FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Jang, JC
Chen, G
Wang, SH
Barnes, MA
Chung, JI
Camberis, M
Le Gros, G
Cooper, PJ
Steel, C
Nutman, TB
Lazar, MA
Nair, MG
AF Jang, Jessica C.
Chen, Gang
Wang, Spencer H.
Barnes, Mark A.
Chung, Josiah I.
Camberis, Mali
Le Gros, Graham
Cooper, Philip J.
Steel, Cathy
Nutman, Thomas B.
Lazar, Mitchell A.
Nair, Meera G.
TI Macrophage-Derived Human Resistin Is Induced in Multiple Helminth
Infections and Promotes Inflammatory Monocytes and Increased Parasite
Burden
SO PLOS PATHOGENS
LA English
DT Article
ID TOLL-LIKE RECEPTOR; INDUCED INTESTINAL INFLAMMATION;
SMOOTH-MUSCLE-CELLS; NEMATODE INFECTION; T-CELL; INSULIN-RESISTANCE;
TYPE-2 IMMUNITY; UP-REGULATION; IFN-GAMMA; ACTIVATION
AB Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg(+)). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg(-) 2 mice, hRetnTg(+) mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology.
C1 [Jang, Jessica C.; Chen, Gang; Wang, Spencer H.; Barnes, Mark A.; Chung, Josiah I.; Nair, Meera G.] Univ Calif Riverside, Div Biomed Sci, Sch Med, Riverside, CA 92521 USA.
[Camberis, Mali; Le Gros, Graham] Malaghan Inst Med Res, Wellington, New Zealand.
[Cooper, Philip J.] Lab Invest FEPIS, Quininde, Ecuador.
[Cooper, Philip J.] Pontificia Univ Catolica Ecuador, Ctr Invest Enfermedades Infecciosas, Quito, Ecuador.
[Cooper, Philip J.] St Georges Univ London, London, England.
[Steel, Cathy; Nutman, Thomas B.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Lazar, Mitchell A.] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
RP Nair, MG (reprint author), Univ Calif Riverside, Div Biomed Sci, Sch Med, Riverside, CA 92521 USA.
EM meera.nair@ucr.edu
RI Le Gros, Graham/C-6725-2011
FU NIH [1R01AI091759-01A1, P01DK49210, 1S10OD016290-01A1, MRI-1429826,
1S10RR028934-01]; Division of Intramural Research (DIR) of the National
Institute of Allergy and Infectious Diseases; UCR School of Medicine
initial complement and Academic Senate grant; Health Research Council of
New Zealand; Wellcome Trust [088862/Z/09/Z]
FX These studies were supported by the NIH (1R01AI091759-01A1 to MGN;
P01DK49210 to MAL), by the Division of Intramural Research (DIR) of the
National Institute of Allergy and Infectious Diseases (to CS and TBN),
UCR School of Medicine initial complement and Academic Senate grant to
MGN, the Health Research Council of New Zealand (to GLG) and the
Wellcome Trust (088862/Z/09/Z to PJC). The UCR NextGen sequencing and
bioinformatics core (IIGB) are supported by NIH 1S10OD016290-01A1,
MRI-1429826 and NIH 1S10RR028934-01. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 58
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Z9 9
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 JAN
PY 2015
VL 11
IS 1
AR e1004579
DI 10.1371/journal.ppat.1004579
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CA7OF
UT WOS:000349106100016
PM 25568944
ER
PT J
AU Pitzer, VE
Viboud, C
Alonso, WJ
Wilcox, T
Metcalf, CJ
Steiner, CA
Haynes, AK
Grenfell, BT
AF Pitzer, Virginia E.
Viboud, Cecile
Alonso, Wladimir J.
Wilcox, Tanya
Metcalf, C. Jessica
Steiner, Claudia A.
Haynes, Amber K.
Grenfell, Bryan T.
TI Environmental Drivers of the Spatiotemporal Dynamics of Respiratory
Syncytial Virus in the United States
SO PLOS PATHOGENS
LA English
DT Article
ID YOUNG-CHILDREN; NATIONAL-SURVEILLANCE; MEASLES EPIDEMICS; GROUP-B;
GROUP-A; TRANSMISSION DYNAMICS; SPATIAL HIERARCHIES;
INFECTIOUS-DISEASES; TRACT INFECTIONS; KILIFI DISTRICT
AB Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime in temperate countries including the United States, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV. In the United States, RSV activity is highly spatially structured, with seasonal peaks beginning in Florida in November through December and ending in the upper Midwest in February-March, and prolonged disease activity in the southeastern US. Using data on both age-specific hospitalizations and laboratory reports of RSV in the US, and employing a combination of statistical and mechanistic epidemic modeling, we examined the association between environmental variables and state-specific measures of RSV seasonality. Temperature, vapor pressure, precipitation, and potential evapotranspiration (PET) were significantly associated with the timing of RSV activity across states in univariate exploratory analyses. The amplitude and timing of seasonality in the transmission rate was significantly correlated with seasonal fluctuations in PET, and negatively correlated with mean vapor pressure, minimum temperature, and precipitation. States with low mean vapor pressure and the largest seasonal variation in PET tended to experience biennial patterns of RSV activity, with alternating years of "early-big" and "ate-small" epidemics. Our model for the transmission dynamics of RSV was able to replicate these biennial transitions at higher amplitudes of seasonality in the transmission rate. This successfully connects environmental drivers to the epidemic dynamics of RSV; however, it does not fully explain why RSV activity begins in Florida, one of the warmest states, when RSV is a winter-seasonal pathogen. Understanding and predicting the seasonality of RSV is essential in determining the optimal timing of immunoprophylaxis.
C1 [Pitzer, Virginia E.] Yale Univ, Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
[Pitzer, Virginia E.; Viboud, Cecile; Alonso, Wladimir J.; Wilcox, Tanya; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Metcalf, C. Jessica] Univ Oxford, Dept Zool, Oxford, England.
[Metcalf, C. Jessica; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Steiner, Claudia A.] US Dept HHS, Healthcare Cost & Utilizat Project, Ctr Delivery Org & Markets, Agcy Healthcare Res & Qual, Rockville, MD USA.
[Haynes, Amber K.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Pitzer, VE (reprint author), Yale Univ, Yale Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
EM virginia.pitzer@yale.edu
OI Pitzer, Virginia/0000-0003-1015-2289
FU Bill & Melinda Gates Foundation (Vaccine Modeling Initiative); Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science & Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health
FX This work was supported by the Bill & Melinda Gates Foundation (Vaccine
Modeling Initiative; https://vaccinemodeling.org/) and the Research and
Policy for Infectious Disease Dynamics (RAPIDD) program of the Science &
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health
(http://www.fic.nih.gov/about/staff/pages/epidemiology-population.aspx)
(VEP, CJM, and BTG). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 71
TC 14
Z9 14
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JAN
PY 2015
VL 11
IS 1
AR e1004591
DI 10.1371/journal.ppat.1004591
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CA7OF
UT WOS:000349106100023
PM 25569275
ER
PT J
AU Zong, XF
Hu, ML
Li, ZC
Cao, HB
Chen, XG
Tang, JS
AF Zong, Xiaofen
Hu, Maolin
Li, Zongchang
Cao, Hongbao
Chen, Xiaogang
Tang, Jinsong
TI DNA methylation in schizophrenia: progress and challenges
SO SCIENCE BULLETIN
LA English
DT Review
DE Schizophrenia; Epigenetics; DNA methylation; Reelin;
Catechol-O-methyltransferase
ID PERIPHERAL-BLOOD CELLS; DE-NOVO METHYLATION; MB-COMT PROMOTER; BIPOLAR
DISORDER; PSYCHIATRIC-DISORDERS; EPIGENETIC REGULATION; PLASMA
HOMOCYSTEINE; PREFRONTAL CORTEX; LEUKOCYTE DNA; GENE PROMOTER
AB Schizophrenia is a heterogeneous psychiatric disorder broadly accepted being caused by genetic and environmental factors. Although conventional genetic studies have identified some candidate genes for schizophrenia, low odds ratios and penetrance, and a lack of reproducibility have limited their explanatory power. Despite the major efforts made toward identifying environmental factors in schizophrenia, methodological limitations and inconsistent findings of epidemiological reports have obstructed attempts to identify exogenous causal factors. Epigenetic mechanisms, mediating between environment and genes, have recently been proposed to play an important role in the pathogenesis of schizophrenia. DNA methylation is the most stable and well-characterized epigenetic modification. In this paper, we briefly introduce DNA methylation mechanisms, genome-wide DNA methylation studies, and identify specific genomic methylation sites in individuals diagnosed with schizophrenia. The outline candidate genes such as Reelin and COMT, are also outlined before paying attention to the conundrum of recent researches.
C1 [Zong, Xiaofen; Hu, Maolin; Li, Zongchang; Chen, Xiaogang; Tang, Jinsong] Cent S Univ, Xiangya Hosp 2, Inst Mental Hlth, Changsha 410011, Hunan, Peoples R China.
[Cao, Hongbao] NIMH, Unit Stat Genom, NIH, Bethesda, MD 20852 USA.
[Chen, Xiaogang] Cent S Univ, Key Lab Psychiat & Mental Hlth Hunan Prov, Changsha 410011, Hunan, Peoples R China.
[Chen, Xiaogang] Cent S Univ, Natl Technol Inst Psychiat, Changsha 410011, Hunan, Peoples R China.
RP Chen, XG (reprint author), Cent S Univ, Xiangya Hosp 2, Inst Mental Hlth, Changsha 410011, Hunan, Peoples R China.
EM chenxghn@gmail.com; tangjinsonghn@gmail.com
FU National Natural Science Foundation of China [81271484, 81471361,
30900486, 81371480]; National Key Basic Research and Development Program
[2012CB517904]
FX This work was supported by the National Natural Science Foundation of
China (81271484 and 81471361 to X.C, 30900486 and 81371480 to J.T) and
the National Key Basic Research and Development Program (2012CB517904 to
X.C).
NR 59
TC 0
Z9 0
U1 4
U2 15
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 2095-9273
EI 2095-9281
J9 SCI BULL
JI Sci. Bull.
PD JAN
PY 2015
VL 60
IS 2
BP 149
EP 155
DI 10.1007/s11434-014-0690-y
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA5DA
UT WOS:000348927000001
ER
PT J
AU Rybicki, FJ
Mather, RT
Kumamaru, KK
Brinker, J
Chen, MY
Cox, C
Matheson, MB
Dewey, M
DiCarli, MF
Miller, JM
Geleijns, J
George, RT
Paul, N
Texter, J
Vavere, A
Yaw, TS
Lima, JAC
Clouse, ME
AF Rybicki, Frank J.
Mather, Richard T.
Kumamaru, Kanako K.
Brinker, Jeffrey
Chen, Marcus Y.
Cox, Christopher
Matheson, Matthew B.
Dewey, Marc
DiCarli, Marcelo F.
Miller, Julie M.
Geleijns, Jacob
George, Richard T.
Paul, Narinder
Texter, John
Vavere, Andrea
Yaw, Tan Swee
Lima, Joao A. C.
Clouse, Melvin E.
TI Comprehensive Assessment of Radiation Dose Estimates for the CORE320
Study
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE coronary angiography; coronary vessels; CT; radiation dose; SPECT
ID STRESS MYOCARDIAL-PERFUSION; CORONARY-ARTERY-DISEASE; CARDIAC
MAGNETIC-RESONANCE; DUAL-SOURCE CT; COMPUTED-TOMOGRAPHY ANGIOGRAPHY;
FRACTIONAL FLOW RESERVE; DIAGNOSTIC PERFORMANCE; DIPYRIDAMOLE STRESS;
320-MDCT ANGIOGRAPHY; INCREMENTAL VALUE
AB OBJECTIVE. The purpose of this study was to comprehensively study estimated radiation doses for subjects included in the main analysis of the Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography (CORE320) study (ClinicalTrials. gov identifier NCT00934037), a clinical trial comparing combined CT angiography (CTA) and perfusion CT with the reference standard catheter angiography plus myocardial perfusion SPECT.
SUBJECTS AND METHODS. Prospectively acquired data on 381 CORE320 subjects were analyzed in four groups of testing related to radiation exposure. Radiation dose estimates were compared between modalities for combined CTA and perfusion CT with respect to covariates known to influence radiation exposure and for the main clinical outcomes defined by the trial. The final analysis assessed variations in radiation dose with respect to several factors inherent to the trial.
RESULTS. The mean radiation dose estimate for the combined CTA and perfusion CT protocol (8.63 mSv) was significantly (p < 0.0001 for both) less than the average dose delivered from SPECT (10.48 mSv) and the average dose from diagnostic catheter angiography (11.63 mSv). There was no significant difference in estimated CTA-perfusion CT radiation dose for subjects who had false-positive or false-negative results in the CORE320 main analyses in a comparison with subjects for whom the CTA-perfusion CT findings were in accordance with the reference standard SPECT plus catheter angiographic findings.
CONCLUSION. Radiation dose estimates from CORE320 support clinical implementation of a combined CT protocol for assessing coronary anatomy and myocardial perfusion.
C1 [Rybicki, Frank J.; Kumamaru, Kanako K.] Brigham & Womens Hosp, Dept Radiol, Appl Imaging Sci Lab, Boston, MA 02115 USA.
[Rybicki, Frank J.; Kumamaru, Kanako K.; DiCarli, Marcelo F.; Clouse, Melvin E.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Mather, Richard T.] Toshiba Med Res Inst, Vernon Hills, IL USA.
[Brinker, Jeffrey; Miller, Julie M.; Texter, John; Vavere, Andrea; Lima, Joao A. C.] John Hopkins Hosp & Sch Med, Baltimore, MD USA.
[Cox, Christopher; Matheson, Matthew B.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Dewey, Marc] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[DiCarli, Marcelo F.] Charite, Berlin, Germany.
[Geleijns, Jacob] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Geleijns, Jacob] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Paul, Narinder] Toronto Gen Hosp, Toronto, ON, Canada.
[Yaw, Tan Swee] Natl Heart Ctr, Singapore, Singapore.
[Clouse, Melvin E.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
RP Rybicki, FJ (reprint author), Brigham & Womens Hosp, Dept Radiol, Appl Imaging Sci Lab, 75 Francis St, Boston, MA 02115 USA.
EM frybicki@partners.org
OI Dewey, Marc/0000-0002-4402-2733
FU Toshiba Medical Systems
FX M. Dewey, J. Brinker, C. Cox, M. F. DiCarli, R. T. George, J. M. Miller,
T. S. Yaw, A. Vavere, J. A. C. Lima, N. Paul, and F. J. Rybicki report
that their institutions receive grant support from Toshiba Medical
Systems. M. Dewey, T. S. Yaw, and N. Paul are on the speakers bureau for
Toshiba Medical Systems Corporation.
NR 68
TC 2
Z9 2
U1 0
U2 3
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JAN
PY 2015
VL 204
IS 1
BP W27
EP W36
DI 10.2214/AJR.13.12375
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AZ9UO
UT WOS:000348562300005
PM 25539270
ER
PT S
AU O'Shea, JJ
Schwartz, DM
Villarino, AV
Gadina, M
McInnes, IB
Laurence, A
AF O'Shea, John J.
Schwartz, Daniella M.
Villarino, Alejandro V.
Gadina, Massimo
McInnes, Iain B.
Laurence, Arian
BE Caskey, CT
TI The JAK-STAT Pathway: Impact on Human Disease and Therapeutic
Intervention
SO ANNUAL REVIEW OF MEDICINE, VOL 66
SE Annual Review of Medicine
LA English
DT Review; Book Chapter
DE cytokine; autoimmunity; immunodeficiency; cancer; kinase inhibitors
ID JANUS KINASE INHIBITOR; ACTIVE RHEUMATOID-ARTHRITIS; SEVERE COMBINED
IMMUNODEFICIENCY; GRANULAR LYMPHOCYTIC-LEUKEMIA; PLACEBO-CONTROLLED
TRIAL; LONG-TERM EXTENSION; HYPER-IGE SYNDROME; TOFACITINIB CP-690,550;
INADEQUATE RESPONSE; PLAQUE PSORIASIS
AB The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Genetic mutations and polymorphisms are functionally relevant to a variety of human diseases, especially cancer and immune-related conditions. The clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that targets JAKs.
C1 [O'Shea, John J.; Schwartz, Daniella M.; Villarino, Alejandro V.; Gadina, Massimo; McInnes, Iain B.; Laurence, Arian] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM osheajo@mail.nih.gov
RI Laurence, Arian/A-8770-2009;
OI Laurence, Arian/0000-0003-0942-8292; McInnes, Iain/0000-0002-6462-4280;
Villarino, Alejandro/0000-0001-8068-2176
NR 87
TC 81
Z9 81
U1 9
U2 44
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0066-4219
BN 978-0-8243-0566-6
J9 ANNU REV MED
JI Annu. Rev. Med.
PY 2015
VL 66
BP 311
EP 328
DI 10.1146/annurev-med-051113-024537
PG 18
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA BB9PT
UT WOS:000348560300021
PM 25587654
ER
PT S
AU Safronetz, D
Feldmann, H
de Wit, E
AF Safronetz, David
Feldmann, Heinz
de Wit, Emmie
BE Abbas, AK
Galli, SJ
Howley, PM
TI Birth and Pathogenesis of Rogue Respiratory Viruses
SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 10
SE Annual Review of Pathology-Mechanisms of Disease
LA English
DT Review; Book Chapter
DE emerging viruses; hantavirus pulmonary syndrome; Nipah virus disease;
Middle East respiratory syndrome
ID HANTAVIRUS PULMONARY SYNDROME; SIN-NOMBRE-VIRUS; SYNDROME CORONAVIRUS
INFECTION; DIPEPTIDYL PEPTIDASE 4; CENTRAL-NERVOUS-SYSTEM; NEW-WORLD
HANTAVIRUSES; INNATE IMMUNE-SYSTEM; LETHAL DISEASE-MODEL; SYRIAN-HAMSTER
MODEL; NIPAH-VIRUS
AB Emerging infectious diseases of zoonotic origin are shaping today's infectious disease field more than ever. In this article, we introduce and review three emerging zoonotic viruses. Novel hantaviruses emerged in the Americas in the mid-1990s as the cause of severe respiratory infections, designated hantavirus pulmonary syndrome, with case fatality rates of around 40%. Nipah virus emerged a few years later, causing respiratory infections and encephalitis in Southeast Asia, with case fatality rates ranging from 40% to more than 90%. A new coronavirus emerged in 2012 on the Arabian Peninsula with a clinical syndrome of acute respiratory infections, later designated as Middle East respiratory syndrome (MERS), and an initial case fatality rate of more than 40%. Our current state of knowledge on the pathogenicity of these three severe, emerging viral infections is discussed.
C1 [Safronetz, David; Feldmann, Heinz; de Wit, Emmie] NIAID, Lab Virol, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP Safronetz, D (reprint author), NIAID, Lab Virol, Div Intramural Res, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM safronetzd@niaid.nih.gov; feldmannh@niaid.nih.gov; emmie.deWit@nih.gov
OI de Wit, Emmie/0000-0002-9763-7758
FU Intramural NIH HHS
NR 143
TC 2
Z9 3
U1 1
U2 6
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 1553-4006
BN 978-0-8243-4310-1
J9 ANNU REV PATHOL-MECH
JI Annu. Rev. Pathol.-Mech Dis.
PY 2015
VL 10
BP 449
EP 471
DI 10.1146/annurev-pathol-012414-040501
PG 23
WC Pathology
SC Pathology
GA BB9PX
UT WOS:000348560600016
PM 25423349
ER
PT S
AU Insel, PA
Amara, SG
Blaschke, TF
AF Insel, Paul A.
Amara, Susan G.
Blaschke, Terrence F.
BE Insel, PA
TI Introduction to the Theme "Precision Medicine and Prediction in
Pharmacology"
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55
SE Annual Review of Pharmacology and Toxicology
LA English
DT Editorial Material; Book Chapter
C1 [Insel, Paul A.] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.
[Amara, Susan G.] NIMH, Bethesda, MD 20892 USA.
[Blaschke, Terrence F.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Blaschke, Terrence F.] Stanford Univ, Sch Med, Dept Clin Pharmacol, Stanford, CA 94305 USA.
RP Insel, PA (reprint author), Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA.
EM pinsel@ucsd.edu; susan.amara@nih.gov; blaschke@stanford.edu
NR 14
TC 2
Z9 2
U1 0
U2 9
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0455-3
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2015
VL 55
BP 11
EP 14
DI 10.1146/annurev-pharmtox-101714-123102
PG 4
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BB9PW
UT WOS:000348560500002
PM 25562643
ER
PT S
AU Nussinov, R
Tsai, CJ
AF Nussinov, Ruth
Tsai, Chung-Jung
BE Insel, PA
TI The Design of Covalent Allosteric Drugs
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE allosteric modulator; agonist; antagonist; pharmacology; toxicity;
allosteric drug discovery
ID PROTEIN-PROTEIN INTERACTIONS; HIV-1 REVERSE-TRANSCRIPTASE; INDUCED
LIVER-INJURY; IRREVERSIBLE INHIBITORS; ACQUIRED-RESISTANCE; KINASE
INHIBITORS; LUNG ADENOCARCINOMAS; FOLDING FUNNELS; RESIDENCE TIME; EGF
RECEPTOR
AB A key issue in drug discovery is how to reduce drug dosage and increase specificity while retaining or increasing efficacy, as high dosage is often linked to toxicity. There are two types of drugs on the market: orthosteric and allosteric. Orthosteric drugs can be noncovalent or covalent. The latter are advantageous because they may be prescribed in lower doses, but their potential off-target toxicity is a primary concern. The chief advantages of allosteric drugs are their higher specificity and their consequently lower chance of toxic side effects. Covalent allosteric drugs combine the pharmacological merits of covalent drugs with the additional benefit of the higher specificity of allosteric drugs. In a recent promising step in therapeutic drug development, allosteric, disulfide-tethered fragments successfully modulated the activity of a protein kinase and K-Ras.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM NussinoR@helix.nih.gov
FU Intramural NIH HHS; PHS HHS [HHSN261200800001E]
NR 104
TC 21
Z9 22
U1 11
U2 54
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0455-3
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2015
VL 55
BP 249
EP 267
DI 10.1146/annurev-pharmtox-010814-124401
PG 19
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BB9PW
UT WOS:000348560500015
PM 25149918
ER
PT S
AU Urban, DJ
Roth, BL
AF Urban, Daniel J.
Roth, Bryan L.
BE Insel, PA
TI DREADDs (Designer Receptors Exclusively Activated by Designer Drugs):
Chemogenetic Tools with Therapeutic Utility
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE synthetic biology; G protein-coupled receptors; GPCRs; systems biology;
drug discovery
ID PROTEIN-COUPLED RECEPTOR; TRANSLATIONAL PROFILING APPROACH; DIRECTED
MOLECULAR EVOLUTION; BETA-CELL FUNCTION; CLOZAPINE-N-OXIDE; IN-VIVO;
GENETIC IDENTIFICATION; G(Q)-COUPLED RECEPTOR; ALLOSTERIC MODULATION;
FEEDING-BEHAVIOR
AB In the past decade, emerging synthetic biology technologies such as chemogenetics have dramatically transformed how pharmacologists and systems biologists deconstruct the involvement of G protein-coupled receptors (GPCRs) in a myriad of physiological and translational settings. Here we highlight a specific chemogenetic application that extends the utility of the concept of RASSLs (receptors activated solely by synthetic ligands): We have dubbed it DREADDs (designer receptors exclusively activated by designer drugs). As we show in this review, DREADDs are now used ubiquitously to modulate GPCR activity noninvasively in vivo. Results from these studies have directly implicated GPCR signaling in a large number of therapeutically relevant contexts. We also highlight recent applications of DREADD technology that have illuminated GPCR signaling processes that control pathways relevant to the treatment of eating disorders, obesity, and obesity-associated metabolic abnormalities. Additionally, we provide an overview of the potential utility of chemogenetic technologies for transformative therapeutics.
C1 [Urban, Daniel J.; Roth, Bryan L.] UNC Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27514 USA.
RP Urban, DJ (reprint author), UNC Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010
NR 100
TC 90
Z9 90
U1 20
U2 64
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0455-3
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2015
VL 55
BP 399
EP 417
DI 10.1146/annurev-pharmtox-010814-124803
PG 19
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BB9PW
UT WOS:000348560500022
PM 25292433
ER
PT S
AU Radonjic-Hoesli, S
Valent, P
Klion, AD
Wechsler, ME
Simon, HU
AF Radonjic-Hoesli, Susanne
Valent, Peter
Klion, Amy D.
Wechsler, Michael E.
Simon, Hans-Uwe
BE Insel, PA
TI Novel Targeted Therapies for Eosinophil-Associated Diseases and Allergy
SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 55
SE Annual Review of Pharmacology and Toxicology
LA English
DT Review; Book Chapter
DE tyrosine kinase inhibitors; biologicals; asthma; chronic eosinophilic
leukemia; hypereosinophilic syndrome
ID CHRONIC MYELOID-LEUKEMIA; 8P11 MYELOPROLIFERATIVE SYNDROME; THYMIC
STROMAL LYMPHOPOIETIN; CRTH2 ANTAGONIST OC000459;
CHURG-STRAUSS-SYNDROME; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; CHRONIC
MYELOGENOUS LEUKEMIA; DUAL IL-4/IL-13 ANTAGONIST; TYROSINE KINASE
INHIBITOR; GROWTH-FACTOR RECEPTOR
AB Eosinophil-associated diseases often present with life-threatening manifestations and/or chronic organ damage. Currently available therapeutic options are limited to a few drugs that often have to be prescribed on a lifelong basis to keep eosinophil counts under control. In the past 10 years, treatment options and outcomes in patients with clonal eosinophilic and other eosinophilic disorders have improved substantially. Several new targeted therapies have emerged, addressing different aspects of eosinophil expansion and inflammation. In this review, we discuss available and currently tested agents as well as new strategies and drug targets relevant to both primary and secondary eosinophilic diseases, including allergic disorders.
C1 [Radonjic-Hoesli, Susanne; Simon, Hans-Uwe] Univ Bern, Inst Pharmacol, CH-3010 Bern, Switzerland.
[Valent, Peter] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, A-1090 Vienna, Austria.
[Klion, Amy D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wechsler, Michael E.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
RP Radonjic-Hoesli, S (reprint author), Univ Bern, Inst Pharmacol, CH-3010 Bern, Switzerland.
EM hus@pki.unibe.ch
OI Klion, Amy/0000-0002-4986-5326
FU Austrian Science Fund FWF [F 4704]; Intramural NIH HHS; NIAID NIH HHS
[U01 AI097073]
NR 152
TC 9
Z9 9
U1 1
U2 10
PU ANNUAL REVIEWS
PI PALO ALTO
PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA
SN 0362-1642
BN 978-0-8243-0455-3
J9 ANNU REV PHARMACOL
JI Annu. Rev. Pharmacol. Toxicol.
PY 2015
VL 55
BP 633
EP 656
DI 10.1146/annurev-pharmtox-010814-124407
PG 24
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA BB9PW
UT WOS:000348560500033
PM 25340931
ER
PT J
AU Suner, A
Karakulah, G
Dicle, O
Sokmen, S
Celikoglu, CC
AF Suner, A.
Karakuelah, G.
Dicle, O.
Soekmen, S.
Celikoglu, C. C.
TI corRECTreatment: A web-based decision support tool for rectal cancer
treatment that uses the analytic hierarchy process and decision tree
SO APPLIED CLINICAL INFORMATICS
LA English
DT Article
DE Clinical decision support; analytic hierarchy process; decision tree;
rectal cancer
ID COLORECTAL-CANCER; COST-EFFECTIVENESS; LIVER METASTASES; RISK-FACTORS;
PROCESS AHP; CARE; MANAGEMENT; DIAGNOSIS; COMMUNITY; THERAPY
AB Background: The selection of appropriate rectal cancer treatment is a complex multi-criteria decision making process, in which clinical decision support systems might be used to assist and enrich physicians' decision making.
Objective: The objective of the study was to develop a web-based clinical decision support tool for physicians in the selection of potentially beneficial treatment options for patients with rectal cancer.
Methods: The updated decision model contained 8 and 10 criteria in the first and second steps respectively. The decision support model, developed in our previous study by combining the Analytic Hierarchy Process (AHP) method which determines the priority of criteria and decision tree that formed using these priorities, was updated and applied to 388 patients data collected retrospectively. Later, a web-based decision support tool named corRECTreatment was developed. The compatibility of the treatment recommendations by the expert opinion and the decision support tool was examined for its consistency. Two surgeons were requested to recommend a treatment and an overall survival value for the treatment among 20 different cases that we selected and turned into a scenario among the most common and rare treatment options in the patient data set.
Results: In the AHP analyses of the criteria, it was found that the matrices, generated for both decision steps, were consistent (consistency ratio<0.1). Depending on the decisions of experts, the consistency value for the most frequent cases was found to be 80% for the first decision step and 100% for the second decision step. Similarly, for rare cases consistency was 50% for the first decision step and 80% for the second decision step.
Conclusions: The decision model and corRECTreatment, developed by applying these on real patient data, are expected to provide potential users with decision support in rectal cancer treatment processes and facilitate them in making projections about treatment options.
C1 [Suner, A.] Ege Univ, Sch Med, Dept Biostat & Med Informat, TR-35040 Izmir, Turkey.
[Karakuelah, G.] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Karakuelah, G.; Dicle, O.] Dokuz Eylul Univ, Hlth Sci Inst, Dept Med Informat, TR-35340 Izmir, Turkey.
[Dicle, O.] Dokuz Eylul Univ, Sch Med, Dept Radiol, TR-35340 Izmir, Turkey.
[Soekmen, S.] Dokuz Eylul Univ, Sch Med, Dept Gen Surg, Colorectal & Pelv Surg Unit, TR-35340 Izmir, Turkey.
[Celikoglu, C. C.] Dokuz Eylul Univ, Fac Sci, Dept Stat, TR-35160 Izmir, Turkey.
RP Suner, A (reprint author), Ege Univ, Sch Med, Dept Biostat & Med Informat, TR-35040 Izmir, Turkey.
EM aslisuner@gmail.com
RI SUNER, ASLI/C-1032-2012;
OI SUNER, ASLI/0000-0002-6872-9901; Karakulah, Gokhan/0000-0001-6706-1375
NR 38
TC 1
Z9 2
U1 3
U2 10
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 1869-0327
J9 APPL CLIN INFORM
JI Appl. Clin. Inform.
PY 2015
VL 6
IS 1
BP 56
EP 74
DI 10.4338/ACI-2014-10-RA-0087
PG 19
WC Medical Informatics
SC Medical Informatics
GA CA2EF
UT WOS:000348721000005
PM 25848413
ER
PT J
AU Veno, ST
Witt, MB
Kulikowicz, T
Bohr, VA
Stevnsner, T
AF Veno, Susanne T.
Witt, Marie B.
Kulikowicz, Tomasz
Bohr, Vilhelm A.
Stevnsner, Tinna
TI Regulation of the human Suv3 helicase on DNA by inorganic cofactors
SO BIOCHIMIE
LA English
DT Article
DE Helicase; Cofactor; Nucleotide; Divalent cations; DNA binding protein
ID YEAST MITOCHONDRIAL DEGRADOSOME; WERNER-SYNDROME PROTEIN; RNA HELICASE;
MAMMALIAN MITOCHONDRIA; TRYPANOSOMA-BRUCEI; RNA/DNA HELICASE; HSUV3P
HELICASE; REPLICATION; TURNOVER; RIBONUCLEOTIDES
AB Mitochondria are essential organelles and consequently proper expression and maintenance of the mitochondrial genome are indispensable for proper cell function. The mitochondrial Suv3 (SUPV3L1) helicase is known to have a central role in mitochondrial RNA metabolism and to be essential for maintenance of mitochondrial DNA stability. Here we have performed biochemical investigations to determine the potential regulation of the human Suv3 (hSuv3) helicase function by inorganic cofactors. We find that hSuv3 helicase and ATPase activity in vitro is strictly dependent on the presence of specific divalent cations. Interestingly, we show that divalent cations and nucleotide concentration have a direct effect on helicase substrate stability. Also, hSuy3 helicase is able to utilize several different nucleotide cofactors including both NTPs and dNTPs. Intriguingly, the potency of the individual nucleotide as energy source for hSuv3 unwinding differed depending on the included divalent cation and nucleotide concentration. At low concentrations, all four NTPs could support helicase activity with varying effectiveness depending on the included divalent cation. However, at higher nucleotide concentrations, only ATP was able to elicit the helicase activity of hSuv3. Consequently, we speculate that the capacity of hSuv3 DNA unwinding activity might be sensitive to the local availability of specific inorganic cofactors. (C) 2014 Elsevier B.V. and Societe francaise de biochimie et biologie Moleculaire (SFBBM). All rights reserved.
C1 [Veno, Susanne T.; Witt, Marie B.; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol & Genet, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark.
[Veno, Susanne T.; Witt, Marie B.; Stevnsner, Tinna] Univ Aarhus, Dept Mol Biol & Genet, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
[Kulikowicz, Tomasz; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Stevnsner, T (reprint author), Univ Aarhus, Dept Mol Biol & Genet, Danish Ctr Mol Gerontol, CF Moellers Alle,Bldg 1130, DK-8000 Aarhus C, Denmark.
EM tvs@mb.au.dk
FU Intramural Program of the National Institute on Aging, National
Institutes on Health; Velux Foundation
FX This work was supported by the Intramural Program of the National
Institute on Aging, National Institutes on Health and the Velux
Foundation.
NR 46
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0300-9084
EI 1638-6183
J9 BIOCHIMIE
JI Biochimie
PD JAN
PY 2015
VL 108
BP 160
EP 168
DI 10.1016/j.biochi.2014.11.003
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CA5PD
UT WOS:000348959400020
PM 25446650
ER
PT J
AU Cohen, EJ
Quarta, E
Fulgenzi, G
Minciacchi, D
AF Cohen, Erez James
Quarta, Eros
Fulgenzi, Gianluca
Minciacchi, Diego
TI Acetylcholine, GABA and neuronal networks: A working hypothesis for
compensations in the dystrophic brain
SO BRAIN RESEARCH BULLETIN
LA English
DT Review
DE Duchenne muscular dystrophy; Neuronal networks; mdx; Network
oscillations; Acetylcholine
ID DUCHENNE MUSCULAR-DYSTROPHY; LONG-TERM POTENTIATION; DEFICIENT MDX MICE;
CEREBELLAR PURKINJE-CELLS; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE;
SYNAPTIC PLASTICITY; RAT HIPPOCAMPUS; CHOLINERGIC MODULATION; GABAERGIC
INTERNEURONS
AB Duchenne muscular dystrophy (DMD), a genetic disease arising from a mutation in the dystrophin gene, is characterized by muscle failure and is often associated with cognitive deficits. Studies of the dystrophic brain on the murine mdx model of DMD provide evidence of morphological and functional alterations in the central nervous system (CNS) possibly compatible with the cognitive impairment seen in DMD. However, while some of the alterations reported are a direct consequence of the absence of dystrophin, others seem to be associated only indirectly. In this review we reevaluate the literature in order to formulate a possible explanation for the cognitive impairments associated with DMD. We present a working hypothesis, demonstrated as an integrated neuronal network model, according to which within the cascade of events leading to cognitive impairments there are compensatory mechanisms aimed to maintain functional stability via perpetual adjustments of excitatory and inhibitory components. Such ongoing compensatory response creates continuous perturbations that disrupt neuronal functionality in terms of network efficiency. We have theorized that in this process acetylcholine and network oscillations play a central role. A better understating of these mechanisms could provide a useful diagnostic index of the disease's progression and, perhaps, the correct counterbalance of this process might help to prevent deterioration of the CNS in DMD. Furthermore, the involvement of compensatory mechanisms in the CNS could be extended beyond DMD and possibly help to clarify other physio-pathological processes of the CNS. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Cohen, Erez James; Quarta, Eros; Minciacchi, Diego] Univ Florence, Dept Clin & Expt Med, Physiol Sci Sect, I-50134 Florence, Italy.
[Fulgenzi, Gianluca] Univ Politecn Marche, Dept Clin & Mol Sci, Lab Expt Pathol, Ancona, Italy.
[Fulgenzi, Gianluca] NCI, Neural Dev Sect, Mouse Canc Genet Program, Frederick, MD 21701 USA.
RP Minciacchi, D (reprint author), Univ Florence, Dept Clin & Expt Med, Physiol Sci Sect, Viale Morgagni 63, I-50134 Florence, Italy.
EM diego@unifi.it
OI Fulgenzi, Gianluca/0000-0003-2646-7728
NR 175
TC 4
Z9 4
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
EI 1873-2747
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD JAN
PY 2015
VL 110
BP 1
EP 13
DI 10.1016/j.brainresbull.2014.10.004
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CA4OK
UT WOS:000348884000001
PM 25445612
ER
PT J
AU Griffin, AJ
Crane, DD
Wehrly, TD
Bosio, CM
AF Griffin, Amanda J.
Crane, Deborah D.
Wehrly, Tara D.
Bosio, Catharine M.
TI Successful Protection against Tularemia in C57BL/6 Mice Is Correlated
with Expansion of Francisella tularensis-Specific Effector T Cells
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID LIVE VACCINE STRAIN; SCHU S4; LISTERIA-MONOCYTOGENES; RESPIRATORY
CHALLENGE; AEROSOL INFECTION; PURINE AUXOTROPH; GUINEA PIG; IMMUNITY;
IMMUNIZATION; PULMONARY
AB Francisella tularensis is an intracellular, Gram-negative bacterium that causes the fatal disease tularemia. Currently, there are no licensed vaccines for tularemia and the requirements for protection against infection are poorly defined. To identify correlates of vaccine-induced immunity against tularemia, we compared different strains of the live vaccine strain (LVS) for their relative levels of virulence and ability to protect C57BL/6 mice against challenge with virulent F. tularensis strain SchuS4. Successful vaccination, as defined by survival of C57BL/6 mice, was correlated with significantly greater numbers of effector T cells in the spleen and lung. Further, lung cells and splenocytes from fully protected animals were more effective than lung cells and splenocytes from vaccinated but nonimmune animals in limiting intracellular replication of SchuS4 in vitro. Together, our data provide a unique model to compare efficacious vaccines to nonefficacious vaccines, which will enable comprehensive identification of host and bacterial components required for immunization against tularemia.
C1 [Griffin, Amanda J.; Crane, Deborah D.; Wehrly, Tara D.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Bosio, CM (reprint author), NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM bosioc@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015
FU Intramural Research Program of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 42
TC 9
Z9 9
U1 1
U2 10
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 JAN
PY 2015
VL 22
IS 1
BP 119
EP 128
DI 10.1128/CVI.00648-14
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CA2YK
UT WOS:000348771800014
PM 25410207
ER
PT J
AU Hogan, MC
Abebe, K
Torres, VE
Chapman, AB
Bae, KT
Tao, C
Sun, HL
Perrone, RD
Steinman, TI
Braun, W
Winklhofer, FT
Miskulin, DC
Rahbari-Oskoui, F
Brosnahan, G
Masoumi, A
Karpov, IO
Spillane, S
Flessner, M
Moore, CG
Schrier, RW
AF Hogan, Marie C.
Abebe, Kaleab
Torres, Vicente E.
Chapman, Arlene B.
Bae, Kyongtae T.
Tao, Cheng
Sun, Hongliang
Perrone, Ronald D.
Steinman, Theodore I.
Braun, William
Winklhofer, Franz T.
Miskulin, Dana C.
Rahbari-Oskoui, Frederic
Brosnahan, Godela
Masoumi, Amirali
Karpov, Irina O.
Spillane, Susan
Flessner, Michael
Moore, Charity G.
Schrier, Robert W.
TI Liver Involvement in Early Autosomal-Dominant Polycystic Kidney Disease
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE HALT-PKD-A; Hepatic Cyst; CKD; MRI Analysis
ID NORMAL SPLENIC VOLUME; STAGE RENAL-DISEASE; HEPATIC CYSTS;
COMPUTED-TOMOGRAPHY; IMAGING EVALUATION; SOMATOSTATIN; ADULTS; CT;
HYPERTROPHY; ACQUISITION
AB BACKGROUND & AIMS: Polycystic liver disease (PLD), the most common extrarenal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent as a result of increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes are associated with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes.
METHODS: We performed a cross-sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I-converting enzyme inhibitor and angiotensin II-receptor blocker was superior to the inhibitor alone, and whether low blood pressure (< 110/75 mm Hg) was superior to standard blood pressure (120-130/70-80 mm Hg), in delaying renal cystic progression in 558 patients with ADPKD, stages 1 and 2 chronic kidney disease, and hypertension (age, 15-49 y).
RESULTS: We found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had a relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism were associated with PLD severity. Higher liver volumes were associated with a lower quality of life.
CONCLUSIONS: Hepatomegaly is common even in early stage ADPKD and is not accounted for by cysts alone. Parenchymal volumes were larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations, even among patients without cysts. The severity of PLD was associated with altered biochemical and hematologic features, as well as quality of life.
C1 [Hogan, Marie C.; Torres, Vicente E.] Mayo Clin, Coll Med, Rochester, MN 55905 USA.
[Abebe, Kaleab; Bae, Kyongtae T.; Tao, Cheng; Sun, Hongliang; Karpov, Irina O.; Spillane, Susan; Moore, Charity G.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Chapman, Arlene B.; Rahbari-Oskoui, Frederic] Emory Univ, Sch Med, Atlanta, GA USA.
[Perrone, Ronald D.; Miskulin, Dana C.] Tufts Med Ctr, Boston, MA USA.
[Steinman, Theodore I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Braun, William] Cleveland Clin, Cleveland, OH 44106 USA.
[Winklhofer, Franz T.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Brosnahan, Godela; Masoumi, Amirali; Schrier, Robert W.] Univ Colorado, Aurora, CO USA.
[Flessner, Michael] Natl Inst Diabet & Digest Dis, NIH, Bethesda, MD USA.
RP Hogan, MC (reprint author), Mayo Clin, Div Nephrol, 200 First St SW, Rochester, MN 55905 USA.
EM hogan.marie@mayo.edu
OI Moore, Charity/0000-0002-0060-0124; Abebe, Kaleab/0000-0002-3644-8419
FU National Institutes of Health [U01 DK082230]; Boehringer Ingelheim
Pharmaceuticals, Inc.
FX Supported by funding from the National Institutes of Health (U01
DK082230) and supported in part by Boehringer Ingelheim Pharmaceuticals,
Inc. Boehringer Ingelheim Pharmaceuticals, Inc, had no role in the
design, analysis, or interpretation of the results in this study and
were given the opportunity to review the manuscript for medical and
scientific accuracy as it relates to their respective substances as well
as intellectual property considerations.
NR 49
TC 18
Z9 18
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JAN
PY 2015
VL 13
IS 1
BP 155
EP +
DI 10.1016/j.cgh.2014.07.051
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ2BW
UT WOS:000348040500027
PM 25111236
ER
PT J
AU Ghany, MG
Perrillo, R
Li, RS
Belle, SH
Janssen, HLA
Terrault, NA
Shuhart, MC
Lau, DTY
Kim, WR
Fried, MW
Sterling, RK
Di Bisceglie, AM
Han, SHB
Ganova-Raeva, LM
Chang, KM
Lok, ASF
AF Ghany, Marc G.
Perrillo, Robert
Li, Ruosha
Belle, Steven H.
Janssen, Harry L. A.
Terrault, Norah A.
Shuhart, Margaret C.
Lau, Daryl T-Y.
Kim, W. Ray
Fried, Michael W.
Sterling, Richard K.
Di Bisceglie, Adrian M.
Han, Steven-Huy B.
Ganova-Raeva, Lilia Milkova
Chang, Kyong-Mi
Lok, Anna Suk-Fong
CA Hepatitis B Res Network
TI Characteristics of Adults in the Hepatitis B Research Network in North
America Reflect Their Country of Origin and Hepatitis B Virus Genotype
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE HBeAg; Chronic Hepatitis B Virus Infection; USA; ALT
ID UNITED-STATES; HBV INFECTION; EPIDEMIOLOGY; PREVALENCE; WORLDWIDE;
DISEASE; BURDEN; HEALTH
AB BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network.
METHODS: The HBRN collected data on the clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America.
RESULTS: Half of the subjects in the HBRN are men, and the median age is 42 years; 72% are Asian, 15% are black, and 11% are white; with 82% born outside of North America. The most common HBV genotype was B (39%); 74% of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log(10) IU/mL; 68% of male subjects and 67% of female subjects had alanine aminotransferase levels higher than the normal range.
CONCLUSIONS: The HBRN cohort is used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America.
C1 [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Perrillo, Robert] Baylor Univ, Med Ctr, Hepatol Div, Dallas, TX USA.
[Li, Ruosha; Belle, Steven H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Janssen, Harry L. A.] Toronto Western Hosp, Div Gastroenterol, Univ Hlth Network, Toronto, ON M5T 2S8, Canada.
[Janssen, Harry L. A.] Toronto Gen Hosp, Div Gastroenterol, Univ Hlth Network, Toronto, ON, Canada.
[Terrault, Norah A.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Shuhart, Margaret C.] Univ Washington, Harborview Med Ctr, Viral Hepatitis & Liver Clin, Seattle, WA 98104 USA.
[Lau, Daryl T-Y.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA.
[Kim, W. Ray] Stanford Univ, Sch Med, Div Gastroenterol, Palo Alto, CA 94304 USA.
[Fried, Michael W.] Univ N Carolina, Ctr Liver, Sect Hepatol, Chapel Hill, NC USA.
[Sterling, Richard K.] Virginia Commonwealth Univ Hlth Syst, Sect Hepatol, Richmond, VA USA.
[Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA.
[Han, Steven-Huy B.] Univ Calif Los Angeles, David Geffen Sch Med, Pfleger Liver Inst Clin, Los Angeles, CA 90095 USA.
[Ganova-Raeva, Lilia Milkova] Ctr Dis Control & Prevent, Div Viral Hepatitis, Mol Epidemiol & Bioinformat Sequencing Lab, Atlanta, GA USA.
[Chang, Kyong-Mi] Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Penn Ctr Viral Hepatitis, Philadelphia, PA 19104 USA.
[Lok, Anna Suk-Fong] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA.
RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, NIH, Bdg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM marcg@intra.niddk.nih.gov
OI Barritt, Alfred/0000-0002-4200-3256; Cloonan, Yona/0000-0003-3893-3693;
Wahed, Abdus/0000-0001-6911-7221
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK082872, DK082864, DK082874, U01 DK082944, DK082943, DK082919, DK
082843, DK082867, DK082923, DK082871, DK082927, DK082866, DK082863,
A-DK-3002-001]; National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health; Immunology Center (National
Institutes of Health/National Institute of Diabetes and Digestive and
Kidney Diseases, Center of Molecular Studies in Digestive and Liver
Diseases) [P30DK50306]; Immunology Center (National Institutes of Health
Public Health Service Research) [M01RR00040]; National Center for
Advancing Translational Sciences, National Institutes of Health
[UL1TR000058]; Clinical and Translational Science Awards [UL1TR000004,
UL1TR001111, UL1RR024986]; Gilead Sciences, Inc; Roche Molecular Systems
through National Institute of Diabetes and Digestive and Kidney Diseases
FX The Hepatitis B Research Network was funded by grants from the National
Institute of Diabetes and Digestive and Kidney Diseases to the following
investigators: U01 DK082872 (W.L.), DK082864 (S.B.), DK082874 (H.J.),
U01 DK082944 (N.T.), DK082943 (R.C.), DK082919 (D.T.-Y.L.), DK 082843
(L.R.R.), DK082867 (M.W.F.), DK082923 (R.K.S.), DK082871 (A.D.B.),
DK082927 (S.-H.B.H.), DK082866 (K.-M.C.), and DK082863 (A.S.-F.L.); an
interagency agreement with the National Institute of Diabetes and
Digestive and Kidney Diseases: A-DK-3002-001 (L.M.G.-R.); and support
from the intramural program, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health (M.G.G.).
Additional funding for this study was provided by the Immunology Center
(National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases, Center of Molecular Studies in Digestive
and Liver Diseases: P30DK50306; and a National Institutes of Health
Public Health Service Research grant: M01RR00040 to K.-M.C.), by the
National Center for Advancing Translational Sciences, National
Institutes of Health (UL1TR000058 to R.K.S.); and Clinical and
Translational Science Awards grants: UL1TR000004 (N.A.T.), UL1TR001111
(M.W.F.), and UL1RR024986 (A.S.-F.L.). Additional support was provided
by Gilead Sciences, Inc, and Roche Molecular Systems via a Cooperative
Research And Development Agreement through the National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 15
TC 11
Z9 11
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JAN
PY 2015
VL 13
IS 1
BP 183
EP 192
DI 10.1016/j.cgh.2014.06.028
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AZ2BW
UT WOS:000348040500032
PM 25010003
ER
PT J
AU Nunez, PL
Srinivasan, R
Fields, RD
AF Nunez, Paul L.
Srinivasan, Ramesh
Fields, R. Douglas
TI EEG functional connectivity, axon delays and white matter disease
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE White matter disease; Functional connectivity; Alpha rhythms;
Multi-scale dynamics; Axon propagation speed; Local networks; Global
dynamics; Cortico-cortical axons
ID HIGH-RESOLUTION EEG; TOP-DOWN INFLUENCES; SHORT-TERM-MEMORY; NEOCORTICAL
INTERACTIONS; STATISTICAL-MECHANICS; LOCAL NETWORKS; CONDUCTION TIME;
CEREBRAL-CORTEX; HUMAN BRAIN; DYNAMICS
AB Objective: Both structural and functional brain connectivities are closely linked to white matter disease. We discuss several such links of potential interest to neurologists, neurosurgeons, radiologists, and non-clinical neuroscientists.
Methods: Treatment of brains as genuine complex systems suggests major emphasis on the multi-scale nature of brain connectivity and dynamic behavior. Cross-scale interactions of local, regional, and global networks are apparently responsible for much of EEG's oscillatory behaviors. Finite axon propagation speed, often assumed to be infinite in local network models, is central to our conceptual framework.
Results: Myelin controls axon speed, and the synchrony of impulse traffic between distant cortical regions appears to be critical for optimal mental performance and learning.
Results: Several experiments suggest that axon conduction speed is plastic, thereby altering the regional and global white matter connections that facilitate binding of remote local networks.
Conclusions: Combined EEG and high resolution EEG can provide distinct multi-scale estimates of functional connectivity in both healthy and diseased brains with measures like frequency and phase spectra, covariance, and coherence.
Significance: White matter disease may profoundly disrupt normal EEG coherence patterns, but currently these kinds of studies are rare in scientific labs and essentially missing from clinical environments. (C) 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Nunez, Paul L.] Cognit Dissonance LLC, Encinitas, CA 92024 USA.
[Srinivasan, Ramesh] Univ Calif Irvine, Dept Cognit Sci, Irvine, CA 92617 USA.
[Srinivasan, Ramesh] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92617 USA.
[Fields, R. Douglas] NICHD, Sect Nervous Syst Dev & Plast, NIH, Bethesda, MD 20892 USA.
RP Nunez, PL (reprint author), Cognit Dissonance LLC, 1726 Sienna Canyon Dr, Encinitas, CA 92024 USA.
EM pnunez@tulane.edu
FU National Institutes of Health of the United States [2R01MH68004]
FX This research was supported by National Institutes of Health of the
United States Grant 2R01MH68004.
NR 112
TC 12
Z9 12
U1 3
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD JAN
PY 2015
VL 126
IS 1
BP 110
EP 120
DI 10.1016/j.clinph.2014.04.003
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AZ9UJ
UT WOS:000348561800016
PM 24815984
ER
PT J
AU Andres, SN
Schellenberg, MJ
Wallace, BD
Tumbale, P
Williams, RS
AF Andres, Sara N.
Schellenberg, Matthew J.
Wallace, Bret D.
Tumbale, Percy
Williams, R. Scott
TI Recognition and Repair of Chemically Heterogeneous Structures at DNA
Ends
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Review
DE DNA damage response; X-ray crystallography; cancer; neurodegeneration
ID STRAND-BREAK REPAIR; BASE EXCISION-REPAIR; APURINIC-APYRIMIDINIC SITES;
DEOXYRIBOSE PHOSPHATE LYASE; HUMAN POLYNUCLEOTIDE KINASE; MAMMALIAN
TOPOISOMERASE-I; DISEASE PROTEIN APRATAXIN; MAINTAIN GENOME INTEGRITY;
YEAST APN2 PROTEIN; POLYMERASE-BETA
AB Exposure to environmental toxicants and stressors, radiation, pharmaceutical drugs, inflammation, cellular respiration, and routine DNA metabolism all lead to the production of cytotoxic DNA strand breaks. Akin to splintered wood, DNA breaks are not clean. Rather, DNA breaks typically lack DNA 5-phosphate and 3-hydroxyl moieties required for DNA synthesis and DNA ligation. Failure to resolve damage at DNA ends can lead to abnormal DNA replication and repair, and is associated with genomic instability, mutagenesis, neurological disease, ageing and carcinogenesis. An array of chemically heterogeneous DNA termini arises from spontaneously generated DNA single-strand and double-strand breaks (SSBs and DSBs), and also from normal and/or inappropriate DNA metabolism by DNA polymerases, DNA ligases and topoisomerases. As a front line of defense to these genotoxic insults, eukaryotic cells have accrued an arsenal of enzymatic first responders that bind and protect damaged DNA termini, and enzymatically tailor DNA ends for DNA repair synthesis and ligation. These nucleic acid transactions employ direct damage reversal enzymes including Aprataxin (APTX), Polynucleotide kinase phosphatase (PNK), the tyrosyl DNA phosphodiesterases (TDP1 and TDP2), the Ku70/80 complex and DNA polymerase (POL). Nucleolytic processing enzymes such as the MRE11/RAD50/NBS1/CtIP complex, Flap endonuclease (FEN1) and the apurinic endonucleases (APE1 and APE2) also act in the chemical cleansing of DNA breaks to prevent genomic instability and disease, and promote progression of DNA- and RNA-DNA damage response (DDR and RDDR) pathways. Here, we provide an overview of cellular first responders dedicated to the detection and repair of abnormal DNA termini. Environ. Mol. Mutagen. 56:1-21, 2015. (c) 2014 Wiley Periodicals, Inc.
C1 [Andres, Sara N.; Schellenberg, Matthew J.; Wallace, Bret D.; Tumbale, Percy; Williams, R. Scott] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Williams, RS (reprint author), NIEHS, NIH, 111 TW Alexander Dr,F337,F3-03, Res Triangle Pk, NC 27709 USA.
EM williamsrs@niehs.nih.gov
RI Williams, Robert/A-6059-2015
FU US National Institutes of Health (NIH); National Institute of
Environmental Health Sciences (NIEHS) [1Z01ES102765]
FX Grant sponsor: Intramural Research Program of the US National Institutes
of Health (NIH) and National Institute of Environmental Health Sciences
(NIEHS) Projects; Grant number: 1Z01ES102765 (to R. S. W.).
NR 226
TC 18
Z9 18
U1 1
U2 20
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 JAN
PY 2015
VL 56
IS 1
BP 1
EP 21
DI 10.1002/em.21892
PG 21
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA CA0ZC
UT WOS:000348641000001
PM 25111769
ER
PT J
AU Mendola, P
Mumford, SL
Mannisto, TI
Holston, A
Reddy, UM
Laughon, SK
AF Mendola, Pauline
Mumford, Sunni L.
Mannisto, Tuija I.
Holston, Alexander
Reddy, Uma M.
Laughon, S. Katherine
TI Controlled Direct Effects of Preeclampsia on Neonatal Health After
Accounting for Mediation by Preterm Birth
SO EPIDEMIOLOGY
LA English
DT Article
ID MARGINAL STRUCTURAL MODELS; CEREBRAL-PALSY; ANGIOGENIC FACTORS;
GESTATIONAL-AGE; AMNIOTIC-FLUID; RISK; COHORT; PREGNANCY; COMPLICATIONS;
EPIDEMIOLOGY
AB Background: Preeclampsia is characterized by alterations in angiogenic factors that may increase neonatal morbidity independent of preterm birth.
Methods: We estimated the controlled direct effect of preeclampsia on neonatal outcomes independent of preterm birth among 200,103 normotensive and 10,507 preeclamptic singleton pregnancies in the Consortium on Safe Labor (2002-2008). Marginal structural models with stabilized inverse probability weights accounted for potential confounders in the pathway from preeclampsia to preterm birth to neonatal outcomes, including mediator-outcome confounders related to preeclampsia status, such as cesarean delivery. Controlled direct effects of preeclampsia on perinatal mortality, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, respiratory distress syndrome, transient tachypnea of the newborn, anemia, apnea, asphyxia, peri-or intraventricular hemorrhage, and cardiomyopathy were estimated for the hypothesized intervention of term delivery for all infants.
Results: When delivery was set at >= 37 weeks, preeclampsia increased the odds of perinatal mortality (odds ratio = 2.2 [95% confidence interval = 1.1-4.5], SGA = (1.9 [1.8-2.1]), NICU admission (1.9 [1.7-2.1]), respiratory distress syndrome (2.8 [2.0-3.7], transient tachypnea of the newborn (1.6 [1.3-1.9]), apnea (2.2 [1.6-3.1]), asphyxia (2.7 [1.5-4.9]), and peri-or intraventricular hemorrhage (3.2 [1.4-7.7]). No direct effect of preeclampsia at term was observed for anemia or cardiomyopathy. Our results appear robust in the presence of moderate confounding, and restriction to severe preeclampsia yielded similar findings.
Conclusion: Preeclampsia was directly associated with adverse neonatal outcomes beyond morbidity mediated by preterm birth. Although severe neonatal outcomes were less common at later gestational ages, marginal structural models suggested elevated neonatal risk due to preeclampsia even if it was possible to deliver all infants at term.
C1 [Mendola, Pauline; Mumford, Sunni L.; Mannisto, Tuija I.; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
[Mannisto, Tuija I.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Diabet Prevent Unit, Oulu, Finland.
[Holston, Alexander] Naval Med Ctr Portsmouth, Dept Pediat, Portsmouth, VA USA.
[Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Extramural Res, Rockville, MD 20852 USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03F, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mannisto, Tuija/0000-0002-6382-9153; Mendola,
Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the National Institutes of Health, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health [HHSN267200603425C]
FX Supported by the Intramural Research Program of the National Institutes
of Health, Eunice Kennedy Shriver National Institute of Child Health and
Human Development. The Consortium on Safe Labor was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health through Contract No. HHSN267200603425C.
NR 35
TC 11
Z9 11
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD JAN
PY 2015
VL 26
IS 1
BP 17
EP 26
DI 10.1097/EDE.0000000000000213
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AU8XZ
UT WOS:000345878000016
PM 25437315
ER
PT J
AU Hofmann, JN
Corley, DA
Zhao, WK
Colt, JS
Shuch, B
Chow, WH
Purdue, MP
AF Hofmann, Jonathan N.
Corley, Douglas A.
Zhao, Wei K.
Colt, Joanne S.
Shuch, Brian
Chow, Wong-Ho
Purdue, Mark P.
TI Chronic Kidney Disease and Risk of Renal Cell Carcinoma: Differences by
Race
SO EPIDEMIOLOGY
LA English
DT Article
ID CANCER-RISK; ALCOHOL INTAKE; UNITED-STATES; TRANSPLANTATION;
HYPERTENSION; AMERICANS; DIALYSIS; ASSOCIATION; WHITE; APOL1
AB Background: The incidence of renal cell carcinoma in the United States differs by race/ethnicity. To better understand these disparities, we conducted a nested case-control study investigating renal cell carcinoma risk factors across racial/ethnic groups within the Kaiser Permanente Northern California health care network.
Methods: Our study included 3136 renal cell carcinoma cases (2152 whites, 293 blacks, 425 Hispanics, and 255 Asians) diagnosed between 1998 and 2008 and 31031 individually matched controls (21478 whites, 2836 blacks, 4147 Hispanics, and 2484 Asians). Risk of renal cell carcinoma was assessed in relation to smoking status, body mass index (BMI), hypertension, and chronic kidney disease. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, and population attributable risk (PAR) to estimate by race the proportion of cases attributable to hypertension and chronic kidney disease.
Results: The association between chronic kidney disease and renal cell carcinoma differed markedly by race (P-interaction < 0.001), with associations observed among blacks (OR = 10.4 [95% CI = 6.0-17.9]), Asians (5.1 [2.2-11.7]), and Hispanics (2.3 [1.1-4.6]) but not whites (1.1 [0.6-1.9]). Hypertension, high BMI, and smoking were associated with renal cell carcinoma, but findings generally did not differ by race. Relative to other racial/ethnic groups, blacks had the highest proportion of renal cell carcinoma incidence attributable to hypertension and chronic kidney disease (combined, PAR = 37%; hypertension only, PAR = 27%; chronic kidney disease, PAR = 10%).
Conclusions: Our findings suggest that hypertension and chronic kidney disease likely have contributed to the observed excess in renal cell carcinoma incidence among blacks compared with whites.
C1 [Hofmann, Jonathan N.; Colt, Joanne S.; Purdue, Mark P.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Corley, Douglas A.; Zhao, Wei K.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Shuch, Brian] Yale Univ, Sch Med, Dept Urol, New Haven, CT USA.
[Chow, Wong-Ho] Univ Texas Houston, Dept Epidemiol, Houston, TX USA.
[Purdue, Mark P.] Ontario Inst Canc Res, Toronto, ON, Canada.
RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 6E132, 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 Institutes of Health
FX Supported by Intramural Research Program of the National Institutes of
Health.
NR 20
TC 6
Z9 7
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD JAN
PY 2015
VL 26
IS 1
BP 59
EP 67
DI 10.1097/EDE.0000000000000205
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AU8XZ
UT WOS:000345878000021
PM 25393631
ER
PT J
AU Mumford, SL
Schisterman, EF
Cole, SR
Westreich, D
Platt, RW
AF Mumford, Sunni L.
Schisterman, Enrique F.
Cole, Stephen R.
Westreich, Daniel
Platt, Robert W.
TI Time at Risk and Intention-to-treat Analyses Parallels and Implications
for Inference
SO EPIDEMIOLOGY
LA English
DT Article
ID IMMORTAL PERSON-TIME; SUN EXPOSURE; STATISTICAL-MODELS; SKIN-CANCER;
BIAS; PREGNANCY; COHORT; FECUNDABILITY; NONCOMPLIANCE; CONCEPTION
AB Although the standard recommendation is to exclude person-time not at risk (ie, time during which the outcome could not have occurred) from the denominators of disease rates, there are scenarios where person-time not at risk should be included. In particular, we draw an analogy between including person-time not at risk and intention-to-treat (IT) analyses of randomized trials, and excluding person-time not at risk and compliance-corrected analysis of these same trials. Excluding person-time not at risk is appropriate when addressing questions of the biologic or mechanistic effects of an exposure, whereas the IT-type approach typically addresses questions regarding the effect of an exposure under observed compliance patterns. The choice of approach directly affects the causal question being addressed and subsequent inference, with potential implications for public health. When interested in estimating treatment effects that allow and account for potential noncompliance, or where the exposure may be associated with the time at risk, we argue that person-time not at risk should be included. In the case of time to pregnancy, although the IT-type analysis may underestimate the biological fecundity of the population, it may also yield an answer to a question that is of more interest to couples trying to become pregnant.
C1 [Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Cole, Stephen R.; Westreich, Daniel] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Platt, Robert W.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
RP Mumford, SL (reprint author), NICHD, Epidemiol Branch, DIPHR, 6100 Execut Blvd 7B03, Rockville, MD 20852 USA.
EM mumfords@mail.nih.gov
OI Platt, Robert/0000-0002-5981-8443; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the NIH, Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Long-Range Research
Initiative of the American Chemistry Council; National Scholar
(Chercheur-national) award from the Fonds de Recherche du Quebec-Sante
(FQR-S); FQR-S
FX Supported by the Intramural Research Program of the NIH, Eunice Kennedy
Shriver National Institute of Child Health and Human Development, and by
the Long-Range Research Initiative of the American Chemistry Council.
Robert W. Platt is supported by a National Scholar (Chercheur-national)
award from the Fonds de Recherche du Quebec-Sante (FQR-S) and is a
member of the Research Institute of the McGill University Health Centre,
which receives core funding from the FQR-S.
NR 38
TC 1
Z9 1
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD JAN
PY 2015
VL 26
IS 1
BP 112
EP 118
DI 10.1097/EDE.0000000000000188
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AU8XZ
UT WOS:000345878000028
PM 25275571
ER
PT J
AU Tseng, WL
Bones, BL
Kayser, RR
Olsavsky, AK
Fromm, SJ
Pine, DS
Leibenluft, E
Brotman, MA
AF Tseng, W. -L.
Bones, B. L.
Kayser, R. R.
Olsavsky, A. K.
Fromm, S. J.
Pine, D. S.
Leibenluft, E.
Brotman, M. A.
TI An fMRI study of emotional face encoding in youth at risk for bipolar
disorder
SO EUROPEAN PSYCHIATRY
LA English
DT Article
DE fMRI; Pediatric bipolar disorder; At risk; Face memory; Endophenotype
ID RATING-SCALE; DYSREGULATION; RELIABILITY; ACTIVATION; VALIDITY; MEMORY;
MANIA
AB Face memory deficits may be a bipolar disorder (BD) endophenotype. BD (n = 27) and unaffected youth at risk (n = 13) exhibited middle frontal gyrus hypoactivation during successful vs. unsuccessful encoding. Parahippocampal gyrus dysfunction was found in BD and at-risk youth (vs. low-risk, n = 37). Middle occipital gyrus hypoactivation was only present in BD. (C) 2014 Elsevier Masson SAS. All rights reserved.
C1 [Tseng, W. -L.; Fromm, S. J.; Pine, D. S.; Leibenluft, E.; Brotman, M. A.] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Bones, B. L.; Kayser, R. R.] Georgetown Univ, Sch Med, Washington, DC USA.
[Olsavsky, A. K.] UCLA Semel Inst Neurosci & Human Behav, Los Angeles, CA USA.
RP Tseng, WL (reprint author), Bldg 15K,Room 208,MSC 2670,15K North Dr, Bethesda, MD 20892 USA.
EM wan-ling.tseng@nih.gov
RI Brotman, Melissa/H-7409-2013
FU Intramural Research Program of the NIMH; NIH; Pfizer Inc.
FX This research was supported (in part) by the Intramural Research Program
of the NIMH. Dr. Olsavsky's research was made possible through the
Clinical Research Training Program, a public-private partnership
supported jointly by the NIH and Pfizer Inc. (via a grant to the
Foundation for NIH from Pfizer Inc.).
NR 17
TC 8
Z9 8
U1 2
U2 9
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0924-9338
EI 1778-3585
J9 EUR PSYCHIAT
JI Eur. Psychiat.
PD JAN
PY 2015
VL 30
IS 1
DI 10.1016/j.eurpsy.2014.05.004
PG 5
WC Psychiatry
SC Psychiatry
GA AZ1YX
UT WOS:000348032300016
PM 25172156
ER
PT J
AU Crosslin, DR
Carrell, DS
Burt, A
Kim, DS
Underwood, JG
Hanna, DS
Comstock, BA
Baldwin, E
de Andrade, M
Kullo, IJ
Tromp, G
Kuivaniemi, H
Borthwick, KM
McCarty, CA
Peissig, PL
Doheny, KF
Pugh, E
Kho, A
Pacheco, J
Hayes, MG
Ritchie, MD
Verma, SS
Armstrong, G
Stallings, S
Denny, JC
Carroll, RJ
Crawford, DC
Crane, PK
Mukherjee, S
Bottinger, E
Li, R
Keating, B
Mirel, DB
Carlson, CS
Harley, JB
Larson, EB
Jarvik, GP
AF Crosslin, D. R.
Carrell, D. S.
Burt, A.
Kim, D. S.
Underwood, J. G.
Hanna, D. S.
Comstock, B. A.
Baldwin, E.
de Andrade, M.
Kullo, I. J.
Tromp, G.
Kuivaniemi, H.
Borthwick, K. M.
McCarty, C. A.
Peissig, P. L.
Doheny, K. F.
Pugh, E.
Kho, A.
Pacheco, J.
Hayes, M. G.
Ritchie, M. D.
Verma, S. S.
Armstrong, G.
Stallings, S.
Denny, J. C.
Carroll, R. J.
Crawford, D. C.
Crane, P. K.
Mukherjee, S.
Bottinger, E.
Li, R.
Keating, B.
Mirel, D. B.
Carlson, C. S.
Harley, J. B.
Larson, E. B.
Jarvik, G. P.
TI Genetic variation in the HLA region is associated with susceptibility to
herpes zoster
SO GENES AND IMMUNITY
LA English
DT Article
ID ELECTRONIC MEDICAL-RECORDS; EMERGE NETWORK; RISK-FACTOR; POPULATION;
INFORMATION; HAPLOTYPE; TOOL
AB Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22 981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 x 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.
C1 [Crosslin, D. R.; Burt, A.; Kim, D. S.; Jarvik, G. P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Crosslin, D. R.; Kim, D. S.; Underwood, J. G.; Hanna, D. S.; Jarvik, G. P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Carrell, D. S.; Baldwin, E.; Larson, E. B.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Comstock, B. A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[de Andrade, M.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA.
[Kullo, I. J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Tromp, G.; Kuivaniemi, H.; Borthwick, K. M.] Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.
[McCarty, C. A.] Essentia Inst Rural Hlth, Duluth, MN USA.
[McCarty, C. A.; Peissig, P. L.] Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI 54449 USA.
[Doheny, K. F.; Pugh, E.] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA.
[Kho, A.; Pacheco, J.] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA.
[Kho, A.; Pacheco, J.] Northwestern Univ, Feinberg Sch Med, Div Prevent Med, Chicago, IL 60611 USA.
[Hayes, M. G.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[Ritchie, M. D.; Verma, S. S.; Armstrong, G.] Penn State Univ, Dept Biochem & Mol Biol, Ctr Syst Genom, University Pk, PA 16802 USA.
[Stallings, S.; Denny, J. C.; Carroll, R. J.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA.
[Crawford, D. C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Crawford, D. C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Crane, P. K.; Mukherjee, S.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA.
[Bottinger, E.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Li, R.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Keating, B.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Mirel, D. B.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Carlson, C. S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Harley, J. B.] BCH, CCHMC, Boston, MA USA.
RP Crosslin, DR (reprint author), Univ Washington, Dept Med, Div Med Genet, 1705 NE Pacific St,K253,Box 357720, Seattle, WA 98195 USA.
EM davidcr@u.washington.edu
OI Kuivaniemi, Helena/0000-0001-5753-8766
FU National Human Genome Research Institute (NHGRI), a component of the
National Institutes of Health (NIH), Bethesda, MD, USA [U01HG006375,
U01HG006382, U01HG006379, U01HG006389, U01HG006388, HG004438, HG004424,
U01HG006378, U01HG006385, U01HG006380, U01HG006828, U01HG006830]; State
of Washington Life Sciences Discovery Fund award
FX We are grateful to all the participants of the eMERGE study. This study
was supported by the following U01 grants from the National Human Genome
Research Institute (NHGRI), a component of the National Institutes of
Health (NIH), Bethesda, MD, USA: (1) U01HG006375 (Group
Health/University of Washington); (2) U01HG006382 (Geisinger Health
System); (3) U01HG006379 (Mayo Clinic); (4) U01HG006389 (Essentia Health
and Marshfield Clinic Research Foundation); (5) U01HG006388
(Northwestern University); (6) HG004438 (Center for Inherited Disease
Research, Johns Hopkins University); (7) HG004424 (Broad Institute of
Harvard and MIT); (8) U01HG006378, U01HG006385, U01HG006385 (Vanderbilt
University); (9) U01HG006380 (The Mt Sinai Hospital); (10) U01HG006828
(Cincinnati Children's Hospital Medical Center/Harvard); and (11)
U01HG006830 (Children's Hospital of Philadelphia). Additional support
was provided by a State of Washington Life Sciences Discovery Fund award
to the Northwest Institute of Genetic Medicine (to GPJ).
NR 26
TC 8
Z9 8
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
EI 1476-5470
J9 GENES IMMUN
JI Genes Immun.
PD JAN-FEB
PY 2015
VL 16
IS 1
BP 1
EP 7
DI 10.1038/gene.2014.51
PG 7
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA AZ6WG
UT WOS:000348358100001
PM 25297839
ER
PT J
AU Moon, HY
AF Moon, Hyo Youl
TI N-methyl D-aspartate receptor synaptonuclear signaling and neuronal
migration factor (Nsmf) plays a novel role in myoblast proliferation
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Article
DE Nsmf; Myocyte; Proliferation
ID MUSCULAR-ATROPHY; HYPOGONADISM; TESTOSTERONE; THERAPIES; MICE
AB Myogenesis, the formation and regeneration of muscular tissue, is a fundamental factor in embryonic development. N-methyl d-aspartate (NMDA) receptor synaptonuclear signaling and neuronal migration factor (Nsmf) mediates NMDA receptor endocytosis in GnRH neuronal cells. NMDA receptor is involved in myoblast differentiation by regulating Ca-2 (+) dependent fusion of myocytes. In this study, we investigated the role of Nsmf in myoblast proliferation and differentiation. Quantitative-PCR, immunoblotting, and immunohistochemistry results showed that the Nsmf expression levels increased during both the differentiation and proliferation of myocytes. Knockdown of Nsmf in myocytes by siRNA did not affect the myocyte differentiation marker myogenin. However, flow cytometry showed that the proliferation rate of the Nsmf-knockdown cells was reduced compared to the control cells. Therefore, our results indicate that Nsmf is a novel myogenic factor that can enhance myoblast proliferation. Furthermore, Nsmf may be an important therapeutic target in diseases associated with aging, muscular dystrophy, or cachexia.
C1 [Moon, Hyo Youl] Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, South Korea.
[Moon, Hyo Youl] NIA, Neuroplast & Behav Unit, Lab Neurosci, NIH, Baltimore, MD 21224 USA.
[Moon, Hyo Youl] NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Moon, HY (reprint author), Pohang Univ Sci & Technol, Sch Interdisciplinary Biosci & Bioengn, Pohang 790784, South Korea.
EM hymoon@postech.ac.kr
FU Korea Health Technology R&D Project through Korea Health Industry
Development Institute (KHIDI) - Ministry of Health & Welfare, Republic
of Korea [HI13C1149]
FX This research was supported by a grant of the Korea Health Technology
R&D Project through the Korea Health Industry Development Institute
(KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea
(grant number: HI13C1149).
NR 19
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1071-2690
EI 1543-706X
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD JAN
PY 2015
VL 51
IS 1
BP 79
EP 84
DI 10.1007/s11626-014-9811-9
PG 6
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA CA6AF
UT WOS:000348989700011
PM 25248434
ER
PT J
AU Orsega, S
AF Orsega, Susan
TI Adult HIV Infection Treatment Update 2014: An Approach to HIV Infection
Management and Antiretroviral Treatment
SO JNP-JOURNAL FOR NURSE PRACTITIONERS
LA English
DT Article
DE adherence; antiretroviral therapy; HIV management; HIV/AIDS
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-OUTCOMES; NEVIRAPINE USE;
THERAPY; RISK; AIDS; SOCIETY; HAART
AB It is critically important to keep up with the continuous advances in HIV treatment. With the key understanding of viral replication, combination therapy, treatment failure, and drug toxicities, the nurse practitioner has the knowledge to assist in monitoring the HIV patient. The purpose of this article is to provide an overview of the general principles of HIV disease and antiretroviral therapy, clarify the nurse practitioners role in how to manage patients receiving these medications, and present useful guidelines.
C1 NIAID, United States Publ Hlth Serv, NIH, Bethesda, MD 20892 USA.
RP Orsega, S (reprint author), NIAID, United States Publ Hlth Serv, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM susan.orsega@nih.gov
NR 32
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1555-4155
EI 1878-058X
J9 JNP-J NURSE PRACT
JI JNP-J. Nurse Pract.
PD JAN
PY 2015
VL 11
IS 1
BP 95
EP 102
DI 10.1016/j.nurpra.2014.10.034
PG 8
WC Nursing
SC Nursing
GA CA1TS
UT WOS:000348694900018
ER
PT J
AU Hartman, HN
Niemela, J
Hintermeyer, MK
Garofalo, M
Stoddard, J
Verbsky, JW
Rosenzweig, SD
Routes, JM
AF Hartman, Heather N.
Niemela, Julie
Hintermeyer, Mary K.
Garofalo, Mary
Stoddard, Jennifer
Verbsky, James W.
Rosenzweig, Sergio D.
Routes, John M.
TI Gain of Function Mutations of PIK3CD as a Cause of Primary Sclerosing
Cholangitis
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE PIK3CD; immunodeficiency; primary sclerosing cholangitis; recurrent
infections
ID HYPER-IGM SYNDROME
AB Gain of function (GOF) mutation in the p110 delta catalytic subunit of the phosphatidylinositol-3-OH kinase (PIK3CD) is the cause of a primary immunodeficiency (PID) characterized by recurrent sinopulmonary infections and lymphoproliferation. We describe a family of two adults and three children with GOF mutation in PIK3CD, all with recurrent sinopulmonary infections and varied infectious and non-infectious complications. The two adults have Primary Sclerosing Cholangitis (PSC) without evidence of Cryptosporidium parvum infection and have required liver transplantation. PSC is a novel phenotype of GOF mutation in PIK3CD.
C1 [Hartman, Heather N.; Verbsky, James W.; Routes, John M.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Hartman, Heather N.; Routes, John M.] Med Coll Wisconsin, Div Allergy Clin Immunol, Milwaukee, WI 53226 USA.
[Hintermeyer, Mary K.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Garofalo, Mary; Rosenzweig, Sergio D.] NIH, Primary Immunodeficiency Clin, Bethesda, MD 20892 USA.
[Verbsky, James W.] Med Coll Wisconsin, Div Rheumatol, Milwaukee, WI 53226 USA.
[Routes, John M.] Med Coll Wisconsin, MACC Fund Res Ctr, Milwaukee, WI 53226 USA.
RP Rosenzweig, SD (reprint author), NIH, Primary Immunodeficiency Clin, 10 Ctr Dr,Clin Ctr,2C410F, Bethesda, MD 20892 USA.
EM srosenzweig@cc.nih.gov; jroutes@mcw.edu
OI Niemela, Julie/0000-0003-4197-3792
FU Intramural NIH HHS [Z99 CL999999]
NR 11
TC 9
Z9 10
U1 1
U2 3
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 JAN
PY 2015
VL 35
IS 1
BP 11
EP 14
DI 10.1007/s10875-014-0109-1
PG 4
WC Immunology
SC Immunology
GA CA3KR
UT WOS:000348805600002
PM 25352054
ER
PT J
AU Brohl, AS
Stinson, JR
Su, HC
Badgett, T
Jennings, CD
Sukumar, G
Sindiri, S
Wang, W
Kardava, L
Moir, S
Dalgard, CL
Moscow, JA
Khan, J
Snow, AL
AF Brohl, Andrew S.
Stinson, Jeffrey R.
Su, Helen C.
Badgett, Thomas
Jennings, Chester D.
Sukumar, Gauthaman
Sindiri, Sivasish
Wang, Wei
Kardava, Lela
Moir, Susan
Dalgard, Clifton L.
Moscow, Jeffrey A.
Khan, Javed
Snow, Andrew L.
TI Germline CARD11 Mutation in a Patient with Severe Congenital B Cell
Lymphocytosis
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE CARD11; B-cell lymphocytosis; congenital; NF-kappa B; BENTA
ID NF-KAPPA-B; COMBINED IMMUNODEFICIENCY; CYCLIN G2; LYMPHOMA;
PROLIFERATION; DOMAIN; GENES; COOPERATION; EXPRESSION; PROTEIN
AB Activating germline mutations in CARD11 have recently been linked to a rare genetic disorder associated with congenital B cell lymphocytosis. We describe a patient with a similar clinical phenotype who had a de novo germline G123D CARD11 mutation.
Whole exome sequencing was performed on DNA from the patient and his biological parents. Laboratory studies examined characteristics of the patient's B and T lymphocytes. A CARD11 cDNA containing the mutation was transfected into a lymphocyte cell line to gain an understanding of its function. RNA sequencing was performed on samples from the patient and from patients with alternate germline CARD11 mutations and differential gene expression analysis was performed.
The patient had a decade-long history of severe polyclonal B lymphocytosis in the 20,000-90,000 lymphocytes/mm(3) range, which was markedly exacerbated by EBV infection and splenectomy at different times. He had a heterozygous germline CARD11 mutation causing a G123D amino acid substitution, which was demonstrated to induce NF-kappa B activation in unstimulated lymphocytes. In contrast to previous patients with CARD11 mutations, this patient's B cells exhibited higher expression of several cell cycle progression genes, as well as enhanced proliferation and improved survival following B cell receptor stimulation.
This is the third reported germline and first de novo CARD11 mutation shown to cause congenital B cell lymphocytosis. The mutation was associated with a dramatically greater lymphocytosis than in previously described cases, disproportionate to the level of constitutive NF-kappa B activation. However, comparative review of the patient's clinical history, combined with additional genomic and functional analyses, underscore other important variables that may affect pathophysiology or regulate mutant CARD11 function in B cell proliferation and disease. We now refer to these patients as having BENTA disease (B cell Expansion with NF-kappa B and T cell Anergy).
C1 [Brohl, Andrew S.; Sindiri, Sivasish; Khan, Javed] NCI, Ctr Canc Res, NIH, Oncogen Sect Genet Branch, Bethesda, MD 20892 USA.
[Stinson, Jeffrey R.; Snow, Andrew L.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Badgett, Thomas; Moscow, Jeffrey A.] Univ Kentucky, Dept Pediat, Lexington, KY USA.
[Badgett, Thomas; Moscow, Jeffrey A.] Univ Kentucky, Coll Med, Markey Canc Ctr, Lexington, KY USA.
[Jennings, Chester D.] Univ Kentucky, Coll Med, Dept Pathol, Lexington, KY USA.
[Sukumar, Gauthaman; Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Wang, Wei; Kardava, Lela; Moir, Susan] NIAID, Immunoregulat Lab, NIH, Immunopathogenesis Sect, Bethesda, MD 20892 USA.
RP Khan, J (reprint author), NCI, Ctr Canc Res, NIH, Oncogen Sect Genet Branch, 37 Convent Dr,Bldg 37,Room 2016B, Bethesda, MD 20892 USA.
EM khanjav@mail.nih.gov; andrew.snow@usuhs.edu
RI Su, Helen/H-9541-2015; Khan, Javed/P-9157-2014;
OI Su, Helen/0000-0002-5582-9110; Khan, Javed/0000-0002-5858-0488; sindiri,
sivasish/0000-0003-2516-969X; Snow, Andrew/0000-0002-8728-6691
FU Intramural NIH HHS; NIAID NIH HHS [R21 AI109187]
NR 30
TC 8
Z9 8
U1 1
U2 2
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 JAN
PY 2015
VL 35
IS 1
BP 32
EP 46
DI 10.1007/s10875-014-0106-4
PG 15
WC Immunology
SC Immunology
GA CA3KR
UT WOS:000348805600006
PM 25352053
ER
PT J
AU Swenor, BK
Simonsick, EM
Ferrucci, L
Newman, AB
Rubin, S
Wilson, V
AF Swenor, Bonnielin K.
Simonsick, Eleanor M.
Ferrucci, Luigi
Newman, Anne B.
Rubin, Susan
Wilson, Valerie
CA Hlth Aging Body Composition Study
TI Visual Impairment and Incident Mobility Limitations: The Health, Aging
and Body Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE visual impairment; mobility; physical functioning
ID SALISBURY EYE EVALUATION; OLDER-ADULTS; CONTRAST SENSITIVITY; PHYSICAL
FUNCTION; UNITED-STATES; SEE PROJECT; PERFORMANCE; PREVALENCE;
RELIABILITY; ASSOCIATION
AB ObjectivesTo examine the association between multiple measures of visual impairment (VI) and incident mobility limitations in older adults.
DesignProspective observational cohort study.
SettingMemphis, Tennessee, and Pittsburgh, Pennsylvania.
ParticipantsHealth, Aging and Body Composition study participants aged 70 to 79 without mobility limitations at the Year 3 visit (N=1,862).
MeasurementsVision was measured at the Year 3 visit, and VI was defined as distance visual acuity (VA) worse than 20/40, contrast sensitivity (CS) less than 1.55 log Contrast, and stereoacuity (SA) greater than 85 arcsec. Incident persistent walking and stair climbing limitation was defined as two consecutive 6-month reports of any difficulty walking one-quarter of a mile or walking up 10 steps after 1, 3, and 5years of follow-up.
ResultsAt Year 3 (baseline for these analyses), 7.4% had impaired VA, 27.2% had impaired CS, and 29.2% had impaired SA. At all follow-up times, the incidence of walking and stair climbing limitations was higher in participants with VA, CS, or SA impairment. After 5years, impaired CS and SA were independently associated with greater risk of walking limitation (hazard ratio (HR)(CS)= 1.3, 95% confidence interval (CI)=1.1-1.7; HRSA=1.3, 95% CI=1.1-1.6) and stair climbing limitation (HRCS= 1.4, 95% CI=1.1-1.8; HRSA=1.3, 95% CI=1.1-1.7). Having impaired CS and SA was associated with greater risk of mobility limitations (HRwalking limitations=2.0, 95% CI=1.6-2.5; HRstair limitation= 2.1, 95% CI=1.6-2.8).
ConclusionMultiple aspects of VI may contribute to mobility limitations in older adults. Addressing more than one component of vision may be needed to reduce the effect of vision impairment on functional decline.
C1 [Swenor, Bonnielin K.; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Longitudinal Study Sect, Clin Res Branch, Baltimore, MD 21225 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Pittsburgh, PA USA.
[Rubin, Susan] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Wilson, Valerie] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
RP Swenor, BK (reprint author), NIA, NIH, Harbor Hosp NM 538, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM bonnie.swenor@nih.gov
RI Newman, Anne B./C-6408-2013
OI Newman, Anne B./0000-0002-0106-1150
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050]; National Institute of Nursing
Research Grant [R01-NR012459]; Intramural Research Program of the
National Institutes of Health, NIA
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA Grant
R01-AG028050; and National Institute of Nursing Research Grant
R01-NR012459. This research was supported in part by the Intramural
Research Program of the National Institutes of Health, NIA.
NR 29
TC 7
Z9 7
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2015
VL 63
IS 1
BP 46
EP 54
DI 10.1111/jgs.13183
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AZ7BW
UT WOS:000348374200006
PM 25536849
ER
PT J
AU Lo-Ciganic, WH
Perera, S
Gray, SL
Boudreau, RM
Zgibor, JC
Strotmeyer, ES
Donohue, JM
Bunker, CH
Newman, AB
Simonsick, EM
Bauer, DC
Satterfield, S
Caserotti, P
Harris, T
Shorr, RI
Hanlon, JT
AF Lo-Ciganic, Wei-Hsuan
Perera, Subashan
Gray, Shelly L.
Boudreau, Robert M.
Zgibor, Janice C.
Strotmeyer, Elsa S.
Donohue, Julie M.
Bunker, Clareann H.
Newman, Anne B.
Simonsick, Eleanor M.
Bauer, Douglas C.
Satterfield, Suzanne
Caserotti, Paolo
Harris, Tamara
Shorr, Ronald I.
Hanlon, Joseph T.
CA Hlth Aging Body Composition Study
TI Statin Use and Decline in Gait Speed in Community-Dwelling Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE hydroxymethylglutaryl-CoA reductase inhibitors; statins; gait speed;
physical function; aged
ID PERIPHERAL ARTERIAL-DISEASE; COA REDUCTASE INHIBITORS; PHYSICAL
PERFORMANCE; HEALTH; ATORVASTATIN; CHOLESTEROL; PREDICTOR; SYMPTOMS;
THERAPY; PEOPLE
AB ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults.
DesignLongitudinal cohort study.
SettingHealth, Aging and Body Composition (Health ABC) Study.
ParticipantsTwo thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03.
MeasurementsThe independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care.
ResultsStatin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1m/s or more (adjusted odds ratio (AOR)=0.90, 95% confidence interval (CI)=0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers (AOR=0.78, 95% CI=0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up.
ConclusionThese results suggest that statin use did not increase decline in gait speed in community-dwelling older adults.
C1 [Lo-Ciganic, Wei-Hsuan; Hanlon, Joseph T.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Hlth Policy Inst, Pittsburgh, PA 15261 USA.
[Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Div Geriatr, Dept Med, Sch Med, Pittsburgh, PA 15261 USA.
[Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
[Boudreau, Robert M.; Zgibor, Janice C.; Strotmeyer, Elsa S.; Bunker, Clareann H.; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Simonsick, Eleanor M.; Harris, Tamara] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Sch Med, Div Gen Med, San Francisco, CA USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Caserotti, Paolo] Univ Southern Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Shorr, Ronald I.] North Florida South Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
RP Lo-Ciganic, WH (reprint author), Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, 130 DeSoto St,A636, Pittsburgh, PA 15261 USA.
EM wel32@pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036;
Boudreau, Robert/0000-0003-0162-5187; Donohue, Julie/0000-0003-2418-6017
FU National Institute on Aging [R01-AG 027017, P30-AG024827, T32-AG021885,
K07-AG033174, R01-AG034056, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; National Institute of Nursing Research grants
[R01-NR010135, R01-NR012459]; Agency for Healthcare Research and Quality
grants [R01-HS017695, R01-HS018721]; Intramural Research Program of the
National Institutes of Health, National Institute on Aging
FX This work was supported by National Institute on Aging grants and
contracts (R01-AG 027017, P30-AG024827, T32-AG021885, K07-AG033174,
R01-AG034056, R01-AG028050, N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106), National Institute of Nursing Research grants
(R01-NR010135, R01-NR012459), Agency for Healthcare Research and Quality
grants (R01-HS017695, R01-HS018721), and the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 30
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2015
VL 63
IS 1
BP 124
EP 129
DI 10.1111/jgs.13134
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AZ7BW
UT WOS:000348374200017
PM 25537649
ER
PT J
AU Glynn, NW
Santanasto, AJ
Simonsick, EM
Boudreau, RM
Beach, SR
Schulz, R
Newman, AB
AF Glynn, Nancy W.
Santanasto, Adam J.
Simonsick, Eleanor M.
Boudreau, Robert M.
Beach, Scott R.
Schulz, Richard
Newman, Anne B.
TI The Pittsburgh Fatigability Scale for Older Adults: Development and
Validation
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE fatigue; fatigability; performance measures; validation; mobility
ID BODY-COMPOSITION; FATIGUE; POPULATION; HEALTH; INTERVENTIONS;
ASSOCIATION; MORTALITY; OUTCOMES; FITNESS
AB ObjectivesTo describe the development of the Pittsburgh Fatigability Scale (PFS) and establish its reliability and concurrent and convergent validity against performance measures.
DesignCross-sectional.
SettingUniversity of Pittsburgh, Pittsburgh, Pennsylvania.
ParticipantsScale development sample: 1,013 individuals aged 60 and older from two registries; validation sample: 483 adults aged 60 and older from the Baltimore Longitudinal Study of Aging (BLSA).
MeasurementsThe scale development sample and BLSA participants self-administered an initial 26-item perceived fatigability scale. BLSA participants also completed measures of performance fatigability (perceived exertion from a standard treadmill task and performance deterioration from a fast-paced long-distance corridor walk), a 6-m usual-paced corridor walk, and five timed chair stands.
ResultsPrincipal components analysis with varimax rotation reduced the 26-item scale to the 10-item PFS. The PFS showed strong internal consistency (Cronbach's alpha 0.88) and excellent test-retest reliability (intraclass correlation 0.86). In the validation sample, PFS scores, adjusted for age, sex, and race, were greater for those with high performance fatigability, slow gait speed, worse physical function, and lower fitness, with differences between high and low fatigability ranging from 3.2 to 5.1 points (P<.001).
ConclusionThe 10-item PFS physical fatigability score is a valid and reliable measure of perceived fatigability in older adults and can serve as an adjunct to performance-based fatigability measures for identifying older adults at risk of mobility limitation in clinical and research settings.
C1 [Glynn, Nancy W.; Santanasto, Adam J.; Boudreau, Robert M.; Newman, Anne B.] Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Beach, Scott R.; Schulz, Richard] Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA 15261 USA.
[Schulz, Richard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA.
RP Glynn, NW (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 DeSoto St,A531 Crabtree Hall, Pittsburgh, PA 15261 USA.
EM glynnn@edc.pitt.edu
RI Newman, Anne B./C-6408-2013;
OI Newman, Anne B./0000-0002-0106-1150; Boudreau,
Robert/0000-0003-0162-5187; Glynn, Nancy/0000-0003-2265-0162
FU Pittsburgh Claude D. Pepper Older Americans Independence Center
Developmental Pilot Grant [NIH P30 AG024826]; Intramural Research
Program, National Institute on Aging
FX This research was funded by Pittsburgh Claude D. Pepper Older Americans
Independence Center Developmental Pilot Grant NIH P30 AG024826 and the
Intramural Research Program, National Institute on Aging.
NR 25
TC 9
Z9 9
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2015
VL 63
IS 1
BP 130
EP 135
DI 10.1111/jgs.13191
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AZ7BW
UT WOS:000348374200018
PM 25556993
ER
PT J
AU Schonberg, MA
Breslau, ES
AF Schonberg, Mara A.
Breslau, Erica S.
TI Mammography Screening for Women Aged 70 and Older: At a Crossroads
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Editorial Material
ID BREAST-CANCER INCIDENCE; FOLLOW-UP; SURVIVAL; COMORBIDITY; DIAGNOSIS;
OUTCOMES; TIME
C1 [Schonberg, Mara A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care,Dept Med, Boston, MA 02215 USA.
[Breslau, Erica S.] NCI, Proc Care Res Branch, Behav Res Program, NIH, Bethesda, MD 20892 USA.
RP Schonberg, MA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gen Med & Primary Care,Dept Med, Boston, MA 02215 USA.
FU NCI NIH HHS [R01 CA181357]
NR 19
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JAN
PY 2015
VL 63
IS 1
BP 170
EP 172
DI 10.1111/jgs.13189
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AZ7BW
UT WOS:000348374200024
PM 25597565
ER
PT J
AU Gale, PJ
Yergey, AL
Duncan, MW
Yu, K
AF Gale, P. Jane
Yergey, Alfred L.
Duncan, Mark W.
Yu, Kate
TI Quantifying Small Molecules by Mass Spectrometry
SO LC GC NORTH AMERICA
LA English
DT Article
C1 [Gale, P. Jane] RCA Labs, New York, NY USA.
[Gale, P. Jane] Bristol Myers Squibb Co, New York, NY 10154 USA.
[Duncan, Mark W.] Biodesix Inc, Boulder, CO USA.
[Yergey, Alfred L.] Rice Univ, Dept Chem, Houston, TX 77251 USA.
[Yergey, Alfred L.] NICHD, NIH, Rockville, MD USA.
[Yergey, Alfred L.] Sect Metab Anal & Mass Spectrometry, Bethesda, MD USA.
[Yergey, Alfred L.] Inst Mass Spectrometry Facility, Bethesda, MD USA.
RP Yu, K (reprint author), LC MS Technol, St Louis, MO 63122 USA.
EM lcgcedit@lcgcmag.com
NR 6
TC 0
Z9 0
U1 4
U2 8
PU ADVANSTAR COMMUNICATIONS INC
PI DULUTH
PA 131 W 1ST STREET, DULUTH, MN 55802 USA
SN 1527-5949
EI 1939-1889
J9 LC GC N AM
JI LC GC N. AM.
PD JAN
PY 2015
VL 33
IS 1
BP 34
EP 41
PG 8
WC Chemistry, Analytical
SC Chemistry
GA CA0XL
UT WOS:000348636700005
ER
PT J
AU Milenic, DE
Baidoo, KE
Kim, YS
Brechbiel, MW
AF Milenic, Diane E.
Baidoo, Kwamena E.
Kim, Young-Seung
Brechbiel, Martin W.
TI Evaluation of cetuximab as a candidate for targeted alpha-particle
radiation therapy of HER1-positive disseminated intraperitoneal disease
SO MABS
LA English
DT Article
DE radioimmunotherapy; -particle; Pb-212; cetuximab; HER1; mAb; monoclonal
antibody; RIT; radioimmunotherapy; EGFR; epidermal growth factor
receptor; HulgG; human immunoglobulin; TCMC; 1; 4; 7; 10-tetraaza-1; 4;
7; 10-tetra-(2-carbamoyl methyl)-cyclododecane; BSA; bovine serum
albumin; %ID; g; percent injected dose per gram; i; p; intraperitoneal;
s; c; subcutaneous; PBS; phosphate-buffered saline; PET; positron
emission tomography; MS; median survival
ID GROWTH-FACTOR RECEPTOR; DISSEMINATED PERITONEAL DISEASE; SQUAMOUS-CELL
CARCINOMA; ANTI-EGFR-ANTIBODY; MONOCLONAL-ANTIBODY; PROSTATE-CANCER;
IN-VITRO; COLORECTAL-CANCER; SPECTROPHOTOMETRIC METHOD; PRECLINICAL
EVALUATION
AB Although the epidermal growth factor receptor (EGFR), also known as HER1, has been studied for over a decade, it continues to be a molecule of great interest and focus of investigators for development of targeted therapies. The marketed monoclonal antibody cetuximab binds to HER1, and thus might serve as the basis for creation of imaging or therapies that target this receptor. The potential of cetuximab as a vehicle for the delivery of -particle radiation was investigated in an intraperitoneal tumor mouse model. The effective working dose of 10Ci of Pb-212-cetuximab was determined from a dose (10-50Ci) escalation study. Toxicity, as indicated by the lack of animal weight loss, was not evident at the 10Ci dose of Pb-212-cetuximab. A subsequent study demonstrated Pb-212-cetuximab had a therapeutic efficacy similar to that of Pb-212-trastuzumab (p = 0.588). Gemcitabine given 24h prior to Pb-212-cetuximab increased the median survival from 174 d to 283 d, but carboplatin suppressed the effectiveness of Pb-212-cetuximab. Notably, concurrent treatment of tumor-bearing mice with Pb-212-labeled cetuximab and trastuzumab provided therapeutic benefit that was greater than either antibody alone. In conclusion, cetuximab proved to be an effective vehicle for targeting HER1-expressing tumors with -radiation for the treatment of disseminated intraperitoneal disease. These studies provide further evidence that the multimodality therapy regimens may have greater efficacy and benefit in the treatment of cancer patients.
C1 [Milenic, Diane E.; Baidoo, Kwamena E.; Kim, Young-Seung; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Milenic, DE (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM milenicd@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 57
TC 5
Z9 5
U1 2
U2 11
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1942-0862
EI 1942-0870
J9 MABS-AUSTIN
JI mAbs
PD JAN-FEB
PY 2015
VL 7
IS 1
BP 255
EP 264
DI 10.4161/19420862.2014.985160
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AZ8KC
UT WOS:000348463300024
PM 25587678
ER
PT J
AU Donninger, H
Clark, J
Rinaldo, F
Nelson, N
Barnoud, T
Schmidt, ML
Hobbing, KR
Vos, MD
Sils, B
Clark, GJ
AF Donninger, Howard
Clark, Jennifer
Rinaldo, Francesca
Nelson, Nicholas
Barnoud, Thibaut
Schmidt, M. Lee
Hobbing, Katharine R.
Vos, Michele D.
Sils, Brian
Clark, Geoffrey J.
TI The RASSF1A Tumor Suppressor Regulates XPA-Mediated DNA Repair
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-A; REPLICATION PROTEIN-A;
XERODERMA-PIGMENTOSUM; KNOCKOUT MICE; RAS; PATHWAY; CANCER; DAMAGE;
ASSOCIATION
AB RASSF1A may be the most frequently inactivated tumor suppressor identified in human cancer so far. It is a proapoptotic Ras effector and plays an important role in the apoptotic DNA damage response (DDR). We now show that in addition to DDR regulation, RASSF1A also plays a key role in the DNA repair process itself. We show that RASSF1A forms a DNA damage-regulated complex with the key DNA repair protein xeroderma pigmentosum A (XPA). XPA requires RASSF1A to exert full repair activity, and RASSF1A-deficient cells exhibit an impaired ability to repair DNA. Moreover, a cancer-associated RASSF1A single-nucleotide polymorphism (SNP) variant exhibits differential XPA binding and inhibits DNA repair. The interaction of XPA with other components of the repair complex, such as replication protein A (RPA), is controlled in part by a dynamic acetylation/deacetylation cycle. We found that RASSF1A and its SNP variant differentially regulate XPA protein acetylation, and the SNP variant hyperstabilizes the XPA-RPA70 complex. Thus, we identify two novel functions for RASSF1A in the control of DNA repair and protein acetylation. As RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage.
C1 [Donninger, Howard; Clark, Jennifer; Rinaldo, Francesca] Univ Louisville, JG Brown Canc Ctr, Dept Med, Mol Targets Program, Louisville, KY 40292 USA.
[Nelson, Nicholas; Barnoud, Thibaut; Schmidt, M. Lee] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA.
[Hobbing, Katharine R.; Sils, Brian; Clark, Geoffrey J.] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
[Vos, Michele D.] NCI, NIH, Bethesda, MD 20892 USA.
RP Clark, GJ (reprint author), Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA.
EM gjclar01@louisville.edu
FU NCI intramural funds; [1P20 RR18733]; [NIH R01 CA133171]
FX The work was supported by awards 1P20 RR18733, NIH R01 CA133171, and NCI
intramural funds (G.J.C.).
NR 53
TC 8
Z9 8
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JAN
PY 2015
VL 35
IS 1
BP 277
EP 287
DI 10.1128/MCB.00202-14
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CB0CL
UT WOS:000349292400022
PM 25368379
ER
PT J
AU Paul, E
Zhu, ZI
Landsman, D
Morse, RH
AF Paul, Emily
Zhu, Z. Iris
Landsman, David
Morse, Randall H.
TI Genome-Wide Association of Mediator and RNA Polymerase II in Wild-Type
and Mediator Mutant Yeast
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; IN-VIVO; TRANSCRIPTIONAL ACTIVATION;
CONTAINING GENES; COMPLEX; EXPRESSION; PROMOTER; BINDING; PROTEIN;
MODULE
AB Mediator is a large, multisubunit complex that is required for essentially all mRNA transcription in eukaryotes. In spite of the importance of Mediator, the range of its targets and how it is recruited to these is not well understood. Previous work showed that in Saccharomyces cerevisiae, Mediator contributes to transcriptional activation by two distinct mechanisms, one depending on the tail module triad and favoring SAGA-regulated genes, and the second occurring independently of the tail module and favoring TFIID-regulated genes. Here, we use chromatin immunoprecipitation sequencing (ChIP-seq) to show that dependence on tail module subunits for Mediator recruitment and polymerase II (Pol II) association occurs preferentially at SAGA-regulated over TFIID-regulated genes on a genome-wide scale. We also show that recruitment of tail module subunits to active gene promoters continues genome-wide when Mediator integrity is compromised in med17 temperature-sensitive (ts) yeast, demonstrating the modular nature of the Mediator complex in vivo. In addition, our data indicate that promoters exhibiting strong and stable occupancy by Mediator have a wide range of activity and are enriched for targets of the Tup1-Cyc8 repressor complex. We also identify a number of strong Mediator occupancy peaks that overlap dubious open reading frames (ORFs) and are likely to include previously unrecognized upstream activator sequences.
C1 [Paul, Emily; Morse, Randall H.] New York State Dept Hlth, Wadsworth Ctr, Mol Genet Lab, Albany, NY USA.
[Morse, Randall H.] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY USA.
[Zhu, Z. Iris; Landsman, David] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Landsman, D (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM landsman@ncbi.nlm.nih.gov; randall.morse@health.ny.gov
OI Morse, Randall/0000-0003-0000-8718; Landsman, David/0000-0002-9819-6675
FU NSF [MCB0949722]; Wadsworth Center; Intramural Research Program of the
NIH, NLM, NCBI
FX This work was supported by funding from the NSF (MCB0949722 to R. H.
M.), the Wadsworth Center, and the Intramural Research Program of the
NIH, NLM, NCBI.
NR 48
TC 10
Z9 10
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JAN
PY 2015
VL 35
IS 1
BP 331
EP 342
DI 10.1128/MCB.00991-14
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CB0CL
UT WOS:000349292400026
PM 25368384
ER
PT J
AU Agarwal, S
Macfarlan, TS
Sartor, MA
Iwase, S
AF Agarwal, Saurabh
Macfarlan, Todd S.
Sartor, Maureen A.
Iwase, Shigeki
TI Sequencing of first-strand cDNA library reveals full-length
transcriptomes
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ANALYSIS; MULTIPLEX RNA-SEQ; ESCHERICHIA-COLI; ALTERNATIVE
POLYADENYLATION; DIVERGENT TRANSCRIPTION; MAMMALIAN PROMOTERS;
EXPRESSION ANALYSIS; ACTIVE PROMOTERS; SINGLE CELLS; POLYMERASE
AB Massively parallel strand-specific sequencing of RNA (ssRNA-seq) has emerged as a powerful tool for profiling complex transcriptomes. However, many current methods for ssRNA-seq suffer from the underrepresentation of both the 5' and 3' ends of RNAs, which can be attributed to second-strand cDNA synthesis. The 5' and 3' ends of RNA harbour crucial information for gene regulation; namely, transcription start sites (TSSs) and polyadenylation sites. Here we report a novel ssRNA-seq method that does not involve second-strand cDNA synthesis, as we Directly Ligate sequencing Adaptors to the First-strand cDNA (DLAF). This novel method with fewer enzymatic reactions results in a higher quality of the libraries than the conventional method. Sequencing of DLAF libraries followed by a novel analysis pipeline enables the profiling of both 5' ends and polyadenylation sites at near-base resolution. Therefore, DLAF offers the first genomics tool to obtain the 'full-length' transcriptome with a single library.
C1 [Agarwal, Saurabh; Iwase, Shigeki] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Macfarlan, Todd S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Sartor, Maureen A.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
RP Iwase, S (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
EM siwase@umich.edu
FU University of Michigan Medical School; Cooley's Anemia Foundation
Fellowship; LICR; California Institute for Regenerative Medicine
[RN2-00905]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development DIR [HD008933]
FX We thank Dr Bing Ren at the Ludwig Institute for Cancer Research (LICR),
San Diego, for helpful discussions and sequencing of the libraries. We
also thank Dr Gary Hon at the LICR, San Diego, for helpful discussions
and guidance with bioinformatics. We are grateful to Drs Jacob L.
Mueller and John Kim in the Department of Human Genetics at the
University of Michigan for their critical readings and suggestions for
the manuscript. The work was supported by grants from the University of
Michigan Medical School (to S.I.), Cooley's Anemia Foundation Fellowship
(to S.I.), the LICR (to B.R.), the California Institute for Regenerative
Medicine (RN2-00905 to B.R.) and the Eunice Kennedy Shriver National
Institute of Child Health and Human Development DIR (HD008933 to
T.S.M.).
NR 57
TC 2
Z9 2
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 6002
DI 10.1038/ncomms7002
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3NB
UT WOS:000348812400003
PM 25607527
ER
PT J
AU Igartua, C
Myers, RA
Mathias, RA
Pino-Yanes, M
Eng, C
Graves, PE
Levin, AM
Del-Rio-Navarro, BE
Jackson, DJ
Livne, OE
Rafaels, N
Edlund, CK
Yang, JJ
Huntsman, S
Salam, MT
Romieu, I
Mourad, R
Gern, JE
Lemanske, RF
Wyss, A
Hoppin, JA
Barnes, KC
Burchard, EG
Gauderman, WJ
Martinez, FD
Raby, BA
Weiss, ST
Williams, LK
London, SJ
Gilliland, FD
Nicolae, DL
Ober, C
AF Igartua, Catherine
Myers, Rachel A.
Mathias, Rasika A.
Pino-Yanes, Maria
Eng, Celeste
Graves, Penelope E.
Levin, Albert M.
Del-Rio-Navarro, Blanca E.
Jackson, Daniel J.
Livne, Oren E.
Rafaels, Nicholas
Edlund, Christopher K.
Yang, James J.
Huntsman, Scott
Salam, Muhammad T.
Romieu, Isabelle
Mourad, Raphael
Gern, James E.
Lemanske, Robert F.
Wyss, Annah
Hoppin, Jane A.
Barnes, Kathleen C.
Burchard, Esteban G.
Gauderman, W. James
Martinez, Fernando D.
Raby, Benjamin A.
Weiss, Scott T.
Williams, L. Keoki
London, Stephanie J.
Gilliland, Frank D.
Nicolae, Dan L.
Ober, Carole
TI Ethnic-specific associations of rare and low-frequency DNA sequence
variants with asthma
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MTHFR C677T POLYMORPHISM; MISSING HERITABILITY;
LOCI; METAANALYSIS; POPULATION; EXPRESSION; GENES; RISK; DISEASE
AB Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1-5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case-parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample (P = 4.31 x 10(-6); OR = 1.25; MAF = 1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12-21 asthma locus in the Latino and combined samples (P = 7.81 x 10(-8) and 4.09 x 10(-8), respectively) and MTHFR in the African ancestry sample (P = 1.72 x 10(-6)). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the 'missing heritability' of asthma.
C1 [Igartua, Catherine; Myers, Rachel A.; Livne, Oren E.; Mourad, Raphael; Nicolae, Dan L.; Ober, Carole] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Mathias, Rasika A.; Barnes, Kathleen C.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA.
[Pino-Yanes, Maria; Eng, Celeste; Huntsman, Scott; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Pino-Yanes, Maria] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid 28029, Spain.
[Graves, Penelope E.; Martinez, Fernando D.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ 85721 USA.
[Graves, Penelope E.; Martinez, Fernando D.] Univ Arizona, Inst BIO5, Tucson, AZ 85721 USA.
[Levin, Albert M.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
[Del-Rio-Navarro, Blanca E.] Hosp Infantil Mexico Dr Federico Gomez, Mexico City 06720, DF, Mexico.
[Jackson, Daniel J.; Gern, James E.; Lemanske, Robert F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI 53726 USA.
[Rafaels, Nicholas] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21224 USA.
[Edlund, Christopher K.; Salam, Muhammad T.; Gauderman, W. James; Gilliland, Frank D.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Yang, James J.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48202 USA.
[Romieu, Isabelle] Int Agcy Res Canc, F-69372 Lyon, France.
[Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Internal Med, Madison, WI 53726 USA.
[Lemanske, Robert F.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53726 USA.
[Wyss, Annah; Hoppin, Jane A.; London, Stephanie J.] NIEHS, Div Intramural Res, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
[Hoppin, Jane A.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27607 USA.
[Burchard, Esteban G.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Raby, Benjamin A.; Weiss, Scott T.] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA USA.
[Raby, Benjamin A.] Harvard Univ, Sch Med, Div Pulm & Crit Care Med, Boston, MA USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI 48202 USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI 48202 USA.
[Nicolae, Dan L.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Nicolae, Dan L.] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
RP Ober, C (reprint author), Univ Chicago, Dept Human Genet, 920 East 58th St,CLSC 425, Chicago, IL 60637 USA.
EM c-ober@bsd.uchicago.edu
RI Pino-Yanes, Maria/C-8498-2017;
OI Pino-Yanes, Maria/0000-0003-0332-437X; London,
Stephanie/0000-0003-4911-5290
FU NIH [RC2 HL10165, P30 ES007048, P01 ES009581, P0 1ES01162, R01 HL118267,
R01 AI079139]; Intramural Research Program of the NIH (NIEHS) [Z01
CP010119, Z01 ES049030, ES102385]; American Asthma Foundation; Hastings
Foundation; Fund for Henry Ford Hospital; Computation Institute;
Biological Sciences Division of the University of Chicago; Argonne
National Laboratory [S10 RR029030-01]; Northwest Genomics Center at the
University of Washington, Department of Genome Sciences, under US
Federal Government from the National Heart, Lung and Blood Institute
[HHSN268201100037C]; Molecular Genomics Core at the University of
Southern California [P30ES007048, P01ES009581]; Center for Inherited
Disease Research at Johns Hopkins University; Fundacion Ramon Areces;
National Institutes of Health [T32 GM007197]; Ruth L. Kirschstein
National Research Service Award [PA-11-112]; Mary Beryl Patch Turnbull
Scholar Program
FX This work was supported by NIH grants RC2 HL10165, P30 ES007048, P01
ES009581, P0 1ES01162, R01 HL118267 and R01 AI079139, the Intramural
Research Program of the NIH (NIEHS Z01 CP010119, Z01 ES049030 and
ES102385), the American Asthma Foundation, the Hastings Foundation, the
Fund for Henry Ford Hospital and through resources provided by the
Computation Institute and the Biological Sciences Division of the
University of Chicago and Argonne National Laboratory (S10 RR029030-01).
Genotyping services were provided by the Northwest Genomics Center at
the University of Washington, Department of Genome Sciences, under US
Federal Government contract number HHSN268201100037C from the National
Heart, Lung and Blood Institute, and the Molecular Genomics Core at the
University of Southern California (P30ES007048 and P01ES009581) and the
Center for Inherited Disease Research at Johns Hopkins University.
M.P.-Y. was funded by a Postdoctoral Fellowship from Fundacion Ramon
Areces. C.I. was supported by National Institutes of Health Grant T32
GM007197 and by the Ruth L. Kirschstein National Research Service Award
(PA-11-112). KCB was supported in part by the Mary Beryl Patch Turnbull
Scholar Program.
NR 46
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 5965
DI 10.1038/ncomms6965
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3MO
UT WOS:000348811100009
PM 25591454
ER
PT J
AU Kucuk, C
Jiang, B
Hu, XZ
Zhang, WY
Chan, JKC
Xiao, WM
Lack, N
Alkan, C
Williams, JC
Avery, KN
Kavak, P
Scuto, A
Sen, E
Gaulard, P
Staudt, L
Iqbal, J
Zhang, WW
Cornish, A
Gong, Q
Yang, QP
Sun, H
d'Amore, F
Leppa, S
Liu, WP
Fu, K
de Leval, L
McKeithan, T
Chan, WC
AF Kucuk, Can
Jiang, Bei
Hu, Xiaozhou
Zhang, Wenyan
Chan, John K. C.
Xiao, Wenming
Lack, Nathan
Alkan, Can
Williams, John C.
Avery, Kendra N.
Kavak, Pinar
Scuto, Anna
Sen, Emel
Gaulard, Philippe
Staudt, Lou
Iqbal, Javeed
Zhang, Weiwei
Cornish, Adam
Gong, Qiang
Yang, Qunpei
Sun, Hong
d'Amore, Francesco
Leppa, Sirpa
Liu, Weiping
Fu, Kai
de Leval, Laurence
McKeithan, Timothy
Chan, Wing C.
TI Activating mutations of STAT5B and STAT3 in lymphomas derived from gamma
delta-T or NK cells
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GRANULAR LYMPHOCYTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENE; SEQUENCING DATA;
EXPRESSION; MALIGNANCIES; NEOPLASMS; FREQUENT; PATHOGENESIS; DISORDERS;
LANDSCAPE
AB Lymphomas arising from NK or gamma delta-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n - 51), gamma delta-T-cell lymphomas (n - 43) and their cell lines (n = 9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of gamma delta-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy.
C1 [Kucuk, Can; Jiang, Bei; Hu, Xiaozhou; Scuto, Anna; McKeithan, Timothy; Chan, Wing C.] City Hope Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Zhang, Wenyan; Yang, Qunpei; Sun, Hong; Liu, Weiping; Fu, Kai] Sichuan Univ, West China Hosp, Dept Pathol, Chengdu 610041, Peoples R China.
[Chan, John K. C.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Xiao, Wenming] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Rockville, MD 20857 USA.
[Lack, Nathan; Sen, Emel] Koc Univ, Dept Pharmacol, TR-34450 Istanbul, Turkey.
[Alkan, Can] Bilkent Univ, Dept Comp Engn, TR-06800 Ankara, Turkey.
[Williams, John C.; Avery, Kendra N.] Beckman Res Inst City Hope, Dept Mol Med, Duarte, CA 91010 USA.
[Kavak, Pinar] Bogazici Univ, Dept Comp Engn, TR-34342 Istanbul, Turkey.
[Gaulard, Philippe] Univ Paris Est, INSERM, U955, Dept Pathol,Grp Henri Mondor Albert Chenevier, F-94000 Creteil, France.
[Staudt, Lou] NCI, Ctr Canc Res, Mol Biol Lymphoid Malignancies Sect, Bethesda, MD 20892 USA.
[Iqbal, Javeed; Zhang, Weiwei] Univ Nebraska, Ctr Med, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
[Cornish, Adam] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA.
[Gong, Qiang] Chinese Acad Sci, Beijing Inst Genom, Beijing 100029, Peoples R China.
[d'Amore, Francesco] Aarhus Univ Hosp, Dept Hematol, DK-8000 Aarhus, Denmark.
[Leppa, Sirpa] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki 00029, Finland.
[de Leval, Laurence] Univ Pathol, Pathol Clin Inst, CH-1011 Lausanne, Switzerland.
RP Chan, WC (reprint author), City Hope Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
EM jochan@coh.org
RI Alkan, Can/D-2982-2009; Kucuk, Can/K-3913-2015;
OI Alkan, Can/0000-0002-5443-0706; Kucuk, Can/0000-0001-5540-9012;
McKeithan, Timothy/0000-0003-2242-3074; Leppa, Sirpa/0000-0002-8265-511X
NR 44
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U1 8
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 6025
DI 10.1038/ncomms7025
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3TP
UT WOS:000348829800003
PM 25586472
ER
PT J
AU Petkov, CI
Kikuchi, Y
Milne, AE
Mishkin, M
Rauschecker, JP
Logothetis, NK
AF Petkov, Christopher I.
Kikuchi, Yukiko
Milne, Alice E.
Mishkin, Mortimer
Rauschecker, Josef P.
Logothetis, Nikos K.
TI Different forms of effective connectivity in primate frontotemporal
pathways
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SUPERIOR TEMPORAL SULCUS; PARABELT AUDITORY-CORTEX; PREFRONTAL CORTEX;
RHESUS-MONKEY; ELECTRICAL MICROSTIMULATION; MACAQUE MONKEYS;
FRONTAL-CORTEX; FUNCTIONAL NETWORK; CEREBRAL-CORTEX; COMPLEX SOUNDS
AB It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.
C1 [Petkov, Christopher I.; Kikuchi, Yukiko; Milne, Alice E.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
[Petkov, Christopher I.; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany.
[Kikuchi, Yukiko; Mishkin, Mortimer] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Kikuchi, Yukiko; Rauschecker, Josef P.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA.
[Logothetis, Nikos K.] Univ Manchester, Div Imaging Sci & Biomed Engn, Manchester M13 9PT, Lancs, England.
[Rauschecker, Josef P.] Tech Univ Munich, Inst Adv Study, D-85748 Garching, Germany.
RP Petkov, CI (reprint author), Newcastle Univ, Inst Neurosci, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England.
EM chris.petkov@ncl.ac.uk
RI Petkov, Christopher/O-5318-2015
OI Petkov, Christopher/0000-0002-4932-7907
FU Max Planck Society; Alexander von Humboldt Foundation; Wellcome Trust
Investigator Award [WT102961MA]; NSF [PIRE OISE-0730255]; NIMH, NIH;
[NIH-R01DC003489]; [NIH-R56NS052494]
FX We thank M. Augath for MRI experimental support and R. Saunders and D.
Yu for invaluable assistance with histological processing. T. Griffiths,
M. Kaiser, L. Orton, C. Perrodin, A. Rees, L. Romanski, K. Saleem, B.
Scott and B. Wilson provided helpful comments on or discussion of the
manuscript. Support provided by Max Planck Society (N.K.L.); Alexander
von Humboldt Foundation (C.I.P.); Wellcome Trust Investigator Award
WT102961MA (C.I.P.); NIH-R01DC003489 (J.P.R.), NIH-R56NS052494 (J.P.R.);
NSF PIRE OISE-0730255 (J.P.R.); NIMH, NIH (M.M.).
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U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 6000
DI 10.1038/ncomms7000
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3NB
UT WOS:000348812400001
PM 25613079
ER
PT J
AU Venditti, V
Tugarinov, V
Schwieters, CD
Grishaev, A
Clore, GM
AF Venditti, Vincenzo
Tugarinov, Vitali
Schwieters, Charles D.
Grishaev, Alexander
Clore, G. Marius
TI Large interdomain rearrangement triggered by suppression of micro- to
millisecond dynamics in bacterial Enzyme I
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SUGAR PHOSPHOTRANSFERASE SYSTEM; MOLECULAR-WEIGHT PROTEINS; N-TERMINAL
DOMAIN; X-RAY-SCATTERING; ESCHERICHIA-COLI; NMR-SPECTROSCOPY;
SUBSTRATE-BINDING; BIOLOGICAL MACROMOLECULES; ALPHA-KETOGLUTARATE;
CHEMICAL-EXCHANGE
AB Enzyme I (EI), the first component of the bacterial phosphotransfer signal transduction system, undergoes one of the largest substrate-induced interdomain rearrangements documented to date. Here we characterize the perturbations generated by two small molecules, the natural substrate phosphoenolpyruvate and the inhibitor alpha-ketoglutarate, on the structure and dynamics of EI using NMR, small-angle X-ray scattering and biochemical techniques. The results indicate unambiguously that the open-to-closed conformational switch of EI is triggered by complete suppression of micro-to millisecond dynamics within the C-terminal domain of EI. Indeed, we show that a ligand-induced transition from a dynamic to a more rigid conformational state of the C-terminal domain stabilizes the interface between the N- and C-terminal domains observed in the structure of the closed state, thereby promoting the resulting conformational switch and autophosphorylation of EI. The mechanisms described here may be common to several other multidomain proteins and allosteric systems.
C1 [Venditti, Vincenzo; Tugarinov, Vitali; Grishaev, Alexander; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
FU US Department of Energy [W-31-109-ENG-38]; NCI [PUP-77]; NIH [PUP-77];
Argonne National Laboratory; NIH Intramural Programs of NIDDK; CIT;
Intramural AIDS Targeted Antiviral Program of the Office of the Director
of the NIH
FX We thank S. Seifert and X. Zuo for assistance with SAXS data collection
and gratefully acknowledge use of the Advanced Photon Source, supported
by the US Department of Energy, contract no. W-31-109-ENG-38, and the
shared scattering beamline resource allocated under the PUP-77 agreement
between NCI, NIH and the Argonne National Laboratory. This work was
supported by funds from the NIH Intramural Programs of NIDDK (to G.M.C.)
and CIT (to C.D.S.) and from the Intramural AIDS Targeted Antiviral
Program of the Office of the Director of the NIH (to G.M.C.).
NR 43
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U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 5960
DI 10.1038/ncomms6960
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3MO
UT WOS:000348811100004
PM 25581904
ER
PT J
AU Wessel, J
Chu, AY
Willems, SM
Wang, S
Yaghootkar, H
Brody, JA
Dauriz, M
Hivert, MF
Raghavan, S
Lipovich, L
Hidalgo, B
Fox, K
Huffman, JE
An, P
Lu, YC
Rasmussen-Torvik, LJ
Grarup, N
Ehm, MG
Li, L
Baldridge, AS
Stancakova, A
Abrol, R
Besse, CL
Boland, A
Bork-Jensen, J
Fornage, M
Freitag, DF
Garcia, ME
Guo, XQ
Hara, K
Isaacs, A
Jakobsdottir, J
Lange, LA
Layton, JC
Li, M
Zhao, JH
Meidtner, K
Morrison, AC
Nalls, MA
Peters, MJ
Sabater-Lleal, M
Schurmann, C
Silveira, A
Smith, AV
Southam, L
Stoiber, MH
Strawbridge, RJ
Taylor, KD
Varga, TV
Allin, KH
Amin, N
Aponte, JL
Aung, T
Barbieri, C
Bihlmeyer, NA
Boehnke, M
Bombieri, C
Bowden, DW
Burns, SM
Chen, YN
Chen, YD
Cheng, CY
Correa, A
Czajkowski, J
Dehghan, A
Ehret, GB
Eiriksdottir, G
Escher, SA
Farmaki, AE
Franberg, M
Gambaro, G
Giulianini, F
Goddard, WA
Goel, A
Gottesman, O
Grove, ML
Gustafsson, S
Hai, Y
Hallmans, G
Heo, J
Hoffmann, P
Ikram, MK
Jensen, RA
Jorgensen, ME
Jorgensen, T
Karaleftheri, M
Khor, CC
Kirkpatrick, A
Kraja, AT
Kuusisto, J
Lange, EM
Lee, IT
Lee, WJ
Leong, A
Liao, JM
Liu, CY
Liu, YM
Lindgren, CM
Linneberg, A
Malerba, G
Mamakou, V
Marouli, E
Maruthur, NM
Matchan, A
McKean-Cowdin, R
McLeod, O
Metcalf, GA
Mohlke, KL
Muzny, DM
Ntalla, I
Palmer, ND
Pasko, D
Peter, A
Rayner, NW
Renstrom, F
Rice, K
Sala, CF
Sennblad, B
Serafetinidis, I
Smith, JA
Soranzo, N
Speliotes, EK
Stahl, EA
Stirrups, K
Tentolouris, N
Thanopoulou, A
Torres, M
Traglia, M
Tsafantakis, E
Javad, S
Yanek, LR
Zengini, E
Becker, DM
Bis, JC
Brown, JB
Cupples, LA
Hansen, T
Ingelsson, E
Karter, AJ
Lorenzo, C
Mathias, RA
Norris, JM
Peloso, GM
Sheu, WHH
Toniolo, D
Vaidya, D
Varma, R
Wagenknecht, LE
Boeing, H
Bottinger, EP
Dedoussis, G
Deloukas, P
Ferrannini, E
Franco, OH
Franks, PW
Gibbs, RA
Gudnason, V
Hamsten, A
Harris, TB
Hattersley, AT
Hayward, C
Hofman, A
Jansson, JH
Langenberg, C
Launer, LJ
Levy, D
Oostra, BA
O'Donnell, CJ
O'Rahilly, S
Padmanabhan, S
Pankow, JS
Polasek, O
Province, MA
Rich, SS
Ridker, PM
Rudan, I
Schulze, MB
Smith, BH
Uitterlinden, AG
Walker, M
Watkins, H
Wong, TY
Zeggini, E
Laakso, M
Borecki, IB
Chasman, DI
Pedersen, O
Psaty, BM
Tai, ES
van Duijn, CM
Wareham, NJ
Waterworth, DM
Boerwinkle, E
Kao, WHL
Florez, JC
Loos, RJF
Wilson, JG
Frayling, TM
Siscovick, DS
Dupuis, J
Rotter, JI
Meigs, JB
Scott, RA
Goodarzi, MO
Sharp, SJ
Forouhi, NG
Kerrison, ND
Lucarelli, DM
Sims, M
Barroso, I
McCarthy, MI
Arriola, L
Balkau, B
Barricarte, A
Gonzalez, C
Grioni, S
Kaaks, R
Key, TJ
Navarro, C
Nilsson, PM
Overvad, K
Palli, D
Panico, S
Quiros, JR
Rolandsson, O
Sacerdote, C
Sanchez, MJ
Slimani, N
Tjonneland, A
Tumino, R
van der A, DL
van der Schouw, YT
Riboli, E
AF Wessel, Jennifer
Chu, Audrey Y.
Willems, Sara M.
Wang, Shuai
Yaghootkar, Hanieh
Brody, Jennifer A.
Dauriz, Marco
Hivert, Marie-France
Raghavan, Sridharan
Lipovich, Leonard
Hidalgo, Bertha
Fox, Keolu
Huffman, Jennifer E.
An, Ping
Lu, Yingchang
Rasmussen-Torvik, Laura J.
Grarup, Niels
Ehm, Margaret G.
Li, Li
Baldridge, Abigail S.
Stancakova, Alena
Abrol, Ravinder
Besse, Celine
Boland, Anne
Bork-Jensen, Jette
Fornage, Myriam
Freitag, Daniel F.
Garcia, Melissa E.
Guo, Xiuqing
Hara, Kazuo
Isaacs, Aaron
Jakobsdottir, Johanna
Lange, Leslie A.
Layton, Jill C.
Li, Man
Zhao, Jing Hua
Meidtner, Karina
Morrison, Alanna C.
Nalls, Mike A.
Peters, Marjolein J.
Sabater-Lleal, Maria
Schurmann, Claudia
Silveira, Angela
Smith, Albert V.
Southam, Lorraine
Stoiber, Marcus H.
Strawbridge, Rona J.
Taylor, Kent D.
Varga, Tibor V.
Allin, Kristine H.
Amin, Najaf
Aponte, Jennifer L.
Aung, Tin
Barbieri, Caterina
Bihlmeyer, Nathan A.
Boehnke, Michael
Bombieri, Cristina
Bowden, Donald W.
Burns, Sean M.
Chen, Yuning
Chen, Yii-Deri
Cheng, Ching-Yu
Correa, Adolfo
Czajkowski, Jacek
Dehghan, Abbas
Ehret, Georg B.
Eiriksdottir, Gudny
Escher, Stefan A.
Farmaki, Aliki-Eleni
Franberg, Mattias
Gambaro, Giovanni
Giulianini, Franco
Goddard, William A., III
Goel, Anuj
Gottesman, Omri
Grove, Megan L.
Gustafsson, Stefan
Hai, Yang
Hallmans, Goeran
Heo, Jiyoung
Hoffmann, Per
Ikram, Mohammad K.
Jensen, Richard A.
Jorgensen, Marit E.
Jorgensen, Torben
Karaleftheri, Maria
Khor, Chiea C.
Kirkpatrick, Andrea
Kraja, Aldi T.
Kuusisto, Johanna
Lange, Ethan M.
Lee, I. T.
Lee, Wen-Jane
Leong, Aaron
Liao, Jiemin
Liu, Chunyu
Liu, Yongmei
Lindgren, Cecilia M.
Linneberg, Allan
Malerba, Giovanni
Mamakou, Vasiliki
Marouli, Eirini
Maruthur, Nisa M.
Matchan, Angela
McKean-Cowdin, Roberta
McLeod, Olga
Metcalf, Ginger A.
Mohlke, Karen L.
Muzny, Donna M.
Ntalla, Ioanna
Palmer, Nicholette D.
Pasko, Dorota
Peter, Andreas
Rayner, Nigel W.
Renstroem, Frida
Rice, Ken
Sala, Cinzia F.
Sennblad, Bengt
Serafetinidis, Ioannis
Smith, Jennifer A.
Soranzo, Nicole
Speliotes, Elizabeth K.
Stahl, Eli A.
Stirrups, Kathleen
Tentolouris, Nikos
Thanopoulou, Anastasia
Torres, Mina
Traglia, Michela
Tsafantakis, Emmanouil
Javad, Sundas
Yanek, Lisa R.
Zengini, Eleni
Becker, Diane M.
Bis, Joshua C.
Brown, James B.
Cupples, L. Adrienne
Hansen, Torben
Ingelsson, Erik
Karter, Andrew J.
Lorenzo, Carlos
Mathias, Rasika A.
Norris, Jill M.
Peloso, Gina M.
Sheu, Wayne H. -H.
Toniolo, Daniela
Vaidya, Dhananjay
Varma, Rohit
Wagenknecht, Lynne E.
Boeing, Heiner
Bottinger, Erwin P.
Dedoussis, George
Deloukas, Panos
Ferrannini, Ele
Franco, Oscar H.
Franks, Paul W.
Gibbs, Richard A.
Gudnason, Vilmundur
Hamsten, Anders
Harris, Tamara B.
Hattersley, Andrew T.
Hayward, Caroline
Hofman, Albert
Jansson, Jan-Hakan
Langenberg, Claudia
Launer, Lenore J.
Levy, Daniel
Oostra, Ben A.
O'Donnell, Christopher J.
O'Rahilly, Stephen
Padmanabhan, Sandosh
Pankow, James S.
Polasek, Ozren
Province, Michael A.
Rich, Stephen S.
Ridker, Paul M.
Rudan, Igor
Schulze, Matthias B.
Smith, Blair H.
Uitterlinden, Andre G.
Walker, Mark
Watkins, Hugh
Wong, Tien Y.
Zeggini, Eleftheria
Laakso, Markku
Borecki, Ingrid B.
Chasman, Daniel I.
Pedersen, Oluf
Psaty, Bruce M.
Tai, E. Shyong
van Duijn, Cornelia M.
Wareham, Nicholas J.
Waterworth, Dawn M.
Boerwinkle, Eric
Kao, W. H. Linda
Florez, Jose C.
Loos, Ruth J. F.
Wilson, James G.
Frayling, Timothy M.
Siscovick, David S.
Dupuis, Josee
Rotter, Jerome I.
Meigs, James B.
Scott, Robert A.
Goodarzi, Mark O.
Sharp, Stephen J.
Forouhi, Nita G.
Kerrison, Nicola D.
Lucarelli, Debora M. E.
Sims, Matt
Barroso, Ines
McCarthy, Mark I.
Arriola, Larraitz
Balkau, Beverley
Barricarte, Aurelio
Gonzalez, Carlos
Grioni, Sara
Kaaks, Rudolf
Key, Timothy J.
Navarro, Carmen
Nilsson, Peter M.
Overvad, Kim
Palli, Domenico
Panico, Salvatore
Quiros, J. Ramon
Rolandsson, Olov
Sacerdote, Carlotta
Sanchez, Maria-Jose
Slimani, Nadia
Tjonneland, Anne
Tumino, Rosario
van der A, Daphne L.
van der Schouw, Yvonne T.
Riboli, Elio
CA The EPIC-InterAct Consortium
TI Low-frequency and rare exome chip variants associate with fasting
glucose and type 2 diabetes susceptibility
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GLUCAGON-LIKE PEPTIDE-1; GENOME-WIDE ASSOCIATION; RECEPTOR GENE;
TRIGLYCERIDE LEVELS; GERMLINE MUTATIONS; INSULIN-RESISTANCE; CODING
VARIATION; GLYCEMIC TRAITS; SEQUENCING DATA; PLASMA-GLUCOSE
AB Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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EM robert.scott@mrc-epid.cam.ac.uk; mark.goodarzi@cshs.org
RI Grioni, Sara/K-5320-2016; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Grarup,
Niels/K-2807-2015; Gudnason, Vilmundur/K-6885-2015; Polasek,
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OI Hattersley, Andrew/0000-0001-5620-473X; Dehghan,
Abbas/0000-0001-6403-016X; Linneberg, Allan/0000-0002-0994-0184; Sabater
Lleal, Maria/0000-0002-0128-379X; Schulze, Matthias
B./0000-0002-0830-5277; Sacerdote, Carlotta/0000-0002-8008-5096;
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Torben/0000-0001-9453-2830; Watkins, Hugh/0000-0002-5287-9016; Khor,
Chiea Chuen/0000-0002-1128-4729; Varga, Tibor/0000-0002-2383-699X;
Smith, Blair/0000-0002-5362-9430; Vaidya, Dhananjay/0000-0002-7164-1601;
Smith, Jennifer/0000-0002-3575-5468; Tai, E Shyong/0000-0003-2929-8966;
Pankow, James/0000-0001-7076-483X; Strawbridge,
Rona/0000-0001-8506-3585; Malerba, Giovanni/0000-0001-8705-8560;
THANOPOULOU, ANASTASIA/0000-0002-2902-8053; Peters,
Marjolein/0000-0003-3167-9063; Padmanabhan, Sandosh/0000-0003-3869-5808;
Zeggini, Eleftheria/0000-0003-4238-659X; Wessel,
Jennifer/0000-0002-7031-0085; Grioni, Sara/0000-0002-5891-8426;
SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Grarup,
Niels/0000-0001-5526-1070; Franks, Paul/0000-0002-0520-7604; Soranzo,
Nicole/0000-0003-1095-3852; Gudnason, Vilmundur/0000-0001-5696-0084;
Polasek, Ozren/0000-0002-5765-1862; Smith, Albert/0000-0003-1942-5845;
Schurmann, Claudia/0000-0003-4158-9192; Deloukas,
Panos/0000-0001-9251-070X; Dauriz, Marco/0000-0002-5542-5941; Meidtner,
Karina/0000-0001-5810-4062
FU NIH through the American Recovery and Reinvestment Act [5RC2HL102419];
Eric Boerwinkle on behalf of the Atherosclerosis Risk in Communities
(ARIC) Study; NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086,
HL080295, HL087652, HL103612, HL068986, N02-HL-6-4278]; CHARGE
infrastructure grant [HL105756]; LDRD [14-200, 4R00HG006698-03]; NIA
[N01-AG-12100, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1];
NEI; NIDCD; NIA Intramural Research Program; Hjartavernd (the Icelandic
Heart Association); Althingi (the Icelandic Parliament); National Heart,
Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694, N01-HC-95159, N01-HC-95169, RR-024156];
National Human Genome Research Institute [U01HG004402]; National
Institutes of Health [HHSN268200625226C, U01-HG004729, R01-HL093029,
R01-HL084099]; NIH Roadmap for Medical Research; National Heart, Lung,
and Blood Institute; University of Alabama at Birmingham
[HHSN268201300025C, HHSN268201300026C]; Northwestern University
[HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser
Foundation Research Institute [HHSN268201300029C]; Johns Hopkins
University School of Medicine [HHSN268200900041C]; Intramural Research
Program of the National Institute on Aging; Chinese-American Eye Study
(CHES) [EY017337]; Research to Prevent Blindness; Genetics of Latinos
Diabetic Retinopathy (GOLDR) [EY14684]; National Institute of
Neurological Disorders and Stroke (NINDS); National Institute on Aging
(NIA) [AG023629]; National Center for Advancing Translational Sciences;
CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and
Kidney Disease Diabetes Research Center (DRC) [DK063491];
GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne,
Switzerland; Swiss National Science Foundation [3200B0-105993,
33CSCO-122661]; GlaxoSmithKline (Drug Discovery-Verona, RD); Medical
Research Council UK; Ministry of Science, Education and Sport in the
Republic of Croatia [108-1080315-0302]; South West NHS Research and
Development; Exeter NHS Research and Development; Darlington Trust;
Peninsula NIHR Clinical Research Facility at the University of Exeter;
European Research Council [SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC,
ERC-2011-StG 280559-SEPI]; German Federal Ministry of Education and
Research (BMBF); Federal Ministry of Science, Germany [01 EA 9401];
European Union [SOC 95201408 05 F02]; German Cancer Aid [70-2488-Ha I];
European Community [SOC 98200769 05 F02]; Netherlands Organization for
Scientific Research (NWO); NWO; Russian Foundation for Basic research
[047.016.009, 047.017.043]; Erasmus MC; Centre for Medical Systems
Biology (CMSB; National Genomics Initiative); ZonMw [91111025]; NIH from
NHLBI [R01-HL-087700, R01-HL-088215]; NIH from NIDDK [R01-DK-8925601,
R01-DK-075681]; Medical Research Council [MC_U106179471, G0700931];
Wellcome Trust [098051, WT098051, WT091310, 084723/Z/08/Z]; National
Heart, Lung and Blood Institute Division of Intramural Research;
National Institute for Diabetes and Digestive and Kidney Diseases
(NIDDK) [R01 DK078616, R01DK079888, P30DK063491]; NIDDK [K24 DK080140];
American Diabetes Association Mentor-Based Postdoctoral Fellowship
[7-09-MN-32]; Canadian Diabetes Association Research Fellowship Award;
University of Verona, Italy; NIDDK Research Career Award [K23 DK65978];
Massachusetts General Hospital Physician Scientist Development Award;
Doris Duke Charitable Foundation Clinical Scientist Development Award;
Swedish Heart-Lung Foundation; Umea Medical Research Foundation;
Vasterbotten County Council; NIH grants through the National Heart,
Lung, and Blood Institute [HL58625-01A1, HL59684, HL071025-01A1,
U01HL72518, HL112064, HL087698]; National Institute of Nursing Research
[NR0224103]; U.S. Federal Government from the National Heart, Lung, and
Blood Institute [HHSN268201100037C]; Novo Nordisk; Swedish Research
Council; Pahlssons Foundation; Heart Foundation of Northern Sweden;
Swedish Heart Lung Foundation; Skane Regional Health Authority; Swedish
Diabetes Association; Chief Scientist Office of the Scottish Government
Health Directorates [CZD/16/6]; Scottish Funding Council; Faculty of
Biology and Medicine of Lausanne; Intramural Research Program of the
NIH, National Institute on Aging [Z01 AG000949-02, Z01 AG007390-07];
Timber Merchant Vilhelm Bang's Foundation; Danish Heart Foundation
[07-10-R61-A1754-B838-22392F]; Health Insurance Foundation (Helsefonden)
[2012B233]; EU FP7 [257082, HEALTH-F5-2011-282510]; Danish Research
Council; Danish Centre for Health Technology Assessment; Novo Nordisk
Inc.; Research Foundation of Copenhagen County; Ministry of Internal
Affairs and Health; Danish Heart Foundation; Danish Pharmaceutical
Association; Augustinus Foundation; Ib Henriksen Foundation; Becket
Foundation; Danish Diabetes Association; Lundbeck Foundation; Novo
Nordisk Foundation; EU FP6 programme [LSHM_CT_2006_037197]; Andrea and
Charles Bronfman Philanthropies; Department of Scientific Computing at
the Icahn School of Medicine at Mount Sinai; National Institute of
Diabetes and Digestive and Kidney Diseases [HL060944, HL061019,
HL060919, HL047887, HL047889, HL047890, HL47902]; National Heart, Lung
and Blood Institute [HHSN268201300046C, HHSN268201300047C,
HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National
Institute on Minority Health and Health Disparities; NHLBI of the
National Institutes of Health [R01HL107816]; National Institute for
Health Research Comprehensive Biomedical Research Centre Imperial
College Healthcare NHS Trust; British Heart Foundation [SP/04/002];
National Institute for Health Research [RP-PG-0407-10371]; United States
Environmental Protection Agency (EPA) [RD83169701]; National Center for
Advancing Translational Sciences [UL1-TR000124]; Cedars-Sinai Winnick
Clinical Scholars Award; Academy of Finland [77299, 124243]; NIH
[DK062370, DK093757, DK072193]; Diabetes UK; Magnus Bergvall Foundation;
Foundation for Old Servants; Tore Nilsson foundation; Fredrik and Ingrid
Thuring foundation; Ake-wiberg Foundation; Karolinska Institutet
Foundation; Swedish e-science Research Center (SeRC); EU
[QLG1-CT-2001-01252]; AstraZeneca (Sweden); European Union grant
[QLG1-CT-2001-01252]; AstraZeneca; Boehringer-Ingelheim; LillyCo;
Research Institute for Diseases in the Elderly [014-93-015; RIDE2];
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO) [050-060-810]; CHANCES [242244]; Erasmus
Medical Center; Erasmus University Rotterdam; Netherlands Organization
for the Health Research and Development (ZonMw); Research Institute for
Diseases in the Elderly (RIDE); Ministry of Education, Culture and
Science; Ministry for Health, Welfare and Sports; European Commission
(DG XII); Municipality of Rotterdam; NWO grant veni (veni) [916.12.154];
EUR Fellowship; Foundation for Strategic Research; Swedish Research
Council [8691, 12660, 20653]; European Commission [LSHM-CT-2007-037273];
Knut and Alice Wallenberg Foundation; Torsten and Ragnar Soderberg
Foundation; Strategic Cardiovascular and Diabetes Programmes of
Karolinska Institutet; Stockholm County Council [560183]; National
Medical Research Council (NMRC), Singapore [0796/2003, IRG07nov013,
IRG09nov014, NMRC 1176/2008, STaR/0003/2008, CG/SERI/2010]; Biomedical
Research Council (BMRC), Singapore [08/1/35/19/550, 09/1/35/19/616];
European Union (European Social Fund-ESF); National Strategic Reference
Framework (NSRF); Uppsala University; Knut och Alice Wallenberg
Foundation; European Research Council; Swedish Diabetes Foundation
[2013-024]; Swedish Heart-Lung Foundation [20120197]; Wellcome Trust
Research Career Development Fellowship [086596/Z/08/Z]; Fondazione
Compagnia di San Paolo-Torino; Fondazione Cariplo-Milano; Italian
Ministry of Health Progetto Finalizzato; Italian Ministry of Health
Progetto [CCM 2010, PRIN 2009]; National Heart, Lung, and Blood
Institute [HL043851, HL080467]; National Cancer Institute [CA047988];
Donald W. Reynolds Foundation; Fondation Leducq; [HL120393];
[UL1RR025005]; [M01-RR000052]; [DK081350]; [HG007112];
[R01HL071051]; [R01HL071205]; [R01HL071250]; [R01HL071251];
[R01HL071252]; [R01HL071258]; [R01HL071259]
FX CHARGE: Funding support for 'Building on GWAS for NHLBI-diseases: the
U.S. CHARGE consortium' was provided by the NIH through the American
Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). Sequence
data for 'Building on GWAS for NHLBI-diseases: the U.S. CHARGE
consortium' was provided by Eric Boerwinkle on behalf of the
Atherosclerosis Risk in Communities (ARIC) Study, L. Adrienne Cupples,
principal investigator for the Framingham Heart Study, and Bruce Psaty,
principal investigator for the Cardiovascular Health Study. Sequencing
was carried out at the Baylor Genome Center (U54 HG003273). Further
support came from HL120393, 'Rare variants and NHLBI traits in deeply
phenotyped cohorts' (Bruce Psaty, principal investigator). Supporting
funding was also provided by NHLBI with the CHARGE infrastructure grant
HL105756. In addition, M.J.P. was supported through the 2014 CHARGE
Visiting Fellow grant-HL105756, Dr Bruce Psaty, PI.; ENCODE: ENCODE
collaborators Ben Brown and Marcus Stoiber were supported by the LDRD#
14-200 (B.B. and M.S.) and 4R00HG006698-03 (B.B.) grants.; AGES: This
study has been funded by NIA contract N01-AG-12100 with contributions
from NEI, NIDCD and NHLBI, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association) and the Althingi (the
Icelandic Parliament).; ARIC: The Atherosclerosis Risk in Communities
(ARIC) Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute (NHLBI) contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C and HHSN268201100012C), R01HL087641, R01HL59367 and
R01HL086694; National Human Genome Research Institute contract
U01HG004402; and National Institutes of Health contract
HHSN268200625226C. We thank the staff and participants of the ARIC study
for their important contributions. Infrastructure was partly supported
by Grant Number UL1RR025005, a component of the National Institutes of
Health and NIH Roadmap for Medical Research.; CARDIA: The CARDIA Study
is conducted and supported by the National Heart, Lung, and Blood
Institute in collaboration with the University of Alabama at Birmingham
(HHSN268201300025C & HHSN268201300026C), Northwestern University
(HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser
Foundation Research Institute (HHSN268201300029C), and Johns Hopkins
University School of Medicine (HHSN268200900041C). CARDIA is also
partially supported by the Intramural Research Program of the National
Institute on Aging. Exome chip genotyping and data analyses were funded
in part by grants U01-HG004729, R01-HL093029 and R01-HL084099 from the
National Institutes of Health to Dr Myriam Fornage. This manuscript has
been reviewed by CARDIA for scientific content.; CHES: This work was
supported in part by The Chinese-American Eye Study (CHES) grant
EY017337, an unrestricted departmental grant from Research to Prevent
Blindness, and the Genetics of Latinos Diabetic Retinopathy (GOLDR)
Study grant EY14684.; CHS: This CHS research was supported by NHLBI
contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI
grants HL080295, HL087652, HL103612, HL068986 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. The
provision of genotyping data was supported in part by the National
Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and
the National Institute of Diabetes and Digestive and Kidney Disease
Diabetes Research Center (DRC) grant DK063491 to the Southern California
Diabetes Endocrinology Research Center. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.; The CoLaus Study:
We thank the co-primary investigators of the CoLaus study, Gerard Waeber
and Peter Vollenweider, and the PI of the PsyColaus Study Martin
Preisig. We gratefully acknowledge Yolande Barreau, Anne-Lise Bastian,
Binasa Ramic, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne
Ecoffey and Sylvie Mermoud for their role in the CoLaus data collection.
The CoLaus study was supported by research grants from GlaxoSmithKline
and from the Faculty of Biology and Medicine of Lausanne, Switzerland.
The PsyCoLaus study was supported by grants from the Swiss National
Science Foundation (#3200B0-105993) and from GlaxoSmithKline (Drug
Discovery-Verona, R&D).; CROATIA-Korcula: The CROATIA-Korcula study
would like to acknowledge the invaluable contributions of the
recruitment team in Korcula, the administrative teams in Croatia and
Edinburgh and the people of Korcula. Exome array genotyping was
performed at the Wellcome Trust Clinical Research Facility Genetics Core
at Western General Hospital, Edinburgh, UK. The CROATIA-Korcula study on
the Croatian island of Korucla was supported through grants from the
Medical Research Council UK and the Ministry of Science, Education and
Sport in the Republic of Croatia (number 108-1080315-0302).; EFSOCH: We
are extremely grateful to the EFSOCH study participants and the EFSOCH
study team. The opinions given in this paper do not necessarily
represent those of NIHR, the NHS or the Department of Health. The EFSOCH
study was supported by South West NHS Research and Development, Exeter
NHS Research and Development, the Darlington Trust, and the Peninsula
NIHR Clinical Research Facility at the University of Exeter. Timothy
Frayling, PI, is supported by the European Research Council grant:
SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC.; EPIC-Potsdam: We thank all
EPIC-Potsdam participants for their invaluable contribution to the
study. The study was supported in part by a grant from the German
Federal Ministry of Education and Research (BMBF) to the German Center
for Diabetes Research (DZD e.V.). The recruitment phase of the
EPIC-Potsdam study was supported by the Federal Ministry of Science,
Germany (01 EA 9401) and the European Union (SOC 95201408 05 F02). The
follow-up of the EPIC-Potsdam study was supported by German Cancer Aid
(70-2488-Ha I) and the European Community (SOC 98200769 05 F02).
Furthermore, we thank Ellen Kohlsdorf for data management as well as the
follow-up team headed by Dr Manuala Bergmann for case ascertainment.;
ERF: The ERF study was supported by grants from the Netherlands
Organization for Scientific Research (NWO) and a joint grant from NWO
and the Russian Foundation for Basic research (Pionier, 047.016.009,
047.017.043), Erasmus MC, and the Centre for Medical Systems Biology
(CMSB; National Genomics Initiative). Exome sequencing analysis in ERF
was supported by the ZonMw grant (91111025).; For the ERF Study, we are
grateful to all participants and their relatives, to general
practitioners and neurologists for their contributions, to P. Veraart
for her help in genealogy and to P. Snijders for his help in data
collection.; FamHS: The Family Heart Study (FamHS) was supported by NIH
grants R01-HL-087700 and R01-HL-088215 (Michael A. Province, PI) from
NHLBI; and R01-DK-8925601 and R01-DK-075681 (Ingrid B. Borecki, PI) from
NIDDK.; FENLAND: The Fenland Study is funded by the Medical Research
Council (MC_U106179471) and Wellcome Trust. We are grateful to all the
volunteers for their time and help, and to the General Practitioners and
practice staff for assistance with recruitment. We thank the Fenland
Study Investigators, Fenland Study Co-ordination team and the
Epidemiology Field, Data and Laboratory teams. The Fenland Study is
funded by the Medical Research Council (MC_U106179471) and Wellcome
Trust.; FHS: Genotyping, quality control and calling of the Illumina
HumanExome BeadChip in the Framingham Heart Study was supported by
funding from the National Heart, Lung and Blood Institute Division of
Intramural Research (Daniel Levy and Christopher J. O'Donnell, Principle
Investigators). A portion of this research was conducted using the Linux
Clusters for Genetic Analysis (LinGA) computing resources at Boston
University Medical Campus. Also supported by National Institute for
Diabetes and Digestive and Kidney Diseases (NIDDK) R01 DK078616, NIDDK
K24 DK080140 and American Diabetes Association Mentor-Based Postdoctoral
Fellowship Award #7-09-MN-32, all to Dr Meigs, a Canadian Diabetes
Association Research Fellowship Award to Dr Leong, a research grant from
the University of Verona, Italy to Dr Dauriz, and NIDDK Research Career
Award K23 DK65978, a Massachusetts General Hospital Physician Scientist
Development Award and a Doris Duke Charitable Foundation Clinical
Scientist Development Award to Dr Florez.; FIA3: We are indebted to the
study participants who dedicated their time and samples to these
studies. We thank Asa Agren (Umea Medical Biobank) for data organization
and Kerstin Enquist and Thore Johansson (Vasterbottens County Council)
for technical assistance with DNA extraction. This particular project
was supported by project grants from the Swedish Heart-Lung Foundation,
Umea Medical Research Foundation and Vasterbotten County Council.; The
Genetics Epidemiology of Metabolic Syndrome (GEMS) Study: We thank
Metabolic Syndrome GEMs investigators: Scott Grundy, Jonathan Cohen,
Ruth McPherson, Antero Kesaniemi, Robert Mahley, Tom Bersot, Philip
Barter and Gerard Waeber. We gratefully acknowledge the contributions of
the study personnel at each of the collaborating sites: John Farrell,
Nicholas Nikolopoulos and Maureen Sutton (Boston); Judy Walshe, Monica
Prentice, Anne Whitehouse, Julie Butters and Tori Nicholls (Australia);
Heather Doelle, Lynn Lewis and Anna Toma (Canada); Kari Kervinen, Seppo
Poykko, Liisa Mannermaa and Sari Paavola (Finland); Claire Hurrel, Diane
Morin, Alice Mermod, Myriam Genoud and Roger Darioli (Switzerland); Guy
Pepin, Sibel Tanir, Erhan Palaoglu, Kerem Ozer, Linda Mahley and Aysen
Agacdiken (Turkey); and Deborah A. Widmer, Rhonda Harris and Selena
Dixon (United States). Funding for the GEMS study was provided by
GlaxoSmithKline.; GeneSTAR: The Johns Hopkins Genetic Study of
Atherosclerosis Risk (GeneSTAR) Study was supported by NIH grants
through the National Heart, Lung, and Blood Institute (HL58625-01A1,
HL59684, HL071025-01A1, U01HL72518, HL112064, and HL087698) and the
National Institute of Nursing Research (NR0224103) and by M01-RR000052
to the Johns Hopkins General Clinical Research Center. Genotyping
services were provided through the RS&G Service by the Northwest
Genomics Center at the University of Washington, Department of Genome
Sciences, under U.S. Federal Government contract number
HHSN268201100037C from the National Heart, Lung, and Blood Institute.;
GLACIER: We are indebted to the study participants who dedicated their
time, data and samples to the GLACIER Study as part of the Vasterbottens
halsoundersokningar (Vasterbottens Health Survey). We thank John
Hutiainen and Asa Agren (Northern Sweden Biobank) for data organization
and Kerstin Enquist and Thore Johansson (Vasterbottens County Council)
for extracting DNA. We also thank M. Sterner, M. Juhas and P. Storm
(Lund University Diabetes Center) for their expert technical assistance
with genotyping and genotype data preparation. The GLACIER Study was
supported by grants from Novo Nordisk, the Swedish Research Council,
Pahlssons Foundation, The Heart Foundation of Northern Sweden, the
Swedish Heart Lung Foundation, the Skane Regional Health Authority, Umea
Medical Research Foundation and the Wellcome Trust. This particular
project was supported by project grants from the Swedish Heart-Lung
Foundation, the Swedish Research Council, the Swedish Diabetes
Association, Pahlssons Foundation and Novo nordisk (all grants to P. W.
Franks).; GOMAP (Genetic Overlap between Metabolic and Psychiatric
Disease): This work was funded by the Wellcome Trust (098051). We thank
all participants for their important contribution. We are grateful to
Georgia Markou, Laiko General Hospital Diabetes Centre, Maria Emetsidou
and Panagiota Fotinopoulou, Hippokratio General Hospital Diabetes
Centre, Athina Karabela, Dafni Psychiatric Hospital, Eirini Glezou and
Marios Matzioros, Dromokaiteio Psychiatric Hospital, Angela Rentari,
Harokopio University of Athens, and Danielle Walker, Wellcome Trust
Sanger Institute.; Generation Scotland: Scottish Family Health Study
(GS:SFHS): GS:SFHS is funded by the Chief Scientist Office of the
Scottish Government Health Directorates, grant number CZD/16/6 and the
Scottish Funding Council. Exome array genotyping for GS:SFHS was funded
by the Medical Research Council UK and performed at the Wellcome Trust
Clinical Research Facility Genetics Core at Western General Hospital,
Edinburgh, UK. We also acknowledge the invaluable contributions of the
families who took part in the Generation Scotland: Scottish Family
Health Study, the general practitioners and Scottish School of Primary
Care for their help in recruiting them, and the whole Generation
Scotland team, which includes academic researchers, IT staff, laboratory
technicians, statisticians and research managers. The chief
investigators of Generation Scotland are David J. Porteous (University
of Edinburgh), Lynne Hocking (University of Aberdeen), Blair Smith
(University of Dundee), and Sandosh Padmanabhan (University of
Glasgow).; GSK (CoLaus, GEMS, Lolipop): We thank the GEMS Study
Investigators: Philip Barter, PhD; Y. Antero Kesaniemi, PhD; Robert W.
Mahley, PhD; Ruth McPherson, FRCP; and Scott M. Grundy, PhD. Dr Waeber
MD, the CoLaus PI's Peter Vollenweider MD and Gerard Waeber MD, the
LOLIPOP PI's, Jaspal Kooner MD and John Chambers MD, as well as the
participants in all the studies. The GEMS study was sponsored in part by
GlaxoSmithKline. The CoLaus study was supported by grants from
GlaxoSmithKline, the Swiss National Science Foundation (Grant
33CSCO-122661) and the Faculty of Biology and Medicine of Lausanne.;
Health ABC: The Health, Aging and Body Composition (HABC) Study is
supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The
exome-wide association study was funded by NIA grant 1R01AG032098-01A1
to Wake Forest University Health Sciences and was supported in part by
the Intramural Research Program of the NIH, National Institute on Aging
(Z01 AG000949-02 and Z01 AG007390-07, Human subjects protocol UCSF IRB
is H5254-12688-11). Portions of this study utilized the high-performance
computational capabilities of the Biowulf Linux cluster at the National
Institutes of Health, Bethesda, MD. (http:/biowulf.nih.gov).;
Health2008: The Health2008 cohort was supported by the Timber Merchant
Vilhelm Bang's Foundation, the Danish Heart Foundation (Grant number
07-10-R61-A1754-B838-22392F), and the Health Insurance Foundation
(Helsefonden) (Grant number 2012B233).; HELIC: This work was funded by
the Wellcome Trust (098051) and the European Research Council
(ERC-2011-StG 280559-SEPI). The MANOLIS cohort is named in honour of
Manolis Giannakakis, 1978-2010. We thank the residents of Anogia and
surrounding Mylopotamos villages, and of the Pomak villages, for taking
part. The HELIC study has been supported by many individuals who have
contributed to sample collection (including Antonis Athanasiadis, Olina
Balafouti, Christina Batzaki, Georgios Daskalakis, Eleni Emmanouil,
Chrisoula Giannakaki, Margarita Giannakopoulou,; Anastasia Kaparou,
Vasiliki Kariakli, Stella Koinaki, Dimitra Kokori, Maria Konidari, Hara
Koundouraki, Dimitris Koutoukidis, Vasiliki Mamakou, Eirini Mamalaki,
Eirini Mpamiaki, Maria Tsoukana, Dimitra Tzakou, Katerina Vosdogianni,
Niovi Xenaki, Eleni Zengini), data entry (Thanos Antonos, Dimitra
Papagrigoriou, Betty Spiliopoulou), sample logistics (Sarah Edkins, Emma
Gray), genotyping (Robert Andrews, Hannah Blackburn, Doug Simpkin,
Siobhan Whitehead), research administration (Anja Kolb-Kokocinski, Carol
Smee, Danielle Walker) and informatics (Martin Pollard, Josh Randall).;
INCIPE: NIcole Soranzo's research is supported by the Wellcome Trust
(Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code
257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510).; Inter99: The
Inter99 was initiated by Torben Jorgensen (PI), Knut Borch-Johnsen
(co-PI), Hans Ibsen and Troels F. Thomsen. The steering committee
comprises the former two and Charlotta Pisinger. The study was
financially supported by research grants from the Danish Research
Council, the Danish Centre for Health Technology Assessment, Novo
Nordisk Inc., Research Foundation of Copenhagen County, Ministry of
Internal Affairs and Health, the Danish Heart Foundation, the Danish
Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen
Foundation, the Becket Foundation and the Danish Diabetes Association.
Genetic studies of both Inter99 and Health 2008 cohorts were funded by
the Lundbeck Foundation and produced by The Lundbeck Foundation Centre
for Applied Medical Genomics in Personalised Disease Prediction,
Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk
Foundation Center for Basic Metabolic Research is an independent
Research Center at the University of Copenhagen partially funded by an
unrestricted donation from the Novo Nordisk Foundation
(www.metabol.ku.dk).; InterAct Consortium: Funding for the InterAct
project was provided by the EU FP6 programme (grant number
LSHM_CT_2006_037197). We thank all EPIC participants and staff for their
contribution to the study. We thank the lab team at the MRC Epidemiology
Unit for sample management and Nicola Kerrison for data management.; IPM
BioMe Biobank: The Mount Sinai IPM BioMe Program is supported by The
Andrea and Charles Bronfman Philanthropies. Analyses of BioMe data was
supported in part through the computational resources and staff
expertise provided by the Department of Scientific Computing at the
Icahn School of Medicine at Mount Sinai.; The Insulin Resistance
Atherosclerosis Family Study (IRASFS): The IRASFS was conducted and
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases (HL060944, HL061019, and HL060919). Exome chip genotyping and
data analyses were funded in part by grants DK081350 and HG007112. A
subset of the IRASFS exome chips were contributed with funds from the
Department of Internal Medicine at the University of Michigan. Computing
resources were provided, in part, by the Wake Forest School of Medicine
Center for Public Health Genomics.; The Insulin Resistance
Atherosclerosis Study (IRAS): The IRAS was conducted and supported by
the National Institute of Diabetes and Digestive and Kidney Diseases
(HL047887, HL047889, HL047890 and HL47902). Exome chip genotyping and
data analyses were funded in part by grants DK081350 and HG007112).
Computing resources were provided, in part, by the Wake Forest School of
Medicine Center for Public Health Genomics.; JHS: The JHS is supported
by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C from the National Heart, Lung and
Blood Institute and the National Institute on Minority Health and Health
Disparities. ExomeChip genotyping was supported by the NHLBI of the
National Institutes of Health under award number R01HL107816 to S.
Kathiresan. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.; The London Life Sciences Prospective Population
(LOLIPOP) Study: We thank the co-primary investigators of the LOLIPOP
study: Jaspal Kooner, John Chambers and Paul Elliott. The LOLIPOP study
is supported by the National Institute for Health Research Comprehensive
Biomedical Research Centre Imperial College Healthcare NHS Trust, the
British Heart Foundation (SP/04/002), the Medical Research Council
(G0700931), the Wellcome Trust (084723/Z/08/Z) and the National
Institute for Health Research (RP-PG-0407-10371).; MESA: The
Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SHARe project are
conducted and supported by contracts N01-HC-95159 through N01-HC-95169
and RR-024156 from the National Heart, Lung, and Blood Institute
(NHLBI). Funding for MESA SHARe genotyping was provided by NHLBI
Contract N02-HL-6-4278. MESA Family is conducted and supported in
collaboration with MESA investigators; support is provided by grants and
contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251,
R01HL071252, R01HL071258, R01HL071259. MESA Air is conducted and
supported by the United States Environmental Protection Agency (EPA) in
collaboration with MESA Air investigators; support is provided by grant
RD83169701. We thank the participants of the MESA study, the
Coordinating Center, MESA investigators, and study staff for their
valuable contributions. A full list of participating MESA investigators
and institutions can be found at http://www.mesa-nhlbi.org. Additional
support was provided by the National Institute for Diabetes and
Digestive and Kidney Diseases (NIDDK) grants R01DK079888 and P30DK063491
and the National Center for Advancing Translational Sciences grant
UL1-TR000124. Further support came from the Cedars-Sinai Winnick
Clinical Scholars Award (to M.O. Goodarzi).; METSIM: The METSIM study
was funded by the Academy of Finland (grants no. 77299 and 124243). M.L.
acknowledges funding from the Academy of Finland. M.B. and K.M.
acknowledge grant funding from NIH grants DK062370, DK093757, DK072193.;
MRC Ely: The Ely Study was funded by the Medical Research Council
(MC_U106179471) and Diabetes UK. We are grateful to all the volunteers,
and to the staff of St Mary's Street Surgery, Ely and the study team.;
PROCARDIS: We thank all participants in this study. The European
Community Sixth Framework Program (LSHM-CT-2007-037273), AstraZeneca,
the British Heart Foundation, the Oxford British Heart Foundation Centre
of Research Excellence, the Wellcome Trust (075491/Z/04), the Swedish
Research Council, the Knut and Alice Wallenberg Foundation, the Swedish
Heart-Lung Foundation, the Torsten and Ragnar Soderberg Foundation, the
Strategic Cardiovascular and Diabetes Programs of Karolinska Institutet
and Stockholm County Council, the Foundation for Strategic Research and
the Stockholm County Council (560283). Bengt Sennblad acknowledges
funding from the Magnus Bergvall Foundation and the Foundation for Old
Servants. Rona J. Strawbridge is supported by the Swedish Heart-Lung
Foundation, the Tore Nilsson foundation, the Fredrik and Ingrid Thuring
foundation and the Foundation for Old Servants. Maria Sabater-Lleal
acknowledges funding from Ake-wiberg, Tore Nilsson and Karolinska
Institutet Foundations. Mattias Frnberg acknowledges funding from the
Swedish e-science Research Center (SeRC).; RISC: We are extremely
grateful to the RISC study participants and the RISC study team. The
RISC Study is partly supported by EU grant QLG1-CT-2001-01252.
Additional support for the RISC Study has been provided by AstraZeneca
(Sweden). The RISC Study was supported by European Union grant
QLG1-CT-2001-01252 and AstraZeneca. Ele Ferrannini acknowledges grant
funding from Boehringer-Ingelheim and Lilly&Co and works as a consultant
for Boehringer-Ingelheim, Lilly&Co., MSD, Sanofi, GSK, Janssen,
Menarini, Novo Nordisk, AstraZeneca.; Rotterdam Study: The Rotterdam
Study is funded by the Research Institute for Diseases in the Elderly
(014-93-015; RIDE2), the Netherlands Genomics Initiative
(NGI)/Netherlands Organization for Scientific Research (NWO) project nr.
050-060-810, CHANCES (nr 242244), Erasmus Medical Center and Erasmus
University Rotterdam, Netherlands Organization for the Health Research
and Development (ZonMw), the Research Institute for Diseases in the
Elderly (RIDE), the Ministry of Education, Culture and Science, the
Ministry for Health, Welfare and Sports, the European Commission (DG
XII) and the Municipality of Rotterdam. Abbas Dehghan is supported by
NWO grant veni (veni, 916.12.154) and the EUR Fellowship. We are
grateful to the study participants, the staff from the Rotterdam Study
and the participating general practitioners and pharmacists.; SCARF: We
thank all participants in this study. The study was funded by the
Foundation for Strategic Research, the Swedish Heart-Lung Foundation,
the Swedish Research Council (8691, 12660, 20653), the European
Commission (LSHM-CT-2007-037273), the Knut and Alice Wallenberg
Foundation, the Torsten and Ragnar Soderberg Foundation, the Strategic
Cardiovascular and Diabetes Programmes of Karolinska Institutet and the
Stockholm County Council, and the Stockholm County Council (560183).
Bengt Sennblad acknowledges funding from the Magnus Bergvall Foundation
and the Foundation for Old Servants. Mattias Franberg acknowledges
funding from the Swedish e-Science Research Center (SeRC).; SCES: The
Singapore Chinese Eye Study (SCES) was supported by the National Medical
Research Council (NMRC), Singapore (grants 0796/2003, IRG07nov013,
IRG09nov014, NMRC 1176/2008, STaR/0003/2008, CG/SERI/2010) and
Biomedical Research Council (BMRC), Singapore (08/1/35/19/550 and
09/1/35/19/616).; TEENAGE (TEENs of Attica: Genes and Environment): This
research has been co-financed by the European Union (European Social
Fund-ESF) and Greek national funds through the Operational Program
'Education and Lifelong Learning' of the National Strategic Reference
Framework (NSRF)-Research Funding Program: Heracleitus II. Investing in
knowledge society through the European Social Fund. This work was funded
by the Wellcome Trust (098051).; Uppsala Longitudinal Study of Adult Men
(ULSAM): The exome chip genotyping and data analyses were supported by
Uppsala University, Knut och Alice Wallenberg Foundation, European
Research Council, Swedish Diabetes Foundation (grant no. 2013-024),
Swedish Research Council (grant no. 2012-1397), and Swedish Heart-Lung
Foundation (20120197). C.M.L. is supported by a Wellcome Trust Research
Career Development Fellowship (086596/Z/08/Z).; INGI-VB: The Val Borbera
study (INGI-VB) thanks the inhabitants of the Val Borbera for
participating in the study, the local administrations and the ASL-Novi
Ligure for support and Fiammetta Vigano for technical help. We also
thank Professor Clara Camaschella, Professor Federico Caligaris-Cappio
and the MDs of the Medicine Dept. of the San Raffaele Hospital for help
with clinical data collection. The study was supported by funds from
Fondazione Compagnia di San Paolo-Torino, Fondazione Cariplo-Milano,
Italian Ministry of Health Progetto Finalizzato 2007 and 2012, Italian
Ministry of Health Progetto CCM 2010, and PRIN 2009.; WGHS: The WGHS is
supported by HL043851 and HL080467 from the National Heart, Lung, and
Blood Institute and CA047988 from the National Cancer Institute, the
Donald W. Reynolds Foundation and the Fondation Leducq, with
collaborative scientific support and funding for genotyping provided by
Amgen.
NR 70
TC 43
Z9 43
U1 5
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 5897
DI 10.1038/ncomms6897
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA2ME
UT WOS:000348741700001
PM 25631608
ER
PT J
AU Ulrich, CM
Grady, C
AF Ulrich, Connie M.
Grady, Christine
TI Cardiopulmonary Resuscitation for Ebola patients: Ethical considerations
SO NURSING OUTLOOK
LA English
DT Article
ID VIRUS DISEASE; WEST-AFRICA
C1 [Ulrich, Connie M.] Univ Penn, Philadelphia, PA 19104 USA.
[Grady, Christine] NIH, Bethastha, MD USA.
RP Ulrich, CM (reprint author), Univ Penn, 420 Curie Blvd, Philadelphia, PA 19104 USA.
EM culrich@nursing.upenn.edu
NR 11
TC 4
Z9 5
U1 0
U2 2
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 JAN-FEB
PY 2015
VL 63
IS 1
BP 16
EP 18
DI 10.1016/j.outlook.2014.11.011
PG 3
WC Nursing
SC Nursing
GA CA9UF
UT WOS:000349269600006
PM 25645475
ER
PT J
AU Matlock, AM
Gutierrez, D
Wallen, G
Hastings, C
AF Matlock, Ann Marie
Gutierrez, Debbie
Wallen, Gwenyth
Hastings, Clare
TI Providing nursing care to Ebola patients on the national stage: The
National Institutes of Health experience
SO NURSING OUTLOOK
LA English
DT Article
C1 [Matlock, Ann Marie; Gutierrez, Debbie; Wallen, Gwenyth; Hastings, Clare] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Hastings, C (reprint author), NIH, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM chastings@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 3
TC 1
Z9 1
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 JAN-FEB
PY 2015
VL 63
IS 1
BP 21
EP 24
DI 10.1016/j.outlook.2014.11.015
PG 4
WC Nursing
SC Nursing
GA CA9UF
UT WOS:000349269600008
PM 25645477
ER
PT J
AU Williams, JK
Cashion, AK
Veenstra, DL
AF Williams, Janet K.
Cashion, Ann K.
Veenstra, David L.
TI Challenges in evaluating next-generation sequence data for clinical
decisions
SO NURSING OUTLOOK
LA English
DT Article
DE Genetics; Genome sequencing; Clinical decisions; Nursing; Clinical
genomics; Genomic medicine; Evidence
ID CARE
C1 [Williams, Janet K.] Univ Iowa, Iowa City, IA 52242 USA.
[Cashion, Ann K.] NINR, NIH, Bethesda, MD 20892 USA.
[Veenstra, David L.] Univ Washington, Seattle, WA 98195 USA.
RP Williams, JK (reprint author), Univ Iowa, 50 Newton Rd, Iowa City, IA 52242 USA.
EM janet-williams@uiowa.edu
NR 12
TC 6
Z9 6
U1 1
U2 2
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 JAN-FEB
PY 2015
VL 63
IS 1
BP 48
EP 50
DI 10.1016/j.outlook.2014.08.007
PG 3
WC Nursing
SC Nursing
GA CA9UF
UT WOS:000349269600013
PM 25261386
ER
PT J
AU Nussinov, R
AF Nussinov, Ruth
TI Advancements and Challenges in Computational Biology
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
ID ENERGY LANDSCAPES
C1 [Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 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), NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM nussinor@helix.nih.gov
NR 5
TC 2
Z9 2
U1 1
U2 5
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 JAN
PY 2015
VL 11
IS 1
AR e1004053
DI 10.1371/journal.pcbi.1004053
PG 2
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CB0IO
UT WOS:000349309400028
PM 25569585
ER
PT J
AU Stepp, N
Plenz, D
Srinivasa, N
AF Stepp, Nigel
Plenz, Dietmar
Srinivasa, Narayan
TI Synaptic Plasticity Enables Adaptive Self-Tuning Critical Networks
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID NEURONAL AVALANCHES; NEURAL-NETWORKS; ORGANIZED CRITICALITY; CORTICAL
NETWORKS; DEPENDENT PLASTICITY; IN-VIVO; RANGE; CIRCUITS; NOISE;
FLUCTUATION
AB During rest, the mammalian cortex displays spontaneous neural activity. Spiking of single neurons during rest has been described as irregular and asynchronous. In contrast, recent in vivo and in vitro population measures of spontaneous activity, using the LFP, EEG, MEG or fMRI suggest that the default state of the cortex is critical, manifested by spontaneous, scale-invariant, cascades of activity known as neuronal avalanches. Criticality keeps a network poised for optimal information processing, but this view seems to be difficult to reconcile with apparently irregular single neuron spiking. Here, we simulate a 10,000 neuron, deterministic, plastic network of spiking neurons. We show that a combination of short-and long-term synaptic plasticity enables these networks to exhibit criticality in the face of intrinsic, i.e. self-sustained, asynchronous spiking. Brief external perturbations lead to adaptive, long-term modification of intrinsic network connectivity through long-term excitatory plasticity, whereas long-term inhibitory plasticity enables rapid self-tuning of the network back to a critical state. The critical state is characterized by a branching parameter oscillating around unity, a critical exponent close to -3/2 and a long tail distribution of a self-similarity parameter between 0.5 and 1.
C1 [Stepp, Nigel; Srinivasa, Narayan] HRL Labs LLC, Informat & Syst Sci Lab, Ctr Neural & Emergent Syst, Malibu, CA 90265 USA.
[Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Lab Syst Neurosci, Bethesda, MD 20892 USA.
RP Stepp, N (reprint author), HRL Labs LLC, Informat & Syst Sci Lab, Ctr Neural & Emergent Syst, Malibu, CA 90265 USA.
EM nsrinivasa@hrl.com
FU Defense Advanced Research Projects Agency (DARPA) [HR0011-10-C-0052];
Division of Intramural Research Program of the National Institute of
Mental Health, NIH, USA
FX This material is based upon work supported by the Defense Advanced
Research Projects Agency (DARPA) under contract HR0011-10-C-0052. Any
opinions, findings and conclusions or recommendations expressed in this
material are those of author(s) and do not necessarily reflect the views
of the Defense Advanced Research Projects Agency. This research was
supported by the Division of Intramural Research Program of the National
Institute of Mental Health, NIH, USA. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 61
TC 5
Z9 5
U1 1
U2 25
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 JAN
PY 2015
VL 11
IS 1
AR e1004043
DI 10.1371/journal.pcbi.1004043
PG 28
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CB0IO
UT WOS:000349309400025
PM 25590427
ER
PT J
AU Mahajan, A
Sim, X
Ng, HJ
Manning, A
Rivas, MA
Highland, HM
Locke, AE
Grarup, N
Im, HK
Cingolani, P
Flannick, J
Fontanillas, P
Fuchsberger, C
Gaulton, KJ
Teslovich, TM
Rayner, NW
Robertson, NR
Beer, NL
Rundle, JK
Bork-Jensen, J
Ladenvall, C
Blancher, C
Buck, D
Buck, G
Burtt, NP
Gabriel, S
Gjesing, AP
Groves, CJ
Hollensted, M
Huyghe, JR
Jackson, AU
Jun, G
Justesen, JM
Mangino, M
Murphy, J
Neville, M
Onofrio, R
Small, KS
Stringham, HM
Syvanen, AC
Trakalo, J
Abecasis, G
Bell, GI
Blangero, J
Cox, NJ
Duggirala, R
Hanis, CL
Seielstad, M
Wilson, JG
Christensen, C
Brandslund, I
Rauramaa, R
Surdulescu, GL
Doney, ASF
Lannfelt, L
Linneberg, A
Isomaa, B
Tuomi, T
Jorgensen, ME
Jorgensen, T
Kuusisto, J
Uusitupa, M
Salomaa, V
Spector, TD
Morris, AD
Palmer, CNA
Collins, FS
Mohlke, KL
Bergman, RN
Ingelsson, E
Lind, L
Tuomilehto, J
Hansen, T
Watanabe, RM
Prokopenko, I
Dupuis, J
Karpe, F
Groop, L
Laakso, M
Pedersen, O
Florez, JC
Morris, AP
Altshuler, D
Meigs, JB
Boehnke, M
McCarthy, MI
Lindgren, CM
Gloyn, AL
AF Mahajan, Anubha
Sim, Xueling
Ng, Hui Jin
Manning, Alisa
Rivas, Manuel A.
Highland, Heather M.
Locke, Adam E.
Grarup, Niels
Im, Hae Kyung
Cingolani, Pablo
Flannick, Jason
Fontanillas, Pierre
Fuchsberger, Christian
Gaulton, Kyle J.
Teslovich, Tanya M.
Rayner, N. William
Robertson, Neil R.
Beer, Nicola L.
Rundle, Jana K.
Bork-Jensen, Jette
Ladenvall, Claes
Blancher, Christine
Buck, David
Buck, Gemma
Burtt, Noel P.
Gabriel, Stacey
Gjesing, Anette P.
Groves, Christopher J.
Hollensted, Mette
Huyghe, Jeroen R.
Jackson, Anne U.
Jun, Goo
Justesen, Johanne Marie
Mangino, Massimo
Murphy, Jacquelyn
Neville, Matt
Onofrio, Robert
Small, Kerrin S.
Stringham, Heather M.
Syvanen, Ann-Christine
Trakalo, Joseph
Abecasis, Goncalo
Bell, Graeme I.
Blangero, John
Cox, Nancy J.
Duggirala, Ravindranath
Hanis, Craig L.
Seielstad, Mark
Wilson, James G.
Christensen, Cramer
Brandslund, Ivan
Rauramaa, Rainer
Surdulescu, Gabriela L.
Doney, Alex S. F.
Lannfelt, Lars
Linneberg, Allan
Isomaa, Bo
Tuomi, Tiinamaija
Jorgensen, Marit E.
Jorgensen, Torben
Kuusisto, Johanna
Uusitupa, Matti
Salomaa, Veikko
Spector, Timothy D.
Morris, Andrew D.
Palmer, Colin N. A.
Collins, Francis S.
Mohlke, Karen L.
Bergman, Richard N.
Ingelsson, Erik
Lind, Lars
Tuomilehto, Jaakko
Hansen, Torben
Watanabe, Richard M.
Prokopenko, Inga
Dupuis, Josee
Karpe, Fredrik
Groop, Leif
Laakso, Markku
Pedersen, Oluf
Florez, Jose C.
Morris, Andrew P.
Altshuler, David
Meigs, James B.
Boehnke, Michael
McCarthy, Mark I.
Lindgren, Cecilia M.
Gloyn, Anna L.
CA T2D-GENES Consortium
Go T2D Consortium
TI Identification and Functional Characterization of G6PC2 Coding Variants
Influencing Glycemic Traits Define an Effector Transcript at the
G6PC2-ABCB11 Locus
SO PLOS GENETICS
LA English
DT Article
ID TYPE-2 DIABETES RISK; FASTING PLASMA-GLUCOSE; GENETIC ARCHITECTURE;
TRIGLYCERIDE LEVELS; QUANTITATIVE TRAIT; P446L VARIANT; ASSOCIATION;
GENOME; PROTEIN; POLYMORPHISMS
AB Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5x10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.
C1 [Mahajan, Anubha; Rivas, Manuel A.; Gaulton, Kyle J.; Rayner, N. William; Robertson, Neil R.; Morris, Andrew D.; Ingelsson, Erik; Prokopenko, Inga; Morris, Andrew P.; McCarthy, Mark I.; Lindgren, Cecilia M.] Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.
[Sim, Xueling; Locke, Adam E.; Fuchsberger, Christian; Teslovich, Tanya M.; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Stringham, Heather M.; Abecasis, Goncalo; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Sim, Xueling; Locke, Adam E.; Fuchsberger, Christian; Teslovich, Tanya M.; Huyghe, Jeroen R.; Jackson, Anne U.; Jun, Goo; Stringham, Heather M.; Abecasis, Goncalo; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Ng, Hui Jin; Rayner, N. William; Robertson, Neil R.; Beer, Nicola L.; Rundle, Jana K.; Groves, Christopher J.; Neville, Matt; Prokopenko, Inga; Karpe, Fredrik; McCarthy, Mark I.; Gloyn, Anna L.] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Manning, Alisa; Flannick, Jason; Fontanillas, Pierre; Burtt, Noel P.; Gabriel, Stacey; Murphy, Jacquelyn; Onofrio, Robert; Florez, Jose C.; Altshuler, David; Lindgren, Cecilia M.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Highland, Heather M.] Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Grarup, Niels; Bork-Jensen, Jette; Gjesing, Anette P.; Hollensted, Mette; Justesen, Johanne Marie; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
[Im, Hae Kyung] Univ Chicago, Dept Hlth Studies, Biostat Lab, Chicago, IL 60637 USA.
[Cingolani, Pablo] McGill Univ, Sch Comp Sci, Montreal, PQ, Canada.
[Cingolani, Pablo] McGill Univ, Montreal, PQ, Canada.
[Cingolani, Pablo] Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
[Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Rayner, N. William] Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, Cambs, England.
[Ladenvall, Claes; Groop, Leif] Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
[Blancher, Christine; Buck, David; Buck, Gemma; Trakalo, Joseph] Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom Oxford Genom Ctr, Oxford, England.
[Mangino, Massimo; Small, Kerrin S.; Surdulescu, Gabriela L.; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Mol Med & Sci Life Lab, Uppsala, Sweden.
[Bell, Graeme I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Bell, Graeme I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Blangero, John; Duggirala, Ravindranath] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
[Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA.
[Hanis, Craig L.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Seielstad, Mark] Blood Syst Res Inst, San Francisco, CA USA.
[Seielstad, Mark] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Christensen, Cramer] Vejle Hosp, Dept Internal Med & Endocrinol, Vejle, Denmark.
[Brandslund, Ivan] Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
[Brandslund, Ivan] Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.
[Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.
[Doney, Alex S. F.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee DD1 9SY, Scotland.
[Lannfelt, Lars] Uppsala Univ, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Linneberg, Allan] Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark.
[Linneberg, Allan] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Linneberg, Allan; Jorgensen, Torben] Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari, Finland.
[Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland.
[Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Endocrinol, Helsinki, Finland.
[Jorgensen, Marit E.] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Jorgensen, Torben] Aalborg Univ, Fac Med, Aalborg, Denmark.
[Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Inst Clin Med Internal Med, Fac Hlth Sci, Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki, Finland.
[Morris, Andrew D.] Univ Dundee, Ninewells Hosp & Med Sch, Clin Res Ctr, Ctr Mol Med, Dundee DD1 9SY, Scotland.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee DD1 9SY, Scotland.
[Collins, Francis S.] NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Bergman, Richard N.] Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA USA.
[Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden.
[Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia.
[Tuomilehto, Jaakko] Autonomous Univ Madrid, Univ Hosp LaPaz, Inst Invest Sanitaria Hosp Univ LaPaz IdiPAZ, E-28049 Madrid, Spain.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Diabet & Obes Res Inst, Los Angeles, CA 90033 USA.
[Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Dupuis, Josee] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Karpe, Fredrik; McCarthy, Mark I.; Gloyn, Anna L.] Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
[Florez, Jose C.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England.
[Morris, Andrew P.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Altshuler, David] MIT, Dept Biol, Cambridge, MA USA.
[Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Meigs, James B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Mahajan, A (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.
EM celi@well.ox.ac.uk; anna.gloyn@drl.ox.ac.uk
RI Palmer, Colin/C-7053-2008; Grarup, Niels/K-2807-2015; Prokopenko,
Inga/H-3241-2014; Justesen, Johanne Marie/L-6023-2015; kinnunen,
leena/B-7059-2012; Study, GoDARTS/K-9448-2016; mangino,
massimo/F-5134-2011; Hrabe de Angelis, Martin/F-5531-2012; Jun,
Goo/F-1941-2017;
OI Gieger, Christian/0000-0001-6986-9554; Meisinger,
Christa/0000-0002-9026-6544; Tuomi, Tiinamaija/0000-0002-8306-6202;
Jorgensen, Torben/0000-0001-9453-2830; Small,
Kerrin/0000-0003-4566-0005; Khor, Chiea Chuen/0000-0002-1128-4729; Tai,
E Shyong/0000-0003-2929-8966; Linneberg, Allan/0000-0002-0994-0184;
Palmer, Colin/0000-0002-6415-6560; Grarup, Niels/0000-0001-5526-1070;
Prokopenko, Inga/0000-0003-1624-7457; Justesen, Johanne
Marie/0000-0002-0484-8522; kinnunen, leena/0000-0001-8739-4812; mangino,
massimo/0000-0002-2167-7470; Hrabe de Angelis,
Martin/0000-0002-7898-2353; Jun, Goo/0000-0003-0891-0204; Fuchsberger,
Christian/0000-0002-5918-8947; Kim, Yongkang/0000-0002-8837-2620; Locke,
Adam/0000-0001-6227-198X
FU Agency for Science, Technology and Research in Singapore; Austrian
Science Fund (FWF) [J-3401]; MGH Research Scholars Award; NIDDK [R01
DK078616, K24 DK080140, DK098032]; NIH [U01 DK085526, U01 DK085501, U01
DK085524, U01 DK085545, U01 DK085584, U01 DK088389]; Wellcome Trust
[090367, 098381, 090532, 083948, 085475, WT098017, WT064890, WT090532];
MRC [G0601261]; EU (Framework 7) [HEALTH-F4-2007-201413]; Oxford
Biomedical Research Centre; National NIHR Bioresource; Uppsala
University; Uppsala University Hospital; Swedish Research Council;
Swedish Heart-Lung Foundation; Wellcome Trust Study Cohort Wellcome
Trust Functional Genomics Grant [072960/2/03/2]; Wellcome Trust Scottish
Health Informatics Programme (SHIP) [086113/Z/08/Z]; Wellcome Trust;
European Community's Seventh Framework Programme (FP7); National
Institute for Health Research (NIHR) BioResource Clinical Research
Facility and Biomedical Research Centre based at Guy's and St Thomas'
NHS Foundation Trust; King's College London; ERC Advanced Principal
Investigator award; Lundbeck Foundation (Lundbeck Foundation Centre for
Applied Medical Genomics in Personalised Disease Prediction, Prevention
and Care (LuCamp)); Danish Council for Independent Research; Novo
Nordisk Foundation; Academy of Finland [124243, 139635, 129293, 117844,
40758, 211497, 118590, 102318, 123885]; Finnish Heart Foundation;
Finnish Diabetes Foundation; Tekes [1510/31/06, 70103/06, 40058/07];
Commission of the European Community [HEALTH-F2-2007-201681]; US
National Institutes of Health [DK093757, DK072193, DK062370, 1Z01
HG000024]; Finnish Foundation for Cardiovascular Research; hospital
district of Pirkanmaa; hospital district of South Ostrobothnia; hospital
district of Central Finland; National Institute for Health and Welfare;
Finnish Diabetes Association; Ministry of Social Affairs and Health in
Finland; Commission of the European Communities; Directorate C-Public
Health [2004310]; Finland's Slottery Machine Association; Ministry of
Health and Social Affairs [5254]; Finnish Funding Agency for Technology
and Innovation [40058/07]; Nordic Centre of Excellence on 'Systems
biology in controlled dietary interventions and cohort studies, SYSDIET
[070014]; Finnish Diabetes Research Foundation; Yrjo Jahnsson Foundation
[56358]; Sigrid Juselius Foundation; Ministry of Education and Culture
of Finland [627]; Kuopio University Hospital; Finnish Heart Association;
Paivikki and Sakari Sohlberg Foundation; European Commission FP6
Integrated Project (EXGENESIS); City of Kuopio and Social Insurance
Institution of Finland [LSHM-CT-2004-005272]
FX HJN was supported by the Agency for Science, Technology and Research in
Singapore. CF was supported by the Austrian Science Fund (FWF) grant
J-3401. JCF was supported by MGH Research Scholars Award. APM is a
Wellcome Trust Senior Research Fellow in Basic and Biomedical Science.
JBM was supported by NIDDK R01 DK078616 and K24 DK080140. MIM is a
Wellcome Trust Senior Investigator (WT098381); and a National Institute
of Health Research Senior Investigator. CML is a Wellcome Trust Research
Career Development Fellow (086596/Z/08/Z). ALG is a Wellcome Trust
Senior Research Fellow in Basic and Biomedical Science (095010/Z/10/Z).
Funding for the GoT2D and T2D-GENES studies was provided by grants NIH
U01s DK085526, DK085501, DK085524, DK085545, and DK085584 (Multiethnic
Study of Type 2 Diabetes Genes) and DK088389 (Low-Pass Sequencing and
High-Density SNP Genotyping for Type 2 Diabetes). Analysis and
genotyping of the British UK cohorts was supported by Wellcome Trust
funding 090367, 098381, 090532, 083948, 085475, MRC (G0601261), EU
(Framework 7) HEALTH-F4-2007-201413, and NIDDK DK098032. The Oxford
Biobank is supported by the Oxford Biomedical Research Centre and part
of the National NIHR Bioresource. The PIVUS/ULSAM cohort was supported
by Wellcome Trust Grants WT098017, WT064890, WT090532, Uppsala
University, Uppsala University Hospital, the Swedish Research Council
and the Swedish Heart-Lung Foundation. GoDARTS study was funded by The
Wellcome Trust Study Cohort Wellcome Trust Functional Genomics Grant
(2004-2008) (Grant No: 072960/2/03/2) and The Wellcome Trust Scottish
Health Informatics Programme (SHIP) (2009-2012) (Grant No:
086113/Z/08/Z). TwinsUK study was funded by the Wellcome Trust; European
Community's Seventh Framework Programme (FP7/2007-2013). The study also
receives support from the National Institute for Health Research (NIHR)
BioResource Clinical Research Facility and Biomedical Research Centre
based at Guy's and St Thomas' NHS Foundation Trust and King's College
London. TDS is holder of an ERC Advanced Principal Investigator award.
The Danish studies were supported by the Lundbeck Foundation (Lundbeck
Foundation Centre for Applied Medical Genomics in Personalised Disease
Prediction, Prevention and Care (LuCamp); http://www.lucamp.org/) and
the Danish Council for Independent Research. The Novo Nordisk Foundation
Center for Basic Metabolic Research is an independent Research Center at
the University of Copenhagen, partially funded by an unrestricted
donation from the Novo Nordisk Foundation (http://www.metabol.ku.dk/).
The METSIM study was supported by the Academy of Finland (contract
124243), the Finnish Heart Foundation, the Finnish Diabetes Foundation,
Tekes (contract 1510/31/06), and the Commission of the European
Community (HEALTH-F2-2007-201681), and the US National Institutes of
Health grants DK093757, DK072193, DK062370, and 1Z01 HG000024. The
FUSION study was supported by DK093757, DK072193, DK062370, and 1Z01
HG000024. Genotyping of the METSIM and DPS studies was conducted at the
Genetic Resources Core Facility (GRCF) at the Johns Hopkins Institute of
Genetic Medicine. VS is funded by the Finnish Foundation for
Cardiovascular Research and the Academy of Finland (grant # 139635).;
The FIN-D2D 2007 study has been financially supported by the hospital
districts of Pirkanmaa, South Ostrobothnia, and Central Finland, the
Finnish National Public Health Institute (current National Institute for
Health and Welfare), the Finnish Diabetes Association, the Ministry of
Social Affairs and Health in Finland, the Academy of Finland (grant
number 129293), Commission of the European Communities, Directorate
C-Public Health (grant agreement no. 2004310) and Finland's Slottery
Machine Association. The DPS has been financially supported by grants
from the Academy of Finland (117844 and 40758, 211497, and 118590 (MU);
The EVO funding of the Kuopio University Hospital from Ministry of
Health and Social Affairs (5254), Finnish Funding Agency for Technology
and Innovation (40058/07), Nordic Centre of Excellence on 'Systems
biology in controlled dietary interventions and cohort studies, SYSDIET
(070014), The Finnish Diabetes Research Foundation, Yrjo Jahnsson
Foundation (56358), Sigrid Juselius Foundation and TEKES grants 70103/06
and 40058/07. The DR's EXTRA Study was supported by grants to RR by the
Ministry of Education and Culture of Finland (627; 2004-2011), Academy
of Finland (102318; 123885), Kuopio University Hospital, Finnish
Diabetes Association, Finnish Heart Association, Paivikki and Sakari
Sohlberg Foundation and by grants from European Commission FP6
Integrated Project (EXGENESIS); LSHM-CT-2004-005272, City of Kuopio and
Social Insurance Institution of Finland (4/26/2010). The Broad Genomics
Platform for genotyping of the FIN-D2D 2007, FINRISK 2007, DR'sEXTRA,
FUSION, and PPP studies. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 21
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U1 2
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JAN
PY 2015
VL 11
IS 1
AR e1004876
DI 10.1371/journal.pgen.1004876
PG 25
WC Genetics & Heredity
SC Genetics & Heredity
GA CB0KL
UT WOS:000349314600012
PM 25625282
ER
PT J
AU Rattray, A
Santoyo, G
Shafer, B
Strathern, JN
AF Rattray, Alison
Santoyo, Gustavo
Shafer, Brenda
Strathern, Jeffrey N.
TI Elevated Mutation Rate during Meiosis in Saccharomyces cerevisiae
SO PLOS GENETICS
LA English
DT Article
ID DOUBLE-STRAND-BREAK; MEIOTIC RECOMBINATION; GENE CONVERSION; CROSSOVER
INTERFERENCE; ADAPTIVE MUTATION; DNA-POLYMERASE; CHROMOSOME-III; YEAST;
REPAIR; MUTAGENESIS
AB Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis. Since the process of meiosis involves many programmed DSBs, we reasoned that this repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel observed elevated reversion of recessive alleles during meiosis, and found that the revertants were more likely to be associated with a crossover than non-revertants, a process that they called "the meiotic effect." Here we use a forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination coldspot or hotspot near the MAT locus on Chromosome III. We find that the increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying recombination rate at the locus. Importantly, we show that the elevated mutation rate is fully dependent upon Spo11, the protein that introduces the meiosis specific DSBs. To examine associated recombination we selected for random spores with or without a mutation in CAN1. We find that the mutations isolated this way show an increased association with recombination (crossovers, loss of crossover interference and/or increased gene conversion tracts). Polf appears to contribute about half of the mutations induced during meiosis, but is not the only source of mutations for the meiotic effect. We see no difference in either the spectrum or distribution of mutations between mitosis and meiosis. The correlation of hotspots with elevated mutagenesis provides a mechanism for organisms to control evolution rates in a gene specific manner.
C1 [Rattray, Alison; Santoyo, Gustavo; Shafer, Brenda; Strathern, Jeffrey N.] NCI Frederick, Gene Regulat & Chromosome Biol Lab, FNLCR, Frederick, MD 21702 USA.
RP Rattray, A (reprint author), NCI Frederick, Gene Regulat & Chromosome Biol Lab, FNLCR, Frederick, MD 21702 USA.
EM stratherj@mail.nih.gov
OI Santoyo, Gustavo/0000-0002-0374-9661
FU Intramural program of the National Cancer Institute
FX Funding was provided by the Intramural program of the National Cancer
Institute. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 67
TC 11
Z9 11
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JAN
PY 2015
VL 11
IS 1
AR e1004910
DI 10.1371/journal.pgen.1004910
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA CB0KL
UT WOS:000349314600030
PM 25569256
ER
PT J
AU Shakhova, O
Cheng, P
Mishra, PJ
Zingg, D
Schaefer, SM
Debbache, J
Hausel, J
Matter, C
Guo, T
Davis, S
Meltzer, P
Mihic-Probst, D
Moch, H
Wegner, M
Merlino, G
Levesque, MP
Dummer, R
Santoro, R
Cinelli, P
Sommer, L
AF Shakhova, Olga
Cheng, Phil
Mishra, Pravin J.
Zingg, Daniel
Schaefer, Simon M.
Debbache, Julien
Haeusel, Jessica
Matter, Claudia
Guo, Theresa
Davis, Sean
Meltzer, Paul
Mihic-Probst, Daniela
Moch, Holger
Wegner, Michael
Merlino, Glenn
Levesque, Mitchell P.
Dummer, Reinhard
Santoro, Raffaella
Cinelli, Paolo
Sommer, Lukas
TI Antagonistic Cross-Regulation between Sox9 and Sox10 Controls an
Anti-tumorigenic Program in Melanoma
SO PLOS GENETICS
LA English
DT Article
ID TRANSCRIPTION FACTOR SOX10; CREST-DERIVED MELANOCYTES; CELL LUNG-CANCER;
NEURAL CREST; HIRSCHSPRUNG-DISEASE; MOUSE MODEL; CAMPOMELIC DYSPLASIA;
SPINAL-CORD; STEM-CELLS; EXPRESSION
AB Melanoma is the most fatal skin cancer, but the etiology of this devastating disease is still poorly understood. Recently, the transcription factor Sox10 has been shown to promote both melanoma initiation and progression. Reducing SOX10 expression levels in human melanoma cells and in a genetic melanoma mouse model, efficiently abolishes tumorigenesis by inducing cell cycle exit and apoptosis. Here, we show that this anti-tumorigenic effect functionally involves SOX9, a factor related to SOX10 and upregulated in melanoma cells upon loss of SOX10. Unlike SOX10, SOX9 is not required for normal melanocyte stem cell function, the formation of hyperplastic lesions, and melanoma initiation. To the contrary, SOX9 overexpression results in cell cycle arrest, apoptosis, and a gene expression profile shared by melanoma cells with reduced SOX10 expression. Moreover, SOX9 binds to the SOX10 promoter and induces downregulation of SOX10 expression, revealing a feedback loop reinforcing the SOX10 low/SOX9 high ant, m/ii-tumorigenic program. Finally, SOX9 is required in vitro and in vivo for the anti-tumorigenic effect achieved by reducing SOX10 expression. Thus, SOX10 and SOX9 are functionally antagonistic regulators of melanoma development.
C1 [Shakhova, Olga; Zingg, Daniel; Schaefer, Simon M.; Debbache, Julien; Haeusel, Jessica; Sommer, Lukas] Univ Zurich, Inst Anat, Zurich, Switzerland.
[Cheng, Phil; Levesque, Mitchell P.; Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
[Mishra, Pravin J.; Guo, Theresa; Davis, Sean; Meltzer, Paul; Merlino, Glenn] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Mihic-Probst, Daniela; Moch, Holger] Univ Zurich Hosp, Inst Surg Pathol, Dept Pathol, CH-8091 Zurich, Switzerland.
[Wegner, Michael] FAU Univ Erlangen Nuernberg, Inst Biochem, Emil Fischer Ctr, Erlangen, Germany.
[Santoro, Raffaella] Univ Zurich, Inst Vet Biochem & Mol Biol, Zurich, Switzerland.
[Cinelli, Paolo] Univ Zurich Hosp, Clin Res Ctr, Div Trauma Surg, CH-8091 Zurich, Switzerland.
[Shakhova, Olga; Matter, Claudia] Univ Zurich Hosp, Dept Oncol, Schlieren, Switzerland.
RP Shakhova, O (reprint author), Univ Zurich Hosp, Dept Oncol, Schlieren, Switzerland.
EM lukas.sommer@anatom.uzh.ch
RI Santoro, Raffaella/L-2637-2013;
OI Davis, Sean/0000-0002-8991-6458; Zingg, Daniel/0000-0001-6450-2534;
Wegner, Michael/0000-0002-4586-3294
FU Swiss National Science Foundation; National Research Program [NRP-63];
Swiss Cancer League; UBS-Promedica Stiftung; University Research
Priority Program (URPP) of the University of Zurich
FX This work was supported by the Swiss National Science Foundation, the
National Research Program (NRP-63) "Stem Cells and Regenerative
Medicine", the Swiss Cancer League, the UBS-Promedica Stiftung, and the
University Research Priority Program (URPP) "Translational Cancer
Research" of the University of Zurich. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 62
TC 12
Z9 13
U1 2
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JAN
PY 2015
VL 11
IS 1
AR e1004877
DI 10.1371/journal.pgen.1004877
PG 21
WC Genetics & Heredity
SC Genetics & Heredity
GA CB0KL
UT WOS:000349314600013
PM 25629959
ER
PT J
AU Su, D
Wang, XT
Campbell, MR
Song, LY
Safi, A
Crawford, GE
Bell, DA
AF Su, Dan
Wang, Xuting
Campbell, Michelle R.
Song, Lingyun
Safi, Alexias
Crawford, Gregory E.
Bell, Douglas A.
TI Interactions of Chromatin Context, Binding Site Sequence Content, and
Sequence Evolution in Stress-Induced p53 Occupancy and Transactivation
SO PLOS GENETICS
LA English
DT Article
ID TRANSCRIPTION-FACTOR-BINDING; EMBRYONIC STEM-CELLS; HUMAN GENOME;
REGULATORY ELEMENTS; RESPONSE ELEMENT; GENE-EXPRESSION; TARGET GENES;
DNA-DAMAGE; IDENTIFICATION; PATTERNS
AB Cellular stresses activate the tumor suppressor p53 protein leading to selective binding to DNA response elements (REs) and gene transactivation from a large pool of potential p53 REs (p53REs). To elucidate how p53RE sequences and local chromatin context interact to affect p53 binding and gene transactivation, we mapped genome-wide binding localizations of p53 and H3K4me3 in untreated and doxorubicin (DXR)-treated human lymphoblastoid cells. We examined the relationships among p53 occupancy, gene expression, H3K4me3, chromatin accessibility (DNase 1 hypersensitivity, DHS), ENCODE chromatin states, p53RE sequence, and evolutionary conservation. We observed that the inducible expression of p53-regulated genes was associated with the steady-state chromatin status of the cell. Most highly inducible p53-regulated genes were suppressed at baseline and marked by repressive histone modifications or displayed CTCF binding. Comparison of p53RE sequences residing in different chromatin contexts demonstrated that weaker p53REs resided in open promoters, while stronger p53REs were located within enhancers and repressed chromatin. p53 occupancy was strongly correlated with similarity of the target DNA sequences to the p53RE consensus, but surprisingly, inversely correlated with pre-existing nucleosome accessibility (DHS) and evolutionary conservation at the p53RE. Occupancy by p53 of REs that overlapped transposable element (TE) repeats was significantly higher (p<10(-7)) and correlated with stronger p53RE sequences (p<10(-110)) relative to nonTE-associated p53REs, particularly for MLT1H, LTR10B, and Mer61 TEs. However, binding at these elements was generally not associated with transactivation of adjacent genes. Occupied p53REs located in L2-like TEs were unique in displaying highly negative PhyloP scores (predicted fast-evolving) and being associated with altered H3K4me3 and DHS levels. These results underscore the systematic interaction between chromatin status and p53RE context in the induced transactivation response. This p53 regulated response appears to have been tuned via evolutionary processes that may have led to repression and/or utilization of p53REs originating from primate-specific transposon elements.
C1 [Su, Dan; Wang, Xuting; Campbell, Michelle R.; Bell, Douglas A.] NIEHS, Environm Genom Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC USA.
[Song, Lingyun; Safi, Alexias; Crawford, Gregory E.] Duke Univ, Inst Genome Sci & Policy, Durham, NC USA.
RP Su, D (reprint author), NIEHS, Environm Genom Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC USA.
EM BELL1@niehs.nih.gov
OI Wang, Xuting/0000-0001-6781-8008
FU Intramural Research Program of National Institute of Environmental
Health Sciences-National Institutes of Health [ZO1ES100475]
FX This work was funded by the Intramural Research Program of National
Institute of Environmental Health Sciences-National Institutes of
Health, ZO1ES100475 to DAB. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 63
TC 12
Z9 12
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JAN
PY 2015
VL 11
IS 1
AR e1004885
DI 10.1371/journal.pgen.1004885
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA CB0KL
UT WOS:000349314600014
PM 25569532
ER
PT J
AU Elmore, SA
Cora, MC
Gruebbel, MM
Hayes, SA
Hoane, JS
Koizumi, H
Peters, R
Rosol, TJ
Singh, BP
Szabo, KA
AF Elmore, Susan A.
Cora, Michelle C.
Gruebbel, Margarita M.
Hayes, Schantel A.
Hoane, Jessica S.
Koizumi, Haruko
Peters, Rachel
Rosol, Thomas J.
Singh, Bhanu P.
Szabo, Kathleen A.
TI Proceedings of the 2014 National Toxicology Program Satellite Symposium
SO TOXICOLOGIC PATHOLOGY
LA English
DT Review
DE NTP Satellite Symposium; mucinous adenoma; plexiform vasculopathy;
vaginal cytology; chronic-active pancreatitis; retinal dysplasia;
thymoma; mesenteric lymph node angiomatous lesion; fovea cyst; endocrine
nomenclature; acute tumor lysis syndrome
ID INDUCED VASCULAR INJURY; SPRAGUE-DAWLEY RATS; HANNOVER GALAS RATS;
SPONTANEOUS THYMOMA RATS; GOBLET CELL METAPLASIA; INHIBITOR SCH 351591;
TUMOR LYSIS SYNDROME; CONTROL WISTAR RATS; ESTROUS-CYCLE; 2-YEAR
CARCINOGENICITY
AB The 2014 annual National Toxicology Program (NTP) Satellite Symposium, entitled Pathology Potpourri was held in Washington, D.C., in advance of the Society of Toxicologic Pathology's 33rd annual meeting. The goal of this annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a pulmonary mucinous adenocarcinoma in a male B6C3F1 mouse; plexiform vasculopathy in Wistar Han (Crl:WI[Han]) rats; staging of the estrous cycle in rats and mice; peri-islet fibrosis, hemorrhage, lobular atrophy and inflammation in male Sprague-Dawley (SD) rats; retinal dysplasia in Crl:WI[Han] rats and B6C3F1 mice; multicentric lymphoma with intravascular microemboli and tumor lysis syndrome, and 2 cases of myopathy and vascular anomaly in Tg.rasH2 mice; benign thymomas in Crl:WI[Han] rats; angiomatous lesions in the mesenteric lymph nodes of Crl:WI[Han] rats; an unusual foveal lesion in a cynomolgous monkey; and finally a series of nomenclatures challenges from the endocrine International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) Organ Working Group (OWG).
C1 [Elmore, Susan A.; Cora, Michelle C.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Gruebbel, Margarita M.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
[Hayes, Schantel A.; Hoane, Jessica S.; Szabo, Kathleen A.] Pathol Associates Inc, Charles River Labs, Durham, NC USA.
[Koizumi, Haruko] Ina Res Inc, Nagano, Japan.
[Peters, Rachel] Takeda Pharmaceut Int Co, Cambridge, MA USA.
[Rosol, Thomas J.] Ohio State Univ, Columbus, OH 43210 USA.
[Singh, Bhanu P.] Janssen Res & Dev, Spring House, PA USA.
RP Elmore, SA (reprint author), NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
EM elmore@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Environmental Health Sciences (NIEHS)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported, in part, by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS).
NR 124
TC 2
Z9 2
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JAN
PY 2015
VL 43
IS 1
BP 10
EP 40
DI 10.1177/0192623314555526
PG 31
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CA4ZT
UT WOS:000348917300001
PM 25385331
ER
PT J
AU Morrison, JP
Sharma, AK
Rao, D
Pardo, ID
Garman, RH
Kaufmann, W
Bolon, B
AF Morrison, James P.
Sharma, Alok K.
Rao, Deepa
Pardo, Ingrid D.
Garman, Robert H.
Kaufmann, Wolfgang
Bolon, Brad
TI Fundamentals of Translational Neuroscience in Toxicologic Pathology:
Optimizing the Value of Animal Data for Human Risk Assessment
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE nervous system; neuroanatomy; neuropathology; neurotoxicity;
neuroscience; translational medicine; PEGylation
ID NONCLINICAL GENERAL TOXICITY; MAGNETIC-RESONANCE HISTOLOGY; HUMAN
CEREBRAL-CORTEX; NERVOUS-SYSTEM; DEVELOPMENTAL NEUROTOXICITY;
NEUROPATHOLOGY ASSESSMENT; SPECIES-DIFFERENCES; CORPUS-CALLOSUM;
TECHNICAL GUIDE; MOUSE STRAINS
AB A half-day Society of Toxicologic Pathology continuing education course on Fundamentals of Translational Neuroscience in Toxicologic Pathology presented some current major issues faced when extrapolating animal data regarding potential neurological consequences to assess potential human outcomes. Two talks reviewed functional-structural correlates in rodent and nonrodent mammalian brains needed to predict behavioral consequences of morphologic changes in discrete neural cell populations. The third lecture described practical steps for ensuring that specimens from rodent developmental neurotoxicity tests will be processed correctly to produce highly homologous sections. The fourth talk detailed demographic factors (e.g., species, strain, sex, and age); physiological traits (body composition, brain circulation, pharmacokinetic/pharmacodynamic patterns, etc.); and husbandry influences (e.g., group housing) known to alter the effects of neuroactive agents. The last presentation discussed the appearance, unknown functional effects, and potential relevance to humans of polyethylene glycol (PEG)-associated vacuoles within the choroid plexus epithelium of animals. Speakers provided real-world examples of challenges with data extrapolation among species or with study design considerations that may impact the interpretability of results. Translational neuroscience will be bolstered in the future as less invasive and/or more quantitative techniques are devised for linking overt functional deficits to subtle anatomic and chemical lesions.
C1 [Morrison, James P.] Charles River Pathol Associates, Durham, NC USA.
[Sharma, Alok K.] Covance Inc, Madison, WI USA.
[Rao, Deepa] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Rao, Deepa] Integrated Syst Lab, Res Triangle Pk, NC USA.
[Pardo, Ingrid D.] Pfizer Inc, Groton, CT 06340 USA.
[Garman, Robert H.] Consultants Vet Pathol Inc, Murrysville, PA USA.
[Kaufmann, Wolfgang] Merck KGaA, Darmstadt, Germany.
[Bolon, Brad] Ohio State Univ, Coll Vet Med, Columbus, OH 43210 USA.
RP Bolon, B (reprint author), Ohio State Univ, 1900 Coffey Rd,450 VMAB, Columbus, OH 43210 USA.
EM bolon.15@osu.edu
FU Society of Toxicologic Pathology's (STP) Annual Symposium Committee;
Continuing Education Sub-Committee; Scientific Program Planning
Committee
FX The authors thank the Society of Toxicologic Pathology's (STP) Annual
Symposium Committee, the Continuing Education Sub-Committee, and the
Scientific Program Planning Committee for their support of this program.
We would also like to thank the staff of the STP for organizational
support in producing the materials and arranging the meeting space and
Steve Van Adestine of Covance Laboratories Inc. for assisting with the
figures.
NR 85
TC 1
Z9 1
U1 1
U2 11
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JAN
PY 2015
VL 43
IS 1
BP 132
EP 139
DI 10.1177/0192623314558306
PG 8
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CA4ZT
UT WOS:000348917300014
PM 25398755
ER
PT J
AU Gowdy, KM
Martinu, T
Nugent, JL
Manzo, ND
Zhang, HL
Kelly, FL
Holtzman, MJ
Palmer, SM
AF Gowdy, Kymberly M.
Martinu, Tereza
Nugent, Julia L.
Manzo, Nicholas D.
Zhang, Helen L.
Kelly, Francine L.
Holtzman, Michael J.
Palmer, Scott M.
TI Impaired CD8(+) T cell immunity after allogeneic bone marrow
transplantation leads to persistent and severe respiratory viral
infection
SO TRANSPLANT IMMUNOLOGY
LA English
DT Article
DE Bone marrow transplant; Respiratory virus; Lung; CD8(+) T cells
ID HEMATOPOIETIC STEM-CELL; INFLUENZA-VIRUS INFECTION; VERSUS-HOST-DISEASE;
SENDAI-VIRUS; PSEUDOMONAS-AERUGINOSA; PROTECTIVE IMMUNITY; MEMORY;
RECIPIENTS; CLEARANCE; MICE
AB Rationale: Bone marrow transplant (BMT) recipients experience frequent and severe respiratory viral infections (RVIs). However, the immunological mechanisms predisposing to RVIs are uncertain. Therefore, we hypothesized that antiviral T cell immunity is impaired as a consequence of allogeneic BMT, independent of pharmacologic immunosuppression, and is responsible for increased susceptibility to RVI.
Methods: Bone marrow and splenocytes from C57BL/6(H2(b)) mice were transplanted into B10.BR(H2(k)) (Allo) or C57BL/6(H2(b)) (Syn) recipients. Five weeks after transplantation, recipient mice were inoculated intranasally with mouse parainfluenza virus type 1 (mPIV-1), commonly known as Sendai virus (SeV), and monitored for relevant immunological and disease endpoints.
Main results: Severe and persistent airway inflammation, epithelial injury, and enhanced mortality are found after viral infection in Allo mice but not in control Syn and non-transplanted mice. In addition, viral clearance is delayed in Allo mice as evidenced by prolonged detection of viral transcripts at Day 15 post-inoculation (p.i.) but not in control mice. In concert with these events, we also detected decreased levels of total and virus-specific CD8(+) T cells, as well as increased T cellexpression of inhibitory receptor programmed death-1 (PD-1), in the lungs of Allo mice at Day 8 p.i. Adoptive transfer of CD8(+) T cells from non-transplanted mice recovered from SeV infection into Alio mice at Day 8 p.i. restored normal levels of viral clearance, epithelial repair, and lung inflammation.
Conclusions: Taken together these results indicate that allogeneic BMT results in more severe RVI based on the failure to develop an appropriate pulmonary CD8(+) T cell response, providing an important potential mechanism to target in improving outcomes of RVI after BMT. Published by Elsevier B.V.
C1 [Gowdy, Kymberly M.; Martinu, Tereza; Nugent, Julia L.; Manzo, Nicholas D.; Zhang, Helen L.; Kelly, Francine L.; Palmer, Scott M.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Holtzman, Michael J.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Palmer, Scott M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
RP Gowdy, KM (reprint author), NIEHS, LRB, 111 TW Alexander Dr,Bldg 101,Mail Drop, Res Triangle Pk, NC 27709 USA.
EM kymberly.gowdy@nih.gov
FU NIH/NHLBI [1P50-HL084917-01 (SCCOR)]; Project 3; NIH [1 K24 HL91140-01]
FX NIH/NHLBI 1P50-HL084917-01 (SCCOR), Project 3 (SMP), Training core (to
KG and TM), NIH 1 K24 HL91140-01 (SMP).
NR 52
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0966-3274
EI 2210-3384
J9 TRANSPL IMMUNOL
JI Transpl. Immunol.
PD JAN
PY 2015
VL 32
IS 1
BP 51
EP 60
DI 10.1016/j.trim.2014.10.005
PG 10
WC Immunology; Transplantation
SC Immunology; Transplantation
GA CA4RT
UT WOS:000348892900009
PM 25446809
ER
PT J
AU Montgomery, DC
Sorum, AW
Meier, JL
AF Montgomery, David C.
Sorum, Alexander W.
Meier, Jordan L.
TI Defining the Orphan Functions of Lysine Acetyltransferases
SO ACS CHEMICAL BIOLOGY
LA English
DT Review
ID PYRUVATE-DEHYDROGENASE COMPLEX; SMALL-MOLECULE INHIBITOR; HISTONE
ACETYLTRANSFERASE; TRANSFER-RNA; SACCHAROMYCES-CEREVISIAE; PROTEIN
ACETYLATION; ELONGATOR COMPLEX; ALPHA-TUBULIN; TRANSCRIPTIONAL
COACTIVATOR; MITOCHONDRIAL PROTEIN
AB Long known for their role in histone acetylation, recent studies have demonstrated that lysine acetyltransferases also carry out distinct orphan functions. These activities impact a wide range of biological phenomena including metabolism, RNA modification, nuclear morphology, and mitochondrial function. Here, we review the discovery and characterization of orphan lysine acetyltransferase functions. In addition to highlighting the evidence and biological role for these functions in human disease, we discuss the part emerging chemical tools may play in investigating this versatile enzyme superfamily.
C1 [Montgomery, David C.; Sorum, Alexander W.; Meier, Jordan L.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
RP Meier, JL (reprint author), NCI, Biol Chem Lab, Frederick, MD 21702 USA.
EM jordan.meier@nih.gov
RI Meier, Jordan/N-2608-2014
NR 94
TC 8
Z9 8
U1 1
U2 16
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD JAN
PY 2015
VL 10
IS 1
BP 85
EP 94
DI 10.1021/cb500853p
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AZ6LU
UT WOS:000348332100008
PM 25591746
ER
PT J
AU Kiyatkin, EA
Wakabayashi, KT
AF Kiyatkin, Eugene A.
Wakabayashi, Ken T.
TI Parsing Glucose Entry into the Brain: Novel Findings Obtained with
Enzyme-Based Glucose Biosensors
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Review
DE Brain metabolism; amperometry; enzyme-based glucose sensors; neuronal
activity; metabolic brain activation; cerebral blood flow
ID FREELY-MOVING RATS; NATURAL AROUSING STIMULI; NUCLEUS-ACCUMBENS SHELL;
EXTRACELLULAR GLUCOSE; INTRAVENOUS COCAINE; NEURONAL-ACTIVITY;
SUBSTANTIA-NIGRA; RAPID CHANGES; PHYSIOLOGICAL FLUCTUATIONS; RETICULATA
NEURONS
AB Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.
C1 [Kiyatkin, Eugene A.; Wakabayashi, Ken T.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU National Institute on Drug Abuse Intramural Research Program, NIH
FX Supported by the National Institute on Drug Abuse Intramural Research
Program, NIH.
NR 60
TC 6
Z9 6
U1 1
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JAN
PY 2015
VL 6
IS 1
BP 108
EP 116
DI 10.1021/cn5002304
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA AZ6ON
UT WOS:000348338900013
PM 25490002
ER
PT J
AU Zhao, HY
Schuck, P
AF Zhao, Huaying
Schuck, Peter
TI Combining biophysical methods for the analysis of protein complex
stoichiometry and affinity in SEDPHAT
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
DE GMMA; SEDPHAT
ID ISOTHERMAL TITRATION CALORIMETRY; FLUORESCENCE-DETECTED SEDIMENTATION;
SURFACE-PLASMON RESONANCE; VELOCITY ANALYTICAL ULTRACENTRIFUGATION;
MASS-TRANSPORT LIMITATION; LAMM EQUATION; COOPERATIVE INTERACTIONS;
BINDING CONSTANTS; GLOBAL ANALYSIS; LIGAND-BINDING
AB Reversible macromolecular interactions are ubiquitous in signal transduction pathways, often forming dynamic multi-protein complexes with three or more components. Multivalent binding and cooperativity in these complexes are often key motifs of their biological mechanisms. Traditional solution biophysical techniques for characterizing the binding and cooperativity are very limited in the number of states that can be resolved. A global multi-method analysis (GMMA) approach has recently been introduced that can leverage the strengths and the different observables of different techniques to improve the accuracy of the resulting binding parameters and to facilitate the study of multi-component systems and multi-site interactions. Here, GMMA is described in the software SEDPHAT for the analysis of data from isothermal titration calorimetry, surface plasmon resonance or other biosensing, analytical ultracentrifugation, fluorescence anisotropy and various other spectroscopic and thermodynamic techniques. The basic principles of these techniques are reviewed and recent advances in view of their particular strengths in the context of GMMA are described. Furthermore, a new feature in SEDPHAT is introduced for the simulation of multi-method data. In combination with specific statistical tools for GMMA in SEDPHAT, simulations can be a valuable step in the experimental design.
C1 [Zhao, Huaying; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Zhao, HY (reprint author), Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
EM zhaoh3@mail.nih.gov; schuckp@mail.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Institute of Biomedical Imaging and Bioengineering, National
Institutes of Health.
NR 71
TC 8
Z9 8
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1399-0047
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD JAN
PY 2015
VL 71
SI SI
BP 3
EP 14
DI 10.1107/S1399004714010372
PN 1
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA AZ9WE
UT WOS:000348563900002
PM 25615855
ER
PT J
AU Kris-Etherton, PM
Akabas, SR
Douglas, P
Kohlmeier, M
Laur, C
Lenders, CM
Levy, MD
Nowson, C
Ray, S
Pratt, CA
Seidner, DL
Saltzman, E
AF Kris-Etherton, Penny M.
Akabas, Sharon R.
Douglas, Pauline
Kohlmeier, Martin
Laur, Celia
Lenders, Carine M.
Levy, Matthew D.
Nowson, Caryl
Ray, Sumantra
Pratt, Charlotte A.
Seidner, Douglas L.
Saltzman, Edward
TI Nutrition Competencies in Health Professionals' Education and Training:
A New Paradigm
SO ADVANCES IN NUTRITION
LA English
DT Editorial Material
DE health professional; inter-professional; nutrition; nutrition education;
competency-based education; health policy
ID CLINICAL-OUTCOMES; CARE; CALL
AB Most health care professionals are not adequately trained to address diet and nutrition-related issues with their patients, thus missing important opportunities to ameliorate chronic diseases and improve outcomes in acute illness. In this symposium, the speakers reviewed the status of nutrition education for health care professionals in the United States, United Kingdom, and Australia. Nutrition education is not required for educating and training physicians in many countries. Nutrition education for the spectrum of health care professionals is uncoordinated, which runs contrary to the current theme of interprofessional education. The central role of competencies in guiding medical education was emphasized and the urgent need to establish competencies in nutrition-related patient care was presented. The importance of additional strategies to improve nutrition education of health care professionals was highlighted. Public health legislation such as the Patient Protection and Affordable Care Act recognizes the role of nutrition, however, to capitalize on this increasing momentum, health care professionals must be trained to deliver needed services. Thus, there is a pressing need to garner support from stakeholders to achieve this goal. Promoting a research agenda that provides outcome-based evidence on individual and public health levels is needed to improve and sustain effective interprofessional nutrition education.
C1 [Kris-Etherton, Penny M.] Penn State Univ, University Pk, PA 16802 USA.
[Akabas, Sharon R.] Columbia Univ, New York, NY USA.
[Douglas, Pauline] Univ Ulster, Coleraine BT52 1SA, Londonderry, North Ireland.
[Kohlmeier, Martin] UNC Sch Med & Publ Hlth, Chapel Hill, NC USA.
[Kohlmeier, Martin] UNC Nutr Res Inst, Chapel Hill, NC USA.
[Laur, Celia; Ray, Sumantra] UK Med Res Council, Human Nutr Res Unit, Cambridge, England.
[Lenders, Carine M.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Levy, Matthew D.] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Levy, Matthew D.] Bipartisan Policy Ctr, University Pk, PA USA.
[Nowson, Caryl] Deakin Univ, Sch Exercise & Nutr Sci, Geelong, Vic 3217, Australia.
[Pratt, Charlotte A.] NIH, Bethesda, MD 20892 USA.
[Seidner, Douglas L.] Vanderbilt Univ, Med Ctr, Nashville, TN 37235 USA.
[Saltzman, Edward] Tufts Univ, Boston, MA 02111 USA.
RP Kris-Etherton, PM (reprint author), Penn State Univ, University Pk, PA 16802 USA.
EM pmk3@psu.edu
FU American Society for Nutrition (ASN); ASN Medical Nutrition Council; ASH
Global Nutrition Council; New Balance Foundation; Boston Nutrition
Obesity Research Center [P30DK46200]; National Institute of Diabetes and
Digestive and Kidney Diseases [5-K23DK082732]; Abbott Fund
FX This article is a summary of the symposium "Nutrition Competencies in
Health Professionals' Education and Training. A New Paradigm" held 27
April 2014 at the ASH Scientific Sessions and Annual Meeting at
Experimental Biology 2014 in San Diego, CA. The symposium was sponsored
by the American Society for Nutrition (ASN), the ASN Medical Nutrition
Council, and the ASH Global Nutrition Council; ASN provided partial
travel support for speakers to attend Experimental Biology 2014. CML
received educational support for this activity from the New Balance
Foundation (www.newbalancefoundation.org), Boston Nutrition Obesity
Research Center (P30DK46200), National Institute of Diabetes and
Digestive and Kidney Diseases (5-K23DK082732). Other support also
includes the Abbott Fund (www.abbottfund.org).
NR 20
TC 7
Z9 7
U1 1
U2 8
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 JAN
PY 2015
VL 6
IS 1
BP 83
EP 87
DI 10.3945/an.114.006734
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AZ8SG
UT WOS:000348484300008
PM 25593146
ER
PT J
AU Dwyer, JT
Wiemer, KL
Dary, O
Keen, CL
King, JC
Miller, KB
Philbert, MA
Tarasuk, V
Taylor, CL
Gaine, PC
Jarvis, AB
Bailey, RL
AF Dwyer, Johanna T.
Wiemer, Kathryn L.
Dary, Omar
Keen, Carl L.
King, Janet C.
Miller, Kevin B.
Philbert, Martin A.
Tarasuk, Valerie
Taylor, Christine L.
Gaine, P. Courtney
Jarvis, Ashley B.
Bailey, Regan L.
TI Fortification and Health: Challenges and Opportunities
SO Advances in Nutrition
LA English
DT Article
DE dietary intake; dietary supplements; folate; folic acid; vitamin B-9
ID CORONARY-ARTERY-DISEASE; USE DIETARY-SUPPLEMENTS; NEURAL-TUBE DEFECTS;
FOOD FORTIFICATION; FOLIC-ACID; PROSPECTIVE COHORT; FLAVONOID INTAKE; US
CHILDREN; NANOPARTICLES; VITAMIN
AB Fortification is the process of adding nutrients or non-nutrient bioactive components to edible products (e.g., food, food constituents, or supplements). Fortification can be used to correct or prevent widespread nutrient intake shortfalls and associated deficiencies, to balance the total nutrient profile of a diet, to restore nutrients lost in processing, or to appeal to consumers looking to supplement their diet. Food fortification could be considered as a public health strategy to enhance nutrient intakes of a population. Over the past century, fortification has been effective at reducing the risk of nutrient deficiency diseases such as beriberi, goiter, pellagra, and rickets. However, the world today is very different from when fortification emerged in the 1920s. Although early fortification programs were designed to eliminate deficiency diseases, current fortification programs are based on low dietary intakes rather than a diagnosable condition. Moving forward, we must be diligent in our approach to achieving effective and responsible fortification practices and policies, including responsible marketing of fortified products. Fortification must be applied prudently, its effects monitored diligently, and the public informed effectively about its benefits through consumer education efforts. Clear lines of authority for establishing fortification guidelines should be developed and should take into account changing population demographics, changes in the food supply, and advances in technology. This article is a summary of a symposium presented at the ASN Scientific Sessions and Annual Meeting at Experimental Biology 2014 on current issues involving fortification focusing primarily on the United States and Canada and recommendations for the development of responsible fortification practices to ensure their safety and effectiveness.
C1 [Dwyer, Johanna T.] Tufts Med Ctr, Boston, MA 02111 USA.
[Wiemer, Kathryn L.; Miller, Kevin B.] Gen Mills Inc, Minneapolis, MN USA.
[Dary, Omar] Bur Global Hlth, Washington, DC USA.
[Keen, Carl L.] Univ Calif Davis, Davis, CA 95616 USA.
[King, Janet C.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Philbert, Martin A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Tarasuk, Valerie] Univ Toronto, Toronto, ON, Canada.
[Taylor, Christine L.; Bailey, Regan L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Jarvis, Ashley B.] ILSI North Amer, Washington, DC USA.
RP Dwyer, JT (reprint author), Tufts Med Ctr, Boston, MA 02111 USA.
EM jciwyer1@tuftsmedicalcenter.org
OI Dwyer, Johanna/0000-0002-0783-1769
FU American Society for Nutrition (ASN); International Life Sciences
Institute (LSI), North America; ILSI North America Committee on
Fortification
FX This article is the result of presentations at the symposium
"Fortification and Health: Opportunities and Challenges" held 26 April
2014 at the ASN Scientific Sessions and Annual Meeting at Experimental
Biology 2014 in San Diego, CA The symposium was sponsored by the
American Society for Nutrition (ASN) and the International Life Sciences
Institute (LSI), North America; Supported by the ILSI North America
Committee on Fortification. Detailed information about the group can be
found at http://www.ilsi.org/NorthAmerica/Pages/Fortification.aspx. ILSI
North America is a public, nonprofit foundation that provides a forum to
advance understanding of scientific issues related to the nutntional
quality and safety of the food supply by sponsoring research programs,
educational seminars and workshops, and publications. !LSI North America
receives support primarily from its industry membership, which works
collaboratively with academic scientific advisors on the development of
its programs Science writer Densie Webb, PhD, RD, contributed to
development of drafts of this article and received funds from the ILSI
North America Committee on Fortification. This is a free access article,
distributed under terms
(http://www.nutritionorg/publications/guidelines-and-policies/license/)
that permit unrestricted noncommercial use, distribution, and
reproduction in any medium, provided the original work is properly
cited.
NR 69
TC 6
Z9 6
U1 4
U2 36
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 JAN
PY 2015
VL 6
IS 1
BP 124
EP 131
DI 10.3945/an.114.007443
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AZ8SG
UT WOS:000348484300013
PM 25593151
ER
PT J
AU Newport, MT
VanItallie, TB
Kashiwaya, Y
King, MT
Veech, RL
AF Newport, Mary T.
VanItallie, Theodore B.
Kashiwaya, Yoshihiro
King, Michael Todd
Veech, Richard L.
TI A new way to produce hyperketonemia: Use of ketone ester in a case of
Alzheimer's disease
SO Alzheimers & Dementia
LA English
DT Article
DE Ketone bodies; beta-Hydroxybutyrate; Pyruvate dehydrogenase; Brain
insulin resistance; Fasting; Ketogenic diet; Medium-chain triglyceride;
Ketone monoester
ID BRAIN INSULIN-RESISTANCE; (R)-3-HYDROXYBUTYL (R)-3-HYDROXYBUTYRATE;
KETOGENIC DIET; METABOLISM; BODIES; MILD
AB Background: Providing ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the <= 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches.
Method: Described herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent-ketone monoester (KME)-to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12.
Results: The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma beta-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels.
Conclusion: KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet. Published by Elsevier Inc. on behalf of The Alzheimer's Association.
C1 [Newport, Mary T.] Spring Hill Neonatol Inc, Spring Hill, FL USA.
[VanItallie, Theodore B.] St Lukes Hosp, Dept Med, New York, NY USA.
[Kashiwaya, Yoshihiro] Tominaga Hosp, Div Neurol, Osaka, Japan.
[King, Michael Todd; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA.
RP Veech, RL (reprint author), NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA.
EM rlveech@comcast.net
FU Intramural NIH HHS [Z01 AA000110-10]
NR 23
TC 16
Z9 16
U1 6
U2 24
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 JAN
PY 2015
VL 11
IS 1
BP 99
EP 103
DI 10.1016/j.jalz.2014.01.006
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA CA0UX
UT WOS:000348632800009
PM 25301680
ER
PT J
AU Scheidweiler, KB
Jarvis, MJY
Huestis, MA
AF Scheidweiler, Karl B.
Jarvis, Michael J. Y.
Huestis, Marilyn A.
TI Nontargeted SWATH acquisition for identifying 47 synthetic cannabinoid
metabolites in human urine by liquid chromatography-high-resolution
tandem mass spectrometry
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Synthetic cannabinoids; Urine; Metabolites; High-resolution mass
spectrometry; Nontargeted; SWATH; LCMSMS
ID HUMAN HEPATOCYTES; PYROLYSIS PRODUCT; SMOKING MIXTURES; LC-MS/MS;
JWH-018; MS; IDENTIFICATION; IMMUNOASSAY; TOXICOLOGY; UR-144
AB Clandestine laboratories constantly produce new synthetic cannabinoids to circumvent legislative scheduling efforts, challenging and complicating toxicological analysis. Sundstrom et al. (Anal Bioanal Chem 405(26):8463-8474, [9]) and Kronstrand et al. (Anal Bioanal Chem 406(15):3599-3609, [10]) published nontargeted liquid chromatography, high-resolution, quadrupole/time-of-flight mass spectrometric (LC-QTOF) assays with validated detection of 18 and 38 urinary synthetic cannabinoid metabolites, respectively. We developed and validated a LC-QTOF urine method for simultaneously identifying the most current 47 synthetic cannabinoid metabolites from 21 synthetic cannabinoid families (5-fluoro AB-PINACA, 5-fluoro-AKB48, 5-fluoro PB-22, AB-PINACA, ADB-PINACA, AKB48, AM2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, JWH-398, MAM2201, PB-22, RCS-4, UR-144, and XLR11). beta-Glucuronidase-hydrolyzed urine was extracted with 1-mL Biotage SLE+ columns. Specimens were reconstituted in 150-mu L mobile phase consisting of 80 % A (0.1 % formic acid in water) and 20 % B (0.1 % formic acid in acetonitrile). Fifty microliters was injected, and SWATH (TM) MS data were acquired in positive electrospray mode. The LC-QTOF instrument consisted of a Shimadzu UFLCxr system and an ABSciex 5600+ TripleTOFA (R) mass spectrometer. Gradient chromatographic separation was achieved with a Restek Ultra Biphenyl column with a 0.5-mL/min flow rate and an overall run time of 15 min. Identification criteria included molecular ion mass error, isotopic profiles, retention time, and library fit criteria. Limits of detection were 0.25-5 mu g/L (N = 10 unique fortified urine samples), except for two PB-22 metabolites with limits of 10 and 20 mu g/L. Extraction efficiencies and matrix effects (N = 10) were 55-104 and -65-107 %, respectively. We present a highly useful novel LC-QTOF method for simultaneously confirming 47 synthetic cannabinoid metabolites in human urine.
C1 [Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Jarvis, Michael J. Y.] AB Sciex, Concord, ON L4K 4V8, Canada.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health
FX The authors would like to recognize Xiang He and David Cox's advice
during method development along with Kevin L. Klette and Thomas M.
Martin for providing the anonymized authentic urine specimens from the
Department of Defense drug testing program. This research was supported
by the Intramural Research Program of the National Institute on Drug
Abuse, National Institutes of Health.
NR 41
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Z9 26
U1 12
U2 67
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JAN
PY 2015
VL 407
IS 3
BP 883
EP 897
DI 10.1007/s00216-014-8118-8
PG 15
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AZ7ZY
UT WOS:000348435600025
PM 25224637
ER
PT J
AU Liu, C
Miao, LY
Sun, WB
Wu, XN
Yan, FH
Sun, HC
Zheng, CY
AF Liu, Chao
Miao, Leiying
Sun, Weibin
Wu, Xiaonan
Yan, Fuhua
Sun, Hongchen
Zheng, Changyu
TI Assessment of Transfection of AdCMV-EGFP to Rat Submandibular Gland
Cells
SO CELL BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Gene transfection; Cell culture; Adenoviral vector
ID GREEN FLUORESCENT PROTEIN; GENE-THERAPY; SALIVARY-GLANDS; DELIVERY;
VECTORS; STRATEGIES; EXPRESSION; SYSTEMS; TISSUE
AB We evaluated the efficiency of transfecting adenoviral vectors encoding enhanced green fluorescent protein (AdCMV-EGFP) into rat submandibular gland cells and the effects of gene transfer on cell proliferation and secretory function. Isolated submandibular gland cells were transfected with different titers (or multiplicity of infection, MOI) of AdCMV-EGFP. The transfection efficiency was evaluated by quantifying EGFP-positive cells by inverted fluorescence microscopy, cell proliferation by MTT assay, and cell secretory activity by measuring alpha-amylase in culture medium. A transfection efficiency of up to 70.8 % was achieved in submandibular gland cells. MTT assay showed that increased viral titers resulted in significant inhibition of cell proliferation, which occurs on day 5 post-transfection. Simultaneously, the amylase levels started to reduce with a significant decrease on day 7 after transfection. The results show that AdCMV-EGFP transfection of submandibular gland cells at higher MOI results in cytotoxicity, decreased cell proliferation, and secretory function. However, the lower adenoviral titers (e.g., 200 particles/cell) could be an efficient and safe labeling tool for gene transfer to submandibular gland cells.
C1 [Liu, Chao; Miao, Leiying; Sun, Weibin; Wu, Xiaonan; Yan, Fuhua] Nanjing Univ, Inst & Hosp Stomatol, Dept Cariol & Endodont, Sch Med, Nanjing 210008, Peoples R China.
[Sun, Hongchen] Jilin Univ, Sch Stomatol, Changchun 130021, Peoples R China.
[Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD USA.
RP Miao, LY (reprint author), Nanjing Univ, Inst & Hosp Stomatol, Dept Cariol & Endodont, Sch Med, Nanjing 210008, Peoples R China.
EM mly0720@163.com; drhcsun@163.com
FU National Natural Science Foundation [81271155, 30830108, 81300852];
Jiangsu Province Natural Science Foundation of China [BK20130079];
Science and Technology Bureau of Jiangsu Province [BL2013002]; Youth
Start Fund of Nanjing City [2011-19-198*]; Third Level Fund for the
Young Talents in the Health Field of Nanjing City
FX This work was supported by Grants from the National Natural Science
Foundation (No: 81271155, 30830108, 81300852), Jiangsu Province Natural
Science Foundation of China (BK20130079), Key Project of Science and
Technology Bureau of Jiangsu Province(No. BL2013002), the Youth Start
Fund of Nanjing City, (No. 2011-19-198*), and The Third Level Fund for
the Young Talents in the Health Field of Nanjing City.
NR 26
TC 0
Z9 0
U1 2
U2 6
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1085-9195
EI 1559-0283
J9 CELL BIOCHEM BIOPHYS
JI Cell Biochem. Biophys.
PD JAN
PY 2015
VL 71
IS 1
BP 147
EP 153
DI 10.1007/s12013-014-0177-0
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA AZ4XG
UT WOS:000348223500021
PM 25108736
ER
PT J
AU Demner-Fushman, D
Antani, S
Kalpathy-Cramer, J
Muller, H
AF Demner-Fushman, Dina
Antani, Sameer
Kalpathy-Cramer, Jayashree
Mueller, Henning
TI A decade of community-wide efforts in advancing medical image
understanding and retrieval
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Editorial Material
C1 [Demner-Fushman, Dina; Antani, Sameer] Natl Lib Med, NIH, Bethesda, MD USA.
[Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA.
[Mueller, Henning] Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland.
RP Muller, H (reprint author), Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland.
EM henning.mueller@hevs.ch
OI Muller, Henning/0000-0001-6800-9878; Kalpathy-Cramer,
Jayashree/0000-0001-8906-9618
NR 11
TC 0
Z9 0
U1 4
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
EI 1879-0771
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD JAN
PY 2015
VL 39
SI SI
BP 1
EP 2
DI 10.1016/j.compmedimag.2014.12.002
PG 2
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA AZ6NZ
UT WOS:000348337500001
PM 25572585
ER
PT J
AU Simpson, MS
You, D
Rahman, MM
Xue, ZY
Demner-Fushman, D
Antani, S
Thoma, G
AF Simpson, Matthew S.
You, Daekeun
Rahman, Md Mahmudur
Xue, Zhiyun
Demner-Fushman, Dina
Antani, Sameer
Thoma, George
TI Literature-based biomedical image classification and retrieval
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Article
DE Image-based retrieval; Case-based retrieval; Modality classification;
Compound figure separation
ID TEXT; OPTIMIZATION
AB Literature-based image informatics techniques are essential for managing the rapidly increasing volume of information in the biomedical domain. Compound figure separation, modality classification, and image retrieval are three related tasks useful for enabling efficient access to the most relevant images contained in the literature. In this article, we describe approaches to these tasks and the evaluation of our methods as part of the 2013 medical track of ImageCLEF. In performing each of these tasks, the textual and visual features used to represent images are an important consideration often left unaddressed. Therefore, we also describe a gradient-based optimization strategy for determining meaningful combinations of features and apply the method to the image retrieval task. An evaluation of our optimization strategy indicates the method is capable of producing statistically significant improvements in retrieval performance. Furthermore, the results of the 2013 ImageCLEF evaluation demonstrate the effectiveness of our techniques. In particular, our text-based and mixed image retrieval methods ranked first among all the participating groups. Published by Elsevier Ltd.
C1 [Simpson, Matthew S.; You, Daekeun; Rahman, Md Mahmudur; Xue, Zhiyun; Demner-Fushman, Dina; Antani, Sameer; Thoma, George] US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20894 USA.
RP Demner-Fushman, D (reprint author), US Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, Bethesda, MD 20894 USA.
EM ddemner@mail.nih.gov
OI Antani, Sameer/0000-0002-0040-1387
FU intramural research program of the U.S. National Library of Medicine;
National Institutes of Health
FX This work is supported by the intramural research program of the U.S.
National Library of Medicine, National Institutes of Health, and by
appointments to the U.S. National Library of Medicine Research
Participation Program administered by the Oak Ridge Institute for
Science and Education.
NR 32
TC 4
Z9 4
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
EI 1879-0771
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD JAN
PY 2015
VL 39
SI SI
BP 3
EP 13
DI 10.1016/j.compmedimag.2014.06.006
PG 11
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA AZ6NZ
UT WOS:000348337500002
PM 25016956
ER
PT J
AU Kalpathy-Cramer, J
de Herrera, AGS
Demner-Fushman, D
Antani, S
Bedrick, S
Muller, H
AF Kalpathy-Cramer, Jayashree
de Herrera, Alba Garcia Seco
Demner-Fushman, Dina
Antani, Sameer
Bedrick, Steven
Mueller, Henning
TI Evaluating performance of biomedical image retrieval systems An overview
of the medical image retrieval task at ImageCLEF 2004-2013
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Article
DE Multimodal medical retrieval; Image retrieval; Biomedical literature;
Content-based retrieval; Text-based image retrieval
ID INFORMATION; FUSION; TRACK; TEXT
AB Medical image retrieval and classification have been extremely active research topics over the past 15 years. Within the ImageCLEF benchmark in medical image retrieval and classification, a standard test bed was created that allows researchers to compare their approaches and ideas on increasingly large and varied data sets including generated ground truth. This article describes the lessons learned in ten evaluation campaigns. A detailed analysis of the data also highlights the value of the resources created. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, Boston, MA USA.
[de Herrera, Alba Garcia Seco; Mueller, Henning] Univ Appl Sci Western Switzerland HES SO, Sierre, Switzerland.
[Demner-Fushman, Dina; Antani, Sameer] Natl Lib Med, NIH, Bethesda, MD USA.
[Bedrick, Steven] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Kalpathy-Cramer, J (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
EM kalpathy@nmr.mgh.harvard.edu
OI Bedrick, Steven/0000-0002-0163-9397; Muller,
Henning/0000-0001-6800-9878; Kalpathy-Cramer,
Jayashree/0000-0001-8906-9618; Antani, Sameer/0000-0002-0040-1387
FU NIH [U01CA154602, R00LM009889]
FX JKC is funded in part by the NIH grants U01CA154602 and R00LM009889.
NR 46
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U1 2
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
EI 1879-0771
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD JAN
PY 2015
VL 39
SI SI
BP 55
EP 61
DI 10.1016/j.compmedimag.2014.03.004
PG 7
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA AZ6NZ
UT WOS:000348337500007
PM 24746250
ER
PT J
AU King, HE
Wetzell, B
Rice, KC
Riley, AL
AF King, Heather E.
Wetzell, Bradley
Rice, Kenner C.
Riley, Anthony L.
TI An assessment of MDPV-induced place preference in adult Sprague-Dawley
rats
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE MDPV; Place preference; Reward
ID CONDITIONED TASTE-AVERSION; BATH SALTS; SYNTHETIC CATHINONES; MEASURING
REWARD; ADDICTIVE DRUGS; APPARATUS BIAS; MOUSE STRAINS; COCAINE;
AMPHETAMINE; PARADIGM
AB Objective: Most drugs of abuse have both aversive and rewarding effects, and the use and abuse potential of such drugs is thought to be a function of a balance of these affective properties. Characterizing these effects and their relative balance may provide insight into abuse vulnerability. One drug that has received recent attention is methylenedioxypyrovalerone (MDPV), a monoamme transport inhibitor similar to, but significantly more potent than, cocaine. MDPV is self-administered and has been shown to produce aversive and rewarding effects in adult rats. The present study extended this characterization of the affective properties of MDPV by examining its ability to support place conditioning at a range of doses known to produce taste avoidance.
Methods: Male Sprague-Dawley rats were injected with MDPV (1, 1.8 or 3.2 mg/kg) or saline and placed on the non-preferred side of a place conditioning apparatus for 30 min. On the next day, they were given an injection of saline and placed on the preferred side. This was repeated three times for a total of four conditioning cycles, and side preference was assessed on a final test.
Results: All doses of MDPV produced significant increases in time spent in the drug-paired chamber, an effect not seen in vehicle-treated animals.
Conclusions: That the same doses of MDPV induced both taste avoidance and place preference allows assessments of how other factors might impact these effects and how they may, in turn, contribute to its abuse liability. (C) 2014 Published by Elsevier Ireland Ltd.
C1 [King, Heather E.; Wetzell, Bradley; Riley, Anthony L.] Amer Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
[Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Bethesda, MD 20892 USA.
RP King, HE (reprint author), Amer Univ, Dept Psychol, 4400 Massachusetts Ave,NW, Washington, DC 20016 USA.
EM hk9905a@american.edu
RI Wetzell, B Bradley/J-6802-2013
OI Wetzell, B Bradley/0000-0002-2723-5542
FU Mellon Foundation
FX This research was supported by a grant from the Mellon Foundation to
ALR. The Mellon Foundation had no further role in the study design, data
collection, analysis and interpretation, the writing of the report, or
the decision to submit the manuscript for publication.
NR 49
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U1 0
U2 3
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 JAN 1
PY 2015
VL 146
BP 116
EP 119
DI 10.1016/j.drugalcdep.2014.11.002
PG 4
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA AZ5LD
UT WOS:000348261600018
PM 25468817
ER
PT J
AU Dzutsev, A
Goldszmid, RS
Viaud, S
Zitvogel, L
Trinchieri, G
AF Dzutsev, Amiran
Goldszmid, Romina S.
Viaud, Sophie
Zitvogel, Laurence
Trinchieri, Giorgio
TI The role of the microbiota in inflammation, carcinogenesis, and cancer
therapy
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Review
DE Cancer; Cancer Therapy; Cancerogenesis; Inflammation; Microbiota
ID SEGMENTED FILAMENTOUS BACTERIA; HEPATITIS-B-VIRUS; MERKEL CELL
POLYOMAVIRUS; GUT MICROBIOTA; INTESTINAL MICROBIOTA; IMMUNE-SYSTEM;
HUMAN-PAPILLOMAVIRUS; HELICOBACTER-PYLORI; DENDRITIC CELLS; MYELOID
CELLS
AB Commensal microorganisms colonize barrier surfaces of all multicellular organisms, including those of humans. For more than 500 million years, commensal microorganisms and their hosts have coevolved and adapted to each other. As a result, the commensal microbiota affects many immune and nonimmune functions of their hosts, and de facto the two together comprise one metaorganism. The commensal microbiota communicates with the host via biologically active molecules. Recently, it has been reported that microbial imbalance may play a critical role in the development of multiple diseases, such as cancer, autoimmune conditions, and increased susceptibility to infection. In this review, we focus on the role of the commensal microbiota in the development, progression, and immune evasion of cancer, as well as some modulatory effects on the treatment of cancer. In particular, we discuss the mechanisms of microbiota-mediated regulation of innate and adaptive immune responses to tumors, and the consequences on cancer progression and whether tumors subsequently become resistant or susceptible to different anticancer therapeutic regiments.
C1 [Dzutsev, Amiran; Goldszmid, Romina S.; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Dzutsev, Amiran] Leidos Biomed Res Inc, Frederick, MD USA.
[Viaud, Sophie; Zitvogel, Laurence] Inst Gustave Roussy, INSERM, U1015, F-94805 Villejuif, France.
[Viaud, Sophie; Zitvogel, Laurence] Univ Paris 11, Le Kremlin Bicetre, France.
RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bldg 560 Room 31-93, Frederick, MD 21702 USA.
EM trinchig@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, National
Institute of Allergy and Infectious Diseases; Frederick National
Laboratory for Cancer Research, National Institutes of Health
[HHSN26120080001E]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, National
Institute of Allergy and Infectious Diseases, and federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under Contract HHSN26120080001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 185
TC 16
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U1 6
U2 37
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JAN
PY 2015
VL 45
IS 1
BP 17
EP 31
DI 10.1002/eji.201444972
PG 15
WC Immunology
SC Immunology
GA AZ0SO
UT WOS:000347955100004
PM 25328099
ER
PT J
AU Tripathi, BK
Lowy, DR
Zelenka, PS
AF Tripathi, Brajendra K.
Lowy, Douglas R.
Zelenka, Peggy S.
TI The Cdk5 activator P39 specifically links muskelin to myosin II and
regulates stress fiber formation and actin organization in lens
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Cdk5; p39; Muskelin; Myosin; Stress fibers; Cytoskeleton; Cell
migration; Lens
ID ESSENTIAL LIGHT-CHAIN; CELL-MIGRATION; DEPENDENT KINASE;
PHOSPHORYLATION; FILAMENT; DIFFERENTIATION; MECHANISMS; EXPRESSION;
ADHESION; MEDIATOR
AB Cyclin dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, requires p39 for its enzymatic activity, and is implicated in cytoskeletal organization and contraction in numerous cell types. The C-terminus of p39 binds muskelin, a multi-domain scaffolding protein known to affect cytoskeletal organization, but the mechanisms by which muskelin affects cytoskeletal organization remain unclear. The present study sought to determine whether p39 might serve as an adaptor protein that links muskelin to stress fibers and to investigate the possible biological relevance of such an interaction. Double immunoprecipitation showed that muskelin, p39, and myosin II are components of a single intracellular complex, and suppressing p39 abrogated the interaction between muskelin and the myosin subunits, demonstrating that p39 is required to link muskelin to myosin II. Muskelin is colocalized with myosin regulatory light chain (MRLC) and on stress fibers. The suppression of muskelin reduced Rho-GTP, MRLC phosphorylation, disrupted stress fiber organization, and promoted cell migration, all of which closely mimic the effect of Cdk5 inhibition. Moreover, suppressing muskelin and inhibiting Cdk5 together have no additional effect, indicating that muskelin plays an important role in Cdk5-dependent signaling. p39 is necessary and sufficient for Cdk5-dependent regulation of MRLC phosphorylation, as suppression of p39, but not p35, reduces MRLC phosphorylation. Together, these results demonstrate that p39 specifically links muskelin to myosin II and consequently, to stress fibers and reveal a novel role for muskelin in regulating myosin phosphorylation and cytoskeletal organization. Published by Elsevier Inc.
C1 [Tripathi, Brajendra K.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Tripathi, Brajendra K.; Zelenka, Peggy S.] NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Tripathi, BK (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Room 4112, Bethesda, MD 20892 USA.
EM tripathib@mail.nih.gov
FU National Institutes of Health, USA, Intramural Research Program
[Z01-EY000238-20]
FX We thank Dr. John Reddan, Oakland University, for providing the human
lens epithelial cells (FHL124), the NIH Imaging Core Facility for
confocal microscopy, and the FACS Core facility for isolating the
GFP-positive transfected cells. This work is supported by the National
Institutes of Health, USA, Intramural Research Program Z01-EY000238-20.
NR 39
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U1 0
U2 0
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD JAN 1
PY 2015
VL 330
IS 1
BP 186
EP 198
DI 10.1016/j.yexcr.2014.08.003
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA AZ7PX
UT WOS:000348411500016
PM 25128817
ER
PT J
AU Nemeth, K
Mezey, E
AF Nemeth, Krisztian
Mezey, Eva
TI Bone marrow stromal cells as immunomodulators. A primer for
dermatologists
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Review
DE Bone marrow stromal cells; Mesenchymal stem cells; Immunomodulation;
Inflammatory; Skin conditions
ID MESENCHYMAL STEM-CELLS; VERSUS-HOST-DISEASE;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;
PROGRESSIVE MULTIPLE-SCLEROSIS; HEMATOPOIETIC STEM; PEDIATRIC-PATIENTS;
IN-VITRO; INDOLEAMINE 2,3-DIOXYGENASE; HEMATOLOGIC MALIGNANCY
AB Bone marrow stromal cells (BMSCs, also known as mesenchymal stem cells or MSCs) represent a unique cell population in the bone marrow with a long-known function to support hematopoiesis and replace skeletal tissues. The recent discovery that BMSCs also possess potent immunoregulatory features attracted a great deal of attention from stem cell biologists, immunologists and clinicians of different specialties worldwide. Initial clinical experience along with several animal models suggested that intravenously delivered BMSCs are able to regulate a wide variety of host immune cells and act in a way that is beneficial for the recipient in a variety of diseases. The role of the present review is to give a short introduction to the biology of BMSCs and to summarize our current understanding of how BMSCs modulate the immune system with special emphasis on available clinical data. Considering the audience of this journal we will also attempt to guide dermatologists in choosing the right skin conditions where BMSCs might be considered as a therapeutic alternative. Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.
C1 [Nemeth, Krisztian; Mezey, Eva] NIDCR, Adult Stem Cell Sect, CSDB, NIH, Bethesda, MD USA.
RP Nemeth, K (reprint author), NIDCR, Adult Stem Cell Sect, CSDB, NIH, Bethesda, MD USA.
EM nemethk@mail.nih.gov
FU NIH, NIDCR Intramural Research Program
FX This work was supported by the NIH, NIDCR Intramural Research Program.
We would like to thank Dr. Sarolta Karpati for her expert opinion
regarding possible uses of MSCs in dermatology.
NR 112
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U1 2
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0923-1811
EI 1873-569X
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD JAN
PY 2015
VL 77
IS 1
BP 11
EP 20
DI 10.1016/j.jdermsci.2014.10.004
PG 10
WC Dermatology
SC Dermatology
GA CA0PO
UT WOS:000348619500002
PM 25476233
ER
PT J
AU Kondo, T
Namiki, T
Coelho, SG
Valencia, JC
Hearing, VJ
AF Kondo, Taisuke
Namiki, Takeshi
Coelho, Sergio G.
Valencia, Julio C.
Hearing, Vincent J.
TI Oculocutaneous albinism: Developing novel antibodies targeting the
proteins associated with OCA2 and OCA4
SO JOURNAL OF DERMATOLOGICAL SCIENCE
LA English
DT Article
DE OCA2; OCA4; P protein; MATP protein; BLOC-1; Albinism
ID LYSOSOME-RELATED ORGANELLES; MELANOSOMAL PROTEINS; SKIN PIGMENTATION;
EYE COLOR; GENE; MELANOCYTES; TRAFFICKING; MUTATION; BLOC-2; AP-3
AB Background: Patients with oculocutaneous albinism (OCA) have severely decreased pigmentation of their skin, hair and eyes. OCA2 and OCA4 result from mutations of the OCA2 and SLC45A2 genes, respectively, both of which disrupt the trafficking of the critical melanogenic enzyme tyrosinase to melanosomes. Both proteins encoded by those loci (termed P and MATP, respectively) have 12 putative transmembrane regions and are thought to function as transporters, although their functions and subcellular localizations remain to be characterized.
Objective: To generate specific antibodies against unique synthetic peptides encoded by P and MATP that could be used to characterize their functions and subcellular localizations. Methods: Western blotting and immunohistochemistry were used to assess the specificity of antibodies and to colocalize P and MATP proteins with various subcellular markers.
Results: Specific antibodies to the P and MATP proteins were generated that work well for Western blotting and immunohistochemistry. The localizations of P and MATP with various subcellular organelles were characterized using confocal microscopy, which revealed that they colocalize to some extent with LAMP2, but do not significantly colocalize with markers of the ER, Golgi or melanosomes. Interestingly, both P and MATP colocalize significantly with BLOC-1, a sorting component involved in the intracellular trafficking of melanosomal/lysosomal constituents.
Conclusion: These results provide a basis to understand how disrupted functions of P or MATP result in the misrouting of tyrosinase and cause the hypopigmentation seen in OCA2 and OCA4. (C) 2014 Published by Elsevier Ireland Ltd on behalf of Japanese Society for Investigative Dermatology.
C1 [Kondo, Taisuke; Namiki, Takeshi; Coelho, Sergio G.; Valencia, Julio C.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132,MSC 4256, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute at the National Institutes of Health. The
authors wish to thank Joe Mindell and Pascal Courville of NINDS and
David Adams of NHGRI for advice and useful discussions about this study.
NR 42
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0923-1811
EI 1873-569X
J9 J DERMATOL SCI
JI J. Dermatol. Sci.
PD JAN
PY 2015
VL 77
IS 1
BP 21
EP 27
DI 10.1016/j.jdermsci.2014.11.006
PG 7
WC Dermatology
SC Dermatology
GA CA0PO
UT WOS:000348619500003
PM 25530116
ER
PT J
AU Murphy, E
AF Murphy, Elizabeth
TI Solving mitochondrial mysteries
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Editorial Material
ID PERMEABILITY TRANSITION PORE; ATP SYNTHASE; PROTEIN-DEGRADATION; CALCIUM
UNIPORTER; INNER MEMBRANE; C-SUBUNIT
C1 NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Murphy, E (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU Intramural NIH HHS; NHLBI NIH HHS [ZIA HL002066]
NR 30
TC 1
Z9 1
U1 0
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD JAN
PY 2015
VL 78
BP 1
EP 2
DI 10.1016/j.yjmcc.2014.11.016
PG 2
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA AZ8SH
UT WOS:000348484400001
PM 25463271
ER
PT J
AU Harrington, JL
Murphy, E
AF Harrington, Josephine L.
Murphy, Elizabeth
TI The mitochondrial calcium uniporter: Mice can live and die without it
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Review
DE Mitochondria; Calcium; Necrosis; Ischemia-reperfusion; Mitochondrial
permeability pore
ID RAT-HEART MITOCHONDRIA; CA2+ UNIPORTER; RUTHENIUM RED;
OXIDATIVE-PHOSPHORYLATION; PERMEABILITY TRANSITION;
ENDOPLASMIC-RETICULUM; ESSENTIAL COMPONENT; CYCLOSPORINE-A; CELL-DEATH;
MCU
AB Calcium is of critical importance to mitochondrial and cell function, and calcium signaling is highly localized in the cell. When stimulated, mitochondria are capable of rapidly taking up calcium, affecting both matrix energetics within mitochondria and shaping the amplitude and frequency of cytosolic calcium "waves". During pathological conditions a large increase in mitochondrial calcium levels is thought to activate the mitochondrial permeability transition pore, resulting in cell death. The protein responsible for mitochondrial calcium uptake, the mitochondrial calcium uniporter (MCU), was identified in 2011 and its molecular elucidation has stimulated and invigorated research in this area. MCU knockout mice have been created, a variety of other regulators have been identified, and a disease phenotype in humans has been attributed to the loss of a uniporter regulator. In the three years since its molecular elucidation, further research into the MCU has revealed a complex uniporter, and raised many questions about its physiologic and pathologic cell roles. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". Published by Elsevier Ltd.
C1 [Harrington, Josephine L.; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD USA.
RP Murphy, E (reprint author), NHLBI, NIH, Mail Stop 1770, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU NHLBI [ZIA HL002066]; National Institutes of Health (NIH) Medical
Research Scholars Program [ZIA HL002065]; NIH
FX EM was supported by the NHLBI Intramural Research Program (ZIA
HL002066). Support for JH was made possible through the National
Institutes of Health (NIH) Medical Research Scholars Program (ZIA
HL002065), a public-private partnership supported jointly by the NIH and
generous contributions to the Foundation for the NIH from Pfizer Inc.,
The Doris Duke Charitable Foundation, The Newport Foundation, The
American Association for Dental Research, The Howard Hughes Medical
Institute, and the Colgate-Palmolive Company, as well as other private
donors. For a complete list, please visit the Foundation website at:
http://fnih.org/work/education-training-0/medical-researchscholars-progr
am.
NR 72
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U1 1
U2 12
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD JAN
PY 2015
VL 78
BP 46
EP 53
DI 10.1016/j.yjmcc.2014.10.013
PG 8
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA AZ8SH
UT WOS:000348484400006
PM 25451167
ER
PT J
AU Chan, XCY
Black, CM
Lin, AJ
Ping, PP
Lau, E
AF Chan, X'avia C. Y.
Black, Caitlin M.
Lin, Amanda J.
Ping, Peipei
Lau, Edward
TI Mitochondrial protein turnover: Methods to measure turnover rates on a
large scale
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Review
DE Mitochondria; Protein turnover; Proteome dynamics; Proteomics; Heavy
water
ID ISOTOPOMER DISTRIBUTION ANALYSIS; HEART-FAILURE; IN-VIVO; CARDIAC
MITOCHONDRIA; CALORIC RESTRICTION; MASS-SPECTROMETRY; MAMMALIAN-CELLS;
ANIMAL-CELLS; AMINO-ACIDS; DYNAMICS
AB Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Chan, X'avia C. Y.; Black, Caitlin M.; Lin, Amanda J.; Ping, Peipei; Lau, Edward] Univ Calif Los Angeles, NHLBI, Prote Ctr, Los Angeles, CA 90095 USA.
[Chan, X'avia C. Y.; Black, Caitlin M.; Lin, Amanda J.; Ping, Peipei; Lau, Edward] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
[Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Bioinformat, Los Angeles, CA 90095 USA.
RP Ping, PP (reprint author), Univ Calif Los Angeles, 675 Charles E Young Dr S1-619, Los Angeles, CA 90095 USA.
EM pping@mednet.ucla.edu; edwardlau@ucla.edu
OI Ping, Peipei/0000-0003-3583-3881; Lau, Edward/0000-0001-9083-5922
FU National Institutes of Health [HL-R37-63901, HHSN268201000035C]; T.C.
Laubisch endowment at UCLA; American Heart Association [12PRE11610024]
FX This work was supported by the National Institutes of Health awards
HL-R37-63901 and HHSN268201000035C, the T.C. Laubisch endowment at UCLA
to Peipei Ping; and the American Heart Association fellowships
12PRE11610024 to Edward Lau.
NR 72
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U1 2
U2 16
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD JAN
PY 2015
VL 78
BP 54
EP 61
DI 10.1016/j.yjmcc.2014.10.012
PG 8
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA AZ8SH
UT WOS:000348484400007
PM 25451168
ER
PT J
AU Perry, MR
Benson, EM
Kohne, JW
Plahovinsak, JL
Babin, MC
Platoff, GE
Yeung, DT
AF Perry, Mark R.
Benson, Eric M.
Kohne, Jonathon W.
Plahovinsak, Jennifer L.
Babin, Michael C.
Platoff, Gennady E., Jr.
Yeung, David T.
TI A novel sulfur mustard (HD) vapor inhalation exposure system for
accurate inhaled dose delivery
SO JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
LA English
DT Article
DE Dosimetry; Inhalation exposure; Inhaled dose; Methods; Sulfur mustard
vapor
AB Introduction: A custom designed HD exposure system was used to deliver controlled inhaled doses to an animal model through an endotracheal tube. Methods: Target HD vapor challenges were generated by a temperature controlled bubbler/aerosol trap, while concentration was monitored near real-time by gas chromatography. Animal breathing parameters were monitored real-time by an in-line pneumotach, pressure transducer, and Buxco pulmonary analysis computer/software. For each exposure, the challenge atmosphere was allowed to stabilize at the desired concentration while the anesthetized animal was provided humidity controlled clean air. Once the target concentration was achieved and stable, a portion of the challenge atmosphere was drawn past the endotracheal tube, where the animal inhaled the exposure ad libitum. During the exposure, HD vapor concentration and animal weight were used to calculate the needed inhaled volume to achieve the target inhaled dose (mu g/kg). The exposures were halted when the inhaled volume was achieved. Results: The exposure system successfully controlled HD concentrations from 22.2 to 278 mg/m(3) and accurately delivered inhaled doses between 49.3 and 1120 mu g/kg with actual administered doses being within 4% of the target level. Discussion: This exposure system administers specific HD inhaled doses to evaluate physiological effects and for evaluation of potential medical countermeasure treatments. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Perry, Mark R.; Benson, Eric M.; Kohne, Jonathon W.; Plahovinsak, Jennifer L.; Babin, Michael C.] Battelle Biomed Res Ctr, Columbus, OH 43201 USA.
[Platoff, Gennady E., Jr.] NIAID, NIH, Bethesda, MD 20892 USA.
[Yeung, David T.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Perry, MR (reprint author), Battelle Biomed Res Ctr, 505 King Ave, Columbus, OH 43201 USA.
EM perrym@battelle.org
OI /0000-0001-5692-0170
FU National Institutes of Health (NIH) [Y1-OD-0387-01]; National Institute
of Allergy and Infectious Diseases (NIAID); Department of Defense (DoD);
NIH; NIAID; National Institute of Neurological Disorders and Stroke
(NINDS); DoD Defense Technical Information Center (DTIC) under the
Chemical, Biological, Radiological & Nuclear Defense Information
Analysis Center (CBRNIAC) program [SP0700-00-D-3180, 0687,
832/CB-IO-OOI2]
FX This work was supported by the National Institutes of Health (NIH)
Office of the Director through an interagency agreement (OD#:
Y1-OD-0387-01) between the National Institute of Allergy and Infectious
Diseases (NIAID) and Department of Defense (DoD) and prepared under the
auspices of the NIH, NIAID, National Institute of Neurological Disorders
and Stroke (NINDS), and DoD Defense Technical Information Center (DTIC)
under the Chemical, Biological, Radiological & Nuclear Defense
Information Analysis Center (CBRNIAC) program, contract no.
SP0700-00-D-3180, delivery order number 0687, CBRNIAC Task
832/CB-IO-OOI2.
NR 21
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U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1056-8719
EI 1873-488X
J9 J PHARMACOL TOX MET
JI J. Pharmacol. Toxicol. Methods
PD JAN-FEB
PY 2015
VL 71
BP 120
EP 128
DI 10.1016/j.vascn.2014.09.009
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA AZ8FX
UT WOS:000348451500017
PM 25291290
ER
PT J
AU Noursi, S
Begg, L
Lee, N
Clayton, JA
AF Noursi, Samia
Begg, Lisa
Lee, Nancy
Clayton, Janine Austin
TI Intimate Partner Violence, Consequences on Women's Health, and Promising
Interventions Introduction
SO JOURNAL OF WOMENS HEALTH
LA English
DT Editorial Material
C1 [Noursi, Samia] NIDA, Women & Sex Gender Differences Res Program, NIH, Bethesda, MD 20892 USA.
[Begg, Lisa] NIH, Off Res Womens Hlth, Off NIH Director DPCPSI, Bethesda, MD 20892 USA.
[Lee, Nancy] US Dept HHS, Off Secretary, Washington, DC 20201 USA.
[Clayton, Janine Austin] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
[Clayton, Janine Austin] NIH, Bethesda, MD 20892 USA.
RP Noursi, S (reprint author), NIDA, NIH, Bethesda, MD 20892 USA.
EM snoursi@mail.nih.gov
NR 4
TC 0
Z9 0
U1 3
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD JAN 1
PY 2015
VL 24
IS 1
BP 49
EP 50
DI 10.1089/jwh.2014.1516
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AZ6JC
UT WOS:000348325100009
PM 25549341
ER
PT J
AU Weaver, TL
Gilbert, L
El-Bassel, N
Resnick, HS
Noursi, S
AF Weaver, Terri L.
Gilbert, Louisa
El-Bassel, Nabila
Resnick, Heidi S.
Noursi, Samia
TI Identifying and Intervening with Substance-Using Women Exposed to
Intimate Partner Violence: Phenomenology, Comorbidities, and Integrated
Approaches Within Primary Care and Other Agency Settings
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PERPETRATOR ALCOHOL-USE;
POSTTRAUMATIC-STRESS; DRUG-USE; EMERGENCY CARE; HIV PREVENTION; PTSD
SYMPTOMS; UNITED-STATES; USE DISORDERS; METAANALYSIS
AB Substance use and/or disorders (SUDs) have been identified as a significant correlate of intimate partner violence (IPV) exposure and present complex issues that intersect with the topography of IPV, attendant mental health, and physical co-morbidities and may pose barriers to primary care- and other agency-based screening and intervention efforts. Despite substantial research indicating significantly higher rates of all types and severity of IPV victimization among women with SUDs and bidirectional associations between partner or self-use of drugs or alcohol and IPV victimization, effective screening, brief interventions, coordinated systems of care, and treatment approaches to address these co-occurring problems remain very limited. We integrated select research examining the intersection of IPV victimization and SUDs and several comorbidities that have significant public health impact and provided recommendations for scaling up targeted interventions to redress these co-occurring problems among women in primary, emergency, and other care settings.
C1 [Weaver, Terri L.] St Louis Univ, Dept Psychol, St Louis, MO 63108 USA.
[Gilbert, Louisa; El-Bassel, Nabila] Columbia Univ, Sch Social Work, New York, NY USA.
[Resnick, Heidi S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA.
[Noursi, Samia] NIDA, NIH, Bethesda, MD 20892 USA.
RP Weaver, TL (reprint author), St Louis Univ, Dept Psychol, 3700 Lindell Blvd,Morrissey Hall,Suite 2729, St Louis, MO 63108 USA.
EM weavert@slu.edu
FU NIDA [R01DA023099]
FX Dr. Resnick's effort was partially supported by NIDA grant R01DA023099
(PI: Resnick). Views expressed herein are those of the authors and do
not necessarily reflect those of NIDA or other institutions.
NR 46
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PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD JAN 1
PY 2015
VL 24
IS 1
BP 51
EP 56
DI 10.1089/jwh.2014.4866
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AZ6JC
UT WOS:000348325100010
PM 25554915
ER
PT J
AU Ghandour, RM
Campbell, JC
Lloyd, J
AF Ghandour, Reem M.
Campbell, Jacquelyn C.
Lloyd, Jacqueline
TI Screening and Counseling for Intimate Partner Violence: A Vision for the
Future
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID PREVENTIVE SERVICES; CARE SETTINGS; SURVIVORS; WOMEN; INTERVENTION;
HEALTH; ABUSE
AB We describe a vision of screening and intervention for Intimate Partner Violence informed by deliberations during the December 2013 Intimate Partner Violence Screening and Counseling Research Symposium and the resultant manuscripts featured in this special issue of the Journal of Women's Health. Our vision includes universal screening and intervention, when indicated, which occurs routinely as part of comprehensive physical and behavioral health services that are both patient centered and trauma informed. Areas for future research needed to realize this vision are discussed.
C1 [Ghandour, Reem M.] Maternal & Child Hlth Bur, US Dept HHS, Hlth Resources & Serv Adm, Off Epidemiol & Res, Rockville, MD 20857 USA.
[Campbell, Jacquelyn C.] Johns Hopkins Univ, Sch Nursing, Dept Community Publ Hlth, Baltimore, MD USA.
[Lloyd, Jacqueline] NIDA, US Dept HHS, NIH, Div Epidemiol Serv & Prevent Res,Prevent Res Bran, Bethesda, MD 20892 USA.
RP Ghandour, RM (reprint author), Maternal & Child Hlth Bur, Div Epidemiol, Off Epidemiol & Res, Hlth Resources & Serv Adm, 5600 Fishers Lane,Room 10-77, Rockville, MD 20857 USA.
EM rghandour@hrsa.gov
NR 34
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U1 5
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD JAN 1
PY 2015
VL 24
IS 1
BP 57
EP 61
DI 10.1089/jwh.2014.4885
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AZ6JC
UT WOS:000348325100011
PM 25405270
ER
PT J
AU Hamberger, LK
Rhodes, K
Brown, J
AF Hamberger, L. Kevin
Rhodes, Karin
Brown, Jeremy
TI Screening and Intervention for Intimate Partner Violence in Healthcare
Settings: Creating Sustainable System-Level Programs
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; DOMESTIC VIOLENCE; WOMEN; EMERGENCY;
BARRIERS; VICTIMS; MODEL; IDENTIFICATION; OUTCOMES; ALCOHOL
AB Among the barriers to routine screening for intimate partner violence (IPV) are time constraints, a lack of protocols and policies, and departmental philosophies of care that may conflict with IPV screening recommendations. To address these barriers, systems-level interventions are needed; in this article, we describe one model that may overcome these obstacles. We discuss how this systemic approach may best be implemented in both out-patient clinics and emergency departments (EDs) and note that evidence for its success will be required.
C1 [Hamberger, L. Kevin] Med Coll Wisconsin, Dept Family & Community Med, Milwaukee, WI 53226 USA.
[Rhodes, Karin] Univ Penn, Dept Emergency Med, Perlman Sch Med, Philadelphia, PA 19104 USA.
[Brown, Jeremy] NIH, Off Emergency Care Res, Bethesda, MD 20892 USA.
RP Hamberger, LK (reprint author), Wheaton Franciscan All St Family Care Ctr, 2400 W Villard Ave, Milwaukee, WI 53209 USA.
EM kevinh@mcw.edu
FU HHS
FX This article is based on presentations by the authors at the
HHS-sponsored Intimate Partner Violence Screening and Counseling
Research Symposium, December 9, 2013, Rockville, MD.
NR 57
TC 1
Z9 1
U1 4
U2 15
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD JAN 1
PY 2015
VL 24
IS 1
BP 86
EP 91
DI 10.1089/jwh.2014.4861
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AZ6JC
UT WOS:000348325100014
PM 25412012
ER
PT J
AU Miller, E
McCaw, B
Humphreys, BL
Mitchell, C
AF Miller, Elizabeth
McCaw, Brigid
Humphreys, Betsy L.
Mitchell, Connie
TI Integrating Intimate Partner Violence Assessment and Intervention into
Healthcare in the United States: A Systems Approach
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; DOMESTIC VIOLENCE; PREVENTIVE SERVICES;
WOMENS EXPERIENCES; MEDICAL-CARE; PANDORA BOX; BARRIERS; ABUSE;
SETTINGS; PROGRAM
AB The Institute of Medicine, United States Preventive Services Task Force (USPSTF), and national healthcare organizations recommend screening and counseling for intimate partner violence (IPV) within the US healthcare setting. The Affordable Care Act includes screening and brief counseling for IPV as part of required free preventive services for women. Thus, IPV screening and counseling must be implemented safely and effectively throughout the healthcare delivery system. Health professional education is one strategy for increasing screening and counseling in healthcare settings, but studies on improving screening and counseling for other health conditions highlight the critical role of making changes within the healthcare delivery system to drive desired improvements in clinician screening practices and health outcomes.
This article outlines a systems approach to the implementation of IPV screening and counseling, with a focus on integrated health and advocacy service delivery to support identification and interventions, use of electronic health record (EHR) tools, and cross-sector partnerships. Practice and policy recommendations include (1) ensuring staff and clinician training in effective, client-centered IPV assessment that connects patients to support and services regardless of disclosure; (2) supporting enhancement of EHRs to prompt appropriate clinical care for IPV and facilitate capturing more detailed and standardized IPV data; and (3) integrating IPV care into quality and meaningful use measures. Research directions include studies across various health settings and populations, development of quality measures and patient-centered outcomes, and tests of multilevel approaches to improve the uptake and consistent implementation of evidence-informed IPV screening and counseling guidelines.
C1 [Miller, Elizabeth] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Adolescent & Young Adult Med, Pittsburgh, PA 15213 USA.
[McCaw, Brigid] Kaiser Permanente, Family Violence Prevent Program, Oakland, CA USA.
[Humphreys, Betsy L.] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[Mitchell, Connie] Calif Dept Publ Hlth, Ctr Family Hlth, Sacramento, CA USA.
RP Miller, E (reprint author), Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Adolescent & Young Adult Med, 3420 Fifth Ave, Pittsburgh, PA 15213 USA.
EM elizabeth.miller@chp.edu
FU National Institute of Child Health and Human Development [R01HD064407];
Intramural Program of the National Institutes of Health (NIH), National
Library of Medicine (NLM)
FX This article was supported in part by funding from the National
Institute of Child Health and Human Development (R01HD064407, Miller).
This work was supported in part by the Intramural Program of the
National Institutes of Health (NIH), National Library of Medicine (NLM).
NR 65
TC 15
Z9 15
U1 5
U2 28
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD JAN 1
PY 2015
VL 24
IS 1
BP 92
EP 99
DI 10.1089/jwh.2014.4870
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA AZ6JC
UT WOS:000348325100015
PM 25606823
ER
PT J
AU Vrancken, B
Lemey, P
Rambaut, A
Bedford, T
Longdon, B
Guenthard, HF
Suchard, MA
AF Vrancken, Bram
Lemey, Philippe
Rambaut, Andrew
Bedford, Trevor
Longdon, Ben
Guenthard, Huldrych F.
Suchard, Marc A.
TI Simultaneously estimating evolutionary history and repeated traits
phylogenetic signal: applications to viral and host phenotypic evolution
SO METHODS IN ECOLOGY AND EVOLUTION
LA English
DT Article
DE adaptation; Bayesian phylogenetics; comparative approach; virulence;
virus evolution
ID NEUTRALIZING ANTIBODIES; DRUG-RESISTANCE; HIV-1 INFECTION;
INFLUENZA-VIRUS; MODELS; DYNAMICS; ADAPTATION; TIME; EPIDEMIOLOGY;
TRANSMISSION
AB Phylogenetic signal quantifies the degree to which resemblance in continuously valued traits reflects phylogenetic relatedness. Measures of phylogenetic signal are widely used in ecological and evolutionary research and are recently gaining traction in viral evolutionary studies. Standard estimators of phylogenetic signal frequently condition on data summary statistics of the repeated trait observations and fixed phylogenetics trees, resulting in information loss and potential bias. To incorporate the observation process and phylogenetic uncertainty in a model-based approach, we develop a novel Bayesian inference method to simultaneously estimate the evolutionary history and phylogenetic signal from molecular sequence data and repeated multivariate traits. Our approach builds upon a phylogenetic diffusion framework that models continuous trait evolution as a Brownian motion process and incorporates Pagel's transformation parameter to estimate dependence among traits. We provide a computationally efficient inference implementation in the BEAST software package. We evaluate the synthetic performance of the Bayesian estimator of phylogenetic signal against standard estimators and demonstrate the use of our coherent framework to address several virus-host evolutionary questions, including virulence heritability for HIV, antigenic evolution in influenza and HIV, and Drosophila sensitivity to sigma virus infection. Finally, we discuss model extensions that will make useful contributions to our flexible framework for simultaneously studying sequence and trait evolution.
C1 [Vrancken, Bram; Lemey, Philippe] KU Leuven Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Leuven, Belgium.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bedford, Trevor] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Longdon, Ben] Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.
[Guenthard, Huldrych F.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland.
[Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath & Human Genet, Los Angeles, CA 90095 USA.
[Suchard, Marc A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA.
RP Vrancken, B (reprint author), KU Leuven Univ Leuven, Rega Inst, Dept Microbiol & Immunol, Leuven, Belgium.
EM bram.vrancken@rega.kuleuven.be
RI SHCS, int. coll. B/G-4090-2011; SHCS, all/G-4072-2011; Longdon,
Ben/F-4132-2010; Infektiologie, USZ/A-6921-2011; gunthard,
huldrych/F-1724-2011;
OI Longdon, Ben/0000-0001-6936-1697; gunthard,
huldrych/0000-0002-1142-6723; Bedford, Trevor/0000-0002-4039-5794;
Rambaut, Andrew/0000-0003-4337-3707
FU European Union [278433-PREDEMICS, 223131]; ERC [260864]; National
Institutes of Health [R01 AI107034, R01 HG006139]; National Science
Foundation [DMS 1264153, IIS 1251151]; Fonds door Wetenschappelijk
Onderzoek Vlaanderen (FWO) [1.5.252.12N]; Swiss HIV Cohort Study - Swiss
National Science Foundation (SNF) [33CS30-134277, 33CS30-148522]; SHCS
[470, 528, 569]; SHCS Research Foundation; Swiss National Science
Foundation [324730-130865]; Yvonne-Jacob Foundation; Union Bank of
Switzerland; Gilead, Switzerland; University of Zurichs Clinical
Research Priority Program (CRPP) Viral Infectious Diseases: Zurich
Primary HIV Infection Study
FX The research leading to these results has received funding from the
European Union Seventh Framework Programme [FP7/2007-2013] under Grant
Agreement No. 278433-PREDEMICS and ERC Grant Agreement No. 260864. This
work was also supported by National Institutes of Health Grants R01
AI107034 and R01 HG006139 and National Science Foundation Grants DMS
1264153 and IIS 1251151. This research was supported by the Fonds door
Wetenschappelijk Onderzoek Vlaanderen (FWO) (krediet no. 1.5.252.12N).
The SHCS is financed in the framework of the Swiss HIV Cohort Study,
supported by the Swiss National Science Foundation (SNF grant
#33CS30-134277 and #33CS30-148522). Furthermore, the SHCS drug
resistance data base was financed by the following funding sources: the
SHCS projects #470, 528, 569, the SHCS Research Foundation, the Swiss
National Science Foundation (grant #324730-130865 (to HFG), the European
Union Seventh Framework Program (Grant FP7/2007-2013), under the
Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN; Grant
223131, to HFG), the Yvonne-Jacob Foundation (to HFG), and by a further
research grant of the Union Bank of Switzerland, in the name of an
anonymous donor to HFG, an unrestricted research grant from Gilead,
Switzerland, to the SHCS Research Foundation, and by the University of
Zurichs Clinical Research Priority Program (CRPP) Viral Infectious
Diseases: Zurich Primary HIV Infection Study (to HFG). We thank Samuel
Alizon for sharing data and R scripts, Tanja Stadler for sharing python
scripts, Hanneke Schuitemaker & Zelda Euler for sharing sequence data
and Christophe Fraser & George Shirreff for sharing insights into their
preliminary work. We thank the patients participating in the SHCS and
the members of the SHCS: Aubert V, Battegay M, Bernasconi E, Boni J,
Bucher HC, Burton-Jeangros C, Calmy A, Cavassini M, Egger M, Elzi L,
Fehr J, Fellay J, Francioli P, Furrer H (Chairman of the Clinical and
Laboratory Committee), Fux CA, Gorgievski M, Gunthard H (President of
the SHCS), Haerry D (Deputy of 'Positive Council'), Hasse B, Hirsch HH,
Hirschel B, Hosli I, Kahlert C, Kaiser L, Keiser O, Kind C, Klimkait T,
Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Metzner K,
Muller N, Nadal D, Pantaleo G, Rauch A (Chairman of the Scientific
Board), Regenass S, Rickenbach M (Head of Data Center), Rudin C
(Chairman of the Mother & Child Substudy), Schmid P, Schultze D,
Schoni-Affolter F, Schupbach J, Speck R, Taffe P, Tarr P, Telenti A,
Trkola A, Vernazza P, Weber R, Yerly S.
NR 71
TC 3
Z9 3
U1 3
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2041-210X
EI 2041-2096
J9 METHODS ECOL EVOL
JI Methods Ecol. Evol.
PD JAN
PY 2015
VL 6
IS 1
BP 67
EP 82
DI 10.1111/2041-210X.12293
PG 16
WC Ecology
SC Environmental Sciences & Ecology
GA AZ9MC
UT WOS:000348537800007
PM 25780554
ER
PT J
AU Vega, MG
Zarek, SM
Bhagwat, M
Segars, JH
AF Vega, Mario G.
Zarek, Shvetha M.
Bhagwat, Medha
Segars, James H.
TI Gonadotropin Surge-inhibiting/attenuating Factors: A Review of Current
Evidence, Potential Applications, and Future Directions for Research
SO MOLECULAR REPRODUCTION AND DEVELOPMENT
LA English
DT Review
ID FOLLICLE-STIMULATING-HORMONE; ATTENUATING FACTOR GNSAF; RFAMIDE-RELATED
PEPTIDE-3; HUMAN MENOPAUSAL GONADOTROPIN; POLYCYSTIC-OVARY-SYNDROME;
HUMAN GRANULOSA-CELLS; HUMAN SERUM-ALBUMIN; LUTEINIZING-HORMONE;
SUPEROVULATED WOMEN; INHIBITING FACTOR
AB Animal studies in the 1980s suggested the existence of an ovarian hormone, termed gonadotropin surge-inhibiting/attenuating factor (GnSIF/AF), that modulates pituitary secretion of luteinizing hormone (LH). Given the importance of identifying regulatory factors of the hypothalamic-pituitary-ovarian axis and the accumulating data suggesting its existence, we conducted a comprehensive literature search using PubMed, Web of Science, Scopus, and Embase to identify articles related to GnSIF/AF. The search generated 161 publications, of which 97 were included in this study. Several attempts have been made to identify and characterize this hormone and several candidates have been identified, but the protein sequences of these putative GnSIF/AF factors differ widely from one study to another. In addition, while the RF-amide RFRP-3 is known foremost as a neuropeptide, some research supports an ovarian origin for this non-steroidal hormone, thereby suggesting a role for RFRP-3 either as a co-modulator of GnSIF/AF or as a gonadotropin-inhibiting factor in the hypothalamus (GnIH). Discovery of the KNDy neurons that modulate GnRH secretion, on the other hand, further encourages the search for substance(s) that modulate their activity and that indirectly affect LH secretion and the hypothalamic-pituitary-ovarian axis. While it has remained an elusive hormone, GnSIF/AF holds many potential applications for contraception, in vitro fertilization, and/or cancer as well as for understanding polycystic ovary syndrome, metabolic diseases, and/or pubertal development. In this review, we rigorously examine the available evidence regarding the existence of GnSIF/AF, previous attempts at its identification, limitations to its discovery, future directions of research, and potential clinical applications. Mol. Reprod. Dev. 82: 2-16, 2015. (c) 2014 Wiley Periodicals, Inc.
C1 [Vega, Mario G.] St Lukes Roosevelt Hosp, Dept Obstet & Gynecol, New York, NY 10025 USA.
[Zarek, Shvetha M.; Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Bhagwat, Medha] NIH, Bioinformat Support Program, Bethesda, MD 20892 USA.
RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 CRC Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU National Institutes of Health [ZIA-HD 008737-13]
FX Grant sponsor: National Institutes of Health; Grant number: ZIA-HD
008737-13
NR 120
TC 1
Z9 1
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1040-452X
EI 1098-2795
J9 MOL REPROD DEV
JI Mol. Reprod. Dev.
PD JAN
PY 2015
VL 82
IS 1
BP 2
EP 16
DI 10.1002/mrd.22439
PG 15
WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology;
Reproductive Biology
SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology;
Reproductive Biology
GA CA1EX
UT WOS:000348656700002
PM 25581424
ER
PT J
AU Frank, GA
Narayan, K
Bess, JW
Del Prete, GQ
Wu, XW
Moran, A
Hartnell, LM
Earl, LA
Lifson, JD
Subramaniam, S
AF Frank, Gabriel A.
Narayan, Kedar
Bess, Julian W., Jr.
Del Prete, Gregory Q.
Wu, Xiongwu
Moran, Amy
Hartnell, Lisa M.
Earl, Lesley A.
Lifson, Jeffrey D.
Subramaniam, Sriram
TI Maturation of the HIV-1 core by a non-diffusional phase transition
SO Nature Communications
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CRYOELECTRON MICROSCOPY; MATRIX PROTEIN;
ELECTRON CRYOTOMOGRAPHY; ENVELOPE INCORPORATION; GAG PROTEIN; VIRIONS;
MEMBRANE; DOMAIN; PHOSPHATIDYLINOSITOL-(4,5)-BISPHOSPHATE
AB The formation of the HIV-1 core is the final step in the viral maturation pathway, resulting in the formation of infectious virus. Most current models for HIV-1 core formation suggest that, upon proteolytic cleavage from the immature Gag, capsid (CA) dissociates into the viral interior before reforming into the core. Here we present evidence for an alternate view of core formation by taking advantage of our serendipitous observation of large membrane-enclosed structures in HIV-1 supernatants from infected cells. Cryo-electron tomographic studies show that these structures, which contain ordered arrays of what is likely the membrane-associated matrix protein, contain multiple cores that can be captured at different stages of maturation. Our studies suggest that HIV maturation involves a non-diffusional phase transition in which the detaching layer of the cleaved CA lattice is gradually converted into a roll that ultimately forms the surface of the mature conical core.
C1 [Frank, Gabriel A.; Narayan, Kedar; Hartnell, Lisa M.; Earl, Lesley A.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Bess, Julian W., Jr.; Del Prete, Gregory Q.; Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA.
[Wu, Xiongwu] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Moran, Amy] NIH, Natl Lab Med, Bethesda, MD 20892 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU NIH IATAP program; Center for Cancer Research at the National Cancer
Institute, NIH, Bethesda, MD; National Cancer Institute, the National
Institutes of Health [HHSN261200800001E]
FX This work was supported by funds from the NIH IATAP program and Center
for Cancer Research at the National Cancer Institute, NIH, Bethesda, MD
(to S.S.) and from the National Cancer Institute, the National
Institutes of Health contract #HHSN261200800001E (to J.D.L.). We thank
S. Fellini, S. Chacko and their colleagues for continued support with
use of the Biowulf cluster for computing at NIH. We thank Kunio
Nagashima for assistance with preparation of EM blocks for imaging.
NR 53
TC 22
Z9 22
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 5854
DI 10.1038/ncomms6854
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA1XF
UT WOS:000348701500002
PM 25569620
ER
PT J
AU Furusawa, T
Rochman, M
Taher, L
Dimitriadis, EK
Nagashima, K
Anderson, S
Bustin, M
AF Furusawa, Takashi
Rochman, Mark
Taher, Leila
Dimitriadis, Emilios K.
Nagashima, Kunio
Anderson, Stasia
Bustin, Michael
TI Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs
nuclear sturdiness
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DILATED CARDIOMYOPATHY; GENE-EXPRESSION; LINKER HISTONE; LAMIN;
HETEROCHROMATIN; ENVELOPE; DIFFERENTIATION; MOUSE; DNA; INTEGRITY
AB In most metazoan nuclei, heterochromatin is located at the nuclear periphery in contact with the nuclear lamina, which provides mechanical stability to the nucleus. We show that in cultured cells, chromatin decompaction by the nucleosome binding protein HMGN5 decreases the sturdiness, elasticity and rigidity of the nucleus. Mice overexpressing HMGN5, either globally or only in the heart, are normal at birth but develop hypertrophic heart with large cardiomyoctyes, deformed nuclei and disrupted lamina and die of cardiac malfunction. Chromatin decompaction is seen in cardiomyocytes of newborn mice but misshaped nuclei with disrupted lamina are seen only in adult cardiomyocytes, suggesting that loss of heterochromatin diminishes the ability of the nucleus to withstand the mechanical forces of the contracting heart. Thus, heterochromatin enhances the ability of the nuclear lamina to maintain the sturdiness and shape of the eukaryotic nucleus; a structural role for chromatin that is distinct from its genetic functions.
C1 [Furusawa, Takashi; Rochman, Mark; Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Taher, Leila] Univ Rostock, Inst Biostat & Informat Med & Ageing Res, D-18057 Rostock, Germany.
[Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, Biomed Engn & Phys Sci Shared Resource Program, NIH, Bethesda, MD 20892 USA.
[Nagashima, Kunio] SAIC Frederick Inc, Leidos Biomed Res Inc, Elect Microscopy Lab, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Anderson, Stasia] NHLBI, Anim Core Facil, NIH, Bethesda, MD 20892 USA.
RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM bustinm@mail.nih.gov
RI Bustin, Michael/G-6155-2015
FU Center for Cancer Research; National Cancer Institute
[HHSN26120080001E]; National Library of Medicine, NIH
FX The research was supported by the Center for Cancer Research, the
National Cancer Institute, in part under contract HHSN26120080001E and
by the National Library of Medicine, NIH. We thank Drs Tom Misteli and
Nard Kubben for a gift of Lmna-/- and Lmna+/+
cells, to Dr Nina Bubunenko, LMT, Frederick for help with the Affymetrix
arrays, to Susan Garfield (CCR Confocal Microscopy Core Facility,
Laboratory of Experimental Carcinogenesis, NCI, NIH) for Confocal
Microscopy, to Dr Corrinne Lobe (University of Toronto) for CAG-LacZ
vector, to Lauren Brinster (Division of Veterinary Resources, Office of
Research Services, NIH) for pathology, to Dr Chinmay Trivedi (the
University of Pennsylvania School of Medicine) for primer sequences for
alpha-MHC and beta-MHC, and to Dr Michael Schneider (Imperial College
London) for alpha-MHC-Cre mouse. We thank Dr Robert Adelstein (NHLBI,
NIH) for numerous helpful discussions and advice on cardiac function, to
Dr Gabi Gerlitz (the Ariel University, Israel) for discussions on the
non-genomic functions of chromatin and to Dr Tamar Kleinberger
(Technion, Israel) for comments on the manuscript.
NR 60
TC 7
Z9 7
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 6138
DI 10.1038/ncomms7138
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3UM
UT WOS:000348832300009
PM 25609380
ER
PT J
AU Khaled, WT
Lee, SC
Stingl, J
Chen, XF
Ali, HR
Rueda, OM
Hadi, F
Wang, JX
Yu, Y
Chin, SF
Stratton, M
Futreal, A
Jenkins, NA
Aparicio, S
Copeland, NG
Watson, CJ
Caldas, C
Liu, P
AF Khaled, Walid T.
Lee, Song Choon
Stingl, John
Chen, Xiongfeng
Ali, H. Raza
Rueda, Oscar M.
Hadi, Fazal
Wang, Juexuan
Yu, Yong
Chin, Suet-Feung
Stratton, Mike
Futreal, Andy
Jenkins, Nancy A.
Aparicio, Sam
Copeland, Neal G.
Watson, Christine J.
Caldas, Carlos
Liu, Pentao
TI BCL11A is a triple-negative breast cancer gene with critical functions
in stem and progenitor cells
SO Nature Communications
LA English
DT Article
ID MAMMARY-GLAND; LYMPHOID DEVELOPMENT; MOLECULAR PORTRAITS; SUPPRESSOR
GENE; EXPRESSION; TUMORS; MOUSE; IDENTIFICATION; DIFFERENTIATION;
OVEREXPRESSION
AB Triple-negative breast cancer (TNBC) has poor prognostic outcome compared with other types of breast cancer. The molecular and cellular mechanisms underlying TNBC pathology are not fully understood. Here, we report that the transcription factor BCL11A is overexpressed in TNBC including basal-like breast cancer (BLBC) and that its genomic locus is amplified in up to 38% of BLBC tumours. Exogenous BCL11A overexpression promotes tumour formation, whereas its knockdown in TNBC cell lines suppresses their tumourigenic potential in xenograft models. In the DMBA-induced tumour model, Bcl11a deletion substantially decreases tumour formation, even in p53-null cells and inactivation of Bcl11a in established tumours causes their regression. At the cellular level, Bcl11a deletion causes a reduction in the number of mammary epithelial stem and progenitor cells. Thus, BCL11A has an important role in TNBC and normal mammary epithelial cells. This study highlights the importance of further investigation of BCL11A in TNBC-targeted therapies.
C1 [Khaled, Walid T.; Lee, Song Choon; Wang, Juexuan; Yu, Yong; Stratton, Mike; Futreal, Andy; Liu, Pentao] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Khaled, Walid T.; Hadi, Fazal] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England.
[Stingl, John; Ali, H. Raza; Rueda, Oscar M.; Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England.
[Stingl, John; Ali, H. Raza; Rueda, Oscar M.; Chin, Suet-Feung; Caldas, Carlos] Univ Cambridge, Li Ka Shing Ctr, Dept Oncol, Cambridge CB2 0RE, England.
[Chen, Xiongfeng] NCI, SAIC Frederic, Frederick, MD 21701 USA.
[Ali, H. Raza; Caldas, Carlos] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England.
[Jenkins, Nancy A.; Copeland, Neal G.] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Aparicio, Sam] BC Canc Agcy, Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada.
[Watson, Christine J.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Caldas, Carlos] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge CB2 2QQ, England.
[Caldas, Carlos] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 2QQ, England.
RP Khaled, WT (reprint author), Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
EM wtk22@cam.ac.uk; pl2@sanger.ac.uk
OI chin, suet-feung/0000-0001-5697-1082
FU Sanger Institute; BBSRC project grant; Junior Research Fellowship,
King's College, Cambridge; Cancer Research UK Career establishment
award; Cancer Research UK; University of Cambridge; Hutchison Whampoa
Limited; BBSRC; MRC; BCC; Wellcome Trust [098051]
FX W.T.K., S.C.L. and J.W. were funded by the Sanger Institute. W.T.K. was
also funded by a BBSRC project grant and a Junior Research Fellowship,
King's College, Cambridge and a Cancer Research UK Career establishment
award. J.S. is funded by Cancer Research UK, The University of Cambridge
and Hutchison Whampoa Limited. C.J.W. is funded by BBSRC, MRC and BCC.
We would like to thank Dr Floris Foijer and Professor Allan Bradley for
providing the p53 cko mice. We thank Dr Shannon Burke, Dr Sara Pensa and
Lauma Skruzmane for comments on the manuscript. We thank Miss Malgorzata
Gawedzka from the W.T.K. lab for the technical assistance. We thank the
Sanger Institute RSF, the flow cytometry core and microarray facilities
for the technical assistance. This work is supported by Wellcome Trust
(Grant number-098051) (P.L.).
NR 60
TC 19
Z9 19
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 1038
DI 10.1038/ncomms6987
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3MY
UT WOS:000348812100005
PM 25574598
ER
PT J
AU Wang, YC
Sui, YJ
Kato, S
Hogg, AE
Steel, JC
Morris, JC
Berzofsky, JA
AF Wang, Yichuan
Sui, Yongjun
Kato, Shingo
Hogg, Alison E.
Steel, Jason C.
Morris, John C.
Berzofsky, Jay A.
TI Vaginal type-II mucosa is an inductive site for primary CD8(+) T-cell
mucosal immunity
SO Nature Communications
LA English
DT Article
ID PERIPHERAL LYMPHOID ORGANS; INTRAVAGINAL IMMUNIZATION;
ABNORMAL-DEVELOPMENT; PRIMARY ACTIVATION; LANGERHANS CELLS; DENDRITIC
CELLS; GENITAL HERPES; DEFICIENT MICE; CUTTING EDGE; NAIVE CD4(+)
AB The structured lymphoid tissues are considered the only inductive sites where primary T-cell immune responses occur. The naive T cells in structured lymphoid tissues, once being primed by antigen-bearing dendritic cells, differentiate into memory T cells and traffic back to the mucosal sites through the bloodstream. Contrary to this belief, here we show that the vaginal type-II mucosa itself, despite the lack of structured lymphoid tissues, can act as an inductive site during primary CD8(+) T-cell immune responses. We provide evidence that the vaginal mucosa supports both the local immune priming of naive CD8(+) T cells and the local expansion of antigen-specific CD8(+) T cells, thereby demonstrating a different paradigm for primary mucosal T-cell immune induction.
C1 [Wang, Yichuan; Sui, Yongjun; Kato, Shingo; Hogg, Alison E.; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hogg, Alison E.] Aeras, Rockville, MD 20850 USA.
[Steel, Jason C.] Univ Queensland, Brisbane, Qld 4120, Australia.
[Steel, Jason C.] Gallipoli Med Res Fdn, Greenslopes, Qld 4120, Australia.
[Morris, John C.] Univ Cincinnati, Inst Canc, Cincinnati, OH 45267 USA.
RP Sui, YJ (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM Suiy@mail.nih.gov; berzofsj@mail.nih.gov
RI Steel, Jason/D-1805-2013
OI Steel, Jason/0000-0003-3608-7542
FU NCI [ZO1 SC 004020]
FX This work is supported by NCI intramural funding ZO1 SC 004020. We thank
Drs Warren Strober and Brian Kelsall for the critical reading of this
manuscript, Dr Leonid Margolis' lab for valuable suggestions on vaginal
tissue culture, Dr Shunsuke Sakai and Dr Daniel L. Barber for the advice
on intravascular T-cell staining, the NIH tetramer facility for
providing tetramer reagents, Dr Laurel Lagenaur and NIAID Biological
Imaging Facility for photomicrography of the IHC stained vaginal tissue
sections.
NR 62
TC 1
Z9 1
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 6100
DI 10.1038/ncomms7100
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3TJ
UT WOS:000348828900003
PM 25600442
ER
PT J
AU Imperiale, A
Moussallieh, FM
Roche, P
Battini, S
Cicek, AE
Sebag, F
Brunaud, L
Barlier, A
Elbayed, K
Loundou, A
Bachellier, P
Goichot, B
Stratakis, CA
Pacak, K
Namer, IJ
Taieb, D
AF Imperiale, Alessio
Moussallieh, Franois-Marie
Roche, Philippe
Battini, Stephanie
Cicek, A. Ercument
Sebag, Frederic
Brunaud, Laurent
Barlier, Anne
Elbayed, Karim
Loundou, Anderson
Bachellier, Philippe
Goichot, Bernard
Stratakis, Constantine A.
Pacak, Karel
Namer, Izzie-Jacques
Taieb, david
TI Metabolome Profiling by HRMAS NMR Spectroscopy of Pheochromocytomas and
Paragangliomas Detects SDH Deficiency: Clinical and Pathophysiological
Implications
SO NEOPLASIA
LA English
DT Article
ID CARNEY TRIAD; CROSS-VALIDATION; GENE-MUTATIONS; METABONOMICS;
INFORMATION; REGRESSION; DATABASE; CANCER; CELLS; HMDB
AB Succinate dehydrogenase gene (SDHx) mutations increase susceptibility to develop pheochromocytomas/paragangliomas (PHEOs/PGLs). In the present study, we evaluate the performance and clinical applications of H-1 high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy-based global metabolomic profiling in a large series of PHEOs/PGLs of different genetic backgrounds. Eighty-seven PHEOs/PGLs (48 sporadic/23 SDHx/7 von Hippel-Lindau/5 REarranged during Transfection/3 neurofibromatosis type 1/1 hypoxia-inducible factor 2 alpha), one SDHD variant of unknown significance, and two Carney triad (CTr)-related tumors were analyzed by HRMAS-NMR spectroscopy. Compared to sporadic, SDHx-related PHEOs/PGLs exhibit a specific metabolic signature characterized by increased levels of succinate (P < .0001), methionine (P =.002), glutamine (P =.002), and myoinositol (P < .0007) and decreased levels of glutamate (P < .0007), regardless of their location and catecholamine levels. Uniquely, ATP/ascorbate/glutathione was found to be associated with the secretory phenotype of PHEOs/PGLs, regardless of their genotype (P < .0007). The use of succinate as a single screening test retained excellent accuracy in distinguishing SDHx versus non-SDHx-related tumors (sensitivity/specificity: 100/100%). Moreover, the quantification of succinate could be considered a diagnostic alternative for assessing SDHx-related mutations of unknown pathogenicity. We were also able, for the first time, to uncover an SDH-like pattern in the two CTr-related PGLs. The present study demonstrates that HRMAS-NMR provides important information for SDHx-related PHEO/PGL characterization. Besides the high succinate-low glutamate hallmark, SDHx tumors also exhibit high values of methionine, a finding consistent with the hypermethylation pattern of these tumors. We also found important levels of glutamine, suggesting that glutamine metabolism might be involved in the pathogenesis of SDHx-related PHEOs/PGLs.
C1 [Imperiale, Alessio; Battini, Stephanie; Namer, Izzie-Jacques] Haukeland Hosp, Hautepierre Hosp, Dept Biophys & Nucl Med, F-67098 Strasbourg, France.
[Imperiale, Alessio; Moussallieh, Franois-Marie; Battini, Stephanie; Elbayed, Karim; Namer, Izzie-Jacques] Univ Strasbourg, ICube, UMR 7357, Strasbourg, France.
[Imperiale, Alessio; Moussallieh, Franois-Marie; Battini, Stephanie; Elbayed, Karim; Namer, Izzie-Jacques] FMTS, Fac Med, Strasbourg, France.
[Roche, Philippe] ISCB, Marseille, France.
[Roche, Philippe] Aix Marseille Univ UM105, INT 3D Mol Modeling Platform, CNRS, INSERM U1068,UMR7258,Canc Res Ctr,Inst Paoli Clam, Marseille, France.
[Cicek, A. Ercument] Carnegie Mellon Univ, Lane Ctr Computat Biol, Sch Comp Sci, Pittsburgh, PA USA.
[Sebag, Frederic] Aix Marseille Univ, La Timone Univ Hosp, Dept Endocrine Surg, Marseille, France.
[Brunaud, Laurent] Brabois Univ Hosp, Dept Digest Hepatobiliary & Endocrine Surg, Nancy, France.
[Barlier, Anne] Aix Marseille Univ, Concept Hosp, Lab Biochem & Mol Biol, Marseille, France.
[Loundou, Anderson] Aix Marseille Univ, Dept Publ Hlth, Marseille, France.
[Bachellier, Philippe] Univ Hosp, Hautepierre Hosp, Dept Visceral Surg & Transplantat, Strasbourg, France.
[Goichot, Bernard] Univ Hosp, Hautepierre Hosp, Dept Internal Med Diabet & Metab, Strasbourg, France.
[Stratakis, Constantine A.] NICHHD, Sect Genet & Endocrinol SEGEN, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 USA.
[Pacak, Karel] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Taieb, david] Aix Marseille Univ, La Timone Univ Hosp, European Ctr Res Med Imaging, Marseille, France.
RP Imperiale, A (reprint author), Haukeland Hosp, Dept Biophys & Nucl Med, 1 Ave Moliere, F-67098 Strasbourg, France.
EM alessio.imperiale@chru-strasbourg.fr
RI Battini, Stephanie/M-2575-2013;
OI Battini, Stephanie/0000-0003-0839-4553; Barlier,
Anne/0000-0002-3740-6173
FU Region Alsace; Oseo; Communaute Urbaine de Strasbourg; Conseil
Departemental du Bas-Rhin; Bruker BioSpin; University of Strasbourg;
Strasbourg University Hospital
FX This work is part of the CARMeN project and was supported by grants from
Region Alsace, Oseo, Communaute Urbaine de Strasbourg, Conseil
Departemental du Bas-Rhin, Bruker BioSpin, University of Strasbourg, and
Strasbourg University Hospital.
NR 37
TC 9
Z9 9
U1 1
U2 12
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 JAN
PY 2015
VL 17
IS 1
BP 55
EP 65
DI 10.1016/j.neo.2014.10.010
PG 11
WC Oncology
SC Oncology
GA AZ8IG
UT WOS:000348458300005
PM 25622899
ER
PT J
AU El Haj, M
Antoine, P
Kapogiannis, D
AF El Haj, Mohamad
Antoine, Pascal
Kapogiannis, Dimitrios
TI Similarity between remembering the past and imagining the future in
Alzheimer's disease: Implication of episodic memory
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Alzheimer's disease; Episodic memory; Future thinking; Imagination
ID SELF-DEFINING MEMORIES; MILD COGNITIVE IMPAIRMENT; MENTAL TIME-TRAVEL;
AUTOBIOGRAPHICAL MEMORY; AUTONOETIC CONSCIOUSNESS; NEURODEGENERATIVE
DISEASES; DEPRESSION SCALE; HOSPITAL ANXIETY; DEFAULT-MODE; DEMENTIA
AB Recent studies suggest that common cognitive processes and neuroanatomical substrates underlie the ability to remember the past and imagine the future. We studied these cognitive processes in patients with Alzheimer's Disease (AD). We asked 27 participants with AD and 30 older controls, matched by age, sex, and educational level, to generate past and future autobiographical events. Autobiographical generation was analyzed with respect to theme, general autobiographical performance, contextual performance, self-defining memories, and autonoetic reliving/re-experiencing. Unlike older controls, most AD participants evoked similar themes when generating past and future events (n=23/30 participants). These participants also showed similar autobiographical and contextual performance, similar amount of self-defining memories, and similar autonoetic states when generating past and future events. Further, significant correlations were detected between hippocampal-dependent memory decline in AD participants and their ability to relive past and future events. These outcomes suggest striking similarities between remembering the past and imagining the future in AD. Due to their memory decline, imagining the future in AD patients is likely to draw heavily from the little amount of available information from past episodes, resulting in striking similarities between remembering the past and imagining the future. Finally, and unlike AD participants, older controls mentally "try out" alternative approaches to upcoming situations without replicating the same schemes of past events. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [El Haj, Mohamad; Antoine, Pascal] Univ North France, Res Unit Cognit & Affect Sci URECA EA1059, Lille, France.
[El Haj, Mohamad; Antoine, Pascal] Univ North France, Dept Psychol, UMR SCALAB, Lille, France.
[Kapogiannis, Dimitrios] NIA, Neurosci Lab, Baltimore, MD USA.
RP El Haj, M (reprint author), Univ Lille 3, Dept Psychol, BP 59653, Villeneuve Dascq, France.
EM mohamad.elhaj@univ-lille3.fr
OI el haj, mohamad/0000-0001-7635-7557
FU LABEX (Excellence Laboratory, Program Investment for the Future)
DIS-TALZ (Development of Innovative Strategies for a Transdisciplinary
Approach to Alzheimer Disease); National Institute on Aging/National
Institutes of Health
FX Dr. El Haj and Dr. Antoine were supported by the LABEX (Excellence
Laboratory, Program Investment for the Future) DIS-TALZ (Development of
Innovative Strategies for a Transdisciplinary Approach to Alzheimer
Disease). This research was supported in part by the Intramural Research
Program of the National Institute on Aging/National Institutes of Health
(Dimitrios Kapogiannis).
NR 63
TC 16
Z9 16
U1 6
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD JAN
PY 2015
VL 66
BP 119
EP 125
DI 10.1016/j.neuropsychologia.2014.11.015
PG 7
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA CA0SG
UT WOS:000348626200013
PM 25448861
ER
PT J
AU Kandi, SK
Manohar, S
Gerena, CEV
Zayas, B
Malhotra, SV
Rawat, DS
AF Kandi, Shamseer Kulangara
Manohar, Sunny
Gerena, Christian E. Velez
Zayas, Beatriz
Malhotra, Sanjay V.
Rawat, Diwan S.
TI C-5-curcuminoid-4-aminoquinoline based molecular hybrids: design,
synthesis and mechanistic investigation of anticancer activity
SO NEW JOURNAL OF CHEMISTRY
LA English
DT Article
ID CELL-CYCLE ARREST; IMPROVED IN-VITRO; CANCER-CHEMOTHERAPY; ANTIMALARIAL
ACTIVITY; ALKYLATING-AGENTS; CURCUMIN ANALOGS; APOPTOSIS;
BIOAVAILABILITY; ANTIMETABOLITES; INDUCTION
AB The privileged scaffolds of curcumin and 4-aminoquinolines are extensively used in the design and synthesis of biodynamic agents having remarkable efficacy against diseases like cancer and malaria. Therefore, we anticipated that covalent hybridization of these two pharmacophores via the triazole linker may lead to molecules with better anticancer activity. The synthesized hybrid compounds were tested for their anti-cancer activity on 60 human cancer cell lines, which represent diverse histologies. Our study has identified a set of these hybrids that showed excellent growth inhibition at nano-molar concentrations. The mechanistic investigations through a series of assays showed apoptotic induction as a cause for their displayed anticancer activity.
C1 [Kandi, Shamseer Kulangara; Manohar, Sunny; Rawat, Diwan S.] Univ Delhi, Dept Chem, Delhi 110007, India.
[Gerena, Christian E. Velez; Zayas, Beatriz] Univ Metropolitana, Sch Environm Affairs, San Juan, PR 00928 USA.
[Malhotra, Sanjay V.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Lab Synthet Chem, Frederick, MD 21702 USA.
RP Malhotra, SV (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Lab Synthet Chem, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov; dsrawat@chemistry.du.ac.in
FU University Grant Commission, New Delhi, India [41-202/2012 (SR)]; DU-DST
PURSE, University of Delhi, Delhi, India; CSIR; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]
FX DSR acknowledges University Grant Commission [41-202/2012 (SR)], New
Delhi, India and DU-DST PURSE, University of Delhi, Delhi, India for
financial support. S. K. K. and S. M. are thankful to CSIR for the award
of junior and senior research fellowship. S. V. M. would like to
acknowledge the support from National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E. Authors are
also thankful to CIF-USIC, University of Delhi, Delhi for NMR spectral
data and RSIC, CDRI, Lucknow for mass data. We thank Alfredo Blakeley,
Julie Early, Stephanie Florio, and Juliane Ollinger for technical
assistance.
NR 55
TC 7
Z9 7
U1 0
U2 6
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1144-0546
EI 1369-9261
J9 NEW J CHEM
JI New J. Chem.
PD JAN
PY 2015
VL 39
IS 1
BP 224
EP 234
DI 10.1039/c4nj00936c
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA AZ6LS
UT WOS:000348331900030
ER
PT J
AU Bates, SE
AF Bates, Susan E.
TI Central Nervous System Metastasis From Breast Cancer
SO ONCOLOGIST
LA English
DT Editorial Material
ID BRAIN METASTASES; EFFICACY; BARRIER; PLUS
C1 [Bates, Susan E.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bates, SE (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 12N226, Bethesda, MD 20892 USA.
EM batess@helix.nih.gov
NR 11
TC 2
Z9 2
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD JAN
PY 2015
VL 20
IS 1
BP 3
EP 4
DI 10.1634/theoncologist.2014-0469
PG 2
WC Oncology
SC Oncology
GA AZ8IO
UT WOS:000348459100002
PM 25542449
ER
PT J
AU Leclezio, L
Jansen, A
Whittemore, VH
de Vries, PJ
AF Leclezio, Loren
Jansen, Anna
Whittemore, Vicky H.
de Vries, Petrus J.
TI Pilot Validation of the Tuberous Sclerosis-Associated Neuropsychiatric
Disorders (TAND) Checklist
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE tuberous sclerosis complex; TAND; autism; mental health;
neuropsychology; cognition; academic; psychosocial
ID COMPLEX CONSENSUS CONFERENCE; DIAGNOSTIC-CRITERIA; ATTENTION DEFICITS;
POPULATION; BEHAVIOR; RECOMMENDATIONS; IDENTIFICATION; CHILDREN; SAMPLE;
GENE
AB BACKGROUND: Tuberous sclerosis complex is a multisystem disorder that includes a range of tuberous sclerosis associated neuropsychiatric disorders (TAND). The lifetime prevalence rates of TAND are very high; yet surveys suggest that the majority of individuals with tuberous sclerosis never receive appropriate assessment or treatment for TAND. To aid systematic enquiry, a TAND Checklist was developed. Here, we performed pilot validation of the TAND Checklist. METHOD: Mixed methods were used across two stages. In stage 1, we gathered feedback on the Checklist from tuberous sclerosis "expert professionals" and "expert parents and caregivers." The aim was to examine face and content validity. Stage 2 involved the administration of the refined TAND Checklist to 20 parents of individuals with tuberous sclerosis concurrently with four widely used validated rating scales, to examine external validity and obtain qualitative feedback on face-to-face administration of the TAND Checklist. RESULTS: Twenty professionals and 62 parents and caregivers from 28 countries participated in the pilot. The TAND Checklist demonstrated good face and content validity with high overall mean and median scores. Qualitative analysis highlighted concerns about the likely use of the TAND Checklist, suggesting that family members and individuals with tuberous sclerosis should drive usage. Stage 2 results showed moderate-to-very good external validity across TAND domain and key subdomains. Internal consistency of domains and subdomains was acceptable to very good. Ninety-three percent of all participants (93%) reported four or more lifetime TAND behavioral difficulties. CONCLUSION: The pilot validation suggested that the TAND Checklist could provide a useful screening tool in clinical settings.
C1 [Leclezio, Loren; de Vries, Petrus J.] Univ Cape Town, Div Child & Adolescent Psychiat, Dept Psychiat & Mental Hlth, ZA-7700 Cape Town, South Africa.
[Jansen, Anna] Vrije Univ Brussel, UZ Brussel, Dept Pediat, Pediat Neurol Unit, Brussels, Belgium.
[Whittemore, Vicky H.] NINDS, NIH, Bethesda, MD 20892 USA.
RP de Vries, PJ (reprint author), Univ Cape Town, Div Child & Adolescent Psychiat, 46 Sawkins Rd, ZA-7700 Cape Town, South Africa.
EM petrus.devries@uct.ac.za
RI Jansen, Anna/P-3121-2014
OI Jansen, Anna/0000-0002-3835-2824
FU Australasian Tuberous Sclerosis Society; Tuberous Sclerosis
International; National Research Foundation; Struengmann Fund;
University of Cape Town; Tuberous Sclerosis Alliance
FX We are grateful to all expert professionals, expert parents, caregivers,
and individuals with TSC who participated in this study. A particular
thanks to the Australasian Tuberous Sclerosis Society and Tuberous
Sclerosis International for support. The study was supported by funding
from the National Research Foundation, Struengmann Fund, University of
Cape Town, and the Tuberous Sclerosis Alliance.
NR 42
TC 9
Z9 9
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD JAN
PY 2015
VL 52
IS 1
BP 16
EP 24
DI 10.1016/j.pediatrneurol.2014.10.006
PG 9
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA AZ7QA
UT WOS:000348411800003
PM 25499093
ER
PT J
AU de Vries, PJ
Whittemore, VH
Leclezio, L
Byars, AW
Dunn, D
Ess, KC
Hook, D
King, BH
Sahin, M
Jansen, A
AF de Vries, Petrus J.
Whittemore, Vicky H.
Leclezio, Loren
Byars, Anna W.
Dunn, David
Ess, Kevin C.
Hook, Dena
King, Bryan H.
Sahin, Mustafa
Jansen, Anna
TI Tuberous Sclerosis Associated Neuropsychiatric Disorders (TAND) and the
TAND Checklist
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE behavior; psychiatric disorders; autism; mental health; neurocognition;
learning disorders; neuropsychological; psycho-social
ID COMPLEX CONSENSUS CONFERENCE; SPORADIC LYMPHANGIOLEIOMYOMATOSIS;
SIROLIMUS THERAPY; SAMPLE; TRIAL; RECOMMENDATIONS; ANGIOMYOLIPOMA;
QUESTIONNAIRE; MULTICENTER; ADOLESCENTS
AB BACKGROUND: Tuberous sclerosis complex is a multisystem genetic disorder with a range of physical manifestations that require evaluation, surveillance, and management. Individuals with tuberous sclerosis complex also have a range of behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial difficulties. These may represent the greatest burden of the disease. Around 90% of individuals with tuberous sclerosis complex will have some of these difficulties during their lifetime, yet only about 20% ever receive evaluation and treatment. The Neuropsychiatry Panel at the 2012 Tuberous Sclerosis Complex International Consensus Conference expressed concern about the significant "treatment gap" and about confusion regarding terminology relating to the biopsychosocial difficulties associated with tuberous sclerosis complex. METHODS: The Tuberous Sclerosis Complex Neuropsychiatry Panel coined the term TAND tuberous sclerosis complex-associated neuropsychiatric disorders to bring together these multidimensional manifestations of the disorder, and recommended annual screening for TAND. In addition, the Panel agreed to develop a TAND Checklist as a guide for screening. RESULTS: Here, we present an outline of the conceptualization of TAND, rationale for the structure of the TAND Checklist, and include the full US English version of the TAND Checklist. CONCLUSION: We hope that the unified term TAND and the TAND Checklist will raise awareness of the importance of tuberous sclerosis complex-associated neuropsychiatric disorders and of the major burden of disease associated with it, provide a shared language and a simple tool to describe and evaluate the different levels of TAND, alert clinical teams and families or individuals of the importance of screening, assessment, and treatment of TAND, and provide a shared framework for future studies of tuberous sclerosis complex-associated neuropsychiatric disorders.
C1 [de Vries, Petrus J.; Leclezio, Loren] Univ Cape Town, Div Child & Adolescent Psychiat, Dept Psychiat & Mental Hlth, ZA-7700 Cape Town, South Africa.
[Whittemore, Vicky H.] NINDS, NIH, Bethesda, MD 20892 USA.
[Byars, Anna W.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Dunn, David] Indiana Univ Sch Med, Riley Child & Adolescent Psychiat Clin, Indianapolis, IN 46202 USA.
[Ess, Kevin C.] Vanderbilt Univ, Ctr Med, Dept Pediat, Div Pediat Neurol, Nashville, TN 37232 USA.
[Hook, Dena] TB Sclerosis Alliance, Silver Spring, MD USA.
[King, Bryan H.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[King, Bryan H.] Seattle Childrens Hosp, Seattle, WA USA.
[Sahin, Mustafa] Boston Childrens Hosp, FM Kirby Ctr Neurosci, Dept Neurol, Boston, MA USA.
[Jansen, Anna] VUB, Dept Publ Hlth, UZ Brussel, Pediat Neurol Unit, Brussels, Belgium.
RP Whittemore, VH (reprint author), Univ Cape Town, Div Child & Adolescent Psychiat, 46 Sawkins Rd, ZA-7700 Cape Town, South Africa.
EM petrus.devries@uct.ac.za
RI Jansen, Anna/P-3121-2014;
OI Jansen, Anna/0000-0002-3835-2824; SAHIN, MUSTAFA/0000-0001-7044-2953
FU Tuberous Sclerosis Alliance; NRF; PERC; Struengmann Fund; NIH
[1U01NS082320-01]; Rothberg Institute for Childhood Diseases; Novartis
Pharmaceuticals; Sandra and Brian O'Brien; Questcor Pharmaceuticals
FX The 2012 International TSC Clinical Consensus Conference was organized
by the Tuberous Sclerosis Alliance. The conference was supported by
sponsors of the Tuberous Sclerosis Alliance without playing a role in
the planning or having a presence at the conference and the resulting
recommendations: the Rothberg Institute for Childhood Diseases, Novartis
Pharmaceuticals, Sandra and Brian O'Brien, and Questcor Pharmaceuticals.
P.J.d.V. receives support from NRF, PERC and the Struengmann Fund. MS.
receives support from the NIH 1U01NS082320-01.
NR 39
TC 28
Z9 28
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD JAN
PY 2015
VL 52
IS 1
BP 25
EP 35
DI 10.1016/j.pediatrneurol.2014.10.004
PG 11
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA AZ7QA
UT WOS:000348411800004
PM 25532776
ER
PT J
AU Beydoun, MA
Fanelli-Kuczmarski, MT
Kitner-Triolo, MH
Beydoun, HA
Kaufman, JS
Mason, MA
Evans, MK
Zonderman, AB
AF Beydoun, May A.
Fanelli-Kuczmarski, Marie T.
Kitner-Triolo, Melissa H.
Beydoun, Hind A.
Kaufman, Jay S.
Mason, Marc A.
Evans, Michele K.
Zonderman, Alan B.
TI Dietary Antioxidant Intake and Its Association With Cognitive Function
in an Ethnically Diverse Sample of US Adults
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE antioxidants; cognitive function; depressive symptoms; midlife
ID INCIDENT ALZHEIMER-DISEASE; MULTIPLE-PASS METHOD; POLYUNSATURATED
FATTY-ACIDS; C SUPPLEMENT USE; VITAMIN-E LEVELS; DEPRESSIVE SYMPTOMS;
OLDER-ADULTS; SOCIOECONOMIC-STATUS; OXIDATIVE STRESS; CACHE COUNTY
AB Background Dietary antioxidants can inhibit reactions accompanying neurodegeneration and thus prevent cognitive impairment. We describe associations of dietary antioxidants with cognitive function in a large biracial population, while testing moderation by sex, race, and age and mediation by depressive symptoms.
Methods This was a cross-sectional analysis of 1274 adults (541 men and 733 women) aged 30 to 64 years at baseline (mean [standard deviation] = 47.5 [9.3]) in the Healthy Aging in Neighborhoods of Diversity Across the Lifespan Study, Baltimore city, MD. Cognitive performance in the domains of memory, language/verbal, attention, spatial, psychomotor speed, executive function, and global mental status were assessed. The 20-item Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms. Dietary intake was assessed with two 24-hour recalls, estimating daily consumption of total carotenoids and vitamins A, C, and E per 1000 kcal.
Results Among key findings, 1 standard deviation (approximate to 2.02 mg/1000 kcal) higher vitamin E was associated with a higher score on verbal memory, immediate recall ( = +0.64 [0.19], p = .001), and better language/verbal fluency performance ( = +0.53 [0.16], p = .001), particularly among the younger age group. Women with higher vitamin E intake ( = +0.68 [0.21], p = .001) had better performance on a psychomotor speed test. The vitamin E-verbal memory association was partially mediated by depressive symptoms (proportion mediated = 13%-16%).
Conclusions In sum, future cohort studies and dietary interventions should focus on associations of dietary vitamin E with cognitive decline, specifically for domains of verbal memory, verbal fluency, and psychomotor speed.
C1 [Beydoun, May A.; Kitner-Triolo, Melissa H.; Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, IRP, Baltimore, MD 21224 USA.
[Fanelli-Kuczmarski, Marie T.] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Kaufman, Jay S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Mason, Marc A.] MedStar Res Inst, Stat Informat Syst, Baltimore, MD USA.
RP Beydoun, MA (reprint author), NIA, NIH Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Kaufman, Jay/0000-0003-1606-401X; Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging, Intramural Research Program (NIA/NIH/IRP)
FX This study was entirely supported by the National Institute on Aging,
Intramural Research Program (NIA/NIH/IRP). The authors declare no
conflict of interest.
NR 100
TC 2
Z9 2
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD JAN
PY 2015
VL 77
IS 1
BP 68
EP 82
DI 10.1097/PSY.0000000000000129
PG 15
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA AZ8WT
UT WOS:000348493100009
PM 25478706
ER
PT J
AU Desmond, R
Townsley, DM
Dunbar, C
Young, NS
AF Desmond, Ronan
Townsley, Danielle M.
Dunbar, Cynthia
Young, Neal S.
TI Eltrombopag in Aplastic Anemia
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; BONE-MARROW FAILURE;
ANTITHYMOCYTE GLOBULIN; LONG-TERM; IMMUNOSUPPRESSIVE THERAPY;
CYTOGENETIC ABNORMALITIES; MYELODYSPLASTIC SYNDROMES; GROWTH-FACTORS;
THROMBOPOIETIN
AB The treatment of aplastic anemia is currently with immunosuppressive therapy (IT) with anti-thymocyte globulin (ATG) and cyclosporine, to which two thirds of patients respond. However, a significant proportion of these responders relapse and many have persistent cytopenias. The management of these patients is challenging. Modifications to this standard approach using alternative immunosuppressive agents or adding hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) have not improved outcome. A recent trial has shown that eltrombopag, a thrombopoeitin mimetic, is efficacious in the treatment of patients with severe aplastic anemia (SAA) refractory to IST. There is evidence that this drug works by directly stimulating marrow stem and progenitor cells thereby promoting hematopoietic recovery in patients with bone marrow failure. Several trials are ongoing in our institution using this very promising drug in combination therapy in the upfront treatment of SAA, in IST-refractory SAA and in moderate disease. (C) Published by Elsevier Inc.
C1 [Desmond, Ronan] Tallaght Hosp, Dept Haematol, Dublin, Ireland.
[Desmond, Ronan; Townsley, Danielle M.; Dunbar, Cynthia; Young, Neal S.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Desmond, R (reprint author), Tallaght Hosp, Dept Haematol, Dublin, Ireland.
EM ronan.desmond@amnch.ie
FU Intramural NIH HHS [Z99 HL999999]
NR 45
TC 1
Z9 1
U1 1
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JAN
PY 2015
VL 52
IS 1
BP 31
EP 37
DI 10.1053/j.seminhematol.2014.10.002
PG 7
WC Hematology
SC Hematology
GA AZ2YO
UT WOS:000348095400006
PM 25578417
ER
PT J
AU Kozak, CA
AF Kozak, Christine A.
TI Origins of the Endogenous and Infectious Laboratory Mouse
Gammaretroviruses
SO VIRUSES-BASEL
LA English
DT Review
DE mouse endogenous retroviruses; mouse leukemia viruses; house mouse
subspecies; ecotropic/xenotropic/polytropic gammaretroviruses;
retrovirus restriction factors; recombinant mouse gammaretroviruses
ID MURINE-LEUKEMIA-VIRUS; CELL-SURFACE RECEPTOR; LONG TERMINAL REPEATS;
FOCUS-FORMING VIRUS; ECOTROPIC RETROVIRUS RECEPTOR;
MUS-MUSCULUS-MOLOSSINUS; GROWTH IN-VIVO; C-TYPE VIRUSES; CAS-BR-E; AKR/J
MICE
AB The mouse gammaretroviruses associated with leukemogenesis are found in the classical inbred mouse strains and in house mouse subspecies as infectious exogenous viruses (XRVs) and as endogenous retroviruses (ERVs) inserted into their host genomes. There are three major mouse leukemia virus (MuLV) subgroups in laboratory mice: ecotropic, xenotropic, and polytropic. These MuLV subgroups differ in host range, pathogenicity, receptor usage and subspecies of origin. The MuLV ERVs are recent acquisitions in the mouse genome as demonstrated by the presence of many full-length nondefective MuLV ERVs that produce XRVs, the segregation of these MuLV subgroups into different house mouse subspecies, and by the positional polymorphism of these loci among inbred strains and individual wild mice. While some ecotropic and xenotropic ERVs can produce XRVs directly, others, especially the pathogenic polytropic ERVs, do so only after recombinations that can involve all three ERV subgroups. Here, I describe individual MuLV ERVs found in the laboratory mice, their origins and geographic distribution in wild mouse subspecies, their varying ability to produce infectious virus and the biological consequences of this expression.
C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA.
EM ckozak@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, NIH
FX The work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 199
TC 5
Z9 5
U1 4
U2 13
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD JAN
PY 2015
VL 7
IS 1
BP 1
EP 26
DI 10.3390/v7010001
PG 26
WC Virology
SC Virology
GA AZ7LY
UT WOS:000348401600001
ER
PT J
AU Baker, EH
Sloan, JL
Hauser, NS
Gropman, AL
Adams, DR
Toro, C
Manoli, I
Venditti, CP
AF Baker, E. H.
Sloan, J. L.
Hauser, N. S.
Gropman, A. L.
Adams, D. R.
Toro, C.
Manoli, I.
Venditti, C. P.
TI MRI Characteristics of Globus Pallidus Infarcts in Isolated
Methylmalonic Acidemia
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID NIGRA PARS RETICULATA; SUBSTANTIA-NIGRA; BASAL GANGLIA; DYSFUNCTION;
MANAGEMENT; ACIDURIA; PRIMATES
AB BACKGROUND: Bilateral infarcts confined to the globus pallidus are unusual and occur in conjunction with only a few disorders, including isolated methylmalonic acidemia, a heterogeneous inborn error of metabolism. On the basis of neuroradiographic features of metabolic strokes observed in a large cohort of patients with methylmalonic acidemia, we have devised a staging system for methylmalonic acidemia related globus pallidus infarcts.
MATERIALS AND METHODS: Forty patients with isolated methylmalonic acidemia and neurologic symptoms underwent clinical brain MR imaging studies, which included 3D-T1WI. Infarcted globus pallidus segments were neuroanatomically characterized, and infarct volumes were measured.
RESULTS: Globus pallidus infarcts were present in 19 patients; all were bilateral, and most were left-dominant. A neuroanatomic scoring system based on the infarct patterns was devised; this revealed a 5-stage hierarchical susceptibility to metabolic infarct, with the posterior portion of the globus pallidus externa being the most vulnerable. Globus pallidus infarct prevalence by methylmalonic acidemia class was the following: cblA (5/7, 71%), cblB (3/7, 43%), mut(o) (10/22, 45%), and mut- (1/4, 25%). Tiny lacunar infarcts in the pars reticulata of the substantia nigra, previously unrecognized in methylmalonic acidemia, were found in 17 patients, 13 of whom also had a globus pallidus infarct.
CONCLUSIONS: The staged pattern of globus pallidus infarcts in isolated methylmalonic acidemia suggests a nonuniform, regionally specific cellular susceptibility to metabolic injury, even for patients having milder biochemical phenotypes. In support of this hypothesis, the delineation of lacunar infarcts in the pars reticulata of the substantia nigra, a tissue functionally and histologically identical to the globus pallid us interna, supports the concept of cell-specific pathology.
C1 [Baker, E. H.] NHGRI, Dept Radiol & Imaging Sci, NIH, Bethesda, MD 20892 USA.
[Sloan, J. L.; Manoli, I.; Venditti, C. P.] NHGRI, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Sloan, J. L.; Manoli, I.; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Adams, D. R.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Toro, C.] NHGRI, Undiagnosed Dis Program, NIH, Bethesda, MD 20892 USA.
[Hauser, N. S.] Childrens Hosp Cent Calif, Med Genet & Metab Dept, Madera, CA USA.
[Gropman, A. L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
RP Baker, EH (reprint author), 10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA.
EM bakere@mail.nih.gov
OI Manoli, Irini/0000-0003-1543-2941
FU Intramural Research Program of the National Human Genome Research
Institute (National Institutes of Health) [04-HG-0127]
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute (National Institutes of Health
protocol 04-HG-0127 "Clinical and Basic Investigations of Methylmalonic
Acidemia and Related Disorders," clinicaltrials.gov identifier
NCT00078078).
NR 32
TC 5
Z9 6
U1 1
U2 4
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD JAN
PY 2015
VL 36
IS 1
BP 194
EP 201
DI 10.3174/ajnr.A4087
PG 8
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA AZ1ON
UT WOS:000348008200033
PM 25190203
ER
PT J
AU Jairath, S
Sukumaran, N
Madhavan, P
Natarajan, B
Chandrashekharan, U
Jayaschandran, V
Leung, S
Ali, N
Basu, A
Bhaskaran, M
Molmenti, E
AF Jairath, Sapna
Sukumaran, Neenu
Madhavan, Parvathy
Natarajan, Balaji
Chandrashekharan, Umashankar
Jayaschandran, Vivek
Leung, Sam
Ali, Nicole
Basu, Amit
Bhaskaran, Madhu
Molmenti, Ernesto
TI Pre-Transplant Plasmapheresis Allows Long-Term Allograft Survival in
Renal Transplant Recipients With Donor Specific Antibodies
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT 15th Annual State of the Art Winter Symposium of the
American-Society-of-Transplant-Surgeons (ASTS)
CY JAN 15-18, 2015
CL Miami, FL
SP Amer Soc Transplant Surg
C1 [Jairath, Sapna; Sukumaran, Neenu; Madhavan, Parvathy; Chandrashekharan, Umashankar; Jayaschandran, Vivek; Leung, Sam; Ali, Nicole; Basu, Amit; Bhaskaran, Madhu; Molmenti, Ernesto] North Shore LIJ Hlth Syst, Manhasset, NY USA.
[Natarajan, Balaji] 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JAN
PY 2015
VL 15
SU 1
SI SI
MA P-71
BP 81
EP 81
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AZ1YF
UT WOS:000348030600099
ER
PT J
AU Bailey, JA
Pablo, J
Niangaly, A
Travassos, MA
Ouattara, A
Coulibaly, D
Laurens, MB
Takala-Harrison, SL
Lyke, KE
Skinner, J
Berry, AA
Jasinskas, A
Nakajima-Sasaki, R
Kouriba, B
Thera, MA
Felgner, PL
Doumbo, OK
Plowe, CV
AF Bailey, Jason A.
Pablo, Jozelyn
Niangaly, Amadou
Travassos, Mark A.
Ouattara, Amed
Coulibaly, Drissa
Laurens, Matthew B.
Takala-Harrison, Shannon L.
Lyke, Kirsten E.
Skinner, Jeff
Berry, Andrea A.
Jasinskas, Algis
Nakajima-Sasaki, Rie
Kouriba, Bourema
Thera, Mahamadou A.
Felgner, Philip L.
Doumbo, Ogobara K.
Plowe, Christopher V.
TI Short Report: Seroreactivity to a Large Panel of Field-Derived
Plasmodium falciparum Apical Membrane Antigen 1 and Merozoite Surface
Protein 1 Variants Reflects Seasonal and Lifetime Acquired Responses to
Malaria
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ALLELE-SPECIFIC EFFICACY; MALIAN ADULTS;
VACCINE; IMMUNOGENICITY; INFECTION; CHILDREN; SAFETY; MICROARRAYS
AB Parasite antigen diversity poses an obstacle to developing an effective malaria vaccine. A protein microarray containing Plasmodium falciparum apical membrane antigen 1 (AMA1, n = 57) and merozoite surface protein 1 19-kD (MSP1(19), n = 10) variants prevalent at a malaria vaccine testing site in Bandiagara, Mali, was used to assess changes in seroreactivity caused by seasonal and lifetime exposure to malaria. Malian adults had significantly higher magnitude and breadth of seroreactivity to variants of both antigens than did Malian children. Seroreactivity increased over the course of the malaria season in children and adults, but the difference was more dramatic in children. These results help to validate diversity-covering protein microarrays as a promising tool for measuring the breadth of antibody responses to highly variant proteins, and demonstrate the potential of this new tool to help guide the development of malaria vaccines with strain-transcending efficacy.
C1 [Plowe, Christopher V.] Univ Maryland, Sch Med, Howard Hughes Med Inst, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.
NIH, Immunogenet Lab, Bethesda, MD 20892 USA.
Univ Sci Tech & Technol, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Bamako, Mali.
[Bailey, Jason A.; Travassos, Mark A.; Ouattara, Amed; Laurens, Matthew B.; Takala-Harrison, Shannon L.; Lyke, Kirsten E.; Plowe, Christopher V.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Pablo, Jozelyn; Jasinskas, Algis; Nakajima-Sasaki, Rie; Felgner, Philip L.] Univ Calif Irvine, Div Infect Dis, Irvine, CA USA.
[Niangaly, Amadou; Coulibaly, Drissa; Thera, Mahamadou A.] Univ Bamako, Fac Med, Malaria Res & Training Ctr Bamako, Bamako, Mali.
[Niangaly, Amadou; Coulibaly, Drissa; Thera, Mahamadou A.] Mali Univ Sci Tech & Technol Bamako, Malaria Res & Training Ctr, Bamako, Mali.
[Skinner, Jeff] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Kouriba, Bourema; Doumbo, Ogobara K.] Univ Sci Tech & Technol Bamako, Malaria Res & Training Ctr, Bamako, Mali.
RP Plowe, CV (reprint author), Univ Maryland, Sch Med, Howard Hughes Med Inst, Ctr Vaccine Dev, 685 West Baltimore St,HSF1 480, Baltimore, MD 21201 USA.
EM jbail006@umaryland.edu; jozelynp@gmail.com; niangaly@icermali.org;
aouattara@medicine.umaryland.edu; coulibalyd@icermali.org;
mlaurens@medicine.umaryland.edu; stakala@medicine.umaryland.edu;
klyke@medicine.umaryland.edu; skinnerj@niaid.nih.gov; ajasinsk@uci.edu;
rie3@uci.edu; kouriba@icermali.org; mthera@icermali.org;
okd@icermali.org; cplowe@medicine.umaryland.edu
RI Laurens, Matthew/E-7293-2013;
OI Laurens, Matthew/0000-0003-3874-581X; Skinner, Jeff/0000-0001-5697-0442
FU FIC NIH HHS [D43 TW001589]; NIAID NIH HHS [R01 AI095916]; NIGMS NIH HHS
[R25 GM055036]
NR 20
TC 7
Z9 7
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JAN
PY 2015
VL 92
IS 1
BP 9
EP 12
DI 10.4269/ajtmh.14-0140
PG 4
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AZ4GU
UT WOS:000348180600005
PM 25294612
ER
PT J
AU Gromowski, GD
Firestone, CY
Bustos-Arriaga, J
Whitehead, SS
AF Gromowski, Gregory D.
Firestone, Cai-Yen
Bustos-Arriaga, Jose
Whitehead, Stephen S.
TI Genetic and Phenotypic Properties of Vero Cell-Adapted Japanese
Encephalitis Virus SA14-14-2 Vaccine Strain Variants and a Recombinant
Clone, which Demonstrates Attenuation and Immunogenicity in Mice
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID WEST-NILE-VIRUS; ANTIBODY-MEDIATED NEUTRALIZATION; SA 14-14-2 VACCINE;
WILD-TYPE; ALPHA/BETA-INTERFERON; NUCLEOTIDE-SEQUENCE; NEPALESE
CHILDREN; MOLECULAR-BASIS; INFECTION; IMMUNIZATION
AB The live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine, produced in primary hamster kidney cells, is safe and effective. Past attempts to adapt this virus to replicate in cells that are more favorable for vaccine production resulted in mutations that significantly reduced immunogenicity. In this study, 10 genetically distinct Vero cell-adapted JEV SA14-14-2 variants were isolated and a recombinant wild-type JEV clone, modified to contain the JEV SA14-14-2 polyprotein amino acid sequence, was recovered in Vero cells. A single capsid protein mutation (S66L) was important for Vero cell-adaptation. Mutations were also identified that modulated virus sensitivity to type I interferon-stimulation in Vero cells. A subset of JEV SA14-14-2 variants and the recombinant clone were evaluated in vivo and exhibited levels of attenuation that varied significantly in suckling mice, but were avirulent and highly immunogenic in weanling mice and are promising candidates for the development of a second-generation, recombinant vaccine.
C1 [Gromowski, Gregory D.; Firestone, Cai-Yen; Bustos-Arriaga, Jose; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Gromowski, GD (reprint author), NIAID, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM gromowskig@niaid.nih.gov; cfirestone@niaid.nih.gov;
bustosarriagaj2@mail.nih.gov; swhitehead@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases Intramural
Research Program, National Institutes of Health
FX This work was supported by the National Institute of Allergy and
Infectious Diseases Intramural Research Program, National Institutes of
Health.
NR 66
TC 3
Z9 3
U1 1
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 JAN
PY 2015
VL 92
IS 1
BP 98
EP 107
DI 10.4269/ajtmh.14-0427
PG 10
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AZ4GU
UT WOS:000348180600021
PM 25311701
ER
PT J
AU Rao, HY
Wang, DJ
Yang, YH
He, Y
AF Rao, Hengyi
Wang, Danny Jiongjiong
Yang, Yihong
He, Yong
TI Neuroimaging of Brain Networks and Function
SO BIOMED RESEARCH INTERNATIONAL
LA English
DT Editorial Material
C1 [Rao, Hengyi] Univ Penn, Perelman Sch Med, Ctr Funct Neuroimaging, Dept Neurol, Philadelphia, PA 19104 USA.
[Wang, Danny Jiongjiong] Univ Calif Los Angeles, Ahmanson Lovelace Brain Mapping Ctr, Dept Neurol, Los Angeles, CA 90095 USA.
[Yang, Yihong] NIDA, Magnet Resonance Imaging & Spect Sect, Baltimore, MD 21224 USA.
[He, Yong] Beijing Normal Univ, Natl Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
[He, Yong] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.
RP Rao, HY (reprint author), Univ Penn, Perelman Sch Med, Ctr Funct Neuroimaging, Dept Neurol, Philadelphia, PA 19104 USA.
EM hengyi@mail.med.upenn.edu
NR 0
TC 0
Z9 0
U1 1
U2 3
PU HINDAWI PUBLISHING CORPORATION
PI NEW YORK
PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA
SN 2314-6133
EI 2314-6141
J9 BIOMED RES INT
JI Biomed Res. Int.
PY 2015
AR 509141
DI 10.1155/2015/509141
PG 2
WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Research & Experimental Medicine
GA AZ5YR
UT WOS:000348295000001
ER
PT J
AU Little, JW
Ford, A
Symons-Liguori, AM
Chen, ZM
Janes, K
Doyle, T
Xie, J
Luongo, L
Tosh, DK
Maione, S
Bannister, K
Dickenson, AH
Vanderah, TW
Porreca, F
Jacobson, KA
Salvemini, D
AF Little, Joshua W.
Ford, Amanda
Symons-Liguori, Ashley M.
Chen, Zhoumou
Janes, Kali
Doyle, Timothy
Xie, Jennifer
Luongo, Livio
Tosh, Dillip K.
Maione, Sabatino
Bannister, Kirsty
Dickenson, Anthony H.
Vanderah, Todd W.
Porreca, Frank
Jacobson, Kenneth A.
Salvemini, Daniela
TI Endogenous adenosine A(3) receptor activation selectively alleviates
persistent pain states
SO BRAIN
LA English
DT Article
DE adenosine; A(3)AR; chronic pain; spontaneous pain; rostral ventromedial
medulla
ID ANTIINFLAMMATORY PROPERTIES; CANNABINOID RECEPTOR; INTERNATIONAL UNION;
KINASE INHIBITOR; NEUROPATHIC PAIN; 1ST POTENT; RAT; AGONISTS; CELLS;
CLASSIFICATION
AB Adenosine's analgesic effects have previously been attributed to A(1) and A(2A) adenosine receptors. However, Little et al. now show that A(3) adenosine receptor activation by endogenous adenosine and potent agonists selectively suppresses persistent pain states by activating brain-to-spinal cord circuits that inhibit pain processing. Targeting A(3) receptors could help relieve chronic pain.Chronic pain is a global burden that promotes disability and unnecessary suffering. To date, efficacious treatment of chronic pain has not been achieved. Thus, new therapeutic targets are needed. Here, we demonstrate that increasing endogenous adenosine levels through selective adenosine kinase inhibition produces powerful analgesic effects in rodent models of experimental neuropathic pain through the A(3) adenosine receptor (A(3)AR, now known as ADORA3) signalling pathway. Similar results were obtained by the administration of a novel and highly selective A(3)AR agonist. These effects were prevented by blockade of spinal and supraspinal A(3)AR, lost in A(3)AR knock-out mice, and independent of opioid and endocannabinoid mechanisms. A(3)AR activation also relieved non-evoked spontaneous pain behaviours without promoting analgesic tolerance or inherent reward. Further examination revealed that A(3)AR activation reduced spinal cord pain processing by decreasing the excitability of spinal wide dynamic range neurons and producing supraspinal inhibition of spinal nociception through activation of serotonergic and noradrenergic bulbospinal circuits. Critically, engaging the A(3)AR mechanism did not alter nociceptive thresholds in non-neuropathy animals and therefore produced selective alleviation of persistent neuropathic pain states. These studies reveal A(3)AR activation by adenosine as an endogenous anti-nociceptive pathway and support the development of A(3)AR agonists as novel therapeutics to treat chronic pain.
C1 [Little, Joshua W.; Ford, Amanda; Chen, Zhoumou; Janes, Kali; Doyle, Timothy; Salvemini, Daniela] St Louis Univ, Sch Med, St Louis, MO USA.
[Symons-Liguori, Ashley M.; Xie, Jennifer; Vanderah, Todd W.; Porreca, Frank] Univ Arizona, Dept Pharmacol & Anesthesiol, Tucson, AZ USA.
[Luongo, Livio; Maione, Sabatino] Univ Naples 2, Dept Expt Med, Div Pharmacol, Naples, Italy.
[Tosh, Dillip K.; Jacobson, Kenneth A.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Bannister, Kirsty; Dickenson, Anthony H.] UCL, Dept Neurosci Physiol & Pharmacol, London, England.
RP Salvemini, D (reprint author), 1402 S Grand Ave, St Louis, MO 63104 USA.
EM salvemd@slu.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Cancer Institute [RO1CA169519]; NIH [5T32GM008306]; NIDDK
Intramural Research Program; FIRB "Futuro in Ricerca" MIUR, Italy
[RBFR126IGO_001]; Saint Louis Cancer Centre
FX This work was supported by grants from the National Cancer Institute
(RO1CA169519), NIH predoctoral fellowship (5T32GM008306), NIDDK
Intramural Research Program, FIRB "Futuro in Ricerca" MIUR, Italy
(RBFR126IGO_001) and with additional support from the Saint Louis Cancer
Centre.
NR 33
TC 29
Z9 31
U1 3
U2 13
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 JAN 1
PY 2015
VL 138
BP 28
EP 35
DI 10.1093/brain/awu330
PN 1
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AZ4KM
UT WOS:000348189800013
PM 25414036
ER
PT J
AU Senatorov, VV
Damadzic, R
Mann, CL
Schwandt, ML
George, DT
Hommer, DW
Heilig, M
Momenan, R
AF Senatorov, Vladimir V.
Damadzic, Ruslan
Mann, Claire L.
Schwandt, Melanie L.
George, David T.
Hommer, Daniel W.
Heilig, Markus
Momenan, Reza
TI Reduced anterior insula, enlarged amygdala in alcoholism and associated
depleted von Economo neurons
SO BRAIN
LA English
DT Article
DE insula; amygdala; von Economo neurons; alcoholism; MRI
ID CIGARETTE-SMOKING; SOCIAL EXCLUSION; DECISION-MAKING; BRAIN VOLUMES;
DEPENDENCE; CORTEX; SCHIZOPHRENIA; ADDICTION; CONNECTIVITY; REDUCTION
AB The insula, a structure involved in higher order representation of interoceptive states, has recently been implicated in drug craving and social stress. Here, we performed brain magnetic resonance imaging to measure volumes of the insula and amygdala, a structure with reciprocal insular connections, in 26 alcohol-dependent patients and 24 healthy volunteers (aged 22-56 years, nine females in each group). We used an established morphometry method to quantify total and regional insular volumes. Volumetric measurements of the amygdala were obtained using a model-based segmentation/ registration tool. In alcohol-dependent patients, anterior insula volumes were bilaterally reduced compared to healthy volunteers (left by 10%, right by 11%, normalized to total brain volumes). Furthermore, alcohol-dependent patients, compared with healthy volunteers, had bilaterally increased amygdala volumes. The left amygdala was increased by 28% and the right by 29%, normalized to total brain volumes. Postmortem studies of the anterior insula showed that the reduced anterior insular volume may be associated with a population of von Economo neurons, which were 60% diminished in subjects with a history of alcoholism (n = 6) as compared to subjects without a history of alcoholism (n = 6) (aged 32-56 years, all males). The pattern of neuroanatomical change observed in our alcoholdependent patients might result in a loss of top-down control of amygdala function, potentially contributing to impaired social cognition as well as an inability to control negatively reinforced alcohol seeking and use.
C1 [Senatorov, Vladimir V.; Mann, Claire L.; Hommer, Daniel W.; Momenan, Reza] NIAAA, Sect Brain Elect & Imaging, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Damadzic, Ruslan; Schwandt, Melanie L.; George, David T.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
RP Momenan, R (reprint author), NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,MSC 1108, Bethesda, MD 20892 USA.
EM rezam@nih.gov
RI Schwandt, Melanie/L-9866-2016
FU NIH, NIAAA
FX This research was supported by the Intramural Research Program of the
NIH, NIAAA.
NR 48
TC 5
Z9 6
U1 0
U2 8
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 JAN 1
PY 2015
VL 138
BP 69
EP 79
DI 10.1093/brain/awu305
PN 1
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AZ4KM
UT WOS:000348189800017
PM 25367022
ER
PT J
AU Horne, HN
Devi, CRB
Sung, H
Tang, TS
Rosenberg, PS
Hewitt, SM
Sherman, ME
Anderson, WF
Yang, XHR
AF Horne, Hisani N.
Devi, C. R. Beena
Sung, Hyuna
Tang, Tieng Swee
Rosenberg, Philip S.
Hewitt, Stephen M.
Sherman, Mark E.
Anderson, William F.
Yang, Xiaohong R.
TI Greater absolute risk for all subtypes of breast cancer in the US than
Malaysia
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Intrinsic subtypes; SEER; Incidence rates
ID PREVALENCE; DISPARITIES; CHINESE; WOMEN
AB Hormone receptor (HR) negative breast cancers are relatively more common in low-risk than high-risk countries and/or populations. However, the absolute variations between these different populations are not well established given the limited number of cancer registries with incidence rate data by breast cancer subtype. We, therefore, used two unique population-based resources with molecular data to compare incidence rates for the 'intrinsic' breast cancer subtypes between a low-risk Asian population in Malaysia and high-risk non-Hispanic white population in the National Cancer Institute's surveillance, epidemiology, and end results 18 registries database (SEER 18). The intrinsic breast cancer subtypes were recapitulated with the joint expression of the HRs (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor-2 (HER2). Invasive breast cancer incidence rates overall were fivefold greater in SEER 18 than in Malaysia. The majority of breast cancers were HR-positive in SEER 18 and HR-negative in Malaysia. Notwithstanding the greater relative distribution for HR-negative cancers in Malaysia, there was a greater absolute risk for all subtypes in SEER 18; incidence rates were nearly 7-fold higher for HR-positive and 2-fold higher for HR-negative cancers in SEER 18. Despite the well-established relative breast cancer differences between low-risk and high-risk countries and/or populations, there was a greater absolute risk for HR-positive and HR-negative subtypes in the US than Malaysia. Additional analytical studies are sorely needed to determine the factors responsible for the elevated risk of all subtypes of breast cancer in high-risk countries like the United States.
C1 [Horne, Hisani N.; Sung, Hyuna; Rosenberg, Philip S.; Anderson, William F.; Yang, Xiaohong R.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Devi, C. R. Beena; Tang, Tieng Swee] Sarawak Gen Hosp, Dept Radiotherapy Oncol & Palliat Care, Kuching, Sarawak, Malaysia.
[Hewitt, Stephen M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
[Yang, Xiaohong R.] NCI, DCEG, GEB, NIH, Bethesda, MD 20892 USA.
RP Yang, XHR (reprint author), NCI, DCEG, GEB, NIH, 9609 Med Ctr Dr Rm 6E426,MSC 9769, Bethesda, MD 20892 USA.
EM royang@mail.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU NIH, NCI, DCEG
FX We would like to thank the Pathology Department of Sarawak General
Hospital and Ms. Rokia Iren for their assistance in tissue block
retrieval. Research support Intramural Research Program of the NIH, NCI,
DCEG.
NR 24
TC 2
Z9 2
U1 3
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JAN
PY 2015
VL 149
IS 1
BP 285
EP 291
DI 10.1007/s10549-014-3243-9
PG 7
WC Oncology
SC Oncology
GA AZ4IB
UT WOS:000348183700031
PM 25537643
ER
PT J
AU Shaitelman, SF
Cromwell, KD
Rasmussen, JC
Stout, NL
Armer, JM
Lasinski, BB
Cormier, JN
AF Shaitelman, Simona F.
Cromwell, Kate D.
Rasmussen, John C.
Stout, Nicole L.
Armer, Jane M.
Lasinski, Bonnie B.
Cormier, Janice N.
TI Recent Progress in the Treatment and Prevention of Cancer-Related
Lymphedema
SO CA-A CANCER JOURNAL FOR CLINICIANS
LA English
DT Review
DE lymphedema; morbidities; treatment; diagnosis
ID QUALITY-OF-LIFE; LOWER-LIMB LYMPHEDEMA; SENTINEL-NODE BIOPSY;
NEAR-INFRARED FLUORESCENCE; LOWER-EXTREMITY LYMPHEDEMA; PROSPECTIVE
SURVEILLANCE MODEL; REVERSE MAPPING ARM; PREOPERATIVE ASSESSMENT
ENABLES; INTRAVASCULAR STENTING METHOD; LYMPHATIC VENOUS ANASTOMOSIS
AB This article provides an overview of the recent developments in the diagnosis, treatment, and prevention of cancer-related lymphedema. Lymphedema incidence by tumor site is evaluated. Measurement techniques and trends in patient education and treatment are also summarized to include current trends in therapeutic and surgical treatment options as well as longer-term management. Finally, an overview of the policies related to insurance coverage and reimbursement will give the clinician an overview of important trends in the diagnosis, treatment, and management of cancer-related lymphedema. CA Cancer J Clin 2015;65:55-81. (c) 2014 American Cancer Society.
C1 [Shaitelman, Simona F.] Univ Texas MD Anderson Canc Ctr, Dept Breast Radiat Oncol, Div Radiat Oncol, Houston, TX 77030 USA.
[Cromwell, Kate D.; Cormier, Janice N.] Univ Texas MD Anderson Canc Ctr, Div Surg, Dept Surg Oncol, Houston, TX 77030 USA.
[Rasmussen, John C.] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
[Stout, Nicole L.; Lasinski, Bonnie B.] NIH, Off Strateg Res, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Armer, Jane M.] Univ Missouri, Sinclair Sch Nursing, Ellis Fischel Canc Ctr, Columbia, MO USA.
[Lasinski, Bonnie B.] Lymphedema Therapy & Boris Lasinski Sch, Woodbury, NY USA.
RP Cormier, JN (reprint author), Univ Texas MD Anderson Canc Ctr, Div Surg, Dept Surg Oncol, Unit 1484, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM jcormier@mdanderson.org
FU National Institutes of Health through The University of Texas MD
Anderson Cancer Center [CA016672]; Elekta; MD Anderson Physicians
Network; National Institutes of Health; NIRF Imaging
FX Supported in part by the National Institutes of Health through The
University of Texas MD Anderson Cancer Center Support Grant CA016672.
Dr. Shaitelman has received a grant from Elekta and has acted as a paid
consultant for the MD Anderson Physicians Network for work performed
outside of the current study. Dr. Rasmussen has received a grant from
the National Institutes of Health for the development of near-infrared
fluorescence imaging for work performed as part of the current study and
has acted as a paid consultant for NIRF Imaging for work performed
outside of the current study. In addition, Dr. Rasmussen has patents for
Method of Measuring Propulsion in Lymphatic Structures and Functional
Near-Infrared Fluorescence Lymphatic Mapping for Diagnosing, Accessing,
Monitoring and Directing Therapy of Lymphatic Disorders, both of which
are licensed to NIRF Imaging and controlled by UTHealth. The remaining
authors report no conflicts of interest.
NR 245
TC 16
Z9 16
U1 1
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-9235
EI 1542-4863
J9 CA-CANCER J CLIN
JI CA-Cancer J. Clin.
PD JAN-FEB
PY 2015
VL 65
IS 1
BP 55
EP 81
DI 10.3322/caac.21253
PG 27
WC Oncology
SC Oncology
GA AZ0YD
UT WOS:000347966900005
PM 25410402
ER
PT J
AU Hamilton, JG
Breen, N
Klabunde, CN
Moser, RP
Leyva, B
Breslau, ES
Kobrin, SC
AF Hamilton, Jada G.
Breen, Nancy
Klabunde, Carrie N.
Moser, Richard P.
Leyva, Bryan
Breslau, Erica S.
Kobrin, Sarah C.
TI Opportunities and Challenges for the Use of Large-Scale Surveys in
Public Health Research: A Comparison of the Assessment of Cancer
Screening Behaviors
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Review
ID FORCE RECOMMENDATION STATEMENT; TRENDS SURVEY HINTS; COLORECTAL-CANCER;
CERVICAL-CANCER; INTERVIEW SURVEY; UNITED-STATES; BREAST-CANCER;
FAMILY-HISTORY; HUMAN-PAPILLOMAVIRUS; SEXUAL ORIENTATION
AB Large-scale surveys that assess cancer prevention and control behaviors are a readily available, rich resource for public health researchers. Although these data are used by a subset of researchers who are familiar with them, their potential is not fully realized by the research community for reasons including lack of awareness of the data and limited understanding of their content, methodology, and utility. Until now, no comprehensive resource existed to describe and facilitate use of these data. To address this gap and maximize use of these data, we catalogued the characteristics and content of four surveys that assessed cancer screening behaviors in 2005, the most recent year with concurrent periods of data collection: the National Health Interview Survey, Health Information National Trends Survey, Behavioral Risk Factor Surveillance System, and California Health Interview Survey. We documented each survey's characteristics, measures of cancer screening, and relevant correlates; examined how published studies (n = 78) have used the surveys' cancer screening data; and reviewed new cancer screening constructs measured in recent years. This information can guide researchers in deciding how to capitalize on the opportunities presented by these data resources. (C) 2014 AACR.
C1 [Hamilton, Jada G.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA.
[Breen, Nancy; Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA.
[Moser, Richard P.] NCI, Sci Res & Technol Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA.
[Leyva, Bryan; Breslau, Erica S.; Kobrin, Sarah C.] NCI, Proc Care Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD USA.
RP Hamilton, JG (reprint author), Mem Sloan Kettering Canc Ctr, 641 Lexington Ave,7th Floor, New York, NY 10022 USA.
EM hamiltoj@mskcc.org
FU National Cancer Institute Cancer Prevention Fellowship Program
FX G. Hamilton was supported, in part, by the National Cancer Institute
Cancer Prevention Fellowship Program.
NR 104
TC 3
Z9 3
U1 3
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2015
VL 24
IS 1
BP 3
EP 14
DI 10.1158/1055-9965.EPI-14-0568
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AZ1YG
UT WOS:000348030700001
PM 25300474
ER
PT J
AU Kim, C
Bassig, BA
Seow, WJ
Hu, W
Purdue, MP
Huang, WY
Liu, CS
Cheng, WL
Mannisto, S
Vermeulen, R
Weinstein, SJ
Lim, U
Hosgood, HD
Bonner, MR
Caporaso, NE
Albanes, D
Lan, Q
Rothman, N
AF Kim, Christopher
Bassig, Bryan A.
Seow, Wei Jie
Hu, Wei
Purdue, Mark P.
Huang, Wen-Yi
Liu, Chin-San
Cheng, Wen-Ling
Mannisto, Satu
Vermeulen, Roel
Weinstein, Stephanie J.
Lim, Unhee
Hosgood, H. Dean
Bonner, Matthew R.
Caporaso, Neil E.
Albanes, Demetrius
Lan, Qing
Rothman, Nathaniel
TI Mitochondrial DNA Copy Number and Chronic Lymphocytic Leukemia/Small
Lymphocytic Lymphoma Risk in Two Prospective Studies
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; OXIDATIVE STRESS; CANCER RISK; COHORT;
PROGRESSION; LEUKOCYTES; MARKERS; CELLS; TRIAL
AB Background: Mitochondrial DNA copy number (mtDNA CN) may be modified by mitochondria in response to oxidative stress. Previously, mtDNA CN was associated with non-Hodgkin lymphoma (NHL) risk, particularly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We conducted a replication study in the Prostate, Lung, Colorectal, and Ovarian (PLCO) study and pooled with published ATBC (Alpha-Tocopherol, Beta-Carotene) data.
Methods: In PLCO, 292 NHL cases (95 CLL/SLL cases) and 301 controls were pooled with 142 NHL cases (47 CLL/SLL cases) and 142 controls from ATBC. Subjects answered a questionnaire and provided blood. DNA was extracted from prediagnostic peripheral white blood, and mtDNA CN assayed by quantitative polymerase chain reaction. Unconditional logistic regression estimated mtDNA CN and NHL risk by odds ratios (OR) and 95% confidence intervals (95% CI).
Results: Greater mtDNA CN was associated with increased risk of CLL/SLL among males in PLCO (3rd vs. 1st tertile: OR, 2.21; 95% CI, 1.03-4.72; P-trend: 0.049) and pooled (T3 vs. T1: OR, 3.12; 95% CI, 1.72-5.68; P-trend: 0.0002). Association was stronger among male smokers (P-trend: < 0.0001) and essentially identical for cases diagnosed < 6, > 6-8, and > 8 years from blood draw (pooled: P-interaction: 0.65). mtDNA CN and risk of other NHL subtypes and multiple myeloma showed no association.
Conclusions and Impact: Mitochondrial DNA CN was associated with risk of CLL/SLL in males/male smokers. The risk was observed among cases diagnosed as long as 8 years after blood draw. These results suggest that higher mtDNA CN may reflect a process involved in CLL/SLL development. (C)2014 AACR.
C1 [Kim, Christopher; Bassig, Bryan A.; Seow, Wei Jie; Hu, Wei; Purdue, Mark P.; Huang, Wen-Yi; Weinstein, Stephanie J.; Caporaso, Neil E.; Albanes, Demetrius; Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Liu, Chin-San; Cheng, Wen-Ling] Changhua Christian Hosp, Changhua, Taiwan.
[Liu, Chin-San; Cheng, Wen-Ling] Changhua Christian Hosp, Vasc & Genom Ctr, Changhua, Taiwan.
[Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Lim, Unhee] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Hosgood, H. Dean] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY USA.
[Bonner, Matthew R.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA.
RP Kim, C (reprint author), 9609 Med Ctr Dr,MSSC 9771, Bethesda, MD 20892 USA.
EM christopher.kim@nih.gov
RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; Vermeulen,
Roel/F-8037-2011;
OI Purdue, Mark/0000-0003-1177-3108; Vermeulen, Roel/0000-0003-4082-8163;
Mannisto, Satu/0000-0002-8668-3046
FU NIH intramural research program
FX This study was supported by the NIH intramural research program.
NR 31
TC 2
Z9 2
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2015
VL 24
IS 1
BP 148
EP 153
DI 10.1158/1055-9965.EPI-14-0753
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AZ1YG
UT WOS:000348030700017
PM 25293880
ER
PT J
AU Ananthakrishnan, AN
Du, MM
Berndt, SI
Brenner, H
Caan, BJ
Casey, G
Chang-Claude, J
Duggan, D
Fuchs, CS
Gallinger, S
Giovannucci, EL
Harrison, TA
Hayes, RB
Hoffmeister, M
Hopper, JL
Hou, LF
Hsu, L
Jenkins, MA
Kraft, P
Ma, J
Nan, HM
Newcomb, PA
Ogino, S
Potter, JD
Seminara, D
Slattery, ML
Thornquist, M
White, E
Wu, KN
Peters, U
Chan, AT
AF Ananthakrishnan, Ashwin N.
Du, Mengmeng
Berndt, Sonja I.
Brenner, Hermann
Caan, Bette J.
Casey, Graham
Chang-Claude, Jenny
Duggan, David
Fuchs, Charles S.
Gallinger, Steven
Giovannucci, Edward L.
Harrison, Tabitha A.
Hayes, Richard B.
Hoffmeister, Michael
Hopper, John L.
Hou, Lifang
Hsu, Li
Jenkins, Mark A.
Kraft, Peter
Ma, Jing
Nan, Hongmei
Newcomb, Polly A.
Ogino, Shuji
Potter, John D.
Seminara, Daniela
Slattery, Martha L.
Thornquist, Mark
White, Emily
Wu, Kana
Peters, Ulrike
Chan, Andrew T.
TI Red Meat Intake, NAT2, and Risk of Colorectal Cancer: A Pooled Analysis
of 11 Studies
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENETIC SUSCEPTIBILITY; COLON-CANCER;
HETEROCYCLIC AMINES; EXCISION-REPAIR; POULTRY INTAKE; POLYMORPHISMS;
CONSUMPTION; SMOKING; COHORT
AB Background: Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported.
Methods: We used pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models.
Results: From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [ OR, 1.41; 95% confidence interval (CI), 1.29-1.55]. However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9).
Conclusion: We found that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity.
Impact: Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer. (C)2014 AACR.
C1 [Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.; Ogino, Shuji; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Du, Mengmeng; Harrison, Tabitha A.; Hsu, Li; Newcomb, Polly A.; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Berndt, Sonja I.] NCI, NIH, Bethesda, MD 20892 USA.
[Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Caan, Bette J.] German Canc Consortium, Heidelberg, Germany.
[Caan, Bette J.] Kaiser Permanente Med Care, Oakland, CA USA.
[Casey, Graham] Univ So Calif, Los Angeles, CA USA.
[Chang-Claude, Jenny] German Canc Res Ctr DFKZ, Div Canc Epidemiol, Heidelberg, Germany.
[Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA.
[Fuchs, Charles S.; Ma, Jing] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fuchs, Charles S.; Giovannucci, Edward L.; Ma, Jing; Ogino, Shuji; Wu, Kana] Channing Div Network Med, Boston, MA USA.
[Gallinger, Steven] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Hayes, Richard B.] NYU, Sch Med, New York, NY USA.
[Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat Hlth, Melbourne, Vic, Australia.
[Hou, Lifang] Northwestern Univ, Dept Prevent Med, Evanston, IL USA.
[Hou, Lifang] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Evanston, IL USA.
[Nan, Hongmei] Indiana Univ, Simon Canc Ctr, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Potter, John D.; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Slattery, Martha L.] Univ Utah Hlth Sci, Salt Lake City, UT USA.
RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
EM upeters@fhcrc.org; achan@mgh.harvard.edu
RI Hoffmeister, Michael/B-5745-2012; Jenkins, Mark/P-7803-2015; Gallinger,
Steven/E-4575-2013; Brenner, Hermann/B-4627-2017;
OI Hoffmeister, Michael/0000-0002-8307-3197; Jenkins,
Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572; Potter,
John/0000-0001-5439-1500; Hayes, Richard/0000-0002-0918-661X
FU NIH [K23 DK097142, UM1 CA167551, U01 CA122839, R01 CA143237, R01
CA48998, P01 CA 055075, UM1 CA167552, R01 CA137178, R01 CA151993, P01 CA
087969, P50 CA 127003, R01 CA042182, U01 HG004446, K05 CA154337]; GECCO;
NCI; U.S. Department of Health and Human Services [U01 CA137088, R01
CA059045, R25 CA094880]; Australasian Colorectal Cancer Family Registry
[U01/U24 CA097735]; Ontario Registry for Studies of Familial Colorectal
Cancer [U01/U24 CA074783]; Seattle Colorectal Cancer Family Registry
[U01/U24 CA074794]; German Research Council (Deutsche
Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH
117/1-1]; German Federal Ministry of Education and Research [01KH0404,
01ER0814]; NIH through Ontario Registry for Studies of Familial
Colorectal Cancer [U01 CA074783]; Ontario Research Fund [GL2]; Canadian
Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program
grant from the Canadian Cancer Society Research Institute; Intramural
Research Program of the Division of Cancer Epidemiology and Genetics
and; Division of Cancer Prevention, NCI, NIH, DHHS; NIH, Genes,
Environment and Health Initiative (GEI) [Z01 CP 010200]; NIH GEI [U01 HG
004438]; National Heart, Lung, and Blood Institute, National Institutes
of Health, U.S. Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
FX A. Ananthakrishnan is supported by a grant from the NIH (K23 DK097142).
M. Du, T. A Harrison, L. Hsu, M. Thornquist, and U. Peters are
affiliated with GECCO, which is supported by the following grants from
the NCI, NIH and U.S. Department of Health and Human Services (U01
CA137088, R01 CA059045, R25 CA094880; to M. Du).; G. Casey, J.L. Hopper,
M.A. Jenkins, and P.A. Newcomb are affiliated with CCFR, which is
supported by the NIH (UM1 CA167551) and through cooperative agreements
with members of the Colon Cancer Family Registry and Principal
Investigators. This genome-wide scan was supported by the NCI, NIH by
U01 CA122839 and R01 CA143237 (to G. Casey). The following Colon CFR
centers contributed data to this article and were supported by the NIH:;
Australasian Colorectal Cancer Family Registry (U01/U24 CA097735),
Ontario Registry for Studies of Familial Colorectal Cancer (U01/U24
CA074783). Seattle Colorectal Cancer Family Registry (U01/U24
CA074794).; H. Brenner, J. Chang-Claude, and M. Hoffmeister are
affiliated with DACHS, which was supported by grants from the German
Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR
1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry
of Education and Research (01KH0404 and 01ER0814).; J.D. Potter and M.L.
Slattery are affiliated with DALS, which was supported by the NIH (R01
CA48998; to M.L. Slattery).; A.T. Chan, C.S. Fuchs, K. Wu, E.L.
Giovannucci, J. Ma, and S. Ogino are affiliated with HPFS, NHS, and PHS,
which are supported by the NIH. HPFS is supported by the NIH (P01 CA
055075, UM1 CA167552, R01 CA137178, R01 CA151993, and P50 CA 127003),
NHS by the NIH (R01 CA137178, R01 CA151993, P01 CA 087969, and P50 CA
127003) and PHS by the NIH (R01 CA042182).; S. Gallinger is affiliated
with theOFCCR, which is supported by funding from the NIH through
funding allocated to the Ontario Registry for Studies of Familial
Colorectal Cancer (U01 CA074783); see CCFR section above. As subset of
ARCTIC, OFCCR is supported by a GL2 grant from the Ontario Research
Fund, the Canadian Institutes of Health Research, and the Cancer Risk
Evaluation (CaRE) Program grant from the Canadian Cancer Society
Research Institute.; S.I. Berndt and R.B. Hayes are affiliated with the
PLCO, which is supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and supported by contracts
from the Division of Cancer Prevention, NCI, NIH, DHHS. In addition, a
subset of control samples were genotyped as part of the Cancer Genetic
Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager and
colleagues Nat Genet 2007; 39: 645-9), Colon CGEMS pancreatic cancer
scan (PanScan; Amundadottir and colleagues Nat Genet 2009; 41: 986-90
and Petersen and colleagues Nat Genet 2010; 42: 224-8), and the Lung
Cancer and Smoking study. The prostate and PanScan study datasets were
accessed with appropriate approval through the dbGaP online resource
(http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and
phs000206. v3. p2, respectively, and the lung datasets were accessed
from the dbGaP website (http://www. ncbi. nlm. nih. gov/gap) through
accession number phs000093.v2.p2. Funding for the Lung Cancer and
Smoking study was provided by NIH, Genes, Environment and Health
Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG
004438. For the lung study, the GENEVA Coordinating Center provided
assistance with genotype cleaning and general study coordination, and
the Johns Hopkins University Center for Inherited Disease Research
conducted genotyping.; P. A. Newcomb is affiliated with PMH, which is
supported by the NIH (R01 CA076366; to P. A. Newcomb).; E. White is
affiliated with VITAL, which is supported by the NIH (K05 CA154337).; D.
Duggan is affiliated with TGEN and funded through a subaward with GECCO
(R01 CA059045).; The WHI program is funded by the National Heart, Lung,
and Blood Institute, National Institutes of Health, U.S. Department of
Health and Human Services through contracts HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, and HHSN271201100004C.
NR 51
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Z9 6
U1 2
U2 20
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2015
VL 24
IS 1
BP 198
EP 205
DI 10.1158/1055-9965.EPI-14-0897
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AZ1YG
UT WOS:000348030700023
PM 25342387
ER
PT J
AU Loeb, S
Peskoe, SB
Joshu, CE
Huang, WY
Hayes, RB
Carter, HB
Isaacs, WB
Platz, EA
AF Loeb, Stacy
Peskoe, Sarah B.
Joshu, Corinne E.
Huang, Wen-Yi
Hayes, Richard B.
Carter, H. Ballentine
Isaacs, William B.
Platz, Elizabeth A.
TI Do Environmental Factors Modify the Genetic Risk of Prostate Cancer?
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GENOME-WIDE ASSOCIATION; SELENIUM
SUPPLEMENTATION; SEQUENCE VARIANTS; TRIAL; PREVENTION; LOCI;
SUSCEPTIBILITY; ANTIGEN; VEGETABLES
AB Background: Many SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown.
Methods: We evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (>= 12 SNPs) and prostate cancer within environmental factor strata and tested for interaction.
Results: Men with >= 12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for >= 12 alleles was 2.06 [95% confidence interval (CI), 1.67-2.55] in nonusers and 0.99 (0.38-2.58) in users (P-interaction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with < 12 alleles and nonusers, the OR for >= 12 alleles was 2.25 (1.69-3.00) in nonusers and 1.70 (1.25-2.32) in users (P-interaction = 0.009). This pattern was similar for ibuprofen (P-interaction = 0.023) and vegetables (P-interaction = 0.010).
Conclusions: This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer.
Impact: The effect of genetic factors on prostate cancer risk may vary by lifestyle interventions. (C)2014 AACR.
C1 [Loeb, Stacy] NYU, Dept Urol, New York, NY 10016 USA.
[Loeb, Stacy; Hayes, Richard B.] NYU, New York, NY 10016 USA.
[Peskoe, Sarah B.; Joshu, Corinne E.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Huang, Wen-Yi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Carter, H. Ballentine; Isaacs, William B.; Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Carter, H. Ballentine; Isaacs, William B.; Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
RP Loeb, S (reprint author), NYU, 550 1st Ave,VZ30 6th Floor 612, New York, NY 10016 USA.
EM stacyloeb@gmail.com
FU National Cancer Institute, NIH, Department of Health and Human Services
[P50 CA58236, K07 CA178258]; Louis Feil Charitable Lead Trust
FX This work was supported by P50 CA58236 (to W.G. Nelson) from the
National Cancer Institute, NIH, Department of Health and Human Services,
and by K07 CA178258 from the National Cancer Institute, NIH, Department
of Health and Human Services (to S. Loeb). This work was also supported
by the Louis Feil Charitable Lead Trust to S. Loeb.
NR 34
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U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2015
VL 24
IS 1
BP 213
EP 220
DI 10.1158/1055-9965.EPI-14-0786-T
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AZ1YG
UT WOS:000348030700025
PM 25342390
ER
PT J
AU Trabert, B
Wentzensen, N
Felix, AS
Yang, HP
Sherman, ME
Brinton, LA
AF Trabert, Britton
Wentzensen, Nicolas
Felix, Ashley S.
Yang, Hannah P.
Sherman, Mark E.
Brinton, Louise A.
TI Metabolic Syndrome and Risk of Endometrial Cancer in the United States:
A Study in the SEER-Medicare Linked Database
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BODY-SIZE; CARCINOMA; ABNORMALITIES; HYPERTENSION; OVERWEIGHT; HEALTH;
ADULTS; WOMEN; LIFE; MASS
AB Background: Metabolic syndrome and its component feature, central obesity, are associated with endometrial cancer risk. It remains unclear whether associations with the other metabolic factors that comprise metabolic syndrome are independent of the obesity-endometrial cancer association. Furthermore, the link with specific endometrial cancer subtypes remains ill-defined, despite evidence of etiologic heterogeneity among these tumors.
Methods: In a case-control study within the SEER-Medicare linked database, we examined whether metabolic factors, individually or combined, were associated with endometrial cancer. Cases (n = 16,323) were women diagnosed with endometrial cancer from 1993 through 2007. Controls (n = 100,751) were a 5% sample of female Medicare enrollees residing in the same SEER registry area as cases. Metabolic syndrome was defined using ICD-9-CM codes from inpatient/outpatient diagnoses 1 to 3 years before case diagnosis and a comparable time period in controls. ORs and 95% confidence intervals (CI) were estimated using logistic regression.
Results: Endometrial cancer risk was associated with metabolic syndrome [OR (95% CI): 1.39 (1.32-1.47)] and its component factors: overweight/obesity [1.95 (1.80-2.11)], impaired fasting glucose [1.36 (1.30-1.43)], high blood pressure [1.31 (1.25-1.36)], and high triglycerides [1.13 (1.08-1.18)]. After adjusting for overweight/obesity, the increased risks associated with the metabolic syndrome factors remained. Heterogeneity of associations by subtype were not identified (P-heterogeneity - 0.82).
Conclusions: Among women age 65 and older in the United States, metabolic syndrome, and its component factors, increased endometrial cancer risk similarly across endometrial cancer subtypes.
Impact: Strategies to reduce the prevalence of metabolic syndrome factors might have a favorable effect on endometrial cancer incidence.(C) 2015 AACR.
C1 [Trabert, Britton; Wentzensen, Nicolas; Felix, Ashley S.; Yang, Hannah P.; Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Trabert, B (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM britton.trabert@nih.gov
RI Brinton, Louise/G-7486-2015; Trabert, Britton/F-8051-2015; Felix,
Ashley/A-3240-2016
OI Brinton, Louise/0000-0003-3853-8562;
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This research was supported by Intramural Research Program of the
National Cancer Institute, National Institutes of Health.
NR 30
TC 18
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U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2015
VL 24
IS 1
BP 261
EP 267
DI 10.1158/1055-9965.EPI-14-0923
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AZ1YG
UT WOS:000348030700031
PM 25587111
ER
PT J
AU Peterlongo, P
Chang-Claude, J
Moysich, KB
Rudolph, A
Schmutzler, RK
Simard, J
Soucy, P
Eeles, RA
Easton, DF
Hamann, U
Wilkening, S
Chen, BW
Rookus, MA
Schmidt, M
van der Baan, FH
Spurdle, AB
Walker, LC
Lose, F
Maia, AT
Montagna, M
Matricardi, L
Lubinski, J
Jakubowska, A
Garcia, EBG
Olopade, OI
Nussbaum, RL
Nathanson, KL
Domchek, SM
Rebbeck, TR
Arun, BK
Karlan, BY
Orsulic, S
Lester, J
Chung, WK
Miron, A
Southey, MC
Goldgar, DE
Buys, SS
Janavicius, R
Dorfling, CM
van Rensburg, EJ
Ding, YC
Neuhausen, SL
Hansen, TVO
Gerdes, AM
Ejlertsen, B
Jonson, L
Osorio, A
Martinez-Bouzas, C
Benitez, J
Conway, EE
Blazer, KR
Weitzel, JN
Manoukian, S
Peissel, B
Zaffaroni, D
Scuvera, G
Barile, M
Ficarazzi, F
Mariette, F
Fortuzzi, S
Viel, A
Giannini, G
Papi, L
Martayan, A
Tibiletti, MG
Radice, P
Vratimos, A
Fostira, F
Garber, JE
Donaldson, A
Brewer, C
Foo, C
Evans, DGR
Frost, D
Eccles, D
Brady, A
Cook, J
Tischkowitz, M
Adlard, J
Barwell, J
Walker, L
Izatt, L
Side, LE
Kennedy, MJ
Rogers, MT
Porteous, ME
Morrison, PJ
Platte, R
Davidson, R
Hodgson, SV
Ellis, S
Cole, T
Godwin, AK
Claes, K
Van Maerken, T
Meindl, A
Gehrig, A
Sutter, C
Engel, C
Niederacher, D
Steinemann, D
Plendl, H
Kast, K
Rhiem, K
Ditsch, N
Arnold, N
Varon-Mateeva, R
Wappenschmidt, B
Wang-Gohrke, S
Bressac-de Paillerets, B
Buecher, B
Delnatte, C
Houdayer, C
Stoppa-Lyonnet, D
Damiola, F
Coupier, I
Barjhoux, L
Venat-Bouvet, L
Golmard, L
Boutry-Kryza, N
Sinilnikova, OM
Caron, O
Pujol, P
Mazoyer, S
Belotti, M
Piedmonte, M
Friedlander, ML
Rodriguez, GC
Copeland, LJ
de la Hoya, M
Segura, PP
Nevanlinna, H
Aittomaki, K
van Os, TAM
Meijers-Heijboer, HEJ
van der Hout, AH
Vreeswijk, MPG
Hoogerbrugge, N
Ausems, MGEM
van Doorn, HC
Collee, JM
Olah, E
Diez, O
Blanco, I
Lazaro, C
Brunet, J
Feliubadalo, L
Cybulski, C
Gronwald, J
Durda, K
Jaworska-Bieniek, K
Sukiennicki, G
Arason, A
Chiquette, J
Teixeira, MR
Olswold, C
Couch, FJ
Lindor, NM
Wang, XS
Szabo, CI
Offit, K
Corines, M
Jacobs, L
Robson, ME
Zhang, LY
Joseph, V
Berger, A
Singer, CF
Rappaport, C
Kaulich, DG
Pfeiler, G
Tea, MKM
Phelan, CM
Greene, MH
Mai, PL
Rennert, G
Mulligan, AM
Glendon, G
Tchatchou, S
Andrulis, IL
Toland, AE
Bojesen, A
Pedersen, IS
Thomassen, M
Jensen, UB
Laitman, Y
Rantala, J
von Wachenfeldt, A
Ehrencrona, H
Askmalm, MS
Borg, A
Kuchenbaecker, KB
McGuffog, L
Barrowdale, D
Healey, S
Lee, A
Pharoah, PDP
Chenevix-Trench, G
Antoniou, AC
Friedman, E
AF Peterlongo, Paolo
Chang-Claude, Jenny
Moysich, Kirsten B.
Rudolph, Anja
Schmutzler, Rita K.
Simard, Jacques
Soucy, Penny
Eeles, Rosalind A.
Easton, Douglas F.
Hamann, Ute
Wilkening, Stefan
Chen, Bowang
Rookus, Matti A.
Schmidt, MarjankaK.
van der Baan, Frederieke H.
Spurdle, Amanda B.
Walker, Logan C.
Lose, Felicity
Maia, Ana-Teresa
Montagna, Marco
Matricardi, Laura
Lubinski, Jan
Jakubowska, Anna
Garcia, Encarna B. Gomez
Olopade, Olufunmilayo I.
Nussbaum, Robert L.
Nathanson, Katherine L.
Domchek, Susan M.
Rebbeck, Timothy R.
Arun, Banu K.
Karlan, Beth Y.
Orsulic, Sandra
Lester, Jenny
Chung, Wendy K.
Miron, Alex
Southey, Melissa C.
Goldgar, David E.
Buys, Saundra S.
Janavicius, Ramunas
Dorfling, Cecilia M.
van Rensburg, Elizabeth J.
Ding, Yuan Chun
Neuhausen, Susan L.
Hansen, Thomas V. O.
Gerdes, Anne-Marie
Ejlertsen, Bent
Jonson, Lars
Osorio, Ana
Martinez-Bouzas, Cristina
Benitez, Javier
Conway, Edye E.
Blazer, Kathleen R.
Weitzel, Jeffrey N.
Manoukian, Siranoush
Peissel, Bernard
Zaffaroni, Daniela
Scuvera, Giulietta
Barile, Monica
Ficarazzi, Filomena
Mariette, Frederique
Fortuzzi, Stefano
Viel, Alessandra
Giannini, Giuseppe
Papi, Laura
Martayan, Aline
Tibiletti, Maria Grazia
Radice, Paolo
Vratimos, Athanassios
Fostira, Florentia
Garber, Judy E.
Donaldson, Alan
Brewer, Carole
Foo, Claire
Evans, D. Gareth R.
Frost, Debra
Eccles, Diana
Brady, Angela
Cook, Jackie
Tischkowitz, Marc
Adlard, Julian
Barwell, Julian
Walker, Lisa
Izatt, Louise
Side, Lucy E.
Kennedy, M. John
Rogers, Mark T.
Porteous, Mary E.
Morrison, Patrick J.
Platte, Radka
Davidson, Rosemarie
Hodgson, Shirley V.
Ellis, Steve
Cole, Trevor
Godwin, Andrew K.
Claes, Kathleen
Van Maerken, Tom
Meindl, Alfons
Gehrig, Andrea
Sutter, Christian
Engel, Christoph
Niederacher, Dieter
Steinemann, Doris
Plendl, Hansjoerg
Kast, Karin
Rhiem, Kerstin
Ditsch, Nina
Arnold, Norbert
Varon-Mateeva, Raymonda
Wappenschmidt, Barbara
Wang-Gohrke, Shan
Bressac-de Paillerets, Brigitte
Buecher, Bruno
Delnatte, Capucine
Houdayer, Claude
Stoppa-Lyonnet, Dominique
Damiola, Francesca
Coupier, Isabelle
Barjhoux, Laure
Venat-Bouvet, Laurence
Golmard, Lisa
Boutry-Kryza, Nadia
Sinilnikova, Olga M.
Caron, Olivier
Pujol, Pascal
Mazoyer, Sylvie
Belotti, Muriel
Piedmonte, Marion
Friedlander, Michael L.
Rodriguez, Gustavo C.
Copeland, Larry J.
de la Hoya, Miguel
Perez Segura, Pedro
Nevanlinna, Heli
Aittomaeki, Kristiina
van Os, Theo A. M.
Meijers-Heijboer, Hanne E. J.
van der Hout, Annemarie H.
Vreeswijk, Maaike P. G.
Hoogerbrugge, Nicoline
Ausems, Margreet G. E. M.
van Doorn, Helena C.
Collee, J. Margriet
Olah, Edith
Diez, Orland
Blanco, Ignacio
Lazaro, Conxi
Brunet, Joan
Feliubadalo, Lidia
Cybulski, Cezary
Gronwald, Jacek
Durda, Katarzyna
Jaworska-Bieniek, Katarzyna
Sukiennicki, Grzegorz
Arason, Adalgeir
Chiquette, Jocelyne
Teixeira, Manuel R.
Olswold, Curtis
Couch, Fergus J.
Lindor, Noralane M.
Wang, Xianshu
Szabo, Csilla I.
Offit, Kenneth
Corines, Marina
Jacobs, Lauren
Robson, Mark E.
Zhang, Liying
Joseph, Vijai
Berger, Andreas
Singer, Christian F.
Rappaport, Christine
Kaulich, Daphne Geschwantler
Pfeiler, Georg
Tea, Muy-Kheng M.
Phelan, Catherine M.
Greene, Mark H.
Mai, Phuong L.
Rennert, Gad
Mulligan, Anna Marie
Glendon, Gord
Tchatchou, Sandrine
Andrulis, Irene L.
Toland, Amanda Ewart
Bojesen, Anders
Pedersen, Inge Sokilde
Thomassen, Mads
Jensen, Uffe Birk
Laitman, Yael
Rantala, Johanna
von Wachenfeldt, Anna
Ehrencrona, Hans
Askmalm, Marie Stenmark
Borg, Ake
Kuchenbaecker, Karoline B.
McGuffog, Lesley
Barrowdale, Daniel
Healey, Sue
Lee, Andrew
Pharoah, Paul D. P.
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Friedman, Eitan
CA EMBRACE
GEMO Study Collaborators
HEBON
KConFab Investigators
TI Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1
and BRCA2 Mutation Carriers
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ASSOCIATION
AB Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.
Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.
Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.
Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.
Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. (C)2014 AACR.
C1 [Peterlongo, Paolo; Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano] Fdn Ist FIRC Oncol Molecolare, IFOM, I-20139 Milan, Italy.
[Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Cancer Epidemiol, Heidelberg, Germany.
[Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Schmutzler, Rita K.; Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.; Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Hosp Cologne, Fac Med, Ctr Integrated Oncol, Cologne, Germany.
[Schmutzler, Rita K.] Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany.
[Simard, Jacques; Soucy, Penny] Ctr Hosp Univ Quebec Res Ctr, Quebec City, PQ, Canada.
[Simard, Jacques; Soucy, Penny] Univ Laval, Quebec City, PQ, Canada.
[Eeles, Rosalind A.] Inst Canc Res, Oncogenet Team, Surrey, England.
[Eeles, Rosalind A.] Royal Marsden NHS Fdn Trust, Surrey, England.
[Easton, Douglas F.; Frost, Debra; Platte, Radka; Ellis, Steve; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Antoniou, Antonis C.; EMBRACE] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Hamann, Ute; Wilkening, Stefan; Chen, Bowang] German Canc Res Ctr, Heidelberg, Germany.
[Rookus, Matti A.; van der Baan, Frederieke H.; HEBON] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Schmidt, MarjankaK.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands.
[Spurdle, Amanda B.; Lose, Felicity; Healey, Sue; Chenevix-Trench, Georgia] QIMR Berghofer, Dept Genet & Computat Biol, Brisbane, Qld, Australia.
[Walker, Logan C.] Univ Otago, Dept Pathol, Christchurch, New Zealand.
[Maia, Ana-Teresa] Univ Algarve, Dept Biomed Sci & Med, Algarve, Portugal.
[Montagna, Marco; Matricardi, Laura] IRCCS, Ist Oncol Veneto, Immunol & Mol Oncol Unit, Padua, Italy.
[Lubinski, Jan; Jakubowska, Anna; Cybulski, Cezary; Gronwald, Jacek; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Sukiennicki, Grzegorz] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Garcia, Encarna B. Gomez] MUMC, Dept Clin Genet, Maastricht, Netherlands.
[Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Dept Med & Human Genet, Ctr Clin Canc Genet, Chicago, IL 60637 USA.
[Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Nussbaum, Robert L.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Dept Epidemiol & Biostat, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Karlan, Beth Y.; Orsulic, Sandra; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Chung, Wendy K.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
[Chung, Wendy K.] Columbia Univ, Dept Med, New York, NY USA.
[Miron, Alex] Case Western Reserve Med Sch, Dept Genet & Genom, Cleveland, OH USA.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
[Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA.
[Buys, Saundra S.] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA.
[Janavicius, Ramunas] Vilnius Univ Hosp Santariskiu Clin, Hematol Oncol & Transfus Med Ctr, Dept Mol & Regenerat Med, Vilnius, Lithuania.
[Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Vilnius, Lithuania.
[Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa.
[Ding, Yuan Chun; Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA.
[Hansen, Thomas V. O.; Jonson, Lars] Univ Copenhagen Hosp, Rigshosp, Ctr Genom Med, DK-2100 Copenhagen, Denmark.
[Gerdes, Anne-Marie] Univ Copenhagen Hosp, Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
[Ejlertsen, Bent] Univ Copenhagen Hosp, Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark.
[Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain.
[Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain.
[Martinez-Bouzas, Cristina] Cruces Hosp Barakaldo, Dept Biochem, Mol Genet Lab, Barakaldo Bizkaia 48903, Spain.
[Benitez, Javier] Spanish Natl Canc Ctr CNIO, Genotyping Unit, Madrid, Spain.
[Conway, Edye E.] City Hope Clin Canc Genet Community Res Network, St Alphonsus Reg Med Ctr, Duarte, CA USA.
[Blazer, Kathleen R.] City Hope Natl Med Ctr, Duarte, CA USA.
[Weitzel, Jeffrey N.] City Hope Clin Canc Genet Community Res Network, City Hope, Duarte, CA USA.
[Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predictive Med, Unit Med Genet, Milan, Italy.
[Barile, Monica] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Ficarazzi, Filomena; Mariette, Frederique; Fortuzzi, Stefano] Cogentech Canc Genet Test Lab, Milan, Italy.
[Viel, Alessandra] CRO Aviano Natl Canc Inst, Div Expt Oncol 1, Aviano, PN, Italy.
[Giannini, Giuseppe] Univ Roma La Sapienza, Dept Mol Med, I-00185 Rome, Italy.
[Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy.
[Martayan, Aline] Ist Nazl Tumori Regina Elena, Dept Med Oncol, Unit Genet Counseling, Rome, Italy.
[Tibiletti, Maria Grazia] Polo Univ Varese, UO Anat Patolog Osped Circolo & Fdn Macchi, Varese, Italy.
[Vratimos, Athanassios; Fostira, Florentia] Natl Ctr Sci Res Demokritos, INRASTES, Mol Diagnost Lab, Athens, Greece.
[Garber, Judy E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England.
[Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England.
[Foo, Claire] Liverpool Womens NHS Fdn Trust, Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England.
[Evans, D. Gareth R.] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Eccles, Diana] Univ Southampton, Fac Med, Southampton Univ Hosp NHS Trust, Southampton SO9 5NH, Hants, England.
[Brady, Angela] Kennedy Galton Ctr, North West Thames Reg Genet Serv, Harrow, Middx, England.
[Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England.
[Tischkowitz, Marc] Addenbrookes Hosp, East Anglian Reg Genet Serv, Dept Clin Genet, Cambridge, England.
[Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England.
[Barwell, Julian] Univ Hosp Leicester NHS Trust, Leicestershire Clin Genet Serv, Leicester, Leics, England.
[Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England.
[Izatt, Louise] Guys & St Thomas NHS Fdn Trust, London, England.
[Side, Lucy E.] Great Ormond St Hosp Sick Children, North East Thames Reg Genet Serv, London WC1N 3JH, England.
[Kennedy, M. John] Univ Dublin Trinity Coll, Acad Unit Clin & Mol Oncol, Dublin 2, Ireland.
[Kennedy, M. John] St James Hosp, Dublin 8, Ireland.
[Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales.
[Porteous, Mary E.] Western Gen Hosp, South East Scotland Reg Genet Serv, Edinburgh EH4 2XU, Midlothian, Scotland.
[Morrison, Patrick J.] Queens Univ Belfast, Dept Med Genet, Belfast HSC Trust, Ctr Canc Res & Cell Biol, Belfast, Antrim, North Ireland.
[Davidson, Rosemarie] So Gen Hosp, West Scotland Reg Genet Serv, Glasgow G51 4TF, Lanark, Scotland.
[Hodgson, Shirley V.] St Georges Univ London, Med Genet Unit, London, England.
[Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, MO USA.
[Claes, Kathleen; Van Maerken, Tom] Univ Ghent, Ctr Genet Med, B-9000 Ghent, Belgium.
[Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Gynecol & Obstet, D-80290 Munich, Germany.
[Gehrig, Andrea] Univ Wurzburg, Inst Human Genet, Wurzburg, Germany.
[Sutter, Christian] Heidelberg Univ, Heidelberg, Germany.
[Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Dusseldorf, Germany.
[Steinemann, Doris] Hannover Med Sch, Hannover, NH, Germany.
[Plendl, Hansjoerg] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein, Kiel, Germany.
[Kast, Karin] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Gynecol & Obstet, Dresden, Germany.
[Rhiem, Kerstin; Wappenschmidt, Barbara] Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany.
[Ditsch, Nina] Univ Munich, Dept Gynecol & Obstet, Munich, Germany.
[Arnold, Norbert] Univ Kiel, Dept Gynecol & Obstet, Univ Hosp Schleswig Holstein, Kiel, Germany.
[Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Berlin, Germany.
[Wang-Gohrke, Shan] Univ Hosp Ulm, Dept Gynecol & Obstet, Ulm, Germany.
[Bressac-de Paillerets, Brigitte] Fdn Jean Dausset, INSERM U946, Paris, France.
[Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Villejuif, France.
[Buecher, Bruno; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Golmard, Lisa; Belotti, Muriel] Inst Curie, Dept Tumour Biol, Paris, France.
[Delnatte, Capucine] Ctr Rene Gauducheau, F-44035 Nantes, France.
[Houdayer, Claude; Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Stoppa-Lyonnet, Dominique] INSERM U830, Inst Curie, Paris, France.
[Damiola, Francesca; Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon 1, Ctr Rech Cancerol Lyon, INSERM U1052, CNRS UMR5286, F-69365 Lyon, France.
[Coupier, Isabelle; Pujol, Pascal] CHU Arnaud Villeneuve, Unit Oncogenet, Montpellier, France.
[Coupier, Isabelle; Barjhoux, Laure] CRLCC Val Aurelle, Unit Oncogenet, Montpellier, France.
[Venat-Bouvet, Laurence] Ctr Hosp Univ Dupuytren, Dept Med Oncol, Limoges, France.
[Boutry-Kryza, Nadia; Sinilnikova, Olga M.] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitutionnelle Canc Frequent, Lyon, France.
[Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France.
[Pujol, Pascal] INSERM 896, CRCM Val Aurelle, Montpellier, France.
[GEMO Study Collaborators] GEMO Study Natl Canc Genet Network, UNICANCER Genet Grp, Paris, France.
[Piedmonte, Marion] Roswell Pk Canc Inst, Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY 14263 USA.
[Friedlander, Michael L.] Australia New Zealand Gynaecol Oncol Grp, Coordinating Ctr, Camperdown, NSW, Australia.
[Rodriguez, Gustavo C.] NorthShore Univ HealthSyst, Div Gynecol Oncol, Evanston, IL USA.
[Copeland, Larry J.] Ohio State Univ, Dept Obstet & Gynecol, Hilliard, OH USA.
[de la Hoya, Miguel] Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, Madrid, Spain.
[Perez Segura, Pedro] Hosp Clin San Carlos, IdISSC, Dept Oncol, Madrid, Spain.
[Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Nevanlinna, Heli] Univ Helsinki, Helsinki, Finland.
[Aittomaeki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland.
[van Os, Theo A. M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands.
[van der Hout, Annemarie H.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Vreeswijk, Maaike P. G.] Leiden Univ, Med Ctr LUMC, Dept Human Genet, Leiden, Netherlands.
[Hoogerbrugge, Nicoline] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
[Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[van Doorn, Helena C.] Erasmus Univ, Dept Obstet & Ginecol, Div Gynecol Oncol, MC Canc Inst, Rotterdam, Netherlands.
[Collee, J. Margriet] Erasmus Univ, Med Ctr, Dept Clin Genet, Family Canc Clin, Rotterdam, Netherlands.
[Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Diez, Orland] Univ Hosp Vall Hebron, Oncol Grp, Barcelona, Spain.
[Diez, Orland] Univ Autonoma Barcelona, E-08193 Barcelona, Spain.
[Diez, Orland] Vall Hebron Inst Oncol, Barcelona, Spain.
[Diez, Orland] Vall Hebron Res Inst, Barcelona, Spain.
[Blanco, Ignacio] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Barcelona, Spain.
[Lazaro, Conxi] IDIBELL Catalan Inst Oncol, Hereditary Canc Program, Mol Diagnost Unit, Barcelona, Spain.
[Brunet, Joan] IDIBGI Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain.
[Feliubadalo, Lidia; Arason, Adalgeir] Univ Iceland, Fac Med, BMC, Reykjavik, Iceland.
[Arason, Adalgeir] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Chiquette, Jocelyne] Univ Quebec, Ctr Rech FRSQ Ctr Hosp Affilie, Ctr Malad Sein Deschenes Fabia, Unite Rech Sante Populat, Quebec City, PQ, Canada.
[Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4100 Oporto, Portugal.
[Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal.
[Olswold, Curtis] Mayo Clin, Dept Hlth Sci Res, Rochester, NY USA.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol & Hlth Sci Res, Rochester, NY USA.
[Lindor, Noralane M.] Mayo Clin, Scottsdale, AZ USA.
[Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, NY USA.
[Szabo, Csilla I.] NIH, NHGRI, Bethesda, MD 20892 USA.
[Offit, Kenneth; Robson, Mark E.; Joseph, Vijai] Mem Sloan Kettering Canc Ctr, Clin Genet Res Lab, New York, NY 10021 USA.
[Corines, Marina; Jacobs, Lauren] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA.
[Zhang, Liying] Mem Sloan Kettering Canc Ctr, Dept Pathol, Diagnost Mol Genet Lab, New York, NY 10021 USA.
[Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.] Med Univ Vienna, Dept OB GYN, Vienna, Austria.
[Berger, Andreas; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng M.] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria.
[Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA.
[Greene, Mark H.; Mai, Phuong L.] NIH, Natl Canc Inst, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD USA.
[Rennert, Gad] Clalit Natl Canc Control Ctr, Haifa, Israel.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
[Tchatchou, Sandrine; Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Ohio State Univ, Ctr Comprehens Canc, Dept Med Genet, Columbus, OH 43210 USA.
[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol, Columbus, OH 43210 USA.
[Toland, Amanda Ewart] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med & Mol Virol, Div Human Canc Genet, Columbus, OH 43210 USA.
[Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
[Pedersen, Inge Sokilde] Aalborg Univ Hosp, Dept Biochem, Sect Mol Diagnost, Aalborg, Denmark.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark.
[Laitman, Yael] Sheba Med Ctr, Tel Aviv, Israel.
[Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
[von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden.
[Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden.
[Ehrencrona, Hans] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Askmalm, Marie Stenmark] Linkoping Univ, Dept Clin & Expt Med, Div Clin Genet, Linkoping, Sweden.
[Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden.
[Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England.
[KConFab Investigators] kConFab Kathleen Cuningham Consortium Res Familia, Peter Mac Callum Canc Ctr, Melbourne, Vic, Australia.
RP Peterlongo, P (reprint author), Fdn Ist FIRC Oncol Molecolare, IFOM, Via Adamello 16, I-20139 Milan, Italy.
EM paolo.peterlongo@ifom.eu; eitan.friedman@sheba.health.gov.il
RI Spurdle, Amanda/A-4978-2011; Feliubadalo, Lidia/G-4577-2016; Andrulis,
Irene/E-7267-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011;
Giannini, Giuseppe/B-5672-2013; montagna, marco/E-2225-2012;
Hoogerbrugge, Nicoline/O-1016-2013; Osorio, Ana/I-4324-2014; Maia,
Ana-Teresa/F-4404-2012; Teixeira, Manuel/E-4885-2011; Gronwald,
Jacek/A-4576-2017; manoukian, siranoush/E-7132-2017; Peissel,
Bernard/E-8187-2017;
OI Brunet, Joan/0000-0003-1945-3512; Joseph, Vijai/0000-0002-7933-151X;
VENAT-BOUVET, Laurence/0000-0002-0716-2550; Evans,
Gareth/0000-0002-8482-5784; Papi, Laura/0000-0003-4552-9517; Robson,
Mark/0000-0002-3109-1692; Barrowdale, Daniel/0000-0003-1661-3939; Lose,
Felicity/0000-0001-8337-3547; Nevanlinna, Heli/0000-0002-0916-2976;
Eeles, Rosalind/0000-0002-3698-6241; Blanco,
Ignacio/0000-0002-7414-7481; Spurdle, Amanda/0000-0003-1337-7897;
Feliubadalo, Lidia/0000-0002-1736-0112; Ehrencrona,
Hans/0000-0002-5589-3622; Rappaport-Fuerhauser,
Christine/0000-0002-6820-0020; Giannini, Giuseppe/0000-0003-0299-4056;
montagna, marco/0000-0002-4929-2150; Osorio, Ana/0000-0001-8124-3984;
Maia, Ana-Teresa/0000-0002-0454-9207; Teixeira,
Manuel/0000-0002-4896-5982; Gronwald, Jacek/0000-0002-3643-2871;
manoukian, siranoush/0000-0002-6034-7562; Peissel,
Bernard/0000-0001-9233-3571; Fortuzzi, Stefano/0000-0002-5662-3800
FU European Community (COGS) [223175, HEALTH-F2-2009-223175]; Cancer
Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014,
C5047/A8384, C5047/ A15007, C5047/A10692, C1287/A16563, C1287/A17523,
C5047/A8385]; NIH [CA128978, R01-CA102776, R01CA083855]; Post-Cancer
GWAS initiative [1U19CA148537, 1U19 CA148065, 1U19 CA148112]; Department
of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research
(CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen
Foundation; Breast Cancer Research Foundation; Ovarian Cancer Research
Fund; National Cancer Institute [UM1 CA164920, RC4CA153828]; Research
Council of Lithuania [LIG-07/2012]; Cancer Association of South Africa
(CANSA); Spanish Association against Cancer [AECC08, RTICC 06/0020/1060,
FISPI12/00070]; Mutua Madrilena Foundation (FMMA); City of Hope Clinical
Cancer Genetics Community Research Network and the Hereditary Cancer
Research Registry (COH-CCGCRN); Fondazione IRCCS Istituto Nazionale dei
Tumori; DKFZ; NIHR grant to the Biomedical Research Centre, Manchester;
NIHR grant to the Biomedical Research Centre at The Institute of Cancer
Research; Royal Marsden NHS Foundation Trust; German Cancer Aid
[109078]; Center for Molecular Medicine Cologne (CMMC); Ligue National
Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award;
Canadian Institutes of Health Research for the "CIHR Team in Familial
Risks of Breast Cancer" program; Helsinki University Central Hospital
Research Fund, Academy of Finland [266528]; Finnish Cancer Society and
the Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854,
NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific
Research [NWO 91109024]; Pink Ribbon [110005]; BBMRI [NWO
184.021.007/CP46]; Hungarian Research Grants [KTIA OTKA CK-80745, OTKA
K-112228]; Asociacion Espanola Contra el Cancer; Spanish Health Research
Fund; Carlos III Health Institute; Catalan Health Institute and
Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051,
RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, 2009SGR290];
Icelandic Association "Walking for Breast Cancer Research"; Landspitali
University Hospital Research Fund; Ministero della Salute; Istituto
Oncologico Veneto; National Breast Cancer Foundation; National Health
and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia;
Cancer Foundation of Western Australia; NCI Specialized Program of
Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department
of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; David and
Margaret T. Grohne Family Foundation; Ting Tsung and Wei Fong Chao
Foundation; Robert and Kate Niehaus Clinical Cancer Genetics Initiative;
Ohio State University Comprehensive Cancer Center; Swedish Cancer
Society; Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive
Cancer Institute - American Cancer Society Early Detection Professorship
[SIOP-06-258-01-COUN]; NEYE Foundation; European Union (European Social
Fund - ESF); Greek national funds through the Operational Program
"Education and Lifelong Learning" of the National Strategic Reference
Framework (NSRF) - Research Funding Program of the General Secretariat
for Research Technology:; University of Kansas Cancer Center [P30
CA168524]; Kansas Bioscience Authority Eminent Scholar Program; National
Cancer Institute grants to the Gynecologic Oncology Group (GOG)
Administrative Office and Tissue Bank [CA 27469]; GOG Statistical and
Data Center [CA 37517]; NCI's Community Clinical Oncology Program (CCOP)
grant [CA 101165]; Canadian Breast Cancer Research Alliance-grant
[019511]; Ministry of Economic Development, Innovation and Export Trade
- grant [PSR-SIIRI-701]; Israel Cancer Association; Israeli Inherited
Breast Cancer Consortium; Susan G. Komen Foundation; Basser Research
Center; ISCIII [RD12/00369/0006]; European Regional Development funds,
Spain; Morris and Horowitz Families Endowed Professorship; Chancellors
Distinguished Chair in Biomedical Sciences Professorship; Intramural
Research Program of the US National Cancer Institute; NIH; Westat, Inc;
[PBZ_KBN_122/P05/2004]; [1R01 CA149429-01]; [5U01CA113916];
[R01CA140323]; [NO2-CP-11019- 50]; [N02-CP-65504]; Associazione
Italiana per la Ricerca sul Cancro
FX Funding for the iCOGS infrastructure came from: the European Community's
Seventh Framework Programme under grant agreement no 223175
(HEALTH-F2-2009-223175; COGS), Cancer Research UK (C1287/A10118, C1287/A
10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/ A15007,
C5047/A10692), the NIH (CA128978) and Post-Cancer GWAS initiative
(1U19CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAMEON initiative),
the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of
Health Research (CIHR) for the CIHR Team in Familial Risks of Breast
Cancer, Komen Foundation for the Cure, the Breast Cancer Research
Foundation, and the Ovarian Cancer Research Fund. BCFR was supported by
grant UM1 CA164920 from the National Cancer Institute. BFBOCC was partly
supported by: Research Council of Lithuania grant LIG-07/2012; BRCA-gene
mutations and breast cancer in South African women (BMBSA) was supported
by grants from the Cancer Association of South Africa (CANSA) to
Elizabeth J. van Rensburg; the CNIO study was supported by Spanish
Association against Cancer (AECC08), RTICC 06/0020/1060 and
FISPI12/00070 and Mutua Madrilena Foundation (FMMA); City of Hope
Clinical Cancer Genetics Community Research Network and the Hereditary
Cancer Research Registry (COH-CCGCRN) was supported in part by Award
Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute
and the Office of the Director, NIH. CONSIT TEAM was partially supported
by funds from Italian citizens who allocated the 5 x 1000 share of their
tax payment in support of the Fondazione IRCCS Istituto Nazionale dei
Tumori, according to Italian laws (INT-Institutional strategic projects
'5 x 1000'); the DKFZ study was supported by the DKFZ; EMBRACE was
supported by Cancer Research UK Grants C1287/A10118, C1287/A16563 and
C1287/A17523. D. Gareth Evans and Fiona Lalloo are supported by an NIHR
grant to the Biomedical Research Centre, Manchester. The Investigators
at The Institute of Cancer Research and The Royal Marsden NHS Foundation
Trust were supported by an NIHR grant to the Biomedical Research Centre
at The Institute of Cancer Research and The Royal Marsden NHS Foundation
Trust. Ros Eeles and Elizabeth Bancroft were supported by Cancer
Research UK Grant C5047/A8385; the German Consortium of Hereditary
Breast and Ovarian Cancer (GC-HBOC) is kindly supported by the German
Cancer Aid to Rita K. Schmutzler (grant no. 109078) and by the Center
for Molecular Medicine Cologne (CMMC); the GEMO study was supported by
the Ligue National Contre le Cancer; the Association "Le cancer du sein,
parlons-en!" Award; and the Canadian Institutes of Health Research for
the "CIHR Team in Familial Risks of Breast Cancer" program; the HEBCS
was financially supported by the Helsinki University Central Hospital
Research Fund, Academy of Finland (266528), the Finnish Cancer Society
and the Sigrid Juselius Foundation; The HEBON study was supported by the
Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756,
the Netherlands Organization of Scientific Research grant NWO 91109024,
the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.; 007/CP46;
Hungarian Breast and Ovarian Cancer Study (HUNBOCS) was supported by
Hungarian Research Grants KTIA OTKA CK-80745 and OTKA K-112228; ICO was
sponsored by Asociacion Espanola Contra el Cancer, Spanish Health
Research Fund; Carlos III Health Institute; Catalan Health Institute and
Autonomous Government of Catalonia, contract grant numbers: ISCIIIRETIC
RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, and
2009SGR290; The IHCC was supported by Grant PBZ_KBN_122/P05/2004; The
ILUH group was supported by the Icelandic Association "Walking for
Breast Cancer Research" and by the Landspitali University Hospital
Research Fund; IOVHBOCS was supported by Ministero della Salute and "5 x
1000" Istituto Oncologico Veneto grant; kConFab was supported by grants
from the National Breast Cancer Foundation, the National Health and
Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the
Cancer Councils of New South Wales, Victoria, Tasmania and South
Australia, and the Cancer Foundation of Western Australia; MAYO was
supported by NIH grant CA128978, an NCI Specialized Program of Research
Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of
Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and a grant from
the Breast Cancer Research Foundation, the David and Margaret T. Grohne
Family Foundation, and the Ting Tsung and Wei Fong Chao Foundation;
MSKCC was supported by grants from the Breast Cancer Research Foundation
and Robert and Kate Niehaus Clinical Cancer Genetics Initiative; OSUCCG
was supported by the Ohio State University Comprehensive Cancer Center;
SWE-BRCA collaborators are supported by the Swedish Cancer Society; the
Women's Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer
Institute was funded by the American Cancer Society Early Detection
Professorship (SIOP-06-258-01-COUN).; This work was supported by the
NEYE Foundation; by the European Union (European Social Fund - ESF) and
Greek national funds through the Operational Program "Education and
Lifelong Learning" of the National Strategic Reference Framework (NSRF)
- Research Funding Program of the General Secretariat for Research&
Technology: ARISTEIA, Investing in knowledge society through the
European Social Fund; by the University of Kansas Cancer Center (P30
CA168524) and the Kansas Bioscience Authority Eminent Scholar Program;
by National Cancer Institute grants to the Gynecologic Oncology Group
(GOG) Administrative Office and Tissue Bank (CA 27469), the GOG
Statistical and Data Center (CA 37517), and by NCI's Community Clinical
Oncology Program (CCOP) grant (CA 101165); by the Canadian Institutes of
Health Research for the "CIHR Team in Familial Risks of Breast Cancer"
program, the Canadian Breast Cancer Research Alliance-grant #019511 and
the Ministry of Economic Development, Innovation and Export Trade -
grant #PSR-SIIRI-701; through a grant by the Israel Cancer Association
and the funding for the Israeli Inherited Breast Cancer Consortium; by
NIH (R01-CA102776 and R01CA083855; by Breast Cancer Research Foundation;
by Susan G. Komen Foundation; by Basser Research Center; by
RD12/00369/0006 from ISCIII and the European Regional Development funds,
Spain and by 1R01 CA149429-01 grant.; Susan L. Neuhausen was partially
supported by the Morris and Horowitz Families Endowed Professorship;
Andrew K. Godwin was funded by 5U01CA113916, R01CA140323, and by the
Chancellors Distinguished Chair in Biomedical Sciences Professorship;
the research of Mark H Greene and Phuong L Mai was supported by the
Intramural Research Program of the US National Cancer Institute, NIH,
and by support services contracts NO2-CP-11019- 50 and N02-CP-65504 with
Westat, Inc, Rockville, MD.
NR 8
TC 3
Z9 3
U1 3
U2 29
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JAN
PY 2015
VL 24
IS 1
BP 308
EP 316
DI 10.1158/1055-9965.EPI-14-0532
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AZ1YG
UT WOS:000348030700038
PM 25336561
ER
PT J
AU Fleg, JL
Cooper, LS
Borlaug, BA
Haykowsky, MJ
Kraus, WE
Levine, BD
Pfeffer, MA
Pina, IL
Poole, DC
Reeves, GR
Whellan, DJ
Kitzman, DW
AF Fleg, Jerome L.
Cooper, Lawton S.
Borlaug, Barry A.
Haykowsky, Mark J.
Kraus, William E.
Levine, Benjamin D.
Pfeffer, Marc A.
Pina, Ileana L.
Poole, David C.
Reeves, Gordon R.
Whellan, David J.
Kitzman, Dalane W.
CA Natl Heart Lung Blood Inst Working
TI Exercise Training as Therapy for Heart Failure Current Status and Future
Directions
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE heart failure; therapy
ID PRESERVED EJECTION FRACTION; RANDOMIZED CONTROLLED-TRIAL; CARDIAC
RESYNCHRONIZATION THERAPY; VENTRICULAR SYSTOLIC FUNCTION; MUSCLE
BLOOD-FLOW; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; ELDERLY-PATIENTS;
REHABILITATION PROGRAM; OXYGEN-CONSUMPTION
C1 [Fleg, Jerome L.; Cooper, Lawton S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Borlaug, Barry A.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Haykowsky, Mark J.] Univ Alberta, Fac Rehabil Med, Edmonton, AB, Canada.
[Kraus, William E.] Duke Univ, Sch Med, Div Cardiol, Durham, NC USA.
[Levine, Benjamin D.] Univ Texas SW Med Ctr Dallas, Inst Exercise & Environm Med, Dallas, TX 75390 USA.
[Pfeffer, Marc A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Pina, Ileana L.] Albert Einstein Coll Med, Div Cardiol, Bronx, NY 10467 USA.
[Poole, David C.] Kansas State Univ, Dept Kinesiol, Manhattan, KS 66506 USA.
[Poole, David C.] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA.
[Reeves, Gordon R.; Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Div Cardiol, Philadelphia, PA 19107 USA.
[Kitzman, Dalane W.] Wake Forest Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC USA.
[Kitzman, Dalane W.] Wake Forest Sch Med, Dept Internal Med, Sect Geriatr, Winston Salem, NC USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8147, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov
FU AtCor Medical; Amgen; Celladon; Hamilton Health Sciences; Novartis;
Sanofi Aventis
FX Dr Borlaug reports research grant support from AtCor Medical and
consultancy for Amgen, Merck, GlaxoSmithKline, and Cardiokinetix. Dr
Pfeffer reports research grant support from Amgen, Celladon, Hamilton
Health Sciences, Novartis, and Sanofi Aventis and consultancy for
Aastrom, Abbott Vascular, Amgen, Bristol-Myers Squibb, Cerenis, Concert,
Keryx, Medtronic, Merck, Novartis, Roche, Servier, Teva, and University
of Oxford. The other authors report no conflicts
NR 92
TC 17
Z9 18
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD JAN
PY 2015
VL 8
IS 1
BP 209
EP 220
DI 10.1161/CIRCHEARTFAILURE.113.001420
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ3RX
UT WOS:000348145400025
PM 25605639
ER
PT J
AU Bal-Price, A
Crofton, KM
Sachana, M
Shafer, TJ
Behl, M
Forsby, A
Hargreaves, A
Landesmann, B
Lein, PJ
Louisse, J
Monnet-Tschudi, F
Paini, A
Rolaki, A
Schrattenholz, A
Sunol, C
van Thriel, C
Whelan, M
Fritsche, E
AF Bal-Price, Anna
Crofton, Kevin M.
Sachana, Magdalini
Shafer, Timothy J.
Behl, Mamta
Forsby, Anna
Hargreaves, Alan
Landesmann, Brigitte
Lein, Pamela J.
Louisse, Jochem
Monnet-Tschudi, Florianne
Paini, Alicia
Rolaki, Alexandra
Schrattenholz, Andre
Sunol, Cristina
van Thriel, Christoph
Whelan, Maurice
Fritsche, Ellen
TI Putative adverse outcome pathways relevant to neurotoxicity
SO CRITICAL REVIEWS IN TOXICOLOGY
LA English
DT Review
DE adverse outcome pathway; in vitro testing; key events; molecular
initiating event; pathways of neurotoxicity; predictive toxicology
ID POSTOPERATIVE COGNITIVE DYSFUNCTION; ESTROGEN-RECEPTOR BINDING;
DEVELOPMENTAL NEUROTOXICITY; RISK-ASSESSMENT; NERVOUS-SYSTEM;
ALTERNATIVE METHODS; MAGNETIC-RESONANCE; MATURE HIPPOCAMPUS; PROGENITOR
CELLS; ANIMAL-MODELS
AB The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.
C1 [Bal-Price, Anna; Sachana, Magdalini; Landesmann, Brigitte; Louisse, Jochem; Paini, Alicia; Rolaki, Alexandra; Whelan, Maurice] European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, Ispra, Italy.
[Crofton, Kevin M.; Shafer, Timothy J.] US EPA, Off Res & Dev, Natl Ctr Computat Toxicol, Res Triangle Pk, NC USA.
[Behl, Mamta] Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Res Triangle Pk, NC USA.
[Forsby, Anna] Stockholm Univ, Arrhenius Labs NaturalSci, Dept Neurochem, S-10691 Stockholm, Sweden.
[Forsby, Anna] Swedish Toxicol Sci Res Ctr, Swetox, Sodertalje, Sweden.
[Hargreaves, Alan] Nottingham Trent Univ, Nottingham, England.
[Lein, Pamela J.] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA.
[Monnet-Tschudi, Florianne] Univ Lausanne, Dept Physiol, Lausanne, Switzerland.
[Monnet-Tschudi, Florianne] Univ Lausanne, SCAHT, Lausanne, Switzerland.
[Schrattenholz, Andre] ProteoSys AG, Mainz, Germany.
[Sunol, Cristina] CIBERESP, IDIBAPS, IIBB CSIC, Inst Invest Biomed Barcelona, Barcelona, Spain.
[van Thriel, Christoph] IfADo Leibniz Res Ctr Working Environm & Human Fa, Dortmund, Germany.
[Fritsche, Ellen] IUF Leibniz Res Inst Environm Med, Dusseldorf, Germany.
RP Bal-Price, A (reprint author), Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, Syst Toxicol Unit,EURL ECVAM, TP 580,Via Fermi 1, I-21026 Ispra, VA, Italy.
EM anna.price@jrc.ec.europa
RI Crofton, Kevin/J-4798-2015;
OI Crofton, Kevin/0000-0003-1749-9971; Forsby, Anna/0000-0001-6298-201X;
Cristina, Sunol/0000-0001-9367-8483; Hargreaves,
Alan/0000-0001-9754-5477
FU European Commission
FX The employment affiliation of the authors is shown on the cover page.
The authors have sole responsibility for the writing and content of this
paper. The contributing authors were participants of the workshop
organized by the EURL ECVAM. The external workshop participants were
invited on the basis of a survey performed by EURL ECVAM neurotoxicity
experts of the latest literature to identify those with specific
expertise in the relevant research fields. The workshop organization was
financially supported by the European Commission, including the cost of
travelling and per diem of all invited external experts. The strategy
for preparing the report, the literature selected for review, the
conclusions drawn and the recommendations made are exclusively the
collective scientific output of the workshop participants and do not
necessarily represent the views of the participants' employers.
NR 66
TC 13
Z9 13
U1 4
U2 34
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1040-8444
EI 1547-6898
J9 CRIT REV TOXICOL
JI Crit. Rev. Toxicol.
PD JAN
PY 2015
VL 45
IS 1
BP 83
EP 91
DI 10.3109/10408444.2014.981331
PG 9
WC Toxicology
SC Toxicology
GA AZ4NN
UT WOS:000348199100005
PM 25605028
ER
PT J
AU Tayeira-DaSilya, AM
Jones, AM
Julien-Williams, P
Yao, JH
Stylianou, M
Moss, J
AF Tayeira-DaSilya, Angelo M.
Jones, Amanda M.
Julien-Williams, Patricia
Yao, Jianhua
Stylianou, Mario
Moss, Joel
TI Severity and outcome of cystic lung disease in women with tuberous
sclerosis complex
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS; TSC2 MUTATIONS; SIROLIMUS;
HETEROZYGOSITY; PREVALENCE; LYMPHANGIOMYOMATOSIS; STANDARDIZATION;
TRANSPLANTATION; PATHOGENESIS; DIAGNOSIS
AB What are the clinical features, severity, and rate of progression of lung disease in women with tuberous sclerosis and lymphangioleiomyomatosis (LAM) and how do they differ from patients with sporadic LAM?
Data from 94 tuberous sclerosis/LAM and 460 sporadic LAM women were compared. 40 tuberous sclerosis/LAM and 40 sporadic LAM patients were age- and lung function-matched, and changes in volume occupied by cysts (cyst score) and pulmonary function occurring over 6.5 years were evaluated.
Tuberous sclerosis/LAM patients had better lung function than sporadic LAM patients, but no difference was observed from sporadic LAM patients in yearly rates of change in forced expiratory volume in 1 s (-1.9 +/- 2.7 versus 1.9 +/- 1.9% predicted; p=0.302), diffusing capacity of the lung for CO (-2.1 +/- 2.8 versus -1.9 +/- 2.7% predicted; p=0.282) or cyst scores (+1.0 +/- 1.3 versus +1.4 +/- 1.7%, p=0.213). However, the proportion of patients with abnormal lung function and higher rates of FEVI decline was greater in sporadic LAM. Some young tuberous sclerosis/LAM patients (mean age 25.7 +/- 3 years) progressed rapidly from minimal to severe lung disease.
Tuberous sclerosis/LAM patients may experience abrupt declines in lung function. Consequently, women with tuberous sclerosis found to have lung cysts should undergo periodic functional and radiological testing to follow disease progression and determine need for therapy.
C1 [Tayeira-DaSilya, Angelo M.; Jones, Amanda M.; Julien-Williams, Patricia; Moss, Joel] NIH, Cardiovasc & Pulm Branch, Heart Lung & Blood Inst, Bethesda, MD 20892 USA.
[Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA.
[Stylianou, Mario] NIH, Off Biostat Res, Heart Lung & Blood Inst, Bethesda, MD 20892 USA.
RP Tayeira-DaSilya, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
FU National Institutes of Health, National Heart, Lung, and Blood Institute
FX This study was supported by the Intramural Research Program, National
Institutes of Health, National Heart, Lung, and Blood Institute.
NR 39
TC 0
Z9 0
U1 0
U2 2
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JAN
PY 2015
VL 45
IS 1
BP 171
EP 180
DI 10.1183/09031936.00088314
PG 10
WC Respiratory System
SC Respiratory System
GA AZ4GM
UT WOS:000348179800022
ER
PT J
AU Schully, SD
Lam, TK
Dotson, WD
Chang, CQ
Aronson, N
Birkeland, ML
Brewster, SJ
Boccia, S
Buchanan, AH
Calonge, N
Calzone, K
Djulbegovic, B
Goddard, KAB
Klein, RD
Klein, TE
Lau, J
Long, R
Lyman, GH
Morgan, RL
Palmer, CGS
Ling, MVR
Rubinstein, WS
Swen, JJ
Terry, SF
Williams, MS
Khoury, MJ
AF Schully, Sheri D.
Lam, Tram Kim
Dotson, W. David
Chang, Christine Q.
Aronson, Naomi
Birkeland, Marian L.
Brewster, Stephanie Jo
Boccia, Stefania
Buchanan, Adam H.
Calonge, Ned
Calzone, Kathleen
Djulbegovic, Benjamin
Goddard, Katrina A. B.
Klein, Roger D.
Klein, Teri E.
Lau, Joseph
Long, Rochelle
Lyman, Gary H.
Morgan, Rebecca L.
Palmer, Christina G. S.
Ling, Mary V. Re
Rubinstein, Wendy S.
Swen, Jesse J.
Terry, Sharon F.
Williams, Marc S.
Khoury, Muin J.
TI Evidence synthesis and guideline development in genomic medicine:
current status and future prospects
SO GENETICS IN MEDICINE
LA English
DT Article
DE evidence synthesis; genomic medicine; guideline development
ID INCIDENTAL FINDINGS; RECOMMENDATIONS; PHARMACOGENOMICS; CONSORTIUM;
QUALITY; CANCER; ERA
AB Purpose: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field.
Methods: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations). The workshop explored methods used in evidence synthesis and guideline development and initiated a dialogue to compare these methods and to assess whether they are consistent with the Institute of Medicine report "Clinical Practice Guidelines We Can Trust."
Results: The participating organizations that develop guidelines or recommendations all had policies to manage guideline development and group membership, and processes to address conflicts of interests. However, there was wide variation in the reliance on external reviews, regular updating of recommendations, and use of systematic reviews to assess the strength of scientific evidence.
Conclusion: Ongoing efforts are required to establish criteria for guideline development in genomic medicine as proposed by the Institute of Medicine.
C1 [Schully, Sheri D.; Lam, Tram Kim; Chang, Christine Q.; Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Dotson, W. David; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Gen, Atlanta, GA USA.
[Aronson, Naomi] Blue Cross Blue Shield Assoc, Technol Evaluat Ctr, Chicago, IL USA.
[Birkeland, Marian L.] Natl Comprehens Canc Network, Ft Washington, PA USA.
[Brewster, Stephanie Jo] Boston Childrens Hosp, Boston, MA USA.
[Boccia, Stefania] Univ Cattolica Sacro Cuore, Inst Publ Hlth, Sect Hyg, Rome, Italy.
[Buchanan, Adam H.] Duke Canc Inst, Durham, NC USA.
[Calonge, Ned] Colorado Trust, Denver, CO USA.
[Calzone, Kathleen] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Djulbegovic, Benjamin] Univ S Florida, Tampa, FL USA.
[Djulbegovic, Benjamin] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Djulbegovic, Benjamin] Res Inst, Tampa, FL USA.
[Goddard, Katrina A. B.] Kaiser Permanente NW, Portland, OR USA.
[Klein, Roger D.] Cleveland Clin, Dept Mol Pathol, Cleveland, OH 44106 USA.
[Klein, Teri E.] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA.
[Lau, Joseph] Brown Univ, Providence, RI 02912 USA.
[Long, Rochelle] Natl Inst Gen Med Sci, NIH, Bethesda, MD USA.
[Lyman, Gary H.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Morgan, Rebecca L.] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA.
[Palmer, Christina G. S.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Ling, Mary V. Re] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Rubinstein, Wendy S.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Swen, Jesse J.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Terry, Sharon F.] Genet Alliance, Washington, DC USA.
[Williams, Marc S.] Genom Med Inst, Danville, PA USA.
[Williams, Marc S.] Geisinger Hlth Syst, Genom Med Inst, Danville, PA USA.
RP Schully, SD (reprint author), NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM schullys@mail.nih.gov
RI Djulbegovic, Benjamin/I-3661-2012;
OI Djulbegovic, Benjamin/0000-0003-0671-1447; Dotson, William
David/0000-0002-9606-6594
FU National Institutes of Health [R24GM61374, U01GM 92666, U01HL 105198]
FX The authors are grateful to all of the workshop participants, who fully
engaged in the meeting discussions. In addition, the work presented here
was partially supported by National Institutes of Health grants
R24GM61374, U01GM 92666, and U01HL 105198. The findings and conclusions
in this article are those of the authors and do not necessarily reflect
the views of the Department of Health and Human Services.
NR 18
TC 4
Z9 4
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JAN
PY 2015
VL 17
IS 1
BP 63
EP 67
DI 10.1038/gim.2014.69
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA AY7MT
UT WOS:000347744900010
PM 24946156
ER
PT J
AU Ma, T
Yu, MY
Chen, ZY
Fei, CL
Shung, KK
Zhou, QF
AF Ma, Teng
Yu, Mingyue
Chen, Zeyu
Fei, Chunlong
Shung, K. Kirk
Zhou, Qifa
TI Multi-Frequency Intravascular Ultrasound (IVUS) Imaging
SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL
LA English
DT Article; Proceedings Paper
CT 23rd International Symposium on the Applications of Ferroelectrics
(ISAF)
CY MAY 12-16, 2014
CL Pennsylvania State Univ, Univ Pk, PA
HO Pennsylvania State Univ
ID OPTICAL COHERENCE TOMOGRAPHY; RADIOFREQUENCY DATA-ANALYSIS;
HIGH-FREQUENCY ULTRASOUND; COMPOSITE TRANSDUCER; PLAQUE MORPHOLOGY;
IN-VITRO; DESIGN; MHZ; CLASSIFICATION; CRYSTAL
AB Acute coronary syndrome (ACS) is frequently associated with the sudden rupture of a vulnerable atherosclerotic plaque within the coronary artery. Several unique physiological features, including a thin fibrous cap accompanied by a necrotic lipid core, are the targeted indicators for identifying the vulnerable plaques. Intravascular ultrasound (IVUS), a catheter-based imaging technology, has been routinely performed in clinics for more than 20 years to describe the morphology of the coronary artery and guide percutaneous coronary interventions. However, conventional IVUS cannot facilitate the risk assessment of ACS because of its intrinsic limitations, such as insufficient resolution. Renovation of the IVUS technology is essentially needed to overcome the limitations and enhance the coronary artery characterization. In this paper, a multi-frequency intravascular ultrasound (IVUS) imaging system was developed by incorporating a higher frequency IVUS transducer (80 to 150 MHz) with the conventional IVUS (30-50 MHz) system. The newly developed system maintains the advantage of deeply penetrating imaging with the conventional IVUS, while offering an improved higher resolution image with IVUS at a higher frequency. The prototyped multi-frequency catheter has a clinically compatible size of 0.95 mm and a favorable capability of automated image co-registration. In vitro human coronary artery imaging has demonstrated the feasibility and superiority of the multi-frequency IVUS imaging system to deliver a more comprehensive visualization of the coronary artery. This ultrasonic-only intravascular imaging technique, based on a moderate refinement of the conventional IVUS system, is not only cost-effective from the perspective of manufacturing and clinical practice, but also holds the promise of future translation into clinical benefits.
C1 [Ma, Teng; Yu, Mingyue; Chen, Zeyu; Shung, K. Kirk; Zhou, Qifa] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Ma, Teng; Yu, Mingyue; Chen, Zeyu; Shung, K. Kirk; Zhou, Qifa] Univ So Calif, Resource Ctr Med Ultrason Transducer Technol, NIH, Los Angeles, CA USA.
[Fei, Chunlong] Wuhan Univ, Sch Phys & Technol, Wuhan 430072, Hubei, Peoples R China.
RP Ma, T (reprint author), Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
EM qifazhou@usc.edu
FU National Institute of Health [P41-EB002182, R01-EB10090]
FX This work is supported by the National Institute of Health under grants
P41-EB002182 and R01-EB10090.
NR 32
TC 19
Z9 21
U1 3
U2 22
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0885-3010
EI 1525-8955
J9 IEEE T ULTRASON FERR
JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control
PD JAN
PY 2015
VL 62
IS 1
BP 97
EP 107
DI 10.1109/TUFFC.2014.006679
PG 11
WC Acoustics; Engineering, Electrical & Electronic
SC Acoustics; Engineering
GA AZ0PU
UT WOS:000347948000010
PM 25585394
ER
PT J
AU Bei, AK
Diouf, A
Miura, K
Larremore, DB
Ribacke, U
Tullo, G
Moss, EL
Neafsey, DE
Daniels, RF
Zeituni, AE
Nosamiefan, I
Volkman, SK
Ahouidi, AD
Ndiaye, D
Dieye, T
Mboup, S
Buckee, CO
Long, CA
Wirth, DF
AF Bei, Amy K.
Diouf, Ababacar
Miura, Kazutoyo
Larremore, Daniel B.
Ribacke, Ulf
Tullo, Gregory
Moss, Eli L.
Neafsey, Daniel E.
Daniels, Rachel F.
Zeituni, Amir E.
Nosamiefan, Iguosadolo
Volkman, Sarah K.
Ahouidi, Ambroise D.
Ndiaye, Daouda
Dieye, Tandakha
Mboup, Souleymane
Buckee, Caroline O.
Long, Carole A.
Wirth, Dyann F.
TI Immune Characterization of Plasmodium falciparum Parasites with a Shared
Genetic Signature in a Region of Decreasing Transmission
SO INFECTION AND IMMUNITY
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; RED-CELL SURFACE; INFECTED ERYTHROCYTES;
ACQUIRED-IMMUNITY; FLOW-CYTOMETRY; SEVERE DISEASE; BLOOD-STAGES;
IN-VITRO; MALARIA; ANTIBODIES
AB As the intensity of malaria transmission has declined, Plasmodium falciparum parasite populations have displayed decreased clonal diversity resulting from the emergence of many parasites with common genetic signatures (CGS). We have monitored such CGS parasite clusters from 2006 to 2013 in Thies, Senegal, using the molecular barcode. The first, and one of the largest observed clusters of CGS parasites, was present in 24% of clinical isolates in 2008, declined to 3.4% of clinical isolates in 2009, and then disappeared. To begin to explore the relationship between the immune responses of the population and the emergence and decline of specific parasite genotypes, we have determined whether antibodies to CGS parasites correlate with their prevalence. We measured (i) antibodies capable of inhibiting parasite growth in culture and (ii) antibodies recognizing the surfaces of infected erythrocytes (RBCs). IgG obtained from volunteers in 2009 showed increased reactivity to the surfaces of CGS-parasitized erythrocytes over IgG from 2008. Since P. falciparum EMP-1 (PfEMP-1) is a major variant surface antigen, we used var Ups quantitative reverse transcription-PCR (qRT-PCR) and sequencing with degenerate DBL1 alpha domain primers to characterize the var genes expressed by CGS parasites after short-term in vitro culture. CGS parasites show upregulation of UpsA var genes and 2-cysteine-containing PfEMP-1 molecules and express the same dominant var transcript. Our work indicates that the CGS parasites in this cluster express similar var genes, more than would be expected by chance in the population, and that there is year-to-year variation in immune recognition of surface antigens on CGS parasite-infected erythrocytes. This study lays the groundwork for detailed investigations of the mechanisms driving the expansion or contraction of specific parasite clones in the population.
C1 [Bei, Amy K.; Ribacke, Ulf; Daniels, Rachel F.; Nosamiefan, Iguosadolo; Volkman, Sarah K.; Wirth, Dyann F.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Bei, Amy K.; Ahouidi, Ambroise D.; Dieye, Tandakha; Mboup, Souleymane] Cheikh Anta Diop Univ, Le Dantec Hosp, Fac Med & Pharm, Lab Bacteriol & Virol, Dakar, Senegal.
[Diouf, Ababacar; Miura, Kazutoyo; Tullo, Gregory; Zeituni, Amir E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Larremore, Daniel B.; Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Larremore, Daniel B.; Buckee, Caroline O.] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA.
[Moss, Eli L.; Neafsey, Daniel E.; Daniels, Rachel F.; Volkman, Sarah K.; Wirth, Dyann F.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Volkman, Sarah K.] Simmons Coll, Boston, MA 02115 USA.
[Ndiaye, Daouda] Cheikh Anta Diop Univ, Fac Med & Pharm, Lab Parasitol & Mycol, Dakar, Senegal.
RP Wirth, DF (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA.
EM dfwirth@hsph.harvard.edu
FU ASTMH Centennial Travel Award; Bill and Melinda Gates Foundation;
Intramural Research Program of NIAID; NIH; PATH/Malaria Vaccine
Initiative; National Institute of General Medical Sciences [R21GM100207]
FX A.K.B. is funded by an ASTMH Centennial Travel Award. This work was
funded by the Bill and Melinda Gates Foundation. Partial support also
came from the Intramural Research Program of NIAID, NIH, and from the
PATH/Malaria Vaccine Initiative (to C.A.L.). D.B.L. and C.O.B. are
supported by award R21GM100207 from the National Institute of General
Medical Sciences.
NR 54
TC 2
Z9 2
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD JAN
PY 2015
VL 83
IS 1
BP 276
EP 285
DI 10.1128/IAI.01979-14
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AZ0SR
UT WOS:000347955500028
PM 25368109
ER
PT J
AU Sun, J
Zhao, XQ
Balu, N
Hippe, DS
Hatsukami, TS
Isquith, DA
Yamada, K
Neradilek, MB
Canton, G
Xue, YJ
Fleg, JL
Desvigne-Nickens, P
Klimas, MT
Padley, RJ
Vassileva, MT
Wyman, BT
Yuan, C
AF Sun, Jie
Zhao, Xue-Qiao
Balu, Niranjan
Hippe, Daniel S.
Hatsukami, Thomas S.
Isquith, Daniel A.
Yamada, Kiyofumi
Neradilek, Moni B.
Canton, Gador
Xue, Yunjing
Fleg, Jerome L.
Desvigne-Nickens, Patrice
Klimas, Michael T.
Padley, Robert J.
Vassileva, Maria T.
Wyman, Bradley T.
Yuan, Chun
TI Carotid magnetic resonance imaging for monitoring atherosclerotic plaque
progression: a multicenter reproducibility study
SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING
LA English
DT Article
DE Magnetic resonance imaging; Carotid artery; Atherosclerosis;
Reproducibility; Multicenter study
ID RICH NECROTIC CORE; SAMPLE-SIZE CALCULATION; LIPID-LOWERING THERAPY;
IN-VIVO; HIGH-RESOLUTION; QUANTITATIVE ASSESSMENT; AORTIC PLAQUES;
FIBROUS-CAP; SCAN-RESCAN; MRI
AB This study sought to determine the multicenter reproducibility of magnetic resonance imaging (MRI) and the compatibility of different scanner platforms in assessing carotid plaque morphology and composition. A standardized multi-contrast MRI protocol was implemented at 16 imaging sites (GE: 8; Philips: 8). Sixty-eight subjects (61 +/- A 8 years; 52 males) were dispersedly recruited and scanned twice within 2 weeks on the same magnet. Images were reviewed centrally using a streamlined semiautomatic approach. Quantitative volumetric measurements on plaque morphology (lumen, wall, and outer wall) and plaque tissue composition [lipid-rich necrotic core (LRNC), calcification, and fibrous tissue] were obtained. Inter-scan reproducibility was summarized using the within-subject standard deviation, coefficient of variation (CV) and intraclass correlation coefficient (ICC). Good to excellent reproducibility was observed for both morphological (ICC range 0.98-0.99) and compositional (ICC range 0.88-0.96) measurements. Measurement precision was related to the size of structures (CV range 2.5-4.9 % for morphology, 36-44 % for LRNC and calcification). Comparable measurement variability was found between the two platforms on both plaque morphology and tissue composition. In conclusion, good to excellent inter-scan reproducibility of carotid MRI can be achieved in multicenter settings with comparable measurement precision between platforms, which may facilitate future multicenter endeavors that use serial MRI to monitor atherosclerotic plaque progression.
C1 [Sun, Jie; Balu, Niranjan; Hippe, Daniel S.; Yamada, Kiyofumi; Xue, Yunjing; Yuan, Chun] Univ Washington, Dept Radiol, Seattle, WA 98109 USA.
[Zhao, Xue-Qiao; Isquith, Daniel A.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA USA.
[Hatsukami, Thomas S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Neradilek, Moni B.] Mt Whisper Light Stat, Seattle, WA USA.
[Canton, Gador] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
[Fleg, Jerome L.; Desvigne-Nickens, Patrice] NHLBI, NIH, Bethesda, MD 20892 USA.
[Klimas, Michael T.] Merck, Whitehouse Stn, NJ USA.
[Padley, Robert J.] Abbvie, N Chicago, IL USA.
[Vassileva, Maria T.] Fdn Natl Inst Hlth, Bethesda, MD USA.
[Wyman, Bradley T.] Pfizer, New London, CT USA.
RP Sun, J (reprint author), Univ Washington, Dept Radiol, 850 Republican St Brotman 127, Seattle, WA 98109 USA.
EM sunjie@u.washington.edu; cyuan@u.washington.edu
RI Canton, Gador/H-4227-2016; Sun, J./M-8778-2016
OI Canton, Gador/0000-0002-0594-2764;
FU Foundation for the National Institutes of Health Biomarkers Consortium;
Merck; Pfizer; Abbott; [R01HL088214]
FX This study was supported by a Grant from the Foundation for the National
Institutes of Health Biomarkers Consortium made possible by funds from
Merck, Pfizer, and Abbott, and by R01HL088214. Carotid coils were
provided by GE Healthcare and Philips Healthcare. This manuscript
represents the views of the authors and not necessarily those of the
National Institutes of Health or the United States government.
NR 33
TC 10
Z9 10
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1569-5794
EI 1573-0743
J9 INT J CARDIOVAS IMAG
JI Int. J. Cardiovasc. Imaging
PD JAN
PY 2015
VL 31
IS 1
BP 95
EP 103
DI 10.1007/s10554-014-0532-7
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AZ3JI
UT WOS:000348123000013
PM 25216871
ER
PT J
AU Sengupta, I
Gao, M
Arachchige, RJ
Nadaud, PS
Cunningham, TF
Saxena, S
Schwieters, CD
Jaroniec, CP
AF Sengupta, Ishita
Gao, Min
Arachchige, Rajith J.
Nadaud, Philippe S.
Cunningham, Timothy F.
Saxena, Sunil
Schwieters, Charles D.
Jaroniec, Christopher P.
TI Protein structural studies by paramagnetic solid-state NMR spectroscopy
aided by a compact cyclen-type Cu(II) binding tag
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Solid-state NMR; Magic-angle spinning; Paramagnetic relaxation; Metal
binding tag; Protein structure
ID TRANSITION-METAL-IONS; ANGLE-SPINNING NMR; PSEUDOCONTACT SHIFTS;
MEMBRANE-PROTEINS; DYNAMICS; SITE; RESTRAINTS; DISTANCE; ACID;
GENERATION
AB Paramagnetic relaxation enhancements (PREs) are a rich source of structural information in protein solid-state NMR spectroscopy. Here we demonstrate that PRE measurements in natively diamagnetic proteins are facilitated by a thiol-reactive compact, cyclen-based, high-affinity Cu2+ binding tag, 1-[2-(pyridin-2-yldisulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (TETAC), that overcomes the key shortcomings associated with the use of larger, more flexible metal-binding tags. Using the TETAC-Cu2+ K28C mutant of B1 immunoglobulin-binding domain of protein G as a model, we find that amino acid residues located within similar to 10 angstrom of the Cu2+ center experience considerable transverse PREs leading to severely attenuated resonances in 2D N-15-C-13 correlation spectra. For more distant residues, electron-nucleus distances are accessible via quantitative measurements of longitudinal PREs, and we demonstrate such measurements for N-15-Cu2+ distances up to similar to 20 angstrom.
C1 [Sengupta, Ishita; Gao, Min; Arachchige, Rajith J.; Nadaud, Philippe S.; Jaroniec, Christopher P.] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA.
[Cunningham, Timothy F.; Saxena, Sunil] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA.
[Schwieters, Charles D.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Jaroniec, CP (reprint author), Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA.
EM jaroniec@chemistry.ohio-state.edu
RI Jaroniec, Christopher/A-4948-2008; Gao, Min/H-9266-2015;
OI Jaroniec, Christopher/0000-0003-0364-2888; Saxena,
Sunil/0000-0001-9098-6114
FU National Science Foundation [MCB-1243461, MCB-1157712]; National
Institutes of Health [R01GM094357]; Camille & Henry Dreyfus Foundation
(Camille Dreyfus Teacher-Scholar Award); National Institutes of Health
Intramural Research Program of the Center for Information Technology
FX This work was supported by grants from the National Science Foundation
(MCB-1243461 to C.P.J. and MCB-1157712 to S.S.), the National Institutes
of Health (R01GM094357 to C.P.J.) and the Camille & Henry Dreyfus
Foundation (Camille Dreyfus Teacher-Scholar Award to C.P.J.). C.D.S. was
supported by the National Institutes of Health Intramural Research
Program of the Center for Information Technology.
NR 52
TC 3
Z9 3
U1 3
U2 21
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
EI 1573-5001
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD JAN
PY 2015
VL 61
IS 1
BP 1
EP 6
DI 10.1007/s10858-014-9880-9
PG 6
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA AZ7UY
UT WOS:000348424400001
PM 25432438
ER
PT J
AU Longobardi, E
Rossi-Arnaud, C
Spataro, P
Putnick, DL
Bornstein, MH
AF Longobardi, Emiddia
Rossi-Arnaud, Clelia
Spataro, Pietro
Putnick, Diane L.
Bornstein, Marc H.
TI Children's acquisition of nouns and verbs in Italian: contrasting the
roles of frequency and positional salience in maternal language
SO JOURNAL OF CHILD LANGUAGE
LA English
DT Article
ID EARLY LEXICAL DEVELOPMENT; GRAMMATICAL CATEGORIES; VOCABULARY
DEVELOPMENT; JAPANESE CHILDREN; UNIVERSAL GRAMMAR; YOUNG-CHILDREN;
UNITED-STATES; SPEECH; INFANTS; INPUT
AB Because of its structural characteristics, specifically the prevalence of verb types in infant-directed speech and frequent pronoun-dropping, the Italian language offers an attractive opportunity to investigate the predictive effects of input frequency and positional salience on children's acquisition of nouns and verbs. We examined this issue in a sample of twenty-six mother-child dyads whose spontaneous conversations were recorded, transcribed, and coded at 1;4 and 1;8 The percentages of nouns occurring in the final position of maternal utterances at 1;4 predicted children's production of noun types at 1;8. For verbs, children's growth rates were positively predicted by the percentages of input verbs occurring in utterance-initial position, but negatively predicted by the percentages of verbs located in the final position of maternal utterances at 1;4. These findings clearly illustrate that the effects of positional salience vary across lexical categories.
C1 [Longobardi, Emiddia] Univ Roma La Sapienza, Dept Dynam & Clin Psychol, I-00185 Rome, Italy.
[Rossi-Arnaud, Clelia; Spataro, Pietro] Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy.
[Putnick, Diane L.; Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Longobardi, E (reprint author), Univ Roma La Sapienza, Dept Dynam & Clin Psychol, Via Marsi 78, I-00185 Rome, Italy.
EM emiddia.longobardi@uniroma1.it
OI ROSSI-ARNAUD, Clelia /0000-0001-5006-6583; Putnick,
Diane/0000-0002-6323-749X
FU Intramural NIH HHS
NR 84
TC 5
Z9 5
U1 3
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0305-0009
EI 1469-7602
J9 J CHILD LANG
JI J. Child Lang.
PD JAN
PY 2015
VL 42
IS 1
BP 95
EP 121
DI 10.1017/S0305000913000597
PG 27
WC Psychology, Developmental; Linguistics; Psychology, Experimental
SC Psychology; Linguistics
GA CA2BK
UT WOS:000348713800004
PM 24524564
ER
PT J
AU Kruszka, P
Hart, RA
Hadley, DW
Muenke, M
Habal, MB
AF Kruszka, Paul
Hart, Rachel A.
Hadley, Donald W.
Muenke, Maximilian
Habal, Mutaz B.
TI Expanding the Phenotypic Expression of Sonic Hedgehog Mutations Beyond
Holoprosencephaly
SO JOURNAL OF CRANIOFACIAL SURGERY
LA English
DT Editorial Material
ID MANAGEMENT; RECOMMENDATIONS; PERSPECTIVES; CHILDREN
C1 [Kruszka, Paul; Hart, Rachel A.; Hadley, Donald W.; Muenke, Maximilian; Habal, Mutaz B.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
NR 21
TC 1
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1049-2275
EI 1536-3732
J9 J CRANIOFAC SURG
JI J. Craniofac. Surg.
PD JAN
PY 2015
VL 26
IS 1
BP 7
EP 9
DI 10.1097/SCS.0000000000001377
PG 3
WC Surgery
SC Surgery
GA AZ0SH
UT WOS:000347954400039
PM 25569381
ER
PT J
AU Zhu, N
Jacobs, DR
Meyer, KA
He, K
Launer, L
Reis, JP
Yaffe, K
Sidney, S
Whitmer, RA
Steffen, LM
AF Zhu, N.
Jacobs, D. R.
Meyer, K. A.
He, K.
Launer, L.
Reis, J. P.
Yaffe, K.
Sidney, S.
Whitmer, R. A.
Steffen, L. M.
TI COGNITIVE FUNCTION IN A MIDDLE AGED COHORT IS RELATED TO HIGHER QUALITY
DIETARY PATTERN 5 AND 25 YEARS EARLIER: THE CARDIA STUDY
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Cohort study; epidemiology; middle age; diet pattern; cognitive tests
ID ARTERY RISK DEVELOPMENT; YOUNG-ADULTS CARDIA; MEDITERRANEAN DIET;
ALZHEIMER-DISEASE; PHYSICAL-ACTIVITY; ASSOCIATION; IMPAIRMENT; HEALTH;
RECRUITMENT; POPULATION
AB Background: Preserving cognitive function is an important public health issue. We investigated whether dietary pattern associates with cognitive function in middle-age. Methods: We studied 2435 participants in the community-based Coronary Artery Risk Development in Young Adults ( CARDIA) study of black and white men and women aged 18-30 in 1985-86 ( year 0, Y0). We hypothesized that a higher A Priori Diet Quality Score, measured at Y0 and Y20, is associated with better cognitive function measured at Y25. The diet score incorporated 46 food groups ( each in servings/day) as the sum of quintile ranks of food groups rated beneficial, 0 for food groups rated neutral, and reversed quintile ranks for food groups rated adverse; higher score indicated better diet quality. Y25 cognitive testing included verbal memory (Rey Auditory-Verbal Learning Test ( RAVLT)), psychomotor speed ( Digit Symbol Substitution Test ( DSST)) and executive function ( Stroop). Results: Per 10-unit higher diet score at Y20, the RAVLT was 0.32 words recalled higher, the DSST was 1.76 digits higher, and the Stroop was 1.00 seconds+errors lower ( better performance) after adjusting for race, sex, age, clinic, and energy intake. Further adjustment for physical activity, smoking, education, and body mass index attenuated the association slightly. Diet score at Y0 and increase in diet score over 20 years were also positively associated with each cognitive test. Conclusions: A higher quality dietary pattern was associated with better cognitive function 5 years and even 25 years later in apparently healthy middle-aged adults.
C1 [Zhu, N.; Jacobs, D. R.; Steffen, L. M.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Meyer, K. A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[He, K.] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA.
[Launer, L.] NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA.
[Reis, J. P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD USA.
[Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sidney, S.; Whitmer, R. A.] Kaiser Permanente Div Res, Oakland, CA 94612 USA.
RP Jacobs, DR (reprint author), 1300 South 2nd St,Ste 300, Minneapolis, MN 55454 USA.
EM jacob004@umn.edu
FU National Heart, Lung, and Blood Institute [HHSN268201300025C,
HHSN268201300026C, HHSN268201300027C, HHSN268201300028C,
HHSN268201300029C, HHSN268200900041C]; Intramural Research Program of
the National Institute on Aging; [R01-HL-053560]
FX The Coronary Artery Risk Development in Young Adults Study (CARDIA) is
supported by contracts HHSN268201300025C, HHSN268201300026C,
HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and
HHSN268200900041C from the National Heart, Lung, and Blood Institute and
the Intramural Research Program of the National Institute on Aging, as
well as by a grant (R01-HL-053560).
NR 41
TC 5
Z9 5
U1 0
U2 5
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 JAN
PY 2015
VL 19
IS 1
BP 33
EP 38
PG 6
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA AZ1WD
UT WOS:000348024800005
PM 25560814
ER
PT J
AU Xu, Z
Wu, CC
Xie, F
Slysz, GW
Tolic, N
Monroe, ME
Petyuk, VA
Payne, SH
Fujimoto, GM
Moore, RJ
Fillmore, TL
Schepmoes, AA
Levine, DA
Townsend, RR
Davies, SR
Li, SQ
Ellis, M
Boja, E
Rivers, R
Rodriguez, H
Rodland, KD
Liu, T
Smith, RD
AF Xu, Zhe
Wu, Chaochao
Xie, Fang
Slysz, Gordon W.
Tolic, Nikola
Monroe, Matthew E.
Petyuk, Vladislav A.
Payne, Samuel H.
Fujimoto, Grant M.
Moore, Ronald J.
Fillmore, Thomas L.
Schepmoes, Athena A.
Levine, Douglas A.
Townsend, R. Reid
Davies, Sherri R.
Li, Shunqiang
Ellis, Matthew
Boja, Emily
Rivers, Robert
Rodriguez, Henry
Rodland, Karin D.
Liu, Tao
Smith, Richard D.
TI Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor
Peptidomes
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE protein degradation; peptidomics; proteases; tumor; ovarian cancer;
breast cancer; ischemia
ID MOLECULAR-WEIGHT PROTEOME; MASS-SPECTROMETRY; INTRACELLULAR PEPTIDES;
CONTROLLED PROTEOLYSIS; SOFTWARE PACKAGE; ACCURATE MASS; PROTEASOME;
SERUM; METHIONINE; IDENTIFICATION
AB Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective and robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high-throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with postexcision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics and provides insights not readily obtainable from such approaches.
C1 [Xu, Zhe; Wu, Chaochao; Xie, Fang; Slysz, Gordon W.; Monroe, Matthew E.; Petyuk, Vladislav A.; Payne, Samuel H.; Fujimoto, Grant M.; Moore, Ronald J.; Schepmoes, Athena A.; Rodland, Karin D.; Liu, Tao; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99354 USA.
[Tolic, Nikola; Fillmore, Thomas L.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99354 USA.
[Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA.
[Townsend, R. Reid; Davies, Sherri R.; Li, Shunqiang; Ellis, Matthew] Washington Univ, Dept Med, St Louis, MO 63130 USA.
[Boja, Emily; Rivers, Robert; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA.
RP Liu, T (reprint author), Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99354 USA.
EM tao.liu@pnnl.gov; dick.smith@pnnl.gov
RI Smith, Richard/J-3664-2012;
OI Smith, Richard/0000-0002-2381-2349; Petyuk,
Vladislav/0000-0003-4076-151X; Payne, Samuel/0000-0002-8351-1994
FU National Cancer Institute Clinical Proteomic Tumor Analysis Consortium
(CPTAC), National Institutes of Health [U24CA160019, P41GM103493];
Department of Defense Interagency [MIPR2DO89M2058]; Department of Energy
(DOE) Early Career Award; DOE [DE-AC05-76RL0 1830]
FX Portions of this work were supported by Grant U24CA160019, from the
National Cancer Institute Clinical Proteomic Tumor Analysis Consortium
(CPTAC), National Institutes of Health Grant P41GM103493, Department of
Defense Interagency Agreement MIPR2DO89M2058, and Department of Energy
(DOE) Early Career Award (to S.H.P.). The experimental work described
herein was performed in the Environmental Molecular Sciences Laboratory,
a national scientific user facility sponsored by the DOE and located at
Pacific Northwest National Laboratory, which is operated by Battelle
Memorial Institute for the DOE under Contract DE-AC05-76RL0 1830.
NR 52
TC 9
Z9 10
U1 1
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD JAN
PY 2015
VL 14
IS 1
BP 422
EP 433
DI 10.1021/pr500840w
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA AY3UA
UT WOS:000347506600036
PM 25350482
ER
PT J
AU Buerger, C
Senegas, J
Kabus, S
Carolus, H
Schulz, H
Agarwal, H
Turkbey, B
Choyke, PL
Renisch, S
AF Buerger, C.
Senegas, J.
Kabus, S.
Carolus, H.
Schulz, H.
Agarwal, H.
Turkbey, B.
Choyke, P. L.
Renisch, S.
TI Comparing nonrigid registration techniques for motion corrected MR
prostate diffusion imaging
SO MEDICAL PHYSICS
LA English
DT Article
DE non-rigid image registration; diffusion imaging; prostate
ID IMAGES; DISTORTION
AB Purpose: T-2-weighted magnetic resonance imaging (MRI) is commonly used for anatomical visualization in the pelvis area, such as the prostate, with high soft-tissue contrast. MRI can also provide functional information such as diffusion-weighted imaging (DWI) which depicts the molecular diffusion processes in biological tissues. The combination of anatomical and functional imaging techniques is widely used in oncology, e.g., for prostate cancer diagnosis and staging. However, acquisition-specific distortions as well as physiological motion lead to misalignments between T-2 and DWI and consequently to a reduced diagnostic value. Image registration algorithms are commonly employed to correct for such misalignment.
Methods: The authors compare the performance of five state-of-the-art nonrigid image registration techniques for accurate image fusion of DWI with T-2.
Results: Image data of 20 prostate patients with cancerous lesions or cysts were acquired. All registration algorithms were validated using intensity-based as well as landmark-based techniques.
Conclusions: The authors' results show that the "fast elastic image registration" provides most accurate results with a target registration error of 1.07 +/- 0.41 mm at minimum execution times of 11 +/- 1 s. (c) 2015 American Association of Physicists in Medicine.
C1 [Buerger, C.; Senegas, J.; Kabus, S.; Carolus, H.; Schulz, H.; Renisch, S.] Philips Res Hamburg, D-22335 Hamburg, Germany.
[Agarwal, H.] Philips Res North Amer, Briarcliff Manor, NY 10510 USA.
[Agarwal, H.; Turkbey, B.; Choyke, P. L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Buerger, C (reprint author), Philips Res Hamburg, D-22335 Hamburg, Germany.
EM christian.buerger@philips.com
NR 20
TC 0
Z9 0
U1 0
U2 6
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JAN
PY 2015
VL 42
IS 1
BP 69
EP 80
DI 10.1118/1.4903262
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AZ0TJ
UT WOS:000347957200007
PM 25563248
ER
PT J
AU Liu, JF
Wang, SJ
Turkbey, EB
Linguraru, MG
Yao, JH
Summers, RM
AF Liu, Jianfei
Wang, Shijun
Turkbey, Evrim B.
Linguraru, Marius George
Yao, Jianhua
Summers, Ronald M.
TI Computer-aided detection of renal calculi from noncontrast CT images
using TV-flow and MSER features
SO MEDICAL PHYSICS
LA English
DT Article
DE renal calculi; kidney stone; total variation flow; maximally stable
extremal regions; computer-aided detection
ID EXTRACOLONIC FINDINGS; VIRTUAL COLONOSCOPY; ANISOTROPIC DIFFUSION;
ASYMPTOMATIC ADULTS; KIDNEY-STONES; COLONOGRAPHY; SEGMENTATION;
MANAGEMENT; EFFICIENT; OUTCOMES
AB Purpose: Renal calculi are common extracolonic incidental findings on computed tomographic colonography (CTC). This work aims to develop a fully automated computer-aided diagnosis system to accurately detect renal calculi on CTC images.
Methods: The authors developed a total variation (TV) flow method to reduce image noise within the kidneys while maintaining the characteristic appearance of renal calculi. Maximally stable extremal region (MSER) features were then calculated to robustly identify calculi candidates. Finally, the authors computed texture and shape features that were imported to support vector machines for calculus classification. The method was validated on a dataset of 192 patients and compared to a baseline approach that detects calculi by thresholding. The authors also compared their method with the detection approaches using anisotropic diffusion and nonsmoothing.
Results: At a false positive rate of 8 per patient, the sensitivities of the new method and the baseline thresholding approach were 69% and 35% (p < 1e-3) on all calculi from 1 to 433 mm(3) in the testing dataset. The sensitivities of the detection methods using anisotropic diffusion and nonsmoothing were 36% and 0%, respectively. The sensitivity of the new method increased to 90% if only larger and more clinically relevant calculi were considered.
Conclusions: Experimental results demonstrated that TV-flow and MSER features are efficient means to robustly and accurately detect renal calculi on low-dose, high noise CTC images. Thus, the proposed method can potentially improve diagnosis. (c) 2015 American Association of Physicists in Medicine.
C1 [Liu, Jianfei; Wang, Shijun; Turkbey, Evrim B.; Yao, Jianhua; Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Linguraru, Marius George] Childrens Natl Hlth Syst Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Linguraru, Marius George] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20010 USA.
RP Summers, RM (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU Intramural Research Program of the National Institutes of Health,
Clinical Center
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Clinical Center. The authors thank Dr.
Perry Pickhardt, Dr. J. Richard Choi, and Dr. William Schindler for
providing CT colonography data.
NR 49
TC 3
Z9 3
U1 1
U2 6
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JAN
PY 2015
VL 42
IS 1
BP 144
EP 153
DI 10.1118/1.4903056
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AZ0TJ
UT WOS:000347957200014
PM 25563255
ER
PT J
AU Gudino, N
Sonmez, M
Yao, Z
Baig, T
Nielles-Vallespin, S
Faranesh, AZ
Lederman, RJ
Martens, M
Balaban, RS
Hansen, MS
Griswold, MA
AF Gudino, N.
Sonmez, M.
Yao, Z.
Baig, T.
Nielles-Vallespin, S.
Faranesh, A. Z.
Lederman, R. J.
Martens, M.
Balaban, R. S.
Hansen, M. S.
Griswold, M. A.
TI Parallel transmit excitation at 1.5 T based on the minimization of a
driving function for device heating
SO MEDICAL PHYSICS
LA English
DT Article
DE RF heating; parallel transmission
ID MRI-GUIDED INTERVENTIONS; CURRENT AMPLITUDE; RF SAFETY; WIRES; FIELD;
COIL; AMPLIFICATION; REDUCTION; CATHETER; MONITOR
AB Purpose: To provide a rapid method to reduce the radiofrequency (RF) E-field coupling and consequent heating in long conductors in an interventional MRI (iMRI) setup.
Methods: A driving function for device heating (W) was defined as the integration of the E-field along the direction of the wire and calculated through a quasistatic approximation. Based on this function, the phases of four independently controlled transmit channels were dynamically changed in a 1.5 T MRI scanner. During the different excitation configurations, the RF induced heating in a nitinol wire immersed in a saline phantom was measured by fiber-optic temperature sensing. Additionally, a minimization of W as a function of phase and amplitude values of the different channels and constrained by the homogeneity of the RF excitation field (B-1) over a region of interest was proposed and its results tested on the benchtop. To analyze the validity of the proposed method, using a model of the array and phantom setup tested in the scanner, RF fields and SAR maps were calculated through finite-difference time-domain (FDTD) simulations. In addition to phantom experiments, RF induced heating of an active guidewire inserted in a swine was also evaluated.
Results: In the phantom experiment, heating at the tip of the device was reduced by 92% when replacing the body coil by an optimized parallel transmit excitation with same nominal flip angle. In the benchtop, up to 90% heating reduction was measured when implementing the constrained minimization algorithm with the additional degree of freedom given by independent amplitude control. The computation of the optimum phase and amplitude values was executed in just 12 s using a standard CPU. The results of the FDTD simulations showed similar trend of the local SAR at the tip of the wire and measured temperature as well as to a quadratic function of W, confirming the validity of the quasistatic approach for the presented problem at 64 MHz. Imaging and heating reduction of the guidewire were successfully performed in vivo with the proposed hardware and phase control.
Conclusions: Phantom and in vivo data demonstrated that additional degrees of freedom in a parallel transmission system can be used to control RF induced heating in long conductors. A novel constrained optimization approach to reduce device heating was also presented that can be run in just few seconds and therefore could be added to an iMRI protocol to improve RF safety. (c) 2015 American Association of Physicists in Medicine.
C1 [Gudino, N.; Griswold, M. A.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA.
[Gudino, N.; Sonmez, M.; Nielles-Vallespin, S.; Faranesh, A. Z.; Lederman, R. J.; Balaban, R. S.; Hansen, M. S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Yao, Z.; Baig, T.; Martens, M.] Case Western Reserve Univ, Dept Phys, Cleveland, OH 44106 USA.
[Griswold, M. A.] Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA.
RP Gudino, N (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA.
EM natalia.gudino@nih.gov
RI Hansen, Michael/J-5391-2015
OI Hansen, Michael/0000-0002-8087-8731
FU Siemens Healthcare; LFMI, NIH
FX The authors would like to acknowledge Siemens Healthcare for its
financial support. The author would also like to thank Jeffrey Duerk,
Kenneth Loparo, Robert Brown, Xin Yu, Peter Kellman, and Peter Van
Gelderen for their important feedback. To Katherine Lucas, Victor
Wright, Majdi Halabi, Bill Schenke, and Toby Rogers for their assistance
during animal experiments Finally, to the LFMI, NIH research group for
their help and constant support.
NR 29
TC 0
Z9 0
U1 0
U2 3
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JAN
PY 2015
VL 42
IS 1
BP 359
EP 371
DI 10.1118/1.4903894
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AZ0TJ
UT WOS:000347957200035
PM 25563276
ER
PT J
AU Chang, KE
Wei, BR
Madigan, JP
Hall, MD
Simpson, RM
Zhuang, ZP
Gottesman, MM
AF Chang, Ki-Eun
Wei, Bih-Rong
Madigan, James P.
Hall, Matthew D.
Simpson, R. Mark
Zhuang, Zhengping
Gottesman, Michael M.
TI The Protein Phosphatase 2A Inhibitor LB100 Sensitizes Ovarian Carcinoma
Cells to Cisplatin-Mediated Cytotoxicity
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID DNA-DAMAGE RESPONSE; PLATINUM COMPLEXES; INDUCED APOPTOSIS; CANCER;
RESISTANCE; LINES; PHOSPHORYLATION; REPAIR; CYCLE; MICE
AB Despite early positive response to platinum-based chemotherapy, the majority of ovarian carcinomas develop resistance and progress to fatal disease. Protein phosphatase 2A (PP2A) is a ubiquitous phosphatase involved in the regulation of DNA-damage response (DDR) and cell-cycle checkpoint pathways. Recent studies have shown that LB100, a small-molecule inhibitor of PP2A, sensitizes cancer cells to radiation-mediated DNA damage. We hypothesized that LB100 could sensitize ovarian cancer cells to cisplatin treatment. We performed in vitro studies in SKOV-3, OVCAR-8, and PEO1, -4, and -6 ovarian cancer lines to assess cytotoxicity potentiation, cell-death mechanism(s), cell-cycle regulation, and DDR signaling. In vivo studies were conducted in an intraperitoneal metastatic mouse model using SKOV-3/f-Luc cells. LB100 sensitized ovarian carcinoma lines to cisplatin-mediated cell death. Sensitization via LB100 was mediated by abrogation of cell-cycle arrest induced by cisplatin. Loss of the cisplatin-induced checkpoint correlated with decreased Wee1 expression, increased cdc2 activation, and increased mitotic entry (p-histone H3). LB100 also induced constitutive hyperphosphorylation of DDR proteins (BRCA1, Chk2, and gH2AX), altered the chronology and persistence of JNK activation, and modulated the expression of 14-3-3 binding sites. In vivo, cisplatin sensitization via LB100 significantly enhanced tumor growth inhibition and prevented disease progression after treatment cessation. Our results suggest that LB100 sensitizes ovarian cancer cells to cisplatin in vitro and in vivo by modulation of the DDR pathway and cell-cycle checkpoint abrogation. (C) 2014 AACR.
C1 [Chang, Ki-Eun; Madigan, James P.; Hall, Matthew D.; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20982 USA.
[Wei, Bih-Rong; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20982 USA.
[Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20982 USA.
EM mgottesman@nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
National Institute of Neurological Disorders and Stroke
FX This research was funded by the Intramural Research Program of the NIH,
the National Cancer Institute, and the National Institute of
Neurological Disorders and Stroke.
NR 53
TC 6
Z9 8
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JAN
PY 2015
VL 14
IS 1
BP 90
EP 100
DI 10.1158/1535-7163.MCT-14-0496
PG 11
WC Oncology
SC Oncology
GA AZ0MF
UT WOS:000347938700010
PM 25376608
ER
PT J
AU Sato, K
Hanaoka, H
Watanabe, R
Nakajima, T
Choyke, PL
Kobayashi, H
AF Sato, Kazuhide
Hanaoka, Hirofumi
Watanabe, Rira
Nakajima, Takahito
Choyke, Peter L.
Kobayashi, Hisataka
TI Near Infrared Photoimmunotherapy in the Treatment of Disseminated
Peritoneal Ovarian Cancer
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID IN-VIVO; PHOTODYNAMIC THERAPY; MONOCLONAL-ANTIBODY; TARGETED THERAPY;
BIOLUMINESCENCE; IMMUNOTHERAPY; SPHEROIDS; RETENTION; EFFICACY; MODELS
AB Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase-expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to NIR light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a three-dimensional (3D) spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these were assessed by tumor volume and/or bioluminescence. In vitro NIRPIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the antitumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs. control in tumor volume changes at day 10, P = 0.0001; NIR-PIT vs. control in luciferase activity at day 4, P = 0.0237), and the peritoneal model (NIR-PIT vs. control in luciferase activity at day 7, P = 0.0037). NIR-PIT provided effective cell killing in this HER2-positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors. (C) 2014 AACR.
C1 [Sato, Kazuhide; Hanaoka, Hirofumi; Watanabe, Rira; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,RoomB3B69,MSC1088, Bethesda, MD 20892 USA.
EM Kobayash@mail.nih.gov
FU NIH, NCI, Center for Cancer Research; JSPS
FX This work was supported by grants from the Intramural Research Program
of the NIH, NCI, Center for Cancer Research. Kazuhide Sato is supported
by a JSPS Research Fellowship for Japanese Biomedical and Behavioral
Researchers at NIH.
NR 36
TC 16
Z9 16
U1 1
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JAN
PY 2015
VL 14
IS 1
BP 141
EP 150
DI 10.1158/1535-7163.MCT-14-0658
PG 10
WC Oncology
SC Oncology
GA AZ0MF
UT WOS:000347938700015
PM 25416790
ER
PT J
AU Lahusen, TJ
Deng, CX
AF Lahusen, Tyler J.
Deng, Chu-Xia
TI SRT1720 Induces Lysosomal-Dependent Cell Death of Breast Cancer Cells
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID MITOCHONDRIAL-FUNCTION; MAMMALIAN SIRTUINS; DISEASE RELEVANCE; SIRT1;
TUMORIGENESIS; MICE; RESVERATROL; AUTOPHAGY; BRCA1; DEFICIENCY
AB SRT1720 is an activator of SIRT1, a NAD(+)-dependent protein and histone deacetylase that plays an important role in numerous biologic processes. Several studies have illustrated that SRT1720 treatment could improve metabolic conditions in mouse models and in a study in cancer SRT1720 caused increased apoptosis of myeloma cells. However, the effect of SRT1720 on cancer may be complex, as some recent studies have demonstrated that SRT1720 may not directly activate SIRT1 and another study showed that SRT1720 treatment could promote lung metastasis. To further investigate the role of SRT1720 in breast cancer, we treated SIRT1 knockdown and control breast cancer cell lines with SRT1720 both in vitro and in vivo. We showed that SRT1720 more effectively decreased the viability of basal-type MDA-MB-231 and BT20 cells as compared with luminal-type MCF-7 breast cancer cells or nontumorigenic MCF-10A cells. We demonstrated that SRT1720 induced lysosomal membrane permeabilization and necrosis, which could be blocked by lysosomal inhibitors. In contrast, SRT1720-induced cell death occurred in vitro irrespective of SIRT1 status, whereas in nude mice, SRT1720 exhibited a more profound effect in inhibiting the growth of allograft tumors of SIRT1 proficient cells as compared with tumors of SIRT1-deficient cells. Thus, SRT1720 causes lysosomal-dependent necrosis and may be used as a therapeutic agent for breast cancer treatment. (C) 2014 AACR.
C1 [Lahusen, Tyler J.; Deng, Chu-Xia] Natl Inst Diabet Digest & Kidney Dis, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Deng, CX (reprint author), Natl Inst Diabet Digest & Kidney Dis, NIH, Bldg 10,Room 9N-105, Bethesda, MD 20892 USA.
EM tylerlah@gmail.com; cxdeng@umac.mo
RI deng, chuxia/N-6713-2016
FU National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK),
Bethesda, MD
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK),
Bethesda, MD.
NR 44
TC 4
Z9 4
U1 3
U2 13
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JAN
PY 2015
VL 14
IS 1
BP 183
EP 192
DI 10.1158/1535-7163.MCT-14-0584
PG 10
WC Oncology
SC Oncology
GA AZ0MF
UT WOS:000347938700019
PM 25411356
ER
PT J
AU Lin, SR
Pan, CJ
Mansfield, BC
Chou, JY
AF Lin, Su Ru
Pan, Chi-Jiunn
Mansfield, Brian C.
Chou, Janice Yang
TI Functional analysis of mutations in a severe congenital neutropenia
syndrome caused by glucose-6-phosphatase-beta deficiency
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE G6PC3; Mutation analysis; Recombinant adenoviral vector
ID STORAGE-DISEASE TYPE-1A; G6PC3 MUTATIONS; GENE; DYSFUNCTION; IB; IA
AB Glucose-6-phosphatase-beta (G6Pase-beta or G6PC3) deficiency is characterized by neutropenia and dysfunction in both neutrophils and macrophages. G6Pase-beta is an enzyme embedded in the endoplasmic reticulum membrane that catalyzes the hydrolysis of glucose-6-phosphate (G6P) to glucose and phosphate. To date, 33 separate G6PC3 mutations have been identified in G6Pase-beta-deficient patients but only the p.R253H and p.G260R missense mutations have been characterized functionally for pathogenicity. Here we functionally characterize 16 of the 19 known missense mutations using a sensitive assay, based on a recombinant adenoviral vector-mediated expression system, to demonstrate pathogenicity. Fourteen missense mutations completely abolish G6Pase-beta enzymatic activity while the p.S139I and p.R189Q mutations retain 49% and 45%, respectively of wild type G6Pase-beta activity. A database of residual enzymatic activity retained by the G6Pase-beta mutations will serve as a reference for evaluating genotype phenotype relationships. Published by Elsevier Inc.
C1 [Lin, Su Ru; Pan, Chi-Jiunn; Mansfield, Brian C.; Chou, Janice Yang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD 21046 USA.
RP Chou, JY (reprint author), NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shiver National
Institute of Child Health and Human Development, National Institutes of
Health
FX The research was supported by the Intramural Research Program of the
Eunice Kennedy Shiver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 30
TC 1
Z9 1
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2015
VL 114
IS 1
BP 41
EP 45
DI 10.1016/j.ymgme.2014.11.012
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA AZ4GD
UT WOS:000348178900007
PM 25492228
ER
PT J
AU Ikawa, Y
Hess, R
Dorward, H
Cullinane, AR
Huizing, M
Gochuico, BR
Gahl, WA
Candotti, F
AF Ikawa, Yasuhiro
Hess, Richard
Dorward, Heidi
Cullinane, Andrew R.
Huizing, Marjan
Gochuico, Bernadette R.
Gahl, William A.
Candotti, Fabio
TI In vitro functional correction of Hermansky-Pudlak Syndrome type-1 by
lentiviral-mediated gene transfer
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Hermansky-Pudlak syndrome; Pulmonary fibrosis; Gene therapy; Lentivirus;
Melanocytes
ID MOUSE MODEL; CELLS; FIBROSIS; DISEASE; RAB38
AB Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, bleeding tendency and susceptibility to pulmonary fibrosis. No curative therapy is available. Genetic correction directed to the lungs, bone marrow and/or gastro-intestinal tract might provide alternative forms of treatment for the diseases multi-systemic complications. We demonstrate that lentiviral-mediated gene transfer corrects the expression and function of the HPS1 gene in patient dermal melanocytes, which opens the way to development of gene therapy for HPS. Published by Elsevier Inc.
C1 [Ikawa, Yasuhiro; Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Hess, Richard; Dorward, Heidi; Cullinane, Andrew R.; Huizing, Marjan; Gochuico, Bernadette R.; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Candotti, F (reprint author), Univ Lausanne Hosp, Div Immunol & Allergy, Rue Bugnon 46,BH10-513, CH-1011 Lausanne, Switzerland.
EM fabio.candotti@chuv.ch
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, USA [ZIA
HG000122]; UNIL-CHUV [CGRB 29583]
FX The authors thank Dr. Adrian J. Thrasher for providing the pHR'SINcPPT
construct and the 2.6-kb fragment of UCOE sequence from the human
HNRPA2B1-CBX locus (A2UCOE), and Dr. Inder Verma for the pMD.G,
pCMVDR8.91 plasmids. This research was supported by the Intramural
Research Program of the National Human Genome Research Institute,
National Institutes of Health, Bethesda, MD, USA (ZIA HG000122) and the
UNIL-CHUV grant no. CGRB 29583.
NR 15
TC 1
Z9 1
U1 3
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JAN
PY 2015
VL 114
IS 1
BP 62
EP 65
DI 10.1016/j.ymgme.2014.11.006
PG 4
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA AZ4GD
UT WOS:000348178900011
PM 25468649
ER
PT J
AU Lee, S
Lee, TA
Lee, E
Kang, S
Park, A
Kim, SW
Park, HJ
Yoon, JH
Ha, SJ
Park, T
Lee, JS
Cheon, JH
Park, B
AF Lee, Sungwook
Lee, Taeyun A.
Lee, Eunhye
Kang, Sujin
Park, Areum
Kim, Seung Won
Park, Hyo Jin
Yoon, Je-Hyun
Ha, Sang-Jun
Park, Taesun
Lee, Ju-Seog
Cheon, Jae Hee
Park, Boyoun
TI Identification of a subnuclear body involved in sequence-specific
cytokine RNA processing
SO NATURE COMMUNICATIONS
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; CAJAL BODIES; TDP-43; EXPRESSION;
OBESITY; SNRNPS; INTERLEUKIN-10; LOCALIZATION; AGGREGATION; METABOLISM
AB Processing of interleukin RNAs must be tightly controlled during the immune response. Here we report that a subnuclear body called the interleukin-6 and -10 splicing activating compartment (InSAC) is a nuclear site of cytokine RNA production and stability. Tat-activating regulatory DNA-binding protein-43 (TDP-43) acts as an InSAC scaffold that selectively associates with IL-6 and IL-10 RNAs in a sequence-specific manner. TDP-43 also recruits key spliceosomal components from Cajal bodies. LPS induces posttranslational modifications of TDP-43; in particular, TDP-43 ubiquitination provides a driving force for InSAC formation. As a consequence, in vivo depletion of TDP-43 leads to a dramatic reduction in the RNA processing and the protein levels of IL-6 in serum. Collectively, our findings highlight the importance of TDP-43-mediated InSAC biogenesis in immune regulation.
C1 [Lee, Sungwook; Lee, Taeyun A.; Lee, Eunhye; Kang, Sujin; Park, Areum; Park, Boyoun] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Syst Biol, Seoul 120749, South Korea.
[Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Dept Internal Med, Seoul 120752, South Korea.
[Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Inst Gastroenterol, Seoul 120752, South Korea.
[Kim, Seung Won; Cheon, Jae Hee] Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul 120752, South Korea.
[Park, Hyo Jin] Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biochem, Seoul 120749, South Korea.
[Yoon, Je-Hyun] Natl Inst Aging Intramural Res Program, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Park, Hyo Jin] Yonsei Univ, Coll Human Ecol, Dept Food & Nutr, Seoul 120749, South Korea.
[Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77054 USA.
RP Park, B (reprint author), Yonsei Univ, Coll Life Sci & Biotechnol, Dept Syst Biol, 50 Yonsei Ro, Seoul 120749, South Korea.
EM bypark@yonsei.ac.kr
RI Lee, Sungwook/K-3697-2013
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Education, Science and Technology
[2010-0009203, 2011-0015372]; National R&D Program for Cancer Control,
Ministry of Health & Welfare, Republic of Korea [1220060]; Korean Health
Technology R& D Project, Ministry of Health & Welfare, Republic of Korea
[HI14C2542]; Yonsei University Research Fund [2014-12-0135]; NIA-IRP,
NIH; Brain Korea (BK21) PLUS Program
FX We thank Dr Philip C. Wong (Departments of Pathology, Neuroscience and
Neurology, The Johns Hopkins University School of Medicine, Baltimore)
for critical reading of the manuscript, and Dr Alxander Hoffmann
(University of San Diego, USA) for NF-kappa B-deficient MEF cells. This
study was supported by grants from Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by the
Ministry of Education, Science and Technology (2010-0009203 and
2011-0015372), from the National R&D Program for Cancer Control,
Ministry of Health & Welfare, Republic of Korea (1220060), and from the
Korean Health Technology R& D Project, Ministry of Health & Welfare,
Republic of Korea (HI14C2542). S.L. and J.-H. Y. were supported by the
Yonsei University Research Fund of 2014 (2014-12-0135) and by the
NIA-IRP, NIH, respectively. S.L., S.K., T.A.L., E.L. and A.P. were
supported by Brain Korea (BK21) PLUS Program.
NR 40
TC 5
Z9 5
U1 1
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 JAN
PY 2015
VL 6
AR 5791
DI 10.1038/ncomms6791
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA1WQ
UT WOS:000348700100001
PM 25557830
ER
PT J
AU Pers, TH
Karjalainen, JM
Chan, Y
Westra, HJ
Wood, AR
Yang, J
Lui, JC
Vedantam, S
Gustafsson, S
Esko, T
Frayling, T
Speliotes, EK
Boehnke, M
Raychaudhuri, S
Fehrmann, RSN
Hirschhorn, JN
Franke, L
AF Pers, Tune H.
Karjalainen, Juha M.
Chan, Yingleong
Westra, Harm-Jan
Wood, Andrew R.
Yang, Jian
Lui, Julian C.
Vedantam, Sailaja
Gustafsson, Stefan
Esko, Tonu
Frayling, Tim
Speliotes, Elizabeth K.
Boehnke, Michael
Raychaudhuri, Soumya
Fehrmann, Rudolf S. N.
Hirschhorn, Joel N.
Franke, Lude
CA Genetic Invest ANthropometric Trai
TI Biological interpretation of genome-wide association studies using
predicted gene functions
SO NATURE COMMUNICATIONS
LA English
DT Article
ID CANDIDATE GENES; DATA SETS; DISEASE; NETWORK; LOCI; IDENTIFICATION;
ARCHITECTURE; INTEGRATION; HEIGHT; COMMON
AB The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.
C1 [Pers, Tune H.; Chan, Yingleong; Vedantam, Sailaja; Esko, Tonu; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Pers, Tune H.; Chan, Yingleong; Vedantam, Sailaja; Esko, Tonu; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.
[Pers, Tune H.; Chan, Yingleong; Vedantam, Sailaja; Esko, Tonu; Hirschhorn, Joel N.] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA.
[Karjalainen, Juha M.; Fehrmann, Rudolf S. N.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9711 Groningen, Netherlands.
[Chan, Yingleong; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Westra, Harm-Jan; Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
[Wood, Andrew R.] Univ Exeter, Sch Med, Exeter EX1 2LU, Devon, England.
[Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Yang, Jian] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4012, Australia.
[Lui, Julian C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Dev, Program Dev Endocrinol, NIH, Bethesda, MD 20892 USA.
[Gustafsson, Stefan] Uppsala Univ, Dept Med Sci Mol Epidemiol & Sci Life Lab, S-75185 Uppsala, Sweden.
[Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Speliotes, Elizabeth K.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Raychaudhuri, Soumya] Partners HealthCare Ctr Personalized Genet Med, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester M13 9PL, Lancs, England.
RP Pers, TH (reprint author), Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
EM tunepers@broadinstitute.org; joelh@broadinstitute.org; lude@ludesign.nl
RI Lui, Chun Kin Julian/E-2253-2012; Yang, Jian/A-5852-2010; Deloukas,
Panos/B-2922-2013; kinnunen, leena/B-7059-2012; Vermeulen,
H.H.M./L-4716-2015; de Bakker, Paul/B-8730-2009; Boehm,
Bernhard/F-8750-2015; Fehrmann, Rudolf/E-2551-2011; Gudnason,
Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; Sarzynski,
Mark/A-9798-2014; Bovet, Pascal/F-4477-2011; Bouchard,
Claude/A-7637-2009; Smith, Albert Vernon/K-5150-2015; Sundstrom,
Johan/A-6286-2009; Franke, Lude/P-7036-2016; Karjalainen,
Juha/P-8624-2016; Slagboom, P. Eline/R-4790-2016;
OI Yang, Jian/0000-0003-2001-2474; Deloukas, Panos/0000-0001-9251-070X;
kinnunen, leena/0000-0001-8739-4812; de Bakker,
Paul/0000-0001-7735-7858; Fehrmann, Rudolf/0000-0002-7516-315X;
Gudnason, Vilmundur/0000-0001-5696-0084; Bovet,
Pascal/0000-0002-0242-4259; Forouhi, Nita/0000-0002-5041-248X; Nothen,
Markus/0000-0002-8770-2464; Medina-Gomez, Carolina/0000-0001-7999-5538;
Ouwehand, Willem/0000-0002-7744-1790; Kaprio,
Jaakko/0000-0002-3716-2455; Hattersley, Andrew/0000-0001-5620-473X;
Peters, Annette/0000-0001-6645-0985; Beekman,
Marian/0000-0003-0585-6206; Esko, Tonu/0000-0003-1982-6569; Smith,
Albert Vernon/0000-0003-1942-5845; Deelen, Joris/0000-0003-4483-3701;
Locke, Adam/0000-0001-6227-198X; Mannisto, Satu/0000-0002-8668-3046;
Lakka, Timo/0000-0002-9199-2871; Folkersen, Lasse/0000-0003-0708-9530;
Humphries, Stephen E/0000-0002-8221-6547; Kumari,
Meena/0000-0001-9716-1035; Verweij, Niek/0000-0002-4303-7685; Sundstrom,
Johan/0000-0003-2247-8454; Franke, Lude/0000-0002-5159-8802; Slagboom,
P. Eline/0000-0002-2875-4723; Shungin, Dmitry/0000-0001-7900-5856;
Stanton, Alice/0000-0002-4961-165X; Kristiansson,
Kati/0000-0003-4688-107X; Moayyeri, Alireza/0000-0002-9143-2161; Magi,
Reedik/0000-0002-2964-6011; van der Velde, Nathalie/0000-0002-6477-6209;
van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153
FU Danish Council for Independent Research Medical Sciences (FSS) The
Alfred Benzon Foundation; Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH; Netherlands Organization for Scientific Research
[916-10135, 917-14374]; Horizon Breakthrough grant from the Netherlands
Genomics Initiative [92519031]; European Community's Health Seventh
Framework Programme (FP7) [259867]; National Institute of Diabetes and
Digestive and Kidney Diseases [2R01DK075787]
FX T.H.P. was supported by The Danish Council for Independent Research
Medical Sciences (FSS) The Alfred Benzon Foundation. J.C.L. was
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH.
L.F. was financially supported by grants from the Netherlands
Organization for Scientific Research (NWO-VENI grant 916-10135 and NWO
VIDI grant 917-14374) and a Horizon Breakthrough grant from the
Netherlands Genomics Initiative (grant 92519031). The research leading
to these results has received funding from the European Community's
Health Seventh Framework Programme (FP7/2007-2013) under grant agreement
no. 259867. We thank the DGI Consortium for making raw genotype and
phenotype data available, and the Global Lipids Genetics Consortium and
the International Inflammatory Bowel Disease Genetics Consortium for
making summary statistics available. We thank Drs. Ayellet V. Segre,
Elizabeth J. Rossin, Jeffrey Baron, Kasper Lage and Pascal Timshel for
helpful comments and discussions. This work was supported by The
National Institute of Diabetes and Digestive and Kidney Diseases
[2R01DK075787 to J.N.H.].
NR 39
TC 71
Z9 71
U1 8
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR 5890
DI 10.1038/ncomms6890
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA2MA
UT WOS:000348741300001
PM 25597830
ER
PT J
AU Vijai, J
Wang, ZM
Berndt, SI
Skibola, CF
Slager, SL
de Sanjose, S
Melbye, M
Glimelius, B
Bracci, PM
Conde, L
Birmann, BM
Wang, SS
Brooks-Wilson, AR
Lan, Q
de Bakker, PIW
Vermeulen, RCH
Portlock, C
Ansell, SM
Link, BK
Riby, J
North, KE
Gu, J
Hjalgrim, H
Cozen, W
Becker, N
Teras, LR
Spinelli, JJ
Turner, J
Zhang, YW
Purdue, MP
Giles, GG
Kelly, RS
Zeleniuch-Jacquotte, A
Ennas, MG
Monnereau, A
Bertrand, KA
Albanes, D
Lightfoot, T
Yeager, M
Chung, CC
Burdett, L
Hutchinson, A
Lawrence, C
Montalvan, R
Liang, LM
Huang, JY
Ma, B
Villano, DJ
Maria, A
Corines, M
Thomas, T
Novak, AJ
Dogan, A
Liebow, M
Thompson, CA
Witzig, TE
Habermann, TM
Weiner, GJ
Smith, MT
Holly, EA
Jackson, RD
Tinker, LF
Ye, Y
Adami, HO
Smedby, KE
De Roos, AJ
Hartge, P
Morton, LM
Severson, RK
Benavente, Y
Boffetta, P
Brennan, P
Foretova, L
Maynadie, M
Mckay, J
Staines, A
Diver, WR
Vajdic, CM
Armstrong, BK
Kricker, A
Zheng, TZ
Holford, TR
Severi, G
Vineis, P
Ferri, GM
Ricco, R
Miligi, L
Clavel, J
Giovannucci, E
Kraft, P
Virtamo, J
Smith, A
Kane, E
Roman, E
Chiu, BCH
Fraumeni, JF
Wu, XF
Cerhan, JR
Offit, K
Chanock, SJ
Rothman, N
Nieters, A
AF Vijai, Joseph
Wang, Zhaoming
Berndt, Sonja I.
Skibola, Christine F.
Slager, Susan L.
de Sanjose, Silvia
Melbye, Mads
Glimelius, Bengt
Bracci, Paige M.
Conde, Lucia
Birmann, Brenda M.
Wang, Sophia S.
Brooks-Wilson, Angela R.
Lan, Qing
de Bakker, Paul I. W.
Vermeulen, Roel C. H.
Portlock, Carol
Ansell, Stephen M.
Link, Brian K.
Riby, Jacques
North, Kari E.
Gu, Jian
Hjalgrim, Henrik
Cozen, Wendy
Becker, Nikolaus
Teras, Lauren R.
Spinelli, John J.
Turner, Jenny
Zhang, Yawei
Purdue, Mark P.
Giles, Graham G.
Kelly, Rachel S.
Zeleniuch-Jacquotte, Anne
Ennas, Maria Grazia
Monnereau, Alain
Bertrand, Kimberly A.
Albanes, Demetrius
Lightfoot, Tracy
Yeager, Meredith
Chung, Charles C.
Burdett, Laurie
Hutchinson, Amy
Lawrence, Charles
Montalvan, Rebecca
Liang, Liming
Huang, Jinyan
Ma, Baoshan
Villano, Danylo J.
Maria, Ann
Corines, Marina
Thomas, Tinu
Novak, Anne J.
Dogan, Ahmet
Liebow, Mark
Thompson, Carrie A.
Witzig, Thomas E.
Habermann, Thomas M.
Weiner, George J.
Smith, Martyn T.
Holly, Elizabeth A.
Jackson, Rebecca D.
Tinker, Lesley F.
Ye, Yuanqing
Adami, Hans-Olov
Smedby, Karin E.
De Roos, Anneclaire J.
Hartge, Patricia
Morton, Lindsay M.
Severson, Richard K.
Benavente, Yolanda
Boffetta, Paolo
Brennan, Paul
Foretova, Lenka
Maynadie, Marc
Mckay, James
Staines, Anthony
Diver, W. Ryan
Vajdic, Claire M.
Armstrong, Bruce K.
Kricker, Anne
Zheng, Tongzhang
Holford, Theodore R.
Severi, Gianluca
Vineis, Paolo
Ferri, Giovanni M.
Ricco, Rosalia
Miligi, Lucia
Clavel, Jacqueline
Giovannucci, Edward
Kraft, Peter
Virtamo, Jarmo
Smith, Alex
Kane, Eleanor
Roman, Eve
Chiu, Brian C. H.
Fraumeni, Joseph F.
Wu, Xifeng
Cerhan, James R.
Offit, Kenneth
Chanock, Stephen J.
Rothman, Nathaniel
Nieters, Alexandra
TI A genome-wide association study of marginal zone lymphoma shows
association to the HLA region
SO NATURE COMMUNICATIONS
LA English
DT Article
ID NON-HODGKIN-LYMPHOMA; EPIDEMIOLOGIC RESEARCH; RHEUMATOID-ARTHRITIS;
SUSCEPTIBILITY LOCI; FOLLICULAR LYMPHOMA; GASTRIC LYMPHOMA; CELL
DEVELOPMENT; GENE-EXPRESSION; RISK LOCI; CLASSIFICATION
AB Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P - 3.95 x 10(-15)) and HLA-B (rs2922994, P - 2.43 x 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
C1 [Vijai, Joseph; Portlock, Carol; Villano, Danylo J.; Maria, Ann; Corines, Marina; Thomas, Tinu; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
[Wang, Zhaoming; Yeager, Meredith; Burdett, Laurie; Hutchinson, Amy] NCI, Div Canc Epidemiol & Genet, Canc Genom Res Lab, Gaithersburg, MD 20877 USA.
[Berndt, Sonja I.; Lan, Qing; Purdue, Mark P.; Albanes, Demetrius; Chung, Charles C.; Hartge, Patricia; Morton, Lindsay M.; Fraumeni, Joseph F.; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Skibola, Christine F.; Conde, Lucia; Riby, Jacques] Sch Publ Hlth & Comprehens Canc Ctr, Dept Epidemiol, Birmingham, AL 35233 USA.
[Skibola, Christine F.; Conde, Lucia; Riby, Jacques; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Slager, Susan L.; Cerhan, James R.] Mayo Clin, Dept Hlth Sci, Rochester, MN 55905 USA.
[de Sanjose, Silvia; Benavente, Yolanda] IDIBELL, Inst Catala Oncol, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona 8907, Spain.
[de Sanjose, Silvia; Benavente, Yolanda] CIBERESP, Barcelona 8036, Spain.
[Melbye, Mads; Hjalgrim, Henrik] State Serum Inst, Dept Epidemiol Res, Div Hlth Surveillance & Res, Copenhagen 2300, Denmark.
[Melbye, Mads] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Glimelius, Bengt] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden.
[Glimelius, Bengt] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, S-75105 Uppsala, Sweden.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Sophia S.] City Hope Beckman Res Inst, Dept Canc Etiol, Duarte, CA 91030 USA.
[Brooks-Wilson, Angela R.] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Brooks-Wilson, Angela R.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 156, Canada.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, NL-3584 CG Utrecht, Netherlands.
[de Bakker, Paul I. W.; Vermeulen, Roel C. H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands.
[Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TD Utrecht, Netherlands.
[Ansell, Stephen M.; Novak, Anne J.; Liebow, Mark; Thompson, Carrie A.; Witzig, Thomas E.; Habermann, Thomas M.] Mayo Clin, Dept Med, Rochester, MN 55905 USA.
[Link, Brian K.; Weiner, George J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Gu, Jian; Ye, Yuanqing; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Becker, Nikolaus] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Teras, Lauren R.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Spinelli, John J.] British Columbia Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada.
[Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V6T 1Z3, Canada.
[Turner, Jenny] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia.
[Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, Macquarie Park, NSW 2113, Australia.
[Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT 06520 USA.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Kelly, Rachel S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London W2 1PG, England.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Inst Canc, New York, NY 10016 USA.
[Ennas, Maria Grazia] Univ Cagliari, Dept Biomed Sci, I-09042 Cagliari, Italy.
[Monnereau, Alain; Clavel, Jacqueline] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Environm Epidemiol Canc Grp, U1018, F-94807 Villejuif, France.
[Monnereau, Alain; Clavel, Jacqueline] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Monnereau, Alain] Inst Bergonie, Registre Hemopath Malignes Gironde, F-33076 Bordeaux, France.
[Bertrand, Kimberly A.; Liang, Liming; Huang, Jinyan; Ma, Baoshan; Adami, Hans-Olov; Giovannucci, Edward; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lightfoot, Tracy] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Lawrence, Charles; Montalvan, Rebecca; Smith, Alex; Kane, Eleanor; Roman, Eve] Hlth Studies Sect, Rockville, MD 20850 USA.
[Liang, Liming; Kraft, Peter] Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA.
[Ma, Baoshan] Dalian Maritime Univ, Coll Informat Sci & Technol, Dalian 116026, Peoples R China.
[Dogan, Ahmet] Mem Sloan Kettering Canc Ctr, Dept Lab Med & Pathol, New York, NY 10065 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Tinker, Lesley F.; De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98117 USA.
[Adami, Hans-Olov] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Smedby, Karin E.] Karolinska Inst, Dept Med Solna, S-17176 Stockholm, Sweden.
[De Roos, Anneclaire J.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI 48201 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Brennan, Paul] Int Agcy Res Canc, Genet Sect, Grp Genet Epidemiol, F-69372 Lyon, France.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic.
[Foretova, Lenka] MF MU, Brno 65653, Czech Republic.
[Maynadie, Marc] Univ Burgundy, Registre Hemopathies Malignes de Cote DOr, EA 4184, F-21070 Dijon, France.
[Maynadie, Marc] Dijon Univ Hosp, F-21070 Dijon, France.
[Mckay, James] Int Agcy Res Canc, Genet Sect, Genet Canc Susceptibil, F-69372 Lyon, France.
[Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.
[Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW 2052, Australia.
[Armstrong, Bruce K.; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Holford, Theodore R.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT 06520 USA.
[Dogan, Ahmet; Severi, Gianluca; Vineis, Paolo] Human Genet Fdn, I-10126 Turin, Italy.
[Ferri, Giovanni M.] Univ Bari, Interdisciplinary Dept Med, I-70124 Bari, Italy.
[Ricco, Rosalia] Univ Bari, Dept Pathol Anat, I-70124 Bari, Italy.
[Miligi, Lucia] Canc Prevent & Res Inst ISPO, Environm & Occupat Epidemiol Unit, I-50139 Florence, Italy.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FI-00271 Helsinki, Finland.
[Chiu, Brian C. H.] Univ Chicago, Dept Hlth Sci, Chicago, IL 60637 USA.
[Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79108 Freiburg, Germany.
RP Vijai, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA.
EM josephv@mskcc.org
RI Albanes, Demetrius/B-9749-2015; de Bakker, Paul/B-8730-2009; Armstrong,
Bruce/K-9464-2015; Conde, Lucia/D-9295-2011; Brooks-Wilson,
Angela/E-9399-2012; Purdue, Mark/C-9228-2016; de Sanjose Llongueras,
Silvia/H-6339-2014; Clavel, Jacqueline/Q-2750-2016;
OI Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; de Bakker,
Paul/0000-0001-7735-7858; Armstrong, Bruce/0000-0001-8940-7525;
Brooks-Wilson, Angela/0000-0003-1009-6408; Purdue,
Mark/0000-0003-1177-3108; Clavel, Jacqueline/0000-0002-3616-7676;
Staines, Anthony/0000-0001-9161-1357; Joseph, Vijai/0000-0002-7933-151X;
Giles, Graham/0000-0003-4946-9099
FU Intramural Research Program of the National Institutes of Health, NCI,
Division of Cancer Epidemiology and Genetics; U.S. Public Health Service
contracts [N01-CN-45165, N01-RC-45035, N01-RC-37004]; Canadian
Institutes for Health Research (CIHR); Canadian Cancer Society, Michael
Smith Foundation for Health Research; The American Cancer Society funds
the creation, maintenance and updating of the CPS-II cohort; National
Cancer Institute Surveillance Epidemiology and End Results program;
Leukaemia & Lymphoma Research; Fondation ARC pour la Recherche sur le
Cancer; Fondation de France; French Agency for Food, Environmental and
Occupational Health Safety (ANSES); French National Cancer Institute
(INCa); Coordinated Action [006438, SP23-CT-2005-006438]; HuGeF (Human
Genetics Foundation), Torino, Italy; EpiLymph-European Commission
[QLK4-CT-2000-00422, FOOD-CT-2006-023103]; Spanish Ministry of Health
[PI11/01810, C03/09, C03/10, RD06/0020/0095]; Marato de TV3 Foundation
[051210]; Agencia de Gestiod'AjutsUniversitarisi de Recerca-Generalitat
de Catalunya [2009SGR1465]; NIH [NO1-CO-12400]; Compagnia di San
Paolo-Programma Oncologia; Federal Office for Radiation Protection
grants [StSch4261, StSch4420]; Jose Carreras Leukemia Foundation
[DJCLS-R12/23]; German Federal Ministry for Education and Research
[BMBF-01-EO-1303]; Health Research Board, Ireland; Cancer Research
Ireland; MH CZ-DRO (MMCI) [00209805]; RECAMO [CZ.1.05/2.1.00/03.0101];
Association de Recherche Contre le Cancer; National Institutes of Health
[CA167552, CA97274, R01 CA92153, CA87969, CA49449, CA098122, CA098566,
K07 CA115687, 5R01 CA69669-02, RO1CA1046282, RO1CA154643]; Specialized
Programs of Research Excellence (SPORE) in Human Cancer [P50 CA97274];
Molecular Epidemiology of Non-Hodgkin Lymphoma Survival [R01 CA129539];
Henry J. Predolin Foundation; Italian Ministry for Education, University
and Research [2007WEJLZB, 20092ZELR2]; Italian Association for Cancer
Research (AIRC) [11855]; Regional Administration of Sardinia
[CRP-59812/2012]; Fondazione Banco di Sardegna [20102012]; National
Center for Advancing Translational Science [UL1 TR000135]; VicHealth;
Cancer Council Victoria; Australian NHMRC [209057, 251553, 504711];
Geoffrey Beene Cancer Research Grant, Lymphoma Foundation [LF5541];
Barbara K. Lipman Lymphoma Research Fund [74419]; Robert and Kate
Niehaus Clinical Cancer Genetics Research Initiative [57470, U01
HG007033]; NCI-SEER-Intramural Research Program of the National Cancer
Institute, National Institutes of Health; Public Health Service
[N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105];
Australian National Health and Medical Research Council [ID990920];
Cancer Council NSW; University of Sydney Faculty of Medicine;
NYU-WHS-National Cancer Institute [R01 CA098661, P30 CA016087]; National
Institute of Environmental Health Sciences [ES000260]; Intramural
Research Program of the National Cancer Institute; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS; Swedish Cancer Society
[2009/659]; Stockholm County Council [20110209]; Strategic Research
Program in Epidemiology at Karolinska Institute; Swedish Cancer Society
grant [02 6661]; Danish Cancer Research Foundation Grant; Lundbeck
Foundation Grant [R19-A2364]; Danish Cancer Society Grant [DP 08-155];
Plan Denmark; California Department of Health Services; National Cancer
Institute's Surveillance, Epidemiology and End Results Program
[HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]; Centers for
Disease Control and Prevention's National Program of Cancer Registries
[1U58 DP000807-01]; National Heart, Lung and Blood Institute, National
Institutes of Health, U.S. Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; National
Cancer Institute [CA62006]
FX Support for individual studies: ATBC-Intramural Research Program of the
National Institutes of Health, NCI, Division of Cancer Epidemiology and
Genetics. U.S. Public Health Service contracts (N01-CN-45165,
N01-RC-45035, N01-RC-37004); BCCA (J.J.S., A.R.B.-W.)-Canadian
Institutes for Health Research (CIHR). Canadian Cancer Society, Michael
Smith Foundation for Health Research; CPS-II (L.F.T.)-The American
Cancer Society funds the creation, maintenance and updating of the
CPS-II cohort. We thank the CPS-II participants and the Study Management
Group for their invaluable contributions to this research. We would also
like to acknowledge the contribution to this study from the central
cancer registries supported through the Centers for Disease Control and
Prevention National Program of Cancer Registries and cancer registries
supported by the National Cancer Institute Surveillance Epidemiology and
End Results program; ELCCS (E.R.)-Leukaemia & Lymphoma Research; ENGELA
(J.C.)-Fondation ARC pour la Recherche sur le Cancer. Fondation de
France. French Agency for Food, Environmental and Occupational Health &
Safety (ANSES), the French National Cancer Institute (INCa); EPIC
(E.R.)-Coordinated Action (Contract #006438, SP23-CT-2005-006438). HuGeF
(Human Genetics Foundation), Torino, Italy; EpiLymph-European Commission
(grant references QLK4-CT-2000-00422 and FOOD-CT-2006-023103); the
Spanish Ministry of Health (grant references CIBERESP, PI11/01810, RCESP
C03/09, RTICESP C03/10 and RTIC RD06/0020/0095), the Marato de TV3
Foundation (grant reference 051210), the Agencia de
Gestiod'AjutsUniversitarisi de Recerca-Generalitat de Catalunya (grant
reference 2009SGR1465) who had no role in the data collection, analysis
or interpretation of the results; the NIH (contract NO1-CO-12400); the
Compagnia di San Paolo-Programma Oncologia; the Federal Office for
Radiation Protection grants StSch4261 and StSch4420, the Jose Carreras
Leukemia Foundation grant DJCLS-R12/23, the German Federal Ministry for
Education and Research (BMBF-01-EO-1303); the Health Research Board,
Ireland and Cancer Research Ireland; Czech Republic supported by MH
CZ-DRO (MMCI, 00209805) and RECAMO, CZ.1.05/2.1.00/03.0101; Fondation de
France and Association de Recherche Contre le Cancer; HPFS (Walter C.
Willet)-The HPFS was supported in part by National Institutes of Health
grants CA167552, CA149445, CA098122, CA098566 (K.A.B.) and K07 CA115687
(B.M.B.). We would like to thank the participants and staff of the
Health Professionals Follow-up Study for their valuable contributions as
well as the following state cancer registries for their help: AL, AZ,
AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE,
NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. In
addition, this study was approved by the Connecticut Department of
Public Health (DPH) Human Investigations Committee. Certain data used in
this publication were obtained from the DPH. The authors assume full
responsibility for analyses and interpretation of these data; Iowa-Mayo
SPORE (G.J.W., J.R.C., T.E.W.)-National Institutes of Health (CA97274).
Specialized Programs of Research Excellence (SPORE) in Human Cancer (P50
CA97274). Molecular Epidemiology of Non-Hodgkin Lymphoma Survival (R01
CA129539). Henry J. Predolin Foundation; Italian GxE (P.C.)-Italian
Ministry for Education, University and Research (PRIN 2007
prot.2007WEJLZB, PRIN 2009 prot. 20092ZELR2); the Italian Association
for Cancer Research (AIRC, Investigator Grant 11855). (M.G.E.)-Regional
Law N.; 7, 2007: 'Basic research' (Progetti di ricerca fondamentale o di
base) by the Regional Administration of Sardinia (CRP-59812/2012),
Fondazione Banco di Sardegna 20102012; Mayo Clinic Case-Control
(J.R.C.)-National Institutes of Health (R01 CA92153). National Center
for Advancing Translational Science (UL1 TR000135); MCCS (G.G.G.,
G.S.)-The Melbourne Collaborative Cohort Study recruitment was funded by
VicHealth and Cancer Council Victoria. The MCCS was further supported by
Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure
provided by Cancer Council Victoria; MD Anderson (X.W.)-Institutional
support to the Center for Translational and Public Health Genomics;
MSKCC (K.O.)-Geoffrey Beene Cancer Research Grant, Lymphoma Foundation
(LF5541). Barbara K. Lipman Lymphoma Research Fund (74419). Robert and
Kate Niehaus Clinical Cancer Genetics Research Initiative (57470), U01
HG007033; NCI-SEER-Intramural Research Program of the National Cancer
Institute, National Institutes of Health, and Public Health Service
(N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105);
NHS (Meir J. Stampfer)-The NHS was supported in part by National
Institutes of Health grants CA87969, CA49449, CA149445, CA098122,
CA098566 (K.A.B.), and K07 CA115687 (B.M.B.). We would like to thank the
participants and staff of the Nurses' Health Study for their valuable
contributions as well as the following state cancer registries for their
help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME,
MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA,
WA, WY. In addition, this study was approved by the Connecticut
Department of Public Health (DPH) Human Investigations Committee.
Certain data used in this publication were obtained from the DPH. The
authors assume full responsibility for analyses and interpretation of
these data; NSW (C.M. Vajdic)-was supported by grants from the
Australian National Health and Medical Research Council (ID990920), the
Cancer Council NSW, and the University of Sydney Faculty of Medicine;
NYU-WHS-National Cancer Institute (R01 CA098661, P30 CA016087). National
Institute of Environmental Health Sciences (ES000260); PLCO-This
research was supported by the Intramural Research Program of the
National Cancer Institute and by contracts from the Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS; SCALE (K.E.S., H.O.A.,
H.H.)-Swedish Cancer Society (2009/659). Stockholm County Council
(20110209) and the Strategic Research Program in Epidemiology at
Karolinska Institute. Swedish Cancer Society grant (02 6661). Danish
Cancer Research Foundation Grant. Lundbeck Foundation Grant (R19-A2364).
Danish Cancer Society Grant (DP 08-155). National Institutes of Health
(5R01 CA69669-02). Plan Denmark; UCSF2 (C.F.S.)-National Institutes of
Health RO1CA1046282 and RO1CA154643; (E.A.H., P.M.B.; )-The collection
of cancer incidence data used in this study was supported by the
California Department of Health Services as part of the statewide cancer
reporting program mandated by California Health and Safety Code Section
103885; the National Cancer Institute's Surveillance, Epidemiology and
End Results Program under contract HHSN261201000140C awarded to the
Cancer Prevention Institute of California, contract HHSN261201000035C
awarded to the University of Southern California and contract
HHSN261201000034C awarded to the Public Health Institute; and the
Centers for Disease Control and Prevention's National Program of Cancer
Registries, under agreement #1U58 DP000807-01 awarded to the Public
Health Institute. The ideas and opinions expressed herein are those of
the authors, and endorsement by the State of California, the California
Department of Health Services, the National Cancer Institute, or the
Centers for Disease Control and Prevention or their contractors and
subcontractors is not intended nor should be inferred; WHI-WHI
investigators are: Program Office-(National Heart, Lung, and Blood
Institute, Bethesda, Maryland) Jacques Rossouw, Shari Ludlam, Dale
Burwen, Joan McGowan, Leslie Ford, and Nancy Geller; Clinical
Coordinating Center-(Fred Hutchinson Cancer Research Center, Seattle,
WA) Garnet Anderson, Ross Prentice, Andrea LaCroix, and Charles
Kooperberg; Investigators and Academic Centers-(Brigham and Women's
Hospital, Harvard Medical School, Boston, MA) JoAnn E. Manson; (MedStar
Health Research Institute/Howard University, Washington, DC) Barbara V.
Howard; (Stanford Prevention Research Center, Stanford, CA) Marcia L.
Stefanick; (The Ohio State University, Columbus, OH) Rebecca Jackson;
(University of Arizona, Tucson/Phoenix, AZ) Cynthia A. Thomson;
(University at Buffalo, Buffalo, NY) Jean Wactawski-Wende; (University
of Florida, Gainesville/Jacksonville, FL) Marian Limacher; (University
of Iowa, Iowa City/Davenport, IA) Robert Wallace; (University of
Pittsburgh, Pittsburgh, PA) Lewis Kuller; (Wake Forest University School
of Medicine, Winston-Salem, NC) Sally Shumaker; Women's Health
Initiative Memory Study-(Wake Forest University School of Medicine,
Winston-Salem, NC) Sally Shumaker. The WHI program is funded by the
National Heart, Lung and Blood Institute, National Institutes of Health,
U.S. Department of Health and Human Services through contracts
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C and HHSN271201100004C; YALE
(T.Z.)-National Cancer Institute (CA62006).
NR 39
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U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JAN
PY 2015
VL 6
AR UNSP 5751
DI 10.1038/ncomms6751
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA1BA
UT WOS:000348646500001
PM 25569183
ER
PT J
AU Rouault, TA
AF Rouault, Tracey A.
TI Mammalian iron-sulphur proteins: novel insights into biogenesis and
function
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID CYSTEINE DESULFURASE ACTIVITY; LINKED SIDEROBLASTIC ANEMIA; MULTIPLE
RESPIRATORY-CHAIN; FE-S PROTEINS; CLUSTER BIOGENESIS; SCAFFOLD PROTEIN;
FRIEDREICHS-ATAXIA; COMPLEX-II; PARAMAGNETIC-RESONANCE; MITOCHONDRIAL
DISEASE
AB Iron-sulphur (Fe-S) clusters are inorganic cofactors that are found in nearly all species and are composed of various combinations of iron and sulphur atoms. Fe-S clusters can accept or donate single electrons to carry out oxidation and reduction reactions and to facilitate electron transport. Many details of how these complex modular structures are assembled and ligated to cellular proteins in the mitochondrial, nuclear and cytosolic compartments of mammalian cells remain unclear. Recent evidence indicates that a Leu-Tyr-Arg (LYR) tripeptide motif found in some Fe-S recipient proteins may facilitate the direct and shielded transfer of Fe-S clusters from a scaffold to client proteins. Fe-S clusters are probably an unrecognized and elusive cofactor of many known proteins.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM Rouault@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, USA
FX This work was supported by the intramural programme of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, USA. The author thanks members of the Rouault group,
particularly N. Maio, G. Holmes-Hampton and W. Hang-Tong for their help
with the figures and narrative.
NR 111
TC 30
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U1 4
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
EI 1471-0080
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD JAN
PY 2015
VL 16
IS 1
BP 45
EP 55
DI 10.1038/nrm3909
PG 11
WC Cell Biology
SC Cell Biology
GA CA0ZU
UT WOS:000348642900008
PM 25425402
ER
PT J
AU Ligibel, JA
Alfano, CM
Courneya, KS
Demark-Wahnefried, W
Burger, RA
Chlebowski, RT
Fabian, CJ
Gucalp, A
Hershman, DL
Hudson, MM
Jones, LW
Kakarala, M
Ness, KK
Merrill, JK
Wollins, DS
Hudis, CA
AF Ligibel, Jennifer A.
Alfano, Catherine M.
Courneya, Kerry S.
Demark-Wahnefried, Wendy
Burger, Robert A.
Chlebowski, Rowan T.
Fabian, Carol J.
Gucalp, Ayca
Hershman, Dawn L.
Hudson, Melissa M.
Jones, Lee W.
Kakarala, Madhuri
Ness, Kirsten K.
Merrill, Janette K.
Wollins, Dana S.
Hudis, Clifford A.
TI American Society of Clinical Oncology Position Statement on Obesity and
Cancer EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Ligibel, Jennifer A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA.
[Courneya, Kerry S.] Univ Alberta, Edmonton, AB, Canada.
[Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Birmingham, AL USA.
[Burger, Robert A.] Univ Penn, Philadelphia, PA 19104 USA.
[Chlebowski, Rowan T.] Harbor Univ Calif Los Angeles Med Ctr, Torrance, CA USA.
[Fabian, Carol J.] Univ Kansas, Med Ctr, Westwood, KS USA.
[Gucalp, Ayca; Jones, Lee W.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY USA.
[Hudson, Melissa M.; Ness, Kirsten K.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Kakarala, Madhuri] Van Andel Inst, Grand Rapids, MI USA.
[Merrill, Janette K.; Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA USA.
RP Ligibel, JA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7828
EI 1533-9866
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD JAN
PY 2015
VL 70
IS 1
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AZ3QI
UT WOS:000348141400015
ER
PT J
AU Kuban, KCK
O'Shea, M
Allred, EN
Fichorova, RN
Heeren, T
Paneth, N
Hirtz, D
Dammann, O
Leviton, A
AF Kuban, Karl C. K.
O'Shea, Michael
Allred, Elizabeth N.
Fichorova, Raina N.
Heeren, Tim
Paneth, Nigel
Hirtz, Deborah
Dammann, Olaf
Leviton, Alan
CA ELGAN Study Investigators
TI The Breadth and Type of Systemic Inflammation and the Risk of Adverse
Neurological Outcomes in Extremely Low Gestation Newborns
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE extremely preterm infants; inflammation-related proteins; adverse
neurological outcomes; early life predictors of outcome
ID EXTREMELY PRETERM INFANTS; PERINATAL BRAIN-DAMAGE; CEREBRAL-PALSY;
IMMUNE CELLS; PROTEINS; INJURY; BLOOD; CHILDREN; AGE; HUMANS
AB BACKGROUND: We hypothesized that the risk of brain damage in extremely preterm neonates increases with the breadth and type of systemic inflammation, indexed by the number of elevated inflammation-related proteins and the number of functional categories of inflammation-related proteins exhibiting an elevated concentration. METHODS: In blood from 881 infants born before 28 weeks gestation, we measured the concentrations of 25 inflammation-related proteins, representing six functional categories (cytokines, chemokines, growth factors, adhesion molecules, metalloproteinases, and liver-produced acute phase reactant proteins) on postnatal days 1, 7, and 14. We evaluated associations between the number and type of proteins whose concentrations were elevated on two separate occasions a week apart and the diagnoses of ventriculomegaly as a neonate, and at 2 years, microcephaly, impaired early cognitive functioning, cerebral palsy, and autism risk as assessed with the Modified Checklist for Autism in Toddlers screen, and in a subset of these children from 12 of 14 sites (n = 826), an attention problem identified with the Child Behavior Checklist. RESULTS: The risk of abnormal brain structure and function overall was increased among children who had recurrent and/or persistent elevations of the 25 proteins. The risk for most outcomes did not rise until at least four proteins in at least two functional categories were elevated. When we focused our analysis on 10 proteins previously found to be associated consistently with neurological outcomes, we found the risk of low Mental Development Index on the Bayley Scales of Infant Development-II, microcephaly, and a Child Behavior Checklist-defined attention problem increased with higher numbers of these recurrently and/or persistently elevated proteins. INTERPRETATION: Increasing breadth of early neonatal inflammation, indexed by the number of protein elevations or the number of protein functional classes elevated, is associated with increasing risk of disorders of brain structure and function among infants born extremely preterm.
C1 [Kuban, Karl C. K.] Boston Med Ctr, Dept Pediat, Boston, MA 02118 USA.
[O'Shea, Michael] Wake Forest Sch Med, Dept Pediat, Winston Salem, NC USA.
[Allred, Elizabeth N.; Fichorova, Raina N.; Leviton, Alan] Harvard Univ, Sch Med, Boston, MA USA.
[Allred, Elizabeth N.; Leviton, Alan] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
[Allred, Elizabeth N.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Fichorova, Raina N.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Heeren, Tim] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Paneth, Nigel] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA.
[Dammann, Olaf] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
RP Kuban, KCK (reprint author), Boston Med Ctr, Dept Pediat, 1 Boston Med Ctr Pl,Dowling 3 South, Boston, MA 02118 USA.
EM karl.kuban@bmc.org
FU National Institute of Neurological Disorders and Stroke
[5U01NS040069-05, 2R01NS040069-08]
FX This study was supported by a cooperative agreement with the National
Institute of Neurological Disorders and Stroke (grants 5U01NS040069-05
and 2R01NS040069-08).
NR 49
TC 10
Z9 11
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD JAN
PY 2015
VL 52
IS 1
BP 42
EP 48
DI 10.1016/j.pediatrneurol.2014.10.005
PG 7
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA AZ7QA
UT WOS:000348411800006
PM 25459361
ER
PT J
AU Moaddel, R
Luckenbaugh, DA
Xie, Y
Villasenor, A
Brutsche, NE
Machado-Vieira, R
Ramamoorthy, A
Lorenzo, MP
Garcia, A
Bernier, M
Torjman, MC
Barbas, C
Zarate, CA
Wainer, IW
AF Moaddel, Ruin
Luckenbaugh, David A.
Xie, Ying
Villasenor, Alma
Brutsche, Nancy E.
Machado-Vieira, Rodrigo
Ramamoorthy, Anuradha
Paz Lorenzo, Maria
Garcia, Antonia
Bernier, Michel
Torjman, Marc C.
Barbas, Coral
Zarate, Carlos A., Jr.
Wainer, Irving W.
TI D-serine plasma concentration is a potential biomarker of (R,S)-ketamine
antidepressant response in subjects with treatment-resistant depression
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE (R,S)-ketamine; Antidepressant; Treatment-resistant depression; Bipolar
depression; D-serine; N-methyl-D-aspartate receptor; Serine racemase;
Plasma response marker
ID EXCITATORY AMINO-ACIDS; MAJOR DEPRESSION; FATTY-ACID; RECEPTOR
ANTAGONISTS; SERUM-LEVELS; KETAMINE; METABOLISM; DISORDER; RACEMASE;
GLYCINE
AB (R,S)-ketamine is a rapid and effective antidepressant drug that produces a response in two thirds of patients with treatment-resistant depression (TRD). The underlying biochemical differences between a (R,S)-ketamine responder (KET-R) and non-responder (KET-NR) have not been definitively identified but may involve serine metabolism.
The aim of the study was to examine the relationship between baseline plasma concentrations of D-serine and its precursor L-serine and antidepressant response to (R,S)-ketamine in TRD patients.
Plasma samples were obtained from 21 TRD patients at baseline, 60 min before initiation of the (R,S)-ketamine infusion. Patients were classified as KET-Rs (n = 8) or KET-NRs (n = 13) based upon the difference in Montgomery-sberg Depression Rating Scale (MADRS) scores at baseline and 230 min after infusion, with response defined as a a parts per thousand yen50 % decrease in MADRS score. The plasma concentrations of D-serine and L-serine were determined using liquid chromatography-mass spectrometry.
Baseline D-serine plasma concentrations were significantly lower in KET-Rs (3.02 +/- 0.21 mu M) than in KET-NRs (4.68 +/- 0.81 mu M), p < 0.001. A significant relationship between baseline D-serine plasma concentrations and percent change in MADRS at 230 min was determined using a Pearson correlation, r = 0.77, p < 0.001, with baseline D-serine explaining 60 % of the variance in (R,S)-ketamine response. The baseline concentrations of L-serine (L-Ser) in KET-Rs were also significantly lower than those measured in KET-NRs (66.2 +/- 9.6 mu M vs 242.9 +/- 5.6 mu M, respectively; p < 0.0001).
The results demonstrate that the baseline D-serine plasma concentrations were significantly lower in KET-Rs than in KET-NRs and suggest that this variable can be used to predict an antidepressant response following (R,S)-ketamine administration.
C1 [Moaddel, Ruin; Xie, Ying; Ramamoorthy, Anuradha; Bernier, Michel; Wainer, Irving W.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Luckenbaugh, David A.; Brutsche, Nancy E.; Machado-Vieira, Rodrigo; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Villasenor, Alma; Paz Lorenzo, Maria; Garcia, Antonia; Barbas, Coral] Univ CEU San Pablo, Fac Farm, Ctr Metabol & Bioanal CEMBIO, Madrid, Spain.
[Torjman, Marc C.; Wainer, Irving W.] Rowan Univ, Dept Anesthesiol, Cooper Med Sch, Camden, NJ USA.
[Wainer, Irving W.] NIA, Bioanalyt & Drug Discovery Unit, Lab Clin Invest, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Wainer, IW (reprint author), NIA, Bioanalyt & Drug Discovery Unit, Lab Clin Invest, NIH,Biomed Res Ctr, Suite 100,251 Bayview Boul, Baltimore, MD 21224 USA.
EM Wainerir@grc.nia.nih.gov
RI Garcia Fernandez, Antonia/C-4296-2008; MACHADO-VIEIRA,
RODRIGO/D-8293-2012;
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Bernier,
Michel/0000-0002-5948-368X
FU Intramural Research Program of the National Institute on Aging of the
National Institutes of Health (NIH); Intramural Research Program of the
National Institute of Mental Health of the National Institutes of Health
(NIH); Spanish Ministry of Science and Technology (MCIT)
[CTQ2011-23562]; EADS CASA
FX This work was supported in part by the Intramural Research Programs of
the National Institute on Aging (IWW) and National Institute of Mental
Health (CAZ) of the National Institutes of Health (NIH) and the Spanish
Ministry of Science and Technology (MCIT) grant CTQ2011-23562 (CB). A.
V. acknowledges her fellowship provided by EADS CASA.
NR 36
TC 11
Z9 11
U1 4
U2 27
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD JAN
PY 2015
VL 232
IS 2
BP 399
EP 409
DI 10.1007/s00213-014-3669-0
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AZ3IL
UT WOS:000348120700009
PM 25056852
ER
PT J
AU Simon, SL
Hoffman, FO
Hofer, E
AF Simon, Steven L.
Hoffman, F. Owen
Hofer, Eduard
TI The Two-Dimensional Monte Carlo: A New Methodologic Paradigm for Dose
Reconstruction for Epidemiological Studies
SO RADIATION RESEARCH
LA English
DT Article
ID EXPOSURE-MEASUREMENT ERROR; UTAH THYROID COHORT; RISK-ASSESSMENT;
INTERINDIVIDUAL VARIABILITY; CHERNOBYL ACCIDENT; JOINT PROPAGATION;
RESPONSE ANALYSES; UNCERTAINTY; DOSIMETRY; CANCER
AB Retrospective dose estimation, particularly dose reconstruction that supports epidemiological investigations of health risk, relies on various strategies that include models of physical processes and exposure conditions with detail ranging from simple to complex. Quantification of dose uncertainty is an essential component of assessments for health risk studies since, as is well understood, it is impossible to retrospectively determine the true dose for each person. To address uncertainty in dose estimation, numerical simulation tools have become commonplace and there is now an increased understanding about the needs and what is required for models used to estimate cohort doses (in the absence of direct measurement) to evaluate dose response. It now appears that for dose-response algorithms to derive the best, unbiased estimate of health risk, we need to understand the type, magnitude and interrelationships of the uncertainties of model assumptions, parameters and input data used in the associated dose estimation models. Heretofore, uncertainty analysis of dose estimates did not always properly distinguish between categories of errors, e. g., uncertainty that is specific to each subject (i.e., unshared error), and uncertainty of doses from a lack of understanding and knowledge about parameter values that are shared to varying degrees by numbers of subsets of the cohort. While mathematical propagation of errors by Monte Carlo simulation methods has been used for years to estimate the uncertainty of an individual subject's dose, it was almost always conducted without consideration of dependencies between subjects. In retrospect, these types of simple analyses are not suitable for studies with complex dose models, particularly when important input data are missing or otherwise not available. The dose estimation strategy presented here is a simulation method that corrects the previous deficiencies of analytical or simple Monte Carlo error propagation methods and is termed, due to its capability to maintain separation between shared and unshared errors, the two-dimensional Monte Carlo (2DMC) procedure. Simply put, the 2DMC method simulates alter-native, possibly true, sets (or vectors) of doses for an entire cohort rather than a single set that emerges when each individual's dose is estimated independently from other subjects. Moreover, estimated doses within each simulated vector maintain proper inter-relationships such that the estimated doses for members of a cohort subgroup that share common lifestyle attributes and sources of uncertainty are properly correlated. The 2DMC procedure simulates inter-individual variability of possibly true doses within each dose vector and captures the influence of uncertainty in the values of dosimetric parameters across multiple realizations of possibly true vectors of cohort doses. The primary characteristic of the 2DMC approach, as well as its strength, are defined by the proper separation between uncertainties shared by members of the entire cohort or members of defined cohort subsets, and uncertainties that are individual-specific and therefore unshared. (C) 2015 by Radiation Research Society
C1 [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hoffman, F. Owen] Oak Ridge Ctr Risk Anal, Oak Ridge, TN USA.
RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU National Cancer Institute Intramural Research Program; National
Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National
Cancer Institute [Y3-CO-5117]
FX This work was supported by the National Cancer Institute Intramural
Research Program and by the Intra-Agency Agreement between the National
Institute of Allergy and Infectious Diseases and the National Cancer
Institute, NIAID agreement Y2-Al-5077 and NCI agreement Y3-CO-5117. We
would like to acknowledge the contributions to this work by our
colleague Robert M. Weinstock (deceased). We also wish to thank our
numerous colleagues worldwide, especially those at the National Cancer
Institute and the Oak Ridge Center for Risk Analysis for assisting in a
variety of ways toward the development of our concepts and
understanding, as well as the implementation and presentation of the
example material presented here.
NR 54
TC 6
Z9 6
U1 1
U2 3
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 JAN
PY 2015
VL 183
IS 1
BP 27
EP 41
DI 10.1667/RR13729.1
PG 15
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA AZ0WI
UT WOS:000347962400002
PM 25496314
ER
PT J
AU Duncan, MW
Yergey, AL
Gale, PJ
AF Duncan, Mark W.
Yergey, Alfred L.
Gale, P. Jane
TI Quantifying Proteins by Mass Spectrometry
SO SPECTROSCOPY
LA English
DT Article
ID DIFFERENCE GEL-ELECTROPHORESIS; LINKED-IMMUNOSORBENT-ASSAY; MICROARRAY
TECHNOLOGY; QUANTITATIVE PROTEOMICS; INTERNAL STANDARD;
IMMUNOGLOBULIN-G; HIGH-RESOLUTION; HUMAN SERUM; QUANTIFICATION;
IMMUNOASSAY
AB The quantification of proteins in a complex biological sample is an important and challenging task. Mass spectrometry (MS) is increasingly used for this purpose, not only to give a global survey of the components and their amounts, but also to precisely and accurately quantify specific target proteins. Here, we review the essential elements of MS approaches to protein quantification and critically compare the available options.
C1 [Duncan, Mark W.] Univ Colorado, Sch Med, Boulder, CO 80309 USA.
[Duncan, Mark W.] Biodesix Inc, Boulder, CO USA.
[Duncan, Mark W.] King Saud Univ, Riyadh, Saudi Arabia.
[Yergey, Alfred L.] NICHD, Mass Spectrometry Facil, Bethesda, MD USA.
RP Duncan, MW (reprint author), Univ Colorado, Sch Med, Boulder, CO 80309 USA.
NR 44
TC 0
Z9 0
U1 2
U2 7
PU ADVANSTAR COMMUNICATIONS INC
PI DULUTH
PA 131 W 1ST STREET, DULUTH, MN 55802 USA
SN 0887-6703
J9 SPECTROSCOPY-US
JI Spectroscopy
PD JAN
PY 2015
VL 30
IS 1
BP 42
EP 58
PG 17
WC Spectroscopy
SC Spectroscopy
GA AZ4HF
UT WOS:000348181600006
ER
PT J
AU Chen, RT
Carbery, B
Mac, L
Berns, KI
Chapman, L
Condit, RC
Excler, JL
Gurwith, M
Hendry, M
Khan, AS
Khuri-Bulos, N
Klug, B
Robertson, JS
Seligman, SJ
Sheets, R
Williamson, AL
AF Chen, Robert T.
Carbery, Baevin
Mac, Lisa
Berns, Kenneth I.
Chapman, Louisa
Condit, Richard C.
Excler, Jean-Louis
Gurwith, Marc
Hendry, Michael
Khan, Arifa S.
Khuri-Bulos, Najwa
Klug, Bettina
Robertson, James S.
Seligman, Stephen J.
Sheets, Rebecca
Williamson, Anna-Lise
CA V3SWG
TI The Brighton Collaboration Viral Vector Vaccines Safety Working Group
(V3SWG)
SO VACCINE
LA English
DT Article
DE Vaccines; Viral Vector; Safety; Immunization
ID ROTAVIRUS VACCINE; HIV-1 VACCINE; DOUBLE-BLIND; RISK; EFFICACY;
IMMUNIZATION; INFECTION; TRIAL; STEP; H1N1
AB Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed. Published by Elsevier Ltd.
C1 [Chen, Robert T.; Carbery, Baevin; Mac, Lisa; Chapman, Louisa; Hendry, Michael] Ctr Dis Control & Prevent, DHAP, NCHHSTP, Atlanta, GA 30333 USA.
[Carbery, Baevin] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Berns, Kenneth I.; Condit, Richard C.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
[Excler, Jean-Louis] Int AIDS Vaccine Initiat, New York, NY USA.
US Mil HIV Res Program MHRP, Bethesda, MD 20817 USA.
[Gurwith, Marc] PaxVax, San Diego, CA 92121 USA.
[Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Khuri-Bulos, Najwa] Jordan Univ Hosp, Div Infect Dis, Amman, Jordan.
[Klug, Bettina] Paul Ehrlich Inst, D-63225 Langen, Germany.
[Robertson, James S.] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England.
[Seligman, Stephen J.] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA.
[Sheets, Rebecca] NIAID, Div Aids, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Williamson, Anna-Lise] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Williamson, Anna-Lise] Natl Hlth Lab Serv, Cape Town, South Africa.
RP Chen, RT (reprint author), Ctr Dis Control & Prevent, DHAP, NCHHSTP, 1600 Clifton Rd, Atlanta, GA 30333 USA.
EM brightoncollaborationv3swg@gmail.com
FU Intramural CDC HHS [CC999999]
NR 35
TC 5
Z9 5
U1 2
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JAN 1
PY 2015
VL 33
IS 1
BP 73
EP 75
DI 10.1016/j.vaccine.2014.09.035
PG 3
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AY6FX
UT WOS:000347663700013
PM 25305565
ER
PT J
AU Broadbent, AJ
Santos, CP
Paskel, M
Matsuoka, Y
Lu, JN
Chen, ZY
Jin, H
Subbarao, K
AF Broadbent, Andrew J.
Santos, Celia P.
Paskel, Myeisha
Matsuoka, Yumiko
Lu, Janine
Chen, Zhongying
Jin, Hong
Subbarao, Kanta
TI Replication of live attenuated cold-adapted H2N2 influenza virus vaccine
candidates in non human primates
SO VACCINE
LA English
DT Article
DE H2N2; Influenza; Vaccine; LAIV; Non-human primate; Monkey
ID ANN-ARBOR STRAIN; PROTECTIVE EFFICACY; AVIAN RESERVOIR; A VIRUSES;
IMMUNOGENICITY; INFECTION; FERRETS; AGE; IDENTIFICATION; SPECIFICITY
AB The development of an H2N2 vaccine is a priority in pandemic preparedness planning. We previously showed that a single dose of a cold-adapted (ca) H2N2 live attenuated influenza vaccine (LAIV) based on the influenza A/Ann Arbor/6/60 (AA ca) virus was immunogenic and efficacious in mice and ferrets. However, in a Phase I clinical trial, viral replication was restricted and immunogenicity was poor. In this study, we compared the replication of four H2N2 LAN candidate viruses, AA ca, A/Tecumseh/3/67 (TEC67 ca), and two variants of A/Japan/305/57 (JAP57 ca) in three non-human primate (NHP) species: African green monkeys (AGM), cynomolgus macaques (CM) and rhesus macaques (RM). One JAP57 CO virus had glutamine and glycine at HA amino acid positions 226 and 228 (Q-G) that binds to alpha 2-3 linked sialic acids, and one had leucine and serine that binds to alpha 2-3 and alpha-6 linked residues (L-S). The replication of all ca viruses was restricted, with low titers detected in the upper respiratory tract of all NHP species, however replication was detected in significantly more CMs than AGMs. The JAP57 ca Q-G and TEC67 ca viruses replicated in a significantly higher percentage of NHPs than the AA ca virus, with the TEC67 CO virus recovered from the greatest percentage of animals. Altering the receptor specificity of the JAP57 ca virus from alpha 2-3 to both alpha 2-3 and alpha 2-6 linked sialic acid residues did not significantly increase the number of animals infected or the titer to which the virus replicated. Taken together, our data show that in NHPs the AA ca virus more closely reflects the human experience than mice or ferret studies. We suggest that CMs and RMs may be the preferred species for evaluating H2N2 LAIV viruses, and the TEC67 ca virus may be the most promising H2N2 LAIV candidate for further evaluation. Published by Elsevier Ltd.
C1 [Broadbent, Andrew J.; Santos, Celia P.; Paskel, Myeisha; Matsuoka, Yumiko; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Lu, Janine; Chen, Zhongying; Jin, Hong] MedImmune LLC, Mountain View, CA USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Room 3E13C-1,Bldg 33,33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
OI Broadbent, Andrew/0000-0002-4716-1835
FU Intramural Research Program of the National Institutes of Health (NIH);
National Institute of Allergy and Infectious Diseases (NIAID)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH) and the National Institute of
Allergy and Infectious Diseases (NIAID). The pandemic influenza vaccine
program is part of a Cooperative Research and Development Agreement
between the Laboratory of Infectious Diseases, NIAID and MedImmune. We
would like to thank Dr. Arnold Monto for providing the sample from which
the Tec67 HA and NA were amplified and Dr. Richard Herbert, Joanne
Swerczek, Mark Szarowicz and the staff of the NIH Animal Center at
Poolesville for technical support in the animal studies.
NR 34
TC 1
Z9 2
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JAN 1
PY 2015
VL 33
IS 1
BP 193
EP 200
DI 10.1016/j.vaccine.2014.10.065
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA AY6FX
UT WOS:000347663700030
PM 25444799
ER
PT J
AU Shapiro, SZ
AF Shapiro, Stuart Z.
TI A Proposal to Use Iterative, Small Clinical Trials to Optimize
Therapeutic HIV Vaccine Immunogens to Launch Therapeutic HIV Vaccine
Development
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID T-CELL RESPONSE; INFECTION; DIVERSITY; ESCAPE
AB The HIV cure agenda has rekindled interest in the development of a therapeutic HIV vaccine. An iterative clinical trial strategy that proved successful for the development of effective cancer chemotherapies in the 1960s may be applicable to the development of a CD8 T lymphocyte-based therapeutic HIV vaccine. However, while cancer chemotherapy development could begin with iterative clinical trials to improve the use of active drugs, the first step in therapeutic HIV vaccine design should be discovery of immunogen constructs with potential for activity and their optimization to meet the challenges of HIV-1 sequence diversity and human polymorphism in T cell antigen presentation. A strategy for doing this is discussed in this article. The proposed strategy relies on a major commitment by funding organizations to fund organized and coordinated manufacture and clinical testing of a series of first- and second-generation constructs to test basic concepts in product design. This is presented as an alternative to funding a more traditional competition among private manufacturers and product champions of individual, already designed products.
C1 NIAID, Vaccine Res Program, Div Aids, Bethesda, MD 20892 USA.
RP Shapiro, SZ (reprint author), NIAID, Vaccine Res Program, Div Aids, 5601 Fishers Lane,Room 9C20B, Bethesda, MD 20892 USA.
EM sshapiro@niaid.nih.gov
NR 22
TC 0
Z9 0
U1 1
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JAN 1
PY 2015
VL 31
IS 1
SI SI
BP 49
EP 55
DI 10.1089/aid.2014.0172
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AY8DO
UT WOS:000347784900009
PM 25286142
ER
PT J
AU Moniuszko, M
Liyanage, NPM
Doster, MN
Parks, RW
Grubczak, K
Lipinska, D
McKinnon, K
Brown, C
Hirsch, V
Vaccari, M
Gordon, S
Pegu, P
Fenizia, C
Flisiak, R
Grzeszczuk, A
Dabrowska, M
Robert-Guroff, M
Silvestri, G
Stevenson, M
McCune, J
Franchini, G
AF Moniuszko, Marcin
Liyanage, Namal P. M.
Doster, Melvin N.
Parks, Robyn Washington
Grubczak, Kamil
Lipinska, Danuta
McKinnon, Katherine
Brown, Charles
Hirsch, Vanessa
Vaccari, Monica
Gordon, Shari
Pegu, Poonam
Fenizia, Claudio
Flisiak, Robert
Grzeszczuk, Anna
Dabrowska, Milena
Robert-Guroff, Marjorie
Silvestri, Guido
Stevenson, Mario
McCune, Joseph
Franchini, Genoveffa
TI Glucocorticoid Treatment at Moderate Doses of SIVmac251-Infected Rhesus
Macaques Decreases the Frequency of Circulating CD14(+)CD16(++)
Monocytes But Does Not Alter the Tissue Virus Reservoir
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; PREFERENTIALLY HARBORS HIV-1; INNATE
IMMUNE ACTIVATION; CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS;
SIMIAN-IMMUNODEFICIENCY; INFECTED PATIENTS; BLOOD MONOCYTES; IN-VIVO;
SUBSET
AB Subsets of CD16-positive monocytes produce proinflammatory cytokines and expand during chronic infection with the human immunodeficiency virus type 1 (HIV). HIV-infected macrophage in tissues may be long lived and contribute to the establishment and maintenance of the HIV reservoir. We found that the (intermediate) CD14(++)CD16(+) and (nonclassical) CD14(+)CD16(++) monocyte subsets are significantly expanded during infection of Rhesus macaques with pathogenic SIVmac251 but not during infection of sooty mangabeys with the nonpathogenic isolate SIVSM. In vitro glucocorticoid (GC) treatment of peripheral blood mononuclear cells (PBMCs) from uninfected or SIVmac251-infected Rhesus macaques and HIV-infected patients treated or not with antiretroviral therapy (ART) resulted in a significant decrease in the frequency of both CD16-positive monocyte subsets. Short-term in vivo treatment with high doses of GC of chronically SIVmac251-infected macaques resulted in a significant decrease in the CD14(+)CD16(++) population and, to a lesser extent, in the CD14(++)CD16(+) monocytes, as well as a significant decrease in the number of macrophages in tissues. Surprisingly, treatment of SIVmac251-infected macaques with ART significantly increased the CD14(++)CD16(+) population and the addition of GC resulted in a significant decrease in only the CD14(+)CD16(++) subset. No difference in SIV DNA levels in blood, lymph nodes, gut, and spleen was found between the groups treated with ART or ART plus GC. Thus, it appears that high doses of GC treatment in the absence of ART could affect both CD16-positive populations in vivo. Whether the efficacy of this treatment at higher doses to decrease virus levels outweighs its risks remains to be determined.
C1 [Moniuszko, Marcin; Grubczak, Kamil] Med Univ Bialystok, Dept Allergol & Internal Med, Bialystok, Poland.
[Moniuszko, Marcin] Med Univ Bialystok, Dept Regenerat Med & Immune Regulat, Bialystok, Poland.
[Liyanage, Namal P. M.; Doster, Melvin N.; Parks, Robyn Washington; Vaccari, Monica; Gordon, Shari; Pegu, Poonam; Fenizia, Claudio; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA.
[Lipinska, Danuta] Med Univ Bialystok, Dept Endocrinol Diabetol & Internal Med, Bialystok, Poland.
[McKinnon, Katherine] NCI, FACS Core Facil, NIH, Bethesda, MD 20892 USA.
[Brown, Charles; Hirsch, Vanessa] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Flisiak, Robert; Grzeszczuk, Anna] Med Univ Bialystok, Dept Infect Dis & Hepatol, Bialystok, Poland.
[Dabrowska, Milena] Med Univ Bialystok, Dept Hematol Diagnost, Bialystok, Poland.
[Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Silvestri, Guido] Emory Univ, Atlanta, GA 30322 USA.
[Stevenson, Mario] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[McCune, Joseph] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94143 USA.
RP Franchini, G (reprint author), NCI, NIH, Bldg 41,Room D-804, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research, DARE
collaboratory Grant from NIAID [P30AI073961]; Polish National Science
Center [NN401530240]; [R37A1-6698]; [PS10D1107]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, DARE
collaboratory Grant P30AI073961 from NIAID, grant R37A1-6698 to Guido
Silvestri and Grant PS10D1107 to Yerkes National Primate Research
center. We thank Teresa Habina for editorial assistance, Hue Chung and
Ranajit Pal for the viral SIV DNA measurement, and Dr. Alan Landay for
useful discussions. Marcin Moniuszko was supported by a grant from the
Polish National Science Center (NN401530240). FTC and PMPA was a
generous gift from Gilead Science, Inc. and Raltegrevir was a generous
gift from Merck and Co.
NR 44
TC 5
Z9 5
U1 1
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JAN 1
PY 2015
VL 31
IS 1
SI SI
BP 115
EP 126
DI 10.1089/aid.2013.0220
PG 12
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AY8DO
UT WOS:000347784900017
PM 24432835
ER
PT J
AU Zanussi, S
Bortolin, MT
Pratesi, C
Tedeschi, R
Basaglia, G
Abbruzzese, L
Mazzucato, M
Spina, M
Vaccher, E
Tirelli, U
Rupolo, M
Michieli, M
Di Mascio, M
De Paoli, P
AF Zanussi, Stefania
Bortolin, Maria Teresa
Pratesi, Chiara
Tedeschi, Rosamaria
Basaglia, Giancarlo
Abbruzzese, Luciano
Mazzucato, Mario
Spina, Michele
Vaccher, Emanuela
Tirelli, Umberto
Rupolo, Maurizio
Michieli, Mariagrazia
Di Mascio, Michele
De Paoli, Paolo
TI Autograft HIV-DNA Load Predicts HIV-1 Peripheral Reservoir After Stem
Cell Transplantation for AIDS-Related Lymphoma Patients
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HEMATOPOIETIC PROGENITOR CELLS; CD4 T-CELLS; ANTIRETROVIRAL THERAPY;
BONE-MARROW; IMMUNE RECONSTITUTION; UNDIFFERENTIATED CARCINOMA;
NASOPHARYNGEAL TYPE; INFECTION; PERSISTENCE; LYMPHOCYTES
AB Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/10(6) peripheral blood mononuclear cells (PBMCs), range 13-479, p=0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R-2=0.84, p=0.01) to month 12 follow-up (R-2=0.99, p=0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.
C1 [Zanussi, Stefania; Bortolin, Maria Teresa; Pratesi, Chiara; Tedeschi, Rosamaria; Basaglia, Giancarlo] CRO Natl Canc Inst, Microbiol Immunol & Virol Unit, I-33081 Aviano, PN, Italy.
[Abbruzzese, Luciano; Mazzucato, Mario] CRO Natl Canc Inst, Stem Cell Collect & Proc Unit, I-33081 Aviano, PN, Italy.
[Spina, Michele; Vaccher, Emanuela; Tirelli, Umberto] CRO Natl Canc Inst, Div Med Oncol A, I-33081 Aviano, PN, Italy.
[Rupolo, Maurizio; Michieli, Mariagrazia] CRO Natl Canc Inst, Cellular Therapy & High Dose Chemotherapy Unit, I-33081 Aviano, PN, Italy.
[Di Mascio, Michele] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[De Paoli, Paolo] CRO Natl Canc Inst, Sci Directorate, I-33081 Aviano, PN, Italy.
RP Zanussi, S (reprint author), CRO Natl Canc Inst, Microbiol Immunol & Virol Unit, Via F Gallini 2, I-33081 Aviano, PN, Italy.
EM szanussi@cro.it
OI Bortolin, Maria Teresa/0000-0003-0589-1669; Mazzucato,
Mario/0000-0001-8319-053X; De Paoli, Paolo/0000-0002-9502-1781
FU Ministero del lavoro, della salute e delle politiche sociali [40H73]
FX We thank Luigina Mei for editorial assistance. This work was supported
by grants from "Ministero del lavoro, della salute e delle politiche
sociali" (grant 40H73). The content of this article has been presented
as an oral communication to the VI Italian Conference on AIDS and
Retroviruses, Rome, May 25-27, 2014.
NR 47
TC 4
Z9 5
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JAN 1
PY 2015
VL 31
IS 1
SI SI
BP 150
EP 159
DI 10.1089/aid.2014.0157
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AY8DO
UT WOS:000347784900021
PM 25581618
ER
PT J
AU Choi, HW
Kim, HR
Baek, HJ
Kook, H
Cho, D
Shin, JH
Suh, SP
Ryang, DW
Shin, MG
AF Choi, Hyun-Woo
Kim, Hye-Ran
Baek, Hee-Jo
Kook, Hoon
Cho, Duck
Shin, Jong-Hee
Suh, Soon-Pal
Ryang, Dong-Wook
Shin, Myung-Geun
TI Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1,
and SRSF2 in Childhood Acute Myeloid Leukemia
SO ANNALS OF LABORATORY MEDICINE
LA English
DT Article
DE SETBP1; SF3B1; U2AF1; SRSF2; AML; Childhood
ID MUTATIONS; MACHINERY; MYELODYSPLASIA; MANAGEMENT; PREDICTS; IDH1
AB Background: Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBPI, splicing factor 31 subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor I (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML.
Methods: Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBPI, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients.
Results: Childhood AML patients did not harbor any recurrent SETBPI gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients.
Conclusions: Alterations of the SETBPI gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood.
C1 [Choi, Hyun-Woo; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Dept Lab Med, Hwasun 519763, South Korea.
[Kim, Hye-Ran; Shin, Myung-Geun] Chonnam Natl Univ, Sch Med, Brain Korea Plus Project 21, Kwangju, South Korea.
[Kim, Hye-Ran] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Baek, Hee-Jo; Kook, Hoon] Chonnam Natl Univ, Hwasun Hosp, Dept Pediat, Hwasun 519763, South Korea.
[Baek, Hee-Jo; Kook, Hoon; Shin, Myung-Geun] Chonnam Natl Univ, Hwasun Hosp, Environm Hlth Ctr Childhood Leukemia & Canc, Hwasun 519763, South Korea.
RP Shin, MG (reprint author), Chonnam Natl Univ, Sch Med, Dept Lab Med, 322 Seoyang Ro, Hwasun 519763, South Korea.
EM mgshin@chonnam.ac.kr
FU National Research Foundation of Korea (NRF) [2011-0015304]; NRF Basic
Science Research Program [2010-0024326]; Leading Foreign Research
Institute Recruitment Program through the NRF - Ministry of Education,
Science and Technology (MEST) [20110030034]; National R&D Program for
Cancer Control, Ministry of Health & Welfare, Republic of Korea
[2013-1320070]
FX This study was supported by the National Research Foundation of Korea
(NRF) and grants (No. 2011-0015304), the NRF Basic Science Research
Program (grant 2010-0024326), the Leading Foreign Research Institute
Recruitment Program (No. 20110030034) through the NRF funded by the
Ministry of Education, Science and Technology (MEST), and a grant from
the National R&D Program for Cancer Control, Ministry of Health &
Welfare, Republic of Korea (No. 2013-1320070).
NR 21
TC 0
Z9 0
U1 1
U2 4
PU KOREAN SOC LABORATORY MEDICINE
PI SEOUL
PA KOREAN MEDICAL ASSOC BLDG, RM 602,302-75 ICHON 1-DONG, YONGSAN-GU,
SEOUL, 140-721, SOUTH KOREA
SN 2234-3806
EI 2234-3814
J9 ANN LAB MED
JI Ann. Lab. Med.
PD JAN
PY 2015
VL 35
IS 1
BP 118
EP 122
DI 10.3343/alm.2015.35.1.118
PG 5
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA AY7MW
UT WOS:000347745100018
PM 25553291
ER
PT J
AU Krenz, JE
Hofmann, JN
Smith, TR
Cunningham, RN
Fenske, RA
Simpson, CD
Keifer, M
AF Krenz, Jennifer E.
Hofmann, Jonathan N.
Smith, Theresa R.
Cunningham, Rad N.
Fenske, Richard A.
Simpson, Christopher D.
Keifer, Matthew
TI Determinants of Butyrylcholinesterase Inhibition Among Agricultural
Pesticide Handlers in Washington State: An Update
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE agriculture; biological monitoring; cholinesterase; determinants of
exposure; occupational exposure; organophosphorus compounds; pesticide;
pesticide handler
ID ORGANOPHOSPHATE PESTICIDES; ACETYLCHOLINESTERASE ACTIVITY; PRENATAL
EXPOSURE; WORKERS; HEALTH; CHOLINESTERASE; CHLORPYRIFOS; BIOMARKER;
CHILDREN; PLASMA
AB Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are used widely in agriculture to manage insect pests of economic importance. Agricultural workers are more likely to suffer exposure because of the widespread use of OP/CBs in agriculture, and pesticide-related illnesses among handlers may be more severe when compared to other farm workers. The goal of this study was to identify occupational and personal characteristics associated with butyrylcholinesterase (BuChE) inhibition in participants recruited from the Washington State Cholinesterase Monitoring Program from 2006 to 2011.
We conducted a longitudinal study among agricultural pesticide handlers in Washington State during the OP/CB spray season (March-July) over a 6-year period (2006-2011). Linear mixed effects regression models were used to evaluate BuChE inhibition in relation to self-reported occupational and personal characteristics.
Relative to pre-season baseline levels, the mean decrease in BuChE activity during the OP/CB spray season over all years of the study period was 3.77% (P < 0.001). Greater BuChE inhibition was observed among handlers who reported using multiple OP/CBs (beta = -2.70, P = 0.045), mixed or loaded OP/CBs (beta = -3.97, P = 0.002), did not store personal protective equipment (PPE) in a locker at work (beta = -3.4, P = 0.014), or did not wear chemical-resistant boots (beta = -16.6, P < 0.001).
The Washington State Cholinesterase Monitoring Program has provided a valuable opportunity to evaluate potential sources of OP/CB exposure among agricultural pesticide handlers. Several previously reported associations were confirmed in the current analysis, which included a larger number of pesticide handlers enrolled over a longer time period. The use of multiple OP/CBs and mixing/loading activities were significant risk factors, and the use of chemical-resistant boots and lockers for PPE storage were protective factors. Our findings point toward logical interventions to reduce exposure such as the implementation of engineering controls for mixing/loading activities, requirements for appropriate footwear, and the regular use of lockers for PPE storage.
C1 [Krenz, Jennifer E.; Cunningham, Rad N.; Fenske, Richard A.; Simpson, Christopher D.] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
[Hofmann, Jonathan N.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Smith, Theresa R.] Univ Washington, Dept Stat, Seattle, WA 98195 USA.
[Keifer, Matthew] Marshfield Clin Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA.
RP Simpson, CD (reprint author), Univ Washington, Dept Environm & Occupat Hlth Sci, Box 357234, Seattle, WA 98195 USA.
EM simpson1@uw.edu
FU United States Centers for Disease Control, National Institute of
Occupational Safety and health (CDC/NIOSH) [2 U50 OH07544-07, 1 T42
OH008433-01]; United States National Institute of Environmental Health
Sciences (NIEHS) [P30 ES07033, P42 ES04696-22, T32 ES07262]
FX United States Centers for Disease Control, National Institute of
Occupational Safety and health (CDC/NIOSH) (2 U50 OH07544-07, 1 T42
OH008433-01); United States National Institute of Environmental Health
Sciences (NIEHS) (P30 ES07033, P42 ES04696-22, T32 ES07262).
NR 41
TC 2
Z9 2
U1 2
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
EI 1475-3162
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JAN
PY 2015
VL 59
IS 1
BP 25
EP 40
DI 10.1093/annhyg/meu072
PG 16
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA AY8ZS
UT WOS:000347839800004
PM 25261454
ER
PT J
AU Friesen, MC
Locke, SJ
Chen, YC
Coble, JB
Stewart, PA
Ji, BT
Bassig, B
Lu, W
Xue, SZ
Chow, WH
Lan, Q
Purdue, MP
Rothman, N
Vermeulen, R
AF Friesen, Melissa C.
Locke, Sarah J.
Chen, Yu-Cheng
Coble, Joseph B.
Stewart, Patricia A.
Ji, Bu-Tian
Bassig, Bryan
Lu, Wei
Xue, Shouzheng
Chow, Wong-Ho
Lan, Qing
Purdue, Mark P.
Rothman, Nathaniel
Vermeulen, Roel
TI Historical Occupational Trichloroethylene Air Concentrations Based on
Inspection Measurements From Shanghai, China
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE China; occupational exposures; population-based studies; statistical
model; trichloroethylene
ID JOB-EXPOSURE MATRIX; LONG-TERM TRENDS; HYPERSENSITIVITY DERMATITIS;
COMPREHENSIVE EVALUATION; PERCHLOROETHYLENE; EPIDEMIOLOGY; INDUSTRY;
WORKERS; HEALTH; COHORT
AB Trichloroethylene (TCE) is a carcinogen that has been linked to kidney cancer and possibly other cancer sites including non-Hodgkin lymphoma. Its use in China has increased since the early 1990s with China's growing metal, electronic, and telecommunications industries. We examined historical occupational TCE air concentration patterns in a database of TCE inspection measurements collected in Shanghai, China to identify temporal trends and broad contrasts among occupations and industries.
Using a database of 932 short-term, area TCE air inspection measurements collected in Shanghai worksites from 1968 through 2000 (median year 1986), we developed mixed-effects models to evaluate job-, industry-, and time-specific TCE air concentrations.
Models of TCE air concentrations from Shanghai work sites predicted that exposures decreased 5-10% per year between 1968 and 2000. Measurements collected near launderers and dry cleaners had the highest predicted geometric means (GM for 1986 = 150-190mg m(-3)). The majority (53%) of the measurements were collected in metal treatment jobs. In a model restricted to measurements in metal treatment jobs, predicted GMs for 1986 varied 35-fold across industries, from 11mg m(-3) in 'other metal products/repair' industries to 390mg m(-3) in 'ships/aircrafts' industries.
TCE workplace air concentrations appeared to have dropped over time in Shanghai, China between 1968 and 2000. Understanding differences in TCE concentrations across time, occupations, and industries may assist future epidemiologic studies in China.
C1 [Friesen, Melissa C.; Locke, Sarah J.; Chen, Yu-Cheng; Coble, Joseph B.; Stewart, Patricia A.; Ji, Bu-Tian; Bassig, Bryan; Xue, Shouzheng; Chow, Wong-Ho; Lan, Qing; Purdue, Mark P.; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA 22207 USA.
[Lu, Wei] Shanghai Municipal Ctr Dis Control, Shanghai, Peoples R China.
[Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, Utrecht, Netherlands.
RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Purdue, Mark/C-9228-2016; Friesen, Melissa/A-5362-2009; Vermeulen,
Roel/F-8037-2011
OI Purdue, Mark/0000-0003-1177-3108; Vermeulen, Roel/0000-0003-4082-8163
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health [Z01
CP10122-19]
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health (Z01
CP10122-19).
NR 33
TC 0
Z9 0
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
EI 1475-3162
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JAN
PY 2015
VL 59
IS 1
BP 62
EP 78
DI 10.1093/annhyg/meu066
PG 17
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA AY8ZS
UT WOS:000347839800007
PM 25180291
ER
PT J
AU Cuzick, J
Thorat, MA
Bosetti, C
Brown, PH
Burn, J
Cook, NR
Ford, LG
Jacobs, EJ
Jankowski, JA
La Vecchia, C
Law, M
Meyskens, F
Rothwell, PM
Senn, HJ
Umar, A
AF Cuzick, J.
Thorat, M. A.
Bosetti, C.
Brown, P. H.
Burn, J.
Cook, N. R.
Ford, L. G.
Jacobs, E. J.
Jankowski, J. A.
La Vecchia, C.
Law, M.
Meyskens, F.
Rothwell, P. M.
Senn, H. J.
Umar, A.
TI Estimates of benefits and harms of prophylactic use of aspirin in the
general population
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE aspirin; prevention; benefit-harm; cancer; cardiovascular disease;
gastrointestinal bleeding
ID LOW-DOSE ASPIRIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED
CONTROLLED-TRIALS; PEPTIC-ULCER DISEASE; HELICOBACTER-PYLORI; PRIMARY
PREVENTION; COLORECTAL-CANCER; COST-EFFECTIVENESS; HEART-DISEASE;
FOLLOW-UP
AB .Accumulating evidence supports an effect of aspirin in reducing overall cancer incidence and mortality in the general population. We reviewed current data and assessed the benefits and harms of prophylactic use of aspirin in the general population.
The effect of aspirin for site-specific cancer incidence and mortality, cardiovascular events was collated from the most recent systematic reviews. Studies identified through systematic Medline search provided data regarding harmful effects of aspirin and baseline rates of harms like gastrointestinal bleeding and peptic ulcer.
The effects of aspirin on cancer are not apparent until at least 3 years after the start of use, and some benefits are sustained for several years after cessation in long-term users. No differences between low and standard doses of aspirin are observed, but there were no direct comparisons. Higher doses do not appear to confer additional benefit but increase toxicities. Excess bleeding is the most important harm associated with aspirin use, and its risk and fatality rate increases with age. For average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period.
Prophylactic aspirin use for a minimum of 5 years at doses between 75 and 325 mg/day appears to have favourable benefit-harm profile; longer use is likely to have greater benefits. Further research is needed to determine the optimum dose and duration of use, to identify individuals at increased risk of bleeding, and to test effectiveness of Helicobacter pylori screening-eradication before starting aspirin prophylaxis.
C1 [Cuzick, J.; Thorat, M. A.] Queen Mary Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, London EC1M 6BQ, England.
[Bosetti, C.; La Vecchia, C.] IRCCS Ist Ric Farmacol Mario Negri, Dept Epidemiol, Milan, Italy.
[Brown, P. H.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Burn, J.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Cook, N. R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
[Ford, L. G.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Jacobs, E. J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Jankowski, J. A.] Univ Plymouth, Ctr Biomed Res Translat & Stratified Med, Peninsula Sch Med, Plymouth PL4 8AA, Devon, England.
[Jankowski, J. A.] Univ Plymouth, Ctr Biomed Res Translat & Stratified Med, Peninsula Sch Dent, Plymouth PL4 8AA, Devon, England.
[Jankowski, J. A.] Queen Mary Univ London, Blizard Inst Cell & Mol Sci, Ctr Digest Dis, London, England.
[La Vecchia, C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Law, M.] Queen Mary Univ London, Ctr Environm & Prevent Med, Wolfson Inst Prevent Med, London EC1M 6BQ, England.
[Meyskens, F.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA.
[Rothwell, P. M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford, England.
[Senn, H. J.] Tumor & Breast Ctr ZeTuP, St Gallen, Switzerland.
[Umar, A.] NCI, Gastrointestinal & Other Cancers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Cuzick, J (reprint author), Queen Mary Univ London, Ctr Canc Prevent, Wolfson Inst Prevent Med, Charterhouse Sq, London EC1M 6BQ, England.
EM j.cuzick@qmul.ac.uk
RI Jankowski, Janusz/H-2706-2012; Thorat, Mangesh/A-9787-2008;
OI Jankowski, Janusz/0000-0003-2130-9181; Thorat,
Mangesh/0000-0001-8673-5320; La Vecchia, Carlo/0000-0003-1441-897X;
Burn, John/0000-0002-9823-2322
FU International Society of Cancer Prevention (ISCaP); Cancer Research UK
(CRUK); British Heart Foundation (BHF); American Cancer Society (ACS);
CRUK; BHF; ACS
FX This evidence review meeting was sponsored by International Society of
Cancer Prevention (ISCaP), Cancer Research UK (CRUK), British Heart
Foundation (BHF) and American Cancer Society (ACS) and received funding
from CRUK, BHF and ACS. Sponsors and funding sources had no role in
study design, data collection and analysis, decision to publish or
preparation of the manuscript.
NR 52
TC 80
Z9 83
U1 7
U2 30
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JAN
PY 2015
VL 26
IS 1
BP 47
EP 57
DI 10.1093/annonc/mdu225
PG 11
WC Oncology
SC Oncology
GA AY2JP
UT WOS:000347416300008
PM 25096604
ER
PT J
AU Qiang, W
Yau, WM
Schulte, J
AF Qiang, Wei
Yau, Wai-Ming
Schulte, Juergen
TI Fibrillation of beta amyloid peptides in the presence of phospholipid
bilayers and the consequent membrane disruption
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE Alzheimer's disease; Neurotoxicity mechanism; Membrane disruption;
amyloid fibril; Solid state NMR
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; SYNAPTIC PLASMA-MEMBRANES;
HIV FUSION PEPTIDE; ALZHEIMERS-DISEASE; A-BETA; LIPID-MEMBRANES;
PRECURSOR PROTEIN; THIOFLAVIN-T; METAL-IONS
AB Fibrillation of beta amyloid (A beta) peptides and the accumulation of amyloid plaques are considered as an important clinical hallmark to identify Alzheimer's disease (AD). The physiological connection between A beta plaques and the disruption of neuronal cells has not been clearly understood. One hypothesis to explain the A beta neurotoxicity is that the fibrillation process induces disruption to the cellular membrane. We studied the A beta fibrillation process in two biologically relevant conditions with the peptide either pre-incorporated into or externally added to the synthetic phospholipid bilayers. These two sample preparation conditions mimic the physiological membrane proximities of A beta peptides before and after the enzymatic cleavage of amyloid precursor protein (APP). Using thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM), we were able to monitor the kinetics and morphological evolution of fibril formation, which was highly sensitive to the two sample preparation protocols. While the external addition protocol generates long and mature fibrils through normal fibrillation process, the pre-incubation protocol was found to stabilize the immature protofibrils. Fluorescence spectroscopy studies with doubly-labeled phospholipids indicated that there may be a lipid uptake process associated with the fibril formation. Solid state nuclear magnetic resonance (NMR) spectroscopy provided evidence for high resolution structural variations in fibrils formed with different protocols, and in particular the stabilization of long-range contact between N- and C-terminal beta strands. In addition, disruption of phospholipid bilayers was supported by measurements with P-31 chemical shifts and relaxation time constants. This article is part of a Special Issue entitled: NMR Spectroscopy for Atomistic Views of Biomembranes and Cell Surfaces. Guest Editors: Lynette Cegelski and David P. Weliky. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Qiang, Wei; Schulte, Juergen] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
[Qiang, Wei; Yau, Wai-Ming] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Qiang, W (reprint author), SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
EM wqiang@binghamton.edu
FU National Institutes of Health; Binghamton University, State University
of New York; NSF Major Research Instrumentation Program [NSF 0922815]
FX This work was supported by the intramural research program at the
National Institutes of Health and the startup research funding from
Binghamton University, State University of New York. The NMR experiments
on the 600 MHz spectrometer were funded by the NSF Major Research
Instrumentation Program (NSF 0922815). We greatly thank Dr. Robert Tycko
for his support on using materials and instruments, as well as helpful
discussion of the results.
NR 72
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U1 7
U2 57
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD JAN
PY 2015
VL 1848
IS 1
SI SI
BP 266
EP 276
DI 10.1016/j.bbamem.2014.04.011
PN B
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA AY7NQ
UT WOS:000347747100008
PM 24769158
ER
PT J
AU Huynh, N
Beutler, JA
Shulkes, A
Baldwin, GS
He, H
AF Nhi Huynh
Beutler, John A.
Shulkes, Arthur
Baldwin, Graham S.
He, Hong
TI Glaucarubinone inhibits colorectal cancer growth by suppression of
hypoxia-inducible factor 1 alpha and beta-catenin via a p-21 activated
kinase 1-dependent pathway
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Glaucarubinone; PAK1; HIF-1 alpha; beta-Catenin; CRC
ID P21-ACTIVATED KINASES; PROTEIN-SYNTHESIS; QUASSINOIDS; CELLS;
FACTOR-1-ALPHA; SURVIVAL; APC
AB p-21-Activated kinase 1 (PAK1) enhances colorectal cancer (CRC) progression by stimulating Wnt/beta-catenin, ERK and AKT pathways. PAK1 also promotes CRC survival via up-regulation of hypoxia-inducible factor 1 alpha (HIF-1 alpha), a key player in cancer survival. Glaucarubinone, a quassinoid natural product, inhibits pancreatic cancer growth by down-regulation of PAK1. The aim of this study was to investigate the effect of glaucarubinone on CRC growth and metastasis, and the mechanism involved. Cell proliferation was measured in vitro by [H-3]-thymidine incorporation and in vivo by volume of tumor xenografts. Protein concentrations were measured by Western blotting of cell extracts. We report here that glaucarubinone inhibited CRC growth both in vitro and in vivo. The potency of glaucarubinone as an inhibitor of cell proliferation was negatively correlated to PAK1 expression in CRC cells. Glaucarubinone suppressed the expression of HIF-1 alpha and beta-catenin. Knockdown of PAK1 by shRNA enhanced inhibition by glaucarubinone while constitutively active PAK1 blocked the inhibitory effect. Our findings indicate that glaucarubinone inhibited CRC growth by down-regulation of HIF-1 alpha or. and beta-catenin via a PAK1-dependent pathway. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Nhi Huynh; Shulkes, Arthur; Baldwin, Graham S.; He, Hong] Univ Melbourne, Austin Hlth, Dept Surg, Heidelberg, Vic 3084, Australia.
[Beutler, John A.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP He, H (reprint author), Univ Melbourne, Austin Hlth, Dept Surg, Studley Rd, Heidelberg, Vic 3084, Australia.
EM hong.he@unimelb.edu.au
OI Baldwin, Graham/0000-0002-0944-8747
FU National Health and Medical Research Council (NHMRC) of Australia
[508908, 1041831]; Austin Hospital Medical Research Foundation [2-1281];
Intramural Research Program of the NIH National Cancer Institute Center
for Cancer Research [1 ZIA BC011470 02]
FX This work was supported by the National Health and Medical Research
Council (NHMRC) of Australia grants 508908 (HH) and 1041831 (GB & AS),
by the Austin Hospital Medical Research Foundation 2-1281 (HH), and by
the Intramural Research Program of the NIH National Cancer Institute
Center for Cancer Research 1 ZIA BC011470 02 (JB).
NR 32
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U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JAN
PY 2015
VL 1853
IS 1
BP 157
EP 165
DI 10.1016/j.bbamcr.2014.10.013
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AY5FJ
UT WOS:000347598100015
PM 25409929
ER
PT J
AU Song, CC
Wang, Q
Song, CZ
Lockett, SJ
Colburn, NH
Li, CCH
Wang, JM
Rogers, TJ
AF Song, Changcheng
Wang, Qing
Song, Changzheng
Lockett, Stephen J.
Colburn, Nancy H.
Li, Chou-Chi H.
Wang, Ji Ming
Rogers, Thomas J.
TI Nucleocytoplasmic shuttling of valosin-containing protein (VCP/p97)
regulated by its N domain and C-terminal region
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Article
DE Valosin containing protein; Nucleocytoplasmic shuttling; Nuclear export
signal; Inclusion body myopathy associated with Paget's disease of bone
and frontotemporal dementia (IBMPFD)
ID AAA-ATPASE P97/VCP; NUCLEAR EXPORT SIGNAL; P97/VALOSIN-CONTAINING
PROTEIN; FRONTOTEMPORAL DEMENTIA; PAGET-DISEASE; D1 RING; NUCLEOLAR;
P97; LOCALIZATION; P97-VCP
AB Valosin-containing protein (VCP or p97), a member of the AAA family (ATPases associated with diverse cellular activities), plays a key role in many important cellular activities. A genetic deficiency of VCP can cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). Previous studies showed that the VCP N domain is essential for the regulation of nuclear entry of VCP. Here we report that IBMPFD mutations, which are mainly located in the N domain, suppress the nuclear entry of VCP. Moreover, the peptide sequence G(780)AGPSQ in the C-terminal region regulates the retention of VCP in the nucleus. A mutant lacking this sequence can increase the nuclear distribution of IBMPFD VCP, suggesting that this sequence is a potential molecular target for correcting the deficient nucleocytoplasmic shuttling of IBMPFD VCP proteins. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Song, Changcheng; Rogers, Thomas J.] Temple Univ, Ctr Inflammat Translat & Clin Res, Sch Med, Philadelphia, PA 19140 USA.
[Wang, Ji Ming] NCI, Ctr Canc Res, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Lockett, Stephen J.] NCI, Opt Microscopy & Anal Lab, Adv Technol Program, Frederick, MD 21702 USA.
[Colburn, Nancy H.; Li, Chou-Chi H.] NCI, Lab Canc Prevent, Frederick, MD 21702 USA.
[Li, Chou-Chi H.] NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA.
[Song, Changzheng] Shandong Acad Med Sci, Erythrocrine Project Translat Med, Jinan 250062, Peoples R China.
[Wang, Qing] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA.
RP Song, CC (reprint author), Temple Univ, Ctr Inflammat Translat & Clin Res, Sch Med, MERB 1183H,3500 N Broad St, Philadelphia, PA 19140 USA.
EM songc@temple.edu
FU NIEHS [1R21ES023051]; NCI [NO1CO56000, HHSN261200800001E]; Intramural
Research Program of the NIH National Cancer Institute Center for Cancer
Research [N01-CO-12400]; National Natural Science Foundation of China
[30672433, 30271215]; Natural Science Foundation of Shandong Province
[1872010ZRE27212]
FX We thank Drs. Carlos Barrero, Ying Wang and Ren-Ming Dai for technical
support, and Dr. Madesh Muniswamy for providing the confocal imaging
facility. The content of this publication does not necessarily reflect
the views or policies of the Department of Health and Human Services nor
does mention of trade names, commercial products, or organizations imply
endorsement by the US Government. The publisher or recipient
acknowledges the right of the US Government to retain a nonexclusive,
royalty-free license in and to any copyright covering the manuscript.
This research was funded by NIEHS 1R21ES023051 for C.S. Other supports
include: DA-14230, DA-25532, and DA-13429 for T.J.R.; NCI Contract Nos.
NO1CO56000 and HHSN261200800001E for S.L.; Intramural Research Program
of the NIH National Cancer Institute Center for Cancer Research under
contract N01-CO-12400 for N.C., C.C.L. and J.M.W.; National Natural
Science Foundation of China Nos. 30672433 and 30271215 and Natural
Science Foundation of Shandong Province No. 1872010ZRE27212 for S.C.Z.
NR 31
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U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JAN
PY 2015
VL 1853
IS 1
BP 222
EP 232
DI 10.1016/j.bbamcr.2014.10.019
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AY5FJ
UT WOS:000347598100021
PM 25447673
ER
PT J
AU Zhao, HB
Peddada, SD
Cui, XP
AF Zhao, Haibing
Peddada, Shyamal D.
Cui, Xinping
TI Mixed directional false discovery rate control in multiple pairwise
comparisons using weighted p-values
SO BIOMETRICAL JOURNAL
LA English
DT Article; Proceedings Paper
CT 8th International Conference on Multiple Comparison Procedures (MCP2013)
CY JUL 08-11, 2013
CL Univ Southampton, Southampton, UNITED KINGDOM
HO Univ Southampton
DE Benjamini Hochberg procedure; Microarray; Mixed directional false
discovery rate; Multiple pairwise comparison; Weighted p-value
ID LIVER-CANCER; ACETAMINOPHEN; PROPORTION; LANDSCAPE; TUMORS; NULL
AB In many applications, researchers are interested in making q pairwise comparisons among k test groups on the basis of m outcome variables. Often, m is very large. For example, such situations arise in gene expression microarray studies involving several experimental groups. Researchers are often not only interested in identifying differentially expressed genes between a given pair of experimental groups, but are also interested in making directional inferences such as whether a gene is up-or downregulated in one treatment group relative to another. In such situations, in addition to the usual errors such as false positive (Type I error) and false negative (Type II error), one may commit directional error (Type III error). For example, in a dose response microarray study, a gene may be declared to be upregulated in the high dose group compared to the low dose group when it is not. In this paper, we introduce a mixed directional false discovery rate (mdFDR) controlling procedure using weighted p-values to select positives in different directions. The weights are defined as the inverse of two times the proportion of either positive or negative discoveries. The proposed procedure has been proved mathematically to control the mdFDR at level a and to have a larger power (which is defined as the expected proportion of nontrue null hypotheses) than the GSP10 procedure proposed by Guo et al. (2010). Simulation studies and real data analysis are also conducted to show the outperformance of the proposed procedure than the GSP10 procedure.
C1 [Zhao, Haibing] Shanghai Univ Finance & Econ, Sch Stat & Management, Shanghai 200433, Peoples R China.
[Peddada, Shyamal D.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Cui, Xinping] Univ Calif Riverside, Dept Stat, Ctr Plant Cell Biol, Riverside, CA 92521 USA.
RP Cui, XP (reprint author), Univ Calif Riverside, Dept Stat, Ctr Plant Cell Biol, Riverside, CA 92521 USA.
EM xinping.cui@ucr.edu
FU National Natural Science Foundation of China (NSFC) [11101255];
University of California AES-CE RSAP grant [A01869]; NIH, National
Institute of Environmental Health Sciences [Z01 ES101744-04]
FX The research of H.Z. was supported by a grant from the National Natural
Science Foundation of China (NSFC) [No. 11101255]. The research of XC
was supported, in part, by University of California AES-CE RSAP grant
[A01869]. The research of SDP was supported, in part, by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences [Z01 ES101744-04].
NR 30
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U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0323-3847
EI 1521-4036
J9 BIOMETRICAL J
JI Biom. J.
PD JAN
PY 2015
VL 57
IS 1
SI SI
BP 144
EP 158
DI 10.1002/bimj.201300242
PG 15
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA AY4GO
UT WOS:000347536500011
PM 25410394
ER
PT J
AU Stratton, P
AF Stratton, P.
TI Gynecologic care after hematopoietic cell transplantation: a call to
action to include gynecologists in the transplant team
SO BONE MARROW TRANSPLANTATION
LA English
DT Editorial Material
ID PROGRESS
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
EM ps79c@nih.gov
NR 8
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JAN
PY 2015
VL 50
IS 1
BP 1
EP 2
DI 10.1038/bmt.2014.247
PG 2
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA AY8MD
UT WOS:000347806800001
PM 25365065
ER
PT J
AU Shah, NN
Wayne, AS
Grady, C
Fry, T
Wendler, D
AF Shah, N. N.
Wayne, A. S.
Grady, C.
Fry, T.
Wendler, D.
TI Children as hematopoietic cell donors in research: when is it
approvable?
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
ID G-CSF; MARROW; DONATION; BLOOD; TRANSPLANTATION; STATEMENT; RISK
AB With increasing frequency, allogeneic hematopoietic cell transplantation involving children is being performed in the research setting. Allogeneic hematopoietic cell transplantation, however, cannot be performed without a hematopoietic stem cell (HSC) donor. This donor is often a sibling of the recipient and may also be a child. In such circumstances, it is unclear whether or how the federal regulations for pediatric research apply to the minor donors. This introductory paper reviews the issues to be considered while evaluating studies that use HSCs obtained from minor donors and identifies areas where further research is needed. In the era of increasing applicability for donor-derived cellular therapies, we provide a suggested framework for determining when minor donors qualify as human research subjects and when their participation can be approved under the federal regulations.
C1 [Shah, N. N.; Wayne, A. S.; Fry, T.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wayne, A. S.] Univ So Calif, Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA USA.
[Grady, C.; Wendler, D.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Shah, NN (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1W-3750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Nirali.Shah@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Warren Grant
Magnuson Clinical Center
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Center for
Cancer Research and the Warren Grant Magnuson Clinical Center.
NR 13
TC 2
Z9 2
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JAN
PY 2015
VL 50
IS 1
BP 15
EP 19
DI 10.1038/bmt.2014.224
PG 5
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA AY8MD
UT WOS:000347806800004
PM 25330224
ER
PT J
AU Engels, EA
Landgren, O
Costello, R
Burton, D
Mailankody, S
Storek, J
AF Engels, E. A.
Landgren, O.
Costello, R.
Burton, D.
Mailankody, S.
Storek, J.
TI Serum immunoglobulin free light chains and post-transplant
lymphoproliferative disorder among allogeneic hematopoietic stem cell
transplant recipients
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
C1 [Engels, E. A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Landgren, O.] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA.
[Costello, R.; Burton, D.; Mailankody, S.] NCI, Multiple Myeloma Sect, Bethesda, MD 20892 USA.
[Storek, J.] Univ Calgary, Calgary, AB, Canada.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM engelse@exchange.nih.gov
FU Intramural NIH HHS
NR 10
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JAN
PY 2015
VL 50
IS 1
BP 146
EP 147
DI 10.1038/bmt.2014.213
PG 2
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA AY8MD
UT WOS:000347806800028
PM 25265459
ER
PT J
AU Sprung, CN
Ivashkevich, A
Forrester, HB
Redon, CE
Georgakilas, A
Martin, OA
AF Sprung, Carl N.
Ivashkevich, Alesia
Forrester, Helen B.
Redon, Christophe E.
Georgakilas, Alexandros
Martin, Olga A.
TI Oxidative DNA damage caused by inflammation may link to stress-induced
non-targeted effects
SO CANCER LETTERS
LA English
DT Review
DE Bystander effect; Non-targeted effects; Abscopal effects; Radiation
induced bystander effects; DNA damage; Ionizing radiation
ID RAT LUNG IRRADIATION; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INDUCED
ADAPTIVE RESPONSE; PRIMARY HUMAN FIBROBLASTS; DOUBLE-STRAND BREAKS;
MEDIATED INTERCELLULAR COMMUNICATION; HUMAN TISSUE MODELS; LOW-DOSE
RADIATION; EFFECTS IN-VIVO; FACTOR-KAPPA-B
AB A spectrum of radiation-induced non-targeted effects has been reported during the last two decades since Nagasawa and Little first described a phenomenon in cultured cells that was later called the "bystander effect". These non-targeted effects include radiotherapy-related abscopal effects, where changes in organs or tissues occur distant from the irradiated region. The spectrum of non-targeted effects continue to broaden over time and now embrace many types of exogenous and endogenous stressors that induce a systemic genotoxic response including a widely studied tumor microenvironment. Here we discuss processes and factors leading to DNA damage induction in non-targeted cells and tissues and highlight similarities in the regulation of systemic effects caused by different stressors. Crown Copyright (C) 2013 Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Sprung, Carl N.; Ivashkevich, Alesia; Forrester, Helen B.] Monash Univ, Ctr Innate Immun & Infect Dis, Monash Inst Med Res, Clayton, Vic 3168, Australia.
[Redon, Christophe E.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Georgakilas, Alexandros] Natl Tech Univ Athens, Dept Phys, Sch Appl Math & Phys Sci, GR-15773 Athens, Greece.
[Martin, Olga A.] Peter MacCallum Canc Ctr, Dept Radiat Oncol, Melbourne, Vic, Australia.
[Martin, Olga A.] Peter MacCallum Canc Ctr, Mol Radiat Biol Lab, Melbourne, Vic, Australia.
[Martin, Olga A.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia.
RP Sprung, CN (reprint author), Monash Univ, Ctr Innate Immunol & Infect Dis, Monash Inst Med Res, 27-31 Wright St, Clayton, Vic 3168, Australia.
EM carl.sprung@monash.edu
FU National Institute of Health [5U19AI067773-07]; round of the
priority-driven Collaborative Cancer Research Scheme [1002743];
Australian Government Department of Health and Ageing; Cancer Australia;
Australian National Health and Medical Research Council [10275598];
Australian National Breast Cancer Foundation [PG-08-06]; Victorian
Government's Operational Infrastructure Support Program; EU
[MC-CIG-303514]; COST ACTION [CM1202]
FX We thank Pavel Lobachevsky and Roger Martin for critical reading of the
manuscript. This project was supported through the National Institute of
Health (Grant 5U19AI067773-07) and the 2010 round of the priority-driven
Collaborative Cancer Research Scheme (Grant 1002743) and funded by the
Australian Government Department of Health and Ageing with the
assistance of Cancer Australia. Also, this work was supported by the
Australian National Health and Medical Research Council (Grant 10275598)
and the Australian National Breast Cancer Foundation (Grant PG-08-06;
http://www.nbcf.org.au/). Support was also provided by the Victorian
Government's Operational Infrastructure Support Program and A.
Georgakilas's funding is from EU grant MC-CIG-303514 and COST ACTION
CM1202 'Biomimetic Radical Chemistry'. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 175
TC 14
Z9 14
U1 0
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD JAN 1
PY 2015
VL 356
IS 1
SI SI
BP 72
EP 81
DI 10.1016/j.canlet.2013.09.008
PG 10
WC Oncology
SC Oncology
GA AY4ZP
UT WOS:000347583700010
PM 24041866
ER
PT J
AU Dabydeen, SA
Kang, K
Diaz-Cruz, ES
Alamri, A
Axelrod, ML
Bouker, KB
Al-Kharboosh, R
Clarke, R
Hennighausen, L
Furth, PA
AF Dabydeen, Sarah A.
Kang, Keunsoo
Diaz-Cruz, Edgar S.
Alamri, Ahmad
Axelrod, Margaret L.
Bouker, Kerrie B.
Al-Kharboosh, Rawan
Clarke, Robert
Hennighausen, Lothar
Furth, Priscilla A.
TI Comparison of tamoxifen and letrozole response in mammary preneoplasia
of ER and aromatase overexpressing mice defines an immune-associated
gene signature linked to tamoxifen resistance
SO CARCINOGENESIS
LA English
DT Article
ID BREAST-CANCER CELLS; ESTROGEN-RECEPTOR-ALPHA; EPITHELIAL-CELLS;
PATHWAYS; PREVENTION; NETWORKS; THERAPY; PROTEIN; HYPERPLASIA;
METASTASIS
AB Differential responses to tamoxifen and letrozole shown with two different lesions in the estrogen-ER pathway in genetically engineered mice, RNA-seq demonstrated an association of immune-related gene expression with tamoxifen resistance, and letrozole was an effective alternative when tamoxifen resistance was present.Response to breast cancer chemoprevention can depend upon host genetic makeup and initiating events leading up to preneoplasia. Increased expression of aromatase and estrogen receptor (ER) is found in conjunction with breast cancer. To investigate response or resistance to endocrine therapy, mice with targeted overexpression of Esr1 or CYP19A1 to mammary epithelial cells were employed, representing two direct pathophysiological interventions in estrogen pathway signaling. Both Esr1 and CYP19A1 overexpressing mice responded to letrozole with reduced hyperplastic alveolar nodule prevalence and decreased mammary epithelial cell proliferation. CYP19A1 overexpressing mice were tamoxifen sensitive but Esr1 overexpressing mice were tamoxifen resistant. Increased ER expression occurred with tamoxifen resistance but no consistent changes in progesterone receptor, pSTAT3, pSTAT5, cyclin D1 or cyclin E levels in association with response or resistance were found. RNA-sequencing (RNA-seq) was employed to seek a transcriptome predictive of tamoxifen resistance using these models and a second tamoxifen-resistant model, BRCA1 deficient/Trp53 haploinsufficient mice. Sixty-eight genes associated with immune system processing were upregulated in tamoxifen-resistant Esr1- and Brca1-deficient mice, whereas genes related to aromatic compound metabolic process were upregulated in tamoxifen-sensitive CYP19A1 mice. Interferon regulatory factor 7 was identified as a key transcription factor regulating these 68 immune processing genes. Two loci encoding novel transcripts with high homology to human immunoglobulin lambda-like polypeptide 1 were uniquely upregulated in the tamoxifen-resistant models. Letrozole proved to be a successful alternative to tamoxifen. Further study of transcriptional changes associated with tamoxifen resistance including immune-related genes could expand our mechanistic understanding and lead to biomarkers predictive of escape or response to endocrine therapies.
C1 [Dabydeen, Sarah A.; Diaz-Cruz, Edgar S.; Alamri, Ahmad; Axelrod, Margaret L.; Bouker, Kerrie B.; Al-Kharboosh, Rawan; Clarke, Robert; Furth, Priscilla A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Kang, Keunsoo] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Kang, Keunsoo] Dankook Univ, Dept Microbiol, Cheonan 330714, South Korea.
[Diaz-Cruz, Edgar S.] Belmont Univ, Coll Pharm, Dept Pharmaceut Social & Adm Sci, Nashville, TN 37212 USA.
[Alamri, Ahmad] King Khalid Univ, Coll Appl Med Sci, Clin Sci Lab, Abha 62529, Saudi Arabia.
[Furth, Priscilla A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Med, Washington, DC 20057 USA.
RP Furth, PA (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd NW,Res Bldg,Room 520A, Washington, DC 20057 USA.
EM paf3@georgetown.edu
RI Clarke, Robert/A-6485-2008
OI Clarke, Robert/0000-0002-9278-0854
FU National Institutes of Health (NIH) National Cancer Institute (NCI) [RO1
CA112176]; NIH NCI 'Research Supplements to Promote Diversity in
Health-Related Research' [CA112176]; Susan G. Komen for the Cure
Postdoctoral Fellowship grant [KG080359]; NIH T32 Ruth L. Kirschstein
National Research Service Award Institutional Training grant
[5T32CA009686-15]; Department of Defense Breast Cancer Postdoctoral
Fellowship Award [BC130883]; NIH, NCI [U54CA149147]; Saudi Arabian
Cultural Mission-King Abdullah Scholarship; NIH [IG20RR025828]; NIH NCI
[5P30CA051008]; Intramural Research Program (IRP) of National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK)
FX National Institutes of Health (NIH) National Cancer Institute (NCI) (RO1
CA112176 to P.A.F.); NIH NCI 'Research Supplements to Promote Diversity
in Health-Related Research' (CA112176 to support E.S.D.-C.); Susan G.
Komen for the Cure Postdoctoral Fellowship grant (KG080359 to support
E.S.D.-C.); NIH T32 Ruth L. Kirschstein National Research Service Award
Institutional Training grant (5T32CA009686-15 to support S.A.D. and
E.S.D.-C.); Department of Defense Breast Cancer Postdoctoral Fellowship
Award BC130883 (to K.B.B.); NIH, NCI U54CA149147 (to R.C.); Saudi
Arabian Cultural Mission-King Abdullah Scholarship (R.A.-K.); NIH
IG20RR025828 (Rodent Barrier Facility Equipment); NIH NCI 5P30CA051008
(Histology and Tissue, Tissue Culture and Animal Shared Resources). The
Intramural Research Program (IRP) of National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) funded part of this research.
NR 50
TC 4
Z9 4
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD JAN
PY 2015
VL 36
IS 1
BP 122
EP 132
DI 10.1093/carcin/bgu237
PG 11
WC Oncology
SC Oncology
GA AY9BM
UT WOS:000347844700017
PM 25421723
ER
PT J
AU Lan, Q
Smith, MT
Tang, XJ
Guo, WH
Vermeulen, R
Ji, ZY
Hu, W
Hubbard, AE
Shen, M
McHale, CM
Qiu, CY
Liu, SW
Reiss, B
Beane-Freeman, L
Blair, A
Ge, YC
Xiong, J
Li, LY
Rappaport, SM
Huang, HL
Rothman, N
Zhang, LP
AF Lan, Qing
Smith, Martyn T.
Tang, Xiaojiang
Guo, Weihong
Vermeulen, Roel
Ji, Zhiying
Hu, Wei
Hubbard, Alan E.
Shen, Min
McHale, Cliona M.
Qiu, Chuangyi
Liu, Songwang
Reiss, Boris
Beane-Freeman, Laura
Blair, Aaron
Ge, Yichen
Xiong, Jun
Li, Laiyu
Rappaport, Stephen M.
Huang, Hanlin
Rothman, Nathaniel
Zhang, Luoping
TI Chromosome-wide aneuploidy study of cultured circulating myeloid
progenitor cells from workers occupationally exposed to formaldehyde
SO CARCINOGENESIS
LA English
DT Article
ID IN-SITU HYBRIDIZATION; LONG ARM DELETION; INHALED FORMALDEHYDE;
POTENTIAL MECHANISMS; HEMATOPOIETIC STEM; OXIDATIVE STRESS;
RISK-ASSESSMENT; LEUKEMIA; BENZENE; LYMPHOCYTES
AB Formaldehyde (FA) is an economically important industrial chemical to which millions of people worldwide are exposed environmentally and occupationally. Recently, the International Agency for Cancer Research concluded that there is sufficient evidence that FA causes leukemia, particularly myeloid leukemia. To evaluate the biological plausibility of this association, we employed a chromosome-wide aneuploidy study approach, which allows the evaluation of aneuploidy and structural chromosome aberrations (SCAs) of all 24 chromosomes simultaneously, to analyze cultured myeloid progenitor cells from 29 workers exposed to relatively high levels of FA and 23 unexposed controls. We found statistically significant increases in the frequencies of monosomy, trisomy, tetrasomy and SCAs of multiple chromosomes in exposed workers compared with controls, with particularly notable effects for monosomy 1 [P = 6.02E-06, incidence rate ratio (IRR) = 2.31], monosomy 5 (P = 9.01E-06; IRR = 2.24), monosomy 7 (P = 1.57E-05; IRR = 2.17), trisomy 5 (P = 1.98E-05; IRR = 3.40) and SCAs of chromosome 5 (P = 0.024; IRR = 4.15). The detection of increased levels of monosomy 7 and SCAs of chromosome 5 is particularly relevant as they are frequently observed in acute myeloid leukemia. Our findings provide further evidence that leukemia-related cytogenetic changes can occur in the circulating myeloid progenitor cells of healthy workers exposed to FA, which may be a potential mechanism underlying FA-induced leukemogenesis.
C1 [Lan, Qing; Hu, Wei; Shen, Min; Beane-Freeman, Laura; Blair, Aaron; Rothman, Nathaniel] NIH, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Smith, Martyn T.; Guo, Weihong; Ji, Zhiying; Hubbard, Alan E.; McHale, Cliona M.; Rappaport, Stephen M.; Zhang, Luoping] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Tang, Xiaojiang; Qiu, Chuangyi; Ge, Yichen; Li, Laiyu; Huang, Hanlin] Guangdong Poisoning Control Ctr, Sci & Educ Dept, Guangzhou 510300, Guangdong, Peoples R China.
[Vermeulen, Roel; Reiss, Boris] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, NL-3508 Utrecht, Netherlands.
[Liu, Songwang] Qiaotou Hosp, Dept Occupat Hlth, Dongguan 523323, Guangdong, Peoples R China.
[Xiong, Jun] Dongguan Ctr Dis Control & Prevent, Dept Occupat Hlth, Guangzhou 523129, Guangdong, Peoples R China.
RP Zhang, LP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
EM qingl@mail.nih.gov; luoping@berkeley.edu
RI Beane Freeman, Laura/C-4468-2015; Vermeulen, Roel/F-8037-2011
OI Beane Freeman, Laura/0000-0003-1294-4124; Vermeulen,
Roel/0000-0003-4082-8163
FU National Cancer Institute; National Institute of Environmental Health
Sciences [R01ES017452, P42ES004705]
FX Intramural funds from the National Cancer Institute and National
Institute of Environmental Health Sciences (R01ES017452 to L.Z. and
P42ES004705 to M.T.S.).
NR 54
TC 8
Z9 9
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD JAN
PY 2015
VL 36
IS 1
BP 160
EP 167
DI 10.1093/carcin/bgu229
PG 8
WC Oncology
SC Oncology
GA AY9BM
UT WOS:000347844700021
PM 25391402
ER
PT J
AU Galluzzi, L
Bravo-San Pedro, JM
Vitale, I
Aaronson, SA
Abrams, JM
Adam, D
Alnemri, ES
Altucci, L
Andrews, D
Annicchiarico-Petruzzelli, M
Baehrecke, EH
Bazan, NG
Bertrand, MJ
Bianchi, K
Blagosklonny, MV
Blomgren, K
Borner, C
Bredesen, DE
Brenner, C
Campanella, M
Candi, E
Cecconi, F
Chan, FK
Chandel, NS
Cheng, EH
Chipuk, JE
Cidlowski, JA
Ciechanover, A
Dawson, TM
Dawson, VL
De Laurenzi, V
De Maria, R
Debatin, KM
Di Daniele, N
Dixit, VM
Dynlacht, BD
El-Deiry, WS
Fimia, GM
Flavell, RA
Fulda, S
Garrido, C
Gougeon, ML
Green, DR
Gronemeyer, H
Hajnoczky, G
Hardwick, JM
Hengartner, MO
Ichijo, H
Joseph, B
Jost, PJ
Kaufmann, T
Kepp, O
Klionsky, DJ
Knight, RA
Kumar, S
Lemasters, JJ
Levine, B
Linkermann, A
Lipton, SA
Lockshin, RA
Lopez-Otin, C
Lugli, E
Madeo, F
Malorni, W
Marine, JC
Martin, SJ
Martinou, JC
Medema, JP
Meier, P
Melino, S
Mizushima, N
Moll, U
Munoz-Pinedo, C
Nunez, G
Oberst, A
Panaretakis, T
Penninger, JM
Peter, ME
Piacentini, M
Pinton, P
Prehn, JH
Puthalakath, H
Rabinovich, GA
Ravichandran, KS
Rizzuto, R
Rodrigues, CM
Rubinsztein, DC
Rudel, T
Shi, Y
Simon, HU
Stockwell, BR
Szabadkai, G
Tait, SW
Tang, HL
Tavernarakis, N
Tsujimoto, Y
Vanden Berghe, T
Vandenabeele, P
Villunger, A
Wagner, EF
Walczak, H
White, E
Wood, WG
Yuan, J
Zakeri, Z
Zhivotovsky, B
Melino, G
Kroemer, G
AF Galluzzi, L.
Bravo-San Pedro, J. M.
Vitale, I.
Aaronson, S. A.
Abrams, J. M.
Adam, D.
Alnemri, E. S.
Altucci, L.
Andrews, D.
Annicchiarico-Petruzzelli, M.
Baehrecke, E. H.
Bazan, N. G.
Bertrand, M. J.
Bianchi, K.
Blagosklonny, M. V.
Blomgren, K.
Borner, C.
Bredesen, D. E.
Brenner, C.
Campanella, M.
Candi, E.
Cecconi, F.
Chan, F. K.
Chandel, N. S.
Cheng, E. H.
Chipuk, J. E.
Cidlowski, J. A.
Ciechanover, A.
Dawson, T. M.
Dawson, V. L.
De laurenzi, V.
De Maria, R.
Debatin, K-M
Di Daniele, N.
Dixit, V. M.
Dynlacht, B. D.
El-Deiry, W. S.
Fimia, G. M.
Flavell, R. A.
Fulda, S.
Garrido, C.
Gougeon, M-L
Green, D. R.
Gronemeyer, H.
Hajnoczky, G.
Hardwick, J. M.
Hengartner, M. O.
Ichijo, H.
Joseph, B.
Jost, P. J.
Kaufmann, T.
Kepp, O.
Klionsky, D. J.
Knight, R. A.
Kumar, S.
Lemasters, J. J.
Levine, B.
Linkermann, A.
Lipton, S. A.
Lockshin, R. A.
Lopez-Otin, C.
Lugli, E.
Madeo, F.
Malorni, W.
Marine, J-C
Martin, S. J.
Martinou, J-C
Medema, J. P.
Meier, P.
Melino, S.
Mizushima, N.
Moll, U.
Munoz-Pinedo, C.
Nunez, G.
Oberst, A.
Panaretakis, T.
Penninger, J. M.
Peter, M. E.
Piacentini, M.
Pinton, P.
Prehn, J. H.
Puthalakath, H.
Rabinovich, G. A.
Ravichandran, K. S.
Rizzuto, R.
Rodrigues, C. M.
Rubinsztein, D. C.
Rudel, T.
Shi, Y.
Simon, H-U
Stockwell, B. R.
Szabadkai, G.
Tait, S. W.
Tang, H. L.
Tavernarakis, N.
Tsujimoto, Y.
Vanden Berghe, Tom
Vandenabeele, P.
Villunger, A.
Wagner, E. F.
Walczak, H.
White, E.
Wood, W. G.
Yuan, J.
Zakeri, Z.
Zhivotovsky, B.
Melino, G.
Kroemer, G.
TI Essential versus accessory aspects of cell death: recommendations of the
NCCD 2015
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Review
ID MITOCHONDRIAL PERMEABILITY TRANSITION; TUMOR-NECROSIS-FACTOR;
APOPTOSIS-INDUCING FACTOR; MIXED LINEAGE KINASE; CYTOCHROME-C RELEASE;
ISCHEMIA-REPERFUSION INJURY; DOMAIN-LIKE PROTEIN; Q-VD-OPH;
OUTER-MEMBRANE PERMEABILIZATION; CASPASE INHIBITION SWITCHES
AB Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
C1 [Galluzzi, L.; Bravo-San Pedro, J. M.] Gustave Roussy Canc Ctr, Villejuif, France.
[Galluzzi, L.; Bravo-San Pedro, J. M.; Kepp, O.; Kroemer, G.] Ctr Rech Cordeliers, Equipe Labellisee Ligue Natl Contre Canc 11, F-75006 Paris, France.
[Galluzzi, L.; Kroemer, G.] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Bravo-San Pedro, J. M.; Kepp, O.; Kroemer, G.] Gustave Roussy, INSERM, U1138, Paris, France.
[Vitale, I.; De Maria, R.] Regina Elena Inst Canc Res, Rome, Italy.
[Aaronson, S. A.; Chipuk, J. E.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Oncol Sci, New York, NY 10029 USA.
[Abrams, J. M.] UT Southwestrn Med Ctr, Dept Cell Biol, Dallas, TX USA.
[Adam, D.] Univ Kiel, Inst Immunol, Kiel, Germany.
[Alnemri, E. S.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
[Altucci, L.] Seconda Univ Napoli, Dipartimento Biochim Biofis & Patol Gen, Naples, Italy.
[Andrews, D.] Univ Toronto, Dept Biochem & Med Biophys, Toronto, ON, Canada.
[Annicchiarico-Petruzzelli, M.] IRCCS, IDI, Biochem Lab, Rome, Italy.
[Baehrecke, E. H.] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA USA.
[Bazan, N. G.] Sch Med, Neurosci Ctr Excellence, New Orleans, LA USA.
[Bertrand, M. J.; Vanden Berghe, Tom; Vandenabeele, P.] VIB, Inflammat Res Ctr, Ghent, Belgium.
[Bertrand, M. J.; Vanden Berghe, Tom; Vandenabeele, P.] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium.
[Bianchi, K.] Canc Res UK Ctr Excellence, Barts Canc Inst, London, England.
[Bianchi, K.] Queen Mary Univ London, John Vane Sci Ctr, London, England.
[Blagosklonny, M. V.] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA.
[Blomgren, K.] Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.
[Borner, C.] Univ Freiburg, Inst Mol Med, D-79106 Freiburg, Germany.
[Borner, C.] Univ Freiburg, Spemann Grad Sch Biol & Med, D-79106 Freiburg, Germany.
[Bredesen, D. E.] Buck Inst Res Aging, Novato, CA USA.
[Bredesen, D. E.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Brenner, C.] INSERM, UMRS769, Chatenay Malabry, France.
[Brenner, C.] LabEx LERMIT, Chatenay Malabry, France.
[Brenner, C.] Univ Paris 11, Orsay, France.
[Campanella, M.] UCL, Dept Comparat Biomed Sci, London, England.
[Campanella, M.] UCL, Consortium Mitochondrial Res, London, England.
[Candi, E.; Melino, G.] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
[Cecconi, F.] IRCCS Fdn Santa Lucia, Lab Mol Neuroembryol, Rome, Italy.
[Cecconi, F.; Piacentini, M.] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy.
[Cecconi, F.] Danish Canc Soc Res Ctr, Unit Cell Stress & Survival, Copenhagen, Denmark.
[Chan, F. K.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA.
[Chandel, N. S.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[Cheng, E. H.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Cheng, E. H.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Cidlowski, J. A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA.
[Ciechanover, A.] Technion Israel Inst Technol, Rappaport Fac Med & Res Inst, Tumor & Vasc Biol Res Ctr, Haifa, Israel.
[Dawson, T. M.; Dawson, V. L.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Solomon H Snyder Dept Neurosci,Dept Neurol Pharma, Baltimore, MD USA.
[Dawson, T. M.; Dawson, V. L.] Adrienne Helis Malvin Med Res Fdn, New Orleans, LA USA.
[De laurenzi, V.] Gabriele Annunzio Univ, Dept Expt & Clin Sci, Chieti, Italy.
[Debatin, K-M] Ulm Univ Med Ctr, Dept Pediat & Adolescent Med, Ulm, Germany.
[Di Daniele, N.] Univ Roma Tor Vergata, Dept Syst Med, Rome, Italy.
[Dixit, V. M.] Genentech Inc, Dept Physiol Chem, South San Francisco, CA USA.
[Dynlacht, B. D.] NYU, Sch Med, Smilow Res Ctr, Dept Pathol, New York, NY USA.
[Dynlacht, B. D.] NYU, Sch Med, Smilow Res Ctr, Inst Canc, New York, NY USA.
[El-Deiry, W. S.] Penn State Coll Med, Penn State Hershey Canc Inst, Dept Med Hematol Oncol, Lab Translat Oncol & Expt Canc Therapeut, Hershey, PA USA.
[Fimia, G. M.] Univ Salento, Dept Biol & Environm Sci & Technol DiSTeBA, Lecce, Italy.
[Fimia, G. M.] IRCCS, Natl Inst Infect Dis Lazzaro Spallanzani, Dept Epidemiol & Preclin Res, Rome, Italy.
[Flavell, R. A.] Yale Sch Med, Dept Immunobiol, New Haven, CT USA.
[Fulda, S.] Goethe Univ Frankfurt, Inst Expt Canc Res Pediat, Frankfurt, Germany.
[Garrido, C.] INSERM, U866, Dijon, France.
[Garrido, C.] Univ Burgundy, Fac Med, Dijon, France.
[Gougeon, M-L] Inst Pasteur, Infect & Epidemiol Dept, Antiviral Immun Biotherapy & Vaccine Unit, Paris, France.
[Green, D. R.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
[Gronemeyer, H.] IGBMC, Dept Funct Genom & Canc, Illkirch Graffenstaden, France.
[Hajnoczky, G.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
[Hardwick, J. M.; Tang, H. L.] Johns Hopkins Univ, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Hengartner, M. O.] Univ Zurich, Inst Mol Life Sci, Zurich, Switzerland.
[Ichijo, H.] Univ Tokyo, Grad Sch Pharmaceut Sci, Lab Cell Signaling, Tokyo, Japan.
[Joseph, B.; Panaretakis, T.] Canc Centrum Karolinska CCK, Dept Oncol Pathol, Stockholm, Sweden.
[Jost, P. J.] Tech Univ Munich, Dept Med Hematol, D-80290 Munich, Germany.
[Kaufmann, T.] Univ Bern, Fac Med, Inst Pharmacol, Bern, Switzerland.
[Knight, R. A.] UCL, Inst Child Hlth, Med Mol Biol Unit, London, England.
[Knight, R. A.; Melino, G.] Med Res Council Toxicol Unit, Leicester, Leics, England.
[Kumar, S.] Univ S Australia, Ctr Canc Biol, Adelaide, SA 5001, Australia.
[Kumar, S.] Univ Adelaide, Sch Med, Adelaide, SA, Australia.
[Kumar, S.] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia.
[Lemasters, J. J.] Med Univ S Carolina, Dept Drug Discovery & Biomed Sci & Biochem & Mol, Charleston, SC 29425 USA.
[Levine, B.] Univ Texas SW Med Ctr Dallas, Ctr Autophagy Res, Dallas, TX 75390 USA.
[Linkermann, A.] Univ Kiel, Div Nephrol & Hypertens, Kiel, Germany.
[Lipton, S. A.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Lipton, S. A.] Sanford Burnham Ctr Neurosci Aging & Stem Cel Res, La Jolla, CA USA.
[Lipton, S. A.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
[Lipton, S. A.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Lockshin, R. A.] St Johns Univ, Dept Biol Sci, Queens, NY USA.
[Lopez-Otin, C.] Univ Oviedo, Inst Univ Oncol IUOPA, Fac Med, Dept Biochem & Mol Biol, Oviedo, Spain.
[Lugli, E.] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Milan, Italy.
[Madeo, F.] Graz Univ, Inst Mol Biosci, Graz, Austria.
[Malorni, W.] Ist Superiore Sanita, Dept Therapeut Res & Med Evaluat, Rome, Italy.
[Malorni, W.] San Raffaele Inst, Sulmona, Italy.
[Marine, J-C] Ctr Biol Dis, Lab Mol Canc Biol, Leuven, Belgium.
[Marine, J-C] Ctr Human Genet, Lab Mol Canc Biol, Leuven, Belgium.
[Martin, S. J.] Trinity Coll Dublin, Smurfit Inst, Dept Genet, Dublin, Ireland.
[Martinou, J-C] Univ Geneva, Dept Cell Biol, Geneva, Switzerland.
[Medema, J. P.] Univ Amsterdam, Acad Med Ctr, Lab Experiments Oncol & Radiobiol LEXOR, NL-1105 AZ Amsterdam, Netherlands.
[Meier, P.] Breakthrough Toby Robins Breast Canc Res Ctr, Inst Canc Res, London, England.
[Melino, S.] Univ Roma Tor Vergata, Dept Chem Sci & Technol, Rome, Italy.
[Mizushima, N.; Munoz-Pinedo, C.] Univ Tokyo, Fac Med, Cell Death Regulat Grp, Tokyo 113, Japan.
[Moll, U.] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
[Munoz-Pinedo, C.] Bellvitge Biomed Res Inst IDIBELL, Cell Death Regulat Grp, Barcelona, Spain.
[Nunez, G.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA.
[Nunez, G.] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI USA.
[Oberst, A.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA.
[Penninger, J. M.] Austrian Acad Sci, Inst Mol Biotechnol, A-1010 Vienna, Austria.
[Peter, M. E.] Northwestern Univ, Feinberg Sch Med, Dept Hematol Oncol, Chicago, IL 60611 USA.
[Pinton, P.] Univ Ferrara, Dept Morphol Surg & Expt Med, Sect Pathol Oncol & Expt Biol, I-44100 Ferrara, Italy.
[Pinton, P.] Univ Ferrara, LTTA Ctr, I-44100 Ferrara, Italy.
[Prehn, J. H.] Royal Coll Surg, Dept Physiol & Med Phys, Dublin, Ireland.
[Puthalakath, H.] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem, Melbourne, Vic, Australia.
[Rabinovich, G. A.] Consejo Nacl Invest Cient & Tecn, Inst Biol Med Expt IBYME, Immunopathol Lab, RA-1033 Buenos Aires, DF, Argentina.
[Ravichandran, K. S.] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA.
[Rizzuto, R.; Szabadkai, G.] Univ Padua, Dept Biomed Sci, Padua, Italy.
[Rodrigues, C. M.] Univ Lisbon, Fac Pharm, Res Inst Med, P-1699 Lisbon, Portugal.
[Rubinsztein, D. C.] Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England.
[Rudel, T.] Univ Wurzburg, Dept Microbiol, D-97070 Wurzburg, Germany.
[Shi, Y.] Soochow Univ, Soochow Inst Translat Med, Suzhou, Peoples R China.
[Simon, H-U] Univ Bern, Inst Pharmacol, Bern, Switzerland.
[Stockwell, B. R.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Stockwell, B. R.] Columbia Univ, Dept Chem, New York, NY 10027 USA.
[Szabadkai, G.] UCL, Dept Cell & Dev Biol, London, England.
[Szabadkai, G.] UCL, Consortium Mitochondrial Res, London, England.
[Tait, S. W.] Canc Res UK Beatson Inst, Glasgow, Lanark, Scotland.
[Tait, S. W.] Univ Glasgow, Inst Canc Sci, Glasgow, Lanark, Scotland.
[Tavernarakis, N.] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Crete, Greece.
[Tavernarakis, N.] Univ Crete, Fac Med, Dept Basic Sci, Iraklion, Crete, Greece.
[Tsujimoto, Y.] Osaka Med Ctr Canc & Cardiovasc Dis, Osaka, Japan.
[Vandenabeele, P.] Univ Ghent, Methusalem Program, B-9000 Ghent, Belgium.
[Villunger, A.] Med Univ Innsbruck, Bioctr, Div Dev Immunol, A-6020 Innsbruck, Austria.
[Wagner, E. F.] Spanish Natl Canc Res Ctr CNIO, Canc Cell Biol Program, Madrid, Spain.
[Walczak, H.] UCL, Inst Canc, Ctr Cell Death Canc & Inflammat CCCI, London, England.
[White, E.] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA.
[Wood, W. G.] Univ Minnesota, Sch Med, Dept Pharmacol, Minneapolis, MN 55455 USA.
[Wood, W. G.] VA Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA.
[Yuan, J.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Zakeri, Z.] Queens Coll, Dept Biol, Queens, NY USA.
[Zakeri, Z.] CUNY, Grad Ctr, Queens, NY USA.
[Zhivotovsky, B.] Karolinska Inst, Inst Environm Med, Div Toxicol, S-10401 Stockholm, Sweden.
[Zhivotovsky, B.] Moscow MV Lomonosov State Univ, Fac Fundamental Med, Moscow, Russia.
[Kroemer, G.] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France.
RP Galluzzi, L (reprint author), Ctr Rech Cordeliers, Equipe Apoptose Canc & Immun 11, 15 Rue Ecole Med, F-75006 Paris, France.
EM deadoc@vodafone.it; kroemer@orange.fr
RI Piacentini, Mauro/I-2411-2016; Lopez-Otin, Carlos/C-6657-2013;
Tavernarakis, Nektarios/B-9684-2013; Pinton, Paolo/J-8025-2012;
Bertrand, Mathieu/P-6465-2016; Prehn, Jochen/A-3928-2010; Jost,
Philipp/S-4962-2016; iMed.ULisboa, iMed.ULisboa/C-6292-2014;
iMed.ULisboa, CellFun /A-4244-2014; Gronemeyer, Hinrich/H-7002-2016;
Marine, Jean-Christophe/K-3292-2016; Chan, Francis/E-9647-2014;
Vandenabeele, Peter/C-8597-2009; Debatin, Klaus-Michael/J-9704-2014;
Bravo San Pedro, Jose Manuel/F-1680-2015; Penninger, Josef/I-6860-2013;
Wagner, Erwin/G-9637-2012; Marine, Jean Christophe/J-2237-2015;
Gronemeyer, Hinrich/G-6240-2011; Rodrigues, Cecilia/M-3572-2013;
Munoz-Pinedo, Cristina/B-6118-2008; Malorni, Walter/G-5874-2016; Adam,
Dieter/E-9763-2010;
OI Piacentini, Mauro/0000-0003-2919-1296; Lopez-Otin,
Carlos/0000-0001-6964-1904; Tavernarakis, Nektarios/0000-0002-5253-1466;
Pinton, Paolo/0000-0001-7108-6508; Prehn, Jochen/0000-0003-3479-7794;
Jost, Philipp/0000-0003-2454-0362; Gronemeyer,
Hinrich/0000-0001-9454-2449; Panaretakis,
Theocharis/0000-0001-5754-6950; Kaufmann, Thomas/0000-0001-9906-874X;
VITALE, ILIO/0000-0002-5918-1841; malorni, walter/0000-0002-1223-7000;
Zhivotovsky, Boris/0000-0002-2238-3482; Flavell,
Richard/0000-0003-4461-0778; Dawson, Valina/0000-0002-2915-3970; Marine,
Jean-Christophe/0000-0003-2433-9837; Chan, Francis/0000-0002-4803-8353;
Debatin, Klaus-Michael/0000-0002-8397-1886; Penninger,
Josef/0000-0002-8194-3777; Wagner, Erwin/0000-0001-7872-0196;
Gronemeyer, Hinrich/0000-0001-9454-2449; Rodrigues,
Cecilia/0000-0002-4829-754X; Munoz-Pinedo, Cristina/0000-0002-9120-664X;
Adam, Dieter/0000-0002-5668-5032; Linkermann,
Andreas/0000-0001-6287-9725; Cecconi, Francesco/0000-0002-5614-4359;
Andrews, David/0000-0002-9266-7157; Bravo-San Pedro, Jose
Manuel/0000-0002-5781-1133; MELINO, SONIA MICHAELA/0000-0001-7694-5279;
Blomgren, Klas/0000-0002-0476-7271; Kumar, Sharad/0000-0001-7126-9814;
Chipuk, Jerry Edward/0000-0002-1337-842X
FU European Research Council [233294]; Medical Research Council
[MC_U132670600]; NCI NIH HHS [R01 CA097061, R01 CA130893, R01 CA163591,
R01 CA169291, R01 CA170702]; NIAAA NIH HHS [R01 AA021191]; NIAID NIH HHS
[R01 AI044828]; NICHD NIH HHS [P01 HD029587, R01 HD066319]; NIDA NIH HHS
[P50 DA000266]; NIDDK NIH HHS [R01 DK073336, R56 DK037034]; NIGMS NIH
HHS [R01 GM053396, R01 GM072124, R01 GM096208]; NINDS NIH HHS [P50
NS038377, R01 NS086890]; Wellcome Trust [095317, 100140]
NR 336
TC 181
Z9 184
U1 12
U2 92
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD JAN
PY 2015
VL 22
IS 1
SI SI
BP 58
EP 73
DI 10.1038/cdd.2014.137
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AY9AJ
UT WOS:000347841600008
PM 25236395
ER
PT J
AU Ursano, RJ
Heeringa, SG
Stein, MB
Jain, S
Raman, R
Sun, XY
Chiu, WT
Colpe, LJ
Fullerton, CS
Gilman, SE
Hwang, I
Naifeh, JA
Nock, MK
Rosellini, AJ
Sampson, NA
Schoenbaum, M
Zaslavsky, AM
Kessler, RC
AF Ursano, Robert J.
Heeringa, Steven G.
Stein, Murray B.
Jain, Sonia
Raman, Rema
Sun, Xiaoying
Chiu, Wai Tat
Colpe, Lisa J.
Fullerton, Carol S.
Gilman, Stephen E.
Hwang, Irving
Naifeh, James A.
Nock, Matthew K.
Rosellini, Anthony J.
Sampson, Nancy A.
Schoenbaum, Michael
Zaslavsky, Alan M.
Kessler, Ronald C.
TI PREVALENCE AND CORRELATES OF SUICIDAL BEHAVIOR AMONG NEW SOLDIERS IN THE
US ARMY: RESULTS FROM THE ARMY STUDY TO ASSESS RISK AND RESILIENCE IN
SERVICEMEMBERS (ARMY STARRS)
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE military personnel; prevalence; suicide; suicide ideation; suicide
attempt
ID RANDOMIZED CONTROLLED-TRIAL; NATIONAL-COMORBIDITY-SURVEY; PSYCHOLOGICAL
DISORDERS; ADOLESCENTS; MILITARY; THERAPY; DESIGN; RATES
AB BackgroundThe prevalence of suicide among U.S. Army soldiers has risen dramatically in recent years. Prior studies suggest that most soldiers with suicidal behaviors (i.e., ideation, plans, and attempts) had first onsets prior to enlistment. However, those data are based on retrospective self-reports of soldiers later in their Army careers. Unbiased examination of this issue requires investigation of suicidality among new soldiers.
MethodThe New Soldier Study (NSS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) used fully structured self-administered measures to estimate preenlistment histories of suicide ideation, plans, and attempts among new soldiers reporting for Basic Combat Training in 2011-2012. Survival models examined sociodemographic correlates of each suicidal outcome.
ResultsLifetime prevalence estimates of preenlistment suicide ideation, plans, and attempts were 14.1, 2.3, and 1.9%, respectively. Most reported onsets of suicide plans and attempts (73.3-81.5%) occurred within the first year after onset of ideation. Odds of these lifetime suicidal behaviors among new soldiers were positively, but weakly associated with being female, unmarried, religion other than Protestant or Catholic, and a race/ethnicity other than non-Hispanic White, non-Hispanic Black, or Hispanic.
ConclusionsLifetime prevalence estimates of suicidal behaviors among new soldiers are consistent with retrospective reports of preenlistment prevalence obtained from soldiers later in their Army careers. Given that prior suicidal behaviors are among the strongest predictors of later suicides, consideration should be given to developing methods of obtaining valid reports of preenlistment suicidality from new soldiers to facilitate targeting of preventive interventions. (C) 2014 Wiley Periodicals, Inc.
C1 [Ursano, Robert J.; Fullerton, Carol S.; Naifeh, James A.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[Heeringa, Steven G.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, Murray B.; Jain, Sonia; Raman, Rema; Sun, Xiaoying] 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.
[Raman, Rema] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
[Chiu, Wai Tat; Hwang, Irving; Rosellini, Anthony J.; Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
[Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MD USA.
[Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MD USA.
[Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA USA.
RP Ursano, RJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM robert.ursano@usuhs.edu
RI Gilman, Stephen/E-7632-2010
OI Gilman, Stephen/0000-0002-8331-6419
FU Department of the Army; U.S. Department of Health and Human Services;
NIH/NIMH [U01MH087981]
FX Contract grant sponsor: Department of the Army, U.S. Department of
Health and Human Services, and NIH/NIMH; Contract grant number:
U01MH087981.
NR 29
TC 10
Z9 10
U1 5
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JAN
PY 2015
VL 32
IS 1
BP 3
EP 12
DI 10.1002/da.22317
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AY9MI
UT WOS:000347874800002
PM 25338964
ER
PT J
AU Rosellini, AJ
Heeringa, SG
Stein, MB
Ursano, RJ
Chiu, WT
Colpe, LJ
Fullerton, CS
Gilman, SE
Hwang, I
Naifeh, JA
Nock, MK
Petukhova, M
Sampson, NA
Schoenbaum, M
Zaslavsky, AM
Kessler, RC
AF Rosellini, Anthony J.
Heeringa, Steven G.
Stein, Murray B.
Ursano, Robert J.
Chiu, Wai Tat
Colpe, Lisa J.
Fullerton, Carol S.
Gilman, Stephen E.
Hwang, Irving
Naifeh, James A.
Nock, Matthew K.
Petukhova, Maria
Sampson, Nancy A.
Schoenbaum, Michael
Zaslavsky, Alan M.
Kessler, Ronald C.
TI LIFETIME PREVALENCE OF DSM-IV MENTAL DISORDERS AMONG NEW SOLDIERS IN THE
US ARMY: RESULTS FROM THE ARMY STUDY TO ASSESS RISK AND RESILIENCE IN
SERVICEMEMBERS (ARMY STARRS)
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE military personnel; mental disorders; prevalence; epidemiology;
demographics
ID COMORBIDITY SURVEY REPLICATION; AGE-OF-ONSET;
POSTTRAUMATIC-STRESS-DISORDER; HEALTH-CARE; PSYCHIATRIC-DISORDERS;
MILITARY PERSONNEL; COMBAT EXPOSURE; SUBSTANCE USE; EVENTS; CIDI
AB BackgroundThe prevalence of 30-day mental disorders with retrospectively reported early onsets is significantly higher in the U.S. Army than among socio-demographically matched civilians. This difference could reflect high prevalence of preenlistment disorders and/or high persistence of these disorders in the context of the stresses associated with military service. These alternatives can to some extent be distinguished by estimating lifetime disorder prevalence among new Army recruits.
MethodsThe New Soldier Study (NSS) in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) used fully structured measures to estimate lifetime prevalence of 10 DSM-IV disorders in new soldiers reporting for Basic Combat Training in 2011-2012 (n = 38,507). Prevalence was compared to estimates from a matched civilian sample. Multivariate regression models examined socio-demographic correlates of disorder prevalence and persistence among new soldiers.
ResultsLifetime prevalence of having at least one internalizing, externalizing, or either type of disorder did not differ significantly between new soldiers and civilians, although three specific disorders (generalized anxiety, posttraumatic stress, and conduct disorders) and multimorbidity were significantly more common among new soldiers than civilians. Although several socio-demographic characteristics were significantly associated with disorder prevalence and persistence, these associations were uniformly weak.
ConclusionsNew soldiers differ somewhat, but not consistently, from civilians in lifetime preenlistment mental disorders. This suggests that prior findings of higher prevalence of current disorders with preenlistment onsets among soldiers than civilians are likely due primarily to a more persistent course of early-onset disorders in the context of the special stresses experienced by Army personnel. (C) 2014 Wiley Periodicals, Inc.
C1 [Rosellini, Anthony J.; Chiu, Wai Tat; Hwang, Irving; Petukhova, Maria; Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, 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, 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.
[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.
[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.
[Nock, Matthew K.] Harvard Univ, Dept Psychol, Cambridge, MA USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM Kessler@hcp.med.harvard.edu
RI Gilman, Stephen/E-7632-2010
OI Gilman, Stephen/0000-0002-8331-6419
FU Department of the Army; U.S. Department of Health and Human Services;
NIH/NIMH [U01MH087981]
FX Contract grant sponsor: Department of the Army, U.S. Department of
Health and Human Services, and NIH/NIMH; contract grant number:
U01MH087981.
NR 52
TC 11
Z9 11
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JAN
PY 2015
VL 32
IS 1
BP 13
EP 24
DI 10.1002/da.22316
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AY9MI
UT WOS:000347874800003
PM 25338841
ER
PT J
AU Van, C
Williams, JS
Kunkel, TA
Peterson, CL
AF Van, Christopher
Williams, Jessica S.
Kunkel, Thomas A.
Peterson, Craig L.
TI Deposition of histone H2A.Z by the SWR-C remodeling enzyme prevents
genome instability
SO DNA REPAIR
LA English
DT Article
DE Chromatin remodeling; Genome instability; Mismatch repair; Exonuclease
1; H2A.Z
ID DNA-POLYMERASE-EPSILON; MISMATCH REPAIR; CHROMATIN; REPLICATION;
MUTATIONS; DYNAMICS; ERRORS; ALPHA; DELTA
AB The yeast SWR-C chromatin remodeling enzyme catalyzes chromatin incorporation of the histone variant H2A.Z which plays roles in transcription, DNA repair, and chromosome segregation. Dynamic incorporation of H2A.Z by SWR-C also enhances the ability of exonuclease I (Exo1) to process DNA ends during repair of double strand breaks. Given that Exo1 also participates in DNA replication and mismatch repair, here we test whether SWR-C influences DNA replication fidelity. We find that inactivation of SWR-C elevates the spontaneous mutation rate of a strain encoding a L612M variant of DNA polymerase (Pol) delta, with a single base mutation signature characteristic of lagging strand replication errors. However, this genomic instability does not solely result from reduced Exo1 function, because single base mutator effects are seen in both Exo1-proficient and Exo1-deficient po13-L612M swr1 Delta strains. The data are consistent with the possibility that incorporation of the H2A.Z variant by SWR-C may stimulate Exo1 activity, as well as enhance the fidelity of replication by Pol delta, the repair of mismatches generated by Pol delta, or both. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Van, Christopher; Peterson, Craig L.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
[Williams, Jessica S.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Williams, Jessica S.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Craig.Peterson@umassmed.edu
FU Division of Intramural Research of the NIH, NIEHS [Z01 ES065070]; NIH
[GM054096]; American Cancer Society - Lakeshore Division Postdoctoral
Fellowship
FX We thank Alan Clark and Scott Lujan for helpful comments on the
manuscript and Kunkel lab members for data previously generated in the
lab. We are grateful to Grace Kissling for statistical expertise and the
NIEHS Molecular Genetics Core Facility for sequencing of 5-FOA-resistant
mutants. This work was supported by Project Z01 ES065070 to T.A.K. from
the Division of Intramural Research of the NIH, NIEHS, and by a grant
from the NIH (GM054096) to C.L.P. C.V. was supported by an American
Cancer Society - Lakeshore Division Postdoctoral Fellowship.
NR 26
TC 3
Z9 3
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD JAN
PY 2015
VL 25
BP 9
EP 14
DI 10.1016/j.dnarep.2014.10.010
PG 6
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA AY9KA
UT WOS:000347867600002
PM 25463393
ER
PT J
AU Siebrasse, EA
Pastrana, DV
Nguyen, NL
Wang, A
Roth, MJ
Holland, SM
Freeman, AF
McDyer, J
Buck, CB
Wang, D
AF Siebrasse, Erica A.
Pastrana, Diana V.
Nguyen, Nang L.
Wang, Annie
Roth, Mark J.
Holland, Steven M.
Freeman, Alexandra F.
McDyer, John
Buck, Christopher B.
Wang, David
TI WU Polyomavirus in Respiratory Epithelial Cells from Lung Transplant
Patient with Job Syndrome
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID KI; INFECTION; UPDATE
AB We detected WU polyomavirus (WUPyV) in a bronchoalveolar lavage sample from lungs transplanted into a recipient with Job syndrome by using immunoassays specific for the WUPyV viral protein 1. Co-staining for an epithelial cell marker identified most WUPyV viral protein 1 positive cells as respiratory epithelial cells.
C1 [Siebrasse, Erica A.; Nguyen, Nang L.; Wang, Annie; Wang, David] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Pastrana, Diana V.; Roth, Mark J.; Holland, Steven M.; Freeman, Alexandra F.; Buck, Christopher B.] NIH, Bethesda, MD 20892 USA.
[McDyer, John] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
RP Wang, D (reprint author), Washington Univ, Dept Mol Microbiol, Sch Med, Campus Box 8230,660 S Euclid Ave, St Louis, MO 63110 USA.
EM davewang@borcim.wustl.edu
OI Buck, Christopher/0000-0003-3165-8094
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
NIH [P30AR048335]; Division of Intramural Research, National Institute
of Allergy and Infectious Diseases, NIH [R21AI095922]; Children's
Discovery Institute at Washington University in St. Louis; NIH
Intramural Research Program; Center for Cancer Research; Department of
Defense through the National Defense Science and Engineering Graduate
Fellowship Program; National Institute of Allergy and Infectious
Diseases
FX Experimental support was provided by the Hybridoma Facility of the
Rheumatic Diseases Core Center. This study was supported by the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH (award
no. P30AR048335); the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, NIH; grant R21AI095922 to
D.W.; the Children's Discovery Institute at Washington University in St.
Louis; and the NIH Intramural Research Program, with support from the
Center for Cancer Research and National Institute of Allergy and
Infectious Diseases. E.A.S. was supported by the Department of Defense
through the National Defense Science and Engineering Graduate Fellowship
Program.
NR 12
TC 7
Z9 7
U1 0
U2 0
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JAN
PY 2015
VL 21
IS 1
BP 103
EP 106
DI 10.3201/eid2101.140855
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AY3SW
UT WOS:000347503700017
PM 25531075
ER
PT J
AU Kenyon, N
Wang, L
Spornick, N
Khaibullina, A
Almeida, LEF
Cheng, Y
Wang, JC
Guptill, V
Finkel, JC
Quezado, ZMN
AF Kenyon, Nicholas
Wang, Li
Spornick, Nicholas
Khaibullina, Alfia
Almeida, Luis E. F.
Cheng, Yao
Wang, Jichuan
Guptill, Virginia
Finkel, Julia C.
Quezado, Zenaide M. N.
TI Sickle cell disease in mice is associated with sensitization of sensory
nerve fibers
SO EXPERIMENTAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Sickle cell; pain; nociception; sine wave; somatosensory; fetal
hemoglobin
ID CURRENT VOCALIZATION THRESHOLD; WAVE ELECTRICAL-STIMULATION; NOCICEPTION
ASSAY; NEUROPATHIC PAIN; MOUSE MODELS; RAT MODEL; ANEMIA; COLD;
HEMOGLOBIN; ACTIVATION
AB The pain phenotype in sickle cell disease (SCD) patients is highly variable. A small percentage of SCD patients experience many vaso-occlusive crises/year, 5% of patients account for over 30% of pain episodes, while 39% report few episodes of severe pain. Clearly, a better understanding of the pathobiology of SCD is needed to improve its therapy. Humanized sickle cell mice recapitulate several phenotypes of SCD patients and provide a model for the study of SCD pain. Researchers have shown that one strain of humanized SCD mice, the BERK strain, has abnormal pain phenotype. However, the nociception phenotype of another humanized SCD mouse strain, the Townes strain, has not been described. In a large cross-sectional study of BERK and Townes SCD mice, we examined thermosensory response and sensory nerve fiber function using sine-wave electrical stimulation at 2000, 250, and 5Hz to stimulate preferentially A, A, and C sensory nerve fibers, respectively. We found that BERK and Townes mice, compared to respective controls, had decreases in 2000, 250, and 5Hz current vocalization thresholds in patterns that suggest sensitization of a broad spectrum of sensory nerve fibers. In addition, the pattern of sensitization of sensory fibers varied according to strain, sex, age, and mouse genotype. In a similarly variable pattern, Townes and BERKs also had significantly altered sensitivity to noxious thermal stimuli in agreement with what has been shown by others. In summary, the analysis of somatosensory function using sine-wave electrical stimulation in humanized sickle cell mice suggests that in SCD, both myelinated and unmyelinated, fibers are sensitized. The pattern of sensory fiber sensitization is distinct from that observed in pain models of neuropathic and inflammatory pain. These findings raise the possibility that sensitization of a broad spectrum of sensory fibers might contribute to the altered and variable nociception phenotype in SCD.
C1 [Kenyon, Nicholas; Wang, Li; Spornick, Nicholas; Khaibullina, Alfia; Almeida, Luis E. F.; Finkel, Julia C.; Quezado, Zenaide M. N.] George Washington Univ, Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Childrens Res Inst,Div Pain Med,Sch Med & Hlth Sc, Washington, DC 20010 USA.
[Cheng, Yao; Wang, Jichuan] Childrens Natl Med Ctr, Ctr Translat Sci, Div Biostat & Study Methodol, Washington, DC 20010 USA.
[Guptill, Virginia] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Quezado, ZMN (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Childrens Res Inst,Div Pain Med,Sch Med & Hlth Sc, Washington, DC 20010 USA.
EM zquezado@childrensnational.org
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
FU National Institutes of Health Clinical Center, NIH; Sheikh Zayed
Institute for Pediatric Surgical Innovation
FX The authors are grateful to LaShon Middleton and Sayuri Kamimura for
expert technical support during experiments, to Aral C. Greene and Nina
Afsar for editorial help, and to Edward C.C. Wong, MD and Nannette
Poidven for measurements of fetal hemoglobin concentration. This work
was supported by the Intramural Program from the National Institutes of
Health Clinical Center, NIH and the Sheikh Zayed Institute for Pediatric
Surgical Innovation.
NR 48
TC 5
Z9 5
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1535-3702
EI 1535-3699
J9 EXP BIOL MED
JI Exp. Biol. Med.
PD JAN
PY 2015
VL 240
IS 1
BP 87
EP 98
DI 10.1177/1535370214544275
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AZ1CH
UT WOS:000347977400010
PM 25070860
ER
PT J
AU Lessard, JC
Kalinin, A
Bible, PW
Morasso, MI
AF Lessard, Juliane C.
Kalinin, Alexandr
Bible, Paul W.
Morasso, Maria I.
TI Calmodulin 4 is dispensable for epidermal barrier formation and wound
healing in mice
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE calcium-binding protein; epidermis; skin barrier; wound repair
ID DIFFERENTIATION; PROTEIN; SCARF; EXPRESSION
AB Calcium-mediated signals play important roles in epidermal barrier formation, skin homoeostasis and wound repair. Calmodulin 4 (Calm4) is a small, Ca2+-binding protein with strong expression in suprabasal keratinocytes. In mice, Calm4 first appears in the skin at the time of barrier formation, and its expression increases in response to epidermal barrier challenges. In this study, we report the generation of Calm4 knockout mice and provide evidence that Calm4 is dispensable for epidermal barrier formation, maintenance and repair.
C1 [Lessard, Juliane C.; Kalinin, Alexandr; Bible, Paul W.; Morasso, Maria I.] NIAMSD, Skin Biol Lab, Bethesda, MD 20892 USA.
RP Morasso, MI (reprint author), NIAMSD, Skin Biol Lab, Bldg 50,Room 1523, Bethesda, MD 20892 USA.
EM morasso@nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the NIH [ZIA AR041124-15]
FX The authors thank Dr. Gustavo Gutierrez-Cruz and Dr. Hong-Wei Sun for
help with the RNAseq experiments, Kimberly Hilsen for assistance with
mouse breeding and Dr. Mary Ann Stepp for input relating to the wound
healing studies. This research was supported by the Intramural Research
Program of the National Institute of Arthritis and Musculoskeletal and
Skin Diseases of the NIH (ZIA AR041124-15 to M.I. Morasso).
NR 9
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0906-6705
EI 1600-0625
J9 EXP DERMATOL
JI Exp. Dermatol.
PD JAN
PY 2015
VL 24
IS 1
BP 55
EP 57
DI 10.1111/exd.12568
PG 3
WC Dermatology
SC Dermatology
GA AY6WP
UT WOS:000347703900012
PM 25316000
ER
PT J
AU Stephenson, D
Perry, D
Bens, C
Bain, LJ
Berry, D
Krams, M
Sperling, R
Dilts, D
Luthman, J
Hanna, D
McKew, J
Temple, R
Fields, FO
Salloway, S
Katz, R
AF Stephenson, Diane
Perry, Dan
Bens, Cynthia
Bain, Lisa J.
Berry, Donald
Krams, Michael
Sperling, Reisa
Dilts, David
Luthman, Johan
Hanna, Debra
McKew, John
Temple, Robert
Fields, F. Owen
Salloway, Stephen
Katz, Russell
TI Charting a path toward combination therapy for Alzheimer's disease
SO EXPERT REVIEW OF NEUROTHERAPEUTICS
LA English
DT Review
DE Alzheimer's disease; combination therapy; collaboration; novel therapy;
co-development
ID DRUG DEVELOPMENT; BREAST-CANCER; CLINICAL-TRIALS; MAJOR DISEASES;
BIOMARKERS; CHEMOTHERAPY; MEMANTINE; RECOMMENDATIONS; PERSPECTIVES;
COALITION
AB It is acknowledged that progress in combined therapeutic approaches for Alzheimer's disease (AD) will require an unprecedented level of collaboration. At a meeting co-hosted by the Accelerate Cure/Treatments for Alzheimer's Disease Coalition and the Critical Path Institute, investigators from industry, academia and regulatory agencies agreed on the need for combinatorial approaches to treating AD. The need for advancing multiple targets includes recognition for novel adaptive trial designs that incorporate existing and new biomarkers to evaluate drug effects independently and in combination. A combination trial now being planned may test drugs targeting different pathogenic pathways or multiple targets along a common pathway. Collaborations and consortia-based strategies are pivotal for success and a regulatory framework is recommended for success.
C1 [Stephenson, Diane] Crit Path Inst, CAMD, Tucson, AZ 85718 USA.
[Perry, Dan; Bens, Cynthia] Alliance Aging Res, Accelerate Cure Treatments Alzheimers Dis ACT AD, Washington, DC USA.
[Berry, Donald] Berry Consultants LLC, Austin, TX 78746 USA.
[Krams, Michael] Janssen Pharmaceut, Neurol Franchise, Titusville, NJ USA.
[Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA.
[Dilts, David] OHSU Knight Canc Inst, Div Management, Ctr Management Res Healthcare, Portland, OR USA.
[Luthman, Johan] Eisai Pharmaceut, Visakhapatnam, Andhra Pradesh, India.
[Hanna, Debra] Crit Path TB Drug Regimens Regulatory Sci Consort, Tucson, AZ USA.
[McKew, John] NIH, Therapeut Dev Branch, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Temple, Robert] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA.
[Fields, F. Owen] Pfizer, Worldwide Res & Dev, Regulatory Strategy, New York, NY USA.
[Salloway, Stephen] Butler Hosp, Memory & Aging Program, Providence, RI 02906 USA.
RP Stephenson, D (reprint author), Crit Path Inst, CAMD, Tucson, AZ 85718 USA.
EM DStephenson@c-path.org
RI Akbar, Afrah/C-2001-2016
FU Eli Lily; Eisai; Avid; Janssen; Biogen Idec; Merck Lilly; Roche
Genentech
FX M Krams is an employee of Janssen R&D. R Sperling is a consultant to
Roche, Isis, Genentech, Janssen and has received research support from
Eli Lily, Eisai, Avid and Janssen. J Luthman is an employee of Eisai Inc
and owns shares in AstraZeneca & Merck Inc. F Owen Fields is employed by
Pfizer and has stock options in Pfizer. S Salloway has received research
support from Biogen Idec, Merck Lilly, Roche & Genentech. 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 30
TC 10
Z9 10
U1 1
U2 6
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1473-7175
EI 1744-8360
J9 EXPERT REV NEUROTHER
JI Expert Rev. Neurother.
PD JAN
PY 2015
VL 15
IS 1
SI SI
BP 107
EP 113
DI 10.1586/14737175.2015.995168
PG 7
WC Clinical Neurology; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA AY8KQ
UT WOS:000347802800009
PM 25540951
ER
PT J
AU Bergamaschi, C
Kulkarni, V
Rosati, M
Alicea, C
Jalah, R
Chen, S
Bear, J
Sardesai, NY
Valentin, A
Felber, BK
Pavlakis, GN
AF Bergamaschi, C.
Kulkarni, V.
Rosati, M.
Alicea, C.
Jalah, R.
Chen, S.
Bear, J.
Sardesai, N. Y.
Valentin, A.
Felber, B. K.
Pavlakis, G. N.
TI Intramuscular delivery of heterodimeric IL-15 DNA in macaques produces
systemic levels of bioactive cytokine inducing proliferation of NK and T
cells
SO GENE THERAPY
LA English
DT Article
ID NATURAL-KILLER-CELLS; HUMORAL IMMUNE-RESPONSES; SIV-INFECTED MACAQUES;
PHASE-I TRIAL; NONHUMAN-PRIMATES; RHESUS MACAQUES; RECEPTOR-ALPHA;
SOLUBLE IL-15R-ALPHA; INTERLEUKIN (IL)-15; TRANS PRESENTATION
AB Interleukin-15 (IL-15) is a common.-chain cytokine that has a significant role in the activation and proliferation of T and NK cells and holds great potential in fighting infection and cancer. We have previously shown that bioactive IL-15 in vivo comprises a complex of the IL-15 chain with the soluble or cell-associated IL-15 receptor alpha (IL-15R alpha) chain, which together form the IL-15 heterodimer. We have generated DNA vectors expressing the heterodimeric IL-15 by optimizing mRNA expression and protein trafficking. Repeated administration of these DNA plasmids by intramuscular injection followed by in vivo electroporation in rhesus macaques resulted in sustained high levels of IL-15 in plasma, with no significant toxicity. Administration of DNAs expressing heterodimeric IL-15 also resulted in an increased frequency of NK and T cells undergoing proliferation in peripheral blood. Heterodimeric IL-15 led to preferential expansion of CD8(+)NK cells, all memory CD8(+) T-cell subsets and effector memory CD4(+) T cells. Expression of heterodimeric IL-15 by DNA delivery to the muscle is an efficient procedure to obtain high systemic levels of bioactive cytokine, without the toxicity linked to the high transient cytokine peak associated with protein injection.
C1 [Bergamaschi, C.; Kulkarni, V.; Alicea, C.; Jalah, R.; Bear, J.; Felber, B. K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Rosati, M.; Chen, S.; Valentin, A.; Pavlakis, G. N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Sardesai, N. Y.] Inovio Pharmaceut, Plymouth Meeting, PA USA.
RP Pavlakis, GN (reprint author), NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
EM george.pavlakis@nih.gov
FU National Cancer Institute, National Institutes of Health (NCI/NIH)
FX This work was funded in part by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (NCI/NIH). We
thank GR Pilkington for discussions and assistance and KA Goetz for
technical assistance; D Weiss, J Treece, A Cristillo, M Ferrari and
staff at Advanced Bioscience Laboratory for support; and T Jones for
editorial assistance.
NR 63
TC 4
Z9 5
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD JAN
PY 2015
VL 22
IS 1
BP 76
EP 86
DI 10.1038/gt.2014.84
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA AY8FN
UT WOS:000347790000009
PM 25273353
ER
PT J
AU Teixeira, AL
de Souza, RT
Zanetti, MV
Brunoni, AR
Busatto, GF
Zarate, CA
Gattaz, WF
Machado-Vieira, R
AF Teixeira, Antonio L.
de Souza, Rafael T.
Zanetti, Marcus V.
Brunoni, Andre R.
Busatto, Geraldo F.
Zarate, Carlos A., Jr.
Gattaz, Wagner F.
Machado-Vieira, Rodrigo
TI Increased plasma levels of soluble TNF receptors 1 and 2 in bipolar
depression and impact of lithium treatment
SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE bipolar disorder; bipolar depression; lithium; sTNFR1; sTNFR2
ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY MARKERS; RATING-SCALE; SERUM-LEVELS;
DISORDER; CYTOKINES; METAANALYSIS; SCHIZOPHRENIA; BIOMARKERS; ALPHA
AB ObjectiveTNF system (TNF and its soluble receptors sTNFR1 and 2) has been investigated as a potential molecular target in bipolar disorder. The aim of the study was to compare plasma levels of these receptors in unmedicated bipolar depressed patients compared with healthy controls, and to evaluate the effects of a 6-week lithium treatment on sTNFR1 and sTNFR2 levels.
MethodsThe study enrolled 29 patients with unmedicated bipolar disorder in a major depressive episode and 27 matched controls. Patients had blood collected at baseline and after 6weeks of lithium treatment. The concentration of sTNFRs was measured by ELISA.
ResultssTNFR1 and sTNFR2 levels were significantly increased in bipolar depression in comparison with healthy subjects. Lithium treatment did not significantly change sTNFR1 and sTNFR2 levels from baseline to endpoint. There was no correlation between improvement in depressive symptoms and the change in sTNFR1 or sTNFR1 levels.
ConclusionThese results reinforce the involvement of an activated immune response system in the pathophysiology of bipolar disorder, with no impact of lithium treatment on the related biomarkers. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Teixeira, Antonio L.] Univ Fed Minas Gerais, Sch Med, Interdisciplinary Lab Med Investigat, Belo Horizonte, MG, Brazil.
[de Souza, Rafael T.; Zanetti, Marcus V.; Brunoni, Andre R.; Gattaz, Wagner F.; Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, Neurosci Lab, LIM 27, Sao Paulo, Brazil.
[Zanetti, Marcus V.; Busatto, Geraldo F.] Univ Sao Paulo, Inst & Dept Psychiat, Lab Psychiat Neuroimaging, LIM 21, Sao Paulo, Brazil.
[Zarate, Carlos A., Jr.; Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
RP Teixeira, AL (reprint author), Univ Fed Minas Gerais, Fac Med, Lab Interdisciplinar Invest Med, Sala 281,Av Alfredo Balena,190 Santa Efigenia, BR-30130100 Belo Horizonte, MG, Brazil.
EM altexr@gmail.com
RI Brunoni, Andre/H-8394-2012; Busatto, Geraldo/D-4431-2009;
MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Brunoni, Andre/0000-0002-6310-3571; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
FU CNPq; Minas Gerais Research Foundation (Fapemig); Sao Paulo Research
Foundation (Fapesp, Brazil) [2009/14891-9]
FX This work was funded by CNPq, Minas Gerais Research Foundation
(Fapemig), and Sao Paulo Research Foundation (Fapesp, Brazil
2009/14891-9).
NR 31
TC 7
Z9 7
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-6222
EI 1099-1077
J9 HUM PSYCHOPHARM CLIN
JI Hum. Psychopharmacol.-Clin. Exp.
PD JAN
PY 2015
VL 30
IS 1
BP 52
EP 56
DI 10.1002/hup.2450
PG 5
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry;
Psychology
GA AY6XA
UT WOS:000347704900006
PM 25572309
ER
PT J
AU Traynor, BJ
Renton, AE
AF Traynor, Bryan J.
Renton, Alan E.
TI Exploring the Epigenetics of Alzheimer Disease
SO JAMA NEUROLOGY
LA English
DT Editorial Material
ID DNA METHYLATION; BRAIN; SORL1; LOCI
C1 [Traynor, Bryan J.; Renton, Alan E.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Traynor, Bryan J.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, 35 Convent Dr,Porter Neurosci Bldg,Room 1A-110, Bethesda, MD 20892 USA.
EM traynorb@mail.nih.gov
FU Intramural NIH HHS; NIA NIH HHS [Z01-AG000949-02]
NR 9
TC 3
Z9 3
U1 0
U2 6
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 JAN
PY 2015
VL 72
IS 1
BP 8
EP 9
DI 10.1001/jamaneurol.2014.3057
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA AY8PI
UT WOS:000347815300002
PM 25365705
ER
PT J
AU Christen, WG
Glynn, RJ
Gaziano, JM
Darke, AK
Crowley, JJ
Goodman, PJ
Lippman, SM
Lad, TE
Bearden, JD
Goodman, GE
Minasian, LM
Thompson, IM
Blanke, CD
AF Christen, William G.
Glynn, Robert J.
Gaziano, J. Michael
Darke, Amy K.
Crowley, John J.
Goodman, Phyllis J.
Lippman, Scott M.
Lad, Thomas E.
Bearden, James D.
Goodman, Gary E.
Minasian, Lori M.
Thompson, Ian M., Jr.
Blanke, Charles D.
TI Age-Related Cataract in Men in the Selenium and Vitamin E Cancer
Prevention Trial Eye Endpoints Study A Randomized Clinical Trial
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID GLUTATHIONE-PEROXIDASE ACTIVITY; SENILE CATARACT; ANTIOXIDANT VITAMINS;
PROSTATE-CANCER; PROTECTIVE ROLE; LENS OPACITIES; BETA-CAROTENE; FINNISH
MEN; SUPPLEMENTATION; SELECT
AB IMPORTANCE Observational studies suggest a role for dietary nutrients such as vitamin E and selenium in cataract prevention. However, the results of randomized clinical trials of vitamin E supplements and cataract have been disappointing and are not yet available for selenium.
OBJECTIVE To test whether long-term supplementation with selenium and vitamin E affects the incidence of cataract in a large cohort of men.
DESIGN, SETTING, AND PARTICIPANTS The Selenium and Vitamin E Cancer Prevention Trial (SELECT) Eye Endpoints Study was an ancillary study of the Southwest Oncology Group-coordinated SELECT, a randomized placebo-controlled 4-arm trial of selenium and vitamin E conducted among 35 533 men, 50 years and older for African American participants and 55 years and older for all other men, at 427 participating sites in the United States, Canada, and Puerto Rico. A total of 11 267 SELECT participants from 128 SELECT sites participated in the SELECT Eye Endpoints ancillary study.
INTERVENTIONS Individual supplements of selenium (200 mu g per day from L-selenomethionine) and vitamin E (400 IU per day of all rac-a-tocopheryl acetate). MAIN OUTCOMES AND MEASURES Incident cataract was defined as a lens opacity, age related in origin, and responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-reports confirmed by medical record review. Cataract extraction was defined as the surgical removal of an incident cataract.
RESULTS During a mean (SD) of 5.6 (1.2) years of treatment and follow-up, 389 cases of cataract were documented. There were 185 cataracts in the selenium group and 204 in the no selenium group (hazard ratio, 0.91; 95% CI, 0.75-1.11; P =.37). For vitamin E, there were 197 cases in the treated group and 192 in the placebo group (hazard ratio, 1.02; 95% CI, 0.84-1.25; P =.81). Similar results were observed for cataract extraction.
CONCLUSIONS AND RELEVANCE These data from a large cohort of apparently healthy men indicate that long-term daily supplementation with selenium and/or vitamin E is unlikely to have a large beneficial effect on age-related cataract.
C1 [Christen, William G.; Glynn, Robert J.; Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA.
[Gaziano, J. Michael] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA 02215 USA.
[Gaziano, J. Michael] VA Boston Healthcare Syst, Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Darke, Amy K.; Crowley, John J.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, Southwest Oncol Grp Stat Ctr, Seattle, WA 98104 USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, Off Director, San Diego, CA 92103 USA.
[Lad, Thomas E.] Jesse Brown VA Med Ctr, Chicago, IL USA.
[Bearden, James D.] Spartanburg Reg Med Ctr, Upstate Carolina Community Clin Oncol Program, Spartanburg, SC USA.
[Goodman, Gary E.] Swedish Med Ctr, Washington, DC USA.
[Minasian, Lori M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, Dept Urol, San Antonio, TX 78229 USA.
[Blanke, Charles D.] Oregon Hlth & Sci Univ, Knight Canc Inst, Southwest Oncol Grp Chairs Off, Portland, OR 97201 USA.
[Blanke, Charles D.] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Urol, Cleveland, OH 44106 USA.
RP Christen, WG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA.
EM wchristen@rics.bwh.harvard.edu
FU Public Health Service - National Cancer Institute, National Institutes
of Health, Department of Health and Human Services [CA37429]; National
Center for Complementary and Alternative Medicine; [EY014418]
FX This work was supported by grant EY014418 and in part by grant CA37429
from the Public Health Service Cooperative Agreement awarded by the
National Cancer Institute, National Institutes of Health, Department of
Health and Human Services, and the National Center for Complementary and
Alternative Medicine.
NR 43
TC 10
Z9 10
U1 0
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JAN
PY 2015
VL 133
IS 1
BP 17
EP 24
DI 10.1001/jamaophthalmol.2014.3478
PG 8
WC Ophthalmology
SC Ophthalmology
GA AZ1AJ
UT WOS:000347972500003
PM 25232809
ER
PT J
AU Kessler, RC
Warner, CH
Ivany, C
Petukhova, MV
Rose, S
Bromet, EJ
Brown, M
Cai, TX
Colpe, LJ
Cox, KL
Fullerton, CS
Gilman, SE
Gruber, MJ
Heeringa, SG
Lewandowski-Romps, L
Li, JL
Millikan-Bell, A
Naifeh, JA
Nock, MK
Rosellini, AJ
Sampson, NA
Schoenbaum, M
Stein, MB
Wessely, S
Zaslavsky, AM
Ursano, RJ
AF Kessler, Ronald C.
Warner, Christopher H.
Ivany, Christopher
Petukhova, Maria V.
Rose, Sherri
Bromet, Evelyn J.
Brown, Millard, III
Cai, Tianxi
Colpe, Lisa J.
Cox, Kenneth L.
Fullerton, Carol S.
Gilman, Stephen E.
Gruber, Michael J.
Heeringa, Steven G.
Lewandowski-Romps, Lisa
Li, Junlong
Millikan-Bell, Amym.
Naifeh, James A.
Nock, Matthew K.
Rosellini, Anthony J.
Sampson, Nancy A.
Schoenbaum, Michael
Stein, Murray B.
Wessely, Simon
Zaslavsky, Alan M.
Ursano, Robert J.
CA Army STARRS Collaborators
TI Predicting Suicides After Psychiatric Hospitalization in US Army
Soldiers The Army Study to Assess Risk and Resilience in Servicemembers
(Army STARRS)
SO JAMA PSYCHIATRY
LA English
DT Article
ID DECISION-SUPPORT-SYSTEMS; INPATIENT CARE; PREVENTION; DISCHARGE;
METAANALYSIS; REGRESSION; DEPRESSION; ATTEMPTORS; BEHAVIOR; PERIODS
AB IMPORTANCE The US Army experienced a sharp increase in soldier suicides beginning in 2004. Administrative data reveal that among those at highest risk are soldiers in the 12 months after inpatient treatment of a psychiatric disorder.
OBJECTIVE To develop an actuarial risk algorithm predicting suicide in the 12 months after US Army soldier inpatient treatment of a psychiatric disorder to target expanded posthospitalization care.
DESIGN, SETTING, AND PARTICIPANTS There were 53 769 hospitalizations of active duty soldiers from January 1, 2004, through December 31, 2009, with International Classification of Diseases, Ninth Revision, Clinical Modification psychiatric admission diagnoses. Administrative data available before hospital discharge abstracted from a wide range of data systems (sociodemographic, US Army career, criminal justice, and medical or pharmacy) were used to predict suicides in the subsequent 12 months using machine learning methods (regression trees and penalized regressions) designed to evaluate cross-validated linear, nonlinear, and interactive predictive associations.
MAIN OUTCOMES AND MEASURES Suicides of soldiers hospitalized with psychiatric disorders in the 12 months after hospital discharge.
RESULTS Sixty-eight soldiers died by suicide within 12 months of hospital discharge (12.0% of all US Army suicides), equivalent to 263.9 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total US Army. The strongest predictors included sociodemographics (male sex [odds ratio (OR), 7.9; 95% CI, 1.9-32.6] and late age of enlistment [OR, 1.9; 95% CI, 1.0-3.5]), criminal offenses (verbal violence [OR, 2.2; 95% CI, 1.2-4.0] and weapons possession [OR, 5.6; 95% CI, 1.7-18.3]), prior suicidality [OR, 2.9; 95% CI, 1.7-4.9], aspects of prior psychiatric inpatient and outpatient treatment (eg, number of antidepressant prescriptions filled in the past 12 months [OR, 1.3; 95% CI, 1.1-1.7]), and disorders diagnosed during the focal hospitalizations (eg, nonaffective psychosis [OR, 2.9; 95% CI, 1.2-7.0]). A total of 52.9% of posthospitalization suicides occurred after the 5% of hospitalizations with highest predicted suicide risk (3824.1 suicides per 100 000 person-years). These highest-risk hospitalizations also accounted for significantly elevated proportions of several other adverse posthospitalization outcomes (unintentional injury deaths, suicide attempts, and subsequent hospitalizations).
CONCLUSIONS AND RELEVANCE The high concentration of risk of suicide and other adverse outcomes might justify targeting expanded posthospitalization interventions to soldiers classified as having highest posthospitalization suicide risk, although final determination requires careful consideration of intervention costs, comparative effectiveness, and possible adverse effects.
C1 [Kessler, Ronald C.; Petukhova, Maria V.; Rose, Sherri; Gruber, Michael J.; Rosellini, Anthony J.; Sampson, Nancy A.; Zaslavsky, Alan M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Warner, Christopher H.] Blanchfield Army Community Hosp, Dept Behav Med, Ft Campbell, KY USA.
[Ivany, Christopher; Brown, Millard, III] US Army Off Surg Gen, Falls Church, VA USA.
[Bromet, Evelyn J.] SUNY Stony Brook, Sch Med, Dept Psychiat, Stony Brook, NY 11794 USA.
[Cai, Tianxi; Li, Junlong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
[Cox, Kenneth L.; Millikan-Bell, Amym.] US Army Publ Hlth Command, Aberdeen Proving Ground, MD USA.
[Fullerton, Carol S.; Naifeh, James A.; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 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.; Lewandowski-Romps, Lisa] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[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, Deapartment Family & Prevent Med, La Jolla, CA 92093 USA.
[Stein, Murray B.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Wessely, Simon] Kings Coll London, Kings Ctr Mil Hlth Res, London WC2R 2LS, England.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave,Ste 215, Boston, MA 02115 USA.
EM kessler@hcp.med.harvard.edu
RI Gilman, Stephen/E-7632-2010; Wessely, Simon/A-8713-2008
OI Gilman, Stephen/0000-0002-8331-6419;
FU US Department of the Army; National Institute of Mental Health, National
Institutes of Health, US Department of Health and Human Services;
[U01MH087981]
FX The Army STARRS was sponsored by the US Department of the Army and
funded under cooperative agreement U01MH087981 with the National
Institute of Mental Health, National Institutes of Health, US Department
of Health and Human Services.
NR 48
TC 28
Z9 28
U1 6
U2 23
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 JAN
PY 2015
VL 72
IS 1
BP 49
EP 57
DI 10.1001/jamapsychiatry.2014.1754
PG 9
WC Psychiatry
SC Psychiatry
GA AY5KJ
UT WOS:000347610700007
PM 25390793
ER
PT J
AU Zeitler, EP
Piccini, JP
Hellkamp, AS
Whellan, DJ
Jackson, KP
Ellis, SJ
Kraus, WE
Keteyian, SJ
Kitzman, DW
Ewald, GA
Fleg, JL
Pina, IL
O'Connor, CM
AF Zeitler, Emily P.
Piccini, Jonathan P.
Hellkamp, Anne S.
Whellan, David J.
Jackson, Kevin P.
Ellis, Stephen J.
Kraus, William E.
Keteyian, Steven J.
Kitzman, Dalane W.
Ewald, Gregory A.
Fleg, Jerome L.
Pina, Ileana L.
O'Connor, Christopher M.
CA HF-ACTION Investigators
TI Exercise Training and Pacing Status in Patients With Heart Failure:
Results From HF-ACTION
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Article
DE Heart failure; exercise; implanted cardiac pacemaker; mortality
ID RANDOMIZED CONTROLLED-TRIAL; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR;
CARDIAC RESYNCHRONIZATION THERAPY; INVESTIGATING OUTCOMES; PERFORMANCE;
BENEFIT; DISEASE; UPDATE
AB Background: We sought to determine if outcomes with exercise training in heart failure (HF) vary according to ventricular pacing type.
Methods and Results: Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) randomized 2,331 outpatients with HF and left ventricular ejection fraction <= 35% to usual care plus exercise training or usual care alone. We examined the relationship between outcomes and randomized treatment according to ventricular pacing status with the use of Cox proportional hazards modeling. In HF-ACTION 1,118 patients (48%) had an implanted cardiac rhythm device: 683 with right ventricular (RV) and 435 with biventricular (BiV) pacemakers. Patients with pacing devices were older, more frequently white, and had lower peak VO2 (P < .001 for all). Peak VO2 improved similarly with training in groups with and without pacing devices. The primary composite end point-all-cause death or hospitalization was reduced only in patients randomized to exercise training without a device (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.67-0.93 [P = .004]; RV lead: HR 1.04, 95% CI 0.84-1.28 [P = .74]; BiV pacing: HR 1.05, 95% CI 0.82-1.34 [P = .72]; interaction P = .058).
Conclusions: Exercise training may improve exercise capacity in patients with implanted cardiac devices. However, the apparent beneficial effects of exercise on hospitalization or death may be attenuated in patients with implanted cardiac devices and requires further study.
C1 [Zeitler, Emily P.; Piccini, Jonathan P.; Jackson, Kevin P.; Ellis, Stephen J.; Kraus, William E.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol,Dept Med, Durham, NC 27710 USA.
[Hellkamp, Anne S.] Duke Clin Res Inst, Durham, NC USA.
[Whellan, David J.] Thomas Jefferson Univ, Dept Med, Div Cardiol, Philadelphia, PA 19107 USA.
[Keteyian, Steven J.] Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA.
[Kitzman, Dalane W.] Wake Forest Univ, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27109 USA.
[Ewald, Gregory A.] Washington Univ, Div Cardiovasc Dis, St Louis, MO USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Pina, Ileana L.] Albert Einstein Coll Med, Dept Med, Div Cardiol, New York, NY USA.
RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol, POB 17969, Durham, NC 27710 USA.
EM jonathan.piccini@duke.edu
OI Hellkamp, Anne/0000-0003-0919-4502
FU National Institutes of Health [5U01HL063747, RU01HL066482, 5UO1HL06694];
Boston Scientific
FX HF-ACTION was funded by the National Institutes of Health (5U01HL063747
to C.M.O., RU01HL066482 to I.L.P., and 5UO1HL06694 to S.J.K.). The
present work was supported by a grant from Boston Scientific to J.P.P.,
D.J.W., and C.M.O. The content of this manuscript is solely the
responsibility of the authors and does not necessarily represent the
official views of the NHLBI, NIH, or the Department of Health and Human
Services.
NR 16
TC 0
Z9 0
U1 0
U2 1
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
EI 1532-8414
J9 J CARD FAIL
JI J. Card. Fail.
PD JAN
PY 2015
VL 21
IS 1
BP 60
EP 67
DI 10.1016/j.cardfail.2014.10.004
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AY9KR
UT WOS:000347869300009
PM 25463413
ER
PT J
AU Jiang, CT
Xie, C
Li, F
Zhang, LM
Nichols, RG
Krausz, KW
Cai, JW
Qi, YP
Fang, ZZ
Takahashi, S
Tanaka, N
Desai, D
Amin, SG
Albert, I
Patterson, AD
Gonzalez, FJ
AF Jiang, Changtao
Xie, Cen
Li, Fei
Zhang, Limin
Nichols, Robert G.
Krausz, Kristopher W.
Cai, Jingwei
Qi, Yunpeng
Fang, Zhong-Ze
Takahashi, Shogo
Tanaka, Naold
Desai, Dhimant
Amin, Shantu G.
Albert, Istvan
Patterson, Andrew D.
Gonzalez, Frank J.
TI Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty
liver disease
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID INDUCED INSULIN-RESISTANCE; BILE-ACID-HOMEOSTASIS; HUMAN GUT MICROBIOTA;
DIET-INDUCED OBESITY; CHOLESTEROL 7-ALPHA-HYDROXYLASE; HEPATIC
STEATOSIS; GENE-EXPRESSION; MICE; FXR; METABOLISM
AB Nonalcoholic fatty liver disease (NAFLD) is a major worldwide health problem. Recent studies suggest that the gut microbiota influences NAFLD pathogenesis. Here, a murine model of high-fat diet-induced (HFD-induced) NAFLD was used, and the effects of alterations in the gut microbiota on NAFLD were determined. Mice treated with antibiotics or tempol exhibited altered bile acid composition, with a notable increase in conjugated bile acid metabolites that inhibited intestinal farnesoid X receptor (FXR) signaling. Compared with control mice, animals with intestine-specific Fxr disruption had reduced hepatic triglyceride accumulation in response to a HFD. The decrease in hepatic triglyceride accumulation was mainly due to fewer circulating ceramides, which was in part the result of lower expression of ceramide synthesis genes. The reduction of ceramide levels in the ileum and serum in tempol- or antibiotic-treated mice fed a HFD resulted in downregulation of hepatic SREBP1C and decreased de novo lipogenesis. Administration of C16:0 ceramide to antibiotic-treated mice fed a HFD reversed hepatic steatosis. These studies demonstrate that inhibition of an intestinal FXR/ceramide axis mediates gut microbiota-associated NAFLD development, linking the microbiome, nuclear receptor signaling, and NAFLD. This work suggests that inhibition of intestinal FXR is a potential therapeutic target for NAFLD treatment.
C1 [Jiang, Changtao; Xie, Cen; Li, Fei; Krausz, Kristopher W.; Qi, Yunpeng; Fang, Zhong-Ze; Tanaka, Naold; Desai, Dhimant; Amin, Shantu G.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jiang, Changtao] Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Key Lab Mol Cardiovasc Sci,Minist Educ, Beijing 100871, Peoples R China.
[Zhang, Limin; Nichols, Robert G.; Cai, Jingwei; Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Zhang, Limin; Nichols, Robert G.; Cai, Jingwei; Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Zhang, Limin] Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance, CAS Key Lab Magnet Resonance Biol Syst, Wuhan, Peoples R China.
[Desai, Dhimant; Amin, Shantu G.] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA USA.
[Albert, Istvan] Penn State Univ, Bioinformat Consulting Ctr, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM adp117@psu.edu; gonzalef@mail.nih.gov
RI limin, zhang/O-8208-2016; Patterson, Andrew/G-3852-2012
OI limin, zhang/0000-0001-5689-948X; Patterson, Andrew/0000-0003-2073-0070
FU Intramural Research Program of the Center for Cancer Research, NCI, NIH;
National Institutes of Environmental Health Sciences [ES022186];
Pennsylvania Department of Health using Tobacco CURE Funds
FX We thank Xin Pan and Jie Liu for help with analysis of mitochondrial
isolation and functional studies, Toren Finkel for use of the Seahorse
XF 96 analyzer, and Linda G. Byrd and John Buckley for technical
assistance with the mouse studies. This work was supported by the
Intramural Research Program of the Center for Cancer Research, NCI, NIH
and by the National Institutes of Environmental Health Sciences
(ES022186, to A.D. Patterson). Sequencing was provided by the Penn State
Genomics Core Facility (University Park, Pennsylvania, USA). This
project is funded in part by a grant with the Pennsylvania Department of
Health using Tobacco CURE Funds. The Department specifically disclaims
responsibility for any analyses, interpretations, or conclusions of this
work.
NR 68
TC 72
Z9 73
U1 7
U2 45
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JAN
PY 2015
VL 125
IS 1
BP 386
EP 402
DI 10.1172/JCI76738
PG 17
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AY7NS
UT WOS:000347747300040
PM 25500885
ER
PT J
AU Grahnemo, L
Jochems, C
Andersson, A
Engdahl, C
Ohlsson, C
Islander, U
Carlsten, H
AF Grahnemo, Louise
Jochems, Caroline
Andersson, Annica
Engdahl, Cecilia
Ohlsson, Claes
Islander, Ulrika
Carlsten, Hans
TI Possible role of lymphocytes in glucocorticoid-induced increase in
trabecular bone mineral density
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; POSTMENOPAUSAL WOMEN; ESTROGEN DEFICIENCY;
IN-VIVO; DEXAMETHASONE TREATMENT; CORTICOSTEROID ACTION;
RHEUMATOID-ARTHRITIS; ORAL CORTICOSTEROIDS; JOINT DESTRUCTION;
T-LYMPHOCYTES
AB Treatment with anti-inflammatory glucocorticoids is associated with osteoporosis. Many of the treated patients are postmenopausal women, who even without treatment have an increased risk of osteoporosis. Lymphocytes have been shown to play a role in postmenopausal and arthritis-induced osteoporosis, and they are targeted by glucocorticoids. The aim of this study was to investigate the mechanisms behind effects of glucocorticoids on bone during health and menopause, focusing on lymphocytes. Female C57BL/6 or SCID mice were therefore sham-operated or ovariectomized and 2 weeks later treatment with dexamethasone (dex), the nonsteroidal anti-inflammatory drug carprofen, or vehicle was started and continued for 2.5 weeks. At the termination of experiments, femurs were phenotyped using peripheral quantitative computed tomography and high-resolution micro-computed tomography, and markers of bone turnover were analyzed in serum. Tand B lymphocyte populations in bone marrow and spleen were analyzed by flow cytometry. Dex-treated C57BL/6 mice had increased trabecular bone mineral density, but lower cortical content and thickness compared with vehicle-treated mice. The dex-treated mice also had lower levels of bone turnover markers and markedly decreased numbers of spleen T and B lymphocytes. In contrast, these effects could not be repeated when mice were treated with the nonsteroidal anti-inflammatory drug carprofen. In addition, dex did not increase trabecular bone in ovariectomized SCID mice lacking functional Tand B lymphocytes. In contrast to most literature, the results from this study indicate that treatment with dex increased trabecular bone density, which may indicate that this effect is associated with corticosteroid-induced alterations of the lymphocyte populations.
C1 [Grahnemo, Louise; Jochems, Caroline; Andersson, Annica; Engdahl, Cecilia; Islander, Ulrika; Carlsten, Hans] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Rheumatol & Inflammat, S-40530 Gothenburg, Sweden.
[Grahnemo, Louise; Jochems, Caroline; Andersson, Annica; Engdahl, Cecilia; Islander, Ulrika; Carlsten, Hans] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med & Clin N, S-40530 Gothenburg, Sweden.
[Jochems, Caroline] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Grahnemo, L (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Rheumatol & Inflammat, Box 480, S-40530 Gothenburg, Sweden.
EM louise.grahnemo@gu.se
RI Andersson, Annica/B-4424-2015;
OI Andersson, Annica/0000-0002-3333-8687; Grahnemo,
Louise/0000-0001-5276-6612; Engdahl, Cecilia/0000-0002-8914-0178
FU Medical Faculty of Goteborg University (ALF); Goteborg Medical Society;
King Gustav V's 80 years' Foundation; Sahlgrenska Foundation; NovoNordic
Foundation; Borje Dahlin foundation; Association against Rheumatism;
Reumaforskningsfond Margareta; Swedish Research Council
FX This study was supported by grants from the Medical Faculty of Goteborg
University (ALF), The Goteborg Medical Society, King Gustav V's 80
years' Foundation, the Sahlgrenska Foundation, the NovoNordic
Foundation, the Borje Dahlin foundation, the Association against
Rheumatism, Reumaforskningsfond Margareta, and the Swedish Research
Council. The FACS Canto II was purchased thanks to generous support from
the Inga-Britt and Arne Lundberg Foundation.
NR 53
TC 6
Z9 8
U1 0
U2 4
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
EI 1479-6805
J9 J ENDOCRINOL
JI J. Endocrinol.
PD JAN
PY 2015
VL 224
IS 1
BP 97
EP 108
DI 10.1530/JOE-14-0508
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AY9OW
UT WOS:000347881200012
PM 25359897
ER
PT J
AU Guevara, AB
Demonet, JF
Polejaeva, E
Knutson, KM
Wassermann, EM
Krueger, F
Grafman, J
AF Guevara, Andrea Brioschi
Demonet, Jean-Francois
Polejaeva, Elena
Knutson, Kristine M.
Wassermann, Eric M.
Krueger, Frank
Grafman, Jordan
TI Association Between Long-Term Cognitive Decline in Vietnam Veterans With
TBI and Caregiver Attachment Style
SO JOURNAL OF HEAD TRAUMA REHABILITATION
LA English
DT Article
DE attachment style (AS); caregiver; cognitive reserve; fearful; neural
plasticity; traumatic brain injury (TBI)
ID TRAUMATIC BRAIN-INJURY; PENETRATING HEAD-INJURY; ADULT ATTACHMENT;
SYNAPTIC PLASTICITY; COPING STRATEGIES; FOLLOW-UP; DEMENTIA;
ENVIRONMENT; ENRICHMENT; STABILITY
AB Objective: To examine whether a caregiver's attachment style is associated with patient cognitive trajectory after traumatic brain injury (TBI). Setting: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Participants: Forty Vietnam War veterans with TBI and their caregivers. Main Outcome Measure: Cognitive performance, measured by the Armed Forces Qualification Test percentile score, completed at 2 time points: preinjury and 40 years postinjury. Design: On the basis of caregivers' attachment style (secure, fearful, preoccupied, dismissing), participants with TBI were grouped into a high or low group. To examine the association between cognitive trajectory of participants with TBI and caregivers' attachment style, we ran four 2 x 2 analysis of covariance on cognitive performances. Results: After controlling for other factors, cognitive decline was more pronounced in participants with TBI with a high fearful caregiver than among those with a low fearful caregiver. Other attachment styles were not associated with decline. Conclusion and Implication: Caregiver fearful attachment style is associated with a significant decline in cognitive status after TBI. We interpret this result in the context of the neural plasticity and cognitive reserve literatures. Finally, we discuss its impact on patient demand for healthcare services and potential interventions.
C1 [Guevara, Andrea Brioschi; Polejaeva, Elena; Knutson, Kristine M.; Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA.
[Guevara, Andrea Brioschi; Demonet, Jean-Francois] Univ Lausanne, Fac Biol & Med, Lausanne, VD, Switzerland.
[Demonet, Jean-Francois] Univ Lausanne Hosp, Dept Clin Neurosci, Memory Ctr, CHUV, Lausanne, Switzerland.
[Krueger, Frank] George Mason Univ, Mol Neurosci Dept, Fairfax, VA 22030 USA.
[Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Grafman, Jordan] Rehabil Inst Chicago, Chicago, IL 60611 USA.
RP Grafman, J (reprint author), Rehabil Inst Chicago, 345 E Super St,Ste 1796, Chicago, IL 60611 USA.
EM jgrafman@ric.org
OI Grafman, Jordan H./0000-0001-8645-4457; Demonet,
Jean-Francois/0000-0003-0100-6175
NR 65
TC 1
Z9 1
U1 3
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-9701
EI 1550-509X
J9 J HEAD TRAUMA REHAB
JI J. Head Trauma Rehabil.
PD JAN-FEB
PY 2015
VL 30
IS 1
BP E26
EP E33
DI 10.1097/HTR.0000000000000046
PG 8
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA AY8BW
UT WOS:000347780400004
ER
PT J
AU Nguyen, R
Dombi, E
Akshintala, S
Baldwin, A
Widemann, BC
AF Nguyen, Rosa
Dombi, Eva
Akshintala, Srivandana
Baldwin, Andrea
Widemann, Brigitte C.
TI Characterization of spinal findings in children and adults with
neurofibromatosis type 1 enrolled in a natural history study using
magnetic resonance imaging
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Neurofibromatosis type 1; Plexiform neurofibroma; Spinal MRI; Spinal
neurofibroma
ID MRI; TUMORS; SCOLIOSIS; STENOSIS; AGE
AB To characterize spinal abnormalities in patients with neurofibromatosis type 1 (NF1) using magnetic resonance imaging (MRI). NF1 patients with at least one spine MRI were selected from participants prospectively enrolled in the National Cancer Institute NF1 Natural History Study. Data were analyzed retrospectively. Ninety-seven patients (38 females, median age 14.2 years, standard deviation [SD] 7.6) had baseline imaging of the spine, and 26 patients (27 %) had one follow-up spine MRI (follow up time 2.5 years, SD 1.1, range 0.7-4.7). Seventy-eight patients (80 %) had spinal neurofibromas, with rising frequency from 70 % in patients younger than 10 years to 80 % in patients aged 10-18 years to 89 % in individuals older than 18 years of age. At baseline, 33/97 patients (34 %) had MRI changes consistent with spinal cord compression that was most prevalent at the cervical (43 %) and lumbar spine region (40 %). Seven of nine patients with progression of their spinal neurofibromas developed cord compression. Paraspinal plexiform neurofibromas (PNs) were present in 77/97 patients (79 %), of which 68 patients (88 %) had concomitant spinal neurofibromas. Spinal curvature abnormality was present in 50/97 patients (51 %, 20 females, median age 14.6 years, SD 7.6). Patients with paraspinal PNs had six-fold higher odds of developing spinal curvature abnormalities compared to patients without PN (OR = 5.9, 95 % CI 1.81 to 19.44, p = 0.0033). A total of 58/97 patients (60 %, median age 16.1 years, SD 7.8, range 4.8-48.2 years) presented with neurologic abnormalities that progressed in 12/26 patients (46 %). Substantial spinal neurofibroma and paraspinal PN burden was observed in our study population, which represents a selective group of patients with specifically more severe tumor involvement than the general NF1 population. Occurrence and progression of spinal neurofibromas on repeat evaluations highlight the need for longitudinal clinical monitoring in patients with known spinal disease.
C1 [Nguyen, Rosa] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Nguyen, Rosa] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA.
[Nguyen, Rosa; Dombi, Eva; Akshintala, Srivandana; Baldwin, Andrea; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Nguyen, R (reprint author), St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM rosi.nguyen@gmail.com
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX We thank the patients and their families for participating in the NF1
natural history study and Natasha Brunson for her assistance with the
data management. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 25
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD JAN
PY 2015
VL 121
IS 1
BP 209
EP 215
DI 10.1007/s11060-014-1629-5
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AY9UE
UT WOS:000347895100024
PM 25293439
ER
PT J
AU Romero, R
Miranda, J
Kusanovic, JP
Chaiworapongsa, T
Chaemsaithong, P
Martinez, A
Gotsch, F
Dong, Z
Ahmed, AI
Shaman, M
Lannaman, K
Yoon, BH
Hassan, SS
Kim, CJ
Korzeniewski, SJ
Yeo, LM
Kim, YM
AF Romero, Roberto
Miranda, Jezid
Kusanovic, Juan P.
Chaiworapongsa, Tinnakorn
Chaemsaithong, Piya
Martinez, Alicia
Gotsch, Francesca
Dong, Zhong
Ahmed, Ahmed I.
Shaman, Majid
Lannaman, Kia
Yoon, Bo Hyun
Hassan, Sonia S.
Kim, Chong J.
Korzeniewski, Steven J.
Yeo, Lami
Kim, Yeon Mee
TI Clinical chorioamnionitis at term I: microbiology of the amniotic cavity
using cultivation and molecular techniques
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE funisitis; Gardnerella vaginalis; histologic chorioamnionitis;
intra-amniotic infection/inflammation; microbial invasion of the
amniotic cavity (MIAC); PCR/ESI-MS; pregnancy; sterile inflammation;
ureaplasma urealyticum
ID PRETERM PREMATURE RUPTURE; POLYMERASE-CHAIN-REACTION; FLUID
INTERLEUKIN-6 LEVELS; BLOOD-CELL COUNT; POSTCESAREAN DELIVERY
ENDOMETRITIS; INFLAMMATORY RESPONSE SYNDROME; UREAPLASMA-UREALYTICUM;
INTRAAMNIOTIC INFECTION; MYCOPLASMA-HOMINIS; INTACT MEMBRANES
AB Introduction: The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection.
Methods: The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration = 2.6 ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations.
Results: 1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive for microorganisms in 59% (27/46) - combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2) Ureaplasma urealyticum (n = 8) and Gardnerella vaginalis (n = 10) were the microorganisms most frequently identified by cultivation and PCR/ESI-MS, respectively. 3) When combining the results of AF culture, PCR/ESI-MS and AF IL-6 concentrations, 15% (7/46) of patients did not have intra-amniotic inflammation or infection, 6.5% (3/46) had only MIAC, 54% (25/46) had microbial-associated intra-amniotic inflammation, and 24% (11/46) had intra-amniotic inflammation without detectable microorganisms. 4) Placental lesions consistent with acute AF infection were significantly more frequent in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [70.8% (17/24) vs. 28.6% (2/7); P = 0.04].
Conclusion: Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.
C1 [Miranda, Jezid; Kusanovic, Juan P.; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Martinez, Alicia; Gotsch, Francesca; Dong, Zhong; Ahmed, Ahmed I.; Shaman, Majid; Lannaman, Kia; Hassan, Sonia S.; Kim, Chong J.; Korzeniewski, Steven J.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Bethesda, MD USA.
[Miranda, Jezid; Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Martinez, Alicia; Dong, Zhong; Ahmed, Ahmed I.; Shaman, Majid; Lannaman, Kia; Hassan, Sonia S.; Korzeniewski, Steven J.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Kusanovic, Juan P.] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, Santiago, Chile.
[Kusanovic, Juan P.] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile.
[Chaiworapongsa, Tinnakorn; Gotsch, Francesca; Hassan, Sonia S.; Kim, Chong J.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Program Perinatal Res & Obstet, Div Intramural Res,NIH, Detroit, MI USA.
[Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Yeo, Lami] Hutzel Womens Hosp, Detroit Med Ctr, Detroit, MI USA.
[Gotsch, Francesca] Azienda Osped Univ, Integrata Verona, Verona, Italy.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Kim, Chong J.] Univ Ulsan, Coll Med, Dept Pathol, Asan Med Ctr, Seoul, South Korea.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov; ykim.haeundae@gmail.com
NR 229
TC 26
Z9 27
U1 0
U2 9
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
EI 1619-3997
J9 J PERINAT MED
JI J. Perinat. Med.
PD JAN
PY 2015
VL 43
IS 1
BP 19
EP 36
DI 10.1515/jpm-2014-0249
PG 18
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA AZ0TN
UT WOS:000347957900004
PM 25720095
ER
PT J
AU Solomon, SS
Mehta, SH
SriKrishnan, AK
Solomon, S
McFall, AM
Laeyendecker, O
Celentano, DD
Iqbal, SH
Anand, S
Vasudevan, CK
Saravanan, S
Lucas, GM
Kumar, MS
Sulkowski, MS
Quinn, TC
AF Solomon, Sunil Suhas
Mehta, Shruti H.
SriKrishnan, Aylur K.
Solomon, Suniti
McFall, Allison M.
Laeyendecker, Oliver
Celentano, David D.
Iqbal, Syed H.
Anand, Santhanam
Vasudevan, Canjeevaram K.
Saravanan, Shanmugam
Lucas, Gregory M.
Kumar, Muniratnam S.
Sulkowski, Mark S.
Quinn, Thomas C.
TI Burden of hepatitis C virus disease and access to hepatitis C virus
services in people who inject drugs in India: a cross-sectional study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID UNITED-STATES; ANTIVIRAL THERAPY; HCV INFECTION; SOFOSBUVIR; USERS;
EPIDEMIOLOGY; PREVALENCE; PREVENTION; MORTALITY; BARRIERS
AB Background 90% of individuals infected with hepatitis C virus (HCV) worldwide reside in resource-limited settings. We aimed to characterise the prevalence of HCV, HIV/HCV co-infection, and the HCV care continuum in people who inject drugs in India.
Methods 14 481 people (including 31 seeds individuals selected as the starting point for sampling because they were well connected in the drug using community) who inject drugs were sampled from 15 cities throughout India using respondent-driven sampling from Jan 2, 2013 to Dec 19, 2013. Data from seeds were excluded from all analyses. HCV prevalence was estimated by the presence of anti-HCV antibodies incorporating respondent-driven sampling weights. HCV care continuum outcomes were self-reported except for viral clearance in treatment-experienced participants.
Findings The median age of participants was 30 years (IQR 24-36) and 13 608 (92.4%) of 14 449 were men (data were missing for some variables). Weighted HCV prevalence was 5777 (37.2%) of 14447; HIV/HCV co-infection prevalence was 2085 (13-2%) of 14435. Correlates of HCV infection included high lifetime injection frequency, HIV positivity, and a high prevalence of people with HIV RNA (more than 1000 copies per mL) in the community. Of the 5777 people who inject drugs that were HCV antibody positive, 440 (5.5%) were aware of their status, 225 (3.0%) had seen a doctor for their HCV, 79 (1.4%) had taken HCV treatment, and 18 (0.4%) had undetectable HCV RNA. Of 12 128 participants who had not previously been tested for HCV, 6138 (50.5%) did not get tested because they had not heard of HCV. In the 5777 people who were HCV antibody positive, 2086 (34.4%) reported harmful or hazardous alcohol use, of whom 1082 (50.4%) were dependent, and 3821 (65.3%) reported needle sharing. Awareness of HCV positive status was significantly associated with higher education, HIV testing history, awareness of HIV positive status, and higher community antiretroviral therapy coverage.
Interpretation The high burden of HCV and HIV/HCV co-infection coupled with low-access to HCV services emphasises an urgent need to include resource-limited settings in the global HCV agenda. Although new treatments will become available worldwide in the near future, programmes to improve awareness and reduce disease progression and transmission need to be scaled up without further delay. Failure to do so could result in patterns of rising mortality, undermining advances in survival attributed to widespread HIV treatment.
C1 [Solomon, Sunil Suhas; Laeyendecker, Oliver; Lucas, Gregory M.; Sulkowski, Mark S.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Solomon, Sunil Suhas; Mehta, Shruti H.; McFall, Allison M.; Celentano, David D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Solomon, Sunil Suhas; SriKrishnan, Aylur K.; Solomon, Suniti; Iqbal, Syed H.; Anand, Santhanam; Vasudevan, Canjeevaram K.; Saravanan, Shanmugam; Kumar, Muniratnam S.] YR Gaitonde Ctr AIDS Res & Educ, Madras, Tamil Nadu, India.
[Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Solomon, SS (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
EM sss@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU US National Institutes of Health
FX Funding 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 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JAN
PY 2015
VL 15
IS 1
BP 36
EP 45
DI 10.1016/S1473-3099(14)71045-X
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA AY9GD
UT WOS:000347857900026
PM 25486851
ER
PT J
AU Checkley, W
White, AC
Jaganath, D
Arrowood, MJ
Chalmers, RM
Chen, XM
Fayer, R
Griffiths, JK
Guerrant, RL
Hedstrom, L
Huston, CD
Kotloff, KL
Kang, G
Mead, JR
Miller, M
Petri, WA
Priest, JW
Roos, DS
Striepen, B
Thompson, RCA
Ward, HD
Van Voorhis, WA
Xiao, LH
Zhu, G
Houpt, ER
AF Checkley, William
White, A. Clinton, Jr.
Jaganath, Devon
Arrowood, Michael J.
Chalmers, Rachel M.
Chen, Xian-Ming
Fayer, Ronald
Griffiths, Jeffrey K.
Guerrant, Richard L.
Hedstrom, Lizbeth
Huston, Christopher D.
Kotloff, Karen L.
Kang, Gagandeep
Mead, Jan R.
Miller, Mark
Petri, William A., Jr.
Priest, Jeffrey W.
Roos, David S.
Striepen, Boris
Thompson, R. C. Andrew
Ward, Honorine D.
Van Voorhis, Wesley A.
Xiao, Lihua
Zhu, Guan
Houpt, Eric R.
TI A review of the global burden, novel diagnostics, therapeutics, and
vaccine targets for cryptosporidium
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID INOSINE 5'-MONOPHOSPHATE DEHYDROGENASE;
ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SYSTEMIC ANTIBODY-RESPONSES;
INTESTINAL EPITHELIAL-CELLS; RANDOMIZED CONTROLLED-TRIAL;
EARLY-CHILDHOOD DIARRHEA; MANNOSE-BINDING LECTIN; NATURAL-KILLER-CELLS;
TIME PCR DETECTION; PARVUM INFECTION
AB Cryptosporidium spp are well recognised as causes of diarrhoeal disease during waterborne epidemics and in immunocompromised hosts. Studies have also drawn attention to an underestimated global burden and suggest major gaps in optimum diagnosis, treatment, and immunisation. Cryptosporidiosis is increasingly identified as an important cause of morbidity and mortality worldwide. Studies in low-resource settings and high-income countries have confirmed the importance of cryptosporidium as a cause of diarrhoea and childhood malnutrition. Diagnostic tests for cryptosporidium infection are suboptimum, necessitating specialised tests that are often insensitive. Antigen-detection and PCR improve sensitivity, and multiplexed antigen detection and molecular assays are underused. Therapy has some effect in healthy hosts and no proven efficacy in patients with AIDS. Use of cryptosporidium genomes has helped to identify promising therapeutic targets, and drugs are in development, but methods to assess the efficacy in vitro and in animals are not well standardised. Partial immunity after exposure suggests the potential for successful vaccines, and several are in development; however, surrogates of protection are not well defined. Improved methods for propagation and genetic manipulation of the organism would be significant advances.
C1 [Checkley, William; Jaganath, Devon] Johns Hopkins Univ, Dept Int Hlth, Program Global Dis Epidemiol & Control, Baltimore, MD USA.
[Checkley, William; Miller, Mark] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[White, A. Clinton, Jr.] Univ Texas Med Branch, Div Infect Dis, Galveston, TX 77555 USA.
[Arrowood, Michael J.; Priest, Jeffrey W.; Xiao, Lihua] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Chalmers, Rachel M.] Publ Hlth Wales, Natl Cryptosporidium Reference Unit, Swansea, W Glam, Wales.
[Chen, Xian-Ming] Creighton Univ, Dept Med Microbiol & Immunol, Omaha, NE 68178 USA.
[Fayer, Ronald] USDA, Environm Microbial Food Safety Lab, Beltsville, MD 20705 USA.
[Griffiths, Jeffrey K.] Tufts Univ, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
[Guerrant, Richard L.; Petri, William A., Jr.; Houpt, Eric R.] Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA USA.
[Hedstrom, Lizbeth] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA.
[Hedstrom, Lizbeth] Brandeis Univ, Dept Chem, Waltham, MA 02254 USA.
[Huston, Christopher D.] Univ Vermont, Div Infect Dis, Burlington, VT USA.
[Kotloff, Karen L.] Univ Maryland, Sch Med, Div Infect Dis & Trop Pediat, Dept Pediat,Ctr Vaccine Dev, Baltimore, MD 21201 USA.
[Kang, Gagandeep] Christian Med Coll & Hosp, Div Gastrointestinal Sci, Vellore, Tamil Nadu, India.
[Mead, Jan R.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Mead, Jan R.] Atlanta VA Med Ctr, Decatur, GA USA.
[Roos, David S.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
[Striepen, Boris] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA.
[Thompson, R. C. Andrew] Murdoch Univ, Sch Vet & Life Sci, Perth, WA, Australia.
[Ward, Honorine D.] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA USA.
[Van Voorhis, Wesley A.] Univ Washington, Dept Med, Allergy & Infect Dis Div, Seattle, WA USA.
[Van Voorhis, Wesley A.] Univ Washington, Allergy & Infect Dis Div, Dept Global Hlth, Seattle, WA 98195 USA.
[Van Voorhis, Wesley A.] Univ Washington, Dept Microbiol, Allergy & Infect Dis Div, Seattle, WA 98195 USA.
[Zhu, Guan] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA.
RP Checkley, W (reprint author), Johns Hopkins Univ, Sch Med, Suite 9121,1800 Orleans Ave, Baltimore, MD 21205 USA.
EM wcheckl1@jhmi.edu
RI Xiao, Lihua/B-1704-2013;
OI Xiao, Lihua/0000-0001-8532-2727; White, A Clinton/0000-0002-9668-4632;
Striepen, Boris/0000-0002-7426-432X
FU Bill & Melinda Gates Foundation
FX We acknowledge all speakers who attended the meeting Cryptosporidium:
Global Burden, Novel Diagnostics, Therapeutics and Vaccine Targets, held
in Philadelphia, PA, USA, in December, 2011. We received financial
support from the Bill & Melinda Gates Foundation; our funding source did
not have a role in the development of this Review. The findings and
conclusions in this Review are those of the authors and do not
necessarily represent the official position of the Centers for Disease
Control and Prevention.
NR 148
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U2 64
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JAN
PY 2015
VL 15
IS 1
BP 85
EP 94
DI 10.1016/S1473-3099(14)70772-8
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA AY9GD
UT WOS:000347857900031
PM 25278220
ER
PT J
AU Rosean, TR
Tompkins, VS
Olivier, AK
Sompallae, R
Norian, LA
Morse, HC
Waldschmidt, TJ
Janz, S
AF Rosean, T. R.
Tompkins, V. S.
Olivier, A. K.
Sompallae, R.
Norian, L. A.
Morse, H. C., III
Waldschmidt, T. J.
Janz, S.
TI The tumor microenvironment is the main source of IL-6 for plasma cell
tumor development in mice
SO LEUKEMIA
LA English
DT Letter
ID BONE-MARROW MICROENVIRONMENT; MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY;
PLASMACYTOMAS; INTERLEUKIN-6; INHIBITION; MYC
C1 [Rosean, T. R.; Norian, L. A.; Waldschmidt, T. J.; Janz, S.] Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA.
[Tompkins, V. S.; Olivier, A. K.; Sompallae, R.; Waldschmidt, T. J.; Janz, S.] UI Carver Coll Med, Dept Pathol, Iowa City, IA USA.
[Sompallae, R.] UI Carver Coll Med, Bioinformat Core Facil, Iowa City, IA USA.
[Norian, L. A.] UI Carver Coll Med, Dept Urol, Iowa City, IA USA.
[Morse, H. C., III] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Rosean, TR (reprint author), Univ Iowa, Interdisciplinary Grad Program Immunol, Iowa City, IA 52242 USA.
EM siegfried-janz@uiowa.edu
OI Tompkins, Van/0000-0003-1279-8075
FU NCI NIH HHS [P30 CA086862, P30CA086862, P50 CA097274, P50CA097274, R01
CA151354, R01CA151354]; NHLBI NIH HHS [T32 HL007344]; NIAID NIH HHS [T32
AI007485, 5T32 AI007485]
NR 15
TC 10
Z9 10
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD JAN
PY 2015
VL 29
IS 1
BP 233
EP 237
DI 10.1038/leu.2014.260
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA AY6JX
UT WOS:000347673700026
PM 25257990
ER
PT J
AU Tomei, S
Bedognetti, D
De Giorgi, V
Sommariva, M
Civini, S
Reinboth, J
Al Hashmi, M
Ascierto, ML
Liu, QZ
Ayotte, BD
Worschech, A
Uccellini, L
Ascierto, PA
Stroncek, D
Palmieri, G
Chouchane, L
Wang, E
Marincola, FM
AF Tomei, Sara
Bedognetti, Davide
De Giorgi, Valeria
Sommariva, Michele
Civini, Sara
Reinboth, Jennifer
Al Hashmi, Muna
Ascierto, Maria Libera
Liu, Qiuzhen
Ayotte, Ben D.
Worschech, Andrea
Uccellini, Lorenzo
Ascierto, Paolo A.
Stroncek, David
Palmieri, Giuseppe
Chouchane, Lotfi
Wang, Ena
Marincola, Francesco M.
TI The immune-related role of BRAF in melanoma
SO MOLECULAR ONCOLOGY
LA English
DT Article
DE BRAF; NRAS; Melanoma; Immune phenotype
ID PROTEIN-KINASE ACTIVATION; GENE-EXPRESSION SIGNATURE; N-RAS ONCOGENE;
METASTATIC MELANOMA; TARGETED THERAPY; B-RAF; CANCER-IMMUNOTHERAPY;
CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; SIGNALING PATHWAY
AB Background: The existence of a dichotomy between immunologically active and quiescent tumor phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. BRAF and NAAS mutations are commonly acquired during melanoma progression. Here we explored the role of BRAP and NRAS mutations in influencing the immune phenotype based on a classification previously identified by our group.
Methods: One-hundred-thirteen melanoma metastases underwent microarray analysis and BRAF and NRAS genotyping. Allele-specific PCR was also performed in order to exclude low-frequency mutations.
Results: Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy,such association was stronger in samples displaying low BRAY mRNA expression. However, when testing NAAS mutations, we were not able to find the same association.
Conclusion: This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of Federation of European Biochemical Societies. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
C1 [Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Sommariva, Michele; Reinboth, Jennifer; Ascierto, Maria Libera; Liu, Qiuzhen; Uccellini, Lorenzo; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Sommariva, Michele; Reinboth, Jennifer; Ascierto, Maria Libera; Liu, Qiuzhen; Uccellini, Lorenzo; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Tomei, Sara; Worschech, Andrea; Chouchane, Lotfi] Weill Cornell Med Coll Qatar, Dept Genet Med, Doha, Qatar.
[Tomei, Sara; Bedognetti, Davide; Al Hashmi, Muna; Wang, Ena; Marincola, Francesco M.] Sidra Med & Res Ctr, Doha, Qatar.
[Sommariva, Michele] Univ Milan, Dept Biomed Sci & Hlth, Milan, Italy.
[Civini, Sara; Stroncek, David] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Civini, Sara; Stroncek, David] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Reinboth, Jennifer] Univ Wurzburg, Dept Biochem, Bioctr, D-97074 Wurzburg, Germany.
[Reinboth, Jennifer] Genelux Corp, San Diego Sci Ctr, San Diego, CA 92109 USA.
[Ascierto, Maria Libera] Univ Genoa, CEBR, I-16126 Genoa, Italy.
[Ayotte, Ben D.] No Michigan Univ, Dept Biol, Marquette, MI 49855 USA.
[Uccellini, Lorenzo] Univ Milan, Inst Infect & Trop Dis, L Sacco Hosp, Milan, Italy.
[Ascierto, Paolo A.] Ist Nazl Tumori Fdn G Pascale, Naples, Italy.
[Palmieri, Giuseppe] CNR, Inst Biomol Chem, Sassari, Italy.
RP Tomei, S (reprint author), Qatar Fdn, Sidra Med & Res Ctr, Al Nasr Tower,Al Corniche St,PO 26999, Doha, Qatar.
EM stomei@sidra.org
RI De Giorgi, Valeria/D-4582-2017; Sommariva, Michele/C-1174-2017
OI Bedognetti, Davide/0000-0002-5857-773X; Palmieri,
Giuseppe/0000-0002-4350-2276; Sommariva, Michele/0000-0002-7622-0996
FU Intramural Research Program of the National Institutes of Health (NIH);
Fondazione Melanoma Onlus, Naples, Italy; Sidra Medical and Research
Center, Doha, Qatar
FX This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH); all NIH affiliated authors
performed this work as part of their official duties. The study was
supported in part by Fondazione Melanoma Onlus, Naples, Italy and Sidra
Medical and Research Center, Doha, Qatar.
NR 55
TC 10
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U2 5
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 JAN
PY 2015
VL 9
IS 1
BP 93
EP 104
DI 10.1016/j.molonc.2014.07.014
PG 12
WC Oncology
SC Oncology
GA AY9IL
UT WOS:000347863700008
PM 25174651
ER
PT J
AU Fratta, P
Polke, JM
Newcombe, J
Mizielinska, S
Lashley, T
Poulter, M
Beck, J
Preza, E
Devoy, A
Sidle, K
Howard, R
Malaspina, A
Orrell, RW
Clarke, J
Lu, CH
Mokj, K
Collins, T
Shoaii, M
Nanji, T
Wray, S
Adamson, G
Pittman, A
Renton, AE
Traynor, BJ
Sweeney, MG
Revesz, T
Houlden, H
Mead, S
Isaacs, AM
Fisher, EMC
AF Fratta, Pietro
Polke, James M.
Newcombe, Jia
Mizielinska, Sarah
Lashley, Tammaryn
Poulter, Mark
Beck, Jon
Preza, Elisavet
Devoy, Anny
Sidle, Katie
Howard, Robin
Malaspina, Andrea
Orrell, Richard W.
Clarke, Jan
Lu, Ching-Hua
Mok, Kin
Collins, Toby
Shoaii, Maryam
Nanji, Tina
Wray, Selina
Adamson, Gary
Pittman, Alan
Renton, Alan E.
Traynor, Bryan J.
Sweeney, Mary G.
Revesz, Tamas
Houlden, Henry
Mead, Simon
Isaacs, Adrian M.
Fisher, Elizabeth M. C.
TI Screening a UK amyotrophic lateral sclerosis cohort provides evidence of
multiple origins of the C9orf72 expansion
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Frontotemporal dementia; Somatic instability; Amyotrophic lateral
sclerosis
ID FRONTOTEMPORAL LOBAR DEGENERATION; HEXANUCLEOTIDE REPEAT EXPANSIONS;
DEMENTIA; MUTATION; ALS; DISEASE; FTD; FREQUENT; RNA
AB An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0-30 hexanucleotide repeats are present in the general population, expansions > 500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50-200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD. (C) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Fratta, Pietro; Mizielinska, Sarah; Poulter, Mark; Beck, Jon; Devoy, Anny; Collins, Toby; Adamson, Gary; Mead, Simon; Isaacs, Adrian M.; Fisher, Elizabeth M. C.] UCL, Dept Neurodegenerat Dis, London WC1N 3BG, England.
[Fratta, Pietro; Orrell, Richard W.; Fisher, Elizabeth M. C.] UCL, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England.
[Polke, James M.; Nanji, Tina; Sweeney, Mary G.; Houlden, Henry] Neurogenet Unit, London, England.
[Newcombe, Jia] UCL, Inst Neurol, NeuroResource, London WC1N 3BG, England.
[Lashley, Tammaryn; Revesz, Tamas] UCL, Queen Sq Brain Bank Neurol Disorders, London WC1N 3BG, England.
[Poulter, Mark; Beck, Jon; Adamson, Gary] UCL, MRC Prion Unit, London WC1N 3BG, England.
[Preza, Elisavet; Sidle, Katie; Orrell, Richard W.; Shoaii, Maryam; Wray, Selina; Pittman, Alan; Houlden, Henry] UCL, Dept Mol Neurosci, London WC1N 3BG, England.
[Sidle, Katie; Howard, Robin; Malaspina, Andrea; Orrell, Richard W.; Clarke, Jan] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England.
[Lu, Ching-Hua] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, Ctr Neurosci & Trauma, London, England.
[Lu, Ching-Hua; Mok, Kin] UCL, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
[Renton, Alan E.; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Fratta, P (reprint author), UCL, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England.
EM p.fratta@ucl.ac.uk; James.Polke@uclh.nhs.uk; e.fisher@prion.ucl.ac.uk
RI Pittman, Alan/D-6231-2012; Lashley, Tammaryn/D-2583-2009; Mok,
Kin/F-5860-2012; Houlden, Henry/C-1532-2008; Revesz, Tamas/A-8732-2010;
OI Houlden, Henry/0000-0002-2866-7777; Revesz, Tamas/0000-0003-2501-0259;
Devoy, Anny/0000-0002-1293-0630; Wray, Selina/0000-0003-3062-7050
FU Medical Research Council; Medical Research Council/Motor Neurone Disease
Association LEW Fellowship; NIHR-UCLH-Biomedical Research Centre;
Thierry Latran Foundation; Motor Neurone Disease Association; Department
of Health's National Institute for Health Research Biomedical Research
Centres funding scheme; Alzheimer's Research Fellowship
FX This work was supported by the Medical Research Council (Mark Poulter,
Simon Mead, and Elizabeth M. C. FIsher), Medical Research Council/Motor
Neurone Disease Association LEW Fellowship (Pietro Fratta),
NIHR-UCLH-Biomedical Research Centre (Pietro Fratta), Thierry Latran
Foundation (Elizabeth Fisher), Motor Neurone Disease Association (Adrian
M. Isaacs, Elizabeth Fisher, and Richard Orrell). Part of this work was
undertaken at University College London Hospitals/University College
London, which received a proportion of funding from the Department of
Health's National Institute for Health Research Biomedical Research
Centres funding scheme. Tammaryn Lashley is funded by an Alzheimer's
Research Fellowship.
NR 33
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JAN
PY 2015
VL 36
IS 1
AR 546.e1
DI 10.1016/j.neurobiolaging.2014.07.037
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AY2HD
UT WOS:000347408600059
PM 25179228
ER
PT J
AU Ghani, M
Lang, AE
Zinman, L
Nacmias, B
Sorbi, S
Bessi, V
Tedde, A
Tartaglia, MC
Surace, EI
Sato, C
Moreno, D
Xi, ZR
Hung, R
Nalls, MA
Singleton, A
St George-Hyslop, P
Rogaeva, E
AF Ghani, Mahdi
Lang, Anthony E.
Zinman, Lorne
Nacmias, Benedetta
Sorbi, Sandro
Bessi, Valentina
Tedde, Andrea
Tartaglia, Maria Carmela
Surace, Ezequiel I.
Sato, Christine
Moreno, Danielle
Xi, Zhengrui
Hung, Rachel
Nalls, Mike A.
Singleton, Andrew
St George-Hyslop, Peter
Rogaeva, Ekaterina
TI Mutation analysis of patients with neurodegenerative disorders using
NeuroX array
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE NeuroX; Mutation; Neurodegenerative disorder
ID ONSET ALZHEIMERS-DISEASE; AMYOTROPHIC-LATERAL-SCLEROSIS;
PARKINSONS-DISEASE; GENE-MUTATIONS; SOD1 MUTATION; ASSOCIATION;
PHENOTYPE; VARIANTS; GENOME; TREM2
AB Genetic analyses of patients with neurodegenerative disorders have identified multiple genes that need to be investigated for the presence of damaging variants. However, mutation analysis by Sanger sequencing is costly and time consuming. We tested the utility of a recently designed semi-custom genome-wide array (NeuroX; Illumina, Inc) tailored to study neurodegenerative diseases (e. g., mutation screening). We investigated 192 patients with 4 different neurodegenerative disorders for the presence of rare damaging variations in 77 genes implicated in these diseases. Several causative mutations were identified and confirmed by Sanger sequencing, including PSEN1 p. M233T responsible for Alzheimer's disease in a large Italian family, as well as SOD1 p. A4V and p. I113T in patients with amyotrophic lateral sclerosis. In total, we identified 78 potentially damaging rare variants (frequency < 1%), including ABCA7 p. L400V in a family with Alzheimer's disease and LRRK2 p. R1514Q in 6 of 98 patients with Parkinson's disease (6.1%). In conclusion, NeuroX appears to be helpful for rapid and accurate mutation screening, although further development may be still required to improve some current caveats. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Ghani, Mahdi; Lang, Anthony E.; Tartaglia, Maria Carmela; Sato, Christine; Moreno, Danielle; Xi, Zhengrui; Hung, Rachel; St George-Hyslop, Peter; Rogaeva, Ekaterina] Univ Toronto, Tanz Ctr Neurodegenerat Dis, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Univ Toronto, Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Univ Toronto, Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.; Zinman, Lorne; Tartaglia, Maria Carmela; St George-Hyslop, Peter; Rogaeva, Ekaterina] Univ Toronto, Dept Med, Div Neurol, Toronto, ON M5T 2S8, Canada.
[Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Nacmias, Benedetta; Sorbi, Sandro; Bessi, Valentina; Tedde, Andrea] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Florence, Italy.
[Surace, Ezequiel I.] Consejo Nacl Invest Cient & Tecn CONICET, Mol Biol Lab, Inst Invest Neurol Dr Raul Carrea FLENI, Buenos Aires, DF, Argentina.
[Nalls, Mike A.; Singleton, Andrew] NIH, Neurogenet Lab, Bethesda, MD 20892 USA.
[St George-Hyslop, Peter] Univ Cambridge, Cambridge Inst Med Res, Dept Clin Neurosci, Cambridge, England.
RP St George-Hyslop, P (reprint author), Univ Toronto, Tanz Ctr Neurodegenerat Dis, 60 Leonard Ave, Toronto, ON M5T 2S8, Canada.
EM p.hyslop@utoronto.ca; ekaterina.rogaeva@utoronto.ca
RI Singleton, Andrew/C-3010-2009;
OI NACMIAS, Benedetta/0000-0001-9338-9040; sorbi,
sandro/0000-0002-0380-6670
FU Canadian Institutes of Health Research; Ontario Research Fund; W.
Garfield Weston Foundation; Intramural Research Program of the National
Institute on Aging; National Institutes of Health (NIH), part of the
Department of Health and Human Services [ZO1 AG000958-11]; Cassa di
Risparmio di Pistoia e Pescia [CRPT 2013/0347]; Cassa di Risparmio di
Firenze [CRF 2013/0199]; Ministry of Health [RF-2010-2319722]; PRIN
[2010PWNJXK]
FX This work was supported by grants from the Canadian Institutes of Health
Research, Ontario Research Fund, the W. Garfield Weston Foundation
(Ekaterina Rogaeva and Peter St George-Hyslop); the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health (NIH), part of the Department of Health and Human Services;
project number ZO1 AG000958-11 (Andrew Singleton); the Cassa di
Risparmio di Pistoia e Pescia # CRPT 2013/0347, the Cassa di Risparmio
di Firenze # CRF 2013/0199, Ministry of Health # RF-2010-2319722 and #
PRIN 2010PWNJXK (Benedetta Nacmias and Sandro Sorbi).
NR 40
TC 5
Z9 5
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD JAN
PY 2015
VL 36
IS 1
DI 10.1016/j.neurobiolaging.2014.07.038
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA AY2HD
UT WOS:000347408600058
ER
PT J
AU Massey, SH
Estabrook, R
O'Brien, TC
Pine, DS
Burns, JL
Jacob, S
Cook, EH
Wakschlag, LS
AF Massey, Suena H.
Estabrook, Ryne
O'Brien, T. Caitlin
Pine, Daniel S.
Burns, James L.
Jacob, Suma
Cook, Edwin H.
Wakschlag, Lauren S.
TI Preliminary evidence for the interaction of the oxytocin receptor gene
(oxtr) and face processing in differentiating prenatal smoking patterns
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Pregnancy smoking; Oxytocin receptor gene; Social cognition; Nonverbal
accuracy; Cognitive empathy; Differential susceptibility
ID MATERNAL SMOKING; FACIAL EXPRESSIONS; PREGNANCY SMOKING; LUNG-FUNCTION;
METAANALYSIS; CESSATION; BEHAVIOR; PSYCHOPATHOLOGY; SUSCEPTIBILITY;
POLYMORPHISM
AB Prenatal smoking cessation has been described as an empathic action "for the baby," but this has not been empirically demonstrated. We capitalized on a genetically-characterized extant dataset with outstanding measurement of prenatal smoking patterns and maternal face processing data (as an indicator of empathy) to test this hypothesis, and explore how empathy and smoking patterns may be moderated by a genetic substrate of empathy, the oxytocin receptor gene (OXTR). Participants were 143Caucasian women from the East Boston family study with repeated prospective reports of smoking level, adjusted based on repeated cotinine bioassays. Salivary DNA and face processing (Diagnostic Analysis of Nonverbal Accuracy-2) were assessed 14 years later at an adolescent follow-up of offspring. Two-thirds of participants reported smoking prior to pregnancy recognition. Of these, 21% quit during pregnancy; 56% reduced smoking, and 22% smoked persistently at the same level. A significant interaction between face processing and OXTR variants previously associated with increased sensitivity to social context, rs53576GG and rs2254298A, was found (beta =-.181; p =.015); greater ability to identify distress in others was associated with lower levels of smoking during pregnancy for rs53576(GG)/rs2254298(A) individuals (p = .013), but not for other genotypes (p = .892). Testing this "empathy hypothesis of prenatal smoking cessation" in larger studies designed to examine this question can elucidate whether interventions to enhance empathy can improve prenatal smoking cessation rates. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Massey, Suena H.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA.
[Massey, Suena H.; Estabrook, Ryne; Burns, James L.; Wakschlag, Lauren S.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[O'Brien, T. Caitlin] Illinois Coll, Dept Psychol, Jacksonville, IL 62650 USA.
[Pine, Daniel S.] NIMH, Lab Affect & Dev Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
[Jacob, Suma] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55454 USA.
[Cook, Edwin H.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
[Wakschlag, Lauren S.] Northwestern Univ, Inst Policy Res, Evanston, IL 60208 USA.
RP Massey, SH (reprint author), 676 North St Clair St,Suite 1000, Chicago, IL 60611 USA.
EM suena.massey@northwestern.edu; restabrook@northwestern.edu;
tcobrien@northwestern.edu; pined@mail.nih.gov;
james-l-burns@northwestern.edu; sjacob@umn.edu; edcook@uic.edu;
lauriew@northwestern.edu
OI Cook, Edwin/0000-0002-5848-5114; Jacob, Suma/0000-0001-7434-7398
FU National Institute on Drug Abuse (NIDA) [R01 DA015223, R01
DA023653-01A2, R01 DA023653-03S1]; Walden & Jean Young Shaw Foundation;
Northwestern Memorial Foundation
FX Work was supported by grants R01 DA015223, R01 DA023653-01A2, and R01
DA023653-03S1 from the National Institute on Drug Abuse (NIDA) (PI:
Lauren Wakschlag), the Walden & Jean Young Shaw Foundation (PI: Lauren
Wakschlag), and the Northwestern Memorial Foundation (PI: Suena Massey).
Funding sources had no role in the design, collection, analysis or
interpretation of data, writing the manuscript, or the decision to
submit results for publication. We are deeply appreciative of the
expertise provided by Vanja Dukic, PhD, and Kate Pickett, PhD, and
editorial assistance by Stephanie Schuette, BA.
NR 46
TC 5
Z9 5
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
EI 1872-7972
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD JAN 1
PY 2015
VL 584
BP 259
EP 264
DI 10.1016/j.neulet.2014.10.049
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA AY4XS
UT WOS:000347579000049
PM 25450139
ER
PT J
AU Raineri, M
Gonzalez, B
Rivero-Echeto, C
Muniz, JA
Gutierrez, ML
Ghanem, CI
Cadet, JL
Garcia-Rill, E
Urbano, FJ
Bisagno, V
AF Raineri, Mariana
Gonzalez, Betina
Rivero-Echeto, Celeste
Muniz, Javier A.
Laura Gutierrez, Maria
Ghanem, Carolina I.
Cadet, Jean Lud
Garcia-Rill, Edgar
Urbano, Francisco J.
Bisagno, Veronica
TI Differential Effects of Environment-Induced Changes in Body Temperature
on Modafinil's Actions Against Methamphetamine-Induced Striatal Toxicity
in Mice
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Modafinil; Methamphetamine; Dopamine; Astroglia; Striatum; Toxicity
ID INDUCED DOPAMINERGIC NEUROTOXICITY; SUBSTANCE USE DISORDERS; SUBSTITUTED
AMPHETAMINES; CAUDATE-PUTAMEN; C57BL/6J MOUSE; NULL MUTATION; RAT
STRIATUM; IN-VIVO; BRAIN; TRANSPORTER
AB Methamphetamine (METH) exposure can produce hyperthermia that might lead to toxicity and death. Modafinil is a wake-promoting compound that is also been prescribed off-label to treat METH dependence. Modafinil has shown neuroprotective properties against METH harmful effects in animal models. The goal of the present study was to test if the prevention of hyperthermia might play a role on the neuroprotective actions of modafinil against METH toxicity using various ambient temperatures. METH was administered to female C57BL/6 mice in a binge regimen: 4 x 5 mg/kg, 2 h apart; modafinil (90 mg/kg) was injected twice, 1 h before first and fourth METH injections. Drugs were given at cold ambient temperature (14 A degrees C) or hot ambient temperature (29 A degrees C). Body temperature was measured during treatments. Brains were dissected out 6 days after treatments and processed for tyrosine hydroxylase (TH), dopamine transporter (DAT), GFAP and c-Fos immunohistochemistry. Exposure to hot ambient temperature exacerbated METH toxicity evidenced by striatal reductions in TH and DAT and increased GFAP immmunoreactivity. Modafinil counteracted reductions in TH and DAT, but failed to block astroglial activation. At both ambient temperatures tested modafinil did induce increments in GFAP, but the magnitude was significantly lower than the one induced by METH. Both drugs induced increases in c-Fos positive nuclei; modafinil did not block this effect. Our results suggest that protective effects of modafinil against METH-induced neurotoxicity may be dependent, in part, to its hypothermic effects. Nevertheless, modafinil maintained some protective properties on METH-induced alterations in the striatum at different ambient temperatures.
C1 [Raineri, Mariana; Gonzalez, Betina; Muniz, Javier A.; Laura Gutierrez, Maria; Ghanem, Carolina I.; Bisagno, Veronica] Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn ININFA UBA CONIC, Inst Invest Farmacol, RA-1113 Buenos Aires, DF, Argentina.
[Rivero-Echeto, Celeste; Urbano, Francisco J.] Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn, Inst Fisiol Biol Mol & Neurociencias, Lab Fisiol & Biol Mol, RA-1113 Buenos Aires, DF, Argentina.
[Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, NIH, Intramural Res Program, Baltimore, MD USA.
[Garcia-Rill, Edgar] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Ctr Translat Neurosci, Little Rock, AR 72205 USA.
RP Bisagno, V (reprint author), Univ Buenos Aires, Consejo Nacl Invest Cient & Tecn ININFA UBA CONIC, Inst Invest Farmacol, Junin 956,Piso 5, RA-1113 Buenos Aires, DF, Argentina.
EM vbisagno@ffyb.uba.ar
OI Garcia-Rill, Edgar/0000-0003-1367-3071
FU Fundacion Bunge y Born; PIP, Argentina [11420100100072]; PICT, Argentina
[2012-0924, 2012-1769]; NIH [P20 GM103425, P230 GM110702]
FX Dr. Bisagno has been authorized to study drug abuse substances in animal
models by A.N.M.A.T. (National Board of Medicine Food and Medical
Technology, Ministerio de Salud, Argentina). Dr. Betina Gonzalez is a
recipient of a Postdoctoral Award from Fundacion Bunge y Born. This work
is supported by Grants PIP 11420100100072, PICT 2012-0924, PICT
2012-1769, Argentina, and by NIH awards P20 GM103425 and P230 GM110702
to the Center for Translational Neuroscience.
NR 54
TC 1
Z9 1
U1 3
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
EI 1476-3524
J9 NEUROTOX RES
JI Neurotox. Res.
PD JAN
PY 2015
VL 27
IS 1
BP 71
EP 83
DI 10.1007/s12640-014-9493-9
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AY4NO
UT WOS:000347555800007
PM 25261212
ER
PT J
AU Bouchard, C
Antunes-Correa, LM
Ashley, EA
Franklin, N
Hwang, PM
Mattsson, CM
Negrao, CE
Phillips, SA
Sarzynski, MA
Wang, PY
Wheeler, MT
AF Bouchard, Claude
Antunes-Correa, Ligia M.
Ashley, Euan A.
Franklin, Nina
Hwang, Paul M.
Mattsson, C. Mikael
Negrao, Carlos E.
Phillips, Shane A.
Sarzynski, Mark A.
Wang, Ping-yuan
Wheeler, Matthew T.
TI Personalized Preventive Medicine: Genetics and the Response to Regular
Exercise in Preventive Interventionse
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Personalized medicine; Individual differences; Genetics; Mitochondria;
Endothelium
ID CHRONIC HEART-FAILURE; ALL-CAUSE MORTALITY; RANDOMIZED CONTROLLED-TRIAL;
CORONARY-ARTERY-DISEASE; FLOW-MEDIATED DILATION; MAXIMAL AEROBIC POWER;
WIDE LINKAGE SCAN; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; HERITAGE FAMILY
AB Regular exercise and a physically active lifestyle have favorable effects on health. Several issues related to this theme are addressed in this report. A comment on the requirements of personalized exercise medicine and in-depth biological profiling along with the opportunities that they offer is presented. This is followed by a brief overview of the evidence for the contributions of genetic differences to the ability to benefit from regular exercise. Subsequently, studies showing that mutations in TP53 influence exercise capacity in mice and humans are succinctly described. The evidence for effects of exercise on endothelial function in health and disease also is covered. Finally, changes in cardiac and skeletal muscle in response to exercise and their implications for patients with cardiac disease are summarized. Innovative research strategies are needed to define the molecular mechanisms involved in adaptation to exercise and to translate them into useful clinical and public health applications. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Bouchard, Claude; Sarzynski, Mark A.] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70806 USA.
[Antunes-Correa, Ligia M.; Negrao, Carlos E.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil.
[Ashley, Euan A.; Mattsson, C. Mikael; Wheeler, Matthew T.] Stanford Univ, Div Cardiovasc Med, Ctr Inherited Cardiovasc Dis, Stanford, CA 94305 USA.
[Ashley, Euan A.; Wheeler, Matthew T.] Stanford Univ, Sch Med, Cardiovasc Inst, Stanford, CA 94305 USA.
[Franklin, Nina; Phillips, Shane A.] Univ Illinois, Dept Med, Integrat Physiol Lab, Dept Phys Therapy, Chicago, IL USA.
[Hwang, Paul M.; Wang, Ping-yuan] NHLBI, NIH, Bethesda, MD 20892 USA.
[Mattsson, C. Mikael] Swedish Sch Sport & Hlth Sci, Stockholm, Sweden.
[Negrao, Carlos E.] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil.
RP Bouchard, C (reprint author), Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70806 USA.
EM claude.bouchard@pbrc.edu
RI OCRC, FAPESP/K-1312-2015; Sarzynski, Mark/A-9798-2014; Bouchard,
Claude/A-7637-2009; Negrao, Carlos /C-4281-2012
OI OCRC, FAPESP/0000-0003-4596-1043;
FU National Institutes of Health [HL-45670]; Division of Intramural
Research, National Heart, Lung, and Blood Institutes (NHLBI);
Bench-to-Bedside of the National Institutes of Health; Fundacao de
Amparo a Pesquisa do Estado de Sao Paulo FAPESP [2013/15651-7,
2013/07607-8]; CNPq [301867/2010-0]; FAPESP [2013/07607-8,
2010/50048-1]; Fundacao Zerbini
FX C Bouchard is partially supported by the John W. Barton, Sr. Chair in
Genetics and Nutrition. Research on the HERITAGE Family Study was
supported for over 20 years by the National Institutes of Health
(HL-45670). PY Wang and PM Hwang are supported by the Division of
Intramural Research, National Heart, Lung, and Blood Institutes (NHLBI)
and by a Bench-to-Bedside of the National Institutes of Health. LM
Antunes-Correa was supported by Fundacao de Amparo a Pesquisa do Estado
de Sao Paulo FAPESP (2013/15651-7 and 2013/07607-8). CE Negrao was
supported by CNPq (301867/2010-0), FAPESP (2010/50048-1 and
2013/07607-8), and, in part, by Fundacao Zerbini.
NR 92
TC 8
Z9 8
U1 3
U2 18
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD JAN-FEB
PY 2015
VL 57
IS 4
BP 337
EP 346
DI 10.1016/j.pcad.2014.08.005
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AZ1MU
UT WOS:000348003900008
PM 25559061
ER
PT J
AU Zhang, X
Belkina, N
Jacob, HKC
Maity, T
Biswas, R
Venugopalan, A
Shaw, PG
Kim, MS
Chaerkady, R
Pandey, A
Guha, U
AF Zhang, Xu
Belkina, Natalya
Jacob, Harrys Kishore Charles
Maity, Tapan
Biswas, Romi
Venugopalan, Abhilash
Shaw, Patrick G.
Kim, Min-Sik
Chaerkady, Raghothama
Pandey, Akhilesh
Guha, Udayan
TI Identifying novel targets of oncogenic EGF receptor signaling in lung
cancer through global phosphoproteomics
SO PROTEOMICS
LA English
DT Article
DE Autophagy; EGFR; Erlotinib; Mass spectrometry; NSCLC; Phosphoproteomics;
SILAC
ID HIGHLY SELECTIVE ENRICHMENT; PROTEIN PHOSPHATASE 2A; TITANIUM-DIOXIDE;
POSTTRANSLATIONAL MODIFICATIONS; PHOSPHORYLATED PEPTIDES; CELL-CULTURE;
AMINO-ACIDS; GEFITINIB; KINASE; RESISTANCE
AB Mutations in the epidermal growth factor receptor (EGFR) kinase domain occur in 10-30% of lung adenocarcinoma and are associated with tyrosine kinase inhibitor (TKI) sensitivity. We sought to identify the immediate direct and indirect phosphorylation targets of mutant EGFRs in lung adenocarcinoma. We undertook SILAC strategy, phosphopeptide enrichment, and quantitative MS to identify dynamic changes of phosphorylation downstream of mutant EGFRs in lung adenocarcinoma cells harboring EGFR(L858R) and EGFR(L858R/T790M), the TKI-sensitive, and TKI-resistant mutations, respectively. Top canonical pathways that were inhibited upon erlotinib treatment in sensitive cells, but not in the resistant cells include EGFR, insulin receptor, hepatocyte growth factor, mitogen-activated protein kinase, mechanistic target of rapamycin, ribosomal protein S6 kinase beta 1, and Janus kinase/signal transducer and activator of transcription signaling. We identified phosphosites in proteins of the autophagy network, such as ULK1 (S623) that is constitutively phosphorylated in these lung adenocarcinoma cells; phosphorylation is inhibited upon erlotinib treatment in sensitive cells, but not in resistant cells. Finally, kinase-substrate prediction analysis from our data indicated that substrates of basophilic kinases from, AGC and Calcium and calmodulin-dependent kinase groups, as well as STE group kinases were significantly enriched and those of proline-directed kinases from, CMGC and Casein kinase groups were significantly depleted among substrates that exhibited increased phosphorylation upon EGF stimulation and reduced phosphorylation upon TKI inhibition. This is the first study to date to examine global phosphorylation changes upon erlotinib treatment of lung adenocarcinoma cells and results from this study provide new insights into signaling downstream of mutant EGFRs in lung adenocarcinoma. All MS data have been deposited in the ProteomeXchange with identifier PXD001101 (http://proteomecentral.proteomexchange.org/dataset/PXD001101).
C1 [Zhang, Xu; Belkina, Natalya; Maity, Tapan; Biswas, Romi; Venugopalan, Abhilash; Guha, Udayan] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Jacob, Harrys Kishore Charles] Inst Bioinformat, Bangalore, Karnataka, India.
[Jacob, Harrys Kishore Charles; Shaw, Patrick G.; Kim, Min-Sik; Chaerkady, Raghothama; Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Jacob, Harrys Kishore Charles] Manipal Univ, Manipal, Karnataka, India.
[Pandey, Akhilesh] Johns Hopkins Univ, Dept Pathol, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Pandey, Akhilesh] Johns Hopkins Univ, Dept Oncol, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
RP Guha, U (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM udayan.guha@nih.gov
FU U.S. National Cancer Institute Center for Cancer Research (NCI-CCR) [ZIA
BC 011410]; K99 Career Transition award [K99CA140792]; NIH
[U54GM103520]; NCI's Clinical Proteomic Tumor Analysis Consortium
initiative [U24CA160036]; National Heart, Lung and Blood Institute
[HHSN268201000032C]; Council of Scientific and Industrial Research
(CSIR), India
FX This work was supported by U.S. National Cancer Institute Center for
Cancer Research (NCI-CCR) Intramural Research Program ZIA BC 011410
(U.G.) and K99 Career Transition award (K99CA140792) (U.G.). The work
was also supported in part by an NIH roadmap grant for Technology
Centers of Networks and Pathways (U54GM103520), NCI's Clinical Proteomic
Tumor Analysis Consortium initiative (U24CA160036), and a contract
(HHSN268201000032C) from the National Heart, Lung and Blood Institute
(A.P.). H.K.C.J. was a recipient of a Senior Research Fellowship from
Council of Scientific and Industrial Research (CSIR), India.
NR 58
TC 11
Z9 11
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
EI 1615-9861
J9 PROTEOMICS
JI Proteomics
PD JAN
PY 2015
VL 15
IS 2-3
SI SI
BP 340
EP 355
DI 10.1002/pmic.201400315
PG 16
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AY9UI
UT WOS:000347895500017
PM 25404012
ER
PT J
AU Kim, Y
van Ryn, M
Jensen, RE
Griffin, JM
Potosky, A
Rowland, J
AF Kim, Youngmee
van Ryn, Michelle
Jensen, Roxanne E.
Griffin, Joan M.
Potosky, Arnold
Rowland, Julia
TI Effects of gender and depressive symptoms on quality of life among
colorectal and lung cancer patients and their family caregivers
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE depressive symptoms; quality of life; dyadic adjustment; gender; cancer;
oncology
ID PSYCHOLOGICAL DISTRESS; SPOUSE CAREGIVERS; PSYCHOSOCIAL CARE;
BREAST-CANCER; HEALTH; COMORBIDITY; TRAJECTORIES; METAANALYSIS;
SURVIVORS; OUTCOMES
AB ObjectiveCancer patients and their family caregivers often report elevated levels of depressive symptoms, along with poorer mental and physical health (quality of life: QOL). Although the mutuality in distress between patients and their caregivers is relatively well known, unknown are the degree to which caregivers' depressive symptoms independently predict their patient's QOL and vice versa, and whether the relations vary by cancer type or gender.
MethodsColorectal or lung cancer patients and their caregivers (398 dyads) provided complete data for study variables (212 colorectal cancer patient dyads, 186 lung cancer patient dyads; 257 male patient dyads, 141 female patient dyads). Patients' depressive symptoms and QOL were measured approximately 4 and 12months post-diagnosis; caregivers' depressive symptoms and QOL were measured approximately 5months post-diagnosis.
ResultsThe actor-partner interdependence model confirmed that each person's depressive symptom level was uniquely associated with his/her own concurrent QOL. Female patients' depressive symptoms were also related to their caregivers' poorer physical and better mental health, particularly when the pair's depressive symptoms were at similarly elevated level. On the other hand, male patients' elevated depressive symptoms were related to their caregivers' poorer mental health.
ConclusionsFindings suggest that QOL among patients and their family caregivers is interdependent. In light of this interdependency, psychosocial interventions for managing depressive symptoms should target both patients and their family caregivers, from which both may benefit by not only alleviating depressive symptoms but also improving QOL. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Kim, Youngmee] Univ Miami, Coral Gables, FL 33124 USA.
[van Ryn, Michelle] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Jensen, Roxanne E.; Potosky, Arnold] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Griffin, Joan M.] Minneapolis VA Med Ctr, Minneapolis, MN USA.
[Rowland, Julia] NCI, Bethesda, MD 20892 USA.
RP Kim, Y (reprint author), Univ Miami, Dept Psychol, 5665 Ponce de Leon Blvd, Coral Gables, FL 33124 USA.
EM ykim@miami.edu
OI Kim, Youngmee/0000-0002-3109-6362
FU National Cancer Institute [U01 CA93324, U01 CA93326, U01 CA93329, U01
CA93332, U01 CA93339, U01 CA93344, U01 CA93348]; Department of Veterans
Affairs [CRS 02-164]; Sylvester Comprehensive Cancer Center, University
of Miami, FL
FX This study was supported by grants from the National Cancer Institute
(U01 CA93324, U01 CA93326, U01 CA93329, U01 CA93332, U01 CA93339, U01
CA93344, and U01 CA93348) and the Department of Veterans Affairs (CRS
02-164). Writing of this manuscript was supported by the Sylvester
Comprehensive Cancer Center, University of Miami, FL, to the first
author. The first author dedicates this research to the memory of
Heekyoung Kim.
NR 39
TC 10
Z9 10
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD JAN
PY 2015
VL 24
IS 1
BP 95
EP 105
DI 10.1002/pon.3580
PG 11
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA AY9TY
UT WOS:000347894500013
PM 24831223
ER
PT J
AU Fleming, SM
Maniscalco, B
Ko, Y
Amendi, N
Ro, T
Lau, H
AF Fleming, Stephen M.
Maniscalco, Brian
Ko, Yoshiaki
Amendi, Namema
Ro, Tony
Lau, Hakwan
TI Action-Specific Disruption of Perceptual Confidence
SO PSYCHOLOGICAL SCIENCE
LA English
DT Article
DE perception; motor processes; monitoring; open data
ID TRANSCRANIAL MAGNETIC STIMULATION; DORSAL PREMOTOR CORTEX; FRONTAL EYE
FIELDS; DECISION-MAKING; SIGNAL-DETECTION; PARIETAL CORTEX; NEURAL
BASIS; SELECTION; MOVEMENT; METACOGNITION
AB Theoretical models of perception assume that confidence is related to the quality or strength of sensory processing. Counter to this intuitive view, we showed in the present research that the motor system also contributes to judgments of perceptual confidence. In two experiments, we used transcranial magnetic stimulation (TMS) to manipulate response-specific representations in the premotor cortex, selectively disrupting postresponse confidence in visual discrimination judgments. Specifically, stimulation of the motor representation associated with the unchosen response reduced confidence in correct responses, thereby reducing metacognitive capacity without changing visual discrimination performance. Effects of TMS on confidence were observed when stimulation was applied both before and after the response occurred, which suggests that confidence depends on late-stage metacognitive processes. These results place constraints on models of perceptual confidence and metacognition by revealing that action-specific information in the premotor cortex contributes to perceptual confidence.
C1 [Fleming, Stephen M.] NYU, Ctr Neural Sci, New York, NY 10003 USA.
[Fleming, Stephen M.] Univ Oxford, Dept Expt Psychol, Oxford OX1 2JD, England.
[Maniscalco, Brian; Ko, Yoshiaki; Amendi, Namema; Lau, Hakwan] Columbia Univ, Dept Psychol, New York, NY 10027 USA.
[Maniscalco, Brian] NINDS, NIH, Bethesda, MD 20892 USA.
[Ro, Tony] CUNY City Coll, Dept Psychol, New York, NY 10031 USA.
[Lau, Hakwan] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
RP Fleming, SM (reprint author), NYU, Ctr Neural Sci, 6 Washington Pl, New York, NY 10003 USA.
EM sf102@nyu.edu
RI Trivedi, Kruti/E-7558-2015
FU NINDS NIH HHS [R01 NS088628, R01NS088628]; Wellcome Trust [091593,
WT096185]
NR 41
TC 19
Z9 19
U1 3
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0956-7976
EI 1467-9280
J9 PSYCHOL SCI
JI Psychol. Sci.
PD JAN
PY 2015
VL 26
IS 1
BP 89
EP 98
DI 10.1177/0956797614557697
PG 10
WC Psychology, Multidisciplinary
SC Psychology
GA AZ0RW
UT WOS:000347953200009
PM 25425059
ER
PT J
AU Peprah, E
Xu, HC
Tekola-Ayele, F
Royal, CD
AF Peprah, Emmanuel
Xu, Huichun
Tekola-Ayele, Fasil
Royal, Charmaine D.
TI Genome-Wide Association Studies in Africans and African Americans:
Expanding the Framework of the Genomics of Human Traits and Disease
SO PUBLIC HEALTH GENOMICS
LA English
DT Review
DE African American; African ancestry; African populations; Genetic
conditions; Genome-wide association studies; Genomics; Global health;
Health
ID FRAGILE-X-SYNDROME; SICKLE-CELL-DISEASE; PROSTATE-CANCER; WHOLE-GENOME;
COMMUNITY ENGAGEMENT; ALCOHOL DEPENDENCE; EUROPEAN-AMERICAN; GENETIC
DIVERSITY; COMPLEX DISEASE; VARIANTS
AB Genomic research is one of the tools for elucidating the pathogenesis of diseases of global health relevance and paving the research dimension to clinical and public health translation. Recent advances in genomic research and technologies have increased our understanding of human diseases, genes associated with these disorders, and the relevant mechanisms. Genome-wide association studies (GWAS) have proliferated since the first studies were published several years ago and have become an important tool in helping researchers comprehend human variation and the role genetic variants play in disease. However, the need to expand the diversity of populations in GWAS has become increasingly apparent as new knowledge is gained about genetic variation. Inclusion of diverse populations in genomic studies is critical to a more complete understanding of human variation and elucidation of the underpinnings of complex diseases. In this review, we summarize the available data on GWAS in recent African ancestry populations within the western hemisphere (i.e. African Americans and peoples of the Caribbean) and continental African populations. Furthermore, we highlight ways in which genomic studies in populations of recent African ancestry have led to advances in the areas of malaria, HIV, prostate cancer, and other diseases. Finally, we discuss the advantages of conducting GWAS in recent African ancestry populations in the context of addressing existing and emerging global health conditions. (C) 2014 S. Karger AG, Basel
C1 [Peprah, Emmanuel] NHLBI, Ctr Translat Res & Implementat Sci, Bethesda, MD 20817 USA.
[Tekola-Ayele, Fasil] NIH, Ctr Res Genom & Global Hlth, Natl Human Genome Res Inst, Bethesda, MD 20892 USA.
[Xu, Huichun] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Royal, Charmaine D.] Duke Univ, Dept African & African Amer Studies, Durham, NC USA.
RP Peprah, E (reprint author), NHLBI, Ctr Translat Res & Implementat Sci, NIH, 6705 Rockledge Dr,Suite 6070, Bethesda, MD 20817 USA.
EM peprahek@mail.nih.gov
OI Tekola-Ayele, Fasil/0000-0003-4194-9370
FU NIA [T32-AG000219]
FX The authors kindly acknowledge and also thank Dr. Daniel Shriner at the
Center for Research on Genomics and Global Health (CRGGH), and the NIH
Fellows Editorial Board for editorial advice and careful reading of the
manuscript. This research was supported in part by an NIA training grant
to the University of Maryland (T32-AG000219).
NR 112
TC 6
Z9 6
U1 0
U2 10
PU KARGER
PI BASEL
PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND
SN 1662-4246
EI 1662-8063
J9 PUBLIC HEALTH GENOM
JI Pub. Health Genomics
PY 2015
VL 18
IS 1
BP 40
EP 51
DI 10.1159/000367962
PG 12
WC Genetics & Heredity; Public, Environmental & Occupational Health
SC Genetics & Heredity; Public, Environmental & Occupational Health
GA AY6YH
UT WOS:000347708100005
PM 25427668
ER
PT J
AU Wendler, DS
Rid, A
AF Wendler, David S.
Rid, Annette
TI Genetic research on biospecimens poses minimal risk
SO TRENDS IN GENETICS
LA English
DT Review
DE minimal risk; genetic research; confidentiality
ID GENOMICS; IDENTIFIABILITY; FRAMEWORK; ATTITUDES; STANDARD; SAMPLES
AB Genetic research on human biospecimens is increasingly common. However, debate continues over the level of risk that this research poses to sample donors. Some argue that genetic research on biospecimens poses minimal risk; others argue that it poses greater than minimal risk and therefore needs additional requirements and limitations. This debate raises concern that some donors are not receiving appropriate protection or, conversely, that valuable research is being subject to unnecessary requirements and limitations. The present paper attempts to resolve this debate using the widely-endorsed 'risks of daily life' standard. The three extant versions of this standard all suggest that, with proper measures in place to protect confidentiality, most genetic research on human biospecimens poses minimal risk to donors.
C1 [Wendler, David S.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Rid, Annette] Kings Coll London, Dept Social Sci Hlth & Med, London, England.
RP Wendler, DS (reprint author), NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
FU Intramural Research Program, NIH Clinical Center; University of Zurich
(Nachwuchsforderungskredit); European Commission
[FP7-PEOPLE-2011-IEF-301816]
FX Thanks to Ben Berkman JD, NIH, Christine Grady PhD, NIH, Sara Hull PhD,
NIH and Barbara Prainsack PhD, King's College London for their helpful
comments on previous drafts of the manuscript. This work was supported
by the Intramural Research Program, NIH Clinical Center. However, the
opinions expressed are the authors' own. They do not represent the
position or policy of the NIH. Annette Rid received funding from the
University of Zurich (Nachwuchsforderungskredit) and the European
Commission (FP7-PEOPLE-2011-IEF-301816).
NR 34
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0168-9525
J9 TRENDS GENET
JI Trends Genet.
PD JAN
PY 2015
VL 31
IS 1
BP 11
EP 15
DI 10.1016/j.tig.2014.10.003
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA AY9JW
UT WOS:000347867200004
PM 25530152
ER
PT J
AU Lopez, MA
Basco, MA
AF Lopez, Molly A.
Basco, Monica A.
TI Effectiveness of Cognitive Behavioral Therapy in Public Mental Health:
Comparison to Treatment as Usual for Treatment-Resistant Depression
SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES
RESEARCH
LA English
DT Article
DE Cognitive behavioral therapy; Depression; Evidence-based practices;
Effectiveness
ID RANDOMIZED CLINICAL-TRIAL; PSYCHOLOGISTS ATTITUDES; TREATING DEPRESSION;
COST-EFFECTIVENESS; FLUOXETINE PROZAC; EXPOSURE THERAPY; MAJOR
DEPRESSION; NATIONAL-SURVEY; PSYCHOTHERAPY; DISSEMINATION
AB State mental health systems have been leaders in the implementation of evidence-based approaches to care for individuals with severe mental illness. Numerous case studies of the wide-scale implementation of research-supported models such as integrated dual diagnosis treatment and assertive community treatment are documented. However, relatively few dissemination efforts have focused on cognitive behavioral therapy (CBT) for individuals with major depression despite evidence indicating its efficacy with this population. A multi-site effectiveness trial of CBT was conducted within the Texas public mental health system. Eighty-three adults with major depression received CBT from community clinicians trained through a workshop and regular consultation with a master clinician. Outcomes were compared to a matched sample of individuals receiving pharmacotherapy. Outcome measures used included the quick inventory of depressive symptomatology and beck depression inventory. Individuals receiving CBT showed greater improvements in depression symptoms than those in the comparison group. Greater pre-treatment symptom severity predicted better treatment response, while the presence of comorbid personality disorders was associated with poorer outcomes.
C1 [Lopez, Molly A.] Univ Texas Austin, Sch Social Work, Austin, TX 78703 USA.
[Basco, Monica A.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
RP Lopez, MA (reprint author), Univ Texas Austin, Sch Social Work, 1717 West 6th St,Suite 335, Austin, TX 78703 USA.
EM mlopez@mail.utexas.edu
FU NIMH NIH HHS [R34 MH074749, R34MH074749]
NR 57
TC 4
Z9 4
U1 4
U2 35
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0894-587X
EI 1573-3289
J9 ADM POLICY MENT HLTH
JI Adm. Policy. Ment. Health
PD JAN
PY 2015
VL 42
IS 1
BP 87
EP 98
DI 10.1007/s10488-014-0546-4
PG 12
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AY2EK
UT WOS:000347401200010
PM 24692026
ER
PT J
AU Aoun, EG
Lee, MR
Haass-Koffler, CL
Swift, RM
Addolorato, G
Kenna, GA
Leggio, L
AF Aoun, Elie G.
Lee, Mary R.
Haass-Koffler, Carolina L.
Swift, Robert M.
Addolorato, Giovanni
Kenna, George A.
Leggio, Lorenzo
TI Relationship Between the Thyroid Axis and Alcohol Craving
SO ALCOHOL AND ALCOHOLISM
LA English
DT Article
ID THYROTROPIN-RELEASING-HORMONE; COMPULSIVE DRINKING SCALE; DEPENDENT
PATIENTS; RAT-BRAIN; ETHANOL; BACLOFEN; SYSTEM; STIMULATION; AGGRESSION;
VALIDATION
AB Aims: A few studies have suggested a relationship between thyroid hormones and alcohol dependence (AD) such as a blunted increase of thyroid stimulating hormone (TSH) in response to thyrotropin-releasing hormone (TRH), lower levels of circulating free triiodothyronine (fT3) and free thyroxine (fT4) levels and down regulation of the TRH receptors. The current study aimed to explore the relationship between the hormones of the thyroid axis and alcohol-seeking behaviors in a sample of alcohol-dependent patients. Methods: Forty-two treatment-seeking alcohol-dependent individuals enrolled in a 12-week treatment study were considered. The Timeline Follow Back (TLFB) was used to assess the number of drinks consumed during the 12-week period. Blood levels of thyroid hormones (TSH, fT3 and fT4) were measured prior to and at the end of treatment. Questionnaires were administered to evaluate craving for alcohol [Penn Alcohol Craving Scale (PACS) and the Obsessive Compulsive Drinking Scale (OCDS) and its two subscales ODS for obsessions and CDS for compulsions] as well as anxiety [State and Trait Inventory (STAI)], depression [the Zung Self-Rating Depression Scale (Zung)] and aggression [the Aggressive Questionnaire (AQ)]. Results: At baseline, we found significant positive correlations between fT3 and OCDS (r = 0.358, P = 0.029) and CDS (r = 0.405, P = 0.013) and negative correlations between TSH levels and STAI (r = -0.342, P = 0.031), and AQ (r = -0.35, P = 0.027). At the end of the 12-week study period, abstinent patients had a greater change in TSH than those who relapsed (-0.4 vs. -0.25, F(1,24) = 5.4, P = 0.029). Conclusion: If confirmed in larger samples, these findings could suggest that the thyroid axis might represent a biomarker of alcohol craving and drinking.
C1 [Aoun, Elie G.; Lee, Mary R.; Haass-Koffler, Carolina L.; Swift, Robert M.; Addolorato, Giovanni; Kenna, George A.; Leggio, Lorenzo] Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Baltimore, MD 21224 USA.
RP Leggio, L (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Baltimore, MD 21224 USA.
EM lorenzo.leggio@nih.gov
RI Leggio, Lorenzo/M-2972-2016
FU European Foundation for Alcohol Research (ERAB); Division of Intramural
Clinical and Biological Research of the National Institute on Alcohol
Abuse and Alcoholism (NIAAA); Intramural Research Program of the
National Institute on Drug Abuse (NIDA); Brown University - National
Institute of Mental Health (NIMH) [R25MH101076]; Brown University -
NIAAA [5T32AA007459-28]; NIAAA [R21AA021128]
FX Support for this study was partially provided by an Exchange Award from
the European Foundation for Alcohol Research (ERAB) to L.L. when he was
working at Brown University, Providence, RI. At present, L.L. and M.R.L.
are federal employees in the Section on Clinical
Psychoneuroendocrinology and Neuropsychopharmacology, which is supported
by the Division of Intramural Clinical and Biological Research of the
National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the
Intramural Research Program of the National Institute on Drug Abuse
(NIDA). E.G.A.'s work is supported by a Brown University research
education grant funded by the National Institute of Mental Health (NIMH;
R25MH101076). C.L.H.-K.'s work is supported by a Brown University
training grant funded by NIAAA (5T32AA007459-28). G.A.K.'s work is
supported by R21AA021128 from NIAAA.
NR 36
TC 1
Z9 1
U1 2
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD JAN-FEB
PY 2015
VL 50
IS 1
BP 24
EP 29
DI 10.1093/alcalc/agu085
PG 6
WC Substance Abuse
SC Substance Abuse
GA AY2JL
UT WOS:000347415400004
PM 25433251
ER
PT J
AU Mannisto, T
Mendola, P
Liu, DP
Leishear, K
Sherman, S
Laughon, SK
AF Maennistoe, Tuija
Mendola, Pauline
Liu, Danping
Leishear, Kira
Sherman, Seth
Laughon, S. Katherine
TI Acute Air Pollution Exposure and Blood Pressure at Delivery Among Women
With and Without Hypertension
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE air pollution; blood pressure; epidemiology; hypertension; pregnancy
ID PARTICULATE MATTER; PREGNANT-WOMEN; PULSE PRESSURE; DISEASE; COHORT;
ADULTS; NONSMOKING; MORTALITY; RISK
AB BACKGROUND
Chronic air pollution exposure increases risk for hypertensive disorders of pregnancy, but the effect of acute air pollution exposure on blood pressure during pregnancy is less well known.
METHODS
We studied 151,276 singleton term deliveries from the Consortium on Safe Labor (2002-2008) with clinical blood pressure measured at admission to labor/delivery and diagnoses of hypertensive disorders collected from electronic medical records and hospital discharge summaries. Air pollution exposures were estimated for the admission hour and the 4 hours preceding admission using a modified version of the Community Multiscale Air Quality models and observed air monitoring data. Blood pressure was categorized as normal; high normal; and mild, moderate, or severe hypertension based on pregnancy cut points. Adjusted ordinal logistic regression estimated the odds of women having a higher admission blood pressure category as a function of air pollutant, hypertensive disorders, and their interaction effect.
RESULTS
Odds of high blood pressure at admission to labor/delivery were increased in normotensive women after exposure to nitrogen oxides (by 0.2%/5 units), sulfur dioxide (by 0.3%/1 unit), carbon monoxide and several air toxics (by 3%-4%/high exposure). The effects were often similar or stronger among women with gestational hypertension and preeclampsia. Exposure to particulate matter < 10 mu m increased odds of high blood pressure in women with preeclampsia by 3%/5 units.
CONCLUSIONS
Air pollution can influence admission blood pressure in term deliveries and may increase likelihood of preeclampsia screening at delivery admission.
C1 [Maennistoe, Tuija; Mendola, Pauline; Laughon, S. Katherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Leishear, Kira] Glotech, Rockville, MD USA.
[Sherman, Seth] EMMES Corp, Rockville, MD USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mannisto, Tuija/0000-0002-6382-9153; Mendola,
Pauline/0000-0001-5330-2844; Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603425C, HHSN275200800002I, HHSN27500008]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; including Contract No.
HHSN267200603425C (Consortium on Safe Labor) and Contract No.
HHSN275200800002I; Task Order No. HHSN27500008 (Air Quality and
Reproductive Health). Institutions involved in the consortium include:
Baystate Medical Center, Springfield, MA; Cedars-Sinai Medical Center
Burnes Allen Research Center, Los Angeles, CA; Christiana Care Health
System, Newark, DE; Georgetown University Hospital, MedStar Health,
Washington, DC; Indiana University Clarian Health, Indianapolis, IN;
Intermountain Healthcare and the University of Utah, Salt Lake City,
Utah; Maimonides Medical Center, Brooklyn, NY; MetroHealth Medical
Center, Cleveland, OH; Summa Health System, Akron City Hospital, Akron,
OH; The EMMES Corporation, Rockville, MD (Data Coordinating Center);
University of Illinois at Chicago, Chicago, IL; University of Miami,
Miami, FL; and University of Texas Health Science Center at Houston,
Houston, Texas. The Texas A&M Supercomputing Facility
(http://sc.tamu.edu) and the Texas Advanced Computing Center
(http://www.tacc.utexas.edu/) provided computing resources essential for
completing the air quality simulations for exposure estimations in this
study.
NR 32
TC 8
Z9 8
U1 0
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD JAN
PY 2015
VL 28
IS 1
BP 58
EP 72
DI 10.1093/ajh/hpu077
PG 15
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AY2JI
UT WOS:000347415100009
PM 24795401
ER
PT J
AU Cheresh, P
Morales-Nebreda, L
Kim, SJ
Yeldandi, A
Williams, DB
Cheng, Y
Mutlu, GM
Budinger, GRS
Ridge, K
Schumacker, PT
Bohr, VA
Kamp, DW
AF Cheresh, Paul
Morales-Nebreda, Luisa
Kim, Seok-Jo
Yeldandi, Anjana
Williams, David B.
Cheng, Yuan
Mutlu, Goekhan M.
Budinger, G. R. Scott
Ridge, Karen
Schumacker, Paul T.
Bohr, Vilhelm A.
Kamp, David W.
TI Asbestos-Induced Pulmonary Fibrosis Is Augmented in 8-Oxoguanine DNA
Glycosylase Knockout Mice
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE asbestosis; pulmonary fibrosis; mitochondria; 8-oxyguanosine DNA
glycosylase
ID ENDOPLASMIC-RETICULUM STRESS; EPITHELIAL-CELL APOPTOSIS;
MITOCHONDRIA-REGULATED APOPTOSIS; OXIDATIVE STRESS; REPAIR ENZYME;
GENE-EXPRESSION; LUNG CARCINOMAS; 1 PROTECTS; OGG1 GENE; DAMAGE
AB Asbestos causes asbestosis and malignancies by mechanisms that are not fully established. Alveolar epithelial cell (AEC) injury and repair are crucial determinants of the fibrogenic potential of noxious agents such as asbestos. We previously showed that mitochondrial reactive oxygen species mediate asbestos-induced AEC intrinsic apoptosis and that mitochondrial human 8-oxoguanine-DNA glycosylase 1 (OGG1), a DNA repair enzyme, prevents oxidant-induced AEC apoptosis. We reasoned that OGG1 deficiency augments asbestos-induced pulmonary fibrosis. Compared with intratracheal instillation of PBS (50 mu l) or titanium dioxide (100 mu g/50 mu l), crocidolite or Libby amphibole asbestos (100 mu g/50 mu l) each augmented pulmonary fibrosis in wild-type C57BL/6J (WT) mice after 3 weeks as assessed by histology, fibrosis score, lung collagen via Sircol, and type 1 collagen expression; these effects persisted at 2 months. Compared with WT mice, Ogg1 homozygous knockout (Ogg1(-/-)) mice exhibit increased pulmonary fibrosis after crocidolite exposure and apoptosis in cells at the bronchoalveolar duct junctions as assessed via cleaved caspase-3 immunostaining. AEC involvement was verified by colocalization studies using surfactant protein C. Asbestos increased endoplasmic reticulum stress in the lungs of WT and Ogg1(-/-) mice. Compared with WT, alveolar type 2 cells isolated from Ogg1(-/-) mice have increased mtDNA damage, reduced mitochondrial aconitase expression, and increased P53 and cleaved caspase-9 expression, and these changes were enhanced 3 weeks after crocidolite exposure. These findings suggest an important role for AEC mtDNA integrity maintained by OGG1 in the pathogenesis of pulmonary fibrosis that may represent a novel therapeutic target.
C1 [Cheresh, Paul; Morales-Nebreda, Luisa; Kim, Seok-Jo; Williams, David B.; Cheng, Yuan; Mutlu, Goekhan M.; Budinger, G. R. Scott; Ridge, Karen; Kamp, David W.] Jesse Brown VA Med Ctr, Dept Med, Div Pulm & Crit Care Med, Chicago, IL USA.
[Cheresh, Paul; Morales-Nebreda, Luisa; Kim, Seok-Jo; Williams, David B.; Cheng, Yuan; Mutlu, Goekhan M.; Budinger, G. R. Scott; Ridge, Karen; Kamp, David W.] Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA.
[Yeldandi, Anjana] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.
[Schumacker, Paul T.] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA.
RP Kamp, DW (reprint author), Northwestern Univ, Feinberg Sch Med Pulm & Crit Care Med, Mc Gaw M-330,240 E Huron St, Chicago, IL 60611 USA.
EM d-kamp@northwestern.edu
FU National Institutes of Health grants [RO1ES020357, R01HL071643,
NCICA0605531]; VA Merit award
FX This work was supported by National Institutes of Health grants
RO1ES020357 (D. W. K.), R01HL071643 (K. R.), and NCICA0605531 and by a
VA Merit award (D. W. K.).
NR 66
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Z9 7
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JAN
PY 2015
VL 52
IS 1
BP 25
EP 36
DI 10.1165/rcmb.2014-0038OC
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA AY2KY
UT WOS:000347420300003
PM 24918270
ER
PT J
AU Malve, M
Gharib, AM
Yazdani, SK
Finet, G
Martinez, MA
Pettigrew, R
Ohayon, J
AF Malve, M.
Gharib, A. M.
Yazdani, S. K.
Finet, G.
Martinez, M. A.
Pettigrew, R.
Ohayon, J.
TI Tortuosity of Coronary Bifurcation as a Potential Local Risk Factor for
Atherosclerosis: CFD Steady State Study Based on In Vivo Dynamic CT
Measurements
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE CFD; Wall shear stress; Hemodynamics; Tortuosity; Coronary bifurcation;
Atherosclerosis
ID WALL SHEAR-STRESS; NEWTONIAN BLOOD-FLOW; INTRAVASCULAR ULTRASOUND;
CAROTID BIFURCATION; ARTERY-DISEASE; COMPUTED-TOMOGRAPHY; FOLLOW-UP;
PATTERNS; PLAQUE; HEMODYNAMICS
AB The purpose of the present study was to determine whether in vivo bifurcation geometric factors would permit prediction of the risk of atherosclerosis. It is worldwide accepted that low or oscillatory wall shear stress (WSS) is a robust hemodynamic factor in the development of atherosclerotic plaque and has a strong correlation with the local site of plaque deposition. However, it still remains unclear how coronary bifurcation geometries are correlated with such hemodynamic forces. Computational fluid dynamics simulations were performed on left main (LM) coronary bifurcation geometries derived from CT of eight patients without significant atherosclerosis. WSS amplitudes were accurately quantified at two high risk zones of atherosclerosis, namely at proximal left anterior descending artery (LAD) and at proximal left circumflex artery (LCx), and also at three high WSS concentration sites near the bifurcation. Statistical analysis was used to highlight relationships between WSS amplitudes calculated at these five zones of interest and various geometric factors. The tortuosity index of the LM-LAD segment appears to be an emergent geometric factor in determining the low WSS amplitude at proximal LAD. Strong correlations were found between the high WSS amplitudes calculated at the endothelial regions close to the flow divider. This study not only demonstrated that CT imaging studies of local risk factor for atherosclerosis could be clinically performed, but also showed that tortuosity of LM-LAD coronary branch could be used as a surrogate marker for the onset of atherosclerosis.
C1 [Malve, M.] Univ Publ Navarra, Dept Mech Engn Energet & Mat, Pamplona 31006, Spain.
[Malve, M.; Martinez, M. A.] Univ Zaragoza, Aragon Inst Engn Res, Zaragoza, Spain.
[Malve, M.; Martinez, M. A.] CIBER BBN, Madrid, Spain.
[Gharib, A. M.; Pettigrew, R.] NIDDK, Lab Integrat Cardiovasc Imaging Sci, NIH, Bethesda, MD 20892 USA.
[Yazdani, S. K.] Univ S Alabama, Dept Mech Engn, Mobile, AL 36688 USA.
[Finet, G.] Hosp Civils Lyon, Dept Hemodynam & Intervent Cardiol, Lyon, France.
[Finet, G.] Univ Lyon 1, INSERM, U886, F-69365 Lyon, France.
[Ohayon, J.] In3S, CNRS UMR 5525, UJF, Lab TIMC DyCTiM, Grenoble, France.
[Ohayon, J.] Univ Savoie, Engn Sch Polytech Annecy Chambery, Chambery, France.
RP Malve, M (reprint author), Univ Publ Navarra, Dept Mech Engn Energet & Mat, Campus Arrosadia, Pamplona 31006, Spain.
EM mauro.malve@unavarra.es; jacques.ohayon@imag.fr
RI Martinez, Miguel Angel/F-5903-2011; Malve, Mauro/A-5516-2013; Gharib,
Ahmed/O-2629-2016
OI Martinez, Miguel Angel/0000-0002-8375-0354; Malve,
Mauro/0000-0002-0116-2736; Gharib, Ahmed/0000-0002-2476-481X
FU Spanish Ministry of Science and Technology [DPI-2010-20746-C03-01];
Instituto de Salud Carlos III (ISCIII) through the CIBER-BBN initiative;
National Institutes of Health (NIH)
FX M. Malve and M.A. Martinez are supported by the Spanish Ministry of
Science and Technology through research project DPI-2010-20746-C03-01
and the Instituto de Salud Carlos III (ISCIII) through the CIBER-BBN
initiative. This research was supported in part by an appointment (J.
Ohayon) to the Senior Fellow Program at the National Institutes of
Health (NIH). This program is administered by Oak Ridge Institute for
Science and Education through an inter-agency agreement between the NIH
and the U.S. Department of Energy.
NR 50
TC 6
Z9 7
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
EI 1573-9686
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD JAN
PY 2015
VL 43
IS 1
BP 82
EP 93
DI 10.1007/s10439-014-1056-y
PG 12
WC Engineering, Biomedical
SC Engineering
GA AY6QC
UT WOS:000347689700008
PM 24986333
ER
PT J
AU Morris, JH
Wu, A
Yamashita, RA
Marchler-Bauer, A
Ferrin, TE
AF Morris, John H.
Wu, Allan
Yamashita, Roxanne A.
Marchler-Bauer, Aron
Ferrin, Thomas E.
TI cddApp: a Cytoscape app for accessing the NCBI conserved domain database
SO BIOINFORMATICS
LA English
DT Article
ID UCSF-CHIMERA; VISUALIZATION; NETWORKS
AB Motivation: cddApp is a Cytoscape extension that supports the annotation of protein networks with information about domains and specific functional sites from the National Center for Biotechnology Information's conserved domain database (CDD). CDD information is loaded for nodes annotated with NCBI numbers or UniProt identifiers and (optionally) Protein Data Bank structures. cddApp integrates with the Cytoscape apps structureViz2 and enhancedGraphics. Together, these three apps provide powerful tools to annotate nodes with CDD domain and site information and visualize that information in both network and structural contexts.
C1 [Morris, John H.; Wu, Allan; Ferrin, Thomas E.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yamashita, Roxanne A.; Marchler-Bauer, Aron] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Morris, JH (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
EM scooter@cgl.ucsf.edu
FU Intramural Research Program of the U.S. National Institutes of Health
(NIH); National Library of Medicine; NIH National Institute of General
Medical Science [P41-GM103311]
FX This research was supported in part by the Intramural Research Program
of the U.S. National Institutes of Health (NIH); National Library of
Medicine; and by NIH National Institute of General Medical Science Grant
[P41-GM103311].
NR 10
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JAN 1
PY 2015
VL 31
IS 1
BP 134
EP 136
DI 10.1093/bioinformatics/btu605
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA AY2JU
UT WOS:000347417000025
PM 25212755
ER
PT J
AU Samish, I
Bourne, PE
Najmanovich, RJ
AF Samish, Ilan
Bourne, Philip E.
Najmanovich, Rafael J.
TI Achievements and challenges in structural bioinformatics and
computational biophysics
SO BIOINFORMATICS
LA English
DT Article
ID PROTEIN-STRUCTURE PREDICTION; MOLECULAR RECOGNITION; DRUG DISCOVERY;
SIMULATION; DESIGN; 3D; PRINCIPLES; DOCKING; BIOLOGY; SIMILARITIES
AB Motivation: The field of structural bioinformatics and computational biophysics has undergone a revolution in the last 10 years. Developments that are captured annually through the 3DSIG meeting, upon which this article reflects.
Results: An increase in the accessible data, computational resources and methodology has resulted in an increase in the size and resolution of studied systems and the complexity of the questions amenable to research. Concomitantly, the parameterization and efficiency of the methods have markedly improved along with their cross-validation with other computational and experimental results.
Conclusion: The field exhibits an ever-increasing integration with biochemistry, biophysics and other disciplines. In this article, we discuss recent achievements along with current challenges within the field.
C1 [Samish, Ilan] Weizmann Inst Sci, Dept Plant Sci, IL-76100 Rehovot, Israel.
[Samish, Ilan] Ort Braude Coll, IL-2161002 Karmiel, Israel.
[Bourne, Philip E.] NIH, Bethesda, MD 20814 USA.
[Najmanovich, Rafael J.] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1H 5N4, Canada.
RP Najmanovich, RJ (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1H 5N4, Canada.
EM Rafael.Najmanovich@USherbrooke.ca
RI samish, ilan/B-7980-2016;
OI samish, ilan/0000-0002-0299-9124; Najmanovich,
Rafael/0000-0002-6971-7224
NR 77
TC 6
Z9 6
U1 3
U2 22
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JAN 1
PY 2015
VL 31
IS 1
BP 146
EP 150
DI 10.1093/bioinformatics/btu769
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA AY2JU
UT WOS:000347417000029
PM 25488929
ER
PT J
AU Elliott, KC
Resnik, DB
AF Elliott, Kevin C.
Resnik, David B.
TI Scientific Reproducibility, Human Error, and Public Policy
SO BIOSCIENCE
LA English
DT Editorial Material
C1 [Elliott, Kevin C.] Michigan State Univ, Lyman Briggs Coll, Dept Fisheries & Wildlife, E Lansing, MI 48824 USA.
[Elliott, Kevin C.] Michigan State Univ, Dept Philosophy, E Lansing, MI 48824 USA.
[Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Elliott, KC (reprint author), Michigan State Univ, Lyman Briggs Coll, Dept Fisheries & Wildlife, E Lansing, MI 48824 USA.
EM kce@msu.edu
NR 11
TC 3
Z9 3
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-3568
EI 1525-3244
J9 BIOSCIENCE
JI Bioscience
PD JAN
PY 2015
VL 65
IS 1
BP 5
EP 6
DI 10.1093/biosci/biu197
PG 2
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA AY2KF
UT WOS:000347418200002
ER
PT J
AU Yu, K
Zhang, H
Wheeler, W
Horne, HN
Chen, JB
Figueroa, JD
AF Yu, Kai
Zhang, Han
Wheeler, William
Horne, Hisani N.
Chen, Jinbo
Figueroa, Jonine D.
TI A robust association test for detecting genetic variants with
heterogeneous effects
SO BIOSTATISTICS
LA English
DT Article
DE Breast cancer; Etiology heterogeneity; Genetic association study;
Multiple-comparison adjustment; Tree-based model
ID BREAST-CANCER RISK; REGRESSION-MODEL; CONSORTIUM; LOCI
AB One common strategy for detecting disease-associated genetic markers is to compare the genotype distributions between cases and controls, where cases have been diagnosed as having the disease condition. In a study of a complex disease with a heterogeneous etiology, the sampled case group most likely consists of people having different disease subtypes. If we conduct an association test by treating all cases as a single group, we maximize our chance of finding genetic risk factors with a homogeneous effect, regardless of the underlying disease etiology. However, this strategy might diminish the power for detecting risk factors whose effect size varies by disease subtype. We propose a robust statistical procedure to identify genetic risk factors that have either a uniform effect for all disease subtypes or heterogeneous effects across different subtypes, in situations where the subtypes are not predefined but can be characterized roughly by a set of clinical and/or pathologic markers. We demonstrate the advantage of the new procedure through numeric simulation studies and an application to a breast cancer study.
C1 [Yu, Kai; Zhang, Han; Horne, Hisani N.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Wheeler, William] Informat Management Serv Inc, Rockville, MD 20892 USA.
[Chen, Jinbo] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
EM yuka@mail.nih.gov
RI Zhang, Han/K-2118-2016
OI Zhang, Han/0000-0001-7977-9616
FU Intramural Program of the NIH; National Cancer Institute;
[R01-ES016626]
FX The work of Kai Yu, Han Zhang, Hisani N. Horne, and Jinbo Chen was
supported in part by the Intramural Program of the NIH and the National
Cancer Institute. The work of Jinbo Chen was supported by R01-ES016626.
The authors of the study thank Pei Chao and Michael Stagner from
Information Management Services (Silver Spring, MD, USA) for data
management support; the participants, physicians, pathologists, nurses,
and interviewers from participating centers in Poland for their efforts
during field work; and Drs. Montse Garcia-Closas, Louise Brinton, Mark
Sherman, Beata Peplonska, and Jolanta Lissowska for their contributions
to the study design of the NCI Polish Breast Cancer Study.
NR 16
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U1 2
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2015
VL 16
IS 1
BP 5
EP 16
DI 10.1093/biostatistics/kxu036
PG 12
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA AY2JZ
UT WOS:000347417500003
PM 25057183
ER
PT J
AU Lum, KJ
Sundaram, R
Louis, TA
AF Lum, Kirsten J.
Sundaram, Rajeshwari
Louis, Thomas A.
TI Accounting for length-bias and selection effects in estimating the
distribution of menstrual cycle length
SO BIOSTATISTICS
LA English
DT Article
DE Backward recurrence time; Length-bias; Menstrual cycle length; Renewal
process; Selection effects; Survival analysis
ID NONPARAMETRIC-ESTIMATION; CONFIDENCE-INTERVALS; RENEWAL PROCESSES;
RANDOM TRUNCATION; ESTIMATING TIME; PREGNANCY; MODEL; PATTERNS; LIFE
AB Prospective pregnancy studies are a valuable source of longitudinal data on menstrual cycle length. However, care is needed when making inferences of such renewal processes. For example, accounting for the sampling plan is necessary for unbiased estimation of the menstrual cycle length distribution for the study population. If couples can enroll when they learn of the study as opposed to waiting for the start of a new menstrual cycle, then due to length-bias, the enrollment cycle will be stochastically larger than the general run of cycles, a typical property of prevalent cohort studies. Furthermore, the probability of enrollment can depend on the length of time since a woman's last menstrual period (a backward recurrence time), resulting in selection effects. We focus on accounting for length-bias and selection effects in the likelihood for enrollment menstrual cycle length, using a recursive two-stage approach wherein we first estimate the probability of enrollment as a function of the backward recurrence time and then use it in a likelihood with sampling weights that account for length-bias and selection effects. To broaden the applicability of our methods, we augment our model to incorporate a couple-specific random effect and time-independent covariate. A simulation study quantifies performance for two scenarios of enrollment probability when proper account is taken of sampling plan features. In addition, we estimate the probability of enrollment and the distribution of menstrual cycle length for the study population of the Longitudinal Investigation of Fertility and the Environment Study.
C1 [Lum, Kirsten J.; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, DHHS, Rockville, MD 20852 USA.
[Lum, Kirsten J.; Louis, Thomas A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
[Louis, Thomas A.] US Bur Census, Suitland, MD 20746 USA.
RP Louis, TA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
EM tlouis@jhu.edu
OI Sundaram, Rajeshwari/0000-0002-6918-5002
FU Intramural Research Program of the U.S., National Institutes of Health,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358]; U.S.,
National Institutes of Health, National Institute of Environmental
Health Sciences [Training Grant] [2T32ES012871]
FX This work was supported by the Intramural Research Program of the U.S.,
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [Contracts N01-HD-3-3355,
N01-HD-3-3356, N01-HD-3-3358] and by the U.S., National Institutes of
Health, National Institute of Environmental Health Sciences [Training
Grant 2T32ES012871].
NR 26
TC 3
Z9 3
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2015
VL 16
IS 1
BP 113
EP 128
DI 10.1093/biostatistics/kxu035
PG 16
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA AY2JZ
UT WOS:000347417500011
PM 25027273
ER
PT J
AU Song, MS
Kraft, P
Joshi, AD
Barrdahl, M
Chatterjee, N
AF Song, Minsun
Kraft, Peter
Joshi, Amit D.
Barrdahl, Myrto
Chatterjee, Nilanjan
TI Testing calibration of risk models at extremes of disease risk
SO BIOSTATISTICS
LA English
DT Article
DE Case-control studies; Gene-gene and gene-environment interactions;
Genome-wide association studies; Goodness-of-fit tests; Polygenic score;
Risk stratification
ID ASSOCIATION; PERFORMANCE; PREDICTION; VARIANTS; BREAST
AB Risk-prediction models need careful calibration to ensure they produce unbiased estimates of risk for subjects in the underlying population given their risk-factor profiles. As subjects with extreme high or low risk may be the most affected by knowledge of their risk estimates, checking the adequacy of risk models at the extremes of risk is very important for clinical applications. We propose a new approach to test model calibration targeted toward extremes of disease risk distribution where standard goodness-of-fit tests may lack power due to sparseness of data. We construct a test statistic based on model residuals summed over only those individuals who pass high and/or low risk thresholds and then maximize the test statistic over different risk thresholds. We derive an asymptotic distribution for the max-test statistic based on analytic derivation of the variance-covariance function of the underlying Gaussian process. The method is applied to a large case-control study of breast cancer to examine joint effects of common single nucleotide polymorphisms (SNPs) discovered through recent genome-wide association studies. The analysis clearly indicates a non-additive effect of the SNPs on the scale of absolute risk, but an excellent fit for the linear-logistic model even at the extremes of risks.
C1 [Song, Minsun; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Kraft, Peter; Joshi, Amit D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Barrdahl, Myrto] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
EM chattern@mail.nih.gov
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics of the National Cancer Institute; U.S. National Institutes of
Health, National Cancer Institute [U01-CA98233, U19-CA148065,
U01-CA98710, U01-CA98216, U01-CA98758]; U.S. National Institutes of
Health, National Cancer Institute (Intramural Research Program of
NIH/NCI, Division of Cancer Epidemiology and Genetics)
FX Drs M.S. and N.C.'s research was supported by the Intramural Research
Program of the Division of Cancer Epidemiology and Genetics of the
National Cancer Institute. The breast cancer dataset was funded by the
U.S. National Institutes of Health, National Cancer Institute
(cooperative agreements U01-CA98233 and U19-CA148065 to David J. Hunter,
U01-CA98710 to Michael J. Thun, U01-CA98216 to Elio Riboli and Rudolf
Kaaks, and U01-CA98758 to Brian E. Henderson, and Intramural Research
Program of NIH/NCI, Division of Cancer Epidemiology and Genetics).
NR 16
TC 5
Z9 5
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2015
VL 16
IS 1
BP 143
EP 154
DI 10.1093/biostatistics/kxu034
PG 12
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA AY2JZ
UT WOS:000347417500013
PM 25027274
ER
PT J
AU Shardell, M
Hicks, GE
Ferrucci, L
AF Shardell, Michelle
Hicks, Gregory E.
Ferrucci, Luigi
TI Doubly robust estimation and causal inference in longitudinal studies
with dropout and truncation by death
SO BIOSTATISTICS
LA English
DT Article
DE Causal inference; Longitudinal data analysis; Missing data;
Observational studies
ID MARGINAL STRUCTURAL MODELS; VITAMIN-D DEFICIENCY; MISSING DATA;
HYPOTHETICAL INTERVENTIONS; PRINCIPAL STRATIFICATION;
POST-RANDOMIZATION; OUTCOMES; MORTALITY; EPIDEMIOLOGY; GUIDELINE
AB Motivated by aging research, we propose an estimator of the effect of a time-varying exposure on an outcome in longitudinal studies with dropout and truncation by death. We use an inverse-probability weighted (IPW) estimator to derive a doubly robust augmented inverse-probability weighted (AIPW) estimator. IPW estimation involves weights for the exposure mechanism, dropout, and mortality; AIPW estimation additionally involves estimating data-generating models via regression. We demonstrate that the estimators identify a causal contrast that is a function of principal strata effects under a set of assumptions. Simulations show that AIPW estimation is unbiased when weights or outcome regressions are correct, and that AIPW estimation is more efficient than IPW estimation when all models are correct. We apply the method to a study of vitamin D and gait speed among older adults.
C1 [Shardell, Michelle] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA.
[Ferrucci, Luigi] NIA, Baltimore, MD 21225 USA.
RP Shardell, M (reprint author), Univ Maryland, Dept Epidemiol & Publ Hlth, 660 West Redwood St, Baltimore, MD 21201 USA.
EM mshardel@epi.umaryland.edu
FU National Institutes of Health [K25AG034216, R01AG041202]
FX This work was supported by the National Institutes of Health
(K25AG034216, R01AG041202).
NR 46
TC 4
Z9 4
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2015
VL 16
IS 1
BP 155
EP 168
DI 10.1093/biostatistics/kxu032
PG 14
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA AY2JZ
UT WOS:000347417500014
PM 24997309
ER
PT J
AU Li, Y
Safaeian, M
Robbins, HA
Graubard, BI
AF Li, Yan
Safaeian, Mahboobeh
Robbins, Hilary A.
Graubard, Barry I.
TI Logistic analysis of epidemiologic studies with augmentation sampling
involving re-stratification and population expansion
SO BIOSTATISTICS
LA English
DT Article
DE Pseudo-likelihood function; Sample weighting; Taylor linearization
variance estimation; Two-stage stratified sampling
ID DUAL FRAME SURVEYS; HUMAN-PAPILLOMAVIRUS; COSTA-RICA; DESIGN; INFECTION
AB Epidemiologic cross-sectional, case-cohort, or case-control studies often select augmentation samples to supplement an existing (baseline) sample, primarily for the two reasons: (1) to increase the sample sizes from certain subdomains of interest that were not originally considered in the design of the baseline study and (2) to obtain samples from an extension of the target population. To address these two objectives, two-stage stratified sample designs are considered, where the stratification based on the expanded population at the second stage is not nested in the first stage strata. The sample weighting and Taylor linearization variance estimation for the two-stage stratified sample designs, involving re-stratification and population expansion, are provided for estimating population totals and logistic regression coefficients. Results from limited simulation studies and a logistic regression analysis of a study of human papillomavirus serology are provided.
C1 [Li, Yan] Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA.
[Safaeian, Mahboobeh; Robbins, Hilary A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Li, Y (reprint author), Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA.
EM yli6@umd.edu
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute at the National Institutes of Health.
NR 17
TC 0
Z9 0
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
EI 1468-4357
J9 BIOSTATISTICS
JI Biostatistics
PD JAN
PY 2015
VL 16
IS 1
BP 169
EP 178
DI 10.1093/biostatistics/kxu024
PG 10
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA AY2JZ
UT WOS:000347417500015
PM 24907707
ER
PT J
AU Markt, SC
Valdimarsdottir, UA
Shui, IM
Sigurdardottir, LG
Rider, JR
Tamimi, RM
Batista, JL
Haneuse, S
Flynn-Evans, E
Lockley, SW
Czeisler, CA
Stampfer, MJ
Launer, L
Harris, T
Smith, AV
Gudnason, V
Lindstrom, S
Kraft, P
Mucci, LA
AF Markt, Sarah C.
Valdimarsdottir, Unnur A.
Shui, Irene M.
Sigurdardottir, Lara G.
Rider, Jennifer R.
Tamimi, Rulla M.
Batista, Julie L.
Haneuse, Sebastien
Flynn-Evans, Erin
Lockley, Steven W.
Czeisler, Charles A.
Stampfer, Meir J.
Launer, Lenore
Harris, Tamara
Smith, Albert Vernon
Gudnason, Vilmundur
Lindstrom, Sara
Kraft, Peter
Mucci, Lorelei A.
TI Circadian clock genes and risk of fatal prostate cancer
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Circadian genes; Prostate cancer; Genetic polymorphisms
ID GENOME-WIDE ASSOCIATION; SHIFT-WORK; GENOTOXIC STRESS; TUMOR-SUPPRESSOR;
DISRUPTION; VARIANTS; NPAS2; MEN; EPIDEMIOLOGY; CYCLE
AB Circadian genes may be involved in regulating cancer-related pathways, including cell proliferation, DNA damage response, and apoptosis. We aimed to assess the role of genetic variation in core circadian rhythm genes with the risk of fatal prostate cancer and first morning void urinary 6-sulfatoxymelatonin levels.
We used unconditional logistic regression to evaluate the association of 96 single-nucleotide polymorphisms (SNPs) across 12 circadian-related genes with fatal prostate cancer in the AGES-Reykjavik cohort (n = 24 cases), the Health Professionals Follow-Up Study (HPFS) (n = 40 cases), and the Physicians' Health Study (PHS) (n = 105 cases). We used linear regression to evaluate the association between SNPs and first morning void urinary 6-sulfatoxymelatonin levels in AGES-Reykjavik. We used a kernel machine test to evaluate whether multimarker SNP sets in the pathway (gene based) were associated with our outcomes.
None of the individual SNPs were consistently associated with fatal prostate cancer across the three cohorts. In each cohort, gene-based analyses showed that variation in the CRY1 gene was nominally associated with fatal prostate cancer (p values = 0.01, 0.01, and 0.05 for AGES-Reykjavik, HPFS, and PHS, respectively). In AGES-Reykjavik, SNPs in TIMELESS (four SNPs), NPAS2 (six SNPs), PER3 (two SNPs) and CSNK1E (one SNP) were nominally associated with 6-sulfatoxymelatonin levels.
We did not find a strong and consistent association between variation in core circadian clock genes and fatal prostate cancer risk, but observed nominally significant gene-based associations with fatal prostate cancer and 6-sulfatoxymelatonin levels.
C1 [Markt, Sarah C.; Valdimarsdottir, Unnur A.; Shui, Irene M.; Rider, Jennifer R.; Tamimi, Rulla M.; Batista, Julie L.; Stampfer, Meir J.; Lindstrom, Sara; Kraft, Peter; Mucci, Lorelei A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Valdimarsdottir, Unnur A.; Sigurdardottir, Lara G.; Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Valdimarsdottir, Unnur A.; Sigurdardottir, Lara G.; Mucci, Lorelei A.] Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland.
[Sigurdardottir, Lara G.] Iceland Canc Soc, Reykjavik, Iceland.
[Rider, Jennifer R.; Tamimi, Rulla M.; Batista, Julie L.; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Haneuse, Sebastien; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Flynn-Evans, Erin; Lockley, Steven W.; Czeisler, Charles A.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA.
[Flynn-Evans, Erin; Lockley, Steven W.; Czeisler, Charles A.] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA.
[Launer, Lenore; Harris, Tamara] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
RP Markt, SC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM sec110@mail.harvard.edu
RI Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Smith,
Albert/0000-0003-1942-5845; Rider, Jennifer/0000-0002-2637-6036
FU National Institutes on Aging Intramural Research Program [N01-AG-12100];
Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic
Parliament); Harvard Catalyst Award; Icelandic Cancer Society; National
Cancer Institute at the National Institutes of Health [P01 CA055075,
CA133891, CA42182, CA34944, CA40360, CA141298, CA98233, CA097193];
National Heart, Lung, and Blood Institute at the National Institutes of
Health [HL26490, HL34595]; National Cancer Institute at the National
Institutes of Health Training Grant [R25 CA098566, T32 CA09001-35]; US
Army Department of Defense Prostate Cancer Research Program Fellowship;
NIH NIA [P01-AG-009975]
FX We thank the study participants and the Icelandic Heart Association
clinic staff for their invaluable contribution. We are grateful to the
ongoing participation of men in the Health Professionals Follow-up Study
(UM1 CA167552) and would like to acknowledge our colleagues (Lauren
McLaughlin and Siobhan Saint-Surin) working on these studies for their
valuable help. In addition, we would like to thank the following state
cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA,
ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK,
OR, PA, RI, SC, TN, TX, VA, WA, and WY. The AGES-Reykjavik is supported
by Contract N01-AG-12100 from the National Institutes on Aging
Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); and the Althingi (the Icelandic Parliament). In addition,
this study was supported by funding from the Harvard Catalyst Award, the
Icelandic Cancer Society, the National Cancer Institute at the National
Institutes of Health (P01 CA055075, CA133891, CA42182, CA34944, CA40360,
CA141298, CA98233 and CA097193); the National Heart, Lung, and Blood
Institute at the National Institutes of Health (HL26490, HL34595).
National Cancer Institute at the National Institutes of Health Training
Grant (R25 CA098566 and T32 CA09001-35 to SCM); and the Prostate Cancer
Foundation (to LAM and JRR); US Army Department of Defense Prostate
Cancer Research Program Fellowship (to IMS). CAC was supported in part
by NIH NIA Grant P01-AG-009975.
NR 40
TC 5
Z9 5
U1 1
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JAN
PY 2015
VL 26
IS 1
BP 25
EP 33
DI 10.1007/s10552-014-0478-z
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AY0JA
UT WOS:000347281800003
PM 25388799
ER
PT J
AU Nyante, SJ
Gammon, MD
Kaufman, JS
Bensen, JT
Lin, DY
Barnholtz-Sloan, JS
Hu, YJ
He, QC
Luo, JC
Millikan, RC
AF Nyante, Sarah J.
Gammon, Marilie D.
Kaufman, Jay S.
Bensen, Jeannette T.
Lin, Dan Yu
Barnholtz-Sloan, Jill S.
Hu, Yijuan
He, Qianchuan
Luo, Jingchun
Millikan, Robert C.
TI Genetic variation in estrogen and progesterone pathway genes and breast
cancer risk: an exploration of tumor subtype-specific effects
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Single nucleotide polymorphisms; Estrogen receptor;
Progesterone receptor; Cytochrome P450 family 19 subfamily A polypeptide
1; 17-Beta hydroxysteroid dehydrogenase type II; Sex hormone-binding
globulin; 3-Beta hydroxysteroid dehydrogenase type I
ID GENOME-WIDE ASSOCIATION; BASAL-LIKE SUBTYPE; SUSCEPTIBILITY LOCI;
POPULATION STRATIFICATION; LINKAGE DISEQUILIBRIUM; COMMON VARIANTS;
HUMAN AROMATASE; RECEPTOR; POLYMORPHISM; CELLS
AB To determine whether associations between estrogen pathway-related single nucleotide polymorphisms (SNPs) and breast cancer risk differ by molecular subtype, we evaluated associations between SNPs in cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1), estrogen receptor (ESR1), 3-beta hydroxysteroid dehydrogenase type I (HSD3B1), 17-beta hydroxysteroid dehydrogenase type II (HSD17B2), progesterone receptor (PGR), and sex hormone-binding globulin (SHBG) and breast cancer risk in a case-control study in North Carolina.
Cases (n = 1,972) were women 20-74 years old and diagnosed with breast cancer between 1993 and 2001. Population-based controls (n = 1,776) were frequency matched to cases by age and race. A total of 195 SNPs were genotyped, and linkage disequilibrium was evaluated using the r (2) statistic. Odds ratios (ORs) and 95 % confidence intervals (CIs) for associations with breast cancer overall and by molecular subtype were estimated using logistic regression. Monte Carlo methods were used to control for multiple comparisons; two-sided p values < 3.3 x 10(-4) were statistically significant. Heterogeneity tests comparing the two most common subtypes, luminal A (n = 679) and basal-like (n = 200), were based on the Wald statistic.
ESR1 rs6914211 (AA vs. AT+TT, OR 2.24, 95 % CI 1.51-3.33), ESR1 rs985191 (CC vs. AA, OR 2.11, 95 % CI 1.43-3.13), and PGR rs1824128 (TT+GT vs. GG, OR 1.33, 95 % CI 1.14-1.55) were associated with risk after accounting for multiple comparisons. Rs6914211 and rs985191 were in strong linkage disequilibrium among controls (African-Americans r (2) = 0.70; whites r (2) = 0.95). There was no evidence of heterogeneity between luminal A and basal-like subtypes, and the three SNPs were also associated with elevated risk of the less common luminal B, HER2+/ER-, and unclassified subtypes.
ESR1 and PGR SNPs were associated with risk, but lack of heterogeneity between subtypes suggests variants in hormone-related genes may play similar roles in the etiology of breast cancer molecular subtypes.
C1 [Nyante, Sarah J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gammon, Marilie D.; Bensen, Jeannette T.; Millikan, Robert C.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Gammon, Marilie D.; Bensen, Jeannette T.; Lin, Dan Yu; Luo, Jingchun; Millikan, Robert C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Kaufman, Jay S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Lin, Dan Yu; Hu, Yijuan] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Barnholtz-Sloan, Jill S.] Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH USA.
[He, Qianchuan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Nyante, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM nyantesj@mail.nih.gov
OI Kaufman, Jay/0000-0003-1606-401X
FU National Institutes of Health [P50-CA58223, P30-CA16086, R25-CA57726,
P30ES10126]
FX This work was supported by funding from the National Institutes of
Health [P50-CA58223, P30-CA16086, R25-CA57726 to S.J.N., P30ES10126 to
M. D. G. and R. C. M.]. The authors wish to thank Patricia Basta of the
University of North Carolina at Chapel Hill Epidemiology Department, and
Michael Andre and Amanda Beaty of the University of North Carolina
Lineberger Comprehensive Cancer Center for their work preparing the DNA
samples and conducting the genotyping. The authors also thank Jessica
Tse of the University of North Carolina at Chapel Hill Epidemiology
Department for advice and statistical support.
NR 62
TC 1
Z9 1
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JAN
PY 2015
VL 26
IS 1
BP 121
EP 131
DI 10.1007/s10552-014-0491-2
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AY0JA
UT WOS:000347281800012
PM 25421376
ER
PT J
AU Warrington, NM
Sun, T
Luo, JQ
McKinstry, RC
Parkin, PC
Ganzhorn, S
Spoljaric, D
Albers, AC
Merkelson, A
Stewart, DR
Stevenson, DA
Viskochil, D
Druley, TE
Forys, JT
Reilly, KM
Fisher, MJ
Tabori, U
Allen, JC
Schiffman, JD
Gutmann, DH
Rubin, JB
AF Warrington, Nicole M.
Sun, Tao
Luo, Jingqin
McKinstry, Robert C.
Parkin, Patricia C.
Ganzhorn, Sara
Spoljaric, Debra
Albers, Anne C.
Merkelson, Amanda
Stewart, Douglas R.
Stevenson, David A.
Viskochil, David
Druley, Todd E.
Forys, Jason T.
Reilly, Karlyne M.
Fisher, Michael J.
Tabori, Uri
Allen, Jeffrey C.
Schiffman, Joshua D.
Gutmann, David H.
Rubin, Joshua B.
TI The Cyclic AMP Pathway Is a Sex-Specific Modifier of Glioma Risk in Type
I Neurofibromatosis Patients
SO CANCER RESEARCH
LA English
DT Article
ID VISUAL-ACUITY; FOLLOW-UP; CHILDREN; TUMORS; MANIFESTATIONS; ASSOCIATION;
EXPRESSION; BRAIN; MODEL
AB Identifying modifiers of glioma risk in patients with type I neurofibromatosis (NF1) could help support personalized tumor surveillance, advance understanding of gliomagenesis, and potentially identify novel therapeutic targets. Here, we report genetic polymorphisms in the human adenylate cyclase gene adenylate cyclase 8 (ADCY8) that correlate with glioma risk in NF1 in a sex-specific manner, elevating risk in females while reducing risk in males. This finding extends earlier evidence of a role for cAMP in gliomagenesis based on results in a genetically engineered mouse model (Nf1 GEM). Thus, sexually dimorphic cAMP signaling might render males and females differentially sensitive to variation in cAMP levels. Using male and female Nf1 GEM, we found significant sex differences exist in cAMP regulation and in the growth-promoting effects of cAMP suppression. Overall, our results establish a sex-specific role for cAMP regulation in human gliomagenesis, specifically identifying ADCY8 as a modifier of glioma risk in NF1. (C)2014 AACR.
C1 [Warrington, Nicole M.; Sun, Tao; McKinstry, Robert C.; Ganzhorn, Sara; Spoljaric, Debra; Druley, Todd E.; Forys, Jason T.; Rubin, Joshua B.] Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA.
[Luo, Jingqin] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[McKinstry, Robert C.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Parkin, Patricia C.] Univ Toronto, Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Albers, Anne C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Merkelson, Amanda] NYU, Langone Med Ctr, Dept Pediat, New York, NY USA.
[Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Stewart, Douglas R.] Univ Utah, Div Med Genet, Salt Lake City, UT USA.
[Stevenson, David A.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Reilly, Karlyne M.] NCI, Ctr Canc Res, Off Director, Rare Tumors Initiat, Bethesda, MD USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA USA.
[Rubin, Joshua B.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Rubin, Joshua B.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
RP Rubin, JB (reprint author), Washington Univ, Sch Med, Campus Box 8208,660 South Euclid Ave, St Louis, MO 63110 USA.
EM rubin_j@kids.wustl.edu
FU Children's Discovery Institute of Washington University; NCI
[RO1-CA136573, UO1-CA141549]; NIH [UL1RR025764]; DOD [W81XWH-11-1-0250];
Children's Tumor Foundation; Hospital for Sick Children Research
Institute; University of Utah; Division of Cancer Epidemiology and
Genetics of the National Cancer Institute; NCI Cancer Center [P30
CA91842]; ICTS/CTSA from the National Center for Research Resources
(NCRR), a component of the NIH [UL1TR000448]; NIH, NCI [IRP ZIA BC
010539]; NIH Roadmap for Medical Research
FX This work was supported by grants from The Children's Discovery
Institute of Washington University (J.B. Rubin and D.H. Gutmann), the
NCI RO1-CA136573 (J.B. Rubin and D.H. Gutmann), UO1-CA141549 (D.H.
Gutmann), the NIH UL1RR025764 (D.A. Stevenson), The DOD W81XWH-11-1-0250
(D.A. Stevenson), Children's Tumor Foundation Young Investigator Award
(T. Sun), IRP ZIA BC 010539 of the NIH, NCI (K.M. Reilly), The Hospital
for Sick Children Research Institute (P.C. Parkin), the University of
Utah Clinical Genetics Research Program (D.A. Stevenson). D.R. Stewart
was supported, in part, by the intramural program of the Division of
Cancer Epidemiology and Genetics of the National Cancer Institute. The
Genome Technology Access Center in the Department of Genetics at
Washington University School of Medicine helped with genomic analysis
and is partially supported by NCI Cancer Center Support Grant #P30
CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1TR000448
from the National Center for Research Resources (NCRR), a component of
the NIH, and NIH Roadmap for Medical Research.
NR 29
TC 13
Z9 13
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 1
PY 2015
VL 75
IS 1
BP 16
EP 21
DI 10.1158/0008-5472.CAN-14-1891
PG 6
WC Oncology
SC Oncology
GA AY1XN
UT WOS:000347383000004
PM 25381154
ER
PT J
AU Boggs, AE
Vitolo, MI
Whipple, RA
Charpentier, MS
Goloubeva, OG
Ioffe, OB
Tuttle, KC
Slovic, J
Lu, YL
Mills, GB
Martin, SS
AF Boggs, Amanda E.
Vitolo, Michele I.
Whipple, Rebecca A.
Charpentier, Monica S.
Goloubeva, Olga G.
Ioffe, Olga B.
Tuttle, Kimberly C.
Slovic, Jana
Lu, Yiling
Mills, Gordon B.
Martin, Stuart S.
TI alpha-Tubulin Acetylation Elevated in Metastatic and Basal-like Breast
Cancer Cells Promotes Microtentacle Formation, Adhesion, and Invasive
Migration
SO CANCER RESEARCH
LA English
DT Article
ID CIRCULATING TUMOR-CELLS; ACETYLTRANSFERASE; EXPRESSION; CYTOSKELETON;
HDAC6; MICROTUBULES; SUBTYPES; SURVIVAL; MEC-17; REATTACHMENT
AB Metastatic cases of breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of alpha-tubulin acetylation are a sufficient cause of metastatic potential in breast cancer. In suspended cell culture conditions, metastatic breast cancer cells exhibited high alpha-tubulin acetylation levels that extended along microtentacle (McTN) protrusions. Mutation of the acetylation site on alpha-tubulin and enzymatic modulation of this posttranslational modification exerted a significant impact on McTN frequency and the reattachment of suspended tumor cells. Reducing alpha-tubulin acetylation significantly inhibited migration but did not affect proliferation. In an analysis of more than 140 matched primary and metastatic tumors from patients, we found that acetylation was maintained and in many cases increased in lymph node metastases compared with primary tumors. Proteomic analysis of an independent cohort of more than 390 patient specimens further documented the relationship between increased alpha-tubulin acetylation and the aggressive behaviors of basal-like breast cancers, with a trend toward increased risk of disease progression and death in patients with high-intensity alpha-tubulin acetylation in primary tumors. Taken together, our results identify a tight correlation between acetylated alpha-tubulin levels and aggressive metastatic behavior in breast cancer, with potential implications for the definition of a simple prognostic biomarker in patients with breast cancer. (C) 2014 AACR.
C1 [Boggs, Amanda E.; Vitolo, Michele I.; Charpentier, Monica S.; Slovic, Jana; Martin, Stuart S.] Univ Maryland, Grad Program Life Sci, Baltimore, MD 21201 USA.
[Boggs, Amanda E.; Vitolo, Michele I.; Whipple, Rebecca A.; Charpentier, Monica S.; Slovic, Jana; Martin, Stuart S.] Univ Maryland, Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
[Vitolo, Michele I.; Martin, Stuart S.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
[Goloubeva, Olga G.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Ioffe, Olga B.; Tuttle, Kimberly C.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Lu, Yiling; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
RP Martin, SS (reprint author), Univ Maryland, Sch Med, Dept Physiol, Marlene & Stewart Greenebaum NCI Canc Ctr, 655 W Baltimore St,Bressler Bldg,Room 10-029, Baltimore, MD 21201 USA.
EM ssmartin@som.umaryland.edu
FU National Cancer Institute [R01-CA154624, R01-124704]; Susan G. Komen
Foundation [KG100240]; Department of Defense [BC100675]; NIH grant
[K01-CA166576]
FX This research is supported by R01-CA154624 and R01-124704 from the
National Cancer Institute, KG100240 from the Susan G. Komen Foundation,
and an Era of Hope Scholar Award from the Department of Defense
(BC100675). M.I. Vitolo is supported by NIH grant K01-CA166576.
NR 57
TC 15
Z9 15
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JAN 1
PY 2015
VL 75
IS 1
BP 203
EP 215
DI 10.1158/0008-5472.CAN-13-3563
PG 13
WC Oncology
SC Oncology
GA AY1XN
UT WOS:000347383000021
PM 25503560
ER
PT J
AU Raft, S
Groves, AK
AF Raft, Steven
Groves, Andrew K.
TI Segregating neural and mechanosensory fates in the developing ear:
patterning, signaling, and transcriptional control
SO CELL AND TISSUE RESEARCH
LA English
DT Review
DE Inner ear; Neurogenesis; Sensory cells; Transcription factors; Induction
ID MAMMALIAN INNER-EAR; HAIR-CELL-DIFFERENTIATION; DEVELOPING
NERVOUS-SYSTEM; DEVELOPING DROSOPHILA EYE; SENSORY ORGAN DEVELOPMENT;
ADULT ABDOMINAL SEGMENTS; MIND-BOMB MUTANT; OTIC PLACODE; IN-VIVO;
SUPPORTING CELLS
AB The vertebrate inner ear is composed of multiple sensory receptor epithelia, each of which is specialized for detection of sound, gravity, or angular acceleration. Each receptor epithelium contains mechanosensitive hair cells, which are connected to the brainstem by bipolar sensory neurons. Hair cells and their associated neurons are derived from the embryonic rudiment of the inner ear epithelium, but the precise spatial and temporal patterns of their generation, as well as the signals that coordinate these events, have only recently begun to be understood. Gene expression, lineage tracing, and mutant analyses suggest that both neurons and hair cells are generated from a common domain of neural and sensory competence in the embryonic inner ear rudiment. Members of the Shh, Wnt, and FGF families, together with retinoic acid signals, regulate transcription factor genes within the inner ear rudiment to establish the axial identity of the ear and regionalize neurogenic activity. Close-range signaling, such as that of the Notch pathway, specifies the fate of sensory regions and individual cell types. We also describe positive and negative interactions between basic helix-loop-helix and SoxB family transcription factors that specify either neuronal or sensory fates in a context-dependent manner. Finally, we review recent work on inner ear development in zebrafish, which demonstrates that the relative timing of neurogenesis and sensory epithelial formation is not phylogenetically constrained.
C1 [Raft, Steven] NIDCD, Sect Sensory Cell Regenerat & Dev, NIH, Bethesda, MD 20892 USA.
[Groves, Andrew K.] Baylor Coll Med, Program Dev Biol, Dept Neurosci, Houston, TX 77030 USA.
[Groves, Andrew K.] Baylor Coll Med, Program Dev Biol, Dept Mol & Human Genet, Houston, TX 77030 USA.
RP Groves, AK (reprint author), Baylor Coll Med, Program Dev Biol, Dept Neurosci, 1 Baylor Plaza, Houston, TX 77030 USA.
EM rafts@nidcd.nih.gov; akgroves@bcm.edu
OI Groves, Andrew/0000-0002-0784-7998
FU NIDCD NIH HHS [R01 DC006185]
NR 173
TC 12
Z9 12
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0302-766X
EI 1432-0878
J9 CELL TISSUE RES
JI Cell Tissue Res.
PD JAN
PY 2015
VL 359
IS 1
BP 315
EP 332
DI 10.1007/s00441-014-1917-6
PG 18
WC Cell Biology
SC Cell Biology
GA AY2FJ
UT WOS:000347403700023
PM 24902666
ER
PT J
AU Gamrekelashvili, J
Greten, TF
Korangy, F
AF Gamrekelashvili, Jaba
Greten, Tim F.
Korangy, Firouzeh
TI Immunogenicity of necrotic cell death
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Cell death; Peptidase; Immunogenic cell death; Cancer vaccine; CD8(+) T
cell
ID MHC CLASS-I; HEAT-SHOCK PROTEINS; CD8(+) T-CELLS; ANTIGEN-PROCESSING
PATHWAY; INNATE IMMUNE-RESPONSES; APOPTOTIC TUMOR-CELLS; THIMET
OLIGOPEPTIDASE; DENDRITIC CELLS; PROINFLAMMATORY CYTOKINE; CALRETICULIN
EXPOSURE
AB The mode of tumor cell death has significant effects on anti-tumor immunity. Although, previously it was thought that cell death is an inert effect, different investigators have clearly shown that dying tumors can attract, activate and mature professional antigen presenting cells and dendritic cells. In addition, others and we have shown that the type of tumor cell death not only controls the presence or absence of specific tumor antigens, but also can result in immunological responses ranging from immunosuppression to anti-tumor immunity. More importantly, it is possible to enhance anti-tumor immunity both in vitro and in vivo by targeting specific molecular mechanisms such as oligopeptidases and the proteasome. These studies not only extend our knowledge on basic immunological questions and the induction of anti-tumor immunity, but also have implications for all types of cancer treatments, in which rapid tumor cell death is induced. This review is a comprehensive summary of cell death and particularly necrosis and the pivotal role it plays in anti-tumor immunity.
C1 [Gamrekelashvili, Jaba] Hannover Med Sch, Dept Nephrol, D-30623 Hannover, Germany.
[Greten, Tim F.; Korangy, Firouzeh] NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res,NIH,CCR, Bethesda, MD 20892 USA.
RP Greten, TF (reprint author), NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res,NIH,CCR, Bldg 10 Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov; firouzeh.korangy@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU NCI, NIH
FX This work was supported by the Intramural Research Program of the NCI,
NIH.
NR 116
TC 1
Z9 2
U1 2
U2 8
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JAN
PY 2015
VL 72
IS 2
BP 273
EP 283
DI 10.1007/s00018-014-1741-x
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AY2FL
UT WOS:000347404000005
PM 25274062
ER
PT J
AU Reis, J
Fischer, JT
Prichard, G
Weiller, C
Cohen, LG
Fritsch, B
AF Reis, Janine
Fischer, Jan Torben
Prichard, George
Weiller, Cornelius
Cohen, Leonardo G.
Fritsch, Brita
TI Time- but Not Sleep-Dependent Consolidation of tDCS-Enhanced Visuomotor
Skills
SO CEREBRAL CORTEX
LA English
DT Article
DE cortical excitability; motor skill learning; noninvasive brain
stimulation; warm-up decrement
ID DIRECT-CURRENT STIMULATION; WARM-UP DECREMENT; PRIMARY MOTOR CORTEX;
PROCEDURAL CONSOLIDATION; PREMOTOR CORTEX; SEQUENCE; PLASTICITY; MEMORY;
PERFORMANCE; HUMANS
AB Consolidation of motor skills after training can occur in a time- or sleep-dependent fashion. Recent studies revealed time-dependent consolidation as a common feature of visuomotor tasks. We have previously shown that anodal transcranial direct current stimulation (tDCS) in combination with repeated motor training benefits consolidation by the induction of offline skill gains in a complex visuomotor task, preventing the regular occurrence of skill loss between days. Here, we asked 2 questions: What is the time course of consolidation between days for this task and do exogenously induced offline gains develop as a function of time or overnight sleep? We found that both the development of offline skill loss in sham-stimulated subjects and offline skill gains induced by anodal tDCS critically depend on the passage of time after training, but not on overnight sleep. These findings support the view that tDCS interacts directly with the physiological consolidation process. However, in a control experiment, anodal tDCS applied after the training did not induce skill gains, implying that coapplication of tDCS and training is required to induce offline skill gains, pointing to the initiation of consolidation already during training.
C1 [Reis, Janine; Fischer, Jan Torben; Prichard, George; Weiller, Cornelius; Fritsch, Brita] Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany.
[Prichard, George] UCL London, Inst Cognit Neurosci, London, England.
[Cohen, Leonardo G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
RP Reis, J (reprint author), Univ Freiburg, Dept Neurol, Breisacher Str 64, D-79106 Freiburg, Germany.
EM janine.reis@uniklinik-freiburg.de
OI Fritsch, Brita/0000-0003-4884-9049
FU Alexander-von-Humboldt-Foundation; NINDS Intramural Program; Neurex
Support Program for welcome/coming back of researchers
FX This work was supported by a personal grant of the
Alexander-von-Humboldt-Foundation and the NINDS Intramural Program (J.R.
and L.G.C.) as well as the Neurex Support Program for welcome/coming
back of researchers (J.R. and B.F.).
NR 53
TC 19
Z9 20
U1 1
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JAN
PY 2015
VL 25
IS 1
BP 109
EP 117
DI 10.1093/cercor/bht208
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA AY2KA
UT WOS:000347417600011
PM 23960213
ER
PT J
AU Taveira-DaSilva, AM
Jones, AM
Julien-Williams, PA
Stylianou, M
Moss, J
AF Taveira-DaSilva, Angelo M.
Jones, Amanda M.
Julien-Williams, Patricia A.
Stylianou, Mario
Moss, Joel
TI Retrospective Review of Combined Sirolimus and Simvastatin Therapy in
Lymphangioleiomyomatosis
SO CHEST
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; GIANT-CELL ASTROCYTOMAS; GROWTH CONTROL;
GENE-PRODUCTS; LUNG-FUNCTION; ATORVASTATIN; EVEROLIMUS; MTOR; RHEB; TSC2
AB BACKGROUND: Combined simvastatin and sirolimus therapy reduces tuberous sclerosis complex 2-null lesions and alveolar destruction in a mouse model of lymphangioleiomyomatosis (LAM), suggesting that therapy with both drugs may benefit patients with LAM.
METHODS: To determine whether simvastatin changed the prevalence of adverse events or altered the therapeutic effects of sirolimus, we recorded adverse events and changes in lung function in patients with LAM treated with simvastatin plus sirolimus (n = 14), sirolimus alone (n = 44), or simvastatin alone (n = 20).
RESULTS: Sirolimus-related adverse events in the simvastatin plus sirolimus and sirolimus-only groups were 64% and 66% for stomatitis, 50% and 52% for diarrhea, 50% and 45% for peripheral edema, 36% and 61% for acne, 36% and 30% for hypertension, 29% and 27% for proteinuria, 29% and 27% for leukopenia, and 21% and 27% for hypercholesterolemia. The frequency of simvastatin-related adverse events in the simvastatin-only and simvastatin plus sirolimus groups were 60% and 50% for arthralgias and 35% and 36% for myopathy. Before simvastatin plus sirolimus therapy, FEV1 and diffusing capacity of the lung for carbon monoxide (D-LCO) yearly rates of change were, respectively, -1.4 +/- 0.2 and -1.8 +/- 0.2% predicted. After simvastatin plus sirolimus therapy, these rates changed to +1.2 +/- 0.5 (P = .635) and +0.3 +/- 0.4% predicted (P = .412), respectively. In 44 patients treated with sirolimus alone, FEV1 and D-LCO rates of change were -1.7 +/- 0.1 and -2.2 +/- 0.1% predicted before treatment and +1.7 +/- 0.3 and +0.7 +/- 0.3% predicted after treatment (P<.001).
CONCLUSIONS: Therapy with sirolimus and simvastatin does not increase the prevalence of drug adverse events or alter the therapeutic effects of sirolimus.
C1 [Taveira-DaSilva, Angelo M.; Jones, Amanda M.; Julien-Williams, Patricia A.; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Stylianou, Mario] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D03,MSC 1590, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
FU Intramural Research Program, National Institutes of Health, National
Heart, Lung, and Blood Institute
FX This study was supported by the Intramural Research Program, National
Institutes of Health, National Heart, Lung, and Blood Institute.
NR 32
TC 4
Z9 5
U1 0
U2 5
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JAN
PY 2015
VL 147
IS 1
BP 180
EP 187
DI 10.1378/chest.14-0758
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AY3AH
UT WOS:000347456500037
PM 25167325
ER
PT J
AU Hughes, DPM
Kummar, S
Lazar, AJ
AF Hughes, Dennis P. M.
Kummar, Shivaani
Lazar, Alexander J.
TI New, Tolerable gamma-Secretase Inhibitor Takes Desmoid Down a Notch
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID ADVANCED SOLID TUMORS; SIGNALING PATHWAY; PHASE-I; CANCER
AB A phase I trial of PF-03084014, an oral reversible gamma-secretase inhibitor, in solid tumor malignancies shows drug tolerability in patients. Evidence of Notch pathway inhibition was demonstrated in peripheral blood. A surprisingly high rate of response was seen in desmoid tumors, a rare but sometimes locally aggressive sarcoma. (C) 2014 AACR.
C1 [Hughes, Dennis P. M.] Univ Texas MD Anderson Canc Ctr, Childrens Canc Hosp, Dept Pediat Res, Houston, TX 77030 USA.
[Kummar, Shivaani] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Lazar, Alexander J.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Lazar, Alexander J.] Univ Texas MD Anderson Canc Ctr, Sarcoma Res Ctr, Houston, TX 77030 USA.
RP Lazar, AJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd,Unit 85, Houston, TX 77030 USA.
EM alazar@mdanderson.org
RI Lazar, Alexander/A-3416-2008
OI Lazar, Alexander/0000-0002-6395-4499
FU NCI NIH HHS [R01 CA141208, P30 CA016672, R01 CA149501, R01CA141208,
R01CA149501]
NR 11
TC 4
Z9 4
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2015
VL 21
IS 1
BP 7
EP 9
DI 10.1158/1078-0432.CCR-14-1660
PG 3
WC Oncology
SC Oncology
GA AY3CQ
UT WOS:000347462600003
PM 25336699
ER
PT J
AU Srinivasan, R
Ricketts, CJ
Sourbier, C
Linehan, WM
AF Srinivasan, Ramaprasad
Ricketts, Christopher J.
Sourbier, Carole
Linehan, W. Marston
TI New Strategies in Renal Cell Carcinoma: Targeting the Genetic and
Metabolic Basis of Disease
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HYPOXIA-INDUCIBLE FACTOR; KIDNEY CANCER; FUMARATE-HYDRATASE; HEREDITARY
LEIOMYOMATOSIS; REDUCTIVE CARBOXYLATION; MET PROTOONCOGENE;
POOR-PROGNOSIS; FACTOR 1-ALPHA; HIF-ALPHA; MUTATIONS
AB The development of new forms of treatment of advanced renal cell carcinoma over the past two decades has been primarily focused on targeting the VHL/HIF pathway. The recent identification of mutations of chromatin-remodeling genes in clear-cell renal carcinoma (ccRCC), of genomic heterogeneity, and of a Warburg-like metabolic phenotype in advanced disease has had a profound effect on our understanding of the evolution of ccRCC and on potential approaches to personalized therapy. Early approaches to therapy for patients with advanced type I papillary RCC that have centered around the MET/HGF pathway will expand as more genomic information becomes available. Sporadic and familial type II papillary renal cell carcinoma are characterized by enhanced aerobic glycolysis and share an antioxidant response phenotype. In fumarate hydratase-deficient RCC, fumarate-induced succination of KEAP1 activates Nrf2 signaling. CUL3 and Nrf2 mutations as well as an Nrf2 activation phenotype are found in sporadic type II papillary RCC. Therapeutic approaches designed to target the Nrf2 pathway as well as to impair blood flow and glucose delivery in these cancers that are highly dependent on a robust tumor vasculature and on ready availability of glucose for energy production and glycolysis are in development. (C) 2015 AACR.
C1 [Srinivasan, Ramaprasad; Ricketts, Christopher J.; Sourbier, Carole; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr MSC 1107,CRC Room 1W-5940, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU NCI NIH HHS [Z01 BC011028-01, Z01 BC011038-01]
NR 74
TC 20
Z9 20
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2015
VL 21
IS 1
BP 10
EP 17
DI 10.1158/1078-0432.CCR-13-2993
PG 8
WC Oncology
SC Oncology
GA AY3CQ
UT WOS:000347462600004
PM 25564569
ER
PT J
AU Reiss, KA
Herman, JM
Zahurak, M
Brade, A
Dawson, LA
Scardina, A
Joffe, C
Petito, E
Hacker-Prietz, A
Kinders, RJ
Wang, LH
Chen, A
Temkin, S
Horiba, N
Siu, LL
Azad, NS
AF Reiss, Kim A.
Herman, Joseph M.
Zahurak, Marianna
Brade, Anthony
Dawson, Laura A.
Scardina, Angela
Joffe, Caitlin
Petito, Emily
Hacker-Prietz, Amy
Kinders, Robert J.
Wang, Lihua
Chen, Alice
Temkin, Sarah
Horiba, Naomi
Siu, Lillian L.
Azad, Nilofer S.
TI A Phase I Study of Veliparib (ABT-888) in Combination with Low-Dose
Fractionated Whole Abdominal Radiation Therapy in Patients with Advanced
Solid Malignancies and Peritoneal Carcinomatosis
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; PARP INHIBITOR; OVARIAN-CANCER;
COLORECTAL ORIGIN; TREATMENT OPTIONS; TUMORS; RADIOTHERAPY; IRINOTECAN;
MODELS; RADIOSENSITIZATION
AB Purpose: The combination of low-dose radiotherapy with PARP inhibition has been shown to enhance antitumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888), a small-molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumor malignancies.
Experimental Design: Patients were treated with veliparib (80320 mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1-3of each cycle. Circulating tumor cells (CTC) were collected and evaluated for gamma-H2AX. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire.
Results: Twenty-two patients were treated. Treatment-related grade 3 and 4 toxicities included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%), and dyspnea (4%). No objective responses were observed. Disease stabilization (>= 24 weeks) was observed in 7 patients (33%). Median progressionfree survival (mPFS) was 4.47 months and median overall survival (mOS) was 13.04 months. In the subset of 8 ovarian and fallopian cancers, mPFS was 6.77 months and mOS was 17.54 months compared with mPFS 2.71 months and mOS 13.01 months in others. Patients with ovarian and fallopian cancers had better QoL over time than those with other cancers. An increased percentage of gamma-H2AX-positive CTCs was observed in a subset of patients (3/6 with > 2 CTCs at baseline).
Conclusions: Combined veliparib and LDFWAR is a welltolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the ovarian and fallopian cancer subpopulation.
C1 [Reiss, Kim A.; Scardina, Angela; Joffe, Caitlin; Petito, Emily; Azad, Nilofer S.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Dept Med Oncol, Baltimore, MD 21287 USA.
[Herman, Joseph M.; Hacker-Prietz, Amy] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Dept Radiat Oncol, Baltimore, MD 21287 USA.
[Zahurak, Marianna] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Stat, Baltimore, MD USA.
[Brade, Anthony; Dawson, Laura A.] Univ Toronto, Univ Hlth Network, Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON M5S 1A1, Canada.
[Kinders, Robert J.; Wang, Lihua] NCI, Off Director, Bethesda, MD 20892 USA.
[Chen, Alice] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Temkin, Sarah; Horiba, Naomi] Univ Maryland, Sch Med, Dept Obstet Gynecol & Reprod Sci, Baltimore, MD 21201 USA.
[Siu, Lillian L.] Univ Toronto, Dept Med Oncol & Hematol, Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5S 1A1, Canada.
RP Azad, NS (reprint author), Johns Hopkins Univ, Sch Med, 1650 Orleans St,Suite 4M10, Baltimore, MD 21287 USA.
EM nazad2@jhmi.edu
FU Princess Margaret Phase I Consortium [U01-CA-132123]; Cancer Center
support grant [P30 UMGCC]; Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins [UO1CA070095]
FX This study was supported by the following grants: U01-CA-132123
(Princess Margaret Phase I Consortium), the P30 UMGCC Cancer Center
support grant, and the Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins, grant UO1CA070095.
NR 47
TC 19
Z9 21
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JAN 1
PY 2015
VL 21
IS 1
BP 68
EP 76
DI 10.1158/1078-0432.CCR-14-1552
PG 9
WC Oncology
SC Oncology
GA AY3CQ
UT WOS:000347462600011
PM 25355929
ER
PT J
AU Baranello, RJ
Bharani, KL
Padmaraju, V
Chopra, N
Lahiri, DK
Greig, NH
Pappolla, MA
Sambamurti, K
AF Baranello, Robert J.
Bharani, Krishna L.
Padmaraju, Vasudevaraju
Chopra, Nipun
Lahiri, Debomoy K.
Greig, Nigel H.
Pappolla, Miguel A.
Sambamurti, Kumar
TI Amyloid-Beta Protein Clearance and Degradation (ABCD) Pathways and their
Role in Alzheimer's Disease
SO CURRENT ALZHEIMER RESEARCH
LA English
DT Article
DE Alzheimer's disease; amyloid beta degradation; amyloid beta peptide;
endothelin-converting enzyme; insulin-degrading enzyme; neprilysin;
neurodegeneration
ID INSULIN-DEGRADING ENZYME; ANGIOTENSIN-CONVERTING ENZYME;
RECEPTOR-RELATED PROTEIN; UBIQUITIN-PROTEASOME PATHWAY; N-END RULE;
PRECURSOR PROTEIN; A-BETA; APOLIPOPROTEIN-E; MATRIX METALLOPROTEINASES;
GAMMA-SECRETASE
AB Amyloid-beta proteins (A beta) of 42 (A beta 42) and 40 aa (A beta 40) accumulate as senile plaques (SP) and cerebrovascular amyloid protein deposits that are defining diagnostic features of Alzheimer's disease (AD). A number of rare mutations linked to familial AD (FAD) on the A beta precursor protein (APP), Presenilin-1 (PS1), Presenilin-2 (PS2), Adamalysin10, and other genetic risk factors for sporadic AD such as the epsilon 4 allele of Apolipoprotein E (ApoE-epsilon 4) foster the accumulation of A beta and also induce the entire spectrum of pathology associated with the disease. A beta accumulation is therefore a key pathological event and a prime target for the prevention and treatment of AD. APP is sequentially processed by beta-site APP cleaving enzyme (BACE1) and gamma-secretase, a multisubunit PS1/PS2-containing integral membrane protease, to generate A beta. Although A beta accumulates in all forms of AD, the only pathways known to be affected in FAD increase A beta production by APP gene duplication or via base substitutions on APP and gamma-secretase subunits PS1 and PS2 that either specifically increase the yield of the longer A beta 42 or both A beta 40 and A beta 42. However, the vast majority of AD patients accumulate A beta without these known mutations. This led to proposals that impairment of A beta degradation or clearance may play a key role in AD pathogenesis. Several candidate enzymes, including Insulin-degrading enzyme (IDE), Neprilysin (NEP), Endothelin-converting enzyme (ECE), Angiotensin converting enzyme (ACE), Plasmin, and Matrix metalloproteinases (MMPs) have been identified and some have even been successfully evaluated in animal models. Several studies also have demonstrated the capacity of gamma-secretase inhibitors to paradoxically increase the yield of A beta and we have recently established that the mechanism is by skirting A beta degradation. This review outlines major cellular pathways of A beta degradation to provide a basis for future efforts to fully characterize the panel of pathways responsible for A beta turnover.
C1 [Baranello, Robert J.; Bharani, Krishna L.; Padmaraju, Vasudevaraju; Sambamurti, Kumar] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Chopra, Nipun; Lahiri, Debomoy K.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Greig, Nigel H.] NIA, Drug Design & Dev Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Pappolla, Miguel A.] Univ Texas Med Branch, Dept Neurol, Galveston, TX 77555 USA.
RP Sambamurti, K (reprint author), Med Univ S Carolina, Dept Neurosci, 173 Ashley Ave,BSB 403, Charleston, SC 29425 USA.
EM sambak@musc.edu
RI Bharani, Krishna/D-4179-2016
OI Bharani, Krishna/0000-0002-5441-4423
FU Alzheimer Association IIRG [10-173-180]; Alzheimer Association NIH
[AG046200, AG042804]; Alzheimer's Association [IIRG-11-206418]; NIA;
MSTP grant [NIH T32 GM08716-13]
FX The authors thank the Alzheimer's Association IIRG 10-173-180 and NIH
AG046200 to KS, Alzheimer's Association IIRG-11-206418 and NIH AG042804
to DKL and Intramural NIA to NHG supported this work. KLB was supported
by an MSTP grant - NIH T32 GM08716-13. The authors thank Ms. Meera
Parasuraman for reading and editing the manuscript.
NR 196
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U1 3
U2 27
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1567-2050
EI 1875-5828
J9 CURR ALZHEIMER RES
JI Curr. Alzheimer Res.
PY 2015
VL 12
IS 1
BP 32
EP 46
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AY0PS
UT WOS:000347299500004
PM 25523424
ER
PT J
AU El Meskini, R
Iacovelli, AJ
Kulaga, A
Gumprecht, M
Martin, PL
Baran, M
Householder, DB
Van Dyke, T
Ohler, ZW
AF El Meskini, Rajaa
Iacovelli, Anthony J.
Kulaga, Alan
Gumprecht, Michelle
Martin, Philip L.
Baran, Maureen
Householder, Deborah B.
Van Dyke, Terry
Ohler, Zoe Weaver
TI A preclinical orthotopic model for glioblastoma recapitulates key
features of human tumors and demonstrates sensitivity to a combination
of MEK and PI3K pathway inhibitors
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Glioblastoma; Mouse model; PI3K and MEK inhibition; Apoptosis
ID HIGH-GRADE ASTROCYTOMAS; IN-VIVO; MALIGNANT ASTROCYTOMAS;
RADIATION-THERAPY; MOUSE MODELS; BRAIN-TUMORS; PHASE-I; ACTIVATION;
GLIOMAS; PI3K/MTOR
AB Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Previous work describes a genetically engineered mouse (GEM) model that contains perturbations in the most frequently dysregulated networks in GBM (driven by RB, KRAS and/or PI3K signaling and PTEN) that induce development of Grade IV astrocytoma with properties of the human disease. Here, we developed and characterized an orthotopic mouse model derived from the GEM that retains the features of the GEM model in an immunocompetent background; however, this model is also tractable and efficient for preclinical evaluation of candidate therapeutic regimens. Orthotopic brain tumors are highly proliferative, invasive and vascular, and express histology markers characteristic of human GBM. Primary tumor cells were examined for sensitivity to chemotherapeutics and targeted drugs. PI3K and MAPK pathway inhibitors, when used as single agents, inhibited cell proliferation but did not result in significant apoptosis. However, in combination, these inhibitors resulted in a substantial increase in cell death. Moreover, these findings translated into the in vivo orthotopic model: PI3K or MAPK inhibitor treatment regimens resulted in incomplete pathway suppression and feedback loops, whereas dual treatment delayed tumor growth through increased apoptosis and decreased tumor cell proliferation. Analysis of downstream pathway components revealed a cooperative effect on target downregulation. These concordant results, together with the morphologic similarities to the human GBM disease characteristics of the model, validate it as a new platform for the evaluation of GBM treatment.
C1 [El Meskini, Rajaa; Iacovelli, Anthony J.; Kulaga, Alan; Gumprecht, Michelle; Martin, Philip L.; Baran, Maureen; Householder, Deborah B.; Van Dyke, Terry; Ohler, Zoe Weaver] Leidos Biomed Res Inc, Ctr Adv Preclin Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Van Dyke, Terry] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA.
RP Ohler, ZW (reprint author), Leidos Biomed Res Inc, Ctr Adv Preclin Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM zweaverohler@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work has been funded with federal funds from the National Cancer
Institute, National Institutes of Health under Contract No.
HHSN261200800001E.
NR 58
TC 5
Z9 5
U1 0
U2 4
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD JAN
PY 2015
VL 8
IS 1
BP 45
EP 56
DI 10.1242/dmm.018168
PG 12
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA AY1XI
UT WOS:000347382400004
PM 25431423
ER
PT J
AU Attene-Ramos, MS
Huang, RL
Michael, S
Witt, KL
Richard, A
Tice, RR
Simeonov, A
Austin, CP
Xia, MH
AF Attene-Ramos, Matias S.
Huang, Ruili
Michael, Sam
Witt, Kristine L.
Richard, Ann
Tice, Raymond R.
Simeonov, Anton
Austin, Christopher P.
Xia, Menghang
TI Profiling of the Tox21 Chemical Collection for Mitochondrial Function to
Identify Compounds that Acutely Decrease Mitochondrial Membrane
Potential
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID CYTOCHROME-C RELEASE; OXIDATIVE-PHOSPHORYLATION; ENVIRONMENTAL
CHEMICALS; LEUKEMIA-CELLS; DYSFUNCTION; MECHANISM; TOXICITY; APOPTOSIS;
BRYOSTATIN-1; CYTOTOXICITY
AB BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases.
OBJECTIVES: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (similar to 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells.
RESULTS: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cyto-toxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay <= 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP.
CONCLUSIONS: Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity.
C1 [Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Simeonov, Anton; Austin, Christopher P.; Xia, Menghang] NIH, Natl Ctr Advancing Translat Sci, US Dept HHS, Bethesda, MD 20892 USA.
[Witt, Kristine L.; Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Richard, Ann] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
RP Xia, MH (reprint author), NIH, Natl Ctr Advancing Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM mxia@mail.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS)/Division of
the National Toxicology Program [IAG Y2-ES-7020-01]
FX This work was supported through interagency agreement IAG Y2-ES-7020-01
from the National Institute of Environmental Health Sciences
(NIEHS)/Division of the National Toxicology Program to the National
Center for Advancing Translational Sciences, NIH.
NR 45
TC 13
Z9 13
U1 5
U2 21
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 JAN
PY 2015
VL 123
IS 1
BP 49
EP 56
DI 10.1289/ehp.1408642
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AY1YF
UT WOS:000347385000013
PM 25302578
ER
PT J
AU Louis, GMB
Chen, Z
Schisterman, EF
Kim, S
Sweeney, AM
Sundaram, R
Lynch, CD
Gore-Langton, RE
Barr, DB
AF Louis, Germaine M. Buck
Chen, Zhen
Schisterman, Enrique F.
Kim, Sungduk
Sweeney, Anne M.
Sundaram, Rajeshwari
Lynch, Courtney D.
Gore-Langton, Robert E.
Barr, Dana Boyd
TI Perfluorochemicals and Human Semen Quality: The LIFE Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID MALE REPRODUCTIVE HEALTH; SPERM DNA FRAGMENTATION; IN-VITRO;
PERFLUORINATED COMPOUNDS; ENDOCRINE DISRUPTERS; SERUM COTININE;
EXPOSURE; MEN; PERFLUOROOCTANOATE; PFOS
AB BACKGROUND: The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. Objectives: We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy.
METHODS: Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluoro-sulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log-transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points.
RESULTS: Six PFCs [2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluoro-decanoate (PFDeA), perfluoro-nonanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluoro-octane sulfonate (PFOS), and perfluoro-octanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails.
CONCLUSIONS: Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions.
C1 [Louis, Germaine M. Buck; Chen, Zhen; Schisterman, Enrique F.; Kim, Sungduk; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, US Dept HHS, Rockville, MD 20852 USA.
[Sweeney, Anne M.] Univ Texas Rural Sch Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA.
[Lynch, Courtney D.] Ohio State Univ, Dept Obstet & Gynecol, Coll Med, Columbus, OH 43210 USA.
[Gore-Langton, Robert E.] EMMES Corp, Rockville, MD USA.
[Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 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 Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358]
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(N01-HD-3-3355, N01-HD-3-3356, and NOH-HD-3-3358).
NR 68
TC 10
Z9 13
U1 4
U2 32
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 JAN
PY 2015
VL 123
IS 1
BP 57
EP 63
DI 10.1289/ehp.1307621
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AY1YF
UT WOS:000347385000014
PM 25127343
ER
PT J
AU Whirledge, S
Senbanjo, LT
Cidlowski, JA
AF Whirledge, Shannon
Senbanjo, Linda T.
Cidlowski, John A.
TI Genistein Disrupts Glucocorticoid Receptor Signaling in Human Uterine
Endometrial Ishikawa Cells
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID GENE-EXPRESSION; ESTROGEN; DISEASE; BINDING; BETA; SOY; ISOFLAVONES;
INFERTILITY; INVITRO; CANCER
AB BACKGROUND: The link between environmental estrogen exposure and defects in the female reproductive tract is well established. The phytoestrogen genistein is able to modulate uterine estrogen receptor (ER) activity, and dietary exposure is associated with uterine pathologies. Regulation of stress and immune functions by the glucocorticoid receptor (GR) is also an integral part of maintaining reproductive tract function; disruption of GR signaling by genistein may also have a role in the adverse effects of genistein.
OBJECTIVE: We evaluated the transcriptional response to genistein in Ishikawa cells and investigated the effects of genistein on GR-mediated target genes.
METHODS: We used Ishikawa cells as a model system to identify novel targets of genistein and the synthetic gluco-corticoid dexamethasone through whole genome microarray analysis. Common gene targets were defined and response patterns verified by quantitative real-time reverse-transcription polymerase chain reaction. The mechanism of transcriptional antagonism was determined for select genes.
RESULTS: Genistein regulated numerous genes in Ishikawa cells independently of estradiol, and the response to coadministration of genistein and dexamethasone was unique compared with the response to either estradiol or dexamethasone alone. Furthermore, genistein altered gluco-corticoid regulation of GR target genes. In a select set of genes, co-regulation by dexamethasone and genistein was found to require both GR and ER alpha signaling, respectively.
CONCLUSIONS: Using Ishikawa cells, we observed that exposure to genistein resulted in distinct changes in gene expression and unique differences in the GR transcriptome.
C1 [Whirledge, Shannon; Senbanjo, Linda T.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, NIH, MD F3-07,POB 12233, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU Intramural Research Program of the NIEHS, NIH
FX This research was supported by the Intramural Research Program of the
NIEHS, NIH.
NR 34
TC 3
Z9 3
U1 1
U2 7
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 JAN
PY 2015
VL 123
IS 1
BP 80
EP 87
DI 10.1289/ehp.1408437
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AY1YF
UT WOS:000347385000017
PM 25136773
ER
PT J
AU Robledo, CA
Yeung, E
Mendola, P
Sundaram, R
Maisog, J
Sweeney, AM
Barr, DB
Louis, GMB
AF Robledo, Candace A.
Yeung, Edwina
Mendola, Pauline
Sundaram, Rajeshwari
Maisog, Jose
Sweeney, Anne M.
Barr, Dana Boyd
Louis, Germaine M. Buck
TI Preconception Maternal and Paternal Exposure to Persistent Organic
Pollutants and Birth Size: The LIFE Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID POLYBROMINATED DIPHENYL ETHERS; UMBILICAL-CORD BLOOD; SOLID-PHASE
EXTRACTION; POLYCHLORINATED-BIPHENYLS; GESTATIONAL-AGE; DEVELOPMENTAL
TOXICITY; HUMAN-SERUM; PRENATAL EXPOSURE; PREGNANT-WOMEN; FETAL-GROWTH
AB BACKGROUND: Persistent organic pollutants (POPs) are developmental toxicants, but the impact of both maternal and paternal exposures on offspring birth size is largely unexplored.
OBJECTIVE: We examined associations between maternal and paternal serum concentrations of 63 POPs, comprising five major classes of pollutants, with birth size measures.
METHODS: Parental serum concentrations of 9 organo-chlorine pesticides, 1 polybrominated biphenyl (PBB), 7 perfluoroalkyl chemicals (PFCs), 10 polybrominated diphenyl ethers (PBDEs), and 36 polychlorinated biphenyls (PCBs) were measured before conception for 234 couples. Differences in birth weight, length, head circumference, and ponderal index were estimated using multiple linear regression per 1-SD increase in natural log-transformed (ln-transformed) chemicals. Models were estimated separately for each parent and adjusted for maternal age, maternal pre-pregnancy body mass index (kilograms per meter squared) and other confounders, and all models included an interaction term between infant sex and each chemical.
RESULTS: Among girls (n = 117), birth weight was significantly lower (range, 84-195 g) in association with a 1-SD increase in ln-transformed maternal serum concentrations of DDT, PBDE congeners 28 and 183, and paternal serum concentrations of PBDE-183 and PCB-167. Among boys (n = 113), maternal (PCBs 138, 153, 167, 170, 195, and 209 and perfluorooctane sulfonamide) and paternal (PCBs 172 and 195) serum concentrations of several POPs were statistically associated with lower birth weight (range, 98-170 g), whereas paternal concentrations of PBDEs (66, 99) were associated with higher birth weight. Differences in offspring head circumference, length, and ponderal index were also associated with parental exposures.
CONCLUSIONS: Preconceptional maternal and paternal concentrations of several POPs were associated with statistically significant differences in birth size among offspring.
C1 [Robledo, Candace A.; Yeung, Edwina; Mendola, Pauline; Sundaram, Rajeshwari; Maisog, Jose; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD USA.
[Sweeney, Anne M.] Texas A&M Hlth Sci Ctr, Sch Rural Publ Hlth, Dept Epidemiol & Biostat, College Stn, TX USA.
[Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Robledo, CA (reprint author), Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Dept Behav & Community Hlth, 3500 Camp Bowie,EAD 709H, Ft Worth, TX 76107 USA.
EM candace.robledo@unthsc.edu
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Mendola, Pauline/0000-0001-5330-2844;
Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis,
Germaine/0000-0002-1774-4490
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) [N01-HD-3-3355,
N01-HD-3-3356, NOH-HD-3-3358]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD; contracts N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358). The CDC
staff performed the analytic chemistry work for this study under a
Memorandum of Understanding with the NICHD.
NR 61
TC 12
Z9 12
U1 2
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 JAN
PY 2015
VL 123
IS 1
BP 88
EP 94
DI 10.1289/ehp.1308016
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA AY1YF
UT WOS:000347385000018
PM 25095280
ER
PT J
AU Rodriguez-Contreras, D
Aslan, H
Feng, XH
Tran, K
Yates, PA
Kamhawi, S
Landfear, SM
AF Rodriguez-Contreras, Dayana
Aslan, Hamide
Feng, Xiuhong
Tran, Khoa
Yates, Phillip A.
Kamhawi, Shaden
Landfear, Scott M.
TI Regulation and biological function of a flagellar glucose transporter in
Leishmania mexicana: a potential glucose sensor
SO FASEB JOURNAL
LA English
DT Article
DE environmental sensing; Leishmania parasites; protein expression;
transceptor; TaV2A peptide
ID NUCLEOSIDE TRANSPORTER; TRYPANOSOMA-CRUZI; PRIMARY CILIUM; EXPRESSION;
SEQUENCE; NUTRIENT; PROTEIN; HEXOSE; GENE; PROMASTIGOTES
AB In Leishmania mexicana parasites, a unique glucose transporter, LmxGT1, is selectively targeted to the flagellar membrane, suggesting a possible sensory role that is often associated with ciliary membrane proteins. Expression of LmxGT1 is down-regulated similar to 20-fold by increasing cell density but is up-regulated similar to 50-fold by depleting glucose from the medium, and the permease is strongly down-regulated when flagellated insect-stage promastigotes invade mammalian macrophages and transform into intracellular amastigotes. Regulation of LmxGT1 expression by glucose and during the lifecycle operates at the level of protein stability. Significantly, Delta lmxgt1 null mutant, grown in abundant glucose, undergoes catastrophic loss of viability when parasites deplete glucose from the medium, a property not exhibited by wild-type or add-back lines. These results suggest that LmxGT1 may function as a glucose sensor that allows parasites to enter the stationary phase when they deplete glucose and that in the absence of this sensor, parasites do not maintain viability when they run out of glucose. However, alternate roles for LmxGT1 in monitoring glucose availability are considered. The absence of known sensory receptors with defined ligands and biologic functions in Leishmania and related kinetoplastid parasites underscores the potential significance of these observations.
C1 [Rodriguez-Contreras, Dayana; Feng, Xiuhong; Tran, Khoa; Landfear, Scott M.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA.
[Yates, Phillip A.] Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA.
[Aslan, Hamide; Kamhawi, Shaden] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Landfear, SM (reprint author), Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM landfear@ohsu.edu
FU Intramural NIH HHS; NCRR NIH HHS [S10 RR023432, S10-RR023432]; NIAID NIH
HHS [AI023682, AI25920, F32 AI096854, R01 AI023682, R01 AI025920, R37
AI023682]
NR 49
TC 6
Z9 6
U1 0
U2 9
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 JAN
PY 2015
VL 29
IS 1
BP 11
EP 24
DI 10.1096/fj.14-251991
PG 14
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA AY1UX
UT WOS:000347378600003
PM 25300620
ER
PT J
AU Csoka, B
Nemeth, ZH
Toro, G
Koscso, B
Kokai, E
Robson, SC
Enjyoji, K
Rolandelli, RH
Erdelyi, K
Pacher, P
Hasko, G
AF Csoka, Balazs
Nemeth, Zoltan H.
Toero, Gabor
Koscso, Balazs
Kokai, Endre
Robson, Simon C.
Enjyoji, Keiichi
Rolandelli, Rolando H.
Erdelyi, Katalin
Pacher, Pal
Hasko, Gyoergy
TI CD39 improves survival in microbial sepsis by attenuating systemic
inflammation
SO FASEB JOURNAL
LA English
DT Article
DE interleukin; TNF; MIP; lung; kidney
ID ISCHEMIA-REPERFUSION INJURY; A(2B) ADENOSINE RECEPTORS; MURINE SEPTIC
PERITONITIS; ECTO-5'-NUCLEOTIDASE CD73; POLYMICROBIAL SEPSIS;
TRIPHOSPHATE DIPHOSPHOHYDROLASE-1; DECREASES MORTALITY; HEPATIC-INJURY;
MACROPHAGES; DYSFUNCTION
AB Sepsis remains the leading cause of morbidity and mortality in critically ill patients. Excessive inflammation is a major cause of organ failure and mortality in sepsis. Ectonucleoside triphosphate diphosphohydrolase 1, ENTPDase1 (CD39) is a cell surface nucleotide-metabolizing enzyme, which degrades the extracellular purines ATP and ADP, thereby regulating purinergic receptor signaling. Although the role of purinergic receptor signaling in regulating inflammation and sepsis has been addressed previously, the role of CD39 in regulating the host's response to sepsis is unknown. We found that the CD39 mimic apyrase (250 U/kg) decreased and knockout or pharmacologic blockade with sodium polyoxotungstate (5 mg/kg; IC50 approximate to 10 mu M) of CD39 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture. CD39 decreased inflammation, organ damage, immune cell apoptosis, and bacterial load. Use of bone marrow chimeric mice revealed that CD39 expression on myeloid cells decreases inflammation in septic mice. CD39 expression is upregulated during sepsis in mice, as well as in both murine and human macrophages stimulated with Escherichia coli. Moreover, E. coli increases CD39 promoter activity in macrophages. Altogether, these data indicate CD39 as an evolutionarily conserved inducible protective pathway during sepsis. We propose CD39 as a novel therapeutic target in the management of sepsis.
C1 [Csoka, Balazs; Nemeth, Zoltan H.; Koscso, Balazs; Hasko, Gyoergy] Rutgers New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Csoka, Balazs; Koscso, Balazs; Hasko, Gyoergy] Rutgers New Jersey Med Sch, Ctr Immun & Inflammat, Newark, NJ 07103 USA.
[Nemeth, Zoltan H.; Rolandelli, Rolando H.] Morristown Med Ctr, Dept Surg, Morristown, NJ USA.
[Toero, Gabor; Kokai, Endre; Hasko, Gyoergy] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, H-4012 Debrecen, Hungary.
[Robson, Simon C.; Enjyoji, Keiichi] Beth Israel Deaconess Med Ctr, Dept Med, Gastroenterol & Transplant Inst, Boston, MA 02215 USA.
[Robson, Simon C.; Enjyoji, Keiichi] Harvard Univ, Sch Med, Boston, MA USA.
[Erdelyi, Katalin; Pacher, Pal] NIAAA, Bethesda, MD USA.
RP Hasko, G (reprint author), Rutgers New Jersey Med Sch, Dept Surg, 185 South Orange Ave, Newark, NJ 07103 USA.
EM haskoge@njms.rutgers.edu
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Intramural NIH HHS; NIGMS NIH HHS [R01GM66189, R01 GM066189]
NR 55
TC 7
Z9 7
U1 5
U2 12
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 JAN
PY 2015
VL 29
IS 1
BP 25
EP 36
DI 10.1096/fj.14-253567
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA AY1UX
UT WOS:000347378600004
PM 25318479
ER
PT J
AU House, JS
Li, HL
DeGraff, LM
Flake, G
Zeldin, DC
London, SJ
AF House, John S.
Li, Huiling
DeGraff, Laura M.
Flake, Gordon
Zeldin, Darryl C.
London, Stephanie J.
TI Genetic variation in HTR4 and lung function: GWAS follow-up in mouse
SO FASEB JOURNAL
LA English
DT Article
DE pulmonary function; airway hyperresponsiveness; mouse models
ID GENOME-WIDE ASSOCIATION; OBSTRUCTIVE PULMONARY-DISEASE; SEROTONIN 5-HT4
RECEPTORS; AIRWAY HYPERRESPONSIVENESS; ASTHMA; EXPRESSION; KNOCK;
IDENTIFICATION; HIPPOCAMPUS; VARIANTS
AB Human genome-wide association studies (GWASs) have identified numerous associations between single nucleotide polymorphisms (SNPs) and pulmonary function. Proving that there is a causal relationship between GWAS SNPs, many of which are noncoding and without known functional impact, and these traits has been elusive. Furthermore, noncoding GWAS-identified SNPs may exert trans-regulatory effects rather than impact the proximal gene. Noncoding variants in 5-hydroxytryptamine (serotonin) receptor 4 (HTR4) are associated with pulmonary function in human GWASs. To gain insight into whether this association is causal, we tested whether Htr4-null mice have altered pulmonary function. We found that HTR4-deficient mice have 12% higher baseline lung resistance and also increased methacholine-induced airway hyper responsiveness (AHR) as measured by lung resistance (27%), tissue resistance (48%), and tissue elastance (30%). Furthermore, Htr4-null mice were more sensitiveto serotonin-induced AHR. In models of exposure to bacterial lipopolysaccharide, bleomycin, and allergic airway inflammation induced by house dust mites, pulmonary function and cytokine profiles in Htr4-null mice differed little from their wild-type controls. The findings of altered baseline lung function and increased AHR in Htr4-null mice support a causal relationship between genetic variation in HTR4 and pulmonary function identified in human GWAS.
C1 [House, John S.; Li, Huiling; DeGraff, Laura M.; Zeldin, Darryl C.; London, Stephanie J.] NIEHS, Div Intramural Res, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA.
[Flake, Gordon] US Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Res Triangle Pk, NC USA.
RP London, SJ (reprint author), NIEHS, NIH, 111 TW Alexander Dr,POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
OI House, John S./0000-0002-8447-7871; London,
Stephanie/0000-0003-4911-5290
FU Intramural NIH HHS; NIBIB NIH HHS [P41 EB015897]; NIEHS NIH HHS [Z01
ES025045, Z01 ES043012]; PHS HHS [Z01 025043]
NR 54
TC 1
Z9 1
U1 1
U2 6
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 JAN
PY 2015
VL 29
IS 1
BP 323
EP 335
DI 10.1096/fj.14-253898
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA AY1UX
UT WOS:000347378600030
PM 25342126
ER
PT J
AU Markland, A
Wang, L
Jelovsek, JE
Brubaker, L
Tuteja, A
Weidner, AC
LoSavio, A
Corton, M
Meikle, S
Richter, HE
AF Markland, Alayne
Wang, Lu
Jelovsek, J. Eric
Brubaker, Linda
Tuteja, Ashook
Weidner, Alison C.
LoSavio, Andelka
Corton, Marlene
Meikle, Susan
Richter, Holly E.
TI Symptom Improvement in Women After Fecal Incontinence Treatments: A
Multicenter Cohort Study of the Pelvic Floor Disorders Network
SO FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY
LA English
DT Article
DE fecal incontinence; cohort study; surgical treatment; nonsurgical
treatment; quality of life
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; BIOFEEDBACK;
QUESTIONNAIRE; EPIDEMIOLOGY; POPULATION; OUTCOMES; PATIENT; ADULTS
AB Objectives: The study aims were to characterize women with fecal incontinence (FI) and measure changes in FI severity and quality of life 3 and 12 months after treatment.
Methods: This study is a secondary analysis of a multicenter study measuring adaptive behaviors among women with FI. Women included had a primary complaint of at least monthly FI over 3 consecutive months and planned FI treatment. Demographic and medical history data were obtained at baseline. Data were collected at baseline, 3 months, and 12 months after clinically selected, nonstandardized treatment. Validated questionnaires were as follows: Fecal Incontinence Severity Index, Modified Manchester Health Questionnaire, Pelvic Floor Disorders Inventory's Colorectal and Anal Distress Inventory, Pelvic Floor Impact Questionnaire's Colorectal and Anal Impact Questionnaire, and Medical Outcomes Study Short Form. Questionnaire score changes from baseline were compared using paired t tests at 3 and 12 months after treatment.
Results: Of the 133 women enrolled, 90 women had treatment data at 3 months and 77 at 12 months. Nonsurgical therapies were the most common (78%) with anal sphincter repair in 22%. Fecal Incontinence Severity Index scores and Modified Manchester Health Questionnaire scores significantly improved 3 months after nonsurgical and surgical treatments (-8.8 +/- 12.0 and -12.6 +/- 19.2, respectively, P < 0.001), as did Colorectal-Anal Distress Inventory and Colorectal-Anal Impact Questionnaire scores (-52.7 +/- 70.0 and -60.6 +/- 70.0, respectively, P < 0.001) and Medical Outcomes Study Short Form mental health scores (4.2 +/- 9.4, P = 0.001). Improvement persisted 12 months posttreatment.
Conclusions: In women seeking care for FI, symptom severity and condition-specific quality of life significantly improve within the first 3 months after FI treatment and are maintained up to 12 months.
C1 [Markland, Alayne] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
[Wang, Lu] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Jelovsek, J. Eric] Cleveland Clin, Dept Obstet Gynecol, Cleveland, OH 44106 USA.
[Jelovsek, J. Eric] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44106 USA.
[Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol, Chicago, IL USA.
[Tuteja, Ashook] Univ Utah, Salt Lake City Vet Affairs Med Ctr, Dept Med, Salt Lake City, UT USA.
[Weidner, Alison C.] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA.
[LoSavio, Andelka] Loyola Univ Chicago, Stritch Sch Med, Dept Med, Chicago, IL USA.
[Corton, Marlene] Univ Texas Southwestern, Dept Obstet & Gynecol, Dallas, TX USA.
[Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Richter, Holly E.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL USA.
RP Markland, A (reprint author), Birmingham Vet Affairs Med Ctr, Dept Med, Div Gerontol Geriatr & Palliat Care, GRECC 11-G,Room 8220,700 South 19th St, Birmingham, AL 35233 USA.
EM amarkland@uabmc.edu
OI Markland, Alayne/0000-0002-6567-6744
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health Office of Research on Women's
Health [U01 HD41249, U10 HD41250, U10 HD41261, U10 HD41267, U10 HD54136,
U10 HD54214, U10 HD54215, U10 HD54241]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development and the National Institutes of
Health Office of Research on Women's Health (U01 HD41249, U10 HD41250,
U10 HD41261, U10 HD41267, U10 HD54136, U10 HD54214, U10 HD54215, and U10
HD54241).
NR 29
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2151-8378
EI 2154-4212
J9 FEMALE PELVIC MED RE
JI Female Pelvic Med. Reconstr. Surg.
PD JAN-FEB
PY 2015
VL 21
IS 1
BP 46
EP 52
DI 10.1097/SPV.0000000000000099
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AY3DN
UT WOS:000347464800015
PM 25185613
ER
PT J
AU Reinhold, WC
Varma, S
Rajapakse, VN
Luna, A
Sousa, FG
Kohn, KW
Pommier, YG
AF Reinhold, William C.
Varma, Sudhir
Rajapakse, Vinodh N.
Luna, Augustin
Sousa, Fabricio Garmus
Kohn, Kurt W.
Pommier, Yves G.
TI Using drug response data to identify molecular effectors, and molecular
"omic" data to identify candidate drugs in cancer
SO HUMAN GENETICS
LA English
DT Review
ID TUMOR-CELL-LINES; MICRORNA EXPRESSION PROFILES; GENE-EXPRESSION;
VARIABLE SELECTION; MESSENGER-RNA; PANEL; SENSITIVITY; SCREEN;
IDENTIFICATION; MUTATIONS
AB The current convergence of molecular and pharmacological data provides unprecedented opportunities to gain insights into the relationships between the two types of data. Multiple forms of large-scale molecular data, including but not limited to gene and microRNA transcript expression, DNA somatic and germline variations from next-generation DNA and RNA sequencing, and DNA copy number from array comparative genomic hybridization are all potentially informative when one attempts to recognize the panoply of potentially influential events both for cancer progression and therapeutic outcome. Concurrently, there has also been a substantial expansion of the pharmacological data being accrued in a systematic fashion. For cancer cell lines, the National Cancer Institute cell line panel (NCI-60), the Cancer Cell Line Encyclopedia (CCLE), and the collaborative Genomics of Drug Sensitivity in Cancer (GDSC) databases all provide subsets of these forms of data. For the patient-derived data, The Cancer Genome Atlas (TCGA) provides analogous forms of genomic information along with treatment histories. Integration of these data in turn relies on the fields of statistics and statistical learning. Multiple algorithmic approaches may be chosen, depending on the data being considered, and the nature of the question being asked. Combining these algorithms with prior biological knowledge, the results of molecular biological studies, and the consideration of genes as pathways or functional groups provides both the challenge and the potential of the field. The ultimate goal is to provide a paradigm shift in the way that drugs are selected to provide a more targeted and efficacious outcome for the patient.
C1 [Reinhold, William C.; Varma, Sudhir; Rajapakse, Vinodh N.; Luna, Augustin; Sousa, Fabricio Garmus; Kohn, Kurt W.; Pommier, Yves G.] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Varma, Sudhir] HiThru Analyt LLC, Laurel, MD 20707 USA.
[Luna, Augustin] Mem Sloan Kettering Canc Ctr, Comp Biol Program, New York, NY 10021 USA.
[Sousa, Fabricio Garmus] Univ Fed Mato Grosso do Sul, CETROGEN, PPGFARM, BR-79070900 Campo Grande, MS, Brazil.
[Varma, Sudhir] HiThru Analyt LLC, Laurel, MD 20707 USA.
RP Reinhold, WC (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Room 5041, Bethesda, MD 20892 USA.
EM wcr@mail.nih.gov; pommier@nih.gov
RI Sousa, Fabricio/O-8878-2015
OI Sousa, Fabricio/0000-0003-0444-754X
FU Center for Cancer Research, Intramural Program of the National Cancer
Institute [Z01 BC 006150]; MSKCC Genome Data Analysis Center [U24
CA143840]; National Cancer Institute (NCI)/National Human Genome
Research Institute (NHGRI)
FX Our studies are supported by the Center for Cancer Research, Intramural
Program of the National Cancer Institute (Z01 BC 006150). This work was
also supported in part by a MSKCC Genome Data Analysis Center Grant (U24
CA143840) awarded as part of the National Cancer Institute
(NCI)/National Human Genome Research Institute (NHGRI).
NR 71
TC 8
Z9 8
U1 2
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD JAN
PY 2015
VL 134
IS 1
BP 3
EP 11
DI 10.1007/s00439-014-1482-9
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AY0NW
UT WOS:000347294000002
PM 25213708
ER
PT J
AU Davis, JM
Searles, VB
Anderson, N
Keeney, J
Raznahan, A
Horwood, LJ
Fergusson, DM
Kennedy, MA
Giedd, J
Sikela, JM
AF Davis, Jonathon M.
Searles, Veronica B.
Anderson, Nathan
Keeney, Jonathon
Raznahan, Armin
Horwood, L. John
Fergusson, David M.
Kennedy, Martin A.
Giedd, Jay
Sikela, James M.
TI DUF1220 copy number is linearly associated with increased cognitive
function as measured by total IQ and mathematical aptitude scores
SO HUMAN GENETICS
LA English
DT Article
ID GENERAL INTELLIGENCE; CHILDREN; HERITABILITY; EVOLUTION; DOMAINS;
CORTEX; SIZE
AB DUF1220 protein domains exhibit the greatest human lineage-specific copy number expansion of any protein-coding sequence in the genome, and variation in DUF1220 copy number has been linked to both brain size in humans and brain evolution among primates. Given these findings, we examined associations between DUF1220 subtypes CON1 and CON2 and cognitive aptitude. We identified a linear association between CON2 copy number and cognitive function in two independent populations of European descent. In North American males, an increase in CON2 copy number corresponded with an increase in WISC IQ (R (2) = 0.13, p = 0.02), which may be driven by males aged 6-11 (R (2) = 0.42, p = 0.003). We utilized ddPCR in a subset as a confirmatory measurement. This group had 26-33 copies of CON2 with a mean of 29, and each copy increase of CON2 was associated with a 3.3-point increase in WISC IQ (R (2) = 0.22, p = 0.045). In individuals from New Zealand, an increase in CON2 copy number was associated with an increase in math aptitude ability (R (2) = 0.10 p = 0.018). These were not confounded by brain size. To our knowledge, this is the first study to report a replicated association between copy number of a gene coding sequence and cognitive aptitude. Remarkably, dosage variations involving DUF1220 sequences have now been linked to human brain expansion, autism severity and cognitive aptitude, suggesting that such processes may be genetically and mechanistically inter-related. The findings presented here warrant expanded investigations in larger, well-characterized cohorts.
C1 [Davis, Jonathon M.; Searles, Veronica B.; Anderson, Nathan; Keeney, Jonathon; Sikela, James M.] Univ Colorado, Dept Biochem & Mol Genet & Human Med Genet, Med Scientist Training Program, Sch Med, Aurora, CO 80045 USA.
[Davis, Jonathon M.; Searles, Veronica B.; Anderson, Nathan; Keeney, Jonathon; Sikela, James M.] Univ Colorado, Dept Biochem & Mol Genet & Human Med Genet, Med Scientist Neurosci Program, Sch Med, Aurora, CO 80045 USA.
[Raznahan, Armin; Giedd, Jay] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Horwood, L. John; Fergusson, David M.] Univ Otago, Dept Psychol Med, Christchurch Hlth & Dev Study, Christchurch 8140, New Zealand.
[Kennedy, Martin A.] Univ Otago, Dept Pathol, Gene Struct & Funct Lab, Christchurch 8140, New Zealand.
RP Sikela, JM (reprint author), Univ Colorado, Dept Biochem & Mol Genet & Human Med Genet, Med Scientist Training Program, Sch Med, Anschutz Med Campus,RC1-S,L18-10125, Aurora, CO 80045 USA.
EM james.sikela@ucdenver.edu
RI Giedd, Jay/J-9644-2015; Kennedy, Martin/A-4942-2008
OI Giedd, Jay/0000-0003-2002-8978; Kennedy, Martin/0000-0002-6445-8526
FU NIH [R01 MH081203]; Colorado Clinical and Translational Science
Institute [TL1 TR001081]; Coleman Institute for Cognitive Disabilities;
Health Research Council of New Zealand; National Child Health Research
Foundation; Canterbury Medical Research Foundation; New Zealand Lottery
Grants Board; Marsden Fund; James Hume Bequest Fund
FX Funding for this work was provided by NIH R01 MH081203 (JMS), Colorado
Clinical and Translational Science Institute TL1 TR001081 (VBS), and a
Graduate Assistantship from the Coleman Institute for Cognitive
Disabilities (JK). CHDS was funded by Grants from the Health Research
Council of New Zealand, the National Child Health Research Foundation,
the Canterbury Medical Research Foundation, the New Zealand Lottery
Grants Board, the Marsden Fund, and the James Hume Bequest Fund. We
thank Allison Miller for preparation of DNA samples.
NR 29
TC 5
Z9 6
U1 2
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD JAN
PY 2015
VL 134
IS 1
BP 67
EP 75
DI 10.1007/s00439-014-1489-2
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA AY0NW
UT WOS:000347294000008
PM 25287832
ER
PT J
AU Mansoor, A
Patsekin, V
Scherl, D
Robinson, JP
Rajwa, B
AF Mansoor, Awais
Patsekin, Valery
Scherl, Dale
Robinson, J. Paul
Rajwa, Bartlomiej
TI A Statistical Modeling Approach to Computer-Aided Quantification of
Dental Biofilm
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Article
DE Biofilm; dental plaque; Gaussian Markov random field (GMRF);
quantitative fluorescence; superpixelization
ID LIGHT-INDUCED FLUORESCENCE; IMAGE SEGMENTATION; PLAQUE; CLASSIFICATION;
RELIABILITY; VALIDATION; CARIES; QLF
AB Biofilm is a formation of microbial material on tooth substrata. Several methods to quantify dental biofilm coverage have recently been reported in the literature, but at best they provide a semiautomated approach to quantification with significant input from a human grader that comes with the grader's bias of what is foreground, background, biofilm, and tooth. Additionally, human assessment indices limit the resolution of the quantification scale; most commercial scales use five levels of quantification for biofilm coverage (0%, 25%, 50%, 75%, and 100%). On the other hand, current state-of-the-art techniques in automatic plaque quantification fail to make their way into practical applications owing to their inability to incorporate human input to handle misclassifications. This paper proposes a new interactive method for biofilm quantification in Quantitative light-induced fluorescence (QLF) images of canine teeth that is independent of the perceptual bias of the grader. The method partitions a QLF image into segments of uniform texture and intensity called superpixels; every superpixel is statistically modeled as a realization of a single 2-D Gaussian Markov random field (GMRF) whose parameters are estimated; the superpixel is then assigned to one of three classes (background, biofilm, tooth substratum) based on the training set of data. The quantification results show a high degree of consistency and precision. At the same time, the proposed method gives pathologists full control to postprocess the automatic quantification by flipping misclassified superpixels to a different state (background, tooth, biofilm) with a single click, providing greater usability than simply marking the boundaries of biofilm and tooth as done by current state-of-the-art methods.
C1 [Mansoor, Awais] Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47906 USA.
[Mansoor, Awais] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Patsekin, Valery; Rajwa, Bartlomiej] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47906 USA.
[Robinson, J. Paul] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47906 USA.
[Scherl, Dale] Hills Pet Nutr, Topeka, KS 66603 USA.
RP Mansoor, A (reprint author), Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47906 USA.
EM awais.mansoor@gmail.com; vpatseki@purdue.edu; DaleScherl@hillpet.com;
wombat@purdue.edu; brajwa@purdue.edu
RI Rajwa, Bartek/B-3169-2009
OI Rajwa, Bartek/0000-0001-7540-8236
NR 39
TC 1
Z9 1
U1 0
U2 8
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD JAN
PY 2015
VL 19
IS 1
BP 358
EP 366
DI 10.1109/JBHI.2014.2310204
PG 9
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA AY1GP
UT WOS:000347342300043
PM 25710065
ER
PT J
AU Williamson, JD
Launer, LJ
Miller, ME
AF Williamson, Jeff D.
Launer, Lenore J.
Miller, Michael E.
CA ACCORD MIND Investigators
TI Faster Brain Shrinkage in the ACCORD MIND Study: An Unexpected Result?
Reply
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
C1 [Williamson, Jeff D.] Wake Forest Univ, Dept Internal Med, Roena B Kulynych Ctr Memory & Cognit Res, Winston Salem, NC 27109 USA.
[Launer, Lenore J.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Miller, Michael E.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
RP Williamson, JD (reprint author), Wake Forest Sch Med, Dept Internal Med, Roena B Kulynych Ctr Memory & Cognit Res, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM jwilliam@wakehealth.edu
NR 1
TC 0
Z9 0
U1 1
U2 2
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 JAN
PY 2015
VL 175
IS 1
BP 144
EP 145
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA AY1BM
UT WOS:000347328500040
PM 25560951
ER
PT J
AU Williams, PL
Crain, MJ
Yildirim, C
Hazra, R
Van Dyke, RB
Rich, K
Read, JS
Stuard, E
Rathore, M
Mendez, HA
Watts, DH
AF Williams, Paige L.
Crain, Marilyn J.
Yildirim, Cenk
Hazra, Rohan
Van Dyke, Russell B.
Rich, Kenneth
Read, Jennifer S.
Stuard, Emma
Rathore, Mobeen
Mendez, Hermann A.
Watts, D. Heather
CA Pediat HIV AIDS Cohort Study
TI Congenital Anomalies and In Utero Antiretroviral Exposure in Human
Immunodeficiency Virus-Exposed Uninfected Infants
SO JAMA PEDIATRICS
LA English
DT Article
ID HIV-INFECTED WOMEN; BIRTH-DEFECTS; 1ST TRIMESTER; PREGNANCY; RISK;
THERAPY; CHILDREN; SAFETY; BORN; ABNORMALITIES
AB IMPORTANCE Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)-infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.
OBJECTIVE To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.
DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.
EXPOSURES First-trimester exposure to any ARV and to specific ARV medications.
MAIN OUTCOMES AND MEASURES The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.
RESULTS Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78%(95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.
CONCLUSIONS AND RELEVANCE Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.
C1 [Williams, Paige L.; Yildirim, Cenk] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Crain, Marilyn J.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Van Dyke, Russell B.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA.
[Rich, Kenneth] Univ Illinois, Dept Pediat, Chicago, IL USA.
[Read, Jennifer S.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Stuard, Emma] Bronx Lebanon Hosp Ctr, Dept Pediat Infect Dis, Bronx, NY USA.
[Rathore, Mobeen] Univ Florida, Ctr HIV AIDS Res Educ & Serv, Jacksonville, FL USA.
[Mendez, Hermann A.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Watts, D. Heather] US Dept State, Off US Global AIDS Coordinator, Washington, DC 20520 USA.
RP Williams, PL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA.
EM paige@sdac.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute on Drug Abuse
FX The study was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, with co-funding from the National
Institute on Drug Abuse, the National Institute of Allergy and
Infectious Diseases, the Office of AIDS Research, the National Institute
of Mental Health, the National Institute of Neurological Disorders and
Stroke, the National Institute on Deafness and Other Communication
Disorders, the National Heart, Lung, and Blood Institute, the National
Institute of Dental and Craniofacial Research, and the National
Institute on Alcohol Abuse and Alcoholism, through cooperative
agreements with the Harvard School of Public Health (HD052102, 3 U01
HD052102-05S1, and 3 U01 HD052102-06S3) (principal investigator George
Seage and project director Julie Alperen) and the Tulane University
School of Medicine (HD052104 and 3U01HD052104-06S1) (principal
investigator Russell B. Van Dyke, coprincipal investigator Kenneth Rich,
and project director Patrick Davis). Data management services were
provided by the Frontier Science and Technology Research Foundation, Inc
(principal investigator Suzanne Siminski), and regulatory services and
logistical support were provided byWestat, Inc (principal investigator
Julie Davidson).
NR 32
TC 11
Z9 11
U1 1
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JAN
PY 2015
VL 169
IS 1
BP 48
EP 55
DI 10.1001/jamapediatrics.2014.1889
PG 8
WC Pediatrics
SC Pediatrics
GA AY1JI
UT WOS:000347349300014
PM 25383770
ER
PT J
AU McGowan, EC
Bloomberg, GR
Gergen, PJ
Visness, CM
Jaffee, KF
Sandel, M
O'Connor, G
Kattan, M
Gern, J
Wood, RA
AF McGowan, Emily C.
Bloomberg, Gordon R.
Gergen, Peter J.
Visness, Cynthia M.
Jaffee, Katy F.
Sandel, Megan
O'Connor, George
Kattan, Meyer
Gern, James
Wood, Robert A.
TI Influence of early-life exposures on food sensitization and food allergy
in an inner-city birth cohort
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Food allergy; inner city; Urban Environment and Childhood Asthma cohort;
specific IgE
ID PEANUT-SPECIFIC IGG; EGG ALLERGY; NATIONAL-HEALTH; EARLY-CHILDHOOD;
UNITED-STATES; PREVALENCE; CHILDREN; ASTHMA; ENDOTOXIN; URBAN
AB Objective: Previous data suggest that food allergy (FA) might be more common in inner-city children; however, these studies have not collected data on both sensitization and clinical reactivity or early-life exposures.
Methods: Children in the Urban Environment and Childhood Asthma birth cohort were followed through age 5 years. Household exposures, diet, clinical history, and physical examinations were assessed yearly; levels of specific IgE to milk, egg, and peanut were measured at 1, 2, 3, and 5 years of age. On the basis of sensitization (IgE >= 0.35 kU/L) and clinical history over the 5-year period, children were classified as having FA or being possibly allergic, sensitized but tolerant, or not allergic/not sensitized.
Results: Five hundred sixteen children were included. Overall, 55.4% were sensitized (milk, 46.7%; egg, 31.0%; and peanut, 20.9%), whereas 9.9% were categorized as having FA (peanut, 6.0%; egg, 4.3%; andmilk, 2.7%; 2.5% to > 1 food). The remaining children were categorized as possibly allergic (17.0%), sensitized but tolerant (28.5%), and not sensitized (44.6%). Eighteen (3.5%) reported reactions to foods forwhich IgElevelswere not measured. Food-specific IgE levels were similar in children with FA versus sensitized but tolerant children, except for egg, levels ofwhich were higher in patients with FA at ages 1 and 2 years. FA was associated with recurrent wheeze, eczema, aeroallergen sensitization, male sex, breast-feeding, and lower endotoxin exposure in year 1 but not with race/ethnicity, income, tobacco exposure, maternal stress, or early introduction of solid foods.
Conclusions: Even given that this was designed to be a high-risk cohort, the cumulative incidence of FA is extremely high, especially considering the strict definition of FA that was applied and that only 3 common allergens were included.
C1 [McGowan, Emily C.] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Dept Med, Baltimore, MD 21287 USA.
[McGowan, Emily C.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Bloomberg, Gordon R.] Washington Univ, Sch Med, Div Allergy Immunol & Pulm Med, St Louis, MO 63130 USA.
[Gergen, Peter J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Visness, Cynthia M.; Jaffee, Katy F.] Rho Inc, Chapel Hill, NC USA.
[Sandel, Megan] Boston Univ, Sch Med, Dept Med, Div Pediat Primary Care, Boston, MA 02118 USA.
[O'Connor, George] Boston Univ, Sch Med, Dept Med, Div Pulm Allergy Sleep & Crit Care Med, Boston, MA 02118 USA.
[Kattan, Meyer] New York Presbyterian Columbia Univ, Med Ctr, Div Pediat Pulmonol, Dept Pediat, New York, NY USA.
[Gern, James] Univ Wisconsin, Sch Med, Dept Pediat, Div Allergy & Immunol, Madison, WI 53706 USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Div Allergy & Immunol, Baltimore, MD 21287 USA.
RP Wood, RA (reprint author), Johns Hopkins Univ, Sch Med, 600 North Wolfe St,CMSC 1102, Baltimore, MD 21287 USA.
EM rwood@jhmi.edu
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; Department of Health and Human Services
[NO1-AI-25496, NO1-AI-25482, HHSN2722 00900052C, HHSN272201000052I]
FX Supported in whole or in part with federal funds from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Department of Health and Human Services, under contract nos.
NO1-AI-25496, NO1-AI-25482, HHSN2722 00900052C, and HHSN272201000052I.
Additional support was provided under grants RR00052, M01RR00533,
1UL1RR025771, M01RR00071, 1UL1RR024156, and 5UL1RR024992-02.
NR 37
TC 12
Z9 12
U1 5
U2 27
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2015
VL 135
IS 1
BP 171
EP U261
DI 10.1016/j.jaci.2014.06.033
PG 12
WC Allergy; Immunology
SC Allergy; Immunology
GA AY0PG
UT WOS:000347298200021
PM 25129677
ER
PT J
AU Pino-Yanes, M
Thakur, N
Gignoux, CR
Galanter, JM
Roth, LA
Eng, C
Nishimura, KK
Oh, SS
Vora, H
Huntsman, S
Nguyen, EA
Hu, DL
Drake, KA
Conti, DV
Moreno-Estrada, A
Sandoval, K
Winkler, CA
Borrell, LN
Lurmann, F
Islam, TS
Davis, A
Farber, HJ
Meade, K
Avila, PC
Serebrisky, D
Bibbins-Domingo, K
Lenoir, MA
Ford, JG
Brigino-Buenaventura, E
Rodriguez-Cintron, W
Thyne, SM
Sen, S
Rodriguez-Santana, JR
Bustamante, CD
Williams, LK
Gilliland, FD
Gauderman, WJ
Kumar, R
Torgerson, DG
Burchard, EG
AF Pino-Yanes, Maria
Thakur, Neeta
Gignoux, Christopher R.
Galanter, Joshua M.
Roth, Lindsey A.
Eng, Celeste
Nishimura, Katherine K.
Oh, Sam S.
Vora, Hita
Huntsman, Scott
Nguyen, Elizabeth A.
Hu, Donglei
Drake, Katherine A.
Conti, David V.
Moreno-Estrada, Andres
Sandoval, Karla
Winkler, Cheryl A.
Borrell, Luisa N.
Lurmann, Fred
Islam, Talat S.
Davis, Adam
Farber, Harold J.
Meade, Kelley
Avila, Pedro C.
Serebrisky, Denise
Bibbins-Domingo, Kirsten
Lenoir, Michael A.
Ford, Jean G.
Brigino-Buenaventura, Emerita
Rodriguez-Cintron, William
Thyne, Shannon M.
Sen, Saunak
Rodriguez-Santana, Jose R.
Bustamante, Carlos D.
Williams, L. Keoki
Gilliland, Frank D.
Gauderman, W. James
Kumar, Rajesh
Torgerson, Dara G.
Burchard, Esteban G.
TI Genetic ancestry influences asthma susceptibility and lung function
among Latinos
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PUERTO-RICAN CHILDREN; NATIVE-AMERICAN
ANCESTRY; CHILDHOOD ASTHMA; AFRICAN ANCESTRY; UNITED-STATES;
SOCIOECONOMIC-STATUS; ADMIXED POPULATIONS; LOCAL ANCESTRY; SKIN COLOR
AB Background: Childhood asthma prevalence and morbidity varies among Latinos in the United States, with Puerto Ricans having the highest and Mexicans the lowest.
Objective: To determine whether genetic ancestry is associated with the odds of asthma among Latinos, and secondarily whether genetic ancestry is associated with lung function among Latino children.
Methods: We analyzed 5493 Latinos with and without asthma from3 independent studies. For each participant, we estimated the proportion of African, European, and Native American ancestry using genome-wide data. We tested whether genetic ancestry was associated with the presence of asthma and lung function among subjects with and without asthma. Odds ratios ( OR) and effect sizes were assessed for every 20% increase in each ancestry.
Results: Native American ancestry was associated with lower odds of asthma ( OR 5 0.72, 95% CI: 0.66-0.78, P 5 8.0 3 10 215), while African ancestry was associated with higher odds of asthma ( OR 5 1.40, 95% CI: 1.14-1.72, P 5.001). These associations were robust to adjustment for covariates related to early life exposures, air pollution, and socioeconomic status. Among children with asthma, African ancestry was associated with lower lung function, including both pre-and postbronchodilator measures of FEV1 ( 277 6 19 mL; P 5 5.8 3 10 25 and 283 6 19 mL; P 5 1.1 x 10 25, respectively) and forced vital capacity ( 2100 6 21 mL; P 5 2.7 3 10 26 and 2107 6 22 mL; P 5 1.0 x 10 26, respectively). Conclusion: Differences in the proportions of genetic ancestry can partially explain disparities in asthma susceptibility and lung function among Latinos. ( J Allergy Clin Immunol 2015; 135: 228-35.)
C1 [Pino-Yanes, Maria; Thakur, Neeta; Galanter, Joshua M.; Roth, Lindsey A.; Eng, Celeste; Nishimura, Katherine K.; Oh, Sam S.; Huntsman, Scott; Nguyen, Elizabeth A.; Hu, Donglei; Torgerson, Dara G.; Burchard, Esteban G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Pino-Yanes, Maria; Burchard, Esteban G.] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
[Gignoux, Christopher R.; Galanter, Joshua M.; Drake, Katherine A.; Burchard, Esteban G.] UCSF, Dept Bioengn & Therapeut Sci, San Francisco, CA USA.
[Vora, Hita; Conti, David V.; Islam, Talat S.; Gilliland, Frank D.; Gauderman, W. James] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Moreno-Estrada, Andres; Sandoval, Karla; Bustamante, Carlos D.] Stanford Univ, Dept Genet, Palo Alto, CA 94304 USA.
[Winkler, Cheryl A.] NCI, Basic Res Lab, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21701 USA.
[Borrell, Luisa N.] CUNY, Dept Hlth Sci, Grad Program Publ Hlth, Bronx, NY USA.
[Lurmann, Fred] Sonoma Technol Inc, Petaluma, CA USA.
[Davis, Adam; Meade, Kelley] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA.
[Farber, Harold J.] Baylor Coll Med, Dept Pediat, Sect Pulmonol, Houston, TX 77030 USA.
[Farber, Harold J.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Avila, Pedro C.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA.
[Serebrisky, Denise] Jacobi Med Ctr, Pediat Pulm Div, Bronx, NY USA.
[Bibbins-Domingo, Kirsten] UCSF, Div Gen Internal Med, San Francisco, CA USA.
[Lenoir, Michael A.] Bay Area Pediat, Oakland, CA USA.
[Ford, Jean G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Brigino-Buenaventura, Emerita] Kaiser Permanente Vallejo Med Ctr, Dept Allergy & Immunol, Vallejo, CA USA.
[Rodriguez-Cintron, William] Vet Caribbean Hlth Care Syst, San Juan, PR USA.
[Thyne, Shannon M.] UCSF, San Francisco Gen Hosp, Dept Pediat, San Francisco, CA USA.
[Sen, Saunak] UCSF, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Rodriguez-Santana, Jose R.] Ctr Neumol Pediat, San Juan, PR USA.
[Williams, L. Keoki] Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.
[Williams, L. Keoki] Henry Ford Hlth Syst, Dept Internal Med, Detroit, MI USA.
[Kumar, Rajesh] Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA.
[Kumar, Rajesh] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Pino-Yanes, M (reprint author), Univ Calif San Francisco, Dept Med, 1550 4th St,Rock Hall Room 582,UCSF Box 2911, San Francisco, CA 94143 USA.
EM mdelpino@ull.edu.es
RI Pino-Yanes, Maria/C-8498-2017;
OI Pino-Yanes, Maria/0000-0003-0332-437X; Nguyen,
Elizabeth/0000-0002-8070-6382
FU National Institutes of Health (NIH) [R01-ES015794, U19-AI077439,
R01-HL088133, R01-HL078885, R25-CA113710, T32-GM007546, R01-HL004464,
R01-HL104608, R01AI079139, R01AI061774, P30ES007048, P01ES011627,
R01ES023262, R01ES021801, K23-HL093023]; National Institute
onMinorityHealthAndHealth Disparities [P60MD006902, M01-RR00188];
NationalCancer Institute, National Institutes ofHealth
[HHSN26120080001E]
FX This study was supported in part by National Institutes of Health (NIH)
R01-ES015794, U19-AI077439, R01-HL088133, R01-HL078885, R25-CA113710,
T32-GM007546, R01-HL004464, R01-HL104608 to E. G. B., R01AI079139 and
R01AI061774 to L. K. W., P30ES007048, P01ES011627, R01ES023262,
R01ES021801 to F. G., and K23-HL093023 to R. K.; the National Institute
onMinorityHealthAndHealth Disparities under award number P60MD006902 to
K. B. D and E. G. B. and M01-RR00188 to the Texas Children's Hospital
General Clinical Research Center; Flight Attendant Medical Research
Institute, RWJFAmosMedical FacultyDevelopmentAward, the Sandler
Foundation to E. G. B.; theAmerican Asthma Foundation to L. K. W. and E.
G. B.; Ernest S. BazleyGrant to P. C. A.; and theNationalCancer
Institute, National Institutes ofHealth, under contract HHSN26120080001E
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research to C. A. W. C. R.
G. was supported in part by the UCSF Chancellor's Research Fellowship,
Dissertation Year Fellowship, and National Institutes of Health Training
Grant T32 GM007175. J. M. G. was supported in part by National
Institutes of Health Training Grant T32 (GM007546) and career
development awards from the NHLBI K23 (K23HL111636) and NCATS KL2
(KL2TR000143), aswell as the Hewett Fellowship. M. P. Y. was funded by a
postdoctoral fellowship from Fundaci ~ on Ram ~ on Areces, Madrid,
Spain.
NR 53
TC 18
Z9 18
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD JAN
PY 2015
VL 135
IS 1
BP 228
EP 235
DI 10.1016/j.jaci.2014.07.053
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA AY0PG
UT WOS:000347298200027
PM 25301036
ER
PT J
AU Powell-Wiley, TM
AF Powell-Wiley, Tiffany M.
TI Capsule Commentary on Paul et al., Size Misperception Among Overweight
and Obese Families
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
C1 NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Powell-Wiley, TM (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM Tiffany.powell@nih.gov
FU Intramural NIH HHS
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JAN
PY 2015
VL 30
IS 1
BP 95
EP 95
DI 10.1007/s11606-014-3040-5
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA AY2JG
UT WOS:000347414800019
PM 25277879
ER
PT J
AU Wu, J
Zhang, RH
Tang, N
Gong, ZZ
Zhou, JF
Chen, YW
Chen, K
Cai, W
AF Wu, Jin
Zhang, Ruihua
Tang, Ning
Gong, Zizhen
Zhou, Jiefei
Chen, Yingwei
Chen, Kang
Cai, Wei
TI Dopamine inhibits the function of Gr-1(+)CD115(+) myeloid-derived
suppressor cells through D1-like receptors and enhances anti-tumor
immunity
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE iNOS; nitric oxide; MDSC; neurotransmitter; cancer; immune suppression
ID REGULATORY T-CELLS; TUMOR-BEARING MICE; NITRIC-OXIDE;
PARKINSONS-DISEASE; SIGNALING PATHWAY; CANCER-PATIENTS; INFLAMMATION;
LYMPHOCYTE; ACTIVATION; MECHANISM
AB MDSCs accumulate in tumor-bearing animals and cancer patients and are a major factor responsible for cancer-induced immunosuppression that limits effective cancer immunotherapy. Strategies aimed at effectively inhibiting the function of MDSCs are expected to enhance host anti-tumor immunity and improve cancer immunotherapy significantly. The neurotransmitter DA has been found to have anti-cancer activity, but the underlying mechanism is poorly understood. In this study, we sought to investigate the therapeutic mechanism and efficacy of DA on the inhibition of cancer development via the regulation of MDSC functions. The regulation of the suppressive function of Gr-1(+)CD115(+) MDSCs by DA was determined by use of murine syngeneic LLC and B16 graft models treated with DA in vivo, as well as Gr-1(+)CD115(+) MDSCs isolated from these model treated with DA ex vivo. Here, we show that Gr-1(+)CD115(+) monocytic MDSCs express D1-like DA receptors. DA dramatically attenuated the inhibitory function of tumor-induced monocytic MDSCs on T cell proliferation and IFN-gamma production via D1-like DA receptors and retarded tumor growth. DA and other D1 receptor agonists inhibited IFN-gamma-induced NO production by MDSCs from tumor-bearing mice and cancer patients. Decreased NO production was, in part, mediated via the suppression of p-ERK and p-JNK. In conclusion, the neurotransmitter DA potently inhibits the suppressive function of MDSC and enhances anti-tumor immunity. Our finding provides a mechanistic basis for the use of DA or D1-like receptor agonists to overcome tumor-induced immunosuppression in cancer immunotherapy.
C1 [Wu, Jin; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Cai, Wei] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Inst Pediat Res, Shanghai, Peoples R China.
[Chen, Yingwei] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gastroenterol, Shanghai, Peoples R China.
[Wu, Jin; Tang, Ning; Gong, Zizhen; Zhou, Jiefei; Chen, Yingwei; Cai, Wei] Shanghai Key Lab Pediat Gastroenterol & Nutr, Shanghai, Peoples R China.
[Zhang, Ruihua] Icahn Sch Med Mt Sinai, Dept Med, Inst Immunol, New York, NY 10029 USA.
[Chen, Kang] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Chen, Kang] Wayne State Univ, Dept Immunol & Microbiol, Detroit, MI USA.
[Chen, Kang] Wayne State Univ, Dept Oncol, Detroit, MI USA.
[Chen, Kang] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, US Natl Inst Hlth, Detroit, MI USA.
[Chen, Kang] Barbara Ann Karmanos Canc Inst, Tumor Biol & Microenvironm Program, Detroit, MI USA.
[Chen, Kang] NIAID, Mucosal Immunol Studies Team, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Wu, J (reprint author), Xinhua Hosp, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China.
EM wujin51@yahoo.com; caiw1978@163.com
FU National Natural Science Foundation of China [81201602]; Shanghai
Pujiang Program [12PJ1407600]; Scientific Foundation of Shanghai Health
Bureau [20114138]; Scientific Research Foundation for Returned Scholars
(Ministry of Education of China); Shanghai Key Laboratory of Pediatric
Gastroenterology and Nutrition [11DZ2260500]
FX This work was supported by grants from National Natural Science
Foundation of China (81201602), Shanghai Pujiang Program (12PJ1407600),
Scientific Foundation of Shanghai Health Bureau (20114138), and
Scientific Research Foundation for Returned Scholars (Ministry of
Education of China; to J.W.) and Shanghai Key Laboratory of Pediatric
Gastroenterology and Nutrition (11DZ2260500; to W.C.).
NR 55
TC 6
Z9 8
U1 0
U2 6
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD JAN
PY 2015
VL 97
IS 1
BP 191
EP 200
DI 10.1189/jlb.5A1113-626RR
PG 10
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA AY3CZ
UT WOS:000347463400021
PM 25341727
ER
PT J
AU Lockey, JE
Redlich, CA
Streicher, R
Pfahles-Hutchens, A
Hakkinen, PJ
Ellison, GL
Harber, P
Utell, M
Holland, J
Comai, A
White, M
AF Lockey, James E.
Redlich, Carrie A.
Streicher, Robert
Pfahles-Hutchens, Andrea
Hakkinen, Pertti (Bert) J.
Ellison, Gary L.
Harber, Philip
Utell, Mark
Holland, John
Comai, Andrew
White, Marc
TI Isocyanates and Human Health Multistakeholder Information Needs and
Research Priorities
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID METHYLENE DIPHENYL DIISOCYANATE; COLLISION REPAIR INDUSTRY; OCCUPATIONAL
ASTHMA; TOLUENE DIISOCYANATE; EXPOSURE LIMITS; SKIN EXPOSURE;
POLYURETHANE; SURVEILLANCE
AB Objectives: To outline the knowledge gaps and research priorities identified by a broad base of stakeholders involved in the planning and participation of an international conference and research agenda workshop on isocyanates and human health held in Potomac, Maryland, in April 2013. Methods: A multimodal iterative approach was used for data collection including preconference surveys, review of a 2001 consensus conference on isocyanates, oral and poster presentations, focused break-out sessions, panel discussions, and postconference research agenda workshop. Results: Participants included representatives of consumer and worker health, health professionals, regulatory agencies, academic and industry scientists, labor, and trade associations. Conclusions: Recommendations were summarized regarding knowledge gaps and research priorities in the following areas: worker and consumer exposures; toxicology, animal models, and biomarkers; human cancer risk; environmental exposure and monitoring; and respiratory epidemiology and disease, and occupational health surveillance.
C1 [Lockey, James E.] Univ Cincinnati, Div Occupat & Environm Med, Dept Environm Hlth, Pulm Div,Dept Internal Med,Coll Med, Cincinnati, OH 45267 USA.
[Redlich, Carrie A.] Yale Univ, Sch Med, Yale Occupat & Environm Med, New Haven, CT USA.
[Streicher, Robert] NIOSH, Div Appl Res & Technol, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
[Pfahles-Hutchens, Andrea] US EPA, Risk Assessment Div, Off Chem Safety & Pollut Prevent, Washington, DC 20460 USA.
[Hakkinen, Pertti (Bert) J.] NIH, Off Clin Toxicol, Specialized Informat Serv, Natl Lib Med, Bethesda, MD 20892 USA.
[Ellison, Gary L.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Harber, Philip] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA.
[Utell, Mark] Univ Rochester, Med Ctr, Rochester, NY 14627 USA.
[Holland, John] Holland Associates, Palo Alto, CA USA.
[Comai, Andrew] UAW Hlth & Safety, Int Union, Detroit, MI USA.
[White, Marc] Univ British Columbia, Dept Family Practice, Vancouver, BC V5Z 1M9, Canada.
[White, Marc] Canadian Inst Relief Pain & Disabil, Vancouver, BC, Canada.
RP Lockey, JE (reprint author), Univ Cincinnati, Coll Med, Div Occupat & Environm Med, Dept Environm Hlth, 3223 Eden Ave, Cincinnati, OH 45267 USA.
EM lockeyje@ucmail.uc.edu
RI White, Marc/N-8404-2015; Hakkinen, Pertti/G-4803-2016;
OI Hakkinen, Pertti/0000-0002-8295-9738; White, Marc/0000-0001-7623-1268
FU National Institutes of Health, National Cancer Institute; Canadian
Institutes for Health Research-Institute of Cancer Research; University
of Cincinnati College of Medicine
FX National Institutes of Health, National Cancer Institute; Canadian
Institutes for Health Research-Institute of Cancer Research; and
University of Cincinnati College of Medicine.
NR 30
TC 3
Z9 3
U1 3
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1076-2752
EI 1536-5948
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD JAN
PY 2015
VL 57
IS 1
BP 44
EP 51
DI 10.1097/JOM.0000000000000278
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AY3IP
UT WOS:000347477900010
PM 25563538
ER
PT J
AU Wigton, R
Radua, J
Allen, P
Averbeck, B
Meyer-Lindenberg, A
McGuire, P
Shergill, SS
Fusar-Poli, P
AF Wigton, Rebekah
Radua, Jocham
Allen, Paul
Averbeck, Bruno
Meyer-Lindenberg, Andreas
McGuire, Philip
Shergill, Sukhi S.
Fusar-Poli, Paolo
TI Neurophysiological effects of acute oxytocin administration: systematic
review and meta-analysis of placebo-controlled imaging studies
SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE
LA English
DT Review
ID SOCIAL ANXIETY DISORDER; ASSOCIATIVE LEARNING-TASK; HUMAN BRAIN;
EMOTIONAL FACES; DOPAMINE INTERACTIONS; INTRANASAL OXYTOCIN; AMYGDALA
REACTIVITY; PREFRONTAL CORTEX; INSULA ACTIVATION; NEURAL CIRCUITRY
AB Background: Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. Methods: We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. Results: We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. Limitations: This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. Conclusion: Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration.
C1 [Wigton, Rebekah; Radua, Jocham; Allen, Paul; McGuire, Philip; Shergill, Sukhi S.; Fusar-Poli, Paolo] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London SE5 8AF, England.
[Radua, Jocham] Cibersam, Fidmag, Barcelona, Spain.
[Averbeck, Bruno] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Meyer-Lindenberg, Andreas] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany.
RP Wigton, R (reprint author), Kings Coll London, Inst Psychiat, Cognit & Schizophrenia Imaging Lab, De Crespigny Pk Rd, London SE5 8AF, England.
EM rebekah.wigton@kcl.ac.uk
RI Meyer-Lindenberg, Andreas/H-1076-2011
OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123
FU NARSAD Young Investigator Award
FX P. Fusar-Poli was supported in part by a 2014 NARSAD Young Investigator
Award.
NR 133
TC 23
Z9 23
U1 1
U2 29
PU CMA-CANADIAN MEDICAL ASSOC
PI OTTAWA
PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA
SN 1180-4882
EI 1488-2434
J9 J PSYCHIATR NEUROSCI
JI J. Psychiatry Neurosci.
PD JAN
PY 2015
VL 40
IS 1
BP E1
EP E22
DI 10.1503/jpn.130289
PG 22
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AY4KA
UT WOS:000347545500001
PM 25520163
ER
PT J
AU Starke, C
Betz, H
Hickmann, L
Lachmann, P
Neubauer, B
Kopp, JB
Sequeira-Lopez, MLS
Gomez, RA
Hohenstein, B
Todorov, VT
Hugo, CPM
AF Starke, Charlotte
Betz, Hannah
Hickmann, Linda
Lachmann, Peter
Neubauer, Bjoern
Kopp, Jeffrey B.
Sequeira-Lopez, Maria Luisa S.
Gomez, R. Ariel
Hohenstein, Bernd
Todorov, Vladimir T.
Hugo, Christian P. M.
TI Renin Lineage Cells Repopulate the Glomerular Mesangium after Injury
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID EXPRESSION; MICE; GLOMERULONEPHRITIS; NEPHRITIS; PHENOTYPE
AB Mesangial cell injury has a major role in many CKDs. Because renin-positive precursor cells give rise to mesangial cells during nephrogenesis, this study tested the hypothesis that the same phenomenon contributes to glomerular regeneration after murine experimental mesangial injury. Mesangiolysis was induced by administration of an anti-mesangial cell serum in combination with LPS. In enhanced green fluorescent protein-reportermice with constitutively labeled renin lineage cells, the size of the enhanced green fluorescent protein-positive area in the glomerular tufts increased after mesangial injury. Furthermore, we generated a novel Tet-on inducible triple-transgenic LacZ reporter line that allowed selective labeling of renin cells along renal afferent arterioles of adult mice. Although no intraglomerular LacZ expression was detected in healthy mice, about two-thirds of the glomerular tufts became LacZ positive during the regenerative phase after severe mesangial injury. Intraglomerular renin descendant LacZ-expressing cells colocalized with mesangial cell markers alpha 8-integrin and PDGF receptor-beta but not with endothelial, podocyte, or parietal epithelial cell markers. In contrast with LacZ-positive cells in the afferent arterioles, LacZ-positive cells in the glomerular tuft did not express renin. These data demonstrate that extraglomerular renin lineage cells represent a major source of repopulating cells for reconstitution of the intraglomerular mesangium after injury.
C1 [Starke, Charlotte; Betz, Hannah; Hickmann, Linda; Lachmann, Peter; Hohenstein, Bernd; Todorov, Vladimir T.; Hugo, Christian P. M.] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Div Nephrol, Dept Internal Med 3, D-01307 Dresden, Germany.
[Neubauer, Bjoern] Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
[Sequeira-Lopez, Maria Luisa S.; Gomez, R. Ariel] Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA.
RP Todorov, VT (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Div Nephrol, Dept Internal Med 3, Fetscherstr 74, D-01307 Dresden, Germany.
EM vladimir.todorov@uniklinikum-dresden.de;
christian.hugo@uniklinikum-dresden.de
OI Kopp, Jeffrey/0000-0001-9052-186X
FU German Research Foundation [HU-600/6-1, TO 679/1-1, SFB 699/B1,
HO-2522/6-1]; Intramural Research Program of the National Institutes of
Health National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by grants from the German Research
Foundation(HU-600/6-1 to C.H., TO 679/1-1 and SFB 699/B1 to V.T.T., and
HO-2522/6-1 to B.H.) and the Intramural Research Program of the National
Institutes of Health National Institute of Diabetes and Digestive and
Kidney Diseases (to J.B.K.).
NR 18
TC 14
Z9 14
U1 2
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 JAN
PY 2015
VL 26
IS 1
BP 48
EP 54
DI 10.1681/ASN.2014030265
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AY4QS
UT WOS:000347564000009
PM 24904091
ER
PT J
AU Yoo, TH
Pedigo, CE
Guzman, J
Correa-Medina, M
Wei, CL
Villarreal, R
Mitrofanova, A
Leclercq, F
Faul, C
Li, J
Kretzler, M
Nelson, RG
Lehto, M
Forsblom, C
Groop, PH
Reiser, J
Burke, GW
Fornoni, A
Merscher, S
AF Yoo, Tae-Hyun
Pedigo, Christopher E.
Guzman, Johanna
Correa-Medina, Mayrin
Wei, Changli
Villarreal, Rodrigo
Mitrofanova, Alla
Leclercq, Farah
Faul, Christian
Li, Jing
Kretzler, Matthias
Nelson, Robert G.
Lehto, Markku
Forsblom, Carol
Groop, Per-Henrik
Reiser, Jochen
Burke, George William
Fornoni, Alessia
Merscher, Sandra
TI Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine
Podocyte Injury Phenotypes in Glomerular Disease
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HUMAN DIABETIC-NEPHROPATHY; TNF
RECEPTORS 1; UROKINASE RECEPTOR; KIDNEY-DISEASE; SUPAR LEVELS;
ACTIVATOR; PERMEABILITY; KINASE; CELLS
AB Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte alpha V beta(3) integrin-dependent migration in vitro. Furthermore, alpha V beta(3) integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent alpha V beta(3) integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented alpha V beta(3) integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.
C1 [Yoo, Tae-Hyun; Pedigo, Christopher E.; Guzman, Johanna; Correa-Medina, Mayrin; Villarreal, Rodrigo; Mitrofanova, Alla; Leclercq, Farah; Faul, Christian; Fornoni, Alessia; Merscher, Sandra] Univ Miami, Miller Sch Med, Peggy & Harold Katz Family Drug Discovery Ctr, Dept Med,Div Nephrol & Hypertens, Miami, FL 33136 USA.
[Burke, George William] Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33136 USA.
[Yoo, Tae-Hyun] Yonsei Univ, Coll Med, Div Nephrol, Dept Internal Med, Seoul, South Korea.
[Guzman, Johanna; Fornoni, Alessia; Merscher, Sandra] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA.
[Wei, Changli; Li, Jing; Reiser, Jochen] Rush Univ, Div Nephrol, Dept Internal Med, Chicago, IL 60612 USA.
[Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA.
[Nelson, Robert G.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
[Lehto, Markku; Forsblom, Carol; Groop, Per-Henrik] Biomedicum Helsinki, Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland.
[Lehto, Markku; Forsblom, Carol; Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Dept Med, Div Nephrol, Helsinki, Finland.
[Lehto, Markku; Forsblom, Carol; Groop, Per-Henrik] Univ Helsinki, Diabet & Obes Res Program, Res Programs Unit, Helsinki, Finland.
[Groop, Per-Henrik] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
RP Fornoni, A (reprint author), Univ Miami, Div Nephrol & Hypertens, 1580 NW 10th Ave, Miami, FL 33136 USA.
EM afornoni@med.miami.edu; smerscher@med.miami.edu
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; (University of Miami Clinical and
Translational Science Institute) from the National Center for Advancing
Translational Sciences [1UL-1TR00046]; National Institute on Minority
Health and Health Disparities; Yonsei University College of Medicine
Faculty Research Grant [6-2013-0143]; Wilhelm and Else Stockmann
Foundation; Novo Nordisk Foundation; Folkhalsan Research Foundation;
Nordisk Foundation; Academy of Finland [134379]; National Institutes of
Health [R01-DK089394, R01-DK073495, R01-DK101350, DK090316]; Diabetes
Research Institute Foundation; Nephcure Foundation; Peggy and Harold
Katz Family Foundation; Diabetic Complications Consortium (DiaComp);
Stanley J. Glaser Foundation Research Award
FX This study was supported, in part, by the Intramural Research Program of
the National Institute of Diabetes and Digestive and Kidney Diseases.
Part of this project was supported by Grant 1UL-1TR00046 (University of
Miami Clinical and Translational Science Institute) from the National
Center for Advancing Translational Sciences and the National Institute
on Minority Health and Health Disparities. This study was supported by
Yonsei University College of Medicine Faculty Research Grant 6-2013-0143
(to T.-H.Y.) for 2013. The study was also supported by the Wilhelm and
Else Stockmann Foundation (M.L. and P.-H.G.), the Novo Nordisk
Foundation (M.L. and P.-H.G.), the Folkhalsan Research Foundation
(P.-H.G.), and Academy of Finland Grant 134379 (to P.-H.G.). J.R. is
supported by National Institutes of Health Grants R01-DK089394,
R01-DK073495, and R01-DK101350. G.W.B., A.F., and S.M. are supported by
National Institutes of Health Grant DK090316. A.F. and S.M. are
supported by the Diabetes Research Institute Foundation, the Nephcure
Foundation, the Peggy and Harold Katz Family Foundation, and the
Diabetic Complications Consortium (DiaComp). S.M. is supported by a
Stanley J. Glaser Foundation Research Award.
NR 46
TC 20
Z9 22
U1 2
U2 7
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 JAN
PY 2015
VL 26
IS 1
BP 133
EP 147
DI 10.1681/ASN.2013111213
PG 15
WC Urology & Nephrology
SC Urology & Nephrology
GA AY4QS
UT WOS:000347564000016
PM 24925721
ER
PT J
AU Rebholz, CM
Grams, ME
Coresh, J
Selvin, E
Inker, LA
Levey, AS
Kimmel, PL
Vasan, RS
Eckfeldt, JH
Feldman, HI
Hsu, CY
Lutsey, PL
AF Rebholz, Casey M.
Grams, Morgan E.
Coresh, Josef
Selvin, Elizabeth
Inker, Lesley A.
Levey, Andrew S.
Kimmel, Paul L.
Vasan, Ramachandran S.
Eckfeldt, John H.
Feldman, Harold I.
Hsu, Chi-yuan
Lutsey, Pamela L.
CA Chronic Kidney Dis Biomarkers
TI Serum Fibroblast Growth Factor-23 Is Associated with Incident Kidney
Disease
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; PARATHYROID-HORMONE;
PROGRESSION; MORTALITY; FGF23; RISK; PHOSPHATE; HEART;
FIBROBLAST-GROWTH-FACTOR-23
AB Fibroblast growth factor-23 is a bone-derived hormone that increases urinary phosphate excretion and inhibits hydroxylation of 25-hydroxyvitamin D. Recent studies suggest that fibroblast growth factor-23 may be an early biomarker of CKD progression. However, its role in kidney function decline in the general population is unknown. We assessed the relationship between baseline (1990-1992) serum levels of intact fibroblast growth factor-23 and incident ESRD in 13,448 Atherosclerosis Risk in Communities study participants (56.1% women, 74.7% white) followed until December 31, 2010. At baseline, the mean age of participants was 56.9 years and the mean eGFR was 97 ml/min per 1.73m(2). During a median follow-up of 19 years, 267 participants (2.0%) developed ESRD. After adjustment for demographic characteristics, baseline eGFR, traditional CKD risk factors, and markers of mineral metabolism, the highest fibroblast growth factor-23 quintile (>54.6 pg/ml) compared with the lowest quintile (<32.0 pg/ml) was associated with risk of developing ESRD (hazard ratio, 2.10; 95% confidence interval, 1.31 to 3.36; trend P<0.001). In a large, community-based study comprising a broad range of kidney function, higher baseline fibroblast growth factor-23 levels were associated with increased risk of incident ESRD independent of the baseline level of kidney function and a number of other risk factors.
C1 [Rebholz, Casey M.; Grams, Morgan E.; Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Rebholz, Casey M.; Grams, Morgan E.; Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA.
[Grams, Morgan E.] Johns Hopkins Sch Med, Div Nephrol, Dept Med, Baltimore, MD USA.
[Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Sch Med, Div Gen Internal Med, Dept Med, Baltimore, MD USA.
[Inker, Lesley A.; Levey, Andrew S.] Tufts Med Ctr, Dept Med, William B Schwartz Div Nephrol, Boston, MA USA.
[Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med & Epidemiol & Cardiol, Boston, MA 02118 USA.
[Eckfeldt, John H.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Feldman, Harold I.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Feldman, Harold I.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Hsu, Chi-yuan] Univ Calif San Francisco, Sch Med, Dept Med, Div Nephrol, San Francisco, CA USA.
[Lutsey, Pamela L.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Rebholz, CM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 2024 E Monument St,Suite 2-600, Baltimore, MD 21287 USA.
EM crebhol1@jhu.edu
OI Grams, Morgan/0000-0002-4430-6023; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; NHLBI [R01-HL103706, T32-HL007024]; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[R01-DK089174]; NIDDK [U01-DK085649, U01-DK085673, U01-DK085660,
U01-DK085688, U01-DK085651, U01-DK085689]
FX The ARIC study is conducted as a collaborative study supported by
contracts from the National Heart, Lung, and Blood Institute (NHLBI)
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, and HHSN268201100012C). Measurement of the main
analytes in this article was supported by grants from the NHLBI
(R01-HL103706 to P.L.) and the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) (R01-DK089174 to E.S.). C.M.R. is
supported in part by an NHLBI cardiovascular epidemiology training grant
(T32-HL007024). This study was partially supported by grants from the
NIDDK (U01-DK085649, U01-DK085673, U01-DK085660, U01-DK085688,
U01-DK085651, and U01-DK085689 to the Chronic Kidney Disease Biomarkers
Consortium).
NR 42
TC 13
Z9 13
U1 1
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 JAN
PY 2015
VL 26
IS 1
BP 192
EP 200
DI 10.1681/ASN.2014020218
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA AY4QS
UT WOS:000347564000021
PM 25060052
ER
PT J
AU Cuburu, N
Wang, KN
Goodman, KN
Pang, YY
Thompson, CD
Lowy, DR
Cohen, JI
Schiller, JT
AF Cuburu, Nicolas
Wang, Kening
Goodman, Kyle N.
Pang, Yuk Ying
Thompson, Cynthia D.
Lowy, Douglas R.
Cohen, Jeffrey I.
Schiller, John T.
TI Topical Herpes Simplex Virus 2 (HSV-2) Vaccination with Human
Papillomavirus Vectors Expressing gB/gD Ectodomains Induces
Genital-Tissue-Resident Memory CD8(+) T Cells and Reduces Genital
Disease and Viral Shedding after HSV-2 Challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PLASMID DNA VACCINE; IMMUNE-RESPONSES; GLYCOPROTEIN-B; GUINEA-PIGS;
INTRANASAL IMMUNIZATION; PROTECTIVE IMMUNITY; TYPE-2 INFECTION; SENSORY
GANGLIA; SUBUNIT VACCINE; DENDRITIC CELLS
AB No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection.
IMPORTANCE
Genital herpes is a highly prevalent chronic disease caused by HSV infection. To date, there is no licensed vaccine against HSV infection. This study describes intravaginal vaccination with a nonreplicating HPV-based vector expressing HSV glycoprotein antigens. The data presented in this study underscore the potential of HPV-based vectors as a platform for the induction of genital-tissue-resident memory T cell responses and the control of local manifestations of primary HSV infection.
C1 [Cuburu, Nicolas; Pang, Yuk Ying; Thompson, Cynthia D.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Kening; Goodman, Kyle N.; Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
EM schillej@dc37a.nci.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Cancer
Institute, Center for Cancer Research, NIH
FX This work was supported by the intramural research programs of the
National Institute of Allergy and Infectious Diseases and the National
Cancer Institute, Center for Cancer Research, NIH.
NR 66
TC 5
Z9 5
U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JAN
PY 2015
VL 89
IS 1
BP 83
EP 96
DI 10.1128/JVI.02380-14
PG 14
WC Virology
SC Virology
GA AX8RL
UT WOS:000347176100008
PM 25320297
ER
PT J
AU Weiskopf, D
Angelo, MA
Bangs, DJ
Sidney, J
Paul, S
Peters, B
de Silva, AD
Lindow, JC
Diehl, SA
Whitehead, S
Durbin, A
Kirkpatrick, B
Sette, A
AF Weiskopf, Daniela
Angelo, Michael A.
Bangs, Derek J.
Sidney, John
Paul, Sinu
Peters, Bjoern
de Silva, Aruna D.
Lindow, Janet C.
Diehl, Sean A.
Whitehead, Stephen
Durbin, Anna
Kirkpatrick, Beth
Sette, Alessandro
TI The Human CD8(+) T Cell Responses Induced by a Live Attenuated
Tetravalent Dengue Vaccine Are Directed against Highly Conserved
Epitopes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ANTIGEN PRESENTATION; CLASS-I; VIRUS; INFLUENZA; INFECTION; SEROTYPE;
TRIAL
AB The incidence of infection with any of the four dengue virus serotypes (DENV1 to -4) has increased dramatically in the last few decades, and the lack of a treatment or vaccine has contributed to significant morbidity and mortality worldwide. A recent comprehensive analysis of the human T cell response against wild-type DENV suggested an human lymphocyte antigen (HLA)linked protective role for CD8(+) T cells. We have collected one-unit blood donations from study participants receiving the monovalent or tetravalent live attenuated DENV vaccine (DLAV), developed by the U.S. National Institutes of Health. Peripheral blood mononuclear cells from these donors were screened in gamma interferon enzyme-linked immunosorbent spot assays with pools of predicted, HLA-matched, class I binding peptides covering the entire DENV proteome. Here, we characterize for the first time CD8(+) T cell responses after live attenuated dengue vaccination and show that CD8(+) T cell responses in vaccinees were readily detectable and comparable to natural dengue infection. Interestingly, whereas broad responses to structural and nonstructural (NS) proteins were observed after monovalent vaccination, T cell responses following tetravalent vaccination were, dramatically, focused toward the highly conserved NS proteins. Epitopes were highly conserved in a vast variety of field isolates and able to elicit multifunctional T cell responses. Detailed knowledge of the T cell response will contribute to the identification of robust correlates of protection in natural immunity and following vaccination against DENV.
IMPORTANCE The development of effective vaccination strategies against dengue virus (DENV) infection and clinically significant disease is a task of high global public health value and significance, while also being a challenge of significant complexity. A recent efficacy trial of the most advanced dengue vaccine candidate, demonstrated only partial protection against all four DENV serotypes, despite three subsequent immunizations and detection of measurable neutralizing antibodies to each serotype in most subjects. These results challenge the hypothesis that seroconversion is the only reliable correlate of protection. Here, we show that CD8(+) T cell responses in vaccinees were readily detectable and comparable to natural dengue virus infection. Detailed knowledge of the T cell response may further contribute to the identification of robust correlates of protection in natural immunity and vaccination against DENV.
C1 [Weiskopf, Daniela; Angelo, Michael A.; Bangs, Derek J.; Sidney, John; Paul, Sinu; Peters, Bjoern; de Silva, Aruna D.; Sette, Alessandro] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
[Lindow, Janet C.; Diehl, Sean A.; Kirkpatrick, Beth] Univ Vermont, Coll Med, Burlington, VT USA.
[Lindow, Janet C.; Diehl, Sean A.; Kirkpatrick, Beth] Univ Vermont, Vaccine Testing Ctr, Burlington, VT USA.
[Whitehead, Stephen] NIAID, NIH, Bethesda, MD 20892 USA.
[Durbin, Anna] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[de Silva, Aruna D.] Genetech Res Inst, Colombo, Sri Lanka.
RP Weiskopf, D (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
EM daniela@liai.org
OI Diehl, Sean/0000-0001-9700-235X; Lindow, Janet/0000-0003-3235-3698
FU National Institutes of Health [HHSN272200900042C, HHSN27220140045C]; NIH
National Institute of Allergy and Infectious Diseases
FX This study was supported by National Institutes of Health contracts
HHSN272200900042C and HHSN27220140045C (to A.S.) and in part by the
Intramural Research Program of the NIH National Institute of Allergy and
Infectious Diseases. The hinders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 28
TC 22
Z9 22
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JAN
PY 2015
VL 89
IS 1
BP 120
EP 128
DI 10.1128/JVI.02129-14
PG 9
WC Virology
SC Virology
GA AX8RL
UT WOS:000347176100011
PM 25320311
ER
PT J
AU Kurup, D
Wirblich, C
Feldmann, H
Marzi, A
Schnell, MJ
AF Kurup, Drishya
Wirblich, Christoph
Feldmann, Heinz
Marzi, Andrea
Schnell, Matthias J.
TI Rhabdovirus-Based Vaccine Platforms against Henipaviruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VESICULAR STOMATITIS-VIRUS; RECOMBINANT RABIES VIRUS; NIPAH-VIRUS;
HENDRA-VIRUS; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; ENVELOPE
PROTEINS; G-GLYCOPROTEIN; SARS-COV; PROTECTION
AB The emerging zoonotic pathogens Hendra virus (HeV) and Nipah virus (NiV) are in the genus Henipavirus in the family Paramyxoviridae. HeV and NiV infections can be highly fatal to humans and livestock. The goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (RABV) and recombinant vesicular stomatitis virus (VSV), expressing either the codon-optimized or the wild-type (wt) HeV glycoprotein (G) gene. The RABV vector expressing the codon-optimized HeV G showed a 2- to 3-fold increase in incorporation compared to the RABV vector expressing wt HeV G. There was no significant difference in HeV G incorporation in the VSV vectors expressing either wt or codon-optimized HeV G. Mice inoculated intranasally with any of these live recombinant viruses showed no signs of disease, including weight loss, indicating that HeV G expression and incorporation did not increase the neurotropism of the vaccine vectors. To test the immunogenicity of the vaccine candidates, we immunized mice intramuscularly with either one dose of the live vaccines or 3 doses of 10 mu g chemically inactivated viral particles. Increased codon-optimized HeV G incorporation into RABV virions resulted in higher antibody titers against HeV G compared to inactivated RABV virions expressing wt HeV G. The live VSV vectors induced more HeV G-specific antibodies as well as higher levels of HeV neutralizing antibodies than the RABV vectors. In the case of killed particles, HeV neutralizing serum titers were very similar between the two platforms. These results indicated that killed RABV with codon-optimized HeV G should be the vector of choice as a dual vaccine in areas where rabies is endemic.
IMPORTANCE Scientists have been tracking two new viruses carried by the Pteropid fruit bats: Hendra virus (HeV) and Nipah virus (NiV). Both viruses can be fatal to humans and also pose a serious risk to domestic animals. A recent escalation in the frequency of outbreaks has increased the need for a vaccine that prevents HeV and NiV infections. In this study, we performed an extensive comparison of live and killed particles of two recombinant rhabdoviral vectors, rabies virus and vesicular stomatitis virus (VSV), expressing wild-type or codon-optimized HeV glycoprotein, with the goal of developing a candidate vaccine against HeV. Based on our data from the presented mouse immunogenicity studies, we conclude that a killed RABV vaccine would be highly effective against HeV infections and would make an excellent vaccine candidate in areas where both RABV and henipaviruses pose a threat to human health.
C1 [Kurup, Drishya; Wirblich, Christoph; Schnell, Matthias J.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA.
[Feldmann, Heinz; Marzi, Andrea] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Schnell, Matthias J.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Jefferson Vaccine Ctr, Philadelphia, PA 19107 USA.
RP Schnell, MJ (reprint author), Thomas Jefferson Univ, Sidney Kimmel Med Coll, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA.
EM Matthias.Schnell@jefferson.edu
FU NIAID Division of Intramural Research, NIAID [R01AI105204]; Jefferson
Vaccine Center
FX This work was supported in part by the NIAID Division of Intramural
Research, NIAID grant R01AI105204 to M.J.S., and the Jefferson Vaccine
Center.
NR 63
TC 12
Z9 12
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JAN
PY 2015
VL 89
IS 1
BP 144
EP 154
DI 10.1128/JVI.02308-14
PG 11
WC Virology
SC Virology
GA AX8RL
UT WOS:000347176100013
PM 25320306
ER
PT J
AU Matsuno, K
Weisend, C
Kajihara, M
Matysiak, C
Williamson, BN
Simuunza, M
Mweene, AS
Takada, A
Tesh, RB
Ebihara, H
AF Matsuno, Keita
Weisend, Carla
Kajihara, Masahiro
Matysiak, Colette
Williamson, Brandi N.
Simuunza, Martin
Mweene, Aaron S.
Takada, Ayato
Tesh, Robert B.
Ebihara, Hideki
TI Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to
the Retrospective Identification of Taxonomically Unassigned
Bunyaviruses and the Discovery of a Novel Member of the Genus
Phlebovirus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID THROMBOCYTOPENIA SYNDROME VIRUS; TO-PERSON TRANSMISSION; SEVERE FEVER;
BHANJA VIRUS; GENETIC-CHARACTERIZATION; SEROLOGICAL SURVEY; HEARTLAND
VIRUS; CHINA; ANT