FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Chen, KG
Mallon, BS
Johnson, KR
Hamilton, RS
Mckay, RDG
Robey, PG
AF Chen, Kevin G.
Mallon, Barbara S.
Johnson, Kory R.
Hamilton, Rebecca S.
McKay, Ronald D. G.
Robey, Pamela G.
TI Developmental insights from early mammalian embryos and core signaling
pathways that influence human pluripotent cell growth and
differentiation
SO STEM CELL RESEARCH
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; FEEDER-FREE CONDITIONS; STEM-CELLS;
SELF-RENEWAL; IN-VITRO; GSK-3-SPECIFIC INHIBITOR; CULTURE; MAINTENANCE;
SUSPENSION; MOUSE
AB Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. Published by Elsevier B.V.
C1 [Chen, Kevin G.; Mallon, Barbara S.; Hamilton, Rebecca S.] NINDS, NIH Stem Cell Unit, NIH, Bethesda, MD 20892 USA.
[Johnson, Kory R.] NINDS, Informat Technol & Bioinformat Program, NIH, Bethesda, MD 20892 USA.
[McKay, Ronald D. G.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Chen, KG (reprint author), NINDS, NIH Stem Cell Unit, NIH, 37 Convent Dr,Room 1000, Bethesda, MD 20892 USA.
EM cheng@mail.nih.gov
RI Chen, Kevin/D-6769-2011; Robey, Pamela/H-1429-2011
OI Chen, Kevin/0000-0003-2983-6330; Robey, Pamela/0000-0002-5316-5576
FU National Institutes of Health (NIH) at the National Institute of
Neurological Disorders and Stroke
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH) at the National Institute of
Neurological Disorders and Stroke. We would like to thank Dr. Peter
Zandstra for his comments and suggestions.
NR 66
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD MAY
PY 2014
VL 12
IS 3
BP 610
EP 621
DI 10.1016/j.scr.2014.02.002
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AP7VX
UT WOS:000342286900002
PM 24603366
ER
PT J
AU Vogel, J
Gottesman, S
Belasco, J
Narberhaus, F
AF Vogel, Joerg
Gottesman, Susan
Belasco, Joel
Narberhaus, Franz
TI Regulating with RNA in Bacteria 2013
SO RNA BIOLOGY
LA English
DT Article
DE small RNA; Hfq; RNA stability; RNA-seq CRISPR; Cascade;
ribonucleoprotein complex; bioinformatics
ID SP PCC 6803; MESSENGER-RNA; BACILLUS-SUBTILIS; ESCHERICHIA-COLI;
TRANSLATION INITIATION; CHAPERONE HFQ; HELICOBACTER-PYLORI; BIOFILM
FORMATION; SOLUBLE-RNA; PROTEIN
AB On June 4-8, 2013, the 3rd Conference on Regulation with RNA in Bacteria took place in Wurzburg, Germany. Following two earlier meetings in Berlin and San Juan, this conference has established itself as the primary bi-annual meeting for everyone interested in RNA-based regulations in prokaryotes. The 2013 meeting was organized by Joel Belasco, Susan Gottesman, Franz Narberhaus, and Jorg Vogel. Close to 300 participants from more than 27 countries in Europe, North America, and Asia enjoyed four days of talks and posters on many experimental and biocomputational aspects of prokaryotic RNA biology.
C1 [Vogel, Joerg] Univ Wurzburg, RNA Biol Grp, IMIB, D-97070 Wurzburg, Germany.
[Gottesman, Susan] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
[Belasco, Joel] NYU, Sch Med, Kimmel Ctr Biol & Med, Skirball Inst, New York, NY USA.
[Belasco, Joel] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA.
[Narberhaus, Franz] Ruhr Univ Bochum, Bochum, Germany.
RP Vogel, J (reprint author), Univ Wurzburg, RNA Biol Grp, IMIB, D-97070 Wurzburg, Germany.
EM joerg.vogel@uni-wuerzburg.de; gottesms@helix.nih.gov;
Joel.Belasco@med.nyu.edu; Franz.Narberhaus@ruhr-uni-bochum.de
RI Vogel, Jorg/D-5574-2011
OI Vogel, Jorg/0000-0003-2220-1404
FU German Research Foundation (DFG) [NA 240/6-2]
FX This conference was supported by the German Research Foundation (DFG,
grant NA 240/6-2).
NR 81
TC 1
Z9 1
U1 2
U2 14
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1547-6286
EI 1555-8584
J9 RNA BIOL
JI RNA Biol.
PD MAY
PY 2014
VL 11
IS 5
BP 403
EP 412
DI 10.4161/rna.29533
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AO7FI
UT WOS:000341517200001
PM 24922515
ER
PT J
AU Leroy, G
Chen, HC
Rindflesch, TC
AF Leroy, Gondy
Chen, Hsinchun
Rindflesch, Thomas C.
TI Smart and Connected Health INTRODUCTION
SO IEEE INTELLIGENT SYSTEMS
LA English
DT Editorial Material
C1 [Leroy, Gondy] Univ Arizona, Dept Management Informat Syst MIS, Tucson, AZ 85721 USA.
[Chen, Hsinchun] Univ Arizona, Tucson, AZ 85721 USA.
[Rindflesch, Thomas C.] Natl Lib Med, Lister Hill Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Leroy, G (reprint author), Univ Arizona, Dept Management Informat Syst MIS, Tucson, AZ 85721 USA.
EM gondyleroy@email.arizona.edu; hchen@eller.arizona.edu; tcr@nlm.nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 2
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1541-1672
EI 1941-1294
J9 IEEE INTELL SYST
JI IEEE Intell. Syst.
PD MAY-JUN
PY 2014
VL 29
IS 3
BP 2
EP 5
PG 4
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA AO8AX
UT WOS:000341575700001
ER
PT J
AU Bowman, EA
Kelly, WG
AF Bowman, Elizabeth A.
Kelly, William G.
TI RNA Polymerase II transcription elongation and Pol II CTD Ser2
phosphorylation A tail of two kinases
SO NUCLEUS
LA English
DT Review
DE transcription; RNA Polymerase II; Serine 2; Bur1; Ctk1; Cdk9; Cdk12;
P-TEFb; elongation; C. elegans
ID CYCLIN-DEPENDENT KINASE; CARBOXY-TERMINAL DOMAIN; EMBRYONIC STEM-CELLS;
TEFB-MEDIATED PHOSPHORYLATION; BROMODOMAIN PROTEIN BRD4; P-TEFB;
IN-VIVO; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; REPEAT DOMAIN
AB The transition between initiation and productive elongation during RNA Polymerase II (Pol II) transcription is a well-appreciated point of regulation across many eukaryotes. Elongating Pol II is modified by phosphorylation of serine 2 (Ser2) on its carboxy terminal domain (CTD) by two kinases, Bur1/Ctk1 in yeast and Cdk9/Cdk12 in metazoans. Here, we discuss the roles and regulation of these kinases and their relationship to Pol II elongation control, and focus on recent data from work in C. elegans that point out gaps in our current understand of transcription elongation.
C1 [Bowman, Elizabeth A.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Kelly, William G.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
RP Bowman, EA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM bowmanea@niehs.nih.gov
FU NIGMS NIH HHS [R01 GM101040]
NR 169
TC 14
Z9 14
U1 1
U2 11
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1949-1034
EI 1949-1042
J9 NUCLEUS-PHILA
JI Nucleus
PD MAY-JUN
PY 2014
VL 5
IS 3
BP 224
EP 236
DI 10.4161/nucl.29347
PG 13
WC Cell Biology
SC Cell Biology
GA AO8YK
UT WOS:000341641600005
PM 24879308
ER
PT J
AU Kouzine, F
Levens, D
Baranello, L
AF Kouzine, Fedor
Levens, David
Baranello, Laura
TI DNA topology and transcription
SO NUCLEUS-AUSTIN
LA English
DT Article
DE DNA topoisomerases; DNA topological domain; DNA topology; torsional
stress; transcription
ID RNA-POLYMERASE-II; NUCLEOSOME REPEAT LENGTH; C-MYC EXPRESSION;
GENE-EXPRESSION; HISTONE ACETYLATION; CHROMATIN-STRUCTURE; IN-VIVO;
REGULATED TRANSCRIPTION; DIVERGENT TRANSCRIPTION; ANTISENSE
TRANSCRIPTION
AB Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions.
C1 [Kouzine, Fedor; Levens, David; Baranello, Laura] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Baranello, L (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA.
EM baranellolf@mail.nih.gov
RI Levens, David/C-9216-2009
OI Levens, David/0000-0002-7616-922X
NR 93
TC 7
Z9 7
U1 2
U2 13
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1949-1034
EI 1949-1042
J9 NUCLEUS-AUSTIN
JI Nucleus-Austin
PD MAY-JUN
PY 2014
VL 5
IS 3
BP 195
EP 202
DI 10.4161/nucl.28909
PG 8
WC Cell Biology
SC Cell Biology
GA AO8YK
UT WOS:000341641600001
PM 24755522
ER
PT J
AU Sugiyama, H
Misumi, M
Kishikawa, M
Iseki, M
Yonehara, S
Hayashi, T
Soda, M
Tokuoka, S
Shimizu, Y
Sakata, R
Grant, EJ
Kasagi, F
Mabuchi, K
Suyama, A
Ozasa, K
AF Sugiyama, Hiromi
Misumi, Munechika
Kishikawa, Masao
Iseki, Masachika
Yonehara, Shuji
Hayashi, Tomayoshi
Soda, Midori
Tokuoka, Shoji
Shimizu, Yukiko
Sakata, Ritsu
Grant, Eric J.
Kasagi, Fumiyoshi
Mabuchi, Kiyohiko
Suyama, Akihiko
Ozasa, Kotaro
TI Skin Cancer Incidence among Atomic Bomb Survivors from 1958 to 1996
SO RADIATION RESEARCH
LA English
DT Article
ID BASAL-CELL CARCINOMA; RADIATION-THERAPY; SQUAMOUS-CELL; SOLID CANCER;
RISK; MORTALITY; IRRADIATION; RINGWORM; EXPOSURE; SCALP
AB The radiation risk of skin cancer by histological types has been evaluated in the atomic bomb survivors. We examined 80,158 of the 120,321 cohort members who had their radiation dose estimated by the latest dosimetry system (DS02). Potential skin tumors diagnosed from 1958 to 1996 were reviewed by a panel of pathologists, and radiation risk of the first primary skin cancer was analyzed by histological types using a Poisson regression model. A significant excess relative risk (ERR) of basal cell carcinoma (BCC) (n = 123) was estimated at 1 Gy (0.74, 95% confidence interval (CI): 0.26, 1.6) for those age 30 at exposure and age 70 at observation based on a linear-threshold model with a threshold dose of 0.63 Gy (95% CI: 0.32, 0.89) and a slope of 2.0 (95% CI: 0.69, 4.3). The estimated risks were 15, 5.7, 1.3 and 0.9 for age at exposure of 0-9, 10-19, 20-39, over 40 years, respectively, and the risk increased 11% with each one-year decrease in age at exposure. The ERR for squamous cell carcinoma (SCC) in situ (n 64) using a linear model was estimated as 0.71 (95% CI: 0.063, 1.9). However, there were no significant dose responses for malignant melanoma (n = 10), SCC (n = 114), Paget disease (n = 10) or other skin cancers (n = 15). The significant linear radiation risk for BCC with a threshold at 0.63 Gy suggested that the basal cells of the epidermis had a threshold sensitivity to ionizing radiation, especially for young persons at the time of exposure. (C) 2014 by Radiation Research Society
C1 [Sugiyama, Hiromi; Soda, Midori; Tokuoka, Shoji; Shimizu, Yukiko; Sakata, Ritsu; Grant, Eric J.; Ozasa, Kotaro] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan.
[Sugiyama, Hiromi; Soda, Midori; Tokuoka, Shoji; Shimizu, Yukiko; Sakata, Ritsu; Grant, Eric J.; Ozasa, Kotaro] Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki, Japan.
[Misumi, Munechika] Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan.
[Kishikawa, Masao] Nagasaki Diagnost Pathol Clin, Nagasaki, Japan.
[Iseki, Masachika] Sasebo Kyosai Hosp, Dept Pathol & Lab Med, Nagasaki, Japan.
[Yonehara, Shuji] Welf Assoc Onomichi Gen Hosp, Dept Pathol, Hiroshima, Japan.
[Yonehara, Shuji] Welf Assoc Onomichi Gen Hosp, Res Lab, Hiroshima, Japan.
[Hayashi, Tomayoshi] Nagasaki Univ Hosp, Dept Pathol, Nagasaki, Japan.
[Kasagi, Fumiyoshi] Radiat Effects Assoc, Inst Radiat Epidemiol, Tokyo, Japan.
[Mabuchi, Kiyohiko] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Suyama, Akihiko] Prefecture Osaka Saiseikai Izuo Hosp, Dept Gen Internal Med, Osaka, Japan.
RP Sugiyama, H (reprint author), Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, 5-2 Hijiyama Pk, Hiroshima, Japan.
EM sugi@rerf.or.jp
FU Japanese Ministry of Health, Labour and Welfare (MHLW); U.S. Department
of Energy (DOE); DOE [DE-HS0000031]; RERF Research Protocol(s) RP [2-91,
2-02]; U.S. National Cancer Institute (NCI) [N01-CP-31012]
FX We would like to thank the Hiroshima City Cancer Registry, the Hiroshima
Prefecture Tumor Registry and the Nagasaki Prefecture Cancer Registry
for approval to use the data, and also thank the staff of the registries
for their efforts. The assistance of Ms. Sachiyo Funamoto and staff of
the pathology laboratory are gratefully acknowledged. Special thanks are
expressed to the late Dr. Elaine Ron for her advice. This paper is
dedicated to Dr. Shoji Tokuoka, a key leader and pathologist of the
site-specific cancer study program in A-bomb survivors for 25 years at
RERF. His untimely death during final preparation of this paper, took
from us a dedicated researcher. The Radiation Effects Research
Foundation (RERF), Hiroshima and Nagasaki, Japan is a private, nonprofit
foundation funded by the Japanese Ministry of Health, Labour and Welfare
(MHLW) and the U.S. Department of Energy (DOE), the latter in part
through DOE Award DE-HS0000031 to the National Academy of Sciences that
supported EJG. This publication was supported by RERF Research
Protocol(s) RP 2-91 and 2-02, and with additional support from U.S.
National Cancer Institute (NCI) contract number N01-CP-31012. The views
of the authors do not necessarily reflect those of the two governments.
NR 32
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U1 1
U2 5
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD MAY
PY 2014
VL 181
IS 5
BP 531
EP 539
DI 10.1667/RR13494.1
PG 9
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA AO4KZ
UT WOS:000341308100010
PM 24754560
ER
PT J
AU Jha, A
Brailoiu, E
Muallem, S
AF Jha, Archana
Brailoiu, Eugen
Muallem, Shmuel
TI How does NAADP release lysosomal Ca2+?
SO CHANNELS
LA English
DT Editorial Material
ID 2-PORE CHANNELS; ION CHANNELS
C1 [Jha, Archana; Muallem, Shmuel] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Brailoiu, Eugen] Temple Univ, Dept Pharmacol, Sch Med, Philadelphia, PA 19122 USA.
RP Brailoiu, E (reprint author), Temple Univ, Dept Pharmacol, Sch Med, Philadelphia, PA 19122 USA.
EM ebrailoiu@temple.edu; shmuel.muallem@nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6950
EI 1933-6969
J9 CHANNELS
JI Channels
PD MAY-JUN
PY 2014
VL 8
IS 3
DI 10.4161/chan.28995
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AN6QU
UT WOS:000340722000005
ER
PT J
AU Park, JC
Citrin, DE
Agarwal, PK
Apolo, AB
AF Park, Jong Chul
Citrin, Deborah E.
Agarwal, Piyush K.
Apolo, Andrea B.
TI Multimodal management of muscle-invasive bladder cancer
SO CURRENT PROBLEMS IN CANCER
LA English
DT Article
ID TRANSITIONAL-CELL-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED
PHASE-III; EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; METASTATIC
UROTHELIAL CANCER; SELECTIVE ORGAN PRESERVATION; CHEMOTHERAPY FOLLOWING
CYSTECTOMY; UNSUSPECTED PULMONARY-EMBOLISM; GEMCITABINE PLUS CISPLATIN;
COMBINED-MODALITY THERAPY
C1 [Park, Jong Chul] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA.
[Citrin, Deborah E.] NCI, Radiat Oncol Branch, Sect Translat Radiat Oncol, Bethesda, MD 20892 USA.
[Agarwal, Piyush K.] NCI, Urol Oncol Branch, Bladder Canc Sect, Bethesda, MD 20892 USA.
[Apolo, Andrea B.] NCI, Bladder Canc Sect, Genitourinary Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Park, JC (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA.
FU Intramural NIH HHS [ZIA BC011351-04]
NR 196
TC 4
Z9 4
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0147-0272
EI 1535-6345
J9 CURR PROB CANCER
JI Curr. Probl. Cancer
PD MAY-JUN
PY 2014
VL 38
IS 3
BP 80
EP 108
DI 10.1016/j.currproblcancer.2014.06.001
PG 29
WC Oncology
SC Oncology
GA AN6UR
UT WOS:000340734400001
PM 25087173
ER
PT J
AU Putluri, N
Maity, S
Kommangani, R
Creighton, CJ
Putluri, V
Chen, FJ
Nanda, S
Bhowmik, SK
Terunuma, A
Dorsey, T
Nardone, A
Fu, XY
Shaw, C
Sarkar, TR
Schiff, R
Lydon, JP
O'Malley, BW
Ambs, S
Das, GM
Michailidis, G
Sreekumar, A
AF Putluri, Nagireddy
Maity, Suman
Kommangani, Ramakrishna
Creighton, Chad J.
Putluri, Vasanta
Chen, Fengju
Nanda, Sarmishta
Bhowmik, Salil Kumar
Terunuma, Atsushi
Dorsey, Tiffany
Nardone, Agostina
Fu, Xiaoyong
Shaw, Chad
Sarkar, Tapasree Roy
Schiff, Rachel
Lydon, John P.
O'Malley, Bert W.
Ambs, Stefan
Das, Gokul M.
Michailidis, George
Sreekumar, Arun
TI Pathway-Centric Integrative Analysis Identifies RRM2 as a Prognostic
Marker in Breast Cancer Associated with Poor Survival and Tamoxifen
Resistance
SO NEOPLASIA
LA English
DT Article
ID SET ENRICHMENT ANALYSIS; LYMPH-NODE METASTASIS; PROFILING PREDICTS;
MOLECULAR SUBTYPES; MASS-SPECTROMETRY; CELL-LINES; ESTROGEN;
METABOLOMICS; MUTATIONS; THERAPY
AB Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2-enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa.
C1 [Putluri, Nagireddy; Maity, Suman; Kommangani, Ramakrishna; Putluri, Vasanta; Bhowmik, Salil Kumar; Schiff, Rachel; Lydon, John P.; O'Malley, Bert W.; Sreekumar, Arun] Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA.
[Putluri, Nagireddy; Maity, Suman; Putluri, Vasanta; Bhowmik, Salil Kumar; Sreekumar, Arun] Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Houston, TX 77030 USA.
[Putluri, Nagireddy; Maity, Suman; Putluri, Vasanta; Bhowmik, Salil Kumar; O'Malley, Bert W.; Sreekumar, Arun] Baylor Coll Med, Alkek Ctr Mol Discovery, Houston, TX 77030 USA.
[Creighton, Chad J.; Chen, Fengju; Shaw, Chad; Schiff, Rachel] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Creighton, Chad J.; Chen, Fengju; Shaw, Chad; Schiff, Rachel; O'Malley, Bert W.; Sreekumar, Arun] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Nardone, Agostina; Fu, Xiaoyong; Schiff, Rachel] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Terunuma, Atsushi; Dorsey, Tiffany; Ambs, Stefan] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sarkar, Tapasree Roy] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA.
[Das, Gokul M.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA.
[Michailidis, George] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
RP Sreekumar, A (reprint author), Baylor Coll Med, Verna & Marrs Mclean Dept Biochem, Dept Mol & Cell Biol, Houston, TX 77030 USA.
EM gmichail@umich.edu; arun.sreekumar@bcm.edu
FU Susan Komen Foundation [PG 1221410]; National Institute of Health (NIH)
[U01 CA167234, HD-07857, NSFDMS-1161759]; National Science Foundation
(NSF) [DMS-12-28164, DMS-11617838]; Cancer Prevention Research Institute
of Texas [RP120092]; Alkek Center for Molecular Discovery; Breast Cancer
Research Foundation; Dan L Duncan Cancer Center [NCI-P30CA016056-32];
Roswell Park Cancer Institute [PG 1221410]; NCI [RP120092, P30
CA125123]; [NCI P30 CA125123]
FX This research was supported by the following grant support: Susan Komen
Foundation (to A.S., N.P., R.S., and B.W.O.), PG 1221410 (to R.S.),
National Institute of Health (NIH) U01 CA167234 (to A.S., N.P., and
G.M.), NSFDMS-1161759 (to A.S.and G.M.), National Science Foundation
(NSF) DMS-12-28164 (to G.M.) and National Science Foundation (NSF)
DMS-11617838 (to G.M.), NCI P30 CA125123 (to C.J.C. and F.C.), RP120092
(to A.S. and N.P.), National Institute of Health (NIH) HD-07857 (to
B.W.O.), RP120092 from Cancer Prevention Research Institute of Texas (to
A.S.and N.P.), funds from the Alkek Center for Molecular Discovery (to
A.S.), Breast Cancer Research Foundation (to R.S.), Dan L Duncan Cancer
Center, NCI-P30CA016056-32 for Pathology Resource Network (PRN), and PG
1221410 (to R.S and B.W.O), Roswell Park Cancer Institute.
NR 73
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U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1522-8002
EI 1476-5586
J9 NEOPLASIA
JI Neoplasia
PD MAY
PY 2014
VL 16
IS 5
BP 390
EP 402
DI 10.1016/j.neo.2014.05.007
PG 13
WC Oncology
SC Oncology
GA AN4JD
UT WOS:000340552900002
PM 25016594
ER
PT J
AU Cimms, TA
Howard, K
Portalupi, S
Saretsky, TL
Hoffmann, S
Crawley, JA
Lorens, L
Powers, JH
AF Cimms, T. A.
Howard, K.
Portalupi, S.
Saretsky, T. L.
Hoffmann, S.
Crawley, J. A.
Lorens, L.
Powers, J. H.
CA FNIH Biomarkers Consortium CABP
TI SIGNS, SYMPTOMS, AND EXISTING PATIENT REPORTED OUTCOME (PRO) MEASURES IN
COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP): A COMPREHENSIVE
LITERATURE REVIEW
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Cimms, T. A.; Crawley, J. A.] AstraZeneca, Gaithersburg, MD USA.
[Howard, K.; Portalupi, S.; Saretsky, T. L.] Oxford Outcomes, San Francisco, CA USA.
[Hoffmann, S.] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Lorens, L.] Cerexa Inc, Oakland, CA USA.
[Powers, J. H.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2014
VL 17
IS 3
MA PIN84
BP A279
EP A279
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA AO1OG
UT WOS:000341082001665
ER
PT J
AU Howard, K
Portalupi, S
Hoffmann, S
Crawley, JA
Lorens, L
Cimms, TA
Powers, JH
AF Howard, K.
Portalupi, S.
Hoffmann, S.
Crawley, J. A.
Lorens, L.
Cimms, T. A.
Powers, J. H.
CA FNIH Biomarkers Consortium CABP
TI DEVELOPMENT OF A NEW PATIENT REPORTED OUTCOME (PRO) MEASURE FOR
COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA (CABP)
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Howard, K.; Portalupi, S.] Oxford Outcomes, San Francisco, CA USA.
[Hoffmann, S.] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Crawley, J. A.; Cimms, T. A.] AstraZeneca, Gaithersburg, MD USA.
[Lorens, L.] Cerexa Inc, Oakland, CA USA.
[Powers, J. H.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2014
VL 17
IS 3
MA PIN85
BP A280
EP A280
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA AO1OG
UT WOS:000341082001666
ER
PT J
AU Majercak, K
Nghiem, E
Byrne, C
Muti, P
Barba, M
Lavigne, J
Faupel-Badger, J
Teter, B
Fuhrman, B
AF Majercak, K.
Nghiem, E.
Byrne, C.
Muti, P.
Barba, M.
Lavigne, J.
Faupel-Badger, J.
Teter, B.
Fuhrman, B.
TI MAMMOGRAPHIC DENSITY IN ASSOCIATION WITH SMOKING STATUS AND SMOKING
HISTORIES IN A SAMPLE OF POSTMENOPAUSAL WOMEN: RESULTS FROM A
CROSS-SECTIONAL STUDY
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Majercak, K.; Fuhrman, B.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Nghiem, E.] Univ Maryland, College Pk, MD 20742 USA.
[Byrne, C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Muti, P.] McMaster Univ, Hamilton, ON, Canada.
[Barba, M.] Italian Natl Canc Inst, Rome, Italy.
[Lavigne, J.; Faupel-Badger, J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Teter, B.] SUNY Buffalo, Buffalo, NY 14260 USA.
RI Byrne, Celia/K-2964-2015
OI Byrne, Celia/0000-0001-8289-4252
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2014
VL 17
IS 3
MA PCN26
BP A72
EP A72
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA AO1OG
UT WOS:000341082000391
ER
PT J
AU Powers, JH
Portalupi, S
Devine, J
Saretsky, TL
Hoffmann, S
Crawley, J
Lorens, L
Cimms, TA
Howard, K
AF Powers, J. H.
Portalupi, S.
Devine, J.
Saretsky, T. L.
Hoffmann, S.
Crawley, J.
Lorens, L.
Cimms, T. A.
Howard, K.
CA FNIH Biomarkers Consortium CABP
TI ACUTE BACTERIAL SKIN AND SKIN STRUCTURE INFECTION (ABSSI): DEVELOPMENT
OF A NEW PATIENT REPORTED OUTCOME (PRO)
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Powers, J. H.] NIAID, NIH, Bethesda, MD 20892 USA.
[Portalupi, S.; Devine, J.; Saretsky, T. L.; Howard, K.] Oxford Outcomes, San Francisco, CA USA.
[Hoffmann, S.] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Crawley, J.; Cimms, T. A.] AstraZeneca, Gaithersburg, MD USA.
[Lorens, L.] Cerexa Inc, Oakland, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2014
VL 17
IS 3
MA PSS31
BP A288
EP A288
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA AO1OG
UT WOS:000341082001714
ER
PT J
AU Shi, W
Greco, G
Gelijns, A
Blackstone, E
Moskowitz, A
O'Gara,
Jeffries, N
Bagiella, E
AF Shi, W.
Greco, G.
Gelijns, A.
Blackstone, E.
Moskowitz, A.
O'Gara
Jeffries, N.
Bagiella, E.
TI ESTIMATING THE COST OF HEALTH CARE ASSOCIATED INFECTIONS CONTROLLING FOR
BOTH PATIENT VARIABILITY AND TIME-DEPENDENT BIAS
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Shi, W.; Greco, G.; Gelijns, A.; Moskowitz, A.; Bagiella, E.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Blackstone, E.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[O'Gara] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Jeffries, N.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD MAY
PY 2014
VL 17
IS 3
MA PRM30
BP A186
EP A186
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA AO1OG
UT WOS:000341082001147
ER
PT J
AU McAuley, PA
Chen, HY
Lee, DC
Artero, EG
Bluemke, DA
Burke, GL
AF McAuley, Paul A.
Chen, Haiying
Lee, Duck-chul
Artero, Enrique Garcia
Bluemke, David A.
Burke, Gregory L.
TI Physical Activity, Measures of Obesity, and Cardiometabolic Risk: The
Multi-Ethnic Study of Atherosclerosis (MESA)
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE cardiovascular disease; diabetes; ethnicity; obesity
ID CARDIOVASCULAR-DISEASE RISK; BODY-MASS INDEX; LOW CARDIORESPIRATORY
FITNESS; ALL-CAUSE MORTALITY; WEIGHT-LOSS; INSULIN-RESISTANCE; METABOLIC
SYNDROME; MEN; HEALTH; WOMEN
AB Background: The influence of higher physical activity on the relationship between adiposity and cardiometabolic risk is not completely understood. Methods: Between 2000-2002, data were collected on 6795 Multi-Ethnic Study of Atherosclerosis (MESA) participants. Self-reported intentional physical activity in the lowest quartile (0-105 MET-minutes/week) was categorized as inactive and the upper three quartiles (123-37,260 MET-minutes/week) as active. Associations of body mass index (BMI) and waist circumference categories, stratified by physical activity status (inactive or active) with cardiometabolic risk factors (dyslipidemia, hypertension, upper quartile of homeostasis model assessment of insulin resistance [HOMA-IR] for population, and impaired fasting glucose or diabetes) were assessed using logistic regression analysis adjusting for age, gender, race/ethnicity, and current smoking. Results: Among obese participants, those who were physically active had reduced odds of insulin resistance (47% lower; P < .001) and impaired fasting glucose/diabetes (23% lower; P = .04). These associations were weaker for central obesity. However, among participants with a normal waist circumference, those who were inactive were 63% more likely to have insulin resistance (OR [95% CI] 1.63 [1.24-2.15]) compared with the active reference group. Conclusions: Physical activity was inversely related to the cardiometabolic risk associated with obesity and central obesity.
C1 [McAuley, Paul A.] Winston Salem State Univ, Dept Hlth Phys Educ & Sport Sci, Winston Salem, NC 27110 USA.
[Chen, Haiying] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA.
[Lee, Duck-chul] Iowa State Univ, Dept Kinesiol, Ames, IA USA.
[Artero, Enrique Garcia] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA.
[Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Burke, Gregory L.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC USA.
RP McAuley, PA (reprint author), Winston Salem State Univ, Dept Hlth Phys Educ & Sport Sci, Winston Salem, NC 27110 USA.
RI Artero, Enrique G./L-8628-2014;
OI Artero, Enrique G./0000-0002-2618-6128; Bluemke,
David/0000-0002-8323-8086
FU NCRR NIH HHS [M01-RR07122, M01 RR007122]; NHLBI NIH HHS [N01 HC095165,
N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163,
N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95169, N01HC95159,
N01HC95166, N01HC95169]
NR 31
TC 4
Z9 4
U1 1
U2 9
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD MAY
PY 2014
VL 11
IS 4
BP 831
EP 837
DI 10.1123/jpah.2012-0326
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AM6OM
UT WOS:000339984500021
PM 23676525
ER
PT J
AU Rosentul, DC
Plantinga, TS
Farcas, M
Oosting, M
Hamza, OJM
Scott, WK
Alexander, BD
Yang, JC
Laird, GM
Joosten, LAB
van der Meer, JWM
Perfect, JR
Kullberg, BJ
van der Ven, AJAM
Johnson, MD
Netea, MG
AF Rosentul, Diana C.
Plantinga, Theo S.
Farcas, Marius
Oosting, Marije
Hamza, Omar J. M.
Scott, William K.
Alexander, Barbara D.
Yang, John C.
Laird, Gregory M.
Joosten, Leo A. B.
van der Meer, Jos W. M.
Perfect, John R.
Kullberg, Bart-Jan
van der Ven, Andre J. A. M.
Johnson, Melissa D.
Netea, Mihai G.
TI Role of autophagy genetic variants for the risk of Candida infections
SO MEDICAL MYCOLOGY
LA English
DT Article
DE HIV; Candida albicans; candidemia; autophagy; oropharyngeal candidiasis;
genetic association study
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; GENOME-WIDE ASSOCIATION;
CROHNS-DISEASE; FUNGAL-INFECTIONS; HUMAN DECTIN-1; SUSCEPTIBILITY;
POLYMORPHISM; PREVALENCE; LOCI; IRGM
AB Candida albicans can cause candidemia in neutropenic and critically ill patients and oropharyngeal candidiasis in human immunodeficiency virus (HIV)-positive patients with low CD4(+) counts. Because all patients at risk do not develop Candida infections, it is possible that a patient's genetic background might play a role in his or her susceptibility to infection. Autophagy mediates pathogen clearance and modulation of inflammation. Our aim was to assess the effect of genetic variations in the ATG16L1 and IRGM autophagy genes on the susceptibility of patients with candidemia and oropharyngeal candidiasis. We assessed genetic variations in the ATG16L1 and IRGM genes in a cohort of candidemia patients of both African and European origin. In addition, we evaluated the effect of these polymorphisms on the susceptibility to oropharyngeal candidiasis of an HIV-positive cohort from Tanzania. Functional studies have been performed to assess the effect of the ATG16L1 and IRGM genetic variants on both in vitro and in vivo cytokine production. The results indicate that ATG16L1 variants modulate production of tumor necrosis factor-alpha, but not other cytokines, while no effects were seen in the presence of IRGM polymorphisms. In addition, no significant associations between the single-nucleotide polymorphisms in the ATG16L1 and IRGM genetic variants and the incidence of candidemia or oropharyngeal candidiasis were identified.
Despite moderate effects on the modulation of proinflammatory cytokine production, genetic variation in the autophagy genes ATG16L1 and IRGM has a minor impact on the susceptibility to both mucosal and systemic Candida infections.
C1 [Rosentul, Diana C.; Plantinga, Theo S.; Farcas, Marius; Oosting, Marije; Joosten, Leo A. B.; van der Meer, Jos W. M.; Kullberg, Bart-Jan; van der Ven, Andre J. A. M.; Netea, Mihai G.] Radboud Univ Nijmegen Med Ctr, Dept Med, Nijmegen, Netherlands.
[Rosentul, Diana C.; Plantinga, Theo S.; Farcas, Marius; Oosting, Marije; Joosten, Leo A. B.; van der Meer, Jos W. M.; Kullberg, Bart-Jan; van der Ven, Andre J. A. M.; Netea, Mihai G.] Radboud Univ Nijmegen Med Ctr, Nijmegen Inst Infect Inflammat & Immun, Nijmegen, Netherlands.
[Farcas, Marius] Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca, Romania.
[Hamza, Omar J. M.] Muhimbili Univ Coll Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Scott, William K.] Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.
[Scott, William K.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
[Alexander, Barbara D.; Laird, Gregory M.; Perfect, John R.; Johnson, Melissa D.] Duke Univ Med Ctr, Div Infect Dis & Int Hlth, Durham, NC USA.
[Yang, John C.] Natl Jewish Hlth, Denver, CO USA.
NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Johnson, Melissa D.] Campbell Univ Sch Pharm, Dept Clin Res, Buies Creek, NC USA.
RP Netea, MG (reprint author), Radboud Univ Nijmegen Med Ctr, Dept Med 463, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM mihai.netea@radboudumc.nl
RI Andrade, Hugo/M-6631-2013; Plantinga, Theo/A-6895-2015; Joosten,
Leo/H-3138-2015; Ven, A.J.A.M./H-8102-2014; Kullberg, Bart
Jan/C-8520-2013; Netea, Mihai/N-5155-2014; van der Meer,
Jos/C-8521-2013; Oosting, Marije/H-7437-2015;
OI Andrade, Hugo/0000-0001-6781-6125; van der Meer,
Jos/0000-0001-5120-3690; Johnson, Melissa/0000-0002-6606-9460
FU European Commission through the FINSysB Marie Curie Initial Training
Network [PITN-GA-2008-214004]; Veni grant from the Netherlands
Organization for Scientific Research; European Research Council from the
European Research Council [310372]; National Institutes of Health
[AI-51537, AI-73896]
FX D.C.R. received funding from the European Commission through the FINSysB
Marie Curie Initial Training Network (PITN-GA-2008-214004). T. S. P. was
supported by a Veni grant from the Netherlands Organization for
Scientific Research. This study was partially supported by an European
Research Council Consolidator Grant (nr. 310372) from the European
Research Council to M.G.N. and by National Institutes of Health grants
AI-51537 to M.D.J. and AI-73896 to J.R.P. All authors had full access to
all study data and take responsibility for data integrity data and
accuracy of data analysis.
NR 37
TC 7
Z9 7
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1369-3786
EI 1460-2709
J9 MED MYCOL
JI Med. Mycol.
PD MAY
PY 2014
VL 52
IS 4
BP 333
EP 341
DI 10.1093/mmy/myt035
PG 9
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA AM5PX
UT WOS:000339913600001
PM 24713404
ER
PT J
AU Bartlett, EK
Kammula, US
AF Bartlett, Edmund K.
Kammula, Udai S.
TI Location, location, location The relationship of anatomic site, antigen
expression, and T-cell infiltration in human melanoma metastases
SO ONCOIMMUNOLOGY
LA English
DT Editorial Material
DE melanoma; metastases; site-specific expression; differentiation antigen;
immunoediting
ID HETEROGENEITY
AB Metastatic cell heterogeneity presents a significant obstacle to the development of targeted molecular and immunotherapeutics. Profiling of melanocyte differentiation antigens has revealed a nonstochastic, site-specific pattern of expression in metastases that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral sites. Site-specific antigen heterogeneity, thus, is an important confounding factor to consider when assessing the potential efficacy of antigen-specific therapies.
C1 [Bartlett, Edmund K.; Kammula, Udai S.] NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Kammula, US (reprint author), NCI, Ctr Canc Res, Surg Branch, NIH, Bethesda, MD 20892 USA.
EM udai_kammula@nih.gov
OI Bartlett, Edmund/0000-0002-0923-153X
NR 10
TC 0
Z9 0
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2162-4011
EI 2162-402X
J9 ONCOIMMUNOLOGY
JI OncoImmunology
PD MAY
PY 2014
VL 3
IS 5
AR e28963
DI 10.4161/onci.28963
PG 2
WC Oncology; Immunology
SC Oncology; Immunology
GA AM6EP
UT WOS:000339956200016
ER
PT J
AU Ohnuki, H
Tosato, G
AF Ohnuki, Hidetaka
Tosato, Giovanna
TI Notch and TGF beta Functional partners facilitating tumor progression
SO ONCOIMMUNOLOGY
LA English
DT Editorial Material
DE Notch; Tgf beta; tumor-infiltrating myeloid cells; head and neck tumors;
tumor microenvironment; tumor progression
ID SIGNALING PATHWAYS; CANCER; CELLS
AB Cell signals integral to the tumor microenvironment influence cancer progression. Tumor-associated myeloid cells secrete pro-tumorigenic agents including, but not limited to, the potent cytokine transforming growth factor beta (TGF beta). We have discovered a network of extrinsic signals including delta-like 4 (Dll4), Notch and TGF beta, linking malignant cells and tumor-infiltrating myeloid cells, a nexus portending a clinically-relevant anticancer treatment.
C1 [Ohnuki, Hidetaka; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Tosato, G (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM tosatog@mail.nih.gov
RI Ohnuki, Hidetaka/E-1877-2012
OI Ohnuki, Hidetaka/0000-0001-8951-3264
NR 10
TC 1
Z9 1
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2162-4011
EI 2162-402X
J9 ONCOIMMUNOLOGY
JI OncoImmunology
PD MAY
PY 2014
VL 3
IS 5
AR e29029
DI 10.4161/onci.29029
PG 2
WC Oncology; Immunology
SC Oncology; Immunology
GA AM6EP
UT WOS:000339956200020
ER
PT J
AU Flegel, WA
Roseff, SD
Tholpady, A
AF Flegel, Willy A.
Roseff, Susan D.
Tholpady, Ashok
TI Phasing-In RHD Genotyping
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Editorial Material
ID WEAK-D; PHENOTYPES; ALLELES; POPULATION; VARIANTS; ANTIGENS; DONORS
C1 [Flegel, Willy A.; Tholpady, Ashok] NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Roseff, Susan D.] Virginia Commonwealth Univ Hlth Syst, Dept Pathol, Richmond, VA USA.
RP Flegel, WA (reprint author), NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM bill.flegel@nih.gov
OI Tholpady, Ashok/0000-0003-3978-9574
FU Intramural NIH HHS [Z99 CL999999]
NR 22
TC 2
Z9 2
U1 0
U2 0
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD MAY
PY 2014
VL 138
IS 5
BP 585
EP 588
DI 10.5858/2013-0509-ED
PG 4
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA AM0TX
UT WOS:000339560900005
PM 24786114
ER
PT J
AU Wakaba, K
Katayama, Y
Sasai, H
Nagao, Y
Kozawa, T
Tanaka, K
AF Wakaba, Kyohsuke
Katayama, Yasutomi
Sasai, Hiroyuki
Nagao, Yoko
Kozawa, Takako
Tanaka, Kiyoji
TI Common Preferences For Weight Loss Programs In Japanese Adults: An
Internet-based Survey
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Wakaba, Kyohsuke; Katayama, Yasutomi; Nagao, Yoko] Kogakkan Univ, Ise, Japan.
[Sasai, Hiroyuki] NIA, NIH, Bethesda, MD 20892 USA.
[Kozawa, Takako; Tanaka, Kiyoji] Univ Tsukuba, Tsukuba, Ibaraki, Japan.
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 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 1436
BP 383
EP 383
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115902279
ER
PT J
AU Christensen, EJ
Chan, L
Keyser, RE
AF Christensen, Eric J.
Chan, Leighton
Keyser, Randall E.
TI Six-Minute Walk Distance and Fatigability in Patients with Interstitial
Lung Disease
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Christensen, Eric J.; Chan, Leighton] NIH, Bethesda, MD 20892 USA.
[Keyser, Randall E.] George Mason Univ, Fairfax, VA 22030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 1974
BP 541
EP 541
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115903333
ER
PT J
AU Woolstenhulme, JG
Chan, L
Keyser, RE
AF Woolstenhulme, Joshua G.
Chan, Leighton
Keyser, Randall E.
TI Adaptations To Aerobic Exercise In Interstitial Lung Disease
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Woolstenhulme, Joshua G.; Chan, Leighton] NIH, Bethesda, MD 20892 USA.
[Keyser, Randall E.] George Mason Univ, Fairfax, VA 22030 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 1979
BP 543
EP 543
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115903338
ER
PT J
AU Chin, LMK
Chan, L
Keyser, RE
AF Chin, Lisa M. K.
Chan, Leighton
Keyser, Randall E.
TI Cardiorespiratory Function and Aerobic Exercise Training in Patients
with Traumatic Brain Injury
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Chin, Lisa M. K.; Keyser, Randall E.] George Mason Univ, Fairfax, VA 22030 USA.
[Chan, Leighton] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 2014
BP 554
EP 554
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115903373
ER
PT J
AU Schrager, MA
Schrack, JA
Simonsick, EM
Ferrucci, L
AF Schrager, Matthew A.
Schrack, Jennifer A.
Simonsick, Eleanor M.
Ferrucci, Luigi
TI The Association between Energy Availability and Physical Activity in
Older Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Schrager, Matthew A.] Stetson Univ, Deland, FL USA.
[Schrack, Jennifer A.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Baltimore, MD 21224 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 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 2420
BP 652
EP 652
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115904225
ER
PT J
AU Kim, M
Kim, H
Sasai, H
Kojima, N
Varadhan, R
AF Kim, Miji
Kim, Hunkyung
Sasai, Hiroyuki
Kojima, Narumi
Varadhan, Ravi
TI Association Between Objectively Measured Sleep Quality and Physical
Function in the Oldest Old
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Kim, Miji; Kim, Hunkyung; Kojima, Narumi] Tokyo Metropolitan Inst Gerontol, Tokyo, Japan.
[Sasai, Hiroyuki] NIA, NIH, Bethesda, MD 20892 USA.
[Varadhan, Ravi] Johns Hopkins Univ, Baltimore, MD 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 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 2671
BP 716
EP 716
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115905008
ER
PT J
AU Keadle, SK
Shiroma, EJ
Freedson, PS
Lee, IM
AF Keadle, Sarah Kozey
Shiroma, Eric J.
Freedson, Patty S.
Lee, I-Min
TI Impact Of Accelerometer Data Processing Decisions On Data From Large
Cohort Studies
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Keadle, Sarah Kozey] NCI, Bethesda, MD 20892 USA.
[Shiroma, Eric J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Freedson, Patty S.] Univ Massachusetts, Amherst, MA 01003 USA.
[Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 2679
BP 718
EP 718
PG 1
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115905015
ER
PT J
AU Arem, H
Moore, SC
Patel, AV
Visvanathan, K
Freedman, M
Linet, MS
Lee, IM
Matthews, CE
AF Arem, Hannah
Moore, Steven C.
Patel, Alpa V.
Visvanathan, Kala
Freedman, Michal
Linet, Martha S.
Lee, I-min
Matthews, Charles E.
TI Leisure Time Physical Activity And Mortality: Is More Better?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
CT 61st Annual Meeting of the American-College-of-Sports-Medicine
CY APR 01-04, 2014
CL Atlanta, GA
SP Amer Coll Sports Med
C1 [Arem, Hannah; Moore, Steven C.; Freedman, Michal; Linet, Martha S.; Matthews, Charles E.] NCI, Bethesda, MD 20892 USA.
[Patel, Alpa V.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Visvanathan, Kala] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA.
[Lee, I-min] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2014
VL 46
IS 5
SU 1
MA 2866
BP 775
EP 776
PG 2
WC Sport Sciences
SC Sport Sciences
GA AL4PW
UT WOS:000339115905197
ER
PT J
AU Liu, LH
Gritz, D
Parent, CA
AF Liu, Lunhua
Gritz, Derek
Parent, Carole A.
TI PKC beta II acts downstream of chemoattractant receptors and mTORC2 to
regulate cAMP production and myosin II activity in neutrophils
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID PROTEIN-KINASE-C; CYCLASE TYPE-II; ADENYLYL-CYCLASE; CELL-MIGRATION;
MYELOID-LEUKEMIA; MAMMALIAN TARGET; SIGNAL RELAY; TURN MOTIF;
PHOSPHORYLATION; CHEMOTAXIS
AB Chemotaxis is a process by which cells polarize and move up a chemical gradient through the spatiotemporal regulation of actin assembly and actomyosin contractility, which ultimately control front protrusions and back retractions. We previously demonstrated that in neutrophils, mammalian target of rapamycin complex 2 (mTORC2) is required for chemoatntractant- mediated activation of adenylyl cyclase 9 (AC9), which converts ATP into cAMP and regulates back contraction through MyoII phosphorylation. Here we study the mechanism by which mTORC2 regulates neutrophil chemotaxis and AC9 activity. We show that inhibition of protein kinase C beta II (PKC beta II) by CPG53353 or short hairpin RNA knockdown severely inhibits chemoattractant-induced cAMP synthesis and chemotaxis in neutrophils. Remarkably, PKC beta II-inhibited cells exhibit specific and severe tail retraction defects. In response to chemoattractant stimulation, phosphorylated PKC beta II, but not PKC alpha, is transiently translocated to the plasma membrane, where it phosphorylates and activates AC9. mTORC2-mediated PKC beta II phosphorylation on its turn motif, but not its hydrophobic motif, is required for membrane translocation of PKC beta II. Inhibition of mTORC2 activity by Rictor knockdown not only dramatically decreases PKC beta II activity, but it also strongly inhibits membrane translocation of PKC beta II. Together our findings show that PKC beta II is specifically required for mTORC2-dependent AC9 activation and back retraction during neutrophil chemotaxis.
C1 [Liu, Lunhua; Gritz, Derek; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX We thank Amy Melpolder and the National Institutes of Health Blood Bank
for providing human blood from healthy volunteers. We also thank the
Parent laboratory members for excellent discussions and suggestions.
This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 64
TC 11
Z9 11
U1 0
U2 2
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAY 1
PY 2014
VL 25
IS 9
BP 1446
EP 1457
DI 10.1091/mbc.E14-01-0037
PG 12
WC Cell Biology
SC Cell Biology
GA AM2AJ
UT WOS:000339650200004
PM 24600048
ER
PT J
AU Ma, XM
Miller, MB
Vishwanatha, KS
Gross, MJ
Wang, YP
Abbott, T
Lam, TT
Mains, RE
Eipper, BA
AF Ma, Xin-Ming
Miller, Megan B.
Vishwanatha, K. S.
Gross, Maegan J.
Wang, Yanping
Abbott, Thomas
Lam, TuKiet T.
Mains, Richard E.
Eipper, Betty A.
TI Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis
through interactions with phosphoinositides and Abl
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID NUCLEOTIDE EXCHANGE-FACTOR; DENDRITIC SPINES; HIPPOCAMPAL-NEURONS;
TYROSINE PHOSPHORYLATION; EXCITATORY SYNAPSES; SYNAPTIC PLASTICITY;
RECEPTOR ACTIVATION; GEF KALIRIN; FACTOR TRIO; PROTEIN
AB Like several Rho GDP/GTP exchange factors (GEFs), Kalirin7 (Kal7) contains an N-terminal Sec14 domain and multiple spectrin repeats. A natural splice variant of Kalrn lacking the Sec14 domain and four spectrin repeats is unable to increase spine formation; our goal was to understand the function of the Sec14 and spectrin repeat domains. Kal7 lacking its Sec14 domain still increased spine formation, but the spines were short. Strikingly, Kal7 truncation mutants containing only the Sec14 domain and several spectrin repeats increased spine formation. The Sec14 domain bound phosphoinositides, a minor but crucial component of cellular membranes, and binding was increased by a phosphomimetic mutation. Expression of KalSec14-GFP in nonneuronal cells impaired receptor-mediated endocytosis, linking Kal7 to membrane trafficking. Consistent with genetic studies placing Abl, a non-receptor tyrosine kinase, and the Drosophila orthologue of Kalrn into the same signaling pathway, Abl1 phosphorylated two sites in the fourth spectrin repeat of Kalirin, increasing its sensitivity to calpain-mediated degradation. Treating cortical neurons of the wild-type mouse, but not the Kal7(KO) mouse, with an Abl inhibitor caused an increase in linear spine density. Phosphorylation of multiple sites in the N-terminal Sec14/spectrin region of Kal7 may allow coordination of the many signaling pathways contributing to spine morphogenesis.
C1 [Ma, Xin-Ming; Miller, Megan B.; Vishwanatha, K. S.; Gross, Maegan J.; Wang, Yanping; Mains, Richard E.; Eipper, Betty A.] Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA.
[Abbott, Thomas; Lam, TuKiet T.] Yale Univ, WM Keck Fdn, Biotechnol Resource Lab, Yale NIDA Neuroprote Ctr, New Haven, CT 06511 USA.
RP Eipper, BA (reprint author), Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT 06030 USA.
EM ma@uchc.edu; eipper@uchc.edu
FU National Institutes of Health [DK-32948, DA-15464, DA-23082, P30
DA018343]; Scoville Endowment; Janice and Rodney Reynolds Endowment
FX This work was supported by grants from the National Institutes of Health
(DK-32948, DA-15464, DA-23082, and P30 DA018343) and by support from the
Scoville Endowment and the Janice and Rodney Reynolds Endowment. We
thank Darlene D'Amato for incomparable technical assistance, Laura
Urbanski for assistance with the calpain studies, Kathrin Wilczak and
Mary LoPresti for assistance with sample preparation, Lisa Chung for
help with pTyr quantitation, and Prashant Mandela for assistance with
the KalSRKO mice.
NR 84
TC 6
Z9 6
U1 1
U2 2
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAY 1
PY 2014
VL 25
IS 9
BP 1458
EP 1471
DI 10.1091/mbc.E13-04-0215
PG 14
WC Cell Biology
SC Cell Biology
GA AM2AJ
UT WOS:000339650200005
PM 24600045
ER
PT J
AU Dittmer, TA
Sahni, N
Kubben, N
Hill, DE
Vidal, M
Burgess, RC
Roukos, V
Misteli, T
AF Dittmer, Travis A.
Sahni, Nidhi
Kubben, Nard
Hill, David E.
Vidal, Marc
Burgess, Rebecca C.
Roukos, Vassilis
Misteli, Tom
TI Systematic identification of pathological lamin A interactors
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID DREIFUSS MUSCULAR-DYSTROPHY; GILFORD-PROGERIA-SYNDROME; PROTEIN-PROTEIN
INTERACTIONS; NUCLEAR LAMIN; AUTOSOMAL-DOMINANT; LMNA GENE; COMPOUND
HETEROZYGOSITY; DILATED CARDIOMYOPATHY; PARTIAL LIPODYSTROPHY; MUTATION
ANALYSIS
AB Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by > 300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype-phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A-binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome-wide ORFeome library, we identified and validated 337 lamin A-binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson-Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)-like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein-protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes.
C1 [Dittmer, Travis A.; Kubben, Nard; Burgess, Rebecca C.; Roukos, Vassilis; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Sahni, Nidhi; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02215 USA.
[Sahni, Nidhi; Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Sahni, Nidhi; Hill, David E.; Vidal, Marc] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
RI Roukos, Vassilis/K-6248-2012
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Progeria Research
Foundation; National Institutes of Health [HG001715, HG006066]
FX We thank Song Yi, Sam Pevzner, Ty Voss, and Orna Cohen-Fix for technical
expertise. Imaging was performed in the National Cancer Institute
High-Throughput Imaging Facility. This work was in part supported by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research, the Progeria
Research Foundation, and National Institutes of Health grants HG001715
and HG006066.
NR 69
TC 11
Z9 11
U1 0
U2 4
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAY 1
PY 2014
VL 25
IS 9
BP 1493
EP 1510
DI 10.1091/mbc.E14-02-0733
PG 18
WC Cell Biology
SC Cell Biology
GA AM2AJ
UT WOS:000339650200008
PM 24623722
ER
PT J
AU Johnson, JPS
Kumar, P
Koulnis, M
Patel, M
Simin, K
AF Johnson, Jacob P. S.
Kumar, Prashant
Koulnis, Miroslav
Patel, Milan
Simin, Karl
TI Crucial and Novel Cancer Drivers in a Mouse Model of Triple-negative
Breast Cancer
SO CANCER GENOMICS & PROTEOMICS
LA English
DT Article
DE Breast cancer; CGH; integrative analysis; tumor suppressor; oncogene;
mouse model; triple-negative; Wnt; Myc; Arid; Mapk; LCE
ID EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; MOLECULAR
CHARACTERIZATION; ARRAY CGH; PATHWAYS; TUMORS; RECEPTOR; INDUCE; DEATH;
IDENTIFICATION
AB Background: We previously developed a mouse model of breast cancer that mimics human triple-negative breast cancer (TNBC) by inactivating the Retinoblastoma (Rb), Transformation related protein 53 (p53), and Breast cancer 1 (Brca1) pathways in the mammary gland. Despite inactivation of all three tumor suppressors throughout the epithelium, low tumor multiplicity indicated that malignant carcinoma progression requires additional oncogenic stimuli. Materials and Methods: In order to identify collaborating genetic events, we performed integrated analysis of 18 tumors (eight tumors with inactivation of pRbf/Brca1/p53 and ten tumors with inactivation of pRbf/p53) using comparative genomic hybridization and global gene expression. We then conducted flow cytometric analysis, immunostaining, tumorsphere, and cell viability assays. Results: Copy number aberrations were correlated with the transcript levels of 7.55% of genes spanned by the altered genomic regions. Recurrent genomic losses spanning large regions of chromosomes 4 and 10 included several cell death genes. Among the amplified genes were well-known drivers of tumorigenesis including Wingless-related MMTV integration site 2 (Wnt2), as well as potentially novel driver mutations including the Late cornified envelope (LCE) gene family. These tumors have a stem/luminal progenitor phenotype and active beta-catenin signaling. Tumorsphere formation and cell survival are suppressed by Wnt pathway inhibitors. Conclusion: Our novel mouse model mimics human TNBC and provides a platform to triage the pathways that underlie malignant tumor progression.
C1 [Johnson, Jacob P. S.; Simin, Karl] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
[Kumar, Prashant] ASTAR, Inst Mol & Cell Biol, Singapore, Singapore.
[Koulnis, Miroslav] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Patel, Milan] Wright Ctr Grad Med Educ, Scranton, PA USA.
RP Simin, K (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA.
EM karl.simin@umassmed.edu
FU ACS [IRG-93-033-15]; Simeon J. Fortin Charitable Foundation; Pink
Revolution Breast Cancer Alliance
FX This work was supported by funding from grant ACS IRG-93-033-15, the
Simeon J. Fortin Charitable Foundation, and the Pink Revolution Breast
Cancer Alliance to KS.
NR 45
TC 3
Z9 3
U1 0
U2 3
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 1109-6535
EI 1790-6245
J9 CANCER GENOM PROTEOM
JI Cancer Genomics Proteomics
PD MAY-JUN
PY 2014
VL 11
IS 3
BP 115
EP 126
PG 12
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA AL8MZ
UT WOS:000339394600001
PM 24969692
ER
PT J
AU Kovalchuk, I
Zhumagulova, Z
Turdiev, T
Reed, BM
AF Kovalchuk, Irina
Zhumagulova, Zhangul
Turdiev, Timur
Reed, Barbara M.
TI GROWTH MEDIUM ALTERATIONS IMPROVE IN VITRO COLD STORAGE OF PEAR
GERMPLASM
SO CRYOLETTERS
LA English
DT Article
DE germplasm storage; in vitro cold storage; mannitol; micropropagation;
nitrogen; Pyrus
ID INVITRO
AB BACKGROUND: Development of new fruit cultivars is dependent on genetic resource collections such as those at the Pomological Garden of the Institute of Horticulture and Viticulture near Almaty, Kazakhstan. The pear germplasm collection of the Pomological Garden contains 615 cultivars and three species. In vitro cold storage of the collection would provide additional security to the field collection. OBJECTIVE: This study was designed to improve medium-term in vitro storage of pear germplasm. METHODS: Shoots of seven pear cultivars (Pyrus communis L.) were stored in plastic five-section bags at 4 degrees C and a 10-h photoperiod (7 mu mol m(-2) s(-1)). Treatments included medium with four carbohydrate sources (3% sucrose, 2% or 3% mannitol, or 2% sucrose + 2% mannitol) with 0.5 mg l(-1) BAP and 0.1 mg l(-1) IBA or without plant growth regulators (PGRs) and at three Murashige and Skoog (MS) nitrogen concentrations (100%, 50% or 25%). RESULTS: Pear shoots remained viable for 9 to 15 months without repropagation on the control MS medium with 3% sucrose without PGRs. There were significant impacts of cultivar and treatment on the duration of cold storage. Shoots of 'Mramornaya' remained viable (rating of >= 2) for 27 months with PGRs and 2% sucrose + 2% mannitol compared to 12 months for the PGR + 3% sucrose treatment. Talgarskaya Krasaviza' stored for 18 months on 2% sucrose + 2% mannitol while all other treatments lasted only 6 to 9 months. Treatments with 0.5 or 1 mg l(-1) abscisic acid (ABA) with 3% sucrose increased storage duration as did reducing the concentration of nitrogen in the medium to 25% without PGRs and with 3% sucrose.
C1 [Kovalchuk, Irina; Zhumagulova, Zhangul; Turdiev, Timur] Inst Plant Biol & Biotechnol, Natl Biotechnol Ctr, Alma Ata 050040, Kazakhstan.
[Reed, Barbara M.] USDA ARS, Natl Clonal Germplasm Repository, Corvallis, OR 97333 USA.
RP Reed, BM (reprint author), USDA ARS, Natl Clonal Germplasm Repository, 33447 Peoria Rd, Corvallis, OR 97333 USA.
EM kovalchuk_i_u@mail.ru; Barbara.Reed@ars.usda.gov
FU International Science and Technology Center [K428]; USDA Agricultural
Research Service CRIS [5358-21000-033D]
FX The project was supported by funds from the International Science and
Technology Center Grant K428 and the USDA Agricultural Research Service
CRIS project 5358-21000-033D.
NR 19
TC 1
Z9 1
U1 0
U2 3
PU CRYO LETTERS
PI LONDON
PA C/O ROYAL VETERINARY COLLEGE, ROYAL COLLEGE ST, LONDON NW1 0TU, ENGLAND
SN 0143-2044
EI 1742-0644
J9 CRYOLETTERS
JI CryoLetters
PD MAY-JUN
PY 2014
VL 35
IS 3
BP 197
EP 203
PG 7
WC Biology; Physiology
SC Life Sciences & Biomedicine - Other Topics; Physiology
GA AL1VA
UT WOS:000338913200005
PM 24997837
ER
PT J
AU Rodriguez, HP
Glenn, BA
Olmos, TT
Krist, AH
Shimada, SL
Kessler, R
Heurtin-Roberts, S
Bastani, R
AF Rodriguez, Hector P.
Glenn, Beth A.
Olmos, Tanya T.
Krist, Alex H.
Shimada, Stephanie L.
Kessler, Rodger
Heurtin-Roberts, Suzanne
Bastani, Roshan
TI Real-World Implementation and Outcomes of Health Behavior and Mental
Health Assessment
SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE
LA English
DT Article
DE Communication; Mental Health; Practice-based Research; Prevention;
Screening
ID PRIMARY-CARE; SCREENING-TEST; VALIDATION; DEPRESSION; RECORDS
AB Background: Assessing patient-reported health behaviors is a critical first step in prioritizing prevention in primary care. We assessed the feasibility of point-of-care behavioral health assessment in 9 diverse primary care practices, including 4 federally qualified health centers (FQHCs), 4 practice-based research network practices, and a Department of Veterans Affairs practice.
Methods: In this prospective mixed-methods study, practices were asked to integrate a standardized paper-based health behavior and mental health assessment into their workflow for >= 50 patients. We used 3 data sources to examine the implementation process: (1) patient responses to the health assessment, (2) patient feedback surveys about how assessments were used during encounters, and (3) post-implementation interviews.
Results: Most nonurgent patients (71%) visiting the participating practices during the implementation period completed the health assessment, but reach varied by practice (range, 59% to 88%). Unhealthy diet, sedentary lifestyle, and stress were the most common patient problems, with similar frequencies observed across practices. The median number of "positive screens" per patient was similar among FQHCs (3.7 positives; standard deviation [SD], 1.8), practice-based research network practices (3.8 positives; SD, 1.9), and the Veterans Affairs clinic (4.1 positives; SD, 2.0). Primary care clinicians discussed assessment results with patients about half of the time (54%), with considerable variation between practices (range, 13% to 66%; lowest use among FQHC clinicians). Although clinicians were interested in routinely implementing assessments, many reported not feeling confident of having resources or support to address all patients' behavioral health needs.
Conclusions: Primary care practices will need to revamp their patient-reported data collection processes to integrate routine health behavior assessments. Implementation support will be required if health assessments are to be actively used as part of routine primary care.
C1 [Rodriguez, Hector P.; Glenn, Beth A.; Olmos, Tanya T.; Bastani, Roshan] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA.
[Glenn, Beth A.; Bastani, Roshan] Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control, Los Angeles, CA 90034 USA.
[Krist, Alex H.] Virginia Commonwealth Univ, Dept Family Med & Populat Hlth, Richmond, VA 23284 USA.
[Shimada, Stephanie L.] VA Healthcare Syst, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Kessler, Rodger] Univ Vermont, Dept Family Med, Burlington, VT 05405 USA.
[Heurtin-Roberts, Suzanne] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA.
RP Rodriguez, HP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Hlth Policy & Management, 50 Univ Hall,Room 245, Berkeley, CA 94720 USA.
EM hrod@berkeley.edu
FU National Institutes of Health/National Cancer Institute [U48DP001946];
National Institutes of Health/National Center for Advancing
Translational Science UCLA Clinical and Translational Science Institute
[UL1TR000124]
FX This research was supported by the National Institutes of
Health/National Cancer Institute (grant no. U48DP001946) and the
National Institutes of Health/National Center for Advancing
Translational Science UCLA Clinical and Translational Science Institute
Grant no. UL1TR000124.
NR 21
TC 6
Z9 7
U1 2
U2 9
PU AMER BOARD FAMILY MEDICINE
PI LEXINGTON
PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA
SN 1557-2625
EI 1558-7118
J9 J AM BOARD FAM MED
JI J. Am. Board Fam. Med.
PD MAY-JUN
PY 2014
VL 27
IS 3
BP 356
EP 366
DI 10.3122/jabfm.2014.03.130264
PG 11
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA AL5IL
UT WOS:000339167000010
PM 24808114
ER
PT J
AU Baek, JH
Rajagopala, SV
Chattoraj, DK
AF Baek, Jong Hwan
Rajagopala, Seesandra V.
Chattoraj, Dhruba K.
TI Chromosome Segregation Proteins of Vibrio cholerae as Transcription
Regulators
SO MBIO
LA English
DT Article
ID BACILLUS-SUBTILIS CHROMOSOME; P1 PLASMID CENTROMERE; REPLICATION
INITIATION; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; ORIGIN REGION;
SPO0J PARB; GENE; SPORULATION; PARTITION
AB Bacterial ParA and ParB proteins are best known for their contribution to plasmid and chromosome segregation, but they may also contribute to other cell functions. In segregation, ParA interacts with ParB, which binds to parS centromere-analogous sites. In transcription, plasmid Par proteins can serve as repressors by specifically binding to their own promoters and, additionally, in the case of ParB, by spreading from a parS site to nearby promoters. Here, we have asked whether chromosomal Par proteins can likewise control transcription. Analysis of genome-wide ParB1 binding in Vibrio cholerae revealed preferential binding to the three known parS1 sites and limited spreading of ParB1 beyond the parS1 sites. Comparison of wild-type transcriptomes with those of Delta parA1, Delta parB1, and Delta parAB1 mutants revealed that two out of 20 genes (VC0067 and VC0069) covered by ParB1 spreading are repressed by both ParB1 and ParA1. A third gene (VC0076) at the outskirts of the spreading area and a few genes further away were also repressed, particularly the gene for an outer membrane protein, ompU (VC0633). Since ParA1 or ParB1 binding was not evident near VC0076 and ompU genes, the repression may require participation of additional factors. Indeed, both ParA1 and ParB1 proteins were found to interact with several V. cholerae proteins in bacterial and yeast two-hybrid screens. These studies demonstrate that chromosomal Par proteins can repress genes unlinked to parS and can do so without direct binding to the cognate promoter DNA.
IMPORTANCE Directed segregation of chromosomes is essential for their maintenance in dividing cells. Many bacteria have genes (par) that were thought to be dedicated to segregation based on analogy to their roles in plasmid maintenance. It is becoming clear that chromosomal par genes are pleiotropic and that they contribute to diverse processes such as DNA replication, cell division, cell growth, and motility. One way to explain the pleiotropy is to suggest that Par proteins serve as or control other transcription factors. We tested this model by determining how Par proteins affect genome-wide transcription activity. We found that genes implicated in drug resistance, stress response, and pathogenesis were repressed by Par. Unexpectedly, the repression did not involve direct Par binding to cognate promoter DNA, indicating that the repression may involve Par interactions with other regulators. This pleiotropy highlights the degree of integration of chromosomal Par proteins into cellular control circuitries.
C1 [Baek, Jong Hwan; Chattoraj, Dhruba K.] NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rajagopala, Seesandra V.] J Craig Venter Inst, Rockville, MD USA.
RP Chattoraj, DK (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM chattoraj@nih.gov
FU Intramural Research Program, Center for Cancer Research; National Cancer
Institute; National Institutes of Health [GM079710]
FX This work was supported by the Intramural Research Program, Center for
Cancer Research, the National Cancer Institute, and National Institutes
of Health grant GM079710 to S.V.R.
NR 40
TC 4
Z9 4
U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAY-JUN
PY 2014
VL 5
IS 3
AR e01061-14
DI 10.1128/mBio.01061-14
PG 8
WC Microbiology
SC Microbiology
GA AL1HH
UT WOS:000338875900004
PM 24803519
ER
PT J
AU Bantysh, O
Serebryakova, M
Makarova, KS
Dubiley, S
Datsenko, KA
Severinov, K
AF Bantysh, Olga
Serebryakova, Marina
Makarova, Kira S.
Dubiley, Svetlana
Datsenko, Kirill A.
Severinov, Konstantin
TI Enzymatic Synthesis of Bioinformatically Predicted Microcin C-Like
Compounds Encoded by Diverse Bacteria
SO MBIO
LA English
DT Article
ID BIOSYNTHETIC GENE-CLUSTER; ESCHERICHIA-COLI; PLASMID GENES; PANTOCIN-A;
DATABASE; AMINOPEPTIDASE; SPECIFICITY; MATURATION; RESISTANCE; PEPTIDASE
AB The Trojan horse Escherichia coli antibiotic microcin C (McC) consists of a heptapeptide attached to adenosine through a phosphoramidate linkage. McC is synthesized by the MccB enzyme, which terminally adenylates the ribosomally synthesized heptapeptide precursor MccA. The peptide part is responsible for McC uptake; it is degraded inside the cell to release a toxic nonhydrolyzable aspartyl-adenylate. Bionformatic analysis reveals that diverse bacterial genomes encoding mccB homologues also contain adjacent short open reading frames that may encode MccA-like adenylation substrates. Using chemically synthesized predicted peptide substrates and recombinant cognate MccB protein homologs, adenylated products were obtained in vitro for predicted MccA peptide-MccB enzyme pairs from Helicobacter pylori, Streptococcus thermophilus, Lactococcus johnsonii, Bartonella washoensis, Yersinia pseudotuberculosis, and Synechococcus sp. Some adenylated products were shown to inhibit the growth of E. coli by targeting aspartyl-tRNA synthetase, the target of McC.
IMPORTANCE Our results prove that McC-like adenylated peptides are widespread and are encoded by both Gram-negative and Gram-positive bacteria and by cyanobacteria, opening ways for analyses of physiological functions of these compounds and for creation of microcin C-like antibiotics targeting various bacteria.
C1 [Bantysh, Olga; Serebryakova, Marina; Dubiley, Svetlana; Severinov, Konstantin] Russian Acad Sci, Inst Gene Biol, Moscow, Russia.
[Bantysh, Olga; Severinov, Konstantin] St Petersburg State Polytech Univ, St Petersburg, Russia.
[Serebryakova, Marina] Moscow MV Lomonosov State Univ, Moscow, Russia.
[Makarova, Kira S.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Datsenko, Kirill A.] Purdue Univ, W Lafayette, IN 47907 USA.
[Severinov, Konstantin] Skolkovo Inst Sci & Technol, Skolkovo, Russia.
RP Severinov, K (reprint author), Russian Acad Sci, Inst Gene Biol, Moscow, Russia.
EM severik@waksman.rutgers.edu
RI Serebryakova, Marina/E-2986-2012; Severinov, Konstantin/C-8545-2016
FU Russian Academy of Sciences; Ministry of Education and Science of the
Russian Federation [14.B25.31.0004]; U.S. Department of Health and Human
Services
FX Work in K.S.'s laboratories is supported by Russian Academy of Sciences
Presidium Nanotechnology and Molecular and Cellular Biology program
grants and by the Ministry of Education and Science of the Russian
Federation project 14.B25.31.0004 grant. The MALDI MS facility became
available to us in the framework of the Moscow State University
Development Program (PNG 5.13). K. M. is supported by intramural funds
of the U.S. Department of Health and Human Services (allocated to the
National Library of Medicine).
NR 34
TC 6
Z9 6
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAY-JUN
PY 2014
VL 5
IS 3
AR e01059-14
DI 10.1128/mBio.01059-14
PG 11
WC Microbiology
SC Microbiology
GA AL1HH
UT WOS:000338875900005
PM 24803518
ER
PT J
AU Chen, L
Mathema, B
Pitout, JDD
DeLeo, FR
Kreiswirth, BN
AF Chen, Liang
Mathema, Barun
Pitout, Johann D. D.
DeLeo, Frank R.
Kreiswirth, Barry N.
TI Epidemic Klebsiella pneumoniae ST258 Is a Hybrid Strain
SO MBIO
LA English
DT Article
ID SEQUENCE TYPE 258; MOLECULAR EPIDEMIOLOGY; HISTORICAL-PERSPECTIVE;
EVOLUTIONARY GENETICS; ST11 CLONE; CARBAPENEMASES; IDENTIFICATION;
ENTEROBACTERIACEAE; SURVEILLANCE; EXPANSION
AB Carbapenem-resistant Enterobacteriaceae (CRE), especially Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae, pose an urgent threat in health facilities in the United States and worldwide. K. pneumoniae isolates classified as sequence type 258 (ST258) by multilocus sequence typing are largely responsible for the global spread of KPC. A recent comparative genome study revealed that ST258 K. pneumoniae strains are two distinct genetic clades; however, the molecular origin of ST258 largely remains unknown, and our understanding of the evolution of the two genetic clades is incomplete. Here we compared the genetic structures and single-nucleotide polymorphism (SNP) distributions in the core genomes of strains from two ST258 clades and other STs (ST11, ST442, and ST42). We identified an similar to 1.1-Mbp region on ST258 genomes that is homogeneous to that of ST442, while the rest of the ST258 genome resembles that of ST11. Our results suggest ST258 is a hybrid clone-80% of the genome originated from ST11-like strains and 20% from ST442-like strains. Meanwhile, we sequenced an ST42 strain that carries the same K-antigen-encoding capsule polysaccharide biosynthesis gene (cps) region as ST258 clade I strains. Comparison of the cps-harboring regions between the ST42 and ST258 strains (clades I and II) suggests the ST258 clade I strains evolved from a clade II strain as a result of cps region replacement. Our findings unravel the molecular evolution history of ST258 strains, an important first step toward the development of diagnostic, therapeutic, and vaccine strategies to combat infections caused by multidrug-resistant K. pneumoniae.
IMPORTANCE Recombination events and replacement of chromosomal regions have been documented in various bacteria, and these events have given rise to successful pathogenic clones. Here we used comparative genomic analyses to discover that the ST258 K. pneumoniae genome is a hybrid-80% of the chromosome is homologous to ST11 strains, while the remaining 20% is homologous to that of ST442. Meanwhile, a recent study indicated that ST258 strains can be segregated into two ST258 clades, with distinct capsule polysaccharide gene (cps) regions. Our analysis suggests ST258 clade I strains evolved from clade II through homologous recombination of cps region. Horizontal transfer of the cps region appears to be a key element driving the molecular diversification in K. pneumoniae strains. These findings not only extend our understanding of the molecular evolution of ST258 but are an important step toward the development of effective control and treatment strategies for multidrug-resistant K. pneumoniae.
C1 [Chen, Liang; Mathema, Barun; Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst Ctr, Newark, NJ 07102 USA.
[Mathema, Barun] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Pitout, Johann D. D.] Calgary Lab Serv, Div Microbiol, Calgary, AB, Canada.
[Pitout, Johann D. D.] Univ Calgary, Dept Pathol, Calgary, AB, Canada.
[Pitout, Johann D. D.] Univ Calgary, Dept Lab Med, Calgary, AB, Canada.
[Pitout, Johann D. D.] Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB, Canada.
[DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Kreiswirth, BN (reprint author), Rutgers State Univ, New Jersey Med Sch, Publ Hlth Res Inst Ctr, Newark, NJ 07102 USA.
EM kreiswba@njms.rutgers.edu
OI DeLeo, Frank/0000-0003-3150-2516
FU National Institutes of Health [1R01AI090155]; Intramural Research
Program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX This work was supported in part by a grant (to B.N.K.) from the National
Institutes of Health (1R01AI090155) and the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 36
TC 34
Z9 34
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAY-JUN
PY 2014
VL 5
IS 3
AR e01355-14
DI 10.1128/mBio.01355-14
PG 8
WC Microbiology
SC Microbiology
GA AL1HH
UT WOS:000338875900012
PM 24961694
ER
PT J
AU Hryckowian, AJ
Battesti, A
Lemke, JJ
Meyer, ZC
Welch, RA
AF Hryckowian, Andrew J.
Battesti, Aurelia
Lemke, Justin J.
Meyer, Zachary C.
Welch, Rodney A.
TI IraL Is an RssB Anti-adaptor That Stabilizes RpoS during Logarithmic
Phase Growth in Escherichia coli and Shigella
SO MBIO
LA English
DT Article
ID GENERAL STRESS-RESPONSE; GRAM-NEGATIVE BACTERIA; STRAINS; SYSTEM;
VIRULENCE; PROTEIN; TRANSCRIPTION; EXPRESSION; NETWORK; ROLES
AB RpoS (sigma(S)), the general stress response sigma factor, directs the expression of genes under a variety of stressful conditions. Control of the cellular sigma(S) concentration is critical for appropriately scaled sigma(S)-dependent gene expression. One way to maintain appropriate levels of sigma(S) is to regulate its stability. Indeed, sigma(S) degradation is catalyzed by the ClpXP protease and the recognition of sigma(S) by ClpXP depends on the adaptor protein RssB. Three anti-adaptors (IraD, IraM, and IraP) exist in Escherichia coli K-12; each interacts with RssB and inhibits RssB activity under different stress conditions, thereby stabilizing sigma(S). Unlike K-12, some E. coli isolates, including uropathogenic E. coli strain CFT073, show comparable cellular levels of sigma(S) during the logarithmic and stationary growth phases, suggesting that there are differences in the regulation of sigma(S) levels among E. coli strains. Here, we describe IraL, an RssB anti-adaptor that stabilizes sigma(S) during logarithmic phase growth in CFT073 and other E. coli and Shigella strains. By immunoblot analyses, we show that IraL affects the levels and stability of sigma(S) during logarithmic phase growth. By computational and PCR-based analyses, we reveal that iraL is found in many E. coli pathotypes but not in laboratory-adapted strains. Finally, by bacterial two-hybrid and copurification analyses, we demonstrate that IraL interacts with RssB by a mechanism distinct from that used by other characterized anti-adaptors. We introduce a fourth RssB anti-adaptor found in E. coli species and suggest that differences in the regulation of sigma(S) levels may contribute to host and niche specificity in pathogenic and nonpathogenic E. coli strains.
IMPORTANCE Bacteria must cope with a variety of environmental conditions in order to survive. RpoS (sigma(S)), the general stress response sigma factor, directs the expression of many genes under stressful conditions in both pathogenic and nonpathogenic Escherichia coli strains. The regulation of sigma(S) levels and activity allows appropriately scaled sigma(S)-dependent gene expression. Here, we describe IraL, an RssB anti-adaptor that, unlike previously described anti-adaptors, stabilizes sigma(S) during the logarithmic growth phase in the absence of additional stress. We also demonstrate that iraL is found in a large number of E. coli and Shigella isolates. These data suggest that strains containing iraL are able to initiate sigma(S)-dependent gene expression under conditions under which strains without iraL cannot. Therefore, IraL-mediated sigma(S) stabilization may contribute to host and niche specificity in E. coli.
C1 [Hryckowian, Andrew J.; Lemke, Justin J.; Meyer, Zachary C.; Welch, Rodney A.] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
[Battesti, Aurelia] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Welch, RA (reprint author), Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
EM rawelch@wisc.edu
FU National Institutes of Health (NIH) [R01-DK063250-07]; NIH, National
Cancer Institute, Center for Cancer Research
FX This work was supported by National Institutes of Health (NIH) grant
R01-DK063250-07, and A.B. was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 32
TC 3
Z9 3
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAY-JUN
PY 2014
VL 5
IS 3
AR e01043-14
DI 10.1128/mBio.01043-14
PG 8
WC Microbiology
SC Microbiology
GA AL1HH
UT WOS:000338875900031
PM 24865554
ER
PT J
AU Ladner, JT
Beitzel, B
Chain, PSG
Davenport, MG
Donaldson, EF
Frieman, M
Kugelman, JR
Kuhn, JH
O'Rear, J
Sabeti, PC
Wentworth, DE
Wiley, MR
Yu, GY
Sozhamannan, S
Bradburne, C
Palacios, G
AF Ladner, Jason T.
Beitzel, Brett
Chain, Patrick S. G.
Davenport, Matthew G.
Donaldson, Eric F.
Frieman, Matthew
Kugelman, Jeffrey R.
Kuhn, Jens H.
O'Rear, Jules
Sabeti, Pardis C.
Wentworth, David E.
Wiley, Michael R.
Yu, Guo-Yun
Sozhamannan, Shanmuga
Bradburne, Christopher
Palacios, Gustavo
CA Threat Characterization Consortium
TI Standards for Sequencing Viral Genomes in the Era of High-Throughput
Sequencing
SO MBIO
LA English
DT Editorial Material
ID DISCOVERY; VIRUSES; CORONAVIRUS; POPULATION; DIVERSITY; CHINA
AB Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five "standard" categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques.
C1 [Ladner, Jason T.; Beitzel, Brett; Kugelman, Jeffrey R.; Wiley, Michael R.; Yu, Guo-Yun; Palacios, Gustavo] US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD 21702 USA.
[Chain, Patrick S. G.] Los Alamos Natl Lab, Bioinformat & Analyt Team, Biosci Div, Los Alamos, NM USA.
[Davenport, Matthew G.; Bradburne, Christopher] Johns Hopkins Univ, Appl Phys Lab, Natl Secur Syst Biol Ctr, Asymmetr Operat Sect, Laurel, MD USA.
[Donaldson, Eric F.; O'Rear, Jules] US FDA, Silver Spring, MD USA.
[Frieman, Matthew] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA.
[Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
[Sabeti, Pardis C.] Broad Inst, Cambridge, MA USA.
[Wentworth, David E.] J Craig Venter Inst, Rockville, MD USA.
[Threat Characterization Consortium] Def Threat Reduct Agcy, Threat Characterizat Consortium, Ft Belvoir, VA USA.
[Sozhamannan, Shanmuga] GoldBelt Raven LLC, Frederick, MD USA.
[Sozhamannan, Shanmuga] Joint Program Execut Off, Crit Reagents Program, Ft Detrick, MD USA.
RP Ladner, JT (reprint author), US Army, Med Res Inst Infect Dis, Ctr Genome Sci, Ft Detrick, MD 21702 USA.
EM jason.t.ladner.ctr@mail.mil; gustavo.f.palacios.ctr@mail.mil
RI Kuhn, Jens H./B-7615-2011; Palacios, Gustavo/I-7773-2015;
OI Kuhn, Jens H./0000-0002-7800-6045; Palacios,
Gustavo/0000-0001-5062-1938; Wentworth, David/0000-0002-5190-980X;
Chain, Patrick/0000-0003-3949-3634
FU NIAID NIH HHS [HHSN272200700016I]; PHS HHS [HHSN272200700016I]
NR 23
TC 20
Z9 20
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD MAY-JUN
PY 2014
VL 5
IS 3
AR e01360-14
DI 10.1128/mBio.01360-14
PG 5
WC Microbiology
SC Microbiology
GA AL1HH
UT WOS:000338875900037
PM 24939889
ER
PT J
AU Thompson, SJ
Millecamps, M
Aliaga, A
Seminowicz, DA
Low, LA
Bedell, BJ
Stone, LS
Schweinhardt, P
Bushnell, MC
AF Thompson, Scott J.
Millecamps, Magali
Aliaga, Antonio
Seminowicz, David A.
Low, Lucie A.
Bedell, Barry J.
Stone, Laura S.
Schweinhardt, Petra
Bushnell, M. Catherine
TI Metabolic brain activity suggestive of persistent pain in a rat model of
neuropathic pain
SO NEUROIMAGE
LA English
DT Article
DE MicroPET; FDG; Neuropathic pain; Spared nerve injury; Formalin model
ID NERVE INJURY; PERIPHERAL MONONEUROPATHY; SOMATOSENSORY CORTEX;
SCIATIC-NERVE; FORMALIN TEST; ONGOING PAIN; STIMULATION; ALLODYNIA;
DISORDERS; FMRI
AB Persistent pain is a central characteristic of neuropathic pain conditions in humans. Knowing whether rodent models of neuropathic pain produce persistent pain is therefore crucial to their translational applicability. We investigated the spared nerve injury (SNI) model of neuropathic pain and the formalin pain model in rats using positron emission tomography (PET) with the metabolic tracer [18F]fluorodeoxyglucose (FDG) to determine if there is ongoing brain activity suggestive of persistent pain. For the formalin model, under brief anesthesia we injected one hindpaw with 5% formalin and the FDG tracer into a tail vein. We then allowed the animals to awaken and observed pain behavior for 30 min during the FDG uptake period. The rat was then anesthetized and placed in the scanner for static image acquisition, which took place between minutes 45 and 75 post-tracer injection. A single reference rat brain magnetic resonance image (MRI) was used to align the PET images with the Paxinos and Watson rat brain atlas. Increased glucose metabolism was observed in the somatosensory region associated with the injection site (S1 hindlimb contralateral), Si jaw/upper lip and cingulate cortex. Decreases were observed in the prelimbic cortex and hippocampus. Second, SNI rats were scanned 3 weeks post-surgery using the same scanning paradigm, and region-of-interest analyses revealed increased metabolic activity in the contralateral 51 hindlimb. Finally, a second cohort of SNI rats was scanned while anesthetized during the tracer uptake period, and the Si hindlimb increase was not observed. Increased brain activity in the somatosensory cortex of SNI rats resembled the activity produced with the injection of formalin, suggesting that the SNI model may produce persistent pain. The lack of increased activity in Si hindlimb with general anesthetic demonstrates that this effect can be blocked, as well as highlights the importance of investigating brain activity in awake and behaving rodents. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Thompson, Scott J.; Millecamps, Magali; Stone, Laura S.; Schweinhardt, Petra] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ H3G 0G1, Canada.
[Low, Lucie A.; Bushnell, M. Catherine] NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Aliaga, Antonio; Bedell, Barry J.] McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Small Anim Imaging Lab, Montreal, PQ H3A 2B4, Canada.
[Millecamps, Magali; Stone, Laura S.; Schweinhardt, Petra] McGill Univ, Fac Dent, Montreal, PQ H3A 2T5, Canada.
[Seminowicz, David A.] Univ Maryland, Sch Dent, Dept Neural & Pain Sci, Baltimore, MD 21201 USA.
[Bedell, Barry J.; Stone, Laura S.; Schweinhardt, Petra] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
[Thompson, Scott J.] McGill Univ, Integrated Program Neurosci, Montreal, PQ H3A 2T5, Canada.
RP Thompson, SJ (reprint author), 3640 Univ St, Montreal, PQ H3A 2B3, Canada.
EM scott.thompson4@mail.mcgill.ca
RI Seminowicz, David/F-8732-2015;
OI Seminowicz, David/0000-0003-3111-3756; Low, Lucie/0000-0001-6082-8625
FU AstraZeneca; Pfizer Canada; Intramural Research Program of the National
Center for Complementary and Alternative Medicine, National Institutes
of Health; Louise and Alan Edwards Foundation
FX This work was partially funded by grants to Dr. Bushnell from
AstraZeneca & Pfizer Canada. This research was also partially funded by
the Intramural Research Program of the National Center for Complementary
and Alternative Medicine, National Institutes of Health. Scott J
Thompson is supported by The Louise and Alan Edwards Foundation's
Edwards PhD. Studentship in Pain Research.
NR 51
TC 5
Z9 5
U1 0
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 MAY 1
PY 2014
VL 91
BP 344
EP 352
DI 10.1016/j.neuroimage.2014.01.020
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AL1VJ
UT WOS:000338914100035
PM 24462776
ER
PT J
AU Miller, RK
Darrah, TH
Friedman, A
Li, A
Stodgell, CJ
Landrigan, P
Walker, C
Clark, EB
Dole, N
Thiex, N
Swanson, J
Culhane, J
Szabo, S
Moye, J
AF Miller, R. K.
Darrah, T. H.
Friedman, A.
Li, A.
Stodgell, C. J.
Landrigan, P.
Walker, C.
Clark, E. B.
Dole, N.
Thiex, N.
Swanson, J.
Culhane, J.
Szabo, S.
Moye, J.
TI Enviromnental exposures during pregnancy: US National Children's Study
formative research investigation
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the Neurobehavioral-Teratology-Society
CY JUN 28-JUL 02, 2014
CL Bellevue, WA
SP Neurobehavioral Teratol Soc
C1 [Miller, R. K.; Darrah, T. H.; Friedman, A.; Li, A.; Stodgell, C. J.; Landrigan, P.; Walker, C.; Clark, E. B.; Dole, N.; Thiex, N.; Swanson, J.; Culhane, J.; Szabo, S.; Moye, J.] Natl Childrens Study Placental Consortium, Bethesda, MD USA.
[Miller, R. K.; Friedman, A.; Stodgell, C. J.] Univ Rochester, Rochester, NY USA.
[Darrah, T. H.] Ohio State Univ, Columbus, OH 43210 USA.
[Li, A.] Univ Illinois, Chicago, IL USA.
[Landrigan, P.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Szabo, S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Walker, C.] Univ Calif Davis, Davis, CA 95616 USA.
Univ Calif Irvine, Irvine, CA USA.
[Clark, E. B.] Univ Utah, Salt Lake City, UT USA.
[Thiex, N.] S Dakota State Univ, Brookings, SD 57007 USA.
[Dole, N.] Univ N Carolina, Chapel Hill, NC USA.
[Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Moye, J.] NIH, Bethesda, MD 20892 USA.
RI Li, An/A-3395-2008
OI Li, An/0000-0002-8476-8783
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
EI 1872-9738
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2014
VL 43
MA NBTS 10
BP 79
EP 79
DI 10.1016/j.ntt.2014.04.013
PG 1
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA AK7QC
UT WOS:000338621800020
ER
PT J
AU Moghe, GD
Hufnagel, DE
Tang, HB
Xiao, YL
Dworkin, I
Town, CD
Conner, JK
Shiu, SH
AF Moghe, Gaurav D.
Hufnagel, David E.
Tang, Haibao
Xiao, Yongli
Dworkin, Ian
Town, Christopher D.
Conner, Jeffrey K.
Shiu, Shin-Han
TI Consequences of Whole-Genome Triplication as Revealed by Comparative
Genomic Analyses of the Wild Radish Raphanus raphanistrum and Three
Other Brassicaceae Species
SO PLANT CELL
LA English
DT Article
ID DUPLICATED GENES; ARABIDOPSIS-THALIANA; FLOWERING PLANTS; PREFERENTIAL
RETENTION; POLYPLOID FORMATION; PROVIDES INSIGHT; EVOLUTION; SEQUENCE;
RAPA; MODEL
AB Polyploidization events are frequent among flowering plants, and the duplicate genes produced via such events contribute significantly to plant evolution. We sequenced the genome of wild radish (Raphanus raphanistrum), a Brassicaceae species that experienced a whole-genome triplication event prior to diverging from Brassica rapa. Despite substantial gene gains in these two species compared with Arabidopsis thaliana and Arabidopsis lyrata, similar to 70% of the orthologous groups experienced gene losses in R. raphanistrum and B. rapa, with most of the losses occurring prior to their divergence. The retained duplicates show substantial divergence in sequence and expression. Based on comparison of A. thaliana and R. raphanistrum ortholog floral expression levels, retained radish duplicates diverged primarily via maintenance of ancestral expression level in one copy and reduction of expression level in others. In addition, retained duplicates differed significantly from genes that reverted to singleton state in function, sequence composition, expression patterns, network connectivity, and rates of evolution. Using these properties, we established a statistical learning model for predicting whether a duplicate would be retained postpolyploidization. Overall, our study provides new insights into the processes of plant duplicate loss, retention, and functional divergence and highlights the need for further understanding factors controlling duplicate gene fate.
C1 [Moghe, Gaurav D.; Shiu, Shin-Han] Michigan State Univ, Genet Program, E Lansing, MI 48824 USA.
[Moghe, Gaurav D.; Shiu, Shin-Han] Michigan State Univ, Program Quantitat Biol, E Lansing, MI 48824 USA.
[Hufnagel, David E.; Conner, Jeffrey K.; Shiu, Shin-Han] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA.
[Tang, Haibao; Town, Christopher D.] J Craig Venter Inst, Rockville, MD 20850 USA.
[Xiao, Yongli] NIAID, NIH, Bethesda, MD 20892 USA.
[Dworkin, Ian] Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA.
[Conner, Jeffrey K.] Michigan State Univ, Kellogg Biol Stn, E Lansing, MI 48824 USA.
RP Shiu, SH (reprint author), Michigan State Univ, Genet Program, E Lansing, MI 48824 USA.
EM shius@msu.edu
OI Moghe, Gaurav/0000-0002-8761-064X; Conner, Jeffrey/0000-0003-1613-5826;
Shiu, Shin-Han/0000-0001-6470-235X
FU National Science Foundation [DBI-0638591, DEB-0919452, IOS-1126998]
FX We thank Cindy Mills and Melissa Lehti-Shiu for maintaining the radish
plants, Melissa for reading the article, Barry Williams for discussion,
Alicia Massa for helping isolate genomic DNA samples, Robin Buell for
discussion on sequencing strategies, John Johnston for computational
support, Guangxi Wu for assistance with orthology prediction, Alex
Seddon for assistance with SVM analyses, and James Birchler and the
reviewers for providing valuable comments allowing further improvement
of the article. This work was partially supported by National Science
Foundation Grants DBI-0638591 to J.K.C., C.D.T., S.-H.S., and Y.X.,
DEB-0919452 to J.K.C., ID., and S.H.S., and IOS-1126998 to S.H.S. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the article. This is KBS
contribution #1776.
NR 74
TC 26
Z9 27
U1 3
U2 42
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 1040-4651
EI 1532-298X
J9 PLANT CELL
JI Plant Cell
PD MAY
PY 2014
VL 26
IS 5
BP 1925
EP 1937
DI 10.1105/tpc.114.124297
PG 13
WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
GA AK9UA
UT WOS:000338771700014
PM 24876251
ER
PT J
AU Van Laethem, F
Saba, I
Tikhonova, AN
Singer, A
AF Van Laethem, Francois
Saba, Ingrid
Tikhonova, Anastasia N.
Singer, Alfred
TI Crucial role of the CD4 and CD8 co-receptors in antigen recognition of
lymphocytes T alpha beta
SO M S-MEDECINE SCIENCES
LA French
DT News Item
ID THYMIC SELECTION; AMINO-ACIDS; MHC; REPERTOIRE
C1 [Van Laethem, Francois; Saba, Ingrid; Tikhonova, Anastasia N.; Singer, Alfred] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
RP Van Laethem, F (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM vanlaetf@mail.nih.gov
RI Tikhonova, Anastasia/F-1186-2015
NR 7
TC 0
Z9 0
U1 0
U2 0
PU EDP SCIENCES S A
PI LES ULIS CEDEX A
PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A,
FRANCE
SN 0767-0974
J9 M S-MED SCI
JI M S-Med. Sci.
PD MAY
PY 2014
VL 30
IS 5
BP 511
EP 513
DI 10.1051/medsci/20143005012
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AK5FM
UT WOS:000338450100012
PM 24939536
ER
PT J
AU Negrouk, A
Lacombe, D
Trimble, EL
Seymour, M
AF Negrouk, Anastassia
Lacombe, Denis
Trimble, Edward L.
Seymour, Matthew
TI Clinical research for rare cancers: is it a reality in the global
regulatory landscape? The international rare cancer initiative
SO EXPERT OPINION ON ORPHAN DRUGS
LA English
DT Review
DE clinical trials; international rare cancer initiative; rare cancers;
regulatory
ID EORTC
AB Introduction: Rare cancers together account for about 22% of new cancer diagnoses each year, which is more than any single common cancer. They constitute a serious public health problem with distinctive challenges. Compared with common cancers, less is known about their etiology and molecular pathology, and therapeutic options are mostly poorly evidence based with outcomes that are on average inferior to those of more common cancers. There is, therefore, a pressing need for well-organized clinical research to address these deficiencies. The International rare cancer initiative (IRCI) was formed in 2011 with the aim of stimulating and facilitating the development of international clinical trials for patients with rare cancers, and so helping to establish better, more evidence-based treatments. As of October 2013, 8 clinical trials are in design, in set up or recruiting, in seven rare cancer types, giving IRCI a good understanding of the current research conditions for rare cancer.
Areas covered: This paper sets the scene of clinical research in rare cancers and presents an overview of organizational, methodological, regulatory and financial challenges facing researchers in this field. It also proposes possible steps to improve the research environment for the future.
Expert opinion: Based on our observations, we believe that measures should be taken to improve the integration of research across international boundaries, to improve the funding of academic research and to better integrate the research capacity of industry with the public sector for the greater benefits of patients and society.
C1 [Negrouk, Anastassia] European Org Res Treatment Canc, Int Regulatory & Intergroup Off, B-1200 Brussels, Belgium.
[Lacombe, Denis] European Org Res & Treatment Canc Headquarters, B-1200 Brussels, Belgium.
[Trimble, Edward L.] NCI, Ctr Global Hlth, Washington, DC USA.
[Seymour, Matthew] Natl Inst Hlth, Res Canc Res Network, Leeds, W Yorkshire, England.
RP Negrouk, A (reprint author), European Org Res Treatment Canc, Int Regulatory & Intergroup Off, Ave E Mounier 83-11, B-1200 Brussels, Belgium.
EM anastassia.negrouk@eortc.be
NR 8
TC 1
Z9 1
U1 1
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 2167-8707
J9 EXPERT OPIN ORPHAN D
JI Exp. Opin. Orphan Drugs
PD MAY
PY 2014
VL 2
IS 5
BP 433
EP 440
DI 10.1517/21678707.2014.888948
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AK2WC
UT WOS:000338279400001
ER
PT J
AU Kliger, AS
Chertow, GM
Levin, NW
Beck, GJ
Daugirdas, JT
Eggers, PW
Larive, B
Rocco, MV
Greene, T
AF Kliger, Alan S.
Chertow, Glenn M.
Levin, Nathan W.
Beck, Gerald J.
Daugirdas, John T.
Eggers, Paul W.
Larive, Brett
Rocco, Michael V.
Greene, Tom
TI LONG-TERM EFFECTS OF FREQUENT IN-CENTER HEMODIALYSIS: FHN DAILY TRIAL
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Meeting Abstract
CT 51st Congress of the
European-Renal-Association(ERA)/European-Dialysis-and-Transplant-Associa
tion (EDTA)
CY MAY 31-JUN 03, 2014
CL Amsterdam, NETHERLANDS
SP European Renal Assoc, European Dialysis & Transplant Assoc
C1 [Kliger, Alan S.] Yale Univ, Sch Med, New Haven, CT USA.
[Chertow, Glenn M.] Stanford Univ, Stanford, CA 94305 USA.
[Levin, Nathan W.] Renal Res Inst, New York, NY USA.
[Beck, Gerald J.; Larive, Brett] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Daugirdas, John T.] Univ Illinois, Chicago, IL USA.
[Eggers, Paul W.] NIDDK, Bethesda, MD 20892 USA.
[Rocco, Michael V.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Greene, Tom] Univ Utah, Salt Lake City, UT USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAY
PY 2014
VL 29
SU 3
MA MO037
BP 37
EP 38
PG 2
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA AJ9FQ
UT WOS:000338013500089
ER
PT J
AU Rocco, M
Daugirdas, J
Greene, T
Lockridge, R
Chan, C
Pierratos, A
Lindsay, R
Larive, B
Chertow, G
Beck, G
Eggers, P
Kliger, A
Grp, FT
AF Rocco, Michael
Daugirdas, John
Greene, Tom
Lockridge, Robert
Chan, Christopher
Pierratos, Andreas
Lindsay, Robert
Larive, Brett
Chertow, Glenn
Beck, Gerald
Eggers, Paul
Kliger, Alan
Grp, F. H. N. Trial
TI MORTALITY DURING EXTENDED FOLLOW-UP IN THE FREQUENT HEMODIALYSIS NETWORK
NOCTURNAL TRIAL
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Meeting Abstract
CT 51st Congress of the
European-Renal-Association(ERA)/European-Dialysis-and-Transplant-Associa
tion (EDTA)
CY MAY 31-JUN 03, 2014
CL Amsterdam, NETHERLANDS
SP European Renal Assoc, European Dialysis & Transplant Assoc
C1 [Rocco, Michael] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Daugirdas, John] Univ Illinois, Chicago, IL USA.
[Greene, Tom] Univ Utah, Salt Lake City, UT USA.
[Lockridge, Robert] Univ Virginia, Lynchburg, VA USA.
[Chan, Christopher; Pierratos, Andreas] Univ Toronto, Toronto, ON, Canada.
[Lindsay, Robert] London Hlth Sci, London, ON, Canada.
[Larive, Brett] Cleveland Clin, Cleveland, OH 44106 USA.
[Chertow, Glenn] Stanford Univ, Stanford, CA 94305 USA.
[Eggers, Paul] NIDDK, NIH, Bethesda, MD 20892 USA.
[Kliger, Alan] Yale New Haven Med Ctr, New Haven, CT 06504 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 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAY
PY 2014
VL 29
SU 3
MA MO035
BP 37
EP 37
PG 1
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA AJ9FQ
UT WOS:000338013500087
ER
PT J
AU Koroshetz, WJ
Landis, S
AF Koroshetz, Walter J.
Landis, Story
TI Neurology's Stake in Foundational Neuroscience Research
SO ANNALS OF NEUROLOGY
LA English
DT Editorial Material
C1 [Koroshetz, Walter J.; Landis, Story] NINDS, NIH, Bethesda, MD 20892 USA.
RP Koroshetz, WJ (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD MAY
PY 2014
VL 75
IS 5
BP 621
EP 622
DI 10.1002/ana.24161
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AJ5EV
UT WOS:000337706100002
PM 24756692
ER
PT J
AU Wohlfarth, A
Pang, SK
Zhu, MS
Gandhi, AS
Scheidweiler, KB
Huestis, MA
AF Wohlfarth, Ariane
Pang, Shaokun
Zhu, Mingshe
Gandhi, Adarsh S.
Scheidweiler, Karl B.
Huestis, Marilyn A.
TI Metabolism of RCS-8, a synthetic cannabinoid with cyclohexyl structure,
in human hepatocytes by high-resolution MS
SO BIOANALYSIS
LA English
DT Article
ID CHROMATOGRAPHY-MASS SPECTROMETRY; URINARY METABOLITES; QUANTITATIVE
MEASUREMENT; LIQUID-CHROMATOGRAPHY; IDENTIFICATION; JWH-018; 1ST;
MIXTURES; AM-2201; UR-144
AB Background: Since 2008, synthetic cannabinoids are major new designer drugs of abuse. They are extensively metabolized and excreted in urine, but limited human metabolism data are available. As there are no reports on the metabolism of RCS-8, a scheduled phenylacetylindole synthetic cannabinoid with an N-cyclohexylethyl moiety, we investigated metabolism of this new designer drug by human hepatocytes and high resolution MS. Methods: After human hepatocyte incubation with RCS-8, samples were analyzed on a TripleTOF 5600+ mass spectrometer with time-of-flight survey scan and information-dependent acquisition triggered product ion scans. Data mining of the accurate mass full scan and product ion spectra employed different data processing algorithms. Results & Conclusion: More than 20 RCS-8 metabolites were identified, products of oxidation, demethylation, and glucuronidation. Major metabolites and targets for analytical methods were hydroxyphenyl RCS-8 glucuronide, a variety of hydroxycyclohexyl-hydroxyphenyl RCS-8 glucuronides, hydroxyphenyl RCS-8, as well as the demethyl-hydroxycyclohexyl RCS-8 glucuronide.
C1 [Wohlfarth, Ariane; Gandhi, Adarsh S.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Pang, Shaokun] AB SCIEX, Redwood City, CA 94065 USA.
[Zhu, Mingshe] Bristol Myers Squibb Res Dev, Dept Biotransformat, Princeton, NJ 08543 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU AB SCIEX; Intramural Research Program, National Institute on Drug Abuse,
National Institutes of Health
FX This research was funded by AB SCIEX and the Intramural Research
Program, National Institute on Drug Abuse, National Institutes of
Health. A Wohlfarth, A Gandhi, K Scheidweiler and M Huestis are
employees at the National Institute on Drug Abuse, National Institutes
of Health. S Pang is employed by AB SCIEX, M Zhu is employed by
Bristol-Myers Squibb. The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 26
TC 11
Z9 11
U1 2
U2 13
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1757-6180
EI 1757-6199
J9 BIOANALYSIS
JI Bioanalysis
PD MAY
PY 2014
VL 6
IS 9
BP 1187
EP 1200
DI 10.4155/bio.14.1
PG 14
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AJ8HX
UT WOS:000337945200013
PM 24946920
ER
PT J
AU Yamaguchi, Y
Hearing, VJ
AF Yamaguchi, Yuji
Hearing, Vincent J.
TI Melanocytes and Their Diseases
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID DYSCHROMATOSIS SYMMETRICA HEREDITARIA; MESENCHYMAL-EPITHELIAL
INTERACTIONS; KOYANAGI-HARADA SYNDROME; STEM-CELLS; GENERALIZED
VITILIGO; EPIDERMAL MELANOCYTES; SUSCEPTIBILITY LOCI; SKIN PIGMENTATION;
GENE-EXPRESSION; HAIR-FOLLICLES
AB Human melanocytes are distributed not only in the epidermis and in hair follicles but also in mucosa, cochlea (ear), iris (eye), and mesencephalon (brain) among other tissues. Melanocytes, which are derived from the neural crest, are unique in that they produce eu-/pheomelanin pigments in unique membrane-bound organelles termed melanosomes, which can be divided into four stages depending on their degree of maturation. Pigmentation production is determined by three distinct elements: enzymes involved in melanin synthesis, proteins required for melanosome structure, and proteins required for their trafficking and distribution. Many genes are involved in regulating pigmentation at various levels, and mutations in many of them cause pigmentary disorders, which can be classified into three types: hyperpigmentation (including melasma), hypopigmentation (including oculocutaneous albinism [OCA]), and mixed hyper-/hypopigmentation (including dyschromatosis symmetrica hereditaria). We briefly review vitiligo as a representative of an acquired hypopigmentation disorder.
C1 [Yamaguchi, Yuji] AbbVie GK, Tokyo 1086302, Japan.
[Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
FU Intramural Research Program of the National Cancer Institute at NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute at NIH. Y.Y. is an AbbVie employee and may
receive AbbVie stock, stock options, and grants.
NR 82
TC 11
Z9 11
U1 4
U2 13
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD MAY
PY 2014
VL 4
IS 5
AR a017046
DI 10.1101/cshperspect.a017046
PG 18
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AJ9HV
UT WOS:000338020100005
ER
PT J
AU Reiss, D
Eccles, JS
Nielsen, L
AF Reiss, David
Eccles, Jacquelynne S.
Nielsen, Lisbeth
TI Conscientiousness and Public Health: Synthesizing Current Research to
Promote Healthy Aging
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE conscientiousness; personality; aging; life course; interventions
ID 5-FACTOR MODEL; ENVIRONMENTAL-INFLUENCES; PERSONALITY; CHILDHOOD; TWIN
AB In this special section, 9 studies and 6 commentaries make a unique contribution to the study of personality. They focus on the five-factor model and, in particular, one of those 5: conscientiousness. This trait has had astonishing success in the actuarial prediction of adaptive outcomes in adulthood and aging, but we have little understanding of the mechanisms that account for this actuarial success. The current studies and comments marshal current knowledge of conscientiousness to advance a mechanistic understanding of these predictions and to exploit that understanding toward interventions to enhance robust adult development and healthy aging. In this introductory article, we underscore the strategy we used to invite presentations and commentary. First, we sought a clearer definition of conscientiousness and a review of its assessment. Second, we sought a review of how the components of this complex trait develop in childhood and are assembled across development. Third, we sought an understanding of how mechanisms linking conscientiousness and health might be transformed across the life span. Fourth, we scrutinized naturally occurring factors that moderate the links between conscientiousness and health for clues to successful interventions. Finally, we sought ways to pull these analyses together to outline the framework for a program of interventions that, collectively, might be applicable at specific points across the life span. Six commentaries place this project in sharp relief. They remind us that the causal status of the associations between conscientiousness and health, reported throughout our 9 studies, are uncertain at best. Second, they remind us that the concept of conscientiousness is still too spare: It fails to embody the social skills required for conscientious behavior, the moral judgment of self or other implicit in its assessment, or the neurobiological mechanisms that might account for differences among individuals. Third, they raise a potent counterfactual: What, in a practical sense, does conceptualization or assessment of conscientiousness contribute-if anything-to the design of interventions to enhance conscientious behavior?
C1 [Reiss, David] Yale Univ, Yale Child Study Ctr, New Haven, CT 06519 USA.
[Eccles, Jacquelynne S.] Univ Michigan, Inst Social Res, Ann Arbor, MI 48109 USA.
[Nielsen, Lisbeth] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA.
RP Reiss, D (reprint author), Yale Univ, Yale Child Study Ctr, 230 South Frontage Rd, New Haven, CT 06519 USA.
EM david.reiss@yale.edu
NR 38
TC 6
Z9 7
U1 1
U2 17
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
EI 1939-0599
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAY
PY 2014
VL 50
IS 5
BP 1303
EP 1314
DI 10.1037/a0036473
PG 12
WC Psychology, Developmental
SC Psychology
GA AJ7TR
UT WOS:000337901000001
PM 24773105
ER
PT J
AU Su, LJ
Fontham, ETH
AF Su, L. Joseph
Fontham, Elizabeth T. H.
TI Prostate cancer: an occupational hazard?
SO FUTURE ONCOLOGY
LA English
DT Editorial Material
DE aggressiveness; diet; lifestyle; occupation; prostate cancer; sitting;
whole-body vibration
ID EPIDEMIOLOGIC EVIDENCE; CONSTRUCTION WORKERS; PHYSICAL-ACTIVITY;
BODY-SIZE; RISK; COHORT
C1 [Su, L. Joseph] NCI, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Fontham, Elizabeth T. H.] Louisiana State Univ Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA.
RP Su, LJ (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E212, Rockville, MD 20850 USA.
EM sulj@mail.nih.gov
NR 20
TC 1
Z9 1
U1 0
U2 1
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1479-6694
EI 1744-8301
J9 FUTURE ONCOL
JI Future Oncol.
PD MAY
PY 2014
VL 10
IS 6
BP 903
EP 906
DI 10.2217/fon.14.33
PG 4
WC Oncology
SC Oncology
GA AJ8FO
UT WOS:000337938300001
PM 24941975
ER
PT J
AU Gotea, V
Elnitski, L
AF Gotea, Valer
Elnitski, Laura
TI Ascertaining regions affected by GC-biased gene conversion through
weak-to-strong mutational hotspots
SO GENOMICS
LA English
DT Article
DE GC-biased gene conversion (gBGC); Positive selection; Weak-to-strong
mutation bias; Mutation hotspots; Modified Tang-Lewontin test
ID RECENT POSITIVE SELECTION; HUMAN GENOME; ACCELERATED EVOLUTION;
NONCODING SEQUENCES; MOLECULAR EVOLUTION; PROTEIN EVOLUTION; HUMANS;
SIGNATURES; FOXP2; ADAPTATION
AB A major objective for evolutionary biology is to identify regions affected by positive selection. High d(N)/d(S) values for proteins and accelerated lineage-specific substitution rates for non-coding regions are considered classic signatures of positive selection. However, these could also be the result of non-adaptive phenomena, such as GC-biased gene conversion (gBGC), which favors the fixation of strong (C/G) over weak (A/T) nucleotides. Recent estimates indicate that gBGC affected up to 20% of regions with signatures of positive selection. Here we evaluate the impact of gBGC through its molecular signature of weak-to-strong mutational hotspots. We implemented specific modifications to the test proposed by Tang and Lewontin (1999) for identifying regions of differential variability and applied it to regions previously investigated for the influence of gBGC While we found significant agreement with previous reports, our results suggest a smaller influence of gBGC than previously estimated, warranting further development of methods for its detection. Published by Elsevier Inc.
C1 [Gotea, Valer; Elnitski, Laura] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Gotea, V (reprint author), 5625 Fishers Ln,Room 5N-01S, Rockville, MD 20852 USA.
EM vgotea@nih.gov
OI Gotea, Valer/0000-0001-7857-3309
FU Intramural Program of the National Human Genome Research Institute,
National Institutes of Health
FX This work was supported by the Intramural Program of the National Human
Genome Research Institute, National Institutes of Health. We thank F.
Sanchez-Vega for critical review of the manuscript and of the
mathematical formulae, and three anonymous reviewers for constructive
suggestions.
NR 44
TC 0
Z9 0
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 0888-7543
EI 1089-8646
J9 GENOMICS
JI Genomics
PD MAY-JUN
PY 2014
VL 103
IS 5-6
BP 349
EP 356
DI 10.1016/j.ygeno.2014.04.001
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA AJ9AY
UT WOS:000338000400005
PM 24727706
ER
PT J
AU Lavender, KJ
Messer, RJ
Race, B
Hasenkrug, KJ
AF Lavender, Kerry J.
Messer, Ronald J.
Race, Brent
Hasenkrug, Kim J.
TI Production of bone marrow, liver, thymus (BLT) humanized mice on the
C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-) background
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE ELT humanized mice; C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-);
Hematopoiesis
ID RECEPTOR-GAMMA-CHAIN; HEMATOPOIETIC STEM-CELLS; IMMUNODEFICIENT MICE;
RECONSTITUTION; ENGRAFTMENT; RAG2
AB C57BL/6 Rag2(-/-)gamma(-/-)(c)CD47(-/-) triple-knockout mice engrafted with fetal human bone marrow, liver, thymus (TKO-BLT) not only develop high levels of multi-lineage hematopoiesis but also organized lymphoid tissues including mesenteric lymph nodes, splenic follicles and gut-associated lymphoid tissues of human origin. A unique advantage of these mice is that they sustain human cell and tissue engraftment long-term without the development of graft versus host disease. Thus they can be used for long-term studies not previously feasible with other models. The production of TKO-BLT mice to obtain healthy mice with high level reconstitution of human cells and tissues requires specialized methods that are presented in detail. Published by Elsevier B.V.
C1 [Lavender, Kerry J.; Messer, Ronald J.; Race, Brent; Hasenkrug, Kim J.] NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Hasenkrug, KJ (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM khasenkrug@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, NIH, USA
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, NIH, USA.
NR 14
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
EI 1872-7905
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD MAY
PY 2014
VL 407
BP 127
EP 134
DI 10.1016/j.jim.2014.04.008
PG 8
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA AJ7GZ
UT WOS:000337866500016
PM 24769067
ER
PT J
AU Berkman, BE
Hull, SC
Eckstein, L
AF Berkman, Benjamin E.
Hull, Sara Chandros
Eckstein, Lisa
TI The unintended implications of blurring the line between research and
clinical care in a genomic age
SO PERSONALIZED MEDICINE
LA English
DT Article
DE ancillary care; incidental findings; legal liability; research ethics;
secondary findings; whole-genome sequencing
ID MANAGING INCIDENTAL FINDINGS; GENETIC RESEARCH; SECONDARY VARIANTS;
WORKING GROUP; RECOMMENDATIONS; MEDICINE; FUTURE; RETURN; EXOME;
PERSPECTIVES
AB While the development of next-generation sequencing technology has had a paradigm-changing impact on biomedical research, there is likely to be a gap between discovery of therapeutic benefits in research and actual adoption of the new technology into clinical practice. This gap can create pressure on the research enterprise to provide individualized care more typical of the clinic setting because it is uniquely accessible in research. This blurring of the line between research and clinical care is understandable, and perhaps even inevitable. But even if the gap is only transitory, such a blurring can have lasting implications, both by expanding obligations imposed on researchers, but also by challenging long-held ethical views. We explore this idea, focusing on how the dissolving distinction between research and clinical care has influenced the vigorous debate around how researchers should manage genetic findings (sometimes separated into primary and incidental or secondary findings) resulting from research.
C1 [Berkman, Benjamin E.; Hull, Sara Chandros] NHGRI, Off Clin Director, Bethesda, MD 20892 USA.
[Berkman, Benjamin E.; Hull, Sara Chandros; Eckstein, Lisa] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Eckstein, Lisa] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia.
RP Berkman, BE (reprint author), NHGRI, Off Clin Director, Bethesda, MD 20892 USA.
EM berkmanbe@mail.nih.gov
RI Eckstein, Lisa/J-7747-2014
OI Eckstein, Lisa/0000-0002-7161-7521
FU Intramural Research Program of the National Human Genome Research
Institute; Department of Bioethics at the NIH Clinical Center
FX The preparation of this manuscript was funded by the Intramural Research
Program of the National Human Genome Research Institute and the
Department of Bioethics at the NIH Clinical Center. The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 55
TC 6
Z9 6
U1 1
U2 12
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
EI 1744-828X
J9 PERS MED
JI Pers. Med.
PD MAY
PY 2014
VL 11
IS 3
BP 285
EP 295
DI 10.2217/pme.14.3
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AJ7ZZ
UT WOS:000337922800011
PM 25506378
ER
PT J
AU Avnir, Y
Tallarico, AS
Zhu, Q
Bennett, AS
Connelly, G
Sheehan, J
Sui, JH
Fahmy, A
Huang, CY
Cadwell, G
Bankston, LA
McGuire, AT
Stamatatos, L
Wagner, G
Liddington, RC
Marasco, WA
AF Avnir, Yuval
Tallarico, Aimee S.
Zhu, Quan
Bennett, Andrew S.
Connelly, Gene
Sheehan, Jared
Sui, Jianhua
Fahmy, Amr
Huang, Chiung-yu
Cadwell, Greg
Bankston, Laurie A.
McGuire, Andrew T.
Stamatatos, Leonidas
Wagner, Gerhard
Liddington, Robert C.
Marasco, Wayne A.
TI Molecular Signatures of Hemagglutinin Stem-Directed Heterosubtypic Human
Neutralizing Antibodies against Influenza A Viruses
SO PLOS PATHOGENS
LA English
DT Article
ID MEMORY B-CELLS; SOMATIC HYPERMUTATION; STALK ANTIBODIES; GERMINAL
CENTER; MARGINAL ZONE; COPY-NUMBER; IMMUNOGLOBULIN; REPERTOIRE; DESIGN;
DOMAIN
AB Recent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs). Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met) and Phe54), and CDR-H3-Tyr at positions 98 +/- 1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-eta recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/pol eta restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a) facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination.
C1 [Avnir, Yuval; Tallarico, Aimee S.; Zhu, Quan; Bennett, Andrew S.; Connelly, Gene; Sheehan, Jared; Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Med, Boston, MA 02115 USA.
[Fahmy, Amr; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Huang, Chiung-yu] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Cadwell, Greg; Bankston, Laurie A.; Liddington, Robert C.] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA USA.
[McGuire, Andrew T.; Stamatatos, Leonidas] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
RP Avnir, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Med, 44 Binney St, Boston, MA 02115 USA.
EM wayne_marasco@dfci.harvard.edu
FU National Institutes of Health [NIAID U01-AI074518, NIAID P01
AI094419-01]; Defense Advanced Research Projects Agency
[W911NF-10-1-0266]
FX This work was supported by the following grants from the National
Institutes of Health: NIAID U01-AI074518 to WAM and RCL and NIAID P01
AI094419-01 to LS. This work was also funded by the Defense Advanced
Research Projects Agency's "7-Day Biodefense" program under contract #
W911NF-10-1-0266 to WAM. The views expressed are those of the author and
do not reflect the official policy or position of the Department of
Defense or the U.S. Government. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 55
TC 29
Z9 29
U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004103
DI 10.1371/journal.ppat.1004103
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300021
PM 24788925
ER
PT J
AU Aydin, I
Weber, S
Snijder, B
Ventayol, PS
Kuhbacher, A
Becker, M
Day, PM
Schiller, JT
Kann, M
Pelkmans, L
Helenius, A
Schelhaas, M
AF Aydin, Inci
Weber, Susanne
Snijder, Berend
Ventayol, Pilar Samperio
Kuehbacher, Andreas
Becker, Miriam
Day, Patricia M.
Schiller, John T.
Kann, Michael
Pelkmans, Lucas
Helenius, Ari
Schelhaas, Mario
TI Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown
for Nuclear Import of Human Papillomaviruses
SO PLOS PATHOGENS
LA English
DT Article
ID MINOR CAPSID PROTEIN; VIRUS-LIKE PARTICLES; SMALL-MOLECULE INHIBITOR;
HEPARAN-SULFATE; MONOCLONAL-ANTIBODIES; HUMAN KERATINOCYTES; ALPHA(6)
INTEGRIN; CELLULAR ENTRY; VIRAL-DNA; INFECTION
AB A two-step, high-throughput RNAi silencing screen was used to identify host cell factors required during human papillomavirus type 16 (HPV16) infection. Analysis of validated hits implicated a cluster of mitotic genes and revealed a previously undetermined mechanism for import of the viral DNA (vDNA) into the nucleus. In interphase cells, viruses were endocytosed, routed to the perinuclear area, and uncoated, but the vDNA failed to be imported into the nucleus. Upon nuclear envelope perforation in interphase cells HPV16 infection occured. During mitosis, the vDNA and L2 associated with host cell chromatin on the metaphase plate. Hence, we propose that HPV16 requires nuclear envelope breakdown during mitosis for access of the vDNA to the nucleoplasm. The results accentuate the value of genes found by RNAi screens for investigation of viral infections. The list of cell functions required during HPV16 infection will, moreover, provide a resource for future virus-host cell interaction studies.
C1 [Aydin, Inci; Weber, Susanne; Ventayol, Pilar Samperio; Becker, Miriam; Schelhaas, Mario] Univ Munster, ZMBE, Inst Mol Virol & Med Biochem, Emmy Noether Grp Virus Endocytosis, D-48149 Munster, Germany.
[Aydin, Inci; Weber, Susanne; Ventayol, Pilar Samperio; Becker, Miriam; Schelhaas, Mario] Cluster Excellence EXC1003, Munster, Germany.
[Snijder, Berend; Pelkmans, Lucas] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland.
[Kuehbacher, Andreas; Helenius, Ari] ETH, Inst Biochem, Zurich, Switzerland.
[Day, Patricia M.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Kann, Michael] Univ Bordeaux Segalen, Lab Microbiol Fondamentale & Pathogenicite, Bordeaux, France.
RP Aydin, I (reprint author), Univ Munster, ZMBE, Inst Mol Virol & Med Biochem, Emmy Noether Grp Virus Endocytosis, D-48149 Munster, Germany.
EM schelhaas@uni-muenster.de
RI Kim, Seongman/N-6910-2014;
OI Snijder, Berend/0000-0003-3386-6583
FU German Research Foundation (DFG) [SCHE 1552/2-1, GRK 1409/C2, EXC 1003];
ETH Zurich; Swiss National Science Foundation (SNF); European Research
Council (ERC); University of Zurich; European Union; SystemsX.ch; Swiss
Initiative in Systems Biology
FX MS was supported by the German Research Foundation (DFG, grants SCHE
1552/2-1, GRK 1409/C2, EXC 1003 (partly)). AH was supported by the ETH
Zurich, and by grants from the Swiss National Science Foundation (SNF)
and the European Research Council (ERC). LP was supported by the ETH
Zurich, the University of Zurich, the European Union, and by
SystemsX.ch, the Swiss Initiative in Systems Biology. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 85
TC 35
Z9 35
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004162
DI 10.1371/journal.ppat.1004162
PG 19
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300058
PM 24874089
ER
PT J
AU Dumas, A
Amiable, N
Vaccari, JPD
Chae, JJ
Keane, RW
Lacroix, S
Vallieres, L
AF Dumas, Aline
Amiable, Nathalie
Vaccari, Juan Pablo de Rivero
Chae, Jae Jin
Keane, Robert W.
Lacroix, Steve
Vallieres, Luc
TI The Inflammasome Pyrin Contributes to Pertussis Toxin-Induced IL-1 beta
Synthesis, Neutrophil Intravascular Crawling and Autoimmune
Encephalomyelitis
SO PLOS PATHOGENS
LA English
DT Article
ID FAMILIAL MEDITERRANEAN FEVER; CENTRAL-NERVOUS-SYSTEM; MYELIN
OLIGODENDROCYTE GLYCOPROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS;
MULTIPLE-SCLEROSIS PATIENTS; REGULATORY T-CELLS;
INFECTIOUS-MONONUCLEOSIS; IL-6-DEFICIENT MICE; BRAIN VASCULATURE; COMMON
MUTATIONS
AB Microbial agents can aggravate inflammatory diseases, such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). An example is pertussis toxin (PTX), a bacterial virulence factor commonly used as an adjuvant to promote EAE, but whose mechanism of action is unclear. We have reported that PTX triggers an IL-6-mediated signaling cascade that increases the number of leukocytes that patrol the vasculature by crawling on its luminal surface. In the present study, we examined this response in mice lacking either TLR4 or inflammasome components and using enzymatically active and inactive forms of PTX. Our results indicate that PTX, through its ADP-ribosyltransferase activity, induces two series of events upstream of IL-6: 1) the activation of TLR4 signaling in myeloid cells, leading to pro-IL-1 beta synthesis; and 2) the formation of a pyrin-dependent inflammasome that cleaves pro-IL-1 beta into its active form. In turn, IL-1 beta stimulates nearby stromal cells to secrete IL-6, which is known to induce vascular changes required for leukocyte adhesion. Without pyrin, PTX does not induce neutrophil adhesion to cerebral capillaries and is less effective at inducing EAE in transgenic mice with encephalitogenic T lymphocytes. This study identifies the first microbial molecule that activates pyrin, a mechanism by which infections may influence MS and a potential therapeutic target for immune disorders.
C1 [Dumas, Aline; Amiable, Nathalie; Lacroix, Steve; Vallieres, Luc] Univ Hosp Ctr Quebec, Quebec City, PQ, Canada.
[Vaccari, Juan Pablo de Rivero] Univ Miami, Dept Neurol Surg, Miami Project Cure Paralysis, Miami, FL USA.
[Chae, Jae Jin] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Keane, Robert W.] Univ Miami, Dept Physiol & Biophys, Miami, FL USA.
[Lacroix, Steve; Vallieres, Luc] Univ Laval, Dept Mol Med, Quebec City, PQ, Canada.
RP Dumas, A (reprint author), Univ Hosp Ctr Quebec, Quebec City, PQ, Canada.
EM Luc.Vallieres@crchul.ulaval.ca
OI de Rivero Vaccari, Juan Pablo/0000-0002-5460-8834
FU Multiple Sclerosis Society of Canada; Natural Sciences and Engineering
Research Council of Canada; Fonds de Recherche du Quebec en Sante
(FRQS); FRQS
FX This work was supported by grants from the Multiple Sclerosis Society of
Canada and the Natural Sciences and Engineering Research Council of
Canada. LV and SL received Chercheur-Boursier Senior awards from the
Fonds de Recherche du Quebec en Sante (FRQS). NA received a postdoctoral
fellowship from the FRQS. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 95
TC 20
Z9 20
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004150
DI 10.1371/journal.ppat.1004150
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300050
PM 24875775
ER
PT J
AU Jang, MK
Shen, K
McBride, AA
AF Jang, Moon Kyoo
Shen, Kui
McBride, Alison A.
TI Papillomavirus Genomes Associate with BRD4 to Replicate at Fragile Sites
in the Host Genome
SO PLOS PATHOGENS
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; DNA-DAMAGE RESPONSE; E2 PROTEIN; MITOTIC
CHROMOSOMES; S-PHASE; TRANSCRIPTION FACTORS; NUCLEOTIDE-SEQUENCE;
PREFERENTIAL SITES; VIRAL INTEGRATION; SUPER-ENHANCERS
AB It has long been recognized that oncogenic viruses often integrate close to common fragile sites. The papillomavirus E2 protein, in complex with BRD4, tethers the viral genome to host chromatin to ensure persistent replication. Here, we map these targets to a number of large regions of the human genome and name them Persistent E2 and BRD4-Broad Localized Enrichments of Chromatin or PEB-BLOCs. PEB-BLOCs frequently contain deletions, have increased rates of asynchronous DNA replication, and are associated with many known common fragile sites. Cell specific fragile sites were mapped in human C-33 cervical cells by FANCD2 ChIP-chip, confirming the association with PEB-BLOCs. HPV-infected cells amplify viral DNA in nuclear replication foci and we show that these form adjacent to PEB-BLOCs. We propose that HPV replication, which hijacks host DNA damage responses, occurs adjacent to highly susceptible fragile sites, greatly increasing the chances of integration here, as is found in HPV-associated cancers.
C1 [Jang, Moon Kyoo; McBride, Alison A.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Shen, Kui] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
RP Jang, MK (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM amcbride@nih.gov
RI Shen, Kui/E-2764-2015;
OI McBride, Alison/0000-0001-5607-5157
FU Intramural Research Program of NIAID, NIH [ZIA AI000713 LVD]
FX This work was funded by the Intramural Research Program of NIAID, NIH
grant number ZIA AI000713 LVD. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 81
TC 19
Z9 19
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004117
DI 10.1371/journal.ppat.1004117
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300033
PM 24832099
ER
PT J
AU Li, QS
Zhang, YY
Chiu, S
Hu, ZY
Lan, KH
Cha, H
Sodroski, C
Zhang, F
Hsu, CS
Thomas, E
Liang, TJ
AF Li, Qisheng
Zhang, Yong-Yuan
Chiu, Stephan
Hu, Zongyi
Lan, Keng-Hsin
Cha, Helen
Sodroski, Catherine
Zhang, Fang
Hsu, Ching-Sheng
Thomas, Emmanuel
Liang, T. Jake
TI Integrative Functional Genomics of Hepatitis C Virus Infection
Identifies Host Dependencies in Complete Viral Replication Cycle
SO PLOS PATHOGENS
LA English
DT Article
ID NONSTRUCTURAL PROTEIN 5A; CLATHRIN-MEDIATED ENDOCYTOSIS; CELLULAR
COFACTORS; ANTIVIRAL PROTEIN; HUMAN HEPATOCYTES; APOLIPOPROTEIN-E; ENTRY
FACTOR; ALPHA-HELIX; PARTICLES; REQUIRES
AB Recent functional genomics studies including genome-wide small interfering RNA (siRNA) screens demonstrated that hepatitis C virus (HCV) exploits an extensive network of host factors for productive infection and propagation. How these co-opted host functions interact with various steps of HCV replication cycle and exert pro- or antiviral effects on HCV infection remains largely undefined. Here we present an unbiased and systematic strategy to functionally interrogate HCV host dependencies uncovered from our previous infectious HCV (HCVcc) siRNA screen. Applying functional genomics approaches and various in vitro HCV model systems, including HCV pseudoparticles (HCVpp), single-cycle infectious particles (HCVsc), subgenomic replicons, and HCV cell culture systems (HCVcc), we identified and characterized novel host factors or pathways required for each individual step of the HCV replication cycle. Particularly, we uncovered multiple HCV entry factors, including E-cadherin, choline kinase alpha, NADPH oxidase CYBA, Rho GTPase RAC1 and SMAD family member 6. We also demonstrated that guanine nucleotide binding protein GNB2L1, E2 ubiquitin-conjugating enzyme UBE2J1, and 39 other host factors are required for HCV RNA replication, while the deubiquitinating enzyme USP11 and multiple other cellular genes are specifically involved in HCV IRES-mediated translation. Families of antiviral factors that target HCV replication or translation were also identified. In addition, various virologic assays validated that 66 host factors are involved in HCV assembly or secretion. These genes included insulin-degrading enzyme (IDE), a proviral factor, and N-Myc down regulated Gene 1 (NDRG1), an antiviral factor. Bioinformatics meta-analyses of our results integrated with literature mining of previously published HCV host factors allows the construction of an extensive roadmap of cellular networks and pathways involved in the complete HCV replication cycle. This comprehensive study of HCV host dependencies yields novel insights into viral infection, pathogenesis and potential therapeutic targets.
C1 [Li, Qisheng; Zhang, Yong-Yuan; Chiu, Stephan; Hu, Zongyi; Lan, Keng-Hsin; Cha, Helen; Sodroski, Catherine; Zhang, Fang; Hsu, Ching-Sheng; Thomas, Emmanuel; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Li, QS (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM jakel@bdg10.niddk.nih.gov
RI Li, Qisheng/K-1909-2013
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; NIH [N01-DK-7-0004/HHSN26700700004C]
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. Primary human hepatocytes were provided
by the NIH funded Liver Tissue Procurement and Cell Distribution System
(N01-DK-7-0004/HHSN26700700004C, PI-S. Strom, University of Pittsburgh).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 70
TC 33
Z9 34
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004163
DI 10.1371/journal.ppat.1004163
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300059
PM 24852294
ER
PT J
AU Mattera, R
Farias, GG
Mardones, GA
Bonifacino, JS
AF Mattera, Rafael
Farias, Ginny G.
Mardones, Gonzalo A.
Bonifacino, Juan S.
TI Co-assembly of Viral Envelope Glycoproteins Regulates Their Polarized
Sorting in Neurons
SO PLOS PATHOGENS
LA English
DT Article
ID VIRUS FUSION PROTEIN; EMERGENT DEADLY PARAMYXOVIRUS; NIPAH-VIRUS;
EPITHELIAL-CELLS; HIPPOCAMPAL-NEURONS; NERVOUS-SYSTEM; N-GLYCANS;
MEMBRANE-PROTEINS; TARGETING SIGNAL; HENDRA VIRUS
AB Newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. Although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. We studied the polarized sorting of the attachment (NiV-G) and fusion (NiV-F) glycoproteins of Nipah virus (NiV), a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. When expressed individually, NiV-G exhibited a non-polarized distribution, whereas NiV-F was specifically sorted to the somatodendritic domain. Polarized sorting of NiV-F was dependent on interaction of tyrosine-based signals in its cytosolic tail with the clathrin adaptor complex AP-1. Co-expression of NiV-G with NiV-F abolished somatodendritic sorting of NiV-F due to incorporation of NiV-G.NiV-F complexes into axonal transport carriers. We propose that faster biosynthetic transport of unassembled NiV-F allows for its proteolytic activation in the somatodendritic domain prior to association with NiV-G and axonal delivery of NiV-G.NiV-F complexes. Our study reveals how interactions of viral glycoproteins with the host's transport machinery and between themselves regulate their polarized sorting in neurons.
C1 [Mattera, Rafael; Farias, Ginny G.; Mardones, Gonzalo A.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Mattera, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU NICHD, NIH
FX This work was funded by the Intramural Program of NICHD, NIH. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 58
TC 8
Z9 8
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004107
DI 10.1371/journal.ppat.1004107
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300024
PM 24831812
ER
PT J
AU Park, YD
Shin, S
Panepinto, J
Ramos, J
Qiu, J
Frases, S
Albuquerque, P
Cordero, RJB
Zhang, NN
Himmelreich, U
Beenhouwer, D
Bennett, JE
Casadevall, A
Williamson, PR
AF Park, Yoon-Dong
Shin, Soowan
Panepinto, John
Ramos, Jeanie
Qiu, Jin
Frases, Susana
Albuquerque, Patricia
Cordero, Radames J. B.
Zhang, Nannan
Himmelreich, Uwe
Beenhouwer, David
Bennett, John E.
Casadevall, Arturo
Williamson, Peter R.
TI A Role for LHC1 in Higher Order Structure and Complement Binding of the
Cryptococcus neoformans Capsule
SO PLOS PATHOGENS
LA English
DT Article
ID POLYSACCHARIDE CAPSULE; MONOCLONAL-ANTIBODIES; FUSARIUM-OXYSPORUM;
VIRULENCE FACTOR; LACCASE; CELL; ACTIVATION; COMPONENTS; INFECTION;
STRAINS
AB Polysaccharide capsules are important virulence factors for many microbial pathogens including the opportunistic fungus Cryptococcus neoformans. In the present study, we demonstrate an unusual role for a secreted lactonohydrolase of C. neoformans, LHC1 in capsular higher order structure. Analysis of extracted capsular polysaccharide from wild-type and lhc1 (Delta) over bar strains by dynamic and static light scattering suggested a role for the LHC1 locus in altering the capsular polysaccharide, both reducing dimensions and altering its branching, density and solvation. These changes in the capsular structure resulted in LHC1-dependent alterations of antibody binding patterns, reductions in human and mouse complement binding and phagocytosis by the macrophage-like cell line J774, as well as increased virulence in mice. These findings identify a unique molecular mechanism for tertiary structural changes in a microbial capsule, facilitating immune evasion and virulence of a fungal pathogen.
C1 [Park, Yoon-Dong; Qiu, Jin; Zhang, Nannan; Bennett, John E.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Shin, Soowan; Ramos, Jeanie; Williamson, Peter R.] Univ Illinois, Dept Med, Coll Med, Infect Dis Sect, Chicago, IL USA.
[Panepinto, John] SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14260 USA.
[Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Casadevall, Arturo] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Frases, Susana; Albuquerque, Patricia; Cordero, Radames J. B.; Casadevall, Arturo] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10467 USA.
[Frases, Susana] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Lab Ultraestrutura Cellular Hertha Meyer, BR-21941 Rio De Janeiro, Brazil.
[Himmelreich, Uwe] Katholieke Univ Leuven, Div Radiol, Dept Med Diagnost Sci, Biomed NMR Unit, Leuven, Belgium.
[Beenhouwer, David] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA.
[Beenhouwer, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
RP Park, YD (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov
RI Albuquerque, Patricia/H-1403-2011;
OI Cordero, Radames JB/0000-0002-3026-7094
FU United States Public Health Service [NIH-AI45995, AI49371, AI007506,
AI033142, AI47087, HL059842-3, A1033774, A1052733, AI033142.]; Flemish
government [FWO G.0804.11]; KUL [PF10/017]; CAPES-Brazil; NIH, NIAID
FX This work was supported, in part, by United States Public Health Service
Grants NIH-AI45995, AI49371, AI007506, AI033142, AI47087, HL059842-3,
A1033774, A1052733, and AI033142. Flemish governmental funding FWO
G.0804.11 and KUL funding PF10/017 and a CAPES-Brazil/Fulbright
scholarship (PA). This research was also supported, in part, by the
Intramural Research Program of the NIH, NIAID. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 60
TC 5
Z9 5
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD MAY
PY 2014
VL 10
IS 5
AR e1004037
DI 10.1371/journal.ppat.1004037
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AJ5NX
UT WOS:000337732300003
PM 24789368
ER
PT J
AU Anderson, SR
Esposito, D
Gillette, W
Zhu, JY
Baxa, U
McNeil, SE
AF Anderson, Sarah R.
Esposito, Dominic
Gillette, William
Zhu, J. Y.
Baxa, Ulrich
McNeil, Scott E.
TI Enzymatic preparation of nanocrystalline and microcrystalline cellulose
SO TAPPI JOURNAL
LA English
DT Article
ID MICROFIBRILLATED CELLULOSE; FILMS; SUSPENSIONS; HYDROLYSIS; NANOFIBERS;
BEHAVIOR; FIBERS; PULP
AB Traditional cellulose nanocrystal (CNC) production methods use harsh chemicals, are energetically expensive, and result in a hydrophilic sulfate surface chemistry with limited utility. Enzymatic production of CNCs is a less expensive alternative production method that eliminates the need for harsh chemicals and requires much less energy for mechanical fibrillation and heating. Furthermore, enzymes that selectively degrade the amorphous regions of cellulose fibers, and do not significantly digest the crystalline areas, result in CNCs that retain a hydroxyl group surface chemistry. Retention of hydroxyl groups allows for easier chemical manipulation, and thus an expanded commercial potential. Here we show that cellulase from Aspergillus niger is capable of producing CNC and micro-fibrillated cellulose (MFC) from well-solubilized kraft pulp feedstock with minimal processing, and that a chimeric cellulase partially digests kraft pulp and live wood feedstock. Additionally, we show that as a feedstock source, milled pulp from bug-killed dead and downed trees has significantly reduced energy requirements to process the feedstock into elementary fibers and MFCs when compared to live wood feedstock sources.
C1 [Anderson, Sarah R.; Baxa, Ulrich] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Elect Microscopy Lab, Frederick, MD 21702 USA.
[Esposito, Dominic; Gillette, William] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Prot Express Lab, Frederick, MD USA.
[McNeil, Scott E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Nanotechnol Characterizat Lab, Canc Res Technol Program, Frederick, MD USA.
RP Anderson, SR (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Elect Microscopy Lab, Frederick, MD 21702 USA.
EM ncl@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX The authors are grateful to all from Leidos Biomedical Research Inc.;
Vanessa Wall, Jane Jones, Shelley Perkins, and Troy Taylor for cloning
and protein production assistance; Andrew Stephen for help with assay
development; and Rachael M. Crist for assistance with the preparation of
the manuscript. 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 U.
S. Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the U.
S. government or TAPPI.
NR 26
TC 7
Z9 7
U1 4
U2 32
PU TECH ASSOC PULP PAPER IND INC
PI NORCROSS
PA 15 TECHNOLOGY PARK SOUTH, NORCROSS, GA 30092 USA
SN 0734-1415
J9 TAPPI J
JI TAPPI J.
PD MAY
PY 2014
VL 13
IS 5
BP 35
EP 42
PG 8
WC Materials Science, Paper & Wood
SC Materials Science
GA AJ8GI
UT WOS:000337940400005
ER
PT J
AU Anderson, NW
Klein, DM
Dornink, SM
Jespersen, DJ
Kubofcik, J
Nutman, TB
Merrigan, SD
Couturier, MR
Theel, ES
AF Anderson, Neil W.
Klein, Diane M.
Dornink, Sarina M.
Jespersen, Deborah J.
Kubofcik, Joseph
Nutman, Thomas B.
Merrigan, Stephen D.
Couturier, Marc Roger
Theel, Elitza S.
TI Comparison of Three Immunoassays for Detection of Antibodies to
Strongyloides stercoralis
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID HYPERINFECTION SYNDROME; IMPROVED DIAGNOSIS; STOOL SPECIMENS;
RISK-FACTORS; INFECTION; ASSAY
AB Due to the limited sensitivities of stool-based microscopy and/or culture techniques for Strongyloides stercoralis, the detection of antibodies to this intestinal nematode is relied upon as a surrogate for determining exposure status or making a diagnosis of S. stercoralis infection. Here, we evaluated three immunoassays, including the recently released InBios Strongy Detect IgG enzyme-linked immunosorbent assay (ELISA) (InBios International, Inc., Seattle, WA), the SciMedx Strongyloides serology microwell ELISA (SciMedx Corporation, Denville, NJ), and the luciferase immunoprecipitation system (LIPS) assay performed at the National Institutes of Health (NIH), for their detection of IgG antibodies to S. stercoralis. A total of 101 retrospective serum samples, previously submitted for routine S. stercoralis antibody detection using the SciMedx assay, were also evaluated by the InBios and LIPS assays. The qualitative results from each assay were compared using a Venn diagram analysis, to the consensus result among the three assays, and each ELISA was also evaluated using the LIPS assay as the reference standard. By Venn diagram analysis, 65% (66/101) of the samples demonstrated perfect agreement by all three assays. Also, the numbers of samples considered positive or negative by a single method were similar. Compared to the consensus result, the overall percent agreement of the InBios, SciMedx, and LIPS assays were comparable at 87.1%, 84.2%, and 89.1%, respectively. Finally, the two ELISAs performed analogously but demonstrated only moderate agreement (kappa coefficient for the two assays, 0.53) with the LIPS assay. Collectively, while the two commercially available ELISAs perform equivalently, neither should be used independently of clinical evaluation to diagnose strongyloidiasis.
C1 [Anderson, Neil W.; Klein, Diane M.; Dornink, Sarina M.; Jespersen, Deborah J.; Theel, Elitza S.] Mayo Clin, Div Clin Microbiol, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Kubofcik, Joseph; Nutman, Thomas B.] NIH, Clin Parasitol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Merrigan, Stephen D.; Couturier, Marc Roger] Inst Clin & Expt Pathol, ARUP Labs, Salt Lake City, UT USA.
[Couturier, Marc Roger] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
RP Theel, ES (reprint author), Mayo Clin, Div Clin Microbiol, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
EM theel.elitza@mayo.edu
NR 22
TC 10
Z9 10
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD MAY
PY 2014
VL 21
IS 5
BP 732
EP 736
DI 10.1128/CVI.00041-14
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AJ0NU
UT WOS:000337352300017
PM 24648484
ER
PT J
AU O'Donnell, CD
Wright, A
Vogel, L
Boonnak, K
Treanor, JJ
Subbarao, K
AF O'Donnell, Christopher D.
Wright, Amber
Vogel, Leatrice
Boonnak, Kobporn
Treanor, John J.
Subbarao, Kanta
TI Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not
Exhibit Evidence of Original Antigenic Sin after Infection or
Vaccination with the 2009 Pandemic H1N1 Influenza Virus
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID ANTIBODY-RESPONSES; PROTECTIVE IMMUNITY; CROSS-PROTECTION; MICE;
VACCINES; HEMAGGLUTININ
AB The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.
C1 [O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Subbarao, Kanta] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
[Treanor, John J.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU NIH, NIAID
FX This research was supported in part by the Intramural Research Program
of the NIH, NIAID.
NR 55
TC 2
Z9 3
U1 4
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD MAY
PY 2014
VL 21
IS 5
BP 737
EP 746
DI 10.1128/CVI.00790-13
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AJ0NU
UT WOS:000337352300018
PM 24648486
ER
PT J
AU Paris, R
Kuschner, RA
Binn, L
Thomas, SJ
Colloca, S
Nicosia, A
Cortese, R
Bailer, RT
Sullivan, N
Koup, RA
AF Paris, Robert
Kuschner, Robert A.
Binn, Leonard
Thomas, Stephen J.
Colloca, Stefano
Nicosia, Alfredo
Cortese, Riccardo
Bailer, Robert T.
Sullivan, Nancy
Koup, Richard A.
TI Adenovirus Type 4 and 7 Vaccination or Adenovirus Type 4 Respiratory
Infection Elicits Minimal Cross-Reactive Antibody Responses to Nonhuman
Adenovirus Vaccine Vectors
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID NEUTRALIZING ANTIBODIES; HIV-1 VACCINE; PREEXISTING IMMUNITY; MILITARY
TRAINEES; DOUBLE-BLIND; IMMUNOGENICITY; IMMUNIZATION; EFFICACY; SAFETY;
CANDIDATE
AB Antivector immunity may limit the immunogenicity of adenovirus vector vaccines. We tested sera from individuals immunized with adenovirus type 4 and 7 (Ad4 and Ad7, respectively) vaccine or naturally infected with Ad4 for their ability to neutralize a panel of E1-deleted human and chimpanzee adenoviruses (ChAd). Small statistically significant increases in titers to ChAd63, ChAd3, human Ad35, and human Ad5 were observed. Neutralizing antibodies elicited by Ad4 infection or immunization results in a small amount of adenovirus cross-reactivity.
C1 [Paris, Robert] Walter Reed Army Inst Res, US Mil Malaria Res Program, Silver Spring, MD USA.
[Kuschner, Robert A.; Binn, Leonard; Thomas, Stephen J.] Walter Reed Army Inst Res, Viral Dis Branch, Silver Spring, MD USA.
[Colloca, Stefano; Nicosia, Alfredo; Cortese, Riccardo] Okairos, Rome, Italy.
[Nicosia, Alfredo; Cortese, Riccardo] CEINGE, Naples, Italy.
[Nicosia, Alfredo] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy.
[Bailer, Robert T.; Sullivan, Nancy; Koup, Richard A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rkoup@mail.nih.gov
FU Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases, National Institutes of Health.
NR 26
TC 7
Z9 7
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
EI 1556-679X
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD MAY
PY 2014
VL 21
IS 5
BP 783
EP 786
DI 10.1128/CVI.00011-14
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AJ0NU
UT WOS:000337352300024
PM 24623627
ER
PT J
AU Remais, JV
Hess, JJ
Ebi, KL
Markandya, A
Balbus, JM
Wilkinson, P
Haines, A
Chalabi, Z
AF Remais, Justin V.
Hess, Jeremy J.
Ebi, Kristie L.
Markandya, Anil
Balbus, John M.
Wilkinson, Paul
Haines, Andy
Chalabi, Zaid
TI Estimating the Health Effects of Greenhouse Gas Mitigation Strategies:
Addressing Parametric, Model, and Valuation Challenges
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
ID CLIMATE-CHANGE MITIGATION; AIR-POLLUTION; INTEGRATED ASSESSMENT;
CO-BENEFITS; UNITED-STATES; MEXICO-CITY; UNCERTAINTY; ADAPTATION;
IMPACTS; COSTS
AB Background: Policy decisions regarding climate change mitigation are increasingly incorporating the beneficial and adverse health impacts of greenhouse gas emission reduction strategies. Studies of such co-benefits and co-harms involve modeling approaches requiring a range of analytic decisions that affect the model output.
Objective: Our objective was to assess analytic decisions regarding model framework, structure, choice of parameters, and handling of uncertainty when modeling health co-benefits, and to make recommendations for improvements that could increase policy uptake.
Methods: We describe the assumptions and analytic decisions underlying models of mitigation co-benefits, examining their effects on modeling outputs, and consider tools for quantifying uncertainty.
Discussion: There is considerable variation in approaches to valuation metrics, discounting methods, uncertainty characterization and propagation, and assessment of low-probability/high-impact events. There is also variable inclusion of adverse impacts of mitigation policies, and limited extension of modeling domains to include implementation considerations. Going forward, co-benefits modeling efforts should be carried out in collaboration with policy makers; these efforts should include the full range of positive and negative impacts and critical uncertainties, as well as a range of discount rates, and should explicitly characterize uncertainty. We make recommendations to improve the rigor and consistency of modeling of health co-benefits.
Conclusion: Modeling health co-benefits requires systematic consideration of the suitability of model assumptions, of what should be included and excluded from the model framework, and how uncertainty should be treated. Increased attention to these and other analytic decisions has the potential to increase the policy relevance and application of co-benefits modeling studies, potentially helping policy makers to maximize mitigation potential while simultaneously improving health.
C1 [Remais, Justin V.; Hess, Jeremy J.] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA.
[Hess, Jeremy J.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA 30322 USA.
[Ebi, Kristie L.] ClimAdapt LLC, Los Altos, CA USA.
[Markandya, Anil] Basque Ctr Climate Change, Bilbao, Spain.
[Balbus, John M.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Wilkinson, Paul; Haines, Andy; Chalabi, Zaid] Univ London London Sch Hyg & Trop Med, Fac Publ Hlth & Policy, Dept Social & Environm Hlth Res, London WC1E 7HT, England.
RP Remais, JV (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA.
EM justin.remais@emory.edu
RI Markandya, Anil /K-9381-2013; Azkarate, Ainhoa/K-9087-2013
OI Azkarate, Ainhoa/0000-0003-0471-3094
FU National Institute for Allergy and Infectious Disease [K01AI091864];
National Institutes of Health (NIH)/National Science Foundation Ecology
of Infectious Disease Program [0622743]; Emory Global Health Institute
Faculty Distinction Fund; LIFE+ programme; European Commission's
FX J. V. R. was supported by the National Institute for Allergy and
Infectious Disease (grant K01AI091864), the National Institutes of
Health (NIH)/National Science Foundation Ecology of Infectious Disease
Program (grant 0622743), and the Emory Global Health Institute Faculty
Distinction Fund. A.M. was supported by the LIFE+ programme, the
European Commission's funding instrument for the environment.
NR 109
TC 9
Z9 9
U1 11
U2 30
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2014
VL 122
IS 5
BP 447
EP 455
DI 10.1289/ehp.1306744
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AJ3ZC
UT WOS:000337606300013
PM 24583270
ER
PT J
AU Wang, Y
Rogan, WJ
Chen, PC
Lien, GW
Chen, HY
Tseng, YC
Longnecker, MP
Wang, SL
AF Wang, Yan
Rogan, Walter J.
Chen, Pau-Chung
Lien, Guang-Wen
Chen, Hsiao-Yen
Tseng, Ying-Chih
Longnecker, Matthew P.
Wang, Shu-Li
TI Association between Maternal Serum Perfluoroalkyl Substances during
Pregnancy and Maternal and Cord Thyroid Hormones: Taiwan Maternal and
Infant Cohort Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID PERFLUORINATED FATTY-ACIDS; CARBON-CHAIN LENGTH; PERFLUOROOCTANE
SULFONATE; POLYFLUOROALKYL CHEMICALS; PLACENTAL-TRANSFER; EXPOSURE;
FETAL; RATS; HYPOTHYROIDISM; ELIMINATION
AB Background: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment.
Objectives: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates.
Methods: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models.
Results: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T-4) and total T4 levels. For example, we estimated that maternal free T-4 levels decreased 0.019 ng/dL (95% CI: -0.028, -0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T-3) and total T-4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T-3.
Conclusions: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses.
C1 [Wang, Yan; Rogan, Walter J.; Longnecker, Matthew P.; Wang, Shu-Li] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Chen, Pau-Chung; Lien, Guang-Wen] Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei 10764, Taiwan.
[Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Dept Publ Hlth, Taipei 10764, Taiwan.
[Chen, Pau-Chung] Natl Taiwan Univ, Coll Publ Hlth, Dept Environm & Occupat Med, Taipei 10764, Taiwan.
[Chen, Pau-Chung] Natl Taiwan Univ Hosp, Taipei, Taiwan.
[Chen, Hsiao-Yen; Wang, Shu-Li] Natl Hlth Res Inst, Div Environm Hlth & Occupat Med, Miaoli, Taiwan.
[Tseng, Ying-Chih] Hsinchu Cathay Gen Hosp, Dept Obstet & Gynecol, Hsinchu, Taiwan.
[Wang, Shu-Li] China Med Univ, Coll Publ Hlth, Dept Publ Hlth, Taichung, Taiwan.
RP Wang, SL (reprint author), Natl Hlth Res Inst, Div Environm Hlth & Occupat Med, 35 Keyan Rd, Zhunan 350, Miaoli County, Taiwan.
EM slwang@nhri.org.tw
RI Wang, Shu-Li/C-1367-2010; Rogan, Walter/I-6034-2012;
OI Rogan, Walter/0000-0002-9302-0160; Longnecker,
Matthew/0000-0001-6073-5322; Chen, Pau-Chung/0000-0002-6242-5974
NR 38
TC 24
Z9 25
U1 7
U2 35
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2014
VL 122
IS 5
BP 529
EP 534
DI 10.1289/ehp.1306925
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AJ3ZC
UT WOS:000337606300024
PM 24577800
ER
PT J
AU Golding, J
Steer, CD
Lowery, T
Jones, R
Hibbeln, JR
AF Golding, Jean
Steer, Colin D.
Lowery, Tony
Jones, Robert
Hibbeln, Joseph R.
TI Fish Consumption and Blood Mercury Levels: Golding et al. Respond
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
ID UK TOTAL DIET
C1 [Golding, Jean; Steer, Colin D.] Univ Bristol, Ctr Child & Adolescent Hlth, Bristol, RI 02809 USA.
[Lowery, Tony] Natl Ocean & Atmospher Adm, Natl Marine Fisheries Serv, Natl Seafood Inspect Lab, Pascagoula, MS USA.
[Jones, Robert] Ctr Dis Control & Prevent, Inorgan & Radiat Analyt Toxicol Branch, Atlanta, GA USA.
[Hibbeln, Joseph R.] NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Golding, J (reprint author), Univ Bristol, Ctr Child & Adolescent Hlth, Bristol, RI 02809 USA.
EM Jean.Golding@bristol.ac.uk
OI Golding, Jean/0000-0003-2826-3307
NR 3
TC 0
Z9 0
U1 0
U2 10
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAY
PY 2014
VL 122
IS 5
BP A120
EP A121
DI 10.1289/ehp.1307997R
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AJ3ZC
UT WOS:000337606300004
PM 24787643
ER
PT J
AU Warnke, C
von Geldern, G
Markwerth, P
Dehmel, T
Hoepner, R
Gold, R
Pawlita, M
Kumpfel, T
Maurer, M
Stangel, M
Wegner, F
Hohlfeld, R
Straeten, V
Limmroth, V
Weber, T
Hermsen, D
Kleinschnitz, C
Hartung, HP
Wattjes, MP
Svenningson, A
Major, E
Olsson, T
Kieseier, BC
Adams, O
AF Warnke, C.
von Geldern, G.
Markwerth, P.
Dehmel, T.
Hoepner, R.
Gold, R.
Pawlita, M.
Kuempfel, T.
Maeurer, M.
Stangel, M.
Wegner, F.
Hohlfeld, R.
Straeten, V.
Limmroth, V.
Weber, T.
Hermsen, D.
Kleinschnitz, C.
Hartung, H. -P.
Wattjes, M. P.
Svenningson, A.
Major, E.
Olsson, T.
Kieseier, B. C.
Adams, O.
TI The CSF JCV antibody index for diagnosis of natalizumab-associated PML
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT Joint Congress of European Neurology
CY MAY 31-JUN 03, 2014
CL Istanbul, TURKEY
SP European Federat Neurol Soc
C1 [Warnke, C.; Markwerth, P.; Dehmel, T.; Hermsen, D.; Hartung, H. -P.; Kieseier, B. C.; Adams, O.] Univ Dusseldorf, Dusseldorf, Germany.
[von Geldern, G.; Major, E.] NINDS, Bethesda, MD 20892 USA.
[Hoepner, R.; Gold, R.] Ruhr Univ Bochum, St Josef Hosp, Bochum, Germany.
[Pawlita, M.] German Canc Res Ctr, Heidelberg, Germany.
[Kuempfel, T.; Hohlfeld, R.] Univ Munich, Munich, Germany.
[Maeurer, M.] Caritas Hosp, Bad Mergentheim, Germany.
[Stangel, M.; Wegner, F.] Hannover Med Sch MHH, Hannover, Germany.
[Straeten, V.] Johannes Wesling Hosp Minden, Minden, Germany.
[Limmroth, V.] Merheim Hosp, Cologne, Germany.
[Weber, T.] Marien Hosp, Hamburg, Germany.
[Kleinschnitz, C.] Univ Wurzburg, D-97070 Wurzburg, Germany.
[Wattjes, M. P.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Svenningson, A.] Umea Univ Hosp, S-90185 Umea, Sweden.
[Olsson, T.] Karolinska Inst, Stockholm, Sweden.
RI Waterboer, Tim/G-1252-2010
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD MAY
PY 2014
VL 21
SU 1
SI SI
MA OS2124
BP 59
EP 59
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AJ3JX
UT WOS:000337563600117
ER
PT J
AU Bilic, E
Grkovic, L
Pulanic, D
Seiwerth, RS
Bilic, E
Nemet, D
Pavletic, SZ
AF Bilic, E.
Grkovic, L.
Pulanic, D.
Seiwerth, R. Serventi
Bilic, E.
Nemet, D.
Pavletic, S. Z.
TI Small fiber neuropathy in patients with chronic graft-versus-host
disease after allogeneic hematopoietic stem cell transplantation -
preliminary results of a prospective study
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT Joint Congress of European Neurology
CY MAY 31-JUN 03, 2014
CL Istanbul, TURKEY
SP European Federat Neurol Soc
C1 [Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Neurol, Zagreb 41001, Croatia.
[Grkovic, L.; Pulanic, D.; Seiwerth, R. Serventi; Nemet, D.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Hematol, Zagreb 41001, Croatia.
[Bilic, E.] Univ Zagreb, Sch Med, Clin Hosp Ctr Zagreb, Dept Pediat Hematol & Oncol, Zagreb 41001, Croatia.
[Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD MAY
PY 2014
VL 21
SU 1
SI SI
MA PP1251
BP 469
EP 469
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AJ3JX
UT WOS:000337563601136
ER
PT J
AU Vural, A
Johnson, J
Singleton, A
Temucin, CM
AF Vural, A.
Johnson, J.
Singleton, A.
Temucin, C. M.
TI Adult-onset case of Brown-Vialetto-Van-Laere syndrome with SLC52A3
mutation
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Meeting Abstract
CT Joint Congress of European Neurology
CY MAY 31-JUN 03, 2014
CL Istanbul, TURKEY
SP European Federat Neurol Soc
C1 [Vural, A.] Besni Govt Hosp, Dept Neurol, Adiyaman, Turkey.
[Johnson, J.; Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Temucin, C. M.] Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey.
RI Singleton, Andrew/C-3010-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD MAY
PY 2014
VL 21
SU 1
SI SI
MA PP4091
BP 657
EP 657
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AJ3JX
UT WOS:000337563601412
ER
PT J
AU Burkey, MD
Weiser, SD
Fehmie, D
Alamo-Talisuna, S
Sunday, P
Nannyunja, J
Reynolds, SJ
Chang, LW
AF Burkey, Matthew D.
Weiser, Sheri D.
Fehmie, Desiree
Alamo-Talisuna, Stella
Sunday, Pamella
Nannyunja, Joy
Reynolds, Steven J.
Chang, Larry W.
TI Socioeconomic Determinants of Mortality in HIV: Evidence From a Clinical
Cohort in Uganda
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; socioeconomic status; lost to follow-up; mortality
ID SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY PROGRAM; SOUTH-AFRICA;
FUNDAMENTAL CAUSES; SOCIAL CONDITIONS; INFECTED PATIENTS; RISK-FACTOR;
FOLLOW-UP; SURVIVAL; HEALTH
AB Objective: To delineate the association between baseline socioeconomic status (SES) indicators and mortality and lost to follow-up (LTFU) in a cohort of HIV-infected individuals enrolled in antiretroviral therapy (ART) in urban Uganda.
Design: Retrospective cohort study nested in an antiretroviral clinic-based cohort.
Methods: SES indicators including education, employment status, and a standardized wealth index, and other demographic and clinical variables were assessed at baseline among ART-treated patients in a clinic-based cohort in Kampala, Uganda. Confirmed mortality (primary outcome) and LTFU (secondary outcome) were actively ascertained over a 4-year follow-up period from 2005 to 2009.
Results: Among 1763 adults [70.5% female; mean age, 36.2 years (SD = 8.4)] enrolled in ART, 14.4% (n = 253) were confirmed dead and 19.7% (n = 346) were LTFU at 4-year follow-up. No formal education [adjusted odds ratio (AOR) 1.76; 95% confidence interval (CI): 1.19 to 2.59], having fewer than 6 dependents (AOR 1.39; 95% CI: 1.04 to 1.86), unemployment (AOR 1.98; 95% CI: 1.48 to 2.66), and housing tenure index score (a component of the wealth index) (AOR 1.11; 95% CI: 1.00 to 1.23) were significantly associated with confirmed mortality at 4 years. SES indicators were not associated with LTFU at 4 years.
Conclusions: Baseline SES indicators, including education, number of dependents, employment status, and components of a standard wealth index may indicate long-term vulnerability to mortality in patients with HIV/AIDS, despite uniform access to ART. Future studies delineating the pathways through which poverty and limited assets affect clinical outcomes may lead to more effective HIV interventions in low-resource settings.
C1 [Burkey, Matthew D.] Johns Hopkins Univ Hosp, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA.
[Weiser, Sheri D.] Univ Calif San Francisco, Div HIV AIDS, San Francisco, CA 94143 USA.
[Weiser, Sheri D.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA.
[Fehmie, Desiree] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA.
[Alamo-Talisuna, Stella; Sunday, Pamella; Nannyunja, Joy] Reach Out Mbuya, Kampala, Uganda.
[Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Chang, Larry W.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA.
[Chang, Larry W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Burkey, MD (reprint author), Johns Hopkins Univ Hosp, 1800 Orleans St,Bloomberg 12352, Baltimore, MD 21287 USA.
EM mburkey1@jhmi.edu
FU Johns Hopkins Center for Global Health; National Institute of Mental
Health [5K23MH086338, R01MH095683]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Burke Family Foundation
FX M.D.B. was supported by a grant from the Johns Hopkins Center for Global
Health to conduct this study. L. W. C. was supported by the National
Institute of Mental Health (5K23MH086338). S.J.R. was supported by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. S. D. W was
supported by the National Institute of Mental Health (R01MH095683) and
the Burke Family Foundation.
NR 38
TC 6
Z9 6
U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD MAY 1
PY 2014
VL 66
IS 1
BP 41
EP 47
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AJ4YF
UT WOS:000337685400011
PM 24378727
ER
PT J
AU Abate-Daga, D
Beard, RE
Muranski, P
Lu, YC
Arons, E
Alexander, TA
Steinberg, S
Ho, M
Robbins, PF
Morgan, RA
Rosenberg, SA
AF Abate-Daga, Daniel
Beard, Rachel E.
Muranski, Pawel
Lu, Yong-Chen
Arons, Evgeny
Alexander, Theresa A.
Steinberg, Seth
Ho, Mitchell
Robbins, Paul F.
Morgan, Richard A.
Rosenberg, Steven A.
TI Transcriptomic Analysis of Human Melanoma Lesions Resected for TIL
Production Reveals the Presence of B Cells in Association With T
Lymphocytes
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Abate-Daga, Daniel; Beard, Rachel E.; Muranski, Pawel; Lu, Yong-Chen; Alexander, Theresa A.; Robbins, Paul F.; Morgan, Richard A.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Arons, Evgeny; Ho, Mitchell] NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
[Steinberg, Seth] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Morgan, Richard A.] BlueBird Bio, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 439
BP S168
EP S169
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300434
ER
PT J
AU Assadipour, Y
Xu, H
Black, MA
Rosenberg, SA
Kochenderfer, JN
Feldman, SA
AF Assadipour, Yasmine
Xu, Hui
Black, Mary A.
Rosenberg, Steven A.
Kochenderfer, James N.
Feldman, Steven A.
TI Increasing Adoptive Cell Therapy Safety Through the Use of an Inducible
Caspase 9
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Assadipour, Yasmine; Xu, Hui; Black, Mary A.; Rosenberg, Steven A.; Feldman, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 435
BP S167
EP S167
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300430
ER
PT J
AU Bauer, TR
Tuschong, LM
Russell, DW
Hickstein, DD
AF Bauer, Thomas R., Jr.
Tuschong, Laura M.
Russell, David W.
Hickstein, Dennis D.
TI Long-Term Correction of Canine Leukocyte Adhesion Deficiency With Foamy
Viral Vector-Mediated Gene Therapy Using Reduced Intensity Busulfan
Conditioning
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Bauer, Thomas R., Jr.; Tuschong, Laura M.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Russell, David W.] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 459
BP S176
EP S176
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300454
ER
PT J
AU Bolduc, V
Zou, YQ
Lindow, M
Ko, D
Obad, S
Bonnemann, CG
AF Bolduc, Veronique
Zou, Yaqun
Lindow, Morten
Ko, Dayoung
Obad, Susanna
Boennemann, Carsten G.
TI Allele-Specific Silencing of a Dominant-Negative Mutation Using siRNA or
LNA Antisense Oligonucleotides Alleviates the Phenotype in a Cellular
Model of Ullrich Congenital Muscular Dystrophy
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Bolduc, Veronique; Zou, Yaqun; Ko, Dayoung; Boennemann, Carsten G.] NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lindow, Morten; Obad, Susanna] Santaris Pharma AS, Horsholm, Denmark.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 143
BP S54
EP S54
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300143
ER
PT J
AU Byrd, TT
Fousek, K
Aviles-Padilla, K
Bielamowicz, K
Gottschalk, S
St Croix, B
Fletcher, B
Hegde, M
Ahmed, N
AF Byrd, Tiara T.
Fousek, Kristen
Aviles-Padilla, Kevin
Bielamowicz, Kevin
Gottschalk, Stephen
St Croix, Bradley
Fletcher, Bradley
Hegde, Meenakshi
Ahmed, Nabil
TI A Single Chimeric Antigen Receptor Simultaneously Targets the Tumor
Endothelium as Well as the Tumor Cells in Glioblastoma
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Byrd, Tiara T.; Fousek, Kristen; Gottschalk, Stephen; Ahmed, Nabil] Baylor Coll Med, Houston, TX 77030 USA.
[Byrd, Tiara T.; Fousek, Kristen; Aviles-Padilla, Kevin; Bielamowicz, Kevin; Gottschalk, Stephen; Hegde, Meenakshi; Ahmed, Nabil] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Byrd, Tiara T.; Fousek, Kristen; Aviles-Padilla, Kevin; Bielamowicz, Kevin; Gottschalk, Stephen; Hegde, Meenakshi; Ahmed, Nabil] Texas Childrens Hosp, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
[Fletcher, Bradley] Univ Florida, Gainesville, FL USA.
[St Croix, Bradley] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 160
BP S60
EP S60
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300160
ER
PT J
AU Cash, A
Chang, Z
Ichwan, B
Metais, JY
Dunbar, CE
Larochelle, A
AF Cash, Ayla
Chang, Zanetta
Ichwan, Brian
Metais, Jean-Yves
Dunbar, Cynthia E.
Larochelle, Andre
TI Culture of Mobilized Rhesus Macaque CD34+Cells in Hypoxic Conditions
Does Not Improve Lentiviral Transduction Efficiency in Long-Term
Repopulating Hematopoietic Stem Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Cash, Ayla; Chang, Zanetta; Ichwan, Brian; Metais, Jean-Yves; Dunbar, Cynthia E.; Larochelle, Andre] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 690
BP S267
EP S267
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300681
ER
PT J
AU Chandler, RJ
Ashok, AA
Varshney, GK
Lafave, MC
Wu, WW
Hoffmann, V
Elkahloun, AG
Burgess, SM
Venditti, CP
AF Chandler, Randy J.
Ashok, Adi A.
Varshney, Gaurav K.
Lafave, Matthew C.
Wu, Weiwei
Hoffmann, Victoria
Elkahloun, Abdel G.
Burgess, Shawn M.
Venditti, Charles P.
TI Genomic Analyses Define a Common Integration Site in Hepatocellular
Carcinoma Caused By Therapeutic AAV Gene Delivery: A Mouse-Specific
Phenomenon or New Safety Challenge for Human Gene Therapy?
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Chandler, Randy J.; Ashok, Adi A.; Varshney, Gaurav K.; Lafave, Matthew C.; Wu, Weiwei; Hoffmann, Victoria; Elkahloun, Abdel G.; Burgess, Shawn M.; Venditti, Charles P.] Natl Human Genome Inst, NIH, Bethesda, MD USA.
RI Varshney, Gaurav/L-5261-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 242
BP S92
EP S92
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300242
ER
PT J
AU Cohen, CJ
Rosenberg, SA
Robbins, PF
AF Cohen, Cyrille J.
Rosenberg, Steven A.
Robbins, Paul F.
TI Using an MHC/Tetramer-Driven Approach To Detect and Exploit Neo-Antigen
Specific T-Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Cohen, Cyrille J.] Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, Ramat Gan, Israel.
[Cohen, Cyrille J.; Rosenberg, Steven A.; Robbins, Paul F.] NCI, Surg Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 633
BP S245
EP S245
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300627
ER
PT J
AU De Ravin, SS
Moir, S
Theobald, N
Lee, J
Wu, XL
Choi, U
Kang, E
Gray, JT
Sorrentino, BP
Malech, HL
AF De Ravin, Suk See
Moir, Susan
Theobald, Narda
Lee, Janet
Wu, Xiaolin
Choi, Uimook
Kang, Elizabeth
Gray, John T.
Sorrentino, Brian P.
Malech, Harry L.
TI Lentivector Gene Therapy with Non-Myeloablative Conditioning Restores
IgG Production in Young Adults with SCID-X1
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [De Ravin, Suk See; Moir, Susan; Theobald, Narda; Lee, Janet; Choi, Uimook; Kang, Elizabeth; Malech, Harry L.] NIAID, Bethesda, MD 20892 USA.
[Wu, Xiaolin] Frederick Natl Lab Canc Res, Frederick, MD USA.
[Gray, John T.; Sorrentino, Brian P.] SJCRH, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
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 MAY
PY 2014
VL 22
SU 1
MA 278
BP S106
EP S107
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300278
ER
PT J
AU Frank, JA
Tebebi, P
Nguyen, B
Kim, S
Burks, S
AF Frank, Joseph A.
Tebebi, Pamela
Nguyen, Ben
Kim, Sage
Burks, Scott
TI Cyclo-Oxygenase or TNF alpha Inhibitors Interferes With the
Mechanotransductive Effects of Pulsed Focused Ultrasound By Blunting
Enhanced Homing of Mesenchymal Stem Cell
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Frank, Joseph A.; Tebebi, Pamela; Nguyen, Ben; Kim, Sage; Burks, Scott] NIH, Frank Lab, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 473
BP S181
EP S182
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300468
ER
PT J
AU Fujita, A
Tisdale, J
Uchida, N
AF Fujita, Atsushi
Tisdale, John
Uchida, Naoya
TI Mycoplasma Contamination Can Be Caused By Frozen Lentiviral Vectors in
iPS Cell Generation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Fujita, Atsushi; Tisdale, John; Uchida, Naoya] NHLBI NIDDK, MCHB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 218
BP S83
EP S83
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300218
ER
PT J
AU Glait-Santar, C
Feng, XM
Chen, JC
Desmond, R
Mizukawa, B
Mulloy, JC
Young, NS
Dunbar, CE
AF Glait-Santar, Chen
Feng, Xingmin
Chen, Jichun
Desmond, Ronan
Mizukawa, Benjamin
Mulloy, James C.
Young, Neal S.
Dunbar, Cynthia E.
TI Functional Niche Competition Between Normal and Leukemic Stem Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Glait-Santar, Chen; Feng, Xingmin; Chen, Jichun; Desmond, Ronan; Young, Neal S.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Mizukawa, Benjamin; Mulloy, James C.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 688
BP S266
EP S266
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300679
ER
PT J
AU Haddad, MR
Choi, EY
Kaler, SG
AF Haddad, Marie Reine
Choi, Eun-Young
Kaler, Stephen G.
TI AAVrh10-ATP7A Administration to the Cerebrospinal Fluid, in Combination
with Subcutaneous Copper, Normalizes Neurological Outcomes in a Mouse
Model of Menkes Disease
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Haddad, Marie Reine; Choi, Eun-Young; Kaler, Stephen G.] NICHD, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 261
BP S99
EP S100
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300261
ER
PT J
AU Hanley, PJ
Nikiforow, S
Heslop, HE
Shpall, EJ
Barrett, J
Rodgers, J
Bollard, C
AF Hanley, Patrick J.
Nikiforow, Sarah
Heslop, Helen E.
Shpall, E. J.
Barrett, John
Rodgers, John
Bollard, Catherine
TI CMV-Specific T Cells Derived From the Naive T Cell Population To Treat
Transplant Recipients
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Hanley, Patrick J.; Bollard, Catherine] Childrens Hlth Syst, Program Cell Enhancement & Technol Immunotherapy, Washington, DC USA.
[Nikiforow, Sarah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Heslop, Helen E.; Rodgers, John] Baylor Coll Med, CAGT, Houston, TX 77030 USA.
[Barrett, John] NHLBI, NIH, Bethesda, MD 20892 USA.
[Shpall, E. J.] MD Anderson, Stem Cell Transplantat, Houston, TX USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 693
BP S268
EP S268
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300684
ER
PT J
AU Hjelm, BE
Grunseich, C
Narwani, K
Shelley, B
Shi, YJ
Avalos, P
Mooney, M
Gowing, G
Fischbeck, KH
Pierson, TM
AF Hjelm, Brooke E.
Grunseich, Christopher
Narwani, Kavita
Shelley, Brandon
Shi, Yijun
Avalos, Pablo
Mooney, Michael
Gowing, Genevieve
Fischbeck, Kenneth H.
Pierson, Tyler M.
TI Mifepristone-Inducible Gene Expression of Target Genes in Murine and
Human Neural Progenitor Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Hjelm, Brooke E.; Narwani, Kavita; Shelley, Brandon; Avalos, Pablo; Gowing, Genevieve; Pierson, Tyler M.] Cedars Sinai Med Ctr, RMI, Los Angeles, CA 90048 USA.
[Grunseich, Christopher; Shi, Yijun; Mooney, Michael; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 719
BP S277
EP S278
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300710
ER
PT J
AU Jung, M
Winkler, T
Donaires, FS
Hong, SG
Hsu, AP
Hickstein, DD
Holland, SM
Dunbar, CE
AF Jung, Moonjung
Winkler, Thomas
Donaires, Flavia S.
Hong, So Gun
Hsu, Amy P.
Hickstein, Dennis D.
Holland, Steven M.
Dunbar, Cynthia E.
TI Induced Pluripotent Stem Cells from a Patient with GATA2 Deficiency
Display a Block in Hematopoietic Differentiation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Jung, Moonjung; Winkler, Thomas; Donaires, Flavia S.; Hong, So Gun; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Hsu, Amy P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hickstein, Dennis D.] NCI, Dept Expt Transplantat & Immunol, NIH, Bethesda, MD 20892 USA.
RI Sacilotto Donaires, Flavia/R-9719-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 207
BP S79
EP S79
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300207
ER
PT J
AU Kochenderfer, JN
Kassim, SH
Somerville, R
Dudley, ME
Carpenter, RO
Lu, L
Feldman, SA
Morton, KE
Toomey, MA
Rosenberg, SA
AF Kochenderfer, James N.
Kassim, Sadik H.
Somerville, Robert
Dudley, Mark E.
Carpenter, Robert O.
Lu, Lily
Feldman, Steven A.
Morton, Kathleen E.
Toomey, Mary Ann
Rosenberg, Steven A.
TI Treatment of Chemotherapy-Refractory B-Cell Malignancies with Anti-CD19
Chimeric Antigen Receptor T Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Kochenderfer, James N.; Carpenter, Robert O.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Kassim, Sadik H.; Somerville, Robert; Dudley, Mark E.; Lu, Lily; Feldman, Steven A.; Morton, Kathleen E.; Toomey, Mary Ann; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 765
BP S295
EP S295
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300756
ER
PT J
AU Kouprina, N
Larionov, V
AF Kouprina, Natalay
Larionov, Vladimir
TI Human Artificial Chromosomes or HAC-Based Gene Delivery Vectors for
Biomedicine and Biotechnology
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Kouprina, Natalay; Larionov, Vladimir] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY
PY 2014
VL 22
SU 1
MA 95
BP S36
EP S36
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300095
ER
PT J
AU Lynn, RC
Poussin, M
Low, PS
Dimitrov, DS
Powell, DJ
AF Lynn, Rachel C.
Poussin, Mathilde
Low, Phillip S.
Dimitrov, Dimiter S.
Powell, Daniel J., Jr.
TI FR beta-Directed CAR T Cell Therapy for AML Can Be Enhanced By ATRA
Co-Treatment
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Lynn, Rachel C.; Poussin, Mathilde; Powell, Daniel J., Jr.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, OCRC,Abramson Canc Ctr, Philadelphia, PA USA.
[Low, Phillip S.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCR Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 159
BP S60
EP S60
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300159
ER
PT J
AU Mao, L
Shen, FX
Choi, EJ
Lawton, MT
Scaria, A
Colosi, P
Pechan, P
Wu, ZJ
Su, H
AF Mao, Lei
Shen, Fanxia
Choi, Eun-Jung
Lawton, Michael T.
Scaria, Abraham
Colosi, Peter
Pechan, Peter
Wu, Zhijian
Su, Hua
TI AAV-sFLT Inhibits and Reverses Brain Arteriovenous Malformation
Phenotype in Mice
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Mao, Lei; Shen, Fanxia; Choi, Eun-Jung; Su, Hua] Univ Calif San Francisco, Ctr Cerebrovasc Res, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Lawton, Michael T.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Scaria, Abraham; Pechan, Peter] Sanofi Genzyme R&D Ctr, Framingham, MA USA.
[Colosi, Peter; Wu, Zhijian] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 267
BP S102
EP S102
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300267
ER
PT J
AU Mattoo, AR
Thorgeirsson, SS
Jessup, JM
AF Mattoo, Abid R.
Thorgeirsson, Snorri S.
Jessup, J. M.
TI Lessons Learned From TALEN Knockout of NANOG in Colorectal Carcinoma
(CRC) Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Mattoo, Abid R.; Thorgeirsson, Snorri S.; Jessup, J. M.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 561
BP S217
EP S218
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300556
ER
PT J
AU Mattoo, AR
Korokhov, N
Jessup, JM
AF Mattoo, Abid R.
Korokhov, Nikolay
Jessup, J. M.
TI Lentiviral Delivered shRNA Inhibition of NANOGP8 or NANOG Activates the
Intrinsic Pathway of Apoptosis In Vivo and In Vitro
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Mattoo, Abid R.; Korokhov, Nikolay; Jessup, J. M.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 455
BP S174
EP S174
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300450
ER
PT J
AU Mookherjee, S
Colosi, P
Hiriyanna, S
Kaneshiro, K
Li, LJ
Qian, HH
Li, TS
Khanna, H
Swaroop, A
Wu, ZJ
AF Mookherjee, Suddhasil
Colosi, Peter
Hiriyanna, Suja
Kaneshiro, Kayleigh
Li, Linjing
Qian, Haohua
Li, Tiansen
Khanna, Hemant
Swaroop, Anand
Wu, Zhijian
TI A Long-Term Study of AAV Vector-Mediated Gene Therapy for X-linked
Retinitis Pigmentosa (XLRP) Due to RP2 Mutation
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Mookherjee, Suddhasil; Colosi, Peter; Hiriyanna, Suja; Kaneshiro, Kayleigh; Qian, Haohua; Li, Tiansen; Swaroop, Anand; Wu, Zhijian] NEI, NIH, Bethesda, MD 20892 USA.
[Li, Linjing; Khanna, Hemant] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 122
BP S46
EP S46
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300122
ER
PT J
AU Peterson, L
Burke, JD
Jagadeesh, GJ
Myung, S
Garrett, L
Pourebrahim, R
Davis, BR
Candotti, F
AF Peterson, Lisa
Burke, J. Douglas
Jagadeesh, G. Jaya
Myung, Sangho
Garrett, Lisa
Pourebrahim, Rasoul
Davis, Brian R.
Candotti, Fabio
TI Comparison of Gene Editing Strategies for Gene Correction of
Wiskott-Aldrich Syndrome in Mouse Embryonic Stem Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Peterson, Lisa] Walter Reed Natl Mil Med Ctr, Dept Neonatol, Bethesda, MD USA.
[Peterson, Lisa; Burke, J. Douglas; Jagadeesh, G. Jaya; Myung, Sangho; Candotti, Fabio] NIH, Bethesda, MD 20892 USA.
[Garrett, Lisa] NIH, Transgen Stem Cell Core, Bethesda, MD 20892 USA.
[Pourebrahim, Rasoul; Davis, Brian R.] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 558
BP S216
EP S217
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300553
ER
PT J
AU Richie, CT
Simons-Wires, EM
Trychta, KA
Harvey, BK
Henderson, MJ
AF Richie, Christopher T.
Simons-Wires, Emily M.
Trychta, Kathleen A.
Harvey, Brandon K.
Henderson, Mark J.
TI SERCaMP: A Secreted Reporter Protein to Monitor Perturbations in
Endoplasmic Reticulum Calcium Homeostasis
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Richie, Christopher T.; Simons-Wires, Emily M.; Trychta, Kathleen A.; Harvey, Brandon K.; Henderson, Mark J.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 370
BP S141
EP S141
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300368
ER
PT J
AU Senac, JS
Venditti, CP
AF Senac, Julien S.
Venditti, Charles P.
TI In Vivo Interallelic Complementation Assay at the Mut Locus With
Adeno-Associated (AAV) Viral Gene Delivery
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Senac, Julien S.; Venditti, Charles P.] NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 361
BP S137
EP S138
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300359
ER
PT J
AU Shaw, KL
Sokolic, R
Davila, A
Silvin, C
Garabedian, E
de Oliveira, S
Barman, P
Brown, B
Carbonaro, D
Geiger, S
Mishra, S
Smogorzewska, M
Jagadeesh, J
Hershfield, MS
Wayne, A
Crooks, GM
Moore, T
Candotti, F
Kohn, DB
AF Shaw, Kit L.
Sokolic, Robert
Davila, Alejandra
Silvin, Christopher
Garabedian, Elizabeth
de Oliveira, Satiro
Barman, Provaboti
Brown, Berkley
Carbonaro, Denise
Geiger, Sabine
Mishra, Suparna
Smogorzewska, Monika
Jagadeesh, Jayashree
Hershfield, Michael S.
Wayne, Alan
Crooks, Gay M.
Moore, Theodore
Candotti, Fabio
Kohn, Donald B.
TI Phase II Clinical Trial of Gene Therapy for Adenosine
Deaminase-Deficient Severe Combined Immune Deficiency (ADA-SCID)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Shaw, Kit L.; Davila, Alejandra; de Oliveira, Satiro; Barman, Provaboti; Brown, Berkley; Carbonaro, Denise; Geiger, Sabine; Mishra, Suparna; Crooks, Gay M.; Moore, Theodore; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Sokolic, Robert; Silvin, Christopher; Garabedian, Elizabeth; Jagadeesh, Jayashree; Wayne, Alan; Candotti, Fabio] NIH, Bethesda, MD 20892 USA.
[Smogorzewska, Monika] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Hershfield, Michael S.] Duke Univ, Durham, NC USA.
RI De Oliveira, Satiro/D-8860-2014
OI De Oliveira, Satiro/0000-0002-8181-7316
NR 0
TC 1
Z9 1
U1 1
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 279
BP S107
EP S107
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300279
ER
PT J
AU Sloan, JL
Manoli, I
Harrington, E
Chandler, RJ
Schneider, M
Calcedo, R
Wilson, JM
Venditti, CP
AF Sloan, Jennifer L.
Manoli, Irini
Harrington, Elizabeth
Chandler, Randy J.
Schneider, Mark
Calcedo, Roberto
Wilson, James M.
Venditti, Charles P.
TI Neutralizing Antibodies Against AAV Capsids in Patients with Mut
Methylmalonic Acidemia (MMA)
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Sloan, Jennifer L.; Manoli, Irini; Harrington, Elizabeth; Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, NIH, Bethesda, MD 20892 USA.
[Schneider, Mark; Calcedo, Roberto; Wilson, James M.] Univ Penn, Dept Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 192
BP S73
EP S73
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300192
ER
PT J
AU Smith, JB
Lanitis, E
Dangaj, D
Flingai, S
Poussin, M
Xu, SW
Czerniecki, BJ
Li, YF
Robbins, PF
Powell, DJ
AF Smith, Jenessa B.
Lanitis, Evripidis
Dangaj, Denarda
Flingai, Seleeke
Poussin, Mathilde
Xu, Shuwen
Czerniecki, Brian J.
Li, Yong F.
Robbins, Paul F.
Powell, Daniel J.
TI A Human HER2-Specific TCR Confers Potent Anti-Tumor Effector Functions
in Genetically Engineered Primary Cytotoxic Lymphocytes
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Smith, Jenessa B.; Lanitis, Evripidis; Dangaj, Denarda; Flingai, Seleeke; Poussin, Mathilde; Powell, Daniel J.] Univ Penn, Dept Obstet & Gynecol, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA.
[Powell, Daniel J.] Univ Penn, Dept Pathol & Lab Med, Abramson Canc Ctr, Philadelphia, PA USA.
[Xu, Shuwen; Czerniecki, Brian J.] Univ Penn, Med Ctr, Dept Surg, Philadelphia, PA 19104 USA.
[Li, Yong F.; Robbins, Paul F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 429
BP S164
EP S165
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300424
ER
PT J
AU Uchida, N
Platner, C
Weitzel, RP
Bonifacino, A
Price, S
Krouse, A
Metzger, M
Donahue, R
Tisdale, J
AF Uchida, Naoya
Platner, Charlotte
Weitzel, R. Patrick
Bonifacino, Aylin
Price, Sandra
Krouse, Allen
Metzger, Mark
Donahue, Robert
Tisdale, John
TI Evaluation of Lentiviral Transduction Between Steady State Bone Marrow
CD34+Cells and Mobilized CD34+Cells in Rhesus Gene Therapy Model
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Uchida, Naoya; Platner, Charlotte; Weitzel, R. Patrick; Tisdale, John] NHLBI NIDDK, MCHB, NIH, Bethesda, MD USA.
[Bonifacino, Aylin; Price, Sandra; Krouse, Allen; Metzger, Mark; Donahue, Robert] NHLBI, Hematol Branch, NIH, Rockville, MD USA.
NR 0
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 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 548
BP S213
EP S213
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300543
ER
PT J
AU Valdmanis, PN
Gu, S
Lisowski, L
Jin, L
Chu, K
Zhang, FJ
Huang, Y
Kay, MA
AF Valdmanis, Paul N.
Gu, Shuo
Lisowski, Leszek
Jin, Lan
Chu, Kirk
Zhang, Feijie
Huang, Yong
Kay, Mark A.
TI Evaluating Competition of Delivered Small Hairpin RNAs with Endogenous
microRNAs for Safe Effective Gene Knockdown
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Valdmanis, Paul N.; Lisowski, Leszek; Chu, Kirk; Zhang, Feijie; Huang, Yong; Kay, Mark A.] Stanford Univ, Stanford, CA 94305 USA.
[Gu, Shuo; Jin, Lan] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
RI Gu, Shuo/K-5404-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 534
BP S208
EP S208
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300529
ER
PT J
AU Wu, ZJ
Hiriyanna, S
Qian, HH
Mookherjee, S
Kaneshiro, K
Campos, M
Gao, C
Fariss, R
Li, TS
Colosi, P
Swaroop, A
AF Wu, Zhijian
Hiriyanna, Suja
Qian, Haohua
Mookherjee, Suddhasil
Kaneshiro, Kayleigh
Campos, Maria
Gao, Chun
Fariss, Robert
Li, Tiansen
Colosi, Peter
Swaroop, Anand
TI Gene Therapy for X-Linked Retinitis Pigmentosa: A Long-Term Efficacy
Study in a Mouse Model of RPGR Deficiency
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Wu, Zhijian; Hiriyanna, Suja; Qian, Haohua; Mookherjee, Suddhasil; Kaneshiro, Kayleigh; Campos, Maria; Gao, Chun; Fariss, Robert; Li, Tiansen; Colosi, Peter; Swaroop, Anand] NEI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 537
BP S209
EP S209
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300532
ER
PT J
AU Xu, WQ
Blankenship, T
Eiden, MV
AF Xu, Wenqin
Blankenship, Tiffany
Eiden, Maribeth V.
TI Engineering a Novel Retroviral Envelope to Retarget Retroviral Vectors
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Xu, Wenqin; Blankenship, Tiffany; Eiden, Maribeth V.] NIH, Sect Directed Gene Transfer, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2014
VL 22
SU 1
MA 58
BP S23
EP S23
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300058
ER
PT J
AU Zhou, S
Tang, CL
Rapp, S
Bonner, MA
De Ravin, SS
Malech, HL
Sorrentino, BP
AF Zhou, Sheng
Tang, Chunlao
Rapp, Samuel
Bonner, Melissa A.
De Ravin, Suk See
Malech, Harry L.
Sorrentino, Brian P.
TI A Novel Non-Restrictive, Semi-Quantitative Method for Vector Insertion
Site Analysis Based on Random Shearing of Genomic DNA
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 17th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 21-24, 2014
CL Washington, DC
SP Amer Soc Gene & Cell Therapy, Genzyme
C1 [Zhou, Sheng; Tang, Chunlao; Rapp, Samuel; Bonner, Melissa A.; Sorrentino, Brian P.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[De Ravin, Suk See; Malech, Harry L.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
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 MAY
PY 2014
VL 22
SU 1
MA 542
BP S211
EP S211
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AI9ED
UT WOS:000337231300537
ER
PT J
AU Mann, ZF
Thiede, BR
Chang, W
Shin, JB
May-Simera, HL
Lovett, M
Corwin, JT
Kelley, MW
AF Mann, Zoe F.
Thiede, Benjamin R.
Chang, Weise
Shin, Jung-Bum
May-Simera, Helen L.
Lovett, Michael
Corwin, Jeffrey T.
Kelley, Matthew W.
TI A gradient of Bmp7 specifies the tonotopic axis in the developing inner
ear
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ACTIVATED POTASSIUM CHANNELS; HAIR CELL REGENERATION; SUPPORTING CELLS;
ACTIN-FILAMENTS; BASILAR PAPILLA; LATERAL INHIBITION; BIRD COCHLEA;
EXPRESSION; STEREOCILIA; CHICK
AB The auditory systems of animals that perceive sounds in air are organized to separate sound stimuli into their component frequencies. Individual tones then stimulate mechanosensory hair cells located at different positions on an elongated frequency (tonotopic) axis. During development, immature hair cells located along the axis must determine their tonotopic position in order to generate frequency-specific characteristics. Expression profiling along the developing tonotopic axis of the chick basilar papilla (BP) identified a gradient of Bmp7. Disruption of that gradient in vitro or in ovo induces changes in hair cell morphologies consistent with a loss of tonotopic organization and the formation of an organ with uniform frequency characteristics. Further, the effects of Bmp7 in determination of positional identity are shown to be mediated through activation of the Mapk, Tak1. These results indicate that graded, Bmp7-dependent, activation of Tak1 signalling controls the determination of frequency-specific hair cell characteristics along the tonotopic axis.
C1 [Mann, Zoe F.; Chang, Weise; May-Simera, Helen L.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA.
[Thiede, Benjamin R.; Shin, Jung-Bum; Corwin, Jeffrey T.] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA.
[Lovett, Michael] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England.
RP Mann, ZF (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, 35A Convent Dr, Bethesda, MD 20892 USA.
EM mannz@nidcd.nih.gov; kelleymt@nidcd.nih.gov
FU Intramural Research Program at NIDCD [1RC1DC010677]; American Hearing
Research Foundation [R01-DC000200]; NRSA [F31 DC012485]
FX We thank Tom Coate and Jonathan Bird for technical assistance and Mark
Warchol and Thomas Friedman for providing comments on an earlier version
of the manuscript. This project was supported by funds from the
Intramural Research Program at NIDCD to M.W.K., grant 1RC1DC010677
(NIDCD) to M.L., a grant from the American Hearing Research Foundation
to M.L., NIDCD NIH grant R01-DC000200 to J.T.C. and NRSA F31 DC012485 to
B.T.
NR 58
TC 13
Z9 13
U1 2
U2 7
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 MAY
PY 2014
VL 5
AR 3839
DI 10.1038/ncomms4839
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0VE
UT WOS:000337373500001
PM 24845721
ER
PT J
AU Thiede, BR
Mann, ZF
Chang, WS
Ku, YC
Son, YK
Lovett, M
Kelley, MW
Corwin, JT
AF Thiede, Benjamin R.
Mann, Zoe F.
Chang, Weise
Ku, Yuan-Chieh
Son, Yena K.
Lovett, Michael
Kelley, Matthew W.
Corwin, Jeffrey T.
TI Retinoic acid signalling regulates the development of tonotopically
patterned hair cells in the chicken cochlea
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DEVELOPING INNER-EAR; ACTIN CROSS-LINKER; BIRD COCHLEA; RNA-SEQ;
STEREOCILIA; EXPRESSION; FILAMENTS; ORGAN; ESPIN; CORTI
AB Precise frequency discrimination is a hallmark of auditory function in birds and mammals and is required for distinguishing similar sounding words, like 'bat,' 'cat' and 'hat.' In the cochlea, tuning and spectral separation result from longitudinal differences in basilar membrane stiffness and numerous individual gradations in sensory hair cell phenotypes, but it is unknown what patterns the phenotypes. Here we used RNA-seq to compare transcriptomes from proximal, middle and distal regions of the embryonic chicken cochlea, and found opposing longitudinal gradients of expression for retinoic acid (RA)-synthesizing and degrading enzymes. In vitro experiments showed that RA is necessary and sufficient to induce the development of distal-like hair cell phenotypes and promotes expression of the actin-crosslinking proteins, Espin and Fscn2. These and other findings highlight a role for RA signalling in patterning the development of a longitudinal gradient of frequency-tuned hair cell phenotypes in the cochlea.
C1 [Thiede, Benjamin R.; Son, Yena K.; Corwin, Jeffrey T.] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA.
[Mann, Zoe F.; Chang, Weise; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA.
[Ku, Yuan-Chieh; Lovett, Michael] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA.
[Corwin, Jeffrey T.] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA.
RP Corwin, JT (reprint author), Univ Virginia, Sch Med, Dept Neurosci, 409 Lane Rd, Charlottesville, VA 22908 USA.
EM jtc2k@virginia.edu
FU National Institutes of Health [RO1 DC000200, RC1 DC010677, F31
DC012485]; American Hearing Research Foundation
FX We thank James Pagana, Wendy Baker and Jung-Bum Shin for technical
advice. This work was supported by grants from the National Institutes
of Health RO1 DC000200 (J.T.C.), RC1 DC010677 (M.L.), F31 DC012485
(B.R.T.) and the American Hearing Research Foundation (M.L.).
NR 64
TC 9
Z9 9
U1 0
U2 9
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 MAY
PY 2014
VL 5
AR 3840
DI 10.1038/ncomms4840
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AJ0VE
UT WOS:000337373500002
PM 24845860
ER
PT J
AU Tan, F
Thiele, CJ
Li, ZJ
AF Tan, Fei
Thiele, Carol J.
Li, Zhijie
TI Collapsin response mediator proteins: Potential diagnostic and
prognostic biomarkers in cancers
SO ONCOLOGY LETTERS
LA English
DT Review
DE collapsin response mediator proteins; biomarker; tumor suppressor;
metastasis
ID TISSUE GROWTH-FACTOR; DEVELOPING RAT-BRAIN; CELL LUNG-CANCER;
UNC-33-LIKE PHOSPHOPROTEIN; AXON GUIDANCE; MOLECULAR CHARACTERIZATION;
NEURONAL DIFFERENTIATION; GLIOBLASTOMA-MULTIFORME;
CAENORHABDITIS-ELEGANS; NEURITE OUTGROWTH
AB The collapsin response mediator proteins (CRMPs) were originally identified as mediators of semaphorin 3A signaling and neuronal differentiation. The CRMP family consists of five homologous cytosolic proteins, CRMP1-5. Altered expression levels of CRMPs have been observed in several malignant tumors, including lung, breast, colorectal, prostate, pancreatic and neuroendocrine lung cancer. The aim of the current study was to review the recent progress achieved in understanding the association between the different levels of CRMP expression in tumors and their involvement in pathological functions, such as tumor metastasis, disease progression, subtype differentiation and clinical outcome, to address the potential value of CRMPs as biomarkers for the diagnosis and prognosis of cancer patients.
C1 [Tan, Fei] China Med Univ, Dept Neurol, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China.
[Thiele, Carol J.] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Li, Zhijie] China Med Univ, Med Res Ctr, Shengjing Hosp, Shenyang 110004, Liaoning, Peoples R China.
RP Li, ZJ (reprint author), China Med Univ, Med Res Ctr, Shengjing Hosp, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China.
EM lizhijie68@hotmail.com
FU National Natural Science Foundation of China [81272538]; Society
Development Foundation of Liaoning Province [201225016]
FX This study was supported by the National Natural Science Foundation of
China (no. 81272538) and the Society Development Foundation of Liaoning
Province (no. 201225016).
NR 63
TC 4
Z9 4
U1 0
U2 6
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1792-1074
EI 1792-1082
J9 ONCOL LETT
JI Oncol. Lett.
PD MAY
PY 2014
VL 7
IS 5
BP 1333
EP 1340
DI 10.3892/ol:2014.1909
PG 8
WC Oncology
SC Oncology
GA AJ3HV
UT WOS:000337558000002
ER
PT J
AU Charles, RC
Hilaire, IJ
Mayo-Smith, LM
Teng, JE
Jerome, JG
Franke, MF
Saha, A
Yu, YN
Kovac, P
Calderwood, SB
Ryan, ET
LaRocque, RC
Almazor, CP
Qadri, F
Ivers, LC
Harris, JB
AF Charles, Richelle C.
Hilaire, Isabelle J.
Mayo-Smith, Leslie M.
Teng, Jessica E.
Jerome, J. Gregory
Franke, Molly F.
Saha, Amit
Yu, Yanan
Kovac, Paul
Calderwood, Stephen B.
Ryan, Edward T.
LaRocque, Regina C.
Almazor, Charles P.
Qadri, Firdausi
Ivers, Louise C.
Harris, Jason B.
TI Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral
Cholera Vaccine, Shanchol, in Haiti
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID FIELD-TRIAL; BLOOD-GROUP; BANGLADESH; RESPONSES; ANTIBODY; CHILDREN;
INFECTION; EFFICACY; ANTIGEN; SPECIFICITY
AB Background: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae.
Methodology/Principal Findings: We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-17 years), and 47 younger children (1-5 years) in Haiti, where cholera was introduced in 2010. A >= 4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A >= 2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age-and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine.
Conclusions/Significance: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae.
C1 [Charles, Richelle C.; Mayo-Smith, Leslie M.; Yu, Yanan; Calderwood, Stephen B.; Ryan, Edward T.; LaRocque, Regina C.; Harris, Jason B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.; LaRocque, Regina C.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hilaire, Isabelle J.; Teng, Jessica E.; Jerome, J. Gregory; Franke, Molly F.; Almazor, Charles P.; Ivers, Louise C.] Partners Hlth, Boston, MA USA.
[Teng, Jessica E.; Ivers, Louise C.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
[Franke, Molly F.; Ivers, Louise C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA.
[Saha, Amit; Qadri, Firdausi] Icddr B, Dhaka, Bangladesh.
[Kovac, Paul] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM rccharles@mgh.harvard.edu; livers@pih.org; jbharris@mgh.harvard.edu
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases [R01 AI099243, AI077883, AI058935, AI106878, K08
AI089721]; Bill and Melinda Gates Foundation [OPP50419]; Massachusetts
General Hospital Physician Scientist Development Award from
Massachusetts General Hospital
FX This work was supported by grants from the National Institutes of
Health, including the National Institute of Allergy and Infectious
Diseases (R01 AI099243; JBH, LCI), (AI077883, AI058935, AI106878 ETR),
and the Career Development Award (K08 AI089721; RCC); the Bill and
Melinda Gates Foundation (OPP50419; FQ); and a Massachusetts General
Hospital Physician Scientist Development Award from Massachusetts
General Hospital (RCC). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 39
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U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2014
VL 8
IS 5
AR e2828
DI 10.1371/journal.pntd.0002828
PG 8
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AJ5OS
UT WOS:000337735100025
PM 24786645
ER
PT J
AU Kamuyu, G
Bottomley, C
Mageto, J
Lowe, B
Wilkins, PP
Noh, JC
Nutman, TB
Ngugi, AK
Odhiambo, R
Wagner, RG
Kakooza-Mwesige, A
Owusu-Agyei, S
Ae-Ngibise, K
Masanja, H
Osier, FHA
Odermatt, P
Newton, CR
AF Kamuyu, Gathoni
Bottomley, Christian
Mageto, James
Lowe, Brett
Wilkins, Patricia P.
Noh, John C.
Nutman, Thomas B.
Ngugi, Anthony K.
Odhiambo, Rachael
Wagner, Ryan G.
Kakooza-Mwesige, Angelina
Owusu-Agyei, Seth
Ae-Ngibise, Kenneth
Masanja, Honorati
Osier, Faith H. A.
Odermatt, Peter
Newton, Charles R.
CA Epidemiology Epilepsy Demographic
TI Exposure to Multiple Parasites Is Associated with the Prevalence of
Active Convulsive Epilepsy in Sub-Saharan Africa
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID TOXOPLASMA-GONDII; ONCHOCERCA-VOLVULUS; CRYPTOGENIC EPILEPSY; RURAL
TANZANIA; RISK-FACTORS; NEUROCYSTICERCOSIS; TOXOCARIASIS; CYSTICERCOSIS;
INFECTION; RESPONSES
AB Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa.
Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95% CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95% CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95% CI: 1.04-1.56, p=0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95% CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas.
Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.
C1 [Kamuyu, Gathoni; Mageto, James; Lowe, Brett; Ngugi, Anthony K.; Odhiambo, Rachael; Osier, Faith H. A.; Newton, Charles R.] KEMRI Wellcome Trust Res Programme, Ctr Geog Med Res Coast, Kilifi, Kenya.
[Kamuyu, Gathoni; Lowe, Brett; Ngugi, Anthony K.; Kakooza-Mwesige, Angelina; Newton, Charles R.] Studies Epidemiol Epilepsy Demog Surveillance Sys, Accra, Ghana.
[Bottomley, Christian] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Dept Infect Dis Epidemiol, London WC1, England.
[Bottomley, Christian] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, MRC Trop Epidemiol Grp, London WC1, England.
[Bottomley, Christian] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England.
[Mageto, James] Egerton Univ, Nakuru, Kenya.
[Lowe, Brett] Univ Oxford, Nuffield Dept Clin Med, Oxford, England.
[Wilkins, Patricia P.; Noh, John C.] Ctr Dis Control & Prevent CDC, Div Parasit Dis & Malaria, Atlanta, GA USA.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Ngugi, Anthony K.] Aga Khan Univ East Africa, Fac Hlth Sci, Res Support Unit, Nairobi, Kenya.
[Wagner, Ryan G.] Univ Witwatersrand, Fac Hlth Sci, Sch Publ Hlth, MRC Wits Rural Publ Hlth & Hlth Transit Res Unit, Johannesburg, South Africa.
[Wagner, Ryan G.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Kakooza-Mwesige, Angelina] Iganga Mayuge Hlth & Demog Surveillance Syst, Iganga, Uganda.
[Kakooza-Mwesige, Angelina] Makerere Univ, Coll Hlth Sci, Dept Paediat & Child Hlth, Kampala, Uganda.
[Owusu-Agyei, Seth; Ae-Ngibise, Kenneth] Kintampo Hlth Res Ctr, Kintampo, Ghana.
[Masanja, Honorati] Ifakara Hlth Inst, Ifakara, Tanzania.
[Odermatt, Peter] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Odermatt, Peter] Unvers Basel, Basel, Switzerland.
[Newton, Charles R.] UCL Inst Child Hlth, Neurosci Unit, London, England.
[Newton, Charles R.] London Sch Hyg & Trop Med, Clin Res Unit, London WC1, England.
[Newton, Charles R.] Univ Oxford, Dept Psychiat, Oxford, England.
RP Kamuyu, G (reprint author), KEMRI Wellcome Trust Res Programme, Ctr Geog Med Res Coast, Kilifi, Kenya.
EM GKamuyu@kemri-wellcome.org
RI Sander, Josemir/C-1576-2008; Odermatt, Peter/K-7727-2015;
OI Sander, Josemir/0000-0001-6041-9661; Odermatt,
Peter/0000-0002-0296-2508; Osier, Faith/0000-0001-7133-5375; Newton,
Charles/0000-0002-6999-5507
FU Wellcome Trust through a Wellcome Trust Senior Fellowship in Clinical
Tropical Medicine [083744]; Wellcome Trust through a strategic training
award [084538]; Wellcome Trust Master's Training Fellowship [096392]
FX The Wellcome Trust funded this research through a Wellcome Trust Senior
Fellowship in Clinical Tropical Medicine (No. 083744 to CRN), and
supported GK to write up this work through a strategic training award
(No. 084538) and a Wellcome Trust Master's Training Fellowship (No.
096392) to KEMRI-Wellcome Trust Research Programme. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 52
TC 20
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U1 0
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2014
VL 8
IS 5
AR e2908
DI 10.1371/journal.pntd.0002908
PG 10
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AJ5OS
UT WOS:000337735100075
PM 24875312
ER
PT J
AU Rivoire, BL
Groathouse, NA
TerLouw, S
Neupane, KD
Ranjit, C
Sapkota, BR
Khadge, S
Kunwar, CB
Macdonald, M
Hawksworth, R
Thapa, MB
Hagge, DA
Tibbals, M
Smith, C
Dube, T
She, DW
Wolff, M
Zhou, E
Makhene, M
Mason, R
Sizemore, C
Brennan, PJ
AF Rivoire, Becky L.
Groathouse, Nathan A.
TerLouw, Stephen
Neupane, Kapil Dev
Ranjit, Chaman
Sapkota, Bishwa Raj
Khadge, Saraswoti
Kunwar, Chatra B.
Macdonald, Murdo
Hawksworth, Rachel
Thapa, Min B.
Hagge, Deanna A.
Tibbals, Melinda
Smith, Carol
Dube, Tina
She, Dewei
Wolff, Mark
Zhou, Eric
Makhene, Mamodikoe
Mason, Robin
Sizemore, Christine
Brennan, Patrick J.
TI Safety and Efficacy Assessment of Two New Leprosy Skin Test Antigens:
Randomized Double Blind Clinical Study
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID DELAYED-TYPE HYPERSENSITIVITY; LEPRAE SOLUBLE-ANTIGENS;
MYCOBACTERIUM-LEPRAE; ENVIRONMENTAL MYCOBACTERIA; ENDEMIC POPULATION;
TUBERCULOSIS; CONTACTS; LIPOARABINOMANNAN; DIAGNOSIS; TRIAL
AB Background: New tools are required for the diagnosis of pre-symptomatic leprosy towards further reduction of disease burden and its associated reactions. To address this need, two new skin test antigens were developed to assess safety and efficacy in human trials.
Methods: A Phase I safety trial was first conducted in a non-endemic region for leprosy (U. S. A.). Healthy non-exposed subjects (n = 10) received three titrated doses (2.5 mu g, 1.0 mu g and 0.1 mu g) of MLSA-LAM (n = 5) or MLCwA (n = 5) and control antigens [Rees MLSA (1.0 mu g) and saline]. A randomized double blind Phase II safety and efficacy trial followed in an endemic region for leprosy (Nepal), but involved only the 1.0 mg (high dose) and 0.1 mu g (low dose) of each antigen; Tuberculin PPD served as a control antigen. This Phase II safety and efficacy trial consisted of three Stages: Stage A and B studies were an expansion of Phase I involving 10 and 90 subjects respectively, and Stage C was then conducted in two parts (high dose and low dose), each enrolling 80 participants: 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients, 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients, 20 household contacts of leprosy patients (HC), and 20 tuberculosis (TB) patients. The primary outcome measure for the skin test was delayed type hypersensitivity induration.
Findings: In the small Phase I safety trial, reactions were primarily against the 2.5 mu g dose of both antigens and Rees control antigen, which were then excluded from subsequent studies. In the Phase II, Stage A/B ramped-up safety study, 26% of subjects (13 of 50) showed induration against the high dose of each antigen, and 4% (2 of 50) reacted to the low dose of MLSA-LAM. Phase II, Stage C safety and initial efficacy trial showed that both antigens at the low dose exhibited low sensitivity at 20% and 25% in BT/TT leprosy patients, but high specificity at 100% and 95% compared to TB patients. The high dose of both antigens showed lower specificity (70% and 60%) and sensitivity (10% and 15%). BL/LL leprosy patients were anergic to the leprosy antigens.
Interpretation: MLSA-LAM and MLCwA at both high (1.0 mu g) and low (0.1 mu g) doses were found to be safe for use in humans without known exposure to leprosy and in target populations. At a sensitivity rate of 20-25% these antigens are not suitable as a skin test for the detection of the early stages of leprosy infection; however, the degree of specificity is impressive given the presence of cross-reactive antigens in these complex native M. leprae preparations.
C1 [Rivoire, Becky L.; Groathouse, Nathan A.; TerLouw, Stephen; Brennan, Patrick J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Neupane, Kapil Dev; Ranjit, Chaman; Sapkota, Bishwa Raj; Khadge, Saraswoti; Kunwar, Chatra B.; Macdonald, Murdo; Hawksworth, Rachel; Thapa, Min B.; Hagge, Deanna A.] Anandaban Hosp, Mycobacterial Res Lab, Kathmandu, Nepal.
[Tibbals, Melinda; Smith, Carol; Dube, Tina; She, Dewei; Wolff, Mark] EMMES Corp, Rockville, MD USA.
[Zhou, Eric; Makhene, Mamodikoe; Mason, Robin; Sizemore, Christine] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Rivoire, BL (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
EM brivoire@alumni.colostate.edu
RI Sapkota, Bishwa/B-6403-2012;
OI Hagge, Deanna A./0000-0002-3792-2266
FU NIH, NIAID [NO1 AI-25469, AI 082575]
FX This work was funded by NIH, NIAID NO1 AI-25469 and NIH, NIAID AI
082575; website address: http://www.niaid.nih.gov/. The funder provided
regulatory guidance, help with study design and management, and
subcontracted data handling and site monitoring, but played no role in
data analysis or preparation of the manuscript.
NR 52
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Z9 2
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2014
VL 8
IS 5
AR e2811
DI 10.1371/journal.pntd.0002811
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AJ5OS
UT WOS:000337735100018
PM 24874401
ER
PT J
AU VanWormer, E
Miller, MA
Conrad, PA
Grigg, ME
Rejmanek, D
Carpenter, TE
Mazet, JAK
AF VanWormer, Elizabeth
Miller, Melissa A.
Conrad, Patricia A.
Grigg, Michael E.
Rejmanek, Daniel
Carpenter, Tim E.
Mazet, Jonna A. K.
TI Using Molecular Epidemiology to Track Toxoplasma gondii from Terrestrial
Carnivores to Marine Hosts: Implications for Public Health and
Conservation
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID ENHYDRA-LUTRIS-NEREIS; SEA OTTERS; SOUTHERN CALIFORNIA; FRENCH-GUIANA;
POPULATION-GENETICS; DISEASE ECOLOGY; DRINKING-WATER; MOUNTAIN LIONS;
UNITED-STATES; OOCYSTS
AB Background: Environmental transmission of the zoonotic parasite Toxoplasma gondii, which is shed only by felids, poses risks to human and animal health in temperate and tropical ecosystems. Atypical T. gondii genotypes have been linked to severe disease in people and the threatened population of California sea otters. To investigate land-to-sea parasite transmission, we screened 373 carnivores (feral domestic cats, mountain lions, bobcats, foxes, and coyotes) for T. gondii infection and examined the distribution of genotypes in 85 infected animals sampled near the sea otter range.
Methodology/Principal Findings: Nested PCR-RFLP analyses and direct DNA sequencing at six independent polymorphic genetic loci (B1, SAG1, SAG3, GRA6, L358, and Apico) were used to characterize T. gondii strains in infected animals. Strains consistent with Type X, a novel genotype previously identified in over 70% of infected sea otters and four terrestrial wild carnivores along the California coast, were detected in all sampled species, including domestic cats. However, odds of Type X infection were 14 times higher (95% CI: 1.3-148.6) for wild felids than feral domestic cats. Type X infection was also linked to undeveloped lands (OR = 22, 95% CI: 2.3-250.7). A spatial cluster of terrestrial Type II infection (P = 0.04) was identified in developed lands bordering an area of increased risk for sea otter Type II infection. Two spatial clusters of animals infected with strains consistent with Type X (P <= 0.01) were detected in less developed landscapes.
Conclusions: Differences in T. gondii genotype prevalence among domestic and wild felids, as well as the spatial distribution of genotypes, suggest co-existing domestic and wild T. gondii transmission cycles that likely overlap at the interface of developed and undeveloped lands. Anthropogenic development driving contact between these cycles may increase atypical T. gondii genotypes in domestic cats and facilitate transmission of potentially more pathogenic genotypes to humans, domestic animals, and wildlife.
C1 [VanWormer, Elizabeth; Miller, Melissa A.; Conrad, Patricia A.; Rejmanek, Daniel; Mazet, Jonna A. K.] Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Wildlife Hlth Ctr, Davis, CA 95616 USA.
[Miller, Melissa A.] Calif Dept Fish & Wildlife, Marine Wildlife Vet Care & Res Ctr, Santa Cruz, CA USA.
[Conrad, Patricia A.; Rejmanek, Daniel] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Carpenter, Tim E.] Massey Univ, EpiCtr, Palmerston North, New Zealand.
RP VanWormer, E (reprint author), Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Wildlife Hlth Ctr, Davis, CA 95616 USA.
EM evanwormer@ucdavis.edu
FU National Science Foundation Ecology of Infectious Disease Program
[0525765, 1065990]; NIH; NIAID; UC Davis Wildlife Health Center
FX Grants from the National Science Foundation Ecology of Infectious
Disease Program (0525765, 1065990), the Intramural Research Program of
the NIH and NIAID (MEG), and the UC Davis Wildlife Health Center
supported this research. MEG is a scholar of the CIFAR Integrated
Microbial Biodiversity Program. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 77
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U1 2
U2 65
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD MAY
PY 2014
VL 8
IS 5
AR e2852
DI 10.1371/journal.pntd.0002852
PG 14
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA AJ5OS
UT WOS:000337735100046
PM 24874796
ER
PT J
AU Canna, SW
AF Canna, Scott W.
TI Interferon-gamma: Friend or Foe in Systemic Juvenile Idiopathic
Arthritis and Adult-Onset Still's Disease?
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Editorial Material
ID MACROPHAGE ACTIVATION SYNDROME; MICE; HEMOPHAGOCYTOSIS; SUBSETS; ANEMIA
C1 [Canna, Scott W.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Canna, SW (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM scott.canna@nih.gov
OI Canna, Scott/0000-0003-3837-5337
NR 17
TC 6
Z9 6
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAY
PY 2014
VL 66
IS 5
BP 1072
EP 1076
DI 10.1002/art.38362
PG 5
WC Rheumatology
SC Rheumatology
GA AJ0RM
UT WOS:000337363400003
PM 24470448
ER
PT J
AU Golding, A
Shavach, EM
Hasni, S
Illei, G
AF Golding, Amit
Shavach, Ethan M.
Hasni, Sarfaraz
Illei, Gabor
TI FoxP3+Helios- Treg cells may play a critical role in maintaining immune
homeostasis in systemic lupus erythematosus: comment on the article by
Golding et al Reply
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Letter
C1 [Golding, Amit; Shavach, Ethan M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Hasni, Sarfaraz] Natl Inst Musculoskeletal & Skin Dis, NIH, Bethesda, MD USA.
[Illei, Gabor] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Golding, A (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 3
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD MAY
PY 2014
VL 66
IS 5
BP 1403
EP 1404
DI 10.1002/art.38377
PG 3
WC Rheumatology
SC Rheumatology
GA AJ0RM
UT WOS:000337363400046
PM 24470345
ER
PT J
AU Gilman, JK
Wright, M
Lane, HC
Schoomaker, EB
AF Gilman, James K.
Wright, Mary
Lane, H. Clifford
Schoomaker, Eric B.
TI A MODEL OF FEDERAL INTERAGENCY COOPERATION: THE NATIONAL INTERAGENCY
CONFEDERATION FOR BIOLOGICAL RESEARCH
SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE
LA English
DT Article
AB The terrorist attacks of September 11 and the anthrax mailings a month later prompted a sweeping response by the federal government to improve the preparedness of the US to meet the potential threat posed by a terrorist using a biological agent. This response transcended traditional interagency boundaries, creating new opportunities while producing unique fiscal and leadership challenges. The National Interagency Confederation for Biological Research has made significant progress over the past 12 years because of its ability to adapt to the need for interagency cooperation and overcome many of these challenges. As construction of the National Interagency Biodefense Campus at Fort Detrick nears completion, the US has the capability to pursue a unique whole-of-government approach to the development of medical measures to counter the threat of bioterrorism. In addition to the high-level support of many in the federal government, the key success factors for this effort have been (1) a critical mass of leaders with the right leadership characteristics, (2) development of a compelling vision and accompanying narrative understood and articulated by all partnering organizations, and (3) recognition of the need for a partnership office to do the important communication and collaboration work in the organization to synchronize the information available to all the partners. The major barrier to interagency cooperative efforts of this kind is the inability to comingle funds from different appropriations.
C1 [Gilman, James K.] Johns Hopkins Mil & Vet Hlth Inst, Glen Burnie, MD 21060 USA.
[Wright, Mary; Lane, H. Clifford] NIAID, Div Clin Res, Bethesda, MD 20892 USA.
[Schoomaker, Eric B.] Uniform Serv Univ Hlth Sci, Bethesda, MD USA.
RP Gilman, JK (reprint author), Johns Hopkins Mil & Vet Hlth Inst, 6704 Curtis Court, Glen Burnie, MD 21060 USA.
EM jgilman5@jhu.edu
NR 2
TC 2
Z9 2
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1538-7135
EI 1557-850X
J9 BIOSECUR BIOTERROR
JI Biosecur. Bioterror.
PD MAY-JUN
PY 2014
VL 12
IS 3
BP 144
EP 150
DI 10.1089/bsp.2013.0084
PG 7
WC Public, Environmental & Occupational Health; International Relations
SC Public, Environmental & Occupational Health; International Relations
GA AI9BP
UT WOS:000337221900004
PM 24819736
ER
PT J
AU Kosakowska-Cholody, T
Lin, J
Srideshikan, SM
Scheffer, L
Tarasova, NI
Acharya, JK
AF Kosakowska-Cholody, T.
Lin, J.
Srideshikan, S. M.
Scheffer, L.
Tarasova, N. I.
Acharya, J. K.
TI HKH40A downregulates GRP78/BiP expression in cancer cells
SO CELL DEATH & DISEASE
LA English
DT Article
DE HKH40A; GRP78/BiP; unfolded Protein Response (UPR); chemoresistance;
cancer; paraptosis
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; HUMAN
LUNG-CANCER; MICROSCALE THERMOPHORESIS; CLINICAL-SIGNIFICANCE;
GROWTH-INHIBITION; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER;
UP-REGULATION; APOPTOSIS
AB HKH40A, the 8-methoxy analog of WMC79, is a synthetic agent with promising in vitro and in vivo antitumor activity, especially against solid tumors. However, molecular mechanisms underlying its antitumor effects are poorly understood. Here, we report that HKH40A markedly reduces the level of GRP78/BiP protein in cancer cell lines of various origin. In this study, we show that HKH40A not only downregulates transcription of GRP78 but also directly binds to the isolated protein and induces its proteosomal degradation. Knockdown of BiP increased the efficacy of the drug and overexpression of BiP diminished its activity. BiP is generally highly elevated in solid tumors having a pivotal role in cancer cell survival and chemoresistance, and has been suggested as a novel target for therapeutic intervention. We show that reduction of BiP level by HKH40A impairs its function and induces unfolded protein response as evidenced by the activation of IRE1 alpha, ATF6 and PERK. This leads to a series of downstream events, including sustained eIF2 alpha phosphorylation, increased abundance of spliced XBP1 mRNA and protein levels of ATF4 and CHOP. We also demonstrate that HKH40A inhibited tumor formation in an in vivo xenograft tumor model. Collectively, our data show that HKH40A reduces BiP levels and this could have an important role in the activity of HKH40A against cancer cells.
C1 [Kosakowska-Cholody, T.; Lin, J.; Srideshikan, S. M.; Scheffer, L.; Acharya, J. K.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
[Tarasova, N. I.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Acharya, JK (reprint author), NCI, Lab Cell & Dev Signaling, Rm 22-90B,Bldg 560,1050 Boyles St, Frederick, MD 21702 USA.
EM acharyaj@mail.nih.gov
NR 49
TC 9
Z9 9
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAY
PY 2014
VL 5
SI SI
AR e1240
DI 10.1038/cddis.2014.203
PG 10
WC Cell Biology
SC Cell Biology
GA AI9DN
UT WOS:000337229300040
PM 24853418
ER
PT J
AU Lu, H
Fang, EF
Sykora, P
Kulikowicz, T
Zhang, Y
Becker, KG
Croteau, DL
Bohr, VA
AF Lu, H.
Fang, E. F.
Sykora, P.
Kulikowicz, T.
Zhang, Y.
Becker, K. G.
Croteau, D. L.
Bohr, V. A.
TI Senescence induced by RECQL4 dysfunction contributes to Rothmund-Thomson
syndrome features in mice
SO CELL DEATH & DISEASE
LA English
DT Article
DE RecQ helicase; RECQ4; RECQL4; senescence; Rothmund-Thomson syndrome;
premature aging
ID CELLULAR SENESCENCE; DNA-REPLICATION; WERNER-SYNDROME; GENOMIC
INSTABILITY; HELICASE DOMAIN; GENE-PRODUCT; IN-VIVO; PROTEIN;
FIBROBLASTS; STRESS
AB Cellular senescence refers to irreversible growth arrest of primary eukaryotic cells, a process thought to contribute to aging-related degeneration and disease. Deficiency of RecQ helicase RECQL4 leads to Rothmund-Thomson syndrome (RTS), and we have investigated whether senescence is involved using cellular approaches and a mouse model. We first systematically investigated whether depletion of RECQL4 and the other four human RecQ helicases, BLM, WRN, RECQL1 and RECQL5, impacts the proliferative potential of human primary fibroblasts. BLM-, WRN- and RECQL4-depleted cells display increased staining of senescence-associated beta-galactosidase (SA-beta-gal), higher expression of p16(INK4a) or/and p21(WAF1) and accumulated persistent DNA damage foci. These features were less frequent in RECQL1-and RECQL5-depleted cells. We have mapped the region in RECQL4 that prevents cellular senescence to its N-terminal region and helicase domain. We further investigated senescence features in an RTS mouse model, Recql4-deficient mice (Recql4(HD)). Tail fibroblasts from Recql4(HD) showed increased SA-beta-gal staining and increased DNA damage foci. We also identified sparser tail hair and fewer blood cells in Recql4(HD) mice accompanied with increased senescence in tail hair follicles and in bone marrow cells. In conclusion, dysfunction of RECQL4 increases DNA damage and triggers premature senescence in both human and mouse cells, which may contribute to symptoms in RTS patients.
C1 [Lu, H.; Fang, E. F.; Sykora, P.; Kulikowicz, T.; Croteau, D. L.; Bohr, V. A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Zhang, Y.; Becker, K. G.] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Room 06B133A,251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
FU Intramural Research Program of the NIH; NIA
FX Mice were rederived from a pair of mice from Dr. Guangbin Luo of Case
Western Reserve University. We thank Dr. Elin Lehrmann from the
Microarray faculty of NIA for her assistance in performing microarray.
We thank Vickie Hoffmann from NIH Division of Veterinary Resources for
the comprehensive gross and histopathologic analyses. We also thank
Jingyan Tian, Joseph Hsu and Lale Dawut for their technical support. We
also want to thank Drs. Beverly Baptiste, Raghavendra Shamanna, Mengxia
Li and Takashi Tadokoro at the NIA for their critical discussions. This
research was supported entirely by the Intramural Research Program of
the NIH, NIA.
NR 60
TC 9
Z9 9
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD MAY
PY 2014
VL 5
SI SI
AR e1226
DI 10.1038/cddis.2014.168
PG 12
WC Cell Biology
SC Cell Biology
GA AI9DN
UT WOS:000337229300026
PM 24832598
ER
PT J
AU Ostroumova, E
Gudzenko, N
Brenner, A
Gorokh, Y
Hatch, M
Prysyazhnyuk, A
Mabuchi, K
Bazyka, D
AF Ostroumova, Evgenia
Gudzenko, Nataliya
Brenner, Alina
Gorokh, Yevgeniy
Hatch, Maureen
Prysyazhnyuk, Anatoliy
Mabuchi, Kiyohiko
Bazyka, Dimitry
TI Thyroid cancer incidence in Chornobyl liquidators in Ukraine: SIR
analysis, 1986-2010
SO EUROPEAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Thyroid cancer; Liquidators; Clean-up workers; Chornobyl; Chernobyl;
Ukraine
ID CLEANUP WORKERS; RISK; EXPOSURE; RADIATION; COHORT; ACCIDENT; REGISTRY
AB We studied thyroid cancer incidence in a cohort of 150,813 male Chornobyl clean-up workers ("liquidators") from Ukraine by calculating standardized incidence ratio (SIR) using national cancer statistics. Follow-up began on the liquidator's registration date with the Chornobyl State Registry of Ukraine (the earliest date was 05. 05. 1986) and continued through December 31, 2010, date of thyroid cancer diagnosis, date of death, or date of last known vital status, whichever came first. There were 196 incident thyroid cancers in the study cohort with an overall SIR of 3.50 [95 % confidence interval (CI) 3.04-4.03]. A significantly elevated SIR estimate of 3.86 (95 % CI 3.26-4.57) was observed for liquidators who had their first clean-up mission in the Chornobyl zone in 1986, when levels of external and internal exposure to radiation were highest; the SIR estimates for later calendar years of first clean-up mission, while significantly elevated, were lower. The SIR estimates were elevated throughout the entire follow-up period but were especially high 10-18 years after the accident: 4.62 (95 % CI 3.47-6.15) and 4.80 (95 % CI 3.78-6.10) for the period 1995-1999 and 2000-2004, respectively. Our findings support the growing evidence of increased thyroid cancer rates among Chornobyl liquidators. Although this could be partially attributed to increased medical surveillance, the observed pattern of SIR increase warrants further investigation of a potential contribution of radiation exposure to the elevated thyroid cancer rates in this large population.
C1 [Ostroumova, Evgenia; Brenner, Alina; Hatch, Maureen; Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Gudzenko, Nataliya; Prysyazhnyuk, Anatoliy; Bazyka, Dimitry] Natl Res Ctr Radiat Med, Kiev, Ukraine.
[Gorokh, Yevgeniy] Natl Canc Inst, Kiev, Ukraine.
RP Ostroumova, E (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM eostroumova@gmail.com
OI Bazyka, Dimitry/0000-0001-9982-5990
FU Intramural Research Program of the NIH, National Cancer Institute (USA)
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute (USA). We acknowledge the contribution of
Zoya Fedorenko (Ukrainian National Cancer Register, Ukraine), Nataliya
Babkina and Nataliya Trotsiuk (National Research Center for Radiation
Medicine, Ukraine) to the study execution. We thank Anatoliy Romanenko,
Vadim Chumak, Yuriy Belyayev (National Research Center for Radiation
Medicine, Ukraine) and Vladimir Drozdovitch (National Cancer Institute,
USA) for helpful discussions of study results.
NR 21
TC 1
Z9 1
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0393-2990
EI 1573-7284
J9 EUR J EPIDEMIOL
JI Eur. J. Epidemiol.
PD MAY
PY 2014
VL 29
IS 5
BP 337
EP 342
DI 10.1007/s10654-014-9896-1
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI8GI
UT WOS:000337148200004
PM 24705729
ER
PT J
AU Mukhopadhyay, P
Rajesh, M
Cao, ZX
Horvath, B
Park, O
Wang, H
Erdelyi, K
Holovac, E
Wang, YP
Liaudet, L
Hamdaoui, N
Lafdil, F
Hasko, G
Szabo, C
Boulares, AH
Gao, B
Pacher, P
AF Mukhopadhyay, Partha
Rajesh, Mohanraj
Cao, Zongxian
Horvath, Bela
Park, Ogyi
Wang, Hua
Erdelyi, Katalin
Holovac, Eileen
Wang, Yuping
Liaudet, Lucas
Hamdaoui, Nabila
Lafdil, Fouad
Hasko, Gyoergy
Szabo, Csaba
Boulares, A. Hamid
Gao, Bin
Pacher, Pal
TI Poly (ADP-Ribose) Polymerase-1 Is a Key Mediator of Liver Inflammation
and Fibrosis
SO HEPATOLOGY
LA English
DT Article
ID HEPATIC STELLATE CELLS; GROWTH-FACTOR; POLY(ADP-RIBOSE) POLYMERASE;
HEPATOCELLULAR-CARCINOMA; ADIPOCYTE FUNCTION; ACTIVATION; PATHWAY;
PHAGOCYTOSIS; RIBOSYLATION; FIBROGENESIS
AB Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we investigated the role of PARP-1 in liver inflammation and fibrosis using acute and chronic models of carbon tetrachloride (CCl4)-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo. Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4-induced hepatocyte death, inflammation, and fibrosis. Interestingly, the chronic CCl4-induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4-induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted. Conclusion: The reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism, and fibrosis. PARP inhibitors are currently in clinical trials for oncological indications, and the current results indicate that liver inflammation and liver fibrosis may be additional clinical indications where PARP inhibition may be of translational potential. (Hepatology 2014;59:1998-2009)
C1 [Mukhopadhyay, Partha; Rajesh, Mohanraj; Cao, Zongxian; Horvath, Bela; Erdelyi, Katalin; Holovac, Eileen; Wang, Yuping; Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20852 USA.
[Horvath, Bela] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA.
[Park, Ogyi; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20852 USA.
[Liaudet, Lucas] BH 08 621 Univ Hosp Med Ctr, Dept Intens Care Med, Lausanne, Switzerland.
[Hamdaoui, Nabila; Lafdil, Fouad] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France.
[Hamdaoui, Nabila; Lafdil, Fouad] Univ Paris Est, Fac Med, UMR S955, Creteil, France.
[Hasko, Gyoergy] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ USA.
[Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA.
[Boulares, A. Hamid] Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, New Orleans, LA USA.
[Boulares, A. Hamid] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol, New Orleans, LA USA.
RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20852 USA.
EM pacher@mail.nih.gov
RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; Liaudet,
Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU NIH/NIAAA; NIH [P50GM060338, HL072889]
FX Supported by the Intramural Program of the NIH/NIAAA to PP and BG. CS
and AHB were supported by a grant from the NIH P50GM060338 and HL072889.
NR 28
TC 26
Z9 27
U1 0
U2 11
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 MAY
PY 2014
VL 59
IS 5
BP 1998
EP +
DI 10.1002/hep.26763
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AI9TA
UT WOS:000337278400039
PM 24089324
ER
PT J
AU Niciu, MJ
Luckenbaugh, DA
Ionescu, DF
Guevara, S
Machado-Vieira, R
Richards, EM
Brutsche, NE
Nolan, NM
Zarate, CA
AF Niciu, Mark J.
Luckenbaugh, David A.
Ionescu, Dawn F.
Guevara, Sara
Machado-Vieira, Rodrigo
Richards, Erica M.
Brutsche, Nancy E.
Nolan, Neal M.
Zarate, Carlos A., Jr.
TI Clinical Predictors of Ketamine Response in Treatment-Resistant Major
Depression
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID RAPID ANTIDEPRESSANT RESPONSE; D-ASPARTATE ANTAGONIST; ADD-ON TRIAL;
BIPOLAR DEPRESSION; ALCOHOL DEPENDENCE; MOOD DISORDERS; GLUTAMATERGIC
NEUROTRANSMISSION; NMDA ANTAGONIST; FAMILY-HISTORY; EFFICACY
AB Objective: The N-methyl-d-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically heterogeneous populations.
Method: Data were analyzed from 4 studies of treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I or II depression. Patients who were currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5 mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute postinfusion time point (n = 108), at day 1 (n = 82), and at day 7 (n = 71). Univariate Pearson correlations were performed for each variable with percent change from baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (P =.05, 2-tailed).
Results: Higher body mass index correlated with greater HDRS improvement at 230 minutes (standardized beta = -0.30, P =.004) and at day 1 (standardized beta = -0.37, P =.001), but not at day 7 (standardized beta = -0.18, P =.10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at day 1 (standardized beta = -0.27, P =.014) and day 7 (standardized beta = -0.41, P <.001). No prior history of suicide attempt(s) was associated with greater improvement only at day 7 (standardized beta = 0.28, P =.01). The overall statistical model explained 13%, 23%, and 36% of HDRS percent change variance at 230 minutes, day 1, and day 7, respectively.
Conclusions: Despite its post hoc nature, this study identified several clinical correlates of ketamine's rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression. (C) Copyright 2014 Physicians Postgraduate Press, Inc.
C1 [Niciu, Mark J.; Luckenbaugh, David A.; Ionescu, Dawn F.; Guevara, Sara; Machado-Vieira, Rodrigo; Richards, Erica M.; Brutsche, Nancy E.; Nolan, Neal M.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, IRP, NIH, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), Bldg 10 Clin Res Ctr CRC,10 Ctr Dr,Room 7-5342, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012; Niciu, Mark/J-1766-2014; Ionescu,
Dawn/K-5675-2015
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Niciu,
Mark/0000-0002-5612-3021;
FU IRP-NIMH-NIH; NARSAD; Brain and Behavior Research Foundation
FX Funding for this work was supported by the IRP-NIMH-NIH, by a NARSAD
Independent Investigator Award to Dr Zarate, and by the Brain and
Behavior Mood Disorders Research Award from the Brain and Behavior
Research Foundation (formerly NARSAD) to Dr Zarate.
NR 38
TC 25
Z9 26
U1 3
U2 12
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAY
PY 2014
VL 75
IS 5
BP E417
EP E423
DI 10.4088/JCP.13m08698
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA AI9LZ
UT WOS:000337255400003
PM 24922494
ER
PT J
AU Tooley, PW
Browning, M
Leighty, RM
AF Tooley, Paul W.
Browning, Marsha
Leighty, Robert M.
TI The effect of temperature on germination of chlamydospores of
Phytophthora ramorum
SO MYCOLOGIA
LA English
DT Article
DE overwintering; ramorum blight; resting spore; sudden oak death
ID SUDDEN OAK DEATH; PATHOGEN; SOIL; MANAGEMENT; CALIFORNIA; CINNAMOMI;
PALMIVORA; MEDIA
AB Mycelium-free chlamydospores of 12 isolates of P. ramorum representing three clonal lineages were produced with a method involving incubation in nonsterile sand at 20 C in darkness for 30 d. Chlamydospores were incubated on selective agar medium at 5, 10, 15, 20, 25 and 30 C and germination assessed after 1, 2, 4, 6 and 8 d incubation. The optimal temperature for germination based on 8 d incubation was 20 C for all three clonal lineages tested (NA1 NA2, EU1). Mean germination rates were 2, 21, 44, 67, 32 and 0 percent at 5, 10, 15, 20, 25 and 30 C respectively for all isolates combined. The highest mean germination rate was scored by isolates of the EU1 clonal lineage at 20 C (85%) after 8 d incubation However, substantial variation was observed among isolates within each clonal lineage. Overall temperatures and days of incubation on which germination was assessed isolates of the NA1 clonal lineage had the lowest mean germination, even though one isolate had the highest germination of any isolate in any lineage. The results indicate that 20 C is the optimal germination temperature for P. ramorum chlamydospores and that a great disparity in germination percentage can exist within isolates, even within a single clonal lineage.
C1 [Tooley, Paul W.; Browning, Marsha] USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD 21702 USA.
[Leighty, Robert M.] Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Tooley, PW (reprint author), USDA ARS, Foreign Dis Weed Sci Res Unit, 1301 Ditto Ave, Ft Detrick, MD 21702 USA.
EM paul.tooley@ars.usda.gov
NR 30
TC 3
Z9 3
U1 0
U2 13
PU ALLEN PRESS INC
PI LAWRENCE
PA 810 E 10TH ST, LAWRENCE, KS 66044 USA
SN 0027-5514
EI 1557-2536
J9 MYCOLOGIA
JI Mycologia
PD MAY-JUN
PY 2014
VL 106
IS 3
BP 424
EP 430
DI 10.3852/13-313
PG 7
WC Mycology
SC Mycology
GA AI7LF
UT WOS:000337071400006
PM 24871605
ER
PT J
AU Thiebaut, R
Drylewicz, J
Prague, M
Lacabaratz, C
Beq, S
Jarne, A
Croughs, T
Sekaly, RP
Lederman, MM
Sereti, I
Commenges, D
Levy, Y
AF Thiebaut, Rodolphe
Drylewicz, Julia
Prague, Melanie
Lacabaratz, Christine
Beq, Stephanie
Jarne, Ana
Croughs, Therese
Sekaly, Rafick-Pierre
Lederman, Michael M.
Sereti, Irini
Commenges, Daniel
Levy, Yves
TI Quantifying and Predicting the Effect of Exogenous Interleukin-7 on
CD4(+)T Cells in HIV-1 Infection
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID RECEIVING ANTIRETROVIRAL THERAPY; NAIVE T-CELLS; IN-VIVO; HOMEOSTATIC
PROLIFERATION; IMMUNE RECONSTITUTION; RHESUS MACAQUES; MEMORY CELLS;
IL-7; SURVIVAL; LYMPHOCYTES
AB Exogenous Interleukin-7 (IL-7), in supplement to antiretroviral therapy, leads to a substantial increase of all CD4(+) T cell subsets in HIV-1 infected patients. However, the quantitative contribution of the several potential mechanisms of action of IL-7 is unknown. We have performed a mathematical analysis of repeated measurements of total and naive CD4(+) T cells and their Ki67 expression from HIV-1 infected patients involved in three phase I/II studies (N = 53 patients). We show that, besides a transient increase of peripheral proliferation, IL-7 exerts additional effects that play a significant role in CD4(+) T cell dynamics up to 52 weeks. A decrease of the loss rate of the total CD4(+) T cell is the most probable explanation. If this effect could be maintained during repeated administration of IL-7, our simulation study shows that such a strategy may allow maintaining CD4(+) T cell counts above 500 cells/mu L with 4 cycles or fewer over a period of two years. This in-depth analysis of clinical data revealed the potential for IL-7 to achieve sustained CD4(+) T cell restoration with limited IL-7 exposure in HIV-1 infected patients with immune failure despite antiretroviral therapy.
C1 [Thiebaut, Rodolphe; Prague, Melanie; Jarne, Ana; Commenges, Daniel] INSERM, ISPED, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France.
[Thiebaut, Rodolphe; Prague, Melanie; Jarne, Ana; Commenges, Daniel] Univ Bordeaux, ISPED, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France.
[Thiebaut, Rodolphe; Prague, Melanie; Jarne, Ana; Commenges, Daniel] INRIA, SISTM Team, Bordeaux, France.
[Drylewicz, Julia] Univ Med Ctr Utrecht, Lab Translat Immunol, Utrecht, Netherlands.
[Drylewicz, Julia] Univ Utrecht, Dept Biol, Utrecht, Netherlands.
[Lacabaratz, Christine; Levy, Yves] Hop Henri Mondor, INSERM, Unite U955, F-94010 Creteil, France.
[Lacabaratz, Christine] Univ Paris Est, Fac Med, UMR S955, Creteil, France.
[Beq, Stephanie; Croughs, Therese] CYTHERIS, Issy Les Moulineaux, France.
[Sekaly, Rafick-Pierre] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA.
[Lederman, Michael M.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Cleveland, OH 44106 USA.
[Sereti, Irini] NIAID, NIH, Bethesda, MD 20892 USA.
[Levy, Yves] AP HP, Grp Henri Mondor Albert Chenevier, Immunol Clin, Creteil, France.
RP Thiebaut, R (reprint author), INSERM, ISPED, Ctr INSERM U897 Epidemiol Biostat, Bordeaux, France.
EM rodolphe.thiebaut@isped.u-bordeaux2.fr
NR 61
TC 10
Z9 10
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD MAY
PY 2014
VL 10
IS 5
AR e1003630
DI 10.1371/journal.pcbi.1003630
PG 12
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA AI9VB
UT WOS:000337288000038
PM 24853554
ER
PT J
AU Pavone, ME
Hirshfeld-Cytron, J
Tingen, C
Thomas, C
Thomas, J
Lowe, MP
Schink, JC
Woodruff, TK
AF Pavone, Mary Ellen
Hirshfeld-Cytron, Jennifer
Tingen, Candace
Thomas, Cristina
Thomas, Jessina
Lowe, M. Patrick
Schink, Julian C.
Woodruff, Teresa K.
TI Human Ovarian Tissue Cortex Surrounding Benign and Malignant Lesions
SO REPRODUCTIVE SCIENCES
LA English
DT Article
DE follicle density; ovarian cancer; endometriosis; ovarian tissue
cryopreservation; ovarian tissue transplantation; fertility preservation
ID MONOZYGOTIC TWINS DISCORDANT; INITIAL FOLLICLE POOL; FERTILITY
PRESERVATION; CANCER-PATIENTS; BRCA1-DEFICIENT MICE; GROWING FOLLICLES;
BREAST-CANCER; GERM-CELLS; TRANSPLANTATION; GROWTH
AB Objective: To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts. Materials and Methods: Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer. In all, 10 women were either pregnant or immediately postpartum. Results: Patients undergoing risk-reducing surgery had significantly decreased follicle count compared to physiologic control. Patients with cancer had significantly decreased counts compared to all other groups. There were no differences within the benign cohort. Conclusions: When compared to benign masses, the cortex surrounding an ovarian malignancy has decreased follicle density. The stretch impact may minimize any impact on total follicle numbers. Furthermore, there may be a proliferation of ovarian stroma, with the same number of follicles spread over a larger surface area. This information is important when counseling women with ovarian masses regarding the use of ovarian tissue cryopreservation.
C1 [Pavone, Mary Ellen] Northwestern Univ, Dept Obstet & Gynecol, Div Reprod Biol, Chicago, IL 60611 USA.
[Pavone, Mary Ellen] Northwestern Univ, Feinberg Sch Med, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA.
[Tingen, Candace] Univ Illinois, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Chicago, IL 60612 USA.
[Tingen, Candace] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
[Thomas, Cristina; Thomas, Jessina] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lowe, M. Patrick] Advocate Hlth Care, Gynecol Oncol, Chicago, IL USA.
[Schink, Julian C.] Northwestern Univ, Feinberg Sch Med, Div Gynecol Oncol, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
[Woodruff, Teresa K.] Northwestern Univ, Feinberg Sch Med, Div Fertil Preservat, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
RP Pavone, ME (reprint author), Northwestern Univ, Feinberg Sch Med, Div Reprod Endocrinol & Infertil, Chicago, IL 60611 USA.
EM mpavone@nmff.org
FU ASRM career development award; [K12HD050121]; [U54 HD076188]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship and/or publication of this article: Supported
by K12HD050121, ASRM career development award (to MEP), and U54 HD076188
(to TKW).
NR 59
TC 2
Z9 2
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1933-7191
EI 1933-7205
J9 REPROD SCI
JI Reprod. Sci.
PD MAY
PY 2014
VL 21
IS 5
BP 582
EP 589
DI 10.1177/1933719113506498
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AI9UM
UT WOS:000337285300005
PM 24096576
ER
PT J
AU Messer, RJ
Lavender, KJ
Hasenkrug, KJ
AF Messer, Ronald J.
Lavender, Kerry J.
Hasenkrug, Kim J.
TI Mice of the resistant H-2(b) haplotype mount broad CD4(+) T cell
responses against 9 distinct Friend virus epitopes
SO VIROLOGY
LA English
DT Article
DE Friend virus; CD4(+) T cells
ID MURINE LEUKEMIA-VIRUS; FBL-3 TUMOR-CELLS; RETROVIRUS INFECTION; ANTIGEN;
IMMUNITY; MODEL; GENE; IDENTIFICATION; MECHANISMS; EXPRESSION
AB To date, only a single Friend virus (FV) peptide recognized by CD4(+) T cells in FV-infected mice of the resistant H-2(b) haplotype has been described. To more thoroughly examine the repertoire of CD4(+) T cell responses in H-2(b) mice infected with this retrovirus, 18mer peptides spanning the FV gag, pol, and env coding regions with 11mer overlaps were synthesized. The peptides were then used to stimulate whole splenocytes and purified CD4(+) T cells from FV-infected mice in an IFN gamma ELISPOT assay. Nine new CD4(+) T cell epitopes were identified, 3 encoded by gag, 1 by pol, and 5 by env. The high resistance of H-2(b) mice could be related to this very broad CD4(+) T cell response against multiple peptides during FV infection. Published by Elsevier Inc.
C1 [Messer, Ronald J.; Lavender, Kerry J.; Hasenkrug, Kim J.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM khasenkrug@nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases and National Institutes of Health, USA
FX This work was funded by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases and National
Institutes of Health, USA.
NR 32
TC 5
Z9 5
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAY
PY 2014
VL 456
BP 139
EP 144
DI 10.1016/j.virol.2014.03.012
PG 6
WC Virology
SC Virology
GA AI9NF
UT WOS:000337258600014
PM 24889233
ER
PT J
AU Teterina, NL
Liu, GP
Maximova, OA
Pletnev, AG
AF Teterina, Natalya L.
Liu, Guangping
Maximova, Olga A.
Pletnev, Alexander G.
TI Silencing of neurotropic flavivirus replication in the central nervous
system by combining multiple microRNA target insertions in two distinct
viral genome regions
SO VIROLOGY
LA English
DT Article
DE Flavivirus; Micrornas; Neuropathogenesis
ID ATTENUATED VIRUS-VACCINES; INFLUENZA-A VIRUS; IMMUNE-RESPONSES; VECTOR
TROPISM; ENCEPHALITIS; RNA; RECOGNITION; MICE; NEUROINVASIVENESS;
NEUROVIRULENCE
AB In recent years, microRNA-targeting has become an effective strategy for selective control of tissue-tropism and pathogenesis of both DNA and RNA viruses. Here, using a neurotropic flavivirus as a model, we demonstrate that simultaneous miRNA targeting of the viral genome in the open reading frame and 3'-noncoding regions for brain-expressed miRNAs had an additive effect and produced a more potent attenuation of the virus compared to separate targeting of those regions. Multiple miRNA co-targeting of these two distantly located regions completely abolished the virus neurotropism as no viral replication was detected in the developing brain of neonatal mice. Furthermore, no viral antigens were detected in neurons, and neuronal integrity in the brain of mice was well preserved. This miRNA co-targeting approach can be adapted for other viruses in order to minimize their replication in a cell- or tissue-type specific manner, but most importantly, to prevent virus escape from miRNA-mediated silencing. Published by Elsevier Inc.
C1 [Teterina, Natalya L.; Liu, Guangping; Maximova, Olga A.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Pletnev, AG (reprint author), NIAID, NIH, Bldg 33,Room 3W10A,33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM apletnev@niaid.nih.gov
FU Division of Intramural Research Program of the National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 46
TC 8
Z9 9
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAY
PY 2014
VL 456
BP 247
EP 258
DI 10.1016/j.virol.2014.04.001
PG 12
WC Virology
SC Virology
GA AI9NF
UT WOS:000337258600025
PM 24889244
ER
PT J
AU Laughlin, MR
Bantle, JP
Havel, PJ
Parks, E
Klurfeld, DM
Teff, K
Maruvada, P
AF Laughlin, Maren R.
Bantle, John P.
Havel, Peter J.
Parks, Elizabeth
Klurfeld, David M.
Teff, Karen
Maruvada, Padma
TI Clinical Research Strategies for Fructose Metabolism
SO ADVANCES IN NUTRITION
LA English
DT Review
ID GLUCOSE-SWEETENED BEVERAGES; DE-NOVO LIPOGENESIS; MONOCYTE
CHEMOATTRACTANT PROTEIN-1; PLASMINOGEN-ACTIVATOR INHIBITOR-1;
LOW-DENSITY LIPOPROTEINS; FATTY-ACID SYNTHESIS; DIETARY FRUCTOSE; CORN
SYRUP; URIC-ACID; HIGH-CARBOHYDRATE
AB Fructose and simple sugars are a substantial part of the western diet, and their influence on human health remains controversial. Clinical studies in fructose nutrition have proven very difficult to conduct and interpret. NIH and USDA sponsored a workshop on 13-14 November 2012, "Research Strategies for Fructose Metabolism," to identify important scientific questions and parameters to be considered while designing clinical studies. Research is needed to ascertain whether there is an obesogenic role for fructose-containing sugars via effects on eating behavior and energy balance and whether there is a dose threshold beyond which these sugars promote progression toward diabetes and liver and cardiovascular disease, especially in susceptible populations. Studies tend to fall into 2 categories, and design criteria for each are described. Mechanistic studies are meant to validate observations made in animals or to elucidate the pathways of fructose metabolism in humans. These highly controlled studies often compare the pure monosaccharides glucose and fructose. Other studies are focused on clinically significant disease outcomes or health behaviors attributable to amounts of fructose-containing sugars typically found in the American diet. These are designed to test hypotheses generated from short-term mechanistic or epidemiologic studies and provide data for health policy. Discussion brought out the opinion that, although many mechanistic questions concerning the metabolism of monosaccharide sugars in humans remain to be addressed experimentally in small highly controlled studies, health outcomes research meant to inform health policy should use large, long-term studies using combinations of sugars found in the typical American diet rather than pure fructose or glucose.
C1 [Laughlin, Maren R.; Teff, Karen; Maruvada, Padma] NIDDK, NIH, Bethesda, MD 20892 USA.
[Bantle, John P.] Univ Minnesota, Dept Med, Div Endocrinol & Diabet, Minneapolis, MN 55455 USA.
[Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Nutr, Dept Mol Biosci, Davis, CA 95616 USA.
[Parks, Elizabeth] Univ Missouri, Inst Clin Translat Sci, Dept Nutr & Exercise Physiol, Columbia, MO USA.
[Klurfeld, David M.] USDA ARS, Beltsville, MD USA.
RP Laughlin, MR (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
OI Parks, Elizabeth/0000-0001-5681-1097
FU National Institutes of Health; USDA; National Institute of Diabetes and
Digestive and Kidney Diseases; National Heart Lung and Blood Institute;
Merck
FX On behalf of the organizers and participants in a 2012 National
Institutes of Health and USDA-sponsored workshop, 'clinical Research
Strategies for Fructose Metabolism." Funding for the workshop was from
the National Institute of Diabetes and Digestive and Kidney Diseases,
the National Heart Lung and Blood Institute, and the USDA.; Author
disclosures. E. Parks serves on the Atkins Nutritionals Scientific
Advisory Board, Merck Speakers Bureau and receives funding from Merck.
M. R. Laughlin, J. P Bantle, P. J. Havel, D. M. Klurfeld, K Taft, P.
Maruvada, no conflicts of interest
NR 76
TC 9
Z9 9
U1 3
U2 29
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 2161-8313
EI 2156-5376
J9 ADV NUTR
JI Adv. Nutr.
PD MAY
PY 2014
VL 5
IS 3
BP 248
EP 259
DI 10.3945/an.113.005249
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AI5CV
UT WOS:000336883900004
PM 24829471
ER
PT J
AU Ash, JA
Rapp, PR
AF Ash, Jessica A.
Rapp, Peter R.
TI A quantitative neural network approach to understanding aging phenotypes
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Graph theory; Neural networks; Neurocognitive aging
ID INTRINSIC FUNCTIONAL CONNECTIVITY; TEST-RETEST RELIABILITY;
RESTING-STATE NETWORKS; GRAPH-THEORETICAL ANALYSIS; DEFAULT-MODE
NETWORK; AGE-RELATED-CHANGES; ALZHEIMERS-DISEASE; HUMAN BRAIN;
STRUCTURAL CONNECTIVITY; TOPOLOGICAL PATTERNS
AB Basic research on neurocognitive aging has traditionally adopted a reductionist approach in the search for the basis of cognitive preservation versus decline. However, increasing evidence suggests that a network level understanding of the brain can provide additional novel insight into the structural and functional organization from which complex behavior and dysfunction emerge. Using graph theory as a mathematical framework to characterize neural networks, recent data suggest that alterations in structural and functional networks may contribute to individual differences in cognitive phenotypes in advanced aging. This paper reviews literature that defines network changes in healthy and pathological aging phenotypes, while highlighting the substantial overlap in key features and patterns observed across aging phenotypes. Consistent with current efforts in this area, here we outline one analytic strategy that attempts to quantify graph theory metrics more precisely, with the goal of improving diagnostic sensitivity and predictive accuracy for differential trajectories in neurocognitive aging. Ultimately, such an approach may yield useful measures for gauging the efficacy of potential preventative interventions and disease modifying treatments early in the course of aging. Published by Elsevier B.V.
C1 [Ash, Jessica A.; Rapp, Peter R.] NIA, Lab Behav Neurosci, Neurocognit Aging Sect, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Ash, JA (reprint author), NIA, Lab Behav Neurosci, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jessica.ash@nih.gov
FU Intramural Research Program of the National Institute on Aging
FX We would like to thank Dr. Yihong Yang for his invaluable comments on
this manuscript. This is original work supported by the Intramural
Research Program of the National Institute on Aging.
NR 63
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
EI 1872-9649
J9 AGEING RES REV
JI Ageing Res. Rev.
PD MAY
PY 2014
VL 15
BP 44
EP 50
DI 10.1016/j.arr.2014.02.001
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA AI4ZR
UT WOS:000336875700005
PM 24548925
ER
PT J
AU Liu, J
Sirenko, S
Juhaszova, M
Sollott, SJ
Shukla, S
Yaniv, Y
Lakatta, EG
AF Liu, Jie
Sirenko, Syevda
Juhaszova, Magdalena
Sollott, Steven J.
Shukla, Shweta
Yaniv, Yael
Lakatta, Edward G.
TI Age-associated abnormalities of intrinsic automaticity of sinoatrial
nodal cells are linked to deficient cAMP-PKA-Ca2+ signaling
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE aging; Ca2+ transient; intrinsic heart rate; pacemaker function; PKA
signaling
ID CARDIAC-PACEMAKER CELLS; LOCAL CA2+ RELEASES; RAT VENTRICULAR MYOCYTES;
SPONTANEOUS BEATING RATE; SARCOPLASMIC-RETICULUM; HEART-RATE;
ATRIAL-FIBRILLATION; DYNAMIC EXERCISE; SEX-DIFFERENCES; AGING RABBIT
AB A reduced sinoatrial node (SAN) functional reserve underlies the age-associated decline in heart rate acceleration in response to stress. SAN cell function involves an oscillatory coupled-clock system: the sarcoplasmic reticulum (SR), a Ca2+ clock, and the electrogenic-sarcolemmal membrane clock. Ca2+ activated-calmodulin-adenylyl cyclase/CaMKII-cAMP/PKA-Ca2+ signaling regulated by phosphodiesterase activity drives SAN cells automaticity. SR-generated local calcium releases (LCRs) activate Na+/Ca2+ exchanger in the membrane clock, which initiates the action potential (AP). We hypothesize that SAN cell dysfunctions accumulate with age. We found a reduction in single SAN cell AP firing in aged (20-24 mo) vs. adult (3-4 mo) mice. The sensitivity of the SAN beating rate responses to both muscarinic and adrenergic receptor activation becomes decreased in advanced age. Additionally, age-associated coincident dysfunctions occur stemming from compromised clock functions, including a reduced SR Ca2+ load and a reduced size, number, and duration of spontaneous LCRs. Moreover, the sensitivity of SAN beating rate to a cAMP stress induced by phosphodiesterase inhibitor is reduced, as are the LCR size, amplitude, and number in SAN cells from aged vs. adult mice. These functional changes coincide with decreased expression of crucial SR Ca2+-cycling proteins, including SR Ca2+-ATPase pump, ryanodine receptors, and Na+/Ca2+ exchanger. Thus a deterioration in intrinsic Ca2+ clock kinetics in aged SAN cells, due to deficits in intrinsic SR Ca2+ cycling and its response to a cAMP-dependent pathway activation, is involved in the age-associated reduction in intrinsic resting AP firing rate, and in the reduction in the acceleration of heart rate during exercise.
C1 [Liu, Jie; Sirenko, Syevda; Juhaszova, Magdalena; Sollott, Steven J.; Shukla, Shweta; Yaniv, Yael; Lakatta, Edward G.] NIA, Lab Cardiovasc Sci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Liu, Jie] Univ Sydney, Dept Physiol, Sydney, NSW 2006, Australia.
RP Lakatta, EG (reprint author), NIA, Lab Cardiovasc Sci, Gerontol Res Ctr, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM LakattaE@grc.nia.nih.gov
FU National Institutes of Health, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 62
TC 1
Z9 1
U1 1
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD MAY
PY 2014
VL 306
IS 10
DI 10.1152/ajpheart.00088.2014
PG 13
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA AI5KD
UT WOS:000336904100001
ER
PT J
AU Dobrinskikh, E
Okamura, K
Kopp, JB
Doctor, RB
Blaine, J
AF Dobrinskikh, Evgenia
Okamura, Kayo
Kopp, Jeffrey B.
Doctor, R. Brian
Blaine, Judith
TI Human podocytes perform polarized, caveolae-dependent albumin
endocytosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE albumin; caveoli; endocytosis; podocytes; trafficking
ID GLOMERULAR-BASEMENT-MEMBRANE; PROXIMAL TUBULE CELLS; NEONATAL
FC-RECEPTOR; ENDOTHELIAL-CELLS; MEDIATED UPTAKE; KIDNEY; IGG; RATS;
DEGRADATION; FILTRATION
AB The renal glomerulus forms a selective filtration barrier that allows the passage of water, ions, and small solutes into the urinary space while restricting the passage of cells and macromolecules. The three layers of the glomerular filtration barrier include the vascular endothelium, glomerular basement membrane (GBM), and podocyte epithelium. Podocytes are capable of internalizing albumin and are hypothesized to clear proteins that traverse the GBM. The present study followed the fate of FITC-labeled albumin to establish the mechanisms of albumin endocytosis and processing by podocytes. Confocal imaging and total internal reflection fluorescence microscopy of immortalized human podocytes showed FITC-albumin endocytosis occurred preferentially across the basal membrane. Inhibition of clathrin-mediated endocytosis and caveolae-mediated endocytosis demonstrated that the majority of FITC-albumin entered podocytes through caveolae. Once internalized, FITC-albumin colocalized with EEA1 and LAMP1, endocytic markers, and with the neonatal Fc receptor, a marker for transcytosis. After preloading podocytes with FITC-albumin, the majority of loaded FITC-albumin was lost over the subsequent 60 min of incubation. A portion of the loss of albumin occurred via lysosomal degradation as pretreatment with leupeptin, a lysosomal protease inhibitor, partially inhibited the loss of FITC-albumin. Consistent with transcytosis of albumin, preloaded podocytes also progressively released FITC-albumin into the extracellular media. These studies confirm the ability of podocytes to endocytose albumin and provide mechanistic insight into cellular mechanisms and fates of albumin handling in podocytes.
C1 [Dobrinskikh, Evgenia; Okamura, Kayo; Doctor, R. Brian; Blaine, Judith] Univ Colorado, Aurora, CO USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Blaine, J (reprint author), Div Renal Dis & Hypertens, 12700 E 19th Ave,C281, Aurora, CO 80045 USA.
EM Judith.Blaine@ucdenver.edu
OI Kopp, Jeffrey/0000-0001-9052-186X
FU NIH [DK-080769, DK-080989]; National Institute of Diabetes and Digestive
and Kidney Diseases Intramural Research Program (NIH); NIH/NCRR Colorado
CTSI [UL1 RR-025780]
FX These studies were supported by NIH grants to R. B. Doctor (DK-080769)
and J. Blaine (DK-080989). J. B. Kopp was supported by the National
Institute of Diabetes and Digestive and Kidney Diseases Intramural
Research Program (NIH). Imaging experiments were performed in the
University of Colorado Anschutz Medical Campus Advance Light Microscopy
Core supported in part by NIH/NCRR Colorado CTSI Grant UL1 RR-025780.
NR 47
TC 16
Z9 16
U1 0
U2 13
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 MAY
PY 2014
VL 306
IS 9
BP F941
EP F951
DI 10.1152/ajprenal.00532.2013
PG 11
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA AI4OO
UT WOS:000336844900002
PM 24573386
ER
PT J
AU Bayliss, EA
Bonds, DE
Boyd, CM
Davis, MM
Finke, B
Fox, MH
Glasgow, RE
Goodman, RA
Heurtin-Roberts, S
Lachenmayr, S
Lind, C
Madigan, EA
Meyers, DS
Mintz, S
Nilsen, WJ
Okun, S
Ruiz, S
Salive, ME
Stange, KC
AF Bayliss, Elizabeth A.
Bonds, Denise E.
Boyd, Cynthia M.
Davis, Melinda M.
Finke, Bruce
Fox, Michael H.
Glasgow, Russell E.
Goodman, Richard A.
Heurtin-Roberts, Suzanne
Lachenmayr, Sue
Lind, Cristin
Madigan, Elizabeth A.
Meyers, David S.
Mintz, Suzanne
Nilsen, Wendy J.
Okun, Sally
Ruiz, Sarah
Salive, Marcel E.
Stange, Kurt C.
TI Understanding the Context of Health for Persons With Multiple Chronic
Conditions: Moving From What Is the Matter to What Matters
SO ANNALS OF FAMILY MEDICINE
LA English
DT Article
DE multiple chronic conditions; chronic illness; health services research
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIALS; TEAM SCIENCE;
PRIMARY-CARE; EXTERNAL VALIDITY; BIOPSYCHOSOCIAL MODEL; COMPLEXITY
SCIENCE; PATIENT-CARE; NEED; MULTIMORBIDITY
AB PURPOSE An isolated focus on 1 disease at a time is insufficient to generate the scientific evidence needed to improve the health of persons living with more than 1 chronic condition. This article explores how to bring context into research efforts to improve the health of persons living with multiple chronic conditions (MCC).
METHODS Forty-five experts, including persons with MCC, family and friend caregivers, researchers, policy makers, funders, and clinicians met to critically consider 4 aspects of incorporating context into research on MCC: key contextual factors, needed research, essential research methods for understanding important contextual factors, and necessary partnerships for catalyzing collaborative action in conducting and applying research.
RESULTS Key contextual factors involve complementary perspectives across multiple levels: public policy, community, health care systems, family, and person, as well as the cellular and molecular levels where most research currently is focused. Needed research involves moving from a disease focus toward a person-driven, goal-directed research agenda. Relevant research methods are participatory, flexible, multilevel, quantitative and qualitative, conducive to longitudinal dynamic measurement from diverse data sources, sufficiently detailed to consider what works for whom in which situation, and generative of ongoing communities of learning, living and practice. Important partnerships for collaborative action include cooperation among members of the research enterprise, health care providers, community-based support, persons with MCC and their family and friend caregivers, policy makers, and payers, including government, public health, philanthropic organizations, and the business community.
CONCLUSION Consistent attention to contextual factors is needed to enhance health research for persons with MCC. Rigorous, integrated, participatory, multimethod approaches to generate new knowledge and diverse partnerships can be used to increase the relevance of research to make health care more sustainable, safe, equitable and effective, to reduce suffering, and to improve quality of life.
C1 [Bayliss, Elizabeth A.] Kaiser Permanente, Denver, CO USA.
[Bonds, Denise E.] NHLBI, Bethesda, MD 20892 USA.
[Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Boyd, Cynthia M.] Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Davis, Melinda M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Finke, Bruce] Indian Hlth Serv, Nashville, TN USA.
[Fox, Michael H.; Goodman, Richard A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Glasgow, Russell E.; Heurtin-Roberts, Suzanne] NCI, NIH, Bethesda, MD 20892 USA.
[Glasgow, Russell E.] Univ Colorado, Sch Med, Denver, CO USA.
[Goodman, Richard A.] Dept Hlth & Human Serv, Off Assistant Secretary Hlth, Atlanta, GA USA.
[Lachenmayr, Sue; Ruiz, Sarah] Natl Council Aging, Washington, DC USA.
[Lind, Cristin] Karolinska Inst, Stockholm, Sweden.
[Meyers, David S.] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Okun, Sally] PatientsLikeMe, Cambridge, MA USA.
[Ruiz, Sarah] Univ Chicago, Chicago, IL 60637 USA.
[Salive, Marcel E.] NIA, Bethesda, MD USA.
RP Stange, KC (reprint author), Case Western Reserve Univ, 11000 Cedar Ave,Suite 402, Cleveland, OH 44106 USA.
EM kcs@case.edu
RI Ruiz, Sarah/B-3456-2017
OI Ruiz, Sarah/0000-0002-6428-2321
FU Clinical Research Professorship from the American Cancer Society;
National Cancer Society
FX Dr Stange's time is supported in part by a Clinical Research
Professorship from the American Cancer Society and by the National
Cancer Society through the Intergovernmental Personnel Act.
NR 99
TC 36
Z9 36
U1 7
U2 45
PU ANNALS FAMILY MEDICINE
PI LEAWOOD
PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA
SN 1544-1709
EI 1544-1717
J9 ANN FAM MED
JI Ann. Fam. Med.
PD MAY-JUN
PY 2014
VL 12
IS 3
BP 260
EP 269
DI 10.1370/afm.1643
PG 10
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA AI3YM
UT WOS:000336801800011
PM 24821898
ER
PT J
AU Ma, N
Xiao, H
Marrero, B
Xing, C
Wang, XQ
Zheng, MK
Han, GC
Chen, GJ
Hou, CM
Shen, BF
Li, Y
Wang, RX
Jiang, ZY
AF Ma, Ning
Xiao, He
Marrero, Bernadette
Xing, Chen
Wang, Xiaoqian
Zheng, Mingke
Han, Gencheng
Chen, Guojiang
Hou, Chunmei
Shen, Beifen
Li, Yan
Wang, Renxi
Jiang, Zhenyu
TI Combination of TACI-IgG and anti-IL-15 treats murine lupus by reducing
mature and memory B cells
SO CELLULAR IMMUNOLOGY
LA English
DT Article
DE TACI-IgG; IL-15; Lupus; Memory B cells
ID AUTOIMMUNE-DISEASE; LYMPHOCYTE STIMULATOR; RHEUMATOID-ARTHRITIS;
T-CELLS; INTERLEUKIN-15; ERYTHEMATOSUS; IL-15; BAFF; MICE
AB Clinical trials suggest that BAFF inhibitors such as atacicept (TACI-IgG) and belimumab (anti-BAFF antibody) could not reduce memory B-cell numbers, although they reduced the numbers of CD20(+) naive B cells and activated B cells. In the present study, we explored the way to reduce memory B-cell numbers. First, we used TACI-IgG to treat murine lupus. We found that TACI-IgG was effective in reducing mature B cell numbers. Accordingly it controlled the level of the anti-dsDNA antibody in lupus-like mice. In addition, TACI-IgG up-regulated memory B cells in murine lupus. Furthermore, we found that TACI-IgG up-regulated IL-15 expression in lupus-like mice. Thus, the combination of TACI-IgG and anti-IL-15 antibodies was explored to understand their effects on the treatment of murine lupus. Compared to treatments with TACI-IgG or anti-IL-15 alone, the combination of TACI-IgG and anti-IL-15 antibodies efficiently ameliorated murine lupus phenotypes. The study provides hints for the clinical application of BAFF- and IL-15-specific therapeutic agents. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Ma, Ning; Jiang, Zhenyu] Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Peoples R China.
[Ma, Ning; Xiao, He; Xing, Chen; Wang, Xiaoqian; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi] Inst Basic Med Sci, Immunol Lab, Beijing 100850, Peoples R China.
[Marrero, Bernadette] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Zheng, Mingke] Henan Univ, Coll Med, Dept Immunol, Kaifeng 475001, Peoples R China.
RP Jiang, ZY (reprint author), Jilin Univ, Hosp 1, Dept Rheumatol, Changchun 130021, Peoples R China.
EM jlujzy@yahoo.com.cn
FU National Basic Research Program 973 Grants [2013CB530506]; Beijing
Natural Science Foundation [7132139]
FX This study was supported by National Basic Research Program 973 Grants
(2013CB530506) and Beijing Natural Science Foundation (7132139). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 20
TC 6
Z9 6
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 0008-8749
EI 1090-2163
J9 CELL IMMUNOL
JI Cell. Immunol.
PD MAY-JUN
PY 2014
VL 289
IS 1-2
BP 140
EP 144
DI 10.1016/j.cellimm.2014.03.017
PG 5
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA AI7ZG
UT WOS:000337120900021
PM 24791699
ER
PT J
AU Yang, TH
Shen, JB
Yang, RH
Redden, J
Dodge-Kafka, K
Grady, J
Jacobson, KA
Liang, BT
AF Yang, Tiehong
Shen, Jian-bing
Yang, Ronghua
Redden, John
Dodge-Kafka, Kimberly
Grady, James
Jacobson, Kenneth A.
Liang, Bruce T.
TI Novel Protective Role of Endogenous Cardiac Myocyte P2X4 Receptors in
Heart Failure
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; myocytes, cardiac; purines
ID NITRIC-OXIDE SYNTHASE; CARDIOMYOCYTE-SPECIFIC OVEREXPRESSION; P2X(4)
RECEPTORS; PRESSURE-OVERLOAD; PURINERGIC RECEPTORS; REPERFUSION INJURY;
MICE; HYPERTROPHY; ATP; CLASSIFICATION
AB Background-Heart failure (HF), despite continuing progress, remains a leading cause of mortality and morbidity. P2X4 receptors (P2X4R) have emerged as potentially important molecules in regulating cardiac function and as potential targets for HF therapy. Transgenic P2X4R overexpression can protect against HF, but this does not explain the role of native cardiac P2X4R. Our goal is to define the physiological role of endogenous cardiac myocyte P2X4R under basal conditions and during HF induced by myocardial infarction or pressure overload.
Methods and Results-Mice established with conditional cardiac-specific P2X4R knockout were subjected to left anterior descending coronary artery ligation-induced postinfarct or transverse aorta constriction-induced pressure overload HF. Knockout cardiac myocytes did not show P2X4R by immunoblotting or by any response to the P2X4R-specific allosteric enhancer ivermectin. Knockout hearts showed normal basal cardiac function but depressed contractile performance in postinfarct and pressure overload models of HF by in vivo echocardiography and ex vivo isolated working heart parameters. P2X4R coimmunoprecipitated and colocalized with nitric oxide synthase 3 (eNOS) in wild-type cardiac myocytes. Mice with cardiac-specific P2X4R overexpression had increased S-nitrosylation, cyclic GMP, NO formation, and were protected from postinfarct and pressure overload HF. Inhibitor of eNOS, L-N-5-(1-iminoethyl) ornithine hydrochloride, blocked the salutary effect of cardiac P2X4R overexpression in postinfarct and pressure overload HF as did eNOS knockout.
Conclusions-This study establishes a new protective role for endogenous cardiac myocyte P2X4R in HF and is the first to demonstrate a physical interaction between the myocyte receptor and eNOS, a mediator of HF protection.
C1 [Yang, Tiehong; Shen, Jian-bing; Yang, Ronghua; Redden, John; Dodge-Kafka, Kimberly; Grady, James; Liang, Bruce T.] Univ Connecticut, Med Ctr, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT 06032 USA.
[Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Liang, BT (reprint author), Univ Connecticut, Med Ctr, Calhoun Cardiol Ctr, 263 Farmington Ave,MC3946, Farmington, CT 06032 USA.
EM bliang@uchc.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institutes of Health [HL48225]; National Institute of Diabetes
and Digestive and Kidney Diseases Intramural Research Program
FX This work was supported by National Institutes of Health grant HL48225
and the National Institute of Diabetes and Digestive and Kidney Diseases
Intramural Research Program.
NR 33
TC 8
Z9 8
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD MAY
PY 2014
VL 7
IS 3
BP 510
EP U252
DI 10.1161/CIRCHEARTFAILURE.113.001023
PG 27
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI3WV
UT WOS:000336796900018
PM 24622244
ER
PT J
AU Garvey, B
Turkbey, B
Truong, H
Bernardo, M
Periaswamy, S
Choyke, PL
AF Garvey, Brian
Tuerkbey, Baris
Truong, Hong
Bernardo, Marcelino
Periaswamy, Senthil
Choyke, Peter L.
TI Clinical value of prostate segmentation and volume determination on MRI
in benign prostatic hyperplasia
SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
ID MAGNETIC-RESONANCE; TRANSRECTAL ULTRASOUND; TRANSITION ZONE; AUTOMATIC
SEGMENTATION; TISSUE COMPOSITION; RESIDUAL URINE; MEN; FINASTERIDE;
IMAGES; AGE
AB Benign prostatic hyperplasia (BPH) is a nonmalignant pathological enlargement of the prostate, which occurs primarily in the transitional zone. BPH is highly prevalent and is a major cause of lower urinary tract symptoms in aging males, although there is no direct relationship between prostate volume and symptom severity. The progression of BPH can be quantified by measuring the volumes of the whole prostate and its zones, based on image segmentation on magnetic resonance imaging. Prostate volume determination via segmentation is a useful measure for patients undergoing therapy for BPH. However, prostate segmentation is not widely used due to the excessive time required for even experts to manually map the margins of the prostate. Here, we review and compare new methods of prostate volume segmentation using both manual and automated methods, including the ellipsoid formula, manual planimetry, and semiautomated and fully automated segmentation approaches. We highlight the utility of prostate segmentation in the clinical context of assessing BPH.
C1 [Garvey, Brian; Tuerkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Truong, Hong] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Periaswamy, Senthil] iCAD Inc, Nashua, NH USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
EM bturkbey@yahoo.com
NR 37
TC 2
Z9 2
U1 0
U2 1
PU AVES
PI FINDIKZADE
PA IBRAHIM KARA, KIZILELMA CAD 5-3, FINDIKZADE, ISTANBUL 34096, TURKEY
SN 1305-3825
EI 1305-3612
J9 DIAGN INTERV RADIOL
JI Diagn. Interv. Radiol.
PD MAY
PY 2014
VL 20
IS 3
BP 229
EP 233
DI 10.5152/dir.2014.13322
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI8OC
UT WOS:000337177600005
PM 24675166
ER
PT J
AU Hong, CW
Walton-Diaz, A
Rais-Bahrami, S
Hoang, AN
Turkbey, B
Stamatakis, L
Xu, S
Amalou, H
Siddiqui, MM
Nix, JW
Vourganti, S
Merino, MJ
Choyke, PL
Wood, BJ
Pinto, PA
AF Hong, Cheng William
Walton-Diaz, Annerleim
Rais-Bahrami, Soroush
Hoang, Anthony N.
Tuerkbey, Baris
Stamatakis, Lambros
Xu, Sheng
Amalou, Hayet
Siddiqui, M. Minhaj
Nix, Jeffrey W.
Vourganti, Srinivas
Merino, Maria J.
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI Imaging and pathology findings after an initial negative MRI-US
fusion-guided and 12-core extended sextant prostate biopsy session
SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID TRANSRECTAL ULTRASOUND BIOPSY; ACTIVE SURVEILLANCE; CANCER
AB PURPOSE A magnetic resonance imaging-ultrasonography (MRI-US) fusion-guided prostate biopsy increases detection rates compared to an extended sextant biopsy. The imaging characteristics and pathology outcomes of subsequent biopsies in patients with initially negative MRI-US fusion biopsies are described in this study.
MATERIALS AND METHODS We reviewed 855 biopsy sessions of 751 patients (June 2007 to March 2013). The fusion biopsy consisted of two cores per lesion identified on multiparametric MRI (mpMRI) and a 12-core extended sextant transrectal US (TRUS) biopsy. Inclusion criteria were at least two fusion biopsy sessions, with a negative first biopsy and mpMRI before each.
RESULTS The detection rate on the initial fusion biopsy was 55.3%; 336 patients had negative findings. Forty-one patients had follow-up fusion biopsies, but only 34 of these were preceded by a repeat mpMRI. The median interval between biopsies was 15 months. Fourteen patients (41%) were positive for cancer on the repeat MRI-US fusion biopsy. Age, prostate- specific antigen (PSA), prostate volume, PSA density, digital rectal exam findings, lesion diameter, and changes on imaging were comparable between patients with negative and positive rebiopsies. Of the patients with positive rebiopsies, 79% had a positive TRUS biopsy before referral (P = 0.004). Ten patients had Gleason 3+3 disease, three had 3+4 disease, and one had 4+4 disease.
CONCLUSION In patients with a negative MRI-US fusion prostate biopsy and indications for repeat biopsy, the detection rate of the follow-up sessions was lower than the initial detection rate. Of the prostate cancers subsequently found, 93% were low grade (<= 3+4). In this low risk group of patients, increasing the follow-up time interval should be considered in the appropriate clinical setting.
C1 [Hong, Cheng William; Xu, Sheng; Amalou, Hayet; Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
[Walton-Diaz, Annerleim; Rais-Bahrami, Soroush; Hoang, Anthony N.; Stamatakis, Lambros; Siddiqui, M. Minhaj; Nix, Jeffrey W.; Vourganti, Srinivas; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Tuerkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Hong, CW (reprint author), NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
EM williamhongcheng@gmail.com
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU Intramural NIH HHS [ZIA CL040011-06]
NR 23
TC 4
Z9 4
U1 0
U2 1
PU AVES
PI FINDIKZADE
PA IBRAHIM KARA, KIZILELMA CAD 5-3, FINDIKZADE, ISTANBUL 34096, TURKEY
SN 1305-3825
EI 1305-3612
J9 DIAGN INTERV RADIOL
JI Diagn. Interv. Radiol.
PD MAY
PY 2014
VL 20
IS 3
BP 234
EP 238
DI 10.5152/dir.2014.13345
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI8OC
UT WOS:000337177600006
PM 24509182
ER
PT J
AU Jin, GX
Wong, STC
AF Jin, Guangxu
Wong, Stephen T. C.
TI Toward better drug repositioning: prioritizing and integrating existing
methods into efficient pipelines
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID OFF-LABEL USE; INTERACTION DATABASE; CONNECTIVITY MAP; ONCOLOGY DRUGS;
LIGAND DATABASE; MICROARRAY DATA; DISCOVERY; TARGET; INHIBITORS;
NETWORKS
AB Recycling old drugs, rescuing shelved drugs and extending patents' lives make drug repositioning an attractive form of drug discovery. Drug repositioning accounts for approximately 30% of the newly US Food and Drug Administration (FDA)-approved drugs and vaccines in recent years. The prevalence of drug-repositioning studies has resulted in a variety of innovative computational methods for the identification of new opportunities for the use of old drugs. Questions often arise from customizing or optimizing these methods into efficient drug-repositioning pipelines for alternative applications. It requires a comprehensive understanding of the available methods gained by evaluating both biological and pharmaceutical knowledge and the elucidated mechanism-of-action of drugs. Here, we provide guidance for prioritizing and integrating drug-repositioning methods for specific drug-repositioning pipelines.
C1 [Jin, Guangxu; Wong, Stephen T. C.] Weill Cornell Med Coll, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA.
[Jin, Guangxu; Wong, Stephen T. C.] Houston Methodist Res Inst, NCI Ctr Modeling Canc Dev, Houston, TX 77030 USA.
RP Wong, STC (reprint author), Weill Cornell Med Coll, Houston Methodist Res Inst, Dept Syst Med & Bioengn, Houston, TX 77030 USA.
EM stwong@tmhs.org
FU National Institutes of Health (NIH) [U54 CA149196]; National Cancer
Institute (NCI) [CA121225]; John S. Dunn Research Foundation; Chao
Foundation grant
FX This research is funded by the National Institutes of Health (NIH) U54
CA149196, National Cancer Institute (NCI) CA121225, a John S. Dunn
Research Foundation grant and a T.T. & W.F. Chao Foundation grant to
S.T.C.W. The authors would like to thank Rebecca Danforth for
proofreading the manuscript.
NR 65
TC 64
Z9 65
U1 4
U2 35
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
EI 1878-5832
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD MAY
PY 2014
VL 19
IS 5
BP 637
EP 644
DI 10.1016/j.drudis.2013.11.005
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AI5ZL
UT WOS:000336949400012
PM 24239728
ER
PT J
AU Doimo, NTS
Zarate-Blades, CR
Rodrigues, RF
Tefe-Silva, C
Trotte, MNS
Souza, PRM
Soares, LS
Rios, WM
Floriano, EM
Brandao, IT
Masson, AP
Coelho, V
Ramos, SG
Silva, CL
AF Doimo, Nayara T. S.
Zarate-Blades, Carlos R.
Rodrigues, Rodrigo F.
Tefe-Silva, Cristiane
Trotte, Marcele N. S.
Souza, Patricia R. M.
Soares, Luana S.
Rios, Wendy M.
Floriano, Elaine M.
Brandao, Izaira T.
Masson, Ana P.
Coelho, Veronica
Ramos, Simone G.
Silva, Celio L.
TI Immunotherapy of tuberculosis with Mycobacterium leprae Hsp65 as a DNA
vaccine triggers cross-reactive antibodies against mammalian Hsp60 but
not pathological autoimmunity
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Article
DE tuberculosis; autoimmune response; heat-shock protein; DNA vaccine;
immunotherapy
ID T-CELLS; MICE; PATHOGENESIS; THERAPY; LUNG; IDENTIFICATION; EXPRESSION;
INFECTION; ARTHRITIS; GAMMA
AB Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy.
C1 [Doimo, Nayara T. S.; Zarate-Blades, Carlos R.; Rodrigues, Rodrigo F.; Souza, Patricia R. M.; Soares, Luana S.; Rios, Wendy M.; Brandao, Izaira T.; Masson, Ana P.; Silva, Celio L.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, Ctr TB Res, Sao Paulo, Brazil.
[Tefe-Silva, Cristiane; Floriano, Elaine M.; Ramos, Simone G.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pathol, Sao Paulo, Brazil.
[Trotte, Marcele N. S.] Univ Estado Rio De Janeiro, Vet Med Dept Anat Pathol, Rio De Janeiro, Brazil.
[Coelho, Veronica] Univ Sao Paulo, Sch Med, Heart Inst InCor, Immunol Lab, Sao Paulo, Brazil.
[Coelho, Veronica] NIST, Inst Invest Immunol 3, Sao Paulo, Brazil.
RP Zarate-Blades, CR (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM crzblades@usp.br; clsilva@fmrp.usp.br
RI Zarate-Blades, Carlos/C-9663-2015; Silva, Celio/C-4639-2012
OI Zarate-Blades, Carlos/0000-0002-7728-7869;
FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP
[2009/06793-7]
FX This research received support from Fundacao de Amparo a Pesquisa do
Estado de Sao Paulo, FAPESP (Grant number 2009/06793-7). We thank Dr
Carlos A Mandarim-de-Lacerda for excellent discussion prior initiation
of the study.
NR 36
TC 2
Z9 3
U1 1
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD MAY
PY 2014
VL 10
IS 5
BP 1238
EP 1243
DI 10.4161/hv.28249
PG 6
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA AI2AA
UT WOS:000336656700022
PM 24607935
ER
PT J
AU Del Fiol, G
Workman, TE
Gorman, PN
AF Del Fiol, Guilherme
Workman, T. Elizabeth
Gorman, Paul N.
TI Clinical Questions Raised by Clinicians at the Point of Care A
Systematic Review
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID INFORMATION-SEEKING BEHAVIOR; PATIENT-CARE; HEALTH-CARE; FAMILY
PHYSICIANS; MEDICAL INFORMATION; ONLINE EVIDENCE; NEEDS; KNOWLEDGE;
RESIDENTS; ANSWERS
AB IMPORTANCE In making decisions about patient care, clinicians raise questions and are unable to pursue or find answers to most of them. Unanswered questions may lead to suboptimal patient care decisions.
OBJECTIVE To systematically review studies that examined the questions clinicians raise in the context of patient care decision making.
DATA SOURCES MEDLINE (from 1966), CINAHL (from 1982), and Scopus (from 1947), all through May 26, 2011.
STUDY SELECTION Studies that examined questions raised and observed by clinicians (physicians, medical residents, physician assistants, nurse practitioners, nurses, dentists, and care managers) in the context of patient care were independently screened and abstracted by 2 investigators. Of 21 710 citations, 72 met the selection criteria.
DATA EXTRACTION AND SYNTHESIS Question frequency was estimated by pooling data from studies with similar methods.
MAIN OUTCOMES AND MEASURES Frequency of questions raised, pursued, and answered and questions by type according to a taxonomy of clinical questions. Thematic analysis of barriers to information seeking and the effects of information seeking on decision making.
RESULTS In 11 studies, 7012 questions were elicited through short interviews with clinicians after each patient visit. The mean frequency of questions raised was 0.57 (95% CI, 0.38-0.77) per patient seen, and clinicians pursued 51%(36%-66%) of questions and found answers to 78%(67%-88%) of those they pursued. Overall, 34% of questions concerned drug treatment, and 24% concerned potential causes of a symptom, physical finding, or diagnostic test finding. Clinicians' lack of time and doubt that a useful answer exists were the main barriers to information seeking.
CONCLUSIONS AND RELEVANCE Clinicians frequently raise questions about patient care in their practice. Although they are effective at finding answers to questions they pursue, roughly half of the questions are never pursued. This picture has been fairly stable over time despite the broad availability of online evidence resources that can answer these questions. Technology-based solutions should enable clinicians to track their questions and provide just-in-time access to high-quality evidence in the context of patient care decision making. Opportunities for improvement include the recent adoption of electronic health record systems and maintenance of certification requirements.
C1 [Del Fiol, Guilherme] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84108 USA.
[Workman, T. Elizabeth] Natl Lib Med, Lister Hill Ctr, Bethesda, MD USA.
[Gorman, Paul N.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA.
RP Del Fiol, G (reprint author), Univ Utah, Dept Biomed Informat, 421 Wakara Way,Ste 140, Salt Lake City, UT 84108 USA.
EM guilherme.delfiol@utah.edu
OI Del Fiol, Guilherme/0000-0001-9954-6799
FU Agency for Healthcare Research and Quality [K01HS018352]
FX This project was supported by the Agency for Healthcare Research and
Quality (grant K01HS018352).
NR 80
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Z9 28
U1 4
U2 27
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAY
PY 2014
VL 174
IS 5
BP 710
EP 718
DI 10.1001/jamainternmed.2014.368
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4NS
UT WOS:000336842700013
PM 24663331
ER
PT J
AU Bonds, DE
Harrington, M
Worrall, BB
Bertoni, AG
Eaton, CB
Hsia, J
Robinson, J
Clemons, TE
Fine, LJ
Chew, EY
AF Bonds, Denise E.
Harrington, Molly
Worrall, Bradford B.
Bertoni, Alain G.
Eaton, Charles B.
Hsia, Judy
Robinson, Jennifer
Clemons, Traci E.
Fine, Lawrence J.
Chew, Emily Y.
CA AREDS2 Res Grp
TI Effect of Long-Chain omega-3 Fatty Acids and Lutein plus Zeaxanthin
Supplements on Cardiovascular Outcomes Results of the Age-Related Eye
Disease Study 2 (AREDS2) Randomized Clinical Trial
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID N-3 FATTY-ACIDS; MYOCARDIAL-INFARCTION; FISH CONSUMPTION; B-VITAMINS;
RISK; DEATH; ATHEROSCLEROSIS; ASSOCIATION; DYSGLYCEMIA; CAROTENOIDS
AB IMPORTANCE Dietary supplements have been proposed as a mechanism to improve health and prevent disease.
OBJECTIVE To determine if supplementing diet with long-chain omega-3 polyunsaturated fatty acids or with macular xanthophylls results in a reduced rate of cardiovascular disease (CVD).
DESIGN, SETTING, AND PARTICIPANTS The Cardiovascular Outcome Study (COS) was an ancillary study of the Age-Related Eye Disease Study 2 (AREDS2), a factorial-designed randomized clinical trial of 4203 participants recruited from 82 US academic and community ophthalmology clinics, who were followed up for a median of 4.8 years. Individuals were eligible to participate if they were between the ages of 50 and 85 years, had intermediate or advanced age-related macular degeneration in 1 eye, and were willing to be randomized. Participants with stable, existing CVD (>12 months since initial event) were eligible to participate. Participants, staff, and outcome assessors were masked to intervention.
INTERVENTIONS Daily supplementation with long-chain omega-3 polyunsaturated fatty acids (350-mg docosahexaenoic acid [DHA] + 650-mg eicosapentaenoic acid [EPA]), macular xanthophylls (10-mg lutein + 2-mg zeaxanthin), combination of the two, or matching placebos. These treatments were added to background therapy of the AREDS vitamin and mineral formulation for macular degeneration.
MAIN OUTCOMES AND MEASURES A composite outcome of myocardial infarction, stroke, and cardiovascular death with 4 prespecified secondary combinations of the primary outcome with hospitalized heart failure, revascularization, or unstable angina.
RESULTS Study participants were primarily white, married, and highly educated, with a median age at baseline of 74 years. A total of 602 cardiovascular events were adjudicated, and 459 were found to meet 1 of the study definitions for a CVD outcome. In intention-to-treat analysis, no reduction in the risk of CVD or secondary CVD outcomes was seen for the DHA + EPA (primary outcome: hazard ratio [HR], 0.95; 95% CI, 0.78-1.17) or lutein + zeaxanthin (primary outcome: HR, 0.94; 95% CI, 0.77-1.15) groups. No differences in adverse events or serious adverse event were seen by treatment group. The sample size was sufficient to detect a 25% reduction in CVD events with 80% power.
CONCLUSIONS AND RELEVANCE Dietary supplementation of long-chain omega-3 polyunsaturated fatty acids or macular xanthophylls in addition to daily intake of minerals and vitamins did not reduce the risk of CVD in elderly participants with age-related macular degeneration.
C1 [Bonds, Denise E.; Fine, Lawrence J.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Harrington, Molly; Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
[Worrall, Bradford B.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA.
[Bertoni, Alain G.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[Eaton, Charles B.] Alpert Med Sch, Div Biol & Med, Dept Family Med & Epidemiol, Providence, RI USA.
[Eaton, Charles B.] Brown Univ, Sch Publ Hlth, Providence, RI 02912 USA.
[Hsia, Judy] AstraZeneca LLP, Washington, DC USA.
[Robinson, Jennifer] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Robinson, Jennifer] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
[Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Bonds, DE (reprint author), NHLBI, Rockledge Ctr 2, MSC 7936,6701 Rockledge Dr,Ste 10018, Bethesda, MD 20892 USA.
EM bondsde@nhlbi.nih.gov
FU National Eye Institute/National Institutes of Health, Department of
Health and Human Services [HHS-N-260-2005-00007-C]; ADB [N01-EY-5-0007];
National Institutes of Health (NIH): Office of Dietary Supplements;
National Center for Complementary and Alternative Medicine, National
Institute on Aging, National Heart, Lung, and Blood Institute; National
Institute of Neurological Disorders and Stroke
FX The AREDS2 study is supported by the intramural program funds and
contracts from the National Eye Institute/National Institutes of Health,
Department of Health and Human Services (contract No.
HHS-N-260-2005-00007-C and ADB contract No. N01-EY-5-0007). Funds were
generously contributed to these contracts by the following National
Institutes of Health (NIH): Office of Dietary Supplements, National
Center for Complementary and Alternative Medicine, National Institute on
Aging, National Heart, Lung, and Blood Institute, and National Institute
of Neurological Disorders and Stroke.
NR 21
TC 22
Z9 22
U1 5
U2 24
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD MAY
PY 2014
VL 174
IS 5
BP 763
EP 771
DI 10.1001/jamainternmed.2014.328
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA AI4NS
UT WOS:000336842700023
ER
PT J
AU Dutton-Regester, K
Gartner, JJ
Emmanuel, R
Qutob, N
Davies, MA
Gershenwald, JE
Robinson, W
Robinson, S
Steven, AR
Scolyer, RA
Mann, GJ
Thompson, JF
Hayward, NK
Samuels, Y
AF Dutton-Regester, Ken
Gartner, Jared J.
Emmanuel, Rafi
Qutob, Nouar
Davies, Michael A.
Gershenwald, Jeffrey E.
Robinson, William
Robinson, Steven
Steven, A. Rosenberg
Scolyer, Richard A.
Mann, Graham J.
Thompson, John F.
Hayward, Nicholas K.
Samuels, Yardena
TI A highly recurrent RPS27 5 ' UTR mutation in melanoma
SO ONCOTARGET
LA English
DT Article
DE Melanoma; somatic mutation; RPS27; exome sequencing; 5 ' untranslated
region
ID TOP MESSENGER-RNAS; TRANSLATIONAL CONTROL; OLIGOPYRIMIDINE-TRACT;
CANCER-THERAPY; PHASE-I; PROTEIN; GENOME; MTOR; METALLOPROTEINASE;
INHIBITION
AB The incidence of melanoma continues to rise globally and is increasing at a rate greater than any other cancer. To systematically search for new genes involved in melanomagenesis, we collated exome sequencing data from independent melanoma cohort datasets, including those in the public domain. We identified recurrent mutations that may drive melanoma growth, survival or metastasis, and which may hold promise for the design of novel therapies to treat melanoma. These included a frequent recurrent (i.e. hotspot) mutation in the 5' untranslated region of RPS27 in similar to 10% of samples. We show that the mutation expands the 5'TOP element, a motif known to regulate the expression of most of the ribosomal protein family, to which RPS27 belongs, and thus might sensitize the mutated transcript to growth-mediated regulation. This finding highlights not only the important role of non-protein coding genetic aberrations in cancer development but also their potential as novel therapeutic targets.
C1 [Dutton-Regester, Ken; Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Gartner, Jared J.; Steven, A. Rosenberg] NCI, NIH, Bethesda, MD 20892 USA.
[Emmanuel, Rafi; Qutob, Nouar; Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Davies, Michael A.; Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Robinson, William; Robinson, Steven] Univ Colorado, Sch Med, Aurora, CO USA.
[Scolyer, Richard A.; Mann, Graham J.; Thompson, John F.] Melanoma Inst Australia, Sydney, NSW, Australia.
[Scolyer, Richard A.] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia.
[Scolyer, Richard A.] Univ Sydney, Discipline Pathol, Sydney, NSW 2006, Australia.
[Mann, Graham J.] Univ Sydney, Westmead Millenium Inst, Westmead, NSW 2145, Australia.
[Thompson, John F.] Dept Melanoma, Sydney, NSW, Australia.
[Thompson, John F.] Dept Surg Oncol, Sydney, NSW, Australia.
[Thompson, John F.] Royal Prince Alfred Hosp, Sydney, NSW, Australia.
[Thompson, John F.] Univ Sydney, Discipline Surg, Sydney Med Sch, Sydney, NSW 2006, Australia.
RP Samuels, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
EM Nicholas.Hayward@qimrberghofer.edu.au; Yardena.Samuels@weizmann.ac.il
RI hayward, nicholas/C-1367-2015;
OI hayward, nicholas/0000-0003-4760-1033; Scolyer,
Richard/0000-0002-8991-0013
FU National Human Genome Research Institute; National Institutes of Health,
USA; University of Texas MD Anderson Cancer Center Melanoma SPORE
[P50CA093459]; National Health and Medical Research Council (NHMRC) of
Australia; Israel Science Foundation [1604/13, 877/13]; ERC
[StG-335377]; Dukler Fund for Cancer Research; Comisaroff Family Trust;
NHRMC; Gideon Hamburger, Israel
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute, National Institutes of Health,
USA, The University of Texas MD Anderson Cancer Center Melanoma SPORE
(P50CA093459) and the National Health and Medical Research Council
(NHMRC) of Australia. YS is supported by the Israel Science Foundation
grant numbers 1604/13 and 877/13, the ERC (StG-335377), Dukler Fund for
Cancer Research, Comisaroff Family Trust and Gideon Hamburger, Israel.
NKH and KD-R are supported by fellowships from the NHRMC. The authors
gratefully acknowledge the assistance of Gulietta Pupo, Varsha Tembe,
Candace Carter and other colleagues from Melanoma Institute Australia,
Royal Prince Alfred Hospital and Westmead Millennium Institute, Sydney,
Australia.
NR 38
TC 13
Z9 14
U1 0
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAY
PY 2014
VL 5
IS 10
BP 2912
EP 2917
PG 6
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AI6FL
UT WOS:000336967000004
PM 24913145
ER
PT J
AU Sequeira, G
Vanzulli, SI
Rojas, P
Lamb, C
Colombo, L
May, M
Molinolo, A
Lanari, C
AF Sequeira, Gonzalo
Vanzulli, Silvia I.
Rojas, Paola
Lamb, Caroline
Colombo, Lucas
May, Maria
Molinolo, Alfredo
Lanari, Claudia
TI The effectiveness of nano chemotherapeutic particles combined with
mifepristone depends on the PR isoform ratio in preclinical models of
breast cancer
SO ONCOTARGET
LA English
DT Article
DE breast cancer; PR isoforms; doxorubicin; paclitaxel; mifepristone;
mammary carcinomas; Nab-paclitaxel; pegylated doxorubicin liposomes
ID PROGESTERONE-RECEPTOR ISOFORMS; ALBUMIN-BOUND PACLITAXEL; PHASE-III
TRIAL; MAMMARY CARCINOMAS; TUMOR-REGRESSION; GENE-REGULATION;
CREMOPHOR-FREE; DOXORUBICIN; TAXOL; CELLS
AB There is clinical and experimental evidence suggesting that antiprogestins might be used for the treatment of selected breast cancer patients. Our aim was to evaluate the effect of albumin-bound paclitaxel (Nab-paclitaxel) and pegylated doxorubicin liposomes (PEG-LD) in combination with mifepristone (MFP) in experimental breast cancer models expressing different ratios of progesterone receptor (PR) isoforms A and B. We used two antiprogestin-responsive (PRA>PRB) and two resistant (PRA50% of tumor cells in a majority of ASs but only in 7% of EHEs. None of the 55 ASs studied were immunohistochemically positive for TIA-1 or Granzyme B, antigens used as more specific markers for anaplastic large-cell lymphoma. Compared with AS, normal vascular endothelia of capillaries and muscular vessels showed variable positivity. Among hemangiomas, cavernous and spindle cell hemangiomas showed most frequent endothelial CD30 positivity, whereas in most other hemangiomas, CD30 positivity was scant. In conclusion, CD30 expression occurs in a significant subset of ASs and EHEs and needs to be included in the differential diagnosis with other CD30-positive malignancies to avoid a diagnostic pitfall. It remains to be determined whether patients with strongly CD30-positive ASs could be candidates for targeted therapy using the recently introduced CD30 antibody drug conjugates.
C1 [Alimchandani, Meghna; Wang, Zeng-Feng; Miettinen, Markku] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Miettinen, M (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10-2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI's Intramural Research Program
FX Supported as a part of NCI's Intramural Research Program.
NR 28
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1541-2016
EI 1533-4058
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD MAY-JUN
PY 2014
VL 22
IS 5
BP 358
EP 362
DI 10.1097/PAI.0000000000000048
PG 5
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA AI3FI
UT WOS:000336745600006
PM 24805132
ER
PT J
AU Wu, XS
Zhang, Z
Zhao, WD
Wang, DS
Luo, FJ
Wu, LG
AF Wu, Xin-Sheng
Zhang, Zhen
Zhao, Wei-Dong
Wang, Dongsheng
Luo, Fujun
Wu, Ling-Gang
TI Calcineurin Is Universally Involved in Vesicle Endocytosis at Neuronal
and Nonneuronal Secretory Cells
SO CELL REPORTS
LA English
DT Article
ID ADRENAL CHROMAFFIN CELLS; NERVE-TERMINALS; SYNAPTIC VESICLES;
SYNAPTOTAGMIN-I; SLOW ENDOCYTOSIS; CALCIUM; EXOCYTOSIS; SYNAPSES;
RELEASE; CALYX
AB Calcium influx triggers and accelerates endocytosis in nerve terminals and nonneuronal secretory cells. Whether calcium/calmodulin-activated calcineurin, which dephosphorylates endocytic proteins, mediates this process is highly controversial for different cell types, developmental stages, and endocytic forms. Using three preparations that previously produced discrepant results (i.e., large calyx-type synapses, conventional cerebellar synapses, and neuroendocrine chromaffin cells containing large dense-core vesicles), we found that calcineurin gene knockout consistently slowed down endocytosis, regardless of cell type, developmental stage, or endocytic form (rapid or slow). In contrast, calcineurin and calmodulin blockers slowed down endocytosis at a relatively small calcium influx, but did not inhibit endocytosis at a large calcium influx, resulting in false-negative results. These results suggest that calcineurin is universally involved in endocytosis. They may also help explain the discrepancies among previous pharmacological studies. We therefore suggest that calcineurin should be included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis.
C1 [Wu, Xin-Sheng; Zhang, Zhen; Zhao, Wei-Dong; Wang, Dongsheng; Luo, Fujun; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA.
RP Wu, LG (reprint author), NINDS, Bethesda, MD 20892 USA.
EM wul@ninds.nih.gov
FU National Institute of Neurological Disorders; Stroke Intramural Research
Program
FX We thank Drs. Jonathan G. Seidman (Harvard Medical School) and Jennifer
L. Gooch (Emory University School of Medicine) for providing CaN
Aalpha+/- mice, and Dr. Yong-Ling Zhu
(Northwestern University) for providing the SypH2X construct. We thank
Dr. Edaeni Hamid for commenting on the manuscript. This work was
supported by the National Institute of Neurological Disorders and Stroke
Intramural Research Program.
NR 33
TC 13
Z9 13
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAY
PY 2014
VL 7
IS 4
BP 982
EP 988
DI 10.1016/j.celrep.2014.04.020
PG 7
WC Cell Biology
SC Cell Biology
GA AH9WL
UT WOS:000336495700008
PM 24835995
ER
PT J
AU Kemp, CJ
Moore, JM
Moser, R
Bernard, B
Teater, M
Smith, LE
Rabaia, NA
Gurley, KE
Guinney, J
Busch, SE
Shaknovich, R
Lobanenkov, VV
Liggitt, D
Shmulevich, I
Melnick, A
Filippova, GN
AF Kemp, Christopher J.
Moore, James M.
Moser, Russell
Bernard, Brady
Teater, Matt
Smith, Leslie E.
Rabaia, Natalia A.
Gurley, Kay E.
Guinney, Justin
Busch, Stephanie E.
Shaknovich, Rita
Lobanenkov, Victor V.
Liggitt, Denny
Shmulevich, Ilya
Melnick, Ari
Filippova, Galina N.
TI CTCF Haploinsufficiency Destabilizes DNA Methylation and Predisposes to
Cancer
SO CELL REPORTS
LA English
DT Article
ID PROTEIN CTCF; TRANSCRIPTION FACTOR; BINDING-SITES; GENOME-WIDE; BREAST;
SPECIFICITY; MUTATIONS; GENETICS; GENES; MAP
AB Epigenetic alterations, particularly in DNA methylation, are ubiquitous in cancer, yet the molecular origins and the consequences of these alterations are poorly understood. CTCF, a DNA-binding protein that regulates higher-order chromatin organization, is frequently altered by hemizygous deletion or mutation in human cancer. To date, a causal role for CTCF in cancer has not been established. Here, we show that Ctcf hemizygous knockout mice are markedly susceptible to spontaneous, radiation-, and chemically induced cancer in a broad range of tissues. Ctcf(+/-) tumors are characterized by increased aggressiveness, including invasion, metastatic dissemination, and mixed epithelial/mesenchymal differentiation. Molecular analysis of Ctcf(+/-) tumors indicates that Ctcf is haploinsufficient for tumor suppression. Tissues with hemizygous loss of CTCF exhibit increased variability in CpG methylation genome wide. These findings establish CTCF as a prominent tumor-suppressor gene and point to CTCF-mediated epigenetic stability as a major barrier to neoplastic progression.
C1 [Kemp, Christopher J.; Moore, James M.; Moser, Russell; Smith, Leslie E.; Rabaia, Natalia A.; Gurley, Kay E.; Busch, Stephanie E.; Filippova, Galina N.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
[Bernard, Brady; Shmulevich, Ilya] Inst Syst Biol, Seattle, WA 98106 USA.
[Teater, Matt; Shaknovich, Rita; Melnick, Ari] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY 10021 USA.
[Guinney, Justin] Sage Bionetworks, Seattle, WA 98109 USA.
[Lobanenkov, Victor V.] NIAID, Mol Pathol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Liggitt, Denny] Univ Washington, Dept Comparat Med, Seattle, WA 98195 USA.
RP Kemp, CJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA.
EM cjkemp@fhcrc.org; gfilippo@fhcrc.org
OI Lobanenkov, Victor/0000-0001-6665-3635
FU NIH [CA68360, ES007033, DA030326, U24CA143835, U01 CA141550, U01
CA176303]; NIGMS [PHS NRSA T32 GM007270]
FX This work was supported by NIH grant numbers CA68360, ES007033,
DA030326, U24CA143835, U01 CA141550, U01 CA176303, and PHS NRSA T32
GM007270 from NIGMS. We thank S. Collins, C. Grandori, S. Henikoff, S.
Tapscott, and F. Yang for comments on the manuscript, and the William
Guy Forbeck Research Foundation.
NR 24
TC 29
Z9 29
U1 3
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAY
PY 2014
VL 7
IS 4
BP 1020
EP 1029
DI 10.1016/j.celrep.2014.04.004
PG 10
WC Cell Biology
SC Cell Biology
GA AH9WL
UT WOS:000336495700012
PM 24794443
ER
PT J
AU Portmann, T
Yang, M
Mao, R
Panagiotakos, G
Ellegood, J
Dolen, G
Bader, PL
Grueter, BA
Goold, C
Fisher, E
Clifford, K
Rengarajan, P
Kalikhman, D
Loureiro, D
Saw, NL
Zhou, ZQ
Miller, MA
Lerch, JP
Henkelman, RM
Shamloo, M
Malenka, RC
Crawley, JN
Dolmetsch, RE
AF Portmann, Thomas
Yang, Mu
Mao, Rong
Panagiotakos, Georgia
Ellegood, Jacob
Dolen, Gul
Bader, Patrick L.
Grueter, Brad A.
Goold, Carleton
Fisher, Elaine
Clifford, Katherine
Rengarajan, Pavitra
Kalikhman, David
Loureiro, Darren
Saw, Nay L.
Zhou Zhengqui
Miller, Michael A.
Lerch, Jason P.
Henkelman, R. Mark
Shamloo, Mehrdad
Malenka, Robert C.
Crawley, Jacqueline N.
Dolmetsch, Ricardo E.
TI Behavioral Abnormalities and Circuit Defects in the Basal Ganglia of a
Mouse Model of 16p11.2 Deletion Syndrome
SO CELL REPORTS
LA English
DT Article
ID DEVELOPING CEREBRAL-CORTEX; AUTISM SPECTRUM DISORDERS; SUBTYPE-SPECIFIC
GENES; PROJECTION NEURONS; MOLECULAR SPECIFICATION; NUCLEUS-ACCUMBENS;
PYRAMIDAL NEURONS; TIMOTHY SYNDROME; CORPUS-CALLOSUM; PHENOTYPES
AB A deletion on human chromosome 16p11.2 is associated with autism spectrum disorders. We deleted the syntenic region on mouse chromosome 7F3. MRI and high-throughput single-cell transcriptomics revealed anatomical and cellular abnormalities, particularly in cortex and striatum of juvenile mutant mice (16p11(+/-)). We found elevated numbers of striatal medium spiny neurons (MSNs) expressing the dopamine D2 receptor (Drd2(+)) and fewer dopamine-sensitive (Drd1(+)) neurons in deep layers of cortex. Electrophysiological recordings of Drd2(+) MSN revealed synaptic defects, suggesting abnormal basal ganglia circuitry function in 16p11(+/-) mice. This is further supported by behavioral experiments showing hyperactivity, circling, and deficits in movement control. Strikingly, 16p11(+/-) mice showed a complete lack of habituation reminiscent of what is observed in some autistic individuals. Our findings unveil a fundamental role of genes affected by the 16p11.2 deletion in establishing the basal ganglia circuitry and provide insights in the pathophysiology of autism.
C1 [Portmann, Thomas; Mao, Rong; Panagiotakos, Georgia; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Dolmetsch, Ricardo E.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
[Portmann, Thomas; Mao, Rong; Panagiotakos, Georgia; Bader, Patrick L.; Grueter, Brad A.; Goold, Carleton; Fisher, Elaine; Clifford, Katherine; Rengarajan, Pavitra; Shamloo, Mehrdad; Malenka, Robert C.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Yang, Mu; Kalikhman, David; Loureiro, Darren; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
Stanford Univ, Neurosci Program, Stanford, CA 94305 USA.
[Ellegood, Jacob; Lerch, Jason P.; Henkelman, R. Mark] Hosp Sick Children, Mouse Imaging Ctr MICe, Toronto, ON M5T 3H7, Canada.
[Dolen, Gul] Johns Hopkins Univ, Brain Sci Inst, Dept Neurosci, Baltimore, MD 21205 USA.
[Bader, Patrick L.] Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Grueter, Brad A.; Malenka, Robert C.] Stanford Univ, Dept Psychiat & Behav Sci, Nancy Pritzker Lab, Stanford, CA 94305 USA.
[Saw, Nay L.; Zhou Zhengqui; Miller, Michael A.; Shamloo, Mehrdad] Stanford Behav & Funct Neurosci Lab, Stanford, CA 94305 USA.
[Lerch, Jason P.; Henkelman, R. Mark] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
[Shamloo, Mehrdad] Stanford Inst Neuroinnovat & Translat Neurosci, Stanford, CA 94305 USA.
[Dolmetsch, Ricardo E.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
RP Dolmetsch, RE (reprint author), Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA.
EM ricardo.dolmetsch@novartis.com
RI Dolen, Gul/J-3073-2015; Henkelman, Mark/F-3662-2011;
OI Dolen, Gul/0000-0003-1780-995X; Grueter, Brad/0000-0002-4224-3866
FU Simons foundation SFARI grant [204340]; Nina Jauw; Swiss National
Science Foundation [PBSKP3-123434, PA00P3_134196]; NIMH Intramural
Research Program; University of California Davis MIND Institute; NIMH
[MH09064802]; NIH/NIMH [MH091160]; Institute of Neurological Disorders
and Stroke P30 center core grant [NS06937501A1]
FX We would like to thank Ulrich Elling and Josef Penninger (IMBA Vienna,
Austria) for help and advice on mouse ESC targeting, Marty Bigos of the
Stanford shared FACS facility for assistance with clone sorting, Renee
Reijo-Pera for generously providing the Biomark Instruments, Kristin L.
Sainani for advice in statistical analysis of mouse behavioral data, and
Yishan Sun for validating and providing primer pairs for the single-cell
gene expression analysis. This research was funded by the Simons
foundation SFARI grant no. 204340 (R.E.D. and J.N.C.), Nina Jauw
(R.E.D.), the Swiss National Science Foundation (nos. PBSKP3-123434 and
PA00P3_134196, T. P.), the NIMH Intramural Research Program and the
University of California Davis MIND Institute (M.Y., D.K., D.L., and
J.N.C.), an F31 NRSA from the NIMH (no. MH09064802, G.P.), a K99 from
the NIH/NIMH (no. MH091160, R.M.), and the Institute of Neurological
Disorders and Stroke P30 center core grant no. NS06937501A1 (M.S.).
NR 61
TC 31
Z9 31
U1 2
U2 14
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAY
PY 2014
VL 7
IS 4
BP 1077
EP 1092
DI 10.1016/j.celrep.2014.03.036
PG 16
WC Cell Biology
SC Cell Biology
GA AH9WL
UT WOS:000336495700018
PM 24794428
ER
PT J
AU Ryu, JY
Galan, AK
Xin, XB
Dong, F
Abdul-Ghani, MA
Zhou, LJ
Wang, CH
Li, CL
Holmes, BM
Sloane, LB
Austad, SN
Guo, SD
Musi, N
DeFronzo, RA
Deng, CX
White, MF
Liu, F
Dong, LQ
AF Ryu, Jiyoon
Galan, Amanda K.
Xin, Xiaoban
Dong, Feng
Abdul-Ghani, Muhammad A.
Zhou, Lijun
Wang, Changhua
Li, Cuiling
Holmes, Bekke M.
Sloane, Lauren B.
Austad, Steven N.
Guo, Shaodong
Musi, Nicolas
DeFronzo, Ralph A.
Deng, Chuxia
White, Morris F.
Liu, Feng
Dong, Lily Q.
TI APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of
IRS1/2 to the Insulin Receptor
SO CELL REPORTS
LA English
DT Article
ID ADAPTER PROTEIN APPL1; NITRIC-OXIDE; IN-VIVO; ADIPONECTIN; AKT;
ACTIVATION; OBESITY; KINASE; CELLS; PHOSPHORYLATION
AB Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.
C1 [Ryu, Jiyoon; Galan, Amanda K.; Xin, Xiaoban; Zhou, Lijun; Sloane, Lauren B.; Austad, Steven N.; Dong, Lily Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Dong, Feng; Abdul-Ghani, Muhammad A.; Musi, Nicolas; DeFronzo, Ralph A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Wang, Changhua; Liu, Feng] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Holmes, Bekke M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Austad, Steven N.; Liu, Feng; Dong, Lily Q.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA.
[Li, Cuiling; Deng, Chuxia] NIDDK, Mammalian Genet Sect, GDDB, NIH, Bethesda, MD 20892 USA.
[Guo, Shaodong] Texas A&M Univ, Div Mol Cardiol, Temple, TX 76504 USA.
[White, Morris F.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Endocrinol, Boston, MA 02115 USA.
RP Dong, LQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
EM dongQ@uthscsa.edu
RI deng, chuxia/N-6713-2016
FU Career Development Award from the American Diabetes Association; NIH
[R01 DK080344, R01 DK76902, NIA T32 AG021890]
FX This work was supported in part by a Career Development Award from the
American Diabetes Association (to L.Q.D.) and NIH grants (R01 DK080344
to L.Q.D., R01 DK76902 to F.L., and NIA T32 AG021890 to A.K.G.).
NR 36
TC 24
Z9 25
U1 2
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAY
PY 2014
VL 7
IS 4
BP 1227
EP 1238
DI 10.1016/j.celrep.2014.04.006
PG 12
WC Cell Biology
SC Cell Biology
GA AH9WL
UT WOS:000336495700029
PM 24813896
ER
PT J
AU Hong, SG
Winkler, T
Wu, CF
Guo, V
Pittaluga, S
Nicolae, A
Donahue, RE
Metzger, ME
Price, SD
Uchida, N
Kuznetsov, SA
Kilts, T
Li, L
Robey, PG
Dunbar, CE
AF Hong, So Gun
Winkler, Thomas
Wu, Chuanfeng
Guo, Vicky
Pittaluga, Stefania
Nicolae, Alina
Donahue, Robert E.
Metzger, Mark E.
Price, Sandra D.
Uchida, Naoya
Kuznetsov, Sergei A.
Kilts, Tina
Li, Li
Robey, Pamela G.
Dunbar, Cynthia E.
TI Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a
Nonhuman Primate Model
SO CELL REPORTS
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; MESENCHYMAL STEM; HEMATOPOIETIC-CELLS; STROMAL
CELLS; SELF-RENEWAL; BONE; MOUSE; TRANSPLANTATION; IMMUNOGENICITY;
REGENERATION
AB Induced pluripotent stem cell (iPSC)-based cell therapies have great potential for regenerative medicine but are also potentially associated with tumorigenic risks. Current rodent models are not optimal predictors of efficiency and safety for clinical application. Therefore, we developed a clinically relevant nonhuman primate model to assess the tumorigenic potential and in vivo efficacy of both undifferentiated and differentiated iPSCs in autologous settings without immunosuppression. Undifferentiated autologous iPSCs indeed form mature teratomas in a dose-dependent manner. However, tumor formation is accompanied by an inflammatory reaction. On the other hand, iPSC-derived mesodermal stromal-like cells form new bone in vivo without any evidence of teratoma formation. We therefore show in a large animal model that closely resembles human physiology that undifferentiated autologous iPSCs form teratomas, and that iPSC-derived progenitor cells can give rise to a functional tissue in vivo.
C1 [Hong, So Gun; Winkler, Thomas; Wu, Chuanfeng; Guo, Vicky; Donahue, Robert E.; Metzger, Mark E.; Price, Sandra D.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Pittaluga, Stefania; Nicolae, Alina] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Uchida, Naoya] NHLBI, Mol & Clin Hematol Branch, NIDDK, NIH, Bethesda, MD 20892 USA.
[Kuznetsov, Sergei A.; Kilts, Tina; Li, Li; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dunbarc@nhlbi.nih.gov
RI Wu, Chuanfeng/A-1109-2016
FU Divisions of Intramural Research at the National Heart, Lung and Blood
Institute, the National Institute of Dental and Craniofacial Research;
National Center for Regenerative Medicine at the NIH
FX This research was supported by the Divisions of Intramural Research at
the National Heart, Lung and Blood Institute, the National Institute of
Dental and Craniofacial Research, and the National Center for
Regenerative Medicine at the NIH. We thank the NHLBI Pathology core for
tissue processing and the NHLBI Primate Facility staff for excellent
animal care. The STEMCCA vector was kindly provided by Dr. Gustavo
Mostoslavsky. We also thank Dr. Shoukhrat Mitalipov for providing the
rhesus ESC line (ORMES-22), Dr. Harry L. Malech for sharing the
Cre-GFP-puro plasmid, and Dr. Jichun Chen and Marie Desierto for their
assistance in performing the teratoma assays. We are indebted to Zimmer
for its gift of HA/TCP.
NR 47
TC 27
Z9 27
U1 0
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAY
PY 2014
VL 7
IS 4
BP 1298
EP 1309
DI 10.1016/j.celrep.2014.04.019
PG 12
WC Cell Biology
SC Cell Biology
GA AH9WL
UT WOS:000336495700035
PM 24835994
ER
PT J
AU Rho, J
Ho, N
Prasad, V
AF Rho, Jason
Ho, Nancy
Prasad, Vinay
TI Counterpoint: Were Industry-Sponsored Roflumilast Trials Appropriate? No
SO CHEST
LA English
DT Editorial Material
ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CLINICAL-TRIALS; QUALITY; COPD
C1 [Rho, Jason] Northwestern Univ, Dept Med, Evanston, IL 60208 USA.
[Ho, Nancy] Univ Maryland, Med Ctr, Dept Med, College Pk, MD 20742 USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 24
TC 6
Z9 6
U1 0
U2 1
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD MAY
PY 2014
VL 145
IS 5
BP 939
EP 942
DI 10.1378/chest.14-0114
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AI0IZ
UT WOS:000336532100006
PM 24798831
ER
PT J
AU Rho, J
Ho, N
Prasad, V
AF Rho, Jason
Ho, Nancy
Prasad, Vinay
TI Rebuttal From Dr Rho et al
SO CHEST
LA English
DT Editorial Material
ID ROFLUMILAST
C1 [Rho, Jason] Northwestern Univ, Dept Med, Evanston, IL 60208 USA.
[Ho, Nancy] Univ Maryland, Med Ctr, Dept Med, College Pk, MD 20742 USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr,10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 4
TC 0
Z9 0
U1 1
U2 2
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD MAY
PY 2014
VL 145
IS 5
BP 943
EP 944
DI 10.1378/chest.14-0115
PG 3
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AI0IZ
UT WOS:000336532100008
PM 24798833
ER
PT J
AU Blum, AB
Egorova, NN
Sosunov, EA
Gelijns, AC
DuPree, E
Moskowitz, AJ
Federman, AD
Ascheim, DD
Keyhani, S
AF Blum, Alexander B.
Egorova, Natalia N.
Sosunov, Eugene A.
Gelijns, Annetine C.
DuPree, Erin
Moskowitz, Alan J.
Federman, Alex D.
Ascheim, Deborah D.
Keyhani, Salomeh
TI Impact of Socioeconomic Status Measures on Hospital Profiling in New
York City
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE heart failure; patient readmission; social class
ID CONGESTIVE-HEART-FAILURE; MEDICARE BENEFICIARIES; SOCIAL DETERMINANTS;
30-DAY READMISSION; UNITED-STATES; HEALTH; QUALITY; CARE
AB Background-Current 30-day readmission models used by the Center for Medicare and Medicaid Services for the purpose of hospital-level comparisons lack measures of socioeconomic status (SES). We examined whether the inclusion of an SES measure in 30-day congestive heart failure readmission models changed hospital risk-standardized readmission rates in New York City (NYC) hospitals.
Methods and Results-Using a Centers for Medicare & Medicaid Services (CMS)-like model, we estimated 30-day hospital-level risk-standardized readmission rates by adjusting for age, sex, and comorbid conditions. Next, we examined how hospital risk-standardized readmission rates changed relative to the NYC mean with inclusion of the Agency for Healthcare Research and Quality (AHRQ)-validated SES index score. In a secondary analysis, we examined whether inclusion of the AHRQ SES index score in 30-day readmission models disproportionately impacted the risk-standardized readmission rates of minority-serving hospitals. Higher AHRQ SES scores, indicators of higher SES, were associated with lower odds (0.99) of 30-day readmission (P<0.019). The addition of the AHRQ SES index did not change the model's C statistic (0.63). After adjustment for the AHRQ SES index, 1 hospital changed status from worse than the NYC average to no different than the NYC average. After adjustment for the AHRQ SES index, 1 NYC minority-serving hospital was reclassified from worse to no different than average.
Conclusions-Although patients with higher SES were less likely to be admitted, the impact of SES on readmission was small. In NYC, inclusion of the AHRQ SES score in a CMS-based model did not impact hospital-level profiling based on 30-day readmission.
C1 [Blum, Alexander B.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Blum, Alexander B.; Egorova, Natalia N.; Gelijns, Annetine C.; DuPree, Erin; Moskowitz, Alan J.; Ascheim, Deborah D.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA.
[Moskowitz, Alan J.; Federman, Alex D.] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA.
[Keyhani, Salomeh] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Keyhani, Salomeh] San Francisco VA, San Francisco, CA USA.
RP Blum, AB (reprint author), Evergreen Hlth Inc, 3000 Falls Rd,Suite 1, Baltimore, MD 21211 USA.
EM abb@evergreenmd.org
OI Moskowitz, Alan/0000-0002-4412-9450
FU Health Resources & Administration at Mount Sinai School of Medicine
[T32HP10262]; Veterans Affairs Health Services Research & Development
Career Development award; National Heart, Lung, and Blood Institute
[R01HL116522-01A1]
FX This project was not directly supported by any external grants or funds.
Dr Blum was supported through a National Research Service award from the
Health Resources & Administration at Mount Sinai School of Medicine
(T32HP10262). Dr Keyhani was supported by a Veterans Affairs Health
Services Research & Development Career Development award and a National
Heart, Lung, and Blood Institute award (R01HL116522-01A1).
NR 25
TC 10
Z9 10
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-7705
EI 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD MAY
PY 2014
VL 7
IS 3
BP 391
EP 397
DI 10.1161/CIRCOUTCOMES.113.000520
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI3WQ
UT WOS:000336796300008
PM 24823956
ER
PT J
AU McGaughey, DM
Abaan, HO
Miller, RM
Kropp, PA
Brody, LC
AF McGaughey, David M.
Abaan, Hatice Ozel
Miller, Ryan M.
Kropp, Peter A.
Brody, Lawrence C.
TI Genomics of CpG Methylation in Developing and Developed Zebrafish
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE methylation; epigenetics; zebrafish; development; one-carbon metabolism
ID DNA-METHYLATION; EMBRYONIC-DEVELOPMENT; PLURIPOTENT; PATTERNS; SEQUENCE;
REVEALS; PATHWAY; SYSTEM; CELLS
AB DNA methylation is a dynamic process through which specific chromatin modifications can be stably transmitted from parent to daughter cells. A large body of work has suggested that DNA methylation influences gene expression by silencing gene promoters. However, these conclusions were drawn from data focused mostly on promoter regions. Regarding the entire genome, it is unclear how methylation and gene transcription patterns are related during vertebrate development. To identify the genome-wide distribution of CpG methylation, we created series of high-resolution methylome maps of Danio rerio embryos during development and in mature, differentiated tissues. We found that embryonic and terminal tissues have unique methylation signatures in CpG islands and repetitive sequences. Fully differentiated tissues have increased CpG and LTR methylation and decreased SINE methylation relative to embryonic tissues. Unsupervised clustering analyses reveal that the embryonic and terminal tissues can be classified solely by their methylation patterning. Novel analyses also identify a previously undescribed genome-wide exon methylation signature. We also compared whole genome methylation with genome-wide mRNA expression levels using publicly available RNA-seq datasets. These comparisons revealed previously unrecognized relationships between gene expression, alternative splicing, and exon methylation. Surprisingly, we found that exonic methylation is a better predictor of mRNA expression level than promoter methylation. We also found that transcriptionally skipped exons have significantly less methylation than retained exons. Our integrative analyses reveal highly complex interplay between gene expression, alternative splicing, development, and methylation patterning in zebrafish.
C1 [McGaughey, David M.; Abaan, Hatice Ozel; Miller, Ryan M.; Kropp, Peter A.; Brody, Lawrence C.] NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Brody, LC (reprint author), Bldg 50,Room 5306,50 South Dr, Bethesda, MD 20814 USA.
EM lbrody@mail.nih.gov
FU National Human Genome Research Institute
FX We thank Peter Chines, Narisu Narisu, and Steve Parker for advice
regarding computational approaches, and Laura Elnitski, Francisco
Sanchez Vega, and Steve Parker for reading and commenting on the
manuscript. This work was supported by the Intramural Research Program
of the National Human Genome Research Institute.
NR 45
TC 9
Z9 9
U1 0
U2 22
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD MAY 1
PY 2014
VL 4
IS 5
BP 861
EP 869
DI 10.1534/g3.113.009514
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AH9TA
UT WOS:000336483900011
PM 24657902
ER
PT J
AU Xue, ZY
Ren, MD
Wu, MH
Dai, JB
Rong, YKS
Gao, GJ
AF Xue, Zhaoyu
Ren, Mengda
Wu, Menghua
Dai, Junbiao
Rong, Yikang S.
Gao, Guanjun
TI Efficient Gene Knock-out and Knock-in with Transgenic Cas9 in Drosophila
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE knock-out; knock-in; Cas9; gRNA; Drosophila
ID GENOME; MELANOGASTER; CRISPR/CAS9; STRATEGY; SYSTEM
AB Bacterial Cas9 nuclease induces site-specific DNA breaks using small gRNA as guides. Cas9 has been successfully introduced into Drosophila for genome editing. Here, we improve the versatility of this method by developing a transgenic system that expresses Cas9 in the Drosophila germline. Using this system, we induced inheritable knock-out mutations by injecting only the gRNA into embryos, achieved highly efficient mutagenesis by expressing gRNA from the promoter of a novel non-coding RNA gene, and recovered homologous recombination-based knock-in of a fluorescent marker at a rate of 4.5% by co-injecting gRNA with a circular DNA donor.
C1 [Xue, Zhaoyu; Ren, Mengda; Wu, Menghua; Dai, Junbiao; Gao, Guanjun] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
[Rong, Yikang S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Gao, GJ (reprint author), Tsinghua Univ, Sch Life Sci, Yuanmingyuan Rd 1, Beijing 100084, Peoples R China.
EM gaogu@mail.tsinghua.edu.cn
FU National Natural Science Foundation of China [31171278, 31271542];
National Cancer Institute (NCI)
FX We thank Dr. Hugo J. Bellen and Dr. Johannes Bischoffor for providing
the PiggyBac-9A and pM 3xP3RFP-RFPattP' plasmids. We also thank Wei Wei
for technical assistance with DNA sequencing and PCR analysis. This work
was supported by grants from the National Natural Science Foundation of
China (31171278, 31271542). Research in the laboratory of Y.S.R. is
supported by the intramural program of National Cancer Institute (NCI).
NR 17
TC 15
Z9 18
U1 6
U2 47
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD MAY 1
PY 2014
VL 4
IS 5
BP 925
EP 929
DI 10.1534/g3.114.010496
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA AH9TA
UT WOS:000336483900017
PM 24657904
ER
PT J
AU Allen, JD
Leyva, B
Torres, MI
Ospino, H
Tom, L
Rustan, S
Bartholomew, A
AF Allen, Jennifer D.
Leyva, Bryan
Torres, Maria Idali
Ospino, Hosffman
Tom, Laura
Rustan, Sarah
Bartholomew, Amanda
TI Religious Beliefs and Cancer Screening Behaviors among Catholic Latinos:
Implications for Faith-based Interventions
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Religion; spirituality; Catholicism; Hispanic; Latino; health; cancer
screening; faith-based intervention; health promotion; qualitative
research
ID AFRICAN-AMERICAN-WOMEN; COLORECTAL-CANCER; MEXICAN-AMERICANS;
HEALTH-CARE; EXPLANATORY MODELS; PROSTATE-CANCER; HISPANIC-WOMEN; SOCIAL
TIES; LOW-INCOME; CHURCH
AB Although most U.S. Latinos identify as Catholic, few studies have focused on the influence of this religious tradition on health beliefs among this population. This study explores the role of Catholic religious teachings, practices, and ministry on cancer screening knowledge, attitudes, and behaviors among Latinos. Eight focus groups were conducted with 67 Catholic Latino parishioners in Massachusetts. Qualitative analysis provided evidence of strong reliance on faith, God, and parish leaders for health concerns. Parishes were described as vital sources of health and social support, playing a central role in the community's health. Participants emphasized that their religious beliefs promote positive health behaviors and health care utilization, including the use of cancer screening services. In addition, they expressed willingness to participate in cancer education programs located at their parishes and provided practical recommendations for implementing health programs in parishes. Implications for culturally appropriate health communication and faith-based interventions are discussed.
C1 [Allen, Jennifer D.; Tom, Laura; Bartholomew, Amanda] Dana Farber Canc Inst, Boston, MA 02215 USA.
[Allen, Jennifer D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Leyva, Bryan] NCI, Bethesda, MD 20892 USA.
[Torres, Maria Idali; Rustan, Sarah] Univ Massachusetts, Boston, MA 02125 USA.
[Ospino, Hosffman] Boston Coll, Chestnut Hill, MA 02167 USA.
RP Allen, JD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Phyllis F Cantor Ctr Nursing Res & Patient Care S, 450 Brookline Ave, Boston, MA 02215 USA.
EM Jennifer_allen@dfci.harvard.edu
RI Allen, Jennifer/M-2113-2015
FU NCCDPHP CDC HHS [U48 DP001946, U48DP001946]; NCI NIH HHS [U54 CA156732,
U54CA156732]; NIMHD NIH HHS [R21 MD005976]
NR 109
TC 4
Z9 4
U1 3
U2 18
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
EI 1548-6869
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD MAY
PY 2014
VL 25
IS 2
BP 503
EP 526
PG 24
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AH7VJ
UT WOS:000336343100007
PM 24858865
ER
PT J
AU Nguyen, AB
Belgrave, FZ
AF Nguyen, Anh B.
Belgrave, Faye Z.
TI Suc Khoe La Quan Trong Hon Sac Dep! Health is Better than Beauty! A
Community-based Participatory Research Intervention to Improve Cancer
Screening among Vietnamese Women
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Vietnamese-American; women; breast cancer; cervical cancer; ethnic
identity; collectivism; community-based participatory research
ID CERVICAL-CANCER; AMERICAN WOMEN; ETHNIC-IDENTITY; AFRICAN-AMERICAN;
ASIAN-AMERICANS; PAP-SMEAR; SELF-REPORTS; CHINESE; BREAST; MAMMOGRAPHY
AB This paper examines community-based participatory research (CBPR) intervention approaches in promoting cancer-relevant outcomes for 102 Vietnamese women. Results indicated that the intervention was effective in promoting breast and cervical cancer knowledge, positive attitudes towards breast cancer screening, and breast cancer screening. Collectivism moderated the effect of the intervention on attitudes towards breast cancer screening. The intervention led to more favorable attitudes towards breast cancer screening for women with high levels of collectivism but not for women with low levels. Ethnic identity moderated the effect of the intervention on breast cancer screening: the intervention program led to higher probability of getting a clinical breast exam; however, this effect was more pronounced for women with low ethnic identity than for those with high ethnic identity. The study provides evidence for the effectiveness of culturally-tailored strategies in developing cancer screening interventions for the Vietnamese American population.
C1 [Nguyen, Anh B.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Belgrave, Faye Z.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA.
RP Nguyen, AB (reprint author), 9609 Med Ctr Dr 3E638, Rockville, MD 20850 USA.
EM Anh.Nguyen3@nih.gov
FU NCI NIH HHS [5F31CA136235]
NR 56
TC 3
Z9 3
U1 1
U2 2
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
EI 1548-6869
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD MAY
PY 2014
VL 25
IS 2
BP 605
EP 623
PG 19
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AH7VJ
UT WOS:000336343100013
PM 24858871
ER
PT J
AU Studenski, S
AF Studenski, S.
TI Improving care for community dwelling frail elders through patient and
provider engagement
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Editorial Material
ID COMPREHENSIVE GERIATRIC ASSESSMENT; CONTROLLED-TRIAL; OLDER-ADULTS;
METAANALYSIS; MANAGEMENT; INPATIENT
C1 NIA, Longitudinal Studies Sect, Intramural Program, Baltimore, MD 21225 USA.
RP Studenski, S (reprint author), NIA, Longitudinal Studies Sect, Intramural Program, Baltimore, MD 21225 USA.
EM studenskisa@mail.nih.gov
NR 17
TC 1
Z9 1
U1 1
U2 3
PU SPRINGER FRANCE
PI PARIS
PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE
SN 1279-7707
EI 1760-4788
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PD MAY
PY 2014
VL 18
IS 5
BP 455
EP 456
DI 10.1007/s12603-014-0458-8
PG 2
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA AI1KI
UT WOS:000336609400002
PM 24886727
ER
PT J
AU Coates, TJ
Kulich, M
Celentano, DD
Zelaya, CE
Chariyalertsak, S
Chingono, A
Gray, G
Mbwambo, JKK
Morin, SF
Richter, L
Sweat, M
van Rooyen, H
McGrath, N
Fiamma, A
Laeyendecker, O
Piwowar-Manning, E
Szekeres, G
Donnell, D
Eshleman, SH
AF Coates, Thomas J.
Kulich, Michal
Celentano, David D.
Zelaya, Carla E.
Chariyalertsak, Suwat
Chingono, Alfred
Gray, Glenda
Mbwambo, Jessie K. K.
Morin, Stephen F.
Richter, Linda
Sweat, Michael
van Rooyen, Heidi
McGrath, Nuala
Fiamma, Agnes
Laeyendecker, Oliver
Piwowar-Manning, Estelle
Szekeres, Greg
Donnell, Deborah
Eshleman, Susan H.
CA NIMH Project Accept HPTN 043 Study
TI Effect of community-based voluntary counselling and testing on HIV
incidence and social and behavioural outcomes (NIMH Project Accept; HPTN
043): a cluster-randomised trial
SO LANCET GLOBAL HEALTH
LA English
DT Article
ID SUB-SAHARAN AFRICA; MALE CIRCUMCISION; ANTIRETROVIRAL THERAPY;
PREVENTION; THAILAND; INTERVENTION; TRANSMISSION; STIGMA; RISK; MEN
AB Background Although several interventions have shown reduced HIV incidence in clinical trials, the community-level effect of effective interventions on the epidemic when scaled up is unknown. We investigated whether a multicomponent, multilevel social and behavioural prevention strategy could reduce HIV incidence, increase HIV testing, reduce HIV risk behaviour, and change social and behavioural norms.
Methods For this phase 3 cluster-randomised controlled trial, 34 communities in four sites in Africa and 14 communities in Thailand were randomly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV (intervention group) or standard counselling and testing alone (control group) between January, 2001, and December, 2011. The intervention was designed to make testing more accessible in communities, engage communities through outreach, and provide support services after testing. Randomisation was done by a computer-generated code and was not masked. Data were collected at baseline (n=14 567) and after intervention (n=56 683) by cross-sectional random surveys of community residents aged 18-32 years. The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay. Thailand was excluded from incidence analyses because of low HIV prevalence. This trial is registered at ClinicalTrials.gov, number NCT00203749.
Findings The estimated incidence of HIV in the intervention group was 1.52% versus 1.81% in the control group with an estimated reduction in HIV incidence of 13.9% (relative risk [RR] 0.86, 95% CI 0.73-1.02; p=0.082). HIV incidence was significantly reduced in women older than 24 years (RR=0.70, 0.54-0.90; p=0.0085), but not in other age or sex subgroups. Community-based voluntary counselling and testing increased testing rates by 25% overall (12-39; p=0.0003), by 45% (25-69; p<0.0001) in men and 15% (3-28; p=0.013) in women. No overall effect on sexual risk behaviour was recorded. Social norms regarding HIV testing were improved by 6% (95% CI 3-9) in communities in the intervention group.
Interpretation These results are sufficiently robust, especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour, to recommend the Project Accept approach as an integral part of all interventions (including treatment as prevention) to reduce HIV transmission at the community level. Copyright (C) Coates et al. Open Access article distributed under the terms of CC BY.
C1 [Coates, Thomas J.; Fiamma, Agnes; Szekeres, Greg] Univ Calif Los Angeles, UCLA Ctr World Hlth, Los Angeles, CA 90095 USA.
[Kulich, Michal] Charles Univ Prague, Fac Math & Phys, Prague, Czech Republic.
[Celentano, David D.; Zelaya, Carla E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Chariyalertsak, Suwat] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Chingono, Alfred] Univ Zimbabwe, Coll Hlth Sci, Harare, Zimbabwe.
[Gray, Glenda] Univ Witwatersrand, Chris Hani Baragwanath Hosp, Fac Hlth Sci, Perinatal HIV Res Unit, Soweto, South Africa.
[Mbwambo, Jessie K. K.] Muhimbili Univ Teaching Hosp, Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Morin, Stephen F.] Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA.
[Richter, Linda] Human Sci Res Council, Dalbridge, South Africa.
[Sweat, Michael] Med Univ S Carolina, Family Serv Res Ctr, Charleston, SC 29425 USA.
[van Rooyen, Heidi] Human Sci Res Council, Durban, South Africa.
[McGrath, Nuala] Univ Southampton, Southampton Gen Hosp, Southampton, Hants, England.
[Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Piwowar-Manning, Estelle; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Laeyendecker, Oliver] NIH, Bethesda, MD 20892 USA.
[Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Coates, TJ (reprint author), Univ Calif Los Angeles, UCLA Ctr World Hlth, Los Angeles, CA 90095 USA.
EM tcoates@mednet.ucla.edu
RI Kulich, Michal/B-1483-2013; Maman, Suzanne/A-3802-2016;
OI Kulich, Michal/0000-0002-2812-8968; Laeyendecker,
Oliver/0000-0002-6429-4760; Donnell, Deborah/0000-0002-0587-7480;
Mulawa, Marta/0000-0001-9687-421X
FU US National Institute of Mental Health; Division of AIDS of the US
National Institute of Allergy and Infectious Diseases; Office of AIDS
Research of the US National Institutes of Health
FX US National Institute of Mental Health, the Division of AIDS of the US
National Institute of Allergy and Infectious Diseases, and the Office of
AIDS Research of the US National Institutes of Health.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2214-109X
J9 LANCET GLOB HEALTH
JI Lancet Glob. Health
PD MAY
PY 2014
VL 2
IS 5
BP E267
EP E277
DI 10.1016/S2214-109X(14)70032-4
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AH8YU
UT WOS:000336424900015
PM 25103167
ER
PT J
AU Mehta, HM
Futami, M
Glaubach, T
Lee, DW
Andolina, JR
Yang, Q
Whichard, Z
Quinn, M
Lu, HF
Kao, WM
Przychodzen, B
Sarkar, CA
Minella, A
Maciejewski, JP
Corey, SJ
AF Mehta, H. M.
Futami, M.
Glaubach, T.
Lee, D. W.
Andolina, J. R.
Yang, Q.
Whichard, Z.
Quinn, M.
Lu, H. F.
Kao, W. M.
Przychodzen, B.
Sarkar, C. A.
Minella, A.
Maciejewski, J. P.
Corey, S. J.
TI Alternatively spliced, truncated GCSF receptor promotes leukemogenic
properties and sensitivity to JAK inhibition
SO LEUKEMIA
LA English
DT Article
DE GCSF; GCSFR; myelodysplastic syndromes; acute myeloid leukemia: JAK2
ID COLONY-STIMULATING-FACTOR; SEVERE CONGENITAL NEUTROPENIA; G-CSF
RECEPTOR; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA;
HYPERPROLIFERATIVE RESPONSES; DIFFERENTIATION SIGNALS; MUTATIONS; CELLS;
PROLIFERATION
AB Granulocyte colony-stimulating factor (GCSF) drives the production of myeloid progenitor and precursor cells toward neutrophils via the GCSF receptor (GCSFR, gene name CSF3R). Children with severe congenital neutropenia chronically receive pharmacologic doses of GCSF, and similar to 30% will develop myelodysplasia/ acute myeloid leukemia (AML) associated with GCSFR truncation mutations. In addition to mutations, multiple isoforms of CSF3R have also been reported. We found elevated expression of the alternatively spliced isoform, class IV CSF3R in adult myelodysplastic syndrome/AML patients. Aside from its association with monosomy 7 and higher rates of relapse in pediatric AML patients, little is known about the biology of the class IV isoform. We found developmental regulation of CSF3R isoforms with the class IV expression more representative of a progenitor cell stage. Striking differences were found in phosphoprotein signaling involving Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and cell cycle gene expression. Enhanced proliferation by class IV GCSFR was associated with diminished STAT3 and STAT5 activation, yet showed sensitivity to JAK2 inhibitors. Alterations in the C-terminal domain of the GCSFR result in leukemic properties of enhanced growth, impaired differentiation and resistance to apoptosis, suggesting that they can behave as oncogenic drivers, sensitive to JAK2 inhibition.
C1 [Mehta, H. M.; Futami, M.; Glaubach, T.; Andolina, J. R.; Yang, Q.; Whichard, Z.; Quinn, M.; Lu, H. F.; Corey, S. J.] Northwestern Univ, Feinberg Sch Med,Lurie Childrens Hosp Chicago, Robert H Lurie Comprehens Canc Ctr, Dept Pediat Hematol Oncol & Cell & Mol Biol, Chicago, IL 60611 USA.
[Futami, M.] Univ Tokyo, Inst Med Sci, Div Mol Therapy, Tokyo, Japan.
[Lee, D. W.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Andolina, J. R.] Univ Rochester, Sch Med, Dept Pediat Hematol Oncol, Rochester, NY USA.
[Kao, W. M.; Przychodzen, B.; Maciejewski, J. P.] Cleveland Clin, Taussig Canc Inst Translat Hematol & Oncol Res, Cleveland, OH 44106 USA.
[Sarkar, C. A.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA.
[Minella, A.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Dept Med, Chicago, IL 60611 USA.
RP Corey, SJ (reprint author), Northwestern Univ, Feinberg Sch Med,Lurie Childrens Hosp Chicago, Robert H Lurie Comprehens Canc Ctr, Dept Pediat Hematol Oncol & Cell & Mol Biol, 303 E Super St, Chicago, IL 60611 USA.
EM coreylab@yahoo.com
RI Mehta, Hrishikesh/K-1108-2016;
OI Mehta, Hrishikesh/0000-0001-9140-9765; Minella, Alex/0000-0001-6693-3362
FU NIH Independent Scientist [KO2-HL03794, RO1-CA108992]; JP McCarthy
Foundation; NIH [PO1CA55164, T32CA079447]; Leukemia SPORE [CA100632];
AA/MDS International Foundation
FX We thank Dr Shigekazu Nagata for providing the cDNA for rabbit GHR and
Dr John Crispino for providing the JAK2 inhibitors. Funding to SJC from
NIH Independent Scientist Award KO2-HL03794, RO1-CA108992, JP McCarthy
Foundation, NIH PO1CA55164, Leukemia SPORE CA100632 and AA/MDS
International Foundation; to MF from a New Investigator Award from the
AA/MDS International Foundation; and to TG and JRA from NIH T32CA079447.
NR 45
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U1 1
U2 4
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 MAY
PY 2014
VL 28
IS 5
BP 1041
EP 1051
DI 10.1038/leu.2013.321
PG 11
WC Oncology; Hematology
SC Oncology; Hematology
GA AI2BJ
UT WOS:000336661500008
PM 24170028
ER
PT J
AU Goswami, M
Hensel, N
Smith, BD
Prince, GT
Qin, L
Levitsky, HI
Strickland, SA
Jagasia, M
Savani, BN
Fraser, JW
Sadrzadeh, H
Rajkhowa, T
Ito, S
Jain, NA
Battiwalla, M
Fathi, AT
Levis, MJ
Barrett, AJ
Hourigan, CS
AF Goswami, M.
Hensel, N.
Smith, B. D.
Prince, G. T.
Qin, L.
Levitsky, H. I.
Strickland, S. A.
Jagasia, M.
Savani, B. N.
Fraser, J. W.
Sadrzadeh, H.
Rajkhowa, T.
Ito, S.
Jain, N. A.
Battiwalla, M.
Fathi, A. T.
Levis, M. J.
Barrett, A. J.
Hourigan, C. S.
TI Expression of putative targets of immunotherapy in acute myeloid
leukemia and healthy tissues
SO LEUKEMIA
LA English
DT Letter
ID CANCER-TESTIS ANTIGEN; CELLS; RESPONSES
C1 [Goswami, M.; Hourigan, C. S.] NHLBI, Myeloid Malignancies Sect, NIH, Bethesda, MD 20892 USA.
[Hensel, N.; Ito, S.; Jain, N. A.; Battiwalla, M.; Barrett, A. J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Smith, B. D.; Prince, G. T.; Qin, L.; Levitsky, H. I.; Rajkhowa, T.; Levis, M. J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Levitsky, H. I.] Roche Glycart AG, Canc Immunol Expt Med Pharma Res & Early Dev, Schlieren, Switzerland.
[Strickland, S. A.; Jagasia, M.; Savani, B. N.] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA.
[Fraser, J. W.; Sadrzadeh, H.; Fathi, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Leukaemia, Boston, MA USA.
[Fraser, J. W.; Sadrzadeh, H.; Fathi, A. T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Unit,Div Hematol Oncol, Boston, MA USA.
RP Goswami, M (reprint author), NHLBI, Myeloid Malignancies Sect, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hourigan@nih.gov
RI Hourigan, Christopher/S-2476-2016;
OI Hourigan, Christopher/0000-0002-6189-8067; Strickland,
Stephen/0000-0002-6861-2041
FU Intramural NIH HHS [ZIA HL006163-01]; NCATS NIH HHS [UL1 TR001079]; NCI
NIH HHS [P01 CA015396]
NR 15
TC 14
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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 MAY
PY 2014
VL 28
IS 5
BP 1167
EP 1170
DI 10.1038/leu.2014.14
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA AI2BJ
UT WOS:000336661500030
PM 24472813
ER
PT J
AU Sato, K
Watanabe, R
Hanaoka, H
Harada, T
Nakajima, T
Kim, I
Paik, CH
Choyke, PL
Kobayashi, H
AF Sato, Kazuhide
Watanabe, Rira
Hanaoka, Hirofumi
Harada, Toshiko
Nakajima, Takahito
Kim, Insook
Paik, Chang H.
Choyke, Peter L.
Kobayashi, Hisataka
TI Photoimmunotherapy: Comparative effectiveness of two monoclonal
antibodies targeting the epidermal growth factor receptor
SO MOLECULAR ONCOLOGY
LA English
DT Article
DE Photoimmunotherapy; Epidermal growth factor receptor; Monoclonal
antibody; NIR-fluorescence; Pharmacokinetics
ID SQUAMOUS-CELL CARCINOMA; TUMOR SPHEROIDS; THERAPY; IMMUNOTHERAPY;
RETENTION
AB Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein we compare two commonly available anti-EGFR monoclonal antibodies, cetuximab and panitumumab, for their effectiveness as PIT agents in EGFR positive tumor models. A photosensitizer, IR-700, conjugated to either cetuximab (cet-IR700) or panitumumab (pan-IR700), was evaluated using EGFR-expressing A431 and MDAMB468-luc cells in 2D- and 3D-culture. PIT was conducted with irradiation of NIR light after exposure of the sample or animal to each conjugate. In vivo PIT was performed with fractionated exposure of NIR light after injection of each agent into A431 xenografts or a MDAMB468-luc orthotopic tumor bearing model.
Cet-IR700 and pan-IR700 bound with equal affinity to the cells in 2D-culture and penetrated equally into the 3D-spheroid, resulting in identical PIT cytotoxic effects in vitro. In contrast, in vivo anti-tumor effects of PIT with cet-IR700 were inferior to that of pan-IR700. Assessment of the biodistribution showed lower accumulation into the tumors and more rapid hepatic catabolism of cet-IR700 compared to pan-IR700 Although cet-IR700 and pan-IR700 showed identical in vitro characteristics, pan-IR700 showed better therapeutic tumor responses than cet-IR700 in in vivo mice models due to the prolonged retention of the conjugate in the circulation, suggesting that retention in the circulation is advantageous for tumor responses to PIT. These results suggest that the choice of monoclonal antibody in photosensitizer conjugates may influence the effectiveness of PIT. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies.
C1 [Sato, Kazuhide; Watanabe, Rira; Hanaoka, Hirofumi; Harada, Toshiko; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Kim, Insook] Leidos Biomed Res Inc, Appl Dev Res Directorate, Frederick, MD 20892 USA.
[Paik, Chang H.] NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; JSPS Research Fellowship for Japanese Biomedical and
Behavioral Researchers at NIH
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. K.S. is supported with JSPS Research Fellowship for
Japanese Biomedical and Behavioral Researchers at NIH.
NR 33
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1574-7891
EI 1878-0261
J9 MOL ONCOL
JI Mol. Oncol.
PD MAY
PY 2014
VL 8
IS 3
BP 620
EP 632
DI 10.1016/j.molonc.2014.01.006
PG 13
WC Oncology
SC Oncology
GA AH9OQ
UT WOS:000336472100015
PM 24508062
ER
PT J
AU Grady, PA
Daley, K
AF Grady, Patricia A.
Daley, Karen
TI The 2013 National Nursing Research Roundtable: Advancing the science of
chronic illness self-management
SO NURSING OUTLOOK
LA English
DT Editorial Material
ID OUTCOMES
C1 [Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA.
[Daley, Karen] Amer Nurses Assoc, Silver Spring, MD USA.
RP Grady, PA (reprint author), Care of Gough L, NINR, NIH, 6701 Democracy Blvd,Suite 710, Bethesda, MD 20817 USA.
EM info@ninr.nih.gov
NR 8
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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 0029-6554
EI 1528-3968
J9 NURS OUTLOOK
JI Nurs. Outlook
PD MAY-JUN
PY 2014
VL 62
IS 3
BP 201
EP 203
DI 10.1016/j.outlook.2013.12.001
PG 3
WC Nursing
SC Nursing
GA AH8WL
UT WOS:000336418800007
PM 24602784
ER
PT J
AU Sung, VW
Rogers, RG
Bann, CM
Arya, L
Barber, MD
Lowder, J
Lukacz, ES
Markland, A
Siddiqui, N
Wilmot, A
Meikle, SF
AF Sung, Vivian W.
Rogers, Rebecca G.
Bann, Carla M.
Arya, Lily
Barber, Matthew D.
Lowder, Jerry
Lukacz, Emily S.
Markland, Alayne
Siddiqui, Nazema
Wilmot, Amanda
Meikle, Susan F.
CA Pelvic Floor Disorders Network
TI Symptom Outcomes Important to Women With Anal Incontinence A Conceptual
Framework
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ACCIDENTAL BOWEL LEAKAGE; FECAL INCONTINENCE; URINARY-INCONTINENCE;
HEALTH; PREVALENCE; ADULTS
AB OBJECTIVE: To develop a framework that describes the most important symptom outcomes for anal incontinence treatment from the patient perspective.
METHODS: A conceptual framework was developed by the Pelvic Floor Disorders Network based on four semi-structured focus groups and confirmed in two sets of 10 cognitive interviews including women with anal incontinence. We explored: 1) patient-preferred terminology for describing anal incontinence symptoms; 2) patient definitions of treatment "success"; 3) importance of symptoms and outcomes in the framework; and 4) conceptual gaps (defined as outcomes not previously identified as important). Sessions were conducted according to grounded theory transcribed, coded, and qualitatively and quantitatively analyzed to identify relevant themes. Content and face validity of the framework were further assessed using cognitive interviews.
RESULTS: Thirty-four women participated in focus groups and 20 in cognitive interviews. Overall, 29 (54%) were aged 60 years or older, 42 (78%) were white, and 10 (19%) had a high school degree or less. Two overarching outcome themes were identified: "primary bowel leakage symptoms" and "ancillary bowel symptoms." Subdomains important in primary bowel leakage symptoms included leakage characteristics (symptom frequency, amount of leakage, symptom bother) and conditions when bowel leakage occurs (predictability, awareness, urgency). Subdomains important under ancillary bowel symptoms included emptying disorders (constipation, obstructed defecation, and wiping issues) and discomfort (pain, burning). New outcomes identified included predictability, awareness, wiping issues, and discomfort.
CONCLUSION: Women with anal incontinence desire a wide range of symptom outcomes after treatment. These are captured in our conceptual framework, which can aid clinicians and researchers in assessing anal incontinence.
C1 Brown Univ, Div Urogynecol & Reconstruct Pelv Surg, Dept Obstet & Gynecol, Alpert Med Sch, Providence, RI 02903 USA.
Univ New Mexico, Dept Obstet & Gynecol, Div Urogynecol, Albuquerque, NM 87131 USA.
RTI Int, Program Res Survey Methodol, Res Triangle Pk, NC USA.
Univ Penn, Dept Obstet & Gynecol, Hlth Syst Dept, Div Urogynecol & Pelv Reconstruct Surg, Philadelphia, PA 19104 USA.
Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Ctr Urogynecol & Reconstruct Pelv Surg, Cleveland, OH 44106 USA.
Univ Pittsburgh, Med Ctr, Dept Obstet & Gynecol, Womens Ctr Bladder & Pelv Hlth, Pittsburgh, PA USA.
UC San Diego Hlth Syst, Dept Reprod Med, San Diego, CA USA.
Univ Alabama Birmingham, Dept Med, Birmingham & Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs,Med Ctr,Div Gerontol Geriatr & P, Birmingham, AL 35294 USA.
Duke Univ, Med Ctr, Dept Obstet & Gynecol, Div Urogynecol, Durham, NC 27710 USA.
NICHHD, Bethesda, MD 20892 USA.
RP Sung, VW (reprint author), Brown Univ, Div Urogynecol & Reconstruct Pelv Surg, Women & Infants Hosp, 695 Eddy St, Providence, RI 02903 USA.
EM vsung@wihri.org
FU American Medical Systems; Renew Medical, Inc; Pfizer; Boston Scientific;
MedEdicus; Johnson Johnson; Ethicon; National Institutes of Health
(NIH); Eunice Kennedy Shriver National Institute of Child Health and
Human Development; NIH; National Institute of Diabetes and Digestive and
Kidney Diseases; AUGS
FX Dr. Rogers is a data safety monitoring board chair for the TRANSFORM
trial, sponsored by American Medical Systems. She receives royalties
from UpToDate for her chapter on pelvic organ prolapse. Dr. Lukacz has
been a consultant and received research grants from Renew Medical, Inc,
and Pfizer. She has received a research grant from Boston Scientific,
has been a consultant to AMS, and she has received a stipend for
continuing medical education program development from MedEdicus. She has
also received an educational grant from Johnson & Johnson and Ethicon;
research grant support from the National Institutes of Health (NIH) and
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development; research grant support, travel reimbursement, and honoraria
from the NIH and the National Institute of Diabetes and Digestive and
Kidney Diseases; research funding from AUGS; and medicolegal expert
witness fees from various sources. The other authors did not report any
potential conflicts of interest.
NR 25
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U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
EI 1873-233X
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAY
PY 2014
VL 123
IS 5
BP 1023
EP 1030
DI 10.1097/AOG.0000000000000236
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4BD
UT WOS:000336809400017
PM 24785855
ER
PT J
AU Reddy, UM
Abuhamad, AZ
Levine, D
Saade, GR
AF Reddy, Uma M.
Abuhamad, Alfred Z.
Levine, Deborah
Saade, George R.
CA Fetal Imaging Workshop Invited Par
TI Fetal Imaging Executive Summary of a Joint Eunice Kennedy Shriver
National Institute of Child Health and Human Development, Society for
Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine,
American College of Obstetricians and Gynecologists, American College of
Radiology, Society for Pediatric Radiology, and Society of Radiologists
in Ultrasound Fetal Imaging Workshop
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID CHOROID-PLEXUS CYSTS; AMNIOTIC-FLUID VOLUME; LOW-LYING PLACENTA;
NERVOUS-SYSTEM ABNORMALITIES; INTRACARDIAC ECHOGENIC FOCI; TWIN
TRANSFUSION SYNDROME; BIRTH-WEIGHT DISCORDANCE; LAST MENSTRUAL PERIOD;
INTERNAL OS DISTANCE; ISOLATED SHORT FEMUR
AB Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging (MRI) in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development hosted a workshop to address indications for ultrasound and MRI in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost effectiveness, and to identify research opportunities. This article is the executive summary of the workshop.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Univ Texas Med Branch, Galveston, TX 77555 USA.
RP Reddy, UM (reprint author), 6100 Executive Blvd,Room 4B03F, Bethesda, MD 20892 USA.
EM reddyu@mail.nih.gov
NR 117
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U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAY
PY 2014
VL 123
IS 5
BP 1070
EP 1082
DI 10.1097/AOG.0000000000000245
PG 13
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4BD
UT WOS:000336809400022
PM 24785860
ER
PT J
AU Raju, TNK
Mercer, BM
Burchfield, DJ
Joseph, GF
AF Raju, Tonse N. K.
Mercer, Brian M.
Burchfield, David J.
Joseph, Gerald F., Jr.
TI Periviable Birth Executive Summary of a Joint Workshop by the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, Society for Maternal-Fetal Medicine, American Academy of
Pediatrics, and American College of Obstetricians and Gynecologists
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID EXTREMELY PRETERM INFANTS; EXTREMELY PREMATURE-INFANTS; WEEKS
GESTATIONAL-AGE; WEIGHT INFANTS; ANTENATAL CORTICOSTEROIDS; DELIVERY
ROOM; UNITED-STATES; NEURODEVELOPMENTAL OUTCOMES;
DEVELOPMENTAL-DISABILITY; EMERGENCY CERCLAGE
AB This is an executive summary of a workshop on the management and counseling issues of women anticipated to deliver at a periviable gestation (broadly defined as 20 0/7 through 25 6/7 weeks of gestation), and the treatment options for the newborn. Upon review of the available literature, the workshop panel noted that the rates of neonatal survival and neurodevelopmental disabilities among the survivors vary greatly across the periviable gestations and are significantly influenced by the obstetric and neonatal management practices (eg, antenatal steroid, tocolytic agents, and antibiotic administration; cesarean birth; and local protocols for perinatal care, neonatal resuscitation, and intensive care support). These are, in turn, influenced by the variations in local and regional definitions of limits of viability. Because of the complexities in making difficult management decisions, obstetric and neonatal teams should confer prior to meeting with the family, when feasible. Family counseling should be coordinated with the goal of creating mutual trust, respect, and understanding and should incorporate evidence-based counseling methods. Since clinical circumstances can change rapidly with increasing gestational age, counseling should include discussion of the benefits and risks of various maternal and neonatal interventions at the time of counseling. There should be a plan for follow-up counseling as clinical circumstances evolve. The panel proposed a research agenda and recommended developing educational curricula on the care and counseling of families facing the birth of a periviable infant.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
Soc Maternal Fetal Med, Cleveland, OH USA.
Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA.
Univ Florida, Amer Acad Pediat, Gainesville, FL USA.
Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA.
RP Mercer, BM (reprint author), MetroHlth Med Ctr, Dept Obstet & Gynecol, Suite G267,2500 MetroHlth Dr, Cleveland, OH 44109 USA.
EM bmercer@metrohealth.org
NR 60
TC 27
Z9 29
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD MAY
PY 2014
VL 123
IS 5
BP 1083
EP 1096
DI 10.1097/AOG.0000000000000243
PG 14
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4BD
UT WOS:000336809400023
PM 24785861
ER
PT J
AU Boyce, AM
Tosi, LL
Paul, SM
AF Boyce, Alison M.
Tosi, Laura L.
Paul, Scott M.
TI Bisphosphonate Treatment for Children With Disabling Conditions
SO PM&R
LA English
DT Review
ID X-RAY ABSORPTIOMETRY; BONE-MINERAL DENSITY; SEVERE OSTEOGENESIS
IMPERFECTA; SPINAL-CORD-INJURY; DUCHENNE MUSCULAR-DYSTROPHY; INTRAVENOUS
PAMIDRONATE TREATMENT; QUANTITATIVE COMPUTED-TOMOGRAPHY; SEVERE
CEREBRAL-PALSY; FIBROUS DYSPLASIA; ZOLEDRONIC ACID
AB Fractures are a frequent source of morbidity in children with disabling conditions. The assessment of bone density in this population is challenging, because densitometry is influenced by dynamic forces affecting the growing skeleton and may be further confounded by positioning difficulties and surgical hardware. First-line treatment for pediatric osteoporosis involves conservative measures, including optimizing the management of underlying conditions, maintaining appropriate calcium and vitamin D intake, encouraging weight-bearing physical activity, and monitoring measurements of bone mineral density. Bisphosphonates are a class of medications that increase bone mineral density by inhibiting bone resorption. Although bisphosphonates are commonly prescribed for treatment of adult osteoporosis, their use in pediatric patients is controversial because of the lack of long-term safety and efficacy data.
C1 [Boyce, Alison M.] Childrens Natl Med Ctr, Div Endocrinol & Diabetes, Washington, DC 20010 USA.
[Boyce, Alison M.; Tosi, Laura L.] Childrens Natl Med Ctr, Div Orthopaed & Sports Med, Bone Hlth Program, Washington, DC 20010 USA.
[Paul, Scott M.] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Boyce, AM (reprint author), Childrens Natl Med Ctr, Div Endocrinol & Diabetes, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM aboyce@childrensnational.org
FU Bone Health Program at Children's National Medical Center; Intramural
Research Program at the National Institutes of Health
FX supported by the Bone Health Program at Children's National Medical
Center and the Intramural Research Program at the National Institutes of
Health.
NR 105
TC 6
Z9 6
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
EI 1934-1563
J9 PM&R
JI PM&R
PD MAY
PY 2014
VL 6
IS 5
BP 427
EP 436
DI 10.1016/j.pmrj.2013.10.009
PG 10
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA AI0SR
UT WOS:000336560700009
PM 24368091
ER
PT J
AU Kwon, JY
Romero, R
Mor, G
AF Kwon, Ja-Young
Romero, Roberto
Mor, Gil
TI New Insights into the Relationship between Viral Infection and Pregnancy
Complications
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Complication; infection; pregnancy; virus
ID SPONTANEOUSLY ABORTED PRODUCTS; HUMAN-PAPILLOMAVIRUS INFECTION; INDUCED
PRETERM LABOR; INFLAMMATORY RESPONSE; FETAL INFLAMMATION; PREECLAMPSIA;
TROPHOBLAST; ACTIVATION; DELIVERY; EXPRESSION
AB A recent study by McDonnold and coinvestigators published in Am J Obstet Gynecol reports an association between human papillomavirus (HPV) infection and preeclampsia. The investigation was based on the hypothesis that HPV trophoblast infection results in failed trophoblast invasion, and placental dysfunction and hypoxia. The findings from this study along with previous data addressing the relationship between viral infection and obstetrical complications highlight the relevance of viral infection during pregnancy. A better understanding of mechanisms via which virus leads to pregnancy complications will drive us closer to finding a strategy to prevent adverse outcomes.
C1 [Kwon, Ja-Young; Mor, Gil] Yale Univ, Sch Med, Reprod Immunol Unit, Dept Obstet Gynecol & Reprod Sci, New Haven, CT 06520 USA.
[Kwon, Ja-Young] Yonsei Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
RP Mor, G (reprint author), Yale Univ, Sch Med, Reprod Immunol Unit, Dept Obstet Gynecol & Reprod Sci, 333 Cedar St LSOG 305A, New Haven, CT 06520 USA.
EM gil.mor@yale.edu
FU National Institute of Health, NICDH [P01HD054713, 3N01 HD23342]
FX This study is in part funded by grants from the National Institute of
Health, NICDH P01HD054713 and 3N01 HD23342.
NR 47
TC 9
Z9 10
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD MAY
PY 2014
VL 71
IS 5
BP 387
EP 390
DI 10.1111/aji.12243
PG 4
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AE9AK
UT WOS:000334295600001
PM 24702790
ER
PT J
AU Guo, L
Zheng, Z
Ai, JT
Howatt, DA
Mittelstadt, PR
Thacker, S
Daugherty, A
Ashwell, JD
Remaley, AT
Li, XA
AF Guo, Ling
Zheng, Zhong
Ai, Junting
Howatt, Deborah A.
Mittelstadt, Paul R.
Thacker, Seth
Daugherty, Alan
Ashwell, Jonathan D.
Remaley, Alan T.
Li, Xiang-An
TI Scavenger Receptor BI and High-Density Lipoprotein Regulate Thymocyte
Apoptosis in Sepsis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE apolipoproteins; apoptosis; lipoproteins; scavenger receptors; class B;
sepsis
ID APOLIPOPROTEIN-A-I; SR-BI; GLUCOCORTICOID-RECEPTOR; CHOLESTERYL ESTER;
DYSFUNCTIONAL HDL; SELECTIVE UPTAKE; FAMILIAL HYPERCHOLESTEROLEMIA;
ADRENOCORTICAL-RESPONSE; REDUCES ATHEROSCLEROSIS; POLYMICROBIAL SEPSIS
AB Objective Thymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood.
Approach and Results Septic stress induces glucocorticoids production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI)-null mice, which are completely deficient in inducible glucocorticoids in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture induced profound thymocyte apoptosis in SR-BI+/+ mice, but no thymocyte apoptosis in SR-BI-/- mice because of lack of inducible glucocorticoids. Unexpectedly, supplementation of glucocorticoids only partly restored thymocyte apoptosis in SR-BI-/- mice. We demonstrated that high-density lipoprotein (HDL) is a critical modulator for thymocyte apoptosis. SR-BI+/+ HDL significantly enhanced glucocorticoid-induced thymocyte apoptosis, but SR-BI-/- HDL had no such activity. Further study revealed that SR-BI+/+ HDL modulates glucocorticoid-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI-/- HDL loses such regulatory activity. To understand why SR-BI-/- HDL loses its regulatory activity, we analyzed HDL cholesterol contents. There was 3-fold enrichment of unesterified cholesterol in SR-BI-/- HDL compared with SR-BI+/+ HDL. Normalization of unesterified cholesterol in SR-BI-/- HDL by probucol administration or lecithin cholesteryl acyltransferase expression restored glucocorticoid-induced thymocyte apoptosis, and incorporating unesterified cholesterol into SR-BI+/+ HDL rendered SR-BI+/+ HDL dysfunctional. Using lckCre-GR(fl/fl) mice in which thymocytes lack cecal ligation and puncture-induced thymocyte apoptosis, we showed that lckCre-GR(fl/fl) mice were significantly more susceptible to cecal ligation and puncture-induced septic death than GR(fl/fl) control mice, suggesting that glucocorticoid-induced thymocyte apoptosis is required for protection against sepsis.
Conclusions The findings in this study reveal a novel regulatory mechanism of thymocyte apoptosis in sepsis by SR-BI and HDL.
C1 [Guo, Ling; Zheng, Zhong; Ai, Junting; Li, Xiang-An] Univ Kentucky, Coll Med, Dept Pediat, Lexington, KY 40536 USA.
[Zheng, Zhong; Ai, Junting; Li, Xiang-An] Univ Kentucky, Coll Med, Grad Ctr Nutr Sci, Lexington, KY 40536 USA.
[Howatt, Deborah A.; Daugherty, Alan; Li, Xiang-An] Univ Kentucky, Coll Med, Saha Cardiovasc Res Ctr, Lexington, KY 40536 USA.
[Mittelstadt, Paul R.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
[Thacker, Seth; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Li, XA (reprint author), Univ Kentucky, Coll Med, Dept Pediat, BBSRB B255,741 S Limestone, Lexington, KY 40536 USA.
EM xli2@email.uky.edu
FU National Institute of General Medical Sciences (NIGMS)/National
Institutes of Health (NIH) [R01GM085231, R01GM085231-2S1,
R01GM085231-5S1]; Children's Miracle Network
FX This publication was made possible by grant Nos. R01GM085231,
R01GM085231-2S1, and R01GM085231-5S1 from National Institute of General
Medical Sciences (NIGMS)/National Institutes of Health (NIH). The
content of this article is solely the responsibility of the authors and
do not necessarily represent the official views of the NIGMS or NIH.
This work was also supported by a grant from the Children's Miracle
Network.
NR 52
TC 4
Z9 4
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAY
PY 2014
VL 34
IS 5
BP 966
EP 975
DI 10.1161/ATVBAHA.113.302484
PG 10
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AF0AJ
UT WOS:000334373500007
PM 24603680
ER
PT J
AU Mehta, N
Qamar, A
Qu, L
Qasim, AN
Mehta, NN
Reilly, MP
Rader, DJ
AF Mehta, Nidhi
Qamar, Arman
Qu, Liming
Qasim, Atif N.
Mehta, Nehal N.
Reilly, Muredach P.
Rader, Daniel J.
TI Differential Association of Plasma Angiopoietin-Like Proteins 3 and 4
With Lipid and Metabolic Traits
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE angiopoietins; cholesterol; HDL; cholesterol; LDL; diabetes mellitus;
epidemiology; lipid metabolism; lipids; lipoproteins; triglycerides
ID TRIGLYCERIDE-METABOLISM; ANGPTL4; OVEREXPRESSION; CHOLESTEROL; DISEASE;
RISK; LOCI; HDL
AB Objective Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) are secreted proteins that inhibit lipoprotein lipase in vitro. Genetic variants at the ANGPTL3 and ANGPTL4 gene loci are significantly associated with plasma lipid traits. The aim of this study was to evaluate the association of plasma ANGPTL3 and ANGPTL4 concentrations with lipid and metabolic traits in a large community-based sample.
Approach and Results Plasma ANGPTL3 and ANGPTL4 levels were measured in 1770 subjects using a validated ELISA assay. A Pearson unadjusted correlation analysis and a linear regression analysis adjusting for age, sex, and race were performed. ANGPTL3 levels were significantly positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels (both P<2x10(-5)) but not triglycerides. In contrast, ANGPTL4 levels were significantly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (both P<2x10(-5)) and positively associated with triglycerides (P=0.003). In addition, ANGPTL4, but not ANGPTL3, levels were significantly positively associated with fasting blood glucose and metabolic syndrome.
Conclusions Despite having similar biochemical effects in vitro, plasma ANGPTL3 and ANGPTL4 concentrations have nearly opposite relationships with plasma lipids. ANGPTL4 is strongly negatively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and positively with multiple features of the metabolic syndrome including triglycerides, whereas ANGPTL3 is positively associated with low-density lipoprotein cholesterol and high-density lipoprotein cholesterol and not with metabolic syndrome traits including triglycerides. Although ANGPTL3 and ANGPTL4 both inhibit lipoprotein lipase in vitro and influence lipoprotein metabolism in vivo, the physiology of these related proteins and their effects on lipoproteins is clearly divergent and complex.
C1 [Mehta, Nidhi; Qamar, Arman; Qu, Liming; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Mehta, Nidhi; Qamar, Arman; Qu, Liming; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Qasim, Atif N.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA.
RP Mehta, N (reprint author), Univ Penn, Div Cardiovasc Med, 3400 Civ Ctr Blvd,9 Gates Bldg, Philadelphia, PA 19104 USA.
EM nidhi.mehta@uphs.upenn.edu
FU National Heart, Lung, and Blood Institute [R37 HL055323, RC2 HL101834]
FX This work was supported by grants R37 HL055323 and RC2 HL101834 from the
National Heart, Lung, and Blood Institute.
NR 22
TC 13
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAY
PY 2014
VL 34
IS 5
BP 1057
EP 1063
DI 10.1161/ATVBAHA.113.302802
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AF0AJ
UT WOS:000334373500016
PM 24626437
ER
PT J
AU Huang, J
Huffman, JE
Yamkauchi, M
Trompet, S
Asselbergs, FW
Sabater-Lleal, M
Tregouet, DA
Chen, WM
Smith, NL
Kleber, ME
Shin, SY
Becker, DM
Tang, WH
Dehghan, A
Johnson, AD
Truong, V
Folkersen, L
Yang, Q
Oudot-Mellkah, T
Buckley, BM
Moore, JH
Williams, FMK
Campbell, H
Silbernagel, G
Vitart, V
Rudan, I
Tofler, GH
Navis, GJ
DeStefano, A
Wright, AF
Chen, MH
de Craen, AJM
Worrall, BB
Rudnicka, AR
Rumley, A
Bookman, EB
Psaty, BM
Chen, F
Keene, KL
Franco, OH
Bohm, BO
Uitterlinden, AG
Carter, AM
Jukema, JW
Sattar, N
Bis, JC
Ikram, MA
Sale, MM
McKnight, B
Fornage, M
Ford, I
Taylor, K
Slagboom, PE
McArdle, WL
Hsu, FC
Franco-Cereceda, A
Goodall, AH
Yanek, LR
Furie, KL
Cushman, M
Hofman, A
Witteman, JCM
Folsom, AR
Basu, S
Matijevic, N
van Gilst, WH
Wilson, JF
Westendorp, RGJ
Kathiresan, S
Reilly, MP
Tracy, RP
Polasek, O
Winkelmann, BR
Grant, PJ
Hillege, HL
Cambien, F
Stott, DJ
Lowe, GD
Spector, TD
Meigs, JB
Marz, W
Eriksson, P
Becker, LC
Morange, PE
Soranzo, N
Williams, SM
Hayward, C
van der Harst, P
Hamsten, A
Lowenstein, CJ
Strachan, DP
O'Donnell, CJ
AF Huang, Jie
Huffman, Jennifer E.
Yamkauchi, Munekazu
Trompet, Stella
Asselbergs, Folkert W.
Sabater-Lleal, Maria
Tregouet, David-Alexandre
Chen, Wei-Min
Smith, Nicholas L.
Kleber, Marcus E.
Shin, So-Youn
Becker, Diane M.
Tang, Weihong
Dehghan, Abbas
Johnson, Andrew D.
Vinh Truong
Folkersen, Lasse
Yang, Qiong
Oudot-Mellkah, Tiphaine
Buckley, Brendan M.
Moore, Jason H.
Williams, Frances M. K.
Campbell, Harry
Silbernagel, Guenther
Vitart, Veronique
Rudan, Igor
Tofler, Geoffrey H.
Navis, Gerjan J.
DeStefano, Anita
Wright, Alan F.
Chen, Ming-Huei
de Craen, Anton J. M.
Worrall, Bradford B.
Rudnicka, Alicja R.
Rumley, Ann
Bookman, Ebony B.
Psaty, Bruce M.
Chen, Fang
Keene, Keith L.
Franco, Oscar H.
Boehm, Bernhard O.
Uitterlinden, Andre G.
Carter, Angela M.
Jukema, J. Wouter
Sattar, Naveed
Bis, Joshua C.
Ikram, Mohammad A.
Sale, Michele M.
McKnight, Barbara
Fornage, Myriam
Ford, Ian
Taylor, Kent
Slagboom, P. Eline
McArdle, Wendy L.
Hsu, Fang-Chi
Franco-Cereceda, Anders
Goodall, Alison H.
Yanek, Lisa R.
Furie, Karen L.
Cushman, Mary
Hofman, Albert
Witteman, Jacqueline C. M.
Folsom, Aaron R.
Basu, Saonli
Matijevic, Nena
van Gilst, Wiek H.
Wilson, James F.
Westendorp, Rudi G. J.
Kathiresan, Sekar
Reilly, Muredach P.
Tracy, Russell P.
Polasek, Ozren
Winkelmann, Bernhard R.
Grant, Peter J.
Hillege, Hans L.
Cambien, Francois
Stott, David J.
Lowe, Gordon D.
Spector, Timothy D.
Meigs, James B.
Marz, Winfried
Eriksson, Per
Becker, Lewis C.
Morange, Pierre-Emmanuel
Soranzo, Nicole
Williams, Scott M.
Hayward, Caroline
van der Harst, Pim
Hamsten, Anders
Lowenstein, Charles J.
Strachan, David P.
O'Donnell, Christopher J.
CA CHARGE Consortium Hemostatic
TI Genome-Wide Association Study for Circulating Tissue Plasminogen
Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5
and STX2
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE fibrinolysis; genome-wide association study; hemostasis; meta-analysis;
tissue plasminogen activator
ID VON-WILLEBRAND-FACTOR; CORONARY-ARTERY-DISEASE; ACUTE ISCHEMIC-STROKE;
MYOCARDIAL-INFARCTION; PLASMA-LEVELS; GENETIC-VARIATION; RISK; HEART;
POLYMORPHISMS; INHIBITOR-1
AB Objective Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA.
Approach and Results Fourteen cohort studies with tPA measures (N=26 929) contributed to the meta-analysis. Three loci were significantly associated with circulating tPA levels (P<5.0x10(-8)). The first locus is on 6q24.3, with the lead single nucleotide polymorphism (SNP; rs9399599; P=2.9x10(-14)) within STXBP5. The second locus is on 8p11.21. The lead SNP (rs3136739; P=1.3x10(-9)) is intronic to POLB and <200 kb away from the tPA encoding the gene PLAT. We identified a nonsynonymous SNP (rs2020921) in modest linkage disequilibrium with rs3136739 (r(2)=0.50) within exon 5 of PLAT (P=2.0x10(-8)). The third locus is on 12q24.33, with the lead SNP (rs7301826; P=1.0x10(-9)) within intron 7 of STX2. We further found evidence for the association of lead SNPs in STXBP5 and STX2 with expression levels of the respective transcripts. In in vitro cell studies, silencing STXBP5 decreased the release of tPA from vascular endothelial cells, whereas silencing STX2 increased the tPA release. Through an in silico lookup, we found no associations of the 3 lead SNPs with coronary artery disease or stroke.
Conclusions We identified 3 loci associated with circulating tPA levels, the PLAT region, STXBP5, and STX2. Our functional studies implicate a novel role for STXBP5 and STX2 in regulating tPA release.
C1 [Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Huang, Jie; Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Huffman, Jennifer E.; Vitart, Veronique; Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Yamkauchi, Munekazu; Lowenstein, Charles J.] Univ Rochester, Sch Med & Dent, Dept Med, Aab Cardiovasc Res Inst, Rochester, NY 14642 USA.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RA Leiden, Netherlands.
[Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RA Leiden, Netherlands.
[Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RA Leiden, Netherlands.
[Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.
[Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.
[Asselbergs, Folkert W.] UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England.
[Sabater-Lleal, Maria; Folkersen, Lasse; Slagboom, P. Eline; Hofman, Albert] Karolinska Univ Hosp, Karolinska Inst, Cardiovasc Genet & Genom Grp, Atherosclerosis Res Unit,Dept Med, Stockholm, Sweden.
[Tregouet, David-Alexandre; Vinh Truong; Oudot-Mellkah, Tiphaine; Chen, Fang] Univ Paris 06, INSERM, UMRS 937, Paris, France.
[Tregouet, David-Alexandre; Vinh Truong; Chen, Fang] ICAN Inst Cardiometab & Nutr, Paris, France.
[Chen, Wei-Min; Worrall, Bradford B.; Chen, Fang] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Sale, Michele M.] Univ Virginia, Ctr Publ Hlth Genom, Dept Biochem & Mol Genet, Charlottesville, VA USA.
[Smith, Nicholas L.; Psaty, Bruce M.; McKnight, Barbara] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA USA.
[Smith, Nicholas L.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, VA Off Res & Dev, Seattle, WA USA.
[Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89069 Ulm, Germany.
[Kleber, Marcus E.; McArdle, Wendy L.] Heidelberg Univ, Mannheim Inst Publ Hlth, Med Fac Mannheim, Mannheim, Germany.
[Shin, So-Youn; Sattar, Naveed] Wellcome Trust Sanger Inst, Hinxton, England.
[Shin, So-Youn] Univ Bristol, MRC Ctr CAiTE, Sch Social & Community Med, Bristol, Avon, England.
[McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Dept Social Med, Bristol, Avon, England.
[Becker, Diane M.; Yanek, Lisa R.; Becker, Lewis C.] Johns Hopkins Sch Med, Div Internal Med, Baltimore, MD USA.
[Tang, Weihong; Folsom, Aaron R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Basu, Saonli] Univ Minnesota, Div Biostat, Minneapolis, MN USA.
[Dehghan, Abbas; Franco, Oscar H.; Ikram, Mohammad A.; Goodall, Alison H.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.; Grant, Peter J.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Ikram, Mohammad A.] Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Ikram, Mohammad A.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Dehghan, Abbas; Franco, Oscar H.; Uitterlinden, Andre G.; Slagboom, P. Eline; Goodall, Alison H.; Witteman, Jacqueline C. M.; Westendorp, Rudi G. J.] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Yang, Qiong; DeStefano, Anita; Chen, Ming-Huei] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
[Moore, Jason H.; Williams, Scott M.] Gesiel Sch Med Dartmouth, Dept Genet, Lebanon, NH USA.
[Moore, Jason H.] Gesiel Sch Med Dartmouth, Dept Community & Family Med, Lebanon, NH USA.
[Williams, Frances M. K.; Spector, Timothy D.; Soranzo, Nicole] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Silbernagel, Guenther] Swiss Cardiovasc Ctr, Dept Angiol, Bern, Switzerland.
[Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia.
[Navis, Gerjan J.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[van Gilst, Wiek H.; Hillege, Hans L.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Rudnicka, Alicja R.; Strachan, David P.] St Georges Univ London, Div Populat Hlth Sci & Educ, London, England.
[Rumley, Ann; Stott, David J.; Lowe, Gordon D.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Bookman, Ebony B.] NHGRI, Div Genom Med, Framingham, MA USA.
[Keene, Keith L.] E Carolina Univ, Dept Biol, Greenville, NC USA.
[Keene, Keith L.] E Carolina Univ, Ctr Hlth Dispar Res, Greenville, NC USA.
[Boehm, Bernhard O.] Nanyang Technol Univ, LKC Sch Med, Singapore 639798, Singapore.
[Carter, Angela M.] Univ Leeds, Div Cardiovasc & Diabet Res, Leeds, W Yorkshire, England.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol, Sch Publ Hlth, Houston, TX 77030 USA.
[Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Hemostasis Lab, Houston, TX 77030 USA.
[Taylor, Kent] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Hsu, Fang-Chi] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden.
[Goodall, Alison H.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Keene, Keith L.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Cushman, Mary; Tracy, Russell P.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Kathiresan, Sekar; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Kathiresan, Sekar] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA.
[Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Polasek, Ozren] Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia.
[Winkelmann, Bernhard R.] Cardiol Team Sachsenhausen, Frankfurt, Germany.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Marz, Winfried] Synlab Acad, Mannheim, Germany.
[Marz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria.
[Marz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria.
[Morange, Pierre-Emmanuel] Aix Marseille Univ, INSERM, UMRS 1062, Marseille, France.
RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte St,2nd Floor, Framingham, MA 01702 USA.
EM odonnellc@nhlbi.nih.gov
RI Boehm, Bernhard/F-8750-2015; Wilson, James F/A-5704-2009; Polasek,
Ozren/B-6002-2011; Tregouet, David-Alexandre/E-3961-2016; Rudan,
Igor/I-1467-2012; Hayward, Caroline/M-8818-2016; Johnson,
Andrew/G-6520-2013; Slagboom, P. Eline/R-4790-2016;
OI Soranzo, Nicole/0000-0003-1095-3852; Wilson, James
F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Rudan,
Igor/0000-0001-6993-6884; Hayward, Caroline/0000-0002-9405-9550;
Slagboom, P. Eline/0000-0002-2875-4723; Williams,
Frances/0000-0002-2998-2744; Folkersen, Lasse/0000-0003-0708-9530;
Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X;
Sabater Lleal, Maria/0000-0002-0128-379X
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; Swedish Research Council [12660]; Stockholm County
Council [20090077]; Swedish Heart-Lung Foundation [20090541, 8691];
European Commission (FAD) [Health F2 2008 200647]; Medical Research
Council [G0000934]; Wellcome Trust [068545/Z/02, 076113/B/04/Z];
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institute of Allergy and Infectious Diseases (NIAID);
National Human Genome Research Institute (NHGRI); National Institute of
Child Health and Human Development (NICHD); Juvenile Diabetes Research
Foundation International (JDRF); Juvenile Diabetes Research Foundation
International; Wellcome Trust; National Institute for Health Research
(NIHR); Cambridge Biomedical Research Centre; Wellcome Trust Strategic
Award [079895]; EU [018996, LSHM-CT-2006-037593]; French Ministry of
Research; NHLBI [HHSN268201200036C, N01HC85239, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295,
HL087652, HL105756, N01-HC-35129, N01 HC-15103, N01-HC-75150,
N01-HC-45133]; National Institute of Neurological Disorders and Stroke
NINDS; National Institute on Aging (NIA) [AG023629]; National Center for
Research Resources [UL1RR033176]; National Center for Advancing
Translational Sciences, Clinical & Translational Science Institute
[UL1TR000124]; National Institute of Diabetes and Digestive and Kidney
Disease grant [DK063491]; Medical Research Council UK; Ministry of
Science, Education, and Sport of the Republic of Croatia
[108-10803150302]; EU 6th Framework Programme EUROSPAN project
[LSHG-CT-2006-018947]; NHLBI's Framingham Heart Study [N01-HC-25195];
Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine; Boston
Medical Center; National Institute of Diabetes and Digestive and Kidney
Diseases [K24 DK080140]; GeneSTAR from the National Institutes of Health
(NIH) [1U01 HL072518, R01 HL59684]; Johns Hopkins University School of
Medicine General Clinical Research Center; NIH [M01 RR00052, LM010098,
HL65234, HL67466, RR018787, P01 HL56091, R01 HL074061, R01 HL78635, P01
HL65608]; Knut and Alice Wallenberg Foundation; Swedish Heart-Lung
Foundation; Torsten and Ragnar Sderberg Foundation; Strategic
Cardiovascular Program of Karolinska Institutet; Stockholm County
Council; Foundation for Strategic Research; Marie Curie Intra European
Fellowship within the EU [PIEF-GA-2009-252361]; EU 6th Framework
Programme [LSHG-CT-2006-018947, LSHM-CT-2004-503485]; EU 7th Framework
Programme (Atheroremo) [201668]; EU 7th Framework Programme (RiskyCAD)
[305739]; Program Hospitalier de Recherche Clinique; Fondation pour la
Recherche Medicale; La Region Ile de France (CODDIM); Genomic Network of
the Pierre and Marie Curie University, Paris; Chief Scientist Office of
the Scottish Government; Royal Society; Wellcome Trust Clinical Research
Facility in Edinburgh, United Kingdom; Dutch Kidney Foundation [E033];
Netherlands Heart Foundation [2006B140, 2006T003, 2001 D 032]; EU
project grant GENECURE [2006037697]; NWO VENI [91676170]; Dutch Inter
University Cardiology Institute Netherlands (ICIN); Netherlands
Organization for Health Research and Development (ZonMw) [90700342];
Bristol-Myers Squibb; 7th Framework Programme of the European commission
[223004]; Netherlands Genomics Initiative (Netherlands Consortium for
Healthy Aging) [050-060-810]; Scottish Executive Chief Scientist Office,
Health Services Research Committee [CZG/4/306]; Erasmus Medical Center;
Erasmus University Rotterdam; Netherlands Organization for Scientific
Research (NWO); Netherlands Organization for ZonMw; Research Institute
for Diseases in the Elderly (RIDE); Netherlands Heart Foundation;
Ministry of Education, Culture and Science; Ministry of Health Welfare
and Sports; European Commission; Municipality of Rotterdam; NWO
[175.010.2005.011, 911-03-012, 918-76-619, 916.12.154]; Research
Institute for Diseases in the Elderly [014-93-015]; Netherlands Genomics
Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA)
[050-060-810]; EUR Fellowship; European Community [005268]; ENGAGE
project [HEALTH-F4-2007-201413]; FP-5 GenomEUtwin Project
[QLG2-CT-2002-01254]; Department of Health via the NIHR comprehensive
Biomedical Research Centre; Biotechnology and Biological Sciences
Research Council (BBSRC) project [G20234]; National Eye Institute via an
NIH/Center for Inherited Disease Research (CIDR) genotyping project; Oak
Foundation; American Heart Association (AHA) [EIG 0140210N]; Paul N. Yu
Professorship; AHA [0835446N]; National Human Genome Research Institute
(NHGRI) [U01 HG005160]; NIH; United States Public Health Service [R01
NS34447]; NINDS/NIH; ARIC [U01 HL096917, R01-HL093029]; NIA [AG-023629,
AG-15928, AG-20098, AG-027058, NS17950, AG08122, AG033193]; NINDS; [U01
DK062418]
FX The Atherosclerosis Risk in Communities (ARIC) study is performed as a
collaborative study supported by National Heart, Lung, and Blood
Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Advanced
Study of Aortic Pathology (ASAP) work was supported by the Swedish
Research Council (12660), the Stockholm County Council (20090077), the
Swedish Heart-Lung Foundation (20090541), the European Commission (FAD,
Health F2 2008 200647), and a donation by Fredrik Lundberg. British 1958
Birth Cohort (B58C) was funded by the Medical Research Council (grant
G0000934) and the Wellcome Trust (grant 068545/Z/02;
http://www.b58cgene.sgul.ac.uk/). Genotyping for the B58C-WTCCC subset
was funded by the Wellcome Trust (grant 076113/B/04/Z). The B58C-T1DGC
genotyping used resources provided by the Type 1 Diabetes Genetics
Consortium, a collaborative clinical study sponsored by the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
National Institute of Allergy and Infectious Diseases (NIAID), National
Human Genome Research Institute (NHGRI), National Institute of Child
Health and Human Development (NICHD), and Juvenile Diabetes Research
Foundation International (JDRF), and supported by U01 DK062418.
B58CT1DGC genome-wide association study (GWAS) data were deposited by
the Diabetes and Inflammation Laboratory, Cambridge Institute for
Medical Research (CIMR), University of Cambridge, which is funded by
Juvenile Diabetes Research Foundation International, the Wellcome Trust,
and the National Institute for Health Research (NIHR), Cambridge
Biomedical Research Centre; the CIMR is in receipt of a Wellcome Trust
Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a
contract from the EU 6th Framework Programme (018996) and grants from
the French Ministry of Research. CardioGenics was funded by the EU 6th
Framework Programme (LSHM-CT-2006-037593). The Cardiovascular Health
Study (CHS) was supported by NHLBI contracts HHSN268201200036C,
N01HC85239, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082,
N01HC85083, and N01HC85086, and NHLBI grants HL080295, HL087652,
HL105756 with additional contribution from the National Institute of
Neurological Disorders and Stroke NINDS). Additional support was
provided through AG023629 from the National Institute on Aging (NIA). A
full list of CHS investigators and institutions can be found at -
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping at
Cedars-Sinai Medical Center was supported in part by the National Center
for Research Resources (grant UL1RR033176) and is now at the National
Center for Advancing Translational Sciences, Clinical & 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. The
CROATIAVis study in the Croatian island of Vis was supported through the
grants from the Medical Research Council UK and Ministry of Science,
Education, and Sport of the Republic of Croatia (number 108-10803150302)
and the EU 6th Framework Programme EUROSPAN project (contract no.
LSHG-CT-2006-018947). The Framingham Heart Study was partially supported
by NHLBI's Framingham Heart Study (contract no. N01-HC-25195) and its
contract with Affymetrix, Inc, for genotyping services (contract no.
N02-HL-6-4278).; A portion of this research used the Linux Cluster for
Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment
of the Department of Medicine at Boston University School of Medicine
and Boston Medical Center. Partial investigator support was provided by
National Institute of Diabetes and Digestive and Kidney Diseases (K24
DK080140, to J. B. M). GeneSTAR was supported by grants 1U01 HL072518
and R01 HL59684 from the National Institutes of Health (NIH) and the
Johns Hopkins University School of Medicine General Clinical Research
Center, and the NIH grant M01 RR00052. The Precocious Coronary Artery
Disease Study (PROCARDIS) was supported by the Swedish Research Council
(8691), the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung
Foundation, the Torsten and Ragnar Sderberg Foundation, the Strategic
Cardiovascular Program of Karolinska Institutet and Stockholm County
Council, the Foundation for Strategic Research, and the Stockholm County
Council. M. S.-L. is a recipient of a Marie Curie Intra European
Fellowship within the EU 7th Framework Programme (PIEF-GA-2009-252361).
The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study has
received funding from the EU 6th Framework Programme (integrated project
Bloodomics; grant LSHM-CT-2004-503485) and from the EU 7th Framework
Programme (Atheroremo, grant agreement no. 201668; RiskyCAD, grant
agreement no. 305739). The Marseille Thrombosis Association (MARTHA)
project was supported by a grant from the Program Hospitalier de
Recherche Clinique. T.O.M. was supported by a grant from the Fondation
pour la Recherche Medicale. Statistical analyses in MARTHA benefit from
the C2BIG Computing Centre funded by the Fondation pour la Recherche
Medicale, La Region Ile de France (CODDIM), and the Genomic Network of
the Pierre and Marie Curie University, Paris. The Orkney Complex Disease
Study (ORCADES) was supported by the Chief Scientist Office of the
Scottish Government, the Royal Society, and the EU 6th Framework
Programme EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA
extractions were performed at the Wellcome Trust Clinical Research
Facility in Edinburgh, United Kingdom. Prevention of Renal and Vascular
Endstage Disease (PREVEND) genetics is supported by the Dutch Kidney
Foundation (grant E033), The Netherlands Heart Foundation (grant
2006B140, 2006T003), NIH (grants LM010098, HL65234, HL67466, RR018787),
and the EU project grant GENECURE (FP-6 LSHM CT 2006037697). P.v.d.H. is
supported by the NWO VENI grant 91676170 and the Dutch Inter University
Cardiology Institute Netherlands (ICIN). F.W.A. is supported by a
clinical fellowship from the Netherlands Organization for Health
Research and Development (ZonMw; grant 90700342). Pravastatin in Elderly
Individuals at Risk of Vascular Disease (PROSPER) was supported by an
investigator-initiated grant obtained from Bristol-Myers Squibb. J.W.J.
is an established clinical investigator of the Netherlands Heart
Foundation (grant 2001 D 032). Support for genotyping for the PROSPER/
Pharmacogenetic Study of Statins in the Elderly at Risk (PHASE) study
was provided by the 7th Framework Programme of the European commission
(grant 223004) and by the Netherlands Genomics Initiative (Netherlands
Consortium for Healthy Aging; grant 050-060-810). Measurement of plasma
tissue plasminogen activator was funded by the Scottish Executive Chief
Scientist Office, Health Services Research Committee grant number
CZG/4/306.; The Rotterdam Study is supported by the Erasmus Medical
Center and Erasmus University Rotterdam, the Netherlands Organization
for Scientific Research (NWO), the Netherlands Organization for ZonMw,
the Research Institute for Diseases in the Elderly (RIDE), the
Netherlands Heart Foundation, the Ministry of Education, Culture and
Science, the Ministry of Health Welfare and Sports, the European
Commission, and the Municipality of Rotterdam. Support for genotyping
was provided by NWO (no. 175.010.2005.011, 911-03-012), the Research
Institute for Diseases in the Elderly (014-93-015; RIDE2), the
Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy
Aging (NCHA) project no. 050-060-810. J.C.M.W. is supported by NWO grant
(vici, 918-76-619). A.D. is supported by NWO grant (veni, 916.12.154)
and the EUR Fellowship. The Twins UK study was funded by the Wellcome
Trust, European Community's 6th and 7th Framework Programmes
(FP-6/2005-2008, FP7/2007-2013) LIFE SCIENCES & HEALTH (Ref 005268
Genetic regulation of the end stage clotting process that leads to
thrombotic stroke: the EuroClot Consortium), ENGAGE project
HEALTH-F4-2007-201413 and the FP-5 GenomEUtwin Project
(QLG2-CT-2002-01254). The study also received support from the
Department of Health via the NIHR comprehensive Biomedical Research
Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership
with King's College London. T.D.S. is an NIHR Senior Investigator. The
project also received support from a Biotechnology and Biological
Sciences Research Council (BBSRC) project grant (G20234). The authors
acknowledge the funding and support of the National Eye Institute via an
NIH/Center for Inherited Disease Research (CIDR) genotyping project (PI:
Terri Young). S.-Y.S. is supported by a Post-Doctoral Research
Fellowship from the Oak Foundation. Research at the University of
Rochester was supported by grants from the NIH (P01 HL56091, R01
HL074061, R01 HL78635, P01 HL65608), American Heart Association (AHA;
EIG 0140210N), and the Paul N. Yu Professorship to C.J.L. Supported by
grants from the AHA (0835446N) to M. Y. The GWAS component of the
Vitamin Intervention for Stroke Prevention (VISP) study was supported by
the National Human Genome Research Institute (NHGRI) grant U01 HG005160
(PIs: Michele Sale amd Bradford Worrall), as part of the Genomics and
Randomized Trials Network (GARNET). Genotyping services were provided by
the Johns Hopkins University's CIDR, which is fully funded through a
federal contract from the NIH to the Johns Hopkins University.
Assistance with data cleaning was provided by the GARNET Coordinating
Center (U01 HG005157; PI: Bruce S. Weir). Study recruitment and
collection of data sets for the VISP clinical trial were supported by an
investigator-initiated research grant (R01 NS34447; PI: James Toole)
from the United States Public Health Service, NINDS/NIH. The Cohorts for
Heart and Aging Research in Genome Epidemiology (CHARGE) Consortium
Neurology Working Group was supported by U01 HL096917 and R01-HL093029
for ARIC; by NHLBI contracts N01-HC-35129, N01 HC-15103, N01-HC-75150,
N01-HC-45133, and AG-023629, AG-15928, AG-20098, and AG-027058 from the
NIA, for CHS; and by NINDS and NIA grants NS17950, AG08122, and AG033193
for Framingham Heart Study.
NR 29
TC 14
Z9 14
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAY
PY 2014
VL 34
IS 5
BP 1093
EP 1101
DI 10.1161/ATVBAHA.113.302088
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA AF0AJ
UT WOS:000334373500021
PM 24578379
ER
PT J
AU Singh, BH
Gulley, JL
AF Singh, B. Harpreet
Gulley, James L.
TI Immunotherapy and therapeutic vaccines in prostate cancer: an update on
current strategies and clinical implications
SO ASIAN JOURNAL OF ANDROLOGY
LA English
DT Review
DE androgen deprivation; immunotherapy; prostate cancer; therapeutic cancer
vaccines
ID CYTOTOXIC T-LYMPHOCYTES; DOSE-ESCALATION TRIAL; SIPULEUCEL-T;
TUMOR-CELLS; PHASE-I; METASTATIC MELANOMA; COMBINATION IMMUNOTHERAPY;
CELLULAR IMMUNOTHERAPY; CTLA-4 BLOCKADE; PROSTVAC-VF
AB In recent years, immunotherapy has emerged as a viable and attractive strategy for the treatment of prostate cancer. While there are multiple ways to target the immune system, therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in late-stage clinical trials. The landmark Food and Drug Administration approval of sipuleucel-T for asymptomatic or minimally symptomatic metastatic prostate cancer set the stage for ongoing phase III trials with the cancer vaccine PSA-TRICOM and the immune checkpoint inhibitor ipilimumab. A common feature of these immune-based therapies is the appearance of improved overall survival without short-term changes in disease progression. This class effect appears to be due to modulation of tumor growth rate kinetics, in which the activated immune system exerts constant immunologic pressure that slows net tumor growth. Emerging data suggest that the ideal population for clinical trials of cancer vaccines is patients with lower tumor volume and less aggressive disease. Combination strategies that combine immunotherapy with standard therapies have been shown to augment both immune response and clinical benefit.
C1 [Singh, B. Harpreet; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 81
TC 8
Z9 10
U1 0
U2 7
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 1008-682X
EI 1745-7262
J9 ASIAN J ANDROL
JI Asian J. Androl.
PD MAY
PY 2014
VL 16
IS 3
BP 364
EP 371
DI 10.4103/1008-682X.122585
PG 8
WC Andrology; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA AH4FI
UT WOS:000336082200007
PM 24435055
ER
PT J
AU Li, CD
Chen, DJ
Luo, MY
Ge, M
Zhu, JW
AF Li, Chaodong
Chen, Daijie
Luo, Minyu
Ge, Mei
Zhu, Jianwei
TI Knockdown of ribosomal protein L39 by RNA interference inhibits the
growth of human pancreatic cancer cells in vitro and in vivo
SO BIOTECHNOLOGY JOURNAL
LA English
DT Article
DE Cell growth; Pancreatic cancer; RNA interference; RPL39; Tumor xenograft
ID CASPASE ACTIVATION; K-RAS; EXPRESSION; APOPTOSIS; THERAPY; MICE;
PROGRESSION; SURVIVAL; KRAS
AB Pancreatic cancer remains a major unsolved health problem lacking a potent therapeutic option. Our previous studies showed that the ribosomal protein L39 (RPL39) gene was up-regulated after long-term silencing of oncogenic KRAS in pancreatic cancer PANC-1 cells, which indicated that RPL39 may be important for pancreatic cancer development and survival. In the current study, small interfering RNA (siRNA) targeting of the RPL39 gene was performed to determine the effects of the RPL39 gene on growth of pancreatic cancer PANC-1 and BxPC-3 cells in vitro and in vivo. Results from in vitro experiments showed that knockdown of RPL39 expression with RPL39-siRNA suppressed cell proliferation and specifically enhanced cell apoptosis significantly in both PANC-1 and BxPC-3 cells. The increase of caspase-8 activities and the loss of mitochondrial membrane potential after RPL39 silencing indicated that the RPL39 gene may be involved in caspase-8-related mitochondrial apoptosis. Further, treatment with the RPL39-siRNA inhibited the growth of a human pancreatic cancer xenograft in BALB/c nude mice, accompanied by a decreased expression of RPL39. In the xenograft tumors with injection of RPL39-siRNA, the expressions of Ki-67 and CD31 were significantly down-regulated, and apoptosis was markedly induced. Our findings suggested that siRNA against the RPL39 gene may be of value for gene therapy of pancreatic cancer.
C1 [Li, Chaodong; Ge, Mei; Zhu, Jianwei] Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China.
[Li, Chaodong; Zhu, Jianwei] SJTU, Engn Res Ctr Cell Engn & Therapeut Antibody, Shanghai, Peoples R China.
[Chen, Daijie] China Natl Inst Pharmaceut Ind, Shanghai, Peoples R China.
[Luo, Minyu; Ge, Mei] Shanghai Laiyi Ctr Biopharmaceut R&D, Shanghai, Peoples R China.
[Zhu, Jianwei] Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Zhu, JW (reprint author), Shanghai Jiao Tong Univ, Sch Pharm, 800 Dongchuan Rd, Shanghai 200240, Peoples R China.
EM jianweiz@sjtu.edu.cn
FU National New Drug Research and Development [2010ZX09401-403]
FX We are grateful to Dr. Jianzhong Xi (Peking University, Department of
Biomedical Engineering College of Engineering, Beijing, China) for
assistance with the RNAi experiment and critical reading of the
manuscript. Authors have been supported by National New Drug Research
and Development (Grant 2010ZX09401-403) for this work.
NR 41
TC 1
Z9 1
U1 3
U2 10
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1860-6768
EI 1860-7314
J9 BIOTECHNOL J
JI Biotechnol. J.
PD MAY
PY 2014
VL 9
IS 5
SI SI
BP 652
EP 663
DI 10.1002/biot.201300321
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA AG9WK
UT WOS:000335770500009
PM 24799381
ER
PT J
AU Miller, RK
Darrah, TH
Friedman, A
Li, A
Stodgell, CJ
Landrigan, P
Walker, C
Clark, EB
Dole, N
Thiex, N
Swanson, J
Culhane, J
Szabo, S
Moye, J
AF Miller, R. K.
Darrah, T. H.
Friedman, A.
Li, A.
Stodgell, C. J.
Landrigan, P.
Walker, C.
Clark, E. B.
Dole, N.
Thiex, N.
Swanson, J.
Culhane, J.
Szabo, S.
Moye, J.
TI Environmental Exposures during Pregnancy: US National Children's Study
Formative Research Investigation
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Miller, R. K.; Darrah, T. H.; Friedman, A.; Li, A.; Stodgell, C. J.; Landrigan, P.; Walker, C.; Clark, E. B.; Dole, N.; Thiex, N.; Swanson, J.; Culhane, J.; Szabo, S.; Moye, J.] Natl Childrens Study Placental Consortium, Bethesda, MD USA.
[Miller, R. K.; Friedman, A.; Stodgell, C. J.] Univ Rochester, Rochester, NY USA.
[Darrah, T. H.] Ohio State Univ, Columbus, OH 43210 USA.
[Li, A.] Univ Illinois, Chicago, IL USA.
[Landrigan, P.] Icahn Sch Med, New York, NY USA.
Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Walker, C.] Univ Calif Davis, Davis, CA 95616 USA.
[Swanson, J.] Univ Calif Irvine, Irvine, CA USA.
[Clark, E. B.] Univ Utah, Salt Lake City, UT USA.
[Thiex, N.] S Dakota State Univ, Brookings, SD 57007 USA.
[Dole, N.] Univ N Carolina, Chapel Hill, NC USA.
[Culhane, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Moye, J.] NIH, Bethesda, MD 20892 USA.
OI Li, An/0000-0002-8476-8783
NR 0
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 369
EP 369
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800019
ER
PT J
AU Boyd, WA
Freedman, JH
AF Boyd, W. A.
Freedman, J. H.
TI Development of a C. elegans Assay to Characterize the Effects of
Toxicants on Growth, Reproduction, and Development
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Boyd, W. A.] NIEHS, Div Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Freedman, J. H.] NIEHS, Lab Toxicol & Pharmacol, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 377
EP 377
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800035
ER
PT J
AU Robinson, D
Fenton, S
AF Robinson, D.
Fenton, S.
TI Assessing Early Developmental and Pubertal Effects in CD-1 Mice
Following In Utero Exposure to Bisphenol (BP) Analogs
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Robinson, D.] Univ N Carolina, Chapel Hill, NC USA.
[Robinson, D.; Fenton, S.] NIEHS, NTP Lab Branch, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 387
EP 387
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800052
ER
PT J
AU Rigler, S
Kay, D
Sicko, R
Fan, R
Liu, A
Caggana, M
Browne, M
Druschel, C
Romitti, P
Brody, L
Mills, J
AF Rigler, S.
Kay, D.
Sicko, R.
Fan, R.
Liu, A.
Caggana, M.
Browne, M.
Druschel, C.
Romitti, P.
Brody, L.
Mills, J.
TI Novel Copy Number Variants in a Population-Based Investigation of
Heterotaxy-Associated Congenital Heart Disease
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Rigler, S.] Naval Med Ctr Portsmouth, Portsmouth, VA USA.
[Rigler, S.; Fan, R.; Liu, A.; Mills, J.] NICHD, NIH, Bethesda, MD USA.
[Kay, D.; Sicko, R.; Caggana, M.; Browne, M.; Druschel, C.] New York State Dept Hlth, Albany, NY USA.
[Romitti, P.] Univ Iowa, Iowa City, IA USA.
[Brody, L.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 397
EP 397
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800071
ER
PT J
AU Boghossian, N
Sicko, R
Kay, D
Rigler, S
Yeung, E
Druschel, C
Romitti, P
Browne, M
Fan, R
Liu, A
Brody, L
Mills, J
AF Boghossian, N.
Sicko, R.
Kay, D.
Rigler, S.
Yeung, E.
Druschel, C.
Romitti, P.
Browne, M.
Fan, R.
Liu, A.
Brody, L.
Mills, J.
TI Rare Copy Number Variants in Urinary System and Reproductive Genes
Implicated in Posterior Urethral Valves
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Boghossian, N.; Yeung, E.; Fan, R.; Liu, A.; Mills, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Sicko, R.; Kay, D.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Rigler, S.] Naval Med Ctr Portsmouth, Portsmouth, VA USA.
[Druschel, C.; Browne, M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA.
[Romitti, P.] Univ Iowa, Iowa City, IA USA.
[Brody, L.] NHGRI, Bethesda, MD 20892 USA.
RI Yeung, Edwina/F-5992-2015
OI Yeung, Edwina/0000-0002-3851-2613
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 410
EP 410
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800097
ER
PT J
AU Boghossian, N
Sicko, R
Kay, D
Rigler, S
Yeung, E
Druschel, C
Romitti, P
Browne, M
Fan, R
Liu, A
Brody, L
Mills, J
AF Boghossian, N.
Sicko, R.
Kay, D.
Rigler, S.
Yeung, E.
Druschel, C.
Romitti, P.
Browne, M.
Fan, R.
Liu, A.
Brody, L.
Mills, J.
TI Novel Copy Number Variants in a Population-Based Investigation of Prune
Belly Syndrome
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Boghossian, N.; Yeung, E.; Fan, R.; Liu, A.; Mills, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Sicko, R.; Kay, D.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Rigler, S.] Naval Med Ctr Portsmouth, Portsmouth, VA USA.
[Romitti, P.] Univ Iowa, Iowa City, IA USA.
[Druschel, C.; Browne, M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA.
[Brody, L.] NHGRI, Bethesda, MD 20892 USA.
RI Yeung, Edwina/F-5992-2015
OI Yeung, Edwina/0000-0002-3851-2613
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 425
EP 425
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800125
ER
PT J
AU Hansen, DK
Nakamura, N
Juliar, B
Mcintyre, B
Foster, PMD
Inselman, AL
AF Hansen, D. K.
Nakamura, N.
Juliar, B.
Mcintyre, B.
Foster, P. M. D.
Inselman, A. L.
TI Preliminary Results from Segment I Fertility Study of Oxybenzone in Rats
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Hansen, D. K.; Nakamura, N.; Juliar, B.; Inselman, A. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Mcintyre, B.; Foster, P. M. D.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 429
EP 429
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800134
ER
PT J
AU Inselman, AL
Nakamura, N
Juliar, B
Mcintyre, B
Foster, P
Hansen, DK
AF Inselman, A. L.
Nakamura, N.
Juliar, B.
Mcintyre, B.
Foster, P.
Hansen, D. K.
TI Preliminary Results: Effects of Oxybenzone Exposure on Pre- and
Postnatal Development in Rats
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Inselman, A. L.; Nakamura, N.; Juliar, B.; Hansen, D. K.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Mcintyre, B.; Foster, P.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2014
VL 100
IS 5
SI SI
BP 430
EP 430
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AH7AG
UT WOS:000336283800135
ER
PT J
AU Siebert, M
Sidransky, E
Westbroek, W
AF Siebert, Marina
Sidransky, Ellen
Westbroek, Wendy
TI Glucocerebrosidase is shaking up the synucleinopathies
SO BRAIN
LA English
DT Review
DE glucocerebrosidase; alpha-synuclein; Gaucher disease; Parkinson's
disease; lysosome
ID UNFOLDED PROTEIN RESPONSE; SAPOSIN-C DEFICIENCY; MULTIPLE SYSTEM
ATROPHY; ENDOPLASMIC-RETICULUM STRESS; ACID BETA-GLUCOSIDASE;
NEURONOPATHIC GAUCHER-DISEASE; SPORADIC PARKINSONS-DISEASE;
CHAPERONE-MEDIATED AUTOPHAGY; INHERITED ENZYME DEFICIENCY; LYSOSOMAL
STORAGE DISORDERS
AB Mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase, underlie Gaucher disease and are a risk factor for Parkinson's disease. Siebert et al. review emerging evidence that connects glucocerebrosidase with alpha-synuclein. Therapeutic strategies for Gaucher disease may inform the treatment of Parkinson's disease and other synucleinopathies.The lysosomal enzyme glucocerebrosidase, encoded by the glucocerebrosidase gene, is involved in the breakdown of glucocerebroside into glucose and ceramide. Lysosomal build-up of the substrate glucocerebroside occurs in cells of the reticulo-endothelial system in patients with Gaucher disease, a rare lysosomal storage disorder caused by the recessively inherited deficiency of glucocerebrosidase. Gaucher disease has a broad clinical phenotypic spectrum, divided into non-neuronopathic and neuronopathic forms. Like many monogenic diseases, the correlation between clinical manifestations and molecular genotype is not straightforward. There is now a well-established clinical association between mutations in the glucocerebrosidase gene and the development of more prevalent multifactorial disorders including Parkinson's disease and other synucleinopathies. In this review we discuss recent studies advancing our understanding of the cellular relationship between glucocerebrosidase and alpha-synuclein, the potential impact of established and emerging therapeutics for Gaucher disease for the treatment of the synucleinopathies, and the role of lysosomal pathways in the pathogenesis of these neurodegenerative disorders.
C1 [Siebert, Marina; Sidransky, Ellen; Westbroek, Wendy] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Siebert, Marina] Univ Fed Rio Grande do Sul, Postgrad Program Cellular & Mol Biol, BR-91501970 Porto Alegre, RS, Brazil.
RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35 Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
RI di Ronza, Alberto/H-7674-2016
OI di Ronza, Alberto/0000-0002-9813-5143
FU Intramural Research Programs of the National Human Genome Research
Institute; National Institutes of Health; Brazilian Federal Agency for
Support and Evaluation of Graduate Education CAPES; Fulbright Brazil
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute and the National Institutes of
Health. M. S. received support by the Brazilian Federal Agency for
Support and Evaluation of Graduate Education CAPES and Fulbright Brazil.
NR 221
TC 54
Z9 54
U1 6
U2 25
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD MAY
PY 2014
VL 137
BP 1304
EP 1322
DI 10.1093/brain/awu002
PN 5
PG 19
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH6PK
UT WOS:000336252800012
PM 24531622
ER
PT J
AU Johnson, TV
Martin, KR
Tomarev, SI
AF Johnson, Thomas V.
Martin, Keith R.
Tomarev, Stanislav I.
TI Reply: Platelet-derived growth factor-BB may be involved in mesenchymal
stem cell secretome-induced neuroprotection of retinal ganglion cells
SO BRAIN
LA English
DT Letter
ID PDGF; BRAIN; CHAIN
C1 [Johnson, Thomas V.] Johns Hopkins Sch Med, Baltimore, MD 21205 USA.
[Martin, Keith R.] Univ Cambridge, John van Geest Ctr Brain Repair, Cambridge, England.
[Tomarev, Stanislav I.] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Johnson, TV (reprint author), Johns Hopkins Sch Med, 1830 Monument St,Suite 2-300, Baltimore, MD 21205 USA.
EM tvjohnson@jhmi.edu
RI Johnson, Thomas/C-9351-2011
OI Johnson, Thomas/0000-0002-5372-5457
NR 9
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD MAY
PY 2014
VL 137
BP E277
EP U9
DI 10.1093/brain/awu011
PN 5
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH6PK
UT WOS:000336252800004
PM 24531624
ER
PT J
AU West, ES
Kingsbery, MY
Mintz, EM
Hsu, AP
Holland, SM
Rady, PL
Tyring, SK
Grossman, ME
AF West, E. S.
Kingsbery, M. Y.
Mintz, E. M.
Hsu, A. P.
Holland, S. M.
Rady, P. L.
Tyring, S. K.
Grossman, M. E.
TI Generalized verrucosis in a patient with GATA2 deficiency
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
ID RECALCITRANT CUTANEOUS WARTS; CELL-MEDIATED-IMMUNITY; ACUTE
MYELOID-LEUKEMIA; HUMAN-PAPILLOMAVIRUS; EPIDERMODYSPLASIA-VERRUCIFORMIS;
PRIMARY LYMPHEDEMA; PRIMARY IMMUNODEFICIENCIES; SPORADIC MONOCYTOPENIA;
AUTOSOMAL-DOMINANT; MONOMAC SYNDROME
AB Generalized verrucosis is a characteristic of several genetic and immunodeficiency disorders including epidermodysplasia verruciformis; warts, hypogammaglobulinaemia, infections and myelokathexis (WHIM) syndrome; warts, immunodeficiency, lymphoedema and anogenital dysplasia (WILD) syndrome; severe combined immune deficiency and HIV, among others. In recent years, it has been consistently recognized in patients with GATA2 deficiency, a novel immunodeficiency syndrome characterized by monocytopenia, B-cell and natural killer-cell lymphopenia, and a tendency to develop myeloid leukaemias and disseminated mycobacterial, human papillomavirus (HPV) and opportunistic fungal infections. Mutations in GATA2 cause haploinsufficiency and track in families as an autosomal dominant immunodeficiency. GATA2 is a transcription factor involved in early haematopoietic differentiation and lymphatic and vascular development. We describe a case of generalized verrucosis with HPV type 57 presenting in a young man with GATA2 deficiency. GATA2 deficiency is a novel dominant immunodeficiency that is often recognized later in life and should be considered in the differential diagnosis of patients with generalized verrucosis.
C1 [West, E. S.; Kingsbery, M. Y.; Mintz, E. M.; Grossman, M. E.] Columbia Univ, Dept Dermatol, Med Ctr, New York, NY 10032 USA.
[Hsu, A. P.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Rady, P. L.; Tyring, S. K.] Univ Texas Hlth Sci Ctr Houston, Dept Dermatol, Houston, TX 77030 USA.
RP West, ES (reprint author), Columbia Univ, Dept Dermatol, Med Ctr, 161 Ft Washington Ave 12th Floor, New York, NY 10032 USA.
EM ew2383@columbia.edu
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work is supported in part by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 28
TC 3
Z9 3
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD MAY
PY 2014
VL 170
IS 5
BP 1182
EP 1186
DI 10.1111/bjd.12794
PG 5
WC Dermatology
SC Dermatology
GA AH9BZ
UT WOS:000336436300037
PM 24359037
ER
PT J
AU Bernstein, MB
Garnett, CT
Zhang, HG
Velcich, A
Wattenberg, MM
Gameiro, SR
Kalnicki, S
Hodge, JW
Guha, C
AF Bernstein, Michael B.
Garnett, Charlie T.
Zhang, Huogang
Velcich, Anna
Wattenberg, Max M.
Gameiro, Sofia R.
Kalnicki, Shalom
Hodge, James W.
Guha, Chandan
TI Radiation-Induced Modulation of Costimulatory and Coinhibitory T-Cell
Signaling Molecules on Human Prostate Carcinoma Cells Promotes
Productive Antitumor Immune Interactions
SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
LA English
DT Article
DE immunomodulator; immunotherapy; irradiation; preclinical study; prostate
cancer
ID HUMAN CARCINOEMBRYONIC ANTIGEN; IFN-GAMMA; COMBINED IMMUNOTHERAPY;
CANCER; THERAPY; VACCINE; EXPRESSION; TUMOR; TOLERANCE; PATHWAY
AB We sought to determine if single-dose external beam radiation therapy (EBRT) could modulate the expression signature of T-cell costimulatory and coinhibitory molecules in human prostate cancer (PCa) cell lines in vitro. We investigated the functional impact of irradiated PCa cells with a modulated costimulatory profile on responder T-cell activity. We used three PCa cell lines (DU145, PC3, and LNCaP) and two epithelial cell lines from noncancerous prostate and lung tissue. After 72 hours of EBRT, surface expression of four immunostimulatory molecules (CD70, CD275/ICOSL, CD134L/OX40L, and CD137L/41BBL) and two immunosuppressive markers (CTLA-4/CD152 and PD-L1/CD274) were evaluated by flow cytometry. We evaluated the impact of several radiation doses and the longevity of modulated expression. We examined the functional impact of radiation-induced modulation of cancer cells by cytotoxic T cells (CTL) cytotoxicity and ELISPOT assay for interferon-gamma (IFN-gamma) production. Last, we evaluated whether IFN-gamma-induced PD-L1 expression could be reversed by EBRT. After 10 Gy EBRT, expression of OX40L and 41BBL increased in all three PCa cell lines; expression of CD70 and ICOSL increased in PC3 cells. Conversely, a decrease in PD-L1 expression in DU145 and PC3 cells was detectable up to 144 hours after EBRT. No PD-L1 was detected in LNCaP. Epithelial cells from normal prostate were not modulated by radiation. CTL cytolytic activity and IFN-gamma production were enhanced by interaction with irradiated PCa cells. Finally, EBRT failed to prevent IFN-gamma-induced upregulation of PD-L1. We demonstrate that a single dose of EBRT increased surface expression of costimulatory molecules and decreased the expression of coinhibitory molecules in human PCa cell lines. Changes in irradiated tumor cells led to functional enhancement of T-cell activity, despite EBRT failing to reduce IFN-gamma-induced expression of PD-L1. These data suggest that combining radiotherapy with T-cell stimulating immunotherapy may be an attractive strategy for cancer treatment.
C1 [Bernstein, Michael B.; Zhang, Huogang; Velcich, Anna; Kalnicki, Shalom; Guha, Chandan] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10461 USA.
[Garnett, Charlie T.] Georgia State Univ, Dept Biol, Ctr Inflammat Infect & Immun, Atlanta, GA USA.
[Wattenberg, Max M.; Gameiro, Sofia R.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Guha, C (reprint author), Albert Einstein Coll Med, Montefiore Med Ctr, Dept Radiat Oncol, Mazer Bldg,Room 620,1300 Morris Pk Ave, Bronx, NY 10461 USA.
EM cguhamd@gmail.com
RI Hodge, James/D-5518-2015;
OI Hodge, James/0000-0001-5282-3154; Garnett-Benson,
Charlie/0000-0002-0238-3303
FU NIH [R01 EB009040]; Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX We thank Bonnie L. Casey and Debra Weingarten for editorial assistance
in the preparation of this article. This research was supported by NIH
Grant No. R01 EB009040 and the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 39
TC 22
Z9 23
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1084-9785
EI 1557-8852
J9 CANCER BIOTHER RADIO
JI Cancer Biother. Radiopharm.
PD MAY
PY 2014
VL 29
IS 4
BP 153
EP 161
DI 10.1089/cbr.2013.1578
PG 9
WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy;
Radiology, Nuclear Medicine & Medical Imaging
GA AI0KI
UT WOS:000336535800002
PM 24693958
ER
PT J
AU Ueda, K
Yoshimi, A
Kagoya, Y
Nishikawa, S
Marquez, VE
Nakagawa, M
Kurokawa, M
AF Ueda, Koki
Yoshimi, Akihide
Kagoya, Yuki
Nishikawa, Satoshi
Marquez, Victor E.
Nakagawa, Masahiro
Kurokawa, Mineo
TI Inhibition of histone methyltransferase EZH2 depletes leukemia stem cell
of mixed lineage leukemia fusion leukemia through upregulation of p16
SO CANCER SCIENCE
LA English
DT Article
DE 3-Deazaneplanocin; histones; homeobox proteins; mixed-lineage acute
leukemias; polycomb repressive complex 2
ID CHRONIC MYELOID-LEUKEMIA; MOLECULAR MARKER; POLYCOMB; GENE; BMI-1;
REPRESSION; PROTEINS; METHYLATION; PROGRESSION; EXPRESSION
AB Leukemia stem cells (LSC) are resistant to conventional chemotherapy and persistent LSC after chemotherapy are supposed to be a major cause of relapse. However, information on genetic or epigenetic regulation of stem cell properties is still limited and LSC-targeted drugs have scarcely been identified. Epigenetic regulators are associated with many cellular processes including maintenance of stem cells. Of note are polycomb group proteins, because they potentially control stemness, and can be pharmacologically targeted by a selective inhibitor (DZNep). Therefore, we investigated the therapeutic potential of EZH2 inhibition in mixed lineage leukemia (MLL) fusion leukemia. Intriguingly, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced leukemia initiating cells (LIC) frequency. Expression analysis suggested that p16 upregulation was responsible for LICs reduction. Knockdown of p16 canceled the survival advantage of mice treated with DZNep. Chromatin immunoprecipitation assays demonstrated that EZH2 was highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL and Hoxa9/Meis1 transduced cells but not in E2A/HLF transduced cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells. In summary, our findings show that EZH2 is a potential therapeutic target of MLL fusion leukemia stem cells.
Leukemia stem cells (LSCs) are main cause of relapse or refractoriness to conventional chemotherapy. Although eradicating LSCs are ideal goal for anti-leukemia therapy, drugs targeting LSCs have scarcely been identified. Polycomb group proteins are associated with controlling stemness including activity of cancer stem cells, and can be pharmacologically targeted by a selective inhibitor of H3K27, DZNep. To our surprise, EZH2 inhibition by DZNep or shRNA not only suppressed MLL fusion leukemia proliferation but also reduced LSCs frequency. Dysregulation of p16 is supposed to be responsible for the effect. We also show that EZH2 are highly enriched around the transcription-start-site of p16, together with H3K27 methylation marks in MLL/ENL cells. Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggests that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression. We believe that these findings would help us to develop LICs targeted therapy for MLL fusion leukemia.
C1 [Ueda, Koki; Yoshimi, Akihide; Kagoya, Yuki; Nishikawa, Satoshi; Nakagawa, Masahiro; Kurokawa, Mineo] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo 1138655, Japan.
[Yoshimi, Akihide; Kurokawa, Mineo] Tokyo Univ Hosp, Dept Cell Therapy & Transplantat Med, Tokyo 113, Japan.
[Nishikawa, Satoshi] Kyowa Hakko Kirin, Biol Res Labs, Tokyo, Japan.
[Marquez, Victor E.] NCI Frederick, Biol Chem Lab, Ctr Canc Res, Frederick, MD USA.
RP Kurokawa, M (reprint author), Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan.
EM kurokawa-tky@umin.ac.jp
FU Ministry of Education, Culture, Sports, Science and Technology [KAKENHI
24890045, KAKENHI 24249055]; NIH, National Cancer Institute, Center for
Cancer Research
FX Ministry of Education, Culture, Sports, Science and Technology (KAKENHI
24890045 and 24249055). NIH, National Cancer Institute, Center for
Cancer Research.
NR 46
TC 13
Z9 15
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1349-7006
J9 CANCER SCI
JI Cancer Sci.
PD MAY
PY 2014
VL 105
IS 5
BP 512
EP 519
DI 10.1111/cas.12386
PG 8
WC Oncology
SC Oncology
GA AH0RP
UT WOS:000335828300003
PM 24612037
ER
PT J
AU Qian, WJ
Lai, CC
Kelley, JA
Burke, TR
AF Qian, Wen-Jian
Lai, Christopher C.
Kelley, James A.
Burke, Terrence R., Jr.
TI Design and Synthesis of Fmoc-Thr[PO(OH)(OPOM)] for the Preparation of
Peptide Prodrugs Containing Phosphothreonine in Fully Protected Form
SO CHEMISTRY & BIODIVERSITY
LA English
DT Article
DE Phosphothreonine; Prodrug; Solid-phase synthesis; Peptides; Signal
transduction
ID POLO-BOX DOMAIN; SH2 DOMAIN; SIGNAL-TRANSDUCTION; CELLULAR UPTAKE;
KINASE 1; PHOSPHOPEPTIDES; ALKYLATION; LIGANDS; TARGET; TOOLS
AB The design and efficient synthesis of N-Fmoc-phosphothreonine protected by a mono-(pivaloyloxy)methyl (POM) moiety at its phosphoryl group (Fmoc-Thr[PO(OH)(OPOM)]-OH, 1, is reported. This reagent is suitable for solid-phase syntheses employing acid-labile resins and Fmoc-based protocols. It allows the preparation of phosphothreonine (pThr)-containing peptides bearing bis-POM-phosphoryl protection. The methodology allows the first reported synthesis of pThr-containing polypeptides having bioreversible prodrug protection, and as such it should be useful in a variety of biological applications.
C1 [Qian, Wen-Jian; Lai, Christopher C.; Kelley, James A.; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, POB B, Frederick, MD 21702 USA.
EM burkete@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer
Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the NIH,
Center for Cancer Research, NCI-Frederick and the National Cancer
Institute, National Institutes of Health.
NR 27
TC 1
Z9 1
U1 0
U2 6
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1612-1872
EI 1612-1880
J9 CHEM BIODIVERS
JI Chem. Biodivers.
PD MAY
PY 2014
VL 11
IS 5
BP 784
EP 791
DI 10.1002/cbdv.201300202
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA AH8GY
UT WOS:000336376200010
PM 24827688
ER
PT J
AU Kornides, ML
Nansel, TR
Quick, V
Haynie, DL
Lipsky, LM
Laffel, LMB
Mehta, SN
AF Kornides, M. L.
Nansel, T. R.
Quick, V.
Haynie, D. L.
Lipsky, L. M.
Laffel, L. M. B.
Mehta, S. N.
TI Associations of family meal frequency with family meal habits and meal
preparation characteristics among families of youth with type 1 diabetes
SO CHILD CARE HEALTH AND DEVELOPMENT
LA English
DT Article
DE adolescents; diabetes; family meals; nutrition
ID CHOICE COPING STRATEGIES; DIET QUALITY; EMPLOYED PARENTS; ADOLESCENTS;
PATTERNS; CHILDREN; DINNER; FOOD; VALIDATION; BEHAVIORS
AB BackgroundWhile benefits of family mealtimes, such as improved dietary quality and increased family communication, have been well-documented in the general population, less is known about family meal habits that contribute to more frequent family meals in youth with type 1 diabetes.
MethodsThis cross-sectional study surveyed 282 youth ages 8-18 years with type 1 diabetes and their parents on measures regarding diabetes-related and dietary behaviours. T-tests determined significant differences in youth's diet quality, adherence to diabetes management and glycaemic control between those with and without regular family meals (defined as 5 meals per week). Logistic regression analyses determined unadjusted and adjusted associations of age, socio-demographics, family meal habits, and family meal preparation characteristics with regular family meals.
Results57% of parents reported having regular family meals. Families with regular family meals had significantly better diet quality as measured by the Healthy Eating Index (P < 0.05) and the NRF9.3 (P < 0.01), and adherence to diabetes management (P < 0.001); the difference in glycaemic control approached statistical significance (P = 0.06). Priority placed on, pleasant atmosphere and greater structure around family meals were each associated with regular family meals (P < 0.05). Meals prepared at home were positively associated with regular family meals, while convenience and fast foods were negatively associated (P < 0.05). Families in which at least one parent worked part-time or stayed at home were significantly more likely to have regular family meals than families in which both parents worked full-time (P < 0.05). In the multivariate logistic regression model, greater parental priority given to family mealtimes (P < 0.001) and more home-prepared meals (P < 0.001) predicted occurrence of regular family meals; adjusting for parent work status and other family meal habits.
ConclusionsStrategies for promoting families meals should not only highlight the benefits of family meals, but also facilitate parents' skills for and barriers to home-prepared meals.
C1 [Kornides, M. L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Nansel, T. R.; Quick, V.; Haynie, D. L.; Lipsky, L. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Laffel, L. M. B.; Mehta, S. N.] Harvard Univ, Pediat Adolescent & Young Adult Sect, Genet & Epidemiol Sect, Joslin Diabet Ctr,Med Sch, Boston, MA 02115 USA.
RP Kornides, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM melanie.kornides@mail.harvard.edu
RI Kornides, Melanie/N-5862-2016;
OI Kornides, Melanie/0000-0003-1900-4530; Quick,
Virginia/0000-0002-4338-963X; Nansel, Tonja/0000-0002-8298-7595; Haynie,
Denise/0000-0002-8270-6079; Lipsky, Leah/0000-0003-2645-4388
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Developmen [HHSN267200703434C]; National
Institute of Child Health and Human Development, National Institutes of
Health [T32HD060454]
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.; Melanie Kornides was supported by Training Grant
T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from
the National Institute of Child Health and Human Development, National
Institutes of Health.
NR 25
TC 3
Z9 3
U1 5
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0305-1862
EI 1365-2214
J9 CHILD CARE HLTH DEV
JI Child Care Health Dev.
PD MAY
PY 2014
VL 40
IS 3
BP 405
EP 411
DI 10.1111/cch.12078
PG 7
WC Psychology, Developmental; Pediatrics
SC Psychology; Pediatrics
GA AE8WI
UT WOS:000334283300013
PM 23731337
ER
PT J
AU Aronow, ME
Chew, EY
AF Aronow, Mary E.
Chew, Emily Y.
TI Age-related Eye Disease Study 2: perspectives, recommendations, and
unanswered questions
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE age-related macular degeneration; antioxidant vitamins; lutein; omega-3
fatty acids; zeaxanthin
ID FATTY-ACID INTAKE; MACULAR DEGENERATION; BETA-CAROTENE; VISUAL
IMPAIRMENT; FISH CONSUMPTION; CLINICAL-TRIAL; VITAMIN-C; ZINC;
ASSOCIATIONS; MACULOPATHY
AB Purpose of reviewThis review provides a perspective on the Age-related Eye Disease Study 2 (AREDS2) including a summary of the goals and rationale of the study, major findings, subsequent management recommendations, and questions that remain to be answered.Recent findingsThe primary goal of the AREDS2 was to evaluate the efficacy and safety of lutein plus zeaxanthin and/or omega-3 long-chain polyunsaturated acid supplementation in reducing the risk of developing advanced age-related macular degeneration (AMD). AREDS2 also investigated the effects of omitting -carotene and reducing the concentration of zinc from the original AREDS formulation. Although primary analysis from the AREDS2 did not reveal a benefit of daily supplementation with lutein/zeaxanthin on AMD progression, secondary exploratory analyses suggested that lutein/zeaxanthin were helpful in reducing this risk. Comparison of low-dose to higher-dose zinc showed no significant benefit.SummaryThe overall evidence on the beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than -carotene in AREDS-type supplements. Questions remain regarding the AREDS2 study results such as: whether the findings are generalizable to the population as a whole, what is the long-term safety profile of lutein/zeaxanthin supplementation, should other carotenoids be included in AREDS-type supplements, and at what optimal doses?
C1 [Aronow, Mary E.; Chew, Emily Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU National Eye Institute/National Institutes of Health (NEI/NIH),
Department of Health and Human Services, Bethesda, Maryland
[HHS-N-260-2005-00007-C]; National Eye Institute/National Institutes of
Health (NEI/NIH), Department of Health and Human Services, Bethesda,
Maryland (ADB) [N01-EY-5-0007]
FX The authors have no commercial relationships to disclose. AREDS2 was
supported by the intramural program funds and contracts from the
National Eye Institute/National Institutes of Health (NEI/NIH),
Department of Health and Human Services, Bethesda, Maryland (contract
No. HHS-N-260-2005-00007-C and ADB contract No. N01-EY-5-0007).
NR 31
TC 19
Z9 19
U1 3
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD MAY
PY 2014
VL 25
IS 3
BP 186
EP 190
DI 10.1097/ICU.0000000000000046
PG 5
WC Ophthalmology
SC Ophthalmology
GA AF1GC
UT WOS:000334461400006
PM 24614146
ER
PT J
AU Cobuzzi, JL
Siletti, KA
Hurwitz, ZE
Wetzell, B
Baumann, MH
Riley, AL
AF Cobuzzi, Jennifer L.
Siletti, Kayla A.
Hurwitz, Zachary E.
Wetzell, Bradley
Baumann, Michael H.
Riley, Anthony L.
TI Age Differences in (+/-) 3,4-Methylenedioxymethamphetamine
(MDMA)-Induced Conditioned Taste Aversions and Monoaminergic Levels
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE adolescent; adult; sprague-dawley rats; MDMA; CTA; HPLC; monoamine
ID PLACE PREFERENCE CPP; ADULT-RATS; LONG-TERM; ADOLESCENT RATS; DOPAMINE
RELEASE; FRONTAL-CORTEX; D-AMPHETAMINE; ECSTASY MDMA; STRESS; DRUGS
AB Preclinical work indicates that adolescent rats appear more sensitive to the rewarding effects and less sensitive to the aversive effects of abused drugs. The present investigation utilized the conditioned taste aversion (CTA) design to measure the relative aversive effects of (+/-)3,4-methylenedioxymethamphetamine (MDMA; 0, 1.0, 1.8, or 3.2mg/kg) in adolescent and adult Sprague-Dawley rats. After behavioral testing was complete, monoamine and associated metabolite levels in discrete brain regions were quantified using high-performance liquid chromatography coupled to electrochemical detection (HPLC-ECD) to determine if adolescent animals displayed a different neurochemical profile than did adult animals after being exposed to subcutaneous low doses of MDMA. Adolescent rats displayed less robust MDMA-induced taste aversions than adults during acquisition and on a final two-bottle aversion test. MDMA at these doses had no consistent effect on monoamine levels in either age group, although levels did vary with age. The relative insensitivity of adolescents to MDMA's aversive effects may engender an increased vulnerability to MDMA abuse in this specific population. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 635-646, 2014.
C1 [Cobuzzi, Jennifer L.; Siletti, Kayla A.; Hurwitz, Zachary E.; Wetzell, Bradley; Riley, Anthony L.] Amer Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
[Baumann, Michael H.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA.
RP Cobuzzi, JL (reprint author), Amer Univ, Dept Psychol, Psychopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
EM jen.cobuzzi@american.edu
FU Mellon Foundation; National Institute on Drug Abuse; National Institutes
of Health; Public Health Service; US Department of Health and Human
Services
FX Contract grant sponsor: Mellon Foundation; Grant Sponsor: National
Institute on Drug Abuse; Grant Sponsor: National Institutes of Health;
Grant Sponsor: Public Health Service; Grant Sponsor: US Department of
Health and Human Services.
NR 82
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1630
EI 1098-2302
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD MAY
PY 2014
VL 56
IS 4
BP 635
EP 646
DI 10.1002/dev.21132
PG 12
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA AE1DQ
UT WOS:000333707600004
PM 23775255
ER
PT J
AU Conradt, E
Abar, B
Sheinkopf, S
Lester, B
Lagasse, L
Seifer, R
Shankaran, S
Bada-Ellzey, H
Bauer, C
Whitaker, T
Hinckley, M
Hammond, J
Higgins, R
AF Conradt, Elisabeth
Abar, Beau
Sheinkopf, Stephen
Lester, Barry
Lagasse, Linda
Seifer, Ronald
Shankaran, Seetha
Bada-Ellzey, Henrietta
Bauer, Charles
Whitaker, Toni
Hinckley, Matt
Hammond, Jane
Higgins, Rosemary
TI The Role of Prenatal Substance Exposure and Early Adversity on
Parasympathetic Functioning from 3 to 6 Years of Age
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE allostatic load; prenatal substance exposure; early adversity;
respiratory sinus arrhythmia
ID RESPIRATORY SINUS ARRHYTHMIA; CARDIAC VAGAL TONE; AUTONOMIC
NERVOUS-SYSTEM; CHILD-BEHAVIOR PROBLEMS; STILL-FACE PARADIGM; COCAINE
EXPOSURE; DIFFERENTIAL SUSCEPTIBILITY; PHYSIOLOGICAL REGULATION; STRESS
REACTIVITY; YOUNG-CHILDREN
AB We employed latent growth curve analysis to examine trajectories of respiratory sinus arrhythmia (RSA) from 3 to 6 years among children with varying levels of prenatal substance exposure and early adversity. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,121 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. Overall, there were significant individual differences in the trajectories of RSA reactivity, but not baseline RSA, across development. Greater levels of prenatal substance exposure, and less exposure to early adversity, were associated with increased RSA reactivity at 3 years, but by 6 years, both were associated with greater RSA reactivity. Prenatal substance exposure had an indirect influence through early adversity on growth in RSA reactivity. Results are in support of and contribute to the framework of allostatic load. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1-15, 2013.
C1 [Conradt, Elisabeth; Abar, Beau; Sheinkopf, Stephen; Lester, Barry; Lagasse, Linda; Hinckley, Matt] Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Dept Pediat, Providence, RI 02905 USA.
[Conradt, Elisabeth; Sheinkopf, Stephen; Lester, Barry; Seifer, Ronald] Brown Univ, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48202 USA.
[Bada-Ellzey, Henrietta] Univ Kentucky, Dept Pediat, Lexington, KY 40506 USA.
[Bauer, Charles] Univ Miami, Miller Sch Med, Dept Pediat, Coral Gables, FL 33124 USA.
[Whitaker, Toni] Univ Tennessee, Dept Pediat, Knoxville, TN 37996 USA.
[Hammond, Jane] Res Triangle Inst, Chapel Hill, NC USA.
[Higgins, Rosemary] Natl Inst Hlth, Bethesda, MD USA.
RP Conradt, E (reprint author), Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Dept Pediat, Providence, RI 02905 USA.
EM econradt@wihri.org
OI Seifer, Ronald/0000-0003-4879-2839
FU National Institute of Child Health and Human Development (NICHD)
Neonatal Research Network; National Institute on Drug Abuse (NIDA)
[U10-DA-024117-01, U10-HD-21385, I10-DA-024128-06, U10-HD-2786,
U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397]; NICHD
[N01-HD-2-3159]; National Institute on Drug Abuse [F32DA032175]
FX Contract grant sponsor: National Institute of Child Health and Human
Development (NICHD) Neonatal Research Network; Contract grant sponsor:
National Institute on Drug Abuse (NIDA); Contract grant numbers:
U10-DA-024117-01, U10-HD-21385, I10-DA-024128-06, U10-HD-2786,
U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397; Contract
grant sponsor: NICHD; Contract grant number: N01-HD-2-3159; Contract
grant sponsor: National Institute on Drug Abuse; Contract grant number:
F32DA032175
NR 96
TC 2
Z9 2
U1 6
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1630
EI 1098-2302
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD MAY
PY 2014
VL 56
IS 4
BP 821
EP 835
DI 10.1002/dev.21155
PG 15
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA AE1DQ
UT WOS:000333707600019
PM 24002807
ER
PT J
AU Simpson, EA
Paukner, A
Suomi, SJ
Ferrari, PF
AF Simpson, Elizabeth A.
Paukner, Annika
Suomi, Stephen J.
Ferrari, Pier F.
TI Visual Attention during Neonatal Imitation in Newborn Macaque Monkeys
SO DEVELOPMENTAL PSYCHOBIOLOGY
LA English
DT Article
DE rhesus macaque; infant; visual attention; neonatal imitation; monkey;
newborn; social behavior; communication; facial gestures; mother-infant
interaction; mirror neuron system
ID CHIMPANZEES PAN-TROGLODYTES; FACIAL GESTURES; INFANTS
AB Previous studies suggest that about 50% of rhesus macaque infants engage in neonatal imitation of facial gestures. Here we measured whether individual differences in newborn macaques' (n=49) visual attention may explain why some infants imitate lipsmacking (LPS) and tongue protrusion (TP) gestures. LPS imitators, but not TP imitators, looked more to a human experimenter's face and to a control stimulus compared to nonimitators (p=.017). LPS imitation was equally accurate when infants were looking at faces and when they were looking away (p=.221); TP imitation was more accurate when infants were looking at faces (p=.001). Potentially, less attention is necessary for LPS imitation compared to TP imitation, as LPS is part of macaques' natural communicative repertoire. These findings suggest that facial gestures may differentially engage imitators and nonimitators, and infants' visual attention during neonatal assessments may uncover the conditions that support this skill. (c) 2013 Wiley Periodicals, Inc. Dev Psychobiol 56: 864-870, 2014.
C1 [Simpson, Elizabeth A.; Paukner, Annika; Suomi, Stephen J.; Ferrari, Pier F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Poolesville, MD 20873 USA.
[Simpson, Elizabeth A.; Ferrari, Pier F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
RP Simpson, EA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Poolesville, MD 20873 USA.
EM elizabethannsimpson@gmail.com
OI Simpson, Elizabeth/0000-0003-2715-2533
FU Division of Intramural Research, NICHD; NICHD [P01HD064653]
FX This research was supported by the Division of Intramural Research,
NICHD, and NICHD P01HD064653. We thank Valentina Sclafani, Seth Bower,
Michelle Miller, Judy Songrady, and Angela Ruggiero for help in
collecting the data. Thanks to John Richards and Nathan Fox for data
analysis suggestions.
NR 27
TC 7
Z9 7
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1630
EI 1098-2302
J9 DEV PSYCHOBIOL
JI Dev. Psychobiol.
PD MAY
PY 2014
VL 56
IS 4
BP 864
EP 870
DI 10.1002/dev.21146
PG 7
WC Developmental Biology; Psychology
SC Developmental Biology; Psychology
GA AE1DQ
UT WOS:000333707600023
PM 23794178
ER
PT J
AU Bainbridge, KE
Ramachandran, V
AF Bainbridge, Kathleen E.
Ramachandran, Virginia
TI Hearing Aid Use Among Older U. S. Adults: The National Health and
Nutrition Examination Survey, 2005-2006 and 2009-2010
SO EAR AND HEARING
LA English
DT Article
DE Hearing aids; Hearing loss; Income; Socio-economic factors
ID UNITED-STATES; HELP-SEEKING; IMPAIRMENT; DETERMINANTS; PREVALENCE;
DISABILITY; COMMUNITY; PEOPLE; IMPACT; TRIAL
AB Objectives: The authors estimated the proportion of older adults in the United States who report hearing aid use among those likely to benefit. To more fully understand what factors underlie the low proportion of hearing aid use, the authors examined a variety of socio-demographic correlates as well as measures of health care access and insurance status in relation to hearing aid use among potential hearing aid candidates.
Design: The study makes use of cross-sectional data collected during 2005-2006 and 2009-2010 as part of the National Health and Nutrition Examination Survey. The 1636 adults aged 70 years and older were selected by using a complex sampling design and comprise a nationally representative sample. In addition to self-reported hearing aid use, data on pure-tone thresholds, perceived hearing ability, place for routine health care, time since last hearing test, type of insurance coverage, and socio-demographic characteristics including age, sex, race/ethnicity, family size, and income-to-poverty ratio were collected. The analytical sample consisted of 601 adults who had a better-ear pure-tone average of 35 dB HL at 500, 1000, and 2000 Hz or who reported moderate or worse hearing ability.
Results: One third of the potential hearing aid candidates reported current use of hearing aids. The authors observed a 28 to 66% greater prevalence of hearing aid use among older adults in the upper four fifths of the income-to-poverty distribution compared with those in the bottom one fifth. Compared with people who had their hearing tested 5 to 9 years ago, those with more recent hearing tests were more than two to three times as likely to be a current hearing aid user. No differences were observed by age after adjusting for pure-tone average and no differences were observed by sex after adjusting for perceived hearing ability. No differences were observed by place of routine health care or by type of insurance coverage.
Conclusions: Use of hearing aids is low among older adults who might benefit. Identifying and surmounting barriers to hearing aid use, especially among low-income adults, remains an important objective for hearing health care in the United States.
C1 [Bainbridge, Kathleen E.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Ramachandran, Virginia] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA.
RP Bainbridge, KE (reprint author), Natl Inst Deafness & Other Commun Disorders, 6001 Execut Blvd,Room 8327,MSC 9670, Bethesda, MD 20892 USA.
EM bain-bridgek@mail.nih.gov
FU National Institute on Deafness and Other Communication Disorders
FX The National Institute on Deafness and Other Communication Disorders
provided funding support for The National Health and Nutrition
Examination Survey audiometric data collection via Interagency
Agreements with the National Center for Health Statistics (NCHS),
Centers for Disease Control and Prevention, and the National Institute
for Occupational Safety and Health (NIOSH), Centers for Disease Control
and Prevention.
NR 22
TC 13
Z9 13
U1 1
U2 16
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 MAY-JUN
PY 2014
VL 35
IS 3
BP 289
EP 294
DI 10.1097/01.aud.0000441036.40169.29
PG 6
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA AG7DL
UT WOS:000335578200008
PM 24521924
ER
PT J
AU Coltella, N
Percio, S
Valsecchi, R
Cuttano, R
Guarnerio, J
Ponzoni, M
Pandolfi, PP
Melillo, G
Pattini, L
Bernardi, R
AF Coltella, Nadia
Percio, Stefano
Valsecchi, Roberta
Cuttano, Roberto
Guarnerio, Jlenia
Ponzoni, Maurilio
Pandolfi, Pier Paolo
Melillo, Giovanni
Pattini, Linda
Bernardi, Rosa
TI HIF factors cooperate with PML-RARa to promote acute promyelocytic
leukemia progression and relapse
SO EMBO MOLECULAR MEDICINE
LA English
DT Article
DE acute promyelocytic leukemia; hypoxia-inducible transcription factor;
leukemia-initiating cells; mouse models; PML-RAR
ID TRANS-RETINOIC ACID; CANCER STEM-CELLS; EXPRESSION PROFILES;
HEMATOPOIETIC STEM; MYELOID-LEUKEMIA; GENE-TRANSFER; RECEPTOR;
DIFFERENTIATION; TRANSLOCATION; HIF1-ALPHA
AB Acute promyelocytic leukemia (APL) is epitomized by the chromosomal translocation t(15;17) and the resulting oncogenic fusion protein PML-RAR. Although acting primarily as a transcriptional repressor, PML-RAR can also exert functions of transcriptional co-activation. Here, we find that PML-RAR stimulates transcription driven by HIF factors, which are critical regulators of adaptive responses to hypoxia and stem cell maintenance. Consistently, HIF-related gene signatures are upregulated in leukemic promyelocytes from APL patients compared to normal promyelocytes. Through in vitro and in vivo studies, we find that PML-RAR exploits a number of HIF-1-regulated pro-leukemogenic functions that include cell migration, bone marrow (BM) neo-angiogenesis and self-renewal of APL blasts. Furthermore, HIF-1 levels increase upon treatment of APL cells with all-trans retinoic acid (ATRA). As a consequence, inhibiting HIF-1 in APL mouse models delays leukemia progression and exquisitely synergizes with ATRA to eliminate leukemia-initiating cells (LICs).
C1 [Coltella, Nadia; Valsecchi, Roberta; Cuttano, Roberto; Guarnerio, Jlenia; Bernardi, Rosa] Ist Sci San Raffaele, Div Mol Oncol, Leukemia Unit, I-20132 Milan, Italy.
[Percio, Stefano; Pattini, Linda] Politecn Milan, Dept Elect Informat & Bioengn, I-20133 Milan, Italy.
[Ponzoni, Maurilio] Ist Sci San Raffaele, Pathol Unit, Leukemia Unit, I-20132 Milan, Italy.
[Pandolfi, Pier Paolo] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med & Pathol,Canc Res Inst,Beth Israel Deaco, Boston, MA 02215 USA.
[Melillo, Giovanni] Sci Applicat Int Corp Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Bernardi, R (reprint author), Ist Sci San Raffaele, Div Mol Oncol, Leukemia Unit, I-20132 Milan, Italy.
EM bernardi.rosa@hsr.it
RI bernardi, rosa/B-1650-2013; Cuttano, Roberto/B-5884-2017
OI Cuttano, Roberto/0000-0003-4150-2114
FU Giovanni Armenise-Harvard Foundation; Career Development Award;
Fondazione Cariplo; Italian Association for Cancer Research (AIRC); EU
FX The authors would like to thank all current and previous members of the
laboratory for valuable discussion and support; M. Rocchi for tissue
preparation and immunohistochemistry; M. F. Di Renzo for sharing
reagents and helpful discussion; L. Greenberger, Y. Zhang and Belrose
Pharma Inc. for providing EZN-2968 and EZN-3088; S. Minucci and P. G.
Pelicci for U937-PR9 and U937-MT cell lines; F. Caligaris Cappio and P.
Ghia for insightful discussion. This work was supported by the Giovanni
Armenise-Harvard Foundation with a Career Development Award to R.
Bernardi, and grants by Fondazione Cariplo, Italian Association for
Cancer Research (AIRC, My First AIRC Grant) and the EU (Marie Curie
International Reintegration Grant) to R. Bernardi.
NR 35
TC 12
Z9 12
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1757-4676
EI 1757-4684
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD MAY
PY 2014
VL 6
IS 5
BP 640
EP 650
DI 10.1002/emmm.201303065
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AG4OT
UT WOS:000335400500008
PM 24711541
ER
PT J
AU Hou, YJ
Xiong, B
Zheng, WJ
Duan, X
Cui, XS
Kim, NH
Wang, Q
Xu, YX
Sun, SC
AF Hou, Yan-Jun
Xiong, Bo
Zheng, Wei-Jiang
Duan, Xing
Cui, Xiang-Shun
Nam-Hyung Kim
Wang, Qiang
Xu, Yin-Xue
Sun, Shao-Chen
TI Oocyte Quality in Mice is Affected by a Mycotoxin-Contaminated Diet
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE mycotoxin; oocyte quality; actin; spindle; mitochondria
ID IN-VITRO; GAMMA-TUBULIN; PIG OOCYTES; ZEARALENONE; MATURATION;
FERTILIZATION; DEOXYNIVALENOL; REPRODUCTION; MITOCHONDRIA; EXPOSURE
AB Mycotoxins, such as deoxynivalenol (DON), zearalenone (ZEN), and aflatoxin (AF), are commonly found in many food commodities and may impair the growth and reproductive efficiency of animals and humans. We investigated the effects of a mycotoxin-contaminated diet on mouse oocyte quality. Maize contaminated with DON (3.875 mg/kg), ZEN (1,897 g/kg), and AF (806 g/kg) was incorporated into a mouse diet at three different levels (0, 15, and 30% w/w). After 4 weeks, ovarian and germinal vesicle oocyte indices decreased in mycotoxin-fed mice. Oocytes from these mice exhibited low developmental competence with reduced germinal vesicle breakdown and polar body extrusion rates. Embryo developmental competence also showed a similar pattern, and the majority of embryos could not develop to the morula stage. Actin expression was also reduced in both the oocyte cortex and cytoplasm, which was accompanied by decreased expression of the actin nucleation factors profilin-1 and mDia1. Moreover, a large percentage of oocytes derived from mice that were fed a mycotoxin-contaminated diet exhibited aberrant spindle morphology, a loss of the cortical granule-free domain, and abnormal mitochondrial distributions, which further supported the decreased oocyte quality. Thus, our results demonstrate that mycotoxins are toxic to the mouse reproductive system by affecting oocyte quality. Environ. Mol. Mutagen. 55:354-362, 2014. (c) 2013 Wiley Periodicals, Inc.
C1 [Hou, Yan-Jun; Zheng, Wei-Jiang; Duan, Xing; Xu, Yin-Xue; Sun, Shao-Chen] Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China.
[Xiong, Bo] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Cui, Xiang-Shun; Nam-Hyung Kim] Chungbuk Natl Univ, Dept Anim Sci, Cheongju 361763, South Korea.
[Wang, Qiang] Nanjing Med Univ, State Key Lab Reprod Med, Nanjing 211102, Jiangsu, Peoples R China.
RP Sun, SC (reprint author), Nanjing Agr Univ, Coll Anim Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China.
EM sunsc@njau.edu.cn
FU National Basic Research Program of China [2014CB138503]; National
Natural Science Foundation of China [31301860]; Fundamental Research
Funds for the Central Universities of China [KYRC201202]; BioGreen 21
Program [PJ009594, PJ00956302]
FX Grant sponsor: National Basic Research Program of China; Grant number:
2014CB138503.; Grant sponsor: National Natural Science Foundation of
China; Grant number: 31301860.; Grant sponsor: Fundamental Research
Funds for the Central Universities of China; Grant number: KYRC201202.;
Grant sponsor: BioGreen 21 Program; Grant number: PJ009594 and
PJ00956302.
NR 36
TC 7
Z9 7
U1 0
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
EI 1098-2280
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD MAY
PY 2014
VL 55
IS 4
BP 354
EP 362
DI 10.1002/em.21833
PG 9
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA AE1RA
UT WOS:000333745800006
PM 24288346
ER
PT J
AU Rochitte, CE
George, RT
Chen, MY
Arbab-Zadeh, A
Dewey, M
Miller, JM
Niinuma, H
Yoshioka, K
Kitagawa, K
Nakamori, S
Laham, R
Vavere, AL
Cerci, RJ
Mehra, VC
Nomura, C
Kofoed, KF
Jinzaki, M
Kuribayashi, S
de Roos, A
Laule, M
Tan, SY
Hoe, J
Paul, N
Rybicki, FJ
Brinker, JA
Arai, AE
Cox, C
Clouse, ME
Di Carli, MF
Lima, JAC
AF Rochitte, Carlos E.
George, Richard T.
Chen, Marcus Y.
Arbab-Zadeh, Armin
Dewey, Marc
Miller, Julie M.
Niinuma, Hiroyuki
Yoshioka, Kunihiro
Kitagawa, Kakuya
Nakamori, Shiro
Laham, Roger
Vavere, Andrea L.
Cerci, Rodrigo J.
Mehra, Vishal C.
Nomura, Cesar
Kofoed, Klaus F.
Jinzaki, Masahiro
Kuribayashi, Sachio
de Roos, Albert
Laule, Michael
Tan, Swee Yaw
Hoe, John
Paul, Narinder
Rybicki, Frank J.
Brinker, Jeffery A.
Arai, Andrew E.
Cox, Christopher
Clouse, Melvin E.
Di Carli, Marcelo F.
Lima, Joao A. C.
TI Computed tomography angiography and perfusion to assess coronary artery
stenosis causing perfusion defects by single photon emission computed
tomography: the CORE320 study
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Imaging; Atherosclerosis; Ischemia; Perfusion; Multislice computed
tomography
ID FRACTIONAL FLOW RESERVE; MYOCARDIAL-PERFUSION; CT ANGIOGRAPHY;
DIAGNOSTIC PERFORMANCE; MAGNETIC-RESONANCE; NUCLEAR-CARDIOLOGY;
AMERICAN-SOCIETY; DISEASE; MULTICENTER; STRESS
AB To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT).
We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by a parts per thousand yen50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis a parts per thousand yen50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels.
The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as a parts per thousand yen50 stenosis by ICA causing a perfusion defect by SPECT/MPI.
C1 [George, Richard T.; Arbab-Zadeh, Armin; Miller, Julie M.; Vavere, Andrea L.; Cerci, Rodrigo J.; Mehra, Vishal C.; Brinker, Jeffery A.; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Div Cardiol, Dept Med, Baltimore, MD 21287 USA.
[George, Richard T.; Arbab-Zadeh, Armin; Miller, Julie M.; Vavere, Andrea L.; Cerci, Rodrigo J.; Mehra, Vishal C.; Brinker, Jeffery A.; Lima, Joao A. C.] Sch Med, Baltimore, MD 21287 USA.
[Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Rybicki, Frank J.; Di Carli, Marcelo F.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rochitte, Carlos E.] Univ Sao Paulo, Sch Med, InCor, Inst Heart, Sao Paulo, Brazil.
[Chen, Marcus Y.; Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Dewey, Marc] Charite, Berlin, Germany.
[Niinuma, Hiroyuki; Yoshioka, Kunihiro] Iwate Med Univ, Morioka, Iwate 020, Japan.
[Niinuma, Hiroyuki] St Lukes Int Hosp, Tokyo, Japan.
[Kitagawa, Kakuya; Nakamori, Shiro] Mie Univ Hosp, Tsu, Mie, Japan.
[Laham, Roger; Clouse, Melvin E.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Nomura, Cesar] Albert Einstein Hosp, Sao Paulo, Brazil.
[Kofoed, Klaus F.] Univ Copenhagen, DK-1168 Copenhagen, Denmark.
[Jinzaki, Masahiro; Kuribayashi, Sachio] Keio Univ, Tokyo, Japan.
[de Roos, Albert] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Tan, Swee Yaw] Natl Heart Ctr, Singapore, Singapore.
[Hoe, John] Mt Elizabeth Hosp, Singapore, Singapore.
[Paul, Narinder] Toronto Gen Hosp, Toronto, ON, Canada.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Dept Med, 600 N Wolfe St,Blalock 524, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
OI Dewey, Marc/0000-0002-4402-2733
FU Toshiba Medical Systems Corporation
FX The study sponsor, Toshiba Medical Systems Corporation, was not involved
in any stage of the study design, data acquisition, data analysis, or
manuscript preparation.
NR 33
TC 108
Z9 112
U1 3
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD MAY
PY 2014
VL 35
IS 17
BP 1120
EP +
DI 10.1093/eurheartj/eht488
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH4EO
UT WOS:000336079800009
PM 24255127
ER
PT J
AU Haring, R
Friedrich, N
Volzke, H
Vasan, RS
Felix, SB
Dorr, M
Schwabedissen, HEMZ
Nauck, M
Wallaschofski, H
AF Haring, Robin
Friedrich, Nele
Voelzke, Henry
Vasan, Ramachandran S.
Felix, Stephan B.
Doerr, Marcus
Schwabedissen, Henriette E. Meyer Zu
Nauck, Matthias
Wallaschofski, Henri
TI Positive association of serum prolactin concentrations with all-cause
and cardiovascular mortality
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Prolactin; Mortality; Cardiovascular disease; Population-based cohort
ID N-TERMINAL FRAGMENTS; POSTMENOPAUSAL WOMEN; TESTOSTERONE LEVELS; RISK;
DISEASE; GROWTH; POMERANIA; RECEPTOR; HEALTH; HEART
AB Aims Increased serum prolactin (PRL) concentrations have been associated with adverse cardiovascular risk profiles, but the relation between PRL and mortality risk is unknown.
Methods and results We evaluated 3929 individuals (1946 men and 1983 women) aged 20-81 (mean 50.3 years) from the population-based Study of Health in Pomerania (SHIP). Associations of continuous [per standard deviation (SD) increase] and categorized (sex-specific tertiles) serum PRL concentrations with all-cause and cause-specific mortality were analysed separately for men and women by age- and multivariable-adjusted Cox regression models. During a median follow-up period of 10.1 years (38 231 person-years), 419 deaths (10.7%), 132 cardiovascular deaths (3.4%), and 152 cancer deaths (3.9%) were observed. After multivariable adjustment, we observed a positive association of PRL with all-cause mortality in men and women [hazard ratio (HR) per SD increase: 1.17, 95% confidence interval (CI): 1.07-1.29 and HR: 1.22, 95% CI: 1.03-1.46, respectively]. Similarly, individuals with PRL concentrations in the highest tertile (when compared with lowest PRL tertile) experienced the highest mortality risk (men: HR, 1.75; 95% CI, 1.32-2.32; women: HR, 1.66; 95% CI, 1.08-2.56), with a significant trend across PRL tertiles (P for trend <0.05). Cause-specific mortality analyses yielded similar associations for cardiovascular death in both sexes, but for cancer death only in men.
Conclusion This is the first study to report an independent positive association of PRL concentrations with all-cause and cardiovascular mortality. Further studies are required to confirm our findings and to elucidate the potential role of PRL as a useful biomarker of cardiovascular risk and mortality assessment.
C1 [Haring, Robin; Friedrich, Nele; Nauck, Matthias; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
[Voelzke, Henry] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Felix, Stephan B.; Doerr, Marcus] Univ Med Greifswald, Dept Cardiol, D-17475 Greifswald, Germany.
[Schwabedissen, Henriette E. Meyer Zu] Univ Med Greifswald, Inst Pharmacol, D-17475 Greifswald, Germany.
RP Haring, R (reprint author), Univ Med Greifswald, Inst Clin Chem & Lab Med, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.
EM robin.haring@uni-greifswald.de
OI Ramachandran, Vasan/0000-0001-7357-5970
FU Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103,
01ZZ0403]; Ministry of Cultural Affairs as well as the Social Ministry
of the Federal State of Mecklenburg, West Pomerania; Ministry of
Cultural Affairs of the Federal State of Mecklenburg-West Pomerania
[03IS2061A]; Federal Ministry of Education and Research and the Ministry
of Cultural Affairs of the Federal State of Mecklenburg, West Pomerania,
Germany; Federal Ministry of Education and Research; German Centre for
Cardiovascular Research (GCCR) - Federal Ministry of Education and
Research; Ministry of Cultural Affairs of the Federal State of
Mecklenburg, West Pomerania, Germany
FX Study of Health in Pomerania is part of the Community Medicine Research
net of the University of Greifswald, Germany, which is funded by the
Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, and
01ZZ0403), the Ministry of Cultural Affairs as well as the Social
Ministry of the Federal State of Mecklenburg, West Pomerania. The GANI_
MED consortium is funded by the Federal Ministry of Education and
Research and the Ministry of Cultural Affairs of the Federal State of
Mecklenburg-West Pomerania (03IS2061A). This study was carried out in
collaboration with the German Centre for Cardiovascular Research (GCCR)
which is funded by the Federal Ministry of Education and Research and
the Ministry of Cultural Affairs of the Federal State of Mecklenburg,
West Pomerania, Germany.
NR 48
TC 12
Z9 13
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD MAY
PY 2014
VL 35
IS 18
BP 1215
EP U55
DI 10.1093/eurheartj/ehs233
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH9RT
UT WOS:000336480300015
PM 22843444
ER
PT J
AU Rosso, AL
Hunt, MJO
Yang, M
Brach, JS
Harris, TB
Newman, AB
Satterfield, S
Studenski, SA
Yaffe, K
Aizenstein, HJ
Rosano, C
AF Rosso, Andrea L.
Hunt, Megan J. Olson
Yang, Mei
Brach, Jennifer S.
Harris, Tamara B.
Newman, Anne B.
Satterfield, Suzanne
Studenski, Stephanie A.
Yaffe, Kristine
Aizenstein, Howard J.
Rosano, Caterina
CA Hlth ABC Study
TI Higher step length variability indicates lower gray matter integrity of
selected regions in older adults
SO GAIT & POSTURE
LA English
DT Article
DE Gait disorders; Diffusion tensor imaging; Aging; Brain
ID GAIT VARIABILITY; PARKINSONS-DISEASE; MEAN DIFFUSIVITY; WALKING SPEED;
WHITE-MATTER; BRAIN; VOLUME; AGE
AB Step length variability (SLV) increases with age in those without overt neurologic disease, is higher in neurologic patients, is associated with falls, and predicts dementia. Whether higher SLV in older adults without neurologic disease indicates presence of neurologic abnormalities is unknown. Our objective was to identify whether SLV in older adults without overt disease is associated with findings from multimodal neuroimaging. A well-characterized cohort of 265 adults (79-90 years) was concurrently assessed by gait mat, magnetic resonance imaging with diffusion tensor, and neurological exam. Linear regression models adjusted for gait speed, demographic, health, and functional covariates assessed associations of MRI measures (gray matter volume, white matter hyperintensity volume, mean diffusivity, fractional anisotropy) with SLV. Regional distribution of associations was assessed by sparse partial least squares analyses. Higher SLV (mean: 8.4, SD: 3.3) was significantly associated with older age, slower gait speed, and poorer executive function and also with lower graymatter integrity measured by mean diffusivity (standardized beta = 0.16; p = 0.02). Associations between SLV and gray matter integrity were strongest for the hippocampus and anterior cingulate gyrus (both b = 0.18) as compared to other regions. Associations of SLV with other neuroimaging markers were not significant. Lower integrity of normal-appearing gray matter may underlie higher SLV in older adults. Our results highlighted the hippocampus and anterior cingulate gyrus, regions involved in memory and executive function. These findings support previous research indicating a role for cognitive function in motor control. Higher SLV may indicate focal neuropathology in those without diagnosed neurologic disease. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Rosso, Andrea L.; Yang, Mei; Newman, Anne B.; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Hunt, Megan J. Olson] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Brach, Jennifer S.] Univ Pittsburgh, Dept Phys Therapy, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Aizenstein, Howard J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
RP Rosso, AL (reprint author), 130 N Bellefield Ave,Suite 400, Pittsburgh, PA 15213 USA.
EM alr143@pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Rosso, Andrea/0000-0001-5890-9856;
Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG-028050, K23-AG-028966, R01-AG-029232,
T32-AG-000181]; NINR [R01-NR-012459]; University of Pittsburgh Claude D.
Pepper Older Americans Independence Center [P30-AG-024827-07]
FX Health ABC was supported by National Institute on Aging (NIA) Contracts
(N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG-028050,
and NINR grant R01-NR-012459). This research was supported in part by
the Intramural Research Program of the NIA (K23-AG-028966,
R01-AG-029232), the University of Pittsburgh Claude D. Pepper Older
Americans Independence Center P30-AG-024827-07, and a training grant
from the NIA (T32-AG-000181). The study sponsor had no role in the
design, analysis, or writing of this manuscript.
NR 30
TC 16
Z9 16
U1 1
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0966-6362
EI 1879-2219
J9 GAIT POSTURE
JI Gait Posture
PD MAY
PY 2014
VL 40
IS 1
BP 225
EP 230
DI 10.1016/j.gaitpost.2014.03.192
PG 6
WC Neurosciences; Orthopedics; Sport Sciences
SC Neurosciences & Neurology; Orthopedics; Sport Sciences
GA AH8KS
UT WOS:000336387300040
PM 24792638
ER
PT J
AU Mamessier, E
Broussais-Guillaumot, F
Chetaille, B
Bouabdallah, R
Xerri, L
Jaffe, ES
Nadel, B
AF Mamessier, Emilie
Broussais-Guillaumot, Florence
Chetaille, Bruno
Bouabdallah, Reda
Xerri, Luc
Jaffe, Elaine S.
Nadel, Bertrand
TI Nature and importance of follicular lymphoma precursors
SO HAEMATOLOGICA
LA English
DT Review
ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; TUMOR-ASSOCIATED MACROPHAGES;
FONDAZIONE ITALIANA LINFOMI; RANDOMIZED CONTROLLED-TRIAL; IN-SITU;
GERMINAL-CENTERS; T(14/18) TRANSLOCATION; RITUXIMAB MAINTENANCE; SOMATIC
MUTATIONS
AB It is now widely recognized that cancer development is a protracted process requiring the stepwise acquisition of multiple oncogenic events. In humans, this process can take decades, if not a lifetime, blurring the notion of `healthy' individuals. Follicular lymphoma exemplifies this multistep pathway of oncogenesis. In recent years, variants of follicular lymphoma have been recognized that appear to represent clonal B-cell expansions at an early stage of follicular lymphoma lymphomagenesis. These include follicular lymphoma in situ, duodenal follicular lymphoma, partial involvement by follicular lymphoma, and in the blood circulating follicular lymphoma-like B cells. Recent genetic studies have identified similarities and differences between the early lesions and overt follicular lymphoma, providing important information for understanding their biological evolution. The data indicate that there is already genomic instability at these early stages, even in instances with a low risk for clinical progression. The overexpression of BCL2 in t( 14; 18)-positive B cells puts them at risk for subsequent genetic aberrations when they re-enter the germinal center and are exposed to the influences of activation-induced cytidine deaminase and somatic hypermutations. The emerging data provide a rationale for clinical management and, in the future, may identify genetic risk factors that warrant early therapeutic intervention.
C1 [Mamessier, Emilie; Nadel, Bertrand] INSERM, U631, F-13258 Marseille, France.
[Mamessier, Emilie; Nadel, Bertrand] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, Marseille, France.
[Mamessier, Emilie; Broussais-Guillaumot, Florence; Chetaille, Bruno; Bouabdallah, Reda; Xerri, Luc; Nadel, Bertrand] Inst Carnot CALYM, Marseilles Calym Cevi Grp, Lyon, France.
[Broussais-Guillaumot, Florence; Bouabdallah, Reda] Inst J Paoli I Calmettes, Serv Oncohematol Adulte, F-13009 Marseille, France.
[Chetaille, Bruno; Xerri, Luc] Inst J Paoli I Calmettes, Serv Biopathol, F-13009 Marseille, France.
[Jaffe, Elaine S.] NIH, Pathol Lab, Bethesda, MD 20892 USA.
RP Mamessier, E (reprint author), INSERM, U631, F-13258 Marseille, France.
EM mamessier@ciml.univ-mrs.fr
RI Nadel, Bertrand/J-2197-2014;
OI Jaffe, Elaine/0000-0003-4632-0301
NR 99
TC 11
Z9 12
U1 1
U2 13
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAY
PY 2014
VL 99
IS 5
BP 802
EP 810
DI 10.3324/haematol.2013.085548
PG 9
WC Hematology
SC Hematology
GA AH6RD
UT WOS:000336257500007
PM 24790058
ER
PT J
AU Stringaris, K
Sekine, T
Khoder, A
Alsuliman, A
Razzaghi, B
Sargeant, R
Pavlu, J
Brisley, G
de Lavallade, H
Sarvaria, A
Marin, D
Mielke, S
Apperley, JF
Shpall, EJ
Barrett, AJ
Rezvani, K
AF Stringaris, Kate
Sekine, Takuya
Khoder, Ahmad
Alsuliman, Abdullah
Razzaghi, Bonnie
Sargeant, Ruhena
Pavlu, Jiri
Brisley, Gill
de Lavallade, Hugues
Sarvaria, Anushruthi
Marin, David
Mielke, Stephan
Apperley, Jane F.
Shpall, Elizabeth J.
Barrett, A. John
Rezvani, Katayoun
TI Leukemia-induced phenotypic and functional defects in natural killer
cells predict failure to achieve remission in acute myeloid leukemia
SO HAEMATOLOGICA
LA English
DT Article
ID RESTING NK CELLS; ACUTE MYELOGENOUS LEUKEMIA; VIRUS-INFECTED CELLS;
CYTOTOXICITY RECEPTORS; INHIBITORY RECEPTORS; LIGAND INCOMPATIBILITY;
ACTIVATING RECEPTORS; MHC MOLECULES; MISSING SELF; CLASS-I
AB The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-alpha and IFN-gamma production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-alpha production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-alpha and IFN-gamma production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival.
C1 [Stringaris, Kate; Sekine, Takuya; Khoder, Ahmad; Alsuliman, Abdullah; Razzaghi, Bonnie; Sargeant, Ruhena; Pavlu, Jiri; Brisley, Gill; de Lavallade, Hugues; Marin, David; Apperley, Jane F.] Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England.
[Sekine, Takuya; Sarvaria, Anushruthi; Shpall, Elizabeth J.; Barrett, A. John; Rezvani, Katayoun] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Mielke, Stephan] Univ Wurzburg, Wurzburg, Germany.
NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Rezvani, K (reprint author), Univ Texas Houston, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM krezvani@mdanderson.org
FU MD Anderson Cancer Center Leukemia SPORE Grant [CA100632]; Leuka
registered charity [286231]; British Society for Haematology start-up
grant
FX This research is supported in part by the MD Anderson Cancer Center
Leukemia SPORE Grant CA100632, Leuka registered charity (286231) and a
British Society for Haematology start-up grant. The sponsors of this
study are public or non-profit organizations that support science in
general. They had no role in gathering, analyzing, or interpreting the
data.
NR 50
TC 28
Z9 28
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAY
PY 2014
VL 99
IS 5
BP 836
EP 847
DI 10.3324/haematol.2013.087536
PG 12
WC Hematology
SC Hematology
GA AH6RD
UT WOS:000336257500011
PM 24488563
ER
PT J
AU Morton, LM
Gibson, TM
Clarke, CA
Lynch, CF
Weisenburger, DD
Engels, EA
AF Morton, Lindsay M.
Gibson, Todd M.
Clarke, Christina A.
Lynch, Charles F.
Weisenburger, Dennis D.
Engels, Eric A.
TI Hepatitis B or C virus infection and risk of non-Hodgkin lymphoma among
solid organ transplant recipients
SO HAEMATOLOGICA
LA English
DT Letter
DE HCV; HBV; NHL after solid organ transplantation
ID LYMPHOPROLIFERATIVE DISORDERS; LIVER-TRANSPLANTATION; COHORT; CELL
C1 [Morton, Lindsay M.; Gibson, Todd M.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Weisenburger, Dennis D.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
EM mortonli@mail.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU Intramural NIH HHS; NCCDPHP CDC HHS [U58 DP000824, 1U58 DP000807-01,
5658DP000805-04, 5U58/DP000808-05, 5U58DP000812-03, 5U58DP000817-05,
5U58DP000824-04, U58 DP000805, U58 DP000807, U58 DP000808, U58 DP000812,
U58 DP000817, U58 DP000832, U58 DP000848, U58 DP000848-04, U58DP000832,
U58DP0038789]; NCI NIH HHS [HHSN261201000024C, HHSN261201000026C,
HHSN261201000027C, HHSN261201000034C, HHSN261201000035I,
HHSN261201000036C, HHSN261201000037C, N01PC35137, N01PC35139,
N01PC35142, N01PC35143, N01PC54405, P30 CA086862]; None
[HHSN261201000035C]
NR 15
TC 4
Z9 4
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD MAY
PY 2014
VL 99
IS 5
BP E70
EP E73
DI 10.3324/haematol.2013.101600
PG 4
WC Hematology
SC Hematology
GA AH6RD
UT WOS:000336257500003
PM 24561790
ER
PT J
AU Hooker, GW
Peay, H
Erby, L
Bayless, T
Biesecker, BB
Roter, DL
AF Hooker, Gillian W.
Peay, Holly
Erby, Lori
Bayless, Theodore
Biesecker, Barbara B.
Roter, Debra L.
TI Genetic Literacy and Patient Perceptions of IBD Testing Utility and
Disease Control: A Randomized Vignette Study of Genetic Testing
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE genetic testing; genetic literacy; IBD
ID INFLAMMATORY-BOWEL-DISEASE; NUMERACY; NUMBER; LOCI
AB Background: Findings from inflammatory bowel disease (IBD) genome-wide association studies are being translated clinically into prognostic and diagnostic indicators of disease. Yet, patient perception and understanding of these tests and their applicability to providing risk information is unclear. The goal of this study was to determine, using hypothetical scenarios, whether patients with IBD perceive genetic testing to be useful for risk assessment, whether genetic test results impact perceived control, and whether low genetic literacy may be a barrier to patient understanding of these tests. Methods: Two hundred fifty seven patients with IBD from the Johns Hopkins gastroenterology clinics were randomized to receive a vignette depicting either a genetic testing scenario or a standard blood testing scenario. Participants were asked questions about the vignette and responses were compared between groups. Results: Perceptions of test utility for risk assessment were higher among participants responding to the genetic vignette (P < 0.001). There were no significant differences in perceptions of control over IBD after hypothetical testing between vignettes (P = 0.24). Participant responses were modified by genetic literacy, measured using a scale developed for this study. Participants randomized to the genetic vignette who scored higher on the genetic literacy scale perceived greater utility of testing for risk assessment (P = 0.008) and more control after testing (P = 0.02). Conclusions: Patients with IBD perceive utility in genetic testing for providing information relevant to family members, and this appreciation is promoted by genetic literacy. Low genetic literacy among patients poses a potential threat to effective translation of genetic and genomic tests.
C1 [Hooker, Gillian W.; Peay, Holly; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Erby, Lori; Roter, Debra L.] Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA.
[Erby, Lori; Roter, Debra L.] Johns Hopkins Sch Publ Hlth, Ctr Genom Literacy & Commun, Baltimore, MD 21205 USA.
[Bayless, Theodore] Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21205 USA.
RP Roter, DL (reprint author), Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, 624N Broadway, Baltimore, MD 21205 USA.
EM droter@jhsph.edu
RI Roter, Debra/N-8830-2014
FU Intramural Research program of the National Human Genome Research
Institute, National Institutes of Health
FX This research was supported by the Intramural Research program of the
National Human Genome Research Institute, National Institutes of Health.
The authors thank Dr. Steven Brant and Dr. Susan Hutfless for their
comments on the manuscript and Cris Price of Abt Associates for data
analysis support.
NR 23
TC 5
Z9 5
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD MAY
PY 2014
VL 20
IS 5
BP 901
EP 908
DI 10.1097/MIB.0000000000000021
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH0CU
UT WOS:000335787500015
PM 24691112
ER
PT J
AU Chong, WP
Horai, R
Mattapallil, MJ
Silver, PB
Chen, J
Zhou, R
Sergeev, Y
Villasmil, R
Chan, CC
Caspi, RR
AF Chong, Wai Po
Horai, Reiko
Mattapallil, Mary J.
Silver, Phyllis B.
Chen, Jun
Zhou, Ru
Sergeev, Yuri
Villasmil, Rafael
Chan, Chi-Chao
Caspi, Rachel R.
TI IL-27p28 inhibits central nervous system autoimmunity by concurrently
antagonizing Th1 and Th17 responses
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Autoimmunity; gp130; IL-27p28
ID CD4(+) T-CELLS; CYTOKINE GM-CSF; T(H)17 CELLS; INTERFERON-GAMMA;
TERMINAL DIFFERENTIATION; EFFECTOR RESPONSE; HELPER-CELLS; UVEITIS;
ENCEPHALOMYELITIS; RECEPTOR
AB Central nervous system (CNS) autoimmunity such as uveitis and multiple sclerosis is accompanied by Th1 and Th17 responses. In their corresponding animal models, experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE), both responses are induced and can drive disease independently. Because immune responses have inherent plasticity, therapeutic targeting of only one pathway could promote the other, without reducing pathology. IL-27p28 antagonizes gp130, required for signaling by IL-27 and IL-6, which respectively promote Th1 and Th17 responses. We therefore examined its ability to protect the CNS by concurrently targeting both effector responses. Overexpression of IL-27p28 in vivo ameliorated EAU as well as EAE pathology and reduced tissue infiltration by Th1 and Th17 cells in a disease prevention, as well as in a disease reversal protocol. Mechanistic studies revealed inhibition of Th1 and Th17 commitment in vitro and decreased lineage stability of pre-formed effectors in vivo, with reduction in expression of gp 130-dependent transcription factors and cytokines. Importantly, IL-27p28 inhibited polarization of human T cells to the Th1 and Th17 effector pathways. The ability of IL-27p28 to inhibit generation as well as function of pathogenic Th1 and Th17 effector cells has therapeutic implications for controlling immunologically complex autoimmune diseases. Published by Elsevier Ltd.
C1 [Chong, Wai Po; Horai, Reiko; Mattapallil, Mary J.; Silver, Phyllis B.; Chen, Jun; Zhou, Ru; Chan, Chi-Chao; Caspi, Rachel R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Sergeev, Yuri] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Villasmil, Rafael] NEI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222,10 Ctr Dr, Bethesda, MD 20892 USA.
EM caspir@nei.nih.gov
OI Caspi, Rachel/0000-0002-7140-7671
FU NIH/NEI Intramural funding [EY000184-29]
FX The authors thank the NEI the Flow Cytometry Core and Histology
facilities. We thank Dr. Wei Lai for technical advice on human T cell
polarization. We thank Olivia Schneider of Shenandoah Biotechnology for
the IL-27p28 plasmid. We are grateful to Dr. Christopher Hunter
(University of Pennsylvania) for supplying to us the ZymoGenetics p28 TG
mice. The study was supported by NIH/ NEI Intramural funding, project #
EY000184-29.
NR 59
TC 16
Z9 18
U1 0
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD MAY
PY 2014
VL 50
BP 12
EP 22
DI 10.1016/j.jaut.2013.08.003
PG 11
WC Immunology
SC Immunology
GA AH4RB
UT WOS:000336114600002
PM 24021664
ER
PT J
AU Li, B
Cui, WP
Tan, Y
Luo, P
Chen, Q
Zhang, C
Qu, W
Miao, LN
Cai, L
AF Li, Bing
Cui, Wenpeng
Tan, Yi
Luo, Ping
Chen, Qiang
Zhang, Chi
Qu, Wei
Miao, Lining
Cai, Lu
TI Zinc is essential for the transcription function of Nrf2 in human renal
tubule cells in vitro and mouse kidney in vivo under the diabetic
condition
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE Akt phosphorylation; diabetic nephropathy; Fyn; Nrf2; TPEN; zinc
chelation
ID OXIDATIVE STRESS; NF-E2-RELATED FACTOR-2; ENDOTHELIAL-CELLS; MELLITUS
PATIENTS; PROTECTIVE ROLE; SUPPLEMENTATION; DEFICIENCY; RATS;
NEPHROPATHY; METALLOTHIONEIN
AB Increasing evidence from human and laboratory studies showed the effect of zinc (Zn) on diabetic complications. Nuclear factor-erythroid 2-related factor 2 (Nrf2) plays important role in the prevention of oxidative damage. This study was to define whether Zn statues (deficiency or supplement) affect the Nrf2 expression and function, and also affect the damage severity of human renal tubular (HK11) cells exposed to high glucose (HG) with palmitate (Pal) and kidney of diabetic mice induced by multiple low-dose streptozotocins. For Zn deficiency diabetic mice were treated with Zn chelator PTEN at 5mg/kg bw daily for 4months. Results showed that HG/Pal significantly increased the expression of pro-fibrotic mediators, connective tissue growth factor and PAI-1, in HK11 cells, which was exacerbated by TPEN that depleted intracellular free Zn and decreased Nrf2 expression and transcription. Zn supplement prevented the effects of TPEN and also increased Akt and GSK-3 phosphorylation with a decrease in Nrf2 nuclear exporter, Fyn. All these effects of Zn were abolished by Akt inhibitor. Therefore, Zn up-regulates Nrf2 function via activating Akt-mediated inhibition of Fyn function. Treatment of diabetic mice with TPEN decreased renal Zn level and Nrf2 expression and transcription, with an exacerbation of renal oxidative damage, inflammation and fibrosis. These results suggest the essentiality of Zn for Nrf2 expression and transcription function.
C1 [Li, Bing; Cui, Wenpeng; Luo, Ping; Miao, Lining] Jilin Univ, Hosp 2, Dept Nephrol, Changchun 130041, Peoples R China.
[Li, Bing; Cui, Wenpeng; Tan, Yi; Chen, Qiang; Zhang, Chi; Cai, Lu] Univ Louisville, Kosair Childrens Hosp Res Inst, Louisville, KY 40292 USA.
[Li, Bing; Cui, Wenpeng; Tan, Yi; Chen, Qiang; Zhang, Chi; Cai, Lu] Univ Louisville, Dept Pediat, Louisville, KY 40292 USA.
[Li, Bing; Cui, Wenpeng; Tan, Yi; Chen, Qiang; Zhang, Chi; Cai, Lu] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Li, Bing] Jilin Prov Peoples Hosp, Dept Nephrol, Changchun, Peoples R China.
[Tan, Yi; Zhang, Chi; Cai, Lu] Wenzhou Med Univ, Chinese Amer Res Inst Diabet Complicat, Wenzhou, Peoples R China.
[Qu, Wei] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Cai, Lu] Univ Louisville, Dept Radiat Oncol, Louisville, KY 40292 USA.
RP Miao, LN (reprint author), Jilin Univ, Hosp 2, 218 Ziqiang St, Changchun 130041, Peoples R China.
EM mlnkidney@163.com; L0cai001@louisville.edu
FU American Diabetes Association [1-13-JF-53]; Science and Technology
Activities Start-Up Project of Returned Overseas Chinese Talents;
Natural Science Foundation of China [81273509, 81200525]; Key Science
and Technology Development Plan from Wenzhou City [Y20100001]; National
Natural Science Foundation of China [81170669]; Director Funds of the
National Natural Science Foundation of China [81241023]; China
Scholarship Council
FX We thank Dr. Rane J Madhavi, Department of Medicine at the University of
Louisville, School of Medicine, for her providing HK11 cells to us as
gift. We are grateful to Dr. Nicholas Mellen, Department of Pediatrics
at the University of Louisville, and Drs. Katie Pelch and Yuanyuan Xu,
National Toxicology Program Laboratory, Division at the National
Toxicology Program, NIEHS, for their critical review of this manuscript.
This study was supported in part by Junior Faculty Award from American
Diabetes Association (1-13-JF-53, to YT), Science and Technology
Activities Start-Up Project of Returned Overseas Chinese Talents in 2012
(to BL), Natural Science Foundation of China (81273509, to YT; 81200525,
to WC), Key Science and Technology Development Plan from Wenzhou City
(Y20100001, to YT), the National Natural Science Foundation of China
(81170669, to LM), and the Director Funds of the National Natural
Science Foundation of China (81241023, to PL). B. Li was a recipient of
Scholarship under State Scholarship Fund from China Scholarship Council.
NR 53
TC 21
Z9 21
U1 2
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD MAY
PY 2014
VL 18
IS 5
BP 895
EP 906
DI 10.1111/jcmm.12239
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA AH1EB
UT WOS:000335861500015
PM 24597671
ER
PT J
AU Portnoy, DB
Leach, CR
Kaufman, AR
Moser, RP
Alfano, CM
AF Portnoy, David B.
Leach, Corinne R.
Kaufman, Annette R.
Moser, Richard P.
Alfano, Catherine M.
TI Reduced Fatalism and Increased Prevention Behavior After Two
High-Profile Lung Cancer Events
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
ID NATIONAL TRENDS SURVEY; BREAST-CANCER; INFORMATION-SEEKING; HEALTH
INFORMATION; NEWS COVERAGE; AFRICAN-AMERICAN; IMPACT; RISK; BELIEFS;
WOMEN
AB The positive impact of media coverage of high-profile cancer events on cancer prevention behaviors is well-established. However, less work has focused on potential adverse psychological reactions to such events, such as fatalism. Conducting 3 studies, the authors explored how the lung cancer death of Peter Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a national media sample in Study 1 found that media coverage of these events often focused on reiterating the typical profile of those diagnosed with lung cancer; 38% of the media mentioned at least 1 known risk factor for lung cancer, most often smoking. Data from a nationally representative survey in Study 2 found that respondents reported lower lung cancer fatalism, after, compared with before, the events (OR=0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to the national tobacco Quitline after these events was found in Study 3. These results suggest that there is a temporal association between high-profile cancer events, the subsequent media coverage, psychological outcomes, and cancer prevention behaviors. These results suggest that high-profile cancer events could be leveraged as an opportunity for large-scale public heath communication campaigns through the dissemination of cancer prevention messages and services.
C1 [Portnoy, David B.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD USA.
[Portnoy, David B.; Kaufman, Annette R.; Moser, Richard P.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
[Leach, Corinne R.] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30329 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Portnoy, DB (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd,CORP 330H, Rockville, MD 20850 USA.
EM david.portnoy@fda.hhs.gov
OI Portnoy, David/0000-0003-2175-9457
FU Intramural NIH HHS [Z99 CA999999]
NR 42
TC 0
Z9 0
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD MAY 1
PY 2014
VL 19
IS 5
BP 577
EP 592
DI 10.1080/10810730.2013.821553
PG 16
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA AH1EC
UT WOS:000335861600005
PM 24274730
ER
PT J
AU Salomon, DG
Fermento, ME
Gandini, NA
Ferronato, MJ
Arevalo, J
Blasco, J
Andres, NC
Zenklusen, JC
Curino, AC
Facchinetti, MM
AF Salomon, Debora G.
Fermento, Maria E.
Gandini, Norberto A.
Ferronato, Maria J.
Arevalo, Julian
Blasco, Jorge
Andres, Nancy C.
Zenklusen, Jean C.
Curino, Alejandro C.
Facchinetti, Maria M.
TI Vitamin D receptor expression is associated with improved overall
survival in human glioblastoma multiforme
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Vitamin D receptor; Human GBM; Tissue microarray; Biomarker; Survival;
Prognosis
ID GLIOMA-CELL LINE; PROGNOSTIC-FACTOR; BREAST-CANCER; BRAIN-TUMORS;
ASTROCYTIC GLIOMAS; GENE-EXPRESSION; VDR EXPRESSION; CALCITRIOL;
INDUCTION; CARCINOMA
AB Vitamin D and its analogs have been shown to display anti-proliferative effects in a wide variety of cancer types including glioblastoma multiforme (GBM). These anticancer effects are mediated by its active metabolite, 1 alpha, 25-dihydroxyvitamin D-3 (calcitriol) acting mainly through vitamin D receptor (VDR) signaling. In addition to its involvement in calcitriol action, VDR has also been demonstrated to be useful as a prognostic factor for some types of cancer. However, to our knowledge, there are no studies evaluating the expression of VDR protein and its association with outcome in gliomas. Therefore, we investigated VDR expression by using immunohistochemical analysis in human glioma tissue microarrays, and analyzed the association between VDR expression and clinico-pathological parameters. We further investigated the effects of genetic and pharmacologic modulation of VDR on survival and migration of glioma cell lines. Our data demonstrate that VDR is increased in tumor tissues when compared with VDR in non-malignant brains, and that VDR expression is associated with an improved outcome in patients with GBM. We also show that both genetic and pharmacologic modulation of VDR modulates GBM cellular migration and survival and that VDR is necessary for calcitriol-mediated effects on migration. Altogether these results provide some limited evidence supporting a role for VDR in glioma progression.
C1 [Salomon, Debora G.; Fermento, Maria E.; Gandini, Norberto A.; Ferronato, Maria J.; Andres, Nancy C.; Curino, Alejandro C.; Facchinetti, Maria M.] Inst Invest Bioquim Bahia Blanca INIBIBB CONICET, Ctr Cient Tecnol Bahia Blanca, Lab Biol Canc, RA-8000 Bahia Blanca, Buenos Aires, Argentina.
[Arevalo, Julian; Blasco, Jorge] Hosp Interzonal Gen Agudos Dr Jose Penna, Serv Patol, Bahia Blanca, Buenos Aires, Argentina.
[Zenklusen, Jean C.] NCI, Off Canc Genom, NIH, Bethesda, MD 20892 USA.
RP Facchinetti, MM (reprint author), Inst Invest Bioquim Bahia Blanca INIBIBB CONICET, Ctr Cient Tecnol Bahia Blanca, Lab Biol Canc, Camino La Carrindanga Km 7 C-C 857, RA-8000 Bahia Blanca, Buenos Aires, Argentina.
EM facchinm@criba.edu.ar
OI Andres, Nancy Carolina/0000-0002-6756-8878
FU National Council of Scientific and Technical Research (CONICET);
National Agency for the Promotion of Science and Technology (ANPCyT);
Technical Secretary of the Universidad Nacional del Sur
FX This work was supported by grants from National Council of Scientific
and Technical Research (CONICET), National Agency for the Promotion of
Science and Technology (ANPCyT) and from the Technical Secretary of the
Universidad Nacional del Sur. D. Salomon is a recipient of fellowship
from Conicet.
NR 58
TC 4
Z9 4
U1 0
U2 8
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 MAY
PY 2014
VL 118
IS 1
BP 49
EP 60
DI 10.1007/s11060-014-1416-3
PG 12
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AH8HC
UT WOS:000336376700006
PM 24584679
ER
PT J
AU Dowling, MM
Noetzel, MJ
Rodeghier, MJ
Quinn, CT
Hirtz, DG
Ichord, RN
Kwiatkowski, JL
Roach, ES
Kirkham, FJ
Casella, JF
DeBaun, MR
AF Dowling, Michael M.
Noetzel, Michael J.
Rodeghier, Mark J.
Quinn, Charles T.
Hirtz, Deborah G.
Ichord, Rebecca N.
Kwiatkowski, Janet L.
Roach, E. Steven
Kirkham, Fenella J.
Casella, James F.
DeBaun, Michael R.
TI Headache and Migraine in Children with Sickle Cell Disease Are
Associated with Lower Hemoglobin and Higher Pain Event Rates But Not
Silent Cerebral Infarction
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID BRAIN INFARCTS; ANEMIA; ADOLESCENTS; ABNORMALITIES; CRITERIA;
PREVALENCE; MANAGEMENT; DISORDERS; DIAGNOSIS; OVERUSE
AB Objective To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts.
Study design In this cross-sectional study, we evaluated the health history, laboratory values, and brain magnetic resonance imaging findings of participants with sickle cell disease (hemoglobinSS or hemoglobinS beta degrees-thalassemia) with no history of overt stroke or seizures. Participants characterized headache severity and quality. Migraine was defined by International Headache Society criteria modified for increased sensitivity in children. Neuroradiology and neurology committees adjudicated the presence of silent cerebral infarction by review of magnetic resonance imaging and standardized examination by pediatric neurologists.
Results The cohort included 872 children (51.1% males), ranging in age from 5 to 15 years (mean age, 9.1 years). Of these children, 317 (36.4%) reported recurrent headaches, and 132 (15.1%) reported migraines. In multivariable logistic regression analyses, both were associated with lower steady-state hemoglobin (P = .01 for headaches; P < .01 for migraines) and higher pain rate (P < .01 for headaches; P < .01 for migraines), defined as the number of admissions requiring opioids in the previous 3 years. The presence of silent cerebral infarction was not associated with recurrent headaches or migraines. Only 1.9% (6 of 317) of children with recurrent headaches received medication for headache prophylaxis.
Conclusion Recurrent headaches and migraines are common and un-dertreated in children with sickle cell disease. Low hemoglobin levels and high pain rates are associated with recurrent headaches and migraines; whereas, silent cerebral infarction is not.
C1 [Dowling, Michael M.] Univ Texas SW Med Ctr Dallas, Dept Pediat & Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Noetzel, Michael J.] St Louis Childrens Hosp, Div Pediat & Dev Neurol, Dept Neurol, St Louis, MO 63178 USA.
[Noetzel, Michael J.] Washington Univ, Sch Med, St Louis, MO USA.
[Rodeghier, Mark J.] Rodeghier Consultants, Chicago, IL USA.
[Quinn, Charles T.] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Hematol, Cincinnati, OH 45229 USA.
[Hirtz, Deborah G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Ichord, Rebecca N.; Kwiatkowski, Janet L.] Univ Penn, Childrens Hosp Philadelphia, Dept Neurol & Pediat, Philadelphia, PA 19104 USA.
[Ichord, Rebecca N.; Kwiatkowski, Janet L.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Roach, E. Steven] Ohio State Coll Med, Div Child Neurol, Columbus, OH USA.
[Kirkham, Fenella J.] UCL, Inst Child Hlth, Inst Neurosci, London, England.
[Casella, James F.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Hematol, Baltimore, MD 21205 USA.
[DeBaun, Michael R.] Vanderbilt Univ, Sch Med, Vanderbilt Meharry Matthew Walker Ctr Excellence, Dept Pediat, Nashville, TN 37232 USA.
RP DeBaun, MR (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Meharry Matthew Walker Ctr Excellence, 2200 Childrens Way,Room 11206 DOT, Nashville, TN 37232 USA.
EM m.debaun@vanderbilt.edu
RI Quinn, Charles/J-6842-2012; Kirkham, Fenella/C-2442-2009
OI Quinn, Charles/0000-0002-2372-2175; Kirkham, Fenella/0000-0002-2443-7958
FU National Institutes of Health [U01-NS042804]; North and Central Texas
Clinical and Translational Science Initiative from the NIH [KL2
RR024983]; Doris Duke Charitable Foundation; First American Real Estate
Information Services, Inc.; Johns Hopkins
FX Supported by the National Institutes of Health (U01-NS042804). M. D. and
C. Q. were supported by the North and Central Texas Clinical and
Translational Science Initiative from the NIH (KL2 RR024983), and M. D.
is supported by the Doris Duke Charitable Foundation and First American
Real Estate Information Services, Inc. J.C. has received an honorarium
and travel expenses in the past and presently receives salary support
through Johns Hopkins for providing consultative advice to Adventrx
Pharmaceuticals regarding a proposed clinical trial of an agent for
treating vaso-occlusive crisis in sickle cell disease, and is an
inventor and a named party on a patent and licensing agreement to
ImmunArray for a panel of brain biomarkers for the detection of brain
injury. Neither company had input into the design, analysis,
interpretation, or content of this study and did not influence the
decision to submit this manuscript. The contents of this article
represent the personal opinion of the authors and should not be
construed as the opinion or position of the National Institutes of
Health or its affiliates. The other authors declare no conflicts of
interest.
NR 40
TC 8
Z9 8
U1 0
U2 2
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 MAY
PY 2014
VL 164
IS 5
BP 1175
EP +
DI 10.1016/j.jpeds.2014.01.001
PG 7
WC Pediatrics
SC Pediatrics
GA AG6GB
UT WOS:000335516000046
PM 24529619
ER
PT J
AU Lansford, JE
Deater-Deckard, K
Bornstein, MH
Putnick, DL
Bradley, RH
AF Lansford, Jennifer E.
Deater-Deckard, Kirby
Bornstein, Marc H.
Putnick, Diane L.
Bradley, Robert H.
TI Attitudes Justifying Domestic Violence Predict Endorsement of Corporal
Punishment and Physical and Psychological Aggression towards Children: A
Study in 25 Low- and Middle-Income Countries
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID PARENTS
AB Objective The Convention on the Rights of the Child has prompted countries to protect children from abuse and exploitation. Exposure to domestic violence and corporal punishment are risk factors in children's development. This study investigated how women's attitudes about domestic violence are related to attitudes about corporal punishment and harsh behaviors toward children, and whether country-wide norms regarding domestic violence and corporal punishment are related to psychological aggression and physical violence toward children.
Study design Data were drawn from the Multiple Indicator Cluster Survey, a nationally representative and internationally comparable household survey developed by the United Nations Children's Fund. Measures of domestic violence and discipline were completed by 85 999 female caregivers of children between the ages of 2 and 14 years from families in 25 low-and middle-income countries.
Results Mothers who believed that husbands were justified in hitting their wives were more likely to believe that corporal punishment is necessary to rear children. Mothers who believed that husbands were justified in hitting their wives and that corporal punishment is necessary to rear children were more likely to report that their child had experienced psychological aggression and physical violence. Countrywide norms regarding the acceptability of husbands hitting wives and advisability of corporal punishment moderated the links between mothers' attitudes and their behaviors toward children.
Conclusions Pediatricians can address parents' psychological aggression and physical violence toward children by discussing parents' attitudes and behaviors within a framework that incorporates social norms regarding the acceptability of domestic violence and corporal punishment.
C1 [Lansford, Jennifer E.] Duke Univ, Ctr Child & Family Policy, Durham, NC 27708 USA.
[Deater-Deckard, Kirby] Virginia Tech Univ, Dept Psychol, Blacksburg, VA USA.
[Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Bradley, Robert H.] Arizona State Univ, Dept Psychol, Sch Social & Family Dynam, Tempe, AZ 85287 USA.
RP Lansford, JE (reprint author), Duke Univ, Ctr Child & Family Policy, Box 90545, Durham, NC 27708 USA.
EM lansford@duke.edu
OI Putnick, Diane/0000-0002-6323-749X
FU NICHD NIH HHS [R01 HD054805]
NR 16
TC 7
Z9 7
U1 0
U2 14
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 MAY
PY 2014
VL 164
IS 5
BP 1208
EP 1213
DI 10.1016/j.jpeds.2013.11.060
PG 6
WC Pediatrics
SC Pediatrics
GA AG6GB
UT WOS:000335516000051
PM 24412139
ER
PT J
AU Maltsev, VA
Yaniv, Y
Maltsev, AV
Stern, MD
Lakatta, EG
AF Maltsev, Victor A.
Yaniv, Yael
Maltsev, Anna V.
Stern, Michael D.
Lakatta, Edward G.
TI Modern Perspectives on Numerical Modeling of Cardiac Pacemaker Cell
SO JOURNAL OF PHARMACOLOGICAL SCIENCES
LA English
DT Review
DE cardiac pacemaker; sinoatrial node cell; numerical modeling; calcium;
ion channel
ID RABBIT SINOATRIAL NODE; HODGKIN-HUXLEY EQUATIONS; SUSTAINED INWARD
CURRENT; SPONTANEOUS BEATING RATE; RHYTHMIC CA2+ CLOCK;
SUPPLY-AND-DEMAND; CURRENT I-F; SARCOPLASMIC-RETICULUM;
MATHEMATICAL-MODEL; INTRACELLULAR CALCIUM
AB Cardiac pacemaking is a complex phenomenon that is still not completely understood. Together with experimental studies, numerical modeling has been traditionally used to acquire mechanistic insights in this research area. This review summarizes the present state of numerical modeling of the cardiac pacemaker, including approaches to resolve present paradoxes and controversies. Specifically we discuss the requirement for realistic modeling to consider symmetrical importance of both intracellular and cell membrane processes (within a recent "coupled-clock" theory). Promising future developments of the complex pacemaker system models include the introduction of local calcium control, mitochondria function, and biochemical regulation of protein phosphorylation and cAMP production. Modern numerical and theoretical methods such as multi-parameter sensitivity analyses within extended populations of models and bifurcation analyses are also important for the definition of the most realistic parameters that describe a robust, yet simultaneously flexible operation of the coupled-clock pacemaker cell system. The systems approach to exploring cardiac pacemaker function will guide development of new therapies such as biological pacemakers for treating insufficient cardiac pacemaker function that becomes especially prevalent with advancing age.
C1 [Maltsev, Victor A.; Yaniv, Yael; Stern, Michael D.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Maltsev, Anna V.] Univ Bristol, Dept Math, Bristol BS8 1TW, Avon, England.
RP Maltsev, VA (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM MaltsevVi@mail.nih.gov
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
FU Intramural Research Program of the 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 140
TC 7
Z9 7
U1 0
U2 16
PU JAPANESE PHARMACOLOGICAL SOC
PI KYOTO
PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604,
JAPAN
SN 1347-8613
EI 1347-8648
J9 J PHARMACOL SCI
JI J. Pharmacol. Sci.
PD MAY
PY 2014
VL 125
IS 1
BP 6
EP 38
DI 10.1254/jphs.13R04CR
PG 33
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AI0RH
UT WOS:000336556600002
PM 24748434
ER
PT J
AU Levy, G
Hill, M
Beall, S
Pilgrim, JD
Payson, M
Propst, A
AF Levy, Gary
Hill, Micah
Beall, Stephanie
Pilgrim, Justin D.
Payson, Mark
Propst, Anthony
TI Falling Estradiol Levels on Day After Human Chorionic Gonadotropin
Administration in Assisted Reproductive Technology Cycles Are Not
Predictive of Decreasing Oocyte Maturity or Pregnancy Rates
SO JOURNAL OF REPRODUCTIVE MEDICINE
LA English
DT Article
DE assisted reproductive technologies; estradiol; oocyte maturity; ovarian
stimulation
ID IN-VITRO FERTILIZATION; OVARIAN HYPERSTIMULATION SYNDROME; TRANSFER
IVF-ET; EMBRYO-TRANSFER; HCG INJECTION; STIMULATION; ASSOCIATION;
PATTERN
AB OBJECTIVE: To determine whether a fall in serum estradiol levels the day after human chorionic gonadotropin (hCG) administration correlated with the incidence of a positive serum hCG in fresh, nondonor assisted reproductive technology (ART) cycles.
STUDY DESIGN: A total of 1,969 women undergoing fresh, nondonor ART cycles at a tertiary referral fertility clinic between January 1, 2003, and January 31, 2010, were included and spectively analyzed. Primary outcome measures were oocyte maturity and positive serum beta-hCG.
RESULTS: A total of 1,969 cycles met inclusion criteria, of which 1,875 had the same or increasing serum estradiol levels and 94 had decreasing estradiol levels on the morning after hCG trigger administration (6-11 hours after hCG injection). There were no statistically significant differences between the groups with respect to age, baseline FSH levels, type of pituitary downregulation, total ampules of gonadotropin administered, days of stimulation,, average number of oocytes retrieved, or oocyte maturity. Probability of pregnancy in women with declining E2 lavels after hCG trigger administration did not differ from patients with the same or rising estradiol levels (53% vs. 54%, p = 0.89).
CONCLUSION: Absolute change in estradiol levels the morning after beta-hCG administration were not predictive of positive hCG.
C1 Walter Reed Natl Mil Med Ctr, Dept Reprod Endocrinol & Infertil, Bethesda, MD USA.
Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
Natl Inst Child Hlth & Human Dev, Program Reprod & Adult Endocrinol, Bethesda, MD 20889 USA.
Bayne Jones Army Community Hosp, Ft Polk, LA USA.
RP Levy, G (reprint author), Natl Inst Child Hlth & Human Dev, Program Adult & Reprod Endocrinol, Dept Reprod Endocrinol & Infertil, Combined Dept Obstet & Gynecol,Walter Reed Natl M, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM garylevy1@gmail.com
FU Intramural NIH research Program in Reproductive and Adult Endocrinology
FX This research is supported in part by the Intramural NIH research
Program in Reproductive and Adult Endocrinology.
NR 14
TC 1
Z9 1
U1 0
U2 0
PU SCI PRINTERS & PUBL INC
PI ST LOUIS
PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA
SN 0024-7758
EI 1943-3565
J9 J REPROD MED
JI J. Reprod. Med.
PD MAY-JUN
PY 2014
VL 59
IS 5-6
BP 255
EP 259
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AH8WS
UT WOS:000336419500014
PM 24937966
ER
PT J
AU Xu, MJ
Feng, DC
Wang, H
Guan, YF
Yan, XQ
Gao, B
AF Xu, Ming-Jiang
Feng, Dechun
Wang, Hua
Guan, Youfei
Yan, Xiaoqiang
Gao, Bin
TI IL-22 Ameliorates Renal Ischemia-Reperfusion Injury by Targeting
Proximal Tubule Epithelium
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; FAILURE; CELLS; APOPTOSIS; PATHWAYS; JAK/STAT;
PATHOPHYSIOLOGY; PROLIFERATION; EPIDEMIOLOGY; ACTIVATION
AB The glomerular basement membrane (GBM) is a specialized extracellular matrix (ECM) compartment within the glomerulus that contains tissue-restricted isoforms of collagen IV and laminin. It is integral to the capillary wall and therefore, functionally linked to glomerular filtration. Although the composition of the GBM has been investigated with global and candidate-based approaches, the relative contributions of glomerular cell types to the production of ECM are not well understood. To characterize specific cellular contributions to the GBM, we used mass spectrometry-based proteomics to analyze ECM isolated from podocytes and glomerular endothelial cells in vitro. These analyses identified cell type-specific differences in ECM composition, indicating distinct contributions to glomerular ECM assembly. Coculture of podocytes and endothelial cells resulted in an altered composition and organization of ECM compared with monoculture ECMs, and electron microscopy revealed basement membrane-like ECM deposition between cocultured cells, suggesting the involvement of cell-cell cross-talk in the production of glomerular ECM. Notably, compared with monoculture ECM proteomes, the coculture ECM proteome better resembled a tissue-derived glomerular ECM dataset, indicating its relevance to GBM in vivo. Protein network analyses revealed a common core of 35 highly connected structural ECM proteins that may be important for glomerular ECM assembly. Overall, these findings show the complexity of the glomerular ECM and suggest that both ECM composition and organization are context-dependent.
C1 [Xu, Ming-Jiang; Feng, Dechun; Wang, Hua; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Xu, Ming-Jiang; Guan, Youfei] Peking Univ, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol, Sch Basic Med Sci,Hlth Sci Ctr,Minist Educ, Beijing 100871, Peoples R China.
[Yan, Xiaoqiang] Generon Corp, Shanghai, Peoples R China.
RP Xu, MJ (reprint author), Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100871, Peoples R China.
EM mingjiangxu@bjmu.edu.cn; bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016
FU National Institute of Alcohol Abuse and Alcoholism; National Institutes
of Health; National Natural Science Foundation of China [81270370]
FX This work was supported by the intramural program of the National
Institute of Alcohol Abuse and Alcoholism and the National Institutes of
Health (B.G.) and National Natural Science Foundation of China Grant
81270370 (to M.-J.X.).
NR 28
TC 12
Z9 12
U1 0
U2 6
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2014
VL 25
IS 5
BP 967
EP 977
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA AG7FM
UT WOS:000335583700016
PM 24459233
ER
PT J
AU Aseem, O
Smith, BT
Cooley, MA
Wilkerson, BA
Argraves, KM
Remaley, AT
Argraves, WS
AF Aseem, Obaidullah
Smith, Brian T.
Cooley, Marion A.
Wilkerson, Brent A.
Argraves, Kelley M.
Remaley, Alan T.
Argraves, W. Scott
TI Cubilin Maintains Blood Levels of HDL and Albumin
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; PROXIMAL TUBULE CELLS;
RECEPTOR-ASSOCIATED PROTEIN; APOLIPOPROTEIN-A-I; CARDIOVASCULAR-DISEASE;
BINDING PROTEIN; SERUM-ALBUMIN; THYROID-CELLS; NEONATAL RAT
AB Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL.
C1 [Aseem, Obaidullah; Smith, Brian T.; Cooley, Marion A.; Wilkerson, Brent A.; Argraves, Kelley M.; Argraves, W. Scott] Med Univ S Carolina, Regenerat Med & Cell Biol Dept, Charleston, SC 29425 USA.
[Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Argraves, WS (reprint author), Med Univ S Carolina, Regenerat Med & Cell Biol Dept, 173 Ashley Avenue, Charleston, SC 29425 USA.
EM argraves@musc.edu
FU National Institutes of Health [HL061873, HL094883]; American Heart
Association [10PRE3870038, 10PRE3910006]
FX This work was supported by National Institutes of Health grants HL061873
(W.S.A.) and HL094883 (K.M.A.). O.A. was supported by a predoctoral
fellowship from the American Heart Association (10PRE3870038). B.A.W.
was supported by a predoctoral fellowship from the American Heart
Association (10PRE3910006).
NR 50
TC 10
Z9 10
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAY
PY 2014
VL 25
IS 5
BP 1028
EP 1036
DI 10.1681/ASN.2013060671
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA AG7FM
UT WOS:000335583700021
PM 24357674
ER
PT J
AU Parks, CG
De Roos, AJ
AF Parks, C. G.
De Roos, A. J.
TI Pesticides, chemical and industrial exposures in relation to systemic
lupus erythematosus
SO LUPUS
LA English
DT Article
DE environmental risk factors; pesticides; occupational exposures;
epidemiology; silica; Systemic lupus erythematosus
ID OCCUPATIONAL RISK-FACTORS; RHEUMATOID-ARTHRITIS; ANTINUCLEAR ANTIBODIES;
ORGANOCHLORINE PESTICIDES; AUTOIMMUNE-DISEASE; CRYSTALLINE SILICA;
ASBESTOS EXPOSURE; KIDNEY-DISEASE; UNITED-STATES; MURINE LUPUS
AB Growing evidence suggests exposure to chemicals and industrial pollutants may increase risk of systemic lupus erythematosus (SLE). Here we review research on SLE associations with occupational and industrial exposures, primarily drawing on studies in human populations and summarizing epidemiologic research published in the past decade. The association of occupational silica exposure with SLE is well established, but key questions remain, including the required dose and susceptibility factors, and SLE risk due to other silicate exposures. Research on SLE and other exposures is less well developed, though several potential associations merit further consideration because of the consistency of preliminary human findings, experimental animal research, and biologic plausibility. These include pesticides and solvents, for which experimental findings also support investigation of specific agents, including organochlorines and trichloroethylene. Experimental findings and biologic plausibility suggest research on SLE and occupational exposure to hydrocarbons (i.e. mineral oils) is warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family-based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g. antinuclear antibodies), clinical features (e.g. nephritis), and outcomes.
C1 [Parks, C. G.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27599 USA.
[De Roos, A. J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA USA.
RP Parks, CG (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Res Triangle Pk, NC 27599 USA.
EM Parks1@mail.nih.gov
OI Parks, Christine/0000-0002-5734-3456
FU National Institutes of Health (NIH), National Institute of Environmental
Health Sciences
FX This research received no specific grant from any funding agency in the
public, commercial, or not-for-profit sectors, but was supported in part
by the Intramural Research Program of the National Institutes of Health
(NIH), National Institute of Environmental Health Sciences.
NR 58
TC 6
Z9 6
U1 0
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0961-2033
EI 1477-0962
J9 LUPUS
JI Lupus
PD MAY
PY 2014
VL 23
IS 6
SI SI
BP 527
EP 536
DI 10.1177/0961203313511680
PG 10
WC Rheumatology
SC Rheumatology
GA AF6KU
UT WOS:000334824800004
PM 24763537
ER
PT J
AU Wallace, BC
Laws, MB
Small, K
Wilson, IB
Trikalinos, TA
AF Wallace, Byron C.
Laws, M. Barton
Small, Kevin
Wilson, Ira B.
Trikalinos, Thomas A.
TI Automatically Annotating Topics in Transcripts of Patient-Provider
Interactions via Machine Learning
SO MEDICAL DECISION MAKING
LA English
DT Article
DE machine learning; natural language processing; speech acts;
patient-provider interaction; CRF; communication; informatics
ID OF-THE-LITERATURE; HIV CARE; ADHERENCE; DIALOGUE; UTILITY
AB Background. Annotated patient-provider encounters can provide important insights into clinical communication, ultimately suggesting how it might be improved to effect better health outcomes. But annotating outpatient transcripts with Roter or General Medical Interaction Analysis System (GMIAS) codes is expensive, limiting the scope of such analyses. We propose automatically annotating transcripts of patient-provider interactions with topic codes via machine learning. Methods. We use a conditional random field (CRF) to model utterance topic probabilities. The model accounts for the sequential structure of conversations and the words comprising utterances. We assess predictive performance via 10-fold cross-validation over GMIAS-annotated transcripts of 360 outpatient visits (>230,000 utterances). We then use automated in place of manual annotations to reproduce an analysis of 116 additional visits from a randomized trial that used GMIAS to assess the efficacy of an intervention aimed at improving communication around antiretroviral (ARV) adherence. Results. With respect to 6 topic codes, the CRF achieved a mean pairwise kappa compared with human annotators of 0.49 (range: 0.47-0.53) and a mean overall accuracy of 0.64 (range: 0.62-0.66). With respect to the RCT reanalysis, results using automated annotations agreed with those obtained using manual ones. According to the manual annotations, the median number of ARV-related utterances without and with the intervention was 49.5 versus 76, respectively (paired sign test P = 0.07). When automated annotations were used, the respective numbers were 39 versus 55 (P = 0.04). While moderately accurate, the predicted annotations are far from perfect. Conversational topics are intermediate outcomes, and their utility is still being researched. Conclusions. This foray into automated topic inference suggests that machine learning methods can classify utterances comprising patient-provider interactions into clinically relevant topics with reasonable accuracy.
C1 [Wallace, Byron C.; Laws, M. Barton; Wilson, Ira B.; Trikalinos, Thomas A.] Brown Univ, Dept Hlth Serv Policy & Practice, Sch Publ Hlth, Providence, RI 02903 USA.
[Small, Kevin] NIH, Bethesda, MD 20892 USA.
RP Wallace, BC (reprint author), Brown Univ, Dept Hlth Serv Policy & Practice, 121 South Main St, Providence, RI 02903 USA.
EM byron_wallace@brown.edu
RI Wilson, Ira/F-9190-2016
OI Wilson, Ira/0000-0002-0246-738X
FU National Institute of Mental Health [2 K24MH092242]; [R01MH083595]
FX Received 13 March 2013 from Department of Health Services, Policy and
Practice, Brown University, School of Public Health, Providence, RI
(BCW, MBL, IBW, TAT) and National Institutes of Health, Bethesda, MD
(KS). Financial support for this study was provided in part by the
National Institute of Mental Health (2 K24MH092242). The annotation of
the data used in this work was supported by grant R01MH083595. The
funding agreement ensured the authors' independence in designing the
study, interpreting the data, and writing and publishing the report. The
authors declare no competing interests. Revision accepted for
publication 4 November 2013.
NR 28
TC 4
Z9 4
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD MAY
PY 2014
VL 34
IS 4
BP 503
EP 512
DI 10.1177/0272989X13514777
PG 10
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA AF0JA
UT WOS:000334398900011
PM 24285151
ER
PT J
AU Cizza, G
de Jonge, L
Piaggi, P
Mattingly, M
Zhao, XC
Lucassen, E
Rother, KI
Sumner, AE
Csako, G
AF Cizza, Giovanni
de Jonge, Lilian
Piaggi, Paolo
Mattingly, Megan
Zhao, Xiongce
Lucassen, Eliane
Rother, Kristina I.
Sumner, Anne E.
Csako, Gyorgy
CA NIDDK Sleep Extension Study
TI Neck Circumference Is a Predictor of Metabolic Syndrome and Obstructive
Sleep Apnea in Short-Sleeping Obese Men and Women
SO METABOLIC SYNDROME AND RELATED DISORDERS
LA English
DT Article
ID INSULIN-RESISTANCE; CARDIOVASCULAR RISK; ADULTS; DURATION; QUALITY;
DEPRIVATION; ADIPONECTIN; ADOLESCENTS; EPIDEMIC; DISEASE
AB Background: The constellation of metabolic syndrome, although controversial with regard to its clinical usefulness, is epidemiologically related to increased diabetes risk and cardiovascular mortality. Our goal was to investigate the associations among neck circumference (NC), obstructive sleep apnea syndromes (OSAS), and metabolic syndrome in obese men and women sleeping less than 6.5hr per night. Methods: This was a cross-sectional study of obese men and premenopausal obese women sleeping less than 6.5hr per night. We enrolled 120 individuals (92 women), age 40.56.9 years and body mass index (BMI) 38.66.5kg/m(2). Metabolic syndrome severity was assessed by a score and OSAS was defined as a respiratory disturbance index (RDI) 5. Metabolic end endocrine parameters were measured, and sleep duration was determined by actigraphy and validated questionnaires. Results: Metabolic syndrome was found in 41% and OSAS in 58% (28% had both). Subjects with metabolic syndrome were 3 years older and more often Caucasian; they had higher RDI scores, larger NC, more visceral fat, lower serum adiponectin, higher 24-hr urinary norepinephrine (NE) excretion, and lower growth hormone concentrations. A NC of 38cm had a sensitivity of 54% and 58% and a specificity of 70% and 79% in predicting the presence of metabolic syndrome and OSAS, respectively. RDI, adiponectin, and NC accounted for approximately 30% of the variability in the metabolic syndrome score, as estimated by an age-, gender-, and race-corrected multivariate model (R-2=0.376, P<0.001). Conclusion: Greater NC is associated with OSAS and metabolic syndrome in short-sleeping obese men and premenopausal obese women. Addition of NC to the definition of metabolic syndrome should be considered and needs to be validated in future studies.
C1 [Cizza, Giovanni; de Jonge, Lilian; Mattingly, Megan; Lucassen, Eliane] NIDDK, Sect Neuroendocrinol Obes, DEOB, Bethesda, MD 20892 USA.
[Piaggi, Paolo] Univ Hosp Pisa, Endocrinol Unit, Obes Res Ctr, Pisa, Italy.
[Piaggi, Paolo] NIDDK, Obes & Diabet Clin Res Sect, Phoenix, AZ USA.
[Zhao, Xiongce] NIDDK, Intramural Res Program, Bethesda, MD 20892 USA.
[Lucassen, Eliane] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Neurophysiol Lab, Leiden, Netherlands.
[Rother, Kristina I.] NIDDK, Sect Pediat Diabet & Metab, DEOB, Bethesda, MD 20892 USA.
[Sumner, Anne E.] NIDDK, Ethn & Hlth Sect, DEOB, Bethesda, MD 20892 USA.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Cizza, G (reprint author), NIDDK, Sect Neuroendocrinol Obes, DEOB, CRC, Bldg 10,Room 6-3940, Bethesda, MD 20892 USA.
EM gcizza@gmail.com
OI de Jonge, Lilian/0000-0001-5900-0695; Piaggi, Paolo/0000-0003-2774-9161
FU National Institute of Diabetes and Digestive and Kidney Diseases and
Clinical Center, National Institutes of Health (NIH)
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases and
Clinical Center, National Institutes of Health (NIH). We would like to
thank in alphabetical order the following colleagues for their
scientific advice and critical suggestions in the development and
conduct of the study protocol: Karim Calis, Janet Gershengorn, Gregor
Hasler, Emmanuel Mignot, Susan Redline, Terry Phillips, Nancy Sebring,
Duncan Wallace, and Elizabeth Wright. We would also like to thank
present and past members of the study team: Peter Bailey, Laide Bello,
Meredith Coyle, Paula Marincola, Patrick Michaels, Svetlana Primma,
Angela Ramer, Rebecca Romero, Megan Sabo, Tanner Slayden, Sara Torvik,
Elizabeth Widen, Lydia Williams, and Sam Zuber. We would like to thank
Dr. Alex Ling (NIH CC) for analysis of the computer tomography
measurements. The bioinformatics support of Frank Pierce (Esprit Health)
is gratefully acknowledged. Finally, we are grateful to all of our
enthusiastic study participants.
NR 47
TC 12
Z9 13
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-4196
EI 1557-8518
J9 METAB SYNDR RELAT D
JI Metab. Syndr. Relat. Disord.
PD MAY 1
PY 2014
VL 12
IS 4
BP 231
EP 241
DI 10.1089/met.2013.0093
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AF4II
UT WOS:000334674800006
PM 24571423
ER
PT J
AU Richardson, SP
Beck, S
Bliem, B
Hallett, M
AF Richardson, Sarah Pirio
Beck, Sandra
Bliem, Barbara
Hallett, Mark
TI Abnormal Dorsal Premotor-Motor Inhibition in Writer's Cramp
SO MOVEMENT DISORDERS
LA English
DT Article
DE TMS; dystonia; motor cortex
ID DYSTONIA; CORTEX; MOVEMENT
AB The authors hypothesized that a deficient premotor-motor inhibitory network contributes to the unwanted involuntary movements in dystonia. The authors studied nine controls and nine patients with writer's cramp (WC). Dorsal premotor-motor cortical inhibition (dPMI) was tested by applying conditioning transcranial magnetic stimulation (TMS) to the dorsal premotor cortex and then a test pulse to the ipsilateral motor cortex at an interval of 6 ms. The authors used an H-reflex in flexor carpi radialis paired with TMS over the premotor cortex to assess for spinal cord excitability change. Finally, the authors interrupted a choice reaction time task with TMS over dorsal premotor cortex to assess performance in a nondystonic task. The results showed that WC patients exhibited dPMI at rest (88.5%, the ratio of conditioned to unconditioned test pulse), in contrast to controls, who did not show dPMI (109.6%) (P=0.0198). This difference between patients and controls persisted during contraction (100% vs. 112%) and pen-holding (95.6% vs. 111%). The H-reflex in the arm was not modulated by the premotor cortex stimulation. The WC patients made more errors, and the error rate improved with TMS over the premotor cortex. These results suggest that abnormal premotor-motor interactions may play a role in the pathophysiology of focal dystonia. The dPMI was not modulated by task in either group, but was constantly greater in the patients. The significance of the increased inhibition is likely to be compensatory. It appears to be a robust finding and, in combination with other features, could be further explored as a biomarker. (c) 2014 International Parkinson and Movement Disorder Society
C1 [Richardson, Sarah Pirio] Univ New Mexico, Hlth Sci Ctr, Dept Neurol, Albuquerque, NM 87131 USA.
[Beck, Sandra] Univ Freiburg, Dept Neurol & Clin Neurophysiol, D-79106 Freiburg, Germany.
[Richardson, Sarah Pirio; Beck, Sandra; Bliem, Barbara; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD USA.
RP Richardson, SP (reprint author), 1 Univ New Mexico, Dept Neurol, Hlth Sci Ctr, MSC 10 5620, Albuquerque, NM 87131 USA.
EM spiriorichardson@salud.unm.edu
FU National Center for Research Resources; National Center for Advancing
Translational Sciences of the National Institutes of Health [KL2
TR000089, UL1 TR000041]; NIH/NINDS
FX This study was supported (in part or in full) by the National Center for
Research Resources and the National Center for Advancing Translational
Sciences of the National Institutes of Health through Grant Number KL2
TR000089 and Grant Number UL1 TR000041. The project was also supported
through NIH/NINDS Intramural Funds. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH.
NR 14
TC 3
Z9 3
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAY
PY 2014
VL 29
IS 6
BP 797
EP 803
DI 10.1002/mds.25878
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA AG4BI
UT WOS:000335363300015
ER
PT J
AU Miyazaki, Y
Shimizu, A
Ichikawa, I
Hosoya, T
Pastan, I
Matsusaka, T
AF Miyazaki, Yoichi
Shimizu, Akihiro
Ichikawa, Iekuni
Hosoya, Tatsuo
Pastan, Ira
Matsusaka, Taiji
TI Mice are unable to endogenously regenerate podocytes during the repair
of immunotoxin-induced glomerular injury
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE chronic renal failure; glomerulosclerosis; mouse model; podocyte;
regeneration
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; PARIETAL EPITHELIAL-CELLS; RENAL
PROGENITORS; MOUSE MODEL; CONTRIBUTE; DISEASE; EXPRESSION; SCLEROSIS;
TURNOVER; BIOLOGY
AB The average body size of mankind has continuously increased with improving health and nutrition since about 250 years (average height used to be about 15 cm smaller). It can be speculated that our podocyte endowment may no longer be sufficient to handle the increase in body size (especially in males).Recent studies have reported that podocytes are postnatally generated from progenitor cells localized in Bowman's capsule or in the bone marrow. In the present study, we investigated whether or not podocyte regeneration is important in the repair of injured glomeruli after mild podocyte injury in mice.
Mild podocyte injury was induced in NEP25 mice (n = 8) by injecting an immunotoxin, LMB2 (0.625 ng/g body weight). Control mice, not injured by LMB2 injection (n = 7) was used as a comparison. Proliferating cells were labeled by continuous infusion of bromodeoxyuridine (BrdU). Podocytes, identified by nephrin, WT1 or podocin staining, that had incorporated BrdU were enumerated 4 weeks later.
A total of 742 corpuscles were inspected in serial sections stained for BrdU and nephrin; 19% showed sclerosis. BrdU(+) cells were observed in both the glomeruli and Bowman's capsules, averaging 2.5 +/- 3.1 in non-sclerotic corpuscles and 7.0 +/- 5.8 in sclerotic corpuscles. Only one BrdU(+) cell was also positive for nephrin. Another cell, localized at a position consistent with its potential identification as a podocyte, was nephrin negative but had incorporated BrdU. WT1 staining similarly revealed that only two nuclei were doubly positive for BrdU and WT1. Additional 1676 corpuscles were inspected by double staining for BrdU and podocin; none were doubly positive.
Podocytes are not replenished by proliferation of endogenous progenitor cells in mice with glomerular injury.
C1 [Miyazaki, Yoichi; Shimizu, Akihiro; Hosoya, Tatsuo] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan.
[Shimizu, Akihiro; Matsusaka, Taiji] Tokai Univ, Sch Med, Dept Internal Med, Isehara, Kanagawa 25911, Japan.
[Ichikawa, Iekuni] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan.
[Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 25911, Japan.
RP Miyazaki, Y (reprint author), Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan.
EM yoichimiyazaki@jikei.ac.jp
FU Japan Society for the Promotion of Science, MEXT, HAITEKU; NIH, Center
for Cancer Research at the National Cancer Institute
FX We thank Ms Shiho Imai and Ms Chie Sakurai for technical assistance.
This study was supported by a Grant-in Aid for Scientific Research from
the Japan Society for the Promotion of Science, MEXT, HAITEKU and in
part by the Intramural Research Program of the NIH, Center for Cancer
Research at the National Cancer Institute. The results presented in this
paper have not been published previously.
NR 23
TC 6
Z9 6
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
EI 1460-2385
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD MAY
PY 2014
VL 29
IS 5
BP 1005
EP 1012
DI 10.1093/ndt/gft413
PG 8
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA AH4JT
UT WOS:000336093900013
PM 24322577
ER
PT J
AU Huizing, M
Carrillo-Carrasco, N
Malicdan, MCV
Noguchi, S
Gahl, WA
Mitrani-Rosenbaum, S
Argov, Z
Nishino, I
AF Huizing, Marjan
Carrillo-Carrasco, Nuria
Malicdan, May Christine V.
Noguchi, Satoru
Gahl, William A.
Mitrani-Rosenbaum, Stella
Argov, Zohar
Nishino, Ichizo
TI GNE myopathy: New name and new mutation nomenclature
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Distal Myopathy with Rimmed Vacuoles (DMRV); Hereditary Inclusion Body
Myopathy (HIBM); Inclusion Body Myopathy 2 (IBM2); Nonaka myopathy;
Sialic acid; UDP-GlcNAc 2-epimersa/ManNAc kinase; GNE Myopathy
ID INCLUSION-BODY MYOPATHY; DISTAL MYOPATHY; RIMMED VACUOLES; KINASE; MAPS;
GENE
C1 [Huizing, Marjan; Malicdan, May Christine V.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Carrillo-Carrasco, Nuria] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA.
[Noguchi, Satoru; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Tokyo, Japan.
[Mitrani-Rosenbaum, Stella] Hadassah Hebrew Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel.
[Argov, Zohar] Hadassah Hebrew Univ, Med Ctr, Dept Neurol, Jerusalem, Israel.
RP Huizing, M (reprint author), NHGRI, NIH, 10 Ctr Dr,Bid 10,Rm 10C103, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
RI Carrillo-Carrasco, Nuria/B-9034-2009;
OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808; Nishino,
Ichizo/0000-0001-9452-112X
FU Intramural NIH HHS [ZIA HG200322-09]
NR 8
TC 14
Z9 14
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
EI 1873-2364
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD MAY
PY 2014
VL 24
IS 5
BP 387
EP 389
DI 10.1016/j.nmd.2014.03.004
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH7XT
UT WOS:000336349400003
PM 24685570
ER
PT J
AU Bertrand, AT
Bonnemann, CG
Bonne, G
AF Bertrand, Anne T.
Boennemann, Carsten G.
Bonne, Gisele
CA FHL1 Myopathy Consortium
TI 199th ENMC international workshop: FHL1 related myopathies, June 7-9,
2013, Naarden, The Netherlands
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
ID REDUCING-BODY MYOPATHY; RIGID SPINE SYNDROME; LIM DOMAIN MUTATION;
BINDING-PROTEIN-C; HYPERTROPHIC CARDIOMYOPATHY; CYTOPLASMIC BODIES; 1
GENE; IDENTIFICATION; MYOFIBRILLAR; COMPONENTS
C1 [Bertrand, Anne T.; Bonne, Gisele] INSERM, U974, F-75013 Paris, France.
[Bertrand, Anne T.; Bonne, Gisele] Univ Paris 06, Sorbonne Univ, Inserm U974, Myol Ctr Rech,CNRS,Inst Myol, F-75651 Paris, France.
[Boennemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA.
[Bonne, Gisele] Grp Hosp Pitie Salpetriere, AP HP, UE Cardiogenet & Myogenet Mol, Serv Biochim Metabol, F-75013 Paris, France.
RP Bonne, G (reprint author), Univ Paris 06, Sorbonne Univ, Inserm U974, Myol Ctr Rech,CNRS,Inst Myol, UM76,FRE3617,GH Pitie Salpetriere47, F-75651 Paris, France.
EM g.bonne@institut-myologie.org
RI Bonne, Gisele/G-3121-2013;
OI Mitchell, Christina A/0000-0001-9372-3192
FU European Neuromuscular Centre (ENMC); Association Francaise contre les
Myopathies (France); Deutsche Gesellschaft fur Muskelkranke (Germany);
Muscular Dystrophy Campain (UK); Muskelvindfonden (Denmark); Prinses
Beatrix Spierfonds (the Netherlands); Schweizerische Stiftung fur die
Erforschung der Muskelkrankheiten (Switzerland); Telethon Foundation
(Italy); Spierziekten Nederland (The Netherlands)
FX This workshop was made possible thanks to the financial support of the
European Neuromuscular Centre (ENMC) and ENMC main Sponsors: Association
Francaise contre les Myopathies (France), Deutsche Gesellschaft fur
Muskelkranke (Germany), Muscular Dystrophy Campain (UK),
Muskelvindfonden (Denmark), Prinses Beatrix Spierfonds (the
Netherlands), Schweizerische Stiftung fur die Erforschung der
Muskelkrankheiten (Switzerland), Telethon Foundation (Italy),
Spierziekten Nederland (The Netherlands), and Associated members:
Finnish Neuromuscular Association (Finland).
NR 32
TC 2
Z9 2
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
EI 1873-2364
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD MAY
PY 2014
VL 24
IS 5
BP 453
EP 462
DI 10.1016/j.nmd.2014.02.002
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AH7XT
UT WOS:000336349400014
PM 24613424
ER
PT J
AU Wang, XY
Chrysovergis, K
Kosak, J
Eling, TE
AF Wang, Xingya
Chrysovergis, Kali
Kosak, Justin
Eling, Thomas E.
TI Lower NLRP3 Inflammasome Activity in NAG-1 Transgenic Mice Is Linked to
a Resistance to Obesity and Increased Insulin Sensitivity
SO OBESITY
LA English
DT Article
ID MACROPHAGE INHIBITORY CYTOKINE-1; ADIPOSE-TISSUE; CASPASE-1 ACTIVATION;
ADIPOCYTES; EXPRESSION; DIFFERENTIATION; INTERLEUKIN-18; ADIPONECTIN;
NAG-1/GDF15; DEFICIENCY
AB Objective: The NLRP3 inflammasome plays an important regulatory role in obesity-induced insulin resistance. NSAID activated gene-1 (NAG-1) is a divergent member of the TGF-beta superfamily. NAG-1 Tg mice are resistant to dietary- and genetic-induced obesity and have improved insulin sensitivity. The objective was to examine whether NLRP3 inflammasome activity is associated with this observed phenotype in NAG-1 Tg mice.
Methods: Key components of the NLRP3 inflammasome were examined in NAG-1 Tg mice on both regular and high fat diet (HFD) conditions.
Results: The expression of caspase-1 and ASC, key components of the NLRP3 inflammasome, is significantly reduced at mRNA and protein levels in white adipose tissue (WAT) of NAG-1 Tg mice. HFD increases the expression of caspase-1 and ASC in WT mice, but their expression is reduced in NAG-1 Tg mice. Furthermore, there is reduced IL-18, IL-1 beta, and TNF-alpha expression in the WAT of NAG-1 Tg mice. NAG-1 Tg mice have significantly lower serum leptin and insulin levels and reduced expression of macrophage infiltration markers (F4/80, CD11b, and CD11c) in WAT.
Conclusions: The study suggests the lower NLRP3 inflammasome activity may play a role in the resistance of NAG-1 Tg mice to diet-induced obesity and improved insulin sensitivity.
C1 [Wang, Xingya; Chrysovergis, Kali; Kosak, Justin; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM eling@niehs.nih.gov
FU NIH; NIEHS Intramural Research Program (Eling) [Z01-ES010016-14]
FX This research was supported by NIH, NIEHS Intramural Research Program
(Eling) Z01-ES010016-14.
NR 34
TC 4
Z9 4
U1 1
U2 6
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 MAY
PY 2014
VL 22
IS 5
BP 1256
EP 1263
DI 10.1002/oby.20638
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AH3OR
UT WOS:000336034400034
PM 24124102
ER
PT J
AU Wing, MR
Yang, W
Teal, V
Navaneethan, S
Tao, KX
Ojo, A
Guzman, NN
Reilly, M
Wolman, M
Rosas, SE
Cuevas, M
Fischer, M
Lustigova, E
Master, SR
Xie, DW
Appleby, D
Joffe, M
Kusek, J
Feldman, HI
Raj, DS
AF Wing, Maria R.
Yang, Wei
Teal, Valerie
Navaneethan, Sankar
Tao, Kaixiang
Ojo, Akinlolu
Guzman, Nicolas N.
Reilly, Muredach
Wolman, Melanie
Rosas, Sylvia E.
Cuevas, Magda
Fischer, Michael
Lustigova, Eva
Master, Stephen R.
Xie, Dawei
Appleby, Dina
Joffe, Marshall
Kusek, John
Feldman, Harold I.
Raj, Dominic S.
CA Chronic Renal Insufficiency Cohort
TI Race Modifies the Association Between Adiposity and Inflammation in
Patients with Chronic Kidney Disease: Findings from the Chronic Renal
Insufficiency Cohort Study
SO OBESITY
LA English
DT Article
ID BIOELECTRICAL-IMPEDANCE ANALYSIS; BODY-MASS INDEX; SKELETAL-MUSCLE;
HEMODIALYSIS-PATIENTS; INTERLEUKIN-6; OBESITY; ADULTS; FAT; POPULATION;
RELEASE
AB Objective: The race-specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined.
Methods: Plasma concentration of interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, tumor necrosis factor (TNF)-alpha, TGF-beta, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin was measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Bioelectric impedance analysis was used to determine body fat mass (BFM) and fat-free mass (FFM).
Results: Plasma levels of hs-CRP, fibrinogen, IL-1RA, IL-6, and TNF-alpha increased and serum albumin decreased across the quartiles of body mass index. In multivariable analysis, BFM and FFM were positively associated with hs-CRP, fibrinogen, IL-1 beta, IL-1RA, and IL-6. One standard deviation (SD) increase in BFM and FFM was associated with 0.36 (95% confidence interval [CI] 50.33, 0.39) and 0.26 (95% CI = 0.22, 0.30) SD increase in log-transformed hs-CRP, respectively (P < 0.001). Race stratified analysis showed that the association between biomarkers and BFM and FFM differed by race, with Caucasians, demonstrating a stronger association with markers of inflammation than African Americans.
Conclusions: BFA and FFM are positively associated with markers of inflammation in patients with CKD. Race stratified analysis showed that Caucasians have a stronger association with markers of inflammation compared to African Americans.
C1 [Wing, Maria R.; Guzman, Nicolas N.; Raj, Dominic S.] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20052 USA.
[Yang, Wei; Teal, Valerie; Tao, Kaixiang; Xie, Dawei; Appleby, Dina; Joffe, Marshall] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Navaneethan, Sankar] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA.
[Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA.
[Cuevas, Magda] Univ Penn, Med Ctr, Dept Med, Philadelphia, PA 19104 USA.
[Rosas, Sylvia E.] Univ Penn, Perelman Sch Med, Renal Elect & Hypertens Div, Philadelphia, PA 19104 USA.
[Fischer, Michael] Univ Illinois, Med Ctr, Jesse Brown VA Med Ctr, Dept Med, Chicago, IL USA.
[Lustigova, Eva] Tulane Univ, Dept Epidemiol, New Orleans, LA USA.
[Master, Stephen R.] Univ Pennsylvania Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA USA.
[Kusek, John] Natl Inst Diabet & Digest & Kidney Dis, Div Kidney Urol & Hematol Dis, Bethesda, MD USA.
[Feldman, Harold I.] Univ Penn, Perelman Sch Med, Clin Epidemiol Unit, Philadelphia, PA USA.
RP Raj, DS (reprint author), George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20052 USA.
EM draj@mfa.gwu.edu
OI Teal, Valerie/0000-0001-7116-5353
FU National Institute of Diabetes and Digestive and Kidney Diseases
[5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021, 5U01DK061028,
5U01DK60980, 5U01DK060963, 5U01DK060902]; National Institutes of Health
[UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042,
UL1RR024986, UL1RR029879, RR05096, UL1RR024131]; [R01 DK073665-01A1]
FX This study was sponsored by R01 DK073665-01A1, The National Institute of
Diabetes and Digestive and Kidney Diseases (5U01DK060990, 5U01DK060984,
5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963,
5U01DK060902), and The National Institutes of Health (UL1RR024134,
UL1RR025005, M01RR16500, UL1RR024989, M01RR000042, UL1RR024986,
UL1RR029879, RR05096, UL1RR024131).
NR 35
TC 4
Z9 6
U1 0
U2 0
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 MAY
PY 2014
VL 22
IS 5
BP 1359
EP 1366
DI 10.1002/oby.20692
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AH3OR
UT WOS:000336034400047
PM 24415732
ER
PT J
AU Green, AK
Jacques, PF
Rogers, G
Fox, CS
Meigs, JB
McKeown, NM
AF Green, Angela K.
Jacques, Paul F.
Rogers, Gail
Fox, Caroline S.
Meigs, James B.
McKeown, Nicola M.
TI Sugar-Sweetened Beverages and Prevalence of the Metabolically Abnormal
Phenotype in the Framingham Heart Study
SO OBESITY
LA English
DT Article
ID FOOD-FREQUENCY QUESTIONNAIRE; INSULIN-RESISTANCE; HEALTHY OBESE;
CARDIOVASCULAR-DISEASE; NORMAL-WEIGHT; AGED ADULTS; US ADULTS; RISK;
CONSUMPTION; REPRODUCIBILITY
AB Objective: The purpose of this study was to examine the relationship between usual sugar-sweetened beverage (SSB) consumption and prevalence of abnormal metabolic health across body mass index (BMI) categories.
Methods: The metabolic health of 6,842 non-diabetic adults was classified using cross-sectional data from the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. Adults were classified as normal weight, overweight or obese and, within these categories, metabolic health was defined based on five criteria-hypertension, elevated fasting glucose, elevated triglycerides, low HDL cholesterol, and insulin resistance. Individuals without metabolic abnormalities were considered metabolically healthy. Logistic regression was used to examine the associations between categories of SSB consumption and risk of metabolic health after stratification by BMI.
Results: Comparing the highest category of SSB consumers (median of 7 SSB per week) to the lowest category (non-consumers), odds ratios (95% confidence intervals) for metabolically abnormal phenotypes, compared to the metabolically normal, were 1.9 (1.1-3.4) among the obese, 2.0 (1.4-2.9) among the overweight, and 1.9 (1.4-2.6) among the normal weight individuals.
Conclusions: In this cross-sectional analysis, it is observed that, irrespective of weight status, consumers of SSB were more likely to display metabolic abnormalities compared to non-consumers in a dosedependent manner.
C1 [Green, Angela K.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Jacques, Paul F.; Rogers, Gail; McKeown, Nicola M.] Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Jacques, Paul F.; McKeown, Nicola M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Dept Med, Boston, MA 02115 USA.
[Fox, Caroline S.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA.
RP McKeown, NM (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
EM nicola.mckeown@tufts.edu
FU National Heart Lung and Blood Institute [NO1-HC-25195]; USDA
Agricultural Research Service [58-1950-0-014]
FX This study was supported by grants from the National Heart Lung and
Blood Institute (contract NO1-HC-25195) and the USDA Agricultural
Research Service (agreement 58-1950-0-014). The funding providers did
not play a role in any aspect of this study.
NR 36
TC 4
Z9 4
U1 0
U2 2
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 MAY
PY 2014
VL 22
IS 5
BP E157
EP E163
DI 10.1002/oby.20724
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AH3OR
UT WOS:000336034400024
PM 24550031
ER
PT J
AU Aschebrook-Kilfoy, B
Ward, MH
Della Valle, CT
Friesen, MC
AF Aschebrook-Kilfoy, Briseis
Ward, Mary H.
Della Valle, Curt T.
Friesen, Melissa C.
TI Occupation and thyroid cancer
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Review
ID SERUM THYROTROPIN CONCENTRATION; IONIZING-RADIATION EXPOSURE; BRITISH
NUCLEAR-FUELS; AGRICULTURAL HEALTH; ENVIRONMENTAL CHEMICALS; PESTICIDE
APPLICATORS; HUMAN CARCINOGENS; DISRUPTING CHEMICALS; INCREASING
INCIDENCE; PAPILLARY CANCER
AB Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text occupation' job' employment' or work' and thyroid cancer'. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design and exposure assessment approach. Where available, gender-stratified results are reported. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis.
C1 [Aschebrook-Kilfoy, Briseis] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Ward, Mary H.; Della Valle, Curt T.; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD USA.
RP Aschebrook-Kilfoy, B (reprint author), Univ Chicago, Dept Hlth Studies, 5841 South Maryland Ave,N101B, Chicago, IL 60637 USA.
EM brisa@uchicago.edu
RI Friesen, Melissa/A-5362-2009
FU Intramural Research Program of the National Cancer Institute (NCI), NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute (NCI), NIH.
NR 98
TC 9
Z9 10
U1 2
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
EI 1470-7926
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD MAY
PY 2014
VL 71
IS 5
BP 366
EP 380
DI 10.1136/oemed-2013-101929
PG 15
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AF0IM
UT WOS:000334397500012
PM 24604144
ER
PT J
AU Kurmasheva, RT
Reynolds, CP
Kang, MH
Allievi, C
Houghton, PJ
Smith, MA
AF Kurmasheva, Raushan T.
Reynolds, C. Patrick
Kang, Min H.
Allievi, Cecilia
Houghton, Peter J.
Smith, Malcolm A.
TI Initial Testing (Stage 1) of the Topoisomerase II Inhibitor Pixantrone,
by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; topoisomerase 2
inhibitor
ID AZA-ANTHRACENEDIONE; PHASE-I; BBR-2778; DNA; CYTOTOXICITY; MICE;
MITOXANTRONE; FORMALDEHYDE; NEPHROPATHY; DOXORUBICIN
AB Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0nM to 30.0M) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5mg/kg) administered intravenously using an every 4 dayx3 schedule. In vitro pixantrone showed a median relative IC50 value of 54nM (range <3nM to 1.03M). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft. Pediatr Blood Cancer 2014;61:922-924. (c) 2013 Wiley Periodicals, Inc.
C1 [Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH 43205 USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Allievi, Cecilia] Cell Therapeut, Monza, Italy.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kurmasheva, RT (reprint author), Nationwide Childrens Hosp, Ctr Childhood Canc, 700 Childrens Dr, Columbus, OH 43205 USA.
EM raushan.kurmasheva@nationwidechildrens.org
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CA21765.
NR 18
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2014
VL 61
IS 5
BP 922
EP 924
DI 10.1002/pbc.24800
PG 3
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AD7ZI
UT WOS:000333485600028
PM 24166988
ER
PT J
AU Akshintala, S
Dombi, E
Baldwin, A
Gillespie, A
Goodspeed, W
Goodwin, A
Whitcomb, P
Steinberg, S
Widemann, B
AF Akshintala, Srivandana
Dombi, Eva
Baldwin, Andrea
Gillespie, Andy
Goodspeed, Wendy
Goodwin, Anne
Whitcomb, Patricia
Steinberg, Seth
Widemann, Brigitte
TI PREDICTORS OF PLEXIFORM NEUROFIBROMA (PN) GROWTH IN PATIENTS WITH
NEUROFIBROMATOSIS 1 (NF1)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Akshintala, Srivandana; Dombi, Eva; Baldwin, Andrea; Gillespie, Andy; Goodspeed, Wendy; Goodwin, Anne; Whitcomb, Patricia; Steinberg, Seth; Widemann, Brigitte] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2014
VL 61
SU 1
SI SI
BP S32
EP S33
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AG5WT
UT WOS:000335490100114
ER
PT J
AU Rao, VK
Rosenberg, P
Price, S
Gill, F
Pittaluga, S
Fleisher, T
Lenardo, M
Jaffe, E
AF Rao, V. Koneti
Rosenberg, Philip
Price, Susan
Gill, Fred
Pittaluga, Stefania
Fleisher, Thomas
Lenardo, Michael
Jaffe, Elaine
TI ENHANCED RISK OF LYMPHOMA IN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME
(ALPS) DUE TO FAS MUTATIONS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Rao, V. Koneti; Rosenberg, Philip; Price, Susan; Gill, Fred; Pittaluga, Stefania; Fleisher, Thomas; Lenardo, Michael; Jaffe, Elaine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2014
VL 61
SU 1
SI SI
BP S82
EP S82
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AG5WT
UT WOS:000335490100285
ER
PT J
AU Brown, RJ
Yanovski, JA
AF Brown, Rebecca J.
Yanovski, Jack A.
TI Estimation of insulin sensitivity in children: methods, measures and
controversies
SO PEDIATRIC DIABETES
LA English
DT Review
DE FSIGT; glucose clamp technique; glucose tolerance; HOMA; insulin
sensitivity; QUICKI; surrogate measures
ID GLUCOSE-TOLERANCE TEST; BETA-CELL FUNCTION; DEPENDENT DIABETES-MELLITUS;
OBESE ADOLESCENT BOYS; MINIMAL MODEL; INTRAVENOUS GLUCOSE; OVERWEIGHT
CHILDREN; AFRICAN-AMERICAN; FATTY-ACID; IN-VIVO
AB Insulin resistance is defined as a state where insulin produces a diminished biological response, primarily in its capacity as a glucose-regulating hormone. Insulin resistance is commonly diagnosed by pediatric clinicians, but is rarely measured directly in children or adolescents. This review provides an overview of the techniques that can be used to assess insulin sensitivity in children, summarizing the methods involved, the assumptions, pitfalls, and appropriate uses of each technique, as well as their validation and reproducibility in pediatric samples.
C1 [Brown, Rebecca J.] NIDDK, Diabet Endocrinol & Obes Branch, Bethesda, MD 20892 USA.
[Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 10 Ctr Dive,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU NICHD, NIH; NIDDK, NIH
FX The authors are supported by the Intramural Research Programs of NICHD,
NIH, and NIDDK, NIH. J. A. Y. is a Commissioned Officer in the US Public
Health Service, Department of Health and Human Services. The opinions
and assertions expressed herein are those of the authors and are not to
be construed as reflecting the views of the US Public Health Service,
the National Institutes of Health, or the US Department of Health and
Human Services.
NR 72
TC 10
Z9 10
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1399-543X
EI 1399-5448
J9 PEDIATR DIABETES
JI Pediatr. Diabetes
PD MAY
PY 2014
VL 15
IS 3
BP 151
EP 161
DI 10.1111/pedi.12146
PG 11
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA AH0UL
UT WOS:000335836000002
PM 24754463
ER
PT J
AU Cabana, MD
Cheng, TL
Bauer, AJ
Bogue, CW
Chien, AT
Dean, JM
Scheindlin, B
Kelle, A
Coyne-Beasley, T
DiMeglio, L
DeGraw, CA
Dougherty, D
Freed, GL
Guttmacher, AE
Minkovitz, C
Shalowitz, M
Cull, W
AF Cabana, Michael D.
Cheng, Tina L.
Bauer, Andrew J.
Bogue, Clifford W.
Chien, Alyna T.
Dean, J. Michael
Scheindlin, Ben
Kelle, Angela
Coyne-Beasley, Tamera
DiMeglio, Linda
DeGraw, Christopher A.
Dougherty, Denise
Freed, Gary L.
Guttmacher, Alan E.
Minkovitz, Cynthia
Shalowitz, Madeleine
Cull, William
CA Comm Pediat Res
TI Promoting Education, Mentorship, and Support for Pediatric Research
SO PEDIATRICS
LA English
DT Article
DE pediatric education; training; workforce; epidemiology; health services
research; community-based participatory research; translational
research; basic science research; postgraduate training
ID CLINICAL-RESEARCH; TRANSLATIONAL RESEARCH; PHYSICIAN-SCIENTISTS;
CAREER-DEVELOPMENT; HEALTH; PROGRAM; CHALLENGES; PERSPECTIVES;
INSTITUTES; MEDICINE
AB Pediatricians play a key role in advancing child health research to best attain and improve the physical, mental, and social health and well-being of all infants, children, adolescents, and young adults. Child health presents unique issues that require investigators who specialize in pediatric research. In addition, the scope of the pediatric research enterprise is transdisciplinary and includes the full spectrum of basic science, translational, community-based, health services, and child health policy research. Although most pediatricians do not directly engage in research, knowledge of research methodologies and approaches promotes critical evaluation of scientific literature, the practice of evidence-based medicine, and advocacy for evidence-based child health policy. This statement includes specific recommendations to promote further research education and support at all levels of pediatric training, from premedical to continuing medical education, as well as recommendations to increase support and mentorship for research activities. Pediatric research is crucial to the American Academy of Pediatrics' goal of improving the health of all children. The American Academy of Pediatrics continues to promote and encourage efforts to facilitate the creation of new knowledge and ways to reduce barriers experienced by trainees, practitioners, and academic faculty pursuing research.
C1 [DeGraw, Christopher A.] Maternal & Child Hlth Bur, Rockville, MD USA.
[Dougherty, Denise] Agcy Healthcare Res & Qual, Rockville, MD USA.
[Guttmacher, Alan E.] NICHHD, Rockville, MD USA.
OI Kelle, Angela/0000-0002-5222-0916; DiMeglio, Linda/0000-0002-8033-6078
NR 50
TC 3
Z9 3
U1 1
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAY
PY 2014
VL 133
IS 5
BP 943
EP 949
DI 10.1542/peds.2014-0448
PG 7
WC Pediatrics
SC Pediatrics
GA AG2HK
UT WOS:000335236800026
ER
PT J
AU Suren, P
Gunnes, N
Roth, C
Bresnahan, M
Hornig, M
Hirtz, D
Lie, KK
Lipkin, WI
Magnus, P
Reichborn-Kjennerud, T
Schjolberg, S
Susser, E
Oyen, AS
Smith, GD
Stoltenberg, C
AF Suren, Pal
Gunnes, Nina
Roth, Christine
Bresnahan, Michaeline
Hornig, Mady
Hirtz, Deborah
Lie, Kari Kveim
Lipkin, W. Ian
Magnus, Per
Reichborn-Kjennerud, Ted
Schjolberg, Synnve
Susser, Ezra
Oyen, Anne-Siri
Smith, George Davey
Stoltenberg, Camilla
TI Parental Obesity and Risk of Autism Spectrum Disorder
SO PEDIATRICS
LA English
DT Article
DE autism spectrum disorder; autistic disorder; Asperger disorder; PDD-NOS;
parental obesity; parental BMI; child cohort study
ID BODY-MASS INDEX; BIRTH COHORT; BIAS; PREGNANCY; DELETIONS; ORIGIN; ADHD
AB OBJECTIVES:The objective of the study was to investigate the associations among maternal prepregnancy BMI, paternal BMI, and the risk of autism spectrum disorders (ASDs) in children.METHODS:The study sample of 92909 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study. The age range was 4.0 through 13.1 (mean 7.4) years. Relative risks of ASDs were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models.RESULTS:At the end of follow-up on December 31, 2012, 419 children in the study sample had been diagnosed with ASDs: 162 with autistic disorder, 103 with Asperger disorder, and 154 with pervasive developmental disorder not otherwise specified. Maternal obesity (BMI 30) was only weakly associated with ASD risk, whereas paternal obesity was associated with an increased risk of autistic disorder and Asperger disorder. The risk of autistic disorder was 0.27% (25 of 9267) in children of obese fathers and 0.14% (59 of 41603) in children of fathers with normal weight (BMI <25), generating an adjusted OR of 1.73 (95% CI: 1.07-2.82). For Asperger disorder, analyses were limited to children aged 7 years (n = 50116). The risk was 0.38% (18 of 4761) in children of obese fathers and 0.18% (42 of 22736) in children of normal-weight fathers, and the adjusted OR was 2.01 (95% CI: 1.13-3.57). No associations were found for pervasive developmental disorder not otherwise specified.CONCLUSIONS:Paternal obesity is an independent risk factor for ASDs in children. The associations should be investigated further in genetic and epigenetic studies.
C1 [Suren, Pal; Gunnes, Nina; Roth, Christine; Lie, Kari Kveim; Magnus, Per; Reichborn-Kjennerud, Ted; Schjolberg, Synnve; Oyen, Anne-Siri; Stoltenberg, Camilla] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway.
[Suren, Pal] UCL Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England.
[Gunnes, Nina; Roth, Christine; Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Bresnahan, Michaeline; Susser, Ezra] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA.
[Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, Oslo, Norway.
[Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway.
[Smith, George Davey] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England.
[Stoltenberg, Camilla] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
RP Suren, P (reprint author), Norwegian Inst Publ Hlth, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM pal.suren@fhi.no
RI Davey Smith, George/A-7407-2013
OI Davey Smith, George/0000-0002-1407-8314
FU Medical Research Council [MC_UU_12013/1]; NIEHS NIH HHS [N0-ES-75558,
N01ES75558]; NINDS NIH HHS [NS47537, U01 NS047537]
NR 31
TC 26
Z9 28
U1 2
U2 25
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD MAY
PY 2014
VL 133
IS 5
BP E1128
EP E1138
DI 10.1542/peds.2013-3664
PG 11
WC Pediatrics
SC Pediatrics
GA AG2HK
UT WOS:000335236800031
PM 24709932
ER
PT J
AU Chung, CC
Hsing, AW
Yeboah, E
Biritwum, R
Tettey, Y
Adjei, A
Cook, MB
De Marzo, A
Netto, G
Tay, E
Boland, JF
Yeager, M
Chanock, SJ
AF Chung, Charles C.
Hsing, Ann W.
Yeboah, Edward
Biritwum, Richard
Tettey, Yao
Adjei, Andrew
Cook, Michael B.
De Marzo, Angelo
Netto, George
Tay, Evelyn
Boland, Joseph F.
Yeager, Meredith
Chanock, Stephen J.
TI A comprehensive resequence-analysis of 250 kb region of 8q24.21 in men
of African ancestry
SO PROSTATE
LA English
DT Article
DE 8q24.21; genetics; prostate cancer
ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER SUSCEPTIBILITY; LONG-RANGE
INTERACTION; COLORECTAL-CANCER; RISK LOCI; SNP RS6983267; MYC ENHANCER;
IDENTIFIES 5; IN-VIVO; VARIANTS
AB BACKGROUND Genome-wide association studies (GWAS) have identified that a similar to 1 M region centromeric to the MYC oncogene on chromosome 8q24.21 harbors at least five independent loci associated with prostate cancer risk and additional loci associated with cancers of breast, colon, bladder, and chronic lymphocytic leukemia (CLL). Because GWAS identify genetic markers that may be indirectly associated with disease, fine-mapping based on sequence analysis provides important insights into patterns of linkage disequilibrium (LD) and is critical in defining the optimal variants to nominate for biological follow-up. METHODS To catalog variation in individuals of African ancestry, we resequenced a region (250 kb; chr8:128,050,768-128,300,801, hg19) containing several prostate cancer susceptibility loci as well as a locus associated with CLL. Our samples included 78 individuals from Ghana and 47 of African-Americans from Johns Hopkins University. RESULTS After quality control metrics were applied to next-generation sequence data, 1,838 SNPs were identified. Of these, 285 were novel and not yet reported in any public database. Using genotypes derived from sequencing, we refined the LD and recombination hotspots within the region and determined a set of tag SNPs to be used in future fine-mapping studies. Based on LD, we annotated putative risk loci and their surrogates using ENCODE data, which should help guide laboratory studies. CONCLUSIONS In comparison to the 1000 Genome Project data, we have identified additional variants that could be important in establishing priorities for future functional work designed to explain the biological basis of associations between SNPs and both prostate cancer and CLL. Prostate 74:579-589, 2014. (c) 2014 Wiley Periodicals, Inc.
C1 [Chung, Charles C.; Hsing, Ann W.; Cook, Michael B.; Boland, Joseph F.; Yeager, Meredith; Chanock, Stephen J.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chung, Charles C.; Boland, Joseph F.; Yeager, Meredith] SAIC Frederick Inc, Canc Gen Res Lab, Frederick, MD USA.
[Chung, Charles C.; Boland, Joseph F.; Yeager, Meredith] Frederick Natl Lab Canc Res, Frederick, MD USA.
[Yeboah, Edward] Univ Ghana, Dept Urol, Accra, Ghana.
[Biritwum, Richard] Univ Ghana, Dept Epidemiol, Accra, Ghana.
[Tettey, Yao; Adjei, Andrew] Univ Ghana, Dept Pathol, Accra, Ghana.
[De Marzo, Angelo; Netto, George] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Tay, Evelyn] Korle BuTeaching Hosp, Accra, Ghana.
[Tay, Evelyn] Univ Ghana, Sch Med, Accra, Ghana.
RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Adv Technol Center NCI, 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
RI Cook, Michael/A-5641-2009
OI Cook, Michael/0000-0002-0533-7302
FU Intramural NIH HHS [ZIA CP010201-01, Z01 CP010178-06]
NR 45
TC 4
Z9 4
U1 1
U2 19
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 MAY
PY 2014
VL 74
IS 6
BP 579
EP 589
DI 10.1002/pros.22726
PG 11
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA AD7LN
UT WOS:000333445500002
PM 24783269
ER
PT J
AU Huang, T
Li, J
Byrd, RA
AF Huang, Tao
Li, Jess
Byrd, R. Andrew
TI Solution structure of lysine-free (K0) ubiquitin
SO PROTEIN SCIENCE
LA English
DT Article
DE ubiquitin; K0-Ub; NMR; CS-Rosetta
ID NMR CHEMICAL-SHIFTS; LIQUID-CRYSTALLINE PHASE; HYDROPHOBIC CORE;
PROTEIN-STRUCTURE; DIUBIQUITIN; DYNAMICS; UBIQUITYLATION; RECOGNITION;
COUPLINGS; ALIGNMENT
AB Lysine-free ubiquitin (K0-Ub) is commonly used to study the ubiquitin-signaling pathway, where it is assumed to have the same structure and function as wild-type ubiquitin (wt-Ub). However, the K0-Ub N-15 heteronuclear single quantum correlation NMR spectrum differs significantly from wt-Ub and the melting temperature is depressed by 19 degrees C, raising the question of the structural integrity and equivalence to wt-Ub. The three-dimensional structure of K0-Ub was determined by solution NMR, using chemical shift and residual dipolar coupling data. K0-Ub adopts the same backbone structure as wt-Ub, and all significant chemical shifts can be related to interactions impacted by the K to R mutations.
PDB Code(s):
C1 [Huang, Tao; Li, Jess; Byrd, R. Andrew] NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Byrd, RA (reprint author), NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM byrdra@mail.nih.gov
RI Byrd, R. Andrew/F-8042-2015
OI Byrd, R. Andrew/0000-0003-3625-4232
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health; Grant sponsor: National Cancer Institute; Grant sponsor: Center
for Cancer Research.
NR 33
TC 1
Z9 1
U1 2
U2 12
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 MAY
PY 2014
VL 23
IS 5
BP 662
EP 667
DI 10.1002/pro.2450
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AF3DU
UT WOS:000334592500015
PM 24591328
ER
PT J
AU Anjos, SM
Cohen, LG
Sterr, A
de Andrade, KNF
Conforto, AB
AF Anjos, Sarah M.
Cohen, Leonardo G.
Sterr, Annette
de Andrade, Karina N. F.
Conforto, Adriana B.
TI Translational Neurorehabilitation Research in the Third World What
Barriers to Trial Participation Can Teach Us
SO STROKE
LA English
DT Article
DE rehabilitation; stroke
ID INDUCED MOVEMENT THERAPY; UPPER EXTREMITY FUNCTION; STROKE INCIDENCE;
CASE-FATALITY; REHABILITATION; MANAGEMENT; MORTALITY; BRAZIL
AB Background and Purpose Most stroke rehabilitation studies have been performed in high-income countries. The aim of this study was to identify the main barriers for patient inclusion in a research protocol performed in Brazil.
MethodsWe evaluated reasons for exclusion of patients in a pilot, randomized, double-blinded clinical trial of stroke rehabilitation. Descriptive statistical analysis was performed.
ResultsOnly 5.6% of 571 screened patients were included. Recurrent stroke was responsible for exclusion of 45.4% of potentially eligible patients.
ConclusionsRecurrent stroke represented a big barrier to enroll patients in the protocol. External validity of rehabilitation trials will benefit from definition of study criteria according to regional characteristics of patients, including rates of recurrent stroke.
Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01333579.
C1 [Anjos, Sarah M.; de Andrade, Karina N. F.; Conforto, Adriana B.] Univ Sao Paulo, Hosp Clin, Neurol Clin Div, Dept Neurol, Sao Paulo, Brazil.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Rehabil Sect, NIH, Bethesda, MD 20892 USA.
[Sterr, Annette] Univ Surrey, Sch Psychol, Guildford GU2 5XH, Surrey, England.
[Conforto, Adriana B.] Hosp Israelita Albert Einstein, Sao Paulo, Brazil.
RP Anjos, SM (reprint author), Univ Sao Paulo, Hosp Clin, Neurol Clin Div, Av Dr Eneas C Aguiar,255-5084, Sao Paulo, Brazil.
EM sarah.m.anjos@gmail.com
RI DOS ANJOS, SARAH/G-9277-2015
OI DOS ANJOS, SARAH/0000-0002-7792-862X
FU Sao Paulo State's Foundation for Research Support (FAPESP)
[2006/55504-0]; National Council for Scientific and Technologic
Development (CNPq) [301883/2010-6]; FAPESP [2010/15660-8]; National
Institutes of Health [D71TW009132-01]
FX This study was funded by grant 2006/55504-0 from Sao Paulo State's
Foundation for Research Support (FAPESP). Dr Conforto received a
research scholarship from the National Council for Scientific and
Technologic Development (CNPq-2011-2013; 301883/2010-6). Training
scholarships were granted by FAPESP (2010-2012; 2010/15660-8) and by the
National Institutes of Health (2012-ongoing; grant D71TW009132-01) to
S.M. Anjos.
NR 15
TC 6
Z9 6
U1 0
U2 0
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 MAY
PY 2014
VL 45
IS 5
BP 1495
EP 1497
DI 10.1161/STROKEAHA.113.003572
PG 3
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA AG7DK
UT WOS:000335578100063
PM 24643406
ER
PT J
AU Doarn, CR
Pruitt, S
Jacobs, J
Harris, Y
Bott, DM
Riley, W
Lamer, C
Oliver, AL
AF Doarn, Charles R.
Pruitt, Sherilyn
Jacobs, Jessica
Harris, Yael
Bott, David M.
Riley, William
Lamer, Christopher
Oliver, Anthony L.
TI Original Research Federal Efforts to Define and Advance Telehealth-A
Work in Progress
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE telemedicine; telehealth; U; S; Government; healthcare reform
ID ARMY TELEMEDICINE; MOBILE HEALTH; TECHNOLOGY; FUTURE; CARE;
IMPLEMENTATION; PERSPECTIVES; MANAGEMENT; SUPPORT; HOME
AB Background:The integration of telecommunications and information systems in healthcare is not new or novel; indeed, it is the current practice of medicine and has been an integral part of medicine in remote locations for several decades. The U.S. Government has made a significant investment, measured in hundreds of millions of dollars, and therefore has a strong presence in the integration of telehealth/telemedicine in healthcare. However, the terminologies and definitions in the lexicon vary across agencies and departments of the U.S. Government. The objective of our survey was to identify and evaluate the definitions of telehealth/telemedicine across the U.S. Government to provide a better understanding of what each agency or department means when it uses these terms.Methodology:The U.S. Government, under the leadership of the Health Resources and Services Administration in the U.S. Department of Health and Human Services, established the Federal Telemedicine (FedTel) Working Group, through which all members responded to a survey on each agency or department's definition and use of terms associated with telehealth.Results and Conclusions:Twenty-six agencies represented by more than 100 individuals participating in the FedTel Working Group identified seven unique definitions of telehealth in current use across the U.S. Government. Although many definitions are similar, there are nuanced differences that reflect each organization's legislative intent and the population they serve. These definitions affect how telemedicine has been or is being applied across the healthcare landscape, reflecting the U.S. Government's widespread and influential role in healthcare access and service delivery. The evidence base suggests that a common nomenclature for defining telemedicine may benefit efforts to advance the use of this technology to address the changing nature of healthcare and new demands for services expected as a result of health reform.
C1 [Doarn, Charles R.] NASA Headquarters, Washington, DC USA.
[Doarn, Charles R.] Univ Cincinnati, Coll Med, Dept Family & Community Med, Cincinnati, OH 45267 USA.
[Pruitt, Sherilyn; Oliver, Anthony L.] US Dept HHS, Off Adv Telehlth, Rockville, MD USA.
[Jacobs, Jessica] Aetna, Washington, DC USA.
[Harris, Yael] US Dept HHS, Div Healthcare Qual, Off Dis Prevent & Hlth Promot, Rockville, MD USA.
[Bott, David M.] US Dept HHS, Ctr Medicare & Medicaid Serv, Baltimore, MD USA.
[Riley, William] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Lamer, Christopher] Indian Hlth Serv, Rockville, MD USA.
RP Doarn, CR (reprint author), Univ Cincinnati, Coll Med, Dept Family & Community Med, Cincinnati, OH 45267 USA.
EM charles.doarn@uc.edu
NR 36
TC 9
Z9 9
U1 0
U2 5
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 MAY 1
PY 2014
VL 20
IS 5
BP 409
EP 418
DI 10.1089/tmj.2013.0336
PG 10
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA AG4MG
UT WOS:000335393400004
PM 24502793
ER
PT J
AU Katritch, V
Fenalti, G
Abola, EE
Roth, BL
Cherezov, V
Stevens, RC
AF Katritch, Vsevolod
Fenalti, Gustavo
Abola, Enrique E.
Roth, Bryan L.
Cherezov, Vadim
Stevens, Raymond C.
TI Allosteric sodium in class A GPCR signaling
SO TRENDS IN BIOCHEMICAL SCIENCES
LA English
DT Review
DE GPCR activation; allosteric modulation; biased signaling; conserved
pocket; sodium ion; water binding
ID PROTEIN-COUPLED RECEPTORS; MU-OPIOID RECEPTOR; MUSCARINIC
ACETYLCHOLINE-RECEPTOR; RESOLUTION CRYSTAL-STRUCTURE; ALPHA-ADRENERGIC
RECEPTORS; SITE-DIRECTED MUTAGENESIS; A(2A) ADENOSINE RECEPTOR; 2ND
TRANSMEMBRANE DOMAIN; AMILORIDE ANALOGS; LIGAND-BINDING
AB Despite their functional and structural diversity, G protein-coupled receptors (GPCRs) share a common mechanism of signal transduction via conformational changes in the seven-transmembrane (7TM) helical domain. New major insights into this mechanism come from the recent crystallographic discoveries of a partially hydrated sodium ion that is specifically bound in the middle of the 7TM bundle of multiple class A GPCRs. This review discusses the remarkable structural conservation and distinct features of the Na+ pocket in this most populous GPCR class, as well as the conformational collapse of the pocket upon receptor activation. New insights help to explain allosteric effects of sodium on GPCR agonist binding and activation, and sodium's role as a potential co-factor in class A GPCR function.
C1 [Katritch, Vsevolod; Fenalti, Gustavo; Abola, Enrique E.; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Dept Pharmacol, NIMH,Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Chapel Hill Med Sch, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA.
RP Katritch, V (reprint author), Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM katritch@scripps.edu
RI Roth, Bryan/F-3928-2010; Cherezov, Vadim/L-9812-2013; Katritch,
Vsevolod/Q-8357-2016; Stevens, Raymond/K-7272-2015;
OI Cherezov, Vadim/0000-0002-5265-3914; Stevens,
Raymond/0000-0002-4522-8725; Katritch, Vsevolod/0000-0003-3883-4505
FU National Institute of General Medical Sciences (NIGMS) [U54 GM094618,
U19MH82441, R01DA017204]
FX This work was supported by the National Institute of General Medical
Sciences (NIGMS) PSI:Biology grants U54 GM094618 (V.K., V.C., and
R.C.S.), U19MH82441 (B.L.R.), and R01DA017204 (B.L.R.). We thank K.
Kadyshevskaya for assistance with figure preparation, A. Walker for
assistance with manuscript preparation, C. Tate, K. Jacobson, A.
IJzerman, and M. Audet for helpful discussions, and C. Tate for
providing unreleased coordinates of the 4BVN structure.
NR 106
TC 71
Z9 72
U1 4
U2 35
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0968-0004
J9 TRENDS BIOCHEM SCI
JI Trends Biochem.Sci.
PD MAY
PY 2014
VL 39
IS 5
BP 233
EP 244
DI 10.1016/j.tibs.2014.03.002
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH8BW
UT WOS:000336360100004
PM 24767681
ER
PT J
AU Viana, M
Mancy, R
Biek, R
Cleaveland, S
Cross, PC
Lloyd-Smith, JO
Haydon, DT
AF Viana, Mafalda
Mancy, Rebecca
Biek, Roman
Cleaveland, Sarah
Cross, Paul C.
Lloyd-Smith, James O.
Haydon, Daniel T.
TI Assembling evidence for identifying reservoirs of infection
SO TRENDS IN ECOLOGY & EVOLUTION
LA English
DT Review
ID CANINE-DISTEMPER VIRUS; APPROXIMATE BAYESIAN COMPUTATION; CRITICAL
COMMUNITY SIZE; METAPOPULATION DYNAMICS; DOMESTIC DOGS; VISCERAL
LEISHMANIASIS; TRANSMISSION RATES; RABIES ELIMINATION; POPULATION SIZES;
UNITED-STATES
AB Many pathogens persist in multihost systems, making the identification of infection reservoirs crucial for devising effective interventions. Here, we present a conceptual framework for classifying patterns of incidence and prevalence, and review recent scientific advances that allow us to study and manage reservoirs simultaneously. We argue that interventions can have a crucial role in enriching our mechanistic understanding of how reservoirs function and should be embedded as quasi-experimental studies in adaptive management frameworks. Single approaches to the study of reservoirs are unlikely to generate conclusive insights whereas the formal integration of data and methodologies, involving interventions, pathogen genetics, and contemporary surveillance techniques, promises to open up new opportunities to advance understanding of complex multihost systems.
C1 [Viana, Mafalda; Mancy, Rebecca; Biek, Roman; Cleaveland, Sarah; Haydon, Daniel T.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Biodivers Anim Hlth & Comparat Med, Boyd Orr Ctr Populat & Ecosyst Hlth, Glasgow G12 8QQ, Lanark, Scotland.
[Mancy, Rebecca] Univ Glasgow, Sch Comp Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Biek, Roman; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Cross, Paul C.] US Geol Survey, Northern Rocky Mt Sci Ctr, Bozeman, MT 59715 USA.
[Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
RP Viana, M (reprint author), Univ Glasgow, Coll Med Vet & Life Sci, Inst Biodivers Anim Hlth & Comparat Med, Boyd Orr Ctr Populat & Ecosyst Hlth, Glasgow G12 8QQ, Lanark, Scotland.
EM mafalda.viana@glasgow.ac.uk
RI Lloyd-Smith, James/K-4080-2012; Cross, Paul/K-6987-2012;
OI Lloyd-Smith, James/0000-0001-7941-502X; Cross, Paul/0000-0001-8045-5213;
Haydon, Daniel/0000-0002-1240-1886; Biek, Roman/0000-0003-3471-5357
FU RAPIDD programme of the Science and Technology Directorate of the US
Department of Homeland Security; National Institutes of Health Fogarty
International Center; Newton International Fellowship from The Royal
Society; EPSRC [EP/P505534/1]; NIH [RO1 AI047498]; National Science
Foundation [OCE-1335657]; De Logi Chair in Biological Sciences; UK
Medical Research Council [G0901135]; BBSRC [BB/H009302/1, BB/J010367/1]
FX This paper has roots in discussions at a 2010 workshop sponsored by the
RAPIDD programme of the Science and Technology Directorate of the US
Department of Homeland Security and National Institutes of Health
Fogarty International Center. We are grateful for comments contributed
by Seth Blumberg and Juliet Pulliam at that workshop. We also thank
Daniel Streicker and Andy Fenton for comments on this manuscript. M.V.
is funded by a Newton International Fellowship from The Royal Society,
R.M. is funded by EPSRC grant EP/P505534/1, R.B. is supported by NIH
grant RO1 AI047498, J.L-S. is funded by National Science Foundation
grant OCE-1335657 and the De Logi Chair in Biological Sciences, D.T.H.
is funded by the UK Medical Research Council (grant G0901135), and S.C.
is supported by the BBSRC (grant BB/H009302/1 and BB/J010367/1). Any
mention of trade, product, or firm names is for descriptive purposes
only and does not imply endorsement by the US Government.
NR 98
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Z9 43
U1 4
U2 54
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0169-5347
J9 TRENDS ECOL EVOL
JI Trends Ecol. Evol.
PD MAY
PY 2014
VL 29
IS 5
BP 270
EP 279
DI 10.1016/j.tree.2014.03.002
PG 10
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA AH4QR
UT WOS:000336113600006
PM 24726345
ER
PT J
AU Nussinov, R
Tsai, CJ
AF Nussinov, Ruth
Tsai, Chung-Jung
TI Unraveling structural mechanisms of allosteric drug action
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
DE allosteric drug discovery; protocol; agonist; antagonist; driver atom;
anchor atom; allostery
ID PROTEIN-KINASE PDK1; RECEPTOR ACTIVATION; 2-STATE MODEL; PATHWAYS;
SITES; COMMUNICATION; NETWORKS; DYNAMICS; MODULATION; INHIBITION
AB Orthosteric drugs block the active site to obstruct function; allosteric drugs modify the population of the active state, to modulate function. Available data lead us to propose that allosteric drugs can constitute anchors and drivers. The anchor docks into an allosteric pocket. The conformation with which it interacts is unchanged during the transition between the inactive and active states. The anchor provides the foundation that allows the driver to exert a 'pull' and/or 'push' action that shifts the receptor population from the inactive to the active state. The presence or absence of driver atom in an allosteric drug can exert opposite agonism. We map a strategy for driver identification and expect the allosteric trigger concept to transform agonist/antagonist drug discovery.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] Leidos Biomed Res Inc, NCI, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), Leidos Biomed Res Inc, NCI, Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM NussinoR@helix.nih.gov
FU National Cancer Institute, National Institutes of Health (NIH)
[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 (NIH) under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 64
TC 42
Z9 42
U1 8
U2 40
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD MAY
PY 2014
VL 35
IS 5
BP 256
EP 264
DI 10.1016/j.tips.2014.03.006
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AH5SB
UT WOS:000336190300006
PM 24742712
ER
PT J
AU Shin, EH
Caterson, EJ
Jackson, WM
Nesti, LJ
AF Shin, Emily H.
Caterson, Edward J.
Jackson, Wesley M.
Nesti, Leon J.
TI Quality of healing: Defining, quantifying, and enhancing skeletal muscle
healing
SO WOUND REPAIR AND REGENERATION
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; PROGENITOR CELLS; ENDOTHELIAL-CELLS; STRETCH
INJURY; MYOGENIC CELLS; SATELLITE CELL; STROMAL CELLS; DIFFERENTIATION;
TISSUE; REPAIR
AB Skeletal muscle injury is common in everyday physical activity and athletics, as well as in orthopedic trauma and disease. The overall functional disability resulting from muscle injury is directly related to the intrinsic healing properties of muscle and extrinsic treatment options designed to maximize repair and/or regeneration of muscle tissue all while minimizing pathologic healing pathways. It is important to understand the injury and repair pathways in order to improve the speed and quality of recovery. Recent military conflicts in Iraq and Afghanistan have highlighted the importance of successfully addressing muscular injury and showed the need for novel treatment options that will maximize functional regeneration of the damaged tissue. These severe, wartime injuries, when juxtaposed to peacetime, sports-related injuries, provide us with interesting case examples of the two extreme forms of muscular damage. Comparing and contrasting the differences in these healing pathways will likely provide helpful cues that will help physicians recapitulate the near complete repair and regeneration in less traumatic injuries in addition to more severe cases.
C1 [Shin, Emily H.; Nesti, Leon J.] NIAMSD, Dept Orthopaed Surg, Walter Reed Natl Mil Med Ctr, NIH, Bethesda, MD 20892 USA.
[Shin, Emily H.; Nesti, Leon J.] NIAMSD, Clin & Expt Orthopaed Grp, NIH, Bethesda, MD 20892 USA.
[Jackson, Wesley M.; Nesti, Leon J.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
[Caterson, Edward J.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
RP Nesti, LJ (reprint author), NIAMSD, NIH, Bldg 50,Room 1146,50 South Dr,MSC 8022, Bethesda, MD 20892 USA.
EM leonnesti@gmail.com
FU Department of Defense [DMRDP D10_1_AR_J5_920, USAMRAA W81XWH-09-2-0154]
FX We would like to thank the Department of Defense for their generous
support of this important work (DMRDP D10_1_AR_J5_920 and USAMRAA
W81XWH-09-2-0154).
NR 65
TC 4
Z9 4
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1067-1927
EI 1524-475X
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD MAY
PY 2014
VL 22
SU 1
SI SI
BP 18
EP 24
DI 10.1111/wrr.12163
PG 7
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA AG9SU
UT WOS:000335760800005
PM 24813360
ER
PT J
AU Gangjee, A
Pavana, RK
Ihnat, MA
Thorpe, JE
Disch, BC
Bastian, A
Bailey-Downs, LC
Hamel, E
Bai, R
AF Gangjee, Aleem
Pavana, Roheeth Kumar
Ihnat, Michael A.
Thorpe, Jessica E.
Disch, Bryan C.
Bastian, Anja
Bailey-Downs, Lora C.
Hamel, Ernest
Bai, Rouli
TI Discovery of Antitubulin Agents with Antiangiogenic Activity as Single
Entities with Multitarget Chemotherapy Potential
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Antitubulin; antimitotic; antiangiogenic; VEGFR2 inhibition; combination
chemotherapy
ID RECEPTOR TYROSINE KINASE; ANTI-ANGIOGENIC THERAPY; ANTITUMOR AGENTS;
INHIBITORS; RESISTANCE; DESIGN
AB Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI(50) values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.
C1 [Gangjee, Aleem; Pavana, Roheeth Kumar] Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA.
[Ihnat, Michael A.; Thorpe, Jessica E.; Bastian, Anja; Bailey-Downs, Lora C.] Univ Oklahoma, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73117 USA.
[Hamel, Ernest; Bai, Rouli] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
RP Gangjee, A (reprint author), Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA.
EM gangjee@duq.edu
RI Pavana, Roheeth/F-5839-2017
OI Pavana, Roheeth/0000-0001-6256-3683
FU NIH [CA136944, CA114021]; Duquesne University Adrian Van Kaam Chair in
Scholarly Excellence; NSF [CHE 0614785]
FX This work was supported, in part, by NIH Grants CA136944 (to A.G.),
CA114021 (to A.G.), the Duquesne University Adrian Van Kaam Chair in
Scholarly Excellence (to A.G.), and NSF equipment grant CHE 0614785 (for
the NMR).
NR 14
TC 7
Z9 7
U1 0
U2 10
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 MAY
PY 2014
VL 5
IS 5
BP 480
EP 484
DI 10.1021/ml4004793
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AH1KP
UT WOS:000335879300008
PM 24900865
ER
PT J
AU Liggins, C
Snyder, HM
Silverberg, N
Petanceska, S
Refolo, LM
Ryan, L
Carrillo, MC
AF Liggins, Charlene
Snyder, Heather M.
Silverberg, Nina
Petanceska, Suzana
Refolo, Lorenzo M.
Ryan, Laurie
Carrillo, Maria C.
TI International Alzheimer's Disease Research Portfolio (IADRP) aims to
capture global Alzheimer's disease research funding
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Alzheimer's disease; Research classification; Biomedical research;
Ontology
AB Alzheimer's disease (AD) is a recognized international public health crisis. There is an urgent need for public and private funding agencies around the world to coordinate funding strategies and leverage existing resources to enhance and expand support of AD research. To capture and compare their existing investments in AD research and research-related resources, major funding organizations are starting to utilize the Common Alzheimer's Disease Research Ontology (CADRO) to categorize their funding information. This information is captured in the International Alzheimer's Disease Research Portfolio (IADRP) for further analysis. As of January, 2014, over fifteen organizations from the US, Canada, Europe and Australia have contributed their information. The goal of the IADRP project is to enable funding organizations to assess the changing landscape of AD research and coordinate strategies, leverage resources, and avoid duplication of effort. (C) 2014 The Alzheimer's Association. All rights reserved.
C1 [Liggins, Charlene] NIA, Off Planning Anal & Evaluat, NIH, Bethesda, MD 20892 USA.
[Snyder, Heather M.; Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL 60631 USA.
[Silverberg, Nina; Petanceska, Suzana; Refolo, Lorenzo M.; Ryan, Laurie] NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA.
RP Snyder, HM (reprint author), Alzheimers Assoc, Chicago, IL 60631 USA.
EM heather.snyder@alz.org
NR 1
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD MAY
PY 2014
VL 10
IS 3
BP 405
EP 408
DI 10.1016/j.jalz.2013.12.013
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA AG7WG
UT WOS:000335628900016
PM 24780512
ER
PT J
AU Ablashi, D
Agut, H
Alvarez-Lafuente, R
Clark, DA
Dewhurst, S
DiLuca, D
Flamand, L
Frenkel, N
Gallo, R
Gompels, UA
Hollsberg, P
Jacobson, S
Luppi, M
Lusso, P
Malnati, M
Medveczky, P
Mori, Y
Pellett, PE
Pritchett, JC
Yamanishi, K
Yoshikawa, T
AF Ablashi, Dharam
Agut, Henri
Alvarez-Lafuente, Roberto
Clark, Duncan A.
Dewhurst, Stephen
DiLuca, Dario
Flamand, Louis
Frenkel, Niza
Gallo, Robert
Gompels, Ursula A.
Hollsberg, Per
Jacobson, Steven
Luppi, Mario
Lusso, Paolo
Malnati, Mauro
Medveczky, Peter
Mori, Yasuko
Pellett, Philip E.
Pritchett, Joshua C.
Yamanishi, Koichi
Yoshikawa, Tetsushi
TI Classification of HHV-6A and HHV-6B as distinct viruses
SO ARCHIVES OF VIROLOGY
LA English
DT Review
ID HUMAN-HERPESVIRUS 6; HUMAN-HERPESVIRUS-6 VARIANT-A; MULTIPLE-SCLEROSIS
PATIENTS; POLYMERASE-CHAIN-REACTION; STEM-CELL TRANSPLANTATION; HEALTHY
BLOOD-DONORS; MESSENGER-RNA LEVELS; REAL-TIME PCR; GLYCOPROTEIN-H;
FOLLOW-UP
AB Shortly after the discovery of human herpesvirus 6 (HHV-6), two distinct variants, HHV-6A and HHV-6B, were identified. In 2012, the International Committee on Taxonomy of Viruses (ICTV) classified HHV-6A and HHV-6B as separate viruses. This review outlines several of the documented epidemiological, biological, and immunological distinctions between HHV-6A and HHV-6B, which support the ICTV classification. The utilization of virus-specific clinical and laboratory assays for distinguishing HHV-6A and HHV-6B is now required for further classification. For clarity in biological and clinical distinctions between HHV-6A and HHV-6B, scientists and physicians are herein urged, where possible, to differentiate carefully between HHV-6A and HHV-6B in all future publications.
C1 [Ablashi, Dharam; Pritchett, Joshua C.] HHV 6 Fdn, Santa Barbara, CA USA.
[Agut, Henri] UPMC Paris 06, Grp Hosp Pitie Salpetriere, Paris, France.
[Alvarez-Lafuente, Roberto] Hosp Clin San Carlos, Madrid, Spain.
[Clark, Duncan A.] Barts Hlth NHS Trust, London, England.
[Dewhurst, Stephen] Univ Rochester, Med Ctr, Rochester, NY 14627 USA.
[DiLuca, Dario] Univ Ferrara, I-44100 Ferrara, Italy.
[Flamand, Louis] Univ Laval, Quebec City, PQ, Canada.
[Frenkel, Niza] Tel Aviv Univ, Inst Mol Virol, IL-69978 Tel Aviv, Israel.
[Gallo, Robert] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Gompels, Ursula A.] Univ London, London Sch Hyg & Trop Med, London, England.
[Hollsberg, Per] Aarhus Univ, Aarhus, Denmark.
[Jacobson, Steven] NINDS, NIH, Bethesda, MD 20892 USA.
[Luppi, Mario] Univ Modena & Reggio Emilia, Dept Med & Surg Sci, Modena, Italy.
[Lusso, Paolo] NIAID, NIH, Bethesda, MD 20892 USA.
[Malnati, Mauro] OSR Sci Inst, Milan, Italy.
[Medveczky, Peter] Univ S Florida, Tampa, FL USA.
[Mori, Yasuko] Kobe Univ, Grad Sch Med, Osaka, Japan.
[Pellett, Philip E.] Wayne State Univ, Sch Med, Detroit, MI USA.
[Yamanishi, Koichi] Osaka Univ, Res Fdn Microbial Dis, Osaka, Japan.
[Yoshikawa, Tetsushi] Fujita Hlth Univ, Sch Med, Toyoake, Aichi 47011, Japan.
RP Ablashi, D (reprint author), HHV 6 Fdn, Santa Barbara, CA USA.
EM Dharam_Ablashi@HHV-6Foundation.org
RI Di Luca, Dario/M-9781-2014; Luppi, Mario/J-3668-2016;
OI Di Luca, Dario/0000-0001-9643-9170; Luppi, Mario/0000-0002-0373-1154;
Medveczky, Peter/0000-0002-1798-2595; Dewhurst,
Stephen/0000-0001-7729-7920
FU Intramural NIH HHS [Z01 NS002817-18, Z01 NS002817-19, Z01 NS003040-01]
NR 134
TC 51
Z9 53
U1 0
U2 14
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD MAY
PY 2014
VL 159
IS 5
BP 863
EP 870
DI 10.1007/s00705-013-1902-5
PG 8
WC Virology
SC Virology
GA AG9ZB
UT WOS:000335777600003
PM 24193951
ER
PT J
AU Kuhn, JH
Bao, YM
Bavari, S
Becker, S
Bradfute, S
Brauburger, K
Brister, JR
Bukreyev, AA
Cai, YY
Chandran, K
Davey, RA
Dolnik, O
Dye, JM
Enterlein, S
Gonzalez, JP
Formenty, P
Freiberg, AN
Hensley, LE
Hoenen, T
Honko, AN
Ignatyev, GM
Jahrling, PB
Johnson, KM
Klenk, HD
Kobinger, G
Lackemeyer, MG
Leroy, EM
Lever, MS
Muhlberger, E
Netesov, SV
Olinger, GG
Palacios, G
Patterson, JL
Paweska, JT
Pitt, L
Radoshitzky, SR
Ryabchikova, EI
Saphire, EO
Shestopalov, AM
Smither, SJ
Sullivan, NJ
Swanepoel, R
Takada, A
Towner, JS
van der Groen, G
Volchkov, VE
Volchkova, VA
Wahl-Jensen, V
Warren, TK
Warfield, KL
Weidmann, M
Nichol, ST
AF Kuhn, Jens H.
Bao, Yiming
Bavari, Sina
Becker, Stephan
Bradfute, Steven
Brauburger, Kristina
Brister, J. Rodney
Bukreyev, Alexander A.
Cai, Yingyun
Chandran, Kartik
Davey, Robert A.
Dolnik, Olga
Dye, John M.
Enterlein, Sven
Gonzalez, Jean-Paul
Formenty, Pierre
Freiberg, Alexander N.
Hensley, Lisa E.
Hoenen, Thomas
Honko, Anna N.
Ignatyev, Georgy M.
Jahrling, Peter B.
Johnson, Karl M.
Klenk, Hans-Dieter
Kobinger, Gary
Lackemeyer, Matthew G.
Leroy, Eric M.
Lever, Mark S.
Muehlberger, Elke
Netesov, Sergey V.
Olinger, Gene G.
Palacios, Gustavo
Patterson, Jean L.
Paweska, Janusz T.
Pitt, Louise
Radoshitzky, Sheli R.
Ryabchikova, Elena I.
Saphire, Erica Ollmann
Shestopalov, Aleksandr M.
Smither, Sophie J.
Sullivan, Nancy J.
Swanepoel, Robert
Takada, Ayato
Towner, Jonathan S.
van der Groen, Guido
Volchkov, Viktor E.
Volchkova, Valentina A.
Wahl-Jensen, Victoria
Warren, Travis K.
Warfield, Kelly L.
Weidmann, Manfred
Nichol, Stuart T.
TI Virus nomenclature below the species level: a standardized nomenclature
for filovirus strains and variants rescued from cDNA
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID RECOMBINANT MARBURG VIRUS; EBOLA-VIRUS; FAMILY FILOVIRIDAE;
CELL-CULTURE; GUINEA-PIGS; IRF-3 ACTIVATION; IN-VITRO; REPLICATION;
TRANSCRIPTION; DOMAINS
AB Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, < virus name > (< strain >/)< isolation host-suffix >/< country of sampling >/< year of sampling >/< genetic variant designation >-< isolate designation >, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.
C1 [Kuhn, Jens H.; Cai, Yingyun; Hensley, Lisa E.; Jahrling, Peter B.; Lackemeyer, Matthew G.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD 21702 USA.
[Bao, Yiming; Brister, J. Rodney] NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Bavari, Sina; Dye, John M.; Honko, Anna N.; Olinger, Gene G.; Palacios, Gustavo; Pitt, Louise; Radoshitzky, Sheli R.; Warren, Travis K.] United States Army Med Res Inst Infect Dis, Frederick, MD USA.
[Becker, Stephan; Dolnik, Olga; Klenk, Hans-Dieter] Univ Marburg, Inst Virol, D-35032 Marburg, Germany.
[Bradfute, Steven] Univ New Mexico, Albuquerque, NM 87131 USA.
[Brauburger, Kristina; Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Brauburger, Kristina; Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Lab, Boston, MA 02118 USA.
[Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA.
[Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA.
[Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Davey, Robert A.; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA.
[Enterlein, Sven; Warfield, Kelly L.] Integrated BioTherapeut Inc, Gaithersburg, MD USA.
[Gonzalez, Jean-Paul] Inst Rech Dev, Dept Hlth, Marseille, France.
[Gonzalez, Jean-Paul] Metabiota Inc, San Francisco, CA USA.
[Formenty, Pierre] World Hlth Org, Geneva, Switzerland.
[Hoenen, Thomas] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Ignatyev, Georgy M.] Minist Hlth Russian Federat, Fed State Unitary Co Microgen Sci Ind Co Immunobi, Moscow, Russia.
[Kobinger, Gary] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada.
[Leroy, Eric M.] Ctr Int Rech Med Franceville, Franceville, Gabon.
[Lever, Mark S.; Smither, Sophie J.] Dstl, Dept Biomed Sci, Salisbury, Wilts, England.
[Netesov, Sergey V.; Shestopalov, Aleksandr M.] Novosibirsk State Univ, Novosibirsk 630090, Novosibirsk Reg, Russia.
[Paweska, Janusz T.] Natl Inst Communicable Dis, Ctr Emerging & Zoonot Dis, Natl Hlth Lab Serv, Sandringham Johannesburg, Gauteng, South Africa.
[Ryabchikova, Elena I.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Novosibirsk Reg, Russia.
[Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.
[Shestopalov, Aleksandr M.] State Res Ctr Virol & Biotechnol Vector, Koltsov, Novosibirsk Reg, Russia.
[Sullivan, Nancy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Swanepoel, Robert] Univ Pretoria, Zoonoses Res Unit, ZA-0002 Pretoria, South Africa.
[Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan.
[Towner, Jonathan S.; Nichol, Stuart T.] Ctr Dis Control & Prevent CDC, Natl Ctr Emerging & Zoonot Infect Dis NCEZID, Div High Consequence Pathogens Pathol DHCPP, Viral Special Pathogens Branch VSPB, Atlanta, GA 30333 USA.
[van der Groen, Guido] Prins Leopold Inst Trop Geneeskunde, Antwerp, Belgium.
[Volchkov, Viktor E.; Volchkova, Valentina A.] Univ Lyon, Lab Filovirus, INSERM, U758,UCB Lyon 1,Ecole Normale Super Lyon, Lyon, France.
[Weidmann, Manfred] Univ Med Gottingen, Abt Virol, Gottingen, Germany.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA.
EM kuhnjens@mail.nih.gov; stn1@cdc.gov
RI LEROY, Eric/I-4347-2016; Volchkov, Viktor/M-7846-2014; Kuhn, Jens
H./B-7615-2011; Ryabchikova, Elena /G-3089-2013; Netesov,
Sergey/A-3751-2013; Becker, Stephan/A-1065-2010; Palacios,
Gustavo/I-7773-2015; Weidmann, Manfred/G-1817-2015;
OI LEROY, Eric/0000-0003-0022-0890; Hoenen, Thomas/0000-0002-5829-6305;
Volchkov, Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045;
Ryabchikova, Elena /0000-0003-4714-1524; Netesov,
Sergey/0000-0002-7786-2464; Becker, Stephan/0000-0002-2794-5659;
Palacios, Gustavo/0000-0001-5062-1938; Weidmann,
Manfred/0000-0002-7063-7491; Shestopalov, Alexander/0000-0002-9734-0620;
Honko, Anna/0000-0001-9165-148X
FU Joint Science and Technology Office for Chem Bio Defense
[TMTI0048_09_RD_T]; NIAID [HHSN272200700016I]; Intramural Research
Program of the NIH, National Library of Medicine; Intramural Research
Program of the NIH, NIAID
FX The content of this publication does not necessarily reflect the views
or policies of the US Department of the Army, the US Department of
Defense or the US Department of Health and Human Services or of the
institutions and companies affiliated with the authors. This work was
funded in part by the Joint Science and Technology Office for Chem Bio
Defense (proposal #TMTI0048_09_RD_T to SB). YC, JHK, and VWJ performed
this work as employees of Tunnell Consulting, Inc., and MGL as an
employee of Lovelace Respiratory Research Institute, both subcontractors
to Battelle Memorial Institute under its prime contract with NIAID,
under Contract No. HHSN272200700016I. This research was also supported
in part by the Intramural Research Program of the NIH, National Library
of Medicine (YB and JRB), and the Intramural Research Program of the
NIH, NIAID (TH).
NR 35
TC 26
Z9 28
U1 0
U2 21
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD MAY
PY 2014
VL 159
IS 5
BP 1229
EP 1237
DI 10.1007/s00705-013-1877-2
PG 9
WC Virology
SC Virology
GA AG9ZB
UT WOS:000335777600048
PM 24190508
ER
PT J
AU Cotmore, SF
Agbandje-McKenna, M
Chiorini, JA
Mukha, DV
Pintel, DJ
Qiu, JM
Soderlund-Venermo, M
Tattersall, P
Tijssen, P
Gatherer, D
Davison, AJ
AF Cotmore, Susan F.
Agbandje-McKenna, Mavis
Chiorini, John A.
Mukha, Dmitry V.
Pintel, David J.
Qiu, Jianming
Soderlund-Venermo, Maria
Tattersall, Peter
Tijssen, Peter
Gatherer, Derek
Davison, Andrew J.
TI The family Parvoviridae
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID VIRUSES
AB A set of proposals to rationalize and extend the taxonomy of the family Parvoviridae is currently under review by the International Committee on Taxonomy of Viruses (ICTV). Viruses in this family infect a wide range of hosts, as reflected by the longstanding division into two subfamilies: the Parvovirinae, which contains viruses that infect vertebrate hosts, and the Densovirinae, encompassing viruses that infect arthropod hosts. Using a modified definition for classification into the family that no longer demands isolation as long as the biological context is strong, but does require a near-complete DNA sequence, 134 new viruses and virus variants were identified. The proposals introduce new species and genera into both subfamilies, resolve one misclassified species, and improve taxonomic clarity by employing a series of systematic changes. These include identifying a precise level of sequence similarity required for viruses to belong to the same genus and decreasing the level of sequence similarity required for viruses to belong to the same species. These steps will facilitate recognition of the major phylogenetic branches within genera and eliminate the confusion caused by the near-identity of species and viruses. Changes to taxon nomenclature will establish numbered, non-Latinized binomial names for species, indicating genus affiliation and host range rather than recapitulating virus names. Also, affixes will be included in the names of genera to clarify subfamily affiliation and reduce the ambiguity that results from the vernacular use of "parvovirus" and "densovirus" to denote multiple taxon levels.
C1 [Cotmore, Susan F.; Tattersall, Peter] Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
[Agbandje-McKenna, Mavis] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Ctr Struct Biol,McKnight Brain Inst, Gainesville, FL 32610 USA.
[Chiorini, John A.] NIH, Mol Physiol & Therapeut Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA.
[Mukha, Dmitry V.] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia.
[Pintel, David J.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Life Sci Ctr, Columbia, MO 65212 USA.
[Qiu, Jianming] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66103 USA.
[Soderlund-Venermo, Maria] Univ Helsinki, Dept Virol, Haartman Inst, Helsinki, Finland.
[Tattersall, Peter] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Tijssen, Peter] INRS Inst Armand Frappier, Laval, PQ, Canada.
[Gatherer, Derek; Davison, Andrew J.] Univ Glasgow, Ctr Virus Res, MRC, Glasgow, Lanark, Scotland.
RP Cotmore, SF (reprint author), Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA.
EM susan.cotmore@yale.edu
OI Gatherer, Derek/0000-0002-7385-5734
FU Public Health Service grants from the National Institutes of Health
[CA029303, AI026109, AI046458, AI091588, AI070723, GM082946]; National
Science Foundation [MCB 0718948]; UK Medical Research Council; Helsinki
University Research Funds; Natural Sciences and Engineering Research
Council of Canada; Juselius Foundation, Finland
FX This work was supported in part by Public Health Service grants from the
National Institutes of Health (CA029303 and AI026109), SFC and PTa;
(AI046458 and AI091588), DJP; (AI070723), JQ; (GM082946), MAM; the
National Science Foundation (MCB 0718948), MAM; the UK Medical Research
Council, AD and DG; the Helsinki University Research Funds and Juselius
Foundation, Finland, MSV; and the Natural Sciences and Engineering
Research Council of Canada, PTi.
NR 16
TC 112
Z9 119
U1 7
U2 28
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
EI 1432-8798
J9 ARCH VIROL
JI Arch. Virol.
PD MAY
PY 2014
VL 159
IS 5
BP 1239
EP 1247
DI 10.1007/s00705-013-1914-1
PG 9
WC Virology
SC Virology
GA AG9ZB
UT WOS:000335777600049
PM 24212889
ER
PT J
AU Huber, AM
Mamyrova, G
Lachenbruch, PA
Lee, JA
Katz, JD
Targoff, IN
Miller, FW
Rider, LG
AF Huber, Adam M.
Mamyrova, Gulnara
Lachenbruch, Peter A.
Lee, Julia A.
Katz, James D.
Targoff, Ira N.
Miller, Frederick W.
Rider, Lisa G.
CA Childhood Myositis Heterogeneity
TI Early Illness Features Associated With Mortality in the Juvenile
Idiopathic Inflammatory Myopathies
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID LONG-TERM SURVIVAL; CLINICAL CHARACTERISTICS; DERMATOMYOSITIS;
POLYMYOSITIS; MYOSITIS; OUTCOMES; CLASSIFICATION; AUTOANTIBODY;
PHENOTYPES; CHILDHOOD
AB Objective
Because juvenile idiopathic inflammatory myopathies (IIMs) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for juvenile IIM mortality.
Methods
Mortality status was available for 405 patients (329 with juvenile dermatomyositis [DM], 30 with juvenile polymyositis [PM], and 46 with juvenile connective tissue disease-associated myositis [CTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMRs) were calculated using US population statistics. Cox regression analysis was used to assess univariable associations with mortality, and random survival forest (RSF) classification and Cox regression analysis were used for multivariable associations.
Results
Of 17 deaths (4.2% overall mortality), 8 (2.4%) were in juvenile DM patients. Death was related to the pulmonary system (primarily interstitial lung disease [ILD]) in 7 patients, gastrointestinal system in 3, and multisystem in 3, and of unknown etiology in 4 patients. The SMR for juvenile IIMs overall was 14.4 (95% confidence interval [95% CI] 12.2-16.5) and was 8.3 (95% CI 6.4-10.3) for juvenile DM. The top mortality risk factors in the univariable analysis included clinical subgroup (juvenile CTM, juvenile PM), antisynthetase autoantibodies, older age at diagnosis, ILD, and Raynaud's phenomenon at diagnosis. In multivariable analyses, clinical subgroup, illness severity at onset, age at diagnosis, weight loss, and delay to diagnosis were the most important predictors from RSF; clinical subgroup and illness severity at onset were confirmed by multivariable Cox regression analysis.
Conclusion
Overall mortality was higher in juvenile IIM patients, and several early illness features were identified as risk factors. Clinical subgroup, antisynthetase autoantibodies, older age at diagnosis, and ILD are also recognized as mortality risk factors in adult myositis.
C1 [Huber, Adam M.] IWK Hlth Ctr, Halifax, NS, Canada.
[Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada.
[Mamyrova, Gulnara; Katz, James D.] George Washington Univ, Sch Med, Washington, DC USA.
[Lachenbruch, Peter A.; Lee, Julia A.; Miller, Frederick W.; Rider, Lisa G.] NIEHS, NIH, Bethesda, MD USA.
[Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, VAMC, Oklahoma City, OK USA.
[Targoff, Ira N.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
RP Rider, LG (reprint author), Natl Inst Environm Sci, Environm Autoimmun Grp, NIH, Clin Res Ctr, Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
FU NIH, National Institute of Environmental Health Sciences; National
Institute of Arthritis and Musculoskeletal and Skin Diseases; Center for
Biologics Evaluation and Research, FDA; Cure JM Foundation; Amgen;
Pfizer
FX Supported in part by the Intramural Research Programs of the NIH,
National Institute of Environmental Health Sciences, and National
Institute of Arthritis and Musculoskeletal and Skin Diseases, and by the
Center for Biologics Evaluation and Research, FDA. Dr. Mamyrova's work
was supported by the Cure JM Foundation.; Dr. Lachenbruch has received
consulting fees, speaking fees, and/or honoraria (less than $10,000
each) from Amgen and Pfizer.
NR 31
TC 9
Z9 9
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 MAY
PY 2014
VL 66
IS 5
BP 732
EP 740
DI 10.1002/acr.22212
PG 9
WC Rheumatology
SC Rheumatology
GA AF4CI
UT WOS:000334658600012
PM 24151254
ER
PT J
AU Kraft, LJ
Nguyen, TA
Vogel, SS
Kenworthy, AK
AF Kraft, Lewis J.
Nguyen, Tuan A.
Vogel, Steven S.
Kenworthy, Anne K.
TI Size, stoichiometry, and organization of soluble LC3-associated
complexes
SO AUTOPHAGY
LA English
DT Article
DE MAP1LC3B; FRAP; FPFA; fluorescence; FRET; diffusion; autophagy; FCS;
hydrodynamic radius; ATG8
ID FLUORESCENCE CORRELATION SPECTROSCOPY; LASER-SCANNING MICROSCOPES;
SELECTIVE AUTOPHAGY; FLUCTUATION SPECTROSCOPY; PROTEIN LIPIDATION;
STRUCTURAL BASIS; CONFOCAL FRAP; CELL-DEATH; LC3; ATG8
AB MAP1LC3B, an ortholog of yeast Atg8 and a member of the family of proteins formerly also known as ATG8 in mammals (LC3B henceforth in the text), functions in autophagosome formation and autophagy substrate recruitment. LC3 exists in both a soluble (autophagosome-independent) form as well as a lipid modified form that becomes tightly incorporated into autophagosomal membranes. Although LC3 is known to associate with tens of proteins, relatively little is known about soluble LC3 aside from its interactions with the LC3 lipid conjugation machinery. In previous studies we found autophagosome-independent GFP-LC3B diffuses unusually slowly for a protein of its size, suggesting it may constitutively associate with a high molecular weight complex, form homo-oligomers or aggregates, or reversibly bind microtubules or membranes. To distinguish between these possibilities, we characterized the size, stoichiometry, and organization of autophagosome-independent LC3B in living cells and in cytoplasmic extracts using fluorescence recovery after photobleaching (FRAP) and fluorescence polarization fluctuation analysis (FPFA). We found that the diffusion of LC3B was unaffected by either mutational disruption of its lipid modification or microtubule depolymerization. Brightness and homo-FRET analysis indicate LC3B does not homo-oligomerize. However, mutation of specific residues on LC3B required for binding other proteins and mRNA altered the effective hydrodynamic radius of the protein as well as its stoichiometry. We conclude that when not bound to autophagosomes, LC3B associates with a multicomponent complex with an effective size of similar to 500 kDa in the cytoplasm. These findings provide new insights into the nature of soluble LC3B and illustrate the power of FRAP and FPFA to investigate the emergent properties of protein complexes in the autophagy pathway.
C1 [Kraft, Lewis J.; Kenworthy, Anne K.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Dept Cell & Dev Biol, Chem & Phys Biol Program,Med Ctr, Nashville, TN 37232 USA.
[Nguyen, Tuan A.; Vogel, Steven S.] NIAAA, Sect Cellular Biophoton, Lab Mol Physiol, NIH, Rockville, MD 20852 USA.
RP Kenworthy, AK (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, Dept Cell & Dev Biol, Chem & Phys Biol Program,Med Ctr, Nashville, TN 37232 USA.
EM Anne.kenworthy@vanderbilt.edu
OI Kraft, Lewis/0000-0001-8663-0596; Vogel, Steven/0000-0002-3005-2667
FU National Science Foundation [NSF/DMS 0970008]; National Institutes of
Health, National Institute on Alcohol Abuse and Alcoholism, Bethesda,
MD; National Institute of Diabetes and Digestive and Kidney Disease
[DK020593]
FX We are grateful for the constructive criticism and advice from the other
members of the Kenworthy laboratory and to Dr Christian Behrends for
helpful discussions. This work was funded by grant NSF/DMS 0970008 from
the National Science Foundation, by the intramural program of the
National Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism, Bethesda, MD, and utilized the core(s) of the Vanderbilt
Diabetes Research and Training Center funded by grant DK020593 from the
National Institute of Diabetes and Digestive and Kidney Disease. The
funding sources had no role in the study design, collection, analysis or
interpretation of data, writing the report, or the decision to submit
the paper for publication.
NR 60
TC 5
Z9 5
U1 1
U2 14
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD MAY 1
PY 2014
VL 10
IS 5
BP 861
EP 877
DI 10.4161/auto.28175
PG 17
WC Cell Biology
SC Cell Biology
GA AG5BI
UT WOS:000335433700011
PM 24646892
ER
PT J
AU Jun, HS
Weinstein, DA
Lee, YM
Mansfield, BC
Chou, JY
AF Jun, Hyun Sik
Weinstein, David A.
Lee, Young Mok
Mansfield, Brian C.
Chou, Janice Y.
TI Molecular mechanisms of neutrophil dysfunction in glycogen storage
disease type Ib
SO BLOOD
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; COLONY-STIMULATING FACTOR; ACTIVATED
RECEPTOR-GAMMA; CONGENITAL NEUTROPENIA; NADPH OXIDASE; RESPIRATORY
BURST; GLUCOSE-TRANSPORT; MUTATIONS; CELLS; 1B
AB Glycogen storage disease type Ib (GSD-Ib) is an autosomal-recessive syndrome characterized by neutropenia and impaired glucose homeostasis resulting from a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT). The underlying cause of GSD-Ib neutropenia is an enhanced neutrophil apoptosis, but patients also manifest neutrophil dysfunction of unknown etiology. Previously, we showed G6PT interacts with the enzyme glucose-6-phosphatase-beta (G6Pase-beta) to regulate the availability of G6P/glucose in neutrophils. Adeficiency in G6Pase-beta activity in neutrophils impairs both their energy homeostasis and function. We now show that G6PT-deficient neutrophils from GSD-Ib patients are similarly impaired. Their energy impairment is characterized by decreased glucose uptake and reduced levels of intracellular G6P, lactate, adenosine triphosphate, and reduced NAD phosphate, whereas functional impairment is reflected in reduced neutrophil respiratory burst, chemotaxis, and calcium mobilization. We further show that the mechanism of neutrophil dysfunction in GSD-Ib arises from activation of the hypoxia-inducible factor-1 alpha/peroxisome-proliferators-activated receptor-gamma pathway.
C1 [Jun, Hyun Sik; Lee, Young Mok; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Weinstein, David A.] Univ Florida, Dept Pediat, Div Pediat Endocrinol, Glycogen Storage Dis Program, Gainesville, FL USA.
[Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD USA.
RP Chou, JY (reprint author), NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
OI Mansfield, Brian/0000-0002-8533-2789
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH; University of Florida Foundation; Rural Development
Administration, Republic of Korea [PJ008196/PJ008127]
FX This research was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH. Additional support was provided by the following
philanthropic funds managed through the University of Florida
Foundation: Jonah Pournazarian Type Ib GSD Research Fund, the Efforts
for Ellie Fund, Jamie Konieczka Type Ib GSD Research Fund, Jerry
Kaczur's Fund, and the Type Ib Glycogen Storage Disease Research Fund.
Additional support was also provided by the next generation of
BioGreen21 project (PJ008196/PJ008127) from the Rural Development
Administration, Republic of Korea.
NR 49
TC 9
Z9 9
U1 2
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 1
PY 2014
VL 123
IS 18
BP 2843
EP 2853
DI 10.1182/blood-2013-05-502435
PG 11
WC Hematology
SC Hematology
GA AH1QP
UT WOS:000335896300019
PM 24565827
ER
PT J
AU Purdue, MP
Hofmann, JN
Kemp, TJ
Chaturvedi, AK
Lan, Q
Park, JH
Pfeiffer, RM
Hildesheim, A
Pinto, LA
Rothman, N
AF Purdue, Mark P.
Hofmann, Jonathan N.
Kemp, Troy J.
Chaturvedi, Anil K.
Lan, Qing
Park, Ju-Hyun
Pfeiffer, Ruth M.
Hildesheim, Allan
Pinto, Ligia A.
Rothman, Nathaniel
TI A prospective study of 67 serum immune and inflammation markers and risk
of non-Hodgkin lymphoma (vol 122, pg 951, 2013)
SO BLOOD
LA English
DT Correction
C1 [Purdue, Mark P.; Hofmann, Jonathan N.; Chaturvedi, Anil K.; Lan, Qing; Pfeiffer, Ruth M.; Hildesheim, Allan; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Kemp, Troy J.; Pinto, Ligia A.] SAIC Frederick Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Park, Ju-Hyun] Dongguk Univ Seoul, Seoul, South Korea.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RI Hildesheim, Allan/B-9760-2015; Purdue, Mark/C-9228-2016
OI Hildesheim, Allan/0000-0003-0257-2363; Purdue, Mark/0000-0003-1177-3108
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 1
PY 2014
VL 123
IS 18
BP 2901
EP 2901
DI 10.1182/blood-2014-03-563767
PG 1
WC Hematology
SC Hematology
GA AH1QP
UT WOS:000335896300029
ER
PT J
AU Schloesser, RJ
Jimenez, DV
Hardy, NF
Paredes, D
Catlow, BJ
Manji, HK
McKay, RD
Martinowich, K
AF Schloesser, Robert J.
Jimenez, Dennisse V.
Hardy, Nicholas F.
Paredes, Daniel
Catlow, Briony J.
Manji, Husseini K.
McKay, Ronald D.
Martinowich, Keri
TI Atrophy of pyramidal neurons and increased stress-induced glutamate
levels in CA3 following chronic suppression of adult neurogenesis
SO BRAIN STRUCTURE & FUNCTION
LA English
DT Article
DE Neurogenesis; Dentate gyrus; Excitotoxicity; Atrophy; Dendrite; CA3
ID ENHANCED SYNAPTIC PLASTICITY; HIPPOCAMPAL-FORMATION VOLUME; NEWLY
GENERATED NEURONS; DENTATE GYRUS; CAPILLARY ELECTROPHORESIS;
CHRONIC-SCHIZOPHRENIA; PSYCHOSOCIAL STRESS; ANXIETY DISORDERS; SELECTIVE
LOSS; GRANULE CELLS
AB Following their birth in the adult hippocampal dentate gyrus, newborn progenitor cells migrate into the granule cell layer where they differentiate, mature, and functionally integrate into existing circuitry. The hypothesis that adult hippocampal neurogenesis is physiologically important has gained traction, but the precise role of newborn neurons in hippocampal function remains unclear. We investigated whether loss of new neurons impacts dendrite morphology and glutamate levels in area CA3 of the hippocampus by utilizing a human GFAP promoter-driven thymidine kinase genetic mouse model to conditionally suppress adult neurogenesis. We found that chronic ablation of new neurons induces remodeling in CA3 pyramidal cells and increases stress-induced release of the neurotransmitter glutamate. The ability of persistent impairment of adult neurogenesis to influence hippocampal dendrite morphology and excitatory amino acid neurotransmission has important implications for elucidating newborn neuron function, and in particular, understanding the role of these cells in stress-related excitoxicity.
C1 [Schloesser, Robert J.; Jimenez, Dennisse V.; Manji, Husseini K.; Martinowich, Keri] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Schloesser, Robert J.; Jimenez, Dennisse V.; Hardy, Nicholas F.; Paredes, Daniel; Catlow, Briony J.; McKay, Ronald D.; Martinowich, Keri] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Schloesser, Robert J.] Univ Maryland, Dept Psychiat, Sch Med, Baltimore, MD 21201 USA.
[Hardy, Nicholas F.; Martinowich, Keri] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Paredes, Daniel; Catlow, Briony J.; McKay, Ronald D.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Janssen Res & Dev, Titusville, NJ USA.
RP Martinowich, K (reprint author), Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 N Wolfe St,347B, Baltimore, MD 21205 USA.
EM keri.martinowich@libd.org
RI Martinowich, Keri/F-9841-2012;
OI Martinowich, Keri/0000-0002-5237-0789
FU National Institute of Mental Health Intramural Research Program; Lieber
Institute for Brain Development; NARSAD Young Investigator Awards
FX This work was funded by the National Institute of Mental Health
Intramural Research Program and the Lieber Institute for Brain
Development. RJS and KM were supported in part by NARSAD Young
Investigator Awards.
NR 62
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Z9 8
U1 2
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2653
EI 1863-2661
J9 BRAIN STRUCT FUNCT
JI Brain Struct. Funct.
PD MAY
PY 2014
VL 219
IS 3
BP 1139
EP 1148
DI 10.1007/s00429-013-0532-8
PG 10
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA AG9KK
UT WOS:000335737900025
PM 23483239
ER
PT J
AU Gough, SM
Lee, F
Yang, F
Walker, RL
Zhu, YLJ
Pineda, M
Onozawa, M
Chung, YJ
Bilke, S
Wagner, EK
Denu, JM
Ning, Y
Xu, BW
Wang, GG
Meltzer, PS
Aplan, PD
AF Gough, Sheryl M.
Lee, Fan
Yang, Fan
Walker, Robert L.
Zhu, Yeulin J.
Pineda, Marbin
Onozawa, Masahiro
Chung, Yang Jo
Bilke, Sven
Wagner, Elise K.
Denu, John M.
Ning, Yi
Xu, Bowen
Wang, Gang Greg
Meltzer, Paul S.
Aplan, Peter D.
TI NUP98-PHF23 Is a Chromatin-Modifying Oncoprotein That Causes a Wide
Array of Leukemias Sensitive to Inhibition of PHD Histone Reader
Function
SO CANCER DISCOVERY
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION
PROFILES; DOUBLE-TRANSGENIC MICE; EMBRYONIC STEM-CELLS; MLL
TRANSLOCATIONS; HOMEOBOX GENES; MALIGNANCIES; ACTIVATION; TRANSCRIPTION
AB In this report, we show that expression of a NUP98-PHF23 (NP23) fusion, associated with acute myeloid leukemia (AML) in humans, leads to myeloid, erythroid, T-cell, and B-cell leukemia in mice. The leukemic and preleukemic tissues display a stem cell-like expression signature, including Hoxa, Hoxb, and Meis1 genes. The PHF23 plant homeodomain (PHD) motif is known to bind to H3K4me3 residues, and chromatin immunoprecipitation experiments demonstrated that the NP23 protein binds to chromatin at a specific subset of H3K4me3 sites, including at Hoxa, Hoxb, and Meis1. Treatment of NP23 cells with disulfiram, which inhibits the binding of PHD motifs to H3K4me3, rapidly and selectively killed NP23-expressing myeloblasts; cell death was preceded by decreased expression of Hoxa, Hoxb, and Meis1. Furthermore, AML driven by a related fusion gene, NUP98-JARID1A (NJL), was also sensitive to disulfiram. Thus, the NP23 mouse provides a platform to evaluate compounds that disrupt binding of oncogenic PHD proteins to H3K4me3.
SIGNIFICANCE: NP23 and NJL belong to a subset of chromatin-modifying fusion oncoproteins that cause leukemia characterized by overexpression of Hoxa and Meis1 genes. Inhibition of NP23 binding to H3K4me3 at Hoxa and Meis1 loci by disulfiram, a U.S. Food and Drug Administration-approved drug, leads to leukemic cell death, demonstrating the feasibility of targeting this subset of oncoproteins. (C) 2014 AACR.
C1 [Gough, Sheryl M.; Lee, Fan; Yang, Fan; Walker, Robert L.; Zhu, Yeulin J.; Pineda, Marbin; Onozawa, Masahiro; Chung, Yang Jo; Bilke, Sven; Meltzer, Paul S.; Aplan, Peter D.] NCI, Genet Branch Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ning, Yi] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Wagner, Elise K.; Denu, John M.] Univ Wisconsin, Dept Biomol Chem, Madison, WI USA.
[Xu, Bowen; Wang, Gang Greg] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.
RP Aplan, PD (reprint author), NCI, Genet Branch Ctr Canc Res, NIH, Bldg 37,Room 6002,37 Convent Dr, Bethesda, MD 20892 USA.
EM aplanp@mail.nih.gov
RI Wang, G Greg/L-6666-2014; Aplan, Peter/K-9064-2016
OI Wang, G Greg/0000-0002-7210-9940;
FU National Cancer Institute, National Institutes of Health [ZIA SC 010378,
BC 010983]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (grant numbers
ZIA SC 010378 and BC 010983).
NR 50
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U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD MAY
PY 2014
VL 4
IS 5
BP 564
EP 577
DI 10.1158/2159-8290.CD-13-0419
PG 14
WC Oncology
SC Oncology
GA AH1ZA
UT WOS:000335919200027
PM 24535671
ER
PT J
AU de Bruin, EC
Cowell, C
Warne, PH
Jiang, M
Saunders, RE
Melnick, MA
Gettinger, S
Walther, Z
Wurtz, A
Heynen, GJ
Heideman, DAM
Gomez-Roman, J
Garcia-Castano, A
Gong, YX
Ladanyi, M
Varmus, H
Bernards, R
Smit, EF
Politi, K
Downward, J
AF de Bruin, Elza C.
Cowell, Catherine
Warne, Patricia H.
Jiang, Ming
Saunders, Rebecca E.
Melnick, Mary Ann
Gettinger, Scott
Walther, Zenta
Wurtz, Anna
Heynen, Guus J.
Heideman, Danielle A. M.
Gomez-Roman, Javier
Garcia-Castano, Almudena
Gong, Yixuan
Ladanyi, Marc
Varmus, Harold
Bernards, Rene
Smit, Egbert F.
Politi, Katerina
Downward, Julian
TI Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung
Cancer
SO CANCER DISCOVERY
LA English
DT Article
ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; ERLOTINIB RESISTANCE;
TUMOR-SUPPRESSOR; RAF INHIBITION; RECEPTOR; MUTATIONS; GEFITINIB;
AMPLIFICATION; ADENOCARCINOMA
AB Activating mutations in the EGF receptor (EGFR) are associated with clinical responsiveness to EGFR tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib. However, resistance eventually arises, often due to a second EGFR mutation, most commonly T790M. Through a genome-wide siRNA screen in a human lung cancer cell line and analyses of murine mutant EGFR-driven lung adenocarcinomas, we found that erlotinib resistance was associated with reduced expression of neurofibromin, the RAS GTPase-activating protein encoded by the NF1 gene. Erlotinib failed to fully inhibit RAS-ERK signaling when neurofibromin levels were reduced. Treatment of neurofibromin-deficient lung cancers with a MAP-ERK kinase (MEK) inhibitor restored sensitivity to erlotinib. Low levels of NF1 expression were associated with primary and acquired resistance of lung adenocarcinomas to EGFR TKIs in patients. These findings identify a subgroup of patients with EGFR-mutant lung adenocarcinoma who might benefit from combination therapy with EGFR and MEK inhibitors.
SIGNIFICANCE: The emergence of resistance to EGFR TKIs is a major clinical challenge in the treatment of lung adenocarcinomas driven by mutations in EGFR. This study suggests that, in a subset of patients, resistance is caused by reduced neurofibromin expression, and that in these cases there may be clinical benefit to combining EGFR TKIs with MEK inhibitors. (C) 2014 AACR.
C1 [de Bruin, Elza C.; Cowell, Catherine; Warne, Patricia H.; Downward, Julian] Canc Res UK London Res Inst, Signal Transduct Lab, London WC2A 3LY, England.
[Jiang, Ming; Saunders, Rebecca E.] Canc Res UK London Res Inst, High Throughput Screening Lab, London WC2A 3LY, England.
[Downward, Julian] Inst Canc Res, London SW3 6JB, England.
[Melnick, Mary Ann; Gettinger, Scott; Walther, Zenta; Wurtz, Anna; Politi, Katerina] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA.
[Gettinger, Scott; Politi, Katerina] Yale Univ, Sch Med, Dept Med Med Oncol, New Haven, CT USA.
[Walther, Zenta; Politi, Katerina] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Gong, Yixuan; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Varmus, Harold] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Heynen, Guus J.; Bernards, Rene] Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands.
[Heideman, Danielle A. M.] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Smit, Egbert F.] Vrije Univ Amsterdam Med Ctr, Div Pulm Dis, Amsterdam, Netherlands.
[Gomez-Roman, Javier] Univ Marques Valdecilla, IFIMAV, Pathol Serv, Santander, Spain.
[Garcia-Castano, Almudena] Univ Marques Valdecilla, IFIMAV, Oncol Serv Hosp, Santander, Spain.
RP Downward, J (reprint author), Canc Res UK London Res Inst, 44 Lincolns Inn Fields, London WC2A 3LY, England.
EM katerina.politi@yale.edu; downward@cancer.org.uk
OI Gomez-Roman, Jose Javier/0000-0002-2849-9435; Bernards,
Rene/0000-0001-8677-3423
FU KWF (Dutch Cancer Society) fellowship; European Commission's Seventh
Framework Programme (FP7) [259770]; National Cancer Institute, NIH [R00
CA131488, R01 CA120247, P01 CA129243]; Pilot grant from the Section of
Medical Oncology, Yale University School of Medicine; Cancer Research UK
FX E.C. de Bruin was financially supported by a KWF (Dutch Cancer Society)
fellowship and has received funding from the European Commission's
Seventh Framework Programme (FP7/2007-2013) under the grant agreement
Lungtarget (project 259770). This work was supported by grants R00
CA131488 (to K. Politi), R01 CA120247 (to K. Politi), and P01 CA129243
(to M. Ladanyi) from the National Cancer Institute, NIH; a Pilot grant
from the Section of Medical Oncology, Yale University School of Medicine
(to S. Gettinger and K. Politi); and was financially supported by Cancer
Research UK.
NR 46
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U1 0
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD MAY
PY 2014
VL 4
IS 5
BP 606
EP 619
DI 10.1158/2159-8290.CD-13-0741
PG 14
WC Oncology
SC Oncology
GA AH1ZA
UT WOS:000335919200030
PM 24535670
ER
PT J
AU Linden, KG
Leachman, SA
Zager, JS
Jakowatz, JG
Viner, JL
McLaren, CE
Barr, RJ
Carpenter, PM
Chen, WP
Elmets, CA
Tangrea, JA
Lim, SJ
Cochran, AJ
Meyskens, FL
AF Linden, Kenneth G.
Leachman, Sancy A.
Zager, Jonathan S.
Jakowatz, James G.
Viner, Jaye L.
McLaren, Christine E.
Barr, Ronald J.
Carpenter, Philip M.
Chen, Wen-Pin
Elmets, Craig A.
Tangrea, Joseph A.
Lim, Sung-Jig
Cochran, Alistair J.
Meyskens, Frank L., Jr.
TI A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial
of Lovastatin for Various Endpoints of Melanoma Pathobiology
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID PROLIFERATIVE ACTIVITY; MELANOCYTIC LESIONS; MALIGNANT-MELANOMA; STATIN
THERAPY; RISK; SKIN; EXPRESSION; KI-67; NEVI; METAANALYSIS
AB On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed.
C1 [Linden, Kenneth G.; Jakowatz, James G.; McLaren, Christine E.; Carpenter, Philip M.; Chen, Wen-Pin; Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA.
[Linden, Kenneth G.; Barr, Ronald J.] Univ Calif Irvine, Dept Dermatol, Orange, CA 92868 USA.
[McLaren, Christine E.] Univ Calif Irvine, Dept Epidemiol, Orange, CA 92868 USA.
[Carpenter, Philip M.] Univ Calif Irvine, Dept Pathol, Orange, CA 92868 USA.
[Cochran, Alistair J.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Leachman, Sancy A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Zager, Jonathan S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Viner, Jaye L.] Takeda Cambridge USA, Cambridge, MA USA.
[Elmets, Craig A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Tangrea, Joseph A.] NCI, Canc Prevent Div, Rockville, MD USA.
[Lim, Sung-Jig] Kyung Hee Univ, Seoul, South Korea.
RP Linden, KG (reprint author), Univ Calif Irvine, Med Ctr, Dept Dermatol, Chao Family Comprehens Canc Ctr, 101 City Dr, Orange, CA 92868 USA.
EM kglinden@uci.edu
FU [CN-35160]; [P30 CA-62203]
FX This study was supported in part by NO-1 CN-35160 and P30 CA-62203 (to
F.L. Meyskens Jr.).
NR 30
TC 4
Z9 4
U1 0
U2 3
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 MAY
PY 2014
VL 7
IS 5
BP 496
EP 504
DI 10.1158/1940-6207.CAPR-13-0189
PG 9
WC Oncology
SC Oncology
GA AH1YH
UT WOS:000335917300003
PM 24614012
ER
PT J
AU Hamilton, DH
Huang, B
Fernando, RI
Tsang, KY
Palena, C
AF Hamilton, Duane H.
Huang, Bruce
Fernando, Romaine I.
Tsang, Kwong-Yok
Palena, Claudia
TI WEE1 Inhibition Alleviates Resistance to Immune Attack of Tumor Cells
Undergoing Epithelial-Mesenchymal Transition
SO CANCER RESEARCH
LA English
DT Article
ID TRANSCRIPTION FACTOR BRACHYURY; HUMAN CARCINOMA-CELLS; T-LYMPHOCYTE
EPITOPE; NUCLEAR LAMINA; CANCER-CELLS; LUNG-CANCER; CDC2 KINASE;
PHOSPHORYLATION; ANTIGEN; APOPTOSIS
AB Aberrant expression of the T-box transcription factor brachyury in human carcinomas drives the phenomenon of epithelial-mesenchymal transition (EMT), a phenotypic modulation that facilitates tumor dissemination and resistance to conventional therapies, including chemotherapy and radiotherapy. By generating isogenic cancer cell lines with various levels of brachyury expression, we demonstrate that high levels of brachyury also significantly reduce the susceptibility of cancer cells to lysis by both antigen-specific T cells and natural killer cells. Our results indicated that resistance of brachyury-high tumor cells to immune-mediated attack was due to inefficient caspase-dependent apoptosis, manifested as inefficient nuclear lamin degradation in the presence of activated effector caspases. We correlated this phenomenon with loss of cell-cycle-dependent kinase 1 (CDK1), which mediates lamin phosphorylation. In support of a causal connection, pretreatment of tumor cells with a specific inhibitor of WEE1, a negative regulator kinase of CDK1, could counter the defective apoptosis of tumor cells expressing high levels of brachyury. Thus, our findings suggested that reconstituting CDK1 activity to threshold levels may be sufficient to restore immunosurveillance of mesenchymal-like cancer cells that have escaped previous immune detection or eradication.
C1 [Hamilton, Duane H.; Huang, Bruce; Fernando, Romaine I.; Tsang, Kwong-Yok; Palena, Claudia] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Palena, C (reprint author), NCI, NIH, 10 Ctr Dr,Room 8B14, Bethesda, MD 20892 USA.
EM palenac@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, NIH.
NR 38
TC 15
Z9 16
U1 1
U2 9
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 MAY 1
PY 2014
VL 74
IS 9
BP 2510
EP 2519
DI 10.1158/0008-5472.CAN-13-1894
PG 10
WC Oncology
SC Oncology
GA AH1ZH
UT WOS:000335920000014
PM 24626094
ER
PT J
AU Fiskus, W
Saba, N
Shen, M
Ghias, M
Liu, JY
Das Gupta, S
Chauhan, L
Rao, R
Gunewardena, S
Schorno, K
Austin, CP
Maddocks, K
Byrd, J
Melnick, A
Huang, P
Wiestner, A
Bhalla, KN
AF Fiskus, Warren
Saba, Nakhle
Shen, Min
Ghias, Mondana
Liu, Jinyun
Das Gupta, Soumyasri
Chauhan, Lata
Rao, Rekha
Gunewardena, Sumedha
Schorno, Kevin
Austin, Christopher P.
Maddocks, Kami
Byrd, John
Melnick, Ari
Huang, Peng
Wiestner, Adrian
Bhalla, Kapil N.
TI Auranofin Induces Lethal Oxidative and Endoplasmic Reticulum Stress and
Exerts Potent Preclinical Activity against Chronic Lymphocytic Leukemia
SO CANCER RESEARCH
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; THIOREDOXIN REDUCTASE; TCL1 EXPRESSION;
CELL-SURVIVAL; CANCER-CELLS; INHIBITION; APOPTOSIS; HSP90; HDAC6;
GLUTATHIONE
AB Chronic lymphocytic leukemia (CLL) exhibits high remission rates after initial chemoimmunotherapy, but with relapses with treatment, refractory disease is the most common outcome, especially in CLL with the deletion of chromosome 11q or 17p. In addressing the need of treatments for relapsed disease, we report the identification of an existing U. S. Food and Drug Administration-approved small-molecule drug to repurpose for CLL treatment. Auranofin ( Ridaura) is approved for use in treating rheumatoid arthritis, but it exhibited preclinical efficacy in CLL cells. By inhibiting thioredoxin reductase activity and increasing intracellular reactive oxygen species levels, auranofin induced a lethal endoplasmic reticulum stress response in cultured and primary CLL cells. In addition, auranofin displayed synergistic lethality with heme oxygenase-1 and glutamate-cysteine ligase inhibitors against CLL cells. Auranofin overcame apoptosis resistance mediated by protective stromal cells, and it also killed primary CLL cells with deletion of chromosome 11q or 17p. In TCL-1 transgenic mice, an in vivo model of CLL, auranofin treatment markedly reduced tumor cell burden and improved mouse survival. Our results provide a rationale to reposition the approved drug auranofin for clinical evaluation in the therapy of CLL.
C1 [Fiskus, Warren; Bhalla, Kapil N.] Houston Methodist Res Inst, Houston, TX 77030 USA.
[Liu, Jinyun; Huang, Peng] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Saba, Nakhle; Ghias, Mondana; Wiestner, Adrian] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Shen, Min] Natl Ctr Adv Translat Sci, NIH, Bethesda, MD USA.
[Das Gupta, Soumyasri; Chauhan, Lata; Rao, Rekha; Gunewardena, Sumedha] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Schorno, Kevin] Univ Kansas, Inst Adv Med Innovat, Kansas City, KS USA.
[Maddocks, Kami; Byrd, John] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Div Hematol, Columbus, OH 43210 USA.
[Melnick, Ari] Weill Cornell Med Coll, New York, NY USA.
RP Bhalla, KN (reprint author), Houston Methodist Res Inst, 6670 Bertner Ave,R9-113, Houston, TX 77030 USA.
EM knbhalla@tmhs.org
FU NCI NIH HHS [P01 CA081534, P30 CA016672, R01 CA085563, R01 CA100428]
NR 48
TC 43
Z9 43
U1 3
U2 24
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD MAY 1
PY 2014
VL 74
IS 9
BP 2520
EP 2532
DI 10.1158/0008-5472.CAN-13-2033
PG 13
WC Oncology
SC Oncology
GA AH1ZH
UT WOS:000335920000015
PM 24599128
ER
PT J
AU Hofmann, JN
Hosgood, HD
Liu, CS
Chow, WH
Shuch, B
Cheng, WL
Lin, TT
Moore, LE
Lan, Q
Rothman, N
Purdue, MP
AF Hofmann, Jonathan N.
Hosgood, H. Dean, III
Liu, Chin-San
Chow, Wong-Ho
Shuch, Brian
Cheng, Wen-Ling
Lin, Ta-Tsung
Moore, Lee E.
Lan, Qing
Rothman, Nathaniel
Purdue, Mark P.
TI A nested case-control study of leukocyte mitochondrial DNA copy number
and renal cell carcinoma in the Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial
SO CARCINOGENESIS
LA English
DT Article
ID OXIDATIVE STRESS; RISK
AB This study reports the first prospective evidence that high leukocyte mtDNA copy number is associated with increased future risk of RCC, suggesting that oxidative DNA damage and mitochondrial dysfunction may contribute to renal carcinogenesis.Mitochondrial DNA (mtDNA) is vulnerable to mutations, and the number of copies of mtDNA per cell may increase to compensate for DNA damage. Case-control studies have reported associations between altered mtDNA copy number and risk of renal cell carcinoma (RCC); however, this association has not been investigated prospectively. We conducted a nested case-control study (252 cases and 504 controls) of RCC risk in relation to pre-diagnostic leukocyte mtDNA copy number in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. mtDNA copy number was measured in triplicate using a fluorescence-based quantitative PCR assay; samples from 22 cases and 36 controls could not be assayed, leaving 230 cases and 468 controls for analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. High mtDNA copy number was associated with an increased risk of RCC, both overall (highest quartile versus lowest: OR = 2.0, 95% CI = 1.2-3.2; P (trend) = 0.002) and among cases diagnosed a parts per thousand yen6 years after blood collection (OR = 2.6, 95% CI = 1.4-5.0; P (trend) = 0.003). These findings did not differ significantly by sex, body mass index, history of hypertension or smoking status (P (interaction) a parts per thousand yen 0.3). Results of this study suggest that high pre-diagnostic leukocyte mtDNA copy number, a suspected marker of oxidative DNA damage and mitochondrial dysfunction, is associated with increased future RCC risk.
C1 [Hofmann, Jonathan N.; Moore, Lee E.; Lan, Qing; Rothman, Nathaniel; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Div Epidemiol, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Liu, Chin-San; Cheng, Wen-Ling; Lin, Ta-Tsung] Changhua Christian Hosp, Vasc & Genom Res Ctr, Changhua 500, Taiwan.
[Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Shuch, Brian] Yale Univ, Sch Med, Dept Urol, New Haven, CT 06520 USA.
RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E132,MSC 9771, Bethesda, MD 20892 USA.
EM hofmannjn@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU Intramural Research Program of the National Cancer Institute; Division
of Cancer Prevention; National Cancer Institute; National Institutes of
Health; Department of Health and Human Services
FX Intramural Research Program of the National Cancer Institute and
contracts from the Division of Cancer Prevention, National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services.
NR 17
TC 11
Z9 12
U1 0
U2 8
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 MAY
PY 2014
VL 35
IS 5
BP 1028
EP 1031
DI 10.1093/carcin/bgt495
PG 4
WC Oncology
SC Oncology
GA AH3RW
UT WOS:000336043800008
PM 24398668
ER
PT J
AU Bode, C
Kinjo, T
Alvord, WG
Klinman, DM
AF Bode, Christian
Kinjo, Takeshi
Alvord, W. Gregory
Klinman, Dennis M.
TI Suppressive oligodeoxynucleotides reduce lung cancer susceptibility in
mice with silicosis
SO CARCINOGENESIS
LA English
DT Article
ID A/J MICE; CYCLOOXYGENASE-2 INHIBITOR; CHEMOPREVENTIVE ACTIVITY; IMMUNE
ACTIVATION; INDUCED ARTHRITIS; TUMOR PROMOTION; TTAGGG MOTIFS; MOUSE
SKIN; INFLAMMATION; CARCINOGENESIS
AB Using a novel murine model, we demonstrate that silicotic inflammation increases susceptibility to lung cancer initiated by exposure to NNK, a potent carcinogen in cigarettes. Cancer susceptibility is reduced to background by blocking this inflammation through treatment with immunosuppressive oligonucleotides.Silicosis is an inflammatory lung disease induced by the inhalation of silica-containing dust particles. There is conflicting data on whether patients with silicosis are more susceptible to lung cancer induced by cigarette smoke. To examine this issue experimentally, a model was developed in which one of the most abundant and potent carcinogens present in cigarette smoke [4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)] was administered to mice at the peak of silica-induced pulmonary inflammation. Results show that the incidence of lung tumors in silicotic mice treated with NNK was significantly increased compared with mice exposed to silica or NNK alone. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs can block pathologic inflammation. We therefore examined whether treatment with these suppressive (Sup) ODN could block silica-induced pulmonary inflammation and thereby reduce susceptibility to lung cancer. Results show that Sup (but not control) ODN inhibit pulmonary fibrosis and other inflammatory manifestations of chronic silicosis. Of greater import, Sup ODN reduced lung tumor incidence and multiplicity in silicotic mice exposed to NNK. These findings establish an experimental model for examining the role of silicotic inflammation in cancer susceptibility and demonstrate that Sup ODN represent a novel therapy for chronic silicosis.
C1 [Bode, Christian; Kinjo, Takeshi; Klinman, Dennis M.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Bode, Christian] Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany.
[Kinjo, Takeshi] Univ Ryukyus, Dept Med, Nishihara, Okinawa 90301, Japan.
[Alvord, W. Gregory] NCI, DMS Appl Informat & Management Sci, Frederick, MD 21702 USA.
RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM klinmand@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 57
TC 3
Z9 3
U1 0
U2 5
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 MAY
PY 2014
VL 35
IS 5
BP 1078
EP 1083
DI 10.1093/carcin/bgu005
PG 6
WC Oncology
SC Oncology
GA AH3RW
UT WOS:000336043800014
PM 24403310
ER
PT J
AU Wu, LS
Jiang, H
Chawsheen, HA
Mishra, M
Young, MR
Gerard, M
Toledano, MB
Colburn, NH
Wei, Q
AF Wu, Lisha
Jiang, Hong
Chawsheen, Hedy A.
Mishra, Murli
Young, Matthew R.
Gerard, Matthieu
Toledano, Michel B.
Colburn, Nancy H.
Wei, Qiou
TI Tumor promoter-induced sulfiredoxin is required for mouse skin
tumorigenesis
SO CARCINOGENESIS
LA English
DT Article
ID SULFINIC ACID REDUCTASE; HUMAN LUNG-CANCER; SACCHAROMYCES-CEREVISIAE;
TRANSCRIPTION FACTORS; 2-CYS PEROXIREDOXIN; CELL-PROLIFERATION;
GENE-EXPRESSION; DUAL FUNCTIONS; TARGET GENE; NRF2
AB Srx induced by tumor promoter reduces hyperoxidized Prxs, increases cells' ability to survive through oxidative stress by inhibition of TPA-induced apoptosis and facilitates skin tumor development.Sulfiredoxin (Srx), the exclusive enzyme that reduces the hyperoxidized inactive form of peroxiredoxins (Prxs), has been found highly expressed in several types of human skin cancer. To determine whether Srx contributed to skin tumorigenesis in vivo, Srx null mice were generated on an FVB background. Mouse skin tumorigenesis was induced by a 7,12-dimethylbenz[alpha]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) protocol. We found that the number, volume and size of papillomas in Srx(-/-) mice were significantly fewer compared with either wild-type (Wt) or heterozygous (Het) siblings. Histopathological analysis revealed more apoptotic cells in tumors from Srx(-/-) mice. Mechanistic studies in cell culture revealed that Srx was stimulated by TPA in a redox-independent manner. This effect was mediated transcriptionally through the activation of mitogen-activated protein kinase and Jun-N-terminal kinase. We also demonstrated that Srx was capable of reducing hyperoxidized Prxs to facilitate cell survival under oxidative stress conditions. These findings suggested that loss of Srx protected mice, at least partially, from DMBA/TPA-induced skin tumorigenesis. Therefore, Srx has an oncogenic role in skin tumorigenesis and targeting Srx may provide novel strategies for skin cancer prevention or treatment.
C1 [Wu, Lisha; Jiang, Hong; Chawsheen, Hedy A.; Mishra, Murli; Wei, Qiou] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA.
[Wu, Lisha; Jiang, Hong; Wei, Qiou] Univ Kentucky, Markey Canc Ctr, Lexington, KY 40536 USA.
[Young, Matthew R.; Colburn, Nancy H.] Ctr Canc Res, Lab Canc Prevent, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Gerard, Matthieu] CEA Saclay, Epigenet Regulat & Canc Grp, Inst Biol & Technol Saclay, F-91191 Gif Sur Yvette, France.
[Toledano, Michel B.] CEA Saclay, Oxidat Stress & Canc Grp, Inst Biol & Technol Saclay, F-91191 Gif Sur Yvette, France.
RP Wei, Q (reprint author), Univ Kentucky, Grad Ctr Toxicol, 1095 VA Dr,140 HSRB, Lexington, KY 40513 USA.
EM qiou.wei@uky.edu
RI Mishra, Murli/A-8998-2013;
OI Mishra, Murli/0000-0003-3477-0081; GERARD, Matthieu/0000-0001-8956-0597
FU National Cancer Institute, National Institutes of Health [R00CA149144]
FX National Cancer Institute, National Institutes of Health (R00CA149144 to
Q.W.).
NR 44
TC 6
Z9 7
U1 0
U2 0
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 MAY
PY 2014
VL 35
IS 5
BP 1177
EP 1184
DI 10.1093/carcin/bgu035
PG 8
WC Oncology
SC Oncology
GA AH3RW
UT WOS:000336043800025
PM 24503444
ER
PT J
AU Hernandez-Ramon, EE
Sandoval, NA
John, K
Cline, JM
Wood, CE
Woodward, RA
Poirier, MC
AF Hernandez-Ramon, Elena E.
Sandoval, Nicole A.
John, Kaarthik
Cline, J. Mark
Wood, Charles E.
Woodward, Ruth A.
Poirier, Miriam C.
TI Tamoxifen-DNA adduct formation in monkey and human reproductive organs
SO CARCINOGENESIS
LA English
DT Article
ID REVERSE-TRANSCRIPTASE INHIBITORS; BREAST-CANCER; MITOCHONDRIAL
COMPROMISE; HUMAN ENDOMETRIUM; MASS-SPECTROMETRY; WOMEN; RAT;
GENOTOXICITY; CARCINOGEN; EXPOSURE
AB The estrogen analog tamoxifen (TAM), used for adjuvant therapy of breast cancer, induces endometrial and uterine tumors in breast cancer patients. Proliferation stimulus of the uterine endometrium is likely involved in tumor induction, but genotoxicity may also play a role. Formation of TAM-DNA adducts in human tissues has been reported but remains controversial. To address this issue, we examined TAM-DNA adducts in uteri from two species of monkeys, Erythrocebus patas (patas) and Macaca fascicularis (macaque), and in human endometrium and myometrium. Monkeys were given 3-4 months of chronic TAM dosing scaled to be equivalent to the daily human dose. In the uteri, livers and brains from the patas (n = 3), and endometrium from the macaques (n = 4), TAM-DNA adducts were measurable by TAM-DNA chemiluminescence immunoassay. Average TAM-DNA adduct values for the patas uteri (23 adducts/10(8) nucleotides) were similar to those found in endometrium of the macaques (19 adducts/10(8) nucleotides). Endometrium of macaques exposed to both TAM and low-dose estradiol (n = 5) averaged 34 adducts/10(8) nucleotides. To examine TAM-DNA persistence in the patas, females (n = 3) were exposed to TAM for 3 months and to no drug for an additional month, resulting in low or non-detectable TAM-DNA in livers and uteri. Human endometrial and myometrial samples from women receiving (n = 8) and not receiving (n = 8) TAM therapy were also evaluated. Women receiving TAM therapy averaged 10.3 TAM-DNA adducts/10(8) nucleotides, whereas unexposed women showed no detectable TAM-DNA. The data indicate that genotoxicity, in addition to estrogen agonist effects, may contribute to TAM-induced human endometrial cancer.We examined TAM-DNA adducts in two species of monkeys and in humans treated with TAM. Our data showed that adducts are formed in uterine tissue in monkeys and humans, suggesting a role of TAM genotoxicity in endometrial cancer.
C1 [Hernandez-Ramon, Elena E.; Sandoval, Nicole A.; John, Kaarthik; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA.
[Cline, J. Mark; Wood, Charles E.] Wake Forest Sch Med, Dept Pathol, Winston Salem, NC 27157 USA.
[Woodward, Ruth A.] NICHD, Res Anim Management Branch, Shared Anim Facil, NIH, Dickerson, MD 20837 USA.
RP Hernandez-Ramon, EE (reprint author), NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bldg 37,Room 4032,NIH 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA.
EM elena.hernandez-ramon@nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health.
NR 32
TC 2
Z9 2
U1 2
U2 3
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 MAY
PY 2014
VL 35
IS 5
DI 10.1093/carcin/bgu029
PG 5
WC Oncology
SC Oncology
GA AH3RW
UT WOS:000336043800024
PM 24501327
ER
PT J
AU Fox, D
Yan, ZJ
Ling, C
Zhao, Y
Lee, DY
Fukagawa, T
Yang, W
Wang, WD
AF Fox, David, III
Yan, Zhijiang
Ling, Chen
Zhao, Ye
Lee, Duck-Yeon
Fukagawa, Tatsuo
Yang, Wei
Wang, Weidong
TI The histone-fold complex MHF is remodeled by FANCM to recognize branched
DNA and protect genome stability
SO CELL RESEARCH
LA English
DT Article
DE FANCM; Fanconi anemia; MHF; histone-fold; genome stability; branched DNA
ID STALLED REPLICATION FORKS; COMPLEMENTATION GROUP-M; ANEMIA CORE COMPLEX;
CROSS-LINK REPAIR; OUTER KINETOCHORE; DATA-BANK; ORTHOLOG; PATHWAY;
MONOUBIQUITINATION; IDENTIFICATION
AB Histone-fold proteins typically assemble in multiprotein complexes to bind duplex DNA. However, one histone-fold complex, MHF, associates with Fanconi anemia (FA) protein FANCM to form a branched DNA remodeling complex that senses and repairs stalled replication forks and activates FA DNA damage response network. How the FANCM-MHF complex recognizes branched DNA is unclear. Here, we solved the crystal structure of MHF and its complex with the MHF-interaction domain (referred to as MID) of FANCM, and performed structure-guided mutagenesis. We found that the MID-MHF complex consists of one histone H3-H4-like MHF heterotetramer wrapped by a single polypeptide of MID. We identified a zinc atom-liganding structure at the central interface between MID and MHF that is critical for stabilization of the complex. Notably, the DNA-binding surface of MHF was altered by MID in both electrostatic charges and allosteric conformation. This leads to a switch in the DNA-binding preference - from duplex DNA by MHF alone, to branched DNA by the MID-MHF complex. Mutations that disrupt either the composite DNA-binding surface or the protein-protein interface of the MID-MHF complex impaired activation of the FA network and genome stability. Our data provide the structural basis of how FANCM and MHF work together to recognize branched DNA, and suggest a novel mechanism by which histone-fold complexes can be remodeled by their partners to bind special DNA structures generated during DNA metabolism.
C1 [Fox, David, III; Yan, Zhijiang; Ling, Chen; Wang, Weidong] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Zhao, Ye; Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Duck-Yeon] NHLBI, Biochem Core Facil, NIH, Bethesda, MD 20892 USA.
[Fukagawa, Tatsuo] Natl Inst Genet, Dept Mol Genet, Mishima, Shizuoka 4118540, Japan.
[Fukagawa, Tatsuo] Grad Univ Adv Studies, Mishima, Shizuoka 4118540, Japan.
RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
EM wangw@grc.nia.nih.gov
RI Zhao, Ye/I-2936-2014; Yang, Wei/D-4926-2011
OI Zhao, Ye/0000-0002-5455-2586; Yang, Wei/0000-0002-3591-2195
FU Intramural Research Program of the National Institute on Aging, National
Institute of Health [AG000688-07]; Ministry of Education, Culture,
Sports, Science and Technology (MEXT) of Japan
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging (AG000688-07), National Institute of
Health; and by a Grant-in-Aid for Scientific Research (S) from the
Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan to TF.
NR 43
TC 7
Z9 7
U1 0
U2 12
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD MAY
PY 2014
VL 24
IS 5
BP 560
EP 575
DI 10.1038/cr.2014.42
PG 16
WC Cell Biology
SC Cell Biology
GA AH1XI
UT WOS:000335914700005
PM 24699063
ER
PT J
AU Xu, XH
Deng, CY
Liu, Y
He, M
Peng, J
Wang, T
Yuan, L
Zheng, ZS
Blackshear, PJ
Luo, ZG
AF Xu, Xiao-Hui
Deng, Cai-Yun
Liu, Yang
He, Miao
Peng, Jian
Wang, Tong
Yuan, Lei
Zheng, Zhi-Sheng
Blackshear, Perry J.
Luo, Zhen-Ge
TI MARCKS regulates membrane targeting of Rab10 vesicles to promote axon
development
SO CELL RESEARCH
LA English
DT Article
DE MARCKS; Rab10; plasmalemmal precursor vesicles; axon growth
ID PROTEIN-KINASE-C; MAJOR SPECIFIC SUBSTRATE; NEURONAL POLARIZATION;
PLASMA-MEMBRANE; ANTEROGRADE TRANSPORT; IN-VIVO; PHOSPHORYLATION; BRAIN;
GROWTH; CELLS
AB Axon development requires membrane addition from the intracellular supply, which has been shown to be mediated by Rab10-positive plasmalemmal precursor vesicles (PPVs). However, the molecular mechanisms underlying the membrane trafficking processes of PPVs remain unclear. Here, we show that myristoylated alanine-rich C-kinase substrate (MARCKS) mediates membrane targeting of Rab10-positive PPVs, and this regulation is critical for axon development. We found that the GTP-locked active form of Rab10 binds to membrane-associated MARCKS, whose affinity depends on the phosphorylation status of the MARCKS effector domain. Either genetic silencing of MARCKS or disruption of its interaction with Rab10 inhibited axon growth of cortical neurons, impaired docking and fusion of Rab10 vesicles with the plasma membrane, and consequently caused a loss of membrane insertion of axonal receptors responsive to extracellular axon growth factors. Thus, this study has identified a novel function of MARCKS in mediating membrane targeting of PPVs during axon development.
C1 [Xu, Xiao-Hui; Deng, Cai-Yun; Liu, Yang; He, Miao; Peng, Jian; Wang, Tong; Yuan, Lei; Zheng, Zhi-Sheng; Luo, Zhen-Ge] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China.
[Xu, Xiao-Hui; Deng, Cai-Yun; Liu, Yang; He, Miao; Peng, Jian; Wang, Tong; Yuan, Lei; Zheng, Zhi-Sheng; Luo, Zhen-Ge] Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.
[Xu, Xiao-Hui] Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China.
[Peng, Jian] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China.
[Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Luo, ZG (reprint author), Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China.
EM zgluo@ion.ac.cn
RI Wang, Tong/O-7351-2015
OI Wang, Tong/0000-0002-3680-8189
FU National Natural Science Foundation of China [31330032, 31321091,
61327902, 81171190]; National Key Basic Research Program of China
[2014CB910203]; SA-SIBS Scholarship Program; Shanghai Postdoctoral
Scientific Program; China Postdoctoral Science Foundation; KC Wong
Education Foundation
FX This work was supported by the National Natural Science Foundation of
China (31330032, 31321091, and 61327902 to ZG L and 81171190 to XH X)
and the National Key Basic Research Program of China (2014CB910203). We
thank Dr Q Hu of ION Imaging Facility with microscope analysis and Dr Y
Kong with EM analysis. XH X was supported by SA-SIBS Scholarship
Program, Shanghai Postdoctoral Scientific Program, China Postdoctoral
Science Foundation funded Project, and KC Wong Education Foundation.
NR 58
TC 11
Z9 12
U1 4
U2 24
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD MAY
PY 2014
VL 24
IS 5
BP 576
EP 594
DI 10.1038/cr.2014.33
PG 19
WC Cell Biology
SC Cell Biology
GA AH1XI
UT WOS:000335914700006
PM 24662485
ER
PT J
AU van Schaijk, BCL
Kumar, TRS
Vos, MW
Richman, A
van Gemert, GJ
Li, T
Eappen, AG
Williamson, KC
Morahan, BJ
Fishbaugher, M
Kennedy, M
Camargo, N
Khan, SM
Janse, CJ
Sim, KL
Hoffman, SL
Kappe, SHI
Sauerwein, RW
Fidock, DA
Vaughan, AM
AF van Schaijk, Ben C. L.
Kumar, T. R. Santha
Vos, Martijn W.
Richman, Adam
van Gemert, Geert-Jan
Li, Tao
Eappen, Abraham G.
Williamson, Kim C.
Morahan, Belinda J.
Fishbaugher, Matt
Kennedy, Mark
Camargo, Nelly
Khan, Shahid M.
Janse, Chris J.
Sim, Kim Lee
Hoffman, Stephen L.
Kappe, Stefan H. I.
Sauerwein, Robert W.
Fidock, David A.
Vaughan, Ashley M.
TI Type II Fatty Acid Biosynthesis Is Essential for Plasmodium falciparum
Sporozoite Development in the Midgut of Anopheles Mosquitoes
SO EUKARYOTIC CELL
LA English
DT Article
ID LIVER-STAGE DEVELOPMENT; TOXOPLASMA-GONDII; MALARIA PARASITES; GENE
DELETION; IN-VITRO; APICOPLAST; GAMETOCYTES; INFECTION; RESISTANCE;
PROTEIN
AB The prodigious rate at which malaria parasites proliferate during asexual blood-stage replication, midgut sporozoite production, and intrahepatic development creates a substantial requirement for essential nutrients, including fatty acids that likely are necessary for parasite membrane formation. Plasmodium parasites obtain fatty acids either by scavenging from the vertebrate host and mosquito vector or by producing fatty acids de novo via the type two fatty acid biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway in Plasmodium falciparum, the species responsible for the most lethal form of human malaria. Using antibodies, we find that the FAS-II enzyme FabI is expressed in mosquito midgut oocysts and sporozoites as well as liver-stage parasites but not during the blood stages. As expected, FabI colocalizes with the apicoplast-targeted acyl carrier protein, indicating that FabI functions in the apicoplast. We further analyze the FAS-II pathway in Plasmodium falciparum by assessing the functional consequences of deleting fabI and fabB/F. Targeted deletion or disruption of these genes in P. falciparum did not affect asexual blood-stage replication or the generation of midgut oocysts; however, subsequent sporozoite development was abolished. We conclude that the P. falciparum FAS-II pathway is essential for sporozoite development within the midgut oocyst. These findings reveal an important distinction from the rodent Plasmodium parasites P. berghei and P. yoelii, where the FAS-II pathway is known to be required for normal parasite progression through the liver stage but is not required for oocyst development in the Anopheles mosquito midgut.
C1 [van Schaijk, Ben C. L.; Vos, Martijn W.; van Gemert, Geert-Jan; Sauerwein, Robert W.] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, NL-6525 ED Nijmegen, Netherlands.
[Kumar, T. R. Santha; Fidock, David A.] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10027 USA.
[Richman, Adam; Li, Tao; Eappen, Abraham G.; Sim, Kim Lee; Hoffman, Stephen L.] Sanaria Inc, Rockville, MD USA.
[Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60626 USA.
[Williamson, Kim C.; Morahan, Belinda J.] NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[Fishbaugher, Matt; Kennedy, Mark; Camargo, Nelly; Kappe, Stefan H. I.; Vaughan, Ashley M.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Khan, Shahid M.; Janse, Chris J.] Leiden Univ, Leiden Malaria Res Grp, Leiden, Netherlands.
[Kappe, Stefan H. I.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Fidock, David A.] Columbia Univ, Coll Phys & Surg, Dept Infect Dis, New York, NY USA.
RP Fidock, DA (reprint author), Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10027 USA.
EM df2260@columbia.edu; ashley.vaughan@seattlebiomed.org
RI Sauerwein, Robert/C-8519-2013
FU NIH [R56 AI080685, R01 AI085584]; Foundation for the National Institutes
of Health through the Grand Challenges in Global Health Initiative
[1481]; Intramural Research Program of the National Institute of Allergy
and Infectious Diseases; National Institutes of Health; Top Institute
Pharma (Netherlands) [T4-102]
FX The NIH (R56 AI080685 to S.H.I.K. and A.M.V. and R01 AI085584 to
D.A.F.), the Foundation for the National Institutes of Health through
the Grand Challenges in Global Health Initiative (grant no. 1481; to
S.H.I.K.), the Intramural Research Program of the National Institute of
Allergy and Infectious Diseases, National Institutes of Health, and Top
Institute Pharma (Netherlands) project T4-102 all provided partial
funding for this work. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 60
TC 22
Z9 22
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1535-9778
EI 1535-9786
J9 EUKARYOT CELL
JI Eukaryot. Cell
PD MAY
PY 2014
VL 13
IS 5
BP 550
EP 559
DI 10.1128/EC.00264-13
PG 10
WC Microbiology; Mycology
SC Microbiology; Mycology
GA AH1UY
UT WOS:000335907900001
PM 24297444
ER
PT J
AU Park, YN
Zhao, XH
Yim, YI
Todor, H
Ellerbrock, R
Reidy, M
Eisenberg, E
Masison, DC
Greene, LE
AF Park, Yang-Nim
Zhao, Xiaohong
Yim, Yang-In
Todor, Horia
Ellerbrock, Robyn
Reidy, Michael
Eisenberg, Evan
Masison, Daniel C.
Greene, Lois E.
TI Hsp104 Overexpression Cures Saccharomyces cerevisiae [PSI+] by Causing
Dissolution of the Prion Seeds
SO EUKARYOTIC CELL
LA English
DT Article
ID GUANIDINE-HYDROCHLORIDE; YEAST PRION; PROTEIN DISAGGREGATION;
GENE-EXPRESSION; IN-VIVO; PROPAGATION; CHAPERONE; HSP70; ELIMINATION;
PSI(+)
AB The [PSI+] yeast prion is formed when Sup35 misfolds into amyloid aggregates. [PSI+], like other yeast prions, is dependent on the molecular chaperone Hsp104, which severs the prion seeds so that they pass on as the yeast cells divide. Surprisingly, however, overexpression of Hsp104 also cures [PSI+]. Several models have been proposed to explain this effect: inhibition of severing, asymmetric segregation of the seeds between mother and daughter cells, and dissolution of the prion seeds. First, we found that neither the kinetics of curing nor the heterogeneity in the distribution of the green fluorescent protein (GFP)-labeled Sup35 foci in partially cured yeast cells is compatible with Hsp104 overexpression curing [PSI+] by inhibiting severing. Second, we ruled out the asymmetric segregation model by showing that the extent of curing was essentially the same in mother and daughter cells and that the fluorescent foci did not distribute asymmetrically, but rather, there was marked loss of foci in both mother and daughter cells. These results suggest that Hsp104 overexpression cures [PSI+] by dissolution of the prion seeds in a two-step process. First, trimming of the prion seeds by Hsp104 reduces their size, and second, their amyloid core is eliminated, most likely by proteolysis.
C1 [Park, Yang-Nim; Zhao, Xiaohong; Yim, Yang-In; Todor, Horia; Ellerbrock, Robyn; Eisenberg, Evan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Reidy, Michael; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM greenel@helix.nih.gov
OI Reidy, Michael/0000-0002-9290-7595
FU Intramural Research Program of the National Institutes of Health (NIH);
National Heart, Lung, and Blood Institute; National Institute of
Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), the National Heart, Lung, and Blood
Institute, and the National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 44
TC 14
Z9 14
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1535-9778
EI 1535-9786
J9 EUKARYOT CELL
JI Eukaryot. Cell
PD MAY
PY 2014
VL 13
IS 5
BP 635
EP 647
DI 10.1128/EC.00300-13
PG 13
WC Microbiology; Mycology
SC Microbiology; Mycology
GA AH1UY
UT WOS:000335907900008
PM 24632242
ER
PT J
AU Olafsdottir, LB
Erlendsdottir, H
Melo-Cristino, J
Weinberger, DM
Ramirez, M
Kristinsson, KG
Gottfredsson, M
AF Olafsdottir, L. B.
Erlendsdottir, H.
Melo-Cristino, J.
Weinberger, D. M.
Ramirez, M.
Kristinsson, K. G.
Gottfredsson, M.
TI Invasive infections due to Streptococcus pyogenes: seasonal variation of
severity and clinical characteristics, Iceland, 1975 to 2012
SO EUROSURVEILLANCE
LA English
DT Article
ID GROUP-A STREPTOCOCCI; UNITED-STATES; VITAMIN-D; DISEASE; INFLUENZA;
EUROPE; SUSCEPTIBILITY; EPIDEMIOLOGY; CANDIDEMIA; NATIONWIDE
AB Epidemiology and clinical characteristics of invasive Group A streptococcal infections (IGASI) are highly variable. Long-term studies are needed to understand the interplay between epidemiology and virulence. In a population-based study of IGASI in Iceland from 1975 to 2012, 288 cases were identified by positive cultures from normally sterile body sites. Charts were reviewed retrospectively and emm-types of viable Streptococcus pyogenes isolates (n=226) determined. Comparing the first and last decade of the study period, IGASI incidence increased from 1.09 to 3.96 cases per 100,000 inhabitants per year. The most common were emm types 1 (25%), 28 (11%) and 89 (11%); emm1 strains were most likely to cause severe infections. Infections in adults were significantly more likely to be severe during the seasonal peak from January to April (risk ratio: 2.36, 95% confidence interval: 1.34-4.15). Significant seasonal variability in severity was noted among patients with diagnosis of sepsis, respiratory infection and cellulitis, with 38% of severe infections in January to April compared with 16% in other months (p < 0.01). A seasonal increase in severity of IGASI suggested that generalised seasonal increase in host susceptibility, rather than introduction of more virulent strains may play a role in the pathogenesis of these potentially fatal infections.
C1 [Olafsdottir, L. B.; Gottfredsson, M.] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
[Erlendsdottir, H.; Kristinsson, K. G.] Landspitali Univ Hosp, Reykjavik, Iceland.
[Erlendsdottir, H.; Kristinsson, K. G.; Gottfredsson, M.] Univ Iceland, Fac Med, Sch Hlth Sci, Reykjavik, Iceland.
[Melo-Cristino, J.; Ramirez, M.] Univ Lisbon, Fac Med, Inst Mol Med, Inst Microbiol, P-1699 Lisbon, Portugal.
[Weinberger, D. M.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Weinberger, D. M.] Yale Univ, Dept Epidemiol Microbial Dis, Sch Publ Hlth, New Haven, CT USA.
RP Olafsdottir, LB (reprint author), Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
RI Ramirez, Mario/B-4993-2008; Melo-Cristino, Jose/H-3726-2013;
OI Ramirez, Mario/0000-0002-4084-6233; Melo-Cristino,
Jose/0000-0001-8643-1722; Gottfredsson, Magnus/0000-0003-2465-0422
FU Icelandic Center for Research, Rannis [100436021]; Landspitali
University Hospital Science Fund
FX This work was supported in part by grants from the Icelandic Center for
Research, Rannis [grant number 100436021]; and the Landspitali
University Hospital Science Fund (http://rannis.is/english/home/). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. This study was
presented in part at ID week, San Diego, 17-21 October 2012.
NR 34
TC 6
Z9 6
U1 0
U2 1
PU EUR CENTRE DIS PREVENTION & CONTROL
PI STOCKHOLM
PA TOMTEBODAVAGEN 11A, STOCKHOLM, 171 83, SWEDEN
SN 1560-7917
J9 EUROSURVEILLANCE
JI Eurosurveillance
PD MAY 1
PY 2014
VL 19
IS 17
BP 5
EP 14
AR 20784
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA AH1WX
UT WOS:000335913600002
PM 24821122
ER
PT J
AU James, P
Berrigan, D
Hart, JE
Hipp, JA
Hoehner, CM
Kerr, J
Major, JM
Oka, M
Laden, F
AF James, Peter
Berrigan, David
Hart, Jaime E.
Hipp, J. Aaron
Hoehner, Christine M.
Kerr, Jacqueline
Major, Jacqueline M.
Oka, Masayoshi
Laden, Francine
TI Effects of buffer size and shape on associations between the built
environment and energy balance
SO HEALTH & PLACE
LA English
DT Article
DE Built environment; Walking; Body mass index; Geographic information
systems; Spatial uncertainty
ID AREAL UNIT PROBLEM; BODY-MASS INDEX; PHYSICAL-ACTIVITY; URBAN FORM;
NEIGHBORHOOD BOUNDARIES; FOOD ENVIRONMENT; WOMENS HEALTH; RISK-FACTORS;
ZONE DESIGN; OBESITY
AB Uncertainty in the relevant spatial context may drive heterogeneity in findings on the built environment and energy balance. To estimate the effect of this uncertainty, we conducted a sensitivity analysis defining intersection and business densities and counts within different buffer sizes and shapes on associations with self-reported walking and body mass index. Linear regression results indicated that the scale and shape of buffers influenced study results and may partly explain the inconsistent findings in the built environment and energy balance literature. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [James, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Berrigan, David] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Hart, Jaime E.] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02215 USA.
[Hart, Jaime E.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Hipp, J. Aaron] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA.
[Hoehner, Christine M.] Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63110 USA.
[Kerr, Jacqueline] UCSD, Dept Psychol, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Kerr, Jacqueline] SDSU, Grad Sch Publ Hlth, La Jolla, CA 92093 USA.
[Major, Jacqueline M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Oka, Masayoshi] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02215 USA.
RP James, P (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 401 Pk Dr,3rd Floor West, Boston, MA 02215 USA.
EM pjames@hsph.harvard.edu; berrigad@mail.nih.gov;
rejch@channing.harvard.edu; ahipp@brownschool.wustl.edu;
hoehnerc@wudosis.wustl.edu; jkerr@ucsd.edu; jqmajor@yahoo.com;
moka@wudosis.wustl.edu; francine.laden@channing.harvard.edu
FU NCI Centers for Transdisciplinary Research on Energetics and Cancer
(TREC) [U54 CA155626, U54 CA155435, U54 CA155850, U54 CA155796, U01
CA116850]; NCI as part of the TREC initiative; Harvard NHLBI
Cardiovascular Epidemiology Training Grant [T32 HL 098048]; NIH [UM1
CA176726, R01 ES017017]
FX This work was supported by the NCI Centers for Transdisciplinary
Research on Energetics and Cancer (TREC) (U54 CA155626, U54 CA155435,
U54 CA155850, U54 CA155796, U01 CA116850). All authors were funded by
NCI as part of the TREC initiative (except Berrigan and Major). The
opinions or assertions contained herein are the private ones of the
authors and are not considered as official or reflecting the views of
the National Institutes of Health. Work was also supported by the
Harvard NHLBI Cardiovascular Epidemiology Training Grant T32 HL 098048
and NIH Grants UM1 CA176726 and R01 ES017017. We thank the TREC Spatial
and Contextual Measures and Modeling Working Group who contributed
greatly to this analysis.
NR 59
TC 21
Z9 21
U1 3
U2 15
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 MAY
PY 2014
VL 27
BP 162
EP 170
DI 10.1016/j.healthplace.2014.02.003
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AG9TX
UT WOS:000335763800021
PM 24607875
ER
PT J
AU Cruse, G
Metcalfe, DD
Olivera, A
AF Cruse, Glenn
Metcalfe, Dean D.
Olivera, Ana
TI Functional Deregulation of KIT Link to Mast Cell Proliferative Diseases
and Other Neoplasms
SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Mastocytosis; KIT mutations; KIT signaling; KIT trafficking; KIT
inhibitors
ID RECEPTOR TYROSINE KINASE; GROWTH-FACTOR-RECEPTOR; CHRONIC
MYELOID-LEUKEMIA; MUTANT C-KIT; GENE-EXPRESSION PROFILE; STEM-CELL;
SYSTEMIC MASTOCYTOSIS; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS;
CATALYTIC DOMAIN
AB In-this review, the authors discuss common gain-of-function mutations in the stem cell factor receptor KIT found in mast cell proliferation disorders and summarize the current understanding of the molecular mechanisms by which these transforming mutations may affect KIT structure and function leading to altered downstream signaling and cellular transformation. Drugs targeting KIT have shown mixed success in the treatment of mastocytosis and other hyperproliferative diseases. A brief overview of the most common KIT inhibitors currently used, the reasons for the varied clinical results of such inhibitors and a discussion of potential new strategies are provided.
C1 [Cruse, Glenn; Metcalfe, Dean D.; Olivera, Ana] NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Olivera, A (reprint author), NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, 10 Ctr Dr,Bldg 10,Room 11C207,MSC 1881, Bethesda, MD 20892 USA.
EM Ana.Olivera@nih.gov
FU Division of Intramural Research of NIAID within the National Institutes
of Health
FX Financial support was provided by the Division of Intramural Research of
NIAID within the National Institutes of Health.
NR 125
TC 13
Z9 14
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8561
EI 1557-8607
J9 IMMUNOL ALLERGY CLIN
JI Immunol. Allerg. Clin. North Am.
PD MAY
PY 2014
VL 34
IS 2
BP 219
EP +
DI 10.1016/j.iac.2014.01.002
PG 20
WC Allergy; Immunology
SC Allergy; Immunology
GA AH5RI
UT WOS:000336188300005
PM 24745671
ER
PT J
AU Richardson, BS
Anderson, WF
Barnholtz-Sloan, JS
Tucker, MA
Gerstenblith, MR
AF Richardson, Blakely S.
Anderson, William F.
Barnholtz-Sloan, Jill S.
Tucker, Margaret A.
Gerstenblith, Meg R.
TI The Age-Specific Effect Modification of Male Sex for Ulcerated Cutaneous
Melanoma
SO JAMA DERMATOLOGY
LA English
DT Article
ID AMERICAN JOINT COMMITTEE; CANCER STAGING SYSTEM; GENDER; EXPOSURE
AB IMPORTANCE Tumor ulceration is an important prognostic factor for cutaneous melanoma (CM). Previous studies demonstrated that the proportion of ulcerated to nonulcerated CM rose with increasing tumor depth. These frequency-based studies, however, were not adjusted for the population at risk.
OBJECTIVE To determine the absolute incidence of ulcerated CM by tumor depth, stratified by sex and age at diagnosis.
DESIGN, SETTING, AND PARTICIPANTS We compared ulcerated CM by tumor thicknesses (<= 1.00, 1.01-2.00, 2.01-4.00, and >= 4.01 mm), stratified by sex among younger (10-39 years) and older (40-84 years) non-Hispanic whites in the National Cancer Institute's Surveillance, Epidemiology, and End Results database from 2004 through 2008. Types of CM included superficial spreading, nodular, and unclassified in 5106 cases among 3206 men and 1900 women.
MAIN OUTCOMES AND MEASURES Incidence of ulcerated CM by tumor depth for younger and older men and women.
RESULTS The incidence of tumor ulceration was stable across all tumor depths among younger men and older women. Among younger women, it declined for the thickest lesions (0.08 per 100 000 for tumor depth >= 4.01 mm), although the trend was not statistically significant. In contrast, among older men, there was a statistically significant increase in ulceration for CM with a depth of approximately 1.4 per 100 000 for tumor depth of 2.00 mm or thicker.
CONCLUSIONS AND RELEVANCE Male sex is an age-specific effect modifier for ulcerated CM by tumor depth. Future studies and staging guidelines should consider the interaction among CM ulceration, thickness, sex, and age at diagnosis.
C1 [Richardson, Blakely S.; Gerstenblith, Meg R.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Dermatol, Sch Med, Cleveland, OH 44106 USA.
[Anderson, William F.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, Cleveland, OH 44106 USA.
[Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Gerstenblith, MR (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Dept Dermatol, Sch Med, 11100 Euclid Ave,Lakeside 3rd Floor Dermatol, Cleveland, OH 44106 USA.
EM meg.gerstenblith@uhhospitals.org
RI Tucker, Margaret/B-4297-2015
FU Char and Chuck Fowler Family Foundation; Dermatology Foundation Career
Development Award in Medical Dermatology; National Cancer Institute [P30
CA043703]
FX This study was supported by the Char and Chuck Fowler Family Foundation
and the Dermatology Foundation Career Development Award in Medical
Dermatology (Dr Gerstenblith), and in part by National Cancer Institute
grant P30 CA043703 from the Case Comprehensive Cancer Center (Dr
Barnholtz-Sloan). No other disclosures were reported.
NR 15
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6068
EI 2168-6084
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD MAY
PY 2014
VL 150
IS 5
BP 522
EP 525
DI 10.1001/jamadermatol.2013.7127
PG 4
WC Dermatology
SC Dermatology
GA AH2NH
UT WOS:000335957700009
PM 24599332
ER
PT J
AU Beal, MF
Oakes, D
Shoulson, I
Henchcliffe, C
Galpern, WR
Haas, R
Juncos, JL
Nutt, JG
Voss, TS
Ravina, B
Shults, CM
Helles, K
Snively, V
Lew, MF
Griebner, B
Watts, A
Gao, S
Pourcher, E
Bond, L
Kompoliti, K
Agarwal, P
Sia, C
Jog, M
Cole, L
Sultana, M
Kurlan, R
Richard, I
Deeley, C
Waters, CH
Figueroa, A
Arkun, A
Brodsky, M
Ondo, WG
Hunter, CB
Jimenez-Shahed, J
Palao, A
Miyasaki, JM
Julie, SO
Tetrud, J
Reys, L
Smith, K
Singer, C
Blenke, A
Russell, DS
Cotto, C
Friedman, JH
Lannon, M
Zhang, L
Drasby, E
Kumar, R
Subramanian, T
Ford, DS
Grimes, DA
Cote, D
Conway, J
Siderowf, AD
Evatt, ML
Sommerfeld, B
Lieberman, AN
Okun, MS
Rodriguez, RL
Merritt, S
Swartz, CL
Martin, WRW
King, P
Stover, N
Guthrie, S
Watts, RL
Ahmed, A
Fernandez, HH
Winters, A
Mari, Z
Dawson, TM
Dunlop, B
Feigin, AS
Shannon, B
Nirenberg, MJ
Ogg, M
Ellias, SA
Thomas, CA
Frei, K
Bodis-Wollner, I
Glazman, S
Mayer, T
Hauser, RA
Pahwa, R
Langhammer, A
Ranawaya, R
Derwent, L
Sethi, KD
Farrow, B
Prakash, R
Litvan, I
Robinson, A
Sahay, A
Gartner, M
Hinson, VK
Markind, S
Pelikan, M
Perlmutter, JS
Hartlein, J
Molho, E
Evans, S
Adler, CH
Duffy, A
Lind, M
Elmer, L
Davis, K
Spears, J
Wilson, S
Leehey, MA
Hermanowicz, N
Niswonger, S
Shill, HA
Obradov, S
Rajput, A
Cowper, M
Lessig, S
Song, D
Fontaine, D
Zadikoff, C
Williams, K
Blindauer, KA
Bergholte, J
Propsom, CS
Stacy, MA
Field, J
Mihaila, D
Chilton, M
Uc, EY
Sieren, J
Simon, DK
Kraics, L
Silver, A
Boyd, JT
Hamill, RW
Ingvoldstad, C
Young, J
Thomas, K
Kostyk, SK
Wojcieszek, J
Pfeiffer, RF
Panisset, M
Beland, M
Reich, SG
Cines, M
Zappala, N
Rivest, J
Zweig, R
Lumina, LP
Hilliard, CL
Grill, S
Kellermann, M
Tuite, P
Rolandelli, S
Kang, UJ
Young, J
Rao, J
Cook, MM
Severt, L
Boyar, K
AF Beal, M. Flint
Oakes, David
Shoulson, Ira
Henchcliffe, Claire
Galpern, Wendy R.
Haas, Richard
Juncos, Jorge L.
Nutt, John G.
Voss, Tiffini Smith
Ravina, Bernard
Shults, Clifford M.
Helles, Karen
Snively, Victoria
Lew, Mark F.
Griebner, Brian
Watts, Arthur
Gao, Shan
Pourcher, Emmanuelle
Bond, Louisette
Kompoliti, Katie
Agarwal, Pinky
Sia, Cherissa
Jog, Mandar
Cole, Linda
Sultana, Munira
Kurlan, Roger
Richard, Irene
Deeley, Cheryl
Waters, Cheryl H.
Figueroa, Angel
Arkun, Ani
Brodsky, Matthew
Ondo, William G.
Hunter, Christine B.
Jimenez-Shahed, Joohi
Palao, Alicia
Miyasaki, Janis M.
Julie, S. O.
Tetrud, James
Reys, Liza
Smith, Katharine
Singer, Carlos
Blenke, Anita
Russell, David S.
Cotto, Candace
Friedman, Joseph H.
Lannon, Margaret
Zhang, Lin
Drasby, Edward
Kumar, Rajeev
Subramanian, Thyagarajan
Ford, Donna Stuppy
Grimes, David A.
Cote, Diane
Conway, Jennifer
Siderowf, Andrew D.
Evatt, Marian Leslie
Sommerfeld, Barbara
Lieberman, Abraham N.
Okun, Michael S.
Rodriguez, Ramon L.
Merritt, Stacy
Swartz, Camille Louise
Martin, W. R. Wayne
King, Pamela
Stover, Natividad
Guthrie, Stephanie
Watts, Ray L.
Ahmed, Anwar
Fernandez, Hubert H.
Winters, Adrienna
Mari, Zoltan
Dawson, Ted M.
Dunlop, Becky
Feigin, Andrew S.
Shannon, Barbara
Nirenberg, Melissa Jill
Ogg, Mattson
Ellias, Samuel A.
Thomas, Cathi-Ann
Frei, Karen
Bodis-Wollner, Ivan
Glazman, Sofya
Mayer, Thomas
Hauser, Robert A.
Pahwa, Rajesh
Langhammer, April
Ranawaya, Ranjit
Derwent, Lorelei
Sethi, Kapil D.
Farrow, Buff
Prakash, Rajan
Litvan, Irene
Robinson, Annette
Sahay, Alok
Gartner, Maureen
Hinson, Vanessa K.
Markind, Samuel
Pelikan, Melisa
Perlmutter, Joel S.
Hartlein, Johanna
Molho, Eric
Evans, Sharon
Adler, Charles H.
Duffy, Amy
Lind, Marlene
Elmer, Lawrence
Davis, Kathy
Spears, Julia
Wilson, Stephanie
Leehey, Maureen A.
Hermanowicz, Neal
Niswonger, Shari
Shill, Holly A.
Obradov, Sanja
Rajput, Alex
Cowper, Marilyn
Lessig, Stephanie
Song, David
Fontaine, Deborah
Zadikoff, Cindy
Williams, Karen
Blindauer, Karen A.
Bergholte, Jo
Propsom, Clara Schindler
Stacy, Mark A.
Field, Joanne
Mihaila, Dragos
Chilton, Mark
Uc, Ergun Y.
Sieren, Jeri
Simon, David K.
Kraics, Lauren
Silver, Althea
Boyd, James T.
Hamill, Robert W.
Ingvoldstad, Christopher
Young, Jennifer
Thomas, Karen
Kostyk, Sandra K.
Wojcieszek, Joanne
Pfeiffer, Ronald F.
Panisset, Michel
Beland, Monica
Reich, Stephen G.
Cines, Michelle
Zappala, Nancy
Rivest, Jean
Zweig, Richard
Lumina, L. Pepper
Hilliard, Colette Lynn
Grill, Stephen
Kellermann, Marye
Tuite, Paul
Rolandelli, Susan
Kang, Un Jung
Young, Joan
Rao, Jayaraman
Cook, Maureen M.
Severt, Lawrence
Boyar, Karyn
TI A Randomized Clinical Trial of High-Dosage Coenzyme Q10 in Early
Parkinson Disease No Evidence of Benefit
SO JAMA NEUROLOGY
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; NEURODEGENERATIVE DISEASE;
HUNTINGTONS-DISEASE; DOUBLE-BLIND; VITAMIN-E; Q(10); MITOCHONDRIA;
THERAPY
AB IMPORTANCE Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit.
OBJECTIVE To examine whether CoQ10 could slow disease progression in early PD.
DESIGN, SETTING, AND PARTICIPANTS A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation.
INTERVENTIONS The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E.
MAIN OUTCOMES AND MEASURES Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo.
RESULTS The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P =.49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P =.21 relative to placebo).
CONCLUSIONS AND RELEVANCE Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit.
C1 [Beal, M. Flint; Henchcliffe, Claire; Arkun, Ani; Ogg, Mattson] New York Hosp, Weill Cornell Med Coll, Dept Neurol, New York, NY 10065 USA.
[Oakes, David; Helles, Karen; Snively, Victoria; Griebner, Brian; Watts, Arthur; Gao, Shan] Univ Rochester, Med Ctr, Dept Biostat, Rochester, NY 14642 USA.
[Shoulson, Ira] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Galpern, Wendy R.] Natl Inst Hlth, Bethesda, MD USA.
[Haas, Richard; Shults, Clifford M.; Litvan, Irene] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Juncos, Jorge L.; Evatt, Marian Leslie; Sommerfeld, Barbara] Emory Univ, Sch Med, Dept Neurol, WesleyWoods Ctr, Atlanta, GA 30322 USA.
[Nutt, John G.; Brodsky, Matthew] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Voss, Tiffini Smith] Merck, Rahway, NJ 07065 USA.
[Ravina, Bernard] Biogen Idec Inc, Cambridge, MA USA.
[Shults, Clifford M.] VA Med Ctr, San Diego, CA USA.
[Lew, Mark F.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA.
[Watts, Arthur; Richard, Irene; Deeley, Cheryl] Univ Rochester, Dept Neurol, Rochester, NY USA.
[Pourcher, Emmanuelle; Bond, Louisette] Quebec Memory & Motor Skills Disorders Res Ctr, Clin Sainte Anne, Quebec City, PQ, Canada.
[Kompoliti, Katie] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Agarwal, Pinky; Sia, Cherissa] Booth Gardner Parkinsons Care Ctr, Washington, DC USA.
[Jog, Mandar; Cole, Linda; Sultana, Munira] London Hlth Sci Ctr, London, ON, Canada.
[Kurlan, Roger] Overlook Med Ctr, Atlantic Neurosci Inst, Summit, NJ USA.
[Waters, Cheryl H.; Figueroa, Angel] Columbia Univ, Med Ctr, Neurol Inst, New York, NY USA.
[Ondo, William G.] Univ Texas Hlth Sci Ctr Houston, Dept Neurol, Houston, TX 77030 USA.
[Hunter, Christine B.; Jimenez-Shahed, Joohi; Palao, Alicia] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Miyasaki, Janis M.; Julie, S. O.] Univ Toronto, Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada.
[Tetrud, James; Reys, Liza; Smith, Katharine] Parkinsons Inst & Clin Ctr, Sunnyvale, CA USA.
[Singer, Carlos; Blenke, Anita] Univ Miami, Sch Med, Dept Neurol, Miami, FL USA.
[Russell, David S.; Cotto, Candace] Inst Neurodegenerat Disorders, New Haven, CT USA.
[Friedman, Joseph H.; Lannon, Margaret] Butler Hosp, Dept Neurol, Providence, RI 02906 USA.
[Friedman, Joseph H.] Butler Hosp, Alpert Med Sch, Providence, RI 02906 USA.
[Lannon, Margaret; Drasby, Edward] Port City Neurology Inc, Scarborough, ME USA.
[Zhang, Lin] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA.
[Zhang, Lin] Sacramento VA Med Ctr, Sacramento, CA USA.
[Subramanian, Thyagarajan; Ford, Donna Stuppy] Penn State Hershey Coll Med, Dept Neurol, Milton S Hershey Med Ctr, Hershey, PA USA.
[Grimes, David A.; Cote, Diane; Conway, Jennifer] Ottawa Civic Hosp, Ottawa, ON K1Y 4E9, Canada.
[Siderowf, Andrew D.] Avid Radiopharmaceut, Philadelphia, PA USA.
[Evatt, Marian Leslie] Atlanta VA Med Ctr, Atlanta, GA USA.
[Lieberman, Abraham N.] St Josephs Hosp, Barrow Neurol Inst, Muhammad Ali Parkinson Ctr, Phoenix, AZ USA.
[Okun, Michael S.; Rodriguez, Ramon L.; Merritt, Stacy; Swartz, Camille Louise] Univ Florida, Dept Neurol, Ctr Movement Disorders & Neurorestorat, Gainesville, FL USA.
[Martin, W. R. Wayne; King, Pamela] Univ Alberta, Glenrose Rehabil Hosp, Edmonton, AB, Canada.
[Stover, Natividad; Guthrie, Stephanie; Watts, Ray L.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA.
[Ahmed, Anwar; Fernandez, Hubert H.; Winters, Adrienna] Cleveland Clin, Dept Neurol, Ctr Neurol Restorat, Cleveland, OH 44106 USA.
[Mari, Zoltan; Dawson, Ted M.; Dunlop, Becky; Grill, Stephen] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Feigin, Andrew S.; Shannon, Barbara] Ctr Neurosci, Feinstein Inst Med Res, Manhasset, NY USA.
[Nirenberg, Melissa Jill] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA.
[Ellias, Samuel A.; Thomas, Cathi-Ann] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Frei, Karen] Parkinsons & Movement Disorder Inst, Fountain Valley, CA USA.
[Bodis-Wollner, Ivan; Glazman, Sofya; Mayer, Thomas] State Univ New York, Downstate Med Ctr, Brooklyn, NY USA.
[Hauser, Robert A.] Univ S Florida, Dept Neurol, Tampa, FL 33620 USA.
[Pahwa, Rajesh; Langhammer, April] Univ Kansas Med Ctr, Dept Neurol, Kansas City, KS USA.
[Ranawaya, Ranjit; Derwent, Lorelei] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada.
[Sethi, Kapil D.; Farrow, Buff; Prakash, Rajan] Georgia Hlth Sci Univ, Dept Neurol, Augusta, GA USA.
[Robinson, Annette] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA.
[Sahay, Alok; Gartner, Maureen] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Hinson, Vanessa K.] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA.
[Markind, Samuel; Pelikan, Melisa] Associated Neurol PC, Danbury, CT USA.
[Perlmutter, Joel S.; Hartlein, Johanna] Washington Univ, Dept Neurol, St Louis, MO USA.
[Molho, Eric; Evans, Sharon] Albany Med Ctr, Movement Disorders Ctr, Albany, NY USA.
[Adler, Charles H.; Duffy, Amy; Lind, Marlene] Mayo Clin, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, Scottsdale, AZ USA.
[Elmer, Lawrence] Univ Toledo, Ctr Neurol Hlth, Toledo, OH 43606 USA.
[Davis, Kathy; Spears, Julia; Wilson, Stephanie] Med Univ Ohio Toledo, Dept Neurol, Toledo, OH USA.
[Leehey, Maureen A.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA.
[Hermanowicz, Neal; Niswonger, Shari] Univ Calif Irvine, Dept Neurol, Irvine Med Ctr, Irvine, CA 92717 USA.
[Shill, Holly A.; Obradov, Sanja] Banner Sun Hlth Res Inst, Sun City, AZ USA.
[Rajput, Alex; Cowper, Marilyn] Univ Saskatchewan, Royal Univ Hosp, Dept Neurol, Saskatoon, SK S7N 0W0, Canada.
[Lessig, Stephanie; Song, David; Fontaine, Deborah] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA.
[Zadikoff, Cindy; Williams, Karen] Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Blindauer, Karen A.; Bergholte, Jo; Propsom, Clara Schindler] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Stacy, Mark A.; Field, Joanne] Duke Univ, Dept Neurol, Durham, NC USA.
[Mihaila, Dragos; Chilton, Mark] State Univ New York Upstate Med Ctr, Syracuse, NY USA.
[Mihaila, Dragos; Chilton, Mark] Syracuse VA Med Ctr, Syracuse, NY USA.
[Uc, Ergun Y.; Sieren, Jeri] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA.
[Simon, David K.; Kraics, Lauren; Silver, Althea] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Simon, David K.; Kraics, Lauren; Silver, Althea] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Boyd, James T.; Hamill, Robert W.; Ingvoldstad, Christopher; Young, Jennifer] Univ Vermont, Coll Med, Dept Neurol, Burlington, VT 05405 USA.
[Thomas, Karen; Kostyk, Sandra K.] Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA.
[Wojcieszek, Joanne] Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA.
[Pfeiffer, Ronald F.] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
[Panisset, Michel; Beland, Monica] CHUM Hop Notre Dame, Dept Neurol, Montreal, PQ, Canada.
[Reich, Stephen G.; Cines, Michelle; Zappala, Nancy] Univ Maryland, Maryland Sch Sci, Dept Neurol, Baltimore, MD 21201 USA.
[Rivest, Jean] Univ Sherbrooke, Dept Neurol, Sherbrooke, PQ J1K 2R1, Canada.
[Zweig, Richard; Lumina, L. Pepper] Louisiana State Univ, Hlth Sci Ctr, Dept Neurol, Shreveport, LA 71105 USA.
[Hilliard, Colette Lynn] Lewis Hall Singletary Oncol Ctr, Thomasville, GA USA.
[Kellermann, Marye] Parkinson & Movement Disorders Ctr Maryland, Elkridge, MD USA.
[Tuite, Paul; Rolandelli, Susan] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA.
[Kang, Un Jung; Young, Joan] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA.
[Rao, Jayaraman; Cook, Maureen M.] Ochsner Clin Fdn, Dept Neurol, New Orleans, LA USA.
[Severt, Lawrence; Boyar, Karyn] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA.
RP Beal, MF (reprint author), New York Hosp, Weill Cornell Med Coll, Dept Neurol, 525 E 68th St, New York, NY 10065 USA.
EM fbeal@med.cornell.edu
OI Miyasaki, Janis/0000-0002-6372-6007
FU National Institute of Neurological Disorders and Stroke to the Cornell
University [U01 NS 050324]; [U01 NS050573]
FX The study was funded by grants from the National Institute of
Neurological Disorders and Stroke to the Cornell University (U01 NS
050324; Dr Beal, PI) and to the University of Rochester (U01 NS050573;
Dr Oakes, PI). We were also supported by the Parkinson's Disease
Foundation with regard to facilitating minority enrollment.
NR 28
TC 59
Z9 59
U1 4
U2 21
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD MAY
PY 2014
VL 71
IS 5
BP 543
EP 552
DI 10.1001/jamaneurol.2014.131
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH2MX
UT WOS:000335956700005
ER
PT J
AU Frohman, EM
Monaco, MC
Remington, G
Ryschkewitsch, C
Jensen, PN
Johnson, K
Perkins, M
Liebner, J
Greenberg, B
Monson, N
Frohman, TC
Douek, D
Major, EO
AF Frohman, Elliot M.
Monaco, Maria Chiara
Remington, Gina
Ryschkewitsch, Caroline
Jensen, Peter N.
Johnson, Kory
Perkins, Molly
Liebner, Julia
Greenberg, Benjamin
Monson, Nancy
Frohman, Teresa C.
Douek, Daniel
Major, Eugene O.
TI JC Virus in CD34(+) and CD19(+) Cells in Patients With Multiple
Sclerosis Treated With Natalizumab
SO JAMA NEUROLOGY
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HEMATOPOIETIC PROGENITOR
CELLS; TONSILLAR STROMAL CELLS; HUMAN CYTOMEGALOVIRUS; ANTIBODY
NATALIZUMAB; RISK STRATIFICATION; VIRAL LATENCY; B-LYMPHOCYTES;
BONE-MARROW; GLIAL-CELLS
AB IMPORTANCE Infection with JC virus (JCV) may lead to development of demyelinating progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS) who are treated with natalizumab.
OBJECTIVE To determine whether mononuclear cells in circulation from MS patients treated with natalizumab harbor JCV DNA.
DESIGN, SETTING, AND PARTICIPANTS In this prospective investigation, we enrolled 49 MS patients from the Clinical Center for Multiple Sclerosis at The University of Texas Southwestern Medical Center and 18 healthy volunteers. We drew 120-mL blood samples from 26 MS patients at baseline and at approximately 3-month intervals to 10 months during the course of natalizumab infusions. One blood sample was drawn from 23 MS patients receiving natalizumab for more than 24 months and from 18 healthy volunteers.
INTERVENTIONS Natalizumab treatment of MS.
MAIN OUTCOMES AND MEASURES The blood sampleswere separated using flow cytometry into CD34(+), CD19(+), and CD3(+) cell subsets; DNA templates were prepared using quantitative polymerase chain reaction for JCV DNA identification. Plasma samples were tested for anti-JCV antibodies by enzyme-linked A1AQ immunosorbent assays performed at the Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological and Communicative Diseases and Stroke.
RESULTS Thirteen of the 26 patients (50%) with baseline and follow-up blood samples had detectable viral DNA in at least 1 cell compartment at 1 or more points. Ten of the 23 patients (44%) receiving treatment for more than 24 months and 3 of the 18 healthy volunteers (17%) also had detectable viral DNA in 1 or more cell compartment. Fifteen of the 49 MS patients (31%) were confirmed to harbor JCV in CD34(+) cells and 12 of 49 (24%) in CD19(+) cells. Only 1 of 18 healthy volunteers were viremic in CD34(+) cells and none in CD19(+) cells. Nine patients and 1 healthy volunteer were viremic but had seronegative test results for JCV antibodies.
CONCLUSIONS AND RELEVANCE JC virus DNA was detectable within cell compartments of natalizumab-treated MS patients after treatment inception and longer. JC virus DNA may harbor in CD34(+) cells in bone marrow that mobilize into the peripheral circulation at high concentrations. Latently infected cells initiate differentiation to CD19(+) cells that favors growth of JCV. These data link the mechanism of natalizumab treatment with progressive multifocal leukoencephalopathy.
C1 [Frohman, Elliot M.; Remington, Gina; Greenberg, Benjamin; Monson, Nancy; Frohman, Teresa C.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA.
[Frohman, Elliot M.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA.
[Monaco, Maria Chiara; Remington, Gina; Jensen, Peter N.; Major, Eugene O.] NIH, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA.
[Johnson, Kory] Natl Inst Neurol & Communicat Dis & Stroke, Bioinformat Sect, NIH, Bethesda, MD USA.
[Perkins, Molly; Liebner, Julia; Douek, Daniel] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Frohman, EM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Neurol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM elliot.frohman@utsouthwestern.edu; majorg@ninds.nih.gov
FU Division of Intramural Research; National Institute of Neurological and
Communicative Diseases [NINDS]; National Institute of Allergy and
Infectious Disease [NIAID]; National Multiple Sclerosis Society [RG
3780A3/3]
FX This study was supported by Division of Intramural Research funds
(National Institute of Neurological and Communicative Diseases [NINDS]
and National Institute of Allergy and Infectious Disease [NIAID]
laboratories), by contract HHSN 271200900268P (LMMN, The University of
Texas Southwestern Medical Center LMMN, and NINDS), and by grant RG
3780A3/3 from the National Multiple Sclerosis Society (Dr Frohman).
NR 35
TC 37
Z9 37
U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD MAY
PY 2014
VL 71
IS 5
BP 596
EP 602
DI 10.1001/jamaneurol.2014.63
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH2MX
UT WOS:000335956700012
PM 24664166
ER
PT J
AU Spira, AP
An, Y
Resnick, SM
AF Spira, Adam P.
An, Yang
Resnick, Susan M.
TI Self-Reported Sleep and beta-Amyloid Deposition in Older Adults Reply
SO JAMA NEUROLOGY
LA English
DT Letter
C1 [Spira, Adam P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.
[An, Yang; Resnick, Susan M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Spira, AP (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, 624 N Broadway,Hampton House,Room 794, Baltimore, MD 21205 USA.
EM aspira@jhsph.edu
FU Intramural NIH HHS; NIA NIH HHS [1K01AG033195, K01 AG033195]
NR 1
TC 1
Z9 1
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD MAY
PY 2014
VL 71
IS 5
BP 651
EP 652
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH2MX
UT WOS:000335956700024
PM 24818679
ER
PT J
AU McNeil, E
Gunas, H
Koroshetz, W
AF McNeil, Elizabeth
Gunas, Heather
Koroshetz, Walter
TI The Future of Neuroscience Clinical Trials
SO JAMA NEUROLOGY
LA English
DT Letter
C1 [McNeil, Elizabeth; Koroshetz, Walter] NINDS, NIH, Bethesda, MD 20892 USA.
[Gunas, Heather] NCI, NIH, Bethesda, MD 20892 USA.
RP McNeil, E (reprint author), NINDS, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM mcneilde@ninds.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD MAY
PY 2014
VL 71
IS 5
BP 652
EP 652
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH2MX
UT WOS:000335956700025
PM 24818680
ER
PT J
AU Schoenbaum, M
Kessler, RC
Gilman, SE
Colpe, LJ
Heeringa, SG
Stein, MB
Ursano, RJ
Cox, KL
AF Schoenbaum, Michael
Kessler, Ronald C.
Gilman, Stephen E.
Colpe, Lisa J.
Heeringa, Steven G.
Stein, Murray B.
Ursano, Robert J.
Cox, Kenneth L.
CA Army STARRS Collaborators
TI Predictors of Suicide and Accident Death in the Army Study to Assess
Risk and Resilience in Servicemembers (Army STARRS) Results From the
Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)
SO JAMA PSYCHIATRY
LA English
DT Article
ID US MILITARY; PSYCHOPATHOLOGY; ATTRITION; PERSONNEL; SOLDIERS
AB IMPORTANCE The Army Study to Assess Risk and Resilience in Servicemembers ( Army STARRS) is a multicomponent study designed to generate actionable recommendations to reduce Army suicides and increase knowledge of risk and resilience factors for suicidality.
OBJECTIVES To present data on prevalence, trends, and basic sociodemographic and Army experience correlates of suicides and accident deaths among active duty Regular Army soldiers between January 1, 2004, and December 31, 2009, and thereby establish a foundation for future Army STARRS investigations.
DESIGN, SETTING, AND PARTICIPANTS Analysis of trends and predictors of suicide and accident deaths using Army and Department of Defense administrative data systems. Participants were all members of the US Regular Army serving at any time between 2004 and 2009.
MAIN OUTCOMES AND MEASURES Death by suicide or accident during active Army service.
RESULTS The suicide rate rose between 2004 and 2009 among never deployed and currently and previously deployed Regular Army soldiers. The accident death rate fell sharply among currently deployed soldiers, remained constant among the previously deployed, and trended upward among the never deployed. Increased suicide risk was associated with being a man (or a woman during deployment), white race/ethnicity, junior enlisted rank, recent demotion, and current or previous deployment. Sociodemographic and Army experience predictors were generally similar for suicides and accident deaths. Time trends in these predictors and in the Army's increased use of accession waivers (which relaxed some qualifications for new soldiers) do not explain the rise in Army suicides.
CONCLUSIONS AND RELEVANCE Predictors of Army suicides were largely similar to those reported elsewhere for civilians, although some predictors distinct to Army service emerged that deserve more in-depth analysis. The existence of a time trend in suicide risk among never-deployed soldiers argues indirectly against the view that exposure to combat-related trauma is the exclusive cause of the increase in Army suicides.
C1 [Schoenbaum, Michael; Colpe, Lisa J.] NIMH, Bethesda, MD 20892 USA.
[Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Psychiat & Family, La Jolla, CA 92093 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Prevent Med, La Jolla, CA 92093 USA.
[Stein, Murray B.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Sch Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD USA.
[Cox, Kenneth L.] US Army Publ Hlth Command, Aberdeen Proving Ground, MD USA.
RP Schoenbaum, M (reprint author), NIMH, 6001 Execut Blvd,Room 6226,Mail Stop Code 9669, Bethesda, MD 20892 USA.
EM schoenbaumm@mail.nih.gov
RI Gilman, Stephen/E-7632-2010
OI Gilman, Stephen/0000-0002-8331-6419
FU Department of the Army; National Institute of Mental Health, National
Institutes of Health, US Department of Health and Human Service
[UO1MHO87981]
FX The Army STARRS was sponsored by the Department of the Army and funded
under cooperative agreement UO1MHO87981 with the National Institute of
Mental Health, National Institutes of Health, US Department of Health
and Human Services.
NR 18
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U1 1
U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2014
VL 71
IS 5
BP 493
EP 503
DI 10.1001/jamapsychiatry.2013.4417
PG 11
WC Psychiatry
SC Psychiatry
GA AH2JP
UT WOS:000335947600006
PM 24590048
ER
PT J
AU Kessler, RC
Heeringa, SG
Stein, MB
Colpe, LJ
Fullerton, CS
Hwang, I
Naifeh, JA
Nock, MK
Petukhova, M
Sampson, NA
Schoenbaum, M
Zaslavsky, AM
Ursano, RJ
AF Kessler, Ronald C.
Heeringa, Steven G.
Stein, Murray B.
Colpe, Lisa J.
Fullerton, Carol S.
Hwang, Irving
Naifeh, James A.
Nock, Matthew K.
Petukhova, Maria
Sampson, Nancy A.
Schoenbaum, Michael
Zaslavsky, Alan M.
Ursano, Robert J.
CA Army STARRS Collaborators
TI Thirty-Day Prevalence of DSM-IV Mental Disorders Among Nondeployed
Soldiers in the US Army Results From the Army Study to Assess Risk and
Resilience in Servicemembers (Army STARRS)
SO JAMA PSYCHIATRY
LA English
DT Article
ID COMORBIDITY SURVEY REPLICATION; SUBSTANCE USE DISORDERS; AGE-OF-ONSET;
POSTTRAUMATIC-STRESS; MILITARY PERSONNEL; COMBAT EXPOSURE; HEALTH
OUTCOMES; SEX-DIFFERENCES; MARITAL-STATUS; GULF-WAR
AB IMPORTANCE Although high rates of current mental disorder are known to exist in the US Army, little is known about the proportions of these disorders that had onsets prior to enlistment.
OBJECTIVE To estimate the proportions of 30-day DSM-IV mental disorders among nondeployed US Army personnel with first onsets prior to enlistment and the extent which role impairments associated with 30-day disorders differ depending on whether the disorders had pre-vs post-enlistment onsets.
DESIGN, SETTING, AND PARTICIPANTS A representative sample of 5428 soldiers participating in the Army Study to Assess Risk and Resilience in Servicemembers completed self-administered questionnaires and consented to linkage of questionnaire responses with administrative records.
MAIN OUTCOMES AND MEASURES Thirty-day DSM-IV internalizing (major depressive, bipolar, generalized anxiety, panic, and posttraumatic stress) and externalizing (attention-deficit/ hyperactivity, intermittent explosive, alcohol/drug) disorders were assessed with validated self-report scales. Age at onset was assessed retrospectively. Role impairment was assessed with a modified Sheehan Disability Scale.
RESULTS A total of 25.1% of respondents met criteria for any 30-day disorder (15.0% internalizing; 18.4% externalizing) and 11.1% for multiple disorders. A total of 76.6% of cases reported pre-enlistment age at onset of at least one 30-day disorder (49.6% internalizing; 81.7% externalizing). Also, 12.8% of respondents reported severe role impairment. Controlling for sociodemographic and Army career correlates, which were broadly consistent with other studies, 30-day disorders with pre-enlistment (chi(2)(8) = 131.8, P <.001) and post-enlistment (chi(2)(7) 7 = 123.8, P <.001) ages at onset both significantly predicted severe role impairment, although pre-enlistment disorders were more consistent powerful predictors (7 of 8 disorders significant; odds ratios, 1.6-11.4) than post-enlistment disorders (5 of 7 disorders significant; odds ratios, 1.5-7.7). Population-attributable risk proportions of severe role impairment were 21.7% for pre-enlistment disorders, 24.3% for post-enlistment disorders, and 43.4% for all disorders.
CONCLUSIONS AND RELEVANCE Interventions to limit accession or increase resilience of new soldiers with pre-enlistment mental disorders might reduce prevalence and impairments of mental disorders in the US Army.
C1 [Kessler, Ronald C.; Hwang, Irving; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
[Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Fullerton, Carol S.; Naifeh, James A.; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM ncs@hcp.med.harvard.edu
FU Department of the Army; US Department of Health and Human Services,
National Institutes of Health, National Institute of Mental Health
[UO1MHO87981]
FX Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement UO1MHO87981 with the US Department of Health and
Human Services, National Institutes of Health, National Institute of
Mental Health.
NR 78
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U1 1
U2 25
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2014
VL 71
IS 5
BP 504
EP 513
DI 10.1001/jamapsychiatry.2014.28
PG 10
WC Psychiatry
SC Psychiatry
GA AH2JP
UT WOS:000335947600007
PM 24590120
ER
PT J
AU Nock, MK
Stein, MB
Heeringa, SG
Ursano, RJ
Colpe, LJ
Fullerton, CS
Hwang, I
Naifeh, JA
Sampson, NA
Schoenbaum, M
Zaslavsky, AM
Kessler, RC
AF Nock, Matthew K.
Stein, Murray B.
Heeringa, Steven G.
Ursano, Robert J.
Colpe, Lisa J.
Fullerton, Carol S.
Hwang, Irving
Naifeh, James A.
Sampson, Nancy A.
Schoenbaum, Michael
Zaslavsky, Alan M.
Kessler, Ronald C.
CA Army STARRS Collaborators
TI Prevalence and Correlates of Suicidal Behavior Among Soldiers Results
From the Army Study to Assess Risk and Resilience in Servicemembers
(Army STARRS)
SO JAMA PSYCHIATRY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; MILITARY; VETERANS; ASSOCIATIONS;
ADOLESCENTS; HISTORY; TRAUMA; ADULTS
AB IMPORTANCE The suicide rate among US Army soldiers has increased substantially in recent years.
OBJECTIVES To estimate the lifetime prevalence and sociodemographic, Army career, and psychiatric predictors of suicidal behaviors among nondeployed US Army soldiers.
DESIGN, SETTING, AND PARTICIPANTS A representative cross-sectional survey of 5428 nondeployed soldiers participating in a group self-administered survey.
MAIN OUTCOMES AND MEASURES Lifetime suicidal ideation, suicide plans, and suicide attempts.
RESULTS The lifetime prevalence estimates of suicidal ideation, suicide plans, and suicide attempts are 13.9%, 5.3%, and 2.4%. Most reported cases (47.0%-58.2%) had pre-enlistment onsets. Pre-enlistment onset rates were lower than in a prior national civilian survey (with imputed/ simulated age at enlistment), whereas post-enlistment onsets of ideation and plans were higher, and post-enlistment first attempts were equivalent to civilian rates. Most reported onsets of plans and attempts among ideators (58.3%-63.3%) occur within the year of onset of ideation. Post-enlistment attempts are positively related to being a woman (with an odds ratio [OR] of 3.3 [95% CI, 1.5-7.5]), lower rank (OR = 5.8 [95% CI, 1.8-18.1]), and previously deployed (OR = 2.4-3.7) and are negatively related to being unmarried (OR = 0.1-0.8) and assigned to Special Operations Command (OR = 0.0 [95% CI, 0.0-0.0]). Five mental disorders predict post-enlistment first suicide attempts in multivariate analysis: pre-enlistment panic disorder (OR = 0.1 [95% CI, 0.0-0.8]), pre-enlistment posttraumatic stress disorder (OR = 0.1 [95% CI, 0.0-0.7]), post-enlistment depression (OR = 3.8 [95% CI, 1.2-11.6]), and both pre-and post-enlistment intermittent explosive disorder (OR = 3.7-3.8). Four of these 5 ORs (posttraumatic stress disorder is the exception) predict ideation, whereas only post-enlistment intermittent explosive disorder predicts attempts among ideators. The population-attributable risk proportions of lifetime mental disorders predicting post-enlistment suicide attempts are 31.3% for pre-enlistment onset disorders, 41.2% for post-enlistment onset disorders, and 59.9% for all disorders.
CONCLUSIONS AND RELEVANCE The fact that approximately one-third of post-enlistment suicide attempts are associated with pre-enlistment mental disorders suggests that pre-enlistment mental disorders might be targets for early screening and intervention. The possibility of higher fatality rates among Army suicide attempts than among civilian suicide attempts highlights the potential importance of means control (ie, restricting access to lethal means [such as firearms]) as a suicide prevention strategy.
C1 [Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Ursano, Robert J.; Fullerton, Carol S.; Naifeh, James A.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
[Hwang, Irving; Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Nock, MK (reprint author), Harvard Univ, Dept Psychol, William James Hall,1280,33 Kirkland St, Cambridge, MA 02138 USA.
EM nock@wjh.harvard.edu
FU Department of the Army; US Department of Health and Human Services,
National Institutes of Health, National Institute of Mental Health
(NIMH) [UO1MHO87981]
FX Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement UO1MHO87981 with the US Department of Health and
Human Services, National Institutes of Health, National Institute of
Mental Health (NIMH).
NR 42
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U1 7
U2 24
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2014
VL 71
IS 5
BP 514
EP 522
DI 10.1001/jamapsychiatry.2014.30
PG 9
WC Psychiatry
SC Psychiatry
GA AH2JP
UT WOS:000335947600008
PM 24590178
ER
PT J
AU Lerman, C
Gu, H
Loughead, J
Ruparel, K
Yang, YH
Stein, EA
AF Lerman, Caryn
Gu, Hong
Loughead, James
Ruparel, Kosha
Yang, Yihong
Stein, Elliot A.
TI Large-Scale Brain Network Coupling Predicts Acute Nicotine Abstinence
Effects on Craving and Cognitive Function
SO JAMA PSYCHIATRY
LA English
DT Article
ID INDEPENDENT COMPONENT ANALYSIS; RESTING-STATE NETWORKS; DEFAULT-MODE;
WORKING-MEMORY; CONNECTIVITY MRI; HEAD MOTION; ATTENTION; TASK;
VARENICLINE; VALIDATION
AB IMPORTANCE Interactions of large-scale brain networks may underlie cognitive dysfunctions in psychiatric and addictive disorders.
OBJECTIVES To test the hypothesis that the strength of coupling among 3 large-scale brain networks-salience, executive control, and default mode-will reflect the state of nicotine withdrawal (vs smoking satiety) and will predict abstinence-induced craving and cognitive deficits and to develop a resource allocation index (RAI) that reflects the combined strength of interactions among the 3 large-scale networks.
DESIGN, SETTING, AND PARTICIPANTS A within-subject functional magnetic resonance imaging study in an academic medical center compared resting-state functional connectivity coherence strength after 24 hours of abstinence and after smoking satiety. We examined the relationship of abstinence-induced changes in the RAI with alterations in subjective, behavioral, and neural functions. We included 37 healthy smoking volunteers, aged 19 to 61 years, for analyses.
INTERVENTIONS Twenty-four hours of abstinence vs smoking satiety.
MAIN OUTCOMES AND MEASURES Inter-network connectivity strength (primary) and the relationship with subjective, behavioral, and neural measures of nicotine withdrawal during abstinence vs smoking satiety states (secondary).
RESULTS The RAI was significantly lower in the abstinent compared with the smoking satiety states (left RAI, P =.002; right RAI, P =.04), suggesting weaker inhibition between the default mode and salience networks. Weaker inter-network connectivity (reduced RAI) predicted abstinence-induced cravings to smoke (r = -0.59; P =.007) and less suppression of default mode activity during performance of a subsequent working memory task (ventromedial prefrontal cortex, r = -0.66, P =.003; posterior cingulate cortex, r = -0.65, P =.001).
CONCLUSIONS AND RELEVANCE Alterations in coupling of the salience and default mode networks and the inability to disengage from the default mode network may be critical in cognitive/affective alterations that underlie nicotine dependence.
C1 [Lerman, Caryn; Loughead, James] Univ Penn, Dept Psychiat, Ctr Interdisciplinary Res Nicotine Addict, Philadelphia, PA 19104 USA.
[Gu, Hong; Yang, Yihong; Stein, Elliot A.] NIDA, Intramural Res Program, Baltimore, MD USA.
[Ruparel, Kosha] Univ Penn, Dept Psychiat, Brain Behav Lab, Philadelphia, PA 19104 USA.
RP Lerman, C (reprint author), Univ Penn, Dept Psychiat, Ctr Interdisciplinary Res Nicotine Addict, 3535 Market St,Ste 4100, Philadelphia, PA 19104 USA.
EM clerman@upenn.edu
FU Intramural Research Program of the National Institute [P50 CA143187, R03
DA027438]; Commonwealth of Pennsylvania Department of Health
FX This study was supported by grants P50 CA143187 and R03 DA027438 (Dr
Lerman), the Intramural Research Program of the National Institute on
Drug Abuse (Dr Stein), and the Commonwealth of Pennsylvania Department
of Health.
NR 51
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U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD MAY
PY 2014
VL 71
IS 5
BP 523
EP 530
DI 10.1001/jamapsychiatry.2013.4091
PG 8
WC Psychiatry
SC Psychiatry
GA AH2JP
UT WOS:000335947600009
PM 24622915
ER
PT J
AU Pradhan, I
Zeldin, DC
Ledent, C
Mustafa, JS
Falck, JR
Nayeem, MA
AF Pradhan, Isha
Zeldin, Darryl C.
Ledent, Catherine
Mustafa, Jamal S.
Falck, John R.
Nayeem, Mohammed A.
TI High Salt Diet Exacerbates Vascular Contraction in the Absence of
Adenosine A(2A) Receptor
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
LA English
DT Article
DE A1AR; HS; relaxation; contraction; cyp4a; NS; cyp2c29; A2AAR
ID RAT PREGLOMERULAR MICROVESSELS; EPOXYEICOSATRIENOIC ACIDS;
ARACHIDONIC-ACID; TUBULOGLOMERULAR FEEDBACK; AFFERENT ARTERIOLES; AORTIC
RELAXATION; CYP EPOXYGENASES; SENSITIVE RATS; BLOOD-PRESSURE;
NITRIC-OXIDE
AB High salt (4% NaCl, HS) diet modulates adenosine-induced vascular response through adenosine A(2A) receptor (A(2A)AR). Evidence suggests that A(2A)AR stimulates cyp450-epoxygenases, leading to epoxyeicosatrienoic acids (EETs) generation. The aim of this study was to understand the vascular reactivity to HS and underlying signaling mechanism in the presence or absence of A(2A)AR. Therefore, we hypothesized that HS enhances adenosine-induced relaxation through EETs in A(2A)AR(+/+), but exaggerates contraction in A(2A)AR(-/-). Organ bath and Western blot experiments were conducted in HS and normal salt (NS, 0.18% NaCl)-fed A(2A)AR(+/+) and A(2A)AR(-/-) mice aorta. HS produced concentration-dependent relaxation to non-selective adenosine analog, NECA in A(2A)AR(+/+), whereas contraction was observed in A(2A)AR(-/-) mice and this was attenuated by A(1)AR antagonist (DPCPX). CGS 21680 (selective A(2A)AR agonist) enhanced relaxation in HS-A(2A)AR(+/+) versus NS-A(2A)AR(+/+), which was blocked by EETs antagonist (14,15-EEZE). Compared with NS, HS significantly upregulated the expression of vasodilators A(2A)AR and cyp2c29, whereas vasoconstrictors A(1)AR and cyp4a in A(2A)AR(+/+) were downregulated. In A(2A)AR(-/-) mice, however, HS significantly downregulated the expression of cyp2c29, whereas A(1)AR and cyp4a were upregulated compared with A(2A)AR(+/+) mice. Hence, our data suggest that in A(2A)AR(+/+), HS enhances A(2A)AR-induced relaxation through increased cyp-expoxygenases-derived EETs and decreased A(1)AR levels, whereas in A(2A)AR(-/-), HS exaggerates contraction through decreased cyp-epoxygenases and increased A(1)AR levels.
C1 [Pradhan, Isha; Mustafa, Jamal S.; Nayeem, Mohammed A.] W Virginia Univ, Sch Pharm, Ctr Cardiovasc & Resp Sci,Sch Med, Dept Physiol & Pharmacol,Dept Basic Pharmaceut Sc, Morgantown, WV 26506 USA.
[Zeldin, Darryl C.] NIEHS, Div Intramural Res, Dept Pulm, NIH, Res Triangle Pk, NC 27709 USA.
[Ledent, Catherine] Univ Libre Bruxelles, IRIBHN, Brussels, Belgium.
[Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA.
RP Nayeem, MA (reprint author), W Virginia Univ, Sch Pharm, Ctr Cardiovasc & Resp Sci,Sch Med, Dept Physiol & Pharmacol,Dept Basic Pharmaceut Sc, Biomed Res Bldg,2nd Floor,Room 220, Morgantown, WV 26506 USA.
EM mnayeem@hsc.wvu.edu
RI Nayeem, Mohammed/A-3949-2017
OI Nayeem, Mohammed/0000-0002-7827-4760
FU WVU; National Institutes of Health [HL-114559, HL-094447, HL 027339, GM-
31278, z01-ES025034]
FX Supported by Bridge Grant funding (WVU), startup funding (WVU) and
National Institutes of Health HL-114559 to M. A. Nayeem; HL-094447 and
HL 027339 to S. J. Mustafa; GM- 31278 to J. R. Falck; and z01-ES025034
to D. C. Zeldin.
NR 39
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0160-2446
EI 1533-4023
J9 J CARDIOVASC PHARM
JI J. Cardiovasc. Pharmacol.
PD MAY
PY 2014
VL 63
IS 5
BP 385
EP 394
DI 10.1097/FJC.0000000000000058
PG 10
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA AH2KZ
UT WOS:000335951500001
PM 24390173
ER
PT J
AU Haverkamp, MH
Marciano, BE
Frucht, DM
Jain, A
van de Vosse, E
Holland, SM
AF Haverkamp, Margje H.
Marciano, Beatriz E.
Frucht, David M.
Jain, Ashish
van de Vosse, Esther
Holland, Steven M.
TI Correlating Interleukin-12 Stimulated Interferon-gamma Production and
the Absence of Ectodermal Dysplasia and Anhidrosis (EDA) in Patients
with Mutations in NF-kappa B Essential Modulator (NEMO)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE NF-kappa B essential modulator (NEMO); ectodermal; dysplasia and
anhidrosis (EDA); nontuberculous; mycobacteria (NTM); cytokines
ID AVIUM COMPLEX INFECTION; IMMUNE-DEFICIENCY; INCONTINENTIA PIGMENTI;
IMMUNODEFICIENCY; RECEPTOR; UBIQUITINATION; COSTIMULATION; SYSTEM;
CELLS; CHILD
AB Objective Patients with hypomorphic mutations in Nuclear Factor-kappa B Essential Modulator (NEMO) are immunodeficient (ID) and most display ectodermal dysplasia and anhidrosis (EDA). We compared cytokine production by NEMO-ID patients with and without EDA.
Methods PBMCs of NEMO-ID patients, four with EDA carrying E315A, C417R, D311N and Q403X, and three without EDA carrying E315A, E311_L333del and R254G, were cultured with PHA, PHA plus IL-12p70, LPS, LPS plus IFN-gamma, TNF and IL-1 beta. The production of various cytokines was measured in the supernatants. Fifty-nine healthy individuals served as controls.
Results PBMCs of NEMO-ID patients without EDA produce subnormal amounts of IFN-gamma after stimulation with PHA, but normal amounts of IFN-gamma after PHA plus IL-12p70. In contrast, IFN-gamma production by patients with EDA was low in both cases. Patients with EDA also generate lower PHA-stimulated IL-10 and IL-1 beta than controls, whereas the production of these cytokines by patients without EDA was normal.
Conclusion Responses of PBMCs in NEMO-ID patients with EDA to PHA with and without IL-12p70 appear less robust than in NEMO-ID patients without EDA. This possibly indicates a better preserved NEMO function in our patients without EDA.
C1 [Haverkamp, Margje H.; van de Vosse, Esther] Leiden Univ, Med Ctr, Dept Infect Dis, NL-2333 ZA Leiden, Netherlands.
[Haverkamp, Margje H.; Marciano, Beatriz E.; Holland, Steven M.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Frucht, David M.] US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA.
[Jain, Ashish] NIH, Lab Host Defenses, Bethesda, MD 20892 USA.
RP Haverkamp, MH (reprint author), Leiden Univ, Med Ctr, Dept Infect Dis, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands.
EM m.h.haverkamp@lumc.nl
RI van de Vosse, Esther/B-7285-2009
OI van de Vosse, Esther/0000-0001-5199-3426
FU Fulbright/Netherland America Foundation, the intramural Research Program
of the NIH; National Institute of Allergy and Infectious Diseases;
Netherlands Organisation for Scientific Research (NWO); Stichting
Fundatie Vrijvrouwe van Renswoude and the Stichting Algemeen Studiefonds
FX M.H. has been supported by grants from the Fulbright/Netherland America
Foundation, the intramural Research Program of the NIH, National
Institute of Allergy and Infectious Diseases, the Netherlands
Organisation for Scientific Research (NWO), the Stichting Doctor
Catharine van Tussenbroek Fonds, the Prins Bernhard Cultuurfonds, the
Leids Universiteits Fonds, the Stichting Dr Hendrik Muller's
Vaderlandsch Fonds, the Stichting Fundatie Vrijvrouwe van Renswoude and
the Stichting Algemeen Studiefonds.
NR 29
TC 3
Z9 4
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD MAY
PY 2014
VL 34
IS 4
BP 436
EP 443
DI 10.1007/s10875-014-9998-2
PG 8
WC Immunology
SC Immunology
GA AH3TP
UT WOS:000336048700005
PM 24682681
ER
PT J
AU Sparks, SE
Wassif, CA
Goodwin, H
Conley, SK
Lanham, DC
Kratz, LE
Hyland, K
Gropman, A
Tierney, E
Porter, FD
AF Sparks, S. E.
Wassif, C. A.
Goodwin, H.
Conley, S. K.
Lanham, D. C.
Kratz, L. E.
Hyland, K.
Gropman, A.
Tierney, E.
Porter, F. D.
TI Decreased cerebral spinal fluid neurotransmitter levels in
Smith-Lemli-Opitz syndrome
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID HUMAN SEROTONIN(1A) RECEPTOR; CEREBROSPINAL-FLUID;
CHOLESTEROL-BIOSYNTHESIS; LIGAND-BINDING; OPTIZ-SYNDROME; MOUSE MODEL;
7-DEHYDROCHOLESTEROL; BEHAVIOR; AUTISM; METABOLITES
AB Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital anomaly syndrome with cognitive impairment and a distinct behavioral phenotype that includes autistic features. SLOS is caused by a defect in 3 beta-hydroxysterol Delta(7)-reductase which leads to decreased cholesterol levels and elevated cholesterol precursors, specifically 7- and 8-dehydrocholesterol. However, the pathological processes contributing to the neurological abnormalities in SLOS have not been defined. In view of prior data suggesting defects in SLOS in vesicular release and given the association of altered serotonin metabolism with autism, we were interested in measuring neurotransmitter metabolite levels in SLOS to assess their potential to be used as biomarkers in therapeutic trials. We measured cerebral spinal fluid levels of serotonin and dopamine metabolites, 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) respectively, in 21 SLOS subjects. Results were correlated with the SLOS anatomical severity score, Aberrant Behavior Checklist scores and concurrent sterol biochemistry. Cerebral spinal fluid (CSF) levels of both 5HIAA and HVA were significantly reduced in SLOS subjects. In individual patients, the levels of both 5HIAA and HVA were reduced to a similar degree. CSF neurotransmitter metabolite levels did not correlate with either CSF sterols or behavioral measures. This is the first study demonstrating decreased levels of CSF neurotransmitter metabolites in SLOS. We propose that decreased levels of neurotransmitters in SLOS are caused by a sterol-related defect in synaptic vesicle formation and that CSF 5HIAA and HVA will be useful biomarkers in development of future therapeutic trials.
C1 [Sparks, S. E.] Carolinas Med Ctr, Dept Pediat, Charlotte, NC 28203 USA.
[Wassif, C. A.; Goodwin, H.; Conley, S. K.; Porter, F. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Lanham, D. C.; Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Kratz, L. E.] Kennedy Krieger Inst, Biochem Genet Lab, Baltimore, MD USA.
[Hyland, K.] Med Neurogenet, Atlanta, GA USA.
[Gropman, A.] Childrens Natl Med Ctr, Ctr Neurosci Res, Washington, DC 20010 USA.
RP Porter, FD (reprint author), 10 CRC,Rm 5-2571,10 Ctr Dr, Bethesda, MD 20892 USA.
EM fdporter@mail.nih.gov
OI Wassif, Christopher/0000-0002-2524-1420
FU National Institute of Child Health and Human Development; Office of Rare
Diseases; NIH Clinical Center; National Center for Advancing
Translational Sciences (NCATS) a component of the National Institutes of
Health (NIH) [UL1 TR 000424-06]; NIH Roadmap for Medical Research
FX This work was supported by the intramural program of the National
Institute of Child Health and Human Development and a Bench-to-Bedside
award from the Office of Rare Diseases and the NIH Clinical Center.
Autism Speaks, the Johns Hopkins Institute for Clinical and
Translational Research (ICTR) which is funded in part by Grant Number
UL1 TR 000424-06 from the National Center for Advancing Translational
Sciences (NCATS) a component of the National Institutes of Health (NIH),
and NIH Roadmap for Medical Research. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official view of the Johns Hopkins ICTR, NCATS or NIH. We would like to
thank Richard Kelly for critical review of this manuscript. We would
like to express our appreciation to the patients and families that
participated in this study.
NR 35
TC 5
Z9 5
U1 0
U2 4
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 MAY
PY 2014
VL 37
IS 3
BP 415
EP 420
DI 10.1007/s10545-013-9672-5
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA AG9NH
UT WOS:000335745700011
PM 24500076
ER
PT J
AU Trakadis, YJ
Alfares, A
Bodamer, OA
Buyukavci, M
Christodoulou, J
Connor, P
Glamuzina, E
Gonzalez-Fernandez, F
Bibi, H
Echenne, B
Manoli, I
Mitchell, J
Nordwall, M
Prasad, C
Scaglia, F
Schiff, M
Schrewe, B
Touati, G
Tchan, MC
Varet, B
Venditti, CP
Zafeiriou, D
Rupar, CA
Rosenblatt, DS
Watkins, D
Braverman, N
AF Trakadis, Y. J.
Alfares, A.
Bodamer, O. A.
Buyukavci, M.
Christodoulou, J.
Connor, P.
Glamuzina, E.
Gonzalez-Fernandez, F.
Bibi, H.
Echenne, B.
Manoli, I.
Mitchell, J.
Nordwall, M.
Prasad, C.
Scaglia, F.
Schiff, M.
Schrewe, B.
Touati, G.
Tchan, M. C.
Varet, B.
Venditti, C. P.
Zafeiriou, D.
Rupar, C. A.
Rosenblatt, D. S.
Watkins, D.
Braverman, N.
TI Update on transcobalamin deficiency: clinical presentation, treatment
and outcome
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID II DEFICIENCY; FOLLOW-UP; PATIENT; FAMILY; ANEMIA; SERUM
AB Transcobalamin (TC) transports cobalamin from blood into cells. TC deficiency is a rare autosomal recessive disorder usually presenting in early infancy with failure to thrive, weakness, diarrhoea, pallor, anemia, and pancytopenia or agammaglobulinemia. It can sometimes resemble neonatal leukemia or severe combined immunodeficiency disease. Diagnosis of TC deficiency is suspected based on megaloblastic anemia, elevation of total plasma homocysteine, and blood or urine methylmalonic acid. It is confirmed by studying the synthesis of TC in cultured fibroblasts, or by molecular analysis of the TCN2 gene. TC deficiency is treatable with supplemental cobalamin, but the optimal type, route and frequency of cobalamin administration and long term patient outcomes are unknown. Here we present a series of 30 patients with TC deficiency, including an update on multiple previously published patients, in order to evaluate the different treatment strategies and provide information about long term outcome. Based on the data presented, current practice appears to favour treatment of individuals with TC deficiency by intramuscular injections of hydroxy- or cyanocobalamin. In most cases presented, at least weekly injections (1 mg IM) were necessary to ensure optimal treatment. Most centres adjusted the treatment regimen based on monitoring CBC, total plasma homocysteine, plasma and urine methylmalonic acid, as well as, clinical status. Finally, continuing IM treatment into adulthood appears to be beneficial.
C1 [Trakadis, Y. J.; Alfares, A.; Mitchell, J.; Schrewe, B.; Rosenblatt, D. S.; Watkins, D.; Braverman, N.] McGill Univ Hlth Ctr, Dept Med Genet, Montreal, PQ, Canada.
[Bodamer, O. A.] Univ Miami, Dept Human Genet, Miami, FL USA.
[Bodamer, O. A.] Univ Miami, Dept Biochem, Miami, FL USA.
[Bodamer, O. A.] Univ Miami, Dept Mol Biol, Miami, FL USA.
[Buyukavci, M.] Ataturk Univ, Fac Med, Div Pediat Hematol Oncol Erzurum, Erzurum, Turkey.
[Christodoulou, J.] Univ Sydney, Western Sydney Genet Program, Childrens Hosp Westmead, Sydney, NSW 2006, Australia.
[Christodoulou, J.] Univ Sydney, Discipline Genet Med, Sydney, NSW 2006, Australia.
[Christodoulou, J.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia.
[Connor, P.] Childrens Hosp Wales Heath Pk, Dept Haematol, Cardiff, S Glam, Wales.
[Glamuzina, E.] Starship Childrens Hosp, Adult & Paediat Natl Metab Serv, Auckland, New Zealand.
[Gonzalez-Fernandez, F.] Hosp Clin San Carlos Madrid, Secc Eritropatol, Serv Hematol & Hemoterapia, Madrid, Spain.
[Bibi, H.] Ben Gurion Univ Negev, Dept Pediat, Barzilai Med Ctr, IL-84105 Beer Sheva, Israel.
[Echenne, B.] Hop Gui De Chauliac, Serv Neuropediat, F-34295 Montpellier, France.
[Manoli, I.; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Nordwall, M.] Vrinnevi Hosp, Div Paediat, Norrkoping, County Of Oster, Sweden.
[Prasad, C.] London Hlth Sci Ctr, Dept Pediat, London, ON, Canada.
[Prasad, C.] Western Univ London, London, ON, Canada.
[Scaglia, F.] Baylor Coll Med, Dept Mol Genet, Houston, TX 77030 USA.
[Scaglia, F.] Baylor Coll Med, Dept Human Genet, Houston, TX 77030 USA.
[Schiff, M.] Hop Robert Debre, Reference Ctr Metab Dis, F-75019 Paris, France.
[Touati, G.] Univ Paris 05, Necker Enfants Malades Hosp, AP HP, Ctr Inherited Metab Disorders, Paris, France.
[Tchan, M. C.] Westmead Hosp, Dept Med Genet, Sydney, NSW, Australia.
[Tchan, M. C.] Univ Sydney, Sydney Med Sch, Discipline Genet Med, Sydney, NSW 2006, Australia.
[Varet, B.] Paris Descartes Univ, Necker Hosp, Dept Hematol, Paris, France.
[Zafeiriou, D.] Aristotle Univ Thessaloniki, Dept Paediat, Hippokrat Gen Hosp, GR-54006 Thessaloniki, Greece.
[Rupar, C. A.] Univ Western Ontario, Dept Biochem, London, ON, Canada.
[Rupar, C. A.] Univ Western Ontario, Dept Pediat, London, ON N6A 3K7, Canada.
[Rupar, C. A.] Univ Western Ontario, Childrens Hlth Res Inst, London, ON, Canada.
[Trakadis, Y. J.] McGill Univ Hlth Ctr, Montreal Childrens Hosp, Montreal, PQ, Canada.
RP Trakadis, YJ (reprint author), McGill Univ Hlth Ctr, Montreal Childrens Hosp, Montreal, PQ, Canada.
EM john.trakadis@mail.mcgill.ca
RI Christodoulou, John/E-5866-2015;
OI Manoli, Irini/0000-0003-1543-2941; Christodoulou,
John/0000-0002-8431-0641
NR 29
TC 8
Z9 8
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 MAY
PY 2014
VL 37
IS 3
BP 461
EP 473
DI 10.1007/s10545-013-9664-5
PG 13
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA AG9NH
UT WOS:000335745700017
PM 24305960
ER
PT J
AU Buxton, DB
AF Buxton, Denis B.
TI Noninvasive Measurement of Mouse Myocardial Glucose Uptake with F-18-FDG
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Letter
ID NONPRIMATE ERYTHROCYTES; PERMEABILITY; METABOLISM; PET
C1 NHLBI, Bethesda, MD 20892 USA.
RP Buxton, DB (reprint author), NHLBI, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM db225a@nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 3
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 MAY
PY 2014
VL 55
IS 5
BP 866
EP 866
DI 10.2967/jnumed.113.135152
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH2RF
UT WOS:000335968000037
PM 24652831
ER
PT J
AU Yang, JC
Sherry, RM
Rosenberg, SA
AF Yang, James C.
Sherry, Richard M.
Rosenberg, Steven A.
TI Why is sentinel lymph node biopsy 'standard of care' for melanoma?
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID GUIDELINES
AB A large definitive trial comparing the use of sentinel lymph node biopsy and elective lymph node dissection to observation in patients with intermediate thickness melanomas fails to show improved melanoma-specific survival. These results demand reconsideration of the routine use of sentinel lymph node biopsy in the treatment of primary melanoma.
C1 [Yang, James C.; Sherry, Richard M.; Rosenberg, Steven A.] NCI, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Ctr Canc Res, Surg Branch, CRC Room 3-5952,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sar@mail.nih.gov
NR 9
TC 6
Z9 6
U1 0
U2 2
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 MAY
PY 2014
VL 11
IS 5
BP 245
EP 246
DI 10.1038/nrclinonc.2014.65
PG 2
WC Oncology
SC Oncology
GA AH1VL
UT WOS:000335909200002
PM 24732941
ER
PT J
AU Adewole, I
Martin, DN
Williams, MJ
Adebamowo, C
Bhatia, K
Berling, C
Casper, C
Elshamy, K
Elzawawy, A
Lawlor, RT
Legood, R
Mbulaiteye, SM
Odedina, FT
Olopade, OI
Olopade, CO
Parkin, DM
Rebbeck, TR
Ross, H
Santini, LA
Torode, J
Trimble, EL
Wild, CP
Young, AM
Kerr, DJ
AF Adewole, Isaac
Martin, Damali N.
Williams, Makeda J.
Adebamowo, Clement
Bhatia, Kishor
Berling, Christine
Casper, Corey
Elshamy, Karima
Elzawawy, Ahmed
Lawlor, Rita T.
Legood, Rosa
Mbulaiteye, Sam M.
Odedina, Folakemi T.
Olopade, Olufunmilayo I.
Olopade, Christopher O.
Parkin, Donald M.
Rebbeck, Timothy R.
Ross, Hana
Santini, Luiz A.
Torode, Julie
Trimble, Edward L.
Wild, Christopher P.
Young, Annie M.
Kerr, David J.
TI Building capacity for sustainable research programmes for cancer in
Africa
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID SUB-SAHARAN AFRICA; GAMBIA HEPATITIS INTERVENTION; BURKITT-LYMPHOMA;
BREAST-CANCER; DEVELOPING-COUNTRIES; CERVICAL-CANCER; CLINICAL-TRIALS;
HEALTH RESEARCH; KAPOSI-SARCOMA; NIGERIAN WOMEN
AB Cancer research in Africa will have a pivotal role in cancer control planning in this continent. However, environments (such as those in academic or clinical settings) with limited research infrastructure (laboratories, biorespositories, databases) coupled with inadequate funding and other resources have hampered African scientists from carrying out rigorous research. In September 2012, over 100 scientists with expertise in cancer research in Africa met in London to discuss the challenges in performing high-quality research, and to formulate the next steps for building sustainable, comprehensive and multi-disciplinary programmes relevant to Africa. This was the first meeting among five major organizations: the African Organisation for Research and Training in Africa (AORTIC), the Africa Oxford Cancer Foundation (AfrOx), and the National Cancer Institutes (NCI) of Brazil, France and the USA. This article summarizes the discussions and recommendations of this meeting, including the next steps required to create sustainable and impactful research programmes that will enable evidenced- based cancer control approaches and planning at the local, regional and national levels.
C1 [Adewole, Isaac] Univ Ibadan, Coll Med, Dept Obster & Gynecol, Gynecol Oncol Unit, Ibadan, Nigeria.
[Martin, Damali N.; Williams, Makeda J.; Mbulaiteye, Sam M.; Trimble, Edward L.] NIH, Bethesda, MD 20892 USA.
[Adebamowo, Clement] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Bhatia, Kishor] NCI, Bethesda, MD 20892 USA.
[Casper, Corey] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Elzawawy, Ahmed] Mansoura Univ, Mansoura, Egypt.
[Lawlor, Rita T.] ARC NET Canc Res Ctr, Verona, Italy.
[Legood, Rosa] London Sch Hyg & Trop Med, London, England.
[Odedina, Folakemi T.] Univ Florida, Gainesville, FL 32611 USA.
[Rebbeck, Timothy R.] Univ Penn, Philadelphia, PA 19104 USA.
[Ross, Hana] Amer Canc Soc, Atlanta, GA 30329 USA.
[Torode, Julie] Union Int Canc Control, Geneva, Switzerland.
[Young, Annie M.] Univ Warwick, Coventry CV4 7AL, W Midlands, England.
[Kerr, David J.] Univ Oxford, Oxford OX1 2JD, England.
RP Adewole, I (reprint author), Univ Ibadan, Coll Med, Dept Obster & Gynecol, Gynecol Oncol Unit, PMB 5017,GPO, Ibadan, Nigeria.
EM if.adewole@mail.ui.edu.ng
OI lawlor, Rita/0000-0003-3160-0634
FU FIC NIH HHS [R25 TW007091]; Intramural NIH HHS [Z01 CP010150-08]
NR 84
TC 14
Z9 14
U1 1
U2 9
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 MAY
PY 2014
VL 11
IS 5
BP 251
EP 259
DI 10.1038/nrclinonc.2014.37
PG 9
WC Oncology
SC Oncology
GA AH1VL
UT WOS:000335909200005
PM 24614139
ER
PT J
AU Lake, CR
AF Lake, C. Ray
TI This issue: Justification for Breaking the Goldwater Rule: Mass
Murderers' Diagnoses
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Lake, C. Ray] Univ Kansas, Sch Med, Kansas City, KS 66103 USA.
[Lake, C. Ray] NIMH, Clin Sci Lab, Bethesda, MD USA.
[Lake, C. Ray] Uniformed Serv Univ Hlth Sci, Sch Med, Bethesda, MD 20814 USA.
RP Lake, CR (reprint author), Univ Kansas, Sch Med, Kansas City, KS 66103 USA.
NR 4
TC 0
Z9 0
U1 0
U2 1
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
EI 1938-2456
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD MAY
PY 2014
VL 44
IS 5
BP 211
EP 212
DI 10.3928/00485713-20140502-03
PG 2
WC Psychiatry
SC Psychiatry
GA AH2LK
UT WOS:000335952700003
ER
PT J
AU Merikangas, KR
Zhang, J
Emsellem, H
Swanson, SA
Vgontzas, A
Belouad, F
Blank, MM
Chen, W
Einen, M
He, JP
Heaton, L
Nakamura, E
Rooholamini, S
Mignot, E
AF Merikangas, K. R.
Zhang, J.
Emsellem, H.
Swanson, S. A.
Vgontzas, A.
Belouad, F.
Blank, M. M.
Chen, W.
Einen, M.
He, J. P.
Heaton, L.
Nakamura, E.
Rooholamini, S.
Mignot, E.
TI The structured Diagnostic Interview for Sleep Patterns and Disorders:
rationale and initial evaluation
SO SLEEP MEDICINE
LA English
DT Article
DE Diagnostic Interview; Sleep disorders; Validity; International
Classification of Sleep Disorders; Concordance; Area under the curve
(AUC)
ID RESTLESS LEGS SYNDROME; GENERAL-POPULATION; SEVERE INSOMNIA;
RISK-FACTORS; PREVALENCE; EPIDEMIOLOGY; ADULTS; APNEA; COMMUNITY; HEALTH
AB Objectives: We aimed to describe and report the initial validity of a newly developed structured interview for sleep disorders (Diagnostic Interview for Sleep Patterns and Disorders [DISP]) administered by trained lay interviewers.
Methods: A total of 225 patients with various sleep disorders were recruited from two nationally recognized sleep centers in the United States. The International Classification of Sleep Disorders, second edition (ICSD-2) criteria, were used to classify sleep disorders (e.g., delayed sleep phase disorder, hypersomnia, narcolepsy with cataplexy [NC], restless legs syndrome [RLS], periodic limb movement disorder [PLMD], insomnia, rapid eye movement sleep behavior disorder [RBD], and obstructive sleep apnea [OSA]). Interview diagnoses were compared with final diagnoses by sleep specialists (reference diagnosis based on clinical history, examination, and polysomnography [PSG] when indicated).
Results: DISP diagnoses had fair to substantial concordance with clinician diagnoses for various sleep disorders, with area under the receiver operator characteristic curves (AUC) ranging from 0.65 to 0.84. Participants classified by the clinician as having a sleep disorder were moderately well-detected (sensitivity ranging from 0.50 for RBD disorder to 0.87 for insomnia). Substantial specificity (> 0.8) also was seen for five of the eight sleep disorders (i.e., delayed sleep phase, hypersomnia, NC, PLMD, and RBD). Interviews were more likely than clinicians to detect disorders secondary to the primary sleep problem.
Conclusions: The DISP provides an important tool for the detection of a wide range of sleep disorders in clinical settings and is particularly valuable in the detection of secondary disorders that were not the primary referral diagnosis. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Merikangas, K. R.; Zhang, J.; Belouad, F.; Blank, M. M.; He, J. P.; Heaton, L.; Nakamura, E.] NIMH, Genet Epidemiol Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Emsellem, H.] Ctr Sleep & Wake Disorders, Chevy Chase, MD USA.
[Swanson, S. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Vgontzas, A.] Penn State Coll Med, Hershey, PA USA.
[Chen, W.; Einen, M.; Rooholamini, S.; Mignot, E.] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM Kathleen.merikangas@nih.gov
FU Intramural Research Program of the National Institute of Mental Health
[Z01 MH002804]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health (Z01 MH002804). The views and
opinions expressed in this article are those of the authors and should
not be construed to represent the views of any of the sponsoring
organizations, agencies, or US Government.
NR 53
TC 3
Z9 3
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD MAY
PY 2014
VL 15
IS 5
BP 530
EP 535
DI 10.1016/j.sleep.2013.10.011
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA AH1YI
UT WOS:000335917400009
PM 24780136
ER
PT J
AU Eitan, E
Hutchison, ER
Mattson, MP
AF Eitan, Erez
Hutchison, Emmette R.
Mattson, Mark P.
TI Telomere shortening in neurological disorders: an abundance of
unanswered questions
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID MILD COGNITIVE IMPAIRMENT; PARKINSONS-DISEASE PATIENTS; OXIDATIVE
DNA-DAMAGE; WHITE BLOOD-CELLS; ALZHEIMERS-DISEASE; OLDER INDIVIDUALS;
DOWN-SYNDROME; HUMAN T; NEURODEGENERATIVE DISEASES; LYMPHOCYTE
SUBPOPULATIONS
AB Telomeres, ribonucleoprotein complexes that cap eukaryotic chromosomes, typically shorten in leukocytes with aging. Aging is a primary risk factor for neurodegenerative disease (ND), and a common assumption has arisen that leukocyte telomere length (LTL) can serve as a predictor of neurological disease. However, the evidence for shorter LTL in Alzheimer's and Parkinson's patients is inconsistent. The diverse causes of telomere shortening may explain variability in LTL between studies and individuals. Additional research is needed to determine whether neuronal and glial telomeres shorten during aging and in neurodegenerative disorders, if and how LTL is related to brain cell telomere shortening, and whether telomere shortening plays a causal role in or exacerbates neurological disorders.
C1 [Eitan, Erez; Hutchison, Emmette R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mark.mattson@nih.gov
FU Intramural Research Program of the National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institute on Aging.
NR 102
TC 23
Z9 23
U1 4
U2 15
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD MAY
PY 2014
VL 37
IS 5
BP 256
EP 263
DI 10.1016/j.tins.2014.02.010
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AH4QS
UT WOS:000336113700003
PM 24698125
ER
PT J
AU Richardson, VM
Ferguson, SS
Sey, YM
DeVito, MJ
AF Richardson, Vicki M.
Ferguson, Stephen S.
Sey, Yusupha M.
DeVito, Michael J.
TI In vitro metabolism of thyroxine by rat and human hepatocytes
SO XENOBIOTICA
LA English
DT Article
DE Deiodination; glucuronidation; PCB 153; sulfation; thyroid hormone; T-4
ID MICROSOMAL-ENZYME INDUCERS; UDP-GLUCURONOSYLTRANSFERASE INDUCERS;
FOLLICULAR CELL-PROLIFERATION; THYROID-HORMONE METABOLISM;
POLYCHLORINATED BIPHENYL CONGENERS; BILIARY-EXCRETION; IODOTHYRONINE
SULFOTRANSFERASES; CYTOCHROME-P450 ENZYMES; TRIIODOTHYRONINE T-3;
GENE-EXPRESSION
AB 1. The liver metabolizes thyroxine (T-4) through two major pathways: deiodination and conjugation. Following exposure to xenobiotics, T-4 conjugation increases through the induction of hepatic uridine diphosphate glucuronosyltransferase (UGT) in rodents; however, it is uncertain to what degree different species employ deiodination and conjugation in the metabolism of T-4. The objective of this study was to compare the metabolism of T-4 in untreated and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153)-treated primary sandwich-cultured hepatocytes from rat (SCRH) and human (SCHH).
2. Basal metabolite concentrations were 13 times higher in the medium of SCRH compared to SCHH. Metabolite distribution in the medium of SCRH versus SCHH was as follows: T(4)G, (91.6 versus 5.3%); T4S, (3.6 versus 4.4%) and T-3+rT(3), (4.9 versus 90.3%). PCB 153 induced T(4)G in the medium of SCRH and SCHH; however, T4S and T-3+rT(3) were changed but to a much lesser degree.
3. The results indicate that baseline T-4 glucuronidation is greater in SCRH compared to SCHH. These data also suggest that glucuronidation may be a more important pathway for T4 metabolism in rats and deiodination may be a favored pathway in humans; however, with PCB 153 treatment these data support glucuronidation as a primary route of T-4 metabolism in both rat and humans.
C1 [Richardson, Vicki M.; Sey, Yusupha M.] US EPA, Pharmacokinet Branch, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27709 USA.
[Richardson, Vicki M.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA.
[Ferguson, Stephen S.] Life Technol, Durham, NC USA.
[DeVito, Michael J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Richardson, VM (reprint author), US EPA, Pharmacokinet Branch, Integrated Syst Toxicol Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, MD B105-03, Res Triangle Pk, NC 27709 USA.
EM richardson.vicki@epa.gov
NR 64
TC 6
Z9 7
U1 0
U2 15
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0049-8254
EI 1366-5928
J9 XENOBIOTICA
JI Xenobiotica
PD MAY
PY 2014
VL 44
IS 5
BP 391
EP 403
DI 10.3109/00498254.2013.847990
PG 13
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA AH1OW
UT WOS:000335891600001
PM 24175917
ER
PT J
AU Kudenchuk, PJ
Brown, SP
Daya, M
Morrison, LJ
Grunau, BE
Rea, T
Aufderheide, T
Powell, J
Leroux, B
Vaillancourt, C
Larsen, J
Wittwer, L
Colella, MR
Stephens, SW
Gamber, M
Egan, D
Dorian, P
AF Kudenchuk, Peter J.
Brown, Siobhan P.
Daya, Mohamud
Morrison, Laurie J.
Grunau, Brian E.
Rea, Tom
Aufderheide, Tom
Powell, Judy
Leroux, Brian
Vaillancourt, Christian
Larsen, Jonathan
Wittwer, Lynn
Colella, M. Riccardo
Stephens, Shannon W.
Gamber, Mark
Egan, Debra
Dorian, Paul
TI Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study
(ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac
arrest antiarrhythmic drug trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID AMERICAN-HEART-ASSOCIATION; DEFIBRILLATION ENERGY-REQUIREMENTS;
EMERGENCY CARDIOVASCULAR CARE; INTERNATIONAL LIAISON COMMITTEE;
VENTRICULAR-FIBRILLATION; INTRAVENOUS AMIODARONE;
CARDIOPULMONARY-RESUSCITATION; CONSENSUS STATEMENT; STROKE FOUNDATION;
SOUTHERN AFRICA
AB Background Despite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT).
Methods ALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after >= 1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score <= 3.
Results The principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating.
Conclusions Results from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice.
C1 [Kudenchuk, Peter J.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA.
[Kudenchuk, Peter J.] Publ Hlth Seattle & King Cty, Seattle, WA USA.
[Brown, Siobhan P.; Powell, Judy; Leroux, Brian] Univ Washington, Dept Biostat, Clin Trial Ctr, Seattle, WA 98195 USA.
[Daya, Mohamud] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA.
[Morrison, Laurie J.] Univ Toronto, St Michaels Hosp, Dept Med, ERESCU,Keenan Res Ctr,Div Emergency Med, Toronto, ON M5B 1W8, Canada.
[Grunau, Brian E.] Univ British Columbia, Dept Emergency Med, Vancouver, BC V5Z 1M9, Canada.
[Rea, Tom] Univ Washington, Dept Med, Seattle, WA USA.
[Aufderheide, Tom] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Vaillancourt, Christian] Univ Ottawa, Ottawa Hosp Res Inst, Dept Emergency Med, Ottawa, ON K1N 6N5, Canada.
[Larsen, Jonathan] Seattle Fire Dept, Seattle, WA USA.
[Wittwer, Lynn] Peace Hlth Southwest Med Ctr, Vancouver, WA USA.
[Colella, M. Riccardo] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA.
[Stephens, Shannon W.] Univ Alabama Birmingham, Dept Emergency Med, Birmingham, AL USA.
[Gamber, Mark] Plano Fire Rescue, Plano, TX USA.
[Egan, Debra] NHLBI, NIH, Bethesda, MD 20892 USA.
[Dorian, Paul] Univ Toronto, St Michaels Hosp, Dept Med, Div Cardiol, Toronto, ON M5B 1W8, Canada.
RP Kudenchuk, PJ (reprint author), Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA.
EM kudenchuk@u.washington.edu
RI Leroux, Brian/H-2254-2015; morrison, laurie/A-6325-2012;
OI morrison, laurie/0000-0001-8369-9774; Stephens,
Shannon/0000-0001-5898-5170; Brown, Siobhan/0000-0002-4774-3122;
Welsford, Michelle/0000-0003-2682-641X; Ferguson,
Niall/0000-0002-6213-5264; Guffey, Danielle/0000-0003-3721-614X
FU Canadian Institutes of Health Research; NHLBI NIH HHS [U01 HL077873,
5U01 HL077863, HL077866, HL077867, HL077871, HL077872, HL077873,
HL077881, HL077885, HL077887, HL077908, U01 HL077863, U01 HL077866, U01
HL077867, U01 HL077871, U01 HL077872, U01 HL077881, U01 HL077885, U01
HL077887, U01 HL077908]
NR 47
TC 24
Z9 24
U1 1
U2 16
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 MAY
PY 2014
VL 167
IS 5
BP 653
EP U40
DI 10.1016/j.ahj.2014.02.010
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AG5GP
UT WOS:000335447800004
PM 24766974
ER
PT J
AU Rosenberg, MA
Maziarz, M
Tan, AY
Glazer, NL
Zieman, SJ
Kizer, JR
Ix, JH
Djousse, L
Siscovick, DS
Heckbert, SR
Mukamal, KJ
AF Rosenberg, Michael A.
Maziarz, Marlena
Tan, Alex Y.
Glazer, Nicole L.
Zieman, Susan J.
Kizer, Jorge R.
Ix, Joachim H.
Djousse, Luc
Siscovick, David S.
Heckbert, Susan R.
Mukamal, Kenneth J.
TI Circulating fibrosis biomarkers and risk of atrial fibrillation: The
Cardiovascular Health Study (CHS)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID GROWTH-FACTOR BETA-1; HEART-FAILURE; STRUCTURAL ABNORMALITIES; CARDIAC
FIBROSIS; III PROCOLLAGEN; OLDER-ADULTS; MODEL; AGE; OVEREXPRESSION;
CARDIOMYOPATHY
AB Background Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited.
Methods We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor beta 1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years.
Results Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 mu g/L), adjusted hazard ratios (95% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor beta 1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk.
Conclusion In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship.
C1 [Rosenberg, Michael A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Div Cardiac Electrophysiol, Boston, MA USA.
[Rosenberg, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA.
[Maziarz, Marlena] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Tan, Alex Y.] Virginia Commonwealth Univ, Div Electrophysiol, Richmond, VA USA.
[Glazer, Nicole L.] Merck Pharmaceut, Translat & Hlth Informat, Boston, MA USA.
[Zieman, Susan J.] NIA, Dept Med, Div Cardiol, Johns Hopkins Med Inst, Baltimore, MD 21224 USA.
[Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA.
[Djousse, Luc] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA.
[Djousse, Luc] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst, Boston, MA USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Mukamal, Kenneth J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA.
[Mukamal, Kenneth J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Epidemiol, Boston, MA 02215 USA.
RP Rosenberg, MA (reprint author), 1400 VFW Pkwy,111CA, Boston, MA 02132 USA.
EM Michael.rosenberg@va.gov
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU NHLBI NIH HHS [U01 HL080295, HHSN268200800007C, HHSN268201200036C,
N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083,
N01HC85086, R01 HL080295]; NIA NIH HHS [R01 AG023629, R56 AG023629]
NR 45
TC 8
Z9 9
U1 0
U2 2
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 MAY
PY 2014
VL 167
IS 5
BP 723
EP U114
AR 723-728.e2
DI 10.1016/j.ahj.2014.01.010
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AG5GP
UT WOS:000335447800013
PM 24766983
ER
PT J
AU Ho, JE
Yin, XY
Levy, D
Vasan, RS
Magnani, JW
Ellinor, PT
McManus, DD
Lubitz, SA
Larson, MG
Benjamin, EJ
AF Ho, Jennifer E.
Yin, Xiaoyan
Levy, Daniel
Vasan, Ramachandran S.
Magnani, Jared W.
Ellinor, Patrick T.
McManus, David D.
Lubitz, Steven A.
Larson, Martin G.
Benjamin, Emelia J.
TI Galectin 3 and incident atrial fibrillation in the community
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CONGESTIVE-HEART-FAILURE; PREDICTING STROKE; FIBROSIS; FRAMINGHAM;
DYSFUNCTION; MARKER; RISK; OVEREXPRESSION; EPIDEMIOLOGY; MACROPHAGES
AB Background Galectin 3 (Gal-3) is a potential mediator of cardiac fibrosis, and Gal-3 concentrations predict incident heart failure. The same mechanisms that lead to cardiac fibrosis in heart failure may influence development of atrial fibrosis and atrial fibrillation (AF). We examined the association of Gal-3 and incident AF in the community.
Methods Plasma Gal-3 concentrations were measured in 3,306 participants of the Framingham Offspring cohort who attended the sixth examination cycle (1995-1998, mean age 58 years, 54% women). Cox proportional hazards regression models were used to assess the association of baseline Gal-3 concentrations and incident AF.
Results Over a median follow-up period of 10 years, 250 participants developed incident AF. Crude incidence rates of AF by increasing sex-specific Gal-3 quartiles were 3.7%, 5.9%, 9.1%, and 11.5% (log-rank test P < .0001). In age-and sex-adjusted analyses, each 1-SD increase in log(e)-Gal-3 was associated with a 19% increased hazard of incident AF (hazard ratio 1.19, 95% CI 1.05-1.36, P = .009). This association was not significant after adjustment for traditional clinical AF risk factors (hazard ratio 1.12, 95% CI 0.98-1.28, P = .10).
Conclusion Higher circulating Gal-3 concentrations were associated with increased risk of developing AF over the subsequent 10 years in age-and sex-adjusted analyses but not after accounting for other traditional clinical AF risk factors. Our results do not support a role for Gal-3 in AF risk prediction. Further studies are needed to evaluate whether Gal-3 plays a role in the development of AF substrate similar to HF.
C1 [Ho, Jennifer E.; Yin, Xiaoyan; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Framingham, MA USA.
[Ho, Jennifer E.; Yin, Xiaoyan; Levy, Daniel; Vasan, Ramachandran S.; Magnani, Jared W.; McManus, David D.; Larson, Martin G.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ho, Jennifer E.; Magnani, Jared W.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02459 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02459 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02459 USA.
[Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Ellinor, Patrick T.; Lubitz, Steven A.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiovasc Med, Worcester, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02459 USA.
RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02459 USA.
EM jenho@bu.edu
OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU NCRR NIH HHS [KL2 RR031981]; NHLBI NIH HHS [K23 HL116780, K24 HL105780,
N01 HC025195, R01 HL092577, R01 HL102214, RC1 HL101056, U01 HL105268];
NINDS NIH HHS [R01 NS017950]
NR 38
TC 27
Z9 28
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 MAY
PY 2014
VL 167
IS 5
BP 729
EP U121
AR 729-734.e1
DI 10.1016/j.ahj.2014.02.009
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AG5GP
UT WOS:000335447800014
PM 24766984
ER
PT J
AU Pavkov, ME
Nelson, RG
AF Pavkov, Meda E.
Nelson, Robert G.
TI Improved Early Risk Stratification With Cystatin C-Based Estimated GFR
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Editorial Material
ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; COLLABORATIVE
METAANALYSIS; ESTIMATING EQUATIONS; POPULATION COHORTS; MORTALITY;
ALBUMINURIA; ASSOCIATION
C1 [Pavkov, Meda E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Nelson, Robert G.] NIH, Phoenix, AZ 85014 USA.
RP Nelson, RG (reprint author), NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM rnelson@nih.gov
NR 27
TC 0
Z9 0
U1 0
U2 2
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 MAY
PY 2014
VL 63
IS 5
BP 745
EP 748
DI 10.1053/j.ajkd.2014.02.006
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA AG5JZ
UT WOS:000335456600416
PM 24602780
ER
PT J
AU Chapman, AB
Gibbs, P
Rahbari-Oskoui, F
Bae, T
Bhutani, HS
Grantham, J
Harris, P
Mrug, M
Torres, V
Yu, A
Flessner, M
Landsittel, D
AF Chapman, Arlene B.
Gibbs, Patrice
Rahbari-Oskoui, Frederic
Bae, Ty
Bhutani, Harpreet Singh
Grantham, Jared
Harris, Peter
Mrug, Michal
Torres, Vicente
Yu, Alan
Flessner, Micheal
Landsittel, Doug
TI CHARACTERISTICS OF ADPKD PATIENTS WITH RAPID PROGRESSION TO RENAL
FAILURE: LESSONS FROM CRISP.
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Meeting Abstract
CT Spring Clinical Meeting of the National-Kidney-Foundation (NKF)
CY APR 22-26, 2014
CL Las Vegas, NV
SP Natl Kidney Fdn
C1 [Chapman, Arlene B.; Rahbari-Oskoui, Frederic; Bhutani, Harpreet Singh] Emory Univ, Atlanta, GA 30322 USA.
[Gibbs, Patrice; Bae, Ty; Landsittel, Doug] Univ Pittsburgh, Pittsburgh, PA USA.
[Grantham, Jared; Yu, Alan] Univ Kansas, Med Ctr, Lawrence, KS 66045 USA.
[Mrug, Michal] Univ Alabama Birmingham, Birmingham, AL USA.
[Flessner, Micheal] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY
PY 2014
VL 63
IS 5
MA 74
BP A37
EP A37
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA AG5JZ
UT WOS:000335456600076
ER
PT J
AU Reddy, UM
Abuhamad, AZ
Levine, D
Saade, GR
AF Reddy, Uma M.
Abuhamad, Alfred Z.
Levine, Deborah
Saade, George R.
CA Fetal Imaging Workshop Invited Par
TI Fetal imaging: Executive Summary of a Joint Eunice Kennedy Shriver
National Institute of Child Health and Human Development, Society for
Maternal-Fetal Medicine, American Institute of Ultrasound in Medicine,
American College of Obstetricians and Gynecologists, American College of
Radiology, Society for Pediatric Radiology, and Society of Radiologists
in Ultrasound Fetal Imaging Workshop
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Review
ID CHOROID-PLEXUS CYSTS; AMNIOTIC-FLUID VOLUME; LOW-LYING PLACENTA;
NERVOUS-SYSTEM ABNORMALITIES; INTRACARDIAC ECHOGENIC FOCI; TWIN
TRANSFUSION SYNDROME; BIRTH-WEIGHT DISCORDANCE; LAST MENSTRUAL PERIOD;
INTERNAL OS DISTANCE; ISOLATED SHORT FEMUR
AB Given that practice variation exists in the frequency and performance of ultrasound and magnetic resonance imaging in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development hosted a workshop to address indications for ultrasound and magnetic resonance imaging in pregnancy, to discuss when and how often these studies should be performed, to consider recommendations for optimizing yield and cost-effectiveness and to identify research opportunities. This article is the executive summary of the workshop.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
Univ Texas Med Branch, Galveston, TX 77555 USA.
RP Reddy, UM (reprint author), 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA.
EM reddyu@mail.nih.gov
NR 116
TC 23
Z9 23
U1 1
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 MAY
PY 2014
VL 210
IS 5
BP 387
EP 397
DI 10.1016/j.ajog.2014.02.028
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AG6EF
UT WOS:000335510700003
PM 24793721
ER
PT J
AU Raju, TNK
Mercer, BM
Burchfield, DJ
Joseph, GF
AF Raju, Tonse N. K.
Mercer, Brian M.
Burchfield, David J.
Joseph, Gerald F., Jr.
TI Periviable birth: executive summary of a joint workshop by the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, Society for Maternal-Fetal Medicine, American Academy of
Pediatrics, and American College of Obstetricians and Gynecologists
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID EXTREMELY PRETERM INFANTS; EXTREMELY PREMATURE-INFANTS; WEEKS
GESTATIONAL-AGE; WEIGHT INFANTS; ANTENATAL CORTICOSTEROIDS; DELIVERY
ROOM; UNITED-STATES; CARDIOPULMONARY-RESUSCITATION; NEURODEVELOPMENTAL
OUTCOMES; EMERGENCY CERCLAGE
AB This is an executive summary of a workshop on the management and counseling issues of women anticipated to deliver at a periviable gestation (broadly defined as 20 0/7 through 25 6/7 weeks of gestation) and the treatment options for the newborn infant. Upon review of the available literature, the workshop panel noted that the rates of neonatal survival and neurodevelopmental disabilities among the survivors vary greatly across the periviable gestations and are significantly influenced by the obstetric and neonatal management practices (eg, antenatal steroid, tocolytic agents, and antibiotic administration; cesarean birth; and local protocols for perinatal care, neonatal resuscitation, and intensive care support). These are, in turn, influenced by the variations in local and regional definitions of limits of viability. Because of the complexities in making difficult management decisions, obstetric and neonatal teams should confer prior to meeting with the family, when feasible. Family counseling should be coordinated with the goal of creating mutual trust, respect, and understanding and should incorporate evidence-based counseling methods. Since clinical circumstances can change rapidly with increasing gestational age, counseling should include discussion of the benefits and risks of various maternal and neonatal interventions at the time of counseling. There should be a plan for follow-up counseling as clinical circumstances evolve. The panel proposed a research agenda and recommended developing educational curricula on the care and counseling of families facing the birth of a periviable infant.
C1 [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
Soc Maternal Fetal Med, Cleveland, OH USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Amer Acad Pediat, Gainesville, FL USA.
Univ Florida, Gainesville, FL USA.
Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA.
RP Raju, TNK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
NR 60
TC 7
Z9 7
U1 0
U2 7
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 MAY
PY 2014
VL 210
IS 5
BP 406
EP 417
DI 10.1016/j.ajog.2014.02.027
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AG6EF
UT WOS:000335510700005
PM 24725732
ER
PT J
AU Boghossian, NS
Yeung, E
Albert, PS
Mendola, P
Laughon, SK
Hinkle, SN
Zhang, CL
AF Boghossian, Nansi S.
Yeung, Edwina
Albert, Paul S.
Mendola, Pauline
Laughon, S. Katherine
Hinkle, Stefanie N.
Zhang, Cuilin
TI Changes in diabetes status between pregnancies and impact on subsequent
newborn outcomes
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE diabetes; large for gestational age; macrosomia; respiratory distress;
shoulder dystocia
ID RISK-FACTORS; PRETERM BIRTH; CARBOHYDRATE INTOLERANCE; MELLITUS; WOMEN;
FETAL; POPULATION; HYPERGLYCEMIA; ASSOCIATION; SECRETION
AB OBJECTIVE: Pregnancies complicated by gestational diabetes mellitus (GDM) or preexisting diabetes mellitus (DM) are at high risk for adverse newborn outcomes. Whether GDM history, recurrence, or transition to DM modifies such risks is unknown.
STUDY DESIGN: Medical record data on 62,013 repeat singleton pregnancies were collected retrospectively from women who delivered at least twice in Utah (2002 through 2010). Poisson regression models with robust variance estimators were used to estimate relative risks (RR) and 95% confidence intervals (CI) associated with GDM/DM status at the previous and/or current pregnancy relative to those without GDM/DM at either. Large for gestational age (LGA), shoulder dystocia, preterm birth (< 37 weeks), respiratory distress syndrome, and other neonatal morbidities were examined adjusting for study site, maternal age, race, parity, interpregnancy interval, prepregnancy body mass index, and smoking status.
RESULTS: GDM in the previous pregnancy alone increased the risk of LGA in the current pregnancy (RR, 1.20; 95% CI, 1.05-1.38). Recurrent GDM increased the risks of LGA (RR, 1.76; 95% CI, 1.56-1.98), shoulder dystocia (RR, 1.98; 95% CI, 1.46-2.70), and preterm birth (RR, 1.68; 95% CI, 1.44-1.96) beyond that observed for pregnancies with current GDM alone. Women with GDM in a previous pregnancy that transitioned to DM in the current pregnancy and women with DM prior to the previous pregnancy had increased risks of all above outcomes.
CONCLUSION: GDM in a previous pregnancy alone without recurrence may still confer an increased LGA risk. Pregnancies complicated by GDM that transition to DM and those with DM prior to the previous pregnancy have the highest risks of adverse newborn outcomes.
C1 [Boghossian, Nansi S.; Yeung, Edwina; Albert, Paul S.; Mendola, Pauline; Laughon, S. Katherine; Hinkle, Stefanie N.; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
RP Boghossian, NS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
RI Yeung, Edwina/F-5992-2015; Hinkle, Stefanie/F-8253-2013;
OI Yeung, Edwina/0000-0002-3851-2613; Hinkle, Stefanie/0000-0003-4312-708X;
Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development [HHSN2752008000021,
HHSN27500004]
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
contract numbers HHSN2752008000021 and HHSN27500004.
NR 31
TC 7
Z9 8
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 MAY
PY 2014
VL 210
IS 5
AR 431.e1
DI 10.1016/j.ajog.2013.12.026
PG 14
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AG6EF
UT WOS:000335510700010
PM 24361790
ER
PT J
AU Silver, RM
Parker, CB
Goldenberg, R
Reddy, UM
Dudley, DJ
Saade, GR
Hogue, CJR
Coustan, D
Varner, MW
Koch, MA
Conway, D
Bukowski, R
Pinar, H
Stoll, B
Moore, J
Willinger, M
AF Silver, Robert M.
Parker, Corette B.
Goldenberg, Robert
Reddy, Uma M.
Dudley, Donald J.
Saade, George R.
Hogue, Carol J. Rowland
Coustan, Donald
Varner, Michael W.
Koch, Matthew A.
Conway, Deborah
Bukowski, Radek
Pinar, Halit
Stoll, Barbara
Moore, Janet
Willinger, Marian
TI Bile acids in a multicenter, population-based case-control study of
stillbirth
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE bile acids; cholestasis; stillbirth
ID INTRAHEPATIC CHOLESTASIS; OBSTETRIC CHOLESTASIS; FETAL-DEATH; PREGNANCY;
MANAGEMENT; DIAGNOSIS; PATIENT
AB OBJECTIVE: We sought to compare bile acids in women with and without stillbirth in a population-based study.
STUDY DESIGN: The Stillbirth Collaborative Research Network conducted a multisite, population-based case-control study of stillbirth (fetal deaths >= 20 weeks). Maternal sera were obtained at the time of enrollment and frozen at -80 degrees C until assay for bile acids.
RESULTS: Assays were performed in 581 women with stillbirth and 1546 women with live births. Bile acid levels were slightly higher in women with stillbirth (geometric mean [95% confidence interval {CI}] - 3.2 [3.0-3.5]) compared to live births (2.9 [2.7-3.1], P=.0327). However, the difference was not significant after adjustment for baseline risk factors for stillbirth. The proportion of women with elevated levels (>= 10 or >= 40 mu mol/L) was similar in stillbirths and live births. Results were similar when the analysis was limited to subsets of stillbirths and live births. In women with stillbirths not associated with fetal anomalies or obstetric complications bile acid levels were higher than in women with term live births (geometric mean [95% CI] 3.4 [3.0-3.8] vs 2.9 [2.7-3.0], P=.0152, unadjusted; P=.06, adjusted). However, a similar proportion of women in both groups had levels >= 10 mu mol/L (10.7 vs 7.2%; odds ratio [OR], 1.54; 95% CI, 0.97-2.44; adjusted OR, 1.29; 95% CI, 0.78-2.15) and >= 40 mmol/L (1.7 vs 0.7%; OR, 2.58; 95% CI, 0.85-7.84; adjusted OR, 2.28; 95% CI, 0.79-6.56).
CONCLUSION: Our data do not support testing for bile acids in cases of stillbirth in the absence of clinical evidence of intrahepatic cholestasis of pregnancy.
C1 [Silver, Robert M.; Varner, Michael W.] Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA.
[Parker, Corette B.; Koch, Matthew A.; Moore, Janet] RTI Int, Res Triangle Pk, NC USA.
[Goldenberg, Robert] Columbia Univ, Dept Obstet & Gynecol, Coll Phys & Surg, New York, NY USA.
[Reddy, Uma M.; Willinger, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
[Dudley, Donald J.; Conway, Deborah] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Saade, George R.; Bukowski, Radek] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Hogue, Carol J. Rowland] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Stoll, Barbara] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Coustan, Donald] Brown Univ, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA.
[Pinar, Halit] Brown Univ, Alpert Med Sch, Dept Pathol, Providence, RI 02912 USA.
RP Silver, RM (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, 30 N 1900 East,Room 2B308, Salt Lake City, UT 84132 USA.
EM bsilver@hsc.utah.edu
RI Varner, Michael/K-9890-2013
OI Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Brown University [U10-HD045953]; Emory University
[U10-HD045925]; University of Texas Medical Branch at Galveston
[U10-HD045952]; University of Texas Health Sciences Center at San
Antonio [U10-HDO45955]; University of Utah Health Sciences Center, Salt
Lake City [U10-HD045944]; RTI International, Research Triangle Park
[U01-HD045954]
FX This work, including the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, and approval of the manuscript, was supported by grant funding
from the Eunice Kennedy Shriver National Institute of Child Health and
Human Development: U10-HD045953 Brown University; U10-HD045925 Emory
University; U10-HD045952 University of Texas Medical Branch at
Galveston; U10-HDO45955 University of Texas Health Sciences Center at
San Antonio; U10-HD045944 University of Utah Health Sciences Center,
Salt Lake City; and U01-HD045954 RTI International, Research Triangle
Park.
NR 25
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 MAY
PY 2014
VL 210
IS 5
AR 460.e1
DI 10.1016/j.ajog.2013.11.017
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AG6EF
UT WOS:000335510700021
PM 24215860
ER
PT J
AU Blaisdell, C
Noel, P
Kiley, J
AF Blaisdell, Carol
Noel, Patricia
Kiley, James
TI Primary Prevention of Chronic Lung Disease: A Role for Basic Science
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Editorial Material
C1 [Blaisdell, Carol; Noel, Patricia; Kiley, James] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA.
RP Blaisdell, C (reprint author), NHLBI, NIH, DHHS, Bldg 10, Bethesda, MD 20892 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 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD MAY
PY 2014
VL 50
IS 5
BP 841
EP 842
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA AG8DB
UT WOS:000335647900003
PM 24783954
ER
PT J
AU Cho, HY
Kleeberger, SR
AF Cho, Hye-Youn
Kleeberger, Steven R.
TI Noblesse Oblige: NRF2 Functions in the Airways
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE acute lung injury; tumorigenesis; transcription factor
ID ACUTE LUNG INJURY; NEONATAL MICE; INFLAMMATION; DEFICIENCY; PROTECTION;
RESOLUTION; HYPEROXIA; DELETION; IMPAIRS; FAMILY
AB The transcription factor, nuclear factor (NF), erythroid-derived 2-related factor 2 (NRF2), was discovered nearly 2 decades ago. Since then, over 4,000 papers have been published on NRF2 function in diverse biological systems, and it has been found to be a critical regulator of antioxidant and defense genes with antioxidant response elements in their promoters. NRF2 is particularly important in protecting cells and tissues under highly oxidative microenvironments, including the airways that interface with the external environment and are exposed to pollutants and other oxidant stressors. Using mice with targeted deletion of Nrf2, a protective role for this transcription factor has been determined in many model diseases, including acute lung injury, emphysema, allergy and asthma, pulmonary fibrosis, and respiratory syncytial virus disease. Recent studies have also found that murine Nrf2 is important in lung development and protection against neonatal lung injury. Moreover, functional polymorphisms in human NRF2 have been known to associate with disease severity, indicating a potentially important protective function. However, there is also a "dark side" to NRF2 function, as it has been found to enhance advanced stages of carcinogenesis in the lung and some other tissues. NRF2 inducers such as phytochemical isothyocyanates and synthetic triterpenoids, have been discovered and used in model systems of oxidant-induced lung diseases, and data suggest a potential for clinical interventions. Future investigations of NRF2 should yield further insight into its contribution to normal and pathophysiological conditions in the airways, and alternative treatment strategies to protect against oxidative respiratory disease.
C1 [Cho, Hye-Youn; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA.
EM cho2@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences; Department of
Health and Human Services
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences, Department of Health and Human Services.
NR 26
TC 5
Z9 5
U1 1
U2 12
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 MAY
PY 2014
VL 50
IS 5
BP 844
EP 847
DI 10.1165/rcmb.2014-0116PS
PG 4
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA AG8DB
UT WOS:000335647900005
PM 24783956
ER
PT J
AU Lazrak, A
Jurkuvenaite, A
Ness, EC
Zhang, SY
Woodworth, BA
Muhlebach, MS
Stober, VP
Lim, YP
Garantziotis, S
Matalon, S
AF Lazrak, Ahmed
Jurkuvenaite, Asta
Ness, Emily C.
Zhang, Shaoyan
Woodworth, Bradford A.
Muhlebach, Marianne S.
Stober, Vandy P.
Lim, Yow-Pin
Garantziotis, Stavros
Matalon, Sadis
TI Inter-alpha-Inhibitor Blocks Epithelial Sodium Channel Activation and
Decreases Nasal Potential Differences in Delta F508 Mice
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE alveolar type II cells; lung slices; human BAL; cystic fibrosis;
biotinylation
ID TRANSEPITHELIAL LIQUID TRANSPORT; HYALURONAN-BINDING PROTEIN; PIG
ALVEOLAR EPITHELIA; CYSTIC-FIBROSIS; TRYPSIN-INHIBITOR; NA+ CHANNEL;
CELL-SURFACE; IN-VITRO; RESPIRATORY EPITHELIA; LUNG-DISEASE
AB Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Inter-alpha-inhibitor (I alpha I), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High concentrations of I alpha I were detected in the bronchoalveolar lavage fluid (BALF) of children with CF and lower airway diseases. I alpha I decreased amiloride-sensitive (I-ENaC) but not cAMP-activated Cl- currents across confluent monolayers of rat ATII, and mouse nasal epithelial cells grew in primary culture by 45 and 25%, respectively. Changes in I-ENaC by I alpha I in ATII cells were accompanied by increased levels of uncleaved (immature) surface alpha-ENaC. I alpha I increased airway surface liquid depth overlying murine nasal epithelial cells to the same extent as amiloride, consistent with ENaC inhibition. Incubation of lung slices from C57BL/6, those lacking phenylalanine at position 508 (Delta F508), or CF transmembrane conductance regulator knockout mice with I alpha I for 3 hours decreased the open probability of their ENaC channels by 50%. Delta F508 mice had considerably higher levels the amiloride-sensitive fractions of ENaC nasal potential difference (ENaC-NPD) than wild-type littermates and only background levels of I alpha I in their BALF. A single intranasal instillation of I alpha I decreased their ENaC-NPD 24 hours later by 25%. In conclusion, we show that I alpha I is present in the BALF of children with CF, is an effective inhibitor of ENaC proteolysis, and decreases ENaC activity in lung epithelial cells of Delta F508 mice.
C1 [Lazrak, Ahmed; Jurkuvenaite, Asta; Ness, Emily C.; Matalon, Sadis] Univ Alabama Birmingham, Dept Anesthesiol, Birmingham, AL USA.
[Zhang, Shaoyan; Woodworth, Bradford A.] Univ Alabama Birmingham, Dept Surg, Div Otolaryngol, Birmingham, AL 35294 USA.
[Lazrak, Ahmed; Jurkuvenaite, Asta; Ness, Emily C.; Matalon, Sadis] Univ Alabama Birmingham, Dept Pulm Injury & Repair, Birmingham, AL USA.
[Zhang, Shaoyan; Woodworth, Bradford A.; Matalon, Sadis] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL USA.
[Muhlebach, Marianne S.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Stober, Vandy P.; Garantziotis, Stavros] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Lim, Yow-Pin] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Lim, Yow-Pin] ProThera Biol, East Providence, RI USA.
RP Matalon, S (reprint author), BMR 2 224,901 19th St South, Birmingham, AL 35205 USA.
EM sadis@uab.edu
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
FU CounterACT Program; National Institutes of Health Office of the
Director; National Institute of Neurological Disorders and Stroke
[5U01ES015676, 1R21ES02402701]; National Heart, Lung and Blood Institute
[5R01HL031197]; Flight Attendant's Medical Research Institute Young
Clinical Scientist Award [072218]; National Institutes of
Health/National Heart, Lung and Blood Institute [1K08HL107142-02];
Division of Intramural Research, National Institute of Environmental
Health Sciences, National Institutes of Health
FX This work was supported by the CounterACT Program; by National
Institutes of Health Office of the Director and the National Institute
of Neurological Disorders and Stroke grants 5U01ES015676 and
1R21ES02402701; by National Heart, Lung and Blood Institute grant
5R01HL031197 (S.M.); by the Flight Attendant's Medical Research
Institute Young Clinical Scientist Award (072218) and National
Institutes of Health/National Heart, Lung and Blood Institute grant
1K08HL107142-02 (B.A.W.); and by the Division of Intramural Research,
National Institute of Environmental Health Sciences, National Institutes
of Health (S.G.).
NR 62
TC 8
Z9 8
U1 1
U2 1
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 MAY
PY 2014
VL 50
IS 5
BP 953
EP 962
DI 10.1165/rcmb.2013-0215OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA AG8DB
UT WOS:000335647900018
PM 24303840
ER
PT J
AU Cantey, PT
Coyle, CM
Sorvillo, FJ
Wilkins, PP
Starr, MC
Nash, TE
AF Cantey, Paul T.
Coyle, Christina M.
Sorvillo, Frank J.
Wilkins, Patricia P.
Starr, Michelle C.
Nash, Theodore E.
TI Neglected Parasitic Infections in the United States: Cysticercosis
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID TAENIA-SOLIUM TAENIASIS; LOS-ANGELES-COUNTY; ORTHODOX JEWISH-COMMUNITY;
EXTRAPARENCHYMAL NEUROCYSTICERCOSIS; CLINICAL-MANIFESTATIONS; DIAGNOSIS;
DISEASE; SEROPREVALENCE; TAPEWORM; SEIZURES
AB Cysticercosis is a potentially fatal and preventable neglected parasitic infection caused by the larval form of Taenia solium. Patients with symptomatic disease usually have signs and symptoms of neurocysticercosis, which commonly manifest as seizures or increased intracranial pressure. Although there are many persons living in the United States who emigrated from highly disease-endemic countries and there are foci of autochthonous transmission of the parasite in the United States, little is known about burden and epidemiology of the disease in this country. In addition, despite advances in the diagnosis and management of neurocysticercosis, there remain many unanswered questions. Improving our understanding and management of neurocysticercosis in the United States will require improved surveillance or focused prospective studies in appropriate areas and allocation of resources towards answering some of the key questions discussed in this report.
C1 [Cantey, Paul T.; Wilkins, Patricia P.] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Atlanta, GA 30333 USA.
[Coyle, Christina M.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Starr, Michelle C.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Sorvillo, Frank J.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Nash, Theodore E.] NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Cantey, PT (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, 1600 Clifton Rd NE,Mailstop A-06, Atlanta, GA 30333 USA.
EM pcantey@cdc.gov; christina.coyle@einstein.yu.edu;
franksorvillo@yahoo.com; pwilkins@cdc.gov;
michelle.starr@seattlechildrens.org; tnash@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, U.S. National
Institutes of Health
FX This study was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, U.S. National
Institutes of Health.
NR 60
TC 18
Z9 18
U1 1
U2 10
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 MAY
PY 2014
VL 90
IS 5
BP 805
EP 809
DI 10.4269/ajtmh.13-0724
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AG8ZN
UT WOS:000335707600007
PM 24808248
ER
PT J
AU Sirugo, G
Predazzi, IM
Bartlett, J
Tacconelli, A
Walther, M
Williams, SM
AF Sirugo, Giorgio
Predazzi, Irene M.
Bartlett, Jacquelaine
Tacconelli, Alessandra
Walther, Michael
Williams, Scott M.
TI Short Report: G6PD A- Deficiency and Severe Malaria in The Gambia:
Heterozygote Advantage and Possible Homozygote Disadvantage
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY; NATURAL-SELECTION;
RESISTANCE; HETEROGENEITY; AFRICA; HEMIZYGOTES; POPULATION
AB Glucose-6-phosphate dehydrogenase (G6PD) deficiency is frequent in Africa, because it confers resistance to Plasmodium falciparum malaria; however, the nature of the protection and the genotypes associated with it have been controversial. In 1972, Bienzle and others described protection from malaria in West African females heterozygous for G6PD A-. They determined that G6PD A- heterozygotes had lower parasite counts than A- homozygotes, hemizygous males, and normal individuals. However, other studies have reached different conclusions about the protective genotypes. DNA samples from 135 children with severe malaria and 146 children with mild malaria from The Gambia were genotyped for the G6PD A- mutation that is most frequent among Gambians (G6PD 968 T->C); there was a marked deficiency of heterozygotes and an excess of homozygotes with severe malaria, producing a strong deviation from Hardy Weinberg equilibrium. Our results support the protective effect in G6PD A- heterozygous females and suggest that homozygotes might be more susceptible to severe malaria attacks.
C1 [Sirugo, Giorgio; Tacconelli, Alessandra] Osped San Pietro Fatebenefratelli, Ctr Ric, I-00189 Rome, Italy.
[Predazzi, Irene M.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA.
[Bartlett, Jacquelaine; Williams, Scott M.] Dartmouth Coll, Geisel Sch Med, Dept Genet, Hanover, NH 03755 USA.
[Walther, Michael] NIAID, NIH, Lab Malaria Immunol & Vaccinol, Rockville, MD USA.
MRC Labs, Banjul, Gambia.
RP Sirugo, G (reprint author), Osped San Pietro Fatebenefratelli, Ctr Ric, Via Cassia 600, I-00189 Rome, Italy.
EM sirugo.giorgio@fbfrm.it; irene.m.predazzi@vanderbilt.edu;
Jacquelaine.Bartlett@dartmouth.edu; alessandra.tacconelli@gmail.com;
michael.walther@nih.gov; Scott.Williams@dartmouth.edu
FU NIH [GM103534]
FX SMW was partially supported by NIH grant GM103534.
NR 16
TC 8
Z9 8
U1 0
U2 7
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 MAY
PY 2014
VL 90
IS 5
BP 856
EP 859
DI 10.4269/ajtmh.13-0622
PG 4
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AG8ZN
UT WOS:000335707600017
PM 24615128
ER
PT J
AU Uddin, T
Aktar, A
Xu, P
Johnson, RA
Rahman, MA
Leung, DT
Afrin, S
Akter, A
Alam, MM
Rahman, A
Chowdhury, F
Khan, AI
Bhuiyan, TR
Bufano, MK
Rashu, R
Yu, YN
Wu-Freeman, Y
Harris, JB
LaRocque, RC
Charles, RC
Kovac, P
Calderwood, SB
Ryan, ET
Qadri, F
AF Uddin, Taher
Aktar, Amena
Xu, Peng
Johnson, Russell A.
Rahman, M. Arifur
Leung, Daniel T.
Afrin, Sadia
Akter, Aklima
Alam, Mohammad Murshid
Rahman, Atiqur
Chowdhury, Fahima
Khan, Ashraful I.
Bhuiyan, Taufiqur Rahman
Bufano, Meagan K.
Rashu, Rasheduzzaman
Yu, Yanan
Wu-Freeman, Ying
Harris, Jason B.
LaRocque, Regina C.
Charles, Richelle C.
Kovac, Pavol
Calderwood, Stephen B.
Ryan, Edward T.
Qadri, Firdausi
TI Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of
Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral
Killed Cholera Vaccine and Comparison to Responses in Patients with
Cholera
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID MEMORY B-CELL; ANTIBODY-SECRETING CELL; INFECTION-DERIVED IMMUNITY;
WHOLE-CELL; STRUCTURAL-ANALYSIS; HOUSEHOLD CONTACTS; CONTROLLED-TRIAL;
CORE REGION; ANTIGEN; CHILDREN
AB Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae 01 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection.
C1 Icddr B, Ctr Vaccine Sci, Dhaka, Bangladesh.
[Uddin, Taher; Aktar, Amena; Johnson, Russell A.; Rahman, M. Arifur; Afrin, Sadia; Akter, Aklima; Alam, Mohammad Murshid; Chowdhury, Fahima; Khan, Ashraful I.; Rashu, Rasheduzzaman; Qadri, Firdausi] Icddr B, Immunol Lab, Dhaka, Bangladesh.
[Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
[Harris, Jason B.; LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Leung, Daniel T.; Bufano, Meagan K.; Rashu, Rasheduzzaman; Yu, Yanan; Wu-Freeman, Ying] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[LaRocque, Regina C.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Rahman, Atiqur] Univ Dhaka, Dept Biochem & Mol Biol, Dhaka, Bangladesh.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Qadri, F (reprint author), 68 Shaheed Tajuddin Ahmed Sharani, Dhaka 1212, Bangladesh.
EM taher_imm@icddrb.org; bio_amn015@yahoo.com; xup3@mail.nih.gov;
russell.a.johnson@gmail.com; marifur@icddrb.org; dleung@partners.org;
sadia_afrin89@yahoo.com; aklima17@gmail.com; shafiul@icddrb.org;
atique303@gmail.com; fchowdhury@icddrb.org; ashrafk@icddrb.org;
MBUFANO@partners.org; rashedimm@yahoo.co; YYVAUGHN@PARTNERS.ORG;
YWUFREEMAN@PARTNERS.ORG; jbharris@partners.org; RCLAROCQUE@PARTNERS.ORG;
RCCHARLES@PARTNERS.ORG; Kovac@maihnh.gov; SCALDERWOOD@PARTNERS.ORG;
ETRYAN@PARTNERS.ORG; fqadri@icddrb.org
RI Kovac, Pavol/B-8813-2008; Xu, Peng/K-7036-2012;
OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801
FU icddr,b; National Institutes of Health; NIDDK; National Institutes of
Health [U01 AI058935, R03 AI063079, U01 AI077883, AI106878, K08
AI089721, K08A1100923]; Fogarty International Center; Training Grant in
Vaccine Development and Public Health [TW005572]; Career Development
Awards [K01 TW07409, K01 TW07144]; Fogarty International Clinical
Research Scholars Award [R24 TW007988]; Swedish Sida
[INT-ICDDR,B-HN-01-AV]; Howard Hughes Medical Institute; American
Society for Tropical Medicine and Hygiene - Burroughs Wellcome Fund;
Thrasher Research Fund Early Career Award
FX This research was supported by the icddr,b, by the Intramural Research
Program of the National Institutes of Health, NIDDK, and extramural
grants from the National Institutes of Health, including the National
Institute of Allergy and Infectious Diseases (U01 AI058935 [S.B.C.,
E.T.R.], R03 AI063079 [F.Q.], U01 AI077883 and AI106878 [E.T.R.]), K08
AI089721 [R.C.C.], K08A1100923 [D.T.L.]) and the Fogarty International
Center, Training Grant in Vaccine Development and Public Health
(TW005572 [T.U., M.M.A., R.R., and F.Q.]), Career Development Awards
(K01 TW07409 [J.B.H.] and K01 TW07144 [R.C.L.], and a Fogarty
International Clinical Research Scholars Award (R24 TW007988 [T.U.,
R.A.J.]), as well as by Swedish Sida grant INT-ICDDR,B-HN-01-AV (F.Q.),
a Physician Scientist Early Career Award from the Howard Hughes Medical
Institute (R.C.L.), a Postdoctoral Fellowship in Tropical Infectious
Diseases from the American Society for Tropical Medicine and Hygiene -
Burroughs Wellcome Fund (D.T.L.), and a Thrasher Research Fund Early
Career Award (D.T.L.).
NR 49
TC 7
Z9 7
U1 1
U2 5
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 MAY
PY 2014
VL 90
IS 5
BP 873
EP 881
DI 10.4269/ajtmh.13-0498
PG 9
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AG8ZN
UT WOS:000335707600020
PM 24686738
ER
PT J
AU Fox, A
Whitehead, S
Anders, KL
Hoa, LNM
Mai, LQ
Thai, PQ
Yen, NT
Duong, TN
Thoang, DD
Farrar, J
Wertheim, H
Simmons, C
Hien, NT
Horby, P
AF Fox, Annette
Whitehead, Stephen
Anders, Katherine L.
Le Nguyen Minh Hoa
Le Quynh Mai
Pham Quang Thai
Nguyen Thu Yen
Tran Nhu Duong
Dang Dinh Thoang
Farrar, Jeremy
Wertheim, Heiman
Simmons, Cameron
Nguyen Tran Hien
Horby, Peter
TI Short Report: Investigation of Dengue and Japanese Encephalitis Virus
Transmission in Hanam, Viet Nam
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID RISK-FACTORS; INFECTION; MOSQUITOS; EPIDEMIOLOGY; SURVEILLANCE;
SEVERITY; THAILAND; VECTORS; COHORT
AB This study investigated whether a large dengue epidemic that struck Hanoi in 2009 also affected a nearby semirural area. Seroconversion (dengue virus-reactive immunoglobulin G enzyme-linked immunosorbent assay) was high during 2009 compared with 2008, but neutralization assays showed that it was caused by both dengue virus and Japanese encephalitis virus infections. The findings highlight the importance of continued Japanese encephalitis virus vaccination and dengue surveillance.
C1 Univ Oxford, Clin Res Unit, Oxford, England.
Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
NIAID, Bethesda, MD 20892 USA.
[Nguyen Tran Hien] Natl Inst Hyg & Epidemiol, Hanoi, Vietnam.
[Dang Dinh Thoang] Hanam Ctr Prevent Med, Hanam, Vietnam.
[Fox, Annette] Natl Hosp Trop Dis Viet Nam, Hanoi, Vietnam.
[Whitehead, Stephen] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
[Anders, Katherine L.] Univ Oxford, Clin Res Unit Viet Nam, Dengue Grp, Ho Chi Minh City, Vietnam.
[Anders, Katherine L.; Farrar, Jeremy; Simmons, Cameron] Univ Oxford, Clin Res Unit, Hosp Trop Dis, Ho Chi Minh City, Vietnam.
[Le Nguyen Minh Hoa; Wertheim, Heiman; Horby, Peter] Univ Oxford, Clin Res Unit Viet Nam, Natl Hosp Trop Dis, Hanoi, Vietnam.
[Le Quynh Mai] Natl Inst Hyg & Epidemiol Virol, Hanoi, Vietnam.
[Pham Quang Thai; Nguyen Thu Yen; Tran Nhu Duong] Natl Inst Hyg & Epidemiol Epidemiol, Hanoi, Vietnam.
[Horby, Peter] Univ Oxford, Clin Res Unit Trop Med, Hanoi, Vietnam.
RP Fox, A (reprint author), Natl Hosp Trop Dis Viet Nam, 78 Giai Phong Rd, Hanoi, Vietnam.
EM afox@pacific.net.au; swhitehead@niaid.nih.gov; kanders@oucru.org;
hoalnm@oucru.or; lom9@hotmail.com; phamquangthai@gmail.com;
yentc2004@gmail.com; trannhuduong@gmail.com; trannhuduong@gmail.com;
J.Farrar@wellcome.ac.uk; hwertheim@oucru.org; csimmons@oucru.org;
ngtrhien@yahoo.com; peter.horby@gmail.com
OI Simmons, Cameron P./0000-0002-9039-7392
FU Wellcome Trust United Kingdom [081613/Z/06/Z, 077078/Z/05/Z]; US
National Institute of Allergy and Infectious Diseases; European Union
[223498]
FX This work was supported by Wellcome Trust United Kingdom Grants
081613/Z/06/Z and 077078/Z/05/Z and in part, the Intramural Research
Program of the US National Institute of Allergy and Infectious Diseases.
A.F. was supported by the European Union FP7 project European Management
Platform for Emerging and Re-Emerging Infectious Disease Entities
(EMPERIE; no. 223498).
NR 20
TC 1
Z9 1
U1 0
U2 4
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 MAY
PY 2014
VL 90
IS 5
BP 892
EP 896
DI 10.4269/ajtmh.13-0077
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AG8ZN
UT WOS:000335707600022
PM 24615123
ER
PT J
AU Cross, RW
Waffa, B
Freeman, A
Riegel, C
Moses, LM
Bennett, A
Safronetz, D
Fischer, ER
Feldmann, H
Voss, TG
Bausch, DG
AF Cross, Robert W.
Waffa, Bradley
Freeman, Ashley
Riegel, Claudia
Moses, Lina M.
Bennett, Andrew
Safronetz, David
Fischer, Elizabeth R.
Feldmann, Heinz
Voss, Thomas G.
Bausch, Daniel G.
TI Old World Hantaviruses in Rodents in New Orleans, Louisiana
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID UNITED-STATES; HEMORRHAGIC-FEVER; RENAL SYNDROME; HANTAAN VIRUS; SEOUL
HANTAVIRUS; NORWAY RATS; BALTIMORE; INFECTION; MARYLAND; ANTIBODY
AB Seoul virus, an Old World hantavirus, is maintained in brown rats and causes a mild form of hemorrhagic fever with renal syndrome (HFRS) in humans. We captured rodents in New Orleans, Louisiana and tested them for the presence of Old World hantaviruses by reverse transcription polymerase chain reaction (RT-PCR) with sequencing, cell culture, and electron microscopy; 6 (3.4%) of 178 rodents captured all brown rats were positive for a Seoul virus variant previously coined Tchoupitoulas virus, which was noted in rodents in New Orleans in the 1980s. The finding of Tchoupitoulas virus in New Orleans over 25 years since its first discovery suggests stable endemicity in the city. Although the degree to which this virus causes human infection and disease remains unknown, repeated demonstration of Seoul virus in rodent populations, recent cases of laboratory-confirmed HFRS in some US cities, and a possible link with hypertensive renal disease warrant additional investigation in both rodents and humans.
C1 [Cross, Robert W.; Waffa, Bradley; Moses, Lina M.; Bennett, Andrew; Voss, Thomas G.; Bausch, Daniel G.] Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA.
[Freeman, Ashley; Riegel, Claudia] New Orleans Termite Mosquito & Rodent Control Boa, New Orleans, LA USA.
[Safronetz, David; Fischer, Elizabeth R.; Feldmann, Heinz] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
RP Cross, RW (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Dept Microbiol & Immunol, Room 5-324,301 Univ Blvd,Mail Route 10610, Galveston, TX 77555 USA.
EM rwcross@utmb.edu; bjwaffa@ncsu.edu; Anfree1005@yahoo.com;
criegel@cityofno.com; linammoses@gmail.com; Andrew.j.bennett@gmail.com;
safronetzd@niaid.nih.gov; efischer@niaid.nih.gov;
feldmannh@niaid.nih.gov; thomas.voss@sri.com; dbausch@tulane.edu
FU Tulane University Research Enhancement grant
FX Funding for this research was provided by a Tulane University Research
Enhancement grant.
NR 33
TC 2
Z9 2
U1 0
U2 4
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 MAY
PY 2014
VL 90
IS 5
BP 897
EP 901
DI 10.4269/ajtmh.13-0683
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AG8ZN
UT WOS:000335707600023
PM 24639295
ER
PT J
AU Andersen, SW
Trentham-Dietz, A
Gangnon, RE
Hampton, JM
Figueroa, JD
Skinner, HG
Engelman, CD
Klein, BE
Titus, LJ
Egan, KM
Newcomb, PA
AF Andersen, Shaneda Warren
Trentham-Dietz, Amy
Gangnon, Ronald E.
Hampton, John M.
Figueroa, Jonine D.
Skinner, Halcyon G.
Engelman, Corinne D.
Klein, Barbara E.
Titus, Linda J.
Egan, Kathleen M.
Newcomb, Polly A.
TI Reproductive windows, genetic loci, and breast cancer risk
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Breast neoplasms; Epidemiology; Menarche; Menopause; Genetic loci;
Histology
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; VARIANTS; 5P12;
POLYMORPHISMS; CONSORTIUM; MENARCHE; TRENDS; COHORT; WOMEN
AB Purpose: The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk.
Methods: We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample (N = 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models.
Results: For standardized age at first birth, the OR was 1.52 (CI, 1.36-1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 (RAD51B) appeared to modify this relationship (P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35-1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype.
Conclusions: Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Andersen, Shaneda Warren; Trentham-Dietz, Amy; Hampton, John M.; Newcomb, Polly A.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53726 USA.
[Andersen, Shaneda Warren; Trentham-Dietz, Amy; Gangnon, Ronald E.; Skinner, Halcyon G.; Engelman, Corinne D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53726 USA.
[Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Klein, Barbara E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
[Titus, Linda J.] Norris Cotton Canc Ctr, Geisel Sch Med Dartmouth, Lebanon, NH USA.
[Egan, Kathleen M.] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA.
[Egan, Kathleen M.] Res Inst, Tampa, FL USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
RP Andersen, SW (reprint author), Univ Wisconsin, Carbone Canc Ctr, 610 Walnut St,WARF Room 307, Madison, WI 53726 USA.
EM snandersen@uwalumni.com
FU National Institutes of Health [R01CA47147, R01CA47305, R01CA69664,
U10EY006594]; Department of Defense Breast Cancer Research Program
[W81XWH-11-1-0047]; Intramural Research Funds of the National Cancer
Institute, Department of Health and Human Services
FX The authors would like to thank the study staff and participants for all
of their individual contributions. This work was supported by grants
from the National Institutes of Health (grant numbers R01CA47147,
R01CA47305, R01CA69664, and U10EY006594), the Department of Defense
Breast Cancer Research Program (W81XWH-11-1-0047), and Intramural
Research Funds of the National Cancer Institute, Department of Health
and Human Services.
NR 27
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD MAY
PY 2014
VL 24
IS 5
BP 376
EP 382
DI 10.1016/j.annepidem.2014.02.007
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AG9BB
UT WOS:000335712500008
ER
PT J
AU Kaufman, SS
Green, KY
Korba, BE
AF Kaufman, Stuart S.
Green, Kim Y.
Korba, Brent E.
TI Treatment of norovirus infections: Moving antivirals from the bench to
the bedside
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Norovirus; Transplant; Antiviral; Immunocompromised; Drug treatment;
Diarrhea
ID STEM-CELL TRANSPLANTATION; DEPENDENT RNA-POLYMERASE; NORWALK
VIRUS-REPLICATION; UNITED-STATES; VIRAL GASTROENTERITIS; 3C-LIKE
PROTEASES; MONOCLONAL-ANTIBODIES; FAVIPIRAVIR T-705; MURINE NOROVIRUS;
INHIBITORS
AB Noroviruses (NV) are the most common cause of acute gastrointestinal illness in the United States and worldwide. The development of specific antiviral countermeasures has lagged behind that of other viral pathogens, primarily because norovirus disease has been perceived as brief and self-limiting and robust assays suitable for drug discovery have been lacking. The increasing recognition that NV illness can be life-threatening, especially in immunocompromised patients who often require prolonged hospitalization and intensive supportive care, has stimulated new research to develop an effective antiviral therapy. Here, we propose a path forward for evaluating drug therapy in norovirus-infected immunocompromised individuals, a population at high risk for serious and prolonged illness. The clinical and laboratory features of norovirus illness in immunocompromised patients are reviewed, and potential markers of drug efficacy are defined. We discuss the potential design of clinical trials in these patients and how an antiviral therapy that proves effective in immunocompromised patients might also be used in the setting of acute outbreaks, especially in confined settings such as nursing homes, to block the spread of infection and reduce the severity of illness. We conclude by reviewing the current status of approved and experimental compounds that might be evaluated in a hospital setting. (c) 2014 Elsevier B.V. All rights reserved.
C1 [Kaufman, Stuart S.] Georgetown Univ, Med Ctr, MedStar Georgetown Transplant Inst, Washington, DC 20007 USA.
[Kaufman, Stuart S.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA.
[Green, Kim Y.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Korba, Brent E.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA.
RP Korba, BE (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA.
EM korbabe@georgetown.edu
FU Intramural NIH HHS [Z99 AI999999]
NR 107
TC 27
Z9 27
U1 0
U2 19
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 MAY
PY 2014
VL 105
BP 80
EP 91
DI 10.1016/j.antiviral.2014.02.012
PG 12
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA AG7XC
UT WOS:000335631100013
PM 24583027
ER
PT J
AU Giannouli, CC
Chandris, P
Proia, RL
AF Giannouli, Christina C.
Chandris, Panagiotis
Proia, Richard L.
TI Visualizing S1P-directed cellular egress by intravital imaging
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Review
DE Sphingosine-1-phosphate; Sphingolipid; Signaling; Gradient; Receptor;
Two-photon microscopy
ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; SPHINGOSINE-1-PHOSPHATE TRANSPORTER
SPNS2; PROTEIN-COUPLED RECEPTOR; SPLENIC MARGINAL ZONE; LYMPHOCYTE
EGRESS; T-CELLS; FLUORESCENT PROTEINS; 2-PHOTON MICROSCOPY; IN-VIVO;
INTERACTION DYNAMICS
AB Sphingosine-1-phosphate (S1P) is a bioactive lipid that provides cellular signals through plasma membrane G protein-coupled receptors. The SW receptor signaling system has a fundamental and widespread function in licensing the exit and release of hematopoietically derived cells from various tissues into the circulation. Although the outlines of the mechanism have been established through genetic and pharmacologic perturbations, the temporal and spatial dynamics of the cellular events involved have been unclear. Recently, two-photon intravital imaging has been applied to living tissues to visualize the cellular movements and interactions that occur during egress processes. Here we discuss how some of these recent findings provide a clearer picture regarding SW receptor signaling in modulating cell egress into the circulation. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology. Published by Elsevier B.V.
C1 [Giannouli, Christina C.; Chandris, Panagiotis; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
EM christina.giannouli@nih.gov; Panagiotis.Chandris@nih.gov; proia@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 93
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD MAY
PY 2014
VL 1841
IS 5
SI SI
BP 738
EP 744
DI 10.1016/j.bbalip.2013.09.012
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AG8ZC
UT WOS:000335706400011
PM 24090699
ER
PT J
AU Outeda, P
Huso, DL
Fisher, SA
Halushka, MK
Kim, H
Qian, F
Germino, GG
Watnick, T
AF Outeda, Patricia
Huso, David L.
Fisher, Steven A.
Halushka, Marc K.
Kim, Hyunho
Qian, Feng
Germino, Gregory G.
Watnick, Terry
TI Polycystin Signaling Is Required for Directed Endothelial Cell Migration
and Lymphatic Development
SO CELL REPORTS
LA English
DT Article
ID KIDNEY-DISEASE; 2-HIT MODEL; IN-VIVO; VESSELS; PKD1; MICE; CYSTOGENESIS;
MUTATIONS; POLARITY; DEFECTS
AB Autosomal dominant polycystic kidney disease is a common form of inherited kidney disease that is caused by mutations in two genes, PKD1 (polycystin-1) and PKD2 (polycystin-2). Mice with germline deletion of either gene die in midgestation with a vascular phenotype that includes profound edema. Although an endothelial cell defect has been suspected, the basis of this phenotype remains poorly understood. Here, we demonstrate that edema in Pkd1- and Pkd2-null mice is likely to be caused by defects in lymphatic development. Pkd1 and Pkd2 mutant embryos exhibit reduced lymphatic vessel density and vascular branching along with aberrant migration of early lymphatic endothelial cell precursors. We used cell-based assays to confirm that PKD1- and PKD2-depleted endothelial cells have an intrinsic defect in directional migration that is associated with a failure to establish front-rear polarity. Our studies reveal a role for polycystin signaling in lymphatic development.
C1 [Outeda, Patricia; Kim, Hyunho; Qian, Feng; Watnick, Terry] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
[Huso, David L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
[Fisher, Steven A.] Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA.
[Halushka, Marc K.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Germino, Gregory G.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Watnick, T (reprint author), Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
EM twatnick@medicine.umaryland.edu
OI Halushka, Marc/0000-0002-7112-7389
FU NIH [R01DK076017, R01DK095036, R01HL65314, R01DK062199, R37DK48006];
NIDDK Intramural Program [1ZIADK075042]; Maryland Kidney Foundation;
National Kidney Foundation Postdoctoral Research Fellowship; American
Heart Association [13GRNT16420015]; NIDDK [P30DK090868]
FX We thank members of the Baltimore Polycystic Kidney Disease (PKD)
Research and Clinical Core Center for helpful discussions. This work was
supported by the NIH (R01DK076017 and R01DK095036 to T.W., R01HL65314 to
S.A.F., R01DK062199 to F.Q., and R37DK48006 to G.G.G.), the NIDDK
Intramural Program (1ZIADK075042 to G.G.G.), a Minigrant from the
Maryland Kidney Foundation and a National Kidney Foundation Postdoctoral
Research Fellowship to P.O., and the American Heart Association
(13GRNT16420015 to M.K.H.). These studies utilized reagents provided by
the Baltimore PKD Research and Clinical Core Center, sponsored by the
NIDDK (P30DK090868).
NR 32
TC 15
Z9 15
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD MAY
PY 2014
VL 7
IS 3
BP 634
EP 644
DI 10.1016/j.celrep.2014.03.064
PG 11
WC Cell Biology
SC Cell Biology
GA AG6WZ
UT WOS:000335560900005
PM 24767998
ER
PT J
AU Wang, L
Du, Y
Ward, JM
Shimbo, T
Lackford, B
Zheng, XF
Miao, YL
Zhou, BY
Han, L
Fargo, DC
Jothi, R
Williams, CJ
Wade, PA
Hu, G
AF Wang, Li
Du, Ying
Ward, James M.
Shimbo, Takashi
Lackford, Brad
Zheng, Xiaofeng
Miao, Yi-liang
Zhou, Bingying
Han, Leng
Fargo, David C.
Jothi, Raja
Williams, Carmen J.
Wade, Paul A.
Hu, Guang
TI INO80 Facilitates Pluripotency Gene Activation in Embryonic Stem Cell
Self-Renewal, Reprogramming, and Blastocyst Development
SO CELL STEM CELL
LA English
DT Article
ID CORE TRANSCRIPTIONAL NETWORK; CHROMATIN REMODELING COMPLEX; RNAI SCREEN;
GENOME; DIFFERENTIATION; EXPRESSION; IDENTITY; MEDIATOR; OCT4;
MECHANISMS
AB The master transcription factors play integral roles in the pluripotency transcription circuitry of embryonic stem cells (ESCs). How they selectively activate expression of the pluripotency network while simultaneously repressing genes involved in differentiation is not fully understood. Here, we define a requirement for the INO80 complex, a SWI/SNF family chromatin remodeler, in ESC self-renewal, somatic cell reprogramming, and blastocyst development. We show that Ino80, the chromatin remodeling ATPase, co-occupies pluripotency gene promoters with the master transcription factors, and its occupancy is dependent on OCT4 and WDR5. At the pluripotency genes, Ino80 maintains an open chromatin architecture and licenses recruitment of Mediator and RNA polymerase II for gene activation. Our data reveal an essential role for INO80 in the expression of the pluripotency network and illustrate the coordination among chromatin remodeler, transcription factor, and histone-modifying enzyme in the regulation of the pluripotent state.
C1 [Wang, Li; Shimbo, Takashi; Lackford, Brad; Zheng, Xiaofeng; Jothi, Raja; Wade, Paul A.; Hu, Guang] NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA.
[Du, Ying; Ward, James M.; Fargo, David C.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Miao, Yi-liang; Williams, Carmen J.] NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA.
[Zhou, Bingying] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Zhou, Bingying] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Han, Leng] Univ Texas Houston, Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
RP Wade, PA (reprint author), NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov; hug4@niehs.nih.gov
RI Jothi, Raja/G-3780-2015; Hu, Guang/E-7474-2016
OI Hu, Guang/0000-0003-0437-4723
FU NIH, National Institute of Environmental Health Sciences [Z01ES102745,
Z01ES101965, Z01ES102985, Z01ES102625]
FX We thank Drs. Trevor Archer and Karen Adelman for reading the
manuscript. This study was supported in part by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
Z01ES102745 (to G. H.), Z01ES101965 (to P. A. W.), Z01ES102985 (to
C.J.W.), and Z01ES102625 (to R.J.).
NR 55
TC 41
Z9 43
U1 3
U2 27
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD MAY 1
PY 2014
VL 14
IS 5
BP 575
EP 591
DI 10.1016/j.stem.2014.02.013
PG 17
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA AG8HR
UT WOS:000335659900008
PM 24792115
ER
PT J
AU Tate, JA
Snitz, BE
Alvarez, KA
Nahin, RL
Weissfeld, LA
Lopez, O
Angus, DC
Shah, F
Ives, DG
Fitzpatrick, AL
Williamson, JD
Arnold, AM
DeKosky, ST
Yende, S
AF Tate, Judith A.
Snitz, Beth E.
Alvarez, Karina A.
Nahin, Richard L.
Weissfeld, Lisa A.
Lopez, Oscar
Angus, Derek C.
Shah, Faraaz
Ives, Diane G.
Fitzpatrick, Annette L.
Williamson, Jeffrey D.
Arnold, Alice M.
DeKosky, Steven T.
Yende, Sachin
CA GEM Study Investigators
TI Infection Hospitalization Increases Risk of Dementia in the Elderly
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE older adults; dementia; pneumonia; infection
ID RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; LONG-TERM
MORTALITY; QUALITY-OF-LIFE; ALZHEIMERS-DISEASE; INFLAMMATORY MARKERS;
COGNITIVE FUNCTION; VASCULAR DEMENTIA; CLINICAL-CRITERIA; PROPENSITY
SCORE
AB Objectives:
Severe infections, often requiring ICU admission, have been associated with persistent cognitive dysfunction. Less severe infections are more common and whether they are associated with an increased risk of dementia is unclear. We determined the association of pneumonia hospitalization with risk of dementia in well-functioning older adults.
Design:
Secondary analysis of a randomized multicenter trial to determine the effect of Gingko biloba on incident dementia.
Setting:
Five academic medical centers in the United States.
Subjects:
Healthy community volunteers (n = 3,069) with a median follow-up of 6.1 years.
Interventions:
None.
Measurement and Main Results:
We identified pneumonia hospitalizations using International Classification of Diseases, 9th Edition-Coding Manual codes and validated them in a subset. Less than 3% of pneumonia cases necessitated ICU admission, mechanical ventilation, or vasopressor support. Dementia was adjudicated based on neuropsychological evaluation, neurological examination, and MRI. Two hundred twenty-one participants (7.2%) incurred at least one hospitalization with pneumonia (mean time to pneumonia = 3.5 yr). Of these, dementia was developed in 38 (17%) after pneumonia, with half of these cases occurring 2 years after the pneumonia hospitalization. Hospitalization with pneumonia was associated with increased risk of time to dementia diagnosis (unadjusted hazard ratio = 2.3; CI, 1.6-3.2; p < 0.0001). The association remained significant when adjusted for age, sex, race, study site, education, and baseline mini-mental status examination (hazard ratio = 1.9; CI, 1.4-2.8; p < 0.0001). Results were unchanged when additionally adjusted for smoking, hypertension, diabetes, heart disease, and preinfection functional status. Results were similar using propensity analysis where participants with pneumonia were matched to those without pneumonia based on age, probability of developing pneumonia, and similar trajectories of cognitive and physical function prior to pneumonia (adjusted prevalence rates, 91.7 vs 65 cases per 1,000 person-years; adjusted prevalence rate ratio = 1.6; CI, 1.06-2.7; p = 0.03). Sensitivity analyses showed that the higher risk also occurred among those hospitalized with other infections.
Conclusion:
Hospitalization with pneumonia is associated with increased risk of dementia.
C1 [Tate, Judith A.] Univ Pittsburgh, Sch Nursing, Dept Acute & Tertiary Care, Pittsburgh, PA 15261 USA.
[Snitz, Beth E.; Lopez, Oscar] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Alvarez, Karina A.; Weissfeld, Lisa A.] Univ Pittsburgh, Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA.
[Nahin, Richard L.] NIH, NCCAM, Bethesda, MD 20892 USA.
[Weissfeld, Lisa A.; Angus, Derek C.; Yende, Sachin] Univ Pittsburgh, Clin Res Invest & Syst Modeling Acute Illnes, Pittsburgh, PA USA.
[Angus, Derek C.; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA.
[Shah, Faraaz] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
[Ives, Diane G.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Fitzpatrick, Annette L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Williamson, Jeffrey D.] Wake Forest Sch Med, Sec Gerontol & Geriatr Med, Winston Salem, NC USA.
[Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[DeKosky, Steven T.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
RP Tate, JA (reprint author), Univ Pittsburgh, Sch Nursing, Dept Acute & Tertiary Care, Pittsburgh, PA 15261 USA.
EM jta100@pitt.edu
RI Tate, Judith/C-7447-2015; Angus, Derek/E-9671-2012;
OI Nahin, Richard/0000-0002-3682-4816
FU National Center for Complementary and Alternative Medicine [U01
AT000162]; Office of Dietary Supplements; National Institute on Aging;
National Heart, Lung, and Blood Institute; University of Pittsburgh
Alzheimer's Disease Research Center [P50AG05133]; Roena Kulynych Center
for Memory and Cognition Research; Wake Forest University School of
Medicine; National Institute of Neurological Disorders and Stroke;
National Institute of Mental Health [T32-MH19986]; National Institutes
of Health (NIH) [T-32 MH19986]; National Institute on Aging [NIA
5K23AG038479]; NIH; National Center for Complementary and Alternative
Medicine/NIH; Centers for Disease Control and Prevention (CDC); National
Institute of General Medical Sciences [K23GM083215]; [T-32 (MH19986)];
[NIA: P50 AG05133-27]
FX Gingko Effect on Memory study was supported by grant U01 AT000162 from
the National Center for Complementary and Alternative Medicine and the
Office of Dietary Supplements and National Institute on Aging; National
Heart, Lung, and Blood Institute; University of Pittsburgh Alzheimer's
Disease Research Center (P50AG05133); Roena Kulynych Center for Memory
and Cognition Research; Wake Forest University School of Medicine; and
National Institute of Neurological Disorders and Stroke.; Dr. Tate is
funded by T-32 (MH19986-principal investigator [PI] Reynolds). Dr.
Tate's institution received grant support from the National Institute of
Mental Health (T32-MH19986-PI Reynolds). Dr. Tate received support for
article research from the National Institutes of Health (NIH) (T-32
MH19986-PI Reynolds). Dr. Snitz is supported by National Institute on
Aging (NIA 5K23AG038479). Dr. Snitz's institution received grant support
from the NIH. Dr. Snitz received support for article research from the
NIH. Dr. Nahin is employed by the NIH. Dr. Lopez consulted for Grifols,
Lilly, and Baxter. Dr. Lopez's institution received grant support (NIA:
P50 AG05133-27).; Dr. Ives' institution received grant support and
support for travel from National Center for Complementary and
Alternative Medicine/NIH. Dr. Ives is employed by the University of
Pittsburgh and received support for article research from the NIH. Dr.
Fitzpatrick and her institution received grant support from the NIH and
Centers for Disease Control and Prevention (CDC). Dr. Fitzpatrick
received support for article research from the NIH and CDC. Dr.
Williamson's institution received grant support and support for travel
from the NIH. Dr. Williamson received support for article research from
the NIH. Dr. Arnold and her institution received grant support from the
NIH. Dr. Arnold received support for travel and support for article
research from the NIH. Dr. DeKosky's institution received grant support
from the NIH, support for travel from the NIH, and the active Gingko
Extract and the placebo tablets for the original Gingko Effect on Memory
trial from Schwabe Pharamaceuticals. Dr. DeKosky received support for
article research from the NIH. Dr. Yende's institution received grant
support from the NIH. Dr. Yende received support for article research
from the NIH and National Institute of General Medical Sciences
(K23GM083215). The remaining authors have disclosed that they do not
have any potential conflicts of interest.
NR 50
TC 6
Z9 6
U1 1
U2 5
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 MAY
PY 2014
VL 42
IS 5
BP 1037
EP 1046
DI 10.1097/CCM.0000000000000123
PG 10
WC Critical Care Medicine
SC General & Internal Medicine
GA AG4IU
UT WOS:000335383900018
PM 24368344
ER
PT J
AU Nydahl, P
Ruhl, AP
Bartoszek, G
Dubb, R
Filipovic, S
Flohr, HJ
Kaltwasser, A
Mende, H
Rothaug, O
Schuchhardt, D
Schwabbauer, N
Needham, DM
AF Nydahl, Peter
Ruhl, A. Parker
Bartoszek, Gabriele
Dubb, Rolf
Filipovic, Silke
Flohr, Hans-Juergen
Kaltwasser, Arnold
Mende, Hendrik
Rothaug, Oliver
Schuchhardt, Danny
Schwabbauer, Norbert
Needham, Dale M.
TI Early Mobilization of Mechanically Ventilated Patients: A 1-Day
Point-Prevalence Study in Germany*
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE intensive care units; prevalence; early mobilization; surveys; physical
therapists; mechanical ventilation
ID INTENSIVE-CARE-UNIT; QUALITY IMPROVEMENT PROJECT; ACUTE
RESPIRATORY-FAILURE; PHYSICAL REHABILITATION; OCCUPATIONAL-THERAPY;
FUNCTIONAL RECOVERY; INTERVENTION; FEASIBILITY; EXERCISE; SEDATION
AB Objectives:
There is growing evidence to support early mobilization of adult mechanically ventilated patients in ICUs. However, there is little knowledge regarding early mobilization in routine ICU practice. Hence, the interdisciplinary German ICU Network for Early Mobilization undertook a 1-day point-prevalence survey across Germany.
Design:
One-day point-prevalence study.
Setting:
One hundred sixteen ICUs in Germany in 2011.
Patients:
All adult mechanically ventilated patients.
Interventions:
None.
Measurements and Main Results:
For a 24-hour period, data were abstracted on hospital and ICU characteristics, the level of patient mobilization and associated barriers, and complications occurring during mobilization. One hundred sixteen participating ICUs provided data for 783 patients. Overall, 185 patients (24%) were mobilized out of bed (i.e., sitting on the edge of the bed or higher level of mobilization). Among patients with an endotracheal tube, tracheostomy, and noninvasive ventilation, 8%, 39%, and 53% were mobilized out of bed, respectively (p < 0.001 for difference between three groups). The most common perceived barriers to mobilizing patients out of bed were cardiovascular instability (17%) and deep sedation (15%). Mobilization out of bed versus remaining in bed was not associated with a higher frequency of complications, with no falls or extubations occurring in those mobilized out of bed.
Conclusions:
In this 1-day point-prevalence study conducted across Germany, only 24% of all mechanically ventilated patients and only 8% of patients with an endotracheal tube were mobilized out of bed as part of routine care. Addressing modifiable barriers for mobilization, such as deep sedation, will be important to increase mobilization in German ICUs.
C1 [Nydahl, Peter] Univ Hosp Schleswig Holstein, Nursing Res Nursing & Patient Serv, Kiel, Germany.
[Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA.
[Ruhl, A. Parker] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bartoszek, Gabriele] Univ Witten Herdecke, Fac Nursing Sci, Witten, Germany.
[Dubb, Rolf] Klinikum Stuttgart, Katharinenhosp, Dept Anaesthesiol & Operat Intens Care Med, Stuttgart, Germany.
[Filipovic, Silke] Univ Hosp Giessen & Marburg GmbH, Dept Physiotherapy, Marburg, Germany.
[Flohr, Hans-Juergen] Work & Life Educ Assoc, Gottingen, Germany.
[Kaltwasser, Arnold] Dist Hosp Reutlingen, Dept Continuing Educ Crit Care Nursing, Reutlingen, Germany.
[Mende, Hendrik] Klin Eichert, Alb Fils Kliniken GmbH, Dept Anaesthesiol & Intens Care Med, Goppingen, Germany.
[Rothaug, Oliver] Univ Hosp Gottingen, Dept Anaesthesiol Emergency & Intens Care Med, Gottingen, Germany.
[Schuchhardt, Danny] Zent Klin Bad Berka, Dept Anaesthesia & Intens Care Med, Bad Berka, Germany.
[Schwabbauer, Norbert] Univ Hosp Tubingen, Dept Med, Tubingen, Germany.
[Needham, Dale M.] Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA.
RP Nydahl, P (reprint author), Univ Hosp Schleswig Holstein, Nursing Res Nursing & Patient Serv, Campus Kiel, Kiel, Germany.
EM peter.nydahl@uksh.de
FU German Interdisciplinary Association of Critical Care Medicine; National
Institutes of Health
FX Mr. Nydahl lectured for Hill-Rom and received support for article
research from The German Interdisciplinary Association of Critical Care
Medicine, which had no role in designing and conducting the study, data
collection, management, analysis, and interpretation of the data; or the
preparation, review, or approval of the article. Mr. Kaltwasser
consulted for Kimberly-Clark Health Care (KCC) and Hollister; lectured
for Hollister, KCC, and Smith Medical; received support for article
preparation from Hollister; and received support for article research
from German Interdisciplinary Association of Critical Care Medicine Mr.
Schuchhardt lectured for and received support for the development of
educational presentations from the company providing material for
management of chronic wounds. Dr. Needham's institution received grant
support (National Institutes of Health peer-reviewed grants). The
remaining authors have disclosed that they do not have any potential
conflicts of interest.
NR 42
TC 50
Z9 56
U1 3
U2 31
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 MAY
PY 2014
VL 42
IS 5
BP 1178
EP 1186
DI 10.1097/CCM.0000000000000149
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA AG4IU
UT WOS:000335383900034
PM 24351373
ER
PT J
AU Pastores, SM
Martin, GS
Baumann, MH
Curtis, JR
Farmer, JC
Fessler, HE
Gupta, R
Hill, NS
Hyzy, RC
Kvetan, V
MacGregor, DA
O'Grady, NP
Ognibene, FP
Rubenfeld, GD
Sessler, CN
Siegal, E
Simpson, SQ
Spevetz, A
Ward, NS
Zimmerman, JL
AF Pastores, Stephen M.
Martin, Greg S.
Baumann, Michael H.
Curtis, J. Randall
Farmer, J. Christopher
Fessler, Henry E.
Gupta, Rakesh
Hill, Nicholas S.
Hyzy, Robert C.
Kvetan, Vladimir
MacGregor, Drew A.
O'Grady, Naomi P.
Ognibene, Frederick P.
Rubenfeld, Gordon D.
Sessler, Curtis N.
Siegal, Eric
Simpson, Steven Q.
Spevetz, Antoinette
Ward, Nicholas S.
Zimmerman, Janice L.
CA CCSC Task Force Critical Care Educ
TI Training Internists to Meet Critical Care Needs in the United States: A
Consensus Statement from the Critical Care Societies Collaborative
(CCSC)*
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE fellowship education; workforce; requirements; internal medicine;
critical care medicine; training
ID MEDICAL-EDUCATION; BED NUMBERS; BRONCHOSCOPY; RECOMMENDATIONS;
GUIDELINES; SIMULATION; WORKFORCE; OUTCOMES; COSTS; ICU
AB Objectives:
Multiple training pathways are recognized by the Accreditation Council for Graduate Medical Education (ACGME) for internal medicine (IM) physicians to certify in critical care medicine (CCM) via the American Board of Internal Medicine. While each involves 1 year of clinical fellowship training in CCM, substantive differences in training requirements exist among the various pathways. The Critical Care Societies Collaborative convened a task force to review these CCM pathways and to provide recommendations for unified and coordinated training requirements for IM-based physicians.
Participants:
A group of CCM professionals certified in pulmonary-CCM and/or IM-CCM from ACGME-accredited training programs who have expertise in education, administration, research, and clinical practice.
Data Sources and Synthesis:
Relevant published literature was accessed through a MEDLINE search and references provided by all task force members. Material published by the ACGME, American Board of Internal Medicine, and other specialty organizations was also reviewed. Collaboratively and iteratively, the task force reached consensus using a roundtable meeting, electronic mail, and conference calls.
Main Results:
Internal medicine-CCM-based fellowships have disparate program requirements compared to other internal medicine subspecialties and adult CCM fellowships. Differences between IM-CCM and pulmonary-CCM programs include the ratio of key clinical faculty to fellows and a requirement to perform 50 therapeutic bronchoscopies. Competency-based training was considered uniformly desirable for all CCM training pathways.
Conclusions:
The task force concluded that requesting competency-based training and minimizing variations in the requirements for IM-based CCM fellowship programs will facilitate effective CCM training for both programs and trainees.
C1 [Pastores, Stephen M.] Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care Med, New York, NY 10021 USA.
[Martin, Greg S.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care, Atlanta, GA USA.
[Baumann, Michael H.] Univ Mississippi, Med Ctr, Div Pulm Crit Care & Sleep Med, Jackson, MS 39216 USA.
[Curtis, J. Randall] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA.
[Farmer, J. Christopher] Mayo Clin Arizona, Phoenix, AZ USA.
[Fessler, Henry E.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Gupta, Rakesh] Orlando Hlth, Orlando Reg Med Ctr, Orlando, FL USA.
[Hill, Nicholas S.] Tufts Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA USA.
Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Kvetan, Vladimir] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care,Crit Care Med Montefiore Med Ctr, Bronx, NY 10467 USA.
[Kvetan, Vladimir] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Crit Care, Bronx, NY 10467 USA.
[MacGregor, Drew A.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[O'Grady, Naomi P.; Ognibene, Frederick P.] NIH, Bethesda, MD 20892 USA.
[Rubenfeld, Gordon D.] Sunnybrook Hlth Sci Ctr, Trauma Emergency & Crit Care Program, Toronto, ON M4N 3M5, Canada.
[Sessler, Curtis N.] Virginia Commonwealth Univ Hlth Syst, Ctr Adult Crit Care, Med Coll Virginia Hosp & Phys, Richmond, VA USA.
[Siegal, Eric] Aurora Hlth Care, Madison, WI USA.
[Siegal, Eric] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Simpson, Steven Q.] Univ Kansas, Div Pulm & Crit Care, Kansas City, KS USA.
[Spevetz, Antoinette] Rowan Univ, Cooper Univ Hosp, Cooper Med Sch, Camden, NJ USA.
[Ward, Nicholas S.] Brown Univ, Alpert Med Sch, Div Pulm Crit Care & Sleep Med, Providence, RI 02912 USA.
[Zimmerman, Janice L.] Weill Cornell Med Coll, Houston, TX USA.
[Zimmerman, Janice L.] Houston Methodist Hosp, Houston, TX USA.
RP Pastores, SM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Anesthesiol & Crit Care Med, 1275 York Ave, New York, NY 10021 USA.
OI Pastores, Stephen/0000-0002-8850-7062; Martin, Greg/0000-0002-9684-7593
FU Spectral Diagnostics; Bayer Healthcare; NIH; FDA; Baxter Healthcare;
Abbott Laboratories; ACCP Board of Regents; PCORI; CCM; Kansas City Area
Life Sciences Foundation
FX Dr. Pastores' institution received grant support from Spectral
Diagnostics (Dr. Pastores is principal investigator at MSKCC for a
septic shock clinical trial) and Bayer Healthcare (Dr. Pastores is
principal investigator at MSKCC for a gram-negative pneumonia clinical
trial). Dr. Martin served as an advisory board member for Cumberland
Pharmaceuticals and Pulsion Medical Systems and his institution received
grant support from NIH, FDA, Baxter Healthcare, and Abbott Laboratories.
Dr. Baumann served as board member for ACCP Board of Regents, is
employed by the University of Mississippi Medical Center, received
support for the development of educational presentations (various post
graduate courses and other products for ACCP and/or ATS), and received
support for travel (paid as part of ACCP Board of Regents). Dr. Curtis'
institution received grant support from NIH and PCORI. Dr. Fessler
received support for development of educational presentations from
Oakstone Medical Publishers (Payment for editorial services for a
monthly journal review digest in CCM) and received support for travel
from American Thoracic Society (Travel expenses to attend committee
meetings) and the Association of Pulmonary and Critical Care Medicine
Program Directors (Travel expenses to attend committee meetings or to
represent the Association at professional society meetings). Dr. O'Grady
served as a board member for ABIM and is a government employee. Dr.
Ognibene is an employee of the U.S. government and has no copyright
authority. Dr. Simpson received support for travel from the Surviving
Sepsis Campaign (Planning committee for national sepsis collaborative)
and other: IMPRESS Study (North American Co-Chair for the International
Multicenter Prevalence Study on Sepsis; no honorarium). His institution
received grant support from Kansas City Area Life Sciences Foundation
(Grant for sepsis quality improvement work in Kansas City). The
remaining authors have disclosed that they do not have any potential
conflicts of interest.
NR 27
TC 2
Z9 2
U1 1
U2 5
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 MAY
PY 2014
VL 42
IS 5
BP 1272
EP 1279
DI 10.1097/CCM.0000000000000250
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA AG4IU
UT WOS:000335383900044
ER
PT J
AU Ghosh, M
Brancato, SJ
Agarwal, PK
Apolo, AB
AF Ghosh, Monalisa
Brancato, Sam J.
Agarwal, Piyush K.
Apolo, Andrea B.
TI Targeted therapies in urothelial carcinoma
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE epidermal growth factor receptor family; targeted therapy; tyrosine
kinase inhibitors; urothelial carcinoma; vascular endothelial growth
factor
ID INVASIVE BLADDER-CANCER; PHASE-II TRIAL; TRANSITIONAL-CELL CARCINOMA;
ENDOTHELIAL GROWTH-FACTOR; DOSE-ESCALATION; ONCOLOGY-GROUP; OPEN-LABEL;
NEOADJUVANT CHEMOTHERAPY; SYSTEMIC CHEMOTHERAPY; CABOZANTINIB XL184
AB Purpose of reviewGreater understanding of the biology and genetics of urothelial carcinoma is helping to identify and define the role of molecules and pathways appropriate for novel-targeted therapies. Here, we review the targeted therapies that have been reported or are in ongoing urothelial carcinoma clinical trials, and highlight molecular targets characterized in preclinical and clinical studies.Recent findingsTrials in nonmuscle-invasive bladder cancer are evaluating the role of immunotherapy and agents targeting vascular endothelial growth factor (VEGF) or fibroblast growth factor receptor-3. In muscle-invasive bladder cancer, neoadjuvant studies have focused on combining VEGF agents with chemotherapy; adjuvant studies are testing vaccines and agents targeting the human epidermal growth factor receptor 2, p53, and Hsp27. In the first-line treatment of metastatic urothelial carcinoma, tubulin, cytotoxic T-lymphocyte antigen 4, Hsp27, and p53 are novel targets in clinical trials. The majority of targeted agents studied in urothelial carcinoma are in the second-line setting; new targets include CD105, polo-like kinase-1, phosphatidylinositide 3-kinases (PI3K), transforming growth factor receptor/activin receptor-like kinase , estrogen receptor, and the hepatocyte growth factor receptor (HGFR or MET).SummaryDevelopment of targeted therapies for urothelial carcinoma is still in early stages, consequently there have been no major therapeutic advances to date. However, greater understanding of urothelial carcinoma and solid tumor biology has resulted in a proliferation of clinical trials that could lead to significant advances in treatment strategies.
C1 [Ghosh, Monalisa; Apolo, Andrea B.] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Brancato, Sam J.; Agarwal, Piyush K.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Apolo, AB (reprint author), 10 Ctr Dr,Rm 12N226,MSC 1906, Bethesda, MD 20892 USA.
EM andrea.apolo@nih.gov
RI Brancato, Sam/K-3266-2014;
OI Brancato, Sam/0000-0002-3760-5818; Agarwal, Piyush/0000-0002-6042-6834
NR 92
TC 26
Z9 26
U1 0
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD MAY
PY 2014
VL 26
IS 3
BP 305
EP 320
DI 10.1097/CCO.0000000000000064
PG 16
WC Oncology
SC Oncology
GA AF9IP
UT WOS:000335028900010
PM 24685646
ER
PT J
AU Su, D
Stamatakis, L
Singer, EA
Srinivasan, R
AF Su, Daniel
Stamatakis, Lambros
Singer, Eric A.
Srinivasan, Ramaprasad
TI Renal cell carcinoma: molecular biology and targeted therapy
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
DE immunotherapy; renal cell carcinoma; targeted therapy
ID PHASE-III TRIAL; HIGH-DOSE INTERLEUKIN-2; INTERFERON-ALPHA; ADVANCED
CANCER; SUNITINIB; EVEROLIMUS; SORAFENIB; ANTIBODY; SAFETY; TEMSIROLIMUS
AB Purpose of reviewRenal cell carcinoma (RCC) continues to be the subject of vigorous clinical and translational investigation. Advances in systemic targeted therapies, new molecular pathways and immunotherapy approaches will be discussed.Recent findingsAgents targeting the vascular endothelial growth factor (VEGF) and/or the mammalian target of rapamycin (mTOR) pathways continue to be the mainstay for treating metastatic RCC (mRCC). Although enhanced target specificity has improved the toxicity profile associated with newer VEGF-pathway antagonists, durable complete responses remain the exception. Identification of novel pathways/agents, as well as the optimal sequencing and combination of existing targeted agents, remain areas of active study. In addition, emerging data from early clinical trials have reinvigorated interest in immunomodulatory agents.SummaryThe therapeutic armamentarium available to genitourinary oncologists continues to grow, but much work remains to be done to fully realize the potential of pathway-specific targeted strategies and immune-based approaches for mRCC.
C1 [Su, Daniel; Stamatakis, Lambros; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Singer, Eric A.] Rutgers Canc Inst New Jersey, Sect Urol Oncol, New Brunswick, NJ USA.
[Singer, Eric A.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA.
RP Srinivasan, R (reprint author), NCI, Mol Canc Sect, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr,CRC2-5950, Bethesda, MD 20892 USA.
EM ramasrin@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, Maryland, USA; National Cancer Institute
[P30CA072720]
FX This research was funded in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research, Bethesda, Maryland, USA.; This work was also supported
by a grant from the National Cancer Institute (P30CA072720).
NR 50
TC 24
Z9 25
U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8746
EI 1531-703X
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD MAY
PY 2014
VL 26
IS 3
BP 321
EP 327
DI 10.1097/CCO.0000000000000069
PG 7
WC Oncology
SC Oncology
GA AF9IP
UT WOS:000335028900011
PM 24675233
ER
PT J
AU Sanjuan, PM
Rice, SL
Witkiewitz, K
Mandler, RN
Crandall, C
Bogenschutz, MP
AF Sanjuan, Pilar M.
Rice, Samara L.
Witkiewitz, Katie
Mandler, Raul N.
Crandall, Cameron
Bogenschutz, Michael P.
TI Alcohol, tobacco, and drug use among emergency department patients
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Emergency department; Alcohol; Substance abuse; Tobacco; Addiction;
Negative binomial model
ID ABUSE TREATMENT NEED; BRIEF INTERVENTION; SUBSTANCE USE; PRIMARY-CARE;
UNITED-STATES; SERVICES UTILIZATION; GENERAL-POPULATION; PROBLEM
DRINKING; SCREENING-TEST; USE DISORDERS
AB Background: The prevalence of alcohol, tobacco, and other drug (ATOD) use among emergency department (ED) patients is high and many of these patients have unrecognized and unmet substance use treatment needs. Identification of patients in the ED with problem substance use is not routine at this time.
Methods: We examined screening data, including standardized measures of ATOD use (HSI, AUDIT-C, DAST-10), from 14,866 ED patients in six hospitals across the United States. We expected younger age, male gender, higher triage acuity, and other substance use severity (ATOD) to be associated both with use versus abstinence and with severity of each substance use type. We used negative binomial hurdle models to examine the association between covariates and (1) substance use versus abstinence (logistic submodel) and with (2) severity among those who used substances (count submodel).
Results: Rates of use and problem use in our sample were similar to or higher than other ED samples. Younger patients and males were more likely to use ATOD, but the association of age and gender with severity varied across substances. Triage level was a poor predictor of substance use severity. Alcohol, tobacco, and drug use were significantly associated with using other substances and severity of other substance use.
Conclusion: Better understanding of the demographic correlates of ATOD use and severity and the patterns of comorbidity among classes of substance can inform the design of optimal screening and brief intervention procedures addressing ATOD use among ED patients. Tobacco may be an especially useful predictor. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Sanjuan, Pilar M.; Rice, Samara L.; Witkiewitz, Katie; Bogenschutz, Michael P.] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA.
[Rice, Samara L.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14203 USA.
[Mandler, Raul N.] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA.
[Crandall, Cameron] Univ New Mexico, Hlth Sci Ctr, Dept Emergency Med, Albuquerque, NM 87131 USA.
[Bogenschutz, Michael P.] Univ New Mexico, Dept Psychiat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
RP Sanjuan, PM (reprint author), Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, 2650 Yale Blvd,MSC11-6280, Albuquerque, NM 87106 USA.
EM psanjuan@unm.edu
OI Bogenschutz, Michael/0000-0003-4530-3470
FU NIAAA NIH HHS [L30 AA019906, T32 AA018108]; NIDA NIH HHS [U10 DA013732,
K24 DA022412, L30 DA025498, U10 DA013035, U10 DA013714, U10 DA013720,
U10 DA015831, U10 DA015833, U10 DA020024, U10 DA020036]
NR 41
TC 7
Z9 7
U1 2
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD MAY 1
PY 2014
VL 138
BP 32
EP 38
DI 10.1016/j.drugalcdep.2014.01.025
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA AG7SN
UT WOS:000335618800005
PM 24594289
ER
PT J
AU Tomei, S
Wang, E
Delogu, LG
Marincola, FM
Bedognetti, D
AF Tomei, Sara
Wang, Ena
Delogu, Lucia Gemma
Marincola, Francesco M.
Bedognetti, Davide
TI Non-BRAF-targeted therapy, immunotherapy, and combination therapy for
melanoma
SO EXPERT OPINION ON BIOLOGICAL THERAPY
LA English
DT Review
DE adoptive T-cell transfer; combination therapy; immunotherapy; melanoma;
targeted therapy
ID PHASE-II TRIAL; TUMOR-INFILTRATING LYMPHOCYTES; DOSE RECOMBINANT
INTERLEUKIN-2; GASTROINTESTINAL STROMAL TUMOR; UNTREATED METASTATIC
MELANOMA; CANCER IMMUNE RESPONSIVENESS; CYTOLYTIC T-LYMPHOCYTES; TERT
PROMOTER MUTATIONS; ADOPTIVE CELL THERAPY; STAGE IV MELANOMA
AB Introduction: Melanoma is an aggressive disease characterized by a complex etiology. The discovery of key driving mutations (primarily BRAF mutations) led to the development of specific molecular inhibitors providing clinical benefit.
Areas covered: Although BRAF-specific drugs have perhaps yielded the best results in melanoma-targeted therapy, there still remain several limitations, mostly due to the emergence of resistance and the lack of efficacy in patients without BRAF mutation. Novel drugs are currently being tested in clinical trials and showed encouraging results. Such drugs can specifically target molecular pathways aberrantly activated or repressed during melanoma development (targeted therapy) or act in a way to enhance the host immune system to fight cancer (immunotherapy). Here we provide a detailed overview of the current clinical strategies, which lay beyond BRAF-targeted therapy, spanning from molecular-targeted therapy to immunotherapy and to combination therapy.
Expert opinion: Major advances in our understanding of the mechanisms behind melanoma development have led to the implementation of novel therapeutic drugs. Unfortunately, tools allowing prediction of responsiveness to a given treatment are not available yet. The increasing availability of high-throughput technologies will allow the elucidation of molecular mechanisms underlying responsiveness to cancer therapy and unveil an increased number of potential therapeutic targets.
C1 [Tomei, Sara; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Tomei, Sara; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide] Trans NIH Ctr Human Immunol CHI, Dept Transfus Med, IDIS, Bethesda, MD 20892 USA.
[Tomei, Sara] Weill Cornell Med Coll Qatar, Dept Med Genet, Doha, Qatar.
[Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar.
[Delogu, Lucia Gemma] Univ Sassari, Dipartimento Chim & Farm, I-07100 Sassari, Italy.
RP Tomei, S (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM sat2024@qatar-med.cornell.edu; bedognettid@cc.nih.gov
OI Bedognetti, Davide/0000-0002-5857-773X
NR 216
TC 11
Z9 11
U1 0
U2 16
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1471-2598
EI 1744-7682
J9 EXPERT OPIN BIOL TH
JI Expert Opin. Biol. Ther.
PD MAY
PY 2014
VL 14
IS 5
BP 663
EP 686
DI 10.1517/14712598.2014.890586
PG 24
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA AG5AC
UT WOS:000335430500009
PM 24625306
ER
PT J
AU Takasawa, K
Kashimada, K
Pelosi, E
Takagi, M
Morio, T
Asahara, H
Schlessinger, D
Mizutani, S
Koopman, P
AF Takasawa, Kei
Kashimada, Kenichi
Pelosi, Emanuele
Takagi, Masatoshi
Morio, Tomohiro
Asahara, Hiroshi
Schlessinger, David
Mizutani, Shuki
Koopman, Peter
TI FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1
during ovarian development in mice
SO FASEB JOURNAL
LA English
DT Article
DE sex determination; reproduction; LHX9
ID STEROIDOGENIC FACTOR-I; SEX DETERMINATION; NUCLEAR RECEPTOR; GONADAL
DEVELOPMENT; FOLLICLE DEVELOPMENT; GENE-EXPRESSION; GRANULOSA-CELLS;
MOUSE; FACTOR-1; PROMOTER
AB Steroidogenic factor 1 (SF1; Ad4BP/NR5A1) plays key roles in gonadal development. Initially, the Sf1 gene is expressed in mouse fetal gonads of both sexes, but later is up-regulated in testes and down-regulated in ovaries. While Sf1 expression is activated and maintained by Wilms tumor 1 (WT1) and LIM homeobox 9 (LHX9), the mechanism of sex-specific regulation remains unclear. We hypothesized that Sf1 is repressed by the transcription factor Forkhead box L2 (FOXL2) during ovarian development. In an in vitro system (TM3 cells), up-regulation of Sf1 by the WT1 splice variant WT1-KTS was antagonized by FOXL2, as determined by quantitative RT-PCR. Using reporter assays, we localized the Sf1 proximal promoter region involved in this antagonism to a 674-bp interval. A conserved FOXL2 binding site was identified in this interval by in vitro chromatin immunoprecipitation. Introducing mutations into this site abolished negative regulation by FOXL2 in reporter assays. Finally, in Foxl2-null mice, Sf1 expression was increased 2-fold relative to wild-type XX fetal gonads. Our results support the hypothesis that FOXL2 negatively regulates Sf1 expression by antagonizing WT1-KTS during early ovarian development in mice.Takasawa, K., Kashimada, K., Pelosi, E., Takagi, M., Morio, T., Asahara, H., Schlessinger, D., Mizutani, S., Koopman, P. FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice.
C1 [Takasawa, Kei; Kashimada, Kenichi; Takagi, Masatoshi; Morio, Tomohiro; Mizutani, Shuki] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138510, Japan.
[Asahara, Hiroshi] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Syst BioMed, Bunkyo Ku, Tokyo 1138510, Japan.
[Pelosi, Emanuele; Schlessinger, David] NIA, Intramural Res Program, Genet Lab, US Natl Inst Hlth Biomed Res Ctr, Baltimore, MD 21224 USA.
[Koopman, Peter] Univ Queensland, Inst Mol Biosci, Div Mol Genet & Dev, Brisbane, Qld, Australia.
RP Kashimada, K (reprint author), Tokyo Med & Dent Univ, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo 1138510, Japan.
EM kkashimada.ped@tmd.ac.jp
RI Koopman, Peter /C-9416-2009;
OI Koopman, Peter /0000-0001-6939-0914; Pelosi,
Emanuele/0000-0003-1890-9821; Takasawa, Kei/0000-0001-6947-4034;
Kashimada, Kenichi/0000-0003-2505-5932
FU Intramural Research Program of the U.S. National Institutes of Health,
National Institute on Aging; Ministry of Education, Culture, Sports,
Science, and Technology (MEXT) [23249071]; Japan Society for the
Promotion of Science (JSPS) KAKENHI grant [24115707]; Japan Science and
Technology Agency (JST) Core Research for Evolutionary Science and
Technology (CREST) [24591503]
FX The authors thank Dagmar Wilhelm (Monash University, Melbourne, VIC,
Australia) for critical reading of the manuscript and Atsushi Kubo
(Tokyo Medical and Dental University) for technical support. This
research was supported, in part, by the Intramural Research Program of
the U.S. National Institutes of Health, National Institute on Aging, for
E.P. and D.S.; Ministry of Education, Culture, Sports, Science, and
Technology (MEXT) Grants-in-Aid for Scientific Research (KAKENHI) grant
23249071, Japan Society for the Promotion of Science (JSPS) KAKENHI
grant 24115707, and Japan Science and Technology Agency (JST) Core
Research for Evolutionary Science and Technology (CREST), for H.A.; and
KAKENHI (C) grant 24591503, for K.K.
NR 40
TC 14
Z9 15
U1 0
U2 10
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD MAY
PY 2014
VL 28
IS 5
BP 2020
EP 2028
DI 10.1096/fj.13-246108
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA AG3RA
UT WOS:000335336000007
PM 24451388
ER
PT J
AU Devine, K
Stillman, RJ
DeCherney, AH
AF Devine, Kate
Stillman, Robert J.
DeCherney, Alan H.
TI The Affordable Care Act: early implications for fertility medicine
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
C1 [Devine, Kate; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA.
[Stillman, Robert J.] Shady Grove Fertil Ctr, Rockville, MD USA.
RP Devine, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 HD999999]
NR 5
TC 4
Z9 4
U1 0
U2 1
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 MAY
PY 2014
VL 101
IS 5
BP 1224
EP 1227
DI 10.1016/j.fertnstert.2014.01.024
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AG6BX
UT WOS:000335504600011
PM 24582184
ER
PT J
AU Louis, GMB
Sundaram, R
Sweeney, AM
Schisterman, EF
Maisog, J
Kannan, K
AF Louis, Germaine M. Buck
Sundaram, Rajeshwari
Sweeney, Anne M.
Schisterman, Enrique F.
Maisog, Jose
Kannan, Kurunthachalam
TI Urinary bisphenol A, phthalates, and couple fecundity: the Longitudinal
Investigation of Fertility and the Environment (LIFE) Study
SO FERTILITY AND STERILITY
LA English
DT Article
DE Bisphenol A; endocrine disrupting chemicals; fecundity; phthalates;
reproduction
ID ENDOCRINE-DISRUPTING CHEMICALS; IN-VITRO FERTILIZATION; REPRODUCTIVE
FUNCTION; HUMAN SEMEN; EXPOSURE; HEALTH; WOMEN; INFERTILITY;
METABOLITES; PREGNANCY
AB Objective: To assess the relationship between environmental chemicals and couple fecundity or time to pregnancy (TTP).
Design: Prospective cohort.
Setting: Communities of targeted populations with reported exposure.
Patient(s): 501 couples recruited upon discontinuing contraception to become pregnant, 2005-2009.
Intervention(s): None.
Main Outcome Measure(s): Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) estimated for each partner's chemical concentrations adjusted for age, body mass index, cotinine, creatinine, and research site while accounting for time off contraception.
Result(s): Couples completed interviews and anthropometric assessments and provided the urine specimens for quantification of bisphenol A (BPA) and 14 phthalate metabolites, which were measured using high-performance liquid chromatography with electrospray triple-quadrupole mass spectrometer. Women recorded menstruation and pregnancy test results in daily journals. Couples were evaluated until a positive human-chorionic gonadotropin pregnancy test or 12 cycles without pregnancy. Neither female nor male BPA concentration was associated with TTP (FOR 0.98; 95% CI, 0.86, 1.13 and FOR 1.04; 95% CI, 0.91, 1.18, respectively). Men's urinary concentrations of monomethyl, mono-n-butyl, and monobenzyl phthalates were associated with a longer TTP (FOR 0.80; 95% CI, 0.70, 0.93; FOR 0.82, 95% CI, 0.70, 0.97; and FOR 0.77, 95% CI, 0.65 0.92, respectively).
Conclusion(s): Select male but not female phthalate exposures were associated with an approximately 20% reduction in fecundity, underscoring the importance of assessing both partners' exposure to minimize erroneous conclusions. (C) 2014 by American Society for Reproductive Medicine.
C1 [Louis, Germaine M. Buck; Sundaram, Rajeshwari; Schisterman, Enrique F.; Maisog, Jose] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
[Sweeney, Anne M.] Texas A&M Rural Sch Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA.
[Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Div Environm Hlth Sci, Albany, NY USA.
[Kannan, Kurunthachalam] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12222 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
OI Sundaram, Rajeshwari/0000-0002-6918-5002; Schisterman,
Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490
FU National Institutes of Health, Intramural Research Program, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358, HHSN27500001]
FX Funded by the National Institutes of Health, Intramural Research
Program, Eunice Kennedy Shriver National Institute of Child Health and
Human Development (contracts N01-HD-3-3355; N01-HD-3-3356;
NOH-HD-3-3358; HHSN27500001).
NR 63
TC 35
Z9 35
U1 4
U2 50
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 MAY
PY 2014
VL 101
IS 5
BP 1359
EP 1366
DI 10.1016/j.fertnstert.2014.01.022
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AG6BX
UT WOS:000335504600038
ER
PT J
AU Whitcomb, BW
Mumford, SL
Perkins, NJ
Wactawski-Wende, J
Bertone-Johnson, ER
Lynch, KE
Schisterman, EF
AF Whitcomb, Brian W.
Mumford, Sunni L.
Perkins, Neil J.
Wactawski-Wende, Jean
Bertone-Johnson, Elizabeth R.
Lynch, Kristine E.
Schisterman, Enrique F.
TI Urinary cytokine and chemokine profiles across the menstrual cycle in
healthy reproductive-aged women
SO FERTILITY AND STERILITY
LA English
DT Article
DE Chemokines; cytokines; immunology; inflammation; menstrual cycle
ID COLONY-STIMULATING FACTOR; MARGINAL STRUCTURAL MODELS; HUMAN
ENDOMETRIUM; MULTIPLE IMPUTATION; PERIPHERAL-BLOOD; FERTILE WOMEN;
CELLS; IMPLANTATION; EXPRESSION; OVULATION
AB Objective: To assess the utility of urinary cytokines for monitoring reproductive function by considering detection, variation across the menstrual cycle, and relations with hormones.
Design: Longitudinal cohort study.
Setting: Academic institution.
Patient(s): Healthy, reproductive-aged women with self-reported regular menstrual cycles and at least one observed ovulatory cycle (n = 248).
Intervention(s): None.
Main Outcome Measure(s): Urinary cytokines measured by 30-plex immunoassays in 3,550 biospecimens, and nested random-effects analysis of variance (ANOVA) and marginal structural models used to evaluate variability and relations with hormones.
Result(s): For 24 of 30 evaluated factors, detectable levels were observed in at least 50% of urine samples. Interleukin-6 (IL-6), IL-8, IL-10, IL-15, granulocyte colony stimulating factor (G-CSF), hepatocyte growth factor (HGF), interferon-alpha (IFN-alpha), and RANTES (regulated upon activation normal T-cell expressed and secreted) levels varied significantly across the menstrual cycle. The proinflammatory factors IL-1 beta, IL-6, IL-8, and HGF were 1.5-3 times higher during menses than the late follicular phase. In marginal structural models, IL-1 beta, IL-6, IL-8 were associated with lower estradiol and progesterone concentrations.
Conclusion(s): Variability during the menstrual cycle and correlations with reproductive hormone levels support a role of cytokines in the menstrual cycle; however, because of the limited variability for most cytokines considered, the utility of urine as a matrix for assessment of inflammation in menstrual cycle function appears limited for clinical purposes. (C) 2014 by American Society for Reproductive Medicine.
C1 [Whitcomb, Brian W.; Bertone-Johnson, Elizabeth R.; Lynch, Kristine E.] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Mumford, Sunni L.; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Whitcomb, BW (reprint author), Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, 715 N Pleasant St, Amherst, MA 01003 USA.
EM bwhitcomb@schoolph.umass.edu
OI Perkins, Neil/0000-0002-6802-4733; Schisterman,
Enrique/0000-0003-3757-641X
FU National Institutes of Health, Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) [HHSN275200403394C]
FX Funded by the National Institutes of Health, Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD), contract HHSN275200403394C to the University
at Buffalo.
NR 48
TC 7
Z9 7
U1 4
U2 14
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 MAY
PY 2014
VL 101
IS 5
BP 1383
EP U39
DI 10.1016/j.fertnstert.2014.01.027
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA AG6BX
UT WOS:000335504600041
PM 24581581
ER
PT J
AU Valente, AJ
Irimpen, AM
Siebenlist, U
Chandrasekar, B
AF Valente, Anthony J.
Irimpen, Anand M.
Siebenlist, Ulrich
Chandrasekar, Bysani
TI OxLDL induces endothelial dysfunction and death via TRAF3IP2: Inhibition
by HDL3 and AMPK activators
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Atherosclerosis; Oxidative stress; NADPH oxidases; Endothelial
dysfunction; Free radicals
ID LOW-DENSITY-LIPOPROTEIN; PROTEIN-KINASE; AIRWAY INFLAMMATION; CELL
APOPTOSIS; UP-REGULATION; OXIDIZED LDL; CIKS ACT1; OX-LDL; OXIDATION;
RECEPTOR
AB Oxidized low-density lipoprotein (oxLDL) induces endothelial cell death through the activation of NF-kappa B and AP-1 pathways. TRAF3IP2 is a redox-sensitive cytoplasmic adapter protein and an upstream regulator of IKK/NF-kappa B and JNK/AP-1. Here we show that oxLDL-induced death in human primary coronary artery endothelial cells (ECs) was markedly attenuated by the knockdown of TRAF3IP2 or the lectin-like oxLDL receptor I (LOX-1). Further, oxLDL induced Nox2/superoxide-dependent TRAF3IP2 expression, IKK/p65 and JNK/c-Jun activation, and LOX-I upregulation, suggesting a reinforcing mechanism. Similarly, the lysolipids present in oxLDL (16:0-LPC and 18:0-LPC) and minimally modified LDL also upregulated TRAF3IP2 expression. Notably, whereas native HDL3 reversed oxLDL-induced TRAF3IP2 expression and cell death, 15-lipoxygenase-modified HDL3 potentiated its proapoptotic effects. The activators of the AMPK/Akt pathway, adiponectin, AICAR, and metformin, attenuated superoxide generation, TRAF3IP2 expression, and oxLDL/TRAF3IP2-mediated EC death. Further, both HDL3 and adiponectin reversed oxLDL/TRAF3IP2-dependent monocyte adhesion to endothelial cells in vitro. Importantly, TRAF3IP2 gene deletion and the AMPK activators reversed oxLDL-induced impaired vasorelaxation ex vivo. These results indicate that oxLDL-induced endothelial cell death and dysfunction are mediated via TRAF3IP2 and that native HDL3 and the AMPK activators inhibit this response. Targeting TRAF3IP2 could potentially inhibit progression of atherosclerotic vascular diseases. (c) 2014 Elsevier Inc. All rights reserved.
C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Irimpen, Anand M.; Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA.
[Irimpen, Anand M.; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Siebenlist, Ulrich] NIAID, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL-48, New Orleans, LA 70112 USA.
EM bchandra@tulane.edu
FU Department of Veterans Affairs Research Career Scientist award; VA
Office of Research and Development Biomedical Laboratory Research and
Development Service Award [1I01BX000246]; NIH/NHLBI [HL-86787]
FX B.C. is the recipient of a Department of Veterans Affairs Research
Career Scientist award and is supported by VA Office of Research and
Development Biomedical Laboratory Research and Development Service Award
1I01BX000246 and NIH/NHLBI Grant HL-86787. U.S. is supported by the
Intramural Research Program of the NIH/NIAID. The contents of this
report do not represent the views of the Department of Veterans Affairs
or the United States government.
NR 41
TC 15
Z9 18
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD MAY
PY 2014
VL 70
BP 117
EP 128
DI 10.1016/j.freeradbiomed.2014.02.014
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA AG5VP
UT WOS:000335487100012
PM 24561578
ER
PT J
AU Wang, GJ
Tomasi, D
Volkow, ND
Wang, R
Telang, F
Caparelli, EC
Dunayevich, E
AF Wang, G-J
Tomasi, D.
Volkow, N. D.
Wang, R.
Telang, F.
Caparelli, E. C.
Dunayevich, E.
TI Effect of combined naltrexone and bupropion therapy on the brain's
reactivity to food cues
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE fMRI; naltrexone; bupropion
ID NEURONAL RESPONSE; OBESE INDIVIDUALS; PREFRONTAL CORTEX; VENTRAL
STRIATUM; EATING BEHAVIOR; ACTIVATION; HUMANS; HIPPOCAMPUS; CIRCUITRY;
STIMULI
AB OBJECTIVE: The significant weight loss observed with combination naltrexone-sustained release (SR) 32mg and bupropion SR 360mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment.
METHODS: Forty women (31.1 +/- 8.1 years; body mass index: 32.5 +/- 3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (> 100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (similar to 14 h) were assessed before and after treatment.
RESULTS: The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05).
CONCLUSIONS: Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.
C1 [Wang, G-J; Wang, R.] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA.
[Wang, G-J] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA.
[Tomasi, D.; Volkow, N. D.; Telang, F.] NIAAA, Neuroimaging Lab, Intramural Program, Upton, NY USA.
[Volkow, N. D.] NIDA, Off Director, Bethesda, MD 20892 USA.
[Caparelli, E. C.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Dunayevich, E.] Amgen Inc, Newbury Pk, CA USA.
RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Biosci, POB 5000,30 Bell Ave,Bldg 490, Upton, NY 11973 USA.
EM gjwang@bnl.gov
RI Tomasi, Dardo/J-2127-2015
FU Orexigen Therapeutics Inc.; Intramural Research Program of the National
Institute on Alcoholism and Alcohol Abuse [Z01AA000550]
FX We thank Karen Apelskog-Torres for study protocol preparation, Millard
Jayne for subject recruitment, Barbara Hubbard and Pauline Carter for
patient care and Orexigen Therapeutics for scientific review of the
manuscript. The functional MR study was carried out at Brookhaven
National Laboratory with support from Orexigen Therapeutics Inc. (GJW)
and in part from Intramural Research Program of the National Institute
on Alcoholism and Alcohol Abuse, Z01AA000550 (NDV, FT, MJ).
NR 46
TC 14
Z9 14
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
EI 1476-5497
J9 INT J OBESITY
JI Int. J. Obes.
PD MAY
PY 2014
VL 38
IS 5
BP 682
EP 688
DI 10.1038/ijo.2013.145
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AG5FQ
UT WOS:000335445300010
PM 23924756
ER
PT J
AU Zhang, Y
Yu, XM
Ichikawa, M
Lyons, JJ
Datta, S
Lamborn, IT
Jing, H
Kim, ES
Biancalana, M
Wolfe, LA
DiMaggio, T
Matthews, HF
Kranick, SM
Stone, KD
Holland, SM
Reich, DS
Hughes, JD
Mehmet, H
McElwee, J
Freeman, AF
Freeze, HH
Su, HC
Milner, JD
AF Zhang, Yu
Yu, Xiaomin
Ichikawa, Mie
Lyons, Jonathan J.
Datta, Shrimati
Lamborn, Ian T.
Jing, Huie
Kim, Emily S.
Biancalana, Matthew
Wolfe, Lynne A.
DiMaggio, Thomas
Matthews, Helen F.
Kranick, Sarah M.
Stone, Kelly D.
Holland, Steven M.
Reich, Daniel S.
Hughes, Jason D.
Mehmet, Huseyin
McElwee, Joshua
Freeman, Alexandra F.
Freeze, Hudson H.
Su, Helen C.
Milner, Joshua D.
TI Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link
glycosylation defects to atopy, immune deficiency, autoimmunity, and
neurocognitive impairment
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Atopy; immune deficiency; hyper-IgE; neurocognitive impairment;
phosphoglucomutase 3; glycosylation; allergy; autoimmunity
ID HYPER-IGE SYNDROME; CONGENITAL DISORDERS; NUCLEOTIDE SUGARS; STAT3
MUTATIONS; O-GLCNACYLATION; JOBS-SYNDROME; DOCK8; MYOCLONUS; CHILDREN;
HEALTHY
AB Background: Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy.
Objective: We sought to define a genetic syndrome of severe atopy, increased serum IgE levels, immune deficiency, autoimmunity, and motor and neurocognitive impairment.
Methods: Eight patients from 2 families with similar syndromic features were studied. Thorough clinical evaluations, including brain magnetic resonance imaging and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, anti