FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Madej, T
Lanczycki, CJ
Zhang, DC
Thiessen, PA
Geer, RC
Marchler-Bauer, A
Bryant, SH
AF Madej, Thomas
Lanczycki, Christopher J.
Zhang, Dachuan
Thiessen, Paul A.
Geer, Renata C.
Marchler-Bauer, Aron
Bryant, Stephen H.
TI MMDB and VAST+: tracking structural similarities between macromolecular
complexes
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID T-CELL-RECEPTOR; STRUCTURE ALIGNMENT; 3D STRUCTURES; PROTEINS;
SEQUENCES; ACCURACY; DATABASE; PEPTIDE; TCR
AB The computational detection of similarities between protein 3D structures has become an indispensable tool for the detection of homologous relationships, the classification of protein families and functional inference. Consequently, numerous algorithms have been developed that facilitate structure comparison, including rapid searches against a steadily growing collection of protein structures. To this end, NCBI's Molecular Modeling Database (MMDB), which is based on the Protein Data Bank (PDB), maintains a comprehensive and up-to-date archive of protein structure similarities computed with the Vector Alignment Search Tool (VAST). These similarities have been recorded on the level of single proteins and protein domains, comprising in excess of 1.5 billion pairwise alignments. Here we present VAST+, an extension to the existing VAST service, which summarizes and presents structural similarity on the level of biological assemblies or macromolecular complexes. VAST+ simplifies structure neighboring results and shows, for macromolecular complexes tracked in MMDB, lists of similar complexes ranked by the extent of similarity. VAST+ replaces the previous VAST service as the default presentation of structure neighboring data in NCBI's Entrez query and retrieval system. MMDB and VAST+ can be accessed via http://www.ncbi.nlm.nih.gov/Structure.
C1 [Madej, Thomas; Lanczycki, Christopher J.; Zhang, Dachuan; Thiessen, Paul A.; Geer, Renata C.; Marchler-Bauer, Aron; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Madej, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM madej@ncbi.nlm.nih.gov
OI Marchler-Bauer, Aron/0000-0003-1516-0712
FU Intramural Research Program of the National Library of Medicine at the
National Institutes of Health/DHHS
FX Intramural Research Program of the National Library of Medicine at
National Institutes of Health/DHHS. Comments, suggestions and questions
are welcome and should be directed to: info@ncbi.nlm.nih.gov. Funding
for open access charge: Intramural Research Program of the National
Library of Medicine at the National Institutes of Health/DHHS.
NR 26
TC 33
Z9 35
U1 3
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2014
VL 42
IS D1
BP D297
EP D303
DI 10.1093/nar/gkt1208
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5LF
UT WOS:000331139800045
PM 24319143
ER
PT J
AU Pruitt, KD
Brown, GR
Hiatt, SM
Thibaud-Nissen, F
Astashyn, A
Ermolaeva, O
Farrell, CM
Hart, J
Landrum, MJ
McGarvey, KM
Murphy, MR
O'Leary, NA
Pujar, S
Rajput, B
Rangwala, SH
Riddick, LD
Shkeda, A
Sun, HZ
Tamez, P
Tully, RE
Wallin, C
Webb, D
Weber, J
Wu, WD
DiCuccio, M
Kitts, P
Maglott, DR
Murphy, TD
Ostell, JM
AF Pruitt, Kim D.
Brown, Garth R.
Hiatt, Susan M.
Thibaud-Nissen, Francoise
Astashyn, Alexander
Ermolaeva, Olga
Farrell, Catherine M.
Hart, Jennifer
Landrum, Melissa J.
McGarvey, Kelly M.
Murphy, Michael R.
O'Leary, Nuala A.
Pujar, Shashikant
Rajput, Bhanu
Rangwala, Sanjida H.
Riddick, Lillian D.
Shkeda, Andrei
Sun, Hanzhen
Tamez, Pamela
Tully, Raymond E.
Wallin, Craig
Webb, David
Weber, Janet
Wu, Wendy
DiCuccio, Michael
Kitts, Paul
Maglott, Donna R.
Murphy, Terence D.
Ostell, James M.
TI RefSeq: an update on mammalian reference sequences
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DATABASE; RESOURCES; DISEASE; NCBI; DNA
AB The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database is a collection of annotated genomic, transcript and protein sequence records derived from data in public sequence archives and from computation, curation and collaboration (http://www.ncbi.nlm.nih.gov/refseq/). We report here on growth of the mammalian and human subsets, changes to NCBI's eukaryotic annotation pipeline and modifications affecting transcript and protein records. Recent changes to NCBI's eukaryotic genome annotation pipeline provide higher throughput, and the addition of RNAseq data to the pipeline results in a significant expansion of the number of transcripts and novel exons annotated on mammalian RefSeq genomes. Recent annotation changes include reporting supporting evidence for transcript records, modification of exon feature annotation and the addition of a structured report of gene and sequence attributes of biological interest. We also describe a revised protein annotation policy for alternatively spliced transcripts with more divergent predicted proteins and we summarize the current status of the RefSeqGene project.
C1 [Pruitt, Kim D.; Brown, Garth R.; Hiatt, Susan M.; Thibaud-Nissen, Francoise; Astashyn, Alexander; Ermolaeva, Olga; Farrell, Catherine M.; Hart, Jennifer; Landrum, Melissa J.; McGarvey, Kelly M.; Murphy, Michael R.; O'Leary, Nuala A.; Pujar, Shashikant; Rajput, Bhanu; Rangwala, Sanjida H.; Riddick, Lillian D.; Shkeda, Andrei; Sun, Hanzhen; Tamez, Pamela; Tully, Raymond E.; Wallin, Craig; Webb, David; Weber, Janet; Wu, Wendy; DiCuccio, Michael; Kitts, Paul; Maglott, Donna R.; Murphy, Terence D.; Ostell, James M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM pruitt@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 24
TC 336
Z9 338
U1 2
U2 20
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2014
VL 42
IS D1
BP D756
EP D763
DI 10.1093/nar/gkt1114
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5LF
UT WOS:000331139800112
PM 24259432
ER
PT J
AU Tatusova, T
Ciufo, S
Fedorov, B
O'Neill, K
Tolstoy, I
AF Tatusova, Tatiana
Ciufo, Stacy
Fedorov, Boris
O'Neill, Kathleen
Tolstoy, Igor
TI RefSeq microbial genomes database: new representation and annotation
strategy
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID WHOLE-GENOME; SEQUENCE; COMMUNITY; TOOL
AB The source of the microbial genomic sequences in the RefSeq collection is the set of primary sequence records submitted to the International Nucleotide Sequence Database public archives. These can be accessed through the Entrez search and retrieval system at http://www.ncbi.nlm.nih.gov/genome. Next-generation sequencing has enabled researchers to perform genomic sequencing at rates that were unimaginable in the past. Microbial genomes can now be sequenced in a matter of hours, which has led to a significant increase in the number of assembled genomes deposited in the public archives. This huge increase in DNA sequence data presents new challenges for the annotation, analysis and visualization bioinformatics tools. New strategies have been developed for the annotation and representation of reference genomes and sequence variations derived from population studies and clinical outbreaks.
C1 [Tatusova, Tatiana; Ciufo, Stacy; Fedorov, Boris; O'Neill, Kathleen; Tolstoy, Igor] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Tatusova, T (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM tatiana@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX Funding for open access charge: Intramural Research Program of the
National Institutes of Health, National Library of Medicine.
NR 20
TC 102
Z9 102
U1 3
U2 24
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2014
VL 42
IS D1
BP D553
EP D559
DI 10.1093/nar/gkt1274
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5LF
UT WOS:000331139800082
PM 24316578
ER
PT J
AU Tryka, KA
Hao, LN
Sturcke, A
Jin, YM
Wang, ZY
Ziyabari, L
Lee, M
Popova, N
Sharopova, N
Kimura, M
Feolo, M
AF Tryka, Kimberly A.
Hao, Luning
Sturcke, Anne
Jin, Yumi
Wang, Zhen Y.
Ziyabari, Lora
Lee, Moira
Popova, Natalia
Sharopova, Nataliya
Kimura, Masato
Feolo, Michael
TI NCBI's Database of Genotypes and Phenotypes: dbGaP
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
AB The Database of Genotypes and Phenotypes (dbGap, http://www.ncbi.nlm.nih.gov/gap) is a National Institutes of Health-sponsored repository charged to archive, curate and distribute information produced by studies investigating the interaction of genotype and phenotype. Information in dbGaP is organized as a hierarchical structure and includes the accessioned objects, phenotypes (as variables and datasets), various molecular assay data (SNP and Expression Array data, Sequence and Epigenomic marks), analyses and documents. Publicly accessible metadata about submitted studies, summary level data, and documents related to studies can be accessed freely on the dbGaP website. Individual-level data are accessible via Controlled Access application to scientists across the globe.
C1 [Tryka, Kimberly A.; Hao, Luning; Sturcke, Anne; Jin, Yumi; Wang, Zhen Y.; Ziyabari, Lora; Lee, Moira; Popova, Natalia; Sharopova, Nataliya; Kimura, Masato; Feolo, Michael] Natl Lib Med, Natl Ctr Biotechnol Informat, Informat Engn Branch, Bethesda, MD 20894 USA.
RP Feolo, M (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Informat Engn Branch, Bethesda, MD 20894 USA.
EM trykak@ncbi.nlm.nih.gov; hao@ncbi.nlm.nih.gov; feolo@ncbi.nlm.nih.gov
FU US National Institutes of Health, National Library of Medicine; National
Institutes of Health, National Library of Medicine
FX Intramural Research Program of the US National Institutes of Health,
National Library of Medicine. Funding for open access charge: Intramural
Research Program of the National Institutes of Health, National Library
of Medicine.
NR 2
TC 66
Z9 66
U1 2
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2014
VL 42
IS D1
BP D975
EP D979
DI 10.1093/nar/gkt1211
PG 5
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5LF
UT WOS:000331139800143
PM 24297256
ER
PT J
AU Wang, YL
Suzek, T
Zhang, J
Wang, JY
He, SQ
Cheng, TJ
Shoemaker, BA
Gindulyte, A
Bryant, SH
AF Wang, Yanli
Suzek, Tugba
Zhang, Jian
Wang, Jiyao
He, Siqian
Cheng, Tiejun
Shoemaker, Benjamin A.
Gindulyte, Asta
Bryant, Stephen H.
TI PubChem BioAssay: 2014 update
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID RNA INTERFERENCE SCREEN; SIGNALING PATHWAY; SMALL MOLECULES; REGULATORS;
DATABASE; GENES; CELLS
AB PubChem's BioAssay database (http://pubchem.ncbi.nlm.nih.gov) is a public repository for archiving biological tests of small molecules generated through high-throughput screening experiments, medicinal chemistry studies, chemical biology research and drug discovery programs. In addition, the BioAssay database contains data from high-throughput RNA interference screening aimed at identifying critical genes responsible for a biological process or disease condition. The mission of PubChem is to serve the community by providing free and easy access to all deposited data. To this end, PubChem BioAssay is integrated into the National Center for Biotechnology Information retrieval system, making them searchable by Entrez queries and cross-linked to other biomedical information archived at National Center for Biotechnology Information. Moreover, PubChem BioAssay provides web-based and programmatic tools allowing users to search, access and analyze bioassay test results and metadata. In this work, we provide an update for the PubChem BioAssay resource, such as information content growth, new developments supporting data integration and search, and the recently deployed PubChem Upload to streamline chemical structure and bioassay submissions.
C1 [Wang, Yanli; Suzek, Tugba; Zhang, Jian; Wang, Jiyao; He, Siqian; Cheng, Tiejun; Shoemaker, Benjamin A.; Gindulyte, Asta; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
RI Cheng, Tiejun/A-5344-2010; Suzek, Tugba/B-6943-2015;
OI Cheng, Tiejun/0000-0002-4486-3356; Suzek, Tugba/0000-0002-3243-1759
FU NIH; National Insitutes of Health, USA
FX The NIH Intramural Research program. Funding for open access charge:
National Insitutes of Health, USA.
NR 22
TC 94
Z9 95
U1 1
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2014
VL 42
IS D1
BP D1075
EP D1082
DI 10.1093/nar/gkt978
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5LF
UT WOS:000331139800158
PM 24198245
ER
PT J
AU Welter, D
MacArthur, J
Morales, J
Burdett, T
Hall, P
Junkins, H
Klemm, A
Flicek, P
Manolio, T
Hindorff, L
Parkinson, H
AF Welter, Danielle
MacArthur, Jacqueline
Morales, Joannella
Burdett, Tony
Hall, Peggy
Junkins, Heather
Klemm, Alan
Flicek, Paul
Manolio, Teri
Hindorff, Lucia
Parkinson, Helen
TI The NHGRI GWAS Catalog, a curated resource of SNP-trait associations
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SUSCEPTIBILITY LOCI; ONTOLOGY; DISEASE; INTEGRATION
AB The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies (GWAS) Catalog provides a publicly available manually curated collection of published GWAS assaying at least 100 000 single-nucleotide polymorphisms (SNPs) and all SNP-trait associations with P < 1 x 10(-5). The Catalog includes 1751 curated publications of 11 912 SNPs. In addition to the SNP-trait association data, the Catalog also publishes a quarterly diagram of all SNP-trait associations mapped to the SNPs' chromosomal locations. The Catalog can be accessed via a tabular web interface, via a dynamic visualization on the human karyotype, as a downloadable tab-delimited file and as an OWL knowledge base. This article presents a number of recent improvements to the Catalog, including novel ways for users to interact with the Catalog and changes to the curation infrastructure.
C1 [Welter, Danielle; MacArthur, Jacqueline; Morales, Joannella; Burdett, Tony; Flicek, Paul; Parkinson, Helen] European Bioinformat Inst, European Mol Biol Lab, Hinxton CB10 1SD, Cambs, England.
[Hall, Peggy; Junkins, Heather; Manolio, Teri; Hindorff, Lucia] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Klemm, Alan] NHGRI, Div Policy Commun & Educ, NIH, Bethesda, MD 20892 USA.
RP Parkinson, H (reprint author), European Bioinformat Inst, European Mol Biol Lab, Wellcome Trust Genome Campus, Hinxton CB10 1SD, Cambs, England.
EM hindorffl@mail.nih.gov; parkinson@ebi.ac.uk
OI Welter, Danielle/0000-0003-1058-2668; Burdett,
Anthony/0000-0002-2513-5396; Parkinson, Helen/0000-0003-3035-4195;
Flicek, Paul/0000-0002-3897-7955
FU National Institutes of Health [3U41-HG006104]; EMBL; Health Thematic
Area of the Cooperation Programme of the European Commission; NIH;
[200754]
FX The National Institutes of Health [3U41-HG006104 to D. W. and J.M-.A.]
and EMBL core funds supporting (to P. F., H. P. and T. B.); EMBL Core
Funds and by the Health Thematic Area of the Cooperation Programme of
the European Commission within the VII Framework Programme for Research
and Technological Development supported (to J.M.); Grant number [200754]
Gen2Phen. conducted this work as employees of the NHGRI, NIH (by H.A.J.,
P. H., K. A. H., T. A. M. and L. A. H.). Funding for open access charge:
NIH.
NR 20
TC 735
Z9 750
U1 7
U2 44
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD JAN
PY 2014
VL 42
IS D1
BP D1001
EP D1006
DI 10.1093/nar/gkt1229
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AA5LF
UT WOS:000331139800147
PM 24316577
ER
PT J
AU Kobayashi, H
Watanabe, R
Choyke, PL
AF Kobayashi, Hisataka
Watanabe, Rira
Choyke, Peter L.
TI Improving Conventional Enhanced Permeability and Retention (EPR)
Effects; What Is the Appropriate Target?
SO THERANOSTICS
LA English
DT Review
DE Cancer; Nano-delivery; Tumor physiology; Enhanced permeability and
retention effects
ID TRANSCAPILLARY PRESSURE-GRADIENT; HUMAN OSTEOSARCOMA XENOGRAFTS;
MACROMOLECULAR DRUG-DELIVERY; INTERSTITIAL FLUID PRESSURE; GROWTH-FACTOR
VEGF; TUMOR BLOOD-FLOW; SOLID TUMORS; LIPOSOMAL DOXORUBICIN;
VASCULAR-PERMEABILITY; PHARMACO-ANGIOGRAPHY
AB Nano-sized therapeutic agents have several advantages over low molecular weight agents such as a larger loading capacity, the ability to protect the payload until delivery, more specific targeting due to multivalency and the opportunity for controlled/sustained release. However, the delivery of nano-sized agents into cancer tissue is problematic because it mostly relies on the enhanced permeability and retention (EPR) effect that depends on the leaky nature of the tumor vasculature and the prolonged circulation of nano-sized agents, allowing slow but uneven accumulation in the tumor bed. Delivery of nano-sized agents is dependent on several factors that influence the EPR effect; 1. Regional blood flow to the tumor, 2. Permeability of the tumor vasculature, 3. Structural barriers imposed by perivascular tumor cells and extracellular matrix, 4. Intratumoral pressure. In this review, these factors will be described and methods to enhance nano-agent delivery will be reviewed.
C1 [Kobayashi, Hisataka; Watanabe, Rira; Choyke, Peter L.] NCI, Ctr Canc Res, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Ctr Canc Res, Mol Imaging Program, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA.
EM Kobayash@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 84
TC 141
Z9 146
U1 29
U2 139
PU IVYSPRING INT PUBL
PI LAKE HAVEN
PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
SN 1838-7640
J9 THERANOSTICS
JI Theranostics
PY 2014
VL 4
IS 1
BP 81
EP 89
DI 10.7150/thno.7193
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AA9GP
UT WOS:000331402100006
PM 24396516
ER
PT J
AU Kusumoto-Matsuo, R
Ghosh, D
Karmakar, P
May, A
Ramsden, D
Bohr, VA
AF Kusumoto-Matsuo, Rika
Ghosh, Deblina
Karmakar, Parimal
May, Alfred
Ramsden, Dale
Bohr, Vilhelm A.
TI Serines 440 and 467 in the Werner syndrome protein are phosphorylated by
DNA-PK and affects its dynamics in response to DNA double strand breaks
SO AGING-US
LA English
DT Article
DE Werner; WRN; DNA-PK; serine phosphorylation; DSB; etoposide
ID FUNCTIONAL INTERACTION; SYNDROME HELICASE; RECQ HELICASES; CATALYTIC
SUBUNIT; HUMAN-CELLS; IV COMPLEX; IN-VITRO; S-PHASE; KINASE; DAMAGE
AB WRN protein, defective in Werner syndrome (WS), a human segmental progeria, is a target of serine/threonine kinases involved in sensing DNA damage. DNA-PK phosphorylates WRN in response to DNA double strand breaks (DSBs). However, the main phosphorylation sites and functional importance of the phosphorylation of WRN has remained unclear. Here, we identify Ser-440 and -467 in WRN as major phosphorylation sites mediated by DNA-PK. In vitro, DNA-PK fails to phosphorylate a GST-WRN fragment with S440A and/or S467A substitution. In addition, full length WRN with the mutation expressed in 293T cells was not phosphorylated in response to DSBs produced by bleomycin. Accumulation of the mutant WRN at the site of laser-induced DSBs occurred with the same kinetics as wild type WRN in live HeLa cells. While the wild type WRN relocalized to the nucleoli after 24 hours recovery from etoposide-induced DSBs, the mutant WRN remained mostly in the nucleoplasm. Consistent with this, WS cells expressing the mutants exhibited less DNA repair efficiency and more sensitivity to etoposide, compared to those expressing wild type. Our findings indicate that phosphorylation of Ser-440 and -467 in WRN are important for relocalization of WRN to nucleoli, and that it is required for efficient DSB repair.
C1 [Kusumoto-Matsuo, Rika; May, Alfred; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Ghosh, Deblina; Karmakar, Parimal] Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, India.
[Ramsden, Dale] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Ramsden, Dale] Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
[Ramsden, Dale] Univ N Carolina, Chapel Hill, NC 27599 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU Postdoctoral Fellowship for Research Abroad of Japan Society for the
Promotion of Science (JSPS); Intramural Research Program of the National
Institutes of Health [CA84442]
FX This work was supported by the Postdoctoral Fellowship for Research
Abroad of Japan Society for the Promotion of Science (JSPS) [to R.K.];
and the Intramural Research Program of the National Institutes of Health
[CA84442 (to D.A.R)]. We thank Dr. Tomasz Kulikowicz for advice. We
thank Drs. M. Rossi and M. Raamamorthy for their critical reading of
this manuscript and Dr. T. Helleday for NU7026.
NR 43
TC 9
Z9 10
U1 1
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JAN
PY 2014
VL 6
IS 1
BP 70
EP 81
PG 12
WC Cell Biology
SC Cell Biology
GA AA0ZT
UT WOS:000330826600010
PM 24429382
ER
PT J
AU Chen, L
Mizutani, A
Kasai, T
Yan, T
Jin, GL
Vaidyanath, A
El-Aarag, BYA
Liu, YX
Kudoh, T
Salomon, DS
Fu, L
Seno, M
AF Chen, Ling
Mizutani, Akifumi
Kasai, Tomonari
Yan, Ting
Jin, Guoliang
Vaidyanath, Arun
El-Aarag, Bishoy Y. A.
Liu, Yixin
Kudoh, Takayuki
Salomon, David S.
Fu, Li
Seno, Masaharu
TI Mouse induced pluripotent stem cell microenvironment generates
epithelial-mesenchymal transition in mouse Lewis lung cancer cells
SO AMERICAN JOURNAL OF CANCER RESEARCH
LA English
DT Article
DE Mouse induced pluripotent stem cell; stem cell microenvironment;
epithelial-mesenchymal transition; lung Lewis cancer cell
ID TUMOR-CELLS; DISEASE; DIFFERENTIATION; METASTASIS; PHENOTYPE; GROWTH;
MODEL; LINE
AB Induced pluripotent stem (iPS) cells may be a powerful tool in regenerative medicine, but their potential tumorigenicity is a significant challenge for the clinical use of iPS cells. Previously, we succeeded in converting miPS cells into cancer stem cells (CSCs) under the conditions of tumor microenvironment. Both stem cells and tumor cells are profoundly influenced by bi-directional communication with their respective microenvironment, which dictates cell fate determination and behavior. The microenvironment derived from iPS cells has not been well studied. In this paper, we have investigated the effects of secreted factors from Nanog-mouse iPS (miPS) cells on mouse Lewis lung cancer (LLC) cells that are found in the conditioned media. The results demonstrated that miPS cells secrete factors that can convert the epithelia phenotype of LLC cells to a mesenchymal phenotype, and that can promote tumorigenisity, migration and invasion. Furthermore, LLC cells that have been exposed to miPS conditioned medium became resistant to apoptosis. These various biological effects suggest that the miPS microenvironment contain factors that can promote an epithelial-mesenchymal transition (EMT) through an active Snail-MMP axis or by suppressing differentiation in LLC cells.
C1 [Chen, Ling; Mizutani, Akifumi; Kasai, Tomonari; Yan, Ting; Jin, Guoliang; Vaidyanath, Arun; Kudoh, Takayuki; Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med & Bioengn Sci, Okayama 7008530, Japan.
[Chen, Ling] Tianjin Cent Hosp Gynecol Obstet, Dept Pathol, Tianjin 300100, Peoples R China.
[Chen, Ling; Liu, Yixin] Japan Soc Promot Sci, Tokyo 1028472, Japan.
[El-Aarag, Bishoy Y. A.] Menoufia Univ, Fac Sci, Dept Chem, Menoufia, Egypt.
[Salomon, David S.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
[Fu, Li] Tianjin Med Univ, Canc Hosp, Dept Breast Canc Pathol, Tianjin 300060, Peoples R China.
[Fu, Li] Tianjin Med Univ, Canc Hosp, Res Lab, State Key Lab Breast Canc Res, Tianjin 300060, Peoples R China.
RP Seno, M (reprint author), Okayama Univ, Grad Sch Nat Sci & Technol, Dept Med & Bioengn Sci, Kita Ku, 3-1-1 Tsushima Naka, Okayama 7008530, Japan.
EM fulijyb@hotmail.com; mseno@cc.okayama-u.ac.jp
RI SENO, Masaharu /B-2092-2011
OI SENO, Masaharu /0000-0001-8547-6259
FU Ministry of Education, Culture, Sports, Science and Technology in Japan
[21300179]
FX L. Chen was supported by Grant-in-Aid for JSPS Fellows. This work was
partly supported by Grant-in-Aid for Scientific Research (B) from the
Ministry of Education, Culture, Sports, Science and Technology (No.
21300179) in Japan.
NR 31
TC 5
Z9 5
U1 1
U2 15
PU E-CENTURY PUBLISHING CORP
PI MADISON
PA 40 WHITE OAKS LN, MADISON, WI 53711 USA
SN 2156-6976
J9 AM J CANCER RES
JI Am. J. Cancer Res.
PY 2014
VL 4
IS 1
BP 80
EP U92
PG 12
WC Oncology
SC Oncology
GA AA4MM
UT WOS:000331069800007
PM 24482741
ER
PT S
AU White, BH
Ewer, J
AF White, Benjamin H.
Ewer, John
BE Berenbaum, MR
TI Neural and Hormonal Control of Postecdysial Behaviors in Insects
SO ANNUAL REVIEW OF ENTOMOLOGY, VOL 59, 2014
SE Annual Review of Entomology
LA English
DT Review; Book Chapter
DE ecdysis; bursicon; wing expansion; Drosophila; neuroendocrine;
neuroethology
ID HAWKMOTH MANDUCA-SEXTA; IMAGINAL ECDYSIS; WING EXPANSION; NEURONAL
NETWORK; FRONTAL GANGLION; TELEOGRYLLUS-OCEANICUS; NEUROENDOCRINE
CONTROL; SCHISTOCERCA-GREGARIA; PEPTIDERGIC ENSEMBLES; DECISION NETWORK
AB The shedding of the old exoskeleton that occurs in insects at the end of a molt (a process called ecdysis) is typically followed by the expansion and tanning of a new one. At the adult molt, these postecdysial processes include expansion and hardening of the wings. Here we describe recent advances in understanding the neural and hormonal control of wing expansion and hardening, focusing on work using Drosophila melanogaster in which genetic manipulations have permitted detailed investigation of postecdysial processes and their modulation by sensory input. To place this work in context, we briefly review recent progress in understanding the neuroendocrine regulation of ecdysis, which appears to be largely conserved across insect species. Investigations into the neuroendocrine networks that regulate ecdysial and postecdysial behaviors provide insights into how stereotyped, yet environmentally responsive, sequences are generated and how they develop and evolve.
C1 [White, Benjamin H.] NIMH, Sect Neural Funct, Mol Biol Lab, Bethesda, MD 20892 USA.
[Ewer, John] Univ Valparaiso, Fac Ciencias, Ctr Interdisciplinario Neurociencia Valparaiso, Valparaiso, Chile.
RP White, BH (reprint author), NIMH, Sect Neural Funct, Mol Biol Lab, Bethesda, MD 20892 USA.
EM benjaminwhite@mail.nih.gov; john.ewer@uv.cl
OI Ewer, John/0000-0002-6806-3628
FU Intramural NIH HHS [, ZIA MH002800-10]; NIMH NIH HHS [ZIA MH002800]
NR 63
TC 11
Z9 11
U1 4
U2 28
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4170
BN 978-0-8243-0159-0
J9 ANNU REV ENTOMOL
JI Annu. Rev. Entomol.
PY 2014
VL 59
BP 363
EP 381
DI 10.1146/annurev-ento-011613-162028
PG 19
WC Entomology
SC Entomology
GA BJQ17
UT WOS:000329608900020
PM 24160420
ER
PT S
AU Burge, CA
Eakin, CM
Friedman, CS
Froelich, B
Hershberger, PK
Hofmann, EE
Petes, LE
Prager, KC
Weil, E
Willis, BL
Ford, SE
Harvell, CD
AF Burge, Colleen A.
Eakin, C. Mark
Friedman, Carolyn S.
Froelich, Brett
Hershberger, Paul K.
Hofmann, Eileen E.
Petes, Laura E.
Prager, Katherine C.
Weil, Ernesto
Willis, Bette L.
Ford, Susan E.
Harvell, C. Drew
BE Carlson, CA
Giovannoni, SJ
TI Climate Change Influences on Marine Infectious Diseases: Implications
for Management and Society
SO ANNUAL REVIEW OF MARINE SCIENCE, VOL 6
SE Annual Review of Marine Science
LA English
DT Review; Book Chapter
DE epizootics; mass mortalities; health; oceans; ocean warming
ID OYSTER CRASSOSTREA-VIRGINICA; ABALONE HALIOTIS-RUFESCENS;
HAPLOSPORIDIUM-NELSONI MSX; CANDIDATUS-XENOHALIOTIS-CALIFORNIENSIS;
DOLPHINS STENELLA-COERULEOALBA; RICKETTSIALES-LIKE PROKARYOTE; CARIBBEAN
ELKHORN CORAL; SEA-SURFACE TEMPERATURE; BLACK BAND DISEASE;
GREAT-BARRIER-REEF
AB Infectious diseases are common in marine environments, but the effects of a changing climate on marine pathogens are not well understood. Here we review current knowledge about how the climate drives host-pathogen interactions and infectious disease outbreaks. Climate-related impacts on marine diseases are being documented in corals, shellfish, finfish, and humans; these impacts are less clearly linked for other organisms. Oceans and people are inextricably linked, and marine diseases can both directly and indirectly affect human health, livelihoods, and well-being. We recommend an adaptive management approach to better increase the resilience of ocean systems vulnerable to marine diseases in a changing climate. Land-based management methods of quarantining, culling, and vaccinating are not successful in the ocean; therefore, forecasting conditions that lead to outbreaks and designing tools/approaches to influence these conditions may be the best way to manage marine disease.
C1 [Burge, Colleen A.; Harvell, C. Drew] Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
[Eakin, C. Mark] NOAA, Coral Reef Watch, College Pk, MD 20740 USA.
[Friedman, Carolyn S.] Univ Washington, Sch Aquat & Fishery Sci, Seattle, WA 98195 USA.
[Froelich, Brett] Univ N Carolina, Inst Marine Sci, Morehead City, NC 28557 USA.
[Hershberger, Paul K.] US Geol Survey, Marrowstone Marine Field Stn, Western Fisheries Res Ctr, Nordland, WA 98358 USA.
[Hofmann, Eileen E.] Old Dominion Univ, Dept Ocean Earth & Atmospher Sci, Ctr Coastal Phys Oceanog, Norfolk, VA 23508 USA.
[Petes, Laura E.] NOAA, Climate Program Off, Silver Spring, MD 20910 USA.
[Prager, Katherine C.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Prager, Katherine C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Weil, Ernesto] Univ Puerto Rico, Dept Marine Sci, Mayaguez, PR 00680 USA.
[Willis, Bette L.] James Cook Univ, Australian Res Council Ctr Excellence Coral Reef, Townsville, Qld 4811, Australia.
[Willis, Bette L.] James Cook Univ, Sch Marine & Trop Biol, Townsville, Qld 4811, Australia.
[Ford, Susan E.] Rutgers State Univ, Haskin Shellfish Res Lab, Port Norris, NJ 08349 USA.
RP Burge, CA (reprint author), Cornell Univ, Dept Ecol & Evolutionary Biol, Ithaca, NY 14853 USA.
EM cab433@cornell.edu; mark.eakin@noaa.gov; carolynf@uw.edu;
bafroeli@unc.edu; phershberger@usgs.gov; hofmann@ccpo.odu.edu;
laura.petes@noaa.gov; kcprager@ucla.edu; reefpal@gmail.com;
bette.willis@jcu.edu.au; susan@hsrl.rutgers.edu; cdh5@cornell.edu
RI Eakin, C. Mark/F-5585-2010
NR 198
TC 83
Z9 87
U1 25
U2 214
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 1941-1405
BN 978-0-8243-4506-8
J9 ANNU REV MAR SCI
JI Annu. Rev. Mar. Sci.
PY 2014
VL 6
BP 249
EP 277
DI 10.1146/annurev-marine-010213-135029
PG 29
WC Geochemistry & Geophysics; Marine & Freshwater Biology; Oceanography
SC Geochemistry & Geophysics; Marine & Freshwater Biology; Oceanography
GA BJQ32
UT WOS:000329657800012
PM 23808894
ER
PT S
AU Niciu, MJ
Henter, ID
Luckenbaugh, DA
Zarate, CA
Charney, DS
AF Niciu, Mark J.
Henter, Ioline D.
Luckenbaugh, David A.
Zarate, Carlos A., Jr.
Charney, Dennis S.
BE Insel, PA
TI Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives
for the Treatment of Depression: Ketamine and Other Compounds
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 54
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE NMDA receptor antagonist; rapid-acting antidepressants; major depressive
disorder; bipolar depression; preclinical models of depression;
mammalian target of rapamycin; mTOR
ID TREATMENT-RESISTANT DEPRESSION; D-ASPARTATE ANTAGONIST; RAPID
ANTIDEPRESSANT RESPONSE; CLUB-DRUG-USE; MAGNETIC-RESONANCE-SPECTROSCOPY;
NEW-YORK-CITY; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED
CONTROLLED-TRIAL; DELTA-SLEEP RATIO; LOW-DOSE KETAMINE
AB The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression. These effects are in direct contrast to the more modest effects seen after weeks of treatment with classic monoaminergic antidepressants. Numerous open-label and case studies similarly validate ketamine's antidepressant properties. These clinical findings have been reverse-translated into preclinical models in an effort to elucidate ketamine's antidepressant mechanism of action, and three important targets have been identified: mammalian target of rapamycin (mTOR), eukaryotic elongation factor 2 (eEF2), and glycogen synthase kinase-3 (GSK-3). Current clinical and preclinical research is focused on (a) prolonging/maintaining ketamine's antidepressant effects, (b) developing more selective NMDA receptor antagonists free of ketamine's adverse effects, and (c) identifying predictor, mediator/moderator, and treatment response biomarkers of ketamine's antidepressant effects.
C1 [Niciu, Mark J.; Henter, Ioline D.; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20814 USA.
[Charney, Dennis S.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
RP Niciu, MJ (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20814 USA.
EM mark.niciu@nih.gov
RI Niciu, Mark/J-1766-2014
OI Niciu, Mark/0000-0002-5612-3021
FU Intramural NIH HHS [ZIA MH002857-09]
NR 132
TC 44
Z9 45
U1 5
U2 41
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0454-6
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2014
VL 54
BP 119
EP 139
DI 10.1146/annurev-pharmtox-011613-135950
PG 21
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BJR57
UT WOS:000329822200007
PM 24392693
ER
PT J
AU Xavier, CP
Melikova, M
Chuman, Y
Uren, A
Baljinnyam, B
Rubin, JS
AF Xavier, Charles P.
Melikova, Maria
Chuman, Yoshiro
Ueren, Aykut
Baljinnyam, Bolormaa
Rubin, Jeffrey S.
TI Secreted Frizzled-related protein potentiation versus inhibition of
Wnt3a/beta-catenin signaling
SO CELLULAR SIGNALLING
LA English
DT Article
DE beta-Catenin; Cysteine-rich domain; Frizzled; sFRP; Wnt
ID RENAL-CELL CARCINOMA; WNT/BETA-CATENIN; WNT ANTAGONIST;
MYOCARDIAL-INFARCTION; COLORECTAL-CANCER; SPEMANN ORGANIZER;
PROSTATE-CANCER; BETA-CATENIN; SFRP1; RECEPTOR
AB Wnt signaling regulates a variety of cellular processes during embryonic development and in the adult. Many of these activities are mediated by the Frizzled family of seven-pass transmembrane receptors, which bind Wnts via a conserved cysteine-rich domain (CRD). Secreted Frizzled-related proteins (sFRPs) contain an amino-terminal, Frizzled-like CRD and a carboxyl-terminal, heparin-binding netrin-like domain. Previous studies identified sFRPs as soluble Wnt antagonists that bind directly to Wnts and prevent their interaction with Frizzleds. However, subsequent observations suggested that sFRPs and Frizzleds form homodimers and heterodimers via their respective CRDs, and that sFRPs can stimulate signal transduction. Here, we present evidence that sFRP1 either inhibits or enhances signaling in the Wnt3a/beta-catenin pathway, depending on its concentration and the cellular context. Nanomolar concentrations of sFRP1 increased Wnt3a signaling, while higher concentrations blocked it in HEK293 cells expressing a SuperTopFlash reporter. sFRP1 primarily augmented Wnt3a/beta-catenin signaling in C57MG cells, but it behaved as an antagonist in L929 fibroblasts. sFRP1 enhanced reporter activity in L cells that were engineered to stably express Frizzled 5, though not Frizzled 2. This implied that the Frizzled expression pattern could determine the response to sFRP1. Similar results were obtained with sFRP2 in HEK293, C57MG and L cell reporter assays. CRDsFRP1 mimicked the potentiating effect of sFRP1 in multiple settings, contradicting initial expectations that this domain would inhibit Wnt signaling. Moreover, CRDsFRP1 showed little avidity for Wnt3a compared to sFRP1, implying that the mechanism for potentiation by CRDsFRP1 probably does not require an interaction with Wnt protein. Together, these findings demonstrate that sFRPs can either promote or suppress Wnt/beta-catenin signaling, depending on cellular context, concentration and most likely the expression pattern of Fzd receptors. Published by Elsevier Inc.
C1 [Xavier, Charles P.; Melikova, Maria; Chuman, Yoshiro; Baljinnyam, Bolormaa; Rubin, Jeffrey S.] Natl Canc Inst, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA.
[Ueren, Aykut] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
RP Rubin, JS (reprint author), Bldg 37,Room 2042,37 Convent Dr,MSC 4256, Bethesda, MD 20892 USA.
EM rubinj@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX We thank Drs. Xi He, Ray Habas and Randall Moon for providing us with
plasmids, and Dr. Jeremy Nathans for sharing the HEK293/STF cell line.
We also appreciate discussions with Dr. Sarangan Ravichandran
(SAIC-Frederick, Inc.) about CRDsFRP1 and input from other
members of the Rubin lab including Dr. Yoshimi Greer and Saad Saffo.
This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 56
TC 20
Z9 20
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
EI 1873-3913
J9 CELL SIGNAL
JI Cell. Signal.
PD JAN
PY 2014
VL 26
IS 1
BP 94
EP 101
DI 10.1016/j.cellsig.2013.09.016
PG 8
WC Cell Biology
SC Cell Biology
GA AA0WH
UT WOS:000330817600010
PM 24080158
ER
PT J
AU Nguyen, AB
Clark, TT
Belgrave, FZ
AF Nguyen, Anh B.
Clark, Trenette T.
Belgrave, Faye Z.
TI Gender Roles and Acculturation: Relationships With Cancer Screening
Among Vietnamese American Women
SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY
LA English
DT Article
DE Vietnamese American; women; breast cancer; cervical cancer;
self-efficacy
ID ASIAN-AMERICAN; BREAST-CANCER; UNITED-STATES; BEHAVIORAL-MODEL; ROLE
TRAITS; HEALTH; ATTITUDES; CARE; PREDICTORS; SEX
AB The aim of this study was to examine the influence of demographic variables and the interplay between gender roles and acculturation on breast and cervical cancer screening outcomes among Vietnamese American women. Convenience sampling was used to recruit 100 Vietnamese women from the Richmond, VA, metropolitan area. Women were recruited to participate in a larger cancer screening intervention. All participants completed measures on demographic variables, gender roles, acculturation, and cancer screening variables. Findings indicated that traditional masculine gender roles were associated with increased self-efficacy for breast and cervical cancer screening. Higher levels of acculturation were associated with higher probability of having had a Papanicolaou test. In addition, acculturation moderated the relationship between traditional female gender roles and cancer screening variables. For highly acculturated women, higher levels of feminine gender roles predicted higher probability of having had a previous clinical breast exam and higher levels of self-efficacy for cervical cancer screening, while the opposite was true for lower acculturated women. The findings of this study indicate the important roles that sociodemographic variables, gender roles, and acculturation play in affecting health attitudes and behaviors among Vietnamese women. These findings also help to identify a potentially high-risk subgroup and existing gaps that need to be targeted by preventive interventions.
C1 [Nguyen, Anh B.] NCI, Canc Prevent Fellowship Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Clark, Trenette T.] Univ N Carolina, Sch Social Work, Chapel Hill, NC USA.
[Belgrave, Faye Z.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA.
RP Nguyen, AB (reprint author), NCI, Canc Prevent Fellowship Program, Rockville, MD 20850 USA.
EM anh.nguyen3@nih.gov
FU NCI NIH HHS [5F31CA136235]; NIDA NIH HHS [K01 DA035895]
NR 59
TC 2
Z9 2
U1 0
U2 0
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1099-9809
EI 1939-0106
J9 CULT DIVERS ETHN MIN
JI Cult. Divers. Ethn. Minor. Psychol.
PD JAN
PY 2014
VL 20
IS 1
BP 87
EP 97
DI 10.1037/a0033474
PG 11
WC Ethnic Studies; Psychology, Social
SC Ethnic Studies; Psychology
GA AA1SN
UT WOS:000330876100011
PM 24491129
ER
PT S
AU Wall, VE
Garvey, LA
Mehalko, JL
Procter, LV
Esposito, D
AF Wall, Vanessa E.
Garvey, Leslie A.
Mehalko, Jennifer L.
Procter, Lauren V.
Esposito, Dominic
BE Valla, S
Lale, R
TI Combinatorial Assembly of Clone Libraries Using Site-Specific
Recombination
SO DNA CLONING AND ASSEMBLY METHODS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Cloning; Gateway; Site-specific recombination; Combinatorics
ID PROTEIN EXPRESSION; MAMMALIAN-CELLS; DNA CLONING; GENES
AB Generation of DNA clones for use in proteomic and genomic research often requires a significant level of parallel production, as the number of downstream options for these experiments increases. Where a single fluorescently tagged construct may have sufficed before, there is now the need for multiple types of labels for different readouts and different assays. Protein expression, which once utilized a very small set of vectors because of low throughput expression and purification, has now rapidly matured into a high throughput system in which dozens of conditions can be tested in parallel to identify the best candidate clones. This has returned the bottleneck in many of these technologies to the generation of DNA clones, and standard cloning techniques often dramatically limit the throughput and success of such processes. In order to overcome this bottleneck, higher-throughput and more parallel cloning processes need to be developed which would allow rapid, inexpensive production of final clones. In addition, there is a strong need to utilize standardized elements to avoid unnecessarily remaking fragments of clones that could be used in multiple constructs.
The advent of recombinational cloning helped to increase the parallel processing of DNA clones, but was still limited by the need to generate different vector backbones for each specific need. The solution to this problem emerged with the introduction of combinatorial approaches to clone construction, based on either homologous or site-specific recombination processes. In particular, the Gateway Multisite system provides all of the necessary components for a highly parallel, inexpensive, rapid, and diverse platform for clone construction in many areas of proteomic and genomic research. Here we describe our optimized system for combinatorial cloning, including improvements in cloning protocols and construct design that permit users to easily generate libraries of clones which can be combined in parallel to create an unlimited number of final constructs. The system is capable of utilizing the tens of thousands of commercially available Gateway clones already in existence, and allows easy adaptation of most DNA vectors to the system.
C1 [Wall, Vanessa E.; Garvey, Leslie A.; Mehalko, Jennifer L.; Procter, Lauren V.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Prot Express Lab, Frederick, MD 21702 USA.
[Esposito, Dominic] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Wall, VE (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Prot Express Lab, Frederick, MD 21702 USA.
FU PHS HHS [HHSN261200800001E]
NR 9
TC 1
Z9 1
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 978-1-62703-763-1; 978-1-62703-764-8
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1116
BP 193
EP 208
DI 10.1007/978-1-62703-764-8_14
D2 10.1007/978-1-62703-764-8
PG 16
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BJR28
UT WOS:000329761800015
PM 24395366
ER
PT J
AU Quick, VM
Byrd-Bredbenner, C
AF Quick, Virginia M.
Byrd-Bredbenner, Carol
TI Disordered eating, socio-cultural media influencers, body image, and
psychological factors among a racially/ethnically diverse population of
college women
SO EATING BEHAVIORS
LA English
DT Article
DE Disordered eating; Body image; Women; College
ID UNIVERSITY-STUDENTS; DEPRESSIVE SYMPTOMS; ADOLESCENT GIRLS; COMMUNITY
SAMPLE; AFRICAN-AMERICAN; DISSATISFACTION; WEIGHT; BLACK; BEHAVIORS;
FEMALES
AB This study examined disordered eating, socio-cultural media influencers, body image, and psychological factors among a large, racially/ethnically diverse sample of college women (n = 1445; 58% White, 21% Asian, 11% Hispanic, 11% Black) who completed an online survey. Black women were significantly more satisfied with their weight and shape and had lower eating concerns, disinhibited eating, and emotional eating than all other racial/ethnic groups. Black women tended to have significantly higher levels of self-esteem, were less likely to compare their body to those of people in the media, felt less pressured to attain the physical appearance standard set by the media, and had less awareness of the societal appearance norms set by the media than other racial groups. Findings suggest that Black college women, independent of weight status, may be protected from disordered eating, negative body image, and societal media pressures. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Quick, Virginia M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, DHHS, Bethesda, MD 20892 USA.
[Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA.
RP Quick, VM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, DHHS, Bethesda, MD 20892 USA.
EM gingermquick@gmail.com; bredbenner@aesop.rutgers.edu
RI Byrd-Bredbenner, Carol/F-8064-2015;
OI Byrd-Bredbenner, Carol/0000-0002-8010-3987; Quick,
Virginia/0000-0002-4338-963X
FU Intramural NIH HHS [Z99 HD999999]
NR 39
TC 11
Z9 12
U1 3
U2 38
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1471-0153
EI 1873-7358
J9 EAT BEHAV
JI Eat. Behav.
PD JAN
PY 2014
VL 15
IS 1
BP 37
EP 41
DI 10.1016/j.eatbeh.2013.10.005
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AA3WM
UT WOS:000331025900008
PM 24411747
ER
PT J
AU Aggleton, JP
Saunders, RC
Wright, NF
Vann, SD
AF Aggleton, John P.
Saunders, Richard C.
Wright, Nicholas F.
Vann, Seralynne D.
TI The origin of projections from the posterior cingulate and retrosplenial
cortices to the anterior, medial dorsal and laterodorsal thalamic nuclei
of macaque monkeys
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cingulate cortex; memory; primate; retrosplenial cortex; thalamus
ID MILD COGNITIVE IMPAIRMENT; HEAD-DIRECTION CELLS; ALZHEIMERS-DISEASE;
RHESUS-MONKEY; EFFERENT PROJECTIONS; MEDIODORSAL NUCLEUS; CORTEX; RAT;
CONNECTIONS; LESIONS
AB Interactions between the posterior cingulate cortex (areas 23 and 31) and the retrosplenial cortex (areas 29 and 30) with the anterior, laterodorsal and dorsal medial thalamic nuclei are thought to support various aspects of cognition, including memory and spatial processing. To detail these interactions better, the present study used retrograde tracers to reveal the origins of the corticothalamic projections in two closely related monkey species (Macaca mulatta, Macaca fascicularis). The medial dorsal thalamic nucleus received only light cortical inputs, which predominantly arose from area 23. Efferents to the anterior medial thalamic nucleus also arose principally from area 23, but these projections proved more numerous than those to the medial dorsal nucleus and also involved additional inputs from areas 29 and 30. The anterior ventral and laterodorsal thalamic nuclei had similar sources of inputs from the posterior cingulate and retrosplenial cortices. For both nuclei, the densest projections arose from areas 29 and 30, with numbers of thalamic inputs often decreasing when going dorsal from area 23a to 23c and to area 31. In all cases, the corticothalamic projections almost always arose from the deepest cortical layer. The different profiles of inputs to the anterior medial and anterior ventral thalamic nuclei reinforce other anatomical and electrophysiological findings suggesting that these adjacent thalamic nuclei serve different, but complementary, functions supporting memory. While the lack of retrosplenial connections singled out the medial dorsal nucleus, the very similar connection patterns shown by the anterior ventral and laterodorsal nuclei point to common roles in cognition.
C1 [Aggleton, John P.; Wright, Nicholas F.; Vann, Seralynne D.] Cardiff Univ, Sch Psychol, Cardiff CF10 3AT, S Glam, Wales.
[Saunders, Richard C.] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, 70 Pk Pl, Cardiff CF10 3AT, S Glam, Wales.
EM Aggleton@cf.ac.uk
OI Vann, Seralynne/0000-0002-6709-8773; Aggleton, John/0000-0002-5573-1308
FU Wolfson Research Merit Award
FX This research received support from a Wolfson Research Merit Award.
NR 77
TC 5
Z9 5
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD JAN
PY 2014
VL 39
IS 1
BP 107
EP 123
DI 10.1111/ejn.12389
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA AA3DI
UT WOS:000330972700011
PM 24134130
ER
PT J
AU Mansky, PJ
Wallerstedt, DB
Sannes, TS
Stagl, J
Johnson, LL
Blackman, MR
Grem, JL
Swain, SM
Monahan, BP
AF Mansky, Patrick J.
Wallerstedt, Dawn B.
Sannes, Timothy S.
Stagl, Jamie
Johnson, Laura Lee
Blackman, Marc R.
Grem, Jean L.
Swain, Sandra M.
Monahan, Brian P.
TI NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients
with Advanced Solid Tumors (vol 2013, 964592, 2013)
SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Correction
C1 [Mansky, Patrick J.] Bellin Hlth, Canc Team, Green Bay, WI 54313 USA.
[Mansky, Patrick J.; Johnson, Laura Lee] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Wallerstedt, Dawn B.] Samueli Inst, Alexandria, VA 22314 USA.
[Sannes, Timothy S.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA.
[Stagl, Jamie] Univ Miami, Miami, FL 33124 USA.
[Blackman, Marc R.] Georgetown Univ, Sch Med, Vet Affairs Med Ctr, Res Serv 151, Washington, DC 20422 USA.
[Blackman, Marc R.] Georgetown Univ, Sch Med, Dept Med, Washington, DC 20422 USA.
[Grem, Jean L.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
[Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
[Monahan, Brian P.] Uniformed Serv Univ Hlth Sci, Dept Med, Hematol & Med Oncol Div, Bethesda, MD 20814 USA.
RP Mansky, PJ (reprint author), Bellin Hlth, Canc Team, 1580 Commanche Ave, Green Bay, WI 54313 USA.
EM manpaj@bellin.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 1741-427X
EI 1741-4288
J9 EVID-BASED COMPL ALT
JI Evid.-based Complement Altern. Med.
PY 2014
AR 606348
DI 10.1155/2014/606348
PG 2
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA AB4MX
UT WOS:000331765100001
ER
PT J
AU Talavage, TM
Gonzalez-Castillo, J
Scott, SK
AF Talavage, Thomas M.
Gonzalez-Castillo, Javier
Scott, Sophie K.
TI Auditory neuroimaging with fMRI and PET
SO HEARING RESEARCH
LA English
DT Review
ID COCHLEAR IMPLANT PATIENTS; SCANNER ACOUSTIC NOISE; CEREBRAL-BLOOD-FLOW;
HUMAN VISUAL-CORTEX; TONOTOPIC ORGANIZATION; FUNCTIONAL MRI; HUMAN
BRAIN; NEURONAL-ACTIVITY; SENSORY STIMULATION; SPEECH-PERCEPTION
AB For much of the past 30 years, investigations of auditory perception and language have been enhanced or even driven by the use of functional neuroimaging techniques that specialize in localization of central responses. Beginning with investigations using positron emission tomography (PET) and gradually shifting primarily to usage of functional magnetic resonance imaging (fMRI), auditory neuroimaging has greatly advanced our understanding of the organization and response properties of brain regions critical to the perception of and communication with the acoustic world in which we live. As the complexity of the questions being addressed has increased, the techniques, experiments and analyses applied have also become more nuanced and specialized. A brief review of the history of these investigations sets the stage for an overview and analysis of how these neuroimaging modalities are becoming ever more effective tools for understanding the auditory brain. We conclude with a brief discussion of open methodological issues as well as potential clinical applications for auditory neuroimaging.
This article is part of a Special Issue entitled . (C) 2013 Elsevier B.V. All rights reserved.
C1 [Talavage, Thomas M.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA.
[Talavage, Thomas M.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA.
[Gonzalez-Castillo, Javier] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Scott, Sophie K.] UCL, Inst Cognit Neurosci, London, England.
RP Talavage, TM (reprint author), 465 Northwestern Ave, W Lafayette, IN 47907 USA.
EM tmt@purdue.edu
RI Scott, Sophie/A-1843-2010;
OI Scott, Sophie/0000-0001-7510-6297; Gonzalez-Castillo,
Javier/0000-0002-6520-5125
FU NIBIB NIH HHS [R01 EB003990]; Wellcome Trust [090961]
NR 155
TC 12
Z9 12
U1 4
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
EI 1878-5891
J9 HEARING RES
JI Hear. Res.
PD JAN
PY 2014
VL 307
SI SI
BP 4
EP 15
DI 10.1016/j.heares.2013.09.009
PG 12
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA AA8LU
UT WOS:000331347800002
PM 24076424
ER
PT J
AU Parrish, JA
Schachter, SC
Carleton, PF
Dempsey, M
Spiliotis, D
Collins, J
AF Parrish, John A.
Schachter, Steven C.
Carleton, Penny Ford
Dempsey, Mike
Spiliotis, Diane
Collins, John
TI Accelerating the Innovation Cycle
SO IEEE PULSE
LA English
DT Article
C1 [Parrish, John A.; Schachter, Steven C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Schachter, Steven C.; Spiliotis, Diane; Collins, John] CIMIT, Boston, MA USA.
[Carleton, Penny Ford] NIBIB Point Of Care Technol Ctr Primary Care, CIMITs Clin Syst Innovat Program, Bethesda, MD USA.
[Carleton, Penny Ford] CIMIT, Boston Simulat Consortium, Boston, MA USA.
[Dempsey, Mike] CIMIT, Accelerator Program, Boston, MA USA.
RP Parrish, JA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
EM jparrish@partners.org; sschacht@bidmc.harvard.edu;
pcarleton@partners.org; mdempsey1@partners.org; dspiliotis@partners.org;
Jcollins11@partners.org
NR 0
TC 1
Z9 1
U1 0
U2 3
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD JAN-FEB
PY 2014
VL 5
IS 1
BP 46
EP 54
DI 10.1109/MPUL.2013.2289464
PG 9
WC Engineering, Biomedical
SC Engineering
GA AA2AU
UT WOS:000330898300010
PM 25296373
ER
PT J
AU Tugarinov, V
Venditti, V
Clore, GM
AF Tugarinov, Vitali
Venditti, Vincenzo
Clore, G. Marius
TI A NMR experiment for simultaneous correlations of valine and
leucine/isoleucine methyls with carbonyl chemical shifts in proteins
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Chemical shift assignments; Methyl labeling; Enzyme I; Methyl TROSY;
Isotope shifts
ID MOLECULAR-WEIGHT PROTEINS; BACTERIAL PHOSPHOTRANSFERASE SYSTEM; COLI
ENZYME-I; SUGAR-TRANSPORT; TERMINAL DOMAIN; MONOMER/DIMER TRANSITION;
SALMONELLA-TYPHIMURIUM; MULTIDIMENSIONAL NMR; LABELING STRATEGY;
SPECTROSCOPY
AB A methyl-detected 'out-and-back' NMR experiment for obtaining simultaneous correlations of methyl resonances of valine and isoleucine/leucine residues with backbone carbonyl chemical shifts, SIM-HMCM(CGCBCA)CO, is described. The developed pulse-scheme serves the purpose of convenience in recording a single data set for all Ile(delta 1), Leu(delta) and Val(gamma) (ILV) methyl positions instead of acquiring two separate spectra selective for valine or leucine/isoleucine residues. The SIM-HMCM(CGCBCA)CO experiment can be used for ILV methyl assignments in moderately sized protein systems (up to similar to 100 kDa) where the backbone chemical shifts of C-13(alpha), C-13(beta) and (CO)-C-13 are known from prior NMR studies and where some losses in sensitivity can be tolerated for the sake of an overall reduction in NMR acquisition time.
C1 [Tugarinov, Vitali; Venditti, Vincenzo; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tugarinov, V (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM vitali.tugarinov@nih.gov; mariusc@intra.niddk.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU Intramural Program of the NIH; NIDDK; Intramural AIDS Targeted Antiviral
Program of the Office of the Director of the NIH
FX This work was supported by funds from the Intramural Program of the NIH,
NIDDK, and the Intramural AIDS Targeted Antiviral Program of the Office
of the Director of the NIH (to G. M. C.).
NR 59
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U1 2
U2 18
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
EI 1573-5001
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD JAN
PY 2014
VL 58
IS 1
BP 1
EP 8
DI 10.1007/s10858-013-9803-1
PG 8
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA AA1AA
UT WOS:000330827300001
PM 24346684
ER
PT J
AU Huang, RSP
Oleske, DA
Tholpady, A
Chang, BN
Dasgupta, A
Nguyen, A
Wahed, A
AF Huang, Richard Sheng Poe
Oleske, Deanna Alicia
Tholpady, Ashok
Chang, Brian N.
Dasgupta, Amitava
Andy Nguyen
Wahed, Amer
TI High False-Positive Rate for Monoclonal Gammopathy Using Capillary
Electrophoresis (CAPILLARYS 2) Alone
SO JOURNAL OF CLINICAL LABORATORY ANALYSIS
LA English
DT Article
DE monoclonal gammopathy; capillary zone electrophoresis; agarose gel
electrophoresis; immunofixation electrophoresis
ID SERUM-PROTEIN ELECTROPHORESIS; AGAROSE-GEL ELECTROPHORESIS;
ZONE-ELECTROPHORESIS; PARAPROTEINS; PERFORMANCE; SEPARATION; SYSTEM;
SEBIA
AB BackgroundCapillary zone electrophoresis (CZE) is a newer method of performing serum protein electrophoresis and is considered to be faster and more efficient than agarose gel method. We decided to evaluate CZE as an efficient screening tool for monoclonal gammopathies, and we began recommending immunofixation studies in cases with such minor/subtle distortions to avoid missing monoclonal gammopathies.
MethodsWe evaluated 163 serum protein agarose gel electrophoresis (SPAGE) samples between October and November 2011, and 447 serum protein CZE (SPCZE) samples between January 2012 to February 2012 and August 2012 to September 2012.
ResultsImmunofixation studies were recommended in 51 of 163 cases (31.3%) performed by SPAGE, and in 274 of 447 cases (61.3%) performed by SPCZE. While using SPAGE, of the 51 cases recommended for immunofixation (24 were performed to date), six cases (25.0%) were positive for monoclonal gammopathy. In contrast, while using SPCZE, of the 274 cases recommended for immunofixation (118 were performed to date), 18 cases (15.2%) were positive for monoclonal gammopathy. Using the SPCZE method, of these 18 cases, five (27.8%) had minor/subtle distortions without obvious peaks. Our recommendation rate for immunofixation studies has thus almost doubled (61.3% vs. 31.3%) with the adoption of SPCZE. Yet, using SPCZE has not translated to detecting more cases of true monoclonal gammopathies.
ConclusionTherefore, we conclude that there is a high false-positive rate for monoclonal gammopathy using CE alone. (C) 2013 Wiley Periodicals, Inc.
C1 [Huang, Richard Sheng Poe; Oleske, Deanna Alicia; Chang, Brian N.; Dasgupta, Amitava; Andy Nguyen; Wahed, Amer] Univ Texas Hlth Sci Ctr Houston, Dept Pathol & Lab Med, Houston, TX 77030 USA.
[Tholpady, Ashok] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Wahed, A (reprint author), Univ Texas Hlth Sci Ctr Houston, 6431 Fannin St,MSB 2-278, Houston, TX 77030 USA.
EM Md.A.Wahed@uth.tmc.edu
OI Tholpady, Ashok/0000-0003-3978-9574
NR 17
TC 1
Z9 1
U1 0
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-8013
EI 1098-2825
J9 J CLIN LAB ANAL
JI J. Clin. Lab. Anal.
PD JAN
PY 2014
VL 28
IS 1
BP 42
EP 46
DI 10.1002/jcla.21641
PG 5
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA AA0OF
UT WOS:000330793800007
PM 24375896
ER
PT J
AU Baranowski, T
Islam, N
Douglass, D
Dadabhoy, H
Beltran, A
Baranowski, J
Thompson, D
Cullen, KW
Subar, AF
AF Baranowski, T.
Islam, N.
Douglass, D.
Dadabhoy, H.
Beltran, A.
Baranowski, J.
Thompson, D.
Cullen, K. W.
Subar, A. F.
TI Food Intake Recording Software System, version 4 (FIRSSt4): a
self-completed 24-h dietary recall for children
SO JOURNAL OF HUMAN NUTRITION AND DIETETICS
LA English
DT Review
DE assessment; children; diet; recall; web-based
ID 13-YEAR-OLD CHILDREN; MEASUREMENT ERROR; ACCURACY; RELIABILITY;
4TH-GRADE; VALIDITY; STUDENTS
AB The Food Intake Recording Software System, version 4 (firsst4), is a web-based 24-h dietary recall (24hdr) self-administered by children based on the Automated Self-Administered 24-h recall (ASA24) (a self-administered 24hdr for adults). The food choices in firsst4 are abbreviated to include only those reported by children in US national surveys; and detailed food probe questions are simplified to exclude those that children could not be expected to answer (e.g. questions regarding food preparation and added fats). ASA24 and firsst4 incorporate 10000+ food images, with up to eight images per food, to assist in portion size estimation. We review the formative research conducted during the development of firsst4. When completed, firsst4 will be hosted and maintained for investigator use on the National Cancer Institute's ASA24 website.
C1 [Baranowski, T.; Islam, N.; Douglass, D.; Dadabhoy, H.; Beltran, A.; Baranowski, J.; Thompson, D.; Cullen, K. W.] USDA ARS, Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
[Subar, A. F.] Natl Canc Inst, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch EPN 4005, Bethesda, MD USA.
RP Baranowski, T (reprint author), USDA ARS, Baylor Coll Med, Childrens Nutr Res Ctr, 1100 Bates St, Houston, TX 77030 USA.
EM tbaranow@bcm.edu
OI Baranowski, Tom/0000-0002-0653-2222
FU National Cancer Institute [5 U01 CA130762-02]; USDA/ARS [58-6250-6001]
FX The authors declare that they have no conflicts of interest. This
research was primarily funded by a grant from the National Cancer
Institute (5 U01 CA130762-02). This work is also a publication of the
United States Department of Agriculture (USDA/ARS) Children's Nutrition
Research Center, Department of Pediatrics, Baylor College of Medicine,
Houston, Texas, and had been funded in part with federal funds from the
USDA/ARS under Cooperative Agreement No. 58-6250-6001. The contents of
this publication do not necessarily reflect the views or policies of the
USDA, nor does mention of trade names, commercial products, or
organisations imply endorsement from the US government.
NR 34
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U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3871
EI 1365-277X
J9 J HUM NUTR DIET
JI J. Hum. Nutr. Diet.
PD JAN
PY 2014
VL 27
SU 1
SI SI
BP 66
EP 71
DI 10.1111/j.1365-277X.2012.01251.x
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AA5JH
UT WOS:000331131400009
PM 22616645
ER
PT J
AU Wei, L
Shi, JF
Afari, G
Bhattacharyya, S
AF Wei, Ling
Shi, Jianfeng
Afari, George
Bhattacharyya, Sibaprasad
TI Preparation of clinical-grade Zr-89-panitumumab as a positron emission
tomography biomarker for evaluating epidermal growth factor
receptor-targeted therapy
SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
LA English
DT Article
DE 89Zr-immuno-PET; Clinical production; Panitumumab; PET imaging
ID MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; PET; PANITUMUMAB; EGFR
AB Panitumumab is a fully human monoclonal antibody approved for the treatment of epidermal growth factor receptor (EGFR) positive colorectal cancer. Recently, panitumumab has been radiolabeled with Zr-89 and evaluated for its potential to be used as immuno-positron emission tomography (PET) probe for EGFR positive cancers. Interesting preclinical results published by several groups of researchers have prompted us to develop a robust procedure for producing clinical-grade Zr-89-panitumumab as an immuno-PET probe to evaluate EGFR-targeted therapy. In this process, clinical-grade panitumumab is bio-conjugated with desferrioxamine chelate and subsequently radiolabeled with Zr-89 resulting in high radiochemical yield (>70%, n=3) and purity (>98%, n=3). All quality control (QC) tests were performed according to United States Pharmacopeia specifications. QC tests showed that Zr-89-panitumumab met all specifications for human injection. Herein, we describe a step-by-step method for the facile synthesis and QC tests of Zr-89-panitumumab for medical use. The entire process of bioconjugation, radiolabeling, and all QC tests will take about 5h. Because the synthesis is fully manual, two rapid, in-process QC tests have been introduced to make the procedure robust and error free. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Wei, Ling; Shi, Jianfeng; Afari, George; Bhattacharyya, Sibaprasad] ADRD, SAIC Frederick, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Bhattacharyya, S (reprint author), ADRD, SAIC Frederick, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM bhattacharyyas2@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
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 No. 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 US Government. The authors are
grateful to Dr. Lawrence Szajek of cyclotron facility at NIH Bethesda
for providing 89Zr-oxalate.
NR 25
TC 4
Z9 4
U1 3
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0362-4803
EI 1099-1344
J9 J LABELLED COMPD RAD
JI J. Label. Compd. Radiopharm.
PD JAN
PY 2014
VL 57
IS 1
BP 25
EP 35
DI 10.1002/jlcr.3134
PG 11
WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry,
Analytical
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA AA4LZ
UT WOS:000331068400004
PM 24448743
ER
PT J
AU Chen, YC
Nawaz, AA
Zhao, YH
Huang, PH
McCoy, JP
Levine, SJ
Wang, L
Huang, TJ
AF Chen, Yuchao
Nawaz, Ahmad Ahsan
Zhao, Yanhui
Huang, Po-Hsun
McCoy, J. Phillip
Levine, Stewart J.
Wang, Lin
Huang, Tony Jun
TI Standing surface acoustic wave (SSAW)-based microfluidic cytometer
SO LAB ON A CHIP
LA English
DT Article
ID ON-A-CHIP; POLYDIMETHYLSILOXANE PDMS MICROCHANNELS; FLOW-CYTOMETRY;
HIGH-THROUGHPUT; CHANNEL; DEVICE; MICROPARTICLES; SHEATHLESS; PARTICLES;
MICROCHIP
AB The development of microfluidic chip-based cytometers has become an important area due to their advantages of compact size and low cost. Herein, we demonstrate a sheathless microfluidic cytometer which integrates a standing surface acoustic wave (SSAW)-based microdevice capable of 3D particle/cell focusing with a laser-induced fluorescence (LIF) detection system. Using SSAW, our microfluidic cytometer was able to continuously focus microparticles/cells at the pressure node inside a microchannel. Flow cytometry was successfully demonstrated using this system with a coefficient of variation (CV) of less than 10% at a throughput of similar to 1000 events s(-1) when calibration beads were used. We also demonstrated that fluorescently labeled human promyelocytic leukemia cells (HL-60) could be effectively focused and detected with our SSAW-based system. This SSAW-based microfluidic cytometer did not require any sheath flows or complex structures, and it allowed for simple operation over a wide range of sample flow rates. Moreover, with the gentle, bio-compatible nature of low-power surface acoustic waves, this technique is expected to be able to preserve the integrity of cells and other bioparticles.
C1 [Chen, Yuchao; Nawaz, Ahmad Ahsan; Zhao, Yanhui; Huang, Po-Hsun; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA.
[McCoy, J. Phillip; Levine, Stewart J.] NHLBI, Bethesda, MD 20810 USA.
[Wang, Lin] Ascent Bionano Technol Inc, State Coll, PA 16801 USA.
RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA.
EM junhuang@psu.edu
RI Zhao, Yanhui/D-3926-2011; Chen, Yuchao/I-6237-2012; Huang,
Po-Hsun/A-2713-2015; Huang, Tony/A-1546-2009
OI Zhao, Yanhui/0000-0003-1131-8527; Huang, Po-Hsun/0000-0001-9600-0141;
FU National Institutes of Health [1DP2OD007209-01]; National Science
Foundation [ECCS-0824183, ECCS-0801922]; Penn State Center for Nanoscale
Science (MRSEC) [DMR-0820404]; NHLBI Division of Intramural Research
FX We gratefully acknowledge financial support from National Institutes of
Health (Director's New Innovator Award, 1DP2OD007209-01), National
Science Foundation (ECCS-0824183 and ECCS-0801922), and the Penn State
Center for Nanoscale Science (MRSEC) under grant DMR-0820404. J.P.M. and
S.J.L. are supported by the NHLBI Division of Intramural Research.
Components of this work were conducted at the Penn State node of the
NSF-funded National Nanotechnology Infrastructure Network.
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U2 72
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1473-0197
EI 1473-0189
J9 LAB CHIP
JI Lab Chip
PY 2014
VL 14
IS 5
BP 916
EP 923
DI 10.1039/c3lc51139a
PG 8
WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience
& Nanotechnology
SC Biochemistry & Molecular Biology; Chemistry; Science & Technology -
Other Topics
GA AA0KQ
UT WOS:000330784400011
PM 24406848
ER
PT J
AU Chen, Y
Li, S
Gu, Y
Li, P
Ding, X
Wang, L
McCoy, JP
Levine, SJ
Huang, TJ
AF Chen, Yuchao
Li, Sixing
Gu, Yeyi
Li, Peng
Ding, Xiaoyun
Wang, Lin
McCoy, J. Philip
Levine, Stewart J.
Huang, Tony Jun
TI Continuous enrichment of low-abundance cell samples using standing
surface acoustic waves (SSAW)
SO LAB ON A CHIP
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; ON-A-CHIP; MICROFLUIDIC CHANNEL; OPTICAL
MANIPULATION; MICROPARTICLES; SEPARATION; TRAP; CONCENTRATOR; PARTICLES;
SYSTEMS
AB Cell enrichment is a powerful tool in a variety of cellular studies, especially in applications with low-abundance cell types. In this work, we developed a standing surface acoustic wave (SSAW) based microfluidic device for non-contact, continuous cell enrichment. With a pair of parallel interdigital transducers (IDT) deposited on a piezoelectric substrate, a one-dimensional SSAW field was established along disposable micro-tubing channels, generating numerous pressure nodes (and thus numerous cell-enrichment regions). Our method is able to concentrate highly diluted blood cells by more than 100 fold with a recovery efficiency of up to 99%. Such highly effective cell enrichment was achieved without using sheath flow. The SSAW-based technique presented here is simple, bio-compatible, label-free, and sheath-flow-free. With these advantages, it could be valuable for many biomedical applications.
C1 [Chen, Yuchao; Li, Sixing; Li, Peng; Ding, Xiaoyun; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA.
[Li, Sixing; Huang, Tony Jun] Penn State Univ, Huck Inst Life Sci, Cell & Dev Biol CDB Grad Program, University Pk, PA 16802 USA.
[Gu, Yeyi] Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA.
[Wang, Lin] Ascent Bionano Technol Inc, State Coll, PA 16802 USA.
[McCoy, J. Philip; Levine, Stewart J.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA.
EM junhuang@psu.edu
RI Chen, Yuchao/I-6237-2012; Li, Sixing/F-2383-2013; Ding,
Xiaoyun/F-3695-2012; Li, Peng/B-3054-2013; Huang, Tony/A-1546-2009
OI Ding, Xiaoyun/0000-0003-4252-9335; Li, Peng/0000-0002-8332-7142;
FU National Institutes of Health [1DP2OD007209-01]; American Asthma
Foundation (AAF) Scholar Award; National Science Foundation; Penn State
Center for Nanoscale Science (MRSEC) [DMR-0820404]; NHLBI Division of
Intramural Research; NSF-funded National Nanotechnology Infrastructure
Network
FX We gratefully acknowledge financial support from National Institutes of
Health (Director's New Innovator Award, 1DP2OD007209-01), American
Asthma Foundation (AAF) Scholar Award, the National Science Foundation
and the Penn State Center for Nanoscale Science (MRSEC) under grant
DMR-0820404. J.P.M. and S.J.L. are supported by the NHLBI Division of
Intramural Research. Components of this work were conducted at the Penn
State node of the NSF-funded National Nanotechnology Infrastructure
Network.
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PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1473-0197
EI 1473-0189
J9 LAB CHIP
JI Lab Chip
PY 2014
VL 14
IS 5
BP 924
EP 930
DI 10.1039/c3lc51001h
PG 7
WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience
& Nanotechnology
SC Biochemistry & Molecular Biology; Chemistry; Science & Technology -
Other Topics
GA AA0KQ
UT WOS:000330784400012
PM 24413889
ER
PT J
AU Parikh, S
Goldstein, A
Koenig, MK
Scaglia, F
Enns, GM
Saneto, R
Anselm, I
Collins, A
Cohen, BH
DeBrosse, SD
Dimmock, D
Falk, MJ
Ganesh, J
Greene, C
Gropman, AL
Haas, R
Kahler, SG
Kamholz, J
Kendall, F
Korson, MS
Mattman, A
Milone, M
Niyazov, D
Pearl, PL
Reimschisel, T
Salvarinova-Zivkovic, R
Sims, K
Tarnopolsky, M
Tsao, CY
van Hove, J
Walsh, L
Wolfe, LA
AF Parikh, Sumit
Goldstein, Amy
Koenig, Mary Kay
Scaglia, Fernando
Enns, Gregory M.
Saneto, Russell
Anselm, Irina
Collins, Abigail
Cohen, Bruce H.
DeBrosse, Suzanne D.
Dimmock, David
Falk, Marni J.
Ganesh, Jaya
Greene, Carol
Gropman, Andrea L.
Haas, Richard
Kahler, Stephen G.
Kamholz, John
Kendall, Fran
Korson, Mark S.
Mattman, Andre
Milone, Margherita
Niyazov, Dmitriy
Pearl, Phillip L.
Reimschisel, Tyler
Salvarinova-Zivkovic, Ramona
Sims, Katherine
Tarnopolsky, Mark
Tsao, Chang-Yong
van Hove, Johan
Walsh, Laurence
Wolfe, Lynne A.
CA Mitochondrial Med Soc Clinical Dir
MMS Clinical Director's Work Grp
TI Practice patterns of mitochondrial disease physicians in North America.
Part 1: Diagnostic and clinical challenges
SO MITOCHONDRION
LA English
DT Article
DE Mitochondrial disease; Mitochondrial medicine; Clinical guidelines
ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; RESPIRATORY-CHAIN DEFICIENCIES;
OXIDATIVE-PHOSPHORYLATION; DISORDERS; CRITERIA; CHILDREN; AUTISM; TOOL;
DNA
AB Mitochondrial medicine is a young subspecialty. Clinicians have a limited evidence base on which to formulate clinical decisions regarding diagnosis, treatment and patient management. Mitochondrial medicine specialists have cobbled together an informal set of rules and paradigms for preventive care and management based in part on anecdotal experience. The Mitochondrial Medicine Society (MMS) assessed the current state of clinical practice from diagnosis, to preventive care and treatment as provided by various mitochondrial disease specialists in North America. We hope that by obtaining this information we can begin moving towards formulating a set of consensus criteria and establishing standards of care. (C) 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
C1 [Anselm, Irina] Boston Childrens Hosp, Boston, MA USA.
[Collins, Abigail] Univ Colorado, Sch Med, Denver, CO USA.
[Cohen, Bruce H.] Childrens Hosp, Med Ctr Akron, NeuroDev Sci Ctr, Akron, OH USA.
[DeBrosse, Suzanne D.] Univ Hosp Case Med Ctr, Ctr Human Genet, Cleveland, OH USA.
[DeBrosse, Suzanne D.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Dimmock, David] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA.
[Falk, Marni J.] Childrens Hosp Philadelphia, Dept Pediat, Div Human Genet, Philadelphia, PA 19104 USA.
[Falk, Marni J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ganesh, Jaya] Childrens Hosp Philadelphia, Sect Metab Dis, Philadelphia, PA 19104 USA.
[Greene, Carol] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA.
[Gropman, Andrea L.; Pearl, Phillip L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Gropman, Andrea L.] George Washington Univ Hlth Sci, Washington, DC USA.
[Haas, Richard] UCSD Med Ctr, La Jolla, CA USA.
[Haas, Richard] Rady Childrens Hosp San Diego, La Jolla, CA USA.
[Kahler, Stephen G.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
[Kahler, Stephen G.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA.
[Kamholz, John] Wayne State Univ, Detroit, MI USA.
[Kendall, Fran] Virtual Med Practice LLC, Atlanta, GA USA.
[Korson, Mark S.] Tufts Med Ctr, Boston, MA USA.
[Mattman, Andre] Vancouver Gen Hosp, Adult Metab Dis Clin, Vancouver, BC, Canada.
[Milone, Margherita] Mayo Med Ctr, Rochester, MN USA.
[Niyazov, Dmitriy] Ochsner Clin Fdn, Dept Pediat, New Orleans, IA USA.
[Reimschisel, Tyler] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Salvarinova-Zivkovic, Ramona] Univ British Columbia, BC Childrens Hosp, Dept Pediat, Div Biochem Dis, Vancouver, BC V5Z 1M9, Canada.
[Sims, Katherine] Harvard Univ, Sch Med, Boston, MA USA.
[Sims, Katherine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Tarnopolsky, Mark] McMaster Univ, Hamilton, ON, Canada.
[Tsao, Chang-Yong] Nationwide Childrens Hosp, Columbus, OH USA.
[van Hove, Johan] Childrens Hosp Colorado, Denver, CO USA.
[Walsh, Laurence] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Walsh, Laurence] James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA.
[Wolfe, Lynne A.] NIH, Bethesda, MD 20892 USA.
[Parikh, Sumit] Cleveland Clin, Childrens Hosp, Ctr Child Neurol, Cleveland, OH 44195 USA.
[Goldstein, Amy] Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA 15213 USA.
[Koenig, Mary Kay] Univ Texas Houston, Sch Med, Div Child & Adolescent Neurol, Houston, TX USA.
[Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Scaglia, Fernando] Texas Childrens Hosp, Houston, TX 77030 USA.
[Enns, Gregory M.] Stanford Univ, Dept Pediat, Div Med Genet, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA.
[Saneto, Russell] Univ Washington, Seattle Childrens Hosp, Seattle, WA 98195 USA.
RP Parikh, S (reprint author), Cleveland Clin, 9500 Euclid Ave,S60, Cleveland, OH 44195 USA.
EM parikhs@ccf.org
RI Falk, Marni/K-1997-2014; Dimmock, David/I-7913-2015
OI Dimmock, David/0000-0001-6690-2523
NR 21
TC 8
Z9 8
U1 2
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
EI 1872-8278
J9 MITOCHONDRION
JI Mitochondrion
PD JAN
PY 2014
VL 14
BP 26
EP 33
DI 10.1016/j.mito.2013.07.116
PG 8
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA AA2GD
UT WOS:000330912200004
PM 23891656
ER
PT J
AU Tian, LJ
Choi, SC
Murakami, Y
Allen, J
Morse, HC
Qi, CF
Krzewski, K
Coligan, JE
AF Tian, Linjie
Choi, Seung-Chul
Murakami, Yousuke
Allen, Joselyn
Morse, Herbert C., III
Qi, Chen-Feng
Krzewski, Konrad
Coligan, John E.
TI p85 alpha recruitment by the CD300f phosphatidylserine receptor mediates
apoptotic cell clearance required for autoimmunity suppression
SO NATURE COMMUNICATIONS
LA English
DT Article
ID INHIBITORY RECEPTOR; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE;
PHOSPHOINOSITIDE 3-KINASE; CMRF-35-LIKE MOLECULE-1; PSEUDOPOD EXTENSION;
CORPSE CLEARANCE; PHAGOCYTOSIS; ACTIVATION; DISEASE
AB Apoptotic cell (AC) clearance is essential for immune homeostasis. Here we show that mouse CD300f (CLM-1) recognizes outer membrane-exposed phosphatidylserine, and regulates the phagocytosis of ACs. CD300f accumulates in phagocytic cups at AC contact sites. Phosphorylation within CD300f cytoplasmic tail tyrosine-based motifs initiates signals that positively or negatively regulate AC phagocytosis. Y276 phosphorylation is necessary for enhanced CD300f-mediated phagocytosis through the recruitment of the p85 alpha regulatory subunit of phosphatidylinositol-3-kinase (PI3K). CD300f-PI3K association leads to activation of downstream Rac/Cdc42 GTPase and mediates changes of F-actin that drive AC engulfment. Importantly, primary macrophages from CD300f-deficient mice have impaired phagocytosis of ACs. The biological consequence of CD300f deficiency is predisposition to autoimmune disease development, as FcgRIIB-deficient mice develop a systemic lupus erythematosus-like disease at a markedly accelerated rate if CD300f is absent. In this report we identify the mechanism and role of CD300f in AC phagocytosis and maintenance of immune homeostasis.
C1 [Tian, Linjie; Choi, Seung-Chul; Murakami, Yousuke; Allen, Joselyn; Krzewski, Konrad; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Qi, Chen-Feng] NIAID, Pathol Core, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Krzewski, K (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM Konrad.Krzewski@nih.gov; jcoligan@niaid.nih.gov
RI Tian, Linjie/E-6878-2014
FU National Institute of Allergy and Infectious Diseases
FX We thank Dr Silvia Bolland for supplying Fcgr2b-/- mice. We
thank Dr Joel A. Swanson and Dr Samuel Straight for the kind gift of the
human p85-YFP, PLC delta 1-PH-FP and Btk-PH-YFP expression plasmids, Dr
Klaus Hahn for PBD-EYFP plasmid, Dr Shigekazu Nagata for pMX-puro
vector, Dr Debbie C. Thurmond for Cdc42 plasmid and Dr Joseph
Brzostowski for the technical help with the microscopy. We thank Dr
Francisco Borrego and Alexandra Gil-Krzewska for their critical
comments. We also thank Mirna Pena for her work in handling our animal
colony. This study was supported by the intramural programs of the
National Institute of Allergy and Infectious Diseases.
NR 60
TC 17
Z9 17
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2014
VL 5
AR 3146
DI 10.1038/ncomms4146
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA4WK
UT WOS:000331097100010
PM 24477292
ER
PT J
AU Salafia, C
Yampolsky, M
Volk, D
Stodgell, CJ
Katzman, PJ
Culhane, J
Landrigan, P
Szabo, S
Thieux, N
Swanson, J
Dole, N
Varner, MW
Moye, J
Miller, R
AF Salafia, C.
Yampolsky, M.
Volk, D.
Stodgell, C. J.
Katzman, P. J.
Culhane, J.
Landrigan, P.
Szabo, S.
Thieux, N.
Swanson, J.
Dole, N.
Varner, M. W.
Moye, J.
Miller, R.
TI Mapping placental topology from 3D scans, the graphic display of
variation in arborisation across gestation (vol 34, pg A73, 2013)
SO PLACENTA
LA English
DT Correction
C1 [Salafia, C.] Placental Analyt LLC, Larchmont, NY 10538 USA.
[Salafia, C.] New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA.
[Yampolsky, M.] Univ Toronto, Toronto, ON, Canada.
[Volk, D.] Royal Inst Technol, Stockholm, Sweden.
[Stodgell, C. J.; Katzman, P. J.; Culhane, J.; Landrigan, P.; Szabo, S.; Thieux, N.; Swanson, J.; Dole, N.; Varner, M. W.; Moye, J.; Miller, R.] Natl Childrens Study Placenta Consortium, Bethesda, MD USA.
[Stodgell, C. J.; Katzman, P. J.; Miller, R.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Landrigan, P.] Mt Sinai Sch Med, New York, NY USA.
[Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Thieux, N.] S Dakota State Univ, Brookings, SD 57007 USA.
[Swanson, J.] Univ Calif Irvine, Irvine, CA USA.
[Dole, N.] Univ N Carolina, Chapel Hill, NC USA.
[Varner, M. W.] Univ Utah, Salt Lake City, UT USA.
[Moye, J.] NIH, Natl Childrens Study, Bethesda, MD 20892 USA.
RP Salafia, C (reprint author), Placental Analyt LLC, Larchmont, NY 10538 USA.
EM carolyn.salafia@gmail.com
NR 1
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
EI 1532-3102
J9 PLACENTA
JI Placenta
PD JAN
PY 2014
VL 35
IS 1
BP 75
EP 75
DI 10.1016/j.placenta.2013.11.004
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA AA2HU
UT WOS:000330916500012
ER
PT J
AU Sioka, C
Skarulis, MC
Tulloch-Reid, MK
Heiss, JD
Reynolds, JC
AF Sioka, C.
Skarulis, M. C.
Tulloch-Reid, M. K.
Heiss, J. D.
Reynolds, J. C.
TI "Hidden" bone metastasis from thyroid carcinoma: A clinical note
SO REVISTA ESPANOLA DE MEDICINA NUCLEAR E IMAGEN MOLECULAR
LA English
DT Article
DE Follicular thyroid cancer; Metastatic disease; I-131-Iodide; SPECT;
Radioiodine therapy
ID DISTANT METASTASES; CANCER; I-131; DIAGNOSIS
AB The I-131-iodide-(I-131) whole-body scan, for thyroid carcinoma is at times difficult to interpret. In a diagnostic whole body I-131 scan of a patient with follicular carcinoma, a posterior skull lesion was partially hidden by overlapping facial structures. On lateral head view, the abnormality was clearly evident. SPECT/CT and MRI showed the lesion originated in the occipital bone and had enlarged into the posterior fossa. The mass was surgically removed and the patient received 1311 therapy for residual tissue. The study demonstrates a pitfall in the reading of two dimensional radioiodine images which can be overcome by SPECS or lateral imaging. (C) 2013 Elsevier Espana, SI. and SEMNIM. All rights reserved.
C1 [Sioka, C.; Reynolds, J. C.] Dept Radiol & Imaging Sci, Nucl Med Sect, Bethesda, MD 20892 USA.
[Skarulis, M. C.] NIDDK, Diabet Obes & Endocrinol Branch, Bethesda, MD 20892 USA.
[Tulloch-Reid, M. K.] Univ W Indies, Epidemiol Res Unit, Kingston 7, Jamaica.
[Heiss, J. D.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
RP Reynolds, JC (reprint author), Dept Radiol & Imaging Sci, Nucl Med Sect, Bldg 10,Clin Ctr,10 Ctr Dr,Room 1C-461,MSC 1074, Bethesda, MD 20892 USA.
EM jreynolds@mail.cc.nih.gov
OI Heiss, John/0000-0002-3890-0165
FU NIDDK of the National Institutes of Health, Bethesda, MD
[Z01-DK047053-06]
FX This work was supported by the intramural research program of the NIDDK,
project number Z01-DK047053-06 of the National Institutes of Health,
Bethesda, MD.
NR 10
TC 1
Z9 1
U1 2
U2 2
PU ELSEVIER DOYMA SL
PI BARCELONA
PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN
SN 2253-654X
J9 REV ESP MED NUCL IMA
JI Rev. Esp. Med. Nucl. Imagen Mol.
PD JAN-FEB
PY 2014
VL 33
IS 1
BP 36
EP 38
DI 10.1016/j.remn.2013.05.009
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AA2NB
UT WOS:000330930200007
PM 23845451
ER
PT J
AU Olszewski, MB
Chandris, P
Park, BC
Eisenberg, E
Greene, LE
AF Olszewski, Maciej B.
Chandris, Panagiotis
Park, Bum-Chan
Eisenberg, Evan
Greene, Lois E.
TI Disruption of Clathrin-Mediated Trafficking Causes Centrosome
Overduplication and Senescence
SO TRAFFIC
LA English
DT Article
DE centrosome; clathrin; DNA damage; endocytosis; overduplication;
senescence; trafficking
ID G-ASSOCIATED KINASE; INDUCED DNA-DAMAGE; LABILE IRON POOL; IN-VIVO;
CELLULAR SENESCENCE; HUMAN-CELLS; ENDOCYTOSIS; DYNAMIN; REPLICATION;
SPINDLE
AB The Hsc70 cochaperone, G cyclin-associated kinase (GAK), has been shown to be essential for the chaperoning of clathrin by Hsc70 in the cell. In this study, we used conditional GAK knockout mouse embryonic fibroblasts (MEFs) to determine the effect of completely inhibiting clathrin-dependent trafficking on the cell cycle. After GAK was knocked out, the cells developed the unusual phenotype of having multiple centrosomes, but at the same time failed to divide and ultimately became senescent. To explain this phenotype, we examined the signaling profile and found that mitogenic stimulation of the GAK KO cells and the control cells were similar except for increased phosphorylation of Akt. In addition, the disruption of intracellular trafficking caused by knocking out GAK destabilized the lysosomal membranes, resulting in DNA damage due to iron leakage. Knocking down clathrin heavy chain or inhibiting dynamin largely reproduced the GAK KO phenotype, but inhibiting only clathrin-mediated endocytosis by knocking down adaptor protein (AP2) caused growth arrest and centrosome overduplication, but no DNA damage or senescence. We conclude that disruption of clathrin-dependent trafficking induces senescence accompanied by centrosome overduplication because of a combination of DNA damage and changes in mitogenic signaling that uncouples centrosomal duplication from DNA replication.
C1 [Olszewski, Maciej B.; Chandris, Panagiotis; Park, Bum-Chan; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Olszewski, MB (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM molszewski@iimcb.gov.pl; greenel@helix.nih.gov
RI Olszewski, Maciej/C-2021-2015
OI Olszewski, Maciej/0000-0003-0961-0801
FU Foundation for Polish Science grant 'Kolumb'
FX M. B. O. was supported by Foundation for Polish Science grant 'Kolumb'.
NR 48
TC 5
Z9 5
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-9219
EI 1600-0854
J9 TRAFFIC
JI Traffic
PD JAN
PY 2014
VL 15
IS 1
BP 60
EP 77
DI 10.1111/tra.12132
PG 18
WC Cell Biology
SC Cell Biology
GA AA7TR
UT WOS:000331300300004
PM 24138026
ER
PT J
AU Szabon-Watola, MI
Ulatowski, SV
George, KM
Hayes, CD
Steiger, SA
Natale, NR
AF Szabon-Watola, Monika I.
Ulatowski, Sarah V.
George, Kathleen M.
Hayes, Christina D.
Steiger, Scott A.
Natale, Nicholas R.
TI Fluorescent probes of the isoxazole-dihydropyridine scaffold: MDR-1
binding and homology model
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Multidrug resistance transporter; Isoxazole; Dihydropyridine; Homology
model
ID MULTIDRUG-RESISTANCE MODIFIERS; P-GLYCOPROTEIN INHIBITORS; DRUG
TRANSPORTER; IN-VITRO; 4-ISOXAZOLYL-1,4-DIHYDROPYRIDINES; MODULATORS;
1,4-DIHYDROPYRIDINES; DERIVATIVES; HOMODIMERS; DOCKING
AB Isoxazole-1,4-dihydropyridines (IDHPs) were tethered to fluorescent moieties using double activation via a lanthanide assisted Weinreb amidation. IDHP-fluorophore conjugate 3c exhibits the highest binding to date for IDHPs at the multidrug-resistance transporter (MDR-1), and IDHP-fluorophore conjugates 3c and 7 distribute selectively in SH-SY5Y cells. A homology model for IDHP binding at MDR-1 is presented which represents our current working hypothesis. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ulatowski, Sarah V.; George, Kathleen M.; Hayes, Christina D.; Steiger, Scott A.; Natale, Nicholas R.] Univ Montana, NIH COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
[Szabon-Watola, Monika I.; Natale, Nicholas R.] Univ Idaho, Dept Chem, Moscow, ID 83843 USA.
RP Natale, NR (reprint author), Univ Montana, NIH COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
EM nicholas.natale@umontana.edu
FU NIH [NS038444, 5U01ES016102-02, P20RR015583]; NSF REU [0649306]; Malcolm
and Carol Renfrew Scholarship; National Institute of Mental Health's
Psychoactive Drug Screening Program (NIMH PDSP) [HHSN-271-2008-00025-C]
FX The authors thank NIH for grants NS038444 (N.N., M. I. S.),
5U01ES016102-02 (K. M. G., S. V. U.), and P20RR015583 (N.N., S. S.). C.
D. H. thanks the NSF REU Award Number 0649306. M. I. S. thanks the
Malcolm and Carol Renfrew Scholarship. We thank Dr. Alex Blumenfeld for
VT NMR and Dr. Gary Knerr for able assistance in FAB MS while at the
University of Idaho. We thank Dr. Mike Braden and Dave Holley of the
Core Facility for Molecular Computation (UM) for helpful discussions
during pharmacophore modeling.; MDR1 data was generously provided by the
National Institute of Mental Health's Psychoactive Drug Screening
Program (NIMH PDSP), Contract # HHSN-271-2008-00025-C (NIMH PDSP). The
NIMH PDSP is Directed by Bryan L. Roth MD, Ph.D. at the University of
North Carolina at Chapel Hill and Project Officer Jamie Driscoll at
NIMH, Bethesda MD, USA.
NR 49
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Z9 3
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JAN 1
PY 2014
VL 24
IS 1
BP 117
EP 121
DI 10.1016/j.bmcl.2013.11.068
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 281PT
UT WOS:000329114200019
PM 24342237
ER
PT J
AU Kim, MS
Ki, Y
Ahn, SY
Yoon, S
Kim, SE
Park, HG
Sun, W
Son, K
Cui, M
Choi, S
Pearce, LV
Esch, TE
DeAndrea-Lazarus, IA
Blumberg, PM
Lee, J
AF Kim, Myeong Seop
Ki, Yooran
Ahn, Song Yeon
Yoon, Suyoung
Kim, Sung-Eun
Park, Hyeung-Geun
Sun, Wei
Son, Karam
Cui, Minghua
Choi, Sun
Pearce, Larry V.
Esch, Timothy E.
DeAndrea-Lazarus, Ian A.
Blumberg, Peter M.
Lee, Jeewoo
TI Asymmetric synthesis and receptor activity of chiral simplified
resiniferatoxin (sRTX) analogues as transient receptor potential
vanilloid 1 (TRPV1) ligands
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Vanilloid receptor 1; TRPV1 antagonist; Capsaicin; Resiniferatoxin;
Molecular modeling
ID CAPSAICIN RECEPTORS; ANTAGONISTS; DERIVATIVES
AB The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Kim, Myeong Seop; Ki, Yooran; Ahn, Song Yeon; Yoon, Suyoung; Kim, Sung-Eun; Park, Hyeung-Geun; Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
[Sun, Wei] Shenyang Pharmaceut Univ, Shenyang 110016, Liaoning, Peoples R China.
[Son, Karam; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Natl Leading Res Lab Mol Modeling & Drug Design, Seoul 120750, South Korea.
[Son, Karam; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Global Top Res Program 5, Seoul 120750, South Korea.
[Pearce, Larry V.; Esch, Timothy E.; DeAndrea-Lazarus, Ian A.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
FU National Research Foundation of Korea (NRF) [2007-0056817]; NLRL program
[2011-0028885]; Korea government MSIP; Intramural Research Program of
the National Institutes of Health, Center for Cancer Research, National
Cancer Institute [Z1A BC 005270]
FX This research was supported by the National Research Foundation of Korea
(NRF) Grant (2007-0056817) and NLRL program Grant (2011-0028885) funded
by the Korea government MSIP, and was supported in part by the
Intramural Research Program of the National Institutes of Health, Center
for Cancer Research, National Cancer Institute (Project Z1A BC 005270).
NR 20
TC 5
Z9 5
U1 2
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JAN 1
PY 2014
VL 24
IS 1
BP 382
EP 385
DI 10.1016/j.bmcl.2013.10.064
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 281PT
UT WOS:000329114200075
PM 24321344
ER
PT J
AU Kleensang, A
Maertens, A
Rosenberg, M
Fitzpatrick, S
Lamb, J
Auerbach, S
Brennan, R
Crofton, KM
Gordon, B
Fornace, AJ
Gaido, K
Gerhold, D
Haw, R
Henney, A
Ma'ayan, A
McBride, M
Monti, S
Ochs, MF
Pandey, A
Sharan, R
Stierum, R
Tugendreich, S
Willett, C
Wittwehr, C
Xia, JG
Patton, GW
Arvidson, K
Bouhifd, M
Hogberg, HT
Luechtefeld, T
Smirnova, L
Zhao, L
Adeleye, Y
Kanehisa, M
Carmichael, P
Andersen, ME
Hartung, T
AF Kleensang, Andre
Maertens, Alexandra
Rosenberg, Michael
Fitzpatrick, Suzanne
Lamb, Justin
Auerbach, Scott
Brennan, Richard
Crofton, Kevin M.
Gordon, Ben
Fornace, Albert J., Jr.
Gaido, Kevin
Gerhold, David
Haw, Robin
Henney, Adrian
Ma'ayan, Avi
McBride, Mary
Monti, Stefano
Ochs, Michael F.
Pandey, Akhilesh
Sharan, Roded
Stierum, Rob
Tugendreich, Stuart
Willett, Catherine
Wittwehr, Clemens
Xia, Jianguo
Patton, Geoffrey W.
Arvidson, Kirk
Bouhifd, Mounir
Hogberg, Helena T.
Luechtefeld, Thomas
Smirnova, Lena
Zhao, Liang
Adeleye, Yeyejide
Kanehisa, Minoru
Carmichael, Paul
Andersen, Melvin E.
Hartung, Thomas
TI Pathways of Toxicity
SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
LA English
DT Article
DE systems toxicology; pathways of toxicity; adverse outcome pathways; in
vitro toxicology; human toxome
ID BIOLOGICAL NETWORKS; SYSTEMS TOXICOLOGY; 21ST-CENTURY; THOUGHT; FOOD;
VALIDATION; TOXICOGENOMICS; PERSPECTIVES; TECHNOLOGIES; INTEGRATION
AB Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as "A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants". It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities.
C1 [Kleensang, Andre; Maertens, Alexandra; Bouhifd, Mounir; Hogberg, Helena T.; Luechtefeld, Thomas; Smirnova, Lena; Zhao, Liang; Hartung, Thomas] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA.
[Rosenberg, Michael; McBride, Mary] Agilent Technol, Santa Clara, CA USA.
[Fitzpatrick, Suzanne; Gaido, Kevin] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Lamb, Justin] Genometry Inc, Cambridge, MA USA.
[Auerbach, Scott] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Brennan, Richard] Thomson Reuters Inc, Carlsbad, CA USA.
[Crofton, Kevin M.] US EPA, Off Res & Dev, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA.
[Gordon, Ben] MIT, Dept Biol Engn, Cambridge, MA 02139 USA.
[Fornace, Albert J., Jr.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC USA.
[Fornace, Albert J., Jr.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Gerhold, David] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Haw, Robin] Ontario Inst Canc Res, Reactome, Toronto, ON, Canada.
[Henney, Adrian] Heidelberg Univ, German Virtual Liver Network, Heidelberg, Germany.
[Ma'ayan, Avi] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY USA.
[Monti, Stefano] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA.
[Ochs, Michael F.] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Sharan, Roded] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel.
[Stierum, Rob] TNO Hlth Living Microbiol & Syst Biol, Zeist, Netherlands.
[Tugendreich, Stuart] Ingenu Syst Inc, Redwood City, CA USA.
[Willett, Catherine] Humane Soc United States, Washington, DC USA.
[Wittwehr, Clemens] Commiss European Communities, Joint Res Ctr, Syst Toxicol Unit, I-21020 Ispra, Italy.
[Xia, Jianguo] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada.
[Patton, Geoffrey W.; Arvidson, Kirk] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD USA.
[Adeleye, Yeyejide; Carmichael, Paul] Unilever, Safety & Environm Assurance Ctr, Sharnbrook, Beds, England.
[Kanehisa, Minoru] Kyoto Univ, Inst Chem Res, Kyoto 606, Japan.
[Andersen, Melvin E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA.
[Hartung, Thomas] Univ Konstanz, CAAT Europe, Constance, Germany.
RP Hartung, T (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, 615 North Wolfe St,W7032, Baltimore, MD 21205 USA.
EM thartung@jhsph.edu
RI Crofton, Kevin/J-4798-2015; Zhao, Liang/I-4777-2015;
OI Crofton, Kevin/0000-0003-1749-9971; Zhao, Liang/0000-0002-2126-6778;
Kleensang, Andre/0000-0002-4564-7399
FU Unilever; NIH transformative research project on "Mapping the Human
Toxome by Systems Toxicology" [R01ES020750]; FDA grant "DNTox-21c
Identification of pathways of developmental neurotoxicity for high
throughput testing by metabolomics" [U01FD004230]
FX This CAAT workshop on Pathways of Toxicity was made possible by support
from Unilever and the extensive discussions and experiences of the NIH
transformative research project on "Mapping the Human Toxome by Systems
Toxicology" (R01ES020750) and FDA grant "DNTox-21c Identification of
pathways of developmental neurotoxicity for high throughput testing by
metabolomics" (U01FD004230).
NR 58
TC 38
Z9 39
U1 1
U2 14
PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
PI HEILDEBERG
PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY
SN 1868-596X
EI 1868-8551
J9 ALTEX-ALTERN ANIM EX
JI ALTEX-Altern. Anim. Exp.
PY 2014
VL 31
IS 1
BP 53
EP 61
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 304MF
UT WOS:000330750300007
PM 24127042
ER
PT J
AU Juberg, DR
Borghoff, SJ
Becker, RA
Casey, W
Hartung, T
Holsapple, MP
Marty, MS
Mihaich, EM
Van der Kraak, G
Wade, MG
Willett, CE
Andersen, ME
Borgert, CJ
Coady, KK
Dourson, ML
Fowle, JR
Gray, LE
Lamb, JC
Ortego, LS
Schug, TT
Toole, CM
Zorrilla, LM
Kroner, OL
Patterson, J
Rinckel, LA
Jones, BR
AF Juberg, Daland R.
Borghoff, Susan J.
Becker, Richard A.
Casey, Warren
Hartung, Thomas
Holsapple, Michael P.
Marty, M. Sue
Mihaich, Ellen M.
Van der Kraak, Glen
Wade, Michael G.
Willett, Catherine E.
Andersen, Melvin E.
Borgert, Christopher J.
Coady, Katherine K.
Dourson, Michael L.
Fowle, John R., III
Gray, L. Earl
Lamb, James C.
Ortego, Lisa S.
Schug, Thaddeus T.
Toole, Colleen M.
Zorrilla, Leah M.
Kroner, Oliver L.
Patterson, Jacqueline
Rinckel, Lori A.
Jones, Brett R.
TI Lessons Learned, Challenges, and Opportunities: The US Endocrine
Disruptor Screening Program
SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
LA English
DT Article
DE endocrine disruptors; Tier 1; screening; systematic review; Endocrine
Disruptor Screening Program
ID CHEMICALS; EXPOSURE; ASSAYS
AB In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency (EPA) to implement a screening program to investigate the potential of pesticide chemicals and drinking water contaminants to adversely affect endocrine pathways. Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP) to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening assays and to produce standardized and harmonized test guidelines for regulatory application. In 2009, the EPA issued the first set of test orders for EDSP screening and a total of 50 pesticide actives and 2 inert ingredients have been evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro assays and six in vivo assays).
To provide a framework for retrospective analysis of the data generated and to collect the insight of multiple stakeholders involved in the testing, more than 240 scientists from government, industry, academia, and non-profit organizations recently participated in a workshop titled "Lessons Learned, Challenges, Opportunities: The U.S. Endocrine Disruptor Screening Program." The workshop focused on the science and experience to date and was organized into three focal sessions: (a) Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical Applications of Tier 1 Data; and (c) Indications and Opportunities for Future Endocrine Testing. A number of key findings and recommendations related to future EDSP evaluations emanated from the collective sessions.
C1 [Juberg, Daland R.] Dow AgroSci LLC, Indianapolis, IN 46268 USA.
[Borghoff, Susan J.] ToxStrategies Inc, Cary, NC USA.
[Becker, Richard A.] Amer Chem Council, Washington, DC USA.
[Casey, Warren; Schug, Thaddeus T.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Hartung, Thomas] Johns Hopkins Univ, Baltimore, MD USA.
[Hartung, Thomas] Univ Konstanz, Constance, Germany.
[Holsapple, Michael P.] Batelle, Columbus, OH USA.
[Marty, M. Sue; Coady, Katherine K.] Dow Chem Co USA, Saginaw, MI USA.
[Mihaich, Ellen M.] ER2 & Endocrine Policy Forum, Durham, NC USA.
[Van der Kraak, Glen] Univ Guelph, Guelph, ON N1G 2W1, Canada.
[Wade, Michael G.] Hlth Canada, Ottawa, ON K1A 0L2, Canada.
[Willett, Catherine E.] Humane Soc United States, Washington, DC USA.
[Andersen, Melvin E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA.
[Borgert, Christopher J.] Appl Pharmacol & Toxicol Inc, Gainesville, FL USA.
[Dourson, Michael L.; Kroner, Oliver L.; Patterson, Jacqueline] Toxicol Excellence Risk Assessment, Cincinnati, OH USA.
[Fowle, John R., III] Sci Inform, Pittsboro, NC USA.
[Gray, L. Earl] US EPA, Res Triangle Pk, NC 27711 USA.
[Lamb, James C.] Exponent, Alexandria, VA USA.
[Ortego, Lisa S.] Bayer CropSci, Raleigh, NC USA.
[Toole, Colleen M.] Ceetox, Kalamazoo, MI USA.
[Zorrilla, Leah M.; Rinckel, Lori A.; Jones, Brett R.] Integrated Lab Syst Inc, Morrisville, NC USA.
RP Juberg, DR (reprint author), Dow AgroSci LLC, 9330 Zionsville Rd, Indianapolis, IN 46268 USA.
EM drjuberg@dow.com
NR 23
TC 12
Z9 12
U1 6
U2 24
PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH
PI HEILDEBERG
PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY
SN 1868-596X
EI 1868-8551
J9 ALTEX-ALTERN ANIM EX
JI ALTEX-Altern. Anim. Exp.
PY 2014
VL 31
IS 1
BP 63
EP 78
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 304MF
UT WOS:000330750300008
PM 24114257
ER
PT J
AU Crews, DC
Kuczmarski, MF
Grubbs, V
Hedgeman, E
Shahinian, VB
Evans, MK
Zonderman, AB
Burrows, NR
Williams, DE
Saran, R
Powe, NR
AF Crews, Deidra C.
Kuczmarski, Marie Fanelli
Grubbs, Vanessa
Hedgeman, Elizabeth
Shahinian, Vahakn B.
Evans, Michele K.
Zonderman, Alan B.
Burrows, Nilka Rios
Williams, Desmond E.
Saran, Rajiv
Powe, Neil R.
CA Ctr Disease Control & Preven
TI Effect of Food Insecurity on Chronic Kidney Disease in Lower-Income
Americans
SO AMERICAN JOURNAL OF NEPHROLOGY
LA English
DT Article
DE Socioeconomic status; Disparity; Nutrition
ID GLOMERULAR-FILTRATION-RATE; SOCIOECONOMIC-STATUS; NATIONAL-HEALTH;
RACIAL DISPARITIES; SERUM CREATININE; UNITED-STATES; POVERTY;
PREVALENCE; NUTRITION; ALBUMINURIA
AB Background: The relation of food insecurity (inability to acquire nutritionally adequate and safe foods) and chronic kidney disease (CKD) is unknown. We examined whether food insecurity is associated with prevalent CKD among lower-income individuals in both the general US adult population and an urban population. Methods: We conducted cross-sectional analyses of lower-income participants of the National Health and Nutrition Examination Survey (NHANES) 2003-2008 (n = 9,126) and the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (n = 1,239). Food insecurity was defined based on questionnaires and CKD was defined by reduced estimated glomerular filtration rate or albuminuria; adjustment was performed with multivariable logistic regression. Results: In NHANES, the age-adjusted prevalence of CKD was 20.3, 17.6, and 15.7% for the high, marginal, and no food insecurity groups, respectively. Analyses adjusting for sociodemographics and smoking status revealed high food insecurity to be associated with greater odds of CKD only among participants with either diabetes (OR = 1.67, 95% CI: 1.14-2.45 comparing high to no food insecurity groups) or hypertension (OR = 1.37, 95% CI: 1.03-1.82). In HANDLS, the age-adjusted CKD prevalence was 5.9 and 4.6% for those with and without food insecurity, respectively (p = 0.33). Food insecurity was associated with a trend towards greater odds of CKD (OR = 1.46, 95% CI: 0.98-2.18) with no evidence of effect modification across diabetes, hypertension, or obesity subgroups. Conclusion: Food insecurity may contribute to disparities in kidney disease, especially among persons with diabetes or hypertension, and is worthy of further study. (C) 2014 S. Karger AG, Basel
C1 [Crews, Deidra C.] Johns Hopkins Med Inst, Dept Med, Div Nephrol, Baltimore, MD 21205 USA.
[Crews, Deidra C.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
[Kuczmarski, Marie Fanelli] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA.
[Grubbs, Vanessa] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA.
[Hedgeman, Elizabeth; Shahinian, Vahakn B.; Saran, Rajiv] Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI 48109 USA.
[Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Baltimore, MD USA.
[Burrows, Nilka Rios; Williams, Desmond E.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA.
[Powe, Neil R.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA USA.
RP Crews, DC (reprint author), Johns Hopkins Univ, Sch Med, Div Nephrol, Johns Hopkins Bayview Med Ctr, 301 Mason F Lord Dr,Suite 2500, Baltimore, MD 21224 USA.
EM dcrews1@jhmi.edu
RI Nguyen, Giang/D-9027-2016
FU CDC [1U58DP003839-01]; Intramural Research Program of the NIA, National
Institutes of Health; Harold Amos Medical Faculty Development Program of
the Robert Wood Johnson Foundation; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [K23 DK093710]; NIDDK [R01
DK78124]
FX This project was supported under a cooperative agreement from the CDC,
grant 1U58DP003839-01. The findings and conclusions in this report are
those of the authors and do not necessarily represent the official
position of the CDC.; This work was supported by the Intramural Research
Program of the NIA, National Institutes of Health. Dr. Crews and Dr.
Grubbs were supported by the Harold Amos Medical Faculty Development
Program of the Robert Wood Johnson Foundation.; Dr. Grubbs was also
supported by grant K23 DK093710 from the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK). Dr. Powe was partially
supported by grant R01 DK78124 from the NIDDK.
NR 52
TC 7
Z9 7
U1 1
U2 10
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0250-8095
EI 1421-9670
J9 AM J NEPHROL
JI Am. J. Nephrol.
PY 2014
VL 39
IS 1
BP 27
EP 35
DI 10.1159/000357595
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 302VF
UT WOS:000330632300005
PM 24434743
ER
PT J
AU Church, SE
Jensen, SM
Antony, PA
Restifo, NP
Fox, BA
AF Church, Sarah E.
Jensen, Shawn M.
Antony, Paul A.
Restifo, Nicholas P.
Fox, Bernard A.
TI Tumor-specific CD4(+) T cells maintain effector and memory
tumor-specific CD8(+) T cells
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LARGE ESTABLISHED MELANOMA; ADOPTIVE IMMUNOTHERAPY; IN-VIVO; CANCER
REGRESSION; METASTATIC MELANOMA; LYMPHOPENIC HOSTS; INTERFERON-GAMMA;
IFN-GAMMA; LYMPHOCYTES; HELP
C1 [Church, Sarah E.; Jensen, Shawn M.; Fox, Bernard A.] Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Robert W Franz Canc Res Ctr, Providence Canc Ctr, Portland, OR 97213 USA.
[Church, Sarah E.; Fox, Bernard A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA.
[Antony, Paul A.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Ctr Canc, Baltimore, MD 21201 USA.
[Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Fox, Bernard A.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
RP Fox, BA (reprint author), Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, 2N56 North Pavil,4805 NE Glisan St, Portland, OR 97213 USA.
EM foxb@foxlab.org
OI Restifo, Nicholas P./0000-0003-4229-4580
FU NCI [CA 80564]; NIH [T32 AI007472]
FX We would like to thank Dan Haley for assistance with initial set-up of
flow panels and sorting experiments, Tacy Brotherton and Amanda Lyon for
breeding and caring for the mice, Dr. Dubay for initial help setting up
polychromatic flow analysis, and Michael Afentoulis for help with
experiments. We would like to additionally thank Dr. Urba, Dr. van de
Ven, Dr. Twitty, Dr. Parker, Dr. Davey, and Dr. Weinberg for reviewing
this manuscript and for thoughtful discussions throughout this work.
Funding sources: NCI CA 80564, NIH T32 AI007472.
NR 49
TC 34
Z9 35
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JAN
PY 2014
VL 44
IS 1
BP 69
EP 79
PG 11
WC Immunology
SC Immunology
GA AA0RA
UT WOS:000330803400009
PM 24114780
ER
PT J
AU Liu, BY
Zhong, S
Malecek, K
Johnson, LA
Rosenberg, SA
Zhu, C
Krogsgaard, M
AF Liu, Baoyu
Zhong, Shi
Malecek, Karolina
Johnson, Laura A.
Rosenberg, Steven A.
Zhu, Cheng
Krogsgaard, Michelle
TI 2D TCR-pMHC-CD8 kinetics determines T-cell responses in a
self-antigen-specific TCR system
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; LIGAND BINDING-KINETICS; RECEPTOR
AFFINITY; CD8 CORECEPTOR; ACTIVATION; IMPACT; SELECTION; MEMBRANE;
RESPONSIVENESS; MICROTOPOLOGY
C1 [Liu, Baoyu; Zhu, Cheng] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
[Zhu, Cheng] Georgia Inst Technol, Woodruff Sch Mech Engn, Atlanta, GA 30332 USA.
[Zhu, Cheng] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
[Zhong, Shi; Malecek, Karolina; Krogsgaard, Michelle] NYU, Sch Med, NYU Canc Inst, New York, NY 10016 USA.
[Malecek, Karolina; Krogsgaard, Michelle] NYU, Sch Med, Program Struct Biol, New York, NY 10016 USA.
[Krogsgaard, Michelle] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Johnson, Laura A.; Rosenberg, Steven A.] NCI, Ctr Canc Res, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
RP Krogsgaard, M (reprint author), NYU, Sch Med, Dept Pathol, 522 First Ave,Smilow 1311, New York, NY 10016 USA.
EM cheng.zhu@bme.gatech.edu; Michelle.Krogsgaard@nyumc.org
RI Liu, Baoyu/C-4911-2009
OI Liu, Baoyu/0000-0002-0798-6314
FU Pew Trust; National Institute of Health [NCI 1U01CA137070, NIGMS
5R01GM085586, R01GM096187, R56AI038282]; American Cancer Society
[RSG-09-070-01-LIB]; Cancer Research Investigator grant
FX We thank New York University and Georgia Institute of Technology flow
cytometry cores for technical assistance. We thank Dr. David Kranz and
Dr. Michael Dustin for providing cell lines and plasmids, Katelyn McGary
and Kevin Huang for assistance in soluble protein productions, and Dr.
Jeffrey Donnell for critical reading of the manuscript. M.K. was a Pew
Scholar in the Biomedical Sciences supported by the Pew Trust. This work
was supported by the National Institute of Health grants NCI
1U01CA137070 and NIGMS 5R01GM085586 (to M.K.) and R01GM096187 and
R56AI038282 (to C.Z.), an American Cancer Society Research Scholar grant
RSG-09-070-01-LIB (to M.K), and a Cancer Research Investigator grant (to
M.K.).
NR 54
TC 13
Z9 13
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JAN
PY 2014
VL 44
IS 1
BP 239
EP 250
PG 12
WC Immunology
SC Immunology
GA AA0RA
UT WOS:000330803400024
PM 24114747
ER
PT J
AU Laughon, SK
McLain, AC
Sundaram, R
Catov, JM
Louis, GMB
AF Laughon, S. Katherine
McLain, Alexander C.
Sundaram, Rajeshwari
Catov, Janet M.
Louis, Germaine M. Buck
TI Maternal Lipid Change in Relation to Length of Gestation: A Prospective
Cohort Study with Preconception Enrollment of Women
SO GYNECOLOGIC AND OBSTETRIC INVESTIGATION
LA English
DT Article
DE Cholesterol; Lipids; Miscarriage; Preterm birth; Triglycerides
ID PRETERM BIRTH; PREGNANCY; SERUM; MORTALITY; WINDOWS; MOTHERS; RISK; LIFE
AB Background/Aims:We sought to investigate the association between preconception serum lipids and their daily rate of change in relation to length of gestation. Methods: In a cohort of 70 women, 61(87%) became pregnant, resulting in 48 (69%) live births. Serum lipid measurements (in milligrams per deciliter) included total cholesterol, free cholesterol, triglycerides and phospholipids at preconception, upon human chorionic gonadotropin-confirmed pregnancy and following pregnancy loss (<14 weeks) or post partum. Pregnancy outcome (loss, preterm and term delivery) and gestational length were modeled relative to daily rate of change in lipids using multinomial regression and Cox proportional hazards models, respectively, adjusting for body mass index and smoking. Results: A rate of triglyceride change below the median was associated with an increased risk for pregnancy loss compared with term birth (adjusted odds ratio: 9.02; 95% CI: 1.62-50.30). A rate of triglyceride change of <= 3.01 mg/dl per day versus above the median was associated with a trend for increased risk of pregnancy loss or preterm (<37 weeks) birth (adjusted hazard ratio: 1.77; 95% CI: 0.94-3.33). Conclusion: A low rate of triglyceride change during early pregnancy may be a signal of risk of pregnancy loss or preterm birth. Lipids offer promise for identifying pregnancies at risk for adverse outcomes. (C) 2013 S. Karger AG, Basel
C1 [Laughon, S. Katherine] Eunice Kennedy Shriyer Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Rockville, MD USA.
[McLain, Alexander C.; Sundaram, Rajeshwari] Eunice Kennedy Shriyer Natl Inst Child Hlth & Hum, Biostat Branch, NIH, Rockville, MD USA.
[Louis, Germaine M. Buck] Eunice Kennedy Shriyer Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Catov, Janet M.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Serv, Pittsburgh, PA USA.
[Catov, Janet M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
RP Laughon, SK (reprint author), NICHD, Epidemiol Branch, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM laughonsk@mail.nih.gov
OI McLain, Alexander/0000-0002-5475-0670; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis,
Germaine/0000-0002-1774-4490; Grantz, Katherine/0000-0003-0276-8534
FU Great Lakes Protection Fund [RM791-3021]; Agency for Toxic Substances
and Disease Registry [H751ATH298338]; Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported in part with funding from the Great Lakes
Protection Fund (RM791-3021), the Agency for Toxic Substances and
Disease Registry (H751ATH298338) and the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 20
TC 4
Z9 4
U1 0
U2 1
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0378-7346
EI 1423-002X
J9 GYNECOL OBSTET INVES
JI Gynecol.Obstet.Invest.
PY 2014
VL 77
IS 1
BP 6
EP 13
DI 10.1159/000355100
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 302LR
UT WOS:000330606500002
PM 24334826
ER
PT J
AU Bergamaschi, MM
Queiroz, RHC
Chagas, MHN
Linares, IMP
Arrais, KC
de Oliveira, DCG
Queiroz, ME
Nardi, AE
Huestis, MA
Hallak, JEC
Zuardi, AW
Moreira, FA
Crippa, JAS
AF Bergamaschi, Mateus M.
Queiroz, Regina H. C.
Chagas, Marcos H. N.
Linares, Ila M. P.
Arrais, Katia C.
de Oliveira, Danielle C. G.
Queiroz, Maria E.
Nardi, Antonio E.
Huestis, Marilyn A.
Hallak, Jaime E. C.
Zuardi, Antonio W.
Moreira, Fabricio A.
Crippa, Jose A. S.
TI Rimonabant effects on anxiety induced by simulated public speaking in
healthy humans: a preliminary report
SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE anxiety; public speaking test; rimonabant; SR141716; CB1 receptor
ID ALCOHOL SCREENING-TEST; PSYCHOMETRIC PROPERTIES; CANNABINOID RECEPTORS;
CLINICAL ANXIETY; INHIBITION; DEPRESSION; DISORDERS; INVENTORY;
BLOCKADE; BEHAVIOR
AB ObjectiveWe investigated the hypothesis that rimonabant, a cannabinoid antagonist/inverse agonist, would increase anxiety in healthy subjects during a simulation of the public speaking test.
MethodsParticipants were randomly allocated to receive oral placebo or 90mg rimonabant in a double-blind design. Subjective effects were measured by Visual Analogue Mood Scale. Physiological parameters, namely arterial blood pressure and heart rate, also were monitored.
ResultsTwelve participants received oral placebo and 12 received 90mg rimonabant. Rimonabant increased self-reported anxiety levels during the anticipatory speech and performance phase compared with placebo. Interestingly, rimonabant did not modulate anxiety prestress and was not associated with sedation, cognitive impairment, discomfort, or blood pressure changes.
ConclusionsCannabinoid-1 antagonism magnifies the responses to an anxiogenic stimulus without interfering with the prestress phase. These data suggest that the endocannabinoid system may work on-demand to counteract the consequences of anxiogenic stimuli in healthy humans. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Bergamaschi, Mateus M.; Chagas, Marcos H. N.; Linares, Ila M. P.; Arrais, Katia C.; de Oliveira, Danielle C. G.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Crippa, Jose A. S.] Univ Sao Paulo, Dept Neurosci & Behav, Ribeirao Preto Med Sch, BR-14048900 Ribeirao Preto, SP, Brazil.
[Bergamaschi, Mateus M.; Queiroz, Regina H. C.] Univ Sao Paulo, Dept Clin Toxicol & Food Sci Anal, Sch Pharmaceut Sci Ribeirao Preto, BR-14048900 Ribeirao Preto, SP, Brazil.
[Bergamaschi, Mateus M.; Queiroz, Regina H. C.; Chagas, Marcos H. N.; Linares, Ila M. P.; Arrais, Katia C.; de Oliveira, Danielle C. G.; Nardi, Antonio E.; Hallak, Jaime E. C.; Zuardi, Antonio W.; Moreira, Fabricio A.; Crippa, Jose A. S.] Natl Inst Translat Med INCT TM, CNPq, Rio De Janeiro, Brazil.
[Queiroz, Maria E.] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, BR-14048900 Ribeirao Preto, SP, Brazil.
[Nardi, Antonio E.] Univ Fed Rio de Janeiro, Lab Pan & Respirat, Inst Psychiat, Rio De Janeiro, Brazil.
[Huestis, Marilyn A.] NIDA, IRP, NIH, Baltimore, MD USA.
[Moreira, Fabricio A.] Univ Fed Minas Gerais, Dept Pharmacol, Inst Biol Sci, Belo Horizonte, MG, Brazil.
RP Bergamaschi, MM (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, Av Bandeirantes,3900 Hosp Clin Terceiro Andar, BR-14048900 Ribeirao Preto, SP, Brazil.
EM mateusbergamaschi@yahoo.com.br
RI Chagas, Marcos Hortes N./D-9850-2012
OI Chagas, Marcos Hortes N./0000-0003-3752-7984
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2009/11805-4];
CNPq (Brazil)
FX The authors acknowledge Sandra Bernardo and Selma Pontes for their
clinical support. MMB was supported by Fundacao de Amparo a Pesquisa do
Estado de Sao Paulo (grant number 2009/11805-4). JASC (1B), AWZ (1C),
JECH (1D) and AEN (1A) are the recipients of a CNPq (Brazil) fellowship
award.
NR 40
TC 7
Z9 7
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-6222
EI 1099-1077
J9 HUM PSYCHOPHARM CLIN
JI Hum. Psychopharmacol.-Clin. Exp.
PD JAN
PY 2014
VL 29
IS 1
BP 94
EP 99
DI 10.1002/hup.2374
PG 6
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry;
Psychology
GA AA0OW
UT WOS:000330795700014
PM 24424711
ER
PT J
AU Schneider, G
Bowser, MJ
Shin, DM
Barr, FG
Ratajczak, MZ
AF Schneider, Gabriela
Bowser, Mark J.
Shin, Dong-Myung
Barr, Frederic G.
Ratajczak, Mariusz Z.
TI The paternally imprinted DLK1-GTL2 locus is differentially methylated in
embryonal and alveolar rhabdomyosarcomas
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE rhabdomyosarcoma; DLK1-GTL2 locus; genomic imprinting
ID CHILDRENS ONCOLOGY GROUP; DNA METHYLATION; STEM-CELLS; REGION;
EXPRESSION; GENE; DLK1; H19; MECHANISMS
AB Parental imprinting of differentially methylated regions (DMRs) contributes to appropriate expression of several developmentally important genes from paternally or maternally derived chromosomes. Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and is associated with altered expression of certain parentally imprinted genes. As previously reported, RMS cells display loss of imprinting (LOI) of the DMR at the IGF2-H19 locus, resulting in insulin-like growth factor 2 (IGF2) transcription from both paternally and maternally inherited chromosomes, and overall IGF2 overexpression. As the DLK1-GTL2 locus is structurally similar to the IGF2-H19 locus, the status of parental imprinting of the DLK1-GTL2 locus was studied in RMS. We observed that while both embryonal and alveolar rhabdomyosarcomas (ERMS and ARMS, respectively) show LOI of the DMR at the IGF2-H19 locus, imprinting of the DMR at the DLK1-GTL2 locus varies in association with the histological subtype of RMS. We found that, while ERMS tumors consistently show LOI of the DMR at the DLK1-GTL2 locus, ARMS tumors have erasure of imprinting (EOI) at this locus. These changes in imprinting status of the DLK1-GTL2 locus result in a higher GTL2/DLK1 mRNA ratio in ARMS as compared to ERMS. This difference in imprinting elucidates a novel genetic difference between these two RMS subtypes and may provide a potential diagnostic tool to distinguish between these subtypes.
C1 [Schneider, Gabriela; Shin, Dong-Myung; Ratajczak, Mariusz Z.] Univ Louisville, Stem Cell Inst, James Graham Brown Canc Ctr, Louisville, KY 40202 USA.
[Bowser, Mark J.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Barr, Frederic G.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Ratajczak, MZ (reprint author), Univ Louisville, Stem Cell Inst, James Graham Brown Canc Ctr, 500 S Floyd St,Rm 107, Louisville, KY 40202 USA.
EM g0schn01@louisville.edu; mzrata01@louisville.edu
RI Ratajczak, Mariusz Zdzislaw/N-1599-2014;
OI Schneider, Gabriela/0000-0003-2088-8695
FU NIH [2R01 DK074720, R01HL112788]; Stella and Henry Endowment
FX This study was supported by NIH grants 2R01 DK074720 and R01HL112788 and
the Stella and Henry Endowment to M.Z.R.
NR 25
TC 7
Z9 7
U1 0
U2 0
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD JAN
PY 2014
VL 44
IS 1
BP 295
EP 300
DI 10.3892/ijo.2013.2153
PG 6
WC Oncology
SC Oncology
GA AA0LI
UT WOS:000330786200032
PM 24173021
ER
PT J
AU Li, XL
Yang, JH
Rader, C
AF Li, Xiuling
Yang, Jiahui
Rader, Christoph
TI Antibody conjugation via one and two C-terminal selenocysteines
SO METHODS
LA English
DT Article
DE Antibody engineering; Antibody conjugation; Selenocysteine
ID GENETIC-CODE; DRUG
AB Conventional antibody conjugation methods generate antibody-drug conjugates that are heterogeneous mixtures with undefined stoichiometry and variable pharmacokinetic and pharmacodynamic properties. We have previously described a strategy to generate site-specific antibody conjugates by genetic engineering of an antibody with a single C-terminal selenocysteine, the 21st natural amino acid, which displays unique chemical reactivity allowing selective conjugation in the presence of all other natural amino acids. In the present work, we describe a method for expanding this technology to higher drug-to-antibody ratios by genetically engineering an antibody with two C-terminal selenocysteines. Both selenocysteines effectively conjugate to a fluorescent iodoacetamide derivative and the resulting conjugate fully retains its antigen binding capability. Our method provides a platform for creating stoichiometrically defined antibody-drug conjugates for therapeutic intervention. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Li, Xiuling; Rader, Christoph] Scripps Florida, Scripps Res Inst, Dept Canc Biol, Jupiter, FL 33458 USA.
[Yang, Jiahui; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rader, Christoph] Scripps Florida, Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
RP Rader, C (reprint author), Scripps Florida, Scripps Res Inst, Dept Canc Biol & Mol Therapeut, 130 Scripps Way 2C1, Jupiter, FL 33458 USA.
EM crader@scripps.edu
FU Intramural NIH HHS [ZIA BC010647-08, ZIA BC010648-08]
NR 17
TC 19
Z9 20
U1 0
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD JAN 1
PY 2014
VL 65
IS 1
BP 133
EP 138
DI 10.1016/j.ymeth.2013.05.023
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 302LM
UT WOS:000330606000015
PM 23756202
ER
PT J
AU Galpern, WR
Coffey, CS
Albanese, A
Cheung, K
Comella, CL
Ecklund, DJ
Fahn, S
Jankovic, J
Kieburtz, K
Lang, AE
McDermott, MP
Shefner, JM
Teller, JK
Thompson, JLP
Yeatts, SD
Jinnah, HA
AF Galpern, Wendy R.
Coffey, Christopher S.
Albanese, Alberto
Cheung, Ken
Comella, Cynthia L.
Ecklund, Dixie J.
Fahn, Stanley
Jankovic, Joseph
Kieburtz, Karl
Lang, Anthony E.
McDermott, Michael P.
Shefner, Jeremy M.
Teller, Jan K.
Thompson, John L. P.
Yeatts, Sharon D.
Jinnah, H. A.
TI Designing Clinical Trials for Dystonia
SO NEUROTHERAPEUTICS
LA English
DT Review
DE Dystonia; Clinical trials; Exploratory trials; Confirmatory trials;
Adaptive designs
ID DEEP-BRAIN-STIMULATION; CONTINUAL REASSESSMENT METHOD; EARLY
PARKINSON-DISEASE; CERVICAL DYSTONIA; BOTULINUM-TOXIN; DOUBLE-BLIND;
MOVEMENT-DISORDERS; TORSION DYSTONIA; RATING-SCALES; ONSET
AB With advances in the understanding of the pathophysiology of dystonia, novel therapeutics are being developed. Such therapies will require clinical investigation ranging from exploratory studies to examine safety, tolerability, dosage selection, and preliminary efficacy to confirmatory studies to evaluate efficacy definitively. As dystonia is a rare and complex disorder with clinical and etiological heterogeneity, clinical trials will require careful consideration of the trial design, including enrollment criteria, concomitant medication use, and outcome measures. Given the complexities of designing and implementing efficient clinical trials, it is important for clinicians and statisticians to collaborate closely throughout the clinical development process and that each has a basic understanding of both the clinical and statistical issues that must be addressed. To facilitate designing appropriate clinical trials in this field, we review important general clinical trial and regulatory principles, and discuss the critical components of trials with an emphasis on considerations specific to dystonia. Additionally, we discuss designs used in early exploratory, late exploratory, and confirmatory phases, including adaptive designs.
C1 [Galpern, Wendy R.] NINDS, NIH, Bethesda, MD 20892 USA.
[Coffey, Christopher S.; Ecklund, Dixie J.] Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
[Albanese, Alberto] Catholic Univ, Dept Neurol, Milan, Italy.
[Albanese, Alberto] Ist Nazl Neurol Carlo Besta, Milan, Italy.
[Cheung, Ken; Thompson, John L. P.] Columbia Univ, Dept Biostat, New York, NY USA.
[Comella, Cynthia L.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Fahn, Stanley] Columbia Univ, Neurol Inst, Movement Disorder Div, New York, NY USA.
[Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA.
[Kieburtz, Karl] Univ Rochester, Med Ctr, Ctr Human Expt Therapeut, Rochester, NY 14642 USA.
[Lang, Anthony E.] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Clin, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada.
[McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA.
[McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
[Shefner, Jeremy M.] Upstate Med Univ, Dept Neurol, Syracuse, NY USA.
[Teller, Jan K.] Dystonia Med Res Fdn, Chicago, IL USA.
[Yeatts, Sharon D.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Jinnah, H. A.] Emory Univ, Dept Neurol Human Genet & Pediat, Atlanta, GA 30322 USA.
RP Galpern, WR (reprint author), NINDS, NIH, 6001 Execut Blvd,Rm 2225, Bethesda, MD 20892 USA.
EM galpernw@ninds.nih.gov
FU Dystonia Medical Research Foundation; Dystonia Coalition from NINDS [U54
NS65701]; Office of Rare Diseases Research in NCATS at NIH; National
Institute of Neurological Disorders and Stroke [U13NS079084]
FX This article was based, in part, on a workshop that was held in May 2012
involving an international group of dystonia clinicians, clinical
trialists, and statisticians, as well as representatives from industry
and the US Food and Drug Administration. The workshop was sponsored by
the Dystonia Medical Research Foundation, The Dystonia Coalition (U54
NS65701 from NINDS and the Office of Rare Diseases Research in NCATS at
NIH), and the National Institute of Neurological Disorders and Stroke
(U13NS079084). Full conflict of interest disclosures are available in
the electronic supplementary material for this article.
NR 64
TC 8
Z9 8
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1933-7213
EI 1878-7479
J9 NEUROTHERAPEUTICS
JI Neurotherapeutics
PD JAN
PY 2014
VL 11
IS 1
BP 117
EP 127
DI 10.1007/s13311-013-0221-6
PG 11
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 302TC
UT WOS:000330626800013
PM 24282121
ER
PT J
AU Roschewski, M
Manasanch, EE
Wilson, WH
AF Roschewski, Mark
Manasanch, Elisabet E.
Wilson, Wyndham H.
TI Management of Heavy Chain Diseases: The Challenges of Biologic
Heterogeneity COMMENTARY ON THE BIANCHI ET AL ARTICLE: M. ROSCHEWSKI, EE
MANASANCH, WH WILSON
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID MYD88; MUTATION; MACROGLOBULINEMIA; LYMPHOMAS; PROTEIN; CELLS
C1 [Roschewski, Mark; Manasanch, Elisabet E.; Wilson, Wyndham H.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roschewski, M (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 16
TC 0
Z9 0
U1 0
U2 0
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD JAN
PY 2014
VL 28
IS 1
BP 63
EP 65
PG 3
WC Oncology
SC Oncology
GA 301QQ
UT WOS:000330547400008
PM 24683720
ER
PT J
AU Morris, SE
Rumsey, JM
Cuthbert, BN
AF Morris, Sarah E.
Rumsey, Judith M.
Cuthbert, Bruce N.
TI Rethinking mental disorders: The role of learning and brain plasticity
SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE
LA English
DT Article
DE Psychiatric diagnosis; RDoC; neuroplasticity; psychiatric treatment
ID TRANSCRANIAL MAGNETIC STIMULATION; OBSESSIVE-COMPULSIVE DISORDER;
TREATMENT-RESISTANT DEPRESSION; ANTERIOR CINGULATE CORTEX; GLUCOSE
METABOLIC-RATE; NEURAL STEM-CELL; REAL-TIME FMRI; PSYCHIATRIC-DISORDERS;
AUDITORY HALLUCINATIONS; COGNITIVE REMEDIATION
AB Recent research in neurodevelopment, neuroplasticity and genetics is providing new insights into the etiogenesis of psychopathology, but progress in treatment development has been hampered by reliance on diagnostic categories that are characterized by heterogeneity and based primarily on phenomenology. The NIMH Research Domain Criteria (RDoC) initiative seeks to provide a neuroscience-based nosological framework for future research on psychopathology, categorizing individuals for research purposes using a dimensional approach that capitalizes on advances in modern neuroscience. These scientific advances and new approaches to classification can inform the development of novel, circuit-based interventions and the personalization of treatment. In this paper, we review key advances areas in clinical neuroscience, describe the RDoC project and highlight some emerging treatment approaches that are consistent with these developments.
C1 [Morris, Sarah E.; Rumsey, Judith M.; Cuthbert, Bruce N.] NIMH, Div Adult Translat Res, Bethesda, MD 20892 USA.
RP Morris, SE (reprint author), NIMH, Div Adult Translat Res, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM sarah.morris@nih.gov
NR 144
TC 10
Z9 10
U1 2
U2 16
PU IOS PRESS
PI AMSTERDAM
PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS
SN 0922-6028
EI 1878-3627
J9 RESTOR NEUROL NEUROS
JI Restor. Neurol. Neurosci.
PY 2014
VL 32
IS 1
BP 5
EP 23
DI 10.3233/RNN-139015
PG 19
WC Neurosciences
SC Neurosciences & Neurology
GA 302FQ
UT WOS:000330588100002
PM 23902986
ER
PT J
AU Ahrens, K
Silver, R
Perkins, N
Wong, LC
Galai, N
Lesher, L
Faraggi, D
Wactawski-Wende, J
Townsend, J
Lynch, A
Mumford, S
Schisterman, E
AF Ahrens, Katherine
Silver, Robert
Perkins, Neil
Wong, Luchin
Galai, Noya
Lesher, Laurie
Faraggi, David
Wactawski-Wende, Jean
Townsend, Janet
Lynch, Anne
Mumford, Sunni
Schisterman, Enrique
TI Preconception low dose aspirin and preterm birth: findings from the
EAGeR (Effects of Aspirin in Gestation and Reproduction) randomized
trial
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Ahrens, Katherine; Perkins, Neil; Mumford, Sunni; Schisterman, Enrique] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Silver, Robert; Wong, Luchin; Lesher, Laurie] Univ Utah Hlth Serv, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Galai, Noya; Faraggi, David] Univ Haifa, Dept Stat, IL-31999 Haifa, Israel.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Townsend, Janet] Commonwealth Med Coll, Dept Family Community & Rural Hlth, Scranton, PA USA.
[Lynch, Anne] Univ Colorado, Dept Obstet & Gynecol, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S8
EP S8
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600013
ER
PT J
AU Bailit, J
AF Bailit, Jennifer
TI Induction for nonmedical indications compared with expectant management
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Bailit, Jennifer] Eunice Kennedy Shriver NICHD MFMU Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S280
EP S280
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600569
ER
PT J
AU Clark, EAS
AF Clark, Erin A. S.
TI Genetic predisposition to adverse neurodevelopmental outcome after early
preterm birth: a validation analysis
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Clark, Erin A. S.] Eunice Kennedy Shriver NICHD, Maternal Fetal Med Units, Bethesda, MD USA.
[Clark, Erin A. S.] Eunice Kennedy Shriver NICHD, Neonatal Res Networks, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S10
EP S10
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600018
ER
PT J
AU Clark-Ganheart, C
Reddy, U
Kominiarek, M
Huang, CC
Landy, H
Laughon, SK
AF Clark-Ganheart, Cecily
Reddy, Uma
Kominiarek, Michelle
Huang, Chun-Chih
Landy, Helain
Laughon, S. Katherine
TI The optimal delivery approach for obese women
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Clark-Ganheart, Cecily] Medstar Washington Hosp Ctr, Washington, DC USA.
[Reddy, Uma; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Kominiarek, Michelle] Univ Illinois, Chicago, IL USA.
[Landy, Helain] Medstar Georgetown Univ Hosp, Washington, DC USA.
[Huang, Chun-Chih] Medstar Hlth Res Inst, Hyattsville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S325
EP S325
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600663
ER
PT J
AU Costantine, M
AF Costantine, Maged
TI The effect of mode of delivery on childhood obesity
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Costantine, Maged] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S73
EP S74
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600123
ER
PT J
AU Downes, K
Hinkle, S
Sjaarda, L
Albert, P
Laughon, SK
AF Downes, Katheryne
Hinkle, Stefanie
Sjaarda, Lindsey
Albert, Paul
Laughon, S. Katherine
TI Prelabor and intrapartum cesarean delivery and subsequent risk of
placenta previa
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Downes, Katheryne; Hinkle, Stefanie; Sjaarda, Lindsey; Albert, Paul; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S263
EP S263
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600536
ER
PT J
AU Facco, F
Reid, K
Grobman, W
Parker, C
Zee, P
AF Facco, Francesca
Reid, Kathryn
Grobman, William
Parker, Corette
Zee, Phyllis
CA Natl Inst Child Hlth Human Dev
TI Sleep duration and continuity in nulliparous women
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Facco, Francesca] Univ Pittsburgh, Pittsburgh, PA USA.
[Reid, Kathryn; Grobman, William; Zee, Phyllis] Northwestern Univ, Chicago, IL 60611 USA.
[Parker, Corette] RTI Int, Res Triangle Pk, NC USA.
[Natl Inst Child Hlth Human Dev] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S361
EP S362
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600738
ER
PT J
AU Frascoli, M
MacKenzie, T
Coniglio, L
Gomez-Lopez, N
Romero, R
AF Frascoli, Michela
MacKenzie, Tippi
Coniglio, Lacy
Gomez-Lopez, Nardhy
Romero, Roberto
TI Activation of the fetal but not maternal adaptive immune system in
preterm premature rupture of membranes (PPROM)
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Frascoli, Michela; MacKenzie, Tippi; Coniglio, Lacy] UCSF, Eli & Edythe Broad Ctr Regenerat Med, San Francisco, CA USA.
[Frascoli, Michela; MacKenzie, Tippi; Coniglio, Lacy] UCSF, Fetal Treatment Ctr, San Francisco, CA USA.
[Gomez-Lopez, Nardhy; Romero, Roberto] NICHD, Perinatol Res Branch, Intramural Div, NIH,DHHS, Detroit, MI USA.
[Gomez-Lopez, Nardhy; Romero, Roberto] Hutzel Womens Hosp, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S361
EP S361
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600737
ER
PT J
AU Grobman, W
AF Grobman, William
TI Prediction of spontaneous preterm birth among nulliparous women with a
short cervix
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S358
EP S358
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600732
ER
PT J
AU Landon, M
AF Landon, Mark
TI Mild gestational diabetes mellitus (GDM) treatment and long term child
health
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Landon, Mark] Eunice Kennedy Shriver NICHD MFMU Networks, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S408
EP S409
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600836
ER
PT J
AU Lucas, JC
Dugan, EK
Aggarwal, V
Bale, S
Frayna, A
Hussong, M
Jobanputra, V
Richard, G
Vincent, L
Williams, B
Meck, J
Wapner, R
Levy, B
AF Lucas, Jaclyn Coletta
Dugan, Elizabeth Kramer
Aggarwal, Vimla
Bale, Sherri
Frayna, Aileen
Hussong, Melanie
Jobanputra, Vaidehi
Richard, Gabi
Vincent, Lisa
Williams, Bradley
Meck, Jeanne
Wapner, Ronald
Levy, Brynn
CA Prenatal Array Study Grp
TI Increased nuchal translucency and normal karyotype: value of additional
testing
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Lucas, Jaclyn Coletta; Aggarwal, Vimla; Jobanputra, Vaidehi; Wapner, Ronald; Levy, Brynn] Columbia Univ, Med Ctr, New York, NY USA.
[Dugan, Elizabeth Kramer; Bale, Sherri; Frayna, Aileen; Hussong, Melanie; Richard, Gabi; Vincent, Lisa; Williams, Bradley; Meck, Jeanne] GeneDx, Prenatal Diagnost Serv, Gaithersburg, MD USA.
[Prenatal Array Study Grp] NICHD, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S87
EP S87
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600151
ER
PT J
AU Romero, S
Geiersbach, K
Paxton, C
Presson, A
Schisterman, E
Branch, DW
Silver, R
AF Romero, Stephanie
Geiersbach, Katherine
Paxton, Christian
Presson, Angela
Schisterman, Enrique
Branch, D. Ware
Silver, Robert
TI Genetic abnormalities in early pregnancy loss
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Romero, Stephanie; Presson, Angela; Silver, Robert] Univ Utah, Salt Lake City, UT USA.
[Branch, D. Ware] Intermt Med Ctr, Murray, UT USA.
[Schisterman, Enrique] NICHD, Bethesda, MD USA.
[Geiersbach, Katherine; Paxton, Christian] ARUP Labs, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S78
EP S79
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600133
ER
PT J
AU Romero, S
Geiersbach, K
Paxton, C
Schisterman, E
Presson, A
Branch, DW
Silver, R
AF Romero, Stephanie
Geiersbach, Katherine
Paxton, Christian
Schisterman, Enrique
Presson, Angela
Branch, D. Ware
Silver, Robert
TI Chromosomal microarray analysis (CMA) vs karyotype in the evaluation of
early pregnancy loss
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Romero, Stephanie; Presson, Angela; Silver, Robert] Univ Utah, Salt Lake City, UT USA.
[Branch, D. Ware] Intermt Med Ctr, Murray, UT USA.
[Geiersbach, Katherine; Paxton, Christian] ARUP Labs, Salt Lake City, UT USA.
[Schisterman, Enrique] NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S79
EP S79
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600134
ER
PT J
AU Saade, G
AF Saade, George
TI Using pattern-recognition software to evaluate intrapartum fetal heart
(FHR) tracings
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Saade, George] Eunice Kennedy Shriver NICHD MFMU Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S290
EP S290
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600589
ER
PT J
AU Saade, G
AF Saade, George
TI Intra-amniotic sludge and adverse pregnancy outcomes in nulliparous
women with a short cervix
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Saade, George] Eunice Kennedy Shriver NICHD, MFMU Network, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S54
EP S54
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600084
ER
PT J
AU Silver, R
AF Silver, Robert
CA Stillbirth Collaborative Res
TI Exploration of microbial nucleic acids in stillbirth
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Silver, Robert] Univ Utah, Salt Lake City, UT USA.
[Stillbirth Collaborative Res] NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S201
EP S201
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600397
ER
PT J
AU Wong, LC
Schliep, K
Schisterman, E
Wactawski-Wende, J
Townsend, J
Lynch, A
Galai, N
Faraggi, D
Perkins, N
Mumford, S
Ye, AJ
Silver, R
AF Wong, Luchin
Schliep, Karen
Schisterman, Enrique
Wactawski-Wende, Jean
Townsend, Janet
Lynch, Anne
Galai, Noya
Faraggi, David
Perkins, Neil
Mumford, Sunni
Ye, Aijun
Silver, Robert
TI The effect of very short interpregnancy interval on pregnancy outcomes
after previous pregnancy loss
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Wong, Luchin; Silver, Robert] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Schliep, Karen; Schisterman, Enrique; Perkins, Neil; Mumford, Sunni; Ye, Aijun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Townsend, Janet] Commonwealth Med Coll, Dept Family Community & Rural Hlth, Scranton, PA USA.
[Lynch, Anne] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
[Galai, Noya; Faraggi, David] Univ Haifa, Dept Stat, IL-31999 Haifa, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S208
EP S209
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600413
ER
PT J
AU Yeung, E
Liu, AY
Mills, J
Zhang, CL
Mannisto, T
Boghossian, N
Robledo, C
Mendola, P
AF Yeung, Edwina
Liu, Aiyi
Mills, James
Zhang, Cuilin
Maennistoe, Tuija
Boghossian, Nansi
Robledo, Candace
Mendola, Pauline
TI Copeptin levels are elevated in women prior to diagnosis of clinical
pre-eclampsia
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Yeung, Edwina; Liu, Aiyi; Mills, James; Zhang, Cuilin; Maennistoe, Tuija; Boghossian, Nansi; Robledo, Candace; Mendola, Pauline] NICHD, Div Intramural Populat Hlth Res, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S146
EP S146
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600277
ER
PT J
AU Zhang, CL
Sundaram, R
Maisog, J
Barr, D
Louis, GB
AF Zhang, Cuilin
Sundaram, Rajeshwari
Maisog, Jose
Barr, Dana
Louis, Germaine Buck
TI Pre-gravid serum concentrations of perfluorooctanoic acid and the risk
of gestational diabetes: a prospective study in the LIFE study
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Zhang, Cuilin; Sundaram, Rajeshwari; Maisog, Jose; Louis, Germaine Buck] NICHD, NIH, Div Intramural Populat Hlth Res, Rockville, MD USA.
[Barr, Dana] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S145
EP S146
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600276
ER
PT J
AU Zhang, CL
Martin, K
Bowers, K
Liu, AY
Bao, W
Vaag, A
Yeung, E
Sun, LP
Boghossian, N
Hu, F
Olsen, S
AF Zhang, Cuilin
Martin, Kelly
Bowers, Katherine
Liu, Aiyi
Bao, Wei
Vaag, Allan
Yeung, Edwina
Sun, Liping
Boghossian, Nansi
Hu, Frank
Olsen, Sjurdur
TI Fasting glucose levels during pregnancy and long-term childhood growth
in the offspring
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Meeting Abstract
CT 34th Annual Scientific Pregnancy Meeting of the
Society-for-Maternal-Fetal-Medicine
CY FEB 03-08, 2014
CL New Orleans, LA
SP Soc Maternal Fetal Med
C1 [Zhang, Cuilin; Martin, Kelly; Bowers, Katherine; Liu, Aiyi; Bao, Wei; Yeung, Edwina; Sun, Liping; Boghossian, Nansi] NICHD, NIH, Div Intramural Populat Hlth Res, Rockville, MD USA.
[Vaag, Allan] Danish Natl State Hosp, Copenhagen, Denmark.
[Olsen, Sjurdur] Statens Serum Inst, Ctr Fetal Programming, DK-2300 Copenhagen, Denmark.
[Hu, Frank] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Hu, Frank] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RI Bowers, Katherine/N-5226-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
SU S
BP S44
EP S44
PG 1
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 298KK
UT WOS:000330322600070
ER
PT J
AU Desrosiers, NA
Lee, D
Scheidweiler, KB
Concheiro-Guisan, M
Gorelick, DA
Huestis, MA
AF Desrosiers, Nathalie A.
Lee, Dayong
Scheidweiler, Karl B.
Concheiro-Guisan, Marta
Gorelick, David A.
Huestis, Marilyn A.
TI In vitro stability of free and glucuronidated cannabinoids in urine
following controlled smoked cannabis
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Cannabinoids; Urine; Stability; Glucuronide
ID TANDEM MASS-SPECTROMETRY; ACID; DRUGS; TEMPERATURES; METABOLISM;
SPECIMENS; THCCOOH; SAMPLES; PLASMA; BLOOD
AB Analyte stability is an important factor in urine test interpretation, yet cannabinoid stability data are limited. A comprehensive study of Delta(9)-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol, cannabinol, THC-glucuronide, and THCCOOH-glucuronide stabilities in authentic urine was completed. Urine samples after ad libitum cannabis smoking were pooled to prepare low and high pools for each study participant; baseline concentrations were measured within 24 h at room temperature (RT), 4 A degrees C and -20 A degrees C. Stability at RT, 4 A degrees C and -20 A degrees C was evaluated by Friedman tests for up to 1 year. THCCOOH, THC-glucuronide, and THCCOOH-glucuronide were quantified in baseline pools. RT THCCOOH baseline concentrations were significantly higher than -20 A degrees C, but not 4 A degrees C baseline concentrations. After 1 week at RT, THCCOOH increased, THCCOOH-glucuronide decreased, but THC-glucuronide was unchanged. In RT low pool, total THCCOOH (THCCOOH + THCCOOH-glucuronide) was significantly lower after 1 week. At 4 A degrees C, THCCOOH was stable 2 weeks, THCCOOH-glucuronide 1 month and THC-glucuronide for at least 6 months. THCCOOH was stable frozen for 1 year, but 6 months high pool results were significantly higher than baseline; THC-glucuronide and THCCOOH-glucuronide were stable for 6 months. Total THCCOOH was stable 6 months at 4 A degrees C, and frozen 6 months (low) and 1 year (high). THC, cannabidiol and cannabinol were never detected in urine; although not detected initially, 11-OH-THC was detected in 2 low and 3 high pools after 1 week at RT. Substantial THCCOOH-glucuronide deconjugation was observed at RT and 4 A degrees C. Analysis should be conducted within 3 months if non-hydrolyzed THCCOOH or THCCOOH-glucuronide quantification is required.
C1 [Desrosiers, Nathalie A.; Lee, Dayong; Scheidweiler, Karl B.; Concheiro-Guisan, Marta; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Desrosiers, Nathalie A.; Lee, Dayong] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200 Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse, NIH
FX We acknowledge the contributions of the clinical staffs of the National
Institute on Drug Abuse, Intramural Research Program, and Behavioral
Pharmacology Research Unit and Clinical Research Unit, Johns Hopkins
Bayview Medical Center, as well as Dr. David M. Schwope for protocol
assistance, Dan Nichols and the staff at the Forensic Toxicology Drug
Testing Laboratory in Fort Meade who provided urine creatinine data, the
Graduate Partnership Program, NIH and the "Fondation Baxter et Alma
Ricard". This research was funded by the Intramural Research Program,
National Institute on Drug Abuse, NIH.
NR 29
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PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JAN
PY 2014
VL 406
IS 3
BP 785
EP 792
DI 10.1007/s00216-013-7524-7
PG 8
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 288QD
UT WOS:000329625800013
PM 24292435
ER
PT J
AU Fu, D
Arias, IM
AF Fu, Dong
Arias, Irwin M.
TI Intracellular trafficking of P-glycoprotein (vol 44, pg 461, 2012)
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Correction
C1 [Fu, Dong; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Cell Biol & Metab Program, Bethesda, MD 20892 USA.
RP Fu, D (reprint author), NICHD, NIH, Bldg 18T,Room 101,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fudong@mail.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
EI 1878-5875
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD JAN
PY 2014
VL 46
BP 161
EP 161
DI 10.1016/j.biocel.2013.10.011
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 301QI
UT WOS:000330546600017
ER
PT J
AU Chen, MY
Bandettini, WP
Shanbhag, SM
Vasu, S
Booker, OJ
Leung, SW
Wilson, JR
Kellman, P
Hsu, LY
Lederman, RJ
Arai, AE
AF Chen, Marcus Y.
Bandettini, W. Patricia
Shanbhag, Sujata M.
Vasu, Sujethra
Booker, Oscar J.
Leung, Steve W.
Wilson, Joel R.
Kellman, Peter
Hsu, Li-Yueh
Lederman, Robert J.
Arai, Andrew E.
TI Concordance and diagnostic accuracy of vasodilator stress cardiac MRI
and 320-detector row coronary CTA
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Coronary artery disease; Cardiac magnetic resonance imaging; Cardiac
computed tomography; Myocardial perfusion imaging
ID CARDIOVASCULAR MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY ANGIOGRAPHY;
ARTERY-DISEASE; METAANALYSIS; RADIATION; INTERVENTION; ADENOSINE;
OBESITY; TRIAL
AB Vasodilator stress cardiac magnetic resonance (CMR) detects ischemia whereas coronary CT angiography (CTA) detects atherosclerosis. The purpose of this study was to determine concordance and accuracy of vasodilator stress CMR and coronary CTA in the same subjects. We studied 151 consecutive subjects referred to detect or exclude suspected obstructive coronary artery disease (CAD) in patients without known disease or recurrent stenosis or ischemia in patients with previously treated CAD. Vasodilator stress CMR was performed on a 1.5 T scanner. CTA was performed on a 320-detector row system. Subjects were followed for cardiovascular events and downstream diagnostic testing. Subjects averaged 56 +/- A 12 years (60 % male), and 62 % had intermediate pre-test probability for obstructive CAD. Follow-up averaged 450 +/- A 115 days and was 100 % complete. CMR and CTA agreed in 92 % of cases (kappa 0.81, p < 0.001). The event-free survival was 97 % for non-ischemic and 39 % for ischemic CMR (p < 0.0001). The event-free survival was 99 % for non-obstructive and 36 % for obstructive CTA (p < 0.0001). Using a reference standard including quantitative invasive angiography or major cardiovascular events, CMR and CTA had respective sensitivities of 93 and 98 %; specificities of 96 and 96 %; positive predictive values of 91 and 91 %; negative predictive values of 97 and 99 %; and accuracies of 95 and 97 %. Non-ischemic vasodilator stress CMR or non-obstructive coronary CTA were highly concordant and each confer an excellent prognosis. CMR and CTA are both accurate for assessment of obstructive CAD in a predominantly intermediate risk population.
C1 [Chen, Marcus Y.; Bandettini, W. Patricia; Shanbhag, Sujata M.; Vasu, Sujethra; Booker, Oscar J.; Leung, Steve W.; Wilson, Joel R.; Kellman, Peter; Hsu, Li-Yueh; Lederman, Robert J.; Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging Lab, Div Intramural Res, US Dept HHS,Cardiovasc & Pulm Branch,NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Adv Cardiovasc Imaging Lab, Div Intramural Res, US Dept HHS,Cardiovasc & Pulm Branch,NIH, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM araia@nih.gov
RI Leung, Steve/E-5624-2011;
OI Leung, Steve/0000-0003-2832-2258; lederman, robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health, USA [ZIA HL004607-15, ZIA
HL006137-03, ZIA HL006138-03]
FX This work was funded by the Division of Intramural Research, National
Heart, Lung, and Blood Institute, National Institutes of Health, USA
(ZIA HL004607-15, ZIA HL006137-03, ZIA HL006138-03). The authors thank
Gregory Henderson RT, Dennis Johnson RT, Christine Mancini RT, Shirley
Rollison RT, Pamela Vincent RT, Marsha Block RN, Kathie Bronson CRNP,
Jennifer Henry RN, Tracy Lowrey RN and Luis Rosario for expert help with
imaging, patient care, and follow-up of study participants.
NR 29
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U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
EI 1573-0743
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD JAN
PY 2014
VL 30
IS 1
BP 109
EP 119
DI 10.1007/s10554-013-0300-0
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 298RT
UT WOS:000330342800012
PM 24122452
ER
PT J
AU Vickers, KC
Remaley, AT
AF Vickers, Kasey C.
Remaley, Alan T.
TI Thematic Review Series: High Density Lipoprotein Structure, Function,
and Metabolism HDL and cholesterol: life after the divorce?
SO JOURNAL OF LIPID RESEARCH
LA English
DT Review
DE microRNA; extracellular miRNA; small RNA carrier
ID APOLIPOPROTEIN-A-I; FATTY-ACID ESTERS; RECEPTOR CLASS-B; ACUTE CORONARY
SYNDROME; ALPHA-TOCOPHEROL; SCAVENGER RECEPTOR; BILE-ACIDS; SPHINGOSINE
1-PHOSPHATE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL-CELLS
AB For decades, HDL and HDL-cholesterol (HDL-C) levels were viewed as synonymous, and modulation of HDL-C levels by drug therapy held great promise for the prevention and treatment of cardiovascular disease. Nevertheless, recent failures of drugs that raise HDL-C to reduce cardiovascular risk and the now greater understanding of the complexity of HDL composition and biology have prompted researchers in the field to redefine HDL. As such, the focus of HDL has now started to shift away from a cholesterol-centric view toward HDL particle number, subclasses, and other alternative metrics of HDL. Many of the recently discovered functions of HDL are, in fact, not strictly conferred by its ability to promote cholesterol flux but by the other molecules it transports, including a diverse set of proteins, small RNAs, hormones, carotenoids, vitamins, and bioactive lipids. Based on HDL's ability to interact with almost all cells and transport and deliver fat-soluble cargo, HDL has the remarkable capacity to affect a wide variety of endocrine-like systems. In this review, we characterize HDL's unique cargo and address the functional relevance and consequences of HDL transport and delivery of noncholesterol molecules to recipient cells and tissues.
C1 [Vickers, Kasey C.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Vickers, KC (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
EM kasey.c.vickers@vanderbilt.edu
FU National Institutes of Health [K22-HL-113039-01]; Intramural Research
Program
FX This work was supported by National Institutes of Health Grant
K22-HL-113039-01 (K.C.V.) and the Intramural Research Program (A.T.R.).
NR 95
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U1 0
U2 29
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD JAN
PY 2014
VL 55
IS 1
BP 4
EP 12
DI 10.1194/jlr.R035964
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 301LZ
UT WOS:000330535100002
PM 23515282
ER
PT J
AU Freeman, SR
Jin, XT
Anzinger, JJ
Xu, Q
Purushothaman, S
Fessler, MB
Addadi, L
Kruth, HS
AF Freeman, Sebastian R.
Jin, Xueting
Anzinger, Joshua J.
Xu, Qing
Purushothaman, Sonya
Fessler, Michael B.
Addadi, Lia
Kruth, Howard S.
TI ABCG1-mediated generation of extracellular cholesterol microdomains
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE atherosclerosis; apolipoprotein A-I; high density lipoprotein; probucol;
macrophages
ID LOW-DENSITY-LIPOPROTEIN; BINDING CASSETTE-TRANSPORTER;
APOLIPOPROTEIN-A-I; MONOCYTE-DERIVED MACROPHAGES; MEMBRANE-LIPID
DOMAINS; SCAVENGER RECEPTOR BI; NIEMANN-PICK-DISEASE; CELLULAR
CHOLESTEROL; PLASMA-MEMBRANE; ANTIBODY RECOGNITION
AB Previous studies have demonstrated that the ATP-binding cassette transporters (ABC)A1 and ABCG1 function in many aspects of cholesterol efflux from macrophages. In this current study, we continued our investigation of extracellular cholesterol microdomains that form during enrichment of macrophages with cholesterol. Human monocyte-derived macrophages and mouse bone marrow-derived macrophages, differentiated with macrophage colony-stimulating factor (M-CSF) or granulocyte macrophage colony-stimulation factor (GM-CSF), were incubated with acetylated LDL (AcLDL) to allow for cholesterol enrichment and processing. We utilized an anti-cholesterol microdomain monoclonal antibody to reveal pools of unesterified cholesterol, which were found both in the extracellular matrix and associated with the cell surface, that we show function in reverse cholesterol transport. Coincubation of AcLDL with 50 mu g/ml apoA-I eliminated all extracellular and cell surface-associated cholesterol microdomains, while coincubation with the same concentration of HDL only removed extracellular matrix-associated cholesterol microdomains. Only at an HDL concentration of 200 mu g/ml did HDL eliminate the cholesterol microdomains that were cell-surface associated. The deposition of cholesterol microdomains was inhibited by probucol, but it was increased by the liver X receptor (LXR) agonist TO901317, which upregulates ABCA1 and ABCG1. Extracellular cholesterol microdomains did not develop when ABCG1-deficient mouse bone marrow-derived macrophages were enriched with cholesterol. Our findings show that generation of extracellular cholesterol microdomains is mediated by ABCG1 and that reverse cholesterol transport occurs not only at the cell surface but also within the extracellular space.
C1 [Freeman, Sebastian R.; Jin, Xueting; Anzinger, Joshua J.; Xu, Qing; Purushothaman, Sonya; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA.
[Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Addadi, Lia] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel.
RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kruthh@nhlbi.nih.gov
FU Intramural Research Program, National Heart, Lung, and Blood Institute,
National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Heart, Lung, and Blood Institute, National Institutes of Health.
NR 57
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U1 1
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD JAN
PY 2014
VL 55
IS 1
BP 115
EP 127
DI 10.1194/jlr.M044552
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 301LZ
UT WOS:000330535100012
PM 24212237
ER
PT J
AU Whitt, J
Shipley, SM
Newman, DJ
Zuck, KM
AF Whitt, James
Shipley, Suzanne M.
Newman, David J.
Zuck, Karina M.
TI Tetramic Acid Analogues Produced by Coculture of Saccharopolyspora
erythraea with Fusarium pallidoroseum
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID TRICHODERMA-HARZIANUM; SECONDARY METABOLITES; EQUISETI NRRL-5537; FUNGAL
METABOLITES; TOXIN EQUISETIN; GENOME SEQUENCE; INHIBITORS; DERIVATIVES;
INTEGRASE; INDUCTION
AB Coculture of the fungus Fusarium pallidoroseum with the bacterium Saccharopolyspora erythraea was found to produce three new decalin-type tetramic acid analogues related to equisetin. The structures were determined by spectroscopic methods. The absolute configurations were established by circular dichroism spectroscopy and comparing the data with those of equisetin.
C1 [Whitt, James; Shipley, Suzanne M.; Zuck, Karina M.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Newman, David J.] NCI, Nat Prod Branch, Dev Therapeut Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Zuck, KM (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, POB B, Frederick, MD 21702 USA.
EM zuckk@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Developmental Therapeutics Program in the Division
of Cancer Treatment and Diagnosis of the National Cancer Institute
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 no. 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 Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute. We gratefully acknowledge T. DeLloyd for
assistance with fermentations, Q. Van and A. Castro Ruiz for running NMR
experiments, S. Tarasov and M. Dyba (Structural Biophysics Laboratory)
for assistance with the CD determinations, and L. Cartner for help
running the polarimeter.
NR 37
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U1 1
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD JAN
PY 2014
VL 77
IS 1
BP 173
EP 177
DI 10.1021/np400761g
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 298PN
UT WOS:000330336800027
PM 24422636
ER
PT J
AU Ziegler, A
Wilson, AF
Gagnon, F
AF Ziegler, A.
Wilson, A. F.
Gagnon, F.
TI Informatics and Genetic Epidemiology
SO METHODS OF INFORMATION IN MEDICINE
LA English
DT Editorial Material
C1 [Ziegler, A.] Med Univ Lubeck, Inst Med Biometry & Stat, Univ Med Ctr Schleswig Holstein, D-23562 Lubeck, Germany.
[Ziegler, A.] Med Univ Lubeck, Ctr Clin Trials, D-23562 Lubeck, Germany.
[Wilson, A. F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, Baltimore, MD USA.
[Gagnon, F.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
RP Ziegler, A (reprint author), Med Univ Lubeck, Inst Med Biometry & Stat, Univ Med Ctr Schleswig Holstein, Campus Lubeck Ratzeburger Allee 160 House 24, D-23562 Lubeck, Germany.
EM ziegler@imbs.uni-luebeck.de
NR 4
TC 0
Z9 0
U1 0
U2 4
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 2014
VL 53
IS 1
BP 1
EP 2
PG 2
WC Computer Science, Information Systems; Health Care Sciences & Services;
Medical Informatics
SC Computer Science; Health Care Sciences & Services; Medical Informatics
GA 299SG
UT WOS:000330415400001
PM 24407729
ER
PT J
AU Gaidamakov, S
Maximova, OA
Chon, H
Blewett, NH
Wang, HS
Crawford, AK
Day, A
Tulchin, N
Crouch, RJ
Morse, HC
Blitzer, RD
Maraia, RJ
AF Gaidamakov, Sergei
Maximova, Olga A.
Chon, Hyongi
Blewett, Nathan H.
Wang, Hongsheng
Crawford, Amanda K.
Day, Amanda
Tulchin, Natalie
Crouch, Robert J.
Morse, Herbert C., III
Blitzer, Robert D.
Maraia, Richard J.
TI Targeted Deletion of the Gene Encoding the La Autoantigen (Sjogren's
Syndrome Antigen B) in B Cells or the Frontal Brain Causes Extensive
Tissue Loss
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TRANSFER-RNA MATURATION; POLYMERASE-III TRANSCRIPTS; PRECURSOR
TRANSFER-RNAS; BINDING PROTEIN LA; NASCENT RNA; MOUSE-BRAIN; LEADER RNA;
IN-VITRO; SCHIZOSACCHAROMYCES-POMBE; SMALL RIBONUCLEOPROTEINS
AB La antigen (Sjogren's syndrome antigen B) is a phosphoprotein associated with nascent precursor tRNAs and other RNAs, and it is targeted by autoantibodies in patients with Sjogren's syndrome, systemic lupus erythematosus, and neonatal lupus. Increased levels of La are associated with leukemias and other cancers, and various viruses usurp La to promote their replication. Yeast cells (Saccharomyces cerevisiae and Schizosaccharomyces pombe) genetically depleted of La grow and proliferate, whereas deletion from mice causes early embryonic lethality, raising the question of whether La is required by mammalian cells generally or only to surpass a developmental stage. We developed a conditional La allele and used it in mice that express Cre recombinase in either B cell progenitors or the forebrain. B cell Mb1(Cre) La-deleted mice produce no B cells. Consistent with alpha CamKII Cre, which induces deletion in hippocampal CA1 cells in the third postnatal week and later throughout the neocortex, brains develop normally in La-deleted mice until similar to 5 weeks and then lose a large amount of forebrain cells and mass, with evidence of altered pretRNA processing. The data indicate that La is required not only in proliferating cells but also in nondividing postmitotic cells. Thus, La is essential in different cell types and required for normal development of various tissue types.
C1 [Gaidamakov, Sergei; Chon, Hyongi; Blewett, Nathan H.; Crawford, Amanda K.; Day, Amanda; Crouch, Robert J.; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Programs, NIH, Bethesda, MD USA.
[Maximova, Olga A.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Hongsheng; Morse, Herbert C., III] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Tulchin, Natalie] Mt Sinai Sch Med, Dept Pathol, New York, NY USA.
[Blitzer, Robert D.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Washington, DC USA.
RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Programs, NIH, Bethesda, MD USA.
EM maraiar@mail.nih.gov
OI Morse, Herbert/0000-0002-9331-3705
FU Intramural Research Programs of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Allergy and Infectious
Diseases.
NR 63
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Z9 3
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JAN
PY 2014
VL 34
IS 1
BP 123
EP 131
DI 10.1128/MCB.01010-13
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 302DK
UT WOS:000330581600010
PM 24190965
ER
PT J
AU Blanco, FF
Sanduja, S
Deane, NG
Blackshear, PJ
Dixon, DA
AF Blanco, Fernando F.
Sanduja, Sandhya
Deane, Natasha G.
Blackshear, Perry J.
Dixon, Dan A.
TI Transforming Growth Factor beta Regulates P-Body Formation through
Induction of the mRNA Decay Factor Tristetraprolin
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID N-TERMINAL KINASE; INTESTINAL EPITHELIAL-CELLS; AU-RICH ELEMENTS;
TGF-BETA; PROCESSING BODIES; POSTTRANSCRIPTIONAL REGULATION; PROTEIN
TRISTETRAPROLIN; MICRORNA MATURATION; COLORECTAL-CANCER; STRESS GRANULES
AB Transforming growth factor beta (TGF-beta) is a potent growth regulator and tumor suppressor in normal intestinal epithelium. Likewise, epithelial cell growth is controlled by rapid decay of growth-related mRNAs mediated through 3= untranslated region (UTR) AU-rich element (ARE) motifs. We demonstrate that treatment of nontransformed intestinal epithelial cells with TGF-beta inhibited ARE-mRNA expression. This effect of TGF-beta was promoted through increased assembly of cytoplasmic RNA processing (P) bodies where ARE-mRNA localization was observed. P-body formation was dependent on TGF-beta /Smad signaling, as Smad3 deletion abrogated P-body formation. In concert with increased P-body formation, TGF-beta induced expression of the ARE-binding protein tristetraprolin (TTP), which colocalized to P bodies. TTP expression was necessary for TGF-beta -dependent P-body formation and promoted growth inhibition by TGF-beta. The significance of this was observed in vivo, where colonic epithelium deficient in TGF-beta /Smad signaling or TTP expression showed attenuated P-body levels. These results provide new insight into TGF-beta's antiproliferative properties and identify TGF-beta as a novel mRNA stability regulator in intestinal epithelium through its ability to promote TTP expression and subsequent P-body formation.
C1 [Blanco, Fernando F.; Dixon, Dan A.] Univ Kansas, Med Ctr, Dept Canc Biol, Kansas City, KS 66103 USA.
[Sanduja, Sandhya] Whitehead Inst Biomed Sci, Cambridge, MA USA.
[Deane, Natasha G.] Vanderbilt Univ, Med Ctr, Dept Surg, Nashville, TN USA.
[Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Dixon, DA (reprint author), Univ Kansas, Med Ctr, Dept Canc Biol, Kansas City, KS 66103 USA.
EM ddixon3@kumc.edu
FU National Institutes of Health [R01CA134609]; American Cancer Society
[RSG-06-122-01-CNE]
FX This work was supported by the National Institutes of Health
(R01CA134609) and the American Cancer Society (RSG-06-122-01-CNE).
NR 79
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U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JAN
PY 2014
VL 34
IS 2
BP 180
EP 195
DI 10.1128/MCB.01020-13
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 302DM
UT WOS:000330581800003
PM 24190969
ER
PT J
AU Eccleston, JL
Koh, C
Markello, TC
Gahl, WA
Heller, T
AF Eccleston, Jason L.
Koh, Christopher
Markello, Thomas C.
Gahl, William A.
Heller, Theo
TI \ An apparent homozygous deletion in maltase-glucoamylase, a lesson in
the evolution of SNP arrays (vol 107, pg 674, 2012)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Correction
C1 [Eccleston, Jason L.; Koh, Christopher; Heller, Theo] Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD USA.
[Markello, Thomas C.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Markello, Thomas C.; Gahl, William A.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
[Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
RP Gahl, WA (reprint author), NIH, Off Clin Director, Res Inst, Bldg 10,Room 10C103,10 Ctr,MSC 1851, Bethesda, MD 20892 USA.
EM Bgahl@helix.nih.gov; TheoH@intra.niddk.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2014
VL 111
IS 1
BP 58
EP 59
DI 10.1016/j.ymgme.2013.11.008
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 296AS
UT WOS:000330158100010
ER
PT J
AU Benazzi, C
Al-Dissi, A
Chau, CH
Figg, WD
Sarli, G
de Oliveira, JT
Gartner, F
AF Benazzi, C.
Al-Dissi, A.
Chau, C. H.
Figg, W. D.
Sarli, G.
de Oliveira, J. T.
Gaertner, F.
TI Angiogenesis in Spontaneous Tumors and Implications for Comparative
Tumor Biology
SO SCIENTIFIC WORLD JOURNAL
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMAS;
VASCULAR-PERMEABILITY FACTOR; CANCER STEM-CELLS; INTUSSUSCEPTIVE
MICROVASCULAR GROWTH; METASTATIC COLORECTAL-CANCER; MAMMARY-GLAND
TUMORS; BREAST-CANCER; ANTIANGIOGENIC THERAPY; FACTOR EXPRESSION
AB Blood supply is essential for development and growth of tumors and angiogenesis is the fundamental process of new blood vessel formation from preexisting ones. Angiogenesis is a prognostic indicator for a variety of tumors, and it coincides with increased shedding of neoplastic cells into the circulation and metastasis. Several molecules such as cell surface receptors, growth factors, and enzymes are involved in this process. While antiangiogenic therapy for cancer has been proposed over 20 years ago, it has garnered much controversy in recent years within the scientific community. The complex relationships between the angiogenic signaling cascade and antiangiogenic substances have indicated the angiogenic pathway as a valid target for anticancer drug development and VEGF has become the primary antiangiogenic drug target. This review discusses the basic and clinical perspectives of angiogenesis highlighting the importance of comparative biology in understanding tumor angiogenesis and the integration of these model systems for future drug development.
C1 [Benazzi, C.; Sarli, G.] Univ Bologna, Dept Vet Med Sci, I-40064 Bologna, Italy.
[Al-Dissi, A.] Univ Saskatchewan, Western Coll Vet Med, Dept Vet Pathol, Saskatoon, SK S7N 5B4, Canada.
[Chau, C. H.; Figg, W. D.] NCI, Bethesda, MD 20892 USA.
[de Oliveira, J. T.; Gaertner, F.] Univ Porto IPATIMUP, Inst Pathol & Mol Immunol, P-4200456 Oporto, Portugal.
[de Oliveira, J. T.; Gaertner, F.] Univ Porto ICBAS UP, Abel Salazar Inst Biomed Sci, P-4200456 Oporto, Portugal.
RP Sarli, G (reprint author), Univ Bologna, Dept Vet Med Sci, Via Tolara 50, I-40064 Bologna, Italy.
EM giuseppe.sarli@unibo.it
RI Figg Sr, William/M-2411-2016
NR 165
TC 6
Z9 9
U1 1
U2 14
PU HINDAWI LTD
PI LONDON
PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND
SN 1537-744X
J9 SCI WORLD J
JI Sci. World J.
PY 2014
AR 919570
DI 10.1155/2014/919570
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AA0CN
UT WOS:000330762800001
ER
PT J
AU Minniti, CP
Delaney, KMH
Gorbach, AM
Xu, DH
Lee, CCR
Malik, N
Koroulakis, A
Antalek, M
Maivelett, J
Peters-Lawrence, M
Novelli, EM
Lanzkron, SM
Axelrod, KC
Kato, GJ
AF Minniti, Caterina P.
Delaney, Kara-Marie H.
Gorbach, Alexander M.
Xu, Dihua
Lee, Chyi-Chia Richard
Malik, Nitin
Koroulakis, Antony
Antalek, Matthew
Maivelett, Jordan
Peters-Lawrence, Marlene
Novelli, Enrico M.
Lanzkron, Sophie M.
Axelrod, Karen C.
Kato, Gregory J.
TI Vasculopathy, inflammation, and blood flow in leg ulcers of patients
with sickle cell anemia
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID CHRONIC VENOUS INCOMPETENCE; PULMONARY-HYPERTENSION;
LACTATE-DEHYDROGENASE; RISK-FACTOR; DISEASE; ULCERATION; SPHEROCYTOSIS;
THALASSEMIA; WOUNDS; DEATH
AB Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population. Am. J. Heamtol. 89:1-6, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Minniti, Caterina P.; Delaney, Kara-Marie H.; Peters-Lawrence, Marlene; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Gorbach, Alexander M.; Malik, Nitin; Koroulakis, Antony; Antalek, Matthew; Maivelett, Jordan] NIBIB, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD USA.
[Xu, Dihua] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Novelli, Enrico M.] Div Hematol Oncol, Pittsburgh, PA USA.
[Lanzkron, Sophie M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA.
[Axelrod, Karen C.] NIH, Nursing & Patient Care Serv, Bethesda, MD 20892 USA.
RP Minniti, CP (reprint author), NHLBI, Hematol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM minnitic@nhlbi.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Division of Intramural Research, National Heart, Lung and Blood
Institute [1 ZIA HL006127-01, 1 ZIA HL006162-01]
FX Contract grant sponsor: Division of Intramural Research, National Heart,
Lung and Blood Institute; Contract grant numbers: 1 ZIA HL006127-01, 1
ZIA HL006162-01.
NR 44
TC 11
Z9 11
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JAN
PY 2014
VL 89
IS 1
BP 1
EP 6
DI 10.1002/ajh.23571
PG 6
WC Hematology
SC Hematology
GA 295CJ
UT WOS:000330093900001
PM 23963836
ER
PT J
AU Hudson, JL
Kendall, PC
Chu, BC
Gosch, E
Martin, E
Taylor, A
Knight, A
AF Hudson, Jennifer L.
Kendall, Philip C.
Chu, Brian C.
Gosch, Elizabeth
Martin, Erin
Taylor, Alan
Knight, Ashleigh
TI Child involvement, alliance, and therapist flexibility: Process
variables in cognitive-behavioural therapy for anxiety disorders in
childhood
SO BEHAVIOUR RESEARCH AND THERAPY
LA English
DT Article
DE Therapy process; Alliance; Child involvement; Flexibility; Child anxiety
ID RANDOMIZED CLINICAL-TRIAL; INTERVIEW SCHEDULE; ADOLESCENT THERAPY;
WORKING ALLIANCE; MANIFEST ANXIETY; MISSING DATA; YOUTH; PREDICTION;
SCALE; CARE
AB Background: This study examined the relations between treatment process variables and child anxiety outcomes. Method: Independent raters watched/listened to taped therapy sessions of 151 anxiety-disordered (6-14 yr-old; M = 10.71) children (43% boys) and assessed process variables (child alliance, therapist alliance, child involvement, therapist flexibility and therapist functionality) within a manual-based cognitive-behavioural treatment. Latent growth modelling examined three latent variables (intercept, slope, and quadratic) for each process variable. Child age, gender, family income and ethnicity were examined as potential antecedents. Outcome was analyzed using factorially derived clinician, mother, father, child and teacher scores from questionnaire and structured diagnostic interviews at pretreatment, posttreatment and 12-month follow-up. Results: Latent growth models demonstrated a concave quadratic curve for child involvement and therapist flexibility over time. A predominantly linear, downward slope was observed for alliance, and functional flexibility remained consistent over time. Increased alliance, child involvement and therapist flexibility showed some albeit inconsistent, associations with positive treatment outcome. Conclusion: Findings support the notion that maintaining the initial high level of alliance or involvement is important for clinical improvement. There is some support that progressively increasing alliance/involvement also positively impacts on treatment outcome. These findings were not consistent across outcome measurement points or reporters. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Hudson, Jennifer L.; Taylor, Alan; Knight, Ashleigh] Macquarie Univ, Ctr Emot Hlth, Dept Psychol, N Ryde, NSW 2109, Australia.
[Kendall, Philip C.] Temple Univ, Philadelphia, PA 19122 USA.
[Chu, Brian C.] Rutgers State Univ, Piscataway, NJ 08855 USA.
[Gosch, Elizabeth] Philadelphia Coll Osteopath Med, Philadelphia, PA USA.
[Martin, Erin] NIMH, Bethesda, MD USA.
RP Hudson, JL (reprint author), Macquarie Univ, Ctr Emot Hlth, Dept Psychol, N Ryde, NSW 2109, Australia.
EM jennie.hudson@mq.edu.au
OI Hudson, Jennie/0000-0001-5778-2670
FU NIMH NIH HHS [R01 MH064484]
NR 41
TC 3
Z9 3
U1 0
U2 31
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0005-7967
EI 1873-622X
J9 BEHAV RES THER
JI Behav. Res. Ther.
PD JAN
PY 2014
VL 52
BP 1
EP 8
DI 10.1016/j.brat.2013.09.011
PG 8
WC Psychology, Clinical
SC Psychology
GA 295YK
UT WOS:000330152100001
PM 24246476
ER
PT J
AU Metzger, MB
Pruneda, JN
Klevit, RE
Weissman, AM
AF Metzger, Meredith B.
Pruneda, Jonathan N.
Klevit, Rachel E.
Weissman, Allan M.
TI RING-type E3 ligases: Master manipulators of E2 ubiquitin-conjugating
enzymes and ubiquitination
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE RING finger; U-box; Ubiquitin ligase (E3); Ubiquitin-conjugating enzyme
(E2); Protein degradation; Catalysis
ID GROWTH-FACTOR RECEPTOR; RETICULUM-ASSOCIATED DEGRADATION; FANCONI-ANEMIA
PATHWAY; MATRIX PROTEIN IMPORT; NUCLEAR-PORE COMPLEX; END RULE PATHWAY;
ENDOPLASMIC-RETICULUM; STRUCTURAL BASIS; C-CBL; CHAIN FORMATION
AB RING finger domain and RING finger-like ubiquitin ligases (E3s), such as U-box proteins, constitute the vast majority of known E3s. RING-type E3s function together with ubiquitin-conjugating enzymes (E2s) to mediate ubiquitination and are implicated in numerous cellular processes. In part because of their importance in human physiology and disease, these proteins and their cellular functions represent an intense area of study. Here we review recent advances in RING-type E3 recognition of substrates, their cellular regulation, and their varied architecture. Additionally, recent structural insights into RING-type E3 function, with a focus on important interactions with E2s and ubiquitin, are reviewed. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf. Published by Elsevier B.V.
C1 [Metzger, Meredith B.; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
[Pruneda, Jonathan N.; Klevit, Rachel E.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
RP Klevit, RE (reprint author), Univ Washington, Dept Biochem, Box 357350, Seattle, WA 98195 USA.
EM klevit@uw.edu; weissmaa@mail.nih.gov
FU National Institute of General Medical Sciences [R01 GM088055, R01
GM098503]; National Institutes of Health, National Cancer Institute,
Center for Cancer Research
FX The study of RING-type E3s continues to grow extremely rapidly. We
regret that it was possible to only cite a fraction of the outstanding
primary publications in this field. This work was supported by the
National Institute of General Medical Sciences grants R01 GM088055 and
R01 GM098503 (R.E.K.) and by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (A.M.W.).
NR 170
TC 85
Z9 86
U1 10
U2 37
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JAN
PY 2014
VL 1843
IS 1
SI SI
BP 47
EP 60
DI 10.1016/j.bbamcr.2013.05.026
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 294AG
UT WOS:000330014200006
PM 23747565
ER
PT J
AU Gao, R
Das, BB
Chatterjee, R
Abaan, OD
Agama, K
Matuo, R
Vinson, C
Meltzer, PS
Pommier, Y
AF Gao, Rui
Das, Benu Brata
Chatterjee, Raghunath
Abaan, Ogan D.
Agama, Keli
Matuo, Renata
Vinson, Charles
Meltzer, Paul S.
Pommier, Yves
TI Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1
(TDP1) in human lung cancer cells from the NCI-60 panel
SO DNA REPAIR
LA English
DT Article
DE TDP1; Topoisomerases; Topotecan; CellMiner; Promoter hypermethylation
ID STRAND BREAK REPAIR; TOPOISOMERASE-I; SPINOCEREBELLAR ATAXIA; COVALENT
COMPLEXES; CLEAVAGE COMPLEXES; AXONAL NEUROPATHY; DAMAGE; EXPRESSION;
ENZYME; PHARMACOLOGY
AB Tyrosyl-DNA-phosphodiesterase 1 (TDP1) repairs 3'-blocking DNA lesions by catalytically hydrolyzing the tyrosyl-DNA-phosphodiester bond of trapped topoisomerase I (Top1) cleavage complexes (Topl cc). It also removes 3'-blocking residues derived from oxidative damage or incorporation of chain terminating anticancer and antiviral nucleosides. Thus, TDP1 is regarded as a determinant of resistance to Top1 inhibitors and chain terminating nucleosides, and possibly of genomic stability. In the 60 cell lines of the NCI Developmental Therapeutic Anticancer Screen (the NCI-60), whose whole genome transcriptome and mutations have recently been characterized, we discovered two human lung cancer cell lines deficient for TDP1 (NCI_H522 and HOP_62). HOP_62 shows undetectable TDP1 mRNA and NCI_H522 bears a homozygous deleterious mutation of TDP1 at a highly conserved amino acid residue (K292E). Absence of TDP1 protein and lack of TDP1 catalytic activity were demonstrated in cell lysates from both cell lines. Lack of TDP1 expression in HOP_62 was shown to be due to TDP1 promoter hypermethylation. Our study provides insights into the possible inactivation of TDP1 in cancers and its relationship to cellular response to Top1-targeted drugs. It also reveals two TDP1 knockout lung cancer cell lines for further TDP1 functional analyses. Published by Elsevier B.V.
C1 [Gao, Rui; Das, Benu Brata; Agama, Keli; Matuo, Renata; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Abaan, Ogan D.; Meltzer, Paul S.] NCI, Mol Genet Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chatterjee, Raghunath; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM pommier@mail.nih.gov
FU Intramural NIH HHS [Z01 BC006150-26]
NR 45
TC 6
Z9 6
U1 3
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD JAN
PY 2014
VL 13
BP 1
EP 9
DI 10.1016/j.dnarep.2013.09.001
PG 9
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 298OU
UT WOS:000330334700001
PM 24355542
ER
PT J
AU Sharma, NK
Lebedeva, M
Thomas, T
Kovalenko, OA
Stumpf, JD
Shadel, GS
Santos, JH
AF Sharma, Nilesh K.
Lebedeva, Maria
Thomas, Terace
Kovalenko, Olga A.
Stumpf, Jeffrey D.
Shadel, Gerald S.
Santos, Janine H.
TI Intrinsic mitochondrial DNA repair defects in Ataxia Telangiectasia
SO DNA REPAIR
LA English
DT Article
DE ATM; Mitochondria; Mitochondrial DNA repair; DNA ligase 3; Ataxia
Telangiectasia
ID BASE EXCISION-REPAIR; OXIDATIVE STRESS; LIGASE-III; RIBONUCLEOTIDE
REDUCTASE; PROTEIN-KINASE; STRAND BREAKS; ATM; CELLS; REPLICATION;
DYSFUNCTION
AB Ataxia Telangiectasia (A-T) is a progressive childhood disorder characterized most notably by cerebellar degeneration and predisposition to cancer. A-T is caused by mutations in the kinase ATM, a master regulator of the DNA double-strand break response. In addition to DNA-damage signaling defects, A-T cells display mitochondrial dysfunction that is thought to contribute to A-T pathogenesis. However, the molecular mechanism leading to mitochondrial dysfunction in A-T remains unclear. Here, we show that lack of ATM leads to reduced mitochondrial DNA (mtDNA) integrity and mitochondrial dysfunction, which are associated to defective mtDNA repair. While protein levels of mtDNA repair proteins are essentially normal, in the absence of ATM levels specifically of DNA ligase III (Lig3), the only DNA ligase working in mitochondria is reduced. The reduction of Lig3 is observed in different A-T patient cells, in brain and pre-B cells derived from ATM knockout mice as well as upon transient or stable knockdown of ATM. Furthermore, pharmacological inhibition of Lig3 in wild type cells phenocopies the mtDNA repair defects observed in A-T patient cells. As targeted deletion of LIG3 in the central nervous system causes debilitating ataxia in mice, reduced Lig3 protein levels and the consequent mtDNA repair defect may contribute to A-T neurodegeneration. A-T is thus the first disease characterized by diminished Lig3. Published by Elsevier B.V.
C1 [Sharma, Nilesh K.; Thomas, Terace; Kovalenko, Olga A.; Santos, Janine H.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Physiol & Pharmacol, Newark, NJ 07103 USA.
[Lebedeva, Maria; Shadel, Gerald S.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA.
[Shadel, Gerald S.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Stumpf, Jeffrey D.] NIEHS, Mol Genet Lab, Durham, NC 27709 USA.
RP Santos, JH (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Durham, NC 27709 USA.
EM Janine.santos@nih.gov
OI Sharma, Nilesh Kumar/0000-0002-8774-3020
FU Department of Defense, Army Research Office [56027LS]; NIH [NS56206];
A-T Children's Project
FX This work was partially funded by the Department of Defense, Army
Research Office, Grant number 56027LS to J.H.S., and grants from the NIH
(NS56206) and the A-T Children's Project to G.S.S.
NR 45
TC 19
Z9 19
U1 2
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD JAN
PY 2014
VL 13
BP 22
EP 31
DI 10.1016/j.dnarep.2013.11.002
PG 10
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 298OU
UT WOS:000330334700003
PM 24342190
ER
PT J
AU Kirklin, JK
Naftel, DC
Kormos, RL
Pagani, FD
Myers, SL
Stevenson, LW
Acker, MA
Goldstein, DL
Silvestry, SC
Milano, CA
Baldwin, JT
Pinney, S
Rame, JE
Miller, MA
AF Kirklin, James K.
Naftel, David C.
Kormos, Robert L.
Pagani, Francis D.
Myers, Susan L.
Stevenson, Lynne W.
Acker, Michael. A.
Goldstein, Daniel. L.
Silvestry, Scott C.
Milano, Carmelo A.
Baldwin, J. Timothy
Pinney, Sean
Rame, J. Eduardo
Miller, Marissa A.
TI Interagency Registry for Mechanically Assisted Circulatory Support
(INTERMACS) analysis of pump thrombosis in the Heart Mate II left
ventricular assist device
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE INTERMACS; pump thrombosis; LVAD; HeartMate II; heart failure
ID DESTINATION THERAPY; DIAGNOSIS; ECHOCARDIOGRAPHY; FAILURE
AB BACKGROUND: Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database.
METHODS: Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis.
RESULTS: Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant.
CONCLUSIONS: Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HVBI LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.
C1 [Kirklin, James K.; Naftel, David C.; Myers, Susan L.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
[Kormos, Robert L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Pagani, Francis D.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Stevenson, Lynne W.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Acker, Michael. A.; Rame, J. Eduardo] Univ Penn, Philadelphia, PA 19104 USA.
[Goldstein, Daniel. L.] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Silvestry, Scott C.] Washington Univ, Sch Med, St Louis, MO USA.
[Milano, Carmelo A.] Duke Univ, Durham, NC USA.
[Baldwin, J. Timothy; Miller, Marissa A.] NHLBI, Bethesda, MD 20892 USA.
[Pinney, Sean] Mt Sinai Med Ctr, New York, NY 10029 USA.
RP Kirklin, JK (reprint author), Univ Alabama Birmingham, 760 THT, Birmingham, AL 35294 USA.
EM jkirklin@uab.edu
FU NHLBI [HHSN268201100025C]; Heart Ware
FX This analysis and the INTERMACS device database are funded by NHLBI
contract HHSN268201100025C. James K. Kirklin is the principal
investigator for INTERMACS.; David C. Naftel is a consultant for Heart
Ware, and Francis D. Pagani does contract research with Heart Ware,
managed by the University of Michigan.
NR 22
TC 133
Z9 133
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD JAN
PY 2014
VL 33
IS 1
BP 12
EP 22
DI 10.1016/j.healun.2013.11.001
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 297LA
UT WOS:000330255700002
PM 24418730
ER
PT J
AU Sirenko, S
Maltsev, VA
Maltseva, LA
Yang, DM
Lukyanenko, Y
Vinogradova, TM
Jones, LR
Lakatta, EG
AF Sirenko, Syevda
Maltsev, Victor A.
Maltseva, Larissa A.
Yang, Dongmei
Lukyanenko, Yevgeniya
Vinogradova, Tatiana M.
Jones, Larry R.
Lakatta, Edward G.
TI Sarcoplasmic reticulum Ca2+ cycling protein phosphorylation in a
physiologic Ca2+ milieu unleashes a high-power, rhythmic Ca2+ clock in
ventricular myocytes: Relevance to arrhythmias and bio-pacemaker design
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Cardiac ventricular myocytes; Calcium clock; Calcium cycling; Protein
phosphorylation; Spontaneous local calcium releases
ID CARDIAC RYANODINE RECEPTOR; PIG SINOATRIAL NODE; PKA PHOSPHORYLATION;
CALCIUM-RELEASE; MUSCLE SERCA2A; KINASE-II; CELLS; PHOSPHOLAMBAN;
OSCILLATIONS; CHANNEL
AB Basal phosphorylation of sarcoplasmic reticulum (SR) Ca2+ proteins is high in sinoatrial nodal cells (SANC), which generate partially synchronized, spontaneous, rhythmic, diastolic local Ca2+ releases (LCRs), but low in ventricular myocytes (VM), which exhibit rare diastolic, stochastic SR-generated Ca2+ sparks. We tested the hypothesis that in a physiologic Ca2+ milieu, and independent of increased Ca2+ influx, an increase in basal phosphorylation of SR Ca2+ cycling proteins will convert stochastic Ca2+ sparks into periodic, high-power Ca2+ signals of the type that drives SANC normal automaticity. We measured phosphorylation of SR-associated proteins, phospholamban (PLB) and ryanodine receptors (RyR), and spontaneous local Ca2+ release characteristics (LCR) in permeabilized single, rabbit VM in physiologic [Ca2+], prior to and during inhibition of protein phosphatase (PP) and phosphodiesterase (POE), or addition of exogenous cAMP, or in the presence of an antibody (2012), that specifically inhibits binding of the PLB to SERCA-2. In the absence of the aforementioned perturbations, VM could only generate stochastic local Ca2+ releases of low power and low amplitude, as assessed by confocal Ca2+ imaging and spectral analysis. When the kinetics of Ca2+ pumping into the SR were increased by an increase in PLB phosphoiylation (via POE and PP inhibition or addition of cAMP) or by 2012, self-organized, "clock-like" local Ca2+ releases, partially synchronized in space and time (Ca2+ wavelets), emerged, and the ensemble of these rhythmic local Ca2+ wavelets generated a periodic high-amplitude Ca2+ signal. Thus, a Ca2+ clock is not specific to pacemaker cells, but can also be unleashed in VM when SR Ca2+ cycling increases and spontaneous local Ca2+ release becomes partially synchronized. This unleashed Ca2+ clock that emerges in a physiological Ca2+ milieu in VM has two faces, however: it can provoke ventricular arrhythmias; or if harnessed, can be an important feature of novel bio-pacemaker designs. Published by Elsevier Ltd.
C1 [Sirenko, Syevda; Maltsev, Victor A.; Maltseva, Larissa A.; Yang, Dongmei; Lukyanenko, Yevgeniya; Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA.
[Jones, Larry R.] Indiana Univ, Sch Med, Krannert Inst Cardiol, Dept Med, Indianapolis, IN 46202 USA.
RP Lakatta, EG (reprint author), NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM LakattaE@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, Baltimore, Maryland; National Institutes of Health
[HL49428]
FX This work is supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, Baltimore,
Maryland, and, in part, by National Institutes of Health Grant HL49428
(Larry Jones).
NR 42
TC 6
Z9 6
U1 1
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD JAN
PY 2014
VL 66
BP 106
EP 115
DI 10.1016/j.yjmcc.2013.11.011
PG 10
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 294XH
UT WOS:000330080700011
PM 24274954
ER
PT J
AU Li, KG
Simons-Morton, BG
Brooks-Russell, A
Ehsani, J
Hingson, R
AF Li, Kaigang
Simons-Morton, Bruce G.
Brooks-Russell, Ashley
Ehsani, Johnathon
Hingson, Ralph
TI Drinking and Parenting Practices as Predictors of Impaired Driving
Behaviors Among US Adolescents
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID GROWTH CURVE ANALYSES; PROTECTIVE FACTORS; ABUSE PREVENTION; YOUNG
ADULTHOOD; RISK BEHAVIORS; SUBSTANCE USE; ALCOHOL-USE; DRUG-USE;
SMOKING; SCHOOL
AB Objective: The purpose of this study was to identify the extent to which 10th-grade substance use and parenting practices predicted 11th-grade teenage driving while alcohol-/other drug impaired (DWI) and riding with alcohol-/other drug impaired drivers (RWI). Method: The data were from Waves 1 and 2 of the NEXT Generation study, with longitudinal assessment of a nationally representative sample of 10th graders starting in 2009-2010. Multivariate logistic regression analysis was used to examine the prospective associations between proposed predictors (heavy episodic drinking, illicit drug use, parental monitoring knowledge and control) in Wave 1 and DWI/RWI. Results: Heavy episodic drinking at Wave 1 predicted Wave 2 DWI (odds ratio [OR] = 3.73, p < .001) and RWI (OR = 3.92, p < .001) after controlling for parenting practices and selected covariates. Father's monitoring knowledge predicted lower DWI prevalence at Wave 2 when controlling for covariates and teenage substance use (OR = 0.66, p < .001). In contrast, mother's monitoring knowledge predicted lower RWI prevalence at Wave 2 when controlling for covariates only (OR = 0.67, p < .05), but the effect was reduced to nonsignificance when controlling for teen substance use. Conclusions: Heavy episodic drinking predicted DWI and RWI. In addition, parental monitoring knowledge, particularly by fathers, was protective against DWI, independent of the effect of substance use. This suggests that the enhancement of parenting practices could potentially discourage adolescent DWI. The findings suggest that the parenting practices of fathers and mothers may have differential effects on adolescent impaired-driving behaviors.
C1 [Li, Kaigang; Simons-Morton, Bruce G.; Brooks-Russell, Ashley; Ehsani, Johnathon] NICHHD, Hlth Behav Branch, Bethesda, MD 20892 USA.
[Hingson, Ralph] NIAAA, Epidemiol & Prevent Res Div, Rockville, MD 20852 USA.
RP Li, KG (reprint author), NICHHD, Hlth Behav Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd 7B13B, Bethesda, MD 20892 USA.
EM kaigang.li@nih.gov
RI Brooks-Russell, Ashley/F-8364-2014;
OI Brooks-Russell, Ashley/0000-0002-7728-8423; Simons-Morton,
Bruce/0000-0003-1099-6617
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development [HHSN267200800009C];
National Heart, Lung and Blood Institute; National Institute on Alcohol
Abuse and Alcoholism; 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 (Contract no. HHSN267200800009C); the National Heart, Lung
and Blood Institute; the National Institute on Alcohol Abuse and
Alcoholism; and the Maternal and Child Health Bureau of the Health
Resources and Services Administration, with supplemental support from
the National Institute on Drug Abuse.
NR 56
TC 9
Z9 10
U1 4
U2 17
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
EI 1938-4114
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD JAN
PY 2014
VL 75
IS 1
BP 5
EP 15
PG 11
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 295UW
UT WOS:000330142800001
PM 24411792
ER
PT J
AU Hingson, R
White, A
AF Hingson, Ralph
White, Aaron
TI New Research Findings Since the 2007 Surgeon General's Call to Action to
Prevent and Reduce Underage Drinking: A Review
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Review
ID ADOLESCENT ALCOHOL-USE; RANDOMIZED CONTROLLED-TRIAL; PARENT-BASED
INTERVENTION; COLLEGE-STUDENT DRINKING; HIGH-RISK DRINKING; SUBSTANCE
USE; DRUG-USE; OUTLET DENSITY; USE DISORDERS; YOUNG-ADULTS
AB Objective: In 2007, the U.S. Department of Health and Human Services issued The Surgeon General's Call To Action To Prevent And Reduce Underage Drinking, a publication documenting a problem linked to nearly 5,000 injury deaths annually and poor academic performance, potential cognitive deficits, risky sexual behavior, physical and sexual assaults, and other substance use. This report reviews subsequent underage drinking and related traffic fatality trends and research on determinants, consequences, and prevention interventions. Method: New research reports, meta-analyses, and systematic literature reviews were examined. Results: Since the Call to Action, reductions in underage frequency of drinking, heavy drinking occasions, and alcohol-related traffic deaths that began in the 1980s when the drinking age nationally became 21 have continued. Knowledge regarding determinants and consequences, particularly the effects of early-onset drinking, parental alcohol provision, and cognitive effects, has expanded. Additional studies support associations between the legal drinking age of 21, zero tolerance laws, higher alcohol prices, and reduced drinking and related problems. New research suggests that use/lose laws, social host liability, internal possession laws, graduated licensing, and night driving restrictions reduce traffic deaths involving underage drinking drivers. Additional studies support the positive effects of individually oriented interventions, especially screening and brief motivational interventions, web and face-to-face social norms interventions, college web-based interventions, parental interventions, and multicomponent community interventions. Conclusions: Despite reductions in underage alcohol consumption and related traffic deaths, underage drinking remains an enduring problem. Continued research is warranted in minimally studied areas, such as prospective studies of alcohol and brain development, policy studies of use/lose laws, internal possession laws, social host liability, and parent family interventions.
C1 [Hingson, Ralph; White, Aaron] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
RP Hingson, R (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane, Bethesda, MD 20892 USA.
EM rhingson@mail.nih.gov
NR 98
TC 27
Z9 27
U1 7
U2 34
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
EI 1938-4114
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD JAN
PY 2014
VL 75
IS 1
BP 158
EP 169
PG 12
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 295UW
UT WOS:000330142800017
PM 24411808
ER
PT J
AU Denlinger, CS
Ligibel, J
AF Denlinger, Crystal S.
Ligibel, Jennifer
TI A Work in Progress: Developing the New NCCN Guidelines for Survivorship
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
ID CANCER SURVIVORS; CARE
C1 [Denlinger, Crystal S.] Fox Chase Canc Ctr, Philadelphia, PA USA.
[Ligibel, Jennifer] Dana Farber Canc Inst, Womens Canc Program, Boston, MA USA.
[Ligibel, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Ligibel, Jennifer] NCI, Transdisciplinary Res Energet & Canc Initiat, Bethesda, MD 20892 USA.
NR 15
TC 1
Z9 1
U1 0
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JAN
PY 2014
VL 12
IS 1
BP 1
EP 4
PG 4
WC Oncology
SC Oncology
GA 298OG
UT WOS:000330333200001
PM 24453287
ER
PT J
AU Gawel, D
Fijalkowska, IJ
Jonczyk, P
Schaaper, RM
AF Gawel, Damian
Fijalkowska, Iwona J.
Jonczyk, Piotr
Schaaper, Roel M.
TI Effect of dNTP pool alterations on fidelity of leading and lagging
strand DNA replication in E. coli
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Article
DE DNA replication fidelity; Leading and lagging strands; Base.base
mispairs; dNTP precursors; Base selection; Exonucleolytic proofreading
ID NUCLEOSIDE DIPHOSPHATE KINASE; POLYMERASE III HOLOENZYME;
ESCHERICHIA-COLI; BASE SUBSTITUTION; MISMATCH REPAIR; MUTATOR; GENE;
MUTAGENESIS; CHROMOSOME; MUTATIONS
AB The fidelity with which organisms replicate their chromosomal DNA is of considerable interest. Detailed studies in the bacterium Escherichia coli have indicated that the fidelity of leading- and lagging-strand DNA replication is not the same, based on experiments in which the orientation of certain mutational targets on the chromosome was inverted relative to the movement of the replication fork: different mutation rates for several base-pair substitutions were observed depending on this orientation. While these experiments are indicative of differential replication fidelity in the two strands, a conclusion whether leading or lagging strand is the more accurate depends on knowledge of the primary mispairing error responsible for the base substitutions in question. A broad analysis of in vitro base-pairing preferences of DNA polymerases led us to propose that lagging-strand is the more accurate strand. In the present work, we present more direct in vivo evidence in support of this proposal. We determine the orientation dependence of mutant frequencies in ndk and dcd strains, which carry defined dNTP pool alterations. As these pool alterations lead to predictable effects on the array of possible mispairing errors, they mark the strands in which the observed errors occur. The combined results support the proposed higher accuracy of lagging-strand replication in E. coli. Published by Elsevier B.V.
C1 [Gawel, Damian; Fijalkowska, Iwona J.; Jonczyk, Piotr] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland.
[Gawel, Damian; Schaaper, Roel M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Gawel, D (reprint author), Med Ctr Postgrad Educ, Dept Biochem & Mol Biol, Ul Marymoncka 99, PL-02813 Warsaw, Poland.
EM gawel@cmkp.edu.pl
RI Fijalkowska, Iwona/I-7796-2016
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES065086]; Foundation for Polish
Science TEAM program [TEAM/2011-8/1]
FX We thank Drs. Jordan Saint-Charles and Kasia Maslowska of the NIEHS for
their careful reading of the manuscript for this paper. This work was
supported by project number Z01 ES065086 of the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences.
IJ.F. acknowledges support from project TEAM/2011-8/1 (New players
involved in the maintenance of genomic stability) from the Foundation
for Polish Science TEAM program.
NR 36
TC 5
Z9 5
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
EI 1873-135X
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD JAN
PY 2014
VL 759
BP 22
EP 28
DI 10.1016/j.mrfmmm.2013.11.003
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 297MM
UT WOS:000330259600004
PM 24269257
ER
PT J
AU Nie, LM
Chen, M
Sun, XL
Rong, PF
Zheng, NF
Chen, XY
AF Nie, Liming
Chen, Mei
Sun, Xiaolian
Rong, Pengfei
Zheng, Nanfeng
Chen, Xiaoyuan
TI Palladium nanosheets as highly stable and effective contrast agents for
in vivo photoacoustic molecular imaging
SO NANOSCALE
LA English
DT Article
ID GOLD NANOPARTICLES; TOMOGRAPHY; GENERATION; NANOCAGES; CANCER; SIZE; PD
AB A stable and efficient contrast agent is highly desirable for photoacoustic (PA) imaging applications. Recently gold nanostructures have been widely reported and studied for PA imaging and photothermal therapy. However, the structures of the nonspherical gold nanoparticles are easily destroyed after laser irradiation and thus may fail to complete the intended tasks. In this study, we propose to apply palladium nanosheets (PNSs), with strong optical absorption in the near-infrared (NIR) region, as a new class of exogenous PA contrast agents. PA and ultrasound (US) images were acquired sequentially by a portable and fast photoacoustic tomography (PAT) system with a hand-held transducer. Significant and long-lasting imaging enhancement in SCC7 head and neck squamous cell carcinoma was successfully observed in mice by PAT over time after tail vein administration of PNSs. The morphology and functional perfusion of the tumors were delineated in PA images due to the nanoparticle accumulation. PAT of the main organs was also conducted ex vivo to trace the fate of PNSs, which was further validated by inductively coupled plasma atomic emission spectrometry (ICP-AES). No obvious toxic effect was observed by in vitro MTT assay and ex vivo histological examination 7 days after PNS administration. With the combination of a portable imaging instrument and signal specificity, PNSs might be applied as stable and effective agents for photoacoustic cancer detection, diagnosis and treatment guidance.
C1 [Nie, Liming; Sun, Xiaolian; Rong, Pengfei; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Nie, Liming] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China.
[Chen, Mei; Zheng, Nanfeng] Xiamen Univ, Coll Chem & Chem Engn, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.
[Chen, Mei; Zheng, Nanfeng] Xiamen Univ, Coll Chem & Chem Engn, Dept Chem, Xiamen 361005, Peoples R China.
RP Zheng, NF (reprint author), Xiamen Univ, Coll Chem & Chem Engn, State Key Lab Phys Chem Solid Surfaces, Xiamen 361005, Peoples R China.
EM nfzheng@xmu.edu.cn; shawn.chen@nih.gov
RI 陈, 美/E-6081-2013; Zheng, Nanfeng/G-4613-2010; Nie, Liming/F-7718-2016
OI Zheng, Nanfeng/0000-0001-9879-4790;
FU National Science Foundation of China [81301257, 81371596]; National
Basic Research Program of China (973 program) [2013CB733802,
2014CB744503]; intramural research program of the National Institute of
Biomedical Imaging and Bioengineering
FX This project is supported in part by the National Science Foundation of
China (81301257, 81371596), the National Basic Research Program of China
(973 program 2013CB733802, 2014CB744503), and by the intramural research
program of the National Institute of Biomedical Imaging and
Bioengineering. We also thank summer intern Mr. Eshwar Manoharan for the
editorial assistance.
NR 26
TC 41
Z9 41
U1 11
U2 127
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-3364
EI 2040-3372
J9 NANOSCALE
JI Nanoscale
PY 2014
VL 6
IS 3
BP 1271
EP 1276
DI 10.1039/c3nr05468c
PG 6
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 294JK
UT WOS:000330041400004
PM 24317132
ER
PT J
AU Seth, RK
Das, S
Kumar, A
Chanda, A
Kadiiska, MB
Michelotti, G
Manautou, J
Diehl, AM
Chatterjee, S
AF Seth, Ratanesh Kumar
Das, Suvarthi
Kumar, Ashutosh
Chanda, Anindya
Kadiiska, Maria B.
Michelotti, Gregory
Manautou, Jose
Diehl, Anna Mae
Chatterjee, Saurabh
TI CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8+T
cells aid progression of environment-linked nonalcoholic steatohepatitis
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Bromodichloromethane; Lipid peroxidation; Apoptosis; CD3; Leptin; IL-2
ID FATTY LIVER-DISEASE; CD8(+) T-CELLS; EXTRACELLULAR-MATRIX; IMMUNE
MODULATION; OXIDATIVE STRESS; STELLATE CELLS; KUPFFER CELLS; ACTIVATION;
FIBROSIS; APOPTOSIS
AB Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression. To identify the relevant subsets of T-lymphocytes in CYP2E1-dependent, environment-linked NASH, we utilized a model of diet induced obese (DID) mice that are chronically exposed to bromodichloromethane. Mice deficient in CYP2E1, leptin (ob/ob mice), or both T and B cells (Pfp/Rag2 double knockout (1(0) mice) were used to delineate the role of each of these factors in metabolic oxidative stress-induced T cell activation. Results revealed that elevated levels of lipid peroxidation, tyrosyl radical formation, mitochondrial tyrosine nitration and hepatic leptin as a consequence of metabolic oxidative stress caused increased levels of hepatic CD57, a marker of peripheral blood lymphocytes including NKT cells. CD8 + CD57 + cytotoxic T cells but not CD4 + CD57 + cells were significantly decreased in mice lacking CYP2E1 and leptin. There was a significant increase in the levels of T cell cytokines IL-2, IL-1 beta, and IFN-gamma in bromodichloromethane exposed DID mice but not in mice that lacked CYP2E1, leptin or T and B cells. Apoptosis as evidenced by TUNEL assay and levels of cleaved caspase-3 was significantly lower in leptin and Pfp/Rag2 KO mice and highly correlated with protection from NASH. The results described above suggest that higher levels of oxidative stress-induced leptin mediated CD8 + CD57 + T cells play an important role in the development of NASH. It also provides a novel insight of immune dysregulation and may be a key biomarker in NASH. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Seth, Ratanesh Kumar; Das, Suvarthi; Chanda, Anindya; Chatterjee, Saurabh] Univ S Carolina, Arnold Sch Publ Hlth, Dept Environm Hlth Sci, Environm Hlth & Dis Lab, Columbia, SC 29208 USA.
[Kumar, Ashutosh; Kadiiska, Maria B.] NIEHS, Lab Toxicol & Pharmacol, Free Rad Metab Grp, Res Triangle Pk, NC 27709 USA.
[Michelotti, Gregory; Diehl, Anna Mae] Duke Univ, Div Gastroenterol, Durham, NC 27707 USA.
[Manautou, Jose] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA.
RP Chatterjee, S (reprint author), Univ S Carolina, Dept Environm Hlth Sci, Environm Hlth & Dis Lab, Columbia, SC 29208 USA.
EM schatt@mailbox.sc.edu
RI Seth, Ratanesh/M-3700-2016;
OI Seth, Ratanesh/0000-0002-7078-0052
FU NIH [4R00ES019875-02, R01DK053792]; Intramural Research Program of the
National Institutes of Health; National Institute of Environmental
Health Sciences
FX The authors gratefully acknowledge the technical services of Benny
Davidson at the IRF, University of South Carolina, School of Medicine.
We also thank Dr David C. Volz for the use of the BX51 fluorescence
microscope and the Instrumentation Resource Facility (IRF) at the
University of South Carolina School of Medicine for equipment usage and
consulting services. This work has been supported by NIH pathway to
Independence Award (4R00ES019875-02 to Saurabh Chatterjee), NIH R01
(R01DK053792 to Anna Mae Diehl) and the Intramural Research Program of
the National Institutes of Health and the National Institute of
Environmental Health Sciences.
NR 49
TC 11
Z9 12
U1 0
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JAN 1
PY 2014
VL 274
IS 1
BP 42
EP 54
DI 10.1016/j.taap.2013.10.029
PG 13
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 297LD
UT WOS:000330256000006
PM 24211274
ER
PT J
AU Stanley, RE
Ragusa, MJ
Hurley, JH
AF Stanley, Robin E.
Ragusa, Michael J.
Hurley, James H.
TI The beginning of the end: how scaffolds nucleate autophagosome
biogenesis
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
DE SNAREs; Atg1; Atg9; Atg13; autophagy; ULK1; membrane bending; vesicle
tethering
ID PROTEIN-KINASE COMPLEX; SACCHAROMYCES-CEREVISIAE; ATG1 KINASE;
PREAUTOPHAGOSOMAL STRUCTURE; SELECTIVE AUTOPHAGY; TRAPP COMPLEXES;
MEMBRANE-FUSION; EARLY STEPS; TRS85; MACROAUTOPHAGY
AB Autophagy is a conserved mechanism that is essential for cell survival in starvation. Moreover, autophagy maintains cellular health by clearing unneeded or harmful materials from cells. Autophagy proceeds by the engulfment of bulk cytosol and organelles by a cup-shaped double-membrane sheet known as the phagophore. The phagophore closes on itself to form the autophagosome, which delivers its contents to the vacuole or lysosome for degradation. A multiprotein complex comprising the protein kinase autophagy-related protein 1 (Atg1) together with Atg13, Atg17, Atg29, and Atg31 (ULK1, ATG13, FIP200, and ATG101 in humans) has a pivotal role in the earliest steps of this process. This review summarizes recent structural and ultrastructural analysis of the earliest step in autophagosome biogenesis and discusses a model in which the Atg1 complex clusters high-curvature vesicles containing the integral membrane protein Atg9, thereby initiating the phagophore.
C1 [Stanley, Robin E.; Ragusa, Michael J.] Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Ragusa, Michael J.; Hurley, James H.] Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biosci, Berkeley, CA 94720 USA.
RP Hurley, JH (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, Calif Inst Quantitat Biosci, 229 Stanley Hall, Berkeley, CA 94720 USA.
EM jimhurley@berkeley.edu
FU Damon Runyon Cancer Research Fellowship; Ruth Kirschtein NRSA fellowship
[GM099319]
FX Research in the Hurley laboratory was supported by the Intramural
Program of the NIH, NIDDK (J.H.H.), a Damon Runyon Cancer Research
Fellowship (R.E.S.), and Ruth Kirschtein NRSA fellowship GM099319
(M.J.R.).
NR 57
TC 21
Z9 22
U1 0
U2 25
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD JAN
PY 2014
VL 24
IS 1
SI SI
BP 73
EP 81
DI 10.1016/j.tcb.2013.07.008
PG 9
WC Cell Biology
SC Cell Biology
GA 296AN
UT WOS:000330157600010
PM 23999079
ER
PT J
AU Pletnev, S
Subach, FV
Verkhusha, VV
Dauter, Z
AF Pletnev, Sergei
Subach, Fedor V.
Verkhusha, Vladislav V.
Dauter, Zbigniew
TI The rotational order-disorder structure of the reversibly
photoswitchable red fluorescent protein rsTagRFP
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID LATTICE-TRANSLOCATION DEFECTS; CO-CRYSTAL; ABSORBENCY; ANTIBODY
AB The rotational order-disorder (OD) structure of the reversibly photoswitchable fluorescent protein rsTagRFP is discussed in detail. The structure is composed of tetramers of 222 symmetry incorporated into the lattice in two different orientations rotated 90 degrees with respect to each other around the crystal c axis and with tetramer axes coinciding with the crystallographic twofold axes. The random distribution of alternatively oriented tetramers in the crystal creates the rotational OD structure with statistically averaged I422 symmetry. Despite order-disorder pathology, the structure of rsTagRFP has electron-density maps of good quality for both non-overlapping and overlapping parts of the model. The crystal contacts, crystal internal architecture and a possible mechanism of rotational OD crystal formation are discussed.
C1 [Pletnev, Sergei] Argonne Natl Lab, Basic Res Program, Leidos Biomed Res Inc, Argonne, IL 60439 USA.
[Pletnev, Sergei; Dauter, Zbigniew] Argonne Natl Lab, Macromol Crystallog Lab, NCI, Argonne, IL 60439 USA.
[Subach, Fedor V.; Verkhusha, Vladislav V.] Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
RP Pletnev, S (reprint author), Argonne Natl Lab, Basic Res Program, Leidos Biomed Res Inc, 9700 S Cass Ave, Argonne, IL 60439 USA.
EM pletnevs@mail.nih.gov; dauter@anl.gov
RI Subach, Fedor/K-7080-2014
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; National Cancer Institute, National
Institutes of Health (NIH) [HHSN261200800001E]; Intramural Research
Program of the NIH, the National Cancer Institute, the Center for Cancer
Research; NIH [GM073913, CA164468]
FX Diffraction data were collected on the SER-CAT 22BM beamline at the
Advanced Photon Source, Argonne National Laboratory. Use of the Advanced
Photon Source was supported by the US Department of Energy, Office of
Science, Office of Basic Energy Sciences under Contract No.
W-31-109-Eng-38. This work was supported in part with Federal funds from
the National Cancer Institute, National Institutes of Health (NIH)
contract No. HHSN261200800001E, the Intramural Research Program of the
NIH, the National Cancer Institute, the Center for Cancer Research and
by NIH grants GM073913 and CA164468 to VVV. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 31
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1399-0047
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD JAN
PY 2014
VL 70
BP 31
EP 39
DI 10.1107/S1399004713024644
PN 1
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 293AD
UT WOS:000329942900005
PM 24419376
ER
PT J
AU Litten, RZ
Falk, D
Ryan, M
Fertig, J
AF Litten, Raye Z.
Falk, Daniel
Ryan, Megan
Fertig, Joanne
TI Research Opportunities for Medications to Treat Alcohol Dependence:
Addressing Stakeholders' Needs
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Medication Development; Alcohol Pharmacotherapy; Research
Opportunities; Stakeholders' Needs
ID UNITED-STATES; ADDICTION; NALTREXONE; PRESCRIPTION; DISORDERS; DRINKING;
TRIALS; TRENDS; DRUG
AB During the past decade, significant advances have been made in the development of medications to treat alcohol dependence. Four medications have been approved by the U.S. Food and Drug Administration for treating alcohol dependencenaltrexone, injectable naltrexone, acamprosate, and disulfiramand several others show promise. The fact remains, however, that because of the heterogeneity of alcohol dependence, these medications will not work for all people, in all circumstances. Moreover, clinicians are not routinely prescribing these medications for alcohol treatment. This commentary poses a number of issues that must be addressed in order to advance the alcohol research field and to make medications a mainstream treatment for problematic drinking. These issues are framed from the perspective of the various stakeholders involved, including clinicians, patients, regulatory agencies, the pharmaceutical industry, and third-party payers. Addressing these issues will not only help to improve treatment but, as further described, will also open up many new research opportunities for alcohol investigators in the coming decade.
C1 [Litten, Raye Z.; Falk, Daniel; Ryan, Megan; Fertig, Joanne] NIAAA, NCIG, Div Treatment & Recovery Res, Bethesda, MD 20892 USA.
RP Litten, RZ (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane, Bethesda, MD 20892 USA.
EM rlitten@mail.nih.gov
NR 28
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JAN
PY 2014
VL 38
IS 1
BP 27
EP 32
DI 10.1111/acer.12193
PG 6
WC Substance Abuse
SC Substance Abuse
GA 292EV
UT WOS:000329885900003
PM 23889161
ER
PT J
AU Marshall, VJ
Ramchandani, VA
Kalu, N
Kwagyan, J
Scott, DM
Ferguson, CL
Taylor, RE
AF Marshall, Vanessa J.
Ramchandani, Vijay A.
Kalu, Nnenna
Kwagyan, John
Scott, Denise M.
Ferguson, Clifford L.
Taylor, Robert E.
TI Evaluation of the Influence of Alcohol Dehydrogenase Polymorphisms on
Alcohol Elimination Rates in African Americans
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Dehydrogenase Polymorphisms; Breath Alcohol Clamping; Alcohol
Elimination Rate; African Descent Population; Sib Pair Analysis
ID FAMILY-HISTORY; ADH2-ASTERISK-3 ALLELE; YOUNG-ADULTS; NATIVE-AMERICANS;
ACUTE RESPONSE; BODY-MASS; ASSOCIATION; PHARMACOKINETICS; METABOLISM;
DEPENDENCE
AB IntroductionThe relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers.
MaterialsThe sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06g% ethanol and 0mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates.
ResultsParticipants with ADH1B1/1 genotypes showed higher number of drinks (p=0.023) and drinks per drinking day (p=0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p=0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p=0.002), regardless of body weight (p=0.004) and lean body mass (p<0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p<0.001). These observations were mediated by drinks per drinking day, gender, and FHA.
ConclusionsADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.
C1 [Marshall, Vanessa J.; Kalu, Nnenna; Kwagyan, John; Scott, Denise M.; Ferguson, Clifford L.; Taylor, Robert E.] Howard Univ, Alcohol Res Ctr, Washington, DC 20059 USA.
[Ramchandani, Vijay A.] NIAAA, NIH, Bethesda, MD USA.
RP Marshall, VJ (reprint author), Howard Univ, Coll Med, Alcohol Res Ctr, 520 W St,NW Suite 3408, Washington, DC 20059 USA.
EM vjmarshall@howard.edu
FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [AA-11898,
AA-012553]; Howard University General Clinical Research Center (GCRC)
[M01-RR10284]
FX Dr. Tiebing Liang, Dr. Lucy Carr, and Tammy Graves from Indiana Alcohol
Research Center, Indiana University School of Medicine, Indianapolis,
IN, for assistance with DNA isolation and genotyping. This study was
supported by the National Institute of Alcohol Abuse and Alcoholism
(NIAAA), grant numbers AA-11898, AA-012553, Howard University General
Clinical Research Center (GCRC) Grant M01-RR10284.
NR 51
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JAN
PY 2014
VL 38
IS 1
BP 51
EP 59
DI 10.1111/acer.12212
PG 9
WC Substance Abuse
SC Substance Abuse
GA 292EV
UT WOS:000329885900008
PM 23915245
ER
PT J
AU Moon, KH
Tajuddin, N
Brown, J
Neafsey, EJ
Kim, HY
Collins, MA
AF Moon, Kwan-Hoon
Tajuddin, Nuzhath
Brown, James, III
Neafsey, Edward J.
Kim, Hee-Yong
Collins, Michael A.
TI Phospholipase A2, Oxidative Stress, and Neurodegeneration in Binge
Ethanol-Treated Organotypic Slice Cultures of Developing Rat Brain
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol; Arachidonic Acid; Organotypic; Neuroinflammation;
Endocannabinoid; Monoacylglycerol Lipase
ID OXYGEN SPECIES CONTRIBUTE; ARACHIDONIC-ACID RELEASE; IN-VIVO; INDUCED
NEUROINFLAMMATION; ALCOHOL-INTOXICATION; INDUCED APOPTOSIS; FATTY-ACIDS;
A(2); ACTIVATION; DAMAGE
AB BackgroundBrain neurodamage from chronic binge ethanol (EtOH) exposure is linked to neuroinflammation and associated oxidative stress. Using rat organotypic hippocampal-entorhinal cortical (HEC) slice cultures of developing brain age, we reported that binge EtOH promotes release of a neuroinflammatory instigator, arachidonic acid (AA), concomitant with neurodegeneration, and that mepacrine, a global inhibitor of phospholipase A2 (PLA2) enzymes mobilizing AA from phospholipids, is neuroprotective. Here, we sought with binge EtOH-treated HEC cultures to establish that PLA2 activity is responsible in part for significant oxidative stress and to ascertain the PLA2 families responsible for AA release and neurodegeneration.
MethodsHEC slices, prepared from 1-week-old rats and cultured 2 to 2.5weeks, were exposed to 100mM EtOH over 6 successive days, with 4 daytime withdrawals (no EtOH). Brain 3-nitrotyrosinated (3-NT)- and 4-hydroxy-2-nonenal (4-HNE)-adducted proteins, oxidative stress footprints, were immunoassayed on days 3 through 6, and mepacrine's effect was determined on day 6. The effects of specific PLA2 inhibitors on neurodegeneration (propidium iodide staining) and AA release (ELISA levels in media) in the cultures were then determined. Also, the effect of JZL184, an inhibitor of monoacylglycerol lipase (MAGL) which is reported to mobilize AA from endocannabinoids during neuroinflammatory insults, was examined.
Results3-NT- and 4-HNE-adducted proteins were significantly increased by the binge EtOH exposure, consistent with oxidative stress, and mepacrine prevented the increases. The PLA2 inhibitor results implicated secretory PLA2 (group II sPLA2) and to some extent Ca2+-independent cytosolic PLA2 (group VI iPLA2) in binge EtOH-induced neurotoxicity and in AA release, but surprisingly, Ca2+-dependent cytosolic PLA2 (group IV cPLA2) did not appear important. Furthermore, unlike PLA2 inhibition, MAGL inhibition failed to prevent the neurodegeneration.
ConclusionsIn these developing HEC slice cultures, pro-oxidative signaling via sPLA2 and iPLA2, but not necessarily cPLA2 or MAGL, is involved in EtOH neurotoxicity. This study provides further insights into neuroinflammatory phospholipase signaling and oxidative stress underlying binge EtOH-induced neurodegeneration in developing (adolescent age) brain in vitro.
C1 [Moon, Kwan-Hoon; Tajuddin, Nuzhath; Brown, James, III; Neafsey, Edward J.; Collins, Michael A.] Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA.
[Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD USA.
RP Collins, MA (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol, Maywood, IL 60153 USA.
EM mcollin@lumc.edu
FU National Institutes of Health National Institute of Alcohol Abuse and
Alcoholism [U01 AA018279, T32 AA13527, R21 AA011543]; Loyola University
Potts Foundation
FX This research was supported by the National Institutes of Health
National Institute of Alcohol Abuse and Alcoholism (grants U01 AA018279,
T32 AA13527, R21 AA011543) and the Loyola University Potts Foundation.
NR 55
TC 8
Z9 8
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JAN
PY 2014
VL 38
IS 1
BP 161
EP 169
DI 10.1111/acer.12221
PG 9
WC Substance Abuse
SC Substance Abuse
GA 292EV
UT WOS:000329885900020
PM 23909864
ER
PT J
AU Moore, NM
Nagahara, LA
AF Moore, Nicole M.
Nagahara, Larry A.
TI Physical Biology in Cancer. 1. Cellular physics of cancer metastasis
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE physics of cancer; cell mechanics; microfluidics
AB One of the major challenges in cancer research today is developing new therapeutic strategies to control metastatic disease, the spread of cancer cells from a primary tumor to seed in a distant site. Advances in diagnosis and treatment options have increased the survival rate for most patients with local tumors; however, less progress has been made in treatment of disseminated disease. According to the SEER Cancer Statistics Review, 19752010, in the case of breast and prostate cancers, only one in four patients diagnosed with distant metastatic disease will survive more than five years. Current research efforts largely focus on identifying biological targets, such as specific genes and signaling pathways that drive two key steps of metastasis, invasion from the primary tumor and growth in the secondary site. On the other hand, there are phenotypic traits and dynamics in the metastatic process that are not encoded by single genes or signaling pathways but, rather, a larger system of events and biophysical characteristics. Connecting genomic and pathway investigations with quantitative physical phenotypic characteristics of cells, the physical microenvironment, and the physical spatiotemporal interactions of the metastatic process provides a stronger complementary understanding of the disease.
C1 [Moore, Nicole M.; Nagahara, Larry A.] NCI, Ctr Strateg Sci Initiat, Off Phys Sci Oncol, Bethesda, MD 20892 USA.
RP Moore, NM (reprint author), NCI, Ctr Strateg Sci Initiat, Off Phys Sci Oncol, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM moorenm@mail.nih.gov
NR 10
TC 2
Z9 2
U1 1
U2 21
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JAN
PY 2014
VL 306
IS 2
BP C78
EP C79
DI 10.1152/ajpcell.00292.2013
PG 2
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 291WK
UT WOS:000329862400002
PM 24153431
ER
PT J
AU Smith, JP
Solomon, TE
AF Smith, Jill P.
Solomon, Travis E.
TI Cholecystokinin and pancreatic cancer: the chicken or the egg?
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE receptor; G protein-coupled; gastrin; cholecystokinin; pancreas; cancer
ID GASTRIN GENE-EXPRESSION; ACINAR-CELLS; FUNCTIONAL EXPRESSION; EXOCRINE
SECRETION; CCK-B; ANTAGONIST RADIOLIGAND; STIMULATES GROWTH;
MOLECULAR-CLONING; RECEPTOR FAMILY; TRANSGENIC MICE
AB The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."
C1 [Smith, Jill P.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Solomon, Travis E.] Univ Missouri, Dept Basic Med Sci, Kansas City, MO 64110 USA.
RP Smith, JP (reprint author), NIDDK, NIH, 6707 Democracy Blvd,Rm 655, Bethesda, MD 20892 USA.
EM jsmith2@psu.edu
NR 106
TC 18
Z9 18
U1 1
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
EI 1522-1547
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD JAN
PY 2014
VL 306
IS 2
BP G91
EP G101
DI 10.1152/ajpgi.00301.2013
PG 11
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 293OR
UT WOS:000329982700001
PM 24177032
ER
PT J
AU Balch, WE
Sznajder, JI
Budinger, S
Finley, D
Laposky, AD
Cuervo, AM
Benjamin, IJ
Barreiro, E
Morimoto, RI
Postow, L
Weissman, AM
Gail, D
Banks-Schlegel, S
Croxton, T
Gan, WN
AF Balch, William E.
Sznajder, Jacob I.
Budinger, Scott
Finley, Daniel
Laposky, Aaron D.
Cuervo, Ana Maria
Benjamin, Ivor J.
Barreiro, Esther
Morimoto, Richard I.
Postow, Lisa
Weissman, Allan M.
Gail, Dorothy
Banks-Schlegel, Susan
Croxton, Thomas
Gan, Weiniu
TI Malfolded Protein Structure and Proteostasis in Lung Diseases
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE protein misfolding; post-translational processing; proteosome;
ubiquitination; pulmonary health
ID OBSTRUCTIVE PULMONARY-DISEASE; ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE
STRESS; ALPHA(1)-ANTITRYPSIN DEFICIENCY; THERAPEUTIC PARADIGM;
CYSTIC-FIBROSIS; PROTEASOME; AUTOPHAGY; UBIQUITIN; INJURY
AB Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on "Malformed Protein Structure and Proteostasis in Lung Diseases" was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment.
C1 [Balch, William E.] Scripps Res Inst, Dept Cell Biol & Chem Physiol, La Jolla, CA 92037 USA.
[Sznajder, Jacob I.; Budinger, Scott] Northwestern Univ, Div Pulm & Crit Care Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Morimoto, Richard I.] Northwestern Univ, Dept Mol Biosci, Chicago, IL 60611 USA.
[Finley, Daniel] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Laposky, Aaron D.; Postow, Lisa; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas; Gan, Weiniu] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
[Cuervo, Ana Maria] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA.
[Cuervo, Ana Maria] Albert Einstein Coll Med, Inst Aging Studies, Bronx, NY 10467 USA.
[Benjamin, Ivor J.] Med Coll Wisconsin, Div Cardiovasc Med, Milwaukee, WI 53226 USA.
[Barreiro, Esther] Hosp del Mar, Dept Resp Med, Lung Canc Res Grp, Inst Med Res Hosp del Mar IMIM,CIBERES, Barcelona, Spain.
[Weissman, Allan M.] NCI, Lab Prot Dynam, Frederick, MD 21701 USA.
[Weissman, Allan M.] NCI, Signaling Ctr Canc Res, Frederick, MD 21701 USA.
RP Gan, WN (reprint author), NHLBI, NIH, 6701 Rockledge Dr,Suite 10042, Bethesda, MD 20892 USA.
EM ganw2@nhlbi.nih.gov
RI Barreiro, E/D-6919-2014
OI Barreiro, E/0000-0003-2708-3443
FU National Heart, Lung, and Blood Institute
FX Supported by the National Heart, Lung, and Blood Institute.
NR 65
TC 18
Z9 18
U1 2
U2 13
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JAN 1
PY 2014
VL 189
IS 1
BP 96
EP 103
DI 10.1164/rccm.201306-1164WS
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 290UW
UT WOS:000329784800018
PM 24033344
ER
PT S
AU Adesunloye, BA
Karzai, FH
Dahut, WL
AF Adesunloye, Bamidele A.
Karzai, Fatima H.
Dahut, William L.
BE Marone, G
Granata, F
TI Angiogenesis Inhibitors in the Treatment of Prostate Cancer
SO ANGIOGENESIS, LYMPHANGIOGENESIS AND CLINICAL IMPLICATIONS
SE Chemical Immunology and Allergy
LA English
DT Article; Book Chapter
ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL;
5,6-DIMETHYLXANTHENONE-4-ACETIC ACID DMXAA; MITOXANTRONE PLUS
PREDNISONE; MONOCLONAL-ANTIBODY J591; ADVANCED SOLID TUMORS; MEMBRANE
ANTIGEN; DOUBLE-BLIND; IN-VITRO; HEPARANASE INHIBITOR
AB Prostate cancer is the most common cancer in men in the United States and is the second most common cause of death. While treatment options in early stage disease are curative in intent, treatment of metastatic prostate cancer remains challenging. Although, several new and promising treatment options exploiting novel targets have permeated the therapeutic landscape in recent years, another viable target for therapy is tumor angiogenesis. Many antiangiogenic agents are under development and some are currently under investigation in clinical trials. Copyright (C) 2014 S. Karger AG, Basel
C1 [Adesunloye, Bamidele A.; Karzai, Fatima H.; Dahut, William L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RP Dahut, WL (reprint author), NCI, Bldg 10,Room 12N226 10 Ctr Dr, Bethesda, MD 20892 USA.
EM dahutw@mail.nih.gov
NR 114
TC 0
Z9 0
U1 0
U2 1
PU KARGER
PI BASEL
PA POSTFACH, CH-4009 BASEL, SWITZERLAND
SN 1660-2242
BN 978-3-318-02480-7; 978-3-318-02481-4
J9 CHEM IMMUNOL ALLERGY
JI Chem. Immunol. Allergy
PY 2014
VL 99
BP 197
EP 215
DI 10.1159/000353255
PG 19
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA BJM05
UT WOS:000329030400013
PM 24217611
ER
PT J
AU Milling, TJ
Brown, J
AF Milling, Truman J. TJ, Jr.
Brown, Jeremy
TI Annals Q&A With Dr. Jeremy Brown
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Editorial Material
C1 [Brown, Jeremy] NIH, OECR, Bethesda, MD USA.
[Brown, Jeremy] George Washington Univ GW, Dept Emergency Med, Washington, DC USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD JAN
PY 2014
VL 63
IS 1
BP 13A
EP 15A
DI 10.1016/j.annemergmed.2013.11.004
PG 3
WC Emergency Medicine
SC Emergency Medicine
GA 292GN
UT WOS:000329890300001
PM 24498646
ER
PT J
AU Zeng, WQ
Chen, XZ
Ma, Y
Huang, ZX
Qin, Y
Wu, FP
Wu, LL
Liang, XH
Qin, YF
Zhou, J
Lu, DC
Kuang, XC
Li, QQ
Luo, ZJ
AF Zeng, Wenqing
Chen, Xiaozhou
Ma, Yan
Huang, Zhenxing
Qin, Yuan
Wu, Fengping
Wu, Lili
Liang, Xinghuan
Qin, Yingfen
Zhou, Jia
Lu, Decheng
Kuang, Xiaocong
Li, Qingdi Quentin
Luo, Zuojie
TI A Novel Approach for Enriching Cancer Stem Cells from the Human SW-13
Adrenocortical Carcinoma Cell Line
SO ANTICANCER RESEARCH
LA English
DT Article
DE Adrenocortical carcinoma; cancer stem cell; chemotherapy; CXCR4; ABCG2;
cyclophosphamide
ID CHEMOKINE RECEPTOR CXCR4; LUNG-CANCER; CHEMOTHERAPY; METASTASIS; GROWTH;
EXPRESSION; RESISTANCE; CISPLATIN; FEATURES; TUMORS
AB The present study was undertaken to develop a new method for enriching cancer stem cells (CSCs) from the human adrenal cortical carcinoma (ACC) cell line SW-13. Given that the existence of CSCs in ACC causes resistance to conventional chemotherapies, treatment with cyclophosphamide was used for in vivo selection of CSCs in a BALB/c nude mouse tumor xenograft model established using the ACC cell line SW-13. The characteristics of CSCs in three generations of tumor xenografts were assessed for single-cell colony formation, flat colony formation, and cell sphere formation in serum-free suspension culture. The formation rates of single-cell colonies, flat colonies, and cell spheres were significantly higher for tumor xenograft cells treated with cyclophosphamide than for untreated engrafted tumor cells. Flow cytometry to examine expression of the CSC markers C-X-C chemokine receptor type-4 (CXCR4; CD184) and ATP-binding cassette sub-family G member-2 (ABCG2; CDw338) revealed markedly higher levels of CXCR4 and ABCG2 in cyclophosphamide-treated xenograft tumor cells compared to untreated tumor cells. Together, these results indicate that cyclophosphamide treatment of tumor xeno graft cells caused enrichment of CSCs with a strong capability for self-renewal and proliferation. In this method, the administration of cyclophosphamide selectively kills cancer cells without toxicity to CSCs and thereby provides a practical approach for achieving the enrichment of CSCs in ACC.
C1 [Zeng, Wenqing; Chen, Xiaozhou; Huang, Zhenxing; Qin, Yuan; Wu, Fengping; Wu, Lili; Liang, Xinghuan; Qin, Yingfen; Zhou, Jia; Lu, Decheng; Luo, Zuojie] Guangxi Med Univ, Affiliated Hosp 1, Dept Endocrinol, Nanning 530021, Peoples R China.
[Ma, Yan] Guangxi Med Univ, Affiliated Hosp 1, Dept Ultrason Diag, Nanning 530021, Peoples R China.
[Kuang, Xiaocong] Guangxi Med Univ, Dept Pathophysiol, Nanning 530021, Peoples R China.
[Li, Qingdi Quentin] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Li, QQ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM liquenti@mail.nih.gov; zluo888@163.com
FU National Natural Science Foundation of China [81060220]; Natural Science
Foundation of Guangxi [2011GXNSFA018172]
FX This work was supported by grants from the National Natural Science
Foundation of China (no. 81060220) and the Natural Science Foundation of
Guangxi (no. 2011GXNSFA018172).
NR 26
TC 3
Z9 3
U1 0
U2 5
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD JAN
PY 2014
VL 34
IS 1A
BP 117
EP 123
PG 7
WC Oncology
SC Oncology
GA 290NJ
UT WOS:000329765300012
PM 24403451
ER
PT J
AU Jakopovic, M
Thomas, A
Lopez-Chavez, A
AF Jakopovic, Marko
Thomas, Anish
Lopez-Chavez, Ariel
TI From Platinum Compounds to Targeted Therapies in Advanced Thoracic
Malignancies
SO ANTICANCER RESEARCH
LA English
DT Review
DE Platinum-based chemotherapy; advanced thoracic malignancies; targeted
therapy; review
ID CELL LUNG-CANCER; THYMIC EPITHELIAL TUMORS; EML4-ALK FUSION GENE;
PHASE-II; 1ST-LINE TREATMENT; INTERGROUP TRIAL; OPEN-LABEL; COMBINATION
CHEMOTHERAPY; ACTIVATING MUTATIONS; RECURRENT THYMOMA
AB Improved understanding of the molecular mechanisms involved in development, growth and spread of cancer have led to develpment of targeted therapies for many cancers. Based on their superior tolerability and efficacy, targeted therapies with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) or crizotinib are preferred first-line treatments over platinum-based chemotherapies in patients whose tumours harbour EGFR-activating mutations and anaplastic lymphoma kinase (ALK) translocations, respectively. Active areas of research in EGFR-mutant and ALK-translocated NSCLC include identification of mechanisms of resistance and overcoming them. Therapeutic targeting of several other targets including ROS, RET and discoidin domain receptor 2 (DDR2) tyrosine kinases are in early phases of clinical evaluation. Despite the advances in tumour genomic sequencing, a substantial fraction of patients with non-small cell lung cancer (NSCLC) do not have any targetable genetic alteration. Ongoing research is focused on identifying mechanisms of carcinogenesis in these patients. Targeted therapies in small cell lung cancer (SCLC) and thymic malignancies have not yielded meaningful clinical benefits, and platinum-based therapies remain the cornerstone of treating patients with advanced disease.
C1 [Jakopovic, Marko] Univ Zagreb, Sch Med, Dept Resp Dis, Univ Hosp Ctr Zagreb, Zagreb 41001, Croatia.
[Thomas, Anish] NCI, Thorac & GI Oncol Branch, Bethesda, MD 20892 USA.
[Lopez-Chavez, Ariel] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Lopez-Chavez, A (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA.
EM lopezcha@ohsu.edu
OI Thomas, Anish/0000-0003-3293-3115
NR 55
TC 3
Z9 3
U1 0
U2 2
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD JAN
PY 2014
VL 34
IS 1B
BP 477
EP 482
PG 6
WC Oncology
SC Oncology
GA 290NK
UT WOS:000329765400009
PM 24403504
ER
PT J
AU Doherty, B
Lawlor, D
Gillet, JP
Gottesman, M
O'Leary, JJ
Stordal, B
AF Doherty, Ben
Lawlor, Denise
Gillet, Jean-Pierre
Gottesman, Michael
O'Leary, John J.
Stordal, Britta
TI Collateral Sensitivity to Cisplatin in KB-8-5-11 Drug-resistant Cancer
Cells
SO ANTICANCER RESEARCH
LA English
DT Article
DE Cisplatin; paclitaxel; drug resistance; collateral sensitivity; cervical
cancer; KB-8-5-11 cells
ID GLUTATHIONE-S-TRANSFERASE; HUMAN OVARIAN-CARCINOMA; TRANSPORTER ATP7A;
EXPRESSION; PLATINUM; LINES; CYTOTOXICITY; GENE
AB Background: KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer. Materials and Methods: A Taqman low-density array was used to characterize the expression of 380 genes previously associated with chemoresistance. Identified pathways were further analyzed using cytotoxicity assays, metabolomics and western blots. Results: KB-8-5-11 cells were sensitive to CuSO4 and the glutathione inhibitor buthionine sulphoximine. Expression of ATPase, Cu2+ transporting alpha (ATP7A) and ATP7B were decreased at the protein and gene levels respectively in KB-8-5-11. KB-8-5-11 had decreased gene expression of glutathione S-transferase pi 1 (GSTP1), GSTA4 and GSTK1. Cisplatin treatment significantly lowered total cellular glutathione in parental KB-3-1 cells. Glutathione also tended to be lower in KB-8-5-11 cells compared to KB-3-1 cells. Conclusion: KB-8-5-11 cells have alterations in their copper transporters and glutathione metabolism, contributing to their cisplatin-sensitive phenotype.
C1 [Doherty, Ben; Lawlor, Denise; O'Leary, John J.; Stordal, Britta] St James Hosp, Dept Histopathol, Dublin 8, Ireland.
[Doherty, Ben; Lawlor, Denise; O'Leary, John J.; Stordal, Britta] Trinity Coll Dublin, Dublin, Ireland.
[Gillet, Jean-Pierre; Gottesman, Michael] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Stordal, B (reprint author), St James Hosp, Dept Histopathol, Trinity Coll Dublin, Sir Patrick Dun Res Lab 1 18, Cent Pathol Bldg, Dublin 8, Ireland.
EM stordalb@tcd.ie
FU Irish Cancer Society Postdoctoral Fellowship; Marie Curie Reintegration
Grant from the European Union FP7 programme; European Association of
Cancer Research Travel Fellowship
FX This research was funded by the following grants: Irish Cancer Society
Postdoctoral Fellowship (BS), Marie Curie Reintegration Grant from the
European Union FP7 programme (BS) and a European Association of Cancer
Research Travel Fellowship (BS).
NR 18
TC 1
Z9 1
U1 0
U2 1
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD JAN
PY 2014
VL 34
IS 1B
BP 503
EP 507
PG 5
WC Oncology
SC Oncology
GA 290NK
UT WOS:000329765400013
PM 24403508
ER
PT J
AU Lee, J
Armstrong, DT
Ssengooba, W
Park, JA
Yu, Y
Mumbowa, F
Namaganda, C
Mboowa, G
Nakayita, G
Armakovitch, S
Chien, G
Cho, SN
Via, LE
Barry, CE
Ellner, JJ
Alland, D
Dorman, SE
Joloba, ML
AF Lee, Jongseok
Armstrong, Derek T.
Ssengooba, Willy
Park, Jeong-Ae
Yu, Yeuni
Mumbowa, Francis
Namaganda, Carolyn
Mboowa, Gerald
Nakayita, Germine
Armakovitch, Sandra
Chien, Gina
Cho, Sang-Nae
Via, Laura E.
Barry, Clifton E., III
Ellner, Jerrold J.
Alland, David
Dorman, Susan E.
Joloba, Moses L.
TI Sensititre MYCOTB MIC Plate for Testing Mycobacterium tuberculosis
Susceptibility to First- and Second-Line Drugs
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID RESISTANT TUBERCULOSIS; AGAR PROPORTION; MUTATIONS; DIAGNOSIS
AB For Mycobacterium tuberculosis, phenotypic methods for drug susceptibility testing of second-line drugs are poorly standardized and technically challenging. The Sensititre MYCOTB MIC plate (MYCOTB) is a microtiter plate containing lyophilized antibiotics and configured for determination of MICs to first- and second-line antituberculosis drugs. To evaluate the performance of MYCOTB for M. tuberculosis drug susceptibility testing using the Middlebrook 7H10 agar proportion method (APM) as the comparator, we conducted a two-site study using archived M. tuberculosis isolates from Uganda and the Republic of Korea. Thawed isolates were subcultured, and dilutions were inoculated into MYCOTB wells and onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, and 21; APM results were read at 21 days. A total of 222 isolates provided results on both platforms. By APM, 106/222 (47.7%) of isolates were resistant to at least isoniazid and rifampin. Agreement between MYCOTB and APM with respect to susceptibility or resistance was >= 92% for 7 of 12 drugs when a strict definition was used and >= 96% for 10 of 12 drugs when agreement was defined by allowing a +/- one-well range of dilutions around the APM critical concentration. For ethambutol, agreement was 80% to 81%. For moxifloxacin, agreement was 83% to 85%; incorporating existing DNA sequencing information for discrepant analysis raised agreement to 91% to 96%. For MYCOTB, the median time to plate interpretation was 10 days and interreader agreement was >= 95% for all drugs. MYCOTB provided reliable results for M. tuberculosis susceptibility testing of first-and second-line drugs except ethambutol, and results were available sooner than those determined by APM.
C1 [Lee, Jongseok; Park, Jeong-Ae; Yu, Yeuni; Cho, Sang-Nae] Int TB Res Ctr, Masan, South Korea.
[Armstrong, Derek T.; Dorman, Susan E.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Ssengooba, Willy; Mumbowa, Francis; Namaganda, Carolyn; Mboowa, Gerald; Nakayita, Germine; Joloba, Moses L.] Makerere Univ, Mycobacteriol Lab, Kampala, Uganda.
[Armakovitch, Sandra; Chien, Gina; Ellner, Jerrold J.] Boston Univ, Med Ctr, Boston, MA USA.
[Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Alland, David] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA.
RP Dorman, SE (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
EM DSUSAN1@JHMI.EDU
RI Barry, III, Clifton/H-3839-2012;
OI Mboowa, Gerald/0000-0001-8445-9414; Via, Laura/0000-0001-6074-9521;
Ssengooba, Willy/0000-0002-1643-110X; Joloba, Moses/0000-0002-0334-9983
FU National Institute of Allergy and Infectious Diseases (NIAID)
[HHSN2722000900050C]; U.S. Intramural Research Program of NIAID,
National Institutes of Health, Department of Health and Human Services
FX This work was funded by contract HHSN2722000900050C from the National
Institute of Allergy and Infectious Diseases (NIAID) and in part by the
U.S. Intramural Research Program of NIAID, National Institutes of
Health, Department of Health and Human Services.
NR 24
TC 16
Z9 18
U1 2
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2014
VL 58
IS 1
BP 11
EP 18
DI 10.1128/AAC.01209-13
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 287ZL
UT WOS:000329581100002
PM 24100497
ER
PT J
AU Barton, C
Kouokam, JC
Lasnik, AB
Foreman, O
Cambon, A
Brock, G
Montefiori, DC
Vojdani, F
McCormick, AA
O'Keefe, BR
Palmer, KE
AF Barton, Christopher
Kouokam, J. Calvin
Lasnik, Amanda B.
Foreman, Oded
Cambon, Alexander
Brock, Guy
Montefiori, David C.
Vojdani, Fakhrieh
McCormick, Alison A.
O'Keefe, Barry R.
Palmer, Kenneth E.
TI Activity of and Effect of Subcutaneous Treatment with the Broad-Spectrum
Antiviral Lectin Griffithsin in Two Laboratory Rodent Models
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID HEPATITIS-C VIRUS; ENTRY INHIBITOR GRIFFITHSIN; N-LINKED GLYCANS;
CYANOVIRIN-N; CARBOHYDRATE-BINDING; PROTEIN GRIFFITHSIN; TYPE-1 STRAINS;
IN-VITRO; GP120; RESISTANCE
AB Griffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.
C1 [Barton, Christopher; Kouokam, J. Calvin; Lasnik, Amanda B.; Palmer, Kenneth E.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Barton, Christopher; Kouokam, J. Calvin; Lasnik, Amanda B.; Palmer, Kenneth E.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
[Kouokam, J. Calvin; Palmer, Kenneth E.] Owensboro Canc Res Program, Owensboro, KY USA.
[Foreman, Oded] Jackson Lab, Bar Harbor, ME 04609 USA.
[Cambon, Alexander; Brock, Guy] Univ Louisville, Dept Bioinformat & Biostat, Louisville, KY 40292 USA.
[Montefiori, David C.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA.
[Vojdani, Fakhrieh; Palmer, Kenneth E.] Intrucept Biomed LLC, Owensboro, KY USA.
[McCormick, Alison A.] Touro Coll Pharm, Vallejo, CA USA.
[O'Keefe, Barry R.] NCI, Frederick, MD 21701 USA.
RP Palmer, KE (reprint author), Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
EM kenneth.palmer@louisville.edu
OI Palmer, Kenneth/0000-0002-2811-1111
FU NIH [AI076169, T32-ES011564, HHSN27201100016C]; DOD [USAMRMC
W81XWH-10-2-CLIN 1]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This work was supported by NIH grant AI076169 to K.E.P. and NIH grant
T32-ES011564, DOD grant USAMRMC W81XWH-10-2-CLIN 1, and NIH contract
HHSN27201100016C. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 42
TC 26
Z9 26
U1 4
U2 16
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2014
VL 58
IS 1
BP 120
EP 127
DI 10.1128/AAC.01407-13
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 287ZL
UT WOS:000329581100015
PM 24145548
ER
PT J
AU Debing, Y
Emerson, SU
Wang, YJ
Pan, QW
Balzarini, J
Dallmeier, K
Neyts, J
AF Debing, Yannick
Emerson, Suzanne U.
Wang, Yijin
Pan, Qiuwei
Balzarini, Jan
Dallmeier, Kai
Neyts, Johan
TI Ribavirin Inhibits In Vitro Hepatitis E Virus Replication through
Depletion of Cellular GTP Pools and Is Moderately Synergistic with Alpha
Interferon
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID FAMILY HEPEVIRIDAE; ANTIVIRAL ACTIVITY; MYCOPHENOLIC-ACID; INFECTION;
DEHYDROGENASE; THERAPY; BIOSYNTHESIS; FLAVIVIRUSES; MECHANISM; GENOTYPE
AB Hepatitis E virus (HEV) is a common cause of acute hepatitis that results in high mortality in pregnant women and may establish chronic infections in immunocompromised patients. We demonstrate for the first time that alpha interferon (IFN-alpha) and ribavirin inhibit in vitro HEV replication in both a subgenomic replicon and an infectious culture system based on a genotype 3 strain. IFN-alpha showed a moderate but significant synergism with ribavirin. These findings corroborate the reported clinical effectiveness of both drugs. In addition, the antiviral activity of ribavirin against wild-type genotype 1, 2, and 3 strains was confirmed by immunofluorescence staining. Furthermore, the in vitro activity of ribavirin depends on depletion of intracellular GTP pools, which is evident from the facts that (i) other GTP-depleting agents (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide [EICAR] and mycophenolic acid) inhibit viral replication, (ii) exogenously added guanosine reverses the antiviral effects, and (iii) a strong correlation (R-2 = 0.9998) exists between the antiviral activity and GTP depletion of ribavirin and other GTP-depleting agents.
C1 [Debing, Yannick; Pan, Qiuwei; Balzarini, Jan; Dallmeier, Kai; Neyts, Johan] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Louvain, Belgium.
[Emerson, Suzanne U.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Yijin; Pan, Qiuwei] Erasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.
RP Neyts, J (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Louvain, Belgium.
EM johan.neyts@rega.kuleuven.be
OI Debing, Yannick/0000-0001-6566-9408
FU European Association; KU Leuven Geconcerteerde Onderzoeksacties
[GOA/10/014]; EU FP7 project SILVER [260644]; National Institutes of
Health, National Institute of Allergy and Infectious Diseases
FX Y.D. is a fellow of the Research Foundation-Flanders (FWO). Q.P. is
supported by a Sheila Sherlock Fellowship from the European Association
for the Study of the Liver (EASL). This work was supported by KU Leuven
Geconcerteerde Onderzoeksacties (GOA/10/014) and by EU FP7 project
SILVER (260644) and in part by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases (S.U.E.).
NR 43
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U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2014
VL 58
IS 1
BP 267
EP 273
DI 10.1128/AAC.01795-13
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 287ZL
UT WOS:000329581100033
PM 24145541
ER
PT J
AU Gupta, S
Cohen, KA
Winglee, K
Maiga, M
Diarra, B
Bishai, WR
AF Gupta, Shashank
Cohen, Keira A.
Winglee, Kathryn
Maiga, Mamoudou
Diarra, Bassirou
Bishai, William R.
TI Efflux Inhibition with Verapamil Potentiates Bedaquiline in
Mycobacterium tuberculosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID MULTIDRUG-RESISTANT TUBERCULOSIS; DRUG-RESISTANCE; DIARYLQUINOLINE
TMC207; REVERSAL
AB Drug efflux is an important resistance mechanism in Mycobacterium tuberculosis. We found that verapamil, an efflux inhibitor, profoundly decreases the MIC of bedaquiline and clofazimine to M. tuberculosis by 8- to 16-fold. This exquisite susceptibility was noted among drug-susceptible and drug-resistant clinical isolates. Thus, efflux inhibition is an important sensitizer of bedaquiline and clofazimine, and efflux may emerge as a resistance mechanism to these drugs.
C1 [Gupta, Shashank; Winglee, Kathryn; Maiga, Mamoudou; Bishai, William R.] JHU, Dept Med, Ctr TB Res, Baltimore, MD USA.
[Gupta, Shashank; Bishai, William R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Cohen, Keira A.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Cohen, Keira A.; Bishai, William R.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa.
[Maiga, Mamoudou; Diarra, Bassirou] Univ Bamako Res Collaborat HIV TB, Project SEREFO NIAID, Bamako, Mali.
RP Bishai, WR (reprint author), JHU, Dept Med, Ctr TB Res, Baltimore, MD USA.
EM wbishai@jhmi.edu
RI Gupta, Shashank/E-7382-2016
OI Gupta, Shashank/0000-0003-0445-5195
FU NIAID [AI 079590, AI 037856, AI 036973]; NHLBI [T32HL007633]; Howard
Hughes Medical Institute
FX This work was supported by grants AI 079590, AI 037856, and AI 036973
from NIAID, T32HL007633 from the NHLBI, and the Howard Hughes Medical
Institute.
NR 18
TC 44
Z9 45
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JAN
PY 2014
VL 58
IS 1
BP 574
EP 576
DI 10.1128/AAC.01462-13
PG 3
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 287ZL
UT WOS:000329581100073
PM 24126586
ER
PT J
AU Komatsu, TE
Pikis, A
Naeger, LK
Harrington, PR
AF Komatsu, Takashi E.
Pikis, Andreas
Naeger, Lisa K.
Harrington, Patrick R.
TI Resistance of human cytomegalovirus to ganciclovir/valganciclovir: A
comprehensive review of putative resistance pathways
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Cytomegalovirus; Ganciclovir; Valganciclovir; Resistance; Cidofovir;
Foscarnet
ID DNA-POLYMERASE MUTATIONS; ORGAN TRANSPLANT RECIPIENTS; STEM-CELL
TRANSPLANTATION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; OPEN READING FRAME;
ANTICYTOMEGALOVIRUS COMPOUND AIC246; CONFERRING FOSCARNET RESISTANCE;
PLAQUE REDUCTION ASSAY; GANCICLOVIR-RESISTANT; DRUG-RESISTANCE
AB Human cytomegalovirus (HCMV) is a pathogen that can be life-threatening in immunocompromised individuals. Valganciclovir and its parent drug ganciclovir are currently the principle drugs used for the treatment or prevention of HCMV disease. The development of HCMV resistance to ganciclovir/valganciclovir has been documented in treated patients and is associated with the emergence of amino acid substitutions in the viral proteins pUL97, pUL54 or both. Generally, single amino acid substitutions associated with clinical resistance that alone do not confer decreased ganciclovir susceptibility in cell culture have been disregarded as causative or clinically significant. This review focuses on the analysis and mechanisms of antiviral drug resistance to HCMV. We also conducted a review of publicly available clinical and nonclinical data to construct a comprehensive list of pUL97 and pUL54 amino acid substitutions that are associated with a poor clinical response to the first line therapies ganciclovir and valganciclovir, or associated with reduced HCMV ganciclovir susceptibility in cell culture. Over 40 putative ganciclovir/valganciclovir resistance-associated substitutions were identified in this analysis. These include the commonly reported substitutions M460I/V and C592G in pUL97. There were additional substitutions that are not widely considered as ganciclovir/valganciclovir resistance-associated substitutions, including V466M in pUL97 and E315D in pUL54. Some of these ganciclovir/valganciclovir resistance-associated substitutions may confer cross-resistance to other HCMV therapies, such as cidofovir and foscarnet. Based on this review, we propose that there are more potential HCMV ganciclovir/valganciclovir resistance pathways than generally appreciated. The resulting comprehensive list of putative ganciclovir/valganciclovir resistance-associated substitutions provides a foundation for future investigations to characterize the role of specific substitutions or combinations of substitutions, which will enhance our understanding of HCMV mechanisms of ganciclovir/valganciclovir resistance and also provide insight regarding the potential for cross-resistance to other HCMV therapies. Published by Elsevier B.V.
C1 [Komatsu, Takashi E.; Pikis, Andreas; Naeger, Lisa K.; Harrington, Patrick R.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Pikis, Andreas] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Komatsu, TE (reprint author), US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22 Room 6323, Silver Spring, MD 20993 USA.
EM Takashi.Komatsu@fda.hhs.gov
FU Intramural Research Program of the National Institute of Dental and
Craniofacial Research, National Institutes of Health, Department of
Health and Human Services, Bethesda, Maryland
FX We thank Debra Birnkrant, Mike Bray, Edward Cox, Jeffrey Murray, Jules
O'Rear, and Kuate Seraphin for helpful manuscript suggestions and
discussion. A.P. is supported in part by the Intramural Research Program
of the National Institute of Dental and Craniofacial Research, National
Institutes of Health, Department of Health and Human Services, Bethesda,
Maryland.
NR 191
TC 21
Z9 23
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
EI 1872-9096
J9 ANTIVIR RES
JI Antiviral Res.
PD JAN
PY 2014
VL 101
BP 12
EP 25
DI 10.1016/j.antiviral.2013.10.011
PG 14
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 290QF
UT WOS:000329772700002
PM 24184129
ER
PT J
AU Beidas, RS
Lindhiem, O
Brodman, DM
Swan, A
Carper, M
Cummings, C
Kendall, PC
Albano, AM
Rynn, M
Piacentini, J
McCracken, J
Compton, SN
March, J
Walkup, J
Ginsburg, G
Keeton, CP
Birmaher, B
Sakolsky, D
Sherrill, J
AF Beidas, Rinad S.
Lindhiem, Oliver
Brodman, Douglas M.
Swan, Anna
Carper, Matthew
Cummings, Colleen
Kendall, Philip C.
Albano, Anne Marie
Rynn, Moira
Piacentini, John
McCracken, James
Compton, Scott N.
March, John
Walkup, John
Ginsburg, Golda
Keeton, Courtney P.
Birmaher, Boris
Sakolsky, Dara
Sherrill, Joel
TI A Probabilistic and Individualized Approach for Predicting Treatment
Gains: An Extension and Application to Anxiety Disordered Youth
SO BEHAVIOR THERAPY
LA English
DT Article
DE child/adolescent anxiety; evidence-based treatment; individualized
treatment benefit; patient-centered decision-making; treatment response
and outcome
ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CLINICAL-TRIAL; CHILDHOOD
ANXIETY; PSYCHOTHERAPY-RESEARCH; TREATMENT RESPONSE; CHILDREN;
ADOLESCENTS; VARIABILITY; COMORBIDITY; REMISSION
AB The objective of this study was to extend the probability of treatment benefit method by adding treatment condition as a stratifying variable, and illustrate this extension of the methodology using the Child and Adolescent Anxiety Multimodal Study data. The probability of treatment benefit method produces a simple and practical way to predict individualized treatment benefit based on pretreatment patient characteristics. Two pretreatment patient characteristics were selected in the production of the probability of treatment benefit charts: baseline anxiety severity, measured by the Pediatric Anxiety Rating Scale, and treatment condition (cognitive-behavioral therapy, sertraline, their combination, and placebo). We produced two charts as exemplars which provide individualized and probabilistic information for treatment response and outcome to treatments for child anxiety. We discuss the implications of the use of the probability of treatment benefit method, particularly with regard to patient-centered outcomes and individualized decision-making in psychology and psychiatry.
C1 [Beidas, Rinad S.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Lindhiem, Oliver; Birmaher, Boris; Sakolsky, Dara] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Brodman, Douglas M.; Swan, Anna; Carper, Matthew; Cummings, Colleen; Kendall, Philip C.] Temple Univ, Philadelphia, PA 19122 USA.
[Albano, Anne Marie; Rynn, Moira] Columbia Univ, New York, NY 10027 USA.
[Piacentini, John; McCracken, James] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Compton, Scott N.; March, John] Duke Child & Family Study Ctr, Durham, NC USA.
[Walkup, John] Cornell Univ, Ithaca, NY 14853 USA.
[Ginsburg, Golda; Keeton, Courtney P.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Sherrill, Joel] NIMH, Bethesda, MD USA.
RP Beidas, RS (reprint author), Univ Penn, 3535 Market St,3015, Philadelphia, PA 19104 USA.
EM rbeidas@upenn.edu
FU NIMH NIH HHS [U01 MH064088, U01 MH064107, U01 MH64088, U01 MH64107, K01
MH93508, K01 MH093508, K23 MH099179, K23 MH99179, K24 MH096760, R25
MH080916, U01 MH063747, U01 MH064003, U01 MH064089, U01 MH064092, U01
MH64003, U01 MH64092, U01MH63747, U01MH64003]
NR 48
TC 6
Z9 6
U1 1
U2 8
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
EI 1878-1888
J9 BEHAV THER
JI Behav. Therapy
PD JAN
PY 2014
VL 45
IS 1
BP 126
EP 136
PG 11
WC Psychology, Clinical
SC Psychology
GA 294XG
UT WOS:000330080600013
PM 24411120
ER
PT J
AU Qi, RX
Luo, Y
Ma, BY
Nussinov, R
Wei, GH
AF Qi, Ruxi
Luo, Yin
Ma, Buyong
Nussinov, Ruth
Wei, Guanghong
TI Conformational Distribution and alpha-Helix to beta-Sheet Transition of
Human Amylin Fragment Dimer
SO BIOMACROMOLECULES
LA English
DT Article
ID ISLET AMYLOID POLYPEPTIDE; MOLECULAR-DYNAMICS SIMULATIONS;
NMR-SPECTROSCOPY; MEMBRANE ENVIRONMENT; FIBER FORMATION; PI-STACKING;
PEPTIDE; PROTEIN; IAPP; OLIGOMERS
AB Experiments suggested that the fibrillation of the 11-25 fragment (hIAPP(11-25)) of human islet amyloid polypeptide (hIAPP or amylin) involves the formation of transient alpha-helical intermediates, followed by conversion to beta-sheet-rich structure. However, atomic details of alpha-helical intermediates and the transition mechanism are mostly unknown. We investigated the structural properties of the monomer and dimer in atomistic detail by replica exchange molecular dynamics (REMD) simulations. Transient alpha-helical monomers and dimers were both observed in the REMD trajectories. Our calculated H-alpha chemical shifts based on the monomer REMD run are in agreement with the solution-state NMR experimental observations. Multiple 300 ns MD simulations at 310 K show that alpha-helix-to-beta-sheet transition follows two mechanisms: the first involved direct transition of the random coil part of the helical conformation into antiparallel beta-sheet, and in the second, the alpha-helical conformation unfolded and converted into antiparallel beta-sheet. In both mechanisms, the alpha-helix-to-beta-sheet transition occurred via random coil, and the transition was accompanied by an increase of interpeptide contacts. In addition, our REMD simulations revealed different temperature dependencies of helical and beta-structures. Comparison with experimental data suggests that the propensity for hIAPP(11-25) to form alpha-helices and amyloid structures is concentration- and temperature-dependent.
C1 [Qi, Ruxi; Luo, Yin; Wei, Guanghong] Fudan Univ, State Key Lab Surface Phys, Key Lab Computat Phys Sci MOE, Shanghai 200433, Peoples R China.
[Qi, Ruxi; Luo, Yin; Wei, Guanghong] Fudan Univ, Dept Phys, Shanghai 200433, Peoples R China.
[Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Ma, BY (reprint author), NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU NSF of China [91227102, 11074047, 11274075]; Research Fund for the
Doctoral Program of Higher Education of China; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; NIH,
National Cancer Institute, Center for Cancer Research
FX G.W. acknowledges the financial support from the NSF of China (Grant
Nos. 91227102, 11074047, and 11274075) and the Research Fund for the
Doctoral Program of Higher Education of China. Simulations were
performed at the Shanghai Supercomputing Center and the National High
Performance Computing Center of Fudan University. This project has been
funded in whole or in part with Federal funds from the National Cancer
Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 87
TC 23
Z9 23
U1 4
U2 50
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1525-7797
EI 1526-4602
J9 BIOMACROMOLECULES
JI Biomacromolecules
PD JAN
PY 2014
VL 15
IS 1
BP 122
EP 131
DI 10.1021/bm401406e
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science
SC Biochemistry & Molecular Biology; Chemistry; Polymer Science
GA 292CO
UT WOS:000329879800014
PM 24313776
ER
PT J
AU Speer, AM
Wassermann, EM
Benson, BE
Herscovitch, P
Post, RM
AF Speer, Andrew M.
Wassermann, Eric M.
Benson, Brenda E.
Herscovitch, Peter
Post, Robert M.
TI Antidepressant Efficacy of High and Low Frequency rTMS at 110% of Motor
Threshold versus Sham Stimulation over Left Prefrontal Cortex
SO BRAIN STIMULATION
LA English
DT Article
DE Left prefrontal cortex; Major depression; Motor threshold; rTMS; Sham
ID TRANSCRANIAL MAGNETIC STIMULATION; MAJOR DEPRESSIVE DISORDER; CEREBRAL
GLUCOSE-METABOLISM; ELECTROCONVULSIVE-THERAPY; RANDOMIZED-TRIAL;
RESISTANT DEPRESSION; DURATION; NUMBER; TMS
AB Background: While the efficacy of repetitive transcranial magnetic stimulation (rTMS) at 10 Hz over the left prefrontal cortex has been repeatedly demonstrated, it is not clear that the optimal parameters for the treatment of depression have been adequately elucidated.
Objectives: We sought to assess the antidepressant effectiveness of high and low frequency at a higher intensity rTMS compared to sham in patients with moderately treatment resistant depression.
Method: The authors conducted a three-week, double-blind, randomized, sham-controlled study of 24 acutely depressed patients given either active 20 Hz (n = 8) or 1 Hz (n = 8) rTMS (at 110% of motor threshold [MT]) or sham treatments (n = 8) over the left prefrontal cortex. Hamilton Depression ratings were analyzed by ANOVA.
Results: Patients on both frequencies showed greater improvement than on sham, which was associated with minor increases in depression. During open continuation to allow 7 weeks of active treatment in all individuals, additional improvement was observed.
Conclusions: The results seen here using 110% of MT for 3 weeks were more robust than those of previous studies of 1-Hz or 20-Hz rTMS for 2 weeks (at 80% and 100% of MT). The results also raise the possibility that both high and low frequency rTMS over left prefrontal cortex (and not just low frequency over the right prefrontal cortex) exert antidepressant effects, but further work is required to assess what parameters may be most effective in general and for a given individual. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Speer, Andrew M.] Lab Brain & Cognit, Bethesda, MD 20814 USA.
[Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, DHHS, Bethesda, MD 20892 USA.
[Benson, Brenda E.] NIMH, Mood & Anxiety Disorder Branch, NIH, DHHS, Bethesda, MD USA.
[Herscovitch, Peter] NIH, PET Dept, Ctr Clin, DHHS, Bethesda, MD USA.
[Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD 20814 USA.
RP Post, RM (reprint author), Bipolar Collaborat Network, 5415 W Cedar Lane,Suite 201-B, Bethesda, MD 20814 USA.
EM robert.post@speakeasy.net
NR 35
TC 6
Z9 9
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1935-861X
EI 1876-4754
J9 BRAIN STIMUL
JI Brain Stimul.
PD JAN-FEB
PY 2014
VL 7
IS 1
BP 36
EP 41
DI 10.1016/j.brs.2013.07.004
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 293BV
UT WOS:000329947300006
PM 23928104
ER
PT J
AU Rogers, T
Ratnayaka, K
Lederman, RJ
AF Rogers, Toby
Ratnayaka, Kanishka
Lederman, Robert J.
TI MRI Catheterization in Cardiopulmonary Disease
SO CHEST
LA English
DT Article
ID CARDIOVASCULAR-MAGNETIC-RESONANCE; PULMONARY ARTERIAL-HYPERTENSION;
VENTRICULAR SYSTOLIC FUNCTION; CONGENITAL HEART-DISEASE;
CARDIAC-CATHETERIZATION; TRICUSPID REGURGITATION; NONINVASIVE
ESTIMATION; EXERCISE CAPACITY; EJECTION FRACTION; PROGNOSTIC VALUE
AB Diagnosis and prognostication in patients with complex cardiopulmonary disease can be a clinical challenge. A new procedure, MRI catheterization, involves invasive right-sided heart catheterization performed inside the MRI scanner using MRI instead of traditional radiographic fluoroscopic guidance. MRI catheterization combines simultaneous invasive hemodynamic and MRI functional assessment in a single radiation-free procedure. By combining both modalities, the many individual limitations of invasive catheterization and noninvasive imaging can be overcome, and additional clinical questions can be addressed. Today, MRI catheterization is a clinical reality in specialist centers in the United States and Europe. Advances in medical device design for the MRI environment will enable not only diagnostic but also interventional MRI procedures to be performed within the next few years.
C1 [Rogers, Toby; Ratnayaka, Kanishka; Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713,MSC 1538, Bethesda, MD 20892 USA.
EM lederman@nih.gov
OI Rogers, Toby/0000-0002-6043-3137; lederman, robert/0000-0003-1202-6673
FU Intramural NIH HHS; NHLBI NIH HHS [Z01 HL005062]
NR 48
TC 7
Z9 7
U1 0
U2 2
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JAN
PY 2014
VL 145
IS 1
BP 30
EP 36
DI 10.1378/chest.13-1759
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 293JD
UT WOS:000329966300014
PM 24394821
ER
PT J
AU Cai, X
Pacheco-Rodriguez, G
Haughey, M
Samsel, L
Xu, SW
Wu, HP
McCoy, JP
Stylianou, M
Darling, TN
Moss, J
AF Cai, Xiong
Pacheco-Rodriguez, Gustavo
Haughey, Mary
Samsel, Leigh
Xu, Suowen
Wu, Hai-Ping
McCoy, J. Philip
Stylianou, Mario
Darling, Thomas N.
Moss, Joel
TI Sirolimus Decreases Circulating Lymphangioleiomyomatosis Cells in
Patients With Lymphangioleiomyomatosis
SO CHEST
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; TSC2
LOSS; GROWTH; METASTASIS; GENE; SURVIVAL; DISEASE
AB Background: Lymphangioleiomyomatosis (LAM), sporadic or in women with tuberous sclerosis complex (TSC), is characterized by cystic lung destruction, lymphatic involvement (eg, chylous pleural effusions, lymphangioleiomyomas), and renal angiomyolipomas (AMLs). The multisystem manifestations of LAM appear to result from metastatic dissemination of LAM cells bearing inactivating mutations or having loss of heterozygosity (LOH) of the tumor suppressor genes TSC1 or TSC2, which leads to hyperactivation of the mammalian target of rapamycin. Sirolimus slows the decline of lung function, reduces chylous effusions, and shrinks the size of AMLs. The purpose of this study was to determine the effect of sirolimus on circulating LAM cells.
Methods: Cells from blood were isolated by a density-gradient fractionation system and from urine and chylous effusions by centrifugation. Blood cells were incubated with anti-CD45-fluorescein isothiocyanate (FITC) and anti-CD235a-R-phycoerythrin (PE) antibodies, and urine and chylous effusion cells were incubated with anti-CD44v6-FITC and anti-CD9-R-PE antibodies. Cells were sorted and analyzed for TSC2 LOH.
Results: LAM cells with TSC2 LOH were identified in 100% of blood specimens and 75% of urine samples from patients before therapy. Over a mean duration of 2.2 +/- 0.4 years of sirolimus therapy, detection rates of LAM cells were significantly decreased to 25% in blood (P < .001) and 8% in urine (P = .003). Following therapy, a greater loss of circulating LAM cells was seen in postmenopausal patients (P = .025).
Conclusions: Patients receiving sirolimus had a progressive loss of circulating LAM cells that depended on time of treatment and menopausal status.
C1 [Cai, Xiong; Pacheco-Rodriguez, Gustavo; Haughey, Mary; Xu, Suowen; Wu, Hai-Ping; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Samsel, Leigh; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
[Stylianou, Mario] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D05,MSC 1590,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
OI Darling, Thomas/0000-0002-5161-1974
FU Intramural Research Program of the National Institutes of Health,
National Heart, Lung, and Blood Institute; [R01-AR062080]
FX This study was funded in part by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood Institute
[to Dr Moss], and R01-AR062080 [to Dr Darling].
NR 19
TC 15
Z9 15
U1 0
U2 6
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JAN
PY 2014
VL 145
IS 1
BP 108
EP +
DI 10.1378/chest.13-1071
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 293JD
UT WOS:000329966300025
PM 24051985
ER
PT J
AU Shah, AM
Cheng, SS
Skali, H
Wu, J
Mangion, JR
Kitzman, D
Matsushita, K
Konety, S
Butler, KR
Fox, ER
Cook, N
Ni, HY
Coresh, J
Mosley, TH
Heiss, G
Folsom, AR
Solomon, SD
AF Shah, Amil M.
Cheng, Susan
Skali, Hicham
Wu, Justina
Mangion, Judy R.
Kitzman, Dalane
Matsushita, Kunihiro
Konety, Suma
Butler, Kenneth R.
Fox, Ervin R.
Cook, Nakela
Ni, Hanyu
Coresh, Josef
Mosley, Thomas H.
Heiss, Gerardo
Folsom, Aaron R.
Solomon, Scott D.
TI Rationale and Design of a Multicenter Echocardiographic Study to Assess
the Relationship Between Cardiac Structure and Function and Heart
Failure Risk in a Biracial Cohort of Community-Dwelling Elderly Persons
The Atherosclerosis Risk in Communities Study
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE aging; echocardiography; epidemiology
ID LEFT-VENTRICULAR MASS; PRESERVED EJECTION FRACTION; WHITE ADULT MEN;
GENERAL-POPULATION; EUROPEAN-ASSOCIATION; DIASTOLIC FUNCTION;
AMERICAN-SOCIETY; PREVALENCE; DYSFUNCTION; WOMEN
AB Background Heart failure is an important public health concern, particularly among persons >65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community.
Methods and Results The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute-sponsored epidemiological cohort study. Between 2011 and 2013, approximate to 6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure.
Conclusions We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.
C1 [Shah, Amil M.; Cheng, Susan; Skali, Hicham; Wu, Justina; Mangion, Judy R.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Kitzman, Dalane] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Matsushita, Kunihiro; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Konety, Suma] Univ Minnesota, Sch Med, Div Cardiol, Minneapolis, MN 55455 USA.
[Butler, Kenneth R.; Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med Geriatr Gerontol, Jackson, MS USA.
[Fox, Ervin R.] Univ Mississippi, Med Ctr, Div Cardiovasc Dis, Jackson, MS USA.
[Cook, Nakela; Ni, Hanyu] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Heiss, Gerardo] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
RP Shah, AM (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boson, MA 02445 USA.
EM ashah11@partners.org
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100
009C, HHSN268201100010C, HHSN268201100011C, HHSN26 8201100012C,
NHLBI-HC-11-08, 1K08HL116792-01A1]
FX The ARIC study is performed as a collaborative study supported by
National Heart, Lung, and Blood Institute (NHLBI) contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100 009C, HHSN268201100010C,
HHSN268201100011C, and HHSN26 8201100012C). This work was also supported
by NHLBI cooperative agreement NHLBI-HC-11-08 (Brigham and Women's
Hospital) and grant 1K08HL116792-01A1 (to Dr Shah).
NR 33
TC 21
Z9 21
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JAN
PY 2014
VL 7
IS 1
BP 173
EP 181
DI 10.1161/CIRCIMAGING.113.000736
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 293BF
UT WOS:000329945700023
PM 24214885
ER
PT J
AU Stetler-Stevenson, WG
Gavil, NV
AF Stetler-Stevenson, William G.
Gavil, Noah Veis
TI Normalization of the tumor microenvironment: evidence for tissue
inhibitor of metalloproteinase-2 as a cancer therapeutic
SO CONNECTIVE TISSUE RESEARCH
LA English
DT Article
DE Angiogenesis; extracellular matrix; homeostasis; metalloproteinases;
progression
ID SINGLE NUCLEOTIDE POLYMORPHISMS; MATRIX-METALLOPROTEINASE; ANGIOGENESIS
INHIBITOR; EXTRACELLULAR-MATRIX; COMBINATION THERAPY; ENDOTHELIAL-CELLS;
GROWTH; TIMP-2; GENE; INVASION
AB Matrix metalloproteinases (MMPs) are members of the Metzincin family of proteases responsible for degrading the extracellular matrix (ECM). In early studies, MMP degradation of the sub-epithelial basement membrane was thought to be tumor cell autonomous and contribute to the invasive behavior of malignant cells. It is now recognized that MMPs have multiple roles that can either promote or inhibit tumor progression and metastasis. The endogenous inhibitors of the MMPs are the tissue inhibitors of metalloproteinases (TIMPs). Early studies on the tumor microenvironment revealed TIMP function to be principally through the inhibition of MMPs, thereby blocking tumor cell migration and invasion. However, data from a number of laboratories are now reporting that TIMPs have direct cellular functions, independent of their MMP inhibitory activity. The TIMPs can modulate normal tissue physiology and development, as well as pathology and progression in a variety of acute and chronic disease states. In this review, we briefly describe the role of MMPs and TIMPs in ECM turnover and formation of the tumor microenvironment. Based on the evidence presented, we postulate that TIMP-2 and other soluble components of the normal ECM may provide a novel therapeutic approach to cancer treatment through "normalization" of the tumor microenvironment.
C1 [Stetler-Stevenson, William G.] NIH, Senior Biomed Res Serv, Bethesda, MD 20892 USA.
[Stetler-Stevenson, William G.] NCI, Extracellular Matrix Pathol Sect, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gavil, Noah Veis] Bowdoin Coll, Brunswick, ME 04011 USA.
[Gavil, Noah Veis] NCI, Canc Res Summer Interns Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Stetler-Stevenson, WG (reprint author), Adv Technol Ctr, Radiat Oncol Branch, 8717 Grovemont Circle,Room 115, Gaithersburg, MD 20877 USA.
EM sstevenw@mail.nih.gov
RI Stetler-Stevenson, William/H-6956-2012;
OI Stetler-Stevenson, William/0000-0002-5500-5808; Gavil,
Noah/0000-0003-4686-4181
FU NCI
FX The authors thank D. Sandra Jensen-Taubman for helpful discussions and
assistance in editing the manuscript. The authors are honored and
pleased to contribute to this issue of Connective Tissue Research
dedicated to Dr Arthur Veis, former and founding Editor-in-Chief of this
journal. WGSS - Arthur Veis, PhD, was my advisor and mentor during my
PhD studies in the Medical Scientist Training Program from 1975 through
1983 at the Northwestern University Feinberg School of Medicine. I am
very grateful to Arthur for his encouragement and support both during my
time at Northwestern, as well as my tenure at NCI for the last 26 years.
Arthur continues to teach his students and post-doctoral fellows as a
Professor Emeritus through a masterly balance of guidance and creative
freedom as he has for over 50 years. During this time, he has nurtured
many scientific careers, and his students and fellows have gone on to
establish their own exceptional careers in academia and biotechnology.
What impresses me the most over the many years that I have known Arthur
is his compassion and generosity. I will always remember my time as a
graduate student in his laboratory as the best years of my career, as it
was not only productive, but also fun. NVG-Arthur Veis, PhD, is my
grandfather, and his encouragement, support, and clear love of his
vocation have inspired me to pursue a degree in biochemistry at Bowdoin
College. My sincerest thanks go to Dr. Stetler-Stevenson, who graciously
welcomed me into his lab during the summer of 2012 as a young
undergraduate and invited me to join him in this tribute. Dr.
Stetler-Stevenson has further inspired me with his wonderful mentorship,
and I am especially grateful for the stories he tells that convey his
nostalgia and admiration for the days he spent in the Veis Lab.
NR 50
TC 10
Z9 11
U1 0
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0300-8207
EI 1607-8438
J9 CONNECT TISSUE RES
JI Connect. Tissue Res.
PD JAN-FEB
PY 2014
VL 55
IS 1
BP 13
EP 19
DI 10.3109/03008207.2013.867339
PG 7
WC Cell Biology; Orthopedics
SC Cell Biology; Orthopedics
GA 291ZG
UT WOS:000329870800004
PM 24437600
ER
PT J
AU Liu, Y
Litiere, S
de Vries, EGE
Sargent, D
Shankar, L
Bogaerts, J
Seymour, L
AF Liu, Yan
Litiere, Saskia
de Vries, Elisabeth G. E.
Sargent, Daniel
Shankar, Lalitha
Bogaerts, Jan
Seymour, Lesley
CA RECIST Comm
TI The role of response evaluation criteria in solid tumour in anticancer
treatment evaluation: Results of a survey in the oncology community
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE RECIST; Tumour assessment criteria; Targeted agents; FDG-PET; Advanced
MR techniques
ID POSITRON-EMISSION-TOMOGRAPHY; IMATINIB MESYLATE; RECIST GUIDELINE;
CLINICAL-TRIALS; WORKING GROUP; CANCER; RECOMMENDATIONS; PET
AB Purpose: With the increasing use of novel targeted agents and the development of high imaging techniques, response evaluation criteria in solid tumour (RECIST) 1.1 developed primarily for cytotoxic agents and anatomic imaging, has demonstrated limitations. A survey was conducted of RECIST users to identify concerns and their suggestions for future RECIST criteria.
Methods: 140 key partners of the RECIST collaboration were asked to complete a questionnaire. The 49 questions concerned (a) satisfaction and concerns with RECIST 1.1; (b) use of modified RECIST criteria and (c) suggestions for the next RECIST Version.
Results: Sixty-five replies were received. 52.3% responders were satisfied with RECIST 1.1, while 10.8% indicated dissatisfaction. Areas of potential weakness included: (a) lack of incorporation of potential early indicators of response such as functional imaging, (b) lack of validation in rarer tumour types and (c) lack of validation for novel (targeted) agents. Suggestions were multiple, with highest numbers on two points: developing sub-criteria for certain disease types and including advanced imaging techniques for the evaluation.
Conclusions: Constructive suggestions were received for optimising the next version. Ongoing data collection will make it possible to investigate the possible utilisation of fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in tumour assessment, to verify whether RECIST is/can still be applicable in novel targeted therapy and to consider the need for criteria for specific disease types. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Liu, Yan; Litiere, Saskia; Bogaerts, Jan] EORTC, B-1200 Brussels, Belgium.
[de Vries, Elisabeth G. E.] Univ Groningen, Univ Med Ctr Groningen, Dept Med Oncol, Groningen, Netherlands.
[Seymour, Lesley] Queens Univ, Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada.
[Sargent, Daniel] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Shankar, Lalitha] NCI, Canc Imaging Program, Bethesda, MD 20892 USA.
RP Liu, Y (reprint author), EORTC, Translat Res Radiotherapy & Imaging Dept, Ave E Mounier 83-11, B-1200 Brussels, Belgium.
EM yan.liu@eortc.be
OI Sargent, Daniel/0000-0002-2684-4741
FU EORTC Charitable Trust
FX This publication was supported by the EORTC Charitable Trust. The
authors wish to thank the members of the RECIST Working Group for their
generous participation: Janet Dancey, Robert Ford, Steve Gwyther, Wendy
Hayes, Otto Hoekstra, Eric Huang, Sumithra Mandrekar, Margaret Mooney,
Larry Rubinstein, Larry Schwartz, Patrick Therasse and Helen Young.
NR 27
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U1 1
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD JAN
PY 2014
VL 50
IS 2
BP 260
EP 266
DI 10.1016/j.ejca.2013.10.011
PG 7
WC Oncology
SC Oncology
GA 293PV
UT WOS:000329986500002
PM 24239447
ER
PT J
AU Bulliard, JL
Garcia, M
Blom, J
Senore, C
Mai, V
Klabunde, C
AF Bulliard, Jean-Luc
Garcia, Montse
Blom, Johannes
Senore, Carlo
Mai, Verna
Klabunde, Carrie
TI Sorting out measures and definitions of screening participation to
improve comparability: The example of colorectal cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Review
DE Participation; Definition; Colorectal cancer; Screening; Programme
ID OCCULT BLOOD-TEST; RANDOMIZED CONTROLLED-TRIAL; FECAL IMMUNOCHEMICAL
TEST; LONGITUDINAL ADHERENCE; QUALITY-ASSURANCE; PILOT PROGRAM;
POPULATION; COLONOSCOPY; MAMMOGRAPHY; SIGMOIDOSCOPY
AB Participation is a key indicator of the potential effectiveness of any population-based intervention. Defining, measuring and reporting participation in cancer screening programmes has become more heterogeneous as the number and diversity of interventions have increased, and the purposes of this benchmarking parameter have broadened. This study, centred on colorectal cancer, addresses current issues that affect the increasingly complex task of comparing screening participation across settings. Reports from programmes with a defined target population and active invitation scheme, published between 2005 and 2012, were reviewed. Differences in defining and measuring participation were identified and quantified, and participation indicators were grouped by aims of measure and temporal dimensions. We found that consistent terminology, clear and complete reporting of participation definition and systematic documentation of coverage by invitation were lacking. Further, adherence to definitions proposed in the 2010 European Guidelines for Quality Assurance in Colorectal Cancer Screening was suboptimal. Ineligible individuals represented 1% to 15% of invitations, and variable criteria for ineligibility yielded differences in participation estimates that could obscure the interpretation of colorectal cancer screening participation internationally. Excluding ineligible individuals from the reference population enhances comparability of participation measures. Standardised measures of cumulative participation to compare screening protocols with different intervals and inclusion of time since invitation in definitions are urgently needed to improve international comparability of colorectal cancer screening participation. Recommendations to improve comparability of participation indicators in cancer screening interventions are made. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Bulliard, Jean-Luc] Univ Inst Social & Prevent Med, Canc Epidemiol Unit, Lausanne, Switzerland.
[Garcia, Montse] Catalan Inst Oncol, Canc Prevent & Control Program, IDIBELL, Lhospitalet De Llobregat, Spain.
[Blom, Johannes] Karolinska Inst, Dept Mol Med & Surg, Karolinska Univ Hosp, Stockholm, Sweden.
[Senore, Carlo] CPO Piemonte, AO Citta Salute & Sci, Turin, Italy.
[Mai, Verna] Canadian Partnership Canc, Toronto, ON, Canada.
[Klabunde, Carrie] NCI, Bethesda, MD 20892 USA.
RP Bulliard, JL (reprint author), Inst Univ Med Sociale & Prevent, Unite Epidemiol Canc, Biopole 2,Rte Corniche 10, CH-1010 Lausanne, Switzerland.
EM Jean-Luc.Bulliard@chuv.ch
RI Garcia, Montse/B-8832-2014;
OI Garcia, Montse/0000-0002-3437-3185; Senore, Carlo/0000-0003-1023-7477
FU Carlos III Health Institute [RD/12/0036/0053]
FX The International Cancer Screening Network (ICSN) is acknowledged for
their leadership. The authors are indebted to Gregory Doyle (Canada),
Lea Hagoel-Salomon (Israel), Iben Holten (Denmark), Julietta Patnick
(UK) and Sven Tornberg (Sweden) for their collaboration in the ICSN
Screening Participation Rates working group. M. G. acknowledges the
support from the Carlos III Health Institute (RD/12/0036/0053).
NR 68
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U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD JAN
PY 2014
VL 50
IS 2
BP 434
EP 446
DI 10.1016/j.ejca.2013.09.015
PG 13
WC Oncology
SC Oncology
GA 293PV
UT WOS:000329986500021
PM 24144735
ER
PT J
AU Nath, A
Steiner, J
AF Nath, Avindra
Steiner, Joseph
TI Synaptodendritic injury with HIV-Tat protein: What is the therapeutic
target?
SO EXPERIMENTAL NEUROLOGY
LA English
DT Editorial Material
ID MEMORY DEFICITS; IMMUNODEFICIENCY; RECEPTOR; ACTIVATION; EXPRESSION;
BRAIN; MOUSE
C1 [Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Nath, Avindra; Steiner, Joseph] NINDS, Translat Neurosci Ctr, NIH, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), Room 7C-103,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS003130-06]
NR 26
TC 7
Z9 8
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD JAN
PY 2014
VL 251
BP 112
EP 114
DI 10.1016/j.expneurol.2013.11.004
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 293DI
UT WOS:000329951200012
PM 24246278
ER
PT J
AU Dutta, A
Chatterjee, R
Chaudhuri, K
AF Dutta, Avirup
Chatterjee, Raghunath
Chaudhuri, Keya
TI Identification of C. elegans & C-briggsae miRNAs by modified miRsearch
SO FRONTIERS IN BIOSCIENCE-LANDMARK
LA English
DT Article
DE miRNA; C. elegans and C. briggasae miRNA; Modified Mirsearch
ID MICRORNA GENES; SMALL RNAS; BIOGENESIS; DROSOPHILA; TARGETS; ENCODES
AB In this study, a modified miRsearch program was developed in C++ for the detection of miRNAs. All the mature miRNA sequences of Caenorhabditis elegans, Caenorhabditis briggsae, Caenorhabditis remanei, Drosophila melanogaster, Homo sapiens and Rattus norvegicus available in miRbase was searched by this program for homologous sequences with a maximum of 3mismatches in the chromosomes of C. elegans excluding the miRNAs of C. elegans. The same strategy was repeated for C. briggsae excluding C. briggsae miRNAs. The probable pre-miRNA sequences with stem loop secondary structures were assessed by implementation of longest-common- subsequence (LCS) algorithm with appropriate scoring system. As miRNA genes could be on either strand, each sequence was searched in both forward and reverse strands. The putative miRNAs were viewed through Mapviewer to identify their intronic or intergenic location in C. elegans and C. briggsae genomes. Further, the quality of stem-loop formation of the remaining pre-miRNA sequences was assessed through RNAFOLD. This algorithm will be helpful in detection of potential miRNAs in future sequencing data, making this an invaluable tool for miRNA prediction.
C1 [Dutta, Avirup; Chaudhuri, Keya] Indian Inst Chem Biol, Mol & Human Genet Div, Kolkata 700032, India.
[Chatterjee, Raghunath] NCI, NIH, Bethesda, MD 20892 USA.
[Chatterjee, Raghunath] ISI, Div Biol Sci, Human Genet Unit, Kolkata 700108, India.
RP Chaudhuri, K (reprint author), CSIR Indian Inst Chem Biol, Mol & Human Genet Div, 4,Raja SC Mullick Rd, Kolkata 700032, India.
EM keya.chaudhuri@gmail.com
FU Council of Scientific and Industrial Research (CSIR), Govt. of India;
CSIR Senior Research Fellowship
FX Avirup Dutta and Raghunath Chatterjee have equally contributed to this
manuscript. The study was supported by the Council of Scientific and
Industrial Research (CSIR), Govt. of India. A.D. is the recipient of the
CSIR Senior Research Fellowship.
NR 30
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U1 0
U2 2
PU FRONTIERS IN BIOSCIENCE INC
PI IRVINE
PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA
SN 1093-9946
EI 1093-4715
J9 FRONT BIOSCI-LANDMRK
JI Front. Biosci.
PD JAN 1
PY 2014
VL 19
BP 504
EP 514
DI 10.2741/4221
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 294FQ
UT WOS:000330029100008
PM 24389198
ER
PT J
AU Wivel, NA
AF Wivel, Nelson A.
TI Historical Perspectives Pertaining to the NIH Recombinant DNA Advisory
Committee
SO HUMAN GENE THERAPY
LA English
DT Editorial Material
AB Science is host to a constantly emerging series of new paradigms, and it is this characteristic that makes science both interesting and dynamic. As a part of this continuum, it became possible to create recombinant DNA molecules. Immediately it was recognized that there was a potential for serious adverse events associated with this new technology. Following two scientific conferences at Asilomar, California, the National Institutes of Health moved quickly to create the Recombinant DNA Advisory Committee (RAC). For approximately 38 years the RAC has served as an open forum for review of various recombinant DNA experiments, and for the last 23 years it has played a pivotal role in the oversight of human gene therapy. The RAC's existence obviated the need for more restrictive governmental legislation and has supported the development of genetic interventions that are leading to actual human therapies.
C1 [Wivel, Nelson A.] NIH, NIH Off Recombinant DNA Act, Bethesda, MD 20892 USA.
[Wivel, Nelson A.] NIH, RAC, Bethesda, MD 20892 USA.
[Wivel, Nelson A.] Univ Penn, Sch Med, Inst Human Gene Therapy, Philadelphia, PA 19104 USA.
RP Wivel, NA (reprint author), NIH, NIH Off Recombinant DNA Act, Bldg 10, Bethesda, MD 20892 USA.
EM nawdoc@msn.com
NR 12
TC 2
Z9 2
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JAN 1
PY 2014
VL 25
IS 1
BP 19
EP 24
DI 10.1089/hum.2013.2524
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 291SC
UT WOS:000329848600005
PM 24444182
ER
PT J
AU Singh, UP
Singh, NP
Guan, HB
Busbee, B
Price, RL
Taub, DD
Mishra, MK
Fayad, R
Nagarkatti, M
Nagarkatti, PS
AF Singh, Udai P.
Singh, Narendra P.
Guan, Hongbing
Busbee, Brandon
Price, Robert L.
Taub, Dennis D.
Mishra, Manoj K.
Fayad, Raja
Nagarkatti, Mitzi
Nagarkatti, Prakash S.
TI The Emerging Role of Leptin Antagonist as Potential Therapeutic Option
for Inflammatory Bowel Disease
SO INTERNATIONAL REVIEWS OF IMMUNOLOGY
LA English
DT Review
DE Crohn's disease (CD); inflammation; inflammatory bowel disease (IBD);
leptin antagonist; pegylated leptin; ulcerative colitis (UC)
ID REGULATORY T-CELLS; NECROSIS-FACTOR-ALPHA; PLASMA LEPTIN; INTESTINAL
INFLAMMATION; CROHNS-DISEASE; ADIPOSE-TISSUE; SERUM LEPTIN; AUTOIMMUNE
ENCEPHALOMYELITIS; PROINFLAMMATORY CYTOKINES; ULCERATIVE-COLITIS
AB Inflammatory bowel disease (IBD) is a chronic relapsing immune-mediated inflammatory disorder that affects millions of people around the world. Leptin is a satiety hormone produced primarily by adipose tissue and acts both centrally and peripherally. Leptin has been shown to play a major role in regulating metabolism, which increases during IBD progression. Leptin mediates several physiological functions including elevated blood pressure, tumorogenesis, cardiovascular pathologies and enhanced immune response in many autoimmune diseases. Recent development of a leptin mutant antagonist that blocks leptin activity raises great hope and opens up new possibilities for therapy in many autoimmune diseases including IBD. To this end, preliminary data from an ongoing study in our laboratory on pegylated leptin antagonist mutant L39A/D40A/F41A (PEG-MLA) treatment shows an inhibition of chronic colitis in IL-10(-/-) mice. PEG-MLA effectively attenuates the overall clinical scores, reverses colitis-associated pathogenesis including a decrease in body weight, and decreases systemic leptin level. PEG-MLA induces both central and peripheral leptin deficiency by mediating the cellular immune response. In summary, after blocking leptin activity, the correlative outcome between leptin-mediated cellular immune response, systemic leptin levels, and amount of adipose tissue together may provide new strategies for therapeutic intervention in autoimmune diseases, especially for intestinal inflammation.
C1 [Singh, Udai P.; Singh, Narendra P.; Guan, Hongbing; Busbee, Brandon; Nagarkatti, Mitzi; Nagarkatti, Prakash S.] Univ S Carolina, Dept Pathol Microbiol & Immunol, Sch Med, Columbia, SC 29208 USA.
[Price, Robert L.] Univ S Carolina, Dept Cell & Dev Biol, Columbia, SC 29208 USA.
[Taub, Dennis D.] NIA, Lab Mol Biol & Immunol, IRP, NIH, Baltimore, MD 21224 USA.
[Mishra, Manoj K.] Alabama State Univ, Dept Math & Sci, Montgomery, AL 36101 USA.
[Fayad, Raja] Univ S Carolina, Arnold Sch Publ Hlth, Dept Exercise Sci, Columbia, SC 29208 USA.
RP Singh, UP (reprint author), Univ S Carolina, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA.
EM Udai.singh@uscmed.sc.edu
OI Nagarkatti, Mitzi/0000-0002-5977-5615
FU NIH [R56 DK087836, P01 AT003961]; Research and Development Funds from
the University of South Carolina School of Medicine; Intramural Program
of the National Institute on Aging, NIH
FX This work was supported, in part by NIH grants R56 DK087836 and P01
AT003961, Research and Development Funds from the University of South
Carolina School of Medicine, and the Intramural Program of the National
Institute on Aging, NIH.
NR 92
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U1 1
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0883-0185
EI 1563-5244
J9 INT REV IMMUNOL
JI Int. Rev. Immunol.
PD JAN
PY 2014
VL 33
IS 1
BP 23
EP 33
DI 10.3109/08830185.2013.809071
PG 11
WC Immunology
SC Immunology
GA 291MV
UT WOS:000329833700004
PM 23841494
ER
PT J
AU Mordini, FE
Haddad, T
Hsu, LY
Kellrnan, P
Lowrey, TB
Aletras, AH
Bandettini, P
Arai, AE
AF Mordini, Federico E.
Haddad, Tariq
Hsu, Li-Yueh
Kellrnan, Peter
Lowrey, Tracy B.
Aletras, Anthony H.
Bandettini, Patricia
Arai, Andrew E.
TI Diagnostic Accuracy of Stress Perfusion CMR in Comparison With
Quantitative Coronary Angiography
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac magnetic resonance; myocardial ischemia; myocardial perfusion;
quantitative perfusion; stress testing
ID CARDIAC MAGNETIC-RESONANCE; POSITRON-EMISSION-TOMOGRAPHY; ABSOLUTE
MYOCARDIAL-PERFUSION; FRACTIONAL FLOW RESERVE; ARTERY-DISEASE;
COMPUTED-TOMOGRAPHY; NONINVASIVE DETECTION; STENOSIS SEVERITY;
TRANSIT-TIME; N-13 AMMONIA
AB OBJECTIVES This study's primary objective was to determine the sensitivity, specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic resonance (CMR) versus a reference standard of quantitative coronary angiography. We hypothesized that fully quantitative analysis of stress perfusion CMR would have high diagnostic accuracy for identifying significant coronary artery stenosis and exceed the accuracy of semiquantitative measures of perfusion and qualitative interpretation.
BACKGROUND Relatively few studies apply fully quantitative CMR perfusion measures to patients with coronary disease and comparisons to semiquantitative and qualitative methods are limited.
METHODS Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients with clinical indications for assessment of myocardial ischemia. Stress perfusion images alone were analyzed with a fully quantitative perfusion (QP) method and 3 semiquantitative methods including contrast enhancement ratio, upslope index, and upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late gadolinium enhancement) were analyzed qualitatively with 2 methods including the Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by quantitative coronary angiography was considered abnormal.
RESULTS The optimum diagnostic threshold for QP determined by receiver-operating characteristic curve occurred when endocardial flow decreased to <50% of mean epicardial flow, which yielded a sensitivity of 87% and specificity of 93%. The area under the curve for QP was 92%, which was superior to semiquantitative methods: contrast enhancement ratio: 78%; upslope index: 82%; and upslope integral: 75% (p = 0.011, p = 0.019, p = 0.004 vs. QP, respectively). Area under the curve for QP was also superior to qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p < 0.001 and p < 0.001 vs. QP, respectively).
CONCLUSIONS Fully quantitative stress perfusion CMR has high diagnostic accuracy for detecting obstructive coronary artery disease. QP outperforms semiquantitative measures of perfusion and qualitative methods that incorporate a combination of cine, perfusion, and late gadolinium enhancement imaging. These findings suggest a potential clinical role for quantitative stress perfusion CMR. (C) 2014 by the American College of Cardiology Foundation
C1 [Mordini, Federico E.; Haddad, Tariq; Hsu, Li-Yueh; Kellrnan, Peter; Lowrey, Tracy B.; Aletras, Anthony H.; Bandettini, Patricia; Arai, Andrew E.] Natl Heart Lung & Blood Inst, Cardiovasc & Pulm Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Mordini, Federico E.] Vet Affairs Med Ctr, Dept Cardiol, Washington, DC 20422 USA.
[Aletras, Anthony H.] Univ Cent Greece, Dept Biomed Informat, Lamia, Greece.
RP Arai, AE (reprint author), Natl Heart Lung & Blood Inst, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room BID 416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
FU Division of Intramural Research; National Heart, Lung, and Blood
Institute; National Institutes of Health; Siemens Medical Imaging
(United States Government Cooperative Research and Development Award)
FX From the *Cardiovascular and Pulmonary Branch, National Heart, Lung, and
Blood Institute, National Institutes of Health, Department of Health and
Human Services, Bethesda, Maryland; dagger Department of Cardiology,
Veterans Affairs Medical Center, Washington, DC; and the double dagger
Department of Biomedical Informatics, University of Central Greece,
Lamia, Greece. This study was funded by the Division of Intramural
Research, National Heart, Lung, and Blood Institute, National Institutes
of Health. Dr. Arai receives research support from Siemens Medical
Imaging (United States Government Cooperative Research and Development
Award). All other authors have reported that they have no relationships
relevant to the contents of this paper to disclose.
NR 44
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U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JAN
PY 2014
VL 7
IS 1
BP 14
EP 22
DI 10.1016/j.jcmg.2013.08.014
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 293EF
UT WOS:000329953500003
PM 24433707
ER
PT J
AU Hruby, A
O'Donnell, CJ
Jacques, PF
Meigs, JB
Hoffmann, U
McKeown, NM
AF Hruby, Adela
O'Donnell, Christopher J.
Jacques, Paul F.
Meigs, James B.
Hoffmann, Udo
McKeown, Nicola M.
TI Magnesium Intake Is Inversely Associated With Coronary Artery
Calcification
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE abdominal aortic calcification; computed tomography; coronary artery
calcification; diet; Framingham Heart Study; magnesium
ID DIETARY MAGNESIUM; CARDIOVASCULAR-DISEASE; ATHEROSCLEROTIC PLAQUE;
RISK-FACTORS; HEART; CALCIUM; SERUM; CONSUMPTION; MORTALITY; INSULIN
AB OBJECTIVES The aim of this study was to examine whether magnesium intake is associated with coronary artery calcification (CAC) and abdominal aortic calcification (AAC).
BACKGROUND Animal and cell studies suggest that magnesium may prevent calcification within atherosclerotic plaques underlying cardiovascular disease. Little is known about the association of magnesium intake and atherosclerotic calcification in humans.
METHODS We examined cross-sectional associations of self-reported total (dietary and supplemental) magnesium intake estimated by food frequency questionnaire with CAC and AAC in participants of the Framingham Heart Study who were free of cardiovascular disease and underwent Multi-Detector Computed Tomography (MDCT) of the heart and abdomen (n = 2,695; age: 53 11 years), using multivariate-adjusted Tobit regression. CAC and AAC were quantified using modified Agatston scores (AS). Models were adjusted for age, sex, body mass index, smoking status, systolic blood pressure, fasting insulin, total-to-high-density lipoprotein cholesterol ratio, use of hormone replacement therapy (women only), menopausal status (women only), treatment for hyperlipidemia, hypertension, cardiovascular disease prevention, or diabetes, as well as self-reported intake of calcium, vitamins D and K, saturated fat, fiber, alcohol, and energy. Secondary analyses included logistic regressions of CAC and AAC outcomes as cut-points (AS >0 and AS >= 90th percentile for age and sex), as well as sex-stratified analyses.
RESULTS In fully adjusted models, a 50-mg/day increment in self-reported total magnesium intake was associated with 22% lower CAC (p < 0.001) and 12% lower AAC (p = 0.07). Consistent with these observations, the odds of having any CAC were 58% lower (p trend: <0.001) and any AAC were 34% lower (p trend: 0.01), in those with the highest compared to those with the lowest magnesium intake. Stronger inverse associations were observed in women than in men.
CONCLUSIONS In community-dwelling participants free of cardiovascular disease, self-reported magnesium intake was inversely associated with arterial calcification, which may play a contributing role in magnesium's protective associations in stroke and fatal coronary heart disease. (C) 2014 by the American College of Cardiology Foundation
C1 [Hruby, Adela; Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Framingham, MA USA.
[O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA.
[O'Donnell, Christopher J.; Meigs, James B.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP McKeown, NM (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Epidemiol Program, 711 Washington St,9th Floor, Boston, MA 02111 USA.
EM nicola.mckeown@tufts.edu
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; American Heart Association Predoctoral Fellowship;
United States Department of Agriculture (USDA) [58-1950-0-014]; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K24
DK080140]
FX From the *Nutritional Epidemiology Program, Jean Mayer USDA Human
Nutrition Research Center on Aging at Tufts University, Boston,
Massachusetts; dagger National Heart, Lung, and Blood Institute (NHLBI)
Division of Intramural Research, and NHLBI's Framingham Heart Study,
Framingham, Massachusetts; double dagger Cardiovascular Division,
Department of Medicine, Massachusetts General Hospital, Boston,
Massachusetts; Harvard Medical School, Boston, Massachusetts; (General
Medicine Division, Department of Medicine, Massachusetts General
Hospital, Boston, Massachusetts; and the Massachusetts General Hospital
Cardiac MR PET CT Program and the Department of Radiology, Massachusetts
General Hospital, Boston, Massachusetts. At the time of writing, Dr.
Hruby was supported by an American Heart Association Predoctoral
Fellowship. This work was also supported by the National Heart, Lung,
and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195)
and the United States Department of Agriculture (USDA agreement no.
58-1950-0-014). Dr. Jacques has been a member of the Bay State Milling
Nutrition Science Advisory Council and of the Dannon Yogurt Advisory
Board. Dr. Meigs is supported by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) (K24 DK080140). All authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 49
TC 28
Z9 30
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JAN
PY 2014
VL 7
IS 1
BP 59
EP 69
DI 10.1016/j.jcmg.2013.10.006
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 293EF
UT WOS:000329953500009
PM 24290571
ER
PT J
AU Yuan, A
Xu, JF
Zheng, G
AF Yuan, Ao
Xu, Jinfeng
Zheng, Gang
TI On empirical likelihood statistical functions
SO JOURNAL OF ECONOMETRICS
LA English
DT Article
DE Empirical likelihood; Quantile estimation; Uniform SLLN; Uniform CLT
ID KERNEL DENSITY-ESTIMATION; AUXILIARY INFORMATION; CONFIDENCE-INTERVALS;
MOMENT RESTRICTIONS; BANACH-SPACE; LINEAR-MODELS; INFERENCE; QUANTILES
AB We consider the empirical likelihood method for estimation of distribution and quantile functions where side information is incorporated through moment conditions. We systematically study the asymptotic properties of the estimators, such as the uniform strong laws of large numbers and weak convergence over classes of functions. Two Monte Carlo examples are also given to illustrate the practical utility of the method. (C) 2013 Elsevier B.V. All rights reserved.
C1 Georgetown Univ, Washington, DC 20057 USA.
NYU, New York, NY 10016 USA.
NHLBI, Bethesda, MD 20892 USA.
RP Yuan, A (reprint author), 2216 6th St NW,Suite 206, Washington, DC 20059 USA.
EM yuanao@hotmail.com
FU National Center for Research Resources at NIH [2G12RR003048]
FX We are grateful to the editor, associate editor and two referees for
their helpful comments, which have greatly improved the manuscript. This
work is supported in part by the National Center for Research Resources
at NIH grant 2G12RR003048.
NR 42
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0304-4076
EI 1872-6895
J9 J ECONOMETRICS
JI J. Econom.
PD JAN
PY 2014
VL 178
BP 613
EP 623
DI 10.1016/j.jeconom.2013.08.037
PN 3
PG 11
WC Economics; Mathematics, Interdisciplinary Applications; Social Sciences,
Mathematical Methods
SC Business & Economics; Mathematics; Mathematical Methods In Social
Sciences
GA 293HC
UT WOS:000329961000017
ER
PT J
AU Zebrack, B
Kent, EE
Keegan, THM
Kato, I
Smith, AW
AF Zebrack, Brad
Kent, Erin E.
Keegan, Theresa H. M.
Kato, Ikuko
Smith, Ashley Wilder
CA AYA HOPE Study Collaborative Grp
TI "Cancer Sucks," and Other Ponderings by Adolescent and Young Adult
Cancer Survivors
SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY
LA English
DT Article
DE adolescent; young adult; medical care; qualitative research;
psychosocial
ID PSYCHOSOCIAL IMPACT; SERVICE NEEDS; HEALTH; OLDER; INFORMATION;
DIAGNOSIS; FAMILIES
AB As part of the National Cancer Institute's AYA HOPE study, 296 adolescent and young adults (AYAs) completed an open-ended survey item asking them to describe their medical care or experience with cancer. Patient, provider, and system-level characteristics all appear to influence AYAs' perceptions of their medical care. Participants attributed levels of satisfaction with care to the availability and communication of information, the management of side-effects, and the expediency and flexibility of treatments. Struggles with health insurance and finances were evident. Findings contribute to a better understanding of AYAs' cancer treatment experiences and will inform improvements to oncology care for this population.
C1 [Zebrack, Brad] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA.
[Kent, Erin E.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Keegan, Theresa H. M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Keegan, Theresa H. M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kato, Ikuko] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA.
[Kato, Ikuko] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA.
[Smith, Ashley Wilder] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA.
RP Zebrack, B (reprint author), Univ Michigan, Sch Social Work, 1080 S Univ, Ann Arbor, MI 48109 USA.
EM zebrack@umich.edu
FU NCI NIH HHS [N01 PC035139, N01 PC035142, N01 PC035136, N01-PC-35136,
N01-PC-35139, N01-PC-35142, N01-PC-35143, N01-PC-35145, N01-PC-54402,
N01-PC-54404, N01PC35136, N01PC35139, N01PC35142, N01PC35143,
N01PC35145, N01PC54402, N01PC54404]
NR 30
TC 11
Z9 11
U1 0
U2 9
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0734-7332
EI 1540-7586
J9 J PSYCHOSOC ONCOL
JI J. Psychosoc. Oncol.
PD JAN 1
PY 2014
VL 32
IS 1
BP 1
EP +
DI 10.1080/07347332.2013.855959
PG 13
WC Psychology, Social
SC Psychology
GA 289NI
UT WOS:000329688800007
PM 24428248
ER
PT J
AU Rebok, GW
Ball, K
Guey, LT
Jones, RN
Kim, HY
King, JW
Marsiske, M
Morris, JN
Tennstedt, SL
Unverzagt, FW
Willis, SL
AF Rebok, George W.
Ball, Karlene
Guey, Lin T.
Jones, Richard N.
Kim, Hae-Young
King, Jonathan W.
Marsiske, Michael
Morris, John N.
Tennstedt, Sharon L.
Unverzagt, Frederick W.
Willis, Sherry L.
CA ACTIVE Study Grp
TI Ten-Year Effects of the Advanced Cognitive Training for Independent and
Vital Elderly Cognitive Training Trial on Cognition and Everyday
Functioning in Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE cognitive training; elderly; cognitive abilities; everyday function;
training maintenance
ID INSTRUMENTAL ACTIVITIES; HOME-CARE; FOLLOW-UP; MDS-HC; MEMORY;
INTERVENTIONS; COMMUNITY; OUTCOMES; PROGRAM; DECLINE
AB ObjectivesTo determine the effects of cognitive training on cognitive abilities and everyday function over 10years.
DesignTen-year follow-up of a randomized, controlled single-blind trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)) with three intervention groups and a no-contact control group.
SettingSix U.S. cities.
ParticipantsA volunteer sample of 2,832 persons (mean baseline age 73.6; 26% African American) living independently.
InterventionTen training sessions for memory, reasoning, or speed of processing; four sessions of booster training 11 and 35months after initial training.
MeasurementsObjectively measured cognitive abilities and self-reported and performance-based measures of everyday function.
ResultsParticipants in each intervention group reported less difficulty with instrumental activities of daily living (IADLs) (memory: effect size=0.48, 99% confidence interval (CI)=0.12-0.84; reasoning: effect size=0.38, 99% CI=0.02-0.74; speed of processing: effect size=0.36, 99% CI=0.01-0.72). At a mean age of 82, approximately 60% of trained participants, versus 50% of controls (P<.05), were at or above their baseline level of self-reported IADL function at 10years. The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10years (reasoning: effect size=0.23, 99% CI=0.09-0.38; speed of processing: effect size=0.66, 99% CI=0.43-0.88). Memory training effects were no longer maintained for memory performance. Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance (effect size=0.21, 99% CI=0.01-0.41) and the speed-of-processing intervention for speed-of-processing performance (effect size = 0.62, 99% CI=0.31-0.93).
ConclusionEach Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention resulted in less decline in self-reported IADL compared with the control group. Reasoning and speed, but not memory, training resulted in improved targeted cognitive abilities for 10 years.
C1 [Rebok, George W.] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD 21205 USA.
[Rebok, George W.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
[Ball, Karlene] Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA.
[Guey, Lin T.; Kim, Hae-Young; Tennstedt, Sharon L.] New England Res Inst, Watertown, MA 02172 USA.
[Jones, Richard N.; Morris, John N.] Hebrew SeniorLife, Social & Hlth Policy Res, Boston, MA USA.
[King, Jonathan W.] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA.
[Marsiske, Michael] Univ Florida, Inst Aging, Gainesville, FL USA.
[Marsiske, Michael] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA.
[Unverzagt, Frederick W.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Willis, Sherry L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Rebok, GW (reprint author), Johns Hopkins Univ, Dept Mental Hlth, Hampton House 891,624 North Broadway, Baltimore, MD 21205 USA.
EM grebok@jhsph.edu
RI Jones, Richard/J-3488-2013;
OI Jones, Richard/0000-0002-1049-218X; Marsiske,
Michael/0000-0001-5973-2116
FU National Institute on Aging; National Institute of Nursing Research to
Hebrew Senior Life [U01 NR04507]; Indiana University School of Medicine
[U01NR04508]; Johns Hopkins University [U01AG14260]; New England
Research Institute [U01 AG14282]; Pennsylvania State University [U01
AG14263]; University of Alabama at Birmingham [U01 AG14289]; University
of Florida [U01AG14276]; Posit Science, Inc.; Robert Wood Johnson
Foundation; McKnight Brain Research Foundation; National Academy of
Neuropsychology
FX ACTIVE is supported by grants from the National Institute on Aging and
the National Institute of Nursing Research to Hebrew Senior Life (U01
NR04507), Indiana University School of Medicine (U01NR04508), Johns
Hopkins University (U01AG14260), New England Research Institute (U01
AG14282), Pennsylvania State University (U01 AG14263), University of
Alabama at Birmingham (U01 AG14289), and University of Florida
(U01AG14276). Drs. Unverzagt and Marsiske have received research support
from Posit Science, Inc., in the form of site licenses for cognitive
training programs for investigator-initiated research projects. Dr.
Marsiske has received research support from Robert Wood Johnson
Foundation and McKnight Brain Research Foundation and payment for
development of education presentations from the National Academy of
Neuropsychology and the International Neuropsychological Society for
workshops on cognitive interventions and from the National Institute on
Aging and American Society on Aging for overview presentation on
cognitive interventions. Dr. Ball is a consultant and owns stock in the
Visual Awareness Research Group and Posit Science, Inc., the companies
that market the UFOV Test and speed-ofprocessing training software, now
called Insight (the Visual Awareness Research Group invented Insight and
the UFOV). Dr. Ball serves as a member of the Posit Science Scientific
Advisory Board. Posit Science paid royalties to the Visual Awareness
Research Group (unrelated to the study described). The Visual Awareness
Research Group is an S Corp; all profits and losses flow to
stockholders. Dr. Rebok is an investigator with Compact Disc
Incorporated for the development of an electronic version of the ACTIVE
memory intervention. Drs. Morris and Jones received support from the
Edward Fein Foundation and Vicki and Arthur Loring for research
activities. The views expressed in this article are those of the authors
and not to be ascribed to the National Institute on Aging, National
Institute of Nursing Research or the Department of Health and Human
Services.
NR 48
TC 114
Z9 119
U1 8
U2 88
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2014
VL 62
IS 1
BP 16
EP 24
DI 10.1111/jgs.12607
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 292AS
UT WOS:000329874600003
PM 24417410
ER
PT J
AU Ceresini, G
Ceda, GP
Lauretani, F
Maggio, M
Usberti, E
Marina, M
Bandinelli, S
Guralnik, JM
Valenti, G
Ferrucci, L
AF Ceresini, Graziano
Ceda, Gian P.
Lauretani, Fulvio
Maggio, Marcello
Usberti, Elisa
Marina, Michela
Bandinelli, Stefania
Guralnik, Jack M.
Valenti, Giorgio
Ferrucci, Luigi
TI LOW THYROTROPIN FROM NONTHYROIDAL ILLNESS? RESPONSE
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Letter
ID CHIANTI
C1 [Ceresini, Graziano; Ceda, Gian P.; Maggio, Marcello; Usberti, Elisa; Marina, Michela; Valenti, Giorgio] Univ Hosp Parma, Dept Clin & Expt Med, Geriatr Endocrine Unit, Parma, Italy.
[Lauretani, Fulvio] Univ Hosp Parma, Geriatr Unit, Parma, Italy.
[Bandinelli, Stefania] ASF Toscana, Geriatr Unit, Florence, Italy.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
RP Ceresini, G (reprint author), Univ Hosp Parma, Dept Clin & Expt Med, Geriatr Endocrine Unit, Parma, Italy.
NR 5
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2014
VL 62
IS 1
BP 208
EP 209
DI 10.1111/jgs.12616
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 292AS
UT WOS:000329874600041
PM 25180397
ER
PT J
AU Shen, QF
Yamano, K
Head, BP
Kawajiri, S
Cheung, JTM
Wang, CX
Cho, JH
Hattori, N
Youle, RJ
van der Bliek, AM
AF Shen, Qinfang
Yamano, Koji
Head, Brian P.
Kawajiri, Sumihiro
Cheung, Jesmine T. M.
Wang, Chunxin
Cho, Jeong-Hoon
Hattori, Nobutaka
Youle, Richard J.
van der Bliek, Alexander M.
TI Mutations in Fis1 disrupt orderly disposal of defective mitochondria
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID DYNAMIN-RELATED GTPASE; MAMMALIAN-CELLS; C-ELEGANS; FISSION MACHINERY;
PEROXISOMAL FISSION; PROTEIN DRP1; PARKIN; MEMBRANE; MITOPHAGY;
AUTOPHAGY
AB Mitochondrial fission is mediated by the dynamin-related protein Drp1 in metazoans. Drp1 is recruited from the cytosol to mitochondria by the mitochondrial outer membrane protein Mff. A second mitochondrial outer membrane protein, named Fis1, was previously proposed as recruitment factor, but Fis1(-/-) cells have mild or no mitochondrial fission defects. Here we show that Fis1 is nevertheless part of the mitochondrial fission complex in metazoan cells. During the fission cycle, Drp1 first binds to Mff on the surface of mitochondria, followed by entry into a complex that includes Fis1 and endoplasmic reticulum (ER) proteins at the ER-mitochondrial interface. Mutations in Fis1 do not normally affect fission, but they can disrupt downstream degradation events when specific mitochondrial toxins are used to induce fission. The disruptions caused by mutations in Fis1 lead to an accumulation of large LC3 aggregates. We conclude that Fis1 can act in sequence with Mff at the ER-mitochondrial interface to couple stress-induced mitochondrial fission with downstream degradation processes.
C1 [Shen, Qinfang; Head, Brian P.; Kawajiri, Sumihiro; Cheung, Jesmine T. M.; Cho, Jeong-Hoon; van der Bliek, Alexander M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA.
[Yamano, Koji; Wang, Chunxin; van der Bliek, Alexander M.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Kawajiri, Sumihiro; Hattori, Nobutaka] Juntendo Univ, Dept Neurol, Sch Med, Tokyo 1138421, Japan.
RP van der Bliek, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA.
EM avan@mednet.ucla.edu
RI Wang, Chunxin/B-9312-2016
OI Wang, Chunxin/0000-0001-6015-6806
FU National Institutes of Health [GM051866, T32-GM07104]; National Science
Foundation [0552271]; Naito Foundation; Nakatomi Foundation; Japan
Society for the Promotion of Science; Japan Society for the Promotion of
Science Fellowship for Research Abroad
FX We thank other members of the van der Bliek and Youle labs for helpful
discussions. Strains were provided by the Caenorhabditis Genetics Center
and S. Mitani. Technical support for electron microscopy was provided by
the National Institute of Neurological Disorders and Stroke EM Facility.
This work was supported by grants from the National Institutes of Health
(GM051866) and the National Science Foundation (0552271) to A.M.V.D.B.
B.P.H. received a National Institutes of Health Training Grant
(T32-GM07104). S.K. was supported by a fellowship from the Naito
Foundation and the Nakatomi Foundation. N.H. was supported by the Japan
Society for the Promotion of Science, and K.Y. was supported by a Japan
Society for the Promotion of Science Fellowship for Research Abroad.
NR 61
TC 42
Z9 44
U1 2
U2 11
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JAN 1
PY 2014
VL 25
IS 1
BP 145
EP 159
DI 10.1091/mbc.E13-09-0525
PG 15
WC Cell Biology
SC Cell Biology
GA 294DL
UT WOS:000330022500013
PM 24196833
ER
PT J
AU Chow, KH
Elgort, S
Dasso, M
Powers, MA
Ullman, KS
AF Chow, Kin-Hoe
Elgort, Suzanne
Dasso, Mary
Powers, Maureen A.
Ullman, Katharine S.
TI The SUMO proteases SENP1 and SENP2 play a critical role in nucleoporin
homeostasis and nuclear pore complex function
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID AXIN-BINDING PROTEIN; CELL-CYCLE; SUMOYLATION; PATHWAY; POM121;
ISOPEPTIDASE; TRANSPORT; UBIQUITIN; MEMBRANE; PHOSPHORYLATION
AB Nuclear pore complexes are composed of similar to 30 different proteins, each present at the pore in multiple copies. Together these proteins create specialized channels that convey cargo between the cytoplasm and the nuclear interior. With the building blocks of nuclear pores identified, one challenge is to decipher how these proteins are coordinately produced and assembled into macromolecular pore structures with each cell division. Specific individual pore proteins and protein cofactors have been probed for their role in the assembly process, as well as certain kinases that add a layer of regulation via the phosphorylation status of nucleoporins. Other posttranslational modifications are candidates for coordinating events of pore assembly as well. In this study of two pore-associated small ubiquitin-like modifier (SUMO) proteases, sentrin/SUMO-specific protease 1 (SENP1) and SENP2, we observe that many nucleoporins are mislocalized and, in some cases, reduced in level when SENP1 and SENP2 are codepleted. The pore complexes present under these conditions are still capable of transport, although the kinetics of specific cargo is altered. These results reveal a new role for the pore-associated SENPs in nucleoporin homeostasis and in achieving proper configuration of the nuclear pore complex.
C1 [Chow, Kin-Hoe; Elgort, Suzanne; Ullman, Katharine S.] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
[Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Powers, Maureen A.] Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA.
RP Ullman, KS (reprint author), Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT 84112 USA.
EM katharine.ullman@hci.utah.edu
OI Dasso, Mary/0000-0002-5410-1371
FU National Institutes of Health [R01 GM61275, RO1 GM059975]; National
Institute of Child Health and Human Development intramural funds [Z01
HD001902, Z01 HD008816]; [P30 CA042014]
FX We thank Douglass Forbes for providing antibodies. This work was
supported by National Institutes of Health Grants R01 GM61275 (K.U.) and
RO1 GM059975 (M.P.) and National Institute of Child Health and Human
Development intramural funds (Projects Z01 HD001902 and Z01 HD008816 to
M.D.). Shared resources used in this project are supported in part by
P30 CA042014 awarded to the Huntsman Cancer Institute.
NR 67
TC 3
Z9 4
U1 1
U2 6
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JAN 1
PY 2014
VL 25
IS 1
BP 160
EP 168
DI 10.1091/mbc.E13-05-0256
PG 9
WC Cell Biology
SC Cell Biology
GA 294DL
UT WOS:000330022500014
PM 24196834
ER
PT J
AU Parkhitko, AA
Priolo, C
Coloff, JL
Yun, J
Wu, JJ
Mizumura, K
Xu, WP
Malinowska, IA
Yu, J
Kwiatkowski, DJ
Locasale, JW
Asara, JM
Choi, AMK
Finkel, T
Henske, EP
AF Parkhitko, Andrey A.
Priolo, Carmen
Coloff, Jonathan L.
Yun, Jihye
Wu, Julia J.
Mizumura, Kenji
Xu, Wenping
Malinowska, Izabela A.
Yu, Jane
Kwiatkowski, David J.
Locasale, Jason W.
Asara, John M.
Choi, Augustine M. K.
Finkel, Toren
Henske, Elizabeth P.
TI Autophagy-Dependent Metabolic Reprogramming Sensitizes TSC2-Deficient
Cells to the Antimetabolite 6-Aminonicotinamide
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; ANTITUMOR-ACTIVITY; CANCER; ACTIVATION
AB The mammalian target of rapamycin complex 1 (mTORC1) is hyperactive in many human cancers and in tuberous sclerosis complex (TSC). Autophagy, a key mTORC1-targeted process, is a critical determinant of metabolic homeostasis. Metabolomic profiling was performed to elucidate the cellular consequences of autophagy dysregulation under conditions of hyperactive mTORC1. It was discovered that TSC2-null cells have distinctive autophagy-dependent pentose phosphate pathway (PPP) alterations. This was accompanied by enhanced glucose uptake and utilization, decreased mitochondrial oxygen consumption, and increased mitochondrial reactive oxygen species (ROS) production. Importantly, these findings revealed that the PPP is a key autophagy-dependent compensatory metabolic mechanism. Furthermore, PPP inhibition with 6-aminonicotinamide (6-AN) in combination with autophagy inhibition suppressed proliferation and prompted the activation of NF-kappa B and CASP1 in TSC2-deficient, but not TSC2-proficient cells. These data demonstrate that TSC2-deficient cells can be therapeutically targeted, without mTORC1 inhibitors, by focusing on their metabolic vulnerabilities.
C1 [Parkhitko, Andrey A.; Priolo, Carmen; Mizumura, Kenji; Xu, Wenping; Yu, Jane; Choi, Augustine M. K.; Henske, Elizabeth P.] Harvard Univ, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Malinowska, Izabela A.; Kwiatkowski, David J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Translat Med, Boston, MA 02115 USA.
[Coloff, Jonathan L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
[Parkhitko, Andrey A.; Priolo, Carmen; Coloff, Jonathan L.; Yun, Jihye; Mizumura, Kenji; Xu, Wenping; Malinowska, Izabela A.; Yu, Jane; Kwiatkowski, David J.; Asara, John M.; Choi, Augustine M. K.; Henske, Elizabeth P.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Yun, Jihye; Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA.
[Wu, Julia J.; Finkel, Toren] NHLBI, Bethesda, MD USA.
[Parkhitko, Andrey A.] Russian State Med Univ, Moscow 117437, Russia.
[Locasale, Jason W.] Cornell Univ, Div Nutr Sci, New York, NY 10021 USA.
RP Priolo, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 1 Blackfan Circle, Boston, MA 02115 USA.
EM ehenske@partners.org
OI Locasale, Jason/0000-0002-7766-3502
FU LAM Foundation; Adler Foundation; Tuberous Sclerosis Alliance; National
Institute of Diabetes and Digestive and Kidney Diseases; NIH
[5P01CA120964-04]; NIH DF/HCC; Cancer Center [P30CA006516-46]; National
Heart, Lung, and Blood Institute; National Cancer Institute
FX This work was supported by the LAM Foundation, the Adler Foundation, the
Tuberous Sclerosis Alliance, the National Institute of Diabetes and
Digestive and Kidney Diseases (to E.P. Henske); grants NIH
5P01CA120964-04 and NIH DF/HCC, Cancer Center Support Grant
P30CA006516-46 (to J.M. Asara); the National Heart, Lung, and Blood
Institute (to J.J. Yu); and the National Cancer Institute (to D.J.
Kwiatkowski).
NR 22
TC 11
Z9 11
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
EI 1557-3125
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JAN
PY 2014
VL 12
IS 1
BP 48
EP 57
DI 10.1158/1541-7786.MCR-13-0258-T
PG 10
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 292RL
UT WOS:000329919800006
PM 24296756
ER
PT J
AU Postnikov, YV
Furusawa, T
Haines, DC
Factor, VM
Bustin, M
AF Postnikov, Yuri V.
Furusawa, Takashi
Haines, Diana C.
Factor, Valentina M.
Bustin, Michael
TI Loss of the Nucleosome-Binding Protein HMGN1 Affects the Rate of
N-Nitrosodiethylamine-Induced Hepatocarcinogenesis in Mice
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID FATTY LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; HEPATIC CARCINOGENESIS;
DNA-REPAIR; CHROMATIN; CANCER; PHOSPHORYLATION; INFLAMMATION;
EPIGENOMICS; ACTIVATION
AB We report that HMGN1, a nucleosome-binding protein that affects chromatin structure and function, affects the growth of N-nitrosodiethylamine (DEN)-induced liver tumors. Following a single DENinjection at 2 weeks of age, Hmgn1(tm1/tm1) mice, lacking the nucleosome-binding domain of HMGN1, had earlier signs of liver tumorigenesis than their Hmgn1(+/+) littermates. Detailed gene expression profiling revealed significant differences between DEN-injected and control saline-injected mice, but only minor differences between the injected Hmgn1(tm1/tm1) mice and their Hmgn1(+/+) littermates. Pathway analysis revealed that the most significant process affected by loss of HMGN1 involves the lipid/sterol metabolic pathway. Our study indicates that in mice, loss of HMGN1 leads to transcription changes that accelerate the progression of DEN-induced hepatocarcinogenesis, without affecting the type of tumors or the final total tumor burden of these mice.
C1 [Postnikov, Yuri V.; Furusawa, Takashi; Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Factor, Valentina M.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Haines, Diana C.] NCI, Sci Applicat Int Corp, NIH, Bethesda, MD 20892 USA.
RP Postnikov, YV (reprint author), NIH, 37 Convent Dr 3122, Bethesda, MD 20892 USA.
EM postniky@mail.nih.gov
RI Bustin, Michael/G-6155-2015
FU Center for Cancer Research; Intramural Research Program at the NIH,
National Cancer Institute; National Cancer Institute, NIH
[HHSN261200800001E]
FX The research was supported by the Center for Cancer Research, The
Intramural Research Program at the NIH, National Cancer Institute, and
with funds from the National Cancer Institute, NIH, under Contract No.
HHSN261200800001E.
NR 31
TC 3
Z9 3
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
EI 1557-3125
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD JAN
PY 2014
VL 12
IS 1
BP 82
EP 90
DI 10.1158/1541-7786.MCR-13-0392
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 292RL
UT WOS:000329919800009
PM 24296759
ER
PT S
AU Thurin, M
Marincola, FM
AF Thurin, Magdalena
Marincola, Francesco M.
BE Thurin, M
Marincola, FM
TI Molecular Diagnostics for Melanoma Methods and Protocols Preface
SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Editorial Material; Book Chapter
AB A new taxonomy of cancers defined by molecular signatures with prognostic and therapeutic implications is emerging. Pathological assessment of melanoma that is the current standard method to determine diagnosis is improving due to additional criteria evolving from understanding of biology of melanoma. Genomics, epigenomics, and proteomics approaches have already led to molecular reclassification of melanoma in the context with pathological findings. Moreover, discovery of genetic alterations that drive melanoma progression provide the basis for the development of targeted therapies for patients with metastatic disease. Following these discoveries, the U.S. Food and Drug Administration (FDA) approved in 2011 and 2013 small molecular compounds vemurafenib and dabrafenib, respectively, that provide novel treatment options for melanoma patients. Vemurafenib and dabrafenib target mutated V600 codon of BRAF signaling molecule that is a key effector of RAS/RAF/MEK/ERK pathway. Mutations in this gene occur in over half of melanoma tumors and BRAF V600E mutations are the most common. Additional agent targeting downstream MAPK kinases including MEK1/2 inhibitor, trametinib was also approved by the FDA in 2013. Concomitantly with these drugs, companion diagnostic tests for detection of BRAF V600 mutations were also approved. These tests can identify specific subpopulations of melanoma patients with BRAF V600 codon mutations who most likely will benefit from the therapy. These examples are a prototype of a broad category of personalized treatment that uses a companion test to select patients for specifi c treatment.
Recent, promising approaches to improve responses in melanoma by blocking negative regulators of T cell activity, i.e., cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) receptors were demonstrated and anti-CTLA drug ipilimumab was approved by the FDA in 2011. While there are no approved diagnostics for immunotherapy, promising markers associated with response to ipilimumab and anti-PD1 therapy were identified. Given that the majority of patients do not respond to these drugs and drugs are highly toxic, predictive markers could potentially improve therapeutic ratio of these drugs.
The primary purpose of this volume is to provide updated information on well-characterized diagnostic and prognostic assays and assays predicting response to treatment for routine testing. The focus is also on a few emerging biomarkers categories with potential clinical validity rather than on early discovery stage. Most of chapters provide detailed protocols for markers' detection and novel technologies with potential for clinical application. Several review chapters provide an overview of the current status in diagnosis and therapy of melanoma and discuss the need to incorporate biomarkers to impact patient care. Important issues related to marker development and validation such as statistical approaches and specimen requirements are also discussed.
C1 [Thurin, Magdalena] NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] Qatar Fdn, Sidra Med & Res Ctr, Doha, Qatar.
RP Thurin, M (reprint author), NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
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 978-1-62703-726-6; 978-1-62703-727-3
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1102
BP V
EP XIV
D2 10.1007/978-1-62703-727-3
PG 10
WC Oncology
SC Oncology
GA BJM68
UT WOS:000329172000001
ER
PT S
AU Lau, C
Killian, KJ
Samuels, Y
Rudloff, U
AF Lau, Christopher
Killian, Keith J.
Samuels, Yardena
Rudloff, Udo
BE Thurin, M
Marincola, FM
TI ERBB4 Mutation Analysis: Emerging Molecular Target for Melanoma
Treatment
SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Metastatic melanoma; Genomic landscape; Somatic mutations; DNA
isolation; Sanger sequencing; ERBB4 gene; Marker predictive for
treatment; Mutation validation; Treatment target
ID EPIDERMAL-GROWTH-FACTOR; IMPROVED SURVIVAL; CRYSTAL-STRUCTURE; FAMILY
REVEALS; CANCER; GENOME; METALLOPROTEINASE; INHIBITION; CELLS; TRIAL
AB Recent sequencing efforts in melanoma have elucidated many previously unknown molecular pathways and biological mechanisms involved in melanoma development and progression and have yielded a number of promising targets for molecular therapy. As sequencing technologies have become more sophisticated and have revealed an ever-increasing complexity of the genetic landscape of melanoma, it has become clear that sequencing methods applied to clinical specimens have to reliably capture not only recurrent "hotspot" mutations like BRAFV600 and NRASQ61 or "mini-hotspot" mutations like exon 11 and 13 c-KIT but also heterogeneous somatic mutations dispersed across multiple functionally conserved regions of genes or entire genes. One such example in melanoma is the ERBB4 receptor, or HER4, a member of the Erb receptor family, which has recently been shown to be a major oncogenic "driver" in melanoma. Mutated ERBB4 signaling activates both aberrant ERBB4 and PI3K-AKT signal transduction, mediates sensitivity to small-molecule inhibition with the dual-tyrosine kinase inhibitor lapatinib, and has recently also been implied in oncogenic glutamatergic signaling in melanoma. Mutations involving the ERBB4 gene act as "gain-of-function" mutations and predominantly involve the extracellular domains of the receptor. Additional sequencing efforts have recently identified recurrent mutations ("mini-hotspots") or mutation clusters which affect the regulation of, e. g., ligand binding, arrangement of extracellular domain alignment, or intramolecular tether formation.
In this chapter, we describe the methods used to determine the mutation status of all exons of the ERBB4 gene in clinical specimens obtained from patients afflicted by metastatic melanoma. Upon slight modifications, this protocol can also be used for mutational analysis of other oncogenes affected by "non-hotspot" mutations dispersed across multiple exons. This sequencing technique has successfully been applied within a clinical trial selecting patients with ERBB4-mutant melanoma for lapatinib treatment. With the increasing emergence of low-frequency oncogenes affected by heterogeneous activating mutations located in different exons and regions this method will provide a mean to translate the promise of recently obtained genetic knowledge into clinical genotype-directed targeted therapy trials.
C1 [Lau, Christopher; Killian, Keith J.] NCI, Clin Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Rudloff, Udo] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lau, C (reprint author), NCI, Clin Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
FU European Research Council [335377]
NR 37
TC 3
Z9 3
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 978-1-62703-726-6; 978-1-62703-727-3
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1102
BP 461
EP 480
DI 10.1007/978-1-62703-727-3_24
D2 10.1007/978-1-62703-727-3
PG 20
WC Oncology
SC Oncology
GA BJM68
UT WOS:000329172000025
PM 24258993
ER
PT S
AU Quackenbush, JF
Cassidy, PB
Pfeffer, LM
Boucher, KM
Hawkes, JE
Pfeffer, SR
Kopelovich, L
Leachman, SA
AF Quackenbush, John F.
Cassidy, Pamela B.
Pfeffer, Lawrence M.
Boucher, Kenneth M.
Hawkes, Jason E.
Pfeffer, Susan R.
Kopelovich, Levy
Leachman, Sancy A.
BE Thurin, M
Marincola, FM
TI Isolation of Circulating MicroRNAs from Microvesicles Found in Human
Plasma
SO MOLECULAR DIAGNOSTICS FOR MELANOMA: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE MicroRNA; Microvesicles; Plasma; Serum; ExoQuick
ID FAMILIAL MELANOMA; GENE-EXPRESSION; RNA
AB Intact miRNAs can be isolated from the circulation in significant quantities despite the presence of extremely high levels of RNase activity. The remarkable stability of circulating miRNAs makes them excellent candidates for biomarkers in diagnostic applications as well as therapeutic targets in a variety of disease states including melanoma. Circulating RNA molecules are resistant to degradation by RNases because they are encapsulated in membrane-bound microvesicles. We describe a convenient method for the use of ExoQuick, a proprietary resin developed by Systems Biosciences (Mountain View, CA), whereby microvesicles can be purified under gentle conditions using readily available laboratory equipment. This protocol allows for isolation all microvesicles, regardless of their origin, and provides a convenient method for identifying potential cancer-specific biomarkers from biological fluids including serum and plasma.
C1 [Quackenbush, John F.; Boucher, Kenneth M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Cassidy, Pamela B.; Leachman, Sancy A.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA.
[Pfeffer, Lawrence M.; Pfeffer, Susan R.] Univ Tennessee Hlth Sci Ctr, Dept Pathol, Memphis, TN USA.
[Hawkes, Jason E.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Rockville, MD USA.
RP Quackenbush, JF (reprint author), Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
OI Boucher, Kenneth/0000-0003-2833-0127; Hawkes, Jason
E./0000-0001-5870-181X
FU NCI NIH HHS [5P30CA042014-23]; PHS HHS [N201143]
NR 23
TC 17
Z9 17
U1 1
U2 7
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-62703-726-6; 978-1-62703-727-3
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1102
BP 641
EP 653
DI 10.1007/978-1-62703-727-3_34
D2 10.1007/978-1-62703-727-3
PG 13
WC Oncology
SC Oncology
GA BJM68
UT WOS:000329172000035
PM 24259003
ER
PT J
AU Taylor, TN
Alter, SP
Wang, MZ
Goldstein, DS
Miller, GW
AF Taylor, Tonya N.
Alter, Shawn P.
Wang, Minzheng
Goldstein, David S.
Miller, Gary W.
TI Reduced vesicular storage of catecholamines causes progressive
degeneration in the locus ceruleus
SO NEUROPHARMACOLOGY
LA English
DT Article
DE VMAT2; Norepinephrine; Parkinson's disease; Locus ceruleus
ID PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; POLYCHLORINATED-BIPHENYLS;
IMMUNOCHEMICAL ANALYSIS; CYTOSOLIC DOPAMINE; STRIATAL DOPAMINE;
SUBSTANTIA-NIGRA; KNOCKOUT MICE; MOUSE MODEL; CELL LOSS
AB Parkinson's disease (PD) is the most common neurodegenerative motor disease. Pathologically, PD is characterized by Lewy body deposition and subsequent death of dopamine neurons in the substantia nigra pars compacta. PD also consistently features degeneration of the locus ceruleus, the main source of norepinephrine in the central nervous system. We have previously reported a mouse model of dopaminergic neurodegeneration based on reduced expression of the vesicular monoamine transporter (VMAT2 LO). To determine if reduced vesicular storage can also cause noradrenergic degeneration, we examined indices of damage to the catecholaminergic systems in brain and cardiac tissue of VMAT2 LO mice. At two months of age, neurochemical analyses revealed substantial reductions in striatal dopamine (94%), cortical dopamine (57%) and norepinephrine (54%), as well as cardiac norepinephrine (97%). These losses were accompanied by increased conversion of dopamine and norepinephrine to their deaminated metabolites. VMAT2 LO mice exhibited loss of noradrenergic innervation in the cortex, as determined by norepinephrine transporter immunoreactivity and H-3-nisoxetine binding. Using unbiased stereological techniques, we observed progressive degeneration in the locus ceruleus that preceded degeneration of the substantia nigra pars compacta. In contrast, the ventral tegmental area, which is spared in human PD, remained unaffected. The coordinate loss of dopamine and norepinephrine neurons in VMAT2 LO mice parallels the pattern of neurodegeneration that occurs in human PD, and demonstrates that insufficient catecholamine storage can cause spontaneous degeneration in susceptible neurons, underscoring cytosolic catecholamine catabolism as a determinant of neuronal susceptibility in PD. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Taylor, Tonya N.; Alter, Shawn P.; Wang, Minzheng; Miller, Gary W.] Ctr Neurodegenerat Dis, Atlanta, GA USA.
[Taylor, Tonya N.; Alter, Shawn P.; Wang, Minzheng; Miller, Gary W.] Emory Univ, Dept Environm Hlth, Atlanta, GA 30322 USA.
[Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
RP Miller, GW (reprint author), Emory Univ, Dept Environm Hlth, 1518 Clifton Rd,Claudia Nance Rollins 8007, Atlanta, GA 30322 USA.
EM gary.miller@emory.edu
OI Miller, Gary/0000-0001-8984-1284
FU [F31 ES017247]; [T32 ES012870]; [T32 GM008602]; [P50 NS071669]; [P01
ES01673]
FX This work was supported by funding from F31 ES017247 (Taylor), T32
ES012870, T32 GM008602 (Alter), P50 NS071669 and P01 ES01673 (Miller).
The authors are grateful for the technical assistance provided by
Patricia Sullivan in acquisition of HPLC data. We would like to thank
Dr. Alison Bernstein for generating and characterizing the VMAT2
antibody.
NR 61
TC 18
Z9 18
U1 0
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 97
EP 105
DI 10.1016/j.neuropharm.2013.08.033
PN A
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YI
UT WOS:000330083400010
PM 24025942
ER
PT J
AU Hall, FS
Itokawa, K
Schmitt, A
Moessner, R
Sora, I
Lesch, KP
Uhl, GR
AF Hall, F. S.
Itokawa, K.
Schmitt, A.
Moessner, R.
Sora, I.
Lesch, K. P.
Uhl, G. R.
TI Decreased vesicular monoamine transporter 2 (VMAT2) and dopamine
transporter (DAT) function in knockout mice affects aging of
dopaminergic systems
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Transgenic mice; Gene knockout; Dopamine; Aging; Amphetamine; Cocaine
ID AGE-RELATED DECLINE; PARKINSONISM-INDUCING NEUROTOXIN;
POSITRON-EMISSION-TOMOGRAPHY; VESICLE AMINE TRANSPORTER; LONG-EVANS
RATS; STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; IN-VIVO; OXIDATIVE STRESS;
COCAINE REWARD
AB Dopamine (DA) is accumulated and compartmentalized by the dopamine transporter (DAT; SLOA6) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2). These transporters work at the plasma and vesicular membranes of dopaminergic neurons, respectively, and thus regulate levels of DA in neuronal compartments that include the extravesicular cytoplasmic compartment. DA in this compartment has been hypothesized to contribute to oxidative damage that can reduce the function of dopaminergic neurons in aging brains and may contribute to reductions in dopaminergic neurochemical markers, locomotor behavior and responses to dopaminergic drugs that are found in aged animals. The studies reported here examined aged mice with heterozygous deletions of VMAT2 or of DAT, which each reduce transporter expression to about 50% of levels found in wild-type (WT) mice. Aged mice displayed reduced locomotor responses under a variety of circumstances, including in response to locomotor stimulants, as well as changes in monoamine levels and metabolites in a regionally dependent manner. Several effects of aging were more pronounced in heterozygous VMAT2 knockout (KO) mice, including aging induced reductions in locomotion and reduced locomotor responses to cocaine. By contrast, some effects of aging were reduced or not observed in heterozygous DAT KO mice. These findings support the idea that altered DAT and VMAT2 expression affect age-related changes in dopaminergic function. These effects are most likely mediated by alterations in DA compartmentalization, and might be hypothesized to be exacerbated by other factors that affect the metabolism of cytosolic DA. (C) Published by Elsevier Ltd.
C1 [Hall, F. S.; Uhl, G. R.] NIDA, NIH, DHHS, Mol Neurobiol Branch,Intramural Res Program, Baltimore, MD 21224 USA.
[Itokawa, K.] Saitama Med Sch, Dept Neurol, Saitama, Japan.
[Schmitt, A.; Moessner, R.; Lesch, K. P.] Univ Wurzburg, Dept Psychiat, Wurzburg, Germany.
[Sora, I.] Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 980, Japan.
RP Hall, FS (reprint author), NIDA, IRP, Mol Neurobiol Branch, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM shall@intra.nida.nih.gov
RI Lesch, Klaus-Peter/J-4906-2013; Hall, Frank/C-3036-2013
OI Lesch, Klaus-Peter/0000-0001-8348-153X; Hall, Frank/0000-0002-0822-4063
FU Intramural Research Program of the National Institute on Drug Abuse
(NIH/DHHS); Deutsche Forschungsgemeinschaft [SFB 581, KFO 125/1-2];
European Commission [NEWMOOD LSHM-CT-2003-503474]
FX The authors are grateful for the expert technical assistance of T.
Heinemann and R. Burger, and the financial support of the Intramural
Research Program of the National Institute on Drug Abuse (NIH/DHHS), the
Deutsche Forschungsgemeinschaft (SFB 581, KFO 125/1-2) and the European
Commission (NEWMOOD LSHM-CT-2003-503474). The authors declare that there
exist no conflicts of interest with regard to the publication of this
work.
NR 115
TC 7
Z9 7
U1 2
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 146
EP 155
DI 10.1016/j.neuropharm.2013.07.031
PN A
PG 10
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YI
UT WOS:000330083400015
PM 23978383
ER
PT J
AU Shurtleff, D
Sasek, C
Kautz, M
AF Shurtleff, David
Sasek, Cathrine
Kautz, Mary
TI Sponsor's foreword: NIDA at forty Foreword
SO NEUROPHARMACOLOGY
LA English
DT Editorial Material
ID DRUG-ADDICTION; NEUROBIOLOGICAL MECHANISMS; SMOKING-CESSATION; COCAINE
ADDICTION; REWARD; VULNERABILITY; RECEPTOR; FUTURE; ABUSE; MODEL
C1 [Shurtleff, David; Sasek, Cathrine; Kautz, Mary] NIDA, NIH, Bethesda, MD 20892 USA.
RP Sasek, C (reprint author), NIDA, Off Sci Policy & Commun, 6001 Execut Blvd,Rm 5230,MSC 9991, Bethesda, MD 20892 USA.
EM csasek@nih.gov
NR 37
TC 0
Z9 0
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 195
EP 197
DI 10.1016/j.neuropharm.2013.08.020
PN B
PG 3
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YK
UT WOS:000330083600001
PM 23994442
ER
PT J
AU Volkow, ND
Baler, RD
AF Volkow, N. D.
Baler, R. D.
TI Addiction science: Uncovering neurobiological complexity
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Addiction; SUD; Dopamine; Nucleus accumbens; Brain imaging; Reward
ID VENTRAL TEGMENTAL AREA; CATECHOL-O-METHYLTRANSFERASE; COCAINE-SEEKING
BEHAVIOR; GENOME-WIDE ASSOCIATION; NICOTINE REPLACEMENT THERAPY;
SUCCESSFUL SMOKING-CESSATION; ALCOHOL-DEPENDENT PATIENTS; MEDIAL
PREFRONTAL CORTEX; INDUCED DOPAMINE RELEASE; PITUITARY-ADRENAL AXIS
AB Until very recently addiction-research was limited by existing tools and strategies that were inadequate for studying the inherent complexity at each of the different phenomenological levels. However, powerful new tools (e.g., optogenetics and designer drug receptors) and high throughput protocols are starting to give researchers the potential to systematically interrogate "all" genes, epigenetic marks, and neuronal circuits. These advances, combined with imaging technologies (both for preclinical and clinical studies) and a paradigm shift toward open access have spurred an unlimited growth of datasets transforming the way we investigate the neurobiology of substance use disorders (SUD) and the factors that modulate risk and resilience. Published by Elsevier Ltd.
C1 [Volkow, N. D.; Baler, R. D.] NIDA, NIH, Bethesda, MD 20892 USA.
RP Volkow, ND (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA.
EM nvokow1@nida.nih.gov
FU Intramural NIH HHS [ZIA AA000550-09]
NR 245
TC 53
Z9 57
U1 5
U2 65
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 235
EP 249
DI 10.1016/j.neuropharm.2013.05.007
PN B
PG 15
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YK
UT WOS:000330083600006
PM 23688927
ER
PT J
AU Ikemoto, S
Bonci, A
AF Ikemoto, Satoshi
Bonci, Antonello
TI Neurocircuitry of drug reward
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Drug reward; Motivation; Emotion; Dopamine; Ventral tegmental area;
Ventral striatum; Supramammillary nucleus; Median raphe nucleus
ID VENTRAL TEGMENTAL AREA; MEDIAN RAPHE NUCLEUS; CONDITIONED PLACE
PREFERENCE; MESOLIMBIC DOPAMINE SYSTEM; FREELY MOVING RATS; C-FOS
EXPRESSION; OLFACTORY TUBERCLE; SUPRAMAMMILLARY NUCLEUS;
LOCOMOTOR-ACTIVITY; SELF-STIMULATION
AB In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. Published by Elsevier Ltd.
C1 [Ikemoto, Satoshi; Bonci, Antonello] NIDA, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA.
[Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Neurosci Inst, Baltimore, MD 21205 USA.
RP Ikemoto, S (reprint author), NIDA, Intramural Res Program, NIH, US Dept Hlth & Human Serv, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM satoshi.ikemoto@nih.gov; antonello.bonci@nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU intramural Research Program of National Institute of Drug Abuse,
National Institutes of Health
FX The present work is supported by the intramural Research Program of
National Institute of Drug Abuse, National Institutes of Health.
NR 141
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 329
EP 341
DI 10.1016/j.neuropharm.2013.04.031
PN B
PG 13
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YK
UT WOS:000330083600014
PM 23664810
ER
PT J
AU Calu, DJ
Chen, YW
Kawa, AB
Nair, SG
Shaham, Y
AF Calu, Donna J.
Chen, Yu-Wei
Kawa, Alex B.
Nair, Sunila G.
Shaham, Yavin
TI The use of the reinstatement model to study relapse to palatable food
seeking during dieting
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Food; Relapse; Stress; Priming; cue; Reinstatement; Dieting;
Self-administration
ID MELANIN-CONCENTRATING HORMONE; STRESS-INDUCED REINSTATEMENT;
CORTICOTROPIN-RELEASING-FACTOR; COCAINE-INDUCED REINSTATEMENT;
ANXIOGENIC DRUG YOHIMBINE; CUE-INDUCED REINSTATEMENT; CONDITIONED PLACE
PREFERENCE; ANTAGONIST SNAP 94847; RECEPTOR ANTAGONIST; PREFRONTAL
CORTEX
AB Excessive consumption of unhealthy foods is a major public health problem. While many people attempt to control their food intake through dieting, many relapse to unhealthy eating habits within a few months. We have begun to study this clinical condition in rats by adapting the reinstatement model, which has been used extensively to study relapse to drug seeking. In our adaptation of the relapse model, reinstatement of palatable food seeking by exposure to food-pellet priming, food-associated cues, or stress is assessed in food-restricted (to mimic dieting) rats after operant food-pellet self-administration training and subsequent extinction of the food-reinforced responding.
In this review, we first outline the clinical problem and discuss a recent study in which we assessed the predictive validity of the reinstatement model for studying relapse to food seeking during dieting by using the anorexigenic drug fenfluramine. Next, we summarize results from our initial studies on the role of several stress- and feeding-related peptides (corticotropin-releasing factor, hypocretin, melanin-concentrating hormone, peptide YY3-36) in reinstatement of palatable food seeking. We then present results from our studies on the role of dopamine and medial prefrontal cortex in stress-induced reinstatement of food seeking. We conclude by discussing potential clinical implications.
We offer two main conclusions: (1) the food reinstatement model is a simple, reliable, and valid model to study mechanisms of relapse to palatable food seeking during dieting, and to identify medications to prevent this relapse; (2) mechanisms of relapse to food seeking are often dissociable from mechanisms of ongoing food intake. Published by Elsevier Ltd.
C1 [Calu, Donna J.; Chen, Yu-Wei; Kawa, Alex B.; Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Nair, Sunila G.] Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA.
RP Calu, DJ (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM yshaham@intra.nida.nih.gov; yshaham@intra.nida.nih.gov
RI shaham, yavin/G-1306-2014;
OI Calu, Donna/0000-0003-2377-9494
FU National Institute on Drug Abuse, Intramural Research Program
FX Preparation of this review was supported by the National Institute on
Drug Abuse, Intramural Research Program. The authors declare that they
do not have any conflicts of interest (financial or otherwise) related
to the data presented in this manuscript.
NR 152
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 395
EP 406
DI 10.1016/j.neuropharm.2013.04.030
PN B
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YK
UT WOS:000330083600020
PM 23660229
ER
PT J
AU Lucantonio, F
Caprioli, D
Schoenbaum, G
AF Lucantonio, Federica
Caprioli, Daniele
Schoenbaum, Geoffrey
TI Transition from 'model-based' to 'model-free' behavioral control in
addiction: Involvement of the orbitofrontal cortex and dorsolateral
striatum
SO NEUROPHARMACOLOGY
LA English
DT Review
DE Addiction; Orbitofrontal cortex; Striatum
ID VENTROMEDIAL PREFRONTAL CORTEX; TEMPORAL DIFFERENCE MODELS; BASOLATERAL
AMYGDALA; DECISION-MAKING; DORSAL STRIATUM; AMPHETAMINE EXPOSURE;
DRUG-ADDICTION; HUMAN BRAIN; REPEATED PRETREATMENT; COCAINE EXPOSURE
AB Cocaine addiction is a complex and multidimensional process involving a number of behavioral and neural forms of plasticity. The behavioral transition from voluntary drug use to compulsive drug taking may be explained at the neural level by drug-induced changes in function or interaction between a flexible planning system, associated with prefrontal cortical regions, and a rigid habit system, associated with the striatum. The dichotomy between these two systems is operationalized in computational theory by positing model-based and model-free learning mechanisms, the former relying on an "internal model" of the environment and the latter on pre-computed or cached values to control behavior. In this review, we will suggest that model-free and model-based learning mechanisms appear to be differentially affected, at least in the case of psychostimulants such as cocaine, with the former being enhanced while the latter are disrupted. As a result, the behavior of long-term drug users becomes less flexible and responsive to the desirability of expected outcomes and more habitual, based on the long history of reinforcement. To support our specific proposal, we will review recent neural and behavioral evidence on the effect of psychostimulant exposure on orbitofrontal and dorsolateral striatum structure and function. Published by Elsevier Ltd.
C1 [Lucantonio, Federica] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Lucantonio, Federica; Schoenbaum, Geoffrey] NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
[Caprioli, Daniele] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
[Caprioli, Daniele] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England.
RP Schoenbaum, G (reprint author), NIDA, Intramural Res Program, Baltimore, MD 21224 USA.
EM geoffrey.schoenbaum@nih.gov
FU NIDA
FX The work of writing it was supported by funding from the intramural
programs of NIDA. Correspondence should be addressed to G.S.
(schoenbaumgm@nida.nih.gov).
NR 94
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JAN
PY 2014
VL 76
SI SI
BP 407
EP 415
DI 10.1016/j.neuropharm.2013.05.033
PN B
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 294YK
UT WOS:000330083600021
PM 23752095
ER
PT S
AU Wang, YJ
Chan, CC
AF Wang, Yujuan
Chan, Chi-Chao
BE Singh, AD
TI Ocular and Adnexal T-Cell Lymphoma
SO OCULAR AND ADNEXAL LYMPHOMA
SE Essentials in Ophthalmology
LA English
DT Article; Book Chapter
ID EPSTEIN-BARR-VIRUS; PRIMARY INTRAOCULAR LYMPHOMA; PRIMARY VITREORETINAL
LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; NON-HODGKINS-LYMPHOMA; ACUTE
LYMPHOBLASTIC-LEUKEMIA; OF-THE-LITERATURE; PERIPHERAL T;
CLINICOPATHOLOGICAL FEATURES; INTRAVITREAL METHOTREXATE
C1 [Wang, Yujuan; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Yujuan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM yujuan.wang@nih.gov; chanc@nei.nih.gov
NR 117
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U1 0
U2 0
PU SPRINGER-VERLAG BERLIN
PI BERLIN
PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY
SN 1612-3212
BN 978-3-642-38498-1; 978-3-642-38499-8
J9 ESSENT OPHTHALMOL
PY 2014
BP 103
EP 115
DI 10.1007/978-3-642-38499-8_10
D2 10.1007/978-3-642-38499-8
PG 13
WC Oncology; Ophthalmology
SC Oncology; Ophthalmology
GA BJM43
UT WOS:000329099500011
ER
PT J
AU LoBiondo-Wood, G
Brown, CG
Knobf, MT
Lyon, D
Mallory, G
Mitchell, SA
Von Ah, D
Wesmiller, S
Fellman, B
AF LoBiondo-Wood, Geri
Brown, Carlton G.
Knobf, M. Tish
Lyon, Debra
Mallory, Gail
Mitchell, Sandra A.
Von Ah, Diane
Wesmiller, Susan
Fellman, Bryan
TI Priorities for Oncology Nursing Research: The 2013 National Survey
SO ONCOLOGY NURSING FORUM
LA English
DT Article
DE evidence-based practice; clinical practice
ID BREAST-CANCER SURVIVORS; COGNITIVE IMPAIRMENT; CLINICAL ONCOLOGY;
AMERICAN SOCIETY; CARE; CHEMOTHERAPY; PREVENTION; STATEMENT; CHOICES;
IMPACT
AB Purpose/Objectives: To advance the goals of evidence-based care and prioritize the knowledge generation that addresses contemporary challenges in oncology nursing. Results are used to inform the development of the Oncology Nursing Society (ONS) Research Agenda and by the ONS Foundation to develop strategic research initiatives.
Design: Descriptive, cross-sectional survey.
Setting: Web-based survey.
Sample: 8,554 ONS members from all levels of education. All doctorally prepared members were invited to participate. A random stratified sample was obtained from the remainder of the membership.
Methods: The ONS Research Priorities Survey project team created the survey and analyzed and interpreted the results. Members received an email invitation and follow-up reminders for survey completion.
Main Research Variables: Oncology nursing research and evidence-based practice topic questions.
Findings: The response rate was 11%, which is comparable to previous surveys. Topics ranked included descriptive research on patient adherence; intervention studies to optimize adherence, achieve concordance with cancer screening guidelines in minority populations, manage neurologic and cardiovascular late effects, and manage symptoms and symptom clusters; and studies to identify optimal delivery models for survivorship care. These findings have direct implications for translating existing evidence into practice and underscore the need for intervention research focused on improving patient-centered outcomes.
Conclusions: Results provide a broad assessment of member views regarding oncology research priorities. Given the response rate, additional strategies to encourage member participation will be considered.
Implications for Nursing: The results, together with the updates of the ONS Research Agenda, can guide ONS and ONS Foundation research and evidence-based practice initiatives.
C1 [LoBiondo-Wood, Geri] Univ Texas Hlth Sci Ctr Houston, Sch Nursing, PhD Nursing Program, Houston, TX 77030 USA.
[Brown, Carlton G.] NYU, New York, NY USA.
[Knobf, M. Tish] Yale Univ, Sch Nursing, Acute Care & Hlth Syst Div, New Haven, CT 06536 USA.
[Lyon, Debra] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Mallory, Gail] Oncol Nursing Soc, Pittsburgh, PA USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Von Ah, Diane] Indiana Univ, Sch Nursing, Dept Sci Nursing Care, Indianapolis, IN 46204 USA.
[Wesmiller, Susan] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15260 USA.
[Fellman, Bryan] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
RP LoBiondo-Wood, G (reprint author), Univ Texas Hlth Sci Ctr Houston, Sch Nursing, PhD Nursing Program, Houston, TX 77030 USA.
EM geri.l.wood@uth.tmc.edu
FU NCI NIH HHS [P30 CA016672]; NINR NIH HHS [T32 NR011972]
NR 44
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Z9 9
U1 1
U2 7
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD JAN
PY 2014
VL 41
IS 1
BP 67
EP 76
DI 10.1188/14.ONF.67-76
PG 10
WC Oncology; Nursing
SC Oncology; Nursing
GA 292DK
UT WOS:000329882200013
PM 24368240
ER
PT S
AU Nielsen, PE
Appella, DH
AF Nielsen, Peter E.
Appella, Daniel H.
BE Nielsen, PE
Appella, DH
TI Peptide Nucleic Acids Methods and Protocols Second Edition Preface
SO PEPTIDE NUCLEIC ACIDS: METHODS AND PROTOCOLS, 2ND EDITION
SE Methods in Molecular Biology
LA English
DT Editorial Material; Book Chapter
C1 [Nielsen, Peter E.] Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, Copenhagen, Denmark.
[Appella, Daniel H.] NIDDK, Sect Synthet Bioact Mol, Bioorgan Chem Lab, NIH,DHHS, Bethesda, MD 20892 USA.
RP Nielsen, PE (reprint author), Univ Copenhagen, Fac Hlth Sci, Dept Cellular & Mol Med, Copenhagen, Denmark.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-62703-552-1; 978-1-62703-553-8
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1050
BP V
EP V
D2 10.1007/978-1-62703-553-8
PG 1
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BJM59
UT WOS:000329161900001
ER
PT S
AU Englund, EA
Zhang, N
Appella, DH
AF Englund, Ethan A.
Zhang, Ning
Appella, Daniel H.
BE Nielsen, PE
Appella, DH
TI Cyclopentane Peptide Nucleic Acids
SO PEPTIDE NUCLEIC ACIDS: METHODS AND PROTOCOLS, 2ND EDITION
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE PNA; Cyclopentane; Nucleic acid
ID BACKBONE MODIFICATION; DNA DUPLEXES
AB Incorporating a cyclopentane ring into the two-carbon unit of a peptide nucleic acid backbone increases its binding affinity to complementary nucleic acid sequences. This approach is a general method to improve binding and can be applied at either purine or pyrimidine bases.
C1 [Englund, Ethan A.; Zhang, Ning; Appella, Daniel H.] NIDDK, Sect Synthet Bioact Mol, Bioorgan Chem Lab, NIH,DHHS, Bethesda, MD 20892 USA.
RP Englund, EA (reprint author), NIDDK, Sect Synthet Bioact Mol, Bioorgan Chem Lab, NIH,DHHS, Bethesda, MD 20892 USA.
NR 7
TC 1
Z9 1
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-62703-552-1; 978-1-62703-553-8
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1050
BP 13
EP 18
DI 10.1007/978-1-62703-553-8_2
D2 10.1007/978-1-62703-553-8
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA BJM59
UT WOS:000329161900003
PM 24297347
ER
PT J
AU Cotugna, N
Fanelli-Kuczmarski, M
Clymer, J
Hotchkiss, L
Zonderman, AB
Evans, MK
AF Cotugna, Nancy
Fanelli-Kuczmarski, Marie
Clymer, Julie
Hotchkiss, Lawrence
Zonderman, Alan B.
Evans, Michele K.
TI Sodium intake of special populations in the Healthy Aging in
Neighborhoods of Diversity Across the Life Span (HANDLS) study (vol 57,
pg 334, 2013)
SO PREVENTIVE MEDICINE
LA English
DT Correction
C1 [Cotugna, Nancy; Fanelli-Kuczmarski, Marie; Hotchkiss, Lawrence] Univ Delaware, Dept Behav Hlth &Nutr, Newark, DE 19701 USA.
[Clymer, Julie] Wilmington VA Med Hosp, Wilmington, DE USA.
[Zonderman, Alan B.] NIA, Res Resources Branch, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Evans, Michele K.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
RP Cotugna, N (reprint author), Univ Delaware, Dept Behav Hlth &Nutr, 26 N Coll Ave, Newark, DE 19701 USA.
EM ncotugna@udel.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD JAN
PY 2014
VL 58
BP 87
EP 87
DI 10.1016/j.ypmed.2013.10.016
PG 1
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 295AL
UT WOS:000330088900016
ER
PT J
AU Pichu, S
Ribeiro, JMC
Mather, TN
Francischetti, IMB
AF Pichu, Sivakamasundari
Ribeiro, Jose M. C.
Mather, Thomas N.
Francischetti, Ivo M. B.
TI Purification of a serine protease and evidence for a protein C activator
from the saliva of the tick, Ixodes scapularis
SO TOXICON
LA English
DT Article
DE Serine protease; Saliva; Ixodes scapularis; Protease activated receptors
(PAR); Activated protein C (APC)
ID HAEMAPHYSALIS-LONGICORNIS; EXPRESSION PROFILE; GLAND; INFLAMMATION;
INHIBITOR; TRYPSIN; MECHANISMS; DISEASES; SIALOME; CLONING
AB The saliva of ticks is critical to their survival as parasites and hematophagous animals. In this study, we have purified an enzyme with trypsin-like activity from the saliva of the tick vector of Lyme Disease, Ixodes scapularis. This enzyme, named as IXOSP (I. scapularis salivary serine protease), is a 29.9 kDa molecule with N-terminus FPxMVxLRIKxR. A BLAST search identified IXOSP as a secreted serine protease (AAY66740) with a conserved catalytic triad His, Asp, and Set. In vitro studies demonstrated that IXOSP cleaves chromogenic substrates with arginine in the P-1 position, by a mechanism inhibited by PMSF or aprotinin. Gene expression studies revealed that IXOSP is expressed at different tick developmental stages, including eggs, and unfed or fed adult tick salivary glands, but not in nymphs or in the midgut While the physiological substrate for IXOSP remains to be identified, we demonstrated that I. scapularis saliva activate protein C (PC) resulting in the production of activated PC, a potent anticoagulant that also regulates a myriad of inflammatory responses through protease activated receptors. In contrast, the salivary glands of Anopheles gambiae, Anopheles stephensi, Anopheles albimanus, Aedes aegypti, Lutzomyia longipalpis, and Phlebotomus ariasi did not activate protein C. These discoveries are discussed in the context of blood coagulation, inflammation and vector-host interactions. Published by Elsevier Ltd.
C1 [Pichu, Sivakamasundari; Mather, Thomas N.] Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA.
[Ribeiro, Jose M. C.; Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Pichu, S (reprint author), Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA.
EM au_sudha@yahoo.com; ifrancischetti@niaid.nih.gov
RI Ribeiro, Jose/J-7011-2015;
OI Ribeiro, Jose/0000-0002-9107-0818
FU National Institute of Health [AI 37230, 1U19 AI 082642, P20 RR16457];
Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; URI Proteomics Core facility; [2006-34438-17306]
FX This work was supported by National Institute of Health Grant AI 37230
(TNM) and 1U19 AI 082642 (TNM), a subcontract to USDA Special Grant
2006-34438-17306 (TNM), and by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. Experiments were
supported by the URI Proteomics Core facility, made available by the
RI-BRIN and RI-INBRE (NIH award P20 RR16457). We are grateful to Nathan
Miller for helpful technical discussions. We also thank NIAID intramural
editor Brenda Rae Marshall for assistance. Because IMBF and JMCR are
government employee and this is a government work, the work is in the
public domain of the United States. Notwithstanding any other
agreements, the NIH reserves the right to provide the work to
PubMedCentral for display and use by the public, and PubMedCentral may
tag or modify the work consistent with its customary practices.
NR 39
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U1 2
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0041-0101
J9 TOXICON
JI Toxicon
PD JAN
PY 2014
VL 77
BP 32
EP 39
DI 10.1016/j.toxicon.2013.10.025
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 293CK
UT WOS:000329948800005
PM 24184517
ER
PT J
AU Love, PE
Warzecha, C
Li, LQ
AF Love, Paul E.
Warzecha, Claude
Li, LiQi
TI Ldb1 complexes: the new master regulators of erythroid gene
transcription
SO TRENDS IN GENETICS
LA English
DT Review
DE erythropoiesis; Gata1; Tal1; Klf1; Ldb1 complexes; transcriptional
regulation; ChIP-Seq
ID KRUPPEL-LIKE FACTOR; BETA-GLOBIN LOCUS; HEMATOPOIETIC STEM-CELLS;
GENOME-WIDE ANALYSIS; FACTOR EKLF GENE; FACTOR GATA-1; CHROMATIN
OCCUPANCY; LEUKEMIA GENE; PROTEIN LMO2; MICE LACKING
AB Elucidation of the genetic pathways that control red blood cell development has been a central goal of erythropoiesis research over the past decade. Notably, data from several recent studies have provided new insights into the regulation of erythroid gene transcription. Transcription profiling demonstrates that erythropoiesis is mainly controlled by a small group of lineage-restricted transcription factors [Gata binding protein 1 (Gata1), T cell acute lymphocytic leukemia 1 protein (Tal1), and Erythroid Kruppel-like factor (EKLF; henceforth referred to as Klf1)]. Binding-site mapping using ChIP-Seq indicates that most DNA-bound Gata1 and Tal1 proteins are contained within higher order complexes (Ldb1 complexes) that include the nuclear adapters Ldb1 and Lmo2. Ldb1 complexes regulate Klf1, and Ldb1 complex-binding sites frequently colocalize with Klf1 at erythroid genes and cis-regulatory elements, indicating strong functional synergy between Gata1, Tal1, and Klf1. Together with new data demonstrating that Ldb1 can mediate long-range promoter-enhancer interactions, these findings provide a foundation for the first comprehensive models of the global regulation of erythroid gene transcription.
C1 [Love, Paul E.; Warzecha, Claude; Li, LiQi] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Love, PE (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA.
EM lovep@mail.nih.gov
FU Intramural Research Programs of Eunice Kennedy Shriver NICBD
[1ZIAHD001803-19]
FX This work was supported by the Intramural Research Programs of Eunice
Kennedy Shriver NICBD [Project number1ZIAHD001803-19 (to P.E.L.)]. The
authors thank Karl Pfeifer for critical review of the manuscript.
NR 75
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U1 1
U2 15
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD JAN
PY 2014
VL 30
IS 1
BP 1
EP 9
DI 10.1016/j.tig.2013.10.001
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 293ZW
UT WOS:000330013200001
PM 24290192
ER
PT J
AU Niciu, MJ
Henter, ID
Sanacora, G
Zarate, CA
AF Niciu, Mark J.
Henter, Ioline D.
Sanacora, Gerard
Zarate, Carlos A., Jr.
TI Glial abnormalities in substance use disorders and depression: Does
shared glutamatergic dysfunction contribute to comorbidity?
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Glia; depression; glutamate; alcohol use disorders; drug use disorders
ID D-ASPARTATE ANTAGONIST; FIBRILLARY ACIDIC PROTEIN; DORSOLATERAL
PREFRONTAL CORTEX; NECROSIS-FACTOR-ALPHA; LATE-LIFE DEPRESSION;
CONDITIONED PLACE PREFERENCE; ANTERIOR CINGULATE CORTEX; INDUCED
SICKNESS BEHAVIOR; ABSTINENT COCAINE USERS; CLOCK GENE PER2
AB Objectives. Preclinical and clinical research in neuropsychiatric disorders, particularly mood and substance use disorders, have historically focused on neurons; however, glial cells - astrocytes, microglia, and oligodendrocytes - also play key roles in these disorders. Methods. Peer-reviewed PubMed/Medline articles published through December 2012 were identified using the following keyword combinations: glia, astrocytes, oligodendrocytes/glia, microglia, substance use, substance abuse, substance dependence, alcohol, opiate, opioid, cocaine, psychostimulants, stimulants, and glutamate. Results. Depressive and substance use disorders are highly comorbid, suggesting a common or overlapping aetiology and pathophysiology. Reduced astrocyte cell number occurs in both disorders. Altered glutamate neurotransmission and metabolism - specifically changes in the levels/activity of transporters, receptors, and synaptic proteins potentially related to synaptic physiology - appear to be salient features of both disorders. Glial cell pathology may also underlie the pathophysiology of both disorders via impaired astrocytic production of neurotrophic factors. Microglial/neuroinflammatory pathology is also evident in both depressive and substance use disorders. Finally, oligodendrocyte impairment decreases myelination and impairs expression of myelin-related genes in both substance use and depressive disorders. Conclusions. Glial-mediated glutamatergic dysfunction is a common neuropathological pathway in both substance use and depression. Therefore, glutamatergic neuromodulation is a rational drug target in this comorbidity.
C1 [Niciu, Mark J.; Sanacora, Gerard] Yale Univ, Dept Psychiat, CMHC, CNRU, New Haven, CT 06520 USA.
[Niciu, Mark J.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, Bethesda, MD 20814 USA.
[Henter, Ioline D.] NIMH, Mol Imaging Branch, Bethesda, MD 20814 USA.
RP Niciu, MJ (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Room 7-5545, Bethesda, MD 20814 USA.
EM mark.niciu@nih.gov
RI Niciu, Mark/J-1766-2014
OI Niciu, Mark/0000-0002-5612-3021
FU AstraZeneca; Avanier Pharmaceuticals; Bristol-Myers Squibb; Evotec; Eli
Lilly Co.; Hoffman La-Roche; Naurex; Novartis; Novum Pharmaceuticals;
Eli Lilly; Merck Co.; Severier; Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH); Department of Veterans Affairs; VA National Center for
PTSD; National Alliance for Research on Schizophrenia and Depression
(NARSAD); NIMH [R01 MH071676-05, R01 MH081211-3, T32 MH19961, R25
MH071584]; State of Connecticut Department of Mental Health and
Addiction Services; NARSAD Independent Investigator Award; Brain and
Behavior Foundation Bipolar Research Award
FX Dr Niciu and Ms Henter have no potential conflicts of interest to
disclose, financial or otherwise. Dr Sanacora has received consulting
fees from AstraZeneca, Avanier Pharmaceuticals, Bristol-Myers Squibb,
Evotec, Eli Lilly & Co., Hoffman La-Roche, Naurex, Novartis and Novum
Pharmaceuticals over the last 24 months. He has also received additional
grant support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Hoffman
La-Roche, Merck & Co., Naurex, and Severier over the last 24 months. In
addition, he is a co-inventor on a filed patent application by Yale
University (PCTWO06108055A1) concerning the use of glutamate-modulating
drugs as antidepressants and anxiolytics. Dr Zarate is listed as a
co-inventor on a patent application for the use of ketamine and its
metabolites in major depression. Dr Zarate has assigned his rights in
the patent to the US Government but will share a percentage of any
royalties that may be received.; This work was supported in part by the
Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); by the Department of
Veterans Affairs, via its funding of the VA National Center for PTSD
(GS); by the National Alliance for Research on Schizophrenia and
Depression (NARSAD) (GS); by NIMH grants R01 MH071676-05 and R01
MH081211-3 (GS); by the State of Connecticut Department of Mental Health
and Addiction Services (through its support of clinical research
services at the Connecticut Mental Health Center and Clinical
Neuroscience Research Unit) (GS); by salary support from NIMH T32
MH19961 and R25 MH071584 (MJN); and by a NARSAD Independent Investigator
Award and Brain and Behavior Foundation Bipolar Research Award (CAZ).
NR 187
TC 6
Z9 6
U1 1
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1562-2975
EI 1814-1412
J9 WORLD J BIOL PSYCHIA
JI World J. Biol. Psychiatry
PD JAN
PY 2014
VL 15
IS 1
BP 2
EP 16
DI 10.3109/15622975.2013.829585
PG 15
WC Psychiatry
SC Psychiatry
GA 291KT
UT WOS:000329828300002
PM 24024876
ER
PT J
AU Feero, WG
Guttmacher, AE
AF Feero, William Gregory
Guttmacher, Alan E.
TI Genomics, Personalized Medicine, and Pediatrics
SO ACADEMIC PEDIATRICS
LA English
DT Article
DE genetics; genomics; genotyping; pediatrics; personalized medicine;
sequencing
ID HUMAN MICROBIOME; GENOMEWIDE ASSOCIATION; WIDE ASSOCIATION; LARGE-SCALE;
DISEASE; OUTBREAK; CANCER; OBESITY; HEALTH; METHYLATION
AB Genomic discoveries are advancing biomedicine at an ever-increasing pace. Pediatrics is near the epicenter of these discoveries, which are revising our understanding of the genome and its function. Since the completion of the Human Genome Project in 2003, dramatic reductions in the cost of genotyping, and more recently sequencing, have permitted the study of the genomes of a great number of species as well as humans. These studies have led to insights on gene regulation and the complex interplay of factors responsible for normal development and biology. Study of single-gene disorders has greatly benefited from the genomics revolution and tests are now available for well over 2000 Mendelian conditions; availability of these tests are changing screening and diagnosis paradigms for rare conditions. Genomics is also yielding an increased understanding of common conditions such as diabetes, obesity, asthma, cancers, and mental health conditions. Personalized medicine, an approach to care in which an individual's genomic information is used to help tailor interventions to maximize health outcomes, is rapidly becoming a reality for a variety of conditions. Though challenges remain in translating new genomic insights into improved patient health, today's pediatricians and their patients will increasingly benefit from this watershed moment in the biological sciences.
C1 [Feero, William Gregory] MaineDartmouth Family Med Residency Program, Augusta, ME USA.
[Guttmacher, Alan E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Feero, WG (reprint author), 4 Sheridan Dr,Suite 2, Fairfield, ME 04937 USA.
EM wfeero@mainegeneral.org
FU Intramural NIH HHS [Z99 CA999999]
NR 58
TC 9
Z9 10
U1 5
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1876-2859
EI 1876-2867
J9 ACAD PEDIATR
JI Acad. Pediatr.
PD JAN-FEB
PY 2014
VL 14
IS 1
BP 14
EP 22
PG 9
WC Pediatrics
SC Pediatrics
GA 287SS
UT WOS:000329563100005
PM 24369865
ER
PT J
AU Brimacombe, KR
Walsh, MJ
Liu, L
Vasquez-Valdivieso, MG
Morgan, HP
McNae, I
Fothergill-Gilmore, LA
Michels, PAM
Auld, DS
Simeonov, A
Walkinshaw, MD
Shen, M
Boxer, MB
AF Brimacombe, Kyle R.
Walsh, Martin J.
Liu, Li
Vasquez-Valdivieso, Montserrat G.
Morgan, Hugh P.
McNae, Iain
Fothergill-Gilmore, Linda A.
Michels, Paul A. M.
Auld, Douglas S.
Simeonov, Anton
Walkinshaw, Malcolm D.
Shen, Min
Boxer, Matthew B.
TI Identification of ML251, a Potent Inhibitor of T. brucei and T. cruzi
Phosphofructokinase
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Trypanosoma brucei; Trypanosoma cruzi; phosphofructokinase; inhibitors;
glycolysis; high-throughput screening
ID TRYPANOSOMA-BRUCEI; DRUG DISCOVERY; GLYCOLYSIS; PARASITE; DESIGN; TARGET
AB Human African Trypanosomiasis (HAT) is a severe, often fatal disease caused by the parasitic protist Trypanosoma brucei. The glycolytic pathway has been identified as the sole mechanism for ATP generation in the infective stage of these organisms, and several glycolytic enzymes, phosphofructokinase (PFK) in particular, have shown promise as potential drug targets. Herein, we describe the discovery of ML251, a novel nanomolar inhibitor of T. brucei PFK, and the structure-activity relationships within the series.
C1 [Brimacombe, Kyle R.; Walsh, Martin J.; Liu, Li; Auld, Douglas S.; Simeonov, Anton; Shen, Min; Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Vasquez-Valdivieso, Montserrat G.; Morgan, Hugh P.; McNae, Iain; Fothergill-Gilmore, Linda A.; Walkinshaw, Malcolm D.] Univ Edinburgh, Sch Biol Sci, Ctr Translat & Chem Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
[Michels, Paul A. M.] Catholic Univ Louvain, Trop Dis Res Unit, de Duve Inst, B-1200 Brussels, Belgium.
[Michels, Paul A. M.] Catholic Univ Louvain, Biochem Lab, B-1200 Brussels, Belgium.
RP Boxer, MB (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM boxerm@mail.nih.gov
RI Michels, Paul/A-5637-2009;
OI walkinshaw, malcolm/0000-0001-5955-9325
FU Molecular Libraries Initiative of the NIH Roadmap for Medical Research
[R03MH092153-01, U54MH084681]
FX This research was supported in part by Award No. R03MH092153-01 from the
Molecular Libraries Initiative of the NIH Roadmap for Medical Research
(grant U54MH084681).
NR 16
TC 6
Z9 7
U1 2
U2 23
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD JAN
PY 2014
VL 5
IS 1
BP 12
EP 17
DI 10.1021/ml400259d
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 289JI
UT WOS:000329677900005
PM 24900769
ER
PT J
AU Bhambhani, V
Muenke, M
AF Bhambhani, Vikas
Muenke, Maximilian
TI Noonan Syndrome
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Article
ID MANAGEMENT; DIAGNOSIS; FEATURES; PTPN11
AB Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome specific growth charts and treatment guidelines are available. Copyright (C) 2014 American Academy of Family Physicians.
C1 [Bhambhani, Vikas] NHGRI, NIH, Bethesda, MD 20892 USA.
[Bhambhani, Vikas; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
FU Intramural NIH HHS [Z99 HG999999]
NR 17
TC 6
Z9 6
U1 1
U2 5
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
EI 1532-0650
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD JAN 1
PY 2014
VL 89
IS 1
BP 37
EP 43
PG 7
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 289KV
UT WOS:000329682300007
PM 24444506
ER
PT J
AU Coleman, HG
Kitahara, CM
Murray, LJ
Dodd, KW
Black, A
Stolzenberg-Solomon, RZ
Cantwell, MM
AF Coleman, Helen G.
Kitahara, Cari M.
Murray, Liam J.
Dodd, Kevin W.
Black, Amanda
Stolzenberg-Solomon, Rachael Z.
Cantwell, Marie M.
TI Dietary Carbohydrate Intake, Glycemic Index, and Glycemic Load and
Endometrial Cancer Risk: A Prospective Cohort Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE carbohydrate; dietary fiber; endometrial cancer; glycemic index;
glycemic load
ID FOOD FREQUENCY QUESTIONNAIRES; UNITED-STATES; ENERGY-INTAKE; NUTRITIONAL
FACTORS; PHYSICAL-ACTIVITY; SCREENING TRIAL; METAANALYSIS; FIBER;
ASSOCIATION; INSTITUTE
AB Endometrial cancer risk has been directly associated with glycemic load. However, few studies have investigated this link, and the etiological role of specific dietary carbohydrate components remains unclear. Our aim was to investigate associations of carbohydrate intake, glycemic index, and glycemic load with endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Recruitment took place in 19932001. Over a median of 9.0 years of follow-up through 2009, 386 women developed endometrial cancer among 36,115 considered in the analysis. Dietary intakes were assessed using a 124-item diet history questionnaire. Cox proportional hazards models were applied to calculate hazard ratios and 95 confidence intervals. Significant inverse associations were detected between endometrial cancer risk and total available carbohydrate intake (hazard ratio (HR) 0.66, 95 confidence interval (CI): 0.49, 0.90), total sugars intake (HR 0.71, 95 CI: 0.52, 0.96), and glycemic load (HR 0.63, 95 CI: 0.46, 0.84) when women in the highest quartile of intake were compared with those in the lowest. These inverse associations were strongest among overweight and obese women. No associations with endometrial cancer risk were observed for glycemic index or dietary fiber. Our findings contrast with previous evidence and suggest that high carbohydrate intakes and glycemic loads are protective against endometrial cancer development. Further clarification of these associations is warranted.
C1 [Coleman, Helen G.; Murray, Liam J.; Cantwell, Marie M.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Belfast BT12 6BJ, Antrim, North Ireland.
[Kitahara, Cari M.; Black, Amanda; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Dodd, Kevin W.] NCI, Canc Prevent Div, Rockville, MD USA.
RP Coleman, HG (reprint author), Queens Univ Belfast, Royal Victoria Hosp, Ctr Publ Hlth, ICS B Bldg,Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM h.coleman@qub.ac.uk
RI Kitahara, Cari/R-8267-2016;
OI Coleman, Helen/0000-0003-4872-7877
FU Medical Research Council [MR/K023241/1]
NR 46
TC 5
Z9 6
U1 0
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 1
PY 2014
VL 179
IS 1
BP 75
EP 84
DI 10.1093/aje/kwt222
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 280WI
UT WOS:000329061100011
PM 24091889
ER
PT J
AU Wirdefeldt, K
Weibull, CE
Chen, HL
Kamel, F
Lundholm, C
Fang, F
Ye, WM
AF Wirdefeldt, Karin
Weibull, Caroline E.
Chen, Honglei
Kamel, Freya
Lundholm, Cecilia
Fang, Fang
Ye, Weimin
TI Parkinson's Disease and Cancer: A Register-based Family Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cancer; cohort studies; hazard ratio; Parkinson's disease; siblings
ID MALIGNANT-MELANOMA; RISK
AB We wanted to compare cancer incidence rates between Parkinson's disease (PD) patients and persons without PD, as well as between siblings of these groups. We conducted a family-based matched cohort study based on nationwide Swedish health registries and the Swedish Multi-Generation Register. We assessed risk of incident cancer in PD patients (n = 11,786) during 1964-2009 versus a matched cohort of PD-free individuals (n = 58,930) and in siblings of PD patients (n = 16,841) versus siblings of PD-free individuals (n = 84,205). Hazard ratios with 95% confidence intervals were estimated using Cox proportional hazards regression. Cancer occurrence was slightly higher in PD patients than in PD-free individuals (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 1.00, 1.10), largely because of cancers arising within 1 year before or after the index date for PD, but risk of smoking-related cancers was lower (HR = 0.87, 95% CI: 0.79, 0.96). PD patients had a higher risk of melanoma both up to 1 year before the PD index date (HR = 1.53, 95% CI: 1.23, 1.91) and from 1 year after the index date onward (HR = 1.46, 95% CI: 1.01, 2.10). In the sibling comparison, cancer occurrence was largely similar. These results indicate that melanoma risk is higher among PD patients and that mechanisms other than familial ones explain the association.
C1 [Wirdefeldt, Karin; Weibull, Caroline E.; Lundholm, Cecilia; Fang, Fang; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Wirdefeldt, Karin] Karolinska Inst, Dept Clin Neurosci, SE-17177 Stockholm, Sweden.
[Chen, Honglei; Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Wirdefeldt, K (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden.
EM karin.wirdefeldt@ki.se
OI Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615;
Lundholm, Cecilia/0000-0002-6546-3650; Chen, Honglei/0000-0003-3446-7779
FU Swedish Research Council (SIMSAM) [80748301]; Swedish Parkinson
Foundation; Swedish Medical Society; Swedish Society for Medical
Research; Swedish Brain Foundation; Intramural Research Program of the
US National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES-101986]
FX This work was supported by grants from the Swedish Research Council
(SIMSAM grant 80748301), the Swedish Parkinson Foundation, the Swedish
Medical Society, the Swedish Society for Medical Research, and the
Swedish Brain Foundation. The study was also partially supported by the
Intramural Research Program of the US National Institutes of Health,
National Institute of Environmental Health Sciences (grant
Z01ES-101986).
NR 20
TC 18
Z9 18
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 1
PY 2014
VL 179
IS 1
BP 85
EP 94
DI 10.1093/aje/kwt232
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 280WI
UT WOS:000329061100012
PM 24142916
ER
PT J
AU Zablotska, LB
Little, MP
Cornett, RJ
AF Zablotska, Lydia B.
Little, Mark P.
Cornett, R. Jack
TI Potential Increased Risk of Ischemic Heart Disease Mortality With
Significant Dose Fractionation in the Canadian Fluoroscopy Cohort Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cardiovascular disease; dose fractionation; ionizing radiation; ischemic
heart disease; noncancer diseases; radiation dose-response relationship
ID ATOMIC-BOMB SURVIVORS; INDUCED CARDIOVASCULAR-DISEASE; CHILDHOOD-CANCER
SURVIVOR; RATE IONIZING-RADIATION; LONG-TERM SURVIVORS; BREAST-CANCER;
CIRCULATORY DISEASE; TUBERCULOSIS PATIENTS; LUNG-CANCER; EXPOSURE
AB Risks of noncancer causes of death, particularly cardiovascular disease, associated with exposures to high-dose ionizing radiation, are well known. Recent studies have reported excess risk in workers who are occupationally exposed to low doses at a low dose rate, but the risks of moderately fractionated exposures, such as occur during diagnostic radiation procedures, remain unclear. The Canadian Fluoroscopy Cohort Study includes 63,707 tuberculosis patients exposed to multiple fluoroscopic procedures in 19301952 and followed-up for death from noncancer causes in 19501987. We used a Poisson regression to estimate excess relative risk (ERR) per Gy of cumulative radiation dose to the lung (mean dose 0.79 Gy; range, 011.60). The risk of death from noncancer causes was significantly lower in these subjects compared with the Canadian general population (P 0.001). We estimated small, nonsignificant increases in the risk of death from noncancer causes with dose. We estimated an ERR/Gy of 0.176 (95 confidence interval: 0.011, 0.393) (n 5,818 deaths) for ischemic heart disease (IHD) after adjustment for dose fractionation. A significant (P 0.022) inverse dose fractionation effect in dose trends of IHD was observed, with the highest estimate of ERR/Gy for those with the fewest fluoroscopic procedures per year. Radiation-related risks of IHD decreased significantly with increasing time since first exposure and age at first exposure (both P 0.05). This is the largest study of patients exposed to moderately fractionated low-to-moderate doses of radiation, and it provides additional evidence of increased radiation-associated risks of death from IHD, in particular, significantly increased radiation risks from doses similar to those from diagnostic radiation procedures. The novel finding of a significant inverse dose-fractionation association in IHD mortality requires further investigation.
C1 [Zablotska, Lydia B.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Little, Mark P.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Cornett, R. Jack] Hlth Canada, Radiat Protect Bur, Ottawa, ON K1A 0L2, Canada.
RP Zablotska, LB (reprint author), 3333 Calif St,Suite 280, San Francisco, CA 94118 USA.
EM lydia.zablotska@ucsf.edu
OI Little, Mark/0000-0003-0980-7567
FU National Institutes of Health; National Cancer Institute [CA132918];
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics
FX L.B.Z. was supported by the National Institutes of Health, the National
Cancer Institute (grant CA132918). M. P. L. was supported by the
Intramural Research Program of the National Institutes of Health, the
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
NR 44
TC 6
Z9 9
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JAN 1
PY 2014
VL 179
IS 1
BP 120
EP 131
DI 10.1093/aje/kwt244
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 280WI
UT WOS:000329061100015
PM 24145888
ER
PT J
AU Rada, B
Boudreau, HE
Park, JJ
Leto, TL
AF Rada, Balazs
Boudreau, Howard E.
Park, Jonathan J.
Leto, Thomas L.
TI Histamine Stimulates Hydrogen Peroxide Production by Bronchial
Epithelial Cells via Histamine H1 Receptor and Dual Oxidase
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE Duox; NADPH oxidase; asthma; airway epithelium; oxidative stress
ID GROWTH-FACTOR RECEPTOR; ATP-MEDIATED ACTIVATION; NADPH OXIDASE;
PSEUDOMONAS-AERUGINOSA; BREATH CONDENSATE; MUCIN EXPRESSION; OXIDATIVE
STRESS; HOST-DEFENSE; KAPPA-B; ASTHMA
AB Oxidative stress has been implicated in the pathogenesis of bronchial asthma. Besides granulocytes, the airway epithelium can produce large amounts of reactive oxygen species and can contribute to asthma-related oxidative stress. Histamine is a major inflammatory mediator present in large quantities in asthmatic airways. Whether histamine triggers epithelium-derived oxidative stress is unknown. We therefore aimed at characterizing human airway epithelial H2O2 production stimulated by histamine. We found that air-liquid interface cultures of primary human bronchial epithelial cells (BECs) and an immortalized BEC model (Cdk4/hTERT HBEC) produce H2O2 in response to histamine. The main source of airway epithelial H2O2 is an NADPH dual oxidase, Duox1. Out of the four histamine receptors (H1R-H4R), H1R has the highest expression in BECs and mediates the H2O2-producing effects of histamine. IL-4 induces Duoxl gene and protein expression levels and enhances histamine-induced H2O2 production by epithelial cells. Using HEK-293 cells expressing Duox1 or Duox2 and endogenous H1R, histamine triggers an immediate intracellular calcium signal and H2O2 release. Overexpression of H1R further increases the oxidative output of Duox-expressing HEK-293 cells. Our observations show that BECs respond to histamine with Duox-mediated H2O2 production. These findings reveal a mechanism that could be an important contributor to oxidative stress characteristic of asthmatic airways, suggesting novel therapeutic targets for treating asthmatic airway disease.
C1 [Rada, Balazs] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA USA.
[Rada, Balazs; Boudreau, Howard E.; Park, Jonathan J.; Leto, Thomas L.] NIAID, Lab Host Defenses, NIH, Rockville, MD 20852 USA.
RP Leto, TL (reprint author), NIAID, Lab Host Defenses, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM tleto@niaid.nih.gov
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases
FX Supported by funds from the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases.
NR 53
TC 11
Z9 11
U1 0
U2 6
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JAN
PY 2014
VL 50
IS 1
BP 125
EP 134
DI 10.1165/rcmb.2013-0254OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 291IF
UT WOS:000329820900013
PM 23962049
ER
PT J
AU James, S
Takken, W
Collins, FH
Gottlieb, M
AF James, Stephanie
Takken, Willem
Collins, Frank H.
Gottlieb, Michael
TI Perspective Piece: Needs for Monitoring Mosquito Transmission of Malaria
in a Pre-Elimination World
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID ANOPHELES-GAMBIAE MOSQUITOS; VECTOR CONTROL; AGE; IDENTIFICATION;
EXPOSURE; AFRICA
AB As global efforts to eliminate malaria intensify, accurate information on vector populations and transmission dynamics is critical for directing control efforts, developing new control tools, and predicting the effects of these interventions under various conditions. Currently available sampling tools for mosquito population monitoring suffer from well-recognized limitations. As reported in this workshop summary, a recent gathering of medical entomologists, modelers, and malaria experts reviewed these issues and agreed that efforts are needed to improve methods to monitor key transmission parameters. Identified needs include standardized methods for sampling of both mosquito adults and larvae, improved tools for mosquito species identification and age-grading, and a better means for determining the entomological inoculation rate.
C1 [James, Stephanie; Gottlieb, Michael] Fdn Natl Inst Hlth, Div Sci, Bethesda, MD 20814 USA.
[Takken, Willem] Univ Wageningen & Res Ctr, Entomol Lab, Wageningen, Netherlands.
[Collins, Frank H.] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA.
RP James, S (reprint author), Fdn Natl Inst Hlth, Div Sci, 9650 Rockville Pike, Bethesda, MD 20814 USA.
EM sjames@fnih.org; willem.takken@wur.nl; frank@nd.edu; mgottlieb@fnih.org
FU Foundation for the National Institutes of Health through the
Vector-Based Control of Transmission: Discovery Research Program of the
Grand Challenges in Global Health Initiative
FX Support was provided by the Foundation for the National Institutes of
Health through the Vector-Based Control of Transmission: Discovery
Research Program of the Grand Challenges in Global Health Initiative.
NR 35
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PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JAN
PY 2014
VL 90
IS 1
BP 6
EP 10
DI 10.4269/ajtmh.13-0175
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 288BO
UT WOS:000329587200004
PM 24277786
ER
PT J
AU Mo, AX
Agosti, JM
Watson, JL
Hall, BF
Gordon, L
AF Mo, Annie X.
Agosti, Jan M.
Watson, Judd L.
Hall, B. Fenton
Gordon, Lance
TI Schistosomiasis Elimination Strategies and Potential Role of a Vaccine
in Achieving Global Health Goals
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
AB In March 2013, the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation co-sponsored a meeting entitled "Schistosomiasis Elimination Strategy and Potential Role of a Vaccine in Achieving Global Health Goals" to discuss the potential role of schistosomiasis vaccines and other tools in the context of schistosomiasis control and elimination strategies. It was concluded that although schistosomiasis elimination in some focal areas may be achievable through current mass drug administration programs, global control and elimination will face several significant scientific and operational challenges, and will require an integrated approach with other, additional interventions. These challenges include vector (snail) control; environmental modification; water, sanitation, and hygiene; and other future innovative tools such as vaccines. Defining a clear product development plan that reflects a vaccine strategy as complementary to the existing control programs to combat different forms of schistosomiasis will be important to develop a vaccine effectively.
C1 [Mo, Annie X.; Hall, B. Fenton] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
[Agosti, Jan M.; Gordon, Lance] Bill & Melinda Gates Fdn, Seattle, WA USA.
[Watson, Judd L.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Watson, Judd L.] Univ Washington, Dept Med, Seattle, WA USA.
[Watson, Judd L.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
RP Mo, AX (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM annie.mo@nih.gov; jan.agosti@gatesfoundation.org; walson@uw.edu;
lhall@niaid.nih.gov; lance.gordon@gatesfoundation.org
NR 0
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U2 12
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JAN
PY 2014
VL 90
IS 1
BP 54
EP 60
DI 10.4269/ajtmh.13-0467
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 288BO
UT WOS:000329587200011
PM 24402703
ER
PT J
AU Treger, RS
Otchere, J
Keil, MF
Quagraine, JE
Rai, G
Mott, BT
Humphries, DL
Wilson, M
Cappello, M
Vermeire, JJ
AF Treger, Rebecca S.
Otchere, Joseph
Keil, Martin F.
Quagraine, Josephine E.
Rai, Ganesha
Mott, Bryan T.
Humphries, Debbie L.
Wilson, Michael
Cappello, Michael
Vermeire, Jon J.
TI Short Report: In vitro Screening of Compounds against Laboratory and
Field Isolates of Human Hookworm Reveals Quantitative Differences in
Anthelmintic Susceptibility
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID EGG-HATCH ASSAY; NECATOR-AMERICANUS; ANCYLOSTOMA-CEYLANICUM; VETERINARY
IMPORTANCE; HELMINTH INFECTIONS; DRUG-SENSITIVITY; VIVO EFFICACY;
RESISTANCE; IVERMECTIN; NEMATODES
AB A panel of 80 compounds was screened for anthelmintic activity against a laboratory strain of Ancylostoma ceylanicum and field isolates of hookworm obtained from school children in the Kintampo North District of the Brong Ahafo Region of Ghana. Although the laboratory strain of A. ceylanicum was more susceptible to the compounds tested than the field isolates of hookworm, a twofold increase in compound concentration resulted in comparable egg hatch percent inhibition for select compounds. These data provide evidence that the efficacy of anthelmintic compounds may be species-dependent and that field and laboratory strains of hookworm differ in their sensitivities to the anthelmintics tested. These data also suggest that both compound concentration and hookworm species must be considered when screening to identify novel anthelmintic compounds.
C1 [Treger, Rebecca S.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Treger, Rebecca S.] Yale Univ, Sch Med, Program Int Child Hlth, New Haven, CT USA.
[Otchere, Joseph; Quagraine, Josephine E.; Wilson, Michael] Univ Ghana, Noguchi Mem Inst Med Res, Legon, Ghana.
NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Keil, Martin F.; Humphries, Debbie L.] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA.
[Rai, Ganesha; Mott, Bryan T.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Cappello, Michael; Vermeire, Jon J.] Yale Univ, Yale Child Hlth Res Ctr, New Haven, CT USA.
RP Vermeire, JJ (reprint author), Univ Calif San Francisco, Dept Pathol, QB3 Room 501e,Box 2550,1700 4th St, San Francisco, CA 94143 USA.
EM rebecca.treger@yale.edu; jotchere@noguchi.mimcom.org;
martin.keil@yale.edu; jquagraine@noguchi.mimcom.org;
bantukallug@mail.nih.gov; bryan.mott@nih.gov; debbie.humphries@yale.edu;
mwilson@noguchi.mimcom.org; michael.cappello@yale.edu;
jon.vermeire@yale.edu
FU National Institutes of Health Chemical Genomics Center
[HHSN268201000217P]; National Institutes of Health [K22 A08476]; Noguchi
Memorial Institute for Medical Research; Yale-Ghana Partnership in
Global Health
FX This work was supported by National Institutes of Health Chemical
Genomics Center Contract HHSN268201000217P (to M.C. and J.J.V.),
National Institutes of Health Career Development Award K22 A08476 (to
J.J.V.), the Noguchi Memorial Institute for Medical Research, and the
Yale-Ghana Partnership in Global Health.
NR 40
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U2 3
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JAN
PY 2014
VL 90
IS 1
BP 71
EP 74
DI 10.4269/ajtmh.12-0547
PG 4
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 288BO
UT WOS:000329587200013
PM 24297811
ER
PT J
AU Platts-Mills, JA
Gratz, J
Mduma, E
Svensen, E
Amour, C
Liu, J
Maro, A
Saidi, Q
Swai, N
Kumburu, H
McCormick, BJJ
Kibiki, G
Houpt, ER
AF Platts-Mills, James A.
Gratz, Jean
Mduma, Esto
Svensen, Erling
Amour, Caroline
Liu, Jie
Maro, Athanasia
Saidi, Queen
Swai, Ndealilia
Kumburu, Happiness
McCormick, Benjamin J. J.
Kibiki, Gibson
Houpt, Eric R.
TI Association Between Stool Enteropathogen Quantity and Disease in
Tanzanian Children Using TaqMan Array Cards: A Nested Case-Control Study
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID REAL-TIME PCR; INFECTIOUS INTESTINAL DISEASE; POLYMERASE-CHAIN-REACTION;
GROUP-A ROTAVIRUS; DEVELOPING-COUNTRIES; ENTERIC PATHOGENS; DIARRHEAL
DISEASE; FECAL SAMPLES; BANGLADESH; CRYPTOSPORIDIUM
AB Etiologic studies of diarrhea are limited by uneven diagnostic methods and frequent asymptomatic detection of enteropathogens. Polymerase chain reaction-based stool, pathogen quantification may help distinguish clinically significant infections. We performed a nested case-control study of diarrhea in infants from a community-based birth cohort in Tanzania. We tested 71 diarrheal samples and pre-diarrheal matched controls with a laboratory-developed TaqMan Array Card for 19 enteropathogens. With qualitative detection, no pathogens were significantly associated with diarrhea. When pathogen quantity was considered, rotavirus (odds ratio [OR] = 2.70 per log(10) increase, P < 0.001), astrovirus (OR = 1.49, P = 0.01), and Shigella/enteroinvasive Escherichia coli (OR = 1.47, P = 0.04) were associated with diarrhea. Enterotoxigenic E. coli (0.15 SD decline in length-for-age z score after 3 months per log(10) increase, P < 0.001) and Campylobacter jejuni/C. coli (0.11 SD decline, P = 0.003) in pre-diarrheal stools were associated with poor linear growth. Quantitative analysis can help refine the association between enteropathogens and disease in endemic settings.
C1 [Platts-Mills, James A.; Gratz, Jean; Liu, Jie; Houpt, Eric R.] Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA.
[Mduma, Esto; Svensen, Erling; Amour, Caroline] Haydom Lutheran Hosp, Haydom, Tanzania.
[Maro, Athanasia; Saidi, Queen; Swai, Ndealilia; Kumburu, Happiness; Kibiki, Gibson] Kilimanjaro Clin Res Inst, Moshi, Tanzania.
[McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Houpt, ER (reprint author), Univ Virginia, Dept Med, Div Infect Dis & Int Hlth, Mr4,2144, Charlottesville, VA 22908 USA.
EM jp5t@virginia.edu; jean.gratz@gmail.com; estomih.mduma@haydom.co.tz;
erling.svensen@cih.uib.no; lyneamour@gmail.com; jl5yj@virginia.edu;
athanasia.maro@gmail.com; queensaidi@gmail.com; lilia2005tz@yahoo.co.uk;
hk9s@virginia.edu; ben.mccormick@gmail.com; g.kibiki@kcri.ac.tz;
erh6k@virginia.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [U01 AI075396]; Bill & Melinda Gates Foundation
Global Health [OPP1019093]
FX This work was supported by National Institute of Allergy and Infectious
Diseases, National Institutes of Health Grant U01 AI075396 and Bill &
Melinda Gates Foundation Global Health Grant OPP1019093 (to E.R.H.).
NR 28
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U2 12
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JAN
PY 2014
VL 90
IS 1
BP 133
EP 138
DI 10.4269/ajtmh.13-0439
PG 6
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 288BO
UT WOS:000329587200023
PM 24189366
ER
PT J
AU Carothers, CL
Heimburger, DC
Schlachter, S
Gardner, P
Primack, A
Warner, TL
Vermund, SH
AF Carothers, Catherine L.
Heimburger, Douglas C.
Schlachter, Sarah
Gardner, Pierce
Primack, Aron
Warner, Tokesha L.
Vermund, Sten H.
TI Review Article: Training Programs Within Global Networks: Lessons
Learned in the Fogarty International Clinical Research Scholars and
Fellows Program
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID MEDICAL-STUDENTS; HEALTH; ELECTIVES; PARTNERSHIPS; INSTITUTIONS;
WORKFORCE
AB The Fogarty International Clinical Research Scholars and Fellows Support Center at Vanderbilt describes administrative lessons learned from the management of 436 scholars (American students or host country junior trainees) and 122 post-doctoral fellows (Americans or host country nationals). Trainees spent 10-11 months working on mentored research projects at 61 well-vetted sites in 27 low- or middle-income host countries (LMICs) with strong US partners. Economies of scale, strong centralized information exchange, and effective standardized operations linking US institutions with LMIC field sites were achieved in a program that minimized administrative overhead. Advantages and drawbacks of this approach are presented and discussed. Training of a new generation of global research leaders is greatly facilitated by an overseas mentored research experience that is administratively streamlined to optimize the use of resources for training, research, and capacity building.
C1 [Carothers, Catherine L.; Heimburger, Douglas C.; Vermund, Sten H.] Vanderbilt Univ, Inst Global Hlth, Nashville, TN 37203 USA.
Vanderbilt Univ, Fogarty Int Clin Res Scholars & Fellows Support C, Nashville, TN 37203 USA.
SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA.
NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Warner, Tokesha L.] Univ Georgia, Athens, GA 30602 USA.
[Schlachter, Sarah] Univ Kansas, Med Ctr, Frontiers, Fairway, KS USA.
[Gardner, Pierce] SUNY Stony Brook, Sch Med, Off Dean, Stony Brook, NY 11794 USA.
RP Carothers, CL (reprint author), Vanderbilt Univ, Inst Global Hlth, 2525 West End Ave,Suite 750, Nashville, TN 37203 USA.
EM catherine.lem@vanderbilt.edu; douglas.heimburger@vanderbilt.edu;
sschlachter@kumc.edu; pgardner@stonybrookmedicine.edu; aprimack@rcn.com;
gsmart@uga.edu; sten.vermund@vanderbilt.edu
FU NIH Office of the Director; Fogarty International Center; Office of AIDS
Research; National Cancer Institute; National Eye Institute; National
Heart, Blood, and Lung Institute; National Institute of Dental and
Craniofacial Research; National Institute on Drug Abuse; National
Institute of Mental Health; National Institute of Allergy and Infectious
Diseases Health through Fogarty International Clinical Research Fellows
Program at Vanderbilt-Association of American Medical Colleges [R24
TW007988]; American Recovery and Reinvestment Act (ARRA) funds
FX We thank Drs. Roger Glass, Kenneth Bridbord, and Myat Htoo Razak, Ms.
Yolanda Thomas, and the staff of the Fogarty International Center for
their support; the FICRS-F site principal investigators and field
mentors; and participating National Institutes of Health (NIH) institute
and center directors and staff. This work was supported by the NIH
Office of the Director, Fogarty International Center, Office of AIDS
Research, National Cancer Institute, National Eye Institute, National
Heart, Blood, and Lung Institute, National Institute of Dental and
Craniofacial Research, National Institute on Drug Abuse, National
Institute of Mental Health, and National Institute of Allergy and
Infectious Diseases Health through Fogarty International Clinical
Research Fellows Program R24 TW007988 at Vanderbilt-Association of
American Medical Colleges. Additional support in 2010 and 2011 was
received from American Recovery and Reinvestment Act (ARRA) funds
(http://recovery.nih.gov/).
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PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JAN
PY 2014
VL 90
IS 1
BP 173
EP 179
DI 10.4269/ajtmh.12-0512
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 288BO
UT WOS:000329587200031
PM 24297815
ER
PT J
AU Hartman, RL
Desrosiers, NA
Barnes, AJ
Yun, K
Scheidweiler, KB
Kolbrich-Spargo, EA
Gorelick, DA
Goodwin, RS
Huestis, MA
AF Hartman, Rebecca L.
Desrosiers, Nathalie A.
Barnes, Allan J.
Yun, Keming
Scheidweiler, Karl B.
Kolbrich-Spargo, Erin A.
Gorelick, David A.
Goodwin, Robert S.
Huestis, Marilyn A.
TI 3,4-Methylenedioxymethamphetamine (MDMA) and metabolites disposition in
blood and plasma following controlled oral administration
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE MDMA; Ecstasy; Pharmacokinetics; Metabolites; Blood; Plasma
ID WHOLE-BLOOD; FLUORESCENCE DETECTION; HUMAN PHARMACOLOGY;
MASS-SPECTROMETRY; ECSTASY; URINE; DRUG; MDA; HUMANS; HPLC
AB 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit phenethylamine ingested for entactogenic and euphoric effects. Although blood is more commonly submitted for forensic analysis, previous human MDMA pharmacokinetics research focused on plasma data; no direct blood-plasma comparisons were drawn. Blood and plasma specimens from 50 healthy adult volunteers (33 males, 17 females, 36 African-American) who ingested recreational 1.0 and 1.6 mg/kg MDMA doses were quantified for MDMA and metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxyamphetamine (MDA), and 4-hydroxy-3-methoxyamphetamine (HMA) by two-dimensional gas chromatography-mass spectrometry. Specimens were collected up to 3 h post-dose and evaluated for maximum concentration (C-max), first detection time (t(first)), time of C-max (t(max)), and 3-h area under the curve (AUC(0-3 h)); as well as blood metabolite ratios and blood/plasma ratios. Median blood MDMA and MDA C-max were significantly greater (p < 0.0005) than in plasma, but HMMA was significantly less (p < 0.0005). HMA was detected in few blood specimens, at low concentrations. Nonlinear pharmacokinetics were not observed for MDMA or MDA in this absorptive phase, but HMMA C-max and AUC(0-3 h) were similar for both doses despite the 1.6-fold dose difference. Blood MDA/MDMA and MDA/HMMA significantly increased (p < 0.0001) over the 3-h time course, and HMMA/MDMA significantly decreased (p < 0.0001). Blood MDMA C-max was significantly greater in females (p = 0.010) after the low dose only. Low-dose HMMA AUC(0-3 h) was significantly decreased in females' blood and plasma (p = 0.027) and in African-Americans' plasma (p = 0.035). These data provide valuable insight into MDMA blood-plasma relationships for forensic interpretation and evidence of sex-and race-based differential metabolism and risk profiles.
C1 [Hartman, Rebecca L.; Desrosiers, Nathalie A.; Barnes, Allan J.; Yun, Keming; Scheidweiler, Karl B.; Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Hartman, Rebecca L.; Desrosiers, Nathalie A.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Yun, Keming] Shanxi Med Univ, Sch Forens Med, Taiyuan 030001, Peoples R China.
[Kolbrich-Spargo, Erin A.] Southwestern Inst Forens Sci, Dallas, TX 75207 USA.
[Gorelick, David A.] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program,NIH, 251 Bayview Blvd,Suite 200 Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse, NIH
FX We thank the National Institute on Drug Abuse Intramural Research
Program and Johns Hopkins Bayview Medical Center Behavioral Pharmacology
Research Unit clinical staff. We further acknowledge the Graduate
Partnership Program, National Institutes of Health. This research was
funded by the Intramural Research Program, National Institute on Drug
Abuse, NIH.
NR 36
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PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JAN
PY 2014
VL 406
IS 2
BP 587
EP 599
DI 10.1007/s00216-013-7468-y
PG 13
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 288QK
UT WOS:000329626600022
PM 24232751
ER
PT J
AU de Lima, M
Porter, DL
Battiwalla, M
Bishop, MR
Giralt, SA
Hardy, NM
Kroger, N
Wayne, AS
Schmid, C
AF de Lima, Marcos
Porter, David L.
Battiwalla, Minoo
Bishop, Michael R.
Giralt, Sergio A.
Hardy, Nancy M.
Kroeger, Nicolaus
Wayne, Alan S.
Schmid, Christoph
TI Proceedings from the National Cancer Institute's Second International
Workshop on the Biology, Prevention, and Treatment of Relapse after
Hematopoietic Stem Cell Transplantation: Part III. Prevention and
Treatment of Relapse after Allogeneic Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Relapse; Stem cell transplantation; Prevention; Treatment; Allogeneic
ID ACUTE MYELOID-LEUKEMIA; DONOR LYMPHOCYTE INFUSIONS; ACUTE
LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL
DISEASE; VERSUS-HOST-DISEASE; T-CELLS; EX-VIVO; LEUKOCYTE INFUSIONS;
ENGAGING ANTIBODY
AB In the Second Annual National Cancer Institute's Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Prevention and Treatment of Relapse after Allogeneic Transplantation highlighted progress in developing new therapeutic approaches since the first relapse workshop. Recent insights that might provide a basis for the development of novel, practical clinical trials were emphasized, including utilization of newer agents, optimization of donor lymphocyte infusion (DLI), and investigation of novel cellular therapies. Dr. de Lima discussed pre-emptive and maintenance strategies to prevent relapse after transplantation, for example, recent promising results suggestive of enhanced graft-versus-tumor activity with hypomethylating agents. Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy for relapse, including cytoreduction before DLI, combination of targeted agents with DLI, and considerations in use of second transplantations. Dr. Porter addressed strategies to enhance T cell function, including ex vivo activated T cells and T cell engineering, and immunomodulatory approaches to enhance T cell function in vivo, including exogenous cytokines and modulation of costimulatory pathways. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [de Lima, Marcos] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Hematol Malignancies & Stem Cell Transplant Progr, Cleveland, OH 44106 USA.
[Porter, David L.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Battiwalla, Minoo] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Bishop, Michael R.] Univ Chicago Med, Hematol Oncol Sect, Chicago, IL USA.
[Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Hardy, Nancy M.] NCI, Expt Transplantat Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kroeger, Nicolaus] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany.
[Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Schmid, Christoph] Univ Munich, Klinikum Augsburg, Munich, Germany.
RP Hardy, NM (reprint author), NCI, Expt Transplantat Immunol Branch, Ctr Canc Res, Hatfield Clin Res Ctr, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM hardyn@mail.nih.gov
FU National Institutes of Health: the National Cancer Institute/Center for
Cancer Research; National Heart, Lung and Blood Institute; Novartis
FX Financial disclosure: Supported in part by the Intramural Research
Programs of the National Institutes of Health: the National Cancer
Institute/Center for Cancer Research and the National Heart, Lung and
Blood Institute.; Conflict of interest statement: The authors declare
the following financial relationships: M.L. has received consultancy
honoraria from Celgene. D.L.P. receives research support and has
potential future IP rights from patents and licensure to Novartis.
Conflict of interest was managed in accordance with University of
Pennsylvania policy and oversight.
NR 61
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JAN
PY 2014
VL 20
IS 1
BP 4
EP 13
DI 10.1016/j.bbmt.2013.08.012
PG 10
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 289LG
UT WOS:000329683400003
PM 24018392
ER
PT J
AU Shand, JC
Qin, HY
Nasholm, N
Capitini, CM
Fry, TJ
AF Shand, Jessica C.
Qin, Haiying
Nasholm, Nicole
Capitini, Christian M.
Fry, Terry J.
TI Minor Antigen Distribution Predicts Site-Specific Graft-versus-Tumor
Activity of Adoptively Transferred, Minor Antigen-Specific CD8 T Cells
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic transplantation; Minor histocompatibility antigens; Adoptive
T cell therapy; CD8 T cell function; Acute lymphoblastic leukemia
ID BONE-MARROW-TRANSPLANTATION; CHRONIC VIRAL-INFECTION; HISTOCOMPATIBILITY
ANTIGENS; HOST-DISEASE; MOUSE MODELS; SOLID TUMORS; LEUKEMIA;
EXHAUSTION; SURVIVAL; PROLIFERATION
AB The clinical success of allogeneic T cell therapy for cancer relies on the selection of antigens that can effectively elicit antitumor responses with minimal toxicity toward nonmalignant tissues. Although minor histocompatibility antigens (MiHA) represent promising targets, broad expression of these antigens has been associated with poor responses and T cell dysfunction that may not be prevented by targeting MiHA with limited expression. In this study, we hypothesized that antitumor activity of MiHA-specific CD8 T cells after allogeneic bone marrow transplantation (BMT) is determined by the distribution of antigen relative to the site of tumor growth. To test this hypothesis, we utilized the clinically relevant male-specific antigen HY and studied the fate of adoptively transferred, HY-CD8(+) T cells (HY-CD8) against a HY-expressing epithelial tumor (MB49) and pre-B cell leukemia (HY-E2APBX ALL) in BMT recipients. Transplants were designed to produce broad HY expression in nonhematopoietic tissues (female -> male BMT, [F -> M]), restricted HY expression in hematopoietic tissues (male -> female BMT, [M -> F]) tissues, and no HY tissue expression (female -> female BMT, [F -> F]). Broad HY expression induced poor responses to MB49 despite sublethal graft-versus-host disease and accumulation of HY-CD8 in secondary lymphoid tissues. Antileukemia responses, however, were preserved. In contrast, restriction of HY expression to hematopoietic tissues restored MB49 responses but resulted in a loss of antileukemia responses. We concluded that target alloantigen expression in the same compartment of tumor growth impairs CD8 responses to both solid and hematologic tumors. (C) 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Shand, Jessica C.; Qin, Haiying; Nasholm, Nicole; Fry, Terry J.] NCI, Blood & Marrow Transplant Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Capitini, Christian M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA.
[Capitini, Christian M.] Univ Wisconsin, Sch Med & Publ Hlth, UW Carbone Canc Ctr, Madison, WI USA.
RP Shand, JC (reprint author), Univ Rochester, Med Ctr, Div Pediat Hematol Oncol, 601 Elmwood Ave,Box 777, Rochester, NY 14642 USA.
EM Jessica_Shand@URMC.Rocnester.edu
OI Capitini, Christian/0000-0002-2276-6731
FU NIH
FX The authors thank Crystal Mackall and Daniel Fowler for their critical
review of the data and manuscript drafts. The GFP-conjugated male
E2APBX-ALL cell line was generously provided by Janet Bijil, Centre de
Recherche de l'Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada.
This work was supported by the NIH-T32 Training Grant "Laboratory
Training in Pediatric Hematology-Oncology", Principal Investigator
Donald Small, Johns Hopkins University.
NR 41
TC 6
Z9 6
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JAN
PY 2014
VL 20
IS 1
BP 26
EP 36
DI 10.1016/j.bbmt.2013.10.009
PG 11
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 289LG
UT WOS:000329683400006
PM 24141010
ER
PT J
AU Switzer, GE
Bruce, JG
Harrington, D
Haagenson, M
Drexler, R
Foley, A
Confer, D
Bishop, M
Anderlini, P
Rowley, S
Leitman, SF
Anasetti, C
Wingard, JR
AF Switzer, Galen E.
Bruce, Jessica G.
Harrington, Donna
Haagenson, Michael
Drexler, Rebecca
Foley, Amy
Confer, Dennis
Bishop, Michelle
Anderlini, Paolo
Rowley, Scott
Leitman, Susan F.
Anasetti, Claudio
Wingard, John R.
TI Health-related Quality of Life of Bone Marrow versus Peripheral Blood
Stem Cell Donors: A Prespecified Subgroup Analysis from a Phase III
RCT-BMTCTN Protocol 0201
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Marrow versus peripheral blood stem cell donation; Unrelated
hematopoietic stem cell donation; Randomized trial
ID UNRELATED DONORS; PROSPECTIVE TRIAL; MOOD STATES; DONATION; EXPERIENCE;
PROGRAM; TRANSPLANTATION; SAFETY; PRODUCT; PROFILE
AB Hematopoietic stem cells can be procured from unrelated donors via either the bone marrow (BM) aspiration or peripheral blood stem cell (PBSC) collection methods. There is no evidence from prospective randomized trials in the unrelated donor setting about the relative health-related quality-of-life (HRQoL) benefits/costs to donors. The goals of this prospective longitudinal investigation were to describe and compare the donation-related HRQoL experiences of 332 BM and PBSC donors. Donors were interviewed before donation, 48 hours after donation, weekly until fully recovered, and at 6 and 12 months after donation. Before donation, BM donors had lower confusion, fewer concerns, and were more prepared for donation. Shortly after donation, BM donors reported more physical side effects. BM donors also reported more donation-related impact on their social activities. However, BM donors reported somewhat better psychological status and were more likely to indicate that the donation made their lives more meaningful. There were virtually no longer term differences in the experiences of the 2 donor groups, including no recovery time difference beginning 3 weeks after donation. Although BM donors may experience the process as more physically stressful and more psychologically beneficial in the short term, the longer term HRQoL consequences of BM and PBSC donors are similar. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Switzer, Galen E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.
[Switzer, Galen E.; Bruce, Jessica G.; Harrington, Donna] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Switzer, Galen E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA 15213 USA.
[Haagenson, Michael; Drexler, Rebecca; Foley, Amy; Confer, Dennis] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Haagenson, Michael] Natl Marrow Donor Program, Minneapolis, MN USA.
[Bishop, Michelle; Wingard, John R.] Univ Florida, Coll Med, Gainesville, FL USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Rowley, Scott] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Leitman, Susan F.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Anasetti, Claudio] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
RP Switzer, GE (reprint author), Univ Pittsburgh, 3501 Forbes Ave,Oxford Bld Suite 410, Pittsburgh, PA 15213 USA.
EM SwitzerGE@upmc.edu
FU National Heart, Lung, and Blood Institute; National Cancer Institute
[U10HL069294]; Office of Naval Research; National Marrow Donor program
FX Financial disclosure: Supported by a grant from the National Heart,
Lung, and Blood Institute and the National Cancer Institute
(U10HL069294), by the Office of Naval Research, and by the National
Marrow Donor program.
NR 24
TC 9
Z9 9
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JAN
PY 2014
VL 20
IS 1
BP 118
EP 127
DI 10.1016/j.bbmt.2013.10.024
PG 10
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 289LG
UT WOS:000329683400018
PM 24184336
ER
PT J
AU Yu, MD
Tatalovich, Z
Gibson, JT
Cronin, KA
AF Yu, Mandi
Tatalovich, Zaria
Gibson, James T.
Cronin, Kathleen A.
TI Using a composite index of socioeconomic status to investigate health
disparities while protecting the confidentiality of cancer registry data
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE SEER; Socioeconomic index; Health disparity; Census tract; Cancer
incidence; Cancer survival
ID PROSTATE-CANCER; MORTALITY
AB The lack of individual socioeconomic status (SES) information in cancer registry data necessitates the use of area-based measures to investigate health disparities. Concerns about confidentiality, however, prohibit publishing patients' residential locations at the subcounty level. We developed a census tract-based composite SES index to be released in place of individual census tracts to minimize the risk of disclosure.
Two SES indices based on the measures identified in the literature were constructed using factor analysis. The analyses were repeated using the data from the 2000 decennial census and 2005-2009 American Community Survey to create the indices at two time points, which were linked to 2000-2009 Surveillance, Epidemiology, and End Results registry data to estimate incidence and survival rates.
The two indices performed similarly in stratifying census tracts and detecting socioeconomic gradients in cancer incidence and survival. The gradient in the incidence is positive for breast and prostate, and negative for lung cancers, in all races, although the level varies. The positive gradient in survival is more salient for regional-staged breast, colorectal, and lung cancers.
The census tract-based SES index provides a valuable tool for monitoring the disparities in cancer burdens while avoiding potential identity disclosure. This index, divided into tertiles and quintiles, is now available to the researchers on request.
C1 [Yu, Mandi; Tatalovich, Zaria; Cronin, Kathleen A.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Gibson, James T.] Informat Management Serv Inc, Silver Spring, MD USA.
RP Yu, MD (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD USA.
EM yum3@mail.nih.gov
NR 21
TC 9
Z9 10
U1 2
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JAN
PY 2014
VL 25
IS 1
BP 81
EP 92
DI 10.1007/s10552-013-0310-1
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 284WG
UT WOS:000329351700008
PM 24178398
ER
PT J
AU Tanimoto, K
Muranski, P
Miner, S
Fujiwara, H
Kajigaya, S
Keyvanfar, K
Hensel, N
Barrett, AJ
Melenhorst, JJ
AF Tanimoto, Kazushi
Muranski, Pawel
Miner, Samantha
Fujiwara, Hiroshi
Kajigaya, Sachiko
Keyvanfar, Keyvan
Hensel, Nancy
Barrett, A. John
Melenhorst, J. Joseph
TI Genetically engineered fixed K562 cells: potent "off-the-shelf"
antigen-presenting cells for generating virus-specific T cells
SO CYTOTHERAPY
LA English
DT Article
DE artificial APC; cytomegalovirus; cytotoxic T cell; fixation
ID ACUTE MYELOID-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; DENDRITIC CELLS; BK
VIRUS; LYMPHOCYTES; RESPONSES; EXPRESSION; EXPANSION; THERAPY; 4-1BB
AB Background aims. The human leukemia cell line K562 represents an attractive platform for creating artificial antigen-presenting cells (aAPC). It is readily expandable, does not express human leukocyte antigen (HLA) class I and II and can be stably transduced with various genes. Methods. In order to generate cytomegalovirus (CMV) antigen-specific T cells for adoptive immunotherapy, we transduced K562 with HLA-A*0201 in combination with co-stimulatory molecules. Results. In preliminary experiments, irradiated K562 expressing HLA-A*0201 and 4-1BBL pulsed with CMV pp65 and IE-1 peptide libraries failed to elicit antigen-specific CD8(+) T cells in HLA-A*0201(+) peripheral blood mononuclear cells (PBMC) or isolated T cells. Both wild-type K62 and aAPC strongly inhibited T cell proliferation to the bacterial superantigen staphylococcal enterotoxin B (SEB) and OKT3 and in mixed lymphocyte reaction (MLR). Transwell experiments suggested that suppression was mediated by a soluble factor; however, MLR inhibition was not reversed using transforming growth factor-beta blocking antibody or prostaglandin E-2 inhibitors. Full abrogation of the suppressive activity of K562 on MLR, SEB and OKT3 stimulation was only achieved by brief fixation with 0.1% formaldehyde. Fixed, pp65 and IE-1 peptide-loaded aAPC induced robust expansion of CMV-specific T cells. Conclusions. Fixed gene-modified K562 can serve as effective aAPC to expand CMV-specific cytotoxic T lymphocytes for therapeutic use in patients after stem cell transplantation. Our findings have implications for broader understanding of the immune evasion mechanisms used by leukemia and other tumors.
C1 [Tanimoto, Kazushi; Muranski, Pawel; Miner, Samantha; Kajigaya, Sachiko; Keyvanfar, Keyvan; Hensel, Nancy; Barrett, A. John; Melenhorst, J. Joseph] NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Fujiwara, Hiroshi] Ehime Univ, Grad Sch Med, Dept Bioregulatory Med, Matsuyama, Ehime 790, Japan.
[Melenhorst, J. Joseph] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
RP Tanimoto, K (reprint author), NHLBI, Stem Cell Allogene Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM kazshi.tanimoto@gmail.com
NR 42
TC 2
Z9 2
U1 1
U2 9
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JAN
PY 2014
VL 16
IS 1
BP 135
EP 146
DI 10.1016/j.jcyt.2013.08.008
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 288DS
UT WOS:000329592800014
PM 24176543
ER
PT J
AU Miller, DS
AF Miller, David S.
TI REGULATION OF ABC TRANSPORTERS AT THE BLOOD-BRAIN AND BLOOD-SPINAL CORD
BARRIERS
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 10th International Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY SEP 29-OCT 03, 2013
CL Toronto, CANADA
SP Int Soc Study Xenobiot
C1 [Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD JAN
PY 2014
VL 45
SU 1
BP 7
EP 7
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 286DO
UT WOS:000329445700016
ER
PT J
AU Gonzalez, FJ
AF Gonzalez, Frank J.
TI PREGNANE X RECEPTOR AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR alpha
HUMANIZED MICE
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 10th International Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY SEP 29-OCT 03, 2013
CL Toronto, CANADA
SP Int Soc Study Xenobiot
C1 [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD JAN
PY 2014
VL 45
SU 1
BP 20
EP 20
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 286DO
UT WOS:000329445700048
ER
PT J
AU Gotoh, S
Negishi, M
AF Gotoh, Saki
Negishi, Masahiko
TI PXR IS A LIGAND-ACTIVATED SIGNAL SCAFFOLD THAT FACILITATES PP2C
DEPHOSPHORYLATING SGK2 TO REGULATE HEPATIC GLUCONEOGENESIS
SO DRUG METABOLISM REVIEWS
LA English
DT Meeting Abstract
CT 10th International Meeting of the
International-Society-for-the-Study-of-Xenobiotics (ISSX)
CY SEP 29-OCT 03, 2013
CL Toronto, CANADA
SP Int Soc Study Xenobiot
C1 [Gotoh, Saki; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD JAN
PY 2014
VL 45
SU 1
BP 145
EP 145
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 286DO
UT WOS:000329445700292
ER
PT J
AU Lee, D
Huestis, MA
AF Lee, Dayong
Huestis, Marilyn A.
TI Current knowledge on cannabinoids in oral fluid
SO DRUG TESTING AND ANALYSIS
LA English
DT Review
DE oral fluid; cannabis; delta-9-tetrahydrocannabinol; marijuana; saliva;
cannabinoid
ID TANDEM MASS-SPECTROMETRY; ILLICIT DRUG-USE; PERFORMANCE
LIQUID-CHROMATOGRAPHY; CONTROLLED SMOKED CANNABIS; SOLID-PHASE
EXTRACTION; EXTERNAL QUALITY ASSESSMENT; POSITIVE PREVALENCE RATES;
RANDOMLY SELECTED DRIVERS; MOTOR-VEHICLE CRASHES; CHRONIC PAIN PATIENTS
AB Oral fluid (OF) is a new biological matrix for clinical and forensic drug testing, offering non-invasive and directly observable sample collection reducing adulteration potential, ease of multiple sample collections, lower biohazard risk during collection, recent exposure identification, and stronger correlation with blood than urine concentrations. Because cannabinoids are usually the most prevalent analytes in illicit drug testing, application of OF drug testing requires sufficient scientific data to support sensitive and specific OF cannabinoid detection. This review presents current knowledge of OF cannabinoids, evaluating pharmacokinetic properties, detection windows, and correlation with other biological matrices and impairment from field applications and controlled drug administration studies. In addition, onsite screening technologies, confirmatory analytical methods, drug stability, and effects of sample collection procedure, adulterants, and passive environmental exposure are reviewed. Delta-9-tetrahydrocannabinol OF concentrations could be >1000 mu g/L shortly after smoking, whereas minor cannabinoids are detected at 10-fold and metabolites at 1000-fold lower concentrations. OF research over the past decade demonstrated that appropriate interpretation of test results requires a comprehensive understanding of distinct elimination profiles and detection windows for different cannabinoids, which are influenced by administration route, dose, and drug use history. Thus, each drug testing program should establish cut-off criteria, collection/analysis procedures, and storage conditions tailored to its purposes. Building a scientific basis for OF testing is ongoing, with continuing OF cannabinoids research on passive environmental exposure, drug use history, donor physiological conditions, and oral cavity metabolism needed to better understand mechanisms of cannabinoid OF disposition and expand OF drug testing applicability. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Lee, Dayong; Huestis, Marilyn A.] Natl Inst Drug Abuse, Natl Inst Hlth, Chem & Drug Metab Intramural Res Program, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, IRP, NIH, Biomed Res Ctr, 251 Bayview Blvd Suite 200,Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program, National Institute on Drug Abuse, NIH
FX This research was funded by Intramural Research Program, National
Institute on Drug Abuse, NIH.
NR 246
TC 16
Z9 16
U1 6
U2 52
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1942-7603
EI 1942-7611
J9 DRUG TEST ANAL
JI Drug Test. Anal.
PD JAN
PY 2014
VL 6
IS 1-2
SI SI
BP 88
EP 111
DI 10.1002/dta.1514
PG 24
WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA 287QE
UT WOS:000329556500012
PM 23983217
ER
PT J
AU Armstrong, AC
Gjesdal, O
Almeida, A
Nacif, M
Wu, C
Bluemke, DA
Brumback, L
Lima, JAC
AF Armstrong, Anderson C.
Gjesdal, Ola
Almeida, Andre
Nacif, Marcelo
Wu, Colin
Bluemke, David A.
Brumback, Lyndia
Lima, Joao A. C.
TI Left Ventricular Mass and Hypertrophy by Echocardiography and Cardiac
Magnetic Resonance: The Multi-Ethnic Study of Atherosclerosis
SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED
TECHNIQUES
LA English
DT Article
DE left ventricular mass; left ventricular hypertrophy; echocardiography;
image quality
ID SOCIETY-OF-CARDIOLOGY; CARDIOVASCULAR RISK; BODY-SIZE; HYPERTENSION;
REGRESSION; AGE; QUANTIFICATION; POPULATION; GUIDELINES; DISEASE
AB BackgroundLeft ventricular mass (LVM) and hypertrophy (LVH) are important parameters, but their use is surrounded by controversies. We compare LVM by echocardiography and cardiac magnetic resonance (CMR), investigating reproducibility aspects and the effect of echocardiography image quality. We also compare indexing methods within and between imaging modalities for classification of LVH and cardiovascular risk.
MethodsMulti-Ethnic Study of Atherosclerosis enrolled 880 participants in Baltimore city, 146 had echocardiograms and CMR on the same day. LVM was then assessed using standard techniques. Echocardiography image quality was rated (good/limited) according to the parasternal view. LVH was defined after indexing LVM to body surface area, height(1.7), height(2.7), or by the predicted LVM from a reference group. Participants were classified for cardiovascular risk according to Framingham score. Pearson's correlation, Bland-Altman plots, percent agreement, and kappa coefficient assessed agreement within and between modalities.
ResultsLeft ventricular mass by echocardiography (14040g) and by CMR were correlated (r=0.8, P<0.001) regardless of the echocardiography image quality. The reproducibility profile had strong correlations and agreement for both modalities. Image quality groups had similar characteristics; those with good images compared to CMR slightly superiorly. The prevalence of LVH tended to be higher with higher cardiovascular risk. The agreement for LVH between imaging modalities ranged from 77% to 98% and the kappa coefficient from 0.10 to 0.76.
ConclusionsEchocardiography has a reliable performance for LVM assessment and classification of LVH, with limited influence of image quality. Echocardiography and CMR differ in the assessment of LVH, and additional differences rise from the indexing methods.
C1 [Armstrong, Anderson C.; Gjesdal, Ola; Almeida, Andre; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21287 USA.
[Armstrong, Anderson C.] Univ Sao Francisco Valley, Sch Med, Petrolina, PE, Brazil.
[Nacif, Marcelo; Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Wu, Colin] NHLBI, NIH, Bethesda, MD 20892 USA.
[Brumback, Lyndia] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Div Cardiol, 600 N Wolfe St,Blalock 524D1, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Armstrong, Anderson/G-8407-2012; Gjesdal, Ola/C-1941-2015;
OI Armstrong, Anderson/0000-0003-3161-8922; Gjesdal,
Ola/0000-0003-1913-6445; Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute NHLBI; MESA [RO1-HL-66075,
NO1-HC-9808, N01-HC-95162, NO1-HC-95168, NO1-HC-95169]; Universidade
Federal do Vale do Sao Francisco UNIVASF, Petrolina, PE, Brazil
FX The study was funded by the National Heart, Lung, and Blood Institute
NHLBI supported by the MESA study contracts RO1-HL-66075, NO1-HC-9808,
N01-HC-95162, NO1-HC-95168, and NO1-HC-95169. Dr. Armstrong was funded
by Universidade Federal do Vale do Sao Francisco UNIVASF, Petrolina, PE,
Brazil.
NR 28
TC 9
Z9 9
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-2822
EI 1540-8175
J9 ECHOCARDIOGR-J CARD
JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech.
PD JAN
PY 2014
VL 31
IS 1
BP 12
EP 20
DI 10.1111/echo.12303
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 282TS
UT WOS:000329197100015
PM 23930739
ER
PT J
AU Lendvai, N
Pawlosky, R
Bullova, P
Eisenhofer, G
Patocs, A
Veech, RL
Pacak, K
AF Lendvai, Nikoletta
Pawlosky, Robert
Bullova, Petra
Eisenhofer, Graeme
Patocs, Attila
Veech, Richard L.
Pacak, Karel
TI Succinate-to-Fumarate Ratio as a New Metabolic Marker to Detect the
Presence of SDHB/D-related Paraganglioma: Initial Experimental and Ex
Vivo Findings
SO ENDOCRINOLOGY
LA English
DT Article
ID HEREDITARY PARAGANGLIOMA; TUMOR SUPPRESSORS; GENE-MUTATIONS;
PHEOCHROMOCYTOMA; DEHYDROGENASE; HYPOXIA; SUBUNIT; SDHC; TUMORIGENESIS;
ACTIVATION
AB Pheochromocytomas (PHEOs) and paragangliomas (PGLs; extra-adrenal tumors) are rare neuroendocrine chromaffin cell tumors with a hereditary background in about 30%-35%. Those caused by succinate dehydrogenase subunit B (SDHB) germline mutations are associated with a high metastatic potential and ultimately higher patient mortality. Succinate dehydrogenase converts succinate to fumarate, uniquely linking the Krebs cycle and oxidative phosphorylation. SDH mutations result in the accumulation of succinate associated with various metabolic disturbances and the shift to aerobic glycolysis in tumor tissue. In the present study, we measured succinate and fumarate levels in mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells and in 10 apparently sporadic, 10 SDHB-, 5 SDHD-, and 2 neurofibromatosis 1-related PHEOs/PGLs and plasma samples using mass spectrometry. We found that the succinate-to-fumarate ratio was significantly higher in the SDHB- and SDHD-related PGLs than in apparently sporadic and neurofibromatosis 1-related PHEOs/PGLs (P = .0376). To further support our data, we silenced SDHB expression in MPC and MTT cells and evaluated the succinate and fumarate levels. Compared with control samples, SDHB-silenced MTT cells also showed an increase in the succinate-to-fumarate ratio (MTT cells: 2.45 vs 7.53), similar to the findings in SDHB-related PGLs. The present findings for the first time demonstrate a significantly increased succinate-to-fumarate ratio in SDHB/D-related PGLs and thus suggest this ratio may be used as a new metabolic marker for the detection of SDHB/D-related PHEOs/PGLs.
C1 [Lendvai, Nikoletta; Bullova, Petra; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Lendvai, Nikoletta] Semmelweis Univ, Dept Med 2, H-1088 Budapest, Hungary.
[Pawlosky, Robert; Veech, Richard L.] NIAAA, Sect Metab Control Anal, NIH, Rockville, MD 20852 USA.
[Bullova, Petra] Slovak Acad Sci, Inst Virol, Dept Mol Med, Bratislava 84505, Slovakia.
[Eisenhofer, Graeme] Univ Hosp Carl Gustav Carus TU Dresden, Inst Clin Chem & Lab Med, Dresden, Germany.
[Eisenhofer, Graeme] Univ Hosp Carl Gustav Carus TU Dresden, Dept Med 3, D-01307 Dresden, Germany.
[Patocs, Attila] Hungarian Acad Sci, Mol Med Res Grp, Budapest, Hungary.
[Patocs, Attila] Semmelweis Univ, H-1085 Budapest, Hungary.
[Patocs, Attila] Semmelweis Univ, Cent Isotope Lab, Dept Lab, Inst Med, H-1088 Budapest, Hungary.
RP Pacak, K (reprint author), Eunice Kennedy Shriver NICHD, Sect Med Neuroendocrinol, NIH, Bldg 10 CRC,1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
NR 27
TC 20
Z9 21
U1 0
U2 13
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD JAN
PY 2014
VL 155
IS 1
BP 27
EP 32
DI 10.1210/en.2013-1549
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 279NU
UT WOS:000328967500007
PM 24189137
ER
PT J
AU Neumann, S
Nir, EA
Eliseeva, E
Huang, WW
Marugan, J
Xiao, JB
Dulcey, AE
Gershengorn, MC
AF Neumann, Susanne
Nir, Eshel A.
Eliseeva, Elena
Huang, Wenwei
Marugan, Juan
Xiao, Jingbo
Dulcey, Andres E.
Gershengorn, Marvin C.
TI A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid
Function in Female Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID THYROTROPIN RECEPTOR; INVERSE AGONIST; GRAVES OPHTHALMOPATHY; ORBITAL
FIBROBLASTS; HORMONE-RECEPTOR; CAMP PRODUCTION; DISEASE; SUPPRESSION;
MECHANISMS; ANTIBODY
AB Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T-4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 mu M for TSHR and greater than 30 mu M for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T-4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T-4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.
C1 [Neumann, Susanne; Nir, Eshel A.; Eliseeva, Elena; Gershengorn, Marvin C.] Natl Inst Diabet & Digest & Kidney Dis, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andres E.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), Natl Inst Diabet & Digest & Kidney Dis, NIH, Lab Endocrinol & Receptor Biol, 50 South Dr, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU Intramural Research Program of the National Institutes of Health [1 Z01
DK047044]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (Grant 1 Z01 DK047044).
NR 18
TC 19
Z9 23
U1 0
U2 4
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD JAN
PY 2014
VL 155
IS 1
BP 310
EP 314
DI 10.1210/en.2013-1835
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 279NU
UT WOS:000328967500034
PM 24169564
ER
PT J
AU Quick, V
Lipsky, LM
Laffel, LMB
Mehta, SN
Quinn, H
Nansel, TR
AF Quick, V.
Lipsky, L. M.
Laffel, L. M. B.
Mehta, S. N.
Quinn, H.
Nansel, T. R.
TI Relationships of neophobia and pickiness with dietary variety, dietary
quality and diabetes management adherence in youth with type 1 diabetes
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE dietary variety; dietary quality; neophobia; pickiness; type 1 diabetes;
youth
ID CHILDRENS FOOD PREFERENCES; CORONARY-HEART-DISEASE; BODY-MASS INDEX;
CHILDHOOD; ADOLESCENTS; ACCEPTANCE; CONSUMPTION; VALIDATION; ADULTS;
PREDICTORS
AB BACKGROUND/OBJECTIVES: Neophobia, pickiness and diet variety are associated with diet quality and health outcomes in young children. Limited research has examined these associations among youth with type 1 diabetes (T1D), a population at risk for poor health outcomes when dietary quality is inadequate.
SUBJECTS/METHODS: Youth (n = 252, age 13.2 +/- 2.8 years, 92% white, diabetes duration 6.3 +/- 3.4 years) with T1D and their parents completed 3-day youth diet records; parents completed questionnaires regarding youth neophobia, pickiness and diabetes management adherence. Medical records provided biomedical data. Dietary quality indicators included Nutrient-Rich Foods Index 9.3 (NRF9.3), Healthy Eating Index-2005 (HEI-2005), Whole Plant Food Density (WPFD) and key single nutrients. Dietary variety was operationalized as a count of 20 recommended food groups consumed. Relationships of dietary quality and diabetes management adherence with neophobia, pickiness and dietary variety as independent variables were examined using multiple linear regression analyses adjusted for total energy intake, age, height and weight.
RESULTS: In multiple linear regression analyses, NRF9.3 and HEI-2005 were each inversely associated with neophobia and pickiness, and positively associated with dietary variety. WPF and potassium were each positively associated and saturated fat was inversely associated with dietary variety. However, in models simultaneously including neophobia, pickiness and dietary variety as independent correlates of dietary quality, only relationships with dietary variety remained significant. Diabetes management adherence was negatively associated with both neophobia and pickiness and positively associated with dietary variety.
CONCLUSIONS: Findings suggest that increasing dietary variety may contribute toward improved dietary quality among youth with T1D, despite potentially adverse influences of neophobia and pickiness.
C1 [Quick, V.; Lipsky, L. M.; Nansel, T. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Laffel, L. M. B.; Mehta, S. N.; Quinn, H.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect,Pediat Adolescent & Young, Boston, MA 02115 USA.
RP Quick, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, US Dept HHS, 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM gingermquick@gmail.com
OI Quick, Virginia/0000-0002-4338-963X; Nansel, Tonja/0000-0002-8298-7595;
Lipsky, Leah/0000-0003-2645-4388
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN267200703434C]
FX This research was supported by the intramural research program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, Contract Number
HHSN267200703434C.
NR 49
TC 5
Z9 5
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
EI 1476-5640
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD JAN
PY 2014
VL 68
IS 1
BP 131
EP 136
DI 10.1038/ejcn.2013.239
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 285ZL
UT WOS:000329433900024
PM 24253761
ER
PT B
AU Martin, WJ
Hollingsworth, JW
Ramanathan, V
AF Martin, William J., II
Hollingsworth, John W.
Ramanathan, Veerabhadran
BE Pinkerton, KE
Rom, WN
TI Household Air Pollution from Cookstoves: Impacts on Health and Climate
SO GLOBAL CLIMATE CHANGE AND PUBLIC HEALTH
SE Respiratory Medicine Series
LA English
DT Article; Book Chapter
DE Biomass; Household air pollution; Climate change; Poverty and climate
change
ID ATMOSPHERIC BROWN CLOUDS; BLACK CARBON; DNA METHYLATION; BIOMASS
COOKSTOVES; GLOBAL BURDEN; RISK-FACTORS; LUNG-CANCER; EXPOSURE; INDIA;
DISEASE
AB Household air pollution (HAP) is an exposure of poverty. The success in having a sustainable reduction in HAP requires an understanding of the traditions and culture of the family as well as the causes of poverty that place the family at the bottom of the energy ladder. An integrated approach to reducing HAP with efforts also aimed at correcting other poverty-related issues is challenging but offers the hope for addressing root causes of poverty in a community setting that provides a more comprehensive and sustainable approach to improving health, the environment, and, ultimately, the global climate. From one perspective, research that provides detailed exposure-responses to HAP may seem superfluous to the obvious need for poor families to breathe cleaner air at home. One can argue that we already have decades of information on the health risks from outdoor air pollution or the products of incomplete combustion from tobacco smoke and so further research is not needed. However, there is a compelling need to know how clean a stove or fuel must be to significantly reduce health risks, so that with proper use, major implementation of such new technology may reasonably provide the intended benefits for improved health, the regional environment, and the global climate. The alternative of providing electrification or use of clean fuels such as LPG may not be realistic for the world's poor for decades to come, if ever. Addressing the key scientific gaps related to HAP and its reduction will provide critical new information that can inform large scale implementation programs to provide sufficiently clean household air for families living in poverty, such that diseases are prevented, a healthier lifestyle is promoted, and a reduction in global warming trends buys more time for a planet in peril from climate change.
C1 [Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Hollingsworth, John W.] Duke Univ Med Ctr, Dept Med & Immunol, Durham, NC 27710 USA.
[Ramanathan, Veerabhadran] Scripps Inst Oceanog, Ctr Atmospher Sci, La Jolla, CA 92037 USA.
[Ramanathan, Veerabhadran] Univ Calif San Diego, La Jolla, CA 92093 USA.
RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 31 Ctr Dr,Bldg 31,Room 2A32,MSC 2425, Bethesda, MD 20892 USA.
EM wjmartin@mail.nih.gov
NR 65
TC 4
Z9 4
U1 2
U2 9
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-1-4614-8417-2; 978-1-4614-8416-5
J9 RESPIR MED SER
PY 2014
VL 7
BP 237
EP 255
DI 10.1007/978-1-4614-8417-2_13
D2 10.1007/978-1-4614-8417-2
PG 19
WC Environmental Sciences; Public, Environmental & Occupational Health;
Respiratory System
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Respiratory System
GA BJJ05
UT WOS:000328380700014
ER
PT B
AU Levine, M
Balbus, J
AF Levine, Maya
Balbus, John
BE Pinkerton, KE
Rom, WN
TI Federal Programs in Climate Change and Health Research
SO GLOBAL CLIMATE CHANGE AND PUBLIC HEALTH
SE Respiratory Medicine Series
LA English
DT Article; Book Chapter
DE Federal programs in climate change and health research; Health research
and climate change; Climate change and federal programs; Research in
climate change; Global Change Research Program
AB The federal government plays an integral role in supporting climate change science and health research in the USA. Federally funded climate change research initially focused on science to understand climate and earth systems change during the 1970s and 1980s. Today, federally supported climate change research involves numerous agencies pursuing a wide range of climate change science topics and applications, including research exploring the connections between human health and climate change. Because each federal agency has a different mandate and range of scientific expertise, the focus and goals of various agencies' climate change and human health research vary. For example, the National Oceanic and Atmospheric Administration (NOAA) emphasizes the use of weather and climate forecasts and oceanographic data for public health applications, while the National Aeronautics and Space Administration (NASA) emphasizes health applications of remotely sensed data from its satellites. This chapter provides a brief history of federally funded climate research and includes a survey of the relevant agencies, programs, tools, and datasets to illustrate the diversity of health and climate change research supported by the federal government.
C1 [Levine, Maya; Balbus, John] NIEHS, Bethesda, MD 20892 USA.
RP Balbus, J (reprint author), NIEHS, 31 Ctr Dr,Room B1C02, Bethesda, MD 20892 USA.
EM balbusjm@niehs.nih.gov
NR 31
TC 0
Z9 0
U1 1
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
BN 978-1-4614-8417-2; 978-1-4614-8416-5
J9 RESPIR MED SER
PY 2014
VL 7
BP 319
EP 340
DI 10.1007/978-1-4614-8417-2_19
D2 10.1007/978-1-4614-8417-2
PG 22
WC Environmental Sciences; Public, Environmental & Occupational Health;
Respiratory System
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Respiratory System
GA BJJ05
UT WOS:000328380700020
ER
PT J
AU Opletalova, K
Bourillon, A
Yang, W
Pouvelle, C
Armier, J
Despras, E
Martin, L
Mateus, C
Robert, C
Kannouche, P
Soufir, N
Sarasin, A
AF Opletalova, Kristina
Bourillon, Agnes
Yang, Wei
Pouvelle, Caroline
Armier, Jacques
Despras, Emmanuelle
Martin, Ludovic
Mateus, Christine
Robert, Caroline
Kannouche, Patricia
Soufir, Nadem
Sarasin, Alain
TI Correlation of Phenotype/Genotype in a Cohort of 23 Xeroderma
Pigmentosum-Variant Patients Reveals 12 New Disease-Causing POLH
Mutations
SO HUMAN MUTATION
LA English
DT Article
DE DNA repair; UV; trans-lesion polymerases; skin cancers; melanomas; POLH
ID DNA-POLYMERASE-ETA; TRANSLESION SYNTHESIS; MOLECULAR ANALYSIS; JAPANESE
PATIENTS; HUMAN-CELLS; GENE; REPAIR; HYPERMUTATION; REPLICATION;
MECHANISM
AB Xeroderma pigmentosum variant (XP-V) is a rare genetic disease, characterized by some sunlight sensitivity and predisposition to cutaneous malignancies. We described clinical and genetic features of the largest collection ever published of 23 XP-V patients (ages between 21 and 86) from 20 unrelated families. Primary fibroblasts from patients showed normal nucleotide excision repair but UV-hypersensitivity in the presence of caffeine, a signature of the XP-V syndrome. 87% of patients developed skin tumors with a median age of 21 for the first occurrence. The median numbers of basal-cell carcinoma was 13 per patient, six for squamous-cell carcinoma, and five for melanoma. XP-V is due to defects in the translesion-synthesis DNA polymerase Pol coded by the POLH gene. DNA sequencing of POLH revealed 29 mutations, where 12 have not been previously identified, leading to truncated polymerases in 69% of patients. Four missense mutations are correlated with the protein stability by structural modeling of the Pol polymerase domain. There is a clear relationship between the types of missense mutations and clinical severity. For truncating mutations, which lead to an absence of or to inactive proteins, the life-cumulated UV exposure is probably the best predictor of cancer incidence, reinforcing the necessity to protect XP-Vs from sun exposure. (C) 2013 Wiley Periodicals, Inc.
C1 [Opletalova, Kristina; Pouvelle, Caroline; Armier, Jacques; Despras, Emmanuelle; Kannouche, Patricia; Sarasin, Alain] Univ Paris 11, CNRS, UMR8200, Lab Genet Stabil & Oncogenesis, Villejuif, France.
[Opletalova, Kristina; Pouvelle, Caroline; Armier, Jacques; Despras, Emmanuelle; Kannouche, Patricia; Sarasin, Alain] Inst Gustave Roussy, F-94805 Villejuif, France.
[Opletalova, Kristina; Mateus, Christine; Robert, Caroline] Inst Gustave Roussy, Dept Dermatol, F-94805 Villejuif, France.
[Bourillon, Agnes; Soufir, Nadem] Hop Bichat Claude Bernard, APHP, Genet Lab, F-75877 Paris, France.
[Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Pouvelle, Caroline; Despras, Emmanuelle; Kannouche, Patricia] Univ Paris 11, Equipe Labellisee Ligue Canc TLS Polymerases & Ca, Villejuif, France.
[Pouvelle, Caroline; Despras, Emmanuelle; Kannouche, Patricia] Inst Cancerol Gustave Roussy, Villejuif, France.
[Martin, Ludovic] CHU Angers, Serv Dermatol, Angers, France.
[Soufir, Nadem] Hop St Louis, APHP, INSERM, U976,Ctr Rech Peau, Paris, France.
[Soufir, Nadem] Univ Paris, F-75252 Paris, France.
[Sarasin, Alain] Inst Gustave Roussy, Dept Genet, F-94805 Villejuif, France.
RP Sarasin, A (reprint author), Inst Gustave Roussy, CNRS, UMR8200, PR2,114,Rue Edouard Vaillant, F-94805 Villejuif, France.
EM alain.sarasin@gustaveroussy.fr
RI Yang, Wei/D-4926-2011; Martin, Ludovic/K-2674-2015
OI Yang, Wei/0000-0002-3591-2195;
FU Centre National de la Recherche Scientifique (Paris, France); Agence
Nationale pour la Recherche (Paris); Association des Enfants de la Lune
(Tercis, France); La Ligue Nationale contre le Cancer ("Equipe
labellisee"), Paris, France; Institut National du Cancer (INCa), Paris;
Agence Nationale de la Recherche, Paris [ANR-09-PIRI-001]
FX Contract grant sponsors: Centre National de la Recherche Scientifique
(Paris, France); the Agence Nationale pour la Recherche (Paris); the
Association des Enfants de la Lune (Tercis, France); La Ligue Nationale
contre le Cancer ("Equipe labellisee"), Paris, France; the Institut
National du Cancer (INCa, PLBio-2010), Paris; the Agence Nationale de la
Recherche (No ANR-09-PIRI-001), Paris.
NR 31
TC 7
Z9 8
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD JAN
PY 2014
VL 35
IS 1
BP 117
EP 128
DI 10.1002/humu.22462
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 289JP
UT WOS:000329678600016
PM 24130121
ER
PT J
AU Lokanga, RA
Zhao, XN
Usdin, K
AF Lokanga, Rachel Adihe
Zhao, Xiao-Nan
Usdin, Karen
TI The Mismatch Repair Protein MSH2 is Rate Limiting for Repeat Expansion
in a Fragile X Premutation Mouse Model
SO HUMAN MUTATION
LA English
DT Article
DE fragile X-related disorders; FXTAS; FXPOI; triplet repeat expansion;
mismatch repair; MMR; MSH2
ID DM1 TRANSGENIC MICE; MUTS HOMOLOG 2; KNOCK-IN MICE; FMR1 GENE;
TRINUCLEOTIDE REPEAT; FULL MUTATION; SOMATIC EXPANSION; TRIPLET REPEAT;
DEFICIENT MICE; CAG REPEAT
AB Fragile X-associated tremor and ataxia syndrome, Fragile X-associated primary ovarian insufficiency, and Fragile X syndrome are Repeat Expansion Diseases caused by expansion of a CGG center dot CCG-repeat microsatellite in the 5 UTR of the FMR1 gene. To help understand the expansion mechanism responsible for these disorders, we have crossed mice containing approximate to 147 CGG center dot CCG repeats in the endogenous murine Fmr1 gene with mice containing a null mutation in the gene encoding the mismatch repair protein MSH2. MSH2 mutations are associated with elevated levels of generalized microsatellite instability. However, we show here for the first time that in the FX mouse model, all maternally and paternally transmitted expansions require Msh2. Even the loss of one Msh2 allele reduced the intergenerational expansion frequency significantly. Msh2 is also required for all somatic expansions and loss of even one functional Msh2 allele reduced the extent of somatic expansion in some organs. Tissues with lower levels of MSH2 were more sensitive to the loss of a single Msh2 allele. This suggests that MSH2 is rate limiting for expansion in this mouse model and that MSH2 levels may be a key factor that accounts for tissue-specific differences in expansion risk. Published 2013 Wiley Periodicals, Inc.
C1 [Lokanga, Rachel Adihe; Zhao, Xiao-Nan; Usdin, Karen] NIDDK, Sect Genom Struct & Funct, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Lokanga, Rachel Adihe] Univ Cape Town, Div Med Biochem, ZA-7925 Cape Town, South Africa.
RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr DR MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
RI Zhao, Xiaonan/S-3139-2016
FU Intramural Program of NIH (NIDDK) [DK057808-05]
FX Contract grant sponsor: Intramural Program of NIH (NIDDK) (DK057808-05).
NR 50
TC 24
Z9 24
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD JAN
PY 2014
VL 35
IS 1
BP 129
EP 136
DI 10.1002/humu.22464
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 289JP
UT WOS:000329678600017
PM 24130133
ER
PT J
AU Ribeiro, JMC
Chagas, AC
Pham, VM
Lounibos, LP
Calvo, E
AF Ribeiro, Jose M. C.
Chagas, Andrezza C.
Pham, Van M.
Lounibos, L. P.
Calvo, Eric
TI An insight into the sialome of the frog biting fly, Corethrella
appendiculata
SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Evolution; Culicomorpha; Corethrellidae; Salivary gland; Hematophagy;
Medical entomology
ID MOSQUITO AEDES-AEGYPTI; SEQUENCE ALIGNMENT; ANOPHELES-GAMBIAE;
RANA-CATESBEIANA; SALIVARY-GLANDS; O-GLYCOSYLATION; YELLOW-FEVER;
DIPTERA; THROMBOCYTES; PROTEIN
AB The Nematocera infraorder Culicomorpha is believed to have descended from bloodfeeding ancestors over 200 million years ago, generating bloodfeeding and non-bloodfeeding flies in two superfamilies, the Culicoidea-containing the mosquitoes, the frog-feeding midges, the Chaoboridae, and the Dixidae-and the Chironomoidea-containing the black flies, the ceratopogonids, the Chironomidae, and the Thaumaleidae. Bloodfeeding requires many adaptations, including development of a sophisticated salivary potion that disarms host hemostasis, the physiologic mechanism comprising platelet aggregation, vasoconstriction, and blood clotting. The composition of the sialome (from the Greek sialo = saliva) from bloodfeeding animals can be inferred from analysis of their salivary gland transcriptome. While members of the mosquitoes, black flies, and biting midges have provided sialotranscriptome descriptions, no species of the frog-biting midges has been thus analyzed. We describe in this work the sialotranscriptome of Corethrella appendiculata, revealing a complex potion of enzymes, classical nematoceran protein families involved in bloodfeeding, and novel protein families unique to this species of frog-feeding fly. Bacterial (Wolbachia) and novel viral sequences were also discovered. Published by Elsevier Ltd.
C1 [Ribeiro, Jose M. C.; Chagas, Andrezza C.; Pham, Van M.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Lounibos, L. P.] Univ Florida, Florida Med Entomol Lab, Vero Beach, FL 32962 USA.
RP Ribeiro, JMC (reprint author), NIAID, Vector Biol Sect, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 2E-32D, Rockville, MD 20852 USA.
EM jribeiro@niaid.nih.gov
RI Ribeiro, Jose/J-7011-2015;
OI Calvo, Eric/0000-0001-7880-2730; Ribeiro, Jose/0000-0002-9107-0818
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, USA; NIH [R01
AI044793, R21 AI095780]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA, and by NIH grants R01 AI044793 and R21 AI095780 to L.P.L.
We thank B. R. Marshall, DPSS, NIAID, for editing.
NR 83
TC 10
Z9 10
U1 0
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0965-1748
EI 1879-0240
J9 INSECT BIOCHEM MOLEC
JI Insect Biochem. Mol. Biol.
PD JAN
PY 2014
VL 44
BP 23
EP 32
DI 10.1016/j.ibmb.2013.10.006
PG 10
WC Biochemistry & Molecular Biology; Entomology
SC Biochemistry & Molecular Biology; Entomology
GA 290QB
UT WOS:000329772300003
ER
PT J
AU Inge, TH
Zeller, MH
Jenkins, TM
Helmrath, M
Brandt, ML
Michalsky, MP
Harmon, CM
Courcoulas, A
Horlick, M
Xanthakos, SA
Dolan, L
Mitsnefes, M
Barnett, SJ
Buncher, R
AF Inge, Thomas H.
Zeller, Meg H.
Jenkins, Todd M.
Helmrath, Michael
Brandt, Mary L.
Michalsky, Marc P.
Harmon, Carroll M.
Courcoulas, Anita
Horlick, Mary
Xanthakos, Stavra A.
Dolan, Larry
Mitsnefes, Mark
Barnett, Sean J.
Buncher, Ralph
CA Teen-LABS Consortium
TI Perioperative Outcomes of Adolescents Undergoing Bariatric Surgery The
Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) Study
SO JAMA PEDIATRICS
LA English
DT Article
ID SEVERELY OBESE ADOLESCENTS; ACADEMIC MEDICAL-CENTERS; DISEASE
RISK-FACTORS; NATIONAL TRENDS; PREVALENCE; CHILDREN; SAFETY; COHORT
AB IMPORTANCE Severe obesity in childhood is a major health problem with few effective treatments. Weight-loss surgery (WLS) is being used to treat severely obese adolescents, although with very limited data regarding surgical safety for currently used, minimally invasive procedures.
OBJECTIVE To assess the preoperative clinical characteristics and perioperative safety outcomes of severely obese adolescents undergoing WLS.
DESIGN, SETTING, AND PARTICIPANTS This prospective, multisite observational study enrolled patients from February 28, 2007, through December 30, 2011. Consecutive patients aged 19 years or younger who were approved to undergo WLS (n = 277) were offered enrollment into the study at 5 academic referral centers in the United States; 13 declined participation and 22 did not undergo surgery after enrollment, thus the final analysis cohort consisted of 242 individuals. There were no withdrawals.
MAIN OUTCOMES AND MEASURES This analysis examined preoperative anthropometrics, comorbid conditions, and major and minor complications occurring within 30 days of operation. All data were collected in a standardized fashion. Reoperations and hospital readmissions were adjudicated by independent reviewers to assess relatedness to the WLS procedure.
RESULTS The mean (SD) age of participants was 17.1 (1.6) years and the median body mass index (calculated as weight in kilograms divided by height in meters squared) was 50.5. Fifty-one percent demonstrated 4 or more major comorbid conditions. Laparoscopic Roux-en-Y gastric bypass, vertical sleeve gastrectomy, and adjustable gastric banding were performed in 66%, 28%, and 6% of patients, respectively. There were no deaths during the initial hospitalization or within 30 days of operation; major complications (eg, reoperation) were seen in 19 patients (8%). Minor complications (eg, readmission for dehydration) were noted in 36 patients (15%). All reoperations and 85% of readmissions were related to WLS.
CONCLUSIONS AND RELEVANCE In this series, adolescents with severe obesity presented with abundant comorbid conditions. We observed a favorable short-term complication profile, supporting the early postoperative safety of WLS in select adolescents. Further longitudinal study of this cohort will permit accurate assessment of long-term outcomes for adolescents undergoing bariatric surgery.
C1 [Inge, Thomas H.; Zeller, Meg H.; Jenkins, Todd M.; Helmrath, Michael; Xanthakos, Stavra A.; Dolan, Larry; Mitsnefes, Mark; Barnett, Sean J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Brandt, Mary L.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Michalsky, Marc P.] Nationwide Childrens Hosp, Columbus, OH USA.
[Harmon, Carroll M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Courcoulas, Anita] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Horlick, Mary] NIDDK, NIH, Bethesda, MD 20892 USA.
[Buncher, Ralph] Univ Cincinnati, Cincinnati, OH USA.
RP Inge, TH (reprint author), Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
RI Michalsky, Marc/E-3674-2011;
OI michalsky, marc/0000-0002-7119-3634
FU National Institute of Diabetes and Digestive and Kidney Diseases
(Cincinnati Children's Hospital Medical Center) [U01DK072493,
UM1DK072493]; National Institute of Diabetes and Digestive and Kidney
Diseases (University of Cincinnati) [UM1DK095710]; National Institutes
of Health (Cincinnati Children's Hospital Medical Center) [UL1
TR000077-04]; National Institutes of Health (Nationwide Children's
Hospital) [UL1RR025755]; National Institutes of Health (Texas Children's
Hospital/Baylor College of Medicine) [M01-RR00188]; National Institutes
of Health (University of Pittsburgh) [UL1 RR024153, UL1TR000005];
National Institutes of Health (University of Alabama, Birmingham) [UL1
TR000165]
FX The Teen-LABS Consortium was funded by cooperative agreements with the
National Institute of Diabetes and Digestive and Kidney Diseases through
grants U01DK072493 (Cincinnati Children's Hospital Medical Center),
UM1DK072493 (Cincinnati Children's Hospital Medical Center), and
UM1DK095710 (University of Cincinnati). The study was also supported by
National Institutes of Health grants UL1 TR000077-04 (Cincinnati
Children's Hospital Medical Center), UL1RR025755 (Nationwide Children's
Hospital), M01-RR00188 (Texas Children's Hospital/Baylor College of
Medicine), UL1 RR024153 and UL1TR000005 (University of Pittsburgh), and
UL1 TR000165 (University of Alabama, Birmingham).
NR 28
TC 64
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U1 1
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JAN
PY 2014
VL 168
IS 1
BP 47
EP 53
DI 10.1001/jamapediatrics.2013.4296
PG 7
WC Pediatrics
SC Pediatrics
GA 291RK
UT WOS:000329846600012
PM 24189578
ER
PT J
AU Chiles, NS
Phillips, CL
Volpato, S
Bandinelli, S
Ferrucci, L
Guralnik, JM
Patel, KV
AF Chiles, Nancy S.
Phillips, Caroline L.
Volpato, Stefano
Bandinelli, Stefania
Ferrucci, Luigi
Guralnik, Jack M.
Patel, Kushang V.
TI Diabetes, peripheral neuropathy, and lower-extremity function
SO JOURNAL OF DIABETES AND ITS COMPLICATIONS
LA English
DT Article
DE Gerontology; Geriatrics; Peripheral neuropathy; Lower extremity function
ID PHYSICAL PERFORMANCE; BODY-COMPOSITION; WOMENS HEALTH; NERVE
DYSFUNCTION; OLDER-ADULTS; AGE; DISABILITY; DECLINE; COMPLICATIONS;
EPIDEMIOLOGY
AB Objective: Diabetes among older adults causes many complications, including decreased lower-extremity function and physical disability. Diabetes can cause peripheral nerve dysfunction, which might be one pathway through which diabetes leads to decreased physical function. The study aims were to determine the following: (1) whether diabetes and impaired fasting glucose are associated with objective measures of physical function in older adults, (2) which peripheral nerve function (PNF) tests are associated with diabetes, and (3) whether PNF mediates the diabetes-physical function relationship.
Research Design and Methods: This study included 983 participants, age 65 years and older from the InCHIANTI study. Diabetes was diagnosed by clinical guidelines. Physical performance was assessed using the Short Physical Performance Battery (SPPB), scored from 0 to 12 (higher values, better physical function) and usual walking speed (m/s). PNF was assessed via standard surface electroneurographic study of right peroneal nerve conduction velocity, vibration and touch sensitivity. Clinical cutpoints of PNF tests were used to create a neuropathy score from 0 to 5 (higher values, greater neuropathy). Multiple linear regression models were used to test associations.
Results and Conclusion: One hundred twenty-six (12.8%) participants had diabetes. Adjusting for age, sex, education, and other confounders, diabetic participants had decreased SPPB (beta = -0.99; p < 0.01), decreased walking speed (beta = -0.1 m/s; p < 0.01), decreased nerve conduction velocity (beta = -1.7 m/s; p < 0.01), and increased neuropathy (beta = 0.25; p < 0.01) compared to non-diabetic participants. Adjusting for nerve conduction velocity and neuropathy score decreased the effect of diabetes on SPPB by 20%, suggesting partial mediation through decreased PNF. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Chiles, Nancy S.] Univ Maryland, Doctoral Program Gerontol, Baltimore, MD 21201 USA.
[Chiles, Nancy S.] Univ Maryland Baltimore Cty, Doctoral Program Gerontol, Baltimore, MD 21201 USA.
[Chiles, Nancy S.; Guralnik, Jack M.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Phillips, Caroline L.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Volpato, Stefano] Univ Ferrara, Dept Med Sci, I-44100 Ferrara, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Patel, Kushang V.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
RP Chiles, NS (reprint author), 660 W Redwood St,Suite 200, Baltimore, MD 21201 USA.
EM nchiles@epiumaryland.edu
RI VOLPATO, STEFANO/H-2977-2014
OI VOLPATO, STEFANO/0000-0003-4335-6034
FU Italian Ministry of Health [ICS 110.1\RS97.71]; Intramural Research
Program of the National Institute on Aging, NIH [N01-AG-916413,
N01-AG-821336, N01-AG-5-0002]
FX The InCHIANTI study was supported as a targeted project (ICS
110.1\RS97.71) by the Italian Ministry of Health and, in part, by the
Intramural Research Program of the National Institute on Aging, NIH
(Contracts N01-AG-916413, N01-AG-821336, and N01-AG-5-0002).
NR 25
TC 16
Z9 16
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1056-8727
EI 1873-460X
J9 J DIABETES COMPLICAT
JI J. Diabetes Complications
PD JAN-FEB
PY 2014
VL 28
IS 1
BP 91
EP 95
DI 10.1016/j.jdiacomp.2013.08.007
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 288DL
UT WOS:000329592100019
PM 24120281
ER
PT J
AU Pecoraro, A
Ewen, E
Horton, T
Mooney, R
Kolm, P
McGraw, P
Woody, G
AF Pecoraro, Anna
Ewen, Edward
Horton, Terry
Mooney, Ruth
Kolm, Paul
McGraw, Patty
Woody, George
TI Using the AUDIT-PC to Predict Alcohol Withdrawal in Hospitalized
Patients
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE alcoholism; addictive behavior; screening; risk assessment; hospital
medicine
ID DISORDERS IDENTIFICATION TEST; OPERATING CHARACTERISTIC CURVES;
PRIMARY-CARE; ROC ANALYSIS; CONSUMPTION; DETOXIFICATION; POPULATION;
PRINCIPLES; SCIENCE; TESTS
AB Alcohol withdrawal syndrome (AWS) occurs when alcohol-dependent individuals abruptly reduce or stop drinking. Hospitalized alcohol-dependent patients are at risk. Hospitals need a validated screening tool to assess withdrawal risk, but no validated tools are currently available.
To examine the admission Alcohol Use Disorders Identification Test-(Piccinelli) Consumption (AUDIT-PC) ability to predict the subsequent development of AWS among hospitalized medical-surgical patients admitted to a non-intensive care setting.
Retrospective case-control study of patients discharged from the hospital with a diagnosis of AWS. All patients with AWS were classified as presenting with AWS or developing AWS later during admission. Patients admitted to an intensive care setting and those missing AUDIT-PC scores were excluded from analysis. A hierarchical (by hospital unit) logistic regression was performed and receiver-operating characteristics were examined on those developing AWS after admission and randomly selected controls. Because those diagnosing AWS were not blinded to the AUDIT-PC scores, a sensitivity analysis was performed.
The study cohort included all patients age a parts per thousand yen18 years admitted to any medical or surgical units in a single health care system from 6 October 2009 to 7 October 2010.
After exclusions, 414 patients were identified with AWS. The 223 (53.9 %) who developed AWS after admission were compared to 466 randomly selected controls without AWS. An AUDIT-PC score a parts per thousand yen4 at admission provides 91.0 % sensitivity and 89.7 % specificity (AUC = 0.95; 95 % CI, 0.94-0.97) for AWS, and maximizes the correct classification while resulting in 17 false positives for every true positive identified. Performance remained excellent on sensitivity analysis (AUC = 0.92; 95 % CI, 0.90-0.93). Increasing AUDIT-PC scores were associated with an increased risk of AWS (OR = 1.68, 95 % CI 1.55-1.82, p < 0.001).
The admission AUDIT-PC score is an excellent discriminator of AWS and could be an important component of future clinical prediction rules. Calibration and further validation on a large prospective cohort is indicated.
C1 [Pecoraro, Anna; Woody, George] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Pecoraro, Anna; Horton, Terry; Woody, George] Delaware Valley Node, NIDA Clin Trials Network, Philadelphia, PA USA.
[Ewen, Edward; Horton, Terry; McGraw, Patty] Christiana Care Hlth Syst, Dept Med, Newark, DE 19718 USA.
[Mooney, Ruth] Christiana Care Hlth Syst, Dept Nursing, Newark, DE 19718 USA.
[Kolm, Paul] Christiana Care Hlth Syst, Ctr Outcomes Res, Newark, DE 19718 USA.
RP Ewen, E (reprint author), Christiana Care Hlth Syst, John H Ammon Med Educ Ctr, Dept Med, Suite 2E70, Newark, DE 19718 USA.
EM eewen@christianacare.org
RI Ewen, Edward/O-1904-2013
OI Ewen, Edward/0000-0003-4838-8182
FU National Institute on Drug Abuse (NIDA): Clinical Trials Network (CTN)
[U10 DA-13043, KO5 DA-17009]
FX This work was not funded by any external sources. Drs. Pecoraro and
Woody receive salary support through the National Institute on Drug
Abuse (NIDA): Clinical Trials Network (CTN) U10 DA-13043 (Pecoraro and
Woody) and KO5 DA-17009 (Woody).
NR 29
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U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JAN
PY 2014
VL 29
IS 1
BP 34
EP 40
DI 10.1007/s11606-013-2551-9
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 284WR
UT WOS:000329352900014
PM 23959745
ER
PT J
AU Danis, M
Sommers, R
Logan, J
Weidmer, B
Chen, S
Goold, S
Pearson, S
McGlynn, E
AF Danis, Marion
Sommers, Roseanna
Logan, Jean
Weidmer, Beverly
Chen, Shirley
Goold, Susan
Pearson, Steven
McGlynn, Elizabeth
TI Exploring Public Attitudes Towards Approaches to Discussing Costs in the
Clinical Encounter
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE communication; decision making; health care costs; patient engagement
ID OUT-OF-POCKET; EMPATHIC COMMUNICATION; CARE; BARRIERS; SEEKING; END
AB Patients' willingness to discuss costs of treatment alternatives with their physicians is uncertain.
To explore public attitudes toward doctor-patient discussions of insurer and out-of-pocket costs and to examine whether several possible communication strategies might enhance patient receptivity to discussing costs with their physicians.
Focus group discussions and pre-discussion and post-discussion questionnaires.
Two hundred and eleven insured individuals with mean age of 48 years, 51 % female, 34 % African American, 27 % Latino, and 50 % with incomes below 300 % of the federal poverty threshold, participated in 22 focus groups in Santa Monica, CA and in the Washington, DC metro area.
Attitudes toward discussing out-of-pocket and insurer costs with physicians, and towards physicians' role in controlling costs; receptivity toward recommended communication strategies regarding costs.
Participants expressed more willingness to talk to doctors about personal costs than insurer costs. Older participants and sicker participants were more willing to talk to the doctor about all costs than younger and healthier participants (OR = 1.8, p = 0.004; OR = 1.6, p = 0.027 respectively). Participants who face cost-related barriers to accessing health care were in greater agreement than others that doctors should play a role in reducing out-of-pocket costs (OR = 2.4, p = 0.011). Participants did not endorse recommended communication strategies for discussing costs in the clinical encounter. In contrast, participants stated that trust in one's physician would enhance their willingness to discuss costs. Perceived impediments to discussing costs included rushed, impersonal visits, and clinicians who are insufficiently informed about costs.
This study suggests that trusting relationships may be more conducive than any particular discussion strategy to facilitating doctor-patient discussions of health care costs. Better public understanding of how medical decisions affect insurer costs and how such costs ultimately affect patients personally will be necessary if discussions about insurer costs are to occur in the clinical encounter.
C1 [Danis, Marion; Sommers, Roseanna; Logan, Jean; Pearson, Steven] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Weidmer, Beverly] RAND Corp, Santa Monica, CA USA.
[Chen, Shirley; Goold, Susan] Univ Michigan, Ann Arbor, MI 48109 USA.
[McGlynn, Elizabeth] Kaiser Permanente, Oakland, CA USA.
RP Danis, M (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA.
EM mdanis@nih.gov
OI Goold, Susan Dorr/0000-0002-0258-9774
FU Intramural Research Program of the NIH, The Office of the Director of
the NIH; Department of Bioethics at the NIH Clinical Center
FX This research was supported by the Intramural Research Program of the
NIH, The Office of the Director of the NIH and the Department of
Bioethics at the NIH Clinical Center.
NR 28
TC 13
Z9 13
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JAN
PY 2014
VL 29
IS 1
BP 223
EP 229
DI 10.1007/s11606-013-2543-9
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 284WR
UT WOS:000329352900048
PM 23881272
ER
PT J
AU Lehmann, T
Dao, A
Yaro, AS
Diallo, M
Timbine, S
Huestis, DL
Adamou, A
Kassogue, Y
Traore, AI
AF Lehmann, Tovi
Dao, A.
Yaro, A. S.
Diallo, M.
Timbine, S.
Huestis, D. L.
Adamou, A.
Kassogue, Y.
Traore, A. I.
TI Seasonal Variation in Spatial Distributions of Anopheles gambiae in a
Sahelian Village: Evidence for Aestivation
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE spatial aggregation; dry-season diapause; hotspot; malaria;
long-distance migration
ID WESTERN KENYA HIGHLANDS; MALARIA TRANSMISSION; DRY SEASON;
MOLECULAR-FORMS; VECTOR CONTROL; METABOLIC-RATE; SUDAN SAVANNA;
HIGH-ALTITUDE; S FORMS; COMPLEX
AB Changes in spatial distribution of mosquitoes over time in a Sahelian village were studied to understand the sources of the mosquitoes during the dry season when no larval sites are found. At that time, the sources of Anopheles gambiae Giles may be local shelters used by aestivating mosquitoes or migrants from distant populations. The mosquito distribution was more aggregated during the dry season, when few houses had densities 7- to 24-fold higher than expected. The high-density houses during the dry season differed from those of the wet season. Most high-density houses during the dry season changed between years, yet their vicinity was rather stable. Scan statistics confirmed the presence of one or two adjacent hotspots in the dry season, usually found on one edge of the village. These hotspots shifted between the early and late dry season. During the wet season, the hotspots were relatively stable near the main larval site. The locations of the hotspots in the wet season and early and late dry season were similar between years. Season-specific, stable, and focal hotspots are inconsistent with the predictions based on the arrival of migrants from distant localities during the dry season, but are consistent with the predictions based on local shelters used by aestivating mosquitoes. Targeting hotspots in Sahelian villages for vector control may not be effective because the degree of aggregation is moderate, the hotspots are not easily predicted, and they are not the sources of the population. However, targeting the dry-season shelters may be highly cost-effective, once they can be identified and predicted.
C1 [Lehmann, Tovi; Huestis, D. L.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Dao, A.; Yaro, A. S.; Diallo, M.; Timbine, S.; Adamou, A.; Kassogue, Y.; Traore, A. I.] Univ Sci Tech & Technol, Mali Int Ctr Excellence Res ICER, Bamako, Mali.
RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM tlehmann@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank the villagers in Thierola for their hospitality and assistance
with mosquito collections; Dia Elnaiem, Jose Ribeiro, Nafo Sogoba,
Zhijian (Jake) Tu, and Mike Levy for their helpful comments on previous
versions of this manuscript; and Cheick Traore, Richard Sakai, Robert
Gwadz, and Thomas Wellems for logistical support. This study was
supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health.
NR 53
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Z9 8
U1 2
U2 11
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
EI 1938-2928
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD JAN
PY 2014
VL 51
IS 1
BP 27
EP 38
DI 10.1603/ME13094
PG 12
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 291CF
UT WOS:000329804600003
PM 24605449
ER
PT J
AU Sandoz, KM
Sturdevant, DE
Hansen, B
Heinzen, RA
AF Sandoz, Kelsi M.
Sturdevant, Daniel E.
Hansen, Bryan
Heinzen, Robert A.
TI Developmental transitions of Coxiella bumetii grown in axenic media
SO JOURNAL OF MICROBIOLOGICAL METHODS
LA English
DT Article
DE Q fever; Coxiella; Differentiation; Axenic growth; Development;
Viability
ID Q-FEVER; LEGIONELLA-PNEUMOPHILA; BORDETELLA-PERTUSSIS;
HYDROGEN-PEROXIDE; FATTY-ACIDS; BURNETII; CYCLODEXTRINS; CYCLE;
BACTERIA; ENZYMES
AB Coxiella burnetii undergoes a biphasic developmental cycle within its host cell that generates morphologically and physiologically distinct large cell variants (LCV) and small cell variants (SCV). During the lag phase of the C. burnetii growth cycle, non-replicating SCV differentiate into replicating LCV that in turn differentiate back into SCV during stationary phase. Nearly homogeneous SCV are observed in infected Vero cells after extended incubation (21 to 28 days). In the current study, we sought to establish whether C burnetii developmental transitions in host cells are recapitulated during host cell-free (axenic) growth in first and second generation acidified citrate cysteine media (ACCM-1 and ACCM-2, respectively). We show that ACCM-2 supported developmental transitions and viability. Although ACCM-1 also supported SCV to LCV transition, LCV to SCV transition did not occur after extended incubation (21 days). Instead, C burnetii exhibited a ghost-like appearance with bacteria containing condensed chromatin but otherwise devoid of cytoplasmic content. This phenotype correlated with a near total loss in viability between 14 and 21 days of cultivation. Transcriptional profiling of C burnetii following 14 days of incubation revealed elevated expression of oxidative stress genes in ACCM-1 cultivated bacteria. ACCM-2 differs from ACCM-1 by the substitution of methyl-beta-cyclodextrin (M beta-CD) for fetal bovine serum. Addition of M beta-CD to ACCM-1 at 7 days post-inoculation rescued C burnetii viability and lowered expression of oxidative stress genes. Thus, M beta-CD appears to alleviate oxidative stress in ACCM-2 to result in C burnetii developmental transitions and viability that mimic host cell-cultivated organisms. Axenic cultivation of C burnetii in ACCM-2 and new methods of genetic manipulation now allow investigation of the molecular basis of C burnetii biphasic development. Published by Elsevier B.V.
C1 [Sandoz, Kelsi M.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Lab Intracellular Parasites, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Sturdevant, Daniel E.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Hansen, Bryan] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Heinzen, RA (reprint author), Rocky Mt Labs, 903 South 4th St, Hamilton, MT 59840 USA.
EM rheinzen@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX We thank Anders Omsland for critical review of the manuscript. This work
was supported by the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases.
NR 38
TC 6
Z9 8
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7012
EI 1872-8359
J9 J MICROBIOL METH
JI J. Microbiol. Methods
PD JAN
PY 2014
VL 96
BP 104
EP 110
DI 10.1016/j.mimet.2013.11.010
PG 7
WC Biochemical Research Methods; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 290PO
UT WOS:000329771000020
PM 24286928
ER
PT J
AU Steffen-Smith, EA
Baker, EH
Venzon, D
Shandilya, S
Bent, RS
Warren, KE
AF Steffen-Smith, Emilie A.
Baker, Eva H.
Venzon, David
Shandilya, Shaefali
Bent, Robyn S.
Warren, Katherine E.
TI Measurements of the pons as a biomarker of progression for pediatric
DIPG
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Pediatric brain tumors; Diffuse intrinsic pontine glioma; Magnetic
resonance imaging; Measurements; Prognosis
ID INTRINSIC PONTINE GLIOMAS; BRAIN-STEM GLIOMAS; CLINICAL-TRIALS; DIFFUSE;
CHILDREN; MRI; SPECTROSCOPY; SURVIVAL
AB Treatment of pediatric diffuse intrinsic pontine glioma (DIPG) remains challenging, and reliable biomarkers of response are lacking. Radiographic response is a primary endpoint in many investigational studies of brain tumors, but there is no standard method of tumor measurement for DIPG, significant inter-observer variability exists given the invasive nature of these tumors, and tumor measurements are not predictive of outcome. Because DIPGs involve a significant portion of the pons, we evaluated the reliability and prognostic value of one-dimensional (1D) and two-dimensional (2D) pons measurements using anatomical landmarks rather than tumor boundaries. Patients with DIPG (n = 75) were evaluated longitudinally at our institution using MRI. Four readers independently performed 1D and 2D measurements of the pons using FLAIR images. Agreement and inter-reader variability were evaluated using differences among the six reader pairs and the coefficient of variation (CV). Prognostic value of pons measurements was calculated using Cox proportional hazards models, where relative hazard (RH) represents risk of death. Readers evaluated 384 exams. Agreement of readers' 1D and 2D measurements was strong (median difference between reader pairs 3.1 and 5.4 %, respectively), with low inter-reader variability (median CV = 3.1 % and median CV = 4.8 %, respectively). Increases in 1D and 2D pons measurements over time indicated poorer prognosis (RH = 2.29, p = 0.0025 and RH = 1.13, p = 0.0016, respectively), with shorter overall survival. Pons measurements had low inter-reader variability compared to previously reported tumor measurement techniques and correlated with outcome in children with DIPG. Measurements of the pons (as opposed to direct measurements of tumor) are a viable in vivo biomarker for DIPG.
C1 [Steffen-Smith, Emilie A.; Shandilya, Shaefali; Bent, Robyn S.; Warren, Katherine E.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
RP Steffen-Smith, EA (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10 Room 1-5750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM steffene@mail.nih.gov; warrenk@mail.nih.gov
OI Steffen-Smith, Emilie/0000-0002-4966-3046
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was presented in part at the 2012 International Society of
Pediatric Neuro-Oncology meeting in Toronto, Ontario Canada. This
research was supported in part by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The views expressed do not necessarily represent the
views of the National Institutes of Health or the United States
Government.
NR 21
TC 3
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JAN
PY 2014
VL 116
IS 1
BP 127
EP 133
DI 10.1007/s11060-013-1266-4
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 288OU
UT WOS:000329622100016
PM 24113877
ER
PT J
AU Nash, SH
Kristal, AR
Hopkins, SE
Boyer, BB
O'Brien, DM
AF Nash, Sarah H.
Kristal, Alan R.
Hopkins, Scarlett E.
Boyer, Bert B.
O'Brien, Diane M.
TI Stable Isotope Models of Sugar Intake Using Hair, Red Blood Cells, and
Plasma, but Not Fasting Plasma Glucose, Predict Sugar Intake in a Yup'ik
Study Population
SO JOURNAL OF NUTRITION
LA English
DT Article
ID SWEETENED BEVERAGE INTAKE; ASSESSING DIETARY-INTAKE; LIFE-SPAN; C-13
ABUNDANCE; CARBON; DELTA-C-13; BIOMARKER; NITROGEN; DELTA-N-15; FRUCTOSE
AB Objectively measured biomarkers will help to resolve the controversial role of sugar intake in the etiology of obesity and related chronic diseases. We recently validated a dual-isotope model based on RBC carbon (delta C-13) and nitrogen (delta N-15) isotope ratios that explained a large percentage of the variation in self-reported sugar intake in a Yup'ik study population..Stable isotope ratios can easily be measured from many tissues, including RBCs, plasma, and hair; however, it is not known how isotopic models of sugar intake compare among these tissues. Here, we compared self-reported sugar intake with models based on RBCs, plasma, and hair delta C-13 and delta N-15 in Yup'ik people. We also evaluated associations of sugar intake with fasting plasma glucose delta C-13. Finally, we evaluated relations between delta C-13 and delta N-15 values in hair, plasma, RBCs, and fasting plasma glucose to allow comparison of isotope ratios across tissue types. Models using RBCs, plasma, or hair isotope ratios explained similar amounts of variance in total sugar, added sugar, and sugar-sweetened beverage intake (similar to 53%, 48%, and 34%, respectively); however, the association with delta C-13 was strongest for models based on RBCs and hair. There were no associations with fasting plasma glucose delta C-13 (R-2 = 0.03). The delta C-13 and delta N-15 values of RBCs, plasma, and hair showed strong, positive correlations; the slopes of these relations did not differ from 1. This study demonstrates that RBC, plasma, and hair isotope ratios predict sugar intake and provides data that will allow comparison of studies using different sample types.
C1 [Nash, Sarah H.; Hopkins, Scarlett E.; Boyer, Bert B.; O'Brien, Diane M.] Univ Alaska Fairbanks, Inst Arctic Biol, Ctr Alaska Native Hlth Res, Fairbanks, AK USA.
[Nash, Sarah H.; Boyer, Bert B.; O'Brien, Diane M.] Univ Alaska Fairbanks, Dept Biol & Wildlife, Fairbanks, AK USA.
[Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Nash, SH (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
EM sarahhnash@gmail.com
RI O'Brien, Diane/B-2919-2010;
OI O'Brien, Diane/0000-0001-5807-9661; Kristal, Alan/0000-0002-7329-1617
FU National Center for Research Resources; National Institute of General
Medical Sciences of the NIH [P20RR016430]; NIH National Institute of
Diabetes and Digestive and Kidney Diseases [R01DK07442]
FX Supported by the National Center for Research Resources and the National
Institute of General Medical Sciences of the NIH through grant no.
P20RR016430 and NIH National Institute of Diabetes and Digestive and
Kidney Diseases through grant no. R01DK07442. The contents of this
article are solely the responsibility of the authors and do not
necessarily represent the official views of the National Center for
Research Resources or the NIH.
NR 30
TC 6
Z9 6
U1 0
U2 8
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JAN
PY 2014
VL 144
IS 1
BP 75
EP 80
DI 10.3945/jn.113.182113
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 287GU
UT WOS:000329530800013
PM 24198311
ER
PT J
AU Ravillah, D
Mohammed, A
Qian, L
Brewer, M
Zhang, YT
Biddick, L
Steele, VE
Rao, CV
AF Ravillah, Durgadevi
Mohammed, Altaf
Qian, Li
Brewer, Misty
Zhang, Yuting
Biddick, Laura
Steele, Vernon E.
Rao, Chinthalapally V.
TI Chemopreventive Effects of an HDAC2-Selective Inhibitor on Rat Colon
Carcinogenesis and APC(min/+) Mouse Intestinal Tumorigenesis
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID;
COLORECTAL-CANCER; CELL-CYCLE; PHASE-I; CHROMATIN-STRUCTURE;
MOLECULAR-ORIGINS; HDAC2 EXPRESSION; APC GENE; APOPTOSIS
AB Epigenetic modulators, particularly histone deacetylases (HDACs), are valid targets for cancer prevention and therapy. Recent studies report that HDAC2 overexpression is associated with colon tumor progression and is a potential target for colon cancer prevention. This study tested chemopreventive and dose-response effects of Ohio State University HDAC42 (OSU-HDAC42), a selective HDAC2 inhibitor, using a rat colon carcinogenesis model to assess aberrant crypt foci inhibition and a familial adenomatous polyposis model to assess intestinal tumor inhibition. Colonic aberrant crypt foci were induced by azoxymethane (AOM) (15 mg/kg body weight, once-weekly subcutaneous injections at 8 and 9 weeks age). One week after AOM treatment, groups of rats were fed an AIN-76A diet containing 0, 75, 150, and 300 ppm OSU-HDAC42 for 8 weeks, and colonic aberrant crypt foci were evaluated. To assess the inhibitory effect of OSU-HDAC42 on small-intestinal polyps and colon tumor growth, 6-week-old male C57Bl/6J-APC(min/+)mice were fed an AIN-76A diet containing 150 ppm OSU-HADC42 or 300 ppm pan-HDAC inhibitor suberoylanilide hydroxyamic acid (SAHA) for 80 days. Our results demonstrate that dietary OSU-HDAC42 produced dose-dependent inhibition of AOM-induced colonic aberrant crypt foci formation (13-50%; P, 0.01 to, 0.0001) and reduced multiple crypts with >= 4 crypts per focus (25-57%; P, 0.01 to, 0.0001) in F344 rats. Our findings show that 150 ppm OSU-HDAC42 significantly inhibited small-intestinal polyps (. 46%; P, 0.001), with polyp size measuring.1 mm (P, 0.001), and colon tumors (. 26%) in APCmin/1mice, whereas 300 ppm SAHA showed nonsignificant inhibition. Mice fed 150 ppm OSU-HDAC42 had significantly decreased HDAC2, proliferating cell nuclear antigen, B cell lymphoma 2, cyclin-dependent kinase 2, and cell division cycle homolog 25C expression levels and increased p53 expression levels. These observations demonstrate the chemopreventive efficacy of OSU-HDAC42 against chemically induced and polyposis models of intestinal tumorigenesis.
C1 [Ravillah, Durgadevi; Mohammed, Altaf; Qian, Li; Brewer, Misty; Zhang, Yuting; Biddick, Laura; Rao, Chinthalapally V.] Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, Hematol Oncol Sect,Dept Med,PCS Oklahoma Canc Ctr, Oklahoma City, OK 73104 USA.
[Steele, Vernon E.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, NIH, Bethesda, MD 20892 USA.
RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, 975 NE 10th St,BRC Bldg 2,Room 1203, Oklahoma City, OK 73104 USA.
EM cv-rao@ouhsc.edu
FU NCI NIH HHS [N01CN53300, N01-CN53300]
NR 49
TC 4
Z9 5
U1 0
U2 0
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JAN
PY 2014
VL 348
IS 1
BP 59
EP 68
DI 10.1124/jpet.113.208645
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 292OI
UT WOS:000329911200006
PM 24218540
ER
PT J
AU Desai, RI
Grandy, DK
Lupica, CR
Katz, JL
AF Desai, Rajeev I.
Grandy, David K.
Lupica, Carl R.
Katz, Jonathan L.
TI Pharmacological Characterization of a Dopamine Transporter Ligand That
Functions as a Cocaine Antagonist
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID UPTAKE INHIBITORS; IN-VIVO; BENZTROPINE ANALOGS;
3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; H-3 WIN-35,428; RATS; RECEPTOR;
BINDING; DRUGS; MICE
AB An N-butyl analog of benztropine, JHW007 [N-(n-butyl)-3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane], binds to dopamine transporters (DAT) but has reduced cocaine-like behavioral effects and antagonizes various effects of cocaine. The present study further examined mechanisms underlying these effects. Cocaine dose-dependently increased locomotion, whereas JHW007 was minimally effective but increased activity 24 hours after injection. JHW007 (3-10 mg/kg) dose-dependently and fully antagonized the locomotor-stimulant effects of cocaine (5-60 mg/kg), whereas N-methyl and N-allyl analogs and the dopamine (DA) uptake inhibitor GBR12909 [1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride] stimulated activity and failed to antagonize effects of cocaine. JHW007 also blocked the locomotor-stimulant effects of the DAT inhibitor GBR12909 but not stimulation produced by the delta-opioid agonist SNC 80 [4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazin-1-yl](3-methoxyphenyl)methyl]-N,N-diethylbenzamide], which increases activity through nondopaminergic mechanisms. JHW007 blocked locomotor-stimulant effects of cocaine in both DA D2- and CB1-receptor knockout and wild-type mice, indicating a lack of involvement of these targets. Furthermore, JHW007 blocked effects of cocaine on stereotyped rearing but enhanced stereotyped sniffing, suggesting that interference with locomotion by enhanced stereotypies is not responsible for the cocaine-antagonist effects of JHW007. Time-course data indicate that administration of JHW007 antagonized the locomotor-stimulant effects of cocaine within 10 minutes of injection, whereas occupancy at the DAT, as determined in vivo, did not reach a maximum until 4.5 hours after injection. The sigma(1)-receptor antagonist BD 1008 [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine dihydrobromide] blocked the locomotor-stimulant effects of cocaine. Overall, these findings suggest that JHW007 has cocaine-antagonist effects that are deviate from its DAT occupancy and that some other mechanism, possibly sigma-receptor antagonist activity, may contribute to the cocaineantagonist effect of JHW007 and like drugs.
C1 [Desai, Rajeev I.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Grandy, David K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM jkatz@intra.nida.nih.gov
OI Katz, Jonathan/0000-0002-1068-1159
FU Intramural Research Program of the National Institutes of Health
[National Institute on Drug Abuse]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health [National Institute on Drug Abuse].
NR 33
TC 5
Z9 7
U1 1
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JAN
PY 2014
VL 348
IS 1
BP 106
EP 115
DI 10.1124/jpet.113.208538
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 292OI
UT WOS:000329911200011
PM 24194528
ER
PT J
AU Gotoh, S
Negishi, M
AF Gotoh, Saki
Negishi, Masahiko
TI Serum- and Glucocorticoid-Regulated Kinase 2 Determines Drug-Activated
Pregnane X Receptor to Induce Gluconeogenesis in Human Liver Cells
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID CROSS-TALK; PROTEIN-KINASE; GLUCOSE; RIFAMPIN; MOUSE; PHARMACODYNAMICS;
PHARMACOKINETICS; METABOLISM; TRANSPORT; AGONISTS
AB Drug activation of the human nuclear pregnane X receptor (PXR) induced gluconeogenic genes and increased glucose production. In this study, we have determined that serum-and glucocorticoid-regulated kinase 2 (SGK2) is an essential factor that mediates this PXR-regulated glucose 6-phosphatase (G6Pase) induction and glucose production. Both SGK2 and G6Pase mRNAs were increased in rifampicin-treated HepG2 cells stably expressing human PXR. Reporter and chromatin immunoprecipitation assays delineated PXR activation of the SGK2 gene to a distal and proximal DNA sequence within its promoter: distal PXR response element (-2587/-2209) and proximal PXR response element (-115/-75), respectively. Small interfering RNA (siRNA) knockdown of SGK2 severely attenuated PXR-regulated induction of G6Pase as well as glucose production. SGK2 constitutes an insulin-independent signal pathway to regulate gluconeogenesis because siRNA knockdown of the insulin-responsive transcription factor forkhead box protein O1 did not affect rifampicin induction of G6Pase. Rifampicin treatment of two different samples of human primary hepatocytes revealed that PXR induces G6Pase in the presence of high levels of SGK2, whereas PXR represses G6Pase in its absence. Mediating PXR activation of the G6Pase gene is the first biological role found for hepatic SGK2 and might have therapeutic implications for side effects, such as diabetes, caused by drugs that activate PXR.
C1 [Gotoh, Saki; Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU Intramural Research Program of National Institutes of Health National
Institute of Environmental Health Sciences [Z01ES1005-01]
FX This work was supported by the Intramural Research Program of National
Institutes of Health National Institute of Environmental Health Sciences
[Grant Z01ES1005-01].
NR 22
TC 6
Z9 6
U1 0
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JAN
PY 2014
VL 348
IS 1
BP 131
EP 140
DI 10.1124/jpet.113.209379
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 292OI
UT WOS:000329911200014
PM 24204015
ER
PT J
AU Hiranita, T
Kohut, SJ
Soto, PL
Tanda, G
Kopajtic, TA
Katz, JL
AF Hiranita, Takato
Kohut, Stephen J.
Soto, Paul L.
Tanda, Gianluigi
Kopajtic, Theresa A.
Katz, Jonathan L.
TI Preclinical Efficacy of N-Substituted Benztropine Analogs as Antagonists
of Methamphetamine Self-Administration in Rats
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID DOPAMINE UPTAKE INHIBITORS; RHESUS-MONKEYS; MESOLIMBIC DOPAMINE; BINDING
AFFINITIES; COCAINE DEPENDENCE; RECEPTOR-BINDING; HEROIN ADDICTION;
SIGMA-RECEPTOR; AGONIST-LIKE; JHW 007
AB Atypical dopamine-uptake inhibitors have low abuse potential and may serve as leads for development of cocaine-abuse treatments. Among them, the benztropine (BZT) derivatives, N-butyl (JHW007), N-allyl (AHN2-005), and N-methyl (AHN1-055) analogs of 3 alpha-[bis(4'-fluorophenyl) methoxy]-tropane dose-dependently decreased cocaine self-administration without effects on food-maintained responding. Our study examined selectivity by assessing their effects on self-administration of other drugs. As with cocaine, each BZT analog (1.0-10.0 mg/kg i. p.) dose-dependently decreased maximal self-administration of d-methamphetamine (0.01-0.32 mg/kg/infusion) but was inactive against heroin (1.0-32.0 mu g/kg/infusion) and ketamine (0.032-1.0 mg/kg/infusion) self-administration. Further, standard dopamine indirect-agonists [WIN35,428 ((2)-3 beta-(4-fluorophenyl)- tropan-2-beta-carboxylic acid methyl ester tartrate), damphetamine (0.1-1.0 mg/kg i.p., each)] dose-dependently left-shifted self-administration dose-effect curves for d-methamphetamine, heroin, and ketamine. Noncompetitive NMDAglutamate receptor/channel antagonists [(+)-MK-801 (0.01-0.1 mg/kg i.p.), memantine (1.0-10.0 mg/kg i.p.)] also left-shifted dose-effect curves for d-methamphetamine and ketamine (but not heroin) self-administration. The mu-agonists [dl-methadone and morphine (1.0-10.0 mg/kg i. p., each)] dose-dependently decreased maximal self-administration of m-agonists (heroin, remifentanil) but not d-methamphetamine or ketamine self-administration. The mu-agonist-induced decreases were similar to the effects of BZT analogs on stimulant self-administration and effects of food prefeeding on responding maintained by food reinforcement. Radioligand-binding and behavioral studies suggested that inhibition of dopamine transporters and sigma receptors were critical for blocking stimulant self-administration by BZT-analogs. Thus, the present results suggest that the effects of BZT analogs on stimulant self-administration are similar to effects of mu-agonists on mu-agonist self-administration and food prefeeding on food-reinforced responding, which implicates behavioral mechanisms for these effects and further supports development of atypical dopamine uptake inhibitors as medications for stimulant abuse.
C1 [Hiranita, Takato; Kohut, Stephen J.; Tanda, Gianluigi; Kopajtic, Theresa A.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Soto, Paul L.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Behav Biol, Baltimore, MD 21205 USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM jkatz@intra.nida.nih.gov
RI Tanda, Gianluigi/B-3318-2009;
OI Tanda, Gianluigi/0000-0001-9526-9878; Katz, Jonathan/0000-0002-1068-1159
FU Intramural Research Program of the National Institutes of Health
National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Institute on Drug Abuse.
NR 52
TC 10
Z9 11
U1 1
U2 6
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JAN
PY 2014
VL 348
IS 1
BP 174
EP 191
DI 10.1124/jpet.113.208264
PG 18
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 292OI
UT WOS:000329911200018
PM 24194527
ER
PT J
AU Ganmaa, D
Holick, MF
Rich-Edwards, JW
Frazier, LA
Davaalkham, D
Ninjin, B
Janes, C
Hoover, RN
Troisi, R
AF Ganmaa, Davaasambuu
Holick, Michael F.
Rich-Edwards, Janet W.
Frazier, Lindsay A.
Davaalkham, Dambadarjaa
Ninjin, Boldbaatar
Janes, Craig
Hoover, Robert N.
Troisi, Rebecca
TI Vitamin D deficiency in reproductive age Mongolian women: A cross
sectional study
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE 25-Hydroxyvitamin D; Vitamin D; Vitamin D deficiency; Healthy women;
Reproductive age
ID 25-HYDROXYVITAMIN D CONCENTRATIONS; BODY-MASS INDEX; LIVER-CIRRHOSIS;
BINDING-PROTEIN; D INSUFFICIENCY; D METABOLITES; RISK; PREVALENCE;
PREGNANCY; DISEASE
AB Vitamin D production is critical not only for rickets prevention but for its role in several chronic diseases of adulthood. Maternal vitamin D status also has consequences for the developing fetus.
This study assessed the prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/ml) and insufficiency [25(OH)D = 20-29 ng/ml] in spring, among reproductive age Mongolian women.
Blood was drawn in March and April, 2009 from 420 Mongolian women, 18-44 years of age. Serum 25(OH)D concentrations were measured, anthropometric measurements were performed and information was collected by interview on lifestyle, dietary and reproductive factors. Logarithm-transformed 25(OH)D levels were compared across risk factor categories by analysis of variance. Linear regression analysis was used to assess the independent associations of factors with vitamin D status. Cutaneous vitamin D-3 synthesis was assessed between December and July using a standard 7-dehydrocholesterol ampoule model.
The vast majority of women 415 (98.8%) had serum 25(OH)D < 20 ng/ml (50 nmol/l) with an additional 4 women (<1%) in the insufficient range (20-29 ng/ml); only one women (0.2%) had sufficient levels (>30 ng/ml or 75 nmol/l). 25(OH)D concentrations were positively and independently associated with educational status and use of vitamin D supplements, but not with other demographic, lifestyle, reproductive, or anthropometric factors. 25(OH)D levels were not associated with dietary factors in this population, as there is little access to foods containing vitamin D in Mongolia. No production of previtamin D-3 was observed until March and was maximally effective in April and was sustained through July.
These data suggest that the prevalence of vitamin D deficiency in spring among reproductive age women in Mongolia is high. Given the lack of naturally vitamin D-rich food in the diet and limited use of vitamin D supplements, food fortification and/or supplementation with vitamin D should be considered among these women. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ganmaa, Davaasambuu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Rich-Edwards, Janet W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ganmaa, Davaasambuu] Harvard Univ, Sch Med, Dept Med, Channing Lab, Cambridge, MA 02138 USA.
[Rich-Edwards, Janet W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Connors Ctr Womens Hlth & Gender Biol, Cambridge, MA 02138 USA.
[Holick, Michael F.] Boston Univ, Med Ctr, Dept Med, Boston, MA 02215 USA.
[Holick, Michael F.] Boston Univ, Med Ctr, Dept Physiol & Biophys, Vitamin Skin & Bone Res Lab D, Boston, MA 02215 USA.
[Holick, Michael F.] Boston Univ, Med Ctr, Biol Effects Light Res Ctr, Boston, MA 02215 USA.
[Frazier, Lindsay A.] Dana Farber Childrens Canc Ctr, Dept Pediat Oncol, Boston, MA USA.
[Davaalkham, Dambadarjaa; Ninjin, Boldbaatar] Hlth Sci Univ Mongolia, Ulaanbaatar, Mongol Peo Rep.
[Janes, Craig] Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada.
[Hoover, Robert N.; Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA.
EM gdavaasa@hsph.harvard.edu
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services
FX This research was supported by the National Cancer Institute, National
Institutes of Health, Department of Health and Human Services.
NR 40
TC 7
Z9 7
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD JAN
PY 2014
VL 139
BP 1
EP 6
DI 10.1016/j.jsbmb.2013.09.011
PG 6
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 288GF
UT WOS:000329599300001
PM 24076033
ER
PT J
AU Deye, GA
Magill, AJ
AF Deye, Gregory A.
Magill, Alan J.
TI Primaquine for Prophylaxis of Malaria: Has the CYP Sailed?
SO JOURNAL OF TRAVEL MEDICINE
LA English
DT Editorial Material
ID NONIMMUNE COLOMBIAN SOLDIERS; PLASMODIUM-VIVAX MALARIA;
PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; DOXYCYCLINE; CHLOROQUINE;
FALCIPARUM; MEFLOQUINE; TRAVELERS; 2D6
C1 [Deye, Gregory A.] NIH, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA.
[Magill, Alan J.] Bill & Melinda Gates Fdn, Seattle, WA USA.
RP Deye, GA (reprint author), NIAID, NIH, DMID, 6610 Rockledge Dr, North Bethesda, MD 20817 USA.
EM gregory.deye@nih.gov
NR 14
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1195-1982
EI 1708-8305
J9 J TRAVEL MED
JI J. Travel Med.
PD JAN
PY 2014
VL 21
IS 1
BP 67
EP 69
DI 10.1111/jtm.12080
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 285DC
UT WOS:000329372400014
PM 24251618
ER
PT J
AU Liu, XF
Xiang, LM
FitzGerald, DJ
Pastan, I
AF Liu, Xiu-Fen
Xiang, Laiman
FitzGerald, David J.
Pastan, Ira
TI Antitumor Effects of Immunotoxins Are Enhanced by Lowering HCK or
Treatment with Src Kinase Inhibitors
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID PSEUDOMONAS EXOTOXIN; FAMILY KINASES; MEDIATED APOPTOSIS; PHASE-I;
MESOTHELIOMA; ACTIVATION; LEUKEMIA; GROWTH; TOXIN; CELLS
AB Recombinant immunotoxins (RIT) are agents being developed for cancer treatment. They are composed of an Fv that binds to a cancer cell, fused to a 38-kDa fragment of Pseudomonas exotoxin A. SS1P is a RIT that targets mesothelin, a protein expressed on mesothelioma as well as pancreatic, ovarian, lung, and other cancers. Because the protein tyrosine kinase family regulates a variety of cellular processes and pathways, we hypothesized that tyrosine kinases might regulate susceptibility to immunotoxin killing. To investigate their role, we used siRNAs to lower the level of expression of the 88 known tyrosine kinases. We identified five tyrosine kinases, INSR, HCK, SRC, PDGFR beta, and BMX that enhance the activity of SS1P when their level of expression is lowered by siRNAs. We further investigated the Src family member HCK in this study. Knocking down of SRC slightly increased SS1P killing in A431/H9 cells, but knocking down HCK substantially enhanced killing by SS1P. We investigated the mechanism of enhancement and found that HCK knockdown enhanced SS1P cleavage by furin and lowered levels of Mcl-1 and raised Bax. We then found that Src inhibitors mimic the stimulatory effect of HCK knockdown; both SU6656 and SKI-606 (bosutinib) enhanced immunotoxin killing of mesothelin-expressing cells by SS1P and CD22-expressing cells by HA22 (moxetumomab pasudotox). SU6656 also enhanced the antitumor effects of SS1P and HA22 in mouse xenograft tumor models. Our data suggest that the combination of immunotoxin with tyrosine kinase inhibitors may be an effective way to treat some cancers.
C1 [Liu, Xiu-Fen; Xiang, Laiman; FitzGerald, David J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@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 32
TC 9
Z9 9
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JAN
PY 2014
VL 13
IS 1
BP 82
EP 89
DI 10.1158/1535-7163.MCT-13-0726
PG 8
WC Oncology
SC Oncology
GA 291GE
UT WOS:000329815200009
PM 24145282
ER
PT J
AU Maede, Y
Shimizu, H
Fukushima, T
Kogame, T
Nakamura, T
Miki, T
Takeda, S
Pommier, Y
Murai, J
AF Maede, Yuko
Shimizu, Hiroyasu
Fukushima, Toru
Kogame, Toshiaki
Nakamura, Terukazu
Miki, Tsuneharu
Takeda, Shunichi
Pommier, Yves
Murai, Junko
TI Differential and Common DNA Repair Pathways for Topoisomerase I- and
II-Targeted Drugs in a Genetic DT40 Repair Cell Screen Panel
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID ANTITUMOR DRUGS; DAMAGE; COMPLEXES; PHOSPHODIESTERASE; INHIBITORS;
CLEAVAGE; YEAST; ENZYME; TDP1; ANTICANCER
AB Clinical topoisomerase I (Top1) and II (Top2) inhibitors trap topoisomerases on DNA, thereby inducing protein-linked DNA breaks. Cancer cells resist the drugs by removing topoisomerase-DNA complexes, and repairing the drug-induced DNA double-strand breaks (DSB) by homologous recombination and nonhomologous end joining (NHEJ). Because numerous enzymes and cofactors are involved in the removal of the topoisomerase-DNA complexes and DSB repair, it has been challenging to comprehensively analyze the relative contribution of multiple genetic pathways in vertebrate cells. Comprehending the relative contribution of individual repair factors would give insights into the lesions induced by the inhibitors and genetic determinants of response. Ultimately, this information would be useful to target specific pathways to augment the therapeutic activity of topoisomerase inhibitors. To this end, we put together 48 isogenic DT40 mutant cells deficient in DNA repair and generated one cell line deficient in autophagy (ATG5). Sensitivity profiles were established for three clinically relevant Top1 inhibitors (camptothecin and the indenoisoquinolines LMP400 and LMP776) and three Top2 inhibitors (etoposide, doxorubicin, and ICRF-193). Highly significant correlations were found among Top1 inhibitors as well as Top2 inhibitors, whereas the profiles of Top1 inhibitors were different from those of Top2 inhibitors. Most distinct repair pathways between Top1 and Top2 inhibitors include NHEJ, TDP1, TDP2, PARP1, and Fanconi Anemia genes, whereas homologous recombination seems relevant especially for Top1 and, to a lesser extent, for Top2 inhibitors. We also found and discuss differential pathways among Top1 inhibitors and Top2 inhibitors. (C)2013 AACR.
C1 [Maede, Yuko; Kogame, Toshiaki; Takeda, Shunichi; Murai, Junko] Kyoto Univ, Dept Radiat Genet, Grad Sch Med, Kyoto, Japan.
[Fukushima, Toru] Kyoto Univ, Grad Sch Med, Dept Diabet & Clin Nutr, Kyoto, Japan.
[Nakamura, Terukazu] Kyoto Prefectural Univ, Dept Urol, Grad Sch Med, Kyoto 606, Japan.
[Shimizu, Hiroyasu; Miki, Tsuneharu] Osaka Med Coll, Dept Hyg & Publ Hlth, Osaka, Japan.
[Pommier, Yves; Murai, Junko] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM pommier@nih.gov; murai@rg.med.kyoto-u.ac.jp
FU Japan Society for the Promotion of Science (JSPS); Kyoto University
Foundation; Intramural Program of the National Cancer Institute, Center
for Cancer Research [Z01 BC 006150]; JSPS Core-to-Core Program
FX J. Murai is a recipient of a fellowship from the Japan Society for the
Promotion of Science (JSPS) and the Kyoto University Foundation. Y.
Pommier and J. Murai were supported by the Intramural Program of the
National Cancer Institute, Center for Cancer Research (Z01 BC 006150).
Y. Maede, H. Shimizu, and S. Takeda were supported by the JSPS
Core-to-Core Program.
NR 40
TC 36
Z9 37
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JAN
PY 2014
VL 13
IS 1
BP 214
EP 220
DI 10.1158/1535-7163.MCT-13-0551
PG 7
WC Oncology
SC Oncology
GA 291GE
UT WOS:000329815200021
PM 24130054
ER
PT J
AU Pan, J
Zhang, Q
Xiong, DH
Vedell, P
Yan, Y
Jiang, H
Cui, P
Ding, F
Tichelaar, JW
Wang, Y
Lubet, RA
You, M
AF Pan, Jing
Zhang, Qi
Xiong, Donghai
Vedell, Peter
Yan, Ying
Jiang, Hui
Cui, Peng
Ding, Feng
Tichelaar, Jay W.
Wang, Yian
Lubet, Ronald A.
You, Ming
TI Transcriptomic Analysis by RNA-Seq Reveals AP-1 Pathway as Key Regulator
that Green Tea May Rely on to Inhibit Lung Tumorigenesis
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE lung cancer; green tea; AP-1
ID C-JUN; (-)-EPIGALLOCATECHIN GALLATE; INDUCED TRANSFORMATION; TUMOR
PROMOTION; POLYPHENON-E; A/J MICE; CANCER; EXPRESSION; CARCINOGENESIS;
GROWTH
AB Green tea is a promising chemopreventive agent for lung cancer. Multiple signaling events have been reported, however, the relative importance of these mechanisms in mediating the chemopreventive function of green tea is unclear. In the present study, to examine the involvement of AP-1 in green tea polyphenols induced tumor inhibition, human NSCLC cell line H1299 and mouse SPON 10 cells were identified as AP-1 dependent, as these two lines exhibit high constitutive AP-1 activity, and when TAM67 expression was induced with doxycycline, cell growth was inhibited and correlated with suppressed AP-1 activity. RNA-seq was used to determine the global transcriptional effects of AP-1 inhibition and also uncover the possible involvement of AP-1 in tea polyphenols induced chemoprevention. TAM67 mediated changes in gene expression were identified, and within down-regulated genes, AP-1 was identified as a key transcription regulator. RNA-seq analysis revealed that Polyphenon E-treated cells shared 293 commonly down-regulated genes within TAM67 expressing H1299 cells, and by analysis of limited Chip-seq data, over 10% of the down-regulated genes contain a direct AP-1 binding site, indicating that Polyphenon E elicits chemopreventive activity by regulating AP-1 target genes. Conditional TAM67 expressing transgenic mice and NSCLC cell lines were used to further confirm that the chemopreventive activity of green tea is AP-1 dependent. Polyphenon E lost its chempreventive function both in vitro and in vivo when AP-1 was inhibited, indicating that AP-1 inhibition is a major pathway through which green tea exhibits chemopreventive effects. (c) 2013 Wiley Periodicals, Inc.
C1 [Pan, Jing; Yan, Ying; Wang, Yian; You, Ming] Washington Univ, Sch Med, Dept Surg, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
[Pan, Jing; Zhang, Qi; Xiong, Donghai; Vedell, Peter; Jiang, Hui; Cui, Peng; Ding, Feng; Tichelaar, Jay W.; You, Ming] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Ctr Canc, Milwaukee, WI 53226 USA.
[Lubet, Ronald A.] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA.
RP You, M (reprint author), Med Coll Wisconsin, Dept Pharmacol & Toxicol, Ctr Canc, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
NR 34
TC 1
Z9 2
U1 1
U2 41
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
EI 1098-2744
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD JAN
PY 2014
VL 53
IS 1
BP 19
EP 29
DI 10.1002/mc.21941
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 271CP
UT WOS:000328368400003
PM 24343902
ER
PT J
AU Wendell, CR
Waldstein, SR
Zonderman, AB
AF Wendell, Carrington R.
Waldstein, Shari R.
Zonderman, Alan B.
TI Nonlinear Longitudinal Trajectories of Cholesterol and
Neuropsychological Function
SO NEUROPSYCHOLOGY
LA English
DT Article
DE cholesterol; neuropsychology; cognitive decline; longitudinal
ID COGNITIVE DECLINE; LATE-LIFE; SERUM-CHOLESTEROL; ALZHEIMERS-DISEASE;
PERFORMANCE; POPULATION; DEMENTIA; ASSOCIATIONS; IMPAIRMENT; STATINS
AB Objective: Prior literature has identified inconsistent longitudinal associations between total cholesterol and cognitive decline. The authors examined prospective nonlinear relations of coincident trajectories of total cholesterol and cognitive function among persons free of stroke, dementia, and other neurological disease. Method: Up to 1,601 participants from the Baltimore Longitudinal Study of Aging (aged 19-93, 51% male, 75% White) underwent fasting cholesterol measurement and neuropsychological assessment on up to 12 occasions (M = 3.2, SD = 2.1) over up to 19 years (M = 6.4, SD = 5.3) of follow-up. Mixed-effects regression analyses were adjusted for age, sex, race, education, systolic blood pressure, body mass index, cardiovascular disease, lipid-lowering medication use, smoking, alcohol use, and depressive symptoms. Results: Analyses revealed significant longitudinal associations between quadratic total cholesterol and performance on measures of global mental status, verbal learning, executive function, and language (all ps < .05). In general, higher total cholesterol was associated with poorer middle-aged or young-old (60-69 years) cognitive performance, but better old-old (80-89 years) cognitive performance. Linear models also revealed an association between lower total cholesterol and accelerated decline in visual memory performance. Conclusions: Overall, results indicate nonlinear longitudinal relations of total cholesterol to cognitive decline. Whereas higher cholesterol levels were associated with cognitive decline in the middle-aged or young-old, lower cholesterol levels were related to cognitive decline among old-old participants.
C1 [Wendell, Carrington R.; Zonderman, Alan B.] NIH, Bethesda, MD USA.
[Wendell, Carrington R.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21218 USA.
[Wendell, Carrington R.; Waldstein, Shari R.] Univ Maryland, College Pk, MD 20742 USA.
[Waldstein, Shari R.] Univ Maryland, Sch Med, College Pk, MD 20742 USA.
[Waldstein, Shari R.] Baltimore VA Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
RP Wendell, CR (reprint author), NIA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM cwendell@jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging.
NR 35
TC 5
Z9 5
U1 0
U2 6
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
EI 1931-1559
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD JAN
PY 2014
VL 28
IS 1
BP 106
EP 112
DI 10.1037/neu0000002
PG 7
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 281RO
UT WOS:000329118900012
PM 24188111
ER
PT J
AU McPherson, CA
Merrick, BA
Harry, GJ
AF McPherson, C. A.
Merrick, B. A.
Harry, G. J.
TI In Vivo Molecular Markers for Pro-inflammatory Cytokine M1 Stage and
Resident Microglia in Trimethyltin-Induced Hippocampal Injury
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE M1 microglia; Neuroinflammation; Trimethyltin; Tumor necrosis factor;
Microglia polarization
ID NECROSIS-FACTOR-ALPHA; NICOTINIC ACETYLCHOLINE-RECEPTORS; QUANTITATIVE
NUCLEASE PROTECTION; B-CELL LYMPHOMA; GENE-EXPRESSION; MESSENGER-RNA;
DENTATE GYRUS; ALTERNATIVE ACTIVATION; INDUCED APOPTOSIS; GRANULE
NEURONS
AB Microglia polarization to the classical M1 activation state is characterized by elevated pro-inflammatory cytokines; however, a full profile has not been generated in the early stages of a sterile inflammatory response recruiting only resident microglia. We characterized the initial M1 state in a hippocampal injury model dependent upon tumor necrosis factor (TNF) receptor signaling for dentate granule cell death. Twenty-one-day-old CD1 male mice were injected with trimethyltin (TMT 2.3 mg/kg, i.p.) and the hippocampus was examined at an early stage (24-h post-dosing) of neuronal death. Glia activation was assessed using a custom quantitative nuclease protection assay. We report elevated mRNA levels for glia response such as ionizing calcium-binding adapter molecule-1 and glial fibrillary acidic protein (Gfap); Fas, hypoxia inducible factor alpha, complement component 1qb, TNF-related genes (Tnf, Tnfaip3, Tnfrsfla); interleukin-1 alpha, Cd44, chemokine (C-C motif) ligand (Ccl)2, Cc14, integrin alpha M, lipocalin (Lcn2), and secreted phosphoprotein 1 (Spp1). These changes occurred in the absence of changes in matrix metalloproteinase 9 and 12, neural cell adhesion molecule, metabotropic glutamate receptor (Grm)3, and Ly6/neurotoxin 1 (Lynx1), as well as, a decrease in neurotrophin 3, glutamate receptor subunit epsilon (Grin)-2b, and neurotrophic tyrosine kinase receptor, type 3. The M2 anti-inflammatory marker, transforming growth factor beta-1 (Tgfb1) was elevated. mRNAs associated with early stage of injury-induced neurogenesis including fibroblast growth factor 21 and Mki67 were elevated. In the "non-injured" temporal cortex receiving projections from the hippocampus, Lynx1, Grm3, and Grin2b were decreased and Gfap increased. Formalin fixed-paraffin-embedded tissue did not generate a comparable profile.
C1 [McPherson, C. A.; Harry, G. J.] NIEHS, Neurotoxicol Grp, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Merrick, B. A.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Harry, GJ (reprint author), NIEHS, Neurotoxicol Grp, Div Natl Toxicol Program, NIH, POB 12233,MD E1-07, Res Triangle Pk, NC 27709 USA.
EM harry@niehs.nih.gov
FU Division of Intramural Research and the Division National Toxicology
Program, NIEHS/NIH [1Z01ES101623]
FX The authors thank the NIEHS Microarray Core for their expert assistant
with the initial microarray analysis used for selection of qNPA probes,
Dr. Grace Kissling for statistical expertise, and Drs. Stephanie L.
Smith-Roe and Chad Blystone of NIEHS for reviewing the final manuscript.
This study was funded by the Division of Intramural Research and the
Division National Toxicology Program, NIEHS/NIH (1Z01ES101623). The qNPA
was conducted at HTG under an NTP contract with technical expertise from
Dr John Luecke. The statements, opinions, or conclusions contained
within this manuscript do not necessarily represent the statements,
opinions, or conclusions of NIEHS, NIH, or the United States Government.
NR 73
TC 11
Z9 11
U1 1
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
EI 1476-3524
J9 NEUROTOX RES
JI Neurotox. Res.
PD JAN
PY 2014
VL 25
IS 1
BP 45
EP 56
DI 10.1007/s12640-013-9422-3
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 284NR
UT WOS:000329326600005
PM 24002884
ER
PT J
AU Svetkey, LP
Clark, JM
Funk, K
Corsino, L
Batch, BC
Hollis, JF
Appel, LJ
Brantley, PJ
Loria, CM
Champagne, CM
Vollmer, WM
Stevens, VJ
AF Svetkey, Laura P.
Clark, Jeanne M.
Funk, Kristine
Corsino, Leonor
Batch, Bryan C.
Hollis, Jack F.
Appel, Lawrence J.
Brantley, Phillip J.
Loria, Catherine M.
Champagne, Catherine M.
Vollmer, William M.
Stevens, Victor J.
TI Greater weight loss with increasing age in the weight loss maintenance
trial
SO OBESITY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS; LIFE-STYLE
INTERVENTION; DISEASE RISK-FACTORS; ALL-CAUSE MORTALITY; BODY-MASS
INDEX; BLOOD-PRESSURE; HYPERTENSION PREVENTION; OLDER PERSONS; OBESITY
AB Objective To determine the effect of age on weight loss and weight loss maintenance in participants in the Weight Loss Maintenance trial (WLM). Design and Methods Secondary analysis of a randomized controlled trial of overweight/obese adults with CVD risk factors was conducted. Participants were 1685 adults with baseline BMI 25-45 kg m2 with hypertension and/or dyslipidemia. Those who lost at least 4kg in an initial 6-month behavioral weight loss intervention (N = 1,032) were randomly assigned to a 30-month maintenance phase of self-directed control (SD), monthly personal counseling (PC), or unlimited access to an internet-based intervention (IT). Age groups were defined post-hoc and weight change was compared among age groups. Results Participants 60 years old initially lost more weight than younger individuals, and sustained greater weight loss in IT and PC but not in SD (P value for trend 0.024, 0.002, and 0.36, respectively). Conclusions In WLM, adults age 60 years had greater initial weight loss and greater sustained weight loss over 3 years, compared to younger adults. Older adults had greater weight loss maintenance with either personal counseling or internet-based intervention. Future research should determine optimal implementation strategies and effects of weight loss on health outcomes in older adults.
C1 [Svetkey, Laura P.] Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA.
[Svetkey, Laura P.] Duke Univ, Med Ctr, Duke Hypertens Ctr, Durham, NC 27710 USA.
[Svetkey, Laura P.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA.
[Clark, Jeanne M.; Appel, Lawrence J.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Funk, Kristine; Hollis, Jack F.; Vollmer, William M.; Stevens, Victor J.] Kaiser Permanente Northwest, Ctr Hlth Res, Hlth Sci Programs, Portland, OR USA.
[Corsino, Leonor; Batch, Bryan C.] Duke Univ, Med Ctr, Dept Med, Div Endocrinol, Durham, NC 27710 USA.
[Brantley, Phillip J.; Champagne, Catherine M.] Louisiana State Univ, Pennington Biomed Res Ctr, Behav Med Lab, Baton Rouge, LA 70808 USA.
[Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Svetkey, LP (reprint author), Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA.
FU National Heart, Lung, Blood Institute [5-U01 HL68734, 5-U01 HL68676,
5-U01 HL68790, 5-U01 HL68920, 5-HL68955]
FX National Heart, Lung, Blood Institute grants 5-U01 HL68734, 5-U01
HL68676, 5-U01 HL68790, 5-U01 HL68920, and 5-HL68955.
NR 39
TC 6
Z9 6
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD JAN
PY 2014
VL 22
IS 1
BP 39
EP 44
DI 10.1002/oby.20506
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 288LN
UT WOS:000329613600010
PM 23640912
ER
PT J
AU Xiao, Q
Hsing, AW
Park, Y
Moore, SC
Matthews, CE
de Gonzalez, AB
Kitahara, CM
AF Xiao, Qian
Hsing, Ann W.
Park, Yikyung
Moore, Steven C.
Matthews, Charles E.
de Gonzalez, Amy Berrington
Kitahara, Cari M.
TI Body mass index and mortality among blacks and whites adults in the
Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
SO OBESITY
LA English
DT Article
ID ALL-CAUSE MORTALITY; US ADULTS; WAIST CIRCUMFERENCE; PROSPECTIVE COHORT;
ABDOMINAL OBESITY; WOMEN; RISK; WEIGHT; BMI; FAT
AB Objective In a large prospective cohort, we examined the relationship of body mass index (BMI) with mortality among blacks and compared the results to those among whites in this population. Design and Methods The study population consisted of 7,446 non-Hispanic black and 130,598 white participants, ages 49-78 at enrollment, in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. BMI at baseline, BMI at age 20, and BMI change were calculated using self-reported and recalled height and weight. Relative risks were stratified by race and sex and adjusted for age, education, marital status, and smoking. Results During follow-up, 1,495 black and 18,236 white participants died (mean = 13 years). Clear J-shaped associations between BMI and mortality were observed among white men and women. Among black men and women, the bottoms of these curves were flatter, and increasing risks of death with greater BMI were observed only at higher BMI levels (35.0). Associations for BMI at age 20 and BMI change also appeared to be stronger in magnitude in whites versus blacks, and these racial differences appeared to be more pronounced among women. Conclusion Our results suggest that BMI may be more weakly associated with mortality in blacks, particularly black women, than in whites.
C1 [Xiao, Qian; Park, Yikyung; Moore, Steven C.; Matthews, Charles E.; de Gonzalez, Amy Berrington; Kitahara, Cari M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hsing, Ann W.] Stanford Canc Inst, Canc Prevent Inst Calif, Fremont, CA USA.
RP Xiao, Q (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM qian.xiao@nih.gov
RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016; Kitahara,
Cari/R-8267-2016;
OI matthews, Charles/0000-0001-8037-3103; Moore,
Steven/0000-0002-8169-1661; Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services.
NR 38
TC 4
Z9 4
U1 2
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD JAN
PY 2014
VL 22
IS 1
BP 260
EP 268
DI 10.1002/oby.20412
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 288LN
UT WOS:000329613600038
PM 23512729
ER
PT J
AU Srinivasan, S
Williams, SD
AF Srinivasan, Shobha
Williams, Shanita D.
TI Transitioning from Health Disparities to a Health Equity Research
Agenda: The Time Is Now
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID ASTHMA
AB Health disparities are real. The evidence base is large and irrefutable. As such, the time is now to shift the research emphasis away from solely documenting the pervasiveness of the health disparities problem and begin focusing on health equity, the highest level of health possible. The focus on health equity research will require investigators to propose projects that develop and evaluate evidence-based solutions to health differences that are driven largely by social, economic, and environmental factors. This article highlights ongoing research and programmatic efforts underway at the National Institutes of Health that hold promise for advancing population health and improving health equity.
C1 [Srinivasan, Shobha] NCI, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Williams, Shanita D.] Bur Hlth Profess, US Dept HHS, US Hlth Resources & Serv Adm, Div Nursing, Rockville, MD USA.
RP Srinivasan, S (reprint author), NCI, US Dept HHS, NIH, 9609 Med Ctr Dr,Room 4E432,MSC 9764, Bethesda, MD 20892 USA.
EM ss688k@nih.gov
NR 23
TC 5
Z9 5
U1 0
U2 3
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD JAN-FEB
PY 2014
VL 129
SU 2
BP 71
EP 76
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 288BN
UT WOS:000329587100013
PM 24385668
ER
PT J
AU Koola, MM
Gorelick, DA
McMahon, RP
Liu, F
Huestis, MA
Linthicum, J
Feldman, SM
Warren, KR
Wehring, HJ
Kelly, DL
AF Koola, Maju Mathew
Gorelick, David A.
McMahon, Robert P.
Liu, Fang
Huestis, Marilyn A.
Linthicum, Jared
Feldman, Stephanie M.
Warren, Kimberly R.
Wehring, Heidi J.
Kelly, Deanna L.
TI Psychiatric symptom differences in people with schizophrenia associated
with substantial lifetime substance use but no current substance use
disorder
SO SCHIZOPHRENIA RESEARCH
LA English
DT Letter
ID DOUBLE-BLIND; RIMONABANT
C1 [Koola, Maju Mathew; Gorelick, David A.; McMahon, Robert P.; Liu, Fang; Linthicum, Jared; Feldman, Stephanie M.; Warren, Kimberly R.; Wehring, Heidi J.; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Koola, Maju Mathew] Sheppard Pratt Hlth Syst, Baltimore, MD 21204 USA.
[Gorelick, David A.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD USA.
[Warren, Kimberly R.] Morgan State Univ, Dept Psychol, Baltimore, MD 21239 USA.
RP Koola, MM (reprint author), Sheppard Pratt Hlth Syst, Clin Res Program, Baltimore, MD 21204 USA.
EM majujuju@yahoo.com
FU Intramural NIH HHS [Z99 DA999999]; NIMH NIH HHS [R34 MH077839, R34 MH
077839]; PHS HHS [P30 068580, HSN271200599091CADB]
NR 6
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD JAN
PY 2014
VL 152
IS 1
BP 315
EP 316
DI 10.1016/j.schres.2013.11.035
PG 2
WC Psychiatry
SC Psychiatry
GA 283AR
UT WOS:000329217000052
PM 24333005
ER
PT J
AU Agnihothri, RV
Courville, AB
Linderman, JD
Smith, S
Brychta, R
Remaley, A
Chen, KY
Simchowitz, L
Celi, FS
AF Agnihothri, Ritesh V.
Courville, Amber B.
Linderman, Joyce D.
Smith, Sheila
Brychta, Robert
Remaley, Alan
Chen, Kong Y.
Simchowitz, Louis
Celi, Francesco S.
TI Moderate Weight Loss Is Sufficient to Affect Thyroid Hormone Homeostasis
and Inhibit Its Peripheral Conversion
SO THYROID
LA English
DT Article
ID BODY-MASS INDEX; RESTING METABOLIC-RATE; ENERGY-EXPENDITURE; EUTHYROID
SUBJECTS; LOSS MAINTENANCE; MAJOR SOURCE; US ADULTS; FREE T4; OBESITY;
TRIIODOTHYRONINE
AB Background: Thyroid hormones are important determinants of energy expenditure, and in rodents, adipose tissue affects thyroid hormone homeostasis via leptin signaling. The relationship between thyroid hormones and nutritional status in humans has been assessed primarily in drastic dietary or bariatric surgery interventions, while limited information is available on serial assessment of this axis during moderate, prolonged dietary restriction. Methods: To evaluate the effects of moderate dietary restriction on thyroid hormone homeostasis, 47 subjects with a body mass index (BMI) of 25-45kg/m(2) were enrolled in a longitudinal intervention study; 30 nonoverweight volunteers were also enrolled as controls. Overweight and obese subjects underwent a 12-month individualized dietary intervention aimed at achieving a 5-10% weight loss. Results: The intervention resulted in a 6.30.9kg (6.5 +/- 1.0%) weight loss. At baseline, thyrotropin (TSH) and T3 concentrations correlated significantly with fat mass (R=0.257, p=0.024 and R=0.318, p=0.005, respectively). After weight loss, T3 decreased significantly (from 112.7 +/- 3.1 to 101.8 +/- 2.6ng/dL, p<0.001) in the absence of significant changes in TSH or free T4 (fT4). The decrease in serum T3 correlated with the decrease in weight (R=0.294, p<0.001). The T3:fT4 ratio decreased significantly (p=0.02) in individuals who lost >5% body weight. Conclusions: T3 concentration closely correlates with individual nutritional status, and moderate weight loss results in a decrease in T3 with minimal changes in other thyroid hormone homeostasis parameters. The data suggest that a decrease in peripheral conversion of the prohormone T4 into its hormonally active metabolite T3 is at least in part responsible for the observed changes in thyroid hormone homeostasis.
C1 [Agnihothri, Ritesh V.; Linderman, Joyce D.; Smith, Sheila; Brychta, Robert; Chen, Kong Y.; Simchowitz, Louis; Celi, Francesco S.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Simchowitz, Louis] Natl Inst Diabet & Digest & Kidney Dis, Off Director, Bethesda, MD 20892 USA.
[Courville, Amber B.] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Remaley, Alan] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Celi, FS (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrinol & Obes Branch, NIH, CRC, Bldg 10,RM 6-3940 10 Ctr Dr,MSC 1613, Bethesda, MD 20892 USA.
EM fsceli@vcu.edu
OI Chen, Kong/0000-0002-0306-1904
FU Intramural Research Program of the NIDDK program [Z01-DK047057-02];
Clinical Center, NIH
FX The authors gratefully acknowledge the help and professionalism of the
nursing, Nutrition Department, laboratory, and ancillary personnel of
the NIH Metabolic Unit. The technical help of Mary Walter and Xiongce
Zhao and the constructive criticism of Paul Lee are gratefully
acknowledged. This research could not have been accomplished without the
selfless participation of the study volunteers. This work was supported
by the Intramural Research Program of the NIDDK program Z01-DK047057-02,
and the Clinical Center, NIH.
NR 46
TC 13
Z9 13
U1 2
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD JAN 1
PY 2014
VL 24
IS 1
BP 19
EP 26
DI 10.1089/thy.2013.0055
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 285YM
UT WOS:000329431000004
PM 23902316
ER
PT J
AU McLeod, DSA
Cooper, DS
Ladenson, PW
Ain, KB
Brierley, JD
Fein, HG
Haugen, BR
Jonklaas, J
Magner, J
Ross, DS
Skarulis, MC
Steward, DL
Maxon, HR
Sherman, SI
AF McLeod, Donald S. A.
Cooper, David S.
Ladenson, Paul W.
Ain, Kenneth B.
Brierley, James D.
Fein, Henry G.
Haugen, Bryan R.
Jonklaas, Jacqueline
Magner, James
Ross, Douglas S.
Skarulis, Monica C.
Steward, David L.
Maxon, Harry R.
Sherman, Steven I.
CA Natl Thyroid Canc Treatment Cooper
TI Prognosis of Differentiated Thyroid Cancer in Relation to Serum
Thyrotropin and Thyroglobulin Antibody Status at Time of Diagnosis
SO THYROID
LA English
DT Article
ID CHRONIC LYMPHOCYTIC THYROIDITIS; STAGING SYSTEMS; PAPILLARY; CARCINOMA;
RISK; DISEASE; TSH; SUPPRESSION; PROGRESSION; RECURRENCE
AB Background: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis. Objective: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry. Methods: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) or perioperative TgAb status (n=1770; the TgAb cohort) were analyzed for tumor stage, persistent disease, recurrence, and overall survival (OS; median follow-up, 5.5 years). Parametric tests assessed log-transformed TSH, and categorical variables were tested with chi square. Disease-free survival (DFS) and OS was assessed with Cox models. Results: Geometric mean serum TSH levels were higher in patients with higher-stage disease (Stage III/IV=1.48 vs. 1.02mU/L for Stages I/II; p=0.006). The relationship persisted in those aged 45 years after adjusting for sex (p=0.01). Gross extrathyroidal extension (p=0.03) and presence of cervical lymph node metastases (p=0.003) were also significantly associated with higher serum TSH. Disease recurrence and all-cause mortality occurred in 37 and 38 TSH cohort patients respectively, which limited the power for survival analysis. Positive TgAb was associated with lower stage on univariate analysis (positive TgAb in 23.4% vs. 17.8% of Stage I/II vs. III/IV patients, respectively; p=0.01), although the relationship lost significance when adjusting for age and sex (p=0.34). Perioperative TgAb was not an independent predictor of DFS (hazard ratio=1.12 [95% confidence interval=0.74-1.69]) or OS (hazard ratio=0.98 [95% confidence interval=0.56-1.72]). Conclusions: Preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases. Perioperative TgAb is not an independent predictor of DTC prognosis. A larger cohort is required to assess whether preoperative serum TSH level predicts recurrence or mortality.
C1 [McLeod, Donald S. A.] Royal Brisbane & Womens Hosp, Dept Internal Med & Aged Care, Herston, Qld 4029, Australia.
[McLeod, Donald S. A.] Royal Brisbane & Womens Hosp, Dept Endocrinol, Herston, Qld 4029, Australia.
[McLeod, Donald S. A.] Queensland Inst Med Res, Canc Control Grp, Herston, Qld 4006, Australia.
[Cooper, David S.; Ladenson, Paul W.] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD USA.
[Ain, Kenneth B.] Vet Affairs Med Ctr, Dept Internal Med, Lexington, KY USA.
[Ain, Kenneth B.] Univ Kentucky, Lexington, KY USA.
[Brierley, James D.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada.
[Fein, Henry G.] Sinai Hosp, Div Endocrinol & Metab, Baltimore, MD 21215 USA.
[Haugen, Bryan R.] Univ Colorado, Sch Med, Div Endocrinol Metab & Diabet, Aurora, CO USA.
[Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Dept Med, Div Endocrinol, Washington, DC 20007 USA.
[Magner, James] Genzyme Corp, Cambridge, MA USA.
[Ross, Douglas S.] Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA.
[Skarulis, Monica C.] NIH, Diabet Endocrinol Obes Branch, Bethesda, MD 20892 USA.
[Steward, David L.] Univ Cincinnati, Med Ctr, Dept Head & Neck Surg, Cincinnati, OH 45267 USA.
[Maxon, Harry R.] Univ Cincinnati, Med Ctr, Dept Nucl Med, Cincinnati, OH 45267 USA.
[Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA.
RP McLeod, DSA (reprint author), Royal Brisbane & Womens Hosp, Dept Internal Med & Aged Care, Herston, Qld 4029, Australia.
EM donald.mcleod@qimr.edu.au
RI Jonklaas, Jacqueline/G-2807-2010; McLeod, Donald/C-4242-2014;
OI Jonklaas, Jacqueline/0000-0002-2238-2666; McLeod,
Donald/0000-0003-1131-020X; Sherman, Steven/0000-0002-3079-5153
FU Genzyme Corporation; Pfizer; University of Texas M.D. Anderson Cancer
Center Support Grant (NCI Grant) [P30 CA016672]; Royal Australasian
College of Physicians IMS Traveling Fellowship; Cancer Council
Queensland PhD scholarship
FX The NTCTCSG is supported in part by research grants from Genzyme
Corporation and Pfizer, and by the University of Texas M.D. Anderson
Cancer Center Support Grant (NCI Grant P30 CA016672). A Royal
Australasian College of Physicians IMS Traveling Fellowship and a Cancer
Council Queensland PhD scholarship supported D. S. A. M. We, as
principal investigators at each NTCTCSG institution, thank the
physicians and staff members who participated in the management and
follow-up of these patients. We acknowledge the substantial
contributions of the institutional research staff that collected and
submitted the data, including Shehnaz Bana, Marge E. Ewertz, RN, and
Beverly McLaughlin, RMA. We also appreciate the considerable assistance
provided by Jeffrey Cui for the management of NTCTCSG's databases.
Finally, we acknowledge the efforts of the numerous physicians and
scientists whose contributions were critical in the early years of the
registry.
NR 37
TC 25
Z9 25
U1 0
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD JAN 1
PY 2014
VL 24
IS 1
BP 35
EP 42
DI 10.1089/thy.2013.0062
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 285YM
UT WOS:000329431000006
PM 23731273
ER
PT J
AU Bianco, AC
Anderson, G
Forrest, D
Galton, VA
Gereben, B
Kim, BW
Kopp, PA
Liao, XH
Obregon, MJ
Peeters, RP
Refetoff, S
Sharlin, DS
Simonides, WS
Weiss, RE
Williams, GR
AF Bianco, Antonio C.
Anderson, Grant
Forrest, Douglas
Galton, Valerie Anne
Gereben, Balazs
Kim, Brian W.
Kopp, Peter A.
Liao, Xiao Hui
Obregon, Maria Jesus
Peeters, Robin P.
Refetoff, Samuel
Sharlin, David S.
Simonides, Warner S.
Weiss, Roy E.
Williams, Graham R.
TI American Thyroid Association Guide to Investigating Thyroid Hormone
Economy and Action in Rodent and Cell Models
SO THYROID
LA English
DT Article
ID TYPE-2 IODOTHYRONINE DEIODINASE; BROWN ADIPOSE-TISSUE;
THYROTROPIN-RELEASING-HORMONE; MYOSIN HEAVY-CHAIN;
MESSENGER-RIBONUCLEIC-ACID; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS;
SARCOPLASMIC-RETICULUM CA2+-ATPASE; RAT SKELETAL-MUSCLE;
ANTERIOR-PITUITARY-CELLS; SODIUM-IODIDE SYMPORTER
AB Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyperthyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes.
C1 [Bianco, Antonio C.; Kim, Brian W.] Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA.
[Anderson, Grant] Univ Minnesota, Coll Pharm, Dept Pharm Practice & Pharmaceut Sci, Duluth, MN 55812 USA.
[Forrest, Douglas] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Galton, Valerie Anne] Dartmouth Med Sch, Dept Physiol & Neurobiol, Lebanon, NH USA.
[Gereben, Balazs] Hungarian Acad Sci, Inst Expt Med, Dept Endocrine Neurobiol, Budapest, Hungary.
[Kopp, Peter A.] Northwestern Univ, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[Kopp, Peter A.] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA.
[Liao, Xiao Hui; Refetoff, Samuel; Weiss, Roy E.] Univ Chicago, Sect Adult & Pediat Endocrinol Diabet & Metab, Chicago, IL 60637 USA.
[Obregon, Maria Jesus] CSIC, Inst Invest Biomed, Spanish Natl Res Council, Madrid, Spain.
[Obregon, Maria Jesus] Autonomous Univ Madrid, E-28049 Madrid, Spain.
[Peeters, Robin P.] Erasmus MC, Dept Internal Med, Div Endocrinol, Rotterdam, Netherlands.
[Sharlin, David S.] Minnesota State Univ, Dept Biol Sci, Mankato, MN USA.
[Simonides, Warner S.] Vrije Univ Amsterdam Med Ctr, Inst Cardiovasc Res, Physiol Lab, Amsterdam, Netherlands.
[Williams, Graham R.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.
RP Bianco, AC (reprint author), Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Suite 816 Dominion Towers,1400 NW 10th Ave, Miami, FL 33136 USA.
EM abianco@deiodinase.org
RI Peeters, Robin/P-3603-2014
FU NIDDK at the National Institutes of Health; NIDDK [2R01-DK58538-08,
1R01-DK065055-02, R01-DK77148, R37DK015070, R21 HD 072526-02]; NICHD
[R03 HD061901]; MINECO [SAF2012-32491]; CAM [S2010/BMD-2423];
U.S.-Israel Binational Science Foundation; National Science Foundation
of Hungary [OTKA K81226]; European Community [259772]; ZonMw Clinical
Fellowship Grant [90700412]; ZonMW TOP Grant [91212044]
FX This work was supported in part by the intramural research program of
NIDDK at the National Institutes of Health (to D.F.), NIDDK grants
2R01-DK58538-08, 1R01-DK065055-02, R01-DK77148 (to A. C. B.),
R37DK015070 (to X. H. L. and S. R.) and R21 HD 072526-02 (to V. A. G.),
NICHD grant R03 HD061901 (to P. A. K.), SAF2012-32491 from MINECO and
S2010/BMD-2423 from CAM (to M.J.O.), U.S.-Israel Binational Science
Foundation (to G. A.), National Science Foundation of Hungary (OTKA
K81226) and the European Community's Seventh Framework Programme
(FP7/2007-2013) under grant agreement no. 259772 (to B. G.), and the
ZonMw Clinical Fellowship Grant (90700412) and a ZonMW TOP Grant
(91212044) (to R.P.P.).
NR 725
TC 39
Z9 40
U1 3
U2 27
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD JAN 1
PY 2014
VL 24
IS 1
BP 88
EP 168
DI 10.1089/thy.2013.0109
PG 81
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 285YM
UT WOS:000329431000013
PM 24001133
ER
PT J
AU Danilenko, DM
Nambiar, PR
Cesta, MF
AF Danilenko, Dimitry M.
Nambiar, Prashant R.
Cesta, Mark F.
TI A Brief Overview of the 32nd Annual STP Symposium on the Toxicologic
Pathology of the Digestive Tract and Pancreas
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE digestive system; pancreas; toxicologic pathology; pathobiology
C1 [Danilenko, Dimitry M.] Genentech Inc, San Francisco, CA 94080 USA.
[Nambiar, Prashant R.] Pfizer Inc, Groton, CT 06340 USA.
[Cesta, Mark F.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Danilenko, DM (reprint author), Genentech Inc, 1 DNA Way MS-59, San Francisco, CA 94080 USA.
EM ddanilen@gene.com
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JAN
PY 2014
VL 42
IS 1
BP 45
EP 48
DI 10.1177/0192623313502402
PG 4
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 289MS
UT WOS:000329687200001
PM 24002990
ER
PT J
AU Lee, EB
Mattson, MP
AF Lee, Edward B.
Mattson, Mark P.
TI The neuropathology of obesity: insights from human disease
SO ACTA NEUROPATHOLOGICA
LA English
DT Review
ID BARDET-BIEDL-SYNDROME; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
BODY-MASS INDEX; PRADER-WILLI-SYNDROME; CONGENITAL LEPTIN DEFICIENCY;
INDUCED STATUS EPILEPTICUS; EARLY-ONSET OBESITY; Y GASTRIC BYPASS;
HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PENTYLENETETRAZOLE-INDUCED
SEIZURES
AB Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator, which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand's syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer's disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus, obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function, highlighting the need for continued clinicopathologic and mechanistic studies of the neuropathology of obesity.
C1 [Lee, Edward B.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Translat Neuropathol Res Lab,Div Neuropathol, Philadelphia, PA 19104 USA.
[Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Lee, EB (reprint author), Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Translat Neuropathol Res Lab,Div Neuropathol, 605B Stellar Chance Labs,422 Curie Blvd, Philadelphia, PA 19104 USA.
EM edward.lee@uphs.upenn.edu
FU National Institutes of Health [AG039510, DK19525, AG010124]; Intramural
Research Program of the National Institute on Aging
FX EBL is funded in part by grants from the National Institutes of Health
(AG039510, DK19525, AG010124) and MPM is funded in part by the
Intramural Research Program of the National Institute on Aging. EBL
thanks Dr. Rexford Ahima for useful discussions in developing this
review.
NR 269
TC 11
Z9 13
U1 4
U2 31
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD JAN
PY 2014
VL 127
IS 1
BP 3
EP 28
DI 10.1007/s00401-013-1190-x
PG 26
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 283DL
UT WOS:000329225300002
PM 24096619
ER
PT J
AU Cadet, JL
Bisagno, V
Milroy, CM
AF Cadet, Jean Lud
Bisagno, Veronica
Milroy, Christopher Mark
TI Neuropathology of substance use disorders
SO ACTA NEUROPATHOLOGICA
LA English
DT Review
DE Cannabis; Cocaine; Methamphetamine; MDMA; Heroin; Cathinones; Bath
salts; Dopamine; Toxicity; Frontal cortex; Hippocampus; Nucleus
accumbens; Striatum; Reward mechanisms
ID ABSTINENT METHAMPHETAMINE ABUSERS; VOXEL-BASED MORPHOMETRY; WHITE-MATTER
INTEGRITY; CENTRAL-NERVOUS-SYSTEM; COCAINE-DEPENDENT INDIVIDUALS;
POSITRON-EMISSION-TOMOGRAPHY; PSYCHOACTIVE BATH SALTS; HEAVY MARIJUANA
USERS; MDMA ECSTASY USERS; CANNABIS USE
AB Addictions to licit and illicit drugs are chronic relapsing brain disorders that affect circuits that regulate reward, motivation, memory, and decision-making. Drug-induced pathological changes in these brain regions are associated with characteristic enduring behaviors that continue despite adverse biopsychosocial consequences. Repeated exposure to these substances leads to egocentric behaviors that focus on obtaining the drug by any means and on taking the drug under adverse psychosocial and medical conditions. Addiction also includes craving for the substances and, in some cases, involvement in risky behaviors that can cause death. These patterns of behaviors are associated with specific cognitive disturbances and neuroimaging evidence for brain dysfunctions in a diverse population of drug addicts. Postmortem studies have also revealed significant biochemical and/or structural abnormalities in some addicted individuals. The present review provides a summary of the evidence that has accumulated over the past few years to implicate brain dysfunctions in the varied manifestations of drug addiction. We thus review data on cerebrovascular alterations, brain structural abnormalities, and postmortem studies of patients who abuse cannabis, cocaine, amphetamines, heroin, and "bath salts". We also discuss potential molecular, biochemical, and cellular bases for the varied clinical presentations of these patients. Elucidation of the biological bases of addiction will help to develop better therapeutic approaches to these patient populations.
C1 [Cadet, Jean Lud] NIDA NIH DHHS, NIDA Intramural Res Program, Mol Neuropsychiatry Res Branch, Baltimore, MD 21224 USA.
[Bisagno, Veronica] Inst Invest Farmacol ININFA UBA CONICET, Buenos Aires, DF, Argentina.
[Milroy, Christopher Mark] Ottawa Hosp, Div Anat Pathol, Eastern Ontario Forens Pathol, Unit Ontario Forens Pathol Serv, Ottawa, ON K2A 2L4, Canada.
RP Cadet, JL (reprint author), NIDA NIH DHHS, NIDA Intramural Res Program, Mol Neuropsychiatry Res Branch, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA), NIH; United States Department of State, Argentina
[PIP11420100100072, PICT 2012-0924]; DHHS
FX This paper is supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), NIH, and DHHS. V. Bisagno is a
Fulbright Fellow, United States Department of State and is also
supported by grants PIP11420100100072 and PICT 2012-0924, Argentina.
NR 209
TC 29
Z9 29
U1 12
U2 70
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD JAN
PY 2014
VL 127
IS 1
BP 91
EP 107
DI 10.1007/s00401-013-1221-7
PG 17
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA 283DL
UT WOS:000329225300006
PM 24292887
ER
PT J
AU Velagaleti, RS
Gona, P
Pencina, MJ
Aragam, J
Wang, TJ
Levy, D
D'Agostino, RB
Lee, DS
Kannel, WB
Benjamin, EJ
Vasan, RS
AF Velagaleti, Raghava S.
Gona, Philimon
Pencina, Michael J.
Aragam, Jayashri
Wang, Thomas J.
Levy, Daniel
D'Agostino, Ralph B.
Lee, Douglas S.
Kannel, William B.
Benjamin, Eme Lia J.
Vasan, Ramachandran S.
TI Left Ventricular Hypertrophy Patterns and Incidence of Heart Failure
With Preserved Versus Reduced Ejection Fraction
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID MYOCARDIAL-INFARCTION; DILATED CARDIOMYOPATHY; LONGITUDINAL TRACKING;
CARDIOVASCULAR HEALTH; HYPERTENSIVE PATIENTS; GEOMETRIC PATTERNS; WALL
STRESS; FRAMINGHAM; MASS; DISEASE
AB Higher left ventricular (LV) mass, wall thickness, and internal dimension are associated with increased heart failure (HF) risk. Whether different LV hypertrophy patterns vary with respect to rates and types of HF incidence is unclear. In this study, 4,768 Framingham Heart Study participants (mean age 50 years, 56% women) were classified into 4 mutually exclusive LV hypertrophy pattern groups (normal, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy) using American Society of Echocardiography recommended thresholds of echocardiographic LV mass indexed to body surface area and relative wall thickness, and these groups were related to HF incidence. Whether risk for HF types (HF with reduced ejection fraction [<45%] vs preserved ejection fraction [>= 45%]) varied by hypertrophy pattern was then evaluated. On follow-up (mean 21 years), 458 participants (9.6%, 250 women) developed new-onset HF. The age- and gender-adjusted 20-year HF incidence increased from 6.96% in the normal left ventricle group to 8.67%, 13.38%, and 15.27% in the concentric remodeling, concentric hypertrophy, and eccentric hypertrophy groups, respectively. After adjustment for co-morbidities and incident myocardial infarction, LV hypertrophy patterns were associated with higher HF incidence relative to the normal left ventricle group (p = 0.0002); eccentric hypertrophy carried the greatest risk (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.41 to 2.54), followed by concentric hypertrophy (HR 1.40, 95% CI 1.04 to 1.87). Participants with eccentric hypertrophy had a higher propensity for HF with reduced ejection fraction (HR 2.23, 95% CI 1.48 to 3.37), whereas those with concentric hypertrophy were more prone to HF with preserved ejection fraction (HR 1.66, 95% CI 1.09 to 2.51). In conclusion, in this large community-based sample, HF risk varied by LV hypertrophy pattern, with eccentric and concentric hypertrophy predisposing to HF with reduced and preserved ejection fraction, respectively. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Velagaleti, Raghava S.; Gona, Philimon; Pencina, Michael J.; Levy, Daniel; D'Agostino, Ralph B.; Kannel, William B.; Benjamin, Eme Lia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Velagaleti, Raghava S.] Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA USA.
[Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Aragam, Jayashri] Vet Adm Hosp, West Roxbury, MA USA.
[Aragam, Jayashri; Wang, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Lee, Douglas S.] Univ Toronto, Inst Clin Evaluat Sci, Toronto, ON, Canada.
[Lee, Douglas S.] Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada.
[Benjamin, Eme Lia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Eme Lia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
EM vasan@bu.edu
RI Lee, Douglas/J-4315-2014;
OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-25195]; National Institutes of Health, Bethesda, Maryland [RO1
HL67288]
FX This work was supported by the Contract N01-HC-25195 from the National
Heart, Lung, and Blood Institute, Bethesda, Maryland, and Grant RO1
HL67288 from the National Institutes of Health, Bethesda, Maryland.
NR 30
TC 25
Z9 25
U1 0
U2 8
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JAN 1
PY 2014
VL 113
IS 1
BP 117
EP 122
DI 10.1016/j.amjcard.2013.09.028
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 284QA
UT WOS:000329333800020
PM 24210333
ER
PT J
AU Roseman, DA
Hwang, SJ
Manders, ES
O'Donnell, CJ
Upadhyay, A
Hoffmann, U
Fox, CS
AF Roseman, Daniel A.
Hwang, Shih-Jen
Manders, Emily S.
O'Donnell, Christopher J.
Upadhyay, Ashish
Hoffmann, Udo
Fox, Caroline S.
TI Renal Artery Calcium, Cardiovascular Risk Factors, and Indexes of Renal
Function
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ANGIOTENSIN-ALDOSTERONE SYSTEM; VASCULAR CALCIFICATIONS;
COMPUTED-TOMOGRAPHY; KIDNEY-DISEASE; MICROALBUMINURIA; FRAMINGHAM;
STIFFNESS; ATHEROSCLEROSIS; RACE; MEN
AB Vascular calcium is well studied in the coronary and peripheral arteries, although there are limited data focusing on calcium deposits specific to renal arteries. The associations among renal artery calcium (RAC), cardiovascular disease risk factors, and indexes of renal function are unknown. We examined 2,699 Framingham Heart Study participants who were part of a multidetector computed tomography substudy from 2008 to 2011. RAC was measured as a calcified plaque of >130 HU and an area of >3 contiguous pixels. Detectable RAC was defined as an Agatston score >0. Chronic kidney disease was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m(2). Microalbuminuria was defined as an albumin/creatinine ratio of >= 17 mg/g for men and >= 25 mg/g for women. Multivariable adjusted logistic regression models were used to evaluate the associations between RAC, cardiovascular disease risk factors, and renal function. The associations were secondarily adjusted for coronary artery calcium (CAC) that was used as a marker of nonrenal systemic vascular calcium. The prevalence of RAC was 28.2%; this was similar in women (28.8%) and men (27.5%). Patients with RAC had a higher odds of microalbuminuria (Odds ratio [OR] 1.79, 95% confidence interval [CI] 1.22 to 2.61, p = 0.003), hypertension (OR 2.11, 95% CI 1.69 to 2.64, p<0.001), and diabetes (OR 1.60, 95% CI 1.14 to 2.24, p = 0.01) but not chronic kidney disease (OR 0.87, 95% CI 0.58 to 1.32). After adjustment for CAC, the association with microalbuminuria and hypertension persisted, but the association with diabetes became nonsignificant. In conclusion, RAC is common and independently associated with microalbuminuria and hypertension after adjustment for nonrenal vascular calcium. RAC may be uniquely associated with these markers of renal end-organ damage. Published by Elsevier Inc.
C1 [Roseman, Daniel A.; Upadhyay, Ashish] Boston Univ, Med Ctr, Renal Sect, Boston, MA USA.
[Hwang, Shih-Jen; Manders, Emily S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM foxca@nhlbi.nih.gov
OI Upadhyay, Ashish/0000-0002-0536-5776
FU Boston University from the National Heart, Lung, and Blood Institute
[N01-HC-25195]; National Institutes of Health (Bethesda, Maryland)
[T32-DK-007053]
FX The Framingham Heart Study is conducted and supported in collaboration
with Boston University by contract N01-HC-25195 from the National Heart,
Lung, and Blood Institute; Dr. Roseman received funding from grant
T32-DK-007053, National Institutes of Health (Bethesda, Maryland).
NR 25
TC 6
Z9 9
U1 0
U2 3
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JAN 1
PY 2014
VL 113
IS 1
BP 156
EP 161
DI 10.1016/j.amjcard.2013.09.036
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 284QA
UT WOS:000329333800027
PM 24210678
ER
PT J
AU Al-Mallah, MH
Nasir, K
Katz, R
Lima, JA
Bluemke, DA
Blumenthal, RS
Mao, SS
Hundley, WG
Budoff, MJ
AF Al-Mallah, Mouaz H.
Nasir, Khurram
Katz, Ronit
Lima, Joao A.
Bluemke, David A.
Blumenthal, Roger S.
Mao, Songshou
Hundley, W. Gregory
Budoff, Matthew J.
TI Relation of Thoracic Aortic Distensibility to Left Ventricular Area
(from the Multi-Ethnic Study of Atherosclerosis [MESA])
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID PROGNOSTIC VALUE; CARDIOVASCULAR MORTALITY; ESSENTIAL-HYPERTENSION;
INDEPENDENT PREDICTOR; COMPUTED-TOMOGRAPHY; ARTERIAL STIFFNESS; SCANNER
TYPE; ALL-CAUSE; HYPERTROPHY; CALCIFICATION
AB Decreased arterial compliance is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with left ventricular (LV) area on computed tomography, a marker of LV remodeling, has not been well demonstrated. The aim of this study was to test the hypothesis that decreasing aortic compliance and increasing arterial stiffness are independently associated. with increased LV area. The study population consisted of 3,540 patients (mean age 61 +/- 10 years, 46% men) from the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent aortic distensibility (AD) assessment on magnetic resonance imaging and LV area measurement on computed tomography (adjusted to body surface area). Multivariate logistic regression was performed to assess the association between body surface area-normalized LV area >75th percentile and AD after adjusting for baseline clinical, historical, and imaging covariates. Mean LV area index was 2,153 cm, and mean AD was 1.84 x 10(3) mm Hg-1. Subjects in the lowest AD quartile were older, with higher prevalence rates of hypertension, diabetes, and hypercholesterolemia (p<0.05 for all comparisons). Using multivariate linear regression adjusting for demographics, traditional risk factors, coronary artery calcium, and C-reactive protein, each SD decrease was associated with an 18-cm(2) increase in LV area. In addition, decreasing AD quartiles were independently associated with increasing LV area index, defined as >75th percentile. In conclusion, in this multiethnic cohort, reduced AD was associated with increased LV area. Longitudinal studies are needed to determine if decreased distensibility precedes and directly influences increased LV area. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Al-Mallah, Mouaz H.] Wayne State Univ, Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA.
[Al-Mallah, Mouaz H.] King Abdulaziz Cardiac Ctr, Div Cardiac Imaging, Riyadh, Saudi Arabia.
[Nasir, Khurram] Baptist Hlth Med Grp, Ctr Prevent & Wellness Res, Miami Beach, FL USA.
[Katz, Ronit] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Lima, Joao A.; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Dept Radiol & Imaging Sci, NIH, Bethesda, MD USA.
[Mao, Songshou; Budoff, Matthew J.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA 90509 USA.
[Hundley, W. Gregory] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27103 USA.
RP Al-Mallah, MH (reprint author), Wayne State Univ, Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA.
EM mouaz74@gmail.com
OI Bluemke, David/0000-0002-8323-8086; Al-Mallah, Mouaz/0000-0003-2348-0484
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [R01
HL071739, N01-HC-95159, N01-HC-95165, N01-HC-95169]
FX This research was supported by Grant R01 HL071739 and Contracts
N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National
Heart, Lung, and Blood Institute, Bethesda, Maryland.
NR 30
TC 2
Z9 2
U1 1
U2 4
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JAN 1
PY 2014
VL 113
IS 1
BP 178
EP 182
DI 10.1016/j.amjcard.2013.09.039
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 284QA
UT WOS:000329333800031
PM 24210674
ER
PT J
AU Hughey, CC
James, FD
Ma, LL
Bracy, DP
Wang, ZZ
Wasserman, DH
Rottman, JN
Shearer, J
AF Hughey, Curtis C.
James, Freyja D.
Ma, Lianli
Bracy, Deanna P.
Wang, Zhizhang
Wasserman, David H.
Rottman, Jeffrey N.
Shearer, Jane
TI Diminishing impairments in glucose uptake, mitochondrial content, and
ADP-stimulated oxygen flux by mesenchymal stem cell therapy in the
infarcted heart
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE mitochondria; glucose uptake; myocardial infarction; stem cells
ID ACID-BINDING PROTEIN; FATTY-ACID; COACTIVATOR PGC-1-ALPHA;
MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; 3T3-L1 ADIPOCYTES;
ENERGY-METABOLISM; MECHANISMS; TRANSPLANTATION; DISEASE
AB A constant provision of ATP is of necessity for cardiac contraction. As the heart progresses toward failure following a myocardial infarction (MI), it undergoes metabolic alterations that have the potential to compromise the ability to meet energetic demands. This study evaluated the efficacy of mesenchymal stem cell (MSC) transplantation into the infarcted heart to minimize impairments in the metabolic processes that contribute to energy provision. Seven and twenty-eight days following the MI and MSC transplantation, MSC administration minimized cardiac systolic dysfunction. Hyperinsulinemic-euglycemic clamps, coupled with 2-[C-14] deoxyglucose administration, were employed to assess systemic insulin sensitivity and tissue-specific, insulin-mediated glucose uptake 36 days following the MI in the conscious, unrestrained, C57BL/6 mouse. The improved systolic performance in MSC-treated mice was associated with a preservation of in vivo insulin-stimulated cardiac glucose uptake. Conserved glucose uptake in the heart was linked to the ability of the MSC treatment to diminish the decline in insulin signaling as assessed by Akt phosphorylation. The MSC treatment also sustained mitochondrial content, ADP-stimulated oxygen flux, and mitochondrial oxidative phosphorylation efficiency in the heart. Maintenance of mitochondrial function and density was accompanied by preserved peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, a master regulator of mitochondrial biogenesis. These studies provide insight into mechanisms of action that lead to an enhanced energetic state in the infarcted heart following MSC transplantation that may assist in energy provision and dampen cardiac dysfunction.
C1 [Hughey, Curtis C.; Shearer, Jane] Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada.
[James, Freyja D.; Bracy, Deanna P.; Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Ma, Lianli; Wang, Zhizhang; Wasserman, David H.; Rottman, Jeffrey N.] Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA.
[Rottman, Jeffrey N.] Vanderbilt Univ, Sch Med, Dept Med, Div Cardiovasc Med, Nashville, TN 37212 USA.
[Shearer, Jane] Univ Calgary, Fac Kinesiol, Calgary, AB T2N 1N4, Canada.
RP Hughey, CC (reprint author), Univ Calgary, KNB Rm 218,2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada.
EM cchughey@ucalgary.ca
FU Canadian Institutes of Health Research; Killam Trusts; MitoCanada;
National Institute of Diabetes and Digestive and Kidney Diseases
[DK-054902, DK-59637]
FX This work was supported by Canadian Institutes of Health Research (C. C.
Hughey, J. Shearer), the Killam Trusts (C. C. Hughey), MitoCanada (J.
Shearer), and National Institute of Diabetes and Digestive and Kidney
Diseases Grants DK-054902 (D. H. Wasserman) and DK-59637 (Vanderbilt
University Mouse Metabolic Phenotyping Center).
NR 48
TC 2
Z9 2
U1 1
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JAN
PY 2014
VL 306
IS 1
BP C19
EP C27
DI 10.1152/ajpcell.00156.2013
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 282SO
UT WOS:000329193700003
PM 24196528
ER
PT J
AU Cai, Y
Winn, ME
Zehmer, JK
Gillette, WK
Lubkowski, JT
Pilon, AL
Kimura, S
AF Cai, Yan
Winn, Melissa E.
Zehmer, John K.
Gillette, William K.
Lubkowski, Jacek T.
Pilon, Aprile L.
Kimura, Shioko
TI Preclinical evaluation of human secretoglobin 3A2 in mouse models of
lung development and fibrosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE SCGB; embryonic lung ex vivo organ culture; bleomycin-induced pulmonary
fibrosis; phospholipase A(2) inhibitory activity; drug candidate
treating lung diseases
ID RESPIRATORY-DISTRESS-SYNDROME; CELL 10-KDA PROTEIN; PULMONARY-FIBROSIS;
GROWTH-FACTOR; GENE-EXPRESSION; UTEROGLOBIN; MICE; BINDING;
INFLAMMATION; SUPERFAMILY
AB Secretoglobin (SCGB) 3A2 is a member of the SCGB gene superfamily of small secreted proteins, predominantly expressed in lung airways. We hypothesize that human SCGB3A2 may exhibit anti-inflammatory, growth factor, and antifibrotic activities and be of clinical utility. Recombinant human SCGB3A2 was expressed, purified, and biochemically characterized as a first step to its development as a therapeutic agent in clinical settings. Human SCGB3A2, as well as mouse SCGB3A2, readily formed a dimer in solution and exhibited novel phospholipase A2 inhibitory activity. This is the first demonstration of any quantitative biochemical measurement for the evaluation of SCGB3A2 protein. In the mouse as an experimental animal, human SCGB3A2 exhibited growth factor activity by promoting embryonic lung development in both ex vivo and in vivo systems and antifibrotic activity in the bleomycin-induced lung fibrosis model. The results suggested that human SCGB3A2 can function as a growth factor and an antifibrotic agent in humans. When SCGB3A2 was administered to pregnant female mice through the tail vein, the protein was detected in the dam's serum and lung, as well as the placenta, amniotic fluids, and embryonic lungs at 10 min postadministration, suggesting that SCGB3A2 readily crosses the placenta. The results warrant further development of recombinant SCGB3A2 as a therapeutic agent in treating patients suffering from lung diseases or preterm infants with respiratory distress.
C1 [Cai, Yan; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Winn, Melissa E.; Zehmer, John K.; Pilon, Aprile L.] Clarassance Inc, Rockville, MD USA.
[Gillette, William K.] Leidos Biomed Res Inc, Prot Express Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Lubkowski, Jacek T.] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21701 USA.
RP Kimura, S (reprint author), NIH, Bldg 37,Rm 3106,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kimuras@mail.nih.gov
RI Cai, Yan/P-4383-2015
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research [ZIABC010449]
FX This study was carried out under the CRADA (Corporate Research and
Development Agreement) between National Cancer Institute and
Clarassance, Inc. and funded in part by the Intramural Research Program
of the National Cancer Institute, Center for Cancer Research
(ZIABC010449).
NR 33
TC 5
Z9 5
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JAN
PY 2014
VL 306
IS 1
BP L10
EP L22
DI 10.1152/ajplung.00037.2013
PG 13
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 282SE
UT WOS:000329192400002
PM 24213919
ER
PT J
AU Sakamoto, K
Ueno, T
Kobayashi, N
Hara, S
Takashima, Y
Pastan, I
Matsusaka, T
Nagata, M
AF Sakamoto, Kazuo
Ueno, Toshiharu
Kobayashi, Namiko
Hara, Satoshi
Takashima, Yasutoshi
Pastan, Ira
Matsusaka, Taiji
Nagata, Michio
TI The direction and role of phenotypic transition between podocytes and
parietal epithelial cells in focal segmental glomerulosclerosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE focal segmental glomerulosclerosis; cellular FSGS; podocyte; parietal
epithelial cell; phenotypic transition
ID DE-NOVO EXPRESSION; GLOMERULAR PODOCYTES; NEPHROPATHY; SCLEROSIS;
PROTEINS; STRESS; INJURY; RATS; PAX2
AB Focal segmental glomerulosclerosis (FSGS) is a podocyte disease. Among the various histologies of FSGS, active epithelial changes, hyperplasia, as typically seen in the collapsing variant, indicates disease progression. Using a podocyte-specific injury model of FSGS carrying a genetic podocyte tag combined with double immunostaining by different sets of podocytes and parietal epithelial cell (PEC) markers [nestin/Pax8, Wilms' tumor- 1 (WT1)/claudin1, and podocalyxin/Pax2], we investigated the direction of epithelial phenotypic transition and its role in FSGS. FSGS mice showed progressive proteinuria and renal dysfunction often accompanied by epithelial hyperplasia, wherein 5-bromo-4-chloro- 3-indoyl beta-D-galactoside (X-gal)-positive podocyte-tagged cells were markedly decreased. The average numbers of double-positive cells in all sets of markers were significantly increased in the FSGS mice compared with the controls. In addition, the average numbers of double-positive cells for X-gal/Pax8, nestin/Pax8 and podocalyxin/Pax2 staining in the FSGS mice were comparable, whereas those of WT1/claudin1 were significantly increased. When we divided glomeruli from FSGS mice into those with FSGS lesions and those without, double-positive cells tended to be more closely associated with glomeruli without FSGS lesions compared with those with FSGS lesions. Moreover, the majority of double-positive cells appeared to be isolated and very rarely associated with FSGS lesions (1/1,997 glomeruli). This study is the first to show the incidence and localization of epithelial cells with phenotypical changes in FSGS using a genetic tag. The results suggest that the major direction of epithelial phenotypic transition in cellular FSGS is from podocytes to PECs and that these cells were less represented in the active lesions of FSGS.
C1 [Sakamoto, Kazuo; Ueno, Toshiharu; Kobayashi, Namiko; Hara, Satoshi; Takashima, Yasutoshi; Nagata, Michio] Univ Tsukuba, Fac Med, Ibaraki, Japan.
[Sakamoto, Kazuo] Iizuka Hosp, Dept Nephrol, Fukuoka, Japan.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Dept Internal Med, Isehara City, Kanagawa 2591100, Japan.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Nagata, M (reprint author), Univ Tsukuba, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058577, Japan.
EM nagatam@md.tsukuba.ac.jp
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center of Cancer Research; basic research
support program of the Japanese Society of Nephrology; Japan Society for
the Promotion of Science (KAKEN) [22590877]; Ministry of Health, Labor,
and Welfare of Japan
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center of
Cancer Research, and was also supported by the basic research support
program of the Japanese Society of Nephrology and by Grants-in-Aid for
Scientific Research of the Japan Society for the Promotion of Science
(KAKEN; research project no. 22590877) and Progressive Renal Disease
Research of the Ministry of Health, Labor, and Welfare of Japan.
NR 23
TC 23
Z9 23
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JAN
PY 2014
VL 306
IS 1
BP F98
EP F104
DI 10.1152/ajprenal.00228.2013
PG 7
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 282SL
UT WOS:000329193300012
PM 24154691
ER
PT J
AU Dickinson, D
AF Dickinson, Dwight
TI Zeroing In on Early Cognitive Development in Schizophrenia
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID INTELLIGENCE; IMPAIRMENT; CHILDHOOD; FLUID
C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Dickinson, D (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA.
EM dwight.dickinson@nih.gov
FU Intramural NIH HHS [Z99 MH999999, ZIA MH002712-19]
NR 19
TC 4
Z9 5
U1 1
U2 1
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JAN
PY 2014
VL 171
IS 1
BP 9
EP 12
DI 10.1176/appi.ajp.2013.13101303
PG 4
WC Psychiatry
SC Psychiatry
GA 286OO
UT WOS:000329478800003
PM 24399421
ER
PT J
AU Gorsi, B
Liu, F
Ma, X
Chico, TJA
Shrinivasan, A
Kramer, KL
Bridges, E
Monteiro, R
Harris, AL
Patient, R
Stringer, SE
AF Gorsi, Bushra
Liu, Feng
Ma, Xing
Chico, Timothy J. A.
Shrinivasan, Ashok
Kramer, Kenneth L.
Bridges, Esther
Monteiro, Rui
Harris, Adrian L.
Patient, Roger
Stringer, Sally E.
TI The heparan sulfate editing enzyme Sulf1 plays a novel role in zebrafish
VegfA mediated arterial venous identity
SO ANGIOGENESIS
LA English
DT Article
DE Angiogenesis; Arteries; VEGF; Glycocalyx; Sulf1
ID EMBRYONIC VASCULAR DEVELOPMENT; ENDOTHELIAL-GROWTH-FACTOR; IN-VIVO;
BRANCHING MORPHOGENESIS; REDUNDANT ROLES; ANGIOGENESIS; SOX18;
6-O-ENDOSULFATASES; DIFFERENTIATION; QSULF1
AB Arterial and venous specification is critical for establishing and maintaining a functioning vascular system, and defects in key arteriovenous signaling pathways including VEGF (vascular endothelial growth factor) lead to congenital arteriopathies. The activities of VEGF, are in part controlled by heparan sulfate (HS) proteoglycans, significant components of the endothelial glycocalyx. The level of 6-O sulfation on HS polysaccharide chains, that mediate the interaction between HS and VEGFA, is edited at the cell surface by the enzyme SULF1. We investigated the role of sulf1 in vascular development. In zebrafish sulf1 is expressed in the head and tail vasculature, corresponding spatially and temporally with vascular development. Targeted knockdown of sulf1 by antisense morpholinos resulted in severe vascular patterning and maturation defects. 93 % of sulf1 morphants show dysmorphogenesis in arterial development leading to occlusion of the distal aorta and lack of axial and cranial circulation. Co-injection of vegfa (165) mRNA rescued circulatory defects. While the genes affecting haematopoiesis are unchanged, expression of several arterial markers downstream of VegfA signalling such as notch and ephrinB2 are severely reduced in the dorsal aorta, with a concomitant increase in expression of the venous markers flt4 in the dorsal aorta of the morphants. Furthermore, in vitro, lack of SULF1 expression downregulates VEGFA-mediated arterial marker expression, confirming that Sulf1 mediates arterial specification by regulating VegfA(165) activity. This study provides the first in vivo evidence for the integral role of the endothelial glycocalyx in specifying arterial-venous identity, vascular patterning and arterial integrity, and will help to better understand congenital arteriopathies.
C1 [Gorsi, Bushra] Univ Manchester, Fac Med & Human Sci, Manchester M13 9NT, Lancs, England.
[Liu, Feng] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China.
[Ma, Xing] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Sheffield, S Yorkshire, England.
[Chico, Timothy J. A.] Univ Sheffield, MRC Ctr Dev & Biomed Genet, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England.
[Shrinivasan, Ashok; Kramer, Kenneth L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Bridges, Esther; Monteiro, Rui; Harris, Adrian L.; Patient, Roger] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
[Stringer, Sally E.] Univ Manchester, Fac Med & Human Sci, Inst Cardiovasc Sci, Manchester M13 9NT, Lancs, England.
RP Gorsi, B (reprint author), Univ Utah, Program Mol Med, Eccles Inst Human Genet, Dept Neurobiol & Anat, Bldg 533,Room 3160,15 North 2030 East, Salt Lake City, UT 84112 USA.
EM bgorsi@genetics.utah.edu; sally.stringer@manchester.ac.uk
RI Monteiro, Rui/J-2544-2013;
OI Monteiro, Rui/0000-0002-4223-8506; Harris, Adrian/0000-0003-1376-8409
FU University of Manchester Medical School strategic studentship; British
Heart Foundation; Diabetes UK; Medical Research Council; Cancer Research
UK
FX We would like to thank the BSU staff at the Universities of Manchester
and Oxford for taking care of the aquarium and the staff at the confocal
microscope core facilities. This work was funded by University of
Manchester Medical School strategic studentship, British Heart
Foundation, Diabetes UK, Medical Research Council and Cancer Research
UK. Conceived and designed the experiments: BG and SS. Performed the
experiments: BG, FL, EB, RM Analyzed the data: BG, FL, EB, SS.
Contributed reagents/materials/analysis tools: FL, AS, KLK, RP, AH, TC,
XM. Wrote the paper: BG and SS with input from RP and AH authors.
NR 50
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PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2014
VL 17
IS 1
BP 77
EP 91
DI 10.1007/s10456-013-9379-0
PG 15
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 283EJ
UT WOS:000329228000007
PM 23959107
ER
PT J
AU Davis, GE
Kim, DJ
Stratman, AN
Bowers, SLK
AF Davis, George E.
Kim, Dae Joong
Stratman, Amber N.
Bowers, Stephanie L. K.
TI Molecular control of capillary tube regression in 3D extracellular
matrices
SO ANGIOGENESIS
LA English
DT Meeting Abstract
C1 [Davis, George E.; Kim, Dae Joong; Bowers, Stephanie L. K.] Univ Missouri, Sch Med, Columbia, MO USA.
[Stratman, Amber N.] NICHD, NIH, Bethesda, MD USA.
NR 0
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U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2014
VL 17
IS 1
BP 281
EP 281
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 283EJ
UT WOS:000329228000044
ER
PT J
AU Xie, ZH
Ghosh, C
Awaki, S
Wisch, L
Nelson, C
Young, M
Parikh, S
Druey, KM
AF Xie Zhihui
Ghosh, Chandra
Awaki, Shoko
Wisch, Laura
Nelson, Celeste
Young, Michael
Parikh, Samir
Druey, Kirk M.
TI Phenotypic diversity of the systemic capillary leak syndrome (clarkson
disease)
SO ANGIOGENESIS
LA English
DT Meeting Abstract
C1 [Xie Zhihui; Awaki, Shoko; Wisch, Laura; Nelson, Celeste; Young, Michael; Druey, Kirk M.] NIH, Bethesda, MD 20892 USA.
[Ghosh, Chandra; Parikh, Samir] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ghosh, Chandra; Parikh, Samir] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
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U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2014
VL 17
IS 1
BP 302
EP 303
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 283EJ
UT WOS:000329228000124
ER
PT J
AU Sek, AC
Xie, ZH
Terai, K
Dudek, A
Druey, K
AF Sek, Albert C.
Xie Zhihui
Terai, Koaru
Dudek, Arkadiusz
Druey, Kirk
TI Role of endothelin receptor a in the systemic capillary leak syndrome
(SCLS)
SO ANGIOGENESIS
LA English
DT Meeting Abstract
C1 [Sek, Albert C.; Xie Zhihui; Druey, Kirk] NIH, Bethesda, MD 20892 USA.
[Terai, Koaru; Dudek, Arkadiusz] Univ Minnesota, Minneapolis, MN USA.
NR 0
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U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2014
VL 17
IS 1
BP 310
EP 310
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 283EJ
UT WOS:000329228000152
ER
PT J
AU Mukouyama, YS
James, J
Nalbandian, A
AF Mukouyama, Yoh-suke
James, Jennifer
Nalbandian, Ani
TI Regulation of TGF beta signaling by peripheral nerves influences skin
lymphangiogenesis
SO ANGIOGENESIS
LA English
DT Meeting Abstract
C1 [Mukouyama, Yoh-suke; James, Jennifer; Nalbandian, Ani] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2014
VL 17
IS 1
BP 312
EP 312
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 283EJ
UT WOS:000329228000159
ER
PT J
AU Outeda, P
Germino, GG
Watnick, TJ
AF Outeda, Patricia
Germino, Gregory G.
Watnick, Terry J.
TI Polycystin signaling is required for directed endothelial cell migration
and lymphatic development
SO ANGIOGENESIS
LA English
DT Meeting Abstract
C1 [Outeda, Patricia; Watnick, Terry J.] Univ Maryland, Baltimore, MD 21201 USA.
[Germino, Gregory G.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD JAN
PY 2014
VL 17
IS 1
BP 315
EP 315
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 283EJ
UT WOS:000329228000169
ER
PT J
AU Kulkarni, SR
Donepudi, AC
Xu, JL
Wei, W
Cheng, QQC
Driscoll, MV
Johnson, DA
Johnson, JA
Li, XL
Slitt, AL
AF Kulkarni, Supriya R.
Donepudi, Ajay C.
Xu, Jialin
Wei, Wei
Cheng, Qiuqiong C.
Driscoll, Maureen V.
Johnson, Delinda A.
Johnson, Jeffrey A.
Li, Xiaoling
Slitt, Angela L.
TI Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding
Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and
Human
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID ANTIOXIDANT RESPONSE ELEMENT; BILE-ACID; MOLECULAR-MECHANISMS;
CYCLIC-NUCLEOTIDES; LIVER; RESISTANCE; EXPRESSION; PATHWAY; SIRT1;
INDUCTION
AB Aims: The purpose of this study was to determine whether 3-5-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2-4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1-dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15-30.
C1 [Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Slitt, Angela L.] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA.
[Johnson, Delinda A.; Johnson, Jeffrey A.] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA.
[Li, Xiaoling] NIEHS, Lab Signal Transduct, Mammalian Aging Grp, Res Triangle Pk, NC 27709 USA.
RP Slitt, AL (reprint author), Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, 7 Greenhouse Rd, Kingston, RI 02881 USA.
EM aslitt@uri.edu
OI Kulkarni, Supriya/0000-0002-3146-0582
FU National Institutes of Health [5R01ES016042, 5K22ES013782]; Rhode Island
IDeA Network of Biomedical Research Excellence from the National Center
for Research Resources, National Institutes of Health [P20RR016457-10];
Rhode Island Foundation
FX The authors thank Drs. Joseph T. Rodgers and Pere Puigserver
(Dana-Farber Cancer Institute, Harvard Medical School) for sharing liver
tissue, Dr. Curtis D. Klaassen (University of Kansas Medical School) and
Dr. Jeff Chan (UC-Irvine) for sharing NRF2-null mice. We thank Dr.
Michael Goedken for histopathology consultation, as well as, Laura
Armstrong, Vijay More, Prajakta Shimpi, and Maneesha Paranjpe for
technical assistance. This work was supported by National Institutes of
Health [5R01ES016042], and, in part, by Rhode Island IDeA Network of
Biomedical Research Excellence [Award # P20RR016457-10] from the
National Center for Research Resources, National Institutes of Health,
National Institutes of Health [5K22ES013782], and the Rhode Island
Foundation.
NR 53
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U1 2
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD JAN 1
PY 2014
VL 20
IS 1
BP 15
EP 30
DI 10.1089/ars.2012.5082
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 284XU
UT WOS:000329356300002
PM 23725046
ER
PT J
AU Franco, R
Bortner, CD
Schmitz, I
Cidlowski, JA
AF Franco, Rodrigo
Bortner, Carl D.
Schmitz, Ingo
Cidlowski, John A.
TI Glutathione depletion regulates both extrinsic and intrinsic apoptotic
signaling cascades independent from multidrug resistance protein 1
SO APOPTOSIS
LA English
DT Article
DE Glutathione; Extrinsic; Intrinsic; MRP1; Multidrug resistance; MK571
ID MITOCHONDRIAL PERMEABILITY TRANSITION; REDUCED GLUTATHIONE; CASPASE-8
ACTIVATION; OXIDATIVE STRESS; LEUKEMIA-CELLS; IONIC HOMEOSTASIS; GSH
EXTRUSION; EFFLUX; TRANSPORT; FAS
AB Glutathione (GSH) depletion is an important hallmark of apoptosis. We previously demonstrated that GSH depletion, by its efflux, regulates apoptosis by modulation of executioner caspase activity. However, both the molecular identity of the GSH transporter(s) involved and the signaling cascades regulating GSH loss remain obscure. We sought to determine the role of multidrug resistance protein 1 (MRP1) in GSH depletion and its regulatory role on extrinsic and intrinsic pathways of apoptosis. In human lymphoma cells, GSH depletion was stimulated rather than inhibited by pharmacological blockage of MRP1 with MK571. GSH loss was dependent on initiator caspases 8 and 9 activity. Genetic knock-down (> 60 %) of MRP1 by stable transfection with short hairpin small interfering RNA significantly reduced MRP1 protein levels, which correlated directly with the loss of MRP1-mediated anion transport. However, GSH depletion and apoptosis induced by both extrinsic and intrinsic pathways were not affected by MRP1 knock-down. Interestingly, stimulation of GSH loss by MK571 also enhanced the initiator phase of apoptosis by stimulating initiator caspase 8 and 9 activity and pro-apoptotic BCL-2 interacting domain cleavage. Our results clearly show that caspase-dependent GSH loss and apoptosis are not mediated by MRP1 proteins and that GSH depletion stimulates the initiation phase of apoptosis in lymphoid cells.
C1 [Franco, Rodrigo] Univ Nebraska, Redox Biol Ctr, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA.
[Bortner, Carl D.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Schmitz, Ingo] Univ Magdeburg, Lab Syst Oriented Immunol & Inflammat Res, Inst Mol & Clin Immunol, D-39106 Magdeburg, Germany.
[Schmitz, Ingo] Helmholtz Ctr Infect Res, Div Immune Control, D-38124 Braunschweig, Germany.
RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
RI Franco, Rodrigo/D-9470-2013
OI Franco, Rodrigo/0000-0003-3241-8615
FU Intramural Research Program of the NIH/National Institute of
Environmental Health Sciences [1Z01ES090079]; Centers of Biomedical
Research Excellence (COBRE) Grant (Franco) [P20RR17675]
FX This work was supported by the Intramural Research Program of the
NIH/National Institute of Environmental Health Sciences 1Z01ES090079
(Cidlowski and Bortner), the P20RR17675 Centers of Biomedical Research
Excellence (COBRE) Grant (Franco).
NR 77
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U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
EI 1573-675X
J9 APOPTOSIS
JI Apoptosis
PD JAN
PY 2014
VL 19
IS 1
BP 117
EP 134
DI 10.1007/s10495-013-0900-0
PG 18
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 284CP
UT WOS:000329294000009
PM 24146141
ER
PT J
AU Duarte, RF
Greinix, H
Rabin, B
Mitchell, SA
Basak, G
Wolff, D
Madrigal, JA
Pavletic, SZ
Lee, SJ
AF Duarte, R. F.
Greinix, H.
Rabin, B.
Mitchell, S. A.
Basak, G.
Wolff, D.
Madrigal, J. A.
Pavletic, S. Z.
Lee, S. J.
TI Uptake and use of recommendations for the diagnosis, severity scoring
and management of chronic GVHD: an international survey of the EBMT-NCI
Chronic GVHD Task Force
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE chronic GVHD; allogeneic hematopoietic cell transplantation; survey;
uptake; implementation; recommendations
ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING
GROUP-REPORT; CLINICAL-TRIALS; CELL TRANSPLANTATION; CRITERIA; ORGAN
AB In 2005, the National Institutes of Health (NIH) consensus conference published a series of papers recommending methods to improve the conduct of clinical trials in chronic GVHD. Although the NIH recommendations were primarily aimed at strengthening research, several papers addressed issues relevant for clinical practice, particularly diagnosis, severity scoring, and ancillary and supportive care practices. We conducted an international survey to assess the uptake of these recommendations, identify barriers to greater use and document the use and perceived effectiveness of available treatments. The response rate for the American survey of 1387 practitioners was 21.8%, and it was 24.6% for 407 centers surveyed in Europe, Asia, Australia and Africa. Most respondents were familiar with the NIH consensus recommendations (94-96%) and used them in practice. Multiple barriers to greater use were reported. Besides lack of time (55-62%), unfamiliarity with the recommendations, scarcity of evidence supporting the impact of recommendations on outcomes, insufficient training/experience in chronic GVHD management and inaccessibility of subspecialists were also endorsed. Systemic corticosteroids were reported to be the most effective treatment for chronic GVHD, but many others were perceived to have moderate or great success. Therapeutic management of steroid-refractory chronic GVHD was identified as the highest priority for research.
C1 [Duarte, R. F.] Hosp Duran I Reynals, Catalan Inst Oncol, Dept Hematol, Barcelona, Spain.
[Greinix, H.] Med Univ Vienna, Dept Internal Med 1, Vienna, Austria.
[Rabin, B.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA.
[Mitchell, S. A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Basak, G.] Med Univ Warsaw, Dept Hematol Oncol & Internal Med, Warsaw, Poland.
[Wolff, D.] Univ Regensburg, Dept Internal Med 3, D-93053 Regensburg, Germany.
[Madrigal, J. A.] Royal Free Hosp, Anthony Nolan Res Inst, London NW3 2QG, England.
[Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Lee, S. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North,D5-290, Seattle, WA 98109 USA.
EM sjlee@fhcrc.org
FU The Center for Global Health; Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX We thank all the participating practitioners and centers, CIBMTR for
providing contact information for the American survey and the EBMT
administrative office for their help with survey distribution to EBMT
centers. The Center for Global Health provided support for the initial
meeting of the EBMT-NCI Chronic GVHD Task Force. This work was in part
supported by the Center for Cancer Research, the intramural program of
the National Cancer Institute, National Institutes of Health. The
Chronic GVHD Consortium (U54 CA163438) is a part of the National
Institutes of Health (NIH) Rare Diseases Clinical Research Network
(RDCRN), supported through collaboration between the NIH Office of Rare
Diseases Research (ORDR) at the National Center for Advancing
Translational Science (NCATS), and the National Cancer Institute. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 20
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JAN
PY 2014
VL 49
IS 1
BP 49
EP 54
DI 10.1038/bmt.2013.129
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 286CN
UT WOS:000329442200009
PM 23955633
ER
PT J
AU Bassim, CW
Fassil, H
Mays, JW
Edwards, D
Baird, K
Steinberg, SM
Williams, KM
Cowen, EW
Mitchell, SA
Cole, K
Taylor, T
Avila, D
Zhang, D
Pulanic, D
Grkovic, L
Fowler, D
Gress, RE
Pavletic, SZ
AF Bassim, C. W.
Fassil, H.
Mays, J. W.
Edwards, D.
Baird, K.
Steinberg, S. M.
Williams, K. M.
Cowen, E. W.
Mitchell, S. A.
Cole, K.
Taylor, T.
Avila, D.
Zhang, D.
Pulanic, D.
Grkovic, L.
Fowler, D.
Gress, R. E.
Pavletic, S. Z.
TI Validation of the National Institutes of Health chronic GVHD Oral
Mucosal Score using component-specific measures
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE oral cGVHD; chronic graft-versus-host disease; validation
ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; STEM-CELL
TRANSPLANTATION; WORKING GROUP-REPORT; THERAPEUTIC RESPONSE;
CLINICAL-TRIALS; CANCER; SCALE; CGVHD; CRITERIA
AB Oral chronic GVHD (cGVHD) is a common, late complication of alloSCT that is associated with significant patient morbidity. The NIH Oral Mucosal Score (NIH OMS) was developed to assess oral cGVHD therapeutic response, but has not been fully validated. This study's purpose was to conduct a rigorous construct validity and internal consistency analysis of this score and its components (erythema, lichenoid, ulcers, mucoceles) using established measures of oral pain, oral function, oral-related quality-of-life, nutrition and laboratory parameters in 198 patients with cGVHD. The construct validity of the NIH OMS was supported: a moderate correlation was observed between NIH OMS and mouth pain (rho = 0.43), while a weaker correlation was observed with low albumin (rho = -0.26). Total NIH OMS, erythema and lichenoid components were associated with malnutrition, oral pain and impaired oral QOL, while ulcers were only associated with oral pain. No associations were found between mucoceles and any indicator evaluated, including salivary function or xerostomia. Kappa determined between scale components was low overall (all <= 0.35), supporting a conclusion that each component measures a distinct manifestation of oral cGVHD. This study supports the use of the NIH OMS and its components (erythema, lichenoid and ulcerations) to measure clinician-reported severity of oral cGVHD.
C1 [Bassim, C. W.; Mays, J. W.; Edwards, D.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Fassil, H.; Williams, K. M.; Cole, K.; Taylor, T.; Avila, D.; Pulanic, D.; Grkovic, L.; Fowler, D.; Gress, R. E.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Fassil, H.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA.
[Baird, K.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, S. M.; Zhang, D.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Cowen, E. W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Mitchell, S. A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Pulanic, D.; Grkovic, L.] Clin Hosp Ctr Zagreb, Dept Internal Med, Div Hematol, Zagreb, Croatia.
RP Bassim, CW (reprint author), Natl Inst Dent & Craniofacial Res, Clin Res Ctr, NIH, Bldg 10,Room 1N-117, Bethesda, MD 20892 USA.
EM carol.bassim@nih.gov
FU NIH; Pfizer Inc.; National Cancer Institute, Center for Cancer Research,
National Institute of Health
FX H Fassil's research year was made possible through the Clinical Research
Training Program, a public-private partnership supported jointly by the
NIH and Pfizer Inc., and by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, National
Institute of Health.
NR 29
TC 6
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U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JAN
PY 2014
VL 49
IS 1
BP 116
EP 121
DI 10.1038/bmt.2013.137
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 286CN
UT WOS:000329442200019
PM 23995099
ER
PT J
AU Dan, T
Hewitt, SM
Ohri, N
Ly, D
Soule, BP
Smith, SL
Matsuda, K
Council, C
Shankavaram, U
Lippman, ME
Mitchell, JB
Camphausen, K
Simone, NL
AF Dan, T.
Hewitt, S. M.
Ohri, N.
Ly, D.
Soule, B. P.
Smith, S. L.
Matsuda, K.
Council, C.
Shankavaram, U.
Lippman, M. E.
Mitchell, J. B.
Camphausen, K.
Simone, N. L.
TI CD44 is prognostic for overall survival in the NCI randomized trial on
breast conservation with 25 year follow-up
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Breast conservation; CD44; Biomarker; Randomized trial
ID NEOADJUVANT CHEMOTHERAPY RESPONSE; CANCER STEM-CELLS; NODE METASTASIS;
TUMOR-MARKERS; EXPRESSION; HYALURONAN; CARCINOMA; CD44(+)/CD24(-/LOW);
PHARMACOKINETICS; DIFFERENTIATION
AB CD44 is a transmembrane glycoprotein involved in numerous cellular functions, including cell adhesion and extracellular matrix interactions. It is known to be functionally diverse, with alternative splice variants increasingly implicated as a marker for tumor-initiating stem cells associated with poor prognosis. Here, we evaluate CD44 as a potential marker of long-term breast cancer outcomes. Tissue specimens from patients treated on the National Cancer Institute 79-C-0111 randomized trial of breast conservation versus mastectomy between 1979 and 1987 were collected, and immunohistochemistry was performed using the standard isoform of CD44. Specimens were correlated with patient characteristics and outcomes. Survival analysis was performed using the log rank test. Fifty-one patients had evaluable tumor sections and available long-term clinical follow up data at a median follow up of 25.7 years. Significant predictors of OS were tumor size (median OFS 25.4 years for a parts per thousand currency sign2 cm vs. 7.5 years for > 2 cm, p = 0.001), nodal status (median OS 17.2 years for node-negative patients vs. 6.7 years for node positive patients, p = 0.017), and CD44 expression (median OS 18.9 years for CD44 positive patients vs. 8.6 years for CD44 negative patients, p = 0.049). There was a trend toward increased PFS for patients with CD44 positive tumors (median PFS 17.9 vs. 4.3 years, p = 0.17), but this did not reach statistical significance. These findings illustrate the potential utility of CD44 as a prognostic marker for early stage breast cancer. Subgroup analysis in patients with lymph node involvement revealed CD44 positivity to be most strongly associated with increased survival, suggesting a potential role of CD44 in decision making for axillary management. As there is increasing interest in CD44 as a therapeutic target in ongoing clinical trials, the results of this study suggest additional investigation regarding the role CD44 in breast cancer is warranted.
C1 [Dan, T.; Ohri, N.; Simone, N. L.] Thomas Jefferson Univ, Dept Radiat Oncol, Bodine Ctr Canc Treatment, Kimmel Canc Ctr,Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Hewitt, S. M.; Matsuda, K.] NCI, Pathol Branch, Bethesda, MD 20892 USA.
[Ly, D.; Smith, S. L.; Council, C.; Shankavaram, U.; Camphausen, K.; Simone, N. L.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Soule, B. P.; Mitchell, J. B.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
[Lippman, M. E.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Simone, NL (reprint author), Thomas Jefferson Univ, Dept Radiat Oncol, Bodine Ctr Canc Treatment, Kimmel Canc Ctr,Jefferson Med Coll, 111 S 11th St G-301G, Philadelphia, PA 19107 USA.
EM nicole.simone@jeffersonhospital.org
OI Dan, Tu/0000-0003-1154-0507; Hewitt, Stephen/0000-0001-8283-1788
FU NIH; Kimmel Cancer Center's NCI Cancer Center [P30 CA56036]
FX Research support was in part through the Intramural Research Program of
the NIH and also in part by the Kimmel Cancer Center's NCI Cancer Center
Support Grant P30 CA56036.
NR 55
TC 7
Z9 7
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JAN
PY 2014
VL 143
IS 1
BP 11
EP 18
DI 10.1007/s10549-013-2758-9
PG 8
WC Oncology
SC Oncology
GA 284DE
UT WOS:000329295500002
PM 24276281
ER
PT J
AU Horne, HN
Sherman, ME
Garcia-Closas, M
Pharoah, PD
Blows, FM
Yang, XHR
Hewitt, SM
Conway, CM
Lissowska, J
Brinton, LA
Prokunina-Olsson, L
Dawson, SJ
Caldas, C
Easton, DF
Chanock, SJ
Figueroa, JD
AF Horne, Hisani N.
Sherman, Mark E.
Garcia-Closas, Montserrat
Pharoah, Paul D.
Blows, Fiona M.
Yang, Xiaohong R.
Hewitt, Stephen M.
Conway, Catherine M.
Lissowska, Jolanta
Brinton, Louise A.
Prokunina-Olsson, Ludmila
Dawson, Sarah-Jane
Caldas, Carlos
Easton, Douglas F.
Chanock, Stephen J.
Figueroa, Jonine D.
TI Breast cancer susceptibility risk associations and heterogeneity by
E-cadherin tumor tissue expression
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE E-cadherin; Single nucleotide polymorphism (SNP); Genetics of risk
ID GENOME-WIDE ASSOCIATION; PROGNOSTIC-SIGNIFICANCE; LOBULAR CARCINOMA;
14Q24.1 RAD51L1; VARIANTS; MARKERS; TRANSITION; CONSORTIUM; SUBTYPES;
1P11.2
AB E-cadherin is involved in cell-cell adhesion and epithelial-to-mesenchymal transitions. In cancers, loss or inactivation of E-cadherin is associated with epithelial cell proliferation and invasion. Here, we sought to determine, if risk associations for 18 breast cancer susceptibility single nucleotide polymorphisms (SNPs) differed by E-cadherin tumor tissue expression in the Polish Breast Cancer Study (PBCS), using data on 1,347 invasive breast cancer cases and 2,366 controls. E-cadherin expression (low/high) was assessed using immunohistochemical staining of tumor tissue microarrays. Replication data on 2,006 cases and 6,714 controls from the Study of Epidemiology and Risk Factors in Cancer Heredity was used to follow-up promising findings from PBCS. In PBCS, we found the rs11249433 SNP at the 1p11.2 locus to be more strongly associated with risk of E-cadherin low tumors (OR = 1.30, 95 % CI = 1.08-1.56) than with E-cadherin high tumors [OR = 1.06, 95 % CI = 0.95-1.18; case-only p-heterogeneity (p-het) = 0.05]. Findings in PBCS for rs11249433 were replicated in SEARCH. Combined analyses of the two datasets for SNP rs11249433 revealed significant heterogeneity by E-cadherin expression (combined case-only p-het = 0.004). Further, among carriers of rs11249433, the highest risk was seen for E-cadherin low tumors that were ER-positive and of lobular histology. Our results in two independent data sets suggest that rs11249433, which is located between the NOTCH2 and FCGR1B genes within the 1p11.2 locus, is more strongly associated with risk of breast tumors with low or absent E-cadherin expression, and suggest that evaluation of E-cadherin tumor tissue expression may be useful in clarifying breast cancer risk factor associations.
C1 [Horne, Hisani N.; Yang, Xiaohong R.; Brinton, Louise A.; Prokunina-Olsson, Ludmila; Chanock, Stephen J.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Horne, Hisani N.] NCI, NIH, DCEG, HREB, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
[Garcia-Closas, Montserrat] Breast Canc Breakthrough Ctr, London, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Sect Epidemiol & Genet, Sutton, Surrey, England.
[Pharoah, Paul D.; Blows, Fiona M.; Dawson, Sarah-Jane; Caldas, Carlos; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Pharoah, Paul D.; Blows, Fiona M.; Dawson, Sarah-Jane; Caldas, Carlos; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Hewitt, Stephen M.; Conway, Catherine M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
RP Horne, HN (reprint author), NCI, NIH, DCEG, HREB, 9609 Med Ctr Dr,Rm 7E234 MSC 7234, Bethesda, MD 20892 USA.
EM hisani.horne@nih.gov
RI Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Dawson, Sarah-Jane/0000-0002-8276-0374;
Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Hewitt,
Stephen/0000-0001-8283-1788; Lissowska, Jolanta/0000-0003-2695-5799
FU Intramural Research Programs of the Division of Cancer Epidemiology and
Genetics; Center for Cancer Research of the National Cancer Institute;
Breakthrough Breast Cancer Centre; Institute of Cancer Research, London,
UK; NHS
FX This research was supported by the Intramural Research Programs of the
Division of Cancer Epidemiology and Genetics and Center for Cancer
Research of the National Cancer Institute. M. Garcias-Closas is funded
by the Breakthrough Breast Cancer Centre and the Institute of Cancer
Research, London, UK. We acknowledge NHS funding to the Royal
Marsden/ICR NIHR Biomedical Research Centre.
NR 28
TC 7
Z9 7
U1 0
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JAN
PY 2014
VL 143
IS 1
BP 181
EP 187
DI 10.1007/s10549-013-2771-z
PG 7
WC Oncology
SC Oncology
GA 284DE
UT WOS:000329295500018
PM 24292867
ER
PT J
AU Larkin, KL
Saboo, US
Comer, GM
Forooghian, F
Mackensen, F
Merrill, P
Sen, HN
Singh, A
Essex, RW
Lake, S
Lim, LL
Vasconcelos-Santos, DV
Foster, CS
Wilson, DJ
Smith, JR
AF Larkin, Kelly L.
Saboo, Ujwala S.
Comer, Grant M.
Forooghian, Farzin
Mackensen, Friederike
Merrill, Pauline
Sen, H. Nida
Singh, Arun
Essex, Rohan W.
Lake, Stewart
Lim, Lyndell L.
Vasconcelos-Santos, Daniel V.
Foster, C. Stephen
Wilson, David J.
Smith, Justine R.
TI Use of intravitreal rituximab for treatment of vitreoretinal lymphoma
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PRIMARY INTRAOCULAR LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; PRIMARY CNS
LYMPHOMA; COLLABORATIVE GROUP-REPORT; B-CELLS; METHOTREXATE; OUTCOMES;
INVOLVEMENT; INJECTIONS; FEATURES
AB Aim Vitreoretinal lymphoma is a diffuse large B cell non-Hodgkin lymphoma. Targeting malignant cells with rituximab is being used increasingly as local chemotherapy, but information on this treatment is scant. We aimed to describe current therapeutic approaches, as well as responses to and complications of, intravitreal rituximab in patients with vitreoretinal lymphoma.
Methods Clinical data were collected in a standardised manner retrospectively on patients with vitreoretinal lymphoma treated with intravitreal rituximab.
Results 48 eyes (34 patients) with vitreoretinal lymphoma were treated with a median of 3.5 intravitreal injections of rituximab (1 mg/0.1 mL) for new diagnosis (68.8%), progressive disease (29.9%) and maintenance therapy (2.1%). Intravitreal rituximab +/- methotrexate was the sole treatment in 19 eyes (39.6%). 31 eyes (64.6%) eyes achieved complete remission, after a median of 3 injections; 7 of these eyes developed recurrent disease. 11 eyes (22.9%) achieved partial remission. Although rituximab may have contributed to complications reported in 12 eyes (25.0%), a 2-line loss of Snellen visual acuity occurred in only 2 of those eyes (4.2%).
Conclusions Approaches in rituximab-based intravitreal chemotherapy vary widely, but our findings suggest that this treatment may be safe and effective in inducing remission in a majority of eyes with vitreoretinal lymphoma.
C1 [Larkin, Kelly L.; Wilson, David J.; Smith, Justine R.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
[Saboo, Ujwala S.; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Saboo, Ujwala S.; Foster, C. Stephen] Ocular Immunol & Uveitis Fdn, Cambridge, MA USA.
[Comer, Grant M.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA.
[Forooghian, Farzin] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada.
[Mackensen, Friederike] Univ Klinikum Heidelberg, Dept Ophthalmol, Interdisciplinary Uveitis Ctr, Heidelberg, Germany.
[Merrill, Pauline] Rush Univ, Dept Ophthalmol, Chicago, IL 60612 USA.
[Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Singh, Arun] Cleveland Clin, Cleveland, OH 44106 USA.
[Essex, Rohan W.] Australian Natl Univ, Dept Ophthalmol, Canberra, ACT, Australia.
[Lake, Stewart; Smith, Justine R.] Flinders Univ S Australia, Adelaide, SA 5001, Australia.
[Lim, Lyndell L.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Vasconcelos-Santos, Daniel V.] Univ Fed Minas Gerais, Dept Uveitis & Ophthalm Pathol, Belo Horizonte, MG, Brazil.
[Foster, C. Stephen] Harvard Univ, Dept Ophthalmol, Cambridge, MA 02138 USA.
RP Smith, JR (reprint author), Flinders Univ S Australia, Sch Med, Flinders Med Ctr, Room 4E-431,Flinders Dr, Bedford Pk, SA 5042, Australia.
EM justine.smith@flinders.edu.au
OI Lim, Lyndell/0000-0003-2491-685X
FU Research to Prevent Blindness
FX This work was supported in part by Research to Prevent Blindness
(Unrestricted Grant to: Casey Eye Institute, Oregon Health & Science
University).
NR 30
TC 10
Z9 11
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JAN
PY 2014
VL 98
IS 1
BP 99
EP 103
DI 10.1136/bjophthalmol-2013-304043
PG 5
WC Ophthalmology
SC Ophthalmology
GA 269MX
UT WOS:000328246500020
PM 24158837
ER
PT J
AU Hecht, SS
Szabo, E
AF Hecht, Stephen S.
Szabo, Eva
TI Fifty Years of Tobacco Carcinogenesis Research: From Mechanisms to Early
Detection and Prevention of Lung Cancer
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NICOTINE METABOLITE RATIO; RISK PREDICTION MODEL; SUSCEPTIBILITY LOCUS;
CIGARETTE-SMOKING; POLICY STATEMENT; GENE-EXPRESSION; SCREENING CT;
SMOKERS; TRIAL; BIOMARKERS
AB The recognition of the link between cigarette smoking and lung cancer in the 1964 Surgeon General's Report initiated definitive and comprehensive research on the identification of carcinogens in tobacco products and the relevant mechanisms of carcinogenesis. The resultant comprehensive data clearly illustrate established pathways of cancer induction involving carcinogen exposure, metabolic activation, DNA adduct formation, and consequent mutation of critical genes along with the exacerbating influences of inflammation, cocarcinogenesis, and tumor promotion. This mechanistic understanding has provided a framework for the regulation of tobacco products and for the development of relevant tobacco carcinogen and toxicant biomarkers that can be applied in cancer prevention. Simultaneously, the recognition of the link between smoking and lung cancer paved the way for two additional critical approaches to cancer prevention that are discussed here: detection of lung cancer at an early, curable stage, and chemoprevention of lung cancer. Recent successes in more precisely identifying at-risk populations and in decreasing lung cancer mortality with helical computed tomography screening are notable, and progress in chemoprevention continues, although challenges with respect to bringing these approaches to the general population exist. Collectively, research performed since the 1964 Report demonstrates unequivocally that the majority of deaths from lung cancer are preventable.
C1 [Hecht, Stephen S.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN 55455 USA.
[Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Hecht, SS (reprint author), Univ Minnesota, Mason Canc Ctr, 2231 6th St Southeast,Room 2-148 CCRB, Minneapolis, MN 55455 USA.
EM hecht002@umn.edu; szaboe@mail.nih.gov
OI Hecht, Stephen/0000-0001-7228-1356
FU [CA-81301]; [CA-92025]
FX This work was supported by CA-81301 and CA-92025 (to S.S. Hecht).
NR 52
TC 13
Z9 13
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JAN
PY 2014
VL 7
IS 1
BP 1
EP 8
DI 10.1158/1940-6207.CAPR-13-0371
PG 8
WC Oncology
SC Oncology
GA 285YR
UT WOS:000329431500001
PM 24403288
ER
PT J
AU Klepin, HD
Geiger, AM
Bandos, H
Costantino, JP
Rapp, SR
Sink, KM
Lawrence, JA
Atkinson, HH
Espeland, MA
AF Klepin, Heidi D.
Geiger, Ann M.
Bandos, Hanna
Costantino, Joseph P.
Rapp, Stephen R.
Sink, Kaycee M.
Lawrence, Julia A.
Atkinson, Hal H.
Espeland, Mark A.
TI Cognitive Factors Associated with Adherence to Oral Antiestrogen
Therapy: Results from the Cognition in the Study of Tamoxifen and
Raloxifene (Co-STAR) Study
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID POSITIVE BREAST-CANCER; MEDICATION ADHERENCE; HORMONAL-THERAPY; OLDER
WOMEN; ALZHEIMERS-DISEASE; ADJUVANT TAMOXIFEN; UNITED-STATES;
NONADHERENCE; DISCONTINUATION; IMPAIRMENT
AB Little is known about the cognitive factors associated with adherence to antiestrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral antiestrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled nondemented participants >= 65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol >= 80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2 +/- 4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were nonadherent. In adjusted analyses, the odds of nonadherence were lower for those with better scores on verbal memory [OR (95% confidence interval): 0.75 (0.62-0.92)]. Larger relative deficits in verbal memory compared with verbal fluency were also associated with nonadherence [1.28 (1.08-1.51)]. Among nondemented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence.
C1 [Klepin, Heidi D.; Rapp, Stephen R.; Sink, Kaycee M.; Lawrence, Julia A.; Atkinson, Hal H.; Espeland, Mark A.] Wake Forest Sch Med, Winston Salem, NC USA.
[Geiger, Ann M.] NCI, Rockville, MD USA.
[Bandos, Hanna; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Bandos, Hanna; Costantino, Joseph P.] Natl Surg Adjuvant Breast & Bowel Project NSABP B, Pittsburgh, PA USA.
RP Klepin, HD (reprint author), Wake Forest Baptist Hlth, Sect Hematol & Oncol, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM hklepin@wakehealth.edu
FU Public Health Service grants from the National Cancer Institute, NIH
[U10-CA-37377, U10-CA-69974, U10CA-12027, U10CA-69651]; Department of
Health and Human Services; AstraZeneca Pharmaceuticals; Eli Lilly and
Co; National Institute on Aging [NO1-AG-2106]; Intramural Research
Program, NIA, NIH; NIA, NIH; Wake Forest University Claude D. Pepper
Older Americans Independence Center [P30 AG-021332]; Atlantic
Philanthropies; American Society of Hematology; John A. Hartford
Foundation; Association of Specialty Professors; Paul Beeson Career
Development Award in Aging Research [K23AG038361]; NIA; AFAR;
Gabrielle's Angel Foundation for Cancer Research
FX STAR was supported by Public Health Service grants U10-CA-37377,
U10-CA-69974, U10CA-12027, and U10CA-69651 from the National Cancer
Institute, NIH, Department of Health and Human Services, AstraZeneca
Pharmaceuticals, and Eli Lilly and Co (to J. Costantino). Co-STAR was
supported by the National Institute on Aging, NO1-AG-2106, and in part
by the Intramural Research Program, NIA, NIH (M. Espeland, H. Klepin).
Dr. Klepin was also funded in part by the Intramural Research Program,
NIA, NIH, the Wake Forest University Claude D. Pepper Older Americans
Independence Center (P30 AG-021332), Atlantic Philanthropies, American
Society of Hematology, John A. Hartford Foundation and Association of
Specialty Professors. Current support includes a Paul Beeson Career
Development Award in Aging Research (K23AG038361; supported by NIA,
AFAR, The John A. Hartford Foundation, and The Atlantic Philanthropies)
and The Gabrielle's Angel Foundation for Cancer Research (H. Klepin).
NR 35
TC 9
Z9 9
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JAN
PY 2014
VL 7
IS 1
BP 161
EP 168
DI 10.1158/1940-6207.CAPR-13-0165
PG 8
WC Oncology
SC Oncology
GA 285YR
UT WOS:000329431500017
PM 24253314
ER
PT J
AU Kitahara, CM
Gamborg, M
de Gonzalez, AB
Sorensen, TIA
Baker, JL
AF Kitahara, Cari M.
Gamborg, Michael
de Gonzalez, Amy Berrington
Sorensen, Thorkild I. A.
Baker, Jennifer L.
TI Childhood Height and Body Mass Index Were Associated with Risk of Adult
Thyroid Cancer in a Large Cohort Study
SO CANCER RESEARCH
LA English
DT Article
ID ANTHROPOMETRIC FACTORS; INCREASING INCIDENCE; PHYSICAL-ACTIVITY; POOLED
ANALYSIS; SECULAR TRENDS; OBESITY; GROWTH; POPULATION; OVERWEIGHT;
PATTERNS
AB Taller stature and obesity in adulthood have been consistently associated with an increased risk of thyroid cancer, but few studies have investigated the role of childhood body size. Using data from a large prospective cohort, we examined associations for height and body mass index (BMI) at ages 7 to 13 years with risk of thyroid cancer in later life. The study population included 321,085 children from the Copenhagen School Health Records Register, born between 1930 and 1989 in Copenhagen, Denmark, with measurements of height and weight from 7 to 13 years of age. These data were linked with the Danish Cancer Registry to identify incident thyroid cancer cases (1968-2010). Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for age- and sex-specific height and BMI SD scores (SDS) using proportional hazards models stratified by birth cohort and sex. During follow-up (median = 38.6 years), 171 women and 64 men were diagnosed with thyroid cancer. Both height and BMI were positively associated with thyroid cancer risk, and these associations were similar by age at measurement. Using age 10 as an example, HRs per 1 unit increase in SDS for height (similar to 6-7 cm) and BMI (similar to 1.5-2 kg/m(2)) were 1.22 (95% CI, 1.07-1.40) and 1.15 (95% CI, 1.00-1.34), respectively. These results, together with the relatively young ages at which thyroid cancers are diagnosed compared with other malignancies, suggest a potential link between early-life factors related to growth and body weight and thyroid carcinogenesis. (C)2013 AACR.
C1 [Kitahara, Cari M.; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Gamborg, Michael; Sorensen, Thorkild I. A.; Baker, Jennifer L.] Inst Prevent Med, Frederiksberg, Denmark.
[Gamborg, Michael; Sorensen, Thorkild I. A.; Baker, Jennifer L.] Bispebjerg Hosp, DK-2400 Copenhagen, Denmark.
[Gamborg, Michael; Sorensen, Thorkild I. A.; Baker, Jennifer L.] Frederiksberg Univ Hosp, Copenhagen, Denmark.
[Sorensen, Thorkild I. A.; Baker, Jennifer L.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
RP Baker, JL (reprint author), Inst Prevent Med, Nordre Fasanvej 57, Frederiksberg, Denmark.
EM jennifer.lyn.baker@regionh.dk
RI Baker, Jennifer/F-1917-2010; Kitahara, Cari/R-8267-2016
OI Baker, Jennifer/0000-0002-9649-6615;
FU Intramural Research Program of the National Cancer Institute; European
Research Council under European Union; ERC [281418]; NIH
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute, NIH and by funding from the European
Research Council under the European Union's Seventh Framework Programme
(FP/2007-2013), ERC Grant Agreement no. 281418, childgrowth2-cancer
(J.L. Baker).
NR 42
TC 17
Z9 19
U1 0
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 1
PY 2014
VL 74
IS 1
BP 235
EP 242
DI 10.1158/0008-5472.CAN-13-2228
PG 8
WC Oncology
SC Oncology
GA 284DZ
UT WOS:000329297600023
PM 24247722
ER
PT J
AU Li, HT
Zhu, F
Chen, HY
Cheng, KW
Zykova, T
Oi, N
Lubet, RA
Bode, AM
Wang, MF
Dong, ZG
AF Li, Haitao
Zhu, Feng
Chen, Hanyong
Cheng, Ka Wing
Zykova, Tatyana
Oi, Naomi
Lubet, Ronald A.
Bode, Ann M.
Wang, Mingfu
Dong, Zigang
TI 6-C-(E-phenylethenyl)-Naringenin Suppresses Colorectal Cancer Growth by
Inhibiting Cyclooxygenase-1
SO CANCER RESEARCH
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ADENOMATOUS POLYPOSIS; INTESTINAL
POLYPOSIS; RANDOMIZED-TRIAL; ASPIRIN; CHEMOPREVENTION; PREVENTION;
MOUSE; COX-2; EXPRESSION
AB Recent clinical trials raised concerns regarding the cardiovascular toxicity of selective cyclooxygenase-2 (COX-2) inhibitors and cyclooxygenase-1 (COX-1) is now being reconsidered as a target for chemoprevention. Our aims were to determine whether selective COX-1 inhibition could delay or prevent cancer development and also clarify the underlying mechanisms. Data clearly showed that COX-1 was required for maintenance of malignant characteristics of colon cancer cells or tumor promoter-induced transformation of preneoplastic cells. We also successfully applied a ligand-docking computational method to identify a novel selective COX-1 inhibitor, 6-C-(E-phenylethenyl)-naringenin (designated herein as 6CEPN). 6CEPN could bind to COX-1 and specifically inhibited its activity both in vitro and ex vivo. In colorectal cancer cells, it potently suppressed anchorage-independent growth by inhibiting COX-1 activity. 6CEPN also effectively suppressed tumor growth in a 28-day colon cancer xenograft model without any obvious systemic toxicity. Taken together, COX-1 plays a critical role in human colorectal carcinogenesis, and this specific COX-1 inhibitor merits further investigation as a potential preventive agent against colorectal cancer. (C)2013 AACR.
C1 [Li, Haitao; Zhu, Feng; Chen, Hanyong; Zykova, Tatyana; Oi, Naomi; Bode, Ann M.; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55009 USA.
[Lubet, Ronald A.] NCI, NIH, Bethesda, MD 20892 USA.
[Cheng, Ka Wing; Wang, Mingfu] Univ Hong Kong, Sch Biol Sci, Hong Kong, Hong Kong, Peoples R China.
RP Dong, ZG (reprint author), Univ Minnesota, Hormel Inst, 801 16th Ave NE, Austin, MN 55009 USA.
EM zgdong@hi.umn.edu
RI Wang, Mingfu/D-3136-2009
FU Hormel Foundation; National Institutes of Health [R37 CA081064,
ES016548]; NCI [HHSN-261200533001C-NO1-CN-53301, N01-CN-43309-18018-01WA
13B]
FX This work was supported by The Hormel Foundation and National Institutes
of Health grants R37 CA081064 and ES016548 and NCI contract numbers
HHSN-261200533001C-NO1-CN-53301 and N01-CN-43309-18018-01WA 13B.
NR 35
TC 9
Z9 9
U1 2
U2 22
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 1
PY 2014
VL 74
IS 1
BP 243
EP 252
DI 10.1158/0008-5472.CAN-13-2245
PG 10
WC Oncology
SC Oncology
GA 284DZ
UT WOS:000329297600024
PM 24220240
ER
PT J
AU Hayman, TJ
Wahba, A
Rath, BH
Bae, H
Kramp, T
Shankavaram, UT
Camphausen, K
Tofilon, PJ
AF Hayman, Thomas J.
Wahba, Amy
Rath, Barbara H.
Bae, Heekyong
Kramp, Tamalee
Shankavaram, Uma T.
Camphausen, Kevin
Tofilon, Philip J.
TI The ATP-Competitive mTOR Inhibitor INK128 Enhances In Vitro and In Vivo
Radiosensitivity of Pancreatic Carcinoma Cells
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TRANSLATIONAL CONTROL; MESSENGER-RNAS; CANCER CELLS; INITIATION; EIF4E;
GAMMA-H2AX; THERAPY; TARGET
AB Purpose: Radiotherapy remains a primary treatment modality for pancreatic carcinoma, a tumor characterized by aberrant mTOR activity. Given the regulatory role of mTOR in gene translation, in this study, we defined the effects of the clinically relevant, ATP-competitive mTOR inhibitor, INK128 on the radiosensitivity of pancreatic carcinoma cell lines.
Experimental Design: Clonogenic survival was used to determine the effects of INK128 on in vitro radiosensitivity of three pancreatic carcinoma cell lines and a normal fibroblast cell line with mTOR activity defined using immunoblots. DNA double-strand breaks were evaluated according to gamma H2AX foci. The influence of INK128 on radiation-induced gene translation was determined by microarray analysis of polysome-bound mRNA. Leg tumor xenografts grown from pancreatic carcinoma cells were evaluated for mTOR activity, eIF4F cap complex formation, and tumor growth delay.
Results: INK128, while inhibiting mTOR activity in each of the cell lines, enhanced the in vitro radiosensitivity of the pancreatic carcinoma cells but had no effect on normal fibroblasts. The dispersal of radiation-induced gamma H2AX foci was inhibited in pancreatic carcinoma cells by INK128 as were radiation-induced changes in gene translation. Treatment of mice with INK128 resulted in an inhibition of mTOR activity as well as cap complex formation in tumor xenografts. Whereas INK128 alone had no effect of tumor growth rate, it enhanced the tumor growth delay induced by single and fractionated doses of radiation.
Conclusion: These results indicate that mTOR inhibition induced by INK128 enhances the radiosensitivity of pancreatic carcinoma cells and suggest that this effect involves the inhibition of DNA repair. (C)2013 AACR.
C1 [Hayman, Thomas J.] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
[Hayman, Thomas J.; Wahba, Amy; Rath, Barbara H.; Bae, Heekyong; Kramp, Tamalee; Shankavaram, Uma T.; Camphausen, Kevin; Tofilon, Philip J.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Tofilon, PJ (reprint author), NCI, 10 Ctr Dr MSC 1002,Bldg 10,B3B69B, Bethesda, MD 20892 USA.
EM tofilonp@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011373-03]
NR 29
TC 12
Z9 12
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2014
VL 20
IS 1
BP 110
EP 119
DI 10.1158/1078-0432.CCR-13-2136
PG 10
WC Oncology
SC Oncology
GA 284GC
UT WOS:000329303100014
PM 24198241
ER
PT J
AU Laurie, SA
Goss, GD
Shepherd, FA
Reaume, MN
Nicholas, G
Philip, L
Wang, L
Schwock, J
Hirsh, V
Oza, A
Tsao, MS
Wright, JJ
Leighl, NB
AF Laurie, Scott A.
Goss, Glenwood D.
Shepherd, Frances A.
Reaume, M. Neil
Nicholas, Garth
Philip, Lindsay
Wang, Lisa
Schwock, Joerg
Hirsh, Vera
Oza, Amit
Tsao, Ming-Sound
Wright, John J.
Leighl, Natasha B.
TI A Phase II Trial of Saracatinib, an Inhibitor of src Kinases, in
Previously-Treated Advanced Non-Small-Cell Lung Cancer: The Princess
Margaret Hospital Phase II Consortium
SO CLINICAL LUNG CANCER
LA English
DT Article
DE Biomarker; Non-small cell; Src inhibitor; Systemic therapy
ID FAMILY KINASES; SOLID TUMORS; AZD0530; CHEMOTHERAPY; DASATINIB;
DOCETAXEL; ERLOTINIB
AB Treatment options for advanced non-small-cell lung cancer (NSCLC) after failure of platinum-based chemotherapy are limited. Dysregulated src kinases may play a role in the malignant phenotype. This 2-stage phase II study evaluated saracatinib, an inhibitor of src kinases in this patient population, and responses were observed, including in a patient with an activating epidermal growth factor receptor (EGFR) mutation. Future studies of this class of agents in molecular subtypes of NSCLC are warranted.
Background: The src family of kinases may play a role in the malignant phenotype through effects on migration, motility, adhesion and proliferation. The activity of saracatinib, an orally available inhibitor of src kinases, was evaluated in patients with advanced, platinum-pretreated NSCLC. Patients and Methods: Eligible patients with advanced NSCLC of any histologic subtype and who had obtained a best response to prior platinum-based chemotherapy of at least stable disease received saracatanib 175 mg orally daily in a 28 day cycle. The primary end point was the proportion of patients progression-free after 4 cycles (16 weeks) of therapy; 8 such patients of 32 evaluable were required to deem the therapy active. Immunohistochemistry for src expression was performed on archival tissue from enrolled patients. Results: Thirty-seven patients received a median of 2 cycles (range, 1-14) each. Six of 31 evaluable patients were progression-free at 16 weeks. Two partial responses were observed, lasting 3.7 and 14.6 months; 1 responder had an EGFR exon 19 deletion. An additional 4 patients had stable disease for at least 4 cycles. The median progression-free and overall survival times were 1.8 and 7.6 months. No correlation between src protein expression and outcome was observed. Conclusions: There may be a subset of saracatinib-responsive NSCLC that is currently molecularly undefined. Further studies of this agent in a population preselected for target mutations that potentially relevant to src pathways, such as EGFR, should be considered. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Laurie, Scott A.; Goss, Glenwood D.; Reaume, M. Neil; Nicholas, Garth] Univ Ottawa, Ottawa Hosp, Ctr Canc, Ottawa, ON K1H 8L6, Canada.
[Shepherd, Frances A.; Philip, Lindsay; Wang, Lisa; Schwock, Joerg; Oza, Amit; Tsao, Ming-Sound; Leighl, Natasha B.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada.
[Hirsh, Vera] McGill Univ, Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada.
[Wright, John J.] NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Laurie, SA (reprint author), Univ Ottawa, Ottawa Hosp, Ctr Canc, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada.
EM slaurie@toh.on.ca
FU [HHSN261201100032C/NO1-CM-2011-00032]
FX Supported by contracts HHSN261201100032C/NO1-CM-2011-00032.
NR 22
TC 9
Z9 10
U1 3
U2 5
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1525-7304
EI 1938-0690
J9 CLIN LUNG CANCER
JI Clin. Lung Cancer
PD JAN
PY 2014
VL 15
IS 1
BP 52
EP 57
DI 10.1016/j.cllc.2013.08.001
PG 6
WC Oncology
SC Oncology
GA 281TZ
UT WOS:000329125200005
PM 24169259
ER
PT J
AU Goey, AKL
Meijerman, I
Rosing, H
Marchetti, S
Mergui-Roelvink, M
Keessen, M
Burgers, JA
Beijnen, JH
Schellens, JHM
AF Goey, Andrew K. L.
Meijerman, Irma
Rosing, Hilde
Marchetti, Serena
Mergui-Roelvink, Marja
Keessen, Marianne
Burgers, Jacobus A.
Beijnen, Jos H.
Schellens, Jan H. M.
TI The Effect of St John's Wort on the Pharmacokinetics of Docetaxel
SO CLINICAL PHARMACOKINETICS
LA English
DT Article
ID HUMAN HEPATOCYTE CULTURES; P-GLYCOPROTEIN INHIBITOR;
HYPERICUM-PERFORATUM; CONSTITUENT HYPERFORIN; IMATINIB MESYLATE;
DRUG-INTERACTIONS; CANCER-PATIENTS; INDUCTION; METABOLISM; IRINOTECAN
AB St John's wort (SJW), a herbal antidepressant, is commonly used by cancer patients, and its component hyperforin is a known inducer of the cytochrome P450 (CYP) isoenzyme 3A4. Here, the potential pharmacokinetic interaction between SJW and the sensitive CYP3A4 substrate docetaxel was investigated.
In ten evaluable cancer patients, the pharmacokinetics of docetaxel (135 mg administered intravenously over 60 min) were compared before and after 14 days of supplementation with SJW (300 mg extract [Hyperiplant(A (R))] three times daily).
SJW supplementation resulted in a statistically significant decrease in the mean area under the docetaxel plasma concentration-time curve extrapolated to infinity (AUC(a)) from 3,035 +/- A 756 to 2,682 +/- A 717 ng center dot A h/mL (P = 0.045). Furthermore, docetaxel clearance significantly increased from 47.2 to 53.7 L/h (P = 0.045) after SJW intake. The maximum plasma concentration and elimination half-life of docetaxel were (non-significantly) decreased after SJW supplementation. In addition, the incidence of docetaxel-related toxicities was lower after SJW supplementation.
These results suggest that concomitant use of docetaxel and the applied SJW product should be avoided to prevent potential undertreatment of cancer patients.
C1 [Goey, Andrew K. L.; Beijnen, Jos H.; Schellens, Jan H. M.] Univ Utrecht, Dept Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
[Meijerman, Irma] Univ Utrecht, Div Pharmacol, Dept Pharmaceut Sci, Utrecht, Netherlands.
[Rosing, Hilde; Beijnen, Jos H.] Netherlands Canc Inst, Dept Pharm & Pharmacol, Slotervaart Hosp, Amsterdam, Netherlands.
[Marchetti, Serena; Mergui-Roelvink, Marja; Keessen, Marianne; Schellens, Jan H. M.] Netherlands Canc Inst, Dept Clin Pharmacol, Amsterdam, Netherlands.
[Burgers, Jacobus A.] Netherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands.
RP Goey, AKL (reprint author), NCI, Clin Pharmacol Program, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM andrew.goey@nih.gov
FU Dutch Cancer Society [UU 2007-3795]
FX This work was supported by the Dutch Cancer Society [UU 2007-3795].
NR 43
TC 15
Z9 16
U1 1
U2 11
PU ADIS INT LTD
PI AUCKLAND
PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW
ZEALAND
SN 0312-5963
EI 1179-1926
J9 CLIN PHARMACOKINET
JI Clin. Pharmacokinet.
PD JAN
PY 2014
VL 53
IS 1
BP 103
EP 110
DI 10.1007/s40262-013-0102-5
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 283EZ
UT WOS:000329229900007
PM 24068654
ER
PT J
AU Sandler, NG
Sereti, I
AF Sandler, Netanya G.
Sereti, Irini
TI Can early therapy reduce inflammation?
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE biomarkers; HIV; inflammation; monocyte activation; morbidity; T-cell
activation
ID HIV-INFECTED PATIENTS; T-CELL-ACTIVATION; SUPPRESSIVE ANTIRETROVIRAL
THERAPY; IMMUNODEFICIENCY-VIRUS TYPE-1; BOOSTED PROTEASE INHIBITORS;
IMMUNE ACTIVATION; RALTEGRAVIR INTENSIFICATION; MICROBIAL TRANSLOCATION;
HIV-1-INFECTED PATIENTS; MYOCARDIAL-INFARCTION
AB Purpose of reviewSerious non-AIDS events or noninfectious complications of HIV infection far outnumber AIDS events in the current combination antiretroviral therapy (ART) era and are attributed to chronic inflammation. Thus, a better understanding of why inflammation persists on ART will assist in developing better therapeutic strategies, including optimal timing of ART initiation.Recent findingsMarkers of inflammation and coagulation, such as D-dimer, interleukin-6, C-reactive protein, soluble CD14, and soluble CD163, predict end-organ disease and mortality, whereas markers of T-cell activation appear more predictive of CD4 T-cell decline, AIDS events, or response to therapy. Initiating ART at high CD4 T-cell counts can result in less inflammation as supported by studies in acute and early HIV infection, but antiretroviral drugs may differentially affect inflammatory pathways. Decreasing inflammation in HIV-uninfected individuals may decrease morbidity, but long-term outcomes studies in HIV-infected individuals are lacking.SummaryCirculating biomarkers of inflammation are among the strongest predictors of non-AIDS outcomes in treated HIV infection. With additional investigation, they may serve in the future as specific end-organ disease surrogate endpoints and may help identify those patients at highest risk of non-AIDS events who may benefit from either early ART and/or potential adjuvant anti-inflammatory therapies.
C1 [Sandler, Netanya G.] Univ Texas Med Branch, Dept Internal Med, Infect Dis Div, Galveston, TX 77555 USA.
[Sereti, Irini] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Sandler, NG (reprint author), Univ Texas Med Branch, 301 Univ Blvd,Route 0435, Galveston, TX 77555 USA.
EM neutay@utmb.edu
OI Utay, Netanya/0000-0002-6407-8670
FU University of Texas Medical Branch at Galveston; Intramural Research
Program of NIAID
FX The work of N.S. was supported by the University of Texas Medical Branch
at Galveston. The work of I. S. was supported by the Intramural Research
Program of NIAID. The authors have no conflicts of interest to declare.
NR 99
TC 12
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
EI 1746-6318
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD JAN
PY 2014
VL 9
IS 1
BP 72
EP 79
DI 10.1097/COH.0000000000000020
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 282PW
UT WOS:000329185500011
PM 24247669
ER
PT J
AU Prasad, B
Evers, R
Gupta, A
Hop, CECA
Salphati, L
Shukla, S
Ambudkar, SV
Unadkat, JD
AF Prasad, Bhagwat
Evers, Raymond
Gupta, Anshul
Hop, Cornelis E. C. A.
Salphati, Laurent
Shukla, Suneet
Ambudkar, Suresh V.
Unadkat, Jashvant D.
TI Interindividual Variability in Hepatic Organic Anion-Transporting
Polypeptides and P-Glycoprotein (ABCB1) Protein Expression:
Quantification by Liquid Chromatography Tandem Mass Spectroscopy and
Influence of Genotype, Age, and Sex
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID RESISTANCE-ASSOCIATED PROTEIN-2; DRUG-DRUG INTERACTIONS; OATP-C; HUMAN
LIVER; UDP-GLUCURONOSYLTRANSFERASES; SLCO1B1 POLYMORPHISMS;
PLASMA-CONCENTRATIONS; HUMAN HEPATOCYTES; GEMFIBROZIL; CERIVASTATIN
AB Interindividual variability in protein expression of organic anion-transporting polypeptides (OATPs) OATP1B1, OATP1B3, OATP2B1, and multidrug resistance-linked P-glycoprotein (P-gp) or ABCB1 was quantified in frozen human livers (n = 64) and cryopreserved human hepatocytes (n = 12) by a validated liquid chromatography tandem mass spectroscopy (LC-MS/MS) method. Membrane isolation, sample workup, and LC-MS/MS analyses were as described before by our laboratory. Briefly, total native membrane proteins, isolated from the liver tissue and cryopreserved hepatocytes, were trypsin digested and quantified by LC-MS/MS using signature peptide(s) unique to each transporter. The mean 6 S. D. (maximum/minimum range in parentheses) protein expression (fmol/mu g of membrane protein) in human liver tissue was OATP1B1-2.0 +/- 0.9 (7), OATP1B3-1.1 +/- 0.5 (8), OATP2B1-1 1.7 +/- 0.6 (5), and P-gp- 0.4 +/- 0.2 (8). Transporter expression in the liver tissue was comparable to that in the cryopreserved hepatocytes. Most important is that livers with SLCO1B1 (encoding OATP1B1) haplotypes *14/*14 and *14/*1a [i.e., representing single nucleotide polymorphisms (SNPs), c.388A > G, and c.463C > A] had significantly higher (P < 0.0001) protein expression than the reference haplotype (*1a/*1a). Based on these genotype-dependent protein expression data, we predicted (using Simcyp) an up to similar to 40% decrease in the mean area under the curve of rosuvastatin or repaglinide in subjects harboring these variant alleles compared with those harboring the reference alleles. SLCO1B3 (encoding OATP1B3) SNPs did not significantly affect protein expression. Age and sex were not associated with transporter protein expression. These data will facilitate the prediction of population-based human transporter-mediated drug disposition, drug-drug interactions, and interindividual variability through physiologically based pharmacokinetic modeling.
C1 [Prasad, Bhagwat; Unadkat, Jashvant D.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Evers, Raymond] Merck & Co Inc, Pharmacokinet Pharmacodynam & Drug Metab, Rahway, NJ 07065 USA.
[Gupta, Anshul] AstraZeneca Pharmaceut LLP, Infect DMPK, Drug Metab & Pharmacokinet, Waltham, MA USA.
[Hop, Cornelis E. C. A.; Salphati, Laurent] Genentech Inc, Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA.
[Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Unadkat, JD (reprint author), Univ Washington, Dept Pharmaceut, POB 357610, Seattle, WA 98195 USA.
EM jash@u.washington.edu
FU University of Washington Research Affiliate Program on Transporters;
AstraZeneca; Genentech; Merck Co., Inc.; Merck Research Laboratories New
Technologies Review and Licensing Committee; Intramural Research Program
of the National Institutes of Health National Cancer Institute Center
for Cancer Research [ZIA BC010030-13]
FX This study was supported by the University of Washington Research
Affiliate Program on Transporters sponsored by AstraZeneca, Genentech,
and Merck & Co., Inc. (http://sop.washington.edu/uwrapt). R.E. thanks
the Merck Research Laboratories New Technologies Review and Licensing
Committee for funding. A. G. thanks the AstraZeneca External Science
Committee and licensing group for their support. S. S. and S. V. A were
supported by the Intramural Research Program of the National Institutes
of Health National Cancer Institute Center for Cancer Research (grant
number ZIA BC010030-13).
NR 44
TC 54
Z9 54
U1 0
U2 12
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
EI 1521-009X
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD JAN
PY 2014
VL 42
IS 1
BP 78
EP 88
DI 10.1124/dmd.113.053819
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 286XI
UT WOS:000329502200010
PM 24122874
ER
PT J
AU Concheiro, M
Baumann, MH
Scheidweiler, KB
Rothman, RB
Marrone, GF
Huestis, MA
AF Concheiro, Marta
Baumann, Michael H.
Scheidweiler, Karl B.
Rothman, Richard B.
Marrone, Gina F.
Huestis, Marilyn A.
TI Nonlinear Pharmacokinetics of (+/-)3, 4-Methylenedioxymethamphetamine
(MDMA) and Its Pharmacodynamic Consequences in the Rat
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; MAIN METABOLITES; ECSTASY;
HUMANS; NEUROTOXICITY; PLASMA; AMPHETAMINE; DISPOSITION;
METHYLENEDIOXYMETHAMPHETAMINE; (+/-)-3,4-METHYLENEDIOXYMETHAMPHETAMINE
AB 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA's safety are needed. We evaluated MDMA's pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (+/-)-3,4-dihydroxymethamphetamine (HHMA), (+/-)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (6)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography-tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA C-max was 164 +/- 47.1 ng/ml, HHMA and HMMA were major metabolites, and <20% of MDMA was metabolized to MDA. After 5- and 10-mg/ kg doses, MDMA areas under the curve (AUCs) were 3- and 10-fold greater than those after 2.5 mg/kg; HHMA and HMMA AUC values were relatively constant across doses; and MDA AUC values were greater than dose-proportional. Our data provide decisive in vivo evidence that MDMA and MDA display nonlinear accumulation via metabolic autoinhibition in the rat. Importantly, 5-HT syndrome severity correlated with MDMA concentrations (r = 0.8083; P < 0.0001) and core temperature correlated with MDA concentrations (r = 0.7595; P < 0.0001), suggesting that MDMA's behavioral and hyperthermic effects may involve distinct mechanisms. Given key similarities between MDMA pharmacokinetics in rats and humans, data from rats can be useful when provided at clinically relevant doses.
C1 [Concheiro, Marta; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA.
[Baumann, Michael H.; Rothman, Richard B.] NIDA, Designer Drug Res Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Marrone, Gina F.] Weill Cornell Med Coll, Dept Neurosci, New York, NY USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institutes of Health
National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Institute on Drug Abuse.
NR 45
TC 10
Z9 10
U1 1
U2 16
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
EI 1521-009X
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD JAN
PY 2014
VL 42
IS 1
BP 119
EP 125
DI 10.1124/dmd.113.053678
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 286XI
UT WOS:000329502200015
PM 24141857
ER
PT J
AU Torre, P
Hoffman, HJ
Springer, G
Cox, C
Young, M
Margolick, JB
Plankey, M
AF Torre, Peter, III
Hoffman, Howard J.
Springer, Gayle
Cox, Christopher
Young, Mary
Margolick, Joseph B.
Plankey, Michael
TI Cochlear Function Among HIV-Seropositive and HIV-Seronegative Men and
Women
SO EAR AND HEARING
LA English
DT Article
DE Cochlear function; Multicenter AIDS Cohort Study; Women's Interagency
HIV Study
ID MULTICENTER AIDS COHORT; ACQUIRED-IMMUNODEFICIENCY-SYNDROME;
DIABETES-MELLITUS; INTERAGENCY HIV; EMISSIONS; HEARING; ADULTS
AB Objectives: There is limited research about cochlear function in adults who are human immunodeficiency virus (HIV) positive (+). The aim of the present study was to collect measures of cochlear function in a large sample of adults with, or at risk for, HIV infection, to evaluate associations between HIV status, HIV treatment, and cochlear function.
Design: Distortion product otoacoustic emissions (DPOAEs) were used to evaluate cochlear function in 506 participants; 329 men, 150 of whom were HIV+, and 177 women, 136 of whom were HIV+. DPOAEs were measured at frequencies 1000, 2000, 3000, 4000, and 6000 Hz. A DPOAE nonresponse (NR) was defined as an absolute DPOAE level less than -15 dB SPL or a difference between the absolute DPOAE level and the background noise level less than 6 dB. The total number of NRs was calculated for each ear. The associations of demographic variables, HIV status, and HIV treatment with number of NRs were evaluated with univariate and multivariate ordinal regression models.
Results: There was a statistically significant increase in the odds of higher numbers of NRs with age, being male, and being non-Black, but not with HIV status. Among HIV+ participants, there were no statistically significant associations of the HIV disease status or treatment variables with higher number of NRs.
Conclusion: The authors found no evidence of impaired cochlear function by HIV disease status or highly active antiretroviral therapy-treated HIV infection in this cross-sectional study.
C1 [Torre, Peter, III] San Diego State Univ, Sch Speech Language & Hearing Sci, San Diego, CA 92182 USA.
[Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders NIDCD, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
[Springer, Gayle; Cox, Christopher] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Young, Mary; Plankey, Michael] Georgetown Univ, Med Ctr, Dept Med, Div Infect Dis, Wa, DC USA.
[Margolick, Joseph B.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
RP Torre, P (reprint author), San Diego State Univ, Sch Speech Language & Hearing Sci, 5500 Campanile Dr,SLHS 244, San Diego, CA 92182 USA.
EM ptorre@mail.sdsu.edu
FU National Institute on Deafness and Other Communication Disorders,
National Institutes of Health via interagency agreement; National
Institute of Allergy and Infectious Diseases for Cooperative Agreements
[U01 AI-035042-18, U01 AI-034994-17]
FX Supported by the National Institute on Deafness and Other Communication
Disorders, National Institutes of Health via interagency agreement with
National Institute of Allergy and Infectious Diseases for Cooperative
Agreements U01 AI-035042-18 (Multicenter AIDS Cohort Study) and U01
AI-034994-17 (Women's Interagency HIV Study). Support of the
Baltimore-Washington, DC Multicenter AIDS Cohort Study site was provided
by the National Institute of Allergy and Infectious Diseases, with
additional supplemental funding from the National Cancer Institute
(U01-AI-35042, UL1-RR025005 [General Clinic Research Center]). Support
of the Metropolitan Washington, DC Women's Interagency HIV Study site,
was provided by the National Institute of Allergy and Infectious
Diseases (U01-AI-34994) and by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (U01-HD-32632).
NR 26
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Z9 4
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-0202
EI 1538-4667
J9 EAR HEARING
JI Ear Hear.
PD JAN-FEB
PY 2014
VL 35
IS 1
BP 56
EP 62
DI 10.1097/AUD.0b013e3182a021c8
PG 7
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 285CE
UT WOS:000329370000009
PM 24080949
ER
PT J
AU King, KA
Gordon-Salant, S
Yanjanin, N
Zalewski, C
Houser, A
Porter, FD
Brewer, CC
AF King, Kelly A.
Gordon-Salant, Sandra
Yanjanin, Nicole
Zalewski, Christopher
Houser, Ari
Porter, Forbes D.
Brewer, Carmen C.
TI Auditory Phenotype of Niemann-Pick Disease, Type C1
SO EAR AND HEARING
LA English
DT Article
DE Niemann-Pick Type C; NPC; Hearing; Auditory phenotype
ID CHOLESTEROL; RESPONSES; FIBROBLASTS; HEARING; GENE
AB Objectives: The aim of this study was to comprehensively evaluate the auditory phenotype in Niemann-Pick disease, type C1 (NPC1), to understand better the natural history of this complex, heterogeneous disorder, and to define further the baseline auditory deficits associated with NPC1 so that use of potentially ototoxic interventions (e.g., 2-hydroxypropyl-ss-cyclodextrin) may be more appropriately monitored and understood.
Design: Fifty patients with NPC1 ranging in age from 4 months to 21 years (mean = 9.3 years) enrolled in a natural history/observational study at the National Institutes of Health. The auditory test battery included, when possible, immittance audiometry, pure-tone and speech audiometry, otoacoustic emission testing, and a neurotologic auditory brainstem response study. Longitudinal data were collected on a subset of patients.
Results: Over half of the cohort exhibited hearing loss involving the high frequencies ranging from a slight to moderate degree, and 74% of patients presented with clinically significant hearing loss involving the frequencies most important to speech understanding (0.5, 1, 2, 4kHz). Despite the heterogeneity of the sample, results among patients were sufficiently consistent to implicate retrocochlear dysfunction in the majority (66%) of individuals, with (22%) or without (44%) accompanying cochlear involvement. Some patients (10%) presented with a profile for auditory neuropathy spectrum disorder. The combination of cross-sectional and longitudinal data indicates these patients are at risk for a progressive decline in auditory function.
Conclusions: This is the largest cohort of patients with NPC1 evaluated comprehensively for auditory dysfunction, and results implicate the pathological processes of NPC1 in the manifestation of hearing loss. Patients with NPC1 should be monitored audiologically throughout their lives, beginning at the time of diagnosis. Clinicians and researchers should be aware of this historically overlooked aspect of the phenotype.
C1 [King, Kelly A.; Zalewski, Christopher; Brewer, Carmen C.] Natl Inst Deafness & Other Commun Disorders, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Gordon-Salant, Sandra] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA.
[Yanjanin, Nicole; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept HHS, NIH, Bethesda, MD USA.
[Houser, Ari] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
RP Brewer, CC (reprint author), Natl Inst Deafness & Other Commun Disorders, US Dept HHS, NIH, 10 Ctr Dr,Bldg 10-5C306, Bethesda, MD 20892 USA.
EM brewerc@nidcd.nih.gov
FU National Institutes of Health (NIH) training grant [T32DC000046];
National Institute on Deafness and Other Communication Disorders; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; NIH Office of Rare diseases; NIH Clinical Research Center;
Ara Parseghian Medical Research Foundation; Dana's Angels Research Trust
FX This work was supported, in part, by a National Institutes of Health
(NIH) training grant (T32DC000046) to Kelly A. King, and by the
intramural divisions of the National Institute on Deafness and Other
Communication Disorders and the Eunice Kennedy Shriver National
Institute of Child Health and Human Development. Further support came
from a Bench-to-Bedside award from the NIH Office of Rare diseases and
the NIH Clinical Research Center, and from both the Ara Parseghian
Medical Research Foundation and Dana's Angels Research Trust.
NR 28
TC 10
Z9 10
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-0202
EI 1538-4667
J9 EAR HEARING
JI Ear Hear.
PD JAN-FEB
PY 2014
VL 35
IS 1
BP 110
EP 117
DI 10.1097/AUD.0b013e3182a362b8
PG 8
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 285CE
UT WOS:000329370000014
PM 24225652
ER
PT J
AU Liu, WX
Shang, YL
Zeng, Y
Liu, C
Li, YC
Zhai, LH
Wang, P
Lou, JZ
Xu, P
Ye, YH
Li, W
AF Liu, Weixiao
Shang, Yongliang
Zeng, Yan
Liu, Chao
Li, Yanchang
Zhai, Linhui
Wang, Pan
Lou, Jizhong
Xu, Ping
Ye, Yihong
Li, Wei
TI Dimeric Ube2g2 simultaneously engages donor and acceptor ubiquitins to
form Lys48-linked ubiquitin chains
SO EMBO JOURNAL
LA English
DT Article
DE E2 dimerization; ER-associated degradation/ERAD; K48-linked ubiquitin
chain; linkage specificity; ubiquitination mechanism
ID HMG-COA REDUCTASE; CONJUGATING ENZYME; ENDOPLASMIC-RETICULUM;
POLYUBIQUITIN CHAINS; CRYSTAL-STRUCTURE; E1 ENZYMES; E2; LIGASE;
COMPLEX; GP78
AB Cellular adaptation to proteotoxic stress at the endoplasmic reticulum (ER) depends on Lys48-linked polyubiquitination by ER-associated ubiquitin ligases (E3s) and subsequent elimination of ubiquitinated retrotranslocation products by the proteasome. The ER-associated E3 gp78 ubiquitinates misfolded proteins by transferring preformed Lys48-linked ubiquitin chains from the cognate E2 Ube2g2 to substrates. Here we demonstrate that Ube2g2 synthesizes linkage specific ubiquitin chains by forming an unprecedented homodimer: The dimerization of Ube2g2, mediated primarily by electrostatic interactions between two Ube2g2s, is also facilitated by the charged ubiquitin molecules. Mutagenesis studies show that Ube2g2 dimerization is required for ER-associated degradation (ERAD). In addition to E2 dimerization, we show that a highly conserved arginine residue in the donor Ube2g2 senses the presence of an aspartate in the acceptor ubiquitin to position only Lys48 of ubiquitin in proximity to the donor E2 active site. These results reveal an unanticipated mode of E2 self-association that allows the E2 to effectively engage two ubiquitins to specifically synthesize Lys48-linked ubiquitin chains.
C1 [Liu, Weixiao; Shang, Yongliang; Liu, Chao; Wang, Pan; Li, Wei] Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing, Peoples R China.
[Zeng, Yan; Lou, Jizhong] Chinese Acad Sci, Inst Biophys, Lab Noncoding RNAs, Beijing 100080, Peoples R China.
[Li, Yanchang; Zhai, Linhui; Xu, Ping] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China.
[Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, W (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing, Peoples R China.
EM yihongy@mail.nih.gov; leways@ioz.ac.cn
FU National Natural Science Foundation of China [30970603]; Major Basic
Research Program [2012CB944404]; Knowledge Innovation Program
[KSCX2-YW-N-071]; One Hundred Talents Program of Chinese Academy of
Sciences; intramural research program at NIDDK of the National
Institutes of Health, USA
FX We thank Xinhua Lin and Jun Tang for critical reading of the manuscript,
Huimin Wang and Jianwu Wang for their assistance in the Biolayer
Interferometry study. This work is supported by a National Natural
Science Foundation of China (Grant No. 30970603), the Major Basic
Research Program (Grant No. 2012CB944404), the Knowledge Innovation
Program (Grant No. KSCX2-YW-N-071), the One Hundred Talents Program of
Chinese Academy of Sciences, and the intramural research program at
NIDDK of the National Institutes of Health, USA.
NR 50
TC 18
Z9 18
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0261-4189
EI 1460-2075
J9 EMBO J
JI Embo J.
PD JAN
PY 2014
VL 33
IS 1
BP 46
EP 61
DI 10.1002/embj.201385315
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 284UL
UT WOS:000329346500007
PM 24366945
ER
PT J
AU Starling, AP
Engel, SM
Whitworth, KW
Richardson, DB
Stuebe, AM
Daniels, JL
Haug, LS
Eggesbo, M
Becher, G
Sabaredzovic, A
Thomsen, C
Wilson, RE
Travlos, GS
Hoppin, JA
Baird, DD
Longnecker, MP
AF Starling, Anne P.
Engel, Stephanie M.
Whitworth, Kristina W.
Richardson, David B.
Stuebe, Alison M.
Daniels, Julie L.
Haug, Line Smastuen
Eggesbo, Merete
Becher, Georg
Sabaredzovic, Azemira
Thomsen, Cathrine
Wilson, Ralph E.
Travlos, Gregory S.
Hoppin, Jane A.
Baird, Donna D.
Longnecker, Matthew P.
TI Perfluoroalkyl substances and lipid concentrations in plasma during
pregnancy among women in the Norwegian Mother and Child Cohort Study
SO ENVIRONMENT INTERNATIONAL
LA English
DT Article
DE The Norwegian Mother and Child Cohort Study MoBa; Perfluoroalkyl
substances; Perfluorooctanoic acid; Perfluorooctane sulfonate
ID ACTIVATED RECEPTOR-ALPHA; PERFLUOROOCTANOIC ACID; PERFLUORINATED
COMPOUNDS; SERUM-LIPIDS; DENSITY-LIPOPROTEIN; HDL CHOLESTEROL;
PREECLAMPSIA; EXPOSURE; RISK; APOLIPOPROTEINS
AB Background: Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia.
Methods: This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted.
Results: Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2 mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol; and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI = 2.5, 4.9).
Conclusion: Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal. Published by Elsevier Ltd.
C1 [Starling, Anne P.; Hoppin, Jane A.; Baird, Donna D.; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Starling, Anne P.; Engel, Stephanie M.; Richardson, David B.; Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Whitworth, Kristina W.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, San Antonio, TX USA.
[Stuebe, Alison M.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
[Stuebe, Alison M.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA.
[Haug, Line Smastuen; Eggesbo, Merete; Becher, Georg; Sabaredzovic, Azemira; Thomsen, Cathrine] Norwegian Inst Publ Hlth, Oslo, Norway.
[Wilson, Ralph E.; Travlos, Gregory S.] NIEHS, Cellular & Mol Pathol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM longnec1@niehs.nih.gov
RI Baird, Donna/D-5214-2017;
OI Baird, Donna/0000-0002-5544-2653; Longnecker,
Matthew/0000-0001-6073-5322; Eggesbo, Merete/0000-0002-0006-5336
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences; National Institute of Environmental
Health Sciences [1-F30-ES022126-01]; Norwegian Ministry of Health;
Ministry of Education and Research; NIH/NIEHS [N01-ES-75558]; NIH/NINDS
[1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Norwegian Research
Council/FUGE [151918/S10]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences. A.P.
Starling was supported by an extramural award (1-F30-ES022126-01) from
the National Institute of Environmental Health Sciences. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health. The
Norwegian Mother and Child Cohort Study is supported by the Norwegian
Ministry of Health and the Ministry of Education and Research, NIH/NIEHS
(contract no. N01-ES-75558), NIH/NINDS (grant no.1 UO1 NS 047537-01,
grant no.2 UO1 NS 047537-06A1), and the Norwegian Research Council/FUGE
(grant no. 151918/S10). We are grateful to all the participating
families in Norway who take part in this ongoing cohort study.
NR 64
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U1 4
U2 36
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD JAN
PY 2014
VL 62
BP 104
EP 112
DI 10.1016/j.envint.2013.10.004
PG 9
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA 280BF
UT WOS:000329003000012
PM 24189199
ER
PT J
AU Schisterman, EF
Mumford, SL
Sjaarda, LA
AF Schisterman, Enrique F.
Mumford, Sunni L.
Sjaarda, Lindsey A.
TI Failure to Consider the Menstrual Cycle Phase May Cause
Misinterpretation of Clinical and Research Findings of Cardiometabolic
Biomarkers in Premenopausal Women
SO EPIDEMIOLOGIC REVIEWS
LA English
DT Article
DE biomarkers, cardiometabolic; inflammation; menstrual cycle; variability
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; ENDOGENOUS REPRODUCTIVE
HORMONES; HEALTHY-YOUNG WOMEN; ESTROGEN PLUS PROGESTIN;
LOW-DENSITY-LIPOPROTEIN; SERUM URIC-ACID; CARDIOVASCULAR-DISEASE;
SEX-HORMONES; INSULIN SENSITIVITY
AB Biomarker assessment plays a critical role in the study and prevention of disease. However, variation in biomarkers attributable to the menstrual cycle in premenopausal women may impair understanding the role of certain biomarkers in disease development and progression. Thus, in light of the recently increasing evidence of menstrual cycle variability in multiple cardiometabolic biomarkers, a reexamination of approaches for appropriately studying and diagnosing cardiovascular disease in premenopausal women is warranted. We reviewed studies (from 1934 through 2012) evaluating changes in cardiometabolic biomarkers across phases of the menstrual cycle, including markers of oxidative stress, lipids, insulin sensitivity, and systemic inflammation. Each was observed to vary significantly during the menstrual cycle. For example, nearly twice as many women had elevated cholesterol levels warranting therapy (>= 200 mg/dL) during the follicular phase compared with the luteal phase (14.3% vs. 7.9%), with only 3% having consistently high levels during all phases of the cycle. Similarly, nearly twice as many women were classified as being at an elevated risk of cardiovascular disease (high sensitivity C-reactive protein >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%). Menstrual cycle-associated variability in cardiometabolic biomarkers is an important source of variability that should be accounted for in both research and clinical settings.
C1 [Schisterman, Enrique F.; Mumford, Sunni L.; Sjaarda, Lindsey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Suite 7B03N, Bethesda, MD 20892 USA.
EM schistee@mail.nih.gov
OI Sjaarda, Lindsey/0000-0003-0539-8110; Schisterman,
Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development at the National Institutes of Health [HHSN275200403394C]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
at the National Institutes of Health (contract HHSN275200403394C).
NR 89
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Z9 16
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0193-936X
EI 1478-6729
J9 EPIDEMIOL REV
JI Epidemiol. Rev.
PY 2014
VL 36
IS 1
SI SI
BP 71
EP 82
DI 10.1093/epirev/mxt007
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 281WK
UT WOS:000329131500007
PM 24042431
ER
PT J
AU Lynge, E
Ponti, A
James, T
Majek, O
von Euler-Chelpin, M
Anttila, A
Fitzpatrick, P
Frigerio, A
Kawai, M
Scharpantgen, A
Broeders, M
Hofvind, S
Vidal, C
Ederra, M
Salas, D
Bulliard, JL
Tomatis, M
Kerlikowske, K
Taplin, S
AF Lynge, Elsebeth
Ponti, Antonio
James, Ted
Majek, Ondrej
von Euler-Chelpin, My
Anttila, Ahti
Fitzpatrick, Patricia
Frigerio, Alfonso
Kawai, Masaaki
Scharpantgen, Astrid
Broeders, Mireille
Hofvind, Solveig
Vidal, Carmen
Ederra, Maria
Salas, Dolores
Bulliard, Jean-Luc
Tomatis, Mariano
Kerlikowske, Karla
Taplin, Stephen
CA ICSN DCIS Working Grp
TI Variation in detection of ductal carcinoma in situ during screening
mammography: A survey within the International Cancer Screening Network
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Breast cancer; Ductal carcinoma in situ (DCIS); Screening mammography;
Cancer registration
ID BREAST-CANCER; PROGRAM; WOMEN; MORTALITY; DIAGNOSIS; OUTCOMES; SCIENCE;
TRENDS; IMPACT; STATE
AB Background: There is concern about detection of ductal carcinoma in situ (DCIS) in screening mammography. DCIS accounts for a substantial proportion of screen-detected lesions but its effect on breast cancer mortality is debated. The International Cancer Screening Network conducted a comparative analysis to determine variation in DCIS detection.
Patients and Methods: Data were collected during 2004-2008 on number of screening examinations, detected breast cancers, DCIS cases and Globocan 2008 breast cancer incidence rates derived from national or regional cancer registers. We calculated screen-detection rates for breast cancers and DCIS.
Results: Data were obtained from 15 screening settings in 12 countries; 7,176,050 screening examinations; 29,605 breast cancers and 5324 DCIS cases. The ratio between highest and lowest breast cancer incidence was 2.88 (95% confidence interval (CI) 2.76-3.00); 2.97 (95% CI 2.51-3.51) for detection of breast cancer; and 3.49 (95% CI 2.70-4.51) for detection of DCIS.
Conclusions: Considerable international variation was found in DCIS detection. This variation could not be fully explained by variation in incidence nor in breast cancer detection rates. It suggests the potential for wide discrepancies in management of DCIS resulting in overtreatment of indolent DCIS or undertreatment of potentially curable disease. Comprehensive cancer registration is needed to monitor DCIS detection. Efforts to understand discrepancies and standardise management may improve care. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Lynge, Elsebeth; von Euler-Chelpin, My] Univ Copenhagen, Dept Publ Hlth, DK-1014 Copenhagen K, Denmark.
[Ponti, Antonio; Tomatis, Mariano] AOU San Giovanni Battista, CPO Piemonte, Turin, Italy.
[James, Ted] Univ Vermont, Dept Surg, Burlington, VT 05405 USA.
[Majek, Ondrej] Masaryk Univ, Inst Biostat & Anal, Brno, Czech Republic.
[Anttila, Ahti] Finnish Canc Registry, Mass Screening Registry, FIN-00170 Helsinki, Finland.
[Fitzpatrick, Patricia] Natl Canc Screening Serv, Dublin, Ireland.
[Frigerio, Alfonso] Reg Reference Ctr Breast Canc Screening, Turin, Italy.
[Kawai, Masaaki] Tohoku Univ, Grad Sch Med, Dept Surg Oncol, Sendai, Miyagi 980, Japan.
[Scharpantgen, Astrid] Direct Sante, Programme Mammog, Luxembourg, Luxembourg.
[Broeders, Mireille] Natl Expert & Training Ctr Breast Canc Screening, Nijmegen, Netherlands.
[Hofvind, Solveig] Canc Registry Norway, Oslo, Norway.
[Vidal, Carmen] Catalan Inst Oncol, Canc & Prevent Control Program, Barcelona, Spain.
[Ederra, Maria] Inst Salud Publ, Breast Canc Screening Program, Navarra, Spain.
[Salas, Dolores] Gen Directorate Res & Publ Hlth, Valencia, Spain.
[Salas, Dolores] Ctr Publ Hlth Res, Valencia, Spain.
[Bulliard, Jean-Luc] Univ Lausanne Hosp, Epalinges, Switzerland.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Med & Epidemiol & Biostatist, San Francisco, CA 94143 USA.
[Taplin, Stephen] Natl Canc Inst, Div Canc Control & Populat Sci, Behav Res Program, Bethesda, MD USA.
RP Lynge, E (reprint author), Univ Copenhagen, Dept Publ Hlth, Ostre Farimagsgade 5, DK-1014 Copenhagen K, Denmark.
EM elsebeth@sund.ku.dk
RI Garcia, Montse/B-8832-2014; Broeders, Mireille/C-8820-2015;
OI Garcia, Montse/0000-0002-3437-3185; Fitzpatrick,
Patricia/0000-0003-2524-3677; Lynge, Elsebeth/0000-0003-4785-5236;
Vidal, Carmen/0000-0003-2768-2710
FU National Cancer Institute [U01CA63740, U01CA86076, U01CA86082,
U01CA63736, U01CA 70013, U01CA69976, U01CA63731, U01CA70040]
FX The collection of US data was supported by the National Cancer
Institute-funded Breast Cancer Surveillance Consortium co-operative
agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA 70013,
U01CA69976, U01CA63731, U01CA70040). A list of the BCSC investigators
and procedures for requesting BCSC data for research purposes are
provided at: http://breastscreening.cancer.gov/. The collection of
cancer data used in this study was supported in part by several state
public health departments and cancer registries throughout the U.S. For
a full description of these sources, please see:
http://breastscreening.cancer.gov/work/acknowledgement.html. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or the
National Institutes of Health. We thank Weiwei Zhu at the Statistical
Coordinating Center for preparing the BCSC data for the manuscript.
Coordination for this study was provided by the U.S. National Cancer
Institute, Bethesda, Maryland. Data management and analysis were
provided by CPO Piemonte, Torino, Italy. We thank the participating
women, mammography facilities and radiologists for the data they have
provided for this study.
NR 21
TC 12
Z9 12
U1 1
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD JAN
PY 2014
VL 50
IS 1
BP 185
EP 192
DI 10.1016/j.ejca.2013.08.013
PG 8
WC Oncology
SC Oncology
GA 282KO
UT WOS:000329170300020
PM 24041876
ER
PT J
AU Moore, KR
Smith, JS
Laughlin-Tommaso, SK
Baird, DD
AF Moore, Kristen R.
Smith, Jennifer S.
Laughlin-Tommaso, Shannon K.
Baird, Donna D.
TI Cervical neoplasia-related factors and decreased prevalence of uterine
fibroids among a cohort of African American women
SO FERTILITY AND STERILITY
LA English
DT Article
DE Uterine fibroids; cervical neoplasia; cervical treatment; abnormal Pap
smear; colposcopy
ID HUMAN-PAPILLOMAVIRUS; DNA METHYLATION; REPRODUCTIVE FACTORS;
CANCER-SOCIETY; RISK; LEIOMYOMATA; ABNORMALITIES; INFECTION; FREQUENCY;
GENETICS
AB Objective: To investigate whether the previously reported inverse association between cervical neoplasia and uterine fibroids is corroborated.
Design: Cross-sectional analysis of enrollment data from an ongoing prospective study of fibroid development.
Setting: Not applicable.
Patient(s): Self-reported data on abnormal Pap smear, colposcopy, and cervical treatment were obtained from 1,008 African American women ages 23-34 with no previous fibroid diagnosis and no reported history of human papillomavirus vaccination. Presence of fibroids was assessed at a standardized ultrasound examination.
Intervention(s): None.
Main Outcome Measure(s): The association between the three cervical neoplasia-related variables and the presence of fibroids was evaluated with logistic regression to estimate age-adjusted and multivariable-adjusted odds ratios (aORs).
Result(s): Of the analysis sample, 46%, 29%, and 14% reported a prior abnormal Pap smear, colposcopy, and cervical treatment, respectively. Twenty-five percent had fibroids at ultrasound. Those reporting cervical treatment had a 39% (aOR, 0.61; 95% confidence interval [CI] [0.38-0.96]) reduction in fibroid risk. Weak nonsignificant associations were found for abnormal Pap smear and colposcopy.
Conclusion(s): Although a protective-type association of cervical neoplasia with uterine fibroids seems counterintuitive, a causal pathway is possible, and the findings are consistent with two prior studies. Further investigation is needed on the relationship between fibroids and cervical neoplasia and human papillomavirus-related mechanisms. (Fertil Steril (R) 2014; 101: 208-14. (C) 2014 by American Society for Reproductive Medicine.)
C1 [Moore, Kristen R.; Smith, Jennifer S.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Moore, Kristen R.; Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Laughlin-Tommaso, Shannon K.] Mayo Clin, Dept Obstet & Gynecol, Ctr Uterine Fibroids, Rochester, MN USA.
RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, A3-05, Res Triangle Pk, NC 27709 USA.
EM baird@niehs.nih.gov
RI Moore, Kristen/C-2303-2017; Baird, Donna/D-5214-2017
OI Moore, Kristen/0000-0001-9993-3270; Baird, Donna/0000-0002-5544-2653
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences [10-E-N044]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences (10-E-N044).
NR 34
TC 7
Z9 7
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JAN
PY 2014
VL 101
IS 1
BP 208
EP 214
DI 10.1016/j.fertnstert.2013.09.021
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 281VJ
UT WOS:000329128800040
PM 24268705
ER
PT J
AU Legro, RS
Brzyski, RG
Diamond, MP
Coutifaris, C
Schlaff, WD
Alvero, R
Casson, P
Christman, GM
Huang, H
Yan, QY
Haisenleder, DJ
Barnhart, KT
Bates, GW
Usadi, R
Lucidi, R
Baker, V
Trussell, JC
Krawetz, SA
Snyder, P
Ohl, D
Santoro, N
Eisenberg, E
Zhang, HP
AF Legro, Richard S.
Brzyski, Robert G.
Diamond, Michael P.
Coutifaris, Christos
Schlaff, William D.
Alvero, Ruben
Casson, Peter
Christman, Gregory M.
Huang, Hao
Yan, Qingshang
Haisenleder, Daniel J.
Barnhart, Kurt T.
Bates, G. Wright
Usadi, Rebecca
Lucidi, Richard
Baker, Valerie
Trussell, J. C.
Krawetz, Stephen A.
Snyder, Peter
Ohl, Dana
Santoro, Nanette
Eisenberg, Esther
Zhang, Heping
CA Natl Inst Child Hlth Human Dev Rep
TI The Pregnancy in Polycystic Ovary Syndrome II study: baseline
characteristics and effects of obesity from a multicenter randomized
clinical trial
SO FERTILITY AND STERILITY
LA English
DT Article
DE Insulin resistance; hirsutism; infertility; ovulation induction;
metabolic syndrome
ID QUALITY-OF-LIFE; FEMALE SEXUAL FUNCTION; GENERAL PSYCHOMETRIC
PROPERTIES; BIOLOGIC SPECIMENS REPOSITORY; FERTIQOL TOOL DEVELOPMENT;
FUNCTION INDEX FSFI; SYNDROME PCOS; METABOLIC SYNDROME; DOUBLE-BLIND;
INTERCOURSE COMPLIANCE
AB Objective: To summarize baseline characteristics from a large multicenter infertility clinical trial.
Design: Cross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene).
Setting: Academic Health Centers throughout the United States.
Patient(s): Seven hundred fifty women with polycystic ovary syndrome (PCOS) and their male partners took part in the study.
Intervention(s): None.
Main Outcome Measure(s): Historic, biometric, biochemical, and questionnaire parameters.
Result(s): Females averaged 30 years and were obese (body mass index [BMI] 35) with 20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). Most of the women had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH-to-FSH ratio (2), and antimullerian hormone levels (8.0 ng/mL). In addition, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH-to-FSH levels, antimullerian hormone levels, and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Men were obese (BMI 30) and had normal mean semen parameters.
Conclusion(s): The treatment groups were well matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators.
C1 [Legro, Richard S.] Penn State Univ, Dept Gynecol & Obstet, Hershey, PA USA.
[Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX USA.
[Schlaff, William D.; Alvero, Ruben; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
[Christman, Gregory M.; Ohl, Dana] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Coutifaris, Christos; Barnhart, Kurt T.; Snyder, Peter] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Casson, Peter] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT USA.
[Haisenleder, Daniel J.] Univ Virginia, Ctr Res Reprod, Ligand Core Lab, Charlottesville, VA USA.
[Lucidi, Richard] Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA USA.
[Baker, Valerie] Stanford Hosp, Dept Obstet & Gynecol, Palo Alto, CA USA.
[Usadi, Rebecca] Carolinas HealthCare Ctr Reprod Med, Dept Obstet & Gynecol, Charlotte, NC USA.
[Bates, G. Wright] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
[Trussell, J. C.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Fertil & Infertil Branch, Rockville, MD USA.
[Huang, Hao; Yan, Qingshang; Zhang, Heping] Yale Univ, Sch Med, Dept Biostat, New Haven, CT USA.
RP Legro, RS (reprint author), Penn State Coll Med, Milton S Hershey Med Ctr, Dept Obstet & Gynecol, 500 Univ Dr,H103, Hershey, PA 17033 USA.
EM RSL1@PSU.EDU
OI Diamond, Michael/0000-0001-6353-4489
FU Ohio State University; Yale University; University of Michigan;
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005,
U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, U10 HD055944,
U54-HD29834]; General Clinical Research Center [MO1RR10732, C06
RR016499]
FX R.S.L. reports honorarium from Ferring, Germany for lecture. R. G. B.
has nothing to disclose. M. P. D. reports ASRM Board Membership,
consultancy with Halt Medical, Genzyme, and grants with Abbvie,
Novartis, Boeringher Ingelheim, Ferring, EMD Serono, Biosante. C. C.
reports NOVA Therapeutics Medical Advisory Board, pending grants with
National Institutes of Health (NIH), payment for lectures from Ohio
State University, Yale University, University of Michigan, and
reimbursement for attending Executive Board meetings from ASRM. W. D. S.
has nothing to disclose. R. A. has nothing to disclose. P. C. has
nothing to disclose. G. M. C. has nothing to disclose. H. H. has nothing
to disclose. Q.Y. has nothing to disclose. D.J.H. reports employment
with NIH and pending grants with NIH. K. T. B. has nothing to disclose.
G. W. B. has nothing to disclose. R. U. has nothing to disclose. R. L.
has nothing to disclose. V. B. has nothing to disclose. J.C.T. reports
ownership of equities in Pfizer, Merck, Astellas, J and J. S. A. K. has
nothing to disclose. P. S. has nothing to disclose. D.O. has nothing to
disclose. N.S. has nothing to disclose. E. E. has nothing to disclose.
H.Z. has nothing to disclose.; Supported by NIH/Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) grants
U10 HD27049 (to C. C.), U10 HD38992 (to R. S. L.), U10HD055925 (to
H.Z.), U10 HD39005 (to M. P. D.), U10 HD33172 (to M. P. S.), U10 HD38998
(to W. D. S), U10 HD055936 (to G. M. C.), U10 HD055942 (to R. G. B.),
and U10 HD055944 (to P. R. C.); U54-HD29834 (to the University of
Virginia Center for Research in Reproduction Ligand Assay and Analysis
Core of the Specialized Cooperative Centers Program in Reproduction and
Infertility Research); General Clinical Research Center grants
MO1RR10732 and construction grant C06 RR016499 (to Pennsylvania State
University).
NR 53
TC 13
Z9 13
U1 2
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JAN
PY 2014
VL 101
IS 1
BP 258
EP +
DI 10.1016/j.fertnstert.2013.08.056
PG 20
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 281VJ
UT WOS:000329128800049
PM 24156957
ER
PT S
AU Biesso, A
Xu, JH
Knutson, JR
AF Biesso, Arianna
Xu, Jianhua
Knutson, Jay R.
BE Engelborghs, Y
Visser, AJWG
TI Upconversion Spectrophotofluorometry
SO FLUORESCENCE SPECTROSCOPY AND MICROSCOPY: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Time-resolved fluorescence; Upconversion; Tryptophan; Protein dynamics
and photo-damage
ID TIME-RESOLVED FLUORESCENCE; TRYPTOPHAN FLUORESCENCE; FEMTOSECOND
DYNAMICS; SOLVATION DYNAMICS; BIOLOGICAL WATER; PROTEIN SURFACE;
ENERGY-TRANSFER; PEPTIDE-BOND; PICOSECOND; HYDRATION
AB As the other chapters attest, sensitivity of fluorescent molecules to their local environment has created powerful tools in the study of molecular biology, particularly in the study of protein, DNA, and lipid dynamics. Surprisingly, even events faster than the nanosecond lifetimes of fluorophores are important in protein function, and in particular, events lasting just a few ps reflect on water motion and the coupled dynamics of proteins. These ultrafast phenomena can best be studied by using the same laser that excites fluorescence to also "strobe" the emission, providing sub-picosecond time slices of the action. We explain the strobing "upconversion" technique and some limits on its execution.
C1 [Biesso, Arianna] NIDDK, NIH, Bethesda, MD 20892 USA.
[Xu, Jianhua; Knutson, Jay R.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Biesso, A (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA HL001452-30]
NR 55
TC 0
Z9 0
U1 2
U2 11
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-62703-648-1
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1076
BP 303
EP 319
DI 10.1007/978-1-62703-649-8_12
D2 10.1007/978-1-62703-649-8
PG 17
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Microscopy; Spectroscopy
SC Biochemistry & Molecular Biology; Microscopy; Spectroscopy
GA BJJ01
UT WOS:000328374800013
PM 24108631
ER
PT J
AU Youngren, B
Nielsen, HJ
Jun, S
Austin, S
AF Youngren, Brenda
Nielsen, Henrik Joerk
Jun, Suckjoon
Austin, Stuart
TI The multifork Escherichia coli chromosome is a self-duplicating and
self-segregating thermodynamic ring polymer
SO GENES & DEVELOPMENT
LA English
DT Article
DE bacterial cell cycle; bacterial chromosome; chromosome organization;
chromosome segregation multifork replication
ID SEPARATE CELL HALVES; DIVISION CYCLE; E. COLI; BACTERIAL CHROMOSOME;
REPLICATION; LOCALIZATION; DYNAMICS; FTSK; TERMINUS; PROTEIN
AB At all but the slowest growth rates, Escherichia coli cell cycles overlap, and its nucleoid is segregated to daughter cells as a forked DNA circle with replication ongoing-a state fundamentally different from eukaryotes. We have solved the chromosome organization, structural dynamics, and segregation of this constantly replicating chromosome. It is locally condensed to form a branched donut, compressed so that the least replicated DNA spans the cell center and the newest DNA extends toward the cell poles. Three narrow zones at the cell center and quarters contain both the replication forks and nascent DNA and serve to segregate the duplicated chromosomal information as it flows outward. The overall pattern is smoothly self-replicating, except when the duplicated terminus region is released from the septum and recoils to the center of a sister nucleoid. In circular cross-section of the cell, the left and right arms of the chromosome form separate, parallel structures that lie in each cell half along the radial cell axis. In contrast, replication forks and origin and terminus regions are found mostly at the center of the cross section, balanced by the parallel chromosome arms. The structure is consistent with the model in which the nucleoid is a constrained ring polymer that develops by spontaneous thermodynamics. The ring polymer pattern extrapolates to higher growth rates and also provides a structural basis for the form of the chromosome during very slow growth.
C1 [Youngren, Brenda; Nielsen, Henrik Joerk; Austin, Stuart] NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
[Jun, Suckjoon] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
[Jun, Suckjoon] Univ Calif San Diego, Dept Phys, La Jolla, CA 92093 USA.
RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
EM stuart.austin66@gmail.com
RI Jun, Suckjoon/K-9008-2015
OI Jun, Suckjoon/0000-0002-0139-4297
FU Intramural Program of the National Cancer Institute; Paul G. Allen
Family Foundation; Pew Charitable Trusts; National Science Foundation
CAREER award
FX We thank Youngkyun Jung and Bae-Yeun Ha for supercomputer simulations
data, Sattar Taheri-Araghi for help with time-lapse experiments, and A.
Wright for helpful discussions. This research was supported in part by
the Intramural Program of the National Cancer Institute (S.J.A.), the
Paul G. Allen Family Foundation, the Pew Charitable Trusts, and the
National Science Foundation CAREER award (S.J.).
NR 41
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U1 2
U2 12
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD JAN 1
PY 2014
VL 28
IS 1
BP 71
EP 84
DI 10.1101/gad.231050.113
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 284CK
UT WOS:000329293500008
PM 24395248
ER
PT J
AU Prakash, S
Guo, DC
Maslen, CL
Silberbach, M
Milewicz, D
Bondy, CA
AF Prakash, Siddharth
Guo, Dongchuan
Maslen, Cheryl L.
Silberbach, Michael
Milewicz, Dianna
Bondy, Carolyn A.
CA GenTAC Investigators
TI Single-nucleotide polymorphism array genotyping is equivalent to
metaphase cytogenetics for diagnosis of Turner syndrome
SO GENETICS IN MEDICINE
LA English
DT Article
DE array; cytogenetics; diagnosis; karyotype; sex chromosomes; Turner
syndrome
ID PERIPHERAL-BLOOD LYMPHOCYTES; IDIOPATHIC SHORT STATURE; COPY NUMBER
VARIATION; CHROMOSOME INSTABILITY; MOSAICISM; MECHANISMS; GUIDELINE;
CELLS; RISK
AB Purpose: Turner syndrome is a developmental disorder caused by partial or complete monosomy for the X chromosome in 1 in 2,500 females. We hypothesized that single-nucleotide polymorphism (SNP) array genotyping could provide superior resolution in comparison to metaphase karyotype analysis to facilitate genotype-phenotype correlations.
Methods: We genotyped 187 Turner syndrome patients with 733,000 SNP marker arrays. All cases met diagnostic criteria for Turner syndrome based on karyotypes (60%) or characteristic physical features. The SNP array results confirmed the diagnosis of Turner syndrome in 100% of cases.
Results: We identified a single X chromosome (45, X) in 113 cases. In 58 additional cases (31%), other mosaic cell lines were present, including isochromosomes (16%), rings (5%), and Xp deletions (8%). The remaining cases were mosaic for monosomy X and normal male or female cell lines. Array-based models of X chromosome structure were compatible with karyotypes in 104 of 116 comparable cases (90%). We found that the SNP array data did not detect X-autosome translocations (three cases) but did identify two derivative Y chromosomes and 13 large copy-number variants that were not detected by karyotyping.
Conclusion: Our study is the first systematic comparison between the two methods and supports the utility of SNP array genotyping to address clinical and research questions in Turner syndrome.
C1 [Prakash, Siddharth; Guo, Dongchuan; Milewicz, Dianna] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Houston, TX 77030 USA.
[Maslen, Cheryl L.] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Portland, OR 97201 USA.
[Maslen, Cheryl L.] Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA.
[Silberbach, Michael] Oregon Hlth & Sci Univ, Div Pediat Cardiol, Portland, OR 97201 USA.
[Bondy, Carolyn A.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Prakash, S (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Houston, TX 77030 USA.
EM Siddharth.K.Prakash@uth.tmc.edu
FU Vivian L. Smith Foundation [RO1 HL62594, P50HL083794-01]; Richard T.
Pisani Funds; TexGen Foundation; National Institutes of Health [UL1
RR024148 (CTSA)]; US federal government [HHSN268200648199C,
HHSN268201000048C]; National Heart Lung and Blood Institute (Bethesda,
MD); RTI International (Research Triangle Park, NC); National Institute
of Arthritis and Musculoskeletal and Skin Diseases; Oregon Clinical and
Translational Research Institute (Portland, OR) [UL1 RR024140]; National
Center for Research Resources (Bethesda, MD); Weill Cornell Medical
College Clinical Translational Science Center (New York, NY)
[UL1RR024996]
FX The authors are extremely grateful to patients for providing clinical
data and samples for this study. The following sources provided funding
to D.M.M. for these studies: RO1 HL62594 (D.M.M.), P50HL083794-01
(D.M.M.), Vivian L. Smith Foundation, Richard T. Pisani Funds, and
TexGen Foundation. The National Institutes of Health UL1 RR024148 (CTSA)
grant also provided funds for these studies. The GenTAC Registry has
been supported by US federal government contracts HHSN268200648199C and
HHSN268201000048C from the National Heart Lung and Blood Institute
(Bethesda, MD) with RTI International (Research Triangle Park, NC).
Additional support was provided by the National Institute of Arthritis
and Musculoskeletal and Skin Diseases, the Oregon Clinical and
Translational Research Institute (Portland, OR), grant UL1 RR024140 from
the National Center for Research Resources (Bethesda, MD), and the Weill
Cornell Medical College Clinical Translational Science Center (New York,
NY), grant UL1RR024996.
NR 24
TC 10
Z9 10
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JAN
PY 2014
VL 16
IS 1
BP 53
EP 59
DI 10.1038/gim.2013.77
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 284GO
UT WOS:000329304300008
PM 23743550
ER
PT J
AU Rudolph, KE
Wand, GS
Stuart, EA
Glass, TA
Marques, AH
Duncko, R
Merikangas, KR
AF Rudolph, Kara E.
Wand, Gary S.
Stuart, Elizabeth A.
Glass, Thomas A.
Marques, Andrea H.
Duncko, Roman
Merikangas, Kathleen R.
TI The association between cortisol and neighborhood disadvantage in a US
population-based sample of adolescents
SO HEALTH & PLACE
LA English
DT Article
DE Neighborhood; Adolescents; Cortisol; Propensity; Score
ID SUPPLEMENT NCS-A; PITUITARY-ADRENAL RESPONSES; SALIVARY CORTISOL;
SOCIOECONOMIC-STATUS; PROPENSITY SCORE; SOCIAL STRESS; YOUNG-ADULTS;
LIFE STRESS; HEALTH; CHILDREN
AB The association between neighborhood conditions and corrisol is rarely studied in children or adolescents and has been hampered by small sample size and racial/ethnic and geographic homogeneity. Our objective was to estimate the association between neighborhood disadvantage and salivary cortisol levels in a large, geographically and racially/ethnically diverse sample of adolescents from the National Comorbidity Survey Replication Adolescent Supplement. Salivary cortisol was collected before and after an interview administered in the adolescent's home. We used a propensity score approach to match adolescents living in disadvantaged neighborhoods with those in non-disadvantaged neighborhoods to create two similar groups based on the time and day of cortisol collection as well as demographic characteristics. Adolescents living in disadvantaged neighborhoods had higher pre-interview cortisol levels and steeper rates of decline in cortisol levels over the course of the interview than similar adolescents in non-disadvantaged neighborhoods. This bolsters the evidence base suggesting that place may influence the stress response system. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Rudolph, Kara E.; Glass, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Rudolph, Kara E.; Stuart, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
[Wand, Gary S.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21287 USA.
[Stuart, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.
[Marques, Andrea H.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Marques, Andrea H.; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Duncko, Roman] South London & Maudsley NHS Fdn Trust, London, England.
RP Rudolph, KE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6144, Baltimore, MD 21205 USA.
EM krudolph@jhsph.edu; gwand@jhmi.edu; estuart@jhsph.edu; tglass@jhsph.edu;
andreahorvathmarques@gmail.com; roman.duncko@gmail.com;
merikank@mail.nih.gov
OI Stuart, Elizabeth/0000-0002-9042-8611; Glass, Thomas/0000-0003-4399-612X
FU Intramural Research Program of the National Institute of Mental Health
at the National Institutes of Health (NIH) [Z01 MH-002808-08]; NIH
[K05AA02034]; National Institute of Mental Health [U01-MH60220];
National Institute of Drug Abuse at the NIH [R01 DA016558]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health at the National Institutes of Health
(NIH) [Z01 MH-002808-08]. GSW's time was supported by NIH grant
K05AA02034. The National Comorbidity Survey Replication Adolescent
Supplement (NCS-A) and the larger program of related National
Comorbidity Surveys are supported by the National Institute of Mental
Health [U01-MH60220] and the National Institute of Drug Abuse [R01
DA016558] at the NIH. The NCS-A was carried out in conjunction with the
World Health Organization World Mental Health Survey Initiative. The
authors wish to thank Vanya Aggarwal for help with Census data
abstraction.
NR 71
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U1 6
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8292
EI 1873-2054
J9 HEALTH PLACE
JI Health Place
PD JAN
PY 2014
VL 25
BP 68
EP 77
DI 10.1016/j.healthplace.2013.11.001
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 280WB
UT WOS:000329060400009
PM 24367996
ER
PT J
AU Alter, HJ
AF Alter, Harvey J.
TI The Road Not Taken or How I Learned to Love the Liver: A Personal
Perspective on Hepatitis History
SO HEPATOLOGY
LA English
DT Editorial Material
ID NON-B-HEPATITIS; TRANSFUSION-TRANSMITTED VIRUSES; NON-A-HEPATITIS;
POSTTRANSFUSION HEPATITIS; BLOOD-DONORS; C VIRUS; ANTIGEN; RECIPIENTS;
ANTIBODY; TRANSMISSION
C1 [Alter, Harvey J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Alter, HJ (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bldg 10,Room 1C-711,10 Ctr Dr, Bethesda, MD 20892 USA.
EM HAlter@cc.nih.gov
NR 21
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2014
VL 59
IS 1
BP 4
EP 12
DI 10.1002/hep.26787
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 276GZ
UT WOS:000328738400001
PM 24123147
ER
PT J
AU Cinar, R
Godlewski, G
Liu, J
Tam, J
Jourdan, T
Mukhopadhyay, B
Harvey-White, J
Kunos, G
AF Cinar, Resat
Godlewski, Grzegorz
Liu, Jie
Tam, Joseph
Jourdan, Tony
Mukhopadhyay, Bani
Harvey-White, Judith
Kunos, George
TI Hepatic Cannabinoid-1 Receptors Mediate Diet-Induced Insulin Resistance
by Increasing De Novo Synthesis of Long-Chain Ceramides
SO HEPATOLOGY
LA English
DT Article
ID SKELETAL-MUSCLE CELLS; KINASE-C-ZETA; SERINE-PALMITOYLTRANSFERASE;
SPHINGOLIPID METABOLISM; PROTEIN PHOSPHATASE-2A; LEPTIN RESISTANCE;
OBESE SUBJECTS; CB1 RECEPTORS; RISK-FACTORS; INHIBITION
AB Obesity is associated with increased activity of two lipid signaling systems (endocannabinoids [ECs] and ceramides), with both being implicated in insulin resistance. Cannabinoid-1 receptor (CB1R) antagonists reverse obesity and insulin resistance, but have psychiatric side effects. Here we analyzed the role of ceramide in CB1R-mediated insulin resistance in C57Bl6/J mice with high-fat diet-induced obesity (DIO), using JD5037, a peripherally restricted CB1R inverse agonist. Chronic JD5037 treatment of DIO mice reduced body weight and steatosis and improved glucose tolerance and insulin sensitivity. Peripheral CB1R blockade also attenuated the diet-induced increase in C14:0, C16:0, C18:0, and C20:0 ceramide species with either C16 or C18 sphingosine-base in the liver. Decreased ceramide levels reflected their reduced de novo synthesis, due to inhibition of the activity of serine-palmitoyl transferase (SPT) and the expression of its SPTLC3 catalytic subunit, as well as reduced ceramide synthase (CerS) activity related to reduced expression of CerS1 and CerS6. JD5037 treatment also increased ceramide degradation due to increased expression of ceramidases. In primary cultured mouse hepatocytes and HepG2 cells, the EC anandamide increased ceramide synthesis in an eIF2-dependent manner, and inhibited insulin-induced akt phosphorylation by increased serine phosphorylation of IRS1 and increased expression of the serine/threonine phosphatase Phlpp1. These effects were abrogated by JD5037 or the SPT inhibitor myriocin. Chronic treatment of DIO mice with myriocin or JD5037 similarly reversed hepatic insulin resistance, as verified using a euglycemic/hyperinsulinemic clamp. Conclusion: ECs induce CB1R-mediated, endoplasmic reticulum stress-dependent synthesis of specific ceramide subspecies in the liver, which plays a key role in obesity-related hepatic insulin resistance. (Hepatology 2014;58:143-153)
C1 [Cinar, Resat; Godlewski, Grzegorz; Liu, Jie; Tam, Joseph; Jourdan, Tony; Mukhopadhyay, Bani; Harvey-White, Judith; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
EM cinarr@mail.nih.gov; George.Kunos@nih.gov
OI CINAR, RESAT/0000-0002-8597-7253
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health
FX Supported by Intramural funds from the National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health.
NR 47
TC 34
Z9 37
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JAN
PY 2014
VL 59
IS 1
BP 143
EP 153
DI 10.1002/hep.26606
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 276GZ
UT WOS:000328738400018
PM 23832510
ER
PT J
AU Ozel, AB
Moroi, SE
Reed, DM
Nika, M
Schmidt, CM
Akbari, S
Scott, K
Rozsa, F
Pawar, H
Musch, DC
Lichter, PR
Gaasterland, D
Branham, K
Gilbert, J
Garnai, SJ
Chen, W
Othman, M
Heckenlively, J
Swaroop, A
Abecasis, G
Friedman, DS
Zack, D
Ashley-Koch, A
Ulmer, M
Kang, JH
Liu, YT
Yaspan, BL
Haines, J
Allingham, RR
Hauser, MA
Pasquale, L
Wiggs, J
Richards, JE
Li, JZ
AF Ozel, A. Bilge
Moroi, Sayoko E.
Reed, David M.
Nika, Melisa
Schmidt, Caroline M.
Akbari, Sara
Scott, Kathleen
Rozsa, Frank
Pawar, Hemant
Musch, David C.
Lichter, Paul R.
Gaasterland, Doug
Branham, Kari
Gilbert, Jesse
Garnai, Sarah J.
Chen, Wei
Othman, Mohammad
Heckenlively, John
Swaroop, Anand
Abecasis, Goncalo
Friedman, David S.
Zack, Don
Ashley-Koch, Allison
Ulmer, Megan
Kang, Jae H.
Liu, Yutao
Yaspan, Brian L.
Haines, Jonathan
Allingham, R. Rand
Hauser, Michael A.
Pasquale, Louis
Wiggs, Janey
Richards, Julia E.
Li, Jun Z.
CA NEIGHBOR Consortium
TI Genome-wide association study and meta-analysis of intraocular pressure
SO HUMAN GENETICS
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; CENTRAL CORNEAL THICKNESS; TO-DISC RATIO; MACULAR
DEGENERATION; MOLECULAR-BIOLOGY; GENETIC-VARIANTS; RISK-FACTORS;
HERITABILITY; EYE; POPULATION
AB Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in > 6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 x 10(-8)). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.
C1 [Ozel, A. Bilge; Li, Jun Z.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Moroi, Sayoko E.; Reed, David M.; Nika, Melisa; Schmidt, Caroline M.; Akbari, Sara; Scott, Kathleen; Rozsa, Frank; Pawar, Hemant; Musch, David C.; Lichter, Paul R.; Branham, Kari; Gilbert, Jesse; Garnai, Sarah J.; Othman, Mohammad; Heckenlively, John; Richards, Julia E.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Musch, David C.; Richards, Julia E.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Gaasterland, Doug] Eye Doctors Washington DC, Washington, DC USA.
[Chen, Wei] Univ Pittsburgh, Childrens Hosp Pittsburgh, Sch Med, Div Pulm Med Allergy & Immunol, Pittsburgh, PA USA.
[Chen, Wei] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA.
[Chen, Wei] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA.
[Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA.
[Abecasis, Goncalo] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Friedman, David S.; Zack, Don] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Ashley-Koch, Allison; Ulmer, Megan; Liu, Yutao; Allingham, R. Rand; Hauser, Michael A.] Duke Univ, Sch Med, Ctr Human Genet, Durham, NC USA.
[Kang, Jae H.; Pasquale, Louis] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Yaspan, Brian L.; Haines, Jonathan] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA.
[Pasquale, Louis; Wiggs, Janey] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Li, JZ (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
EM smoroi@med.umich.edu; junzli@med.umich.edu
OI Rozsa, Frank/0000-0002-1378-7020; Reed, David/0000-0002-4772-6138;
Carnes, Megan/0000-0002-7270-132X; Zack, Don/0000-0002-7966-1973;
Swaroop, Anand/0000-0002-1975-1141; Ashley-Koch,
Allison/0000-0001-5409-9155
FU University of Michigan Glaucoma Research Center; Ellison Medical
Foundation; Harvard Glaucoma Center for Excellence; Margolis Fund;
Research to Prevent Blindness; Glaucoma Research Foundation; Glaucoma
Foundation; American Health Assistance Foundation; Elmer and Silvia
Sramek Foundation; Foundation Fighting Blindness; Macula Vision Research
Foundation; Pew Charitable Trusts; Casey Macular Degeneration Center
Fund; Marion W. and Edward F. Knight AMD Fund; Harold and Pauline Price
Foundation; National Genotyping Centre of Spain
FX Other supports included funding from University of Michigan Glaucoma
Research Center (S. E. M., J.E.R., J.Z.L.); Ellison Medical Foundation
(J.Z.L.); Harvard Glaucoma Center for Excellence, and the Margolis Fund
(J.W. and L. P.); Research to Prevent Blindness (A. S., D. C. M., J.W.,
L. P., J.R.H., and J.E.R.); the Glaucoma Research Foundation (S. E. M.,
Y.L.); the Glaucoma Foundation (Y.L.); American Health Assistance
Foundation (Y.L., J.E.R., J.R.H., A. S.); Elmer and Silvia Sramek
Foundation (J.R.H., A. S.); Foundation Fighting Blindness (J.R.H., A.
S.); the Macula Vision Research Foundation (J.R.H., A. S.); the Pew
Charitable Trusts (J.R.H., A. S.); the Casey Macular Degeneration Center
Fund (J.R.H., A. S.); the Marion W. and Edward F. Knight AMD Fund
(J.R.H., A. S.); the Harold and Pauline Price Foundation, National
Genotyping Centre of Spain (J.R.H., A.S.).
NR 50
TC 30
Z9 30
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD JAN
PY 2014
VL 133
IS 1
BP 41
EP 57
DI 10.1007/s00439-013-1349-5
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 283KH
UT WOS:000329244500004
PM 24002674
ER
PT J
AU Shameer, K
Denny, JC
Ding, KY
Jouni, H
Crosslin, DR
de Andrade, M
Chute, CG
Peissig, P
Pacheco, JA
Li, RL
Bastarache, L
Kho, AN
Ritchie, MD
Masys, DR
Chisholm, RL
Larson, EB
McCarty, CA
Roden, DM
Jarvik, GP
Kullo, IJ
AF Shameer, Khader
Denny, Joshua C.
Ding, Keyue
Jouni, Hayan
Crosslin, David R.
de Andrade, Mariza
Chute, Christopher G.
Peissig, Peggy
Pacheco, Jennifer A.
Li, Rongling
Bastarache, Lisa
Kho, Abel N.
Ritchie, Marylyn D.
Masys, Daniel R.
Chisholm, Rex L.
Larson, Eric B.
McCarty, Catherine A.
Roden, Dan M.
Jarvik, Gail P.
Kullo, Iftikhar J.
TI A genome- and phenome-wide association study to identify genetic
variants influencing platelet count and volume and their pleiotropic
effects
SO HUMAN GENETICS
LA English
DT Article
ID ELECTRONIC MEDICAL-RECORDS; BLOOD-PRESSURE; ANKYLOSING-SPONDYLITIS;
MYOCARDIAL-INFARCTION; DISEASE ASSOCIATIONS; METASTASIS; PATHWAYS; RISK;
PHEWAS; HUMANS
AB Platelets are enucleated cell fragments derived from megakaryocytes that play key roles in hemostasis and in the pathogenesis of atherothrombosis and cancer. Platelet traits are highly heritable and identification of genetic variants associated with platelet traits and assessing their pleiotropic effects may help to understand the role of underlying biological pathways. We conducted an electronic medical record (EMR)-based study to identify common variants that influence inter-individual variation in the number of circulating platelets (PLT) and mean platelet volume (MPV), by performing a genome-wide association study (GWAS). We characterized genetic variants associated with MPV and PLT using functional, pathway and disease enrichment analyses; we assessed pleiotropic effects of such variants by performing a phenome-wide association study (PheWAS) with a wide range of EMR-derived phenotypes. A total of 13,582 participants in the electronic MEdical Records and GEnomic network had data for PLT and 6,291 participants had data for MPV. We identified five chromosomal regions associated with PLT and eight associated with MPV at genome-wide significance (P < 5E-8). In addition, we replicated 20 SNPs [out of 56 SNPs (alpha: 0.05/56 = 9E-4)] influencing PLT and 22 SNPs [out of 29 SNPs (alpha: 0.05/29 = 2E-3)] influencing MPV in a published meta-analysis of GWAS of PLT and MPV. While our GWAS did not find any new associations, our functional analyses revealed that genes in these regions influence thrombopoiesis and encode kinases, membrane proteins, proteins involved in cellular trafficking, transcription factors, proteasome complex subunits, proteins of signal transduction pathways, proteins involved in megakaryocyte development, and platelet production and hemostasis. PheWAS using a single-SNP Bonferroni correction for 1,368 diagnoses (0.05/1368 = 3.6E-5) revealed that several variants in these genes have pleiotropic associations with myocardial infarction, autoimmune, and hematologic disorders. We conclude that multiple genetic loci influence interindividual variation in platelet traits and also have significant pleiotropic effects; the related genes are in multiple functional pathways including those relevant to thrombopoiesis.
C1 [Shameer, Khader; Ding, Keyue; Jouni, Hayan; Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA.
[Denny, Joshua C.; Bastarache, Lisa] Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA.
[Denny, Joshua C.; Bastarache, Lisa] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA.
[Crosslin, David R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[de Andrade, Mariza; Chute, Christopher G.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Peissig, Peggy] Marshfield Clin Fdn Med Res & Educ, Biomed Informat Res Ctr, Marshfield, WI 54449 USA.
[Pacheco, Jennifer A.; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Li, Rongling] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Kho, Abel N.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Ritchie, Marylyn D.] Penn State Univ, Eberly Coll Sci, Huck Inst Life Sci, Ctr Syst Genom, University Pk, PA 16802 USA.
[Masys, Daniel R.] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA.
[Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[McCarty, Catherine A.] Essentia Inst Rural Hlth, Duluth, MN 55805 USA.
[Roden, Dan M.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA.
[Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Kullo, IJ (reprint author), Mayo Clin, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA.
EM kullo.iftikhar@mayo.edu
RI Jarvik, Gail/N-6476-2014; Khader, Shameer/J-2564-2016;
OI Jarvik, Gail/0000-0002-6710-8708; Pacheco, Jennifer/0000-0001-8021-5818
FU National Human Genome Research Institute (NHGRI); National Institute of
General Medical Sciences (NIGMS) [U01-HG-04599, U01-HG-004610,
UO1-AG-06781, U01-HG-004608, U01HG004609, U01-HG-04603]; Washington
State Life Sciences Discovery Fund award; [R01-LM-010685]
FX The eMERGE network was initiated and funded by the National Human Genome
Research Institute (NHGRI), with additional funding from National
Institute of General Medical Sciences (NIGMS) through the following
grants: U01-HG-04599 (Mayo Clinic); U01-HG-004610 and UO1-AG-06781
(Group Health Cooperative); U01-HG-004608 (Marshfield Clinic);
U01HG004609 (Northwestern University); and U01-HG-04603 (Vanderbilt
University, also serving as the Administrative Coordinating Center). We
also acknowledge the genotyping centers U01-HG-004424 (Broad Institute)
and U01-HG-004438 (Johns Hopkins University, Center for Inherited
Disease Research). Additional genotyping support was provided by a
Washington State Life Sciences Discovery Fund award to the Northwest
Institute of Genetic Medicine (G.P.J). Additional support for PheWAS was
provided through R01-LM-010685.
NR 84
TC 38
Z9 40
U1 1
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD JAN
PY 2014
VL 133
IS 1
BP 95
EP 109
DI 10.1007/s00439-013-1355-7
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 283KH
UT WOS:000329244500008
PM 24026423
ER
PT J
AU Gearhart, PJ
Kelsoe, G
AF Gearhart, Patricia J.
Kelsoe, Garnett
TI A tribute to Michael S. Neuberger Obituary
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Biographical-Item
C1 [Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
[Kelsoe, Garnett] Duke Univ, Dept Immunol, Durham, NC USA.
[Kelsoe, Garnett] Duke Univ, Human Vaccine Inst, Durham, NC USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN
PY 2014
VL 124
IS 1
BP 3
EP 5
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 284PX
UT WOS:000329333500002
PM 24382382
ER
PT J
AU El Touny, LH
Vieira, A
Mendoza, A
Khanna, C
Hoenerhoff, MJ
Green, JE
AF El Touny, Lara H.
Vieira, Anthony
Mendoza, Arnulfo
Khanna, Chand
Hoenerhoff, Mark J.
Green, Jeffrey E.
TI Combined SFK/MEK inhibition prevents metastatic outgrowth of dormant
tumor cells
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID BREAST-CANCER CELLS; MOUSE MAMMARY-TUMOR; PHASE-II TRIAL; C-SRC;
3-DIMENSIONAL CULTURE; EXTRACELLULAR-MATRIX; BONE METASTASIS;
KINASE-ACTIVITY; DOWN-REGULATION; POOR-PROGNOSIS
AB Breast cancer (BC) can recur as metastatic disease many years after primary tumor removal, suggesting that disseminated tumor cells survive for extended periods in a dormant state that is refractory to conventional therapies. We have previously shown that altering the tumor microenvironment through fibrosis with collagen and fibronectin deposition can trigger tumor cells to switch from a dormant to a proliferative state. Here, we used an in vivo preclinical model and a 3D in vitro model of dormancy to evaluate the role of Src family kinase (SFK) in regulating this dormant-to-proliferative switch. We found that pharmacological inhibition of SFK signaling or Src knockdown results in the nuclear localization of cyclin-dependent kinase inhibitor p27 and prevents the proliferative outbreak of dormant BC cells and metastatic lesion formation; however, SFK inhibition did not kill dormant cells. Dormant cell proliferation also required ERK1/2 activation. Combination treatment of cells undergoing the dormant-to-proliferative switch with the Src inhibitor (AZD0530) and MEK1/2 inhibitor (AZD6244) induced apoptosis in a large fraction of the dormant cells and delayed metastatic outgrowth, neither of which was observed with either inhibitor alone. Thus, targeting Src prevents the proliferative response of dormant cells to external stimuli, but requires MEK1/2 inhibition to suppress their survival. These data indicate that treatments targeting Src in combination with MEK1/2 may prevent BC recurrence.
C1 [El Touny, Lara H.; Vieira, Anthony; Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Mendoza, Arnulfo; Khanna, Chand] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Hoenerhoff, Mark J.] NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
RP Green, JE (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37,Room 4054,37 Convent Dr, Bethesda, MD 20892 USA.
EM jegreen@nih.gov
FU NIH; CCR; NCI
FX This work was supported by the Intramural Research Program of the NIH,
CCR, and NCI. We thank Glenn Merlino, Stuart Yuspa, Peter Blumberg, and
Olga Aprelikova for useful discussions; Julie Foley and Norris Flagler
for the collagen image analysis; and the Laboratory Animal Science
Program and the FACS core facility at the NCI for excellent technical
assistance.
NR 51
TC 23
Z9 24
U1 1
U2 22
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN
PY 2014
VL 124
IS 1
BP 156
EP 168
DI 10.1172/JCI70259
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 284PX
UT WOS:000329333500025
PM 24316974
ER
PT J
AU Terunuma, A
Putluri, N
Mishra, P
Mathe, EA
Dorsey, TH
Yi, M
Wallace, TA
Issaq, HJ
Zhou, M
Killian, JK
Stevenson, HS
Karoly, ED
Chan, K
Samanta, S
Prieto, D
Hsu, TYT
Kurley, SJ
Putluri, V
Sonavane, R
Edelman, DC
Wulff, J
Starks, AM
Yang, YM
Kittles, RA
Yfantis, HG
Lee, DH
Loffe, OB
Schiff, R
Stephens, RM
Meltzer, PS
Veenstra, TD
Westbrook, TF
Sreekumar, A
Ambs, S
AF Terunuma, Atsushi
Putluri, Nagireddy
Mishra, Prachi
Mathe, Ewy A.
Dorsey, Tiffany H.
Yi, Ming
Wallace, Tiffany A.
Issaq, Haleem J.
Zhou, Ming
Killian, J. Keith
Stevenson, Holly S.
Karoly, Edward D.
Chan, King
Samanta, Susmita
Prieto, DaRue
Hsu, Tiffany Y. T.
Kurley, Sarah J.
Putluri, Vasanta
Sonavane, Rajni
Edelman, Daniel C.
Wulff, Jacob
Starks, Adrienne M.
Yang, Yinmeng
Kittles, Rick A.
Yfantis, Harry G.
Lee, Dong H.
Loffe, Olga B.
Schiff, Rachel
Stephens, Robert M.
Meltzer, Paul S.
Veenstra, Timothy D.
Westbrook, Thomas F.
Sreekumar, Arun
Ambs, Stefan
TI MYC-driven accumulation of 2-hydroxyglutarate is associated with breast
cancer prognosis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GENE-EXPRESSION SIGNATURE; HYDROXYACID-OXOACID TRANSHYDROGENASE;
GLUTAMINE-METABOLISM; MOLECULAR PORTRAITS; ALPHA-KETOGLUTARATE;
MASS-SPECTROMETRY; C-MYC; IDH1; METHYLATION; PROGRESSION
AB Metabolic profiling of cancer cells has recently been established as a promising tool for the development of therapies and identification of cancer biomarkers. Here we characterized the metabolomic profile of human breast tumors and uncovered intrinsic metabolite signatures in these tumors using an untargeted discovery approach and validation of key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human breast cancer cell lines. We discovered an association between increased 2HG levels and MYC pathway activation in breast cancer, and further corroborated this relationship using MYC overexpression and knockdown in human mammary epithelial and breast cancer cells. Further analyses revealed globally increased DNA methylation in 2HG-high tumors and identified a tumor subtype with high tissue 2HG and a distinct DNA methylation pattern that was associated with poor prognosis and occurred with higher frequency in African-American patients. Tumors of this subtype had a stem cell-like transcriptional signature and tended to overexpress glutaminase, suggestive of a functional relationship between glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our findings implicate 2HG as a candidate breast cancer oncometabolite associated with MYC activation and poor prognosis.
C1 [Terunuma, Atsushi; Mishra, Prachi; Mathe, Ewy A.; Dorsey, Tiffany H.; Wallace, Tiffany A.; Starks, Adrienne M.; Yang, Yinmeng; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Putluri, Nagireddy; Samanta, Susmita; Hsu, Tiffany Y. T.; Kurley, Sarah J.; Putluri, Vasanta; Sonavane, Rajni; Westbrook, Thomas F.; Sreekumar, Arun] Baylor Coll Med, Alkek Ctr Mol Discovery, Verna & Marrs Mclean Dept Biochem, Dept Mol & Cell Biol, Houston, TX 77030 USA.
[Yi, Ming; Stephens, Robert M.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA.
[Issaq, Haleem J.; Zhou, Ming; Chan, King; Prieto, DaRue; Veenstra, Timothy D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Frederick, MD USA.
[Killian, J. Keith; Stevenson, Holly S.; Edelman, Daniel C.; Meltzer, Paul S.] NCI, Genet Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Karoly, Edward D.; Wulff, Jacob] Metabolon Inc, Durham, NC USA.
[Kittles, Rick A.] Univ Illinois, Coll Med, Chicago, IL USA.
[Yfantis, Harry G.; Lee, Dong H.] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA.
[Loffe, Olga B.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Schiff, Rachel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Schiff, Rachel] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA.
[Killian, J. Keith; Stevenson, Holly S.; Edelman, Daniel C.; Meltzer, Paul S.] NCI, Clin Mol Profiling Core, NIH, Bethesda, MD 20892 USA.
RP Ambs, S (reprint author), NCI, Bldg 37,Room 3050B, Bethesda, MD 20892 USA.
EM Arun.Sreekumar@bcm.edu; ambss@mail.nih.gov
FU Intramural Research Program of the NIH; NCI; CCR; NCI Director's
Innovation Award; NIH SPORE [CA58183]; Susan Komen Foundation [KG110818,
U01 CA167234, DMS-1161759, RP120092]; Alkek,Center for Molecular
Discovery; [1RO1CA133458-01]
FX This research was supported by the Intramural Research Program of the
NIH, NCI, CCR and by a NCI Director's Innovation Award to S. Ambs. A.
Sreekumar acknowledges the following grant support: 1RO1CA133458-01, NIH
SPORE CA58183, Susan Komen Foundation grant KG110818, U01 CA167234,
DMS-1161759, RP120092, and funds from the Alkek,Center for Molecular
Discovery (ASK). The authors thank Raymond Jones, Audrey Salabes, Leoni
Leondaridis, Glennwood Trivers, Elise Bowman, and personnel at the
University of Maryland and the Baltimore Veterans Administration and the
Surgery and Pathology Departments at the University of Maryland Medical
Center, Baltimore Veterans Affairs Medical Center, Union Memorial
Hospital, Mercy Medical Center, and Sinai Hospital for their
contributions in patient recruitment.
NR 70
TC 81
Z9 81
U1 1
U2 21
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN
PY 2014
VL 124
IS 1
BP 398
EP 412
DI 10.1172/JCI71180
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 284PX
UT WOS:000329333500045
PM 24316975
ER
PT J
AU Cousins, MM
Konikoff, J
Laeyendecker, O
Celum, C
Buchbinder, SP
Seage, GR
Kirk, GD
Moore, RD
Mehta, SH
Margolick, JB
Brown, J
Mayer, KH
Koblin, BA
Wheeler, D
Justman, JE
Hodder, SL
Quinn, TC
Brookmeyer, R
Eshleman, SH
AF Cousins, Matthew M.
Konikoff, Jacob
Laeyendecker, Oliver
Celum, Connie
Buchbinder, Susan P.
Seage, George R., III
Kirk, Gregory D.
Moore, Richard D.
Mehta, Shruti H.
Margolick, Joseph B.
Brown, Joelle
Mayer, Kenneth H.
Koblin, Beryl A.
Wheeler, Darrell
Justman, Jessica E.
Hodder, Sally L.
Quinn, Thomas C.
Brookmeyer, Ron
Eshleman, Susan H.
TI HIV Diversity as a Biomarker for HIV Incidence Estimation: Including a
High-Resolution Melting Diversity Assay in a Multiassay Algorithm
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID UNITED-STATES; VACCINE PREPAREDNESS; INCIDENCE RATES; COHORT; INFECTION;
TRIALS; SEROCONVERSION; IMMUNOASSAY; NETWORK; PLASMA
AB Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.
C1 [Cousins, Matthew M.; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Konikoff, Jacob; Brookmeyer, Ron] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Moore, Richard D.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Celum, Connie] Univ Washington, Dept Med, Seattle, WA USA.
[Buchbinder, Susan P.] San Francisco Dept Hlth, Bridge HIV, San Francisco, CA USA.
[Buchbinder, Susan P.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Buchbinder, Susan P.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kirk, Gregory D.; Mehta, Shruti H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Margolick, Joseph B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Brown, Joelle] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Fenway Inst, Boston, MA 02215 USA.
[Koblin, Beryl A.] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA.
[Wheeler, Darrell] Loyola Univ Chicago, Grad Sch Social Work, Chicago, IL USA.
[Justman, Jessica E.] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Justman, Jessica E.] Columbia Univ, Dept Med, New York, NY USA.
[Hodder, Sally L.] Rutgers State Univ, Dept Med, Div Infect Dis, Newark, NJ 07102 USA.
RP Eshleman, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
EM seshlem@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU HIV Prevention Trials Network (HPTN); National Institute of Allergy and
Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA);
National Institute of Mental Health; Office of AIDS Research of the
National Institutes of Health (NIH), Department of Health and Human
Services [UM1-AI068613]; Division of Intramural Research, NIAID, NIH;
HIVNET 001/001.1 [N01-AI35176, N01-AI-45200, AI-45202]; ALIVE
[R01-DA-04334, R01-DA12568]; MACS [U01-AI35042, U01-AI35043,
U01-AI35039, U01-AI35040, U01-AI35041, UL1-RR025005]; JHHCC
[R01-DA011602, R01-AA016893]; [R01-AI095068]; [UM1-AI068619];
[UM1-AI068617]
FX We thank the study teams and participants who provided the samples and
data for this work. We also thank the laboratory staff at Johns Hopkins
University for their technical support and Deborah Donnell for her
helpful discussions. This work was supported by: the HIV Prevention
Trials Network (HPTN), sponsored by the National Institute of Allergy
and Infectious Diseases (NIAID), the National Institute on Drug Abuse
(NIDA), the National Institute of Mental Health, and the Office of AIDS
Research of the National Institutes of Health (NIH), Department of
Health and Human Services (grant no. UM1-AI068613 to S. H. E.).
Additional funding was provided by grant no. R01-AI095068 (to S. H. E.
and R. B.) and the Division of Intramural Research, NIAID, NIH. Support
for the studies that provided samples for this project are as follows:
from HIVNET 001/001.1, grant no. N01-AI35176, N01-AI-45200, and
AI-45202; from ALIVE, grant no. R01-DA-04334 and R01-DA12568; from MACS,
grant no. U01-AI35042, U01-AI35043, U01-AI35039, U01-AI35040,
U01-AI35041, and UL1-RR025005; from JHHCC, grant no. R01-DA011602 and
R01-AA016893 to R. D. M.; and from HPTN 061 and HPTN 064, grant no.
UM1-AI068619, UM1-AI068617, and UM1-AI068613. The funders had no role in
the design or conduct of the study, data collection or analysis,
preparation of the manuscript, or the decision to publish.
NR 36
TC 10
Z9 10
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JAN
PY 2014
VL 52
IS 1
BP 115
EP 121
DI 10.1128/JCM.02040-13
PG 7
WC Microbiology
SC Microbiology
GA 283CM
UT WOS:000329222400019
PM 24153134
ER
PT J
AU Sahasrabuddhe, VV
Gravitt, PE
Dunn, ST
Brown, D
Allen, RA
Eby, YJ
Smith, K
Zuna, RE
Zhang, RR
Gold, MA
Schiffman, M
Walker, JL
Castle, PE
Wentzensen, N
AF Sahasrabuddhe, Vikrant V.
Gravitt, Patti E.
Dunn, S. Terence
Brown, David
Allen, Richard A.
Eby, Yolanda J.
Smith, Katie
Zuna, Rosemary E.
Zhang, Roy R.
Gold, Michael A.
Schiffman, Mark
Walker, Joan L.
Castle, Philip E.
Wentzensen, Nicolas
TI Comparison of Human Papillomavirus Detections in Urine, Vulvar, and
Cervical Samples from Women Attending a Colposcopy Clinic
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID VAGINAL HUMAN-PAPILLOMAVIRUS; HPV-DNA DETECTION; PAIRED URINE; CANCER;
PCR; POPULATION; PREVALENCE; PREVENTION; INFECTION; SPECIMENS
AB While urine-based sampling for human papillomavirus (HPV) is being explored as a simple and noninvasive approach for cervical cancer screening, data comparing HPV genotyping in urine and those in cellular sampling of the cervix and vulva, and their correlation with rigorously confirmed cervical disease status, are sparse. We performed HPV genotyping on voided-urine and clinician-collected vulvar and cervical samples from 72 women undergoing colposcopy. Although urine-based HPV carcinogenic HPV detection was lower (58.3%) than cervical (73.6%) and vulvar (72.1%) detection (P = 0.05 and 0.07, respectively), the agreement of urine HPV with cervical and vulvar HPV was moderate (kappa = 0.55) and substantial (kappa = 0.62), respectively. Urine-based carcinogenic HPV detection had a clinical sensitivity of 80.8% (95% confidence interval [CI] = 60.7 to 93.5) and a specificity of 53.3% (95% CI = 37.9 to 68.3) for diagnosing cervical intraepithelial neoplasia grades 2/3 (CIN2/3) on histology; 90.0% of CIN3 was positive for urine HPV. The corresponding sensitivity and specificity values for vulvar sampling were 92% (95% CI = 74 to 99) and 40.5% (95% CI = 25.6 to 56.7), and those for cervical sampling were 96.2% (95% CI = 80.4 to 99.9) and 40% (95% CI = 25.7 to 55.7), respectively. HPV16 was the most common carcinogenic genotype detectable in 25% of urine, 33.8% of vulvar, and 31.9% of cervical samples overall, with prevalence increasing with cervical disease grade, regardless of the sampling method. Stronger cervical HPV PCR signal strengths were associated with increased frequency of urine HPV detection. In summary, the relatively lower detection rates but comparable clinical performance of urine-based HPV sampling underscore the need for larger studies to evaluate urine-based sampling for cervical cancer screening, epidemiologic studies, and postvaccination HPV disease surveillance.
C1 [Sahasrabuddhe, Vikrant V.; Schiffman, Mark; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Gravitt, Patti E.; Eby, Yolanda J.; Walker, Joan L.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
[Dunn, S. Terence; Brown, David; Allen, Richard A.; Smith, Katie; Zuna, Rosemary E.; Zhang, Roy R.; Gold, Michael A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Castle, Philip E.] Global Canc Initiat, Chestertown, MD USA.
RP Sahasrabuddhe, VV (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
EM vikrant.sahasrabuddhe@nih.gov
FU National Cancer Institute at the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute at the National Institutes of Health.
NR 30
TC 7
Z9 7
U1 0
U2 15
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JAN
PY 2014
VL 52
IS 1
BP 187
EP 192
DI 10.1128/JCM.01623-13
PG 6
WC Microbiology
SC Microbiology
GA 283CM
UT WOS:000329222400028
PM 24197879
ER
PT J
AU Gupta, GN
Benson, JS
Ross, MJ
Sundaram, VS
Lin, KY
Pinto, PA
Linehan, WM
Bratslavsky, G
AF Gupta, Gopal N.
Benson, Jonas S.
Ross, Michael J.
Sundaram, Vani S.
Lin, Kelly Y.
Pinto, Peter A.
Linehan, W. Marston
Bratslavsky, Gennady
TI Perioperative, Functional, and Oncologic Outcomes of Partial
Adrenalectomy for Multiple Ipsilateral Pheochromocytomas
SO JOURNAL OF ENDOUROLOGY
LA English
DT Article
ID FOLLOW-UP; HISTORY
AB Objective: Managing patients with multiple adrenal masses is technically challenging. We present our experience with minimally invasive partial adrenalectomy (PA) performed for synchronous multiple ipsilateral pheochromocytomas in a single setting. Materials and Methods: We reviewed records of patients undergoing PA for pheochromocytoma at the National Cancer Institute between 1994 and 2010. Patients were included if multiple tumors were excised from the ipsilateral adrenal gland in the same operative setting. Perioperative, functional, and oncologic outcomes of PA for multiple pheochromocytomas are shown. Results: Of 121 partial adrenalectomies performed, 10 procedures performed in eight patients for synchronous multiple ipsilateral pheochromocytomas were identified. All eight patients were symptomatic at presentation. The mean patient age was 30.6 years, median follow up was 12 months. The average surgical time was 228 minutes, average blood loss of 125mL, and average number of tumors removed was 2.6 per adrenal. In total, 26 tumors were removed, 24 were pathologically confirmed pheochromocytomas, while two were adrenal cortical hyperplasia. After surgery, all patients had resolution of their symptoms, one patient required steroid replacement postoperatively. On postoperative imaging, one patient had evidence of ipsilateral adrenal nodule at the prior resection site 2 months postoperatively, which was consistent with incomplete resection. Conclusions: Minimally invasive surgical resection of synchronous multiple pheochromocytomas is feasible with acceptable perioperative, functional, and short-term oncologic outcomes.
C1 [Gupta, Gopal N.; Benson, Jonas S.; Ross, Michael J.; Sundaram, Vani S.] Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA.
[Lin, Kelly Y.; Pinto, Peter A.; Linehan, W. Marston; Bratslavsky, Gennady] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Gupta, GN (reprint author), Loyola Univ, Med Ctr, Stritch Sch Med, Dept Urol, Maywood, IL 60153 USA.
EM gogupta@lumc.edu
FU National Institute of Health (NIH)
FX This research was funded by the National Institute of Health (NIH)
intramural research program.
NR 16
TC 2
Z9 3
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0892-7790
EI 1557-900X
J9 J ENDOUROL
JI J. Endourol.
PD JAN 1
PY 2014
VL 28
IS 1
BP 112
EP 116
DI 10.1089/end.2013.0298
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 284ZM
UT WOS:000329361400020
PM 23998199
ER
PT J
AU Glass, RI
Parashar, U
Patel, M
Gentsch, J
Jiang, BM
AF Glass, Roger I.
Parashar, Umesh
Patel, Manish
Gentsch, Jon
Jiang, Baoming
TI Rotavirus vaccines: Successes and challenges
SO JOURNAL OF INFECTION
LA English
DT Article
DE Rotavirus; Vaccines; Childhood diarrhea
ID CHILDHOOD DIARRHEA; UNITED-STATES; ACUTE GASTROENTERITIS; VACCINATION
PROGRAMS; GLOBAL SEASONALITY; YOUNG-CHILDREN; INFECTION; INFANTS;
EFFICACY; ANTIBODY
AB Since 2006, the availability of two new rotavirus vaccines has raised enthusiasm to consider the eventual control and elimination of severe rotavirus diarrhea through the global use of vaccines. Rotavirus remains the most severe cause of acute diarrhea in children worldwide responsible for several hundred thousands of deaths in low income countries and up to half of hospital admissions for diarrhea around the world. The new vaccines have been recommended by WHO for all infants and in more than 47 countries, their introduction into routine childhood immunization programs has led to a remarkable decline in hospital admissions and even deaths within 3 years of introduction. Challenges remain with issues of vaccine finance globally and the problem that these live oral vaccines perform less well in low income settings where they are needed most. Ongoing research that will accompany vaccine introduction might help address these issues of efficacy and new vaccines and novel financing schemes may both help make these vaccines universally available and affordable in the decade. Published by Elsevier Ltd on behalf of The British Infection Association.
C1 [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Parashar, Umesh; Patel, Manish; Gentsch, Jon; Jiang, Baoming] Ctr Dis Control & Prevent, Viral Gastroenteritis Team, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,Mailstop 2220, Bethesda, MD 20892 USA.
EM glassr@mail.nih.gov; uap2@CDC.GOV; aul3@CDC.GOV; jrg4@CDC.GOV;
bxj4@CDC.GOV
FU CDC; U.S. Government
FX All of this work has been funded through the CDC and the U.S.
Government.
NR 59
TC 28
Z9 30
U1 3
U2 10
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
EI 1532-2742
J9 J INFECTION
JI J. Infect.
PD JAN
PY 2014
VL 68
SU 1
BP S9
EP S18
DI 10.1016/j.jinf.2013.09.010
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 283CN
UT WOS:000329222500003
PM 24156947
ER
PT J
AU Hara, K
Rivera, MM
Koh, C
DeMino, M
Page, S
Nagabhyru, PR
Rehermann, B
Liang, TJ
Hoofnagle, JH
Heller, T
AF Hara, Koji
Rivera, Maria M.
Koh, Christopher
DeMino, Mary
Page, Sandra
Nagabhyru, Pothu Raju
Rehermann, Barbara
Liang, T. Jake
Hoofnagle, Jay H.
Heller, Theo
TI Sequence Analysis of Hepatitis C Virus From Patients With Relapse After
a Sustained Virological Response: Relapse or Reinfection?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Hepatitis C virus; late relapse; sequence; liver
ID TERM-FOLLOW-UP; INTERFERON; RIBAVIRIN; THERAPY; INFECTION
AB Background. A sustained virological response (SVR) is the major end point of therapy for chronic hepatitis C virus (ICV) infection. Late relapse of infection is rare and poorly characterized. Three of 103 patients with a SVR treated at the National Institutes of Health had late relapse. We evaluated fICV RNA sequences in serum and liver tissue to distinguish relapse from reinfection.
Methods. Per patient, 10-22 clones of amplified 5' untranslated region were evaluated in pretreatment and relapse serum specimens and in liver biopsy specimens obtained during SVR. Genotypes and sequence diversity were evaluated. Four patients whose infection relapsed before they reached a SVR (ie, the early relapse group) were used as a comparison.
Results. Results of tests for detection of serum IICV RNA in all patients with late relapse were repeatedly negative during the first 24 weeks after therapy but became positive 8, 75, and 78 months after SVR. Reinfection risk factors were absent in 2 of 3 patients. In all patients with early or late relapse, apart from minor variations, the original IICV sequence was present before treatment and after relapse. All liver biopsy specimens from patients with late relapse were IICV RNA positive at SVR, with sequences nearly identical to those of specimens obtained at other time points.
Conclusions. Sequence comparisons suggest that reappearance of fICV RNA years after a SVR can be from relapse of the initial viral infection rather than reinfection from a different virus.
C1 [Hara, Koji; Rivera, Maria M.; Koh, Christopher; DeMino, Mary; Page, Sandra; Nagabhyru, Pothu Raju; Rehermann, Barbara; Liang, T. Jake; Hoofnagle, Jay H.; Heller, Theo] NIDDK, Translat Hepatol Unit, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Heller, T (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Rm 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM theller@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 18
TC 18
Z9 18
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 1
PY 2014
VL 209
IS 1
BP 38
EP 45
DI 10.1093/infdis/jit541
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 282FY
UT WOS:000329157000008
PM 24127561
ER
PT J
AU Ng, OT
Laeyendecker, O
Redd, AD
Munshaw, S
Grabowski, MK
Paquet, AC
Evans, MC
Haddad, M
Huang, W
Robb, ML
Reynolds, SJ
Gray, RH
Wawer, MJ
Serwadda, D
Eshleman, SH
Quinn, TC
AF Ng, Oon Tek
Laeyendecker, Oliver
Redd, Andrew D.
Munshaw, Supriya
Grabowski, Mary K.
Paquet, Agnes C.
Evans, Mark C.
Haddad, Mojgan
Huang, Wei
Robb, Merlin L.
Reynolds, Steven J.
Gray, Ronald H.
Wawer, Maria J.
Serwadda, David
Eshleman, Susan H.
Quinn, Thomas C.
TI HIV Type 1 Polymerase Gene Polymorphisms Are Associated With Phenotypic
Differences in Replication Capacity and Disease Progression
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV-1 Subtype; subtype A; subtype D; disease progression; polymerase;
replication capacity; amino acid polymorphisms
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DECLINE; DRUG-SUSCEPTIBILITY;
CATALYTIC EFFICIENCY; VIRAL SUBTYPE; NAIVE ADULTS; INFECTION; UGANDA;
RAKAI; IMPACT
AB Background. Determinants of intersubtype differences in human immunodeficiency virus type 1 (HIV-1) clinical disease progression remain unknown.
Methods. HIV-1 subtype was independently determined for 5 separate genomic regions in 396 HIV-1 seroconverters from Rakai, Uganda, using a multiregion hybridization assay. Replication capacities (RC) in samples from a subset of 145 of these subjects were determined. HIV-1 genomic regions and poi RC were examined for association with disease progression. Amino acid polymorphisms were examined for association with pot RC.
Results. In multivariate analyses, the hazard for progression to the composite end point (defined as a CD4+ Tcell count <250 cells/mm(3), antiretroviral therapy initiation, or death) among patients with subtype D pot infection was 2.4 times the hazard for those infected with subtype A pol infection (P =.001). Compared with subtype A pol (the reference group), the hazard for progression to the composite end point for subtype D pol infection with a pol RC >67% (ie, the median pot RC) was significantly greater (HR, 4.6; 95% confidence interval [CI], 1.9-11.0; P =.001), whereas the hazard for progression to the composite end point for subtype D pol infection with a pol RC <= 67% was not significantly different (HR, 2.2; 959/0 CI, 1.0-4.9; P =.051). Amino acid substitutions at protease positions 62 and 64 and at reverse transcriptase position 272 were associated with significant differences in pot RC.
Conclusion. HIV-1 pol gene intersubtype and RC differences are associated with disease progression and may be influenced by amino acid polymorphisms.
C1 [Ng, Oon Tek; Laeyendecker, Oliver; Munshaw, Supriya; Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
[Eshleman, Susan H.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Grabowski, Mary K.; Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Laeyendecker, Oliver; Redd, Andrew D.; Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Robb, Merlin L.] US Mil HIV Res Program, Henry M Jackson Fdn, Rockville, MD USA.
[Paquet, Agnes C.; Evans, Mark C.; Haddad, Mojgan; Huang, Wei] Monogram Biosci, San Francisco, CA USA.
[Ng, Oon Tek] Tan Tock Seng Hosp, Dept Infect Dis, Singapore, Singapore.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, John Rangos Sr Bldg,Rm 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Singapore National Medical Research Training Fellowship Grant
[EDG10nov070]; National Institutes of Health (NIH) [NIDA R01 DA024565];
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, NIH
FX This work was supported by a Singapore National Medical Research
Training Fellowship Grant (EDG10nov070 to O. T. N.), the National
Institutes of Health (NIH; NIDA R01 DA024565 to S. M.), and the Division
of Intramural Research, National Institute of Allergy and Infectious
Diseases, NIH.
NR 25
TC 3
Z9 3
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JAN 1
PY 2014
VL 209
IS 1
BP 66
EP 73
DI 10.1093/infdis/jit425
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 282FY
UT WOS:000329157000011
PM 23922373
ER
PT J
AU Evangelou, IE
Oh, U
Massoud, R
Jacobson, S
AF Evangelou, Iordanis E.
Oh, Unsong
Massoud, Raya
Jacobson, Steven
TI HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis: Semiautomatic
Quantification of Spinal Cord Atrophy from 3-Dimensional MR Images
SO JOURNAL OF NEUROIMAGING
LA English
DT Article
DE Spinal cord; HTLV-I; HAM; TSP; MRI; atrophy
ID MAGNETIC-RESONANCE IMAGES; CLINICAL-FEATURES; HAM/TSP; INFECTION;
CARRIERS
AB BACKGROUNDHuman T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a disabling neurological disorder characterized by inflammatory changes in the spinal cord. We used a semiautomatic technique to quantify spinal cord volume from 3-dimensional MR images of patients with HAM/TSP.
METHODSFive patients and 5 matched healthy volunteers (HVs) underwent MRI of the cervical and thoracic spinal cord at 1.5 T. Quantification of the spinal cord volume was obtained from 3-dimensional MR images using a semiautomatic technique based on level sets. An unpaired t-test was used to assess statistical significance.
RESULTSSignificant differences were found between mean spinal cord volume of HVs and HAM/TSP patients. The thoracic spinal cord volume was 14,050 981 mm(3) for HVs and 8,774 +/- 2,218 mm(3) for HAM/TSP patients (P = .0079), a reduction of 38%. The cervical spinal cord volume was 9,721 +/- 797 mm(3) for HVs and 6,589 +/- 897 mm(3) for HAM/TSP patients (P = .0079), a reduction of 32%. These results suggest that atrophy is evident throughout the spinal cord not routinely quantified.
CONCLUSIONSSemiautomatic spinal cord volume quantification is a sensitive technique for quantifying the extent of spinal cord involvement in HAM/TSP.
C1 [Evangelou, Iordanis E.; Oh, Unsong; Massoud, Raya; Jacobson, Steven] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Evangelou, IE (reprint author), NINDS, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10-5C103, Bethesda, MD 20892 USA.
EM iordanis_evangelou@yahoo.com
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 12
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1051-2284
EI 1552-6569
J9 J NEUROIMAGING
JI J. Neuroimaging
PD JAN
PY 2014
VL 24
IS 1
BP 74
EP 78
DI 10.1111/j.1552-6569.2011.00648.x
PG 5
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 286ZZ
UT WOS:000329509100012
PM 22303896
ER
PT J
AU Corcoran, AE
Commons, KG
Wu, YM
Smith, JC
Harris, MB
Richerson, GB
AF Corcoran, Andrea E.
Commons, Kathryn G.
Wu, Yuanming
Smith, Jeffrey C.
Harris, Michael B.
Richerson, George B.
TI Dual Effects of 5-HT1a Receptor Activation on Breathing in Neonatal Mice
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE 8-OH-DPAT; Lmx1b; serotonin
ID CENTRAL SEROTONIN NEURONS; BROWN ADIPOSE-TISSUE; THERMOREGULATORY
CONTROL; RESPIRATORY RHYTHM; TRANSGENIC MICE; CONSCIOUS RATS; RAPHE
NEURONS; IN-VITRO; 8-OH-DPAT; AGONIST
AB Inhibitory 5-HT1a receptors are located on serotonin (5-HT) neurons (autoreceptors) as well as neurons of the respiratory network (heteroreceptors). Thus, effects on breathing of 5-HT1a agonists, such as (R)-(+)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), could either be due to decreased firing of 5-HT neurons or direct effects on the respiratory network. Mice in which the transcription factor LMX1B is genetically deleted selectively in Pet1-1-expressing cells (Lmx1b(f/f/p)) essentially have complete absence of central 5-HT neurons, providing a unique opportunity to separate the effect of activation of downstream 5-HT1a heteroreceptors from that of autoreceptors. We used rhythmically active medullary slices from wild-type (WT) and Lmx1b(f/f/p) neonatal mice to differentiate autoreceptor versus heteroreceptor effects of 8-OH-DPAT on hypoglossal nerve respiratory output. 8-OH-DPAT transiently increased respiratory burst frequency in Lmx1b(f/f/p) preparations, but not inWTslices. This excitation was abolished when synaptic inhibition was blocked by GABAergic/glycinergic receptor antagonists. Conversely, after 10 min of application, frequency in Lmx1b(f/f/p) slices was not different from baseline, whereas it was significantly depressed in WT slices. In WT mice in vivo, subcutaneous injection of 8-OH-DPAT produced similar biphasic respiratory effects as in Lmx1b(f/f/p) mice. We conclude that 5-HT1a receptor agonists have two competing effects: rapid stimulation of breathing due to excitation of the respiratory network, and delayed inhibition of breathing due to autoreceptor inhibition of 5-HT neurons. The former effect is presumably due to inhibition of inhibitory interneurons embedded in the respiratory network.
C1 [Corcoran, Andrea E.; Harris, Michael B.] Univ Alaska Fairbanks, Dept Biol & Wildlife, Fairbanks, AK 99775 USA.
[Corcoran, Andrea E.; Richerson, George B.] Yale Univ, Dept Neurol, New Haven, CT 06520 USA.
[Corcoran, Andrea E.; Richerson, George B.] Yale Univ, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA.
[Corcoran, Andrea E.] Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA.
[Commons, Kathryn G.] Boston Childrens Hosp, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA.
[Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Richerson, George B.] Vet Affairs Med Ctr, Iowa City, IA 52242 USA.
[Wu, Yuanming; Richerson, George B.] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
[Wu, Yuanming; Richerson, George B.] Univ Iowa, Dept Mol Physiol & Biophys, Iowa City, IA 52242 USA.
RP Corcoran, AE (reprint author), Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM andrea.e.corcoran@dartmouth.edu
RI Harris, Michael/A-3809-2010
FU Intramural Research Program of the NIH; NINDS; NIH [2U54NS041069];
NIH/NICHD [P01HD36379, R01HD052772]
FX This work was supported in part by the Intramural Research Program of
the NIH, NINDS, and from the NIH Grants 2U54NS041069, NIH/NICHD,
P01HD36379, and R01HD052772.
NR 52
TC 8
Z9 9
U1 0
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 1
PY 2014
VL 34
IS 1
BP 51
EP 59
DI 10.1523/JNEUROSCI.0864-13.2014
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 282NE
UT WOS:000329177800005
PM 24381267
ER
PT J
AU Cheng, Q
Yakel, JL
AF Cheng, Qing
Yakel, Jerrel L.
TI Presynaptic alpha 7 Nicotinic Acetylcholine Receptors Enhance
Hippocampal Mossy Fiber Glutamatergic Transmission via PKA Activation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; PROTEIN-KINASE-A; EXCITATORY
SYNAPTIC-TRANSMISSION; PREFRONTAL CORTEX; NERVE-TERMINALS; RAT
HIPPOCAMPUS; COGNITIVE PERFORMANCE; ALLOSTERIC MODULATOR; TRANSMITTER
RELEASE; KAINATE RECEPTORS
AB Nicotinic acetylcholine receptors (nAChRs) are expressed widely in the CNS, and mediate both synaptic and perisynaptic activities of endogenous cholinergic inputs and pharmacological actions of exogenous compounds (e.g., nicotine and choline). Behavioral studies indicate that nicotine improves such cognitive functions as learning and memory. However, the mechanism of nicotine's action on cognitive function remains elusive. We performed patch-clamp recordings from hippocampal CA3 pyramidal neurons to determine the effect of nicotine on mossy fiber glutamatergic synaptic transmission. We found that nicotine in combination with NS1738, an alpha 7 nAChR-positive allosteric modulator, strongly potentiated the amplitude of evoked EPSCs (eEPSCs), and reduced the EPSC paired-pulse ratio. The action of nicotine and NS1738 was mimicked by PNU-282987 (an alpha 7 nAChR agonist), and was absent in alpha 7 nAChR knock-out mice. These data indicate that activation of alpha 7 nAChRs was both necessary and sufficient to enhance the amplitude of eEPSCs. BAPTA applied postsynaptically failed to block the action of nicotine and NS1738, suggesting again a presynaptic action of the alpha 7 nAChRs. We also observed alpha 7 nAChR-mediated calcium rises at mossy fiber giant terminals, indicating the presence of functional alpha 7 nAChRs at presynaptic terminals. Furthermore, the addition of PNU-282987 enhanced action potential-dependent calcium transient at these terminals. Last, the potentiating effect of PNU-282987 on eEPSCs was abolished by inhibition of protein kinase A (PKA). Our findings indicate that activation of alpha 7 nAChRs at presynaptic sites, via a mechanism involving PKA, plays a critical role in enhancing synaptic efficiency of hippocampal mossy fiber transmission.
C1 [Cheng, Qing; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, 111 TW Alexander Dr, Durham, NC 27709 USA.
EM yakel@niehs.nih.gov
FU National Institute of Environmental Health Sciences Intramural Research
Program/National Institutes of Health
FX This research was funded by the National Institute of Environmental
Health Sciences Intramural Research Program/National Institutes of
Health. We thank Pattie Lamb for genotyping and mouse colony management,
and Jeff Tucker for technical support of confocal microscopy. We
appreciate Drs. Georgia Alexander, Serena Dudek, and Christian Erxleben
for the helpful reading and suggestions on this manuscript.
NR 85
TC 19
Z9 20
U1 1
U2 12
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JAN 1
PY 2014
VL 34
IS 1
BP 124
EP 133
DI 10.1523/JNEUROSCI.2973-13.2014
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 282NE
UT WOS:000329177800011
PM 24381273
ER
PT J
AU Nduom, EK
Zhuang, ZP
Lonser, RR
AF Nduom, Edjah K.
Zhuang, Zhengping
Lonser, Russell R.
TI Blood-brain barrier RESPONSE
SO JOURNAL OF NEUROSURGERY
LA English
DT Letter
C1 [Nduom, Edjah K.] Emory Univ, Atlanta, GA 30322 USA.
[Nduom, Edjah K.; Zhuang, Zhengping; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Lonser, Russell R.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA.
RP Nduom, EK (reprint author), Emory Univ, Atlanta, GA 30322 USA.
FU Intramural NIH HHS [Z99 NS999999]
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD JAN
PY 2014
VL 120
IS 1
BP 291
EP 291
PG 1
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 281GL
UT WOS:000329087900050
PM 24520575
ER
PT J
AU Shrestha, SS
Liow, JS
Lu, SY
Jenko, K
Gladding, RL
Svenningsson, P
Morse, CL
Zoghbi, SS
Pike, VW
Innis, RB
AF Shrestha, Stal Saurav
Liow, Jeih-San
Lu, Shuiyu
Jenko, Kimberly
Gladding, Robert L.
Svenningsson, Per
Morse, Cheryl L.
Zoghbi, Sami S.
Pike, Victor W.
Innis, Robert B.
TI C-11-CUMI-101, a PET Radioligand, Behaves as a Serotonin 1A Receptor
Antagonist and Also Binds to alpha(1) Adrenoceptors in Brain
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE CUMI-101; 5-HT1A receptor; alpha(1) adrenoceptor; cross-reactivity;
positron emission tomography (PET); S-35-GTP gamma S; homogenate binding
ID IN-VIVO; 5-HT1A RECEPTORS; AGONIST; RADIOTRACER; ALPHA(1)-ADRENOCEPTOR;
QUANTIFICATION; CONFOUNDS; AFFINITY; MONKEY
AB The PET radioligand C-11-CUMI-101 was previously suggested as a putative agonist radioligand for the serotonin 1A (5-hydroxytryptamine 1A [5-HT1A]) receptor in recombinant cells expressing human 5-HT1A receptor. However, a recent study showed that CUMI-101 behaved as a potent 5-HT(1)A receptor antagonist in rat brain. CUMI-101 also has moderate affinity (Ki = 6.75 nM) for alpha(1) adrenoceptors measured in vitro. The current study examined the functional properties and selectivity of CUMI-101, both in vitro and in vivo. Methods: The functional assay was performed using S-35-GTP gamma S (GTP is guanosine triphosphate) in primate brains. The cross-reactivity of CUMI-101 with alpha(1) adrenoceptors was performed using in vitro radioligand binding studies in rat, monkey, and human brains as well as in vivo PET imaging in mouse, rat, and monkey brains. Results: CUMI-101 did not stimulate S-35-GTP gamma S binding in primate brain, in contrast to 8-OH-DPAT, a potent 5-HT1A receptor agonist. Instead, CUMI-101 behaved as a potent 5-HT1A receptor antagonist by dose-dependently inhibiting 8-OH-DPAT-stimulated S-35-GTP gamma S binding. Both in vitro and in vivo studies showed that CUMI-101 had significant a1 adrenoceptor cross-reactivity. On average, across all 3 species examined, cross-reactivity was highest in the thalamus (>45%) and lowest in the neocortex and cerebellum (<10%). PET imaging further confirmed that only preblocking with WAY-100635 plus prazosin decreased C-11-CUMI-101 brain uptake to that of self-block. Conclusion: CUMI-101 behaves as a 5-HT1A receptor antagonist in primate brain, with significant, regional-dependent alpha(1) adrenoceptor cross-reactivity, limiting its potential use as a PET radioligand in humans.
C1 [Shrestha, Stal Saurav; Liow, Jeih-San; Lu, Shuiyu; Jenko, Kimberly; Gladding, Robert L.; Morse, Cheryl L.; Zoghbi, Sami S.; Pike, Victor W.; Innis, Robert B.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Shrestha, Stal Saurav; Svenningsson, Per] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
RP Shrestha, SS (reprint author), NIH, 10 Ctr Dr B1D43, Bethesda, MD 20892 USA.
EM saurav.shrestha@nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX We gratefully acknowledge the support of the Intramural Research Program
of the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH). PMOD Technologies (Zurich, Switzerland)
graciously provided image analysis and modeling software. We thank Dr.
Ramin Parsey and Dr. Victoria Arango for providing human brain tissues,
Ioline Henter for excellent editorial assistance, Kacey Anderson for
assisting with PET imaging, and the joint National Institutes of
Health-Karolinska Institutet Doctoral Program in Neuroscience.
NR 24
TC 6
Z9 7
U1 0
U2 4
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD JAN 1
PY 2014
VL 55
IS 1
BP 141
EP 146
DI 10.2967/jnumed.113.125831
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 282PG
UT WOS:000329183600029
PM 24385311
ER
PT J
AU Guo, JX
Guo, N
Lang, LX
Kiesewetter, DO
Xie, QG
Li, QZ
Eden, HS
Niu, G
Chen, XY
AF Guo, Jinxia
Guo, Ning
Lang, Lixin
Kiesewetter, Dale O.
Xie, Qingguo
Li, Quanzheng
Eden, Henry S.
Niu, Gang
Chen, Xiaoyuan
TI F-18-Alfatide II and F-18-FDG Dual-Tracer Dynamic PET for Parametric,
Early Prediction of Tumor Response to Therapy
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE dual-tracer dynamic PET; parametric imaging; F-18-alfatide II; F-18-FDG;
therapy response
ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; INPUT FUNCTIONS; FDG-PET;
CHEMOTHERAPY; FEASIBILITY; MICROPET; HYPOXIA; CANCER
AB A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with F-18-alfatide II (F-18-AlF-NOTA-E[PEG(4)-c(RGDfk)](2)) and F-18-FDG for parametric monitoring of tumor responses to therapy. Methods: We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with F-18-alfatide II, followed 40 min later by F-18-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of F-18-alfatide II for the 40 min before F-18-FDG injection and then extrapolated to 90 min. The F-18-FDG tumor time-activity curve was isolated from the 90min dual-tracer tumor time-activity curve by subtracting the fitted F-18-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the F-18-alfatide II binding potential (Bp = k(3)/k(4)) and volume of distribution (VD) and F-18-FDG influx rate ((K-1 x k(3))/(k(2) + k(3))) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response. Results: The transport and binding rate parameters K-1-k(3) of F-18-alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and VD correlated well with the parameters from the 60-min single-tracer scan (R-2 > 0.95). Compared with the results of single-tracer PET imaging, F-18-FDG tumor uptake and influx were recovered well from dualtracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of F-18-alfatide II or F-18-FDG were observed, both F-18-alfatide II Bp and F-18-FDG influx from kinetic analysis in tumors showed significant decreases. For therapy of MDA-MB-435 tumors with paclitaxel protein-bound particles, a significant decrease was observed only with F-18-alfatide II Bp value from kinetic analysis but not F-18-FDG influx. Conclusion: The parameters fitted with compartmental modeling from the dual-tracer dynamic imaging are consistent with those from single-tracer imaging, substantiating the feasibility of this methodology. Even though no significant differences in tumor size were found until 5 d after doxorubicin treatment started, at day 3 there were already substantial differences in F-18-alfatide II Bp and F-18-FDG influx rate. Dual-tracer imaging can measure F-18-alfatide II Bp value and F-18-FDG influx simultaneously to evaluate tumor angiogenesis and metabolism. Such changes are known to precede anatomic changes, and thus parametric imaging may offer the promise of early prediction of therapy response.
C1 [Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Hubei, Peoples R China.
[Guo, Jinxia; Xie, Qingguo] Huazhong Univ Sci & Technol, Wuhan Natl Lab Optoelect, Wuhan 430074, Hubei, Peoples R China.
[Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, Natl Inst Hlth NIBIB, Bethesda, MD USA.
[Guo, Jinxia; Guo, Ning] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen, Peoples R China.
[Li, Quanzheng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA.
[Eden, Henry S.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, Natl Inst Hlth NIBIB, Bethesda, MD USA.
RP Chen, XY (reprint author), NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; shawn.chen@nih.gov
FU National Key Basic Research Program (973 Project) [2013CB733802];
Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)
FX The costs of publication of this article were defrayed in part by the
payment of page charges. Therefore, and solely to indicate this fact,
this article is hereby marked "advertisement" in accordance with 18 USC
section 1734. This work was supported in part by National Key Basic
Research Program (973 Project; 2013CB733802) and by the Intramural
Research Program of the National Institute of Biomedical Imaging and
Bioengineering (NIBIB), National Institutes of Health (NIH). No other
potential conflict of interest relevant to this article was reported.
NR 36
TC 12
Z9 13
U1 2
U2 19
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD JAN 1
PY 2014
VL 55
IS 1
BP 154
EP 160
DI 10.2967/jnumed.113.122069
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 282PG
UT WOS:000329183600031
PM 24232871
ER
PT J
AU Shechner, T
Rimon-Chakir, A
Britton, JC
Lotan, D
Apter, A
Bliese, PD
Pine, DS
Bar-Haim, Y
AF Shechner, Tomer
Rimon-Chakir, Adi
Britton, Jennifer C.
Lotan, Danny
Apter, Alan
Bliese, Paul D.
Pine, Daniel S.
Bar-Haim, Yair
TI Attention Bias Modification Treatment Augmenting Effects on Cognitive
Behavioral Therapy in Children With Anxiety: Randomized Controlled Trial
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE anxiety; attention bias; attention bias modification treatment (ABMT);
cognitive behavioral therapy (CBT)
ID EMOTIONAL DISORDERS; PEDIATRIC ANXIETY; ANXIOUS CHILDREN;
CLINICAL-TRIAL; FOLLOW-UP; YOUTH; AUGMENTATION; INDIVIDUALS
AB Objective: Attention bias modification treatment (ABMT) is a promising novel treatment for anxiety disorders, but clinical trials have focused largely on stand-alone formats among adults. This randomized controlled trial examined the augmenting effects of threat-based ABMT on cognitive behavioral therapy (CBT) in clinically anxious youth. Method: Sixty-three treatment-seeking children with anxiety disorder were randomly assigned to 1 of the following 3 treatment groups: ABMT + CBT; ABMT placebo + CBT; and CBT-alone. Participants in the 2 ABMT conditions received repeated training on dot-probe tasks either designed to shift attention away from threats (active) or designed to induce no changes in attention patterns (placebo). Primary outcome measures were frequency and severity of anxiety symptoms as determined by a clinician using a semi-structured interview. Self- and parent-rated anxiety measures and threat-related attention bias scores were also measured before and after treatment. Results: Both the active and placebo ABMT groups showed greater reductions in clinician-rated anxiety symptoms than the CBT-alone group. Furthermore, only the active ABMT group showed significant reduction in self- or parent-rated anxiety symptoms. Finally, all groups showed a shift in attention patterns across the study, starting with a bias toward threat at baseline and shifting attention away from threat after treatment. Conclusions: Active and placebo ABMT might augment the clinical response to CBT for anxiety. This effect could arise from benefits associated with performing computer-based paradigms such as the dot-probe task. Given the absence of group differences in attention-bias changes during treatment, possible mechanisms and methodological issues underlying the observed findings are discussed. Clinical trial registration information Augmenting Effects of ABMT on CBT in Anxious Children: A Randomized Clinical Trial; http://clinicaltrials.gov/; NCT01730625.
C1 [Shechner, Tomer] Univ Haifa, IL-3498838 Haifa, Israel.
[Rimon-Chakir, Adi; Bar-Haim, Yair] Tel Aviv Univ, IL-69978 Tel Aviv, Israel.
[Britton, Jennifer C.] Univ Miami, Coral Gables, FL 33124 USA.
[Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
RP Shechner, T (reprint author), Univ Haifa, Psychol Dept, IL-3498838 Haifa, Israel.
FU Adler Center for Research in Child Development and Psychopathology;
National Institutes of Health
FX This study was partially supported by a grant from the Adler Center for
Research in Child Development and Psychopathology to Dr. Bar-Haim and by
the National Institutes of Health intramural research program.
NR 29
TC 35
Z9 36
U1 1
U2 24
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JAN
PY 2014
VL 53
IS 1
BP 61
EP 71
DI 10.1016/j.jaac.2013.09.016
PG 11
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 280GG
UT WOS:000329016100008
PM 24342386
ER
PT J
AU Scahill, L
Dimitropoulos, A
McDougle, CJ
Aman, MG
Feurer, ID
McCracken, JT
Tierney, E
Pu, J
White, S
Lecavalier, L
Hallett, V
Bearss, K
King, B
Arnold, LE
Vitiello, B
AF Scahill, Lawrence
Dimitropoulos, Anastasia
McDougle, Christopher J.
Aman, Michael G.
Feurer, Irene D.
McCracken, James T.
Tierney, Elaine
Pu, Jie
White, Susan
Lecavalier, Luc
Hallett, Victoria
Bearss, Karen
King, Bryan
Arnold, L. Eugene
Vitiello, Benedetto
TI Children's Yale-Brown Obsessive Compulsive Scale in Autism Spectrum
Disorder: Component Structure and Correlates of Symptom Checklist
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE autism spectrum disorder; clinical trials; outcome measures; repetitive
behavior
ID PERVASIVE DEVELOPMENTAL DISORDERS; SERIOUS BEHAVIORAL-PROBLEMS;
REPETITIVE BEHAVIOR; RISPERIDONE; QUESTIONNAIRE; RELIABILITY;
VALIDATION; INTERVIEW; TRIAL; SELF
AB Objective: Repetitive behaviors in autism spectrum disorders (ASD) range from motor stereotypy to immersion in restricted interests. The modified Children's Yale Brown Obsessive Compulsive Scale for children with autism spectrum disorder (CYBOCS-ASD) includes a Symptom Checklist (behavior present or absent) and 5 severity scales (Time Spent, Interference, Distress, Resistance and Control). Method: We assembled CYBOCS-ASD data from 3 Research Units on Pediatric Psychopharmacology Autism Network trials to explore the component structure of repetitive behaviors in children with ASD. Raters trained to reliability conducted the CYBOCS-ASD in 272 medication-free subjects. Fifteen Symptom Checklist items were endorsed for less than 5% of the sample and were dropped. Principal component analysis was used to explore the clustering of 23 checklist items. Component scores computed for each subject were correlated with other measures. We also examined the distribution of severity scales. Results: The subjects (229 boys and 43 girls; mean age = 7.8 +/- 2.6 years) met criteria for an ASD; half were intellectually disabled. The PCA resulted in a 5-component solution to classify repetitive behaviors (34.4% of the variance): hoarding and ritualistic behavior; sensory and arranging behavior; sameness and self-injurious behavior; stereotypy; restricted interests. Sensory and arranging and stereotypy components were associated with lower adaptive functioning (Pearson r = 0.2-0.3; p < .003). The resistance scale showed little variation, with more than 60% of the sample with the highest score. Conclusions: Rarely endorsed items can be dropped from the Checklist. The resistance item does not appear to be relevant for children with ASD.
C1 [Scahill, Lawrence; Bearss, Karen] Emory Univ, Atlanta, GA 30322 USA.
[Dimitropoulos, Anastasia] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[McDougle, Christopher J.] Harvard Univ, Cambridge, MA 02138 USA.
[Aman, Michael G.; Lecavalier, Luc; Arnold, L. Eugene] Ohio State Univ, Columbus, OH 43210 USA.
[Feurer, Irene D.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[McCracken, James T.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Tierney, Elaine] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Pu, Jie] Univ Arizona, Tucson, AZ 85721 USA.
[White, Susan] Virginia Polytech Univ, Blacksburg, VA 24061 USA.
[Hallett, Victoria] Kings Coll London, London WC2R 2LS, England.
[King, Bryan] Univ Washington, Seattle, WA 98195 USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD USA.
RP Scahill, L (reprint author), Marcus Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
EM lawrence.scahill@emory.edu
OI Scahill, Lawrence/0000-0001-5073-1707
FU NIMH by Research Unit on Pediatric Psychopharmacology (RUPP), Yale
[U10MH66764]; NIMH by Research Unit on Pediatric Psychopharmacology
(RUPP), Indiana University [U10MH66766]; NIMH by Research Unit on
Pediatric Psychopharmacology (RUPP), Ohio, State University
[U10MH66768]; Yale CTSA from the National Center for Research Resources
(NCRR) [UL1 RR024139]; IU CTSA from the National Center for Research
Resources (NCRR) [UL1 RR025761]; OSU CTSA from the National Center for
Research Resources (NCRR) [UL1 RR025755]
FX This work was funded by NIMH by the following Research Units on
Pediatric Psychopharmacology (RUPP) grants: Yale, U10MH66764; Indiana
University, U10MH66766, and Ohio, State University, U10MH66768. This
publication was also supported by the Yale CTSA, UL1 RR024139, IU CTSA
UL1 RR025761, OSU CTSA UL1 RR025755 from the National Center for
Research Resources (NCRR).
NR 35
TC 6
Z9 7
U1 2
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JAN
PY 2014
VL 53
IS 1
BP 97
EP 107
DI 10.1016/j.jaac.2013.09.018
PG 11
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 280GG
UT WOS:000329016100011
PM 24342389
ER
PT J
AU Karlsson, EM
Pearson, LM
Kuzma, KM
Burkholder, TH
AF Karlsson, Eleanor M.
Pearson, Laura M.
Kuzma, Kristen M.
Burkholder, Tanya H.
TI Combined Evaluation of Commonly Used Techniques, Including PCR, for
Diagnosis of Mouse Fur Mites
SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
LA English
DT Article
ID MYOBIA-MUSCULI; MYOCOPTES-MUSCULINUS; MURINE ACARIASIS; INFECTIOUS
AGENTS; PARASITIC ECOLOGY; RODENT MITE; MICE; INFESTATION; MOXIDECTIN;
IVERMECTIN
AB Our study evaluated and compared the false-negative rates (FNR) of a wide array of fur-mite diagnostic tests, including 2 postmortem tests (pelt exam and sticky paper) and 3 antemortem tests (adhesive tape, fur pluck, and PCR). Past publications examining fur-mite diagnostic techniques primarily used paired comparisons, evaluating tests by their level of agreement with only one other test. However, different combinations or pairs of diagnostics are used in the different studies, making the results of these comparisons difficult to interpret across all available diagnostics. In the current study, mice from a conventionally maintained colony endemic for Myobia musculi were identified as positive based on at least one positive diagnostic test. From this pool of positive animals, the FNR of all tests were quantified. The PCR assay and the pelt exam performed the best, with 0% and 2% FNR respectively, whereas tape, fur-pluck, and sticky-paper tests showed 24%, 26%, and 36% FNR, respectively. Our study shows that for mice in a colony naturally infested with Myobia musculi, PCR testing can be used for reliable antemortem detection, and pelt exam performed by experienced examiners is reliable for postmortem detection.
C1 [Karlsson, Eleanor M.; Pearson, Laura M.; Kuzma, Kristen M.; Burkholder, Tanya H.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
RP Karlsson, EM (reprint author), NIH, Div Vet Resources, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA.
EM ellie.m.karlsson@gmail.com
FU Division of Veterinary Resources; Office of Research Services; NIH
FX This study was supported by the Division of Veterinary Resources, Office
of Research Services, and NIH.
NR 38
TC 1
Z9 1
U1 2
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1559-6109
J9 J AM ASSOC LAB ANIM
JI J. Amer. Assoc. Lab. Anim. Sci.
PD JAN
PY 2014
VL 53
IS 1
BP 69
EP 73
PG 5
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 283UO
UT WOS:000329272700010
PM 24411782
ER
PT J
AU Shaikh, Q
Kamal, AK
AF Shaikh, Quratulain
Kamal, Ayeesha Kamran
TI Can prophylactic antibiotics for aspiration improve stroke outcomes? The
PANTHERIS trial
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Fogarty Int Ctr, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Program, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43 TW008660]
NR 1
TC 0
Z9 0
U1 0
U2 1
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 2014
VL 64
IS 1
BP 98
EP 98
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 283OZ
UT WOS:000329257900027
PM 24605726
ER
PT J
AU Liu, SW
Wyatt, LS
Orandle, MS
Minai, M
Moss, B
AF Liu, Shin-Wu
Wyatt, Linda S.
Orandle, Marlene S.
Minai, Mahnaz
Moss, Bernard
TI The D10 Decapping Enzyme of Vaccinia Virus Contributes to Decay of
Cellular and Viral mRNAs and to Virulence in Mice
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HOST SHUTOFF PROTEIN; GENE-EXPRESSION; MICROARRAY ANALYSIS; DENDRITIC
CELLS; WILD-TYPE; IN-VIVO; INFECTION; REVEALS; REPLICATION; DEGRADATION
AB Posttranscriptional mechanisms are important for regulation of cellular and viral gene expression. The presence of the 5' cap structure m(7)G(5') ppp(5') Nm is a general feature of mRNAs that provides protection from exoribonuclease digestion and enhances translation. Vaccinia virus and other poxviruses encode enzymes for both cap synthesis and decapping. Decapping is mediated by two related enzymes, D9 and D10, which are synthesized before and after viral DNA replication, respectively. The timing of D10 synthesis correlates better with the shutdown of host gene expression, and deletion of this gene has been shown to cause persistence of host and viral mRNAs in infected cells. Here, we constructed specific mutant viruses in which translation of D10 was prevented by stop codons or activity of D10 was abrogated by catalytic site mutations, without other genomic alterations. Both mutants formed plaques of normal size and replicated to similar extents as the parental virus in monkey epithelial cells and mouse embryonic fibroblasts. The synthesis of viral proteins was slightly delayed, and cellular and viral mRNAs persisted longer in cells infected with the mutants compared to either the parental virus or clonal revertant. Despite the mild effects in vitro, both mutants were more attenuated than the revertants in intranasal and intraperitoneal mouse models, and less infectious virus was recovered from organs. In addition, there was less lung histopathology following intranasal infection with mutant viruses. These data suggest that the D10 decapping enzyme may help restrict antiviral responses by accelerating host mRNA degradation during poxvirus infection.
C1 [Liu, Shin-Wu; Wyatt, Linda S.; Moss, Bernard] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Orandle, Marlene S.; Minai, Mahnaz] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Rockville, MD USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, NIAID, NIH
FX The research was supported by the Division of Intramural Research,
NIAID, NIH.
NR 55
TC 12
Z9 12
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 2014
VL 88
IS 1
BP 202
EP 211
DI 10.1128/JVI.02426-13
PG 10
WC Virology
SC Virology
GA 282SW
UT WOS:000329194600018
PM 24155373
ER
PT J
AU Fenizia, C
Fiocchi, M
Jones, K
Parks, RW
Ceribelli, M
Chevalier, SA
Edwards, D
Ruscetti, F
Pise-Masison, CA
Franchini, G
AF Fenizia, Claudio
Fiocchi, Martina
Jones, Kathryn
Parks, Robyn Washington
Ceribelli, Michele
Chevalier, Sebastien A.
Edwards, Dustin
Ruscetti, Francis
Pise-Masison, Cynthia A.
Franchini, Genoveffa
TI Human T-Cell Leukemia/Lymphoma Virus Type 1 p30, but Not p12/p8,
Counteracts Toll-Like Receptor 3 (TLR3) and TLR4 Signaling in Human
Monocytes and Dendritic Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TROPICAL SPASTIC PARAPARESIS; INTERFERON REGULATORY FACTOR-3;
LEUKEMIA-VIRUS; HTLV-I; GENE-EXPRESSION; HUMAN MACROPHAGES; ALPHA/BETA
INTERFERON; INFECTION; ACTIVATION; PROTEIN
AB The human T-cell leukemia/lymphoma virus type 1 (HTLV-1) p30 protein, essential for virus infectivity in vivo, is required for efficient infection of human dendritic cells (DCs) but not B and T cells in vitro. We used a human monocytic cell line, THP-1, and dendritic cells to study the mechanism of p30 and p12/p8 requirements in these cell types. p30 inhibited the expression of interferon (IFN)-responsive genes (ISG) following stimulation by lipopolysaccharide (LPS) of Toll-like receptor 4 (TLR4) and by poly(I.C) of TLR3 but not of TLR7/8 with imiquimod. Results with THP-1 mirrored those for ex vivo human primary monocytes and monocyte-derived dendritic cells (Mo-mDC). The effect of p30 on TLR signaling was also demonstrated by ablating its expression within a molecular clone of HTLV-1. HTLV-1 infection of monocytes inhibited TLR3- and TLR4-induced ISG expression by 50 to 90% depending on the genes, whereas the isogenic clone p30 knockout virus was less effective at inhibiting TLR3 and TRL4 signaling and displayed lower infectivity. Viral expression and inhibition of ISG transcription was, however, rescued by restoration of p30 expression. A chromatin immunoprecipitation assay demonstrated that p30 inhibits initiation and elongation of PU.1-dependent transcription of IFN-alpha 1, IFN-beta, and TLR4 genes upon TLR stimulation. In contrast, experiments conducted with p12/p8 did not demonstrate an effect on ISG expression. These results provide a mechanistic explanation of the requirement of p30 for HTLV-1 infectivity in vivo, suggest that dampening interferon responses in monocytes and DCs is specific for p30, and represent an essential early step for permissive HTLV-1 infection and persistence.
C1 [Fenizia, Claudio; Parks, Robyn Washington; Edwards, Dustin; Pise-Masison, Cynthia A.; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA.
[Fiocchi, Martina] UNIMI, LITA Vialba, Immunol Lab, Milan, Italy.
[Jones, Kathryn] NCI, Basic Res Program, SAIC Frederick Inc, NIH, Frederick, MD 21701 USA.
[Chevalier, Sebastien A.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ruscetti, Francis] NCI, Expt Immunol Lab, CCR, Frederick, MD 21701 USA.
[Ceribelli, Michele] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
NR 55
TC 6
Z9 6
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 2014
VL 88
IS 1
BP 393
EP 402
DI 10.1128/JVI.01788-13
PG 10
WC Virology
SC Virology
GA 282SW
UT WOS:000329194600035
PM 24155397
ER
PT J
AU Koganti, S
de la Paz, A
Freeman, AF
Bhaduri-McIntosh, S
AF Koganti, Siva
de la Paz, Amanda
Freeman, Alexandra F.
Bhaduri-McIntosh, Sumita
TI B Lymphocytes from Patients with a Hypomorphic Mutation in STAT3 Resist
Epstein-Barr Virus-Driven Cell Proliferation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HYPER-IGE SYNDROME; ELEMENT-BINDING PROTEIN; SIGNAL TRANSDUCER;
GENE-EXPRESSION; VIRAL GENOME; EARLY EVENTS; TRANSCRIPTION; ACTIVATION;
INFECTION; DIFFERENTIATION
AB Epstein-Barr virus (EBV) oncogenes exert potent B cell proliferative effects. EBV infection gives rise to B cell lines that readily proliferate in culture. This ability of EBV represents a powerful tool to study cell proliferation. In efforts to delineate the contribution of signal transducer and activator of transcription 3 (STAT3) toward EBV-driven cell proliferation, we have discovered that B cells from patients with autosomal dominant hyper-IgE syndrome (AD-HIES) resist such EBV oncogene-driven outgrowth of cells. Patients with AD-HIES have a dominant negative mutation in their STAT3 gene which renders most of the protein nonfunctional. Exposure of healthy subject-derived B cells to EBV resulted in early activation of STAT3, rapidly followed by increased expression of its mRNA and protein. STAT3 upregulation preceded the expression of EBNA2, temporally one of the first viral oncogenes to be expressed. We found that STAT3 was necessary for subsequent survival and for proliferation of EBV-infected cells past the S phase of the cell cycle. Consequently, B cells from AD-HIES patients were prone to dying and accumulated in the S phase, thereby accounting for impaired cell outgrowth. Of importance, we have now identified a cohort of patients with a primary immunodeficiency disorder whose B cells oppose EBV-driven proliferative signals. These findings simultaneously reveal how EBV manipulates host STAT3 even before expression of viral oncogenes to facilitate cell survival and proliferation, processes fundamental to EBV lymphomagenesis.
C1 [Koganti, Siva; Bhaduri-McIntosh, Sumita] SUNY Stony Brook, Sch Med, Dept Pediat, Stony Brook, NY 11794 USA.
[Koganti, Siva; Bhaduri-McIntosh, Sumita] SUNY Stony Brook, Sch Med, Stony Brook Childrens Hosp, Stony Brook, NY 11794 USA.
[de la Paz, Amanda] Thomas Jefferson Univ, Dept Family & Community Med, Philadelphia, PA 19107 USA.
[Freeman, Alexandra F.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bhaduri-McIntosh, Sumita] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
RP Bhaduri-McIntosh, S (reprint author), SUNY Stony Brook, Sch Med, Dept Pediat, Stony Brook, NY 11794 USA.
EM sumita.bhaduri-mcintosh@stonybrookmedicine.edu
FU The Research Foundation for The State University of New York; [K08
AI062732]; [K12 HD001401]; [1UL1RR024139-02]
FX This study was supported by K08 AI062732, K12 HD001401, 1UL1RR024139-02,
and funds from The Research Foundation for The State University of New
York to S. B.-M.
NR 47
TC 8
Z9 9
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 2014
VL 88
IS 1
BP 516
EP 524
DI 10.1128/JVI.02601-13
PG 9
WC Virology
SC Virology
GA 282SW
UT WOS:000329194600047
PM 24173212
ER
PT J
AU Nguyen, HT
Shukla, P
Torian, U
Faulk, K
Emerson, SU
AF Nguyen, H. T.
Shukla, P.
Torian, U.
Faulk, K.
Emerson, S. U.
TI Hepatitis E Virus Genotype 1 Infection of Swine Kidney Cells In Vitro Is
Inhibited at Multiple Levels
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RECEPTOR-BINDING; CULTURE-SYSTEM; ORF3 PROTEIN; REPLICATION;
RECOMBINANT; DISCOVERY; PRIMATES; HEPATOMA; RELEASE; DEPENDS
AB Genotype 1 hepatitis E viruses (HEVs) are restricted to primate hosts, whereas genotype 3 HEVs predominantly infect swine, in addition to primates. In order to identify possible determinants of the host range, infectious recombinant viruses and chimeras of a genotype 1 isolate and a genotype 3 isolate were compared for their ability to infect versus transfect cultured human HepG2/C3A cells and swine LLC-PK cells. The patterns of luciferase expression from virus replicons containing the Gaussia luciferase gene in place of the viral ORF2 or ORF3 genes demonstrated that translation of the ORF2 capsid gene of genotype 1 virus is severely inhibited in swine kidney cells compared to its translation in rhesus macaque kidney or human liver cells. Therefore, this virus may produce insufficient capsid protein for optimal assembly in swine cells. Infectivity assays with a virus containing a chimeric capsid protein confirmed that amino acids 456 to 605 of the virus capsid protein comprised the virus receptor-binding region and suggested that genotype 1 viruses may be prevented from infecting swine because genotype 1 viruses are unable to enter swine cells. Rhesus macaque cells appeared to be better than human cells for growing the genotype 1 virus. These cell and virus combinations may serve as a useful in vitro model with which to study determinants of the natural host range of this virus.
C1 [Nguyen, H. T.; Shukla, P.; Torian, U.; Emerson, S. U.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Faulk, K.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM semerson@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 30
TC 10
Z9 10
U1 0
U2 1
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 2014
VL 88
IS 2
BP 868
EP 877
DI 10.1128/JVI.02205-13
PG 10
WC Virology
SC Virology
GA 282SY
UT WOS:000329194900011
PM 24198420
ER
PT J
AU Chen, WZ
Feng, Y
Prabakaran, P
Ying, TL
Wang, YP
Sun, JP
Macedo, CDS
Zhu, ZY
He, YX
Polonis, VR
Dimitrov, DS
AF Chen, Weizao
Feng, Yang
Prabakaran, Ponraj
Ying, Tianlei
Wang, Yanping
Sun, Jianping
Macedo, Camila D. S.
Zhu, Zhongyu
He, Yuxian
Polonis, Victoria R.
Dimitrov, Dimiter S.
TI Exceptionally Potent and Broadly Cross-Reactive, Bispecific Multivalent
HIV-1 Inhibitors Based on Single Human CD4 and Antibody Domains
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; IMMUNODEFICIENCY-VIRUS TYPE-1; GP120
ENVELOPE GLYCOPROTEIN; AIDS-RELATED COMPLEX; HUMAN SOLUBLE CD4;
CRYSTAL-STRUCTURE; T-CELLS; PHASE-I; NEUTRALIZING ANTIBODIES;
HYDROPHOBIC CORE
AB Soluble forms of the human immunodeficiency virus type 1 (HIV-1) primary receptor CD4 (soluble CD4 [sCD4]) have been extensively characterized for a quarter of a century as promising HIV-1 inhibitors, but they have not been clinically successful. By combining a protein cavity-filling strategy and the power of library technology, we identified an engineered cavity-altered single-domain sCD4 (mD1.22) with a unique combination of excellent properties, including broad and potent neutralizing activity, high specificity, stability, solubility, and affinity for the HIV-1 envelope glycoprotein gp120, and small molecular size. To further improve its neutralizing potency and breadth, we generated bispecific multivalent fusion proteins of mD1.22 with another potent HIV-1 inhibitor, an antibody domain (m36.4) that targets the coreceptor-binding site on gp120. The fusion proteins neutralized all HIV-1 isolates tested, with potencies about 10-, 50-, and 200-fold higher than those of the broadly neutralizing antibody VRC01, the U. S. FDA-approved peptide inhibitor T20, and the clinically tested sCD4-Fc fusion protein CD4-Ig, respectively. In addition, they exhibited higher stability and specificity and a lower aggregation propensity than CD4-Ig. Therefore, mD1.22 and related fusion proteins could be useful for HIV-1 prevention and therapy, including eradication of the virus.
C1 [Chen, Weizao; Feng, Yang; Prabakaran, Ponraj; Ying, Tianlei; Wang, Yanping; Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
[Prabakaran, Ponraj; Wang, Yanping] NCI, Basic Res Program, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc,NIH, Frederick, MD 21701 USA.
[Sun, Jianping; He, Yuxian] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China.
[Sun, Jianping; He, Yuxian] Chinese Acad Med Sci, Inst Pathogen Biol, AIDS Res Ctr, Beijing 100730, Peoples R China.
[Sun, Jianping; He, Yuxian] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Macedo, Camila D. S.] Henry M Jackson Fdn, Bethesda, MD USA.
[Macedo, Camila D. S.; Polonis, Victoria R.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA.
RP Chen, WZ (reprint author), NCI, Prot Interact Grp, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21701 USA.
EM chenw3@mail.nih.gov; dimiter.dimitrov@nih.gov
FU Intramural AIDS Targeted Antiviral Program (IATAP) of the National
Institutes of Health (NIH); Intramural Research Program of the NIH;
National Cancer Institute (NCI), Center for Cancer Research; NIH NCI
[NO1-CO-12400]; U.S.-China Program for Biomedical Research Cooperation;
Natural Science Foundation of China [81025009, 81271830]
FX This project was supported by the Intramural AIDS Targeted Antiviral
Program (IATAP) of the National Institutes of Health (NIH), the
Intramural Research Program of the NIH, National Cancer Institute (NCI),
Center for Cancer Research, federal funds from the NIH NCI under
contract number NO1-CO-12400, the U.S.-China Program for Biomedical
Research Cooperation, and grants to Y.H. (81025009 and 81271830) from
the Natural Science Foundation of China.
NR 71
TC 11
Z9 11
U1 1
U2 5
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 2014
VL 88
IS 2
BP 1125
EP 1139
DI 10.1128/JVI.02566-13
PG 15
WC Virology
SC Virology
GA 282SY
UT WOS:000329194900034
PM 24198429
ER
PT J
AU Sun, M
Grigsby, IF
Gorelick, RJ
Mansky, LM
Musier-Forsyth, K
AF Sun, Meng
Grigsby, Iwen F.
Gorelick, Robert J.
Mansky, Louis M.
Musier-Forsyth, Karin
TI Retrovirus-Specific Differences in Matrix and Nucleocapsid
Protein-Nucleic Acid Interactions: Implications for Genomic RNA
Packaging
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GAG MEMBRANE-BINDING; HIV-1 GAG; IN-VITRO;
FLUORESCENCE POLARIZATION; ENCAPSIDATION SIGNAL; CHAPERONE ACTIVITY;
PLASMA-MEMBRANE; ZINC-FINGER; AMINO-ACIDS
AB Retroviral RNA encapsidation involves a recognition event between genomic RNA (gRNA) and one or more domains in Gag. In HIV-1, the nucleocapsid (NC) domain is involved in gRNA packaging and displays robust nucleic acid (NA) binding and chaperone functions. In comparison, NC of human T-cell leukemia virus type 1 (HTLV-1), a deltaretrovirus, displays weaker NA binding and chaperone activity. Mutation of conserved charged residues in the deltaretrovirus bovine leukemia virus (BLV) matrix (MA) and NC domains affects virus replication and gRNA packaging efficiency. Based on these observations, we hypothesized that the MA domain may generally contribute to NA binding and genome encapsidation in deltaretroviruses. Here, we examined the interaction between HTLV-2 and HIV-1 MA proteins and various NAs in vitro. HTLV-2 MA displays higher NA binding affinity and better chaperone activity than HIV-1 MA. HTLV-2 MA also binds NAs with higher affinity than HTLV-2 NC and displays more robust chaperone function. Mutation of two basic residues in HTLV-2 MA alpha-helix II, previously implicated in BLV gRNA packaging, reduces NA binding affinity. HTLV-2 MA binds with high affinity and specificity to RNA derived from the putative packaging signal of HTLV-2 relative to nonspecific NA. Furthermore, an HIV-1 MA triple mutant designed to mimic the basic character of HTLV-2 MA alpha-helix II dramatically improves binding affinity and chaperone activity of HIV-1 MA in vitro and restores RNA packaging to a Delta NC HIV-1 variant in cell-based assays. Taken together, these results are consistent with a role for deltaretrovirus MA proteins in viral RNA packaging.
C1 [Sun, Meng; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retroviral Res, Dept Chem & Biochem, Columbus, OH 43210 USA.
[Sun, Meng; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
[Grigsby, Iwen F.; Mansky, Louis M.] Univ Minnesota, Sch Dent & Med Sch, Inst Mol Virol, Dept Diagnost, Minneapolis, MN USA.
[Grigsby, Iwen F.; Mansky, Louis M.] Univ Minnesota, Sch Dent & Med Sch, Dept Biol Sci & Microbiol, Minneapolis, MN USA.
[Gorelick, Robert J.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Leidos Biomed Res Inc, Frederick, MD USA.
RP Musier-Forsyth, K (reprint author), Ohio State Univ, Ctr Retroviral Res, Dept Chem & Biochem, Columbus, OH 43210 USA.
EM musier@chemistry.ohio-state.edu
FU NIH, National Cancer Institute; Center for Cancer Research; NIH
[GM065056, GM098500]; National Cancer Institute, National Institutes of
Health, [HHSN261200800001E]; Leidos Biomedical Research, Inc.
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research, and by NIH grants
GM065056 (to K.M.-F.) and GM098500 (to L.M.M.). This project has been
funded in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract
HHSN261200800001E with Leidos Biomedical Research, Inc. (R.J.G.).
NR 60
TC 8
Z9 8
U1 0
U2 2
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 2014
VL 88
IS 2
BP 1271
EP 1280
DI 10.1128/JVI.02151-13
PG 10
WC Virology
SC Virology
GA 282SY
UT WOS:000329194900044
PM 24227839
ER
PT J
AU Sunshine, J
Kim, M
Carlson, JM
Heckerman, D
Czartoski, J
Migueles, SA
Maenza, J
McElrath, MJ
Mullins, JI
Frahm, N
AF Sunshine, Justine
Kim, Moon
Carlson, Jonathan M.
Heckerman, David
Czartoski, Julie
Migueles, Stephen A.
Maenza, Janine
McElrath, M. Juliana
Mullins, James I.
Frahm, Nicole
TI Increased Sequence Coverage through Combined Targeting of Variant and
Conserved Epitopes Correlates with Control of HIV Replication
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; IMMUNE-RESPONSES;
LYMPHOCYTE RESPONSE; DISEASE PROGRESSION; PRIMARY INFECTION; TYPE-1
INFECTION; RHESUS-MONKEYS; VIRAL LOAD; ESCAPE
AB A major challenge in the development of an HIV vaccine is that of contending with the extensive sequence variability found in circulating viruses. Induction of HIV-specific T-cell responses targeting conserved regions and induction of HIV-specific T-cell responses recognizing a high number of epitope variants have both been proposed as strategies to overcome this challenge. We addressed the ability of cytotoxic T lymphocytes from 30 untreated HIV-infected subjects with and without control of virus replication to recognize all clade B Gag sequence variants encoded by at least 5% of the sequences in the Los Alamos National Laboratory HIV database (1,300 peptides) using gamma interferon and interleukin-2 (IFN-gamma/IL-2) FluoroSpot analysis. While targeting of conserved regions was similar in the two groups (P = 0.47), we found that subjects with control of virus replication demonstrated marginally lower recognition of Gag epitope variants than subjects with normal progression (P = 0.05). In viremic controllers and progressors, we found variant recognition to be associated with viral load (r = 0.62, P = 0.001). Interestingly, we show that increased overall sequence coverage, defined as the overall proportion of HIV database sequences targeted through the Gag-specific repertoire, is inversely associated with viral load (r = -0.38, P = 0.03). Furthermore, we found that sequence coverage, but not variant recognition, correlated with increased recognition of a panel of clade B HIV founder viruses (r = 0.50, P = 0.004). We propose sequence coverage by HIV Gag-specific immune responses as a possible correlate of protection that may contribute to control of virus replication. Additionally, sequence coverage serves as a valuable measure by which to evaluate the protective potential of future vaccination strategies.
C1 [Sunshine, Justine; McElrath, M. Juliana; Frahm, Nicole] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Kim, Moon; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Maenza, Janine; McElrath, M. Juliana; Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA.
[McElrath, M. Juliana; Mullins, James I.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Carlson, Jonathan M.; Heckerman, David] Microsoft Res, eSci Grp, Los Angeles, CA USA.
[Czartoski, Julie; McElrath, M. Juliana; Frahm, Nicole] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Migueles, Stephen A.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Frahm, N (reprint author), Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
EM nfrahm@fhcrc.org
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [R21AI078809, T32AI007140, P01AI057005,
R01AI047086, UM1AI068618]
FX Research reported in this publication was supported by the National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health under award numbers R21AI078809, T32AI007140, P01AI057005,
R01AI047086, and UM1AI068618.
NR 68
TC 5
Z9 5
U1 0
U2 2
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 2014
VL 88
IS 2
BP 1354
EP 1365
DI 10.1128/JVI.02361-13
PG 12
WC Virology
SC Virology
GA 282SY
UT WOS:000329194900051
PM 24227851
ER
PT J
AU Liu, XQ
Cohen, JI
AF Liu, XueQiao
Cohen, Jeffrey I.
TI Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and
Delays Plaque Formation in Virus-Infected Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PROTEIN-KINASE; BLOCKS APOPTOSIS; GLYCOPROTEIN-D; BAD; PHOSPHORYLATION;
SURVIVAL; ERK; PATHWAY; ACTIVATION; RESISTANCE
AB Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wildtype cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication.
C1 [Liu, XueQiao; Cohen, Jeffrey I.] NIH, Infect Dis Lab, Med Virol Sect, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Infect Dis Lab, Med Virol Sect, Bldg 10, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases.
NR 61
TC 2
Z9 3
U1 0
U2 4
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 2014
VL 88
IS 2
BP 1381
EP 1388
DI 10.1128/JVI.01695-13
PG 8
WC Virology
SC Virology
GA 282SY
UT WOS:000329194900053
PM 24227856
ER
PT J
AU Hillengass, J
Weber, MA
Kilk, K
Listl, K
Wagner-Gund, B
Hillengass, M
Hielscher, T
Farid, A
Neben, K
Delorme, S
Landgren, O
Goldschmidt, H
AF Hillengass, J.
Weber, M-A
Kilk, K.
Listl, K.
Wagner-Gund, B.
Hillengass, M.
Hielscher, T.
Farid, A.
Neben, K.
Delorme, S.
Landgren, O.
Goldschmidt, H.
TI Prognostic significance of whole-body MRI in patients with monoclonal
gammopathy of undetermined significance
SO LEUKEMIA
LA English
DT Article
DE monoclonal gammopathy of undetermined significance; whole body magnetic
resonance imaging; prognosis; focal lesions
ID ASYMPTOMATIC MULTIPLE-MYELOMA; BONE-MARROW; SIGNIFICANCE MGUS; COMPETING
RISK; PROGRESSION; DISEASE; INFILTRATION; ENHANCEMENT; POPULATION;
PATTERNS
AB Radiological skeletal survey or computed tomography are currently applied to assess bone diseases in patients with monoclonal plasma cell disorders. Whole-body magnetic resonance imaging (whole-body MRI) allows detecting the infiltration of clonal cells in nearly the whole bone marrow compartment even before bone destruction has occurred. Those MRI results (i.e., patterns of bone marrow infiltration) have been demonstrated to be of prognostic significance in patients with symptomatic as well as asymptomatic multiple myeloma. We have therefore analyzed the findings of whole-body MRI in 137 consecutive individuals with monoclonal gammopathy of undetermined significance (MGUS). A focal infiltration pattern was detected in 23.4% of patients. Presence and number of focal lesions as well as value of M-Protein were of independent prognostic significance for progression into a symptomatic disease requiring systemic treatment (P = 0.02; P<0.0001 and P = 0.0005, respectively). Lower homogeneous signal intensities in T1-weighted images were related to a physiologically higher bone marrow cellularity in younger individuals (P = 0.002). We conclude that whole-body MRI identifies patients with focal accumulations of presumably monoclonal cells in bone marrow with prognostic impact concerning the risk of progression into symptomatic disease.
C1 [Hillengass, J.; Wagner-Gund, B.; Hillengass, M.; Farid, A.; Neben, K.; Goldschmidt, H.] Heidelberg Univ, Dept Hematol & Oncol, D-69120 Heidelberg, Germany.
[Hillengass, J.; Delorme, S.] German Canc Res Ctr, Dept Radiol, Heidelberg, Germany.
[Weber, M-A; Kilk, K.; Listl, K.] Heidelberg Univ, Dept Diagnost & Intervent Radiol, D-69120 Heidelberg, Germany.
[Hielscher, T.] German Canc Res Ctr, Dept Biostat, Heidelberg, Germany.
[Landgren, O.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Goldschmidt, H.] Natl Ctr Tumor Dis, Heidelberg, Germany.
RP Hillengass, J (reprint author), Heidelberg Univ, Dept Hematol & Oncol, Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
EM Jens.hillengass@med.uni-heidelberg.de
RI Weber, Marc-Andre/C-4452-2016;
OI Delorme, Stefan/0000-0002-1000-2582
FU International Myeloma Foundation; Dietmar Hopp Stiftung; German Research
Foundation [SFB Transregio 79]
FX Parts of this study were supported by grants from the International
Myeloma Foundation, the Dietmar Hopp Stiftung and the German Research
Foundation (SFB Transregio 79).
NR 33
TC 23
Z9 23
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD JAN
PY 2014
VL 28
IS 1
BP 174
EP 178
DI 10.1038/leu.2013.244
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA 286CD
UT WOS:000329441200018
PM 23958921
ER
PT J
AU Miettinen, M
AF Miettinen, Markku
TI Smooth muscle tumors of soft tissue and non-uterine viscera: biology and
prognosis
SO MODERN PATHOLOGY
LA English
DT Article
DE bone and soft tissue; leiomyoma; leiomyosarcoma
ID INFERIOR VENA-CAVA; EPSTEIN-BARR-VIRUS; GASTROINTESTINAL STROMAL TUMORS;
OF-THE-LITERATURE; LEIOMYOMATOSIS PERITONEALIS DISSEMINATA;
ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BENIGN METASTASIZING LEIOMYOMA;
EPITHELIAL MEMBRANE ANTIGEN; CLINICOPATHOLOGICAL ANALYSIS;
RETROPERITONEAL LEIOMYOSARCOMAS
AB Smooth muscle tumors are here considered an essentially dichotomous group composed of benign leiomyomas and malignant leiomyosarcomas. Soft tissue smooth muscle tumors with both atypia and mitotic activity are generally diagnosed lelomyosarcomas acknowledging potential for metastasis. However, lesions exist that cannot be comfortably placed in either category, and in such cases the designation 'smooth muscle tumor of uncertain biologic potential' is appropriate. The use of this category is often necessary with limited sampling, such as needle core biopsies. Benign smooth muscle tumors include smooth muscle hamartoma and angioleiomyoma. A specific category of leiomyomas are estrogen-receptor positive ones in women. These are similar to uterine leiomyomas and can occur anywhere in the abdomen and abdominal wall. Leiomyosarcomas can occur at any site, although are more frequent in the retroperitoneum and proximal extremities. They are recognized by likeness to smooth muscle cells but can undergo pleomorphic evolution ('dedifferentiation'). Presence of smooth muscle actin is nearly uniform and desmin-positivity usual. This and the lack of KIT expression separate leiomyosarcoma from GIST, an important problem in abdominal soft tissues. EBV-associated smooth muscle tumors are a specific subcategory occurring in AIDS or post-transplant patients. These tumors can have incomplete smooth muscle differentiation but show nuclear EBER as a diagnostic feature. In contrast to many other soft tissue tumors, genetics of smooth muscle tumors are poorly understood and such diagnostic testing is not yet generally applicable in this histogenetic group. Leiomyosarcomas are known to be genetically complex, often showing 'chaotic' karyotypes including aneuploidy or polyploidy, and no recurrent tumor-specific translocations have been detected.
C1 NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Miettinen, M (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Room 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI
FX This work has been supported as a part of NCI's intramural research
program.
NR 85
TC 13
Z9 13
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD JAN
PY 2014
VL 27
SU 1
BP S17
EP S29
DI 10.1038/modpathol.2013.178
PG 13
WC Pathology
SC Pathology
GA 285TW
UT WOS:000329418900002
PM 24384850
ER
PT J
AU Rees, E
Kirov, G
Sanders, A
Walters, JTR
Chambert, KD
Shi, J
Szatkiewicz, J
O'Dushlaine, C
Richards, AL
Green, EK
Jones, I
Davies, G
Legge, SE
Moran, JL
Pato, C
Pato, M
Genovese, G
Levinson, D
Duan, J
Moy, W
Goring, HHH
Morris, D
Cormican, P
Kendler, KS
O'Neill, FA
Riley, B
Gill, M
Corvin, A
Craddock, N
Sklar, P
Hultman, C
Sullivan, PF
Gejman, PV
McCarroll, SA
O'Donovan, MC
Owen, MJ
AF Rees, E.
Kirov, G.
Sanders, A.
Walters, J. T. R.
Chambert, K. D.
Shi, J.
Szatkiewicz, J.
O'Dushlaine, C.
Richards, A. L.
Green, E. K.
Jones, I.
Davies, G.
Legge, S. E.
Moran, J. L.
Pato, C.
Pato, M.
Genovese, G.
Levinson, D.
Duan, J.
Moy, W.
Goering, H. H. H.
Morris, D.
Cormican, P.
Kendler, K. S.
O'Neill, F. A.
Riley, B.
Gill, M.
Corvin, A.
Craddock, N.
Sklar, P.
Hultman, C.
Sullivan, P. F.
Gejman, P. V.
McCarroll, S. A.
O'Donovan, M. C.
Owen, M. J.
CA Wellcome Trust Case Control Consor
TI Evidence that duplications of 22q11.2 protect against schizophrenia
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE 22q11.2; CNV; duplication; protective; schizophrenia
ID CARDIO-FACIAL SYNDROME; COPY NUMBER VARIATION; MICRODUPLICATION 22Q11.2;
DELETION SYNDROME; VARIANTS; ADULTS; COMMON; RISK
AB A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2-the reciprocal of the well-known, risk-inducing deletion of this locus-are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR = 0.17, P - 0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.
C1 [Rees, E.; Kirov, G.; Walters, J. T. R.; Richards, A. L.; Green, E. K.; Jones, I.; Davies, G.; Legge, S. E.; Craddock, N.; O'Donovan, M. C.; Owen, M. J.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales.
[Sanders, A.; Duan, J.; Moy, W.; Gejman, P. V.] NorthShore Univ HealthSyst, Dept Psychiat & Behav Sci, Evanston, IL USA.
[Sanders, A.; Duan, J.; Gejman, P. V.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Chambert, K. D.; O'Dushlaine, C.; Moran, J. L.; Genovese, G.; McCarroll, S. A.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA.
[Shi, J.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA.
[Szatkiewicz, J.; Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Green, E. K.] Univ Plymouth, Sch Biomed & Biol Sci, Plymouth PL4 8AA, Devon, England.
[Pato, C.; Pato, M.] Univ So Calif, Zilkha Neurogenet Inst, Dept Psychiat & Behav Sci, Los Angeles, CA USA.
[Levinson, D.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Goering, H. H. H.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
[Morris, D.; Cormican, P.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, Inst Mol Med, Dept Psychiat, Dublin 2, Ireland.
[Morris, D.; Cormican, P.; Gill, M.; Corvin, A.] Univ Dublin Trinity Coll, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin 2, Ireland.
[Kendler, K. S.; Riley, B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat & Human Genet, Richmond, VA USA.
[O'Neill, F. A.] Queens Univ, Dept Psychiat, Belfast, Antrim, North Ireland.
[Sklar, P.] Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA.
[Hultman, C.; Sullivan, P. F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Karolinska, Sweden.
[Sullivan, P. F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
RP Owen, MJ (reprint author), Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Hadyn Ellis Bldg Maindy Rd, Cardiff CF24 4HQ, S Glam, Wales.
EM ODonovanMC@cf.ac.uk; OwenMJ@cf.ac.uk
OI Gill, Michael/0000-0003-0206-5337; Corvin, Aiden/0000-0001-6717-4089;
O'Donovan, Michael/0000-0001-7073-2379; Morris,
Derek/0000-0002-3413-570X; Moran, Jennifer/0000-0002-5664-4716; Walters,
James/0000-0002-6980-4053; O'Neill, Francis Anthony/0000-0002-7531-7657
FU Stanley Center for Psychiatric Research; MRC/Welsh Assembly Government;
British Medical Association; Medical Research Council (MRC) Centre
[G0800509, G0801418]; European Community [HEALTH-F2-2010-241909]; NIMH
[R01 MH077139, R01 MH095034, MH 41953, MH083094]; Karolinska Institutet;
Karolinska University Hospital; Swedish Research Council; Swedish County
Council; Soderstrom Konigska Foundation; Netherlands Scientific
Organization [NWO 645-000-003]; Wellcome Trust Case Control Consortium 2
project [085475/B/08/Z, 085475/Z/08/Z]; Wellcome Trust [072894/Z/03/Z,
090532/Z/09/Z, 075491/Z/04/B]; Science Foundation Ireland
[08/IN.1/B1916]; National Institutes of Health [HHSN268200782096C]; Gene
Environment Association Studies (GENEVA) Coordinating Center [U01
HG004446]; Collaborative Genetic Study of Nicotine Dependence (COGEND)
[P01 CA089392]; University of Wisconsin Transdisciplinary Tobacco Use
Research Center [P50 DA019706, P50 CA084724]; National Institutes of
Health, Bethesda, MD, USA [R01 EY020483]; [RC2MH090030];
[R01MH094091]; [1 x 01 HG005274-01]; [3P50CA093459]; [5P50CA097007];
[5R01ES011740]; [5R01CA133996]
FX The 6882 schizophrenia cases from the discovery sample were genotyped at
the Broad Institute and funded by a philanthropic gift to the Stanley
Center for Psychiatric Research. We thank the participants and
clinicians who took part in the Cardiff COGS study. This work was
supported by a clinical research fellowship to JW from the MRC/Welsh
Assembly Government and the Margaret Temple Award from the British
Medical Association. We acknowledge Andrew Iles, David Parslow, Carissa
Philipart and Sophie Canton for their work in recruitment, interviewing
and rating. For the CLOZUK sample, we thank Novartis for their guidance
and co-operation. We also thank staff at The Doctor's Laboratory, in
particular Lisa Levett and Andrew Levett, for help and advice regarding
sample acquisition. We acknowledge Kiran Mantripragada, Lesley Bates,
Catherine Bresner and Lucinda Hopkins for laboratory sample management.
The work at Cardiff University was funded by the Medical Research
Council (MRC) Centre (G0800509) and Program Grants (G0801418), the
European Community's Seventh Framework Programme (HEALTH-F2-2010-241909
(Project EU-GEI) and a PhD to ER. Funding support for the Swedish study
was provided by NIMH R01 MH077139 (P Sullivan), NIMH R01 MH095034 (P
Sklar), the Stanley Center for Psychiatric Research, the Karolinska
Institutet, Karolinska University Hospital, the Swedish Research
Council, an ALF grant from Swedish County Council, the Soderstrom
Konigska Foundation and the Netherlands Scientific Organization (NWO
645-000-003). For Irish/WTCCC2 study, funding was provided by the
Wellcome Trust Case Control Consortium 2 project (085475/B/08/Z and
085475/Z/08/Z), the Wellcome Trust (072894/Z/03/Z, 090532/Z/09/Z and
075491/Z/04/B), NIMH grants (MH 41953 and MH083094) and Science
Foundation Ireland (08/IN.1/B1916). The LCL expression data was
generated with grant support from RC2MH090030 and R01MH094091. The
authors acknowledge the contribution of data from outside sources: (1)
Genetic Architecture of Smoking and Smoking Cessation accessed through
dbGAP: Study Accession: phs000404.v1.p1. Funding support for genotyping,
which was performed at the Center for Inherited Disease Research (CIDR),
was provided by 1 x 01 HG005274-01. CIDR is fully funded through a
federal contract from the National Institutes of Health to The Johns
Hopkins University, contract number HHSN268200782096C. Assistance with
genotype cleaning, as well as with general study coordination, was
provided by the Gene Environment Association Studies (GENEVA)
Coordinating Center (U01 HG004446). Funding support for collection of
data sets and samples was provided by the Collaborative Genetic Study of
Nicotine Dependence (COGEND; P01 CA089392) and the University of
Wisconsin Transdisciplinary Tobacco Use Research Center (P50 DA019706,
P50 CA084724). (2) High Density SNP Association Analysis of Melanoma:
Case-Control and Outcomes Investigation, dbGaP Study Accession:
phs000187.v1.p1: Research support to collect data and develop an
application to support this project was provided by 3P50CA093459,
5P50CA097007, 5R01ES011740 and 5R01CA133996. (3) Genetic Epidemiology of
Refractive Error in the KORA (Kooperative Gesundheitsforschung in der
Region Augsburg) Study, dbGaP Study Accession: phs000303.v1.p1.
Principal Investigators: Dwight Stambolian, University of Pennsylvania,
Philadelphia, PA, USA; H Erich Wichmann, Institut fur Humangenetik,
Helmholtz-Zentrum Munchen, Germany, National Eye Institute, National
Institutes of Health, Bethesda, MD, USA.; Funded by R01 EY020483,
National Institutes of Health, Bethesda, MD, USA. (4) WTCCC2 project
samples from National Blood Doners (NBS) Cohort, EGAD00000000024. WTCCC2
project samples from 1958 British Birth Cohort, EGAD00000000022.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JAN
PY 2014
VL 19
IS 1
BP 37
EP 40
DI 10.1038/mp.2013.156
PG 4
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 279MS
UT WOS:000328964700010
PM 24217254
ER
PT J
AU Uhl, GR
Walther, D
Musci, R
Fisher, C
Anthony, JC
Storr, CL
Behm, FM
Eaton, WW
Ialongo, N
Rose, JE
AF Uhl, G. R.
Walther, D.
Musci, R.
Fisher, C.
Anthony, J. C.
Storr, C. L.
Behm, F. M.
Eaton, W. W.
Ialongo, N.
Rose, J. E.
TI Smoking quit success genotype score predicts quit success and distinct
patterns of developmental involvement with common addictive substances
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE cannabis; complex genetics; development; genetic scores; predictive
validity; smoking
ID GENOME-WIDE ASSOCIATION; SAMPLE-SIZE CALCULATIONS; CESSATION SUCCESS;
POLYSUBSTANCE ABUSERS; NICOTINE REPLACEMENT; CANCER RISK; DISEASE;
POLYMORPHISMS; GENES; TRIAL
AB Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P = 0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P = 0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P = 0.001). These results indicate that: (a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.
C1 [Uhl, G. R.; Walther, D.; Fisher, C.] NIDA, NIH IRP, Mol Neurobiol Branch, Baltimore, MD 21224 USA.
[Musci, R.; Eaton, W. W.; Ialongo, N.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Anthony, J. C.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Storr, C. L.] Univ Maryland, Sch Nursing, Dept Family & Community Hlth, Baltimore, MD 21201 USA.
[Storr, C. L.; Behm, F. M.; Rose, J. E.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA.
[Storr, C. L.; Behm, F. M.; Rose, J. E.] Duke Univ, Ctr Nicotine & Smoking Cessat Res, Durham, NC 27706 USA.
RP Uhl, GR (reprint author), NIDA, NIH IRP, Mol Neurobiol Branch, Box 5180, Baltimore, MD 21224 USA.
EM guhl@intra.nida.nih.gov
FU National Institutes of Health (NIH)-Intramural Research Program,
National Institute on Drug Abuse, Department of Health and Human
Services; Philip Morris, USA; NIDA [R01-DA009897, 4R37DA011796-11]
FX This study was supported by the National Institutes of Health
(NIH)-Intramural Research Program, National Institute on Drug Abuse,
Department of Health and Human Services (Dr Uhl); a grant to Duke
University (PI, Dr Rose) from Philip Morris, USA for the work performed
before January 2012; NIDA grants R01-DA009897 (WE) and 4R37DA011796-11
(NI). The funders had no role in the planning or execution of the study,
data analysis or publication of results. We are grateful to TGEN
investigators for generous access to Alzheimer's disease GWAS genotype
data and D Sisto for its analysis, to E Westman for assistance with the
smoking cessation clinical trial, for each of the prevention study
investigators, especially S Kellam, for the sustained cooperation of the
study participants and for help and thoughtful advice from C Johnson, J
Schroder, P Zandi and K Masyn. The underlying smoking cessation clinical
trial was registered with clinicaltrials.gov (NCT00894166).
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JAN
PY 2014
VL 19
IS 1
BP 50
EP 54
DI 10.1038/mp.2012.155
PG 5
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 279MS
UT WOS:000328964700012
PM 23128154
ER
PT J
AU Lohoff, FW
Hodge, R
Narasimhan, S
Nall, A
Ferraro, TN
Mickey, BJ
Heitzeg, MM
Langenecker, SA
Zubieta, JK
Bogdan, R
Nikolova, YS
Drabant, E
Hariri, AR
Bevilacqua, L
Goldman, D
Doyle, GA
AF Lohoff, F. W.
Hodge, R.
Narasimhan, S.
Nall, A.
Ferraro, T. N.
Mickey, B. J.
Heitzeg, M. M.
Langenecker, S. A.
Zubieta, J-K
Bogdan, R.
Nikolova, Y. S.
Drabant, E.
Hariri, A. R.
Bevilacqua, L.
Goldman, D.
Doyle, G. A.
TI Functional genetic variants in the vesicular monoamine transporter 1
modulate emotion processing
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE amygdala; bipolar disorder; medial PFC; schizophrenia; SLC18A1
ID AMYGDALA ACTIVATION; AMINE TRANSPORTER; MAJOR DEPRESSION; BIPOLAR
DISORDER; CHROMOSOME 8P; SCHIZOPHRENIA; ASSOCIATION; BRAIN; AMPHETAMINE;
RESERPINE
AB Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits and risk for psychopathology.
C1 [Lohoff, F. W.; Hodge, R.; Narasimhan, S.; Nall, A.; Ferraro, T. N.; Doyle, G. A.] Univ Penn, Sch Med, Ctr Neurobiol & Behav, Translat Res Labs,Dept Psychiat, Philadelphia, PA 19104 USA.
[Mickey, B. J.; Heitzeg, M. M.; Langenecker, S. A.; Zubieta, J-K] Univ Michigan, Dept Psychiat, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA.
[Bogdan, R.; Nikolova, Y. S.; Hariri, A. R.] Duke Univ, Inst Genome Sci & Policy, Dept Psychol & Neurosci, Durham, NC USA.
[Bogdan, R.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
[Drabant, E.] 23andMe, Mountain View, CA USA.
[Bevilacqua, L.; Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
RP Lohoff, FW (reprint author), Univ Penn, Sch Med, Ctr Neurobiol & Behav, Translat Res Labs,Dept Psychiat, 125 South 31st St,Room 2213, Philadelphia, PA 19104 USA.
EM lohoff@mail.med.upenn.edu
RI Mickey, Brian/J-1756-2014; Goldman, David/F-9772-2010; Lohoff,
Falk/M-7951-2016;
OI Mickey, Brian/0000-0002-7847-7680; Goldman, David/0000-0002-1724-5405;
Bogdan, Ryan/0000-0002-1430-1045; Narasimhan, Sneha/0000-0002-1665-9681
FU National Institutes of Health [NIH K08MH080372]; NCRR [UL1 RR 024986];
NIMH [P01 MH 42251, R25 MH 6374, K23 MH 074459]; NIDA [R01 DA 016423,
R01 DA 022520, R01 DA 026222, R01 DA 031579]; Phil F Jenkins Research
Fund
FX This work was supported by the Center for Neurobiology and Behavior,
Department of Psychiatry, University of Pennsylvania. Financial support
is gratefully acknowledged from National Institutes of Health Grants
(NIH K08MH080372 to FWL), NCRR (UL1 RR 024986), NIMH (P01 MH 42251, R25
MH 6374 and K23 MH 074459), NIDA (R01 DA 016423 and R01 DA 022520, and
026222 and 031579) and the Phil F Jenkins Research Fund.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JAN
PY 2014
VL 19
IS 1
BP 129
EP 139
DI 10.1038/mp.2012.193
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 279MS
UT WOS:000328964700022
PM 23337945
ER
PT J
AU Sellers, SE
Dumitriu, B
Morgan, MJ
Hughes, WM
Wu, CO
Raghavarchari, N
Yang, YQ
Uchida, N
Tisdale, JF
An, DS
Chen, IS
Hematti, P
Donahue, RE
LaRochelle, A
Young, NS
Calado, RT
Dunbar, CE
AF Sellers, Stephanie E.
Dumitriu, Bogdan
Morgan, Mary J.
Hughes, William M.
Wu, Colin O.
Raghavarchari, Nalini
Yang, Yanqin
Uchida, Naoya
Tisdale, John F.
An, Dong S.
Chen, Irvin S.
Hematti, Peiman
Donahue, Robert E.
LaRochelle, Andre
Young, Neal S.
Calado, Rodrigo T.
Dunbar, Cynthia E.
TI No Impact of Lentiviral Transduction on Hematopoietic Stem/Progenitor
Cell Telomere Length or Gene Expression in the Rhesus Macaque Model
SO MOLECULAR THERAPY
LA English
DT Article
ID RETROVIRAL VECTOR INTEGRATION; STEM-CELLS; BLOOD-CELLS; TRANSGENE
EXPRESSION; REPOPULATING CELLS; NONHUMAN-PRIMATES; SITE SELECTION;
IN-VIVO; THERAPY; SCID-X1
AB The occurrence of clonal perturbations and leukemia in patients transplanted with gamma-retroviral (RV) vector-transduced autologous hematopoietic stem and progenitor cells (HSPCs) has stimulated extensive investigation, demonstrating that proviral insertions may perturb adjacent proto-oncogene expression. Although enhancer-deleted lentiviruses are less likely to result in insertional oncogenesis, there is evidence that they may perturb transcript splicing, and one patient with a benign clonal expansion of lentivirally transduced HPSC has been reported. The rhesus macaque model provides an opportunity for informative long-term analysis to ask whether transduction impacts on long-term HSPC properties. We used two techniques to examine whether lentivirally transduced HSPCs from eight rhesus macaques transplanted 1-13.5 years previously are perturbed at a population level, comparing telomere length as a measure of replicative history and gene expression profile of vector positive versus vector negative cells. There were no differences in telomere lengths between sorted GFP(+) and GFP(-) blood cells, suggesting that lentiviral (LV) transduction did not globally disrupt replicative patterns. Bone marrow GFP(+) and GFP(-) CD34(+) cells showed no differences in gene expression using unsupervised and principal component analysis. These studies did not uncover any global long-term perturbation of proliferation, differentiation, or other important functional parameters of transduced HSPCs in the rhesus macaque model.
C1 [Sellers, Stephanie E.; Dumitriu, Bogdan; Morgan, Mary J.; Hughes, William M.; Donahue, Robert E.; LaRochelle, Andre; Young, Neal S.; Calado, Rodrigo T.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Raghavarchari, Nalini; Yang, Yanqin] NHLBI, DNA Sequencing & Genom Core, NIH, Bethesda, MD 20892 USA.
[Uchida, Naoya; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA.
[An, Dong S.; Chen, Irvin S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Hematti, Peiman] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Room 4E-5232,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
RI Calado, Rodrigo/G-2619-2011
FU intramural research program of the NHLBI
FX The authors thank Keyvan Kevanfar for flow cytometric sorting, and Mark
Metzger, Alan Krouse, Barrington Thompson, and Sandra Price for
excellent animal care. Funding for these studies was provided by the
intramural research program of the NHLBI. The authors declared no
conflict of interest.
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD JAN
PY 2014
VL 22
IS 1
BP 52
EP 58
DI 10.1038/mt.2013.168
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 282ZI
UT WOS:000329213500008
PM 23863881
ER
PT J
AU Johnson, TR
Rangel, D
Graham, BS
Brough, DE
Gall, JG
AF Johnson, Teresa R.
Rangel, David
Graham, Barney S.
Brough, Douglas E.
Gall, Jason G.
TI Genetic Vaccine for Respiratory Syncytial Virus Provides Protection
Without Disease Potentiation
SO MOLECULAR THERAPY
LA English
DT Article
ID COTTON RATS; NEUTRALIZING ANTIBODIES; INTRANASAL IMMUNIZATION; CANDIDATE
VACCINE; YOUNG-CHILDREN; BALB/C MICE; SUBGROUP-B; F-PROTEIN; IN-VITRO;
T-CELLS
AB Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained >= 24 weeks and RSV-specific CD8(+) and CD4(+) T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing.
C1 [Johnson, Teresa R.; Rangel, David; Brough, Douglas E.; Gall, Jason G.] GenVec Inc, Gaithersburg, MD 20878 USA.
[Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Gall, JG (reprint author), GenVec Inc, 65 West Watkins Mill Rd, Gaithersburg, MD 20878 USA.
EM jgall@genvec.com
FU NIH [R43AI075686-01]; GenVec; National Institutes of Health, National
Institute of Allergy and Infectious Diseases
FX We thank Grant Liao, Emmanuella Eastman, Grace Lee, Karen Tressler,
Valerie Moore, and Damador EttyReddy for excellent technical assistance
as well as Jorge Blanco and Kevin Yim (Sigmovir) for expert advice and
histopathology review. The work was funded by NIH grant R43AI075686-01
and GenVec. T.R.J, D.R., D.E.B., and J.G.G. were employees of GenVec, a
for-profit corporation, and hold stock interests in the company. B.S.G.
and T.R.J. are named on a patent application for the F antigen construct
expressed by the rAd vectors, and B. S. G. is supported by intramural
funding from the National Institutes of Health, National Institute of
Allergy and Infectious Diseases. The authors declared no conflict of
interest.
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD JAN
PY 2014
VL 22
IS 1
BP 196
EP 205
DI 10.1038/mt.2013.142
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 282ZI
UT WOS:000329213500023
PM 23752342
ER
PT J
AU McGray, AJR
Hallett, R
Bernard, D
Swift, SL
Zhu, ZQ
Teoderascu, F
VanSeggelen, H
Hassell, JA
Hurwitz, AA
Wan, YH
Bramson, JL
AF McGray, A. J. Robert
Hallett, Robin
Bernard, Dannie
Swift, Stephanie L.
Zhu, Ziqiang
Teoderascu, Florentina
VanSeggelen, Heather
Hassell, John A.
Hurwitz, Arthur A.
Wan, Yonghong
Bramson, Jonathan L.
TI Immunotherapy-induced CD8(+) T Cells Instigate Immune Suppression in the
Tumor
SO MOLECULAR THERAPY
LA English
DT Article
ID RESISTANT PROSTATE-CANCER; MELANOMA PATIENTS; OVARIAN-CANCER; ANTIGEN;
VACCINATION; VARIANTS; VACCINES; TRIAL; LYMPHOCYTES; RECRUITMENT
AB Despite clear evidence of immunogenicity, cancer vaccines only provide a modest clinical benefit. To evaluate the mechanisms that limit tumor regression following vaccination, we have investigated the weak efficacy of a highly immunogenic experimental vaccine using a murine melanoma model. We discovered that the tumor adapts rapidly to the immune attack instigated by tumor-specific CD8(+) T cells in the first few days following vaccination, resulting in the upregulation of a complex set of biological networks, including multiple immunosuppressive processes. This rapid adaptation acts to prevent sustained local immune attack, despite continued infiltration by increasing numbers of tumor-specific T cells. Combining vaccination with adoptive transfer of tumor-specific T cells produced complete regression of the treated tumors but did not prevent the adaptive immunosuppression. In fact, the adaptive immunosuppressive pathways were more highly induced in regressing tumors, commensurate with the enhanced level of immune attack. Examination of tumor infiltrating T-cell functionality revealed that the adaptive immunosuppression leads to a progressive loss in T-cell function, even in tumors that are regressing. These novel observations that T cells produced by therapeutic intervention can instigate a rapid adaptive immunosuppressive response within the tumor have important implications for clinical implementation of immunotherapies.
C1 [McGray, A. J. Robert; Hallett, Robin; Bernard, Dannie; Swift, Stephanie L.; Teoderascu, Florentina; VanSeggelen, Heather; Hassell, John A.; Wan, Yonghong; Bramson, Jonathan L.] McMaster Univ, McMaster Immunol Res Ctr, Hamilton, ON L8N 3Z5, Canada.
[Zhu, Ziqiang; Hurwitz, Arthur A.] NCI, Canc & Inflammat Program, FCRF, CCR,NIH, Frederick, MD 21701 USA.
RP Bramson, JL (reprint author), McMaster Univ, McMaster Immunol Res Ctr, 1200 Main St West, Hamilton, ON L8N 3Z5, Canada.
EM bramsonj@mcmaster.ca
FU Terry Fox Foundation; Canadian Institutes for Health Research
FX This work was supported by funds from the Terry Fox Foundation. D.B. was
supported by a scholarship from the Canadian Institutes for Health
Research. The authors declared no conflict of interest.
NR 45
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U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD JAN
PY 2014
VL 22
IS 1
BP 206
EP 218
DI 10.1038/mt.2013.255
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 282ZI
UT WOS:000329213500024
PM 24196579
ER
PT S
AU Iantorno, S
Gori, K
Goldman, N
Gil, M
Dessimoz, C
AF Iantorno, Stefano
Gori, Kevin
Goldman, Nick
Gil, Manuel
Dessimoz, Christophe
BE Russell, DJ
TI Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple
Sequence Alignment
SO MULTIPLE SEQUENCE ALIGNMENT METHODS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Multiple sequence alignment; Benchmarking; Phylogenetic; Protein
structure; Sequence evolution; Consistency; Homology
ID HIGH-THROUGHPUT; EVOLUTION; PROGRAMS; SIMULATION; CHALLENGES; ACCURACY;
DATABASE; QUALITY; GAPS; TECHNOLOGY
AB Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies-based on simulation, consistency, protein structure, and phylogeny-and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application-with a keen awareness of the assumptions underlying each benchmarking strategy.
C1 [Iantorno, Stefano] Wellcome Trust Sanger Inst, Cambridge, England.
[Iantorno, Stefano] NIAID, NIH, Bethesda, MD 20892 USA.
[Gori, Kevin; Goldman, Nick; Dessimoz, Christophe] EMBL European Bioinformat Inst, Cambridge, England.
[Gil, Manuel] Univ Vienna, Med Univ Vienna, Max F Perutz Labs, Ctr Integrat Bioinformat Vienna, Vienna, Austria.
RP Iantorno, S (reprint author), Wellcome Trust Sanger Inst, Cambridge, England.
OI Gori, Kevin/0000-0001-7975-4275; Goldman, Nick/0000-0001-8486-2211;
Dessimoz, Christophe/0000-0002-2170-853X
NR 50
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U1 1
U2 10
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-62703-645-0; 978-1-62703-646-7
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1079
BP 59
EP 73
DI 10.1007/978-1-62703-646-7_4
D2 10.1007/978-1-62703-646-7
PG 15
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA BJJ02
UT WOS:000328376500005
PM 24170395
ER
PT J
AU Anderson, KG
Mayer-Barber, K
Sung, H
Beura, L
James, BR
Taylor, JJ
Qunaj, L
Griffith, TS
Vezys, V
Barber, DL
Masopust, D
AF Anderson, Kristin G.
Mayer-Barber, Katrin
Sung, Heungsup
Beura, Lalit
James, Britnie R.
Taylor, Justin J.
Qunaj, Lindor
Griffith, Thomas S.
Vezys, Vaiva
Barber, Daniel L.
Masopust, David
TI Intravascular staining for discrimination of vascular and tissue
leukocytes
SO NATURE PROTOCOLS
LA English
DT Article
ID MEMORY T-CELLS; DENDRITIC CELLS; NONLYMPHOID TISSUE; LYMPHOID-TISSUES;
LOCAL IMMUNITY; B-CELLS; LUNG; MIGRATION; INFECTION; SUBSETS
AB Characterization of the cellular participants in tissue immune responses is crucial to understanding infection, cancer, autoimmunity, allergy, graft rejection and other immunological processes. Previous reports indicate that leukocytes in lung vasculature fail to be completely removed by perfusion. Several studies suggest that intravascular staining may discriminate between tissue-localized and blood-borne cells in the mouse lung. Here we outline a protocol for the validation and use of intravascular staining to define innate and adaptive immune cells in mice. We demonstrate application of this protocol to leukocyte analyses in many tissues and we describe its use in the contexts of lymphocytic choriomeningitis virus and Mycobacterium tuberculosis infections or solid tumors. Intravascular staining and organ isolation usually takes 5-30 min per mouse, with additional time required for any subsequent leukocyte isolation, staining and analysis. In summary, this simple protocol should help enable interpretable analyses of tissue immune responses.
C1 [Anderson, Kristin G.; Sung, Heungsup; Beura, Lalit; Taylor, Justin J.; Qunaj, Lindor; Vezys, Vaiva; Masopust, David] Univ Minnesota, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
[Mayer-Barber, Katrin] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[James, Britnie R.; Griffith, Thomas S.] Univ Minnesota, Masonic Canc Ctr, Ctr Immunol, Dept Urol, Minneapolis, MN 55455 USA.
[Barber, Daniel L.] NIAID, T Lymphocyte Biol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Masopust, D (reprint author), Univ Minnesota, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
EM masopust@umn.edu
OI Vezys, Vaiva/0000-0002-2520-809X; Qunaj, Lindor/0000-0001-8461-8374
FU US NIH grant [AI084913-01, DP2 OD006467, CA109446]; Arnold and Mabel
Beckman Foundation; National Institute of Dental and Craniofacial
Research [T90DE022732]; National Institute of Allergy and Infectious
Diseases Intramural Program
FX This study was supported by US NIH grant nos. AI084913-01 and DP2
OD006467 (D.M.), the Arnold and Mabel Beckman Foundation (D.M.), grant
no. T90DE022732 from the National Institute of Dental and Craniofacial
Research (K.G.A.), the National Institute of Allergy and Infectious
Diseases Intramural Program (K.M.-B. and D.L.B.) and US NIH grant no.
CA109446 (T.S.G.). We thank the University of Minnesota Center for
Immunology Imaging Core, the University of Minnesota Imaging Center and
the Flow Cytometry Core.
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U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD JAN
PY 2014
VL 9
IS 1
BP 209
EP 222
DI 10.1038/nprot.2014.005
PG 14
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 282QD
UT WOS:000329186400019
PM 24385150
ER
PT J
AU Walkiewicz, MP
Dimitriadis, EK
Dalal, Y
AF Walkiewicz, Marcin P.
Dimitriadis, Emilios K.
Dalal, Yamini
TI CENP-A octamers do not confer a reduction in nucleosome height by AFM
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Letter
ID CENTROMERIC NUCLEOSOMES; HISTONE H3; IN-VITRO; KINETOCHORE; CHROMATIN;
RECONSTITUTION; MECHANISM
C1 [Walkiewicz, Marcin P.; Dalal, Yamini] NCI, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] Natl Inst BioImaging & BioEngn, NIH, Bethesda, MD USA.
RP Dalal, Y (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM dalaly@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011207-01, ZIA BC011207-03, ZIA BC011207-05,
ZIA BC011209-01, ZIA BC011209-03, ZIA BC011209-05, ZIA BC011209-06, ZIA
BC011207-02, ZIA BC011207-04, ZIA BC011207-06, ZIA BC011209-02, ZIA
BC011209-04]
NR 24
TC 12
Z9 12
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JAN
PY 2014
VL 21
IS 1
BP 2
EP 3
DI 10.1038/nsmb.2742
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 284BJ
UT WOS:000329290700002
PM 24389541
ER
PT J
AU Morris, SA
Baek, S
Sung, MH
John, S
Wiench, M
Johnson, TA
Schiltz, RL
Hager, GL
AF Morris, Stephanie A.
Baek, Songjoon
Sung, Myong-Hee
John, Sam
Wiench, Malgorzata
Johnson, Thomas A.
Schiltz, R. Louis
Hager, Gordon L.
TI Overlapping chromatin-remodeling systems collaborate genome wide at
dynamic chromatin transitions
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID GLUCOCORTICOID-RECEPTOR BINDING; MAMMALIAN SWI/SNF COMPLEXES; IN-VIVO;
DNA-SEQUENCE; PROMOTER NUCLEOSOMES; TRANSCRIPTION; ENZYMES; BRG1; ISWI;
ACCESSIBILITY
AB ATP-dependent chromatin remodeling is an essential process required for the dynamic organization of chromatin structure. Here we describe the genome-wide location and activity of three remodeler proteins with diverse physiological functions in the mouse genome: Brg1, Chd4 and Snf2h. The localization patterns of all three proteins substantially overlap with one another and with regions of accessible chromatin. Furthermore, using inducible mutant variants, we demonstrate that the catalytic activity of these proteins contributes to the remodeling of chromatin genome wide and that each of these remodelers can independently regulate chromatin reorganization at distinct sites. Many regions require the activity of more than one remodeler to regulate accessibility. These findings provide a dynamic view of chromatin organization and highlight the differential contributions of remodelers to chromatin maintenance in higher eukaryotes.
C1 [Morris, Stephanie A.; Baek, Songjoon; Sung, Myong-Hee; John, Sam; Wiench, Malgorzata; Johnson, Thomas A.; Schiltz, R. Louis; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM hagerg@exchange.nih.gov
FU Intramural Research Program of the US National Institutes of Health,
National Cancer Institute Center for Cancer Research; UNCF/Merck
Postdoctoral Science Research Fellowship
FX The authors thank D. Picketts (University of Ottawa) and J. Svaren
(University of Wisconsin) for the kind gift of remodeler cDNA constructs
(hSNF2H and mChd4, respectively), A. Indrawan for technical assistance,
the US National Cancer Institute Advanced Technology Program Sequencing
Facility for sequencing services and Epitomics, Inc. for generation of
the monoclonal rabbit antibody to BRG1. This research was supported by
the Intramural Research Program of the US National Institutes of Health,
National Cancer Institute Center for Cancer Research and by a UNCF/Merck
Postdoctoral Science Research Fellowship to S.A.M.
NR 62
TC 44
Z9 44
U1 5
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JAN
PY 2014
VL 21
IS 1
BP 73
EP +
DI 10.1038/nsmb.2718
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 284BJ
UT WOS:000329290700017
PM 24317492
ER
PT J
AU Kahn, J
Hayman, TJ
Jamal, M
Rath, BH
Kramp, T
Camphausen, K
Tofilon, PJ
AF Kahn, Jenna
Hayman, Thomas J.
Jamal, Muhammad
Rath, Barbara H.
Kramp, Tamalee
Camphausen, Kevin
Tofilon, Philip J.
TI The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of
glioblastoma stem-like cells
SO NEURO-ONCOLOGY
LA English
DT Article
DE AZD2014; glioblastoma; mTOR; orthotopic xenograft; Radiation; tumor stem
cell
ID TUMOR-INITIATING CELLS; TRANSLATION INITIATION; ANTITUMOR-ACTIVITY;
IONIZING IRRADIATION; DNA-DAMAGE; FACTOR 4E; IN-VITRO; CANCER; MTOR;
RAPAMYCIN
AB The mammalian target of rapamycin (mTOR) has been suggested as a target for radiosensitization. Given that radiotherapy is a primary treatment modality for glioblastoma (GBM) and that mTOR is often dysregulated in GBM, the goal of this study was to determine the effects of AZD2014, a dual mTORC1/2 inhibitor, on the radiosensitivity of GBM stem-like cells (GSCs).
mTORC1 and mTORC2 activities were defined by immunoblot analysis. The effects of this mTOR inhibitor on the in vitro radiosensitivity of GSCs were determined using a clonogenic assay. DNA double strand breaks were evaluated according to H2AX foci. Orthotopic xenografts initiated from GSCs were used to define the in vivo response to AZD2014 and radiation.
Exposure of GSCs to AZD2014 resulted in the inhibition of mTORC1 and 2 activities. Based on clonogenic survival analysis, addition of AZD2014 to culture media 1 hour before irradiation enhanced the radiosensitivity of CD133 and CD15 GSC cell lines. Whereas AZD2014 treatment had no effect on the initial level of H2AX foci, the dispersal of radiation-induced H2AX foci was significantly delayed. Finally, the combination of AZD2014 and radiation delivered to mice bearing GSC-initiated orthotopic xenografts significantly prolonged survival as compared with the individual treatments.
These data indicate that AZD2014 enhances the radiosensitivity of GSCs both in vitro and under orthotopic in vivo conditions and suggest that this effect involves an inhibition of DNA repair. Moreover, these results suggest that this dual mTORC1/2 inhibitor may be a radiosensitizer applicable to GBM therapy.
C1 [Kahn, Jenna; Hayman, Thomas J.; Jamal, Muhammad; Rath, Barbara H.; Kramp, Tamalee; Camphausen, Kevin; Tofilon, Philip J.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kahn, Jenna] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA.
[Hayman, Thomas J.] Univ S Florida, Morsani Coll Med, Tampa, FL USA.
RP Tofilon, PJ (reprint author), NCI, 10 Ctr Dr MSC 1002,Bldg 10,B3B69B, Bethesda, MD 20892 USA.
EM tofilonp@mail.nih.gov
FU Division of Basic Sciences, National Cancer Institute [Z1A BC011372, Z1A
BC011373]
FX Division of Basic Sciences, National Cancer Institute (Z1A BC011372, Z1A
BC011373).
NR 44
TC 19
Z9 21
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JAN
PY 2014
VL 16
IS 1
BP 29
EP 37
DI 10.1093/neuonc/not139
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 281YC
UT WOS:000329135900006
PM 24311635
ER
PT J
AU He, MG
Abdou, A
Ellwein, LB
Naidoo, KS
Sapkota, YD
Thulasiraj, RD
Varma, R
Zhao, JL
Kocur, I
Congdon, NG
AF He, Mingguang
Abdou, Amza
Ellwein, Leon B.
Naidoo, Kovin S.
Sapkota, Yuddha D.
Thulasiraj, R. D.
Varma, Rohit
Zhao, Jialiang
Kocur, Ivo
Congdon, Nathan G.
TI Age-related Prevalence and Met Need for Correctable and Uncorrectable
Near Vision Impairment in a Multi-country Study
SO OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; FUNCTIONAL PRESBYOPIA; POPULATION; INDIA; EYE
AB Purpose: To estimate the prevalence, potential determinants, and proportion of met need for near vision impairment (NVI) correctable with refraction approximately 2 years after initial examination of a multi-country cohort.
Design: Population-based, prospective cohort study.
Participants: People aged 35 years examined at baseline in semi-rural (Shunyi) and urban (Guangzhou) sites in China; rural sites in Nepal (Kaski), India (Madurai), and Niger (Dosso); a semi-urban site (Durban) in South Africa; and an urban site (Los Angeles) in the United States. Methods: Near visual acuity (NVA) with and without current near correction was measured at 40 cm using a logarithm of the minimum angle of resolution near vision tumbling E chart. Participants with uncorrected binocular NVA 20/ 40 were tested with plus sphere lenses to obtain best-corrected binocular NVA. Main Outcome Measures: Prevalence of total NVI (defined as uncorrected NVA 20/ 40) and NVI correctable and uncorrectable to > 20/ 40, and current spectacle wearing among those with bilateral NVA 20/ 63 improving to > 20/ 40 with near correction (met need).
Results: Among 13 671 baseline participants, 10 533 (77.2%) attended the follow-up examination. The prevalence of correctable NVI increased with age from 35 to 50e60 years and then decreased at all sites. Multiple logistic regression modeling suggested that correctable NVI was not associated with gender at any site, whereas more educated persons aged > 54 years were associated with a higher prevalence of correctable NVI in Nepal and India. Although near vision spectacles were provided free at baseline, wear among those who could benefit was < 40% at all but 2 centers (Guangzhou and Los Angeles).
Conclusions: Prevalence of correctable NVI is greatest among persons of working age, and rates of correction are low in many settings, suggesting that strategies targeting the workplace may be needed. Ophthalmology 2014; 121: 417-422 (C) 2014 by the American Academy of Ophthalmology.
C1 [He, Mingguang; Congdon, Nathan G.] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
[Abdou, Amza] Minist Sante Publ, Programme Natl Lutte Cecite, Niamey, Niger.
[Ellwein, Leon B.] NEI, Bethesda, MD 20892 USA.
[Naidoo, Kovin S.] Univ KwaZulu Natal, Brien Holden Vis Inst, Durban, South Africa.
[Naidoo, Kovin S.] Univ KwaZulu Natal, AVRI, Durban, South Africa.
[Sapkota, Yuddha D.] Nepal Netra Jyoti Sangh, Kathmandu, Nepal.
[Thulasiraj, R. D.] Aravind Eye Care Syst, Lions Aravind Inst Community Ophthalmol, Madurai, Tamil Nadu, India.
[Varma, Rohit] Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA.
[Zhao, Jialiang] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
[Zhao, Jialiang] Beijing Union Med Coll Hosp, Beijing, Peoples R China.
[Kocur, Ivo] WHO, CH-1211 Geneva, Switzerland.
[Congdon, Nathan G.] ORBIS Int, New York, NY USA.
RP He, MG (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab, 54 Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM mingguang_he@yahoo.com
FU World Health Organization, Geneva, Switzerland [N01-EY-2103)]
FX Funding: Supported by the World Health Organization, Geneva, Switzerland
(under National Institutes of Health, Bethesda, MD, contract No.
N01-EY-2103).
NR 14
TC 2
Z9 2
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JAN
PY 2014
VL 121
IS 1
BP 417
EP 422
DI 10.1016/j.ophtha.2013.06.051
PG 6
WC Ophthalmology
SC Ophthalmology
GA 282KG
UT WOS:000329169500064
PM 23993359
ER
PT J
AU Ramos-Alvarez, I
Moreno-Villegas, Z
Martin-Duce, A
Sanz, R
Aparicio, C
Portal-Nunez, S
Mantey, SA
Jensen, RT
Gonzalez, N
AF Ramos-Alvarez, I.
Moreno-Villegas, Z.
Martin-Duce, A.
Sanz, R.
Aparicio, C.
Portal-Nunez, S.
Mantey, S. A.
Jensen, R. T.
Gonzalez, N.
TI Human BRS-3 receptor: Functions/role in cell signaling pathways and
glucose metabolism in obese or diabetic myocytes
SO PEPTIDES
LA English
DT Article
DE BRS-3 human muscle; Signaling; Glucose metabolism; Diabetes; Obesity
ID GASTRIN-RELEASING-PEPTIDE; MAMMALIAN BOMBESIN RECEPTORS; HUMAN ORPHAN
RECEPTOR; LUNG-CANCER CELLS; SUBTYPE-3 BRS-3; SUBTYPE-3-DEFICIENT MICE;
SKELETAL-MUSCLE; MOLECULAR-BASIS; AGONIST; RAT
AB Several studies showed that the orphan Bombesin Receptor Subtype-3 (BRS-3) - member of the bombesin receptor family - has an important role in glucose homeostasis (v.g.: BRS-3-KO mice developed mild obesity, and decreased levels of BRS-3 mRNA/protein have been described in muscle from obese ( OB) and type 2 diabetic (T2D) patients). In this work, to gain insight into BRS-3 receptor cell signaling pathways, and its implication on glucose metabolism, primary cultured myocytes from normal subjects, OB or T2D patients were tested using high affinity ligand - [D-Tyr(6),beta-Ala(11),Phe(13),Nle(14)]bombesin(6-14). In muscle cells from all metabolic conditions, the compound significantly increased not only MAPKs, p90RSK1, PKB and p7056K phosphorylation levels, but also PI3K activity; moreover, it produced a dose-response stimulation of glycogen synthase a activity and glycogen synthesis. Myocytes from OB and T2D patients were more sensitive to the ligand than normal, and T2D cells even more than obese myocytes. These results widen the knowledge of human BRS-3 cell signaling pathways induced by a BRS-3 agonist, described its insulin-mimetic effects on glucose metabolism, showed the role of BRS-3 receptor in glucose homeostasis, and also propose the employing of BRS-3/ligand system, as participant in the obese and diabetic therapies. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Ramos-Alvarez, I.; Moreno-Villegas, Z.; Gonzalez, N.] CIBERDEM, IIS Fdn Jimenez Diaz, Dept Metab Nutr & Hormones, Madrid, Spain.
[Martin-Duce, A.] Univ Alcala de Henares, Surg Unit, Dept Nursery, Madrid, Spain.
[Sanz, R.] IIS Fdn Jimenez Diaz, Dept Neurol, Madrid 28040, Spain.
[Aparicio, C.] Fdn Jimenez Diaz, Dept Vasc Surg, Madrid, Spain.
[Portal-Nunez, S.] IIS Fdn Jimenez Diaz, Dept Bone Mineral Metab, Madrid 28040, Spain.
[Mantey, S. A.; Jensen, R. T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, N (reprint author), IIS Fdn Jimenez Diaz, Dpt Metab Nutr & Hormonas, Avda Reyes Catolicos 2, Madrid 28040, Spain.
EM ngonzalezg@fjd.es
RI Portal-Nunez, Sergio/L-7391-2014; Gonzalez, Nieves/N-2199-2014
OI Portal-Nunez, Sergio/0000-0003-0659-1545; Gonzalez,
Nieves/0000-0002-1551-2872
FU Institute of Health Carlos III [CP08/00158]; Fundacion Rodriguez
Pascual, Spain
FX This study was supported by a grant from the Institute of Health Carlos
III (CP08/00158) and Fundacion Rodriguez Pascual, Spain. IRA was
Research Fellow from the Fundacion Conchita Rabago de Jimenez Diaz.
NR 36
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
EI 1873-5169
J9 PEPTIDES
JI Peptides
PD JAN
PY 2014
VL 51
BP 91
EP 99
DI 10.1016/j.peptides.2013.11.002
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 282XO
UT WOS:000329208100015
PM 24220502
ER
PT J
AU Zhou, YJ
Boudreau, DM
Freedman, AN
AF Zhou, Yingjun
Boudreau, Denise M.
Freedman, Andrew N.
TI Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in
the general US population
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE aspirin; NSAIDs; NHIS; prevalence; pharmacoepidemiology
ID SERVICES-TASK-FORCE; RANDOMIZED CONTROLLED-TRIALS;
COLLEGE-OF-CARDIOLOGY; LUNG-CANCER RISK; COLORECTAL-CANCER;
CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; PANCREATIC-CANCER; REGULAR
ASPIRIN; CYCLOOXYGENASE-2 INHIBITORS
AB PurposeThe objective of this study was to describe trends in the prevalence of regular aspirin and nonsteroidal anti-inflammatory drug (NSAID) use among adults in the United States during 2005 and 2010, and to identify characteristics of regular users.
MethodsData from the 2005 and 2010 National Health Interview Survey (NHIS) were analyzed to estimate the prevalence of regular use of aspirin and NSAIDs among U.S. adults aged 18years and older. Results were stratified by demographics and self-reported medical conditions and extrapolated to provide U.S. population estimates.
ResultsIn 2010, around 43 million adults (19.0%) took aspirin at least three times per week for more than 3months (i.e. regular users), and more than 29 million adults (12.1%) were regular users of NSAIDs. Compared with 2005, this was an overall increase of 57% in aspirin use and 41% in NSAID use. These increases were consistent across the strata of age, sex, race, and selected medical conditions, including cardiovascular disease (CVD), arthritis, peptic ulcers, cancer, and severe headache, except for Asian Americans.
ConclusionLarge increases in the use of both aspirin and NSAIDs were observed over a 5year period. The increase may be the result of increasing media attention reporting that regular aspirin use lowers the risk of CVD and related deaths, and may also prevent cancer. Moreover, safety concerns related to alternative medications such as acetaminophen and selective COX-2 inhibitors may influence users of these drugs to switch to aspirin and NSAIDs. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Zhou, Yingjun; Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Boudreau, Denise M.] Grp Hlth Res Inst, Seattle, WA USA.
[Boudreau, Denise M.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
RP Freedman, AN (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 5128, Bethesda, MD 20892 USA.
EM Andrew_Freedman@nih.gov
NR 62
TC 45
Z9 46
U1 6
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD JAN
PY 2014
VL 23
IS 1
BP 43
EP 50
DI 10.1002/pds.3463
PG 8
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 282ND
UT WOS:000329177700007
PM 23723142
ER
PT J
AU Simpson, RM
Bastian, BC
Michael, HT
Webster, JD
Prasad, ML
Conway, CM
Prieto, VM
Gary, JM
Goldschmidt, MH
Esplin, DG
Smedley, RC
Piris, A
Meuten, DJ
Kiupel, M
Lee, CCR
Ward, JM
Dwyer, JE
Davis, BJ
Anver, MR
Molinolo, AA
Hoover, SB
Rodriguez-Canales, J
Hewitt, SM
AF Simpson, R. Mark
Bastian, Boris C.
Michael, Helen T.
Webster, Joshua D.
Prasad, Manju L.
Conway, Catherine M.
Prieto, Victor M.
Gary, Joy M.
Goldschmidt, Michael H.
Esplin, D. Glen
Smedley, Rebecca C.
Piris, Adriano
Meuten, Donald J.
Kiupel, Matti
Lee, Chyi-Chia R.
Ward, Jerrold M.
Dwyer, Jennifer E.
Davis, Barbara J.
Anver, Miriam R.
Molinolo, Alfredo A.
Hoover, Shelley B.
Rodriguez-Canales, Jaime
Hewitt, Stephen M.
TI Sporadic naturally occurring melanoma in dogs as a preclinical model for
human melanoma
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE melanoma; animal model; comparative study; clinical trial design; image
analysis; digital telepathology; signal transduction
ID ORAL MALIGNANT MELANOMAS; MUCOSAL MELANOMA; MELANOCYTIC NEOPLASMS;
METASTATIC MELANOMA; DISTINCT SUBTYPES; CLINICAL-EFFICACY; BRAF
MUTATIONS; ACTIVATED AKT; CELL-LINES; KIT
AB Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model.
C1 [Simpson, R. Mark; Michael, Helen T.; Webster, Joshua D.; Gary, Joy M.; Dwyer, Jennifer E.; Hoover, Shelley B.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Bastian, Boris C.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Bastian, Boris C.] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Prasad, Manju L.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Conway, Catherine M.; Lee, Chyi-Chia R.; Rodriguez-Canales, Jaime; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Prieto, Victor M.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Prieto, Victor M.] Univ Texas MD Anderson Canc Ctr, Dept Dermatol, Houston, TX 77030 USA.
[Goldschmidt, Michael H.] Univ Penn, Sch Vet Med, Lab Pathol & Toxicol, Philadelphia, PA 19104 USA.
[Esplin, D. Glen] ARUP Labs, Anim Reference Pathol Div, Salt Lake City, UT USA.
[Smedley, Rebecca C.; Kiupel, Matti] Michigan State Univ, Diagnost Ctr Populat & Anim Hlth, E Lansing, MI 48824 USA.
[Piris, Adriano] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA.
[Piris, Adriano] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Meuten, Donald J.] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA.
[Kiupel, Matti] Michigan State Univ, Dept Pathobiol & Diagnost Invest, Lansing, MI USA.
[Ward, Jerrold M.] Global Vet Pathol Inc, Montgomery Village, MD USA.
[Ward, Jerrold M.] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, Bethesda, MD 20892 USA.
[Davis, Barbara J.] Davis Toxicol Pathol Consulting, Harvard, MA USA.
[Anver, Miriam R.] Sci Applicat Int Corp Frederick Inc, Pathol Histotechnol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Molinolo, Alfredo A.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA.
RP Simpson, RM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
EM ms43b@nih.gov; genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Goldschmidt,
Michael/0000-0001-9515-0535
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; [R01- CA131524]; [P01 CA025874]
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Additional funding support was provided by The Animal Cancer Foundation,
Norwalk, Connecticut [www.acfoundation.org/], and The Canine Comparative
Oncology and Genomics Consortium, Inc., Rockville, Maryland
[http://www.ccogc.net/]. NCI Comparative Melanoma Tumor Board meeting
support was provided by the NCI Center for Cancer Research and The
Animal Cancer Foundation. Dr. B. C. Bastian is supported by awards R01-
CA131524, and P01 CA025874. Drs. J. M. Gary and H. T. Michael are
currently molecular pathology fellows in the NIH Comparative Biomedical
Scientist Training Program supported by the National Cancer Institute,
in partnership with Michigan State University, East Lansing (Gary) and
University of Maryland, College Park (Michael). Dr. M. R. Anver receives
support through the National Cancer Institute, National Institutes of
Health, under Contract No. HHSN261200800001E. The authors thank
Christina Mazcko, NCI, for assistance with study specimens and patient
data, and John Hickerson, Kelly Government Solutions, for logistical
support of tumor board study meetings. The views of the authors and
tumor board members are their own, and no commercial endorsement is
attributable to them or their affiliations.
NR 55
TC 21
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U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD JAN
PY 2014
VL 27
IS 1
DI 10.1111/pcmr.12185
PG 12
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 274UG
UT WOS:000328631100010
PM 24128326
ER
PT J
AU Zhang, YL
Helke, KL
Coelho, SG
Valencia, JC
Hearing, VJ
Sun, SL
Liu, B
Li, ZH
AF Zhang, Yongliang
Helke, Kristi L.
Coelho, Sergio G.
Valencia, Julio C.
Hearing, Vincent J.
Sun, Shaoli
Liu, Bei
Li, Zihai
TI Essential role of the molecular chaperone gp96 in regulating
melanogenesis
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE Gp96; melanogenesis; tyrosinase; melanosome
ID SHOCK-PROTEIN GP96; B16 MELANOMA-CELLS; ENDOPLASMIC-RETICULUM;
OCULOCUTANEOUS ALBINISM; QUALITY-CONTROL; MOUSE MELANOMA; TYROSINASE;
MELANOCYTES; INHIBITION; MELANOSOMES
AB Through a process known as melanogenesis, melanocyte produces melanin in specialized organelles termed melanosomes, which regulates pigmentation of the skin, eyes, and hair. Gp96 is a constitutively expressed heat shock protein in the endoplasmic reticulum whose expression is further upregulated upon ultraviolet irradiation. However, the roles and mechanisms of this chaperone in pigmentation biology are unknown. In this study, we found that knockdown of gp96 by RNA interference significantly perturbed melanin synthesis and blocked late melanosome maturation. Gp96 knockdown did not impair the expression of tyrosinase, an essential enzyme in melanin synthesis, but compromised its catalytic activity and melanosome translocation. Further, mice with melanocyte-specific deletion of gp96 displayed decreased pigmentation. A mechanistic study revealed that the defect in melanogenesis can be rescued by activation of the canonical Wnt pathway, consistent with the critical roles of gp96 in chaperoning Wnt-coreceptor LRP6. Thus, this work uncovered the essential role of gp96 in regulating melanogenesis.
C1 [Zhang, Yongliang; Liu, Bei; Li, Zihai] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
[Helke, Kristi L.] Med Univ S Carolina, Dept Comparat Med, Charleston, SC 29425 USA.
[Helke, Kristi L.; Sun, Shaoli] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
[Coelho, Sergio G.; Valencia, Julio C.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, ZH (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA.
EM zihai@musc.edu
RI zhang, yongliang/N-8326-2013;
OI Helke, Kris/0000-0001-9746-0764
FU Intramural Research Program of the National Cancer Institute at NIH; NIH
extramural Grants [AI070603, AI077283]
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute at NIH (to V.H.) and by NIH extramural
Grants AI070603 and AI077283 to Z.L.
NR 38
TC 3
Z9 3
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD JAN
PY 2014
VL 27
IS 1
DI 10.1111/pcmr.12165
PG 9
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 274UG
UT WOS:000328631100014
PM 24024552
ER
PT J
AU Phillips, SM
McAuley, E
AF Phillips, Siobhan M.
McAuley, Edward
TI Physical activity and quality of life in breast cancer survivors: the
role of self-efficacy and health status
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE breast cancer survivors; physical activity; quality of life;
self-efficacy; health status
ID MAXIMUM-LIKELIHOOD-ESTIMATION; STRUCTURAL EQUATION MODELS; OLDER-ADULTS;
CLINICAL-TRIALS; MISSING DATA; METAANALYSIS; EXERCISE; PARTICIPATION;
POPULATION; THERAPY
AB ObjectiveMechanisms underlying the relationship between physical activity and quality of life (QOL) in breast cancer survivors are not well understood. The purpose of the present study was to longitudinally test a model examining self-efficacy and health status as potential mediators of this relationship.
MethodsAt baseline and 6months, breast cancer survivors (n=1527) completed physical activity, self-efficacy, health status, and QOL measures, and a subsample (n=370) wore an accelerometer. Panel analysis within a covariance modeling framework was used to test the hypothesis that physical activity indirectly influences QOL across time.
ResultsThe hypothesized model provided a good fit in the full sample ((2)=409.06; d.f.=91, p<0.001; comparative fit index (CFI)=0.98; standardized root mean residual (SRMR)=0.04) and the accelerometer subsample ((2)=320.96, d.f.=134, p<0.001; CFI=0.95; SRMR=0.05), indicating that physical activity indirectly, via self-efficacy and health status indicators, influences QOL across time.
ConclusionsPhysical activity may influence QOL in breast cancer survivors through more proximal, modifiable factors. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Phillips, Siobhan M.; McAuley, Edward] Univ Illinois, Dept Kinesiol & Community Hlth, Urbana, IL USA.
RP Phillips, SM (reprint author), NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, 9609 Med Ctr Dr,Off 4E516, Rockville, MD 20850 USA.
EM siobhan.phillips@mail.nih.gov
FU National Institute on Aging at the National Institutes of Health
[F31AG034025, AG020118]; Shahid and Ann Carlson Khan endowed
professorship
FX This work was supported by the National Institute on Aging at the
National Institutes of Health through award numbers F31AG034025 and
AG020118, and the Shahid and Ann Carlson Khan endowed professorship.
NR 43
TC 7
Z9 7
U1 2
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JAN
PY 2014
VL 23
IS 1
BP 27
EP 34
DI 10.1002/pon.3366
PG 8
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 281ZW
UT WOS:000329140800004
PM 24003002
ER
PT J
AU Fu, Y
Mi, LX
Sanda, M
Silverstein, S
Aggarwal, M
Wang, DY
Gupta, P
Goldman, R
Appella, DH
Chung, FL
AF Fu, Ying
Mi, Lixin
Sanda, Miloslav
Silverstein, Shana
Aggarwal, Monika
Wang, Deyun
Gupta, Pankaj
Goldman, Radoslav
Appella, Daniel H.
Chung, Fung-Lung
TI A click chemistry approach to identify protein targets of cancer
chemopreventive phenethyl isothiocyanate
SO RSC ADVANCES
LA English
DT Article
ID APOPTOSIS; IDENTIFICATION; SULFORAPHANE; BINDING; CELLS; PROTEOMICS;
MECHANISM; PRODUCTS; PLASMA; ARREST
AB Here we report the identification of protein targets of chemopreventive phenethyl isothiocyanate (PEITC) via "click" chemistry in the A549 human lung cancer cell line, using a novel alkyne-tagged PEITC which was also found to show potent in vitro anticancer activity.
C1 [Fu, Ying; Mi, Lixin; Sanda, Miloslav; Silverstein, Shana; Aggarwal, Monika; Goldman, Radoslav; Chung, Fung-Lung] Georgetown Univ, Lombardi Canc Res Ctr, Washington, DC 20007 USA.
[Wang, Deyun; Gupta, Pankaj; Appella, Daniel H.] NIDDK, NIH, Bethesda, MD 20814 USA.
RP Chung, FL (reprint author), Georgetown Univ, Lombardi Canc Res Ctr, Washington, DC 20007 USA.
EM appellad@niddk.nih.gov; flc6@georgetown.edu
FU NCI [CA100853, RO1-CA-100083-7]; National Institutes of Health
[RO1CA135069]; Lombardi Cancer Center [P30 CA51008]
FX This work is supported by NCI (grant CA100853 and RO1-CA-100083-7),
National Institutes of Health grant RO1CA135069 and Lombardi Cancer
Center Support Grant P30 CA51008. We thank Dr Lawrence Marnett
(Vanderbilt University) and Dr Qiang Zhang (University of Warwick) for
the suggestions on "click" chemistry, Mr Jishen Pan and Dr Marcin Dyba
for the help of HPLC purification, Drs Ercheng Li, Amrita Cheema and
Georgetown Lombardi Shared Resources for NMR and MS analysis, Dr Karen
Creswell and Ms Marcy Chen (both are from core facilities of Lombardi
Comprehensive Cancer Centre at Georgetown University) for flow cytometry
analysis.
NR 25
TC 1
Z9 1
U1 1
U2 13
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2046-2069
J9 RSC ADV
JI RSC Adv.
PY 2014
VL 4
IS 8
BP 3920
EP 3923
DI 10.1039/c3ra46849f
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 280ON
UT WOS:000329040500032
ER
PT J
AU Aagaard, KM
Segars, JH
AF Aagaard, Kjersti M.
Segars, James H.
TI What Is the Microbiome and How Do We Study It? Preface
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Editorial Material
C1 [Aagaard, Kjersti M.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Aagaard, KM (reprint author), HGSC, Dept Obstet & Gynecol, Div Maternal Fetal Med, 1 Baylor Plaza, Houston, TX 77030 USA.
EM aagaardt@bcm.edu
FU Intramural NIH HHS [ZIE HD008737-13]; NIDDK NIH HHS [P30 DK056338]
NR 0
TC 1
Z9 1
U1 2
U2 8
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JAN
PY 2014
VL 32
IS 1
BP 3
EP 4
DI 10.1055/s-0033-1361816
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 285AQ
UT WOS:000329365200002
PM 24390914
ER
PT J
AU Sirota, I
Zarek, SM
Segars, JH
AF Sirota, Ido
Zarek, Shvetha M.
Segars, James H.
TI Potential Influence of the Microbiome on Infertility and Assisted
Reproductive Technology
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE microbiome; in vitro fertilization; Lactobacillus; progesterone
ID IN-VITRO FERTILIZATION; COLONY-STIMULATING FACTOR; UTERINE
EPITHELIAL-CELLS; CULTIVATION-INDEPENDENT METHODS; GRADIENT
GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; BACTERIAL VAGINOSIS;
HUMAN-ENDOMETRIUM; EMBRYO-TRANSFER; PROGESTERONE RESISTANCE
AB Although an altered vaginal microbiota has been demonstrated to affect parturition, its role in assisted reproductive technologies is uncertain. Nevertheless, the effect of known pathogens such as Mycoplasma tuberculosis, Chlamydia trachomatis, and Neisseria gonorrhoeae is clear, causing subclinical changes thought to be risk factors in subfertility. The Human Microbiome Project (HMP) has allowed for metagenomic studies to aid in characterizing normal vaginal flora. Recent findings from the HMP demonstrate that many different species of Lactobacillus are present in the vaginal tract, with a few that predominate. Studies that characterize the vaginal microbiome in assisted reproductive technology support the hypothesis that colonizing the transfer-catheter tip with Lactobacillus crispatus at the time of embryo transfer may increase the rates of implantation and live birth rate while decreasing the rate of infection. In addition, there is some evidence that a progesterone-resistant endometrium might increase the risk of an abnormal vaginal microbiome.
C1 [Sirota, Ido] St Lukes Roosevelt Hosp, Dept Obstet & Gynecol, New York, NY USA.
[Zarek, Shvetha M.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 CRC Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU Intramural research program of the Program in Reproductive and Adult
Endocrinology, NICHD, NIH
FX This research was supported, in part, by Intramural research program of
the Program in Reproductive and Adult Endocrinology, NICHD, NIH.
NR 106
TC 9
Z9 10
U1 3
U2 25
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JAN
PY 2014
VL 32
IS 1
BP 35
EP 42
DI 10.1055/s-0033-1361821
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 285AQ
UT WOS:000329365200007
PM 24390919
ER
PT J
AU Sharma, H
Tal, R
Clark, NA
Segars, JH
AF Sharma, Harsha
Tal, Reshef
Clark, Natalie A.
Segars, James H.
TI Microbiota and Pelvic Inflammatory Disease
SO SEMINARS IN REPRODUCTIVE MEDICINE
LA English
DT Article
DE vaginal microbiota; bacterial vaginosis; pelvic inflammatory disease
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHLAMYDIA-TRACHOMATIS INFECTION;
REPRODUCTIVE-AGE WOMEN; FEMALE GENITAL-TRACT; VAGINAL BACTERIAL
COMMUNITIES; TUBO-OVARIAN ABSCESS; TRICHOMONAS-VAGINALIS;
MYCOPLASMA-GENITALIUM; TUBOOVARIAN ABSCESS; ATOPOBIUM-VAGINAE
AB Female genital tract microbiota play a crucial role in maintaining health. Disequilibrium of the microbiota has been associated with increased risk of pelvic infections. In recent years, culture-independent molecular techniques have expanded understanding of the composition of genital microbiota and the dynamic nature of the microbiota. There is evidence that upper genital tract may not be sterile and may harbor microflora in the physiologic state. The isolation of bacterial vaginosis-associated organisms in women with genital infections establishes a link between pelvic infections and abnormal vaginal flora. With the understanding of the composition of the microbiota in healthy and diseased states, the next logical step is to identify the function of the newly identified microbes. This knowledge will further expand our understanding of the causation of pelvic infections, which may lead to more effective prevention and treatment strategies.
C1 [Sharma, Harsha] Queens Hosp Ctr, Mt Sinai Sch Med, Jamaica Program, Dept Obstet & Gynecol, Queens, NY USA.
[Tal, Reshef] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
[Clark, Natalie A.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Segars, JH (reprint author), NIH, CRC, Bldg 10,Room 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
OI Tal, Reshef/0000-0002-2500-9904
FU NIH Intramural Research Program in Reproductive and Adult Endocrinology
FX This research was supported in part by the NIH Intramural Research
Program in Reproductive and Adult Endocrinology.
NR 102
TC 12
Z9 14
U1 3
U2 13
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 1526-8004
EI 1526-4564
J9 SEMIN REPROD MED
JI Semin. Reprod. Med.
PD JAN
PY 2014
VL 32
IS 1
BP 43
EP 49
DI 10.1055/s-0033-1361822
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 285AQ
UT WOS:000329365200008
PM 24390920
ER
PT S
AU Domagalski, MJ
Zheng, HP
Zimmerman, MD
Dauter, Z
Wlodawer, A
Minor, W
AF Domagalski, Marcin J.
Zheng, Heping
Zimmerman, Matthew D.
Dauter, Zbigniew
Wlodawer, Alexander
Minor, Wladek
BE Chen, YW
TI The Quality and Validation of Structures from Structural Genomics
SO STRUCTURAL GENOMICS: GENERAL APPLICATIONS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Structure quality; Structure validation; Drug discovery; Data mining;
Structural genomics
ID PROTEIN DATA-BANK; CRYSTAL-STRUCTURES; WATER-MOLECULES; STRUCTURE
REFINEMENT; DENSITY MODIFICATION; MODEL; CRYSTALLOGRAPHY; REPLACEMENT;
DIFFRACTION; RESOLUTION
AB Quality control of three-dimensional structures of macromolecules is a critical step to ensure the integrity of structural biology data, especially those produced by structural genomics centers. Whereas the Protein Data Bank (PDB) has proven to be a remarkable success overall, the inconsistent quality of structures reveals a lack of universal standards for structure/deposit validation. Here, we review the state-of-the-art methods used in macromolecular structure validation, focusing on validation of structures determined by X-ray crystallography. We describe some general protocols used in the rebuilding and re-refinement of problematic structural models. We also briefly discuss some frontier areas of structure validation, including refinement of protein-ligand complexes, automation of structure redetermination, and the use of NMR structures and computational models to solve X-ray crystal structures by molecular replacement.
C1 [Domagalski, Marcin J.; Zheng, Heping; Zimmerman, Matthew D.; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22903 USA.
[Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Argonne Natl Lab, Argonne, IL USA.
[Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21701 USA.
RP Domagalski, MJ (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22903 USA.
RI Minor, Wladek/F-3096-2014; Zimmerman, Matthew/N-9489-2013;
OI Zimmerman, Matthew/0000-0002-6274-9493; Minor,
Wladek/0000-0001-7075-7090
FU Intramural NIH HHS; NCI NIH HHS [P30 CA044579]; NIAID NIH HHS
[HHSN272201200026C]; NIGMS NIH HHS [R01 GM053163, U54 GM094585, U54
GM094662]; PHS HHS [HHSN272201200026C]
NR 42
TC 6
Z9 6
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 978-1-62703-691-7; 978-1-62703-690-0
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1091
BP 297
EP 314
DI 10.1007/978-1-62703-691-7_21
D2 10.1007/978-1-62703-691-7
PG 18
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics
& Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA BJJ06
UT WOS:000328383200022
PM 24203341
ER
PT J
AU Beratarrechea, A
Lee, AG
Willner, JM
Jahangir, E
Ciapponi, A
Rubinstein, A
AF Beratarrechea, Andrea
Lee, Allison G.
Willner, Jonathan M.
Jahangir, Eiman
Ciapponi, Agustin
Rubinstein, Adolfo
TI The Impact of Mobile Health Interventions on Chronic Disease Outcomes in
Developing Countries: A Systematic Review
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE chronic disease; mobile health; short message service; cellular phone;
developing countries; systematic review
ID RANDOMIZED CONTROLLED-TRIAL; SHORT-MESSAGE SERVICE; IMPROVE ATTENDANCE;
BEHAVIOR-CHANGE; ASTHMA CONTROL; CARE; TELEPHONE; REMINDERS; MANAGEMENT;
PHONES
AB Introduction:Rates of chronic diseases will continue to rise in developing countries unless effective and cost-effective interventions are implemented. This review aims to discuss the impact of mobile health (m-health) on chronic disease outcomes in low- and middle-income countries (LMIC).Materials and Methods:Systematic literature searches were performed using CENTRAL, MEDLINE, EMBASE, and LILACS databases and gray literature. Scientific literature was searched to identify controlled studies evaluating cell phone voice and text message interventions to address chronic diseases in adults in low- or middle-income countries. Outcomes measured included morbidity, mortality, hospitalization rates, behavioral or lifestyle changes, process of care improvements, clinical outcomes, costs, patient-provider satisfaction, compliance, and health-related quality of life (HRQoL).Results:From the 1,709 abstracts retrieved, 163 articles were selected for full text review, including 9 randomized controlled trials with 4,604 participants. Most of the studies addressed more than one outcome. Of the articles selected, six studied clinical outcomes, six studied processes of care, three examined healthcare costs, and two examined HRQoL. M-health positively impacted on chronic disease outcomes, improving attendance rates, clinical outcomes, and HRQoL, and was cost-effective.Conclusions:M-health is emerging as a promising tool to address access, coverage, and equity gaps in developing countries and low-resource settings. The results for m-health interventions showed a positive impact on chronic diseases in LMIC. However, a limiting factor of this review was the relatively small number of studies and patients enrolled, highlighting the need for more rigorous research in this area in developing countries.
C1 [Beratarrechea, Andrea; Ciapponi, Agustin; Rubinstein, Adolfo] South Amer Ctr Excellence Cardiovasc Hlth, Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Lee, Allison G.; Willner, Jonathan M.; Jahangir, Eiman] Fogarty Int Ctr, Bethesda, MD USA.
RP Beratarrechea, A (reprint author), South Amer Ctr Excellence Cardiovasc Hlth, Inst Clin Effectiveness & Hlth Policy, Emilio Ravignani 2024,C1414CPV, Buenos Aires, DF, Argentina.
EM aberatarrechea@iecs.org.ar
RI Jahangir, Eiman/P-1053-2015; Emchi, Karma/Q-1952-2016
OI Jahangir, Eiman/0000-0001-6944-5321;
FU National Institutes of Health; Office of the Director; Fogarty
International Center; Office of AIDS Research; National Cancer Center;
National Eye Institute; National Heart, Blood, and Lung Institute;
National Institute of Dental and Craniofacial Research; National
Institute on Drug Abuse; National Institute of Mental Health; National
Institute of Allergy and Infectious Diseases; National Institutes of
Health Office of Women's Health and Research through the Vanderbilt
University [R24 TW007988]; American Relief and Recovery Act
FX A.G.L., J.M.W., and E.J. received funding as a Fogarty International
Clinical Research Fellow, a program that is supported by the National
Institutes of Health, Office of the Director, Fogarty International
Center, Office of AIDS Research, National Cancer Center, National Eye
Institute, National Heart, Blood, and Lung Institute, National Institute
of Dental and Craniofacial Research, National Institute on Drug Abuse,
National Institute of Mental Health, National Institute of Allergy and
Infectious Diseases, and National Institutes of Health Office of Women's
Health and Research through the International Clinical Research Scholars
and Fellows Program at Vanderbilt University (R24 TW007988) and the
American Relief and Recovery Act.
NR 52
TC 48
Z9 49
U1 1
U2 33
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD JAN 1
PY 2014
VL 20
IS 1
BP 75
EP 82
DI 10.1089/tmj.2012.0328
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 282HV
UT WOS:000329162700011
PM 24205809
ER
PT J
AU Ward, JM
Rehg, JE
AF Ward, J. M.
Rehg, J. E.
TI Rodent Immunohistochemistry: Pitfalls and Troubleshooting
SO VETERINARY PATHOLOGY
LA English
DT Article
DE immunohistochemistry; IHC; antibodies; background staining; artifacts;
mice; mouse pathology
ID NORMAL-TISSUES; MICE; ANTIBODIES; REACTIVITY; DIAGNOSIS; PATHOLOGY;
UTILITY; LESIONS; IMMUNE; SYSTEM
AB Immunohistochemistry (IHC) is a common adjunct in pathology for morphologic diagnosis, research pathology, and studying the pathogenesis of the disease. Proper technique and interpretation of an immunohistochemistry assay is of utmost importance. A variety of problems, including the presence of artifacts (nonspecific background or other staining problems) and the differentiation between nonspecific and specific staining, commonly occur. It is essential that antibody quality and IHC technique be optimized. We review the histologic patterns of specific and nonspecific staining after using IHC techniques, as well as basic troubleshooting procedures, and provide some examples of nonspecific staining and other artifacts especially in formalin-fixed, paraffin-embedded tissues (FFPE) of mice.
C1 [Ward, J. M.] Global VetPathol, Montgomery Village, MD USA.
[Ward, J. M.] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Rehg, J. E.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
RP Ward, JM (reprint author), NIAID, VCIS, LIG, NIH, MS 8152,Twinbrook 1,Room 1518, Bethesda, MD 20892 USA.
EM veterinarypathology@gmail.com
FU National Cancer Institute [P30C CA 21765]; American Lebanese Syrian
Associated Charities (ALSAC)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship and/or publication of this article: This
publication was supported, in part, by grant P30C CA 21765 from the
National Cancer Institute and by the American Lebanese Syrian Associated
Charities (ALSAC). Its contents are solely the responsibility of the
authors and do not necessary represent the official view of the National
Cancer Institute.
NR 22
TC 5
Z9 5
U1 0
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD JAN
PY 2014
VL 51
IS 1
BP 88
EP 101
DI 10.1177/0300985813503571
PG 14
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 284UY
UT WOS:000329347900006
PM 24078006
ER
PT J
AU Ramos-Vara, JA
Webster, JD
DuSold, D
Miller, MA
AF Ramos-Vara, J. A.
Webster, J. D.
DuSold, D.
Miller, M. A.
TI Immunohistochemical Evaluation of the Effects of Paraffin Section
Storage on Biomarker Stability
SO VETERINARY PATHOLOGY
LA English
DT Article
DE cell markers; immunohistochemistry; infectious diseases; paraffin
section storage; photo-oxidation; antigen decay; tissue-based biomarkers
ID MARKER-IMMUNOSTAINING INTENSITY; EMBEDDED TISSUE-SECTIONS; P53 ANTIGEN
LOSS; STORED PARAFFIN; BREAST-CANCER; DIAGNOSTIC IMMUNOHISTOCHEMISTRY;
EXPRESSION ANALYSIS; FORMALIN FIXATION; MOLECULAR-BIOLOGY; ARCHIVAL
TISSUE
AB Environmental stresses can alter immunoreactivity of biomarkers in stored tissue sections. The effect of temperature and lighting on 49 cellular or microbial antigens was evaluated in 4 serial paraffin sections, cut 12 months, 10 months, 8 months, 5 months, 3 months, 1month, 3 days, and 1day before immunohistochemistry. Slides were stored at room temperature (RT) in the dark, at 4 degrees C in the dark, at RT under fluorescent light, or at RT with windowpane exposure to sunlight. Immunohistochemistry was performed simultaneously in an automated immunostainer. Immunoreactivity was compared with that in the corresponding 1-day-old section and scored as 4 (<10% reduction), 3 (10%-25% reduction), 2 (26%-60% reduction), 1(>60% reduction), or 0 (no reactivity). Any loss of immunoreactivity was proportional to the tissue section age and was least in sections stored in the dark. Immunoreactivity was only completely lost in light-exposed sections and as early as 1month for CD45. Other markers with complete loss of immunoreactivity were bovine viral diarrhea virus, CD18 (only with fluorescent light), CD31, CD68, canine parvovirus, chromogranins, and thyroid transcription factor-1. Markers with complete loss after light exposure also had reduced immunoreactivity when stored in the dark, as early as day 3. Eight markers (Bartonella spp, CD11d, high molecular weight cytokeratins, feline coronavirus, GATA-4, insulin, p63, progesterone receptor) had minimal decrease in immunoreactivity, regardless of treatment. In conclusion, light-induced antigen decay (tissue section aging) is antigen dependent and could explain unexpectedly weak or negative immunohistochemical reactions in stored paraffin sections.
C1 [Ramos-Vara, J. A.; DuSold, D.; Miller, M. A.] Purdue Univ, Anim Dis Diagnost Lab, W Lafayette, IN 47907 USA.
[Ramos-Vara, J. A.; DuSold, D.; Miller, M. A.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA.
[Webster, J. D.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Ramos-Vara, JA (reprint author), Purdue Univ, Anim Dis Diagnost Lab, 406 South Univ, W Lafayette, IN 47907 USA.
EM ramosja@purdue.edu
NR 59
TC 5
Z9 5
U1 2
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD JAN
PY 2014
VL 51
IS 1
BP 102
EP 109
DI 10.1177/0300985813476067
PG 8
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 284UY
UT WOS:000329347900007
PM 23435571
ER
PT J
AU Tabe, Y
Jin, LH
Konopleva, M
Shikami, M
Kimura, S
Andreeff, M
Raffeld, M
Miida, T
AF Tabe, Yoko
Jin, Linhua
Konopleva, Marina
Shikami, Masato
Kimura, Shinya
Andreeff, Michael
Raffeld, Mark
Miida, Takashi
TI Class IA Phosphatidylinositol 3-Kinase Inhibition Inhibits Cell Growth
and Proliferation in Mantle Cell Lymphoma
SO ACTA HAEMATOLOGICA
LA English
DT Article
DE Akt; BCR signaling; Class IA phosphatidylinositol 3-kinase; Mantle cell
lymphoma
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CYCLIN D1; PHOSPHOINOSITIDE 3-KINASE;
P110-DELTA; GENE; KINASE; PI3K; PATHOGENESIS; ACTIVATION; EXPRESSION
AB Background/Aims: Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling pathway preferentially occurs in aggressive blastoid variants of mantle cell lymphoma (MCL) and is implicated in the pathogenesis of this disease. In this study, we investigated the role of PI3K isoforms on proliferation of aggressive MCL cells. Methods:The changes in cell viability, cell cycle distribution and apoptosis induction by the PI3K isoform-selective inhibitors were evaluated. The molecular basis underlying the effects of the specific inhibition of PI3K isoforms was investigated by Western blot analysis. Results: Our results demonstrated that a class IA PI3K isoform is most commonly involved in the constitutive activation of Akt in aggressive MCL. Treatment with a p110 alpha isoform-specific inhibitor induced prominent cell cycle arrest followed by a poptosis through complete abolishment of phosphorylated (p)-Akt and its downstream targets. An inhibitor of isoform p110 delta induced moderate cell cycle arrest with down-regulation of p-Akt and p-S6K. A dual inhibitor of p110 alpha and p110 delta GDC-0941 caused more prominent cell growth inhibition compared to selective p110 alpha or p110 delta inhibitors. Inhibition of the class IB PI3K isoform p110 gamma did not cause cell cycle arrest or induce apoptosis in MCL cells. Conclusion: These findings suggest that the therapeutic ablation of class IA PI3K may be a promising strategy for the treatment of refractory, aggressive MCL. Copyright (C) 2013 S. Karger AG, Basel
C1 [Tabe, Yoko; Jin, Linhua; Miida, Takashi] Juntendo Univ, Sch Med, Dept Clin Lab Med, Tokyo, Japan.
[Kimura, Shinya] Saga Univ, Fac Med, Dept Internal Med, Div Hematol Resp Med & Oncol, Honjo, Japan.
[Konopleva, Marina; Andreeff, Michael] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Raffeld, Mark] NCI, Mol Diagnost Sect, Pathol Lab, Bethesda, MD 20892 USA.
RP Tabe, Y (reprint author), Juntendo Univ, Sch Med, Dept Clin Lab Med, 2-1-1 Bunkyo Ku, Hongo, Tokyo, Japan.
EM tabe@juntendo.ac.jp
RI Miida, Takashi/A-5589-2012
OI Miida, Takashi/0000-0002-4294-8030
FU Institute for Environmental and Gender-specific Medicine, Juntendo
University; Project Research Program of the Juntendo University School
of Medicine
FX This work was supported in part by the Institute for Environmental and
Gender-specific Medicine, Juntendo University, and by the Project
Research Program of the Juntendo University School of Medicine (to
Y.T.).
NR 35
TC 6
Z9 8
U1 0
U2 14
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 0001-5792
EI 1421-9662
J9 ACTA HAEMATOL-BASEL
JI Acta Haematol.
PY 2014
VL 131
IS 1
BP 59
EP 69
DI 10.1159/000353164
PG 11
WC Hematology
SC Hematology
GA 278UN
UT WOS:000328915500010
PM 24052005
ER
PT J
AU Chaves, LF
Scott, TW
Morrison, AC
Takada, T
AF Chaves, Luis Fernando
Scott, Thomas W.
Morrison, Amy C.
Takada, Takenori
TI Hot temperatures can force delayed mosquito outbreaks via sequential
changes in Aedes aegypti demographic parameters in autocorrelated
environments
SO ACTA TROPICA
LA English
DT Article
DE Population delay; Density dependence; Climate change; Trade-offs;
Lefkovitch matrix
ID YELLOW-FEVER MOSQUITO; POPULATION-DYNAMICS; DIPTERA-CULICIDAE;
DENSITY-DEPENDENCE; SEASONAL ABUNDANCE; LIFE-HISTORY; INTRASPECIFIC
COMPETITION; VARIABLE ENVIRONMENTS; INSECT METABOLISM; STEGOMYIA AEGYPTI
AB Aedes aegypti L (Diptera: Culicidae) is a common pantropical urban mosquito, vector of dengue, Yellow Fever and chikungunya viruses. Studies have shown Ae. aegypti abundance to be associated with environmental fluctuations, revealing patterns such as the occurrence of delayed mosquito outbreaks, i.e., sudden extraordinary increases in mosquito abundance following transient extreme high temperatures. Here, we use a two-stage (larvae and adults) matrix model to propose a mechanism for environmental signal canalization into demographic parameters of Ae. aegypti that could explain delayed high temperature induced mosquito outbreaks. We performed model simulations using parameters estimated from a weekly time series from Thailand, assuming either independent or autocorrelated environments. For autocorrelated environments, we found that long delays in the association between the onset of "hot" environments and mosquito outbreaks (10 weeks, as observed in Thailand) can be generated when "hot" environments sequentially trigger a larval survival decrease and over-compensatory fecundity increase, which lasts for the whole "hot" period, in conjunction with a larval survival increase followed by a fecundity decrease when the environment returns to "normal". This result was not observed for independent environments. Finally, we discuss our results implications for prospective entomological research and vector management under changing environments. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Chaves, Luis Fernando] Nagasaki Univ, Inst Trop Med NEKKEN, Nagasaki 8528523, Japan.
[Chaves, Luis Fernando] Univ Nacl, Escuela Medicina Veterinaria, Programa Invest Enfermedades Trop, Heredia, Costa Rica.
[Chaves, Luis Fernando; Takada, Takenori] Hokkaido Univ, Grad Sch Environm Sci, Sapporo, Hokkaido 0600810, Japan.
[Scott, Thomas W.; Morrison, Amy C.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Chaves, LF (reprint author), Nagasaki Univ, Inst Trop Med NEKKEN, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
EM lchaves@nagasaki-u.ac.jp
RI Chaves, Luis Fernando/F-3448-2010
OI Chaves, Luis Fernando/0000-0002-5301-2764
FU Nagasaki University; Japan Society for the Promotion of Science
FX This research was funded by Nagasaki University (Program for Nurturing
Global Leaders in Tropical and Emerging Communicable Diseases and
Cooperative Grant) and Japan Society for the Promotion of Science. This
work also benefited from discussions with working group members in the
Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate, Department of Homeland Security,
and the Fogarty International Center, National Institutes of Health,
USA. LFC and TT wish to dedicate this article to the memory of their
friend Shoichi Yamada, who left too early.
NR 89
TC 12
Z9 13
U1 5
U2 45
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
EI 1873-6254
J9 ACTA TROP
JI Acta Trop.
PD JAN
PY 2014
VL 129
SI SI
BP 15
EP 24
DI 10.1016/j.actatropica.2013.02.025
PG 10
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 278FJ
UT WOS:000328874300002
PM 23537497
ER
PT J
AU O'Seaghdha, CM
Tin, A
Yang, Q
Katz, R
Liu, YM
Harris, T
Astor, B
Coresh, J
Fox, CS
Kao, WHL
Shlipak, MG
AF O'Seaghdha, Conall M.
Tin, Adrienne
Yang, Qiong
Katz, Ronit
Liu, YongMei
Harris, Tamara
Astor, Brad
Coresh, Josef
Fox, Caroline S.
Kao, W. H. Linda
Shlipak, Michael G.
TI Association of a Cystatin C Gene Variant With Cystatin C Levels, CKD,
and Risk of Incident Cardiovascular Disease and Mortality
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Cystatin C; chronic kidney disease; genetics; single-nucleotide
polymorphism; net reclassification improvement
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; GENOME-WIDE
ASSOCIATION; SERUM CREATININE; ELDERLY PERSONS; POOLED ANALYSIS;
RENAL-DISEASE; EQUATION; RECLASSIFICATION; PREDICTION
AB Background: Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFR(cys)). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality.
Study Design: Observational.
Setting&Population: 4 population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Composition (Health ABC) studies.
Predictors: We estimated the association of rs13038305 with eGFR(cys) and serum creatinine-based eGFR (eGFR(cr)) and performed longitudinal analyses of the associations of eGFR(cys) with mortality and cardiovascular events following adjustment for rs13038305.
Outcomes: We assessed reclassification by genotype-adjusted eGFR(cys) across CKD categories:, 45, 45-59, 60-89, and >= 90mL/min/1.73m(2). We compared mortality and CVD outcomes in those reclassified to a worse eGFR(cys) category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis.
Results: In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21%) was associated with a 6.4% lower cystatin C concentration, 5.5-mL/min/1.73m(2) higher eGFR(cys), and 36%[95% CI, 29%-41%] lower odds of CKD. Associations with CVD (HR, 1.17; 95% CI, 1.14-1.20) and mortality (HR, 1.22; 95% CI, 1.19-1.24) per 10-mL/min/1.73m(2) lower eGFR(cys) were similar with or without rs13038305 adjustment. 1,134 (7.7%) participants were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95% CI, 20.003 to 0.022) for mortality and 0.014 (95% CI, 0.0 to 0.028) for CVD.
Limitations: rs13038305 explains only a small proportion of cystatin C variation.
Conclusions: Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Tin, Adrienne; Kao, W. H. Linda] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Katz, Ronit; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94143 USA.
[Katz, Ronit; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Liu, YongMei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Harris, Tamara] Natl Inst Aging, Lab Epidemiol Demog & Biometry, Bethesda, MD USA.
[Astor, Brad] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA.
[Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA.
RP Shlipak, MG (reprint author), Univ Calif San Francisco, 4150 Clement St 111A1, San Francisco, CA 94121 USA.
EM michael.shlipak@ucsf.edu
RI Yang, Qiong/G-5438-2014
FU National Institute on Aging (NIA) [N01AG62101, N01AG62103, N01AG62106,
1R01AG032098-01A1]; National Institutes of Health (NIH)
[HHSN268200782096C]; Intramural Research Program of the NIH, NIA
FX Support: This research was supported by National Institute on Aging
(NIA) contracts N01AG62101, N01AG62103, and N01AG62106. The GWAS was
funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health
Sciences and genotyping services were provided by the Center for
Inherited Disease Research (CIDR). CIDR is fully funded through a
federal contract from the National Institutes of Health (NIH) to The
Johns Hopkins University, contract HHSN268200782096C. This research was
supported in part by the Intramural Research Program of the NIH, NIA.
NR 24
TC 6
Z9 6
U1 1
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JAN
PY 2014
VL 63
IS 1
BP 16
EP 22
DI 10.1053/j.ajkd.2013.06.015
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 281PA
UT WOS:000329112300007
PM 23932088
ER
PT J
AU Dember, LM
Imrey, PB
Beck, GJ
Cheung, AK
Himmelfarb, J
Huber, TS
Kusek, JW
Roy-Chaudhury, P
Vazquez, MA
Alpers, CE
Robbin, ML
Vita, JA
Greene, T
Gassman, JJ
Feldman, HI
AF Dember, Laura M.
Imrey, Peter B.
Beck, Gerald J.
Cheung, Alfred K.
Himmelfarb, Jonathan
Huber, Thomas S.
Kusek, John W.
Roy-Chaudhury, Prabir
Vazquez, Miguel A.
Alpers, Charles E.
Robbin, Michelle L.
Vita, Joseph A.
Greene, Tom
Gassman, Jennifer J.
Feldman, Harold I.
CA Hemodialysis Fistula Maturation St
TI Objectives and Design of the Hemodialysis Fistula Maturation Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Vascular access; arteriovenous fistula; observational
ID PULSE-WAVE VELOCITY; FLOW-MEDIATED VASODILATION; STAGE RENAL-DISEASE;
ARTERIOVENOUS-FISTULA; INTIMAL HYPERPLASIA; BRACHIAL-ARTERY;
GENE-EXPRESSION; ACCESS OUTCOMES; FAILURE; MODEL
AB Background: A large proportion of newly created arteriovenous fistulas cannot be used for dialysis because they fail to mature adequately to support the hemodialysis blood circuit. The Hemodialysis Fistula Maturation (HFM) Studywasdesigned to elucidate clinical and biological factors associated with fistula maturation outcomes.
Study Design: Multicenter prospective cohort study.
Setting & Participants: Approximately 600 patients undergoing creation of a new hemodialysis fistula will be enrolled at 7 centers in the United States and followed up for as long as 4 years.
Predictors: Clinical, anatomical, biological, and process-of-care attributes identified pre-, intra-, or postoperatively.
Outcomes: The primary outcome is unassisted clinical maturation, defined as successful use of the fistula for dialysis for 4 weeks without maturation-enhancing procedures. Secondary outcomes include assisted clinical maturation, ultrasound-based anatomical maturation, fistula procedures, fistula abandonment, and central venous catheter use.
Measurements: Preoperative ultrasound arterial and venous mapping, flow-mediated and nitroglycerin-mediated brachial artery dilation, arterial pulse wave velocity, and venous distensibility; intraoperative vein tissue collection for histopathologic and molecular analyses; postoperative ultrasounds at 1 day, 2 weeks, 6 weeks, and prior to fistula intervention and initial cannulation.
Results: Assuming complete data, no covariate adjustment, and unassisted clinical maturation of 50%, there will be 80% power to detect ORs of 1.83 and 1.61 for dichotomous predictor variables with exposure prevalences of 20% and 50%, respectively.
Limitations: Exclusion of 2-stage transposition fistulas limits generalizability. The requirement for study visits may result in a cohort that is healthier than the overall population of patients undergoing fistula creation.
Conclusions: The HFM Study will be of sufficient size and scope to: (1) evaluate a broad range of mechanistic hypotheses, (2) identify clinical practices associated with maturation outcomes, (3) assess the predictive utility of early indicators of fistula outcome, and (4) establish targets for novel therapeutic interventions to improve fistula maturation. (C) 2013 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Dember, Laura M.; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Imrey, Peter B.; Beck, Gerald J.; Gassman, Jennifer J.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Cheung, Alfred K.] Univ Utah, Sch Med, Nephrol & Hypertens Div, Salt Lake City, UT USA.
[Himmelfarb, Jonathan] Univ Washington, Kidney Res Inst, Div Nephrol, Seattle, WA 98195 USA.
[Huber, Thomas S.] Univ Florida, Coll Med, Div Vasc Surg & Endovasc Therapy, Gainesville, FL USA.
[Kusek, John W.] NIDDK, NIH, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA.
[Roy-Chaudhury, Prabir] Univ Cincinnati, Coll Med, Div Nephrol & Hypertens, Cincinnati, OH USA.
[Vazquez, Miguel A.] Univ Texas Southwestern, Div Nephrol, Dallas, TX USA.
[Alpers, Charles E.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Robbin, Michelle L.] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA.
[Vita, Joseph A.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA.
[Vita, Joseph A.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Greene, Tom] Univ Utah, Sch Med, Div Epidemiol, Salt Lake City, UT USA.
[Feldman, Harold I.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
RP Dember, LM (reprint author), Univ Penn, Perelman Sch Med, Renal Electrolyte & Hypertens Div, 1 Founders,3400 Spruce St, Philadelphia, PA 19104 USA.
EM ldember@upenn.edu
OI Imrey, Peter/0000-0002-0533-4603
FU NIDDK [U01DK066597, U01DK082179, U01DK082189, U01DK082218, U01DK082222,
U01DK082236, U01DK082240]
FX Support: The HFM Study is funded by the following grants from the NIDDK:
U01DK066597, U01DK082179, U01DK082189, U01DK082218, U01DK082222,
U01DK082236, and U01DK082240.
NR 45
TC 26
Z9 28
U1 0
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JAN
PY 2014
VL 63
IS 1
BP 104
EP 112
DI 10.1053/j.ajkd.2013.06.024
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 281PA
UT WOS:000329112300017
PM 23992885
ER
PT J
AU Johnston, JJ
Sapp, JC
Curry, C
Horton, M
Leon, E
Cusmano-Ozog, K
Dobyns, WB
Hudgins, L
Zackai, E
Biesecker, LG
AF Johnston, Jennifer J.
Sapp, Julie C.
Curry, Cynthia
Horton, Margaret
Leon, Eyby
Cusmano-Ozog, Kristina
Dobyns, William B.
Hudgins, Louanne
Zackai, Elaine
Biesecker, Leslie G.
TI Expansion of the TARP Syndrome Phenotype Associated With De Novo
Mutations and Mosaicism
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE TARP; RBM10
ID RBM10; EXONS; GENE
AB The TARP syndrome (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left superior vena cava) is an X-linked disorder that was determined to be caused by mutations in RBM10 in two families, and confirmed in a subsequent case report. The first two original families were quite similar in phenotype, with uniform early lethality although a confirmatory case report showed survival into childhood. Here we report on five affecteds from three newly recognized families, including patients with atypical manifestations. None of the five patients had talipes and others also lacked cardinal TARP features of Robin sequence and atrial septal defect. All three families demonstrated de novo mutations, and one of the families had two recurrences, with demonstrable maternal mosaicism. (c) 2013 Wiley Periodicals, Inc.
C1 [Johnston, Jennifer J.; Sapp, Julie C.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Curry, Cynthia] Fresno Calif State Univ Fresno, Fresno, CA USA.
[Horton, Margaret; Zackai, Elaine] Childrens Hosp Philadelphia, Dept Pediat, Div Genet, Philadelphia, PA 19104 USA.
[Leon, Eyby] Univ Utah, Dept Pediat, Div Genet, Salt Lake City, UT USA.
[Cusmano-Ozog, Kristina; Hudgins, Louanne] Stanford Univ, Dept Pediat, Div Genet, Palo Alto, CA 94304 USA.
[Dobyns, William B.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Dobyns, William B.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Dobyns, William B.] Seattle Childrens Res Inst, Ctr Integrat Brain Res, Seattle, WA USA.
RP Johnston, JJ (reprint author), 49 Convent Dr,Room 4C64, Bethesda, MD 20892 USA.
EM jjohnsto@mail.nih.gov
OI Dobyns, William/0000-0002-7681-2844
FU National Human Genome Research Institute, National Institutes of Health
FX Grant sponsor: National Human Genome Research Institute, National
Institutes of Health.
NR 11
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JAN
PY 2014
VL 164
IS 1
BP 120
EP 128
DI 10.1002/ajmg.a.36212
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 276FV
UT WOS:000328734900017
PM 24259342
ER
PT J
AU Ahmed, A
Bourge, RC
Fonarow, GC
Patel, K
Morgan, CJ
Fleg, JL
Aban, IB
Love, TE
Yancy, CW
Deedwania, P
van Veldhuisen, DJ
Filippatos, GS
Anker, SD
Allman, RM
AF Ahmed, Ali
Bourge, Robert C.
Fonarow, Gregg C.
Patel, Kanan
Morgan, Charity J.
Fleg, Jerome L.
Aban, Inmaculada B.
Love, Thomas E.
Yancy, Clyde W.
Deedwania, Prakash
van Veldhuisen, Dirk J.
Filippatos, Gerasimos S.
Anker, Stefan D.
Allman, Richard M.
TI Digoxin Use and Lower 30-day All-cause Readmission for Medicare
Beneficiaries Hospitalized for Heart Failure
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Digoxin; Heart failure; Hospital readmission
ID CONVERTING ENZYME-INHIBITORS; PRESERVED EJECTION FRACTION; INVESTIGATION
GROUP TRIAL; RENIN-ANGIOTENSIN INHIBITION; CHRONIC KIDNEY-DISEASE;
PROPENSITY-SCORE; CLINICAL EFFECTIVENESS; OLDER PATIENTS; DIG TRIAL;
MORTALITY
AB BACKGROUND: Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown.
METHODS: Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics.
RESULTS: Thirty-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio [HR] for digoxin, 0.77; 95% confidence interval [CI], 0.63-0.95). This beneficial association was observed only in those with ejection fraction < 45% (HR 0.63; 95% CI, 0.47-0.83), but not in those with ejection fraction >= 45% (HR 0.91; 95% CI, 0.60-1.37; P for interaction,.145), a difference that persisted throughout the first 12 months postdischarge (P for interaction, .019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61-0.86) and 0.83 (0.70-0.98), respectively.
CONCLUSIONS: In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Ahmed, Ali; Bourge, Robert C.; Patel, Kanan; Morgan, Charity J.; Aban, Inmaculada B.; Allman, Richard M.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
[Ahmed, Ali; Allman, Richard M.] Vet Affairs Med Ctr, Birmingham, AL USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Love, Thomas E.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Yancy, Clyde W.] Northwestern Univ, Chicago, IL 60611 USA.
[Deedwania, Prakash] Univ Calif San Francisco, Fresno, CA USA.
[van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Filippatos, Gerasimos S.] Attikon Univ Hosp, Athens, Greece.
[Anker, Stefan D.] Campus Virchow Klinikum, Charite, Berlin, Germany.
RP Ahmed, A (reprint author), Univ Alabama Birmingham, 1720 2nd Ave South,CH19,Ste 219, Birmingham, AL 35294 USA.
EM aahmed@uab.edu
RI van Veldhuisen, Dirk Jan/E-8967-2014; Lainscak, Mitja/F-3237-2015
FU National Institutes of Health (NIH) through National Heart, Lung, and
Blood Institute [R01-HL085561, R01-HL085561-S, R01-HL097047]; NIH [UL1
TR000165]
FX AA was in part supported by the National Institutes of Health (NIH)
through grants (R01-HL085561, R01-HL085561-S, and R01-HL097047) from the
National Heart, Lung, and Blood Institute and a generous gift from Ms.
Jean B. Morris of Birmingham, AL. RMA is supported in part by grant
number UL1 TR000165 from NIH.
NR 51
TC 18
Z9 19
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD JAN
PY 2014
VL 127
IS 1
BP 61
EP 70
DI 10.1016/j.amjmed.2013.08.027
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 281UA
UT WOS:000329125300023
PM 24257326
ER
PT J
AU Nygaard, IE
Romero, R
AF Nygaard, Ingrid E.
Romero, Roberto
TI In appreciation of the leadership and stewardship of Drs Thomas J.
Garite and Moon H. Kim
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID PRETERM PREMATURE RUPTURE; FETAL PULSE OXIMETRY; HEART-RATE PATTERNS;
EARLY EMBRYO DEVELOPMENT; JOURNAL-OF-OBSTETRICS; INTRAPARTUM MANAGEMENT;
GROWTH RESTRICTION; CONTROLLED TRIAL; CLINICAL-TRIAL; MEMBRANES
C1 [Nygaard, Ingrid E.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84108 USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
RP Nygaard, IE (reprint author), Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84108 USA.
NR 50
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
BP 1
EP 2
DI 10.1016/j.ajog.2013.10.878
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 281XL
UT WOS:000329134200003
PM 24359865
ER
PT J
AU Romero, R
Badr, MS
AF Romero, Roberto
Badr, M. Safwan
TI A role for sleep disorders in pregnancy complications: challenges and
opportunities
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID PREECLAMPSIA PROSPECTIVE COHORT; GESTATIONAL DIABETES-MELLITUS; POSITIVE
AIRWAY PRESSURE; FETAL-GROWTH RESTRICTION; NEURODEGENERATIVE DISEASES;
INDUCED-HYPERTENSION; BLOOD-PRESSURE; NASAL CPAP; INSULIN SENSITIVITY;
DAYTIME SLEEPINESS
C1 [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Badr, M. Safwan] Wayne State Univ, Dept Med, Div Pulm Crit Care & Sleep Med, Detroit, MI 48202 USA.
RP Romero, R (reprint author), 3990 John R Rd, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
FU Intramural NIH HHS
NR 125
TC 4
Z9 5
U1 2
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
BP 3
EP 11
DI 10.1016/j.ajog.2013.11.020
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 281XL
UT WOS:000329134200004
PM 24359866
ER
PT J
AU Sjaarda, LA
Albert, PS
Mumford, SL
Hinkle, SN
Mendola, P
Laughon, SK
AF Sjaarda, Lindsey A.
Albert, Paul S.
Mumford, Sunni L.
Hinkle, Stefanie N.
Mendola, Pauline
Laughon, S. Katherine
TI Customized large-for-gestational-age birthweight at term and the
association with adverse perinatal outcomes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE customized birthweight; delivery complications; large for gestational
age; macrosomia; neonatal morbidity; neonatal mortality
ID FETAL-GROWTH; INCREASING PREVALENCE; PREGNANCY OUTCOMES;
DIABETES-MELLITUS; RISK; INFANTS; PERCENTILES; POPULATION; MACROSOMIA;
STANDARDS
AB OBJECTIVE: Using a cohort of 110,447 singleton, term pregnancies, we aimed to validate the previously proposed customized standard of large-for-gestational-age (LGA) birthweight, derive an additional customized LGA model excluding maternal weight, and evaluate the association between differing definitions of customized LGA and perinatal morbidities.
STUDY DESIGN: Three customized LGA classifications, in addition to a population-based 90th percentile, were made according to the principals described by Gardosi: (1) customized LGA using Gardosi's previously published coefficients (LGA-Gardosi), (2) customized LGA using coefficients derived by a similar method but from our larger cohort, and (3) derived without customization for maternal weight. Associations between the LGA classifications and various perinatal morbidity outcomes were evaluated.
RESULTS: Coefficients derived here for physiologic and pathologic effects on birthweight were similar to those previously reported by Gardosi. Customized LGA (any method) generally identified more births to younger, nonwhite, nulliparous mothers with female neonates of lower birthweight compared with population-based LGA. Rates of maternal and neonatal morbidity were greatest in births classified by both population-based LGA and customized LGA (any method). However, the model that excluded customization for maternal weight, revealed a greater proportion of women previously unidentified by population-based LGA who were more frequently black (40% vs 25%) and obese (30% vs 5.1%), along with greater rates of shoulder dystocia, neonatal intensive care unit admission and neonatal respiratory complications, than with LGA-Gardosi.
CONCLUSION: The use of customized methods of defining LGA was not decisively superior compared with population-based LGA, but custom LGA may be improved by modification of the parameters included in customization.
C1 [Sjaarda, Lindsey A.; Albert, Paul S.; Mumford, Sunni L.; Hinkle, Stefanie N.; Mendola, Pauline; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
EM laughonsk@mail.nih.gov
RI Hinkle, Stefanie/F-8253-2013;
OI Hinkle, Stefanie/0000-0003-4312-708X; Sjaarda,
Lindsey/0000-0003-0539-8110; Mendola, Pauline/0000-0001-5330-2844;
Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health [HHSN267200603425C]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (contract number
HHSN267200603425C).
NR 35
TC 2
Z9 2
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JAN
PY 2014
VL 210
IS 1
AR 63.e1
DI 10.1016/j.ajog.2013.09.006
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 281XL
UT WOS:000329134200021
PM 24035985
ER
PT J
AU Wei, ZS
Yao, JH
Wang, SJ
Liu, JM
Dwyer, AJ
Pickhardt, PJ
Nowinski, WL
Summers, RM
AF Wei, Zhuoshi
Yao, Jianhua
Wang, Shijun
Liu, Jiamin
Dwyer, Andrew J.
Pickhardt, Perry J.
Nowinski, Wieslaw L.
Summers, Ronald M.
TI Feasibility of Using the Marginal Blood Vessels as Reference Landmarks
for CT Colonography
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE colon; colonic polyps; CT; CT colonography; mesentery; virtual imaging
ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; OPTICAL COLONOSCOPY; FALSE POSITIVES;
POLYP DETECTION; COLONIC POLYPS; SUPINE; PRONE; REGISTRATION;
POPULATION; REDUCTION
AB OBJECTIVE. The purpose of this study was to show the spatial relationship of the colonic marginal blood vessels and the teniae coli on CT colonography (CTC) and the use of the marginal blood vessels for supine-prone registration of polyps and for determination of proper connectivity of collapsed colonic segments.
MATERIALS AND METHODS. We manually labeled the marginal blood vessels on 15 CTC examinations. Colon segmentation, centerline extraction, teniae detection, and teniae identification were automatically performed. For assessment of their spatial relationships, the distances from the marginal blood vessels to the three teniae coli and to the colon were measured. Student t tests (paired, two-tailed) were performed to evaluate the differences among these distances. To evaluate the reliability of the marginal vessels as reference points for polyp correlation, we analyzed 20 polyps from 20 additional patients who underwent supine and prone CTC. The average difference of the circumferential polyp position on the supine and prone scans was computed. Student t tests (paired, two-tailed) were performed to evaluate the supine-prone differences of the distance. We performed a study on 10 CTC studies from 10 patients with collapsed colonic segments by manually tracing the marginal blood vessels near the collapsed regions to resolve the ambiguity of the colon path.
RESULTS. The average distances (+/- SD) from the marginal blood vessels to the tenia mesocolica, tenia omentalis, and tenia libera were 20.1 +/- 3.1 mm (95% CI, 18.5-21.6 mm), 39.5 +/- 4.8 mm (37.1-42.0 mm), and 36.9 +/- 4.2 mm (34.8-39.1 mm), respectively. Pairwise comparison showed that these distances to the tenia libera and tenia omentalis were significantly different from the distance to the tenia mesocolica (p < 0.001). The average distance from the marginal blood vessels to the colon wall was 15.3 +/- 2.0 mm (14.2-16.3 mm). For polyp localization, the average difference of the circumferential polyp position on the supine and prone scans was 9.6 +/- 9.4 mm (5.5-13.7 mm) (p = 0.15) and expressed as a percentage of the colon circumference was 3.1% +/- 2.0% (2.3-4.0%) (p = 0.83). We were able to trace the marginal blood vessels for 10 collapsed colonic segments and determine the paths of the colon in these regions.
CONCLUSION. The marginal blood vessels run parallel to the colon in proximity to the tenia mesocolica and enable accurate supine-prone registration of polyps and localization of the colon path in areas of collapse. Thus, the marginal blood vessels may be used as reference landmarks complementary to the colon centerline and teniae coli.
C1 [Wei, Zhuoshi; Yao, Jianhua; Wang, Shijun; Liu, Jiamin; Dwyer, Andrew J.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Nowinski, Wieslaw L.] Agcy Sci Technol & Res, Singapore Bioimaging Consortium, Biomed Imaging Lab, Singapore, Singapore.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Rm 1C224D,MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health Clinical Center; iCAD
FX This research was supported by the Intramural Research Program of the
National Institutes of Health Clinical Center.; R. M. Summers and J. Yao
have patents (pending or awarded) for related automated analyses for CT
colonography. R. M. Summers and J. Yao receive royalty income for a
patent license from iCAD. R. M. Summers's laboratory receives research
support from iCAD and received research software from Viatronix. P. J.
Pickhardt is a consultant for Viatronix, Bracco, iCAD, and Check-Cap and
cofounder of VirtuoCTC.
NR 45
TC 2
Z9 2
U1 0
U2 0
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JAN
PY 2014
VL 202
IS 1
BP W50
EP W58
DI 10.2214/AJR.12.10463
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 281PH
UT WOS:000329113000007
PM 24370165
ER
PT J
AU Mbulaiteye, SM
Pullarkat, ST
Nathwani, BN
Weiss, LM
Rao, N
Emmanuel, B
Lynch, CF
Hernandez, B
Neppalli, V
Hawes, D
Cockburn, MG
Kim, A
Williams, M
Altekruse, S
Bhatia, K
Goodman, MT
Cozen, W
AF Mbulaiteye, Sam M.
Pullarkat, Sheeja T.
Nathwani, Bharat N.
Weiss, Lawrence M.
Rao, Nagesh
Emmanuel, Benjamin
Lynch, Charles F.
Hernandez, Brenda
Neppalli, Vishala
Hawes, Debra
Cockburn, Myles G.
Kim, Andre
Williams, Makeda
Altekruse, Sean
Bhatia, Kishor
Goodman, Marc T.
Cozen, Wendy
TI Epstein-Barr virus patterns in US Burkitt lymphoma tumors from the SEER
residual tissue repository during 1979-2009
SO APMIS
LA English
DT Article
DE Non-hodgkin lymphoma; burkitt lymphoma; epstein-barr virus; MYC; HIV;
AIDS; Africa
ID NON-HODGKIN LYMPHOMAS; UNITED-STATES; EPIDEMIOLOGIC EVIDENCE; DISEASE;
MYC; CELLS; APOPTOSIS; DIAGNOSIS; GENOMICS; ETIOLOGY
AB Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV-encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student's t-test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0-19 to 55% in age group 20-34, and fell to 25% in age group 60+ years, p=0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p=0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p=0.03). EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group.
C1 [Mbulaiteye, Sam M.; Emmanuel, Benjamin; Bhatia, Kishor] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
[Pullarkat, Sheeja T.; Rao, Nagesh] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Nathwani, Bharat N.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Weiss, Lawrence M.] Clarient Inc, Aliso Viejo, CA USA.
[Lynch, Charles F.; Neppalli, Vishala] Univ Iowa, Iowa City, IA USA.
[Hernandez, Brenda; Goodman, Marc T.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Hawes, Debra; Cockburn, Myles G.; Kim, Andre; Cozen, Wendy] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Williams, Makeda] NCI, Dept Hlth & Human Serv, Ctr Global Hlth, NIH, Rockville, MD 20852 USA.
[Altekruse, Sean] NCI, Div Canc Control & Populat Sci, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA.
RP Mbulaiteye, SM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,Execut Plaza South,Rm 7080 MSC 7, Rockville, MD 20852 USA.
EM mbulaits@mail.nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute (NCI), National Institutes of
Health, Department of Health and Human Services by NCI
[HHSN261200900444P, HHSN26120090058 6P, NO1-PC-35143, NO1-PC-35137,
N01-PC-35139 N01-PC-2010-00035]; California Department of Health
Services as part of the statewide cancer reporting program; Centers for
Disease Control and Prevention [1U58D P000807-3]
FX This work was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute
(NCI), National Institutes of Health, Department of Health and Human
Services (HHSN261200900444P and HHSN26120090058 6P) by NCI grants to the
participating SEER Registries (NO1-PC-35143 for Iowa, NO1-PC-35137 for
Hawaii, and N01-PC-35139 N01-PC-2010-00035 for Los Angeles), and by a
grant from the California Department of Health Services as part of the
statewide cancer reporting program mandated by California Health and
Safety Code Section 103885 and from the Centers for Disease Control and
Prevention (1U58D P000807-3).
NR 35
TC 7
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0903-4641
EI 1600-0463
J9 APMIS
JI APMIS
PD JAN
PY 2014
VL 122
IS 1
BP 5
EP 15
DI 10.1111/apm.12078
PG 11
WC Immunology; Microbiology; Pathology
SC Immunology; Microbiology; Pathology
GA 278SD
UT WOS:000328909100002
PM 23607450
ER
PT J
AU Plazinska, A
Pajak, K
Rutkowska, E
Jimenez, L
Kozocas, J
Koolpe, G
Tanga, M
Toll, L
Wainer, IW
Jozwiak, K
AF Plazinska, Anita
Pajak, Karolina
Rutkowska, Ewelina
Jimenez, Lucita
Kozocas, Joseph
Koolpe, Gary
Tanga, Mary
Toll, Lawrence
Wainer, Irving W.
Jozwiak, Krzysztof
TI Comparative molecular field analysis of fenoterol derivatives
interacting with an agonist-stabilized form of the beta(2)-adrenergic
receptor
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE beta(2)-Adrenoceptor selective agonist; beta(2)-Adrenoceptor
conformations; Agonist-stabilized conformations; Antagonist-stabilized
conformations; [H-3]-(R,R ')-4 '-methoxyfenoterol
ID DOCKING
AB The beta(2)-adrenergic receptor (beta(2)-AR) agonist [H-3]-(R,R')-methoxyfenoterol was employed as the marker ligand in displacement studies measuring the binding affinities (K-i values) of the stereoisomers of a series of 4'-methoxyfenoterol analogs in which the length of the alkyl substituent at alpha' position was varied from 0 to 3 carbon atoms. The binding affinities of the compounds were additionally determined using the inverse agonist [H-3]-CGP-12177 as the marker ligand and the ability of the compounds to stimulate cAMP accumulation, measured as EC50 values, were determined in HEK293 cells expressing the beta(2)-AR. The data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the alpha' position. The results also indicate that the K-i values obtained using [H-3]-(R,R')methoxyfenoterol as the marker ligand modeled the EC50 values obtained from cAMP stimulation better than the data obtained using [H-3]-CGP-12177 as the marker ligand. The data from this study was combined with data from previous studies and processed using the Comparative Molecular Field Analysis approach to produce a CoMFA model reflecting the binding to the beta(2)-AR conformation probed by [H-3]-(R,R')-4'-methoxyfenoterol. The CoMFA model of the agonist-stabilized beta(2)-AR suggests that the binding of the fenoterol analogs to an agonist-stabilized conformation of the beta(2)-AR is governed to a greater extend by steric effects than binding to the [H-3]-CGP-12177-stabilized conformation(s) in which electrostatic interactions play a more predominate role. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Plazinska, Anita; Pajak, Karolina; Rutkowska, Ewelina; Jozwiak, Krzysztof] Med Univ Lublin, Lublin, Poland.
[Jimenez, Lucita; Kozocas, Joseph; Koolpe, Gary; Tanga, Mary] SRI Int, Menlo Pk, CA 94025 USA.
[Toll, Lawrence] Torrey Pines Inst Mol Studies, Port St Lucie, FL USA.
[Wainer, Irving W.] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Jozwiak, K (reprint author), Med Univ Lublin, Lublin, Poland.
EM krzysztof.jozwiak@umlub.pl
RI Pajak, Karolina/B-7811-2014;
OI Pajak, Karolina/0000-0001-7725-5392; Plazinska,
Anita/0000-0002-3698-2574
FU National Institutes of Health National Institute on Aging [N01-AG31009];
NIA/NIH; Foundation for Polish Science (TEAM Programme)
FX This research was supported by the National Institutes of Health
National Institute on Aging [Contract N01-AG31009] by the Intramural
Research Program of the NIA/NIH; and by the Foundation for Polish
Science (TEAM Programme). The article was developed using the equipment
purchased within the Project 'The equipment of innovative laboratories
doing research on new medicines used in the therapy of civilization and
neoplastic diseases' within the Operational Program Development of
Eastern Poland 2007-2013, Priority Axis I Modern Economy, Operations I.3
Innovation Promotion.
NR 16
TC 6
Z9 6
U1 1
U2 16
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JAN 1
PY 2014
VL 22
IS 1
BP 234
EP 246
DI 10.1016/j.bmc.2013.11.030
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 280ZD
UT WOS:000329068400019
PM 24326276
ER
PT J
AU Slobounov, S
Bazarian, J
Bigler, E
Cantu, R
Hallett, M
Harbaugh, R
Hovda, D
Mayer, AR
Nuwer, MR
Kou, Z
Lazzarino, G
Papa, L
Vagnozzi, R
AF Slobounov, Semyon
Bazarian, Jeff
Bigler, Erin
Cantu, Robert
Hallett, Mark
Harbaugh, Robert
Hovda, David
Mayer, Andrew R.
Nuwer, Marc R.
Kou, Zhifeng
Lazzarino, Giuseppe
Papa, Linda
Vagnozzi, Roberto
TI Sports-related concussion: ongoing debate
SO BRITISH JOURNAL OF SPORTS MEDICINE
LA English
DT Editorial Material
DE Concussion
C1 [Slobounov, Semyon] Penn State Univ, Dept Kinesiol & Neurosurg, Penn State Ctr Sports Concuss, Penn State Hershey Med Ctr, University Pk, PA 16802 USA.
[Bazarian, Jeff] Univ Rochester Sch Med & Dent, Dept Emergency Med, Rochester, NY USA.
[Bigler, Erin] Brigham Young Univ, Dept Psychol & Neurosci, Provo, UT 84602 USA.
[Cantu, Robert] Boston Univ Sch Med, Dept Neurosurg, Ctr Study Traumat Encephalopathy, Boston, MA USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Harbaugh, Robert] Penn State Univ Hershey Med Ctr, Penn State Inst Neurosci Engn & Mech, Dept Neurosurg, Hershey, PA USA.
[Hovda, David] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Brain Injury Res Ctr, Dept Neurosurg Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Mayer, Andrew R.] Mind Res Network, Albuquergue, NM USA.
[Nuwer, Marc R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Nuwer, Marc R.] Ronald Reagan UCLA Med Ctr, Dept Clin Neurophysiol, Los Angeles, CA USA.
[Kou, Zhifeng] Wayne State Univ Sch Med, Dept Biomed Engn & Radiol, Detroit, MI USA.
[Lazzarino, Giuseppe] Univ Catania, Dept Biol Geol & Environm Sci, Div Biochem & Mol Biol, I-95124 Catania, Italy.
[Papa, Linda] Orlando Reg Med Ctr Inc, Dept Emergency Med, Orlando, FL USA.
[Vagnozzi, Roberto] Univ Roma Tor Vergata, Sect Neurosurg, Dept Biomed & Prevent, Rome, Italy.
RP Slobounov, S (reprint author), Penn State Univ, Dept Kinesiol & Neurosurg, Penn State Ctr Sports Concuss, Penn State Hershey Med Ctr, 19 Recreation Hall,Univ Pk, University Pk, PA 16802 USA.
EM sms18@psu.edu
OI lazzarino, giuseppe/0000-0002-5917-7279
FU NINDS NIH HHS [R01 NS056227]
NR 0
TC 5
Z9 5
U1 1
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-3674
EI 1473-0480
J9 BRIT J SPORT MED
JI Br. J. Sports Med.
PD JAN
PY 2014
VL 48
IS 2
BP 75
EP 76
DI 10.1136/bjsports-2013-092362
PG 2
WC Sport Sciences
SC Sport Sciences
GA 276KK
UT WOS:000328749000003
PM 23501836
ER
PT J
AU Roth, JE
Peer, CJ
Price, DK
Figg, WD
AF Roth, Jeffrey E.
Peer, Cody J.
Price, Douglas K.
Figg, William D.
TI The androgen receptor transcriptional program in castration-resistant
prostate cancer
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE androgen receptor; binding site; castration-resistant prostate cancer;
transcription factor; transcriptional program
ID CELL-LINES; DISTINCT; PROGRESSION
AB The androgen receptor (AR) is central to the initiation and progression of prostate cancer, even after castration. Its transcriptional activity has previously been studied in cell lines. A group at the University of Cambridge recently outlined the AR transcriptional program in tissue samples, with an emphasis on castration-resistant tumors. AR binding sites, gene-expression changes (in xenografts), and potential transcription factor interactions were notably different from those observed in cultured cells. These discrepancies suggest a distinct signaling network for the AR in vivo and serve as a reminder that results from in vitro models should be checked against clinical realities.
C1 [Roth, Jeffrey E.; Peer, Cody J.; Price, Douglas K.; Figg, William D.] NCI, Clin Pharmacol Program, Off Clin Director, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Off Clin Director, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 14
TC 0
Z9 1
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
EI 1555-8576
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JAN 1
PY 2014
VL 15
IS 1
BP 16
EP 18
DI 10.4161/cbt.27149
PG 3
WC Oncology
SC Oncology
GA 282UV
UT WOS:000329200000003
PM 24253417
ER
PT J
AU Shurin, MR
Umansky, V
Malyguine, A
Hurwitz, AA
Apte, RN
Whiteside, T
Jewett, A
Thanavala, Y
Murphy, WJ
AF Shurin, Michael R.
Umansky, Viktor
Malyguine, Anatoli
Hurwitz, Arthur A.
Apte, Ron N.
Whiteside, Theresa
Jewett, Anahid
Thanavala, Yasmin
Murphy, William J.
TI Cellular and molecular pathways in the tumor immunoenvironment: 3rd
Cancer Immunotherapy and Immunomonitoring (CITIM) meeting, 22-25 April
2013, Krakow, Poland
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Cancer; Immunotherapy; Immunomonitoring; Tumor microenvironment; CITIM
C1 [Shurin, Michael R.; Whiteside, Theresa] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Shurin, Michael R.; Whiteside, Theresa] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Umansky, Viktor] German Canc Res Ctr, Skin Canc Unit, D-69120 Heidelberg, Germany.
[Umansky, Viktor] Heidelberg Univ, Univ Med Ctr Mannheim, Heidelberg, Germany.
[Malyguine, Anatoli] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Hurwitz, Arthur A.] NIH, Frederick, MD USA.
[Apte, Ron N.] Ben Gurion Univ Negev, Beer Sheva, Israel.
[Jewett, Anahid] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Dent & Med, Los Angeles, CA 90024 USA.
[Thanavala, Yasmin] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Murphy, William J.] Univ Calif Davis, Sch Med, Davis, CA 95616 USA.
RP Umansky, V (reprint author), German Canc Res Ctr, Skin Canc Unit, INF 280, D-69120 Heidelberg, Germany.
EM v.umansky@dkfz.de
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank CTL (Cellular Technology Ltd), Europe GmbH, Bonn, Germany;
GTCbio (Global Technology Community), Monrovia, CA, USA; Immatics
Biotechnologies GmbH, Tubingen, Germany; PIVAC; Springer Science +
Business Media B. V.; Cancer Immunology and Immunotherapy; The Journal
of Immunotoxicology; Targi w Krakowie, Krakow, Poland; Lab-JOT Ltd,
Poland; and Jagiellonian Centre of Innovation, Poland, for their
generous support of the CITIM meeting. Anatoli Malyguine has been funded
by the National Cancer Institute, National Institutes of Health, under
Contract No. 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.
NR 0
TC 3
Z9 3
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
EI 1432-0851
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD JAN
PY 2014
VL 63
IS 1
BP 73
EP 80
DI 10.1007/s00262-013-1501-z
PG 8
WC Oncology; Immunology
SC Oncology; Immunology
GA 283EG
UT WOS:000329227700009
PM 24271210
ER
PT J
AU Tian, Y
Ni, DJ
Yang, WB
Zhang, Y
Zhao, KJ
Song, JX
Mao, Q
Tian, ZQ
van Velkinburgh, JC
Yang, D
Wu, YZ
Ni, B
AF Tian, Yi
Ni, Dongjing
Yang, Weibing
Zhang, Yi
Zhao, Keji
Song, Jianxun
Mao, Qing
Tian, Zhiqiang
van Velkinburgh, Jennifer C.
Yang, Di
Wu, Yuzhang
Ni, Bing
TI Telbivudine treatment corrects HBV-induced epigenetic alterations in
liver cells of patients with chronic hepatitis B
SO CARCINOGENESIS
LA English
DT Article
ID VIRUS-PARTICLES; HEPATOCELLULAR-CARCINOMA; HUMAN GENOME; EXPRESSION;
CHROMATIN; GENE; ALPHA-1-ANTITRYPSIN; TRANSCRIPTION; METHYLATIONS;
PATHOGENESIS
AB Hepatitis B virus (HBV) alters the expression of host cellular genes to support its replication and survival and to promote the liver cell injury. However, the underlying mechanism remained incompletely understood. In this study, we investigated HBV-induced epigenetic changes in HepG2 cells by profiling the landscapes of the active histone modification mark H3K4me3 and repressive mark H3K27me3 using chromatin immunoprecipitation-sequencing. HBV caused the altered histone modifications at thousands of genomic loci, which are critically involved in HBV entry, inflammation, fibrosis and carcinogenesis of host cells. Interestingly, treatment of the HBV-transformed HepG2 cells with the anti-HBV drug Telbivudine substantially restored the H3K4me3 level to that of untransformed HepG2 cells. More importantly, our analysis of liver samples from control and chronic hepatitis B patients revealed that treatment of the patients with Telbivudine not only corrected the target gene expression but also the epigenetic modification of critical genes. In addition, the expression of the histone methyltransferases SMYD3 and EZH2 that regulate histone H3-specific methylation showed no difference in HepG2 cell with or without HBV existence. Thus, our data suggest that abnormal histone modifications might critically involved in HBV-mediated liver pathogenesis and Telbivudine therapy might benefit patients with HBV-related chronic infection, liver cirrhosis and even hepatic carcinoma.
Summary: Telbivudine substantially restores in vitro and in vivo HBV-caused abnormal expressions and histone H3K4me3 and H3K27me3 modifications at thousands of genomic loci that are involved in the pathogenesis of liver cells, revealing a novel mechanism for HBV-mediated liver damage.
C1 [Tian, Yi; Ni, Dongjing; Zhang, Yi; Tian, Zhiqiang; Yang, Di; Wu, Yuzhang; Ni, Bing] Third Mil Med Univ, PLA, Inst Immunol, Chongqing 400038, Peoples R China.
[Yang, Weibing] 181th Hosp PLA, Dept Dermatol, Guilin 541002, Peoples R China.
[Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Song, Jianxun] Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA.
[Mao, Qing] Third Mil Med Univ, Southwestern Hosp, Dept Infect Dis, Chongqing 400038, Peoples R China.
[van Velkinburgh, Jennifer C.] van Velkinburgh Initiat Collaboratory BioMed Res, Santa Fe, NM 87501 USA.
RP Ni, B (reprint author), Third Mil Med Univ, PLA, Inst Immunol, Chongqing 400038, Peoples R China.
EM wuyuzhang@yahoo.com; nibingxi@yahoo.com
RI van Velkinburgh, Jennifer/D-7205-2015;
OI van Velkinburgh, Jennifer/0000-0002-4592-2397; Ni,
Bing/0000-0002-4297-5346
FU Major State Basic Research Development Program of China [2013CB531503];
NSFC [30930086, 81220108024, 31070798, 31200668]; Program for Changjiang
Scholars and Innovative Research Team in University [PCSIRT 10521];
Chongqing Science & Technology Commission [CSTC 2009BB5145]
FX Major State Basic Research Development Program of China (2013CB531503);
Major Project of NSFC (30930086); Major Collaborative Project of NSFC
(81220108024); General Program of NSFC (31070798 and 31200668); Program
for Changjiang Scholars and Innovative Research Team in University
(PCSIRT 10521); Chongqing Science & Technology Commission (CSTC
2009BB5145).
NR 37
TC 2
Z9 2
U1 1
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD JAN
PY 2014
VL 35
IS 1
BP 53
EP 61
DI 10.1093/carcin/bgt317
PG 9
WC Oncology
SC Oncology
GA 281WB
UT WOS:000329130600007
PM 24067902
ER
PT J
AU Iyer, S
Perera, F
Zhang, BZ
Chanock, S
Wang, S
Tang, DL
AF Iyer, Shoba
Perera, Frederica
Zhang, Bingzhi
Chanock, Stephen
Wang, Shuang
Tang, Deliang
TI Significant interactions between maternal PAH exposure and haplotypes in
candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking
African-American and Dominican mothers and newborns
SO CARCINOGENESIS
LA English
DT Article
ID POLYCYCLIC AROMATIC-HYDROCARBONS; DNA-ADDUCTS; CAUCASIAN MOTHERS;
EPITHELIAL-CELLS; INDUCTION; CANCER; DAMAGE; BENZO(A)PYRENE; BIOMARKERS;
CYP1B1
AB Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n 132) and Dominican (n 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in geneenvironment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P.
C1 [Iyer, Shoba; Perera, Frederica; Tang, Deliang] Columbia Univ, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA.
[Zhang, Bingzhi; Wang, Shuang] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA.
[Chanock, Stephen] NCI, Gaithersburg, MD 20877 USA.
RP Tang, DL (reprint author), Columbia Univ, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA.
EM dt14@columbia.edu
FU US National Institutes of Health [P01 ES009600, R01 ES008977, T32
CA009529]; US Environmental Protection Agency [R827027, RD832141,
RD834509]; Herbert Irving Comprehensive Cancer Center; Core grant [5P30
CA3696]; New York Community Trust
FX US National Institutes of Health (P01 ES009600, R01 ES008977, and
training grant T32 CA009529); the US Environmental Protection Agency
(R827027, RD832141, RD834509); Herbert Irving Comprehensive Cancer
Center; Core grant (5P30 CA3696); New York Community Trust.
NR 26
TC 3
Z9 3
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD JAN
PY 2014
VL 35
IS 1
BP 69
EP 75
DI 10.1093/carcin/bgt339
PG 7
WC Oncology
SC Oncology
GA 281WB
UT WOS:000329130600009
PM 24177223
ER
PT J
AU Tano, JY
Solanki, S
Lee, RH
Smedlund, K
Birnbaumer, L
Vazquez, G
AF Tano, Jean-Yves
Solanki, Sumeet
Lee, Robert H.
Smedlund, Kathryn
Birnbaumer, Lutz
Vazquez, Guillermo
TI Bone marrow deficiency of TRPC3 channel reduces early lesion burden and
necrotic core of advanced plaques in a mouse model of atherosclerosis
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE TRPC3 channel; Macrophage apoptosis; Atherosclerosis; Calcium channels
ID MACROPHAGE APOPTOSIS; APOE(-/-) MICE; EFFEROCYTOSIS; SURVIVAL; NECROSIS;
ATHEROGENESIS; ACTIVATION; MERTK
AB Macrophage apoptosis plays a determinant role in progression of atherosclerotic lesions. An important goal in atherosclerosis research is to identify new components of macrophage apoptosis that can eventually be exploited as molecular targets in strategies aimed at manipulating macrophage function in the lesion. In the previous work from our laboratory, we have shown that transient receptor potential canonical 3 (TRPC3) channel is an obligatory component of survival mechanisms in human and murine macrophages and that TRPC3-deficient non-polarized bone marrow-derived macrophages exhibit increased apoptosis, suggesting that in vivo TRPC3 might influence lesion development. In the present work, we used a bone marrow transplantation strategy as a first approach to examine the impact of macrophage deficiency of TRPC3 on early and advanced atherosclerotic lesions of Apoe(/) mice.
After 3 weeks of high-fat diet, lesions in mice transplanted with bone marrow from Trpc3(/) donors were smaller and with reduced cellularity than controls. Advanced lesions from these mice exhibited reduced necrotic core, less apoptotic macrophages, and increased collagen content and cap thickness. In vitro, TRPC3-deficient macrophages polarized to the M1 phenotype showed reduced apoptosis, whereas both M1 and M2 macrophages had increased efferocytic capacity.
Bone marrow deficiency of TRPC3 has a dual beneficial effect on lesion progression by reducing cellularity at early stages and necrosis in the advanced plaques. Our findings represent the first evidence for a role of a member of the TRPC family of cation channels in mechanisms associated with atherosclerosis.
C1 [Tano, Jean-Yves; Solanki, Sumeet; Lee, Robert H.; Smedlund, Kathryn; Vazquez, Guillermo] Univ Toledo, Dept Physiol & Pharmacol, Toledo, OH 43614 USA.
[Tano, Jean-Yves; Solanki, Sumeet; Lee, Robert H.; Smedlund, Kathryn; Vazquez, Guillermo] Univ Toledo, Ctr Diabet & Endocrine Res, Toledo, OH 43614 USA.
[Birnbaumer, Lutz] NIEHS, Lab Membrane Signaling, Dept Signal Transduct, Durham, NC 27709 USA.
RP Vazquez, G (reprint author), Univ Toledo, Dept Physiol & Pharmacol, Hlth Sci Campus,3000 Transverse Dr, Toledo, OH 43614 USA.
EM guillermo.vazquez@utoledo.edu
OI Smedlund, Kathryn/0000-0002-5746-8419
FU NIH [R01HL111877-01, Z01-ES-101864]; University of Toledo College of
Medicine
FX This study was supported by NIH grant R01HL111877-01 (to G.V.), the
Intramural Research Program of the NIH Project Z01-ES-101864 (to L.B.),
and University of Toledo College of Medicine.
NR 27
TC 12
Z9 13
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JAN 1
PY 2014
VL 101
IS 1
BP 138
EP 144
DI 10.1093/cvr/cvt231
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 280PM
UT WOS:000329043200017
PM 24101197
ER
PT J
AU Belluscio, L
AF Belluscio, L.
TI Understanding plasticity in the olfactory intrabulbar map
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 22nd Congress of the European-Chemoreception-Research-Organization
(ECRO)
CY AUG 27-29, 2013
CL Leuven, BELGIUM
SP European Chemorecept Res Org
C1 [Belluscio, L.] NINDS, NIH, 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 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD JAN
PY 2014
VL 39
IS 1
BP 85
EP 85
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
Neurology; Physiology
GA 280PS
UT WOS:000329043800055
ER
PT J
AU Cheetham, C
Belluscio, L
AF Cheetham, C.
Belluscio, L.
TI Real-time two-photon imaging reveals rapid and continuous plasticity of
sensory input to the mouse olfactory bulb in vivo
SO CHEMICAL SENSES
LA English
DT Meeting Abstract
CT 22nd Congress of the European-Chemoreception-Research-Organization
(ECRO)
CY AUG 27-29, 2013
CL Leuven, BELGIUM
SP European Chemorecept Res Org
C1 [Cheetham, C.; Belluscio, L.] NINDS, NIH, 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 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD JAN
PY 2014
VL 39
IS 1
BP 91
EP 91
PG 1
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
Neurology; Physiology
GA 280PS
UT WOS:000329043800078
ER
PT J
AU Leese, MP
Jourdan, FL
Major, MR
Dohle, W
Hamel, E
Ferrandis, E
Fiore, A
Kasprzyk, PG
Potter, BVL
AF Leese, Mathew P.
Jourdan, Fabrice L.
Major, Meriel R.
Dohle, Wolfgang
Hamel, Ernest
Ferrandis, Eric
Fiore, Ann
Kasprzyk, Philip G.
Potter, Barry V. L.
TI Tetrahydroisoquinolinone-Based Steroidomimetic and Chimeric Microtubule
Disruptors
SO CHEMMEDCHEM
LA English
DT Article
DE colchicine binding; microtubule disruptors; tetrahydroisoquinolines;
tubulin assembly
ID BREAST-CANCER CELLS; MULTITARGETED ANTITUMOR AGENTS; IN-VITRO;
ANTICANCER AGENTS; TUBULIN POLYMERIZATION; ANTIMITOTIC ACTIVITY;
ACTIVE-SITE; ANALOGS; 2-METHOXYESTRADIOL; INHIBITION
AB A structure-activity relationship (SAR) translation strategy was used for the discovery of tetrahydroisoquinoline (THIQ)-based steroidomimetic and chimeric microtubule disruptors based upon a steroidal starting point. A steroid A,B-ring-mimicking THIQ core was connected to methoxyaryl D-ring ring mimics through methylene, carbonyl and sulfonyl linkers to afford a number of steroidomimetic hits (e.g., 7-methoxy-2-(3- methoxybenzyl)-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (20c) GI(50)=2.1M). Optimisation and control experiments demonstrate the complementary SAR of this series and the steroid derivatives that inspired its design. Linkage of the THIQ-based A,B-mimic with the trimethoxyaryl motif prevalent in colchicine site binding microtubule disruptors delivered a series of chimeric molecules whose activity (GI(50)=40nM) surpasses that of the parent steroid derivatives. Validation of this strategy was obtained from the excellent oral activity of 7-methoxy-6-sulfamoyloxy-2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (20z) relative to a benchmark steroidal bis- sulfamate in an in vivo model of multiple myeloma.
C1 [Leese, Mathew P.; Jourdan, Fabrice L.; Major, Meriel R.; Dohle, Wolfgang; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.
[Hamel, Ernest] NCI, Sceening Technol Branch, Frederick, MD 21702 USA.
[Ferrandis, Eric] Inst Rech Henri Beaufour, F-91966 Les Ulis, France.
[Fiore, Ann; Kasprzyk, Philip G.] IPSEN, Milford, MA USA.
RP Leese, MP (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.
EM B.V.L.Potter@bath.ac.uk
FU Sterix Ltd (Slough, UK)
FX This work was supported by Sterix Ltd (Slough, UK), a member of the
IPSEN Group. We thank Alison Smith (University of Bath, UK) for
technical support. We thank Dr. G. R. Pettit (Arizona State University,
USA) for providing CA-4.
NR 52
TC 5
Z9 5
U1 0
U2 7
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD JAN
PY 2014
VL 9
IS 1
BP 85
EP 108
DI 10.1002/cmdc.201300261
PG 24
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 276JX
UT WOS:000328747700008
PM 24124095
ER
PT J
AU Carroll, D
Hallett, V
McDougle, CJ
Aman, MG
McCracken, JT
Tierney, E
Arnold, LE
Sukhodolsky, DG
Lecavalier, L
Handen, BL
Swiezy, N
Johnson, C
Bearss, K
Vitiello, B
Scahill, L
AF Carroll, Devon
Hallett, Victoria
McDougle, Christopher J.
Aman, Michael G.
McCracken, James T.
Tierney, Elaine
Arnold, L. Eugene
Sukhodolsky, Denis G.
Lecavalier, Luc
Handen, Benjamin L.
Swiezy, Naomi
Johnson, Cynthia
Bearss, Karen
Vitiello, Benedetto
Scahill, Lawrence
TI Examination of Aggression and Self-injury in Children with Autism
Spectrum Disorders and Serious Behavioral Problems
SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA
LA English
DT Article
DE Aggression; Self-injury; Autism; Disruptive behavior
ID PERVASIVE DEVELOPMENTAL DISORDERS; PROACTIVE AGGRESSION; YOUNG-PEOPLE;
IMPULSIVE AGGRESSION; ADOLESCENTS; RISPERIDONE; MEDICATION; TRIAL;
PSYCHIATRY; HYPERACTIVITY
AB This study identified subtypes of aggression in a sample of 206 children with autism spectrum disorder (ASD) who participated in 2 risperidone trials. The narratives were derived from a parent interview about each child's 2 most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and nonaggressive. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD.
C1 [Carroll, Devon] Family & Childrens Aid, Danbury, CT USA.
[Hallett, Victoria] Kings Coll London, London, England.
[McDougle, Christopher J.] Harvard Univ, Cambridge, MA 02138 USA.
[Aman, Michael G.; Arnold, L. Eugene; Lecavalier, Luc] Ohio State Univ, Columbus, OH 43210 USA.
[McCracken, James T.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Tierney, Elaine] Kennedy Krieger Baltimore, Baltimore, MD USA.
[Sukhodolsky, Denis G.] Yale Univ, New Haven, CT 06520 USA.
[Handen, Benjamin L.] Univ Pittsburgh, Sch Med, Western Psychiat Inst, Pittsburgh, PA 15260 USA.
[Handen, Benjamin L.] Univ Pittsburgh, Sch Med, Clin UPMC, Pittsburgh, PA 15260 USA.
[Handen, Benjamin L.] Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA USA.
[Johnson, Cynthia] Univ Pittsburgh, Pittsburgh, PA USA.
[Swiezy, Naomi] Indiana Univ, Bloomington, IN 47405 USA.
[Bearss, Karen; Scahill, Lawrence] Emory Univ, Atlanta, GA 30322 USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD USA.
RP Scahill, L (reprint author), Marcus Ctr, 1920 Briarcliff Rd, Atlanta, GA 30329 USA.
EM lawrence.scahill@emory.edu
OI Scahill, Lawrence/0000-0001-5073-1707; Sukhodolsky,
Denis/0000-0002-5401-792X
FU NCATS NIH HHS [UL1 TR001070, UL1 TR001108]; NCRR NIH HHS [UL1 RR024139,
UL1 RR025755, UL1 RR025761]; NIMH NIH HHS [U10MH66764, U10 MH066764, U10
MH066766, U10 MH066768, U10MH66766, U10MH66768]
NR 54
TC 9
Z9 9
U1 1
U2 24
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1056-4993
EI 1558-0490
J9 CHILD ADOL PSYCH CL
JI Child Adolesc. Psychiatr. N. Am.
PD JAN
PY 2014
VL 23
IS 1
BP 57
EP +
DI 10.1016/j.chc.2013.08.002
PG 17
WC Psychiatry
SC Psychiatry
GA 278VG
UT WOS:000328917400006
PM 24231167
ER
PT J
AU Felsenfeld, G
AF Felsenfeld, Gary
TI A Brief History of Epigenetics
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID EUKARYOTIC DNA METHYLATION; NUCLEOSOME CORE PARTICLE; X-CHROMOSOME;
RESTRICTION ENZYMES; CHROMATIN STRUCTURE; ACTIVE CHROMATIN; NUCLEAR
TRANSFER; GENE-ACTION; LYSINE 9; YEAST
AB The term "epigenetics" was originally used to denote the poorly understood processes by which a fertilized zygote developed into a mature, complex organism. With the understanding that all cells of an organism carry the same DNA, and with increased knowledge of mechanisms of gene expression, the definition was changed to focus on ways in which heritable traits can be associated not with changes in nucleotide sequence, but with chemical modifications of DNA, or of the structural and regulatory proteins bound to it. Recent discoveries about the role of these mechanisms in early development may make it desirable to return to the original definition of epigenetics.
C1 NIDDK, NIH, Bethesda, MD 20892 USA.
RP Felsenfeld, G (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM garyf@intra.niddk.nih.gov
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases
FX I am grateful to Dr. John Gurdon for illuminating exchanges, comments,
and advice. This work was supported by the intramural research program
of the National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 76
TC 19
Z9 20
U1 5
U2 33
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD JAN
PY 2014
VL 6
IS 1
AR a018200
DI 10.1101/cshperspect.a018200
PG 10
WC Cell Biology
SC Cell Biology
GA 282ZO
UT WOS:000329214100004
ER
PT J
AU Corton, JC
Cunningham, ML
Hummer, BT
Lau, C
Meek, B
Peters, JM
Popp, JA
Rhomberg, L
Seed, J
Klaunig, JE
AF Corton, J. Christopher
Cunningham, Michael L.
Hummer, B. Timothy
Lau, Christopher
Meek, Bette
Peters, Jeffrey M.
Popp, James A.
Rhomberg, Lorenz
Seed, Jennifer
Klaunig, James E.
TI Mode of action framework analysis for receptor-mediated toxicity: The
peroxisome proliferator-activated receptor alpha (PPAR alpha) as a case
study
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE Di(2-ethylhexyl) phthalate (DEHP); human relevancy framework; key
events; liver cancer; mode of action; NF-kB; oxidative stress;
peroxisome proliferator-activated receptor alpha (PPAR alpha)
ID NF-KAPPA-B; ACYL-COA OXIDASE; TUMOR-NECROSIS-FACTOR; JUNCTIONAL
INTERCELLULAR COMMUNICATION; CONSTITUTIVE ANDROSTANE RECEPTOR;
<4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643;
CIPROFIBRATE-INDUCED HEPATOCARCINOGENESIS; CORONARY-HEART-DISEASE;
RETINOID-X-RECEPTOR; TRANSFERASE TRANSPEPTIDASE ACTIVITY
AB Several therapeutic agents and industrial chemicals induce liver tumors in rodents through the activation of the peroxisome proliferator-activated receptor alpha (PPAR alpha). The cellular and molecular events by which PPAR alpha activators induce rodent hepatocarcinogenesis has been extensively studied and elucidated. This review summarizes the weight of evidence relevant to the hypothesized mode of action (MOA) for PPAR alpha activator-induced rodent hepatocarcinogenesis and identifies gaps in our knowledge of this MOA. Chemical-specific and mechanistic data support concordance of temporal and dose-response relationships for the key events associated with many PPAR alpha activators including a phthalate ester plasticizer di(2-ethylhexyl) phthalate (DEHP) and the drug gemfibrozil. While biologically plausible in humans, the hypothesized key events in the rodent MOA, for PPAR alpha activators, are unlikely to induce liver tumors in humans because of toxicodynamic and biological differences in responses. This conclusion is based on minimal or no effects observed on growth pathways, hepatocellular proliferation and liver tumors in humans and/or species (including hamsters, guinea pigs and cynomolgous monkeys) that are more appropriate human surrogates than mice and rats at overlapping dose levels. Overall, the panel concluded that significant quantitative differences in PPAR alpha activator-induced effects related to liver cancer formation exist between rodents and humans. On the basis of these quantitative differences, most of the workgroup felt that the rodent MOA is "not relevant to humans'' with the remaining members concluding that the MOA is "unlikely to be relevant to humans''. The two groups differed in their level of confidence based on perceived limitations of the quantitative and mechanistic knowledge of the species differences, which for some panel members strongly supports but cannot preclude the absence of effects under unlikely exposure scenarios.
C1 [Corton, J. Christopher; Lau, Christopher; Seed, Jennifer] US EPA, Res Triangle Pk, NC 27711 USA.
[Cunningham, Michael L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Hummer, B. Timothy] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Meek, Bette] Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON, Canada.
[Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Popp, James A.] Stratoxon LLC, Lancaster, PA USA.
[Rhomberg, Lorenz] Gradient Corp, Cambridge, MA 02138 USA.
[Klaunig, James E.] Indiana Univ, Dept Environm Hlth, Indianapolis, IN 46204 USA.
RP Corton, JC (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, 109 TW Alexander Dr,MD B105-03, Res Triangle Pk, NC 27711 USA.
EM corton.chris@epa.gov; jklauni@indiana.edu
FU Alliance for Risk Assessment (ARA); American Chemistry Council (ACC)
Center for Advancing Risk Assessment; CropLife America; CXR Biosciences;
Dow Chemical Company; DuPont; Hamner Institute for Health; Indiana
University Department of Environmental Health; Society for Risk Analysis
(SRA); Society of Toxicology (SOT); 3M Company; Toxicology Excellence
for Risk Assessment (TERA); U.S. EPA National Health and Environmental
Effects Research Laboratory (NHEERL); U.S. EPA Office of Chemical Safety
and Pollution Prevention (OCSPP); U.S. EPA Office of Water (OW); TERA
FX The employment affiliations of the authors are shown on the cover page.
However, this manuscript, including all analyses, interpretations and
opinions expressed are exclusively the work product of the authors and
are not necessarily those of their employers or respective institutions.
Funding and/or in-kind support for the workshop and this manuscript (but
not to the coauthors) were provided by the Alliance for Risk Assessment
(ARA), American Chemistry Council (ACC) Center for Advancing Risk
Assessment, CropLife America, CXR Biosciences, The Dow Chemical Company,
DuPont, The Hamner Institute for Health, Indiana University Department
of Environmental Health, Society for Risk Analysis (SRA), Society of
Toxicology (SOT), 3M Company, Toxicology Excellence for Risk Assessment
(TERA), U.S. EPA National Health and Environmental Effects Research
Laboratory (NHEERL), U.S. EPA Office of Chemical Safety and Pollution
Prevention (OCSPP) and U.S. EPA Office of Water (OW). The National
Institute of Environmental Health Sciences (NIEHS) provided the workshop
venue. Several of the manuscript authors are employed by the
institutions that provided funding for the workshop. Some of the authors
of this manuscript have consulted for government and industry on
receptor-specific related projects, have been or are funded through
grants and by organizations mentioned earlier and/or have served as
reviewers or on committees for related topics. Toxicology Excellence for
Risk Assessment (TERA) was provided funding to organize and run the
workshop. Some case study panel members were offered funding for travel
and lodging associated with the workshop; some of the members accepted
this funding. Funding was also utilized by TERA to coordinate and draft
workshop manuscripts. Additional funding was supplied by The Dow
Chemical Company, 3M Company and DuPont to finalize and submit the
manuscripts. There was no input or review of the manuscripts by these
sponsors. This manuscript was reviewed by the National Health and
Environmental Effects Research Laboratory, U. S. Environmental
Protection Agency and the NIEHS prior to submission, as a matter of
protocol; however, none of those internal reviews altered the scientific
conclusions
NR 381
TC 34
Z9 34
U1 3
U2 38
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-8444
EI 1547-6898
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PD JAN
PY 2014
VL 44
IS 1
BP 1
EP 49
DI 10.3109/10408444.2013.835784
PG 49
WC Toxicology
SC Toxicology
GA 281XG
UT WOS:000329133700001
PM 24180432
ER
PT J
AU Budinsky, RA
Schrenk, D
Simon, T
Van den Berg, M
Reichard, JF
Silkworth, JB
Aylward, LL
Brix, A
Gasiewicz, T
Kaminski, N
Perdew, G
Starr, TB
Walker, NJ
Rowlands, JC
AF Budinsky, R. A.
Schrenk, D.
Simon, T.
Van den Berg, M.
Reichard, J. F.
Silkworth, J. B.
Aylward, L. L.
Brix, A.
Gasiewicz, T.
Kaminski, N.
Perdew, G.
Starr, T. B.
Walker, N. J.
Rowlands, J. C.
TI Mode of action and dose-response framework analysis for
receptor-mediated toxicity: The aryl hydrocarbon receptor as a case
study
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE Dioxin; dose-response assessment; human relevance framework; key events;
liver cancer; mode of action; modulating factors; TCDD
ID SPRAGUE-DAWLEY RATS; ALTERED HEPATIC FOCI; TRANSFORMING-GROWTH-FACTOR;
REACTIVE OXYGEN PRODUCTION; MESSENGER-RNA EXPRESSION; TUMOR-PROMOTING
ACTIVITY; CANCER-RISK ASSESSMENT; DYNAMIC ORGAN-CULTURE; DIOXIN-LIKE
COMPOUNDS; DIBENZO-P-DIOXINS
AB Dioxins and dioxin-like compounds are tumor promoters that cause liver cancer in rats and mice. The aryl hydrocarbon receptor (AHR) has been implicated as a key component in this tumor promotion response. Despite extensive knowledge of the toxicology of dioxins, no mode of action (MOA) hypothesis for their tumorigenicity has been formally documented using the Human Relevance MOA framework developed by the International Programme on Chemical Safety (IPCS). To address this information gap, an expert panel was convened as part of a workshop on receptor-mediated liver tumorigenicity. Liver tumors induced by ligands of the AHR were assessed using data for dioxins and related chemicals as a case study. The panel proposed a MOA beginning with sustained AHR activation, eventually leading to liver tumors via a number of other processes, including increased cell proliferation of previously initiated altered hepatic foci, inhibition of intrafocal apoptosis and proliferation of oval cells. These processes have been identified and grouped as three key events within the hepatocarcinogenic MOA: (1) sustained AHR activation, (2) alterations in cellular growth and homeostasis and (3) pre-neoplastic tissue changes. These key events were identified through application of the Bradford-Hill considerations in terms of both their necessity for the apical event/adverse outcome and their human relevance. The panel identified data supporting the identification and dose-response behavior of key events, alteration of the dose-response by numerous modulating factors and data gaps that potentially impact the MOA. The current effort of applying the systematic frameworks for identifying key events and assessing human relevance to the AHR activation in the tumorigenicity of dioxins and related chemicals is novel at this time. The results should help direct future regulatory efforts and research activities aimed at better understanding the potential human cancer risks associated with dioxin exposure.
C1 [Budinsky, R. A.; Rowlands, J. C.] Dow Chem Co USA, Midland, MI 48674 USA.
[Schrenk, D.] Tech Univ Kaiserslautern, Dept Food Chem & Environm Toxicol, Kaiserslautern, Germany.
[Simon, T.] Ted Simon LLC, Winston, GA USA.
[Van den Berg, M.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Reichard, J. F.] Toxicol Excellence Risk Assessment, Cincinnati, OH USA.
[Silkworth, J. B.] GE Co, Global Res Ctr, Niskayuna, NY USA.
[Aylward, L. L.] Summit Toxicol LLP, Falls Church, VA USA.
[Brix, A.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
[Gasiewicz, T.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Kaminski, N.] Michigan State Univ, Ctr Integrat Toxicol, E Lansing, MI 48824 USA.
[Perdew, G.] Penn State Univ, University Pk, PA 16802 USA.
[Starr, T. B.] TBS Associates, Raleigh, NC USA.
[Walker, N. J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Budinsky, RA (reprint author), Dow Chem Co USA, Bldg 1803 Washington St, Midland, MI 48674 USA.
EM rabudinsky@dow.com
RI Walker, Nigel/D-6583-2012; Aylward, Lesa/F-7418-2012; Simon,
Ted/M-9188-2013
OI Walker, Nigel/0000-0002-9111-6855; Aylward, Lesa/0000-0003-3191-8175;
Simon, Ted/0000-0001-9405-3020
FU Alliance for Risk Assessment (ARA); American Chemistry Council (ACC)
Center for Advancing Risk Assessment; CXR Biosciences; Dow Chemical
Company; DuPont; Hamner Institute for Health; Indiana University
Department of Environmental Health; Society for Risk Analysis (SRA);
Society of Toxicology (SOT); 3M Company; Toxicology Excellence for Risk
Assessment (TERA); U.S. EPA National Health and Environmental Effects
Research Laboratory (NHEERL); U.S. EPA Office of Chemical Safety and
Pollution Prevention (OCSPP); U.S. EPA Office of Water (OW); CropLife
America
FX This manuscript, including all analyses, interpretations and opinions
expressed are exclusively those of the authors and are not necessarily
those of their employers or respective institutions, as indicated on the
cover page. This article may be the work product of an employee or group
of employees of the NIEHS, National Institutes of Health (NIH); however,
the statements, opinions or conclusions contained therein do not
necessarily represent the statements, opinions or conclusions of NIEHS.
This article reflects the views of the authors and does not necessarily
represent views or polices of the U. S. EPA, the U. S. FDA, the European
Chemicals Agency or any of the other authors' affiliations, as indicated
on the cover page. Funding and in-kind support for the workshop and this
manuscript were provided by the Alliance for Risk Assessment (ARA),
American Chemistry Council (ACC) Center for Advancing Risk Assessment,
CropLife America, CXR Biosciences, The Dow Chemical Company, DuPont, The
Hamner Institute for Health, Indiana University Department of
Environmental Health, Society for Risk Analysis (SRA), Society of
Toxicology (SOT), 3M Company, Toxicology Excellence for Risk Assessment
(TERA), U.S. EPA National Health and Environmental Effects Research
Laboratory (NHEERL), U.S. EPA Office of Chemical Safety and Pollution
Prevention (OCSPP) and U.S. EPA Office of Water (OW). The National
Institute of Environmental Health Sciences (NIEHS) for provided the
workshop venue. Many of these organizations have active research and
vested interests in the outcome of this workshop. Several of the
manuscript authors are employed by the institutions that provided
funding for the workshop. Many authors have worked in consulting for
government and industry on receptor-specific related projects, have been
or are funded through grants and by organizations mentioned earlier and
have served as reviewers or on committees for related topics. Toxicology
Excellence for Risk Assessment (TERA) was provided funding to organize
and run the workshop. All case study panel members were offered funding
for travel and lodging to and from the workshop, of which some accepted
and received. Funding remaining after the workshop was utilized by TERA
to begin coordination and drafting of workshop manuscripts. Additional
funding was supplied by The Dow Chemical Company, 3M Company and DuPont
to finalize and submit the manuscript. Honoraria were offered to all
case study leaders and manuscript lead authors for their time drafting
the manuscript, of which some accepted and received. This manuscript has
been reviewed by multiple institutions; however, none of these internal
reviews made substantive changes to the scientific conclusions or
technical approaches and outcomes, and these were made as a matter of
protocol. This manuscript has been reviewed by the National Health and
Environmental Effects Research Laboratory, US Environmental Protection
Agency and approved for publication. Approval does not signify that the
contents necessarily reflect the views and policies of the Agency. The
NIEHS have had the opportunity to review this manuscript prior to
submission. The Dow Chemical Company has also reviewed the AHR
manuscript prior to submission.
NR 418
TC 24
Z9 24
U1 3
U2 33
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1040-8444
EI 1547-6898
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PD JAN
PY 2014
VL 44
IS 1
BP 83
EP 119
DI 10.3109/10408444.2013.835787
PG 37
WC Toxicology
SC Toxicology
GA 281XG
UT WOS:000329133700004
PM 24245878
ER
PT J
AU Stossel, TP
Dale, DC
AF Stossel, Thomas P.
Dale, David C.
TI Editorial introductions
SO CURRENT OPINION IN HEMATOLOGY
LA English
DT Editorial Material
C1 [Stossel, Thomas P.; Dale, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Stossel, Thomas P.] Boston Childrens Hosp, Boston, MA USA.
[Stossel, Thomas P.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
[Stossel, Thomas P.] Harvard Univ, Med School, Cambridge, MA 02138 USA.
[Dale, David C.] Univ Washington, Seattle, WA 98195 USA.
[Dale, David C.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Dale, David C.] NIAID, NIH, Bethesda, MD USA.
RP Stossel, TP (reprint author), Massachusetts Gen Hosp, Div Translat Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1065-6251
EI 1531-7048
J9 CURR OPIN HEMATOL
JI Curr. Opin. Hematol.
PD JAN
PY 2014
VL 21
IS 1
DI 10.1097/MOH.0000000000000013
PG 2
WC Hematology
SC Hematology
GA 282PT
UT WOS:000329185200001
ER
PT J
AU Rice, JR
Boyd, WA
Chandra, D
Smith, MV
Den Besten, PK
Freedman, JH
AF Rice, Julie R.
Boyd, Windy A.
Chandra, Dave
Smith, Marjolein V.
Den Besten, Pamela K.
Freedman, Jonathan H.
TI COMPARISON OF THE TOXICITY OF FLUORIDATION COMPOUNDS IN THE NEMATODE
CAENORHABDITIS ELEGANS
SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
LA English
DT Article
DE Caenorhabditis elegans; Toxicity testing; Fluoride toxicity; Drinking
water; Silicofluoride
ID WATER; MODEL; LEAD
AB Fluorides are commonly added to drinking water in the United States to decrease the incidence of dental caries. Silicofluorides, such as sodium hexafluorosilicate (Na2SiF6) and fluorosilicic acid (H2SiF6), are mainly used for fluoridation, although fluoride salts such as sodium fluoride (NaF) are also used. Interestingly, only the toxicity of NaF has been examined and not that of the more often used silicofluorides. In the present study, the toxicities of NaF, Na2SiF6, and H2SiF6 were compared. The toxicity of these fluorides on the growth, feeding, and reproduction in the alternative toxicological testing organism Caenorhabditis elegans was examined. Exposure to these compounds produced classic concentration-response toxicity profiles. Although the effects of the fluoride compounds varied among the 3 biological endpoints, no differences were found between the 3 compounds, relative to the fluoride ion concentration, in any of the assays. This suggests that silicofluorides have similar toxicity to NaF. Environ Toxicol Chem 2013;33:82-88. (c) 2013 SETAC
C1 [Rice, Julie R.; Boyd, Windy A.] NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Chandra, Dave; Den Besten, Pamela K.] Univ Calif San Francisco, Dept Orofacial Sci, UCSF Sch Dent, San Francisco, CA 94143 USA.
[Smith, Marjolein V.] SRA Int, Res Triangle Pk, NC USA.
[Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Freedman, JH (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM freedma1@niehs.nih.gov
OI Boyd, Windy/0000-0003-3803-3716
FU National Toxicology Program; National Institute of Environmental Health
Sciences, National Institutes of Health [Z01ES102045, Z01ES102046]
FX The authors have no conflicts of interest. This work was supported in
part by the National Toxicology Program and by the Intramural Research
Program of the National Institute of Environmental Health Sciences,
National Institutes of Health (Z01ES102045 and Z01ES102046).
NR 26
TC 7
Z9 8
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0730-7268
EI 1552-8618
J9 ENVIRON TOXICOL CHEM
JI Environ. Toxicol. Chem.
PD JAN
PY 2014
VL 33
IS 1
BP 82
EP 88
DI 10.1002/etc.2394
PG 7
WC Environmental Sciences; Toxicology
SC Environmental Sciences & Ecology; Toxicology
GA 274HQ
UT WOS:000328597800013
PM 24105802
ER
PT J
AU Bataille, MG
Rhayem, Y
Sousa, SB
Libe, R
Dambrun, M
Chevalier, C
Nigou, M
Auzan, C
North, MO
Sa, J
Gomes, L
Salpea, P
Horvath, A
Stratakis, CA
Hamzaoui, N
Bertherat, J
Clauser, E
AF Bataille, M. Guillaud
Rhayem, Y.
Sousa, S. B.
Libe, R.
Dambrun, M.
Chevalier, C.
Nigou, M.
Auzan, C.
North, M. O.
Sa, J.
Gomes, L.
Salpea, P.
Horvath, A.
Stratakis, C. A.
Hamzaoui, N.
Bertherat, J.
Clauser, E.
TI Systematic screening for PRKAR1A gene rearrangement in Carney complex:
identification and functional characterization of a new in-frame
deletion
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID PROTEIN-KINASE-A; NODULAR ADRENOCORTICAL DISEASE; REGULATORY SUBUNIT;
RI-ALPHA; MUTATIONS; PHOSPHODIESTERASE; HYPERPLASIA; MLPA; 1A
AB Background: Point mutations of the PRKAR1A gene are a genetic cause of Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), but in 30% of the patients no mutation is detected.
Objective: Set up a routine-based technique for systematic detection of large deletions or duplications of this gene and functionally characterize these mutations.
Methods: Multiplex ligation-dependent probe amplification (MLPA) of the 12 exons of the PRKAR1A gene was validated and used to detect large rearrangements in 13 typical CNC and 39 confirmed or putative PPNAD without any mutations of the gene. An in-frame deletion was characterized by western blot and bioluminescence resonant energy transfer technique for its interaction with the catalytic subunit.
Results: MLPA allowed identification of exons 3-6 deletion in three patients of a family with typical CNC. The truncated protein is expressed, but rapidly degraded, and does not interact with the protein kinase A catalytic subunit.
Conclusions: MLPA is a powerful technique that may be used following the lack of mutations detected by direct sequencing in patients with bona fide CNC or PPNAD. We report here one such new deletion, as an example. However, these gene defects are not a frequent cause of CNC or PPNAD.
C1 [Bataille, M. Guillaud; Rhayem, Y.; Dambrun, M.; Nigou, M.; North, M. O.; Clauser, E.] Hop Cochin, AP HP, Dept Biol Hormonale, F-75014 Paris, France.
[Bataille, M. Guillaud; Rhayem, Y.; Chevalier, C.; Auzan, C.; Clauser, E.] Univ Paris 05, INSERM, U970, PARCC, F-75015 Paris, France.
[Libe, R.; Bertherat, J.] Hop Cochin, AP HP, Serv Endocrinol, F-75014 Paris, France.
[Bertherat, J.] Univ Paris 05, INSERM, CNRS, Inst Cochin,U1060, F-75015 Paris, France.
[Gomes, L.] Ctr Hosp Coimbra, Dept Pediat, Serv Endocrinol, Coimbra, Portugal.
[Sousa, S. B.; Sa, J.] Ctr Hosp Coimbra, Dept Pediat, Serv Genet Med, Coimbra, Portugal.
[Sousa, S. B.; Sa, J.] Univ Coimbra, Coimbra, Portugal.
[Sousa, S. B.] UCL Inst Child Hlth, Clin & Mol Genet Unit, London, England.
[Salpea, P.; Horvath, A.; Stratakis, C. A.] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Clauser, E (reprint author), Univ Paris 05, INSERM, U970, PARCC, 56 Rue Leblanc, F-75015 Paris, France.
EM eric.clauser@inserm.fr
FU INSERM; Assistance Publique - Hopitaux de Paris
FX This work was supported by recurrent funding from INSERM and Assistance
Publique - Hopitaux de Paris.
NR 21
TC 4
Z9 4
U1 0
U2 1
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD JAN
PY 2014
VL 170
IS 1
BP 151
EP 160
DI 10.1530/EJE-13-0740
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 279LH
UT WOS:000328961000022
ER
PT J
AU Ghoreschi, K
Gadina, M
AF Ghoreschi, Kamran
Gadina, Massimo
TI Jakpot! New small molecules in autoimmune and inflammatory diseases
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE autoimmunity; cytokines; Jak; kinase inhibitor; psoriasis; signal
transduction; Th17
ID ACTIVE RHEUMATOID-ARTHRITIS; PLACEBO-CONTROLLED TRIAL; JANUS KINASE
INHIBITOR; CHRONIC PLAQUE PSORIASIS; DOUBLE-BLIND; T-CELLS; TYROSINE
KINASE; TOFACITINIB CP-690,550; MONOCLONAL-ANTIBODY; MYELOPROLIFERATIVE
DISORDERS
AB Cytokines are key mediators of the development and homeostasis of haematopoietic cells, critical for host defense, but also for the development of autoimmune and inflammatory diseases such as psoriasis or rheumatoid arthritis (RA). Blocking cytokines activity by interfering with the ligand-receptor association has been successfully employed to treat several immune disorders. A subgroup of cytokines signals through receptors requiring the association with a family of cytoplasmic protein tyrosine kinases known as Janus kinases (Jaks). Jaks have recently gained significant attention as therapeutic targets in inflammation and autoimmunity, and several Jak inhibitory small molecules have been developed. The first two Jak inhibitors, tofacitinib and ruxolitinib, have been approved for the treatment of RA and primary myelofibrosis, respectively. Efficacy and safety data suggest that some of these oral Jak inhibitors as well as their topical formulations may soon enter the daily clinical practice for treating patients with psoriasis, lupus erythematosus or other inflammatory skin diseases. While biologics typically target one single cytokine, these new immunomodulators can inhibit signals from multiple cytokines intra-cellularly and therefore could be useful when other therapies are ineffective. Thus, Jak inhibitors may replace some traditional immunosuppressive agents and help patients not responding to previous therapies.
C1 [Ghoreschi, Kamran] Univ Tubingen, Dept Dermatol, Univ Med Ctr, Tubingen, Germany.
[Gadina, Massimo] NIAMSD, Translat Immunol Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA.
RP Gadina, M (reprint author), NIAMSD, NIH, Bldg 10,Room 6D47-A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kamran.ghoreschi@med.uni-tuebingen.de; gadinama@mail.nih.gov
FU Deutsche Forschungsgemeinschaft (DFG) [Sonderforschungsbereich 685];
NIAMS
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG)
Sonderforschungsbereich 685 (KG) and by the NIAMS Intramural Research
Program of (MG). We also would like to thank Mr. Ethan Tyler for support
with the illustration.
NR 69
TC 35
Z9 37
U1 0
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0906-6705
EI 1600-0625
J9 EXP DERMATOL
JI Exp. Dermatol.
PD JAN
PY 2014
VL 23
IS 1
BP 7
EP 11
DI 10.1111/exd.12265
PG 5
WC Dermatology
SC Dermatology
GA 282TU
UT WOS:000329197300002
PM 24131352
ER
PT J
AU Hanson, ML
Hixon, JA
Li, WQ
Felber, BK
Anver, MR
Stewart, CA
Janelsins, BM
Datta, SK
Shen, W
McLean, MH
Durum, SK
AF Hanson, Miranda L.
Hixon, Julie A.
Li, Wenqing
Felber, Barbara K.
Anver, Miriam R.
Stewart, C. Andrew
Janelsins, Brian M.
Datta, Sandip K.
Shen, Wei
McLean, Mairi H.
Durum, Scott K.
TI Oral Delivery of IL-27 Recombinant Bacteria Attenuates Immune Colitis in
Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE Mouse Model; Crohn's Disease; Ulcerative Colitis; Immune Regulation
ID INFLAMMATORY-BOWEL-DISEASE; ACTIVE CROHNS-DISEASE; CD4(+) T-CELLS;
AUTOIMMUNE ENCEPHALOMYELITIS; INTESTINAL INFLAMMATION; HUMAN
INTERLEUKIN-10; ULCERATIVE-COLITIS; INDUCED PATHOLOGY; HELPER-CELLS;
TH17 CELLS
AB BACKGROUND & AIMS: Treatment of inflammatory bowel disease would benefit from specific targeting of therapeutics to the intestine. We developed a strategy for localized delivery of the immunosuppressive cytokine interleukin (IL)-27, which is synthesized actively in situ by the food-grade bacterium Lactococcus lactis (LL-IL-27), and tested its ability to reduce colitis in mice. METHODS: The 2 genes encoding mouse IL-27 were synthesized with optimal codon use for L lactis and joined with a linker; a signal sequence was added to allow for product secretion. The construct was introduced into L lactis. Colitis was induced via transfer of CD4(+)CD45RB(hi) T cells into Rag(-/-) mice to induce colitis; 7.5 weeks later, LL-IL-27 was administered to mice via gavage. Intestinal tissues were collected and analyzed. RESULTS: LL-IL-27 administration protected mice from T-cell transfer-induced enterocolitis and death. LL-IL-27 reduced disease activity scores, pathology features of large and small bowel, and levels of inflammatory cytokines in colonic tissue. LL-IL-27 also reduced the numbers of CD4(+) and IL-17(+) T cells in gut-associated lymphoid tissue. The effects of LL-IL-27 required production of IL-10 by the transferred T cells. LL-IL-27 was more effective than either LL-IL-10 or systemic administration of recombinant IL-27 in reducing colitis in mice. LL-IL-27 also reduced colitis in mice after administration of dextran sodium sulfate. CONCLUSIONS: LL-IL-27 reduces colitis in mice by increasing the production of IL-10. Mucosal delivery of LL-IL-27 could be a more effective and safer therapy for inflammatory bowel disease.
C1 [Hanson, Miranda L.; Hixon, Julie A.; Li, Wenqing; Stewart, C. Andrew; Shen, Wei; McLean, Mairi H.; Durum, Scott K.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Anver, Miriam R.] NCI, Lab Anim Serv Program, Sci Applicat Int Corp, Frederick, MD 21702 USA.
[Janelsins, Brian M.; Datta, Sandip K.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Durum, SK (reprint author), NCI, NIH, Bldg 560,Room 31-71, Frederick, MD 21702 USA.
EM durums@mail.nih.gov
RI Stewart, Charles/G-2470-2012;
OI Datta, Sandip/0000-0003-0243-7815
FU Crohn's and Colitis Foundation of America; Eli and Edythe Broad
Foundation; National Institutes of Health; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX This research was supported in part by grants from the Crohn's and
Colitis Foundation of America and the Eli and Edythe Broad Foundation,
the Intramural Research Program of the National Institutes of Health,
and with federal funds from the National Cancer Institute, National
Institutes of Health (contract HHSN261200800001E).
NR 51
TC 28
Z9 28
U1 0
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JAN
PY 2014
VL 146
IS 1
BP 210
EP +
DI 10.1053/j.gastro.2013.09.060
PG 25
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 276GF
UT WOS:000328736000035
PM 24120477
ER
PT S
AU Parmigiani, G
Boca, S
Ding, J
Trippa, L
AF Parmigiani, Giovanni
Boca, Simina
Ding, Jie
Trippa, Lorenzo
BE Ochs, MF
TI Statistical Tools and R Software for Cancer Driver Probabilities
SO GENE FUNCTION ANALYSIS, 2ND EDITION
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Markov Chain Monte Carlo; Gene mutation; Cancer driver gene
ID FALSE DISCOVERY RATES; COLORECTAL CANCERS; SOMATIC MUTATION;
BAYESIAN-ANALYSIS; HUMAN BREAST
AB This chapter provides a description and illustration of CancerMutationAnalysis and Cancer MutationMCMC, two open source R packages specifically designed for the analysis of somatic mutations in cancer genome studies, at both the gene and gene-set levels.
C1 [Parmigiani, Giovanni; Ding, Jie; Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Boca, Simina] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Parmigiani, G (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
NR 23
TC 0
Z9 0
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 978-1-62703-721-1; 978-1-62703-720-4
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1101
BP 113
EP 134
DI 10.1007/978-1-62703-721-1_7
D2 10.1007/978-1-62703-721-1
PG 22
WC Biochemical Research Methods; Genetics & Heredity; Mathematical &
Computational Biology
SC Biochemistry & Molecular Biology; Genetics & Heredity; Mathematical &
Computational Biology
GA BJH03
UT WOS:000328151100008
PM 24233780
ER
PT J
AU Battle, A
Mostafavi, S
Zhu, XW
Potash, JB
Weissman, MM
McCormick, C
Haudenschild, CD
Beckman, KB
Shi, JX
Mei, R
Urban, AE
Montgomery, SB
Levinson, DF
Koller, D
AF Battle, Alexis
Mostafavi, Sara
Zhu, Xiaowei
Potash, James B.
Weissman, Myrna M.
McCormick, Courtney
Haudenschild, Christian D.
Beckman, Kenneth B.
Shi, Jianxin
Mei, Rui
Urban, Alexander E.
Montgomery, Stephen B.
Levinson, Douglas F.
Koller, Daphne
TI Characterizing the genetic basis of transcriptome diversity through
RNA-sequencing of 922 individuals
SO GENOME RESEARCH
LA English
DT Article
ID MOLECULAR INTERACTION DATABASE; HUMAN GENOME; REGULATORY VARIATION;
EXPRESSION VARIATION; DISEASE; VARIANTS; COMMON; NETWORK; SEQ; CIS
AB Understanding the consequences of regulatory variation in the human genome remains a major challenge, with important implications for understanding gene regulation and interpreting the many disease-risk variants that fall outside of protein-coding regions. Here, we provide a direct window into the regulatory consequences of genetic variation by sequencing RNA from 922 genotyped individuals. We present a comprehensive description of the distribution of regulatory variation-by the specific expression phenotypes altered, the properties of affected genes, and the genomic characteristics of regulatory variants. We detect variants influencing expression of over ten thousand genes, and through the enhanced resolution offered by RNA-sequencing, for the first time we identify thousands of variants associated with specific phenotypes including splicing and allelic expression. Evaluating the effects of both long-range intra-chromosomal and trans (cross-chromosomal) regulation, we observe modularity in the regulatory network, with three-dimensional chromosomal configuration playing a particular role in regulatory modules within each chromosome. We also observe a significant depletion of regulatory variants affecting central and critical genes, along with a trend of reduced effect sizes as variant frequency increases, providing evidence that purifying selection and buffering have limited the deleterious impact of regulatory variation on the cell. Further, generalizing beyond observed variants, we have analyzed the genomic properties of variants associated with expression and splicing and developed a Bayesian model to predict regulatory consequences of genetic variants, applicable to the interpretation of individual genomes and disease studies. Together, these results represent a critical step toward characterizing the complete landscape of human regulatory variation.
C1 [Battle, Alexis; Mostafavi, Sara; Koller, Daphne] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
[Zhu, Xiaowei; Urban, Alexander E.; Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Potash, James B.] Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA.
[Weissman, Myrna M.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[Weissman, Myrna M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[McCormick, Courtney] Illumina Inc, San Diego, CA 92122 USA.
[Haudenschild, Christian D.] Personalis Inc, Menlo Pk, CA 94025 USA.
[Beckman, Kenneth B.] Univ Minnesota, Biomed Genom Ctr, Minneapolis, MN 55455 USA.
[Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Mei, Rui] Centrill Biosci Inc, Palo Alto, CA 94303 USA.
[Montgomery, Stephen B.; Koller, Daphne] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Montgomery, Stephen B.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
RP Koller, D (reprint author), Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
EM koller@cs.stanford.edu
OI Weissman, Myrna/0000-0003-3490-3075
FU National Institute of Mental Health [RC2MH089916, R01MH090941]
FX We would like to thank Hoon Cho for contributions to figure preparation.
This work was supported by National Institute of Mental Health Grants
RC2MH089916 and R01MH090941.
NR 70
TC 94
Z9 94
U1 4
U2 29
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
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD JAN
PY 2014
VL 24
IS 1
BP 14
EP 24
DI 10.1101/gr.155192.113
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 282ID
UT WOS:000329163500002
PM 24092820
ER
PT J
AU Bashirova, AA
Apps, R
Vince, N
Mochalova, Y
Yu, XG
Carrington, M
AF Bashirova, Arman A.
Apps, Richard
Vince, Nicolas
Mochalova, Yelizaveta
Yu, Xu G.
Carrington, Mary
TI Diversity of the human LILRB3/A6 locus encoding a myeloid inhibitory and
activating receptor pair
SO IMMUNOGENETICS
LA English
DT Article
DE Myeloid receptor; LILR; Copy number variation
ID IMMUNOGLOBULIN-LIKE RECEPTORS; CLASS-I MOLECULES; DENDRITIC CELLS;
MYELOMONOCYTIC CELLS; CUTTING EDGE; FAMILY; BIND; GENE
AB Leukocyte immunoglobulin-like receptor (LILR)B3 and LILRA6 represent a pair of inhibitory/activating receptors with identical extracellular domains and unknown ligands. LILRB3 can mediate inhibitory signaling via immunoreceptor tyrosine-based inhibition motifs in its cytoplasmic tail whereas LILRA6 can signal through association with an activating adaptor molecule, FcR gamma, which bears a cytoplasmic tail with an immunoreceptor tyrosine-based activation motif. The receptors are encoded by two highly polymorphic neighboring genes within the leukocyte receptor complex on human chromosome 19. Here, we report that the two genes display similar levels of single nucleotide polymorphisms with the majority of polymorphic sites being identical. In addition, the LILRA6 gene exhibits copy number variation (CNV) whereas LILRB3 does not. A screen of healthy Caucasians indicated that 32 % of the subjects possessed more than two copies of LILRA6, whereas 4 % have only one copy of the gene per diploid genome. Analysis of mRNA expression in the major fractions of PBMCs showed that LILRA6 is primarily expressed in monocytes, similarly to LILRB3, and its expression level correlates with copy number of the gene. We suggest that the LILRA6 CNV may influence the level of the activating receptor on the cell surface, potentially affecting signaling upon LILRB3/A6 ligation.
C1 [Bashirova, Arman A.; Apps, Richard; Vince, Nicolas; Mochalova, Yelizaveta; Carrington, Mary] SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Bashirova, Arman A.; Apps, Richard; Vince, Nicolas; Mochalova, Yelizaveta; Yu, Xu G.; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02114 USA.
[Mochalova, Yelizaveta] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA.
RP Carrington, M (reprint author), SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
FU Frederick National Laboratory for Cancer Research [HHSN261200800001E];
Intramural Research Program of the NIH; Frederick National Lab; Center
for Cancer Research; NIH/NIAID [R01 AI078799]
FX This project has been funded in whole or in part with federal funds from
the Frederick National Laboratory for Cancer Research, under Contract
no. 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 US Government. This
Research was supported in part by the Intramural Research Program of the
NIH, Frederick National Lab, Center for Cancer Research. X.G.Y. was
supported by NIH/NIAID R01 AI078799. We would like to thank Colm
O'huigin, Daniel McVicar, and Ludmila Lyakh for helpful discussions and
the BSP CCR Genetics Core for technical assistance.
NR 24
TC 9
Z9 9
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0093-7711
EI 1432-1211
J9 IMMUNOGENETICS
JI Immunogenetics
PD JAN
PY 2014
VL 66
IS 1
BP 1
EP 8
DI 10.1007/s00251-013-0730-9
PG 8
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 281JJ
UT WOS:000329096900001
PM 24096970
ER
PT J
AU Brubaker, L
Litman, HJ
Rickey, L
Dyer, KY
Markland, AD
Sirls, L
Norton, P
Casiano, E
Paraiso, MFR
Ghetti, C
Rahn, DD
Kusek, JW
AF Brubaker, L.
Litman, H. J.
Rickey, L.
Dyer, K. Y.
Markland, A. D.
Sirls, L.
Norton, P.
Casiano, E.
Paraiso, M. F. R.
Ghetti, C.
Rahn, D. D.
Kusek, J. W.
TI Surgical preparation: are patients "ready" for stress urinary
incontinence surgery?
SO INTERNATIONAL UROGYNECOLOGY JOURNAL
LA English
DT Article
DE Stress incontinence; Mid-urethral sling; Randomized trial; Urodynamics;
Satisfaction; Surgical outcomes
ID FLOOR DYSFUNCTION SURGERY; GOAL ACHIEVEMENT; OUTCOMES; SATISFACTION
AB Patient preparedness for stress urinary incontinence (SUI) surgery is associated with improvements in post-operative satisfaction, symptoms and quality of life (QoL). This planned secondary analysis examined the association of patient preparedness with surgical outcomes, treatment satisfaction and quality of life.
The ValUE trial compared the effect of pre-operative urodynamic studies with a standardized office evaluation of outcomes of SUI surgery at 1 year. In addition to primary and secondary outcome measures, patient satisfaction with treatment was measured using a five-point Likert scale (very dissatisfied to very satisfied) that queried subjects to rate the treatment's effect on overall incontinence, urge incontinence, SUI, and frequency. Preparedness for surgery was assessed using an 11-question Patient Preparedness Questionnaire (PPQ).
Based on PPQ question 11, 4 out of 5 (81 %) of women reported they "agreed" or "strongly agreed" that they were prepared for surgery. Selected demographic and clinical characteristics were similar in unprepared and prepared women. Among SUI severity baseline measures, total UDI score was significantly but weakly associated with preparedness (question 11 of the PPQ; Spearman's r = 0.13, p = 0.001). Although preparedness for surgery was not associated with successful outcomes, it was associated with satisfaction (r (s) = 0.11, p = 0.02) and larger PGI-S improvement (increase; p = 0.008).
Approximately half (48 %) of women "strongly agreed" that they felt prepared for SUI. Women with higher pre-operative preparedness scores were more satisfied, although surgical outcomes did not differ.
C1 [Brubaker, L.] Loyola Univ, Dept OG, Stritch Sch Med, Chicago, IL 60153 USA.
[Brubaker, L.] Loyola Univ, Dept Urol, Stritch Sch Med, Chicago, IL 60153 USA.
[Litman, H. J.] New England Res Inst, Watertown, MA 02172 USA.
[Rickey, L.] Univ Maryland, Dept Urol, Baltimore, MD 21201 USA.
[Dyer, K. Y.] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA.
[Markland, A. D.] Univ Alabama Birmingham, Dept Vet Affairs, Birmingham, AL USA.
[Markland, A. D.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Sirls, L.] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA.
[Norton, P.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Casiano, E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
[Paraiso, M. F. R.] Cleveland Clin, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Ghetti, C.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
[Rahn, D. D.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
[Kusek, J. W.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Brubaker, L (reprint author), Loyola Univ, Dept OG, Stritch Sch Med, 2160 South 1st Ave, Chicago, IL 60153 USA.
EM Lbrubaker@lumc.edu
RI maiza, marisa/L-6168-2013
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01
DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
FX Supported by cooperative agreements from the National Institute of
Diabetes and Digestive and Kidney Diseases, U01 DK58225, U01 DK58229,
U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01
DK60395, U01 DK60397, and U01 DK60401. Support was also provided by the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 13
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-3462
EI 1433-3023
J9 INT UROGYNECOL J
JI Int. Urogynecol. J.
PD JAN
PY 2014
VL 25
IS 1
BP 41
EP 46
DI 10.1007/s00192-013-2184-x
PG 6
WC Obstetrics & Gynecology; Urology & Nephrology
SC Obstetrics & Gynecology; Urology & Nephrology
GA 281JW
UT WOS:000329098400006
PM 23912506
ER
PT J
AU Yanovski, SZ
Yanovski, JA
AF Yanovski, Susan Z.
Yanovski, Jack A.
TI Long-term Drug Treatment for Obesity A Systematic and Clinical Review
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID PLACEBO-CONTROLLED TRIAL; CONTROLLED-RELEASE PHENTERMINE/TOPIRAMATE;
RANDOMIZED CONTROLLED-TRIALS; CARDIOVASCULAR-DISEASE RISK; LIFE-STYLE
INTERVENTION; PRIMARY-CARE PRACTICE; WEIGHT-LOSS; BODY-WEIGHT;
PHARMACOLOGICAL-TREATMENT; ORLISTAT TREATMENT
AB IMPORTANCE Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone.
OBJECTIVE To conduct a systematic review of medications currently approved in the United States for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice.
EVIDENCE REVIEW A PubMed search from inception through September 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently approved obesity medications lasting at least 1 year that had a primary or secondary outcome of body weight change, included at least 50 participants per group, reported at least 50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed.
FINDINGS Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine plus topiramate-extended release at 1 year. The proportion of patients achieving clinically meaningful (at least 5%) weight loss ranges from 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for top-dose phentermine plus topiramate-extended release. All 3 medications produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy.
CONCLUSIONS AND RELEVANCE Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss of at least 5%, clinicians can decrease their patients' exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit.
C1 [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA.
[Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Yanovski, SZ (reprint author), NIDDK, Off Obes Res, 6707 Democracy Blvd,Room 675, Bethesda, MD 20892 USA.
EM sy29f@nih.gov
FU Intramural Research Program of NICHD [1ZIAHD000641]
FX The conduct of this research was supported in part by the Intramural
Research Program of NICHD grant 1ZIAHD000641 (to Dr J. Yanovski). The
National Institute of Diabetes and Digestive and Kidney Diseases and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development had no role in the design and conduct of the study,
collection, management, analysis, or interpretation of the data,
preparation of the manuscript for publication, or decision to submit the
manuscript for publication, but did review the manuscript and approve
its submission.
NR 99
TC 167
Z9 169
U1 8
U2 59
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JAN 1
PY 2014
VL 311
IS 1
BP 74
EP 86
DI 10.1001/jama.2013.281361
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 282HN
UT WOS:000329161400020
PM 24231879
ER
PT J
AU Szefler, SJ
Chmiel, JF
Fitzpatrick, AM
Giacoia, G
Green, TP
Jackson, DJ
Nielsen, HC
Phipatanakul, W
Raissy, HH
AF Szefler, Stanley J.
Chmiel, James F.
Fitzpatrick, Anne M.
Giacoia, George
Green, Thomas P.
Jackson, Daniel J.
Nielsen, Heber C.
Phipatanakul, Wanda
Raissy, Hengameh H.
TI Asthma across the ages: Knowledge gaps in childhood asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; asthma natural history; asthma progression; asthma biomarkers;
childhood asthma; asthma pharmacotherapy
ID RESPIRATORY-SYNCYTIAL-VIRUS; INFLAMMATORY PULMONARY-DISEASES; EXHALED
BREATH CONDENSATE; HUMAN AIRWAY EPITHELIUM; MILD PERSISTENT ASTHMA;
NITRIC-OXIDE SYNTHASE; 1ST 6 YEARS; LUNG-FUNCTION; YOUNG-CHILDREN;
PRESCHOOL-CHILDREN
AB The Eunice Kennedy Shriver National Institute of Child Health and Human Development convened an Asthma Group in response to the Best Pharmaceuticals for Children Act. The overall goal of the Best Pharmaceuticals for Children Act Program is to improve pediatric therapeutics through preclinical and clinical drug trials that lead to drug-labeling changes. Although significant advances have been made in the understanding and management of asthma in adults with appropriately labeled medications, less information is available on the management of asthma in children. Indeed, many medications are inadequately labeled for use in children. In general, the younger the child, the less information there is available to guide clinicians. Because asthma often begins in early childhood, it is incumbent on us to continue to address the primary questions raised in this review and carefully evaluate the medications used to manage asthma in children. Meanwhile, continued efforts should be made in defining effective strategies that reduce the risk of exacerbations. If the areas of defined need are addressed in the coming years, namely prevention of exacerbations and progression of disease, as well as primary intervention, we will see continuing reduction in asthma mortality and morbidity along with improved quality of life for children with asthma.
C1 [Szefler, Stanley J.] Natl Jewish Hlth, Dept Pediat & Pharmacol, Denver, CO 80206 USA.
[Szefler, Stanley J.] Univ Colorado, Sch Med, Denver, CO USA.
[Chmiel, James F.] Rainbow Babies & Childrens Hosp, Univ Hosp, Cleveland, OH 44106 USA.
[Chmiel, James F.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Fitzpatrick, Anne M.] Emory Univ, Atlanta Ctr Dev Lung Biol, Dept Pediat & Childrens Healthcare, Atlanta, GA 30322 USA.
[Giacoia, George] Natl Inst Child Hlth & Dev, Bethesda, MD USA.
[Green, Thomas P.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Jackson, Daniel J.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA.
[Nielsen, Heber C.] Tufts Univ, Sch Med, Tufts Med Ctr, Floating Hosp Children, Boston, MA 02111 USA.
[Phipatanakul, Wanda] Harvard Univ, Boston Childrens Hosp, Boston, MA USA.
[Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA.
[Raissy, Hengameh H.] Univ New Mexico, Sch Med, Dept Pediat, Albuquerque, NM 87131 USA.
RP Szefler, SJ (reprint author), Natl Jewish Hlth, Dept Pediat, 1400 Jackson St, Denver, CO 80206 USA.
EM szeflers@njhealth.org
OI Nielsen, Heber/0000-0002-9382-0539
FU National Heart, Lung, and Blood Institute (NHLBI) AsthmaNet grant [U10
HL098177]; CTSA award [UL1TR000439, UL1TR000454]; AsthmaNet grant [U10
HL098103]; University of Wisconsin CTSA grant through the National
Institutes of Health (NIH) National Center for Advancing Translational
Sciences (NCATS) [UL1TR000427]; NHLBI AsthmaNet grant [U10 HL098102, U10
HL098075]; Harvard Catalyst/the Harvard Clinical and Translational
Science Center (NIH Award) [UL1 RR 025758]; Harvard University; National
Center for Research Resources; National Center for Advancing
Translational Sciences of the NIH [UL1 TR000041]; NHLBI [5U10
HL098075-02]; Colorado CTSA grant from the NCRR/NIH [UL1 RR025780];
NIH/NCATS [UL1 TR000154]; [R21 HL097231]
FX J.F.C. is supported by National Heart, Lung, and Blood Institute (NHLBI)
AsthmaNet grant U10 HL098177 and CTSA award UL1TR000439. A. M. F. is
supported by AsthmaNet grant U10 HL098103 and CTSA award UL1TR000454. D.
J. J. was supported by the University of Wisconsin CTSA grant
UL1TR000427 through the National Institutes of Health (NIH) National
Center for Advancing Translational Sciences (NCATS). H. C. N. is
supported by R21 HL097231. W. P. is supported by NHLBI AsthmaNet grant
U10 HL098102. This work was conducted with the support of Harvard
Catalyst/the Harvard Clinical and Translational Science Center (NIH
Award no. UL1 RR 025758) and financial contributions from Harvard
University and its affiliated academic health care centers. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of Harvard Catalyst, Harvard University,
and its affiliated academic health care centers; and the National Center
for Research Resources or the NIH. H. H. R. is supported by the National
Center for Research Resources and the National Center for Advancing
Translational Sciences of the NIH through grant no. UL1 TR000041 and
NHLBI-funded Clinical Centers for the NHLBI AsthmaNet grant 5U10
HL098075-02. S. J. S. is supported by NHLBI AsthmaNet grant U10 HL098075
and supported in part by Colorado CTSA grant UL1 RR025780 from the
NCRR/NIH and UL1 TR000154 from NIH/NCATS.
NR 106
TC 28
Z9 28
U1 0
U2 13
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2014
VL 133
IS 1
BP 3
EP 15
DI 10.1016/j.jaci.2013.10.018
PG 13
WC Allergy; Immunology
SC Allergy; Immunology
GA 281MM
UT WOS:000329105700001
PM 24290281
ER
PT J
AU Mendola, P
Mannisto, TI
Leishear, K
Reddy, UM
Chen, Z
Laughon, SK
AF Mendola, Pauline
Maennistoe, Tuija I.
Leishear, Kira
Reddy, Uma M.
Chen, Zhen
Laughon, S. Katherine
TI Neonatal health of infants born to mothers with asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Neonatal health; maternal asthma; respiratory distress syndrome;
transient tachypnea of the newborn; neonatal jaundice; preterm birth
ID MATERNAL ASTHMA; PERINATAL OUTCOMES; TRANSIENT TACHYPNEA; CHILDHOOD
ASTHMA; PREGNANT-WOMEN; FETAL-GROWTH; RISK; HOSPITALIZATION;
EPIDEMIOLOGY; METAANALYSIS
AB Background: Maternal asthma is associated with serious pregnancy complications, but newborn morbidity is understudied.
Objective: We wanted to determine whether infants of asthmatic mothers have more neonatal complications.
Methods: The Consortium on Safe Labor (2002-2008), a retrospective cohort, included 223,512 singleton deliveries at >= 23 weeks' gestation. Newborns of mothers with asthma (n = 17,044) were compared with newborns of women without asthma by using logistic regression models with generalized estimating equations to calculate adjusted odds ratios (ORs) and 95% CIs. Electronic medical record data included gestational week at delivery, birth weight, resuscitation, neonatal intensive care unit (NICU) admission, NICU length of stay, hyperbilirubinemia, respiratory distress syndrome, apnea, sepsis, anemia, transient tachypnea of the newborn, infective pneumonia, asphyxia, intracerebral hemorrhage, seizure, cardiomyopathy, periventricular or intraventricular hemorrhage, necrotizing enterocolitis, aspiration, retinopathy of prematurity, and perinatal mortality.
Results: Preterm delivery was associated with maternal asthma for each week after 33 completed weeks of gestation and not earlier. Maternal asthma also increased the adjusted odds of small for gestational age (OR 5 1.10; 95% CI, 1.05-1.16), NICU admission (OR 5 1.12; 95% CI, 1.07-1.17), hyperbilirubinemia (OR 5 1.09; 95% CI, 1.04-1.14), respiratory distress syndrome (OR 5 1.09; 95% CI, 1.01-1.19), transient tachypnea of the newborn (OR 5 1.10; 95% CI, 1.02-1.19), and asphyxia (OR 5 1.34; 95% CI, 1.03-1.75). Findings persisted for term infants (>= 37 weeks) who had additional increased odds of intracerebral hemorrhage (OR 5 1.84; 95% CI, 1.11-3.03) and anemia (OR 5 1.30; 95% CI, 1.04-1.62).
Conclusions: Maternal asthma was associated with prematurity and small for gestational age. Adverse neonatal outcomes, including respiratory complications, hyperbilirubinemia, and NICU admission, were increased in association with maternal asthma even among term deliveries.
C1 [Mendola, Pauline; Maennistoe, Tuija I.; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Rockville, MD USA.
[Leishear, Kira] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
[Reddy, Uma M.] NICHD, Pregnancy & Perinatol Branch, Rockville, MD USA.
[Chen, Zhen] NICHD, DESPR, Bioinformat & Biostat Branch, Rockville, MD USA.
RP Mendola, P (reprint author), NICHHD, 6100 Execut Blvd,Rm 7B03F, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mannisto, Tuija/0000-0002-6382-9153; Mendola,
Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development; Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603425C]
FX Supported by the Intramural Research Program of the National Institutes
of Health, Eunice Kennedy Shriver National Institute of Child Health and
Human Development. The Consortium on Safe Labor was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, through contract no. HHSN267200603425C.
NR 32
TC 8
Z9 8
U1 0
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2014
VL 133
IS 1
BP 85
EP +
DI 10.1016/j.jaci.2013.06.012
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 281MM
UT WOS:000329105700011
PM 23916153
ER
PT J
AU Bertelsen, RJ
Brantsaeter, AL
Magnus, MC
Haugen, M
Myhre, R
Jacobsson, B
Longnecker, MP
Meltzer, HM
London, SJ
AF Bertelsen, Randi J.
Brantsaeter, Anne Lise
Magnus, Maria C.
Haugen, Margaretha
Myhre, Ronny
Jacobsson, Bo
Longnecker, Matthew P.
Meltzer, Helle M.
London, Stephanie J.
TI Probiotic milk consumption in pregnancy and infancy and subsequent
childhood allergic diseases
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Allergy; asthma; eczema; microbiome; Norwegian Mother and Child Cohort
Study; probiotics; rhinoconjunctivitis
ID NORWEGIAN MOTHER; GUT MICROBIOTA; DOUBLE-BLIND; LACTOBACILLUS-RHAMNOSUS;
EPIDEMIOLOGIC RESEARCH; INTESTINAL MICROFLORA; WOMEN; FOOD;
SUPPLEMENTATION; COHORT
AB Background: Whether probiotics, which can influence the microbiome, prevent infant eczema or allergic disease remains an open question. Most studies have focused on high-risk infants.
Objectives: We sought to assess whether consumption of probiotic milk products protects against atopic eczema, rhinoconjunctivitis, and asthma in early childhood in a large population-based pregnancy cohort (the Norwegian Mother and Child Cohort study).
Methods: We examined associations between consumption of probiotic milk products in pregnancy and infancy with questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614 children. Relative risks (RRs) were calculated by using general linear models adjusted for potential confounders.
Results: Consumption of probiotic milk in pregnancy was associated with a slightly reduced relative risk (RR) of atopic eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78-0.98) compared with no consumption during pregnancy. Maternal history of allergic disease did not notably influence the associations. When both the mother (during pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no consumption by either. Probiotic milk consumption was not associated with asthma at 36 months.
Conclusions: In this population-based cohort consumption of probiotic milk products was related to a reduced incidence of atopic eczema and rhinoconjunctivitis, but no association was seen for incidence of asthma by 36 months of age.
C1 [Bertelsen, Randi J.] Norwegian Inst Publ Hlth, Dept Food Water & Cosmet, N-0403 Oslo, Norway.
[Brantsaeter, Anne Lise; Haugen, Margaretha; Meltzer, Helle M.] Norwegian Inst Publ Hlth, Dept Exposure & Risk Assessment, N-0403 Oslo, Norway.
[Magnus, Maria C.] Norwegian Inst Publ Hlth, Dept Chron Dis, N-0403 Oslo, Norway.
[Myhre, Ronny; Jacobsson, Bo] Norwegian Inst Publ Hlth, Dept Genes & Environm, N-0403 Oslo, Norway.
[Bertelsen, Randi J.; Magnus, Maria C.; Longnecker, Matthew P.; London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Jacobsson, Bo] Sahlgrens Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
RP Bertelsen, RJ (reprint author), Norwegian Inst Publ Hlth, Dept Food Water & Cosmet, Div Environm Med, POB 4404, N-0403 Oslo, Norway.
EM randi.jacobsen.bertelsen@fhi.no
RI Brantsaeter, Anne Lise/H-7014-2016;
OI Brantsaeter, Anne Lise/0000-0001-6315-7134; Longnecker,
Matthew/0000-0001-6073-5322; Meltzer, Helle
Margrete/0000-0002-3591-7017; London, Stephanie/0000-0003-4911-5290
FU Norwegian Ministry of Health; Norwegian Ministry of Education and
Research; National Institute of Environmental Health Sciences [N01 ES
75558]; Division of Intramural Research [ZIA ES049019]; National
Institute of Neurological Disorders and Stroke [1 UO1 NS 047537-01];
Norwegian Research Council/FUGE [151918/S10]
FX The Norwegian Mother and Child Cohort Study is supported by the
Norwegian Ministry of Health, the Norwegian Ministry of Education and
Research, the National Institute of Environmental Health Sciences
(contract N01 ES 75558) and the Division of Intramural Research
(contract ZIA ES049019), the National Institute of Neurological
Disorders and Stroke (grant 1 UO1 NS 047537-01), and the Norwegian
Research Council/FUGE (grant 151918/S10).
NR 47
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U1 6
U2 46
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2014
VL 133
IS 1
BP 165
EP +
DI 10.1016/j.jaci.2013.07.032
PG 15
WC Allergy; Immunology
SC Allergy; Immunology
GA 281MM
UT WOS:000329105700023
PM 24034345
ER
PT J
AU Bruno, RD
Boulanger, CA
Rosenfield, SM
Anderson, LH
Lydon, JP
Smith, GH
AF Bruno, Robert D.
Boulanger, Corinne A.
Rosenfield, Sonia M.
Anderson, Lisa H.
Lydon, John P.
Smith, Gilbert H.
TI Paracrine-rescued lobulogenesis in chimeric outgrowths comprising
progesterone-receptor-null mammary epithelium and redirected wild-type
testicular cells
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Progesterone receptor; RANKL; Mammary; Cellular reprogramming
ID GLAND DEVELOPMENT; CANCER-CELLS; DIFFERENTIATION; PROGENITOR;
TUMORIGENESIS; MECHANISMS; FATE
AB We have previously shown that non-mammary and tumorigenic cells can respond to the signals of the mammary niche and alter their cell fate to that of mammary epithelial progenitor cells. Here we tested the hypothesis that paracrine signals from mammary epithelial cells expressing progesterone receptor (PR) are dispensable for redirection of testicular cells, and that re-directed wild-type testicular-derived mammary cells can rescue lobulogenesis of PR-null mammary epithelium by paracrine signaling during pregnancy. We injected PR-null epithelial cells mixed with testicular cells from wild-type adult male mice into cleared fat-pads of recipient mice. The testicular cells were redirected in vivo to mammary epithelial cell fate during regeneration of the mammary epithelium, and persisted in second-generation outgrowths. In the process, the redirected testicular cells rescued the developmentally deficient PR-null cells, signaling them through the paracrine factor RANKL to produce alveolar secretory structures during pregnancy. This is the first demonstration that paracrine signaling required for alveolar development is not required for cellular reprogramming in the mammary gland, and that reprogrammed testicular cells can provide paracrine signals to the surrounding mammary epithelium.
C1 [Bruno, Robert D.; Boulanger, Corinne A.; Rosenfield, Sonia M.; Anderson, Lisa H.; Smith, Gilbert H.] NCI, Mammary Stem Cell Biol Sect, CCBB, CCR, Bethesda, MD 20892 USA.
[Bruno, Robert D.] Old Dominion Univ, Sch Med Diagnost & Translat Sci, Norfolk, VA 23529 USA.
[Lydon, John P.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
RP Smith, GH (reprint author), NCI, Mammary Stem Cell Biol Sect, CCBB, CCR, Bethesda, MD 20892 USA.
EM smithg@mail.nih.gov
OI Bruno, Robert/0000-0003-3329-9478
FU National Cancer Institute Center for Cancer Research; National
Institutes of Health [NICHD: U54 HD-0077495, NCI: CA-77530]
FX This work was funded by the National Cancer Institute Center for Cancer
Research and National Institutes of Health [grant numbers NICHD: U54
HD-0077495 and NCI: CA-77530 to J.P.L.]. Deposited in PMC for release
after 12 months.
NR 18
TC 2
Z9 2
U1 0
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD JAN 1
PY 2014
VL 127
IS 1
BP 27
EP 32
DI 10.1242/jcs.140749
PG 6
WC Cell Biology
SC Cell Biology
GA 281SY
UT WOS:000329122500004
PM 24190884
ER
PT J
AU Paulson, OB
Hossmann, KA
Ingvar, M
Sokoloff, L
AF Paulson, Olaf B.
Hossmann, Konstantin-Alexander
Ingvar, Martin
Sokoloff, Louis
TI In memoriam: Bo K Siesjo, 1930-2013 OBITUARY
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Biographical-Item
C1 [Paulson, Olaf B.] Copenhagen Univ Hosp, Neurosci Ctr, Dept Neurol, Neurobiol Res Unit, Copenhagen, Denmark.
[Hossmann, Konstantin-Alexander] Max Planck Inst Neurol Res, D-50931 Cologne, Germany.
[Ingvar, Martin] Karolinska Inst, Dept Clin Neurosci, Osher Ctr Integrat Med, Stockholm, Sweden.
[Sokoloff, Louis] NIH, Bethesda, MD 20892 USA.
RP Paulson, OB (reprint author), Copenhagen Univ Hosp, Neurosci Ctr, Dept Neurol, Neurobiol Res Unit, Copenhagen, Denmark.
EM olaf.paulson@nru.dk
RI Paulson, Olaf/N-6924-2016;
OI Paulson, Olaf/0000-0001-7712-8596; Ingvar, Martin/0000-0002-9041-5714
NR 1
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JAN
PY 2014
VL 34
IS 1
BP 1
EP 1
DI 10.1038/jcbfm.2013.190
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 282YK
UT WOS:000329210700001
ER
PT J
AU Starbeck-Miller, GR
Badovinac, VP
Barber, DL
Harty, JT
AF Starbeck-Miller, Gabriel R.
Badovinac, Vladimir P.
Barber, Daniel L.
Harty, John T.
TI Cutting Edge: Expression of Fc gamma RIIB Tempers Memory CD8 T Cell
Function In Vivo
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNE-RESPONSES; RECEPTORS; INFECTION; AUTOIMMUNITY; MACROPHAGE;
SELECTION; IGG
AB During reinfection, high-affinity IgG Abs form complexes with both soluble Ag and Ag displayed on the surface of infected cells. These interactions regulate cellular activation of both innate cells and B cells, which express specific combinations of activating Fc gamma Rs (Fc gamma RI, Fc gamma RIII, Fc gamma RIV) and/or the inhibitory Fc gamma R (Fc gamma RIIB). Direct proof for functional expression of Fc gamma R by Ag-specific CD8 T cells is lacking. In this article, we show that the majority of memory CD8 T cells generated by bacterial or viral infection express only Fc gamma RIIB, and that FcgRIIB could be detected on previously activated human CD8 T cells. Of note, Fc gamma R stimulation during in vivo Ag challenge not only inhibited the cytotoxicity of memory CD8 T cells against peptide-loaded or virus-infected targets, but Fc gamma RIIB blockade during homologous virus challenge enhanced the secondary CD8 T cell response. Thus, memory CD8 T cells intrinsically express a functional Fc gamma RIIB, permitting Ag-Ab complexes to regulate secondary CD8 T cell responses.
C1 [Starbeck-Miller, Gabriel R.; Badovinac, Vladimir P.; Harty, John T.] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA.
[Badovinac, Vladimir P.; Harty, John T.] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA.
[Barber, Daniel L.] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Harty, John T.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA.
RP Harty, JT (reprint author), Univ Iowa, Dept Microbiol, 3-530 Bowen Sci Bldg,51 Newton Rd, Iowa City, IA 52242 USA.
EM john-harty@uiowa.edu
RI badovinac, Vladimir/O-7760-2015;
OI Starbeck-Miller, Gabriel/0000-0002-6681-1274
FU National Institutes of Health [T32 AI 007511, AI083286, AI096850,
AI42676, AI85515, AI90850, AI95178, AI96850]
FX This work was supported by National Institutes of Health Grants T32 AI
007511 (to G. R. S.-M.), AI083286 and AI096850 (to V. P. B.), and
AI42676, AI85515, AI90850, AI95178, and AI96850 (to J.T.H.).
NR 39
TC 8
Z9 11
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JAN 1
PY 2014
VL 192
IS 1
BP 35
EP 39
DI 10.4049/jimmunol.1302232
PG 5
WC Immunology
SC Immunology
GA 279HJ
UT WOS:000328950700004
PM 24285839
ER
PT J
AU Brochetta, C
Suzuki, R
Vita, F
Soranzo, MR
Claver, J
Madjene, LC
Attout, T
Vitte, J
Varin-Blank, N
Zabucchi, G
Rivera, J
Blank, U
AF Brochetta, Cristiana
Suzuki, Ryo
Vita, Francesca
Soranzo, Maria Rosa
Claver, Julien
Madjene, Lydia Celia
Attout, Tarik
Vitte, Joana
Varin-Blank, Nadine
Zabucchi, Giuliano
Rivera, Juan
Blank, Ulrich
TI Munc18-2 and Syntaxin 3 Control Distinct Essential Steps in Mast Cell
Degranulation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID LYMPHOHISTIOCYTOSIS TYPE 5; PANCREATIC BETA-CELLS; FC-EPSILON-RI;
REGULATED EXOCYTOSIS; MEMBRANE-FUSION; SEC1/MUNC18 PROTEINS; DEPENDENT
TRANSPORT; CYTOKINE SECRETION; GRANULE EXOCYTOSIS; RBL-2H3 CELLS
AB Mast cell degranulation requires N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) and mammalian uncoordinated18 (Munc18) fusion accessory proteins for membrane fusion. However, it is still unknown how their interaction supports fusion. In this study, we found that small interfering RNA-mediated silencing of the isoform Munc18-2 in mast cells inhibits cytoplasmic secretory granule (SG) release but not CCL2 chemokine secretion. Silencing of its SNARE-binding partner syntaxin 3 (STX3) also markedly inhibited degranulation, whereas combined knockdown produced an additive inhibitory effect. Strikingly, while Munc18-2 silencing impaired SG translocation, silencing of STX3 inhibited fusion, demonstrating unique roles of each protein. Immunogold studies showed that both Munc18-2 and STX3 are located on the granule surface, but also within the granule matrix and in small nocodazole-sensitive clusters of the cytoskeletal meshwork surrounding SG. After stimulation, clusters containing both effectors were detected at fusion sites. In resting cells, Munc18-2, but not STX3, interacted with tubulin. This interaction was sensitive to nocodazole treatment and decreased after stimulation. Our results indicate that Munc18-2 dynamically couples the membrane fusion machinery to the microtubule cytoskeleton and demonstrate that Munc18-2 and STX3 perform distinct, but complementary, functions to support, respectively, SG translocation and membrane fusion in mast cells.
C1 [Brochetta, Cristiana; Claver, Julien; Madjene, Lydia Celia; Attout, Tarik; Vitte, Joana; Blank, Ulrich] INSERM, UMR 699, F-75018 Paris, France.
[Brochetta, Cristiana; Claver, Julien; Madjene, Lydia Celia; Attout, Tarik; Vitte, Joana; Blank, Ulrich] Univ Paris Diderot, Sorbonne Paris Cite, Lab Excellence INFLAMEX, F-75018 Paris, France.
[Suzuki, Ryo; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
[Vita, Francesca; Soranzo, Maria Rosa; Zabucchi, Giuliano] Univ Trieste, Dept Life Sci Physiol & Pathol, I-34127 Trieste, Italy.
[Varin-Blank, Nadine] INSERM, U978, F-93000 Bobigny, France.
[Varin-Blank, Nadine] Univ Paris 13, Sorbonne Paris Cite, Lab Excellence Inflamex, Unite Format & Rech Sante Med Biol Humaine, F-93000 Bobigny, France.
RP Blank, U (reprint author), INSERM, Fac Med X Bichat, U699, 16 Rue Henri Huchard, F-75780 Paris 18, France.
EM ulrich.blank@inserm.fr
RI Vitted, Joana/G-2572-2013
OI Vitted, Joana/0000-0002-3344-9408
FU Investissements d'Avenir Programme [ANR-11-IDEX-0005-02]; Sorbonne Paris
Cite; Laboratoire d'Excellence INFLAMEX; National Institute of Arthritis
and Musculoskeletal and Skin Diseases, National Institutes of Health;
Cooperation in Science and Technology Action of the European Community
[BM1007]; European Community [504926]; Fondation de Recherche Medicale
FX This work was supported by Investissements d'Avenir Programme
ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d'Excellence
INFLAMEX. The work of J.R. and R. S. is supported by the intramural
research program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health. This
work was also supported by Cooperation in Science and Technology Action
BM1007 (Mast cell and basophils-targets for innovative therapies) of the
European Community. The research project of U. B. and C. B. has also
been supported by a Marie Curie Early Stage Research Training Fellowship
of the European Community's Sixth Framework Programme under Contract
504926 and by the Fondation de Recherche Medicale.
NR 70
TC 22
Z9 22
U1 2
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JAN 1
PY 2014
VL 192
IS 1
BP 41
EP 51
DI 10.4049/jimmunol.1301277
PG 11
WC Immunology
SC Immunology
GA 279HJ
UT WOS:000328950700005
PM 24323579
ER
PT J
AU Bowen, S
Sun, P
Livak, F
Sharrow, S
Hodes, RJ
AF Bowen, Steven
Sun, Peter
Livak, Ferenc
Sharrow, Susan
Hodes, Richard J.
TI A Novel T Cell Subset with Trans-Rearranged V gamma-C beta b TCRs Shows
V beta Expression Is Dispensable for Lineage Choice and MHC Restriction
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ANTIGEN RECEPTOR GENES; THYMIC SELECTION; ATAXIA-TELANGIECTASIA;
AMINO-ACIDS; RECOGNITION; CD4; MICE; RECOMBINATION; SPECIFICITY;
REPERTOIRE
AB alpha beta T cells, which express the alpha-beta TCR heterodimer, express CD4 or CD8 coreceptors on cells that are MHC class I or MHC class II dependent. In contrast, gamma delta T cells do not express CD4 or CD8 and develop independently of MHC interaction. The factors that determine alpha beta and gamma delta lineage choice are not fully understood, and the determinants of MHC restriction of TCR specificity have been controversial. In this study we have identified a naturally occurring population of T cells expressing V gamma-C beta receptor chains on the cell surface, the products of genomic trans-rearrangement between the V gamma 2 gene and a variety of D beta or J beta genes, in place of an intact TCR beta-chain and in association with TCR alpha. Identification of this population allowed an analysis of the role of TCR variable regions in determining T cell lineage choice and MHC restriction. We found that V gamma 2(+)C beta(+) cells are positive for either CD4 or CD8 and are selected in an MHC class II- or MHC class I-dependent manner, respectively, thus following the differentiation pathway of alpha beta and not gamma delta cells and demonstrating that V beta V region sequences are not required for selection of an MHCrestricted repertoire.
C1 [Bowen, Steven; Sharrow, Susan; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Sun, Peter] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Livak, Ferenc] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Hodes, RJ (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Room 4B10, Bethesda, MD 20892 USA.
EM Richard_hodes@nih.gov
FU National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health.
NR 32
TC 4
Z9 4
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JAN 1
PY 2014
VL 192
IS 1
BP 169
EP 177
DI 10.4049/jimmunol.1302398
PG 9
WC Immunology
SC Immunology
GA 279HJ
UT WOS:000328950700018
PM 24307734
ER
PT J
AU Cologna, SM
Cluzeau, CVM
Yanjanin, NM
Blank, PS
Dail, MK
Siebel, S
Toth, CL
Wassif, CA
Lieberman, AP
Porter, FD
AF Cologna, Stephanie M.
Cluzeau, Celine V. M.
Yanjanin, Nicole M.
Blank, Paul S.
Dail, Michelle K.
Siebel, Stephan
Toth, Cynthia L.
Wassif, Christopher A.
Lieberman, Andrew P.
Porter, Forbes D.
TI Human and mouse neuroinflammation markers in Niemann-Pick disease, type
C1
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID OXIDATIVE STRESS; UNESTERIFIED CHOLESTEROL; NEUROFIBRILLARY TANGLES;
MURINE MODEL; EVERY ORGAN; NEURODEGENERATION; MICE; MIGLUSTAT;
MICROGLIA; GENE
AB Niemann-Pick disease, type C1 (NPC1) is an autosomal recessive lipid storage disorder in which a pathological cascade, including neuroinflammation occurs. While data demonstrating neuroinflammation is prevalent in mouse models, data from NPC1 patients is lacking. The current study focuses on identifying potential markers of neuroinflammation in NPC1 from both the Npc1 mouse model and NPC1 patients. We identified in the mouse model significant changes in expression of genes associated with inflammation and compared these results to the pattern of expression in human cortex and cerebellar tissue. From gene expression array analysis, complement 3 (C3) was increased in mouse and human post-mortem NPC1 brain tissues. We also characterized protein levels of inflammatory markers in cerebrospinal fluid (CSF) from NPC1 patients and controls. We found increased levels of interleukin 3, chemokine (C-X-C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients. CSF markers were evaluated with respect to phenotypic severity. Miglustat treatment in NPC1 patients slightly decreased IL-3, IL-10 and IL-13 CSF levels; however, further studies are needed to establish a strong effect of miglustat on inflammation markers. The identification of inflammatory markers with altered levels in the cerebrospinal fluid of NPC1 patients may provide a means to follow secondary events in NPC1 disease during therapeutic trials.
C1 [Cologna, Stephanie M.; Cluzeau, Celine V. M.; Yanjanin, Nicole M.; Dail, Michelle K.; Siebel, Stephan; Toth, Cynthia L.; Wassif, Christopher A.; Porter, Forbes D.] NICHD, Program Dev Endocrinol & Genet, Sect Mol Dysmorphol, NIH,DHHS, Bethesda, MD 20892 USA.
[Blank, Paul S.] NICHD, Program Phys Biol, Sect Membrane & Cellular Biophys, NIH,DHHS, Bethesda, MD 20892 USA.
[Lieberman, Andrew P.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
RP Porter, FD (reprint author), NICHD, Program Dev Endocrinol & Genet, Sect Mol Dysmorphol, NIH,DHHS, Bld 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM fdporter@mail.nih.gov
RI Cluzeau, Celine/E-6873-2016;
OI Cluzeau, Celine/0000-0002-7791-6223; Wassif,
Christopher/0000-0002-2524-1420
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Neurological Disorders and Stroke
[R01 NS063967]; NIH Clinical Center; Office of Rare Diseases; National
Niemann-Pick Disease Foundation; Ara Parseghian Medical Research
Foundation (APMRF)
FX Human tissue was obtained from the NICHD Brain and Tissue Bank for
Developmental Disorders at the University of Maryland, Baltimore, MD.
This study was supported by the intramural research program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and by the National Institute of Neurological Disorders and
Stroke (R01 NS063967 to APL). Support for this work was also provided by
Bench-to-Bedside awards from the NIH Clinical Center and Office of Rare
Diseases. Research was supported in part by a grant from the National
Niemann-Pick Disease Foundation to SMC. NMY was supported by the Ara
Parseghian Medical Research Foundation (APMRF). APMRF also supported the
collection of control CSF samples which were facilitated by the efforts
of Dr. Cyndi Tifft. The authors would also like to acknowledge the
contribution of the caretakers, the patients and their families, who
participated in this study.
NR 53
TC 17
Z9 17
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
EI 1573-2665
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD JAN
PY 2014
VL 37
IS 1
BP 83
EP 92
DI 10.1007/s10545-013-9610-6
PG 10
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 281KN
UT WOS:000329100200011
PM 23653225
ER
PT J
AU Stark, AR
Carlo, WA
Vohr, BR
Papile, LA
Saha, S
Bauer, CR
Oh, W
Shankaran, S
Tyson, JE
Wright, LL
Poole, WK
Das, A
Stoll, BJ
Fanaroff, AA
Korones, SB
Ehrenkranz, RA
Stevenson, DK
Peralta-Carcelen, M
Wilson-Costello, DE
Bada, HS
Heyne, RJ
Johnson, YR
Lee, KG
Steichen, JJ
AF Stark, Ann R.
Carlo, Waldemar A.
Vohr, Betty R.
Papile, Lu Ann
Saha, Shampa
Bauer, Charles R.
Oh, William
Shankaran, Seetha
Tyson, Jon E.
Wright, Linda L.
Poole, W. Kenneth
Das, Abhik
Stoll, Barbara J.
Fanaroff, Avroy A.
Korones, Sheldon B.
Ehrenkranz, Richard A.
Stevenson, David K.
Peralta-Carcelen, Myriam
Wilson-Costello, Deanne E.
Bada, Henrietta S.
Heyne, Roy J.
Johnson, Yvette R.
Lee, Kimberly Gronsman
Steichen, Jean J.
CA Eunice Kennedy Shriver Natl Inst
TI Death or Neurodevelopmental Impairment at 18 to 22 Months Corrected Age
in a Randomized Trial of Early Dexamethasone to Prevent Death or Chronic
Lung Disease in Extremely Low Birth Weight Infants
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID LOW-DOSE DEXAMETHASONE; PRETERM INFANTS; FOLLOW-UP; BRONCHOPULMONARY
DYSPLASIA; PHYSICAL GROWTH; CEREBRAL-PALSY; RISK; THERAPY;
CORTICOSTEROIDS; PHARMACOKINETICS
AB Objective To evaluate the incidence of death or neurodevelopmental impairment (NDI) at 18-22 months corrected age in subjects enrolled in a trial of early dexamethasone treatment to prevent death or chronic lung disease in extremely low birth weight infants.
Study design Evaluation of infants at 18-22 months corrected age included anthropomorphic measurements, a standard neurological examination, and the Bayley Scales of Infant Development-II, including the Mental Developmental Index and the Psychomotor Developmental Index. NDI was defined as moderate or severe cerebral palsy, Mental Developmental Index or Psychomotor Developmental Index <70, blindness, or hearing impairment.
Results Death or NDI at 18-22 months corrected age was similar in the dexamethasone and placebo groups (65% vs 66%, P = .99 among those with known outcome). The proportion of survivors with NDI was also similar, as were mean values for weight, length, and head circumference and the proportion of infants with poor growth (50% vs 41%, P = .42 for weight less than 10th percentile); 49% of infants in the placebo group received treatment with corticosteroid compared with 32% in the dexamethasone group (P = .02).
Conclusion The risk of death or NDI and rate of poor growth were high but similar in the dexamethasone and placebo groups. The lack of a discernible effect of early dexamethasone on neurodevelopmental outcome may be due to frequent clinical corticosteroid use in the placebo group.
C1 [Stark, Ann R.] Vanderbilt Univ, Sch Med, Div Neonatol, Nashville, TN 37212 USA.
[Carlo, Waldemar A.; Peralta-Carcelen, Myriam] Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA.
[Vohr, Betty R.; Oh, William] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Papile, Lu Ann] Indiana Univ Sch Med, Div Neonatol, Indianapolis, IN 46202 USA.
[Saha, Shampa; Poole, W. Kenneth] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Bauer, Charles R.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Steichen, Jean J.] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45229 USA.
[Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Tyson, Jon E.] Univ Texas Hlth Sci Ctr Houston, Dept Pediat, Houston, TX 77030 USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Fanaroff, Avroy A.; Wilson-Costello, Deanne E.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Korones, Sheldon B.; Bada, Henrietta S.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Stevenson, David K.] Stanford Univ, Sch Med, Div Neonatal & Dev Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Stevenson, David K.] Lucille Packard Childrens Hosp, Palo Alto, CA USA.
[Heyne, Roy J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Johnson, Yvette R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Lee, Kimberly Gronsman] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA.
RP Stark, AR (reprint author), Monroe Carell Jr Childrens Hosp Vanderbilt, Div Neonatol, 2200 Childrens Way,DOT 11111, Nashville, TN 37232 USA.
EM ann.r.stark@vanderbilt.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development Cooperative Multicenter Neonatal Research Network; General
Clinical Research Centers Program
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development Cooperative Multicenter Neonatal
Research Network and the General Clinical Research Centers Program. Data
collected at participating sites of the National Institute of Child
Health and Human Development Neonatal Research Network were transmitted
to RTI International, the data coordinating center for the network,
which stored, managed, and analyzed the data for this study. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health. The
authors declare no conflicts of interest.
NR 30
TC 8
Z9 9
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JAN
PY 2014
VL 164
IS 1
BP 34
EP +
DI 10.1016/j.jpeds.2013.07.027
PG 8
WC Pediatrics
SC Pediatrics
GA 276FU
UT WOS:000328734700009
PM 23992673
ER
PT J
AU Wadhawan, R
Oh, W
Hintz, SR
Blakely, ML
Das, A
Bell, EF
Saha, S
Laptook, AR
Shankaran, S
Stoll, BJ
Walsh, MC
Higgins, RD
AF Wadhawan, R.
Oh, W.
Hintz, S. R.
Blakely, M. L.
Das, A.
Bell, E. F.
Saha, S.
Laptook, A. R.
Shankaran, S.
Stoll, B. J.
Walsh, M. C.
Higgins, R. D.
CA NICHD Neonatal Res Network
TI Neurodevelopmental outcomes of extremely low birth weight infants with
spontaneous intestinal perforation or surgical necrotizing enterocolitis
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE spontaneous intestinal perforation; necrotizing enterocolitis; extremely
low birth weight; neurodevelopmental impairment
ID NEONATAL-RESEARCH-NETWORK; PERITONEAL DRAINAGE; PREMATURE-INFANTS;
GROWTH; LAPAROTOMY; AGE; INDOMETHACIN; ASSOCIATION; CHILDREN; SURGERY
AB OBJECTIVE: To determine if extremely low birth weight infants with surgical necrotizing enterocolitis have a higher risk of death or neurodevelopmental impairment and neurodevelopmental impairment among survivors (secondary outcome) at 18-22 months corrected age compared with infants with spontaneous intestinal perforation and infants without necrotizing enterocolitis or spontaneous intestinal perforation.
STUDY DESIGN: Retrospective analysis of the Neonatal Research Network very low birth weight registry, evaluating extremely low birth weight infants born between 2000 and 2005. The study infants were designated into three groups: (1) spontaneous intestinal perforation without necrotizing enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3) neither spontaneous intestinal perforation nor necrotizing enterocolitis. Multivariate logistic regression analysis was performed to evaluate the association between the clinical group and death or neurodevelopmental impairment, controlling for multiple confounding factors including center.
RESULT: Infants with surgical necrotizing enterocolitis had the highest rate of death before hospital discharge (53.5%) and death or neurodevelopmental impairment (82.3%) compared with infants in the spontaneous intestinal perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar results were observed for neurodevelopmental impairment among survivors. On logistic regression analysis, both spontaneous intestinal perforation and surgical necrotizing enterocolitis were associated with increased risk of death or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2 and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively).
CONCLUSION: Spontaneous intestinal perforation and surgical necrotizing enterocolitis are associated with a similar increase in the risk of death or neurodevelopmental impairment and neurodevelopmental impairment among extremely low birth weight survivors at 18-22 months corrected age.
C1 [Wadhawan, R.; Oh, W.; Laptook, A. R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Hintz, S. R.] Stanford Univ, Sch Med, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA.
[Blakely, M. L.] Vanderbilt Univ, Dept Pediat Surg, Nashville, TN 37235 USA.
[Das, A.] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Bell, E. F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Saha, S.] RTI Int, Stat & Epidemiol Unit, Durham, NC USA.
[Shankaran, S.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Stoll, B. J.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
[Walsh, M. C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Higgins, R. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Wadhawan, R (reprint author), Florida Hosp Children, Ctr Neonatal Care, 2501 N Orange Ave,Suite 446, Orlando, FL 32804 USA.
EM rajan.wadhawan.md@flhosp.org
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's Generic
Database Study and Follow-up Study. Data collected at participating
sites of the NICHD Neonatal Research Network (NRN) were transmitted to
RTI International, the data coordinating center (DCC) for the network,
which stored, managed and analyzed the data for this study. On behalf of
the NRN, Drs Abhik Das (DCC Principal Investigator) and Shampa Saha (DCC
Statistician) had full access to all the data in the study and take
responsibility for the integrity of the data and accuracy of the data
analysis. We are indebted to our medical and nursing colleagues. The
following investigators, in addition to those listed as authors,
participated in this study. NRN Steering Committee Chairs-Alan H Jobe,
MD PhD, University of Cincinnati (2000-2006); Michael S Caplan, MD,
University of Chicago, Pritzker School of Medicine (2006-present).
Alpert Medical School of Brown University and Women & Infants Hospital
of Rhode Island (U10 HD27904)-Betty R Vohr, MD; Bonnie E Stephens, MD;
Angelita M Hensman, RN BSN; Barbara Alksninis, PNP; Bill Cashore, MD;
Theresa M Leach, MEd CAES; Martha R Leonard, BA BS; Kalida Mehta; Lucy
Noel; Suzy Ventura; Victoria E Watson, MS CAS. Case Western Reserve
University, Rainbow Babies & Children's Hospital (U10 HD21364, M01
RR80)-Avroy A Fanaroff, MD; Deanne E Wilson-Costello, MD; Nancy S
Newman, RN; Bonnie S Siner, RN. Cincinnati Children's Hospital Medical
Center, University of Cincinnati Hospital and Good Samaritan Hospital
(U10 HD27853, M01 RR8084)-Kurt Schibler, MD; Edward F Donovan, MD; Jean
J Steichen, MD; Kimberly Yolton, PhD; Kate Bridges, MD; Barbara
Alexander, RN; Teresa L Gratton, PA; Cathy Grisby, BSN CCRC; Marcia
Worley Mersmann, RN CCRC; Holly L. Mincey, RN BSN; Jody Hessling, RN.
Duke University School of Medicine, University Hospital and Durham
Regional Hospital (U10 HD40492, M01 RR30)-Ronald N Goldberg, MD; Ricki F
Goldstein, MD; C Michael Cotten, MD MHS; Kimberley A Fisher, PhD FNP-BC
IBCLC; Kathryn E Gustafson, PhD; Melody B Lohmeyer, RN MSN. Emory
University, Children's Healthcare of Atlanta, Grady Memorial Hospital
and Emory Crawford Long Hospital (U10 HD27851, M01 RR39)-David P
Carlton, MD; Ira Adams-Chapman, MD; Linda Black; Ann M Blackwelder, RNC
BS MS; Sheena Carter, PhD; Elisabeth Dinkins, PNP; Ellen C Hale, RN BS
CCRC; Judson Miller, MD; Maureen Mulligan LaRossa, RN; Irma Seabrook,
RRT; Gloria V Smikle, PNP MSN. Eunice Kennedy Shriver National Institute
of Child Health and Human Development-Linda L Wright, MD; Elizabeth M
McClure, MEd; Stephanie Archer, MA. Indiana University, University
Hospital, Methodist Hospital, Riley Hospital for Children and Wishard
Health Services (U10 HD27856, M01 RR750-Brenda B Poindexter, MD MS;
James A Lemons, MD; Ann B Cook, MS; Anna M Dusick, MD FAAP; Dianne E
Herron, RN; Lucy C Miller, RN BSN CCRC; Heike M Minnich, PsyD HSPP;
Leslie Richard, RN; Leslie Dawn Wilson, BSN CCRC; Faithe Hamer, BS. RTI
International (U10 HD36790)-W Kenneth Poole, PhD; Betty K Hastings;
Elizabeth M McClure, MEd; Margaret Cunningham, BS; Jeanette O'Donnell
Auman, BS; Jamie E Newman, PhD MPH; Carolyn Petrie Huitema, MS; Kristin
M Zaterka-Baxter, RN BSN.; Stanford University, El Camino Hospital and
Lucile Packard Children's Hospital (U10 HD27880, M01 RR70)-Krisa P Van
Meurs, MD; David K Stevenson, MD; Marian M Adams, MD; M Bethany Ball, BS
CCRC, Joan M Baran, PhD; Ginger K Brudos, PhD; Anne M DeBattista, RN
PNP; Dharshi Sivakumar, MD MRCP; Nicholas H St. John, PhD. University of
Alabama at Birmingham Health System and Children's Hospital of Alabama
(U10 HD34216, M01 RR32)-Waldemar A Carlo, MD; Namasivayam Ambalavanan,
MD; Myriam Peralta-Carcelen, MD MPH; Amanda Soong, MD; Monica V Collins,
RN BSN MaEd; Shirley S Cosby, RN BSN; Kirstin J Bailey, PhD; Fred J
Biasini, PhD; Stephanie A Chopko, PhD; Mary Beth Moses, PT MS PCS;
Kathleen G Nelson, MD; Vivien A Phillips, RN BSN; Julie Preskitt, MSOT
MPH; Richard V Rector, PhD; Sally Whitley, MA OTR-L FAOTA. University of
California-San Diego Medical Center and Sharp Mary Birch Hospital for
Women and Newborns (U10 HD40461)-Neil N Finer, MD; Paul R Wozniak, MD;
Maynard R Rasmussen, MD; Yvonne E Vaucher, MD MPH; Kathy Arnell, RNC;
Clarence Demetrio, RN; Chris Henderson, RCP CRTT; Wade Rich, BSHS RRT;
Rene Barbieri-Welge; Ayala Ben-Tall; Martha G Fuller, RN MSN; Elaine
Ito; Meghan Lukasik; Deborah Pontillo; Donna Posin, OTR/L MPA; Cheryl
Runyan; James Wilkes. University of Miami Holtz Children's Hospital (U10
HD21397, M01 RR16587)-Shahnaz Duara, MD; Charles R Bauer, MD; Ruth
Everett-Thomas, RN MSN; Mary Allison, RN; Maria Calejo, MS; Alexis N
Diaz, BA; Silvia M Frade Eguaras, MA; Yamiley C Gideon, BA; Kasey
Hamlin-Smith, PhD; Sylvia Hiriart-Fajardo, MD; Lisa Jean-Gilles, BA; Ann
Londono, MD; Elaine O Mathews, RN. University of New Mexico Health
Sciences Center (U10 HD53089, M01 RR997)-Kristi L Watterberg, MD; Lu-Ann
Papile, MD; Janell Fuller, MD Conra Backstrom Lacy, RN; Debra V Long,
BSN; Jean Lowe, PhD; Rebecca Montman, BSN; Julie Rohr, MSN RNC CNS.
University of Rochester Medical Center, Golisano Children's Hospital
(U10 HD40521, M01 RR44)-Dale L Phelps, MD; Gary J Myers, MD; Linda J
Reubens, RN CCRC; Erica Burnell, RN; Julie Babish Johnson, MSW; Diane
Hust, MS RN CS; Rosemary L Jensen; Emily Kushner, MA; Joan Merzbach,
LMSW; Kelley Yost, PhD. University of Tennessee (U10 HD21415)-Sheldon B
Korones, MD; Henrietta S Bada, MD; Tina Hudson, RN BSN; Marilyn
Williams, LCSW; Kimberly Yolton, PhD. University of Texas Southwestern
Medical Center at Dallas, Parkland Health & Hospital System and
Children's Medical Center Dallas (U10 HD40689, M01 RR633)-Pablo J
Sanchez, MD; Charles R Rosenfeld, MD; Walid A Salhab, MD; R Sue Broyles,
MD; Roy J Heyne, MD; Sally S Adams, MS RN CPNP; Cristin Dooley, MS LSSP;
Gaynelle Hensley, RN; Elizabeth Heyne, PA-C; Jackie F Hickman, RN; Linda
A Madden, BSN RN CPNP; Susie Madison, RN; Nancy A Miller, RN; Janet S
Morgan, RN; Alicia Guzman; Catherine Twell Boatman, MS. University of
Texas Health Science Center at Houston Medical School, Children's
Memorial Hermann Hospital and Lyndon Baines Johnson General
Hospital/Harris County Hospital District (U10 HD21373)-Kathleen A
Kennedy, MD MPH; Jon E Tyson, MD MPH; Pamela J Bradt, MD MPH; Patricia W
Evans, MD; Esther G Akpa, RN BSN; Nora Alaniz, BS; Patty A Cluff, RN;
Susan Dieterich, PhD; Claudia I Franco, RNC MSN; Anna E Lis, RN BSN;
Terri Major-Kincade, MD MPH; Georgia E McDavid, RN; Brenda H Morris, MD;
Maegan C Simmons, RN; Patti Pierce Tate, RCP; Stacey Reddoch, BA; Laura
L Whitely, MD; Sharon Wright, MT.; Wake Forest University, Baptist
Medical Center, Forsyth Medical Center, and Brenner Children's Hospital
(GCRC M01 RR7122, U10 HD40498)-T Michael O'Shea, MD MPH; Robert G
Dillard, MD; Nancy J Peters, RN CCRP; Korinne Chiu, MA; Deborah Evans
Allred, MA LPA; Donald J Goldstein, PhD; Raquel Halfond, MA; Barbara G
Jackson, RN BSN; Carroll Peterson, MA; Ellen L Waldrep, MS; Melissa
Whalen Morris, MA; Gail Wiley Hounshell, PhD. Wayne State University,
Hutzel Women's Hospital and Children's Hospital of Michigan (U10
HD21385)-Virginia Delaney-Black, MD MPH; Yvette R Johnson, MD MPH;
Rebecca Bara, RN BSN; Geraldine Muran, RN BSN; Deborah Kennedy, RN BSN;
Laura Goldston, MA. Yale University Yale-New Haven Children's Hospital
(U10 HD27871, M01 RR125, M01 RR6022, UL1 RR24139)-Richard A Ehrenkranz,
MD; Patricia Gettner, RN; Monica Konstantino, RN BSN; JoAnn Poulsen, RN;
Janet Taft, RN BSN; Nancy Close, PhD; Elaine Romano, MSN; Joanne
Poulsen, RN.
NR 29
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Z9 22
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
EI 1476-5543
J9 J PERINATOL
JI J. Perinatol.
PD JAN
PY 2014
VL 34
IS 1
BP 64
EP 70
DI 10.1038/jp.2013.128
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 281TD
UT WOS:000329123000013
PM 24135709
ER
PT J
AU Alves, G
Ogurtsov, AY
Yu, YK
AF Alves, Gelio
Ogurtsov, Aleksey Y.
Yu, Yi-Kuo
TI Molecular Isotopic Distribution Analysis (MIDAs) with Adjustable Mass
Accuracy
SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
LA English
DT Article
DE Isotopic Distribution; Accurate mass; Mass spectrometry; Proteomics
ID FOURIER-TRANSFORM; EFFICIENT CALCULATION; PEAK DISTRIBUTIONS;
RESOLUTION; SPECTROMETRY; PROTEINS; SPECTRA; ALGORITHM; PEPTIDES;
FORMULAS
AB In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html
.
C1 [Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM yyu@ncbi.nlm.nih.gov
FU Intramural Research Program of the National Library of Medicine at the
National Institutes of Health; National Institutes of Health
FX The authors thank Alfred Yergey for sending them the NeutronCluster
code, and Alan Rockwood for providing them with codes of Mercury, Emass,
Qmass, and Mercury5. The authors thank the administrative group of the
National Institutes of Health Biowulf Clusters, where all the
computational tasks were carried out. They also thank the National
Institutes of Health Fellows Editorial Board for editorial assistance.
This work was supported by the Intramural Research Program of the
National Library of Medicine at the National Institutes of Health.
Funding for Open Access publication charges for this article was
provided by the National Institutes of Health.
NR 44
TC 1
Z9 1
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1044-0305
EI 1879-1123
J9 J AM SOC MASS SPECTR
JI J. Am. Soc. Mass Spectrom.
PD JAN
PY 2014
VL 25
IS 1
BP 57
EP 70
DI 10.1007/s13361-013-0733-7
PG 14
WC Biochemical Research Methods; Chemistry, Analytical; Chemistry,
Physical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 283IL
UT WOS:000329239600008
PM 24254576
ER
PT J
AU Delling, FN
Gona, P
Larson, MG
Lehman, B
Manning, WJ
Levine, RA
Benjamin, EJ
Vasan, RS
AF Delling, Francesca N.
Gona, Philimon
Larson, Martin G.
Lehman, Birgitta
Manning, Warren J.
Levine, Robert A.
Benjamin, Emelia J.
Vasan, Ramachandran S.
TI Mild Expression of Mitral Valve Prolapse in the Framingham Offspring:
Expanding the Phenotypic Spectrum
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Mitral valve prolapse; Echocardiography
ID TERM FOLLOW-UP; NATURAL-HISTORY; AORTIC-ANEURYSM; MARFAN-SYNDROME; VENA
CONTRACTA; REGURGITATION; DIAGNOSIS; SEVERITY; LOCUS; RECONSTRUCTION
AB Background: Mitral valve (MV) prolapse (MVP) is a common disorder associated with mitral regurgitation, endocarditis, heart failure, and sudden death. Nondiagnostic morphologies have been described in the familial context and may represent early expression of MVP in those genetically predisposed. The aim of this study was to explore the spectrum of MVP abnormalities in the community and compare their clinical and echocardiographic features.
Methods: We measured annular diameter MV leaflet displacement, thickness, anterior and posterior leaflet projections onto the annulus, MV leaflet coaptation height (posterior MV leaflet projection/annular diameter), and MR jet height in 296 individuals of the Framingham Offspring Study with MVP (n = 77), the "abnormal anterior coaptation" (AAC) phenotype (n = 11) or "minimal systolic displacement" (MSD) (n = 57), and 151 age-matched and sex-matched referents with no MVP or its nondiagnostic forms.
Results: AAC did not meet diagnostic displacement criteria but resembled MVP with regard to annular diameter and leaflet thickness (P > .05 for both). AAC was similar to posterior MVP with regard to posterior leaflet asymmetry and an anteriorly shifted coaptation (P = .91). Compared to patients with MSD and referents, patients with AAC had greater leaflet coaptation height, thickness, and annular diameter (P < .05 for all). MSD shared the posterior leaflet asymmetry with MVP, but the coaptation point was more posterior (coaptation height = 31% vs. 42%, P < .0001), as seen in referents. A higher proportion of patients with MVP had jet height >= 2 mm (mild or greater MR) compared with the other participants (44% vs. 16%, P < .0001).
Conclusions: Nondiagnostic morphologies are observed in the community and share the common feature of posterior leaflet asymmetry with MVP. AAC and MSD may thus represent early expressions of MVP. Longitudinal studies are warranted to elucidate the natural history of these phenotypes.
C1 [Delling, Francesca N.; Gona, Philimon; Larson, Martin G.; Lehman, Birgitta; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Delling, Francesca N.; Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02215 USA.
[Gona, Philimon] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Larson, Martin G.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Levine, Robert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Dept Med, Boston, MA USA.
RP Delling, FN (reprint author), Beth Israel Deaconess Med Ctr, Cardiovasc Div, E-SH-458,330 Brookline Ave, Boston, MA 02215 USA.
EM fdelling@bidmc.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
Emelia/0000-0003-4076-2336
FU Founders Affiliate American Heart Association Clinical Research Program;
National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, R01HL080124, RO1HL0107385]
FX This work was supported by the Founders Affiliate American Heart
Association Clinical Research Program (Dr Delling) and by the National
Heart, Lung, and Blood Institute's Framingham Heart Study (Contract No.
N01-HC-25195), R01HL080124, and RO1HL0107385 (Dr Vasan).
NR 39
TC 6
Z9 6
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD JAN
PY 2014
VL 27
IS 1
BP 17
EP 23
DI 10.1016/j.echo.2013.09.015
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 281PN
UT WOS:000329113600005
PM 24206636
ER
PT J
AU Wang, RX
Xiao, YL
Taubenberger, JK
AF Wang, Ruixue
Xiao, Yongli
Taubenberger, Jeffery K.
TI Rapid sequencing of influenza A virus vRNA, cRNA and mRNA non-coding
regions
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE Influenza A virus; Noncoding regions; RACE (random amplification of cDNA
ends)
ID TRANSCRIPTION; POLYMERASE; REPLICATION; AMPLIFICATION; ENDONUCLEASE;
NUCLEOTIDE; SEGMENTS; INITIATION; EVOLUTION; PROTEIN
AB Characterizing the genomic sequences of influenza A viruses is important for pathophysiological and evolutionary studies. Noncoding regions (NCR) of influenza A virus have been shown to play critical roles in replication and transcription but their sequences are infrequently determined. In this study, a method employing poly(A) addition and SMART (switching mechanism at 5' end of RNA transcript) technology is described for directly determining and discriminating both NCR ends of viral RNA (vRNA), complementary RNA (cRNA), or NCR and cap sequences from viral mRNA. This modified method may also be used to characterize the NCRs of influenza A virus samples in which the RNA has been degraded. Published by Elsevier B.V.
C1 [Wang, Ruixue; Xiao, Yongli; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,Room 3E19A-2,MSC 3203, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
FU NIAID
FX This work was supported by the Intramural Research Program of NIAID.
NR 31
TC 3
Z9 3
U1 0
U2 13
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 2014
VL 195
BP 26
EP 33
DI 10.1016/j.jviromet.2013.09.005
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 277FQ
UT WOS:000328804800004
PM 24096269
ER
PT J
AU Negrete, A
Pai, A
Shiloach, J
AF Negrete, Alejandro
Pai, Amrita
Shiloach, Joseph
TI Use of hollow fiber tangential flow filtration for the recovery and
concentration of HIV virus-like particles produced in insect cells
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE Virus-like particles; Recovery; Concentration; Insect cells; Hollow
fiber; Tangential flow filtration
ID ULTRAFILTRATION; PURIFICATION; MICROFILTRATION; TECHNOLOGY; VACCINES;
VECTORS; CULTURE; SYSTEMS; PROTEIN; WATER
AB Attenuated viruses, inactivated viruses and virus like particles (VLPs) are known to be efficient vaccines partially due to their particulate structure. A potential HIV vaccine candidate engineered as a VLP (HIV gag-VLP) and produced in insect cells is currently under preclinical trials demanding large amounts. Due to their extreme fragility and sensitivity to shear forces the recovery and concentration of these extracellular enveloped particles of approximately 120 nm in size is challenging. The current bench scale gradient ultracentrifugation and precipitation methods have been found unsuitable for larger scale processes. In this study a two-step tangential flow filtration (TFF) process using hollow fibers was developed for the clarification and concentration of HIV gag-VLPs. The first step is microfiltration for cell removal and the second step is ultrafiltration for concentrating the HIV gag-VLPs. The chosen parameters for the microfiltration step were hollow fiber membranes of 0.45 mu m cut off 5000 s(-1) shear force and a flux of 10 LMH. The chosen parameters for the ultrafiltration step were a 500 kDa cut off membrane, 6000 s(-1) shear force and a trans-membrane pressure (TMP) of 1.25 bar. The utilization of these parameters provided with concentrated HIV-gag VLPs from 2 L of starting cell suspension within 6 h of processing time. These downstream processing conditions are extremely valuable for the further large-scale purification process development for-HIV gag-VLPs and other particulate bioproducts. Published by Elsevier B.V.
C1 [Negrete, Alejandro; Pai, Amrita; Shiloach, Joseph] Natl Inst Diabet & Digest & Kidney Dis, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Pai, Amrita] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
RP Negrete, A (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Biotechnol Core Lab, NIH, 14 Serv Rd West,Bldg 14A Room 173 MS 5522, Bethesda, MD 20892 USA.
EM negretea@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX The authors would like to thank Mr. Russell A. Vassell for his help with
the Western Blot analysis, Dr. Prasad Vennakalanti for the negative
stain TEM analysis, Dr. Carol Weiss for critically reviewing this
manuscript, and MPH Christopher McClure and Mrs. D. Livnat for critical
editorial assistance. Funding was provided by the Intramural program at
the National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 20
TC 8
Z9 10
U1 5
U2 32
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 2014
VL 195
BP 240
EP 246
DI 10.1016/j.jviromet.2013.10.017
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 277FQ
UT WOS:000328804800034
PM 24157258
ER
PT J
AU Nakamura, T
Ito, T
Uchida, M
Hijioka, M
Igarashi, H
Oono, T
Kato, M
Nakamura, K
Suzuki, K
Jensen, RT
Takayanagi, R
AF Nakamura, Taichi
Ito, Tetsuhide
Uchida, Masahiko
Hijioka, Masayuki
Igarashi, Hisato
Oono, Takamasa
Kato, Masaki
Nakamura, Kazuhiko
Suzuki, Koichi
Jensen, Robert T.
Takayanagi, Ryoichi
TI PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic
pancreatitis and effect of their activation by a GLP-1R agonist
SO LABORATORY INVESTIGATION
LA English
DT Article
DE diabetes mellitus; glucagon-like peptide-1; GLP-1 receptor; liraglutide;
pancreatic stellate cells; pancreatitis; proliferation
ID GLUCAGON-LIKE PEPTIDE-1; STELLATE CELLS; ANGIOTENSIN-II; RECEPTOR
ACTIVATION; COLLAGEN PRODUCTION; SIGNALING PATHWAYS; ENDOCRINE PANCREAS;
INCRETIN THERAPY; PROTEIN-KINASES; GENE-EXPRESSION
AB There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic beta cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation/chronic activation of PSCs, which may lead to important effects in the pancreas.
C1 [Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Takayanagi, Ryoichi] Kyushu Univ, Dept Med & Bioregulatory Sci, Fukuoka 8128582, Japan.
[Nakamura, Taichi; Jensen, Robert T.] NIDDK, Dept Cell Biol Sect, NIH, Bethesda, MD 20892 USA.
[Suzuki, Koichi] Natl Inst Infect Dis, Dept Leprosy Res Ctr, Tokyo, Japan.
RP Ito, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM itopapa@intmed3.med.kyushu-u.ac.jp
RI U-ID, Kyushu/C-5291-2016
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan
[20590808]; Ministry of Health, Labour, and Welfare Japan [50253448];
intramural research funds of NIDDK, NIH
FX We appreciate the technical support from the Research Support Center,
Graduate School of Medical Sciences, Kyushu University and partial
support from intramural research funds of NIDDK, NIH. This work was
supported by a grant from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan (20590808, T Ito) and the Research
Committee provided by the Ministry of Health, Labour, and Welfare Japan
(50253448, T Ito).
NR 81
TC 9
Z9 9
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD JAN
PY 2014
VL 94
IS 1
BP 63
EP 78
DI 10.1038/labinvest.2013.133
PG 16
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 282MF
UT WOS:000329175200006
PM 24217090
ER
PT J
AU Patel, N
Jankovic, J
Hallett, M
AF Patel, Neepa
Jankovic, Joseph
Hallett, Mark
TI Sensory aspects of movement disorders
SO LANCET NEUROLOGY
LA English
DT Review
ID RESTLESS LEGS SYNDROME; FOCAL HAND DYSTONIA; REGIONAL PAIN SYNDROME;
PARKINSONS-DISEASE PATIENTS; VIBRATION-INDUCED ILLUSION; DEEP
BRAIN-STIMULATION; TACTILE TEMPORAL DISCRIMINATION; PRIMARY
SOMATOSENSORY CORTEX; PRIMARY TORSION DYSTONIA; LA-TOURETTES-SYNDROME
AB Movement disorders, which include disorders such as Parkinson's disease, dystonia, Tourette's syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed.
C1 [Patel, Neepa; Jankovic, Joseph] Baylor Coll Med, Parkinsons Dis Ctr, Houston, TX 77030 USA.
[Patel, Neepa; Jankovic, Joseph] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Jankovic, J (reprint author), Baylor Coll Med, Parkinsons Dis Ctr, 6550 Fannin,Suite 1801, Houston, TX 77030 USA.
EM josephj@bcm.edu
FU National Parkinson Foundation; Huntington Disease Association of
America; Dystonia Medical Research Foundation
FX MH is an employee of the National Institutes of Health. JJ acknowledges
the support of the National Parkinson Foundation and the Huntington
Disease Association of America. NP has received support for a movement
disorder fellowship from the Dystonia Medical Research Foundation.
NR 214
TC 53
Z9 56
U1 6
U2 37
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD JAN
PY 2014
VL 13
IS 1
BP 100
EP 112
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 280AL
UT WOS:000329000900021
PM 24331796
ER
PT J
AU Chung, YJ
Robert, C
Gough, SM
Rassool, FV
Aplan, PD
AF Chung, Yang Jo
Robert, Carine
Gough, Sheryl M.
Rassool, Feyruz V.
Aplan, Peter D.
TI Oxidative stress leads to increased mutation frequency in a murine model
of myelodysplastic syndrome
SO LEUKEMIA RESEARCH
LA English
DT Article
DE MDS; AML; ROS; Mutation; NHD13; Big Blue (R) mice
ID CELL-CYCLE CHECKPOINTS; ACUTE MYELOID-LEUKEMIA; DNA-DAMAGE;
HYDROGEN-PEROXIDE; MOUSE MODEL; REPAIR; INDUCTION; CANCER;
DIFFERENTIATION; INSTABILITY
AB The myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML). Although it has been suggested that additional mutations lead to progression of MDS to AML, the causative agent(s) for such mutations remains unclear. Oxidative stress is a potential cause, therefore, we evaluated levels of reactive oxygen species (ROS) in NUP98-HOXD13 (NHD13) transgenic mice, a murine model for MDS. Increased levels of ROS were detected in bone marrow nucleated cells (BMNC) that express CD71, a marker for cell proliferation, as well as immature, lineage negative bone marrow nucleated cells from NHD13 mice. In addition to the increase in ROS, increased DNA double strand breaks and activation of a G2/M phase cell cycle checkpoint were noted in NHD13 BMNC. Finally, using an in vivo assay for mutation frequency, we detected an increased mutation frequency in NHD13 BMNC. These results suggest that oxidative stress may contribute to disease progression of MDS to AML through ineffective repair of DNA damage and acquisition of oncogenic mutations. Published by Elsevier Ltd.
C1 [Chung, Yang Jo; Gough, Sheryl M.; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Robert, Carine; Rassool, Feyruz V.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA.
[Robert, Carine; Rassool, Feyruz V.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Aplan, PD (reprint author), NCI, Leukemia Biol Sect, Genet Branch, NIH,CCR, 37 Convent Dr,Room 6002B, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Aplan, Peter/K-9064-2016
FU NIH
FX This research was supported by the Intramural Research Program of the
NIH.
NR 50
TC 10
Z9 10
U1 1
U2 6
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 2014
VL 38
IS 1
BP 95
EP 102
DI 10.1016/j.leukres.2013.07.008
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 280VM
UT WOS:000329058900015
PM 23958061
ER
PT J
AU Alvheim, AR
Torstensen, BE
Lin, YH
Lillefosse, HH
Lock, EJ
Madsen, L
Froyland, L
Hibbeln, JR
Malde, MK
AF Alvheim, Anita Royneberg
Torstensen, Bente E.
Lin, Yu Hong
Lillefosse, Haldis Haukas
Lock, Erik-Jan
Madsen, Lise
Froyland, Livar
Hibbeln, Joseph R.
Malde, Marian Kjellevold
TI Dietary Linoleic Acid Elevates the Endocannabinoids 2-AG and Anandamide
and Promotes Weight Gain in Mice Fed a Low Fat Diet
SO LIPIDS
LA English
DT Article
DE Endocannabinoids; Linoleic acid; PUFA; n-6; n-3; Low fat; Obesity
ID ADIPOSE-TISSUE DEVELOPMENT; CORONARY-HEART-DISEASE; CANNABINOID
RECEPTOR; DOCOSAHEXAENOIC ACID; EICOSAPENTAENOIC ACID; ARACHIDONIC-ACID;
RISK-FACTOR; RAT-BRAIN; FISH-OIL; OBESITY
AB Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity. Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA), and we sought to determine if low fat diets (LFD) could be made obesogenic by increasing the endocannabinoid precursor pool of ARA, causing excessive endocannabinoid signaling leading to weight gain and a metabolic profile associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8 en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated plasma leptin, and resulted in larger adipocytes and more macrophage infiltration in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and caused greater weight gain than in an isocaloric reduction to 1 en% LNA. Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and increases the risk of developing obesity. Thus a high dietary content of LNA (8 en%) increases the adipogenic properties of a low fat diet.
C1 [Alvheim, Anita Royneberg; Torstensen, Bente E.; Lillefosse, Haldis Haukas; Lock, Erik-Jan; Madsen, Lise; Froyland, Livar; Malde, Marian Kjellevold] Natl Inst Nutr & Seafood Res NIFES, N-5817 Bergen, Norway.
[Alvheim, Anita Royneberg] Univ Bergen, Dept Biomed, Bergen, Norway.
[Lin, Yu Hong; Hibbeln, Joseph R.] NIAAA, Rockville, MD 20852 USA.
[Lillefosse, Haldis Haukas; Madsen, Lise] Univ Copenhagen, Dept Biol, Copenhagen, Denmark.
RP Malde, MK (reprint author), Natl Inst Nutr & Seafood Res NIFES, POB 2029, N-5817 Bergen, Norway.
EM marian.malde@nifes.no
RI Madsen, Lise/C-6246-2012; Kjellevold, Marian/C-2973-2012
OI Madsen, Lise/0000-0003-4468-1947; Kjellevold, Marian/0000-0001-7070-5784
FU National Institute of Nutrition and Seafood Research (NIFES), Bergen,
Norway; Intramural Research program of the National Institute on Alcohol
Abuse and Alcoholism, NIH, USA; Research Council of Norway [186908/l10]
FX This study was funded by the National Institute of Nutrition and Seafood
Research (NIFES), Bergen, Norway, Intramural Research program of the
National Institute on Alcohol Abuse and Alcoholism, NIH, USA, and the
Research Council of Norway 186908/l10.
NR 57
TC 15
Z9 15
U1 0
U2 6
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0024-4201
EI 1558-9307
J9 LIPIDS
JI Lipids
PD JAN
PY 2014
VL 49
IS 1
BP 59
EP 69
DI 10.1007/s11745-013-3842-y
PG 11
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 283JF
UT WOS:000329241600006
PM 24081493
ER
PT J
AU Prasad, V
AF Prasad, Vinay
TI Regarding Empiricism and Rationalism in Medicine and 2 Medical
Worldviews
SO MAYO CLINIC PROCEEDINGS
LA English
DT Letter
ID CARE
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 7
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0025-6196
EI 1942-5546
J9 MAYO CLIN PROC
JI Mayo Clin. Proc.
PD JAN
PY 2014
VL 89
IS 1
BP 137
EP 137
DI 10.1016/j.mayocp.2013.10.019
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 282IE
UT WOS:000329163600022
PM 24388033
ER
PT J
AU Levine, KE
Han, L
McWilliams, AC
Essader, AS
Amato, KE
Fernando, RA
Browning, DB
Greene, LC
Ensor, DS
Walker, NJ
Robinson, VG
Collins, BJ
AF Levine, Keith E.
Han, Li
McWilliams, Andrea C.
Essader, Amal S.
Amato, Kelly E.
Fernando, Reshan A.
Browning, Donna B.
Greene, Lisa C.
Ensor, David S.
Walker, Nigel J.
Robinson, Veronica G.
Collins, Bradley J.
TI Characterization of an assortment of commercially available multiwalled
carbon nanotubes
SO MICROCHIMICA ACTA
LA English
DT Article
DE Nanomaterials; Nanotoxicology; MWCNT; Characterization
ID IN-VITRO; CYTOTOXICITY; TOXICITY; NANOMATERIALS; NANOTECHNOLOGY;
MESOTHELIOMA; INDUCTION; OXIDATION; QUALITY; TISSUE
AB The objective of this study was to characterize an assortment of as received, commercially available, non-functionalized multiwalled carbon nanotubes (MWCNT) samples (n = 24) using thermogravimetric analysis, energy dispersive X-ray fluorescence spectrometry, high-resolution transmission electron microscopy and scanning electron microscopy. Each sample was assigned to one of six types based on nominal length and diameter. Some of the samples from the product assortment exhibited significant differences in purity and morphology from their nominal values. Variability in the physicochemical properties of MWCNTs may be a significant factor in why many toxicological investigations have findings that are difficult to reproduce. Therefore, it is strongly recommended that investigators studying these materials present characterization information in addition to providing their source.
C1 [Levine, Keith E.; Han, Li; McWilliams, Andrea C.; Essader, Amal S.; Amato, Kelly E.; Fernando, Reshan A.; Browning, Donna B.; Greene, Lisa C.; Ensor, David S.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Walker, Nigel J.; Robinson, Veronica G.; Collins, Bradley J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
RP Levine, KE (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM levine@rti.org
RI Walker, Nigel/D-6583-2012; Geracitano, Laura/E-6926-2013
OI Walker, Nigel/0000-0002-9111-6855;
FU National Institute of Environmental Health Sciences, National Institute
of Health [N01-ES-65554]
FX This analytical work was funded in full by the National Institute of
Environmental Health Sciences, National Institute of Health, Contract
Number: N01-ES-65554.
NR 35
TC 1
Z9 1
U1 0
U2 11
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0026-3672
EI 1436-5073
J9 MICROCHIM ACTA
JI Microchim. Acta
PD JAN
PY 2014
VL 181
IS 1-2
BP 171
EP 179
DI 10.1007/s00604-013-1088-2
PG 9
WC Chemistry, Analytical
SC Chemistry
GA 281KI
UT WOS:000329099700018
ER
PT J
AU Cai, ZY
Jitkaew, S
Zhao, J
Chiang, HC
Choksi, S
Liu, J
Ward, Y
Wu, LG
Liu, ZG
AF Cai, Zhenyu
Jitkaew, Siriporn
Zhao, Jie
Chiang, Hsueh-Cheng
Choksi, Swati
Liu, Jie
Ward, Yvona
Wu, Ling-gang
Liu, Zheng-Gang
TI Plasma membrane translocation of trimerized MLKL protein is required for
TNF-induced necroptosis
SO NATURE CELL BIOLOGY
LA English
DT Article
ID NONAPOPTOTIC CELL-DEATH; MIXED LINEAGE KINASE; PROGRAMMED NECROSIS;
NECROTIC DEATH; DOMAIN-LIKE; INFLAMMATION; APOPTOSIS; TRPM7; RIP3;
DOWNSTREAM
AB The mixed lineage kinase domain-like protein (MLKL) has recently been identified as a key RIP3 (receptor interacting protein 3) downstream component of tumour necrosis factor (TNF)-induced necroptosis. MLKL is phosphorylated by RIP3 and is recruited to the necrosome through its interaction with RIP3. However, it is still unknown how MLKL mediates TNF-induced necroptosis. Here, we report that MLKL forms a homotrimer through its amino-terminal coiled-coil domain and locates to the cell plasma membrane during TNF-induced necroptosis. By generating different MLKL mutants, we demonstrated that the plasma membrane localization of trimerized MLKL is critical for mediating necroptosis. Importantly, we found that the membrane localization of MLKL is essential for Ca2+ influx, which is an early event of TNF-induced necroptosis. Furthermore, we identified that TRPM7 (transient receptor potential melastatin related 7) is a MLKL downstream target for the mediation of Ca2+ influx and TNF-induced necroptosis. Hence, our study reveals a crucial mechanism of MLKL-mediated TNF-induced necroptosis.
C1 [Cai, Zhenyu; Jitkaew, Siriporn; Zhao, Jie; Choksi, Swati; Ward, Yvona; Liu, Zheng-Gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Chiang, Hsueh-Cheng; Wu, Ling-gang] NINDS, Synapt Transmiss Sect, NIH, Bethesda, MD 20892 USA.
[Liu, Jie] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM zgliu@helix.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX We thank J. Han for MLKL-deficient MEF cells and MLKL antibody, and L.
Looger for GCaMP3 plasmid. This research was supported by the Intramural
Research Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health.
NR 33
TC 215
Z9 223
U1 13
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD JAN
PY 2014
VL 16
IS 1
BP 55
EP +
DI 10.1038/ncb2883
PG 26
WC Cell Biology
SC Cell Biology
GA 280PA
UT WOS:000329042000011
PM 24316671
ER
PT J
AU Chaurasiya, KR
McCauley, MJ
Wang, W
Qualley, DF
Wu, T
Kitamura, S
Geertsema, H
Chan, DSB
Hertz, A
Iwatani, Y
Levin, JG
Musier-Forsyth, K
Rouzina, I
Williams, MC
AF Chaurasiya, Kathy R.
McCauley, Micah J.
Wang, Wei
Qualley, Dominic F.
Wu, Tiyun
Kitamura, Shingo
Geertsema, Hylkje
Chan, Denise S. B.
Hertz, Amber
Iwatani, Yasumasa
Levin, Judith G.
Musier-Forsyth, Karin
Rouzina, Ioulia
Williams, Mark C.
TI Oligomerization transforms human APOBEC3G from an efficient enzyme to a
slowly dissociating nucleic acid-binding protein
SO NATURE CHEMISTRY
LA English
DT Article
ID HIV-1 REVERSE TRANSCRIPTION; CYTIDINE DEAMINASE; LINE-1
RETROTRANSPOSITION; NUCLEOCAPSID PROTEIN; VIF PROTEIN; SOR GENE; DNA;
VIRUS; RESTRICTION; HYPERMUTATION
AB The human APOBEC3 proteins are a family of DNA-editing enzymes that play an important role in the innate immune response against retroviruses and retrotransposons. APOBEC3G is a member of this family that inhibits HIV-1 replication in the absence of the viral infectivity factor Vif. Inhibition of HIV replication occurs by both deamination of viral single-stranded DNA and a deamination-independent mechanism. Efficient deamination requires rapid binding to and dissociation from ssDNA. However, a relatively slow dissociation rate is required for the proposed deaminase-independent roadblock mechanism in which APOBEC3G binds the viral template strand and blocks reverse transcriptase-catalysed DNA elongation. Here, we show that APOBEC3G initially binds ssDNA with rapid on-off rates and subsequently converts to a slowly dissociating mode. In contrast, an oligomerization-deficient APOBEC3G mutant did not exhibit a slow off rate. We propose that catalytically active monomers or dimers slowly oligomerize on the viral genome and inhibit reverse transcription.
C1 [Chaurasiya, Kathy R.; McCauley, Micah J.; Geertsema, Hylkje; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Wang, Wei; Qualley, Dominic F.; Musier-Forsyth, Karin] Ohio State Univ, Ctr Retrovirus Res, Dept Chem & Biochem, Columbus, OH 43210 USA.
[Wang, Wei; Qualley, Dominic F.; Musier-Forsyth, Karin] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
[Wu, Tiyun; Hertz, Amber; Iwatani, Yasumasa; Levin, Judith G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Viral Gene Regulat, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Kitamura, Shingo; Iwatani, Yasumasa] Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi 4600001, Japan.
[Chan, Denise S. B.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA.
[Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA.
RP Chaurasiya, KR (reprint author), Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
EM mark@neu.edu
OI Williams, Mark C./0000-0003-3219-376X
FU National Institutes of Health [GM072462, GM065056]; National Science
Foundation [MCB-1243883]; Japan Society for the Promotion of Science
(JSPS) [KAKENHI_24590568]; NIH Intramural Research Program (NICHD); NSF
IGERT Program [DGE-0504331]
FX The authors thank D. Pollpeter, M.H. Malim and D. Rueda for valuable
discussions, and M.F. Goodman for his generous gift of the F126A/W127A
mutant clone. This work was supported in part by the National Institutes
of Health (GM072462 to M.C.W. and GM065056 to K.M-F.) and the National
Science Foundation (MCB-1243883 to M.C.W.), the Japan Society for the
Promotion of Science (JSPS; KAKENHI_24590568 to Y.I.), and in part by
funds from the NIH Intramural Research Program (NICHD; to J.G.L.).
K.R.C. was supported by the NSF IGERT Program (DGE-0504331).
NR 49
TC 26
Z9 26
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1755-4330
EI 1755-4349
J9 NAT CHEM
JI Nat. Chem.
PD JAN
PY 2014
VL 6
IS 1
BP 28
EP 33
DI 10.1038/NCHEM.1795
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA 279HM
UT WOS:000328951000009
PM 24345943
ER
PT J
AU Waterfall, JJ
Arons, E
Walker, RL
Pineda, M
Roth, L
Killian, JK
Abaan, OD
Davis, SR
Kreitman, RJ
Meltzer, PS
AF Waterfall, Joshua J.
Arons, Evgeny
Walker, Robert L.
Pineda, Marbin
Roth, Laura
Killian, J. Keith
Abaan, Ogan D.
Davis, Sean R.
Kreitman, Robert J.
Meltzer, Paul S.
TI High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing
hairy-cell leukemias
SO NATURE GENETICS
LA English
DT Article
ID BRAF V600E MUTATION; LUNG ADENOCARCINOMA; INHIBITION; MEK
AB To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases.
C1 [Waterfall, Joshua J.; Walker, Robert L.; Pineda, Marbin; Killian, J. Keith; Abaan, Ogan D.; Davis, Sean R.; Meltzer, Paul S.] NCI, Genet Branch, CCR, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
[Arons, Evgeny; Roth, Laura; Kreitman, Robert J.] NCI, Mol Biol Lab, CCR, US NIH, Bethesda, MD 20892 USA.
RP Meltzer, PS (reprint author), NCI, Genet Branch, CCR, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA.
EM pmeltzer@mail.nih.gov
OI Davis, Sean/0000-0002-8991-6458
FU US NIH, NCI, CCR; Hairy Cell Leukemia Research Foundation
FX This work was supported by the Intramural Research Program of the US
NIH, NCI, CCR (P. S. M. and R.J.K.) and the Hairy Cell Leukemia Research
Foundation (R.J.K.).
NR 20
TC 58
Z9 59
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JAN
PY 2014
VL 46
IS 1
BP 8
EP +
DI 10.1038/ng.2828
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 281PM
UT WOS:000329113500005
PM 24241536
ER
PT J
AU Cella, M
Trinchieri, G
AF Cella, Marina
Trinchieri, Giorgio
TI A new VEGF connection between two old neighbors
SO NATURE IMMUNOLOGY
LA English
DT Editorial Material
ID PLASMACYTOID DENDRITIC CELLS; OVARIAN-CANCER; LYMPH-NODE; MICRORNAS;
ANGIOGENESIS; IMMUNITY
C1 [Cella, Marina] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
[Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
RP Cella, M (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA.
EM mcella@pathology.wustl.edu
NR 15
TC 1
Z9 2
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JAN
PY 2014
VL 15
IS 1
BP 8
EP 9
PG 2
WC Immunology
SC Immunology
GA 277DZ
UT WOS:000328800500005
PM 24352317
ER
PT J
AU McFarland, AP
Horner, SM
Jarret, A
Joslyn, RC
Bindewald, E
Shapiro, BA
Delker, DA
Hagedorn, CH
Carrington, M
Gale, M
Savan, R
AF McFarland, Addle P.
Horner, Stacy M.
Jarret, Abigail
Joslyn, Rochelle C.
Bindewald, Eckart
Shapiro, Bruce A.
Delker, Don A.
Hagedorn, Curt H.
Carrington, Mary
Gale, Michael, Jr.
Savan, Ram
TI The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich
elements and hepatitis C virus-induced microRNAs
SO NATURE IMMUNOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; IL28B GENOTYPE; SECONDARY
STRUCTURE; ANTIVIRAL DEFENSES; INTERFERON-LAMBDA; INNATE IMMUNITY;
EXPRESSION; INFECTION; CLEARANCE
AB IFNL3, which encodes interferon-lambda 3 (IFN-lambda 3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance of HCV. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) in the 3' untranslated region (UTR) of IFNL3 mRNA that dictated transcript stability. We found that this polymorphism influenced AU-rich element (ARE)-mediated decay (AMD) of IFNL3 mRNA, as well as the binding of HCV-induced microRNAs during infection. Together these pathways mediated robust repression of the unfavorable IFNL3 polymorphism. Our data reveal a previously unknown mechanism by which HCV attenuates the antiviral response and indicate new potential therapeutic targets for HCV treatment.
C1 [McFarland, Addle P.; Horner, Stacy M.; Jarret, Abigail; Joslyn, Rochelle C.; Gale, Michael, Jr.; Savan, Ram] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Bindewald, Eckart] Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA.
[Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
[Delker, Don A.; Hagedorn, Curt H.] Univ Utah, Sch Med, Div Gastroenterol Hepatol & Nutr, Salt Lake City, UT USA.
[Carrington, Mary] Frederick Natl Lab Canc Res, Sci Applicat Int Corp Frederick, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Carrington, Mary] MIT, Ragon Inst Massachusetts Gen Hosp, Boston, MA USA.
[Carrington, Mary] Harvard Univ, Boston, MA 02115 USA.
RP Savan, R (reprint author), Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
EM savanram@uw.edu
OI Gale, Michael/0000-0002-6332-7436
FU Department of Immunology of the University of Washington; US National
Institutes of Health [AI060389, AI88778, CA148068]; Frederick National
Laboratory for Cancer Research of the US National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the US National
Institutes of Health, Frederick National Laboratory for Cancer Research
and the National Cancer Institute, Center for Cancer Research
FX We thank P. Fink, D. Stetson, E. Clark and C. Lim for critical reading
of the manuscript, and S. Badil and M. Hong for technical assistance.
Supported by the Department of Immunology of the University of
Washington (R.S.), the US National Institutes of Health (AI060389 and
AI88778 to M.G., and CA148068 to C.H.H.) and federal funds from the
Frederick National Laboratory for Cancer Research of the US National
Institutes of Health (HHSN261200800001E) and the Intramural Research
Program of the US National Institutes of Health, Frederick National
Laboratory for Cancer Research and the National Cancer Institute, Center
for Cancer Research (E.B., B.A.S. and M.C.).
NR 45
TC 56
Z9 56
U1 0
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JAN
PY 2014
VL 15
IS 1
BP 72
EP 79
DI 10.1038/ni.2758
PG 8
WC Immunology
SC Immunology
GA 277DZ
UT WOS:000328800500014
PM 24241692
ER
PT J
AU Lucas, CL
Kuehn, HS
Zhao, F
Niemel, JE
Deenick, EK
Palendira, U
Avery, DT
Moens, L
Cannons, JL
Lanai, MB
Stoddard, J
Ouyane, W
Frucht, DM
Rao, VK
Atkinson, TP
Agharahimi, A
Hussey, AA
Folioll, LR
Olivier, KN
Fleisher, TA
Pittaluga, S
Holland, SM
Cohen, JI
Oliveira, JB
Tangye, SG
Schwartzberg, PL
Lenardol, MJ
Uzel, G
AF Lucas, Carrie L.
Kuehn, Hye Sun
Zhao, Fang
Niemel, Julie E.
Deenick, Elissa K.
Palendira, Umaimainthan
Avery, Danielle T.
Moens, Leen
Cannons, Jennifer L.
Lanai, Matthew Bianca
Stoddard, Jennifer
Ouyane, Weiming
Frucht, David M.
Rao, V. Koneti
Atkinson, T. Prescott
Agharahimi, Anahita
Hussey, Ashleigh A.
Folioll, Les R.
Olivier, Kenneth N.
Fleisher, Thomas A.
Pittaluga, Stefania
Holland, Steven M.
Cohen, Jeffrey I.
Oliveira, Joao B.
Tangye, Stuart G.
Schwartzberg, Pamela L.
Lenardol, Michael J.
Uzel, Gulbu
TI Dominant-activating germline mutations in the gene encoding the PI(3)K
catalytic subunit p110 delta result in T cell senescence and human
immunodeficiency
SO NATURE IMMUNOLOGY
LA English
DT Article
ID IMPAIRED B-CELL; PHOSPHOINOSITIDE 3-KINASE; P85-ALPHA SUBUNIT; CLASS
IPI3K; P110 DELTA; MTOR; MEMORY; DIFFERENTIATION; KINASE; METABOLISM
AB The p110 delta subunit of phosphatidylinositol-3-OH kinase (PI(3)K) is selectively expressed in leukocytes and is critical for lymphocyte biology. Here we report fourteen patients from seven families who were heterozygous for three different germline, gain-of-function mutations in PIK3CD (which encodes p110 delta). These patients presented with sinopulmonary infections, lymphadenopathy, nodular lymphoid hyperplasia and viremia due to cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV). Strikingly, they had a substantial deficiency in naive T cells but an over-representation of senescent effector T cells. In vitro, T cells from patients exhibited increased phosphorylation of the kinase Akt and hyperactivation of the metabolic checkpoint kinase mTOR, enhanced glucose uptake and terminal effector differentiation. Notably, treatment with rapamycin to inhibit mTOR activity in vivo partially restored the abundance of naive T cells, largely 'rescued' the in vitro T cell defects and improved the clinical course.
C1 [Lucas, Carrie L.; Lanai, Matthew Bianca; Lenardol, Michael J.] NIAID, Immunol Lab, NIH, Mol Dev Immune Syst Sect, Bethesda, MD 20892 USA.
[Kuehn, Hye Sun; Niemel, Julie E.; Stoddard, Jennifer; Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD USA.
[Zhao, Fang; Cannons, Jennifer L.; Schwartzberg, Pamela L.] NHGRI, NIH, Genet Dis Res Branch, Cell Signaling Sect, Bethesda, MD 20892 USA.
[Zhao, Fang] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[Deenick, Elissa K.; Palendira, Umaimainthan; Avery, Danielle T.; Moens, Leen] Garvan Inst Med Res, Immunol & Immunodeficiency Grp, Program Immunol, Sydney, NSW, Australia.
[Deenick, Elissa K.; Palendira, Umaimainthan] Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia.
[Ouyane, Weiming; Frucht, David M.] United States Food & Drug Adm, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies,Lab Cell Biol, Bethesda, MD USA.
[Atkinson, T. Prescott] Univ Alabama Birmingham, Dept Pediat, Div Allergy & Immunol, Birmingham, AL USA.
[Olivier, Kenneth N.; Holland, Steven M.] Frederick Natl Lab Clin Res, Sci Applicatidns Int Corp Frederick, Clin Monitoring Res Program, Clin Res Directorate,Lab Clin Infect Dis, Frederick, MD USA.
[Agharahimi, Anahita] NIH, Ctr Clin, Bethesda, MD USA.
[Folioll, Les R.] Natl Canc Inst, NIH, Pathol Lab, Bethesda, MD USA.
[Pittaluga, Stefania] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Lab Infect Dis, Bethesda, MD USA.
[Cohen, Jeffrey I.] Inst Med Integral Prof Fernando Figue, Recife Pernambuco, Brazil.
RP Uzel, G (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM guzel@niaid.nih.gov
RI Tangye, Stuart/H-4023-2014;
OI Biancalana, Matthew/0000-0002-1078-1838; Oliveira,
Joao/0000-0001-9388-8173; Ouyang, Wenjun/0000-0002-1811-5864; Niemela,
Julie/0000-0003-4197-3792
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, Clinical Center of the US National Institutes of
Health; National Human Genome Research Institute of the US National
Institutes of Health; Frederick National Laboratory for Cancer Research
of the US National Institutes of Health [HHSN261200800001E]; National
Health and Medical Research Council of Australia; Cancer Council NSW;
Cancer Institute NSW; Research Foundation-Flanders, Belgium; National
Institute of General Medical Sciences
FX We thank the referring physicians, as well as the patients and families.
Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, Clinical Center of the US National
Institutes of Health (C.L.L., H.S.K., J.E.N., M.B., J.S., WO., V.K.R.,
A.A., A.A.H., K.N.O., T.A.F., S.P., S.M.H., J.I.C., M.J.L., G.U.), the
National Human Genome Research Institute of the US National Institutes
of Health (F.Z., J.L.C., P.L.S.), the Frederick National Laboratory for
Cancer Research of the US National Institutes of Health
(HHSN261200800001E), the National Health and Medical Research Council of
Australia (E.K.D., UP., S.G.T.), Cancer Council NSW (S.G.T.), the Cancer
Institute NSW (U.P.), the Research Foundation-Flanders, Belgium (L.M.)
and the National Institute of General Medical Sciences (C.L.L. and
R.Z.). The content of this publication does not necessarily reflect the
views or policies of the US Department of Health and Human Services, nor
does mention of trade names, commercial products or organizations imply
endorsement by the US Government.
NR 48
TC 131
Z9 136
U1 2
U2 28
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JAN
PY 2014
VL 15
IS 1
BP 88
EP 97
DI 10.1038/ni.2771
PG 10
WC Immunology
SC Immunology
GA 277DZ
UT WOS:000328800500016
PM 24165795
ER
PT J
AU Yu, X
Qian, CQ
Chen, DY
Dodd, SJ
Koretsky, AP
AF Yu, Xin
Qian, Chunqi
Chen, Der-yow
Dodd, Stephen J.
Koretsky, Alan P.
TI Deciphering laminar-specific neural inputs with line-scanning fMRI
SO NATURE METHODS
LA English
DT Article
ID HUMAN-BRAIN; BARREL CORTEX; SOMATOSENSORY STIMULATION; WHISKER
STIMULATION; BLOOD OXYGENATION; INITIAL DIP; MRI; RAT; CONNECTIVITY;
PLASTICITY
AB Using a line-scanning method during functional magnetic resonance imaging (fMRI), we obtained high temporal (50-ms) and spatial (50-mu m) resolution information along the cortical thickness and showed that the laminar position of fMRI onset coincides with distinct neural inputs in rat somatosensory and motor cortices. This laminar-specific fMRI onset allowed us to identify the neural inputs underlying ipsilateral fMRI activation in the barrel cortex due to peripheral denervation-induced plasticity.
C1 [Yu, Xin; Qian, Chunqi; Chen, Der-yow; Dodd, Stephen J.; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Yu, X (reprint author), NINDS, Lab Funct & Mol Imaging, US Natl Inst Hlth, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM yuxin@mail.nih.gov; koretskya@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU Intramural Research Program of the US National Institutes of
Health-NINDS
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health-NINDS. We thank K. Sharer and N. Bouraoud
for technical support.
NR 30
TC 14
Z9 14
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
EI 1548-7105
J9 NAT METHODS
JI Nat. Methods
PD JAN
PY 2014
VL 11
IS 1
BP 55
EP +
DI 10.1038/NMETH.2730
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 282NI
UT WOS:000329178200026
PM 24240320
ER
PT J
AU Renton, AE
Chio, A
Traynor, BJ
AF Renton, Alan E.
Chio, Adriano
Traynor, Bryan J.
TI State of play in amyotrophic lateral sclerosis genetics
SO NATURE NEUROSCIENCE
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; FRONTOTEMPORAL LOBAR DEGENERATION;
HEXANUCLEOTIDE REPEAT EXPANSION; SUPEROXIDE-DISMUTASE GENE; SPORADIC
ALS; SUSCEPTIBILITY LOCI; ALZHEIMERS-DISEASE; SQSTM1 MUTATIONS; SOD1
MUTATIONS; VCP MUTATIONS
AB Considerable progress has been made in unraveling the genetic etiology of amyotrophic lateral sclerosis (ALS), the most common form of adult-onset motor neuron disease and the third most common neurodegenerative disease overall. Here we review genes implicated in the pathogenesis of motor neuron degeneration and how this new information is changing the way we think about this fatal disorder. Specifically, we summarize current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C90RF72 and PFN1, and evaluate the information being gleaned from genome-wide association studies. We also outline emerging themes in ALS research, such as next-generation sequencing approaches to identify de novo mutations, the genetic convergence of familial and sporadic ALS, the proposed oligogenic basis for the disease, and how each new genetic discovery is broadening the phenotype associated with the clinical entity we know as ALS.
C1 [Renton, Alan E.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, Turin, Italy.
[Traynor, Bryan J.] Johns Hopkins Univ, Dept Neurol, Brain Sci Inst, Baltimore, MD 21218 USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
RI Traynor, Bryan/G-5690-2010;
OI Chio, Adriano/0000-0001-9579-5341
FU Intramural Research Programs of the US National Institutes of Health;
National Institute on Aging [Z01-AG000949-02]; National Institute of
Neurological Disorders and Stroke; Packard Center for ALS Research at
Hopkins; ALS Association; Microsoft Research; AriSLA; Italian Health
Ministry (Ricerca Sanitaria Finalizzata); Fondazione Vialli e Mauro
ONLUS; Federazione Italiana Giuoco Calcio; Compagnia di San Paolo;
European Community [259867]
FX This work was supported in part by the Intramural Research Programs of
the US National Institutes of Health, National Institute on Aging
(Z01-AG000949-02) and National Institute of Neurological Disorders and
Stroke. The work was also supported by the Packard Center for ALS
Research at Hopkins (B.J.T.), the ALS Association (B.J.T., A.C.),
Microsoft Research (B.J.T.), AriSLA (B.J.T., A.C.), the Italian Health
Ministry (Ricerca Sanitaria Finalizzata 2007 to A.C.), Fondazione Vialli
e Mauro ONLUS (A.C.), Federazione Italiana Giuoco Calcio (A.C., B.J.T.),
Compagnia di San Paolo (A.C.) and the European Community's Health
Seventh Framework Programme under grant agreement 259867 (A.C.).
NR 100
TC 293
Z9 301
U1 21
U2 115
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JAN
PY 2014
VL 17
IS 1
BP 17
EP 23
DI 10.1038/nn.3584
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 281DL
UT WOS:000329080000007
PM 24369373
ER
PT J
AU Bemben, MA
Shipman, SL
Hirai, T
Herring, BE
Li, Y
Badger, JD
Nicoll, RA
Diamond, JS
Roche, KW
AF Bemben, Michael A.
Shipman, Seth L.
Hirai, Takaaki
Herring, Bruce E.
Li, Yan
Badger, John D., II
Nicoll, Roger A.
Diamond, Jeffrey S.
Roche, Katherine W.
TI CaMKII phosphorylation of neuroligin-1 regulates excitatory synapses
SO NATURE NEUROSCIENCE
LA English
DT Article
ID INHIBITORY SYNAPSES; CELL-ADHESION; NMDA RECEPTORS; VISUAL-CORTEX;
NEUREXIN; BINDING; PSD-95; EXPRESSION; PLASTICITY; PROTEINS
AB Neuroligins are postsynaptic cell adhesion molecules that are important for synaptic function through their trans:synaptic interaction with neurexins (NRXNs). The localization and synaptic effects of neuroligin-1 (NL-1, also called NLGN1) are specific to excitatory synapses with the capacity to enhance excitatory synapses dependent on synaptic activity or Ca2+/calmodulin kinase II (CaMKII). Here we report that CaMKII robustly phosphorylates the intracellular domain of NL-1. We show that T739 is the dominant CaMKII site on NL-1 and is phosphorylated in response to synaptic activity in cultured rodent neurons and sensory experience in vivo. Furthermore, a phosphodeficient mutant (NL-1 T739A) reduces the basal and activity-driven surface expression of NL-1, leading to a reduction in neuroligin-mediated excitatory synaptic potentiation. To the best of our knowledge, our results are the first to demonstrate a direct functional interaction between CaMKII and NL-1, two primary components of excitatory synapses.
C1 [Bemben, Michael A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Bemben, Michael A.; Hirai, Takaaki; Badger, John D., II; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Shipman, Seth L.; Herring, Bruce E.; Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Li, Yan] NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA.
[Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
[Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
RP Roche, KW (reprint author), NINDS, Receptor Biol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
RI Diamond, Jeffrey/C-1835-2015;
OI Diamond, Jeffrey/0000-0002-1770-2629; Roche,
Katherine/0000-0001-7282-6539
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program; National Institute of Mental Health [5 R37 MH038256]
FX We are grateful to A. Sanz-Clemente and A. Scimemi for technical
assistance and for discussions on the project and manuscript. We thank
the NINDS sequencing facility and light imaging facility for their
expertise. This research was supported by the National Institute of
Neurological Disorders and Stroke Intramural Research Program (M.A.B.,
T.H., J.D.B., Y.L., J.S.D. and K.W.R.) and the National Institute of
Mental Health grant number 5 R37 MH038256 (S.L.S., B.E.H. and R.A.N.).
NR 50
TC 17
Z9 17
U1 2
U2 21
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JAN
PY 2014
VL 17
IS 1
BP 56
EP 64
DI 10.1038/nn.3601
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 281DL
UT WOS:000329080000014
PM 24336150
ER
PT J
AU Roschewski, M
Staudt, LM
Wilson, WH
AF Roschewski, Mark
Staudt, Louis M.
Wilson, Wyndham H.
TI Diffuse large B-cell lymphoma-treatment approaches in the molecular era
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID NF-KAPPA-B; PROTEASOME INHIBITOR CARFILZOMIB; RITUXIMAB PLUS
CYCLOPHOSPHAMIDE; TYROSINE KINASE INHIBITOR; NON-HODGKINS-LYMPHOMA;
CHOP-LIKE CHEMOTHERAPY; TRIAL MINT GROUP; IN-VITRO; THERAPEUTIC
STRATEGY; ANTITUMOR-ACTIVITY
AB Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell non-Hodgkin lymphoma that affects patients of all ages with a wide range of clinical presentations. Although DLBCL is curable even in advanced stages, up to one-third of patients will not achieve cure with initial therapy. In the modern era of rituximab-based therapy as the first-line treatment, the prognoses of patients who require salvage therapy are poor and most will eventually succumb to their disease. Insight into the complex molecular circuitry of DLBCL reveals a diverse range of somatic mutations and aberrant intracellular signalling pathways that characterize distinct molecular subsets of the disease. The next major breakthrough in DLBCL therapy during this 'molecular era' of disease definition will be the identification of combinations of novel agents that target the oncogenic drivers of these subsets. Well-conducted clinical trials, with translational molecular investigations, will be essential to achieve the goal of precision medicine and expand the number of patients with DLBCL who achieve a cure.
C1 [Roschewski, Mark; Staudt, Louis M.; Wilson, Wyndham H.] NCI, NIH, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA.
RP Wilson, WH (reprint author), NCI, NIH, Ctr Canc Res, Metab Branch, 9000 Rockville Pike,Bldg 10,Room 4N115, Bethesda, MD 20892 USA.
EM wilsonw@mail.nih.gov
FU NIH
FX The authors would like to acknowledge support from the intramural
research programme of the NIH.
NR 137
TC 85
Z9 88
U1 9
U2 34
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JAN
PY 2014
VL 11
IS 1
BP 12
EP 23
DI 10.1038/nrclinonc.2013.197
PG 12
WC Oncology
SC Oncology
GA 280JU
UT WOS:000329026000006
PM 24217204
ER
PT J
AU Farber, DL
Yudanin, NA
Restifo, NP
AF Farber, Donna L.
Yudanin, Naomi A.
Restifo, Nicholas P.
TI Human memory T cells: generation, compartmentalization and homeostasis
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID RESPIRATORY SYNCYTIAL VIRUS; EPSTEIN-BARR-VIRUS; HIGHLY PATHOGENIC SIV;
VERSUS-HOST-DISEASE; HUMAN BONE-MARROW; EFFECTOR-MEMORY;
INFLUENZA-VIRUS; RESIDENT MEMORY; CUTTING EDGE; VIRAL-INFECTION
AB Memory T cells constitute the most abundant lymphocyte population in the body for the majority of a person's lifetime; however, our understanding of memory T cell generation, function and maintenance mainly derives from mouse studies, which cannot recapitulate the exposure to multiple pathogens that occurs over many decades in humans. In this Review, we discuss studies focused on human memory T cells that reveal key properties of these cells, including subset heterogeneity and diverse tissue residence in multiple mucosal and lymphoid tissue sites. We also review how the function and the adaptability of human memory T cells depend on spatial and temporal compartmentalization.
C1 [Farber, Donna L.; Yudanin, Naomi A.] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA.
[Farber, Donna L.; Yudanin, Naomi A.] Columbia Univ, Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA.
[Farber, Donna L.] Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA.
[Restifo, Nicholas P.] NCI, NIH, Bethesda, MD 20892 USA.
RP Farber, DL (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, 650 West 168th St,BB1501, New York, NY 10032 USA.
EM df2396@cumc.columbia.edu
RI Yudanin, Naomi/D-1809-2014;
OI Yudanin, Naomi/0000-0002-5019-2851; Restifo, Nicholas
P./0000-0003-4229-4580
FU US National Institutes of Health [AI106697, AI100119, AI083022]
FX The authors wish to thank J. Thome and D. Turner for a critical review
of the manuscript. D.L.F. is supported by US National Institutes of
Health grants AI106697, AI100119 and AI083022.
NR 152
TC 131
Z9 136
U1 10
U2 45
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD JAN
PY 2014
VL 14
IS 1
BP 24
EP 35
DI 10.1038/nri3567
PG 12
WC Immunology
SC Immunology
GA 279LT
UT WOS:000328962200011
PM 24336101
ER
PT J
AU Miao, XY
Gu, H
Yan, LR
Lu, HZ
Wang, DJJ
Zhou, XJ
Zhuo, Y
Yang, YH
AF Miao, Xinyuan
Gu, Hong
Yan, Lirong
Lu, Hanzhang
Wang, Danny J. J.
Zhou, Xiaohong Joe
Zhuo, Yan
Yang, Yihong
TI Detecting resting-state brain activity by spontaneous cerebral blood
volume fluctuations using whole brain vascular space occupancy imaging
SO NEUROIMAGE
LA English
DT Article
DE Resting-state fMRI; Brain networks; Cerebral blood volume; VASO; BOLD
ID INDEPENDENT COMPONENT ANALYSIS; LABELING PERFUSION MEASUREMENTS;
FUNCTIONAL CONNECTIVITY; DEFAULT MODE; STRUCTURAL CONNECTIVITY; MOTOR
CORTEX; 3D GRASE; NETWORKS; MRI; FMRI
AB Resting-state brain activity has been investigated extensively using BOLD contrast. However, BOLD signal represents the combined effects of multiple physiological processes and its spatial localization is less accurate than that of cerebral blood flow and volume (CBF and CBF, respectively). In this study, we demonstrate that resting-state brain activity can be reliably detected by spontaneous fluctuations of CBV-weighted signal using whole-brain gradient and spin echo (GRASE) based vascular space occupancy (VASO) imaging. Specifically, using independent component analysis, intrinsic brain networks, including default mode, salience, executive control, visual, auditory, and sensorimotor networks were revealed robustly by the VASO technique. We further demonstrate that task-evoked VASO signal aligned well with expected gray matter areas, while blood-oxygenation level dependent (BOLD) signal extended outside of these areas probably due to their different spatial specificity. The improved spatial localization of VASO is consistent with previous studies using animal models. Moreover, we showed that the 3D-GRASE VASO images had reduced susceptibility-induced signal voiding, compared to the BOLD technique. This is attributed to the fact that VASO does not require T-2* weighting, thus the acquisition can use a shorter TE and can employ spin-echo scheme. Consequently VASO-based functional connectivity signals were well preserved in brain regions that tend to suffer from signal loss and geometric distortion in BOLD, such as orbital prefrontal cortex. Our study suggests that 3D-GRASE VASO imaging, with its improved spatial specificity and less sensitivity to susceptibility artifacts, may have advantages in resting-state fMRI studies. Published by Elsevier Inc.
C1 [Miao, Xinyuan; Zhuo, Yan] Chinese Acad Sci, Beijing MRI Ctr Brain Res, State Key Lab Brain & Cognit Sci, Inst Biophys, Beijing 100101, Peoples R China.
[Miao, Xinyuan] Univ Chinese Acad Sci, Beijing, Peoples R China.
[Miao, Xinyuan; Yan, Lirong; Wang, Danny J. J.; Zhuo, Yan] UCIA Beijing Joint Ctr Adv Brain Imaging, Beijing, Peoples R China.
[Gu, Hong; Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA.
[Yan, Lirong; Wang, Danny J. J.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
[Lu, Hanzhang] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Zhou, Xiaohong Joe] Univ Illinois, Ctr Magnet Resonance Res, Chicago, IL USA.
[Zhou, Xiaohong Joe] Univ Illinois, Ctr Magnet Resonance Res, Dept Radiol, Chicago, IL USA.
RP Zhuo, Y (reprint author), Chinese Acad Sci, Beijing MRI Ctr Brain Res, State Key Lab Brain & Cognit Sci, Inst Biophys, Beijing 100101, Peoples R China.
EM yzhuo@bcslab.ibp.ac.cn; yihongyang@intra.nida.nih.gov
FU Ministry of Science and Technology of China [2012CB825500]; National
Nature Science Foundation of China [91132302, 90820307, 30830101];
National Institute on Drug Abuse (NIDA); NIH HHS/United States [R01
NS067015/NS/NINDS]
FX We are grateful to Dr. Matthias Gunther for providing a CEASE sequence.
This work was supported in part by the Ministry of Science and
Technology of China grant (2012CB825500), the National Nature Science
Foundation of China grants (91132302, 90820307, 30830101), the
Intramural Research Program of the National Institute on Drug Abuse
(NIDA), and R01 NS067015/NS/NINDS NIH HHS/United States.
NR 50
TC 1
Z9 1
U1 1
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2014
VL 84
BP 575
EP 584
DI 10.1016/j.neuroimage.2013.09.019
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 278DF
UT WOS:000328868600053
PM 24055705
ER
PT J
AU Tsujikawa, T
Zoghbi, SS
Hong, J
Donohue, SR
Jenko, KJ
Gladding, RL
Halldin, C
Pike, VW
Innis, RB
Fujita, M
AF Tsujikawa, Tetsuya
Zoghbi, Sami S.
Hong, Jinsoo
Donohue, Sean R.
Jenko, Kimberly J.
Gladding, Robert L.
Halldin, Christer
Pike, Victor W.
Innis, Robert B.
Fujita, Masahiro
TI In vitro and in vivo evaluation of C-11-SD5024, a novel PET radioligand
for human brain imaging of cannabinoid CB1 receptors
SO NEUROIMAGE
LA English
DT Article
DE CB1 receptors; Cannabinoid; PET; Receptor imaging
ID POSITRON-EMISSION-TOMOGRAPHY; INVERSE AGONIST; SCHIZOPHRENIA; BINDING;
EXPRESSION; TRACER; MONKEY
AB We recently developed a novel cannabinoid subtype-1 (CB1) receptor radioligand C-11-SD5024 for brain imaging. This study aimed to evaluate C-11-SD5024 both in vitro and in vivo and compare it with the other CB, receptor ligands previously used in humans, i.e.,C-11-MePPEP, C-11-OMAR, F-18-MK-9470, and F-18-FMPEP-d(2). In vitro experiments were performed to measure dissociation constant (1(1) in the human brain and to measure the lipophilicity of the five CB, receptor ligands listed above. In vivo specific binding in monkeys was measured by comparing total distribution volume (V-T) at baseline and after full receptor blockade. The kinetics of C-11-SD5024 in humans were evaluated in seven healthy subjects with compartmental modeling. SD5024 showed K-i = 0.47 nM, which was at an intermediate level among the five CB, receptor ligands. Lipophilicity (LogD(7.4)) was 3.79, which is appropriate for brain imaging. Monkey scans showed high proportion of specific binding: -80% of V-T. In humans, C-11-SD5024 showed peak brain uptake of 1.5-3 standardized uptake value, which was slightly higher than that of C-11-OMAR and 18F-MK-9470. One-compartment model showed good fitting, consistent with the vast majority of brain uptake being specific binding found in the monkey. Regional V-T values were consistent with known distribution of CB1 receptors. V-T calculated from 80 and 120 mm of scan data was strongly correlated (R-2 = 0.97), indicating that 80 min provided adequate information for quantitation and that the influence of radiometabolites was low. Intersubject variability for V-T of C-11-SD5024 was 22%, which was low among the five radioligands and indicated precise measurement. In conclusion, C-11-SD5024 has appropriate affinity and lipophilicity, high specific binding, moderate brain uptake, and provides good precision to measure the binding. The results suggest that C-11-SD5024 is slightly better than or equivalent to C-11-OMAR and that both are suitable for clinical studies, especially those that involve two scans in one day. Published by Elsevier Inc.
C1 [Tsujikawa, Tetsuya; Zoghbi, Sami S.; Hong, Jinsoo; Donohue, Sean R.; Jenko, Kimberly J.; Gladding, Robert L.; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Halldin, Christer] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden.
RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM masahiro.fujita@nih.gov
FU National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH); Society of Nuclear Medicine
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH) and by the 2011/2013 Wagner-Torizuka Fellowship of
Society of Nuclear Medicine. We thank Maria Ferraris Araneta, Denise
Rallis-Frutos, Gerald Hodges, David Clark, Jeih-San Liow, and the staff
of the PET Department for assistance in successful completion of the
studies, and PMOD Technologies (Zurich, Switzerland) for providing its
image analysis and modeling software. We thank Andrew Horti (Johns
Hopkins) for providing a sample of OMAR and Terence Hamill (Merck
Research Laboratories) for providing a sample of MK-9470.
NR 28
TC 6
Z9 6
U1 0
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2014
VL 84
BP 733
EP 741
DI 10.1016/j.neuroimage.2013.09.043
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 278DF
UT WOS:000328868600067
PM 24076222
ER
PT J
AU Cao, ZJ
Zhao, YB
Tan, TT
Chen, G
Ning, XL
Zhan, LX
Yang, JJ
AF Cao, Zhijun
Zhao, Yanbing
Tan, Tengteng
Chen, Gang
Ning, Xueling
Zhan, Lexia
Yang, Jiongjiong
TI Distinct brain activity in processing negative pictures of animals and
objects - The role of human contexts
SO NEUROIMAGE
LA English
DT Article
DE Stimulus category; Emotion; Context; Amygdala; Prefrontal cortex
ID HUMAN AMYGDALA; EMOTIONAL STIMULI; SOCIAL COGNITION; FEAR; PERCEPTION;
ATTENTION; PREPAREDNESS; MECHANISMS; PHOBIAS; THREAT
AB Previous studies have shown that the amygdala is important in processing not only animate entities but also social information. It remains to be determined to what extent the factors of category and social context interact to modulate the activities of the amygdala and cortical regions. In this study, pictures depicting animals and inanimate objects in negative and neutral levels were presented. The contexts of the pictures differed in whether they included human/human parts. The factors of valence, arousal, familiarity and complexity of pictures were controlled across categories. The results showed that the amygdala activity was modulated by category and contextual information. Under the nonhuman context condition, the amygdala responded more to animals than objects for both negative and neutral pictures. In contrast, under the human context condition, the amygdala showed stronger activity for negative objects than animals. In addition to cortical regions related to object action, functional and effective connectivity analyses showed that the anterior prefrontal cortex interacted more with the amygdala for negative objects (vs. animals) in the human context condition, by a top-down modulation of the anterior prefrontal cortex to the amygdala. These results highlighted the effects of category and human contexts on modulating brain activity in emotional processing. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Cao, Zhijun; Zhao, Yanbing; Tan, Tengteng; Ning, Xueling; Zhan, Lexia; Yang, Jiongjiong] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China.
[Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, DHHS, Bethesda, MD 20892 USA.
RP Yang, JJ (reprint author), Peking Univ, Dept Psychol, Beijing 100871, Peoples R China.
EM yangjj@pku.edu.cn
FU National Science Foundation of China [31171078]; Global Research
Initiative Program, National Institutes of Health, USA [R01TW007897]
FX This research was supported by grants from the National Science
Foundation of China (31171078, J. Yang, 2012), and the Global Research
Initiative Program, National Institutes of Health, USA (R01TW007897, J.
Yang, 2008). The funders had no role in the study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 58
TC 3
Z9 3
U1 3
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2014
VL 84
BP 901
EP 910
DI 10.1016/j.neuroimage.2013.09.064
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 278DF
UT WOS:000328868600083
PM 24099847
ER
PT J
AU Horwitz, B
Simonyan, K
AF Horwitz, Barry
Simonyan, Kristina
TI PET neuroimaging: Plenty of studies still need to be performed Comment
on Cumming: "PET Neuroimaging: The White Elephant Packs His Trunk?"
SO NEUROIMAGE
LA English
DT Editorial Material
ID CEREBRAL-BLOOD-FLOW; HUMAN BRAIN; DOPAMINE RELEASE; FMRI; LANGUAGE
C1 [Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Sect Brain Imaging & Modeling, NIH, Bethesda, MD 20892 USA.
[Simonyan, Kristina] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY USA.
[Simonyan, Kristina] Icahn Sch Med Mt Sinai, Dept Otolaryngol, New York, NY USA.
RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Brain Imaging & Modeling, NIH, Bldg 10,Rm 5039,MSC 1402, Bethesda, MD 20892 USA.
EM horwitzb@mail.nih.gov
FU Intramural NIH HHS [ZIA DC000057-13, Z99 DC999999]; NIDCD NIH HHS [R00
DC009629, R00DC009629]
NR 22
TC 3
Z9 4
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JAN 1
PY 2014
VL 84
BP 1101
EP 1103
DI 10.1016/j.neuroimage.2013.09.052
PG 3
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 278DF
UT WOS:000328868600101
PM 23954490
ER
PT J
AU Jenkins, J
Calzone, KA
AF Jenkins, Jean
Calzone, Kathleen A.
TI Genomics Nursing Faculty Champion Initiative
SO NURSE EDUCATOR
LA English
DT Article
ID CARE; GENETICS
AB Nurse faculty are challenged to keep up with the emerging and fast-paced field of genomics and the mandate to prepare the nursing workforce to be able to translate genomic research advances into routine clinical care. Using Faculty Champions and other options, the initiative stimulated curriculum development and promoted genomics curriculum integration. The authors summarize this yearlong initiative for undergraduate and graduate nursing faculty.
C1 [Jenkins, Jean] NHGRI, NIH, Bethesda, MD 20892 USA.
[Calzone, Kathleen A.] NCI, NIH, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA.
RP Jenkins, J (reprint author), NHGRI, NIH, 31 Ctr Dr,Bldg 31,Rm 4B09, Bethesda, MD 20892 USA.
EM jean.jenkins@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 14
TC 4
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-3624
EI 1538-9855
J9 NURS EDUC
JI Nurs. Educ.
PD JAN-FEB
PY 2014
VL 39
IS 1
BP 8
EP 13
DI 10.1097/NNE.0000000000000011
PG 6
WC Nursing
SC Nursing
GA 279BJ
UT WOS:000328933800004
PM 24300251
ER
PT J
AU Morken, NH
Kaellen, K
Jacobsson, B
AF Morken, Nils-Halvdan
Kaellen, Karin
Jacobsson, Bo
TI Predicting Risk of Spontaneous Preterm Delivery in Women with a
Singleton Pregnancy
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE predicting risk; spontaneous preterm delivery; singleton pregnancy
ID ACUTE PYELONEPHRITIS; RENAL INFECTION; BIRTH-WEIGHT; PNEUMONIA; SYSTEM;
PREMATURITY; POPULATION; MODEL; AGE
AB BackgroundPrediction of a woman's risk of a spontaneous preterm delivery (PTD) is a core challenge and an unresolved problem in today's obstetric practice. The objective of this study was to develop prediction models for spontaneous PTD (<37 weeks).
MethodsA population-based register study of women born in Sweden with spontaneous onset of delivery was designed using Swedish Medical Birth Register data for 1992-2008. Predictive variables were identified by multiple logistic regression analysis, and outputs were used to calculate adjusted likelihood ratios in primiparous (n=199272) and multiparous (n=249580) singleton pregnant women. The predictive ability of each model was validated in a separate test sample for primiparous (n=190936) and multiparous (n=239203) women, respectively.
ResultsFor multiparous women, the area under the ROC curve (AUC) of 0.74 [95% confidence interval (CI) 0.73, 0.74] indicated a satisfying performance of the model, while for primiparous women, it was rather poor {AUC: 0.58 [95% CI 0.57, 0.58]}. For both primiparous and multiparous women, the prediction models were quite good for pregnancies with comparatively low risk for spontaneous PTD, whereas more limited to predict pregnancies with 30% risk of spontaneous PTD.
ConclusionsSpontaneous PTD is difficult to predict in multiparous women and nearly impossible in primiparous, by using this statistical method in a large and unselected sample. However, adding clinical data (like cervical length) may in the future further improve its predictive performance.
C1 [Morken, Nils-Halvdan] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway.
[Morken, Nils-Halvdan] NIEHS, Epidemiol Branch, Durham, NC USA.
[Morken, Nils-Halvdan] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
[Kaellen, Karin] Lund Univ, Tornblad Inst, Lund, Sweden.
[Jacobsson, Bo] Sahlgrens Univ Hosp, Inst Hlth Women & Children, Dept Obstet & Gynecol, S-41345 Gothenburg, Sweden.
RP Morken, NH (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Kalfarveien 31, N-5018 Bergen, Norway.
EM nils-halvdan.morken@kk.uib.no
OI Kallen, Karin/0000-0001-5765-2630
FU Goteborg Medical Society; Evy and Gunnar Sandberg foundation; Norwegian
Research Council
FX The study was supported by the Goteborg Medical Society, the Evy and
Gunnar Sandberg foundation and the Norwegian Research Council which are
acknowledged.
NR 30
TC 12
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD JAN
PY 2014
VL 28
IS 1
BP 11
EP 22
DI 10.1111/ppe.12087
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 264RX
UT WOS:000327899300003
PM 24118026
ER
PT J
AU Adgent, MA
Hoffman, K
Goldman, BD
Sjodin, A
Daniels, JL
AF Adgent, Margaret A.
Hoffman, Kate
Goldman, Barbara Davis
Sjoedin, Andreas
Daniels, Julie L.
TI Brominated Flame Retardants in Breast Milk and Behavioural and Cognitive
Development at 36 Months
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE PBDEs; halogenated diphenyl ethers; flame retardants; milk; human;
environment; environmental pollutant; epidemiology; neurobehavioural
manifestations
ID POLYBROMINATED DIPHENYL ETHERS; ACUTE POSTNATAL EXPOSURE; NEONATAL
EXPOSURE; MARKET-BASKET; ENVIRONMENT; PBDES; RATS; RECEPTORS; ATTENTION;
INFANTS
AB BackgroundPolybrominated diphenyl ethers (PBDEs) are persistent flame retardants found in the environment, in household dust, and in humans. Breast feeding is a prominent route of exposure in infancy. PBDEs adversely affect neurodevelopment in animals. Here, we estimate associations between PBDEs in breast milk and behaviour and cognitive skills in children at 36 months of age.
MethodsWe prospectively studied 304 mothers and their children. We measured PBDEs in breast milk collected at 3 months postpartum. At 36 months, we measured child behaviour with the parent-rated Behavioral Assessment System for Children 2 (n=192), and cognitive skills with the Mullen Scales of Early Learning (n=184). We analysed data with robust regression.
ResultsWe detected BDE-28, -47, -99, -100, and -153 in >70% of milk samples. For each congener, the highest quartile of breast milk PBDE concentration, vs. the lowest, was associated with more anxious behaviour, after confounder adjustment. Select congeners were associated with increased withdrawal (BDE-28) and improved activity of daily living skills (BDE-153). Cognitive skills tended to be positively associated with PBDEs, especially language and fine motor skills. However, most estimates were imprecise.
ConclusionsHere, lactational PBDE exposure was modestly and imprecisely associated with anxiety and withdrawal, but was also associated with improved adaptive and cognitive skills. Positive factors associated with breast feeding may have mitigated some of the hypothesised adverse neurodevelopmental outcomes associated with PBDEs. Further research is needed to inform our understanding of PBDE neurotoxicity and how sources of exposure might confound neurodevelopmental studies.
C1 [Adgent, Margaret A.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Hoffman, Kate; Daniels, Julie L.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Goldman, Barbara Davis] Univ N Carolina, Frank Porter Graham Child Dev Inst, Chapel Hill, NC 27599 USA.
[Goldman, Barbara Davis] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA.
[Sjoedin, Andreas] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA.
RP Daniels, JL (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA.
EM julie_daniels@unc.edu
RI Sjodin, Andreas/F-2464-2010
FU Environmental Protection Agency [RD832736]; National Institute of
Environmental Health Sciences (NIEHS) [P30ES10126]; Centers for Disease
Control and Prevention Foundation; NIEHS Environmental Biostatistics
Training Program [T32ES007018]; Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences
FX This research was supported in part by grants from the Environmental
Protection Agency (RD832736), the National Institute of Environmental
Health Sciences (NIEHS) (P30ES10126), and the Centers for Disease
Control and Prevention Foundation. The work of Kate Hoffman was
supported by the NIEHS Environmental Biostatistics Training Program
(T32ES007018). This research was supported [in part] by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences. The authors have no financial relationships relevant to this
article or conflicts of interest to disclose.
NR 41
TC 11
Z9 11
U1 4
U2 39
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD JAN
PY 2014
VL 28
IS 1
BP 48
EP 57
DI 10.1111/ppe.12078
PG 10
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 264RX
UT WOS:000327899300007
PM 24313667
ER
PT J
AU Rudnick, G
Kramer, R
Blakely, RD
Murphy, DL
Verrey, F
AF Rudnick, Gary
Kraemer, Reinhard
Blakely, Randy D.
Murphy, Dennis L.
Verrey, Francois
TI The SLC6 transporters: perspectives on structure, functions, regulation,
and models for transporter dysfunction
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Review
DE Nembrane transport; Amino acid transport; Neurotransmitter transporters;
Compatible osmolyte uptake; Neuropsychiatric disorders; Mouse models
ID TRAFFICKING-INDEPENDENT REGULATION; GLYCINE BETAINE UPTAKE; DOPAMINE D2
RECEPTOR; AMINO-ACID-TRANSPORT; SEROTONIN TRANSPORTER; NEUROTRANSMITTER
TRANSPORTERS; CORYNEBACTERIUM-GLUTAMICUM; NOREPINEPHRINE TRANSPORTER;
PROTEIN-KINASE; ALTERNATING-ACCESS
AB The human SLC6 family is composed of approximately 20 structurally related symporters (co-transporters) that use the transmembrane electrochemical gradient to actively import their substrates into cells. Approximately half of the substrates of these transporters are amino acids, with others transporting biogenic amines and/or closely related compounds, such as nutrients and compatible osmolytes. In this short review, five leaders in the field discuss a number of currently important research themes that involve SLC6 transporters, highlighting the integrative role they play across a wide spectrum of different functions. The first essay, by Gary Rudnick, describes the molecular mechanism of their coupled transport which is being progressively better understood based on new crystal structures, functional studies, and modeling. Next, the question of multiple levels of transporter regulation is discussed by Reinhard Kramer, in the context of osmoregulation and stress response by the related bacterial betaine transporter BetP. The role of selected members of the human SLC6 family that function as nutrient amino acid transporters is then reviewed by Fran double dagger ois Verrey. He discusses how some of these transporters mediate the active uptake of (essential) amino acids into epithelial cells of the gut and the kidney tubule to support systemic amino acid requirements, whereas others are expressed in specific cells to support their specialized metabolism and/or growth. The most extensively studied members of the human SLC6 family are neurotransmitter reuptake transporters, many of which are important drug targets for the treatment of neuropsychiatric disorders. Randy Blakely discusses the role of posttranscriptional modifications of these proteins in regulating transporter subcellular localization and activity state. Finally, Dennis Murphy reviews how natural gene variants and mouse genetic models display consistent behavioral alterations that relate to altered extracellular neurotransmitter levels.
C1 [Rudnick, Gary] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.
[Kraemer, Reinhard] Univ Cologne, Inst Biochem, D-50931 Cologne, Germany.
[Blakely, Randy D.] Vanderbilt Univ, Sch Med, Dept Pharmacol & Psychiat, Nashville, TN 37212 USA.
[Murphy, Dennis L.] NIMH, Clin Sci Lab, IRP, Bethesda, MD 20892 USA.
[Verrey, Francois] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland.
[Verrey, Francois] Univ Zurich, Zurich Ctr Integrat Human Physiol ZIHP, CH-8057 Zurich, Switzerland.
RP Verrey, F (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland.
EM verrey@access.uzh.ch
OI Verrey, Francois/0000-0003-3250-9824
FU Swiss NSF [31-130471/1]; National Centre of Competence in Research
(NCCR) Kidney.CH; NIH [DA007259, DA008213, MH095044, MH07802, MH073159,
MH094527]; NIMH Intramural Research Program, NIH, Bethesda, MD, USA
FX The laboratory of FV is supported by Swiss NSF grant 31-130471/1 and the
National Centre of Competence in Research (NCCR) Kidney.CH, GR by NIH
grants DA007259 and DA008213, RDB by NIH awards MH095044, MH07802,
MH073159, and MH094527. DLM is funded by the NIMH Intramural Research
Program, NIH, Bethesda, MD, USA.
NR 95
TC 26
Z9 27
U1 1
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
EI 1432-2013
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD JAN
PY 2014
VL 466
IS 1
BP 25
EP 42
DI 10.1007/s00424-013-1410-1
PG 18
WC Physiology
SC Physiology
GA 281MZ
UT WOS:000329107000003
PM 24337881
ER
PT J
AU Bachelerie, F
Ben-Baruch, A
Burkhardt, AM
Combadiere, C
Farber, JM
Graham, GJ
Horuk, R
Sparre-Ulrich, AH
Locati, M
Luster, AD
Mantovani, A
Matsushima, K
Murphy, PM
Nibbs, R
Nomiyama, H
Power, CA
Proudfoot, AEI
Rosenkilde, MM
Rot, A
Sozzani, S
Thelen, M
Yoshie, O
Zlotnik, A
AF Bachelerie, Francoise
Ben-Baruch, Adit
Burkhardt, Amanda M.
Combadiere, Christophe
Farber, Joshua M.
Graham, Gerard J.
Horuk, Richard
Sparre-Ulrich, Alexander Hovard
Locati, Massimo
Luster, Andrew D.
Mantovani, Alberto
Matsushima, Kouji
Murphy, Philip M.
Nibbs, Robert
Nomiyama, Hisayuki
Power, Christine A.
Proudfoot, Amanda E. I.
Rosenkilde, Mette M.
Rot, Antal
Sozzani, Silvano
Thelen, Marcus
Yoshie, Osamu
Zlotnik, Albert
TI International Union of Pharmacology. LXXXIX. Update on the Extended
Family of Chemokine Receptors and Introducing a New Nomenclature for
Atypical Chemokine Receptors
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID PROTEIN-COUPLED RECEPTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; REGULATORY
T-CELLS; SARCOMA-ASSOCIATED HERPESVIRUS; MACROPHAGE-DERIVED CHEMOKINE;
EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HIGH-AFFINITY BINDING;
MESSENGER-RNA EXPRESSION; DUFFY ANTIGEN RECEPTOR; CENTRAL-NERVOUS-SYSTEM
AB Sixteen years ago, the Nomenclature Committee of the International Union of Pharmacology approved a system for naming human seven-transmembrane (7TM) G protein-coupled chemokine receptors, the large family of leukocyte chemoattractant receptors that regulates immune system development and function, in large part by mediating leukocyte trafficking. This was announced in Pharmacological Reviews in a major overview of the first decade of research in this field [Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ, and Power CA (2000) Pharmacol Rev 52: 145-176]. Since then, several new receptors have been discovered, and major advances have been made for the others in many areas, including structural biology, signal transduction mechanisms, biology, and pharmacology. New and diverse roles have been identified in infection, immunity, inflammation, development, cancer, and other areas. The first two drugs acting at chemokine receptors have been approved by the U. S. Food and Drug Administration (FDA), maraviroc targeting CCR5 in human immunodeficiency virus (HIV)/AIDS, and plerixafor targeting CXCR4 for stem cell mobilization for transplantation in cancer, and other candidates are now undergoing pivotal clinical trials for diverse disease indications. In addition, a subfamily of atypical chemokine receptors has emerged that may signal through arrestins instead of G proteins to act as chemokine scavengers, and many microbial and invertebrate G protein-coupled chemokine receptors and soluble chemokine-binding proteins have been described. Here, we review this extended family of chemokine receptors and chemokine-binding proteins at the basic, translational, and clinical levels, including an update on drug development. We also introduce a new nomenclature for atypical chemokine receptors with the stem ACKR (atypical chemokine receptor) approved by the Nomenclature Committee of the International Union of Pharmacology and the Human Genome Nomenclature Committee.
C1 [Bachelerie, Francoise] Univ Paris 11, LERMIT, INSERM, UMR S996, Clamart, France.
[Ben-Baruch, Adit] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel.
[Burkhardt, Amanda M.; Zlotnik, Albert] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA.
[Combadiere, Christophe] Univ Paris 06, Lab Immunol Cellulaire, INSERM, UMR S 945, Paris, France.
[Farber, Joshua M.; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Graham, Gerard J.; Nibbs, Robert] Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow Biomed Res Ctr, Glasgow, Lanark, Scotland.
[Horuk, Richard] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA.
[Sparre-Ulrich, Alexander Hovard; Rosenkilde, Mette M.] Univ Copenhagen, Mol Pharmacol Lab, Dept Neurosci & Pharmacol, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Locati, Massimo; Mantovani, Alberto] Univ Milan, Milan, Italy.
[Locati, Massimo; Mantovani, Alberto] Humanitas Clin & Res Inst, Rozzano, Italy.
[Luster, Andrew D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA USA.
[Matsushima, Kouji] Univ Tokyo, Sch Med, Dept Mol Prevent Med, Tokyo 113, Japan.
[Nomiyama, Hisayuki] Kumamoto Univ, Dept Mol Enzymol, Grad Sch Med Sci, Kumamoto, Japan.
[Power, Christine A.] Merck Serono SA, Geneva Res Ctr, Geneva, Switzerland.
[Proudfoot, Amanda E. I.] NovImmune SA, Geneva, Switzerland.
[Rot, Antal] Univ Birmingham, Med Res Council, Ctr Immune Regulat, Inst Biomed Res,Sch Infect & Immun, Birmingham, W Midlands, England.
[Sozzani, Silvano] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy.
[Sozzani, Silvano] Humanitas Clin & Res Ctr, Rozzano, Italy.
[Thelen, Marcus] Inst Res Biomed, Bellinzona, Switzerland.
[Yoshie, Osamu] Kinki Univ, Dept Microbiol, Fac Med, Osaka, Japan.
RP Murphy, PM (reprint author), NIH, Nomenclature Comm Int Union Pharmacol, Bldg 10,Room 11N113, Bethesda, MD 20892 USA.
EM pmm@nih.gov
RI Combadiere, Christophe/I-5639-2013; Locati, Massimo/H-8404-2015;
BACHELERIE, FRANCOISE/F-8823-2013;
OI Combadiere, Christophe/0000-0002-1755-4531; Locati,
Massimo/0000-0003-3077-590X; Mantovani, Alberto/0000-0001-5578-236X;
Sozzani, Silvano/0000-0002-3144-8743
FU Intramural Research Program of the National Institutes of Health
[National Institute of Allergy and Infectious Diseases]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health [National Institute of Allergy and
Infectious Diseases].
NR 1100
TC 138
Z9 139
U1 6
U2 50
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
EI 1521-0081
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD JAN
PY 2014
VL 66
IS 1
BP 1
EP 79
DI 10.1124/pr.113.007724
PG 79
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 276NL
UT WOS:000328756900001
PM 24218476
ER
PT J
AU Richter, DW
Smith, JC
AF Richter, Diethelm W.
Smith, Jeffrey C.
TI Respiratory Rhythm Generation In Vivo
SO PHYSIOLOGY
LA English
DT Review
ID PRE-BOTZINGER COMPLEX; PERSISTENT SODIUM CURRENT; MAMMALIAN BRAIN-STEM;
RETT-SYNDROME; PACEMAKER NEURONS; GLYCINERGIC INHIBITION; PREBOTZINGER
COMPLEX; FUNCTIONAL ARCHITECTURE; GLUTAMATE RECEPTORS; INSPIRATORY
NEURONS
AB The cellular and circuit mechanisms generating the rhythm of breathing in mammals have been under intense investigation for decades. Here, we try to integrate the key discoveries into an updated description of the basic neural processes generating respiratory rhythm under in vivo conditions.
C1 [Richter, Diethelm W.] Univ Gottingen, Dept Neuro & Sensory Physiol, D-37073 Gottingen, Germany.
NINDS, Cellular & Syst Neurobiol Sect, Bethesda, MD 20892 USA.
RP Richter, DW (reprint author), Univ Gottingen, Dept Neuro & Sensory Physiol, D-37073 Gottingen, Germany.
FU DFG; DFG Research Center for Molecular Physiology of the Brain (CMPB);
National Institute of Neurological Disorders and Stroke
FX D.W. Richter was supported by DFG grants and the DFG Research Center for
Molecular Physiology of the Brain (CMPB). J. C. Smith is supported by
the Intramural Research Program of the National Institute of
Neurological Disorders and Stroke.
NR 101
TC 14
Z9 14
U1 3
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1548-9213
EI 1548-9221
J9 PHYSIOLOGY
JI Physiology
PD JAN
PY 2014
VL 29
IS 1
BP 58
EP 71
DI 10.1152/physiol.00035.2013
PG 14
WC Physiology
SC Physiology
GA 282RK
UT WOS:000329190100009
PM 24382872
ER
PT J
AU Slezak, JM
Ricaurte, GA
Tallarida, RJ
Katz, JL
AF Slezak, Jonathan M.
Ricaurte, George A.
Tallarida, Ronald J.
Katz, Jonathan L.
TI Methylphenidate and impulsivity: a comparison of effects of
methylphenidate enantiomers on delay discounting in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Methylphenidate; Psychostimulants; Delay discounting; Impulsivity;
Enantiomers; Dose equivalence; ADHD; Rat
ID DEFICIT-HYPERACTIVITY DISORDER; D-AMPHETAMINE; DECISION-MAKING;
REINFORCEMENT; PHARMACOLOGY; CHOICE; DRUGS; BEHAVIOR; MORPHINE; CHILDREN
AB Current formulations of methylphenidate (MPH) used in treatment of attention-deficit/hyperactivity disorder (ADHD) result in significantly different bioavailability of MPH enantiomers. Daytrana(A (R)), a dl-MPH transdermal patch system, produces higher levels of l-MPH than when dl-MPH is administered orally (e.g., Ritalin(A (R))). One potential limitation of increased l-MPH was indicated in a preclinical study showing l-MPH may attenuate effects of d-MPH.
The objective of the study was to investigate the interactive effects of MPH enantiomers by (1) assessing drug effects via a preclinical model of "impulsivity" and (2) performing a quantitative dose equivalence analysis of MPH enantiomer interactions.
Sprague-Dawley rats were trained to emit either of two responses, one producing an immediate food pellet, the other producing four pellets delivered at increasing delays (0, 8, and 32 s). The percent selection of the larger food amount was graphed as a function of delay with the area under the curve (AUC) assessed. Increases in AUC are consistent with decreases in "impulsivity" (i.e., selection of the smaller, immediate over the larger, delayed reinforcer).
Systemic administration of dl-MPH and d-MPH dose-dependently increased AUC, while l-MPH, morphine, and pentobarbital did not alter AUC. An analysis based upon dose equivalence indicated that dl-MPH produced additive effects that were not different from that predicted from effects of the enantiomers administered alone.
The present results indicate pharmacologically selective effects in that only drugs prescribed for the treatment of ADHD symptoms decreased a measure of "impulsivity" and that l-MPH likely does not attenuate or enhance the effects of d-MPH in the current delay-discounting task.
C1 [Slezak, Jonathan M.; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Slezak, Jonathan M.; Ricaurte, George A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Tallarida, Ronald J.] Temple Univ, Sch Med, Dept Pharmacol, Philadelphia, PA 19122 USA.
RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM jonathan.katz@intra.nida.nih.gov
OI Tallarida, Ronald/0000-0002-3760-5076; Katz,
Jonathan/0000-0002-1068-1159
FU National Institute on Drug Abuse Intramural Research Program
FX This research was supported by funds from the National Institute on Drug
Abuse Intramural Research Program.
NR 34
TC 4
Z9 4
U1 1
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JAN
PY 2014
VL 231
IS 1
BP 191
EP 198
DI 10.1007/s00213-013-3220-8
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 281NI
UT WOS:000329107900019
PM 23975034
ER
PT J
AU Dichgans, M
Malik, R
Konig, IR
Rosand, J
Clarke, R
Gretarsdottir, S
Thorleifsson, G
Mitchell, BD
Assimes, TL
Levi, C
O'Donnell, CJ
Fornage, M
Thorsteinsdottir, U
Psaty, BM
Hengstenberg, C
Seshadri, S
Erdmann, J
Bis, JC
Peters, A
Boncoraglio, GB
Marz, W
Meschia, JF
Kathiresan, S
Ikram, MA
McPherson, R
Stefansson, K
Sudlow, C
Reilly, MP
Thompson, JR
Sharma, P
Hopewell, JC
Chambers, JC
Watkins, H
Rothwell, PM
Roberts, R
Markus, HS
Samani, NJ
Farrall, M
Schunkert, H
AF Dichgans, Martin
Malik, Rainer
Koenig, Inke R.
Rosand, Jonathan
Clarke, Robert
Gretarsdottir, Solveig
Thorleifsson, Gudmar
Mitchell, Braxton D.
Assimes, Themistocles L.
Levi, Christopher
O'Donnell, Christopher J.
Fornage, Myriam
Thorsteinsdottir, Unnur
Psaty, Bruce M.
Hengstenberg, Christian
Seshadri, Sudha
Erdmann, Jeanette
Bis, Joshua C.
Peters, Annette
Boncoraglio, Giorgio B.
Maerz, Winfried
Meschia, James F.
Kathiresan, Sekar
Ikram, M. Arfan
McPherson, Ruth
Stefansson, Kari
Sudlow, Cathie
Reilly, Muredach P.
Thompson, John R.
Sharma, Pankaj
Hopewell, Jemma C.
Chambers, John C.
Watkins, Hugh
Rothwell, Peter M.
Roberts, Robert
Markus, Hugh S.
Samani, Nilesh J.
Farrall, Martin
Schunkert, Heribert
CA METASTROKE Consortium
CARDIoGRAM Consortium
C4D Consortium
Int Stroke Genetics Consortium
TI Shared Genetic Susceptibility to Ischemic Stroke and Coronary Artery
Disease A Genome-Wide Analysis of Common Variants
SO STROKE
LA English
DT Article
DE coronary artery disease; genetics; meta-analysis; polymorphism; single
nucleotide; stroke
ID ASSOCIATION METAANALYSIS; ATHEROSCLEROTIC STROKE; RISK-FACTORS; LOCI;
MORTALITY; PRESSURE; DESIGN
AB Background and Purpose Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases.
Methods Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia. We first analyzed common variants reaching a nominal threshold of significance (P<0.01) for CAD for their association with IS and vice versa. We then examined specific overlap across phenotypes for variants that reached a high threshold of significance. Finally, we conducted a joint meta-analysis on the combined phenotype of IS or CAD. Corresponding analyses were performed restricted to the 2167 individuals with the ischemic large artery stroke (LAS) subtype.
Results Common variants associated with CAD at P<0.01 were associated with a significant excess risk for IS and for LAS and vice versa. Among the 42 known genome-wide significant loci for CAD, 3 and 5 loci were significantly associated with IS and LAS, respectively. In the joint meta-analyses, 15 loci passed genome-wide significance (P<5x10(-8)) for the combined phenotype of IS or CAD and 17 loci passed genome-wide significance for LAS or CAD. Because these loci had prior evidence for genome-wide significance for CAD, we specifically analyzed the respective signals for IS and LAS and found evidence for association at chr12q24/SH2B3 (P-IS=1.62x10(-7)) and ABO (P-IS=2.6x10(-4)), as well as at HDAC9 (P-LAS=2.32x10(-12)), 9p21 (P-LAS=3.70x10(-6)), RAI1-PEMT-RASD1 (P-LAS=2.69x10(-5)), EDNRA (P-LAS=7.29x10(-4)), and CYP17A1-CNNM2-NT5C2 (P-LAS=4.9x10(-4)).
Conclusions Our results demonstrate substantial overlap in the genetic risk of IS and particularly the LAS subtype with CAD.
C1 [Dichgans, Martin; Malik, Rainer] Univ Munich, Inst Stroke & Dementia Res, Klinikum Univ Munchen, Munich, Germany.
[Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Erdmann, Jeanette] Med Univ Lubeck, Inst Integrat & Expt Genom, D-23538 Lubeck, Germany.
[Koenig, Inke R.] Univ Klinikum Schleswig Holstein, Lubeck, Germany.
[Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Rosand, Jonathan] Harvard Univ, Sch Med, Boston, MA USA.
[Rosand, Jonathan] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Kathiresan, Sekar] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, John Radcliffe Hosp, Clin Trial Serv Unit, Oxford OX3 9DU, England.
[Clarke, Robert; Hopewell, Jemma C.] Univ Oxford, John Radcliffe Hosp, Epidemiol Studies Unit, Oxford OX3 9DU, England.
[Watkins, Hugh; Farrall, Martin] Univ Oxford, John Radcliffe Hosp, Wellcome Trust Ctr Human Genet, Oxford OX3 9DU, England.
[Farrall, Martin] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England.
[Rothwell, Peter M.] Univ Oxford, John Radcliffe Hosp, Stroke Prevent Res Unit, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
[Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari] DeCODE Genet, Reykjavik, Iceland.
[Mitchell, Braxton D.] Univ Maryland Sch Med, Dept Med, Baltimore, MD USA.
[Assimes, Themistocles L.] Stanford Univ Sch Med, Dept Med, Stanford, CA USA.
[Levi, Christopher] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, Callaghan, NSW 2308, Australia.
[Levi, Christopher] Hunter Med Res Inst, New Lambton, NSW, Australia.
[O'Donnell, Christopher J.; Seshadri, Sudha] NHLBI, Bethesda, MA USA.
[O'Donnell, Christopher J.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Bethesda, MA USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
[Hengstenberg, Christian] Klin & Poliklin Innere Med II, Regensburg, Germany.
[Seshadri, Sudha] Boston Univ Sch Med, Dept Neurol, Boston, MA USA.
[Erdmann, Jeanette] DZHK German Ctr Cardiovasc Res, Lubeck, Germany.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Boncoraglio, Giorgio B.] Ist Neurol Carlo Besta, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Dept Cerebrovasc Dis, Milan, Italy.
[Maerz, Winfried] Synlab Acad, Mannheim, Germany.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA.
[Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Roberts, Robert] Univ Ottawa Heart Inst, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada.
[Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland.
[Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Thompson, John R.] Univ Leicester, Glenfield Hosp, Dept Hlth Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Leicester Natl Inst Hlth Res Biomed Res Unit Card, Leicester, Leics, England.
[Sharma, Pankaj] Imperial Coll London, ICCRU, London, England.
[Chambers, John C.] Imperial Coll London, Dept Epidemiol & Biostat, London, England.
[Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England.
[Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany.
[Schunkert, Heribert] Tech Univ Munich, German Ctr Cardiovasc Res DZHK, Munich Heart Alliance, D-80290 Munich, Germany.
RP Dichgans, M (reprint author), Klinikum Univ Munchen, ISD, Marchioninistr 15, Munich, Germany.
EM martin.dichgans@med-uni-muenchen.de; schunkert@dhm.mhn.de
RI Willenborg, Christina/D-2668-2012; Boncoraglio, Giorgio/B-8647-2011;
Kessler, Thorsten/O-7426-2015; Peters, Annette/A-6117-2011; Konig,
Inke/A-4544-2009; Erdmann, Jeanette/P-7513-2014;
OI Willenborg, Christina/0000-0001-5217-6882; Assimes,
Themistocles/0000-0003-2349-0009; Mitchell, Braxton/0000-0003-4920-4744;
Seshadri, Sudha/0000-0001-6135-2622; Ikram, Mohammad
Arfan/0000-0003-0372-8585; Erdmann, Jeanette/0000-0002-4486-6231; Bevan,
Steve/0000-0003-0490-6830; Watkins, Hugh/0000-0002-5287-9016
FU University of Newcastle; Australian National Health and Medical Research
Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G
04S 1623]; Gladys M Brawn Fellowship scheme; Vincent Fairfax Family
Foundation in Australia; National Heart, Lung, and Blood Institute
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN26820110
0008C, HHSN268201100009C, HHSN268201100010C, HHSN268 201100011C,
HHSN268201100012C, N01-HC-55015, N01-HC-55016, N01-HC-55018,
N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-85079,
N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084,
N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222,
N01-HC-75150, N01-HC-45133, N01-HC-85239, HL080295, HL087652, HL105756,
R01 HL085251, R01 HL073410, HL087647, R01HL089650-02]; National Human
Genome Research Institute [U01HG004402]; National Institutes of Health
(NIH) [HHSN268200625226C]; METASTROKE project [HL-093029]; Senior
Fellowship from the Department of Health (United Kingdom); National
Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National
Center for Research Resources [UL1RR033176, U54 RR020278]; National
Center for Advancing Translational Sciences, Clinical and Translational
Science Institute [UL1TR000124]; National Institute of Diabetes and
Digestive and Kidney Disease [DK063491]; European Community
[HEALTH-F4-2007]; FHS; National Heart, Lung, and Blood Institute's FHS
[N01-HC-25195, N02-HL-6-4278]; National Institute of Neurological
Disorders and Stroke [NS17950]; National Heart, Lung, and Blood
Association [HL93029]; National Institute of Aging [AG033193]; NIH
Genes, Environment and Health Initiative (GEI), as part of the GENEVA
consortium under the NIH Genes, Environment, and Health Initiative [U01
HG004436]; Mid-Atlantic Nutrition, and Obesity Research Center [P30
DK072488]; Office of Research and Development; Medical Research Service;
Baltimore Geriatrics Research, Education, and Clinical Center of the
Department of Veterans Affairs; NIH [HHSN268200782096C, Z01
AG-000015-50, N01-AG-12100, P01 HL098055, P01HL076491-06, R01DK080732,
P01HL087018, 1RO1HL103931-01]; Division of Adult and Community Health;
Centers for Disease Control; National Institute of Neurological
Disorders and Stroke; NIH Office of Research on Women's Health [R01
NS45012, U01 NS069208-01]; UK Medical Research Council; British Heart
Foundation (BHF); Merck & Co (manufacturers of simvastatin); Roche
Vitamins Ltd; Merck Co.; BHF Centre of Research Excellence, Oxford
[RE/08/004]; Intramural Research Program of the National Institute on
Aging, NIH project [Z01 AG-000954-06]; NIH-National Institute of
Neurological Disorders and Stroke [R01 NS-42733, R01 NS-39987, U01
NS069208]; American Heart Association/Bugher Foundation Centers for
Stroke Prevention Research [0775010 N]; National Heart, Lung, and Blood
Institute's SNP Typing for Association with Multiple Phenotypes from
Existing Epidemiologic Data (STAMPEED) genomics research program [R01
HL087676]; National Center for Research Resources; Annual Research
Funding of the Italian Ministry of Health [RC 2007/LR6, RC 2008/LR6, RC
2009/LR8, RC 2010/LR8]; Netherlands Organization of Scientific Research
[175.010.2005.011]; Netherlands Genomics Initiative (NGI)/Netherlands
Organization for Scientific Research (NWO) Netherlands Consortium for
Healthy Ageing [050-060-810]; Erasmus Medical Center and Erasmus
University, Rotterdam; Netherlands Organization for Health Research and
Development; Research Institute for Diseases in the Elderly; Ministry of
Education, Culture, and Science; Ministry for Health, Welfare, and
Sports; European Commission; Municipality of Rotterdam to the Rotterdam
Study; Netherlands Heart Foundation (Nederlandse Hartstichting)
[2009B102]; Wellcome Trust, as part of the WTCCC2 project
[085475/B/08/Z, 085475/Z/08/Z, WT084724MA]; Medical Research Council;
Stroke Association; Dunhill Medical Trust; National Institute of Health
Research (NIHR); NIHR Biomedical Research Centre, Oxford; Scottish
Funding Council; Chief Scientist Office; Vascular Dementia Research
Foundation; BHF Center of Research Excellence in Oxford; Wellcome Trust
[090532/Z/09/Z, 075491/Z/04, 084723/Z/08/Z]; Reynold's Foundation;
Boehringer Ingelheim; PHILIPS medical Systems; Government of
Rheinland-Pfalz in the context of the Stiftung Rheinland-Pfalz fur
Innovation; research program Wissenschaft Zukunft; Johannes-Gutenberg
University of Mainz in the context of the Schwerpunkt Vaskulare
Pravention; MAIFOR; Fondation de France; French Ministry of Research;
Institut National de la Sante et de la Recherche Medicale; Deutsche
Forschungsgemeinschaft; German National Genome Research Network
(NGFN-2); German National Genome Research Network (NGFN-plus); EU
[LSHM-CT-2006-037593, LSHM-CT-2004-503485, HEALTHF2-2008-201668]; US
NIH; National Heart, Lung, and Blood Institute's STAMPEED genomics
research program [R01 HL087676]; Canada Graduate Doctoral Scholarship
from the Canadian Institutes of Health Research; Cardiovascular
Institute of the University of Pennsylvania; MedStar Research Institute;
Washington Hospital Center; GlaxoSmithKline; GlaxoSmithKline through an
Alternate Drug Discovery Initiative research alliance award; University
of Pennsylvania School of Medicine; Canadian Institutes of Health
Research [MOP-82810, MOP172605, MOP77682]; Canada Foundation for
Innovation [11966]; Heart and Stroke Foundation of Ontario [NA6001];
BHF; Leicester National Institute for Health Research Biomedical
Research Unit in Cardiovascular Disease; National Institute on Aging
Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament); German Migraine &
Headache Society (DMKG); Astra Zeneca; Berlin Chemie; Boots Healthcare;
Glaxo-Smith-Kline; McNeil Pharma; MSD Sharp Dohme; Pfizer; Institute of
Epidemiology and Social Medicine, University of Muenster; Medical
Research Council (United Kingdom); Cancer Research UK; Canadian
Institutes of Health Research, Heart, and Stroke Foundation of Ontario;
Sanofi-Aventis; King Pharmaceuticals; LEEDS; Erasmus Medical Center and
Erasmus University Rotterdam; Netherlands Organization for Scientific
Research; Netherlands Organization for Health Research and Development
(ZonMw); Netherlands Heart Foundation; Ministry of Education, Culture
and Science; Ministry of Health Welfare and Sports; European Commission
(DG XII); Municipality of Rotterdam; Netherlands Organization for
Scientific Research [175.010.2005.011, 911.03.012]; NGI/NWO
[050-060-810]; Research Institute for Diseases in the Elderly (RIDE);
NWO (Vici) [918-76-619]; Swedish Research Council; Swedish Heart & Lung
Foundation; Stockholm County Council (ALF); Netherlands Heart foundation
[NHS 92345]; Netherlands Organisation for Scientific Research (NWO);
Italian Ministry of University and Research; Veneto Region; Cariverona
Foundation, Verona; Helmholtz Zentrum Munchen-National Research Center
for Environmental Health; German Federal Ministry of Education, Science,
Research and Technology; State of Bavaria; Munich Center of Health
Sciences (MC Health) as part of LMUinnovativ; Leicester NIHR Biomedical
Research Unit in Cardiovascular Disease; NIHR; European Community Sixth
Framework Program [LSHM-CT-2007-037273]; AstraZeneca; Oxford BHF Centre
of Research Excellence; Knut and Alice Wallenberg Foundation; Swedish
Heart-Lung Foundation; Torsten and Ragnar Soderberg Foundation;
Strategic Cardiovascular Program of Karolinska Institutet and Stockholm
County Council; Foundation for Strategic Research; Stockholm County
Council [560283]; National Institute for Health Research (NIHR)
Comprehensive Biomedical Research Centre Imperial College Healthcare NHS
Trust; National Institute for Health Research Cardiovascular Biomedical
Research Unit of Royal Brompton; Harefield NHS Foundation Trust; BHF
[SP/04/002]; Medical Research Council [G0601966, G0700931]; NIHR
[RP-PG-0407-10371]; European Union FP7 (EpiMigrant) [279143]; Action on
Hearing Loss [G51]; [R01HL087641]; [R01H L59367]; [R01HL086694];
[R01-HL087641]; [U01 HL096917]; [R01-HL093029]; [UL1RR025005];
[HHSN268201200036C]
FX The Australian Stroke Genetics Collaboration (ASGC): Australian
population control data were derived from the Hunter Community Study. We
also thank the University of Newcastle for funding and the men and women
of the Hunter region who participated in this study. This research was
funded by grants from the Australian National Health and Medical
Research Council (NHMRC Project Grant ID: 569257), the Australian
National Heart Foundation (NHF Project Grant ID: G 04S 1623), the
University of Newcastle, the Gladys M Brawn Fellowship scheme, and the
Vincent Fairfax Family Foundation in Australia. The Atherosclerosis Risk
in Communities Study (ARIC) is performed as a collaborative study
supported by National Heart, Lung, and Blood Institute contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN26820110
0008C, HHSN268201100009C, HHSN268201100010C, HHSN268 201100011C, and
HHSN268201100012C), R01HL087641, R01H L59367, and R01HL086694; National
Human Genome Research Institute contract U01HG004402; National
Institutes of Health (NIH) contract HHSN268200625226C; and National
Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
and grants R01-HL087641, U01 HL096917 (Mosley), and R01-HL093029
(Fornage). Infrastructure was partly supported by grant number
UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research. ARIC analyses performed as part of the METASTROKE project were
supported by grant HL-093029 to M. Fornage. Bio-Repository of DNA in
Stroke (BRAINS) is partly funded by a Senior Fellowship from the
Department of Health (United Kingdom) to Dr Sharma, the Henry Smith
Charity, and the UK-India Education Research Institutive (UKIERI) from
the British Council. Cardiovascular Health Study (CHS) research was
supported by National Heart, Lung, and Blood Institute contracts
N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083,
N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129, N01 HC-15103,
N01 HC-55222, N01-HC-75150, N01-HC-45133, N01-HC-85239, and by
HHSN268201200036C and National Heart, Lung, and Blood Institute grants
HL080295, HL087652, HL105756 with additional contribution from the
National Institute of Neurological Disorders and Stroke. Additional
support was provided through AG-023629, AG-15928, AG-20098, and
AG-027058 from the National Institute on Aging. See also
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping at
Cedars-Sinai Medical Center were supported, in part, by the National
Center for Research Resources, grant UL1RR033176, and is now at the
National Center for Advancing Translational Sciences, Clinical and
Translational Science Institute grant UL1TR000124, in addition to the
National Institute of Diabetes and Digestive and Kidney Disease grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center. deCODE Genetics Work performed at deCODE was funded, in part,
through a grant from the European Community's Seventh Framework
Programme (FP7/2007-2013), the ENGAGE project grant agreement
HEALTH-F4-2007 to 201413. The Framingham Heart Study (FHS) was supported
by the dedication of the FHS participants, the National Heart, Lung, and
Blood Institute's FHS (Contract Nos. N01-HC-25195 and N02-HL-6-4278) and
by grants from the National Institute of Neurological Disorders and
Stroke (NS17950), the National Heart, Lung, and Blood Association
(HL93029), and the National Institute of Aging (AG033193).; The Genetics
of Early Onset Stroke (GEOS) Study, Baltimore, was supported by the NIH
Genes, Environment and Health Initiative (GEI) Grant U01 HG004436, as
part of the GENEVA consortium under the NIH Genes, Environment, and
Health Initiative, with additional support provided by the Mid-Atlantic
Nutrition, and Obesity Research Center (P30 DK072488); and the Office of
Research and Development, Medical Research Service, and the Baltimore
Geriatrics Research, Education, and Clinical Center of the Department of
Veterans Affairs. Genotyping services were provided by the Johns Hopkins
University Center for Inherited Disease Research (CIDR), which is fully
funded through a federal contract from the NIH to the Johns Hopkins
University (contract number HHSN268200782096C). Assistance with data
cleaning was provided by the GENEVA Coordinating Center (U01 HG 004446;
PI Bruce S. Weir). Study recruitment and assembly of datasets were
supported by a Cooperative Agreement with the Division of Adult and
Community Health, Centers for Disease Control, and by grants from the
National Institute of Neurological Disorders and Stroke and the NIH
Office of Research on Women's Health (R01 NS45012, U01 NS069208-01).
Heart Protection Study (HPS; ISRCTN48489393) was supported by the UK
Medical Research Council, British Heart Foundation (BHF), Merck & Co
(manufacturers of simvastatin), and Roche Vitamins Ltd (manufacturers of
vitamins). Genotyping was supported by a grant to Oxford University and
Centre National de Genotypage from Merck & Co. Jemma C. Hopewell
acknowledges support from the BHF Centre of Research Excellence, Oxford
(RE/08/004). The Heart and Vascular Health Study (HVH) research reported
in this article was funded by National Heart, Lung, and Blood Institute
grants R01 HL085251 and R01 HL073410. The Ischemic Stroke Genetics Study
(ISGS)/Siblings With Ischemic Stroke Study (SWISS) was supported, in
part, by the Intramural Research Program of the National Institute on
Aging, NIH project Z01 AG-000954-06. ISGS/SWISS used samples and
clinical data from the NIH-National Institute of Neurological Disorders
and Stroke Human Genetics Resource Center DNA and Cell Line Repository
(http://ccr.coriell.org/ninds), human subjects protocol numbers 2003-081
and 2004-147. ISGS/SWISS used stroke-free participants from the
Baltimore Longitudinal Study of Aging (BLSA) as controls. The inclusion
of BLSA samples was supported, in part, by the Intramural Research
Program of the National Institute on Aging, NIH project Z01
AG-000015-50, human subjects protocol number 2003-078. The ISGS study
was funded by NIH-National Institute of Neurological Disorders and
Stroke Grant R01 NS-42733 (J.F. Meschia, P. I.). The SWISS study was
funded by NIH-National Institute of Neurological Disorders and Stroke
Grant R01 NS-39987 (J.F. Meschia, P. I.). This study used the
high-performance computational capabilities of the Biowulf Linux cluster
at the NIH (http://biowulf.nih.gov). The MGH Genes Affecting Stroke Risk
and Outcome Study (MGHGASROS) GASROS was supported by The National
Institute of Neurological Disorders and Stroke (U01 NS069208), the
American Heart Association/Bugher Foundation Centers for Stroke
Prevention Research 0775010 N, the NIH and National Heart, Lung, and
Blood Institute's SNP Typing for Association with Multiple Phenotypes
from Existing Epidemiologic Data (STAMPEED) genomics research program
(R01 HL087676), and a grant from the National Center for Research
Resources.; The Broad Institute Center for Genotyping and Analysis is
supported by grant U54 RR020278 from the National Center for Research
resources. Milano-Besta Stroke Register Collection and genotyping of the
Milan cases within Cerebrovascular Diseases Registry were supported by
Annual Research Funding of the Italian Ministry of Health (grant
numbers: RC 2007/LR6, RC 2008/LR6, RC 2009/LR8, RC 2010/LR8). FP6
LSHM-CT-2007 to 037273 for the Precocious Coronary Artery Disease
(PROCARDIS) control samples. The Rotterdam Study was supported by the
Netherlands Organization of Scientific Research (175.010.2005.011), the
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO) Netherlands Consortium for Healthy Ageing
(050-060-810), the Erasmus Medical Center and Erasmus University,
Rotterdam, The Netherlands Organization for Health Research and
Development, the Research Institute for Diseases in the Elderly, the
Ministry of Education, Culture, and Science, the Ministry for Health,
Welfare, and Sports, the European Commission, and the Municipality of
Rotterdam to the Rotterdam Study. Further funding was obtained from the
Netherlands Heart Foundation (Nederlandse Hartstichting) 2009B102. The
principal funding for the Wellcome Trust Case-Control Consortium 2
(WTCCC2) stroke study was provided by the Wellcome Trust, as part of the
WTCCC2 project (085475/B/08/Z and 085475/Z/08/Z and WT084724MA). The
Stroke Association provided additional support for collection of some of
the St George's, London cases. The Oxford cases were collected as part
of the Oxford Vascular Study, which is funded by the Medical Research
Council, Stroke Association, Dunhill Medical Trust, National Institute
of Health Research (NIHR), and the NIHR Biomedical Research Centre,
Oxford. The Edinburgh Stroke Study was supported by the Wellcome Trust
(clinician scientist award to Dr Sudlow), and the Binks Trust. Sample
processing occurred in the Genetics Core Laboratory of the Wellcome
Trust Clinical Research Facility, Western General Hospital, Edinburgh.
Much of the neuroimaging occurred in the Scottish Funding Council Brain
Imaging Research Centre (www.sbirc.ed.ac.uk), Division of Clinical
Neurosciences, University of Edinburgh, a core area of the Wellcome
Trust Clinical Research Facility and part of the Scottish Imaging
Network-A Platform for Scientific Excellence (SINAPSE) collaboration
(www.sinapse.ac.uk), funded by the Scottish Funding Council and the
Chief Scientist Office. Collection of the Munich cases and data analysis
was supported by the Vascular Dementia Research Foundation. Dr Farrall
acknowledges support from the BHF Center of Research Excellence in
Oxford and the Wellcome Trust core award (090532/Z/09/Z). The Action in
Diabetes and Vascular Disease (ADVANCE) study was supported by a grant
from the Reynold's Foundation and National Heart, Lung, and Blood
Institute grant HL087647. Genetic analyses of the Gutenberg Heart
Study/Atherogene Study (CADomics) were supported by a research grant
from Boehringer Ingelheim.; Recruitment and analysis of the CADomics
cohort were supported by grants from Boehringer Ingelheim and PHILIPS
medical Systems, by the Government of Rheinland-Pfalz in the context of
the Stiftung Rheinland-Pfalz fur Innovation, the research program
Wissenschaft Zukunft and by the Johannes-Gutenberg University of Mainz
in the context of the Schwerpunkt Vaskulare Pravention and the MAIFOR
grant 2001, by grants from the Fondation de France, the French Ministry
of Research, and the Institut National de la Sante et de la Recherche
Medicale. The deCODE CAD/MI Study was sponsored by NIH grant, National
Heart, Lung, and Blood Institute R01HL089650-02. The German MI Family
Studies (GerMIFS I-III [KORA]) were supported by the Deutsche
Forschungsgemeinschaft and the German Federal Ministry of Education and
Research (BMBF) in the context of the German National Genome Research
Network (NGFN-2 and NGFN-plus) and the EU funded integrated project
Cardiogenics (LSHM-CT-2006-037593). Ludwigshafen Risk and Cardiovascular
Health (LURIC) has received funding from the EU framework 6 funded
Integrated Project Bloodomics (LSHM-CT-2004-503485), the EU framework 7
funded Integrated Project AtheroRemo (HEALTHF2-2008-201668) and from
Sanofi/Aventis, Roche, Dade Behring/Siemens, and AstraZeneca. The
Myocardial Infarction Genetics Consortium (MIGen) study was funded by
the US NIH and National Heart, Lung, and Blood Institute's STAMPEED
genomics research program through R01 HL087676. Ron Do from the MIGen
study is supported by a Canada Graduate Doctoral Scholarship from the
Canadian Institutes of Health Research. Recruitment of PennCATH was
supported by the Cardiovascular Institute of the University of
Pennsylvania. Recruitment of the MedStar sample was supported, in part,
by the MedStar Research Institute and the Washington Hospital Center and
a research grant from GlaxoSmithKline. Genotyping of PennCATH and
Medstar was performed at the Center for Applied Genomics at the
Children's Hospital of Philadelphia and supported by GlaxoSmithKline
through an Alternate Drug Discovery Initiative research alliance award
(M. P. Reilly and D.J. Rader) with the University of Pennsylvania School
of Medicine. The Ottawa Heart Genomic Study was supported by Canadian
Institutes of Health Research #MOP-82810 (R. Roberts), Canada Foundation
for Innovation #11966 (R. Roberts), Heart and Stroke Foundation of
Ontario #NA6001 (R. McPherson), Canadian Institutes of Health Research
#MOP172605 (R. McPherson), Canadian Institutes of Health Research
#MOP77682 (A. F. R. Stewart). The WTCCC Study was funded by the Wellcome
Trust. Recruitment of cases for the WTCCC Study was performed by the BHF
Family Heart Study Research Group and supported by the BHF and the UK
Medical Research Council. N.J. Samani and S. G. Bevan hold chairs funded
by the BHF. N.J. Samani and A. H. Gschwendtner are also supported by the
Leicester National Institute for Health Research Biomedical Research
Unit in Cardiovascular Disease and the work described in this article is
part of the research portfolio of the Leicester National Institute for
Health Research Biomedical Research Unit. The Age, Gene/Environment
Susceptibility Reykjavik Study has been funded by NIH contract
N01-AG-12100, the National Institute on Aging Intramural Research
Program, Hjartavernd (the Icelandic Heart Association), and the Althingi
(the Icelandic Parliament). The Cleveland Clinic GeneBank study was
supported by NIH grants P01 HL098055, P01HL076491-06, R01DK080732,
P01HL087018, and 1RO1HL103931-01.; The collection of clinical and
sociodemographic data in the Dortmund Health Study was supported by the
German Migraine & Headache Society (DMKG) and by unrestricted grants of
equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare,
Glaxo-Smith-Kline, McNeil Pharma (former Woelm Pharma), MSD Sharp &
Dohme and Pfizer to the University of Muenster. Blood collection was
done through funds from the Institute of Epidemiology and Social
Medicine, University of Muenster. The EPIC-Norfolk study is supported by
the Medical Research Council (United Kingdom) and Cancer Research UK.
The Epidemiologic study of the determinants of diabetes, obesity and
cardiovascular disease (EpiDREAM) study is supported by the Canadian
Institutes of Health Research, Heart, and Stroke Foundation of Ontario,
Sanofi-Aventis, GlaxoSmithKline and King Pharmaceuticals. Funding for
Andrew Lotery from the LEEDS study was provided by the T. F. C. Frost
charity and the Macular Disease Society. The Rotterdam Study is
supported by the Erasmus Medical Center and Erasmus University
Rotterdam; the Netherlands Organization for Scientific Research; the
Netherlands Organization for Health Research and Development (ZonMw);
the Research Institute for Diseases in the Elderly; The Netherlands
Heart Foundation; the Ministry of Education, Culture and Science; the
Ministry of Health Welfare and Sports; the European Commission (DG XII);
and the Municipality of Rotterdam. Support for genotyping was provided
by the Netherlands Organization for Scientific Research (NWO;
175.010.2005.011, 911.03.012), the NGI/NWO project no. 050-060-810, and
Research Institute for Diseases in the Elderly (RIDE). Abbas Dehghan is
supported by a grant from NWO (Vici, 918-76-619). The SAS study was
funded by the BHF. The Swedish Research Council, the Swedish Heart &
Lung Foundation, and the Stockholm County Council (ALF) supported the
Stockholm Heart Epidemiology (SHEEP) study. Survival of Myocardial
Infarction Long-term Evaluation (SMILE) was funded by the Netherlands
Heart foundation (NHS 92345). Dr Rosendaal is a recipient of the Spinoza
Award of the Netherlands Organisation for Scientific Research (NWO),
which was used for part of this work. The Verona Heart Study was funded
by grants from the Italian Ministry of University and Research, the
Veneto Region, and the Cariverona Foundation, Verona. The KORA
(Kooperative Gesundheitsforschung in der Region Augsburg) research
platform was initiated and financed by the Helmholtz Zentrum
Munchen-National Research Center for Environmental Health, which is
funded by the German Federal Ministry of Education, Science, Research
and Technology and by the State of Bavaria. Part of this work was
financed by the German National Genome Research Network (NGFN-2 and
NGFNPlus) and within the Munich Center of Health Sciences (MC Health) as
part of LMUinnovativ. Work described in this article is part of the
research portfolio supported by the Leicester NIHR Biomedical Research
Unit in Cardiovascular Disease. This work forms part of the research
themes contributing to the translational research portfolio of Barts and
the London Cardiovascular Biomedical Research Unit, which is supported
and funded by the NIHR. The Coronary Artery Disease Genetics Consortium
(C4D) includes GWAS data contributed by the PROCARDIS, Life Sciences
Prospective Population (LOLIPOP), and HPS studies.; PROCARDIS was
supported by the European Community Sixth Framework Program
(LSHM-CT-2007-037273), AstraZeneca, the BHF, the Oxford BHF Centre of
Research Excellence, the Wellcome Trust (075491/Z/04), the Swedish
Research Council, the Knut and Alice Wallenberg Foundation, the Swedish
Heart-Lung Foundation, the Torsten and Ragnar Soderberg Foundation, the
Strategic Cardiovascular Program of Karolinska Institutet and Stockholm
County Council, the Foundation for Strategic Research, and the Stockholm
County Council (560283). The LOLIPOP study supported by the National
Institute for Health Research (NIHR) Comprehensive Biomedical Research
Centre Imperial College Healthcare NHS Trust, the National Institute for
Health Research Cardiovascular Biomedical Research Unit of Royal
Brompton and Harefield NHS Foundation Trust, the BHF (SP/04/002), the
Medical Research Council (G0601966, G0700931), the Wellcome Trust
(084723/Z/08/Z) the NIHR (RP-PG-0407-10371), European Union FP7
(EpiMigrant, 279143), and Action on Hearing Loss (G51). We thank the
participants and research staff who made the study possible.
NR 31
TC 83
Z9 84
U1 2
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JAN
PY 2014
VL 45
IS 1
BP 24
EP 36
DI 10.1161/STROKEAHA.113.002707
PG 13
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 277MJ
UT WOS:000328823400015
PM 24262325
ER
PT J
AU Ponomarev, IV
Williams, DE
Hackett, CJ
Schnell, JD
Haak, LL
AF Ponomarev, Ilya V.
Williams, Duane E.
Hackett, Charles J.
Schnell, Joshua D.
Haak, Laurel L.
TI Predicting highly cited papers: A Method for Early Detection of
Candidate Breakthroughs
SO TECHNOLOGICAL FORECASTING AND SOCIAL CHANGE
LA English
DT Article
DE Bibliometrics; Scientometrics; Highly cited papers; Breakthrough paper
indicator; Research management; Technological forecasting; Science
policy
ID RNA INTERFERENCE; CAENORHABDITIS-ELEGANS; DROSOPHILA-CELLS; SCIENCE;
INTERDISCIPLINARITY; DIFFERENTIATION; INDICATORS; CITATIONS; NETWORKS;
JOURNALS
AB Scientific breakthroughs are rare events, and usually recognized retrospectively. We developed methods for early detection of candidate breakthroughs, based on dynamics of publication citations and used a quantitative approach to identify typical citation patterns of known breakthrough papers and a larger group of highly cited papers. Based on these analyses, we proposed two forecasting models that were validated using statistical methods to derive confidence levels. These findings can be used to inform research portfolio management practices. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Ponomarev, Ilya V.; Williams, Duane E.; Schnell, Joshua D.; Haak, Laurel L.] Thomson Reuters, Custom Analyt & Engn Solut, Rockville, MD USA.
[Hackett, Charles J.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
RP Ponomarev, IV (reprint author), 1455 Res Blvd,2nd Floor, Rockville, MD 20850 USA.
EM ilya.ponomarev@thomsonreuters.com
RI Schnell, Joshua/J-4000-2012; Ponomarev, Ilya/F-5183-2010;
OI Schnell, Joshua/0000-0001-9241-7441; Ponomarev,
Ilya/0000-0002-8584-6034; Haak, Laurel/0000-0001-5109-3700; Hackett,
Charles/0000-0003-4586-9669
NR 29
TC 9
Z9 9
U1 5
U2 46
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0040-1625
EI 1873-5509
J9 TECHNOL FORECAST SOC
JI Technol. Forecast. Soc. Chang.
PD JAN
PY 2014
VL 81
BP 49
EP 55
DI 10.1016/j.techfore.2012.09.017
PG 7
WC Business; Planning & Development
SC Business & Economics; Public Administration
GA 278YP
UT WOS:000328926100005
ER
PT J
AU Rider, CV
Boekelheide, K
Catlin, N
Gordon, CJ
Morata, T
Selgrade, MK
Sexton, K
Simmons, JE
AF Rider, Cynthia V.
Boekelheide, Kim
Catlin, Natasha
Gordon, Christopher J.
Morata, Thais
Selgrade, MaryJane K.
Sexton, Kenneth
Simmons, Jane Ellen
TI Cumulative Risk: Toxicity and Interactions of Physical and Chemical
Stressors
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE cumulative risk; nonchemical stressors; joint action; radiation;
infectious disease; sunlight; temperature; noise
ID INDUCED HEARING-LOSS; GERM-CELL APOPTOSIS; CARBON-MONOXIDE;
CYTOMEGALOVIRUS-INFECTION; INCREASED SUSCEPTIBILITY; INFLAMMATORY
RESPONSES; INFLUENZA INFECTION; INDUCED HYPOTHERMIA; NOISE ANNOYANCE;
EXPOSURE
AB Recent efforts to update cumulative risk assessment procedures to incorporate nonchemical stressors ranging from physical to psychosocial reflect increased interest in consideration of the totality of variables affecting human health and the growing desire to develop community-based risk assessment methods. A key roadblock is the uncertainty as to how nonchemical stressors behave in relationship to chemical stressors. Physical stressors offer a reasonable starting place for measuring the effects of nonchemical stressors and their modulation of chemical effects (and vice versa), as they clearly differ from chemical stressors; and doses of many physical stressors are more easily quantifiable than those of psychosocial stressors. There is a commonly held belief that virtually nothing is known about the impact of nonchemical stressors on chemically mediated toxicity or the joint impact of coexposure to chemical and nonchemical stressors. Although this is generally true, there are several instances where a substantial body of evidence exists. A workshop titled Cumulative Risk: Toxicity and Interactions of Physical and Chemical Stressors held at the 2013 Society of Toxicology Annual Meeting provided a forum for discussion of research addressing the toxicity of physical stressors and what is known about their interactions with chemical stressors, both in terms of exposure and effects. Physical stressors including sunlight, heat, radiation, infectious disease, and noise were discussed in reference to identifying pathways of interaction with chemical stressors, data gaps, and suggestions for future incorporation into cumulative risk assessments.
C1 [Rider, Cynthia V.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Boekelheide, Kim; Catlin, Natasha] Brown Univ, Providence, RI 02912 USA.
[Gordon, Christopher J.] US EPA, Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Morata, Thais] NIOSH, Integrated Syst Toxicol Div, Cincinnati, OH 45226 USA.
[Selgrade, MaryJane K.] ICF Int, Durham, NC 27713 USA.
[Sexton, Kenneth] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
[Simmons, Jane Ellen] US EPA, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27709 USA.
RP Rider, CV (reprint author), NIEHS, 111 TW Alexander Dr,POB 12233,MD K2-12, Res Triangle Pk, NC 27709 USA.
EM ridercv@niehs.nih.gov
FU Superfund Research Program grant [P42ES013660]; Training grant
[T32ES07272]; National Institute of Health, National Institute of
Environmental Health Sciences
FX Superfund Research Program grant (P42ES013660 to K. B.); Training grant
(NC; T32ES07272); the Intramural Research Program of the National
Institute of Health, National Institute of Environmental Health
Sciences.
NR 54
TC 6
Z9 6
U1 3
U2 21
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JAN
PY 2014
VL 137
IS 1
BP 3
EP 11
DI 10.1093/toxsci/kft228
PG 9
WC Toxicology
SC Toxicology
GA 281XD
UT WOS:000329133400002
PM 24154487
ER
PT J
AU Peluso, MEM
Munnia, A
Bollati, V
Srivatanakul, P
Jedpiyawongse, A
Sangrajrang, S
Ceppi, M
Giese, RW
Boffetta, P
Baccarelli, AA
AF Peluso, Marco E. M.
Munnia, Armelle
Bollati, Valentina
Srivatanakul, Petcharin
Jedpiyawongse, Adisorn
Sangrajrang, Suleeporn
Ceppi, Marcello
Giese, Roger W.
Boffetta, Paolo
Baccarelli, Andrea A.
TI Aberrant Methylation of Hypermethylated-in-Cancer-1 and Exocyclic DNA
Adducts in Tobacco Smokers
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE tobacco smoking; overall and site specific methylation; HIC1; oxidative
DNA damage; M1dG
ID PHUT INDUSTRIAL ESTATE; WHITE BLOOD-CELLS; LUNG-CANCER; NEARBY
RESIDENTS; MALONDIALDEHYDE-DEOXYGUANOSINE; MOLECULAR EPIDEMIOLOGY; GENE
POLYMORPHISMS; LIPID-PEROXIDATION; RISK ALLELES; NASAL-MUCOSA
AB Tobacco smoke has been shown to produce both DNA damage and epigenetic alterations. However, the potential role of DNA damage in generating epigenetic changes is largely underinvestigated in human studies. We examined the effects of smoking on the levels of DNA methylation in genes for tumor protein p53, cyclin-dependent kinase inhibitor2A, hypermethylated-in-cancer-1 (HIC1), interleukin-6, Long Interspersed Nuclear Element type1, and Alu retrotransposons in blood of 177 residents in Thailand using bisulfite-PCR andpyrosequencing. Then, we analyzed the relationship of this methylation with the oxidative DNA adduct, M(1)dG (a malondialdehyde adduct), measured by P-32-postlabeling. Multivariate statistical analyses showed that HIC1 methylation levels were significantly increased in smokers compared with nonsmokers (p .05). A dose response was observed, with the highest HIC1 methylation levels in smokers of 10 cigarettes/day relative to nonsmokers and intermediate values in smokers of 19 cigarettes/day (p for trend .001). No additional relationships were observed. We also evaluated correlations between M(1)dG and the methylation changes at each HIC1 CpG site individually. The levels of this adduct in smokers showed a significant linear correlation with methylation at one of the 3 CpGs evaluated in HIC1: hypermethylation at position 1904864340 was significantly correlated with the adduct M(1)dG (covariate-adjusted regression coefficient () .224 .101 [SE], p .05). No other correlations were detected. Our study extends prior work by others associating hypermethylation of HIC1 with smoking; shows that a very specific hypermethylation event can arise from smoking; and encourages future studies that explore a possible role for M(1)dG in connecting smoking to this latter hypermethylation.
C1 [Peluso, Marco E. M.; Munnia, Armelle] Canc Prevent & Res Inst, Canc Risk Factor Branch, I-50139 Florence, Italy.
[Bollati, Valentina] Univ Milan, Dept Occupat & Environm Hlth, Milan, Italy.
[Bollati, Valentina] IRCCS Ca Granda Maggiore Policlin Hosp, Milan, Italy.
[Srivatanakul, Petcharin; Jedpiyawongse, Adisorn; Sangrajrang, Suleeporn] Natl Canc Inst, Div Res, Mol Epidemiol Unit, Bangkok, Thailand.
[Ceppi, Marcello] Natl Canc Inst, Mol Epidemiol Unit, Genoa, Italy.
[Giese, Roger W.] Northeastern Univ, Barnett Inst, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Lab Environm Epigenet, Boston, MA 02115 USA.
RP Peluso, MEM (reprint author), Canc Prevent & Res Inst, Canc Risk Factor Branch, Via Cosimo Vecchio 2, I-50139 Florence, Italy.
EM m.peluso@ispo.toscana.it
OI Baccarelli, Andrea/0000-0002-3436-0640; Bollati,
Valentina/0000-0002-0370-9598
FU National Cancer Institute, Bangkok, Thailand; Tuscan Tumor Institute,
Florence, Italy; "Associazione Italiana per la Ricerca sul Cancro",
Milan, Italy; U.S. National Institute of Environmental Health Sciences
[R01ES021733, R21ES021895, R21ES020010, P30ES000002, P42ES017198]
FX National Cancer Institute, Bangkok, Thailand; Tuscan Tumor Institute,
Florence, Italy; the "Associazione Italiana per la Ricerca sul Cancro",
Milan, Italy; the U.S. National Institute of Environmental Health
Sciences (R01ES021733, R21ES021895, R21ES020010, P30ES000002,
P42ES017198).
NR 55
TC 9
Z9 10
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JAN
PY 2014
VL 137
IS 1
BP 47
EP 54
DI 10.1093/toxsci/kft241
PG 8
WC Toxicology
SC Toxicology
GA 281XD
UT WOS:000329133400006
PM 24154486
ER
PT J
AU Hser, YI
Saxon, AJ
Huang, D
Hasson, A
Thomas, C
Hillhouse, M
Jacobs, P
Teruya, C
McLaughlin, P
Wiest, K
Cohen, A
Ling, W
AF Hser, Yih-Ing
Saxon, Andrew J.
Huang, David
Hasson, Al
Thomas, Christie
Hillhouse, Maureen
Jacobs, Petra
Teruya, Cheryl
McLaughlin, Paul
Wiest, Katharina
Cohen, Allan
Ling, Walter
TI Treatment retention among patients randomized to buprenorphine/naloxone
compared to methadone in a multi-site trial
SO ADDICTION
LA English
DT Article
DE Buprenorphine; methadone; opiate dependence; treatment outcomes
ID OPIOID RECEPTOR AVAILABILITY; HEROIN-DEPENDENT VOLUNTEERS; MAINTENANCE
TREATMENT; ABUSE; PHARMACOLOGY; ABSTINENCE; DIVERSION; HEALTH
AB AimsTo examine patient and medication characteristics associated with retention and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone (BUP) treatment for opioid dependence.
Design, settings and participantsThis secondary analysis included 1267 opioid-dependent individuals participating in nine opioid treatment programs between 2006 and 2009 and randomized to receive open-label BUP or MET for 24 weeks.
MeasurementsThe analyses included measures of patient characteristics at baseline (demographics; use of alcohol, cigarettes and illicit drugs; self-rated mental and physical health), medication dose and urine drug screens during treatment, and treatment completion and days in treatment during the 24-week trial.
FindingsThe treatment completion rate was 74% for MET versus 46% for BUP (P<0.01); the rate among MET participants increased to 80% when the maximum MET dose reached or exceeded 60mg/day. With BUP, the completion rate increased linearly with higher doses, reaching 60% with doses of 30-32mg/day. Of those remaining in treatment, positive opioid urine results were significantly lower [odds ratio (OR)=0.63, 95% confidence interval (CI)=0.52-0.76, P<0.01] among BUP relative to MET participants during the first 9 weeks of treatment. Higher medication dose was related to lower opiate use, more so among BUP patients. A Cox proportional hazards model revealed factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR)=1.61, CI=1.20-2.15], (ii) lower medication dose (<16mg for BUP, <60mg for MET; HR=3.09, CI=2.19-4.37), (iii) the interaction of dose and treatment condition (those with higher BUP dose were 1.04 times more likely to drop out than those with lower MET dose, and (iv) being younger, Hispanic and using heroin or other substances during treatment.
ConclusionsProvision of methadone appears to be associated with better retention in treatment for opioid dependence than buprenorphine, as does use of provision of higher doses of both medications. Provision of buprenorphine is associated with lower continued use of illicit opioids.
C1 [Hser, Yih-Ing; Huang, David; Hasson, Al; Thomas, Christie; Hillhouse, Maureen; Teruya, Cheryl; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA.
[Saxon, Andrew J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Jacobs, Petra] Natl Inst Drug Abuse, Bethesda, MD USA.
[McLaughlin, Paul] Hartford Dispensary, Hartford, CT USA.
[Cohen, Allan] Bay Area Addict Res & Treatment, Hayward, CA USA.
RP Hser, YI (reprint author), UCLA Integrated Substance Abuse Programs, 11075 Santa Monica Blvd,Suite 200, Los Angeles, CA 90025 USA.
EM yhser@ucla.edu
FU National Institute on Drug Abuse [U10 U10DA13045, K05DA017648]
FX Funding was provided by the National Institute on Drug Abuse through
grants U10 U10DA13045 and K05DA017648. The corresponding author, Yih-Ing
Hser, has full access to all the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. Author contributions to the manuscript are as follows.
Study concept and design: Y.-I.H., A.J.S., C.T., P.J. and W.L.
Acquisition of data: A.J.S., C.T., A.H., M.H., K.W., A.C. and W.L.
Analysis and interpretation of data: Y.-I.H., A.J.S., D.H., C.T.,
P.McL., A.C. and W.L. Drafting of the manuscript: Y.-I.H., A.J.S., D.H.
and W.L. Critical revision of the manuscript for important intellectual
content: Y.-I.H., A.J.S., A.H., C.T., M.H., P.J., C.T., P.McL., K.W.,
A.C. and W.L. Statistical analysis: D.H. and M.H. Obtaining funding:
Y.-I.H., A.J.S., A.H. and W.L. Administrative, technical or material
support: A.J.S., A.H., C.T., M.H. and C.T. Study supervision: Y.-I.H.,
A.J.S., C.T., P.J. and W.L.
NR 35
TC 37
Z9 38
U1 4
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD JAN
PY 2014
VL 109
IS 1
BP 79
EP 87
DI 10.1111/add.12333
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 268GD
UT WOS:000328157300012
PM 23961726
ER
PT J
AU Cippitelli, A
Damadzic, R
Hamelink, C
Brunnquell, M
Thorsell, A
Heilig, M
Eskay, RL
AF Cippitelli, Andrea
Damadzic, Ruslan
Hamelink, Carol
Brunnquell, Michael
Thorsell, Annika
Heilig, Markus
Eskay, Robert L.
TI Binge-like ethanol consumption increases corticosterone levels and
neurodegneration whereas occupancy of type II glucocorticoid receptors
with mifepristone is neuroprotective
SO ADDICTION BIOLOGY
LA English
DT Article
DE corticosterone; ethanol; FJ-B; hippocampus; mifepristone;
neurodegeneration
ID PITUITARY-ADRENAL AXIS; NEURONAL DEGENERATION; RAT HIPPOCAMPUS; SLICE
CULTURES; SPATIAL MEMORY; BRAIN-DAMAGE; ADULT RATS; EXPOSURE;
NEUROTOXICITY; STRESS
AB Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge-like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing Cort in order to achieve basal, medium, or high blood concentrations of Cort. Intragastric EtOH or an isocaloric control solution was given three times daily for 4 days to achieve blood alcohol levels ranging between 200 and 350mg/dl. Mean 24-hour plasma levels of Cort were approximate to 110 and approximate to 40ng/ml in intact EtOH-treated and intact control animals, respectively. Basal Cort replacement concentrations in EtOH-treated Adx animals did not exacerbate alcohol-induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino-cupric silver staining. In contrast, Cort replacement pellets resulting in plasma Cort levels twofold higher (medium) than normal, or greater than twofold higher (high) in Adx-Cort-EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocorticoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge-EtOH-treated intact animals, whereas, only a trend for reduction was observed in 15mg/kg/day mifepristone-treated animals in the EC, as determined by fluoro-jade B staining. These results suggest that elevated circulating Cort in part mediates EtOH-induced neurotoxicity in the brain through activation of Type II GC receptors.
C1 [Cippitelli, Andrea; Damadzic, Ruslan; Brunnquell, Michael; Thorsell, Annika; Heilig, Markus; Eskay, Robert L.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Hamelink, Carol; Eskay, Robert L.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Eskay, RL (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,1-5330, Bethesda, MD 20892 USA.
EM bobsk@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482; Thorsell, Annika/0000-0003-3535-3845
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA)-Intramural
Research Program (IRP)
FX This work was supported by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA)-Intramural Research Program (IRP). We thank Dr.
Melanie Schwandt and Karen Smith for careful revision of the paper.
NR 42
TC 13
Z9 14
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD JAN
PY 2014
VL 19
IS 1
BP 27
EP 36
DI 10.1111/j.1369-1600.2012.00451.x
PG 10
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 274MJ
UT WOS:000328610300004
PM 22500955
ER
PT J
AU Rienstra, M
Yin, XY
Larson, MG
Fontes, JD
Magnani, JW
McManus, DD
McCabe, EL
Coglianese, EE
Amponsah, M
Ho, JE
Januzzi, JL
Wollert, KC
Fradley, MG
Vasan, RS
Ellinor, PT
Wang, TJ
Benjamin, EJ
AF Rienstra, Michiel
Yin, Xiaoyan
Larson, Martin G.
Fontes, Joao D.
Magnani, Jared W.
McManus, David D.
McCabe, Elizabeth L.
Coglianese, Erin E.
Amponsah, Michael
Ho, Jennifer E.
Januzzi, James L., Jr.
Wollert, Kai C.
Fradley, Michael G.
Vasan, Ramachandran S.
Ellinor, Patrick T.
Wang, Thomas J.
Benjamin, Emelia J.
TI Relation between soluble ST2, growth differentiation factor-15, and
high-sensitivity troponin I and incident atrial fibrillation
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CHRONIC HEART-FAILURE; FAMILY-MEMBER ST2; RISK-FACTORS;
MYOCARDIAL-INFARCTION; MULTIPLE BIOMARKERS; GENERAL-POPULATION; CARDIAC
STRUCTURE; ISCHEMIC-STROKE; MORTALITY RISK; SERUM-LEVELS
AB Background We investigated whether circulating concentrations of soluble ST2, growth differentiation factor-15 (GDF-5), and high-sensitivity troponin I (hsTnI) are associated with incident atrial fibrillation (AF) and whether these biomarkers improve current risk prediction models including AF risk factors, B-type natriuretic peptide (BNP), and C-reactive protein (CRP).
Methods We studied the relation between soluble ST2, GDF-15, and hsTnI and development of AF in Framingham Heart Study participants without prevalent AF. We used Cox proportional hazard regression analysis to examine the relation of incident AF during a 10-year follow-up period with each biomarker. We adjusted for standard AF clinical risk factors, BNP, and CRP.
Results The mean age of the 3,217 participants was 59 +/- 10 years, and 54% were women. During a 10-year follow-up, 242 participants developed AF. In age-and sex-adjusted models, GDF-15 and hsTnI were associated with risk of incident AF; however, after including the AF risk factors and BNP and CRP, only hsTnI was significantly associated with AF (hazard ratio per 1 SD of loge hsTnI, 1.12, 95% CI 1.00-1.26, P = .045). The c statistic of the base model including AF risk factors, BNP, and CRP was 0.803 (95% CI 0.777-0.830) and did not improve by adding individual or all 3 biomarkers. None of the discrimination and reclassification statistics were significant compared with the base model.
Conclusion In a community-based cohort, circulating hsTnI concentrations were associated with incident AF. None of the novel biomarkers evaluated improved AF risk discrimination or reclassification beyond standard clinical AF risk factors and biomarkers.
C1 [Rienstra, Michiel; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands.
[Rienstra, Michiel; Yin, Xiaoyan; Larson, Martin G.; Fontes, Joao D.; Magnani, Jared W.; Ho, Jennifer E.; Vasan, Ramachandran S.; Wang, Thomas J.; Benjamin, Emelia J.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA.
[Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Fontes, Joao D.; Magnani, Jared W.; Ho, Jennifer E.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA.
[McCabe, Elizabeth L.; Coglianese, Erin E.; Januzzi, James L., Jr.; Fradley, Michael G.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div, Boston, MA USA.
[Coglianese, Erin E.] Loyola Univ, Div Cardiol, Chicago, IL 60611 USA.
[Amponsah, Michael] Newark Beth Israel Med Ctr, Dept Med, Newark, NJ USA.
[Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, Div Mol & Translat Cardiol, Hannover, Germany.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Wang, Thomas J.] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA.
RP Rienstra, M (reprint author), Univ Groningen, Univ Med Ctr Groningen, Thoraxctr, Dept Cardiol, POB 30-001, NL-9700 RB Groningen, Netherlands.
EM m.rienstra@umcg.nl
OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336;
Rienstra, Michiel/0000-0002-2581-070X
FU Roche Diagnostics; Critical Diagnostics; Singulex; BG Medicine; Siemens;
Thermo-Fisher
FX Dr Januzzi reports receiving grant support from Roche Diagnostics,
Critical Diagnostics, Singulex, BG Medicine, Siemens, and Thermo-Fisher.
NR 39
TC 20
Z9 20
U1 1
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD JAN
PY 2014
VL 167
IS 1
BP 109
EP +
DI 10.1016/j.ahj.2013.10.003
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 272KG
UT WOS:000328458600016
PM 24332149
ER
PT J
AU Kim, EJ
Lyass, A
Wang, N
Massaro, JM
Fox, CS
Benjamin, EJ
Magnani, JW
AF Kim, Eun-Jeong
Lyass, Asya
Wang, Na
Massaro, Joseph M.
Fox, Caroline S.
Benjamin, Emelia J.
Magnani, Jared W.
TI Relation of hypothyroidism and incident atrial fibrillation (from the
Framingham heart study)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID SUBCLINICAL THYROID-DYSFUNCTION; CARDIOVASCULAR RISK-FACTORS; C-REACTIVE
PROTEIN; OLDER PERSONS; DISEASE; MORTALITY; FAILURE; COHORT;
HYPERTHYROIDISM; MECHANISMS
AB Background Hyperthyroidism has a well-described association with atrial fibrillation (AF). However, the relation of hypothyroidism to AF has had limited investigation. Hypothyroidism is associated with cardiovascular risk factors, subclinical cardiovascular disease, and overt cardiovascular disease, all of which predispose to AF. We investigated 10-year incidence of AF in a community-dwelling cohort.
Methods Among 6,653 Framingham heart Study participants, 5,069 participants, 52% female, with mean age of 57 +/- 12 years, were eligible after excluding those with missing thyroid-stimulating hormone (TSH), TSH <0.45 mu U/L (hyperthyroid), TSH > 19.9 mu U/L, or prevalent AF. Thyroid-stimulating hormone was categorized by range (>= 0.45 to <4.5, 4.5 to <10.0, 10.0 to = 19.9 mu U/L) and by quartiles. We examined the associations between TSH and 10-year risk of AF using multivariable-adjusted Cox proportional hazards analysis.
Results Over 10-year follow-up, we observed 277 cases of incident AF. A 1-SD increase in TSH was not associated with increased risk of AF (hazard ratio 1.01, 95% CI 0.90-1.14, P = .83). In categorical analysis, using TSH >= 0.45 to <4.5 mu U/L as the referent (equivalent to euthyroid state), we found no significant association between hypothyroidism and 10-year AF risk. Comparing the highest (2.6 < TSH < 19.9 mu U/L) to lowest (0.45 < TSH < 1.3 mu U/L) quartiles of TSH further did not identify a significant association between TSH levels and 10-year risk of AF.
Conclusions In conclusion, we did not identify a significant association between hypothyroidism and 10-year risk of incident AF in a community-based study.
C1 [Kim, Eun-Jeong] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Lyass, Asya; Massaro, Joseph M.; Fox, Caroline S.; Benjamin, Emelia J.; Magnani, Jared W.] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA.
[Lyass, Asya; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Wang, Na] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Benjamin, Emelia J.; Magnani, Jared W.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA.
EM jmagnani@bu.edu
OI Benjamin, Emelia/0000-0003-4076-2336
FU American Heart Association [09FTF2190028]; NIH [6R01-NS17950,
N01-HC25195, HL092577, RO1AG028321, RC1-HL101056, 1R01HL102214]
FX This work is funded by the American Heart Association (Dr Magnani: award
no. 09FTF2190028) and the NIH (6R01-NS17950 and N01-HC25195; Dr
Benjamin: HL092577, RO1AG028321, RC1-HL101056, 1R01HL102214).
NR 28
TC 16
Z9 16
U1 1
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD JAN
PY 2014
VL 167
IS 1
BP 123
EP 126
DI 10.1016/j.ahj.2013.10.012
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 272KG
UT WOS:000328458600018
PM 24332151
ER
PT J
AU Kirkpatrick, SI
Reedy, J
Butler, EN
Dodd, KW
Subar, AF
Thompson, FE
McKinnon, RA
AF Kirkpatrick, Sharon I.
Reedy, Jill
Butler, Ebonee N.
Dodd, Kevin W.
Subar, Amy F.
Thompson, Frances E.
McKinnon, Robin A.
TI Dietary Assessment in Food Environment Research A Systematic Review
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID AGED 9-10 YEARS; VEGETABLE INTAKE; WEIGHT STATUS; OBESOGENIC
ENVIRONMENTS; INFORMATION-SYSTEMS; NEIGHBORHOOD ACCESS; CONVENIENCE
STORES; MEASUREMENT ERROR; VENDING MACHINES; SOFT DRINK
AB Context: The existing evidence on food environments and diet is inconsistent, potentially because of heterogeneity in measures used to assess diet. The objective of this review, conducted in 2012-2013, was to examine measures of dietary intake utilized in food environment research.
Evidence acquisition: Included studies were published from January 2007 through June 2012 and assessed relationships between at least one food environment exposure and at least one dietary outcome. Fifty-one articles were identified using PubMed, SCOPUS, Web of Knowledge, and PsycINFO; references listed in the papers reviewed and relevant review articles; and the National Cancer Institute's Measures of the Food Environment website. The frequency of the use of dietary intake measures and assessment of specific dietary outcomes were examined, as were patterns of results among studies using different dietary measures.
Evidence synthesis: The majority of studies used brief instruments, such as screeners or one or two questions, to assess intake. Food frequency questionnaires were used in about a quarter of studies, one in ten used 24-hour recalls, and fewer than one in 20 used diaries. Little consideration of dietary measurement error was evident. Associations between the food environment and diet were more consistently in the expected direction in studies using less error-prone measures.
Conclusions: There is a tendency toward the use of brief dietary assessment instruments with low cost and burden rather than more detailed instruments that capture intake with less bias. Use of error-prone dietary measures may lead to spurious findings and reduced power to detect associations.
C1 [Kirkpatrick, Sharon I.] Univ Waterloo, Sch Publ Hlth & Hlth Syst, Waterloo, ON N2L 3G1, Canada.
[Kirkpatrick, Sharon I.; Reedy, Jill; Butler, Ebonee N.; Subar, Amy F.; Thompson, Frances E.; McKinnon, Robin A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Dodd, Kevin W.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Butler, Ebonee N.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
RP Kirkpatrick, SI (reprint author), Univ Waterloo, Sch Publ Hlth & Hlth Syst, BMH 1036, Waterloo, ON N2L 3G1, Canada.
EM sharon.kirkpatrick@uwater-loo.ca
OI Kirkpatrick, Sharon/0000-0001-9896-5975
FU Intramural NIH HHS [Z99 CA999999]
NR 83
TC 28
Z9 28
U1 7
U2 41
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JAN
PY 2014
VL 46
IS 1
BP 94
EP 102
DI 10.1016/j.amepre.2013.08.015
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 277DO
UT WOS:000328799300014
PM 24355678
ER
PT J
AU Miettinen, M
Sarlomo-Rikala, M
McCue, P
Czapiewski, P
Langfort, R
Waloszczyk, P
Wazny, K
Biernat, W
Lasota, J
Wang, ZF
AF Miettinen, Markku
Sarlomo-Rikala, Maarit
McCue, Peter
Czapiewski, Piotr
Langfort, Renata
Waloszczyk, Piotr
Wazny, Krzysztof
Biernat, Wojciech
Lasota, Jerzy
Wang, Zengfeng
TI Mapping of Succinate Dehydrogenase Losses in 2258 Epithelial Neoplasms
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE succinate dehydrogenase subunit B; SDHB; renal cell carcinoma; prostatic
carcinoma; gastric lymphoepithelial carcinoma; seminoma
ID GASTROINTESTINAL STROMAL TUMORS; RENAL-CELL CARCINOMA; CARNEY-STRATAKIS;
GERMLINE SDHB; PARAGANGLIOMA; PHEOCHROMOCYTOMA; MUTATIONS; EXPRESSION;
GENE; HIF1-ALPHA
AB Losses in the succinate dehydrogenase (SDH) complex characterize 20% to 30% of extra-adrenal paragangliomas and 7% to 8% of gastric GISTs, and rare renal cell carcinomas. This loss is reflected as lack of the normally ubiquitous immunohistochemical expression of the SDH subunit B (SDHB). In paragangliomas, SDHB loss correlates with homozygous loss of any of the SDH subunits, typically by loss-of-function mutations. The occurrence of SDHB losses in other epithelial malignancies is unknown. In this study, we immunohistochemically examined 2258 epithelial, mostly malignant neoplasms including common carcinomas of all sites. Among renal cell carcinomas, SDHB loss was observed in 4 of 711 cases (0.6%), including a patient with an SDHB-deficient GIST. Histologically, the SDHB-negative renal carcinomas varied. There was 1 clear cell carcinoma with a high nuclear grade, 1 papillary carcinoma type 2, 1 unclassified carcinoma with a glandular pattern, and 1 oncocytoid low-grade carcinoma as previously described for SDHB-negative renal carcinoma. None of these patients was known to have paragangliomas or had loss of SDHA expression in the tumor. Three of these patients had metastases at presentation (2 in the adrenal, 1 in the retroperitoneal lymph nodes). There were no cases with SDHB loss among 64 renal oncocytomas. SDHB losses were not seen in other carcinomas, except in 1 prostatic adenocarcinoma (1/57), 1 lymphoepithelial carcinoma of the stomach, and 1 (1/40) seminoma. On the basis of this study, SDHB losses occur in 0.6% of renal cell carcinomas and extremely rarely in other carcinomas. Some of these renal carcinomas may be clinically aggressive. The clinical significance and molecular genetics of these SDHB-negative tumors requires further study.
C1 [Miettinen, Markku; Lasota, Jerzy; Wang, Zengfeng] NCI, Lab Surg Pathol, Bethesda, MD 20892 USA.
[Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, Dept Pathol, Haartman Inst, Helsinki, Finland.
[Sarlomo-Rikala, Maarit] Helsinki Univ Hosp, HusLab, Helsinki, Finland.
[McCue, Peter] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol & Cell Biol, Philadelphia, PA 19107 USA.
[McCue, Peter] Univ Hosp, Philadelphia, PA USA.
[Czapiewski, Piotr; Wazny, Krzysztof; Biernat, Wojciech] Med Univ Gdansk, Dept Pathomorphol, Gdansk, Poland.
[Langfort, Renata] Natl TB & Lung Dis Res Inst, Dept Pathol, Warsaw, Poland.
[Waloszczyk, Piotr] Zdunomed, Independent Lab Pathol, Szczecin, Poland.
RP Miettinen, M (reprint author), NCI, Lab Surg Pathol, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
RI Waloszczyk, Piotr/A-8399-2015
FU NCI's intramural research program
FX This work was supported as a part of NCI's intramural research program.
NR 28
TC 14
Z9 14
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1541-2016
EI 1533-4058
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD JAN
PY 2014
VL 22
IS 1
BP 31
EP 36
DI 10.1097/PAI.0b013e31828bfdd3
PG 6
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA 278IM
UT WOS:000328882800005
PM 23531856
ER
PT J
AU Maksymowych, WP
Learch, T
Lambert, RG
Ward, M
Haroon, N
Inman, R
Salonen, D
Gensler, LS
Weisman, MH
AF Maksymowych, Walter P.
Learch, Thomas
Lambert, Robert G.
Ward, Michael
Haroon, Nigil
Inman, Robert
Salonen, David
Gensler, Lianne S.
Weisman, Michael H.
TI Development and Validation of the Spondyloarthritis Radiography Module
for Calibration of Readers Using the Modified Stoke Ankylosing
Spondylitis Spine Score
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID RADIOLOGY INDEX; BONE-FORMATION; PROGRESSION; RELIABILITY; SENSITIVITY;
SYSTEM; COHORT; DAMAGE
AB ObjectiveTo develop and validate a reference image module aimed at calibration of readers using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) to assess radiographic progression in spondyloarthritis.
MethodsOur working group comprised 6 rheumatologists and 3 musculoskeletal radiologists. The following developmental steps were conducted: 1) review of the literature to identify aspects of the mSASSS requiring methodologic clarity; 2) independent assessment of baseline and 2-year radiographs from 25 patients using the mSASSS (pilot exercise); 3) development of a training module (the Spondyloarthritis Radiography [SPAR] module) that clarifies definitions, rules, and scoring methodology and a set of reference radiographic images; 4) scoring exercise 1 by 6 readers on 39 patients, where baseline and 2-year radiographs were scored blinded to time point; and 5) revision of the SPAR module followed by scoring exercise 2 conducted by the same 6 readers on 35 patients. Reliability of status and 2-year change scores was assessed by the intraclass correlation coefficient (ICC) method.
ResultsICCs for change scores for the radiologist reader pair improved from 0.46 to 0.62 after minimal calibration with the SPAR module. Recalibration from exercise 1 to exercise 2 with the SPAR module led to substantial improvement in interreader reliability for change in mSASSS score from ICC 0.44 (range 0.31-0.62) to ICC 0.62 (range 0.34-0.84). Simultaneous assessment of anteroposterior and lateral lumbar radiographs did not enhance reliability or detection of progression.
ConclusionCalibration according to the SPAR module led to improved reliability in the scoring of the mSASSS, even for expert readers.
C1 [Maksymowych, Walter P.; Lambert, Robert G.] Univ Alberta, Edmonton, AB T6G 2S2, Canada.
[Learch, Thomas; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Ward, Michael] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Bethesda, MD USA.
[Haroon, Nigil; Inman, Robert; Salonen, David] Univ Toronto, Toronto, ON, Canada.
[Gensler, Lianne S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Maksymowych, WP (reprint author), Univ Alberta, 562 Heritage Med Res Bldg, Edmonton, AB T6G 2S2, Canada.
EM walter.maksymowych@ualberta.ca
OI Lambert, Robert/0000-0003-0305-3290
NR 29
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
EI 2151-4658
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD JAN
PY 2014
VL 66
IS 1
BP 55
EP 62
DI 10.1002/acr.22083
PG 8
WC Rheumatology
SC Rheumatology
GA 277DF
UT WOS:000328798400010
PM 23926089
ER
PT J
AU Koonin, EV
AF Koonin, Eugene V.
TI Bacterial genes in eukaryotes: Relatively rare but real and important
SO BIOESSAYS
LA English
DT Editorial Material
ID ARCHAEA
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD JAN
PY 2014
VL 36
IS 1
BP 8
EP 8
DI 10.1002/bies.201300158
PG 1
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 271KV
UT WOS:000328391600003
PM 24323917
ER
PT J
AU Huang, XL
Zhang, F
Sun, XL
Choi, KY
Niu, G
Zhang, GF
Guo, JX
Lee, S
Chen, XY
AF Huang, Xinglu
Zhang, Fan
Sun, Xiaolian
Choi, Ki-Young
Niu, Gang
Zhang, Guofeng
Guo, Jinxia
Lee, Seulki
Chen, Xiaoyuan
TI The genotype-dependent influence of functionalized multiwalled carbon
nanotubes on fetal development
SO BIOMATERIALS
LA English
DT Article
DE Carbon nanotubes; Nanotoxicity; Genetic background; Blood-placenta
barrier; Fetal development
ID P53 TUMOR-SUPPRESSOR; BLOOD-BRAIN-BARRIER; N-ACETYLCYSTEINE; DNA-DAMAGE;
BIOMEDICAL APPLICATIONS; P53-DEFICIENT MICE; DRUG-DELIVERY; CELL FATE;
MOUSE; CANCER
AB In many cases cancer is caused by gene deficiency that is being passed along from generation to generation. Soluble carbon nanotubes (CNTs) have shown promising applications in the diagnosis and therapy of cancer, however, the potential relationship between cancer-prone individuals and response to CNT exposure as a prerequisite for development of personalized nanomedicine, is still poorly understood. Here we report that intravenous injections of multi-walled carbon nanotubes into p53 (a well-known cancer-susceptible gene) heterozygous pregnant mice can induce p53- dependent responses in fetal development. Larger sized multi-walled carbon nanotubes moved across the blood-placenta barrier (BPB), restricted the development of fetuses, and induced brain deformity, whereas single-walled and smaller sized multi-walled carbon nanotubes showed no or less fetotoxicity. A molecular mechanism study found that multi-walled carbon nanotubes directly triggered p53-dependent apoptosis and cell cycle arrest in response to DNA damage. Based on the molecular mechanism, we also incorporated N-acetylcysteine (NAC), an FDA approved antioxidant, to prevent CNTs induced nuclear DNA damage and reduce brain development abnormalities. Our findings suggest that CNTs might have genetic background-dependent toxic effect on the normal development of the embryo, and provide new insights into protection against nanoparticle-induced toxicity in potential clinical applications. Published by Elsevier Ltd.
C1 [Huang, Xinglu; Zhang, Fan; Sun, Xiaolian; Choi, Ki-Young; Niu, Gang; Guo, Jinxia; Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
[Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed LOMIN, NIH, 31 Ctr Dr,31-1C22, Bethesda, MD 20892 USA.
EM Shawn.Chen@nih.gov
RI CHOI, KI YOUNG/Q-7177-2016
FU Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health. We thank Dr. Henry S. Eden for proofreading the manuscript
and Ms. Myungsun Lee for drawing the scheme.
NR 62
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U1 7
U2 40
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD JAN
PY 2014
VL 35
IS 2
BP 856
EP 865
DI 10.1016/j.biomaterials.2013.10.027
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 274GM
UT WOS:000328594800024
PM 24344357
ER
PT J
AU Schindler, CW
Thorndike, EB
Blough, BE
Tella, SR
Goldberg, SR
Baumann, MH
AF Schindler, Charles W.
Thorndike, Eric B.
Blough, Bruce E.
Tella, Srihari R.
Goldberg, Steven R.
Baumann, Michael H.
TI Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main
metabolites on cardiovascular function in conscious rats
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE MDMA metabolites; heart rate; BP; noradrenergic; telemetry
ID 3,4-DIHYDROXYMETHAMPHETAMINE HHMA; HEALTHY-VOLUNTEERS;
LOCOMOTOR-ACTIVITY; ARRIVE GUIDELINES; SQUIRREL-MONKEYS; ECSTASY;
HUMANS; RESPONSES; COCAINE; PHARMACOKINETICS
AB Background and Purpose The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy') contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats.
Experimental Approach Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats.
Key Results MDMA (1-20mgkg(-1)) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10mgkg(-1)) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the -adrenoceptor antagonist propranolol.
Conclusions and Implications Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMAin vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study.
C1 [Schindler, Charles W.; Thorndike, Eric B.; Goldberg, Steven R.] NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Blough, Bruce E.] RTI Int, Res Triangle Pk, NC USA.
[Tella, Srihari R.] Drug Enforcement Adm, Off Divers Control, Drug & Chem Evaluat Sect, Springfield, VA USA.
[Baumann, Michael H.] NIDA, Med Chem Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Schindler, CW (reprint author), NIDA, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM cschind@helix.nih.gov
FU National Institutes of Health, National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Drug Abuse. The
views expressed are those of the authors and do not necessarily
represent the views of the Drug Enforcement Administration, the US
Department of Justice or an officer or entity of the USA.
NR 48
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U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD JAN
PY 2014
VL 171
IS 1
BP 83
EP 91
DI 10.1111/bph.12423
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 266HJ
UT WOS:000328014400007
PM 24328722
ER
PT J
AU Weisberg, J
Milleville, SC
Kenworthy, L
Wallace, GL
Gotts, SJ
Beauchamp, MS
Martin, A
AF Weisberg, Jill
Milleville, Shawn C.
Kenworthy, Lauren
Wallace, Gregory L.
Gotts, Stephen J.
Beauchamp, Michael S.
Martin, Alex
TI Social Perception in Autism Spectrum Disorders: Impaired Category
Selectivity for Dynamic but not Static Images in Ventral Temporal Cortex
SO CEREBRAL CORTEX
LA English
DT Article
DE Asperger's syndrome; autism; fusiform gyrus; MRI/fMRI; social cognition
ID POSTERIOR PARIETAL CORTEX; EPISODIC MEMORY RETRIEVAL; VISUAL-SPATIAL
ATTENTION; LATERAL OCCIPITAL CORTEX; BOTTOM-UP ATTENTION; EVENT-RELATED
FMRI; RECOGNITION MEMORY; RETINOTOPIC ORGANIZATION; INTRAPARIETAL
SULCUS; WORKING-MEMORY
AB Studies of autism spectrum disorders (ASDs) reveal dysfunction in the neural systems mediating object processing (particularly faces) and social cognition, but few investigations have systematically assessed the specificity of the dysfunction. We compared cortical responses in typically developing adolescents and those with ASD to stimuli from distinct conceptual domains known to elicit category-related activity in separate neural systems. In Experiment 1, subjects made category decisions to photographs, videos, and point-light displays of people and tools. In Experiment 2, subjects interpreted displays of simple, geometric shapes in motion depicting social or mechanical interactions. In both experiments, we found a selective deficit in the ASD subjects for dynamic social stimuli (videos and point-light displays of people, moving geometric shapes), but not static images, in the functionally localized lateral region of the right fusiform gyrus, including the fusiform face area. In contrast, no group differences were found in response to either static images or dynamic stimuli in other brain regions associated with face and social processing (e. g. posterior superior temporal sulcus, amygdala), suggesting disordered connectivity between these regions and the fusiform gyrus in ASD. This possibility was confirmed by functional connectivity analysis.
C1 [Weisberg, Jill; Milleville, Shawn C.; Kenworthy, Lauren; Wallace, Gregory L.; Gotts, Stephen J.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20850 USA.
[Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA.
[Beauchamp, Michael S.] Univ Texas Med Sch Houston, Dept Neurobiol & Anat, Houston, TX 77030 USA.
RP Weisberg, J (reprint author), San Diego State Univ Res Fdn, Lab Language & Cognit Neurosci, 6495 Alvarado Rd,Suite 200, San Diego, CA 92120 USA.
EM jweisberg@projects.sdsu.edu
OI Beauchamp, Michael/0000-0002-7599-9934; Wallace,
Gregory/0000-0003-0329-5054
FU National Institute of Mental Health [5R01-MH080309]; NSF [BCS 0920865]
FX This work was supported by a grant from the National Institute of Mental
Health (5R01-MH080309) and support for KSW from the NSF (BCS 0920865).
NR 101
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Z9 13
U1 3
U2 27
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JAN
PY 2014
VL 24
IS 1
BP 37
EP 66
DI 10.1093/cercor/bhs276
PG 30
WC Neurosciences
SC Neurosciences & Neurology
GA 271EE
UT WOS:000328373300003
PM 23019245
ER
PT J
AU Bertelsen, RJ
Faeste, CK
Granum, B
Egaas, E
London, SJ
Carlsen, KH
Carlsen, KCL
Lovik, M
AF Bertelsen, R. J.
Faeste, C. K.
Granum, B.
Egaas, E.
London, S. J.
Carlsen, K. -H.
Carlsen, K. C. Lodrup
Lovik, M.
TI Food allergens in mattress dust in Norwegian homes - a potentially
important source of allergen exposure
SO CLINICAL AND EXPERIMENTAL ALLERGY
LA English
DT Article
DE adolescents; dust samples; food allergens; home characteristics; indoor
environment
ID HOUSEHOLD PEANUT CONSUMPTION; VACUUM CLEANERS; CHILDREN; ASTHMA;
SENSITIZATION; STABILITY; AVOIDANCE; CONTACT; PROTEIN; NORWAY
AB BackgroundSensitization to food allergens and food allergic reactions are mostly caused by ingesting the allergen, but can also occur from exposure via the respiratory tract or the skin. Little is known about exposure to food allergens in the home environment.
ObjectiveThe objective of this study was firstly to describe the frequency of detection of allergens from fish, egg, milk, and peanut in mattress dust collected from homes of 13-year-old adolescents and secondly to identify home characteristics associated with the presence of food allergen contamination in dust.
MethodsFood allergens were measured by dot blot analysis in mattress dust from 143 homes in Oslo, Norway. We analysed associations between home characteristics (collected by parental questionnaires and study technicians) and food allergens by multivariate regression models.
ResultsFish allergen was detected in 46%, peanut in 41%, milk in 39%, and egg allergen in 22% of the mattress dust samples; only three samples contained none of these allergens. All four food allergens were more frequently detected in mattresses in small dwellings (<100m(2)) than larger dwellings (130m(2)); 63-71% of the small dwellings (n=24) had milk, peanut, and fish allergens in the samples compared with 33-44% of the larger dwellings (n=95). Milk, peanut, and egg allergens were more frequently detected in homes with bedroom and kitchen on the same floor as compared with different floors, with odds ratios of 2.5 (95% confidence interval (CI): 1.1, 5.6) for milk, 2.4 (95% CI: 1.0, 6.1) for peanut, and 3.1 (95% CI: 1.3, 7.5) for egg allergens.
Conclusions and clinical relevanceFood allergens occurred frequently in beds in Norwegian homes, with dwelling size and proximity of kitchen and bedroom as the most important determinants. Due to the amount of time children spent in the bedroom, mattress dust may be an important source of exposure to food allergens.
C1 [Bertelsen, R. J.; Granum, B.; Lovik, M.] Norwegian Inst Publ Hlth, Dept Food Water & Cosmet, N-0403 Oslo, Norway.
[Bertelsen, R. J.; London, S. J.] NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
[Faeste, C. K.; Egaas, E.] Norwegian Vet Inst, Dept Chem & Toxicol, Oslo, Norway.
[Carlsen, K. -H.; Carlsen, K. C. Lodrup] Oslo Univ Hosp, Dept Pediat, Oslo, Norway.
[Carlsen, K. -H.; Carlsen, K. C. Lodrup] Univ Oslo, Fac Med, Oslo, Norway.
RP Bertelsen, RJ (reprint author), Norwegian Inst Publ Hlth, Dept Food Water & Cosmet, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM randi.jacobsen.bertelsen@helse-bergen.no
OI Granum, Berit/0000-0002-3401-8132; London, Stephanie/0000-0003-4911-5290
FU Norwegian Institute of Public Health, Research Council of Norway, Oslo
University Hospital; Norwegian Veterinary Institute; Intramural Research
Program of the National Institute of Environmental Health Sciences
(NIEHS); National Institutes of Health (NIH)
FX We are very thankful to Jan Sundell who kindly shared the protocol used
for home inspection in the "Dampness in Buildings and Health' study
performed in Sweden in 2001-2002. We also would like to thank Sveinung
Berntsen, Geir Hetland, Ellen Namork, Solvor Berntsen Stolevik, Kristian
Helland-Hansen, Elisabeth Hovas Fulsebakke, Lars Quiller, Ole Gunnar
Ovstaas, Oddbjorn Sjovold, and students from Oslo University College,
Faculty of Engineering. This study was funded by the Norwegian Institute
of Public Health, Research Council of Norway, Oslo University Hospital,
and the Norwegian Veterinary Institute. The study was performed within
ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood), a
member of GA2LEN (Global Allergy and Asthma European Network). This
research was supported in part by the Intramural Research Program of the
National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH). The authors have no financial relationships
relevant to this article to disclose.
NR 34
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U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-7894
EI 1365-2222
J9 CLIN EXP ALLERGY
JI Clin. Exp. Allergy
PD JAN
PY 2014
VL 44
IS 1
BP 142
EP 149
DI 10.1111/cea.12231
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 275AR
UT WOS:000328647900017
PM 24304208
ER
PT J
AU Li, RC
Krishnamoorthy, P
DerOhannessian, S
Doveikis, J
Wilcox, M
Thomas, P
Rader, DJ
Reilly, MP
Van Voorhees, A
Gelfand, JM
Mehta, NN
AF Li, R. C.
Krishnamoorthy, P.
DerOhannessian, S.
Doveikis, J.
Wilcox, M.
Thomas, P.
Rader, D. J.
Reilly, M. P.
Van Voorhees, A.
Gelfand, J. M.
Mehta, N. N.
TI Psoriasis is associated with decreased plasma adiponectin levels
independently of cardiometabolic risk factors
SO CLINICAL AND EXPERIMENTAL DERMATOLOGY
LA English
DT Article
ID ADIPOSE-TISSUE; INSULIN-RESISTANCE; METABOLIC SYNDROME; INFLAMMATION;
ADIPOKINES; EXPRESSION; IMMUNITY; OBESITY
AB BackgroundPsoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known.
MethodsA consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis, were recruited for this case-control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status.
ResultsParticipants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13g/mL [interquartile range (IQR) 4.9-11.3) vs. 14.5g/mL (IQR 8.4-24.1); P<0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4-21.8) vs. 9.8 (IQR 4.9-20.5); P=0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference=-41.2%, P<0.001), insulin resistance (% difference=-39.5%, P<0.001), and both waist size and insulin resistance (% difference=-38.5%, P<0.001).
ConclusionsPlasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct studies of adipose tissue are needed to confirm this.
C1 [Li, R. C.; Krishnamoorthy, P.; DerOhannessian, S.; Doveikis, J.; Wilcox, M.; Rader, D. J.; Reilly, M. P.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Li, R. C.; Rader, D. J.; Reilly, M. P.; Gelfand, J. M.] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Thomas, P.] Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Van Voorhees, A.; Gelfand, J. M.] Hosp Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA.
[Mehta, N. N.] NHLBI, Bethesda, MD 20892 USA.
RP Mehta, NN (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
FU R01 grant [HL111293]; National Heart, Lung, Blood Institute of the
National Institutes of Health [NHLBI Z99 HL999999]; National Psoriasis
Foundation Discovery Grant; Doris Duke Charitable Foundation
FX This work was supported in part by R01 grant HL111293 (to JMG) and by an
intramural grant from the National Heart, Lung, Blood Institute of the
National Institutes of Health, grant number NHLBI Z99 HL999999 (NNM).
NNM was a recipient of a National Psoriasis Foundation Discovery Grant.
This work was also supported by a grant from the Doris Duke Charitable
Foundation (to RCL). The funding sources had no role in the design or
conduct of the study; collection, management, analysis, or
interpretation of the data; or preparation, review, or approval of the
manuscript.
NR 22
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U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0307-6938
EI 1365-2230
J9 CLIN EXP DERMATOL
JI Clin. Exp. Dermatol.
PD JAN
PY 2014
VL 39
IS 1
BP 19
EP 24
DI 10.1111/ced.12250
PG 6
WC Dermatology
SC Dermatology
GA 273ZC
UT WOS:000328573800004
PM 24341476
ER
PT J
AU Tompkins, DA
Smith, MT
Bigelow, GE
Moaddel, R
Venkata, SLV
Strain, EC
AF Tompkins, David Andrew
Smith, Michael T.
Bigelow, George E.
Moaddel, Ruin
Venkata, Swarajya Lakshmi Vatem
Strain, Eric C.
TI The Effect of Repeated Intramuscular Alfentanil Injections on
Experimental Pain and Abuse Liability Indices in Healthy Males
SO CLINICAL JOURNAL OF PAIN
LA English
DT Article
DE cold pressor; alfentanil; abuse liability; opioid-induced hyperalgesia;
algometer
ID COLD PRESSOR TEST; OPIOID-INDUCED HYPERALGESIA; OPIATE ADDICTS; IM
ALFENTANIL; VOLUNTEERS; MORPHINE; HUMANS; MODEL; REMIFENTANIL;
PSYCHOMOTOR
AB Objective:Opioid-induced hyperalgesia (OIH), increased sensitivity to noxious stimuli after repeated opioid exposures, has been demonstrated in preclinical studies. However, there is no accepted, prospective model of OIH after repeated opioid exposures currently available in humans. This study assessed a potential prospective OIH model.
Methods:Double-blind intramuscular injections of a short-acting opioid (alfentanil 15 mcg/kg; N=8) were compared to active placebo (diphenhydramine 25 mg; N=3) on cold and pressure pain testing and standard abuse liability measures in eight 10-hour sessions (1 injection/session) over 4 to 5 weeks in healthy, pain-free males. Decreases from session baseline pain threshold (PThr) and tolerance (PTol) were calculated to represent hyperalgesia, and were assessed both within and across sessions.
Results:Mean decreases in cold PTol were seen in the alfentanil group at 180 minutes (-3.8 s, 26.5) and 480 minutes (-1.63 s, +/- 31.5) after drug administration. There was a trend for differences between conditions on cold PThr hyperalgesia but not for pressure PThr. Alfentanil participants had greater mean ratings on Liking and High visual analog scales at peak effects (30 min), but these scores did not change across sessions.
Discussion:Repeated alfentanil exposures over 4 to 5 weeks resulted in within session decreases in cold pain tolerance from baseline but these differences were not substantially different from diphenhydramine controls. The results did not support the phenomenon of OIH in this model, although definitive conclusions regarding the existence of OIH in humans likely requires a larger sample size or an alternative model.
C1 [Tompkins, David Andrew; Bigelow, George E.; Strain, Eric C.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Pharmacol Res Unit, Baltimore, MD 21205 USA.
[Smith, Michael T.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Behav Sleep Med Program, Baltimore, MD 21205 USA.
[Moaddel, Ruin; Venkata, Swarajya Lakshmi Vatem] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Tompkins, DA (reprint author), Johns Hopkins Bayview Med Campus,5510 Nathan Shoc, Baltimore, MD 21231 USA.
EM dtompki1@jhmi.edu
OI Tompkins, David/0000-0002-2112-2299
FU NIDA [5T32 DA07209, 1K24DA023186]; Intramural Research Program of the
NIH, National Institute on Aging, Baltimore, MD
FX Supported by grants from NIDA: 5T32 DA07209 and 1K24DA023186. Supported
in part by the Intramural Research Program of the NIH, National
Institute on Aging, Baltimore, MD.
NR 56
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U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0749-8047
EI 1536-5409
J9 CLIN J PAIN
JI Clin. J. Pain
PD JAN
PY 2014
VL 30
IS 1
BP 36
EP 45
DI 10.1097/AJP.0b013e3182851758
PG 10
WC Anesthesiology; Clinical Neurology
SC Anesthesiology; Neurosciences & Neurology
GA 274TV
UT WOS:000328630000005
PM 23446076
ER
PT J
AU Mohan, KVK
Rao, SS
Gao, Y
Atreya, CD
AF Mohan, K. V. K.
Rao, S. Sainath
Gao, Y.
Atreya, C. D.
TI Enhanced antimicrobial activity of peptide-cocktails against common
bacterial contaminants of ex vivo stored platelets
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Article
DE Antimicrobial peptides; bactericidal; colony-forming units; pathogen
reduction; platelet-derived peptides
ID IN-VITRO ACTIVITIES; MICROBICIDAL PROTEINS; STAPHYLOCOCCUS-AUREUS;
EXPERIMENTAL ENDOCARDITIS; INNATE IMMUNITY; ARGININE-RICH;
SUSCEPTIBILITY; COMBINATION; MECHANISMS; RESISTANCE
AB Bacterial contamination of blood components such as ex vivo-stored platelets is a major safety risk in transfusion medicine. We have recently shown that synthetic antimicrobial peptides named PD1-PD4 derived from the thrombin-induced human platelet-derived antimicrobial proteins, and repeats of Arg-Trp (RW1-RW5) demonstrate microbicidal activity against selected bacteria and viruses. In the present study, we selected PD3, PD4, RW2, RW3 and RW4 and evaluated each individual peptide and their various combinations to see whether the cocktail regimen enhances the antimicrobial activity above and over the individual peptides. Stored platelet or plasma samples spiked with known titres of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Bacillus cereus were treated with either individual peptides or with peptides in various combinations. Analyses revealed that individual peptides show moderate microbicidal activity (10- to 100-fold reduction) against the tested bacteria relative to their combined regimen. The peptide combinations (RW2+RW4, RW2+RW3+RW4 and PD4+RW3+RW4) on the other hand enhanced the microbicidal activity (c.10000-fold reduction) and revealed a minimal inhibitory concentration of 5M. Time-kill kinetics indicated that these three peptide combinations exhibited enhanced antimicrobial activity bringing about a 100-fold reduction of bacterial titres within 20min of incubation. The present study therefore demonstrates the synergistic effect of antimicrobial peptides when used in combinations and provides a proof-of-concept of its potential application as a molecular tool towards pathogen reduction and further extends the possibility of using peptide combinatorial therapeutics as broad-spectrum antibiotics or as alternatives to combat drug-resistant bacteria.
C1 [Mohan, K. V. K.; Rao, S. Sainath; Atreya, C. D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Bethesda, MD 20014 USA.
[Gao, Y.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Mohan, KVK (reprint author), Bldg 29A,Room 2C-15,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA.
EM krishna.ketha@fda.hhs.gov
FU Center for Biologics Evaluation and Research (CBER); US Department of
Energy; US Food and Drug Administration
FX SSR is a recipient of a postdoctoral fellowship at the Center for
Biologics Evaluation and Research (CBER) administered by the Oak Ridge
Institute for Science and Education through an intra-agency agreement
between the US Department of Energy and the US Food and Drug
Administration. Review of the manuscript by Drs Salim Haddad and
Vladimir Lugovstev, of CBER, is highly appreciated.
NR 30
TC 1
Z9 1
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1198-743X
EI 1469-0691
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD JAN
PY 2014
VL 20
IS 1
BP O39
EP O46
DI 10.1111/1469-0691.12326
PG 8
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 273JK
UT WOS:000328530900017
PM 23926880
ER
PT J
AU Meert, KL
Eggly, S
Berg, RA
Wessel, DL
Newth, CJL
Shanley, TP
Harrison, R
Dalton, H
Clark, AE
Dean, JM
Doctor, A
Nicholson, CE
AF Meert, Kathleen L.
Eggly, Susan
Berg, Robert A.
Wessel, David L.
Newth, Christopher J. L.
Shanley, Thomas P.
Harrison, Rick
Dalton, Heidi
Clark, Amy E.
Dean, J. Michael
Doctor, Allan
Nicholson, Carol E.
CA Eunice Kennedy Shriver Natl Inst C
Collaborative Pediat Critical Care
TI Feasibility and Perceived Benefits of a Framework for Physician-Parent
Follow-Up Meetings After a Child's Death in the PICU
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE bereavement; death; follow-up; intensive care; parents; pediatrics;
physicians
ID INTENSIVE-CARE-UNIT; OF-LIFE CARE; PALLIATIVE CARE; BEREAVEMENT;
PERSPECTIVES; FAMILY; RECOMMENDATIONS; COMMUNICATION; GUIDELINES;
MEDICINE
AB Objective: To evaluate the feasibility and perceived benefits of conducting physician-parent follow-up meetings after a child's death in the PICU according to a framework developed by the Collaborative Pediatric Critical Care Research Network.
Design: Prospective observational study.
Setting: Seven Collaborative Pediatric Critical Care Research Network-affiliated children's hospitals.
Subjects: Critical care attending physicians, bereaved parents, and meeting guests (i.e., parent support persons, other health professionals).
Interventions: Physician-parent follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework.
Measurements and Main Results: Forty-six critical care physicians were trained to conduct follow-up meetings using the framework. All meetings were video recorded. Videos were evaluated for the presence or absence of physician behaviors consistent with the framework. Present behaviors were evaluated for performance quality using a 5-point scale (1 = low, 5 = high). Participants completed meeting evaluation surveys. Parents of 194 deceased children were mailed an invitation to a follow-up meeting. Of these, one or both parents from 39 families (20%) agreed to participate, 80 (41%) refused, and 75 (39%) could not be contacted. Of 39 who initially agreed, three meetings were canceled due to conflicting schedules. Thirty-six meetings were conducted including 54 bereaved parents, 17 parent support persons, 23 critical care physicians, and 47 other health professionals. Physician adherence to the framework was high; 79% of behaviors consistent with the framework were rated as present with a quality score of 4.30.2. Of 50 evaluation surveys completed by parents, 46 (92%) agreed or strongly agreed the meeting was helpful to them and 40 (89%) to others they brought with them. Of 36 evaluation surveys completed by critical care physicians (i.e., one per meeting), 33 (92%) agreed or strongly agreed the meeting was beneficial to parents and 31 (89%) to them.
Conclusions: Follow-up meetings using the Collaborative Pediatric Critical Care Research Network framework are feasible and viewed as beneficial by meeting participants. Future research should evaluate the effects of follow-up meetings on bereaved parents' health outcomes.
C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Eggly, Susan] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
[Berg, Robert A.] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA.
[Wessel, David L.] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care, Los Angeles, CA 90027 USA.
[Shanley, Thomas P.] Univ Michigan, CS Mott Childrens Hosp, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Harrison, Rick] Univ Calif Los Angeles, Mattel Childrens Hosp, Dept Child Hlth, Los Angeles, CA USA.
[Dalton, Heidi] Phoenix Childrens Hosp, Dept Pediat, Phoenix, AZ USA.
[Clark, Amy E.; Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Doctor, Allan] St Louis Childrens Hosp, Dept Pediat, St Louis, MO 63110 USA.
[Doctor, Allan] St Louis Childrens Hosp, Dept Biochem, St Louis, MO 63178 USA.
[Nicholson, Carol E.] NICHHD, Bethesda, MD 20892 USA.
RP Meert, KL (reprint author), Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
EM kmeert@med.wayne.edu
OI Doctor, Allan/0000-0002-6096-6400; Eggly, Susan/0000-0002-8137-6098
FU National Institute of Child Health and Human Development [U10HD050096,
U10HD049981, U10HD063108, U10HD063106, U10HD063114, U10HD050012,
U01HD049934]; Department of Health and Human Services; National
Institutes of Health (NIH); NICHD grant; NICHD; NIH
FX Supported, in part, by grants U10HD050096, U10HD049981, U10HD063108,
U10HD063106, U10HD063114, U10HD050012, and U01HD049934 in cooperative
agreements from the National Institute of Child Health and Human
Development and the Department of Health and Human Services.; Dr. Meert
has received grant support and travel reimbursements from the National
Institutes of Health (NIH). Dr. Berg's institution has received a NICHD
grant as a site PI for the Collaborative Pediatric Critical Care
Research Network. Drs. Eggly, Wessel, Dalton, Clark, and Dean receive
support from the National Institutes of Health (NIH). Dr. Newth is
supported by a grant from NICHD, U10 (Collaborative Pediatric Critical
Care Research Network). Dr. Shanley received grant support from the NIH;
is a board member for EAB Univ Cinci; and provides expert testimony to
Lawson-Wilson; receives payment for lectures from Advances in
Neonatology; and receives royalties from Springer. Dr. Harrison has
received grant support from the NIH and payment for lectures and
travel/accommodations from SCCM. Drs. Doctor and Nicholson disclosed
that they do not have any potential conflicts of interest.
NR 30
TC 7
Z9 7
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JAN
PY 2014
VL 42
IS 1
BP 148
EP 157
DI 10.1097/CCM.0b013e3182a26ff3
PG 10
WC Critical Care Medicine
SC General & Internal Medicine
GA 274OK
UT WOS:000328615600037
PM 24105453
ER
PT J
AU Matteini, AM
Li, J
Lange, EM
Tanaka, T
Lange, LA
Tracy, RP
Wang, Y
Biggs, ML
Arking, DE
Fallin, MD
Chakravarti, A
Psaty, BM
Bandinelli, S
Ferrucci, L
Reiner, AP
Walston, JD
AF Matteini, A. M.
Li, J.
Lange, E. M.
Tanaka, T.
Lange, L. A.
Tracy, R. P.
Wang, Y.
Biggs, M. L.
Arking, D. E.
Fallin, M. D.
Chakravarti, A.
Psaty, B. M.
Bandinelli, S.
Ferrucci, L.
Reiner, A. P.
Walston, J. D.
TI Novel gene variants predict serum levels of the cytokines IL-18 and
IL-1ra in older adults
SO CYTOKINE
LA English
DT Article
DE Chronic inflammation; Genome-wide association studies; Older adults
ID GENOME-WIDE ASSOCIATION; C-REACTIVE PROTEIN; CLUSTER POLYMORPHISMS;
INTERLEUKIN-1 FAMILY; FIBRINOGEN LEVELS; CARCINOMA-CELLS; ANTAGONIST
GENE; RISK; INFLAMMATION; HAPLOTYPES
AB Activation of inflammatory pathways measured by serum inflammatory markers such as interleukin-18 (IL-18) and interleukin-1 receptor antagonist (IL-1ra) is strongly associated with the progression of chronic disease states in older adults. Given that these serum cytokine levels are in part a heritable trait, genetic variation may predict increased serum levels. Using the Cardiovascular Health Study and InCHIANTI cohorts, a genome-wide association study was performed to identify genetic variants that influence IL-18 and IL-1ra serum levels among older adults. Multiple linear regression models characterized the association between each SNP and log-transformed cytokine values. Tests for multiple independent signals within statistically significant loci were performed using haplotype analysis and regression models conditional on lead SNP in each region. Multiple SNPs were associated with these cytokines with genome-wide significance, including SNPs in the IL-18-BCO gene region of chromosome 2 for IL-18 (top SNP rs2250417, P=1.9 x 10(-32)) and in the IL-1 gene family region of chromosome 2 for IL-1ra (rs6743376, P=2.3 x 10(-26)). Haplotype tests and conditional linear regression models showed evidence of multiple independent signals in these regions. Serum IL-18 levels were also associated with a region on chromosome 2 containing the NLRC4 gene (rs12989936, P = 2.7 x 10(-19)). These data characterize multiple robust genetic signals that influence IL-18 and IL-1ra cytokine production. In particular, the signal for serum IL-18 located on chromosome two is novel and potentially important in inflammasome triggered chronic activation of inflammation in older adults. Replication in independent cohorts is an important next step, as well as molecular studies to better understand the role of NLRC4. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Matteini, A. M.; Walston, J. D.] Johns Hopkins Med Inst, Div Geriatr Med, Baltimore, MD 21205 USA.
[Li, J.; Lange, E. M.; Lange, L. A.; Wang, Y.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Tanaka, T.; Ferrucci, L.] NIA, Translat Gerontol Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Tracy, R. P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Tracy, R. P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
[Biggs, M. L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Arking, D. E.; Chakravarti, A.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Fallin, M. D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, B. M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Bandinelli, S.] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Reiner, A. P.] Univ Washington, Dept Med, Seattle, WA USA.
[Reiner, A. P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Reiner, A. P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Matteini, AM (reprint author), 2024 East Monument St,Suite 2-726, Baltimore, MD 21205 USA.
EM amatteini@jhmi.edu
FU Johns Hopkins Older Americans Independence Center [P30 AG021334];
National Heart, Lung, and Blood Institute (NHLBI) [HL080295]; National
Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058];
Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging [263 MD 9164, 263 MD 821336]; [R01 AG027236]; [R01 HL071862];
[HHSN268201200036C]; [N01-HC-85239]; [N01-HC-85079]; [N01-HC-85080];
[N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083]; [N01-HC-85084];
[N01-HC-85085]; [N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103];
[N01-HC-55222]; [N01-HC-75150]; [N01-HC-45133]; [HL087652]
FX This study was supported by Grants R01 AG027236 (Dr. Walston), R01
HL071862 (Dr. Reiner) and by the Johns Hopkins Older Americans
Independence Center, P30 AG021334. The Cardiovascular Health Study was
supported by contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079
through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01-HC-55222,
N01-HC-75150, N01-HC-45133, and Grant HL080295 from the National Heart,
Lung, and Blood Institute (NHLBI), with additional contribution from the
National Institute of Neurological Disorders and Stroke (NINDS).
Additional support was provided through AG-023629, AG-15928, AG-20098,
and AG-027058 from the National Institute on Aging (NIA). CHS genotyping
was supported by HL087652. A full list of participating CHS
investigators and institutions can be found at
http://www.chs-nhIbi.org/pi.htm. 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 MD 9164 and 263 MD 821336).
NR 45
TC 11
Z9 11
U1 1
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD JAN
PY 2014
VL 65
IS 1
BP 10
EP 16
DI 10.1016/j.cyto.2013.10.002
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 275YU
UT WOS:000328716100003
PM 24182552
ER
PT J
AU Zhou, Q
Hu, Y
Howard, OMZ
Oppenheim, JJ
Chen, X
AF Zhou, Qiong
Hu, Ya
Howard, O. M. Zack
Oppenheim, Joost J.
Chen, Xin
TI In vitro generated Th17 cells support the expansion and phenotypic
stability of CD4(+)Foxp3(+) regulatory T cells in vivo
SO CYTOKINE
LA English
DT Article
DE Th17; Regulatory T cell; IL-2; TNF; TNFR2
ID INFLAMMATORY-DISEASES; HELPER 17; DIFFERENTIATION; T(H)17; EXPRESSION;
PROMOTES; LINEAGE; IL-2; RECEPTORS; DISTINCT
AB CD4(+) T cells stimulate immune responses through distinct patterns of cytokine produced by Th1, Th2 or Th17 cells, or inhibit immune responses through Foxp3-expressing regulatory T cells (Tregs). Paradoxically, effector T cells were recently shown to activate Tregs, however, it remains unclear which Th subset is responsible for this effect. In this study, we found that Th17 cells expressed the highest levels of TNF among in vitro generated Th subsets, and most potently promoted expansion and stabilized Foxp3 expression by Tregs when co-transferred into Rag1(-/-) mice. Both TNF and IL-2 produced by Th17 cells contributed to this effect. The stimulatory effect of Th17 cells on Tregs was largely abolished when co-transferred with TNFR2-deficient Tregs. Furthermore, Tregs deficient in TNFR2 also supported a much lower production of IL-17A and TNF expression by co-transferred Th17 cells. Thus, our data indicate that the TNF-TNFR2 pathway plays a crucial role in the reciprocal stimulatory effect of Th17 cells and Tregs. This bidirectional interaction should be taken into account when designing therapy targeting Th17 cells, Tregs, TNF and TNFR2. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Zhou, Qiong; Hu, Ya; Howard, O. M. Zack; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Chen, Xin] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Chen, X (reprint author), NCI, LMI, Bldg 560,Rm 31-19,1050 Boyles St,POB B, Frederick, MD 21702 USA.
EM chenxin@mail.nih.gov
RI Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
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 HHSN261200800001E. This research was supported [in part] by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 42
TC 8
Z9 8
U1 2
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD JAN
PY 2014
VL 65
IS 1
BP 56
EP 64
DI 10.1016/j.cyto.2013.09.008
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 275YU
UT WOS:000328716100009
PM 24080164
ER
PT J
AU Zhao, YG
Flandin, P
Vogt, D
Blood, A
Hermesz, E
Westphal, H
Rubenstein, JLR
AF Zhao, Yangu
Flandin, Pierre
Vogt, Daniel
Blood, Alexander
Hermesz, Edit
Westphal, Heiner
Rubenstein, John L. R.
TI Ldb1 is essential for development of Nkx2.1 lineage derived GABAergic
and cholinergic neurons in the telencephalon
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Differentiation; Forebrain development; Interneuron; Mouse; Tangential
migration
ID LIM-HOMEOBOX GENE; HOMEODOMAIN PROTEINS; TRANSCRIPTION FACTOR; STRIATAL
INTERNEURONS; SPECIFICATION; FOREBRAIN; LHX6; MIGRATION; SUBTYPES;
PROGENITORS
AB The progenitor zones of the embryonic mouse ventral telencephalon give rise to GABAergic and cholinergic neurons. We have shown previously that two LIM-homeodomain (LIM-HD) transcription factors, Lhx6 and Lhx8, that are downstream of Nkx2.1, are critical for the development of telencephalic GABAergic and cholinergic neurons. Here we investigate the role of Ldb1, a nuclear protein that binds directly to all LIM-HD factors, in the development of these ventral telencephalon derived neurons. We show that Ldb1 is expressed in the Nkx2.1 cell lineage during embryonic development and in mature neurons. Conditional deletion of Ldb1 causes defects in the expression of a series of genes in the ventral telencephalon and severe impairment in the tangential migration of cortical intemeurons from the ventral telencephalon. Similar to the phenotypes observed in Lhx6 or Lhx8 mutant mice, the Ldb1 conditional mutants show a reduction in the number of both GABAergic and cholinergic neurons in the telencephalon. Furthermore, our analysis reveals defects in the development of the parvalbumin-positive neurons in the globus pallidus and striatum of the Ldb1 mutants. These results provide evidence that Ldb1 plays an essential role as a transcription co-regulator of Lhx6 and Lhx8 in the control of mammalian telencephalon development. Published by Elsevier Inc.
C1 [Zhao, Yangu; Blood, Alexander; Hermesz, Edit; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Genom Differentiat, Bethesda, MD 20892 USA.
[Flandin, Pierre; Vogt, Daniel; Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Flandin, Pierre; Vogt, Daniel; Rubenstein, John L. R.] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94143 USA.
RP Zhao, YG (reprint author), NIDDK NIH, Room 3130,Building 50,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM zhaoyang@mail.nih.gov; john.rubenstein@ucsf.edu
OI Vogt, Daniel/0000-0003-1876-5936
FU Nina Ireland; Weston Havens Foundation [NIMH R01 MH081880, NIMH R37
MH049428]; NIH intramural research program
FX We would like to thank Dr. Stewart Anderson for sharing the Nkx2.1-Cre
mice, and Drs. Liqi Li and Paul Love for sharing the Ldb1 antibody. This
work was supported by the research grants to JLRR from Nina Ireland,
Weston Havens Foundation, NIMH R01 MH081880, and NIMH R37 MH049428, and
funds from the NIH intramural research program to HW. The authors
declare no competing financial interests.
NR 29
TC 5
Z9 6
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD JAN 1
PY 2014
VL 385
IS 1
BP 94
EP 106
DI 10.1016/j.ydbio.2013.10.010
PG 13
WC Developmental Biology
SC Developmental Biology
GA 277CN
UT WOS:000328796100010
PM 24157949
ER
PT J
AU El-Gohary, Y
Tulachan, S
Wiersch, J
Guo, P
Welsh, C
Prasadan, K
Paredes, J
Shiota, C
Xiao, XW
Wada, Y
Diaz, M
Gittes, G
AF El-Gohary, Yousef
Tulachan, Sidhartha
Wiersch, John
Guo, Ping
Welsh, Carey
Prasadan, Krishna
Paredes, Jose
Shiota, Chiyo
Xiao, Xiangwei
Wada, Yoko
Diaz, Marilyn
Gittes, George
TI A Smad Signaling Network Regulates Islet Cell Proliferation
SO DIABETES
LA English
DT Article
ID PANCREATIC BETA-CELLS; ENDOCRINE PANCREAS; EXOCRINE PANCREAS;
MESENCHYMAL TRANSITION; DIFFERENTIAL ROLES; PRECURSOR CELLS; MOUSE
PANCREAS; AR42J CELLS; IN-VITRO; GROWTH
AB Pancreatic -cell loss and dysfunction are critical components of all types of diabetes. Human and rodent -cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor- (TGF-) signaling has been shown to affect -cell development, proliferation, and function, but -cell proliferation is thought to be the only source of new -cells in the adult. Recently, -cell dedifferentiation has been shown to be an important contributory mechanism to -cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF- regulators, smads 7, 2, and 3, control -cell proliferation after -cell loss, and specifically, smad7 is necessary for that -cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of -cells to a pancreatic polypeptide-fold hormone-positive state. TGF- receptor II appears to be a receptor important for controlling the status of the smad network in -cells. These studies should help our understanding of properly regulated -cell replication.
C1 [El-Gohary, Yousef; Wiersch, John; Guo, Ping; Prasadan, Krishna; Paredes, Jose; Shiota, Chiyo; Xiao, Xiangwei; Gittes, George] Childrens Hosp Pittsburgh, Dept Surg, Div Pediat Surg, Pittsburgh, PA 15213 USA.
[Tulachan, Sidhartha] St Elizabeth Hlth Ctr, Dept Internal Med, Youngstown, OH USA.
[Wiersch, John] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Surg, San Antonio, TX 78229 USA.
[Welsh, Carey] Childrens Hosp Pittsburgh, Dept Pediat, Div Neonatol, Pittsburgh, PA 15213 USA.
[Wada, Yoko] Niigata Univ, Grad Sch Med & Dent Sci, Div Clin Nephrol & Rheumatol, Niigata, Japan.
[Diaz, Marilyn] Natl Inst Environm Hlth Sci, Lab Mol Genet, NIH, Res Triangle Pk, NC USA.
RP Gittes, G (reprint author), Childrens Hosp Pittsburgh, Dept Surg, Div Pediat Surg, Pittsburgh, PA 15213 USA.
EM george.gittes@chp.edu
FU National Institutes of Health [R01-DK-064952, R01-DK-083541-01];
Children's Hospital of Pittsburgh; Division of Intramural Research of
the National Institutes of Health (National Institute of Environmental
Health Sciences) [Z01-ES-101603]
FX This study was supported by the National Institutes of Health (grants
R01-DK-064952 and R01-DK-083541-01 to G. G.), and the Children's
Hospital of Pittsburgh. M. D. was supported by Project Z01-ES-101603
from the Division of Intramural Research of the National Institutes of
Health (National Institute of Environmental Health Sciences).
NR 50
TC 27
Z9 27
U1 2
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD JAN
PY 2014
VL 63
IS 1
BP 224
EP 236
DI 10.2337/db13-0432
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 275MF
UT WOS:000328680400029
PM 24089514
ER
PT J
AU Hanson, RL
Muller, YL
Kobes, S
Guo, TW
Bian, L
Ossowski, V
Wiedrich, K
Sutherland, J
Wiedrich, C
Mahkee, D
Huang, K
Abdussamad, M
Traurig, M
Weil, EJ
Nelson, RG
Bennett, PH
Knowler, WC
Bogardus, C
Baier, LJ
AF Hanson, Robert L.
Muller, Yunhua L.
Kobes, Sayuko
Guo, Tingwei
Bian, Li
Ossowski, Victoria
Wiedrich, Kim
Sutherland, Jeffrey
Wiedrich, Christopher
Mahkee, Darin
Huang, Ke
Abdussamad, Maryam
Traurig, Michael
Weil, E. Jennifer
Nelson, Robert G.
Bennett, Peter H.
Knowler, William C.
Bogardus, Clifton
Baier, Leslie J.
TI A Genome-Wide Association Study in American Indians Implicates DNER as a
Susceptibility Locus for Type 2 Diabetes
SO DIABETES
LA English
DT Article
ID INSULIN-RESISTANCE; PLASMA-GLUCOSE; PIMA-INDIANS; VARIANTS; MELLITUS;
RISK; POPULATIONS; LINKAGE; ORIGIN; ONSET
AB Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls 45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a approximate to 1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 x 10(-8), which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic -cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.
C1 [Hanson, Robert L.; Muller, Yunhua L.; Kobes, Sayuko; Guo, Tingwei; Bian, Li; Ossowski, Victoria; Wiedrich, Kim; Sutherland, Jeffrey; Wiedrich, Christopher; Mahkee, Darin; Huang, Ke; Abdussamad, Maryam; Traurig, Michael; Weil, E. Jennifer; Nelson, Robert G.; Bennett, Peter H.; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
RP Hanson, RL (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
EM rhanson@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases;
American Diabetes Association [7-04-DCS-02]
FX This work was supported, in part, by the intramural research program of
the National Institute of Diabetes and Digestive and Kidney Diseases
and, in part, by an award (7-04-DCS-02) to C.B. from the American
Diabetes Association.
NR 25
TC 22
Z9 23
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD JAN
PY 2014
VL 63
IS 1
BP 369
EP 376
DI 10.2337/db13-0416
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 275MF
UT WOS:000328680400043
PM 24101674
ER
PT J
AU Larson, NB
Jenkins, GD
Larson, MC
Vierkant, RA
Sellers, TA
Phelan, CM
Schildkraut, JM
Sutphen, R
Pharoah, PPD
Gayther, SA
Wentzensen, N
Goode, EL
Fridley, BL
AF Larson, Nicholas B.
Jenkins, Gregory D.
Larson, Melissa C.
Vierkant, Robert A.
Sellers, Thomas A.
Phelan, Catherine M.
Schildkraut, Joellen M.
Sutphen, Rebecca
Pharoah, Paul P. D.
Gayther, Simon A.
Wentzensen, Nicolas
Goode, Ellen L.
Fridley, Brooke L.
CA Ovarian Canc Association Consortiu
TI Kernel canonical correlation analysis for assessing gene-gene
interactions and application to ovarian cancer
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE association studies; canonical correlation; gene-gene interaction;
kernel methods
ID GENOME-WIDE ASSOCIATION; PRINCIPAL-COMPONENTS; GENOTYPE DATA;
HUMAN-DISEASE; VARIANTS; RISK; SUSCEPTIBILITY; SEQUENCE; TESTS; MODEL
AB Although single-locus approaches have been widely applied to identify disease-associated single-nucleotide polymorphisms (SNPs), complex diseases are thought to be the product of multiple interactions between loci. This has led to the recent development of statistical methods for detecting statistical interactions between two loci. Canonical correlation analysis (CCA) has previously been proposed to detect gene-gene coassociation. However, this approach is limited to detecting linear relations and can only be applied when the number of observations exceeds the number of SNPs in a gene. This limitation is particularly important for next-generation sequencing, which could yield a large number of novel variants on a limited number of subjects. To overcome these limitations, we propose an approach to detect gene-gene interactions on the basis of a kernelized version of CCA (KCCA). Our simulation studies showed that KCCA controls the Type-I error, and is more powerful than leading gene-based approaches under a disease model with negligible marginal effects. To demonstrate the utility of our approach, we also applied KCCA to assess interactions between 200 genes in the NF-kappa B pathway in relation to ovarian cancer risk in 3869 cases and 3276 controls. We identified 13 significant gene pairs relevant to ovarian cancer risk (local false discovery rate <0.05). Finally, we discuss the advantages of KCCA in gene-gene interaction analysis and its future role in genetic association studies.
C1 [Larson, Nicholas B.; Jenkins, Gregory D.; Larson, Melissa C.; Vierkant, Robert A.; Goode, Ellen L.; Fridley, Brooke L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Sellers, Thomas A.; Phelan, Catherine M.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Schildkraut, Joellen M.] Duke Univ, Duke Comprehens Canc Ctr, Durham, NC USA.
[Sutphen, Rebecca] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA.
[Pharoah, Paul P. D.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Gayther, Simon A.] Univ So Calif, Dept Preventat Med, Los Angeles, CA USA.
[Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA.
RP Fridley, BL (reprint author), Univ Kansas, Med Ctr, Dept Biostat, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM bfridley@kumc.edu
RI Fridley, Brooke/D-8315-2015
OI Fridley, Brooke/0000-0001-7739-7956
FU Minnesota Partnership for Biotechnology and Medical Genomics; Mayo
Foundation; Fred C and Katherine B Andersen Foundation, the Cambridge
Biomedical Research Centre; Cancer Research UK [C490/A10119]; Celma
Mastry Ovarian Cancer Foundation; US National Institutes of Health
[CA168524, CA106414, CA136393, CA122443, CA114343, CA140879, GM86689];
Genetic Associations and Mechanisms in Oncology (GAME-ON), a NCI Cancer
Post-GWAS Initiative [U19-CA148112]
FX This study was funded by the Minnesota Partnership for Biotechnology and
Medical Genomics; the Mayo Foundation; the Fred C and Katherine B
Andersen Foundation, the Cambridge Biomedical Research Centre; Cancer
Research UK (C490/A10119); the Celma Mastry Ovarian Cancer Foundation;
and the US National Institutes of Health (CA168524, CA106414, CA136393,
CA122443, CA114343, CA140879, and GM86689). The scientific development
and funding for this project were partly supported by Genetic
Associations and Mechanisms in Oncology (GAME-ON), a NCI Cancer
Post-GWAS Initiative (U19-CA148112).
NR 35
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U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JAN
PY 2014
VL 22
IS 1
BP 126
EP 131
DI 10.1038/ejhg.2013.69
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 275PP
UT WOS:000328689600026
PM 23591404
ER
PT J
AU Ramos, EM
Hoffman, D
Junkins, HA
Maglott, D
Phan, L
Sherry, ST
Feolo, M
Hindorff, LA
AF Ramos, Erin M.
Hoffman, Douglas
Junkins, Heather A.
Maglott, Donna
Phan, Lon
Sherry, Stephen T.
Feolo, Mike
Hindorff, Lucia A.
TI Phenotype-Genotype Integrator (PheGenI): synthesizing genome- wide
association study (GWAS) data with existing genomic resources
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE database; data integration; genome sequence; genome-wide association
study; phenotype; single nucleotide polymorphism
AB Rapidly accumulating data from genome-wide association studies (GWASs) and other large-scale studies are most useful when synthesized with existing databases. To address this opportunity, we developed the Phenotype-Genotype Integrator (PheGenI), a user-friendly web interface that integrates various National Center for Biotechnology Information (NCBI) genomic databases with association data from the National Human Genome Research Institute GWAS Catalog and supports downloads of search results. Here, we describe the rationale for and development of this resource. Integrating over 66 000 association records with extensive single nucleotide polymorphism (SNP), gene, and expression quantitative trait loci data already available from the NCBI, PheGenI enables deeper investigation and interrogation of SNPs associated with a wide range of traits, facilitating the examination of the relationships between genetic variation and human diseases.
C1 [Ramos, Erin M.; Junkins, Heather A.; Hindorff, Lucia A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Hoffman, Douglas; Maglott, Donna; Phan, Lon; Sherry, Stephen T.; Feolo, Mike] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20814 USA.
RP Feolo, M (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 45,4AN-12B, Bethesda, MD 20814 USA.
EM feolo@ncbi.nlm.nih.gov
FU Intramural Research Program of the US National Institutes of Health,
National Library of Medicine
FX We thank M Kimura, J Paschall, and T Manolio for thoughtful input
throughout the development of PheGenI. This research was supported, in
part, by the Intramural Research Program of the US National Institutes
of Health, National Library of Medicine.
NR 5
TC 29
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U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JAN
PY 2014
VL 22
IS 1
BP 144
EP 147
DI 10.1038/ejhg.2013.96
PG 4
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 275PP
UT WOS:000328689600030
PM 23695286
ER
PT J
AU Yu, IW
Espinoza, DA
McAlexander, MA
Witwer, KW
AF Yu, Ian W.
Espinoza, Diego A.
McAlexander, Melissa A.
Witwer, Kenneth W.
TI OpenArray profiling reveals no differential modulation of miRNA by
positive and negative CD4(+) T cell immunoselection
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Letter
ID LYMPHOCYTES; EXPRESSION; MICRORNA
C1 [Yu, Ian W.; Espinoza, Diego A.; McAlexander, Melissa A.; Witwer, Kenneth W.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
[Yu, Ian W.] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA.
RP Witwer, KW (reprint author), 733 N Broadway,Miller Res Bldg Rm 829, Baltimore, MD 21205 USA.
EM kwitwer1@jhmi.edu
RI Witwer, Kenneth/G-1626-2013
OI Witwer, Kenneth/0000-0003-1664-4233
FU NIAID NIH HHS [R21 AI102659, R21AI102659]; NIMH NIH HHS [P30 MH075673];
NINDS NIH HHS [R01 NS076357, R01NS076357]; PHS HHS [P30 MHO75673]
NR 10
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
EI 1873-2399
J9 EXP HEMATOL
JI Exp. Hematol.
PD JAN
PY 2014
VL 42
IS 1
BP 11
EP 13
DI 10.1016/j.exphem.2013.09.011
PG 3
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 275DN
UT WOS:000328656600002
PM 24096121
ER
PT J
AU Raghavachari, N
Liu, PC
Barb, JJ
Yang, YQ
Wang, R
Nguyen, QT
Munson, PJ
AF Raghavachari, Nalini
Liu, Poching
Barb, Jennifer J.
Yang, Yanqin
Wang, Richard
Quang Tri Nguyen
Munson, Peter J.
TI Integrated analysis of miRNA and mRNA during differentiation of human
CD34(+) cells delineates the regulatory roles of microRNA in
hematopoiesis
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID EXPRESSION PROFILES; STEM-CELLS; ERYTHROPOIESIS; MEGAKARYOPOIESIS;
PROGENITOR; PREDICTION; ANIMALS; TARGETS; LOOP
AB In the process of human hematopoiesis, precise regulation of the expression of lineage-specific gene products is critical for multiple cell-fate decisions that govern cell differentiation, proliferation, and self-renewal. Given the important role of microRNAs (miRNAs) in development and differentiation, we examined the global expression of miRNA in CD34(+) cells during lineage specific hematopoiesis and found 49 miRNAs to be differentially expressed, with functional roles in cellular growth and proliferation, and apoptosis. miR-18a was upregulated during erythropoiesis and downregulated during megakaryopoiesis. miR-145 was upregulated during granulopoiesis and down regulated during erythropoiesis. Megakaryopoitic differentiation resulted in significant alteration in the expression of many miRNAs that are believed to play critical roles in the regulation of B and T cell differentiation. Target prediction analyses on three different miRNA databases indicated that TargetScan outperformed microCosm and miRDB in identifying potential miRNA targets associated with hematopoietic differentiation process. An integrated analysis of the observed miRNAs and messenger RNAs (mRNAs) resulted in 87 highly correlated miRNA-mRNA pairs that have major functional roles in cellular growth and proliferation, hematopoietic system development, and Wnt/B-catenin and Flt 3 signaling pathways. We believe that this study will enhance our understanding on the regulatory roles of miRNA in hematopoiesis by providing a library of mRNA-miRNA networks. Published by Elsevier Inc. on behalf of ISEH - Society for Hematology and Stem Cells.
C1 [Raghavachari, Nalini; Barb, Jennifer J.; Yang, Yanqin; Wang, Richard] NHLBI, Genom Core Facil, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NIH, Bethesda, MD 20892 USA.
[Liu, Poching; Quang Tri Nguyen; Munson, Peter J.] Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD USA.
RP Raghavachari, N (reprint author), NIA, Div Geriatr & Clin Gerontol, Gateway Bldg,Suite 3C307,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM Nalini.raghavachari@nih.gov
FU Intramural Research, National Heart, Lung, and Blood Institute
FX This work was funded by Intramural Research, National Heart, Lung, and
Blood Institute. We thank Harry L. Malech and Uimook Choi, in Genetic
Immunotherapy Section, Laboratory of Host Defenses, National Institute
of Allergy and Infectious Diseases, National Institutes of Health, for
providing the CD34+ cells; Leigh Samsel in the NHLBI Flow
Cytometry Core for help with the flow characterization of cells; Cuhur
Yusuf Demirkale for his helpful suggestions in data analysis; and Ms.
Bandana Prasad at Strand Life Sciences, Bangalore (Agilent Technologies'
partner) for help with TargetScan analysis.
NR 50
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U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
EI 1873-2399
J9 EXP HEMATOL
JI Exp. Hematol.
PD JAN
PY 2014
VL 42
IS 1
BP 14
EP 27
DI 10.1016/j.exphem.2013.10.003
PG 14
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 275DN
UT WOS:000328656600003
PM 24139908
ER
PT J
AU Brady, LS
Potter, WZ
AF Brady, Linda S.
Potter, William Z.
TI Public-private partnerships to revitalize psychiatric drug discovery
SO EXPERT OPINION ON DRUG DISCOVERY
LA English
DT Editorial Material
DE Alzheimer's Disease Neuroimaging Initiative; autism spectrum disorder;
biomarkers; Biomarkers Consortium; cellular models; consortia; disease
phenotyping; major depressive disorder; psychiatric drug discovery;
psychiatric genetics; public-private partnerships; schizophrenia
ID THERAPEUTICS DISCOVERY; DISORDERS; DISEASE
AB Introduction: Precompetitive public-private partnerships (PPPs) have the potential to improve psychiatric drug discovery by addressing gaps in the research and development pipeline such as the identification and validation of new targets, models, biomarkers and disease phenotyping. PPPs are a model to strategically bring together expertise, in-kind support and funding from multiple public and private sector partners.
Areas covered: This editorial describes selected case examples of established and emerging public-private consortia in the United States and Europe that provide tools, methods or resources to accelerate central nervous system (CNS) drug discovery. The authors provides a listing of public-private consortia projects that focus on the CNS, the stage of the drug discovery pipeline that they address, diseases, deliverables provided and current consortia partners.
Expert opinion: Some of the projects undertaken by PPPs in the area of CNS drug discovery and development are beginning to make tools, resources and data publicly available. Only a few PPPs have delivered enough to extract lessons learned. These include building alignment across a wide group of stakeholders, engaging advocacy groups and funding commitments for a minimum of 5 years.
C1 [Brady, Linda S.] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
[Potter, William Z.] NIMH, Bethesda, MD 20892 USA.
RP Brady, LS (reprint author), NIMH, Div Neurosci & Basic Behav Sci, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM lbrady@mail.nih.gov
NR 18
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U1 0
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1746-0441
EI 1746-045X
J9 EXPERT OPIN DRUG DIS
JI Expert. Opin. Drug Discov.
PD JAN
PY 2014
VL 9
IS 1
BP 1
EP 8
DI 10.1517/17460441.2014.867944
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 274CM
UT WOS:000328582700001
PM 24308355
ER
PT J
AU Towner, PH
AF Towner, Philip H.
TI 1 & 2 Timothy and Titus
SO EXPOSITORY TIMES
LA English
DT Book Review
C1 [Towner, Philip H.] Nida Inst Bibl Scholarship, New York, NY 10023 USA.
RP Towner, PH (reprint author), Nida Inst Bibl Scholarship, New York, NY 10023 USA.
NR 1
TC 0
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U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0014-5246
EI 1745-5308
J9 EXPOSITORY TIMES
JI Exposit. Times
PD JAN
PY 2014
VL 125
IS 4
BP 204
EP 205
DI 10.1177/0014524613494634n
PG 2
WC Religion
SC Religion
GA 276HU
UT WOS:000328741400025
ER
PT J
AU Logsdon, BA
Dai, JY
Auer, PL
Johnsen, JM
Ganesh, SK
Smith, NL
Wilson, JG
Tracy, RP
Lange, LA
Jiao, S
Rich, SS
Lettre, G
Carlson, CS
Jackson, RD
O'Donnell, CJ
Wurfel, MM
Nickerson, DA
Tang, H
Reiner, AP
Kooperberg, C
AF Logsdon, Benjamin A.
Dai, James Y.
Auer, Paul L.
Johnsen, Jill M.
Ganesh, Santhi K.
Smith, Nicholas L.
Wilson, James G.
Tracy, Russell P.
Lange, Leslie A.
Jiao, Shuo
Rich, Stephen S.
Lettre, Guillaume
Carlson, Christopher S.
Jackson, Rebecca D.
O'Donnell, Christopher J.
Wurfel, Mark M.
Nickerson, Deborah A.
Tang, Hua
Reiner, Alexander P.
Kooperberg, Charles
CA NHLBI GO Exome Sequencing Project
TI A Variational Bayes Discrete Mixture Test for Rare Variant Association
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE Exome sequencing study; approximate inference; von Willebrand Factor
genetics
ID VON-WILLEBRAND-FACTOR; GENOME-WIDE ASSOCIATION; EXOME SEQUENCING
PROJECT; GENETIC ASSOCIATION; MISSING HERITABILITY; DISEASE ASSOCIATION;
AFRICAN-AMERICANS; COMMON DISEASES; FACTOR-VIII; RISK
AB Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that aggregate tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (approximate to 10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.
C1 [Logsdon, Benjamin A.; Dai, James Y.; Auer, Paul L.; Carlson, Christopher S.; Reiner, Alexander P.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Logsdon, Benjamin A.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Dai, James Y.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Johnsen, Jill M.] Puget Sound Blood Ctr, Inst Res, Seattle, WA 98104 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Smith, Nicholas L.; Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, VA Off Res & Dev, Seattle, WA USA.
[Wilson, James G.] Univ Mississippi Med Ctr, Dept Physiol & Biophys, Jackson, MS USA.
[Tracy, Russell P.] Univ Vermont Coll Med, Dept Pathol & Biochem, Burlington, VT USA.
[Lange, Leslie A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet & Biostat, Chapel Hill, NC USA.
[Lange, Leslie A.] Univ N Carolina, Dept Bioinformat, Chapel Hill, NC USA.
[Lange, Leslie A.] Univ N Carolina, Dept Computat Biol, Chapel Hill, NC USA.
[Jiao, Shuo] Fred Hutchinson Canc Res Ctr, Cancer Prevent Program, Seattle, WA 98104 USA.
[Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
[Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst Ctr Populat Studies, Framingham, MA USA.
[Wurfel, Mark M.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Tang, Hua] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
[Tang, Hua] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Johnsen, Jill M.] Univ Washington, Dept Med, Seattle, WA USA.
[Auer, Paul L.] Univ Wisconsin Milwaukee, Sch Publ Hlth, Milwaukee, WI USA.
RP Logsdon, BA (reprint author), Univ Washington, Box 352350, Seattle, WA 98195 USA.
EM blogsdon@uw.edu
FU NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2
HL-102926]; National Institute of Health [R01 HG-006124, P01 CA-53996,
R01 HL-114901]; National Heart, Lung, and Blood Institute (NHLBI)
FX The authors wish to acknowledge the support of the National Heart, Lung,
and Blood Institute (NHLBI) and the contributions of the research
institutions, study investigators, field staff, and study participants
in creating this resource for biomedical research. Funding for GO ESP
was provided by NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923
(LungGO) and RC2 HL-102924 (WHISP). The exome sequencing was performed
through NHLBI grants RC2 HL-102925 (BroadGO) and RC2 HL-102926
(SeattleGO). In addition, this research was supported by National
Institute of Health grants R01 HG-006124, P01 CA-53996, and R01
HL-114901.
NR 50
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U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JAN
PY 2014
VL 38
IS 1
BP 21
EP 30
DI 10.1002/gepi.21772
PG 10
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 272LW
UT WOS:000328463200003
PM 24482836
ER
PT J
AU Schoeps, A
Rudolph, A
Seibold, P
Dunning, AM
Milne, RL
Bojesen, SE
Swerdlow, A
Andrulis, I
Brenner, H
Behrens, S
Orr, N
Jones, M
Ashworth, A
Li, JM
Cramp, H
Connley, D
Czene, K
Darabi, H
Chanock, SJ
Lissowska, J
Figueroa, JD
Knight, J
Glendon, G
Mulligan, AM
Dumont, M
Severi, G
Baglietto, L
Olson, J
Vachon, C
Purrington, K
Moisse, M
Neven, P
Wildiers, H
Spurdle, A
Kosma, VM
Kataja, V
Hartikainen, JM
Hamann, U
Ko, YD
Dieffenbach, AK
Arndt, V
Stegmaier, C
Malats, N
Perez, JIA
Benitez, J
Flyger, H
Nordestgaard, BG
Truong, T
Cordina-Duverger, E
Menegaux, F
Silva, ID
Fletcher, O
Johnson, N
Haberle, L
Beckmann, MW
Ekici, AB
Braaf, L
Atsma, F
van den Broek, AJ
Makalic, E
Schmidt, DF
Southey, MC
Cox, A
Simard, J
Giles, GG
Lambrechts, D
Mannermaa, A
Brauch, H
Guenel, P
Peto, J
Fasching, PA
Hopper, J
Flesch-Janys, D
Couch, F
Chenevix-Trench, G
Pharoah, PDP
Garcia-Closas, M
Schmidt, MK
Hall, P
Easton, DF
Chang-Claude, J
AF Schoeps, Anja
Rudolph, Anja
Seibold, Petra
Dunning, Alison M.
Milne, Roger L.
Bojesen, Stig E.
Swerdlow, Anthony
Andrulis, Irene
Brenner, Hermann
Behrens, Sabine
Orr, Nicholas
Jones, Michael
Ashworth, Alan
Li, Jingmei
Cramp, Helen
Connley, Dan
Czene, Kamila
Darabi, Hatef
Chanock, Stephen J.
Lissowska, Jolanta
Figueroa, Jonine D.
Knight, Julia
Glendon, Gord
Mulligan, Anna M.
Dumont, Martine
Severi, Gianluca
Baglietto, Laura
Olson, Janet
Vachon, Celine
Purrington, Kristen
Moisse, Matthieu
Neven, Patrick
Wildiers, Hans
Spurdle, Amanda
Kosma, Veli-Matti
Kataja, Vesa
Hartikainen, Jaana M.
Hamann, Ute
Ko, Yon-Dschun
Dieffenbach, Aida K.
Arndt, Volker
Stegmaier, Christa
Malats, Nuria
Arias Perez, Jose I.
Benitez, Javier
Flyger, Henrik
Nordestgaard, Borge G.
Truong, Therese
Cordina-Duverger, Emilie
Menegaux, Florence
dos Santos Silva, Isabel
Fletcher, Olivia
Johnson, Nichola
Haeberle, Lothar
Beckmann, Matthias W.
Ekici, Arif B.
Braaf, Linde
Atsma, Femke
van den Broek, Alexandra J.
Makalic, Enes
Schmidt, Daniel F.
Southey, Melissa C.
Cox, Angela
Simard, Jacques
Giles, Graham G.
Lambrechts, Diether
Mannermaa, Arto
Brauch, Hiltrud
Guenel, Pascal
Peto, Julian
Fasching, Peter A.
Hopper, John
Flesch-Janys, Dieter
Couch, Fergus
Chenevix-Trench, Georgia
Pharoah, Paul D. P.
Garcia-Closas, Montserrat
Schmidt, Marjanka K.
Hall, Per
Easton, Douglas F.
Chang-Claude, Jenny
TI Identification of New Genetic Susceptibility Loci for Breast Cancer
Through Consideration of Gene-Environment Interactions
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE breast cancer risk; gene-environment interaction; polymorphisms; body
mass index; case-control study
ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; HORMONE-THERAPY; RISK-FACTORS;
FGFR2 GENE; METAANALYSIS; VARIANTS; FAMILY; COHORT; WOMEN
AB Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G x E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 x 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 x 10(-05)). Our findings confirm comparable power of the recent methods for detecting G x E interaction and the utility of using G x E interaction analyses to identify new susceptibility loci.
C1 [Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Behrens, Sabine; Chang-Claude, Jenny] German Canc Res Ctr, Dept Canc Epidemiol, D-69120 Heidelberg, Germany.
[Schoeps, Anja] Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany.
[Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Milne, Roger L.; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
[Bojesen, Stig E.; Jones, Michael; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
[Swerdlow, Anthony] Inst Canc Res, Dept Genet & Epidemiol, Sutton, Surrey, England.
[Andrulis, Irene] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Dept Mol Genet, Toronto, ON M5G 1X5, Canada.
[Brenner, Hermann; Dieffenbach, Aida K.; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann; Dieffenbach, Aida K.] German Canc Consortium, Heidelberg, Germany.
[Orr, Nicholas] Inst Canc Res, Dept Breast Canc Res, London SW3 6JB, England.
[Ashworth, Alan; Li, Jingmei] Genome Inst Singapore, Dept Human Genet, Singapore, Singapore.
[Cramp, Helen; Connley, Dan; Cox, Angela] Univ Sheffield, Inst Canc Studies, Dept Oncol, Sheffield, S Yorkshire, England.
[Czene, Kamila; Darabi, Hatef; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Chanock, Stephen J.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Knight, Julia] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Knight, Julia; Glendon, Gord] Prosserman Ctr Hlth Res, Toronto, ON, Canada.
[Mulligan, Anna M.] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Dumont, Martine; Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Canc Genom Lab, Quebec City, PQ, Canada.
[Dumont, Martine; Simard, Jacques] Univ Laval, Fac Med, Dept Mol Med, Quebec City, PQ G1K 7P4, Canada.
[Severi, Gianluca; Baglietto, Laura; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Baglietto, Laura; Schmidt, Daniel F.; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Olson, Janet; Vachon, Celine; Purrington, Kristen] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Moisse, Matthieu; Lambrechts, Diether] VIB, VRC, Flanders, Belgium.
[Moisse, Matthieu; Lambrechts, Diether] Univ Louvain, Dept Oncol, Lab Translat Genet, Louvain, Belgium.
[Neven, Patrick; Wildiers, Hans] Univ Hosp Gasthuisberg, Dept Multidisciplinary Breast Canc, B-3000 Louvain, Belgium.
[Spurdle, Amanda; Chenevix-Trench, Georgia] Queensland Inst Med Res, Dept Mol Canc Epidemiol, Brisbane, Qld 4006, Australia.
[Kosma, Veli-Matti; Kataja, Vesa] Univ Kuopio, Dept Pathol, Kuopio, Finland.
[Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med, Kuopio, Finland.
[Hamann, Ute] German Canc Res Ctr, Div Mol Genet Breast Canc, Heidelberg, Germany.
[Ko, Yon-Dschun] Johanniter Krankenhaus, Evangel Kliniken Bonn GmbH, Dept Internal Med, Bonn, Germany.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Arias Perez, Jose I.] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Benitez, Javier] Spanish Natl Canc Reserach Ctr CNIO, Human Genet Grp, Madrid, Spain.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark.
[Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence; Guenel, Pascal] Univ Paris Sud, UMRS 1018, Villejuif, France.
[Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence; Guenel, Pascal] CESP Ctr Res Epidemiol & Populat Hlth, INSERM, U1018, Villejuif, France.
[dos Santos Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommun Dis Epidemiol, London WC1, England.
[Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Haeberle, Lothar; Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Braaf, Linde; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands.
[Braaf, Linde; van den Broek, Alexandra J.; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
[Atsma, Femke] Sanquin Nijmegen, Dept Donor Studies, Nijmegen, Netherlands.
[Makalic, Enes] Univ Melbourne, Dept Analyt Epidemiol, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Mannermaa, Arto] Univ Kuopio, Kuopio Univ Hosp, Dept Pathol & Forens Med, FIN-70211 Kuopio, Finland.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharamcol, Stuttgart, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Hopper, John] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Couch, Fergus] Mayo Clin, Dept Expt Pathol, Rochester, MN USA.
[Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol & Publ Hlth & Primary Care, Cambridge, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Genet & Epidemiol, London SW3 6JB, England.
[Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Chang-Claude, J (reprint author), German Canc Res Ctr, Dept Canc Epidemiol, Neuenheimer Feld 581, D-69120 Heidelberg, Germany.
EM j.chang-claude@dkfz.de
RI Li, Jingmei/I-2904-2012; Malats, Nuria/H-7041-2015; Atsma,
F./L-4178-2015; Brenner, Hermann/B-4627-2017; Spurdle,
Amanda/A-4978-2011; Andrulis, Irene/E-7267-2013; Hartikainen,
Jaana/E-6256-2015; Garcia-Closas, Montserrat /F-3871-2015
OI Dunning, Alison Margaret/0000-0001-6651-7166; Giles,
Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684; Li,
Jingmei/0000-0001-8587-7511; Malats, Nuria/0000-0003-2538-3784; Brenner,
Hermann/0000-0002-6129-1572; Czene, Kamila/0000-0002-3233-5695; Spurdle,
Amanda/0000-0003-1337-7897; Lissowska, Jolanta/0000-0003-2695-5799; Cox,
Angela/0000-0002-5138-1099; Moisse, Matthieu/0000-0001-8880-9311;
Garcia-Closas, Montserrat /0000-0003-1033-2650
FU European Community [223175]; Cancer Research UK [C1287/A10118, C1287/A
10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007,
C5047/A10692]; National Institutes of Health [CA128978]; Post-Cancer
GWAS initiative (the GAME-ON initiative) [1U19 CA148537, 1U19 CA148065,
1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian
Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks
of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research
Foundation; Ovarian Cancer Research Fund
FX Funding for the iCOGS infrastructure came from the European Community's
Seventh Framework Programme under grant agreement 223175
(HEALTH-F2-2009-223175, COGS), Cancer Research UK (C1287/A10118, C1287/A
10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007,
C5047/A10692), the National Institutes of Health (CA128978), and
Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19
CA148112-the GAME-ON initiative), the Department of Defence
(W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR)
for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation
for the Cure, the Breast Cancer Research Foundation, and the Ovarian
Cancer Research Fund.
NR 47
TC 11
Z9 11
U1 4
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JAN
PY 2014
VL 38
IS 1
BP 84
EP 93
DI 10.1002/gepi.21771
PG 10
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 272LW
UT WOS:000328463200009
PM 24248812
ER
PT J
AU He, MA
Wu, C
Xu, JF
Guo, H
Yang, HD
Zhang, XM
Sun, JL
Yu, DK
Zhou, L
Peng, T
He, YF
Gao, Y
Yuan, J
Deng, QF
Dai, XY
Tan, AH
Feng, YY
Zhang, HY
Min, XW
Yang, XB
Zhu, J
Zhai, K
Chang, J
Qin, X
Tan, W
Hu, YL
Lang, MJ
Tao, S
Li, YF
Li, Y
Feng, JJ
Li, DF
Kim, ST
Zhang, SJ
Zhang, HX
Zheng, SL
Gui, LX
Wang, YJ
Wei, S
Wang, F
Fang, WM
Liang, Y
Zhai, Y
Chen, WH
Miao, XP
Zhou, GQ
Hu, FB
Lin, DX
Mo, ZN
Wu, TC
AF He, Meian
Wu, Chen
Xu, Jianfeng
Guo, Huan
Yang, Handong
Zhang, Xiaomin
Sun, Jielin
Yu, Dianke
Zhou, Li
Peng, Tao
He, Yunfeng
Gao, Yong
Yuan, Jing
Deng, Qifei
Dai, Xiayun
Tan, Aihua
Feng, Yingying
Zhang, Haiying
Min, Xinwen
Yang, Xiaobo
Zhu, Jiang
Zhai, Kan
Chang, Jiang
Qin, Xue
Tan, Wen
Hu, Yanling
Lang, Mingjian
Tao, Sha
Li, Yuanfeng
Li, Yi
Feng, Junjie
Li, Dongfeng
Kim, Seong-Tae
Zhang, Shijun
Zhang, Hongxing
Zheng, S. Lilly
Gui, Lixuan
Wang, Youjie
Wei, Sheng
Wang, Feng
Fang, Weimin
Liang, Yuan
Zhai, Yun
Chen, Weihong
Miao, Xiaoping
Zhou, Gangqiao
Hu, Frank B.
Lin, Dongxin
Mo, Zengnan
Wu, Tangchun
TI A genome wide association study of genetic loci that influence tumour
biomarkers cancer antigen 19-9, carcinoembryonic antigen and a
fetoprotein and their associations with cancer risk
SO GUT
LA English
DT Article
DE Cancer Genetics; Cancer Susceptibility
ID ABO BLOOD-GROUP; COLORECTAL-CANCER; PANCREATIC-CANCER;
ALPHA-FETOPROTEIN; HELICOBACTER-PYLORI; HEPATOCELLULAR-CARCINOMA;
GASTROINTESTINAL CANCER; SUSCEPTIBILITY LOCI; FOLLOW-UP; CA19-9
AB Objective Tumour biomarkers are used as indicators for cancer screening and as predictors for therapeutic responses and prognoses in cancer patients. We aimed to identify genetic loci that influence concentrations of cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and fetoprotein (AFP), and investigated the associations between the significant single nucleotide polymorphisms (SNPs) with risks of oesophageal squamous cell (OSCC), pancreatic and hepatocellular cancers.
Design We carried out a genome wide association study on plasma CA19-9, CEA and AFP concentrations in 3451 healthy Han Chinese and validated the results in 10326 individuals. Significant SNPs were further investigated in three case control studies (2031 OSCC cases and 2044 controls; 981 pancreatic cancer cases and 1991 controls; and 348 hepatocellular cancer cases and 359 controls).
Results The analyses showed association peaks on three genetic loci for CA19-9 (FUT6-FUT3 at 19p13.3, FUT2-CA11 at 19q13.3 and B3GNT3 at 19p13.1; p=1.16x10(-13)-3.30x10(-290)); four for CEA (ABO at 9q34.2, FUT6 at 19p13.3, FUT2 at 19q13.3 and FAM3B at 21q22.3; p=3.33x10(-22)-5.81x10(-209)); and two for AFP (AFP at 4q11-q13 and HISPPD2A at 15q15.3; p=3.27x10(-18) and 1.28x10(-14)). These explained 17.14% of the variations in CA19-9, 8.95% in CEA and 0.57% in AFP concentrations. Significant ABO variants were also associated with risk of OSCC and pancreatic cancers, and AFP variants with risk of hepatocellular cancer (p<0.05).
Conclusions This study identified several loci associated with CA19-9, CEA and AFP concentrations. The ABO variants were associated with risk of OSCC and pancreatic cancers and AFP variants with risk of hepatocellular cancer.
C1 [He, Meian; Guo, Huan; Zhou, Li; He, Yunfeng; Yuan, Jing; Deng, Qifei; Dai, Xiayun; Feng, Yingying; Gui, Lixuan; Wang, Youjie; Wei, Sheng; Wang, Feng; Fang, Weimin; Liang, Yuan; Chen, Weihong; Miao, Xiaoping; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Tongji Med Coll, MOE Key Lab Environm & Hlth, Wuhan 430030, Hubei, Peoples R China.
[He, Meian; Xu, Jianfeng; Gao, Yong; Tan, Aihua; Zhang, Shijun; Mo, Zengnan] Guangxi Med Univ, Inst Urol & Nephrol, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China.
[He, Meian; Xu, Jianfeng; Gao, Yong; Tan, Aihua; Zhang, Shijun; Mo, Zengnan] Guangxi Med Univ, Ctr Genom & Personalised Med, Nanning, Guangxi, Peoples R China.
[Wu, Chen; Yu, Dianke; Zhai, Kan; Chang, Jiang; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Wu, Chen; Yu, Dianke; Zhai, Kan; Chang, Jiang; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Xu, Jianfeng] Fudan Univ, Inst Urol, Huashan Hosp, Shanghai 200433, Peoples R China.
[Xu, Jianfeng; Gao, Yong] Fudan Univ, Sch Life Sci, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China.
[Xu, Jianfeng] Van Andel Res Inst, Ctr Genet Epidemiol, Grand Rapids, MI USA.
[Yang, Handong; Min, Xinwen; Zhu, Jiang; Lang, Mingjian; Li, Yi; Li, Dongfeng] Dongfeng Motor Corp, Dongfeng Cent Hosp, Dept Cardiol, Shiyan, Hubei, Peoples R China.
[Yang, Handong; Min, Xinwen; Zhu, Jiang; Lang, Mingjian; Li, Yi; Li, Dongfeng] Hubei Univ Med, Shiyan, Hubei, Peoples R China.
[Zhang, Xiaomin; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA.
[Sun, Jielin; Feng, Junjie; Kim, Seong-Tae; Zheng, S. Lilly] Wake Forest Univ, Sch Med, Ctr Canc Genom, Winston Salem, NC 27109 USA.
[Peng, Tao] Guangxi Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Nanning, Guangxi, Peoples R China.
[Peng, Tao] NCI, Lab Genom Div, NIH, Frederick, MD 21701 USA.
[Zhang, Haiying; Yang, Xiaobo] Guangxi Med Univ, Sch Publ Hlth, Dept Occupat Hlth & Environm Hlth, Nanning, Guangxi, Peoples R China.
[Qin, Xue] Guangxi Med Univ, Dept Clin Lab, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China.
[Hu, Yanling; Tao, Sha] Guangxi Med Univ, Med Sci Res Ctr, Nanning, Guangxi, Peoples R China.
[Li, Yuanfeng; Zhang, Hongxing; Zhai, Yun; Zhou, Gangqiao] Beijing Proteome Res Ctr, Beijing Inst Radiat Med, State Key Lab Prote, Beijing, Peoples R China.
RP Wu, TC (reprint author), Huazhong Univ Sci & Technol, Sch Publ Hlth, 13 Hangkong Rd, Wuhan 430030, Hubei, Peoples R China.
EM wut@mails.tjmu.edu.cn
RI miao, xiaoping/C-4336-2011; Yang, Xiaobo/G-3854-2016; Kim,
Seong-Tae/E-4474-2017
OI miao, xiaoping/0000-0002-6818-9722; Kim, Seong-Tae/0000-0001-7436-1405
FU National Basic Research Program [2011CB503800]; Programme of Introducing
Talents of Discipline to Universities; General Program of the National
Natural Science Foundation of China [30945204, 30360124, 30260110,
81222038, 81172751]; Guangxi Provincial Department of Finance and
Education [2009GJCJ150]; Fudan-VARI Centre for Genetic Epidemiology;
Fudan University Institute of Urology; Program for New Century Excellent
Talents in University
FX This work was supported by grants from the National Basic Research
Program grant (2011CB503800) and the Programme of Introducing Talents of
Discipline to Universities to TW; the General Program of the National
Natural Science Foundation of China (30945204, 30360124, 30260110,
81222038); the Guangxi Provincial Department of Finance and Education
(2009GJCJ150); intramural funding from the Fudan-VARI Centre for Genetic
Epidemiology and Fudan University Institute of Urology to ZM; and
Program for New Century Excellent Talents in University and the General
Program of the National Natural Science Foundation of China (81172751)
to MH. The funders had no role in the study design, data collection,
data analysis or interpretation of the data.
NR 52
TC 18
Z9 18
U1 3
U2 26
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JAN
PY 2014
VL 63
IS 1
BP 143
EP 151
DI 10.1136/gutjnl-2012-303434
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 263VB
UT WOS:000327835000017
PM 23300138
ER
PT J
AU Wu, C
Kraft, P
Stolzenberg-Solomon, R
Steplowski, E
Brotzman, M
Xu, MS
Mudgal, P
Amundadottir, L
Arslan, AA
Bueno-de-Mesquita, HB
Gross, M
Helzlsouer, K
Jacobs, EJ
Kooperberg, C
Petersen, GM
Zheng, W
Albanes, D
Boutron-Ruault, MC
Buring, JE
Canzian, F
Cao, GW
Duell, EJ
Elena, JW
Gaziano, JM
Giovannucci, EL
Hallmans, G
Hutchinson, A
Hunter, DJ
Jenab, M
Jiang, GL
Khaw, KT
LaCroix, A
Li, ZS
Mendelsohn, JB
Panico, S
Patel, AV
Qian, ZR
Riboli, E
Sesso, H
Shen, HB
Shu, XO
Tjonneland, A
Tobias, GS
Trichopoulos, D
Virtamo, J
Visvanathan, K
Wactawski-Wende, J
Wang, CF
Yu, K
Zeleniuch-Jacquotte, A
Chanock, S
Hoover, R
Hartge, P
Fuchs, CS
Lin, DX
Wolpin, BM
AF Wu, Chen
Kraft, Peter
Stolzenberg-Solomon, Rachael
Steplowski, Emily
Brotzman, Michelle
Xu, Mousheng
Mudgal, Poorva
Amundadottir, Laufey
Arslan, Alan A.
Bueno-de-Mesquita, H. Bas
Gross, Myron
Helzlsouer, Kathy
Jacobs, Eric J.
Kooperberg, Charles
Petersen, Gloria M.
Zheng, Wei
Albanes, Demetrius
Boutron-Ruault, Marie-Christine
Buring, Julie E.
Canzian, Federico
Cao, Guangwen
Duell, Eric J.
Elena, Joanne W.
Gaziano, J. Michael
Giovannucci, Edward L.
Hallmans, Goran
Hutchinson, Amy
Hunter, David J.
Jenab, Mazda
Jiang, Guoliang
Khaw, Kay-Tee
LaCroix, Andrea
Li, Zhaoshen
Mendelsohn, Julie B.
Panico, Salvatore
Patel, Alpa V.
Qian, Zhi Rong
Riboli, Elio
Sesso, Howard
Shen, Hongbing
Shu, Xiao-Ou
Tjonneland, Anne
Tobias, Geoffrey S.
Trichopoulos, Dimitrios
Virtamo, Jarmo
Visvanathan, Kala
Wactawski-Wende, Jean
Wang, Chengfeng
Yu, Kai
Zeleniuch-Jacquotte, Anne
Chanock, Stephen
Hoover, Robert
Hartge, Patricia
Fuchs, Charles S.
Lin, Dongxin
Wolpin, Brian M.
TI Genome-wide association study of survival in patients with pancreatic
adenocarcinoma
SO GUT
LA English
DT Article
DE Cancer Genetics; Molecular Epidemiology; Pancreatic Cancer
ID MYOTUBULARIN-RELATED PROTEIN-2; LUNG-CANCER PATIENTS; DUCTAL
ADENOCARCINOMA; GENE POLYMORPHISMS; RISK; SBF2; MICE; SUSCEPTIBILITY;
CHEMOTHERAPY; GEMCITABINE
AB Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma.
Methods We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC).
Results In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis.
Conclusions Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.
C1 [Wu, Chen; Kraft, Peter; Xu, Mousheng; Mudgal, Poorva; Giovannucci, Edward L.; Hunter, David J.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wu, Chen; Lin, Dongxin] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China.
[Wu, Chen; Wang, Chengfeng; Lin, Dongxin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Stolzenberg-Solomon, Rachael; Amundadottir, Laufey; Albanes, Demetrius; Mendelsohn, Julie B.; Tobias, Geoffrey S.; Yu, Kai; Chanock, Stephen; Hoover, Robert; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA.
[Brotzman, Michelle] Westat Corp, Rockville, MD USA.
[Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA.
[Helzlsouer, Kathy] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Helzlsouer, Kathy] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA.
[Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Program Biostat & Biomath, Seattle, WA 98104 USA.
[Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37235 USA.
[Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France.
[Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France.
[Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie E.; Gaziano, J. Michael; Sesso, Howard] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
[Canzian, Federico] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Cao, Guangwen] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China.
[Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain.
[Elena, Joanne W.] NCI, Div Canc Control & Populat Sci, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward L.; Fuchs, Charles S.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Giovannucci, Edward L.; Fuchs, Charles S.; Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Hutchinson, Amy] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France.
[Jiang, Guoliang] Fudan Univ, Canc Hosp, Dept Radiat Oncol, Shanghai 200433, Peoples R China.
[Khaw, Kay-Tee] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Clin Gerontol Unit, Cambridge CB2 2QQ, England.
[LaCroix, Andrea] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Li, Zhaoshen] Second Mil Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Shanghai, Peoples R China.
[Panico, Salvatore] Univ Naples Federico II, Dept Clin & Expt Med, Naples, Italy.
[Qian, Zhi Rong; Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Shen, Hongbing] Nanjing Med Univ, Ctr Canc, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China.
[Tjonneland, Anne] Danish Canc Soc Res Ctr, Copenhagen, Denmark.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Visvanathan, Kala] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Wang, Chengfeng] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Abdominal Surg, Beijing 100021, Peoples R China.
RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM lindx72@cicams.ac.cn; bwolpin@partners.org
RI Albanes, Demetrius/B-9749-2015; Boutron-Ruault,
Marie-Christine/H-3936-2014; Panico, Salvatore/K-6506-2016;
Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016;
OI Qian, Zhi rong/0000-0003-1633-4120; Panico,
Salvatore/0000-0002-5498-8312; Amundadottir, Laufey/0000-0003-1859-8971;
Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Tobias,
Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163
FU NCI [R01CA034588, R01CA098661, P30CA016087]; National Institute of
Environmental Health Sciences [ES000260]; National Heart, Lung, and
Blood Institute, National Institutes of Health; US Department of Health
and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221];
National Institutes of Health (Bethesda, MD) [CA 97193, CA 34944, CA
40360, HL 26490, HL 34595]; National Cancer Institute, National
Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01
CA124908]; American Society of Clinical Oncology Career Development
Award; Howard Hughes Medical Institute Early Career Physician-Scientist
Award; Lustgarten Foundation for Pancreatic Cancer Research; hanghai
Men's Health Study was supported by the National Cancer Institute
extramural research grant [R01 CA82729]; National Cancer Institute
extramural research grant [R37 CA70867]; US Public Health Service
[N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C];
Intramural Research Program of the National Cancer Institute; National
Institute of Aging [5U01AG018033]; National Cancer Institute [CA105069,
CA73790]; Associazione Italiana per la Ricerca sul Cancro
FX The NYU Women's Health Study is supported by research grants
R01CA034588, R01CA098661, center grant P30CA016087 from the NCI and
center grant ES000260 from the National Institute of Environmental
Health Sciences. The WHI programme is funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, US Department
of Health and Human Services through contracts N01WH22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221. PHS was supported by grants CA 97193, CA
34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of
Health (Bethesda, MD). The NHS, HPFS and WHS at Harvard were supported
by the National Cancer Institute, National Institutes of Health (grants
P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908). BMW was supported
by NCI K07 CA140790, an American Society of Clinical Oncology Career
Development Award, Howard Hughes Medical Institute Early Career
Physician-Scientist Award, and the Lustgarten Foundation for Pancreatic
Cancer Research. The Shanghai Men's Health Study was supported by the
National Cancer Institute extramural research grant (R01 CA82729). The
Shanghai Women's Health Study was supported by the National Cancer
Institute extramural research grant (R37 CA70867) and, partially for
biological sample collection, by the Intramural Research Program of
National Cancer Institute (Division of Cancer Epidemiology and
Genetics). PLCO was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and by contracts from the
Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The
ATBC Study was supported by US Public Health Service contracts
N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C from the
National Cancer Institute, Department of Health and Human Services, and
by funding from the Intramural Research Program of the National Cancer
Institute. The coordination of EPIC is financially supported by the
European Commission (DG- SANCO) and the International Agency for
Research on Cancer. The national cohorts are supported by Danish Cancer
Society (Denmark); Ligue contre le Cancer, Societe 3M, Mutuelle Generale
de l'Education Nationale, Institut National de la Sante et de la
Recherche Medicale (France); Deutsche Krebshilfe, Deutsches
Krebsforschungszentrum and Federal Ministry of Education and Research
(Germany); Ministry of Health and Social Solidarity, Stavros Niarchos
Foundation and Hellenic Health Foundation (Greece); Italian Association
for Research on Cancer (AIRC) and National Research Council (Italy);
Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands
Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch
ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF),
Statistics Netherlands (The Netherlands); Health Research Fund (FIS),
Regional Governments of Andalucia, Asturias, Basque Country, Murcia and
Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society,
Swedish Scientific Council and Regional Government of Skane and
Vesterbotten (Sweden); Cancer Research UK, Medical Research Council
(UK). CLUE II was supported by National Institute of Aging grant
(5U01AG018033) and National Cancer Institute grants (CA105069, CA73790).
We acknowledge the State of Maryland, the Maryland Cigarette Restitution
Fund, and the National Program of Cancer Registries (NPCR) of the
Centers for Disease Control and Prevention (CDC) for the funds that
helped support the availability of the cancer registry data.; The Cancer
Prevention Study II Nutrition Cohort is supported by the American Cancer
Society. This project has been funded in whole or in part with federal
funds from the National Cancer Institute, National Institutes of Health,
under Contract No. 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 organisations imply endorsement by the US Government.
NR 44
TC 17
Z9 18
U1 2
U2 21
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JAN
PY 2014
VL 63
IS 1
BP 152
EP 160
DI 10.1136/gutjnl-2012-303477
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 263VB
UT WOS:000327835000018
PM 23180869
ER
PT J
AU Rotman, Y
Noureddin, M
Feld, JJ
Guedj, J
Witthaus, M
Han, H
Park, YJ
Park, SH
Heller, T
Ghany, MG
Doo, E
Koh, C
Abdalla, A
Gara, N
Sarkar, S
Thomas, E
Ahlenstiel, G
Edlich, B
Titerence, R
Hogdal, L
Rehermann, B
Dahari, H
Perelson, AS
Hoofnagle, JH
Liang, TJ
AF Rotman, Yaron
Noureddin, Mazen
Feld, Jordan J.
Guedj, Jeremie
Witthaus, Michael
Han, Hwalih
Park, Yoon J.
Park, Su-Hyung
Heller, Theo
Ghany, Marc G.
Doo, Edward
Koh, Christopher
Abdalla, Adil
Gara, Naveen
Sarkar, Souvik
Thomas, Emmanuel
Ahlenstiel, Golo
Edlich, Birgit
Titerence, Rachel
Hogdal, Leah
Rehermann, Barbara
Dahari, Harel
Perelson, Alan S.
Hoofnagle, Jay H.
Liang, T. Jake
TI Effect of ribavirin on viral kinetics and liver gene expression in
chronic hepatitis C
SO GUT
LA English
DT Article
DE Hepatitis C; Interferon-Alpha
ID PEGYLATED INTERFERON; COMBINATION THERAPY; VIRUS-INFECTION; PLUS
RIBAVIRIN; ALPHA; NONRESPONDERS; PEGINTERFERON; RESPONDERS; INDUCTION;
MECHANISM
AB Objective Ribavirin improves treatment response to pegylated-interferon (PEG-IFN) in chronic hepatitis C but the mechanism remains controversial. We studied correlates of response and mechanism of action of ribavirin in treatment of hepatitis C.
Design 70 treatment-naive patients were randomised to 4weeks of ribavirin (1000-1200mg/d) or none, followed by PEG-IFN-2a and ribavirin at standard doses and durations. Patients were also randomised to a liver biopsy 24h before or 6h after starting PEG-IFN. Hepatic gene expression was assessed by microarray and interferon-stimulated gene (ISG) expression quantified by nCounter platform. Temporal changes in ISG expression were assessed by qPCR in peripheral-blood mononuclear cells (PBMC) and by serum levels of IP-10.
Results After 4weeks of ribavirin monotherapy, hepatitis C virus (HCV) levels decreased by 0.50.5 log(10) (p=0.009 vs controls) and ALT by 33% (p<0.001). Ribavirin pretreatment, while modestly augmenting ISG induction by PEG-IFN, did not modify the virological response to subsequent PEG-IFN and ribavirin treatment. However, biochemical, but not virological, response to ribavirin monotherapy predicted response to subsequent combination treatment (rapid virological response, 71% in biochemical responders vs 22% non-responders, p=0.01; early virological response, 100% vs 68%, p=0.03; sustained virological response 83% vs 41%, p=0.053). Ribavirin monotherapy lowered serum IP-10 levels but had no effect on ISG expression in PBMC.
Conclusions Ribavirin is a weak antiviral but its clinical effect seems to be mediated by a separate, indirect mechanism, which may act to reset IFN-responsiveness in HCV-infected liver.
C1 [Rotman, Yaron; Noureddin, Mazen; Feld, Jordan J.; Witthaus, Michael; Han, Hwalih; Park, Yoon J.; Park, Su-Hyung; Heller, Theo; Ghany, Marc G.; Koh, Christopher; Abdalla, Adil; Gara, Naveen; Sarkar, Souvik; Thomas, Emmanuel; Ahlenstiel, Golo; Edlich, Birgit; Titerence, Rachel; Hogdal, Leah; Rehermann, Barbara; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Guedj, Jeremie; Dahari, Harel; Perelson, Alan S.] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA.
[Guedj, Jeremie] INSERM, UMR 738, F-75018 Paris, France.
[Guedj, Jeremie] Univ Paris Diderot, Sorbonne Paris Cite, UMR 738, F-75018 Paris, France.
[Doo, Edward] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Dahari, Harel] Univ Illinois, Dept Med, Chicago, IL USA.
[Dahari, Harel] Loyola Univ Chicago, Dept Med, Div Hepatol, Maywood, IL USA.
RP Rotman, Y (reprint author), NIDDK, NIH, Liver Dis Branch, 10 Ctr Dr,Bldg 10,Room 9C434,MSC1800, Bethesda, MD 20892 USA.
EM rotmany@mail.nih.gov
RI Park, Su-Hyung/N-3514-2014; Guedj, Jeremie/A-6842-2017;
OI Guedj, Jeremie/0000-0002-5534-5482; Rotman, Yaron/0000-0002-7549-8216;
Sarkar, Souvik/0000-0002-9358-4257; Ahlenstiel, Golo/0000-0003-0026-1457
FU NIDDK; NIH [R01-OD011095, R37-AI028433, R01-AI078881, R34-HL109334,
P20-GM103452]; University of Illinois Walter Payton Liver Center GUILD
FX The study was supported by the intramural research program of NIDDK; NIH
grants R01-OD011095, R37-AI028433, R01-AI078881, R34-HL109334 and
P20-GM103452; and the University of Illinois Walter Payton Liver Center
GUILD.
NR 27
TC 24
Z9 25
U1 1
U2 14
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JAN
PY 2014
VL 63
IS 1
BP 161
EP 169
DI 10.1136/gutjnl-2012-303852
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 263VB
UT WOS:000327835000019
PM 23396509
ER
PT J
AU Attygalle, AD
Cabecadas, J
Gaulard, P
Jaffe, ES
de Jong, D
Ko, YH
Said, J
Klapper, W
AF Attygalle, Ayoma D.
Cabecadas, Jose
Gaulard, Philippe
Jaffe, Elaine S.
de Jong, Daphne
Ko, Young Hyeh
Said, Jonathan
Klapper, Wolfram
TI Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step
forward - report on the lymphoma workshop of the XVIth meeting of the
European Association for Haematopathology and the Society for
Hematopathology
SO HISTOPATHOLOGY
LA English
DT Article
DE angioimmunoblastic; CD30; Epstein-Barr virus; follicular T-helper;
T-cell lymphoma
ID CLASSICAL HODGKIN LYMPHOMA; BARR-VIRUS INFECTION; HYPERPLASTIC
GERMINAL-CENTERS; GRANULAR LYMPHOCYTIC-LEUKEMIA; REFRACTORY
CELIAC-DISEASE; LYMPHOPROLIFERATIVE DISORDERS; PROGNOSTIC-FACTORS;
CLINICOPATHOLOGICAL CHARACTERISTICS; FOXP3 EXPRESSION; GROWTH-PATTERN
AB Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among the broad category of non-Hodgkin lymphomas. Owing to the lack of specific genetic alterations in the vast majority, most currently defined entities show overlapping morphological and immunophenotypic features, and therefore pose a challenge to the diagnostic pathologist. In the light of recent immunophenotypic, cytogenetic and molecular genetics advances in the field of T-cell and T/NK-cell lymphomas, the focus of the lymphoma workshop of the European Association for Haematopathology/Society for Hematopathology meeting in Lisbon, Portugal, in October 2012 was to refine existing diagnostic criteria and clarify the borders between overlapping entities. The panel reviewed over 200 submitted cases, which were grouped into five categories: (i) angioimmunoblastic T-cell lymphoma and T-follicular-helper-cell-associated lymphomas; (ii) CD30-positive T-cell lymphomas/lymphoproliferative diseases; (iii) extranodal T-cell and NK-cell neoplasms; (iv) EBV-associated T-cell/NK-cell lymphomas/lymphoproliferative diseases; and (v) peripheral T-cell lymphoma, not otherwise specified, post-transplant lymphoproliferative disorders, and mimics. This report summarizes the discussions and conclusions of the workshop, which question current diagnostic criteria and provide recommendations for refining existing classifications.
C1 [Attygalle, Ayoma D.] Royal Marsden Hosp, Dept Histopathol, London SW3 6JJ, England.
[Cabecadas, Jose] IPOLFG, Serv Anat Patol, Lisbon, Portugal.
[Gaulard, Philippe] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Dept Pathol, Creteil, France.
[Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[de Jong, Daphne] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Ko, Young Hyeh] Sungkyunkwan Univ, Samsung Med Ctr, Dept Pathol, Seoul, South Korea.
[Said, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA.
[Klapper, Wolfram] Univ Kiel, Dept Pathol, Haematopathol Sect, Kiel, Germany.
[Klapper, Wolfram] Univ Kiel, Lymph Node Registry, Kiel, Germany.
RP Attygalle, AD (reprint author), Royal Marsden Hosp, Dept Histopathol, Fulham Rd, London SW3 6JJ, England.
EM Ayoma.Attygalle@rmh.nhs.uk; wklapper@path.uni-kiel.de
RI Klapper, Wolfram/S-6314-2016;
OI Jaffe, Elaine/0000-0003-4632-0301; Cabecadas, Jose/0000-0001-6232-1596
NR 92
TC 29
Z9 31
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0309-0167
EI 1365-2559
J9 HISTOPATHOLOGY
JI Histopathology
PD JAN
PY 2014
VL 64
IS 2
BP 171
EP 199
DI 10.1111/his.12251
PG 29
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 270VR
UT WOS:000328347800001
PM 24128129
ER
PT J
AU Crooks, DR
Natarajan, TG
Jeong, SY
Chen, CM
Park, SY
Huang, HZ
Ghosh, MC
Tong, WH
Haller, RG
Wu, C
Rouault, TA
AF Crooks, Daniel R.
Natarajan, Thanemozhi G.
Jeong, Suh Young
Chen, Chuming
Park, Sun Young
Huang, Hongzhan
Ghosh, Manik C.
Tong, Wing-Hang
Haller, Ronald G.
Wu, Cathy
Rouault, Tracey A.
TI Elevated FGF21 secretion, PGC-1 alpha and ketogenic enzyme expression
are hallmarks of iron-sulfur cluster depletion in human skeletal muscle
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ACTIVATED RECEPTOR-ALPHA; FATTY-ACID OXIDATION; MYOSIN HEAVY-CHAIN;
MITOCHONDRIAL MYOPATHY; SUCCINATE-DEHYDROGENASE; PAROXYSMAL
MYOGLOBINURIA; BIOINFORMATICS RESOURCES; ACONITASE DEFICIENCY;
HEREDITARY MYOPATHY; FRIEDREICH ATAXIA
AB Iron-sulfur (Fe-S) clusters are ancient enzyme cofactors found in virtually all life forms. We evaluated the physiological effects of chronic Fe-S cluster deficiency in human skeletal muscle, a tissue that relies heavily on Fe-S cluster-mediated aerobic energy metabolism. Despite greatly decreased oxidative capacity, muscle tissue from patients deficient in the Fe-S cluster scaffold protein ISCU showed a predominance of type I oxidative muscle fibers and higher capillary density, enhanced expression of transcriptional co-activator PGC-1 alpha and increased mitochondrial fatty acid oxidation genes. These Fe-S cluster-deficient muscles showed a dramatic up-regulation of the ketogenic enzyme HMGCS2 and the secreted protein FGF21 (fibroblast growth factor 21). Enhanced muscle FGF21 expression was reflected by elevated circulating FGF21 levels in the patients, and robust FGF21 secretion could be recapitulated by respiratory chain inhibition in cultured myotubes. Our findings reveal that mitochondrial energy starvation elicits a coordinated response in Fe-S-deficient skeletal muscle that is reflected systemically by increased plasma FGF21 levels.
C1 [Crooks, Daniel R.; Natarajan, Thanemozhi G.; Wu, Cathy] Georgetown Univ, Med Ctr, Dept Biochem Mol & Cellular Biol, Washington, DC 20057 USA.
[Crooks, Daniel R.; Jeong, Suh Young; Ghosh, Manik C.; Tong, Wing-Hang; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
[Chen, Chuming; Huang, Hongzhan; Wu, Cathy] Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19711 USA.
[Park, Sun Young; Haller, Ronald G.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75231 USA.
[Park, Sun Young; Haller, Ronald G.] VA North Texas Med Ctr, Dallas, TX 75231 USA.
[Park, Sun Young; Haller, Ronald G.] Inst Exercise & Environm Med, Neuromuscular Ctr, Dallas, TX 75231 USA.
RP Rouault, TA (reprint author), NICHHD, Program Mol Med, Bldg 18T,Room 101,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rouault@helix.nih.gov
OI Jeong, Suh Young/0000-0002-6376-7001
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; NIAMS [R01 AR050597]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, and NIAMS grant #R01 AR050597.
NR 70
TC 20
Z9 20
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JAN 1
PY 2014
VL 23
IS 1
BP 24
EP 39
DI 10.1093/hmg/ddt393
PG 16
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 272SZ
UT WOS:000328482300003
PM 23943793
ER
PT J
AU McCoy, MK
Kaganovich, A
Rudenko, IN
Ding, JH
Cookson, MR
AF McCoy, Melissa K.
Kaganovich, Alice
Rudenko, Iakov N.
Ding, Jinhui
Cookson, Mark R.
TI Hexokinase activity is required for recruitment of parkin to depolarized
mitochondria
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DEPENDENT ANION CHANNEL; PINK1/PARKIN-MEDIATED MITOPHAGY; DAMAGED
MITOCHONDRIA; UBIQUITIN LIGASE; CELL-DEATH; PINK1; LOCALIZATION;
ACTIVATION; PHOSPHORYLATION; TRANSLOCATION
AB Autosomal recessive parkinsonism genes contribute to maintenance of mitochondrial function. Two of these, PINK1 and parkin, act in a pathway promoting autophagic removal of depolarized mitochondria. Although recruitment of parkin to mitochondria is PINK1-dependent, additional components necessary for signaling are unclear. We performed a screen for endogenous modifiers of parkin recruitment to depolarized mitochondria and identified hexokinase 2 (HK2) as a novel modifier of depolarization-induced parkin recruitment. Hexose kinase activity was required for parkin relocalization, suggesting the effects are shared among hexokinases including the brain-expressed hexokinase 1 (HK1). Knockdown of both HK1 and HK2 led to a stronger block in parkin relocalization than either isoform alone, and expression of HK2 in primary neurons promoted YFP-parkin recruitment to depolarized mitochondria. Mitochondrial parkin recruitment was attenuated with AKT inhibition, which is known to modulate HK2 activity and mitochondrial localization. We, therefore, propose that Akt-dependent recruitment of hexokinases is a required step in the recruitment of parkin prior to mitophagy.
C1 [McCoy, Melissa K.; Kaganovich, Alice; Rudenko, Iakov N.; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Ding, Jinhui] NIA, Computat Biol Core, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU National Institutes of Health, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging.
NR 47
TC 23
Z9 23
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JAN 1
PY 2014
VL 23
IS 1
BP 145
EP 156
DI 10.1093/hmg/ddt407
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 272SZ
UT WOS:000328482300012
PM 23962723
ER
PT J
AU Hinrichs, CS
Rosenberg, SA
AF Hinrichs, Christian S.
Rosenberg, Steven A.
TI Exploiting the curative potential of adoptive T-cell therapy for cancer
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE immunotherapies; gene therapy; T cells; cancer; antigens; tumor immunity
ID TUMOR-INFILTRATING LYMPHOCYTES; EPSTEIN-BARR-VIRUS; METASTATIC MELANOMA
PATIENTS; COLONY-STIMULATING FACTOR; FACTOR RECEPTOR EGFRVIII; HIGH-DOSE
INTERLEUKIN-2; CARBONIC-ANHYDRASE-IX; LYMPHOPROLIFERATIVE DISEASE;
CERVICAL-CANCER; STEM-CELLS
AB Adoptive T-cell therapy (ACT) is a potent and flexible cancer treatment modality that can induce complete, durable regression of certain human malignancies. Long-term follow-up of patients receiving tumor-infiltrating lymphocytes (TILs) for metastatic melanoma reveals a substantial subset that experienced complete, lasting tumor regression - and may be cured. Increasing evidence points to mutated gene products as the primary immunological targets of TILs from melanomas. Recent technological advances permit rapid identification of the neoepitopes resulting from these somatic gene mutations and of T cells with reactivity against these targets. Isolation and adoptive transfer of these T cells may improve TIL therapy for melanoma and permit its broader application to non-melanoma tumors. Extension of ACT to other malignancies may also be possible through antigen receptor gene engineering. Tumor regression has been observed following transfer of T cells engineered to express chimeric antigen receptors against CD19 in B-cell malignancies or a T-cell receptor against NY-ESO-1 in synovial cell sarcoma and melanoma. Herein, we review recent clinical trials of TILs and antigen receptor gene therapy for advanced cancers. We discuss lessons from this experience and consider how they might be applied to realize the full curative potential of ACT.
C1 [Hinrichs, Christian S.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
RP Hinrichs, CS (reprint author), NCI, Surg Branch, 10 Ctr Dr,CRC Room 3-3888, Bethesda, MD 20892 USA.
EM hinrichs@nih.gov
FU NIH intramural research program
FX The research is funded by the NIH intramural research program. The
authors have no conflicts of interest to declare.
NR 135
TC 115
Z9 121
U1 3
U2 64
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD JAN
PY 2014
VL 257
IS 1
SI SI
BP 56
EP 71
DI 10.1111/imr.12132
PG 16
WC Immunology
SC Immunology
GA 272JB
UT WOS:000328455300004
PM 24329789
ER
PT J
AU Fowler, DH
AF Fowler, Daniel H.
TI Rapamycin-resistant effector T-cell therapy
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE Th1; Th2; Th17; graft versus host disease; apoptosis; autophagy;
transplantation; cytokines
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TUMOR-SUPPRESSOR
COMPLEX; ANTIGEN-PRESENTING CELLS; DONOR TH2 CELLS; GRAFT-REJECTION;
IN-VIVO; MAMMALIAN TARGET; CYCLE PROGRESSION; KINASE INHIBITOR
AB Pharmacologic inhibition of the mechanistic target of rapamycin (mTOR) represents a stress test for tumor cells and T cells. Mechanisms exist that allow cells to survive this stress, including suboptimal target block, alternative signaling pathways, and autophagy. Rapamycin-resistant effector T (T-Rapa) cells have an altered phenotype that associates with increased function. Ex vivo rapamycin, when used in combination with polarizing cytokines and antigen-presenting-cell free costimulation, is a flexible therapeutic approach as polarization to T-helper 1 (Th1)- or Th2-type effectors is possible. Murine T-Rapa cells skewed toward a Th2-type prevented graft rejection and graft-versus-host disease (GVHD) more potently than control Th2 cells and effectively balanced GVHD and graft-versus-tumor (GVT) effects. A phase II clinical trial using low-intensity allogeneic hematopoietic cell transplantation demonstrated that interleukin-4 polarized human T-Rapa cells had a mixed Th2/Th1 phenotype; T-Rapa cell recipients had a balanced Th2/Th1 cytokine profile, conversion of mixed chimerism toward full donor chimerism, and a potentially favorable balance between GVHD and GVT effects. In addition, a phase I clinical trial evaluating autologous T-Rapa cells skewed toward a Th1- and Tc1-type is underway. Use of ex vivo rapamycin to modulate effector T-cell function represents a promising new approach to transplantation therapy.
C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Fowler, DH (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, 10 Ctr Dr,CRC,3-EAST Labs,3-3330, Bethesda, MD 20892 USA.
EM dhfowler@helix.nih.gov
NR 147
TC 4
Z9 4
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD JAN
PY 2014
VL 257
IS 1
SI SI
BP 210
EP 225
DI 10.1111/imr.12127
PG 16
WC Immunology
SC Immunology
GA 272JB
UT WOS:000328455300014
PM 24329799
ER
PT J
AU Crompton, JG
Sukumar, M
Restifo, NP
AF Crompton, Joseph G.
Sukumar, Madhusudhanan
Restifo, Nicholas P.
TI Uncoupling T-cell expansion from effector differentiation in cell-based
immunotherapy
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE adoptive cell transfer; T-cell based-therapy; effector differentiation;
replicative senescence; CD8(+) T cells; adoptive cellular immunotherapy
ID PLURIPOTENT STEM-CELLS; TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC
MELANOMA PATIENTS; IN-VIVO; ADOPTIVE IMMUNOTHERAPY; TRANSFER THERAPY;
CD27-CD70 INTERACTIONS; REPROGRAMMING FACTORS; LINEAGE RELATIONSHIP;
CD27 STIMULATION
AB Adoptive cellular immunotherapy (ACT) is a potentially curative therapy for patients with advanced cancer. Eradication of tumor in mouse models and humans correlates with both a high dose of adoptively transferred cells and cells with a minimally differentiated phenotype that maintain replicative capacity and multipotency. We speculate that response to ACT not only requires transfer of cells with immediate cytolytic effector function to kill the bulk of fast-growing tumor but also transfer of tumor-specific cells that maintain an ability for self-renewal and the capacity to produce a continual supply of cytolytic effector progeny until all malignant cells are eliminated. Current in vitro methods to expand cells to sufficient numbers and still maintain a minimally differentiated phenotype are hindered by the biological coupling of clonal expansion and effector differentiation. Therefore, a better understanding of the physiologic mechanism that couples cell expansion and differentiation in CD8(+) T cells may improve the efficacy of ACT.
C1 [Crompton, Joseph G.; Sukumar, Madhusudhanan; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Crompton, Joseph G.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Crompton, Joseph G.] Univ Cambridge, Sch Clin Med, Dept Med, Cambridge, England.
RP Restifo, NP (reprint author), NCI, NIH, Mark O Hatfield Clin Res Ctr, Room 3-5672,10 Ctr Dr, Bethesda, MD 20892 USA.
EM restifo@nih.gov
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural Research Program of the NIH, National Cancer Institute;
Center for Cancer Research; Wellcome Trust Translational Medicine and
Therapeutics Programme
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, and Center for Cancer Research. J. G.
Crompton also acknowledges funding support from the Wellcome Trust
Translational Medicine and Therapeutics Programme. The authors have no
conflicting financial interests.
NR 105
TC 30
Z9 30
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD JAN
PY 2014
VL 257
IS 1
SI SI
BP 264
EP 276
DI 10.1111/imr.12135
PG 13
WC Immunology
SC Immunology
GA 272JB
UT WOS:000328455300018
PM 24329803
ER
PT J
AU Pavletic, AJ
Pao, M
Pine, DS
Luckenbaugh, DA
Rosing, DR
AF Pavletic, A. J.
Pao, M.
Pine, D. S.
Luckenbaugh, D. A.
Rosing, D. R.
TI Screening electrocardiograms in psychiatric research: implications for
physicians and healthy volunteers
SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; ECG; INTERVAL
AB AimsWhile there is controversy regarding utility of screening electrocardiograms (ECGs) in competitive athletes and children exposed to psychostimulants, there is no data on the use of screening ECGs in psychiatric research. We aimed to examine the prevalence and clinical significance of ECG abnormalities and their impact on eligibility for studies.
MethodsWe analysed 500 consecutive ECG reports from physically healthy volunteers who had a negative cardiac history, normal cardiovascular examination and no other significant medical illnesses. For the purpose of this report, all ECGs were over-read by one cardiologist.
ResultsThe mean age of our cohort was 28.38.0years. A total of 112 (22.4%) ECGs were reported as abnormal (14.2%) or borderline (8.2%). These abnormalities were considered clinically insignificant in all but eight subjects (1.6%) who underwent evaluation with an echocardiogram. All echocardiograms were normal. No subject was excluded from studies. After the over-reading, no abnormalities or isolated bradycardia were present in 37 of 112 (33%) ECGs that were initially reported as abnormal or borderline, while minor abnormalities were found in 7 of 204 (3.4%) ECGs that were reported as normal.
ConclusionsAlthough screening ECGs did not detect significant cardiac pathology or affect eligibility for our studies, over 20% of subjects were labelled as having an abnormal or borderline ECG which was incorrect in one-third of cases. Strategies to minimise unintended consequences of screening are discussed.
C1 [Pavletic, A. J.; Pao, M.] NIMH, Off Clin Director, Bethesda, MD 20982 USA.
[Pine, D. S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20982 USA.
[Luckenbaugh, D. A.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20982 USA.
[Rosing, D. R.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
RP Pavletic, AJ (reprint author), NIMH, 10 Ctr Dr,6-5340,MSC 1276, Bethesda, MD 20982 USA.
EM pavletia@mail.nih.gov
FU National Institute of Mental Health
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 24
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1368-5031
EI 1742-1241
J9 INT J CLIN PRACT
JI Int. J. Clin. Pract.
PD JAN
PY 2014
VL 68
IS 1
BP 117
EP 121
DI 10.1111/ijcp.12218
PG 5
WC Medicine, General & Internal; Pharmacology & Pharmacy
SC General & Internal Medicine; Pharmacology & Pharmacy
GA 271ET
UT WOS:000328375000015
PM 24341305
ER
PT J
AU Harnof, S
Hananel, A
Zilby, Z
Kulbatski, I
Hadani, M
Kassell, N
AF Harnof, Sagi
Hananel, Arik
Zilby, Zion
Kulbatski, Iris
Hadani, Moshe
Kassell, Neal
TI Potential of magnetic resonance-guided focused ultrasound for
intracranial hemorrhage: an in vitro feasibility study
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE intracranial hemorrhage; magnetic resonance-guided focused ultrasound;
noninvasive; stroke; thrombolysis
ID ACUTE ISCHEMIC-STROKE; INTRACEREBRAL HEMORRHAGE; BRAIN; THROMBOLYSIS;
SURGERY; ABLATION; SYSTEM; RABBIT; MODEL
AB Background Intracranial hemorrhage has a mortality rate of up to 40-60% due to the lack of effective treatment. Magnetic resonance-guided focused ultrasound may offer a breakthrough noninvasive technology, by allowing accurate delivery of focused ultrasound, under the guidance of real-time magnetic resonance imaging.
Aim The purpose of the current study was to optimize the acoustic parameters of magnetic resonance-guided focused ultrasound for effective clot liquefaction, in order to evaluate the feasibility of magnetic resonance-guided focused ultrasound for thrombolysis.
Methods Body (11MHz) and brain (220kHz) magnetic resonance-guided focused ultrasound systems (InSightec Ltd, Tirat Carmel, Israel) were used to treat tube-like (4cc), round (10cc), and bulk (300cc) porcine blood clots in vitro, using burst sonications of one-second to five-seconds, a duty cycle of 5-50%, and peak acoustic powers between 600 and 1200W. Liquefied volumes were measured as hyperintense regions on T2-weighted magnetic resonance images for body unit sonications (duration of one-second, duty cycle of 10%, and power of 500-1200W). Liquefaction efficiency was calculated for brain unit sonications (duration of one-second, duty cycle of 10%, power of 600W, and burst length between 01ms and 100ms).
Results Liquified lesion volume increased as power was raised, without a thermal rise. For brain unit sonications, a power setting of 600W and ultrashort sonications (burst length between 01 and 10ms) resulted in liquefaction efficacy above 50%, while longer burst duration yielded lower efficacy.
Conclusions These results demonstrate the feasibility of obtaining reproducible, rapid, efficient, and accurate blood clot lysis using the magnetic resonance-guided focused ultrasound system. Further in vivo studies are needed to validate the feasibility of magnetic resonance-guided focused ultrasound as a treatment modality for intracranial hemorrhage.
C1 [Harnof, Sagi; Hadani, Moshe] Chaim Sheba Med Ctr, Dept Neurosurg, IL-52621 Tel Hashomer, Israel.
[Hananel, Arik] FUS Fdn, Charlottesville, VA USA.
[Zilby, Zion] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kulbatski, Iris] Toronto Western Res Inst, Dept Genet & Dev, Toronto, ON M5T 2S8, Canada.
[Kassell, Neal] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA.
RP Harnof, S (reprint author), Chaim Sheba Med Ctr, Dept Neurosurg, IL-52621 Tel Hashomer, Israel.
EM Sagi.harnof@sheba.health.gov.il
NR 16
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD JAN
PY 2014
VL 9
IS 1
BP 40
EP 47
DI 10.1111/ijs.12051
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 275CO
UT WOS:000328653500011
PM 23803153
ER
PT J
AU Efthymiou, A
Shaltouki, A
Steiner, JP
Jha, B
Heman-Ackah, SM
Swistowski, A
Zeng, XM
Rao, MS
Malik, N
AF Efthymiou, Anastasia
Shaltouki, Atossa
Steiner, Joseph P.
Jha, Balendu
Heman-Ackah, Sabrina M.
Swistowski, Andrzej
Zeng, Xianmin
Rao, Mahendra S.
Malik, Nasir
TI Functional Screening Assays with Neurons Generated from Pluripotent Stem
Cell-Derived Neural Stem Cells
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE neurons; drug discovery; neural stem cells
ID DOPAMINERGIC-NEURONS; DEFINED CONDITIONS; DRUG DISCOVERY; EFFICIENT
GENERATION; DISEASE; LINES; IMMORTALIZATION; DYSFUNCTION; MODELS
AB Rapid and effective drug discovery for neurodegenerative disease is currently impeded by an inability to source primary neural cells for high-throughput and phenotypic screens. This limitation can be addressed through the use of pluripotent stem cells (PSCs), which can be derived from patient-specific samples and differentiated to neural cells for use in identifying novel compounds for the treatment of neurodegenerative diseases. We have developed an efficient protocol to culture pure populations of neurons, as confirmed by gene expression analysis, in the 96-well format necessary for screens. These differentiated neurons were subjected to viability assays to illustrate their potential in future high-throughput screens. We have also shown that organelles such as nuclei and mitochondria could be live-labeled and visualized through fluorescence, suggesting that we should be able to monitor subcellular phenotypic changes. Neurons derived from a green fluorescent protein-expressing reporter line of PSCs were live-imaged to assess markers of neuronal maturation such as neurite length and co-cultured with astrocytes to demonstrate further maturation. These studies confirm that PSC-derived neurons can be used effectively in viability and functional assays and pave the way for high-throughput screens on neurons derived from patients with neurodegenerative disorders.
C1 [Efthymiou, Anastasia; Jha, Balendu; Heman-Ackah, Sabrina M.; Rao, Mahendra S.; Malik, Nasir] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Shaltouki, Atossa; Zeng, Xianmin] Buck Inst Res Aging, Novato, CA USA.
[Steiner, Joseph P.] NINDS, Neurotherapeut Dev Unit, Translat Neurosci Ctr, NIH, Bethesda, MD 20892 USA.
[Swistowski, Andrzej] XCell Sci Inc, Novato, CA USA.
[Rao, Mahendra S.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Malik, N (reprint author), NIAMSD, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM malikn@mail.nih.gov
OI Jha, Balendu Shekhar/0000-0002-6509-8171; Efthymiou,
Anastasia/0000-0002-1769-5078
FU NIH Common Fund
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the NIH Common Fund.
NR 27
TC 17
Z9 17
U1 1
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JAN
PY 2014
VL 19
IS 1
SI SI
BP 32
EP 43
DI 10.1177/1087057113501869
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 272GC
UT WOS:000328447300003
PM 24019252
ER
PT J
AU Shahane, SA
Huang, RL
Gerhold, D
Baxa, U
Austin, CP
Xia, MH
AF Shahane, Sampada A.
Huang, Ruili
Gerhold, David
Baxa, Ulrich
Austin, Christopher P.
Xia, Menghang
TI Detection of Phospholipidosis Induction: A Cell-Based Assay in
High-Throughput and High-Content Format
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE LipidTOX; phospholipidosis; qHTS
ID DRUG-INDUCED PHOSPHOLIPIDOSIS; INDUCED PULMONARY TOXICITY; IN-VITRO;
AMPHIPHILIC DRUGS; LAMELLAR BODIES; AMIODARONE; NEPHROTOXICITY;
ESTABLISHMENT; HEPATOCYTES; RECEPTORS
AB Drug-induced phospholipidosis is characterized by the accumulation of intracellular phospholipids in cells exposed to cationic amphiphilic drugs. The appearance of unicentric or multicentric multilamellar bodies viewed under an electron microscope (EM) is the morphological hallmark of phospholipidosis. Although the EM method is the gold standard for detecting cellular phospholipidosis, this method has its drawbacks, including low throughput, high cost, and unsuitability for screening a large chemical library. In this study, a cell-based phospholipidosis assay has been developed using the LipidTOX Red reagent in HepG2 cells and miniaturized into a 1536-well plate format. To validate this assay for high-throughput screening (HTS), the LOPAC library of 1280 compounds was screened using a quantitative HTS platform. A group of known phospholipidosis inducers, such as amiodarone, propranolol, chlorpromazine, desipramine, promazine, clomipramine, and amitriptyline, was identified by the screen, consistent with previous reports. Several novel phospholipidosis inducers, including NAN-190, ebastine, GR127935, and cis-(Z)-flupentixol, were identified in this study and confirmed using the EM method. These results demonstrate that this assay can be used to evaluate and profile large numbers of chemicals for drug-induced phospholipidosis.
C1 [Shahane, Sampada A.; Huang, Ruili; Gerhold, David; Austin, Christopher P.; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Baxa, Ulrich] SAIC Frederick Inc, Electron Microscopy Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Xia, MH (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM mxia@mail.nih.gov
FU Intramural Research Programs of the National Toxicology Program,
National Institute of Environmental Health Sciences [Y2-ES-7020-01];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the Intramural Research Programs (Interagency agreement
Y2-ES-7020-01) of the National Toxicology Program, National Institute of
Environmental Health Sciences, and the National Cancer Institute
(Contract No. HHSN261200800001E), National Institutes of Health.
NR 34
TC 5
Z9 5
U1 0
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JAN
PY 2014
VL 19
IS 1
SI SI
BP 66
EP 76
DI 10.1177/1087057113502851
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 272GC
UT WOS:000328447300006
PM 24003057
ER
PT J
AU Xu, M
Liu, K
Swaroop, M
Sun, W
Dehdashti, SJ
McKew, JC
Zheng, W
AF Xu, Miao
Liu, Ke
Swaroop, Manju
Sun, Wei
Dehdashti, Seameen J.
McKew, John C.
Zheng, Wei
TI A Phenotypic Compound Screening Assay for Lysosomal Storage Diseases
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE Lysotracker; enlarged lysosome; lysosomal storage diseases; Niemann Pick
disease type C; cyclodextrin
ID EXOCYTOSIS; DISORDERS; NEURONS
AB The lysosome is a vital cellular organelle that primarily functions as a recycling center for breaking down unwanted macromolecules through a series of hydrolases. Functional deficiencies in lysosomal proteins due to genetic mutations have been found in more than 50 lysosomal storage diseases that exhibit characteristic lipid/macromolecule accumulation and enlarged lysosomes. Recently, the lysosome has emerged as a new therapeutic target for drug development for the treatment of lysosomal storage diseases. However, a suitable assay for compound screening against the diseased lysosomes is currently unavailable. We have developed a Lysotracker staining assay that measures the enlarged lysosomes in patient-derived cells using both fluorescence intensity readout and fluorescence microscopic measurement. This phenotypic assay has been tested in patient cells obtained from several lysosomal storage diseases and validated using a known compound, methyl--cyclodextrin, in primary fibroblast cells derived from Niemann Pick C disease patients. The results demonstrate that the Lysotracker assay can be used in compound screening for the identification of lead compounds that are capable of reducing enlarged lysosomes for drug development.
C1 [Xu, Miao; Liu, Ke; Swaroop, Manju; Sun, Wei; Dehdashti, Seameen J.; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Xu, Miao] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou 310003, Zhejiang, Peoples R China.
RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of the Therapeutics for Rare and Neglected
Diseases, National Center for Advancing Translational Sciences, National
Institutes of Health
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by the Intramural Research Program of the Therapeutics for
Rare and Neglected Diseases, National Center for Advancing Translational
Sciences, National Institutes of Health.
NR 15
TC 11
Z9 11
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JAN
PY 2014
VL 19
IS 1
SI SI
BP 168
EP 175
DI 10.1177/1087057113501197
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 272GC
UT WOS:000328447300015
PM 23983233
ER
PT J
AU Koh, DH
Bhatti, P
Coble, JB
Stewart, PA
Lu, W
Shu, XO
Ji, BT
Xue, SZ
Locke, SJ
Portengen, L
Yang, G
Chow, WH
Gao, YT
Rothman, N
Vermeulen, R
Friesen, MC
AF Koh, Dong-Hee
Bhatti, Parveen
Coble, Joseph B.
Stewart, Patricia A.
Lu, Wei
Shu, Xiao-Ou
Ji, Bu-Tian
Xue, Shouzheng
Locke, Sarah J.
Portengen, Lutzen
Yang, Gong
Chow, Wong-Ho
Gao, Yu-Tang
Rothman, Nathaniel
Vermeulen, Roel
Friesen, Melissa C.
TI Calibrating a population-based job-exposure matrix using inspection
measurements to estimate historical occupational exposure to lead for a
population-based cohort in Shanghai, China
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE lead; cancer; exposure assessment; occupational exposure; job-exposure
matrix; mixed-effects model
ID ADULT BRAIN-TUMORS; REPUBLIC-OF-CHINA; BLOOD LEAD; CANCER; RISK;
WORKERS; HEALTH; STATES; SIZE
AB The epidemiologic evidence for the carcinogenicity of lead is inconsistent and requires improved exposure assessment to estimate risk. We evaluated historical occupational lead exposure for a population-based cohort of women (n 74,942) by calibrating a job-exposure matrix (JEM) with lead fume (n = 20,084) and lead dust (n = 5383) measurements collected over four decades in Shanghai, China. Using mixed-effect models, we calibrated intensity JEM ratings to the measurements using fixed-effects terms for year and JEM rating. We developed job/industry-specific estimates from the random-effects terms for job and industry. The model estimates were applied to subjects' jobs when the JEM probability rating was high for either job or industry; remaining jobs were considered unexposed. The models predicted that exposure increased monotonically with JEM intensity rating and decreased 20-50-fold over time. The cumulative calibrated JEM estimates and job/industry-specific estimates were highly correlated (Pearson correlation = 0.79-0.84). Overall, 5% of the person-years and 8% of the women were exposed to lead fume; 2% of the person-years and 4% of the women were exposed to lead dust. The most common lead-exposed jobs were manufacturing electronic equipment. These historical lead estimates should enhance our ability to detect associations between lead exposure and cancer risk in the future epidemiologic analyses.
C1 [Koh, Dong-Hee; Coble, Joseph B.; Stewart, Patricia A.; Ji, Bu-Tian; Xue, Shouzheng; Locke, Sarah J.; Chow, Wong-Ho; Rothman, Nathaniel; Friesen, Melissa C.] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Bhatti, Parveen] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA.
[Stewart, Patricia A.] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Arlington, VA USA.
[Lu, Wei] Shanghai Municipal Ctr Dis Control, Shanghai, Peoples R China.
[Shu, Xiao-Ou; Yang, Gong] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Portengen, Lutzen; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, Utrecht, Netherlands.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Friesen, MC (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Executive Blvd,Room 8106, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Friesen, Melissa/A-5362-2009; Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU US National Institutes of Health [R37 CA70867]; Intramural Research
Program of the National Institutes of Health [N02 CP1101066]
FX This research was supported by the US National Institutes of Health
(grant R37 CA70867) and the Intramural Research Program of the National
Institutes of Health (contract N02 CP1101066).
NR 38
TC 10
Z9 10
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
EI 1559-064X
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD JAN-FEB
PY 2014
VL 24
IS 1
BP 9
EP 16
DI 10.1038/jes.2012.86
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 274KJ
UT WOS:000328604900003
PM 22910004
ER
PT J
AU Brandt, AL
Hagos, Y
Yacob, Y
David, VA
Georgiadis, NJ
Shoshani, J
Roca, AL
AF Brandt, Adam L.
Hagos, Yohannes
Yacob, Yohannes
David, Victor A.
Georgiadis, Nicholas J.
Shoshani, Jeheskel
Roca, Alfred L.
TI The Elephants of Gash-Barka, Eritrea: Nuclear and Mitochondrial Genetic
Patterns
SO JOURNAL OF HEREDITY
LA English
DT Article
DE fecal DNA; Loxodonta; microsatellites; mitochondrial DNA; single
nucleotide polymorphism; war elephants
ID TETRANUCLEOTIDE MICROSATELLITE LOCI; POPULATION-STRUCTURE; AFRICAN
ELEPHANTS; GENOMIC DISSOCIATION; DNA; PHYLOGENIES; SEQUENCES; FOREST
AB Eritrea has one of the northernmost populations of African elephants. Only about 100 elephants persist in the Gash-Barka administrative zone. Elephants in Eritrea have become completely isolated, with no gene flow from other elephant populations. The conservation of Eritrean elephants would benefit from an understanding of their genetic affinities to elephants elsewhere on the continent and the degree to which genetic variation persists in the population. Using dung samples from Eritrean elephants, we examined 18 species-diagnostic single nucleotide polymorphisms in 3 nuclear genes, sequences of mitochondrial HVR1 and ND5, and genotyped 11 microsatellite loci. The sampled Eritrean elephants carried nuclear and mitochondrial DNA markers establishing them as savanna elephants, with closer genetic affinity to Eastern than to North Central savanna elephant populations, and contrary to speculation by some scholars that forest elephants were found in Eritrea. Mitochondrial DNA diversity was relatively low, with 2 haplotypes unique to Eritrea predominating. Microsatellite genotypes could only be determined for a small number of elephants but suggested that the population suffers from low genetic diversity. Conservation efforts should aim to protect Eritrean elephants and their habitat in the short run, with restoration of habitat connectivity and genetic diversity as long-term goals.
C1 [Brandt, Adam L.; Roca, Alfred L.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
[Hagos, Yohannes; Yacob, Yohannes] Minist Agr, Wildlife Conservat Div, Asmera, Eritrea.
[David, Victor A.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Georgiadis, Nicholas J.] Univ Washington, Puget Sound Inst, Tacoma, WA USA.
[Shoshani, Jeheskel] Elephant Res Fdn, Bloomfield Hills, MI 48304 USA.
[Roca, Alfred L.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
RP Roca, AL (reprint author), Univ Illinois, Dept Anim Sci, 1207 West Gregory Dr, Urbana, IL 61801 USA.
EM roca@illinois.edu
RI Brandt, Adam/L-2419-2014;
OI Brandt, Adam L./0000-0002-4604-3327
FU US Fish and Wildlife Service African Elephant Conservation Fund
[AFE-0778-F12AP01143]
FX US Fish and Wildlife Service African Elephant Conservation Fund
(AFE-0778-F12AP01143).
NR 40
TC 5
Z9 5
U1 2
U2 28
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1503
EI 1465-7333
J9 J HERED
JI J. Hered.
PD JAN-FEB
PY 2014
VL 105
IS 1
BP 82
EP 90
DI 10.1093/jhered/est078
PG 9
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 271YP
UT WOS:000328427800008
PM 24285829
ER
PT J
AU Hollevoet, K
Antignani, A
FitzGerald, DJ
Pastan, I
AF Hollevoet, Kevin
Antignani, Antonella
FitzGerald, David J.
Pastan, Ira
TI Combining the Antimesothelin Immunotoxin SS1P With the BH3-mimetic
ABT-737 Induces Cell Death in SS1P-resistant Pancreatic Cancer Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE BH3-mimetic; mesothelin; immunotoxin; pancreatic cancer
ID ANTI-MESOTHELIN IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; RECOMBINANT
IMMUNOTOXIN; MEDIATED APOPTOSIS; CYTOTOXIC ACTIVITY; PHASE-I; THERAPY;
FAMILY; BAK; COMBINATION
AB SS1P is an antimesothelin recombinant immunotoxin (RIT). Pancreatic ductal adenocarcinoma (PDAC) cell lines are resistant to SS1P, despite high mesothelin expression. The aim of this study is to examine whether combining SS1P and BH3-mimetic ABT-737 induces cell death in a panel of PDAC cell lines. ABT-737 binds and neutralizes several antiapoptotic BCL2 family proteins, but has a low affinity for the short-lived MCL1 and BCL2A1. SS1P inhibits protein synthesis, which has shown to downregulate MCL1. PDAC cell lines KLM-1, BxPc-3, and Panc 3.014 were resistant to SS1P or ABT-737 alone. Combining both compounds led to a significant increase in cell death. After 48 hours of treatment, cell death was observed in 92% of KLM-1, 55% of BxPc-3, and 23% of Panc 3.014 cells. Panc 3.014 had the highest number of mesothelin-binding sites (92x10(3)), followed by KLM-1 (58x10(3)) and BxPc-3 (3x10(3)). ABT-737 had no effect on SS1P internalization, but enhanced SS1P-induced protein synthesis inhibition significantly in KLM-1, to a lesser extent in BxPc-3, and very little in Panc 3.014. SS1P alone or in combination with ABT-737 downregulated MCL1 in KLM-1 and BxPc-3, but not in Panc 3.014. Similar observations were made for BCL2A1, which had the highest levels in Panc 3.014. Compared with KLM-1, Panc 3.014, and BxPc-3 also had lower proapoptotic BAK and a trend toward higher MCL1. Proapoptotic BAX was similar in KLM-1 and BxPc-3, but lower in Panc 3.014. In conclusion, combining SS1P with ABT-737 overcomes SS1P-resistance in PDAC, although to a variable extent. The efficacy of the combination is mainly associated with the RIT-associated inhibition of protein synthesis and the ability to downregulate MCL1 and BCL2A1, while levels of other key apoptotic proteins may also be important. Our data support the combination of an RIT and a BH3-mimetic, and identify factors that potentially limit the efficacy of such therapeutic approach.
C1 [Hollevoet, Kevin; Antignani, Antonella; FitzGerald, David J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU National Institutes of Health, NCI, CCR
FX Supported by the Intramural Research Program of the National Institutes
of Health, NCI, CCR.
NR 35
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U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD JAN
PY 2014
VL 37
IS 1
BP 8
EP 15
DI 10.1097/CJI.0000000000000010
PG 8
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 275UK
UT WOS:000328703100002
PM 24316551
ER
PT J
AU Nawaz, AA
Zhang, XJ
Mao, XL
Rufo, J
Lin, SCS
Guo, F
Zhao, YH
Lapsley, M
Li, P
McCoy, JP
Levine, SJ
Huang, TJ
AF Nawaz, Ahmad Ahsan
Zhang, Xiangjun
Mao, Xiaole
Rufo, Joseph
Lin, Sz-Chin Steven
Guo, Feng
Zhao, Yanhui
Lapsley, Michael
Li, Peng
McCoy, J. Philip
Levine, Stewart J.
Huang, Tony Jun
TI Sub-micrometer-precision, three-dimensional (3D) hydrodynamic focusing
via "microfluidic drifting"
SO LAB ON A CHIP
LA English
DT Article
ID ON-A-CHIP; POLYDIMETHYLSILOXANE PDMS MICROCHANNELS; ACOUSTIC-WAVES SSAW;
FLOW-CYTOMETRY; CELL-CYCLE; DEVICES; PARTICLES; LIGHT; TECHNOLOGY;
PRINCIPLES
AB In this article, we demonstrate single-layered, "microfluidic drifting" based three-dimensional (3D) hydrodynamic focusing devices with particle/cell focal positioning approaching submicron precision along both lateral and vertical directions. By systematically optimizing channel geometries and sample/sheath flow rates, a series of "microfluidic drifting" based 3D hydrodynamic focusing devices with different curvature angles are designed and fabricated. Their performances are then evaluated using confocal microscopy, fast camera imaging, and side-view imaging techniques. Using a device with a curvature angle of 180, we have achieved a standard deviation of +/- 0.45 mu m in particle focal position and a coefficient of variation (CV) of 2.37% in flow cytometric measurements. To the best of our knowledge, this is the best CV that has been achieved using a microfluidic flow cytometry device. Moreover, the device showed the capability to distinguish 8 peaks when subjected to a stringent 8-peak rainbow calibration test, signifying the ability to perform sensitive, accurate tests similar to commercial flow cytometers. We have further tested and validated our device by detection of HEK-293 cells. With its advantages in simple fabrication (i.e., single-layered device), precise 3D hydrodynamic focusing (i.e., submicrometer precision along both lateral and vertical directions), and high detection resolution (i.e., low CV), our method could serve as an important basis for high-performance, mass-producible microfluidic flow cytometry.
C1 [Nawaz, Ahmad Ahsan; Mao, Xiaole; Rufo, Joseph; Lin, Sz-Chin Steven; Guo, Feng; Zhao, Yanhui; Lapsley, Michael; Li, Peng; Huang, Tony Jun] Penn State Univ, Dept Engn Sci & Mech, University Pk, PA 16802 USA.
[Zhang, Xiangjun] Tsinghua Univ, State Key Lab Tribol, Beijing 100084, Peoples R China.
[Mao, Xiaole; Huang, Tony Jun] Penn State Univ, Dept Bioengn, University Pk, PA 16802 USA.
[McCoy, J. Philip; Levine, Stewart J.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Huang, TJ (reprint author), Penn State Univ, Dept Engn Sci & Mech, 227 Hammond Bldg, University Pk, PA 16802 USA.
EM junhuang@psu.edu
RI Zhao, Yanhui/D-3926-2011; Li, Peng/B-3054-2013; Guo, Feng/B-6860-2012;
Huang, Tony/A-1546-2009
OI Zhao, Yanhui/0000-0003-1131-8527; Li, Peng/0000-0002-8332-7142; Guo,
Feng/0000-0001-9103-3235;
FU National Institutes of Health [1DP2OD007209-01]; American Asthma
Foundation; National Science Foundation [ECCS-0824183, ECCS-0801922];
Penn State Center for Nanoscale Science (MRSEC) [DMR-0820404]; NHLBI
Division of Intramural Research; NSF
FX We thank Missy Hazen, Ruth Nissly, Vincent Crespi, Daniel Ahmed, and
Justin Kiehne for the technical help with instrumentation and helpful
discussions. This research was supported by the National Institutes of
Health (1DP2OD007209-01), an American Asthma Foundation Scholar Award,
the National Science Foundation (ECCS-0824183 and ECCS-0801922), and the
Penn State Center for Nanoscale Science (MRSEC) under grant DMR-0820404.
J.P.M. and S.J.L. are supported by the NHLBI Division of Intramural
Research. Components of this work were conducted at the Penn State node
of the NSF-funded National Nanotechnology Infrastructure Network.
NR 61
TC 21
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U1 4
U2 48
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1473-0197
EI 1473-0189
J9 LAB CHIP
JI Lab Chip
PY 2014
VL 14
IS 2
BP 415
EP 423
DI 10.1039/c3lc50810b
PG 9
WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience
& Nanotechnology
SC Biochemistry & Molecular Biology; Chemistry; Science & Technology -
Other Topics
GA 278ST
UT WOS:000328910700018
PM 24287742
ER
PT J
AU Eliav, U
Komlosh, ME
Basser, PJ
Navon, G
AF Eliav, Uzi
Komlosh, Michal E.
Basser, Peter J.
Navon, Gil
TI Collagen Composition and Content-Dependent Contrast in Porcine Annulus
Fibrosus Achieved by Using Double Quantum and Magnetization Transfer
Filtered UTE MRI
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE interverterbral disc; annulus fibrosus; collagen type I; collagen type
II; double quantum filter; magnetization transfer; ultra-short TE
ID DIPOLAR INTERACTIONS; TENDON; WATER; RELAXATION; CARTILAGE; TISSUES;
ORIENTATION; RESONANCE; EXCHANGE
AB PurposeTo test the potential of combining double quantum and magnetization transfer filtered ultra-short echo time (DQF-MT-UTE) MRI to obtain information about the macromolecular composition and characteristics of connective tissues.
MethodsA DQF-MT-UTE pulse sequence was implemented on a 14.1 T AVANCE III Bruker spectrometer equipped with a Bruker micro2.5-imaging gradient system to obtain images of porcine annulus fibrosus.
ResultsThe DQF-MT-UTE MRI of the annulus fibrosus of porcine intervertebral disc, where the creation time of the double quantum coherence filtering (DQF) was on a time scale appropriate for excitation of macromolecules, showed stronger signal from the outer layers of the disc than from the inner layers closer to the nucleus pulposus. Similarly, spectroscopic studies showed the same trend in the efficiency of the magnetization transfer (MT) from collagen to water.
ConclusionDQF-MT filtered UTE MRI of the annulus fibrosus provides new contrast parameters that depend on the concentration of the collagen and on the rate and efficiency of MT of its protons to water. The latter parameters appear to be different for collagen types I and II in the annulus fibrosus. Magn Reson Med 71:388-393, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Eliav, Uzi; Navon, Gil] Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel.
[Komlosh, Michal E.; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, STBB, Bethesda, MD USA.
[Komlosh, Michal E.] Ctr Neuroregenerat Med CNRM, Bethesda, MD USA.
[Komlosh, Michal E.] Henry Jackson Fdn, Bethesda, MD USA.
RP Navon, G (reprint author), Tel Aviv Univ, Sch Chem, Haim Levanon St, IL-69978 Tel Aviv, Israel.
EM navon@post.tau.ac.il
FU US-Israel Binational Science Foundation [2007157]; European FP7 program
ENCITE; Israel Ministry of Science and Technology [3-6446]; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, Center for Regenerative Medicine within the US Department
of Defense
FX Grant sponsor: US-Israel Binational Science Foundation; Grant number:
2007157; Grant sponsor: European FP7 program ENCITE; Grant sponsor:
Israel Ministry of Science and Technology; Grant number: 3-6446; Grant
sponsors: Intramural Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, Center for Regenerative
Medicine within the US Department of Defense.
NR 17
TC 2
Z9 3
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JAN
PY 2014
VL 71
IS 1
BP 388
EP 393
DI 10.1002/mrm.24662
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 274BO
UT WOS:000328580300044
PM 23413021
ER
PT J
AU White, KL
Scopton, AP
Rives, ML
Bikbulatov, RV
Polepally, PR
Brown, PJ
Kenakin, T
Javitch, JA
Zjawiony, JK
Roth, BL
AF White, Kate L.
Scopton, Alex P.
Rives, Marie-Laure
Bikbulatov, Ruslan V.
Polepally, Prabhakar R.
Brown, Peter J.
Kenakin, Terrance
Javitch, Jonathan A.
Zjawiony, Jordan K.
Roth, Bryan L.
TI Identification of Novel Functionally Selective kappa-Opioid Receptor
Scaffolds
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID SEROTONIN RECEPTORS; INDEPENDENT INTERNALIZATION; SIGNAL-TRANSDUCTION;
SALVINORIN-A; IN-VIVO; AGONIST; ACTIVATION; ARRESTIN; STRESS;
TRAFFICKING
AB The kappa-opioid receptor (KOR)-dynorphin system has been implicated in the control of affect, cognition, and motivation, and is thought to be dysregulated in mood and psychotic disorders, as well as in various phases of opioid dependence. KOR agonists exhibit analgesic effects, although the adverse effects produced by some KOR agonists, including sedation, dysphoria, and hallucinations, have limited their clinical use. Interestingly, KOR-mediated dysphoria, assessed in rodents as aversion, has recently been attributed to the activation of the p38 mitogen-activated protein kinase pathway following arrestin recruitment to the activated KOR. Therefore, KOR-selective G protein-biased agonists, which do not recruit arrestin, have been proposed to be more effective analgesics, without the adverse effects triggered by the arrestin pathway. As an initial step toward identifying novel biased KOR agonists, we applied a multifaceted screening strategy utilizing both in silico and parallel screening approaches. We identified several KOR-selective ligand scaffolds with a range of signaling bias in vitro. The arylacetamide-based scaffold includes both G protein-and beta-arrestin-biased ligands, while the endogenous peptides and the diterpene scaffolds are G protein biased. Interestingly, we found scaffold screening to be more successful than library screening in identifying biased ligands. Many of the identified functionally selective ligands are potent selective KOR agonists that are reported to be active in the central nervous system. They therefore represent excellent candidates for in vivo studies aiming at determining the behavioral effects mediated by specific KOR-mediated signaling cascades.
C1 [White, Kate L.; Kenakin, Terrance; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA.
[Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC USA.
[Rives, Marie-Laure; Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Javitch, Jonathan A.] Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY USA.
[Rives, Marie-Laure; Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, New York Div Mol Therapeut, New York, NY 10032 USA.
[Bikbulatov, Ruslan V.; Polepally, Prabhakar R.; Zjawiony, Jordan K.] Univ Mississippi, Dept Pharmacognosy, University, MS 38677 USA.
[Scopton, Alex P.; Brown, Peter J.] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
RP Roth, BL (reprint author), UNC Dept Pharmacol, 4009 Genet Med CB 7365, Chapel Hill, NC 27599 USA.
EM bryan_roth@med.unc.edu
RI Polepally, Prabhakar /G-9202-2014; Roth, Bryan/F-3928-2010
FU National Institutes of Health National Institute on Drug Abuse; National
Institute of Mental Health [RO1DA01724, U19MH82441, K05DA022413,
R01MH54137]; National Institute on Drug Abuse EUREKA Grant
[R01DA027170]; National Institute of Mental Health Psychoactive Drug
Screening Program; AbbVie; Boehringer Ingelheim; Canada Foundation for
Innovation; Canadian Institutes for Health Research; Genome Canada
through the Ontario Genomics Institute [OGI-055]; GlaxoSmithKline;
Janssen; Lilly Canada; Novartis Research Foundation; Ontario Ministry of
Economic Development and Innovation; Pfizer; Takeda; Wellcome Trust
[092809/Z/10/Z]
FX The work was funded by the National Institutes of Health National
Institute on Drug Abuse and National Institute of Mental Health [Grants
RO1DA01724, U19MH82441, K05DA022413, and R01MH54137]; a National
Institute on Drug Abuse EUREKA Grant [R01DA027170]; and the National
Institute of Mental Health Psychoactive Drug Screening Program. The
Structural Genomics Consortium is a registered charity (No. 1097737)
that receives funds from AbbVie, Boehringer Ingelheim, the Canada
Foundation for Innovation, the Canadian Institutes for Health Research,
Genome Canada through the Ontario Genomics Institute [OGI-055],
GlaxoSmithKline, Janssen, Lilly Canada, the Novartis Research
Foundation, the Ontario Ministry of Economic Development and Innovation,
Pfizer, Takeda, and the Wellcome Trust [092809/Z/10/Z].
NR 49
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U1 1
U2 24
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JAN
PY 2014
VL 85
IS 1
BP 83
EP 90
DI 10.1124/mol.113.089649
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 278KS
UT WOS:000328889800009
PM 24113749
ER
PT J
AU Wang, XX
Ni, L
Yang, L
Duan, QL
Chen, C
Edin, ML
Zeldin, DC
Wang, DW
AF Wang, Xingxu
Ni, Li
Yang, Lei
Duan, Quanlu
Chen, Chen
Edin, Matthew L.
Zeldin, Darryl C.
Wang, Dao Wen
TI CYP2J2-Derived Epoxyeicosatrienoic Acids Suppress Endoplasmic Reticulum
Stress in Heart Failure
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID OXIDE-INDUCED VASODILATATION; CARDIAC MYOCYTE APOPTOSIS;
NECROSIS-FACTOR-ALPHA; OXYGEN FREE-RADICALS; NITRIC-OXIDE;
CALCIUM-ATPASE; DILATED CARDIOMYOPATHY; CONTRACTILE FUNCTION;
GLUCOSE-HOMEOSTASIS; S-GLUTATHIOLATION
AB Prolonged endoplasmic reticulum (ER) stress causes apoptosis and is associated with heart failure. Whether CYP2J2 and its arachidonic acid metabolites [epoxyeicosatrienoic acids (EETs)] have a protective influence on ER stress and heart failure has not been studied. Assays of myocardial samples from patients with end-stage heart failure showed evidence of ER stress. Chronic infusion of isoproterenol (ISO) or angiotensin II (AngII) by osmotic mini-pump induced cardiac hypertrophy and heart failure in mice as evaluated by hemodynamic measurements and echocardiography. Interestingly, transgenic (Tr) mice with cardiomyocyte-specific CYP2J2 expression were protected against heart failure compared with wild-type mice. ISO or AngII administration induced ER stress and apoptosis, and increased levels of intracellular Ca2+. These phenotypes were abolished by CYP2J2 overexpression in vivo or exogenous EETs treatment of cardiomyocytes in vitro. ISO or AngII reduced sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) expression in hearts or isolated cardiomyocytes; however, loss of SERCA2a expression was prevented in CYP2J2 Tr hearts in vivo or in cardiomyocytes treated with EETs in vitro. The reduction of SERCA2a activity was concomitant with increased oxidation of SERCA2a. EETs reversed SERCA2a oxidation through increased expression of antioxidant enzymes and reduced reactive oxygen species levels. Tempol, a membrane-permeable radical scavenger, similarly decreased oxidized SERCA2a levels, restored SERCA2a activity, and markedly reduced ER stress response in the mice treated with ISO. In conclusion, CYP2J2-derived EETs suppress ER stress response in the heart and protect against cardiac failure by maintaining intracellular Ca2+ homeostasis and SERCA2a expression and activity.
C1 [Wang, Xingxu; Ni, Li; Yang, Lei; Duan, Quanlu; Chen, Chen; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Internal Med, Inst Hypertens,Tongji Hosp, Wuhan 430030, Peoples R China.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Internal Med, Inst Hypertens,Tongji Hosp, 1095 Jiefang Ave, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
RI Chen, Chen/B-2080-2014;
OI Edin, Matthew/0000-0002-7042-500X
FU National 973 Program [2012CB518004]; National Natural Science Foundation
of China [31130031, 30930039, 81000097, 30770882]; Intramural Research
Program of the National Institutes of Health [National Institute of
Environmental Health Sciences] [Z01-ES025034]
FX This work was supported by the National 973 Program [Grant 2012CB518004]
and the National Natural Science Foundation of China [Grants 31130031,
30930039, 81000097, and 30770882]. This work was also supported, in
part, by the Intramural Research Program of the National Institutes of
Health [National Institute of Environmental Health Sciences] [Grant
Z01-ES025034].
NR 56
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Z9 22
U1 0
U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JAN
PY 2014
VL 85
IS 1
BP 105
EP 115
DI 10.1124/mol.113.087122
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 278KS
UT WOS:000328889800011
PM 24145329
ER
PT J
AU Virtanen, JO
Wohler, J
Fenton, K
Reich, DS
Jacobson, S
AF Virtanen, J. O.
Wohler, J.
Fenton, K.
Reich, D. S.
Jacobson, S.
TI Oligoclonal bands in multiple sclerosis reactive against two
herpesviruses and association with magnetic resonance imaging findings
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE Multiple sclerosis; magnetic resonance imaging; immunology
ID EPSTEIN-BARR-VIRUS; CEREBROSPINAL-FLUID; IMMUNE-RESPONSE;
CHLAMYDIA-PNEUMONIAE; HUMAN-HERPESVIRUS-6; ANTIBODIES; INFECTION; BRAIN;
DNA; EBV
AB Background: Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS).
Objective: The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS.
Methods: The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated.
Results: Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs).
Conclusion: The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS.
C1 [Virtanen, J. O.; Wohler, J.; Fenton, K.; Reich, D. S.; Jacobson, S.] NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA.
RP Virtanen, JO (reprint author), NINDS, 9000 Rockville Pike,Bldg 10,Room 5C-103, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU NINDS Intramural Program; Academy of Finland; Orion-Farmos Foundation;
Instrumentarium Science Foundation
FX This study was funded by NINDS Intramural Program. JO Virtanen has been
supported by the Academy of Finland, Orion-Farmos Foundation and
Instrumentarium Science Foundation.
NR 36
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Z9 10
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD JAN
PY 2014
VL 20
IS 1
BP 27
EP 34
DI 10.1177/1352458513490545
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 274LL
UT WOS:000328607800007
PM 23722324
ER
PT J
AU Gaitan, MI
Maggi, P
Wohler, J
Leibovitch, E
Sati, P
Calandri, IL
Merkle, H
Massacesi, L
Silva, AC
Jacobson, S
Reich, DS
AF Gaitan, Maria I.
Maggi, Pietro
Wohler, Jillian
Leibovitch, Emily
Sati, Pascal
Calandri, Ismael L.
Merkle, Hellmut
Massacesi, Luca
Silva, Afonso C.
Jacobson, Steven
Reich, Daniel S.
TI Perivenular brain lesions in a primate multiple sclerosis model at
7-tesla magnetic resonance imaging
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE Veins; multiple sclerosis; experimental autoimmune encephalomyelitis;
magnetic resonance imaging; susceptibility weighted imaging
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MS LESIONS; PARENCHYMAL
VEINS; COMMON MARMOSETS; IRON DEPOSITION; DEMYELINATION
AB Background Magnetic resonance imaging (MRI) can provide in vivo assessment of tissue damage, allowing evaluation of multiple sclerosis (MS) lesion evolution over time - a perspective not obtainable with postmortem histopathology. Relapsing-remitting experimental autoimmune encephalomyelitis (EAE) is an experimental model of MS that can be induced in the common marmoset, a small new world primate, and that causes perivenular white matter (WM) lesions similar to those observed in MS.
Methods Brain lesion development and evolution were studied in vivo and postmortem in four marmosets with EAE through serial T2- and T2*-weighted scans at 7-tesla. Supratentorial WM lesions were identified and characterized.
Results Of 97 lesions observed, 86 (88%) were clearly perivenular, and 62 (72%) developed around veins that were visible even prior to EAE induction. The perivenular configuration was confirmed by postmortem histopathology. Most affected veins, and their related perivascular Virchow-Robin spaces, passed into the subarachnoid space rather than the ventricles.
Conclusion As in human MS, the intimate association between small veins and EAE lesions in the marmoset can be studied with serial in vivo MRI. This further strengthens the usefulness of this model for understanding the process of perivenular lesion development and accompanying tissue destruction in MS.
C1 [Gaitan, Maria I.; Maggi, Pietro; Sati, Pascal; Massacesi, Luca; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA.
[Gaitan, Maria I.; Calandri, Ismael L.] FLENI, Inst Neurol Res Dr Raul Carrea, Dept Neurol, Buenos Aires, DF, Argentina.
[Maggi, Pietro; Massacesi, Luca] Univ Florence, Dept Neurol & Psychiat Sci, I-50121 Florence, Italy.
[Wohler, Jillian; Leibovitch, Emily; Jacobson, Steven] NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA.
[Merkle, Hellmut; Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Bethesda, MD 20892 USA.
RP Reich, DS (reprint author), NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, 10 Ctr Dr MSC 1400,Bldg 10,Room 5C103, Bethesda, MD 20892 USA.
EM daniel.reich@nih.gov
RI Reich, Daniel/E-5701-2010;
OI Reich, Daniel/0000-0002-2628-4334; Massacesi, Luca/0000-0001-5083-372X
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 19
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U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD JAN
PY 2014
VL 20
IS 1
BP 64
EP 71
DI 10.1177/1352458513492244
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 274LL
UT WOS:000328607800012
PM 23773983
ER
PT J
AU Bough, KJ
Amur, S
Lao, GF
Hemby, SE
Tannu, NS
Kampman, KM
Schmitz, JM
Martinez, D
Merchant, KM
Green, C
Sharma, J
Dougherty, AH
Moeller, FG
AF Bough, Kristopher J.
Amur, Shashi
Lao, Guifang
Hemby, Scott E.
Tannu, Nilesh S.
Kampman, Kyle M.
Schmitz, Joy M.
Martinez, Diana
Merchant, Kalpana M.
Green, Charles
Sharma, Jyoti
Dougherty, Anne H.
Moeller, F. Gerard
TI Biomarkers for the Development of New Medications for Cocaine Dependence
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Review
DE biomarkers; cocaine dependence; drug development tools; addiction
ID WHITE-MATTER INTEGRITY; DOPAMINE-BETA-HYDROXYLASE; NUCLEUS-ACCUMBENS;
GENE-EXPRESSION; HUMAN BRAIN; DRUG-ABUSE; ABSTINENCE SYMPTOMATOLOGY;
MECHANISTIC BIOMARKERS; INDIVIDUAL-DIFFERENCES; MYOCARDIAL-INFARCTION
AB There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)-another type of defined DDT-is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.
C1 [Bough, Kristopher J.] NIDA, Div Basic Neurosci & Behav Res, Bethesda, MD 20892 USA.
[Amur, Shashi] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Lao, Guifang] NIDA, Div Pharmacotherapies & Med Consequences, Bethesda, MD 20892 USA.
[Hemby, Scott E.] Wake Forest Univ, Dept Physiol & Pharmacol, Winston Salem, NC 27109 USA.
[Tannu, Nilesh S.] Univ Texas Houston, Sch Med, Dept Psychiat & Behav Sci, Houston, TX USA.
[Kampman, Kyle M.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Schmitz, Joy M.] Univ Texas Houston, Sch Med, Dept Psychiat & Behav Sci, Houston, TX USA.
[Martinez, Diana] Columbia Univ, Dept Psychiat, New York, NY USA.
[Martinez, Diana] New York State Univ, Dept Psychiat, New York, NY USA.
[Merchant, Kalpana M.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Green, Charles] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
[Sharma, Jyoti; Dougherty, Anne H.] Univ Texas Houston, Sch Med, Dept Cardiovasc Med, Houston, TX USA.
[Moeller, F. Gerard] Virginia Commonwealth Univ, Sch Med, Dept Psychiat & Pharmacol & Toxicol, Richmond, VA 23219 USA.
RP Moeller, FG (reprint author), Virginia Commonwealth Univ, Dept Psychiat & Pharmacol & Toxicol, 203 E Cary St,Suite 202, Richmond, VA 23219 USA.
EM fgmoeller@vcu.edu
FU NIDA NIH HHS [P50 DA006634, R01 DA012498, U54 DA039002]
NR 96
TC 10
Z9 10
U1 3
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2014
VL 39
IS 1
BP 202
EP 219
DI 10.1038/npp.2013.210
PG 18
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 274DD
UT WOS:000328584500013
PM 23979119
ER
PT J
AU Colvis, CM
Austin, CP
AF Colvis, Christine M.
Austin, Christopher P.
TI Innovation in Therapeutics Development at the NCATS
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Editorial Material
C1 [Colvis, Christine M.; Austin, Christopher P.] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD 20892 USA.
RP Colvis, CM (reprint author), Natl Ctr Adv Translat Sci, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM ccolvis@mail.nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2014
VL 39
IS 1
BP 230
EP 232
DI 10.1038/npp.2013.247
PG 3
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 274DD
UT WOS:000328584500015
PM 24317308
ER
PT J
AU Uhl, GR
Drgonova, J
AF Uhl, George R.
Drgonova, Jana
TI Cell Adhesion Molecules: Druggable Targets for Modulating the Connectome
and Brain Disorders?
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Editorial Material
ID ADDICTION; DELTA
C1 [Uhl, George R.; Drgonova, Jana] NIDA, NIH IRP, Mol Neurobiol Branch, Baltimore, MD 21224 USA.
RP Uhl, GR (reprint author), NIDA, NIH IRP, Mol Neurobiol Branch, Baltimore, MD 21224 USA.
EM guhl@intra.nida.nih.gov
FU Intramural NIH HHS
NR 6
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Z9 7
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2014
VL 39
IS 1
BP 235
EP 235
DI 10.1038/npp.2013.240
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 274DD
UT WOS:000328584500018
PM 24317312
ER
PT J
AU Brady, LS
Potter, WZ
AF Brady, Linda S.
Potter, William Z.
TI Proteomic Biomarkers for Brain Disorders: Technical Considerations and
Challenges
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Editorial Material
ID DISEASE
C1 [Brady, Linda S.] NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
[Potter, William Z.] NIMH, Bethesda, MD 20892 USA.
RP Brady, LS (reprint author), NIMH, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA.
EM lbrady@mail.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2014
VL 39
IS 1
BP 252
EP 252
DI 10.1038/npp.2013.202
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 274DD
UT WOS:000328584500033
PM 24317326
ER
PT J
AU Wise, RA
Koob, GF
AF Wise, Roy A.
Koob, George F.
TI The Development and Maintenance of Drug Addiction
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE substance abuse; dependence; motivation; incentive
ID KAPPA-OPIOID RECEPTOR; DOPAMINERGIC NEURONAL-ACTIVITY; INDUCED
BEHAVIORAL-RESPONSES; NUCLEUS-ACCUMBENS DOPAMINE; MOLECULAR-MECHANISMS;
COCAINE-SEEKING; PSYCHOLOGICAL DEPENDENCE; NEUROBIOLOGICAL EVIDENCE;
WITHDRAWAL SYNDROME; INTRAVENOUS HEROIN
C1 [Wise, Roy A.] Natl Inst Drug Abuse, Dept Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
RP Wise, RA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 251 Bayview Blvd,5500 Nathan Shock Dr,Suite 2000, Baltimore, MD 21224 USA.
EM rwise@intra.nida.nih.gov
RI koob, george/P-8791-2016
FU National Inistitutes of Health [AA006420]
FX Preparation of this essay was supported by the Intramural Research
Program (RW) and extramural grant AA006420 (GFK) from the National
Inistitutes of Health. Dr Wise and Dr Koob declare no potential conflict
of interest.
NR 102
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Z9 76
U1 6
U2 126
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2014
VL 39
IS 2
BP 254
EP 262
DI 10.1038/npp.2013.261
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 274DM
UT WOS:000328585400002
PM 24121188
ER
PT J
AU Cassataro, D
Bergfeldt, D
Malekian, C
Van Snellenberg, JX
Thanos, PK
Fishell, G
Sjulson, L
AF Cassataro, Daniela
Bergfeldt, Daniella
Malekian, Cariz
Van Snellenberg, Jared X.
Thanos, Panayotis K.
Fishell, Gord
Sjulson, Lucas
TI Reverse Pharmacogenetic Modulation of the Nucleus Accumbens Reduces
Ethanol Consumption in a Limited Access Paradigm
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE alcohol dependence; reverse pharmacogenetics; nucleus accumbens;
drinking in the dark; DREADDs
ID PROTEIN-COUPLED RECEPTORS; STEREOTACTIC SURGERY; ALCOHOL-CONSUMPTION;
REMOTE-CONTROL; C57BL/6J MICE; GENE-TRANSFER; DRINKING; MODEL;
OVEREXPRESSION; EXPRESSION
AB Bilateral stereotactic lesioning of the nucleus accumbens (NAc) core reduces relapse rates in alcohol-dependent patients but may cause irreversible cognitive deficits. Deep brain stimulation has similar effects but requires costly implanted hardware and regular surgical maintenance. Therefore, there is considerable interest in refining these approaches to develop reversible, minimally invasive treatments for alcohol dependence. Toward this end, we evaluated the feasibility of a reverse pharmacogenetic approach in a preclinical mouse model. We first assessed the predictive validity of a limited access ethanol consumption paradigm by confirming that electrolytic lesions of the NAc core decreased ethanol consumption, recapitulating the effects of similar lesions in humans. We then used this paradigm to test the effect of modulating activity in the NAc using the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) hM3Dq and hM4Di. We found that increasing activity with hM3Dq had no effect, but suppressing activity with hM4Di reduced alcohol consumption to a similar extent as lesioning without affecting consumption of water or sucrose. These results may represent early steps toward a novel neurosurgical treatment modality for alcohol dependence that is reversible and externally titratable, yet highly targetable and less invasive than current approaches such as lesioning or deep brain stimulation.
C1 [Cassataro, Daniela; Sjulson, Lucas] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA.
[Cassataro, Daniela; Bergfeldt, Daniella; Malekian, Cariz; Fishell, Gord; Sjulson, Lucas] NYU, Inst Neurosci, Dept Neurosci & Physiol, Smilow Neurosci Program, New York, NY USA.
[Bergfeldt, Daniella] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.
[Malekian, Cariz] Uppsala Univ, Uppsala Biomed Ctr, Dept Med, Polacksbacken, Sweden.
[Van Snellenberg, Jared X.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, Div Translat Imaging, New York, NY 10032 USA.
[Thanos, Panayotis K.] NIAAA, Neuroimaging Lab, Intramural Program, NIH, Bethesda, MD USA.
[Thanos, Panayotis K.] Brookhaven Natl Lab, Dept Med, Behav Pharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
RP Sjulson, L (reprint author), NYU, Sch Med, Dept Psychiat, Smilow 507,522 1st Ave, New York, NY 10016 USA.
EM Lucas.Sjulson@nyumc.org
RI Van Snellenberg, Jared/F-7889-2013
OI Van Snellenberg, Jared/0000-0003-2442-2008
FU NINDS; NYU Physician Scientist Training Program; NYU Dean's
Undergraduate Research Fund; NIH [R01 MH068469, R01 MH071679, R01
MH095147, R01 NS081297]; National Center for Advancing Translational
Sciences, National Institutes of Health [UL1 TR000038]
FX We thank Michael Krashes, Brad Lowell, Bryan Roth, and Jurgen Wess for
sharing DREADD constructs and reagents. CNO was obtained from the NIH as
part of the Rapid Access to Investigative Drug Program funded by the
NINDS. We also thank Michael Long and Dmitriy Aronov for advice on
electrolytic lesions, Charles Hoeffer and the NYU rodent behavior core
facility for help with behavioral assays, and Jens Hjerling-Leffler for
valuable comments on the manuscript. This work was supported by funds
from the NYU Physician Scientist Training Program (LS); the NYU Dean's
Undergraduate Research Fund (DC); NIH grants R01 MH068469, R01 MH071679,
R01 MH095147, and R01 NS081297 to GF; and grant UL1 TR000038 from the
National Center for Advancing Translational Sciences, National
Institutes of Health.
NR 36
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U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JAN
PY 2014
VL 39
IS 2
BP 283
EP 290
DI 10.1038/npp.2013.184
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 274DM
UT WOS:000328585400005
PM 23903031
ER
PT J
AU Lonsdorf, E
Travis, D
Ssuna, R
Lantz, E
Wilson, M
Gamble, K
Terio, K
Leendertz, F
Ehlers, B
Keele, B
Hahn, B
Gillespie, T
Pond, J
Raphael, J
Collins, A
AF Lonsdorf, Elizabeth
Travis, Dominic
Ssuna, Richard
Lantz, Emma
Wilson, Michael
Gamble, Kathryn
Terio, Karen
Leendertz, Fabian
Ehlers, Bernhard
Keele, Brandon
Hahn, Beatrice
Gillespie, Thomas
Pond, Joel
Raphael, Jane
Collins, Anthony
TI Field immobilization for treatment of an unknown illness in a wild
chimpanzee (Pan troglodytes schweinfurthii) at Gombe National Park,
Tanzania: findings, challenges, and lessons learned
SO PRIMATES
LA English
DT Article
DE Apes; Health; Disease; Intervention; Diagnostics
ID MOUNTAIN GORILLAS; CAPTIVE CHIMPANZEES; POPULATION-DYNAMICS;
INFECTIOUS-DISEASES; RAIN-FOREST; GREAT APES; PRIMATES; ADENOVIRUSES;
CONSERVATION; HUMANS
AB Infectious diseases are widely presumed to be one of the greatest threats to ape conservation in the wild. Human diseases are of particular concern, and the costs and benefits of human presence in protected areas with apes are regularly debated. While numerous syndromes with fatal outcomes have recently been described, precise identification of pathogens remains difficult. These diagnostic difficulties are compounded by the fact that direct veterinary intervention on wild apes is quite rare. Here we present the unique case of a wild chimpanzee at Gombe National Park that was observed with a severe illness and was subsequently examined and treated in the field. Multiple specimens were collected and tested with the aim of identifying the pathogen responsible for the illness. Our findings represent the first extensive screening of a living wild chimpanzee, yet despite our efforts, the cause and source of illness remain unknown. Nevertheless, our findings represent valuable baseline data for the ape conservation community and for comparison with other recent findings. In addition, we present the case here to demonstrate the planning required and multiple types of expertise necessary to maximize the amount of data obtained from such a rare intervention, and to provide lessons learned for future studies.
C1 [Lonsdorf, Elizabeth] Franklin & Marshall Coll, Dept Psychol, Lancaster, PA 17604 USA.
[Lonsdorf, Elizabeth; Travis, Dominic; Lantz, Emma; Gamble, Kathryn; Pond, Joel; Raphael, Jane] Lincoln Pk Zoo, Conservat Programs, Chicago, IL USA.
[Wilson, Michael] Univ Minnesota, Dept Anthropol, Minneapolis, MN USA.
[Wilson, Michael] Univ Minnesota, Dept Ecol Evolut & Behav, Minneapolis, MN 55455 USA.
[Terio, Karen] Univ Illinois, Zoo Pathol Program, Maywood, IL USA.
[Leendertz, Fabian; Ehlers, Bernhard] Robert Koch Inst, Berlin, Germany.
[Keele, Brandon] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Hahn, Beatrice] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Gillespie, Thomas] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA.
[Gillespie, Thomas] Emory Univ, Program Populat Biol Ecol & Evolut, Atlanta, GA 30322 USA.
[Gillespie, Thomas] Emory Univ, Dept Environm Hlth, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Raphael, Jane; Collins, Anthony] Gombe Stream Res Ctr, Kigoma, Tanzania.
[Collins, Anthony] Jane Goodall Inst, Arlington, VA USA.
RP Lonsdorf, E (reprint author), Franklin & Marshall Coll, Dept Psychol, POB 3003, Lancaster, PA 17604 USA.
EM elizabeth.lonsdorf@fandm.edu
FU Jane Goodall Institute; Tanzania National Parks (TANAPA); US Fish and
Wildlife Great Ape Conservation Fund; Arcus Foundation; National
Institutes of Health [R01 AI58715]; Government of Tanzania; Tanzania
National Parks; Tanzania Commission for Science and Technology; Tanzania
Wildlife Research Institute
FX The authors thank the Jane Goodall Institute and Tanzania National Parks
(TANAPA) for initiating and continuing the over 50-year research
tradition at Gombe, including providing support for the current
health-monitoring project. In addition we thank the field staff,
especially Baraka Gilagiza and Matendo Msafiri for assistance during the
intervention, and Bill Wallauer and Kristin Mosher at the Gombe Stream
Research Centre for collecting behavioral data. We are grateful to Dr.
Wayne Berry for viewing video and providing a neurological assessment.
Permission and support to carry out research at Gombe were granted by
the Government of Tanzania, Tanzania National Parks, Tanzania Commission
for Science and Technology, and Tanzania Wildlife Research Institute. We
thank Yingying Li for technical assistance, Liv Kismartoni for
logistical assistance, and Emma Finestone for editorial assistance.
Thanks are also due to two anonymous reviewers whose comments greatly
improved this manuscript. Samples were imported in accordance with
Convention on International Trade in Endangered Species of Wild Fauna
and Flora regulations. This work was supported by grants from the US
Fish and Wildlife Great Ape Conservation Fund, the Arcus Foundation, and
the National Institutes of Health (R01 AI58715).
NR 54
TC 1
Z9 1
U1 2
U2 17
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 0032-8332
EI 1610-7365
J9 PRIMATES
JI Primates
PD JAN
PY 2014
VL 55
IS 1
BP 89
EP 99
DI 10.1007/s10329-013-0372-4
PG 11
WC Zoology
SC Zoology
GA 278RL
UT WOS:000328907300012
PM 23872909
ER
PT J
AU Chen, YW
Zhao, HY
Schuck, P
Wistow, G
AF Chen, Yingwei
Zhao, Huaying
Schuck, Peter
Wistow, Graeme
TI Solution properties of gamma-crystallins: Compact structure and low
frictional ratio are conserved properties of diverse gamma-crystallins
SO PROTEIN SCIENCE
LA English
DT Article
DE crystallin; protein evolution; protein stability; solution behavior
ID OPTICAL COHERENCE TOMOGRAPHY; EYE LENS TRANSPARENCY; SEQUENCE TAG
ANALYSIS; S-CRYSTALLIN; CATARACT; PROTEINS; MUTATION; NEIBANK; DOMAIN;
KEY
AB gamma-crystallins are highly specialized proteins of the vertebrate eye lens where they survive without turnover under high molecular crowding while maintaining transparency. They share a tightly folded structural template but there are striking differences among species. Their amino acid compositions are unusual. Even in mammals, -crystallins have high contents of sulfur-containing methionine and cysteine, but this reaches extremes in fish M-crystallins with up to 15% Met. In addition, fish M-crystallins do not conserve the paired tryptophan residues found in each domain in mammalian -crystallins and in the related -crystallins. To gain insight into important, evolutionarily conserved properties and functionality of -crystallins, zebrafish (Danio rerio) M2b and M7 were compared with mouse S and human D. For all four proteins, far UV CD spectra showed the expected -sheet secondary structure. Like the mammalian proteins, M7 was highly soluble but M2b was much less so. The heat and denaturant stability of both fish proteins was lower than either mammalian protein. The ability of full-length and truncated versions of human B-crystallin to retard aggregation of the heat denatured proteins also showed differences. However, when solution behavior was investigated by sedimentation velocity experiments, the diverse -crystallins showed remarkably similar hydrodynamic properties with low frictional ratios and partial specific volumes. The solution behavior of -crystallins, with highly compact structures suited for the densely packed environment of the lens, seems to be highly conserved and appears largely independent of amino acid composition.
C1 [Chen, Yingwei; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
[Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct Genom, NIH, Bg 6,Rm 106, Bethesda, MD 20892 USA.
EM graeme@helix.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU National Eye Institute; National Institute of Biomedical Imaging and
Bioengineering at the National Institutes of Health
FX Grant sponsor: Intramural Research Programs of the National Eye
Institute and the National Institute of Biomedical Imaging and
Bioengineering at the National Institutes of Health.
NR 51
TC 3
Z9 3
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD JAN
PY 2014
VL 23
IS 1
BP 76
EP 87
DI 10.1002/pro.2395
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 273WI
UT WOS:000328566600007
PM 24214907
ER
PT J
AU Zhao, HY
Chen, YW
Rezabkova, L
Wu, ZR
Wistow, G
Schuck, P
AF Zhao, Huaying
Chen, Yingwei
Rezabkova, Lenka
Wu, Zhengrong
Wistow, Graeme
Schuck, Peter
TI Solution properties of gamma-crystallins: Hydration of fish and mammal
gamma-crystallins
SO PROTEIN SCIENCE
LA English
DT Article
DE crystallin; protein hydration; protein hydrodynamics; hydrodynamic
modeling; protein interactions
ID ANGLE NEUTRON-SCATTERING; LIQUID PHASE-SEPARATION; X-RAY-ANALYSIS; EYE
LENS; S-CRYSTALLIN; PROTEIN INTERACTIONS; SEDIMENTATION; WATER;
TRANSPARENCY; CATARACT
AB Lens crystallins are found at the highest protein concentration of any tissue, ranging from 300 mg/mL in some mammals to over 1000 mg/mL in fish. Such high concentrations are necessary for the refraction of light, but impose extreme requirements for protein stability and solubility. -crystallins, small stable monomeric proteins, are particularly associated with the lowest hydration regions of the lens. Here, we examine the solvation of selected -crystallins from mammals (human D and mouse S) and fish (zebrafish M2b and M7). The thermodynamic water binding coefficient B-1 could be probed by sucrose expulsion, and the hydrodynamic hydration shell of tightly bound water was probed by translational diffusion and structure-based hydrodynamic boundary element modeling. While the amount of tightly bound water of human D was consistent with that of average proteins, the water binding of mouse S was found to be relatively low. M2b and M7 crystallins were found to exhibit extremely low degrees hydration, consistent with their role in the fish lens. M crystallins have a very high methionine content, in some species up to 15%. Structure-based modeling of hydration in M7 crystallin suggests low hydration is associated with the large number of surface methionine residues, likely in adaptation to the extremely high concentration and low hydration environment in fish lenses. Overall, the degree of hydration appears to balance stability and tissue density requirements required to produce and maintain the optical properties of the lens in different vertebrate species.
C1 [Zhao, Huaying; Rezabkova, Lenka; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA.
[Chen, Yingwei; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
[Wu, Zhengrong] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA.
RP Schuck, P (reprint author), NIH, Bldg 13,Rm 3N17,13 South Dr, Bethesda, MD 20892 USA.
EM schuckp@mail.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering; National
Eye Institute at the National Institutes of Health
FX Grant sponsor: Intramural Research Programs of the National Institute of
Biomedical Imaging and Bioengineering and the National Eye Institute at
the National Institutes of Health.
NR 74
TC 7
Z9 7
U1 2
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD JAN
PY 2014
VL 23
IS 1
BP 88
EP 99
DI 10.1002/pro.2394
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 273WI
UT WOS:000328566600008
PM 24282025
ER
PT S
AU Otto, M
AF Otto, Michael
BE Fey, PD
TI Staphylococcus epidermidis Pathogenesis
SO STAPHYLOCOCCUS EPIDERMIDIS: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Staphylococcus epidermidis; Pathogenesis; Phenol-soluble modulins;
Biofilm
ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COAGULASE-NEGATIVE STAPHYLOCOCCI;
PHENOL-SOLUBLE MODULINS; ACCUMULATION-ASSOCIATED PROTEIN;
CATHETER-ASSOCIATED INFECTION; BACTERIAL BIOFILM FORMATION; SEQUENCE
ELEMENT IS256; SURFACE PROTEIN; IN-VIVO; NASAL COLONIZATION
AB Staphylococcus epidermidis is the most frequently encountered member of the coagulase-negative staphylococci on human epithelial surfaces. It has emerged as an important nosocomial pathogen, especially in infections of indwelling medical devices. The mechanisms that S. epidermidis uses to survive during infection are in general of a passive nature, reflecting their possible origin in the commensal life of this bacterium. Most importantly, S. epidermidis excels in forming biofilms, sticky agglomerations that inhibit major host defense mechanisms. Furthermore, S. epidermidis produces a series of protective surface polymers and exoenzymes. Moreover, S. epidermidis has the capacity to secrete strongly cytolytic members of the phenol-soluble modulin (PSM) family, but PSMs in S. epidermidis overall appear to participate primarily in biofilm development. Finally, there is evidence for a virulence gene reservoir function of S. epidermidis, as it appears to have transferred important immune evasion and antibiotic resistance factors to Staphylococcus aureus. Conversely, S. epidermidis also has a beneficial role in balancing the microflora on human epithelial surfaces by controlling outgrowth of harmful bacteria such as in particular S. aureus. Recent research yielded detailed insight into key S. epidermidis virulence determinants and their regulation, in particular as far as biofilm formation is concerned, but we still have a serious lack of understanding of the in vivo relevance of many pathogenesis mechanisms and the factors that govern the commensal life of S. epidermidis
C1 NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
OI Otto, Michael/0000-0002-2222-4115
FU Intramural NIH HHS
NR 104
TC 11
Z9 11
U1 4
U2 20
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-62703-736-5; 978-1-62703-735-8
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1106
BP 17
EP 31
DI 10.1007/978-1-62703-736-5_2
D2 10.1007/978-1-62703-736-5
PG 15
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA BJH42
UT WOS:000328216100003
PM 24222452
ER
PT S
AU Joo, HS
Otto, M
AF Joo, Hwang-Soo
Otto, Michael
BE Fey, PD
TI The Isolation and Analysis of Phenol-Soluble Modulins of Staphylococcus
epidermidis
SO STAPHYLOCOCCUS EPIDERMIDIS: METHODS AND PROTOCOLS
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Staphylococcus epidermidis; Phenol-soluble modulins; Peptide toxin;
Liquid chromatography; Mass spectrometry
ID PEPTIDES; EXPRESSION; PATHOGEN; BIOFILMS
AB Phenol-soluble modulins (PSMs) are multifunctional peptide toxins produced by many staphylococcal strains. PSMs have received much recent attention, owing to multiple reports underscoring their importance for staphylococcal pathogenesis. Members of the PSM family may be strongly cytolytic to neutrophils and other cell types; promote inflammatory, receptor-mediated responses in several human cell types; and contribute to biofilm structuring and detachment. Here we describe biochemical methods to isolate, purify, and quantitatively analyze Staphylococcus epidermidis PSMs.
C1 [Joo, Hwang-Soo; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Joo, HS (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
OI JOO, HWANG-SOO/0000-0003-4668-3225; Otto, Michael/0000-0002-2222-4115
FU Intramural NIH HHS
NR 17
TC 12
Z9 12
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 978-1-62703-736-5; 978-1-62703-735-8
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1106
BP 93
EP 100
DI 10.1007/978-1-62703-736-5_7
D2 10.1007/978-1-62703-736-5
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA BJH42
UT WOS:000328216100008
PM 24222457
ER
PT J
AU Lanza, GM
Moonen, C
Baker, JR
Chang, E
Cheng, Z
Grodzinski, P
Ferrara, K
Hynynen, K
Kelloff, G
Lee, YEK
Patri, AK
Sept, D
Schnitzer, JE
Wood, BJ
Zhang, MQ
Zheng, G
Farahani, K
AF Lanza, Gregory M.
Moonen, Chrit
Baker, James R., Jr.
Chang, Esther
Cheng, Zheng
Grodzinski, Piotr
Ferrara, Katherine
Hynynen, Kullervo
Kelloff, Gary
Lee, Yong-Eun Koo
Patri, Anil K.
Sept, David
Schnitzer, Jan E.
Wood, Bradford J.
Zhang, Miqin
Zheng, Gang
Farahani, Keyvan
TI Assessing the barriers to image-guided drug delivery
SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
LA English
DT Review
ID MAMMALIAN CEREBRAL EPITHELIUM; CHRONIC LYMPHOCYTIC-LEUKEMIA;
LOW-DENSITY-LIPOPROTEIN; THERANOSTIC NANOPARTICLES; IN-VIVO; LEUKOCYTE
TRANSMIGRATION; MAGNETIC-RESONANCE; FOCUSED ULTRASOUND;
ENDOTHELIAL-CELLS; THERMOSENSITIVE LIPOSOMES
AB Imaging has become a cornerstone for medical diagnosis and the guidance of patient management. A new field called image-guided drug delivery (IGDD) now combines the vast potential of the radiological sciences with the delivery of treatment and promises to fulfill the vision of personalized medicine. Whether imaging is used to deliver focused energy to drug-laden particles for enhanced, local drug release around tumors, or it is invoked in the context of nanoparticle-based agents to quantify distinctive biomarkers that could risk stratify patients for improved targeted drug delivery efficiency, the overarching goal of IGDD is to use imaging to maximize effective therapy in diseased tissues and to minimize systemic drug exposure in order to reduce toxicities. Over the last several years, innumerable reports and reviews covering the gamut of IGDD technologies have been published, but inadequate attention has been directed toward identifying and addressing the barriers limiting clinical translation. In this consensus opinion, the opportunities and challenges impacting the clinical realization of IGDD-based personalized medicine were discussed as a panel and recommendations were proffered to accelerate the field forward. WIREs Nanomed Nanobiotechnol 2014, 6:1-14. doi: 10.1002/wnan.1247 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.
C1 [Lanza, Gregory M.] Washington Univ, Sch Med, Div Cardiol, St Louis, MO USA.
[Moonen, Chrit] UMC Utrecht, Image Sci Inst, Utrecht, Netherlands.
[Baker, James R., Jr.; Lee, Yong-Eun Koo; Sept, David] Univ Michigan, Div Clin Immunol & Allergy, Ann Arbor, MI 48109 USA.
[Chang, Esther] Georgetown Univ, Dept Oncol, Washington, DC USA.
[Cheng, Zheng] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
[Grodzinski, Piotr; Kelloff, Gary; Farahani, Keyvan] NCI, Bethesda, MD 20892 USA.
[Ferrara, Katherine] Univ Calif Davis, Dept Bioengn, Davis, CA 95616 USA.
[Hynynen, Kullervo] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Patri, Anil K.] Natl Canc Inst Fredrick, Nanotechnol Characterizat Lab, Frederick, MD USA.
[Schnitzer, Jan E.] Proteogen Res Inst Syst Med, San Diego, CA USA.
[Wood, Bradford J.] NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA.
[Zhang, Miqin] Univ Washington, Dept Mat Sci & Engn, Seattle, WA 98195 USA.
[Zheng, Gang] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
RP Farahani, K (reprint author), NCI, Bethesda, MD 20892 USA.
EM farahank@mail.nih.gov
RI Cheng, Zhen/K-2843-2012; Nanotechnology Characterization Lab,
NCL/K-8454-2012; Zhang, Miqin/F-5537-2010; Moonen, Chrit/K-4434-2016;
OI Zhang, Miqin/0000-0001-8974-1494; Moonen, Chrit/0000-0001-5593-3121;
Sept, David/0000-0003-3719-2483; Ferrara, Katherine/0000-0002-4976-9107
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA093373, R01
CA154737, U54 CA136398]; NHLBI NIH HHS [R42 HL112518]; NIAMS NIH HHS
[R01 AR056468]; NINDS NIH HHS [U01 NS073457]
NR 154
TC 14
Z9 14
U1 3
U2 48
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5116
EI 1939-0041
J9 WIRES NANOMED NANOBI
JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol.
PD JAN
PY 2014
VL 6
IS 1
BP 1
EP 14
DI 10.1002/wnan.1247
PG 14
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 270YA
UT WOS:000328354300001
PM 24339356
ER
PT J
AU Ha, NH
Hunter, KW
AF Ha, Ngoc-Han
Hunter, Kent W.
TI Using a systems biology approach to understand and study the mechanisms
of metastasis
SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE
LA English
DT Article
ID BREAST-CANCER METASTASIS; MALIGNANT-TUMOR; LUNG-CANCER; STEM-CELLS;
E-CADHERIN; MICRORNA; PROGRESSION; PROFILES; MELANOMA; SUSCEPTIBILITY
AB Metastasis remains the main cause for cancer-related deaths due to the lack of effective therapy. The clonal selection model has long been thought to be the primary mechanism of metastatic progression but many different mechanisms have been hypothesized for the progression from tumorigenesis to the successful dissemination and expansion of tumor cells at the secondary site. MicroRNAs, germline polymorphisms in combination with the tumor microenvironment are few of the different pathways to explain the metastatic cascade. Technological advances for high-throughput screening of cells such as expression profiling, next generation sequencing, as well as global network analyses have advanced the studies of these mechanisms. Combined with new insights into the various mechanisms of metastasis a systems biology approach has also been shown to be useful in identifying metastasis-specific gene signatures as well as predicting disease outcome. Furthermore, the results of these studies have been relevant for identifying biomarkers for metastatic disease. (C) 2013 Wiley Periodicals, Inc.
C1 [Ha, Ngoc-Han; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Hunter, KW (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
EM hunterk@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 44
TC 0
Z9 0
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5094
EI 1939-005X
J9 WIRES SYST BIOL MED
JI Wiley Interdiscip. Rev.-Syst. Biol
PD JAN
PY 2014
VL 6
IS 1
BP 107
EP 114
DI 10.1002/wsbm.1237
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 273TF
UT WOS:000328558500007
PM 23873855
ER
PT J
AU Deshpande, N
Metter, JE
Guralnik, J
Bandinelli, S
Ferrucci, L
AF Deshpande, Nandini
Metter, Jeffrey E.
Guralnik, Jack
Bandinelli, Stefania
Ferrucci, Luigi
TI Sensorimotor and psychosocial determinants of 3-year incident mobility
disability in middle-aged and older adults
SO AGE AND AGEING
LA English
DT Article
DE mobility; disability; depression; vision; muscle strength; older people
ID CONTRAST SENSITIVITY; WOMENS HEALTH; PREDICTORS; STRENGTH; PERFORMANCE;
DIFFICULTY; INCHIANTI; DECLINE; CHART
AB Objective: to identify sensorimotor and psychosocial determinants of 3-year incident mobility disability.
Design: prospective.
Setting: population-based sample of community-dwelling older persons.
Participants: community-living middle-aged and older persons (age: 50-85 years) without baseline mobility disability (n = 622).
Measurements: mobility disability, defined as self-reported inability to walk a quarter mile without resting or inability to walk up a flight of stairs unsupported, was ascertained at baseline and 3-year follow-up. Potential baseline determinant characteristics included demographics, education, social support, financial condition, knee extensor strength, visual contrast sensitivity, cognition, depression, presence of chronic conditions and history of falls.
Results: a total of 13.5% participant reported 3-year incident mobility disability. Age >= 75 years, female sex, knee extensor strength in the lowest quartile, visual contrast sensitivity < 1.7 on the Pelli-Robson chart or significant depressive symptoms (CESD score > 16) were independent determinants of 3-year incident mobility disability (ORs 1.84-16.51).
Conclusions: low visual contrast sensitivity, poor knee extensor strength and significant depressive symptoms are independent determinants of future onset of mobility disability.
C1 [Deshpande, Nandini] Queens Univ, Sch Rehabil Therapy, Kingston, ON, Canada.
[Metter, Jeffrey E.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Guralnik, Jack] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
RP Deshpande, N (reprint author), Queens Univ, Sch Rehabil Therapy, Kingston, ON, Canada.
EM nandinijd@yahoo.com
FU Italian Ministry of Health [ICS 110.1\RS97.71]; National Institute on
Aging [N01-AG-916413, N01-AG-821336, N01-AG-5-0002]; NIA [R01 AG027012];
Intramural Research Program, National Institute on Aging, NIH
FX The InCHIANTI study was supported as a 'targeted project' (ICS
110.1\RS97.71) by the Italian Ministry of Health and in part, by
National Institute on Aging Contracts N01-AG-916413, N01-AG-821336,
N01-AG-5-0002 and NIA Grant R01 AG027012 and the Intramural Research
Program, National Institute on Aging, NIH.
NR 29
TC 2
Z9 2
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD JAN
PY 2014
VL 43
IS 1
BP 64
EP 69
DI 10.1093/ageing/aft135
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 271JZ
UT WOS:000328389200013
PM 24042004
ER
PT J
AU Fisher, D
Li, CM
Chiu, MS
Themann, CL
Petersen, H
Jonasson, F
Jonsson, PV
Sverrisdottir, JE
Garcia, M
Harris, TB
Launer, LJ
Eiriksdottir, G
Gudnason, V
Hoffman, HJ
Cotch, MF
AF Fisher, Diana
Li, Chuan-Ming
Chiu, May S.
Themann, Christa L.
Petersen, Hannes
Jonasson, Frithbert
Jonsson, Palmi V.
Sverrisdottir, Johanna Eyrun
Garcia, Melissa
Harris, Tamara B.
Launer, Lenore J.
Eiriksdottir, Gudny
Gudnason, Vilmundur
Hoffman, Howard J.
Cotch, Mary Frances
TI Impairments in hearing and vision impact on mortality in older people:
the AGES-Reykjavik Study
SO AGE AND AGEING
LA English
DT Article
DE AGES-Reykjavik study; hearing; vision; dual sensory impairment;
all-cause mortality; cardiovascular disease mortality; older people
ID HEALTH INTERVIEW SURVEY; VISUAL IMPAIRMENT; SENSORY IMPAIRMENT;
FOLLOW-UP; POPULATION; DISABILITY; CATARACT; PROJECT; ACUITY; ADULTS
AB Objective: to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people.
Design: population-based cohort study.
Participants: the study population included 4,926 Icelandic individuals, aged >= 67 years, 43.4% male, who completed vision and hearing examinations between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) and were followed prospectively for mortality through 2009.
Methods: participants were classified as having 'moderate or greater' degree of impairment for vision only (VI), hearing only (HI), and both vision and hearing (dual sensory impairment, DSI). Cox proportional hazard regression, with age as the time scale, was used to calculate hazard ratios (HR) associated with impairment and mortality due to all-causes and specifically CVD after a median follow-up of 5.3 years.
Results: the prevalence of HI, VI and DSI were 25.4, 9.2 and 7.0%, respectively. After adjusting for age, significantly (P < 0.01) increased mortality from all causes, and CVD was observed for HI and DSI, especially among men. After further adjustment for established mortality risk factors, people with HI remained at higher risk for CVD mortality [HR: 1.70 (1.27-2.27)], whereas people with DSI remained at higher risk of all-cause mortality [HR: 1.43 (1.11-1.85)] and CVD mortality [HR: 1.78 (1.18-2.69)]. Mortality rates were significantly higher in men with HI and DSI and were elevated, although not significantly, among women with HI.
Conclusions: older men with HI or DSI had a greater risk of dying from any cause and particularly cardiovascular causes within a median 5-year follow-up. Women with hearing impairment had a non-significantly elevated risk. Vision impairment alone was not associated with increased mortality.
C1 [Fisher, Diana; Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Li, Chuan-Ming; Chiu, May S.; Hoffman, Howard J.] NIDCD, Div Sci Programs, Epidemiol & Stat Program, NIH, Bethesda, MD USA.
[Themann, Christa L.] NIOSH, Hearing Loss Prevent Team, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
[Petersen, Hannes; Jonasson, Frithbert; Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Petersen, Hannes] Landspitali Univ Hosp, Dept Otolaryngol Head & Neck Surg, Reykjavik, Iceland.
[Jonasson, Frithbert] Landspitali Univ Hosp, Reykjavik, Iceland.
[Jonsson, Palmi V.] Landspitali Univ Hosp, Dept Geriatr, IS-101 Reykjavjk, Iceland.
[Sverrisdottir, Johanna Eyrun; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Garcia, Melissa; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Fisher, D (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
EM diana.fisher@nih.gov
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary
Frances/0000-0002-2046-4350
FU National Institutes of Health, National Institute on Aging (NIA)
[N01-AG-12100]; NIA [Z01-AG007380]; National Eye Institute (NEI)
[ZIAEY000401]; National Institute on Deafness and Other Communication
Disorders (NIDCD) Division of Scientific Programs [IAA Y2-DC-1004-02];
Hjartavernd (Icelandic Heart Association); Althingi (Icelandic
Parliament)
FX This work was supported by the National Institutes of Health, National
Institute on Aging (NIA) (contract number N01-AG-12100); the NIA
Intramural Research Program (Z01-AG007380); the National Eye Institute
(NEI) Intramural Research Program (ZIAEY000401); the National Institute
on Deafness and Other Communication Disorders (NIDCD) Division of
Scientific Programs (IAA Y2-DC-1004-02); and with funding from
Hjartavernd (Icelandic Heart Association) and the Althingi (Icelandic
Parliament).
NR 30
TC 25
Z9 26
U1 3
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
EI 1468-2834
J9 AGE AGEING
JI Age Ageing
PD JAN
PY 2014
VL 43
IS 1
BP 69
EP 76
DI 10.1093/ageing/aft122
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 271JZ
UT WOS:000328389200014
PM 23996030
ER
PT J
AU Schuemie, MJ
Ryan, PB
Suchard, MA
Shahn, Z
Madigan, D
AF Schuemie, Martijn J.
Ryan, Patrick B.
Suchard, Marc A.
Shahn, Zach
Madigan, David
TI Discussion: An estimate of the science-wise false discovery rate and
application to the top medical literature
SO BIOSTATISTICS
LA English
DT Editorial Material
ID CASE SERIES
C1 [Schuemie, Martijn J.; Ryan, Patrick B.; Suchard, Marc A.; Shahn, Zach; Madigan, David] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD 20814 USA.
[Schuemie, Martijn J.; Ryan, Patrick B.] Janssen Res & Dev LLC, Titusville, NJ 08560 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
[Shahn, Zach; Madigan, David] Columbia Univ, Dept Stat, New York, NY 10027 USA.
RP Schuemie, MJ (reprint author), Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD 20814 USA.
EM mschuemi@its.jnj.com
NR 4
TC 3
Z9 3
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2014
VL 15
IS 1
BP 36
EP 39
DI 10.1093/biostatistics/kxt037
PG 5
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 270AG
UT WOS:000328286700007
PM 24068252
ER
PT J
AU Finak, G
McDavid, A
Chattopadhyay, P
Dominguez, M
de Rosa, S
Roederer, M
Gottardo, R
AF Finak, Greg
McDavid, Andrew
Chattopadhyay, Pratip
Dominguez, Maria
de Rosa, Steve
Roederer, Mario
Gottardo, Raphael
TI Mixture models for single-cell assays with applications to vaccine
studies
SO BIOSTATISTICS
LA English
DT Article
DE Bayesian modeling; Expectation-Maximization; Flow cytometry;
Hierarchical modeling; Immunology; Marginal likelihood; Markov Chain
Monte Carlo; MIMOSA; Single-cell gene expression
ID DIFFERENTIAL GENE-EXPRESSION; T-CELLS; RESPONSES; VIRUS
AB Blood and tissue are composed of many functionally distinct cell subsets. In immunological studies, these can be measured accurately only using single-cell assays. The characterization of these small cell subsets is crucial to decipher system-level biological changes. For this reason, an increasing number of studies rely on assays that provide single-cell measurements of multiple genes and proteins from bulk cell samples. A common problem in the analysis of such data is to identify biomarkers (or combinations of biomarkers) that are differentially expressed between two biological conditions (e. g. before/after stimulation), where expression is defined as the proportion of cells expressing that biomarker (or biomarker combination) in the cell subset(s) of interest. Here, we present a Bayesian hierarchical framework based on a beta-binomial mixture model for testing for differential biomarker expression using single-cell assays. Our model allows the inference to be subject specific, as is typically required when assessing vaccine responses, while borrowing strength across subjects through common prior distributions. We propose two approaches for parameter estimation: an empirical-Bayes approach using an Expectation-Maximization algorithm and a fully Bayesian one based on a Markov chain Monte Carlo algorithm. We compare our method against classical approaches for single-cell assays including Fisher's exact test, a likelihood ratio test, and basic log-fold changes. Using several experimental assays measuring proteins or genes at single-cell level and simulations, we show that our method has higher sensitivity and specificity than alternative methods. Additional simulations show that our framework is also robust to model misspecification. Finally, we demonstrate how our approach can be extended to testing multivariate differential expression across multiple biomarker combinations using a Dirichlet-multinomial model and illustrate this approach using single-cell gene expression data and simulations.
C1 [Finak, Greg; McDavid, Andrew; de Rosa, Steve; Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Chattopadhyay, Pratip; Dominguez, Maria; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[de Rosa, Steve] Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Seattle, WA 98109 USA.
RP Finak, G (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
EM gfinak@fhcrc.org
OI Finak, Greg/0000-0003-4341-9090; McDavid, Andrew/0000-0002-6581-1213;
Chattopadhyay, Pratip/0000-0002-5457-9666
FU National Institute of Allergy and Infectious Diseases (NIAID); National
Institutes of Health (NIH) [R01 EB008400, U01 AI068635-01]; Bill and
Melinda Gates Foundation [OPP38744, OPP1032317]; Collaboration for AIDS
Vaccine Discovery (CAVD) [OPP1032325]; NIAID; NIH [UM1AI068618]; Public
Health Service; University of Washington Center for AIDS Research [UM1
AI068618, P30 AI027757]; NIAID [U19AI089986]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID) and the
National Institutes of Health (NIH) grants [R01 EB008400, U01
AI068635-01], the Bill and Melinda Gates Foundation through grants to
the Vaccine and Immunology Statistical Center (VISC) [OPP38744,
OPP1032317], and the Collaboration for AIDS Vaccine Discovery (CAVD)
[OPP1032325]. HVTN065 was conducted by the HIV Vaccine Trials Network
(HVTN) and supported by NIAID. The HVTN Lab Program is supported by the
NIH [UM1AI068618], the Public Health Service, and the University of
Washington Center for AIDS Research [UM1 AI068618, P30 AI027757]. This
work was performed as a project of the Human Immune Phenotyping
Consortium (HIPC) and funded by the NIAID [U19AI089986].
NR 25
TC 13
Z9 13
U1 2
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2014
VL 15
IS 1
BP 87
EP 101
DI 10.1093/biostatistics/kxt024
PG 15
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 270AG
UT WOS:000328286700012
PM 23887981
ER
PT J
AU Baron, BW
Anastasi, J
Bies, J
Reddy, PL
Joseph, L
Thirman, MJ
Wroblewski, K
Wolff, L
Baron, JM
AF Baron, Beverly W.
Anastasi, John
Bies, Juraj
Reddy, Poluru L.
Joseph, Loren
Thirman, Michael J.
Wroblewski, Kristen
Wolff, Linda
Baron, Joseph M.
TI GFI1B, EVI5, MYB-Additional genes that cooperate with the human BCL6
gene to promote the development of lymphomas
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE BCL6 transgenic mice; Cooperating genes; Lymphoma development; GFI1B;
EVI5; MYB
ID B-CELL LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYB; PROVIRAL
INTEGRATIONS; MYELOID-LEUKEMIA; UP-REGULATION; ACTIVATION; EXPRESSION;
ONCOGENE; DIFFERENTIATION
AB The BCL6 gene, which is expressed in certain B- and T-cell human lymphomas, is involved with chromosomal rearrangements and mutations in a number of these neoplasms. Lymphomagenesis is believed to evolve through a multi-step accumulation of genetic alterations in these tumors. We used retroviral insertional mutagenesis in transgenic mice expressing the human BCL6 transgene in order to identify genes that cooperate with BCL6 during lymphomatous transformation. We previously reported PIM1 as the most frequently recurring cooperating gene in this model. We now report three newly identified cooperating genes-GFI1B, EVI5, and MYB-that we identified in the lymphomas of retroviral-injected BCL6 transgenic mice (but not in retroviral-injected non-transgenic controls); mRNA and protein expression of GFI1B and EVI5 were decreased in the murine tumors, whereas MYB mRNA and protein expression were increased or decreased. These findings correlated with protein expression in human lymphomas, both B- and T-cell. Improved therapy of lymphomas may necessitate the development of combinations of drugs that target the alterations specific to each neoplasm. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Baron, Beverly W.; Anastasi, John; Reddy, Poluru L.; Joseph, Loren] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Bies, Juraj; Wolff, Linda] NCI, Leukemogenesis Sect, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Thirman, Michael J.; Baron, Joseph M.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Wroblewski, Kristen] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
RP Baron, BW (reprint author), Univ Chicago, CCD, Room 2600F,MC8049,5720 S Drexel Ave, Chicago, IL 60637 USA.
EM beverly.baron@uchospitals.edu
FU Department of Pathology at The University of Chicago; University of
Chicago Cancer Center Support Grant [P30 CA014599]; Hematology Research
Funds at The University of Chicago
FX We thank Dr. B. Gladstone for technical assistance, Dr. I. Aifantis for
antibodies for flow cytometry, D. Lane for expertise in
immunohistochemistry, and R. Duggan for assistance with FACS. This work
was supported by the Department of Pathology at The University of
Chicago (to BWB), University of Chicago Cancer Center Support Grant P30
CA014599 (to BWB), and Hematology Research Funds at The University of
Chicago donated by S. Samsky and E. Lanzl (to JMB).
NR 49
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1079-9796
EI 1096-0961
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD JAN
PY 2014
VL 52
IS 1
BP 68
EP 75
DI 10.1016/j.bcmd.2013.07.003
PG 8
WC Hematology
SC Hematology
GA 265AP
UT WOS:000327922400014
PM 23910958
ER
PT J
AU Jolly, C
Winfree, S
Hansen, B
Steele-Mortimer, O
AF Jolly, Carrie
Winfree, Seth
Hansen, Bryan
Steele-Mortimer, Olivia
TI The Annexin A2/p11 complex is required for efficient invasion of
Salmonella Typhimurium in epithelial cells
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; EFFECTOR PROTEIN SOPB; HOST-CELL;
ACTIN DYNAMICS; INOSITOL PHOSPHATASE; BACTERIAL INVASION; AKT
ACTIVATION; IMAGE-ANALYSIS; AHNAK PROTEIN; CANCER-CELLS
AB The facultative intracellular pathogen, Salmonella enterica, triggers its own uptake into non-phagocytic epithelial cells. Invasion is dependent on a type 3 secretion system (T3SS), which delivers a cohort of effector proteins across the plasma membrane where they induce dynamic actin-driven ruffling of the membrane and ultimately, internalization of the bacteria into a modified phagosome. In eukaryotic cells, the calcium- and phospholipid-binding protein Annexin A2 (AnxA2) functions as a platform for actin remodelling in the vicinity of dynamic cellular membranes. AnxA2 is mostly found in a stable heterotetramer, with p11, which can interact with other proteins such as the giant phosphoprotein AHNAK. We show here that AnxA2, p11 and AHNAK are required for T3SS-mediated Salmonella invasion of cultured epithelial cells and that the T3SS effector SopB is required for recruitment of AnxA2 and AHNAK to Salmonella invasion sites. Altogether this work shows that, in addition to targeting Rho-family GTPases, Salmonella can intersect the host cell actin pathway via AnxA2.
C1 [Jolly, Carrie; Winfree, Seth; Steele-Mortimer, Olivia] NIAID, Salmonella Host Cell Interact Sect, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
[Hansen, Bryan] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Steele-Mortimer, O (reprint author), NIAID, Salmonella Host Cell Interact Sect, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
EM omortimer@niaid.nih.gov
FU NIH, NIAID
FX We are grateful to members of the Steele-Mortimer lab for their helpful
discussions and encouragement and particularly to Tregei Starr for
expert assistance with figures. We thank Ken Fields and Volker Gerker
for providing antibodies and Yun Soo Bae for providing MEFs. This
research was supported by the Intramural Research Program of the NIH,
NIAID. The authors declare no conflict of interest.
NR 61
TC 11
Z9 11
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
EI 1462-5822
J9 CELL MICROBIOL
JI Cell Microbiol.
PD JAN
PY 2014
VL 16
IS 1
BP 64
EP 77
DI 10.1111/cmi.12180
PG 14
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 268ZJ
UT WOS:000328209100006
PM 23931152
ER
PT J
AU Tageja, N
Manasanch, EE
Korde, N
Kwok, M
Mailankody, S
Bhutani, M
Roschewski, M
Landgren, O
AF Tageja, Nishant
Manasanch, Elisabet E.
Korde, Neha
Kwok, Mary
Mailankody, Sham
Bhutani, Manisha
Roschewski, Mark
Landgren, Ola
TI Smoldering multiple myeloma: present position and potential promises
SO EUROPEAN JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE smoldering myeloma; multiple myeloma; plasma cell dyscrasia;
lenalidomide; carfilzomib; flow cytometry
ID UNDETERMINED SIGNIFICANCE MGUS; MULTIPARAMETER FLOW-CYTOMETRY; STEM-CELL
TRANSPLANTATION; MARROW PLASMA-CELLS; TOLL-LIKE RECEPTORS; WHOLE-BODY
MRI; MONOCLONAL GAMMOPATHY; BONE-MARROW; HIGH-RISK; UNKNOWN SIGNIFICANCE
AB Since smoldering multiple myeloma (SMM) was first described over three decades ago based on a case series of six patients, its definition and our understanding of the entity have evolved considerably. The risk of progression to symptomatic myeloma (MM) varies greatly among individuals diagnosed with myeloma precursor disease. Epidemiologic, molecular, flow cytometric and radiological techniques have demonstrated that this transformation to MM from precursor states is not sudden but rather a continuous overlapping series of events with evidence of end-organ damage that could manifest in the earliest stages of disease. Contemporary antimyeloma therapies can yield rapid, deep, and durable responses with manageable toxicities, and molecular-cell-based measures are now available to rule out minimal residual disease. With this information, clinical studies with correlative measures can now be developed to test the fundamental hypothesis that intervention in early myeloma may provide a measurable clinical benefit to patients by either delaying progression or eradicating plasma cell clones.
C1 [Tageja, Nishant; Manasanch, Elisabet E.; Korde, Neha; Kwok, Mary; Mailankody, Sham; Bhutani, Manisha; Roschewski, Mark; Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10-Rm 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute of the
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute of the National Institutes of Health.
NR 79
TC 3
Z9 3
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0902-4441
EI 1600-0609
J9 EUR J HAEMATOL
JI Eur. J. Haematol.
PD JAN
PY 2014
VL 92
IS 1
BP 1
EP 12
DI 10.1111/ejh.12205
PG 12
WC Hematology
SC Hematology
GA 268ZI
UT WOS:000328209000001
PM 24112232
ER
PT J
AU Barrington, DS
Adeyemo, AA
Rotimi, CN
AF Barrington, Debbie S.
Adeyemo, Adebowale A.
Rotimi, Charles N.
TI Childhood Family Living Arrangements and Blood Pressure in Black Men The
Howard University Family Study
SO HYPERTENSION
LA English
DT Article
DE African continental ancestry group; blood pressure; family
characteristics; hypertension; social environment
ID SOCIOECONOMIC POSITION; LIFE-COURSE; CARDIOVASCULAR-DISEASE; EARLY
ADULTHOOD; BIRTH-WEIGHT; SOCIAL-CLASS; HYPERTENSION; ASSOCIATION;
MORTALITY; HEART
AB Black men have higher blood pressure (BP) levels and consequently higher prevalence of hypertension compared with men from other ethnic groups in the United States. Socio-familial factors in childhood have been found to play an important role in hypertension, but few studies have examined this relationship among black men. We investigated whether childhood family living arrangements are independently associated with mean BP and hypertension in a cross-sectional sample of 515 unrelated black male participants aged 20 years enrolled in the Howard University Family Study between 2001 and 2008. Black men who lived with both parents compared with the reference group of men who never lived with both parents during their lifetime had lower systolic BP (-4.4 mm Hg [95% confidence interval {CI}, -7.84 to -0.96]), pulse pressure (-3.9 mm Hg [95% CI, -6.28 to -1.51]), and mean arterial BP (-2.0 mm Hg [95% CI, -4.44 to 0.51]). This protective effect was more pronounced among men who lived with both parents for 1 to 12 years of their lives; they had decreased systolic BP (-6.5 mm Hg [95% CI, -10.99 to -1.95]), pulse pressure (-5.4 mm Hg [95% CI, -8.48 to -2.28]), mean arterial pressure (-3.3 mm Hg [95% CI, -6.56 to 0.00]), and a 46% decreased odds of developing hypertension (odds ratio=0.54; 95% CI, 0.30 to 0.99). No statistically significant associations were found for diastolic BP. These results provide preliminary evidence that childhood family structure exerts a long-term influence on BP among black men.
C1 [Barrington, Debbie S.] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD 20892 USA.
[Barrington, Debbie S.; Adeyemo, Adebowale A.; Rotimi, Charles N.] NHGRI, NIH, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA.
RP Barrington, DS (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, 3 Ctr Dr,Bldg 3,Rm 5W13,MSC 0311, Bethesda, MD 20892 USA.
EM debbie.barrington@nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU National Institute on Minority Health and Health Disparities (National
Institutes of Health [NIH]) [K22MD006133]; NIH [S06GM008016-320107,
S06GM008016-380111, 2M01RR010284]; NIH Intramural Research Program in
the Center for Research on Genomics and Global Health [Z01HG200362]
FX This study was supported by the National Institute on Minority Health
and Health Disparities (National Institutes of Health [NIH]) grant
K22MD006133 (D.S. Barrington). The Howard University Family Study was
supported by NIH grants S06GM008016-320107 (C.N. Rotimi),
S06GM008016-380111 (A.A. Adeyemo), and 2M01RR010284. This research was
also supported, in part, by the NIH Intramural Research Program in the
Center for Research on Genomics and Global Health (Z01HG200362). The
contents of this publication are solely the responsibility of the
authors and do not necessarily represent the official view of the NIH.
NR 40
TC 3
Z9 3
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JAN
PY 2014
VL 63
IS 1
BP 48
EP 53
DI 10.1161/HYPERTENSIONAHA.113.01629
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 268YM
UT WOS:000328206800015
PM 24296284
ER
PT J
AU Xia, Y
Yang, XR
Fu, ZZ
Paudel, O
Abramowitz, J
Birnbaumer, L
Sham, JSK
AF Xia, Yang
Yang, Xiao-Ru
Fu, Zhenzhen
Paudel, Omkar
Abramowitz, Joel
Birnbaumer, Lutz
Sham, James S. K.
TI Classical Transient Receptor Potential 1 and 6 Contribute to Hypoxic
Pulmonary Hypertension Through Differential Regulation of Pulmonary
Vascular Functions
SO HYPERTENSION
LA English
DT Article
DE hypertension; pulmonary; hypoxia; TRPC1 channel; TRPC6 channel; vascular
smooth muscle
ID ARTERIAL SMOOTH-MUSCLE; INDUCED UP-REGULATION; MYOGENIC TONE; CA2+
ENTRY; EXPRESSION; CHANNELS; VASOCONSTRICTION; CELLS; RATS; MECHANISM
AB Hypoxic pulmonary hypertension is characterized by increased vascular tone, altered vasoreactivity, and vascular remodeling, which are associated with alterations in Ca2+ homeostasis in pulmonary arterial smooth muscle cells. We have previously shown that classical transient receptor potential 1 and 6 (TRPC1 and TRPC6) are upregulated in pulmonary arteries (PAs) of chronic hypoxic rats, but it is unclear whether these channels are essential for the development of pulmonary hypertension. Here we found that pulmonary hypertension was suppressed in TRPC1 and TRPC6 knockout (Trpc1(-/-) and Trpc6(-/-)) mice compared with wild-type after exposure to 10% O-2 for 1 and 3 weeks. Muscularization of pulmonary microvessels was inhibited, but rarefaction was unaltered in hypoxic Trpc1(-/-) and Trpc6(-/-) mice. Small PAs of normoxic wild-type mice exhibited vasomotor tone, which was significantly enhanced by chronic hypoxia. Similar vasomotor tone was found in normoxic Trpc1(-/-) PAs, but the hypoxia-induced enhancement was blunted. In contrast, there was minimal vascular tone in normoxic Trpc6(-/-) PAs, but the hypoxia-enhanced tone was preserved. Chronic hypoxia caused significant increase in serotonin-induced vasoconstriction; the augmented vasoreactivity was attenuated in Trpc1(-/-) and eliminated in Trpc6(-/-) PAs. Moreover, the effects of 3-week hypoxia on pulmonary arterial pressure, right ventricular hypertrophy, and muscularization of microvessels were further suppressed in TRPC1-TRPC6 double-knockout mice. Our results, therefore, provide clear evidence that TRPC1 and TRPC6 participate differentially in various pathophysiological processes, and that the presence of TRPC1 and TRPC6 is essential for the full development of hypoxic pulmonary hypertension in the mouse model.
C1 [Xia, Yang; Yang, Xiao-Ru; Fu, Zhenzhen; Paudel, Omkar; Sham, James S. K.] Johns Hopkins Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Xia, Yang] Southern Med Univ, Nanfang Hosp, Dept Resp & Crit Care Med, Chron Airways Dis Lab, Guangzhou, Guangdong, Peoples R China.
[Abramowitz, Joel; Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Durham, NC USA.
RP Sham, JSK (reprint author), Johns Hopkins Asthma & Allergy Ctr, Div Pulm & Crit Care Med, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA.
EM jsks@jhmi.edu
RI Abramowitz, Joel/A-2620-2015
FU National Institutes of Health (NIH) [R01 HL071835, R01 HL075134]; NIH,
National Institute of Environmental Health Sciences [Z01-ES-101684]
FX This work was supported by National Institutes of Health (NIH) grants
(R01 HL071835 and R01 HL075134 to J.S.K.S.) and by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences (Project Z01-ES-101684 to L.B.).
NR 29
TC 16
Z9 19
U1 2
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JAN
PY 2014
VL 63
IS 1
BP 173
EP 180
DI 10.1161/HYPERTENSIONAHA.113.01902
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 268YM
UT WOS:000328206800032
PM 24144647
ER
PT J
AU Vaz, JS
Kac, G
Nardi, AE
Hibbeln, JR
AF Vaz, Juliana S.
Kac, Gilberto
Nardi, Antonio E.
Hibbeln, Joseph R.
TI Omega-6 fatty acids and greater likelihood of suicide risk and major
depression in early pregnancy
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Pregnancy; Suicide risk; Major depressive disorder; Arachidonic acid;
Omega-6 fatty acids
ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND;
PERINATAL DEPRESSION; ARACHIDONIC-ACID; LINOLEIC-ACID;
OMEGA-3-FATTY-ACIDS; BIOMARKERS; DISORDER; PHOSPHOLIPASE-A2
AB Objective: To estimate the prevalence of suicide risk (SR) and major depressive episodes (MDEs) in early pregnancy, as well as the relationship of serum fatty acid status to these outcomes.
Methods: Cross-sectional analyses were performed on data from 234 pregnant women enrolled in a prospective cohort study in Rio de Janeiro, Brazil. SR and MDE were defined according to the Mini International Neuropsychiatric Interview. Fatty acid compositions were determined for serum samples obtained between the 6th and 13th gestational week. Fatty acid data were expressed as the percent of total fatty acids, converted to Z scores and then entered as continuous variables in logistic regression models.
Results: The prevalence of SR was 19.6% and that of MDE was 17.0%. In the adjusted logistic regressions, a higher likelihood of SR was observed among women with higher arachidonic acid levels [AA (20:4, OR=1.45, 95%CI 1.02-2.07] and adrenic acid levels [AdA (22:4, n-6) OR=1.43, 95%CI 1.01-2.041. A higher likelihood of MDE was also observed among women with higher AA levels [OR=1.47, 95%CI 1.03-2.10] and AdA levels [OR=1.59, 95%CI 1.09-2.32].
Conclusion: Higher serum levels of AA and AdA were associated with a greater likelihood of SR and MDE among pregnant Brazilian women. (C) 2013 Elsevier B.V. All rights reserved
C1 [Vaz, Juliana S.; Kac, Gilberto] Univ Fed Rio de Janeiro, Josue de Castro Nutr Inst, Nutr Epidemiol Observ, BR-21941590 Rio De Janeiro, RJ, Brazil.
[Nardi, Antonio E.] Univ Fed Rio de Janeiro, Inst Psychiat, Natl Inst Sci & Technol Translat Med, Lab Pan & Respirat, BR-21941590 Rio De Janeiro, RJ, Brazil.
[Hibbeln, Joseph R.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
RP Kac, G (reprint author), Univ Fed Rio de Janeiro, Josue de Castro Nutr Inst, Dept Social & Appl Nutr, Ave Carlos Chagas Filho,373 CCS Bloco J-2 Ander,S, BR-21941590 Rio De Janeiro, RJ, Brazil.
EM gilberto.kac@gmail.com
RI Kac, Gilberto/H-6862-2012; Vaz, Juliana/A-5645-2012
OI Kac, Gilberto/0000-0001-8603-9077; Vaz, Juliana/0000-0002-2880-767X
FU Brazilian National Research Council (CNPq); National Institutes of
Translational in Medicine (INCT-MT); Carlos Chagas Filho Research
Support Foundation (FAPERJ)
FX This study was supported by Brazilian National Research Council (CNPq),
National Institutes of Translational in Medicine (INCT-MT), Carlos
Chagas Filho Research Support Foundation (FAPERJ), and by the Division
of Intramural Basic and Clinical Research, National Institute on Alcohol
Abuse and Alcoholim, National Institutes of Health, Bethesda, MD, USA.
Nardi and Kac are research fellows from CNPq. Vaz is a recipient of a
scholarship from Coordination for the Training and Improvement of Higher
Education Personnel (CAPES).
NR 48
TC 13
Z9 13
U1 3
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JAN
PY 2014
VL 152
BP 76
EP 82
DI 10.1016/j.jad.2013.04.045
PG 7
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 262UP
UT WOS:000327763600010
PM 23726775
ER
PT J
AU Friedman, ES
Calabrese, JR
Ketter, TA
Leon, AC
Thase, ME
Bowden, CL
Sylvia, LG
Ostracher, MJ
Severe, J
Iosifescu, DV
Nierenberg, AA
Reilly-Harrington, NA
AF Friedman, E. S.
Calabrese, J. R.
Ketter, T. A.
Leon, A. C.
Thase, M. E.
Bowden, C. L.
Sylvia, L. G.
Ostracher, M. J.
Severe, J.
Iosifescu, D. V.
Nierenberg, A. A.
Reilly-Harrington, N. A.
TI Using comparative effectiveness design to improve the generalizability
of bipolar treatment trials data: Contrasting LiTMUS baseline data with
pre-existing placebo controlled trials
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Comparative effectiveness; Bipolar; Baseline characteristics;
Generalizability
ID PSYCHOTROPIC-DRUG PRESCRIPTION; LITHIUM MAINTENANCE TREATMENT;
CONTROLLED 18-MONTH TRIAL; I-DISORDER; DOUBLE-BLIND; MOOD STABILIZER;
ACUTE MANIA; DEPRESSION; EFFICACY; LAMOTRIGINE
AB Background: Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The LiTMUS trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity.
Method: To maximize generalizability, LiTMUS used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP >= 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The LiTMUS study design and baseline sociodemographic data were compared to previous efficacy studies.
Results: As compared to the previous bipolar disorder efficacy studies. LiTMUS participants were of similar age, gender, weight and illness severity; however LiTMUS participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity.
Conclusions: LiTMUS was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the LiTMUS study to be a more representative of real world pharmacotherapuetic outcomes.
Limitations: Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. (C) 2013 Published by Elsevier B.V.
C1 [Friedman, E. S.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Calabrese, J. R.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Cleveland, OH 44106 USA.
[Ketter, T. A.; Ostracher, M. J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Leon, A. C.] Weill Cornell Med Coll, New York, NY USA.
[Thase, M. E.] Univ Penn, Philadelphia, PA 19104 USA.
[Bowden, C. L.] Univ Texas Hlth Sci, San Antonio, TX USA.
[Sylvia, L. G.; Nierenberg, A. A.; Reilly-Harrington, N. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Severe, J.] NIMH, Bethesda, MD 20892 USA.
[Iosifescu, D. V.] Mt Sinai Sch Med, New York, NY 10029 USA.
RP Friedman, ES (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM FriedmanE@upmc.edu
OI Ostacher, Michael/0000-0003-0353-7535
FU National Institute of Mental Health [NO1MH80001]
FX This study was support by a grant from the National Institute of Mental
Health, Contract # NO1MH80001.
NR 36
TC 2
Z9 3
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JAN
PY 2014
VL 152
BP 97
EP 104
DI 10.1016/j.jad.2013.05.052
PG 8
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 262UP
UT WOS:000327763600013
PM 23845385
ER
PT J
AU Yan, XX
Ma, C
Gai, WP
Cai, HB
Luo, XG
AF Yan, Xiao-Xin
Ma, Chao
Gai, Wei-Ping
Cai, Huaibin
Luo, Xue-Gang
TI Can BACE1 Inhibition Mitigate Early Axonal Pathology in Neurological
Diseases?
SO JOURNAL OF ALZHEIMERS DISEASE
LA English
DT Review
DE Aging; Alzheimer's disease; anti-amyloid therapy; dementia; dystrophic
neurites; neurodegenerative disorders; neuroplasticity; senile plaques;
synaptic dysfunction
ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE BACE1; TRAUMATIC BRAIN-INJURY;
SPORADIC ALZHEIMERS-DISEASE; OLFACTORY SENSORY NEURONS; PERIPHERAL
NERVOUS-SYSTEM; HUMAN TEMPORAL-LOBE; GAMMA-SECRETASE; A-BETA; IN-VIVO
AB beta-Secretase-1 (BACE1) is the rate-limiting enzyme for the genesis of amyloid-beta (A beta) peptides, the main constituents of the amyloid plaques in the brains of Alzheimer's disease (AD) patients. BACE1 is being evaluated as an anti-A beta target for AD therapy. Recent studies indicate that BACE1 elevation is associated with axonal and presynaptic pathology during plaque development. Evidence also points to a biological role for BACE1 in axonal outgrowth and synapse formation during development. Axonal, including presynaptic, pathology exists in AD as well as many other neurological disorders such as Parkinson's disease, epilepsy, stroke, and trauma. In this review, we discuss pharmaceutical BACE1 inhibition as a therapeutic option for axonal pathogenesis, in addition to amyloid pathology. We first introduce the amyloidogenic processing of amyloid-beta protein precursor and describe the normal expression pattern of the amyloidogenic proteins in the brain, with an emphasis on BACE1. We then address BACE1 elevation relative to amyloid plaque development, followed by updating recent understanding of a neurotrophic role of BACE1 in axon and synapse development. We further elaborate the occurrence of axonal pathology in some other neurological conditions. Finally, we propose pharmacological inhibition of excessive BACE1 activity as an option to mitigate early axonal pathology occurring in AD and other neurological disorders.
C1 [Yan, Xiao-Xin; Luo, Xue-Gang] Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
[Ma, Chao] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Anat Histol & Embryol, Beijing 100730, Peoples R China.
[Ma, Chao] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Gai, Wei-Ping] Flinders Univ S Australia, Sch Med, Dept Human Physiol, Bedford Pk, SA 5042, Australia.
[Gai, Wei-Ping] Flinders Univ S Australia, Sch Med, Ctr Neurosci, Bedford Pk, SA 5042, Australia.
[Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Yan, XX (reprint author), Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China.
EM yanxiaoxin@csu.edu.cn
RI Gai, Wei-Ping/A-3700-2008
FU Natural Science Foundation of China [81171091, 81171160]; Intramural
research program of National Institute on Aging; XYSM-PUMC Human Brain
Banking Consortium
FX This work is supported by the Natural Science Foundation of China
(81171091 to XXY, 81171160 to XGL), the Intramural research program of
National Institute on Aging (to HC), and the XYSM-PUMC Human Brain
Banking Consortium.
NR 153
TC 6
Z9 7
U1 0
U2 12
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 2014
VL 38
IS 4
BP 705
EP 718
DI 10.3233/JAD-131400
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 270RB
UT WOS:000328335100002
PM 24081378
ER
PT J
AU Zachariou, V
Klatzky, R
Behrmann, M
AF Zachariou, Valentinos
Klatzky, Roberta
Behrmann, Marlene
TI Ventral and Dorsal Visual Stream Contributions to the Perception of
Object Shape and Object Location
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID HUMAN EXTRASTRIATE CORTEX; STRIATE CORTEX; ATTENTION; PATHWAYS;
ORGANIZATION; RECOGNITION; REPRESENTATIONS; POSITION; LESIONS; VISION
AB Growing evidence suggests that the functional specialization of the two cortical visual pathways may not be as distinct as originally proposed. Here, we explore possible contributions of the dorsal where/how visual stream to shape perception and, conversely, contributions of the ventral what visual stream to location perception in human adults. Participants performed a shape detection task and a location detection task while undergoing fMRI. For shape detection, comparable BOLD activation in the ventral and dorsal visual streams was observed, and the magnitude of this activation was correlated with behavioral performance. For location detection, cortical activation was significantly stronger in the dorsal than ventral visual pathway and did not correlate with the behavioral outcome. This asymmetry in cortical profile across tasks is particularly noteworthy given that the visual input was identical and that the tasks were matched for difficulty in performance. We confirmed the asymmetry in a subsequent psychophysical experiment in which participants detected changes in either object location or shape, while ignoring the other, task-irrelevant dimension. Detection of a location change was slowed by an irrelevant shape change matched for difficulty, but the reverse did not hold. We conclude that both ventral and dorsal visual streams contribute to shape perception, but that location processing appears to be essentially a function of the dorsal visual pathway.
C1 [Zachariou, Valentinos; Klatzky, Roberta; Behrmann, Marlene] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA.
RP Zachariou, V (reprint author), NIH, Lab Brain & Cognit, Bethesda, MD 20814 USA.
EM zachariouv@mail.nih.gov
OI Behrmann, Marlene/0000-0002-3814-1015
FU MNTP program at the Center for the Neural Basis of Cognition, University
of Pittsburgh [NIH/NIDA R90 DA023420: MNTP]; Carnegie Mellon University;
National Institutes of Health [MH54246]
FX This research was supported by a fellowship from the MNTP program
(NIH/NIDA R90 DA023420: MNTP) at the Center for the Neural Basis of
Cognition, University of Pittsburgh and Carnegie Mellon University and
by a grant from the National Institutes of Health to M. B. (MH54246).
NR 35
TC 14
Z9 14
U1 2
U2 18
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
EI 1530-8898
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JAN
PY 2014
VL 26
IS 1
BP 189
EP 209
DI 10.1162/jocn_a_00475
PG 21
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 258AU
UT WOS:000327430900016
PM 24001005
ER
PT J
AU Aung, PP
Climent, F
Muzzafar, T
Curry, JL
Patel, KP
Servitje, O
Prieto, VG
Duvic, M
Jaffe, ES
Torres-Cabala, CA
AF Aung, Phyu Phyu
Climent, Fina
Muzzafar, Tariq
Curry, Jonathan L.
Patel, Keyur P.
Servitje, Octavio
Prieto, Victor G.
Duvic, Madeleine
Jaffe, Elaine S.
Torres-Cabala, Carlos A.
TI Immunophenotypic shift of CD4 and CD8 antigen expression in primary
cutaneous T-cell lymphomas: a clinicopathologic study of three cases
SO JOURNAL OF CUTANEOUS PATHOLOGY
LA English
DT Article
DE cutaneous T-cell lymphoma (CTCL); immunohistochemistry; immunophenotype;
mycosis fungoides (MF); T-cell receptor gene rearrangement (PCR
technique)
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MYCOSIS-FUNGOIDES; PHENOTYPE; RELAPSE;
DIAGNOSIS; PATIENT
AB Primary cutaneous T-cell lymphomas (CTCL) comprise a heterogeneous group of neoplasms with diverse clinical behavior. Mycosis fungoides (MF) is the most common type of CTCL. Immunophenotypical shift during progression of the disease is a rare event and its significance is unknown. We present three primary CTCL cases that showed an immunophenotypical shift and poor prognosis. Conventional hematoxylin/eosin and immunohistochemical-stained sections were examined in all the cases. Molecular analysis for rearrangement of the T-cell receptor (TCR) gene was performed in two cases. One case was classified as MF, while the other two lacked epidermotropism, and were considered primary cutaneous peripheral T-cell lymphoma (PTCL), NOS. Two cases were CD3+/CD4+ and one case was CD3+/CD8+ at diagnosis. The first two patients suffered many relapses and eventually, new CTCL lesions with a CD3+/CD8+ phenotype were observed. Both cases revealed identical clonal TCR rearrangements on the initial and late lesions, supporting the interpretation of a single clonal proliferation with different phenotypes. The third case progressed with skin recurrences and pulmonary lesions with a predominant CD3+/CD4+/CD8- phenotype. All cases manifested poor prognosis and two patients died of lymphoma. Immunophenotypical shift between CD4 and CD8 in CTCL seems to be a rare phenomenon that may be associated with disease progression.
C1 [Aung, Phyu Phyu; Jaffe, Elaine S.] NCI, NIH, Bethesda, MD USA.
[Climent, Fina; Servitje, Octavio] Hosp Univ Bellvitge, Barcelona, Spain.
[Muzzafar, Tariq; Curry, Jonathan L.; Patel, Keyur P.; Prieto, Victor G.; Duvic, Madeleine; Torres-Cabala, Carlos A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Torres-Cabala, CA (reprint author), UTMD Anderson Canc Ctr, Dermatopathol Sect, Dept Pathol, 1515 Holcombe Blvd,Unit 85,Room B4-4610 B, Houston, TX 77030 USA.
EM ctcabala@mdanderson.org
NR 19
TC 5
Z9 5
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0303-6987
EI 1600-0560
J9 J CUTAN PATHOL
JI J. Cutan. Pathol.
PD JAN
PY 2014
VL 41
IS 1
BP 51
EP 57
DI 10.1111/cup.12252
PG 7
WC Dermatology; Pathology
SC Dermatology; Pathology
GA 269VV
UT WOS:000328271400010
PM 24151865
ER
PT S
AU De Wever, O
Hendrix, A
De Boeck, A
Eertmans, F
Westbroek, W
Braems, G
Bracke, ME
AF De Wever, Olivier
Hendrix, An
De Boeck, Astrid
Eertmans, Frank
Westbroek, Wendy
Braems, Geert
Bracke, Marc E.
BE Dwek, M
Brooks, SA
TI Single Cell and Spheroid Collagen Type I Invasion Assay
SO METASTASIS RESEARCH PROTOCOLS, 2ND EDITION
SE Methods in Molecular Biology
LA English
DT Article; Book Chapter
DE Tumor stroma; Heterotypic cellular signalling; Actin cytoskeleton; 3D
matrices
ID COLON-CANCER CELLS; TUMOR-CELLS; TGF-BETA; CADHERIN; DIFFERENTIATION;
MYOFIBROBLASTS; TRANSITION; SUPPRESSOR; PHENOTYPE; MIGRATION
AB Tumor invasion is the outcome of a complex interplay between cancer cells and the stromal environment and requires the infiltration of a dense, cross-linked meshwork of collagen type I extracellular matrix. We use a membrane-free single-cell and spheroid-based complementary model to study cancer invasion through native collagen type I matrices. Cell morphology is preserved during the assays allowing real-time monitoring of invasion-induced changes in cell structure and F-actin organization. Combination of these models with computerized quantification permits the calculation of highly reproducible and operator-independent data. These assays are versatile in the use of fluorescent probes and have a flexible kinetic endpoint. Once the optimal experimental conditions are empirically determined, the collagen type I invasion assays can be used for preclinical validation of small-molecule inhibitors targeting invasion. Initiation and monitoring of the single-cell and spheroid invasion model can be achieved in 8 h (over 3 days) and in 14 h (over 5 days), respectively.
C1 [De Wever, Olivier; De Boeck, Astrid; Eertmans, Frank; Bracke, Marc E.] Ghent Univ Hosp, Dept Radiotherapy & Nucl Med, Lab Expt Canc Res, Ghent, Belgium.
[Hendrix, An] Ghent Univ Hosp, Dept Med Oncol, Ghent, Belgium.
[Westbroek, Wendy] NHGRI, NIH, Bethesda, MD 20892 USA.
[Braems, Geert] Ghent Univ Hosp, Dept Gynaecol, Ghent, Belgium.
RP De Wever, O (reprint author), Ghent Univ Hosp, Dept Radiotherapy & Nucl Med, Lab Expt Canc Res, Ghent, Belgium.
OI Eertmans, Frank/0000-0002-2820-7658
NR 23
TC 4
Z9 4
U1 3
U2 18
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA
SN 1064-3745
BN 978-1-4614-8243-7; 978-1-4614-8244-4
J9 METHODS MOL BIOL
JI Methods Mol. Biol.
PY 2014
VL 1070
BP 13
EP 35
DI 10.1007/978-1-4614-8244-4_2
D2 10.1007/978-1-4614-8244-4
PG 23
WC Biochemical Research Methods; Oncology; Cell Biology
SC Biochemistry & Molecular Biology; Oncology; Cell Biology
GA BJH01
UT WOS:000328149800003
PM 24092429
ER
PT J
AU Grunseich, C
Rinaldi, C
Fischbeck, KH
AF Grunseich, C.
Rinaldi, C.
Fischbeck, K. H.
TI Spinal and bulbar muscular atrophy: pathogenesis and clinical management
SO ORAL DISEASES
LA English
DT Review
DE genetics; craniofacial; motor neuron disease; spinal and bulbar muscular
atrophy; Kennedy's disease; weakness
ID TRANSGENIC MOUSE MODEL; AMYOTROPHIC-LATERAL-SCLEROSIS; ANDROGEN RECEPTOR
GENE; KENNEDY-DISEASE; EXPANDED POLYGLUTAMINE; PHENOTYPIC-EXPRESSION;
PATHOLOGY; PROTEIN; REPEAT; NEURODEGENERATION
AB Spinal and bulbar muscular atrophy, or Kennedy's disease, is an X-linked motor neuron disease caused by polyglutamine repeat expansion in the androgen receptor. The disease is characterised by weakness, atrophy and fasciculations in the limb and bulbar muscles. Affected males may have signs of androgen insensitivity, such as gynaecomastia and reduced fertility. Neurophysiological studies are typically consistent with diffuse denervation atrophy, and serum creatine kinase is usually elevated 2-5 times above normal. Progression of the disease is slow, and the focus of spinal and bulbar muscular atrophy (SBMA) management is to prevent complications.
C1 [Grunseich, C.; Rinaldi, C.; Fischbeck, K. H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Grunseich, C (reprint author), NIH, 35 Convent Dr,Rm 2A-1010, Bethesda, MD 20892 USA.
EM christopher.grunseich@nih.gov
FU Intramural NIH HHS [ZIA NS003038-07]
NR 34
TC 11
Z9 12
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD JAN
PY 2014
VL 20
IS 1
BP 6
EP 9
DI 10.1111/odi.12121
PG 4
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 265NT
UT WOS:000327959500002
PM 23656576
ER
PT J
AU Bensen, JT
Xu, ZL
McKeigue, PM
Smith, GJ
Fontham, ETH
Mohler, JL
Taylor, JA
AF Bensen, Jeannette T.
Xu, Zongli
McKeigue, Paul M.
Smith, Gary J.
Fontham, Elizabeth T. H.
Mohler, James L.
Taylor, Jack A.
TI Admixture Mapping of Prostate Cancer in African Americans Participating
in the North Carolina-Louisiana Prostate Cancer Project (PCaP)
SO PROSTATE
LA English
DT Article
DE ancestry informative markers; prostate cancer; African American; mapping
by admixture linkage disequilibrium; MALD; SNP
ID GENOME-WIDE ASSOCIATION; TRANSFER-RNA GENES; ADMIXED POPULATIONS;
PROSPECTIVE IDENTIFICATION; RISK LOCUS; SUSCEPTIBILITY; ANCESTRY;
SEQUENCE; CELLS; TWINS
AB BACKGROUNDFew genetic risk factors have been uncovered that contribute specifically to the racial disparity in prostate cancer (CaP) observed in African Americans (AA). With the advent of ancestry informative marker (AIM) single nucleotide polymorphism (SNP) panels and powerful genetic strategies such as mapping by admixture linkage disequilibrium (MALD) it is possible to discover genes that underlie ethnic variation in disease risk.
METHODSOne thousand one hundred thirty AA CaP cases enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were genotyped using a 1,509 AIM SNP panel. MALD was performed using ADMIXMAP to test for linkage between CaP risk and ancestry estimates at each AIM SNP.
RESULTSThe largest increase of African ancestry was observed at marker rs12543473 (P=0.0011), located on chromosome 8q24.21, and the greatest excess of European ancestry was observed at marker rs10768140 (P=0.0004) at chromosome 11p13.
CONCLUSIONSThe study confirmed the 8q24 risk loci and identified a novel genomic region on 11p13 that is associated with CaP risk. These findings should be replicated in larger AA populations and combined with fine mapping data to further refine the novel 11p13 CaP risk loci. Prostate 74:1-9, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Bensen, Jeannette T.] Univ N Carolina, Dept Epidemiol, Div Urol, Chapel Hill, NC USA.
[Bensen, Jeannette T.; Mohler, James L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Urol, Chapel Hill, NC 27599 USA.
[Xu, Zongli; Taylor, Jack A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[McKeigue, Paul M.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Smith, Gary J.; Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA.
[Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA.
[Mohler, James L.] SUNY Buffalo, Dept Urol, Sch Med & Biotechnol, Buffalo, NY 14260 USA.
[Mohler, James L.] Univ N Carolina, Dept Surg, Div Urol, Chapel Hill, NC USA.
[Taylor, Jack A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Taylor, JA (reprint author), NIEHS, MD A3-05,111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM taylor@niehs.nih.gov
OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398
FU National Institute of Environmental Health Sciences, NIH [Z01 ES049033]
FX Grant sponsor: National Institute of Environmental Health Sciences, NIH;
Grant number: Z01 ES049033.
NR 53
TC 9
Z9 9
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD JAN
PY 2014
VL 74
IS 1
BP 1
EP 9
DI 10.1002/pros.22722
PG 9
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 263QV
UT WOS:000327824000001
PM 24037755
ER
PT S
AU Pardeshi, R
Chaudhuri, BB
Hangarge, M
Santosh, KC
AF Pardeshi, Rajmohan
Chaudhuri, B. B.
Hangarge, Mallikarjun
Santosh, K. C.
GP IEEE
TI Automatic Handwritten Indian Scripts Identification
SO 2014 14th International Conference on Frontiers in Handwriting
Recognition (ICFHR)
SE International Conference on Handwriting Recognition
LA English
DT Proceedings Paper
CT 14th International Conference on Frontiers in Handwriting Recognition
(ICFHR)
CY SEP 01-04, 2014
CL Hersonissos, GREECE
SP MyScript Labs, NeuroScript, Google, IAPR, Demokritos, Natl Ctr Sci Res, Athena Res Ctr
DE The Radon transform; wavelet transform; discrete cosine transform;
statistical filters; Indian script identification
ID TEXTURE; IMAGES
AB Since OCR engines are usually script-dependent, automatic text recognition in multi-script document requires a pre-processor module that identifies the scripts. Based on this motivation, in this paper, we present a word level handwritten Indian script identification technique. To handle this, words are first segmented by morphological dilation and performed connected component labelling. We then employ the Radon transform, discrete wavelet transform, statistical filters and discrete cosine transform to extract the directional multi-resolution spatial features. We tested the features by using linear discriminant analysis, support vector machine and K-nearest neighbour classifiers over 11 different major Indian scripts (including Roman) in bi-script and tri-script scenario. In our tests, we have achieved maximum accuracies of 98% and 96% for bi-script and tri-scipt respectively.
C1 [Pardeshi, Rajmohan; Hangarge, Mallikarjun] Karnatak Arts Sci & Commerce Coll, Dept Comp Sci, Bidar, India.
[Chaudhuri, B. B.] Indian Stat Inst, Comp Vis & Pattern Recognit Unit, Kolkata 700108, India.
[Santosh, K. C.] NIH, US Natl Lib Med NLM, Bethesda, MD 20894 USA.
RP Pardeshi, R (reprint author), Karnatak Arts Sci & Commerce Coll, Dept Comp Sci, Bidar, India.
EM rajkascc@ieee.org; bbcisical@gmail.com; mhangarge@yahoo.co.in;
santosh.kc@nih.gov
OI Pardeshi, Rajmohan/0000-0002-8204-8651
NR 19
TC 6
Z9 6
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2167-6445
BN 978-1-4799-4335-7
J9 INT CONF FRONT HAND
PY 2014
BP 375
EP 380
DI 10.1109/ICFHR.2014.69
PG 6
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems
SC Computer Science
GA BG8YH
UT WOS:000392822500061
ER
PT S
AU Vajda, S
Szocs, B
AF Vajda, Szilard
Szocs, Barna
GP IEEE
TI A Neural Network Based Distance Function for the k-Nearest Neighbor
Classifier
SO 2014 14th International Conference on Frontiers in Handwriting
Recognition (ICFHR)
SE International Conference on Handwriting Recognition
LA English
DT Proceedings Paper
CT 14th International Conference on Frontiers in Handwriting Recognition
(ICFHR)
CY SEP 01-04, 2014
CL Hersonissos, GREECE
SP MyScript Labs, NeuroScript, Google, IAPR, Demokritos, Natl Ctr Sci Res, Athena Res Ctr
DE distance function; k-nearest neighbor; metric learning
AB Due to its simplicity and intuitivity, the k-nearest neighbor method is one of the most commonly used technique to address different classification problems. However, to apply such a classification technique, a distance metric is to be considered to define a certain distance in the feature space. Usually classic norms such as Minkowski, Mahalanobis, etc. are used, but even though they can be applied to all type of feature spaces, there is a lack of specificity of these methods for the data in use. Our goal is to learn the distance function rather than providing an explicit one, by exploiting the specificity of the data. Several neural networks are trained to estimate the distance between two patterns, adapting the weight of the networks accordingly. For the experimental setup, we considered three well-known benchmark, publicly available data collections: MNIST digit data, Opt-digits data, and the Lampung character collection for Arabic handwritten digits and Indonesian handwritten Lampung characters, respectively. The results of k-nearest neighbor considering network based estimated distance between the handwritten digits/characters proved to be very promising.
C1 [Vajda, Szilard] NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
[Szocs, Barna] Univ Babes Bolyai, Dept Comp Sci, Fac Math & Comp Sci, Cluj Napoca, Romania.
RP Vajda, S (reprint author), NIH, US Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM szilard.vajda@nih.gov
FU TAMOP [4.2.4. A/2-11-1-2012-0001]; European Social Fund
FX This research was realized partially in the frame of TAMOP 4.2.4.
A/2-11-1-2012-0001, a National Excellence Program - elaborating and
operating an inland student and researcher personal support system. The
project was subsidized by the European Union and co-financed by the
European Social Fund,
NR 18
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2167-6445
BN 978-1-4799-4335-7
J9 INT CONF FRONT HAND
PY 2014
BP 429
EP 433
DI 10.1109/ICFHR.2014.78
PG 5
WC Computer Science, Artificial Intelligence; Computer Science, Information
Systems
SC Computer Science
GA BG8YH
UT WOS:000392822500070
ER
PT S
AU Yao, J
Burns, JE
Getty, S
Stieger, J
Summers, RM
AF Yao, Jianhua
Burns, Joseph E.
Getty, Sasha
Stieger, James
Summers, Ronald M.
GP IEEE
TI AUTOMATED EXTRACTION OF ANATOMIC LANDMARKS ON VERTEBRAE BASED ON
ANATOMIC KNOWLEDGE AND GEOMETRICAL CONSTRAINTS
SO 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT 11th IEEE International Symposium on Biomedical Imaging (ISBI)
CY APR 29-MAY 02, 2014
CL Beijing, PEOPLES R CHINA
SP IEEE, IEEE Engn Med & Biol Soc, IEEE Signal Proc Soc, EGI, GE, Kitware
DE computer aided detection; vertebrae; anatomic landmark
ID CT IMAGES; SPINE; SURGERY; MODELS
AB The determination of anatomic landmarks is an essential step in modeling, shape analysis, segmentation, and registration of the spine, as well as in spine interventions. In this paper, we propose a method to automatically partition each vertebra into anatomic substructures and extract the relevant anatomic landmarks. Anatomic knowledge is integrated in geometrical modeling for the landmark localization. Each vertebra is automatically partitioned into four substructures, and 43 anatomical landmarks are identified. The locations were validated with manual annotation from medical experts. The results showed that the automatic landmarks agreed with manually labeled reference standard landmarks (1.9 +/- 1.3mm).
C1 [Yao, Jianhua; Stieger, James; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Burns, Joseph E.; Getty, Sasha] Univ Calif Irvine, Sch Med, Dept Radiol Sci, Irvine, CA 92717 USA.
RP Yao, J (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural Research Program of NIH, Clinical Center
FX This research was supported in part by the Intramural Research Program
of NIH, Clinical Center.
NR 10
TC 2
Z9 2
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4673-1961-4
J9 I S BIOMED IMAGING
PY 2014
BP 397
EP 400
PG 4
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BG8WQ
UT WOS:000392750900099
ER
PT S
AU Liu, JM
Zhao, J
Hoffman, J
Yao, JH
Lu, L
Turkbey, EB
Kim, C
Summers, RM
AF Liu, Jiamin
Zhao, Jocelyn
Hoffman, Joanne
Yao, Jianhua
Lu, Le
Turkbey, Evrim B.
Kim, Christine
Summers, Ronald M.
GP IEEE
TI DETECTION AND STATION MAPPING OF MEDIASTINAL LYMPH NODES ON THORACIC
COMPUTED TOMOGRAPHY USING SPATIAL PRIOR FROM MULTI-ATLAS LABEL FUSION
SO 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT 11th IEEE International Symposium on Biomedical Imaging (ISBI)
CY APR 29-MAY 02, 2014
CL Beijing, PEOPLES R CHINA
SP IEEE, IEEE Engn Med & Biol Soc, IEEE Signal Proc Soc, EGI, GE, Kitware
DE lymph node detection; Hessian analysis; spatial prior; multi-atlas label
fusion
AB Lymph nodes play an important role in clinical practice but detection is challenging due to low contrast surrounding structures and variable size and shape. In this paper, we propose a fully automatic method for mediastinal lymph node detection and station mapping on thoracic CT scans. First, lungs are automatically segmented to locate the mediastinum region. Shape features by Hessian analysis, local scale, and circular transformation are computed at each voxel. Spatial prior distribution is determined based on the identification of 11 anatomical structures by using multi-atlas label fusion. Shape features and spatial prior are then integrated for lymph node detection. The detected candidates are segmented by curve evolution. Characteristic features are calculated on the segmented lymph nodes and support vector machine is utilized for classification and false positive reduction. We applied our method to 20 patients with 62 enlarged mediastinal lymph nodes. The system achieved a significant improvement with 80% sensitivity at 8 false positives per patient with spatial prior compared to 45% sensitivity at 8 false positives per patient without a spatial prior. With the segmentation of spatial anatomic structures, 88% of mediastinal lymph nodes are correctly mapped to their stations.
C1 [Liu, Jiamin; Zhao, Jocelyn; Hoffman, Joanne; Yao, Jianhua; Lu, Le; Turkbey, Evrim B.; Kim, Christine; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA.
RP Liu, JM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Radiol & Imaging Sci, Ctr Clin, Bldg 10 Room 1C224 MSC 1182, Bethesda, MD 20892 USA.
NR 14
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4673-1961-4
J9 I S BIOMED IMAGING
PY 2014
BP 1107
EP 1110
PG 4
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BG8WQ
UT WOS:000392750900275
ER
PT S
AU Kang, X
Zhao, Q
Sharma, K
Shekhar, R
Wood, BJ
Linguraru, MG
AF Kang, Xin
Zhao, Qian
Sharma, Karun
Shekhar, Raj
Wood, Bradford J.
Linguraru, Marius George
GP IEEE
TI AUTOMATIC LABELING OF LIVER VEINS IN CT BY PROBABILISTIC BACKWARD
TRACING
SO 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI)
SE IEEE International Symposium on Biomedical Imaging
LA English
DT Proceedings Paper
CT 11th IEEE International Symposium on Biomedical Imaging (ISBI)
CY APR 29-MAY 02, 2014
CL Beijing, PEOPLES R CHINA
SP IEEE, IEEE Engn Med & Biol Soc, IEEE Signal Proc Soc, EGI, GE, Kitware
ID SEGMENTATION; VASCULATURE; IMAGES
AB The mapping and labeling of the major intra-hepatic blood vessels may facilitate planning liver interventions and surgery. However, the automatic labeling of liver veins is challenging due to imperfect segmentations caused by partial volume effects and image resolution that result in undesirable false connections between hepatic and portal veins. In this paper, we propose a novel method to model the continuity of consecutive venous branches in a probabilistic manner. Then the model is automatically labeled via inference. The method incorporates low-level metrics for neighboring nodes and mid-level metrics for neighboring branches. Making use of these metrics, the automatic labeling becomes a probabilistic tracing procedure starting from each end nodes of the vessel skeleton. The method has only one free parameter whose value is not critical to labeling results. Experiments using data from healthy and pathological patients were performed and the results illustrate an accuracy of 0.97 +/- 0.08.
C1 [Kang, Xin; Zhao, Qian; Sharma, Karun; Shekhar, Raj; Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Sharma, Karun] Childrens Natl Med Ctr, Dept Diagnost & Intervent Radiol, Washington, DC 20010 USA.
[Shekhar, Raj; Linguraru, Marius George] George Washington Univ, Sch Med & Hlth Sci, Dept Radiol, Washington, DC 20037 USA.
[Shekhar, Raj; Linguraru, Marius George] George Washington Univ, Sch Med & Hlth Sci, Dept Pediatrics, Washington, DC 20037 USA.
[Wood, Bradford J.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Kang, X (reprint author), Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
EM xkang@cnmc.org; qzhao@cnmc.org; kvsharma@cnmc.org; rshekhar@cnmc.org;
bwood@cc.nih.gov; mlingura@cnmc.org
FU Government of Abu Dhabi to Children's National Medical Center;
Intramural Research Program of the National Institutes of Health,
Clinical Center
FX This project was supported in part by a philanthropic gift from the
Government of Abu Dhabi to Children's National Medical Center and the
Intramural Research Program of the National Institutes of Health,
Clinical Center.
NR 15
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1945-7928
BN 978-1-4673-1961-4
J9 I S BIOMED IMAGING
PY 2014
BP 1115
EP 1118
PG 4
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA BG8WQ
UT WOS:000392750900277
ER
PT J
AU Crespo, LG
Giesy, DP
Kenny, SP
AF Crespo, Luis G.
Giesy, Daniel P.
Kenny, Sean P.
GP IEEE
TI Interval Predictor Models with a Formal Characterization of Uncertainty
and Reliability
SO 2014 IEEE 53RD ANNUAL CONFERENCE ON DECISION AND CONTROL (CDC)
LA English
DT Proceedings Paper
CT IEEE 53rd Annual Conference on Decision and Control (CDC)
CY DEC 15-17, 2014
CL Los Angeles, CA
SP IEEE, MathWorks, Springer, Altair, dSPACE, Journal Franklin Inst, Soc Ind & Appl Math, United Technologies Res Ctr, Wolfram, EBSCO Informat Serv, Inst Engn & Technol, Now, Taylor & Francis, Cogent Engn
AB This paper develops techniques for constructing empirical predictor models based on observations. By contrast to standard models, which yield a single predicted output at each value of the model's inputs, Interval Predictors Models (IPM) yield an interval into which the unobserved output is predicted to fall. The IPMs proposed prescribe the output as an interval valued function of the model's inputs, render a formal description of both the uncertainty in the model's parameters and of the spread in the predicted output. Uncertainty is prescribed as a hyper-rectangular set in the space of model's parameters. The propagation of this set through the empirical model yields a range of outputs of minimal spread containing all (or, depending on the formulation, most) of the observations. Optimization-based strategies for calculating IPMs and eliminating the effects of outliers are proposed. Outliers are identified by evaluating the extent by which they degrade the tightness of the prediction. This evaluation can be carried out while the IPM is calculated. When the data satisfies mild stochastic assumptions, and the optimization program used for calculating the IPM is convex (or, when its solution coincides with the solution to an auxiliary convex program), the model's reliability (that is, the probability that a future observation would be within the predicted range of outputs) can be bounded rigorously by a non-asymptotic formula.
C1 [Crespo, Luis G.] NASA, Langley Res Ctr, NIA, MS 308, Hampton, VA 23681 USA.
[Giesy, Daniel P.; Kenny, Sean P.] NASA, Langley Res Ctr, Hampton, VA 23681 USA.
RP Crespo, LG (reprint author), NASA, Langley Res Ctr, NIA, MS 308, Hampton, VA 23681 USA.
EM Luis.G.Crespo@nasa.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4673-6090-6
PY 2014
BP 5991
EP 5996
PG 6
WC Automation & Control Systems
SC Automation & Control Systems
GA BE2TY
UT WOS:000370073806027
ER
PT J
AU Zhang, GQ
Zhu, W
Sun, MM
Tao, SQ
Bodenreider, O
Cui, LC
AF Zhang, Guo-Qiang
Zhu, Wei
Sun, Mengmeng
Tao, Shiqiang
Bodenreider, Olivier
Cui, Licong
GP IEEE
BE Lin, J
Hu, XH
Chang, W
Nambiar, R
Aggarwal, C
Cercone, N
Honavar, V
Huan, J
Mobasher, B
Pyne, S
TI MaPLE: A MapReduce Pipeline for Lattice-based Evaluation and Its
Application to SNOMED CT
SO 2014 IEEE INTERNATIONAL CONFERENCE ON BIG DATA (BIG DATA)
LA English
DT Proceedings Paper
CT IEEE International Conference on Big Data
CY OCT 27-30, 2014
CL Washington, DC
SP IEEE, IEEE Comp Soc, ELSEVIER, Natl Sci Fdn, CISCO, CCF
ID HIERARCHIES
AB Non-lattice fragments are often indicative of structural anomalies in ontological systems and, as such, represent possible areas of focus for subsequent quality assurance work. However, extracting the non-lattice fragments in large ontological systems is computationally expensive if not prohibitive, using a traditional sequential approach. In this paper we present a general MapReduce pipeline, called MaPLE (MapReduce Pipeline for Lattice-based Evaluation), for extracting non-lattice fragments in large partially ordered sets and demonstrate its applicability in ontology quality assurance. Using MaPLE in a 30-node Hadoop local cloud, we systematically extracted non-lattice fragments in 8 SNOMED CT versions from 2009 to 2014 (each containing over 300k concepts), with an average total computing time of less than 3 hours per version. With dramatically reduced time, MaPLE makes it feasible not only to perform exhaustive structural analysis of large ontological hierarchies, but also to systematically track structural changes between versions. Our change analysis showed that the average change rates on the non-lattice pairs are up to 38.6 times higher than the change rates of the background structure (concept nodes). This demonstrates that fragments around non-lattice pairs exhibit significantly higher rates of change in the process of ontological evolution.
C1 [Zhang, Guo-Qiang; Zhu, Wei; Sun, Mengmeng; Tao, Shiqiang; Cui, Licong] Case Western Reserve Univ, Dept Elect Engn & Comp Sci, Cleveland, OH 44106 USA.
[Bodenreider, Olivier] Natl Lib Med, Bethesda, MD 20892 USA.
RP Zhang, GQ (reprint author), Case Western Reserve Univ, Dept Elect Engn & Comp Sci, Cleveland, OH 44106 USA.
NR 18
TC 2
Z9 2
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4799-5666-1
PY 2014
BP 754
EP 759
PG 6
WC Computer Science, Information Systems; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA BF2FK
UT WOS:000380462900099
ER
PT J
AU Ewing, ET
Gad, S
Ramakrishnan, N
Reznick, JS
AF Ewing, E. Thomas
Gad, Samah
Ramakrishnan, Naren
Reznick, Jeffrey S.
GP IEEE
BE Lin, J
Hu, XH
Chang, W
Nambiar, R
Aggarwal, C
Cercone, N
Honavar, V
Huan, J
Mobasher, B
Pyne, S
TI Understanding the Role of Medical Experts during a Public Health Crisis
Digital Tools and Library Resources for Research on the 1918 Spanish
Influenza
SO 2014 IEEE INTERNATIONAL CONFERENCE ON BIG DATA (BIG DATA)
LA English
DT Proceedings Paper
CT IEEE International Conference on Big Data
CY OCT 27-30, 2014
CL Washington, DC
SP IEEE, IEEE Comp Soc, ELSEVIER, Natl Sci Fdn, CISCO, CCF
DE History; Disease; Data Mining; Public Health; Topic Modeling
AB Humanities scholars, particularly historians of health and disease, can benefit from digitized library collections and tools such as topic modeling. Using a case study from the 1918 Spanish Flu epidemic, this paper explores the application of a big humanities approach to understanding the impact of a public health official on the course of the disease and the response of the public, as documented through digitized newspapers and medical periodicals.
C1 [Ewing, E. Thomas] Virginia Tech, Dept Hist, Blacksburg, VA 24061 USA.
[Gad, Samah; Ramakrishnan, Naren] Virginia Tech, Dept Comp Sci, Discovery Analyt Ctr, Arlington, VA 22203 USA.
[Reznick, Jeffrey S.] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA.
RP Ewing, ET (reprint author), Virginia Tech, Dept Hist, Blacksburg, VA 24061 USA.
NR 30
TC 0
Z9 0
U1 1
U2 1
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4799-5666-1
PY 2014
PG 8
WC Computer Science, Information Systems; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA BF2FK
UT WOS:000380462900248
ER
PT S
AU Ma, KD
Canepa, M
Strait, JB
Shatkay, H
AF Ma, Kaidi
Canepa, Marco
Strait, James B.
Shatkay, Hagit
BE Zheng, H
Hu, X
Berrar, D
Wang, Y
Dubitzky, W
Hao, JK
Cho, KH
Gilbert, D
TI Using Unsupervised Learning to Determine Risk Level for Left Ventricular
Diastolic Dysfunction
SO 2014 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE
(BIBM)
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE
BIBM)
CY NOV 02-05, 2014
CL Univ Ulster, Belfast, NORTH IRELAND
SP IEEE, Natl Sci Fdn, Nsilico, Comp Sci Res Inst, BioBusiness, IEEE Comp Soc, Engn Res Inst, Biomed Sci Res Inst
HO Univ Ulster
DE unsupervised learning; clustering; left ventricle diastolic dysfunction;
EM algorithm
ID LEFT ATRIAL VOLUME; HEART-FAILURE; ECHOCARDIOGRAPHY; DIAGNOSIS;
RECOMMENDATIONS
AB Left Ventricular Diastolic Dysfunction (LVDD) is a decompensatory change in the relaxation properties of the heart, the risk for which increases with age. Currently, physicians use a decision-tree-like algorithm to distinguish between discrete LVDD levels. This approach, based on cut-off thresholds, can potentially lead to information loss and possibly to misdiagnosis.
This paper aims to explore an alternative diagnostic method to determine LVDD risk level, taking into account a wide variety of attributes available in patient records, without pre-setting cut-off thresholds. Using a large dataset derived from the Baltimore Longitude Study of Aging (BLSA), and adjusting the data for age and gender, we employ the Chi Square test and the information gain criterion to identify attributes that correlate well with the physician-assigned grades; such attributes are referred to as distinguishing attributes. We then apply the expectation maximization (EM) algorithm, as well as the K-Means, in order to cluster records that are represented using distinguishing attributes.
While clusters resulting from the K-Means are not stable, three stable and tightly-formed clusters, which are obtained from the EM algorithm, roughly correspond to the physician-assigned categories. Based on the results from the EM algorithm, we can compute a patient's probability to have low, high or no risk for LVDD, and use this probability as a basis for defining a risk score to determine the patient's LVDD severity.
C1 [Ma, Kaidi; Shatkay, Hagit] Univ Delaware, Dept Comp & Informat Sci, Newark, DE 19716 USA.
[Canepa, Marco; Strait, James B.] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Canepa, Marco; Strait, James B.] NIA, Lab Cardiovasc Sci, Human Cardiovasc Studies Unit, NIH, Baltimore, MD 21224 USA.
RP Ma, KD (reprint author), Univ Delaware, Dept Comp & Informat Sci, Newark, DE 19716 USA.
EM kdma@udel.edu; marco.canepa@nih.gov; straitj@mail.nih.gov;
shatkay@udel.edu
NR 19
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4799-5669-2
J9 IEEE INT C BIOINFORM
PY 2014
PG 4
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9FO
UT WOS:000377412300233
ER
PT S
AU Morris, SA
Lijowski, M
Gaheen, S
Heiskanen, M
Klemm, J
AF Morris, Stephanie A.
Lijowski, Michal
Gaheen, Sharon
Heiskanen, Mervi
Klemm, Juli
BE Zheng, H
Hu, X
Berrar, D
Wang, Y
Dubitzky, W
Hao, JK
Cho, KH
Gilbert, D
TI caNanoLab: A nanomaterial data repository for biomedical research
SO 2014 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE
(BIBM)
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE
BIBM)
CY NOV 02-05, 2014
CL Univ Ulster, Belfast, NORTH IRELAND
SP IEEE, Natl Sci Fdn, Nsilico, Comp Sci Res Inst, BioBusiness, IEEE Comp Soc, Engn Res Inst, Biomed Sci Res Inst
HO Univ Ulster
DE caNanoLab; nanomaterials; databases; nanomedicine; cancer; biomedical
research
AB The application of nanotechnology to medicine enables the development of research tools, and multifunctional diagnostic and therapeutic agents with the potential to greatly improve the clinical care of patients. Although still an emerging field, nanoinformatics seeks to identify information relevant to nanotechnology research that can be used in knowledge discovery, and in the case of biomedicine, facilitate the advancement of these technologies and tools to the clinical environment through data collection, sharing, validation, and analysis. In this paper, we describe the cancer Nanotechnology Laboratory (caNanoLab) data portal, a public repository for the storage and sharing of well-characterized biomedical nanomaterial data and information, including experimental conditions. caNanoLab also provides access to publications and protocols associated with nanomaterials.
C1 [Morris, Stephanie A.] NCI, Off Canc Nanotechnol Res, NIH, Bethesda, MD 20892 USA.
[Lijowski, Michal] Essential Software Inc, Potomac, MD USA.
[Gaheen, Sharon] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Heiskanen, Mervi; Klemm, Juli] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD USA.
RP Morris, SA (reprint author), NCI, Off Canc Nanotechnol Res, NIH, Bethesda, MD 20892 USA.
EM morriss2@mail.nih.gov; michal.lijowski@essential-soft.com;
gaheens@mail.nih.gov; heiskame@mail.nih.gov; Juli.Klemm@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4799-5669-2
J9 IEEE INT C BIOINFORM
PY 2014
PG 5
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9FO
UT WOS:000377412300118
ER
PT S
AU You, D
Antani, S
Demner-Fushman, D
Thoma, GR
AF You, Daekeun
Antani, Sameer
Demner-Fushman, Dina
Thoma, George R.
BE Zheng, H
Hu, X
Berrar, D
Wang, Y
Dubitzky, W
Hao, JK
Cho, KH
Gilbert, D
TI Biomedical Image Segmentation for Semantic Visual Feature Extraction
SO 2014 IEEE INTERNATIONAL CONFERENCE ON BIOINFORMATICS AND BIOMEDICINE
(BIBM)
SE IEEE International Conference on Bioinformatics and Biomedicine-BIBM
LA English
DT Proceedings Paper
CT IEEE International Conference on Bioinformatics and Biomedicine (IEEE
BIBM)
CY NOV 02-05, 2014
CL Univ Ulster, Belfast, NORTH IRELAND
SP IEEE, Natl Sci Fdn, Nsilico, Comp Sci Res Inst, BioBusiness, IEEE Comp Soc, Engn Res Inst, Biomed Sci Res Inst
HO Univ Ulster
ID RETRIEVAL
AB Biomedical photographs comprise diverse optically acquired images. Accurate classification into meaningful subclasses is valuable in biomedical image retrieval systems. Conventional visual descriptors are limited in their ability to assign semantic labels to images for meaningful retrieval. In this paper we propose a Markov random field (MRF)-based biomedical image segmentation method to segment images into meaningful regions that can be associated with semantic labels. We focus on several tissue image types and develop two MRF models: (i) for tissue image detection from large photograph collection; and, (ii) for region segmentation and semantic labeling. Experimental results demonstrate that our method can detect tissue images in about 82% precision, and our proposed visual descriptors computed from the segmentation results outperform existing visual descriptors. This latter result can be effectively used in biomedical image retrieval systems for retrieving tissue images.
C1 [You, Daekeun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.] NIH, Natl Lib Med, Bethesda, MD 20894 USA.
RP You, D (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA.
EM youdae@med.umich.edu; santani@mail.nih.gov; ddemner@mail.nih.gov;
gthoma@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 2156-1125
BN 978-1-4799-5669-2
J9 IEEE INT C BIOINFORM
PY 2014
PG 4
WC Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology
SC Computer Science; Mathematical & Computational Biology
GA BE9FO
UT WOS:000377412300221
ER
PT S
AU Kim, IC
Le, DX
Thoma, GR
AF Kim, In Cheol
Le, Daniel X.
Thoma, George R.
GP IEEE
TI Automated Method for Extracting "Citation Sentences" from Online
Biomedical Articles Using SVM-based Text Summarization Technique
SO 2014 IEEE INTERNATIONAL CONFERENCE ON SYSTEMS, MAN AND CYBERNETICS (SMC)
SE IEEE International Conference on Systems Man and Cybernetics Conference
Proceedings
LA English
DT Proceedings Paper
CT IEEE International Conference on Systems, Man, and Cybernetics (SMC)
CY OCT 05-08, 2014
CL San Diego, CA
SP IEEE
DE "citation sentence" extraction; online biomedical documents; support
vector machine; MEDLINE (R)
ID CATEGORIZATION
AB Comment-on (CON), a MEDLINE citation field, indicates previously published articles commented on by authors of a given article expressing possibly complimentary or contradictory opinions. Our idea of identifying the CON list for a given article is to first extract all "citation sentences" from the body text, and then to recognize the sentences ("CON sentences") among these that mention CON articles and to analyze the corresponding bibliographic data in the reference section. As a preprocessing step for identifying the CON list, this paper presents a general method for extracting "citation sentences" in the body text of online biomedical articles using a support vector machine (SVM)-based text summarization technique. Input feature vectors for the SVM are created by combining four types of features: 1) word statistics representing how differently a word occurs in "citation sentences" compared to other sentences, and the existence of 2) author names, 3) publication years, and 4) citation tags in a sentence. A rule-based post-processing step is also introduced to further reduce false negative errors in detecting "citation sentences". Experiments on a set of online biomedical articles show that a SVM with a RBF achieves good performance overall in terms of accuracy, precision, recall, and F-measure rates. Our experiments also show that errors in extracting "citation sentences" cause a minor degradation of performance in identifying CON sentences, but can be improved through the proposed rule-based post-processing.
C1 [Kim, In Cheol; Le, Daniel X.; Thoma, George R.] Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
RP Kim, IC (reprint author), Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
SN 1062-922X
BN 978-1-4799-3840-7
J9 IEEE SYS MAN CYBERN
PY 2014
BP 1991
EP 1996
PG 6
WC Computer Science, Artificial Intelligence; Computer Science,
Cybernetics; Computer Science, Information Systems
SC Computer Science
GA BE3MJ
UT WOS:000370963702018
ER
PT J
AU Feng, T
Ahlman, MA
Guo, LH
Bluemke, DA
Tsui, BMW
AF Feng, Tao
Ahlman, Mark A.
Guo, Liheng
Bluemke, David A.
Tsui, Benjamin M. W.
GP IEEE
TI Development and evaluation of two 4D image reconstruction methods with
dual respiratory and cardiac motion compensation for gated cardiac PET
SO 2014 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE
(NSS/MIC)
LA English
DT Proceedings Paper
CT IEEE Nuclear Science Symposium / Medical Imaging Conference (NSS/MIC)
CY NOV 08-15, 2014
CL Seattle, WA
SP IEEE
AB The goal of this study is to develop and evaluate two 4D statistical iterative image reconstruction (SIIR) methods with respiratory motion (RM) and cardiac motion (CM) compensation for improving the detection of motion defects in 4D gated cardiac PET. The first 4D SIIR method, motion correction after reconstruction (MCAR) was developed previously, where the dual RM&CM compensation was achieved by applying the estimated RM&CM transformation to the RM&CM gated reconstructed images after the 4D image reconstruction, respectively. A new motion correction during reconstruction (MCDR) method was developed, where the RM&CM compensation was applied at each iterative step by modeling the estimated RM&CM within the projection and backprojection matrix during the 4D SIIR. In both approaches, the RM and CM were first estimated independently from only the 4D respiratory amplitude-gated and cardiac time-gated reconstructed images, respectively. In both methods, the RM&CM compensated image was transformed back into each cardiac gate to the acquired gated images, and the non-gated attenuation map was transformed using the estimated RM to reduce mis-registration artifacts. The performance of the two methods were evaluated using Monte Carlo simulated gated MP PET images of the 4D XCAT phantom with known true RM&CM at different noise levels, and sample clinical 4D cardiac gated PET studies. The simulation study showed the MCDR provides sharper 4D gated MP PET images with similar to 12% reduction in mean-square-error when compared with those from the MCAR at large number of iterations approaching convergence. The results from using patient data showed the MCDR method provided consistently superior contras-to-noise ratios. We conclude that although the MCDR method is slower, it outperforms the MCAR method in 4D gated cardiac PET image reconstructions. Our findings are supported by simulation and sample patient studies. Human trials using this method are pending.
C1 [Feng, Tao; Guo, Liheng; Tsui, Benjamin M. W.] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Ahlman, Mark A.; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Feng, T (reprint author), Johns Hopkins Univ, Baltimore, MD 21218 USA.
FU NIH intramural research program
FX This research was supported in part by the NIH intramural research
program.
NR 7
TC 0
Z9 0
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4799-6097-2
PY 2014
PG 4
WC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
GA BG9AN
UT WOS:000392917500183
ER
PT J
AU Vajda, S
You, D
Antani, SK
Thoma, GR
AF Vajda, Szilard
You, Daekeun
Antani, Sameer K.
Thoma, George R.
GP IEEE
TI Label the many with a few: Semi-automatic medical image modality
discovery in a large image collection
SO 2014 IEEE Symposium on Computational Intelligence in Healthcare and
e-health (CICARE)
LA English
DT Proceedings Paper
CT IEEE Symposium on Computational Intelligence in Healthcare and e-health
CY DEC 09-12, 2014
CL Orlando, FL
SP IEEE, IEEE Computat Intelligence Soc
AB In this paper we present a fast and effective method for labeling images in a large image collection. Image modality detection has been of research interest for querying multimodal medical documents. To accurately predict the different image modalities using complex visual and textual features, we need advanced classification schemes with supervised learning mechanisms and accurate training labels. Our proposed method, on the other hand, uses a multiview-approach and requires minimal expert knowledge to semi-automatically label the images. The images are first projected in different feature spaces, and are then clustered in an unsupervised manner. Only the cluster representative images are labeled by an expert. Other images from the cluster "inherit" the labels from these cluster representatives. The final label assigned to each image is based on a voting mechanism, where each vote is derived from different feature space clustering. Through experiments we show that using only 0.3% of the labels was sufficient to annotate 300,000 medical images with 49.95% accuracy. Although, automatic labeling is not as precise as manual, it saves approximately 700 hours of manual expert labeling, and may be sufficient for next-stage classifier training. We find that for this collection accuracy improvements are feasible with better disparate feature selection or different filtering mechanisms.
C1 [Vajda, Szilard; Antani, Sameer K.; Thoma, George R.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA.
[You, Daekeun] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
RP Vajda, S (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA.
EM szilard.vajda@nih.gov; youdae@med.umich.edu; sameer.antani@nih.gov;
george.thoma@nih.gov
NR 24
TC 2
Z9 2
U1 0
U2 0
PU IEEE
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017 USA
BN 978-1-4799-5375-2
PY 2014
BP 167
EP 173
PG 7
WC Computer Science, Artificial Intelligence
SC Computer Science
GA BF3TI
UT WOS:000380576000024
ER
PT S
AU Perrin, BS
Pastor, RW
Cotten, M
AF Perrin, B. Scott, Jr.
Pastor, Richard W.
Cotten, Myriam
BE Separovic, F
Naito, A
TI Combining NMR Spectroscopic Measurements and Molecular Dynamics
Simulations to Determine the Orientation of Amphipathic Peptides in
Lipid Bilayers
SO ADVANCES IN BIOLOGICAL SOLID-STATE NMR: PROTEINS AND MEMBRANE-ACTIVE
PEPTIDES
SE New Developments in NMR
LA English
DT Article; Book Chapter
ID SOLID-STATE NMR; MEMBRANE-PROTEINS; TRANSMEMBRANE HELIX; FORCE-FIELD;
ENSEMBLE DYNAMICS; DIPOLAR WAVES; GRAMICIDIN-A; CHARMM; POLYPEPTIDE;
TOPOLOGY
C1 [Perrin, B. Scott, Jr.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Cotten, Myriam] Hamilton Coll, Dept Chem, Clinton, NY 13323 USA.
RP Perrin, BS (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mcotten@hamilton.edu
NR 49
TC 1
Z9 1
U1 1
U2 1
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND
SN 2044-253X
BN 978-1-78262-744-9; 978-1-84973-910-8
J9 NEW DEV NMR
PY 2014
VL 3
BP 18
EP 35
D2 10.1039/9781782627449
PG 18
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Physics,
Atomic, Molecular & Chemical
SC Biochemistry & Molecular Biology; Physics
GA BG3LJ
UT WOS:000387998000003
ER
PT S
AU Qiang, W
Tycko, R
AF Qiang, Wei
Tycko, Robert
BE Separovic, F
Naito, A
TI Solid-State NMR Studies of beta-Amyloid Fibrils and Related Assemblies
SO ADVANCES IN BIOLOGICAL SOLID-STATE NMR: PROTEINS AND MEMBRANE-ACTIVE
PEPTIDES
SE New Developments in NMR
LA English
DT Article; Book Chapter
ID NUCLEAR-MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; ROTATING SOLIDS;
MEMBRANE INTERACTIONS; STRUCTURAL MODEL; CHEMICAL-SHIFT; SUPRAMOLECULAR
STRUCTURE; EXPERIMENTAL CONSTRAINTS; SHEET STRUCTURES; METAL-IONS
C1 [Qiang, Wei; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
NR 96
TC 0
Z9 0
U1 1
U2 1
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND
SN 2044-253X
BN 978-1-78262-744-9; 978-1-84973-910-8
J9 NEW DEV NMR
PY 2014
VL 3
BP 556
EP 576
D2 10.1039/9781782627449
PG 21
WC Biochemical Research Methods; Biochemistry & Molecular Biology; Physics,
Atomic, Molecular & Chemical
SC Biochemistry & Molecular Biology; Physics
GA BG3LJ
UT WOS:000387998000029
ER
PT J
AU Bennett, WD
Ivins, S
Alexis, NE
Wu, J
Bromberg, PA
Brar, SS
Travlos, G
London, S
AF Bennett, W. D.
Ivins, S.
Alexis, N. E.
Wu, J.
Bromberg, P. A.
Brar, S. S.
Travlos, G.
London, S.
TI Effect Of Obesity On Ozone/exercise-Induced Changes In Systemic And
Pulmonary Inflammation In Adult Females
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Bennett, W. D.; Ivins, S.; Alexis, N. E.; Wu, J.; Bromberg, P. A.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA.
[Brar, S. S.; Travlos, G.; London, S.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
EM William_Bennett@med.unc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A5382
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838205009
ER
PT J
AU Boerwinkle, C
Marshall, J
Bryant, J
Gahl, WA
Gunay-Aygun, M
Olivier, KN
AF Boerwinkle, C.
Marshall, J.
Bryant, J.
Gahl, W. A.
Gunay-Aygun, M.
Olivier, K. N.
TI Respiratory Tract Involvement In Alstrom Syndrome
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Boerwinkle, C.; Olivier, K. N.] NIAID, Bethesda, MD 20892 USA.
[Marshall, J.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Bryant, J.; Gahl, W. A.; Gunay-Aygun, M.] NHGRI, NIH, Bethesda, MD 20892 USA.
EM caroline.boerwinkle@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A4695
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838204187
ER
PT J
AU Cheresh, P
Morales-Nebreda, L
Kim, SJ
Yeldandi, A
Williams, DB
Mutlu, GM
Budinger, GS
Schumacker, PT
Bohr, V
Kamp, D
AF Cheresh, P.
Morales-Nebreda, L.
Kim, S-J
Yeldandi, A.
Williams, D. B.
Mutlu, G. M.
Budinger, G. S.
Schumacker, P. T.
Bohr, V.
Kamp, D.
CA RCMB
TI Asbestos-Induced Pulmonary Fibrosis Is Augmented In 8-Oxoguanosine Dna
Glycosylase (ogg1) Knockout Mice
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Cheresh, P.; Morales-Nebreda, L.; Kim, S-J; Yeldandi, A.; Williams, D. B.; Mutlu, G. M.; Budinger, G. S.; Kamp, D.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Schumacker, P. T.] Northwestern Univ, Chicago, IL 60611 USA.
[Bohr, V.] NIA, Baltimore, MD 21224 USA.
EM p-cheresh@northwestern.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A1249
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838200239
ER
PT J
AU Cui, Y
Ma, D
Nwokeji, A
Maynard, D
Gochuico, BR
Handin, R
El-Chemaly, S
AF Cui, Y.
Ma, D.
Nwokeji, A.
Maynard, D.
Gochuico, B. R.
Handin, R.
El-Chemaly, S.
TI Altered Migration Capacity Of Lung Fibroblasts From Patients With
Hermansky-Pudlak Syndrome
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Cui, Y.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Ma, D.; Nwokeji, A.; Handin, R.; El-Chemaly, S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Maynard, D.] NHGRI, Bethesda, MD 20892 USA.
[Gochuico, B. R.] NHGRI, NIH, Bethesda, MD 20892 USA.
EM sel-chemaly@partners.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A1260
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838200250
ER
PT J
AU Cyphert, JM
Haile, AN
Sciurba, JD
Garantziotis, S
AF Cyphert, J. M.
Haile, A. N.
Sciurba, J. D.
Garantziotis, S.
TI Size Dependent Effects Of Hyaluronan On Airway Inflammation And
Remodeling
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Cyphert, J. M.; Sciurba, J. D.; Garantziotis, S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Haile, A. N.] Western Carolina Univ, Cullowhee, NC 28723 USA.
EM cyphertjm@mail.nih.gov
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A4016
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838203370
ER
PT J
AU Daniels, M
Wolf, W
Olivier, KN
Holland, SM
Zariwala, MA
Knowles, MR
AF Daniels, M.
Wolf, W.
Olivier, K. N.
Holland, S. M.
Zariwala, M. A.
Knowles, M. R.
TI Looking For Zebras, Finding An Okapi: Correcting A Rare Disease
Diagnosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Daniels, M.; Wolf, W.; Zariwala, M. A.; Knowles, M. R.] Univ N Carolina, Chapel Hill, NC USA.
[Olivier, K. N.] NIAID, Bethesda, MD 20892 USA.
[Holland, S. M.] NIH, Bethesda, MD 20892 USA.
EM leighanne_daniels@med.unc.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A6441
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838206240
ER
PT J
AU DiFrancesco, MF
Deo, R
Barr, RG
Bluemke, DA
Kronmal, R
Lima, J
Praestgaard, A
Tracy, RP
Shlipak, M
Kawut, SM
AF DiFrancesco, M. F.
Deo, R.
Barr, R. G.
Bluemke, D. A.
Kronmal, R.
Lima, J.
Praestgaard, A.
Tracy, R. P.
Shlipak, M.
Kawut, S. M.
TI Kidney Function And The Right Ventricle: The MESA - Right Ventricle
Study
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [DiFrancesco, M. F.; Deo, R.; Praestgaard, A.; Kawut, S. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Barr, R. G.] Columbia Univ, Med Ctr, New York, NY USA.
[Bluemke, D. A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Kronmal, R.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Lima, J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Tracy, R. P.] Univ Vermont, Coll Med, Colchester, VT USA.
[Shlipak, M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
EM mdifran@mail.med.upenn.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A4763
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838204255
ER
PT J
AU Dong, C
Luo, F
De Cabo, R
Lasky, JA
Sanchez, CG
AF Dong, C.
Luo, F.
De Cabo, R.
Lasky, J. A.
Sanchez, C. G.
TI The Involvement Of Circadian Clock Genes In Tumor Necrosis Factor Alpha
(tnf alpha) And Transforming Growth Factor-Beta1(tgf-beta 1)-Induced
Lung Injury And Fibrosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Dong, C.; Luo, F.; Lasky, J. A.; Sanchez, C. G.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[De Cabo, R.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A1948
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838201108
ER
PT J
AU Dugar, SP
Remy, KE
Shah, P
Martinez, A
AF Dugar, S. P.
Remy, K. E.
Shah, P.
Martinez, A.
TI Continuous In-House Intensivist Coverage Decreases Mortality, Ventilator
Free Hours, And Critical Care Length Of Stay In A Large, Community
Intensive Care Unit
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Dugar, S. P.; Shah, P.; Martinez, A.] St Agnes Hosp, Baltimore, MD USA.
[Remy, K. E.] NIH, Bethesda, MD 20892 USA.
EM siddharthdugarmd@gmail.com
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A4513
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838204007
ER
PT J
AU Elamin, EM
Miller, AC
Demirer, E
Shafik, Y
Kollipara, VN
AF Elamin, E. M.
Miller, A. C.
Demirer, E.
Shafik, Y.
Kollipara, V. N.
TI Vasopressors Use Following Single-Dose Etomidate In Critically Ill
Patients
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Elamin, E. M.] Univ Florida, Gainesville, FL USA.
[Miller, A. C.] NIH, Bethesda, MD 20892 USA.
[Demirer, E.] GATA Haydarpasa Training Hosp, Istanbul, Turkey.
[Shafik, Y.] Egyptian Mil Acad Hosp, Cairo, Egypt.
[Kollipara, V. N.] Texas Tech Univ, Amarillo, TX USA.
EM eelamin@haelth.usf.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A4550
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838204044
ER
PT J
AU Esmail, H
Lai, P
Graham, CM
Oni, T
Bangani, N
Warwick, JM
Said-Hartley, Q
Young, DB
Barry, CE
O'Garra, A
Wilkinson, RJ
AF Esmail, H.
Lai, P.
Graham, C. M.
Oni, T.
Bangani, N.
Warwick, J. M.
Said-Hartley, Q.
Young, D. B.
Barry, C. E.
O'Garra, A.
Wilkinson, R. J.
TI Characterisation Of A Whole Blood Transcriptional Signature Of
Subclinical Tuberculosis Identified By Fdg-Pet/ct In Asymptomatic Hiv-1
Infected Adults
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Esmail, H.; Oni, T.; Bangani, N.] Univ Cape Town, Cape Town, South Africa.
[Lai, P.; Graham, C. M.; Young, D. B.; O'Garra, A.] MRC Natl Inst Med Res, London, England.
[Warwick, J. M.] Univ Stellenbosch, Cape Town, South Africa.
[Said-Hartley, Q.] Groote Schurr Hosp, Cape Town, South Africa.
[Barry, C. E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Wilkinson, R. J.] Imperial Coll London, London, England.
EM h.esmail@imperial.ac.uk
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A6573
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838206371
ER
PT J
AU Faldetta, KF
Sheikh, VMW
Roby, GA
Prevots, DR
Sereti, I
Olivier, KN
AF Faldetta, K. F.
Sheikh, V. M. W.
Roby, G. A.
Prevots, D. R.
Sereti, I.
Olivier, K. N.
TI Clinical Characteristics Of Patients With Pulmonary Mac In A
Contemporary Hiv plus Iris Cohort
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Meeting Abstract
C1 [Faldetta, K. F.; Sheikh, V. M. W.; Roby, G. A.; Prevots, D. R.; Sereti, I.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Olivier, K. N.] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kimberly.faldetta@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PY 2014
VL 189
MA A1194
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA V45TF
UT WOS:000209838200189
ER
EF