittinghofer, A Ahmadian, MR AF Gremer, Lothar Merbitz-Zahradnik, Torsten Dvorsky, Radovan Cirstea, Ion C. Kratz, Christian Peter Zenker, Martin Wittinghofer, Alfred Ahmadian, Mohammad Reza TI Germline KRAS Mutations Cause Aberrant Biochemical and Physical Properties Leading to Developmental Disorders SO HUMAN MUTATION LA English DT Article DE Noonan syndrome; NS; gain of function; GAP resistance; KRAS; Ras isoforms; Ras mutations ID ONCOGENIC RAS MUTANTS; GTPASE-ACTIVATING PROTEINS; SWITCH I-REGION; COSTELLO-SYNDROME; NUCLEOTIDE EXCHANGE; STRUCTURAL BASIS; SIGNAL-TRANSDUCTION; NOONAN-SYNDROME; CRYSTAL-STRUCTURE; BINDING PROTEINS AB The KRAS gene is the most common locus for somatic gain-of-function mutations in human cancer. Germline KRAS mutations were shown recently to be associated with developmental disorders, including Noonan syndrome (NS), cardio-facio-cutaneous syndrome (CFCS), and Costello syndrome (CS). The molecular basis of this broad phenotypic variability has in part remained elusive so far. Here, we comprehensively analyzed the biochemical and structural features of ten germline KRAS mutations using physical and cellular biochemistry. According to their distinct biochemical and structural alterations, the mutants can be grouped into five distinct classes, four of which markedly differ from RAS oncoproteins. Investigated functional alterations comprise the enhancement of intrinsic and guanine nucleotide exchange factor (GEF) catalyzed nucleotide exchange, which is alternatively accompanied by an impaired GTPase-activating protein (GAP) stimulated GTP hydrolysis, an overall loss of functional properties, and a deficiency in effector interaction. In conclusion, our data underscore the important role of RAS in the pathogenesis of the group of related disorders including NS, CFCS, and CS, and provide clues to the high phenotypic variability of patients with germline KRAS mutations. Hum Mutat 32:33-43, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Gremer, Lothar; Merbitz-Zahradnik, Torsten; Dvorsky, Radovan; Cirstea, Ion C.; Ahmadian, Mohammad Reza] Univ Dusseldorf, Inst Biochem & Mol Biol 2, Fac Med, D-40225 Dusseldorf, Germany. [Zenker, Martin] Univ Hosp Magdeburg, Inst Human Genet, Magdeburg, Germany. [Kratz, Christian Peter] NCI, Clin Genet Branch, DCEG, Rockville, MD USA. [Gremer, Lothar; Merbitz-Zahradnik, Torsten; Dvorsky, Radovan] Max Planck Inst Mol Physiol, Dept Biol Struct, D-44139 Dortmund, Germany. RP Ahmadian, MR (reprint author), Univ Dusseldorf, Inst Biochem & Mol Biol 2, Fac Med, Univ Str 1, D-40225 Dusseldorf, Germany. EM Reza.Ahmadian@uni-duesseldorf.de RI Gremer, Lothar/H-9128-2013 OI Gremer, Lothar/0000-0001-7065-5027 FU German Research Foundation [DFG AH 92/5-1]; German Ministry of Science and Education (BMBF) [01GS08100]; Research Committee of the Medical Faculty of the Heinrich-Heine University Dusseldorf; Max-Planck Society; E-Rare project NSEuroNet FX Grant sponsor: The German Research Foundation; Grant number: DFG AH 92/5-1; Grant sponsor: The NGFNplus program of the German Ministry of Science and Education (BMBF); Grant number: 01GS08100; Grant sponsors: The Research Committee of the Medical Faculty of the Heinrich-Heine University Dusseldorf; Max-Planck Society; E-Rare project NSEuroNet. NR 89 TC 35 Z9 38 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2011 VL 32 IS 1 BP 33 EP 43 DI 10.1002/humu.21377 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 707JH UT WOS:000286281800012 PM 20949621 ER PT J AU Farrance, CE Chichester, JA Musiychuk, K Shamloul, M Rhee, A Manceva, SD Jones, RM Mamedov, T Sharma, S Mett, V Streatfield, SJ Roeffen, W van de Vegte-Bolmer, M Sauerwein, RW Wu, YM Muratova, O Miller, L Duffy, P Sinden, R Yusibov, V AF Farrance, Christine E. Chichester, Jessica A. Musiychuk, Konstantin Shamloul, Moneim Rhee, Amy Manceva, Slobodanka D. Jones, R. Mark Mamedov, Tarlan Sharma, Satish Mett, Vadim Streatfield, Stephen J. Roeffen, Will van de Vegte-Bolmer, Marga Sauerwein, Robert W. Wu, Yimin Muratova, Olga Miller, Louis Duffy, Patrick Sinden, Robert Yusibov, Vidadi TI Antibodies to plant-produced Plasmodium falciparum sexual stage protein Pfs25 exhibit transmission blocking activity SO HUMAN VACCINES LA English DT Article; Proceedings Paper CT 7th World Congress on Vaccines, Immunisation and Immunotherapy (WCVII) CY MAY 26-28, 2010 CL Berlin, GERMANY SP Infections Control World Org (ICWO) DE TBV; malaria; plants; Nicotiana benthamiana; Pfs25; recombinant vaccine ID AERUGINOSA EXOPROTEIN-A; MALARIA VACCINE; PICHIA-PASTORIS; EXPRESSION; INFLUENZA; IMMUNOGENICITY; HEMAGGLUTININ; ERADICATION; STRATEGIES; CHALLENGE AB Malaria is a serious and sometimes fatal mosquito-borne disease caused by a protozoan parasite. Each year, it is estimated that over one million people are killed by malaria, yet the disease is preventable and treatable. Developing vaccines against the parasite is a critical component in the fight against malaria and these vaccines can target different stages of the pathogen's life cycle. We are targeting sexual stage proteins of P. falciparum which are found on the surface of the parasite reproductive cells present in the mosquito gut. Antibodies against these proteins block the progression of the parasite's life cycle in the mosquito, and thus block transmission to the next human host. Transmission blocking vaccines are essential to the malaria eradication program to ease the disease burden at the population level. We have successfully produced multiple versions of the Pfs25 antigen in a plant virus-based transient expression system and have evaluated these vaccine candidates in an animal model. The targets are expressed in plants at a high level, are soluble and most importantly, generate strong transmission blocking activity as determined by a standard membrane feeding assay. These data demonstrate the feasibility of expressing Plasmodium antigens in a plant-based system for the economic production of a transmission blocking vaccine against malaria. C1 [Farrance, Christine E.; Chichester, Jessica A.; Musiychuk, Konstantin; Shamloul, Moneim; Rhee, Amy; Manceva, Slobodanka D.; Jones, R. Mark; Mamedov, Tarlan; Sharma, Satish; Mett, Vadim; Streatfield, Stephen J.; Yusibov, Vidadi] Fraunhofer USA Ctr Mol Biotechnol, Newark, DE USA. [Roeffen, Will; van de Vegte-Bolmer, Marga; Sauerwein, Robert W.] Radboud Univ Nijmegen, Ctr Med, Nijmegen Ctr Mol Life Sci, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands. [Wu, Yimin; Muratova, Olga; Miller, Louis; Duffy, Patrick] NIAID, LMIV, NIH, Rockville, MD USA. [Sinden, Robert] Univ London Imperial Coll Sci Technol & Med, Div Cell & Mol Biol, London, England. RP Yusibov, V (reprint author), Fraunhofer USA Ctr Mol Biotechnol, Newark, DE USA. EM vyusibov@fraunhofer-cmb.org RI Sauerwein, Robert/C-8519-2013; Roeffen, W.F.G./L-4607-2015; Mammedov, Tarlan/J-3853-2013 NR 31 TC 30 Z9 30 U1 0 U2 8 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8600 J9 HUM VACCINES JI Hum. Vaccines PD JAN-FEB PY 2011 VL 7 SU 1 BP 191 EP 198 DI 10.4161/hv.7.0.14588 PG 8 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 742ZM UT WOS:000288984200026 PM 21266847 ER PT J AU Lee, CR Pretorius, M Schuck, RN Burch, LH Bartlett, J Williams, SM Zeldin, DC Brown, NJ AF Lee, Craig R. Pretorius, Mias Schuck, Robert N. Burch, Lauranell H. Bartlett, Jackie Williams, Scott M. Zeldin, Darryl C. Brown, Nancy J. TI Genetic Variation in Soluble Epoxide Hydrolase (EPHX2) Is Associated With Forearm Vasodilator Responses in Humans SO HYPERTENSION LA English DT Article DE Soluble epoxide hydrolase; EPHX2 polymorphism; bradykinin; endothelium-derived factors ID PLASMINOGEN ACTIVATOR RELEASE; ISCHEMIC-STROKE; HYPERPOLARIZING FACTORS; BLOOD-PRESSURE; RISK; INHIBITION; POLYMORPHISMS; BRADYKININ; POPULATION; RESISTANCE AB Cytochrome P450-derived epoxyeicosatrienoic acids are potent vasodilators in preclinical models and are hydrolyzed by soluble epoxide hydrolase (EPHX2). Associations between the EPHX2 Lys55Arg and Arg287Gln polymorphisms and cardiovascular disease risk have been reported; however, their impact on vascular function in humans has not been investigated. In 265 volunteers (198 white, 67 black American), forearm blood flow was measured by strain-gauge venous occlusion plethysmography at baseline and in response to bradykinin, methacholine, and sodium nitroprusside. Forearm vascular resistance was calculated as mean arterial pressure/forearm blood flow. In white Americans, Lys55Arg genotype was associated with vasodilator response to bradykinin, such that forearm blood flow was significantly lower (P=0.043) and forearm vascular resistance was significantly higher (P=0.013) in Arg55 variant allele carriers compared to wild-type individuals. Significant associations were also observed with methacholine and sodium nitroprusside. In contrast, no relationship was observed in black Americans. In black Americans, Arg287Gln genotype was associated with vasodilator response to bradykinin. Although the difference in forearm blood flow did not reach statistical significance (P=0.058), forearm vascular resistance was significantly lower (P=0.037) in Gln287 variant allele carriers compared to wild-type individuals. Significant associations were also observed with methacholine and sodium nitroprusside. In white Americans, Gln287 variant allele carriers did not exhibit significantly higher forearm blood flow (P=0.128) or lower forearm vascular resistance (P=0.080). Genetic variation in EPHX2 is associated with forearm vasodilator responses in a bradykinin receptor-and endothelium-independent manner, suggesting an important role for soluble epoxide hydrolase in the regulation of vascular function in humans. (Hypertension. 2011; 57:116-122.) C1 [Lee, Craig R.; Schuck, Robert N.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27599 USA. [Burch, Lauranell H.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Pretorius, Mias] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN USA. [Bartlett, Jackie; Williams, Scott M.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN USA. [Brown, Nancy J.] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN USA. [Brown, Nancy J.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Div Clin Pharmacol, Nashville, TN USA. RP Lee, CR (reprint author), Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, CB 7569,Kerr Hall, Chapel Hill, NC 27599 USA. EM craig_lee@unc.edu RI Williams, Scott/B-9491-2012; OI Lee, Craig/0000-0003-3595-5301 FU American Heart Association; National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) [Z01 ES025034]; [HL085740]; [2P01 DK38226]; [5R01 HL065193] FX This publication was made possible by a Beginning Grant-in-Aid from the American Heart Association to C.R.L.; grant HL085740 to M.P.; funds from the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) to D.C.Z. (Z01 ES025034); and grants 2P01 DK38226 and 5R01 HL065193 to N.J.B. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS; the National Heart, Lung, and Blood Institute; or the NIH. NR 32 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2011 VL 57 IS 1 BP 116 EP U309 DI 10.1161/HYPERTENSIONAHA.110.161695 PG 17 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 695AI UT WOS:000285342600019 PM 21098312 ER PT J AU Wothe, D Gaziano, E Sunderji, S Romero, R Kusanovic, JP Rogers, L Hodges-Savola, C Roberts, S Wassenberg, J AF Wothe, Donald Gaziano, Emanuel Sunderji, Shiraz Romero, Roberto Kusanovic, Juan Pedro Rogers, Linda Hodges-Savola, Cheryl Roberts, Sean Wassenberg, James TI Measurement of sVEGF R1 and PIGF in Serum: Comparing Prototype Assays from Beckman Coulter, Inc. to R&D Systems Microplate Assays SO HYPERTENSION IN PREGNANCY LA English DT Article DE Preeclampsia; Angiogenesis; Placental Growth Factor; Soluble Vascular Endothelial Growth Factor; sFlt-1 ID PLACENTAL GROWTH-FACTOR; CIRCULATING ANGIOGENIC FACTORS; SEVERE PREECLAMPSIA; TYROSINE KINASE-1; NORMAL-PREGNANCY; 2ND-TRIMESTER; 1ST-TRIMESTER; HYPERTENSION; PROTEINURIA; ONSET AB Objective. To compare the performance of prototype Access (R) sVEGF R1 and P1GF automated immunoassays from Beckman Coulter to the Quantikine (R) microplate ELISA assays by R&D Systems. Methods. Samples obtained from pregnant women, non-pregnant women and men were assayed according to manufacturers' instructions. Results. Compared to the Quantikine assays, the Access assays demonstrated improved precision, increased sensitivity, broader dynamic ranges, and reduced analysis time. The Access assays were found to be specific for free sVEGF R1 and free P1GF. Conclusion. There was good correlation between the Access and Quantikine assays. Superior performance by Access assays may have important prenatal diagnostic implications. C1 [Rogers, Linda; Hodges-Savola, Cheryl; Roberts, Sean; Wassenberg, James] Beckman Coulter Inc, Chaska, MN 55318 USA. [Wothe, Donald; Gaziano, Emanuel] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Sunderji, Shiraz] Toledo Hosp, Toledo, OH USA. [Romero, Roberto; Kusanovic, Juan Pedro] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Wassenberg, J (reprint author), Beckman Coulter Inc, 1000 Lake Hazeltine Dr,M-S R110B, Chaska, MN 55318 USA. EM jjwassenberg@beckman.com FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX We gratefully acknowledge the technical assistance of James Mendoza, Kristen Jones, Patricia Nunnelly, Adele Wen Golden and Adam Ettl. This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 22 TC 8 Z9 8 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1064-1955 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2011 VL 30 IS 1 BP 18 EP 27 DI 10.3109/10641950903322881 PG 10 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA 720EW UT WOS:000287264200003 PM 20482334 ER PT J AU Seth, S Najafizadeh, L Cressler, JD AF Seth, Sachin Najafizadeh, Laleh Cressler, John D. TI On the RF Properties of Weakly Saturated SiGe HBTs and Their Potential Use in Ultralow-Voltage Circuits SO IEEE ELECTRON DEVICE LETTERS LA English DT Article DE Biomedical telemetry; heterojunction bipolar transistors (HBTs); low-voltage operation; RF circuit design; silicon-germanium (SiGe); SiGe HBTs ID TRANSISTORS AB We investigate, for the first time, the feasibility of operating silicon-germanium (SiGe) heterojunction bipolar transistors (HBTs) in a weakly saturated bias regime to enable ultralow-voltage RF front-end design. Measured dc, ac, and RF characteristics of third-generation high-performance SiGe HBTs operating in weak saturation are presented. Robust RF operation of 0.12 x 6.0 mu m(2) SiGe HBTs are demonstrated in a common-emitter configuration at collector-to-emitter voltages above 0.15 V. A noise figure of 1.33 dB and an input third-order intercept point above -8 dBm for a 3-GHz input tone are achieved at 0.30 V. These results have potential implications for RF circuits used in severely power-constrained systems. C1 [Seth, Sachin; Cressler, John D.] Georgia Inst Technol, Atlanta, GA 30332 USA. [Najafizadeh, Laleh] NIH, Gaithersburg, MD USA. RP Seth, S (reprint author), Georgia Inst Technol, Atlanta, GA 30332 USA. EM sseth3@mail.gatech.edu; najafizadehl@mail.nih.gov; cressler@ece.gatech.edu NR 8 TC 6 Z9 6 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0741-3106 J9 IEEE ELECTR DEVICE L JI IEEE Electron Device Lett. PD JAN PY 2011 VL 32 IS 1 BP 3 EP 5 DI 10.1109/LED.2010.2087313 PG 3 WC Engineering, Electrical & Electronic SC Engineering GA 701ST UT WOS:000285844400001 ER PT J AU Lau, ST Ji, HF Li, XA Ren, W Zhou, QF Shung, KK AF Lau, Sien Ting Ji, Hong Fen Li, Xiang Ren, Wei Zhou, Qifa Shung, K. Kirk TI KNN/BNT Composite Lead-Free Films for High-Frequency Ultrasonic Transducer Applications SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID PIEZOELECTRIC THICK-FILMS; MEDICAL IMAGING APPLICATIONS; PZT; ARRAYS; DESIGN AB Lead-free K(0.5)Na(0.5)NbO(3)/Bi(0.5)Na(0.5)TiO(3) (KNN/BNT) films have been fabricated by a composite sol-gel technique. Crystalline KNN fine powder was dispersed in the BNT precursor solution to form a composite slurry which was then spin-coated onto a platinum-buffered Si substrate. Repeated layering and vacuum infiltration were applied to produce 5-mu m-thick dense composite film. By optimizing the sintering temperature, the films exhibited good dielectric and ferroelectric properties comparable to PZT films. A 193-MHz high-frequency ultrasonic transducer fabricated from this composite film showed a -6-dB bandwidth of approximately 34%. A tungsten wire phantom was imaged to demonstrate the capability of the transducer. C1 [Lau, Sien Ting; Li, Xiang; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Lau, Sien Ting; Li, Xiang; Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Ji, Hong Fen; Ren, Wei] Xi An Jiao Tong Univ, Minist Educ, Key Lab, Elect Mat Res Lab, Xian 710049, Peoples R China. RP Lau, ST (reprint author), Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. EM sienlau@usc.edu RI Lau, Sien-Ting/B-6091-2013 FU NIH [P41-EB2182]; State Key Development Program for Basic Research of China [2008CB617610]; Shaanxi Province International Collaboration Program [2010KW-09] FX This work was financially supported by NIH Grant P41-EB2182, the State Key Development Program for Basic Research of China (Grant No. 2008CB617610), and the Shaanxi Province International Collaboration Program (Grant No. 2010KW-09). NR 22 TC 11 Z9 11 U1 4 U2 32 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JAN PY 2011 VL 58 IS 1 BP 249 EP 254 DI 10.1109/TUFFC.2011.1793 PG 6 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 708TB UT WOS:000286386100026 PM 21244994 ER PT J AU Frascella, J Richardson, KA McLemore, GL AF Frascella, Joseph Richardson, Kimberlei A. McLemore, Gabrielle L. TI Animal Models of Drug Addiction in Support of Novel Therapeutic Strategies Introduction SO ILAR JOURNAL LA English DT Editorial Material C1 [Frascella, Joseph] NIDA, Div Clin Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. [Richardson, Kimberlei A.] Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. [McLemore, Gabrielle L.] Morgan State Univ, Dept Biol, Baltimore, MD 21239 USA. RP Richardson, KA (reprint author), Howard Univ, Coll Med, Dept Pharmacol, 520 W St NW, Washington, DC 20059 USA. EM kimberlei.richardson@howard.edu NR 70 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 IS 3 BP 233 EP 238 DI 10.1093/ilar.52.3.233 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA V27QM UT WOS:000208627700001 PM 23382141 ER PT J AU Hopf, FW Sparta, DR Bonci, A AF Hopf, F. Woodward Sparta, Dennis R. Bonci, Antonello TI Translational Models of Interactions Between Stress and Alcohol Consumption: Strengths and Limitations SO ILAR JOURNAL LA English DT Article DE alcoholism; aversion resistance; compulsion; molecular mechanism; neuroadaptation; relapse; risk factor; rodent model; sensitization; stress AB Much has been written about the interaction of stressors (physical, social, and psychological) and alcohol addiction based on studies in humans and preclinical models. We begin by considering the significance and complexity of alcoholism and the options for effectively modeling it in animals, particularly rodents. We then focus on the following aspects of stress-alcohol interactions: (1) compulsive alcohol consumption, characterized by continued intake despite the presence of stressful or aversive consequences; (2) the possible relationship between acute stress and increased alcohol intake; (3) an apparent cross sensitization of stress and alcohol exposure, which increases both future reactivity to stress and the risk of developing alcohol addiction; and (4) efforts to target stress in therapeutic interventions for alcoholism. We also describe possible neuroadaptations and genetic factors that may interact with stress to increase susceptibility to alcoholism. Throughout, we describe the challenges and inconsistencies inherent in both human and animal studies of alcoholism, its etiology, and its impacts. We believe the relationship between preclinical and human studies is of paramount importance to understand addiction-related behavior in humans and to direct, improve, and expand animal models. It is our hope that a full understanding of the mechanistic bases of pathological alcohol intake will have translational benefits for the development of behavioral and pharmacological therapies. C1 [Hopf, F. Woodward] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA. [Sparta, Dennis R.] Univ N Carolina, Chapel Hill, NC USA. [Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD USA. RP Hopf, FW (reprint author), Univ Calif San Francisco, Dept Neurol, Ernest Gallo Clin & Res Ctr, 5858 Horton St,Suite 200, Emeryville, CA 94608 USA. EM woody@gallo.ucsf.edu FU National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [RO1AA015358]; State of California for medical research for alcohol and substance abuse through the University of California, San Francisco FX This work was supported by a grant from the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism (RO1AA015358; Hopf) and funds provided by the State of California for medical research for alcohol and substance abuse through the University of California, San Francisco (Bonci). NR 154 TC 6 Z9 6 U1 5 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 IS 3 BP 239 EP 250 DI 10.1093/ilar.52.3.239 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA V27QM UT WOS:000208627700002 PM 23382142 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI Animal Welfare and Scientific Research: 1985 to 2010 October 25, 2010 SO ILAR JOURNAL LA English DT Editorial Material C1 [Brown, Patricia] Natl Inst Hlth, Off Lab Anim Welf, Bethesda, MD 20892 USA. [Gipson, Chester] Anim & Plant Hlth Inspect Serv, USDA, Washington, DC USA. RP Brown, P (reprint author), Natl Inst Hlth, Off Lab Anim Welf, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 417 EP 418 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300001 ER PT J AU Garnett, N AF Garnett, Nelson TI Introduction: By Ladies and Gentlemen, for Ladies and Gentlemen SO ILAR JOURNAL LA English DT Editorial Material C1 [Garnett, Nelson] Natl Inst Hlth, Off Lab Anim Welf, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 419 EP 421 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300002 ER PT J AU McCullough, W AF McCullough, Willie TI Animal Facility Improvement Project Funding SO ILAR JOURNAL LA English DT Article C1 Natl Inst Hlth, Off Construct Grants, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP McCullough, W (reprint author), Natl Inst Hlth, Off Construct Grants, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 428 EP 429 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300007 ER PT J AU Taylor, J AF Taylor, James TI Institutional Animal Care and Use Committees: Session Introduction SO ILAR JOURNAL LA English DT Editorial Material C1 [Taylor, James] Natl Inst Hlth, Off Anim Care & Use, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 434 EP 434 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300010 ER PT J AU Collins, J AF Collins, Jerry TI The Future: Continuing IACUC Challenges SO ILAR JOURNAL LA English DT Article C1 [Collins, Jerry] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Collins, Jerry] Natl Inst Hlth, IPA, Div Policy & Educ, Off Lab Anim Welf, Bethesda, MD 20892 USA. RP Collins, J (reprint author), Yale Univ, Sch Med, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 439 EP 442 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300013 ER PT J AU Silk, S AF Silk, Susan TI The Role of Education in Self-Evaluation SO ILAR JOURNAL LA English DT Article C1 Natl Inst Hlth, Div Policy & Educ, Off Lab Anim Welf, Bethesda, MD 20892 USA. RP Silk, S (reprint author), Natl Inst Hlth, Div Policy & Educ, Off Lab Anim Welf, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 448 EP 449 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300017 ER PT J AU Brown, P AF Brown, Patricia TI Veterinary Care: Session Introduction SO ILAR JOURNAL LA English DT Editorial Material C1 Natl Inst Hlth, Off Lab Anim Welf, Bethesda, MD 20892 USA. RP Brown, P (reprint author), Natl Inst Hlth, Off Lab Anim Welf, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 451 EP 451 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300019 ER PT J AU Schwindaman, D Miller, J AF Schwindaman, Dale Miller, John TI Synergy of Working Together SO ILAR JOURNAL LA English DT Article C1 [Schwindaman, Dale] Anim & Plant Hlth Inspect Serv, USDA, Washington, DC USA. [Miller, John] Natl Inst Hlth, Off Protect Res Risks, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 469 EP 473 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300025 ER PT J AU Nakamura, R AF Nakamura, Richard TI Animal Models and Basic Science-Bench to Bedside SO ILAR JOURNAL LA English DT Article C1 NIMH, Div Intramural Res Programs, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Nakamura, R (reprint author), NIMH, Div Intramural Res Programs, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 493 EP 498 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300036 ER PT J AU Kurilla, M AF Kurilla, Michael TI Animal Models Facilitate Rapid Responses to Emerging Infectious Diseases SO ILAR JOURNAL LA English DT Article C1 [Kurilla, Michael] NIAID, Off BioDef Res Affairs, Bethesda, MD 20892 USA. [Kurilla, Michael] NIAID, Div Microbiol & Infect Dis, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kurilla, M (reprint author), NIAID, Off BioDef Res Affairs, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1084-2020 J9 ILAR J JI ILAR J. PY 2011 VL 52 SU S BP 501 EP 506 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA V29IO UT WOS:000208742300038 ER PT S AU Wiegand, G Xin, H Anderson, A Mullinax, J Jaiswal, K Wiegand, A Avital, I AF Wiegand, G. Xin, H. Anderson, A. Mullinax, J. Jaiswal, K. Wiegand, A. Avital, Itzhak BE Farkas, DL Nicolau, DV Leif, RC TI Cellular Spectroscopy: Applications to Cancer Stem Cell Charecterization SO IMAGING, MANIPULATION, AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX CY JAN 22-25, 2011 CL San Francisco, CA SP SPIE DE cancer stem cells; rare event analysis; multi-spectral imaging AB Spectroscopic and light scattering methods were used to gain insight into the existence and characterization of the cancer stem cell. Fundamental technical description of devices used have been reported elsewhere. We included alterations and implementation of these biophotonic instruments as applied to our objectives. We disassociated human tumor and submitted the cells to optical characterization to support our working hypothesis of stem cell origins to cancer and mechanisms. Single cell combined with population based analysis within the Pancreatic cancer system led us to information regarding the polarization state of cells possessing anchor proteins and drug influx pumps. Multispectral imaging combined with flow cytometry enabled us to target rare cells that appear to retain template DNA. rendering them resistant to anti-cancer drug therapy. In this study we describe an optical method that combines high-throughput population pattern and correlates each cell with an individual fluorescent and bright-field image. C1 [Wiegand, G.; Xin, H.; Anderson, A.; Mullinax, J.; Jaiswal, K.; Avital, Itzhak] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Wiegand, G (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wiegandg@mail.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-439-0 J9 PROC SPIE PY 2011 VL 7902 AR 79021G DI 10.1117/12.875458 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BXZ27 UT WOS:000297677500035 ER PT B AU Patronas, NJ AF Patronas, N. J. BE Drevelegas, A TI Brain Metastasis SO IMAGING OF BRAIN TUMORS WITH HISTOLOGICAL CORRELATIONS, SECOND EDITION LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE-SPECTROSCOPY; H-1 MR-SPECTROSCOPY; CEREBRAL BLOOD-FLOW; SHORT ECHO TIME; NEPHROGENIC SYSTEMIC FIBROSIS; INTRACRANIAL MASS LESIONS; HIGH-DOSE GADOTERIDOL; HIGH-GRADE GLIOMAS; COMPUTED-TOMOGRAPHY C1 NIH, Bethesda, MD 20892 USA. RP Patronas, NJ (reprint author), NIH, Bethesda, MD 20892 USA. EM npatronas@nih.gov NR 145 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-540-87648-9 PY 2011 BP 373 EP 400 DI 10.1007/978-3-540-87650-2_13 D2 10.1007/978-3-540-87650-2 PG 28 WC Oncology; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BTG44 UT WOS:000286903300013 ER PT S AU Kothapalli, N Fugmann, SD AF Kothapalli, Nagarama Fugmann, Sebastian D. BE Rast, JP Booth, JWD TI Characterizing Somatic Hypermutation and Gene Conversion in the Chicken DT40 Cell System SO IMMUNE RECEPTORS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE DT40; Somatic hypermutation; Gene conversion; AID; Gene targeting; Immunoglobulin ID DIVERSIFICATION; LINE; TOOL AB The secondary immunoglobulin gene diversification processes, somatic hypermutation (SHM), immunoglobulin gene conversion (GCV), and class switch recombination, are important for efficient humoral immune responses. They require the action of activation-induced cytidine deaminase, an enzyme that deaminates cytosine in the context of single-stranded DNA. The chicken DT40 B-cell line is an important model system for exploring the mechanisms of SHM and GCV, as both processes occur constitutively without the need for stimulation. In addition, standard gene targeting strategies can be used for defined manipulations of the DT40 genome. Thus, these cells represent an excellent model of choice for genetic studies of SHM and GCV. Problems arising from defects in early B-cell development that are of concern when using genetically engineered mice are avoided in this system. Here, we describe how to perform gene targeting in DT40 cells and how to determine the effects of such modifications on SHM and GCV. C1 [Kothapalli, Nagarama; Fugmann, Sebastian D.] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. RP Kothapalli, N (reprint author), NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. OI Kothapalli, Naga Rama/0000-0001-7993-8525 FU Intramural NIH HHS NR 13 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-138-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 748 BP 255 EP 271 DI 10.1007/978-1-61779-139-0_18 D2 10.1007/978-1-61779-139-0 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BVW59 UT WOS:000292990200018 PM 21701980 ER PT B AU Yewdell, JW Bennink, JR AF Yewdell, Jonathan W. Bennink, Jack R. BE Kaufmann, SHE Rouse, BT Sacks, DL TI Overview of Viral Pathogens SO IMMUNE RESPONSE TO INFECTION LA English DT Article; Book Chapter ID DNA VIRUSES; MECHANISMS; APOPTOSIS; RECEPTORS; ENTRY; CHEMOKINES; INFECTION; NUCLEUS; DISEASE; CELLS C1 [Yewdell, Jonathan W.; Bennink, Jack R.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. NR 39 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-514-1 PY 2011 BP 133 EP 141 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BSQ56 UT WOS:000285482300011 ER PT B AU Sacks, DL AF Sacks, David L. BE Kaufmann, SHE Rouse, BT Sacks, DL TI Suppression of Immune Responses to Protozoan Parasites SO IMMUNE RESPONSE TO INFECTION LA English DT Article; Book Chapter ID REGULATORY T-CELLS; EXPERIMENTAL CEREBRAL MALARIA; TRYPANOSOMA-CRUZI INFECTION; HUMAN DENDRITIC CELLS; CHAGAS-DISEASE; CUTANEOUS LEISHMANIASIS; PLASMODIUM INFECTION; FUNCTIONAL-CHARACTERISTICS; VISCERAL LEISHMANIASIS; SIGNALING PATHWAYS C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sacks, DL (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 74 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 978-1-55581-514-1 PY 2011 BP 441 EP 451 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BSQ56 UT WOS:000285482300036 ER PT B AU Holland, SM AF Holland, Steven M. BE Kaufmann, SHE Rouse, BT Sacks, DL TI Genetics of Antibacterial Host Defenses SO IMMUNE RESPONSE TO INFECTION LA English DT Article; Book Chapter ID SEVERE CONGENITAL NEUTROPENIA; CHRONIC GRANULOMATOUS-DISEASE; ADENYLATE KINASE 2; CYSTIC-FIBROSIS; BACTERIAL-INFECTIONS; CLINICAL-FEATURES; DEFICIENCY CAUSES; MUTATIONS; INVOLVEMENT; DISORDERS C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-514-1 PY 2011 BP 473 EP 482 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BSQ56 UT WOS:000285482300038 ER PT J AU Lee, JB Oelke, M Ramachandra, L Canaday, DH Schneck, JP AF Lee, Jessica B. Oelke, Mathias Ramachandra, Lakshmi Canaday, David H. Schneck, Jonathan P. TI Decline of influenza-specific CD8(+) T cell repertoire in healthy geriatric donors SO IMMUNITY & AGEING LA English DT Article AB Background: While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8(+) T cells. Studying the CD8+ T cell response to influenza epitopes is crucial in understanding the disease associated morbidity and mortality especially in at risk populations such as the elderly. We compared the CD8+ T cell response to immunodominant and subdominant influenza epitopes in HLA-A2(+) control, adult donors, aged 21-42, and in geriatric donors, aged 65 and older. Results: We used a novel artificial Antigen Presenting Cell (aAPC) based stimulation assay to reveal responses that could not be detected by enzyme-linked immunosorbent spot (ELISpot). 14 younger control donors and 12 geriatric donors were enrolled in this study. The mean number of influenza-specific subdominant epitopes per control donor detected by ELISpot was only 1.4 while the mean detected by aAPC assay was 3.3 (p = 0.0096). Using the aAPC assay, 92% of the control donors responded to at least one subdominant epitopes, while 71% of control donors responded to more than one subdominant influenza-specific response. 66% of geriatric donors lacked a subdominant influenza-specific response and 33% of geriatric donors responded to only 1 subdominant epitope. The difference in subdominant response between age groups is statistically significant (p = 0.0003). Conclusion: Geriatric donors lacked the broad, multi-specific response to subdominant epitopes seen in the control donors. Thus, we conclude that aging leads to a decrease in the subdominant influenza-specific CTL responses which may contribute to the increased morbidity and mortality in older individuals. C1 [Lee, Jessica B.; Oelke, Mathias; Schneck, Jonathan P.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Ramachandra, Lakshmi] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. [Ramachandra, Lakshmi] NIAID, Sci Review Program, Div Extramural Act, NIH, Bethesda, MD 20892 USA. [Canaday, David H.] Cleveland VA, Geriatr Res Educ & Clin Ctr, Cleveland, VA 44106 USA. RP Schneck, JP (reprint author), Johns Hopkins Univ, Dept Pathol, 733 N Broadway BRB 632, Baltimore, MD 21205 USA. EM jschnec1@jhmi.edu OI Oelke, Mathias/0000-0003-2253-6167 FU National Institutes of Health [AI44129, CA108835, AI077097, PO1 AI072677, AI077056]; VA FX This work was supported by National Institutes of Health [AI44129, CA108835, AI077097, PO1 AI072677 to JS, AI077056 to LR and DHC], and VA Merit to DHC. NR 41 TC 10 Z9 10 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4933 J9 IMMUN AGEING JI Immun. Ageing PY 2011 VL 8 AR 6 DI 10.1186/1742-4933-8-6 PG 11 WC Geriatrics & Gerontology; Immunology SC Geriatrics & Gerontology; Immunology GA V30IM UT WOS:000208809700006 PM 21846352 ER PT B AU Chong, AY Gorden, P AF Chong, Angeline Y. Gorden, Phillip BE Eisenbarth, GS TI Lessons from Patients with Anti-Insulin Receptor Autoantibodies SO IMMUNOENDOCRINOLOGY: SCIENTIFIC AND CLINICAL ASPECTS SE Contemporary Endocrinology LA English DT Article; Book Chapter DE Type B insulin resistance; Anti-insulin receptorautoantibody; Autoimmunity; Hyperglycemia; Hypoglycemia ID B INSULIN-RESISTANCE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SUCCESSFUL IMMUNOSUPPRESSIVE THERAPY; HODGKINS-DISEASE; ANTIRECEPTOR ANTIBODIES; MONOCLONAL GAMMOPATHY; ACANTHOSIS NIGRICANS; BINDING INHIBITOR; PASSIVE TRANSFER; OVARIAN FAILURE AB Type B insulin resistance is a rare syndrome caused by autoantibodies to the insulin receptor. Patients typically present with severe insulin resistance and hyperglycemia, but some manifest hypoglycemia following a period of hyperglycemia or hypoglycemia alone. The syndrome is predominantly seen in middle-aged black women. Other clinical features of type B insulin resistance are acanthosis nigricans, hyperandrogenism in premenopausal women, autoimmune disorders, proteinuric renal disease, and hematologic abnormalities. In addition to dysglycemia, the metabolic characteristics of the syndrome include low scrum triglyceride levels and high adiponectin levels. The autoantibody acts as an agonist at the insulin receptor at low titers, but functions as an antagonist at high titers. The partial agonist properties of the autoantibody are responsible for the spectrum of glycemic states observed in type B insulin resistance. The treatment of type B insulin resistance has been of limited success to date and protocols addressing multiple components of the underlying autoimmune process arc being developed. C1 [Chong, Angeline Y.; Gorden, Phillip] NIDDK, Clin Endocrinol Branch, Clin Res Ctr, NIH, Bethesda, MD USA. RP Chong, AY (reprint author), NIDDK, Clin Endocrinol Branch, Clin Res Ctr, NIH, Bethesda, MD USA. NR 68 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-477-7 J9 CONTEMP ENDOCRINOL S PY 2011 BP 369 EP 383 DI 10.1007/978-1-60327-478-4_22 D2 10.1007/978-1-60327-478-4 PG 15 WC Endocrinology & Metabolism; Immunology SC Endocrinology & Metabolism; Immunology GA BSY64 UT WOS:000286133200022 ER PT B AU Wang, E Marincola, FM AF Wang, Ena Marincola, Francesco M. BE Marincola, FM Wang, E TI From the "Delayed Allergy Reaction" to the "Emmunologic Constant of Rejection" SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter ID TRANSCRIPTION FACTORS; COLORECTAL-CANCER; GENE-EXPRESSION; ALLOGRAFT-REJECTION; HEPATITIS-C; IRF FAMILY; INTERFERON; CHEMOKINES; THERAPY; MICROENVIRONMENT C1 [Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA. RP Wang, E (reprint author), NIH, IDIS, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM ewang@mail.cc.nih.gov; FMarincola@mail.cc.nih.gov; FMarincola@mail.cc.nih.gov; ewang@mail.cc.nih.gov NR 36 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 3 EP 8 DI 10.1007/978-1-4419-7219-4_1 D2 10.1007/978-1-4419-7219-4 PG 6 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300001 ER PT B AU Stewart, CA Trinchieri, G AF Stewart, C. Andrew Trinchieri, Giorgio BE Marincola, FM Wang, E TI Turning on and off the Immunological Switch: Immune Response Polarization and Its Control by IL-10 and STAT3 SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter ID NF-KAPPA-B; REGULATORY T-CELLS; HYPER-IGE SYNDROME; TUMOR-ASSOCIATED MACROPHAGES; INTESTINAL EPITHELIAL-CELLS; TNF-ALPHA PRODUCTION; DENDRITIC CELLS; IN-VIVO; ANTIINFLAMMATORY RESPONSE; INTERLEUKIN-10 RECEPTOR C1 [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. EM trinchig@mail.nih.gov RI Stewart, Charles/G-2470-2012 NR 171 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 27 EP 55 DI 10.1007/978-1-4419-7219-4_4 D2 10.1007/978-1-4419-7219-4 PG 29 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300004 ER PT B AU Krensky, AM Clayberger, C AF Krensky, Alan M. Clayberger, Carol BE Marincola, FM Wang, E TI Chemokines and Cytotoxic Effector Molecules in Rejection SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter DE Chemokine; Cytotoxic T lymphocyte (CTL); Granulysin; Granzymes; Natural killer (NK) cell; Perforin ID RENAL-ALLOGRAFT REJECTION; SECONDARY LYMPHOID ORGANS; MESSENGER-RNA EXPRESSION; T-CELLS; GRANZYME-B; TRANSPLANT REJECTION; GRAFT FUNCTION; NONINVASIVE DIAGNOSIS; KIDNEY-TRANSPLANTS; MULTIPLE-SCLEROSIS AB Increased or de novo expression of chemokines and cytotoxic effector molecules is part of the "immunologic constant of rejection" and are central to the "signature" of broad activation of proinflammatory and cytotoxic cells. Although several chemokines are associated with rejection and provocative results have been obtained in animal models, no real breakthroughs have occurred in translating these findings to clinical transplantation. In contrast, the cytotoxic effector molecules, granulysin, granzymes and perforin have proven to be important biomarkers for rejection. C1 [Krensky, Alan M.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krensky, AM (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM krenskya@mail.nih.gov NR 96 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 77 EP 92 DI 10.1007/978-1-4419-7219-4_6 D2 10.1007/978-1-4419-7219-4 PG 16 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300006 ER PT B AU Castiello, L Sabatino, M Jin, P Marincola, FM Stroncek, D AF Castiello, Luciano Sabatino, Marianna Jin, Ping Marincola, Francesco M. Stroncek, David BE Marincola, FM Wang, E TI Clinical Applications of Activated Immune Cells SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter ID PULSED DENDRITIC CELLS; CD8(+) T-CELLS; CANCER VACCINES; ADOPTIVE TRANSFER; VIVO EXPANSION; CMV INFECTION; BONE-MARROW; CYTOMEGALOVIRUS; TRANSPLANTATION; PEPTIDE C1 [Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov OI Castiello, Luciano/0000-0001-7146-3158 NR 38 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 93 EP 102 DI 10.1007/978-1-4419-7219-4_7 D2 10.1007/978-1-4419-7219-4 PG 10 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300007 ER PT B AU Yamano, Y Jacobson, S AF Yamano, Yoshihisa Jacobson, Steven BE Marincola, FM Wang, E TI HTLV-1 Infected CD4(+)CD25(+)CCR4(+) T-Cells Disregulate Balance of Inflammation and Tolerance in HTLV-1 Associated Neuroinflammatory Disease SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter DE ATL; CD4(+)CD25(+)CCR4(+) T cell; exFoxp3(+) cell; HAM/TSP; HTLV-1; Regulatory T cell ID VIRUS TYPE-I; MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; TRANSCRIPTION FACTOR FOXP3; KAPPA-B SITE; LEUKEMIA-VIRUS; PROVIRAL LOAD; NEUROLOGIC DISEASE; PERIPHERAL-BLOOD; INTERFERON-GAMMA; GENE-EXPRESSION AB HTLV-1 is a T lymphotropic human retrovirus that is the causative agent of adult T cell leukemia/lymphoma and is associated with multiorgan immunological disorders such as chronic myelitis, uveitis, Sjogren syndrome, bronchoalveolitis, arthritis, and polymyositis. HTLV-1 infection of T-cells induces a variety of abnormalities such as cellular activation, proinflammatory changes, and proliferation. Here, we discuss the mechanism of HTLV-1 infection-induced immune dysregulation. Since the majority of autoimmune diseases are of unknown etiology, the discovery of HTLV-1 and its association with these immunological disorders has greatly enhanced our understanding of the pathogenic mechanisms of organ-specific immune abnormalities. C1 [Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 189 EP 198 DI 10.1007/978-1-4419-7219-4_12 D2 10.1007/978-1-4419-7219-4 PG 10 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300012 ER PT B AU Pos, Z Galon, J AF Pos, Zoltan Galon, Jerome BE Marincola, FM Wang, E TI D/2 Predictors of Favorable Outcome in Cancer SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter ID RENAL-CELL CARCINOMA; TUMOR-INFILTRATING LYMPHOCYTES; LONG-TERM SURVIVAL; CYTOTOXIC T-CELLS; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; TELOMERE LENGTH; ADVANCED-STAGE; IMMUNE CELLS; LUNG-CANCER C1 [Pos, Zoltan] NIH, Infect Dis & Immunogent Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Pos, Zoltan] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. RP Pos, Z (reprint author), NIH, Infect Dis & Immunogent Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM posz@cc.nih.gov NR 49 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 199 EP 210 DI 10.1007/978-1-4419-7219-4_13 D2 10.1007/978-1-4419-7219-4 PG 12 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300013 ER PT B AU Hakim, FT AF Hakim, Frances T. BE Marincola, FM Wang, E TI Chronic Graft Versus Host Disease: Inflammation at the Crossroads of Allo and Auto Immunity SO IMMUNOLOGIC SIGNATURES OF REJECTION LA English DT Article; Book Chapter DE Chronic graft versus host disease; Hematopoietic stem cell transplantation; Type 1 interferon; Plasmacytoid dendritic cells; Tumor derived growth factor beta; Th1, Th2, Th17, regulatory T cells ID STEM-CELL TRANSPLANTATION; REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CONSENSUS DEVELOPMENT PROJECT; PLASMACYTOID DENDRITIC CELLS; SALIVARY-GLAND DYSFUNCTION; WORKING GROUP-REPORT; GENE-EXPRESSION; HUMAN SCLERODERMA AB The mechanisms underlying the pathogenesis of chronic graft versus host disease (CGVHD) remain obscure, despite the clinical importance of this disorder in transplant recipients. In this chapter we review current evidence and theories concerning the two main aspects of CGVHD: the development of inflammatory infiltrates that target epithelia and the initiation of extensive fibrosis. We further address the effects of transplantation on Treg cells and on central tolerance. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hakim, FT (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. EM hakimf@mail.nih.gov NR 120 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7218-7 PY 2011 BP 259 EP 280 DI 10.1007/978-1-4419-7219-4_17 D2 10.1007/978-1-4419-7219-4 PG 22 WC Oncology SC Oncology GA BSH95 UT WOS:000284503300017 ER PT J AU Douek, DC Nabel, GJ AF Douek, Daniel C. Nabel, Gary J. TI Vaccines SO IMMUNOLOGICAL REVIEWS LA English DT Editorial Material C1 [Douek, Daniel C.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Douek, DC (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 3509,MSC 3022, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov NR 15 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 5 EP 7 DI 10.1111/j.1600-065X.2010.00986.x PG 3 WC Immunology SC Immunology GA 700TE UT WOS:000285766400001 PM 21198661 ER PT J AU Moss, B AF Moss, Bernard TI Smallpox vaccines: targets of protective immunity SO IMMUNOLOGICAL REVIEWS LA English DT Review DE B cells; T cells; viral; antibodies; cell surface molecules; vaccination ID EXTRACELLULAR ENVELOPED VIRUS; NEUTRALIZING MONOCLONAL-ANTIBODIES; HUMAN DENDRITIC CELLS; 2 INFECTIOUS FORMS; CD8(+) T-CELLS; SECONDARY POXVIRUS INFECTION; COMPLEMENT CONTROL PROTEINS; GREEN FLUORESCENT PROTEIN; SURFACE HEPARAN-SULFATE; VIRION MEMBRANE-PROTEIN AB The eradication of smallpox, one of the great triumphs of medicine, was accomplished through the prophylactic administration of live vaccinia virus, a comparatively benign relative of variola virus, the causative agent of smallpox. Nevertheless, recent fears that variola virus may be used as a biological weapon together with the present susceptibility of unimmunized populations have spurred the development of new-generation vaccines that are safer than the original and can be produced by modern methods. Predicting the efficacy of such vaccines in the absence of human smallpox, however, depends on understanding the correlates of protection. This review outlines the biology of poxviruses with particular relevance to vaccine development, describes protein targets of humoral and cellular immunity, compares animal models of orthopoxvirus disease with human smallpox, and considers the status of second- and third-generation smallpox vaccines. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,Room 1E13C 1,33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM brnoss@nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX I thank David Tscharke and Linda Wyatt for comments on the study. Preparation of the review was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 276 TC 58 Z9 58 U1 3 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 8 EP 26 DI 10.1111/j.1600-065X.2010.00975.x PG 19 WC Immunology SC Immunology GA 700TE UT WOS:000285766400002 PM 21198662 ER PT J AU Klebanoff, CA Acquavella, N Yu, ZY Restifo, NP AF Klebanoff, Christopher A. Acquavella, Nicolas Yu, Zhiya Restifo, Nicholas P. TI Therapeutic cancer vaccines: are we there yet? SO IMMUNOLOGICAL REVIEWS LA English DT Review DE cell intrinsic modulators of metabolism and memory formation; Toll-like receptor agonist; CTLA-4; PD-1; Wnt; beta-catenin; mTOR ID CD8(+) T-CELLS; COLONY-STIMULATING FACTOR; STAGE-IV MELANOMA; PHASE-II TRIAL; REFRACTORY PROSTATE-CANCER; INCOMPLETE FREUNDS-ADJUVANT; RANDOMIZED CONTROLLED-TRIAL; MYELOID SUPPRESSOR-CELLS; LOADED DENDRITIC CELLS; VERSUS-HOST-DISEASE AB Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer-based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront: (i) a corrupted tumor microenvironment containing regulatory T cells and aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor targets capable of antigen loss and immune evasion. Future progress may come from innovations in the development of selective preparative regimens that eliminate or neutralize suppressive cellular populations, more effective immunologic adjuvants, and further refinement of agents capable of antagonizing immune check-point blockade pathways. C1 [Klebanoff, Christopher A.; Acquavella, Nicolas; Yu, Zhiya; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, NIH, Mark O Hatfield Clin Res Ctr, Room 3West 5816,10 Ctr Dr, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/D-9581-2011; OI Restifo, Nicholas P./0000-0003-4229-4580 FU U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research. The authors thank Christopher Scott and Megan Bachinski for reading and editing of the manuscript. NR 209 TC 135 Z9 140 U1 3 U2 34 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 27 EP 44 DI 10.1111/j.1600-065X.2010.00979.x PG 18 WC Immunology SC Immunology GA 700TE UT WOS:000285766400003 PM 21198663 ER PT J AU Graham, BS AF Graham, Barney S. TI Biological challenges and technological opportunities for respiratory syncytial virus vaccine development SO IMMUNOLOGICAL REVIEWS LA English DT Review DE respiratory syncytial virus; vaccine; protein structure; gene-based vector; animal model; enhanced disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; ATTACHMENT GLYCOPROTEIN-G; CELL-MEDIATED-IMMUNITY; TOXIC T-CELLS; PULMONARY EOSINOPHILIA; FUSION PROTEIN; RSV INFECTION; YOUNG-CHILDREN; COTTON RATS; NEUTRALIZING ANTIBODY AB Respiratory syncytial virus (RSV) is an important cause of respiratory disease causing high rates of hospitalizations in infants, significant morbidity in children and adults, and excess mortality in the elderly. Major barriers to vaccine development include early age of RSV infection, capacity of RSV to evade innate immunity, failure of RSV-induced adaptive immunity to prevent reinfection, history of RSV vaccine-enhanced disease, and lack of an animal model fully permissive to human RSV infection. These biological challenges, safety concerns, and practical issues have significantly prolonged the RSV vaccine development process. One great advantage compared to other difficult viral vaccine targets is that passively administered neutralizing monoclonal antibody is known to protect infants from severe RSV disease. Therefore, the immunological goals for vaccine development are to induce effective neutralizing antibody to prevent infection and to avoid inducing T-cell response patterns associated with enhanced disease. Live-attenuated RSV and replication-competent chimeric viruses are in advanced clinical trials. Gene-based strategies, which can control the specificity and phenotypic properties of RSV-specific T-cell responses utilizing replication-defective vectors and which may improve on immunity from natural infection, are progressing through preclinical testing. Atomic level structural information on RSV envelope glycoproteins in complex with neutralizing antibodies is guiding design of new vaccine antigens that may be able to elicit RSV-specific antibody responses without induction of RSV-specific T-cell responses. These new technologies may allow development of vaccines that can protect against RSV-mediated disease in infants and establish a new immunological paradigm in the host to achieve more durable protection against reinfection. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 2502,MSC-3017, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU National Institute of Allergy and Infectious Diseases, NIH FX The constructive comments of Peter Collins, Julie Ledgerwood, Jie Liu, Jason McLellan, Tracy Ruckwardt, and Robert Seder are appreciated. This work was supported by intramural funding from the National Institute of Allergy and Infectious Diseases, NIH. NR 136 TC 110 Z9 114 U1 5 U2 23 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 149 EP 166 DI 10.1111/j.1600-065X.2010.00972.x PG 18 WC Immunology SC Immunology GA 700TE UT WOS:000285766400010 PM 21198670 ER PT J AU Hickman, HD Bennink, JR Yewdell, JW AF Hickman, Heather D. Bennink, Jack R. Yewdell, Jonathan W. TI From optical bench to cageside: intravital microscopy on the long road to rational vaccine design SO IMMUNOLOGICAL REVIEWS LA English DT Review DE intravital microscopy; sympathetic nervous system; T cell; vaccine; virus ID CD8-ALPHA(+) DENDRITIC CELLS; CD8(+) T-CELLS; SUBCAPSULAR SINUS MACROPHAGES; DRAINING LYMPH-NODES; SUBSETS IN-VIVO; B-CELLS; ANTIGEN PRESENTATION; IMMUNE-SYSTEM; CUTTING EDGE; VIRUS-INFECTION AB No antiviral vaccine is perfect. For some important pathogens, there are no effective vaccines. Many current vaccines are based on the working principles of Jenner and Pasteur, that is, empiric administration of attenuated or inactivated forms of the pathogen. Tapping the full potential of vaccination requires a thorough understanding of the mechanism of immune activation by pathogens and their individual components. Though the rate of discovery continues to accelerate, the complexity of the immune system is daunting, particularly when integrated into the overall physiology of the host. Here, we review the application of multiphoton microscopy to examine host-pathogen interactions, focusing on our recent efforts to understand mouse CD8+ T-cell responses to viruses at the level of cellular interactions in lymph nodes draining the infection site. We also discuss our recent efforts to understand the influence of the sympathetic nervous system on antiviral immunity, with the ultimate goal of appreciating the traditional elements of immunity as just one facet of the total organismal response to infection and immunization. C1 [Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,Room 2E19,33 N Dr, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS [ZIA AI001053-03] NR 124 TC 4 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 209 EP 220 DI 10.1111/j.1600-065X.2010.00973.x PG 12 WC Immunology SC Immunology GA 700TE UT WOS:000285766400014 PM 21198674 ER PT J AU Bethony, JM Cole, RN Guo, XT Kamhawi, S Lightowlers, MW Loukas, A Petri, W Reed, S Valenzuela, JG Hotez, PJ AF Bethony, Jeffrey M. Cole, Rhea N. Guo, Xiaoti Kamhawi, Shaden Lightowlers, Marshall W. Loukas, Alex Petri, William Reed, Steven Valenzuela, Jesus G. Hotez, Peter J. TI Vaccines to combat the neglected tropical diseases SO IMMUNOLOGICAL REVIEWS LA English DT Review DE neglected tropical diseases; tropical diseases; vaccines; parasitic vaccines ID TRANSMITTED HELMINTH INFECTIONS; CANINE VISCERAL LEISHMANIASIS; CD4(+) T-CELLS; ENTAMOEBA-HISTOLYTICA INFECTION; INTESTINAL NEMATODE INFECTIONS; ATTENUATED SCHISTOSOME VACCINE; HOOKWORM NECATOR-AMERICANUS; DEFINED RECOMBINANT ANTIGEN; ACID-BINDING PROTEIN; L-MAJOR INFECTION AB The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world's poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access. C1 [Bethony, Jeffrey M.; Hotez, Peter J.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Cole, Rhea N.; Reed, Steven] Infect Dis Res Inst, Seattle, WA USA. [Guo, Xiaoti] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Lightowlers, Marshall W.] Univ Melbourne, Melbourne, Vic, Australia. [Loukas, Alex] James Cook Univ, Cairns, Qld, Australia. [Petri, William] Univ Virginia, Charlottesville, VA USA. [Hotez, Peter J.] Sabin Vaccine Inst, Washington, DC USA. RP Bethony, JM (reprint author), George Washington Univ, Med Ctr, Ross Hall 727,2300 Eye St NW, Washington, DC 20037 USA. EM mtmjmb@gwumc.edu RI Loukas, Alex/B-7355-2014; Lightowlers, Marshall/L-5966-2015; OI Loukas, Alex/0000-0002-0896-8441; Lightowlers, Marshall/0000-0002-6655-0086; Hotez, Peter/0000-0001-8770-1042 FU Bill and Melinda Gates Foundation through the Sabin Vaccine Institute; Wellcome Trust [075818]; Australian National Health and Medical Research Council [350279, 400109, 628320] FX J. M. B. and P. J. H. are funded by the Bill and Melinda Gates Foundation through the Sabin Vaccine Institute. Research funding (M. W. L) from the Wellcome Trust grant 075818 and the Australian National Health and Medical Research Council grants 350279, 400109, 628320. NR 281 TC 79 Z9 81 U1 3 U2 43 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 237 EP 270 DI 10.1111/j.1600-065X.2010.00976.x PG 34 WC Immunology SC Immunology GA 700TE UT WOS:000285766400016 PM 21198676 ER PT J AU Madan, RA Gulley, JL AF Madan, Ravi A. Gulley, James L. TI Therapeutic cancer vaccine fulfills the promise of immunotherapy in prostate cancer SO IMMUNOTHERAPY LA English DT Article DE immunotherapy; metastatic prostate cancer; minimal toxicity; overall survival; therapeutic cancer vaccine ID SIPULEUCEL-T; ACID-PHOSPHATASE; DENDRITIC CELLS; END-POINTS; MITOXANTRONE; PREDNISONE; DOCETAXEL; ANTIGEN; TRIAL; IRRADIATION AB Evaluation of: Kantoff PW, Higano CS, Shore ND et al.: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411-422 (2010). For many years, preclinical and clinical studies have attempted to harness the power of the immune system and focus it on malignant cells in an attempt to improve clinical outcomes for patients with cancer. This paper describes the landmark Phase III trial that led to the first US FDA approval of a therapeutic cancer vaccine. In a randomized trial of 512 patients, those treated with sipuleucel-T survived for 25.8 months compared with those treated with placebo, who survived 21.7 months (HR: 0.78; p = 0.03). There was, however, no change in time to progression, which may relate to the underlying mechanism of this new class of therapeutics. C1 [Madan, Ravi A.; Gulley, James L.] NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. [Madan, Ravi A.; Gulley, James L.] NCI, Canc Res Ctr, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, 10 Ctr Dr,8809 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU NIH; National Cancer Institute and Center for Cancer Research FX The authors acknowledge the Intramural Research Program of the NIH, National Cancer Institute and Center for Cancer Research for their support of this study. The authors also thank Bonnie L Casey for her editorial assistance in the preparation of this manuscript. NR 33 TC 4 Z9 4 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X EI 1750-7448 J9 IMMUNOTHERAPY-UK JI Immunotherapy PD JAN PY 2011 VL 3 IS 1 BP 27 EP 31 DI 10.2217/IMT.10.77 PG 5 WC Immunology SC Immunology GA 720HC UT WOS:000287270400011 PM 21174555 ER PT J AU Bornstein, MH Hahn, CS Suwalsky, JTD Haynes, OM AF Bornstein, Marc H. Hahn, Chun-Shin Suwalsky, Joan T. D. Haynes, O. Maurice TI MATERNAL AND INFANT BEHAVIOR AND CONTEXT ASSOCIATIONS WITH MUTUAL EMOTION AVAILABILITY SO INFANT MENTAL HEALTH JOURNAL LA English DT Article ID RELIABILITY; ATTACHMENT; RESPONSIVENESS; SENSITIVITY; AGREEMENT; SCALES; CONTINUITY; REGRESSION; CONSTRUCT; KAPPA AB Emotional availability (EA) is a prominent index of mutual socioemotional adaptation in the parent-infant dyad. This study examines zero-order and unique associations of multiple maternal and infant behavior and context indicators to variation in aspects of EA in mothers and their young infants. The associations to each were explored in separate analyses for maternal sensitivity and infant responsiveness in 369 European American mothers and their firstborn 5 1/2-month-olds. Beyond zero-order relations, robust regression analyses revealed differentiated patterns of unique relations of mother and infant behavior and context indicators to the EA dimensions of maternal sensitivity and infant responsiveness. Although potential behavior and context relations to EA are many, prominent relations to maternal sensitivity and infant responsiveness are few, and patterns of association vary for the two dimensions of EA. Adequate EA is fundamental to a healthy parent-infant relationship, and understanding the behavior and context indicators associated with EA is fundamental to its enhancement. C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Suwalsky, Joan T. D.; Haynes, O. Maurice] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 93 TC 4 Z9 5 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0163-9641 J9 INFANT MENT HEALTH J JI Infant Ment. Health J. PD JAN-FEB PY 2011 VL 32 IS 1 SI SI BP 70 EP 94 DI 10.1002/imhj.20284 PG 25 WC Psychology, Developmental SC Psychology GA 710ZP UT WOS:000286555800006 ER PT J AU Okugawa, S Moayeri, M Eckhaus, MA Crown, D Miller-Randolph, S Liu, SH Akira, S Leppla, SH AF Okugawa, Shu Moayeri, Mahtab Eckhaus, Michael A. Crown, Devorah Miller-Randolph, Sharmina Liu, Shihui Akira, Shizuo Leppla, Stephen H. TI MyD88-Dependent Signaling Protects against Anthrax Lethal Toxin-Induced Impairment of Intestinal Barrier Function SO INFECTION AND IMMUNITY LA English DT Article ID CAPILLARY MORPHOGENESIS PROTEIN-2; BACILLUS-ANTHRACIS; BACTERIAL TRANSLOCATION; GASTROINTESTINAL-TRACT; MACROPHAGE SENSITIVITY; MYD88-DEFICIENT MICE; IRRADIATED MICE; IN-VIVO; INFECTION; RECEPTOR AB MyD88-deficient mice were previously shown to have increased susceptibility to Bacillus anthracis infection relative to wild-type animals. To determine the mechanism by which MyD88 protects against B. anthracis infection, knockout mice were challenged with nonencapsulated, toxigenic B. anthracis or with anthrax toxins. MyD88-deficient mice had increased susceptibility to B. anthracis and anthrax lethal toxin but not to edema toxin. Lethal toxin alone induced marked multifocal intestinal ulcers in the knockout animals, compromising the intestinal epithelial barrier. The resulting enteric bacterial leakage in the knockout animals led to peritonitis and septicemia. Focal ulcers and erosion were also found in MyD88-heterozygous control mice but with far lower incidence and severity. B. anthracis infection also induced a similar enteric bacterial septicemia in MyD88-deficient mice but not in heterozygous controls. We show that lethal toxin and B. anthracis challenge induce bacteremia as a result of intestinal damage in MyD88-deficient mice. These results suggest that loss of the intestinal epithelial barrier and enteric bacterial septicemia may contribute to sensitizing MyD88-deficient mice to B. anthracis and that MyD88 plays a protective role against lethal toxin-induced impairment of intestinal barrier. C1 [Okugawa, Shu; Moayeri, Mahtab; Crown, Devorah; Miller-Randolph, Sharmina; Liu, Shihui; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. [Eckhaus, Michael A.] NIH, Diagnost & Res Serv Branch, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Akira, Shizuo] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan. RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, 33 North Dr,Bldg 33,Rm 1W20B, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov RI Akira, Shizuo/C-3134-2009 FU NIH, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 42 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2011 VL 79 IS 1 BP 118 EP 124 DI 10.1128/IAI.00963-10 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 697WJ UT WOS:000285550200010 PM 20974827 ER PT J AU Mori, N Ueda, A Geleziunas, R Wada, A Hirayama, T Yoshimura, T Yamamoto, N AF Mori, Naoki Ueda, Atsuhisa Geleziunas, Romas Wada, Akihiro Hirayama, Toshiya Yoshimura, Teizo Yamamoto, Naoki TI Induction of Monocyte Chemoattractant Protein 1 by Helicobacter pylori Involves NF-kappa B (Retraction of vol 69, pg 1280, 2001) SO INFECTION AND IMMUNITY LA English DT Correction C1 [Mori, Naoki] Nagasaki Univ, Inst Trop Med, Dept Prevent Med & AIDS Res, Nagasaki 852, Japan. Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 232, Japan. Gladstone Inst Virol & Immunol, San Francisco, CA USA. NCI, Immunopathol Sect, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Mori, N (reprint author), Nagasaki Univ, Inst Trop Med, Dept Prevent Med & AIDS Res, Nagasaki 852, Japan. NR 1 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2011 VL 79 IS 1 BP 543 EP 543 DI 10.1128/IAI.01066-10 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 697WJ UT WOS:000285550200054 ER PT J AU Esona, MD Banyai, K Foytich, K Freeman, M Mijatovic-Rustempasic, S Hull, J Kerin, T Steele, AD Armah, GE Geyer, A Page, N Agbaya, VA Forbi, JC Aminu, M Gautam, R Seheri, LM Nyangao, J Glass, R Bowen, MD Gentsch, JR AF Esona, M. D. Banyai, K. Foytich, K. Freeman, M. Mijatovic-Rustempasic, S. Hull, J. Kerin, T. Steele, A. D. Armah, G. E. Geyer, A. Page, N. Agbaya, V. A. Forbi, J. C. Aminu, M. Gautam, R. Seheri, L. M. Nyangao, J. Glass, R. Bowen, M. D. Gentsch, J. R. TI Genomic characterization of human rotavirus G10 strains from the African Rotavirus Network: Relationship to animal rotaviruses SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Gastroenteritis; Genome configuration; Reassortment; Zoonotic origin ID POLYMERASE CHAIN-REACTION; DIVERSITY; GENOTYPE; IDENTIFICATION; CLASSIFICATION; PROGRAMS; DIARRHEA; INDIA AB Global rotavirus surveillance has led to the detection of many unusual human rotavirus (HRV) genotypes. The aim of this study was to elucidate the genetic and evolutionary relationships of short fragments of all 11 gene segments of G10 HRV strains identified in West Africa through the African Rotavirus Network (ARN) system. During 1998-2004 surveillance within the ARN, we identified 5 G10 P[8] HRV strains. Fragments of all 11 gene segments of these G10 strains were sequenced. Phylogenetic and sequence analyses of each gene segment revealed high nucleotide similarities amongst the ARN strains (97-100%) except in the case of the VP1(85-96%) and NSP2 genes (87.8-99.7%) where some strains were divergent. All genes of the ARN strains were classified as Wa-like (genotype 1) with the exception of their VP7 gene of all strains (genotype G10) and the VP6 gene of a single strain, 6755/2002/ARN (DS-1 like, genotype 2). While classified as Wa-like, the NSP2 genes of four of the ARN strains occupied a distinct sub-lineage related to simian strain Tuch, while the NSP2 of strain 6755/2002/ARN and NSP5 genes of all strains were closely related to the cognate genes of both human and animal strains belonging to the Wa-like genogroup. Although these findings help to elucidate the evolution of ARN G10 strains, additional sequence studies of cognate animal rotavirus genes are needed to determine irrefutably the specific origin of those genes relative to both human and animal rotavirus strains. Published by Elsevier B.V. C1 [Esona, M. D.; Banyai, K.; Foytich, K.; Freeman, M.; Mijatovic-Rustempasic, S.; Hull, J.; Kerin, T.; Gautam, R.; Bowen, M. D.; Gentsch, J. R.] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Atlanta, GA USA. [Banyai, K.] Hungarian Acad Sci, Vet Med Res Inst, H-1581 Budapest, Hungary. [Steele, A. D.] PATH, Seattle, WA USA. [Armah, G. E.] Noguchi Mem Res Inst Accra, Accra, Ghana. [Geyer, A.; Seheri, L. M.] Univ Limpopo, MRC DPRU, Limpopo, South Africa. [Page, N.] Natl Inst Communicable Dis, Viral Gastroenteritis Unit, Johannesburg, South Africa. [Agbaya, V. A.] Inst Pasteur Cote dIvoire DVE, Lab Bacteriol Virol, Abidjan, Cote Ivoire. [Forbi, J. C.] Innovat Biotech, Virol Lab, Keffi Abjua, Nigeria. [Aminu, M.] Ahmadu Bello Univ Zaria, Dept Microbiol, Zaria, Nigeria. [Nyangao, J.] Kenya Res Inst, Virus Res Ctr, Nairobi, Kenya. [Glass, R.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Esona, MD (reprint author), 1600 Clifton Rd NE,Mail Stop G-04, Atlanta, GA 30333 USA. EM mdi4@cdc.gov OI Page, Nicola/0000-0001-5845-4417; Banyai, Krisztian/0000-0002-6270-1772 FU World Health Organization; Centers for Disease Control and Prevention; Association of Public Health Laboratories in Silver Spring, Maryland FX The post doctoral fellowship of Dr. Mathew Dioh Esona was provided through the Rotavirus Vaccine Program, a collaboration between the Program for Appropriate Technology in Health, The World Health Organization and the Centers for Disease Control and Prevention. Dr. Banyai Krisztian was an International Emerging Infectious Diseases Fellow supported by the Association of Public Health Laboratories in Silver Spring, Maryland in partnership with the Centers for Disease Control and Prevention. Our sincere thanks also go to all the staff of the MRC/Diarrhoeal Pathogens Research Unit, University of Limpopo and the Gastroenteritis and Respiratory Viruses Laboratory Branch at CDC, Atlanta, GA, USA for their invaluable assistance. NR 20 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JAN PY 2011 VL 11 IS 1 BP 237 EP 241 DI 10.1016/j.meegid.2010.09.010 PG 5 WC Infectious Diseases SC Infectious Diseases GA 711AT UT WOS:000286558800031 PM 20934537 ER PT J AU de Filippis, I Gopalan, V Huyen, Y AF de Filippis, Ivano Gopalan, Vivek Huyen, Yentram TI PorA VR3 Typing Database: A web-based resource for the determination of PorA VR3 alleles of Neisseria meningitidis SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Neisseria meningitidis; PorA; Variable regions; VR3 database ID MENINGOCOCCI AB The variable regions (VR) of the surface-exposed PorA protein of Meningococci are used for subtyping and are considered the most abundant epitopes of outer membrane vesicle-based vaccine preparations. We have developed both a database that maintains all the known VR3 alleles and a web-based application for the rapid identification and submission of new VR3 variants based on sequence comparison. (C) 2010 Elsevier B.V. All rights reserved. C1 [de Filippis, Ivano] Fiocruz MS, Inst Nacl Controle Qualidade Saude, BR-21045900 Rio De Janeiro, Brazil. [Gopalan, Vivek; Huyen, Yentram] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. RP de Filippis, I (reprint author), Fiocruz MS, Inst Nacl Controle Qualidade Saude, Av Brasil 4365, BR-21045900 Rio De Janeiro, Brazil. EM ivano.defilippis@incqs.fiocruz.br NR 10 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JAN PY 2011 VL 11 IS 1 BP 248 EP 249 DI 10.1016/j.meegid.2010.08.011 PG 2 WC Infectious Diseases SC Infectious Diseases GA 711AT UT WOS:000286558800033 PM 20801234 ER PT J AU Clarke, MA Cage, JC Ajenifuja, KO Wentzensen, NA Adepiti, AC Wacholder, S Burk, RD Schiffman, M AF Clarke, Megan A. Gage, Julia C. Ajenifuja, Kayode O. Wentzensen, Nicolas A. Adepiti, Akinfolarin C. Wacholder, Sholom Burk, Robert D. Schiffman, Mark TI A population-based cross-sectional study of age-specific risk factors for high risk human papillomavirus prevalence in rural Nigeria SO INFECTIOUS AGENTS AND CANCER LA English DT Article AB Background: Cervical cancer, caused by persistent infection with carcinogenic human papillomavirus (HR-HPV), is particularly prevalent in Sub-Saharan Africa and is associated with a high mortality rate. Some studies in West Africa, including our own, have found unusually high HR-HPV across all ages with a slight peak in older women. This increased prevalence at older ages may complicate screen-and-treat programs, which are implemented in regions where HPV prevalence declines with age and typically target women between 30-49 years. A better understanding of the determinants of high HR-HPV prevalence at older ages is needed. The goal of this study is to explore risk factors for HR-HPV prevalence by age among women in our population-based study in Irun, a rural town in southwestern Nigeria. Methods: 1,420 women were administered a clinic-based questionnaire regarding sexual and reproductive behavior, marital status (including co-wives), and malaria exposure. Logistic regression compared questionnaire responses and PCR positivity for a set of 13 carcinogenic HR-HPV types. Results were stratified by age (15-29, 30-45, 46-55, and 56+ years). Results: Birth control use and age at first pregnancy were associated with HR-HPV (p-value = 0.03 and 0.05, respectively). Early age at sexual debut and multiple sex partners were risks for HR-HPV, but did not reach significance (p-value = 0.1 and 0.07, respectively). Neither self-reported malaria nor presence of co-wives in the household was associated with HR-HPV (p-value = 0.85 and 0.24, respectively). In age sub-categories, early age at sexual debut was a significant risk factor for HR-HPV among women 35-45 years (p-value = 0.02). Early age at first pregnancy remained a significant risk factor for women aged 56+ years (p-value = 0.04). Greater than 2 sex partners and use of birth control were associated (though not significantly) with HR-HPV in women aged 30-45 (p-value = 0.08, respectively). Conclusions: In this high-risk region with elevated HR-HPV prevalence at older ages, we confirmed previously described, behavioral determinants of HR-HPV. There was no association with self-reported malaria or co-wives, which we had hypothesized might correlate with HR-HPV at older ages. C1 [Clarke, Megan A.; Gage, Julia C.; Wentzensen, Nicolas A.; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Ajenifuja, Kayode O.; Adepiti, Akinfolarin C.] Obafemi Awolowo Univ, Dept Obstet Gynaecol & Perinatol, Ife, Nigeria. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Obstet, Bronx, NY 10467 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Gynecol & Womens Hlth, Bronx, NY 10467 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. RP Clarke, MA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM clarkma2@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services, NIH [5U01CA078527-13]; NIH [HHSN261200900303P] FX Supported by the intramural program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, NIH grant 5U01CA078527-13 and NIH contract #HHSN261200900303P NR 24 TC 10 Z9 10 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-9378 J9 INFECT AGENTS CANCER JI Infect. Agents Cancer PY 2011 VL 6 AR UNSP 12 DI 10.1186/1750-9378-6-12 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA V30DI UT WOS:000208796300012 PM 21801395 ER PT J AU Maskew, M MacPhail, AP Whitby, D Egger, M Wallis, CL Fox, MP AF Maskew, Mhairi MacPhail, A. Patrick Whitby, Denise Egger, Matthias Wallis, Carole L. Fox, Matthew P. TI Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa SO INFECTIOUS AGENTS AND CANCER LA English DT Article DE Kaposi sarcoma; Kaposi sarcoma herpes virus; resource-poor setting; antiretroviral therapy AB Background: Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. Results: We analyzed cross-sectional data collected from 404 HIV-infected treatment-nave adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm(3)) and CD4 (90 vs. 80 cells/mm(3)) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable. Conclusions: We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease. C1 [Maskew, Mhairi; MacPhail, A. Patrick] Univ Witwatersrand, Clin HIV Res Unit, Dept Med, Fac Hlth Sci, ZA-2193 Johannesburg, South Africa. [Maskew, Mhairi; Fox, Matthew P.] Univ Witwatersrand, Hlth Econ & Epidemiol Res Off, Dept Med, Fac Hlth Sci, ZA-2192 Johannesburg, South Africa. [MacPhail, A. Patrick] Right Care, ZA-2192 Johannesburg, South Africa. [Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21702 USA. [Egger, Matthias] Univ Bern Finkenhubelweg, Div Int & Environm Hlth, Inst Social & Prevent Med ISPM, CH-3012 Bern, Switzerland. [Wallis, Carole L.] Univ Witwatersrand, Dept Mol Med & Hematol, Fac Hlth Sci, ZA-2193 Johannesburg, South Africa. [Fox, Matthew P.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02118 USA. [Fox, Matthew P.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA. RP Maskew, M (reprint author), Univ Witwatersrand, Clin HIV Res Unit, Dept Med, Fac Hlth Sci, York Ave, ZA-2193 Johannesburg, South Africa. EM mmaskew@witshealth.co.za OI Fox, Matthew/0000-0001-9887-0634; MASKEW, MHAIRI/0000-0003-4238-0200 FU United States Agency for International Development (USAID) [674-A-00-08-00007-00]; National Institute of Allergy and Infectious Diseases (NIAID); Right to Care (RTC); NGO FX We express our gratitude to the directors and staff of the Themba Lethu Clinic, in addition to Right to Care (RTC), the NGO supporting the database and study site through a partnership with USAID. We also thank the Gauteng and National Department of Health for providing for the care of the patients at the Themba Lethu Clinic as part of the Comprehensive Care Management and Treatment plan and Lynne Mcnamara for proofing of the manuscript. This work was supported by the United States Agency for International Development (USAID) under the terms of agreement 674-A-00-08-00007-00 with RTC. MF was also supported by Award Number K01AI083097 from the National Institute of Allergy and Infectious Diseases (NIAID). The content is solely the responsibility of the authors and does not necessarily represent the official views of the USAID, the Themba Lethu Clinic, Right to Care or National Institute of Allergy And Infectious Diseases. USAID and NIAID had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript. NR 53 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-9378 J9 INFECT AGENTS CANCER JI Infect. Agents Cancer PY 2011 VL 6 AR UNSP 22 DI 10.1186/1750-9378-6-22 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA V30DI UT WOS:000208796300022 PM 22093140 ER PT J AU Mbulaiteye, SM Bhatia, K Adebamowo, C Sasco, AJ AF Mbulaiteye, Sam M. Bhatia, Kishor Adebamowo, Clement Sasco, Annie J. TI HIV and cancer in Africa: mutual collaboration between HIV and cancer programs may provide timely research and public health data SO INFECTIOUS AGENTS AND CANCER LA English DT Review AB The eruption of Kaposi sarcoma (KS) and aggressive non-Hodgkin lymphoma (NHL) in young homosexual men in 1981 in the West heralded the onset of the human immunodeficiency virus (HIV) infection epidemic, which remains one of the biggest challenges to global public health and science ever. Because KS and NHL were increased > 10,000 and 50-600 times, respectively, with HIV, they were designated AIDS defining cancers (ADC). Cervical cancer (CC), increased 5-10 times was also designated as an ADC. A few other cancers are elevated with HIV, including Hodgkin lymphoma (10 times), anal cancer (15-30 times), and lung cancer (4 times) are designated as non-AIDS defining cancers (NADCs). Since 1996 when combination antiretroviral therapy (cART) became widely available in the West, dramatic decreases in HIV mortality have been observed and substantial decrease in the incidence of ADCs. Coincidentally, the burden of NADCs has increased as people with HIV age with chronic HIV infection. The impact of HIV infection on cancer in sub-Saharan Africa, where two thirds of the epidemic is concentrated, remains poorly understood. The few studies conducted indicate that risks for ADCs are also increased, but quantitatively less so than in the West. The risks for many cancers with established viral associations, including liver and nasopharynx, which are found in Africa, do not appear to be increased. These data are limited because of competing mortality, and cancer is under diagnosed, pathological confirmation is rare, and cancer registration not widely practiced. The expansion of access to life-extending cART in sub-Saharan Africa, through programs such as the Global Fund for AIDS, Malaria, and Tuberculosis and the US President's Emergency Program for AIDS Relief (PEPFAR), is leading to dramatic lengthening of life of HIV patients, which will likely influence the spectrum and burden of cancer in patients with HIV. In this paper, we review current literature and explore merits for integrating cancer research in established HIV programs to obtain timely data about the incidence and burden of cancer in HIV-infected persons in Africa. C1 [Mbulaiteye, Sam M.; Bhatia, Kishor] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. [Adebamowo, Clement] Univ Maryland, Inst Human Virol, Sch Med, Baltimore, MD 21201 USA. [Sasco, Annie J.] Bordeaux Segalen Univ, Team HIV Canc & Global Hlth Resource Ltd Countrie, Inserm U 897, Bordeaux, France. RP Mbulaiteye, SM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov OI Adebamowo, Clement/0000-0002-6571-2880 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This work was funded, in part, by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. We thank the organizers of the 12th Conference of the Institute of Human Virology, Tropea, Calabria, Italy for inviting us to speak. NR 132 TC 20 Z9 20 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-9378 J9 INFECT AGENTS CANCER JI Infect. Agents Cancer PY 2011 VL 6 AR UNSP 16 DI 10.1186/1750-9378-6-16 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA V30DI UT WOS:000208796300016 PM 22004990 ER PT J AU Safaeian, M Gao, YT Sakoda, LC Quraishi, SM Rashid, A Wang, BS Chen, JB Pruckler, J Mintz, E Hsing, AW AF Safaeian, Mahboobeh Gao, Yu-Tang Sakoda, Lori C. Quraishi, Sabah M. Rashid, Asif Wang, Bing-Shen Chen, Jinbo Pruckler, James Mintz, Eric Hsing, Ann W. TI Chronic typhoid infection and the risk of biliary tract cancer and stones in Shanghai, China SO INFECTIOUS AGENTS AND CANCER LA English DT Article AB Previous studies have shown a positive association between chronic typhoid carriage and biliary cancers. We compared serum Salmonella enterica serovar Typhi antibody titers between biliary tract cancer cases, biliary stone cases without evidence of cancer, and healthy subjects in a large population-based case-control study in Shanghai, China. Participants included 627 newly diagnosed primary biliary tract cancer patients; 1,037 biliary stone cases (774 gallbladder and 263 bile-duct) and 959 healthy subjects without a history of cancer, randomly selected from the Shanghai Resident Registry. Overall only 6/2,293 (0.26%) were Typhi positive. The prevalence of Typhi was 1/457 (0.22%), 4/977 (0.41%), and 1/859 (0.12%) among cancer cases, biliary-stone cases, and population controls, respectively. We did not find an association between Typhi and biliary cancer in Shanghai, due to the very low prevalence of chronic carriers in this population. The low seroprevalence of S. Typhi in Shanghai is unlikely to explain the high incidence of biliary cancers in this population. C1 [Safaeian, Mahboobeh; Quraishi, Sabah M.; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai Canc Inst, Shanghai, Peoples R China. [Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wang, Bing-Shen] Shanghai Med Univ, Dept Surg, Zhongshan Hosp, Shanghai 200032, Peoples R China. [Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Pruckler, James; Mintz, Eric] Ctr Dis Control & Prevent, Diarrheal Dis Epidemiol Sect, Foodborne & Diarrheal Dis Branch, Atlanta, GA USA. RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM safaeianm@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX We thank Jie Deng, Jiarong Cheng, Lu Sun, Kai Wu, and the staff at the Shanghai Cancer Institute for data collection, specimen collection, and processing, surgeons at the collaborating hospitals for data collection, and local pathologists for pathology review; Shelley Niwa of Westat for data preparation and management; and Janis Koci of the Scientific Applications International Corporation for management of the biological samples. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the reviews or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 9 TC 4 Z9 4 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-9378 J9 INFECT AGENTS CANCER JI Infect. Agents Cancer PY 2011 VL 6 AR UNSP 6 DI 10.1186/1750-9378-6-6 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA V30DI UT WOS:000208796300006 PM 21535882 ER PT J AU Wakeham, K Webb, EL Sebina, I Muhangi, L Miley, W Johnson, WT Ndibazza, J Elliott, AM Whitby, D Newton, R AF Wakeham, Katie Webb, Emily L. Sebina, Ismail Muhangi, Lawrence Miley, Wendell Johnson, W. Thomas Ndibazza, Juliet Elliott, Alison M. Whitby, Denise Newton, Robert TI Parasite infection is associated with Kaposi's sarcoma associated herpesvirus (KSHV) in Ugandan women SO INFECTIOUS AGENTS AND CANCER LA English DT Article AB Background: Immune modulation by parasites may influence susceptibility to bacteria and viruses. We examined the association between current parasite infections, HIV and syphilis (measured in blood or stool samples using standard methods) and antibodies against Kaposi's sarcoma herpesvirus (KSHV), measured by ELISA, in 1915 stored plasma samples from pregnant women in Entebbe, Uganda. Results: Seroprevalence of KSHV was higher in women with malaria parasitaemia (73% vs 60% p = 0.01), hookworm (67% vs 56% p = 0.001) and Mansonella perstans (69% vs 59% p = 0.05); seroprevalence increased with increasing intensity of hookworm infection (p < 0.001[ trend]). No associations were found for HIV, five other parasites or active syphilis. These effects were not explained by socioeconomic status or education. Conclusions: Specific parasite infections are associated with presence of antibodies against KSHV, perhaps mediated via their effect on immune function. C1 [Wakeham, Katie; Sebina, Ismail; Muhangi, Lawrence; Ndibazza, Juliet; Elliott, Alison M.] Uganda Virus Res Inst, Coinfect Studies Programme, Med Res Council, Uganda Res Unit AIDS, Entebbe, Uganda. [Wakeham, Katie; Johnson, W. Thomas; Newton, Robert] Univ York, Epidemol & Genet Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Miley, Wendell; Whitby, Denise] Univ London London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London WC1E 7HT, England. [Miley, Wendell; Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21702 USA. [Elliott, Alison M.] Univ London London Sch Hyg & Trop Med, Dept Clin Res, London WC1E 7HT, England. [Newton, Robert] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England. RP Wakeham, K (reprint author), Uganda Virus Res Inst, Coinfect Studies Programme, Med Res Council, Uganda Res Unit AIDS, POB 49, Entebbe, Uganda. EM katiewakeham@gmail.com OI Webb, Emily/0000-0002-4019-7456; Elliott, Alison/0000-0003-2818-9549 FU Wellcome Trust [090132, 064693]; National Cancer Institute, National Institutes of Health, Department of Health and Human Services [HHSN261200800001E] FX Wellcome Trust as a PhD Training Fellowship held by KW (grant number 090132), a Wellcome Trust Senior Fellowship held by AME (grant number 064693) and funded in part by the Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services (contract HHSN261200800001E). Wellcome Trust is a UK registered charity No. 210183. We thank all the participants and the staff of the Entebbe Mother and Baby Study and the staff of the laboratory and statistics departments of the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS who made this study possible. NR 52 TC 12 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-9378 J9 INFECT AGENTS CANCER JI Infect. Agents Cancer PY 2011 VL 6 AR UNSP 15 DI 10.1186/1750-9378-6-15 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA V30DI UT WOS:000208796300015 PM 21962023 ER PT J AU Zuna, RE Tuller, E Wentzensen, N Mathews, C Allen, RA Shanesmith, R Dunn, ST Gold, MA Wang, SS Walker, J Schiffman, M AF Zuna, Rosemary E. Tuller, Erin Wentzensen, Nicolas Mathews, Cara Allen, Richard A. Shanesmith, Rebecca Dunn, S. Terence Gold, Michael A. Wang, Sophia S. Walker, Joan Schiffman, Mark TI HPV16 variant lineage, clinical stage, and survival in women with invasive cervical cancer SO INFECTIOUS AGENTS AND CANCER LA English DT Article DE cervical neoplasms; human papillomavirus 16; HPV16 variants AB Background: HPV16 variants are associated with different risks for development of CIN3 and invasive cancer, although all are carcinogenic. The relationship of HPV 16 variants to cancer survival has not been studied. Methods: 155 HPV16-positive cervical cancers were categorized according to European and non-European variant patterns by DNA sequencing of the E6 open reading frame. Clinico-pathologic parameters and clinical outcome were collected by chart review and death registry data. Results: Of the 155 women (mean age 44.7 years; median follow-up 26.7 months), 85.2% harbored European variants while 14.8% had non-European sequences. HPV16 variants differed by histologic cell type (p = 0.03) and stage (1 vs. 2+; p = 0.03). Overall, 107 women (68.0%) were alive with no evidence of cancer, 42 (27.1%) died from cervical cancer, 2 (1.3%) were alive with cervical cancer, and 4 (2.6%) died of other causes. Death due to cervical cancer was associated with European variant status (p < 0.01). While 31% of women harboring tumors with European variants died from cervical cancer during follow-up, only 1 of 23 (4.4%) non-European cases died of cancer. The better survival for non-European cases was partly mediated by lower stage at diagnosis. Conclusions: Overall, invasive cervical cancers with non-European variants showed a less aggressive behavior than those with European variants. These findings should be replicated in a population with more non-European cases. C1 [Zuna, Rosemary E.; Allen, Richard A.; Shanesmith, Rebecca; Dunn, S. Terence; Gold, Michael A.] Univ Oklahoma, Dept Pathol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Tuller, Erin; Mathews, Cara; Gold, Michael A.; Walker, Joan] Univ Oklahoma, Dept Obstet & Gynecol, Div Gynecol Oncol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Wentzensen, Nicolas; Wang, Sophia S.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Tuller, Erin] Univ Missouri Hlth Syst, Dept Obstet & Gynecol, Columbia, MO 65203 USA. [Shanesmith, Rebecca] Tulane Univ Hlth Sci, Dept Pathol & Lab Med, New Orleans, LA 70112 USA. [Gold, Michael A.] Vanderbilt Univ, Dept Obstet & Gynecol, Med Ctr, Nashville, TN 37232 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA. [Wang, Sophia S.] Beckman Inst, Duarte, CA 91010 USA. RP Zuna, RE (reprint author), Univ Oklahoma, Dept Pathol, Hlth Sci Ctr, 940 SL Young Blvd, Oklahoma City, OK 73104 USA. EM rosemary-zuna@ouhsc.edu FU Oklahoma Center for the Advancement of Science and Technology [OCAST HR05-136]; National Cancer Institute [03-A117523, N02-CP-31102]; National Institutes of Health FX This study was supported by grants from the Oklahoma Center for the Advancement of Science and Technology (OCAST HR05-136) and from the National Cancer Institute (03-A117523) as well as from contract N02-CP-31102 from the National Cancer Institute. Drs. Wentzensen and Schiffman are supported by the Intramural Research Program of the National Institutes of Health. Special thanks are due to Greg Rydzak, Information Management Services, Silver Spring, MD for his assistance in data analysis as well as to Tracey Young and her associates in the Department of Obstetrics and Gynecology and Susan Nagelhout, CTR of the OU Medical Center Tumor Registry for their efforts in obtaining patient follow-up information. NR 25 TC 14 Z9 14 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1750-9378 J9 INFECT AGENTS CANCER JI Infect. Agents Cancer PY 2011 VL 6 AR UNSP 19 DI 10.1186/1750-9378-6-19 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA V30DI UT WOS:000208796300019 PM 22035468 ER PT B AU Ginexi, EM Robertson, EB AF Ginexi, Elizabeth M. Robertson, Elizabeth B. BE Bardo, MT Fishbein, DH Milich, R TI Translating Research on Inhibitory Control for the Prevention of Drug Abuse SO INHIBITORY CONTROL AND DRUG ABUSE PREVENTION: FROM RESEARCH TO TRANSLATION LA English DT Article; Book Chapter ID AGED FOSTER-CHILDREN; SCHOOL READINESS; EXECUTIVE FUNCTIONS; SELF-REGULATION; BEHAVIORAL-REGULATION; EFFORTFUL CONTROL; EARLY-CHILDHOOD; INTERVENTION; KINDERGARTEN; ACHIEVEMENT AB Significant progress has been made in effective approaches to the prevention of drug abuse over the past few decades. Many of the existing evidence-based prevention programs promote social and emotional learning, an approach that addresses underlying causes of problem behavior while supporting academic achievement and promoting positive youth development. There is growing recognition that these programs may work, at least in part, because of their impacts on underlying neurocognitive systems during important developmental periods in childhood. The development of the neural systems that support self-regulatory functions is important for acquiring appropriate neurocognitive skills that affect risk for mental, emotional, and behavioral disorders. This edited volume reviews the state of our knowledge about the neurobiological and psychosocial processes involved in behavioral inhibitory capacity and provides insights into how these findings may be translated into interventions. C1 [Ginexi, Elizabeth M.; Robertson, Elizabeth B.] NIDA, Div Epidemiol Serv & Prevent Res, Prevent Res Branch, Bethesda, MD 20892 USA. RP Ginexi, EM (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, Prevent Res Branch, Bethesda, MD 20892 USA. EM LGinexi@mail.nih.gov NR 33 TC 1 Z9 2 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-1267-1 PY 2011 BP 3 EP 9 DI 10.1007/978-1-4419-1268-8_1 D2 10.1007/978-1-4419-1268-8 PG 7 WC Psychology, Clinical; Substance Abuse; Medicine, General & Internal SC Psychology; Substance Abuse; General & Internal Medicine GA BUR10 UT WOS:000290131200001 ER PT J AU Reindl, W Bowen, BP Balamotis, MA Green, JE Northen, TR AF Reindl, Wolfgang Bowen, Benjamin P. Balamotis, Michael A. Green, Jeffrey E. Northen, Trent R. TI Multivariate analysis of a 3D mass spectral image for examining tissue heterogeneity SO INTEGRATIVE BIOLOGY LA English DT Article ID TUMOR MICROENVIRONMENT; MAMMARY-GLAND; SPECTROMETRY; CANCER; BRAIN AB The tissue microenvironment critically influences the molecular characteristics of a tumor. However, as tumorous tissue is highly heterogeneous it may harbor various sub-populations with different microenvironments, greatly complicating the unambiguous analysis of tumor biology. Mass spectrometry imaging techniques allow for the direct analysis of tumors in the spatial context of their microenvironment. However, discovery of heterogeneous sub-populations often depends on the use of multivariate statistical methods. While this is routinely used for 2D images, multivariate statistical approaches are rarely seen in the context of 3D images. Here we present the automatic alignment of 2D images recorded by nanostructure-initiator mass spectrometry (NIMS) to reconstruct a 3D model of a mouse mammary tumor. Multivariate statistical analysis was applied to the whole 3D reconstruction at once, revealing distinct tumor regions, an observation that would not have been possible in such clarity through the analysis of isolated 2D sections. These sub-structures were confirmed by H&E and Oil Red O stains. This study shows that the combination of 3D imaging and multivariate statistics can be used to define tumor regions. C1 [Reindl, Wolfgang; Bowen, Benjamin P.; Northen, Trent R.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Bioenergy GTL & Struct Biol, Div Life Sci, Berkeley, CA 94720 USA. [Balamotis, Michael A.] Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Genome Dynam, Div Life Sci, Berkeley, CA 94720 USA. [Green, Jeffrey E.] NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Reindl, W (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Bioenergy GTL & Struct Biol, Div Life Sci, Berkeley, CA 94720 USA. EM TRNorthen@lbl.gov RI Northen, Trent/K-3139-2012; OI Northen, Trent/0000-0001-8404-3259 FU Department of Energy Low Dose Radiation SFA [DE-AC02-05CH11231]; Bay Area Breast Cancer SPORE [P50 CA 58207]; California Breast Cancer Research Program [15IB-0063]; National Institutes of Health; Center for Cancer Research; National Cancer Institute; Forschungsstipendium of the Deutsche Forschungsgemeinschaft (DFG) [RE 3108/1-1] FX We gratefully acknowledge support from the Department of Energy Low Dose Radiation SFA [DE-AC02-05CH11231], Bay Area Breast Cancer SPORE [P50 CA 58207], and from the California Breast Cancer Research Program [15IB-0063]. This work was supported in part by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, National Cancer Institute and a Forschungsstipendium of the Deutsche Forschungsgemeinschaft (DFG) [RE 3108/1-1] to W. R. We thank Sandhya Bhatnagar for helping with the H&E stains and Dr Zi-yao Liu for assisting with animal preparation. NR 29 TC 10 Z9 10 U1 0 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2011 VL 3 IS 4 BP 460 EP 467 DI 10.1039/c0ib00091d PG 8 WC Cell Biology SC Cell Biology GA 745GT UT WOS:000289154600018 PM 21212877 ER PT J AU Serge, A de Keijzer, S Van Hemert, F Hickman, MR Hereld, D Spaink, HP Schmidt, T Snaar-Jagalska, BE AF Serge, Arnauld de Keijzer, Sandra Van Hemert, Freek Hickman, Mark R. Hereld, Dale Spaink, Herman P. Schmidt, Thomas Snaar-Jagalska, B. Ewa TI Quantification of GPCR internalization by single-molecule microscopy in living cells SO INTEGRATIVE BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; DICTYOSTELIUM-DISCOIDEUM CELLS; LIGAND-INDUCED PHOSPHORYLATION; SURFACE CAMP RECEPTORS; CYCLIC-AMP RECEPTORS; CHEMOATTRACTANT RECEPTORS; SIGNAL-TRANSDUCTION; DOWN-REGULATION; 7-TRANSMEMBRANE RECEPTORS; CAR1 AB Receptor internalization upon ligand stimulation is a key component of a cell's response and allows a cell to correctly sense its environment. Novel fluorescent methods have enabled the direct visualization of the agonist-stimulated G-protein-coupled receptors (GPCR) trafficking in living cells. However, it is difficult to observe internalization of GPCRs in vivo due to intrinsic autofluorescence and cytosolic signals of fluorescently labeled GPCRs. This study uses the superior positional accuracy of single-molecule fluorescence microscopy to visualize in real time the internalization of Dictyostelium discoideum cAMP receptors, cAR1, genetically encoded with eYFP. This technique made it possible to follow the number of receptors in time revealing that the fraction of cytosolic receptors increases after persistent agonist stimulation and that the majority of the receptors were degraded after internalization. The observed internalization process was phosphorylation dependent, as shown with the use of a phosphorylation deficient cAR1 mutant, cm1234-eYFP, or stimulation with an antagonist, Rp-cAMPS that does not induce receptor phosphorylation. Furthermore, experiments done in mound-stage cells suggest that intrinsic, phosphorylation-induced internalization of cAR1 is necessary for Dictyostelium wild type cells to progress properly through multicellular development. To our knowledge, this observation illustrates for the first time phosphorylation-dependent internalization of single cAR1 molecules in living cells and its involvement in multicellular development. This very sensitive imaging of receptor internalization can be a useful and universal approach for pharmacological characterization of GPCRs in other cell types. C1 [Serge, Arnauld; de Keijzer, Sandra; Van Hemert, Freek; Schmidt, Thomas] Leiden Univ, Leiden Inst Phys, Leiden, Netherlands. [de Keijzer, Sandra; Van Hemert, Freek; Spaink, Herman P.; Snaar-Jagalska, B. Ewa] Leiden Univ, IBL Mol Cell Biol, Gorlaeus Lab, NL-2333 CC Leiden, Netherlands. [Hickman, Mark R.] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. [Hereld, Dale] NIAAA, Div Metab & Hlth Effects, Rockville, MD 20852 USA. RP Serge, A (reprint author), Leiden Univ, Leiden Inst Phys, POB 9504, Leiden, Netherlands. EM B.E.Snaar-Jagalska@biology.leidenuniv.nl RI Schmidt, Thomas/B-6296-2009; OI Schmidt, Thomas/0000-0002-0045-1851; Serge, Arnauld/0000-0003-4271-3706 FU Marie-Curie fellowship; Netherlands Organisation for Scientific Research, Chemical Sciences; American Heart Association, Texas Affiliate [0265158Y] FX We thank P. N. Devreotes and Minghang Zhang for providing us with cAR1-YFP and cm1234-YFP constructs, respectively. This work was supported by the Marie-Curie fellowship (to A. S.), Netherlands Organisation for Scientific Research, Chemical Sciences (to S. K) and by grant 0265158Y from the American Heart Association, Texas Affiliate (to D.H.). NR 50 TC 14 Z9 14 U1 0 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2011 VL 3 IS 6 BP 675 EP 683 DI 10.1039/c0ib00121j PG 9 WC Cell Biology SC Cell Biology GA 773OV UT WOS:000291317500006 PM 21541374 ER PT S AU Thurm, A Bishop, S Shumway, S AF Thurm, Audrey Bishop, Somer Shumway, Stacy BE Matson, JL Sturmey, P TI Developmental Issues and Milestones SO INTERNATIONAL HANDBOOK OF AUTISM AND PERVASIVE DEVELOPMENTAL DISORDERS SE Autism and Child Psychopathology Series LA English DT Article; Book Chapter ID AUTISM SPECTRUM DISORDERS; DIAGNOSTIC OBSERVATION SCHEDULE; FOLLOW-UP; REPETITIVE BEHAVIORS; LANGUAGE-DEVELOPMENT; ASPERGER-SYNDROME; JOINT ATTENTION; 2ND YEAR; AGE 2; SOCIAL COMMUNICATION C1 [Thurm, Audrey; Shumway, Stacy] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. [Bishop, Somer] Cincinnati Childrens Hosp Med Ctr, Kelly OLeary Ctr Autism Spectrum Disorders, Cincinnati, OH 45229 USA. RP Thurm, A (reprint author), NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. EM athurm@mail.nih.gov; somer.bishop@cchmc.org NR 102 TC 2 Z9 2 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2192-922X BN 978-1-4419-8064-9 J9 AUT CHILD PSYCHO PY 2011 BP 159 EP 173 DI 10.1007/978-1-4419-8065-6_10 D2 10.1007/978-1-4419-8065-6 PG 15 WC Psychology, Clinical; Pediatrics SC Psychology; Pediatrics GA BAF66 UT WOS:000304028600010 ER PT B AU Pearson, JL AF Pearson, Jane L. BE OConnor, RC Platt, S Gordon, J TI Challenges in US Suicide Prevention Public Awareness Programmes SO INTERNATIONAL HANDBOOK OF SUICIDE PREVENTION: RESEARCH, POLICY AND PRACTICE LA English DT Article; Book Chapter ID ATTITUDES; BEHAVIOR; IMPACT; ADOLESCENTS; DEPRESSION; PROMOTION; VETERANS; MESSAGES; IDEATION; SEEKING AB Awareness is considered the initial step in suicide prevention efforts in the United States and many nations around the world. Yet there is limited research to guide effective approaches to increasing awareness. A recent review by Dumesnil and Verger (2009) provides a helpful overview of international suicide prevention awareness efforts and called for expert consensus on approaches. An edited book by Hornik (2002) is another comprehensive summary of successful public health communication efforts across the world, with examples of efforts that were more or less successful. Using lessons learned from these reviews, this chapter considers some specific targeted campaign efforts in the United States. Included are efforts aimed at federal and state policy-makers; the news media and entertainment media; and two US demographic groups: high school youth and military veterans. It reviews the goals and intended outcomes for these awareness programmes and highlights opportunities for research for these particular target audiences. Safety issues unique to suicide prevention efforts are considered. With these conclusions in mind, the chapter considers some current research challenges: efficient means of assessing awareness needs in target groups; and how to work with cultural values within target groups, using an example that harnesses new media. C1 NIMH, Suicide Res Consortium, NIH, Bethesda, MD 20892 USA. RP Pearson, JL (reprint author), NIMH, Suicide Res Consortium, NIH, Bethesda, MD 20892 USA. NR 42 TC 3 Z9 3 U1 1 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-99856-3; 978-0-470-68384-2 PY 2011 BP 577 EP 590 D2 10.1002/9781119998556 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BA8ZP UT WOS:000339056800034 ER PT J AU Raiten, DJ Namaste, S Brabin, B AF Raiten, Daniel J. Namaste, Sorrel Brabin, Bernard TI Considerations for the Safe and Effective Use of Iron Interventions in Areas of Malaria Burden - Executive Summary SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE Iron; malaria; children; iron intervention to prevent deficiency; nutrition ID TRANSFERRIN RECEPTOR CONCENTRATIONS; PLASMODIUM-FALCIPARUM-INFECTION; ERYTHROCYTE ZINC PROTOPORPHYRIN; IMMUNODEFICIENCY-VIRUS DISEASE; MEAN CORPUSCULAR VOLUME; DEFICIENCY ANEMIA; SERUM FERRITIN; CHILD UNDERNUTRITION; ALPHA-THALASSEMIA; BETA-THALASSEMIA AB In 2006, the World Health Organization and the United Nations Children's Fund released a joint statement advising that, in regions where the prevalence of malaria and other infectious diseases is high, iron and folic acid supplementation should be limited to those who are identified as iron-deficient. Although precipitated, in large part, by a recent report of adverse events associated with iron supplementation in children, questions about the risk/benefit of iron deficiency and mechanisms underlying potential adverse effects of iron in the context of infection are long-standing. Moreover, the implementation of this revised policy is compromised in most settings by the lack of consensus on the best methods to screen for iron deficiency. In response to these concerns a comprehensive review was conducted by a Technical Working Group (TWG), constituted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the U.S. National Institutes of Health, in partnership with the Bill and Melinda Gates Foundation. The review included an evaluation of the putative mechanisms associated with adverse effects of iron in the context of malaria; applicability of available biomarkers for assessing iron status in the context of infections; and evaluation of evidence with regard to the safety and effectiveness of available interventions to prevent iron deficiency, particularly in areas of endemic malaria. The aim of this paper is to summarize the technical details of the larger TWG review conclusion that the occurrence and mechanism(s) of adverse effects associated with providing iron supplements (i.e., pills/liquid) under conditions of malaria and high infection exposure remain a concern, especially in settings where care and treatment are not readily available or accessible. Iron deficiency remains a problem that demands appropriate clinical care. When target groups have already been identified as being iron-deficient, iron supplementation is the intervention of choice for the treatment of anemia and other manifestations of iron deficiency. Of available intervention options to prevent iron deficiency, supplements are probably least desirable, particularly for infants and children. This paper also provides a synopsis of the TWG responses to the recently published Cochrane Review on the safety of iron supplementation for children in the context of malaria, and a research agenda outlined by the TWG that can best address outstanding questions. C1 [Raiten, Daniel J.; Namaste, Sorrel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Brabin, Bernard] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. RP Raiten, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Room 4B 11, Bethesda, MD 20892 USA. EM raitend@mail.nih.gov NR 72 TC 15 Z9 15 U1 0 U2 4 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD JAN PY 2011 VL 81 IS 1 BP 57 EP 71 DI 10.1024/0300-9831/a000051 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 837ML UT WOS:000296207800007 PM 22002219 ER PT J AU Friedman, DB Laditka, SB Laditka, JN Wu, B Liu, R Price, AE Tseng, W Corwin, SJ Ivey, SL Hunter, R Sharkey, JR AF Friedman, Daniela B. Laditka, Sarah B. Laditka, James N. Wu, Bei Liu, Rui Price, Anna E. Tseng, Winston Corwin, Sara J. Ivey, Susan L. Hunter, Rebecca Sharkey, Joseph R. TI ETHNICALLY DIVERSE OLDER ADULTS' BELIEFS ABOUT STAYING MENTALLY SHARP SO INTERNATIONAL JOURNAL OF AGING & HUMAN DEVELOPMENT LA English DT Article ID PROMOTING COGNITIVE HEALTH; ENGAGED LIFE-STYLE; PHYSICAL-ACTIVITY; UNITED-STATES; SOCIAL INTEGRATION; LEISURE ACTIVITIES; DEMENTIA; DECLINE; POPULATION; IMPAIRMENT AB This study examined diverse older adults' (n = 396, ages 50+) views about how to stay mentally sharp. We conducted 42 focus groups in four languages at nine United States locations using a standardized discussion guide and methods. The groups represented African Americans, American Indians, Chinese Americans, Latinos, Whites other than Latinos, and Vietnamese Americans. All groups mentioned benefits of social interaction. All groups, especially Chinese and African Americans, mentioned benefits of community engagement. Participants in all groups expressed their belief that mental stimulation, particularly reading, promoted cognitive health; African Americans and Whites were especially likely to say that mental exercises (e.g., puzzles) were useful. Results suggest opportunities for education about potential cognitive health benefits of being socially connected through senior center activities and volunteer programs. C1 [Friedman, Daniela B.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Laditka, Sarah B.; Laditka, James N.] Univ N Carolina, Charlotte, NC 28223 USA. [Wu, Bei] Duke Univ, Durham, NC USA. [Liu, Rui] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Price, Anna E.] Sacred Heart Univ, Fairfield, CT USA. [Tseng, Winston; Ivey, Susan L.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Hunter, Rebecca] Univ N Carolina, Chapel Hill, NC USA. [Sharkey, Joseph R.] Texas A&M Hlth Sci Ctr, College Stn, TX USA. RP Friedman, DB (reprint author), Univ S Carolina, Dept Hlth Promot Educ & Behav, 800 Sumter St, Columbia, SC 29208 USA. EM dfriedma@mailbox.sc.edu FU NCCDPHP CDC HHS [1-U48-DP-000054, 1-U48-DP-000025, 1-U48-DP-000059] NR 54 TC 9 Z9 9 U1 3 U2 9 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0091-4150 EI 1541-3535 J9 INT J AGING HUM DEV JI Int. J. Aging Human Dev. PY 2011 VL 73 IS 1 BP 27 EP 52 DI 10.2190/AG.73.1.b PG 26 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 817CV UT WOS:000294649300002 PM 21922798 ER PT J AU Sumita, Y Liu, YN Khalili, S Maria, OM Xia, DS Key, S Cotrim, AP Mezey, E Tran, SD AF Sumita, Yoshinori Liu, Younan Khalili, Saeed Maria, Ola M. Xia, Dengsheng Key, Sharon Cotrim, Ana P. Mezey, Eva Tran, Simon D. TI Bone marrow-derived cells rescue salivary gland function in mice with head and neck irradiation SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Cell therapy; Salivary gland; Head and neck irradiation; Bone marrow; Cell differentiation ID STEM-CELLS; SUBMANDIBULAR-GLAND; EPITHELIAL-CELLS; IN-VIVO; TISSUE; DAMAGE; RADIOTHERAPY; REVERSAL; THERAPY AB Treatment for Most patients with head and neck cancers includes ionizing radiation. A consequence of this treatment is irreversible damage to salivary glands (SGs), which is accompanied by a loss of fluid-secreting acinar-cells and a considerable decrease of saliva output. While there are currently no adequate conventional treatments for this condition, cell-based therapies are receiving increasing attention to regenerate SGs. In this study, we investigated whether bone marrow-derived cells (BMDCs) can differentiate into salivary epithelial cells and restore SG function in head and neck irradiated mice. BMDCs from male mice were transplanted into the tail-vein of 18 Gy-irradiated female mice. Salivary output was increased in mice that received BMDCs transplantation at week 8 and 24 post-irradiation. At 24 weeks after irradiation (IR), harvested SGs (submandibular and parotid glands) of BMDC-treated mice had greater weights than those of non-treated mice. Histological analysis shows that SGs of treated mice demonstrated an increased level of tissue regenerative activity such as blood vessel formation and cell proliferation, while apoptotic activity was increased in non-transplanted mice. The expression of stem cell markers (Sca-1 or c-kit) was detected in BMDC-treated SGs. Finally, we detected an increased ratio of acinar-cell area and approximately 9% of Y-chromosome-positive (donor-derived) salivary epithelial cells in BMDC-treated mice. We propose here that cell therapy using BMDCs can rescue the functional damage of irradiated SGs by direct differentiation of donor BMDCs into salivary epithelial cells. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Sumita, Yoshinori; Liu, Younan; Khalili, Saeed; Maria, Ola M.; Xia, Dengsheng; Tran, Simon D.] McGill Univ, Fac Dentistry, Montreal, PQ H3A 2B2, Canada. [Sumita, Yoshinori] Nagasaki Univ, Grad Sch Biomed Sci, Dept Regenerat Oral Surg, Nagasaki 852, Japan. [Key, Sharon; Cotrim, Ana P.; Mezey, Eva] Natl Inst Dent & Craniofacial Res, Natl Inst Hlth, Bethesda, MD USA. RP Tran, SD (reprint author), McGill Univ, Fac Dentistry, 3640 Univ St,M-43, Montreal, PQ H3A 2B2, Canada. EM simon.tran@mcgill.ca FU Canadian Institutes of Health Research (CIHR); Canada Research Chair FX We wish to thank Dr. Christina K. Haston (McGill University) for her guidance in the fabrication of the lead shield; Dr. R. James Turner (NIDCR/NIH) for donating the NaKC1-cotransporter antibody. We also wish to thank the staff at the McGill University animal facility, the Centre for Bone and Periodontal Research, and the Department of Engineering for technical assistance. This study was supported in part by research funding from the Canadian Institutes of Health Research (CIHR) and the Canada Research Chair. NR 31 TC 49 Z9 57 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD JAN PY 2011 VL 43 IS 1 BP 80 EP 87 DI 10.1016/j.bioce1.2010.09.023 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 712RO UT WOS:000286684100015 PM 20933096 ER PT J AU Bronze-Da-Rocha, E Lin, CM Shimura, T Aladjem, MI AF Bronze-da-Rocha, Elsa Lin, Chii-Mei Shimura, Tsutomu Aladjem, Mirit I. TI Interactions of MCP1 with Components of the Replication Machinery in Mammalian Cells SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE MCP1; DNA replication; pre-replication complex; histone H1; interacting proteins ID ORIGIN RECOGNITION COMPLEX; S-PHASE PROGRESSION; BETA-GLOBIN LOCUS; DNA-REPLICATION; HISTONE H1; HETEROCHROMATIN PROTEIN-1; MOLECULAR-BIOLOGY; CHROMATIN; ASSOCIATION; DYNAMICS AB Eukaryotic DNA replication starts with the assembly of a pre-replication complex (pre-RC) at replication origins. We have previously demonstrated that Metaphase Chromosome Protein 1 (MCP1) is involved in the early events of DNA replication. Here we show that MCP1 associates with proteins that are required for the establishment of the pre-replication complex. Reciprocal immunoprecipitation analysis showed that MCP1 interacted with Cdc6, ORC2, ORC4, MCM2, MCM3 and MCM7, with Cdc45 and PCNA. Immunofluorescence studies demonstrated the co-localization of MCP1 with some of those proteins. Moreover, biochemical studies utilizing chromatin-immunoprecipitation (ChIP) revealed that MCP1 preferentially binds replication initiation sites in human cells. Interestingly, although members of the pre-RC are known to interact with some hallmarks of heterochromatin, our co-immunoprecipitation and immunofluorescence analyses showed that MCP1 did not interact and did not co-localize with heterochromatic proteins including HP1 beta and MetH3K9. These observations suggest that MCP1 is associated with replication factors required for the initiation of DNA replication and binds to the initiation sites in loci that replicate early in S-phase. In addition, immunological assays revealed the association of MCP1 forms with histone H1 variants and mass spectrometry analysis confirmed that MCP1 peptides share common sequences with H1.2 and H1.5 subtypes. C1 [Bronze-da-Rocha, Elsa] Univ Porto, Fac Farm, Lab Bioquim, Dept Ciencias Biol, P-4050047 Oporto, Portugal. [Bronze-da-Rocha, Elsa] Univ Porto, Inst Biol Mol & Celular, P-4050047 Oporto, Portugal. [Shimura, Tsutomu] Tohoku Univ, Inst Dev Aging & Canc, Dept Pathol, Sendai, Miyagi 980, Japan. [Bronze-da-Rocha, Elsa; Lin, Chii-Mei; Shimura, Tsutomu; Aladjem, Mirit I.] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Bronze-Da-Rocha, E (reprint author), Univ Porto, Fac Farm, Lab Bioquim, Dept Ciencias Biol, Rua Anibal Cunha 164, P-4050047 Oporto, Portugal. EM elsa.rocha@ff.up.pt RI REQUIMTE, DTB/M-6204-2013; REQUIMTE, UCIBIO/N-9846-2013; Bronze-da-Rocha, Elsa/K-2723-2013; Aladjem, Mirit/G-2169-2010 OI Bronze-da-Rocha, Elsa/0000-0002-3571-2513; Aladjem, Mirit/0000-0002-1875-3110 FU Luso-American Foundation of Portugal (FLAD); Calouste Gulbenkian Foundation of Portugal; Fulbright Commission of Portugal; NIH, Center for Cancer Research, National Cancer Institute FX We thank Barbara Taylor for expert help in cell sorting and analysis of cell cycle fractions; Sumega Singhania for help in centrifugal elutriation; Dr. Nga Y. Nguyen for the useful advice in mass spectrometry; Dr. Jennifer Seiler for providing the MCM2 antibody; Dr. Paula Almeida Coelho for critical reading and discussion of the manuscript. This work was supported by fellowships from the Luso-American Foundation of Portugal (FLAD), Calouste Gulbenkian Foundation of Portugal and Fulbright Commission of Portugal to Elsa Bronze-da-Rocha, and by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. NR 49 TC 1 Z9 2 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 2 BP 193 EP 208 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 736BH UT WOS:000288464000006 PM 21383955 ER PT J AU Oishi, N Wang, XW AF Oishi, Naoki Wang, Xin Wei TI Novel therapeutic Strategies for Targeting Liver Cancer Stem Cells SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Liver cancer stem cell; Hepatocellular carcinoma; Cholangiocellular carcinoma; Wnt/beta-catenin signaling; TGF-beta signaling; Notch signaling; Hedgehog signaling; BMI-1 signaling; EpCAM; Lin-28; miR-181; Self-renewal; Self-protection ID HUMAN HEPATOCELLULAR-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; WNT SIGNALING PATHWAY; HEPATIC PROGENITOR CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; PHASE-II TRIAL; BETA-CATENIN; FACTOR RECEPTOR; SIDE-POPULATION AB The cancer stem cell (CSC) hypothesis was first proposed over 40 years ago. Advances in CSC isolation were first achieved in hematological malignancies, with the first CSC demonstrated in acute myeloid leukemia. However, using similar strategies and technologies, and taking advantage of available surface markers, CSCs have been more recently demonstrated in a growing range of epithelial and other solid organ malignancies, suggesting that the majority of malignancies are dependent on such a compartment. Primary liver cancer consists predominantly of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). It is believed that hepatic progenitor cells (HPCs) could be the origin of some HCCs and ICCs. Furthermore, stem cell activators such as Wnt/beta-catenin, TGF-beta, Notch and Hedgehog signaling pathways also expedite tumorigenesis, and these pathways could serve as molecular targets to assist in designing cancer prevention strategies. Recent studies indicate that additional factors such as EpCAM, Lin28 or miR-181 may also contribute to HCC progression by targeting HCC CSCs. Various therapeutic drugs that directly modulate CSCs have been examined in vivo and in vitro. However, CSCs clearly have a complex pathogenesis, with a considerable crosstalk and redundancy in signaling pathways, and hence targeting single molecules or pathways may have a limited benefit for treatment. Many of the key signaling molecules are shared by both CSCs and normal stem cells, which add further challenges for designing molecularly targeted strategies specific to CSCs but sparing normal stem cells to avoid side effects. In addition to the direct control of CSCs, many other factors that are needed for the maintenance of CSCs, such as angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance, should be taken into consideration when designing therapeutic strategies for HCC. Here we provide a brief review of molecular signaling in liver CSCs and present insights into new therapeutic strategies for targeting liver CSCs. C1 [Oishi, Naoki; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Center for Cancer Research of the National Cancer Institute [Z01-BC 010313] FX We thank NIH Fellows Editorial Board for editorial assistance of manuscript. This study was supported by grant (Z01-BC 010313) from the Intramural Research Program of the Center for Cancer Research of the National Cancer Institute. NR 221 TC 74 Z9 84 U1 1 U2 26 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 5 BP 517 EP 535 PG 19 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 773LD UT WOS:000291307900003 PM 21552419 ER PT J AU Wang, H Lafdil, F Kong, XN Gao, B AF Wang, Hua Lafdil, Fouad Kong, Xiaoni Gao, Bin TI Signal Transducer and Activator of Transcription 3 in Liver Diseases: A Novel Therapeutic Target SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE STAT3; STAT3 signaling; liver injury; liver diseases ID CELL-MEDIATED HEPATITIS; NF-KAPPA-B; INTESTINAL EPITHELIAL-CELLS; HEPATOCELLULAR-CARCINOMA; STAT3 ACTIVATION; KUPFFER CELLS; NONALCOHOLIC STEATOHEPATITIS; STELLATE CELLS; INTERLEUKIN-6-DEFICIENT MICE; FIBROSIS PROGRESSION AB Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by many cytokines and growth factors and plays a key role in cell survival, proliferation, and differentiation. STAT3 activation is detected virtually in all rodent models of liver injury and in human liver diseases. In this review, we highlight recent advances of STAT3 signaling in liver injury, steatosis, inflammation, regeneration, fibrosis, and hepatocarcinogenesis. The cytokines and small molecules that activate STAT3 in hepatocytes may have therapeutic benefits to treat acute liver injury, fatty liver disease, and alcoholic hepatitis, while blockage of STAT3 may have a therapeutic potential to prevent and treat liver cancer. C1 [Wang, Hua; Kong, Xiaoni; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Lafdil, Fouad] INSERM, U955, Lab Liver Pathophysiol, F-94000 Creteil, France. [Lafdil, Fouad] Univ Paris Est, Fac Med, UMR S955, F-94000 Creteil, France. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU NIAAA, NIH FX The work described here from the authors' laboratory was supported by the intramural program of NIAAA, NIH. NR 151 TC 93 Z9 95 U1 1 U2 17 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 5 BP 536 EP 550 PG 15 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 773LD UT WOS:000291307900004 PM 21552420 ER PT J AU Li, XL Kazgan, N AF Li, Xiaoling Kazgan, Nevzat TI Mammalian Sirtuins and Energy Metabolism SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE sirtuins; energy metabolism; aging; nutrients ID SMALL-MOLECULE ACTIVATORS; PHOSPHATE SYNTHETASE 1; PANCREATIC BETA-CELLS; FATTY-ACID OXIDATION; CALORIE RESTRICTION; LIFE-SPAN; GENE-EXPRESSION; SIR2 HOMOLOG; SACCHAROMYCES-CEREVISIAE; DEACETYLASE ACTIVITY AB Sirtuins are highly conserved NAD(+)-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals to mammalian metabolic homeostasis and stress response. Recent studies have shed light on the critical roles of sirtuins in mammalian energy metabolism in response to nutrient signals. This review focuses on the involvement of two nuclear sirtuins, SIRT1 and SIRT6, and three mitochondrial sirtuins, SIRT3, SIRT4, and SIRT5, in regulation of diverse metabolic processes. C1 [Li, Xiaoling; Kazgan, Nevzat] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Li, XL (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM lix3@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [Z01 ES102205] FX We thank Lawrence J. Forsberg from the UNC-Chapel Hill and members of the Li laboratory for critical reading of the manuscript. The work related to this article was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences to X.L. (Z01 ES102205). NR 126 TC 66 Z9 68 U1 0 U2 13 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 5 BP 575 EP 587 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 773LD UT WOS:000291307900007 PM 21614150 ER PT J AU Zamarron, BF Chen, WJ AF Zamarron, Brian F. Chen, WanJun TI Dual Roles of Immune Cells and Their Factors in Cancer Development and Progression SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE TGF-beta; Tumor Associated Macrophages; Hepatocellular Carcinoma; Treg ID REGULATORY T-CELLS; FAMILIAL ADENOMATOUS POLYPOSIS; TGF-BETA; HEPATOCELLULAR-CARCINOMA; SUPPRESSOR-CELLS; INNATE IMMUNITY; HEPATITIS-B; INFLAMMATION; GROWTH; MICE AB Traditional wisdom holds that intact immune responses, such as immune surveillance or immunoediting, are required for preventing and inhibiting tumor development; but recent evidence has also indicated that unresolved immune responses, such as chronic inflammation, can promote the growth and progression of cancer. Within the immune system, cytotoxic CD8(+) and CD4(+) Th1 T cells, along with their characteristically produced cytokine IFN-gamma, function as the major anti-tumor immune effector cells, whereas tumor associated macrophages (TAM) or myeloid-derived suppressive cells (MDSC) and their derived cytokines IL-6, TNF, IL-1 beta and IL-23 are generally recognized as dominant tumor-promoting forces. However, the roles played by Th17 cells, CD4(+) CD25(+) Foxp3(+) regulatory T lymphocytes and immunoregulatory cytokines such as TGF-beta in tumor development and survival remain elusive. These immune cells and the cellular factors produced from them, including both immunosuppressive and inflammatory cytokines, play dual roles in promoting or discouraging cancer development, and their ultimate role in cancer progression may rely heavily on the tumor microenvironment and the events leading to initial propagation of carcinogenesis. C1 [Zamarron, Brian F.; Chen, WanJun] Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Chen, WJ (reprint author), Natl Inst Dent & Craniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM wchen@dir.nidcr.nih.gov OI Zamarron, Brian/0000-0001-6549-4230 FU NIH, NIDCR FX We thank Drs. Joanne Konkel and Takashi Maruyama, OIIB, NIDCR, NIH for critically reading this manuscript. This research was supported by the Intramural Research Program of the NIH, NIDCR. NR 47 TC 172 Z9 187 U1 1 U2 22 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 5 BP 651 EP 658 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 773LD UT WOS:000291307900014 PM 21647333 ER PT J AU Xue, L Yi, H Huang, Z Shi, YB Li, WX AF Xue, Lu Yi, Hong Huang, Zan Shi, Yun-Bo Li, Wen-Xin TI Global Gene Expression during the Human Organogenesis: From Transcription Profiles to Function Predictions SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Review DE Human embryonic development; Gene expression profile; Gene regulation database; Organogenesis; Microarrays; Maternal genes ID EMBRYONIC STEM-CELLS; PREIMPLANTATION MOUSE EMBRYO; SIGNALING PATHWAYS; CDNA MICROARRAY; HUMAN OOCYTES; GENOME-WIDE; BLASTOCYST; GASTRULATION; ACTIVATION; SIGNATURE AB Human embryogenesis includes an integrated set of complex yet coordinated development of different organs and tissues, which is regulated by the spatiotemporal expression of many genes. Deciphering the gene regulation profile is essential for understanding the molecular basis of human embryo development. While molecular and genetic studies in mouse have served as a valuable tool to understand mammalian development, significant differences exists in human and mouse development at morphological and genomic levels. Thus it is important to carry out research directly on human embryonic development. Here we will review some recent studies on gene regulation during human embryogenesis with particular focus on the period of organogenesis, which had not been well studied previously. We will highlight a gene expression database of human embryos from the 4(th) to the 9(th) week. The analysis of gene regulation during this period reveals that genes functioning in a given developmental process tend to be coordinately regulated during human embryogenesis. This feature allows us to use this database to identify new genes important for a particular developmental process/pathway and deduce the potential function of a novel gene during organogenesis. Such a gene expression atlas should serve as an important resource for molecular study of human development and pathogenesis. C1 [Xue, Lu; Yi, Hong; Huang, Zan; Li, Wen-Xin] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China. [Xue, Lu] South Cent Univ Nationalities, Coll Life Sci, Wuhan 430074, Peoples R China. [Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Li, WX (reprint author), Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China. EM shi@helix.nih.gov; liwxlab@whu.edu.cn FU National High Technology Research and Development Program of China (863 Program) [2006AA02A306]; National Natural Science Foundation of China [30900265, 31101047]; NICHD, National Institutes of Health FX This work was supported by National High Technology Research and Development Program of China (863 Program) Grant 2006AA02A306, National Natural Science Foundation of China Grant 30900265 and 31101047). Y.-B. Shi was supported by NICHD Intramural Research Program, National Institutes of Health. NR 41 TC 5 Z9 5 U1 0 U2 3 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 7 BP 1068 EP 1076 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 861HK UT WOS:000298009800015 PM 21927576 ER PT J AU Massimelli, MJ Kang, JG Majerciak, V Le, SY Liewehr, DJ Steinberg, SM Zheng, ZM AF Massimelli, Maria J. Kang, Jeong-Gu Majerciak, Vladimir Le, Shu-Yun Liewehr, David J. Steinberg, Seth M. Zheng, Zhi-Ming TI Stability of a Long Noncoding Viral RNA Depends on a 9-nt Core Element at the RNA 5 ' End to Interact with Viral ORF57 and Cellular PABPC1 SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE KSHV; long non-coding RNA; ORF57; PAN; RNA stability; RNA accumulation; PABPC1; E1B-AP5 ID SARCOMA-ASSOCIATED HERPESVIRUS; POLYADENYLATED NUCLEAR-RNA; PRE-MESSENGER-RNA; KAPOSIS-SARCOMA; GENE-EXPRESSION; DNA-SEQUENCES; ENDOTHELIAL-CELLS; KSHV INFECTION; PROTEIN; HUMAN-HERPESVIRUS-8 AB Kaposi sarcoma-associated herpesvirus (KSHV) ORF57, also known as Mta (mRNA transcript accumulation), enhances viral intron-less transcript accumulation and promotes splicing of intron-containing viral RNA transcripts. In this study, we identified KSHV PAN, a long non-coding polyadenylated nuclear RNA as a main target of ORF57 by a genome-wide CLIP (cross-linking and immunoprecipitation) approach. KSHV genome lacking ORF57 expresses only a minimal amount of PAN. In cotransfection experiments, ORF57 alone increased PAN expression by 20-30-fold when compared to vector control. This accumulation function of ORF57 was dependent on a structured RNA element in the 5' PAN, named MRE (Mta responsive element), but not much so on an ENE (expression and nuclear retention element) in the 3' PAN previously reported by other studies. We showed that the major function of the 5' PAN MRE is increasing the RNA half-life of PAN in the presence of ORF57. Further mutational analyses revealed a core motif consisting of 9 nucleotides in the MRE-II, which is responsible for ORF57 interaction and function. The 9-nt core in the MRE-II also binds cellular PABPC1, but not the E1B-AP5 which binds another region of the MRE-II. In addition, we found that PAN RNA is partially exportable in the presence of ORF57. Together, our data provide compelling evidence as to how ORF57 functions to accumulate a non-coding viral RNA in the course of virus lytic infection. C1 [Massimelli, Maria J.; Kang, Jeong-Gu; Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. [Le, Shu-Yun] NCI, Nanobiol Program, NIH, Bethesda, MD 20892 USA. [Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, NIH, 10 Ctr Dr,Rm 6N106, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU NCI, Center for Cancer Research, National Institutes of Health FX This work was supported by the Intramural Research Program of the NCI, Center for Cancer Research, National Institutes of Health. We thank Dr. Michael Kruhlak for his critical reading of this manuscript, Dr. Jae Jung for providing doxycycline-inducible TREx BCBL1-Rta and -vector cell lines, Yan Yuan for KSHV ORF50 expression vector, Myriam Gorospe, Joan Steitz, and other members of the Zheng laboratory for their assistance and critical comments in the course of this study. NR 58 TC 30 Z9 30 U1 1 U2 7 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 8 BP 1145 EP 1160 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 861HQ UT WOS:000298010400006 PM 22043172 ER PT J AU Elizondo, G Rodriguez-Sosa, M Estrada-Muniz, E Gonzalez, FJ Vega, L AF Elizondo, Guillermo Rodriguez-Sosa, Miriam Estrada-Muniz, Elizabet Gonzalez, Frank J. Vega, Libia TI Deletion of the Aryl Hydrocarbon Receptor Enhances the Inflammatory Response to Leishmania major Infection SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Aryl hydrocarbon receptor; Inflammatory response; Regulatory T cells; Leishmania major ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INTERFERON-GAMMA-PRODUCTION; AHR-NULL MICE; FACTOR-ALPHA; TNF-ALPHA; CELL-PROLIFERATION; DEFICIENT MICE; LIPOXIN A(4); IL-10 AB The aryl hydrocarbon receptor (AhR) is a ligand-activated receptor that mediates the toxicity of environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recently, it has been shown that the AhR plays a role in immune and inflammatory regulation. However, most of these studies are based on the activation of AhR by exogenous ligands. Therefore, in the present study, we addressed the role of this transcription factor, in the absent of exogenous ligand, on the immune response to Leishmania major infection. Our results indicate that inactivation of the AhR results in an alteration of the levels of several cytokines. Lymph node cells from infected Ahr-null animals displayed an increase in IFN gamma and IL-12 levels, together with a decrease in IL-4 and IL-10 levels compared to wild-type (wt) mice. Ahr-null mice also presented higher serum levels of the pro-inflammatory cytokine TNF-alpha prior to parasite inoculation and during infection compared to wt mice. Moreover, a 30% decrease in the population of T(reg) cells was observed in Ahr-null mice. This decrease was associated with a reduction in Foxp3 mRNA levels. Finally, the alteration in the cytokine profile results in a better resolution of the L. major infection. C1 [Estrada-Muniz, Elizabet; Vega, Libia] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Toxicol, Mexico City 07360, DF, Mexico. [Elizondo, Guillermo] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Biol Celular, Mexico City 07360, DF, Mexico. [Rodriguez-Sosa, Miriam] UNAM, Fac Estudios Super Iztacala, Unidad Biomed, Tlalnepantla 54090, Estado De Mexic, Mexico. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Vega, L (reprint author), Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Dept Toxicol, Av IPN 2508 San Pedro Zacatenco, Mexico City 07360, DF, Mexico. EM lvega@cinvestav.mx RI Vega, Libia/C-3391-2013 OI Vega, Libia/0000-0002-4993-5267 NR 41 TC 12 Z9 12 U1 1 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2011 VL 7 IS 9 BP 1220 EP 1229 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 861HW UT WOS:000298011000002 PM 22110376 ER PT J AU Li, R Zhao, Y Fan, WW Chen, HY Chen, YY Liu, YH Chen, G Zhou, KK Huang, FP Mao, Y Zhou, LF Lu, D Shugart, YY AF Li, Rui Zhao, Yao Fan, Weiwei Chen, Hongyan Chen, Yuanyuan Liu, Yanhong Chen, Gong Zhou, Keke Huang, Fengping Mao, Ying Zhou, Liangfu Lu, Daru Shugart, Yin Yao TI Possible association between polymorphisms of human vascular endothelial growth factor A gene and susceptibility to glioma in a Chinese population SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE VEGFA; angiogenesis; glioma; polymorphism; cumulative effect ID BREAST-CANCER RISK; VEGF GENE; DIABETIC-RETINOPATHY; TUMOR ANGIOGENESIS; FACTOR EXPRESSION; IN-VIVO; GRADE; SURVIVAL; SNPS; IDENTIFICATION AB Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single-nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer-free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single-locus analysis, we found that rs2010963 (G+405C, G-634C) [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.04-1.58; GC/CC vs. GG] and rs3025030 (OR = 2.21; 95% CI = 1.18-4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR = 0.66; 95% CI = 0.47-0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype-based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20-40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p = 0.002, p(corrected) = 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38-fold for each additional adverse genotype he or she carries (p(trend) = 8.4 x 10(-5)). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation. C1 [Li, Rui; Fan, Weiwei; Chen, Hongyan; Chen, Yuanyuan; Liu, Yanhong; Lu, Daru] Fudan Univ, State Key Lab Genet Engn, Ctr Fudan VARI Genet Epidemiol, Sch Life Sci, Shanghai 200433, Peoples R China. [Li, Rui; Fan, Weiwei; Chen, Hongyan; Chen, Yuanyuan; Liu, Yanhong; Lu, Daru] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 200433, Peoples R China. [Zhao, Yao; Chen, Gong; Zhou, Keke; Huang, Fengping; Mao, Ying; Zhou, Liangfu] Fudan Univ, Huashan Hosp, Dept Neurosurg, Shanghai 200433, Peoples R China. [Liu, Yanhong] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Shugart, Yin Yao] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Shugart, Yin Yao] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. RP Lu, D (reprint author), Fudan Univ, State Key Lab Genet Engn, Ctr Fudan VARI Genet Epidemiol, Sch Life Sci, 220 Handan Rd, Shanghai 200433, Peoples R China. EM yingmao168@hotmail.com; drlu@fudan.edu.cn FU Shanghai Science and Technology Research Program [09JC1402200]; Natural Science Foundation of China [30800622]; Shanghai Subject Chief Scientist for Public Health [08GWD07] FX Grant sponsor: Shanghai Science and Technology Research Program; Grant number: 09JC1402200; Grant sponsor: Natural Science Foundation of China; Grant number: 30800622; Grant sponsor: Shanghai Subject Chief Scientist for Public Health; Grant number: 08GWD07 NR 47 TC 13 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 1 PY 2011 VL 128 IS 1 BP 166 EP 175 DI 10.1002/ijc.25306 PG 10 WC Oncology SC Oncology GA 680CJ UT WOS:000284209700017 PM 20209496 ER PT J AU Stillman, AE Oudkerk, M Bluemke, D Bremerich, J Esteves, FP Garcia, EV Gutberlet, M Hundley, WG Jerosch-Herold, M Kuijpers, D Kwong, RK Nagel, E Lerakis, S Oshinski, J Paul, JF Underwood, R Wintersperger, BJ Rees, MR AF Stillman, Arthur E. Oudkerk, Matthijs Bluemke, David Bremerich, Jens Esteves, Fabio P. Garcia, Ernest V. Gutberlet, Matthias Hundley, W. Gregory Jerosch-Herold, Michael Kuijpers, Dirkjan Kwong, Raymond K. Nagel, Eike Lerakis, Stamatios Oshinski, John Paul, Jean-Francois Underwood, Richard Wintersperger, Bernd J. Rees, Michael R. TI Assessment of acute myocardial infarction: current status and recommendations from the North American society for cardiovascular imaging and the European society of cardiac radiology SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Review DE Acute myocardial infarction; Acute coronary syndrome; Cardiac imaging ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; ST-SEGMENT-ELEVATION; PERCUTANEOUS CORONARY INTERVENTION; ENHANCED MAGNETIC-RESONANCE; DOSE DOBUTAMINE ECHOCARDIOGRAPHY; DELAYED CONTRAST ENHANCEMENT; ACUTE CHEST-PAIN; STRESS ECHOCARDIOGRAPHY; EMERGENCY-DEPARTMENT; MICROVASCULAR OBSTRUCTION AB There are a number of imaging tests that are used in the setting of acute myocardial infarction and acute coronary syndrome. Each has their strengths and limitations. Experts from the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging together with other prominent imagers reviewed the literature. It is clear that there is a definite role for imaging in these patients. While comparative accuracy, convenience and cost have largely guided test decisions in the past, the introduction of newer tests is being held to a higher standard which compares patient outcomes. Multicenter randomized comparative effectiveness trials with outcome measures are required. C1 [Stillman, Arthur E.; Esteves, Fabio P.; Garcia, Ernest V.; Lerakis, Stamatios; Oshinski, John] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. [Oudkerk, Matthijs; Kuijpers, Dirkjan] Univ Groningen Hosp, Dept Radiol, Groningen, Netherlands. [Bluemke, David] Natl Inst Biomed Imaging & Biomed Engn, NIH Clin Ctr, Bethesda, MD USA. [Bremerich, Jens] Univ Basel Hosp, Dept Radiol, CH-4031 Basel, Switzerland. [Gutberlet, Matthias] Univ Leipzig, Dept Diagnost & Intervent Radiol, Ctr Heart, Leipzig, Germany. [Hundley, W. Gregory] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Cardiol & Radiol, Winston Salem, NC 27103 USA. [Jerosch-Herold, Michael] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Kwong, Raymond K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA USA. [Nagel, Eike] St Thomas Hosp, Kings Coll London, BHF Ctr Res Excellence, NIHR Biomed Res Ctr,Div Imaging Sci, London, England. [Lerakis, Stamatios] Emory Univ, Dept Cardiol, Atlanta, GA 30322 USA. [Paul, Jean-Francois] Ctr Chirurg Marie Lannelongue, Dept Radiol, Le Plessis Robinson, France. [Underwood, Richard] Royal Brompton Hosp, Imperial Coll London, London SW3 6LY, England. [Wintersperger, Bernd J.] Univ Munich, Univ Hosp Grosshadern, Dept Clin Radiol, Munich, Germany. [Rees, Michael R.] Bristol Royal Infirm & Gen Hosp, Dept Radiol, Bristol, Avon, England. RP Stillman, AE (reprint author), Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. EM aestill@emory.edu RI Library, Woodruff Health/A-6096-2012; Nagel, Eike/C-6903-2008; OI Nagel, Eike/0000-0002-6044-950X; Bremerich, Jens/0000-0002-1002-8483; Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [ZIA CL090019-01, ZIA EB000072-01] NR 126 TC 18 Z9 19 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD JAN PY 2011 VL 27 IS 1 BP 7 EP 24 DI 10.1007/s10554-010-9714-0 PG 18 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 718RF UT WOS:000287142900003 PM 20972835 ER PT J AU Nelson, SJ Zeng, K Kilbourne, J AF Nelson, Stuart J. Zeng, Kelly Kilbourne, John TI Building a standards-based and collaborative e-prescribing tool: MyRxPad SO INTERNATIONAL JOURNAL OF DATA MINING AND BIOINFORMATICS LA English DT Article DE RxNorm; e-prescribing; MyRxPad; CCD; continuity of care document; PHR; personal health record ID ORDER ENTRY AB MyRxPad (rxp.nlm.nih.gov) is a prototype application intended to enable a practitioner patient collaborative approach towards e-prescribing: patients play an active role by maintaining up-to-date and accurate medication lists. Prescribers make well-informed and safe prescribing decisions based on personal medication records contributed by patients. MyRxPad is thus the vehicle for collaborations with patients using MyMedicationList (MML). Integration with personal medication records in the context of e-prescribing is thus enabled. We present our experience in applying RxNorm in an c-prescribing setting: using standard names and codes to capture prescribed medication as well as extracting information from RxNorm to support medication-related clinical decision. C1 [Nelson, Stuart J.; Zeng, Kelly; Kilbourne, John] NIH, US Natl Lib Med, Bethesda, MD 20892 USA. RP Nelson, SJ (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM nelson@nlm.nih.gov; zeng@nlm.nih.gov; kilbourj@nlm.nih.gov NR 21 TC 1 Z9 1 U1 0 U2 0 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 896, CH-1215 GENEVA, SWITZERLAND SN 1748-5673 J9 INT J DATA MIN BIOIN JI Int. J. Data Min. Bioinform. PY 2011 VL 5 IS 3 SI SI BP 252 EP 265 PG 14 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 788CN UT WOS:000292423100003 PM 21805822 ER PT J AU Loi, M Di Paolo, D Becherini, P Zorzoli, A Perri, P Carosio, R Cilli, M Ribatti, D Brignole, C Pagnan, G Ponzoni, M Pastorino, F AF Loi, Monica Di Paolo, Daniela Becherini, Pamela Zorzoli, Alessia Perri, Patrizia Carosio, Roberta Cilli, Michele Ribatti, Domenico Brignole, Chiara Pagnan, Gabriella Ponzoni, Mirco Pastorino, Fabio TI The use of the orthotopic model to validate antivascular therapies for cancer SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE orthotopic model; vascular disrupting agent; antivascular therapy; cancer ID TUMOR BLOOD-VESSELS; VASCULAR DISRUPTING AGENTS; MICROVASCULAR CASTING TECHNIQUE; COMBRETASTATIN A-4 PHOSPHATE; BINDS ANIONIC PHOSPHOLIPIDS; NECROSIS-FACTOR-ALPHA; SOLID TUMORS; NUDE-MICE; IN-VIVO; ENDOTHELIAL-CELLS AB The orthotopic model reproduces aspects of the tumour microenvironment and emulates a number of important biological features of cancer progression, angiogenesis, metastasis and resistance. Due to its parallels with human cancer, the model can be used to evaluate therapeutic responses to various therapies. This review outlines the importance of using the orthotopic implantation of tumour cells in mice models for evaluating the effectiveness of antivascular therapies. C1 [Loi, Monica; Di Paolo, Daniela; Becherini, Pamela; Zorzoli, Alessia; Perri, Patrizia; Carosio, Roberta; Brignole, Chiara; Pagnan, Gabriella; Ponzoni, Mirco; Pastorino, Fabio] G Gaslini Childrens Hosp, Expt Therapies Unit, Lab Oncol, I-16148 Genoa, Italy. [Cilli, Michele] Natl Canc Inst, Anim Res Facil, Genoa, Italy. [Ribatti, Domenico] Univ Bari, Dept Human Anat & Histol, I-70121 Bari, Italy. RP Ponzoni, M (reprint author), G Gaslini Childrens Hosp, Expt Therapies Unit, Lab Oncol, I-16148 Genoa, Italy. EM mircoponzoni@ospedale-gaslini.ge.it; fabiopastorino@ospedale-gaslini.ge.it RI Di Paolo, Daniela/J-7681-2016; Ponzoni, Mirco/J-7713-2016 OI Di Paolo, Daniela/0000-0001-7264-6888; Ponzoni, Mirco/0000-0002-6164-4286 FU Associazione Italiana Ricerca Cancro (IG and MFAG), Italian Ministry of Health FX We thank Ambrilia Biopharma Inc for providing us with TVT-DOX. Work supported by Associazione Italiana Ricerca Cancro (IG and MFAG), Italian Ministry of Health. NR 129 TC 20 Z9 20 U1 0 U2 2 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2011 VL 55 IS 4-5 SI SI BP 547 EP 555 DI 10.1387/ijdb.103230ml PG 9 WC Developmental Biology SC Developmental Biology GA 831RH UT WOS:000295748300024 PM 21858775 ER PT J AU O'Brien, J Hansen, K Barkan, D Green, J Schedin, P AF O'Brien, Jenean Hansen, Kirk Barkan, Dalit Green, Jeffrey Schedin, Pepper TI Non-steroidal anti-inflammatory drugs target the pro-tumorigenic extracellular matrix of the postpartum mammary gland SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE NSAID; breast cancer; involution; tenascin-C; proteomic; 3D culture ID BASEMENT-MEMBRANE CULTURES; BREAST-CANCER; TENASCIN-C; REPRODUCTIVE STATE; EPITHELIAL-CELLS; GENE-EXPRESSION; COLLAGEN; ASPIRIN; PROGRESSION; FIBRONECTIN AB Breast cancer patients diagnosed postpartum have poor prognosis. The postpartum mammary gland undergoes tissue regression to return to the pre-pregnant state. This involution is characterized by wound healing programs known to be tumor promotional in other contexts. Previous studies have shown that mammary extracellular matrix (ECM) from nulliparous rats has tumor suppressive attributes, while mammary ECM from involuting mammary glands is promotional. In models of pregnancy-associated breast cancer, non-steroidal anti-inflammatory drug (NSAID) treatment targeted to postpartum involution inhibits tumor progression, in part by suppressing COX-2 dependent collagen deposition. Because mammary ECM proteins are coordinately regulated, NSAID treatment is anticipated to result in additional protective changes in the mammary extracellular matrix. Here, systemic NSAID treatment was utilized during postpartum involution to reduce mammary COX-2 activity. ECM was isolated from actively involuting glands of rats treated with NSAIDs and compared to ECM isolated from control-involution and nulliparous rats in 3D cell culture and xenograft assays. Compositional changes in ECM between groups were identified by proteomics. In four distinct 3D culture assays, normal and transformed mammary epithelial cells plated in NSAID-involution ECM, phenocopied cells plated in ECM from nulliparous rats rather than ECM from control-involution rats. Tumor cells mixed with NSAID-involution ECM and injected orthotopically in mice formed smaller tumors than cells mixed with control-involution ECM. Proteomic analyses identified and 3D culture assays implicated the ECM protein tenascin-C as a potential mediator of tumor progression during involution that is decreased by NSAID treatment. In summary, NSAID treatment decreases tumor-promotional attributes of postpartum involution mammary ECM. C1 [O'Brien, Jenean; Schedin, Pepper] Univ Colorado Anschutz Med Campus, Div Med Oncol, Sch Med, Aurora, CO 80045 USA. [O'Brien, Jenean; Schedin, Pepper] Univ Colorado Anschutz Med Campus, Program Canc Biol, Aurora, CO USA. [Hansen, Kirk] Univ Colorado Anschutz Med Campus, Dept Biochem & Mol Genet, Sch Med, Aurora, CO USA. [Barkan, Dalit] Univ Haifa, Fac Nat Sci, Dept Biol, IL-31999 Haifa, Israel. [Green, Jeffrey] NIH, Transgen Oncogenesis & Genom Sect, Lab Cell Biol & Genet, Bethesda, MD USA. [Schedin, Pepper] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Schedin, Pepper] AMC Canc Res Ctr, Denver, CO USA. RP Schedin, P (reprint author), Univ Colorado Anschutz Med Campus, Div Med Oncol, Sch Med, 12801 E 17th Ave, Aurora, CO 80045 USA. EM pepper.schedin@ucdenver.edu FU DOD [BC060531, BC073482]; Komen Foundation [KG090629]; Mary Kay Ash Foundation [078-08]; NIH NCRR [S10RR023015, CA132741]; Center for Cancer Research, National Cancer Institute, NIH FX Supported by DOD Synergistic Idea Award #BC060531, Komen Foundation #KG090629, and Mary Kay Ash Foundation #078-08 to PS, NIH NCRR #S10RR023015 and R21 #CA132741 to KH and DOD Predoctoral Grant #BC073482 to JO. This work was supported in part by the Intramural Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 58 TC 19 Z9 19 U1 0 U2 4 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2011 VL 55 IS 7-9 SI SI BP 745 EP 755 DI 10.1387/ijdb.113379jo PG 11 WC Developmental Biology SC Developmental Biology GA 883ST UT WOS:000299655900009 PM 22161831 ER PT J AU Negussie, AH Yarmolenko, PS Partanen, A Ranjan, A Jacobs, G Woods, D Bryant, H Thomasson, D Dewhirst, MW Wood, BJ Dreher, MR AF Negussie, Ayele H. Yarmolenko, Pavel S. Partanen, Ari Ranjan, Ashish Jacobs, Genevieve Woods, David Bryant, Henry Thomasson, David Dewhirst, Mark W. Wood, Bradford J. Dreher, Matthew R. TI Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE doxorubicin (Adriamycin); heat targeted drug delivery (nanoparticles, liposomes); high intensity focused ultrasound; MR imaging; imageable temperature sensitive liposomes ID LARGE UNILAMELLAR VESICLES; DRUG-DELIVERY SYSTEMS; IN-VIVO; MACROMOLECULAR THERAPEUTICS; THERMOSENSITIVE LIPOSOMES; PARAMAGNETIC LIPOSOMES; TARGETED DELIVERY; CONTRAST AGENTS; PH GRADIENT; RELEASE AB Methods: iLTSL was passively loaded with Gd-HP-DO3A and actively loaded with doxorubicin. Doxorubicin and Gd-HP-DO3A release was quantified by fluorescence and spectroscopic techniques, respectively. Release with MR-HIFU was examined in tissue-mimicking phantoms containing iLTSL and in a VX2 rabbit tumour model. Results: iLTSL demonstrated consistent size and doxorubicin release kinetics after storage at 4 degrees A degrees C for 7 days. Release of doxorubicin and Gd-HP-DO3A from iLTSL was minimal at 37 degrees A degrees C but fast when heated to 41.3 degrees A degrees C. The magnitude of release was not significantly different between doxorubicin and Gd-HP-DO3A over 10 min in HEPES buffer and plasma at 37 degrees A degrees, 40 degrees A degrees and 41.3 degrees A degrees C (p > 0.05). Relaxivity of iLTSL increased significantly (p < 0.0001) from 1.95 +/-+/- 0.05 to 4.01 +/-+/- 0.1 mMs59 NR 65 TC 15 Z9 15 U1 1 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2011 VL 6 BP 2907 EP 2923 DI 10.2147/IJN.S23724 PG 17 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 857BH UT WOS:000297688400001 PM 22131836 ER PT J AU Willis, G AF Willis, Gordon TI Using Mixed Methods to Evaluate Multi-Cultural Survey Questionnaires SO INTERNATIONAL JOURNAL OF QUALITATIVE METHODS LA English DT Meeting Abstract C1 [Willis, Gordon] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV ALBERTA, INT INST QUALITATIVE METHODOLOGY PI EDMONTON PA 5-217, EDMONTON CLINIC HEALTH ACAD, 11405 87 AVENUE, EDMONTON, AB T6G 1C9, CANADA SN 1609-4069 J9 INT J QUAL METH JI Int. J. Qual. Meth. PY 2011 VL 10 IS 4 BP 521 EP 521 PG 1 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 059ZL UT WOS:000312744200130 ER PT J AU Julian, TB Costantino, JP Vicini, FA White, JR Winter, KA Anhui, DW Kuske, RR Rabinovitch, R Curran, WJ Wolmark, N AF Julian, T. B. Costantino, J. P. Vicini, F. A. White, J. R. Winter, K. A. Anhui, D. W. Kuske, R. R. Rabinovitch, R. Curran, W. J., Jr. Wolmark, N. TI Early Toxicity Results with 3-D Conformal External Beam Therapy (CEBT) from the NSABP B-39/RTOG 0413 Accelerated Partial Breast Irradiation (APBI) Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract C1 [Julian, T. B.] Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA. [Julian, T. B.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Costantino, J. P.] NSABP, Pittsburgh, PA USA. [Costantino, J. P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Vicini, F. A.] NSABP William Beaumont Hosp, Royal Oak, MN USA. [White, J. R.] Med Coll Wisconsin, RTOG, Milwaukee, WI 53226 USA. [Winter, K. A.] RTOG, Philadelphia, PA USA. [Anhui, D. W.] Virginia Commonwealth Univ, NSABP, Richmond, VA USA. [Kuske, R. R.] Arizona Breast Canc Specialists, NSABP, Scottsdale, AZ USA. [Rabinovitch, R.] Univ Colorado Hosp, RTOG, Aurora, CO USA. [Curran, W. J., Jr.] RTOG Emory Univ, Atlanta, GA USA. [Wolmark, N.] NSABP Allegheny Gen Hosp, Pittsburgh, PA USA. NR 0 TC 19 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2011 VL 81 IS 2 SU S BP S7 EP S7 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 840AX UT WOS:000296411700013 ER PT S AU Fujimoto, M Hayashi, T AF Fujimoto, Michiko Hayashi, Teruo BE Jeon, KW TI NEW INSIGHTS INTO THE ROLE OF MITOCHONDRIA-ASSOCIATED ENDOPLASMIC RETICULUM MEMBRANE SO INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY, VOL 292 SE International Review of Cell and Molecular Biology LA English DT Review; Book Chapter DE Endoplasmic reticulum; Mitochondria; MAM; Mitochondria-associated membrane; Calcium signaling; Phospholipids; Apoptosis ID RAT-LIVER MITOCHONDRIA; CALCIUM SIGNAL TRANSMISSION; PERMEABILIZED ANIMAL-CELLS; PANCREATIC BETA-CELL; HAMSTER OVARY CELLS; ALZHEIMERS-DISEASE; SIGMA-1 RECEPTORS; MAMMALIAN-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; SARCOPLASMIC-RETICULUM AB The mitochondria-associated endoplasmic reticulum membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) membrane that regulates ER mitochondria communications. The MAM is characterized by direct apposition to a mitochondrion, a unique lipid profile, and the expression of a unique set of proteins involved in Ca2+ signaling, phospholipid biosynthesis, protein folding, and membrane tethering. The association of the MAM with a mitochondrion is in part cytoskeleton independent and dynamically changed by an elevation of the cytosolic Ca2+ level. The mechanisms underlying the genesis of MAM are unclear but might involve COPI-dependent vesicular transport and soluble NSF attachment protein receptor. The MAM is recognized as a center for intermembrane transport of phospholipids and for direct Ca2+ transmission to mitochondria that activates the tricarboxylic acid cycle. However, MAM might be also involved in the interorganelle transport of cholesterol, ceramides, ATP, and proteins as well as in proteasomal protein degradation and lipid droplet formation. Recent studies have begun to unveil the importance of interorganelle communication in the innate immune response to virus infection and in the pathophysiology of neurodegenerative/neurodevelopmental disorders. Thus, drug discovery aimed at regulating ER-to-mitochondria communication may open a new avenue in treatments of human diseases. C1 [Fujimoto, Michiko; Hayashi, Teruo] Natl Inst Drug Abuse, Cellular Stress Signaling Unit, Cellular Pathobiol Sect,DHHS, Integrat Neurosci Branch,Intramural Res Program,N, Baltimore, MD USA. RP Fujimoto, M (reprint author), Natl Inst Drug Abuse, Cellular Stress Signaling Unit, Cellular Pathobiol Sect,DHHS, Integrat Neurosci Branch,Intramural Res Program,N, Baltimore, MD USA. FU Intramural NIH HHS NR 244 TC 35 Z9 35 U1 4 U2 21 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1937-6448 BN 978-0-12-386033-0 J9 INT REV CEL MOL BIO JI Int. Rev. Cell Mol. Biol. PY 2011 VL 292 BP 73 EP 117 DI 10.1016/B978-0-12-386033-0.00002-5 PG 45 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BYN13 UT WOS:000299397600002 PM 22078959 ER PT S AU Lee, NR Lopez, KC Adeyemi, EI Giedd, JN AF Lee, Nancy Raitano Lopez, Katherine C. Adeyemi, Elizabeth I. Giedd, Jay N. BE Fidler, DJ TI SEX CHROMOSOME ANEUPLOIDIES: A WINDOW FOR EXAMINING THE EFFECTS OF THE X AND Y CHROMOSOMES ON SPEECH, LANGUAGE, AND SOCIAL DEVELOPMENT SO INTERNATIONAL REVIEW OF RESEARCH IN DEVELOPMENTAL DISABILITIES: EARLY DEVELOPMENT IN NEUROGENETIC DISORDERS, VOL 40 SE International Review of Research in Developmental Disabilities LA English DT Article; Book Chapter ID LINKED GENE-EXPRESSION; TURNER-SYNDROME; KLINEFELTER-SYNDROME; RECOGNITION DEFICITS; MENTAL-RETARDATION; GENDER DIFFERENCES; BRAIN-DEVELOPMENT; BEHAVIOR PROBLEMS; AUTISM-SPECTRUM; META-ANALYSIS AB In this chapter, the existing literature on speech, language, and social development in children with sex chromosome aneuploidies (SCAs) is reviewed. Given the scarcity of studies of young children with SCAs, the topic of this volume, studies of children of all ages as well as some studies of adults are summarized in order to begin to describe the developmental unfolding of the speech, language, and social phenotypes associated with these conditions. A particular emphasis is placed on (a) hypothesized dosage effects of differing numbers of X and Y chromosomes on these phenotypes, and (b) the importance of examining both speech/language and social development in concert, given the close and bidirectional relations between these domains of functioning in typical and atypical development. C1 [Lee, Nancy Raitano; Lopez, Katherine C.; Adeyemi, Elizabeth I.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Lee, NR (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713 NR 114 TC 3 Z9 3 U1 2 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 2211-6095 BN 978-0-12-374478-4 J9 INT REV RES DEV DISA JI Int. Rev. Res. Dev. Disabil. PY 2011 VL 40 BP 139 EP 180 DI 10.1016/B978-0-12-374478-4.00006-X PG 42 WC Education, Special; Neurosciences; Psychology, Multidisciplinary; Rehabilitation SC Education & Educational Research; Neurosciences & Neurology; Psychology; Rehabilitation GA BWU59 UT WOS:000294875600006 ER PT S AU Stokes, WS Kulpa-Eddy, J McFarland, R AF Stokes, William S. Kulpa-Eddy, Jodie McFarland, Richard BE KulpaEddy, J McFarland, R Stokes, WS TI The International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing: introduction and summary SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE veterinary vaccines; human vaccines; ICCVAM; potency testing; safety testing; alternatives ID INACTIVATED RABIES VACCINES; QUALITY-CONTROL; RECOMMENDATIONS; CHALLENGE AB Vaccines contribute to improved animal and human health and welfare by preventing diseases and deaths from infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of available alternative methods and approaches that can further reduce, refine, and replace the use of animals for human and veterinary vaccine potency and safety testing, and to identify research, development, and validation efforts necessary to further advance new and improved alternative methods. Workshop participants identified human and veterinary vaccines that should have the highest priority for future efforts. Prioritization criteria included testing that involves significant pain and distress, large numbers of animals, and pathogens that are dangerous to people and animals. Participants noted that in vitro antigen quantification assays have replaced animals for potency testing for some killed vaccines, and recommended that this approach be expanded to other vaccines. Recommendations to support more humane animal use included development and use of humane endpoints for all challenge tests, development of serologic assays to replace challenge tests, and development of in vitro toxin neutralization tests (TNT) to replace in vivo TNTs. Workshop participants recommended several approaches that might further reduce the number of animals required for specific potency tests. Participants also recommended priority vaccines for which alternative safety testing methods should be pursed and that would have the greatest impact on avoiding pain and distress and reducing animal numbers. Finally, workshop participants recommended enhanced international harmonization and cooperation efforts and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will reduce animal use, benefit animal welfare, and ensure continued and improved protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Stokes, William S.] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. [Kulpa-Eddy, Jodie] US Dept, Agr Anim & Plant Hlth Inspect Serv Vet Serv, Riverdale, MD USA. [McFarland, Richard] US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM stokes@niehs.nih.gov NR 58 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 1 EP 15 DI 10.1016/j.provac.2011.10.001 PG 15 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900001 ER PT S AU McFarland, R Verthelyi, D Casey, W Arciniega, J Isbrucker, R Schmitt, M Finn, T Descamps, J Horiuchi, Y Sesardic, D Stickings, P Johnson, NW Lipscomb, E Allen, D AF McFarland, Richard Verthelyi, Daniela Casey, Warren Arciniega, Juan Isbrucker, Richard Schmitt, Michael Finn, Theresa Descamps, Johan Horiuchi, Yoshinobu Sesardic, Dorothea Stickings, Paul Johnson, Nelson W. Lipscomb, Elizabeth Allen, David BE KulpaEddy, J McFarland, R Stokes, WS TI Non-animal replacement methods for human vaccine potency testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine potency testing; vaccine safety testing; replacement alternatives; ICCVAM ID RABIES VACCINES; ANIMAL-MODELS; UNITED-STATES; COMBINATION; ELISA AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This report addresses methods and strategies identified by workshop participants for replacement of animals used for potency testing of human vaccines. Vaccines considered to have the highest priority for future efforts were (1) vaccines for which antigen quantification methods are already developed but not validated, (2) vaccines/components that require the largest number of animals, (3) vaccines that require an in vivo challenge test, and (4) vaccines with in vivo tests that are highly variable and cause a significant number of invalid tests. Vaccine potency tests identified as the highest priorities for replacement were those for diphtheria and tetanus, pertussis (whole cell and acellular), rabies, anthrax, polio vaccine (inactivated) and complex combination vaccines based on DT or DTwP/aP. Research into understanding the precise mechanism of protection afforded by vaccines and the identification of clinically relevant immunological markers are needed to facilitate the successful implementation of in vitro testing alternatives. This report also identifies several priority human vaccines and associated research objectives that are necessary to successfully implement in vitro vaccine potency testing alternatives. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [McFarland, Richard; Casey, Warren] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [McFarland, Richard; Arciniega, Juan; Schmitt, Michael; Finn, Theresa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Casey, Warren] Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Ctr Evaluat Alternat Toxicol Methods, Natl Toxicol Program Interagency, Morrisville, NC USA. [Isbrucker, Richard] Hlth Canada, Ctr Vaccine Evaluat, Ottawa, ON, Canada. [Descamps, Johan] GlaxoSmithKline Biol, Rixensart, Belgium. [Horiuchi, Yoshinobu] Pharmaceut & Med Devices Agcy Japan, Tokyo, Japan. [Sesardic, Dorothea; Stickings, Paul] Natl Inst Biol Standards & Control, Hlth Protect Agcy, Ridge, England. [Johnson, Nelson W.; Lipscomb, Elizabeth; Allen, David] Integrated Lab Syst Inc, Morrisville, NC USA. RP Casey, W (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM warren.casey@nih.gov NR 70 TC 9 Z9 9 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 16 EP 32 DI 10.1016/j.provac.2011.10.002 PG 17 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900002 ER PT S AU Casey, W Schmitt, M McFarland, R Isbrucker, R Levis, R Arciniega, J Descamps, J Finn, T Hendriksen, C Horiuchi, Y Keller, J Kojima, H Sesardic, D Stickings, P Johnson, NW Lipscomb, E Allen, D AF Casey, Warren Schmitt, Michael McFarland, Richard Isbrucker, Richard Levis, Robin Arciniega, Juan Descamps, Johan Finn, Theresa Hendriksen, Coenraad Horiuchi, Yoshinobu Keller, James Kojima, Hajime Sesardic, Dorothea Stickings, Paul Johnson, Nelson W. Lipscomb, Elizabeth Allen, David BE KulpaEddy, J McFarland, R Stokes, WS TI Improving animal welfare and reducing animal use for human vaccine potency testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine potency testing; vaccine safety testing; refinement alternatives; reduction alternatives; ICCVAM ID QUALITY-CONTROL; VALIDATION AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the third in the series, addresses methods and strategies for human vaccine potency testing that can refine animal use to lessen pain and distress, improve animal welfare, and reduce animal use. Workshop participants agreed that the following potency tests for human vaccines should have the highest priority for development of reduction and/or refinement methods: (1) potency tests for vaccines that are most commonly used, (2) potency tests that require the largest number of animals, (3) potency tests that cause severe animal pain and distress, (4) potency tests where the knowledge base of each antigen is advanced, and (5) potency tests for which alternative methods already exist or are in development. Based on these criteria, the highest-priority human vaccines were identified as diphtheria and tetanus vaccines, pertussis vaccines (whole cell and acellular), rabies vaccine, anthrax vaccine, and complex combination vaccines (containing diphtheria, tetanus, and pertussis together with other antigens such as IPV, Hib, and HepB). For successful implementation of reduction and refinement alternatives, further research is required into the development and broader use of humane endpoints, serological potency methods, and approaches that would reduce the number of animals used in currently approved potency assays. Because the workshop focused on both human and veterinary vaccines, workshop participants also recommended that human vaccine potency testing methods for rabies and tetanus be reviewed for their potential application to the corresponding veterinary vaccines. Participants agreed that achieving broader acceptance and use of alternative methods, requires that the general principles and procedures for the validation of alternative methods for vaccines be standardized/harmonized internationally. The research, development, validation, and harmonization activities recommended at this workshop are expected to lead to new reduction and/or refinement of animal use in human vaccine potency testing methods and more widespread adoption of existing methods that can reduce animal use and improve animal welfare while ensuring the continued safety and efficacy of human vaccines. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Casey, Warren] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Schmitt, Michael; McFarland, Richard; Levis, Robin; Arciniega, Juan; Finn, Theresa; Keller, James] United States Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD USA. [Isbrucker, Richard] Hlth Canada, Ctr Vaccine Evalut, Ottawa, ON, Canada. [Descamps, Johan] GlaxoSmithKline Biol, Rixensart, Belgium. [Hendriksen, Coenraad] Netherlands Vaccine Inst, Bilthoven, Netherlands. [Horiuchi, Yoshinobu] Pharmaceut & Med Devices Agcy, Tokyo, Japan. [Kojima, Hajime] Japanese Ctr Validat Alternat Methods, Tokyo, Japan. [Sesardic, Dorothea; Stickings, Paul] Natl Inst Biol Stand & Controls, Hlth Protect Agcy, Hertford, England. [Johnson, Nelson W.; Lipscomb, Elizabeth; Allen, David] Integrated Syst Lab Inc, Res Triangle Pk, NC USA. RP Casey, W (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM warren.casey@nih.gov NR 66 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 33 EP 46 DI 10.1016/j.provac.2011.10.003 PG 14 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900003 ER PT S AU Kulpa-Eddy, J Srinivas, G Halder, M Brown, K Draayer, H Galvin, J Claassen, I Gifford, G Woodland, R Doelling, V Jones, B Stokes, WS AF Kulpa-Eddy, Jodie Srinivas, Geetha Halder, Marlies Brown, Karen Draayer, Hans Galvin, Jeffrey Claassen, Ivo Gifford, Glen Woodland, Ralph Doelling, Vivian Jones, Brett Stokes, William S. BE KulpaEddy, J McFarland, R Stokes, WS TI Alternative methods and strategies to reduce, refine, and replace animal use for veterinary vaccine post-licensing safety testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE veterinary vaccines; vaccine safety testing; alternative methods; refinement; reduction; replacement; ICCVAM ID QUALITY-CONTROL AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the last in the series, addresses methods and strategies for veterinary vaccine post-licensing safety testing that can reduce, refine, and replace animal use (the 3Rs). It also provides recommendations for priority research and other activities necessary to advance the development and/or implementation of 3Rs methods for veterinary vaccine post-licensing safety testing. Workshop participants gave priority for future efforts to vaccines that (1) use large numbers of animals per test, (2) produce large numbers of serials annually, (3) use additional animals for safety testing. They also prioritized poultry vaccines for which in vivo extraneous agent testing is still performed, adjuvanted vaccines that cause a site reaction, and vaccines that are well characterized. Vaccines identified as the highest priorities were those for avian diseases, rabies, Clostridium spp., and subunit protein and DNA vaccines, in addition to modified live viral products that do not contain excipients. Workshop participants recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included further assessment of the need for a general safety test; expanded application of primary cell culture and polymerase chain reaction (PCR) techniques to replace in vivo chicken tests for extraneous agents; development of in-process safety testing to verify detoxification of selected vaccines; and further investigation of cell-based assays to measure residual toxicity. Implementation of the workshop recommendations is expected to advance alternative methods for veterinary vaccine post-licensing safety testing that will benefit animal welfare and reduce or replace animal use while ensuring continued protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Stokes, William S.] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Kulpa-Eddy, Jodie] US Dept, Agr Anim & Plant Hlth Inspect Serv, Vet Serv, Riverdale, MD USA. [Srinivas, Geetha] US Dept, Agr Anim & Plant Hlth Inspect Serv, Ctr Vet Biol, Ames, IA USA. [Halder, Marlies] European Ctr Validat Alternat Methods, Inst Hlth & Consumer Protect, Eurpean Commiss Joint Res Ctr, Ispra, Italy. [Brown, Karen] Pair ODocs Enterprises, Parkville, MI USA. [Draayer, Hans] Pfizer Anim Hlth, Lincoln, NE USA. [Claassen, Ivo] Cent Vet Inst, Lelystad, Netherlands. [Gifford, Glen] Canadian Food Inspect Agcy, Canadian Ctr Vet Biol, Ottawa, ON, Canada. [Woodland, Ralph] Vet Medicines Directorate, Surrey, England. [Doelling, Vivian; Jones, Brett] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM stokes@niehs.nih.gov NR 42 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 47 EP 59 DI 10.1016/j.provac.2011.10.004 PG 13 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900004 ER PT S AU Kulpa-Eddy, J Srinivas, G Halder, M Hill, R Brown, K Roth, J Draayer, H Galvin, J Claassen, I Gifford, G Woodland, R Doelling, V Jones, B Stokes, WS AF Kulpa-Eddy, Jodie Srinivas, Geetha Halder, Marlies Hill, Richard Brown, Karen Roth, James Draayer, Hans Galvin, Jeffrey Claassen, Ivo Gifford, Glen Woodland, Ralph Doelling, Vivian Jones, Brett Stokes, William S. BE KulpaEddy, J McFarland, R Stokes, WS TI Non-animal replacement methods for veterinary vaccine potency testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE veterinary vaccines; vaccine potency testing; vaccine safety testing; replacement alternatives; ICCVAM ID MOUTH-DISEASE VIRUS; INACTIVATED RABIES VACCINES; QUALITY-CONTROL; ERYSIPELAS VACCINES; CLINICAL-PROTECTION; ANTIGEN; CHALLENGE; RECOMMENDATIONS; QUANTIFICATION; VALIDATION AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Six topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the second in the series, provides recommendations for current and future use of non-animal methods and strategies for veterinary vaccine potency testing. Workshop participants recommended that future efforts to replace animal use give priority to vaccines (1) that use large numbers of animals per test and for which many serials are produced annually, (2) that involve significant animal pain and distress during procedures, (3) for which the functional protective antigen has been identified, (4) that involve foreign animal/zoonotic organisms that are dangerous to humans, and (5) that involve pathogens that can be easily spread to wildlife populations. Vaccines identified as the highest priorities were those for rabies, Leptospira spp., Clostridium spp., Erysipelas, foreign animal diseases (FAD), poultry diseases, and fish diseases. Further research on the identification, purification, and characterization of vaccine protective antigens in veterinary vaccines was also identified as a priority. Workshop participants recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations included (1) investigations into the relative impact of various adjuvants on antigen quantification assays, (2) investigations into extraction methods that could be used for vaccines containing adjuvants that can interfere with antigen assays, and (3) review of the current status of rabies and tetanus human vaccine in vitro potency methods for their potential application to the corresponding veterinary vaccines. Workshop participants recommended enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for veterinary vaccine potency testing that will benefit animal welfare and replace animal use while ensuring continued protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Stokes, William S.] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Kulpa-Eddy, Jodie] US Dept, Agr Anim & Plant Hlth Inspect, Vet Serv, Riverdale, MD USA. [Srinivas, Geetha; Hill, Richard] US Dept, Agr Anim & Plant Hlth Inspect, Ctr Vet Biol, Ames, IA USA. [Halder, Marlies] Inst Hlth & Consumer Protect, European Ctr Validat Alternat Methods, European Commiss Joint Res Ctr, Ispra, Italy. [Roth, James] Pair ODocs Enterprises, Parkville, MI USA. [Draayer, Hans] Iowa State Univ, Coll Vet Med, Ctr Food Safety Secur & Publ Hlth, Ames, IA USA. [Galvin, Jeffrey] Pfizer Anim Hlth, Lincoln, NE USA. [Claassen, Ivo] Cent Vet Inst, Lelystad, Netherlands. [Gifford, Glen] Canadian Food Inspect Agcy, Canadian Ctr Vet Biol, Ottawa, ON, Canada. [Woodland, Ralph] Vet Medicines Directorate, Surrey, England. [Doelling, Vivian; Jones, Brett] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM stokes@niehs.nih.gov NR 80 TC 11 Z9 12 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 60 EP 83 DI 10.1016/j.provac.2011.10.005 PG 24 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900005 ER PT S AU Stokes, WS Brown, K Kulpa-Eddy, J Srinivas, G Halder, M Draayer, H Galvin, J Claassen, I Gifford, G Woodland, R Doelling, V Jones, B AF Stokes, William S. Brown, Karen Kulpa-Eddy, Jodie Srinivas, Geetha Halder, Marlies Draayer, Hans Galvin, Jeffrey Claassen, Ivo Gifford, Glen Woodland, Ralph Doelling, Vivian Jones, Brett BE KulpaEddy, J McFarland, R Stokes, WS TI Improving animal welfare and reducing animal use for veterinary vaccine potency testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE veterinary vaccines; vaccine potency testing; vaccine safety testing; refinement alternatives; reduction alternatives; ICCVAM ID INACTIVATED RABIES VACCINES; HUMANE END-POINTS; QUALITY-CONTROL; ERYSIPELAS VACCINES; NEUTRALIZATION TEST; VALIDATION; CHALLENGE; ELISA AB Veterinary vaccines contribute to improved human and animal health and welfare by preventing diseases and deaths caused by a wide range of infectious agents. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This workshop report is the fourth in a series of six, and addresses methods and strategies for veterinary vaccine potency testing that can avoid or lessen pain and distress, improve animal welfare, and reduce animal use. Vaccine potency tests considered to have the highest priority for further reduction and refinement were those that require an infectious agent challenge test or an in vivo toxin neutralization test, those that require large numbers of animals, and those that require the use of infectious agents hazardous to laboratory workers and/or animals. Vaccines identified as high priorities for improved alternative test methods were rabies, Clostridium spp., Leptospira spp., foreign animal diseases (e.g., foot and mouth disease), and poultry and fish vaccines. The workshop recommended priority research, development, and validation activities to address critical knowledge and data gaps, including opportunities to apply new science and technology. Recommendations to support more humane animal use included development and use of humane endpoints for all challenge tests, development of serologic assays to replace challenge tests, and development of in vitro toxin neutralization tests to replace in vivo TNTs. Workshop participants recommended approaches to reduce the number of animals required for potency testing, and recommended enhanced international harmonization and cooperation, and closer collaborations between human and veterinary researchers to expedite progress in the development and application of alternative methods. Implementation of the workshop recommendations is expected to advance new methods for veterinary vaccine potency testing that will benefit animal welfare and reduce animal use while ensuring continued protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Stokes, William S.] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Brown, Karen] Pair ODocs Enterprises, Parkville, MI USA. [Kulpa-Eddy, Jodie] US Dept, Agr Anim & Plant Hlth Inspect Serv, Vet Serv, Riverdale, MD USA. [Srinivas, Geetha] US Dept, Agr Anim & Plant Hlth Inspect Serv, Ctr Vet Biol, Ames, IA USA. [Halder, Marlies] Inst Hlth & Consumer Protect, European Ctr Validat Alternat Methods, European Commiss Joint Res Ctr, Ispra, Italy. [Draayer, Hans; Galvin, Jeffrey] Pfizer Anim Hlth, Lincoln, NE USA. [Claassen, Ivo] Cent Vet Inst, Lelystad, Netherlands. [Gifford, Glen] Canadian Food Inspect Agcy, Canadian Ctr Vet Biol, Ottawa, ON, Canada. [Woodland, Ralph] Vet Medicines Directorate, Surrey, England. [Doelling, Vivian; Jones, Brett] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM stokes@niehs.nih.gov NR 82 TC 10 Z9 10 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 84 EP 105 DI 10.1016/j.provac.2011.10.006 PG 22 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900006 ER PT S AU Isbrucker, R Levis, R Casey, W McFarland, R Schmitt, M Arciniega, J Descamps, J Finn, T Hendriksen, C Horiuchi, Y Keller, J Kojima, H Sesardic, D Stickings, P Johnson, NW Allen, D AF Isbrucker, Richard Levis, Robin Casey, Warren McFarland, Richard Schmitt, Michael Arciniega, Juan Descamps, Johan Finn, Theresa Hendriksen, Coenraad Horiuchi, Yoshinobu Keller, James Kojima, Hajime Sesardic, Dorothea Stickings, Paul Johnson, Nelson W. Allen, David BE KulpaEddy, J McFarland, R Stokes, WS TI Alternative methods and strategies to reduce, refine, and replace animal use for human vaccine post-licensing safety testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine safety testing; vaccine potency testing; 3Rs alternatives; ICCVAM ID QUALITY-CONTROL; PERTUSSIS TOXIN; POLIOVIRUS; ENDOTOXIN; ASSAY AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use (the 3Rs). Six topics were addressed in detail by speakers and workshop participants and are reported in a series of reports. This workshop report, the fifth in the series, addresses methods and strategies for human vaccine post-licensing safety testing that can reduce, refine, and replace animal use. It also provides recommendations for priority research and other activities necessary to advance the development and/or implementation of 3Rs methods for human vaccine post-licensing safety testing. Workshop participants agreed that future 3Rs activities should give highest priority to vaccine safety tests that (1) use the most animals per test and for which many vaccine lots are tested annually, (2) produce high variability and/or require frequent repeat tests, (3) are associated with severe animal pain and distress, and/or (4) involve nonhuman primates. Based on these criteria, safety tests for diphtheria, pertussis, oral polio, and tetanus vaccines were identified as the highest priorities. Recommended priority research, development, and validation activities included (1) expanding use of the transgenic mouse model for oral polio vaccine, and (2) developing alternatives to the monkey neurovirulence test for preclinical safety and lot release neurovirulence testing of mumps vaccines. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for human vaccine post-licensing safety testing that will benefit animal welfare while ensuring continued production of safe human vaccines and protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Casey, Warren] NIEHS, Natl Toxicol Program Interagency Ctr, Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, Res Triangle Pk, NC USA. [Isbrucker, Richard] Hlth Canada, Ctr Vaccine Evaluat, Ottawa, ON, Canada. [Levis, Robin; McFarland, Richard; Schmitt, Michael; Arciniega, Juan; Finn, Theresa; Keller, James] US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. [Descamps, Johan] GlaxoSmithKline Biol, Rixensart, Belgium. [Hendriksen, Coenraad] Netherlands Vaccine Inst, Bilthoven, Netherlands. [Horiuchi, Yoshinobu] Pharmaceut & Med Devices Agcy Japan, Tokyo, Japan. [Kojima, Hajime] Japanese Ctr Validat Alternat Methods, Tokyo, Japan. [Sesardic, Dorothea; Stickings, Paul] Natl Inst Biol Stand & Controls, Hlth Protect Agcy, Hertford, England. [Johnson, Nelson W.; Allen, David] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Casey, W (reprint author), NIEHS, Natl Toxicol Program Interagency Ctr, Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, Res Triangle Pk, NC USA. EM warren.casey@nih.gov NR 66 TC 9 Z9 9 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 106 EP 119 DI 10.1016/j.provac.2011.10.004 PG 14 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900007 ER PT S AU Maojo, V Garcia-Remesal, M de la Iglesia, D Crespo, J Perez-Rey, D Chiesa, S Fritts, M Kulikowski, CA AF Maojo, Victor Garcia-Remesal, Miguel de la Iglesia, Diana Crespo, Jose Perez-Rey, David Chiesa, Stefano Fritts, Martin Kulikowski, Casimir A. BE Prokop, A TI Nanoinformatics: Developing Advanced Informatics Applications for Nanomedicine SO INTRACELLULAR DELIVERY: FUNDAMENTALS AND APPLICATIONS SE Fundamental Biomedical Technologies LA English DT Article; Book Chapter DE Nanomedicine; Biomedical Informatics; Nanoinformatics; Nanoparticles; Nanoresources; Nanotoxicity; Data Integration; Ontologies; Semantic search; Modeling and Simulation ID MEDICAL INFORMATICS; HEALTH INFORMATICS; TEXT; ONTOLOGY; BIOINFORMATICS; RECOGNITION; INTEGRATION; DATABASES; PROTEIN; MODEL AB In this chapter we introduce a new informatics field called "Nanoinformatics" based on our own research and on consensus work carried out under the auspices of the US National Cancer Institute (NCI) and the European Commission (EC). Nanoinformatics can be defined as the "use of informatics techniques for analyzing and processing information about the structure and physicochemical characteristics of nanoparticles, their environments, and applications". Its goal is to use information to accelerate research in nanomedicine. We summarize various areas of research and applications, such as ontologies and semantic search, text mining, imaging, standards, together with an example of the research our group has performed in this field on text mining for extracting information about nanotoxicity from the literature. C1 [Maojo, Victor; Garcia-Remesal, Miguel; de la Iglesia, Diana; Crespo, Jose; Perez-Rey, David; Chiesa, Stefano] Univ Politecn Madrid, Dept Inteligencia Artificial, Fac Informat, Biomed Informat Grp, Madrid, Spain. [Fritts, Martin] NCI, Nanotechnol Characterizat Lab, US Natl Inst Hlth, Baltimore, MD USA. [Fritts, Martin] NCI, SAIC Frederick Comp Sci, US Natl Inst Hlth, Baltimore, MD USA. [Kulikowski, Casimir A.] Rutgers State Univ, Dept Comp Sci, Newark, NJ 07102 USA. RP Maojo, V (reprint author), Univ Politecn Madrid, Dept Inteligencia Artificial, Fac Informat, Biomed Informat Grp, Campus Montegancedo, Madrid, Spain. EM vmaojo@fi.upm.es RI Perez-Rey, David/B-8172-2009; Garcia-Remesal, Miguel/G-3147-2013 OI Perez-Rey, David/0000-0002-9021-2597; Garcia-Remesal, Miguel/0000-0002-7532-9471 NR 37 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1559-7083 BN 978-94-007-1247-8 J9 FUND BIOMED TECHNOL JI Fundam. Biomed. Technol. PY 2011 VL 5 BP 847 EP 860 DI 10.1007/978-94-007-1248-5_26 D2 10.1007/978-94-007-1248-5 PG 14 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA BVR96 UT WOS:000292617300026 ER PT J AU Brodie, B Pokharel, Y Fleishman, N Bensimhon, A Kissling, G Hansen, C Milks, S Cooper, M McAlhany, C Stuckey, T AF Brodie, Bruce Pokharel, Yashashwi Fleishman, Nathan Bensimhon, Adam Kissling, Grace Hansen, Charles Milks, Sally Cooper, Michael McAlhany, Christopher Stuckey, Tom TI Very Late Stent Thrombosis After Primary Percutaneous Coronary Intervention With Bare-Metal and Drug-Eluting Stents for ST-Segment Elevation Myocardial Infarction A 15-Year Single-Center Experience SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE percutaneous coronary intervention; stent thrombosis; ST-segment elevated myocardial infarction ID CLINICAL-TRIALS; UNCOATED STENTS; MANAGEMENT AB Objectives The purpose of this study was to assess the frequency of very late stent thrombosis (VLST) after stenting with bare-metal stents (BMS) and drug-eluting stents (DES) for ST-segment elevation myocardial infarction (STEMI). Background Stent thrombosis occurs more frequently after stenting for STEMI than after elective stenting, but there are little data regarding VLST. Methods Consecutive patients (n = 1,463) who underwent stenting for STEMI were prospectively enrolled in our database. BMS were implanted exclusively from 1995 to 2002, and DES and BMS were implanted from 2003 to 2009. Follow-up was obtained at 1 to 15 years. Results BMS patients (n = 1,095) were older and had more shock, whereas DES patients (n = 368) had more diabetes and smaller vessels. Stent thrombosis occurred in 107 patients, of which 42 were VLST (>1 year). Stent thrombosis continued to increase to at least 11 years with BMS and to at least 4.5 years with DES. Stent thrombosis rates with BMS versus DES were similar at 1 year (5.1% and 4.0%, respectively) but increased more with DES after the first year (1.9%/year vs. 0.6%/year, respectively). Landmark analysis (>1 year) found DES had a higher frequency of VLSI (p < 0.001) and reinfarction (p = 0.003). DES was the only significant independent predictor of VLST (hazard ratio: 3.79, 95% confidence interval: 1.64 to 8.79, p = 0.002). Conclusions VLST after primary PCI for STEN occurs with relatively high frequency to at least 11 years with BMS and to at least 4.5 years with DES. Very late stent thrombosis and reinfarction (>1 year) were more frequent with DES. New strategies are needed to manage this problem. (J Am Coll Cardiol Intv 2011;4:30-8) (C) 2011 by the American College of Cardiology Foundation C1 [Brodie, Bruce; Fleishman, Nathan; Bensimhon, Adam; Milks, Sally; Cooper, Michael; McAlhany, Christopher; Stuckey, Tom] Moses Cone Mem Hosp, LeBauer Cardiovasc Res Fdn, Greensboro, NC 27408 USA. [Kissling, Grace] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Pokharel, Yashashwi; Hansen, Charles] Moses Cone Mem Hosp, Internal Med Residency Program, Greensboro, NC 27408 USA. RP Brodie, B (reprint author), Moses Cone Mem Hosp, LeBauer Cardiovasc Res Fdn, 313 Meadowbrook Terrace, Greensboro, NC 27408 USA. EM bbrodie@triad.rr.com FU LeBauer Charitable Research Foundation; National Institutes of Health, National Institute of Environmental Health Sciences [Z01ES045005] FX This study was supported by an unrestricted grant from the LeBauer Charitable Research Foundation. This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (Z01ES045005). Dr. Brodie has served on the Speakers' Bureau for The Medicines Company and Medrad/Possis. Dr. Stuckey has served as consultant and on the Speakers' Bureau and Advisory Board for Boston Scientific Corporation. All other authors have reported that they have no relationships to disclose. NR 24 TC 47 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD JAN PY 2011 VL 4 IS 1 BP 30 EP 38 DI 10.1016/j.jcin.2010.11.004 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 719EA UT WOS:000287181500004 PM 21251626 ER PT J AU Baker, JV Neuhaus, J Duprez, D Kuller, LH Tracy, R Belloso, WH De Wit, S Drummond, F Lane, HC Ledergerber, B Lundgren, J Nixon, DE Paton, NI Neaton, JD AF Baker, Jason V. Neuhaus, Jacqueline Duprez, Daniel Kuller, Lewis H. Tracy, Russell Belloso, Waldo H. De Wit, Stephane Drummond, Fraser Lane, H. Clifford Ledergerber, Bruno Lundgren, Jens Nixon, Daniel E. Paton, Nicholas I. Neaton, James D. CA INSIGHT SMART Study Grp TI Changes in Inflammatory and Coagulation Biomarkers: A Randomized Comparison of Immediate versus Deferred Antiretroviral Therapy in Patients With HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV infection; antiretroviral therapy; inflammation; coagulation; biomarkers; cardiovascular disease; non-AIDS conditions ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; IMMUNE ACTIVATION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK; VIRAL REPLICATION; MARKERS; MORTALITY; INTERLEUKIN-6; DEATH AB Objectives: Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naive to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re) initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. Methods: Stored specimens for 254 participants (126 drug conservation [DC] and 128 viral suppression [VS]) who were naive to ART or off ART (6 months or longer) were analyzed for interleukin-6, high sensitivity C-reactive protein, and D-dimer at baseline and Months 2 and 6. Results: At Month 6, 62% of the VS group had HIV RNA less than 400 copies/mL and median CD4 count was 190 cells/mm(3) higher than for the DC group (590 versus 400 cells/mm(3)). Compared with DC, the VS group had 32% (95% confidence interval, 19%-43%) lower D-dimer levels at Month 6 (P < 0.001); differences were not significant for high sensitivity C-reactive protein or interleukin-6 levels. Conclusions: In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not interleukin-6 and high sensitivity C-reactive protein, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection. C1 [Baker, Jason V.; Neuhaus, Jacqueline; Duprez, Daniel; Neaton, James D.] Univ Minnesota, Minneapolis, MN USA. [Baker, Jason V.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Kuller, Lewis H.] Univ Pittsburgh, Pittsburgh, PA USA. [Tracy, Russell] Univ Vermont, Burlington, VT USA. [Belloso, Waldo H.] Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina. [De Wit, Stephane] Hop St Pierre & Erasme, Brussels, Belgium. [Drummond, Fraser] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Lane, H. Clifford] NIAID, NIH, Bethesda, MD 20892 USA. [Ledergerber, Bruno] Univ Zurich, Univ Hosp, Zurich, Switzerland. [Lundgren, Jens] Univ Copenhagen, Copenhagen, Denmark. [Nixon, Daniel E.] Virginia Commonwealth Univ, Richmond, VA USA. [Paton, Nicholas I.] MRC, Clin Trials Unit, London, England. RP Baker, JV (reprint author), 701 Pk Ave,MC G5, Minneapolis, MN 55415 USA. EM baker459@umn.edu RI Infektiologie, USZ/A-6921-2011; Ledergerber, Bruno/B-5656-2009; OI Ledergerber, Bruno/0000-0002-6881-4401; Lundgren, Jens/0000-0001-8901-7850 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [U01AI042170, U01AI46362]; National Institutes of Health, National Heart, Lung and Blood Institute [HL 090934-01]; Gilead; GlaxoSmithKline; Aviir; Abbott; Merck; GlaxoSmithKline/diaDexus; Celera Diagnostics; Aventis; Bristol-Myers Squibb; Sharp Dohme; Roche; Tibotec; Boehringer-Ingelheim; Pfizer FX Support provided by National Institutes of Health grants: National Institute of Allergy and Infectious Diseases U01AI042170 and U01AI46362 and National Heart, Lung and Blood Institute HL 090934-01.; J.V.B. reported research grants or honoraria from Gilead and GlaxoSmithKline. R.T. reported the following activities: honoraria or grant support from Aviir, Abbott, Merck, GlaxoSmithKline/diaDexus, amd Celera Diagnostics; external advisory board for Wake Forest University Pepper Center on Aging, Johns Hopkins University Pepper Center on Aging, and University of Florida Pepper Center on Aging; owner of Haematologic Technologies; thrombosis and fibrinolysis biochemical reagents and blood collection tubes; contract research in this area; and Ashcraft & Gerel Attorneys at Law consulting on mechanisms in inflammation, atherosclerosis, and thrombosis. S.D. reported honoraria from GlaxoSmithKline, Bristol-Myers Squibb, and Pfizer. B.L. reported research grants or honoraria from Abbott, Aventis, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Sharp & Dohme, Roche, and Tibotec. J.L. reported honoraria and research grants from Boehringer-Ingelheim, Roche, Abbott, Bristol-Myers Squibb, Merck, Sharp & Dohme, GlaxoSmithKline, Tibotec, Pfizer, and Gilead. NR 44 TC 74 Z9 74 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JAN 1 PY 2011 VL 56 IS 1 BP 36 EP 43 DI 10.1097/QAI.0b013e3181f7f61a PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 692XC UT WOS:000285188200012 PM 20930640 ER PT J AU Mariotto, AB Yabroff, KR Shao, YW Feuer, EJ Brown, ML AF Mariotto, Angela B. Yabroff, K. Robin Shao, Yongwu Feuer, Eric J. Brown, Martin L. TI Projections of the Cost of Cancer Care in the United States: 2010-2020 SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; COLORECTAL-CANCER; SURVIVAL AB Background Current estimates of the costs of cancer care in the United States are based on data from 2003 and earlier. However, incidence, survival, and practice patterns have been changing for the majority of cancers. Methods Cancer prevalence was estimated and projected by phase of care (initial year following diagnosis, continuing, and last year of life) and tumor site for 13 cancers in men and 16 cancers in women through 2020. Cancer prevalence was calculated from cancer incidence and survival models estimated from Surveillance, Epidemiology, and End Results (SEER) Program data. Annualized net costs were estimated from recent SEER-Medicare linkage data, which included claims through 2006 among beneficiaries aged 65 years and older with a cancer diagnosis. Control subjects without cancer were identified from a 5% random sample of all Medicare beneficiaries residing in the SEER areas to adjust for expenditures not related to cancer. All cost estimates were adjusted to 2010 dollars. Different scenarios for assumptions about future trends in incidence, survival, and cost were assessed with sensitivity analysis. Results Assuming constant incidence, survival, and cost, we projected 13.8 and 18.1 million cancer survivors in 2010 and 2020, respectively, with associated costs of cancer care of 124.57 and 157.77 billion 2010 US dollars. This 27% increase in medical costs reflects US population changes only. The largest increases were in the continuing phase of care for prostate cancer (42%) and female breast cancer (32%). Projections of current trends in incidence (declining) and survival (increasing) had small effects on 2020 estimates. However, if costs of care increase annually by 2% in the initial and last year of life phases of care, the total cost in 2020 is projected to be $173 billion, which represents a 39% increase from 2010. Conclusions The national cost of cancer care is substantial and expected to increase because of population changes alone. Our findings have implications for policy makers in planning and allocation of resources. C1 [Mariotto, Angela B.; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Yabroff, K. Robin; Brown, Martin L.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Shao, Yongwu] Informat Management Serv Inc, Silver Spring, MD USA. RP Mariotto, AB (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Ste 504,MSC 8317,6116 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM mariotta@mail.nih.gov NR 25 TC 614 Z9 626 U1 5 U2 31 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JAN PY 2011 VL 103 IS 2 BP 117 EP 128 DI 10.1093/jnci/djq495 PG 12 WC Oncology SC Oncology GA 709WT UT WOS:000286472800009 PM 21228314 ER PT J AU Radtke, JV AF Radtke, Jill V. TI The Paradox of Breastfeeding-Associated Morbidity Among Late Preterm Infants SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Review DE prematurity; premature birth; late preterm; breast feeding; lactation; morbidity ID NEAR-TERM INFANTS; BIRTH-WEIGHT INFANTS; 36 WEEKS GESTATION; PREMATURE-INFANTS; RISK-FACTORS; NEONATAL MORBIDITY; LACTOGENESIS-II; EARLY DISCHARGE; UNITED-STATES; HUMAN-MILK AB Objective To synthesize the published research pertaining to breastfeeding establishment and outcomes among late preterm infants and to describe the state of the science on breastfeeding within this population. Data Sources Online databases Ovid MEDLINE, CINAHL, PubMed, and reference lists of reviewed articles. Study Selection Nine data-based research articles examining breastfeeding patterns and outcomes among infants born between 34 0/7 and 36 6/7 weeks gestation or overlapping with this time period by at least 2 weeks. Data Extraction Effect sizes and descriptive statistics pertaining to breastfeeding initiation, duration, exclusivity, and health outcomes among late preterm breastfed infants. Data Synthesis Among late preterm mother/infant dyads, breastfeeding initiation appears to be approximately 59% to 70% (U.S.), whereas the odds of breastfeeding beyond 4 weeks or to the recommended 6 months (exclusive breastfeeding) appears to be significantly less than for term infants, and possibly less than infants < 34 to 35 weeks gestation. Breastfeeding exclusivity is not routinely reported. Rehospitalization, often related to "jaundice" and "poor feeding," is nearly twice as common among late preterm breastfed infants as breastfed term or nonbreastfed late preterm infants. Barriers to optimal breastfeeding in this population are often inferred from research on younger preterm infants, and evidence-based breastfeeding guidelines are lacking. Conclusions Late preterm infants are at greater risk for breastfeeding-associated rehospitalization and poor breastfeeding establishment compared to their term (and possibly early preterm) counterparts. Contributing factors have yet to be investigated systematically. C1 Univ Pittsburgh, Sch Nursing, Natl Inst Nursing Res, Pittsburgh, PA 15261 USA. RP Radtke, JV (reprint author), Univ Pittsburgh, Sch Nursing, Natl Inst Nursing Res, 336 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. EM jvr5@pitt.edu FU National Institute of Nursing Research [1F31NR011562] FX Funded by National Institute of Nursing Research grant 1F31NR011562. NR 88 TC 22 Z9 23 U1 3 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD JAN-FEB PY 2011 VL 40 IS 1 BP 9 EP 24 DI 10.1111/j.1552-6909.2010.01211.x PG 16 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 707ZZ UT WOS:000286331400003 PM 21244492 ER PT J AU Rovner, AJ Nansel, TR Wang, J Iannotti, RJ AF Rovner, Alisha J. Nansel, Tonja R. Wang, Jing Iannotti, Ronald J. TI Food Sold in School Vending Machines Is Associated With Overall Student Dietary Intake SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Schools; Vending machines; food of minimal nutritional value ID HEALTH BEHAVIOR; US CHILDREN; ADOLESCENTS; INDICATORS AB Purpose: To examine the association between food sold in school vending machines and the dietary behaviors of students. Methods: The 2005-2006 U.S. Health Behavior in School-aged Children survey was administered to 6th to 10th graders and school administrators. Dietary intake in students was estimated with a brief food frequency measure. School administrators completed questions regarding food sold in vending machines. For each food intake behavior, a multilevel regression analysis modeled students (level 1) nested within schools (level 2), with the corresponding food sold in vending machines as the main predictor. Control variables included gender, grade, family affluence, and school poverty index. Analyses were conducted separately for 6th to 8th and 9th-10th grades. Results: In all, 83% of the schools (152 schools; 5,930 students) had vending machines that primarily sold food of minimal nutritional values (soft drinks, chips, and sweets). In younger grades, availability of fruit and/or vegetables and chocolate and/or sweets was positively related to the corresponding food intake, with vending machine content and school poverty index providing an explanation for 70.6% of between-school variation in fruit and/or vegetable consumption and 71.7% in sweets consumption. Among the older grades, there was no significant effect of food available in vending machines on reported consumption of those food. Conclusion: Vending machines are widely available in public schools in the United States. In younger grades, school vending machines were either positively or negatively related to the diets of the students, depending on what was sold in them. Schools are in a powerful position to influence the diets of children; therefore, attention to the food sold at school is necessary to try to improve their diets. (C) 2011 Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Rovner, Alisha J.; Nansel, Tonja R.; Wang, Jing; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Iannotti, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, US Dept HHS, NIH, 6100 Execut Blvd Room 7B13Q,MSC 7510, Bethesda, MD 20892 USA. EM iannottr@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Maternal and Child Health Bureau of the Health Resources and Services Administration FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Maternal and Child Health Bureau of the Health Resources and Services Administration. NR 26 TC 27 Z9 28 U1 3 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD JAN PY 2011 VL 48 IS 1 BP 13 EP 19 DI 10.1016/j.jadohealth.2010.08.021 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 698XT UT WOS:000285629200005 PM 21185519 ER PT J AU Calderon, MA Casale, TB Togias, A Bousquet, J Durham, SR Demoly, P AF Calderon, Moises A. Casale, Thomas B. Togias, Alkis Bousquet, Jean Durham, Stephen R. Demoly, Pascal TI Allergen-specific immunotherapy for respiratory allergies: From meta-analysis to registration and beyond SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Specific immunotherapy; allergic rhinitis; allergic asthma; allergens ID POLLEN-INDUCED RHINOCONJUNCTIVITIS; TERM CLINICAL-EFFICACY; SUBLINGUAL IMMUNOTHERAPY; DOUBLE-BLIND; SYMPTOMATIC TREATMENT; ECONOMIC-EVALUATION; PEDIATRIC-PATIENTS; POSITION PAPER; DOUBLE-DUMMY; RHINITIS AB Allergen-specific immunotherapy (SIT) is an etiology-based treatment for respiratory and Hymenoptera-allergic diseases. Although introduced a century ago, SIT was not widely accepted for many years until its efficacy in the treatment of both allergic rhinoconjunctivitis and allergic asthma was demonstrated in appropriate double-blind, placebo-controlled trials and its mechanism of action was better understood. The indications for allergen-specific immunotherapy have been specified in consensus reports. Allergen-specific immunotherapy is primarily targeted to benefit patients with Hymenoptera allergy or severe upper and mild to moderate lower allergic respiratory diseases that are poorly controlled by pharmacologic treatments or who are unable or unwilling to use the latter. Several recent developments have helped to reinforce the position of SIT in the overall therapeutic management of respiratory allergies: (1) improvement in the quality of allergen extracts as a result of standardization, (2) better understanding of SIT's mechanism of action, (3) the introduction of sublingual tablets and their rigorous registration as pharmaceutical therapies by regulatory agencies, and (4) rationalization of prescribing patterns. There is a requirement for additional well designed, well executed, randomized trials in adults and children with allergic rhinitis and asthma, with a special focus on optimal patient selection, dosage, and treatment duration. In this review, the authors put into perspective current international expert recommendations on the use of SIT (in relation to levels of clinical evidence) and analyze what is needed for the future. (J Allergy Clin Immunol 2011;127:30-8.) C1 [Calderon, Moises A.; Durham, Stephen R.] Univ London Imperial Coll Sci Technol & Med, Sect Allergy & Clin Immunol, NHLI, Royal Brompton Hosp, London SW3 6LY, England. [Casale, Thomas B.] Creighton Univ, Omaha, NE 68178 USA. [Togias, Alkis] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Bousquet, Jean] CESP INSERM, Villejuif, France. [Bousquet, Jean; Demoly, Pascal] Univ Hosp Montpellier, Hop Arnaud Villeneuve, Dept Allergy, Montpellier, France. [Bousquet, Jean; Demoly, Pascal] INSERM, U657, F-75654 Paris 13, France. RP Calderon, MA (reprint author), Univ London Imperial Coll Sci Technol & Med, Sect Allergy & Clin Immunol, NHLI, Dovehouse St, London SW3 6LY, England. EM m.calderon@imperial.ac.uk RI Casale, Thomas/K-4334-2013; Osborne, Nicholas/N-4915-2015 OI Casale, Thomas/0000-0002-3149-7377; Osborne, Nicholas/0000-0002-6700-2284 FU Creighton University from Schering-Plough; Stallergenes; Imperial College; ALK from ALK-Abello FX M. A. Calderon and A. Togias declare no relevant conflicts of interest. T. B. Casale is on an advisory board for Stallergenes, has received research support (via Creighton University) from Schering-Plough and Stallergenes, and is on the board of directors of the World Allergy Organization. J. Bousquet has received honoraria for scientific and advisory boards, lectures during meetings, and/or press conferences from Stallergenes, Actelion, Almirall, Astra-Zeneca, Chiesi, GSK, Merck, MSD, Novartis, OM Pharma, Sanofi Aventis, Schering-Plough, Teva, and Uriach. S. R. Durham has given lectures and consulted for ALK-Abello, has consulted for Schering-Plough (now Merck), has received research support (via Imperial College) from ALK-Abello, and is a member of the World Allergy Organization and the European Academy of Allergy and Clinical Immunology's subcommittees on immunotherapy. P. Demoly has received speaker honoraria and consulting fees from ALK and Stallergenes and research support from Stallergenes. NR 86 TC 94 Z9 101 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2011 VL 127 IS 1 BP 30 EP 38 DI 10.1016/j.jaci.2010.08.024 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 702SY UT WOS:000285917300004 PM 20965551 ER PT J AU Busse, WW Peters, SP Fenton, MJ Mitchell, H Bleecker, ER Castro, M Wenzel, S Erzurum, SC Fitzpatrick, AM Teague, WG Jarjour, N Moore, WC Sumino, K Simeone, S Ratanamaneechat, S Penugonda, M Gaston, B Ross, TM Sigelman, S Schiepan, JR Zaccaro, DJ Crevar, CJ Carter, DM Togias, A AF Busse, William W. Peters, Stephen P. Fenton, Matthew J. Mitchell, Herman Bleecker, Eugene R. Castro, Mario Wenzel, Sally Erzurum, Serpil C. Fitzpatrick, Anne M. Teague, W. Gerald Jarjour, Nizar Moore, Wendy C. Sumino, Kaharu Simeone, Scott Ratanamaneechat, Suphagaphan Penugonda, Madhuri Gaston, Benjamin Ross, Ted M. Sigelman, Steve Schiepan, Joella R. Zaccaro, Daniel J. Crevar, Corey J. Carter, Donald M. Togias, Alkis TI Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE H1N1; asthma; influenza; vaccine; seroprotection; severe asthma ID CHILDREN; SAFETY; ADULTS; TRIAL; AGE; IMMUNOGENICITY; ADOLESCENTS; EFFICACY; OLDER AB Background: Asthma was the most common comorbidity of patients hospitalized with 2009 H1N1 influenza. Objective: We sought to assess the immunogenicity and safety of an unadjuvanted, inactivated 2009 H1N1 vaccine in patients with severe versus mild-to-moderate asthma. Methods: We conducted an open-label study involving 390 participants (age, 12-79 years) enrolled in October-November 2009. Severe asthma was defined as need for 880 mu g/d or more of inhaled fluticasone equivalent, systemic corticosteroids, or both. Within each severity group, participants were randomized to receive intramuscularly 15 or 30 mu g of 2009 H1N1 vaccine twice 21 days apart. Immunogenicity end points were seroprotection (hemagglutination inhibition assay titer >= 40) and seroconversion (4-fold or greater titer increase). Safety was assessed through local and systemic reactogenicity, asthma exacerbations, and pulmonary function. Results: In patients with mild-to-moderate asthma (n =217), the 2009 H1N1 vaccine provided equal seroprotection 21 days after the first immunization at the 15-mu g (90.6%; 95% CI, 83.5% to 95.4%) and 30-mu g (95.3%; 95% CI, 89.4% to 98.5%) doses. In patients with severe asthma (n = 173), seroprotection 21 days after the first immunization was 77.9% (95% CI, 67.7% to 86.1%) and 94.1% (95% CI, 86.8% to 98.1%) at the 15- and 30-mg doses, respectively (P = .004). The second vaccination did not provide further increases in seroprotection. Participants with severe asthma who are older than 60 years showed the lowest seroprotection (44.4% at day 21) with the 15-mg dose but had adequate seroprotection with 30 mg. The 2 dose groups did not differ in seroconversion rates. There were no safety concerns. Conclusion: Monovalent inactivated 2009 H1N1 pandemic influenza vaccine was safe and provided overall seroprotection as a surrogate of efficacy. In patients older than 60 years with severe asthma, a 30-mg dose might be more appropriate. (J Allergy Clin Immunol 2011;127:130-7.) C1 [Busse, William W.; Jarjour, Nizar] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Peters, Stephen P.; Bleecker, Eugene R.; Moore, Wendy C.] Wake Forest Univ, Hlth Sci Ctr Genom & Personalized Med Res, Winston Salem, NC 27109 USA. [Fenton, Matthew J.; Sigelman, Steve; Togias, Alkis] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Castro, Mario; Sumino, Kaharu] Washington Univ, Sch Med, St Louis, MO USA. [Mitchell, Herman; Schiepan, Joella R.; Zaccaro, Daniel J.] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [Wenzel, Sally; Simeone, Scott] Univ Pittsburgh, Asthma Inst, Pittsburgh, PA USA. [Erzurum, Serpil C.; Ratanamaneechat, Suphagaphan] Cleveland Clin, Cleveland, OH 44106 USA. [Fitzpatrick, Anne M.; Penugonda, Madhuri] Emory Univ, Atlanta, GA 30322 USA. [Teague, W. Gerald; Gaston, Benjamin] Univ Virginia, Childrens Hosp, Div Resp Med, Charlottesville, VA USA. [Ross, Ted M.; Crevar, Corey J.; Carter, Donald M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA. RP Busse, WW (reprint author), Univ Wisconsin Hosp & Clin, K4-910 CSC,MC 9988,600 Highland Ave, Madison, WI 53792 USA. EM wwb@medicine.wisc.edu FU US National Institutes of Health (NIH) through National Institute of Allergy and Infectious Diseases (NIAID) [3 R01 HL069116-09S1]; Rho, Inc; NIAID [NO1-AI-25482]; NIH [RO1 HL69170, HL081064]; National Center for Research Resources [1UL1RR024989, UL1RR025008]; Novartis; AstraZeneca; GlaxoSmithKline; MedImmune; Ception; National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID); NIH/National Heart, Lung, and Blood Institute (NHLBI); Elsevier; NIH; Genentech FX Funding for this study was provided by the US National Institutes of Health (NIH) through a supplement contribution from the National Institute of Allergy and Infectious Diseases (NIAID) to the National Heart, Lung, and Blood Institute (NHLBI)-funded grant 3 R01 HL069116-09S1. Rho, Inc, the Data and Statistical Coordinating Center for this study, was funded by NIAID contract number NO1-AI-25482. Additional funds were provided by the NIH Research Project grants RO1 HL69170 and HL081064 and by the National Center for Research Resources under grants 1UL1RR024989 and UL1RR025008. NIAID and NHLBI scientists and project managers were involved in the design of the study and the writing of the protocol, as well as in study medical monitoring, data analysis, and manuscript preparation. Vaccine was purchased from Novartis Vaccines and Diagnostics Ltd by the US Government BioMedical Advanced Research and Development Authority (BARDA), which coordinated the 2009 H1N1 pandemic influenza vaccination in the United Sates. BARDA had no other role in this study.; W. W. Busse is on advisory boards for Altair, Amgen, Centocor, GlaxoSmithKline, Merck, Pfizer, Wyeth, and Johnson & Johnson; has consultant arrangements with AstraZeneca, Boehringer Ingelheim, Novartis, TEVA, and GlaxoSmithKline; is a speaker for Merck; and receives research support from Novartis, AstraZeneca, GlaxoSmithKline, MedImmune, Ception, the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), and the NIH/National Heart, Lung, and Blood Institute (NHLBI). S. P. Peters receives research support from the NIH/NHLBI and Novartis. H. Mitchell receives research support from the NIH. E. R. Bleecker receives research support from the NIH/NHLBI and Novartis. M. Castro has consultant arrangements with Electrocore, NKTT, Schering-Plough, Asthmatx, and Cephalon; is on the advisory board for Genentech; is a speaker for AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, and GlaxoSmithKline; has received institutional grant support from Asthmatx, Amgen, Ception, Genentech, MedImmune, Merck, Novartis, the NIH, and GlaxoSmithKline; has received royalties from Elsevier; and has received research support from the NIH. W. G. Teague is a speaker for Merck and receives research support from the NIH. N. Jarjour has consultant arrangements with Asthmatx and Genentech; receives research support from GlaxoSmithKline, MedImmune, and Genentech; and receives honoraria from Merck. W. C. Moore receives research support from the NHLBI. K. Sumino receives research support from the NIH and the VA. B. Gaston receives research support from the NIH. J. R. Schiepan receives research support from the NIH. The rest of the authors have declared that they have no conflict of interest. NR 32 TC 22 Z9 22 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2011 VL 127 IS 1 BP 130 EP U215 DI 10.1016/j.jaci.2010.11.014 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 702SY UT WOS:000285917300019 PM 21145578 ER PT J AU Haberg, SE London, SJ Nafstad, P Nilsen, RM Ueland, PM Vollset, SE Nystad, W AF Haberg, Siri E. London, Stephanie J. Nafstad, Per Nilsen, Roy M. Ueland, Per Magne Vollset, Stein Emil Nystad, Wenche TI Maternal folate levels in pregnancy and asthma in children at age 3 years SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID NEURAL-TUBE DEFECTS; FOLIC-ACID; SUPPLEMENTATION; PREVENTION; VITAMIN; COHORT C1 [Haberg, Siri E.; Nafstad, Per; Nystad, Wenche] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [London, Stephanie J.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Nafstad, Per] Univ Oslo, Dept Gen Practice & Community Med, Fac Med, N-0316 Oslo, Norway. [Nilsen, Roy M.] Haukeland Hosp, Clin Res Ctr, N-5021 Bergen, Norway. [Ueland, Per Magne] Haukeland Hosp, Lab Clin Biochem, N-5021 Bergen, Norway. [Ueland, Per Magne] Univ Bergen, Pharmacol Sect, Inst Med, N-5020 Bergen, Norway. [Vollset, Stein Emil] Norwegian Inst Publ Hlth, Bergen, Norway. RP Haberg, SE (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. EM siri.haberg@fhi.no RI Ueland, Per/C-7340-2013; OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES049019-12]; NIEHS NIH HHS [N01-ES-85433, N01ES85433, Z01 ES044008, Z01 ES049019]; NINDS NIH HHS [1 U01 NS047537-01, U01 NS047537] NR 8 TC 52 Z9 54 U1 1 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2011 VL 127 IS 1 BP 262 EP 264 DI 10.1016/j.jaci.2010.10.004 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 702SY UT WOS:000285917300037 PM 21094522 ER PT J AU Ge, AXY Ryan, ME Holland, SM Freeman, AF Anderson, VL Wang, F Fleshman, JW AF Ge, Adeline X. Y. Ryan, Mary E. Holland, Steven M. Freeman, Alexandra F. Anderson, Victoria L. Wang, Fei Fleshman, Jim W. TI Acupuncture for Symptom Management in Patients with Hyper-IgE (Job's) Syndrome SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; RECURRENT-INFECTION; MUTATIONS; HEADACHE; FATIGUE; PAIN; MECHANISM; MIGRAINE; CHILDREN; DOCK8 AB Objectives: The objective of this study was to investigate the effects of acupuncture treatment for symptom management in patients with hyper-immunoglobulin E (IgE) syndrome (HIES). Design: This was a retrospective case series. Setting/location: The study was conducted at the The Clinical Research Center of the National Institutes of Health. Subjects: There were 8 adult patients with HIES ages 23-56 with varying symptoms in the study. Intervention: Acupuncture treatments were given from May 29, 2001 to February 17, 2009. Outcome measures: Acupuncture treatment efficacy was measured and evaluated using a 0-10 assessment instrument pre- and post-treatment. Results: The 8 patients with HIES suffered from a wide variety of symptoms related to the disease. Acupuncture treatments uniformly decreased the self-reported severity of symptoms. Conclusions: This case series demonstrates that acupuncture is a clinically useful and safe therapy for symptom management in patients with HIES. C1 [Ge, Adeline X. Y.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Ryan, Mary E.; Fleshman, Jim W.] NIH, NIH Lib, Bethesda, MD 20892 USA. [Ryan, Mary E.; Fleshman, Jim W.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Holland, Steven M.; Freeman, Alexandra F.; Anderson, Victoria L.] NIAID, NIH, Bethesda, MD 20892 USA. [Wang, Fei] KAI Res Inc, Rockville, MD USA. RP Ge, AXY (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10,Room 4-1741,9000 Rockville Pike, Bethesda, MD 20892 USA. EM age@mail.nih.gov FU National Center for Complementary and Alternative Medicine (NCCAM), NIH FX This study was supported by the Intramural Research Program of National Center for Complementary and Alternative Medicine (NCCAM), NIH. We thank Josephine Briggs, MD, NCCAM Director; Robert Nussenblatt, MD, Scientific and Clinical Director, Division of Intramural Research, NCCAM; David Henderson, MD, Director for Clinical Care and his staff; the Medical Record Department of NIH; Chris Thomsen, Catherine Meyers, MD, Laura Lee Johnson, PhD, Chingyi Shieh, PhD, Michelle Hendery, Belinda Davis, Deborah Hayes of NIH; and Celester Crouse, Madiha Khan, Stephanie Millin, Kimberly Viens, Uma Ragunathan, Megan Schmidt, and Sarah Macht of KAI Research, Inc. Their wonderful support made this publication possible. NR 45 TC 0 Z9 0 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JAN PY 2011 VL 17 IS 1 BP 71 EP 76 DI 10.1089/acm.2010.0264 PG 6 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 711MA UT WOS:000286594500014 PM 21208131 ER PT J AU Araujo, JA Greig, NH Ingram, DK Sandin, J de Rivera, C Milgram, NW AF Araujo, Joseph A. Greig, Nigel H. Ingram, Donald K. Sandin, Johan de Rivera, Christina Milgram, Norton W. TI Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cholinesterase inhibitor; dog; donepezil; learning; memory; phenserine ID AMYLOID PRECURSOR PROTEIN; 14-UNIT T-MAZE; ALZHEIMERS-DISEASE; CANINE MODEL; SENILE-DEMENTIA; WORKING-MEMORY; CHOLINERGIC HYPOTHESIS; COGNITIVE DYSFUNCTION; ACETYLCHOLINESTERASE INHIBITOR; RESPONSIVE ELEMENT AB Similar to patients with Alzheimer's disease (AD), dogs exhibit age-dependent cognitive decline, amyloid-beta (A beta) pathology, and evidence of cholinergic hypofunction. The present study sought to further investigate the role of cholinergic hypofunction in the canine model by examining the effect of the cholinesterase inhibitors phenserine and donepezil on performance of two tasks, a delayed non-matching-to-position task (DNMP) designed to assess working memory, and an oddity discrimination learning task designed to assess complex learning, in aged dogs. Phenserine (0.5 mg/kg; PO) significantly improved performance on the DNMP at the longest delay compared to wash-out and partially attenuated scopolamine-induced deficits (15 mu g/kg; SC). Phenserine also improved learning on a difficult version of an oddity discrimination task compared to placebo, but had no effect on an easier version. We also examined the effects of three doses of donepezil (0.75, 1.5, and 6 mg/kg; PO) on performance of the DNMP. Similar to the results with phenserine, 1.5 mg/kg of donepezil improved performance at the longest delay compared to baseline and wash-out, indicative of memory enhancement. These results further extend the findings of cholinergic hypofunction in aged dogs and provide pharmacological validation of the canine model with a cholinesterase inhibitor approved for use in AD. Collectively, these studies support utilizing the aged dog in future screening of therapeutics for AD, as well as for investigating the links among cholinergic function, A beta pathology, and cognitive decline. C1 [Araujo, Joseph A.] InterVivo Solut Inc, Toronto, ON M5A 4K2, Canada. [Araujo, Joseph A.; de Rivera, Christina; Milgram, Norton W.] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. [Araujo, Joseph A.; de Rivera, Christina; Milgram, Norton W.] CanCog Technol Inc, Toronto, ON, Canada. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Baltimore, MD 21224 USA. [Ingram, Donald K.] LSU Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. [Sandin, Johan] AstraZeneca R&D Sodertalje, Dept Neurosci, Sodertalje, Sweden. [Milgram, Norton W.] Univ Toronto, Div Life Sci, Toronto, ON, Canada. RP Araujo, JA (reprint author), InterVivo Solut Inc, 120 Carlton St,Suite 203, Toronto, ON M5A 4K2, Canada. EM josepha@intervivosolutions.com OI Sandin, Johan/0000-0001-8385-456X FU Natural Sciences and Engineering Research Council of Canada [A7659]; National Institute on Aging, National Institutes of Health, USA; CanCog Technologies, Inc. FX The Natural Sciences and Engineering Research Council of Canada supported this work with Grant A7659 to NWM, and postgraduate scholarships to J.A.A. Special thanks are extended to the University of Toronto's Division of Comparative Medicine's staff. This work was also supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA and research and development funding from CanCog Technologies, Inc. JAA, CD and NWM served as shareholders and/or employees of CanCog. JAA is an employee of Inter-Vivo Solutions. NR 96 TC 12 Z9 12 U1 1 U2 12 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 IS 1 BP 143 EP 155 DI 10.3233/JAD-2011-110005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 812XG UT WOS:000294326100013 PM 21593569 ER PT J AU Peuralinna, T Tanskanen, M Makela, M Polvikoski, T Paetau, A Kalimo, H Sulkava, R Hardy, J Lai, SL Arepalli, S Hernandez, D Traynor, BJ Singleton, A Tienari, PJ Myllykangas, L AF Peuralinna, Terhi Tanskanen, Maarit Makela, Mira Polvikoski, Tuomo Paetau, Anders Kalimo, Hannu Sulkava, Raimo Hardy, John Lai, Shiao-Lin Arepalli, Sampath Hernandez, Dena Traynor, Bryan J. Singleton, Andrew Tienari, Pentti J. Myllykangas, Liisa TI APOE and A beta PP Gene Variation in Cortical and Cerebrovascular Amyloid-beta Pathology and Alzheimer's Disease: A Population-Based Analysis SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta deposition; A beta PP; APOE; cerebral amyloid angiopathy; neuropathology ID GENOME-WIDE ASSOCIATION; APP GENE; APOLIPOPROTEIN-E; PROMOTER POLYMORPHISMS; IDENTIFIES VARIANTS; DOWNS-SYNDROME; TAU-PATHOLOGY; SILVER STAIN; PROTEIN; PRECURSOR AB Cortical and cerebrovascular amyloid-beta (A beta) deposition is a hallmark of Alzheimer's disease (AD), but also occurs in elderly people not affected by dementia. The apolipoprotein E (APOE) epsilon 4 is a major genetic modulator of A beta deposition and AD risk. Variants of the amyloid-beta protein precursor (A beta PP) gene have been reported to contribute to AD and cerebral amyloid angiopathy (CAA). We analyzed the role of APOE and A beta PP variants in cortical and cerebrovascular A beta deposition, and neuropathologically verified AD (based on modified NIA-RI criteria) in a population-based autopsy sample of Finns aged >= 85 years (Vantaa85 + Study; n = 282). Our updated analysis of APOE showed strong associations of the epsilon 4 allele with cortical (p = 4.91x10(-17)) and cerebrovascular (p = 9.87x10(-11)) A beta deposition as well as with NIA-RI AD (p = 1.62x10(-8)). We also analyzed 60 single nucleotide polymorphisms (SNPs) at the A beta PP locus. In single SNP or haplotype analyses there were no statistically significant A beta PP locus associations with cortical or cerebrovascular A beta deposition or with NIA-RI AD. We sequenced the promoter of the A beta PP gene in 40 subjects with very high A beta deposition, but none of these subjects had any of the previously reported or novel AD-associated mutations. These results suggest that cortical and cerebrovascular A beta depositions are useful quantitative traits for genetic studies, as highlighted by the strong associations with the APOE epsilon 4 variant. Promoter mutations or common allelic variation in the A beta PP gene do not have a major contribution to cortical or cerebrovascular A beta deposition, or very late-onset AD in this Finnish population based study. C1 [Peuralinna, Terhi; Tienari, Pentti J.] Univ Helsinki, Res Program Mol Neurol Biomed Helsinki, Helsinki, Finland. [Peuralinna, Terhi; Myllykangas, Liisa] Folkhalsan Inst Genet, Helsinki, Finland. [Tanskanen, Maarit; Makela, Mira; Paetau, Anders; Kalimo, Hannu; Myllykangas, Liisa] Univ Helsinki & HUSLAB, Haartman Inst, Dept Pathol, Helsinki, Finland. [Polvikoski, Tuomo] Newcastle Univ, Inst Aging & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Sulkava, Raimo] Univ Kuopio, Dept Publ Hlth & Gen Practice, Div Geriatr, FIN-70211 Kuopio, Finland. [Sulkava, Raimo] Univ Kuopio, Ctr Hosp, FIN-70211 Kuopio, Finland. [Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Lai, Shiao-Lin; Traynor, Bryan J.] NIA, Neuromusc Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Arepalli, Sampath; Hernandez, Dena; Singleton, Andrew] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Tienari, Pentti J.] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland. RP Myllykangas, L (reprint author), Univ Helsinki, Dept Pathol, Haartman Inst & HUSLAB, POB 21, FIN-00014 Helsinki, Finland. EM liisa.myllykangas@helsinki.fi RI Tienari, Pentti/A-4893-2012; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010 FU National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000950-07]; Microsoft Research Foundation; ALS foundation; Graduate School of Molecular Biology and Biotechnology of the University of Helsinki; Folkhalsan Research Foundation; Helsinki University Central Hospital FX This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project number Z01 AG000950-07), by Microsoft Research Foundation, ALS foundation, Graduate School of Molecular Biology and Biotechnology of the University of Helsinki, Folkhalsan Research Foundation and the Helsinki University Central Hospital. NR 47 TC 8 Z9 8 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 IS 2 BP 377 EP 385 DI 10.3233/JAD-2011-102049 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 818OR UT WOS:000294763100015 PM 21654062 ER PT J AU Chen, KH Reese, EA Kim, HW Rapoport, SI Rao, JS AF Chen, Kevin H. Reese, Edmund A. Kim, Hyung-Wook Rapoport, Stanley I. Rao, Jagadeesh S. TI Disturbed Neurotransmitter Transporter Expression in Alzheimer's Disease Brain (Retracted article. See vol. 55, pg. 445, 2016) SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article; Retracted Publication DE Alzheimer's disease; catechol O-methyltransferase; COMT; dopamine transporter; excitatory amino acid; frontal cortex; serotonin; vesicular acetylcholine; vesicular glutamate transporter ID VESICULAR ACETYLCHOLINE TRANSPORTER; POSITRON-EMISSION-TOMOGRAPHY; MILD COGNITIVE IMPAIRMENT; MESSENGER-RNA EXPRESSION; GLUTAMATE TRANSPORTERS; FRONTAL-CORTEX; RAT-BRAIN; NEURODEGENERATIVE DISEASES; SYNAPTIC PLASTICITY; ARACHIDONIC-ACID AB Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory loss and behavioral and psychological symptoms of dementia. An imbalance of different neurotransmitters-glutamate, acetylcholine, dopamine, and serotonin-has been proposed as the neurobiological basis of behavioral symptoms in AD. The molecular changes associated with neurotransmission imbalance in AD are not clear. We hypothesized that altered reuptake of neurotransmitters by vesicular glutamate transporters (VGLUTs), excitatory amino acid transporters (EAATs), the vesicular acetylcholine transporter (VAChT), the serotonin reuptake transporter (SERT), or the dopamine reuptake transporter (DAT) are involved in the neurotransmission imbalance in AD. We tested this hypothesis by examining protein and mRNA levels of these transporters in postmortem prefrontal cortex from 10 AD patients and 10 matched non-AD controls. Compared with controls, protein and mRNA levels of VGLUTs, EAAT1-3, VAChT, and SERT were reduced significantly in AD. Expression of DAT and catechol O-methyltransferase was unchanged. Reduced VGLUTs and EAATs may contribute to an alteration in glutamatergic recycling, and reduced SERT could exacerbate depressive symptoms in AD. The reduced VAChT expression could contribute to the recognized cholinergic deficit in AD. Altered neurotransmitter transporters could contribute to the pathophysiology of AD and are potential targets for therapy. C1 [Chen, Kevin H.; Reese, Edmund A.; Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1S-126, Bethesda, MD 20892 USA. EM jrao@grc.nia.nih.gov FU Harvard Brain Bank, Boston, MA [R24MH068855]; National Institute on Aging, National Institutes of Health FX We thank the Harvard Brain Bank, Boston, MA, for providing the postmortem brain samples under PHS grant number R24MH068855. This research was entirely supported by the Intramural Research Programs of the National Institute on Aging, National Institutes of Health. NR 74 TC 53 Z9 56 U1 2 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 26 IS 4 BP 755 EP 766 DI 10.3233/JAD-2011-110002 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 832XE UT WOS:000295843000013 PM 21743130 ER PT J AU Broer, L Ikram, A Schuur, M DeStefano, AL Bis, JC Liu, F Rivadeneira, F Uitterlinden, AG Beiser, AS Longstreth, WT Hofman, A Aulchenko, Y Seshadri, S Fitzpatrick, AL Oostra, BA Breteler, MMB van Duijn, CM AF Broer, Linda Ikram, Arfan Schuur, Maaike DeStefano, Anita L. Bis, Joshua C. Liu, Fan Rivadeneira, Fernando Uitterlinden, Andre G. Beiser, Alexa S. Longstreth, William T. Hofman, Albert Aulchenko, Yurii Seshadri, Sudha Fitzpatrick, Annette L. Oostra, Ben A. Breteler, Monique M. B. van Duijn, Cornelia M. TI Association of HSP70 and its Co-Chaperones with Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; genetic association studies; heat-shock proteins; prefoldin ID GENOME-WIDE ASSOCIATION; HEAT-SHOCK PROTEINS; NEURODEGENERATIVE DISEASES; CARDIOVASCULAR HEALTH; MOLECULAR CHAPERONES; PATHWAY ANALYSIS; MENTAL STATE; FRAMINGHAM; DEMENTIA; FAMILY AB The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer's disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of 462 patients and 5238 unaffected participants derived from the Rotterdam Study, a population-based study including 7983 persons aged 55 years and older. We genotyped a total of 12,053 Single Nucleotide Polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. Replication was performed in two independent cohort studies, the Framingham Heart study (FHS; n = 806) and Cardiovascular Health Study (CHS; n = 2150). When adjusting for multiple testing, we found a small but consistent, though not significant effect of rs12118313 located 32 kb from PFDN2, with an OR of 1.19 (p-value from meta-analysis = 0.003). However this SNP was in the intron of another gene, suggesting it is unlikely this SNP reflects the effect of PFDN2. In a formal pathway analysis we found nominally significant evidence for an association of BAG, DNAJA and prefoldin with AD. These findings corroborate with those of a study of 2032 AD patients and 5328 controls, in which several members of the prefoldin family showed evidence for association to AD. Our study did not reveal evidence for a genetic variant if the HSP70 family with a major effect on AD. However, our findings of the single SNP analysis and pathway analysis suggest that multiple genetic variants in prefoldin are associated with AD. C1 [Broer, Linda; Ikram, Arfan; Liu, Fan; Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert; Aulchenko, Yurii; Breteler, Monique M. B.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Schuur, Maaike] Erasmus MC, Dept Neurol, Rotterdam, Netherlands. [DeStefano, Anita L.; Beiser, Alexa S.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [DeStefano, Anita L.; Beiser, Alexa S.; Seshadri, Sudha] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [DeStefano, Anita L.; Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Resarch Unit, Seattle, WA 98195 USA. [Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA. [Longstreth, William T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, William T.; Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.] NCHA, NGI, Rotterdam, Netherlands. RP van Duijn, CM (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, Dr Molewaterpl 50,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM c.vanduijn@erasmusmc.nl RI Aulchenko, Yurii/M-8270-2013; Breteler, Monique /J-5058-2014; Rivadeneira, Fernando/O-5385-2015; Liu, Fan/B-8833-2013; OI Aulchenko, Yurii/0000-0002-7899-1575; Rivadeneira, Fernando/0000-0001-9435-9441; Liu, Fan/0000-0001-9241-8161; Ikram, Mohammad Arfan/0000-0003-0372-8585 FU Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organisation for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission; Municipality of Rotterdam; Alzheimer Association [IIRG-05-14359]; Hersenstichting Nederland; Internationale Stichting Alzheimer Onderzoek (ISAO); National Heart, Lung, and Blood Institute [01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL087652, N01-HC-25195]; National Institute of Neurological Disorders and Stroke; National Institute on Aging [AG15928, AG20098, AG05133]; National Center for Research Resources [M01RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR); Affymetrix, Inc [N02-HL-6-4278]; Department of Medicine at Boston University School of Medicine and Boston Medical Center; National Institute of Neurological Disorders and Stroke [NS17950]; National Institute of Aging [AG08122, AG16495, AG033193, AG031287, P30AG013846, AG025259] FX RS1. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database, and Karol Estrada and Maksim V. Struchalin for their support in creation and analysis of imputed data.; The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organisation for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists.; Additional funding was obtained from the Alzheimer Association IIRG-05-14359, Hersenstichting Nederland and Internationale Stichting Alzheimer Onderzoek (ISAO).; CHS. The research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke and grants AG15928 and AG20098, and AG05133 from the National Institute on Aging. DNA handling and genotyping was supported in part by National Center for Research Resources grant M01RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core, National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center, and the Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR). A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm.; FHS. From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This study was also supported by grants from the National Institute of Neurological Disorders and Stroke (NS17950) and the National Institute of Aging (AG08122, AG16495, AG033193, AG031287, P30AG013846, and AG025259). NR 44 TC 8 Z9 8 U1 1 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 25 IS 1 BP 93 EP 102 DI 10.3233/JAD-2011-101560 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 800QE UT WOS:000293377700010 PM 21403392 ER PT J AU Gleichmann, M Chow, VW Mattson, MP AF Gleichmann, Marc Chow, Vivian W. Mattson, Mark P. TI Homeostatic Disinhibition in the Aging Brain and Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cognitive reserve; disinhibition; GABA; interneuron; neuronal activity ID INITIATIVE PROGRESS REPORT; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA OLIGOMERS; LONG-TERM POTENTIATION; NEUROTROPHIC FACTOR; BEHAVIORAL ENRICHMENT; SYNAPTIC PLASTICITY; GABA CONCENTRATION; TRANSGENIC MODEL; GENE-EXPRESSION AB In this article, we propose that impaired efficiency of glutamatergic synaptic transmission and a compensatory reduction in inhibitory neurotransmission, a process called homeostatic dishinhibition, occurs in the aging brain and more dramatically in Alzheimer's disease (AD). Homeostatic disinhibition may help understand certain features of the aging brain and AD, including: 1) the increased risk for epileptic seizures, especially in the early phase of the disease; 2) the reduced ability to generate gamma-oscillations; and 3) the increase in neuronal activity as measured by functional MRI. Homeostatic disinhibition may be the major mechanism that activates cognitive reserve. Modulating neuronal activity may therefore be a viable therapeutic strategy in AD that can complement existing anti-amyloid strategies. Specifically, enhancing endogenous glutamatergic synaptic transmission through increased co-agonist signaling or through positive allosteric modulation of metabotropic glutamatergic receptors appears as an attractive strategy. Alternatively, further reduction of GABAergic signaling may work as well, although care has to be taken to prevent epileptic seizures. C1 [Gleichmann, Marc; Mattson, Mark P.] NIA, Neurosci Lab, Baltimore, MD 21224 USA. [Chow, Vivian W.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Mattson, MP (reprint author), Biomed Res Ctr, 5th Floor,251 Bayview Blvd, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [ZIA AG000312-11, ZIA AG000313-10]; NIA NIH HHS [T32 AG027668] NR 85 TC 16 Z9 17 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 24 IS 1 BP 15 EP 24 DI 10.3233/JAD-2010-101674 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 741XF UT WOS:000288899200004 PM 21187584 ER PT J AU Chigurupati, S Madan, M Okun, E Wei, ZL Pattisapu, JV Mughal, MR Mattson, MP Chan, SL AF Chigurupati, Srinivasulu Madan, Meenu Okun, Eitan Wei, Zelan Pattisapu, Jogi V. Mughal, Mohamed R. Mattson, Mark P. Chan, Sic L. TI Evidence for Altered Numb Isoform Levels in Alzheimer's Disease Patients and a Triple Transgenic Mouse Model SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta peptide; endocytosis; endosomes; protein trafficking ID AMYLOID-PRECURSOR-PROTEIN; MAMMALIAN NUMB; BETA-PEPTIDE; INTRACELLULAR DOMAIN; ASYMMETRIC DIVISION; BINDING-SPECIFICITY; ENDOCYTIC PROTEIN; ADAPTER PROTEIN; CELL FATE; IN-VIVO AB The cell fate determinant Numb exists in four alternatively spliced variants that differ in the length of their PTB (phosphotyrosine-binding domain, either lacking or containing an 11 amino acid insertion) and PRR (proline-rich region, either lacking or containing a 48 amino acid insertion). We previously reported that Numb switches from isoforms containing the PTB insertion to isoforms lacking this insertion in neural cultures subjected to stress induced by trophic factor withdrawal. The switch in Numb isoforms enhances the generation of amyloid-beta peptide (A beta), the principle component of senile plaques in Alzheimer's disease (AD). Here we examine the expression of the Numb isoforms in brains from AD patients and triple transgenic (3xTg) AD mice. We found that levels of the Numb isoforms lacking the PTB insertion are significantly elevated in the parietal cortex but not in the cerebellum of AD patients when compared to control subjects. Levels of Numb isoforms lacking the PTB insertion were also elevated in the cortex but not cerebellum of 12 month-old 3xTg AD mice with A beta deposits compared to younger 3xTg-AD mice and to non-transgenic mice. Exposure of cultured neurons to A beta resulted in an increase in the levels of Numb isoforms lacking the PTB domain, consistent with a role for A beta in the aberrant expression of Numb in vulnerable brain regions of AD patients and mice. Collectively, the data show that altered expression of Numb isoforms in vulnerable neurons occurs during AD pathogenesis and suggest a role for Numb in the disease process. C1 [Chigurupati, Srinivasulu; Madan, Meenu; Wei, Zelan; Pattisapu, Jogi V.; Chan, Sic L.] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Orlando, FL 32816 USA. [Chigurupati, Srinivasulu; Okun, Eitan; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Chan, SL (reprint author), Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, 4000 Cent Florida Blvd, Orlando, FL 32816 USA. EM schan@mail.ucf.edu RI Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 FU American Heart Association; National Institute on Aging Intramural Research Program of the NIH FX Supported in part by an American Heart Association Beginning Grant-in-Aid (to S.L.C). and the National Institute on Aging Intramural Research Program of the NIH. NR 49 TC 5 Z9 6 U1 0 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 24 IS 2 BP 349 EP 361 DI 10.3233/JAD-2010-101797 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 747WS UT WOS:000289352400014 PM 21258150 ER PT J AU Igarashi, M Ma, KZ Gao, F Kim, HW Rapoport, SI Rao, JS AF Igarashi, Miki Ma, Kaizong Gao, Fei Kim, Hyung-Wook Rapoport, Stanley I. Rao, Jagadeesh S. TI Disturbed Choline Plasmalogen and Phospholipid Fatty Acid Concentrations in Alzheimer's Disease Prefrontal Cortex SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; arachidonic acid; brain; cholesteryl ester; docosahexaenoic acid; lipid; phospholipid; plasmalogen; postmortem ID DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; HUMAN BRAIN; RAT-BRAIN; NEURODEGENERATIVE DISEASES; MEMBRANE INSTABILITY; COGNITIVE IMPAIRMENT; MASS-SPECTROMETRY; DIFFERENT REGIONS; LIPID-COMPOSITION AB Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by brain deposition of senile (neuritic) plaques containing amyloid-beta, neurofibrillary tangles, synaptic loss, neuroinflammation, and overexpression of arachidonic acid (AA, 20:4n-6) metabolizing enzymes. Lipid concentration changes have been reported in different brain regions, but often partially or as a percent of the total concentration. In this study, we measured absolute concentrations (per gram wet weight) of a wide range of lipids in postmortem prefrontal cortex (Brodmann area 9) from 10 AD patients and 9 non-AD controls. Mean total brain lipid, phospholipid, cholesterol, and triglyceride concentrations did not differ significantly between AD and controls. There was a significant 73% decrease in choline plasmalogen, but no difference in other measured phospholipids. Fatty acid concentrations in total phospholipid did not differ from control. However, docosahexaenoic acid (DHA, 22:6n-3) was reduced in ethanolamine glycerophospholipid and choline glycerophospholipid, but increased in phosphatidylinositol. AA was reduced in choline glycerophospholipid, but increased in phosphatidylinositol, while docosatetraenoic acid (22:4n-6), an AA elongation product, was reduced in total brain lipid, cholesteryl ester and triglyceride. These lipid changes, which suggest extensive membrane remodeling, may contribute to membrane instability and synaptic loss in AD and reflect neuroinflammation. C1 [Igarashi, Miki; Ma, Kaizong; Gao, Fei; Kim, Hyung-Wook; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Igarashi, M (reprint author), Univ Calif Irvine, Irvine, CA 92697 USA. EM miki.i@uci.edu FU Harvard Brain Bank, Boston, MA [R24MH068855]; National Institute on Aging, National Institutes of Health, Bethesda, MD, USA FX We thank the Harvard Brain Bank, Boston, MA for providing the post-mortem brain samples under PHS grant number R24MH068855. This research was supported entirely by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. We thank Dr. Ameer Taha for his useful comments. NR 70 TC 55 Z9 58 U1 5 U2 18 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 24 IS 3 BP 507 EP 517 DI 10.3233/JAD-2011-101608 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 789EN UT WOS:000292496900008 PM 21297269 ER PT J AU Marengoni, A Fratiglioni, L Bandinelli, S Ferrucci, L AF Marengoni, Alessandra Fratiglioni, Laura Bandinelli, Stefania Ferrucci, Luigi TI Socioeconomic Status During Lifetime and Cognitive Impairment No-Dementia in Late Life: The Population-Based Aging in the Chianti Area (InCHIANTI) Study SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognitive impairment no-dementia; epidemiology; education; finances; occupation; socioeconomic status ID VASCULAR RISK-FACTORS; KUNGSHOLMEN PROJECT; ELDERLY POPULATION; OLDER-PEOPLE; FOLLOW-UP; PREVALENCE; AGE; EDUCATION; HEALTH; CIND AB Thousand and twelve dementia-free elderly (60-98 years old) enrolled in the InChianti Study (Italy) were evaluated at baseline (1998-2000) and at 3-year follow-up (2001-2003) with the aim of analyzing the association of lifetime socioeconomic status (SES) with prevalent and incident cognitive impairment no-dementia (CIND). SES was defined from information on formal education, longest held occupation, and financial conditions through life. CIND was defined as age-adjusted Mini-Mental State Examination score one standard deviation below the baseline mean score of participants without dementia. Logistic regression and Cox proportional-hazards models were used to estimate the association of SES with CIND. Demographics, occupation characteristics (i.e., job stress and physical demand), cardiovascular diseases, diabetes, apolipoprotein E (APOE) genotype, smoking, alcohol consumption, depressive symptoms, and C-reactive protein were considered potential confounders. Prevalence of CIND was 17.7%. In the fully adjusted model, low education (OR = 2.1; 95% confidence intervals, CI = 1.4 to 3.2) was associated with prevalent CIND. Incidence rate of CIND was 66.0 per 1000 person-years. Low education (HR = 1.7; 95% CI = 1.04 to 2.6) and manual occupation (HR = 1.9; 95% CI = 1.0 to 3.6) were associated with incident CIND. Among covariates, high job-related physical demand was associated with both prevalent and incident CIND (OR = 1.6; 95% CI = 1.1 to 2.4 and HR = 1.5; 95% CI = 1.0 to 2.3). After stratification for education, manual occupation was still associated with CIND among participants with high education (HR = 2.2; 95% CI = 1.2 to 4.3 versus HR = 1.4; 95% CI = 0.2 to 10.4 among those with low education). Proxy markers of lifetime SES (low education, manual occupation and high physical demand) are cross-sectional correlates of CIND and predict incident CIND over a three-year follow-up. C1 [Marengoni, Alessandra] Univ Brescia, Dept Med & Surg Sci, I-25123 Brescia, Italy. [Marengoni, Alessandra; Fratiglioni, Laura] Stockholm Univ, Karolinska Inst, Dept Neurobiol Care Sci & Soc, Aging Res Ctr, S-10691 Stockholm, Sweden. [Fratiglioni, Laura] Stockholm Gerontol Res Ctr, Stockholm, Sweden. [Bandinelli, Stefania] ASF Geriatr Rehabil, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA. RP Marengoni, A (reprint author), Univ Brescia, Dept Med & Surg Sci, Piazzale Spedali Civili 1, I-25123 Brescia, Italy. EM alessandra.marengoni@ki.se FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111] FX The InChianti study baseline (1998-2000) was supported as a 'targeted project' (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD9164 and 263 MD 821336); the InChianti follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111). Researchers' work was independent from funders. NR 45 TC 14 Z9 15 U1 1 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 24 IS 3 BP 559 EP 568 DI 10.3233/JAD-2011-101863 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 789EN UT WOS:000292496900013 PM 21297261 ER PT J AU Manaye, KF Allard, JS Kalifa, S Drew, AC Xu, GA Ingram, DK de Cabo, R Mouton, PR AF Manaye, Kebreten F. Allard, Joanne S. Kalifa, Sara Drew, Amy C. Xu, Guang Ingram, Donald K. de Cabo, Rafael Mouton, Peter R. TI 17 alpha-Estradiol Attenuates Neuron Loss in Ovariectomized Dtg A beta PP/PS1 Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; stereology; transgenic mice ID RANDOMIZED CONTROLLED-TRIAL; MILD COGNITIVE IMPAIRMENT; AMYLOID PRECURSOR PROTEIN; HEALTH INITIATIVE MEMORY; TRANSGENIC MOUSE MODEL; CENTRAL NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; POSTMENOPAUSAL WOMEN; BRAIN-INJURY; MEDIATED NEUROPROTECTION AB Quantitative microanalysis of brains from patients with Alzheimer's disease (AD) find neuronal loss and neuroinflammation in structures that control cognitive function. Though historically difficult to recapitulate in experimental models, several groups have recently reported that by middle-age, transgenic mice that co-express high levels of two AD-associated mutations, amyloid-beta protein precursor (A beta PPswe) and presenilin 1 (PS1(Delta E9)), undergo significant AD-type neuron loss in subcortical nuclei with heavy catecholaminergic projections to the hippocampal formation. Here we report that by 13 months of age these dtg A beta PPswe/PS1(Delta E9) mice also show significant loss of pyramidal neuron in a critical region for learning and memory, the CA1 subregion of hippocampus, as a direct function of amyloid-beta (A beta) aggregation. We used these mice to test whether 17 alpha-estradiol (17 alpha E2), a less feminizing and non-carcinogenic enantiomer of 17 beta-estradiol, protects against this CA1 neuron loss. Female dtg A beta PPswe/PS1(Delta E9) mice were ovariectomized at 8-9 months of age and treated for 60 days with either 17 alpha E2 or placebo via subcutaneous pellets. Computerized stereology revealed that 17 alpha E2 ameliorated the loss of neurons in CA1 and reduced microglial activation in the hippocampus. These findings support the view that 17 alpha E2, which may act through non-genomic mechanisms independent of traditional estrogen receptors, could prevent or delay the progression of AD in older men and women. C1 [Manaye, Kebreten F.; Allard, Joanne S.; Kalifa, Sara; Drew, Amy C.; Xu, Guang] Howard Univ, Coll Med, Dept Physiol & Biophys, Washington, DC 20059 USA. [Ingram, Donald K.] Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. [Allard, Joanne S.; de Cabo, Rafael; Mouton, Peter R.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Mouton, Peter R.] Univ S Florida, Sch Med, Dept Pathol & Cell Biol, Byrd Alzheimers Ctr, Tampa, FL 33620 USA. [Mouton, Peter R.] Univ S Florida, Sch Med, Res Inst, Tampa, FL 33620 USA. RP Manaye, KF (reprint author), Howard Univ, Coll Med, Dept Physiol & Biophys, Suite 2305,Adams Bldg,520 W St NW, Washington, DC 20059 USA. EM kmanaye@howard.edu RI de Cabo, Rafael/J-5230-2016 OI de Cabo, Rafael/0000-0002-3354-2442 FU NIH/NINDS [U54 NS42867, R01 AG026478]; Public Health Service (NIH) [MH076541-02A1, NS039407-06A1] FX The authors wish to acknowledge support from NIH/NINDS; Grant number: U54 NS42867, R01 AG026478 (RST), the Public Health Service (NIH extramural grants MH076541-02A1, NS039407-06A1), Drs. David R. Borchelt and Michael K. Lee for donation of founders for this study, and the NIA Intramural Program in Baltimore, Maryland. We would also like to acknowledge Dr. John Kwagyan for his assistance with the statistical analysis. NR 80 TC 4 Z9 4 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2011 VL 23 IS 4 BP 629 EP 639 DI 10.3233/JAD-2010-100993 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 743BE UT WOS:000288989600005 PM 21157032 ER PT J AU Hingson, R Heeren, T Winter, M Wechsler, H AF Hingson, Ralph Heeren, Tim Winter, Michael Wechsler, Henry TI "Alcohol-Related Vehicular Death Rates for College Students in the Commonwealth of Virginia" SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Letter C1 [Hingson, Ralph] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA. [Heeren, Tim] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Winter, Michael] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Wechsler, Henry] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Hingson, R (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane,Rm 2074, Bethesda, MD 20892 USA. EM rhingson@mail.nih.gov OI Heeren, Timothy/0000-0001-5643-3559 NR 3 TC 1 Z9 1 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PY 2011 VL 59 IS 7 BP 678 EP 679 DI 10.1080/07448481.2011.576294 PG 2 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 881IY UT WOS:000299478100016 PM 21823966 ER PT J AU Napora, JK Short, RG Muller, DC Carlson, OD Odetunde, JO Xu, XQ Carducci, M Travison, TG Maggio, M Egan, JM Basaria, S AF Napora, Joshua K. Short, Ryan G. Muller, Denis C. Carlson, Olga D. Odetunde, Juliana O. Xu, Xiaoqiang Carducci, Michael Travison, Thomas G. Maggio, Marcello Egan, Josephine M. Basaria, Shehzad TI High-Dose Isoflavones Do Not Improve Metabolic and Inflammatory Parameters in Androgen-Deprived Men With Prostate Cancer SO JOURNAL OF ANDROLOGY LA English DT Article DE Androgen deprivation; inflammation; metabolic syndrome ID HYPERCHOLESTEROLEMIC POSTMENOPAUSAL WOMEN; NECROSIS-FACTOR-ALPHA; DEPRIVATION THERAPY; SOY PROTEIN; INSULIN-RESISTANCE; PHYTOESTROGEN GENISTEIN; CHINESE WOMEN; PLASMA-LIPIDS; SERUM-LIPIDS; ESTROGEN AB The profound hypogonadism that occurs with androgen deprivation therapy (ADT) for prostate cancer (PCa) results in complications such as diabetes and metabolic syndrome that predispose to cardiovascular disease. Because phytoestrogens have been associated with an improvement in metabolic parameters, we evaluated their role in men undergoing ADT. Our objective was to evaluate the effects of high-dose isoflavones on metabolic and inflammatory parameters in men undergoing ADT. This was a randomized, double-blind, placebo-controlled, 12-week pilot study. Participants were randomly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo (20 g whole milk protein). The study was conducted at a tertiary care center in the United States. Thirty-three men (isoflavones = 17, placebo = 16) undergoing ADT for PCa completed this pilot study. Mean age in the 2 groups was 69 years and the majority of men were Caucasians. Mean duration of ADT in both groups was approximately 2 years (P = .70). The 2 groups were well matched at baseline. After 12 weeks of intervention, there was no significant difference in either metabolic or inflammatory parameters between the 2 groups. We found that high-dose isoflavones over a course of 12 weeks do not improve metabolic or inflammatory parameters in androgen-deprived men. C1 [Basaria, Shehzad] Boston Univ, Sch Med, Boston Med Ctr, Sect Endocrinol Diabet & Nutr,Div Endocrinol & Me, Boston, MA 02118 USA. [Napora, Joshua K.; Short, Ryan G.; Muller, Denis C.; Carlson, Olga D.; Odetunde, Juliana O.; Egan, Josephine M.] NIA, NIH, Clin Invest Lab, Diabet Sect, Baltimore, MD 21224 USA. [Xu, Xiaoqiang] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Carducci, Michael] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Maggio, Marcello] Univ Parma, Div Endocrinol & Metab, I-43100 Parma, Italy. RP Basaria, S (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Sect Endocrinol Diabet & Nutr,Div Endocrinol & Me, 670 Albany St,2nd Floor, Boston, MA 02118 USA. EM shehzad.basaria@bmc.org FU Intramural NIH HHS [Z01 AG000906-12] NR 47 TC 8 Z9 8 U1 1 U2 3 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2011 VL 32 IS 1 BP 40 EP 48 DI 10.2164/jandrol.110.010983 PG 9 WC Andrology SC Endocrinology & Metabolism GA 707LA UT WOS:000286286700007 PM 20798386 ER PT J AU Halberg, F Cornelissen, G Grambsch, P McCraty, R Beaty, L Siegelova, J Homolka, P Hillman, DC Finley, J Thomas, F Kino, T Revilla, M Schwartzkopff, O AF Halberg, Franz Cornelissen, Germaine Grambsch, Patricia McCraty, Rollin Beaty, Larry Siegelova, Jarmila Homolka, Pavel Hillman, Dewayne Carol Finley, Judy Thomas, Faithe Kino, Tomoshige Revilla, Miguel Schwartzkopff, Othild TI Personalized chronobiologic cybercare; other chronomics' progress by transdisciplinary cycles' congruences: season's appreciations 2009 SO JOURNAL OF APPLIED BIOMEDICINE LA English DT Review DE blood pressure; cancer; death; heart rate; time; nonphotic cycles; suicide; terrorism; vascular variability disorders (VVDs) ID SOLAR-ACTIVITY; TIME; PRESSURE; RHYTHMS; LIFE; BAKKEN,EARL,ELMER; FEEDSIDEWARDS; HYPERTENSION; PERIODICITY; WIND AB Originally a remembrance of an elderly physiologist, this paper illustrates the need for a standardized specification of certain experimental or survey conditions beyond those usually necessarily disclosed in conventional publications, namely calendar-dates, clock-times and geographic locations, to allow reference to helio-ionosphero-geomagnetics along with natural and artificial lighting and temperature. When possible, body times given by a marker rhythm also should be specified. A personalized chronobiologic cybercare can eventually include focus on infradians, beyond circadians. Benefits from longitudinal monitoring are: 1. Chronobiologically-interpreted blood pressure (BP) and heart rate (HR) monitoring enables the diagnosis and treatment of vascular variability anomalies (VVAs) or, if lasting in several 7-day records, disorders (VVDs), not yet screened for in practice, that increase cardiovascular disease risk independently of an elevated BP. 2. The optimal treatment time for the individual patient can be determined and potential harm avoided, since the same dose of the same medication for the same patient can help or harm depending only on when it is administered. 3. Benefit may be derived in cancer treatment timed according to marker rhythmometry. 4. The change from a spotcheck-based health care to one of internet-aided systematic self-surveillance by the automatic collection and analysis of time series stems from evidence that nonphotic and photic environmental influences affect biota, associations that may depend on geographic and temporal location. 5. Imaging in time includes formatting for time, globally and locally, for the mapping of a transdisciplinary spectrum of cycles involving "good" and "bad" strain in human physiology, versus sudden cardiac death, suicide and terrorism, all latter requiring rational countermeasures. C1 [Halberg, Franz; Cornelissen, Germaine; Beaty, Larry; Hillman, Dewayne Carol; Finley, Judy; Thomas, Faithe; Schwartzkopff, Othild] Univ Minnesota, Halberg Chronobiol Ctr, Minneapolis, MN 55455 USA. [Grambsch, Patricia] Univ Minnesota, Dept Biostat, Minneapolis, MN 55455 USA. [McCraty, Rollin] Inst HeartMath, Boulder Creek, CA USA. [Siegelova, Jarmila; Homolka, Pavel] Masaryk Univ, St Anna Teaching Hosp, Dept Funct Diagnost & Rehabil, Brno, Czech Republic. [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Revilla, Miguel] Univ Valladolid, Dept Appl Math, E-47002 Valladolid, Spain. RP Halberg, F (reprint author), Univ Minnesota, Halberg Chronobiol Ctr, MMC 8609,420 Delaware St SE, Minneapolis, MN 55455 USA. EM halbe001@umn.edu FU University of Minnesota Supercomputing Institute; [GM-13981] FX GM-13981 (FH) and University of Minnesota Supercomputing Institute (GC, FH). NR 105 TC 2 Z9 2 U1 1 U2 6 PU UNIV SOUTH BOHEMIA PI CESKA BUDEJOVICE PA FAC HEALTH & SOCIAL STUD, JIROVCOVA, CESKA BUDEJOVICE, 370 04, CZECH REPUBLIC SN 1214-021X J9 J APPL BIOMED JI J. Appl. Biomed. PY 2011 VL 9 IS 1 BP 1 EP 34 DI 10.2478/v10136-009-0022-8 PG 34 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 687LU UT WOS:000284780800001 ER PT J AU Li, Q Zheng, G Tiwari, R AF Li, Q. Zheng, G. Tiwari, R. TI Analysis of ordered categorical data with score averaging: with applications to case-control genetic associations SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE case-control genetic associations; MAX; ordered categorical data; robustness; score averaging tests; trend tests ID GENOME-WIDE ASSOCIATION; NUISANCE PARAMETER; STATISTICAL-METHODS; CONTINGENCY-TABLES; TREND TESTS; RISK; DRAWBACKS; MAXIMUM; CANCER; CHOICE AB The trend test is often used for the analysis of 2 x K ordered categorical data, in which K pre-specified increasing scores are used. There have been discussions on how to assign these scores and the impact of the outcomes on different scores. The scores are often assigned based on the data-generating model. When this model is unknown, using the trend test is not robust. We discuss the weighted average of a trend test over all scientifically plausible choices of scores or models. This approach is more computationally efficient than a commonly used robust test MAX when K is large. Our discussion is for any ordered 2 x K table, but simulation and applications to real data are focused on case-control genetic association studies. Although there is no single test optimal for all choices of scores, our numerical results show that some score averaging tests can achieve the performance of MAX. C1 [Li, Q.] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. [Zheng, G.] US Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA. [Tiwari, R.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. RP Li, Q (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. EM liqz@amss.ac.cn FU National Young Science Foundation of China [10901155] FX The work of Q. Li was supported in part by the National Young Science Foundation of China (grant 10901155). NR 24 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2011 VL 38 IS 9 BP 1833 EP 1843 DI 10.1080/02664763.2010.529881 PG 11 WC Statistics & Probability SC Mathematics GA 873YF UT WOS:000298921300006 ER PT J AU Ma, CX Vexler, A Schisterman, EF Tian, LL AF Ma, Chang-Xing Vexler, Albert Schisterman, Enrique F. Tian, Lili TI Cost-efficient designs based on linearly associated biomarkers SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE biological samples; cost-efficient sampling; D-optimality; grouping; linear regression; pooling design; random sampling; sampling designs ID ROC CURVE ANALYSIS; POOLED ASSESSMENTS; DEFECTIVE MEMBERS; LARGE POPULATIONS; BREAST-CANCER; BIOSPECIMENS; SUBJECT; RISK; LIMIT AB A major limiting factor in much of the epidemiological and environmental researches is the cost of measuring the biomarkers or analytes of interest. Often, the number of specimens available for analysis is greater than the number of assays that is budgeted for. These assays are then performed on a random sample of specimens. Regression calibration is then utilized to infer biomarker levels of expensive assays from other correlated biomarkers that are relatively inexpensive to obtain and analyze. In other contexts, use of pooled specimens has been shown to increase efficiency in estimation. In this article, we examine two types of pooling in lieu of a random sample. The first is random (or traditional) pooling, and we characterize the second as "optimal" pooling. The second, which we propose for regression analysis, is pooling based on specimens ranked on the less expensive biomarker. The more expensive assay is then performed on the pool of relatively similar measurements. The optimal nature of this technique is also exemplified via Monte Carlo evaluations and real biomarker data. By displaying the considerable robustness of our method via a Monte Carlo study, it is shown that the proposed pooling design is a viable option whenever expensive assays are considered. C1 [Ma, Chang-Xing; Vexler, Albert; Tian, Lili] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. [Schisterman, Enrique F.] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA. RP Ma, CX (reprint author), SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. EM cxma@buffalo.edu OI Schisterman, Enrique/0000-0003-3757-641X NR 18 TC 8 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2011 VL 38 IS 12 BP 2739 EP 2750 DI 10.1080/02664763.2011.567254 PG 12 WC Statistics & Probability SC Mathematics GA 873ZJ UT WOS:000298924500005 ER PT J AU Patlolla, A McGinnis, B Tchounwou, P AF Patlolla, Anita McGinnis, Brittney Tchounwou, Paul TI Biochemical and histopathological evaluation of functionalized single-walled carbon nanotubes in Swiss-Webster mice SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE single-walled carbon nanotube; reactive oxygen species; lipid hydroperoxide; serum aminotransferases; alkaline phosphatases; Swiss-Webster mice; histopathology; hepatotoxicity ID NEAR-INFRARED FLUORESCENCE; OXIDATIVE STRESS; IN-VITRO; CYTOTOXICITY; TOXICITY; CELLS; BIOAVAILABILITY; NANOPARTICLES; DEPENDENCE; FULLERENE AB With their unique physicochemical properties, single-walled carbon nanotubes (SWCNTs) have many potential new applications in medicine and industry. A biomedical application of single-wall carbon nanotubes such as drug delivery requires a fundamental understanding of their fate and toxicological profile after administration. However, the toxicity of SWCNT is barely known when they are introduced into the blood circulation, which is especially vital for their biomedical applications. The aim of this study was to assess the effects, after intraperitoneal injection, of functionalized SWCNTs (carboxyl groups) on reactive oxygen species (ROS) induction and various hepatotoxicity markers (ALT, AST, ALP, LPO and morphology of liver) in the mouse model. We exposed mice to three different concentrations of functionalized SWCNTs (0.25, 0.5 and 0.75 mg kg(-1) b.w.) and two controls (negative and positive). Samples were collected 24 h after the last treatment following standard protocols. Exposure to carboxylated functionalized SWCNT induced ROS and enhanced the activities of serum amino-transferases (ALT/AST) and alkaline phosphatases (ALP) and the concentration of lipid hydroperoxide compared with control. Histopathology of the exposed liver showed a statistically significant effect in the morphological alterations of the tissue compared with controls. The cellular findings reported here do suggest that purified carboxylated functionalized SWCNT has the potential to induce hepatotoxicity in Swiss-Webster mice through activation of the mechanisms of oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies. However, more studies to clarify the role of functionalization in the in vivo toxicity of SWCNTs are required and parallel comparison is preferred. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Patlolla, Anita; Tchounwou, Paul] Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS USA. [McGinnis, Brittney] Dillard Univ, New Orleans, LA USA. RP Patlolla, A (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH RCMI Ctr Environm Hlth, Mol Toxicol Res Lab, Jackson, MS USA. EM anita.k.patlolla@jsums.edu FU NSF-REU [DMR-0755433]; RCMI-NCRR at Jackson State University [2G12RR01349-12] FX This research was financially support by Title III, Strengthening HBCUs, Center for University Scholar Program, NSF-REU grant no. DMR-0755433 and RCMI-NCRR grant no. 2G12RR01349-12 at Jackson State University. NR 45 TC 24 Z9 24 U1 0 U2 12 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD JAN PY 2011 VL 31 IS 1 BP 75 EP 83 DI 10.1002/jat.1579 PG 9 WC Toxicology SC Toxicology GA 708FF UT WOS:000286347000009 PM 20737426 ER PT J AU Mason, RP Jacob, RF Kubant, R Walter, MF Bellamine, A Jacoby, A Mizuno, Y Malinski, T AF Mason, R. Preston Jacob, Robert F. Kubant, Ruslan Walter, Mary F. Bellamine, Aouatef Jacoby, Adam Mizuno, Yoshiko Malinski, Tadeusz TI Effect of Enhanced Glycemic Control with Saxagliptin on Endothelial Nitric Oxide Release and CD40 Levels in Obese Rats SO JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS LA English DT Article DE Saxagliptin; Endothelium; Nitric oxide synthase; Diabetes; CD40 ID DIPEPTIDYL-PEPTIDASE-IV; INSULIN-RESISTANCE; MICE; INHIBITORS; DISEASE; DIMETHYLARGININE; ATHEROSCLEROSIS; BIOAVAILABILITY; MECHANISMS; SYNTHASE AB Aim: Endothelial cell (EC) dysfunction contributes to insulin resistance in diabetes and is characterized by reduced nitric oxide (NO) release, increased nitroxidative stress and enhanced inflammation. The purpose of this study was to test the effect of improved postprandial glucose control on EC function in insulin-resistant rats as compared to fasting glucose (FG) changes. Methods: Obese Zucker rats were treated with 10 mg/kg/day saxagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, for 4 or 8 weeks and compared to lean rats. NO and peroxynitrite (ONOO-) release from aortic and glomerular ECs was measured ex vivo using amperometric approaches and correlated with FG, postprandial glucose, insulin, soluble CD40 (sCD40) and L-citrulline levels. Results: Saxagliptin treatment improved NO production and reduced ONOO- release prior to any observed changes in FG levels. In untreated obese animals, NO release from aortic and glomerular ECs decreased by 22% and 31%, respectively, while ONOO- release increased by 26% and 40%. Saxagliptin increased aortic and glomerular NO release by 18% and 31%, respectively, with comparable reductions in ONOO- levels; the NO/ONOO- ratio, an indicator of NO synthase coupling, increased by >40%. Improved glycemic control was further associated with a reduction in sCD40 levels by more than ten-fold (from 300 +/- 206 to 22 +/- 22 pg/mL, p<0.001). Conclusion: These findings indicate that enhanced glycemic control with DPP4 inhibition improved NO release and reduced inflammation in a manner not predicted by FG changes alone. C1 [Mason, R. Preston; Mizuno, Yoshiko] Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Mason, R. Preston; Jacob, Robert F.; Mizuno, Yoshiko] Elucida Res LLC, Beverly, MA USA. [Kubant, Ruslan; Jacoby, Adam; Malinski, Tadeusz] Ohio Univ, Dept Biochem, Athens, OH 45701 USA. [Walter, Mary F.] NIH, Bethesda, MD 20892 USA. [Bellamine, Aouatef] Bristol Myers Squibb Co, Princeton, NJ USA. RP Mason, RP (reprint author), 100 Cummings Ctr, Suite 135L, Beverly, MA 01915 USA. EM rpmason@elucidaresearch.com FU Bristol-Myers Squibb; Astra Zeneca FX This study was supported, in part, by a basic research grant from Bristol-Myers Squibb and Astra Zeneca, who also provided the drug used in this study. NR 32 TC 27 Z9 33 U1 2 U2 9 PU JAPAN ATHEROSCLEROSIS SOC PI TOKYO PA NICHINAI-KAIKAN B1, 3-28-8 HONGO BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1340-3478 EI 1880-3873 J9 J ATHEROSCLER THROMB JI J. Atheroscler. Thromb. PY 2011 VL 18 IS 9 BP 774 EP 783 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 856VR UT WOS:000297672900006 PM 21670556 ER PT J AU Gawel, D Jonczyk, P Fijalkowska, IJ Schaaper, RM AF Gawel, Damian Jonczyk, Piotr Fijalkowska, Iwona J. Schaaper, Roel M. TI dnaX36 Mutator of Escherichia coli: Effects of the tau Subunit of the DNA Polymerase III Holoenzyme on Chromosomal DNA Replication Fidelity SO JOURNAL OF BACTERIOLOGY LA English DT Article ID UNIQUE C-TERMINUS; LAGGING-STRAND; DISTINCT DOMAINS; SLIDING CLAMP; THETA-SUBUNIT; ALPHA-SUBUNIT; IN-VIVO; POL-IV; MUTAGENESIS; REPLISOME AB The Escherichia coli dnaX36 mutant displays a mutator effect, reflecting a fidelity function of the dnaX-encoded tau subunit of the DNA polymerase III (Pol III) holoenzyme. We have shown that this fidelity function (i) applies to both leading- and lagging-strand synthesis, (ii) is independent of Pol IV, and (iii) is limited by Pol II. C1 [Gawel, Damian; Schaaper, Roel M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Gawel, Damian; Jonczyk, Piotr; Fijalkowska, Iwona J.] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov RI Fijalkowska, Iwona/I-7796-2016 FU NIH [Z01 ES065086]; National Institute of Environmental Health Sciences; Polish Ministry of Science and Higher Education [2 PO4A 061 30] FX This research was supported by project no. Z01 ES065086 of the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and by grant 2 PO4A 061 30 (to I.J.F. and P.J.) from the Polish Ministry of Science and Higher Education. NR 36 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2011 VL 193 IS 1 BP 296 EP 300 DI 10.1128/JB.01191-10 PG 5 WC Microbiology SC Microbiology GA 692GY UT WOS:000285142500030 PM 21036999 ER PT J AU Martin, RG Rosner, JL AF Martin, Robert G. Rosner, Judah L. TI Promoter Discrimination at Class I MarA Regulon Promoters Mediated by Glutamic Acid 89 of the MarA Transcriptional Activator of Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIPLE-ANTIBIOTIC-RESISTANCE; ALANINE-SCANNING MUTAGENESIS; OXIDATIVE STRESS REGULON; RNA-POLYMERASE; DNA-BINDING; MARA/SOXS/ROB REGULON; INDUCIBLE PROMOTERS; TERMINAL DOMAIN; ALPHA-SUBUNIT; BASE-STACKING AB Three paralogous transcriptional activators MarA, SoxS, and Rob, activate > 40 Escherichia coli promoters. To understand why MarA does not activate certain promoters as strongly as SoxS, we compared MarA, MarA mutants, and SoxS for their abilities to activate 16 promoters and to bind their cognate marbox binding sites. Replacement of the MarA glutamic acid residue 89 with alanine greatly increased the marbox binding and activation of many class I promoters. Like cells constitutive for SoxS, cells expressing the MarA with the E89A mutation were more resistant to superoxides than those harboring WT MarA. The activities of several other E89 substitutions ranked as follows: E89A > E89G > E89V > WT > E89D. Increased binding and activation occurred only at class I promoters when the 12th base of the promoter's marbox (a position at which there is no known interaction between the marbox and MarA) was not a T residue. Furthermore, WT MarA binding to a synthetic marbox in vitro was enhanced when the phosphate group between positions 12 and 13 was eliminated on one strand. The results demonstrate that relatively minor changes in a single amino acid side chain (e.g., alanine to valine or glutamic acid to aspartic acid) can strongly influence activity despite any evidence that the side chain is involved in positive interactions with either DNA or RNA polymerase. We present a model which attributes the differences in binding and activation to the interference between the beta- and gamma-carbons of the amino acid at position 89 and the phosphate group between positions 12 and 13. C1 [Martin, Robert G.; Rosner, Judah L.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, RG (reprint author), NIDDK, Mol Biol Lab, NIH, Bldg 5,Rm 333,9000 Rockville Pike, Bethesda, MD 20892 USA. EM rgmartin@helix.nih.gov FU NIH, NIDDK FX This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 47 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2011 VL 193 IS 2 BP 506 EP 515 DI 10.1128/JB.00360-10 PG 10 WC Microbiology SC Microbiology GA 699TM UT WOS:000285685700019 PM 21097628 ER PT J AU Foskett, A Alnaeeli, M Wang, L Teng, RF Noguchi, CT AF Foskett, Amanda Alnaeeli, Mawadda Wang, Li Teng, Ruifeng Noguchi, Constance T. TI The Effects of Erythropoietin Dose Titration during High-Fat Diet-Induced Obesity SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID INSULIN-RESISTANCE; IN-VIVO; INFLAMMATION; RECEPTOR; ANEMIA; LEADS; MICE; DIFFERENTIATION; INTERLEUKIN-18; DOMAINS AB Erythropoietin (Epo) is a pleotropic cytokine with several nonhematopoietic tissue effects. High-dose Epo treatment-mediated effects on body weight, fat mass and glucose tolerance have recently been reported, thus extending its pleotropic effects to fat and glucose metabolism. However, the exact dose range of Epo treatment required for such effects remains unidentified to date. We investigated Epo dosage effect (up to 1000 U/kg) on hematocrit, body weight, body composition, glucose metabolism, food intake, and physical activity, during high-fat diet-induced obesity. We report that Epo doses (1000, 600, 300, and 150 U/kg) significantly reduced body weight gain and fat mass, while, only Epo doses of 300 U/kg and higher significantly affected glucose tolerance. None of the tested Epo doses showed any detectable effects on food intake, and only 1000 U/kg dose significantly increased physical activity, suggesting that these parameters may only be partially responsible for the metabolic effects of Epo treatment. C1 [Foskett, Amanda; Alnaeeli, Mawadda; Wang, Li; Teng, Ruifeng; Noguchi, Constance T.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Noguchi, CT (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health FX The authors thank Oksana Gavrilova and the NIDDK Intramural Program Mouse Metabolism Core Facility for their excellent technical assistance in performing body composition analysis, serum insulin ELISA, and physical activity measurements. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health. Amanda Foskett and Mawadda Alnaeeli contributed equally to this work. NR 27 TC 12 Z9 12 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 373781 DI 10.1155/2011/373781 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 867FA UT WOS:000298439100001 ER PT J AU Joyce, MG Sun, PD AF Joyce, M. Gordon Sun, Peter D. TI The Structural Basis of Ligand Recognition by Natural Killer Cell Receptors SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID VIRUS-INFECTED CELLS; MHC CLASS-I; ACTIVATING IMMUNORECEPTOR NKG2D; HUMAN DENDRITIC CELLS; C-TYPE LECTIN; CRYSTAL-STRUCTURE; INHIBITORY RECEPTOR; CYTOTOXICITY RECEPTORS; HLA-E; EXTRACELLULAR DOMAIN AB Natural killer cells are a group of lymphocytes which function as tightly controlled surveillance operatives which identify transformed cells through a discrete balance of activating and inhibitory receptors ultimately leading to the destruction of incongruent cells. The understanding of this finely tuned balancing act has been aided by the high-resolution structure determination of activating and inhibitory receptors both alone and in complex with their ligands. This paper collates these structural studies detailing the aspects which directly relate to the natural killer cell function and serves to inform both the specialized structural biologist reader and a more general immunology audience. C1 [Joyce, M. Gordon; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This paper is funded by the intramural research funding of National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 76 TC 14 Z9 14 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 203628 DI 10.1155/2011/203628 PG 15 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 787VL UT WOS:000292404700001 ER PT J AU Kim, YS Milner, JA AF Kim, Young S. Milner, John A. TI Bioactive Food Components and Cancer-Specific Metabonomic Profiles SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; INHIBITS FATTY-ACID; MASS-SPECTROMETRY; HUMAN PLASMA; TRANS-RESVERATROL; METABOLIC PROFILE; PROSTATE-CANCER; RAT HEPATOCYTES; GLUCOSE-UPTAKE; TUMOR-CELLS AB Cancer cells possess unique metabolic signatures compared to normal cells, including shifts in aerobic glycolysis, glutaminolysis, and de novo biosynthesis of macromolecules. Targeting these changes with agents (drugs and dietary components) has been employed as strategies to reduce the complications associated with tumorigenesis. This paper highlights the ability of several food components to suppress tumor-specific metabolic pathways, including increased expression of glucose transporters, oncogenic tyrosine kinase, tumor-specific M2-type pyruvate kinase, and fatty acid synthase, and the detection of such effects using various metabonomic technologies, including liquid chromatography/mass spectrometry (LC/MS) and stable isotope-labeled MS. Stable isotope-mediated tracing technologies offer exciting opportunities for defining specific target(s) for food components. Exposures, especially during the early transition phase from normal to cancer, are critical for the translation of knowledge about food components into effective prevention strategies. Although appropriate dietary exposures needed to alter cellular metabolism remain inconsistent and/or ill-defined, validated metabonomic biomarkers for dietary components hold promise for establishing effective strategies for cancer prevention. C1 [Kim, Young S.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Kim, YS (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. EM yk47s@nih.gov NR 69 TC 10 Z9 10 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 721213 DI 10.1155/2011/721213 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 698RD UT WOS:000285610000001 ER PT J AU Soldin, OP Chung, SH Mattison, DR AF Soldin, Offie P. Chung, Sarah H. Mattison, Donald R. TI Sex Differences in Drug Disposition SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID MENSTRUAL-CYCLE; HEALTHY-VOLUNTEERS; BODY-WEIGHT; CLINICAL-PHARMACOLOGY; PERSONALIZED MEDICINE; OCCUPATIONAL-HEALTH; CYTOCHROME-P450 3A4; ANTIDIABETIC DRUGS; ESTROGEN-RECEPTOR; IN-VITRO AB Physiological, hormonal, and genetic differences between males and females affect the prevalence, incidence, and severity of diseases and responses to therapy. Understanding these differences is important for designing safe and effective treatments. This paper summarizes sex differences that impact drug disposition and includes a general comparison of clinical pharmacology as it applies to men and women. C1 [Soldin, Offie P.; Chung, Sarah H.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20057 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Physiol, Washington, DC 20057 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20057 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, LL, Washington, DC 20057 USA. [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD 20852 USA. RP Soldin, OP (reprint author), Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA. EM os35@georgetown.edu RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU NIH/NICHD [5U10HD0478925]; Office of Research on Women's Health; FAMRI FX Dr. Soldin is partially supported by NIH/NICHD-supplement to the Obstetric-Fetal Pharmacology Research Unit Network Grant 5U10HD0478925, funds from the Office of Research on Women's Health and FAMRI Clinical Innovator Award. NR 113 TC 38 Z9 39 U1 1 U2 8 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 EI 1110-7251 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 187103 DI 10.1155/2011/187103 PG 14 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 760SH UT WOS:000290343600001 ER PT J AU Vergati, M Schlom, J Tsang, KY AF Vergati, Matteo Schlom, Jeffrey Tsang, Kwong Y. TI The Consequence of Immune Suppressive Cells in the Use of Therapeutic Cancer Vaccines and Their Importance in Immune Monitoring SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID REGULATORY T-CELLS; TUMOR-ASSOCIATED MACROPHAGES; HEPATOCELLULAR-CARCINOMA PATIENTS; CHRONIC LYMPHOCYTIC-LEUKEMIA; RESISTANT PROSTATE-CANCER; PERIPHERAL-BLOOD; METASTATIC MELANOMA; ANTITUMOR-ACTIVITY; BREAST-CANCER; RESPONSES AB Evaluating the number, phenotypic characteristics, and function of immunosuppressive cells in the tumor microenvironment and peripheral blood could elucidate the antitumor immune response and provide information to evaluate the efficacy of cancer vaccines. Further studies are needed to evaluate the correlation between changes in immunosuppressive cells and clinical outcomes of patients in cancer vaccine clinical trials. This paper focuses on the role of T-regulatory cells, myeloid-derived suppressor cells, and tumor-associated macrophages in cancer and cancer immunotherapy and their role in immune monitoring. C1 [Vergati, Matteo; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 80 TC 5 Z9 8 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 182413 DI 10.1155/2011/182413 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 728OA UT WOS:000287882200001 ER PT J AU Whiteside, TL Gulley, JL Clay, TM Tsang, KY AF Whiteside, Theresa L. Gulley, James L. Clay, Timothy M. Tsang, Kwong Yok TI Immunologic Monitoring of Cellular Immune Responses in Cancer Vaccine Therapy SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Editorial Material ID PROSTATE-CANCER C1 [Clay, Timothy M.; Tsang, Kwong Yok] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Whiteside, Theresa L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA. [Whiteside, Theresa L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tsang, KY (reprint author), Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. EM tsangkwo@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 9 TC 4 Z9 4 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 370374 DI 10.1155/2011/370374 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 802XM UT WOS:000293544300001 ER PT J AU Berger, VW Vali, B AF Berger, Vance W. Vali, Behrang TI Intent-to-Randomize Corrections for Missing Data Resulting from Run-In Selection Bias in Clinical Trials for Chronic Conditions SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Enrichment; Intent-to-Randomize; Missing Completely at Random; Run-in ID PHYSICIANS-HEALTH; ENRICHMENT; PERIOD; EFFICIENCY; VALIDITY; DESIGNS AB In many clinical trials for chronic conditions a run-in period is used prior to randomization. Often, only those participants who meet certain criteria during the run-in phase go on to get randomized. The others, along with the information that they might have provided, are excluded from the study. This exclusion of the relevant response data from any subsequent study analysis can be considered as resulting in missing data; although quite common in practice, this approach has expectedly been shown to create a bias in favor of the active treatment when this active treatment is used during the run-in. Hence, many randomized clinical trials report overly optimistic results, with the extent of the bias depending in large part on how many otherwise eligible subjects were excluded due to the use of the run-in. If these biased trials are to contribute valid information to medical decision making, then the biases need to be corrected, and this involves accounting for all participants who were intended to be randomized. We propose specific imputation methods for doing so. C1 [Berger, Vance W.] NCI, EPN, Bethesda, MD 20892 USA. [Vali, Behrang] US FDA, Div Biometr 3, OB OTS CDER, Silver Spring, MD USA. RP Berger, VW (reprint author), NCI, EPN, Suite 3131,6130 Execut Blvd, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 25 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 263 EP 270 AR PII 934436828 DI 10.1080/10543406.2011.550107 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800007 PM 21391000 ER PT J AU Ishizuka, H Garcia-Palacios, V Lu, GW Subler, MA Zhang, HJ Boykin, CS Choi, SJ Zhao, LE Patrene, K Galson, DL Blair, HC Hadi, TM Windle, JJ Kurihara, N Roodman, GD AF Ishizuka, Hisako Garcia-Palacios, Veronica Lu, Ganwei Subler, Mark A. Zhang, Heju Boykin, Christina S. Choi, Sun Jin Zhao, Liena Patrene, Kenneth Galson, Deborah L. Blair, Harry C. Hadi, Tamer M. Windle, Jolene J. Kurihara, Noriyoshi Roodman, G. David TI ADAM8 Enhances Osteoclast Precursor Fusion and Osteoclast Formation In Vitro and In Vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ADAM8; TRANSGENIC/KNOCKOUT MICE; ADHESION MOLECULES; CELL DIFFERENTIATION; OSTEOCLAST ID STIMULATING FACTOR; DC-STAMP; BONE; CELL; MICE; DIFFERENTIATION; ALPHA(9)BETA(1); DISINTEGRIN; ACTIVATION; EXPRESSION AB ADAM8 expression is increased in the interface tissue around a loosened hip prosthesis and in the pannus and synovium of patients with rheumatoid arthritis, but its potential role in these processes is unclear. ADAM8 stimulates osteoclast (OCL) formation, but the effects of overexpression or loss of expression of ADAM8 in vivo and the mechanisms responsible for the effects of ADAM8 on osteoclastogenesis are unknown. Therefore, to determine the effects of modulating ADAM expression, we generated tartrate-resistant acid phosphatase (TRAP)-ADAM8 transgenic mice that overexpress ADAM8 in the OCL lineage and ADAM8 knockout (ADAM8 KO) mice. TRAP-ADAM8 mice developed osteopenia and had increased numbers of OCL precursors that formed hypermultinucleated OCLs with an increased bone-resorbing capacity per OCL. They also had an enhanced differentiation capacity, increased TRAF6 expression, and increased NF-kappa B, Erk, and Akt signaling compared with wild-type (WT) littermates. This increased bone-resorbing capacity per OCL was associated with increased levels of p-Pyk2 and p-Src activation. In contrast, ADAMS KO mice did not display a bone phenotype in vivo, but unlike WT littermates, they did not increase RANKL production, OCL formation, or calvarial fibrosis in response to tumor necrosis factor alpha (TNF-alpha) in vivo. Since loss of ADAM8 does not inhibit basal bone remodeling but only blocks the enhanced OCL formation in response to TNF-TNF-alpha, these results suggest that ADAM8 may be an attractive therapeutic target for preventing bone destruction associated with inflammatory disease. (C) 2011 American Society for Bone and Mineral Research. C1 [Roodman, G. David] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. [Ishizuka, Hisako; Garcia-Palacios, Veronica; Lu, Ganwei; Zhao, Liena; Patrene, Kenneth; Galson, Deborah L.; Kurihara, Noriyoshi; Roodman, G. David] Univ Pittsburgh, Med Ctr, Dept Med Hematol Oncol, Pittsburgh, PA USA. [Ishizuka, Hisako; Garcia-Palacios, Veronica; Lu, Ganwei; Zhao, Liena; Patrene, Kenneth; Galson, Deborah L.; Kurihara, Noriyoshi; Roodman, G. David] Univ Pittsburgh, Med Ctr, Ctr Bone Biol, Pittsburgh, PA USA. [Subler, Mark A.; Boykin, Christina S.; Hadi, Tamer M.; Windle, Jolene J.] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA. [Zhang, Heju; Windle, Jolene J.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Choi, Sun Jin] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Blair, Harry C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RP Roodman, GD (reprint author), VA Pittsburgh Healthcare Syst, R&D 151-U,Univ Dr C, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu RI Galson, Deborah/E-9370-2010; OI Galson, Deborah/0000-0002-2045-8807; Windle, Jolene/0000-0001-6690-385X FU Novartis Pharmaceuticals; NIH [RO1AR041336, P30 CA016059, R01 AR057310] FX GDR reports having served as a consultant to Amgen, Celgene, Acceleron, and Millenium and receives grant support from Novartis Pharmaceuticals. All the other authors state that they have no conflicts of interest.; This work was supported by a VA Merit Review Grant and by NIH Grants RO1AR041336 (to GDR), P30 CA016059 (to JJW), and R01 AR057310 (to DLG). The materials are the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Research and Development. NR 25 TC 17 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2011 VL 26 IS 1 BP 169 EP 181 DI 10.1002/jbmr.199 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704FD UT WOS:000286035600019 PM 20683884 ER PT J AU Ono, M Inkson, CA Kilts, TM Young, MF AF Ono, Mitsuaki Inkson, Colette A. Kilts, Tina M. Young, Marian F. TI WISP-1/CCN4 Regulates Osteogenesis by Enhancing BMP-2 Activity SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE WISP1; GROWTH FACTORS; BMP; CYTOKINES; OSTEOPROGENITORS; CCN ID TISSUE-GROWTH-FACTOR; BONE MORPHOGENETIC PROTEINS; COMBINATORIAL GENE-THERAPY; HUMAN CHONDROSARCOMA CELLS; FAMILY-MEMBER WISP3; CCN FAMILY; OSTEOBLAST DIFFERENTIATION; ALPHA-V-BETA-3 INTEGRIN; EXTRACELLULAR-MATRIX; SKELETAL DEVELOPMENT AB Wnt-induced secreted protein 1 (WISP-1/CCN4) is a member of the CCN family that is highly expressed in skeletal tissue and in osteoprogenitor cells induced to differentiate in vitro. To determine the function of WISP-1 during osteogeneis, osteogenic bone marrow stromal cells (BMSCs) were transduced with WISP-1 adenovirus (ad WISP-1) in the presence or absence of bone morphogenetic protein 2 (BMP-2) adenovirus (adBMP-2). WISP-1 overexpression enhanced the ability of BMP-2 to direct BMSCs toward osteogenic differentiation and appeared to work by stimulating Smad-1/5/8 phosphorylation and activation. The ability of WISP-1 to enhance BMP-2 activity also was shown in vivo using an ectopic osteogenesis assay with BMSCs transduced with WISP-1, BMP-2, or both. When BMSCs were infected with lentivirus containing human WISP1 shRNA, they formed less bone in vivo and were less responsive to BMP-2, confirming that WISP-1 and BMP-2 have a functional interaction. Immunoprecipitation (IP) and Western blot analysis showed that WISP-1 bound directly to BMP-2 and showed that WISP-1 increased BMP-2 binding to hBMSCs in a dose-dependent fashion. To understand how WISP-1 enhanced BMP-2 signaling, the influence of WISP-1 on integrin expression was analyzed. WISP-1 induced the mRNA and protein levels of alpha(5)-integrin and, further, was found to bind to it. Antibody-blocking experiments showed that the BMP-2 binding to BMSCs that was enhanced by WISP-1 was completely neutralized by treatment with anti-integrin alpha(5)beta(1) antibody. Pilot studies and the use of transgenic mice that overexpressed human WISP-1 in preosteoblasts had increased bone mineral density (BMD), trabecular thickness, and bone volume (BV/TV) over wild-type controls, supporting observations using human osteoprogenitors that WISP-1 has a positive influence on osteogenesis in vivo. In conclusion, these studies show, for the first time, that WISP-1 has a. positive influence on bone cell differentiation and function and may work by enhancing the effects of BMP-2 to increase osteogenesis through a mechanism potentially involving binding to integrin alpha(5)beta(1). (C) 2011 American Society for Bone and Mineral Research. C1 [Ono, Mitsuaki; Inkson, Colette A.; Kilts, Tina M.; Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Young, MF (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 225,9000 Rockville Pike, Bethesda, MD 20892 USA. EM myoung@dir.nidcr.nih.gov OI Inkson, Colette/0000-0003-1215-312X FU Division of Intramural Research of the NIDCR, NIH FX This work was supported by the Division of Intramural Research of the NIDCR of the Intramural Research Program, NIH. We are grateful to Dr S Kuznetsov (NIDCR) and Dr P Robey (NIDCR) for advice on the use and analysis of human bone marrow stromal cells, to Dr A Kulkarni (NIDCR) and Dr T Sreenath (NIDCR) for assistance in preparation of the WISP1-Tg line, and to Dr L Fisher (NIDCR) for advice on the preparation of anti-WISP1 antisera (LF-187). NR 79 TC 51 Z9 56 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2011 VL 26 IS 1 BP 193 EP 208 DI 10.1002/jbmr.205 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704FD UT WOS:000286035600021 PM 20684029 ER PT J AU Walter, BA Gomez-Macias, G Valera, VA Sobel, M Merino, MJ AF Walter, Beatriz A. Gomez-Macias, Gabriela Valera, Vladimir A. Sobel, Mark Merino, Maria J. TI miR-21 Expression in Pregnancy-Associated Breast Cancer: A Possible Marker of Poor Prognosis SO JOURNAL OF CANCER LA English DT Article DE Pregnancy-associated breast cancer; breast cancer; microRNA; miR-21; PTEN AB Aims: microRNAs (miRNAs) are a class of small noncoding RNAs that can act as key modulators in tumorigenesis-related genes. Specifically, it has been suggested that miR-21 overexpression plays a role in the development and progression of breast cancer. So far, the role of miRNAs in pregnancy-associated breast cancer (PABC) has not been investigated. Methods and Results: We evaluated miR-21 expression by quantitative RT-PCR in 35 patients, 25 with PABC and 10 control breast cancer cases not pregnancy-associated with similar clinicopathological features. We then analyzed protein expression for PTEN, BCL2 and PDCD4 as miR-21 target genes by IHC, and finally correlated the results with patients' clinicopathological features. Significant overexpression of miR-21 in PABC tumors compared to normal adjacent tissue was found. Overexpression of miR-21 was frequently found in high grade tumors with loss of hormone receptor expression and was significantly associated with positive lymph nodes (p=0.025). In PABC patients, PTEN, BCL2 and PDCD4 target protein expression was decreased in 80%, 76% and 40% respectively. Conclusion: Our study supports the involvement of miR-21 in breast cancer progression and metastasis formation in PABC implying a role of this miRNA as a marker for poor prognosis in PABC patients. C1 [Walter, Beatriz A.; Valera, Vladimir A.; Sobel, Mark; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Gomez-Macias, Gabriela] Univ Autonoma Nuevo Leon, Dept Pathol & Cytopathol, Monterrey, Mexico. RP Merino, MJ (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr Bldg 10 Room 5B53,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mjmerino@mail.nih.gov FU Intramural Research Program of the NIH, NCI FX This research was supported by the Intramural Research Program of the NIH, NCI. NR 32 TC 20 Z9 20 U1 1 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 67 EP 75 DI 10.7150/jca.2.67 PG 9 WC Oncology SC Oncology GA V28QM UT WOS:000208695300007 PM 21326627 ER PT J AU Feng, MQ Zhang, JL Anver, M Hassan, R Ho, M AF Feng, Mingqian Zhang, Jingli Anver, Miriam Hassan, Raffit Ho, Mitchell TI In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice SO JOURNAL OF CANCER LA English DT Article DE H226/NCI-H226; mouse xenograft model; in vivo bioluminescence imaging; malignant mesothelioma; mesothelin; monoclonal antibody; immunotoxin; preclinical model AB Malignant mesothelioma (MM) causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP) fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL) that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo. C1 [Feng, Mingqian; Zhang, Jingli; Hassan, Raffit; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Anver, Miriam] NCI, Pathol Histotechnol Lab, SAIC Frederick, Frederick, MD 21702 USA. RP Ho, M (reprint author), NCI, Antibody Therapy Unit, Mol Biol Lab, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA. EM homi@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Mesothelioma Applied Research Foundation; National Cancer Institute, NIH [HHSN261288800001E] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, in part by a Mesothelioma Applied Research Foundation Grant in Honor of Craig Kozicki to MH, and in part by the National Cancer Institute, NIH under contract No. HHSN261288800001E. NR 26 TC 10 Z9 11 U1 2 U2 3 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 123 EP 131 DI 10.7150/jca.2.123 PG 9 WC Oncology SC Oncology GA V28QM UT WOS:000208695300014 PM 21479131 ER PT J AU Guerrero, MA Lindsay, S Suh, I Vriens, MR Khanafshar, E Shen, WT Gosnell, J Kebebew, E Duh, QY Clark, OH AF Guerrero, Marlon A. Lindsay, Sheila Suh, Insoo Vriens, Menno R. Khanafshar, Elham Shen, Wen T. Gosnell, Jessica Kebebew, Electron Duh, Quan-Yang Clark, Orlo H. TI Medullary Thyroid Cancer: It is a pain in the neck? SO JOURNAL OF CANCER LA English DT Article DE Medullary thyroid cancer; lymph node; papillary thyroid cancer AB Background: Medullary thyroid cancer (MTC) commonly presents with lymph node (LN) metastases, and has a worse prognosis than papillary thyroid cancer (PTC). Tumor size and LN involvement have been shown to affect stage of disease; however, to our knowledge, ours is the first study that attempts to correlate anterior neck pain on presentation with the extent of disease. Methods: We performed a retrospective review of patients with MTC who underwent an operation from February 1998 through December 2008. We compared the symptom of anterior neck pain with the pathologic extent of disease. Our control group comprised patients who underwent an operation for PTC. Analysis was performed using the Fisher's exact test and the Mann-Whitney test. Results: Of the 109 patients with MTC, 50 (46%) met our inclusion criteria. Of the 50 patients with MTC, 11 presented with neck pain, compared to 3 of the 50 patients with PTC (p = 0.041). Of those 11 patients, 9 (82%) had LN involvement on final pathology, as compared with 14 (36%) of the 39 without neck pain (p = 0.014). Of patients with neck pain, 18% were diagnosed at stage I to II and 82% at stage III to IV, compared to 64% at stage I to II and 36% at stage III to IV (p = 0.014). Conclusions: Our study demonstrates that more patients with MTC present with anterior neck pain than do patients with PTC and that patients with MTC and neck pain have an increased risk of LN metastases. The results of this study suggest that MTC patients, who present with concomitant neck pain, should undergo a total thyroidectomy, prophylactic bilateral central neck dissection, and ipsilateral lateral neck dissection. C1 [Guerrero, Marlon A.] Univ Arizona, Dept Surg, Tucson, AZ 85721 USA. [Lindsay, Sheila; Suh, Insoo; Vriens, Menno R.; Shen, Wen T.; Gosnell, Jessica; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Khanafshar, Elham] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Kebebew, Electron] NCI, Surg Branch, Bethesda, MD 20892 USA. RP Guerrero, MA (reprint author), Univ Arizona, Dept Surg, Tucson, AZ 85721 USA. EM mguerrero@surgery.arizona.edu FU Friends of Endocrine; Helen and Sanford Diller Family Foundation; Jerrold Heller Family Foundation; Bell Charitable Foundation FX We would like to thank the Friends of Endocrine, Helen and Sanford Diller Family Foundation, the Jerrold Heller Family Foundation, Dr. and Mrs. Andrew S. Grove, and the Bell Charitable Foundation for their support. NR 11 TC 2 Z9 2 U1 1 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 200 EP 205 DI 10.7150/jca.2.200 PG 6 WC Oncology SC Oncology GA V28QM UT WOS:000208695300023 PM 21509150 ER PT J AU Bratslavsky, G Sanford, T Srinivasan, R Aprelikova, O Liu, J Quezado, M Merino, M Linehan, WM AF Bratslavsky, Gennady Sanford, Thomas Srinivasan, Ramaprasad Aprelikova, Olga Liu, Jack Quezado, Martha Merino, Maria Linehan, W. Marston TI Differential Genetic Expression in Large Versus Small Clear Cell Renal Cell Carcinoma: Results from Microarray Analysis SO JOURNAL OF CANCER LA English DT Article DE Renal cell carcinoma; tumor; size; microarray; kidney AB Purpose: Tumor growth and progression requires multiple steps and genetic alterations. The molecular events that occur as tumors increase in size are unknown. Patients with von Hippel-Lindau (VHL) provide a unique opportunity to study molecular alterations during tumor growth as these patients develop multiple bilateral renal tumors. To better characterize biologic events associated with tumor growth, we evaluated the alterations in gene expression in large versus small renal tumors removed from the same kidney of the same individuals. Experimental Design: We reviewed pathology reports from patients who underwent partial nephrectomies at the National Cancer Institute for multiple tumors. We identified 11 patients who fulfilled the following inclusion criteria: 1) The patient must have had a surgical resection of more than one solid tumor from the same kidney during the same operation; 2) Among the solid tumors at least one must have been greater than 3 cm in the largest dimension and at least one less than 2 cm; 3) the nuclear Furhman grade for both larger and smaller solid tumors was identical; 4) a portion of each tumor was procured and snap frozen after surgical removal; 5) Hematoxylin and eosin staining of the frozen sample confirmed clear cell carcinoma to be present in at least 80% of the section. Affymetrix platform and protocol for gene expression arrays were used. RNA from the frozen large and small tumor samples was extracted using Trizol-Chlorophorm method. The RNA was then reverse transcribed, labeled, fragmented, and hybridized on to an Affymetrix U133 Plus 2.0 array that contains 54,000 probe sets representing 24,568 genes. Analysis included unsupervised clustering and chromosomal analysis. The paired t-test was performed to compare gene expression levels in small and large tumors. P<0.01 was considered statistically significant. Results: Gene expression profiles were assessed for 22 tumors (11 patients). Upon unsupervised clustering the pairs with larger tumor volume difference clustered separately from pairs with smaller volume difference. Chromosomal analysis revealed few consistent changes other than reduced expression of chromosome 3p25 among all tumors. Paired t-test showed 860 differentially expressed genes in the T1b vs T1a group, a number far greater than expected due to chance alone. When analyzed by gene function, most differences were observed in genes involved in DNA replication and in cytokine signaling. Conclusions: This study demonstrates that as tumors increase in size there is an increasing difference in gene expression. Unsupervised clustering analysis confirms that as the volume difference increases there are a distinct set of genes that are regulated either as a response to a tumor's growth or as an early event that causes the tumor to grow. While we did not observe chromosomal instability, we did note differences in expression of individual transcripts as tumors grew larger. C1 [Bratslavsky, Gennady; Sanford, Thomas; Srinivasan, Ramaprasad; Liu, Jack; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Aprelikova, Olga] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Quezado, Martha; Merino, Maria] NCI, Surg Pathol Branch, NIH, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research NR 20 TC 2 Z9 2 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 271 EP 279 DI 10.7150/jca.2.271 PG 9 WC Oncology SC Oncology GA V28QM UT WOS:000208695300029 PM 21611108 ER PT J AU Xiang, XR Feng, MQ Felder, M Connor, JP Man, YG Patankar, MS Ho, M AF Xiang, Xinran Feng, Mingqian Felder, Mildred Connor, Joseph P. Man, Yan-gao Patankar, Manish S. Ho, Mitchell TI HN125: A Novel Immunoadhesin Targeting MUC16 with Potential for Cancer Therapy SO JOURNAL OF CANCER LA English DT Article DE immunoadhesin; human Fc fusion; mesothelin; mucin MUC16/CA125; antibody-dependent cellular cytotoxicity (ADCC); ovarian cancer; mesothelioma AB Background: The mucin MUC16 expresses the repeating peptide epitope CA125 that has been known for decades to be a well-validated cancer marker that is overexpressed on the cell surface of ovarian cancers and other malignant tumors. In spite of recent efforts to make mouse monoclonal antibodies to MUC16 to treat ovarian cancer, a human monoclonal antibody against this mucin has not been described. MUC16 interacts with mesothelin, a protein that mediates heterotypic cancer cell adhesion, indicating that MUC16 and mesothelin play an important role in the peritoneal implantation and metastasis of ovarian tumors. Therefore, a suitable candidate for therapeutic targeting of MUC16 would functionally block the interaction of MUC16 and mesothelin. Methodology/Principal Findings: Here we report the generation of a novel immunoadhesin, HN125, against MUC16 that consists of a functional MUC16 binding domain of mesothelin (IAB) and the Fc portion of a human antibody IgG1. The yield for purified HN125 proteins is over 100 mu g/mL of HEK-293 culture supernatant. We show that HN125 has high and specific affinity for MUC16-expressing cancer cells by flow cytometry and immunohistochemistry. HN125 has the ability to disrupt the heterotypic cancer cell adhesion mediated by the MUC16-mesothelin interaction. Moreover, it elicits strong antibody-dependent cell mediated cytotoxicity against MUC16-positive cancer cells in vitro. Conclusion/Significance: This report describes a novel human immunotherapeutic agent highly specific for MUC16 with potential for treating ovarian cancer and other MUC16-expressing tumors. Because of its lower immunogenicity in patients, a fully human protein is the most desirable format for clinical applications. We believe that the methods developed here may apply to the generation of other tumor-targeting immunoadhesins when it is difficult to obtain a human monoclonal antibody to a given antigen for clinical applications. The resultant immunoadhesins can have advantages usually found in monoclonal antibodies such as ease of purification, high binding affinity and effector functions. C1 [Xiang, Xinran; Feng, Mingqian; Ho, Mitchell] NCI, Antibody Therapy Unit, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Felder, Mildred; Connor, Joseph P.; Patankar, Manish S.] Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53792 USA. [Man, Yan-gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. [Man, Yan-gao] Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Washington, DC 20306 USA. RP Ho, M (reprint author), NCI, Antibody Therapy Unit, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA. EM homi@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU NIH, National Cancer Institute, Center for Cancer Research; Ovarian Cancer Research Fund Individual Investigator Award; Mesothelioma Applied Research Foundation; National Institutes of Health [1R41CA132520-01A2, 1R21CA143616-01] FX This work was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, in part by an Ovarian Cancer Research Fund Individual Investigator Award to MH, and in part by a Mesothelioma Applied Research Foundation Grant in Honor of Craig Kozicki to MH. This work was also possible because of the grants from the National Institutes of Health (1R41CA132520-01A2 and 1R21CA143616-01) to JPC and MSP. Dr. Mitchell Ho is a co-inventor on patents assigned to the United States of America, as represented by the Department of Health and Human Services, for the investigational products. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 48 TC 12 Z9 13 U1 1 U2 4 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 280 EP 291 DI 10.7150/jca.2.280 PG 12 WC Oncology SC Oncology GA V28QM UT WOS:000208695300030 PM 21611109 ER PT J AU Bregni, M Childs, RW Ueno, NT AF Bregni, Marco Childs, Richard W. Ueno, Naoto T. TI 4th Edition of the International Autologous and Allogeneic Cell Therapy for Solid Tumors (ATST) Meeting SO JOURNAL OF CANCER LA English DT Editorial Material DE Autologous and Allogeneic Cell Therapy; Solid Tumors AB The fourth edition of the International Autologous and Allogeneic Cell Therapy for Solid Tumors (ATST) meeting was held in Venice, Italy, between March 31 and April 1, 2011. C1 [Bregni, Marco] Ist Sci San Raffaele, Dept Hematol, Milan, Italy. [Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Ueno, Naoto T.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. RP Ueno, NT (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe,Unit 1354, Houston, TX 77030 USA. EM nueno@mdanderson.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 307 EP 308 DI 10.7150/jca.2.307 PG 2 WC Oncology SC Oncology GA V28QM UT WOS:000208695300033 PM 21716846 ER PT J AU Dudley, ME AF Dudley, Mark E. TI Adoptive Cell Therapy for Patients with Melanoma SO JOURNAL OF CANCER LA English DT Article DE TIL; melanoma; NY-ESO-1; interleukin-2; lymphodepletion AB Adoptive cell therapy can be an effective treatment for some patients with advanced cancer. This report summarizes clinical trial results from the Surgery Branch, NCI, investigating tumor infiltrating lymphocytes (TIL) and gene engineered peripheral blood T cells for the therapy of patients with melanoma and other solid tumors. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Dudley, ME (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 12 Z9 12 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 360 EP 362 DI 10.7150/jca.2.360 PG 3 WC Oncology SC Oncology GA V28QM UT WOS:000208695300045 PM 21716716 ER PT J AU Lundqvist, A Berg, M Smith, A Childs, RW AF Lundqvist, Andreas Berg, Maria Smith, Aleah Childs, Richard W. TI Bortezomib Treatment to Potentiate the Anti-tumor Immunity of Ex-vivo Expanded Adoptively Infused Autologous Natural Killer Cells SO JOURNAL OF CANCER LA English DT Article DE Bortezomib; Anti-tumor Immunity; Autologous Natural Killer Cells AB Our results show that using an EBV-LCL feeder cell line, large numbers of pure populations of highly activated NK cells can be expanded ex vivo under GMP conditions. With the exception of thyroiditis and constitutional symptoms related to IL-2 therapy, infusions of up to 1 x 10(8) cells/kg of ex vivo expanded NK have been well tolerated and have provided preliminary clinical evidence for mediating anti-tumor immunity in patients with advanced cancer. C1 [Lundqvist, Andreas] Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Stockholm, Sweden. [Berg, Maria; Smith, Aleah; Childs, Richard W.] NHLBI, Sect Transplantat Immunotherapy, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, Sect Transplantat Immunotherapy, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM childsr@mail.nih.gov OI Lundqvist, Andreas/0000-0002-9709-2970 FU NIH, National Heart, Lung, and Blood Institute, Hematology Branch; ACKC (Action to Cure Kidney Cancer) FX This work was supported by the intramural research program of NIH, National Heart, Lung, and Blood Institute, Hematology Branch. We wish to acknowledge the ACKC (Action to Cure Kidney Cancer) for their support of this research as well as the Dean R. O'Neill Memorial Fellowship for generous contributions supporting this research. NR 10 TC 35 Z9 36 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 383 EP 385 DI 10.7150/jca.2.383 PG 3 WC Oncology SC Oncology GA V28QM UT WOS:000208695300050 PM 21750690 ER PT J AU Phung, YT Barbone, D Broaddus, VC Ho, M AF Phung, Yen T. Barbone, Dario Broaddus, V. Courtney Ho, Mitchell TI Rapid Generation of In Vitro Multicellular Spheroids for the Study of Monoclonal Antibody Therapy SO JOURNAL OF CANCER LA English DT Article DE multicellular spheroids; protocol; monoclonal antibody therapy AB Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates and are difficult to study in vitro. Cells cultured as monolayers typically exhibit less resistance to therapy than those grown in vivo. Therefore, it is important to develop an alternative research model that better represents in vivo tumors. We have developed a protocol to produce multicellular spheroids, a simple and more relevant model of in vivo tumors that allows for further investigations of the microenvironmental effects on drug penetration and tumor cell killing. The protocol is used to produce in vitro three-dimensional tumor spheroids from established human cancer cell lines and primary cancer cells isolated from patients without the use of any extracellular components. To study the ability of tumor-targeting immunoconjugates to penetrate these tumor spheroids in vitro, we have used an immunotoxin targeting mesothelin, a surface protein expressed in malignant mesotheliomas. This method for producing consistent, reproducible 3D spheroids may allow for improved testing of novel monoclonal antibodies and other agents for their ability to penetrate solid tumors for cancer therapy. C1 [Phung, Yen T.; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Barbone, Dario; Broaddus, V. Courtney] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA. RP Ho, M (reprint author), NCI, Antibody Therapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA. RI Ho, Mitchell/F-5059-2015 FU Department of Defense [PR080717]; National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR); NCI FX This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research (CCR), and in part by the Department of Defense PR080717. Dr. Mitchell Ho is supported by the 2011 NCI Director's Intramural Innovation Award (Principal Investigator Award). Dr. Ho is a co-inventor on patents assigned to the United States of America, as represented by the Department of Health and Human Services, for the investigational products. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We thank the NIH Fellows Editorial Board for editorial assistance. NR 12 TC 24 Z9 24 U1 3 U2 5 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 507 EP 514 DI 10.7150/jca.2.507 PG 8 WC Oncology SC Oncology GA V28QM UT WOS:000208695300064 PM 22043235 ER PT J AU Valera, VA Walter, BA Linehan, WM Merino, MJ AF Valera, Vladimir A. Walter, Beatriz A. Linehan, W. Marston Merino, Maria J. TI Regulatory Effects of microRNA-92 (miR-92) on VHL Gene Expression and the Hypoxic Activation of miR-210 in Clear Cell Renal Cell Carcinoma SO JOURNAL OF CANCER LA English DT Article DE miRNA; VHL; RCC; ccRCC; BHD; HLRCC; TSC; BHD ID TUMOR HYPOXIA; KIDNEY CANCER; MOLECULAR CLASSIFICATION; EPITHELIAL NEOPLASMS; PROGNOSTIC-FACTOR; NECK-CANCER; MARKER; HSA-MIR-210; SIGNATURES; IMPACT AB Background & Aims: In order to understand the role of miRNAs in renal tumorigenesis, we undertook a stepwise approach that included a comprehensive differential miRNA expression analysis for the most common histological subtypes of human renal neoplasms appearing in either sporadic or hereditary forms. We also aimed to test the hypothesis that microRNAs can act as an alternative mechanism of VHL gene inactivation and therefore might be correlated with tumorigenesis in ccRCC. Finally, we wanted to explore whether the well-known hypoxic activation of ccRCC is followed by a specific pattern of miRNA expression. Methods: Tumor and normal adjacent kidney parenchyma from patients with RCC were tested for microRNA expression. Twenty cases of different histologies were used for profiling by PCR miRNA arrays. For validation, a separate cohort of samples used to test specifically miR92a expression and its involvement in VHL gene mRNA silencing. Finally, miR210 as a marker of hypoxia was evaluated. Expression values were correlated with important clinicopathologic features from the patients. Results: We identified unique miRNA expression signatures for each histologic subtype of kidney tumors. Expression values for downregulated miRNAs ranged from 0.3-fold (in VHL-clear cell RCC) up to 0.393 fold (in papillary type II (HLRCC) tumors). For the upregulated miRNAs, fold-changes ranged from 2.1 up to 290-fold. Specific patterns together with type-specific profiles were observed. Twenty-three miRNAs were found to be differentially expressed in both sporadic and VHL-dependent ccRCC. Sporadic clear cell tumors showed a unique pattern of 14-miRNA that were absent from the VHL-dependent tumors. These also showed 15 miRNAs specific to the hereditary type. Common miRNAs to both sporadic and hereditary forms included miR-92a and miR-210. For miR-92a, and a striking inverse correlation with VHL mRNA levels was found. For the hypoxia-regulated miR-210, clear cell tumors showed significantly higher expression levels when compared to tumor of non-clear cell histology (9.90-fold vs. 1.36, p<0.001). Conclusions: microRNA expression seems to be involved in every step of RCC pathogenesis: both as an element for tumor development as well as a consequence of or in response to the initial malignant transformation and part of tumor progression. Our data show consistent disregulation of miRNAs in human kidney cancer, some of which are potentially involved in critical gene silencing in RCC and others that are activated as part of the pathophysiological response in these tumors. C1 [Valera, Vladimir A.; Walter, Beatriz A.; Merino, Maria J.] NCI, Translat Surg Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Merino, MJ (reprint author), 10 Ctr Dr,Bldg 10 MSC Room 2B44, Bethesda, MD 20892 USA. EM mjmerino@mail.nih.gov NR 44 TC 32 Z9 35 U1 0 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2011 VL 2 BP 515 EP 526 DI 10.7150/jca.2.515 PG 12 WC Oncology SC Oncology GA V28QM UT WOS:000208695300065 PM 22043236 ER PT J AU Charong, N Patmasiriwat, P Zenklusen, JC AF Charong, Nurdina Patmasiriwat, Pimpicha Zenklusen, Jean Claude TI Localization and characterization of ST7 in cancer SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE ST7; Localization; Tumor suppressor gene; 7q31; SERPINE1; Survivin ID TUMOR-SUPPRESSOR GENES; SUBCELLULAR-LOCALIZATION; CHROMOSOME 7Q31; CELL-LINES; CYCLIN D1; TUMORIGENICITY; APHIDICOLIN; EXPRESSION; MUTATIONS; CARCINOMA AB ST7 has been proposed to be a tumor suppressor gene in the chromosome region 7q31.1-q31.2. In order to gain some insight into its role in cancer, the localization and verification of the ST7 expression levels were determined. Various types of ST7 expression vectors tagged with the sequences of GFP, YFP or V5 were created using a gateway cloning system and full-length ST7 cDNA isolated from a human adult brain cDNA library. Cell cycle synchronization was also performed to analyze the expression of endogenous ST7 and its potentially related genes at each stage of the cell cycle. Cytosolic ST7 expression in HCT-116, MCF-7 and PC-3 cancer cell lines was detected via the fluorescence signal of the fusion proteins. ST7 translocation from the cytoplasm to the nucleus has not been observed in any of the conditions assayed. A cell cycle synchronization study demonstrated that both ST7 and SERPINE1 were overexpressed when cells were arrested. Expression of these genes was found to be diminished when the cells re-entered cell division status. In addition, we also found that Survivin, MMP-13 and Cyclin D1 were differentially expressed during the cell cycle. Our findings suggest that ST7 mediates tumor suppression through the regulation of the genes involved in maintaining the cellular structure of the cell and involved in oncogenic pathways. C1 [Charong, Nurdina; Patmasiriwat, Pimpicha] Mahidol Univ, Fac Med Technol, Salaya, Nakhon Pathom, Thailand. [Charong, Nurdina; Zenklusen, Jean Claude] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Patmasiriwat, P (reprint author), Mahidol Univ, Fac Med Technol, Salaya, Nakhon Pathom, Thailand. EM mtppm@mahidol.ac.th; jz44m@nih.gov FU Commission on higher Education (CHE), Thailand; Royal Golden Jubilee (RGJ) [PHD/0259/2546]; Thailand Research Fund FX This work was supported by (1) the Commission on higher Education (CHE), Thailand, (2) the Royal Golden Jubilee (RGJ, Grant # PHD/0259/2546), Thailand Research Fund and (3) the institutional supports to JCZ (NIH, USA) and PP (Mahidol Univ., Thailand) under the Ph.D. cooperative plan to NC. NR 31 TC 4 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD JAN PY 2011 VL 137 IS 1 BP 89 EP 97 DI 10.1007/s00432-010-0863-2 PG 9 WC Oncology SC Oncology GA 700ZQ UT WOS:000285784500011 PM 20238225 ER PT J AU Shlipak, MG Lash, JP Yang, W Teal, V Keane, M Cappola, T Keller, C Jamerson, K Kusek, J Delafontaine, P He, JA Miller, ER Schreiber, M Go, AS AF Shlipak, Michael G. Lash, James P. Yang, Wei Teal, Valerie Keane, Martin Cappola, Tom Keller, Chris Jamerson, Kenneth Kusek, John Delafontaine, Patrice He, Jiang Miller, Edgar R., III Schreiber, Martin Go, Alan S. CA CRIC Investigators TI Symptoms Characteristic of Heart Failure Among CKD Patients Without Diagnosed Heart Failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Hemoglobin; glomerular filtration rate ID ACUTE MYOCARDIAL-INFARCTION; RENAL-INSUFFICIENCY; HEALTH-STATUS; CYSTATIN-C; SERUM CREATININE; KIDNEY-FUNCTION; RISK-FACTOR; INDIVIDUALS; DISEASE; PREDICTORS AB Background: Epidemiological studies typically diagnose heart failure (HF) at the time of hospitalization, and have not evaluated the prevalence of HF symptoms in CKD patients without a prior HF diagnosis. Methods and Results: We modified the Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms characteristic of HF (dyspnea, edema, and fatigue) among 2883 chronic kidney disease (CKD) patients without diagnosed heart failure in the Chronic Renal Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the impact of dyspnea, fatigue, and edema on physical, social, and emotional functions (scored 0 to 100). The median KCCQ score was 92, and 25% had KCCQ scores <75. Compared with cystatin C-based estimated glomerular filtration rate >50 mL . min . 1.73m(2) (reference), estimated glomerular filtration rate 40 to 50, 30 to 40, and <30 were independently associated with lower KCCQ scores ( <75); adjusted odds ratios and (95% CI): 1.38 (1.06-1.78), 1.39 (1.09-1.82), and 2.15 (1.54-3.00), respectively. Lower hemoglobin (Hb) levels also had independent associations with KCCQ <75: Hb >14 g/dL (reference), Mb 13 to 14 g/dL (1.03; 0.76-1.40), Hb 12 to 13 g/dL (1.41; 1.04-1.91), Mb 11 to 12 g/dL (1.56; 1.12-2.16); and Hb <1 g/dL (1.65; 1.15-2.37). Conclusion: CKD patients without diagnosed HF have a substantial burden of symptoms characteristic of HF, particularly among those with lower estimated glomerular filtration rate and hemoglobin levels. (J Cardiac Fail 2011;17:17-23) C1 [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94109 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lash, James P.] Univ Illinois, Dept Med, Chicago, IL USA. [Yang, Wei; Teal, Valerie] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Keane, Martin; Cappola, Tom] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Keller, Chris] Boise Kidney & Hypertens Inst, Boise, ID USA. [Jamerson, Kenneth] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Kusek, John] NIDDK, Bethesda, MD USA. [Delafontaine, Patrice; He, Jiang] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Miller, Edgar R., III] Johns Hopkins Univ, Sch Publ Hlth, Dept Med, Baltimore, MD USA. [Schreiber, Martin] Cleveland Clin, Dept Hypertens & Nephrol, Stongsville, OH USA. [Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St,111A1, San Francisco, CA 94109 USA. EM michael.shlipak@ucsf.edu RI Yang, Wei/A-9223-2009; OI Yang, Wei/0000-0001-8984-4389; Teal, Valerie/0000-0001-7116-5353; Delafontaine, Patrice/0000-0003-3744-3617 FU University of Pennsylvania [UL1 RR-024134]; Johns Hopkins University [UL1 RR-025005]; University of Maryland [M01 RR-16500]; Case Western Reserve University [UL1 RR-024989]; University of Michigan [M01 RR-000042, UL1 RR-024986]; University of Illinois at Chicago [UL1 RR-029879]; [R01 DK066488] FX Supported by M.S.'s R01 DK066488 award (principal investigator M.S.). In addition, we would like to acknowledge the CRIC GCRC and CTSA awards: University of Pennsylvania (UL1 RR-024134), Johns Hopkins University (UL1 RR-025005), University of Maryland (M01 RR-16500), Case Western Reserve University (UL1 RR-024989), University of Michigan (M01 RR-000042, UL1 RR-024986), and University of Illinois at Chicago (UL1 RR-029879). NR 19 TC 12 Z9 13 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2011 VL 17 IS 1 BP 17 EP 23 DI 10.1016/j.cardfail.2010.08.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709AK UT WOS:000286407300004 PM 21187260 ER PT J AU Pellegrini, M Claps, G Orlova, VV Barrios, F Dolci, S Geremia, R Rossi, P Rossi, G Arnold, B Chavakis, T Feigenbaum, L Sharan, SK Nussenzweig, A AF Pellegrini, Manuela Claps, Giuseppina Orlova, Valeria V. Barrios, Florencia Dolci, Susanna Geremia, Raffaele Rossi, Pellegrino Rossi, Gabriele Arnold, Bernd Chavakis, Triantafyllos Feigenbaum, Lionel Sharan, Shyam K. Nussenzweig, Andre TI Targeted JAM-C deletion in germ cells by Spo11-controlled Cre recombinase SO JOURNAL OF CELL SCIENCE LA English DT Article DE Cre recombinase; JAM-C; Meiosis; Nbs1; Spo11 ID ADHESION MOLECULE-C; NIJMEGEN BREAKAGE SYNDROME; MRE11 COMPLEX; DNA-DAMAGE; CHROMOSOME SYNAPSIS; TRANSGENIC MICE; DEFICIENT MICE; STEM-CELLS; MOUSE; EXPRESSION AB Meiosis is a crucial process for the production of functional gametes. However, the biological significance of many genes expressed during the meiotic phase remains poorly understood, mainly because of the lethal phenotypes of the knockout mice. Functional analysis of such genes using the conditional knockout approach is hindered by the lack of suitable Cre transgenic lines. We describe here the generation of transgenic mice expressing Cre recombinase under the control of the meiotic Spo11 gene. Using LacZ-R26(loxP) and EYFP-R26(loxP) reporter mice, we show the specific expression and activity of Cre during meiosis in males and females. Spo11(Cre) mice were then crossed with floxed Nbs1 and JAM-C mice to produce conditional knockouts. A strong reduction of Nbs1 and JAM-C protein levels was found in the testis. Although Nbs1-deleted mice developed minor gonadal abnormalities, JAM-C-knockout mice showed a spermiogenetic arrest, as previously described for the null mice. These results provide strong evidence that Spo11(Cre) transgenic mice represent a powerful tool for deleting genes of interest specifically in meiotic and/or in postmeiotic germ cells. C1 [Pellegrini, Manuela; Claps, Giuseppina; Barrios, Florencia; Dolci, Susanna; Geremia, Raffaele; Rossi, Pellegrino; Rossi, Gabriele] Univ Roma Tor Vergata, Dept Publ Hlth & Cellular Biol, I-00133 Rome, Italy. [Orlova, Valeria V.] Leiden Univ, Med Ctr, NL-2300 RC Leiden, Netherlands. [Arnold, Bernd] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Chavakis, Triantafyllos] Univ Dresden, Dept Med, D-01307 Dresden, Germany. [Chavakis, Triantafyllos] Univ Dresden, Inst Physiol, D-01307 Dresden, Germany. [Feigenbaum, Lionel] Sci Applicat Int Corp, Frederick, MD 21702 USA. [Sharan, Shyam K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Pellegrini, M (reprint author), Univ Roma Tor Vergata, Dept Publ Hlth & Cellular Biol, I-00133 Rome, Italy. EM manuelapellegrini@libero.it RI Orlova, Valeria/C-6065-2014; dolci, susanna/B-8363-2013; OI Orlova, Valeria/0000-0002-1169-2802; dolci, susanna/0000-0002-6864-3673; GEREMIA, Raffaele/0000-0001-9056-6603; ROSSI, PELLEGRINO/0000-0003-4796-327X FU Italian Association for Cancer Research (AIRC); Italian Ministry of University [200788TPYE_002]; National Institutes of Health (NIH_NCI) FX We thank Steve Jay, Fabio Lancia, Simonetta Pucci, Graziano Bonelli and Angela Catizone for technical assistance, Dirk G. de Rooij for helpful suggestions on the manuscript. We are greatful to Richard Hodes for providing the LacZ-R26loxP mice and to Giacomo Consalez for the EYFP-R26loxP mice. This work was supported by grants from the Italian Association for Cancer Research (AIRC), the Italian Ministry of University (Grant Prin 2007 200788TPYE_002) and by the Intramural Research Program of the National Institutes of Health (NIH_NCI). Deposited in PMC for release after 12 months. NR 51 TC 7 Z9 8 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2011 VL 124 IS 1 BP 91 EP 99 DI 10.1242/jcs.072959 PG 9 WC Cell Biology SC Cell Biology GA 693RF UT WOS:000285242200011 PM 21147852 ER PT J AU Sundborger, A Soderblom, C Vorontsova, O Evergren, E Hinshaw, JE Shupliakov, O AF Sundborger, Anna Soderblom, Cynthia Vorontsova, Olga Evergren, Emma Hinshaw, Jenny E. Shupliakov, Oleg TI An endophilin-dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling SO JOURNAL OF CELL SCIENCE LA English DT Article DE Synapse; Endophilin; Dynamin; Endocytosis ID MEDIATED ENDOCYTOSIS; BAR DOMAIN; NEUROTRANSMITTER RELEASE; MEMBRANE CURVATURE; SYNAPTOJANIN; SYNAPSES; PROTEINS; INTERSECTIN; MECHANISM; PITS AB Clathrin-mediated vesicle recycling in synapses is maintained by a unique set of endocytic proteins and interactions. We show that endophilin localizes in the vesicle pool at rest and in spirals at the necks of clathrin-coated pits (CCPs) during activity in lamprey synapses. Endophilin and dynamin colocalize at the base of the clathrin coat. Protein spirals composed of these proteins on lipid tubes in vitro have a pitch similar to the one observed at necks of CCPs in living synapses, and lipid tubules are thinner than those formed by dynamin alone. Tubulation efficiency and the amount of dynamin recruited to lipid tubes are dramatically increased in the presence of endophilin. Blocking the interactions of the endophilin SH3 domain in situ reduces dynamin accumulation at the neck and prevents the formation of elongated necks observed in the presence of GTP gamma S. Therefore, endophilin recruits dynamin to a restricted part of the CCP neck, forming a complex, which promotes budding of new synaptic vesicles. C1 [Hinshaw, Jenny E.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Sundborger, Anna; Soderblom, Cynthia; Vorontsova, Olga; Evergren, Emma; Shupliakov, Oleg] Karolinska Inst, DBRM, Dept Neurosci, S-17177 Stockholm, Sweden. RP Hinshaw, JE (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM jennyh@helix.nih.gov; oleg.shupliakov@ki.se RI Sundborger, Anna/J-6590-2014; OI Sundborger, Anna/0000-0003-4696-7543; Shupliakov, Oleg/0000-0001-5352-6848 FU Swedish Research Council [13473, 20587]; Linne Center for Developmental Biology and Regenerative Medicine; Wallenberg's Stiftelse and Hjarnfonden; NIDDK, NIH; KI-NIH; Fernstrom's Stiftelse FX This study was supported by the Swedish Research Council grants 13473 and 20587, Linne Center for Developmental Biology and Regenerative Medicine, Wallenberg's Stiftelse and Hjarnfonden (O.S.); Intramural NIDDK, NIH (J.E.H.). A.S. received stipends and support from KI-NIH exchange program and Fernstrom's Stiftelse. We thank V. Haucke for endophilin constructs, N. Tomilin for help with electron microscopy, Peter Low and Arndt Pechstein, Karolinska Institutet, for expert advice and comments, and Pampa Ray, NIH, for help with the purification of dynamin. Deposited in PMC for release after 12 months. NR 35 TC 49 Z9 50 U1 3 U2 15 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2011 VL 124 IS 1 BP 133 EP 143 DI 10.1242/jcs.072686 PG 11 WC Cell Biology SC Cell Biology GA 693RF UT WOS:000285242200015 PM 21172823 ER PT J AU Wang, ZF Leng, Y Tsai, LK Leeds, P Chuang, DM AF Wang, Zhifei Leng, Yan Tsai, Li-Kai Leeds, Peter Chuang, De-Maw TI Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; cerebral ischemia; histone deacetylase inhibitor; matrix metalloproteinase-9; valproic acid ID TISSUE-PLASMINOGEN ACTIVATOR; MATRIX METALLOPROTEINASES; MATRIX-METALLOPROTEINASE-9; STROKE; MICE AB Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is known to protect against cerebral ischemia. The effects of VPA on blood-brain barrier (BBB) disruption were investigated in rats subjected to transient middle cerebral artery occlusion (MCAO). Postischemic VPA treatment remarkably attenuated MCAO-induced BBB disruption and brain edema. Meanwhile, VPA significantly reduced MCAO-induced elevation of matrix metalloproteinase-9 (MMP-9), degradation of tight junction proteins, and nuclear translocation of nuclear factor-kappa B (NF-kappa B). Sodium butyrate, another HDAC inhibitor, mimicked these effects of VPA. Our findings suggest that BBB protection by VPA involves HDAC inhibition-mediated suppression of NF-kappa B activation, MMP-9 induction, and tight junction degradation. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 52-57; doi:10.1038/jcbfm.2010.195; published online 27 October 2010 C1 [Wang, Zhifei; Leng, Yan; Tsai, Li-Kai; Leeds, Peter; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Tsai, Li-Kai] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan. [Tsai, Li-Kai] Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan. [Tsai, Li-Kai] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov RI Wang, Zhifei/I-2787-2013; OI Tsai, Li-Kai/0000-0001-8420-6951 FU National Institute of Mental Health, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 15 TC 109 Z9 119 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2011 VL 31 IS 1 BP 52 EP 57 DI 10.1038/jcbfm.2010.195 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 702BX UT WOS:000285870700008 PM 20978517 ER PT J AU Xu, F Uh, J Brier, MR Hart, J Yezhuvath, US Gu, H Yang, YH Lu, HZ AF Xu, Feng Uh, Jinsoo Brier, Matthew R. Hart, John, Jr. Yezhuvath, Uma S. Gu, Hong Yang, Yihong Lu, Hanzhang TI The influence of carbon dioxide on brain activity and metabolism in conscious humans SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE carbon dioxide; cerebral metabolic rate of oxygen; electroencephalogram; functional connectivity MRI; hypercapnia ID CEREBRAL-BLOOD-FLOW; CALIBRATED FUNCTIONAL MRI; DEFAULT-MODE NETWORK; ECHO-PLANAR MRI; MOTOR CORTEX; SOMATOSENSORY STIMULATION; OXIDATIVE-METABOLISM; OXYGEN-CONSUMPTION; HYPERCAPNIA; FMRI AB A better understanding of carbon dioxide (CO(2)) effect on brain activity may have a profound impact on clinical studies using CO(2) manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO(2), via inhalation of 5% CO(2), may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO(2)) by 13.4% +/- 2.3% (N = 14) and, furthermore, the CMRO(2) change was proportional to the subject's end-tidal CO(2) (Et-CO(2)) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO(2) inhalation. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 58-67; doi:10.1038/jcbfm.2010.153; published online 15 September 2010 C1 [Xu, Feng; Uh, Jinsoo; Yezhuvath, Uma S.; Lu, Hanzhang] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA. [Brier, Matthew R.; Hart, John, Jr.] Univ Texas Dallas, Ctr BrainHlth, Dallas, TX 75230 USA. [Gu, Hong; Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA. RP Lu, HZ (reprint author), Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM hanzhang.lu@utsouthwestern.edu FU National Institutes of Health [R01 MH084021, R01 NS067015, R01 AG033106, R21 EB007821] FX This work was supported, in part, by the National Institutes of Health (Grants R01 MH084021, R01 NS067015, R01 AG033106, and R21 EB007821). NR 42 TC 93 Z9 94 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2011 VL 31 IS 1 BP 58 EP 67 DI 10.1038/jcbfm.2010.153 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 702BX UT WOS:000285870700009 PM 20842164 ER PT J AU Niwano, Y Saito, K Yoshizaki, F Kohno, M Ozawa, T AF Niwano, Yoshimi Saito, Keita Yoshizaki, Fumihiko Kohno, Masahiro Ozawa, Toshihiko TI Extensive screening for herbal extracts with potent antioxidant properties SO JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION LA English DT Review DE herbal extracts; scavenging activity; superoxide anions; hydroxyl radicals; antioxidant properties ID SCAVENGING ACTIVITY; SUPEROXIDE ANIONS; RESVERATROL AB This paper summarizes our research for herbal extracts with potent antioxidant activity obtained from a large scale screening based on superoxide radical (O-2(center dot-)) scavenging activity followed by characterization of antioxidant properties. Firstly, scavenging activity against O-2(center dot-) was extensively screened from ethanol extracts of approximately 1000 kinds of herbs by applying an electron spin resonance (ESR)-spin trapping method, and we chose four edible herbal extracts with prominently potent ability to scavenge O-2(center dot-). They are the extracts from Punica granatum (Peel), Syzygium aromaticum (Bud), Mangifera indica (Kernel), and Phyllanthus emblica (Fruit). These extracts were further examined to determine if they also scavenge hydroxyl radical (center dot OH), by applying the ESR spin-trapping method, and if they have heat resistance as a desirable characteristic feature. Experiments with the Fenton reaction and photolysis of H2O2 induced by UV irradiation demonstrated that all four extracts have potent ability to directly scavenge center dot OH. Furthermore, the scavenging activities against O-2(center dot-) and center dot OH of the extracts of P. granatum (peel), M. indica (kernel) and P. emblica (fruit) proved to be heat-resistant. The results of the review might give useful information when choosing a potent antioxidant as a foodstuff. For instance, the four herbal extracts chosen from extensive screening possess desirable antioxidant properties. In particular, the extracts of the aforementioned three herbs are expected to be suitable for food processing in which thermal devices are used, because of their heat resistance. C1 [Niwano, Yoshimi; Saito, Keita; Kohno, Masahiro; Ozawa, Toshihiko] Tohoku Univ, New Ind Creat Hatchery Ctr, Aoba Ku, Sendai, Miyagi 9808579, Japan. [Saito, Keita] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. [Yoshizaki, Fumihiko] Tohoku Pharmaceut Univ, Dept Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9818558, Japan. [Ozawa, Toshihiko] Yokohama Coll Pharm, Dept Hlth Pharm, Toduka Ku, Kanagawa 2450066, Japan. RP Niwano, Y (reprint author), Tohoku Univ, New Ind Creat Hatchery Ctr, Aoba Ku, 6-6-10 Aoba, Sendai, Miyagi 9808579, Japan. EM niwano@niche.tohoku.ac.jp; ozawa@rugbygoods.com NR 21 TC 7 Z9 13 U1 2 U2 6 PU JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION PI KYOTO PA KYOTO PREFECTURAL UNIV MED, GRAD SCH MEDICAL SCIENCE, DEPT MOLECULAR GASTROENTEROLOGY & HEPATOLOGY, KYOTO, 602-8566, JAPAN SN 0912-0009 EI 1880-5086 J9 J CLIN BIOCHEM NUTR JI J. Clin. Biochem. Nutr. PD JAN 1 PY 2011 VL 48 IS 1 BP 78 EP 84 DI 10.3164/jcbn.11-013FR PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 742YN UT WOS:000288981400014 PM 21297917 ER PT J AU Hershman, JM Cheng, SY Gianoukakis, AG AF Hershman, Jerome M. Cheng, Sheue-yann Gianoukakis, Andrew G. TI Update in Thyroidology 2010 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BRAF(V600E) MUTATION ANALYSIS; UNITED-STATES; INCREASING INCIDENCE; HORMONE RECEPTORS; CANCER; NODULES; OPHTHALMOPATHY; HYPOTHYROIDISM; PREVALENCE; SPECIMENS AB This has been an exciting year in thyroid research. In this article, we summarize the new developments in selected areas of thyroid research by reporting on key papers published during the period June 2009 to June 2010. We selected those papers that, in our opinion, have significant clinical or translational impact. Selection criteria were applied for inclusion of papers for the Year in Thyroid lecture at the 92nd Annual Meeting of The Endocrine Society in San Diego, June, 2010. Papers relating to translational and clinical discovery in thyroidology were reviewed. Papers were chosen if they provided new insight into the understanding of thyroid disease and advanced clinical science, or advanced the diagnosis of disease, or proposed new therapy, or provided new data on important clinical questions in thyroidology. Here we review and discuss these papers and show how they provide new insights into clinical thyroidology. (J Clin Endocrinol Metab 96: 9-14, 2011) C1 [Hershman, Jerome M.] W Los Angeles VA Med Ctr, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. [Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA. [Gianoukakis, Andrew G.] Harbor Univ Calif Los Angeles UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Hershman, Jerome M.; Gianoukakis, Andrew G.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Hershman, JM (reprint author), W Los Angeles VA Med Ctr, Endocrinol & Diabet Div, Endocrinolgy 111D, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 27 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP 9 EP 14 DI 10.1210/jc.2010-2350 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710HW UT WOS:000286502900002 PM 21209040 ER PT J AU Collins, MT Boehm, M AF Collins, Michael T. Boehm, Manfred TI It ANKH Necessarily So SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID ALKALINE-PHOSPHATASE; CRANIOMETAPHYSEAL DYSPLASIA; MUTATIONS; BONE; GENE; MINERALIZATION; CHONDROCALCINOSIS; HYPOPHOSPHATASIA; CALCIFICATION; ARTHRITIS C1 [Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Boehm, Manfred] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 17 TC 8 Z9 8 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP 72 EP 74 DI 10.1210/jc.2010-2614 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710HW UT WOS:000286502900014 PM 21209049 ER PT J AU Copeland, KC Zeitler, P Geffner, M Guandalini, C Higgins, J Hirst, K Kaufman, FR Linder, B Marcovina, S McGuigan, P Pyle, L Tamborlane, W Willi, S AF Copeland, Kenneth C. Zeitler, Philip Geffner, Mitchell Guandalini, Cindy Higgins, Janine Hirst, Kathryn Kaufman, Francine R. Linder, Barbara Marcovina, Santica McGuigan, Paul Pyle, Laura Tamborlane, William Willi, Steven CA TODAY Study Grp TI Characteristics of Adolescents and Youth with Recent-Onset Type 2 Diabetes: The TODAY Cohort at Baseline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FATTY LIVER; MELLITUS; CHILDREN; PREVALENCE; ASSOCIATION; AMERICAN; AMINOTRANSFERASE; COMPLICATIONS; SEARCH AB Context: The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort represents the largest and best-characterized national sample of American youth with recent-onset type 2 diabetes. Objective: The objective of the study was to describe the baseline characteristics of participants in the TODAY randomized clinical trial. Design: Participants were recruited over 4 yr at 15 clinical centers in the United States (n = 704) and enrolled, randomized, treated, and followed up 2-6 yr. Setting: The study was conducted at pediatric diabetes care clinics and practices. Participants: Eligible participants were aged 10-17 yr inclusive, diagnosed with type 2 diabetes for less than 2 yr and had a body mass index at the 85th percentile or greater. Interventions: After baseline data collection, participants were randomized to one of the folllowing groups: 1) metformin alone, 2) metformin plus rosiglitazone, or 3) metformin plus a lifestyle program of weight management. Main Outcome Measures: Baseline data presented include demographics, clinical/medical history, biochemical measurements, and clinical and biochemical abnormalities. Results: At baseline the cohort included the following: 64.9% were female; mean age was 14.0 yr; mean diabetes duration was 7.8 months; mean body mass index Z-score was 2.15; 89.4% had a family history of diabetes; 41.1% were Hispanic, 31.5% were non-Hispanic black; 38.8% were living with both biological parents; 41.5% had a household annual income of less than $25,000; 26.3% had a highest education level of parent/guardian less than a high school degree; 26.3% had a blood pressure at the 90th percentile or greater; 13.6% had a blood pressure at the 95th percentile or greater; 13.0% had microalbuminuria; 79.8% had a low high-density lipoprotein level; and 10.2% had high triglycerides. Conclusions: The TODAY cohort is predominantly from racial/ethnic minority groups, with low socio-economic status and a family history of diabetes. Clinical and biochemical abnormalities and comorbidities are prevalent within 2 yr of diagnosis. These findings contribute greatly to our understanding of American youth with type 2 diabetes. (J Clin Endocrinol Metab 96: 159-167, 2011) C1 [Copeland, Kenneth C.] Univ Oklahoma, Coll Med, Dept Pediat, Oklahoma City, OK 73104 USA. [Zeitler, Philip; Higgins, Janine] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA. [Geffner, Mitchell; Kaufman, Francine R.] Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Dept Pediat, Los Angeles, CA 90027 USA. [Guandalini, Cindy; Tamborlane, William] Yale Univ, Dept Pediat, New Haven, CT 06520 USA. [Hirst, Kathryn; Pyle, Laura] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. [Linder, Barbara] NIDDKD, NIH, Bethesda, MD 20892 USA. [Marcovina, Santica] Univ Washington, NW Lipid Metab & Diabet Res Labs, Seattle, WA 98109 USA. [McGuigan, Paul] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Willi, Steven] Univ Penn, Childrens Hosp Philadelphia, Dept Endocrinol & Diabet, Philadelphia, PA 19104 USA. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. RP Copeland, KC (reprint author), Univ Oklahoma, Coll Med, Dept Pediat, 1200 N Phillips,Suite 4500, Oklahoma City, OK 73104 USA. EM kenneth-copeland@ouhsc.edu OI Zeitler, Philip/0000-0001-5756-7858 FU Becton, Dickinson and Co.; Bristol-Myers Squibb; Eli Lilly and Co.; GlaxoSmithKline; LifeScan, Inc.; Pfizer; Sanofi-Aventis; National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health [U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, U01-DK61254]; National Center for Research Resources General Clinical Research Center (Washington University School of Medicine) [M01-RR00036]; National Center for Research Resources General Clinical Research Center (Childrens Hospital Los Angeles) [M01-RR00043-45]; National Center for Research Resources General Clinical Research Center (University of Colorado Denver) [M01-RR00069]; National Center for Research Resources General Clinical Research Center (Children's Hospital of Pittsburgh) [M01-RR00084]; National Center for Research Resources General Clinical Research Center (Massachusetts General Hospital) [M01-RR01066]; National Center for Research Resources General Clinical Research Center (Yale University) [M01-RR00125]; National Center for Research Resources General Clinical Research Center (University of Oklahoma Health Sciences Center) [M01-RR14467]; National Center for Research Resources Clinical and Translational Science (Children's Hospital of Philadelphia) [UL1-RR024134]; National Center for Research Resources Clinical and Translational Science (Yale University) [UL1-RR024139]; National Center for Research Resources Clinical and Translational Science (Children's Hospital of Pittsburgh) [UL1-RR024153]; National Center for Research Resources Clinical and Translational Science (Case Western Reserve University) [UL1-RR024989]; National Center for Research Resources Clinical and Translational Science (Washington University) [UL1-RR024992]; National Center for Research Resources Clinical and Translational Science (Massachusetts General Hospital) [UL1-RR025758]; National Center for Research Resources Clinical and Translational Science (University of Colorado Denver) [UL1-RR025780] FX The TODAY Study Group thanks the American Diabetes Association and the following companies for donations in support of the study's efforts: Becton, Dickinson and Co.; Bristol-Myers Squibb; Eli Lilly and Co.; GlaxoSmithKline; LifeScan, Inc.; Pfizer; and Sanofi-Aventis.; This work was completed with funding from National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health Grants U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254; the National Center for Research Resources General Clinical Research Centers Program Grants M01-RR00036 (Washington University School of Medicine), M01-RR00043-45 (Childrens Hospital Los Angeles), M01-RR00069 (University of Colorado Denver), M01-RR00084 (Children's Hospital of Pittsburgh), M01-RR01066 (Massachusetts General Hospital), M01-RR00125 (Yale University), and M01-RR14467 (University of Oklahoma Health Sciences Center); and the National Center for Research Resources Clinical and Translational Science Awards Grants UL1-RR024134 (Children's Hospital of Philadelphia), UL1-RR024139 (Yale University), UL1-RR024153 (Children's Hospital of Pittsburgh), UL1-RR024989 (Case Western Reserve University), UL1-RR024992 (Washington University), UL1-RR025758 (Massachusetts General Hospital), and UL1-RR025780 (University of Colorado Denver). NR 25 TC 106 Z9 108 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP 159 EP 167 DI 10.1210/jc.2010-1642 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 710HW UT WOS:000286502900025 PM 20962021 ER PT J AU Faucz, FR Horvath, A Rothenbuhler, A Almeida, MQ Libe, R Raffin-Sanson, ML Bertherat, J Carraro, DM Soares, FA Molina, GD Campos, AH Alexandre, RB Bendhack, ML Nesterova, M Stratakis, CA AF Faucz, Fabio Rueda Horvath, Anelia Rothenbuhler, Anya Almeida, Madson Q. Libe, Rossella Raffin-Sanson, Marie-Laure Bertherat, Jerome Carraro, Dirce Maria Soares, Fernando Augusto Molina, Gustavo de Campos Campos, Antonio H. Alexandre, Rodrigo B. Bendhack, Marcelo Luiz Nesterova, Maria Stratakis, Constantine A. TI Phosphodiesterase 11A (PDE11A) Genetic Variants May Increase Susceptibility to Prostatic Cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GENOME-WIDE ASSOCIATION; MUTATIONS; IDENTIFICATION; HYPERPLASIA; TUMORS; LOCI AB Context: Among the genomic loci harboring potential candidate genes for prostatic cancer (PCa) is the 2q31-33 chromosomal region that harbors the gene encoding phosphodiesterase 11A (PDE11A). In addition, the combined cancer genome expression metaanalysis datasets included PDE11A among the top 1% down-regulated genes in PCa. Objective: In the present study, we screened 50 unrelated PCa patients of Brazilian descent for PDE11A coding defects. Design: The study consisted of PDE11A sequencing, in vitro functional assays, and immunostaining analysis. Results: We identified eight different sequence alterations in 15 patients (30%): one stop-codon and seven missense mutations. Three of the variants (R202C, Y658C, and E840K) were novel, and the remaining five (Y727C, R804H, R867G, M878V, and R307X) have been associated with predisposition to adrenal or testicular tumors. The overall prevalence of PDE11A-inactivating sequence variants among PCa patients was significantly higher than in 287 healthy controls (0.16 vs. 0.051, respectively, P < 0.001, odds ratio 3.81, 95% confidence interval 1.86-7.81) and the R202C, Y658C, and E840K substitutions were not found in controls. All missense mutations led to decreased PDE11A activity in human embryonic kidney 293 and PC3M cells and immunostaining of PCa samples with sequence changes showed decreased PDE11A protein expression. Conclusion: Our data suggest that, like in the adrenal cortex and the testicular germ cells, PDE11A-inactivating genetic alterations may play a role in susceptibility to PCa. (J Clin Endocrinol Metab 96: E135-E140, 2011) C1 [Faucz, Fabio Rueda; Alexandre, Rodrigo B.; Bendhack, Marcelo Luiz] Pontificia Univ Catolica Parana, Mol Genet Lab, Grp Adv Mol Invest, Grad Program Hlth Sci, BR-80215901 Curitiba, Parana, Brazil. [Faucz, Fabio Rueda; Horvath, Anelia; Rothenbuhler, Anya; Almeida, Madson Q.; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol Genet, NIH, Bethesda, MD 20892 USA. [Rothenbuhler, Anya; Libe, Rossella; Raffin-Sanson, Marie-Laure; Bertherat, Jerome] Univ Paris 05, Dept Endocrinol Metab & Canc, Inst Natl Sante & Rech Med Unite 1016, CNRS,Inst Cochin,Unite Mixte Rech 8104, F-75014 Paris, France. [Raffin-Sanson, Marie-Laure] Univ Versailles, F-92210 St Quentin en Yvelines, France. [Carraro, Dirce Maria; Soares, Fernando Augusto; Molina, Gustavo de Campos] AC Camargo Hosp, Lab Genom & Mol Biol, BR-01509010 Sao Paulo, Brazil. [Campos, Antonio H.] AC Camargo Hosp, Dept Pathol, BR-01509010 Sao Paulo, Brazil. RP Faucz, FR (reprint author), Pontificia Univ Catolica Parana, Mol Genet Lab, Grp Adv Mol Invest, Grad Program Hlth Sci, Rua Imaculada Conceicao 1155, BR-80215901 Curitiba, Parana, Brazil. EM fabio.faucz@pucpr.br RI de Alexandre, Rodrigo/H-9489-2013; Oncogenomica, Inct/H-9999-2013; carraro, dirce/C-9179-2009; Campos, Antonio/C-9943-2012; OI de Alexandre, Rodrigo/0000-0002-1253-7716; carraro, dirce/0000-0001-5667-1418; Campos, Antonio/0000-0001-5322-7549; Soares, Fernando Augusto/0000-0003-1647-7842 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural National Institutes of Health [Z01-HD-000642-04]; Secretaria de Estado, da Ciencia, Tecnologia e Ensino Superior/Unidade Gestora do Fundo Parana (SETI/UGF) [098/07] FX This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural National Institutes of Health Project Z01-HD-000642-04 (to C.A.S.); and, in part, by a grant from the Secretaria de Estado, da Ciencia, Tecnologia e Ensino Superior/Unidade Gestora do Fundo Parana (SETI/UGF), Project 098/07 (to F.R.F.). NR 19 TC 13 Z9 13 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP E135 EP E140 DI 10.1210/jc.2010-1655 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 732LB UT WOS:000288185400019 PM 20881257 ER PT J AU Finkielstain, GP Chen, W Mehta, SP Fujimura, FK Hanna, RM Van Ryzin, C McDonnell, NB Merke, DP AF Finkielstain, Gabriela P. Chen, Wuyan Mehta, Sneha P. Fujimura, Frank K. Hanna, Reem M. Van Ryzin, Carol McDonnell, Nazli B. Merke, Deborah P. TI Comprehensive Genetic Analysis of 182 Unrelated Families with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RP-C4-CYP21-TNX RCCX MODULES; COPY-NUMBER VARIATIONS; CYP21 GENE; FUNCTIONAL-CHARACTERIZATION; DISEASE MANIFESTATION; MUTATIONAL SPECTRUM; MOLECULAR GENOTYPE; MISSENSE MUTATIONS; POINT MUTATIONS; MUTATED ALLELES AB Background: Genetic analysis is commonly performed in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Study Objective: The objective of the study was to describe comprehensive CYP21A2 mutation analysis in a large cohort of CAH patients. Methods: Targeted CYP21A2 mutation analysis was performed in 213 patients and 232 parents from 182 unrelated families. Complete exons of CYP21A2 were sequenced in patients in whom positive mutations were not identified by targeted mutation analysis. Copy number variation and deletions were determined using Southern blot analysis and PCR methods. Genotype was correlated with phenotype. Results: In our heterogeneous U.S. cohort, targeted CYP21A2 mutation analysis did not identify mutations on one allele in 19 probands (10.4%). Sequencing identified six novel mutations (p.Gln262fs, IVS8+1G > A, IVS9-1G > A, p.R408H, p.Gly424fs, p.R426P) and nine previously reported rare mutations. The majority of patients (79%) were compound heterozygotes and 69% of nonclassic (NC) patients were compound heterozygous for a classic and a NC mutation. Duplicated CYP21A2 haplotypes, de novo mutations and uniparental disomy were present in 2.7% of probands and 1.9 and 0.9% of patients from informative families, respectively. Genotype accurately predicted phenotype in 90.5, 85.1, and 97.8% of patients with salt-wasting, simple virilizing, and NC mutations, respectively. Conclusions: Extensive genetic analysis beyond targeted CYP21A2 mutational detection is often required to accurately determine genotype in patients with CAH due to the high frequency of complex genetic variation. (J Clin Endocrinol Metab 96: E161-E172, 2011) C1 [Finkielstain, Gabriela P.; Merke, Deborah P.] NIH, Program Dev Endocrinol & Genet, CRC, Bethesda, MD 20892 USA. [Mehta, Sneha P.; Hanna, Reem M.; Van Ryzin, Carol; Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Clin, Bethesda, MD 20892 USA. [Chen, Wuyan] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. [McDonnell, Nazli B.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Fujimura, Frank K.] Esoterix Inc, Calabasas, CA 91301 USA. RP Merke, DP (reprint author), NIH, Program Dev Endocrinol & Genet, CRC, Bldg 10,Room 1-2740,10 Ctr Dr,MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Aging; National Institutes of Health Clinical Center; Congenital Adrenal Hyperplasia Research, Education and Support Foundation; Phoqus Pharmaceuticals FX This work was supported by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Aging, and the National Institutes of Health Clinical Center, and (in part) by the Congenital Adrenal Hyperplasia Research, Education and Support Foundation. D.P.M. is a Commissioned Officer in the United States Public Health Service.; G.P.F., W.C., S.P.M., R.M.H., C.V.R., and N.B.M. have nothing to declare. F.K.F. is an employee of Esoterix, Inc., which performs clinical testing for CAH. D.P.M. received research funding from Phoqus Pharmaceuticals during 2007-2008. NR 53 TC 53 Z9 55 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP E161 EP E172 DI 10.1210/jc.2010-0319 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 732LB UT WOS:000288185400023 PM 20926536 ER PT J AU Libe, R Horvath, A Vezzosi, D Fratticci, A Coste, J Perlemoine, K Ragazzon, B Guillaud-Bataille, M Groussin, L Clauser, E Raffin-Sanson, ML Siegel, J Moran, J Drori-Herishanu, L Faucz, FR Lodish, M Nesterova, M Bertagna, X Bertherat, J Stratakis, CA AF Libe, Rossella Horvath, Anelia Vezzosi, Delphine Fratticci, Amato Coste, Joel Perlemoine, Karine Ragazzon, Bruno Guillaud-Bataille, Marine Groussin, Lionel Clauser, Eric Raffin-Sanson, Marie-Laure Siegel, Jennifer Moran, Jason Drori-Herishanu, Limor Faucz, Fabio Rueda Lodish, Maya Nesterova, Maria Bertagna, Xavier Bertherat, Jerome Stratakis, Constantine A. TI Frequent Phosphodiesterase 11A Gene (PDE11A) Defects in Patients with Carney Complex (CNC) Caused by PRKAR1A Mutations: PDE11A May Contribute to Adrenal and Testicular Tumors in CNC as a Modifier of the Phenotype SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GERM-CELL TUMORS; REGULATORY SUBUNIT; CYSTIC-FIBROSIS; VARIANTS; HYPERPLASIA; DISEASE; HUMANS; MICE AB Background: Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. Objectives: Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC. Results: A higher frequency of PDE11 A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P < 0.0001). Among CNC patients, those with PPNAD were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P < 0.001). A higher frequency of PDE11A sequence variants was also found in patients with large-cell calcifying Sertoli cell tumors (LCCSCT) compared with those without LCCSCT (50 vs. 10%, P = 0.0056). PDE11 A variants were significantly associated with the copresence of PPNAD and LCCSCT in men: 81 vs. 20%, P < 0.004). The simultaneous inactivation of PRKAR1A and PDE11A by small inhibitory RNA led to an increase in cAMP-regulatory element-mediated transcriptional activity under basal conditions and after stimulation by forskolin. Conclusions: We demonstrate, in a large cohort of CNC patients, a high frequency of PDE11A variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation. (J Clin Endocrinol Metab 96: E208-E214, 2011) C1 [Bertherat, Jerome] Hop Cochin, Assistance Publ Hop Paris, Serv Malad Endocriniennes & Metab, Reference Ctr Rare Adrenal Dis,Dept Endocrinol, F-75014 Paris, France. [Libe, Rossella; Vezzosi, Delphine; Fratticci, Amato; Perlemoine, Karine; Ragazzon, Bruno; Groussin, Lionel; Bertagna, Xavier; Bertherat, Jerome] Inst Cochin, Inst Natl Sante, Ctr Natl Rech Sci, Unite Mixte Rech 8104, F-8104 Paris, France. [Libe, Rossella; Vezzosi, Delphine; Fratticci, Amato; Perlemoine, Karine; Ragazzon, Bruno; Groussin, Lionel; Bertagna, Xavier; Bertherat, Jerome] Rech Med Unite 1016, F-8104 Paris, France. [Libe, Rossella; Vezzosi, Delphine; Fratticci, Amato; Perlemoine, Karine; Ragazzon, Bruno; Groussin, Lionel; Bertagna, Xavier; Bertherat, Jerome] Univ Paris 05, Paris, France. [Horvath, Anelia; Coste, Joel; Moran, Jason; Drori-Herishanu, Limor; Faucz, Fabio Rueda; Lodish, Maya; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Coste, Joel] Hop Cochin, Assistance Publ Hop Paris, Dept Biostat, F-75014 Paris, France. [Guillaud-Bataille, Marine; Clauser, Eric] Hop Cochin, Assistance Publ Hop Paris, Oncogenet Unit, F-75014 Paris, France. [Raffin-Sanson, Marie-Laure] Hop Ambroise Pare, Assistance Publ Hop Paris, Dept Endocrinol, F-92210 Boulogne Billancourt, France. [Faucz, Fabio Rueda] Pontificia Univ Catolica Parana, Mol Genet Lab, BR-80215901 Curitiba, Parana, Brazil. [Faucz, Fabio Rueda] Univ Versaille St Quentine, F-92210 Versailles, France. RP Bertherat, J (reprint author), Hop Cochin, Assistance Publ Hop Paris, Serv Malad Endocriniennes & Metab, Reference Ctr Rare Adrenal Dis,Dept Endocrinol, Pavil Cornil 27,Rue Faubourg St Jacques, F-75014 Paris, France. EM jerome.bertherat@cch.aphp.fr RI Ragazzon, Bruno/E-6541-2017 OI Ragazzon, Bruno/0000-0001-9476-4973 FU Agence Nationale pour la Recherche [ANR06-MRAR-007, ANR08-GENOPAT-002]; National Institute of Child Health and Human Development, intramural National Institutes of Health (NIH) [Z01-HD-000642-04]; NIH Clinical Center FX This work was supported by grants from the Agence Nationale pour la Recherche (ANR06-MRAR-007 and ANR08-GENOPAT-002) and, in part, by the National Institute of Child Health and Human Development, intramural National Institutes of Health (NIH) project Z01-HD-000642-04 to C.S., and, in part, by the NIH Clinical Center. NR 21 TC 35 Z9 40 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2011 VL 96 IS 1 BP E208 EP E214 DI 10.1210/jc.2010-1704 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 732LB UT WOS:000288185400028 PM 21047926 ER PT J AU Lo, B Lenardo, MJ AF Lo, Bernice Lenardo, Michael J. TI Gene defects in the soma: some get it and some don't! SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; FAS MUTATIONS; T-CELLS; LPR; APOPTOSIS; LEUKEMIA; ANTIGEN; MICE AB Advances in DNA sequencing technologies have increased attention on genetic variation in somatic tissues Although long known to cause neoplasm diseases, somatic variation is now being investigated as a pathogenetic mechanism for other diseases Somatic changes are genomic DNA variations that were not inherited but arise in tissues throughout life In this issue of the JCI, Magerus-Chatinet et al explore somatic changes in patients with autoimmune lymphoproliferative syndrome (ALPS), a congenital disease of defective apoptosis and autoimmunity that is usually associated with germline heterozygous mutations in the gene encoding the Fas death receptor They explain why certain individuals have severe disease manifestations by documenting somatic alterations in the germline normal FAS allele in an unusual population of "double-negative" T cells found in ALPS Thus, the oncological concept of somatic loss of heterozygosity leading to selected cell expansion also applies to autoimmune diseases C1 [Lo, Bernice; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. OI Lo, Bernice/0000-0002-1087-6845 FU Intramural NIH HHS NR 19 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2011 VL 121 IS 1 BP 16 EP 19 DI 10.1172/JCI45664 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 702KF UT WOS:000285892300005 PM 21183786 ER PT J AU Wang, R Khan, BA Cheung, GYC Bach, THL Jameson-Lee, M Kong, KF Queck, SY Otto, M AF Wang, Rong Khan, Burhan A. Cheung, Gordon Y. C. Bach, Thanh-Huy L. Jameson-Lee, Max Kong, Kok-Fai Queck, Shu Y. Otto, Michael TI Staphylococcus epidermidis surfactant peptides promote biofilm maturation and dissemination of biofilm-associated infection in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; PHENOL-SOLUBLE MODULINS; QUORUM-SENSING CONTROL; PSEUDOMONAS-AERUGINOSA; BACILLUS-SUBTILIS; GENE-EXPRESSION; IMMUNE EVASION; IN-VIVO; VIRULENCE; AUREUS AB Biofilms are surface-attached agglomerations of microorganisms embedded in an extracellular matrix Biofilm-associated infections are difficult to eradicate and represent a significant reservoir for disseminating and recurring serious infections Infections involving biofilms frequently develop on indwelling medical devices in hospitalized patients, and Staphylococcus epidermidis is the leading cause of infection in this setting However, the molecular determinants of biofilm dissemination are unknown Here we have demonstrated that specific secreted, surfactant-like S epidermidis peptides - the beta subclass of phenol-soluble modulins (PSMs) - promote S epidermidis biofilm structuring and detachment in vitro and dissemination from colonized catheters in a mouse model of device-related infection Our study establishes in vivo significance of biofilm detachment mechanisms for the systemic spread of biofilm-associated infection and identifies the effectors of biofilm maturation and detachment in a premier biofilm-forming pathogen Furthermore, by demonstrating that antibodies against PSM beta peptides inhibited bacterial spread from indwelling medical devices, we have provided proof of principle that interfering with biofilm detachment mechanisms may prevent dissemination of biofilm-associated infection C1 [Wang, Rong; Khan, Burhan A.; Cheung, Gordon Y. C.; Bach, Thanh-Huy L.; Jameson-Lee, Max; Kong, Kok-Fai; Queck, Shu Y.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike,Bldg 33 1W10, Bethesda, MD 20892 USA. RI Cheung, Yiu Chong /K-3565-2012; OI Otto, Michael/0000-0002-2222-4115 FU National Institute of Allergy and Infectious Diseases (NIAID), NIH FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), NIH The authors thank Frank DeLeo for critically reading the manuscript, Saravanan Periasamy, NIAID, for help with confocal microscopy, and Daniel C S Tan, Nanyang Polytechnic, Singa pore, for technical assistance NR 44 TC 97 Z9 98 U1 1 U2 25 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2011 VL 121 IS 1 BP 238 EP 248 DI 10.1172/JCI42520 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 702KF UT WOS:000285892300028 PM 21135501 ER PT J AU Fink, DL Fahle, GA Fischer, S Fedorko, DF Nutman, TB AF Fink, Doran L. Fahle, Gary A. Fischer, Steven Fedorko, Daniel F. Nutman, Thomas B. TI Toward Molecular Parasitologic Diagnosis: Enhanced Diagnostic Sensitivity for Filarial Infections in Mobile Populations SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; ONCHOCERCA-VOLVULUS INFECTION; REAL-TIME PCR; WUCHERERIA-BANCROFTI INFECTION; BRUGIA-MALAYI; LOA-LOA; REACTION ASSAY; BLOOD-SAMPLES; DNA; ELISA AB The diagnosis of filarial infections among individuals residing in areas where the disease is not endemic requires both strong clinical suspicion and expert training in infrequently practiced parasitological methods. Recently developed filarial molecular diagnostic assays are highly sensitive and specific but have limited availability and have not been closely evaluated for clinical use outside populations residing in areas of endemicity. In this study, we assessed the performance of a panel of real-time PCR assays for the four most common human filarial pathogens among blood and tissue samples collected from a cohort of patients undergoing evaluation for suspected filarial infections. Compared to blood filtration, real-time PCR was equally sensitive for the detection of microfilaremia due to Wuchereria bancrofti (2 of 46 samples positive by both blood filtration and PCR with no discordant results) and Loa loa (24 of 208 samples positive by both blood filtration and PCR, 4 samples positive by PCR only, and 3 samples positive by blood filtration only). Real-time PCR of skin snip samples was significantly more sensitive than microscopic examination for the detection of Onchocerca volvulus microfiladermia (2 of 218 samples positive by both microscopy and PCR and 12 samples positive by PCR only). The molecular assays required smaller amounts of blood and tissue than conventional methods and could be performed by laboratory personnel without specialized parasitology training. Taken together, these data demonstrate the utility of the molecular diagnosis of filarial infections in mobile populations. C1 [Fink, Doran L.; Nutman, Thomas B.] NIAID, LPD, NIH, Bethesda, MD 20892 USA. [Fahle, Gary A.; Fischer, Steven; Fedorko, Daniel F.] NIH, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIAID, LPD, NIH, 4 Ctr Dr,Room B1-03, Bethesda, MD 20892 USA. EM tnutman@niaid.nih.gov FU NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. NR 32 TC 27 Z9 27 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2011 VL 49 IS 1 BP 42 EP 47 DI 10.1128/JCM.01697-10 PG 6 WC Microbiology SC Microbiology GA 701AQ UT WOS:000285787100004 PM 20980560 ER PT J AU Duggan, C Irwin, ML Xiao, LR Henderson, KD Smith, AW Baumgartner, RN Baumgartner, KB Bernstein, L Ballard-Barbash, R McTiernan, A AF Duggan, Catherine Irwin, Melinda L. Xiao, Liren Henderson, Katherine D. Smith, Ashley Wilder Baumgartner, Richard N. Baumgartner, Kathy B. Bernstein, Leslie Ballard-Barbash, Rachel McTiernan, Anne TI Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BODY-MASS INDEX; PLASMA ADIPONECTIN; SERUM ADIPONECTIN; POSTMENOPAUSAL WOMEN; PROSPECTIVE COHORT; DIABETIC-PATIENTS; ANOREXIA-NERVOSA; RISK; METFORMIN; OBESITY AB Purpose Overweight or obese breast cancer patients have a worse prognosis compared with normal-weight patients. This may be attributed to hyperinsulinemia and dysregulation of adipokine levels associated with overweight and obesity. Here, we evaluate whether low levels of adiponectin and a greater level of insulin resistance are associated with breast cancer mortality and all-cause mortality. Patients and Methods We measured glucose, insulin, and adiponectin levels in fasting serum samples from 527 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer. We evaluated the association between adiponectin and insulin and glucose levels (expressed as the Homeostatic Model Assessment [HOMA] score) represented as continuous measures and median split categories, along with breast cancer mortality and all-cause mortality, using Cox proportional hazards models. Results Increasing HOMA scores were associated with reduced breast cancer survival (hazard ratio [HR], 1.12; 95% CI, 1.05 to 1.20) and reduced all-cause survival (HR, 1.09; 95% CI, 1.02 to 1.15) after adjustment for possible confounders. Higher levels of adiponectin (above the median: 15.5 mu g/mL) were associated with longer breast cancer survival (HR, 0.39; 95% CI, 0.15 to 0.95) after adjustment for covariates. A continuous measure of adiponectin was not associated with either breast cancer-specific or all-cause mortality. Conclusion Elevated HOMA scores and low levels of adiponectin, both associated with obesity, were associated with increased breast cancer mortality. To the best of our knowledge, this is the first demonstration of the association between low levels of adiponectin and increased breast cancer mortality in breast cancer survivors. C1 [Duggan, Catherine] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Yale Sch Publ Hlth, New Haven, CT USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NCI, Bethesda, MD 20892 USA. Univ Louisville, Sch Publ Hlth & Informat Sci, Louisville, KY 40292 USA. RP Duggan, C (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MD-B306, Seattle, WA 98104 USA. EM cduggan@fhcrc.org RI Duggan, Catherine/F-9414-2015 OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010, U54-CA116847, U54CA116848, R25-CA94880]; National Institutes of Health; University of New Mexico [NCRR M01-RR-0997]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528]; [M01-RR-00037] FX Supported by Grants No. N01-CN-75036-20, N01-CN-05228, N01-PC-67010, U54-CA116847, U54CA116848, and R25-CA94880 from the National Cancer Institute; M01-RR-00037 from the National Institutes of Health; NCRR M01-RR-0997 from the University of New Mexico; N01-HD-3-3175 from the National Institute of Child Health and Human Development; and 050Q-8709-S1528 from the California Department of Health Services. NR 59 TC 110 Z9 112 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2011 VL 29 IS 1 BP 32 EP 39 DI 10.1200/JCO.2009.26.4473 PG 8 WC Oncology SC Oncology GA 700DB UT WOS:000285712400017 PM 21115858 ER PT J AU Irwin, ML Duggan, C Wang, CY Smith, AW McTiernan, A Baumgartner, RN Baumgartner, KB Bernstein, L Ballard-Barbash, R AF Irwin, Melinda L. Duggan, Catherine Wang, Ching-Yun Smith, Ashley Wilder McTiernan, Anne Baumgartner, Richard N. Baumgartner, Kathy B. Bernstein, Leslie Ballard-Barbash, Rachel TI Fasting C-Peptide Levels and Death Resulting From All Causes and Breast Cancer: The Health, Eating, Activity, and Lifestyle Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR-I; PHYSICAL-ACTIVITY LEVELS; POSTMENOPAUSAL WOMEN; WEIGHT-GAIN; INSULIN; RISK; DIAGNOSIS; SURVIVORS; OBESITY; MORTALITY AB Purpose To examine the association between serum C-peptide, a marker of insulin secretion, measured 3 years after a breast cancer diagnosis, and death resulting from all causes and breast cancer. Patients and Methods This was a prospective, observational study of 604 women enrolled onto the Health, Eating, Activity, and Lifestyle (HEAL) Study who were diagnosed with local or regional breast cancer between 1995 and 1998 and observed until death or December 31, 2006, whichever came first. The hazard ratio (HR) for all deaths and deaths owing to breast cancer and 95% CIs for the HR were estimated using multivariable stratified Cox regression analyses. Results Among women without type 2 diabetes, fasting C-peptide levels were associated with an increased risk of death resulting from all causes and from breast cancer. A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048). Associations between C-peptide levels and death as a result of breast cancer were stronger in certain subgroups, including women with type 2 diabetes, women with a body mass index less than 25 kg/m(2), women diagnosed with a higher stage of disease, and women whose tumors were estrogen receptor positive. Conclusion Treatment strategies to reduce C-peptide levels in patients with breast cancer, including dietary-induced weight loss, physical activity, and/or use of insulin-lowering medications, should be explored. C1 [Irwin, Melinda L.] Yale Sch Publ Hlth, New Haven, CT 06520 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Bethesda, MD 20892 USA. Univ Louisville, Louisville, KY 40292 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. RP Irwin, ML (reprint author), Yale Sch Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu RI Duggan, Catherine/F-9414-2015 OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010, T32-CA09661]; National Institutes of Health [M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX Supported by National Cancer Institute Grant Nos. N01-CN-75036-20, N01-CN-05228, and N01-PC-67010 and Training Grant No. T32-CA09661. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the National Institutes of Health, Grant No. M01-RR-00037 and the University of New Mexico Grant No. NCRR M01-RR-0997. Data collection for the Women's CARE Study at the University of Southern California was supported by Grant No. N01-HD-3-3175 from the National Institute of Child Health and Human Development, and patient identification was supported in part by Grant No. 050Q-8709-S1528 from the California Department of Health Services. NR 30 TC 69 Z9 70 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2011 VL 29 IS 1 BP 47 EP 53 DI 10.1200/JCO.2010.28.4752 PG 7 WC Oncology SC Oncology GA 700DB UT WOS:000285712400019 PM 21115859 ER PT J AU Goldstein, DS Holmes, C Sewell, L Pechnik, S Kopin, IJ AF Goldstein, David S. Holmes, Courtney Sewell, LaToya Pechnik, Sandra Kopin, Irwin J. TI Effects of Carbidopa and Entacapone on the Metabolic Fate of the Norepinephrine Prodrug L-DOPS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Dihydroxyphenylserine; norepinephrine; dihydroxyphenylglycol; dihydroxymandelic acid; orthostatic hypotension; autonomic failure; Parkinson's disease; DHPG; DOPS ID ORTHOSTATIC HYPOTENSION; DIHYDROXYPHENYLGLYCOL; REDUCTASE; DISEASES; FAILURE; ACID AB Background: L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect. Methods: Twelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured. Results: L-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 +/- 8 and 24 +/- 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 +/- 0.11 nmol/L) averaged less than 1/15 000th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS. Conclusions: After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation. C1 [Goldstein, David S.; Holmes, Courtney; Sewell, LaToya; Pechnik, Sandra; Kopin, Irwin J.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC 1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Division of Intramural Research of the National Institute of Neurological Disorders and Stroke, US National Institutes of Health, Bethesda, Maryland; Avance GmbH (Basel, Switzerland) FX The research reported here was supported by the Division of Intramural Research of the National Institute of Neurological Disorders and Stroke, US National Institutes of Health, Bethesda, Maryland. Avance GmbH (Basel, Switzerland) provided financial support for neurochemical assays. NR 19 TC 7 Z9 7 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2011 VL 51 IS 1 BP 66 EP 74 DI 10.1177/0091270010363476 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 694ZS UT WOS:000285341000008 PM 20220040 ER PT J AU Comer, JS Blanco, C Hasin, DS Liu, SM Grant, BF Turner, JB Olfson, M AF Comer, Jonathan S. Blanco, Carlos Hasin, Deborah S. Liu, Shang-Min Grant, Bridget F. Turner, J. Blake Olfson, Mark TI Health-Related Quality of Life Across the Anxiety Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID COMORBIDITY SURVEY REPLICATION; AVOIDANT PERSONALITY-DISORDER; DSM-IV DISORDERS; PANIC DISORDER; SOCIAL PHOBIA; UNITED-STATES; PRIMARY-CARE; MENTAL-DISORDERS; FUNCTIONAL IMPAIRMENT; PSYCHIATRIC-DISORDERS AB Objective: Although clinical studies have documented that specific anxiety disorders are associated with impaired psychosocial functioning, little is known regarding their comparative effects on health-related quality of life within a general population. The current analysis compares health-related quality of life in a US community-dwelling sample of adults with DSM-IV social anxiety disorder, generalized anxiety disorders (GAD), panic disorder, and specific phobia. Method: A face-to-face survey of a US nationally representative sample of over 43,000 adults aged 18 years and older residing in households and group quarters was conducted. Prevalence of DSM-IV anxiety disorders and relative associations with health-related quality of life indicators were examined. The survey was conducted from 2001 to 2002. Results: Roughly 9.8% of respondents met diagnostic criteria for at least 1 of 4 twelve-month DSM-IV anxiety disorders which, relative to the non-anxiety-disordered general population, were each associated with lower personal income, increased rates of 12-month physical conditions, and greater numbers of Axis I and Axis II DSM-IV psychiatric conditions. After adjusting for sociodemographic and clinical correlates, including other anxiety disorders, GAD was associated with significant decrements in the SF-12 mental component summary score. In similar models, GAD and, to a lesser extent, panic disorder were significantly associated with impairment in social functioning, role emotional, and mental health SF subscales. Conclusions: GAD, followed by panic disorder, appears to exact significant and independent tolls on health-related quality of life. Results underscore the importance of prompt and accurate clinical identification and improving access to effective interventions for these disorders. J Clin Psychiatry 2011;72(1)43-50 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY 10032 USA. [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Grant, Bridget F.] Natl Inst Alcohol Abuse & Alcohol Abuse & Alcohol, Bethesda, MD USA. RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr,Unit 24, New York, NY 10032 USA. EM mo49@columbia.edu RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU Eli Lilly; Bristol-Myers Squibb; Somaxon; Pfizer; GlaxoSmithKline; National Institutes of Health [AA000449, DA019606, DA020783, DA023200, MH076051, T32 MH016434, U18 HS016097, AA014223]; Mental Health Initiative (MINT) Foundation; American Foundation for Suicide Prevention; New York State Psychiatric Institute FX Dr Olfson has received grants from Eli Lilly and Bristol-Myers Squibb. Dr Blanco has received research support from Somaxon, Pfizer, and GlaxoSmithKline. Drs Cotner, Hasin, Grant, and Turner and Ms Liu report no competing interests.; This study is supported by National Institutes of Health grants AA000449 (Dr Grant, principal investigator, National Epidemiologic Survey on Alcohol and Related Conditions [NESARC]); DA019606, DA020783, DA023200, and MH076051 (Dr Blanco); T32 MH016434 (Dr Comer); U18 HS016097 (Dr Olfson); AA014223 (Dr Hasin); a grant from the Mental Health Initiative (MINT) Foundation (Dr Corner); a grant from the American Foundation for Suicide Prevention (Dr Blanco); and the New York State Psychiatric Institute (Drs Blanco, Olfson, and Hasin). NR 78 TC 52 Z9 54 U1 2 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2011 VL 72 IS 1 BP 43 EP 50 DI 10.4088/JCP.09m05094blu PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 719BT UT WOS:000287175100006 PM 20816036 ER PT J AU George, DT Phillips, MJ Lifshitz, M Lionetti, TA Spero, DE Ghassemzedeh, N Doty, L Umhau, JC Rawlings, RR AF George, David T. Phillips, Monte J. Lifshitz, Mariel Lionetti, Thomas A. Spero, David E. Ghassemzedeh, Niloofar Doty, Linda Umhau, John C. Rawlings, Robert R. TI Fluoxetine Treatment of Alcoholic Perpetrators of Domestic Violence: A 12-Week, Double-Blind, Randomized, Placebo-Controlled Intervention Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SELECT GROUP; AGGRESSION; ANGER; BEHAVIOR; MEN AB Objective: Behaviorally based therapies for the treatment of perpetrators who initiate intimate partner violence (IPV) have generally shown minimal therapeutic efficacy. To explore a new treatment approach for IPV, we examined the effects of a selective serotonin reuptake inhibitor on the irritability subscale score of the Modified Overt Aggression Scale. This score served as a surrogate marker for the anger and physical aggression that characterize perpetrators of IPV. Method: A 12-week, double-blind, randomized, placebo-controlled intervention study employing fluoxetine, alcohol treatment, and cognitive-behavioral therapy was performed. Sixty (46 men) non court-mandated, DSM-IV-diagnosed alcoholic perpetrators of IPV with a history of at least 2 episodes of IPV in the year prior to participation in the study were evaluated. The primary outcome measure was the score on the irritability subscale of the Modified Overt Aggression Scale. Secondary measures included anxiety, depression, and ratings by the perpetrator's spouse/significant other. The study was conducted from January 2002 through December 2007. Results: A repeated-measures analysis Of variance using the irritability subscale scores obtained from perpetrators who completed the 12-week study (n =24) showed a significant drug effect (F(1,21) = 12.09, P = .002). Last observation carried forward (F(1,32) = 4.24, P = .048) as well as intent-to-treat analysis (F(1,54) = 5.0, P = .034) also showed a significant drug effect. Spouses'/significant others' physical and nonphysical Partner Abuse Scale ratings showed a significant reduction of abuse over time (F(1,11) = 10.2, P = .009 and F(1,11) = 24.2, P = .0005, respectively). Conclusion: This is the first controlled study to show that a pharmacologic intervention employing a selective serotonin reuptake inhibitor, in conjunction with alcohol treatment and cognitive-behavioral therapy, can reduce measures of anger and physical aggression in alcoholic perpetrators of IPV. C1 [George, David T.] NIAAA, Lab Clin & Translat Studies, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. [Lionetti, Thomas A.; Spero, David E.] NIH, Clin Ctr Nursing, Bethesda, MD 20892 USA. RP George, DT (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, Clin Res Ctr, Bldg 10,Room 2-2352,10 Ctr Dr, Bethesda, MD 20892 USA. EM tedg@mail.nih.gov FU Intramural NIH HHS [ZIA AA000213-01] NR 34 TC 20 Z9 20 U1 2 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2011 VL 72 IS 1 BP 60 EP 65 DI 10.4088/JCP09m05256gry PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 719BT UT WOS:000287175100008 PM 20673556 ER PT J AU Brown, DL Anderson, CS Chervin, RD Kushida, CA Lewin, DS Malow, BA Redline, S Goldman, EB AF Brown, Devin L. Anderson, Craig S. Chervin, Ronald D. Kushida, Clete A. Lewin, Daniel S. Malow, Beth A. Redline, Susan Goldman, Edward B. TI Ethical Issues in the Conduct of Clinical Trials in Obstructive Sleep Apnea SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Obstructive sleep apnea; clinical trials; ethics ID POSITIVE AIRWAY PRESSURE; PROSPECTIVE PARALLEL TRIAL; BLOOD-PRESSURE; CPAP TREATMENT; PLACEBO; HYPOPNEA; QUALITY; METAANALYSIS; ADULTS; IMPACT AB Scientifically rigorous clinical trials are needed to test continuous positive airway pressure's (CPAP) effect on important clinical endpoints known to be associated with obstructive sleep apnea, such as myocardial infarction, cardiac arrhythmias, stroke, mortality, seizures, and cognitive function. In this "Special Article," we review the regulatory and ethical issues that surround the design and conduct of CPAP trials, including selection of the appropriate control condition, exclusion criteria, and follow-up duration. C1 [Brown, Devin L.] Univ Michigan, Ctr Cardiovasc, Stroke Program, Ann Arbor, MI 48109 USA. [Anderson, Craig S.] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia. [Anderson, Craig S.] Royal Prince Alfred Hosp, Sydney, NSW, Australia. [Chervin, Ronald D.] Univ Michigan, Sleep Disorders Ctr, Ann Arbor, MI 48109 USA. [Chervin, Ronald D.] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Kushida, Clete A.] Stanford Univ, Med Ctr, Stanford Sleep Disorders Clin, Stanford, CA 94305 USA. [Lewin, Daniel S.] NHLBI, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. [Malow, Beth A.] Vanderbilt Univ, Med Ctr, Dept Neurol, Sleep Disorders Div, Nashville, TN USA. [Redline, Susan] Harvard Univ, Sch Med, Dept Med, Div Sleep Med, Boston, MA USA. [Goldman, Edward B.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. RP Brown, DL (reprint author), Univ Michigan, Ctr Cardiovasc, Stroke Program, 1500 E Med Ctr Dr,SPC 5855, Ann Arbor, MI 48109 USA. EM devinb@umich.edu OI Brown, Devin/0000-0002-9815-3421 FU Respironics Foundation; Respironics, Inc; DyMedix Inc.; ResMed Inc. FX This was not an industry supported study. Dr. Brown has received materials support from Respironics, Inc and Puritan Bennett. Dr. Anderson has received financial support from the Respironics Foundation to undertake the Sleep Apnea Cardiovascular Endpoints (SAVE) trial. Dr. Kushida has received research support from Respironics, Inc, and ResMed. Dr. Chervin has served on the advisory board for Pavad Medical and as a consultant for Arena Pharmaceuticals. He is named as an inventor of intellectual property related to diagnosis and treatment of sleep disorders and owned by the University of Michigan. Dr. Redline has received research support from DyMedix Inc., use of equipment from Philips Respironics, and is the incumbent of an endowed professorship donated to Harvard Medical School by Dr. Peter Farrell, the founder and Board Chairman of ResMed Inc. The other authors have indicated no financial conflicts of interest. NR 37 TC 9 Z9 9 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2011 VL 7 IS 1 BP 103 EP 108 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 794SF UT WOS:000292920900015 PM 21344041 ER PT J AU Liu, Y Robbins, P Rosenberg, S Lee, C AF Liu, Y. Robbins, P. Rosenberg, S. Lee, C. TI NY-ESO-1 EXPRESSION IN MALIGNANT MELANOMA: A TARGET MARKER FOR IMMUNOTHERAPY SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Liu, Y.; Lee, C.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Robbins, P.; Rosenberg, S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 90 EP 91 PG 2 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300054 ER PT J AU Lee, CC Dennis, P Hornyak, T AF Lee, C-C. Dennis, P. Hornyak, T. TI CLINICAL AND HISTOLOGIC FEATURES OF FACIAL PAPULES IN COWDEN SYNDROME SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Meeting Abstract C1 [Lee, C-C.; Dennis, P.; Hornyak, T.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2011 VL 38 IS 1 BP 136 EP 136 PG 1 WC Dermatology; Pathology SC Dermatology; Pathology GA 682AI UT WOS:000284367300243 ER PT J AU Forcinito, P Andrade, AC Finkielstain, GP Baron, J Nilsson, O Lui, JC AF Forcinito, Patricia Andrade, Anenisia C. Finkielstain, Gabriela P. Baron, Jeffrey Nilsson, Ola Lui, Julian C. TI Growth-inhibiting conditions slow growth plate senescence SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CATCH-UP GROWTH; BONE-GROWTH; CHONDROCYTE DIFFERENTIATION; HORMONE-SECRETION; GENE-EXPRESSION; CELLULAR MEMORY; GROUP PROTEINS; RESTING ZONE; RECEPTOR; HYPOTHYROIDISM AB The mammalian growth plate undergoes programed senescence during juvenile life, causing skeletal growth to slow with age. We previously found that hypothyroidism in rats slowed both growth plate chondrocyte proliferation and growth plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of growth plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on growth plate senescence. We found that structural, functional, and molecular markers of growth plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of growth inhibition and hence that growth plate senescence is not simply a function of time per se but rather depends on growth. Journal of Endocrinology (2011) 208, 59-67 C1 [Forcinito, Patricia; Finkielstain, Gabriela P.; Baron, Jeffrey; Lui, Julian C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Bethesda, MD 20892 USA. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Ctr Mol Med, Dept Womens & Childrens Hlth, SE-17176 Stockholm, Sweden. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Inst, Pediat Endocrinol Unit, SE-17176 Stockholm, Sweden. [Andrade, Anenisia C.; Nilsson, Ola] Karolinska Univ Hosp, SE-17176 Stockholm, Sweden. RP Lui, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dev Endocrinol Branch, Program Dev Endocrinol & Genet, NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM luichunk@mail.nih.gov RI Lui, Chun Kin Julian/E-2253-2012; OI Nilsson, Ola/0000-0002-9986-8138 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; Swedish Research Council [K2007-52X-20316-01-4]; Swedish Society of Medicine; HKH kronprinsessan Lovisas Forening for Barnasjukvard; Sallskapet Barnavard; Stiftelsen Frimurare Barnhuset i Stockholm FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. ON was supported by grants from the Swedish Research Council (K2007-52X-20316-01-4), the Swedish Society of Medicine, HKH kronprinsessan Lovisas Forening for Barnasjukvard, Sallskapet Barnavard, and Stiftelsen Frimurare Barnhuset i Stockholm. NR 32 TC 11 Z9 11 U1 0 U2 7 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JAN PY 2011 VL 208 IS 1 BP 59 EP 67 DI 10.1677/JOE-10-0302 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 690JL UT WOS:000285000000008 PM 20974641 ER PT J AU Yan, H Wang, YH Cheng, WH Sun, LG AF Yan, Hong Wang, Yuhong Cheng, Wenhan Sun, Liguang TI Millennial mercury records derived from ornithogenic sediment on Dongdao Island, South China Sea SO JOURNAL OF ENVIRONMENTAL SCIENCES LA English DT Article DE South China Sea; red-footed booby; ornithogenic sediment; mercury; anthropogenic source ID ATMOSPHERIC MERCURY; GEOCHEMICAL EVIDENCE; PENGUIN POPULATIONS; LAKE-SEDIMENTS; TRACE-METALS; PEAT BOG; DEPOSITION; EMISSIONS; SILVER; ACCUMULATION AB Two ornithogenic sediment cores, which have a time span of 1000 years and are influenced by red-footed booby (Sula sula), were collected from Dongdao Islands, South China Sea. The determined mercury concentrations of the two cores show similar and substantial fluctuations during the past millennium, and the fluctuations are most likely caused by the changes in mercury level of the ocean environment and in anthropogenic Hg emission. For the past 500 years, the mercury concentration in the red-footed booby excrement has a striking association with global anthropogenic mercury emission. The mercury concentration increased rapidly after AD 1600 in corresponding to beginning of the unparalleled gold and silver mining in South Central America that left a large volume of anthropogenic mercury pollution. Since the Industrial Revolution, the mercury level has increased at a fast pace, very likely caused by modern coal combustion, chlor-alkali and oil refining industries. The comparison of mercury profiles from different places on earth suggested that anthropogenic mercury pollution after the Industrial Revolution is more severe in Northern Hemisphere than in Antarctica. C1 [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. [Yan, Hong; Cheng, Wenhan; Sun, Liguang] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China. RP Wang, YH (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM yanhong19860124@hotmail.com; yuhong_wang@yahoo.com; slg@ustc.edu.cn RI Yan, Hong/I-8970-2014 FU Natural Science Foundation of China (NSFC) [40730107]; National Basic Research Program (973) of China [2010CB428902] FX This work was supported by the Natural Science Foundation of China (NSFC) (No. 40730107) and the National Basic Research Program (973) of China (No. 2010CB428902). The authors would like to thank Nan Jia, Sanping Zhao, Xuebin Yin and Honghao Luo for their help in sampling and analyzing. NR 38 TC 2 Z9 3 U1 5 U2 35 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-0742 EI 1878-7320 J9 J ENVIRON SCI-CHINA JI J. Environ. Sci. PY 2011 VL 23 IS 9 BP 1415 EP 1423 DI 10.1016/S1001-0742(10)60603-1 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 825XL UT WOS:000295315300002 PM 22432275 ER PT J AU Lemen, RA Anderson, H Bailar, JC Bingham, E Castleman, B Frank, AL Huff, J Ladou, J Melius, J Monforton, C Robbins, A Teitelbaum, DT Welch, LS AF Lemen, Richard A. Anderson, Henry Bailar, John C. Bingham, Eula Castleman, Barry Frank, Arthur L. Huff, James Ladou, Joseph Melius, James Monforton, Celeste Robbins, Anthony Teitelbaum, Daniel Thau Welch, Laura S. TI Exposure science will not increase protection of workers from asbestos-caused diseases: NIOSH fails to provide needed public health action and leadership SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Letter ID CHRYSOTILE ASBESTOS; GLOBAL BAN C1 [Lemen, Richard A.] US PHS, Canton, GA USA. [Lemen, Richard A.] NIOSH, Canton, GA USA. [Anderson, Henry] Wisconsin Div Publ Hlth, Madison, WI USA. [Bailar, John C.] Univ Chicago, Chicago, IL 60637 USA. [Bailar, John C.] Natl Acad, Chicago, IL USA. [Bingham, Eula] Univ Cincinnati, Cincinnati, OH USA. [Frank, Arthur L.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. [Huff, James] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Ladou, Joseph] Univ Calif San Francisco, Div Occupat & Environm Med, San Francisco, CA 94143 USA. [Melius, James] NYS Laborers Hlth & Safety Fund, Albany, NY USA. [Monforton, Celeste] Amer Publ Hlth Assoc, Occupat Hlth & Safety Sect, Washington, DC USA. [Robbins, Anthony] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Teitelbaum, Daniel Thau] Colorado Sch Publ Hlth, Denver, CO USA. [Welch, Laura S.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. EM rlemen421@yahoo.com NR 14 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD JAN-FEB PY 2011 VL 21 IS 1 BP 114 EP 115 DI 10.1038/jes.2010.53 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 696PF UT WOS:000285452900013 PM 21170057 ER PT J AU Karani, R Chheda, SG Dunn, K Locke, K Bates, CK AF Karani, Reena Chheda, Shobhina G. Dunn, Kathel Locke, Kenneth Bates, Carol K. TI Update in Medical Education SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE advances; innovations; general internal medicine; manuscripts; education ID CLINICAL SKILLS; PROFESSIONALISM; SIMULATION C1 [Karani, Reena] Mt Sinai Sch Med, Dept Med Educ, Samuel M Bronfman Dept Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Chheda, Shobhina G.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Gen Internal Med Sect, Madison, WI USA. [Dunn, Kathel] Natl Lib Med, Bethesda, MD USA. [Locke, Kenneth] Univ Toronto, Dept Med, Div Gen Med, Toronto, ON, Canada. [Bates, Carol K.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Karani, R (reprint author), Mt Sinai Sch Med, Dept Med Educ, Samuel M Bronfman Dept Med, Brookdale Dept Geriatr & Palliat Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM reena.karani@mssm.edu OI Dunn, Kathel/0000-0002-6967-130X NR 12 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2011 VL 26 IS 1 BP 83 EP 87 DI 10.1007/s11606-010-1502-y PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 708CJ UT WOS:000286338900022 PM 20853065 ER PT J AU Ruffin, J AF Ruffin, John TI Health Literacy and the Elimination of Health Disparities Foreword SO JOURNAL OF HEALTH COMMUNICATION LA English DT Editorial Material C1 Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA. RP Ruffin, J (reprint author), Natl Inst Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2011 VL 16 SU 3 SI SI BP 1 EP 2 DI 10.1080/10810730.2011.604708 PG 2 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 887TI UT WOS:000299952500001 PM 21951236 ER PT J AU Hesse, BW O'Connell, M Augustson, EM Chou, WYS Shaikh, AR Rutten, LJF AF Hesse, Bradford W. O'Connell, Mary Augustson, Erik M. Chou, Wen-Ying Sylvia Shaikh, Abdul R. Rutten, Lila J. Finney TI Realizing the Promise of Web 2.0: Engaging Community Intelligence SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION; SCIENTIFIC COLLABORATION; INTERNET; SCIENCE; QUALITY; PARTICIPATION; PATIENT; SEARCH; IMPACT AB Discussions of Health 2.0, a term first coined in 2005, were guided by three main tenets: (a) health was to involve more participation, because an evolution in the web encouraged more direct consumer engagement in their own health care; (b) data was to become the new "Intel Inside" for systems supporting the vital decisions in health; and (c) a sense of collective intelligence from the network would supplement traditional sources of knowledge in health decision making. Interests in understanding the implications of a new paradigm for patient engagement in health and health care were kindled by findings from surveys such as the National Cancer Institute's Health Information National Trends Survey, showing that patients were quick to look online for information to help them cope with disease. This article considers how these 3 facets of Health 2.0-participation, data, and collective intelligence-can be harnessed to improve the health of the nation according to Healthy People 2020 goals. The authors begin with an examination of evidence from behavioral science to understand how Web 2.0 participative technologies may influence patient processes and outcomes, for better or worse, in an era of changing communication technologies. The article then focuses specifically on the clinical implications of Health 2.0 and offers recommendations to ensure that changes in the communication environment do not detract from national (e. g., Healthy People 2020) health goals. Changes in the clinical environment, as catalyzed by the Health Information Technology for Economic and Clinical Health Act to take advantage of Health 2.0 principles in evidence-based ways, are also considered. C1 [Hesse, Bradford W.; O'Connell, Mary; Augustson, Erik M.; Chou, Wen-Ying Sylvia; Shaikh, Abdul R.] NCI, NIH, Bethesda, MD 20892 USA. [Rutten, Lila J. Finney] SAIC Frederick Inc, Clin Monitoring Res Program, NCI Frederick, Frederick, MD USA. RP Hesse, BW (reprint author), NCI, NIH, 6130 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA. EM hesseb@mail.nih.gov OI Hesse, Bradford/0000-0003-1142-1161 FU CCR NIH HHS [HHSN261200800001C]; NCI NIH HHS [HHSN261200800001E, HHSN261200800001E] NR 77 TC 27 Z9 29 U1 5 U2 27 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1081-0730 EI 1087-0415 J9 J HEALTH COMMUN JI J. Health Commun. PY 2011 VL 16 SU 1 BP 10 EP 31 DI 10.1080/10810730.2011.589882 PG 22 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 887SQ UT WOS:000299950500003 PM 21843093 ER PT J AU Johnson, SE Baur, C Meissner, HI AF Johnson, Sarah E. Baur, Cynthia Meissner, Helen I. TI Back to Basics: Why Basic Research Is Needed to Create Effective Health Literacy Interventions SO JOURNAL OF HEALTH COMMUNICATION LA English DT Editorial Material AB Limited health literacy is increasingly recognized as a public health problem. Growing recognition of the problem-and the need for solutions-creates an imperative for the field of health literacy research to identify effective interventions. The National Action Plan to Improve Health Literacy (U. S. DHHS, 2010) recommends increased basic research in health literacy. This paper elaborates on this call by explicating what is meant by basic research and describing several of the ways in which basic research will benefit the field of health literacy research and, particularly, progress toward designing successful interventions. C1 [Johnson, Sarah E.; Meissner, Helen I.] NIH, US Dept HHS, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Baur, Cynthia] Ctr Dis Control & Prevent, US Dept HHS, Off Associate Director Commun, Atlanta, GA USA. RP Meissner, HI (reprint author), NIH, US Dept HHS, Off Behav & Social Sci Res, 31 Ctr Dr,Bldg 31,Room B1C19, Bethesda, MD 20892 USA. EM meissneh@od.nih.gov NR 25 TC 5 Z9 5 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2011 VL 16 SU 3 SI SI BP 22 EP 29 DI 10.1080/10810730.2011.604707 PG 8 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 887TI UT WOS:000299952500006 PM 21951241 ER PT J AU Thompson, OM Yaroch, AL Moser, RP Rutten, LJF Petrelli, JM Smith-Warner, SA Masse, LC Nebeling, L AF Thompson, Olivia M. Yaroch, Amy L. Moser, Richard P. Rutten, Lila J. Finney Petrelli, Jennifer M. Smith-Warner, Stephanie A. Masse, Louise C. Nebeling, Linda TI Knowledge of and Adherence to Fruit and Vegetable Recommendations and Intakes: Results of the 2003 Health Information National Trends Survey SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID CANCER CONTROL; DIETARY CHANGE; CONSUMPTION; PREVENTION; BEHAVIOR; COMMUNICATION; ASSOCIATION; NONRESPONSE; NUTRITION; AWARENESS AB Attention to cancer-relevant communication (e. g., fruit/vegetable intake recommendations) through various media has been shown to be a pivotal step in reduction of the cancer burden, thus underscoring the importance of examining associations between exposure to health media and knowledge of and adherence to fruit/vegetable intake recommendations. The purpose of the present study was to assess factors associated with fruit/vegetable intake knowledge and behavior. The authors analyzed data collected from the 2003 Health Information National Trends Survey to evaluate the effect of fruit/vegetable intake knowledge on behavior, and the relationship of this effect with biobehavioral, sociodemographic, and communication characteristics. Participants who were knowledgeable of fruit/vegetable intake recommendations and consumed at least 5 fruit/vegetable servings per day were classified as informed compliers. Associations were observed for being an informed complier and paying "a lot" of attention to health media on the radio, in the newspaper, and in magazines and "a little" or "some" attention to health media in magazines or on the Internet. The recent explosion of available cancer-related information through various media underscores the importance of examining associations between exposure to health media and knowledge of and adherence to fruit/vegetable intake recommendations. C1 [Thompson, Olivia M.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot Social & Behav Hlth, Omaha, NE 68198 USA. [Yaroch, Amy L.] Ctr Human Nutr, Omaha, NE USA. [Moser, Richard P.; Nebeling, Linda] NCI, Bethesda, MD 20892 USA. [Rutten, Lila J. Finney] NCI, Clin Monitoring Res Program, Hlth Commun & Informat Res Branch, SAIC Frederick Inc, Frederick, MD 21701 USA. [Smith-Warner, Stephanie A.] Harvard Univ, Boston, MA 02115 USA. [Masse, Louise C.] Ctr Community Child Hlth Res, Vancouver, BC, Canada. RP Thompson, OM (reprint author), Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot Social & Behav Hlth, Omaha, NE 68198 USA. EM othompson@unmc.edu NR 33 TC 9 Z9 9 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PY 2011 VL 16 IS 3 BP 328 EP 340 DI 10.1080/10810730.2010.532293 PG 13 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 730WD UT WOS:000288065600008 PM 21161813 ER PT J AU Sutherland, IW Mori, A Montgomery, J Fleming, KL Anderson, JM Valenzuela, JG Severson, DW Black, WC AF Sutherland, Ian W. Mori, Akio Montgomery, John Fleming, Karen L. Anderson, Jennifer M. Valenzuela, Jesus G. Severson, David W. Black, William C. TI A Linkage Map of the Asian Tiger Mosquito (Aedes albopictus) Based on cDNA Markers SO JOURNAL OF HEREDITY LA English DT Article DE Aedes albopictus; cDNA markers; linkage map; SSCP analysis ID EQUINE ENCEPHALITIS-VIRUS; ST-LOUIS ENCEPHALITIS; INTERSPECIFIC VARIATION; VECTOR COMPETENCE; COLD-HARDINESS; SSCP ANALYSIS; DENGUE VIRUS; POTOSI VIRUS; PINE-BLUFF; AEGYPTI AB The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), is an important vector of a number of arboviruses, and populations exhibit extreme variation in adaptive traits such as egg diapause, cold hardiness, and autogeny (ability to mature a batch of eggs without blood feeding). The genetic basis of some of these traits has been established, but lack of a high-resolution linkage map has prevented in-depth genetic analyses of the genes underlying these complex traits. We report here on the breeding of 4 F(1) intercross mapping families and the use of these to locate 35 cDNA markers to the A. albopictus linkage map. The present study increases the number of markers on the A. albopictus cDNA linkage map from 38 to 73 and the density of markers from 1 marker/5.7 cM to 1 marker/2.9 cM and adds 9, 16, and 10 markers to the 3 linkage groups, respectively. The overall lengths of the 3 linkage groups are 64.5, 76.5, and 71.6 cM, respectively, for a combined length of 212.6 cM. Despite conservation in the order of most genes among the 4 families and a previous mapping family, we found substantial heterogeneity in the amount of recombination among markers. This was most marked in linkage group I, which varied between 16.7 and 69.3 cM. A map integrating the results from these 4 families with an earlier cDNA linkage map is presented. C1 [Sutherland, Ian W.; Montgomery, John; Fleming, Karen L.; Black, William C.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. [Mori, Akio; Severson, David W.] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA. [Anderson, Jennifer M.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Black, WC (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. EM wcb4@lamar.colostate.edu FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [N01-AI 25489, AI059342]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX National Institute of Allergy and Infectious Diseases, National Institutes of Health (contract N01-AI 25489 to C. S. U., AI059342); Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 54 TC 2 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JAN-FEB PY 2011 VL 102 IS 1 BP 102 EP 112 DI 10.1093/jhered/esq105 PG 11 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 696CM UT WOS:000285419500012 PM 21148282 ER PT J AU Pearson, JCL Weinstock, D AF Pearson, Joy C. Lee Weinstock, Deborah TI Minimizing Safety and Health Impacts at Disaster Sites: the Need for Comprehensive Worker Safety and Health Training Based on an Analysis of National Disasters in the US SO JOURNAL OF HOMELAND SECURITY AND EMERGENCY MANAGEMENT LA English DT Article DE worker safety and health; disaster site workers; worker training ID RECOVERY; CLEANUP; RESCUE AB Skilled support personnel responding to national disasters are at great risk to develop physical and mental health problems that can cause short- and long-term disability and prove to be fatal. Health issues endured by these workers can be attributed to a lack of pre-deployment training. Costs accrued for health care from hazardous exposures in disaster zones continues to increase as symptoms manifest years after the event. Illnesses could be prevented if workers received comprehensive training prior to deployment at the site. Pre-deployment occupational safety and health training is critical to protect the well-being of disaster site workers. C1 [Pearson, Joy C. Lee; Weinstock, Deborah] NIEHS Natl Clearinghouse Worker Safety & Hlth Tra, Res Triangle Pk, NC 27709 USA. RP Pearson, JCL (reprint author), NIEHS Natl Clearinghouse Worker Safety & Hlth Tra, Res Triangle Pk, NC 27709 USA. RI Hamzah, Musili/B-2429-2012 NR 27 TC 0 Z9 0 U1 1 U2 7 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1547-7355 J9 J HOMEL SECUR EMERG JI J. Homel. Secur. Emerg. Manag. PY 2011 VL 8 IS 1 AR 46 DI 10.2202/1547-7355.1757 PG 18 WC Public Administration SC Public Administration GA 814PN UT WOS:000294469300002 ER PT J AU Fedyna, A Drayna, D Kang, C AF Fedyna, Alison Drayna, Dennis Kang, Changsoo TI Characterization of a mutation commonly associated with persistent stuttering: evidence for a founder mutation SO JOURNAL OF HUMAN GENETICS LA English DT Article DE founder; GNPTAB; haplotype; lysosome; mucolipidosis; stuttering ID HAPLOTYPE RECONSTRUCTION; LINKAGE AB Stuttering is a disorder that affects the fluency of speech. It has been shown to have high heritability and has recently been linked to mutations in the GNPTAB gene. One such mutation, Glu1200Lys, has been repeatedly observed in unrelated families and individual cases. Eight unrelated individuals carrying this mutation were analyzed in an effort to distinguish whether these arise from repeated mutation at the same site, or whether they represent a founder mutation with a single origin. Results show that all 12 chromosomes carrying this mutation share a common haplotype in this region, indicating that it is a founder mutation. Further analysis estimated the age of this allele to be similar to 572 generations. Construction of a cladogram tracing the mutation through our study sample also supports the founder mutation hypothesis. Journal of Human Genetics (2011) 56, 80-82; doi:10.1038/jhg.2010.125; published online 14 October 2010 C1 [Fedyna, Alison; Drayna, Dennis; Kang, Changsoo] Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 20850 USA. RP Kang, C (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. EM kangch@nidcd.nih.gov FU NIDCD/National Institutes of Health [Z01-000046-10] FX We thank M Hashim Raza for helpful discussion and T Friedman and K Noben-Trauth for valuable comments on the manuscript. This work was supported by NIDCD/National Institutes of Health intramural research grant Z01-000046-10. NR 12 TC 5 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD JAN PY 2011 VL 56 IS 1 BP 80 EP 82 DI 10.1038/jhg.2010.125 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 711IX UT WOS:000286585200017 PM 20944643 ER PT J AU Yeboah, J Crouse, JR Bluemke, DA Lima, JAC Polak, JF Burke, GL Herrington, DM AF Yeboah, J. Crouse, J. R. Bluemke, D. A. Lima, J. A. C. Polak, J. F. Burke, G. L. Herrington, D. M. TI Endothelial dysfunction is associated with left ventricular mass (assessed using MRI) in an adult population (MESA) SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE left ventricular mass; endothelial function; brachial flow-mediated dilation; population ID HYPERTENSIVE PATIENTS; NITRIC-OXIDE; PROGNOSTIC IMPLICATIONS; DEPENDENT VASODILATION; ELDERLY COHORT; HYPERTROPHY; RISK; ATHEROSCLEROSIS; DILATATION; GEOMETRY AB Brachial flow-mediated dilation (FMD) is a measure of endothelial nitric oxide bioavailability. Endothelial nitric oxide controls vascular tone and is likely to modify the ventricular muscle coupling mechanism. The association between left ventricular mass and FMD is not well understood. We assessed the association between left ventricular mass index (LVMI) and FMD in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a population-based study of 6814 adults free of clinical cardiovascular disease at baseline who were recruited from six US clinics. LVMI (left ventricular mass per body surface area) and FMD were measured in 2447 subjects. Linear regression analysis was used to evaluate the association. The subjects had a mean age of 61.2 +/- 9.9 years, 51.2% females with 34.3% Caucasians, 21.6% Chinese, 19.4% African Americans and 24.7% Hispanics. The mean body mass index (BMI) was 27.4 +/- 4.8 kgm(-2), 9.4% had diabetes, 11% were current smokers and 38% hypertensives. The mean +/- s.d. LVMI was 78.1 +/- 15.9 gm(-2) and mean +/- s.d. FMD was 4.4% +/- 2.8%. In univariate analysis, LVMI was inversely correlated with FMD (r=-0.20, P < 0.0001). In the multivariable analysis, LVMI was associated with FMD (beta coefficient (se)=-0.50 (0.11), P < 0.001 (0.5 gm(-2) reduction in LVMI per 1% increase in FMD)) after adjusting for age, gender, race/ethnicity, systolic blood pressure, diabetes mellitus, smoking, weight, statin use, antihypertensive medication use, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. The association between brachial flow mediated dilation and LVMI maybe independent of traditional CV risk factors in population based adults. Journal of Human Hypertension (2011) 25, 25-31; doi:10.1038/jhh.2010.25; published online 18 March 2010 C1 [Yeboah, J.] Univ Virginia, Sch Med, Dept Cardiol, Charlottesville, VA 22908 USA. [Crouse, J. R.; Herrington, D. M.] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Bluemke, D. A.] NIH, Bethesda, MD 20892 USA. [Lima, J. A. C.] Johns Hopkins Sch Med, Dept Internal Med Cardiol Publ Hlth, Baltimore, MD USA. [Polak, J. F.] Tuft New England Med Ctr, Dept Radiol, Boston, MA USA. [Burke, G. L.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Yeboah, J (reprint author), Univ Virginia, Med Ctr, Dept Internal Med Cardiol, Charlottesville, VA 22908 USA. EM jy5y@virginia.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung and Blood Institute, Bethesda, MD, USA [N01-HC-95159, N01-HC-95166, N01-HC-95169, NHLBI T32 HL076132] FX This research was supported by contracts N01-HC-95159 through N01-HC-95166 and N01-HC-95169, and grants NHLBI T32 HL076132, all from the National Heart, Lung and Blood Institute, Bethesda, MD, USA. NR 31 TC 18 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD JAN PY 2011 VL 25 IS 1 BP 25 EP 31 DI 10.1038/jhh.2010.25 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 692ED UT WOS:000285133800005 PM 20237502 ER PT J AU Ho, JE Levy, D Rose, L Johnson, AD Ridker, PM Chasman, DI AF Ho, Jennifer E. Levy, Daniel Rose, Lynda Johnson, Andrew D. Ridker, Paul M. Chasman, Daniel I. TI Discovery and replication of novel blood pressure genetic loci in the Women's Genome Health Study SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; genetics; hypertension; women ID C-REACTIVE PROTEIN; WIDE ASSOCIATION; HYPERTENSION SUSCEPTIBILITY; PROSPECTIVE COHORT; RISK; POLYMORPHISMS; METAANALYSIS; PROGRESSION; POPULATION; EXPRESSION AB Objectives Genome-wide association meta-analyses have recently identified multiple loci associated with blood pressure. We sought to validate previously identified blood pressure loci by replication in a single large homogeneous population-based cohort and to identify new genome-wide significant loci using both conventional and expression-guided approaches. Methods We examined the associations of 18 singlenucleotide polymorphisms ( SNPs) with genome-wide significance ( P < 5.0 X 10(-8), 'primary'), and 13 suggestive SNPs ( 5.0 x 10(-8) < P< 5.6 x 10(-5), 'secondary'), all from previously established genome-wide association studies, with self-reported blood pressure in 23 019 women from the Women's Genome Health Study. We then targeted for replication 12 gene expression-associated SNPs (eSNPs) that were also previously associated with blood pressure phenotypes. Results Using these replication strategies, we found confirmatory evidence for 13/18 primary SNPs, 3/13 secondary SNPs, and 4/12 eSNPs in the Women's Genome Health Study. Meta-analysis combining the Women's Genome Health Study results with prior study results revealed one previously unrecognized blood pressure locus with genome-wide significance: a BLK-GATA4-adjacent region (P=3.2 x 10(-8)). Conclusion In this analysis, conventional and eSNP-guided strategies were complementary and illustrate two ways for extending initial genome-wide association results for discovery of new genes involved in human disease. Using this strategy, we report a newly identified blood pressure locus, BLK-GATA4, that may further understanding of the complex genetic pathways regulating blood pressure. J Hypertens 29:62-69 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Ho, Jennifer E.; Levy, Daniel; Johnson, Andrew D.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Levy, Daniel; Johnson, Andrew D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02215 USA. [Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA USA. RP Chasman, DI (reprint author), Brigham & Womens Hosp, Div Prevent Med, Ctr Cardiovasc Dis Prevent, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM dchasman@rics.bwh.harvard.edu RI Johnson, Andrew/G-6520-2013; OI Ho, Jennifer/0000-0002-7987-4768 FU National Heart, Lung, and Blood Institute [HL-043851, HL-69757]; National Cancer Institute [CA-047988]; Donald W. Reynolds Foundation; Fondation Leducq; Amgen; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195] FX The WGHS is supported by HL-043851 and HL-69757 from the National Heart, Lung, and Blood Institute and CA-047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (J.E.H., D.L, contract No. N01-HC-25195). NR 35 TC 33 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2011 VL 29 IS 1 BP 62 EP 69 DI 10.1097/HJH.0b013e3283406927 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 695MW UT WOS:000285375800012 PM 21045733 ER PT J AU Chacon-Salinas, R Limon-Flores, AY Chavez-Blanco, AD Gonzalez-Estrada, A Ullrich, SE AF Chacon-Salinas, Rommel Limon-Flores, Alberto Y. Chavez-Blanco, Alma D. Gonzalez-Estrada, Alexei Ullrich, Stephen E. TI Mast Cell-Derived IL-10 Suppresses Germinal Center Formation by Affecting T Follicular Helper Cell Function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CXC CHEMOKINE RECEPTOR-5; HUMORAL IMMUNE-RESPONSES; ULTRAVIOLET-RADIATION; SYSTEMIC SUPPRESSION; SKIN-CANCER; IRRADIATION; DIFFERENTIATION; MICE; HYPERSENSITIVITY; INTERLEUKIN-21 AB The most prevalent cancer diagnosed in the world is sunlight-induced skin cancer. In addition to being a complete carcinogen, UV radiation, the causative agent of skin cancer, induces immune suppression. Because UV-induced immune suppression is a well-recognized risk factor for skin cancer induction, it is crucial to understand the mechanisms underlying UV-induced immune suppression. Mast cells, which have recently emerged as immune regulatory cells, are particularly important in UV-induced immune suppression. UV exposure does not induce immune suppression in mast cell-deficient mice. We report that UV irradiation blocks germinal center (GC) formation, Ab secretion, and T follicular helper (Tfh) cell function, in part by altering the expression of transcription factors BCL-6 and BLIMP-1. No suppression of GC formation, Tfh cell IL-21 expression, or Ab secretion was observed in UV-irradiated mast cell-deficient (Kit(W-sh/W-sh)) mice. When mast cell-deficient mice were reconstituted with wild type mast cells, immune suppression was restored. Reconstituting the mast cell-deficient mice with bone marrow-derived mast cells from IL-10-deficient mice failed to restore the ability of UV radiation to suppress GC formation. Our findings demonstrate a function for mast cells, suppression of Tfh cell production, GC formation, and Ab production in vivo. The Journal of Immunology, 2011, 186: 25-31. C1 [Ullrich, Stephen E.] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Unit 902, Houston, TX 77030 USA. [Chacon-Salinas, Rommel; Limon-Flores, Alberto Y.] Univ Texas MD Anderson Canc Ctr, Ctr Canc Immunol Res, Houston, TX 77030 USA. [Chavez-Blanco, Alma D.] NCI, Dept Basic Res, Bethesda, MD 20892 USA. [Gonzalez-Estrada, Alexei] Anahuac Univ, Hlth Sci Ctr, Mexico City, DF, Mexico. [Ullrich, Stephen E.] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA. RP Ullrich, SE (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Immunol, Unit 902, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM sullrich@mdanderson.org OI Limon-Flores, Alberto Yairh/0000-0003-4718-4356; Gonzalez-Estrada, Alexei/0000-0002-5754-6130 FU National Cancer Institute [CA131207, CA112660, CA16672] FX This work was supported by National Cancer Institute Grants CA131207 and CA112660. The animal, histology, and flow cytometry facilities at the MD Anderson Cancer Center are supported in part by National Cancer Institute Core Grant CA16672. NR 42 TC 44 Z9 45 U1 3 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 25 EP 31 DI 10.4049/jimmunol.1001657 PG 7 WC Immunology SC Immunology GA 699UP UT WOS:000285688700009 PM 21098222 ER PT J AU Li, M Gustchina, A Glesner, J Wunschmann, S Vailes, LD Chapman, MD Pomes, A Wlodawer, A AF Li, Mi Gustchina, Alla Glesner, Jill Wuenschmann, Sabina Vailes, Lisa D. Chapman, Martin D. Pomes, Anna Wlodawer, Alexander TI Carbohydrates Contribute to the Interactions between Cockroach Allergen Bla g 2 and a Monoclonal Antibody SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; IGE; EPITOPES; RECOGNITION; EXPOSURE; BINDING; PROTEIN; BLA-G-2; ASTHMA; DETERMINANTS AB The crystal structure of a murine mAb, 4C3, that binds to the C-terminal lobe of the cockroach allergen Bla g 2 has been solved at 1.8 angstrom resolution. Binding of 4C3 involves different types of molecular interactions with its epitope compared with those with the mAb 7C11, which binds to the N-terminal lobe of Bla g 2. We found that the 4C3 surface epitope on Bla g 2 includes a carbohydrate moiety attached to Asn(268) and that a large number of Ag-Ab contacts are mediated by water molecules and ions, most likely zinc. Ab binding experiments conducted with an enzymatically deglycosylated Bla g 2 and a N268Q mutant showed that the carbohydrate contributes, without being essential, to the Bla g 2-4C3 mAb interaction. Inhibition of IgE Ab binding by the mAb 4C3 shows a correlation of the structurally defined epitope with reactivity with human IgE. Site-directed mutagenesis of the 4C3 mAb epitope confirmed that the amino acids Lys(251), Glu(233), and Ile(199) are important for the recognition of Bla g 2 by the 4C3 mAb. The results show the relevance of x-ray crystallographic studies of allergen-Ab complexes to identify conformational epitopes that define the antigenic surface of Bla g 2. The Journal of Immunology, 2011, 186: 333-340. C1 [Gustchina, Alla] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. [Glesner, Jill; Wuenschmann, Sabina; Vailes, Lisa D.; Chapman, Martin D.; Pomes, Anna] INDOOR Biotechnol Inc, Charlottesville, VA 22903 USA. RP Gustchina, A (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Bldg 539, Frederick, MD 21702 USA. EM gustchia@mail.nih.gov OI Pomes, Anna/0000-0002-8729-1829 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases [R01AI077653]; Office of Science, Office of Basic Energy Sciences, U. S. Department of Energy [W-31-109-ENG-38] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and in part by federal funds from the National Cancer Institute, National Institutes of Health under Contract HHSN261200800001E. A. P. and M. D. C. were supported in part by Grant R01AI077653 from the National Institute of Allergy and Infectious Diseases. We used beamline 22-ID of the Southeast Regional Collaborative Access Team, located at the Advanced Photon Source, Argonne National Laboratory. Use of the Advanced Photon Source was supported by the Office of Science, Office of Basic Energy Sciences, U. S. Department of Energy under Contract W-31-109-ENG-38. NR 41 TC 17 Z9 17 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 333 EP 340 DI 10.4049/jimmunol.1002318 PG 8 WC Immunology SC Immunology GA 699UP UT WOS:000285688700040 PM 21123808 ER PT J AU van Bockel, DJ Price, DA Munier, ML Venturi, V Asher, TE Ladell, K Greenaway, HY Zaunders, J Douek, DC Cooper, DA Davenport, MP Kelleher, AD AF van Bockel, David J. Price, David A. Munier, Mee Ling Venturi, Vanessa Asher, Tedi E. Ladell, Kristin Greenaway, Hui Yee Zaunders, John Douek, Daniel C. Cooper, David A. Davenport, Miles P. Kelleher, Anthony D. TI Persistent Survival of Prevalent Clonotypes within an Immunodominant HIV Gag-Specific CD8(+) T Cell Response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE SIV INFECTION; LYMPHOCYTE ESCAPE; HUMAN CYTOMEGALOVIRUS; CTL ESCAPE; RECEPTOR REPERTOIRE; CD8-T-CELL MEMORY; PERIPHERAL-BLOOD; CD4-T-CELL HELP; AIDS PATIENTS; CMV DISEASE AB CD8(+) T cells play a significant role in the control of HIV replication, yet the associated qualitative and quantitative factors that determine the outcome of infection remain obscure. In this study, we examined Ag-specific CD8(+) TCR repertoires longitudinally in a cohort of HLA-B*2705(+) long-term nonprogressors with chronic HIV-1 infection using a combination of molecular clonotype analysis and polychromatic flow cytometry. In each case, CD8(+) T cell populations specific for the immunodominant p24 Gag epitope KRWIILGLNK (KK10; residues 263-272) and naturally occurring variants thereof, restricted by HLA-B*2705, were studied at multiple time points; in addition, comparative data were collected for CD8(+) T cell populations specific for the CMV pp65 epitope NLVPMVATV (NV9; residues 495-503), restricted by HLA-A*0201. Dominant KK10-specific clonotypes persisted for several years and exhibited greater stability than their contemporaneous NV9-specific counterparts. Furthermore, these dominant KK10-specific clonotypes exhibited cross-reactivity with antigenic variants and expressed significantly higher levels of CD127 (IL-7R alpha) and Bcl-2. Of note, we also found evidence that promiscuous TCR alpha-chain pairing associated with alterations in fine specificity for KK10 variants could contribute to TCR beta-chain prevalence. Taken together, these data suggest that an antiapoptotic phenotype and the ability to cross-recognize variant epitopes contribute to clonotype longevity and selection within the peripheral memory T cell pool in the presence of persistent infection with a genetically unstable virus. The Journal of Immunology, 2011, 186: 359-371. C1 [van Bockel, David J.; Munier, Mee Ling; Zaunders, John; Kelleher, Anthony D.] Univ New S Wales, St Vincents Ctr Appl Med Res, Sydney, NSW, Australia. [van Bockel, David J.; Munier, Mee Ling; Cooper, David A.; Kelleher, Anthony D.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Venturi, Vanessa; Greenaway, Hui Yee; Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Price, David A.; Asher, Tedi E.; Douek, Daniel C.] NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. [Price, David A.; Ladell, Kristin] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales. RP van Bockel, DJ (reprint author), St Vincents Ctr Appl Med Res, Level 9,Lowy Packer Bldg,405 Liverpool St, Darlinghurst, NSW 2010, Australia. EM d.vanbockel@cfi.unsw.edu.au RI Zaunders, John/J-6553-2012; Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; OI Zaunders, John/0000-0002-5912-5989; Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Munier, Cynthia/0000-0002-6419-142X FU Australian Government Department of Health and Ageing; National Institutes of Health (Vaccine Research Centre, National Institute of Allergy and Infectious Diseases); Australian National Health and Medical Research Council; Dora Lush (Biomedical) Postgraduate Research Scholarship; Practitioner Fellowship FX This work was supported by the Australian Government Department of Health and Ageing, the Intramural Program of the National Institutes of Health (Vaccine Research Centre, National Institute of Allergy and Infectious Diseases), and the Australian National Health and Medical Research Council via Project and Program grants, a Dora Lush (Biomedical) Postgraduate Research Scholarship (to D. v. B.) and a Practitioner Fellowship (to A. D. K.). D. A. P. is a Medical Research Council (U. K.) Senior Clinical Fellow, V. V. is an Australian Research Council Future Fellow, and M. P. D. is a Sylvia and Charles Viertel Senior Medical Research Fellow. NR 72 TC 25 Z9 25 U1 0 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 359 EP 371 DI 10.4049/jimmunol.1001807 PG 13 WC Immunology SC Immunology GA 699UP UT WOS:000285688700043 PM 21135165 ER PT J AU Lim, JK Obara, CJ Rivollier, A Pletnev, AG Kelsall, BL Murphy, PM AF Lim, Jean K. Obara, Christopher J. Rivollier, Aymeric Pletnev, Alexander G. Kelsall, Brian L. Murphy, Philip M. TI Chemokine Receptor Ccr2 Is Critical for Monocyte Accumulation and Survival in West Nile Virus Encephalitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CRYPTOCOCCUS-NEOFORMANS INFECTION; CENTRAL-NERVOUS-SYSTEM; T-CELL TRAFFICKING; MYCOBACTERIUM-TUBERCULOSIS; INFLAMMATORY MONOCYTES; DISEASE PROGRESSION; BONE-MARROW; IN-VIVO; RECRUITMENT; GENE AB West Nile virus (WNV) is a re-emerging pathogen responsible for outbreaks of fatal meningoencephalitis in humans. Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic deficiency in Ccr2, a chemokine receptor on Ly6c(hi) inflammatory monocytes and other leukocyte subtypes, markedly increases mortality due to WNV encephalitis in C57BL/6 mice; this was associated with a large and selective reduction of Ly6c(hi) monocyte accumulation in the brain. WNV infection in Ccr2(+/+) mice induced a strong and highly selective monocytosis in peripheral blood that was absent in Ccr2(-/-) mice, which in contrast showed sustained monocytopenia. When a 1:1 mixture of Ccr2(+/+) and Ccr2(-/-) donor monocytes was transferred by vein into WNV-infected Ccr2(-/-) recipient mice, monocyte accumulation in the CNS was not skewed toward either component of the mixture, indicating that Ccr2 is not required for trafficking of monocytes from blood to brain. We conclude that Ccr2 mediates highly selective peripheral blood monocytosis during WNV infection of mice and that this is critical for accumulation of monocytes in the brain. The Journal of Immunology, 2011, 186: 471-478. C1 [Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Rivollier, Aymeric; Kelsall, Brian L.] NIAID, Mucosal Immunol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 38 TC 63 Z9 64 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 471 EP 478 DI 10.4049/jimmunol.1003003 PG 8 WC Immunology SC Immunology GA 699UP UT WOS:000285688700054 PM 21131425 ER PT J AU Yao, XL Dai, CL Fredriksson, K Dagur, PK Mccoy, JP Qu, XA Yu, ZX Keeran, KJ Zywicke, GJ Amar, MJA Remaley, AT Levine, SJ AF Yao, Xianglan Dai, Cuilian Fredriksson, Karin Dagur, Pradeep K. McCoy, J. Philip Qu, Xuan Yu, Zu-Xi Keeran, Karen J. Zywicke, Gayle J. Amar, Marcelo J. A. Remaley, Alan T. Levine, Stewart J. TI 5A, an Apolipoprotein A-I Mimetic Peptide, Attenuates the Induction of House Dust Mite-Induced Asthma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; AIRWAY SMOOTH-MUSCLE; RECEPTOR-NULL MICE; CHOLESTEROL EFFLUX; ALTERNATIVE ACTIVATION; ALLERGIC-ASTHMA; T-CELLS; NEGATIVE REGULATOR; ENDOTHELIAL-CELLS; ABCA1 TRANSPORTER AB New treatment approaches are needed for patients with asthma. Apolipoprotein A-I (apoA-I), the major structural protein of high-density lipoproteins, mediates reverse cholesterol transport and has atheroprotective and anti-inflammatory effects. In this study, we hypothesized that an apoA-I mimetic peptide might be effective at inhibiting asthmatic airway inflammation. A 5A peptide, which is a synthetic, bihelical apoA-I mimetic, was administered to wild-type A/J mice via osmotic mini-pump prior to the induction of house dust mite (HDM)-induced asthma. HDM-challenged mice that received the 5A apoA-I mimetic peptide had significant reductions in the number of bronchoalveolar lavage fluid eosinophils, lymphocytes, and neutrophils, as well as in histopathological evidence of airway inflammation. The reduction in airway inflammation was mediated by a reduction in the expression of Th2- and Th17-type cytokines, as well as in chemokines that promote T cell and eosinophil chemotaxis, including CCL7, CCL17, CCL11, and CCL24. Furthermore, the 5A apoA-I mimetic peptide inhibited the alternative activation of pulmonary macrophages in the lungs of HDM-challenged mice. It also abrogated the development of airway hyperresponsiveness and reduced several key features of airway remodeling, including goblet cell hyperplasia and the expression of collagen genes (Col1a1 and Col3a1). Our results demonstrate that the 5A apoA-I mimetic peptide attenuates the development of airway inflammation and airway hyperresponsiveness in an experimental murine model of HDM-induced asthma. These data support the conclusion that strategies using apoA-I mimetic peptides, such as 5A, might be developed further as a possible new treatment approach for asthma. The Journal of Immunology, 2011, 186: 576-583. C1 [Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin; Amar, Marcelo J. A.; Remaley, Alan T.; Levine, Stewart J.] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Dagur, Pradeep K.; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Keeran, Karen J.; Zywicke, Gayle J.] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. [Qu, Xuan; Yu, Zu-Xi] NHLBI, Pathol Core Facil, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Pulm & Vasc Med Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 69 TC 32 Z9 32 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN PY 2011 VL 186 IS 1 BP 576 EP 583 DI 10.4049/jimmunol.1001534 PG 8 WC Immunology SC Immunology GA 699UP UT WOS:000285688700065 PM 21115733 ER PT J AU Jusko, TA De Roos, AJ Schwartz, SM Lawrence, BP Palkovicova, L Nemessanyi, T Drobna, B Fabisikova, A Kocan, A Jahnova, E Kavanagh, TJ Trnovec, T Hertz-Picciotto, I AF Jusko, Todd A. De Roos, Anneclaire J. Schwartz, Stephen M. Lawrence, B. Paige Palkovicova, Lubica Nemessanyi, Tomas Drobna, Beata Fabisikova, Anna Kocan, Anton Jahnova, Eva Kavanagh, Terrance J. Trnovec, Tomas Hertz-Picciotto, Irva TI Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article DE Epidemiology; cohort; DAG; roma ID DEVELOPMENTAL IMMUNOTOXICITY; ENVIRONMENTAL CONTAMINATION; ORGANOCHLORINE PESTICIDES; PCB EXPOSURE; CHILDREN; AUTISM; DIOXINS; ASTHMA; SENSITIZATION; INFECTIONS AB Animal data indicate that developmental tetrachlorodibenzo-p-dioxin exposure alters immune function; however, the potential immunotoxicity of dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) in the developing infant is an understudied area. The aim of the current study is to examine the association between maternal and early postnatal PCB concentrations in relation to total infant serum immunoglobulin concentrations determined at 6-months-of-age. We selected 384 mother-infant pairs participating in a birth cohort study in Eastern Slovakia. PCB concentrations of several congeners were determined in maternal and cord serum samples and in infant serum samples collected at 6-months-of-age using gas chromatography with electron capture detection. Total immunoglobulin (Ig) G, A, and M concentrations were determined by nephelometry, and IgE concentrations were determined by enzyme-linked immunoassay. Linear regression models with adjustment for potential confounding factors were used to estimate the associations between maternal, cord, and 6-month infant PCB concentrations and total serum immunoglobulins. The median maternal serum concentration of PCB-153 was 140 ng/g lipid, approximate to a parts per thousand 10-fold higher than concentrations in childbearing-age women in the United States during the same period. Maternal, cord, or 6-month infant PCB concentrations were not associated with total serum immunoglobulin levels at 6 months, regardless of the timing of PCB exposure, PCB congener, or specific immunoglobulin. In this population, which has high PCB concentrations relative to most populations in the world today, we did not observe any association between maternal and early postnatal PCB concentrations and total immunoglobulin measures of IgG, IgA, IgM, or IgE.Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent known cause of autosomal dominant Parkinson's disease. The LRRK2 gene encodes a Roco protein featuring a Ras of complex proteins (ROC) GTPase and a kinase domain linked by the C-terminal of ROC (COR) domain. Here, we explored the effects of the Y1699C pathogenic LRRK2 mutation in the COR domain on GTPase activity and interactions within the catalytic core of LRRK2. We observed a decrease in GTPase activity for LRRK2 Y1699C comparable to the decrease observed for the R1441C pathogenic mutant and the T1348N dysfunctional mutant. To study the underlying mechanism, we explored the dimerization in the catalytic core of LRRK2. ROC-COR dimerization was significantly weakened by the Y1699C or R1441C/G mutation. Using a competition assay, we demonstrated that the intra-molecular ROC : COR interaction is favoured over ROC : ROC dimerization. Interestingly, the intra-molecular ROC : COR interaction was strengthened by the Y1699C mutation. This is supported by a 3D homology model of the ROC-COR tandem of LRRK2, showing that Y1699 is positioned at the intra-molecular ROC : COR interface. In conclusion, our data provides mechanistic insight into the mode of action of the Y1699C LRRK2 mutant: the Y1699C substitution, situated at the intra-molecular ROC : COR interface, strengthens the intra-molecular ROC : COR interaction, thereby locally weakening the dimerization of LRRK2 at the ROC-COR tandem domain resulting in decreased GTPase activity. C1 [Daniels, Veronique; Lobbestael, Evy; Gao, Fangye; Baekelandt, Veerle; Taymans, Jean-Marc] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Div Mol Med, Dept Mol & Cellular Med, B-3000 Louvain, Belgium. [Vancraenenbroeck, Renee; De Maeyer, Marc] Katholieke Univ Leuven, Lab Biomol Modelling, Div Biochem Mol & Struct Biol, Dept Chem, B-3000 Louvain, Belgium. [Law, Bernard M. H.; Harvey, Kirsten] Univ London, Sch Pharm, Dept Pharmacol, London WC1N 1AX, England. [Greggio, Elisa] Univ Padua, Dept Biol, Padua, Italy. [Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Taymans, JM (reprint author), Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Div Mol Med, Dept Mol & Cellular Med, Kapucijnenvoer 33,VCTB 5, B-3000 Louvain, Belgium. EM jean-marc.taymans@med.kuleuven.be RI Greggio, Elisa/H-6119-2013; Law, Bernard/O-5098-2015 OI Taymans, Jean-Marc/0000-0001-5503-5524; Greggio, Elisa/0000-0002-8172-3598; FU Fund for Scientific Research FWO Vlaanderen [G.0406.06, G. 0666.09]; Institute for the Promotion of Innovation by Science and Technology in Flanders [SBO 80020]; K.U.Leuven [OT/08/052A, IOF-KP/07/001]; Wellcome Trust [WT088145]; NIH, National Institute on Aging FX This work was supported by the Fund for Scientific Research FWO Vlaanderen (G.0406.06, G. 0666.09, postdoctoral fellowship to J-MT and doctoral fellowships to VD, RV and EL), the Institute for the Promotion of Innovation by Science and Technology in Flanders (project SBO 80020), the K.U.Leuven OT/08/052A and IOF-KP/07/001 and the Wellcome Trust (WT088145 to KH). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. We thank Rosa M Sancho for generating LRRK2 YTH constructs. We thank Petri Ollikainen for his contribution in the GTPase assays. NR 47 TC 63 Z9 63 U1 0 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2011 VL 116 IS 2 BP 304 EP 315 DI 10.1111/j.1471-4159.2010.07105.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 695TF UT WOS:000285394800014 PM 21073465 ER PT J AU Biddie, SC AF Biddie, S. C. TI Chromatin Architecture and the Regulation of Nuclear Receptor Inducible Transcription SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE glucocorticoid receptor; nuclear receptor; chromatin; epigenetic; transcription; genome-wide ID NUCLEOSOME CORE PARTICLE; LONG-RANGE INTERACTIONS; VARIANT HISTONE H2A.Z; GENOME-WIDE ANALYSIS; GLUCOCORTICOID-RECEPTOR; DNA METHYLATION; GENE-EXPRESSION; PPAR-GAMMA; CHROMOSOME CONFORMATION; PROGESTERONE-RECEPTOR AB Epigenetic mechanisms alter the structure of local chromosome domains to dynamically regulate gene expression by signalling and propagating transcriptional states. Nuclear receptors, a stimulus-inducible class of transcription factors, interact with chromatin to regulate transcription. To promote transcription, nuclear receptors interact with genomic regulatory elements that are epigenetically marked by modified histone tails, DNA methylation status, histone variants, chromatin accessibility and long-range interactions. Advances in throughput have allowed the profiling of regulatory factor activity on a genome-wide scale, with recent evidence from genomic analyses highlighting novel aspects of DNA-binding factor actions on chromatin. In the present review, the current knowledge of the mechanisms regulating nuclear receptor occupancy at cis-regulatory elements is discussed, with particular emphasis on the glucocorticoid, oestrogen and androgen receptors. Epigenetic regulation of genomic elements direct cell-specific regulatory factor binding and contribute to human variation in factor occupancy. Through regulating nuclear receptor activity, the epigenome is a critical checkpoint in nuclear receptor induced gene expression in health and disease. C1 [Biddie, S. C.] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Fac Med & Dent, Bristol, Avon, England. [Biddie, S. C.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Biddie, SC (reprint author), Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England. EM simon.biddie@bristol.ac.uk OI Biddie, Simon/0000-0002-8253-0253 FU University of Bristol FX The work was supported, in part, by the Needham Cooper Postgraduate Medicine Scholarship, University of Bristol. The author would like to thank Stafford L. Lightman for critically reading the manuscript. NR 134 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JAN PY 2011 VL 23 IS 1 BP 94 EP 106 DI 10.1111/j.1365-2826.2010.02079.x PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 695GE UT WOS:000285357800011 PM 21039975 ER PT J AU Meoli, EM Oh, U Grant, CW Jacobson, S AF Meoli, Elise M. Oh, Unsong Grant, Christian W. Jacobson, Steven TI TGF-beta signaling is altered in the peripheral blood of subjects with multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Multiple sclerosis; Inflammation; TGF-beta; SMAD7 ID GROWTH-FACTOR-BETA; REGULATORY T-CELLS; PROTEOLIPID PROTEIN; GENE-EXPRESSION; DISEASE; CYTOKINE; SMAD7 AB Multiple sclerosis (MS) is a central nervous system inflammatory disorder with evidence of peripheral immune dysregulation. Abnormalities of the immune suppressive cytokine TGF-beta have been reported, but not fully defined, in MS. Through a pathway-focused expression profiling of the peripheral blood, we found abnormalities of TGF-beta RII, SMAD4 and SMAD7 expression in subjects with MS, and reduction in the levels of TGF-beta regulated genes, indicating an overall reduction in TGF-beta signaling in MS. The response to exogenous TGF-beta was intact, however, indicating an extrinsic defect of TGF-beta signaling in MS. These results indicate that TGF-beta control is diminished in MS. Published by Elsevier B.V. C1 [Meoli, Elise M.; Oh, Unsong; Grant, Christian W.; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD USA. RP Jacobson, S (reprint author), 10 Ctr Dr,Bldg 10,Rm 5C103, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov FU NINDS, NIH FX We thank the Drs. Frank Ruscetti, Daniel Bertolette, and Karen Yao for helpful advice. This work was supported by the Intramural Research Program of the NINDS, NIH. NR 21 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN PY 2011 VL 230 IS 1-2 BP 164 EP 168 DI 10.1016/j.jneuroim.2010.10.028 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 717VT UT WOS:000287076200022 PM 21093933 ER PT J AU Kim, KK Byun, E Lee, SK Gaillard, WD Xu, B Theodore, WH AF Kim, K. K. Byun, E. Lee, S. K. Gaillard, W. D. Xu, B. Theodore, W. H. TI Verbal working memory of Korean-English bilinguals An fMRI study SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE Verbal working memory; Korean-English bilingual; Late acquisition; Word recognition task ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; CORTICAL REPRESENTATION; WORD IDENTIFICATION; CONVERGING EVIDENCE; PET INVESTIGATIONS; BRAIN ACTIVATION; NEURAL SYSTEMS; 2ND LANGUAGES; CORTEX AB This study investigated whether different brain areas are involved during working memory tasks related to first (L1) and second (12) languages Functional magnetic resonance imaging (fMRI) was performed on 24 bilingual native Korean speakers who acquired English as their 12 after the age of 12 Their 12 proficiency ranged from low to moderate The Images were acquired while the participants performed word recognition tasks in their L1 and 12 Different areas of activation were identified for Korean and English verbal working memory (KVWM and EVWM) tasks and more right hemisphere activation was found during 12 processing than during L1 processing Direct comparison between activation during L1 and L2 processing revealed that additional hemisphere regions were recruited during the EVWM condition than during the KVWM condition but no significantly greater activation occurred during the KVWM task than during the EVWM task This pattern of results indicates that distinct brain areas are associated with L1 and L2 processing and more diverse and right hemisphere areas are activated during L2 processing compared to L1 processing among low to moderately proficient late bilinguals The activated areas during L2 processing relative to L1 processing were the left precuneus (BA 7) right superior parietal lobule (BA 7) left middle occipital gyrus (BA 19) and left cerebellum suggesting that participants might rely more on visual cues and visual processing for word recoding and visual analysis during L2 processing than during L1 processing It is also plausible that participants engaged in attention-based rehearsal during L2 processing Published by Elsevier Ltd C1 [Gaillard, W. D.; Theodore, W. H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Xu, B.] NIH, Human Cort Physiol & Stroke Neurorehabil Sect, Bethesda, MD 20892 USA. [Kim, K. K.; Byun, E.] Dongguk Univ, Int Hosp, Dept Neurol, Goyang Si, Gyeonggi Do, South Korea. [Lee, S. K.] Seoul Natl Univ Hosp, Dept Neurol, Seoul 110744, South Korea. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, Bldg 10,Room 5N 250,10 Ctr Dr, Bethesda, MD 20892 USA. FU Ministry of Education Science and Technology (MEST) [KRF-2007-331-H0006] FX This work was supported by Basic Science ResearchProgram through the Korea Research Foundation (KRF) funded by the Ministry of Education Science and Technology (MEST) (KRF-2007-331-H0006) NR 74 TC 4 Z9 4 U1 4 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD JAN PY 2011 VL 24 IS 1 BP 1 EP 13 DI 10.1016/j.jneuroling.2010.07.001 PG 13 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 682FS UT WOS:000284387400001 ER PT J AU Joiner, WM Ajayi, O Sing, GC Smith, MA AF Joiner, Wilsaan M. Ajayi, Obafunso Sing, Gary C. Smith, Maurice A. TI Linear Hypergeneralization of Learned Dynamics Across Movement Speeds Reveals Anisotropic, Gain-Encoding Primitives for Motor Adaptation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID FRONTAL EYE FIELDS; SUPERIOR COLLICULUS; REACHING MOVEMENTS; INTERNAL-MODELS; INVERSE MODELS; ARM MOVEMENTS; DIRECTION; VELOCITY; REPRESENTATION; AMPLITUDE AB Joiner WM, Ajayi O, Sing GC, Smith MA. Linear hypergeneralization of learned dynamics across movement speeds reveals anisotropic, gain-encoding primitives for motor adaptation. J Neurophysiol 105: 45-59, 2011. First published September 29, 2010; doi:10.1152/jn.00884.2009. The ability to generalize learned motor actions to new contexts is a key feature of the motor system. For example, the ability to ride a bicycle or swing a racket is often first developed at lower speeds and later applied to faster velocities. A number of previous studies have examined the generalization of motor adaptation across movement directions and found that the learned adaptation decays in a pattern consistent with the existence of motor primitives that display narrow Gaussian tuning. However, few studies have examined the generalization of motor adaptation across movement speeds. Following adaptation to linear velocity-dependent dynamics during point-to-point reaching arm movements at one speed, we tested the ability of subjects to transfer this adaptation to short-duration higher-speed movements aimed at the same target. We found near-perfect linear extrapolation of the trained adaptation with respect to both the magnitude and the time course of the velocity profiles associated with the high-speed movements: a 69% increase in movement speed corresponded to a 74% extrapolation of the trained adaptation. The close match between the increase in movement speed and the corresponding increase in adaptation beyond what was trained indicates linear hypergeneralization. Computational modeling shows that this pattern of linear hypergeneralization across movement speeds is not compatible with previous models of adaptation in which motor primitives display isotropic Gaussian tuning of motor output around their preferred velocities. Instead, we show that this generalization pattern indicates that the primitives involved in the adaptation to viscous dynamics display anisotropic tuning in velocity space and encode the gain between motor output and motion state rather than motor output itself. C1 [Ajayi, Obafunso; Sing, Gary C.; Smith, Maurice A.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Joiner, Wilsaan M.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St, Cambridge, MA 02138 USA. EM mas@seas.harvard.edu FU Alfred P. Sloan Foundation; McKnight Endowment for Neuroscience FX This work was supported by the Sloan Research Fellowship from the Alfred P. Sloan Foundation and a Scholar Award from the McKnight Endowment for Neuroscience to M. A. Smith. NR 57 TC 16 Z9 16 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2011 VL 105 IS 1 BP 45 EP 59 DI 10.1152/jn.00884.2009 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 705MU UT WOS:000286139900006 PM 20881197 ER PT J AU Won, YJ Ono, F Ikeda, SR AF Won, Yu-Jin Ono, Fumihito Ikeda, Stephen R. TI Identification and Modulation of Voltage-Gated Ca2+ Currents in Zebrafish Rohon-Beard Neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; ROOT GANGLION NEURONS; G-PROTEIN MODULATION; BETA-GAMMA-SUBUNITS; CALCIUM-CHANNELS; N-TYPE; SYMPATHETIC NEURONS; DEPENDENT MODULATION; EMBRYONIC ZEBRAFISH; LARVAL ZEBRAFISH AB Won YJ, Ono F, Ikeda SR. Identification and modulation of voltagegated Ca2+ currents in zebrafish Rohon-Beard neurons. J Neurophysiol 105: 442-453, 2011. First published October 20, 2010; doi:10.1152/jn.00625.2010. Electrically excitable cells have voltage-dependent ion channels on the plasma membrane that regulate membrane permeability to specific ions. Voltage-gated Ca2+ channels (VGCCs) are especially important as Ca2+ serves as both a charge carrier and second messenger. Zebrafish (Danio rerio) are an important model vertebrate for studies of neuronal excitability, circuits, and behavior. However, electrophysiological properties of zebrafish VGCCs remain largely unexplored because a suitable preparation for whole cell voltage-clamp studies is lacking. Rohon-Beard (R-B) sensory neurons represent an attractive candidate for this purpose because of their relatively large somata and functional homology to mammalian dorsal root ganglia (DRG) neurons. Transgenic zebrafish expressing green fluorescent protein in R-B neurons, (Isl2b:EGFP)(ZC7), were used to identify dissociated neurons suitable for whole cell patch-clamp experiments. Based on biophysical and pharmacological properties, zebrafish R-B neurons express both high-and low-voltage-gated Ca2+ current (HVA- and LVA-I-Ca, respectively). Ni+-sensitive LVA-I-Ca occur in the minority of R-B neurons (30%) and omega-conotoxin GVIA-sensitive Ca(V)2.2 (N-type) Ca2+ channels underlie the vast majority (90%) of HVA-I-Ca. To identify G protein coupled receptors (GPCRs) that modulate HVA-I-Ca, a panel of neurotransmitters was screened. Application of GABA/baclofen or serotonin produced a voltage-dependent inhibition while application of the mu-opioid agonist DAMGO resulted in a voltage-independent inhibition. Unlike in mammalian neurons, GPCR-mediated voltage-dependent modulation of I-Ca appears to be transduced primarily via a cholera toxin-sensitive G alpha subunit. These results provide the basis for using the zebrafish model system to understanding Ca2+ channel function, and in turn, how Ca2+ channels contribute to mechanosensory function. C1 [Won, Yu-Jin; Ikeda, Stephen R.] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Ono, Fumihito] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Fishers Lane 5625,Room TS-11,MSC 9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508 FU National Institutes of Health-National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Research Program of the National Institutes of Health-National Institute on Alcohol Abuse and Alcoholism. NR 62 TC 8 Z9 8 U1 2 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2011 VL 105 IS 1 BP 442 EP 453 DI 10.1152/jn.00625.2010 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 705MU UT WOS:000286139900037 PM 20962070 ER PT J AU Li, LL Padhi, A Ranjeva, SL Donaldson, SC Ware, BC Mugamba, J Johnson, D Opio, Z Jayarao, B Kapur, V Poss, M Schiff, SJ AF Li, Lingling Padhi, Abinash Ranjeva, Sylvia L. Donaldson, Sarah C. Ware, Benjamin C. Mugamba, John Johnson, Derek Opio, Zephana Jayarao, Bhushan Kapur, Vivek Poss, Mary Schiff, Steven J. TI Association of bacteria with hydrocephalus in Ugandan infants Clinical article SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE hydrocephalus; central nervous system infection; tropical medicine; pediatrics; developing country ID ENDOSCOPIC 3RD VENTRICULOSTOMY; NEONATAL MENINGITIS; DEVELOPING-COUNTRIES; DEXAMETHASONE; IDENTIFICATION; SEPTICEMIA; NEWBORN; SEPSIS; MODEL AB Object. Infantile hydrocephalus in East Africa is predominantly postinfectious. The microbial origins remain elusive, since most patients present with postinfectious hydrocephalus after antecedent neonatal sepsis (NS) has resolved. Methods. To characterize this syndrome in Ugandan infants, the authors used polymerase chain reaction targeting bacterial 16S ribosomal DNA from CSF to determine if bacterial residua from recent infections were detectable. Bacteria were identified based on the relationship of genetic sequences obtained with reference bacteria in public databases. The authors evaluated samples from patients presenting during dry and rainy seasons and performed environmental sampling in the villages of patients. Results. Bacterial DNA was recovered from 94% of patients. Gram-negative bacteria in the phylum Proteobacteria were the most commonly detected. Within this phylum, Gammaproteobacteria dominated in patients presenting after infections during the rainy season, and Betaproteobacteria was most common following infections during the dry season. Acinetobacter species were identified in the majority of patients admitted after rainy season infection. Conclusions. Postinfectious hydrocephalus in Ugandan infants appears associated with predominantly enteric gram-negative bacteria. These findings highlight the need for linking these cases with antecedent NS to develop more effective treatment and prevention strategies. (DOI: 10.3171/2010.9.PEDS10162) C1 [Schiff, Steven J.] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA. [Li, Lingling; Donaldson, Sarah C.; Jayarao, Bhushan; Kapur, Vivek; Poss, Mary] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Padhi, Abinash; Poss, Mary] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Ranjeva, Sylvia L.; Schiff, Steven J.] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA. [Schiff, Steven J.] Penn State Univ, Dept Neurosurg, University Pk, PA 16802 USA. [Schiff, Steven J.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA. [Ware, Benjamin C.] Childrens Hosp Boston, Dept Neurosurg, Boston, MA USA. [Mugamba, John; Johnson, Derek; Opio, Zephana] CURE Childrens Hosp Uganda, Mbale, Uganda. [Poss, Mary] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Schiff, SJ (reprint author), Penn State Univ, Ctr Neural Engn, 212 Earth Engn Sci Bldg, University Pk, PA 16802 USA. EM sschiff@psu.edu RI Kapur, Vivek/F-7610-2013; OI Kapur, Vivek/0000-0002-9648-0138 FU Penn State Clinical and Translational Sciences Institute FX This work was supported by a grant from the Penn State Clinical and Translational Sciences Institute and by the generosity of the endowment funds of Harvey F. Brush. NR 32 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD JAN PY 2011 VL 7 IS 1 BP 73 EP 87 DI 10.3171/2010.9.PEDS10162 PG 15 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 699NH UT WOS:000285669600015 PM 21194290 ER PT J AU Owen, DRJ Gunn, RN Rabiner, EA Bennacef, I Fujita, M Kreisl, WC Innis, RB Pike, VW Reynolds, R Matthews, PM Parker, CA AF Owen, David R. J. Gunn, Roger N. Rabiner, Eugenii A. Bennacef, Idriss Fujita, Masahiro Kreisl, William C. Innis, Robert B. Pike, Victor W. Reynolds, Richard Matthews, Paul M. Parker, Christine A. TI Mixed-Affinity Binding in Humans with 18-kDa Translocator Protein Ligands SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE TSPO; mixed-affinity binding; radioligand binding ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; HUMAN BRAIN; PET; RADIOLIGAND AB (11)C-PBR28 PET can detect the 18-kDa translocator protein (TSPO) expressed within macrophages. However, quantitative evaluation of the signal in brain tissue from donors with multiple sclerosis (MS) shows that PBR28 binds the TSPO with high affinity (binding affinity [K(i)], similar to 4 nM), low affinity (K(i), similar to 200 nM), or mixed affinity (2 sites with K(i), similar to 4 nM and similar to 300 nM). Our study tested whether similar binding behavior could be detected in brain tissue from donors with no history of neurologic disease, with TSPO-binding PET ligands other than (11)C-PBR28, for TSPO present in peripheral blood, and with human brain PET data acquired in vivo with (11)C-PBR28. Methods: The affinity of TSPO ligands was measured in the human brain post-mortem from donors with a history of MS (n = 13), donors without any history of neurologic disease (n = 20), and in platelets from healthy volunteers (n = 3). Binding potential estimates from thirty-five (11)C-PBR28 PET scans from an independent sample of healthy volunteers were analyzed using a gaussian mixture model. Results: Three binding affinity patterns were found in brains from subjects without neurologic disease in similar proportions to those reported previously from studies of MS brains. TSPO ligands showed substantial differences in affinity between subjects classified as high-affinity binders (HABs) and low-affinity binders (LABs). Differences in affinity between HABs and LABs are approximately 50-fold with PBR28, approximately 17-fold with PBR06, and approximately 4-fold with DAA1106, DPA713, and PBR111. Where differences in affinity between HABs and LABs were low (similar to 4-fold), distinct affinities were not resolvable in binding curves for mixed-affinity binders (MABs), which appeared to express 1 class of sites with an affinity approximately equal to the mean of those for HABs and LABs. Mixed-affinity binding was detected in platelets from an independent sample (HAB, 69%; MAB, 31%), although LABs were not detected. Analysis of (11)C-PBR28 PET data was not inconsistent with the existence of distinct subpopulations of HABs, MABs, and LABs. Conclusion: With the exception of (11)C-PK11195, all TSPO PET ligands in current clinical application recognize HABs, LABs, and MABs in brain tissue in vitro. Knowledge of subjects' binding patterns will be required to accurately quantify TSPO expression in vivo using PET. C1 [Owen, David R. J.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Expt Med, London W12 0NN, England. [Owen, David R. J.; Gunn, Roger N.; Rabiner, Eugenii A.; Bennacef, Idriss; Matthews, Paul M.; Parker, Christine A.] GSK Clin Imaging Ctr, London, England. [Gunn, Roger N.; Rabiner, Eugenii A.; Matthews, Paul M.] Univ London Imperial Coll Sci Technol & Med, Ctr Neurosci, London W12 0NN, England. [Fujita, Masahiro; Kreisl, William C.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Reynolds, Richard] Univ London Imperial Coll Sci Technol & Med, Wolfson Neurosci Labs, London W12 0NN, England. RP Owen, DRJ (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Expt Med, London W12 0NN, England. EM d.owen@imperial.ac.uk RI Gunn, Roger/H-1666-2012; Rabiner, Eugenii/G-6263-2012; OI Gunn, Roger/0000-0003-1181-5769; Rabiner, Eugenii/0000-0003-3612-6687; Owen, David/0000-0002-1198-7563; Matthews, Paul M/0000-0002-1619-8328 FU Imperial College; Wellcome Trust; National Institute of Mental Health (NIMH); GlaxoSmithKline FX We thank the U.K. Multiple Sclerosis Tissue Bank and Chris Rhodes for providing all human tissue used in this study. This work is supported by GlaxoSmithKline, Imperial College, the Wellcome Trust, and the Intramural Research Program of the National Institute of Mental Health (NIMH). NR 13 TC 126 Z9 126 U1 1 U2 21 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN 1 PY 2011 VL 52 IS 1 BP 24 EP 32 DI 10.2967/jnumed.110.079459 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 699TT UT WOS:000285686400010 PM 21149489 ER PT J AU Sun, XL Yan, YJ Liu, SL Cao, QZ Yang, M Neamati, N Shen, BZ Niu, G Chen, XY AF Sun, Xilin Yan, Yongjun Liu, Shuanglong Cao, Qizhen Yang, Min Neamati, Nouri Shen, Baozhong Niu, Gang Chen, Xiaoyuan TI F-18-FPPRGD2 and F-18-FDG PET of Response to Abraxane Therapy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE therapy response; positron emission tomography (PET); Abraxane; F-18-FDG; RGD ID ALBUMIN-BOUND PACLITAXEL; SQUAMOUS-CELL CARCINOMA; INTEGRIN ALPHA(V)BETA(3) EXPRESSION; SMALL-ANIMAL PET; BREAST-CANCER; TUMOR ANGIOGENESIS; RGD; ANTITUMOR; HEAD; NECK AB Abraxane (nanoparticle albumin-bound paclitaxel) is an anticancer drug approved by the Food and Drug Administration. However, the mechanism of action of Abraxane is complex, and no established biomarker is available to accurately monitor its treatment outcomes. The aim of this study was to investigate whether the integrin-specific PET tracer F-18-FPPRGD2 (investigational new drug 104150) can be used to monitor early response of tumors to Abraxane therapy. Methods: Orthotopic MDA-MB-435 breast cancer mice were treated with Abraxane (25 mg/kg every other day, 3 doses) or phosphate-buffered saline. Tumor volume was monitored by caliper measurement. PET scans were obtained before and at different times after the start of treatment (days 0, 3, 7, 14, and 21) using F-18-FPPRGD2 and F-18-FDG. The tumoricidal effect was also assessed ex vivo by immunohistochemistry. Results: Abraxane treatment inhibited the tumor growth, and a significant difference in tumor volume could be seen at day 5 after the initiation of treatment. The tumor uptake of F-18-FPPRGD2 in the Abraxane-treated group was significantly lower on days 3 and 7 than at baseline but returned to the baseline level at days 14 and 21, indicative of relapse of the tumors after the treatment was halted. Immunohistologic staining confirmed that the change of F-18-FPPRGD2 uptake correlated with the variation of integrin level in the tumor vasculature induced by Abraxane treatment. No significant change of tumor (rather than vascular) integrin expression was observed throughout the study. No significant decrease of F-18-FDG uptake was found between the treated and the control tumors on days 3, 14, and 21, although an increase in F-18-FDG tumor uptake of treated mice, as compared with the control mice, was found on day 7. The increase of F-18-FDG on day 7 was related to the inflammatory response during therapy. Conclusion: Abraxane-mediated downregulation of integrin alpha v beta 3 expression on tumor endothelial cells can be quantitatively visualized by PET. The change of integrin expression precedes that of tumor size. Consequently, F-18-FPPRGD2 PET is superior to F-18-FDG PET in monitoring early response to treatment, favoring its potential clinical translation. C1 [Sun, Xilin; Yan, Yongjun; Yang, Min; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Sun, Xilin; Shen, Baozhong] Harbin Med Coll, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin, Peoples R China. [Liu, Shuanglong; Cao, Qizhen] Stanford Univ, Sch Med, Dept Radiol, MIPS, Stanford, CA 94305 USA. [Neamati, Nouri] Univ So Calif, Sch Pharm, Los Angeles, CA USA. [Niu, Gang] Natl Inst Biomed Imaging & Bioengn, Imaging Sci Training Program, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 31 Ctr Dr,1C22, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); Radiology and Imaging Sciences Department, NIH Clinical Center FX We thank Dr. Henry S. Eden for proofreading this manuscript. This project was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); the Radiology and Imaging Sciences Department, NIH Clinical Center; and the Intramural Research Program, NIBIB, NIH. NR 39 TC 43 Z9 46 U1 1 U2 16 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN 1 PY 2011 VL 52 IS 1 BP 140 EP 146 DI 10.2967/jnumed.110.080606 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 699TT UT WOS:000285686400027 PM 21149494 ER PT J AU Davis, CD Milner, JA AF Davis, Cindy D. Milner, John A. TI Nutrigenomics, Vitamin D and Cancer Prevention SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Review DE Vitamin D; Cancer prevention; Vitamin D receptor; Nutrigenomics; Biomarkers; Polymorphisms ID D-RECEPTOR GENE; D-ENDOCRINE SYSTEM; PROSTATE-CANCER; 1,25-DIHYDROXYVITAMIN D-3; COLON-CANCER; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; PANCREATIC-CANCER; CELL-LINE; BODY-FAT; 25-HYDROXYVITAMIN D-1-ALPHA-HYDROXYLASE AB Although there is growing epidemiological, preclinical and clinical evidence suggesting that low vitamin D intake, exposure and/or status is associated with an increased risk of various types of cancer, the optimum amount needed remains controversial. Furthermore, there is evidence that a U- or J-shaped response curve exist between 25(OH)D and certain cancers. Increasing information about the impact of genetic variation, especially polymorphisms that influence absorption, transport, metabolism and associated molecular targets, should help clarify inconsistencies in the data regarding vitamin D's effect on cancer risk. Rather than focusing on the main effects of a few variants of these genes alone, future studies need to consider gene-nutrient or environmental interactions. Nutrigenomics should clarify who might benefit and be placed at risk because of vitamin D exposure. Copyright (C) 2011 S. Karger AG, Basel C1 [Davis, Cindy D.] NCI, Canc Prevent Div, Nutr Sci Res Grp, Bethesda, MD 20892 USA. RP Davis, CD (reprint author), NCI, Canc Prevent Div, Nutr Sci Res Grp, 6130 Executive Blvd,Suite 3159, Bethesda, MD 20892 USA. EM davisci@mail.nih.gov NR 90 TC 14 Z9 17 U1 0 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 EI 1661-6758 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2011 VL 4 IS 1 BP 1 EP 11 DI 10.1159/000324175 PG 11 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 766JD UT WOS:000290777500001 PM 21430387 ER PT J AU Fenech, M El-Sohemy, A Cahill, L Ferguson, LR French, TAC Tai, ES Milner, J Koh, WP Xie, L Zucker, M Buckley, M Cosgrove, L Lockett, T Fung, KYC Head, R AF Fenech, Michael El-Sohemy, Ahmed Cahill, Leah Ferguson, Lynnette R. French, Tapaeru-Ariki C. Tai, E. Shyong Milner, John Koh, Woon-Puay Xie, Lin Zucker, Michelle Buckley, Michael Cosgrove, Leah Lockett, Trevor Fung, Kim Y. C. Head, Richard TI Nutrigenetics and Nutrigenomics: Viewpoints on the Current Status and Applications in Nutrition Research and Practice SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Review DE Dietetics; Nutrigenetics; Nutrigenomics; Nutrition Research; Personalised nutrition ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; GENOME-HEALTH NUTRIGENOMICS; CANCER PREVENTION RESEARCH; PROTEIN-COUPLED RECEPTOR; ADVERSE DRUG-REACTIONS; CHAIN FATTY-ACIDS; COLORECTAL-CANCER; GENE-EXPRESSION; FTO GENE AB Nutrigenetics and nutrigenomics hold much promise for providing better nutritional advice to the public generally, genetic subgroups and individuals. Because nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and ever new 'omic' technologies, it is often difficult, even for educated professionals, to appreciate their relevance to the practice of preventive approaches for optimising health, delaying onset of disease and diminishing its severity. This review discusses (i) the basic concepts, technical terms and technology involved in nutrigenetics and nutrigenomics; (ii) how this emerging knowledge can be applied to optimise health, prevent and treat diseases; (iii) how to read, understand and interpret nutrigenetic and nutrigenomic research results, and (iv) how this knowledge may potentially transform nutrition and dietetic practice, and the implications of such a transformation. This is in effect an up-to-date overview of the various aspects of nutrigenetics and nutrigenomics relevant to health practitioners who are seeking a better understanding of this new frontier in nutrition research and its potential application to dietetic practice. Copyright (C) 2011 S. Karger AG, Basel C1 [Fenech, Michael; Zucker, Michelle; Buckley, Michael; Cosgrove, Leah; Lockett, Trevor; Fung, Kim Y. C.; Head, Richard] CSIRO Preventat Hlth Natl Res Flagship, Adelaide, SA 5000, Australia. [El-Sohemy, Ahmed; Cahill, Leah] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. [Ferguson, Lynnette R.; French, Tapaeru-Ariki C.] Univ Auckland, Discipline Nutr, Fac Med & Hlth Sci, Auckland 1, New Zealand. [Milner, John] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Rockville, MD USA. [Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore. [Koh, Woon-Puay] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore. [Xie, Lin] Jilin Univ, Dept Nutr & Food Hyg, Sch Publ Hlth, Changchun 130023, Peoples R China. [Ferguson, Lynnette R.; French, Tapaeru-Ariki C.] Nutrigen New Zealand, Auckland, New Zealand. RP Fenech, M (reprint author), CSIRO Preventat Hlth Natl Res Flagship, Adelaide, SA 5000, Australia. EM michael.fenech@csiro.au RI Ferguson, Lynnette/F-5989-2011; Head, Richard/G-3918-2012; Fung, Kim/H-3522-2013; Lockett, Trevor/H-8970-2013; OI Tai, E Shyong/0000-0003-2929-8966; Head, Richard/0000-0002-1196-0926; Fung, Kim/0000-0002-7205-4206; Lockett, Trevor/0000-0002-8063-071X; El-Sohemy, Ahmed/0000-0002-8877-6414 FU Foundation for Research Science and Technology FX Boon Yee Yeong and Mia Isabelle (both from ILSI South East Asia) are acknowledged for organising the symposium 'Fundamentals of Nutrigenetics/Nutrigenomics and Its Applications' in 2009, which led to the writing of this review. Nutrigenomics New Zealand is a collaboration between AgResearch Ltd., Crop & Food Research, HortResearch and the University of Auckland, with funding through the Foundation for Research Science and Technology. NR 108 TC 60 Z9 68 U1 3 U2 54 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2011 VL 4 IS 2 BP 69 EP 89 DI 10.1159/000327772 PG 21 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 797YT UT WOS:000293166900002 PM 21625170 ER PT J AU Regan, KS Wambogo, EA Haggans, CJ AF Regan, Karen S. Wambogo, Edwina A. Haggans, Carol J. TI NIH and USDA Funding of Dietary Supplement Research, 1999-2007 SO JOURNAL OF NUTRITION LA English DT Article AB Over one-half of U.S. adults use dietary supplements, so federally supported research into the safety and effectiveness of these compounds is important for the health of many Americans. Data collected in the Computer Access to Research on Dietary Supplements database, which compiles federally sponsored dietary supplement-related research, are useful to scientists in determining the type of dietary supplement research that federal agencies are currently funding and where research gaps exist. This wide describes the dietary Supplement-related research funded by the NIH and the USDA. Between fiscal years 1999 aid 2007, the number of research projects and funding for dietary supplement research more than doubled. During that period, NIH funded 6748 dietary supplement-related projects at a cost of $1.9 billion and the USDA funded 2258 projects at a cost of $347 million. The top funded dietary supplement ingredient categories were vitamins and minerals, botanicals, phytochemicals, and fatty acids. Cancer was by far the most frequent health outcome in dietary supplement research funding, nearly double the next closest health outcome category. Other health outcomes with the greatest funding were cellular and molecular mechanisms, cardiovascular health, women's reproductive health, and immune function. The greatest number of dietary supplement research projects are funded by the NIH National Cancer Institute, the NIH National Center for Complementary and Alternative Medicine; the NIH Office of Dietary Supplements, and the USDA Agricultural Research Service. J. Nutr. 141: 1-3, 2011. C1 [Regan, Karen S.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Wambogo, Edwina A.; Haggans, Carol J.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Regan, KS (reprint author), NIH, Div Nutr Res Coordinat, Bldg 10, Bethesda, MD 20892 USA. EM kr184x@nih.gov NR 6 TC 3 Z9 4 U1 0 U2 0 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2011 VL 141 IS 1 BP 1 EP 3 DI 10.3945/jn.110.134106 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 702KS UT WOS:000285893900001 PM 21106929 ER PT J AU Gilsanz, V Chalfant, J Kalkwarf, H Zemel, B Lappe, J Oberfield, S Shepherd, J Wren, T Winer, K AF Gilsanz, Vicente Chalfant, James Kalkwarf, Heidi Zemel, Babette Lappe, Joan Oberfield, Sharon Shepherd, John Wren, Tishya Winer, Karen TI Age at Onset of Puberty Predicts Bone Mass in Young Adulthood SO JOURNAL OF PEDIATRICS LA English DT Article ID ANDROGEN INSENSITIVITY SYNDROME; MINERAL DENSITY; AROMATASE DEFICIENCY; CONSTITUTIONAL DELAY; RECEPTOR GENE; SHORT STATURE; MEN; OSTEOPOROSIS; FEMALES; GROWTH AB Objective To determine whether the commencement and length of puberty influences dual x-ray absorptiometry (DXA) values of bone mineral content (BMC) and bone mineral density (BMD) in the axial and appendicular skeleton at skeletal maturity. Study design From the Bone Mineral Density in Childhood Study, we identified children who began puberty and completed sexual and skeletal development and examined whether the timing and length of puberty influence DXA values of BMC and BMD at skeletal maturity. Results A total of 78 girls and 85 boys began puberty and completed skeletal maturity; 4.4 +/- 0.8 and 4.5 +/- 0.8 years later, respectively. Multiple linear regression analyses indicated that the age of onset of puberty was a strong negative predictor of DXA bone measurements at skeletal maturity, independent of bone values at the beginning of puberty, and the length of puberty. This negative relation was observed for all BMC and BMD measurements at all skeletal sites, in both boys and girls (all P < .0001). In contrast, length of puberty had no relation to any measures of bone. Conclusions In healthy adolescent males and females, bone mass and bone density at skeletal maturity are inversely related to the timing of puberty. (J Pediatr 2011; 158:52-7). C1 [Gilsanz, Vicente] Childrens Hosp Los Angeles, Dept Radiol, Los Angeles, CA 90027 USA. [Shepherd, John] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kalkwarf, Heidi] Cincinnati Childrens Med Ctr, Cincinnati, OH USA. [Zemel, Babette] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Lappe, Joan] Creighton Univ, Omaha, NE 68178 USA. [Oberfield, Sharon] Columbia Univ, New York, NY USA. [Winer, Karen] NICHHD, Bethesda, MD 20892 USA. RP Gilsanz, V (reprint author), Childrens Hosp Los Angeles, Dept Radiol, MS 81,4650 Sunset Blvd, Los Angeles, CA 90027 USA. EM vgilsanz@chla.usc.edu RI Zemel, Babette/D-1117-2009 FU National Institute of Child Health and Human Development (NICHD) [NO1-HD-1-3228, -3329, -3330, -3331, -3332, -3333] FX Funded by the National Institute of Child Health and Human Development (NICHD) contracts NO1-HD-1-3228, -3329, -3330, -3331, -3332, and -3333. The authors declare no conflicts of interest. NR 29 TC 32 Z9 32 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2011 VL 158 IS 1 BP 52 EP + DI 10.1016/j.jpeds.2010.06.054 PG 8 WC Pediatrics SC Pediatrics GA 692OG UT WOS:000285161500013 PM 20797727 ER PT J AU Munch, S Korst, LM Hernandez, GD Romero, R Goodwin, TM AF Munch, S. Korst, L. M. Hernandez, G. D. Romero, R. Goodwin, T. M. TI Health-related quality of life in women with nausea and vomiting of pregnancy: the importance of psychosocial context SO JOURNAL OF PERINATOLOGY LA English DT Article DE hyperemesis gravidarum; nausea; vomiting; pregnancy; quality of life ID HYPEREMESIS GRAVIDARUM; DEPRESSIVE SYMPTOMS; EXPERIENCES; BURDEN; IMPACT AB Objective: To test whether women with hyperemesis gravidarum (HG) demonstrated lower health-related quality of life (HRQoL) scores compared with those with nausea and vomiting of pregnancy (NVP). Study Design: Women with HG or NVP were examined during the first trimester. Multivariate models identified characteristics of women at risk for low HRQoL, as measured by an NVP-specific HRQoL test and a generic HRQoL test, the Short Form (SF)-36. Result: Although the SF-36 assessment did not discriminate between the two groups, the NVP-specific test showed that women with HG (N=29) were 3-6 times more likely than women with NVP (N=48) to have low HRQoL. Both tests demonstrated that perceived physical symptoms and multiple psychosocial factors, such as depression and marital status, seemed to be equally or more important than having HG. Conclusion: Although a low HRQoL was associated with an HG diagnosis, multiple physical symptoms and psychosocial factors placed both groups of women at risk. Journal of Perinatology (2011) 31, 10-20; doi:10.1038/jp.2010.54; published online 22 April 2010 C1 [Munch, S.] Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08901 USA. [Korst, L. M.; Hernandez, G. D.; Goodwin, T. M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Romero, R.] NICHD, Perinatol Res Branch, NIH, Detroit, MI USA. RP Munch, S (reprint author), Rutgers State Univ, Sch Social Work, 536 George St, New Brunswick, NJ 08901 USA. EM munch@ssw.rutgers.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services [N01-HD-2-3342] FX This study was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, contract number N01-HD-2-3342. NR 45 TC 28 Z9 29 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD JAN PY 2011 VL 31 IS 1 BP 10 EP 20 DI 10.1038/jp.2010.54 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 699WR UT WOS:000285694100002 PM 20410906 ER PT J AU Kitanaka, J Kitanaka, N Hall, FS Uhl, GR Tanaka, K Tatsuta, T Morita, Y Nishiyama, N Takemura, M AF Kitanaka, Junichi Kitanaka, Nobue Hall, F. Scott Uhl, George. R. Tanaka, Koh-ichi Tatsuta, Tomohiro Morita, Yoshio Nishiyama, Nobuyoshi Takemura, Motohiko TI Alterations in hypothalamic histamine levels are associated with expression frequency of methamphetamine-induced stereotypical biting in mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 84th Annual Meeting of the Japanese-Pharmacological-Society/11th Southeast Asian Western Pacific Regional Meeting of Pharmacologists CY MAR 22-24, 2011 CL Yokohama, JAPAN SP Japanese Pharmacolog Soc C1 [Kitanaka, Junichi; Kitanaka, Nobue; Takemura, Motohiko] Hyogo Med Col, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan. [Hall, F. Scott; Uhl, George. R.] NIDA, IRP, NIH, DHHS, Baltimore, MD 21224 USA. [Tanaka, Koh-ichi; Nishiyama, Nobuyoshi] Hyogo Univ Hlth Sci, Sch Pharm, Dept Pharm, Div Pharmacol, Kobe, Hyogo 6508530, Japan. [Tatsuta, Tomohiro] Ibogawa Hosp, Tatsuno, Hyogo 6711688, Japan. [Morita, Yoshio] Baika Womens Univ, Fac Nursing, Osaka 5678578, Japan. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2011 VL 115 SU 1 BP 250P EP 250P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 743QU UT WOS:000289034601384 ER PT J AU Butler, EN Ambs, AMH Reedy, J Bowles, HR AF Butler, Ebonee N. Ambs, Anita M. H. Reedy, Jill Bowles, Heather R. TI Identifying GIS Measures of the Physical Activity Built Environment Through a Review of the Literature SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE geospatial; neighborhood; obesity; community design ID NEIGHBORHOOD WALKABILITY; OBJECTIVE MEASURES; URBAN DESIGN; WALKING; ADULTS; TRANSPORTATION; ASSOCIATIONS; DESTINATIONS; BEHAVIOR; DENSITY AB Background: Examining relationships between features of the built environment and physical activity is achievable with geographic information systems technology (GIS). The purpose of this paper is to review the literature to identify GIS measures that can be considered for inclusion in national public health surveillance efforts. In the absence of a universally agreed upon framework that integrates physical, social, and cultural aspects of the environment, we used a multidimensional model of access to synthesize the literature. Methods: We identified 29 studies published between 2005 and 2009 with physical activity outcomes that included 1 or more built environment variables measured using GIS. We sorted built environment measures into 5 dimensions of access: accessibility, availability, accommodation, affordability, and acceptability. Results: Geospatial land-use data, street network data, environmental audits, and commercial databases can be used to measure the availability, accessibility, and accommodation dimensions of access. Affordability and acceptability measures rely on census and self-report data. Conclusions: GIS measures have been included in studies investigating the built environment and physical activity, although few have examined more than I construct of access. Systematic identification and collection of relevant GIS measures can facilitate collaboration and accelerate the advancement of research on the built environment and physical activity. C1 [Butler, Ebonee N.; Ambs, Anita M. H.; Reedy, Jill; Bowles, Heather R.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Butler, EN (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 51 TC 10 Z9 11 U1 4 U2 29 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2011 VL 8 SU 1 BP S91 EP S97 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 707KZ UT WOS:000286286600012 PM 21350268 ER PT J AU McKinnon, RA Bowles, HR Trowbridge, MJ AF McKinnon, Robin A. Bowles, Heather R. Trowbridge, Matthew J. TI Engaging Physical Activity Policymakers SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Editorial Material ID BUILT ENVIRONMENT; NATIONAL PLAN; UNITED-STATES; HEALTH; TRANSPORTATION; PREVENTION; OBESITY; SECTOR C1 [McKinnon, Robin A.; Bowles, Heather R.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Trowbridge, Matthew J.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP McKinnon, RA (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 30 TC 4 Z9 4 U1 0 U2 1 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 EI 1543-5474 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2011 VL 8 SU 1 BP S145 EP S147 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 707KZ UT WOS:000286286600021 PM 21350257 ER PT J AU Censor, N Cohen, LG AF Censor, Nitzan Cohen, Leonardo G. TI Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID THETA-BURST STIMULATION; DORSOLATERAL PREFRONTAL CORTEX; FAST FINGER MOVEMENTS; CHRONIC STROKE; TIME-COURSE; PROCEDURAL KNOWLEDGE; CORTICAL STIMULATION; INTERMANUAL TRANSFER; HEALTHY-SUBJECTS; ISCHEMIC-STROKE AB In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications. C1 [Cohen, Leonardo G.] NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. [Censor, Nitzan; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Cohen, Leonardo G.] NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), NINDS, NIH, Human Cort Physiol Sect, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov NR 89 TC 30 Z9 30 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN PY 2011 VL 589 IS 1 BP 21 EP 28 DI 10.1113/jphysiol.2010.198077 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 700RB UT WOS:000285760900005 PM 21041531 ER PT J AU Boja, E Hiltke, T Rivers, R Kinsinger, C Rahbar, A Mesri, M Rodriguez, H AF Boja, Emily Hiltke, Tara Rivers, Robert Kinsinger, Christopher Rahbar, Amir Mesri, Mehdi Rodriguez, Henry TI Evolution of Clinical Proteomics and its Role in Medicine SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE biomarker; clinical proteomics; protein quantitation; post-translational modifications; multiple reaction monitoring mass spectrometry; enzyme-linked immunosorbent assay; immunohistochemistry; flow cytometry; nanotechnology; verification; qualification; genomics; The Cancer Genome Atlas ID TANDEM MASS-SPECTROMETRY; CODED AFFINITY TAGS; ISOBARIC TAGGING REAGENTS; COMPLEX PROTEIN MIXTURES; LABEL-FREE; QUANTITATIVE PROTEOMICS; BIOMARKER DISCOVERY; ABSOLUTE QUANTIFICATION; 2-DIMENSIONAL ELECTROPHORESIS; PEPTIDE IDENTIFICATION AB Significant progress has been made in characterizing and sequencing genomic alterations of biospecimens from several types of cancer. Understanding the functional changes in the human proteome that arise from the genomic alterations or other factors is the next logical step in the development of high-value protein biomarkers that can be transitioned to clinical studies for biomarker qualification. Linking advances in genomic analysis to proteomic analysis will provide a pathway for qualified biomarkers which can drive the rational development of new diagnostics and therapies. The availability of these multidimensional data to the scientific community sets the stage for the development of new molecularly targeted cancer interventions. C1 [Boja, Emily; Hiltke, Tara; Rivers, Robert; Kinsinger, Christopher; Rahbar, Amir; Mesri, Mehdi; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA. RP Rodriguez, H (reprint author), NCI, Off Canc Clin Prote Res, Ctr Strateg Sci Initiat, NIH, 31 Ctr Dr,MSC 2580, Bethesda, MD 20892 USA. EM rodriguezh@mail.nih.gov NR 142 TC 31 Z9 31 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2011 VL 10 IS 1 BP 66 EP 84 DI 10.1021/pr100532g PG 19 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 701IQ UT WOS:000285812000009 PM 20715861 ER PT J AU Seliger, B Jasinski, S Dressler, SP Marincola, FM Recktenwald, CV Wang, E Lichtenfels, R AF Seliger, Barbara Jasinski, Simon Dressler, Sven P. Marincola, Francesco M. Recktenwald, Christian V. Wang, Ena Lichtenfels, Rudolf TI Linkage of microRNA and Proteome-Based Profiling Data Sets: A Perspective for the Priorization of Candidate Biomarkers in Renal Cell Carcinoma? SO JOURNAL OF PROTEOME RESEARCH LA English DT Editorial Material DE RCC; miR; proteomics; biomarker ID COMPARATIVE GENOMIC HYBRIDIZATION; GENE-EXPRESSION; TARGET PREDICTION; KIDNEY CANCER; THERAPEUTIC TARGETS; CLINICAL-PRACTICE; IDENTIFICATION; MARKERS; CLASSIFICATION; PROTEINS AB Despite recent advances in the understanding of the biology of renal cell carcinoma (RCC) and the implementation of novel targeted therapies, the overall 5 years' survival rate for RCC patients remains disappointing. Late presentation, tumor heterogeneity and in particular the lack of molecular biomarkers for early detection and classification represent major obstacles. Global, untargeted comparative analysis of RCC vs tumor adjacent renal epithelium (NN) samples by high throughput analyses both at the transcriptome and proteome level have identified signatures, which might further clarify the molecular differences of RCC subtypes and might allow the identification of suitable therapeutic targets and diagnostic/prognostic biomarkers, but none thereof has yet been implemented in routine clinical use. The increasing knowledge regarding the functional role of noncoding microRNA (miR) in physiological, developmental, and pathophysiological processes by shaping the protein expression profile might provide an important link to improve the definition of disease-relevant regulatory networks. Taking into account that miR profiling of RCC and NN provides robust signatures discriminating between malignant and normal tissues, the concept of evaluating and scoring miR/protein pairs might represent a strategy for the selection and prioritization of potential biomarkers and their translation into practical use. C1 [Seliger, Barbara; Jasinski, Simon; Dressler, Sven P.; Recktenwald, Christian V.; Lichtenfels, Rudolf] Univ Halle Wittenberg, Inst Med Immunol, D-06112 Halle, Saale, Germany. [Marincola, Francesco M.; Wang, Ena] NIH, Ctr Clin, Dept Transfus Med, Immunogenet Lab, Bethesda, MD 20892 USA. RP Seliger, B (reprint author), Univ Halle Wittenberg, Inst Med Immunol, Magdeburger Str 2, D-06112 Halle, Saale, Germany. EM Barbara.Seliger@medizin.uni-halle.de FU Intramural NIH HHS [ZIA CL002118-03] NR 103 TC 4 Z9 6 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2011 VL 10 IS 1 BP 191 EP 199 DI 10.1021/pr1011137 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 701IQ UT WOS:000285812000023 PM 21142213 ER PT J AU Parry, C Morningstar, E Kendall, J Coleman, EA AF Parry, Carla Morningstar, Elizabeth Kendall, Jeffery Coleman, Eric A. TI Working Without a Net: Leukemia and Lymphoma Survivors' Perspectives on Care Delivery at End-of-Treatment and Beyond SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE care transitions; reentry; survivorship; psycho-oncology; care coordination; health services; oncology health services research ID BREAST-CANCER; TRANSITIONS MEASURE; QUALITY; INTERVENTION; PATIENT; TRIAL; LIFE AB This study explored survivors' perspectives on care delivery and supportive care needs during reentry. Fifty-one individual interviews were conducted with adult leukemia and lymphoma survivors, 3 to 48 months from treatment cessation. Survivors reported poor continuity of care across the patient-survivor transition, difficulty finding appropriate information/services, lack of preparation, lack of support for survivorship issues, and inadequate or poorly timed follow-up as factors contributing to adjustment difficulties at end of treatment and beyond. Improved care coordination is needed after active treatment, including use of an exit interview and delivery of services that are more congruent and better timed to meet ongoing and emergent survivorship needs. C1 [Parry, Carla; Coleman, Eric A.] Univ Colorado Denver, Sch Med, Div Hlth Care Policy & Res, Aurora, CO USA. [Morningstar, Elizabeth] Univ Colorado, Dept Sociol, Boulder, CO 80309 USA. [Kendall, Jeffery] Exempla St Joseph Hosp, Denver, CO USA. RP Parry, C (reprint author), NCI, Off Canc Survivorship, 6116 Execut Blvd,Suite 404, Bethesda, MD 20892 USA. EM Carla.Parry@ucdenver.edu FU NCI NIH HHS [5K07CA108565-02] NR 23 TC 11 Z9 11 U1 2 U2 5 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2011 VL 29 IS 2 BP 175 EP 198 AR PII 934220487 DI 10.1080/07347332.2010.548444 PG 24 WC Psychology, Social SC Psychology GA 733JW UT WOS:000288260000005 PM 21391070 ER PT J AU Peng, QY Park, HS Shah, P Wilson, N Ren, YP Wu, YN Liu, J Gaebler-Spira, DJ Zhang, LQ AF Peng, Qiyu Park, Hyung-Soon Shah, Parag Wilson, Nicole Ren, Yupeng Wu, Yi-Ning Liu, Jie Gaebler-Spira, Deborah J. Zhang, Li-Qun TI Quantitative evaluations of ankle spasticity and stiffness in neurological disorders using manual spasticity evaluator SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE catch angle; cerebral palsy; contracture; manual spasticity evaluator; neurological disorders; quantitative measurement; range of motion; spasticity; Tardieu scale; velocity ID MODIFIED ASHWORTH SCALE; MODIFIED TARDIEU SCALE; CEREBRAL-PALSY; BRAIN-INJURY; INTERRATER RELIABILITY; MUSCLE SPASTICITY; CHILDREN; MANAGEMENT; VELOCITY; SYSTEM AB Spasticity and contracture are major sources of disability in people with neurological impairments that have been evaluated using various instruments: the Modified Ashworth Scale, tendon reflex scale, pendulum test, mechanical perturbations, and passive joint range of motion (ROM). These measures generally are either convenient to use in clinics but not quantitative or they are quantitative but difficult to use conveniently in clinics. We have developed a manual spasticity evaluator (MSE) to evaluate spasticity/contracture quantitatively and conveniently, with ankle ROM and stiffness measured at a controlled low velocity and joint resistance and Tardieu catch angle measured at several higher velocities. We found that the Tardieu catch angle was linearly related to the velocity, indicating that increased resistance at higher velocities was felt at further stiffer positions and, thus, that the velocity dependence of spasticity may also be position-dependent. This finding indicates the need to control velocity in spasticity evaluation, which is achieved with the MSE. Quantitative measurements of spasticity, stiffness, and ROM can lead to more accurate characterizations of pathological conditions and outcome evaluations of interventions, potentially contributing to better healthcare services for patients with neurological disorders such as cerebral palsy, spinal cord injury, traumatic brain injury, and stroke. C1 [Peng, Qiyu; Park, Hyung-Soon; Shah, Parag; Wilson, Nicole; Ren, Yupeng; Wu, Yi-Ning; Liu, Jie; Gaebler-Spira, Deborah J.; Zhang, Li-Qun] Rehabil Inst Chicago, Chicago, IL 60611 USA. [Park, Hyung-Soon; Gaebler-Spira, Deborah J.; Zhang, Li-Qun] Northwestern Univ, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. [Park, Hyung-Soon] NIH, Clin Res Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. [Liu, Jie; Zhang, Li-Qun] Northwestern Univ, Dept Biomed Engn, Chicago, IL 60611 USA. RP Zhang, LQ (reprint author), Rehabil Inst Chicago, 345 E Super St,Suite 1406, Chicago, IL 60611 USA. EM l-zhang@northwestern.edu RI Park, Hyung-Soon/B-3334-2010; peng, qiyu/G-1586-2013; Wilson, Nicole/C-4049-2008 OI Park, Hyung-Soon/0000-0003-4274-7420; Wilson, Nicole/0000-0002-0844-1885 FU National Institutes of Health [R01-HD044295]; National Institute on Disability and Rehabilitation Research [H133S080074]; National Science Foundation [CBET-0854498, IIP-0750515] FX This material was based on work supported with resources from the National Institutes of Health (grant R01-HD044295), National Institute on Disability and Rehabilitation Research (grant H133S080074), and National Science Foundation (grants CBET-0854498 and IIP-0750515). NR 26 TC 12 Z9 13 U1 2 U2 11 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2011 VL 48 IS 4 BP 473 EP 481 DI 10.1682/JRRD.2010.04.0053 PG 9 WC Rehabilitation SC Rehabilitation GA 774GB UT WOS:000291372200013 PM 21674395 ER PT J AU Miller, B Esposito, L McCardle, P AF Miller, Brett Esposito, Layla McCardle, Peggy TI A Public Health Approach to Improving the Lives of Adult Learners: Introduction to the Special Issue on Adult Literacy Interventions SO JOURNAL OF RESEARCH ON EDUCATIONAL EFFECTIVENESS LA English DT Editorial Material DE Adult literacy; adult basic education; intervention; public health; education AB Addressing the literacy needs of adult basic and secondary education learners must form a core part of a broader public health effort to increase educational and health outcomes for these individuals and their families. Adult learners constitute a significant proportion of the overall adult U. S. population and a proportion that impacts, directly and indirectly, on the physical and economic health of millions of families and society writ large. Enhancing the literacy skills of low-literate adults has proven difficult, hampered by the relative dearth of research data on struggling adult learners and effective intervention approaches, the contextual challenges of delivering intensive interventions, limited personal and systemic resources, and competing demands on learners' time. We propose a systems-level view of adult low literacy as one that holds promise and provides a basic framework for providing coordinated, comprehensive, and integrated services but that requires additional research to support. Informed and coordinated efforts with the prekindergarten to 12th-grade education system and health and labor services sectors is needed if we are to improve the lives of these adults and their families. C1 [Miller, Brett; Esposito, Layla; McCardle, Peggy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Miller, B (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Suite 4B05,MSC 7510, Bethesda, MD 20892 USA. EM millerbre@mail.nih.gov NR 49 TC 4 Z9 4 U1 1 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1934-5747 J9 J RES EDUC EFF JI J. Res. Educ. Eff. PY 2011 VL 4 IS 2 SI SI BP 87 EP 100 DI 10.1080/19345747.2011.555287 PG 14 WC Education & Educational Research SC Education & Educational Research GA V29QJ UT WOS:000208762600001 ER PT J AU Assassi, S Reveille, JD Arnett, FC Weisman, MH Ward, MM Agarwal, SK Gourh, P Bhula, J Sharif, R Sampat, K Mayes, MD Tan, FK AF Assassi, Shervin Reveille, John D. Arnett, Frank C. Weisman, Michael H. Ward, Michael M. Agarwal, Sandeep K. Gourh, Pravitt Bhula, Jiten Sharif, Roozbeh Sampat, Keeran Mayes, Maureen D. Tan, Filemon K. TI Whole-blood Gene Expression Profiling in Ankylosing Spondylitis Shows Upregulation of Toll-like Receptor 4 and 5 SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ANKYLOSING SPONDYLITIS; TOLL-LIKE RECEPTORS; IMMUNE SYSTEM; AUTOIMMUNITY; BACTERIA; GENE EXPRESSION PROFILING ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; YERSINIA-ENTEROCOLITICA; BACTERIAL FLAGELLIN; CROHNS-DISEASE; TOLL-LIKE-RECEPTOR-4; SPONDYLOARTHROPATHY; MACROPHAGES; GUT; CELLS; SPONDYLARTHRITIS AB Objective. To identify differentially expressed genes in peripheral blood cells (PBC) of patients with ankylosing spondylitis (AS) relative to healthy controls and controls with systemic inflammation. Methods. We investigated PBC samples of 16 patients with AS and 14 matched controls, in addition to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) samples utilizing Illumina Human Ref-8 Bead Chips. Candidate genes were confirmed using quantitative PCR. Subsequently, these genes were also validated in a separate sample of 27 patients with AS [before and after anti-tumor necrosis factor (anti-TNF) treatment] and 27 matched controls. Results. We identified 83 differentially expressed transcripts between AS patients and controls. This gene list was filtered through the lists of differentially expressed transcripts in SLE and SSc, which resulted in identification of 52 uniquely dysregulated transcripts in AS. Many of the differentially expressed genes belonged to Toll-like receptor (TLR) and related pathways. TLR4 and TLR5 were the only dysregulated TLR subtypes among AS patients. We confirmed the overexpression of TLR4 and TLR5 in AS patients in comparison to controls (p = 0.012 and p = 0.006, respectively) and SLE (p = 0.002, p = 0.008) using quantitative PCR in the same sample. Similarly, TLR4 (p = 0.007) and TLR5 (p = 0.012) were significantly upreadated among the AS patients before anti-TNF treatment in the confirmatory sample. TLR4 (p = 0.002) and TLR5 (p = 0.025) decreased significantly after anti-TNF treatment. Conclusion. PBC gene expression profiling in AS shows an upregulation of TLR4 and TLR5. This supports the importance of TLR subtypes in the pathogenesis of AS that are responsible for the immune response to Gram-negative bacteria. (First Release Oct 15 2010; J Rheumatol 2011; 38:87-98; doi:10.3899/jrheum.100469) C1 [Assassi, Shervin; Reveille, John D.; Arnett, Frank C.; Agarwal, Sandeep K.; Gourh, Pravitt; Bhula, Jiten; Sharif, Roozbeh; Sampat, Keeran; Mayes, Maureen D.; Tan, Filemon K.] Univ Texas Hlth Sci Ctr Houston, Div Rheumatol & Immunogenet, Houston, TX USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA. [Ward, Michael M.] NIAMS, NIH, Bethesda, MD USA. RP Assassi, S (reprint author), Univ Texas Houston, Div Rheumatol, Dept Med, 6431 Fannin,MSB 5-270, Houston, TX 77030 USA. EM shervin.assassi@uth.tmc.edu FU American College of Rheumatology [NIH-KL2RR024149-04]; NIH/NIAMS [P01-AR-052915-01]; NIH/CORT [P50AR054144]; NIH/NCRR [ULI-RR024148] FX Supported by American College of Rheumatology Clinical Investigator Fellowship Award and NIH-KL2RR024149-04 (Dr. Assassi); NIH/NIAMS P01-AR-052915-01 (Dr. Reveille, Dr. Weisman); NIH/CORT P50AR054144 (Dr. Arnett, Dr. Mayes); the Intramural Research Program, NIAMS/NIH (Dr. Ward); and NIH/NCRR Clinical and Translational Sciences Award (CTSA), ULI-RR024148 NR 37 TC 24 Z9 26 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2011 VL 38 IS 1 BP 87 EP 98 DI 10.3899/jrheum.100469 PG 12 WC Rheumatology SC Rheumatology GA 709MZ UT WOS:000286446100015 PM 20952467 ER PT J AU Mealing, NM Bowles, HR Merom, D Bauman, A AF Mealing, Nicole M. Bowles, Heather R. Merom, Dafna Bauman, Adrian TI Impact of scoring algorithm on physical activity prevalence estimates in Australian adults SO JOURNAL OF SCIENCE AND MEDICINE IN SPORT LA English DT Article DE Surveillance; Exercise; Guidelines; Scoring methods ID PUBLIC-HEALTH; SELF-REPORT; RISK; RECOMMENDATIONS; UPDATE AB Public health recommendations for physical activity are operationalised by defining thresholds for frequency (sessions/week), duration (min/week), or volume (MET-min/week). This study compared estimates of meeting physical activity recommendations when scoring algorithms varied in specifications for frequency and duration but were comparable in volume. Data were obtained from 13,105 Australian adult respondents to the 2006 Exercise, Recreation and Sport Survey (ERASS). Prevalence estimates were calculated using algorithms defined by (i) frequency only (>= 5 sessions/week); (ii) duration only (>= 150 min/week); (iii) duration only when minutes of vigorous activity were weighted by 2 (>= 150 weighted-min/week); (iv) frequency and duration (>= 5 sessions/week, >= 150 min/week); (v) volume only (>= 600 MET-min/week); and (vi) volume and frequency (>= 600 MET-min/week, >= 5 sessions/week). The proportion of adults who met recommendations operationalised without a frequency requirement was twice the proportions obtained for algorithms with frequency requirements. Volume or duration-based algorithms yielded higher estimates for men than women, and for the younger age groups (<35 years) than the older groups, with the opposite observation for frequency-based algorithms. Consistent for all algorithms, people classified at the highest educational attainment had the highest prevalence of meeting recommendations. Agreement in achieving 600 MET-min/week when activities were categorised using activity-specific MET values versus median MET values was 98.3%. Prevalence rates based on 600 MET-min/week were similar to 150 weighted-min/week. In conclusion, varying frequency and duration requirements of scoring algorithms can yield different population estimates and patterns by population subgroup of physical activity for a health benefit. (C) 2010 Sports Medicine Australia. Published by All rights reserved. C1 [Mealing, Nicole M.; Bowles, Heather R.; Merom, Dafna; Bauman, Adrian] Univ Sydney, CPAH Prevent Res Collaborat, Sydney, NSW 2006, Australia. [Bowles, Heather R.] NCI, Bethesda, MD 20892 USA. RP Mealing, NM (reprint author), Univ Sydney, CPAH Prevent Res Collaborat, Sydney, NSW 2006, Australia. EM nmea7054@uni.sydney.edu.au NR 18 TC 6 Z9 6 U1 0 U2 0 PU SPORTS MEDICINE AUSTRALIA PI MITCHELL PA 3-5 CHENEY PL, PO BOX 78, MITCHELL, ACT 2911, AUSTRALIA SN 1440-2440 J9 J SCI MED SPORT JI J. Sci. Med. Sport PD JAN PY 2011 VL 14 IS 1 BP 27 EP 32 DI 10.1016/j.jsams.2010.05.003 PG 6 WC Sport Sciences SC Sport Sciences GA 715BA UT WOS:000286854200007 PM 20594908 ER PT J AU Musicki, B Sezen, S Liu, T Chen, H Hsu, L Bivalacqua, T Burnett, A AF Musicki, B. Sezen, S. Liu, T. Chen, H. Hsu, L. Bivalacqua, T. Burnett, A. TI PRIMARY TESTICULAR DYSFUNCTION IN THE TRANSGENIC SICKLE CELL MOUSE-A ROLE FOR OXIDATIVE STRESS? SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [Musicki, B.; Sezen, S.; Liu, T.; Bivalacqua, T.; Burnett, A.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Chen, H.] Johns Hopkins Univ, Baltimore, MD USA. [Hsu, L.] NIH, Bethesda, MD 20892 USA. [Hsu, L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD JAN PY 2011 VL 8 SU 1 BP 13 EP 13 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 702WL UT WOS:000285926500033 ER PT J AU Goldsbury, C Baxa, U Simon, MN Steven, AC Engel, A Wall, JS Aebi, U Muller, SA AF Goldsbury, Claire Baxa, Ulrich Simon, Martha N. Steven, Alasdair C. Engel, Andreas Wall, Joseph S. Aebi, Ueli Mueller, Shirley A. TI Amyloid structure and assembly: Insights from scanning transmission electron microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Review DE Amyloid; Mass measurement; Fibril; Filament; Oligomer; Protein aggregation; Electron microscopy; Scanning transmission electron microscopy; STEM; Alzheimer Disease; Type 2 Diabetes Mellitus; Prion; Scrapie; Yeast; Fungi ID PAIRED HELICAL FILAMENTS; BETA-SHEET STRUCTURE; NUCLEAR-MAGNETIC-RESONANCE; ATOMIC-FORCE MICROSCOPY; URE2P PRION FILAMENTS; NEURONAL CELL-DEATH; SOLID-STATE NMR; HET-S PRION; IN-VITRO; A-BETA AB Amyloid fibrils are filamentous protein aggregates implicated in several common diseases such as Alzheimer's disease and type II diabetes. Similar structures are also the molecular principle of the infectious spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans, scrapie in sheep, and of the so-called yeast prions, inherited non-chromosomal elements found in yeast and fungi. Scanning transmission electron microscopy (STEM) is often used to delineate the assembly mechanism and structural properties of amyloid aggregates. In this review we consider specifically contributions and limitations of STEM for the investigation of amyloid assembly pathways, fibril polymorphisms and structural models of amyloid fibrils. This type of microscopy provides the only method to directly measure the mass-per-length (MPL) of individual filaments. Made on both in vitro assembled and ex vivo samples, STEM mass measurements have illuminated the hierarchical relationships between amyloid fibrils and revealed that polymorphic fibrils and various globular oligomers can assemble simultaneously from a single polypeptide. The MPLs also impose strong constraints on possible packing schemes, assisting in molecular model building when combined with high-resolution methods like solid-state nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR). (C) 2010 Elsevier Inc. All rights reserved. C1 [Simon, Martha N.; Wall, Joseph S.] Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. [Goldsbury, Claire] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. [Baxa, Ulrich; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Engel, Andreas; Mueller, Shirley A.] Univ Basel, Ctr Cellular Imaging & Nanoanalyt, Biozentrum, CH-4058 Basel, Switzerland. [Engel, Andreas; Aebi, Ueli; Mueller, Shirley A.] Univ Basel, ME Muller Inst Struct Biol, Biozentrum, CH-4056 Basel, Switzerland. RP Wall, JS (reprint author), Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. EM wall@bnl.gov; shirley.mueller@unibas.ch FU Swiss National Foundation [3100A0-108299]; Maurice E Muller Foundation of Switzerland; NIAMS, National Institutes of Health; USDOE-OHER (Department of Energy, Office of Health and Environmental Research) FX We thank all current and past operators of the Basel STEM for their contributions to the cited work and Robert Haring, Robert Wyss and Roland Burki for maintenance of the instrument and its computer system. We thank Robert Tycko, Beat Meier and David Eisenberg for data and images adapted in Figs. 2 and 4. The Basel STEM has been continuously supported by Swiss National Foundation grants (present Grant: 3100A0-108299 to A.E.) and by the Maurice E Muller Foundation of Switzerland. This work was supported in part by the Intramural Research Program of NIAMS, National Institutes of Health. The BNL STEM is supported by USDOE-OHER (Department of Energy, Office of Health and Environmental Research). NR 98 TC 44 Z9 45 U1 4 U2 39 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN PY 2011 VL 173 IS 1 BP 1 EP 13 DI 10.1016/j.jsb.2010.09.018 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 705JB UT WOS:000286123600001 PM 20868754 ER PT J AU Wallace, JM Orr, BG Marini, JC Holl, MMB AF Wallace, Joseph M. Orr, Bradford G. Marini, Joan C. Holl, Mark M. Banaszak TI Nanoscale morphology of Type I collagen is altered in the Brtl mouse model of Osteogenesis Imperfecta SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE AFM; Ultrastructure; Nanoscale; 2D FFT; Genotype/phenotype ID MORPHOMETRIC-ANALYSIS; MURINE MODEL; BONE; FIBRILS; MINERALIZATION; DISEASE; SUBSTITUTION; DEFORMATION; MECHANISMS; EXPRESSION AB Bone has a complex hierarchical structure that has evolved to serve structural and metabolic roles in the body. Due to the complexity of bone structure and the number of diseases which affect the ultrastructural constituents of bone, it is important to develop quantitative methods to assess bone nanoscale properties. Autosomal dominant Osteogenesis Imperfecta results predominantly from glycine substitutions (80%) and splice site mutations (20%) in the genes encoding the alpha 1 or alpha 2 chains of Type I collagen. Genotype-phenotype correlations using over 830 collagen mutations have revealed that lethal mutations are located in regions crucial for collagen-ligand binding in the matrix. However, few of these correlations have been extended to collagen structure in bone. Here, an atomic force microscopy-based approach was used to image and quantitatively analyze the D-periodic spacing of Type I collagen fibrils in femora from heterozygous (Brtl/+) mice (alpha 1(1)G349C), compared to wild type (WT) littermates. This disease system has a well-defined change in the coll alpha 1 allele, leading to a well characterized alteration in collagen protein structure, which are directly related to altered Type I collagen nanoscale morphology, as measured by the D-periodic spacing. In Brtl/+ bone, the D-periodic spacing shows significantly greater variability on average and along the length of the bone compared to WT, although the average spacing was unchanged. Brtl/+ bone also had a significant difference in the population distribution of collagen D-period spacings. These changes may be due to the mutant collagen structure, or to the heterogeneity of collagen monomers in the Brtl/+ matrix. These observations at the nanoscale level provide insight into the structural basis for changes present in bone composition, geometry and mechanical integrity in Brtl/+ bones. Further studies are necessary to link these morphological observations to nanoscale mechanical integrity. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wallace, Joseph M.; Holl, Mark M. Banaszak] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Wallace, Joseph M.; Orr, Bradford G.; Holl, Mark M. Banaszak] Univ Michigan, Michigan Nanotechnol Inst Med & Biol Sci, Ann Arbor, MI 48109 USA. [Orr, Bradford G.] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA. [Orr, Bradford G.; Holl, Mark M. Banaszak] Univ Michigan, Program Appl Phys, Ann Arbor, MI 48109 USA. [Holl, Mark M. Banaszak] Univ Michigan, Program Biophys, Ann Arbor, MI 48109 USA. [Holl, Mark M. Banaszak] Univ Michigan, Program Macromol Sci & Engn, Ann Arbor, MI 48109 USA. [Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Wallace, JM (reprint author), Univ Michigan, Dept Chem, 930 N Univ Ave, Ann Arbor, MI 48109 USA. EM jmwallac@umich.edu; orr@umich.edu; oidoc@helix.nih.gov; mbanasza@umich.edu RI Wallace, Joseph/G-7906-2012; Banaszak Holl, Mark/D-2030-2013 OI Banaszak Holl, Mark/0000-0001-7759-7456 FU National Institute of Dental and Craniofacial Research (National Institutes of Health) [1F32DE018840-01 A1]; NICHD FX This work was partially supported by the National Institute of Dental and Craniofacial Research (National Institutes of Health) through a Ruth L Kirschstein National Service Award (Grant number 1F32DE018840-01 A1). JCM is supported by NICHD Intramural Funding. The authors thank Wayne Cabral for generation of Brtl/WT mice used in these experiments. NR 34 TC 40 Z9 40 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 1047-8477 EI 1095-8657 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN PY 2011 VL 173 IS 1 BP 146 EP 152 DI 10.1016/j.jsb.2010.08.003 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 705JB UT WOS:000286123600016 PM 20696252 ER PT J AU Rutter, M AF Rutter, Michael TI Integrating Science and Clinical Practice SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID PSYCHOPATHOLOGY; RISK C1 [Rutter, Michael] Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Rutter, Michael] MRC, Child Psychiat Unit, London W1N 4AL, England. [Rutter, Michael] Natl Inst Mental Hlth Intramural Program, Bethesda, MD USA. [Rutter, Michael] MRC Social, Genet & Dev Res Ctr, London, England. [Rutter, Michael] Maudsley Hosp & Inst Psychiat, Clin Unit, London, England. RP Rutter, M (reprint author), Kings Coll London, Inst Psychiat, Genet & Dev Psychiat Ctr, PO 80,Crespigny Pk,Denmark Hill, London SE5 8AF, England. EM camilla.azis@kcl.ac.uk RI Rutter, Michael/C-8570-2013 NR 8 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2011 VL 50 IS 1 BP 3 EP 5 DI 10.1016/i.jaac.2010.06.005 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 700WX UT WOS:000285776100001 PM 21156264 ER PT J AU Merikangas, KR He, JP Burstein, M Swendsen, J Avenevoli, S Case, B Georgiades, K Heaton, L Swanson, S Olfson, M AF Merikangas, Kathleen Ries He, Jian-ping Burstein, Marcy Swendsen, Joel Avenevoli, Shelli Case, Brady Georgiades, Katholiki Heaton, Leanne Swanson, Sonja Olfson, Mark TI Service Utilization for Lifetime Mental Disorders in U.S. Adolescents: Results of the National Comorbidity Survey-Adolescent Supplement (NCS-A) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE epidemiology; adolescents; mental disorders; treatment; services ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; HEALTH-SERVICES; SURVEY REPLICATION; UNITED-STATES; DEPRESSION TREATMENT; AFRICAN-AMERICAN; US CHILDREN; UNMET NEED; ADHD AB Objective: Mental health policy for youth has been constrained by a paucity of nationally representative data concerning patterns and correlates of mental health service utilization in this segment of the population. The objectives of this investigation were to examine the rates and sociodemographic correlates of lifetime mental health service use by severity, type, and number of DSM-IV disorders in the National Comorbidity Survey-Adolescent Supplement. Method: Face-to-face survey of mental disorders from 2002 to 2004 using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview in a nationally representative sample of 6,483 adolescents 13 to 18 years old for whom information on service use was available from an adolescent and a parent report. Total and sector-specific mental health service use was also assessed. Results: Approximately one third of adolescents with mental disorders received services for their illness (36.2%). Although disorder severity was significantly associated with an increased likelihood of receiving treatment, half of adolescents with severely impairing mental disorders had never received mental health treatment for their symptoms. Service rates were highest in those with attention-deficit/hyperactivity disorder (59.8%) and behavior disorders (45.4%), but fewer than one in five affected adolescents received services for anxiety, eating, or substance use disorders. Comorbidity and severe impairment were strongly associated with service utilization, particularly in youth with behavior disorders. Hispanic and non-Hispanic Black adolescents were less likely than their White counterparts to receive services for mood and anxiety disorders, even when such disorders were associated with severe impairment. Conclusions: Despite advances in public awareness of mental disorders in youth, a substantial proportion of young people with severe mental disorders have never received specialty mental health care. Marked racial disparities in lifetime rates of mental health treatment highlight the urgent need to identify and combat barriers to the recognition and treatment of these conditions. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(1):32-45. C1 [Merikangas, Kathleen Ries; He, Jian-ping; Burstein, Marcy; Heaton, Leanne] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Swendsen, Joel] CNRS, Natl Ctr Sci Res, Bordeaux, France. [Avenevoli, Shelli] NIMH, Div Dev Translat Res Branch, Bethesda, MD 20892 USA. [Case, Brady] NYU, Sch Med, New York, NY 10003 USA. [Georgiades, Katholiki] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Olfson, Mark] Columbia Univ, Med Ctr, New York, NY 10027 USA. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bldg 35,Room 1A201,35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM kathleen.merikangas@nih.gov RI Case, Brady/M-1879-2015 OI Case, Brady/0000-0001-9512-0416 FU National Institute of Mental Health; National Institute of Mental Health [U01-MH602201]; National Institute of Drug Abuse [R01 DA016558]; Robert Wood Johnson Foundation [10447081]; John W. Alden Trust; Eli Lilly and Co.; Bristol-Myers Squibb FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or U.S. Government.; The National Comorbidity Survey Adolescent Supplement (NCS-A) and the larger program of related National Comorbidity Surveys are supported by the National Institute of Mental Health (U01-MH602201 and the National Institute of Drug Abuse (R01 DA016558) with supplemental support from Substance Abuse and Mental Health Services Administration, the Robert Wood Johnson Foundation 10447081, and the John W. Alden Trust. The NCS-A was carried out in conjunction with the World Health Organization World Mental Health Survey Initiative.; Dr. Olfson has received research support to Columbia University from Eli Lilly and Co. and Bristol-Myers Squibb. Drs. Merikangas, Burstein, Swendsen, Avenevoli, Case, Georgiades, and Heaton, and Ms. He, and Ms. Swanson report no biomedical financial interests or potential conflicts of interest. NR 58 TC 264 Z9 264 U1 15 U2 61 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2011 VL 50 IS 1 BP 32 EP 45 DI 10.1016/j.jaac.2010.10.006 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 700WX UT WOS:000285776100005 PM 21156268 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB This document is a summary report of the Guidelines for the Diagnosis and Management of Food Allergy in the United States. The full guidelines can be found online at http://www.jacionline.org C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Rheumatol Immunol & Allergy, Cambridge, MA 02138 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Emergency Med, Dept Med,Div Rheumatol Allergy & Immunol, Cambridge, MA 02138 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Pulm & Crit Med Div, Boston, MA 02115 USA. [Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45221 USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Dept Pediat, Div Allergy & Immunol, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton SO9 5NH, Hants, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Baton Rouge, LA 70803 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Furuta, Glenn T.] Univ Colorado, Dept Pediat, Denver Sch Med, Aurora, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Lieberman, Phil] Univ Tennessee, Coll Med, Div Allergy & Immunol, Dept Med, Knoxville, TN 37996 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB R3T 2N2, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB R3T 2N2, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institutes of Health and the National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; variety of government agencies; not-for-profit research foundations; Dey; Novartis; variety of not-for-profit foundations; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; variety of not-for-profit research foundations; AllerGen; Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX J.A. Boyce has served on the Advisory Board of GlaxoSmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S.M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network.She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H.A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R.A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S.H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S.L. Bahna has received funding/grant support from Genentech.; L.A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C.A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G.T. Furuta has served as a consultant and/or speaker to Ception Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J.M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc, Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; M. Kraft has served as a consultant and/or speaker for Astra-Zeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sepracor. She has received funding/grant support from Genentech, GlaxoSmithKline, the National Institutes of Health and Novartis.; L.C. Schneider has served as a consultant/clinical advisor for the Food Allergy Initiative. She has received funding/grant support from a variety of not-for-profit research foundations, as well as Novartis and the National Institutes of Health.; F.E.R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma, and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health Research.; S.J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 0 TC 13 Z9 13 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2011 VL 64 IS 1 BP 175 EP 192 DI 10.1016/j.jaad.2010.11.020 PG 18 WC Dermatology SC Dermatology GA 701XF UT WOS:000285857800021 PM 21167411 ER PT J AU Dores, GM Huycke, MM Devesa, SS AF Dores, Graca M. Huycke, Mark M. Devesa, Susan S. TI Melanoma of the skin and laterality SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Dores, Graca M.; Huycke, Mark M.] Dept Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. [Huycke, Mark M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Dores, Graca M.; Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Dores, GM (reprint author), Dept Vet Affairs Med Ctr, 921 NE 13th St, Oklahoma City, OK 73104 USA. EM doresg@mail.nih.gov FU Intramural NIH HHS [ZIA CP010183-07] NR 4 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2011 VL 64 IS 1 BP 193 EP 195 DI 10.1016/j.jaad.2010.06.062 PG 3 WC Dermatology SC Dermatology GA 701XF UT WOS:000285857800022 PM 21167412 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med,Med Sch, Boston, MA 02115 USA. [Assa'ad, Amal] Univ Cincinnati, Med Ctr, Cincinnati Childrens Hosp, Div Allergy & Immunol, Cincinnati, OH 45267 USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Div Allergy & Immunol, Dept Pediat, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 10 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2011 VL 111 IS 1 BP 17 EP 27 DI 10.1016/j.jada.2010.10.033 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 703CF UT WOS:000285951000004 PM 21185960 ER PT J AU Anderson, AL Harris, TB Tylavsky, FA Perry, SE Houston, DK Hue, TF Strotmeyer, ES Sahyoun, NR AF Anderson, Amy L. Harris, Tamara B. Tylavsky, Frances A. Perry, Sara E. Houston, Denise K. Hue, Trisha F. Strotmeyer, Elsa S. Sahyoun, Nadine R. CA Hlth ABC Study TI Dietary Patterns and Survival of Older Adults SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID LOW VITAMIN-B-12 STATUS; CARDIOVASCULAR EVENTS; PLASMA HOMOCYSTEINE; ALZHEIMERS-DISEASE; 10-YEAR MORTALITY; ELDERLY SUBJECTS; HEART-DISEASE; HALE PROJECT; COHORT; WOMEN AB Background Recent research has linked overall dietary patterns to survival in older adults Objectives The objective of this study was to determine the dietary patterns of a cohort of older adults, and to explore associations of these dietary patterns with survival over a 10-year period A secondary goal was to evaluate participants' quality of life and nutritional status according to their dietary patterns Design The Health, Aging, and Body Composition Study is a prospective cohort study of 3,075 older adults In this study, all cause mortality was assessed from baseline through Year 10 Food intake was estimated with a modified Block food frequency questionnaire, and dietary patterns of 2,582 participants with complete data were derived by cluster analysis Results Six dietary pattern clusters were identified, including a Healthy Foods cluster, characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish, and vegetables Both the High-Fat Dairy Products and Sweets and Desserts clusters had a 1 4 fold higher risk of mortality than the Healthy Foods cluster after adjusting for potential confounders The Healthy Foods cluster also had significantly more years of healthy life and more favorable levels of selected nutritional biomarkers than the other clusters Conclusions A dietary pattern consistent with current guidelines to consume relatively high amounts of vegetables, fruit, whole grains, poultry, fish, and low-fat dairy products may be associated with superior nutritional status, quality of life and survival in older adults J Am Diet Assoc 2011,111 84 91 C1 [Anderson, Amy L.; Sahyoun, Nadine R.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Harris, Tamara B.] NIA, Geriatr Epidemiol Sect, Bethesda, MD 20892 USA. [Tylavsky, Frances A.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Perry, Sara E.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Houston, Denise K.] Wake Forest Univ, Sch Med, Dept Internal Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Hue, Trisha F.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA USA. RP Anderson, AL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. RI Sahyoun, Nadine/G-2608-2011; Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging [N01 AG-6-2101, N01-AG 6-2103, N01-AG-6-2106]; National Institutes of Health, National Institute on Aging FX The Health ABC Study was supported by National Institute on Aging contracts N01 AG-6-2101, N01-AG 6-2103, and N01-AG-6-2106 This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging NR 35 TC 44 Z9 46 U1 1 U2 14 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JAN PY 2011 VL 111 IS 1 BP 84 EP 91 DI 10.1016/j.jada.2010.10.012 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 703CF UT WOS:000285951000013 PM 21185969 ER PT J AU Atkinson, NL Massett, HA Mylks, C McCormack, LA Kish-Doto, J Hesse, BW Wang, MQ AF Atkinson, Nancy L. Massett, Holly A. Mylks, Christy McCormack, Lauren A. Kish-Doto, Julia Hesse, Bradford W. Wang, Min Qi TI Assessing the impact of user-centered research on a clinical trial eHealth tool via counterbalanced research design SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CANCER-PATIENTS; PARTICIPATION; RECRUITMENT; EXPERIENCE; ATTITUDES; BARRIERS; INTERNET AB Objective Informatics applications have the potential to improve participation in clinical trials, but their design must be based on user-centered research. This research used a fully counterbalanced experimental design to investigate the effect of changes made to the original version of a website, http://BreastCancerTrials.org/, and confirm that the revised version addressed and reinforced patients' needs and expectations. Design Participants included women who had received a breast cancer diagnosis within the last 5 years (N=77). They were randomized into two groups: one group used and reviewed the original version first followed by the redesigned version, and the other group used and reviewed them in reverse order. Measurements The study used both quantitative and qualitative measures. During use, participants' click paths and general reactions were observed. After use, participants were asked to answer survey items and open-ended questions to indicate their reactions and which version they preferred and met their needs and expectations better. Results Overall, the revised version of the site was preferred and perceived to be clearer, easier to navigate, more trustworthy and credible, and more private and safe overall. However, users who viewed the original version last had similar attitudes toward both versions. Conclusion By applying research findings to the redesign of a website for clinical trial searching, it was possible to re-engineer the interface to better support patients' decisions to participate in clinical trials. The mechanisms of action in this case appeared to revolve around creating an environment that supported a sense of personal control and decisional autonomy. C1 [Atkinson, Nancy L.; Wang, Min Qi] Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA. [Massett, Holly A.] NCI, Off Market Res & Evaluat, NIH, Rockville, MD USA. [Mylks, Christy] IDox Solut, Bethesda, MD USA. [McCormack, Lauren A.] RTI Int, Res Triangle Pk, NC USA. [Hesse, Bradford W.] US Natl Canc Inst, Hlth Commun & Informat Res Branch, NIH, Rockville, MD USA. RP Atkinson, NL (reprint author), Univ Maryland, Dept Publ & Community Hlth, Suite 2387 Valley Dr, College Pk, MD 20742 USA. EM atkinson@umd.edu OI Hesse, Bradford/0000-0003-1142-1161 FU National Cancer Institute's Office of Market Research and Evaluation; National Cancer Institute, Rockville, MD FX The National Cancer Institute's Office of Market Research and Evaluation funded the study design, collection, management, analysis, and interpretation of the data, and preparation, review, and approval of the manuscript. The systems tested were developed collaboratively by: NCI's Center for Biomedical Informatics and Technology, which manages the cancer Biomedical Informatics Grid (caBIG) initiative; NCI's Office of Communications and Education, which manages NCI's clinical trials database POD; and the University of California, Sari Francisco, Comprehensive Cancer Center and the UCSF Center of Excellence for Breast Cancer Care. We also thank: Dr Gretchen Kimmick, oncologist from Duke University Medical Center, Durham, North Carolina; Ms Regina Heroux, Cancer Outreach Manager, Rex Hospital, Raleigh, North Carolina; and our other collaborators at NCI and RTI who helped with this effort (Farrah Darbouze; Brenda Duggan; Mary Jo Deering, PhD; Katherine Treiman, PhD; Tania Fitzgerald; and Claudia Squire, MS).; National Cancer Institute, NIH6116 Executive Blvd, Suite 400, Rockville, MD 20852. NR 24 TC 5 Z9 5 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JAN PY 2011 VL 18 IS 1 BP 24 EP 31 DI 10.1136/jamia.2010.006122 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 746BZ UT WOS:000289218000005 PM 21169619 ER PT J AU Anderson, S Eldadah, B Halter, JB Hazzard, WR Himmelfarb, J Horne, FM Kimmel, PL Molitoris, BA Murthy, M O'Hare, AM Schmader, KE High, KP AF Anderson, Sharon Eldadah, Basil Halter, Jeffrey B. Hazzard, William R. Himmelfarb, Jonathan Horne, Frances McFarland Kimmel, Paul L. Molitoris, Bruce A. Murthy, Mahadev O'Hare, Ann M. Schmader, Kenneth E. High, Kevin P. TI Acute Kidney Injury in Older Adults SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; PERCUTANEOUS CORONARY INTERVENTION; CRITICALLY-ILL PATIENTS; ISCHEMIA-REPERFUSION INJURY; LONG-TERM MORTALITY; ACUTE LUNG INJURY; QUALITY-OF-LIFE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GELATINASE-ASSOCIATED LIPOCALIN; ACUTE TUBULAR-NECROSIS AB Aging kidneys undergo structural and functional changes that decrease autoregulatory capacity and increase susceptibility to acute injury. Acute kidney injury associates with duration and location of hospitalization, mortality risk, progression to chronic kidney disease, and functional status in daily living. Definition and diagnosis of acute kidney injury are based on changes in creatinine, which is an inadequate marker and might identify patients when it is too late. The incidence of acute kidney injury is rising and increases with advancing age, yet clinical studies have been slow to address geriatric issues or the heterogeneity in etiologies, outcomes, or patient preferences among the elderly. Here we examine some of the current literature, identify knowledge gaps, and suggest potential research questions regarding acute kidney injury in older adults. Answering these questions will facilitate the integration of geriatric issues into future mechanistic and clinical studies that affect management and care of acute kidney injury. C1 [High, Kevin P.] Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Dept Internal Med, Winston Salem, NC 27157 USA. [Anderson, Sharon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Anderson, Sharon] Portland VA Med Ctr, Portland, OR USA. [Eldadah, Basil; Murthy, Mahadev] NIA, Bethesda, MD 20892 USA. [Halter, Jeffrey B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Hazzard, William R.; O'Hare, Ann M.] Univ Washington, Sch Med, Seattle, WA USA. [Hazzard, William R.; Himmelfarb, Jonathan] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Horne, Frances McFarland] Assoc Specialty Prof, Washington, DC USA. [Kimmel, Paul L.] NIDDK, Bethesda, MD USA. [Molitoris, Bruce A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Schmader, Kenneth E.] Duke Univ, Durham, NC USA. [Schmader, Kenneth E.] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. RP High, KP (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Dept Internal Med, 100 Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wfubmc.edu FU Association of Specialty Professors; American Society of Nephrology; American Geriatrics Society; National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases; John A. Hartford Foundation FX For those who attended a workshop on May 10-11, 2010 sponsored by the Association of Specialty Professors, the American Society of Nephrology, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases.; This workshop was supported by a generous grant from the John A. Hartford Foundation to A.S.P. We are grateful to Charles Clayton and Erika Tarver for assistance with organizing the workshop. For a full list of moderators and attendees of the conference, please visit http://www.im.org/CareerDevelopment/ GrantsandScholarships/IGP/Expanding ResearchEfforts/Pages/WorkshoponAcute KidneyInjuryinOlderAdults.aspx. NR 173 TC 54 Z9 59 U1 1 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 28 EP 38 DI 10.1681/ASN.2010090934 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500009 PM 21209252 ER PT J AU Asico, L Zhang, XJ Jiang, JF Cabrera, D Escano, CS Sibley, DR Wang, XY Yang, Y Mannon, R Jones, JE Armando, I Jose, PA AF Asico, Laureano Zhang, Xiaojie Jiang, Jifu Cabrera, David Escano, Crisanto S. Sibley, David R. Wang, Xiaoyan Yang, Yu Mannon, Roslyn Jones, John E. Armando, Ines Jose, Pedro A. TI Lack of Renal Dopamine D-5 Receptors Promotes Hypertension SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PROXIMAL TUBULE CELLS; ANGIOTENSIN-II TYPE-1; SMOOTH-MUSCLE-CELLS; NA+-K+-ATPASE; BLOOD-PRESSURE; DEPENDENT INHIBITION; INTRARENAL DOPAMINE; OXIDATIVE STRESS; GENOME SCAN; RAT AB Disruption of the dopamine D-5 receptor gene in mice increases BP and causes salt sensitivity. To determine the role of renal versus extrarenal D-5 receptors in BP regulation, we performed cross-renal transplantation experiments. BP was similar between wild-type mice and wild-type mice transplanted with wild-type kidneys, indicating that the transplantation procedure did not affect BP. BP was lower among D-5(-/-) mice transplanted with wild-type kidneys than D-5(-/-) kidneys, demonstrating that the renal D-5 receptors are important in BP control. BP was higher in wild-type mice transplanted with D-5(-/-) kidneys than wild-type kidneys but not significantly different from syngenic transplanted D-5(-/-) mice, indicating the importance of the kidney in the development of hypertension. On a high-salt diet, all mice with D-5(-/-) kidneys excreted less sodium than mice with wild-type kidneys. Transplantation of a wild-type kidney into a D-5(-/-) mouse decreased the renal expression of AT(1) receptors and Nox-2. Conversely, transplantation of a D-5(-/-) kidney into a wild-type mouse increased the expression of both, suggesting that both renal and extrarenal factors are important in the regulation of AT(1) receptor and Nox-2 expression. These results highlight the role of renal D-5 receptors in BP homeostasis and the pathogenesis of hypertension. C1 [Asico, Laureano; Escano, Crisanto S.; Wang, Xiaoyan; Yang, Yu; Jones, John E.; Armando, Ines; Jose, Pedro A.] Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA. [Zhang, Xiaojie] NIDDK, Lab Anim Sci, NIH, Bethesda, MD USA. [Jiang, Jifu] Univ Western Ontario, London Hlth Sci Ctr, Robarts Res Inst, London, ON, Canada. [Cabrera, David; Sibley, David R.] Natl Inst Neurol Disorders & Stroke, Mol Neuropharmacol Sect, NIH, Bethesda, MD USA. [Mannon, Roslyn] Univ Alabama, Alabama Transplant Ctr, Birmingham, AL USA. RP Jose, PA (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, 111 Michigan Ave NW, Washington, DC 20010 USA. EM PJose@cnmc.org RI Cabrera, David/I-1013-2014 FU National Institutes of Health [HL068686, HL023081, HL074940, HL092196, DK039308] FX This work was supported in part by grants from the National Institutes of Health (HL068686 HL023081, HL074940, HL092196, and DK039308). NR 62 TC 17 Z9 19 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 82 EP 89 DI 10.1681/ASN.2010050533 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500015 PM 21051739 ER PT J AU Ly, JP Onay, T Sison, K Sivaskandarajah, G Sabbisetti, V Li, LL Bonventre, JV Flenniken, A Paragas, N Barasch, JM Adamson, SL Osborne, L Rossant, J Schnermann, J Quaggin, SE AF Ly, Joseph P. Onay, Tuncer Sison, Karen Sivaskandarajah, Gavasker Sabbisetti, Venkata Li, Lingli Bonventre, Joseph V. Flenniken, Ann Paragas, Neal Barasch, Jon M. Adamson, S. Lee Osborne, Lucy Rossant, Janet Schnermann, Jurgen Quaggin, Susan E. TI The Sweet Pee Model for Sglt2 Mutation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLUCOSE-TOLERANCE; MOUSE MUTAGENESIS; RENAL GLUCOSURIA; MESSENGER-RNA; MICE; DAPAGLIFLOZIN; PHYSIOLOGY; TRANSPORT; GITELMANS; BARTTERS AB Inhibiting renal glucose transport is a potential pharmacologic approach to treat diabetes. The renal tubular sodium-glucose transporter 2 (SGLT2) reabsorbs approximately 90% of the filtered glucose load. An animal model with sglt2 dysfunction could provide information regarding the potential long-term safety and efficacy of SGLT2 inhibitors, which are currently under clinical investigation. Here, we describe Sweet Pee, a mouse model that carries a nonsense mutation in the Slc5a2 gene, which results in the loss of sglt2 protein function. The phenotype of Sweet Pee mutants was remarkably similar to patients with mutations in the Scl5a2 gene. The Sweet Pee mutants had improved glucose tolerance, higher urinary excretion of calcium and magnesium, and growth retardation. Renal physiologic studies demonstrated a prominent distal osmotic diuresis without enhanced natriuresis. Sweet Pee mutants did not exhibit increased KIM-1 or NGAL, markers of acute tubular injury. After induction of diabetes, Sweet Pee mice had better overall glycemic control than wild-type control mice, but had a higher risk for infection and an increased mortality rate (70% in homozygous mutants versus 10% in controls at 20 weeks). In summary, the Sweet Pee model allows study of the long-term benefits and risks associated with inhibition of SGLT2 for the management of diabetes. Our model suggests that inhibiting SGLT2 may improve glucose control but may confer increased risks for infection, malnutrition, volume contraction, and mortality. C1 [Ly, Joseph P.; Onay, Tuncer; Sison, Karen; Sivaskandarajah, Gavasker; Flenniken, Ann; Adamson, S. Lee; Quaggin, Susan E.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3H7, Canada. [Sabbisetti, Venkata; Bonventre, Joseph V.] Brigham & Womens Hosp, Harvard Inst Med, Boston, MA 02115 USA. [Li, Lingli; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA. [Flenniken, Ann; Adamson, S. Lee; Osborne, Lucy; Rossant, Janet] Toronto Ctr Phenogen, Ctr Modeling Human Dis, Toronto, ON, Canada. [Paragas, Neal; Barasch, Jon M.] Columbia Univ, Dept Med, New York, NY USA. [Osborne, Lucy] Univ Toronto, St Michaels Hosp, Dept Med, Toronto, ON M5B 1W8, Canada. [Osborne, Lucy] Univ Toronto, St Michaels Hosp, Dept Mol Genet, Toronto, ON M5B 1W8, Canada. [Quaggin, Susan E.] Univ Toronto, St Michaels Hosp, Div Nephrol, Toronto, ON M5B 1W8, Canada. [Quaggin, Susan E.] Univ Toronto, Dept Med, Univ Hlth Network, Toronto, ON, Canada. [Rossant, Janet] Hosp Sick Children, Dev & Stem Cell Biol Program, Toronto, ON M5G 1X8, Canada. RP Quaggin, SE (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, TCP Bldg,Room 5-1015-2,25 Orde St, Toronto, ON M5T 3H7, Canada. EM quaggin@lunenfeld.ca RI Adamson, S. Lee/E-4581-2013; OI Adamson, S. Lee/0000-0002-7340-3041; Paragas, Neal/0000-0001-6084-8220 FU CIHR [MOP 77756, 62931]; TF [016002]; KFOC; MRC [GSP 36653]; KRESCENT program; Kidney Foundation of Canada FX We thank Jasmine Bahrami and the Drucker Lab for assistance and advice regarding metabolic tests and Dr. Kamel Kamel for critical appraisal and discussion. We gratefully acknowledge the measurement of plasma renin by Yuning Huang and Diane Mizel. This work was funded by CIHR grants MOP 77756, 62931, TF grant 016002, and KFOC grant to S.E.Q., MRC grant GSP 36653 to C.M.H.D. S.E.Q. holds the Gabor-Zellerman Chair in Renal Research, UHN, University of Toronto, and is the recipient of a CRC Canada Research Chair Tier II. J.L. is supported by the KRESCENT program, Kidney Foundation of Canada, and CIHR. S.L.A. holds the Anne and Max Tanenbaum Chair, MSH. NR 34 TC 29 Z9 29 U1 0 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2011 VL 22 IS 1 BP 113 EP 123 DI 10.1681/ASN.2010080888 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 730PN UT WOS:000288046500018 PM 21209254 ER PT J AU Boller, F AF Boller, Francois TI Untitled SO JOURNAL OF THE HISTORY OF THE NEUROSCIENCES LA English DT Letter C1 NIMH, Div Extramural Activ, Bethesda, MD 20892 USA. RP Boller, F (reprint author), NIMH, Div Extramural Activ, Room 6142 MSC 9806,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bollerf@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0964-704X J9 J HIST NEUROSCI JI J. Hist. Neurosci. PY 2011 VL 20 IS 4 BP 379 EP 380 DI 10.1080/0964704X.2011.603637 PG 2 WC History & Philosophy Of Science; Neurosciences SC History & Philosophy of Science; Neurosciences & Neurology GA 885QB UT WOS:000299792900009 PM 22003865 ER PT J AU Beaudoin, DE Longo, N Logan, RA Jones, JP Mitchell, JA AF Beaudoin, Denise E. Longo, Nicola Logan, Robert A. Jones, Jason P. Mitchell, Joyce A. TI Using information prescriptions to refer patients with metabolic conditions to the Genetics Home Reference website SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID INTERNET; PARENTS; EDUCATION; PROVIDE AB Objectives: The objectives of this study were to assess the reactions of adult patients and parents of children with metabolic conditions to receipt of an "information prescription" (IP) to visit Genetics Home Reference (GHR), a National Institutes of Health/National Library of Medicine online resource, and evaluate the perceived utility of information found on the site. Methods: Patients seen at the University of Utah Metabolic Service Clinic were invited to participate in the study and asked to complete an initial survey to gather demographic data and an online survey six weeks later to obtain information about user experience. Results: Fifty-three of 82 individuals completed both surveys, for an overall response rate of 64.6%. Most respondents (88.7%) agreed that receiving the IP was a "good idea," and nearly all used the IP to visit GHR. More than three-quarters (79.6%) agreed that information on GHR supplemented a physician's advice; 60.4% reported an improved understanding of a health condition; and 41.5% either looked for or would consider looking for additional information. Eighty-six percent of respondents were satisfied with the information found on GHR, and 80% would recommend the site. Conclusions: Use of an IP to direct patients to GHR was well received, and retrieved information was perceived as useful in key areas. The high level of satisfaction with GHR argues for expanded use of the IP approach in this patient population. C1 [Beaudoin, Denise E.; Jones, Jason P.; Mitchell, Joyce A.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA. [Longo, Nicola] Univ Utah, Dept Pediat, Div Med Genet, Salt Lake City, UT 84132 USA. [Logan, Robert A.] Natl Lib Med, Bethesda, MD 20894 USA. RP Beaudoin, DE (reprint author), Univ Utah, Dept Biomed Informat, 26 South 2000 East,Hlth Sci Educ Bldg,Suite 5700, Salt Lake City, UT 84112 USA. EM denise.beaudoin@hsc.utah.edu; nicola.longo@hsc.utah.edu; logan@nlm.nih.gov; j.jones@imail.org; joyce.mitchell@hsc.utah.edu FU NLM NIH HHS [N01-LM-6-3504] NR 20 TC 6 Z9 6 U1 0 U2 8 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2011 VL 99 IS 1 BP 70 EP 76 DI 10.3163/1536-5050.99.1.012 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 739FU UT WOS:000288700700012 PM 21243058 ER PT J AU Khan, M Kamal, AK AF Khan, Maria Kamal, Ayeesha Kamran TI What modifiable risk factors lead to strokes in our part of the world? SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION LA English DT Article C1 [Khan, Maria] Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Fogarty Int Ctr, Karachi, Pakistan. Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan. RP Khan, M (reprint author), Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Fogarty Int Ctr, Karachi, Pakistan. NR 1 TC 3 Z9 3 U1 0 U2 0 PU PAKISTAN MEDICAL ASSOC PI KARACHI PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN SN 0030-9982 J9 J PAK MED ASSOC JI J. Pak. Med. Assoc. PD JAN PY 2011 VL 61 IS 1 BP 94 EP 95 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 696NI UT WOS:000285447700026 PM 22368916 ER PT J AU Ahmad, IM Britigan, BE Abdalla, MY AF Ahmad, Iman M. Britigan, Bradley E. Abdalla, Maher Y. TI Oxidation of Thiols and Modification of Redox-Sensitive Signaling in Human Lung Epithelial Cells Exposed to Pseudomonas pyocyanin SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID GLUTATHIONE DISULFIDE; SUPEROXIDE-DISMUTASE; AERUGINOSA; THIOREDOXIN; STRESS; PATHOGENESIS; MECHANISMS; REDUCTASE; CANCER; LESION AB The aim of this study was to examine the effects of pyocyanin exposure on mitochondrial GSH, other cellular thiols (thioredoxin-1, Trx-1), and oxidant-sensitive signaling pathways hypoxia inducible factor (HIF-1) and heme oxygenase (HO-1) in A549 and HBE cell lines. A549 human type II alveolar epithelial cells and human bronchial epithelial (HBE) cells were treated with varying concentrations of pyocyanin extracted from Pseudomonas aeruginosa bacteria. Cytoplasmic and mitochondrial thiols and oxidant sensitive signal transduction proteins (HIF-1 and HO-1) were measured. Exposure to pyocyanin generated reactive oxygen species (ROS) in cellular mitochondria and altered total cellular glutathione (GSH). Pyocyanin, at concentrations present in conditions in vivo, increased oxidized Trx-1 in A549 human type II alveolar epithelial cells and HBE cells by 184 and 74%, respectively. Oxidized mitochondrial glutathione (GSSG) was elevated more than twofold in both cell types. Pyocyanin also increased the cellular oxidant-sensitive proteins HIF-1 and HO-1. Data indicate that pyocyanin-induced alterations in mitochondrial and cytosolic thiols, as well as oxidant-sensitive proteins, may contribute to P. aeruginosa-mediated lung injury. C1 [Ahmad, Iman M.] Hashemite Univ, Dept Radiog, Zarqa, Jordan. [Britigan, Bradley E.] VA Med Ctr Cincinnati, Dept Internal Med, Cincinnati, OH USA. [Britigan, Bradley E.] Univ Cincinnati, Coll Med, Dept Internal Med, Cincinnati, OH USA. [Britigan, Bradley E.] Univ Cincinnati, Coll Med, Pathobiol Program, Cincinnati, OH USA. [Abdalla, Maher Y.] Hashemite Univ, Dept Biol & Biotechnol, Zarqa, Jordan. RP Abdalla, MY (reprint author), NCI, Ctr Canc Res, Natl Naval Med Ctr, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM Abdallamy@mail.nih.gov FU NIH [AI34954, AI60770]; VA Research service FX This work was supported in part by grants from the NIH (AI34954 and AI60770) and VA Research service to BEB. The authors thank Yunxia O'Malley for technical assistance in the development and performance of the HO-1 and transcription factor protocols. NR 34 TC 5 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2011 VL 74 IS 1 BP 43 EP 51 AR PII 930334692 DI 10.1080/15287394.2010.514233 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 687GJ UT WOS:000284766700003 PM 21120747 ER PT J AU Fadahunsi, AT Sanford, T Linehan, WM Pinto, PA Bratslavsky, G AF Fadahunsi, Amaka T. Sanford, Thomas Linehan, W. Marston Pinto, Peter A. Bratslavsky, Gennady TI Feasibility and Outcomes of Partial Nephrectomy for Resection of at Least 20 Tumors in a Single Renal Unit SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; nephrectomy; complications; neoplasms, multiple primary ID PARENCHYMAL SPARING SURGERY; HIPPEL-LINDAU-DISEASE; CELL CARCINOMA; INSUFFICIENCY; EXPERIENCE; CANCER; SIZE AB Purpose: Patients with hereditary renal cancer are at increased risk for recurrent bilateral multifocal tumors and may require aggressive nephron sparing surgery to prevent renal replacement therapy. We evaluated feasibility and outcomes in patients who underwent partial nephrectomy with removal of at least 20 tumors in a single renal unit at 1 setting. Materials and Methods: We retrospectively reviewed the records of 30 patients who underwent a total of 34 partial nephrectomies with removal of at least 20 tumors at our institution from 1993 to 2008. Operative reports and hospital records were reviewed for perioperative data, and renal functional and oncologic outcomes. We compared preoperative and postoperative renal function with the 2-tailed t test. Results: There were no deaths and only 1 renal unit was lost. A median of 26.5 tumors was removed. Median estimated blood loss was 3,500 ml and median operative time was 9 hours. Perioperative complications developed in greater than 50% of cases. There was a statistically significant decrease in the estimated glomerular filtration rate at 3 months (67 vs 59 ml/minute/1.73 m(2), p < 0.001). Only 1 patient had metastatic disease. Eight of the 34 operated kidneys required subsequent intervention during the median followup of 52 months (range 4 to 187). Conclusions: Aggressive partial nephrectomy to resect multiple tumors is technically feasible. There was a significant decrease in postoperative renal function but more than 80% of preoperative renal function was preserved in this cohort except in 1 patient. Also, oncologic outcomes were encouraging at intermediate term followup. C1 [Fadahunsi, Amaka T.; Sanford, Thomas; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1107,Bldg 10,CRC,Room 2W 5942, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research Intramural Research Program FX Supported by the National Institutes of Health, National Cancer Institute, Center for Cancer Research Intramural Research Program. NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2011 VL 185 IS 1 BP 49 EP 53 DI 10.1016/j.juro.2010.09.032 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 692GS UT WOS:000285141900012 PM 21074206 ER PT J AU Singer, EA Srinivasan, R Bratslavsky, G AF Singer, Eric A. Srinivasan, Ramaprasad Bratslavsky, Gennady TI The Impact of Cytoreductive Nephrectomy on Survival of Patients With Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Targeted Therapy EDITORIAL COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Singer, Eric A.; Srinivasan, Ramaprasad; Bratslavsky, Gennady] NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Singer, EA (reprint author), NIH, Urol Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2011 VL 185 IS 1 BP 66 EP 66 DI 10.1016/j.juro.2010.09.138 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 692GS UT WOS:000285141900016 PM 21074200 ER PT J AU Kemmerich, K Drechsler, M Weber, C Murphy, PM Sohnlein, O AF Kemmerich, K. Drechsler, M. Weber, C. Murphy, P. M. Soehnlein, O. TI Lack of Formyl-peptide receptor 1 reduces atherosclerotic lesion formation SO JOURNAL OF VASCULAR RESEARCH LA English DT Meeting Abstract CT Joint Meeting of the European-Society-for-Microcirculation (ESM)/Society-of-Microcirculation-and-Vascular-Biology (GfMVB) CY OCT 13-16, 2011 CL Ludwig Maximilians Univ, Munich, GERMANY SP European Soc Microcirculat, Soc Microcirculat & Vasc Biol HO Ludwig Maximilians Univ C1 [Kemmerich, K.; Drechsler, M.; Weber, C.; Soehnlein, O.] Univ Munich, Inst Cardiovasc Prevent, Munich, Germany. [Murphy, P. M.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PY 2011 VL 48 SU 1 BP 102 EP 102 PG 1 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 818NZ UT WOS:000294760800099 ER PT J AU Ogawa, H Miyamoto, H Ebihara, H Ito, K Morikawa, S Feldmann, H Takada, A AF Ogawa, Hirohito Miyamoto, Hiroko Ebihara, Hideki Ito, Kimihito Morikawa, Shigeru Feldmann, Heinz Takada, Ayato TI Detection of all known filovirus species by reverse transcription-polymerase chain reaction using a primer set specific for the viral nucleoprotein gene SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Filovirus; Marburg virus; Ebola virus; Diagnosis; RT-PCR ID MEDIATED ISOTHERMAL AMPLIFICATION; MARBURG HEMORRHAGIC-FEVER; EBOLA-VIRUS; RAPID DETECTION; ASSAY; RNA AB The filoviruses, Marburg virus (MARV) and Ebola virus (EBOV), are causative agents of severe hemorrhagic fever with high mortality rates in humans and non-human primates. Sporadic outbreaks of filovirus infection have occurred in Central Africa and parts of Asia. Identification of the natural reservoir animals that are unknown yet and epidemiological investigations are current challenges to forestall outbreaks of filovirus diseases. The filovirus species identified currently include one in the MARV group and five in the EBOV group, with large genetic variations found among the species. Therefore, it has been difficult to develop a single sensitive assay to detect all filovirus species, which would advance laboratory diagnosis greatly in endemic areas. In this study, a highly sensitive universal RT-PCR assay targeting the nucleoprotein (NP) gene of filoviruses was developed. The genomic RNAs of all known MARV and EBOV species were detected by using an NP-specific primer set. In addition, this RT-PCR procedure was verified further for its application to detect viral RNAs in tissue samples of animals infected experimentally and blood specimens of infected patients. This assay will be a useful method for diagnostics and epidemiological studies of filovirus infections. (C) 2010 Elsevier B.V. All rights reserved. C1 [Takada, Ayato] Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Kita Ku, Sapporo, Hokkaido 0010020, Japan. [Ogawa, Hirohito] Univ Zambia, Sch Vet Med, Hokudai Ctr Zoonosis Control Zambia, Lusaka, Zambia. [Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. [Morikawa, Shigeru] Natl Inst Infect Dis, Dept Virol 1, Tokyo, Japan. RP Takada, A (reprint author), Hokkaido Univ, Dept Global Epidemiol, Res Ctr Zoonosis Control, Kita Ku, Kita 20,Nishi 10, Sapporo, Hokkaido 0010020, Japan. EM atakada@czc.hokudai.ac.jp RI Takada, Ayato/A-6679-2012; Ito, Kimihito/E-9975-2012 OI Ito, Kimihito/0000-0003-4986-1795 FU Ministry of Health, Labor and Welfare of Japan; Founding Research Centers for Emerging and Reemerging Infectious Diseases; Ministry of Education, Culture, Sports, Science, and Technology, Japan; National Microbiology Laboratory of the Public Health Agency of Canada; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health FX We thank Aiko Ohnuma for technical assistance and Kim Barrymore for editing the manuscript. We also thank the Special Pathogens Branch, Centers for Disease Control and Prevention, and Dr. Jiro Arikawa and Dr. Kumiko Yoshimatsu (Hokkaido University), Dr. Kouichi Morita (Nagasaki University), and Dr. Nobuo Koizumi (National Institute of Infectious Diseases) for providing the Bundibugyo ebolavirus isolate, hantavirus, dengue 2 virus, and leptospira RNAs, respectively. This work was supported by a grant-in-aid from the Ministry of Health, Labor and Welfare of Japan, and in part by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases and the Global CUE Program "Establishment of International Collaboration Centers for Zoonosis Control" from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. In addition, the study was supported by the National Microbiology Laboratory of the Public Health Agency of Canada, and the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institute of Health. NR 19 TC 12 Z9 16 U1 2 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 EI 1879-0984 J9 J VIROL METHODS JI J. Virol. Methods PD JAN PY 2011 VL 171 IS 1 BP 310 EP 313 DI 10.1016/j.jviromet.2010.11.010 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 715AC UT WOS:000286851800053 PM 21093485 ER PT J AU Lau, YF Santos, C Torres-Velez, FJ Subbarao, K AF Lau, Yuk-Fai Santos, Celia Torres-Velez, Fernando J. Subbarao, Kanta TI The Magnitude of Local Immunity in the Lungs of Mice Induced by Live Attenuated Influenza Vaccines Is Determined by Local Viral Replication and Induction of Cytokines SO JOURNAL OF VIROLOGY LA English DT Article ID CD8(+) T-CELLS; CULTURE-CONFIRMED INFLUENZA; A VIRUS; PANDEMIC INFLUENZA; YOUNG-CHILDREN; RESPIRATORY-TRACT; RESPONSES; PROTECTION; MEMORY; INFECTION AB While live attenuated influenza vaccines (LAIVs) have been shown to be efficacious and have been licensed for human use, the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) have to be updated for optimal protective efficacy. Little is known about the effect of different HA and NA proteins on the immunogenicity of LAIVs developed using the same backbone. A panel of LAIVs that share the internal protein genes, with unique HA and NA gene segments from different influenza subtypes, was rescued by reverse genetics, and a comparative study of immune responses induced by these vaccines was conducted in mice. The results suggest that the magnitude of lung immunity, including pulmonary IgA antibody and memory CD8(+) T lymphocytes, induced by the vaccines depends on the replication efficiency of the LAIVs, as well as the induction of cytokines/chemokines in the lungs. However, these factors are not important in determining systemic immunity such as serum antibody titers and memory CD8(+) T cells in the spleen. A qualitative analysis of immune responses induced by a single dose of an H5N1 LAIV revealed that the vaccine induced robust systemic and mucosal immunity in mice. In addition, antibodies and memory lymphocytes established in the lungs following vaccination were required for protection against lethal challenge with homologous and heterologous H5N1 viruses. Our results highlight the different requirements for inducing systemic and lung immunity that can be explored for the development of pulmonary immunity for protection against respiratory pathogens. C1 [Lau, Yuk-Fai; Santos, Celia; Torres-Velez, Fernando J.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Lau, Yuk-Fai] DSO Natl Labs, DMERI, Med Countermeasures Biol Lab, Singapore 117510, Singapore. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C1,33 N Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU NIAID, NIH FX This research was supported by funds from the Intramural Research Program of the NIAID, NIH. NR 47 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 76 EP 85 DI 10.1128/JVI.01564-10 PG 10 WC Virology SC Virology GA 691QL UT WOS:000285095800006 PM 20962087 ER PT J AU Santiago, ML Smith, DS Barrett, BS Montano, M Benitez, RL Pelanda, R Hasenkrug, KJ Greene, WC AF Santiago, Mario L. Smith, Diana S. Barrett, Bradley S. Montano, Mauricio Benitez, Robert L. Pelanda, Roberta Hasenkrug, Kim J. Greene, Warner C. TI Persistent Friend Virus Replication and Disease in Apobec3-Deficient Mice Expressing Functional B-Cell-Activating Factor Receptor SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA DECAY; MURINE LEUKEMIA-VIRUS; HOST GENETIC-CONTROL; MOUSE-CHROMOSOME 15; RETROVIRUS INFECTION; SURFACE ANTIGENS; RESISTANCE GENE; RFV-3 GENE; IN-VIVO; BAFF-R AB Rfv3 is an autosomal dominant gene that influences the recovery of resistant mice from Friend retrovirus (FV) infection by limiting viremia and promoting a more potent neutralizing antibody response. We previously reported that Rfv3 is encoded by Apobec3, an innate retrovirus restriction factor. However, it was recently suggested that the Rfv3 susceptible phenotype of high viremia at 28 days postinfection (dpi) was more dominantly controlled by the B-cell-activating factor receptor (BAFF-R), a gene that is linked to but located outside the genetically mapped region containing Rfv3. Although one prototypical Rfv3 susceptible mouse strain, A/WySn, indeed contains a dysfunctional BAFF-R, two other Rfv3 susceptible strains, BALB/c and A. BY, express functional BAFF-R genes, determined on the basis of genotyping and B-cell immunophenotyping. Furthermore, transcomplementation studies in (C57BL/6 [B6] x BALB/c) F-1 and (B6 x A. BY) F-1 mice revealed that the B6 Apobec3 gene significantly influences recovery from FV viremia, cellular infection, and disease at 28 dpi. Finally, the Rfv3 phenotypes of prototypic B6, A.BY, A/WySn, and BALB/c mouse strains correlate with reported Apobec3 mRNA expression levels. Overall, these findings argue against the generality of BAFF-R polymorphisms as a dominant mechanism to explain the Rfv3 recovery phenotype and further strengthen the evidence that Apobec3 encodes Rfv3. C1 [Santiago, Mario L.] Univ Colorado Denver, Div Infect Dis, Dept Med, Aurora, CO 80045 USA. [Smith, Diana S.] Univ Colorado Denver, Dept Microbiol, Aurora, CO 80045 USA. [Santiago, Mario L.; Pelanda, Roberta] Univ Colorado Denver, Dept Immunol, Aurora, CO 80045 USA. [Montano, Mauricio; Benitez, Robert L.; Greene, Warner C.] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. [Greene, Warner C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Greene, Warner C.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94158 USA. [Pelanda, Roberta] Natl Jewish Hlth, Denver, CO 80206 USA. [Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Santiago, ML (reprint author), Univ Colorado Denver, Div Infect Dis, Dept Med, Mail Stop B-168,12700 E 19th Ave, Aurora, CO 80045 USA. EM mario.santiago@ucdenver.edu OI Santiago, Mario L./0000-0001-7792-2706 FU National Institutes of Health [R56 AI-0841230, R01 AI090795, R01 A065329] FX This work was supported by National Institutes of Health grants R56 AI-0841230 and R01 AI090795 (to M. L. S.) and R01 A065329 (to W. C. G.). NR 50 TC 14 Z9 15 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 189 EP 199 DI 10.1128/JVI.01838-10 PG 11 WC Virology SC Virology GA 691QL UT WOS:000285095800016 PM 20980520 ER PT J AU Sheahan, T Whitmore, A Long, K Ferris, M Rockx, B Funkhouser, W Donaldson, E Gralinski, L Collier, M Heise, M Davis, N Johnston, R Baric, RS AF Sheahan, Timothy Whitmore, Alan Long, Kristin Ferris, Martin Rockx, Barry Funkhouser, William Donaldson, Eric Gralinski, Lisa Collier, Martha Heise, Mark Davis, Nancy Johnston, Robert Baric, Ralph S. TI Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus SO JOURNAL OF VIROLOGY LA English DT Article ID EQUINE ENCEPHALITIS-VIRUS; HEALTHY ELDERLY POPULATION; CELLULAR IMMUNE-RESPONSES; SARS-CORONAVIRUS; HONG-KONG; ANTIBODY-RESPONSE; S-PROTEIN; IN-VITRO; T-CELLS; INFECTION AB Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future. C1 [Sheahan, Timothy; Rockx, Barry; Donaldson, Eric; Gralinski, Lisa; Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27699 USA. [Sheahan, Timothy; Heise, Mark; Davis, Nancy; Johnston, Robert; Baric, Ralph S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27699 USA. [Whitmore, Alan; Long, Kristin; Ferris, Martin; Collier, Martha; Heise, Mark; Davis, Nancy; Johnston, Robert] Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC 27699 USA. [Funkhouser, William] Univ N Carolina, Sch Med, Dept Pathol, Chapel Hill, NC 27699 USA. [Heise, Mark] Univ N Carolina, Dept Genet, Chapel Hill, NC 27699 USA. [Rockx, Barry] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Baric, RS (reprint author), Univ N Carolina, Dept Epidemiol, 2107 McGavran Greenberg,CB7435, Chapel Hill, NC 27699 USA. EM rbaric@email.unc.edu FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [PO1 AI59443, SERCEB U54 AI057157] FX This work was supported by research grant PO1 AI59443 to R. S. B., R.E.J., and M. T. H. and by SERCEB U54 AI057157 from the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 70 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 217 EP 230 DI 10.1128/JVI.01805-10 PG 14 WC Virology SC Virology GA 691QL UT WOS:000285095800019 PM 20980507 ER PT J AU Ramalingam, D Duclair, S Datta, SAK Ellington, A Rein, A Prasad, VR AF Ramalingam, Dhivya Duclair, Sonald Datta, Siddhartha A. K. Ellington, Andrew Rein, Alan Prasad, Vinayaka R. TI RNA Aptamers Directed to Human Immunodeficiency Virus Type 1 Gag Polyprotein Bind to the Matrix and Nucleocapsid Domains and Inhibit Virus Production SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 CAPSID PROTEIN; ACID-CHAPERONE ACTIVITY; IN-VITRO; EXPONENTIAL ENRICHMENT; SYSTEMATIC EVOLUTION; CRYSTAL-STRUCTURE; GENOMIC RNA; MXA GTPASE; REPLICATION; CELLS AB Gag orchestrates the assembly and release of human immunodeficiency virus type 1 (HIV-1) particles. We explored here the potential of anti-Gag RNA aptamers to inhibit HIV-1 replication. In vitro, RNA aptamers raised against an HIV-1 Gag protein, lacking the N-terminal myristate and the C-terminal p6 (DP6-Gag), could bind to matrix protein (MA), nucleocapsid protein (NC), or entire DP6-Gag protein. Upon cotransfection with pNL4-3.Luc molecular clone into 293T cells, six of the aptamers caused mild inhibition (2- to 3-fold) in the extracellular capsid levels, and one aptamer displayed 20-fold inhibition. The reduction was not due to a release defect but reflected Gag mRNA levels. We hypothesized that the aptamers influence genomic RNA levels via perturbation of specific Gag-genomic RNA interactions. Binding studies revealed that the "NC-binders" specifically compete with the packaging signal (psi) of HIV-1 for binding to DP6-Gag. Therefore, we tested the ability of two NC-binders to inhibit viruses containing psi-region deletions (Delta SL1 or Delta SL3) and found that the NC-binders were no longer able to inhibit Gag synthesis. The inability of these aptamers to inhibit psi-deleted viruses correlated with the absence of competition with the corresponding psi transcripts lacking SL1 or SL3 for binding DP6-Gag in vitro. These results indicate that the NC-binding aptamers disrupt Gag-genomic RNA interaction and negatively affect genomic RNA transcription, processing, or stability. Our results reveal an essential interaction between HIV-1 Gag and the psi-region that may be distinct from that which occurs during the encapsidation of genomic RNA. Thus, anti-Gag aptamers can be an effective tool to perturb Gag-genomic RNA interactions. C1 [Ellington, Andrew] Univ Texas Austin, Dept Chem & Biochem, Austin, TX 78712 USA. [Datta, Siddhartha A. K.; Rein, Alan] 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 vinayaka.prasad@einstein.yu.edu OI Datta, Siddhartha/0000-0002-4098-7490 FU NIH [T32 AI007501, F31-GM78730, R37AI030861, P01 AI 061797]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX S.D. was supported by an institutional NIH AIDS training grant (T32 AI007501) and an NIH MARC fellowship (F31-GM78730). The research described in this report was supported by NIH grants R37AI030861 and P01 AI 061797 to V.R.P. and in part by the Intramural Research Program at the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 46 TC 38 Z9 42 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 305 EP 314 DI 10.1128/JVI.02626-09 PG 10 WC Virology SC Virology GA 691QL UT WOS:000285095800027 PM 20980522 ER PT J AU Majumdar, A Chatterjee, AG Ripmaster, TL Levin, HL AF Majumdar, Anasuya Chatterjee, Atreyi Ghatak Ripmaster, Tracy L. Levin, Henry L. TI Determinants That Specify the Integration Pattern of Retrotransposon Tf1 in the fbp1 Promoter of Schizosaccharomyces pombe SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-III; PROTEIN-KINASE-A; FISSION YEAST; HIV-1 INTEGRASE; COACTIVATOR P75; DNA INTEGRATION; HUMAN GENOME; HUMAN-CELLS; LEDGF/P75; TRANSCRIPTION AB Long terminal repeat (LTR) retrotransposons are closely related to retroviruses and, as such, are important models for the study of viral integration and target site selection. The transposon Tf1 of Schizosaccharomyces pombe integrates with a strong preference for the promoters of polymerase II (Pol II)-transcribed genes. Previous work in vivo with plasmid-based targets revealed that the patterns of insertion were promoter specific and highly reproducible. To determine which features of promoters are recognized by Tf1, we studied integration in a promoter that has been characterized. The promoter of fbp1 has two upstream activating sequences, UAS1 and UAS2. We found that integration was targeted to two windows, one 180 nucleotides (nt) upstream and the other 30 to 40 nt downstream of UAS1. A series of deletions in the promoter showed that the integration activities of these two regions functioned autonomously. Integration assays of UAS2 and of a synthetic promoter demonstrated that strong promoter activity alone was not sufficient to direct integration. The factors that modulate the transcription activities of UAS1 and UAS2 include the activators Atf1p, Pcr1p, and Rst2p as well as the repressors Tup11p, Tup12p, and Pka1p. Strains lacking each of these proteins revealed that Atf1p alone mediated the sites of integration. These data indicate that Atf1p plays a direct and specific role in targeting integration in the promoter of fbp1. C1 [Majumdar, Anasuya; Chatterjee, Atreyi Ghatak; Ripmaster, Tracy L.; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bldg 6B,Room 222, Bethesda, MD 20892 USA. EM henry_levin@nih.gov FU NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 38 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 1 BP 519 EP 529 DI 10.1128/JVI.01719-10 PG 11 WC Virology SC Virology GA 691QL UT WOS:000285095800047 PM 20980525 ER PT J AU Nelson, MI Tan, Y Ghedin, E Wentworth, DE St George, K Edelman, L Beck, ET Fan, JA Lam, TTY Kumar, S Spiro, DJ Simonsen, L Viboud, C Holmes, EC Henrickson, KJ Musser, JM AF Nelson, Martha I. Tan, Yi Ghedin, Elodie Wentworth, David E. St George, Kirsten Edelman, Laurel Beck, Eric T. Fan, Jiang Lam, Tommy Tsan-Yuk Kumar, Swati Spiro, David J. Simonsen, Lone Viboud, Cecile Holmes, Edward C. Henrickson, Kelly J. Musser, James M. TI Phylogeography of the Spring and Fall Waves of the H1N1/09 Pandemic Influenza Virus in the United States SO JOURNAL OF VIROLOGY LA English DT Article ID NEW-YORK-CITY; A H1N1; MILWAUKEE; WISCONSIN; EPIDEMIC; OUTBREAK; HUMANS; SCHOOL AB Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes such an approach possible. To determine whether the spring and fall waves of the H1N1/09 influenza pandemic were associated with different epidemiological patterns, we undertook a large-scale phylogeographic analysis of viruses sampled from three localities in the United States. Analysis of genomic and epidemiological data reveals distinct spatial heterogeneities associated with the first pandemic wave, March to July 2009, in Houston, TX, Milwaukee, WI, and New York State. In Houston, no specific H1N1/09 viral lineage dominated during the spring of 2009, a period when little epidemiological activity was observed in Texas. In contrast, major pandemic outbreaks occurred at this time in Milwaukee and New York State, each dominated by a different viral lineage and resulting from strong founder effects. During the second pandemic wave, beginning in August 2009, all three U.S. localities were dominated by a single viral lineage, that which had been dominant in New York during wave 1. Hence, during this second phase of the pandemic, extensive viral migration and mixing diffused the spatially defined population structure that had characterized wave 1, amplifying the one viral lineage that had dominated early on in one of the world's largest international travel centers. C1 [Nelson, Martha I.; Tan, Yi; Simonsen, Lone; Viboud, Cecile; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ghedin, Elodie] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Ctr Vaccine Res, Pittsburgh, PA USA. [Ghedin, Elodie; Spiro, David J.] J Craig Venter Inst, Rockville, MD USA. [Wentworth, David E.; St George, Kirsten] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Wentworth, David E.] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA. [Edelman, Laurel] Surveillance Data Inc, Plymouth Meeting, PA USA. [Beck, Eric T.; Fan, Jiang; Kumar, Swati; Henrickson, Kelly J.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Milwaukee, WI 53226 USA. [Lam, Tommy Tsan-Yuk; Holmes, Edward C.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA. [Musser, James M.] Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. [Musser, James M.] Methodist Hosp, Dept Pathol & Lab Med, Houston, TX 77030 USA. RP Nelson, MI (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr,Bldg 16,Room 202, Bethesda, MD 20892 USA. EM nelsonma@mail.nih.gov RI Lam, Tommy Tsan-Yuk/D-4837-2012; Chiang, Vincent, Ming-Hsien/D-4312-2016; OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863; Wentworth, David/0000-0002-5190-980X; Simonsen, Lone/0000-0003-1535-8526; Holmes, Edward/0000-0001-9596-3552 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services [HHSN272200900007C]; NIAID [UO1-AI070428, U01-387 AI077988, U01-AI066584]; Influenza Genome Sequencing Project; Office of Global Health Affairs' International Influenza Unit in the Office of the Secretary of the Department of Health and Human Services FX This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services, under contract number HHSN272200900007C and by NIAID grants UO1-AI070428, U01-387 AI077988, and U01-AI066584. The whole-genome sequencing of viral samples from Houston, Milwaukee, and New York State was funded by the Influenza Genome Sequencing Project, administered by NIAID/NIH. This research was conducted in the context of the MISMS study, an ongoing international collaborative effort to understand influenza epidemiological and evolutionary patterns, led by the Fogarty International Center, National Institutes of Health (www.origem.info/misms). Funding for the MISMS project comes in part from the Office of Global Health Affairs' International Influenza Unit in the Office of the Secretary of the Department of Health and Human Services. NR 26 TC 29 Z9 30 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 828 EP 834 DI 10.1128/JVI.01762-10 PG 7 WC Virology SC Virology GA 697XY UT WOS:000285554300018 PM 21068250 ER PT J AU Kobayashi, T Ode, H Yoshida, T Sato, K Gee, P Yamamoto, SP Ebina, H Strebel, K Sato, H Koyanagi, Y AF Kobayashi, Tomoko Ode, Hirotaka Yoshida, Takeshi Sato, Kei Gee, Peter Yamamoto, Seiji P. Ebina, Hirotaka Strebel, Klaus Sato, Hironori Koyanagi, Yoshio TI Identification of Amino Acids in the Human Tetherin Transmembrane Domain Responsible for HIV-1 Vpu Interaction and Susceptibility SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOLECULAR-DYNAMICS SIMULATIONS; PARTICLE MESH EWALD; AMBER FORCE-FIELD; TYPE-1 VPU; FLUORESCENCE COMPLEMENTATION; PROTEIN INTERACTIONS; MEMBRANE-PROTEIN; CELL-SURFACE; LIVING CELLS AB Tetherin, also known as BST-2/CD317/HM1.24, is an antiviral cellular protein that inhibits the release of HIV-1 particles from infected cells. HIV-1 viral protein U (Vpu) is a specific antagonist of human tetherin that might contribute to the high virulence of HIV-1. In this study, we show that three amino acid residues (I34, L37, and L41) in the transmembrane (TM) domain of human tetherin are critical for the interaction with Vpu by using a live cell-based assay. We also found that the conservation of an additional amino acid at position 45 and two residues downstream of position 22, which are absent from monkey tetherins, are required for the antagonism by Vpu. Moreover, computer-assisted structural modeling and mutagenesis studies suggest that an alignment of these four amino acid residues (I34, L37, L41, and T45) on the same helical face in the TM domain is crucial for the Vpu-mediated antagonism of human tetherin. These results contribute to the molecular understanding of human tetherin-specific antagonism by HIV-1 Vpu. C1 [Kobayashi, Tomoko; Yoshida, Takeshi; Sato, Kei; Gee, Peter; Yamamoto, Seiji P.; Ebina, Hirotaka; Koyanagi, Yoshio] Kyoto Univ, Lab Viral Pathogenesis, Inst Virus Res, Sakyo Ku, Kyoto 6068507, Japan. [Ode, Hirotaka; Sato, Hironori] Natl Inst Infect Dis, Pathogen Genom Ctr, Tokyo 2080011, Japan. [Yoshida, Takeshi; Strebel, Klaus] NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. [Yamamoto, Seiji P.] Kyoto Univ, Dept Mol & Cellular Biol, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068507, Japan. RP Koyanagi, Y (reprint author), Kyoto Univ, Lab Viral Pathogenesis, Inst Virus Res, Sakyo Ku, 53 Shogoin Kawahara Cho, Kyoto 6068507, Japan. EM ykoyanag@virus.kyoto-u.ac.jp RI Gee, Peter/H-5681-2013 FU Ministry of Education, Culture, Sports and Technology of Japan; Health and Labor Science research; Ministry of Health, Labor and Welfare of Japan; Japan Society for the Promotion of Science for Young Scientists FX This work was supported by Grants-in-Aid for Science Research of Priority Areas from the Ministry of Education, Culture, Sports and Technology of Japan, a Health and Labor Science research grant (Research on Publicly Essential Drugs and Medical Devices) and a grant for HIV/AIDS research from the Ministry of Health, Labor and Welfare of Japan. K.S., T.Y., and S.P.Y. were supported by research fellowships from the Japan Society for the Promotion of Science for Young Scientists. NR 71 TC 60 Z9 61 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 932 EP 945 DI 10.1128/JVI.01668-10 PG 14 WC Virology SC Virology GA 697XY UT WOS:000285554300029 PM 21068238 ER PT J AU Kearney, M Spindler, J Shao, W Maldarelli, F Palmer, S Hu, SL Lifson, JD KewalRamani, VN Mellors, JW Coffin, JM Ambrose, Z AF Kearney, Mary Spindler, Jon Shao, Wei Maldarelli, Frank Palmer, Sarah Hu, Shiu-Lok Lifson, Jeffrey D. KewalRamani, Vineet N. Mellors, John W. Coffin, John M. Ambrose, Zandrea TI Genetic Diversity of Simian Immunodeficiency Virus Encoding HIV-1 Reverse Transcriptase Persists in Macaques despite Antiretroviral Therapy SO JOURNAL OF VIROLOGY LA English DT Article ID LOW-LEVEL VIREMIA; INFECTED PATIENTS; DRUG-RESISTANCE; LYMPHOID-TISSUE; GENOTYPIC RESISTANCE; COMBINATION THERAPY; VIROLOGICAL FAILURE; VIRAL SUPPRESSION; RESIDUAL VIREMIA; TYPE-1 AB The impact of antiretroviral therapy (ART) on the genetics of simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) populations has been incompletely characterized. We analyzed SIV genetic variation before, during, and after ART in a macaque model. Six pigtail macaques were infected with an SIV/HIV chimeric virus, RT-SHIV(mne), in which SIV reverse transcriptase (RT) was replaced by HIV-1 RT. Three animals received a short course of efavirenz (EFV) monotherapy before combination ART was started. All macaques received 20 weeks of tenofovir, emtricitabine, and EFV. Plasma virus populations were analyzed by single-genome sequencing. Population diversity was measured by average pairwise difference, and changes in viral genetics were assessed by phylogenetic and panmixia analyses. After 20 weeks of ART, viral diversity was not different from pretherapy viral diversity despite more than 10,000-fold declines in viremia, indicating that, within this range, there is no relationship between diversity and plasma viremia. In two animals with consistent SIV RNA suppression to <15 copies/ml during ART, there was no evidence of viral evolution. In contrast, in the four macaques with viremias >15 copies/ml during therapy, there was divergence between pre- and during-ART virus populations. Drug resistance mutations emerged in two of these four animals, resulting in virologic failure in the animal with the highest level of pretherapy viremia. Taken together, these findings indicate that viral diversity does not decrease with suppressive ART, that ongoing replication occurs with viremias >15 copies/ml, and that in this macaque model of ART drug resistance likely emerges as a result of incomplete suppression and preexisting drug resistance mutations. C1 [Kearney, Mary; Spindler, Jon; Maldarelli, Frank; KewalRamani, Vineet N.; Coffin, John M.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Shao, Wei] SAIC, Adv Biomed Comp Ctr, Frederick, MD USA. [Palmer, Sarah] Karolinska Inst, Swedish Inst Infect Dis Control, Stockholm, Sweden. [Hu, Shiu-Lok] Washington Natl Primate Res Ctr, Seattle, WA USA. [Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Mellors, John W.; Ambrose, Zandrea] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. RP Kearney, M (reprint author), NCI, HIV Drug Resistance Program, 1050 Boyles St,Bldg 535,Room 109, Frederick, MD 21702 USA. EM kearneym@ncifcrf.gov FU National Cancer Institute's intramural Center for Cancer Research; NIH [R01, AI080290]; SAIC [25XS119]; National Cancer Institute, NIH [HHSN261200800001E]; American Cancer Society FX Funding for this research was provided by the National Cancer Institute's intramural Center for Cancer Research, by NIH R01 grant AI080290 (Z.A.), by SAIC contract 25XS119 (J.W.M.), and in part by federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. J.M.C. was a recipient of a Research Professorship from the American Cancer Society with support from the George Kirby Foundation. NR 42 TC 27 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 1067 EP 1076 DI 10.1128/JVI.01701-10 PG 10 WC Virology SC Virology GA 697XY UT WOS:000285554300041 PM 21084490 ER PT J AU Palermo, RE Patterson, LJ Aicher, LD Korth, MJ Robert-Guroff, M Katze, MG AF Palermo, Robert E. Patterson, L. Jean Aicher, Lauri D. Korth, Marcus J. Robert-Guroff, Marjorie Katze, Michael G. TI Genomic Analysis Reveals Pre- and Postchallenge Differences in a Rhesus Macaque AIDS Vaccine Trial: Insights into Mechanisms of Vaccine Efficacy SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; YELLOW-FEVER VACCINE; GENE-EXPRESSION; PROTECTIVE EFFICACY; INFLUENZA-VIRUS; SHIV89.6P CHALLENGE; FUNCTIONAL GENOMICS; HIV-1 INFECTION; VIRAL LOAD AB We have employed global transcriptional profiling of whole blood to identify biologically relevant changes in cellular gene expression in response to alternative AIDS vaccine strategies with subsequent viral challenge in a rhesus macaque vaccine model. Samples were taken at day 0 (prechallenge), day 14 (peak viremia), and week 12 (set point) from animals immunized with replicating adenovirus type 5 host range (Ad5hr) recombinant viruses expressing human immunodeficiency virus HIVenv89.6P, simian immunodeficiency virus SIVgag239, or SIVnef239 alone or in combination with two intramuscular boosts with HIV(89.6P)gp140 Delta CFI protein (L. J. Patterson et al., Virology 374:322-337, 2008), and each treatment resulted in significant control of viremia following simian-human immunodeficiency virus SHIV89.6P challenge (six animals per group plus six controls). At day 0, 8 weeks after the last treatment, the microarray profiles revealed significant prechallenge differences between treatment groups; data from the best-protected animals led to identification of a network of genes related to B cell development and lymphocyte survival. At peak viremia, expression profiles of the immunized groups were extremely similar, and comparisons to control animals reflected immunological differences other than effector T cell functions. Suggested protective mechanisms for vaccinated animals included upregulation of interleukin-27, a cytokine known to inhibit lentivirus replication, and increased expression of complement components, which may synergize with vaccine-induced antibodies. Divergent expression profiles at set point for the immunized groups implied distinct immunological responses despite phenotypic similarities in viral load and CD4(+) T cell levels. Data for the gp140-boosted group provided evidence for antibody-dependent, cell-mediated viral control, whereas animals immunized with only the replicating Ad5hr recombinants exhibited a different evolution of the B cell compartment even at 3 months postchallenge. This study demonstrates the sensitivity and discrimination of gene expression profiling of whole blood as an analytical tool in AIDS vaccine trials, providing unique insights into in vivo mechanisms and potential correlates of protection. C1 [Palermo, Robert E.; Aicher, Lauri D.; Korth, Marcus J.; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Palermo, Robert E.; Korth, Marcus J.; Katze, Michael G.] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Patterson, L. Jean; Robert-Guroff, Marjorie] NCI, Vaccine Branch, Bethesda, MD 20892 USA. RP Palermo, RE (reprint author), Univ Washington, Dept Microbiol, Box 358070, Seattle, WA 98195 USA. EM palermor@u.washington.edu FU National Institutes of Health [R21AI071892, P51RR000166]; NIH NIAID; Quality Biological, Inc., Gaithersburg, MD; National Institutes of Health, National Cancer Institute FX This work was supported by Public Health Service grants R21AI071892 and P51RR000166 from the National Institutes of Health; by the NIH NIAID AIDS Reference and Reagent Resource Support Program for AIDS Vaccine Development; by Quality Biological, Inc., Gaithersburg, MD; and in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute. NR 111 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 1099 EP 1116 DI 10.1128/JVI.01522-10 PG 18 WC Virology SC Virology GA 697XY UT WOS:000285554300044 PM 21068249 ER PT J AU Xing, L Wang, JC Li, TC Yasutomi, Y Lara, J Khudyakov, Y Schofield, D Emerson, SU Purcell, RH Takeda, N Miyamura, T Cheng, RH AF Xing, Li Wang, Joseph C. Li, Tian-Cheng Yasutomi, Yasuhiro Lara, James Khudyakov, Yury Schofield, Darren Emerson, Suzanne U. Purcell, Robert H. Takeda, Naokazu Miyamura, Tatsuo Cheng, R. Holland TI Spatial Configuration of Hepatitis E Virus Antigenic Domain SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; CAPSID PROTEIN; TRUNCATED ORF2; PARTICLES; VACCINE; EPITOPES; INFECTION; IDENTIFICATION; PROTECTION; CHALLENGE AB Hepatitis E virus (HEV) is a human pathogen that causes acute hepatitis. When an HEV capsid protein containing a 52-amino-acid deletion at the C terminus and a 111-amino-acid deletion at the N terminus is expressed in insect cells, the recombinant HEV capsid protein can self-assemble into a T=1 virus-like particle (VLP) that retains the antigenicity of the native HEV virion. In this study, we used cryoelectron microscopy and image reconstruction to show that anti-HEV monoclonal antibodies bind to the protruding domain of the capsid protein at the lateral side of the spikes. Molecular docking of the HEV VLP crystal structure revealed that Fab224 covered three surface loops of the recombinant truncated second open reading frame (ORF2) protein (PORF2) at the top part of the spike. We also determined the structure of a chimeric HEV VLP and located the inserted B-cell tag, an epitope of 11 amino acids coupled to the C-terminal end of the recombinant ORF2 protein. The binding site of Fab224 appeared to be distinct from the location of the inserted B-cell tag, suggesting that the chimeric VLP could elicit immunity against both HEV and an inserted foreign epitope. Therefore, the T=1 HEV VLP is a novel delivery system for displaying foreign epitopes at the VLP surface in order to induce antibodies against both HEV and the inserted epitope. C1 [Xing, Li; Wang, Joseph C.; Cheng, R. Holland] Univ Calif Davis, Davis, CA 95616 USA. [Xing, Li] F68 Univ Hosp, Karolinska Inst Struct Virol, SE-14186 Stockholm, Sweden. [Li, Tian-Cheng; Takeda, Naokazu; Miyamura, Tatsuo] Natl Inst Infect Dis, Dept Virol 2, Tokyo 162, Japan. [Yasutomi, Yasuhiro] Natl Inst Biomed Innovat, Tsukuba Primate Res Ctr, Ibaraki 3050843, Japan. [Lara, James; Khudyakov, Yury] Ctr Dis Control & Prevent, Div Viral Hepatitis, CDC, Atlanta, GA 30333 USA. [Schofield, Darren; Emerson, Suzanne U.; Purcell, Robert H.] NIAID, Hepatitis Virus Sect, Bethesda, MD USA. RP Cheng, RH (reprint author), Univ Calif Davis, 1 Shields Ave, Davis, CA 95616 USA. EM rhch@ucdavis.edu RI Cheng, Holland/A-8973-2008 FU STINT Foundation; Medical Research Council; PIOMS Institutional Program; Swedish Research Council; Cancer Research and Discovery Programs; NSC FX This project was supported in part by grants from the STINT Foundation, the Medical Research Council, and the PIOMS Institutional Program to R.H.C. This study was also partly funded by a grant from the Swedish Research Council to L.X. J.C.W. and L.X. were supported by grants from the Cancer Research and Discovery Programs, respectively. J.C.W. was initially supported by a grant from NSC as an exchange student under the cosupervision of D. M. Liou and Y. J. Sung. NR 33 TC 31 Z9 32 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 1117 EP 1124 DI 10.1128/JVI.00657-10 PG 8 WC Virology SC Virology GA 697XY UT WOS:000285554300045 PM 21068233 ER PT J AU Bila, C Oberhauser, V Ammann, CG Ejaz, A Huber, G Schimmer, S Messer, R Pekna, M von Laer, D Dittmer, U Hasenkrug, KJ Stoiber, H Banki, Z AF Bila, Custodio Oberhauser, Verena Ammann, Christoph G. Ejaz, Asim Huber, Georg Schimmer, Simone Messer, Ron Pekna, Marcela von Laer, Dorothee Dittmer, Ulf Hasenkrug, Kim J. Stoiber, Heribert Banki, Zoltan TI Complement Opsonization Enhances Friend Virus Infection of B Cells and Thereby Amplifies the Virus-Specific CD8(+) T Cell Response SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; DENDRITIC CELLS; IN-VIVO; RETROVIRUS INFECTION; MEDIATE INFECTION; CR-1 CD35; HIV; LYMPHOCYTES; CR3 AB B cells are one of the targets of Friend virus (FV) infection, a well-established mouse model often used to study retroviral infections in vivo. Although B cells may be effective in stimulating cytotoxic T lymphocyte responses, studies involving their role in FV infection have mainly focused on neutralizing antibody production. Here we show that polyclonal activation of B cells promotes their infection with FV both in vitro and in vivo. Furthermore, we demonstrate that complement opsonization of Friend murine leukemia virus (F-MuLV) enhances infection of B cells, which correlates with increased potency of B cells to activate FV-specific CD8(+) T cells. C1 [Bila, Custodio; Oberhauser, Verena; Ammann, Christoph G.; Ejaz, Asim; Huber, Georg; von Laer, Dorothee; Stoiber, Heribert; Banki, Zoltan] Innsbruck Med Univ, Div Virol, A-6020 Innsbruck, Austria. [Schimmer, Simone; Dittmer, Ulf] Univ Duisburg Essen, Inst Virol, Essen, Germany. [Messer, Ron; Hasenkrug, Kim J.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. [Pekna, Marcela] Gothenburg Univ, Dept Med Chem & Cell Biol, Inst Biomed, Sahlgrenska Acad, Gothenburg, Sweden. RP Banki, Z (reprint author), Innsbruck Med Univ, Div Virol, Fritz Pregl Str 3, A-6020 Innsbruck, Austria. EM zolta.banki@i-med.ac.at OI Pekna, Marcela/0000-0003-2734-8237; Ammann, Christoph/0000-0002-6267-1286 FU Austrian Science Fund (FWF) [P21508]; Innsbruck Medical University (MFI) [6400]; European Union [DEC-VAC 018685]; Deutsche Forschungsgemeinschaft [TRR60, B4] FX We are supported by the Austrian Science Fund (FWF; P21508 to Z.B.), the Innsbruck Medical University (MFI; 6400 to Z.B.), and the European Union (DEC-VAC 018685 to H.S.). Part of this work was supported by a grant from the Deutsche Forschungsgemeinschaft (TRR60 project B4 to U.D.). NR 31 TC 5 Z9 5 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2011 VL 85 IS 2 BP 1151 EP 1155 DI 10.1128/JVI.01821-10 PG 5 WC Virology SC Virology GA 697XY UT WOS:000285554300050 PM 21047954 ER PT J AU Harel, A Ullman, S Harari, D Bentin, S AF Harel, Assaf Ullman, Shimon Harari, Danny Bentin, Shlomo TI Basic-level categorization of intermediate complexity fragments reveals top-down effects of expertise in visual perception SO JOURNAL OF VISION LA English DT Article DE object recognition; categorization; visual cognition; expertise ID OBJECT RECOGNITION; FACE RECOGNITION; INFEROTEMPORAL CORTEX; NEURAL REPRESENTATION; DECISION-MAKING; PARTS; FEATURES; SHAPE; CLASSIFICATION; BRAIN AB Visual expertise is usually defined as the superior ability to distinguish between exemplars of a homogeneous category. Here, we ask how real-world expertise manifests at basic-level categorization and assess the contribution of stimulus-driven and top-down knowledge-based factors to this manifestation. Car experts and novices categorized computer-selected image fragments of cars, airplanes, and faces. Within each category, the fragments varied in their mutual information (MI), an objective quantifiable measure of feature diagnosticity. Categorization of face and airplane fragments was similar within and between groups, showing better performance with increasing MI levels. Novices categorized car fragments more slowly than face and airplane fragments, while experts categorized car fragments as fast as face and airplane fragments. The experts' advantage with car fragments was similar across MI levels, with similar functions relating RT with MI level for both groups. Accuracy was equal between groups for cars as well as faces and airplanes, but experts' response criteria were biased toward cars. These findings suggest that expertise does not entail only specific perceptual strategies. Rather, at the basic level, expertise manifests as a general processing advantage arguably involving application of top-down mechanisms, such as knowledge and attention, which helps experts to distinguish between object categories. C1 [Harel, Assaf] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Ullman, Shimon; Harari, Danny] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel. [Bentin, Shlomo] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. [Bentin, Shlomo] Hebrew Univ Jerusalem, Ctr Neural Computat, Jerusalem, Israel. RP Harel, A (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. OI Harel, Assaf/0000-0002-4899-6156 FU NIMH NIH HHS [R01 MH064458, R01 MH064458-09] NR 57 TC 9 Z9 9 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2011 VL 11 IS 8 AR 18 DI 10.1167/11.8.18 PG 13 WC Ophthalmology SC Ophthalmology GA 800QZ UT WOS:000293380600019 PM 21799022 ER PT J AU D'Orazio, LM Meyerowitz, BE Korst, LM Romero, R Goodwin, TM AF D'Orazio, Lina M. Meyerowitz, Beth E. Korst, Lisa M. Romero, Roberto Goodwin, Thomas M. TI Evidence Against a Link Between Hyperemesis Gravidarum and Personality Characteristics from an Ethnically Diverse Sample of Pregnant Women: A Pilot Study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PSYCHOLOGICAL-FACTORS; NAUSEA AB Background: Hyperemesis gravidarum (HG), a pregnancy-related condition marked by extreme nausea and vomiting, has been considered a psychosomatic illness associated with long-standing personality characteristics (e.g., hysteria). In this pilot study, we examined personality, somatic, and psychological variables with ethnically diverse samples of women with HG and women with typical levels of nausea and vomiting of pregnancy (NVP). Methods: Personality (Minnesota Multiphasic Personality Index-2 [MMPI-2] and MMPI-2RF), somatic (MMPI-2RF), and psychological (Beck Depression Inventory-II [BDI-II] and NVP-related quality of life) variables collected during the first trimester of pregnancy were compared between 15 women with HG and 15 women with normal levels of NVP matched for age, education, marital status, insurance source, and race/ethnicity. A secondary analysis was performed comparing these variables among a group of 9 asymptomatic pregnant women to the HG and NVP groups. Results: No significant differences were found between the HG and NVP groups on any personality, somatic, or psychological variables. Both groups had clinically significant elevations on the MMPI-2 hypochondriasis scale, which incorporates somatic symptoms. The NVP group had a clinically significant elevation on the MMPI-2RF gastrointestinal complaints scale. Both groups had significantly higher means on the MMPI-2 and MMPI-2RF scales than the asymptomatic group. Predominantly Spanish speakers appeared particularly vulnerable to psychological distress associated with somatic complaints. Conclusions: The results of this pilot study suggest that research with HG patients is feasible and that psychological distress expressed by women with HG and NVP may reflect reactions to somatic symptoms. No evidence was found to support an association between HG and personality characteristics. Recommendations for future research are provided, such as examining the potential benefits of translation services for Spanish-speaking HG patients. C1 [D'Orazio, Lina M.; Meyerowitz, Beth E.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Korst, Lisa M.; Goodwin, Thomas M.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, Detroit, MI USA. RP Meyerowitz, BE (reprint author), Univ So Calif, Dept Psychol, 3620 McClintock Ave,SGM 501, Los Angeles, CA 90089 USA. EM meyerow@usc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services [N01-HD-2-3342] FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services; contract number N01-HD-2-3342. NR 24 TC 7 Z9 8 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JAN PY 2011 VL 20 IS 1 BP 137 EP 144 DI 10.1089/jwh.2009.1851 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 709NH UT WOS:000286446900018 PM 21194308 ER PT J AU Le Couteur, DG Benson, VL McMahon, AC Blyth, F Handelsman, DJ Seibel, MJ Kennerson, M Naganathan, V Cumming, RG de Cabo, R AF Le Couteur, David G. Benson, Vicky L. McMahon, Aisling C. Blyth, Fiona Handelsman, David J. Seibel, Markus J. Kennerson, Marina Naganathan, Vasi Cumming, Robert G. de Cabo, Rafael TI Determinants of Serum-Induced SIRT1 Expression in Older Men: The CHAMP Study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE SIRT1 expression; Frailty ID CALORIE RESTRICTION; LIFE-SPAN; SURVIVAL; EXERCISE; FRAILTY; HEALTH; OBESITY; ADULTS; MICE AB Circulating factors that have an effect on SIRT1 expression are influenced by caloric restriction. To determine the association between frailty and such circulating factors, we measured serum-induced SIRT1 expression from a nested cohort of frail (n = 77) and robust (n = 82) participants from Concord Health and Ageing in Men Project, a population-based study of community-dwelling men older than 70 years. Serum-induced SIRT1 expression was not different between frail and robust men (103.1 +/- 17.0 versus 100.4 +/- 19.3 mu g/L). However, subsequent analyses showed that men with the lowest values (first quartile) were less likely to be frail (odds ratio = 0.5, 95% confidence interval = 0.2-1.0, p =.04) and had higher total body lean mass (p = .001) than the other participants. Serum-induced SIRT1 expression did not correlate with age, diseases, medications, albumin, fasting glucose, or lipids. Overall, there was no association between frailty and serum-induced SIRT1 expression; however, post hoc analysis suggested that there might be a paradoxical association between low serum-induced SIRT1 expression and robustness. C1 [Le Couteur, David G.; Benson, Vicky L.; McMahon, Aisling C.; Blyth, Fiona; Naganathan, Vasi; Cumming, Robert G.] Univ Sydney, Concord Repatriat Gen Hosp, Ctr Educ & Res Ageing, Concord, NSW 2139, Australia. [Le Couteur, David G.; Benson, Vicky L.; McMahon, Aisling C.; Blyth, Fiona; Handelsman, David J.; Seibel, Markus J.; Kennerson, Marina; Cumming, Robert G.] Concord Repatriat Gen Hosp, ANZAC Res Inst, Concord, NSW, Australia. [Cumming, Robert G.] Univ Sydney, Sch Publ Hlth, Concord, NSW 2139, Australia. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Le Couteur, DG (reprint author), Univ Sydney, Concord Repatriat Gen Hosp, Ctr Educ & Res Ageing, Hosp Rd, Concord, NSW 2139, Australia. EM david.lecouteur@sydney.edu.au RI Kennerson, Marina/B-5058-2014; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Benson, Victoria/0000-0002-9255-9025; , rafael/0000-0003-2830-5693 FU Australian National Health and Medical Research Council [512364]; Medical Foundation of the University of Sydney; Ageing and Alzheimer's Research Foundation FX This study was funded by the Australian National Health and Medical Research Council (grant 512364), the Medical Foundation of the University of Sydney, and the Ageing and Alzheimer's Research Foundation. NR 21 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2011 VL 66 IS 1 BP 3 EP 8 DI 10.1093/gerona/glq158 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 712GW UT WOS:000286655300001 PM 20819794 ER PT J AU Volpato, S Cavalieri, M Sioulis, F Guerra, G Maraldi, C Zuliani, G Fellin, R Guralnik, JM AF Volpato, Stefano Cavalieri, Margherita Sioulis, Fotini Guerra, Gianluca Maraldi, Cinzia Zuliani, Giovanni Fellin, Renato Guralnik, Jack M. TI Predictive Value of the Short Physical Performance Battery Following Hospitalization in Older Patients SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE SPPB; Hospitalization; Disability; Mortality; Prognosis ID LOWER-EXTREMITY PERFORMANCE; DENSITY-LIPOPROTEIN CHOLESTEROL; ILLNESS RATING-SCALE; BODY-COMPOSITION; WOMENS HEALTH; FUNCTIONAL TRAJECTORIES; SUBSEQUENT DISABILITY; MEDICAL ILLNESSES; NURSING-HOME; GAIT SPEED AB Background. Hospitalization represents a stressful and potentially hazardous event for older persons. We evaluated the value of the Short Physical Performance Battery (SPPB) in predicting rates of functional decline, rehospitalization, and death in older acutely ill patients in the year after discharge from the hospital. Methods. Prospective cohort study of 87 patients aged 65 years and older who were able to walk and with a Mini-Mental State Examination score >= 18 and admitted to the hospital with a clinical diagnosis of congestive heart failure, pneumonia, chronic obstructive pulmonary disease, or minor stroke. Patients were evaluated with the SPPB at hospital admission, were reevaluated the day of hospital discharge, and 1 month later. Subsequently, they were followed every 3 months by telephone interviews to ascertain functional decline, new hospitalizations, and vital status. Results. After adjustment for potential confounders, including self-report activity of daily living and comorbidity, the SPPB score at discharge was inversely correlated with the rate of decline in activity of daily living performance over the follow-up (p < .05). In a multivariable discrete-time survival analysis, patients with poor SPPB scores at hospital discharge (0-4) had a greater risk of rehospitalization or death (odds ratio: 5.38, 95% confidence interval: 1.82-15.9) compared with those with better SPPB scores (8-12). Patients with early decline in SPPB score after discharge also had steeper increase in activity of daily living difficulty and higher risk of rehospitalization or death over the next year. Conclusions. In older acutely ill patients who have been hospitalized, the SPPB provides important prognostic information. Lower extremity performance-based functional assessment might identify older patients at high risk of poor outcomes after hospital discharge. C1 [Volpato, Stefano; Cavalieri, Margherita; Sioulis, Fotini; Zuliani, Giovanni; Fellin, Renato] Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, I-44100 Ferrara, Italy. [Guerra, Gianluca] St Anna Hosp, Div Geriatr, Dept Med, Ferrara, Italy. [Maraldi, Cinzia] St Anna Hosp, Dept Med, Div Internal Med, Ferrara, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Volpato, S (reprint author), Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med Gerontol & Geriatr, Via Savonarola 9, I-44100 Ferrara, Italy. EM vlt@unife.it RI Cavalieri, Margherita/G-8053-2012; VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU National Institute on Aging, National Institutes of Health FX This research was supported in part by contracts from the National Institute on Aging, Intramural Research Program, National Institutes of Health. NR 39 TC 81 Z9 87 U1 4 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2011 VL 66 IS 1 BP 89 EP 96 DI 10.1093/gerona/glq167 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 712GW UT WOS:000286655300013 PM 20861145 ER PT J AU Rochon, J Bales, CW Ravussin, E Redman, LM Holloszy, JO Racette, SB Roberts, SB Das, SK Romashkan, S Galan, KM Hadley, EC Kraus, WE AF Rochon, James Bales, Connie W. Ravussin, Eric Redman, Leanne M. Holloszy, John O. Racette, Susan B. Roberts, Susan B. Das, Sai Krupa Romashkan, Sergei Galan, Katherine M. Hadley, Evan C. Kraus, William E. CA CALERIE Study Grp TI Design and Conduct of the CALERIE Study: Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Aging; Caloric restriction; Resting metabolic rate; Markers of inflammation; Randomized controlled trial ID DOUBLY-LABELED WATER; RANDOMIZED CONTROLLED-TRIAL; RESTING METABOLIC-RATE; LOW-CALORIE DIET; RHESUS-MONKEYS; BODY-COMPOSITION; PHYSICAL-ACTIVITY; CLINICAL-TRIALS; FOOD PROVISION; GLYCEMIC LOAD AB Background. In a robust and consistent manner, sustained caloric restriction (CR) has been shown to retard the aging process in a variety of animal species. Nonhuman primate studies suggest that CR may have similar effects in longer-lived species. The CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy) research program is the first systematic investigation of CR in nonobese human beings. In the phase 2 study, it is hypothesized that 2 years of sustained CR, involving a 25% reduction of ad libitum energy intake, results in beneficial effects similar to those observed in animal studies. This article presents the design and implementation of this study. Methods. The study is a multicenter, parallel-group, randomized controlled trial. A sample of 225 participants (22.0 <= body mass index [BMI] < 28.0 kg/m(2)) is being enrolled with 2: 1 allocation to CR. Results. An intensive dietary and behavioral intervention was developed to achieve 25% CR and sustain it over the 2 years. Adherence is monitored using a doubly labeled water technique. Primary outcomes are resting metabolic rate and core temperature, and are assessed at baseline and at 6-month intervals. Secondary outcomes address oxyradical formation, cardiovascular risk markers, insulin sensitivity and secretion, immune function, neuroendocrine function, quality of life and cognitive function. Biologic materials are stored in a central repository. Conclusions. An intricate protocol has been developed to conduct this study. Procedures have been implemented to safeguard the integrity of the data and the conclusions drawn. The results will provide insight into the detrimental changes associated with the human aging process and how CR mitigates these effects. C1 [Rochon, James; Bales, Connie W.; Galan, Katherine M.; Kraus, William E.] Duke Clin Res Inst, Durham, NC 27715 USA. [Rochon, James; Bales, Connie W.; Galan, Katherine M.; Kraus, William E.] Duke Univ, Med Ctr, Durham, NC USA. [Bales, Connie W.] VA Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. [Ravussin, Eric; Redman, Leanne M.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Holloszy, John O.; Racette, Susan B.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Roberts, Susan B.; Das, Sai Krupa] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Romashkan, Sergei; Hadley, Evan C.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. RP Rochon, J (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM james.rochon@duke.edu RI Biguzzi, Felipe/E-4724-2015; OI Racette, Susan/0000-0002-6932-1887; Kraus, William E/0000-0003-1930-9684 FU National Institute on Aging, National Institutes of Health [U01AG022132, U01AG020478, U01AG020487, U01AG020480] FX National Institute on Aging, National Institutes of Health (U01AG022132, U01AG020478, U01AG020487, and U01AG020480). NR 70 TC 55 Z9 57 U1 4 U2 21 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2011 VL 66 IS 1 BP 97 EP 108 DI 10.1093/gerona/glq168 PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 712GW UT WOS:000286655300014 PM 20923909 ER PT J AU Strand, BH Mishra, G Kuh, D Guralnik, JM Patel, KV AF Strand, Bjorn Heine Mishra, Gita Kuh, Diana Guralnik, Jack M. Patel, Kushang V. TI Smoking History and Physical Performance in Midlife: Results From the British 1946 Birth Cohort SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Physical performance; Aging; Smoking; Cigarette pack-years ID PERIPHERAL-NERVE FUNCTION; LUNG-FUNCTION; DEVELOPMENTAL ORIGINS; FATIGUE RESISTANCE; COGNITIVE DECLINE; GRIP STRENGTH; OLDER WOMEN; LIFE-COURSE; RISK-FACTOR; HEALTH AB Background. The adverse effects of smoking on individual medical conditions are well known; however, the cumulative effect of smoking on physical performance is not well characterized, particularly in midlife. Methods. In the British 1946 Birth Cohort Study, cigarette pack-years were examined with standing balance, chair rising, grip strength, and an overall composite index. Pack-years were calculated from data collected at ages 20, 25, 31, 36, 43, and 53 years, whereas physical performance, cognitive function, anthropometry, and spirometry were assessed at age 53 years in 2,394 men and women. Regression and cubic splines were used to assess the relationship between pack-years and physical performance. Results. Greater pack-years smoked were associated with lower overall physical performance and lower performance in standing balance and chair rising; however, there was no association with grip strength. For every 10 pack-years smoked, the overall physical performance index decreased by 0.11 SD (95% confidence interval: 0.07-0.15, p < .001), standing balance time decreased by 0.09 SD (0.05-0.13), and the reciprocal of chair rise time decreased by 0.11 SD (0.07-0.16). Adjustment for education, social class, lung function, cognitive function, and medical conditions attenuated the effect, but pack-years remained significantly associated with standing balance and chair rising time. Conclusions. Lifetime cigarette pack-years are strongly related to physical performance in the fifth decade of life, suggesting that smokers will enter older adulthood with decreased physiological reserve. As smoking prevalence remains high in many developed countries and is rapidly growing in developing countries, these findings underscore the need for effective smoking cessation and prevention programs. C1 [Strand, Bjorn Heine; Mishra, Gita; Kuh, Diana] MRC Unit Lifelong Hlth & Ageing, MRC Natl Survey Hlth & Dev, London, England. [Strand, Bjorn Heine; Guralnik, Jack M.; Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Strand, BH (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, NO-0403 Oslo, Norway. EM heine@fhi.no RI Mishra, Gita/F-8052-2011; OI Mishra, Gita/0000-0001-9610-5904; Strand, Bjorn/0000-0003-4385-8886 FU Medical Research Council Unit for Lifelong Health and Ageing in UK; National Institute on Aging, National Institutes of Health in USA; Research Council of Norway FX The manuscript is funded by Medical Research Council Unit for Lifelong Health and Ageing in UK and supported in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health in USA, and the Research Council of Norway. NR 29 TC 21 Z9 21 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2011 VL 66 IS 1 BP 142 EP 149 DI 10.1093/gerona/glq199 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 712GW UT WOS:000286655300020 PM 21071620 ER PT J AU Pattaradilokrat, S Li, J Su, XZ AF Pattaradilokrat, Sittiporn Li, Jian Su, Xin-zhuan TI Protocol for Production of a Genetic Cross of the Rodent Malaria Parasites SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Infectious Disease; Issue 47; Genetic cross; genetic mapping; malaria; rodent AB Variation in response to antimalarial drugs and in pathogenicity of malaria parasites is of biologic and medical importance. Linkage mapping has led to successful identification of genes or loci underlying various traits in malaria parasites of rodents(1-3) and humans(4-6). The malaria parasite Plasmodium yoelii is one of many malaria species isolated from wild African rodents and has been adapted to grow in laboratories. This species reproduces many of the biologic characteristics of the human malaria parasites; genetic markers such as microsatellite and amplified fragment length polymorphism (AFLP) markers have also been developed for the parasite(7-9). Thus, genetic studies in rodent malaria parasites can be performed to complement research on Plasmodium falciparum. Here, we demonstrate the techniques for producing a genetic cross in P. yoelii that were first pioneered by Drs. David Walliker, Richard Carter, and colleagues at the University of Edinburgh(10). Genetic crosses in P. yoelii and other rodent malaria parasites are conducted by infecting mice Mus musculus with an inoculum containing gametocytes of two genetically distinct clones that differ in phenotypes of interest and by allowing mosquitoes to feed on the infected mice 4 days after infection. The presence of male and female gametocytes in the mouse blood is microscopically confirmed before feeding. Within 48 hrs after feeding, in the midgut of the mosquito, the haploid gametocytes differentiate into male and female gametes, fertilize, and form a diploid zygote (Fig. 1). During development of a zygote into an ookinete, meiosis appears to occur(11). If the zygote is derived through cross-fertilization between gametes of the two genetically distinct parasites, genetic exchanges (chromosomal reassortment and cross-overs between the nonsister chromatids of a pair of homologous chromosomes; Fig. 2) may occur, resulting in recombination of genetic material at homologous loci. Each zygote undergoes two successive nuclear divisions, leading to four haploid nuclei. An ookinete further develops into an oocyst. Once the oocyst matures, thousands of sporozoites (the progeny of the cross) are formed and released into mosquito hemoceal. Sporozoites are harvested from the salivary glands and injected into a new murine host, where pre-erythrocytic and erythrocytic stage development takes place. Erythrocytic forms are cloned and classified with regard to the characters distinguishing the parental lines prior to genetic linkage mapping. Control infections of individual parental clones are performed in the same way as the production of a genetic cross. C1 [Pattaradilokrat, Sittiporn; Li, Jian; Su, Xin-zhuan] NIAID, NIH, Bethesda, MD USA. [Li, Jian] Xiamen Univ, Sch Life Sci, Xiamen, Peoples R China. RP Su, XZ (reprint author), NIAID, NIH, Bethesda, MD USA. EM xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; 973 National Basic Research Program of China [2007CB513103] FX We thank Drs Randy Elkins, Robin Kastenmayer, Ted Torrey, Dan Pare and Tovi Lehman for critical reading of manuscripts. This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by the 973 National Basic Research Program of China, #2007CB513103. We thank NIAID intramural editor Brenda Rae Marshall for assistance. NR 19 TC 1 Z9 1 U1 0 U2 0 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD JAN PY 2011 IS 47 AR UNSP e2365 DI 10.3791/2365 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36LF UT WOS:000209212800029 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. [Gipson, Chester] USDA, APHIS, AC, Washington, DC USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2011 VL 40 IS 1 BP 12 EP 12 DI 10.1038/laban0111-12a PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 700KM UT WOS:000285737700017 PM 21173767 ER PT J AU Balsam, J Ossandon, M Kostov, Y Bruck, HA Rasooly, A AF Balsam, Joshua Ossandon, Miguel Kostov, Yordan Bruck, Hugh Alan Rasooly, Avraham TI Lensless CCD-based fluorometer using a micromachined optical Soller collimator SO LAB ON A CHIP LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; ON-CHIP MICROSCOPY; BOTULINUM NEUROTOXIN; NEUROTRANSMITTER RELEASE; OPTOFLUIDIC MICROSCOPY; CAENORHABDITIS-ELEGANS; PROTEOLYTIC CLEAVAGE; CARBON NANOTUBES; ARRAY BIOSENSOR; PROTEIN AB In this paper, we describe a simple charge-coupled device (CCD) based lensless fluorometer with sensitivity in the range of current ELISA plate readers. In our lensfree fluorometer, a multi-wavelength LED light source was used for fluorophore excitation. To collimate the light, we developed a simple optical Soller collimator based on a "stack of pinholes'' (a stack of black PMMA with array of pinholes machined with laser) enabling the light to be collimated from the LED through the filters and the assay's microfluidics directly onto the CCD without a lens. The elimination of the lens that is used in almost all other current CCD based detection systems has four major advantages: (1) It simplifies the device design and fabrication while reducing cost. (2) It reduces the distance between the sample and the measuring device (without a lens the distance needed to focus the image on the CCD is reduced and the fluorometer can be more compact). (3) It couples the CCD and the detected surface by using an optical Soller Collimator which allows the use of filters for fluorescence detection. (4) It also uncouples the CCD and the microfluidics to enable the use of interchangeable fluidics while protecting the delicate CCD. The lensless CCD-based fluorometer is capable of detecting 16 samples simultaneously, and was used for in vitro detection of botulinum neurotoxin serotype A (BoNT-A) activity with a FRET assay that measures cleavage of a fluorophore-tagged peptide substrate specific for BoNT-A (SNAP-25) by the toxin light chain (LcA). The limit of detection (LOD) of our lensless fluorometer is 1.25 nM, which is similar to the LOD of a modern ELISA plate reader. Combined with microfluidics, this simple low cost point-of-care (POC) medical diagnostic system may be useful for the performance of many other complex medical diagnostic assays without a laboratory and thus potentially enhancing the accessibility and the quality of health care delivery in underserved populations. C1 [Balsam, Joshua; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Balsam, Joshua; Bruck, Hugh Alan] UMCP, College Pk, MD 20742 USA. [Ossandon, Miguel; Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, NIH, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov NR 52 TC 22 Z9 22 U1 3 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 5 BP 941 EP 949 DI 10.1039/c0lc00431f PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 722CW UT WOS:000287409600023 PM 21243150 ER PT J AU Nguyen, CQ Yin, HE Lee, BH Chiorini, JA Peck, AB AF Nguyen, Cuong Q. Yin, Hongen Lee, Byung Ha Chiorini, John A. Peck, Ammon B. TI IL17: potential therapeutic target in Sjogren's syndrome using adenovirus-mediated gene transfer SO LABORATORY INVESTIGATION LA English DT Article DE adenoviral vector; gene therapy; IL17; IL17R; Sjogren's syndrome; T(H)17 cells ID T-HELPER-CELLS; SALIVARY-GLANDS; TRANSFER VECTORS; LOCAL-DELIVERY; B-LYMPHOCYTES; MURINE MODEL; TGF-BETA; MICE; DISEASE; INTERLEUKIN-17 AB Sjogren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears that eventually result in dry mouth and dry eye diseases. T(H)17 cell populations secreting IL17A have been shown to have an important function in an increasing number of autoimmune diseases, including SS. In this study, we investigated the function of IL17A on SS development and onset. Adenovirus-5 vectors expressing either IL17R:fragment of crystallization (Fc) fusion protein or LacZ were injected through retrograde cannulation into the salivary glands of SS-susceptible (SS(S)) C57BL/6.NOD-Aec1Aec2 mice between 6 and 8 weeks of age (a pre-disease stage) or 15 and 17 weeks of age (a diseased stage). The mice were subsequently characterized for their SS phenotypes. Mice cannulated with the Ad5-IL17R:Fc viral vector at either 7 or 16 weeks of age exhibited a rapid temporal, yet persistent, decrease in the levels of serum IL17 as well as the overall numbers of CD4 vertical bar IL17 vertical bar T cells present in their spleens. Disease profiling indicated that these mice showed decreased lymphocytic infiltrations of their salivary glands, normalization of their antinuclear antibodies repertoire, and increased saliva secretion. In contrast, mice cannulated with the control Ad5-LacZ viral vector did not exhibit similar changes and progressed to the overt disease stage. The capacity of the Ad5-IL17R: Fc-blocking factor to reduce SS pathology in SS(S) mice strongly suggests that IL17 is an important inflammatory cytokine in salivary gland dysfunction. Thus, therapeutic approach targeting IL17 may be effective in preventing glandular dysfunction. Laboratory Investigation (2011) 91, 54-62; doi:10.1038/labinvest.2010.164; published online 20 September 2010 C1 [Nguyen, Cuong Q.; Lee, Byung Ha; Peck, Ammon B.] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. [Nguyen, Cuong Q.; Peck, Ammon B.] Univ Florida, Coll Dent, Ctr Orphan Autoimmune Disorders, Gainesville, FL 32610 USA. [Yin, Hongen; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Peck, Ammon B.] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. RP Nguyen, CQ (reprint author), Univ Florida, Coll Dent, Dept Oral Biol, POB 100424, Gainesville, FL 32610 USA. EM Nguyen@pathology.ufl.edu FU NIDCR [K99 DE018958]; NIAID [1R21AI081952]; NIH FX We thank Dr Jay K Kolls and Dr Julie Bindas (Children's Hospital of Pittsburgh) for generously providing the Ad5-LacZ and Ad5-IL17R:Fc vectors, and Dr Phil Cohen for his critical reading of the manuscript and helpful suggestions. We greatly appreciate the assistance of Dr Craig Meyers and Dr Nicholas Muzyczka for the use of the microscope. This work was supported by PHS Grant K99 DE018958 grant (CQN) from the NIDCR. ABP and CQN were supported by PHS Grant 1R21AI081952 from NIAID. HY and JAC were supported by an NIH, NIDCR intramural research grant. NR 44 TC 29 Z9 32 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2011 VL 91 IS 1 BP 54 EP 62 DI 10.1038/labinvest.2010.164 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 699WW UT WOS:000285694600006 PM 20856230 ER PT J AU Ozaki, T Nagashima, K Kusakabe, T Kakudo, K Kimura, S AF Ozaki, Takashi Nagashima, Kunio Kusakabe, Takashi Kakudo, Kennichi Kimura, Shioko TI Development of thyroid gland and ultimobranchial body cyst is independent of p63 SO LABORATORY INVESTIGATION LA English DT Article DE electron microscopy; histochemical analysis; knockout mouse; NKX2-1; solid cell nest; undifferentiated cells ID SOLID CELL NESTS; ENHANCER-BINDING PROTEIN; STEM-CELL; C-CELLS; MUCOEPIDERMOID CARCINOMA; HASHIMOTOS-THYROIDITIS; EPITHELIAL-CELL; FACTOR-I; EXPRESSION; ORIGIN AB The ultimobranchial body (UBB) and thyroid primordium are the origins of the thyroid gland that fuse around embryonic day 14.5 of mouse gestation, ultimately giving rise to calcitonin-producing C cells and thyroglobulin-producing follicular cells, respectively. A homeodomain transcription factor NKX2-1 is expressed both in the UBB and the thyroid primordium, and is critical for development of the thyroid gland. In this study, the role of p63 in development of UBB and the thyroid gland was analyzed by histological, immunohistochemical, and electron microscopic analyses using mice with various combinations of Nkx2-1 and p63 wild-type, heterozygous, and null alleles. In the absence of p63, a normal thyroid gland develops, as revealed by expression of thyroglobulin and calcitonin, thus showing that p63 is not required for thyroid development. However, in mice carrying the Nkx2-1-null allele, the UBB remains as a cystic vesicular structure and/or in nested patterns consisting of p63-positive cells surrounding the vesicle and undifferentiated immature cells with occasional cilia lying inside. The cystic UBB was present even in the Nkx2-1; p63 double-null mice. The structure and p63 expression pattern of the UBB cyst strikingly resemble the solid cell nest. These results show that in the absence of NKX2-1, UBB becomes cystic independent of p63, which is likely the origin of SCN. Laboratory Investigation (2011) 91, 138-146; doi:10.1038/labinvest.2010.137; published online 9 August 2010 C1 [Ozaki, Takashi; Kusakabe, Takashi; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Ozaki, Takashi; Kakudo, Kennichi] Wakayama Med Univ, Dept Pathol, Wakayama, Japan. [Nagashima, Kunio] NCI Frederick, Electron Microscopy Facil, Adv Technol Program, SAIC Frederick, Frederick, MD USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov FU National Cancer Institute, Center for Cancer Research FX We thank Drs Alea Mills (Cold Spring Harbor Laboratory) for providing us p63(fl/fl) mice and Frank Gonzalez (NCI) for his critical review of the paper. This work was supported by Intramural Research Program of the National Cancer Institute, Center for Cancer Research. NR 47 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2011 VL 91 IS 1 BP 138 EP 146 DI 10.1038/labinvest.2010.137 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 699WW UT WOS:000285694600012 PM 20697379 ER PT J AU Blackstone, C AF Blackstone, Craig TI Infantile parkinsonism-dystonia due to dopamine transporter gene mutations: another genetic twist SO LANCET NEUROLOGY LA English DT Editorial Material C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD JAN PY 2011 VL 10 IS 1 BP 24 EP 25 DI 10.1016/S1474-4422(10)70280-5 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 701HX UT WOS:000285810100014 PM 21112252 ER PT S AU Tangrea, MA Hanson, JC Bonner, RF Pohida, TJ Rodriguez-Canales, J Emmert-Buck, MR AF Tangrea, Michael A. Hanson, Jeffrey C. Bonner, Robert F. Pohida, Thomas J. Rodriguez-Canales, Jaime Emmert-Buck, Michael R. BE Murray, GI TI Immunoguided Microdissection Techniques SO LASER CAPTURE MICRODISSECTION: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Automation; Immunohistochemistry; Microdissection ID LASER CAPTURE MICRODISSECTION; PARAFFIN-EMBEDDED TISSUES; MESSENGER-RNA ANALYSIS; IMMUNOHISTOCHEMICAL DEMONSTRATION; PROMOTER METHYLATION; MOLECULAR ANALYSIS; ANTIGEN RETRIEVAL; PROSTATE-CANCER; IN-SITU; FORMALIN AB Over the past 15 years, laser-based microdissection has improved the precision by which scientists can procure cells of interest from a heterogeneous tissue section. However, for studies that require a large amount of material (e.g., proteomics) or for cells that are scattered and difficult to identify, by standard histological stains, an immunostain-based, automated approach becomes essential. In this chapter, we discuss the use of immunohistochemistry (IHC) and immunofluorescence (IF) to guide the microdissection process via manual and software-driven auto-dissection methods. Although technical challenges still exist with these innovative approaches, we present here methods and protocols to successfully perform imnmno-based microdissection on commercially available laser dissection systems. C1 [Tangrea, Michael A.; Hanson, Jeffrey C.; Bonner, Robert F.; Pohida, Thomas J.; Rodriguez-Canales, Jaime] NIH, Pathogenet Unit, Bethesda, MD 20892 USA. [Tangrea, Michael A.; Hanson, Jeffrey C.; Bonner, Robert F.; Pohida, Thomas J.; Rodriguez-Canales, Jaime] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Emmert-Buck, Michael R.] Ctr Canc Res, Pathogenet Unit, Gaithersburg, MD USA. [Emmert-Buck, Michael R.] Ctr Canc Res, Laser Microdissect Core, Pathol Lab, Gaithersburg, MD USA. RP Tangrea, MA (reprint author), NIH, Pathogenet Unit, Bldg 10, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015; OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU Intramural NIH HHS [ZIA HD000265-13] NR 28 TC 4 Z9 4 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-162-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 755 BP 57 EP 66 DI 10.1007/978-1-61779-163-5_4 D2 10.1007/978-1-61779-163-5 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BWE67 UT WOS:000293771800004 PM 21761293 ER PT S AU Johann, DJ Mukherjee, S Prieto, DA Veenstra, TD Blonder, J AF Johann, Donald J. Mukherjee, Sumana Prieto, DaRue A. Veenstra, Timothy D. Blonder, Josip BE Murray, GI TI Profiling Solid Tumor Heterogeneity by LCM and Biological MS of Fresh-Frozen Tissue Sections SO LASER CAPTURE MICRODISSECTION: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Thin fresh-frozen tissue sections; Laser capture microdissection; Liquid chromatography-mass spectrometry; Solid tumor heterogeneity; Biomarker; Cancer ID LASER CAPTURE MICRODISSECTION; MASS-SPECTROMETRY; PROTEOMICS; CANCER AB The heterogeneous nature of solid tumors represents a common problem in mass spectrometry (MS)-based analysis of fresh-frozen tissue specimens. Here, we describe a method that relies on synergy between laser capture microdissection (LCM) and MS for enhanced molecular profiling of solid tumors. This method involves dissection of homogeneous histologic cell types from thin fresh-frozen tissue sections via LCM, coupled with liquid chromatography (LC)-MS analysis. Such an approach enables an in-depth molecular profiling of captured cells. This is a bottom-up proteomic approach, where proteins are identified through peptide sequencing and matching against a specific proteomic database. Sample losses are minimized, since lysis, solubilization, and digestion are carried out directly on LCM caps in buffered methanol using a single tube, thus reducing sample loss between these steps. The rationale for the LCM-MS coupling is that once the optimal method parameters are established for a solid tumor of interest, homogeneous histologic tumor/tissue cells (i.e., tumor proper, stroma, etc.) can be effectively studied for potential biomarkers, drug targets, pathway analysis, as well as enhanced understanding of the pathological process under study. C1 [Johann, Donald J.; Mukherjee, Sumana] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Prieto, DaRue A.; Veenstra, Timothy D.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Johann, DJ (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. FU PHS HHS [HSN261200800001E] NR 10 TC 7 Z9 7 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-162-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 755 BP 95 EP 106 DI 10.1007/978-1-61779-163-5_8 D2 10.1007/978-1-61779-163-5 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BWE67 UT WOS:000293771800008 PM 21761297 ER PT J AU Williams, ME Connors, JM Dreyling, MH Gascoyne, RD Kahl, BS Leonard, JP Press, OW Wilson, WH AF Williams, Michael E. Connors, Joseph M. Dreyling, Martin H. Gascoyne, Randy D. Kahl, Brad S. Leonard, John P. Press, Oliver W. Wilson, Wyndham H. TI Mantle cell lymphoma: report of the 2010 Mantle Cell Lymphoma Consortium Workshop SO LEUKEMIA & LYMPHOMA LA English DT Review DE Mantle cell lymphoma; MicroRNA; Minimal residual disease (MRD); Cell cycle; Immunotherapy; Adoptive cellular therapy ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; CENTROCYTIC LYMPHOMA; DNA METHYLATION; EXPRESSION; SURVIVAL; CLADRIBINE; GENES; PROLIFERATION; PROGRESSION AB Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma typically characterized by cyclin D1 overexpression as result of the t(11;14) translocation. MCL is biologically and clinically heterogeneous and frequently involves extranodal dissemination. Although MCL is incurable with current therapies, with the exception of allogeneic stem cell transplant, recent advances are improving long-term outcomes in MCL. Intensive research has continued to focus on elucidating biological mechanisms of MCL, identifying new molecular targets, and optimizing existing therapies. Most recently, researchers have begun focusing on new areas such as epigenetics and microRNAs and their potential applications to MCL therapy. Advances across a broad spectrum of MCL research were presented at a recent MCL Workshop. This report provides an overview of the scientific highlights from the meeting and a framework for future research. C1 [Williams, Michael E.] Univ Virginia, Sch Med, Div Hematol Oncol, Charlottesville, VA 22908 USA. [Connors, Joseph M.; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Dreyling, Martin H.] Univ Hosp Munich Grosshadern, Munich, Germany. [Kahl, Brad S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Leonard, John P.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Press, Oliver W.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. RP Williams, ME (reprint author), Univ Virginia, Sch Med, Div Hematol Oncol, Box 800716,Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM mew4p@virginia.edu FU LRF FX Meeting support was provided by the LRF and by Millennium: The Takeda Oncology Company. All co-authors are members of the LRF Scientific Advisory Board. Work summarized in this report has been supported in part by LRF Mantle Cell Lymphoma Initiative and Correlative grants. NR 49 TC 10 Z9 10 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2011 VL 52 IS 1 BP 24 EP 33 DI 10.3109/10428194.2010.532893 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 715RM UT WOS:000286901600007 PM 21133727 ER PT J AU Smith, BD Jones, RJ Cho, EP Kowalski, J Karp, JE Gore, SD Vala, M Meade, B Baker, SD Zhao, M Piantadosi, S Zhang, Z Blumenthal, G Warlick, ED Brodsky, RA Murgo, A Rudek, MA Matsui, WH AF Smith, B. Douglas Jones, Richard J. Cho, Eunpi Kowalski, Jeanne Karp, Judith E. Gore, Steven D. Vala, Milada Meade, Brooke Baker, Sharyn D. Zhao, Ming Piantadosi, Steven Zhang, Zhe Blumenthal, Gideon Warlick, Erica D. Brodsky, Robert A. Murgo, Anthony Rudek, Michelle A. Matsui, William H. TI Differentiation therapy in poor risk myeloid malignancies: Results of a dose finding study of the combination bryostatin-1 and GM-CSF SO LEUKEMIA RESEARCH LA English DT Article DE Leukemia; Differentiation therapy; Myelodysplastic syndrome; Growth factors; Bryostatin; Drug resistance ID CONTINUAL REASSESSMENT METHOD; ACUTE PROMYELOCYTIC LEUKEMIA; INTERNATIONAL WORKING GROUP; PROTEIN-KINASE-C; AGENT BRYOSTATIN-1; RESPONSE CRITERIA; GROWTH-FACTORS; CELLS; TRIALS; ASSAY AB Purpose: Pharmacologic differentiating agents have had relatively limited clinical success outside of the use of ATRA in acute promyelocytic leukemia and DNA methyltransferase inhibitors in myelodysplastic syndromes. The differentiating effects of such agents can be enhanced in combination with lineage-specific growth factors. We developed a dose finding trial to assess toxicity, differentiating activity, and clinical impact of the combination of bryostatin-1 and GM-CSF. Experimental design: Patients with poor risk myeloid malignancies were eligible to enroll in a dose finding study of continuous infusion bryostatin-1 combined with a fixed dose of daily GM-CSF. Toxicities were graded per NCI CTC version 2.0 and pharmacokinetic and correlative study samples were obtained to assess the combination's clinical and biologic differentiating effects. Results: Thirty-two patients were treated with the combination therapy and the dose determined to be most suitable for study in a larger trial was continuous infusion broystatin-1 at 16 mu g/m(2) for 14 days and subcutaneous GM-CSF at 125 mu g/m(2) daily for 14 days every 28 days. Arthralgias and myalgias limited further dose escalation. Clinically, the combination impacted differentiation with improvement of absolute neutrophil counts (p = 0.0001) in the majority of patients. Interestingly, there were two objective clinical responses, including a CR after a single cycle. Both the bryostatin-1 plasma concentrations and the correlative studies supported biologic activity of the combination at the doses where clinical responses were observed. Conclusions: Combining growth factors with pharmacologic differentiating agents may increase their clinical effectiveness and further studies should focus on such combinations. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Smith, B. Douglas; Jones, Richard J.; Cho, Eunpi; Kowalski, Jeanne; Karp, Judith E.; Gore, Steven D.; Vala, Milada; Meade, Brooke; Zhao, Ming; Zhang, Zhe; Brodsky, Robert A.; Rudek, Michelle A.; Matsui, William H.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Baker, Sharyn D.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Piantadosi, Steven] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Blumenthal, Gideon; Murgo, Anthony] NIH, Washington, DC USA. [Warlick, Erica D.] Univ Minnesota, Minneapolis, MN USA. RP Smith, BD (reprint author), Johns Hopkins Med Inst, Sidney Kimmel Canc Ctr Johns Hopkins, 1650 Orleans St,Room 246 CRB1, Baltimore, MD 21287 USA. EM bdsmith@jhmi.edu OI Matsui, William/0000-0002-3088-0964 FU Johns Hopkins [U01CA70095, BMT P01CA15396]; NIH CCSG [P30CA069773]; Leukemia/Lymphoma Society [6094-10] FX This work was supported by Johns Hopkins U01CA70095, NIH CCSG P30CA069773 and Johns Hopkins BMT P01CA15396, and Leukemia/Lymphoma Society Grant #6094-10. We would like to thank Ping He, Karina Holland, and Jeffrey Sivik for their technical support; Susan Davidson for quality assurance of the data contained in this manuscript and Robin Carlson for her assistance with the final manuscript preparation. NR 30 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2011 VL 35 IS 1 BP 87 EP 94 DI 10.1016/j.leukres.2010.06.001 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 695YR UT WOS:000285409400027 PM 20598742 ER PT B AU Yong, ASM Melo, JV AF Yong, Agnes S. M. Melo, Junia V. BE Faderl, S Kantarjian, H TI Pathophysiology of Chronic Myeloid Leukemia SO LEUKEMIAS: PRINCIPLES AND PRACTICE OF THERAPY LA English DT Article; Book Chapter ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; COLONY-STIMULATING FACTOR; CHRONIC GRANULOCYTIC-LEUKEMIA; DERIVATIVE CHROMOSOME-9 DELETIONS; IMATINIB MESYLATE THERAPY; STEM-CELL TRANSPLANTATION; CYTOTOXIC T-LYMPHOCYTES; BLAST-CRISIS CML; BCR-ABL C1 [Yong, Agnes S. M.] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Melo, Junia V.] Univ Adelaide, Ctr Canc Biol SA Pathol, Adelaide, SA, Australia. RP Yong, ASM (reprint author), NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA. NR 126 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-4443-2736-6; 978-1-4051-8235-5 PY 2011 BP 261 EP 270 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA BA6GJ UT WOS:000337135300022 ER PT S AU Bienstock, RJ AF Bienstock, Rachelle J. BE Bienstock, RJ TI Overview: Fragment-Based Drug Design SO LIBRARY DESIGN, SEARCH METHODS, AND APPLICATIONS OF FRAGMENT-BASED DRUG DESIGN SE ACS Symposium Series LA English DT Editorial Material; Book Chapter ID X-RAY CRYSTALLOGRAPHY; NOVO LIGAND DESIGN; BETA-SECRETASE; COMBINATORIAL CHEMISTRY; MOLECULAR FRAGMENTS; KINASE INHIBITOR; LEAD GENERATION; ELECTROSTATIC SOLVATION; ORGANIC-MOLECULES; LIBRARY DESIGN AB Fragment-based drug design has recently risen to great prominence as a new methodology for novel lead identification: This chapter is a general overview of computational methods for all three phases of fragment-based ligand design: (1) Designing and Searching Fragment Libraries, (2) Computational Screening: Docking, and (3) Leads from Fragments: Fragment Growing and Linking. Appendix 1 at the end of this chapter summarizes a large number of computational methods and software programs available with associated web sites and references. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Bienstock, RJ (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 68 TC 1 Z9 2 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2492-6 J9 ACS SYM SER JI ACS Symp. Ser. PY 2011 VL 1076 BP 1 EP 26 D2 10.1021/bk-2011-1076 PG 26 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Pharmacology & Pharmacy SC Computer Science; Pharmacology & Pharmacy GA BB6DX UT WOS:000344713500001 ER PT J AU Kim, S Chen, MH Dey, DK AF Kim, Sungduk Chen, Ming-Hui Dey, Dipak K. TI A new threshold regression model for survival data with a cure fraction SO LIFETIME DATA ANALYSIS LA English DT Article DE Cure rate models; DIC; Latent variables; LPML; Markov chain Monte Carlo; Posterior distribution; Prostate cancer ID LONG-TERM SURVIVORS; PROPORTIONAL HAZARDS; MIXTURE-MODELS; TRANSFORMATION MODELS; RISK AB Due to the fact that certain fraction of the population suffering a particular type of disease get cured because of advanced medical treatment and health care system, we develop a general class of models to incorporate a cure fraction by introducing the latent number N of metastatic-competent tumor cells or infected cells caused by bacteria or viral infection and the latent antibody level R of immune system. Various properties of the proposed models are carefully examined and a Markov chain Monte Carlo sampling algorithm is developed for carrying out Bayesian computation for model fitting and comparison. A real data set from a prostate cancer clinical trial is analyzed in detail to demonstrate the proposed methodology. C1 [Chen, Ming-Hui; Dey, Dipak K.] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Kim, Sungduk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. RP Chen, MH (reprint author), Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. EM kims2@mail.nih.gov; mhchen@stat.uconn.edu; dipak.dey@uconn.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH [GM 70335, CA 74015] FX The authors wish to thank the guest editor, Paul Gustafson, and the referee for helpful comments and suggestions, which have led to an improvement of this article. Dr. Kim is supported by the Intramural research program of National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Chen's research was partially supported by NIH grants #GM 70335 and #CA 74015. NR 42 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD JAN PY 2011 VL 17 IS 1 BP 101 EP 122 DI 10.1007/s10985-010-9166-9 PG 22 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 706FD UT WOS:000286202400011 PM 20414804 ER PT J AU Kurotani, R Kumaki, N Xu, NZ Ward, JM Linnoila, RI Kimura, S AF Kurotani, Reiko Kumaki, Nobue Xu Naizhen Ward, Jerrold M. Linnoila, R. Ilona Kimura, Shioko TI Secretoglobin 3A2/uteroglobin-related protein 1 is a novel marker for pulmonary carcinoma in mice and humans SO LUNG CANCER LA English DT Article DE SCGB3A2; UGRP1; NKX2-1; TTF1; NSCLC; Aging B6;129 mice; CC10TAg transgenic mice; Pulmonary carcinoma; Carcinoma marker; Histopathological and immunohistochemical analysis ID TRANSCRIPTION FACTOR-I; CELL-SPECIFIC EXPRESSION; TRANSGENIC MICE; LUNG DEVELOPMENT; MORPHOMETRIC-ANALYSIS; BINDING-PROTEIN; GENE-EXPRESSION; 10-KDA PROTEIN; CANCER-CELLS; MOUSE LUNG AB Secretoglobin (SCGB) 3A2, also called uteroglobin-related protein (UGRP) 1, is a downstream target for a homeodomain transcription factor NKX2-1, which is critical for the development of lung, thyroid and ventral forebrain. Both SCGB3A2 and NKX2-1 are expressed in airway epithelial cells and the latter also in alveolar Type II cells. NKX2-1 has been used clinically for diagnosis of human pulmonary tumors. Recently, the expression of SCGB3A2 was reported in human carcinomas, suggesting the use of this protein as a tumor marker. In this study, 28 lung tumors from aging B6;129 mice and nine lung adenocarcinomas from CC10TAg transgenic mice that express SV40 large T antigen under the mouse Scgb1a1 (CC10) gene promoter, were subjected to histopathological and immunohistochemical analyses for the expression of NKX2-1 and SCGB3A2. NKX2-1 was expressed in all types of tumors albeit more focally in carcinomas. In contrast, SCGB3A2 normally expressed in Clara cells, was negative in Type II cell hyperplasias and adenomas. However, it was expressed in alveolar Type II cell carcinomas and Clara cell adenocarcinomas. In these carcinomas, SCGB3A2 expression was observed in the portion of the tumor where NKX2-1 expression was reduced or almost abolished. As a comparison, the expression of SCGB3A2 and NKX2-1 from 23 human non-small cell lung carcinoma specimens was also examined. The results demonstrate that SCGB3A2 is a useful marker for diagnosis of pulmonary tumors both in mice and humans. Published by Elsevier Ireland Ltd. C1 [Kurotani, Reiko; Kimura, Shioko] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kurotani, Reiko] Yokohama City Univ, Grad Sch Med, Cardiovasc Res Inst, Yokohama, Kanagawa 2360004, Japan. [Kumaki, Nobue] Tokai Univ, Sch Med, Dept Pathol, Kanagawa 2591193, Japan. [Xu Naizhen; Linnoila, R. Ilona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD 20886 USA. RP Kimura, S (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov FU National Cancer Institute, Center for Cancer Research; Yokohama Foundation for Advancement of Medical Science FX This study was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research (S.K.), and by Yokohama Foundation for Advancement of Medical Science (R.K.). NR 53 TC 8 Z9 10 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JAN PY 2011 VL 71 IS 1 BP 42 EP 48 DI 10.1016/j.lungcan.2010.04.001 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 710TS UT WOS:000286540500007 PM 20466451 ER PT B AU Adhya, S AF Adhya, Sankar BE Maloy, S Hughes, KT Casadesus, J TI WHY GALACTOSE? THE EARLY CURIOSITIES AND THE CONSEQUENCES SO LURE OF BACTERIAL GENETICS: A TRIBUTE TO JOHN ROTH LA English DT Article; Book Chapter ID BIOSYNTHESE DES ENZYMES; ESCHERICHIA COLI K12; RNA-POLYMERASE; GAL OPERON; TRANSCRIPTION TERMINATION; CYCLIC-AMP; RECEPTOR PROTEIN; BACTERIOPHAGE-LAMBDA; TRANSPORT SYSTEMS; MESSENGER-RNA C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 68 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 978-1-55581-538-7 PY 2011 BP 43 EP 53 PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA BSL44 UT WOS:000284857100006 ER PT J AU Satria, MN Pacheco-Rodriguez, G Moss, J AF Satria, Melissa N. Pacheco-Rodriguez, Gustavo Moss, Joel TI Pulmonary Lymphangiomatosis SO LYMPHATIC RESEARCH AND BIOLOGY LA English DT Article ID THORACIC LYMPHANGIOMATOSIS; DIFFUSE LYMPHANGIOMATOSIS; DISEASE; LYMPHANGIOLEIOMYOMATOSIS; LYMPHOSCINTIGRAPHY; COAGULATION; CHYLOTHORAX; SPECTRUM; THERAPY; MARKERS AB Lymphangiomatosis is a rare disease characterized by diffuse infiltration of lymphangiomas in the lung, bone, and other tissues. Due to its rarity, the spectrum of lymphangiomatosis is beginning to be elucidated based on case reports. The limited pathological, radiological, and clinical studies have shed light on this disease. Treatments have been tested in unblinded manner with promising results; however, further understanding of the pathogenesis of disease, as well as its natural history, is needed to facilitate drug development. C1 [Satria, Melissa N.; Pacheco-Rodriguez, Gustavo; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU National Institutes of Health/National Heart, Lung, and Blood Institute FX This research was funded by the Intramural Research Program of the National Institutes of Health/National Heart, Lung, and Blood Institute. NR 25 TC 9 Z9 9 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1539-6851 J9 LYMPHAT RES BIOL JI Lymphat. Res. Biol. PY 2011 VL 9 IS 4 BP 191 EP 193 DI 10.1089/lrb.2011.0023 PG 3 WC Medicine, Research & Experimental; Physiology SC Research & Experimental Medicine; Physiology GA 875CZ UT WOS:000299009200004 PM 22196284 ER PT J AU Shmueli, K Dodd, SJ Li, TQ Duyn, JH AF Shmueli, Karin Dodd, Stephen J. Li, Tie-Qiang Duyn, Jeff H. TI The Contribution of Chemical Exchange to MRI Frequency Shifts in Brain Tissue SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI phase contrast; resonance frequency shift; proton chemical exchange; exchange-induced frequency shift ID WHITE-MATTER CONTRAST; GRADIENT-ECHO MRI; HIGH-FIELD MRI; PHASE-CONTRAST; IN-VIVO; MAGNETIC-SUSCEPTIBILITY; INTERNAL REFERENCES; IRON CONTENT; PROTEINS; IMAGES AB Recent high-field MRI studies based on resonance frequency contrast have revealed brain structure with unprecedented detail. Although subtle magnetic susceptibility variations caused by iron and myelin seem to be important to this contrast, recent research on protein solutions suggests that chemical exchange between water and macromolecular protons may contribute substantially to the observed gray-white matter frequency contrast. To investigate this, we performed spectroscopic MRI experiments at 14 T on samples of fixed human visual cortex and fresh pig brain. To allow direct observation of any exchange-induced frequency shifts, these samples were soaked in reference chemicals (TSP and dioxane) that are assumed not to be involved in exchange. For both fresh and fixed tissues and with both reference chemicals, substantial negative exchange-induced gray-white matter frequency contrast (-6.3 to -13.5 ppb) was found, whereas intracortical contrast was negligible. The sign of the gray-white matter exchange-induced frequency difference was opposite to the overall gray-white matter frequency difference observed in vivo. This suggests that exchange contributes to, but is not sufficient to explain, the frequency contrast in vivo and tissue susceptibility differences may have a greater contribution than previously thought. The exchange-dependent contribution may report on tissue chemical composition and pH. Magn Reson Med 65:35-43, 2011. (c) 2010 Wiley-Liss, Inc. C1 [Shmueli, Karin; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. [Dodd, Stephen J.] Natl Inst Neurol Disorders & Stroke, Funct & Mol Metab Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. [Li, Tie-Qiang] Karolinska Univ Hosp, Huddinge MR Res Ctr, Dept Med Phys, Stockholm, Sweden. RP Shmueli, K (reprint author), 10 Ctr Dr,Bldg 10,Room B1D728, Bethesda, MD 20892 USA. EM shmuelik@mail.nih.gov RI Shmueli, Karin/B-9432-2017; OI Li, Tieqiang/0000-0002-6636-8938; Li, Tie-Qiang/0000-0002-4866-5904 FU National Institute for Neurological Disorders and Stroke, National Institutes of Health FX Grant sponsors: National Institute for Neurological Disorders and Stroke, National Institutes of Health (Intramural Research Program). NR 46 TC 35 Z9 35 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2011 VL 65 IS 1 BP 35 EP 43 DI 10.1002/mrm.22604 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703FM UT WOS:000285963500005 PM 20928888 ER PT J AU Sampath, S Derbyshire, JA Ledesma-Carbayo, MJ McVeigh, ER AF Sampath, Smita Derbyshire, John Andrew Ledesma-Carbayo, Maria J. McVeigh, Elliot R. TI Imaging Left Ventricular Tissue Mechanics and Hemodynamics During Supine Bicycle Exercise Using a Combined Tagging and Phase-Contrast MRI Pulse Sequence SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE bicycle exercise; stress; tagging; phase-contrast; SPAMM ID CORONARY-ARTERY-DISEASE; MITRAL REGURGITATION; MYOCARDIAL-FUNCTION; MAGNETIC-RESONANCE; STRESS ECHOCARDIOGRAPHY; SPATIAL MODULATION; MOTION TRACKING; HUMAN-HEART; STRAIN-RATE; DEFORMATION AB Imaging the left ventricular mechanical and hemodynamic response to the stress of exercise may offer early prognosis in select patients with cardiac disease. Here, we demonstrate the feasibility of obtaining simultaneous measurements of longitudinal strain and transvalvular blood velocity during supine bicycle exercise stress in a wide bore magnetic resonance scanner. Combining information from the two datasets, we observe that although the time to peak strain (33.28 +/- 1.86 versus 25.7 +/- 2.12 as % of R-R interval) and time to peak mitral inflow velocity (44.37 +/- 5.21 versus 35.5 +/- 4.19 as % of R-R interval) from R-wave of the QRS complex occurred earlier during stress, the time from peak strain to peak mitral inflow velocity was not statistically different (16.5 +/- 3.23 versus 13.4 +/- 3.06). Further, the percentage of longitudinal relaxation at peak mitral inflow velocity was higher during stress (63.5 +/- 7.72 versus 84.32 +/- 6.24). These results suggest that although diastole is shortened, early diastolic filling efficiency is augmented during exercise stress in normal volunteers in an effort to maintain stroke volume. Magn Reson Med 65:51-59, 2011. (c) 2010 Wiley-Liss, Inc. C1 [Sampath, Smita; Derbyshire, John Andrew; McVeigh, Elliot R.] NHLBI, Cardiac Energet Lab, Div Intramural Res, NIH,DHHS, Bethesda, MD 20892 USA. [Ledesma-Carbayo, Maria J.] Univ Politecn Madrid, ETSI Telecomunicac, Madrid, Spain. RP Sampath, S (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, Anlyan Ctr, 300 Cedar St,N131, New Haven, CT 06520 USA. EM smita.sampath@yale.edu RI Ledesma-Carbayo, Maria /D-5529-2009 OI Ledesma-Carbayo, Maria /0000-0001-6846-3923 FU National Heart Lung and Blood Institute [Z01HL004609]; Spanish Ministry of Education; Ministry of Industry [TIN2007-68048-C02-01] FX Grant sponsor: Intramural Research Program of the National Heart Lung and Blood Institute; Grant number: Z01HL004609; Grant sponsor: Spanish Ministry of Education and the CDTEAM Project from the Ministry of Industry; Grant number: TIN2007-68048-C02-01. NR 26 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2011 VL 65 IS 1 BP 51 EP 59 DI 10.1002/mrm.22668 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 703FM UT WOS:000285963500007 PM 21053325 ER PT S AU Ouwerkerk, R AF Ouwerkerk, Ronald BE Modo, M Bulte, JWM TI Sodium MRI SO MAGNETIC RESONANCE NEUROIMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE MRI; sodium; Na-23; other nuclei; cancer; stroke; brain ID FOCAL CEREBRAL-ISCHEMIA; QUANTUM-FILTERED NA-23; PERFUSED RAT-HEART; MAGNETIC-RESONANCE; HUMAN BRAIN; TISSUE SODIUM; IN-VIVO; MYOCARDIAL-INFARCTION; PROJECTION TECHNIQUE; INVERSION-RECOVERY AB Sodium (Na-23) imaging has a place somewhere between H-1-MRI and MR spectroscopy (MRS). Like MRS it potentially provides information on metabolic processes, but only one single resonance of ionic Na-23 is observed. Therefore pulse sequences do not need to code for a chemical shift dimension, allowing Na-23 images to be obtained at high resolutions as compared to MRS. In this chapter the biological significance of sodium in the brain will be discussed, as well as methods for observing it with Na-23-MRI. Many vital cellular processes and interactions in excitable tissues depend on the maintenance of a low intracellular and high extracellular sodium concentration. Healthy cells maintain this concentration gradient at the cost of energy. Leaky cell membranes or an impaired energy metabolism immediately leads to an increase in cytosolic total tissue sodium. This makes sodium a biomarker for ischemia, cancer, excessive tissue activation, or tissue damage as might be caused by ablation therapy. Special techniques allow quantification of tissue sodium for the monitoring of disease or therapy in longitudinal studies or preferential observation of the intracellular component of the tissue sodium. New methods and high-field magnet technology provide new opportunities for Na-23-MRI in clinical and biomedical research. C1 NIDDK, NIH, Bethesda, MD USA. RP Ouwerkerk, R (reprint author), NIDDK, NIH, Bethesda, MD USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 74 TC 21 Z9 21 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-991-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 711 BP 175 EP 201 DI 10.1007/978-1-61737-992-5_8 D2 10.1007/978-1-61737-992-5 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Chemistry; Radiology, Nuclear Medicine & Medical Imaging GA BTS51 UT WOS:000287980300008 PM 21279602 ER PT S AU Duyn, JH AF Duyn, Jozef H. BE Modo, M Bulte, JWM TI High-Field MRI of Brain Iron SO MAGNETIC RESONANCE NEUROIMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Iron; ferritin; MRI; brain; magnetic susceptibility ID WHITE-MATTER CONTRAST; MAGNETIC-FIELD; TRACKING SYSTEM; SUSCEPTIBILITY; PHASE; SENSITIVITY; IMAGES; MOTION; ORIENTATION; MECHANISMS AB Recent developments in high-field MRI have provided opportunities to detect iron in human brain with much improved sensitivity. The combination of increased magnetic field strength with multi-channel detectors has made it possible to routinely obtain images at about 300 mu m resolution. These images can be sensitized to tissue iron by exploiting the improved magnetic susceptibility contrast at high field. Together, these techniques have the potential to map the fine scale distribution of iron in human brain at the level of fiber bundles and cortical laminae, and may aid in the understanding of the role and transport of iron in normal brain and in disease. In this chapter, we will look at these techniques in detail and present some examples of high-field MRI data of human brain. C1 NINDS, Adv MRI Sect, NIH, Bethesda, MD 20892 USA. RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 FU Intramural NIH HHS [Z01 NS002990-09] NR 33 TC 10 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-991-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 711 BP 239 EP 249 DI 10.1007/978-1-61737-992-5_11 D2 10.1007/978-1-61737-992-5 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Chemistry; Radiology, Nuclear Medicine & Medical Imaging GA BTS51 UT WOS:000287980300011 PM 21279605 ER PT S AU Silva, AC Liu, JJV Hirano, Y Leoni, RF Merkle, H Mackel, JB Zhang, XF Nascimento, GC Stefanovic, B AF Silva, Afonso C. Liu, Junjie V. Hirano, Yoshiyuki Leoni, Renata F. Merkle, Hellmut Mackel, Julie B. Zhang, Xian Feng Nascimento, George C. Stefanovic, Bojana BE Modo, M Bulte, JWM TI Longitudinal Functional Magnetic Resonance Imaging in Animal Models SO MAGNETIC RESONANCE NEUROIMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Anesthesia; awake; brain; BOLD; cerebral blood flow; cerebral blood volume; neurovascular coupling; non-human primates; rodents; songbirds ID CEREBRAL-BLOOD-FLOW; CHLORALOSE ANESTHETIZED RATS; AWAKE RHESUS-MONKEYS; ALPHA-CHLORALOSE; SOMATOSENSORY CORTEX; FOREPAW STIMULATION; BRAIN ACTIVATION; CONSCIOUS RATS; ISOFLURANE ANESTHESIA; OXYGEN-CONSUMPTION AB Functional magnetic resonance imaging (fMRI) has had an essential role in furthering our understanding of brain physiology and function. fMRI techniques are nowadays widely applied in neuroscience research, as well as in translational and clinical studies. The use of animal models in fMRI studies has been fundamental in helping elucidate the mechanisms of cerebral blood-flow regulation, and in the exploration of basic neuroscience questions, such as the mechanisms of perception, behavior, and cognition. Because animals are inherently non-compliant, most fMRI performed to date have required the use of anesthesia, which interferes with brain function and compromises interpretability and applicability of results to our understanding of human brain function. An alternative approach that eliminates the need for anesthesia involves training the animal to tolerate physical restraint during the data acquisition. In the present chapter, we review these two different approaches to obtaining fMRI data from animal models, with a specific focus on the acquisition of longitudinal data from the same subjects. C1 [Silva, Afonso C.; Liu, Junjie V.; Hirano, Yoshiyuki; Leoni, Renata F.; Merkle, Hellmut; Mackel, Julie B.; Zhang, Xian Feng] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. [Nascimento, George C.] Univ Fed Rio Grande do Norte, Dept Biomed Engn, BR-59072970 Natal, RN, Brazil. [Stefanovic, Bojana] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. RP Silva, AC (reprint author), Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. RI Bulte, Jeff/A-3240-2008; OI Bulte, Jeff/0000-0003-1202-1610; Leoni, Renata/0000-0002-4568-0746 FU Intramural NIH HHS [ZIA NS003012-05, ZIA NS003041-05] NR 86 TC 22 Z9 22 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-991-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 711 BP 281 EP 302 DI 10.1007/978-1-61737-992-5_14 D2 10.1007/978-1-61737-992-5 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Chemistry; Radiology, Nuclear Medicine & Medical Imaging GA BTS51 UT WOS:000287980300014 PM 21279608 ER PT S AU Matsumoto, K Hyodo, F Anzai, K Utsumi, H Mitchell, JB Krishna, MC AF Matsumoto, Ken-ichiro Hyodo, Fuminori Anzai, Kazunori Utsumi, Hideo Mitchell, James B. Krishna, Murali C. BE Modo, M Bulte, JWM TI Brain Redox Imaging SO MAGNETIC RESONANCE NEUROIMAGING: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Redox imaging; nitroxyl contrast agents; Overhauser MRI; electron paramagnetic resonance imaging; reactive oxygen species; hypoxia; hyperoxia ID ELECTRON-SPIN-RESONANCE; FREE-RADICAL REACTIONS; SENSITIVE CONTRAST AGENTS; IN-VIVO MEASUREMENT; L-BAND ESR; PHARMACOKINETIC ANALYSIS; NONINVASIVE ANALYSIS; NITROXYL RADICALS; STABLE NITROXIDE; MURINE TUMOR AB Nitroxyl contrast agents (nitroxyl radicals, also known as nitroxide) are paramagnetic species, which can react with reactive oxygen species (ROS) to lose paramagnetism to be diamagnetic species. The paramagnetic nitroxyl radical forms can be detected by using electron paramagnetic resonance imaging (EPRI), Overhauser MRI (OMRI), or MRI. The time course of in vivo image intensity induced by paramagnetic redox-sensitive contrast agent can give tissue redox information, which is the so-called redox imaging technique. The redox imaging technique employing a blood-brain barrier permeable nitroxyl contrast agent can be applied to analyze the pathophysiological functions in the brain. A brief theory of redox imaging techniques is described, and applications of redox imaging techniques to brain are introduced. C1 [Matsumoto, Ken-ichiro; Anzai, Kazunori] Natl Inst Radiol Sci, Radiat Modifier Res Team, Heavy Ion Radiobiol Res Grp, Res Ctr Charged Particle Therapy, Chiba 260, Japan. [Hyodo, Fuminori; Utsumi, Hideo] Kyushu Univ, Innovat Ctr Med Redox Nav, Fukuoka 812, Japan. [Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. RP Matsumoto, K (reprint author), Natl Inst Radiol Sci, Radiat Modifier Res Team, Heavy Ion Radiobiol Res Grp, Res Ctr Charged Particle Therapy, Chiba 260, Japan. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 69 TC 9 Z9 9 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61737-991-8 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 711 BP 397 EP 419 DI 10.1007/978-1-61737-992-5_20 D2 10.1007/978-1-61737-992-5 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Chemistry; Radiology, Nuclear Medicine & Medical Imaging GA BTS51 UT WOS:000287980300020 PM 21279614 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Polysaccharides: Their Characteristics and Marine Sources SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID SEA HYDROTHERMAL VENTS; BACTERIAL EXOPOLYSACCHARIDES; COMMERCIAL PRODUCTION; SOUTHERN-OCEAN; FOOD; BIOTECHNOLOGY; MICROALGAE; SEAWEED; PERSPECTIVES; ORGANISMS C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 75 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 3 EP 26 D2 10.1201/b10516 PG 24 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700002 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Marine Polysaccharides Food Applications Preface SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Editorial Material; Book Chapter C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP XV EP XVI D2 10.1201/b10516 PG 2 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700001 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Functional Properties Relevant to Food Product Development SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID PROTEIN-POLYSACCHARIDE INTERACTIONS; RHEOLOGICAL PROPERTIES; FLAVOR RELEASE; FLUID GELS; HYDROCOLLOIDS; STABILITY; TEXTURE; EMULSIONS; FOAMS; MICROSTRUCTURE C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 96 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 27 EP 60 D2 10.1201/b10516 PG 34 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700003 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Crustacean Polysaccharides: Chitin and Chitosan SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID FUNCTIONAL-PROPERTIES; SHRIMP SHELLS; PHYSICOCHEMICAL CHARACTERISTICS; MARINE BIOTECHNOLOGY; CHEMICAL-COMPOSITION; N-ACETYLATION; IN-SITU; EXTRACTION; PRODUCTS; WATER C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 88 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 61 EP 88 D2 10.1201/b10516 PG 28 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700004 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Polysaccharides from Seaweed and Microalgae SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID KAPPA-CARRAGEENAN GELS; LOCUST BEAN GUM; RHEOLOGICAL BEHAVIOR; BROWN SEAWEEDS; NUTRITIONAL ASPECTS; EDIBLE SEAWEEDS; DIETARY FIBER; EXTRACELLULAR POLYSACCHARIDES; COLORIMETRIC DETERMINATION; MARINE POLYSACCHARIDES C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 127 TC 1 Z9 1 U1 1 U2 3 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 89 EP 134 D2 10.1201/b10516 PG 46 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700005 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Extracellular Polysaccharides from Marine Microorganisms SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID SEA HYDROTHERMAL VENTS; LACTIC-ACID BACTERIA; EXOPOLYSACCHARIDE PRODUCTION; SPHINGOMONAS-PAUCIMOBILIS; MICROBIAL POLYSACCHARIDES; CHEMICAL-CHARACTERIZATION; PSEUDOMONAS-FLUORESCENS; LEUCONOSTOC-DEXTRANICUM; HALOMONAS-EURIHALINA; GELLING PROPERTIES C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 98 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 135 EP 160 D2 10.1201/b10516 PG 26 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700006 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Crustacean Polysaccharides: Food Applications SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID IN-WATER EMULSIONS; SHELF-LIFE; ANTIMICROBIAL ACTIVITY; PHYSICOCHEMICAL PROPERTIES; ANTIOXIDATIVE ACTIVITIES; ANTIBACTERIAL ACTIVITY; CHITOSAN TREATMENT; GELLING PROPERTIES; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 111 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 163 EP 189 D2 10.1201/b10516 PG 27 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700007 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Seaweed, Microalgae, and Their Polysaccharides: Food Applications SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID LOCUST-BEAN GUM; KAPPA-CARRAGEENAN; DIETARY FIBER; PHYSICOCHEMICAL PROPERTIES; QUALITY CHARACTERISTICS; VISCOELASTIC PROPERTIES; DIFFERENT HYDROCOLLOIDS; LAMBDA-CARRAGEENAN; IOTA-CARRAGEENAN; EDIBLE SEAWEEDS C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 150 TC 1 Z9 1 U1 1 U2 3 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 191 EP 235 D2 10.1201/b10516 PG 45 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700008 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Extracellular Polysaccharides from Non-Marine and Marine Microorganisms: Food Applications SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID SEA HYDROTHERMAL VENTS; BACTERIAL EXOPOLYSACCHARIDES; RHEOLOGICAL PROPERTIES; HALOMONAS-EURIHALINA; GELLAN GUM; CHEMICAL-COMPOSITION; HYDROCOLLOIDS; STRAIN; EMULSIFIER; CURDLAN C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 94 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 237 EP 257 D2 10.1201/b10516 PG 21 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700009 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Edible Films and Carrier Matrices from Marine Polysaccharides SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID SHELF-LIFE EXTENSION; ENHANCING MICROBIAL SAFETY; CHITOSAN COMPOSITE FILMS; WATER-VAPOR BARRIER; FRESH-CUT FRUITS; PACKAGING TECHNOLOGIES; MECHANICAL-PROPERTIES; ANTIMICROBIAL ACTIVITY; POSTHARVEST QUALITY; BIODEGRADABLE FILMS C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 161 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 259 EP 307 D2 10.1201/b10516 PG 49 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700010 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Safety and Regulatory Aspects SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID CARRAGEENAN; SEAWEED; DEGRADATION; PRODUCTS; CHITOSAN C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 45 TC 0 Z9 0 U1 1 U2 3 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 309 EP 327 D2 10.1201/b10516 PG 19 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700011 ER PT B AU Venugopal, V AF Venugopal, Vazhiyil BA Venugopal, V BF Venugopal, V TI Biomedical Applications of Marine Polysaccharides: An Overview SO MARINE POLYSACCHARIDES: FOOD APPLICATIONS LA English DT Article; Book Chapter ID IN-VITRO CHARACTERIZATION; DRUG-DELIVERY; SULFATED POLYSACCHARIDES; ANTICOAGULANT ACTIVITY; ALGINATE HYDROGELS; GREEN-ALGAE; CHITOSAN; NANOPARTICLES; RELEASE; CHITIN C1 [Venugopal, Vazhiyil] Cent Inst Fisheries Technol, Cochin, Kerala, India. [Venugopal, Vazhiyil] Bhabha Atom Res Ctr, Seafood Technol Sect, Food Technol Div, Bombay 400085, Maharashtra, India. [Venugopal, Vazhiyil] NIH, Bethesda, MD 20892 USA. [Venugopal, Vazhiyil] Natl Acad Agr Sci, New Delhi, India. RP Venugopal, V (reprint author), Mem Univ Newfoundland, St John, NF, Canada. EM venugopalmenon@hotmail.com NR 94 TC 0 Z9 0 U1 1 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1527-4; 978-1-4398-1526-7 PY 2011 BP 331 EP 351 D2 10.1201/b10516 PG 21 WC Food Science & Technology SC Food Science & Technology GA BC6MQ UT WOS:000354121700012 ER PT J AU Gilfillan, AM Austin, SJ Metcalfe, DD AF Gilfillan, Alasdair M. Austin, Sarah J. Metcalfe, Dean D. BE Gilfillan, AM Metcalfe, DD TI MAST CELL BIOLOGY: Introduction and Overview SO MAST CELL BIOLOGY: CONTEMPORARY AND EMERGING TOPICS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID FC-EPSILON-RI; TOLL-LIKE RECEPTORS; PHOSPHOINOSITIDE 3-KINASE; EICOSANOID MEDIATORS; SIGNALING PATHWAYS; ALLERGIC RESPONSE; CHANNEL FUNCTION; CUTTING EDGE; LIPID RAFTS; ACTIVATION AB In recent years, the field of mast cell biology has expanded well beyond the boundaries of atopic disorders and anaphylaxis, on which it has been historically focused. The biochemical and signaling events responsible for the development and regulation of mast cells has been increasingly studied, aided in large part by novel breakthroughs in laboratory techniques used to study these cells. The result of these studies has been a more comprehensive definition of mast cells that includes added insights to their overall biology as well as the various disease states that can now be traced to defects in mast cells. This introductory chapter outlines and highlights the various topics of mast cell biology that will be discussed in further detail in subsequent chapters. C1 [Gilfillan, Alasdair M.; Austin, Sarah J.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov; agilfillan@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000967-05] NR 77 TC 37 Z9 38 U1 1 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 716 BP 2 EP 12 PG 11 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BUQ43 UT WOS:000290066600001 PM 21713648 ER PT J AU Ma, HT Beaven, MA AF Ma, Hong-Tao Beaven, Michael A. BE Gilfillan, AM Metcalfe, DD TI REGULATORS OF Ca2+ SIGNALING IN MAST CELLS: Potential Targets for Treatment of Mast Cell-Related Diseases? SO MAST CELL BIOLOGY: CONTEMPORARY AND EMERGING TOPICS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID FC-EPSILON-RI; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; ACTIVATED CALCIUM CURRENT; ANAPHYLACTIC HISTAMINE-SECRETION; CYTOSOLIC PHOSPHOLIPASE A(2); SARCO-ENDOPLASMIC-RETICULUM; STORE-OPERATED CHANNELS; XENOPUS-LAEVIS OOCYTES; THAPSIA-GARGANICA L AB A calcium signal is essential for degranulation, generation of eicosanoids and optimal production of cytokines in mast cells in response to antigen and other stimulants. The signal is initiated by phospholipase C-mediated production of inositol 1,4,5-trisphosphate resulting in release of stored Ca2+ from the endoplasmic reticulum (ER) and Golgi. Depletion of these stores activates influx of extracellular Ca2+, usually referred to as store-operated calcium entry (SOCE), through the interaction of the Ca2+-sensor, stromal interacting molecule-1 (STIM1), in ER with Orai1(CRACM1) and transient receptor potential canonical (TRPC) channel proteins in the plasma membrane (PM). This interaction is enabled by microtubular-directed reorganization of ER to form ER/PM contact points or "punctae" in which STIM1 and channel proteins colocalize. The ensuing influx of Ca2+ replenishes Ca2+ stores and sustains elevated levels of cytosolic Ca2+ ions-the obligatory signal for mast-cell activation. In addition, the signal can acquire spatial and dynamic characteristics (e.g., calcium puffs, waves, oscillations) that encode signals for specific functional outputs. This is achieved by coordinated regulation of Ca2+ fluxes through ATP-dependent Ca2+-pumps and ion exchangers in mitochondria, ER and PM. As discussed in this chapter, studies in mast cells revealed much about the mechanisms described above but little about allergic and autoimmune diseases although studies in other types of cells have exposed genetic defects that lead to aberrant calcium signaling in immune diseases. Pharmacologic agents that inhibit or activate the regulatory components of calcium signaling in mast cells are also discussed along with the prospects for development of novel SOCE inhibitors that may prove beneficial in the treatment inflammatory mast-cell related diseases. C1 [Ma, Hong-Tao; Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM beavenm@nhlbi.nih.gov FU Intramural NIH HHS NR 260 TC 41 Z9 41 U1 1 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 716 BP 62 EP 90 PG 29 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BUQ43 UT WOS:000290066600005 PM 21713652 ER PT J AU Olivera, A Rivera, J AF Olivera, Ana Rivera, Juan BE Gilfillan, AM Metcalfe, DD TI AN EMERGING ROLE FOR THE LIPID MEDIATOR SPHINGOSINE-1-PHOSPHATE IN MAST CELL EFFECTOR FUNCTION AND ALLERGIC DISEASE SO MAST CELL BIOLOGY: CONTEMPORARY AND EMERGING TOPICS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID FC-EPSILON-RI; SPHINGOSINE 1-PHOSPHATE METABOLISM; OPERATED CALCIUM-CHANNELS; LYMPHOCYTE EGRESS; ATOPIC-DERMATITIS; IN-VIVO; SPHINGOLIPID METABOLISM; INFLAMMATORY RESPONSES; TOPICAL APPLICATION; DENDRITIC CELLS AB Sphingosine-1-phosphate (S1P) plays important roles regulating functions of diverse biological systems, including the immune system. S1P affects immune cell function mostly by acting through its receptors at the cell membrane but it can also induce S1P receptor-independent responses in the cells where it is generated. S1P produced in allergically-stimulated mast cells mediates degranulation, cytokine and lipid mediator production and migration of mast cells towards antigen by mechanisms that are both S1P receptor-dependent and independent. Even in the absence of an antigen challenge, the differentiation and responsiveness of mast cells can be affected by chronic exposure to elevated S1P from a nonmast cell source, which may occur under pathophysiological conditions, potentially leading to the hyper-responsiveness of mast cells. The role of S1P extends beyond the regulation of the function of mast cells to the regulation of the surrounding or distal environment. S1P is exported out of antigen-stimulated mast cells and into the extracellular space and the resulting S1P gradient within the tissue may influence diverse surrounding tissue cells and several aspects of the allergic disease, such as inflammation or tissue remodeling. Furthermore, recent findings indicate that vasoactive mediators released systemically by mast cells induce the production of S1P in nonhematopoietic compartments, where it plays a role in regulating the vascular tone and reducing the hypotension characteristic of the anaphylactic shock and thus helping the recovery. The dual actions of S1P, promoting the immediate response of mast cells, while controlling the systemic consequences of mast cell activity will be discussed in detail. C1 [Olivera, Ana; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Olivera, A (reprint author), NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. EM oliveraa@mail.nih.gov; juan.rivera@nih.gov FU Intramural NIH HHS [ZIA AR041155-05] NR 107 TC 31 Z9 33 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2011 VL 716 BP 123 EP 142 PG 20 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BUQ43 UT WOS:000290066600008 PM 21713655 ER PT J AU El-Mohandes, AAE Kiely, M Gantz, MG El-Khorazaty, MN AF El-Mohandes, Ayman A. E. Kiely, Michele Gantz, Marie G. El-Khorazaty, M. Nabil TI Very Preterm Birth is Reduced in Women Receiving an Integrated Behavioral Intervention: A Randomized Controlled Trial SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE African-American; Birth weight; Pregnancy; Gestational age ID AFRICAN-AMERICAN WOMEN; ACTIVE PERINATAL MANAGEMENT; TERTIARY CARE CENTERS; RISK-FACTORS; ETHNIC-DIFFERENCES; SMOKING-CESSATION; PREGNANT-WOMEN; WEIGHT INFANTS; OUTCOMES; DEPRESSION AB This study examines whether an integrated behavioral intervention with proven efficacy in reducing psycho-behavioral risks (smoking, environmental tobacco smoke exposure (ETSE), depression, and intimate partner violence (IPV)) in African-Americans is associated with improved pregnancy outcomes. A randomized controlled trial targeting risks during pregnancy was conducted in the District of Columbia. African-American women were recruited if reporting at least one of the risks mentioned above. Randomization to intervention or usual care was site and risk specific. Sociodemographic, health risk and pregnancy outcome data were collected. Data on 819 women, and their singleton live born infants were analyzed using an intent-to-treat approach. Bivariate analyses preceded a reduced logistical model approach to elucidate the effect of the intervention on the reduction of prematurity and low birth weight. The incidence of low birthweight (LBW) was 12% and very low birthweight (VLBW) was 1.6%. Multivariate logistic regression results showed that depression was associated with LBW (OR = 1.71, 95% CI = 1.12-2.62). IPV was associated with preterm birth (PTB) and very preterm birth (VPTB) (OR 1.64, 95% CI = 1.07-2.51, OR = 2.94, 95% CI = 1.40-6.16, respectively). The occurrence of VPTB was significantly reduced in the intervention compared to the usual care group (OR = 0.42, 95% CI = 0.19-0.93). Our study confirms the significant associations between multiple psycho-behavioral risks and poor pregnancy outcomes, including LBW and PTB. Our behavioral intervention with demonstrated efficacy in addressing multiple risk factors simultaneously reduced VPTB within an urban minority population. C1 [Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [El-Mohandes, Ayman A. E.] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE 68198 USA. [Gantz, Marie G.; El-Khorazaty, M. Nabil] RTI Int, Stat & Epidemiol Unit, Rockville, MD 20852 USA. RP Kiely, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Bldg,Rm 7B-05,MSC 7510, Bethesda, MD 20892 USA. EM aelmohandes@unmc.edu; kielym@nih.gov; mgantz@rti.org; nek@rti.org FU Intramural NIH HHS [Z99 HD999999]; NICHD NIH HHS [U18 HD031919-07, 3U18HD030445, 3U18HD030447, 3U18HD031919, 5U18HD036104, 5U18HD31206, U18 HD030445, U18 HD030445-07, U18 HD030447, U18 HD030447-07, U18 HD031206, U18 HD031206-07, U18 HD031919, U18 HD036104, U18 HD036104-02] NR 39 TC 29 Z9 30 U1 1 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 EI 1573-6628 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD JAN PY 2011 VL 15 IS 1 BP 19 EP 28 DI 10.1007/s10995-009-0557-z PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 703TM UT WOS:000286004200004 PM 20082130 ER PT J AU Acuna-Soto, R Castaneda-Davila, L Chowell, G AF Acuna-Soto, Rodolfo Castaneda-Davila, Luis Chowell, Gerardo TI A PERSPECTIVE ON THE 2009 A/H1N1 INFLUENZA PANDEMIC IN MEXICO SO MATHEMATICAL BIOSCIENCES AND ENGINEERING LA English DT Article DE Pandemic influenza; reproduction number; epidemic model; H1N1 influenza; metapopulation model ID A H1N1 VIRUS; SEASONAL INFLUENZA; UNITED-STATES; MORTALITY; TRANSMISSIBILITY; AUSTRALIA; SPREAD; WAVE; INFECTION; PATTERNS AB In this article, we provide a chronological description of the 2009 H1N1 influenza pandemic in Mexico from the detection of severe respiratory disease among young adults in central Mexico and the identification of the novel swine-origin influenza virus to the response of Mexican public health authorities with the swift implementation of the National Preparedness and Response Plan for Pandemic Influenza. Furthermore, we review some features of the 2009 H1N1 influenza pandemic in Mexico in relation to the devastating 1918-1920 influenza pandemic and discuss opportunities for the application of mathematical modeling in the transmission dynamics of pandemic influenza. The value of historical data in increasing our understanding of past pandemic events is highlighted. C1 [Acuna-Soto, Rodolfo; Castaneda-Davila, Luis] Univ Nacl Autonoma Mexico, Fac Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico. [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ 85287 USA. [Chowell, Gerardo] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Acuna-Soto, R (reprint author), Univ Nacl Autonoma Mexico, Fac Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico. EM acunasoto.rodolfo@gmail.com; cdsiul@hotmail.com; gchowell@asu.edu RI Chowell, Gerardo/F-5038-2012 OI Chowell, Gerardo/0000-0003-2194-2251 NR 57 TC 2 Z9 2 U1 0 U2 4 PU AMER INST MATHEMATICAL SCIENCES PI SPRINGFIELD PA PO BOX 2604, SPRINGFIELD, MO 65801-2604 USA SN 1547-1063 J9 MATH BIOSCI ENG JI Math. Biosci. Eng. PD JAN PY 2011 VL 8 IS 1 BP 223 EP 238 DI 10.3934/mbe.2011.8.223 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 715JD UT WOS:000286879500014 PM 21361409 ER PT S AU Jiang, B AF Jiang, Bo BE Schmalz, MS Ritter, GX Barrera, J Astola, JT TI Edge Pattern Analysis for Edge Detection and Localization SO MATHEMATICS OF DATA/IMAGE PATTERN CODING, COMPRESSION, AND ENCRYPTION WITH APPLICATIONS XIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Mathematics of Data/Image Pattern Coding, Compression, and Encryption with Applications XIII CY AUG 21-24, 2011 CL San Diego, CA SP SPIE DE Edge Pattern; Edge Pattern Analysis; Ramp edge; Step edge; Impulse Edge; Edge Detection; Localization AB Edge detection process plays an important role in image processing, and at its most basic level classifies image pixels into edges and non-edge pixels. The accuracy of edge detection methods in general image processing determines the eventual success or failure of computerized analysis procedures which follow the initial edge detection determinations. In view of this downstream impact on pattern processing, considerable care should be taken to improve the accuracy of the front-end edge detection. In general, edges would be considered as abrupt changes or discontinuity in intensity of an image. Therefore, most of edge detection algorithms are designed to capture signal discontinuities but the spatial character of especially complex edge patterns has not received enough attention. Edges can be divided into basic patterns such as ramp, impulse, and step: different types have different shapes and consequent mathematical properties. In this paper, the behavior of various edge patterns, under different order derivatives in the discrete domain, are examined and analyzed to determine how to accurately detect and localize these edge patterns, especially reducing double edge response that is one important drawback to the derivative method. General rules about the depiction of edge patterns are proposed. Asides from the ideal patterns already described, other pattern types, such as stair and roof, are examined to broaden the initial analysis. Experiments conducted to test my propositions support the idea that edge patterns are instructive in enhancing the accuracy of edge detection and localization. C1 NIA, Hampton, VA 23666 USA. RP Jiang, B (reprint author), NIA, Hampton, VA 23666 USA. EM bo.jiang@nianet.org NR 18 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-746-9 J9 PROC SPIE PY 2011 VL 8136 AR 81360H DI 10.1117/12.892423 PG 13 WC Engineering, Electrical & Electronic; Mathematics, Applied; Optics SC Engineering; Mathematics; Optics GA BXY00 UT WOS:000297584000016 ER PT J AU D'Souza, CA Kronstad, JW Taylor, G Warren, R Yuen, M Hu, G Jung, WH Sham, A Kidd, SE Tangen, K Lee, N Zeilmaker, T Sawkins, J McVicker, G Shah, S Gnerre, S Griggs, A Zeng, Q Bartlett, K Li, W Wang, X Heitman, J Stajich, JE Fraser, JA Meyer, W Carter, D Schein, J Krzywinski, M Kwon-Chung, KJ Varma, A Wang, J Brunham, R Fyfe, M Ouellette, BFF Siddiqui, A Marra, M Jones, S Holt, R Birren, BW Galagan, JE Cuomo, CA AF D'Souza, C. A. Kronstad, J. W. Taylor, G. Warren, R. Yuen, M. Hu, G. Jung, W. H. Sham, A. Kidd, S. E. Tangen, K. Lee, N. Zeilmaker, T. Sawkins, J. McVicker, G. Shah, S. Gnerre, S. Griggs, A. Zeng, Q. Bartlett, K. Li, W. Wang, X. Heitman, J. Stajich, J. E. Fraser, J. A. Meyer, W. Carter, D. Schein, J. Krzywinski, M. Kwon-Chung, K. J. Varma, A. Wang, J. Brunham, R. Fyfe, M. Ouellette, B. F. F. Siddiqui, A. Marra, M. Jones, S. Holt, R. Birren, B. W. Galagan, J. E. Cuomo, C. A. TI Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts SO MBIO LA English DT Article ID VANCOUVER-ISLAND OUTBREAK; GENE FAMILY EVOLUTION; NEOFORMANS VAR GATTII; BRITISH-COLUMBIA; PACIFIC-NORTHWEST; SEQUENCE ALIGNMENT; UNITED-STATES; FUNGI; MENINGITIS; CANADA AB Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance. IMPORTANCE Isolates of Cryptococcus gattii are currently causing an outbreak of cryptococcosis in western North America, and most of the cases occurred in the absence of coinfection with HIV. This pattern is therefore in stark contrast to the current global burden of one million annual cases of cryptococcosis, caused by the related species Cryptococcus neoformans, in the HIV/AIDS population. The genome sequences of two outbreak-associated major genotypes of C. gattii reported here provide insights into genome variation within and between cryptococcal species. These sequences also provide a resource to further evaluate the epidemiology of cryptococcal disease and to evaluate the role of pathogen genes in the differential interactions of C. gattii and C. neoformans with immunocompromised and immunocompetent hosts. C1 [D'Souza, C. A.; Kronstad, J. W.; Yuen, M.; Hu, G.; Sham, A.; Kidd, S. E.; Tangen, K.; Lee, N.; Zeilmaker, T.; Sawkins, J.; McVicker, G.; Shah, S.; Wang, J.; Ouellette, B. F. F.] Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada. [Taylor, G.; Warren, R.; Schein, J.; Krzywinski, M.; Siddiqui, A.; Marra, M.; Jones, S.; Holt, R.] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Jung, W. H.] Chung Ang Univ, Dept Biotechnol, Anseong, Gyeonggi Do, South Korea. [Kidd, S. E.; Meyer, W.] Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol,Sydney Emerging Dis &, Sydney Med Sch,Mol Mycol Res Lab,Westmead Milleni, Westmead, NSW 2145, Australia. [Gnerre, S.; Griggs, A.; Zeng, Q.; Birren, B. W.; Galagan, J. E.; Cuomo, C. A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Bartlett, K.] Univ British Columbia, Sch Occupat & Environm Hyg, Vancouver, BC V5Z 1M9, Canada. [Li, W.; Wang, X.; Heitman, J.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. [Stajich, J. E.] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA. [Fraser, J. A.; Brunham, R.] Univ Queensland, Ctr Infect Dis Res, Sch Chem & Mol Biosci, Brisbane, Qld, Australia. [Carter, D.] Univ Sydney, Sch Mol Biosci, Sydney, NSW 2006, Australia. [Kwon-Chung, K. J.; Varma, A.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. British Columbia Ctr Dis Control, Vancouver, BC, Canada. [Fyfe, M.] Vancouver Isl Hlth Author, Off Med Hlth Officer, Victoria, BC, Canada. [Ouellette, B. F. F.] Ontario Inst Canc Res, Toronto, ON, Canada. RP Kronstad, JW (reprint author), Univ British Columbia, Michael Smith Labs, Vancouver, BC V5Z 1M9, Canada. EM kronstad@interchange.ubc.ca RI Wang, Xuying/C-8053-2011; Fraser, James/B-4918-2012; Kidd, Sarah/A-1731-2009; Stajich, Jason/C-7297-2008; Kidd, Sarah/N-1362-2013; Tang, Macy/B-9798-2014; Holt, Robert/C-3303-2009; Meyer, Wieland/G-1204-2015; Jones, Steven/C-3621-2009; Marra, Marco/B-5987-2008; OI Cuomo, Christina/0000-0002-5778-960X; Fraser, James/0000-0001-5724-5285; Kidd, Sarah/0000-0002-5957-4178; Stajich, Jason/0000-0002-7591-0020; Kidd, Sarah/0000-0002-5957-4178; Meyer, Wieland/0000-0001-9933-8340; Galagan, James/0000-0003-0542-3291 FU Genome Canada; Genome British Columbia; National Institute of Allergy and Infectious Disease [R01 AI053721]; Canadian Institutes of Health Research; National Human Genome Research Institute [U54HG003067]; National Institute of Allergy and Infectious Diseases [AI50113]; National Institutes of Health (NIH/NIAID, MD); National Health and Medical Research Council Australia [990738] FX The sequencing and annotation of the WM276 genome was funded by Genome Canada and Genome British Columbia and by grants from the National Institute of Allergy and Infectious Disease (R01 AI053721) and the Canadian Institutes of Health Research to J.W.K. Sequencing and annotation of the R265 genome at the Broad Institute was supported by the National Human Genome Research Institute (grant U54HG003067). Additional support was obtained from an R01 grant (AI50113) to J.H. and an intramural program grant to K.J.K.-C. and A. V. from the National Institute of Allergy and Infectious Diseases and the National Institutes of Health (NIH/NIAID, MD), the National Health and Medical Research Council Australia Research grant 990738 to W. M. for the construction of physical maps of the C. gattii genomes, and a grant to D. C. by the Howard Hughes Medical Institute under the International Scholars Program (55000640). NR 97 TC 65 Z9 71 U1 0 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2011 VL 2 IS 1 AR e00342-10 DI 10.1128/mBio.00342-10 PG 11 WC Microbiology SC Microbiology GA 734XK UT WOS:000288375400022 PM 21304167 ER PT J AU Bletzer, KV Yuan, NP Koss, MP Polacca, M Eaves, ER Goldman, D AF Bletzer, Keith V. Yuan, Nicole P. Koss, Mary P. Polacca, Mona Eaves, Emery R. Goldman, David TI Taking Humor Seriously: Talking about Drinking in Native American Focus Groups SO MEDICAL ANTHROPOLOGY LA English DT Article DE adults and adolescents; drinking; humor; linguistic analysis; Native Americans ID SUBSTANCE-USE; ALCOHOL-USE; INDIAN ADOLESCENTS; CULTURE; RISK; COMMUNITIES; POPULATIONS; PERSPECTIVE; DISPARITIES; ADDICTION AB Focus groups provide a source of data that highlight community ideas on a topic of interest. How interview data will be utilized varies by project. With this in mind, we identify ways that focus group data from a particular population (Native American) articulate a health issue of individual tribal concern (alcohol consumption). Taking our analytic framework from linguistics, one of the four fields of inquiry in anthropology, we examine format ties and the performance of humor as stylistic features of tribal focus groups and illustrate how linguistic devices can be used in analyzing aspects of adolescent and adult drinking. Focus group data require systematic review and analysis to identify useful findings that can lead to inquiry points to initiate collaborative work with local experts before the data can be developed and configured into effective program initiatives. C1 [Bletzer, Keith V.] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. [Yuan, Nicole P.; Koss, Mary P.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA. [Eaves, Emery R.] Univ Arizona, Dept Family & Community Med, Tucson, AZ USA. [Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Bletzer, KV (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA. EM keith.bletzer@asu.edu RI Reis, Aline/G-9573-2012; Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Bletzer, Keith/0000-0002-1782-6074 FU Intramural NIH HHS [Z01 AA000280-18]; NIAAA NIH HHS [K23 AA014606, K23AA014606, N01AA51012] NR 75 TC 1 Z9 1 U1 2 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0145-9740 J9 MED ANTHROPOL JI Med. Anthropol. PY 2011 VL 30 IS 3 BP 295 EP 318 AR PII 934439434 DI 10.1080/01459740.2011.560584 PG 24 WC Anthropology; Reproductive Biology; Social Sciences, Biomedical SC Anthropology; Reproductive Biology; Biomedical Social Sciences GA 764XK UT WOS:000290667700004 PM 21590583 ER PT J AU Rutter, CM Zaslavsky, AM Feuer, EJ AF Rutter, Carolyn M. Zaslavsky, Alan M. Feuer, Eric J. TI Dynamic Microsimulation Models for Health Outcomes: A Review SO MEDICAL DECISION MAKING LA English DT Review DE discrete event simulation; decision analytic models ID STOCHASTIC MICROPOPULATION MODELS; COST-EFFECTIVENESS ANALYSIS; PROSTATE-CANCER INCIDENCE; PREVENTION POLICY MODEL; OCCULT-BLOOD-TEST; COLORECTAL-CANCER; NATURAL-HISTORY; BREAST-CANCER; CERVICAL-CANCER; LUNG-CANCER AB Background. Microsimulation models (MSMs) for health outcomes simulate individual event histories associated with key components of a disease process; these simulated life histories can be aggregated to estimate population-level effects of treatment on disease outcomes and the comparative effectiveness of treatments. Although MSMs are used to address a wide range of research questions, methodological improvements in MSM approaches have been slowed by the lack of communication among modelers. In addition, there are few resources to guide individuals who may wish to use MSM projections to inform decisions. Methods. This article presents an overview of microsimulation modeling, focusing on the development and application of MSMs for health policy questions. The authors discuss MSM goals, overall components of MSMs, methods for selecting MSM parameters to reproduce observed or expected results (calibration), methods for MSM checking (validation), and issues related to reporting and interpreting MSM findings(sensitivity analyses, reporting of variability, and model transparency). Conclusions. MSMs are increasingly being used to provide information to guide health policy decisions. This increased use brings with it the need for both better understanding of MSMs by policy researchers, and continued improvement in methods for developing and applying MSMs. C1 [Rutter, Carolyn M.] Grp Hlth Res Inst, Biostat Unit, Seattle, WA USA. [Rutter, Carolyn M.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. [Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Feuer, Eric J.] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Rutter, CM (reprint author), 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. EM rutter.c@ghc.org FU NCI NIH HHS [U01 CA097427, U01 CA97427] NR 103 TC 40 Z9 40 U1 1 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-FEB PY 2011 VL 31 IS 1 BP 10 EP 18 DI 10.1177/0272989X10369005 PG 9 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 717CQ UT WOS:000287021000004 PM 20484091 ER PT S AU Choi, BY Muskett, J King, KA Zalewski, CK Shawker, T Reynolds, JC Butman, JA Brewer, CC Stewart, AK Alper, SL Griffith, AJ AF Choi, Byung Yoon Muskett, Julie King, Kelly A. Zalewski, Christopher K. Shawker, Thomas Reynolds, James C. Butman, John A. Brewer, Carmen C. Stewart, Andrew K. Alper, Seth L. Griffith, Andrew J. BE Alford, RL Sutton, VR TI Hereditary Hearing Loss with Thyroid Abnormalities SO MEDICAL GENETICS IN THE CLINICAL PRACTICE OF ORL SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID ENLARGED VESTIBULAR AQUEDUCT; GENOTYPE-PHENOTYPE CORRELATIONS; PENDRED-SYNDROME GENE; SYNDROME MOUSE MODEL; SLC26A4 GENE; CONGENITAL DEAFNESS; UNIQUE SPECTRUM; PDS MUTATIONS; DFNB4; CHILDREN AB Mutations in SLC26A4 can cause deafness and goiter in Pendred syndrome (PDS) or isolated non-syndromic enlargement of the vestibular aqueduct (NSEVA). PDS is one of the most common hereditary causes of deafness. It is characterized by autosomal-recessive inheritance of sensorineural hearing loss, enlarged vestibular aqueducts (EVA), and an iodide organification defect with or without goiter. The diagnosis is confirmed by detection of two mutant alleles of SLC26A4 in a patient with EVA. The perchlorate discharge test can detect the underlying thyroid biochemical defect and is useful for the evaluation of goiter or for the clinical diagnosis of PDS in a patient with a non-diagnostic SLC26A4 genotype. SLC26A4 encodes the pendrin polypeptide, an anion exchanger that, in recombinant expression systems, transports chloride, bicarbonate, and iodide. Investigation of pendrin function in the inner ear has been facilitated by the Slc26a4(Delta) (knockout) mouse model, but the exact mechanism of its hearing loss remains unclear, as does pendrin's principal transport function in the inner ear. Treatment of PDS is focused upon rehabilitation of hearing loss, and surveillance and management of goiter and, less commonly, hypothyroidism. Copyright (C) 2011 S. Karger AG, Basel C1 [Choi, Byung Yoon] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, NIH, Rockville, MD USA. [Muskett, Julie; King, Kelly A.; Zalewski, Christopher K.; Brewer, Carmen C.; Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD USA. [Shawker, Thomas; Butman, John A.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Reynolds, James C.] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. [Stewart, Andrew K.; Alper, Seth L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Griffith, AJ (reprint author), 5 Res Court,Room 2B-28, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 NR 63 TC 6 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9668-8 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2011 VL 70 BP 43 EP 49 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA BUD44 UT WOS:000288923700007 PM 21358184 ER PT S AU Friedman, TB Schultz, JM Ahmed, ZM Tsilou, ET Brewer, CC AF Friedman, Thomas B. Schultz, Julie M. Ahmed, Zubair M. Tsilou, Ekaterini T. Brewer, Carmen C. BE Alford, RL Sutton, VR TI Usher Syndrome: Hearing Loss with Vision Loss SO MEDICAL GENETICS IN THE CLINICAL PRACTICE OF ORL SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID SYNDROME TYPE-III; SENSORY HAIR-CELLS; NONSYNDROMIC DEAFNESS; RETINITIS-PIGMENTOSA; VISUAL IMPAIRMENT; RETINAL DISEASE; SYNDROME TYPE-1; ASHKENAZI JEWS; SYNDROME 1B; USH2A GENE AB Usher syndrome (USH) is a clinically heterogeneous condition characterized by sensorineural hearing loss, progressive retinal degeneration, and vestibular dysfunction. A minimum test battery is described as well as additional clinical evaluations that would provide comprehensive testing of hearing, vestibular function, and visual function in USH patients. USH is also genetically heterogeneous. At least nine genes have been identified with mutations that can cause USH. The proteins encoded by these genes are thought to interact with one another to form a network in the sensory cells of the inner ear and retina. Copyright (C) 2011 S. Karger AG, Basel C1 [Friedman, Thomas B.; Schultz, Julie M.] NIDCD, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. [Ahmed, Zubair M.] Cincinnati Childrens Hosp Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH USA. [Ahmed, Zubair M.] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH USA. [Tsilou, Ekaterini T.] NEI, Ophthalm Genet & Visual Funct Branch, Rockville, MD USA. [Brewer, Carmen C.] NIDCD, Otolaryngol Branch, NIH, Rockville, MD 20850 USA. RP Friedman, TB (reprint author), NIDCD, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Court,Rm 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [R00 DC009287] NR 50 TC 25 Z9 27 U1 0 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9668-8 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2011 VL 70 BP 56 EP 65 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA BUD44 UT WOS:000288923700009 PM 21358186 ER PT S AU Raygada, M Pasini, B Stratakis, CA AF Raygada, Margarita Pasini, Barbara Stratakis, Constantine A. BE Alford, RL Sutton, VR TI Hereditary Paragangliomas SO MEDICAL GENETICS IN THE CLINICAL PRACTICE OF ORL SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID FAMILIAL NONCHROMAFFIN PARAGANGLIOMAS; AUTOSOMAL-DOMINANT PARAGANGLIOMA; CAROTID-BODY TUMORS; CHROMOSOME 11Q23; IMPRINTED GENE; GLOMUS TUMORS; PHEOCHROMOCYTOMA; MUTATIONS; SUSCEPTIBILITY; SUPPRESSOR AB Paragangliomas (PGL) and pheochromocytomas (PCC) are rare, usually benign tumors that originate from the neuroendocrine tissue along the paravertebral axis. Up to 35% of these tumors may be hereditary; they are associated with germline mutations in genes encoding subunits of the succinate dehydrogenase (SDH) enzyme complex in the context of the familial PGL syndromes, PGL1, 3 and 4 caused by mutations in the SDHD, SDHC and SDHB genes, respectively. Another familial PGL syndrome, PGL2, is caused by mutations in SDHAF2/SDH5, which encodes for a molecule that is an accessory to the function of the SDH enzyme and its SDHA subunit. Less frequently, mutations in the genes responsible for Von Hippel Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN2), and neurofibromatosis type 1 (NF1) are also found in patients with hereditary PGL and PCC. Recently mutations were found in the SDHA subunit in a limited number of patients with PGL and/or PCC. The SDHB, SDHC and SDHD gene mutations (but not SDHA) can also be found in patients with PGL and/or PCC and gastrointestinal stromal tumors (GISTs), also known as the Carney-Stratakis syndrome; SDHB mutations, in particular, may also predispose to thyroid and renal cancer, and possibly other tumors. A new gene was recently found to predispose to PGL and/or PCC when mutated is TMEM127. In this text, we provide an overview of the genetics of PGLs and related conditions with an emphasis on genetic risk assessment, prevention, and prognosis. Copyright (C) 2011 S. Karger AG, Basel C1 [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Raygada, Margarita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin Genom, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HD999999] NR 38 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9668-8 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2011 VL 70 BP 99 EP 106 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BUD44 UT WOS:000288923700014 PM 21358191 ER PT S AU Wang, XJ Cutting, GR AF Wang, Xinjing Cutting, Garry R. BE Alford, RL Sutton, VR TI Chronic Rhinosinusitis SO MEDICAL GENETICS IN THE CLINICAL PRACTICE OF ORL SE Advances in Oto-Rhino-Laryngology LA English DT Article; Book Chapter ID PRIMARY CILIARY DYSKINESIA; COMMON VARIABLE IMMUNODEFICIENCY; ADULT CHRONIC RHINOSINUSITIS; ASPIRIN-SENSITIVE ASTHMA; ENDOSCOPIC SINUS SURGERY; CYSTIC-FIBROSIS; GENE-MUTATIONS; NASAL POLYPS; SYSTEMIC VASCULITIDES; INCREASED PREVALENCE AB Chronic rhinosinusitis (CRS) is a persistent inflammatory condition involving the nasal and paranasal mucosa. It is the most prevalent chronic condition in the United States. Sinonasal inflammation is also a common clinical presentation in a variety of systemic conditions. The etiology of CRS is complicated as a variety of extrinsic and intrinsic factors are frequently involved. Extrinsic factors include microbial infections that trigger abnormal immune responses. Intrinsic factors may predispose an individual to infection or exaggerated inflammatory responses. Several systemic conditions such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD), asthma, immunohyper-responsiveness, and immunodeficiencies illustrate the role of genetic abnormalities in the development of CRS. Both common and rare genetic variants have been found in an association with CRS. A role for genetic factors is also supported by the demonstration of CRS clustering in families. Although the majority of CRS cases are considered to be idiopathic, the pathological evidence suggests that the chronic condition could be an overlapped presentation of multiple underlying mechanisms. Systemic conditions may have an impact on the incidence, severity, prognosis, or treatment of patients with CRS. Evaluation for underlying conditions may help the otolaryngologist manage the symptoms of CRS and optimize therapy. Copyright (C) 2011 S. Karger AG, Basel C1 [Wang, Xinjing] NEI, NIH, Bethesda, MD 20892 USA. [Cutting, Garry R.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RP Wang, XJ (reprint author), NEI, NIH, 10 Ctr Dr,10D43, Bethesda, MD 20892 USA. EM wangx6@mail.nih.gov NR 75 TC 13 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0065-3071 BN 978-3-8055-9668-8 J9 ADV OTO-RHINO-LARYNG JI Adv.Otorhinolaryngol. PY 2011 VL 70 BP 114 EP 121 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BUD44 UT WOS:000288923700016 PM 21358193 ER PT J AU Schoenfeld, MP Ansari, RR Zakrajsek, JF Billiar, TR Toyoda, Y Wink, DA Nakao, A AF Schoenfeld, Michael P. Ansari, Rafat R. Zakrajsek, June F. Billiar, Timothy R. Toyoda, Yoshiya Wink, David A. Nakao, Atsunori TI Hydrogen therapy may reduce the risks related to radiation-induced oxidative stress in space flight SO MEDICAL HYPOTHESES LA English DT Article ID RICH WATER; ANTIOXIDANT; SPACEFLIGHT; MICE AB Cosmic radiation is known to induce DNA and lipid damage associated with increased oxidative stress and remains a major concern in space travel. Hydrogen, recently discovered as a novel therapeutic medical gas in a variety of biomedical fields, has potent antioxidant and anti-inflammatory activities. It is expected that space mission activities will increase in coming years both in numbers and duration. It is therefore important to estimate and prevent the risks encountered by astronauts due to oxidative stress prior to developing clinical symptoms of disease. We hypothesize that hydrogen administration to the astronauts by either inhalation or drinking hydrogen-rich water may potentially yield a novel and feasible preventative/therapeutic strategy to prevent radiation-induced adverse events. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Nakao, Atsunori] Univ Pittsburgh, Dept Surg, Med Ctr, Pittsburgh, PA 15213 USA. [Schoenfeld, Michael P.] NASA, George C Marshall Space Flight Ctr, Prop Res & Technol Branch, Huntsville, AL 35812 USA. [Ansari, Rafat R.; Zakrajsek, June F.] NASA, John H Glenn Res Ctr Lewis Field, Biosci & Technol Branch, Cleveland, OH USA. [Toyoda, Yoshiya; Nakao, Atsunori] Univ Pittsburgh, Dept Surg, Thomas E Starzl Transplantat Inst, Heart Lung & Esophageal Surg Inst, Pittsburgh, PA 15213 USA. [Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Nakao, A (reprint author), Univ Pittsburgh, Dept Surg, Med Ctr, E1551,Biomed Sci Tower, Pittsburgh, PA 15213 USA. EM anakao@imap.pitt.edu NR 15 TC 15 Z9 18 U1 0 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JAN PY 2011 VL 76 IS 1 BP 117 EP 118 DI 10.1016/j.mehy.2010.08.046 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 715VP UT WOS:000286918400028 PM 20851533 ER PT S AU Watt, JM Linguraru, MG Summers, RM AF Watt, Jeremy M. Linguraru, Marius George Summers, Ronald M. BE Weaver, JB Molthen, RC TI Affine Invariant Parameterization to Assess Local Shape in Abdominal Organs SO MEDICAL IMAGING 2011: BIOMEDICAL APPLICATIONS IN MOLECULAR, STRUCTURAL, AND FUNCTIONAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2011 - Biomedical Applications in Molecular, Structural, and Functional Imaging CY FEB 13-16, 2011 CL Lake Buena Vista, FL SP SPIE, Dynasil Corp/RMD Res, Amer Assoc Physicists Med (AAPM), DQE Instruments, Inc, Ocean Thin Films Inc, Coll Opt & Photon (CREOL), Univ Cent Florida, VIDA Diagnost, Inc DE Abdominal organs; shape analysis; 3D parameterization; affine invariance AB We present a novel method for three-dimensional (3D) shape parameterization. The approach is affine invariant and is applied to comparing local shape across abdominal organs. The inherent structure of the abdominal organs is used to generate a regular sampling of the organ's surface. 'Planar-convexity' is defined for a general 3D closed object as the property that there exists a set of parallel planes which cover the 3D space such that every intersection of a plane with the object is a singular closed planar curve. We show that this parameterization, combined with the 3D analogue of a 2D shape descriptor, successfully shown to be invariant under affine transformations and noise, can be effectively used to compare features of two closed 3D surfaces point-to-point. The technique avoids common problems with the parameterization of concave surfaces and shows great potential for analyzing and improving the automatic modeling and segmentation of abdominal organs. C1 [Watt, Jeremy M.; Linguraru, Marius George; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Watt, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM lingurarum@mail.nih.gov NR 11 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 978-0-81948-507-6 J9 PROC SPIE PY 2011 VL 7965 AR 79650F DI 10.1117/12.877589 PG 8 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BVF69 UT WOS:000291388700013 ER PT J AU George, AK Sonmez, M Lederman, RJ Faranesh, AZ AF George, Ashvin K. Sonmez, Merdim Lederman, Robert J. Faranesh, Anthony Z. TI Robust automatic rigid registration of MRI and X-ray using external fiducial markers for XFM-guided interventional procedures SO MEDICAL PHYSICS LA English DT Article DE X-ray; MRI; fiducial markers; localization; registration; fusion ID MAGNETIC-RESONANCE; PROSTATE BRACHYTHERAPY; SYSTEM; IMAGES; SEEDS; RECONSTRUCTION; LOCALIZATION; INTEGRATION; SWINE AB Purpose: In X-ray fused with MRI, previously gathered roadmap MRI volume images are overlaid on live X-ray fluoroscopy images to help guide the clinician during an interventional procedure. The incorporation of MRI data allows for the visualization of soft tissue that is poorly visualized under X-ray. The widespread clinical use of this technique will require fully automating as many components as possible. While previous use of this method has required time-consuming manual intervention to register the two modalities, in this article, the authors present a fully automatic rigid-body registration method. Methods: External fiducial markers that are visible under these two complimentary imaging modalities were used to register the X-ray images with the roadmap MR images. The method has three components: (a) The identification of the 3D locations of the markers from a full 3D MR volume, (b) the identification of the 3D locations of the markers from a small number of 2D X-ray fluoroscopy images, and (c) finding the rigid-body transformation that registers the two point sets in the two modalities. For part (a), the localization of the markers from MR data, the MR volume image was thresholded, connected voxels were segmented and labeled, and the centroids of the connected components were computed. For part (b), the X-ray projection images, produced by an image intensifier, were first corrected for distortions. Binary mask images of the markers were created from the distortion-corrected X-ray projection images by applying edge detection, pattern recognition, and image morphological operations. The markers were localized in the X-ray frame using an iterative backprojection-based method which segments voxels in the volume of interest, discards false positives based on the previously computed edge-detected projections, and calculates the locations of the true markers as the centroids of the clusters of voxels that remain. For part (c)MR, a variant of the iterative closest point method was used to find correspondences between and register the two sets of points computed from MR and X-ray data. This knowledge of the correspondence between the two point sets was used to refine, first, the X-ray marker localization and then the total rigid-body registration between modalities. The rigid-body registration was used to overlay the roadmap MR image onto the X-ray fluoroscopy projections. Results: In 35 separate experiments, the markers were correctly registered to each other in 100% of the cases. When half the number of X-ray projections was used (10 X-ray projections instead of 20), the markers were correctly registered in all 35 experiments. The method was also successful in all 35 experiments when the number of markers was (retrospectively) halved (from 16 to 8). The target registration error was computed in a phantom experiment to be less than 2.4 mm. In two in vivo experiments, targets (interventional devices with pointlike metallic structures) inside the heart were successfully registered between the two modalities. Conclusions: The method presented can be used to automatically register a roadmap MR image to X-ray fluoroscopy using fiducial markers and as few as ten X-ray projections. [DOI: 10.1118/1.3523621] C1 [George, Ashvin K.; Sonmez, Merdim; Lederman, Robert J.; Faranesh, Anthony Z.] NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Sonmez, Merdim] Bogazici Univ, Inst Biomed Engn, TR-34684 Istanbul, Turkey. RP Faranesh, AZ (reprint author), NHLBI, Translat Med Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. EM georgeak@nhlbi.nih.gov; faranesa@nhlbi.nih.gov OI lederman, robert/0000-0003-1202-6673 FU National Heart, Lung, and Blood Institute FX This work was supported by the intramural research program of the National Heart, Lung, and Blood Institute. The authors thank the following people for their help in collecting data and performing experiments: Israel Barbash, Jessica Colyer, Katherine Lucas, Kanishka Ratnayak, Bill Schenke, and Victor Wright. NR 40 TC 10 Z9 10 U1 0 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2011 VL 38 IS 1 BP 125 EP 141 DI 10.1118/1.3523621 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 700UM UT WOS:000285769800015 PM 21361182 ER PT J AU Jain, J Kumar, Y Sinha, R Kumar, R Stables, J AF Jain, Jainendra Kumar, Y. Sinha, Reema Kumar, Rajeev Stables, James TI Menthone Aryl Acid Hydrazones: A New Class of Anticonvulsants SO MEDICINAL CHEMISTRY LA English DT Article DE (+/-) 3-menthone; aryl acid hydrazone; anticonvulsant; MES; scPTZ; minimal clonic seizure; protective index (pI) ID ANTIEPILEPTIC DRUG DEVELOPMENT; SEMICARBAZONES; AGENTS AB A series of ten compounds (Compounds J(1)-J(10)) of (+/-) 3-menthone aryl acid hydrazone was synthesized and characterized by thin layer chromatography and spectral analysis. Synthesized compounds were evaluated for anticonvulsant activity after intraperitoneal (i.p) administration to mice by maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure method and minimal clonic seizure test. Minimal motor impairment was also determined for these compounds. Results obtained showed that four compounds out of ten afforded significant protection in the minimal clonic seizure screen at 6 Hz. Compound J(6), 4-Chloro-N-(2-isopropyl-5-methylcyclohexylidene) benzohydrazide was found to be the most active compound with MES ED(50) of 16.1 mg/kg and protective index (pI) of greater than 20, indicating that (+/-) 3-menthone aryl acid hydrazone possesses better and safer anticonvulsant properties than other reported menthone derivatives viz. menthone Schiff bases, menthone semicarbazides and thiosemicarbazides. C1 [Jain, Jainendra; Sinha, Reema; Kumar, Rajeev] RamEesh Inst Vocat & Tech Educ, Dept Pharm, Gautam Budh Nagar 201308, Uttar Pradesh, India. [Kumar, Y.] ITS Paramed Coll Pharm, Ghaziabad 201206, Uttar Pradesh, India. [Stables, James] NINDS, NIH, Bethesda, MD 20892 USA. RP Jain, J (reprint author), RamEesh Inst Vocat & Tech Educ, Dept Pharm, 3,Knowledge Pk 1, Gautam Budh Nagar 201308, Uttar Pradesh, India. EM jainendrem@yahoo.com NR 17 TC 8 Z9 8 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4064 J9 MED CHEM JI Med. Chem. PD JAN PY 2011 VL 7 IS 1 BP 56 EP 61 DI 10.2174/157340611794072689 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 706LX UT WOS:000286221000008 PM 21235520 ER PT J AU Oz, M Lorke, DE Hasan, M Petroianu, GA AF Oz, Murat Lorke, Dietrich E. Hasan, Mohammed Petroianu, George A. TI Cellular and Molecular Actions of Methylene Blue in the Nervous System SO MEDICINAL RESEARCH REVIEWS LA English DT Article DE methylene blue; nervous system; phenothiazines ID NITRIC-OXIDE SYNTHASE; PROLONGED POSTOPERATIVE DISORIENTATION; MANIC-DEPRESSIVE PSYCHOSIS; INTRACTABLE PRURITUS-ANI; ALZHEIMERS-DISEASE; MONOAMINE-OXIDASE; IN-VIVO; IFOSFAMIDE ENCEPHALOPATHY; PHENOTHIAZINE-DERIVATIVES; SEROTONIN TOXICITY AB Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide-induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. (C) 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 93-117, 2010 C1 [Oz, Murat] NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. [Oz, Murat; Hasan, Mohammed; Petroianu, George A.] UAE Univ, Dept Pharmacol, Fac Med & Hlth Sci, Al Ain, U Arab Emirates. [Lorke, Dietrich E.] UAE Univ, Dept Anat, Fac Med & Hlth Sci, Al Ain, U Arab Emirates. RP Oz, M (reprint author), NIDA, Integrat Neurosci Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 FU Intramural NIH HHS [NIH0011080950, Z01 DA000512-01] NR 236 TC 81 Z9 85 U1 3 U2 28 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD JAN PY 2011 VL 31 IS 1 BP 93 EP 117 DI 10.1002/med.20177 PG 25 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 703KA UT WOS:000285975600003 PM 19760660 ER PT B AU Hearing, VJ AF Hearing, Vincent J. BE Borovansky, J Riley, PA TI Genetics of Melanosome Structure and Function SO MELANINS AND MELANOSOMES: BIOSYNTHESIS, BIOGENESIS, PHYSIOLOGICAL, AND PATHOLOGICAL FUNCTIONS LA English DT Article; Book Chapter ID HERMANSKY-PUDLAK-SYNDROME; HUMAN SKIN PIGMENTATION; LYSOSOME-RELATED ORGANELLES; KERATINOCYTE GROWTH-FACTOR; GENERALIZED VITILIGO; MELANOCYTE DEVELOPMENT; ULTRAVIOLET-RADIATION; NEURAL CREST; IN-SITU; DISORDERS C1 NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Hearing, VJ (reprint author), NIH, Cell Biol Lab, 37 Convent Dr, Bethesda, MD 20892 USA. NR 84 TC 1 Z9 1 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PAPPELALLEE 3, W-69469 WEINHEIM, GERMANY BN 978-3-527-63614-3; 978-3-527-32892-5 PY 2011 BP 323 EP 341 D2 10.1002/9783527636150 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BA9TG UT WOS:000339835300012 ER PT S AU Bal, W Protas, AM Kasprzak, KS AF Bal, Wojciech Protas, Anna Maria Kasprzak, Kazimierz S. BE Sigel, A Sigel, H Sigel, RKO TI Genotoxicity of Metal Ions: Chemical Insights SO METAL IONS IN TOXICOLOGY: EFFECTS, INTERACTIONS, INTERDEPENDENCIES SE Metal Ions in Life Sciences LA English DT Article; Book Chapter DE arsenic; cadmium; carcinogenesis; chromium; genotoxicity; molecular mechanisms; nickel ID OXIDATIVE DNA-DAMAGE; OIL FLY-ASH; PARTICULATE NICKEL COMPOUNDS; C-TERMINAL TAIL; NUCLEOTIDE EXCISION-REPAIR; METHYLATED TRIVALENT ARSENICALS; MODEL LIPID HYDROPEROXIDES; PROSTATE EPITHELIAL-CELLS; CULTURED-MAMMALIAN-CELLS; PROTEIN CROSS-LINKING AB The purpose of this review is to provide a reader with a brief account of current results and views in the area of genotoxicity of metal ions, with a special attention to underlying chemical mechanisms. The text is divided into six sections. Following a general introduction in Section 1, Section 2 describes main molecular mechanisms of formation of genotoxic lesions: hydrolysis, alkylation, and radical reactions of nucleobases and the phosphosugar DNA backbone. The basics of cellular repair of DNA lesions are also shortly presented. This section serves as a background source for Sections 3, 4, and 5. Section 3 covers the main mechanisms of metal ion genotoxicity, followed by Section 4, which describes genotoxicity of individual metals; i.e., of the confirmed carcinogens As, Be, Cd, Cr, and Ni, as well as of the suspected carcinogens Co, Cu, Fe, Pb, Pt, and U-238 (also known as depleted uranium). The genotoxicity of exposures to metal mixtures is also discussed. Section 5 provides a critical overview of methodologies used for studying mutagenicity and carcinogenicity of metals; the final Section 6 summarizes the current state and future perspectives of research in genotoxic mechanisms of metal ions. C1 [Bal, Wojciech; Protas, Anna Maria] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. [Bal, Wojciech] Natl Res Inst, Cent Inst Labour Protect, PL-00701 Warsaw, Poland. [Kasprzak, Kazimierz S.] Natl Canc Inst, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Bal, W (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland. EM wbal@ibb.waw.pl; kasprzak@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 347 TC 17 Z9 20 U1 3 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1559-0836 BN 978-1-84973-091-4 J9 METAL IONS LIFE SCI PY 2011 VL 8 BP 319 EP 373 DI 10.1039/978184973211600319 PG 55 WC Chemistry, Applied; Chemistry, Inorganic & Nuclear; Toxicology SC Chemistry; Toxicology GA BSV56 UT WOS:000285938000013 PM 21473386 ER PT S AU Tokar, EJ Benbrahim-Tallaa, L Waalkes, MP AF Tokar, Erik J. Benbrahim-Tallaa, Lamia Waalkes, Michael P. BE Sigel, A Sigel, H Sigel, RKO TI Metal Ions in Human Cancer Development SO METAL IONS IN TOXICOLOGY: EFFECTS, INTERACTIONS, INTERDEPENDENCIES SE Metal Ions in Life Sciences LA English DT Article; Book Chapter DE arsenic; beryllium; cadmium; cancer; chromium; mechanisms; nickel ID INDUCED MALIGNANT-TRANSFORMATION; PROSTATE EPITHELIAL-CELLS; OXIDATIVE DNA-DAMAGE; DOUBLE KNOCKOUT MICE; MALE F344 RATS; DIMETHYLARSINIC ACID; GENE-EXPRESSION; CADMIUM CARCINOGENESIS; NEOPLASTIC LESIONS; LUNG-CANCER AB Metals have been in the environment during the entire evolution of man and the use of metals is key to human civilization. None-the-less, several very toxic species are included in the metallic elements and compounds either widely used by man and/or widely found in the human environment. This includes the five metallic agents considered human carcinogens, namely arsenic and arsenic compounds, beryllium and beryllium compounds, cadmium and cadmium compounds, chromium(VI) compounds, and nickel compounds, all of which are proven carcinogens in laboratory animals as well. There is significant human exposure to these carcinogenic inorganics, either occupationally, through the environment, or both. Inhalation is typical in the workplace while inhalation or ingestion occurs from environmental sources. Human metallic carcinogens frequently cause tumors at the portal of entry and lung cancers are the most common tumor after inhalation. Agent-specific tumors occur as well, like urinary bladder tumors after arsenic exposure, which are due to biokinetics or mechanisms that are specific to arsenic. Even in their simplest elemental form, metals are not inert, and they have biological activity. However, it should be kept in mind that these inorganic carcinogens, when in the atomic form, cannot be broken down into less toxic subunits, and this, in part, is why they are so important as environmental human carcinogens. This chapter focuses on the metallic agents that are known human carcinogens. C1 [Tokar, Erik J.; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. [Benbrahim-Tallaa, Lamia] Int Agcy Res Canc, IARC Monographs Sect, F-69372 Lyon, France. RP Tokar, EJ (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS NR 70 TC 20 Z9 21 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1559-0836 BN 978-1-84973-091-4 J9 METAL IONS LIFE SCI PY 2011 VL 8 BP 375 EP 401 DI 10.1039/978184973211600375 PG 27 WC Chemistry, Applied; Chemistry, Inorganic & Nuclear; Toxicology SC Chemistry; Toxicology GA BSV56 UT WOS:000285938000014 PM 21473387 ER PT J AU Lucas, HR Lee, JC AF Lucas, Heather R. Lee, Jennifer C. TI Copper(II) enhances membrane-bound alpha-synuclein helix formation SO METALLOMICS LA English DT Article ID PARKINSONS-DISEASE; BIOINORGANIC CHEMISTRY; SECONDARY STRUCTURE; EXTENDED HELIX; BINDING MODES; IN-VITRO; SPECTROSCOPY; VESICLES; FLUORESCENCE; AGGREGATION AB Interactions of copper and membranes with alpha-synuclein have been implicated in pathogenic mechanisms of Parkinson's disease, yet work examining both concurrently is scarce. We have examined the effect of copper(II) on protein/vesicle binding and found that both the copper(II) affinity and alpha-helical content are enhanced for the membrane-bound protein. C1 [Lucas, Heather R.; Lee, Jennifer C.] NHLBI, NIH, Lab Mol Biophys, Bethesda, MD 20892 USA. RP Lee, JC (reprint author), NHLBI, NIH, Lab Mol Biophys, Bldg 10, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU National Institutes of Health, National Heart, Lung, and Blood Institute FX Supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. We also acknowledge Dr Duck-Yeon Lee (Biochemistry Core Facility) and Dr Grzegorz Piszczek (Biophysical Facility) for technical assistance. NR 39 TC 11 Z9 11 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1756-5901 J9 METALLOMICS JI Metallomics PY 2011 VL 3 IS 3 BP 280 EP 283 DI 10.1039/c0mt00088d PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 731RE UT WOS:000288126200008 PM 21290070 ER PT S AU Hallmans, G Vaught, JB AF Hallmans, Goran Vaught, Jimmie B. BE Dillner, J TI Best Practices for Establishing a Biobank SO METHODS IN BIOBANKING SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Biobank; Biological resource center; Specimen; Liquid nitrogen; Biological sample; Cryovials; Bar code ID BIOSPECIMEN OWNERSHIP; QUALITY; STORAGE AB A biobank may be defined as the long-term storage of biological samples for research or clinical purposes. In addition to storage facilities, a biobank may comprise a complete organization with biological samples, data, personnel, policies, and procedures for handling specimens and performing other services, such as the management of the database and the planning of scientific studies. This combination of facilities, policies, and processes may also be called a biological resource center (BRC) (www.iarc.fr). Research using specimens from biobanks is regulated by European Union (EU) recommendations (Recommendations on Research on Human Biological Materials. The draft recommendation on research on human biological materials was approved by CDBI at its plenary meeting on 20 October 2005) and by voluntary best practices from the U.S. National Cancer Institute (NCI) (http://biospecimens.cancer.gov) and other organizations. Best practices for the management of research biobanks vary according to the institution and differing international regulations and standards. However, there arc many areas of agreement that have resulted in best practices that should be followed in order to establish a biobank for the custodianship of high-quality specimens and data. C1 [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Vaught, Jimmie B.] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. RP Hallmans, G (reprint author), Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. NR 27 TC 18 Z9 20 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-995-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 675 BP 241 EP 260 DI 10.1007/978-1-59745-423-0_13 D2 10.1007/978-1-59745-423-0 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BRV86 UT WOS:000283764300013 PM 20949394 ER PT B AU Phinney, S Crane, NJ Gage, FA Gorbach, AM Elster, EA AF Phinney, Samuel Crane, Nicole J. Gage, Frederick A. Gorbach, Alexander M. Elster, Eric A. BE Uygun, K Lee, CY TI Use of Optical Imaging and Spectroscopy in Assessment of Organ Perfusion SO METHODS IN BIOENGINEERING: ORGAN PRESERVATION AND REENGINEERING SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE imaging; infrared imaging (IR); organ perfusion; three-charged coupled device (3-CCD); visible reflectance imaging system (VRIS); ischemia/reperfusion injury; renal transplantation; pump perfusion ID VISIBLE-LIGHT SPECTROSCOPY; IN-VIVO; OXYGEN-SATURATION; INTRAOPERATIVE ASSESSMENT; DIFFUSE-REFLECTANCE; PULSATILE PERFUSION; TISSUE PERFUSION; RENAL-ALLOGRAFTS; NITRIC-OXIDE; BLOOD-FLOW AB We present procedures to use imaging to assess organ perfusion in an ischemia/reperfusion injury model in the intraoperative and organ procurement setting, in particular, on pump perfusion. These technologies, namely 3-CCD, IR, and VRIS imaging, use the spectral signatures of kidneys to determine tissue oxygenation and perfusion. This information not only correlates directly with the physiology of organ perfusion but can be provided in a clinically useful, real-time format. Utilization of the technologies in tandem for quantitative assessment of organ viability is discussed. C1 [Crane, Nicole J.; Gage, Frederick A.; Elster, Eric A.] USN, Dept Regenerat Med, Operat & Undersea Med Directorate, Med Res Ctr, Silver Spring, MD 20910 USA. [Phinney, Samuel] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. [Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. [Elster, Eric A.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. RP Elster, EA (reprint author), USN, Dept Regenerat Med, Operat & Undersea Med Directorate, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM eric.elster1@med.navy.mil NR 27 TC 0 Z9 0 U1 0 U2 2 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-60807-013-8 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2011 BP 137 EP 159 PG 23 WC Cell & Tissue Engineering; Engineering, Biomedical; Transplantation SC Cell Biology; Engineering; Transplantation GA BVN87 UT WOS:000292008900008 ER PT S AU Subramanian, P Crawford, SE Becerra, SP AF Subramanian, Preeti Crawford, Susan E. Becerra, S. Patricia BE Whisstock, JC Bird, PI TI ASSAYS FOR THE ANTIANGIOGENIC AND NEUROTROPHIC SERPIN PIGMENT EPITHELIUM-DERIVED FACTOR SO METHODS IN ENZYMOLOGY: BIOLOGY OF SERPINS SE Methods in Enzymology LA English DT Review; Book Chapter ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; FACTOR PEDF; BINDING-SITE; INTERPHOTORECEPTOR MATRIX; BOVINE EYES; EXPRESSION; NEURONS; CELLS; NEUROPROTECTION; OVEREXPRESSION AB Pigment epithelium-derived factor (PEDF) is a secreted serpin that exhibits a variety of interesting biological activities. The multifunctional PEDF has neurotrophic and antiangiogenic properties, and acts in retinal differentiation, survival, and maintenance. It is also antitumorigenic and antimetastatic, and has stem cell self-renewal properties. It is widely distributed in the human body and exists in abundance in the eye as a soluble extracellular glycoprotein. Its levels are altered in diseases characterized by retinopathies and angiogenesis. Its mechanisms of neuroprotection and angiogenesis are associated with receptor interactions at cell-surface interfaces and changes in protein expression. This serpin lacks demonstrable serine protease inhibitory activity, but has binding affinity to extracellular matrix components and cell-surface receptors. Here we describe purification protocols, methods to quantify PEDF, and determine interactions with specific molecules, as well as neurotrophic and angiogenesis assays for this multifunctional protein. C1 [Subramanian, Preeti; Becerra, S. Patricia] NEI, Sect Prot Struct & Funct, NIH, Bethesda, MD 20892 USA. [Crawford, Susan E.] NorthShore Univ Res Inst, Dept Surg & Pathol, Evanston, IL USA. RP Subramanian, P (reprint author), NEI, Sect Prot Struct & Funct, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA EY000306-16] NR 44 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-386471-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2011 VL 499 BP 183 EP 204 DI 10.1016/B978-0-12-386471-0.00010-9 PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BVZ34 UT WOS:000293200200010 PM 21683255 ER PT J AU Cimino, JJ AF Cimino, J. J. TI High-quality, Standard, Controlled Healthcare Terminologies Come of Age SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material ID LANGUAGE; SYSTEM C1 NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Cimino, JJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM ciminoj@cc.nih.gov OI Cimino, James/0000-0003-4101-1622 FU Intramural NIH HHS [Z99 CL999999] NR 21 TC 11 Z9 12 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2011 VL 50 IS 2 BP 101 EP 104 PG 4 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 743IG UT WOS:000289011300001 PM 21416108 ER PT J AU Lin, MC Vreeman, DJ McDonald, CJ Huff, SM AF Lin, M. C. Vreeman, D. J. McDonald, C. J. Huff, S. M. TI A Characterization of Local LOINC Mapping for Laboratory Tests in Three Large Institutions SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Controlled vocabulary; LOINC; evaluation research; clinical laboratory information systems ID OBSERVATION IDENTIFIER NAMES; CODES LOINC; TERMINOLOGICAL SYSTEMS AB Objectives: We characterized the use of laboratory LOINC (R) codes in three large institutions, focused on the following questions: 1) How many local codes had been voluntarily mapped to LOINC codes by each institution? 2) Could additional mappings be found by expert manual review for any local codes that were not initially mapped to LOINC codes by the local institution? and 3) Are there any common characteristics of unmapped local codes that might explain why some local codes were not mapped to LOINC codes by the local institution? Methods: With Institutional Review Board (IRB) approval, we obtained deidentified data from three large institutions. We calculated the percentage of local codes that have been mapped to LOINC by personnel at each of the institutions. We also analyzed a sample of unmapped local codes to determine whether any additional LOINC mappings could be made and identify common characteristics that might explain why some local codes did not have mappings. Results: Concept type coverage and concept token coverage (volume of instance data covered) of local codes mapped to LOINC codes were 0.44/0.59, 0.78/0.78 and 0.79/0.88 for ARUP, Intermountain, and Regenstrief, respectively. After additional expert manual mapping, the results showed mapping rates of 0.63/0.72, 0.83/0.80 and, 0.88/0.90, respectively. After excluding local codes which were not useful for inter-institutional data exchange, the mapping rates became 0.73/0.79, 0.90/0.99 and 0.93/0.997, respectively. Conclusions: Local codes for two institutions could be mapped to LOINC codes with 99% or better concept token coverage, but mapping for a third institution (a reference laboratory) only achieved 79% concept token coverage. Our research supports the conclusions of others that not all local codes should be assigned LOINC codes. There should also be public discussions to develop more precise rules for when LOINC codes should be assigned C1 [Lin, M. C.; Huff, S. M.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. [Vreeman, D. J.] Regenstrief Inst Inc, Indianapolis, IN USA. [Vreeman, D. J.] Indiana Univ Sch Med, Indianapolis, IN USA. [McDonald, C. J.] Natl Lib Med, Lister Hill Ctr, Washington, DC USA. [Huff, S. M.] Intermt Healthcare, Salt Lake City, UT USA. RP Huff, SM (reprint author), S Off Bldg,5171 S Cottonwood St, Murray, UT 84107 USA. EM stan.huff@imail.org FU Intramural NIH HHS [Z99 LM999999] NR 22 TC 17 Z9 17 U1 1 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2011 VL 50 IS 2 BP 105 EP 114 DI 10.3414/ME09-01-0072 PG 10 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 743IG UT WOS:000289011300002 PM 20725694 ER PT J AU McCray, AT Gefeller, O Aronsky, D Leong, TY Sarkar, IN Bergemann, D Lindberg, DAB van Bemmel, JH Haux, R AF McCray, A. T. Gefeller, O. Aronsky, D. Leong, T. Y. Sarkar, I. N. Bergemann, D. Lindberg, D. A. B. van Bemmel, J. H. Haux, R. TI The Birth and Evolution of a Discipline Devoted to Information in Biomedicine and Health Care As Reflected in its Longest Running Journal SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Methods of Information in Medicine; medical informatics; biomedical informatics; health informatics ID INTERNIST-1/QMR KNOWLEDGE BASE; ELECTRONIC MEDICAL RECORD; PROBABILISTIC DIAGNOSIS; ECG INTERPRETATION; DECISION-SUPPORT; SYSTEMS; PERFORMANCE; LANGUAGE; MODEL; CLASSIFICATION AB Background: The journal Methods of Information in Medicine, founded in 1962, has now completed its 50th volume. Its publications during the last five decades reflect the formation of a discipline that deals with information in biomedicine and health care. Objectives: To report about 1) the journal's origin, 2) the individuals who have significantly contributed to it, 3) trends in the journal's aims and scope, 4) influential papers and 5) major topics published in Methods over the years. Methods: Methods included analysing the correspondence and journal issues in the archives of the editorial office and of the publisher, citation analysis using the ISI and Scopus databases, and analysing the articles' Medical Subject Headings (MeSH) in MEDLINE. Results: In the journal's first 50 years 208 editorial board members and/or editors contributed to the journal's development, with most individuals coming from Europe and North America. The median time of service was 11 years. At the time of analysis 2,456 articles had been indexed with MeSH. Topics included computerized systems of various types, informatics methodologies, and topics related to a specific medical domain. Some MeSH topic entries were heavily and regularly represented in each of the journal's five decades (e.g. information systems and medical records), while others were important in a particular decade, but not in other decades (e.g. punched-card systems and systems integration). Seven papers were cited more than 100 times and these also covered a broad range of themes such as knowledge representation, analysis of biomedical data and knowledge, clinical decision support and electronic patient records. Conclusions: Methods of Information in Medicine is the oldest international journal in biomedical informatics. The journal's development over the last 50 years correlates with the formation of this new discipline. It has and continues to stress the basic methodology and scientific fundamentals of organizing, representing and analysing data, information and knowledge in biomedicine and health care. It has and continues to stimulate multi-disciplinary communication on research that is devoted to high-quality, efficient health care, to quality of life and to the progress of biomedicine and the health sciences. C1 [McCray, A. T.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Gefeller, O.] Univ Erlangen Nurnberg, Inst Med Informat Biometry & Epidemiol, Nurnberg, Germany. [Aronsky, D.] Vanderbilt Univ, Dept Biomed Informat & Emergency Med, Nashville, TN USA. [Leong, T. Y.] Natl Univ Singapore, Dept Comp Sci, Singapore, Singapore. [Sarkar, I. N.] Univ Vermont, Dept Microbiol & Mol Genet, Ctr Clin & Translat Sci, Burlington, VT 05405 USA. [Sarkar, I. N.] Dept Comp Sci, Burlington, VT USA. [Bergemann, D.] Schattauer Verlag, Stuttgart, Germany. [Lindberg, D. A. B.] Natl Lib Med, Bethesda, MD USA. [van Bemmel, J. H.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. [Haux, R.] Tech Univ Carolo Wilhelmina Braunschweig, Inst Technol, Braunschweig, Germany. [Haux, R.] Hannover Med Sch, Peter L Reichertz Inst Med Informat, Hannover, Germany. RP McCray, AT (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, 10 Shattuck St, Boston, MA 02115 USA. EM alexa_mccray@hms.harvard.edu RI LEONG, Tze Yun/H-1142-2015; OI Gefeller, Olaf/0000-0002-8985-7582 NR 86 TC 17 Z9 19 U1 1 U2 8 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2011 VL 50 IS 6 BP 491 EP 507 DI 10.3414/ME11-06-0001 PG 17 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 872UF UT WOS:000298834500002 PM 22146913 ER PT J AU Mitchell, JA Gerdin, U Lindberg, DAB Lovis, C Martin-Sanchez, FJ Miller, RA Shortliffe, EH Leong, TY AF Mitchell, J. A. Gerdin, U. Lindberg, D. A. B. Lovis, C. Martin-Sanchez, F. J. Miller, R. A. Shortliffe, E. H. Leong, T. -Y. TI 50 Years of Informatics Research on Decision Support: What's Next SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Decision support; standard vocabularies; information retrieval; genomic and clinical information; integrative system; knowledge representation; personalized medicine; education ID PERSONALIZED MEDICINE; DIAGNOSTIC ERRORS; COMPUTER; SYSTEMS; GENOME; AGE AB Objectives: To reflect on the history, status, and future trends of decision support in health and biomedical informatics. To highlight the new challenges posed by the complexity and diversity of genomic and clinical domains. To examine the emerging paradigms for supporting cost-effective, personalized decision making. Methods: A group of international experts in health and biomedical informatics presented their views and discussed the challenges and issues on decision support at the Methods of Information in Medicine 50th anniversary symposium. The experts were invited to write short articles summarizing their thoughts and positions after the symposium. Results and Conclusions: The challenges posed by the complexity and diversity of the domain knowledge, system, infrastructure, and usage pattern are highlighted. New requirements and computational paradigms for representing, using, and acquiring biomedical knowledge and healthcare protocols are proposed. The underlying common themes identified for developing next-generation decision, support include incorporating lessons from history, uniform vocabularies, integrative interfaces, contextualized decisions, personalized recommendations, and adaptive solutions. C1 [Mitchell, J. A.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA. [Gerdin, U.] Nat Board Hlth & Welfare Regulat & Licenses Termi, Stockholm, Sweden. [Lindberg, D. A. B.] Natl Lib Med, Bethesda, MD USA. [Lovis, C.] Univ Hosp Geneva, Geneva, Switzerland. [Martin-Sanchez, F. J.] Univ Melbourne, Melbourne, Vic, Australia. [Miller, R. A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Shortliffe, E. H.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Leong, T. -Y.] Natl Univ Singapore, Singapore, Singapore. RP Mitchell, JA (reprint author), Univ Utah, Dept Biomed Informat, 26 S 2000 E HSEB 5700, Salt Lake City, UT 84112 USA. EM joyce.mitchell@hsc.utah.edu RI Lovis, Christian/D-2634-2012; LEONG, Tze Yun/H-1142-2015; Martin-Sanchez, Fernando/A-7587-2008 OI Lovis, Christian/0000-0002-2681-8076; Martin-Sanchez, Fernando/0000-0002-7312-5707 FU National Center for Research resources [UL1-RR025764]; National Library of Medicine [LM007124]; ARUP Institute for Clinical and Experimental pathology; Department of Biomedical Informatics at the University of Utah; Clinical Genetics Institute at Intermountain Healthcare; U.S. National Library of Medicine [1R01 LM010828-01] FX The authors drafted individual sections of this article based on their contributions at the Symposium: Section 2 (Shortliffe), Section 3 (Leong), Section 4 (Martin-Sanchez), Section 5 (Mitchell), Section 6 (Gerdin), Section 7 (Lovis), Section 8 (Miller), Section 9 (Lindberg). Joyce Mitchell drafted and revised the integrated paper. Tze-Yun Leong wrote the structured abstract and edited the integrated paper. Dr. Mitchell's work is supported by grants UL1-RR025764 from the National Center for Research resources, LM007124 from the National Library of Medicine, the ARUP Institute for Clinical and Experimental pathology, the Department of Biomedical Informatics at the University of Utah, and the Clinical Genetics Institute at Intermountain Healthcare. Dr. Miller's work is supported in part by a grant from the U.S. National Library of Medicine, 1R01 LM010828-01. NR 39 TC 10 Z9 10 U1 2 U2 5 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2011 VL 50 IS 6 BP 525 EP 535 DI 10.3414/ME11-06-0004 PG 11 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 872UF UT WOS:000298834500004 PM 22146915 ER PT J AU Fukuma, A Kurosaki, Y Morikawa, Y Grolla, A Feldmann, H Yasuda, J AF Fukuma, Aiko Kurosaki, Yohei Morikawa, Yuko Grolla, Allen Feldmann, Heinz Yasuda, Jiro TI Rapid detection of Lassa virus by reverse transcription-loop-mediated isothermal amplification SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE detection; Lassa virus; RT-LAMP ID POLYMERASE CHAIN-REACTION; MASTOMYS-NATALENSIS; DENGUE VIRUS; FEVER; ASSAY; DIAGNOSIS; RNA; PCR; EBOLA AB In this study, a simple one-step reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection of Lassa virus (LASV) was established. The two primer sets were designed to detect LASV circulating in Sierra Leone and northeastern Nigeria. The RT-LAMP assay using these primer sets was able to detect 100 copies of the in vitro transcribed artificial LASV RNA within 25 min. The assay was also evaluated using intact viral RNA extracted from cell culture-propagated viruses and confirmed to be highly specific for LASV. The RT-LAMP assay developed in this study is rapid, simple, and highly specific for the detection of LASV, although its sensitivity is slightly lower than that of real-time RT-PCR. In addition, because the RT-LAMP assay does not require the use of sophisticated equipment, it would be advantageous for clinical diagnosis of LASV infection in developing countries. It might also be employed in cases of deliberate release during bioterrorism attacks or in epidemiological surveillance for disease outbreaks. C1 [Fukuma, Aiko; Kurosaki, Yohei; Yasuda, Jiro] Natl Res Inst Police Sci, Dept Forens Sci 1, Kashiwa, Chiba 2770882, Japan. [Fukuma, Aiko; Kurosaki, Yohei; Yasuda, Jiro] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan. [Fukuma, Aiko; Morikawa, Yuko] Kitasato Univ, Kitasato Inst Life Sci, Tokyo 1088641, Japan. [Fukuma, Aiko; Morikawa, Yuko] Kitasato Univ, Grad Sch Infect Control, Tokyo 1088641, Japan. [Grolla, Allen; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada. [Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, Rocky Mt Labs, Hamilton, MT USA. RP Yasuda, J (reprint author), Nagasaki Univ, Dept Emerging Infect Dis, Inst Trop Med, 1-12-4 Sakamoto, Nagasaki 8528523, Japan. EM j-yasuda@nagasaki-u.ac.jp FU Ministry of Health, Labor and Welfare of Japan; Japan Society for the Promotion of Science; Japan Science and Technology Agency FX This work was supported by grants from the Ministry of Health, Labor and Welfare of Japan, the Japan Society for the Promotion of Science, and the Japan Science and Technology Agency. NR 24 TC 5 Z9 6 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PD JAN PY 2011 VL 55 IS 1 BP 44 EP 50 DI 10.1111/j.1348-0421.2010.00286.x PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA 700RJ UT WOS:000285761700006 PM 21175773 ER PT J AU Navarathna, DHMLP Das, A Morschhauser, J Nickerson, KW Roberts, DD AF Navarathna, Dhammika H. M. L. P. Das, Aditi Morschhaeuser, Joachim Nickerson, Kenneth W. Roberts, David D. TI Dur3 is the major urea transporter in Candida albicans and is co-regulated with the urea amidolyase Dur1,2 SO MICROBIOLOGY-SGM LA English DT Article ID SACCHAROMYCES-CEREVISIAE; NITROGEN-METABOLISM; MOUSE MODEL; ASPERGILLUS-NIDULANS; HELICOBACTER-PYLORI; CYTOKINE EXPRESSION; NUTRITIONAL CONTROL; HEME OXYGENASE; GENE; HEMOGLOBIN AB Hemiascomycetes, including the pathogen Candida albicans, acquire nitrogen from urea using the urea amidolyase Dun,2, whereas all other higher fungi use primarily the nickel-containing urease. Urea metabolism via Dun,2 is important for resistance to innate host immunity in C. albicans infections. To further characterize urea metabolism in C. albicans we examined the function of seven putative urea transporters. Gene disruption established that Dur3, encoded by orf 19.781, is the predominant transporter. [C-14]Urea uptake was energy-dependent and decreased approximately sevenfold in a dur3 Delta mutant. DUR1,2 and DUR3 expression was strongly induced by urea, whereas the other putative transporter genes were induced less than twofold. Immediate induction of DUR3 by urea was independent of its metabolism via Dun 2, but further slow induction of DUR3 required the Dun,2 pathway. We investigated the role of the GATA transcription factors Gat1 and Gln3 in DUR1,2 and DUR3 expression. Urea induction of DUR1,2 was reduced in a gat1 Delta mutant, strongly reduced in a gln3 Delta mutant, and abolished in a gat1 Delta gln3 Delta double mutant. In contrast, DUR3 induction by urea was preserved in both single mutants but reduced in the double mutant, suggesting that additional signalling mechanisms regulate DUR3 expression. These results establish Dur3 as the major urea transporter in C. albicans and provide additional insights into the control of urea utilization by this pathogen. C1 [Navarathna, Dhammika H. M. L. P.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Das, Aditi; Morschhaeuser, Joachim] Univ Wurzburg, Inst Mol Infekt Biol, Wurzburg, Germany. [Nickerson, Kenneth W.] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Morschhauser, Joachim/E-2918-2013 OI Roberts, David/0000-0002-2481-2981; Morschhauser, Joachim/0000-0003-4227-8687 FU National Institutes of Health (NIH), NCI, Center for Cancer Research; Deutsche Forschungsgemeinschaft (DFG) [MO 846/4]; University of Nebraska; John C. and Nettie V. David Memorial Trust; Ann L. Kelsall and the Farnesol and Candida albicans Research Fund FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), NCI, Center for Cancer Research (D. D. R.). Work in J.M.'s laboratory was supported by the Deutsche Forschungsgemeinschaft (DFG; grant MO 846/4). Work in K. W. N.'s laboratory was supported by the University of Nebraska Tobacco Settlement Biomedical Research Enhancement Fund, the John C. and Nettie V. David Memorial Trust Fund, Ann L. Kelsall and the Farnesol and Candida albicans Research Fund. NR 38 TC 12 Z9 24 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JAN PY 2011 VL 157 BP 270 EP 279 DI 10.1099/mic.0.045005-0 PN 1 PG 10 WC Microbiology SC Microbiology GA 712FJ UT WOS:000286649800027 PM 20884691 ER PT B AU Ji, JF Wang, XW AF Ji, Junfang Wang, Xin Wei BE Cho, WCS TI MicroRNAs in Hepatocellular Carcinoma SO MICRORNAS IN CANCER TRANSLATIONAL RESEARCH LA English DT Article; Book Chapter ID NON-TUMOROUS TISSUES; LIVER-CANCER; GENE-EXPRESSION; DOWN-REGULATION; UP-REGULATION; SUPPRESSES TUMORIGENICITY; REGULATES EXPRESSION; MICROARRAY ANALYSIS; NUCLEAR EXPORT; CELL-MIGRATION AB Hepatocellular carcinoma (HCC) is a major type of liver cancer. It is the third leading cause of cancer-related death worldwide. MicroRNAs (miRNAs), a class of small non-coding RNAs, are aberrantly expressed in HCC. The genomic instability, transcriptionally regulation, and epigenetic alteration have been identified to contribute to the abnormal expression of miRNAs in HCC. Moreover, deregulation of miRNAs not only functionally enables liver tumorigenesis, but also promotes tumor progression. Further, aberrant expression of certain miRNAs is correlated with clinical features of HCC, indicating their potential to serve as diagnostic and prognostic biomarkers of HCC. Several miRNAs have been validated in independent cohorts as HCC biomarkers, paving the way for developing clinically useful platforms to aid in diagnosis and prognosis for patients, and to assist in HCC patient stratification with the potential for personalized adjuvant therapy. In addition, several oncogenic and tumor suppressive miRNAs are being exploited as possible therapeutic targets in HCC. In this chapter, recent studies on miRNA and HCC, particularly those that are clinically relevant, are discussed. C1 [Ji, Junfang; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. EM jijun@mail.nig.gov; xw3u@nih.gov NR 106 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-94-007-0297-4 PY 2011 BP 163 EP 188 DI 10.1007/978-94-007-0298-1_7 D2 10.1007/978-94-007-0298-1 PG 26 WC Oncology SC Oncology GA BTS52 UT WOS:000287980500007 ER PT B AU Minton, AP Rivas, G AF Minton, Allen P. Rivas, German BE Luisi, PL Stano, P TI Biochemical Reactions in the Crowded and Confined Physiological Environment: Physical Chemistry Meets Synthetic Biology SO MINIMAL CELL: THE BIOPHYSICS OF CELL COMPARTMENT AND ORIGIN OF CELL FUNCTIONALITY LA English DT Article; Book Chapter ID EXCLUDED SURFACE-AREA; PROTEIN FIBER FORMATION; SICKLE-CELL-DISEASE; ESCHERICHIA-COLI; SELF-ASSOCIATION; MACROMOLECULAR STRUCTURE; GLOBULAR-PROTEINS; ALPHA-SYNUCLEIN; MOLECULAR CONFINEMENT; POLY(ETHYLENE GLYCOL) C1 [Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Rivas, German] CSIC, Ctr Invest Biol, Chem & Phys Biol Program, Madrid, Spain. RP Minton, AP (reprint author), NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM minton@helix.nig.gov; grivas@cib.csic.es OI Rivas, German/0000-0003-3450-7478 NR 77 TC 2 Z9 2 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-90-481-9943-3 PY 2011 BP 73 EP 89 DI 10.1007/978-90-481-9944-0_5 D2 10.1007/978-90-481-9944-0 PG 17 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA BSJ84 UT WOS:000284731100005 ER PT B AU Cleland, MM Youle, RJ AF Cleland, Megan M. Youle, Richard J. BE Lu, B TI Mitochondrial Dynamics and Apoptosis SO MITOCHONDRIAL DYNAMICS AND NEURODEGENERATION LA English DT Article; Book Chapter DE Mitochondrial dynamics; Apoptosis; Mitofusin; OPA 1; Drp 1 ID CYTOCHROME-C RELEASE; DEPENDENT PROTEIN-KINASE; DOMINANT OPTIC ATROPHY; PROGRAMMED CELL-DEATH; WD REPEAT PROTEIN; M-AAA PROTEASE; MAMMALIAN-CELLS; OUTER-MEMBRANE; ENDOPLASMIC-RETICULUM; PEROXISOMAL FISSION AB The dynamic nature of mitochondria is not only important for maintaining normal healthy cells, but is also very important in the timely execution of apoptosis. The machinery involved in mediating mitochondrial fission and fusion, namely the large GTPases Drp 1, OPA 1, Mfn 1 and Mfn2, can be modulated to either intensify or reduce apoptosis. During the intrinsic/mitochondrial apoptotic pathway, Drp 1 promotes mitochondrial fragmentation, while proteolytic cleavage and release of OPA 1 from the mitochondria enhances this fragmentation and results in a swollen/ altered cristae morphology. Conditions that enhance mitochondrial fusion, such as overexpression of OPA 1, Mfn 1, Mfn2 or inhibition of Drp 1, generally result in a delay of apoptosis while enhancing mitochondrial fission, through overexpression of Drp 1 or down regulating OPA 1, Mfn 1 or Mfn2, augments apoptosis. C1 [Cleland, Megan M.; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr,MSC 3704,Bldg 35 Rm,2C917, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov NR 176 TC 1 Z9 2 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-94-007-1290-4 PY 2011 BP 109 EP 138 DI 10.1007/978-94-007-1291-1_4 D2 10.1007/978-94-007-1291-1 PG 30 WC Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BVG86 UT WOS:000291502600004 ER PT B AU Cai, Q Sheng, ZH AF Cai, Qian Sheng, Zu-Hang BE Lu, B TI Mitochondrial Dynamics and Axonal Transport SO MITOCHONDRIAL DYNAMICS AND NEURODEGENERATION LA English DT Article; Book Chapter DE Mitochondria; Axonal transport; Docking; Synaptic plasticity; Kinesin; Motor adaptor; Anterograde transport; Retrograde transport; Stationary mitochondria; Mitochondrial mobility ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; CULTURED HIPPOCAMPAL-NEURONS; MEMBRANOUS ORGANELLES INVIVO; KINESIN-ASSOCIATED PROTEIN; LIGHT-CHAIN TCTEX-1; NERVE GROWTH-FACTOR; BRAIN MYOSIN-V; CYTOPLASMIC DYNEIN; IN-VITRO AB Mitochondria are essential organelles for neuronal survival and function through ATP generation, calcium buffering, and apoptotic signaling. Due to their extreme polarity, neurons utilize specialized mechanisms to regulate mitochondrial transport along axons to areas in which energy production and calcium homeostasis are in high demand, namely, active growth cones, nodes of Ranvier, and synaptic terminals. Axonal mitochondria display complex mobility patterns and undergo saltatory and bidirectional movement. While one-third of axonal mitochondria are mobile, the rest remains stationary. Docked mitochondria serve as local power plants and maintain local Ca2+ homeostasis. The balance between mobile and stationary mitochondria is influenced by the diverse physiological states of axons and synapses. The coordination of mitochondrial mobility by axonal physiology is crucial for neuronal development and synaptic function. Defects in mitochondrial transport have been implicated in the pathologic processes of several major neuro-degenerative diseases. Thus, understanding the regulation of axonal mitochondrial transport will increase our knowledge of fundamental processes that may affect human neurological disorders. In this chapter, we introduce recent advances in our understanding of motor-adaptor complexes and docking machinery that mediate mitochondria] transport and axonal distribution. We will also discuss the molecular mechanisms underlying the complex mobility patterns of axonal mitochondria and how mitochondrial mobility impacts the physiology and function of synapses. C1 [Cai, Qian; Sheng, Zu-Hang] Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, NIH, Bethesda, MD 20892 USA. RP Sheng, ZH (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, NIH, Bldg 35,Room 2B-215,35 Convent Dr, Bethesda, MD 20892 USA. EM shengz@ninds.nih.gov NR 127 TC 1 Z9 1 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-94-007-1290-4 PY 2011 BP 139 EP 168 DI 10.1007/978-94-007-1291-1_5 D2 10.1007/978-94-007-1291-1 PG 30 WC Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BVG86 UT WOS:000291502600005 ER PT J AU Gaal, J Stratakis, CA Carney, JA Ball, ER Korpershoek, E Lodish, MB Levy, I Xekouki, P van Nederveen, FH den Bakker, MA O'Sullivan, M Dinjens, WNM de Krijger, RR AF Gaal, Jose Stratakis, Constantine A. Carney, J. Aidan Ball, Evan R. Korpershoek, Esther Lodish, Maya B. Levy, Isaac Xekouki, Paraskevi van Nederveen, Francien H. den Bakker, Michael A. O'Sullivan, Maureen Dinjens, Winand N. M. de Krijger, Ronald R. TI SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors SO MODERN PATHOLOGY LA English DT Article DE Carney-Stratakis syndrome; Carney triad; gastrointestinal stromal tumor; immunohistochemistry; SDHB ID GERMLINE MUTATIONS; GENE-MUTATIONS; PARAGANGLIOMA; SUCCINATE; PHEOCHROMOCYTOMA; ANGIOGENESIS; EXPRESSION; STOMACH AB Mutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. However, other tumors have been associated with SDHx mutations, such as gastrointestinal stromal tumors (GISTs) specifically in the context of Carney-Stratakis syndrome. Previously, we have shown that SDHB immunohistochemistry is a reliable technique for the identification of pheochromocytomas and paragangliomas caused by SDHx mutations. We hypothesized that GISTs in patients with SDHx mutations would be negative immunohistochemically for SDHB as well. Four GISTs from patients with Carney-Stratakis syndrome and six from patients with Carney triad were investigated by SDHB immunohistochemistry. Five GISTs with KIT or PDGFRA gene mutations were used as controls. In addition, SDHB immunohistochemistry was performed on 42 apparently sporadic GISTs. In cases in which the SDHB immunohistochemistry was negative, mutational analysis of SDHB, SDHC, and SDHD was performed. All GISTs from patients with Carney-Stratakis syndrome and Carney triad were negative for SDHB immunohistochemically. In one patient with Carney-Stratakis syndrome, a germline SDHB mutation was found (p.Ser92Thr). The five GISTs with a KIT or PDGFRA gene mutation were all immunohistochemically positive for SDHB. Of the 42 sporadic tumors, one GIST was SDHB-negative. Mutational analysis of this tumor did not reveal an SDHx mutation. All SDHB-negative GISTs were located in the stomach, had an epithelioid morphology, and had no KIT or PDGFRA mutations. We show that Carney-Stratakis syndrome-and Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT-or PDGFRA-mutated GISTs and a majority of sporadic GISTs. We suggest that GISTs of epithelioid cell morphology are tested for SDHB immunohistochemically. In case of negative SDHB staining in GISTs, Carney-Stratakis syndrome or Carney triad should be considered and appropriate clinical surveillance should be instituted. Modern Pathology (2011) 24, 147-151; doi:10.1038/modpathol.2010.185; published online 1 October 2010 C1 [Gaal, Jose; Korpershoek, Esther; van Nederveen, Francien H.; den Bakker, Michael A.; Dinjens, Winand N. M.; de Krijger, Ronald R.] Univ Med Ctr Rotterdam, Erasmus MC, Josephine Nefkens Inst, Dept Pathol, NL-3000 CA Rotterdam, Netherlands. [Stratakis, Constantine A.; Ball, Evan R.; Lodish, Maya B.; Levy, Isaac; Xekouki, Paraskevi] NIH, Sect Endocrinol & Genet, Pediat Endocrinol Training Program, Dev Endocrinol Branch, Bethesda, MD 20892 USA. [Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [O'Sullivan, Maureen] Trinity Coll Dublin, Sch Med, Dept Pathol, Dublin, Ireland. [O'Sullivan, Maureen] Our Ladys Childrens Hosp, Natl Childrens Res Ctr, Dublin, Ireland. RP Gaal, J (reprint author), Univ Med Ctr Rotterdam, Erasmus MC, Josephine Nefkens Inst, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM j.gaal@erasmusmc.nl FU Eunice Kennedy Shriver National Institute of Child Health & Human Development; Erasmus MC FX We thank Frank van der Panne for assistance with preparation of the figure. This work was supported in part by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development. The work described in this article was supported by a grant from Erasmus MC. NR 17 TC 83 Z9 90 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2011 VL 24 IS 1 BP 147 EP 151 DI 10.1038/modpathol.2010.185 PG 5 WC Pathology SC Pathology GA 702BG UT WOS:000285868900016 PM 20890271 ER PT S AU Iyer, LM Abhiman, S Aravind, L AF Iyer, Lakshminarayan M. Abhiman, Saraswathi Aravind, L. BE Cheng, XD Blumenthal, RM TI Natural History of Eukaryotic DNA Methylation Systems SO MODIFICATIONS OF NUCLEAR DNA AND ITS REGULATORY PROTEINS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID DE-NOVO METHYLATION; RESTRICTION-MODIFICATION SYSTEMS; BASE EXCISION-REPAIR; CYTOSINE METHYLTRANSFERASE HOMOLOG; BACTERIUM DEINOCOCCUS RADIODURANS; PHAGE BETA-GLUCOSYLTRANSFERASE; MODIFICATION GENE-COMPLEX; DOMAIN-CONTAINING PROTEIN; ZYGOTIC PATERNAL GENOME; RNA-BINDING DOMAIN AB Methylation of cytosines and adenines in DNA is a widespread epigenetic mark in both prokaryotes and eukaryotes. In eukaryotes, it has a profound influence on chromatin structure and dynamics. Recent advances in genomics and biochemistry have considerably elucidated the functions and provenance of these DNA modifications. DNA methylases appear to have emerged first in bacterial restriction-modification (R-M) systems from ancient RNA-modifying enzymes, in transitions that involved acquisition of novel catalytic residues and DNA-recognition features. DNA adenine methylases appear to have been acquired by ciliates, heterolobosean amoeboflagellates, and certain chlorophyte algae. Six distinct clades of cytosine methylases, including the DNMT1, DNMT2, and DNMT3 clades, were acquired by eukaryotes through independent lateral transfer of their precursors from bacteria or bacteriophages. In addition to these, multiple adenine and cytosine methylases were acquired by several families of eukaryotic transposons. In eukaryotes, the DNA-methylase module was often combined with distinct modified and unmodified peptide recognition domains and other modules mediating specialized interactions, for example, the RFD module of DNMT1 which contains a permuted Sm domain linked to a helix-turn-helix domain. In eukaryotes, the evolution of DNA methylases appears to have proceeded in parallel to the elaboration of histone-modifying enzymes and the RNAi system, with functions related to counter-viral and counter-transposon defense, and regulation of DNA repair and differential gene expression being their primary ancestral functions. Diverse DNA demethylation systems that utilize base-excision repair via DNA glycosylases and cytosine deaminases appear to have emerged in multiple eukaryotic lineages. Comparative genomics suggests that the link between cytosine methylation and DNA glycosylases probably emerged first in a novel R M system in bacteria. Recent studies suggest that the 5mC is not a terminal DNA modification, with enzymes of the Tet/JBP family of 2-oxoglutarate- and iron-dependent dioxygenases further hydroxylating it to form 5-hydroxy-methylcytosine (5hmC). These enzymes emerged first in bacteriophages and appear to have been transferred to eukaryotes on one or more occasions. Eukaryotes appear to have recruited three major types of DNA-binding domains (SRA/SAD, TAM/MBD, and CXXC) in discriminating DNA with methylated or unmethylated cytosines. Analysis of the domain architectures of these domains and the DNA methylases suggests that early in eukaryotic evolution they developed a close functional link with SET-domain methylases and Jumonji-related demethylases that operate on peptides in chromatin proteins. In several eukaryotes, other functional connections were elaborated in the form of various combinations between domains related to DNA methylation and those involved in ATP-dependent chromatin remodeling and RNAi. In certain eukaryotes, such as mammals and angiosperms, novel dependencies on the DNA methylation system emerged, which resulted in it affecting unexpected aspects of the biology of these organisms such as parent offspring interactions. In genomic terms, this was reflected in the emergence of new proteins related to methylation, such as Stella. The well-developed methylation systems of certain heteroloboseans, stramenopiles, chlorophytes, and haptophyte indicate that these might be new model systems to explore the relevance of DNA modifications in eukaryotes. C1 [Iyer, Lakshminarayan M.; Abhiman, Saraswathi; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Iyer, LM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 280 TC 51 Z9 55 U1 8 U2 48 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-387685-0 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2011 VL 101 BP 25 EP 104 DI 10.1016/B978-0-12-387685-0.00002-0 PG 80 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BUS52 UT WOS:000290238400002 PM 21507349 ER PT S AU Aravind, L Abhiman, S Iyer, LM AF Aravind, L. Abhiman, Saraswathi Iyer, Lakshminarayan M. BE Cheng, XD Blumenthal, RM TI Natural History of the Eukaryotic Chromatin Protein Methylation System SO MODIFICATIONS OF NUCLEAR DNA AND ITS REGULATORY PROTEINS SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID SET DOMAIN METHYLTRANSFERASE; RNA-POLYMERASE-II; LINKED MENTAL-RETARDATION; LYSINE DEMETHYLASE LSD1; E3 UBIQUITIN LIGASE; ARGININE METHYLATION; COMPARATIVE GENOMICS; STRUCTURAL BASIS; CRYSTAL-STRUCTURE; HETEROCHROMATIN FORMATION AB In eukaryotes, methylation of nucleosomal histones and other nuclear proteins is a central aspect of chromatin structure and dynamics. The past 15 years have seen an enormous advance in our understanding of the biochemistry of these modifications, and of their role in establishing the epigenetic code. We provide a synthetic overview, from an evolutionary perspective, of the main players in the eukaryotic chromatin protein methylation system, with an emphasis on catalytic domains. Several components of the eukaryotic protein methylation system had their origins in bacteria. In particular, the Rossmann fold protein methylases (PRMTs and DOT1), and the LSD1 and jumonji-related demethylases and oxidases, appear to have emerged in the context of bacterial peptide methylation and hydroxylation systems. These systems were originally involved in synthesis of peptide secondary metabolites, such as antibiotics, toxins, and siderophores. The peptidylarginine deiminases appear to have been acquired by animals from bacterial enzymes that modify cell-surface proteins. SET domain methylases, which display the beta-clip fold, apparently first emerged in prokaryotes from the SAF superfamily of carbohydrate-binding domains. However, even in bacteria, a subset of the SET domains might have evolved a chromatin-related role in conjunction with a BAF60a/b-like SWIB domain protein and topoisomerases. By the time of the last eukaryotic common ancestor, multiple SET and PRMT methylases were already in place and are likely to have mediated methylation at the H3K4, H3K9, H3K36, and H4K20 positions, and carried out both asymmetric and symmetric arginine dimethylation. Inference of H3K27 methylation in the ancestral eukaryote appears uncertain, though it was certainly in place a little later in eukaryotic evolution. Current data suggest that unlike SET methylases, which are universally present in eukaryotes, demethylases are not. They appear to be absent in the earliest-branching eukaryotic lineages, and emerged later along with several other chromatin proteins, such as the Dot1-methylase, prior to divergence of the kinetoplastid-heterolobosean lineage from the remaining eukaryotes. This period also corresponds to the point of origin of DNA cytosine methylation by DNMT1. Origin of major lineages of SET domains such as the Trithorax, Su(var)3-9, Ash1, SMYD, and TTLL12 and E(Z) might have played the initial role in the establishment of multiple distinct heterochromatic and euchromatic states that are likely to have been present, in some form, through much of eukaryotic evolution. Elaboration of these chromatin states might have gone hand-in-hand with acquisition of multiple jumonji-related and LSD1-like demethylases, and functional linkages with the DNA methylation and RNAi systems. Throughout eukaryotic evolution, there were several lineage-specific expansions of SET domain proteins, which might be related to a special transcription regulation process in trypanosomes, acquisition of new meiotic recombination hotspots in animals, and methylation and associated modifications of the diatom silaffin proteins involved in silica biomineralization. The use of specific domains to "read" the methylation marks appears to have been present in the ancestral eukaryote itself Of these the chromo-like domains appear to have been acquired from bacterial secreted proteins that might have a role in binding cell-surface peptides or peptidoglycan. Domain architectures of the primary enzymes involved in the eukaryotic protein methylation system indicate key features relating to inteactions with each other and other modifications in chromatin, such as acetylation. They also emphasize the profound functional distinction between the role of demethylation and deacetylation in regulation of chromatin dynamics. C1 [Aravind, L.; Abhiman, Saraswathi; Iyer, Lakshminarayan M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 267 TC 34 Z9 35 U1 1 U2 34 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-387685-0 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2011 VL 101 BP 105 EP 176 DI 10.1016/B978-0-12-387685-0.00004-4 PG 72 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BUS52 UT WOS:000290238400003 PM 21507350 ER PT J AU Cervenka, I Wolf, J Masek, J Krejci, P Wilcox, WR Kozubik, A Schulte, G Gutkind, JS Bryja, V AF Cervenka, Igor Wolf, Joshua Masek, Jan Krejci, Pavel Wilcox, William R. Kozubik, Alois Schulte, Gunnar Gutkind, J. Silvio Bryja, Vitezslav TI Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WNT RECEPTOR ACTIVATION; BETA-CATENIN; CORECEPTOR LRP6; PATHWAY; GSK3-BETA; MECHANISM; BINDING; CELLS; INACTIVATION; TRANSDUCTION AB LDL-related protein 6 (LRP6) is a coreceptor of WNTs and a key regulator of the WNT/beta-catenin pathway. Upon activation, LRP6 is phosphorylated within its intracellular PPPS/TP motifs. These phosphorylated motifs are required to recruit axin and to inhibit glycogen synthase kinase 3 (GSK3), two basic components of the beta-catenin destruction complex. On the basis of a kinome-wide small interfering RNA (siRNA) screen and confirmative biochemical analysis, we show that several proline-directed mitogen-activated protein kinases (MAPKs), such as p38, ERK1/2, and JNK1 are sufficient and required for the phosphorylation of PPPS/TP motifs of LRP6. External stimuli, which control the activity of MAPKs, such as phorbol esters and fibroblast growth factor 2 (FGF2) control the choice of the LRP6-PPPS/TP kinase and regulate the amplitude of LRP6 phosphorylation and WNT/beta-catenin-dependent transcription. Our findings suggest that cells not only recruit one dedicated LRP6 kinase but rather select their LRP6 kinase depending on cell type and the external stimulus. Moreover, direct phosphorylation of LRP6 by MAPKs provides a unique point for convergence between WNT/beta-catenin signaling and mitogenic pathways. C1 [Cervenka, Igor; Masek, Jan; Krejci, Pavel; Kozubik, Alois; Bryja, Vitezslav] Masaryk Univ, Fac Sci, Inst Expt Biol, CZ-61137 Brno, Czech Republic. [Wolf, Joshua; Gutkind, J. Silvio] NIH, Oral & Pharyngeal Canc Branch, Cell Growth Regulat Sect, Bethesda, MD 20892 USA. [Wolf, Joshua; Gutkind, J. Silvio] NIH, Mol Carcinogenesis Unit, Bethesda, MD 20892 USA. [Cervenka, Igor; Krejci, Pavel; Kozubik, Alois; Bryja, Vitezslav] Acad Sci Czech Republic, Inst Biophys, Dept Cytokinet, CS-61265 Brno, Czech Republic. [Wilcox, William R.] Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. [Krejci, Pavel; Wilcox, William R.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Schulte, Gunnar] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Bryja, V (reprint author), Masaryk Univ, Fac Sci, Inst Expt Biol, Kotlarska 2, CZ-61137 Brno, Czech Republic. EM gutkind@dir.nidcr.nih.gov; bryja@sci.muni.cz RI Gutkind, J. Silvio/A-1053-2009; Kozubik, Alois/H-1954-2014; Krejci, Pavel/I-4285-2014; Bryja, Vit?zslav/H-1925-2014; Masek, Jan/I-9029-2014; OI Bryja, Vit?zslav/0000-0002-9136-5085; Krejci, Pavel/0000-0003-0618-9134 FU Czech Science Foundation [204/09/0498, 204/09/J030, 204/09/H058, 301/09/0587]; EMBO; Ministry of Education Youth and Sports of the Czech Republic [MSM 0021622430]; Academy of Sciences of the Czech Republic [AVOZ50040507, AVOZ50040702]; Karolinska Institutet; Swedish Medical Research Council [K2008-68P-20810-01-4, K2008-68X-20805-01-4]; Knut and Alice Wallenberg Foundation; Swedish Cancer Foundation; Swedish Foundation for the International Cooperation in Research and Higher Education (STINT); National Institutes of Health [NIH 5P01HD022657-21A]; Intramural Program; National Institute of Dental and Craniofacial Research; Howard Hughes Medical Institute FX This study was supported by grants from the Czech Science Foundation (204/09/0498, 204/09/J030, 204/09/H058, 301/09/0587; V.B. and P.K.), the EMBO Installation Grant (V.B.), and the Ministry of Education Youth and Sports of the Czech Republic (MSM 0021622430; V.B.); by the Academy of Sciences of the Czech Republic (AVOZ50040507, AVOZ50040702); and by grants from the Karolinska Institutet, the Swedish Medical Research Council (K2008-68P-20810-01-4, K2008-68X-20805-01-4), the Knut and Alice Wallenberg Foundation, the Swedish Cancer Foundation, the Swedish Foundation for the International Cooperation in Research and Higher Education (STINT) (G.S.), the National Institutes of Health (NIH 5P01HD022657-21A; W.R.W.), the Intramural Program, the National Institute of Dental and Craniofacial Research (J.W. and J.S.G.), and the Howard Hughes Medical Institute Research Scholars Program (J.W.). NR 36 TC 44 Z9 48 U1 0 U2 6 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 2011 VL 31 IS 1 BP 179 EP 189 DI 10.1128/MCB.00550-10 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 691PP UT WOS:000285093600014 PM 20974802 ER PT S AU Roullet, FI Crawley, JN AF Roullet, Florence I. Crawley, Jacqueline N. BE Hagan, JJ TI Mouse Models of Autism: Testing Hypotheses About Molecular Mechanisms SO MOLECULAR AND FUNCTIONAL MODELS IN NEUROPSYCHIATRY SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Autism; Behavior; Candidate genes; Communication; Genetics; Mice; Mouse models; Olfactory; Repetitive; Social; Vocalization ID FRAGILE-X-SYNDROME; FETAL VALPROATE SYNDROME; SOCIAL APPROACH BEHAVIORS; FMR1 KNOCKOUT MICE; HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; SCENT MARKING BEHAVIOR; BTBR-T+TF/J MICE; ULTRASONIC VOCALIZATIONS; SPECTRUM DISORDERS AB Autism is a neurodevelopmental disorder that is currently diagnosed by the presence of three behavioral criteria (1) qualitative impairments in reciprocal social interactions, (2) deficits in communication, including delayed language and noninteractive conversation, and (3) motor stereotypies, repetitive behaviors, insistence on sameness, and restricted interests. This chapter describes analogous behavioral assays that have been developed for mice, including tests for social approach, reciprocal social interactions, olfactory communication, ultrasonic vocalizations, repetitive and perseverative behaviors, and motor stereotypies. Examples of assay applications to genetic mouse models of autism are provided. Robust endophenotypes that are highly relevant to the core symptoms of autism are enabling the search for the genetic and environmental causes of autism, and the discovery of effective treatments. C1 [Roullet, Florence I.; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. RP Roullet, FI (reprint author), NIMH, Lab Behav Neurosci, Intramural Res Program, Bldg 35,Room 1C-903-909,Mail Code 3730, Bethesda, MD 20892 USA. EM firoullet@gmail.com; crawleyj@mail.nih.gov FU Intramural NIH HHS [ZIA MH002179-26] NR 187 TC 23 Z9 24 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-19702-4 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2011 VL 7 BP 187 EP 212 DI 10.1007/7854_2010_113 D2 10.1007/978-3-642-19703-1 PG 26 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BVF17 UT WOS:000291364600007 PM 21225409 ER PT J AU Wills, S Rossi, CC Bennett, J Cerdeno, VM Ashwood, P Amaral, DG Van de Water, J AF Wills, Sharifia Rossi, Christy C. Bennett, Jeffrey Cerdeno, Veronica Martinez Ashwood, Paul Amaral, David G. Van de Water, Judy TI Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism SO MOLECULAR AUTISM LA English DT Article AB Background: Autism is a neurodevelopmental disorder characterized by impairments in social interaction and deficits in verbal and nonverbal communication, together with the presence of repetitive behaviors or a limited repertoire of activities and interests. The causes of autism are currently unclear. In a previous study, we determined that 21% of children with autism have plasma autoantibodies that are immunoreactive with a population of neurons in the cerebellum that appear to be Golgi cells, which are GABAergic interneurons. Methods: We have extended this analysis by examining plasma immunoreactivity in the remainder of the brain. To determine cell specificity, double-labeling studies that included one of the calcium-binding proteins that are commonly colocalized in GABAergic neurons (calbindin, parvalbumin or calretinin) were also carried out to determine which GABAergic neurons are immunoreactive. Coronal sections through the rostrocaudal extent of the macaque monkey brain were reacted with plasma from each of seven individuals with autism who had previously demonstrated positive Golgi cell staining, as well as six negative controls. In addition, brain sections from adult male mice were similarly examined. Results: In each case, specific staining was observed for neurons that had the morphological appearance of interneurons. By double-labeling sections with plasma and with antibodies directed against g-aminobutyric acid (GABA), we determined that all autoantibody-positive neurons were GABAergic. However, not all GABAergic neurons were autoantibody-positive. Calbindin was colabeled in several of the autoantibody-labeled cells, while parvalbumin colabeling was less frequently observed. Autoantibody-positive cells rarely expressed calretinin. Sections from the mouse brain processed similarly to the primate sections also demonstrated immunoreactivity to interneurons distributed throughout the neocortex and many subcortical regions. Some cell populations stained in the primate (such as the Golgi neurons in the cerebellum) were not as robustly immunoreactive in the mouse brain. Conclusions: These results suggest that the earlier report of autoantibody immunoreactivity to specific cells in the cerebellum extend to other regions of the brain. Further, these findings confirm the autoantibody-targeted cells to be a subpopulation of GABAergic interneurons. The potential impact of these autoantibodies on GABAergic disruption with respect to the etiology of autism is discussed herein. C1 [Wills, Sharifia; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Rossi, Christy C.; Bennett, Jeffrey; Cerdeno, Veronica Martinez; Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Ctr Neurosci, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Ashwood, Paul] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Rossi, Christy C.; Bennett, Jeffrey; Cerdeno, Veronica Martinez; Ashwood, Paul; Amaral, David G.; Van de Water, Judy] Univ Calif Davis Med Ctr, MIND Inst, Sacramento, CA 95817 USA. [Wills, Sharifia; Ashwood, Paul; Van de Water, Judy] Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Davis, CA 95616 USA. RP Van de Water, J (reprint author), Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, 451 Hlth Sci Dr,Suite 6510 GBSF, Davis, CA 95616 USA. EM javandewater@ucdavis.edu FU National Institute of Environmental Health Sciences [1 P01 ES11269]; US Environmental Protection Agency through the Science to Achieve Results program [R829388]; National Institutes of Health [MH41479]; National Alliance for Research on Schizophrenia and Depression; M.I.N.D. Institute; Cure Autism Now FX This work was supported by National Institute of Environmental Health Sciences grant 1 P01 ES11269, the US Environmental Protection Agency through the Science to Achieve Results program (grant R829388), Cure Autism Now, National Institutes of Health grant MH41479, the National Alliance for Research on Schizophrenia and Depression, and the M.I.N.D. Institute. We also thank the study participants and their families for their contribution to this study. NR 80 TC 21 Z9 21 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2040-2392 J9 MOL AUTISM JI Mol. Autism PY 2011 VL 2 AR 5 DI 10.1186/2040-2392-2-5 PG 14 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA V30IF UT WOS:000208809000005 PM 21521495 ER PT J AU Szczesniak, MW Ciomborowska, J Nowak, W Rogozin, IB Makalowska, I AF Szczesniak, Michal W. Ciomborowska, Joanna Nowak, Witold Rogozin, Igor B. Makalowska, Izabela TI Primate and Rodent Specific Intron Gains and the Origin of Retrogenes with Splice Variants SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE intron gain; gene structure evolution; splice variant; RNF113; DCAF12 ID MESSENGER-RNA; EVOLUTION; GENE; POSITIONS; CHROMOSOME; SEQUENCE; FAMILY AB Retroposition, a leading mechanism for gene duplication, is an important process shaping the evolution of genomes. Retrogenes are also involved in the gene structure evolution as a major player in the process of intron deletion. Here, we demonstrate the role of retrogenes in intron gain in mammals. We identified one case of "intronization," the transformation of exonic sequences into an intron, in the primate specific retrogene RNF113B and two independent "intronization" events in the retrogene DCAF12L2, one in the common ancestor of primates and rodents and another one in the rodent lineage. Intron gain resulted from the origin of new splice variants, and both genes have two transcript forms, one with retained intron and one with the intron spliced out. Evolution of these genes, especially RNF113B, has been very dynamic and has been accompanied by several additional events including parental gene loss, secondary retroposition, and exaptation of transposable elements. C1 [Szczesniak, Michal W.; Ciomborowska, Joanna; Makalowska, Izabela] Adam Mickiewicz Univ Poznan, Fac Biol, Lab Bioinformat, Poznan, Poland. [Nowak, Witold] Adam Mickiewicz Univ Poznan, Fac Biol, Lab Mol Tech, Poznan, Poland. [Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Makalowska, I (reprint author), Adam Mickiewicz Univ Poznan, Fac Biol, Lab Bioinformat, Poznan, Poland. EM izabel@amu.edu.pl FU National Library of Medicine at National Institutes of Health/U.S. Department of Health and Human Services FX We thank Jurgen Brosius and two reviewers for their comments and insightful suggestions. I.B.R. was supported by the Intramural Research Program of the National Library of Medicine at National Institutes of Health/U.S. Department of Health and Human Services. NR 28 TC 21 Z9 21 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JAN PY 2011 VL 28 IS 1 BP 33 EP 37 DI 10.1093/molbev/msq260 PG 5 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 696CD UT WOS:000285418600008 PM 20889727 ER PT J AU Yuan, CQ Rao, RP Jesmin, N Bamba, T Nagashima, K Pascual, A Preat, T Fukusaki, E Acharya, U Acharya, JK AF Yuan, Changqing Rao, Raghavendra Pralhada Jesmin, Nahid Bamba, Takeshi Nagashima, Kunio Pascual, Alberto Preat, Thomas Fukusaki, Eiichiro Acharya, Usha Acharya, Jairaj K. TI CDase is a pan-ceramidase in Drosophila SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SPHINGOLIPID METABOLISM; ALKALINE CERAMIDASE; SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION; MOLECULAR MACHINERY; CLONING; MELANOGASTER; TRAFFICKING; ENZYMES; SPHINGOSINE AB Ceramidases catalyze the conversion of ceramide to sphingosine. They are acylaminohydrolases that catalyze the deacylation of the amide-linked saturated fatty acid from ceramide to generate sphingosine. They also catalyze the reverse reaction of ceramide biosynthesis using sphingosine and fatty acid. In mammals, different proteins catalyze these reactions while individually exhibiting optimal activity over a narrow pH range and have been accordingly called acid, neutral, and alkaline ceramidases. Several genes encode for variants of alkaline ceramidase in mammals. Brainwashing (Bwa) is the only putative alkaline ceramidase homologue present in Drosophila. In this study we have demonstrated that BWA does not exhibit ceramidase activity and that bwa null mutants display no loss of ceramidase activity. Instead, the neutral ceramidase gene CDase encodes the protein that is responsible for all measurable ceramidase activity in Drosophila. Our studies show strong genetic interaction of Bwa with CDase and the Drosophila ceramide kinase gene (DCERK). We show that, although BWA is unlikely to be a ceramidase, it is a regulator of sphingolipid flux in Drosophila. Bwa exhibits strong genetic interaction with other genes coding for ceramide-metabolizing enzymes. This interaction might partly explain its original identification as a ceramidase. C1 [Yuan, Changqing; Rao, Raghavendra Pralhada; Acharya, Jairaj K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. [Jesmin, Nahid; Acharya, Usha] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. [Bamba, Takeshi; Fukusaki, Eiichiro] Osaka Univ, Grad Sch Engn, Dept Biotechnol, Suita, Osaka 5650871, Japan. [Nagashima, Kunio] SAIC, EM Facil Image Anal Lab, Frederick, MD 21702 USA. [Pascual, Alberto; Preat, Thomas] Ecole Super Phys & Chim Ind Ville Paris, CNRS, Neurobiol Unit, F-75005 Paris, France. RP Acharya, JK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA. EM acharyaj@mail.nih.gov RI Pascual, Alberto/E-9609-2015; IBIS, NEURONAL/O-9910-2015; IBIS, NEUROBIOLOGIA/O-9922-2015; OI Pascual, Alberto/0000-0001-5459-6207; Preat, Thomas/0000-0001-9976-1763 FU National Cancer Institute; National Institutes of Health [RO1EY16469]; National Institutes of Health, Department of Health and Human Services FX We thank Shyam Sharan and Ira Daar for critical reading of the manuscript. Jun Yonekubo (Nihon Waters K.K.) is thanked for his helpful discussion and support for the experiments. This work was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Work in Usha Acharya's laboratory was supported by a grant from the National Institutes of Health (RO1EY16469). We thank Alicja Biewalska, Director of the Shared Lipidomic Resources at the Medical University of South Carolina, for providing us with [3H]C16- and C24-ceramide. NR 38 TC 5 Z9 5 U1 0 U2 3 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 1 PY 2011 VL 22 IS 1 BP 33 EP 43 DI 10.1091/mbc.E10-05-0453 PG 11 WC Cell Biology SC Cell Biology GA 703FF UT WOS:000285962300004 PM 21148295 ER PT J AU Bond, LM Peden, AA Kendrick-Jones, J Sellers, JR Buss, F AF Bond, Lisa M. Peden, Andrew A. Kendrick-Jones, John Sellers, James R. Buss, Folma TI Myosin VI and its binding partner optineurin are involved in secretory vesicle fusion at the plasma membrane SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID ADRENAL CHROMAFFIN CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; TO-GOLGI TRANSPORT; CATECHOLAMINE RELEASE; PROTEIN-TRANSPORT; MAMMALIAN-CELLS; SNARE COMPLEX; F-ACTIN; EXOCYTOSIS; PORE AB During constitutive secretion, proteins synthesized at the endoplasmic reticulum (ER) are transported to the Golgi complex for processing and then to the plasma membrane for incorporation or extracellular release. This study uses a unique live-cell constitutive secretion assay to establish roles for the molecular motor myosin VI and its binding partner optineurin in discrete stages of secretion. Small interfering RNA-based knockdown of myosin VI causes an ER-to-Golgi transport delay, suggesting an unexpected function for myosin VI in the early secretory pathway. Depletion of myosin VI or optineurin does not affect the number of vesicles leaving the trans-Golgi network (TGN), indicating that these proteins do not function in TGN vesicle formation. However, myosin VI and optineurin colocalize with secretory vesicles at the plasma membrane. Furthermore, live-cell total internal reflection fluorescence microscopy demonstrates that myosin VI or optineurin depletion reduces the total number of vesicle fusion events at the plasma membrane and increases both the proportion of incomplete fusion events and the number of docked vesicles in this region. These results suggest a novel role for myosin VI and optineurin in regulation of fusion pores formed between secretory vesicles and the plasma membrane during the final stages of secretion. C1 [Bond, Lisa M.; Peden, Andrew A.; Buss, Folma] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England. [Bond, Lisa M.; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Kendrick-Jones, John] MRC Lab Mol Biol, Cambridge CB2 OQH, England. RP Buss, F (reprint author), Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England. EM fb1@mole.bio.cam.ac.uk FU Wellcome Trust; Winston Churchill Foundation of the United States; NIH; Medical Research Council FX We thank G. Patterson (Lippincott-Schwartz Lab, National Institute of Child Health and Human Development) for the GalT-mRFP plasmid, M. Gratian and M. Bowen (Cambridge Institute for Medical Research [CIMR] Microscopy) for assistance with imaging and analysis, D. Gordon (Peden Lab, CIMR) for assistance with the assay cell line, and both C. Combs (National Institutes of Health [NIH] Light Microscopy Core Facility) and T. Sakamoto (Wayne State University) for assistance with the vesicle tracking software. This work was funded by the Wellcome Trust (F.B.), a scholarship from the Winston Churchill Foundation of the United States (L.B.), and an NIH-Oxford-Cambridge Ph.D. studentship (L.B.) and was supported by the Medical Research Council (J.K-J.). The CIMR is in receipt of a strategic award from the Wellcome Trust. NR 65 TC 40 Z9 43 U1 1 U2 5 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 1 PY 2011 VL 22 IS 1 BP 54 EP 65 DI 10.1091/mbc.E10-06-0553 PG 12 WC Cell Biology SC Cell Biology GA 703FF UT WOS:000285962300006 PM 21148290 ER PT J AU Arias, I AF Arias, I. TI The role of graduate education in bridging the gap between basic sciences and human health SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Arias, I.] NICHD Cell Biol & Metab, 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 2011 VL 22 MA 27 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500028 ER PT J AU Banerjee, A Nossal, R AF Banerjee, A. Nossal, R. TI Dynamics of Clathrin Coated Pits. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Banerjee, A.] NIH, Bethesda, MD 20892 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 2011 VL 22 MA 1027 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502144 ER PT J AU Banerjee, A Nossal, R AF Banerjee, A. Nossal, R. TI Kinetic Aspects of Clathrin Coated Pit Formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Banerjee, A.; Nossal, R.] NIH, Bethesda, MD 20892 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 2011 VL 22 MA 88 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500089 ER PT J AU Billington, N Wang, A Nagy, A Sellers, JR Adelstein, RS AF Billington, N. Wang, A. Nagy, A. Sellers, J. R. Adelstein, R. S. TI Defining the Properties of Nonmuscle Myosin IIs Using Full Length Proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Billington, N.; Nagy, A.; Sellers, J. R.] NHLBI, LMP, Bethesda, MD 20892 USA. [Wang, A.; Adelstein, R. S.] NHLBI, LMC, 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 2011 VL 22 MA 294 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500293 ER PT J AU Bonnemaison, M Lin, Y Bonifacino, J Mains, R Eipper, B AF Bonnemaison, M. Lin, Y. Bonifacino, J. Mains, R. Eipper, B. TI Interaction of PAM with mu 1A subunit of AP-1 affects trafficking in AtT-20 cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Bonnemaison, M.; Eipper, B.] U Conn Hlth Ctr, Mol Microbial & Struct Biol Dept, Farmington, CT USA. [Lin, Y.; Bonifacino, J.] NICHD, Cell Biol & Metab Program, Farmington, CT USA. [Mains, R.] U Conn Hlth Ctr, Dept Neurosci, Farmington, CT 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 2011 VL 22 MA 1620 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503205 ER PT J AU Boulanger, CA Bruno, RD Rosu-Myles, M Smith, GH AF Boulanger, C. A. Bruno, R. D. Rosu-Myles, M. Smith, G. H. TI The Mouse Mammary Microenvironment Redirects Cells from Mesoderm-derived Bone Marrow Cells to a Mammary Epithelial Progenitor Cell Fate. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Boulanger, C. A.; Bruno, R. D.; Smith, G. H.] NCI, 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 2011 VL 22 MA 1327 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502441 ER PT J AU Bui, M Dimitriadis, E Dalal, Y AF Bui, M. Dimitriadis, E. Dalal, Y. TI CENP-A Nucleosome Structure Transits Between Tetramers and Octamers Throughout the Cell Cycle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Bui, M.; Dimitriadis, E.; Dalal, Y.] 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 2011 VL 22 MA 1110 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502225 ER PT J AU Calliari, A Puppo, A Mercer, J Munroe, D Sotelo, J Sotelo-Silveira, JR AF Calliari, A. Puppo, A. Mercer, J. Munroe, D. Sotelo, J. Sotelo-Silveira, J. R. TI A subset of axonally transported RNAs associates with Myosin Va in ribonucleoprotein complexes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Calliari, A.; Sotelo, J.] Inst Inv Biol Clemente Estable, DPAN, Montevideo, Uruguay. [Puppo, A.] Telethon Inst Genet & Med, Naples, Italy. [Mercer, J.] McLaughlin Res Inst, Great Falls, MT USA. [Munroe, D.] NCI, SAIC, NIH, Frederick, MD 21701 USA. [Sotelo-Silveira, J. R.] UdelaR, Sch Sci, Montevideo, Uruguay. 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 2011 VL 22 MA 1711 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503293 ER PT J AU Case, L Waterman, C AF Case, L. Waterman, C. TI Ventral F-actin waves are coupled to a novel integrin-mediated adhesion complex SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Case, L.; Waterman, C.] NHLBI, NIH, Bethesdsa, 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 2011 VL 22 MA 1579 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503164 ER PT J AU Chavez, KJ Stone, B Lipkowitz, S AF Chavez, K. J. Stone, B. Lipkowitz, S. TI Growth Inhibitory Effects of Death Receptor 5 Agonist, Drozitumab alone and in Combination with the Novel Spirocyclic Lignan Ramonanin A. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Chavez, K. J.; Stone, B.; Lipkowitz, S.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 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 2011 VL 22 MA 2181 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505504213 ER PT J AU Chen, J Liu, J AF Chen, J. Liu, J. TI Spatial Localization Regulated By the Microtubule Network. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Chen, J.; Liu, J.] 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 2011 VL 22 MA 1425 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503013 ER PT J AU David, A Dolan, B Hickman, H Seedhom, M Bennink, J Yewdell, J AF David, A. Dolan, B. Hickman, H. Seedhom, M. Bennink, J. Yewdell, J. TI "Journey to the Center of Translation: In Situ Visualization and Characterization of Compartmentalized Protein Synthesis in Cells and Tissues" SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [David, A.; Dolan, B.; Hickman, H.; Seedhom, M.; Bennink, J.; Yewdell, J.] NIAID, LVD, NIH, Bethesda, MD 20892 USA. 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 2011 VL 22 MA 755 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501308 ER PT J AU Doyle, AD Kutys, ML Conti, MA Matsumoto, K Adelstein, RS Yamada, KM AF Doyle, A. D. Kutys, M. L. Conti, M. A. Matsumoto, K. Adelstein, R. S. Yamada, K. M. TI Microenvironmental control of cell migration: Myosin IIA is required for efficient migration in fibrillar environments through control of cell adhesion dynamics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Doyle, A. D.; Kutys, M. L.; Matsumoto, K.; Yamada, K. M.] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Conti, M. A.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD USA. 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 2011 VL 22 MA 354 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500353 ER PT J AU Duhagon, MA Hurt, E Sotelo-Silveira, JR Fort, R Zhang, X Farrar, WL AF Duhagon, M. A. Hurt, E. Sotelo-Silveira, J. R. Fort, R. Zhang, X. Farrar, W. L. TI Mir-301b modulates proliferation, invasion and cancer stem cell differentiation through the inhibition of multiple RNA targets. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Duhagon, M. A.; Fort, R.] UDELAR Fac Ciencias, Lab Interacc Mol, Montevideo, Uruguay. [Hurt, E.] NCI Frederick, NCI Frederick Oncol, Frederick, Uruguay. [Duhagon, M. A.; Fort, R.] UDELAR Fac Med, Montevideo, Uruguay. [Sotelo-Silveira, J. R.] IIBCE, Montevideo, Uruguay. [Zhang, X.; Farrar, W. L.] NCI Frederick, LCP Canc Stem Cell Sect, Frederick, MD 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 2011 VL 22 MA 707 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501260 ER PT J AU Dutta, D Donaldson, JG AF Dutta, D. Donaldson, J. G. TI Cross-talk between Clathrin-dependent and Clathrin-independent Endocytic Entry and Trafficking Pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Dutta, D.; Donaldson, J. G.] NHLBI, Cell Biol 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 2011 VL 22 MA 444 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500442 ER PT J AU Fontainhas, AM Heymann, JA Fang, S Hinshaw, JE AF Fontainhas, A. M. Heymann, J. A. Fang, S. Hinshaw, J. E. TI Molecular architecture of OPA1, the dynamin-related GTPase involved in mitochondrial fusion. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Fontainhas, A. M.; Heymann, J. A.; Fang, S.; Hinshaw, J. E.] NIDDK, LCBB, NIH, Bethesda, MD USA. NR 1 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 2011 VL 22 MA 2001 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505504032 ER PT J AU Gao, JL Tuo, J Schneider, EH Despres, D Lizak, M Maminishkis, A Chan, CC Murphy, PM AF Gao, J-L. Tuo, J. Schneider, E. H. Despres, D. Lizak, M. Maminishkis, A. Chan, C. C. Murphy, P. M. TI The N-formylpeptide Receptor FPR1 Is Functionally Expressed in Lens Epithelial Cells and is Critical for Lens Maintenance in Mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Gao, J-L.; Tuo, J.; Schneider, E. H.; Despres, D.; Lizak, M.; Maminishkis, A.; Chan, C. C.; Murphy, P. M.] 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 2011 VL 22 MA 2054 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505504086 ER PT J AU Grati, M Kachar, B AF Grati, M. Kachar, B. TI Myosin VIIa and sans localization at inner ear hair cell stereocilia upper tip-link density (UTLD) implicates these Usher syndrome proteins in mechanotransduction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Grati, M.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. 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 2011 VL 22 MA 309 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500308 ER PT J AU Hasegawa, K Ryu, S Kalab, P AF Hasegawa, K. Ryu, S. Kalab, P. TI Attenuation of mitotic RanGTP gradient in normal somatic cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Hasegawa, K.; Ryu, S.; Kalab, P.] NCI, LCMB, 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 2011 VL 22 MA 2272 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505504301 ER PT J AU Jolly, C Winfree, S Steele-Mortimer, O AF Jolly, C. Winfree, S. Steele-Mortimer, O. TI The Giant Phosphoprotein AHNAK is Required for Salmonella Invasion of Non-Phagocytic Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Jolly, C.; Winfree, S.; Steele-Mortimer, O.] NIH NIAID RML, LICP, Hamilton, MT 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 2011 VL 22 MA 1201 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502316 ER PT J AU Karabasheva, D Cole, NB Donaldson, JG AF Karabasheva, D. Cole, N. B. Donaldson, J. G. TI A Model System to Study Turnover of Plasma Membrane Proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Karabasheva, D.; Cole, N. B.; Donaldson, J. G.] NLHBI, 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 2011 VL 22 MA 450 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501003 ER PT J AU Knodler, L Steele-Mortimer, O AF Knodler, L. Steele-Mortimer, O. TI Salmonella enterica and epithelial cells: life in a vacuole or the cytosol? SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Knodler, L.; Steele-Mortimer, O.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 2011 VL 22 MA 179 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500179 ER PT J AU Krispin, S Yu, J Mulligan, T Davis, A Castranova, D Weinstein, BM AF Krispin, S. Yu, J. Mulligan, T. Davis, A. Castranova, D. Weinstein, B. M. TI F3 ENU genetic screen - a quest for endothelial cells directional movement cues. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Krispin, S.] NICHHD, Program Genom Differentiat, 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 2011 VL 22 MA 2317 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505504346 ER PT J AU Lee, S Tipirneni, A Yang, S Blackstone, C AF Lee, S. Tipirneni, A. Yang, S. Blackstone, C. TI The novel MIT-domain-containing protein MITD1 interacts with ESCRT-III proteins and functions in cytokinesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Lee, S.; Tipirneni, A.; Yang, S.; Blackstone, C.] NINDS, 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 2011 VL 22 MA 532 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501085 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, J. TI Navigating the cellular landscape with new optical probes, imaging strategies and technical innovations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Lippincott-Schwartz, J.] NICHD, 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 2011 VL 22 MA 51 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500052 ER PT J AU Malide, D Metais, JY Dunbar, CE AF Malide, D. Metais, J-Y. Dunbar, C. E. TI Multispectral cell tracking and dynamic analysis in intact tissues using confocal and multiphoton microscopy of five fluorescent proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Malide, D.] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. [Metais, J-Y.; Dunbar, C. E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 2011 VL 22 MA 1326 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502440 ER PT J AU Manor, U Disanza, A Grati, M Andrade, L Lin, H Di Fiore, P Scita, G Kachar, B AF Manor, U. Disanza, A. Grati, M. Andrade, L. Lin, H. Di Fiore, P. Scita, G. Kachar, B. TI Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Manor, U.; Grati, M.; Andrade, L.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA. [Disanza, A.; Di Fiore, P.; Scita, G.] Fdn IFOM, FIRC Inst Mol Oncol, Milan, Italy. [Lin, H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. FU Associazione Italiana per la Ricerca sul Cancro 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 2011 VL 22 MA 1403 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502516 ER PT J AU Manor, U Disanza, A Grati, M Andrade, L Lin, H Di Fiore, P Scita, G Kachar, B AF Manor, U. Disanza, A. Grati, M. Andrade, L. Lin, H. Di Fiore, P. Scita, G. Kachar, B. TI Regulation of stereocilia length by myosin XVa and whirlin depends on the actin-regulatory protein Eps8 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Manor, U.; Grati, M.; Andrade, L.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, Bethesda, MD USA. [Disanza, A.; Di Fiore, P.; Scita, G.] Fdn IFOM, FIRC Inst Mol Oncol, Milan, Italy. [Lin, H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. FU Associazione Italiana per la Ricerca sul Cancro 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 2011 VL 22 MA 14 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500015 ER PT J AU Martina, J Puertollano, R AF Martina, J. Puertollano, R. TI Mucolipin-1 induces fusion of lysosomes with the plasma membrane. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Martina, J.; Puertollano, R.] 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 2011 VL 22 MA 1636 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503220 ER PT J AU Masedunskas, A Sramkova, M Parente, L Sales, KU Amornphimoltham, P Bugge, T Weigert, R AF Masedunskas, A. Sramkova, M. Parente, L. Sales, K. Uzzun Amornphimoltham, P. Bugge, T. Weigert, R. TI Role for the acto-myosin complex in regulated exocytosis revealed by intravital microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Masedunskas, A.; Sramkova, M.; Parente, L.; Sales, K. Uzzun; Amornphimoltham, P.; Bugge, T.; Weigert, R.] NIDCR, OPCB, 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 2011 VL 22 MA 411 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500409 ER PT J AU Michelotti, JM Opishinski, D Herman, K Deiuliis, N Jett, C AF Michelotti, J. M. Opishinski, D. Herman, K. Deiuliis, N. Jett, C. TI Use of Fully Automated Cell Culture and Imaging Systems to Increase the Capacity and Consistency of Downstream Virology Assays. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Michelotti, J. M.; Opishinski, D.; Herman, K.; Deiuliis, N.; Jett, C.] NIAID, IRF, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 2011 VL 22 MA 1947 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503527 ER PT J AU Mital, J Lutter, E Hackstadt, T AF Mital, J. Lutter, E. Hackstadt, T. TI Defining the roles of inclusion membrane microdomain proteins in chlamydial pathogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Mital, J.; Lutter, E.; Hackstadt, T.] Rocky Mt Labs NIH, Hamilton, MT 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 2011 VL 22 MA 2199 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505504231 ER PT J AU Myers, KA Waterman, CM AF Myers, K. A. Waterman, C. M. TI MCAK activity controls microtubule dynamics and directed cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Myers, K. A.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 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 2011 VL 22 MA 843 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501395 ER PT J AU Myers, KA Waterman, CM AF Myers, K. A. Waterman, C. M. TI MCAK activity controls microtubule dynamics and directed cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Myers, K. A.; Waterman, C. M.] NHLBI, Cell Biol & Physiol Ctr, 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 2011 VL 22 MA 96 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500097 ER PT J AU Oddoux, S Tate, V Nandkeolyar, S Liu, W Zaal, KJ Ralston, E AF Oddoux, S. Tate, V. Nandkeolyar, S. Liu, W. Zaal, K. J. Ralston, E. TI Microtubule Dynamics and Nucleation in Live Muscle Fibers. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Oddoux, S.; Tate, V.; Nandkeolyar, S.; Liu, W.; Zaal, K. J.; Ralston, E.] NIAMS, Light Imaging Sect, Off Sci & Technol, NIH, Bethesda, MD USA. RI Liu, Wenhua/B-8044-2010 OI Liu, Wenhua/0000-0002-1199-435X NR 0 TC 0 Z9 0 U1 0 U2 5 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 2011 VL 22 MA 254 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500253 ER PT J AU Olszewski, MB Chandris, P Eisenberg, E Greene, LE AF Olszewski, M. B. Chandris, P. Eisenberg, E. Greene, L. E. TI Inhibition of Clathrin Dependent Endocytosis Results in Senescence-like phenotype and Plk4-mediated Centrosome Overduplication. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Olszewski, M. B.; Chandris, P.; Eisenberg, E.; Greene, L. E.] NHLBI, NIH, CBPC, LCB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 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 2011 VL 22 MA 895 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502013 ER PT J AU Porat-Shliom, N Masedunskas, A Weigert, R AF Porat-Shliom, N. Masedunskas, A. Weigert, R. TI Fast oscillations of NAD(P)H in the salivary glands epithelium of live rats imaged by intravital two-photon microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Porat-Shliom, N.; Masedunskas, A.; Weigert, R.] NIDCR, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, 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 2011 VL 22 MA 1684 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503266 ER PT J AU Renz, M Daniels, B Arias, I Lippincott-Schwartz, J AF Renz, M. Daniels, B. Arias, I. Lippincott-Schwartz, J. TI Plasticity of the Asialoglycoprotein Receptor deciphered by ensemble FRET and Single-Molecule Counting PALM SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Renz, M.; Daniels, B.; Arias, I.; Lippincott-Schwartz, J.] NICHHD, NIH, Bethesda, MD 20892 USA. NR 2 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 2011 VL 22 MA 1945 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505503525 ER PT J AU Shu, S Liu, X Kriebel, P Daniels, M Korn, E AF Shu, S. Liu, X. Kriebel, P. Daniels, M. Korn, E. TI Actin Crosslinking Proteins, Cortexillin I and II, are Required for cAMP-signaling During Dictyostelium Chemotaxis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Shu, S.; Liu, X.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Kriebel, P.] NCI, NIH, Bethesda, MD 20892 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 2011 VL 22 MA 327 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500326 ER PT J AU Smyth, JT Beg, AM Putney, JW Rusan, NM AF Smyth, J. T. Beg, A. M. Putney, J. W. Rusan, N. M. TI Proper ER morphology and partitioning during mitosis require phosphorylation-driven dissociation of STIM1 from EB1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Smyth, J. T.; Beg, A. M.; Rusan, N. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Putney, J. W.] NIEHS, NIH, Res Triangle Pk, NC 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 2011 VL 22 MA 540 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501093 ER PT J AU Turbyville, T Chen, D Hott, A Donkor, J Kirkwood, J Brafman, A Beutler, J Reilly, K Lockett, S AF Turbyville, T. Chen, D. Hott, A. Donkor, J. Kirkwood, J. Brafman, A. Beutler, J. Reilly, K. Lockett, S. TI A Natural Product, Schweinfurthin A, Inhibits the Growth Kinetics of Malignant Peripheral Sheath Tumor Cells with Quantitative Effects on Actin Cytoskeleton Morphology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Turbyville, T.; Chen, D.; Hott, A.; Donkor, J.; Kirkwood, J.; Brafman, A.; Lockett, S.] SAIC Frederick Inc, Opt Microscopy & Image Anal Lab, Frederick, MD USA. [Beutler, J.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Lockett, S.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 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 2011 VL 22 MA 1376 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502489 ER PT J AU Varticovski, L Thompson, B Grontved, L Stavreva, D Hager, G AF Varticovski, L. Thompson, B. Grontved, L. Stavreva, D. Hager, G. TI Characterization of Transcriptional Regulation in iPS Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) DE chromatin organization; differentiation; DNAse I hypersensitive sites; microarray; osteoblast; transcriptional regulation C1 [Varticovski, L.; Thompson, B.; Grontved, L.; Stavreva, D.; Hager, G.] NCI, LRBGE, 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 2011 VL 22 MA 1092 PG 2 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505502207 ER PT J AU Wang, X He, H Zheng, W Chen, G Yan, J AF Wang, X. He, H. Zheng, W. Chen, G. Yan, J. TI Characterization of blastema formation and pattern reformation during lower jaw regeneration in zebrafish SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) DE zebrafish; jaw; regeneration; blastema; cellular memory C1 [Wang, X.; He, H.; Zheng, W.; Yan, J.] Shanghai Ocean Univ, Coll Fishiers & Life Sci, Shanghai, Peoples R China. [Chen, G.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 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 2011 VL 22 MA 151 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500152 ER PT J AU Wu, Z Plotnikov, S Waterman, CM Liu, J AF Wu, Z. Plotnikov, S. Waterman, C. M. Liu, J. TI A mechanochemistry model of focal adhesion dynamics in cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Wu, Z.; Plotnikov, S.; Waterman, C. M.; Liu, J.] NHLBI, NIH, Bethesda, MD 20892 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 2011 VL 22 MA 343 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505500342 ER PT J AU Zhang, ZR Hegde, RS AF Zhang, Z-R. Hegde, R. S. TI Mechanistic basis of host-cell remodeling by the HIV-1 protein Vpu. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Cell-Biology (ASCB) CY DEC 03-07, 2011 CL Denver, CO SP Amer Soc Cell Biol (ASCB) C1 [Zhang, Z-R.; Hegde, R. S.] 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 2011 VL 22 MA 634 PG 1 WC Cell Biology SC Cell Biology GA 961YM UT WOS:000305505501187 ER PT J AU Cohen-Gihon, I Fong, JH Sharan, R Nussinov, R Przytycka, TM Panchenko, AR AF Cohen-Gihon, Inbar Fong, Jessica H. Sharan, Roded Nussinov, Ruth Przytycka, Teresa M. Panchenko, Anna R. TI Evolution of domain promiscuity in eukaryotic genomes-a perspective from the inferred ancestral domain architectures SO MOLECULAR BIOSYSTEMS LA English DT Article ID MULTIDOMAIN PROTEINS; ORGANIZATION; REARRANGEMENTS; DUPLICATION; COMPLEXITY; FAMILIES; DATABASE; TOOL AB Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. C1 [Fong, Jessica H.; Przytycka, Teresa M.; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Cohen-Gihon, Inbar; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. [Sharan, Roded] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Sharan, Roded; Nussinov, Ruth] NCI, Ctr Canc Res, Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM przytyck@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; National Library of Medicine at National Institutes of Health/DHHS; Israel Science Foundation [385/06]; Tel Aviv University FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported ( in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the National Library of Medicine at National Institutes of Health/DHHS. RS was supported by a research grant from the Israel Science Foundation (grant no. 385/06). ICG is a fellow of the Edmond J. Safra Bioinformatics Program and of the Ela Kodesz Research and Scholarship Fund at Tel Aviv University. NR 46 TC 8 Z9 8 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2011 VL 7 IS 3 BP 784 EP 792 DI 10.1039/c0mb00182a PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 721PM UT WOS:000287367100022 PM 21127809 ER PT J AU Liu, G Swierczewska, M Niu, G Zhang, XM Chen, XY AF Liu, Gang Swierczewska, Magdalena Niu, Gang Zhang, Xiaoming Chen, Xiaoyuan TI Molecular imaging of cell-based cancer immunotherapy SO MOLECULAR BIOSYSTEMS LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE-EXPRESSION; SUPERPARAMAGNETIC IRON-OXIDE; NEPHROGENIC SYSTEMIC FIBROSIS; SODIUM-IODIDE SYMPORTER; TYPE-1 THYMIDINE KINASE; MESENCHYMAL STEM-CELLS; GROWTH-FACTOR RECEPTOR; IN-VIVO VISUALIZATION; DENDRITIC CELLS AB Cell-based cancer immunotherapy represents a new and powerful weapon in the arsenal of anticancer treatments. Non-invasive monitoring of the disposition, migration and destination of therapeutic cells will facilitate the development of cell based therapy. The therapeutic cells can be modified intrinsically by a reporter gene or labeled extrinsically by introducing imaging probes into the cells or on the cell surface before transplant. Various advanced non-invasive molecular imaging techniques are playing important roles in optimizing cellular therapy by tracking cells and monitoring the therapeutic effects of transplanted cells in vivo. This review will summarize the application of multiple molecular imaging modalities in cell-based cancer immunotherapy. C1 [Liu, Gang; Swierczewska, Magdalena; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Liu, Gang; Zhang, Xiaoming] N Sichuan Med Coll, Affiliated Hosp, Sichuan Key Lab Med Imaging, Nanchong 637007, Peoples R China. [Liu, Gang] N Sichuan Med Coll, Inst Mat Med, Nanchong 637007, Sichuan, Peoples R China. [Liu, Gang] N Sichuan Med Coll, Dept Pharmacol, Nanchong 637007, Sichuan, Peoples R China. [Niu, Gang] Radiol & Imaging Sci Clin Ctr, Imaging Sci Training Program, Bethesda, MD 20892 USA. RP Niu, G (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,9 Mem Dr,9-1W111,1C22, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU Sichuan Province, China [09ZA036KFJJ0905]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009]; Radiology and Imaging Sciences Department of NIH Clinical Center; IRP/NIBIB, NIH FX This work was partially supported by projects (No. 09ZA036&KFJJ0905) of Sichuan Province, China, the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), and the International Cooperative Program of National Science Foundation of China (NSFC) (81028009). G.N. acknowledges an Imaging Sciences Training Fellowship jointly funded by the Radiology and Imaging Sciences Department of NIH Clinical Center and by the IRP/NIBIB, NIH. NR 130 TC 16 Z9 16 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2011 VL 7 IS 4 BP 993 EP 1003 DI 10.1039/c0mb00198h PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 734JB UT WOS:000288329300003 PM 21308113 ER PT J AU Burbelo, PD Bren, KE Ching, KH Gogineni, ES Kottilil, S Cohen, JI Kovacs, JA Iadarola, MJ AF Burbelo, Peter D. Bren, Kathleen E. Ching, Kathryn H. Gogineni, Emile S. Kottilil, Shyam Cohen, Jeffrey I. Kovacs, Joseph A. Iadarola, Michael J. TI LIPS arrays for simultaneous detection of antibodies against partial and whole proteomes of HCV, HIV and EBV SO MOLECULAR BIOSYSTEMS LA English DT Article ID HUMORAL IMMUNE-RESPONSE; PROTEIN MICROARRAYS; INFECTIOUS AGENTS; PROFILES; DISEASE; VACCINE AB For many infectious agents, the detection of antibodies is critical for diagnosing, monitoring and understanding vaccine responses. To facilitate the highly quantitative and simultaneous analysis of antibodies against multiple proteins from infectious agents, we have developed Luciferase Immunoprecipitation Systems (LIPS) arrays. By configuring microtiter plates with multiple antigens and testing control and infected serum samples at one time in solution, LIPS arrays provided highly reproducible antibody titers to panels of antigens with a wide dynamic range of detection. While all serum samples showed similar positive and negative immunoreactivity with internal control antigens derived from Influenza and Renilla luciferase-alone protein, respectively, antibody titers to many HCV and HIV antigens were generally 10 to over 400-fold higher in the infected versus uninfected samples. Additional screening of 18 proteins from the EBV proteome with serum samples from healthy EBV-infected individuals showed statistically significant antibody titers to 50% of the proteins tested. Antibody titers for the different EBV antigens in the healthy EBV-infected individuals were markedly heterogeneous highlighting the complexity of host humoral responses. These results suggest that LIPS arrays offer a highly discriminating platform for simultaneously profiling a wide spectrum of antibodies associated with many infectious agents. C1 [Burbelo, Peter D.; Bren, Kathleen E.; Ching, Kathryn H.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Gogineni, Emile S.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Cohen, Jeffrey I.] NIAID, Med Virol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Bldg 49,Room 1C36,49 Convent Dr, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases; Clinical Center, NIH; NIH Clinical Research Center FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, the National Institute of Allergy and Infectious Diseases, the Clinical Center, NIH, and in part, by a Bench to Bedside award from the NIH Clinical Research Center. NR 25 TC 16 Z9 17 U1 0 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2011 VL 7 IS 5 BP 1453 EP 1462 DI 10.1039/c0mb00342e PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 748CI UT WOS:000289367200009 PM 21336381 ER PT J AU Hunt, RC Geetha, S Allen, CE Hershko, K Fathke, R Kong, PL Plum, E Struble, EB Soejima, K Friedman, S Garfield, S Balaji, S Kimchi-Sarfaty, C AF Hunt, Ryan C. Geetha, S. Allen, Courtni E. Hershko, Klilah Fathke, Robert Kong, Philip L. Plum, Elizabeth Struble, Evi Budo Soejima, Kenji Friedman, Scott Garfield, Susan Balaji, S. Kimchi-Sarfaty, Chava TI Detection of a secreted metalloprotease within the nuclei of liver cells SO MOLECULAR BIOSYSTEMS LA English DT Article ID VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; LOCALIZATION SIGNALS; PROSTATE-CANCER; STELLATE CELLS; CUB DOMAINS; ADAMTS13; PROTEIN; TRANSLOCATION; IDENTIFICATION AB ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus. C1 [Garfield, Susan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hunt, Ryan C.; Geetha, S.; Allen, Courtni E.; Hershko, Klilah; Fathke, Robert; Kong, Philip L.; Plum, Elizabeth; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol, Bethesda, MD 20892 USA. [Struble, Evi Budo] US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol, Bethesda, MD 20892 USA. [Soejima, Kenji] Chemoserotherapeut Res Inst, Res Dept 1, Kumamoto, Japan. [Friedman, Scott] Mt Sinai Sch Med, Div Liver Dis, New York, NY 10029 USA. [Balaji, S.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Garfield, S (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM Susan.Garfield@nih.hhs.gov; Balaji_Santhanam@DFCI.HARVARD.EDU; Chava.kimchi-sarfaty@fda.hhs.gov FU Intramural NIH HHS [Z01 BC010858-01] NR 34 TC 4 Z9 4 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2011 VL 7 IS 6 BP 2012 EP 2018 DI 10.1039/c0mb00303d PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763PR UT WOS:000290572700023 PM 21479334 ER PT J AU Burroughs, AM Iyer, LM Aravind, L AF Burroughs, A. Maxwell Iyer, Lakshminarayan M. Aravind, L. TI Functional diversification of the RING finger and other binuclear treble clef domains in prokaryotes and the early evolution of the ubiquitin system SO MOLECULAR BIOSYSTEMS LA English DT Article ID ZINC-BINDING DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; MYND-DOMAIN; SULFUR TRANSFER; FYVE DOMAIN; DNA-BINDING; PHD FINGER; MYCOBACTERIUM-TUBERCULOSIS; COMPARATIVE GENOMICS AB Recent studies point to a diverse assemblage of prokaryotic cognates of the eukaryotic ubiquitin (Ub) system. These systems span an entire spectrum, ranging from those catalyzing cofactor and amino acid biosynthesis, with only adenylating E1-like enzymes and ubiquitin-like proteins (Ubls), to those that are closer to eukaryotic systems by virtue of possessing E2 enzymes. Until recently E3 enzymes were unknown in such prokaryotic systems. Using contextual information from comparative genomics, we uncover a diverse group of RING finger E3s in prokaryotes that are likely to function with E1s, E2s, JAB domain peptidases and Ubls. These E1s, E2s and RING fingers suggest that features hitherto believed to be unique to eukaryotic versions of these proteins emerged progressively in such prokaryotic systems. These include the specific configuration of residues associated with oxyanion-hole formation in E2s and the C-terminal UFD in the E1 enzyme, which presents the E2 to its active site. Our study suggests for the first time that YukD-like Ubls might be conjugated by some of these systems in a manner similar to eukaryotic Ubls. We also show that prokaryotic RING fingers possess considerable functional diversity and that not all of them are involved in Ub-related functions. In eukaryotes, other than RING fingers, a number of distinct binuclear (chelating two Zn atoms) and mononuclear (chelating one zinc atom) treble clef domains are involved in Ub-related functions. Through detailed structural analysis we delineated the higher order relationships and interaction modes of binuclear treble clef domains. This indicated that the FYVE domain acquired the binuclear state independently of the other binuclear forms and that different treble clef domains have convergently acquired Ub-related functions independently of the RING finger. Among these, we uncover evidence for notable prokaryotic radiations of the ZF-UBP, B-box, AN1 and LIM clades of treble clef domains and present contextual evidence to support their role in functions unrelated to the Ub-system in prokaryotes. In particular, we show that bacterial ZF-UBP domains are part of a novel cyclic nucleotide-dependent redox signaling system, whereas prokaryotic B-box, AN1 and LIM domains have related functions as partners of diverse membrane-associated peptidases in processing proteins. This information, in conjunction with structural analysis, suggests that these treble clef domains might have been independently recruited to the eukaryotic Ub-system due to an ancient conserved mode of interaction with peptides. C1 [Iyer, Lakshminarayan M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Burroughs, A. Maxwell] RIKEN Yokohama Inst, OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov FU National Library of Medicine at the National Institutes of Health, USA FX Work by LMI and LA is supported by the intramural funds of the National Library of Medicine at the National Institutes of Health, USA. Supplementary material can be found at: ftp://ftp.ncbi.nih.gov/pub/aravind/PROKRING/prok_rings_supplementary.htm l NR 116 TC 34 Z9 34 U1 2 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2011 VL 7 IS 7 BP 2261 EP 2277 DI 10.1039/c1mb05061c PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 776TC UT WOS:000291559900019 PM 21547297 ER PT J AU Chen, G Ghosh, P Longo, DL AF Chen, Gang Ghosh, Paritosh Longo, Dan L. TI Distinctive Mechanism for Sustained TGF-beta Signaling and Growth Inhibition: MEK1 Activation-Dependent Stabilization of Type II TGF-beta Receptors SO MOLECULAR CANCER RESEARCH LA English DT Article ID DOMAIN PROTEIN; CELL-LINES; EXPRESSION; SMAD7; CANCER; PATHWAY; GENE; LYMPHOMA; IDENTIFICATION; TRANSDUCTION AB There are multiple mechanisms by which cells evade TGF-beta-mediated growth inhibitory effects. In this report, we describe a novel mechanism by which cells become resistant to TGF-beta-mediated growth suppression. Although having all the components of the TGF-beta signaling pathway, different cell lines, RL, HaCaT, and BJAB, have different sensitivities toward TGF-beta-induced growth suppression. The TGF-beta resistance of RL, a B-cell lymphoma cell line, was due to ligand-induced downregulation of TGF-beta receptor II (T beta RII) and only transient TGF-beta induced nuclear translocation of Smad2 and Smad3. With low-dose phorbol 12-myristate 13-acetate (PMA) or anti-IgM treatment, TGF-beta sensitivity was restored by stabilizing T beta RII expression and sustaining TGF-beta signaling. The MEK inhibitor, U0126, blocked both PMA- and anti-IgM-induced upregulation of T beta RII. In HaCaT and BJAB, two TGF-beta-sensitive cell lines, which had higher basal levels of phospho-MEK and T beta RII compared with RL, U0126 induced downregulation of T beta RII and blocked subsequent TGF-beta signaling. Similar results were also obtained with normal B cells, where MEK1 inhibitor downregulated T beta RII and subsequent TGF-beta signaling. Constitutively active MEK1, but not constitutively active ERK2, induced upregulation of T beta RII. Furthermore, T beta RII physically interacted with the constitutively active MEK1, but not with wild-type MEK1, indicating involvement of active MEK1 in stabilizing T beta RII. Collectively, our data suggest a novel mechanism for MEK1 in regulating the sensitivity to TGF-beta signaling by stabilizing T beta RII. Mol Cancer Res; 9(1); 78-89. (C) 2010 AACR. C1 [Ghosh, Paritosh] NIA, Lymphocyte Cell Biol Sect, Immunol Lab,NIH, Biomed Res Ctr,Lymphocyte Cell Biol Unit,Intramur, Baltimore, MD 21224 USA. RP Ghosh, P (reprint author), NIA, Lymphocyte Cell Biol Sect, Immunol Lab,NIH, Biomed Res Ctr,Lymphocyte Cell Biol Unit,Intramur, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM ghoshp@grc.nia.nih.gov FU NIH, National Institute on Aging FX This research was supported (in part) by the Intramural Research Program of the NIH, National Institute on Aging. NR 45 TC 5 Z9 6 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JAN PY 2011 VL 9 IS 1 BP 78 EP 89 DI 10.1158/1541-7786.MCR-10-0216 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 706LU UT WOS:000286220700007 PM 21131601 ER PT J AU Khositseth, S Pisitkun, T Slentz, DH Wang, GH Hoffert, JD Knepper, MA Yu, MJ AF Khositseth, Sookkasem Pisitkun, Trairak Slentz, Dane H. Wang, Guanghui Hoffert, Jason D. Knepper, Mark A. Yu, Ming-Jiun TI Quantitative Protein and mRNA Profiling Shows Selective Post-Transcriptional Control of Protein Expression by Vasopressin in Kidney Cells SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID MEDULLARY COLLECTING DUCT; PRINCIPAL CELLS; AQUAPORIN-2 TRAFFICKING; STIMULATED INCREASE; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; GENE-EXPRESSION; BRATTLEBORO RAT; MYOSIN-II; LC-MS/MS AB Previous studies in yeast have supported the view that post-transcriptional regulation of protein abundances may be more important than previously believed. Here we ask the question: "In a physiological regulatory process (the response of mammalian kidney cells to the hormone vasopressin), what fraction of the expressed proteome undergoes a change in abundance and what fraction of the regulated proteins have corresponding changes in mRNA levels?" In humans and other mammals, vasopressin fulfills a vital homeostatic role (viz. regulation of renal water excretion) by regulating the water channel aquaporin-2 in collecting duct cells. To address the question posed, we utilized large-scale quantitative protein mass spectrometry (LC-MS/MS) employing stable isotopic labeling in cultured mpkCCD cells ('SILAC') coupled with transcriptomic profiling using oligonucleotide expression arrays (Affymetrix). Preliminary studies analyzing two nominally identical control samples by SILAC LC-MS/MS yielded a relative S. D. of 13% (for ratios), establishing the precision of the SILAC approach in our hands. We quantified nearly 3000 proteins with nontargeted SILAC LCMS/MS, comparing vasopressin-versus vehicle-treated samples. Of these proteins 786 of them were quantified in each of 3 experiments, allowing statistical analysis and 188 of these showed significant vasopressin-induced changes in abundance, including aquaporin-2 (20-fold increase). Among the proteins with statistically significant abundance changes, a large fraction (at least one-third) was found to lack changes in the corresponding mRNA species (despite sufficient statistical power), indicating that post-transcriptional regulation of protein abundance plays an important role in the vasopressin response. Bioinformatic analysis of the regulated proteins (versus all transcripts) shows enrichment of glutathione S-transferase isoforms as well as proteins involved in organization of the actin cytoskeleton. The latter suggests that long-term regulatory processes may contribute to actomyosin-dependent trafficking of the water channel aquaporin-2. The results provide impetus for increased focus on translational regulation and regulation of protein degradation in physiological control in mammalian epithelial cells. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004036, 1-21, 2011. C1 [Khositseth, Sookkasem; Pisitkun, Trairak; Slentz, Dane H.; Wang, Guanghui; Hoffert, Jason D.; Knepper, Mark A.; Yu, Ming-Jiun] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yu, MJ (reprint author), Natl Taiwan Univ, Coll Med, Inst Biochem & Mol Biol, Rm 816,1 Ren Al Rd Section 1, Taipei 100, Taiwan. EM mjyu@ntu.edu.tw OI Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696 FU Division of Intramural Research, NHLBI [ZO1-HL001285]; International Society of Nephrology; Kidney Foundation of Thailand; Faculty of Medicine, Thammasat University, Thailand FX The work was funded by the Division of Intramural Research, NHLBI (project ZO1-HL001285, MAK). SK was supported by the International Society of Nephrology, the Kidney Foundation of Thailand, and the Faculty of Medicine, Thammasat University, Thailand. NR 47 TC 20 Z9 20 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JAN PY 2011 VL 10 IS 1 AR M110.004036 DI 10.1074/mcp.M110.004036 PG 21 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 715XL UT WOS:000286928400020 PM 20940332 ER PT S AU Mollapour, M Neckers, L AF Mollapour, Mehdi Neckers, Len BE Calderwood, SK Prince, TL TI Detecting HSP90 Phosphorylation SO MOLECULAR CHAPERONES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE HSP90; Molecular chaperones; Posttranslational modification; Phosphorylation ID HEAT-SHOCK-PROTEIN; MOLECULAR CHAPERONE; SACCHAROMYCES-CEREVISIAE; ATPASE ACTIVITY; IN-VIVO; CANCER CHAPERONE; RECEPTOR COMPLEX; STRUCTURAL BASIS; BINDING; STI1 AB Heat-shock protein 90 (HSP90) is an essential molecular chaperone in eukaryotes. It is important for chaperoning proteins that are important determinants of multistep carcinogenesis. HSP90's ATPase activity is associated with its chaperone function. Co-chaperones as well as posttranslational modifications (phosphorylation, acetylation, and S-nitrosylation) are important for regulating its ATPase activity. Yeast can be used to express and purify HSP90 and also detect its phosphorylation by pan-phosphoserine or phosphothreonine antibodies. C1 [Mollapour, Mehdi; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Mollapour, M (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 43 TC 3 Z9 3 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-294-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 787 BP 67 EP 74 DI 10.1007/978-1-61779-295-3_5 D2 10.1007/978-1-61779-295-3 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BYL18 UT WOS:000299228600006 PM 21898227 ER PT J AU Smith, AR D'Annunzio, L Smith, AE Sharma, A Hofmann, CM Marshall, NJ Carleton, KL AF Smith, Adam R. D'Annunzio, Lindsay Smith, Abbi E. Sharma, Anit Hofmann, Christopher M. Marshall, N. J. Carleton, Karen L. TI Intraspecific cone opsin expression variation in the cichlids of Lake Malawi SO MOLECULAR ECOLOGY LA English DT Article DE colour vision; cone opsin; expression; light environment; sympatry ID GENE-EXPRESSION; EVOLUTIONARY BIOLOGY; SPECTRAL SENSITIVITY; BLUEFIN KILLIFISH; VICTORIA CICHLIDS; LUCANIA-GOODEI; SENSORY DRIVE; COLOR-VISION; SPECIATION; FISHES AB The expression of cone opsin genes is a primary determinant of the characteristics of colour vision. Interspecific variation in opsin expression is common in African cichlids. It is correlated with foraging among cichlids from Lake Malawi, and with ambient light environment among cichlids from Lake Victoria. In this study, we tested whether gene expression varied within species such that it might be important in contributing to divergence. We hypothesized that light attenuation with depth would be correlated with predictable changes in gene expression in Lake Malawi, and that this variation would tune visual sensitivities to match the ambient light environment. We observed significant differences in cone opsin expression in three different comparisons among populations of the same species. Higher LWS expression was found in shallow versus deep Copadichromis eucinostomus. In Metriaclima zebra, individuals from Zimbawe Rock expressed significantly more SWS2B than those from Thumbi West Island, although these locales have similar ambient light environments. Finally, Tropheops gracilior from deeper water had significantly more variation in expression than their shallow counterparts. These results support that gene expression varies significantly between populations of the same species. Surprisingly, these results could not be explained by predicted visual performance as models predicted that differential expression patterns did not confer sensitivity advantages at different depths. This suggested that expression variation did not confer a local sensitivity advantage. Therefore, our findings were contrary to a primary requirement of the sensory bias hypothesis. As such, other explanations for intraspecific gene expression variation need to be tested. C1 [Smith, Adam R.; D'Annunzio, Lindsay; Smith, Abbi E.; Sharma, Anit; Hofmann, Christopher M.; Carleton, Karen L.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [D'Annunzio, Lindsay] Univ Med & Dent New Jersey, Joint Grad Program Toxicol, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA. [Smith, Abbi E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Marshall, N. J.] Univ Queensland, Sensory Neurobiol Grp, Queensland Brain Inst, St Lucia, Qld, Australia. RP Smith, AR (reprint author), Univ Maryland, Dept Biol, 1210 Biol Psychol Bldg, College Pk, MD 20742 USA. EM adasmi@umd.edu FU National Science Foundation [IOS-0841270]; University of Maryland FX We thank Tom Kocher, James Maluza, Richard Zatha, Kelly O'Quin, Brian Dalton and Jennifer Ser for help with fish collection. Thanks also to all of the members of the cichlid labs at University of Maryland for comments on this manuscript. This work was supported by the National Science Foundation (IOS-0841270) and the University of Maryland. Animals were collected under permits provided by the government of Malawi and retinal samples were collected and processed according to IACUC protocol R-09-73 through the University of Maryland. NR 30 TC 14 Z9 15 U1 1 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1083 EI 1365-294X J9 MOL ECOL JI Mol. Ecol. PD JAN PY 2011 VL 20 IS 2 BP 299 EP 310 DI 10.1111/j.1365-294X.2010.04935.x PG 12 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 703HY UT WOS:000285970200011 PM 21091561 ER PT B AU Calvisi, DF Factor, VM Thorgeirsson, SS AF Calvisi, Diego F. Factor, Valentina M. Thorgeirsson, Snorri S. BE Wang, XW Grisham, JW Thorgeirsson, SS TI Transgenic and Knockout Mouse Models of Liver Cancer SO MOLECULAR GENETICS OF LIVER NEOPLASIA SE Cancer Genetics-Series LA English DT Article; Book Chapter DE Genetically engineered mouse models; Hepatocellular carcinoma; Signal transduction pathways; Oncogenes; Tumor suppressor genes ID GROWTH-FACTOR-ALPHA; HEPATITIS-B-VIRUS; HUMAN HEPATOCELLULAR-CARCINOMA; METHIONINE ADENOSYLTRANSFERASE 1A; COMPARATIVE FUNCTIONAL GENOMICS; BETA-CATENIN MUTATIONS; EXPRESSING C-MYC; NF-KAPPA-B; INDUCED HEPATOCARCINOGENESIS; GENE-EXPRESSION AB Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest tumors worldwide. Only few patients are amenable to surgery due to the late HCC diagnosis, and alternative treatments do not significantly improve the patient prognosis when tumor is unresectable. Thus, the investigation of HCC biology is required to identify new targets for early diagnosis, chemoprevention, and treatment. To study the molecular events leading to liver malignant transformation and tumor progression, a number of mouse models have been generated. Here, we highlight some of the genetically engineered mouse models that have proved to be valuable tools to study the molecular pathogenesis of human liver cancer. Also, we briefly describe the similarities between human and mouse HCC at the molecular level with emphasis on the advantages and disadvantages of each model. Although additional work is required, the data show that engineered mouse models have provided a significant contribution in our understanding of the pathogenesis of HCC. In particular, the mouse models have allowed the step-by-step analysis of the multiple stages of liver carcinogenesis with the identification of the underlying alterations in signal transduction pathways, cell cycle, and epigenetic and genetic mechanisms involved. Furthermore, the information obtained from these mouse models will help to design new, more specific and effective therapeutic approaches against human HCC. C1 [Calvisi, Diego F.] Ernst Moritz Arndt Univ Greifswald, Inst Pathol, D-17489 Greifswald, Germany. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Excellence Integrat Canc Biol & Genom Chief, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Calvisi, DF (reprint author), Ernst Moritz Arndt Univ Greifswald, Inst Pathol, Friedrich Loffler Str 23E, D-17489 Greifswald, Germany. EM diego.calvisi@uni-greifswald.de; valentina_factor@nih.gov; snorri_thorgeirsson@nih.gov; snorri_thorgeirsson@nih.gov NR 139 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6081-8 J9 CANCER GENET-SER JI Cancer Genetics PY 2011 BP 163 EP 188 DI 10.1007/978-1-4419-6082-5_9 D2 10.1007/978-1-4419-6082-5 PG 26 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA BSJ63 UT WOS:000284723700009 ER PT B AU Budhu, A Wang, XW AF Budhu, Anuradha Wang, Xin Wei BE Wang, XW Grisham, JW Thorgeirsson, SS TI Molecular Signatures of Hepatocellular Carcinoma Metastasis SO MOLECULAR GENETICS OF LIVER NEOPLASIA SE Cancer Genetics-Series LA English DT Article; Book Chapter DE Liver Cancer; Hepatocellular Carcinoma; Metastasis; Molecular signature; Microarray ID BREAST-CANCER METASTASIS; EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC LYMPHOCYTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; HUMAN LUNG CANCERS; GENE-EXPRESSION; MICRORNA EXPRESSION; TUMOR PROGRESSION; CAENORHABDITIS-ELEGANS; CHRONIC HEPATITIS AB Metastasis is a significant contributor to morbidity and mortality among cancer patients. Such patients are often considered incurable with treatments offering either supportive care or aggressive management without curative intent. Over the last several decades, research in the metastasis field has expanded our knowledge of cancer progression mechanisms; however, the translation of this knowledge into effective anti-metastasis therapies has not been swill. In fact, to add to the complexity of metastasis, recent findings have challenged the classic notion of clonal evolution whereby liver metastases develop during late stages of carcinogenesis. In this chapter, we evaluate several metastasis models and where applicable, describe how high-throughput molecular profiling technology has shed light on and provided prognostic value for this multifaceted process, with emphasis on the liver. The resolution of metastasis will have a large impact on clinical advances, specifically in targeted anti-metastasis therapies to benefit patients. C1 [Budhu, Anuradha] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Budhu, A (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4258,Bldg 37,Room 3044, Bethesda, MD 20892 USA. EM budhua@mail.nih.gov; xw3u@nih.gov; xw3u@nih.gov NR 106 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6081-8 J9 CANCER GENET-SER JI Cancer Genetics PY 2011 BP 241 EP 257 DI 10.1007/978-1-4419-6082-5_13 D2 10.1007/978-1-4419-6082-5 PG 17 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA BSJ63 UT WOS:000284723700013 ER PT B AU Marquardt, JU Thorgeirsson, SS AF Marquardt, Jens U. Thorgeirsson, Snorri S. BE Wang, XW Grisham, JW Thorgeirsson, SS TI Cancer Stem Cells and Liver Cancer SO MOLECULAR GENETICS OF LIVER NEOPLASIA SE Cancer Genetics-Series LA English DT Article; Book Chapter DE Liver cancer; HCC; Liver stem cells; Cancer stem cells; Tumor-initiating cells ID HEPATIC PROGENITOR CELLS; HEPATOCELLULAR-CARCINOMA CELLS; TUMOR-INITIATING CELLS; SIDE POPULATION CELLS; RAT-LIVER; DIFFERENTIATION THERAPY; EPITHELIAL-CELLS; DRUG-RESISTANCE; OVAL CELLS; PROSPECTIVE IDENTIFICATION AB The cancer stem-cell hypothesis proposes that tumors contain a distinct subpopulation of cells which are exclusively responsible for the initiation and maintenance of the cancer. These cells are referred to as either tumor-initiating cells or cancer stem cells (CSC). CSC were first identified in hematologic malignancies, but there is increasing evidence that variety of solid tumors (e.g., in breast, brain, pancreas, colon, and liver) are hierarchically organized and sustained by a distinct subpopulation of CSC. The frequency of CSC in solid tumors is variable indicating both biological variation and technical issues. The existence of CSC also poses a significant clinical challenge since CSC have been shown to be more resistant to chemotherapy and radiotherapy. Consequently, identification and prospective characterization of the CSC in liver cancer promises to have an enormous impact on the development of both, novel diagnostic and therapeutic approaches. This chapter will include a background on the general concept of CSC; a presentation of different isolation methods for CSC; a discussion on the putative origin of the CSC; and a critical discussion of selected recent publications dealing with the existence, identification, and elimination of human liver CSC. C1 [Marquardt, Jens U.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20982 USA. [Thorgeirsson, Snorri S.] NCI, Ctr Excellence Integrat Canc Biol & Genom Chief, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Marquardt, JU (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4140A,37 Convent Dr MSC 4262, Bethesda, MD 20982 USA. EM marquardtju@mail.nih.gov; snorri_thorgeirsson@nih.gov; snorri_thorgeirsson@nih.gov NR 111 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6081-8 J9 CANCER GENET-SER JI Cancer Genetics PY 2011 BP 279 EP 299 DI 10.1007/978-1-4419-6082-5_15 D2 10.1007/978-1-4419-6082-5 PG 21 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA BSJ63 UT WOS:000284723700015 ER PT J AU Swierczewska, M Lee, S Chen, XY AF Swierczewska, Magdalena Lee, Seulki Chen, Xiaoyuan TI Inorganic Nanoparticles for Multimodal Molecular Imaging SO MOLECULAR IMAGING LA English DT Review ID IRON-OXIDE NANOPARTICLES; WALLED CARBON NANOTUBES; MRI CONTRAST AGENTS; QUANTUM DOTS; IN-VIVO; MAGNETIC-RESONANCE; RAMAN-SPECTROSCOPY; NANOSPHERE LITHOGRAPHY; SILICA NANOPARTICLES; SHAPE CONTROL AB Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle-based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles. C1 [Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Biomed Engn, Stony Brook, NY 11794 USA. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM Seulki.Lee@nih.gov; Shawn.Chen@nih.gov FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-01] NR 80 TC 38 Z9 38 U1 6 U2 50 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD JAN-FEB PY 2011 VL 10 IS 1 BP 3 EP 16 DI 10.2310/7290.2011.00001 PG 14 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 762HQ UT WOS:000290466200002 PM 21303611 ER PT J AU Gao, RY Mukhopadhyay, P Mohanraj, R Wang, H Horvath, B Yin, S Pacher, P AF Gao, Rachel Yue Mukhopadhyay, Partha Mohanraj, Rajesh Wang, Hua Horvath, Bela Yin, Shi Pacher, Pal TI Resveratrol attenuates azidothymidine-induced cardiotoxicity by decreasing mitochondrial reactive oxygen species generation in human cardiomyocytes SO MOLECULAR MEDICINE REPORTS LA English DT Article DE resveratrol; azidothymidine; cell death; cardiomyocytes; reactive oxygen species ID ARTERIAL ENDOTHELIAL-CELLS; VASCULAR OXIDATIVE STRESS; NITRIC-OXIDE; IN-VIVO; INDUCED CARDIOMYOPATHY; SUPEROXIDE-PRODUCTION; LIVE CELLS; VITAMIN-C; TNF-ALPHA; RAT AB Nucleotide reverse transcriptase inhibitors, such as zidovudine (azidothymidine, AZT) and stavudine, represent a class of approved antiretroviral agents for highly active antiretroviral therapy, which prolongs the life expectancy of patients infected with human-immunodeficiency virus. Unfortunately, the use of these drugs is associated with known toxicities in the liver, skeletal muscle, heart and other organs, which may involve increased reactive oxygen species (ROS) generation, among other mechanisms. Resveratrol is a polyphenolic plant-derived antioxidant abundantly found in certain grapes, roots, berries, peanuts and red wine. This study, using primary human cardiomyocytes, evaluated the effects of AZT and pre-treatment with resveratrol on mitochondrial ROS generation and the cell death pathways. AZT induced concentration-dependent cell death, involving both caspase-3 and -7 and poly(ADP-ribose) polymerase activation, coupled with increased mitochonclrial ROS generation in human cardiomyocytes. These effects of AZT on mitochondrial ROS generation and cell death may be attenuated by resveratrol pre-treatment. The results demonstrate that mitochondrial ROS generation plays a pivotal role in the cardiotoxicity of AZT in human cardiomyocytes, and resveratrol may provide a potential strategy to attenuate these pathological alterations, which are associated with widely used antiretroviral therapy. C1 [Gao, Rachel Yue; Mukhopadhyay, Partha; Mohanraj, Rajesh; Horvath, Bela; Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Wang, Hua; Yin, Shi] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Horvath, Bela] Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413,Room 2N-17, Rockville, MD 20852 USA. EM pacher@mail.nih.gov RI Horvath, Bela/A-7368-2009; MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008; OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Gao, Yue/0000-0002-7890-1605 FU National Institutes of Health/NIAAA; Hungarian Scientific Research Foundation: NKTH-OTKA-EU [MB08A-80238] FX This study was supported by the Intramural Research Program of the National Institutes of Health/NIAAA (to P.P.). B.H. is a recipient of a Fellowship from the Hungarian Scientific Research Foundation: NKTH-OTKA-EU (MB08A-80238). NR 40 TC 15 Z9 17 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1791-2997 J9 MOL MED REP JI Mol. Med. Rep. PD JAN-FEB PY 2011 VL 4 IS 1 BP 151 EP 155 DI 10.3892/mmr.2010.390 PG 5 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA 707QM UT WOS:000286301100024 PM 21461578 ER PT J AU Babu, M Beloglazova, N Flick, R Graham, C Skarina, T Nocek, B Gagarinova, A Pogoutse, O Brown, G Binkowski, A Phanse, S Joachimiak, A Koonin, EV Savchenko, A Emili, A Greenblatt, J Edwards, AM Yakunin, AF AF Babu, Mohan Beloglazova, Natalia Flick, Robert Graham, Chris Skarina, Tatiana Nocek, Boguslaw Gagarinova, Alla Pogoutse, Oxana Brown, Greg Binkowski, Andrew Phanse, Sadhna Joachimiak, Andrzej Koonin, Eugene V. Savchenko, Alexei Emili, Andrew Greenblatt, Jack Edwards, Aled M. Yakunin, Alexander F. TI A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair SO MOLECULAR MICROBIOLOGY LA English DT Article ID PROVIDES ACQUIRED-RESISTANCE; INTERSTRAND CROSS-LINKS; DOUBLE-STRAND BREAKS; ESCHERICHIA-COLI; SULFOLOBUS-SOLFATARICUS; RECOMBINATIONAL REPAIR; CHROMOSOME SEGREGATION; HOLLIDAY JUNCTIONS; PROTEIN COMPLEXES; STATIONARY-PHASE AB P>Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks and 5'-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair. C1 [Babu, Mohan; Beloglazova, Natalia; Flick, Robert; Graham, Chris; Skarina, Tatiana; Gagarinova, Alla; Pogoutse, Oxana; Brown, Greg; Phanse, Sadhna; Savchenko, Alexei; Emili, Andrew; Greenblatt, Jack; Edwards, Aled M.; Yakunin, Alexander F.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. [Nocek, Boguslaw; Binkowski, Andrew; Joachimiak, Andrzej; Edwards, Aled M.] Argonne Natl Lab, Dept Biosci, Midwest Ctr Struct Genom, Argonne, IL 60439 USA. [Nocek, Boguslaw; Binkowski, Andrew; Joachimiak, Andrzej; Edwards, Aled M.] Argonne Natl Lab, Dept Biosci, Struct Biol Ctr, Argonne, IL 60439 USA. [Koonin, Eugene V.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Emili, Andrew; Greenblatt, Jack; Edwards, Aled M.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Edwards, Aled M.] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada. RP Yakunin, AF (reprint author), Univ Toronto, Banting & Best Dept Med Res, 112 Coll St, Toronto, ON M5G 1L6, Canada. EM andrew.emili@utoronto.ca; jack.greenblatt@utoronto.ca; aled.edwards@utoronto.ca; a.iakounine@utoronto.ca RI Yakunin, Alexander/J-1519-2014; OI Yakunin, Alexander/0000-0003-0813-6490 FU Government of Canada; Ontario Genomics Institute [2009-OGI-ABC-1405]; Canadian Institutes of Health Research [CIHR 82852]; National Institutes of Health [GM074942]; US Department of Energy, Office of Biological and Environmental Research [DE-AC02-06CH11357]; US Department of Health and Human services (NIH, National Library of Medicine) FX We thank members of the Emili and Greenblatt laboratories and of the Structural Proteomics in Toronto (SPiT) Centre for technical assistance. We are grateful to Paul Choi and Sunney Xie from Harvard University for providing us with the YFP-chloramphenicol resistance cassette. We thank Andrew Taylor and Gerry Smith from the Fred Hutchinson Cancer Research Center, Seattle, WA, for generous gifts of anti-RecBCD monoclonal antibodies. This work was supported by the Government of Canada through Genome Canada and the Ontario Genomics Institute (J.G., A.E. and A.F.Y.; 2009-OGI-ABC-1405), by the Canadian Institutes of Health Research Grant CIHR 82852 (to J.G. and A.E.), by the National Institutes of Health Grant GM074942 (to A.J.), and by the US Department of Energy, Office of Biological and Environmental Research, under contract DE-AC02-06CH11357 (to A.J.). E.V.K. is supported by the intramural funds of the US Department of Health and Human services (NIH, National Library of Medicine). NR 88 TC 101 Z9 119 U1 1 U2 31 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 2011 VL 79 IS 2 BP 484 EP 502 DI 10.1111/j.1365-2958.2010.07465.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 705FL UT WOS:000286114200017 PM 21219465 ER PT J AU Baxa, U Keller, PW Cheng, NQ Wall, JS Steven, AC AF Baxa, Ulrich Keller, Paul W. Cheng, Naiqian Wall, Joseph S. Steven, Alasdair C. TI In Sup35p filaments (the [PSI plus ] prion), the globular C-terminal domains are widely offset from the amyloid fibril backbone SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRANSMISSION ELECTRON-MICROSCOPY; RELEASE FACTOR ERF3; SACCHAROMYCES-CEREVISIAE; IN-VITRO; TRANSLATION TERMINATION; MASS ANALYSIS; MACROMOLECULAR COMPLEXES; FUNCTIONAL-ANALYSIS; CRYSTAL-STRUCTURE; MESSENGER-RNA AB P>In yeast cells infected with the [PSI+] prion, Sup35p forms aggregates and its activity in translation termination is downregulated. Transfection experiments have shown that Sup35p filaments assembled in vitro are infectious, suggesting that they reproduce or closely resemble the prion. We have used several EM techniques to study the molecular architecture of filaments, seeking clues as to the mechanism of downregulation. Sup35p has an N-terminal 'prion' domain; a highly charged middle (M-)domain; and a C-terminal domain with the translation termination activity. By negative staining, cryo-EM and scanning transmission EM (STEM), filaments of full-length Sup35p show a thin backbone fibril surrounded by a diffuse 65-nm-wide cloud of globular C-domains. In diameter (similar to 8 nm) and appearance, the backbones resemble amyloid fibrils of N-domains alone. STEM mass-per-unit-length data yield similar to 1 subunit per 0.47 nm for N-fibrils, NM-filaments and Sup35p filaments, further supporting the fibril backbone model. The 30 nm radial span of decorating C-domains indicates that the M-domains assume highly extended conformations, offering an explanation for the residual Sup35p activity in infected cells, whereby the C-domains remain free enough to interact with ribosomes. C1 [Baxa, Ulrich; Keller, Paul W.; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Wall, Joseph S.] Brookhaven Natl Labs, Dept Biol, Upton, NY 11973 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov FU NIAMS; USDOE-OHER FX We thank Ms B. Lin for STEM sample preparation and Dr M. Simon for STEM data collection, Drs B. Heymann and N. Mizuno for help with image analysis, and Dr D.C. Masison for helpful discussions. This work was supported by the Intramural Research Program of NIAMS. The BNL STEM is supported by USDOE-OHER. NR 58 TC 25 Z9 25 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2011 VL 79 IS 2 BP 523 EP 532 DI 10.1111/j.1365-2958.2010.07466.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 705FL UT WOS:000286114200019 PM 21219467 ER PT J AU Voyiaziakis, E Evgrafov, O Li, D Yoon, HJ Tabares, P Samuels, J Wang, Y Riddle, MA Grados, MA Bienvenu, OJ Shugart, YY Liang, KY Greenberg, BD Rasmussen, SA Murphy, DL Wendland, JR McCracken, JT Piacentini, J Rauch, SL Pauls, DL Nestadt, G Fyer, AJ Knowles, JA AF Voyiaziakis, E. Evgrafov, O. Li, D. Yoon, H-J Tabares, P. Samuels, J. Wang, Y. Riddle, M. A. Grados, M. A. Bienvenu, O. J. Shugart, Y. Y. Liang, K-Y Greenberg, B. D. Rasmussen, S. A. Murphy, D. L. Wendland, J. R. McCracken, J. T. Piacentini, J. Rauch, S. L. Pauls, D. L. Nestadt, G. Fyer, A. J. Knowles, J. A. TI Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study SO MOLECULAR PSYCHIATRY LA English DT Article DE OCD genetics; family study; affected sib-pair study; molecular haplotype analysis; serotonin transporter; heterogeneity analysis ID SEROTONIN TRANSPORTER GENE; NUMBER-TANDEM-REPEAT; COMPLEX SEGREGATION ANALYSIS; VARIABLE-NUMBER; TRANSMISSION DISEQUILIBRIUM; LINKAGE DISEQUILIBRIUM; POLYMORPHISM 5-HTTLPR; REGION POLYMORPHISM; PEDIATRIC PROBANDS; REGULATORY REGION AB Genetic association studies of SLC6A4 (SERT) and obsessive-compulsive disorder (OCD) have been equivocal. We genotyped 1241 individuals in 278 pedigrees from the OCD Collaborative Genetics Study for 13 single-nucleotide polymorphisms, for the linked polymorphic region (LPR) indel with molecular haplotypes at rs25531, for VNTR polymorphisms in introns 2 and 7 and for a 381-bp deletion 3' to the LPR. We analyzed using the Family-Based Association Test (FBAT) under additive, dominant, recessive and genotypic models, using both OCD and sex-stratified OCD as phenotypes. Two-point FBAT analysis detected association between Int2 (P = 0.0089) and Int7 (P = 0.0187) (genotypic model). Sex-stratified two-point analysis showed strong association in females with Int2 (P < 0.0002), significant after correction for linkage disequilibrium, and multiple marker and model testing (P(Adj) = 0.0069). The SLC6A4 gene is composed of two haplotype blocks (our data and the HapMap); FBAT whole-marker analysis conducted using this structure was not significant. Several noteworthy nonsignificant results have emerged. Unlike Hu et al., we found no evidence for overtransmission of the LPR L(A) allele (genotype relative risk = 1.11, 95% confidence interval: 0.77-1.60); however, rare individual haplotypes containing L(A) with P < 0.05 were observed. Similarly, three individuals (two with OCD/OCPD) carried the rare I425V SLC6A4 variant, but none of them passed it on to their six OCD-affected offspring, suggesting that it is unlikely to be solely responsible for the 'OCD plus syndrome', as reported by Ozaki et al. In conclusion, we found evidence of genetic association at the SLC6A4 locus with OCD. A noteworthy lack of association at the LPR, LPR-rs25531 and rare 425V variants suggests that hypotheses about OCD risk need revision to accommodate these new findings, including a possible gender effect. Molecular Psychiatry (2011) 16, 108-120; doi:10.1038/mp.2009.100; published online 6 October 2009 C1 [Voyiaziakis, E.; Evgrafov, O.; Knowles, J. A.] Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA. [Li, D.] Univ So Calif, Div Biostat, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Yoon, H-J; Knowles, J. A.] Univ So Calif, Zilkha Neurogenet Inst, Keck Sch Med, Los Angeles, CA 90089 USA. [Tabares, P.; Fyer, A. J.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA. [Tabares, P.; Fyer, A. J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Samuels, J.; Wang, Y.; Riddle, M. A.; Grados, M. A.; Bienvenu, O. J.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Shugart, Y. Y.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Liang, K-Y] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA. [Murphy, D. L.; Wendland, J. R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Voyiaziakis, E (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, MC-2821,1501 San Pablo,ZNI 401, Los Angeles, CA 90089 USA. EM emanuelv@keck.usc.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Wendland, Jens/A-1809-2012; OI Samuels, Jack/0000-0002-6715-7905 FU NIMH [R01 MH50214, K23-MH066284, K23-MH64543, MH079494, MH050214]; NIH/NCRR/OPD-GCRC [RR00052]; Obsessive Compulsive Foundation (OCF); USC, Keck School, Psychiatry; NARSAD; Neurogen; Sepracor; Novartis; Medtronic; Cyberonics; Cephalon; Northstar; Eli Lilly; Bristol Myers; Squibb; Seaside Pharmaceuticals; Aspect; CMREF FX This study is supported by NIMH R01 MH50214 and NIH/NCRR/OPD-GCRC RR00052 (GN). EV is a recipient of a 2006 grant award from the Obsessive Compulsive Foundation (OCF) and a departmental fellowship award (USC, Keck School, Psychiatry). OE received a Young Investigator Award from NARSAD. YYS initiated her contribution to this report while working at JHU, and is currently working at the Genomic Research Branch, NIMH. Part of this work was completed as her outside activity, and as such the views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the US Government. SAR and DLP are funded by the NIMH. SLR has received honoraria and/or consultation fees from Neurogen, Sepracor, Novartis and Medtronic, and has conducted research funded by Medtronic, Cyberonics, Cephalon and Northstar. JTM has received research support from Eli Lilly, Bristol Myers, Squibb, Seaside Pharmaceuticals, and Aspect. Other relevant NIMH awards: K23-MH066284 (MG) & K23-MH64543 (OJB). JAK is funded by the NIMH, CMREF and NARSAD, and this project was funded by NIMH grants MH079494 & MH050214. He is a member of the scientific advisory boards of SoftGenetics, Inc. & Life Technologies, Inc. and has received compensation from the latter. NR 71 TC 26 Z9 27 U1 3 U2 9 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 2011 VL 16 IS 1 BP 108 EP 120 DI 10.1038/mp.2009.100 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 697VE UT WOS:000285546400012 PM 19806148 ER PT J AU Hunter, MJ Tuschong, LM Fowler, CJ Bauer, TR Burkholder, TH Hickstein, DD AF Hunter, Michael J. Tuschong, Laura M. Fowler, Cedar J. Bauer, Thomas R., Jr. Burkholder, Tanya H. Hickstein, Dennis D. TI Gene Therapy of Canine Leukocyte Adhesion Deficiency Using Lentiviral Vectors With Human CD11b and CD18 Promoters Driving Canine CD18 Expression SO MOLECULAR THERAPY LA English DT Article ID BETA-SUBUNIT CD18; DISEASE PHENOTYPE; GLANZMANN THROMBASTHENIA; P150,95 GLYCOPROTEINS; RETROVIRAL VECTORS; INTEGRIN; ADHERENCE; LFA-1; IDENTIFICATION; MAC-1 AB To identify cellular promoters in a self-inactivating (SIN) lentiviral vector that might be beneficial in treating children with leukocyte adhesion deficiency type 1 (LAD-1), we tested lentiviral vectors with human CD11 and CD18 leukocyte integrin proximal promoter elements directing expression of canine CD18 in animals with canine LAD (CLAD). Lentiviral vectors with either the human CD11b (637 bp) proximal promoter or the human CD18 (1,060 bp) proximal promoter resulted in the highest percentages of CD18(+) CLAD CD34(+) cells in vitro. Subsequently, two CLAD dogs were infused with autologous CD34(+) cells transduced with the hCD11b (637 bp)-cCD18 vector, and two CLAD dogs were infused with autologous CD34(+) cells transduced with the hCD18 (1,060 bp)-cCD18 vector. Each dog received a nonmyeloablative dose of 200 cGy total body irradiation (TBI) before the infusion of transduced cells. The two CLAD dogs treated with the hCD18 (1,060 bp)-cCD18 vector, and one of the two dogs treated with the hCD11b (637 bp)-cCD18 vector, had reversal of the CLAD phenotype. These studies using endogenous leukocyte integrin proximal promoters represent an important step in the development of gene therapy for children with LAD-1. C1 [Hunter, Michael J.; Tuschong, Laura M.; Bauer, Thomas R., Jr.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fowler, Cedar J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Burkholder, Tanya H.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Hunter, MJ (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC1203,Bldg 10 CRC,Room 3-3264, Bethesda, MD 20892 USA. EM huntermj@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Veena Kapoor, NCI, for flow cytometry assistance. The authors have declared that no conflict of interest exists. NR 36 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2011 VL 19 IS 1 BP 113 EP 121 DI 10.1038/mt.2010.203 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 702BI UT WOS:000285869200015 PM 20859258 ER PT J AU Santilli, G Almarza, E Brendel, C Choi, U Beilin, C Blundell, MP Haria, S Parsley, KL Kinnon, C Malech, HL Bueren, JA Grez, M Thrasher, AJ AF Santilli, Giorgia Almarza, Elena Brendel, Christian Choi, Uimook Beilin, Chiara Blundell, Michael P. Haria, Sneha Parsley, Kathryn L. Kinnon, Christine Malech, Harry L. Bueren, Juan A. Grez, Manuel Thrasher, Adrian J. TI Biochemical Correction of X-CGD by a Novel Chimeric Promoter Regulating High Levels of Transgene Expression in Myeloid Cells SO MOLECULAR THERAPY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; GENE-THERAPY; NADPH OXIDASE; HEMATOPOIETIC-CELLS; SUPEROXIDE-PRODUCTION; GENOMIC INSTABILITY; HOST-DEFENSE; MOUSE MODEL; C-MYB; PU.1 AB X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase catalytic subunit gp91(phox). A recent clinical trial for X-CGD using a spleen focus-forming virus (SFFV)-based gamma-retroviral vector has demonstrated clear therapeutic benefits in several patients although complicated by enhancer-mediated mutagenesis and diminution of effectiveness over time due to silencing of the viral long terminal repeat (LTR). To improve safety and efficacy, we have designed a lentiviral vector that directs transgene expression primarily in myeloid cells. To this end, we created a synthetic chimeric promoter that contains binding sites for myeloid transcription factors CAAT box enhancer-binding family proteins (C/EBPs) and PU.1, which are highly expressed during granulocytic differentiation. As predicted, the chimeric promoter regulated higher reporter gene expression in myeloid than in nonmyeloid cells, and in human hematopoietic progenitors upon granulocytic differentiation. In a murine model of stem cell gene therapy for X-CGD, the chimeric vector resulted in high levels of gp91(phox) expression in committed myeloid cells and granulocytes, and restored normal NADPH-oxidase activity. These findings were recapitulated in human neutrophils derived from transduced X-CGD CD34(+) cells in vivo, and suggest that the chimeric promoter will have utility for gene therapy of myeloid lineage disorders such as CGD. C1 [Santilli, Giorgia; Beilin, Chiara; Blundell, Michael P.; Haria, Sneha; Parsley, Kathryn L.; Kinnon, Christine; Thrasher, Adrian J.] UCL, Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England. [Almarza, Elena; Bueren, Juan A.] CIEMAT, Hematopoiesis & Gene Therapy Div, E-28040 Madrid, Spain. [Almarza, Elena; Bueren, Juan A.] Networking Ctr Biomed Res Rare Dis CIBERER, E-28040 Madrid, Spain. [Brendel, Christian; Grez, Manuel] Georg Speyer Haus, Biomed Res Inst, Frankfurt, Germany. [Choi, Uimook; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Thrasher, AJ (reprint author), UCL, Inst Child Hlth, Mol Immunol Unit, 30 Guilford St, London WC1N 1EH, England. EM a.thrasher@ich.ucl.ac.uk RI Kinnon, Christine/A-1585-2010; Almarza, Elena/K-6010-2014; Bueren, Juan/L-6112-2014; OI Almarza, Elena/0000-0002-4414-3455; Bueren, Juan/0000-0002-3228-7013; Malech, Harry/0000-0001-5874-5775 FU Chronic Granulomatous Disorder Research Trust, London [J4G/04B/GT]; Deutsche Forschungsgemeinschaft (Bonn, Germany) [GRK 1172]; Spanish government; Ministerio de Ciencia e Innovacion [LE2009/0100, SAF2009-07164]; European Program PERSIST; Fondo de Investigaciones Sanitarias [RETIC-RD06/241]; Fundacion Marcelino Botin FX A.J.T. is a Wellcome Trust Senior Clinical Fellow, and NIHR Senior Investigator. This work was supported by the Chronic Granulomatous Disorder Research Trust, London (grant J4G/04B/GT); C.B. was supported by the Deutsche Forschungsgemeinschaft (Bonn, Germany) within the graduate study program GRK 1172"Biologicals". E.A. was supported partially by the Spanish network CIBERER plus a grant given by the Jose Castillejo program of the Spanish government. J.A.B. was supported by grants from Ministerio de Ciencia e Innovacion (Grants PLE2009/0100 and SAF2009-07164); European Program PERSIST; Fondo de Investigaciones Sanitarias (RETIC-RD06/241) and Fundacion Marcelino Botin. NR 45 TC 56 Z9 56 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2011 VL 19 IS 1 BP 122 EP 132 DI 10.1038/mt.2010.226 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 702BI UT WOS:000285869200016 PM 20978475 ER PT J AU Uchida, N Washington, KN Lap, CJ Hsieh, MM Tisdale, JF AF Uchida, Naoya Washington, Kareem N. Lap, Coen J. Hsieh, Matthew M. Tisdale, John F. TI Chicken HS4 Insulators Have Minimal Barrier Function Among Progeny of Human Hematopoietic Cells Transduced With an HIV1-based Lentiviral Vector SO MOLECULAR THERAPY LA English DT Article ID HUMAN BETA-GLOBIN; GENE-THERAPY; RETROVIRUS VECTORS; FETAL-HEMOGLOBIN; HIV-1 INFECTION; NUCLEAR IMPORT; MOUSE MODEL; STEM-CELLS; EXPRESSION; THALASSEMIA AB Position effects limit the curative potential of gene transfer strategies for the hemoglobinopathies by inducing clonal variability of transgene expression. We evaluated the mitigating effects of the chicken hypersensitivity site 4 (HS4) insulator among lentiviral vector-transduced human hematopoietic cells. We constructed various lentiviral vectors using a green fluorescent protein (GFP) reporter under the control of a reverse-oriented murine stem cell virus (MSCV)-long-term repeat (LTR) promoter or a reverse-oriented beta-globin expression cassette. A full-length HS4, a tandem HS4 core, and a single core insulator were inserted into the 3' LTR in both forward and reverse orientation. All but the reverse single core insulator significantly decreased titers. All reduced %GFP without increasing mean fluorescence intensity (MFI) among erythroid progeny of transduced human CD34(+) cells. A lower coefficient of variation (CV) was observed only among progeny of the full-length vector-transduced cells, yet a fivefold reduction in transduction efficiency was observed. In xenografted mice, the single core insulator decreased both the %GFP and the MFI at 4 and 8 weeks after transplantation with no difference in CVs. These data demonstrate that the inclusion of HS4 insulator elements lowers viral titers, reduces efficiency of transduction, and produces minimal effects on transgene expression among human hematopoietic cells in vitro and in vivo. C1 [Uchida, Naoya; Washington, Kareem N.; Lap, Coen J.; Hsieh, Matthew M.; Tisdale, John F.] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD 20892 USA. EM johntis@mail.nih.gov OI Lap, Coen/0000-0001-6815-0695 FU National Heart, Lung, and Blood Institute (NHLBI); National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) FX This work was supported by the intramural research program of the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) at the National Institutes of Health. NR 37 TC 17 Z9 17 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2011 VL 19 IS 1 BP 133 EP 139 DI 10.1038/mt.2010.218 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 702BI UT WOS:000285869200017 PM 20940706 ER PT J AU Li, B Peet, NP Butler, MM Burnett, JC Moir, DT Bowlin, TL AF Li, Bing Peet, Norton P. Butler, Michelle M. Burnett, James C. Moir, Donald T. Bowlin, Terry L. TI Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication SO MOLECULES LA English DT Review DE botulinum neurotoxin; inhibitor; drug discovery ID FUNCTION-ORIENTED SYNTHESIS; TOXIN TYPE-A; LIGHT-CHAIN; CLOSTRIDIUM-BOTULINUM; SEROTYPE-A; STRUCTURAL-ANALYSIS; NEUROTRANSMITTER RELEASE; SUBSTRATE RECOGNITION; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE AB Botulinum neurotoxins (BoNTs) are the most potent of known toxins and are listed as category A biothreat agents by the U. S. CDC. The BoNT-mediated proteolysis of SNARE proteins inhibits the exocytosis of acetylcholine into neuromuscular junctions, leading to life-threatening flaccid paralysis. Currently, the only therapy for BoNT intoxication (which results in the disease state botulism) includes experimental preventative antibodies and long-term supportive care. Therefore, there is an urgent need to identify and develop inhibitors that will serve as both prophylactic agents and post-exposure 'rescue' therapeutics. This review focuses on recent progress to discover and develop small molecule inhibitors as therapeutic countermeasures for BoNT intoxication. C1 [Li, Bing; Peet, Norton P.; Butler, Michelle M.; Moir, Donald T.; Bowlin, Terry L.] Microbiotix Inc, Worcester, MA 01605 USA. [Burnett, James C.] NCI, SAIC Frederick Inc, Structure Based Drug Discovery Grp, Frederick, MD 21702 USA. RP Li, B (reprint author), Microbiotix Inc, 1Innovat Dr, Worcester, MA 01605 USA. EM bli@microbiotix.com; burnettjames@mail.nih.gov NR 88 TC 17 Z9 17 U1 0 U2 9 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD JAN PY 2011 VL 16 IS 1 BP 202 EP 220 DI 10.3390/molecules16010202 PG 19 WC Chemistry, Organic SC Chemistry GA 711MT UT WOS:000286596400015 PM 21193845 ER PT J AU La Merrill, M Birnbaum, LS AF La Merrill, Michele Birnbaum, Linda S. TI Childhood Obesity and Environmental Chemicals SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE environmental exposure; growth and development; obesity ID POLYBROMINATED DIPHENYL ETHERS; PERSISTENT ORGANIC POLLUTANTS; BODY-MASS INDEX; ENDOPLASMIC-RETICULUM STRESS; NUTRITION EXAMINATION SURVEY; RECEPTOR-GAMMA AGONIST; SPRAGUE-DAWLEY RATS; FAT-CELL TURNOVER; BISPHENOL-A; METABOLIC SYNDROME AB Childhood and adolescent rates of obesity and overweight are continuing to increase in much of the world. Risk. factors such as diet composition, excess caloric intake, decreased exercise, genetics, and the built environment are active areas of etiologic research. The obesogen hypothesis, which postulates that prenatal and perinatal chemical exposure can contribute to risk of childhood and adolescent obesity, remains relatively underexamined. This review surveys numerous classes of chemicals for which this hypothesis has been explored. We focus on human data where they exist and also discuss the findings of rodent and cell culture studies. Organochlorine chemicals as well as several classes of chemicals that are peroxisome proliferator-activated receptor agonists are identified as possible risk factors for obesity. Recommendations for future epidemiologic and experimental research on the chemical origins of obesity are also given. Mt Sinai J Med 78:22-48, 2011. (C) 2011 Mount Sinai School of Medicine C1 [La Merrill, Michele] Mt Sinai Sch Med, New York, NY 10029 USA. [Birnbaum, Linda S.] NIEHS, NCI, Res Triangle Pk, NC USA. RP La Merrill, M (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. EM Michele.LaMerrill@mssm.edu FU National Institutes of Health [ML: T32HD049311] FX This research was funded by the Research Training Program in Environmental Pediatrics of the National Institutes of Health (ML: T32HD049311). NR 189 TC 42 Z9 45 U1 4 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD JAN-FEB PY 2011 VL 78 IS 1 BP 22 EP 48 DI 10.1002/msj.20229 PG 27 WC Medicine, General & Internal SC General & Internal Medicine GA 717BN UT WOS:000287017300003 PM 21259261 ER PT J AU Hirschfeld, S Songco, D Kramer, BS Guttmacher, AE AF Hirschfeld, Steven Songco, David Kramer, Barnett S. Guttmacher, Alan E. TI National Children's Study: Update in 2010 SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE cohort study; genetics; environmental exposures; childhood development; health determinants; study recruitment ID SAMPLE AB The National Children's Study will examine the effects of the environment and genetics on the growth, development, and health of children across the United States; it will follow participants from before birth until age 21 years. The goal of the study is to improve the health and well-being of children and contribute to understanding the roles various factors play in health and disease. Findings from the study will be made available as the research progresses, making potential benefits known to the public as soon as possible. A robust pilot study, or Vanguard Study, is underway to generate data for designing the subsequent Main Study. The goals of the Vanguard Study are feasibility, acceptability, and cost, and the goals of the Main Study will be exposure-response relationships and biological, environmental, and genetic interactions. The initial Vanguard Study experience among 7 study centers was successful in many ways, including delineating the topics to explore for the next phase of the Vanguard Study. Three different recruitment strategies are under evaluation to determine what approach to use for the Main Study. The organization of National Children's Study operations is currently based on a new decentralized business model. Mt Sinai J Med 78:119-125, 2011. (C) 2011 Mount Sinai School of Medicine C1 [Hirschfeld, Steven; Songco, David; Guttmacher, Alan E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Kramer, Barnett S.] NIH, Off Director, Rockville, MD USA. RP Hirschfeld, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. EM hirschfs@mail.nih.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 FU Office of the Director of the National Institutes of Health FX This analysis was conducted as part of the National Children's Study, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and funded, through its appropriation, by the Office of the Director of the National Institutes of Health NR 3 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD JAN-FEB PY 2011 VL 78 IS 1 BP 119 EP 125 DI 10.1002/msj.20227 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 717BN UT WOS:000287017300010 PM 21259268 ER PT J AU Smith, PD Smythies, LE Shen, R Greenwell-Wild, T Gliozzi, M Wahl, SM AF Smith, P. D. Smythies, L. E. Shen, R. Greenwell-Wild, T. Gliozzi, M. Wahl, S. M. TI Intestinal macrophages and response to microbial encroachment SO MUCOSAL IMMUNOLOGY LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; IMMUNODEFICIENCY-VIRUS TYPE-1; GROWTH-FACTOR-BETA; REGULATORY T-CELLS; IMMUNE-DEFICIENCY-SYNDROME; GENOME-WIDE ASSOCIATION; TOLL-LIKE RECEPTORS; CROHNS-DISEASE; TGF-BETA; HIV-1 INFECTION AB Macrophages in the gastrointestinal mucosa represent the largest pool of tissue macrophages in the body. In order to maintain mucosal homeostasis, resident intestinal macrophages uniquely do not express the lipopolysaccharide (LPS) co-receptor CD14 or the IgA (CD89) and IgG (CD16, 32, and 64) receptors, yet prominently display Toll-like receptors (TLRs) 3 -9. Remarkably, intestinal macrophages also do not produce proinflammatory cytokines in response to TLR ligands, likely because of extracellular matrix (stromal) transforming growth factor-beta (TGF-beta) dysregulation of nuclear factor (NF)-kappa B signal proteins and, via Smad signaling, expression of I kappa B alpha, thereby inhibiting NF-kappa-B-mediated activities. Thus, in noninflamed mucosa, resident macrophages are inflammation anergic but retain avid scavenger and host defense function, an ideal profile for macrophages in close proximity to gut microbiota. In the event of impaired epithelial integrity during intestinal infection or inflammation, however, blood monocytes also accumulate in the lamina propria and actively pursue invading microorganisms through uptake and degradation of the organism and release of inflammatory mediators. Consequently, resident intestinal macrophages are inflammation adverse, but when the need arises, they receive assistance from newly recruited circulating monocytes. C1 [Smith, P. D.; Smythies, L. E.; Shen, R.] Univ Alabama Birmingham, Dept Med Gastroenterol, Birmingham, AL 35294 USA. [Greenwell-Wild, T.; Gliozzi, M.; Wahl, S. M.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Smith, PD (reprint author), Univ Alabama Birmingham, Dept Med Gastroenterol, Birmingham, AL 35294 USA. EM pdsmith@uab.edu; smwahl@dir.nidcr.nih.gov FU National Institutes of Health [DK-47322, DK-54495, AI-83027, AI-83539, DK-84063, AI-74438, RR-20136]; University of Alabama at Birmingham Mucosal HIV and Immunobiology Cente [DK-64400]; Crohn's and Colitis Foundation of America; National Institutes of Health FX We are grateful to Calley Grace for editorial assistance and Dr J. Orenstein for tissue biopsies. This work was supported by the National Institutes of Health (DK-47322, DK-54495, AI-83027, AI-83539, DK-84063, AI-74438, and RR-20136), the University of Alabama at Birmingham Mucosal HIV and Immunobiology Center (DK-64400), the Crohn's and Colitis Foundation of America, the Research Service of the Veterans Administration, and the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research, Bethesda, MD. NR 133 TC 120 Z9 124 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2011 VL 4 IS 1 BP 31 EP 42 DI 10.1038/mi.2010.66 PG 12 WC Immunology SC Immunology GA 700CC UT WOS:000285708900006 PM 20962772 ER PT J AU Saba, E Grivel, JC Vanpouille, C Brichacek, B Fitzgerald, W Margolis, L Lisco, A AF Saba, E. Grivel, J-C Vanpouille, C. Brichacek, B. Fitzgerald, W. Margolis, L. Lisco, A. TI Response to "The "gatekeeper" hypothesis challenged in a human cervico-vaginal tissue model for HIV-1 transmission" SO MUCOSAL IMMUNOLOGY LA English DT Letter ID SEXUAL TRANSMISSION; INFECTION C1 [Saba, E.; Grivel, J-C; Vanpouille, C.; Brichacek, B.; Fitzgerald, W.; Margolis, L.; Lisco, A.] Eunice Kennedy Shriver Natl Inst Child & Human De, Sect Intercellular Interact, Program Phys Biol, NIH, Bethesda, MD USA. [Saba, E.] San Raffaele Vita Salute Univ, AIDS Immunopathogenesis Unit, Milan, Italy. RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child & Human De, Sect Intercellular Interact, Program Phys Biol, NIH, Bethesda, MD USA. EM margolil@mail.nih.gov; liscoa@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JAN PY 2011 VL 4 IS 1 BP 122 EP 123 DI 10.1038/mi.2010.48 PG 3 WC Immunology SC Immunology GA 700CC UT WOS:000285708900015 ER PT J AU Raja, HA Schoch, CL Hustad, VP Shearer, CA Miller, AN AF Raja, Huzefa A. Schoch, Conrad L. Hustad, Vincent P. Shearer, Carol A. Miller, Andrew N. TI Testing the phylogenetic utility of MCM7 in the Ascomycota SO MYCOKEYS LA English DT Article DE Fungi; Leotiomyceta; MS456; non-lichenized ascomycetes; systematics; 28S nrDNA AB The Ascomycota are a group of filamentous fungi that occur as saprobes, pathogens, and symbionts. They are of immense industrial, medical, ecological, and economical importance. The search for new markers appropriate for molecular phylogenetic analysis of Ascomycota remains a challenging problem. In this study, we explore the phylogenetic utility of a single copy protein-coding gene, MCM7; newly recognized as useful for inferring phylogenetic relationships among the major classes of the Ascomycota. Our specific goals were to: 1) test the phylogenetic utility of MCM7 for estimating phylogenies at various taxonomic ranks (class and below) with an emphasis on non-lichenized ascomycetes; and, 2) compare the congruence, robustness and resolving power of MCM7-based phylogenies with that of nuclear large subunit rDNA (LSU)-based phylogenies for the same taxon set. A dataset of sequence data for MCM7 as well as LSU was assembled for 80 species belonging to 63 genera of lichenized and non-lichenized ascomycetes in the classes Dothideomycetes, Eurotiomycetes, Geoglossomycetes, Lecanoromycetes, Leotiomycetes, and Sordariomycetes. We obtained 93 new sequences of which 65 are MCM7 and 28 are LSU. Maximum-Likelihood and Bayesian analyses were performed using single as well as combined gene datasets and partitions. We also assessed substitution saturation for the MCM7 gene. Results indicate that MCM7 can be used successfully for determining phylogenetic relationships of ascomycetes and provided good resolution and support at half the cost compared to LSU. Phylogenetic informativeness profiles showed that MCM7 was more phylogenetically informative than LSU. The MCM7 gene is also a valuable phylogenetic marker for both lower as well as higher level phylogenetic analyses within the Ascomycota, especially when used in combination with the LSU gene. We found that although the third codon position of MCM7 is saturated, it was better to analyze the dataset with all codon positions included. Phylogenetic performance of MCM7 with and without the third codon position is discussed. C1 [Raja, Huzefa A.; Shearer, Carol A.] Univ Illinois, Dept Plant Biol, Urbana, IL 61801 USA. [Raja, Huzefa A.] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27402 USA. [Schoch, Conrad L.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Hustad, Vincent P.; Miller, Andrew N.] Univ Illinois, Illinois Nat Hist Survey, Champaign, IL 61820 USA. RP Raja, HA (reprint author), Univ Illinois, Dept Plant Biol, 505 S Goodwin Ave, Urbana, IL 61801 USA. EM haraja@uncg.edu FU National Science Foundation Grant (NSF) [DEB-08-44722]; NSF Grant [DEB-05-1558]; National Institutes of Health, National Library of Medicine FX This work was supported by the National Science Foundation Grant (NSF) DEB-08-44722 to CAS and ANM and in part by a NSF Grant DEB-05-1558 to ANM. CLS was also supported in part by the Intramural Research program of the National Institutes of Health, National Library of Medicine. We would also like to thank Astrid Ferrer, Jack Rogers and Sabine M. Huhndorf for providing some of the taxa and/or cultures used in this study. Any opinions, findings and conclusions or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the National Science Foundation. NR 95 TC 27 Z9 27 U1 0 U2 2 PU PENSOFT PUBL PI SOFIA PA GEO MILEV STR 13A, SOFIA, 1111, BULGARIA SN 1314-4057 EI 1314-4049 J9 MYCOKEYS JI MycoKeys PY 2011 IS 1 BP 63 EP 94 DI 10.3897/mycokeys.1.1966 PG 32 WC Mycology SC Mycology GA V39TR UT WOS:000209433800008 ER PT J AU Cai, WB Chen, XY AF Cai, Weibo Chen, Xiaoyuan BE Goins, BA Phillips, WT TI QUANTUM DOT-BASED MULTIMODALITY IMAGING AGENTS SO NANOIMAGING SE Pan Stanford Series on Biomedical Nanotechnology LA English DT Article; Book Chapter ID RESONANCE ENERGY-TRANSFER; IN-SITU HYBRIDIZATION; POSITRON-EMISSION-TOMOGRAPHY; ENDOTHELIAL GROWTH-FACTOR; TUMOR VASCULATURE; LIVING SUBJECTS; CONTRAST AGENT; LIVE CELLS; SEMICONDUCTOR NANOCRYSTALS; BIOLOGICAL DETECTION C1 [Cai, Weibo] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Cai, Weibo] Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Cai, Weibo] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI USA. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Cai, WB (reprint author), Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. EM wcai@uwhealth.org; shawn.chen@nih.gov NR 135 TC 0 Z9 0 U1 0 U2 0 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-9-81426-791-5 J9 PAN ST SER BIOM NANO PY 2011 VL 2 BP 129 EP 153 D2 10.4032/9789814267915 PG 25 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BXV61 UT WOS:000297273700007 ER PT J AU Longmire, MR Choyke, PL Kobayashi, H AF Longmire, Michelle R. Choyke, Peter L. Kobayashi, Hisataka BE Goins, BA Phillips, WT TI MULTIMODAL IMAGING OF DENDRIMERS SO NANOIMAGING SE Pan Stanford Series on Biomedical Nanotechnology LA English DT Article; Book Chapter ID MRI CONTRAST AGENTS; ACUTE-RENAL-FAILURE; DYNAMIC MICRO-MRI; MAGNETIC-RESONANCE; IN-VIVO; PAMAM DENDRIMERS; PHARMACOKINETIC PROPERTIES; MONOCLONAL-ANTIBODY; GOLD NANOPARTICLES; CANCER-TREATMENT C1 [Longmire, Michelle R.; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Longmire, MR (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayashi@mail.nih.gov NR 57 TC 0 Z9 0 U1 0 U2 0 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-9-81426-791-5 J9 PAN ST SER BIOM NANO PY 2011 VL 2 BP 155 EP 169 D2 10.4032/9789814267915 PG 15 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Research & Experimental Medicine; Radiology, Nuclear Medicine & Medical Imaging GA BXV61 UT WOS:000297273700008 ER PT B AU Chen, XY AF Chen, Xiaoyuan BE Chen, X TI NANOPLATFORM-BASED MOLECULAR IMAGING PREFACE SO NANOPLATFORM-BASED MOLECULAR IMAGING LA English DT Editorial Material; Book Chapter C1 [Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Chen, Xiaoyuan] Stanford Univ, Bio X Program, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. RP Chen, XY (reprint author), Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-76703-0; 978-0-470-52115-1 PY 2011 BP IX EP X D2 10.1002/9780470767047 PG 2 WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BA5SW UT WOS:000336989900001 ER PT B AU Gao, JH Xie, J Xu, B Chen, XY AF Gao, Jinhao Xie, Jin Xu, Bing Chen, Xiaoyuan BE Chen, X TI Synthesis of Nanomaterials as a Platform for Molecular Imaging SO NANOPLATFORM-BASED MOLECULAR IMAGING LA English DT Article; Book Chapter ID SHAPE-CONTROLLED SYNTHESIS; ONE-POT REACTION; SOLUBLE MAGNETITE NANOCRYSTALS; COLLOIDAL CHEMICAL-SYNTHESIS; SIZE-CONTROLLED SYNTHESIS; IRON-OXIDE NANOPARTICLES; CORE-SHELL NANOCRYSTALS; QUANTUM DOTS; IN-VIVO; OPTICAL-PROPERTIES C1 [Gao, Jinhao; Xie, Jin; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Gao, Jinhao; Xie, Jin; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Bio X Program, Stanford, CA 94305 USA. [Xie, Jin; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. [Xu, Bing] Brandeis Univ, Dept Chem, Waltham, MA 02254 USA. RP Gao, JH (reprint author), Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. NR 113 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-76703-0; 978-0-470-52115-1 PY 2011 BP 25 EP 45 D2 10.1002/9780470767047 PG 21 WC Nanoscience & Nanotechnology; Radiology, Nuclear Medicine & Medical Imaging SC Science & Technology - Other Topics; Radiology, Nuclear Medicine & Medical Imaging GA BA5SW UT WOS:000336989900003 ER EF